TY - JOUR T1 - Thyroid hormone receptor mutations in cancer. AN - 71568564; 15062571 AB - The thyroid hormone receptors (TRs) mediate the pleiotropic activities of the thyroid hormone (T3) in growth, development, and differentiation and in maintaining metabolic homeostasis. They are ligand-dependent transcription factors and are members of the steroid hormone/retionic acid receptor superfamily. Two TR genes, alpha and beta, located on human chromosomes 17 and 3, respectively, have been identified. That they are cellular homologs of the retroviral v-erbA oncogene suggests their possible involvement in carcinogenesis. Recent studies showed altered expression of TRs at both the mRNA and protein levels and identified somatic mutations of TRs in several human cancers. Furthermore, male transgenic mice overexpressing v-erbA oncogene develop hepatocellular carcinoma. Importantly, a targeted germline mutation of the TRbeta gene leads to the occurrence of metastatic thyroid carcinoma in homozygous mutant mice. These findings provide evidence to support the critical role of TRs in human cancer. JF - Molecular and cellular endocrinology AU - Cheng, Sheue-Yann AD - Gene Regulation Section, Center for Cancer Research, Building 37, Room 5128, 37 Convent Drive MSC 4264, National Cancer Institute, Bethesda, MD 20892-4264, USA. sycheng@helix.nih.gov Y1 - 2003/12/31/ PY - 2003 DA - 2003 Dec 31 SP - 23 EP - 30 VL - 213 IS - 1 SN - 0303-7207, 0303-7207 KW - Receptors, Thyroid Hormone KW - 0 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Humans KW - Signal Transduction KW - Neoplasms -- pathology KW - Receptors, Thyroid Hormone -- genetics KW - Mutation KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71568564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+endocrinology&rft.atitle=Thyroid+hormone+receptor+mutations+in+cancer.&rft.au=Cheng%2C+Sheue-Yann&rft.aulast=Cheng&rft.aufirst=Sheue-Yann&rft.date=2003-12-31&rft.volume=213&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+endocrinology&rft.issn=03037207&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-14 N1 - Date created - 2004-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Cyanovirin-N - An anti-HIV protein with a new twist AN - 39770900; 3815988 AU - Wlodawer, A Y1 - 2003/12/31/ PY - 2003 DA - 2003 Dec 31 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39770900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Cyanovirin-N+-+An+anti-HIV+protein+with+a+new+twist&rft.au=Wlodawer%2C+A&rft.aulast=Wlodawer&rft.aufirst=A&rft.date=2003-12-31&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: South African Crystallography and Structural Chemistry Groups, URL: www.sacrs.org.za/ecm21/ N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Making connections: the development of mesencephalic dopaminergic neurons. AN - 71516757; 14741747 AB - The disorders of two adjacent sets of mesencephalic dopaminergic (MDNs) are associated with two significant health problems: Parkinson's disease and drug addiction. Because of this, a great deal of research has focused on understanding the growth, development and maintenance of MDNs. Many transcription factors and signaling pathways are known to be required for normal MDNs formation, but a unified model of MDN development is still unclear. The long-term goal is to design therapeutic strategies to: (i) nurture and/or heal endogenous MDNs, (ii) replace the affected tissue with exogenous MDNs from in vitro cultivated stem cells and (iii) restore normal connectivity. Recent developmental biology studies show great promise in understanding how MDNs develop both in vivo and in vitro. This information has great therapeutic value and may provide insight into how environmental and genetic factors increase vulnerability to addiction. JF - Brain research. Developmental brain research AU - Riddle, Robert AU - Pollock, Jonathan D AD - Genetics and Molecular Neurobiology Research Branch, Division of Neuroscience and Behavioral Research, National Institute on Drug Abuse, 6001 Executive Blvd., Bethesda, MD 20892-9555, USA. riddler@nida.nih.gov Y1 - 2003/12/30/ PY - 2003 DA - 2003 Dec 30 SP - 3 EP - 21 VL - 147 IS - 1-2 SN - 0165-3806, 0165-3806 KW - Transcription Factors KW - 0 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Substance-Related Disorders -- pathology KW - Humans KW - Neural Pathways -- growth & development KW - Neural Pathways -- embryology KW - Nervous System Diseases -- pathology KW - Zebrafish KW - Neural Pathways -- cytology KW - Female KW - Pregnancy KW - Neurons -- physiology KW - Dopamine -- physiology KW - Mesencephalon -- embryology KW - Mesencephalon -- growth & development KW - Mesencephalon -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71516757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Developmental+brain+research&rft.atitle=Making+connections%3A+the+development+of+mesencephalic+dopaminergic+neurons.&rft.au=Riddle%2C+Robert%3BPollock%2C+Jonathan+D&rft.aulast=Riddle&rft.aufirst=Robert&rft.date=2003-12-30&rft.volume=147&rft.issue=1-2&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Developmental+brain+research&rft.issn=01653806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-03 N1 - Date created - 2004-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methamphetamine-induced gene expression profiles in the striatum of male rat pups exposed to the drug in utero AN - 18041384; 5897260 AB - Methamphetamine is a neurotoxic pychostimulant which affects monoaminergic and non-monoaminergic systems in the brain. Clinical studies in humans have found that exposure to methamphetamine in the developing embryo can cause significant behavioral and cognitive anomalies later in life. Exposure of animals to methamphetamine (METH) in utero can cause neurobehavioral effects that do not become apparent until young adulthood. In the present study, we sought to determine the effects of in utero METH exposure on the striata of perinatal rat pups using a recently developed 17 k cDNA microarray. We found that METH administration caused alterations in 913 genes according to strict criteria. These alterations include changes in genes that participate in signal transduction, heat shock responses and neuronal development. The majority of the changes in gene expression were more prominent at the 7-day time point. These observations suggest that in utero METH exposure might initiate molecular programs that significantly impact gene expression during the developmental period long after the last exposure to this drug. Thus, during development, METH exposure in utero might cause significant long-term changes in gene expression that might constitute, in part, some of the substrates for the behavioral and cognitive anomalies reported in the literature. JF - Developmental Brain Research AU - Noailles, PH AU - Becker, K G AU - Wood, WH III AU - Teichberg, D AU - Cadet, J AD - Molecular Neuropsychiatry Branch, NIDA/NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, JCADET@intra.nida.nih.gov Y1 - 2003/12/30/ PY - 2003 DA - 2003 Dec 30 SP - 153 EP - 162 VL - 147 IS - 1-2 SN - 0165-3806, 0165-3806 KW - rats KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - Intrauterine exposure KW - DNA microarrays KW - Gene expression KW - Methamphetamine KW - Cognitive ability KW - Neostriatum KW - Neurotoxicity KW - Signal transduction KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18041384?accountid=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=Developmental+Brain+Research&rft.atitle=Methamphetamine-induced+gene+expression+profiles+in+the+striatum+of+male+rat+pups+exposed+to+the+drug+in+utero&rft.au=Noailles%2C+PH%3BBecker%2C+K+G%3BWood%2C+WH+III%3BTeichberg%2C+D%3BCadet%2C+J&rft.aulast=Noailles&rft.aufirst=PH&rft.date=2003-12-30&rft.volume=147&rft.issue=1-2&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Developmental+Brain+Research&rft.issn=01653806&rft_id=info:doi/10.1016%2Fj.devbrainres.2003.11.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene expression; Methamphetamine; Intrauterine exposure; Cognitive ability; Neurotoxicity; DNA microarrays; Signal transduction; Neostriatum DO - http://dx.doi.org/10.1016/j.devbrainres.2003.11.003 ER - TY - JOUR T1 - Interaction of 14-3-3 proteins with the insulin-like growth factor I receptor (IGFIR): evidence for a role of 14-3-3 proteins in IGFIR signaling. AN - 71413244; 14651979 AB - We have extended our previous yeast two-hybrid findings to show that 14-3-3beta also interacts with the insulin-like growth factor I receptor (IGFIR) in mammalian cells overexpressing both proteins and that the interaction involves serine 1283 and is dependent on receptor activation. Treatment of cells with the phorbol ester PMA stimulates the interaction of 14-3-3beta with the IGFIR in the absence of receptor tyrosine phosphorylation, suggesting that receptor activation leads to activation of an endogenous protein kinase that catalyzes the phosphorylation of serine 1283. To investigate the role of 14-3-3 proteins in IGF signal transduction, IGFIR structure-function studies were performed. Mutation of serine 1283 alone (S1283A) (a mutation that decreases but does not abolish the interaction of the IGFIR with 14-3-3) did not affect anchorage-independent growth of NIH 3T3 fibroblasts overexpressing the mutant receptor. However, the simultaneous mutation of this residue and the truncation of the C-terminal 27 residues of the receptor (Delta1310/S1283A) abolished the interaction of the receptor with 14-3-3 and reversed the enhanced colony formation observed with the IGFIR truncation mutation alone (Delta1310). The difference between the Delta1310 and Delta1310/S1283A transfectants in the soft agar assay was confirmed by tumorigenesis experiments. These findings suggest that 14-3-3 proteins interact with the IGFIR in vivo and that this interaction may play a role in a transformation pathway signaled by the IGFIR. JF - Biochemical and biophysical research communications AU - Spence, Susan L AU - Dey, Bhakta R AU - Terry, Cheryl AU - Albert, Paul AU - Nissley, Peter AU - Furlanetto, Richard W AD - Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/12/26/ PY - 2003 DA - 2003 Dec 26 SP - 1060 EP - 1066 VL - 312 IS - 4 SN - 0006-291X, 0006-291X KW - 14-3-3 Proteins KW - 0 KW - Recombinant Proteins KW - YWHAB protein, human KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- metabolism KW - Humans KW - Cercopithecus aethiops KW - Carcinogenicity Tests KW - COS Cells -- cytology KW - Mice KW - Mutation KW - Structure-Activity Relationship KW - NIH 3T3 Cells -- cytology KW - Signal Transduction -- physiology KW - Tyrosine 3-Monooxygenase -- metabolism KW - Receptor, IGF Type 1 -- metabolism KW - Cell Division -- physiology KW - Tetradecanoylphorbol Acetate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71413244?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interaction+of+14-3-3+proteins+with+the+insulin-like+growth+factor+I+receptor+%28IGFIR%29%3A+evidence+for+a+role+of+14-3-3+proteins+in+IGFIR+signaling.&rft.au=Spence%2C+Susan+L%3BDey%2C+Bhakta+R%3BTerry%2C+Cheryl%3BAlbert%2C+Paul%3BNissley%2C+Peter%3BFurlanetto%2C+Richard+W&rft.aulast=Spence&rft.aufirst=Susan&rft.date=2003-12-26&rft.volume=312&rft.issue=4&rft.spage=1060&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 - 2004-03-18 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo oligomerization and raft localization of Ebola virus protein VP40 during vesicular budding. AN - 71482593; 14673115 AB - The matrix protein VP40 plays a critical role in Ebola virus assembly and budding, a process that utilizes specialized membrane domains known as lipid rafts. Previous studies with purified protein suggest a role for oligomerization of VP40 in this process. Here, we demonstrate VP40 oligomers in lipid rafts of mammalian cells, virus-like particles, and in the authentic Ebola virus. By mutagenesis, we identify several critical C-terminal sequences that regulate oligomerization at the plasma membrane, association with detergent-resistant membranes, and vesicular release of VP40, directly linking these phenomena. Furthermore, we demonstrate the active recruitment of TSG101 into lipid rafts by VP40. We also report the successful application of the biarsenic fluorophore, FlAsH, combined with a tetracysteine tag for imaging of Ebola VP40 in live cells. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Panchal, Rekha G AU - Ruthel, Gordon AU - Kenny, Tara A AU - Kallstrom, George H AU - Lane, Douglas AU - Badie, Shirin S AU - Li, Limin AU - Bavari, Sina AU - Aman, M Javad AD - Developmental Therapeutics Program, Target Structure Based Drug Discovery Group, Science Applications International Corporation, National Cancer Institute, Frederick, MD 21702-1201, USA. Y1 - 2003/12/23/ PY - 2003 DA - 2003 Dec 23 SP - 15936 EP - 15941 VL - 100 IS - 26 SN - 0027-8424, 0027-8424 KW - Nucleoproteins KW - 0 KW - Recombinant Proteins KW - Viral Core Proteins KW - nucleoprotein VP40, Ebola virus KW - Index Medicus KW - Microscopy, Confocal KW - Cell Membrane -- virology KW - Transfection KW - Humans KW - Kidney KW - Ebolavirus -- genetics KW - Recombinant Proteins -- analysis KW - Cell Line KW - Nucleoproteins -- analysis KW - Nucleoproteins -- genetics KW - Viral Core Proteins -- genetics KW - Viral Core Proteins -- analysis KW - Membrane Microdomains -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71482593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+oligomerization+and+raft+localization+of+Ebola+virus+protein+VP40+during+vesicular+budding.&rft.au=Panchal%2C+Rekha+G%3BRuthel%2C+Gordon%3BKenny%2C+Tara+A%3BKallstrom%2C+George+H%3BLane%2C+Douglas%3BBadie%2C+Shirin+S%3BLi%2C+Limin%3BBavari%2C+Sina%3BAman%2C+M+Javad&rft.aulast=Panchal&rft.aufirst=Rekha&rft.date=2003-12-23&rft.volume=100&rft.issue=26&rft.spage=15936&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 - 2004-04-20 N1 - Date created - 2003-12-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 2002 Apr 19;296(5567):503-7 [11964472] Curr Top Microbiol Immunol. 1999;235:1-21 [9893375] Trends Cell Biol. 2002 Dec;12(12):569-79 [12495845] J Virol. 2003 Feb;77(3):1812-9 [12525615] Structure. 2003 Apr;11(4):423-33 [12679020] Microbes Infect. 2003 Jun;5(7):639-49 [12787740] Cell. 1996 May 3;85(3):319-29 [8616888] Virus Res. 1995 Dec;39(2-3):129-50 [8837880] Adv Virus Res. 1996;47:1-52 [8895830] Cell Signal. 1997 Sep;9(6):395-401 [9376220] Science. 1998 Jul 10;281(5374):269-72 [9657724] Microbiol Mol Biol Rev. 1998 Dec;62(4):1171-90 [9841669] Nat Cell Biol. 1999 Jun;1(2):119-24 [10559884] J Virol. 2000 Apr;74(7):3264-72 [10708443] Science. 2000 Jun 2;288(5471):1647-50 [10834844] J Biol Chem. 2000 Jun 9;275(23):17221-4 [10770957] J Mol Biol. 2000 Jun 30;300(1):103-12 [10864502] Mol Biol Cell. 2000 Aug;11(8):2775-91 [10930469] EMBO J. 2000 Aug 15;19(16):4228-36 [10944105] Methods Enzymol. 2000;327:565-78 [11045009] EMBO J. 2000 Dec 15;19(24):6732-41 [11118208] J Virol. 2001 Jun;75(11):5205-14 [11333902] Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9 [11413487] J Clin Virol. 2001 Oct;22(3):217-27 [11564586] Nat Med. 2001 Dec;7(12):1313-9 [11726971] J Biol Chem. 2001 Dec 7;276(49):46371-8 [11571279] J Exp Med. 2002 Mar 4;195(5):593-602 [11877482] J Biol Chem. 1999 Jan 22;274(4):2038-44 [9890962] J Virol. 2002 May;76(10):4679-87 [11967285] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced levels of lambda Red-mediated recombinants in mismatch repair mutants AN - 19265404; 5831585 AB - Homologous recombination can be used to generate recombinants on episomes or directly on the Escherichia coli chromosome with PCR products or synthetic single-stranded DNA (ssDNA) oligonucleotides (oligos). Such recombination is possible because bacteriophage lambda -encoded functions, called Red, efficiently recombine linear DNA with homologies as short as 20-70 bases. This technology, termed recombineering, provides ways to modify genes and segments of the chromosome as well as to study homologous recombination mechanisms. The Red Beta function, which binds and anneals ssDNA to complementary ssDNA, is able to recombine 70-base oligos with the chromosome. In E. coli, methyl-directed mismatch repair (MMR) can affect these ssDNA recombination events by eliminating the recombinant allele and restoring the original sequence. In so doing, MMR can reduce the apparent recombination frequency by >100-fold. In the absence of MMR, Red-mediated oligo recombination can incorporate a single base change into the chromosome in an unprecedented 25% of cells surviving electroporation. Our results show that Beta is the only bacteriophage function required for this level of recombination and suggest that Beta directs the ssDNA to the replication fork as it passes the target sequence. JF - Proceedings of the National Academy of Sciences, USA AU - Costantino, N AU - Court, D L AD - Molecular Control and Genetics Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, Building 539, P.O. Box B, Frederick, MD 21702-1201, court@ncifcrf.gov Y1 - 2003/12/23/ PY - 2003 DA - 2003 Dec 23 SP - 15748 EP - 15753 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 26 SN - 0027-8424, 0027-8424 KW - mismatch repair KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Phage l KW - Mutants KW - Recombination KW - Alleles KW - Chromosomes KW - Escherichia coli KW - Replication KW - Phage ^l KW - G 07312:Phages KW - J 02750:Phage-host interactions KW - N 14652:DNA repair KW - V 22070:Phage-host interactions including lysogeny & transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19265404?accountid=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=Enhanced+levels+of+lambda+Red-mediated+recombinants+in+mismatch+repair+mutants&rft.au=Costantino%2C+N%3BCourt%2C+D+L&rft.aulast=Costantino&rft.aufirst=N&rft.date=2003-12-23&rft.volume=100&rft.issue=26&rft.spage=15748&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.2434959100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Phage ^l; Phage l; Chromosomes; Mutants; Alleles; Recombination; Replication DO - http://dx.doi.org/10.1073/pnas.2434959100 ER - TY - JOUR T1 - Transcriptome analysis of chlamydial growth during IFN- gamma -mediated persistence and reactivation AN - 19260197; 5831565 AB - Chlamydia trachomatis is an obligatory intracellular prokaryotic parasite that causes a spectrum of clinically important chronic inflammatory diseases of humans. Persistent infection may play a role in the pathophysiology of chlamydial disease. Here we describe the chlamydial transcriptome in an in vitro model of IFN- gamma -mediated persistence and reactivation from persistence. Tryptophan utilization, DNA repair and recombination, phospholipid utilization, protein translation, and general stress genes were up-regulated during persistence. Down-regulated genes included chlamydial late genes and genes involved in proteolysis, peptide transport, and cell division. Persistence was characterized by altered but active biosynthetic processes and continued replication of the chromosome. On removal of IFN- gamma , chlamydiae rapidly reentered the normal developmental cycle and reversed transcriptional changes associated with cytokine treatment. The coordinated transcriptional response to IFN- gamma implies that a chlamydial response stimulon has evolved to control the transition between acute and persistent growth of the pathogen. In contrast to the paradigm of persistence as a general stress response, our findings suggest that persistence is an alternative life cycle used by chlamydiae to avoid the host immune response. JF - Proceedings of the National Academy of Sciences, USA AU - Belland, R J AU - Nelson, DE AU - Virok, D AU - Crane, D D AU - Hogan, D AU - Sturdevant, D AU - Beatty, W L AU - Caldwell, H D AD - Laboratories of Intracellular Parasites and Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, hcaldwell@niaid.nih.gov Y1 - 2003/12/23/ PY - 2003 DA - 2003 Dec 23 SP - 15971 EP - 15976 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 26 SN - 0027-8424, 0027-8424 KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Proteolysis KW - g-Interferon KW - Replication KW - Transcription KW - Growth KW - Cell division KW - ^g-Interferon KW - Immune response KW - Chlamydia KW - J 02726:RNA and ribosomes KW - N 14552:Effects of hormones UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19260197?accountid=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=Transcriptome+analysis+of+chlamydial+growth+during+IFN-+gamma+-mediated+persistence+and+reactivation&rft.au=Belland%2C+R+J%3BNelson%2C+DE%3BVirok%2C+D%3BCrane%2C+D+D%3BHogan%2C+D%3BSturdevant%2C+D%3BBeatty%2C+W+L%3BCaldwell%2C+H+D&rft.aulast=Belland&rft.aufirst=R&rft.date=2003-12-23&rft.volume=100&rft.issue=26&rft.spage=15971&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.2535394100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia; Transcription; Immune response; Cell division; Replication; Proteolysis; Growth; g-Interferon; ^g-Interferon DO - http://dx.doi.org/10.1073/pnas.2535394100 ER - TY - JOUR T1 - Induction of colitis by a CD4 super(+) T cell clone specific for a bacterial epitope AN - 19254548; 5831626 AB - It is now well established that the intestinal flora plays an important role in the pathogenesis of inflammatory bowel disease (IBD). However, whether bacteria serve as the sole target of the immune response in this process or whether they act indirectly by triggering an anti-self response is still unclear. We have previously shown that specific pathogen-free IL-10-deficient (IL-10 KO) mice develop a T helper (Th1)-cytokine associated colitis after experimental infection with Helicobacter hepaticus. We here show that H. hepaticus Ag (SHelAg)-specific CD4 super(+) Th1 clones transfer disease to H. hepaticus-infected T cell-deficient RAG KO hosts. Importantly, uninfected recipients of the SHelAg-specific clones did not develop intestinal inflammation, and a control Schistosoma mansoni-specific Th1 clone did not induce colitis upon transfer to infected RAG KO mice. The disease-inducing T cell clones recognized antigen(s) (Ag) specifically expressed by certain Helicobacter species as they responded when stimulated in vitro with H. hepaticus and Helicobacter typhlonius Ag, but not when cultured with Ag preparations from Helicobacter pylori, various non-helicobacter bacteria, or with cecal bacterial lysate from uninfected mice. Characterization of the Ag specificity of one of the clones showed that it reacts uniquely with a 15-mer peptide epitope on the flagellar hook protein (FlgE) of H. hepaticus presented by I-A. Together, our results demonstrate that colitis can be induced by clonal T cell populations that are highly specific for target Ag on intestinal bacteria, suggesting that an aberrant T cell response directed against gut flora is sufficient to trigger IBD. JF - Proceedings of the National Academy of Sciences, USA AU - Kullberg, M C AU - Andersen, J F AU - Gorelick, P L AU - Caspar, P AU - Suerbaum, S AU - Fox, J G AU - Cheever, A W AU - Jankovic, D AU - Sher, A AD - Immunobiology Section and Laboratory of Malaria and Vector Research, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, mkullberg@niaid.nih.gov Y1 - 2003/12/23/ PY - 2003 DA - 2003 Dec 23 SP - 15830 EP - 15835 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 26 SN - 0027-8424, 0027-8424 KW - mice KW - CD4 antigen KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Helper cells KW - Helicobacter typhlonius KW - Inflammatory bowel diseases KW - Helicobacter hepaticus KW - Lymphocytes T KW - Colitis KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms KW - F 06756:Function UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19254548?accountid=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=Induction+of+colitis+by+a+CD4+super%28%2B%29+T+cell+clone+specific+for+a+bacterial+epitope&rft.au=Kullberg%2C+M+C%3BAndersen%2C+J+F%3BGorelick%2C+P+L%3BCaspar%2C+P%3BSuerbaum%2C+S%3BFox%2C+J+G%3BCheever%2C+A+W%3BJankovic%2C+D%3BSher%2C+A&rft.aulast=Kullberg&rft.aufirst=M&rft.date=2003-12-23&rft.volume=100&rft.issue=26&rft.spage=15830&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.2534546100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - The sequence reported in this paper has been deposited in the GenBank database (accession no. AJ583505). N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Helicobacter hepaticus; Helicobacter typhlonius; Colitis; Lymphocytes T; Helper cells; Inflammatory bowel diseases; CD4 antigen DO - http://dx.doi.org/10.1073/pnas.2534546100 ER - TY - JOUR T1 - Hypermethylation of the Ink4b locus in murine myeloid leukemia and increased susceptibility to leukemia in p15(Ink4b)-deficient mice. AN - 71509526; 14681685 AB - The Ink4b gene (Cdkn2b) encodes p15(Ink4b), a cyclin-dependent kinase inhibitor. It has been implicated in playing a role in the development of acute myeloid leukemia (AML) in man, since it is hypermethylated with high frequency. We provide evidence that the gene is a tumor suppressor for myeloid leukemia in mice. The evidence is twofold: (1) retrovirus-induced myeloid leukemias of the myelomonocytic phenotype were found to have hypermethylation of the 5' CpG island of the Ink4b gene, and this could be correlated with reduced mRNA expression, as demonstrated by TaqMan real-time PCR. p15(Ink4b) mRNA expression in a leukemia cell line, with hypermethylation at the locus, was induced following treatment with 5-aza-2'-deoxycytidine. (2) Targeted deletion of one allele in mice by removal of exon 2 increases their susceptibility to retrovirus-induced myeloid leukemia. Mice deficient in both alleles were not more susceptible to myeloid disease than those deficient in one allele, raising the possibility that there are opposing forces related to the development of myeloid leukemia in Ink4b null mice. JF - Oncogene AU - Wolff, Linda AU - Garin, Matthew T AU - Koller, Richard AU - Bies, Juraj AU - Liao, Wei AU - Malumbres, Marcos AU - Tessarollo, Lino AU - Powell, Douglas AU - Perella, Christine AD - Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. lwolff@helix.nih.gov Y1 - 2003/12/18/ PY - 2003 DA - 2003 Dec 18 SP - 9265 EP - 9274 VL - 22 IS - 58 SN - 0950-9232, 0950-9232 KW - Antimetabolites, Antineoplastic KW - 0 KW - Cdkn2b protein, mouse KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p15 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - RNA, Messenger KW - Tumor Suppressor Proteins KW - decitabine KW - 776B62CQ27 KW - Azacitidine KW - M801H13NRU KW - Index Medicus KW - Animals KW - Exons KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Transgenic KW - Antimetabolites, Antineoplastic -- pharmacology KW - Gene Deletion KW - Phenotype KW - Genotype KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Blotting, Southern KW - CpG Islands KW - Introns KW - Retroviridae -- genetics KW - Time Factors KW - Azacitidine -- pharmacology KW - DNA Methylation KW - Cell Cycle Proteins -- genetics KW - Leukemia, Myeloid, Acute -- genetics KW - Azacitidine -- analogs & derivatives KW - Cyclin-Dependent Kinase Inhibitor p16 -- metabolism KW - Cyclin-Dependent Kinase Inhibitor p16 -- genetics KW - Cell Cycle Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71509526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hypermethylation+of+the+Ink4b+locus+in+murine+myeloid+leukemia+and+increased+susceptibility+to+leukemia+in+p15%28Ink4b%29-deficient+mice.&rft.au=Wolff%2C+Linda%3BGarin%2C+Matthew+T%3BKoller%2C+Richard%3BBies%2C+Juraj%3BLiao%2C+Wei%3BMalumbres%2C+Marcos%3BTessarollo%2C+Lino%3BPowell%2C+Douglas%3BPerella%2C+Christine&rft.aulast=Wolff&rft.aufirst=Linda&rft.date=2003-12-18&rft.volume=22&rft.issue=58&rft.spage=9265&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-21 N1 - Date created - 2003-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. AN - 71484879; 14695133 AB - Liver metastases are the sole or life-limiting component of disease in the majority of patients with ocular melanoma who recur. Because median survival after diagnosis of liver metastases is short and no satisfactory treatment options exist, we have conducted clinical trials evaluating isolated hepatic perfusion (IHP) for patients afflicted with this condition. Twenty-nine patients (male: 14, female: 15; mean age, 49 years) with unresectable liver metastases from ocular melanoma were treated with a 60-min hyperthermic IHP using 1.5 mg/kg of melphalan (mean total dose 105 mg). Via laparotomy, perfusion inflow was established with a cannula in the gastroduodenal artery and outflow via a cannula positioned in an isolated segment of the retrohepatic inferior vena cava. Portal and infra-renal inferior vena cava blood flow was shunted externally to the axillary vein using a veno-veno bypass circuit. Patients were assessed for toxicity, radiographic response, and survival. There was no treatment related mortality and transient grade 3/4 hepatic toxicity was observed in 19 patients (65%). Mean length of operation and hospital stay was 8.3 h and 10 days, respectively. There were 3 (10%) complete responses (duration: 12, 14+, 15 months) and 15 partial responses (52%; mean duration: 10 months). The initial site of disease progression included liver in 17 of 25 patients (68%) who recurred. At a median follow-up of 30.7 months the median actuarial progression-free and overall survivals were 8 and 12.1 months, respectively. IHP with melphalan alone results in significant regression of established liver metastases for patients with ocular melanoma. However, after IHP, disease progression is most commonly observed in the liver, and survival after disease progression is short. On the basis of a pattern of tumor progression predominantly in liver, continued clinical evaluation of hepatic directed therapy in this patient population is justified. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Alexander, H Richard AU - Libutti, Steven K AU - Pingpank, James F AU - Steinberg, Seth M AU - Bartlett, David L AU - Helsabeck, Cynthia AU - Beresneva, Tatiana AD - Surgical Metabolism Section, Surgery Branch, Center for Cancer, National Cancer Institute,NIH, Bethesda, Maryland 20892-1502, USA. Richard_Alexander@nih.gov Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 6343 EP - 6349 VL - 9 IS - 17 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Magnetic Resonance Imaging KW - Disease-Free Survival KW - Humans KW - Adult KW - Treatment Outcome KW - Disease Progression KW - Aged KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Liver -- pathology KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Perfusion KW - Melanoma -- pathology KW - Hyperthermia, Induced KW - Melphalan -- therapeutic use KW - Eye Neoplasms -- pathology KW - Liver Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71484879?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hyperthermic+isolated+hepatic+perfusion+using+melphalan+for+patients+with+ocular+melanoma+metastatic+to+liver.&rft.au=Alexander%2C+H+Richard%3BLibutti%2C+Steven+K%3BPingpank%2C+James+F%3BSteinberg%2C+Seth+M%3BBartlett%2C+David+L%3BHelsabeck%2C+Cynthia%3BBeresneva%2C+Tatiana&rft.aulast=Alexander&rft.aufirst=H&rft.date=2003-12-15&rft.volume=9&rft.issue=17&rft.spage=6343&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 - 2004-08-05 N1 - Date created - 2003-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity. AN - 71484415; 14695217 AB - Ansamycin antibiotics inhibit function of the heat shock protein (HSP) 90, causing selective degradation of several intracellular proteins regulating such processes as proliferation, cell cycle regulation, and prosurvival signaling cascades. HSP90 has been identified previously as a molecular target for anticancer agents, including ionizing radiation (IR). Therefore, we hypothesized that the ansamycin geldanamycin and its 17-allylamino-17-demethoxy analog (17-AAG), which inhibit HSP90, would enhance tumor cell susceptibility to the cytotoxicity of IR. Treatment of two human cervical carcinoma cell lines (HeLa and SiHa) with geldanamycin and 17-AAG resulted in cytotoxicity and, when combined with IR, enhanced the radiation response, each effect with a temporal range from 6 to 48 h after drug exposure. In addition, mouse in vivo models using 17-AAG at clinically achievable concentrations yielded results that paralleled the in vitro radiosensitization studies of both single and fractioned courses of irradiation. The increase in IR-induced cell death appears to be attributable to a combination of both programmed and nonprogrammed cell death. We also measured total levels of several prosurvival and apoptotic signaling proteins. Akt1, extracellular signal-regulated kinase-1, Glut-1, HER-2/neu, Lyn, cAMP-dependent protein kinase, Raf-1, and vascular endothelial growth factor expression were down-regulated in 17-AAG-treated cells, identifying these factors as molecular markers and potential therapeutic targets. Finally, a series of immortalized and human papillomavirus-transformed cell lines were used to demonstrate that the radiosensitizing effects of 17-AAG were limited to transformed cells, suggesting a possible differential cytotoxic effect. This work shows that altered HSP90 function induces significant tumor cytotoxicity and radiosensitization, suggesting a potential therapeutic utility. JF - Cancer research AU - Bisht, Kheem S AU - Bradbury, C Matthew AU - Mattson, David AU - Kaushal, Aradhana AU - Sowers, Anastasia AU - Markovina, Stephanie AU - Ortiz, Karen L AU - Sieck, Leah K AU - Isaacs, Jennifer S AU - Brechbiel, Martin W AU - Mitchell, James B AU - Neckers, Leonard M AU - Gius, David AD - Radiation Oncology Branch and. Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1002, USA. Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 8984 EP - 8995 VL - 63 IS - 24 SN - 0008-5472, 0008-5472 KW - Antibiotics, Antineoplastic KW - 0 KW - Benzoquinones KW - HSP90 Heat-Shock Proteins KW - Lactams, Macrocyclic KW - Quinones KW - Radiation-Sensitizing Agents KW - Rifabutin KW - 1W306TDA6S KW - tanespimycin KW - 4GY0AVT3L4 KW - geldanamycin KW - Z3K3VJ16KU KW - Index Medicus KW - Animals KW - Combined Modality Therapy KW - Dose-Response Relationship, Drug KW - HeLa Cells KW - Humans KW - Mice KW - Mice, Nude KW - Signal Transduction -- drug effects KW - Mice, Inbred C3H KW - Xenograft Model Antitumor Assays KW - Drug Synergism KW - Female KW - Rifabutin -- analogs & derivatives KW - Uterine Cervical Neoplasms -- drug therapy KW - Antibiotics, Antineoplastic -- pharmacology KW - Radiation-Sensitizing Agents -- pharmacology KW - HSP90 Heat-Shock Proteins -- physiology KW - Quinones -- pharmacology KW - Uterine Cervical Neoplasms -- radiotherapy KW - Rifabutin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71484415?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Geldanamycin+and+17-allylamino-17-demethoxygeldanamycin+potentiate+the+in+vitro+and+in+vivo+radiation+response+of+cervical+tumor+cells+via+the+heat+shock+protein+90-mediated+intracellular+signaling+and+cytotoxicity.&rft.au=Bisht%2C+Kheem+S%3BBradbury%2C+C+Matthew%3BMattson%2C+David%3BKaushal%2C+Aradhana%3BSowers%2C+Anastasia%3BMarkovina%2C+Stephanie%3BOrtiz%2C+Karen+L%3BSieck%2C+Leah+K%3BIsaacs%2C+Jennifer+S%3BBrechbiel%2C+Martin+W%3BMitchell%2C+James+B%3BNeckers%2C+Leonard+M%3BGius%2C+David&rft.aulast=Bisht&rft.aufirst=Kheem&rft.date=2003-12-15&rft.volume=63&rft.issue=24&rft.spage=8984&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 - 2004-03-11 N1 - Date created - 2003-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo antitumor activity of interleukin 21 mediated by natural killer cells. AN - 71484268; 14695220 AB - Immunotherapy with high-dose interleukin (IL) 2 has been shown to successfully treat tumors in animal models and cause dramatic tumor regressions in some patients with metastatic melanoma, renal cell carcinoma, and non-Hodgkin's lymphoma. However, toxicity associated with IL-2 administration has compromised its widespread use in the clinic. IL-21 is a more recently discovered cytokine produced by activated CD4(+) T cells that shares significant sequence homology to IL-2, IL-4, and IL-15. Because IL-21 and IL-2 and their receptors share significant sequence similarities and both cytokines can stimulate T and natural killer (NK) cells, we sought to study whether IL-21, like IL-2, exhibits antitumor effects in vivo. In this study, we treated established s.c. tumor in mice by systemically administering plasmid DNA encoding murine IL-21 using a hydrodynamics-based gene delivery technique. Administration of IL-21 plasmid DNA resulted in high levels of circulating IL-21 in vivo. Treatment of tumor-bearing mice with IL-21 plasmid DNA significantly inhibited the growth of B16 melanoma and MCA205 fibrosarcoma in a dose-dependent manner without significant toxicity and increased the survival rate, compared with mice treated with control plasmid DNA. In vivo depletion of either CD4(+) or CD8(+) T cells did not affect IL-21-mediated antitumor activity. However, depletion of NK cells completely abolished IL-21-induced tumor inhibition. Consistent with this, the antitumor activity of IL-21 seemed to be mediated through enhanced cytolytic activity of NK cells. Our study suggests that IL-21 has significant antitumor activity and may have therapeutic potentials as an antitumor agent in the clinic. JF - Cancer research AU - Wang, Gang AU - Tschoi, Mary AU - Spolski, Rosanne AU - Lou, Yanyan AU - Ozaki, Katsutoshi AU - Feng, Chiguang AU - Kim, Grace AU - Leonard, Warren J AU - Hwu, Patrick AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. gangwang@mdanderson.org Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 9016 EP - 9022 VL - 63 IS - 24 SN - 0008-5472, 0008-5472 KW - Cytokines KW - 0 KW - Interleukin-2 KW - Interleukins KW - interleukin-21 KW - Index Medicus KW - Animals KW - Gene Transfer Techniques KW - Plasmids -- genetics KW - Cytokines -- secretion KW - Mice KW - CD4-CD8 Ratio KW - Melanoma, Experimental -- therapy KW - Melanoma, Experimental -- immunology KW - Interleukin-2 -- blood KW - Fibrosarcoma -- therapy KW - Cell Division -- immunology KW - Fibrosarcoma -- immunology KW - T-Lymphocyte Subsets -- immunology KW - Mice, Inbred C57BL KW - Interleukin-2 -- secretion KW - Melanoma, Experimental -- genetics KW - Fibrosarcoma -- genetics KW - Interleukins -- biosynthesis KW - Interleukins -- immunology KW - Killer Cells, Natural -- immunology KW - Interleukins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71484268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vivo+antitumor+activity+of+interleukin+21+mediated+by+natural+killer+cells.&rft.au=Wang%2C+Gang%3BTschoi%2C+Mary%3BSpolski%2C+Rosanne%3BLou%2C+Yanyan%3BOzaki%2C+Katsutoshi%3BFeng%2C+Chiguang%3BKim%2C+Grace%3BLeonard%2C+Warren+J%3BHwu%2C+Patrick&rft.aulast=Wang&rft.aufirst=Gang&rft.date=2003-12-15&rft.volume=63&rft.issue=24&rft.spage=9016&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 - 2004-03-11 N1 - Date created - 2003-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phorbol ester stimulates the nonhypoxic induction of a novel hypoxia-inducible factor 1alpha isoform: implications for tumor promotion. AN - 71479530; 14695184 AB - Hypoxia-inducible factor-1 (HIF-1), which is present at higher levels in human tumors, plays important roles in tumor promotion. It is composed of HIF-1alpha and HIF-1beta subunits and its activity depends on the amount of HIF-1alpha, which is tightly controlled by cellular oxygen tension. In addition to hypoxia, various nonhypoxic stimuli can stabilize HIF-1alpha in tumor cells, implying that both hypoxic and nonhypoxic stimuli contribute to the overexpression of HIF-1alpha in tumors. On the other hand, phorbol esters such as phorbol-12-myristate-13-acetate (PMA) are known to be potent tumor promoters. Here, we identified a novel HIF-1alpha isoform, which is regulated primarily by PMA. The variant mRNA lacks exon 11 and produces a 785-amino acid isoform (HIF-1alpha(785)) without altering the reading frame and therefore the COOH-terminal transcriptional activity. HIF-1alpha(785) is induced markedly by PMA and heat shock, the latter of which is also known to induce HIF-1alpha. HIF-1alpha(785) escapes from lysine acetylation because of the loss of Lys(532) and was stabilized under normoxic conditions. Its expression was blocked by reducing agents and by a mitogen-activated protein/extracellular signal-regulated kinase-1 inhibitor and enhanced by hydrogen peroxide. In addition, HIF-1alpha(785) overexpression strikingly enhanced tumor growth in vivo. These results suggest that HIF-1alpha(785) is induced by PMA under normoxic conditions via a redox-dependent mitogen-activated protein/extracellular signal-regulated kinase-1 pathway and that it plays an important role in tumor promotion. JF - Cancer research AU - Chun, Yang-Sook AU - Lee, Kyoung-Hwa AU - Choi, Eunjoo AU - Bae, Soo-Young AU - Yeo, Eun-Jin AU - Huang, L Eric AU - Kim, Myung-Suk AU - Park, Jong-Wan AD - Human Genome Research Institute and Cancer Research Institute, National Cancer Institute, NIH, Bethesda, Maryland, USA. Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 8700 EP - 8707 VL - 63 IS - 24 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Protein Isoforms KW - RNA, Messenger KW - Transcription Factors KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Humans KW - Cell Division -- physiology KW - Cell Hypoxia -- physiology KW - Cell Line, Tumor KW - Mice KW - Mice, Nude KW - RNA, Messenger -- genetics KW - Transcriptional Activation KW - DNA Methylation KW - Transfection KW - Alternative Splicing KW - Up-Regulation -- drug effects KW - Signal Transduction -- drug effects KW - Transcription Factors -- physiology KW - Carcinogens -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71479530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phorbol+ester+stimulates+the+nonhypoxic+induction+of+a+novel+hypoxia-inducible+factor+1alpha+isoform%3A+implications+for+tumor+promotion.&rft.au=Chun%2C+Yang-Sook%3BLee%2C+Kyoung-Hwa%3BChoi%2C+Eunjoo%3BBae%2C+Soo-Young%3BYeo%2C+Eun-Jin%3BHuang%2C+L+Eric%3BKim%2C+Myung-Suk%3BPark%2C+Jong-Wan&rft.aulast=Chun&rft.aufirst=Yang-Sook&rft.date=2003-12-15&rft.volume=63&rft.issue=24&rft.spage=8700&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 - 2004-03-11 N1 - Date created - 2003-12-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Shedding of the type II IL-1 decoy receptor requires a multifunctional aminopeptidase, aminopeptidase regulator of TNF receptor type 1 shedding. AN - 71443416; 14662887 AB - Proteolytic cleavage of the extracellular domain of the type II IL-1 decoy receptor (IL-1RII) generates soluble IL-1-binding proteins that prevent excessive bioactivity by binding free IL-1. In this study we report that an aminopeptidase, aminopeptidase regulator of TNFR1 shedding (ARTS-1), is required for IL-1RII shedding. Coimmunoprecipitation experiments demonstrate an association between endogenous membrane-associated ARTS-1 and a 47-kDa IL-1RII, consistent with ectodomain cleavage of the membrane-bound receptor. A direct correlation exists between ARTS-1 protein expression and IL-1RII shedding, as cell lines overexpressing ARTS-1 have increased IL-1RII shedding and decreased membrane-associated IL-1RII. Basal IL-1RII shedding is absent from ARTS-1 knockout cell lines, demonstrating that ARTS-1 is required for constitutive IL-1RII shedding. Similarly, PMA-mediated IL-1RII shedding is almost entirely ARTS-1-dependent. ARTS-1 expression also enhances ionomycin-induced IL-1RII shedding. ARTS-1 did not alter levels of membrane-associated IL-1RI or IL-1R antagonist release from ARTS-1 cell lines, which suggests that the ability of ARTS-1 to promote shedding of IL-1R family members may be specific for IL-1RII. Further, increased IL-1RII shedding by ARTS-1-overexpressing cells attenuates the biological activity of IL-1beta. We conclude that the ability of ARTS-1 to enhance IL-1RII shedding represents a new mechanism by which IL-1-induced cellular events can be modulated. As ARTS-1 also promotes the shedding of the structurally unrelated 55-kDa, type I TNF receptor and the IL-6R, we propose that ARTS-1 may play an important role in regulating innate immune and inflammatory responses by increasing cytokine receptor shedding. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Cui, Xinle AU - Rouhani, Farshid N AU - Hawari, Feras AU - Levine, Stewart J AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1590, USA. Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 6814 EP - 6819 VL - 171 IS - 12 SN - 0022-1767, 0022-1767 KW - Antigens, CD KW - 0 KW - Carrier Proteins KW - GPI-Linked Proteins KW - Interleukin-1 KW - Interleukin-8 KW - Lipoproteins KW - Membrane Proteins KW - Minor Histocompatibility Antigens KW - Multienzyme Complexes KW - Protein Isoforms KW - Receptors, Interleukin-1 KW - Receptors, Tumor Necrosis Factor KW - Receptors, Tumor Necrosis Factor, Member 10c KW - Receptors, Tumor Necrosis Factor, Type I KW - TNFRSF10C protein, human KW - Tumor Necrosis Factor Decoy Receptors KW - Metalloproteases KW - EC 3.4.- KW - Aminopeptidases KW - EC 3.4.11.- KW - ERAP1 protein, human KW - Metalloendopeptidases KW - EC 3.4.24.- KW - ZMPSTE24 protein, human KW - EC 3.4.24.84 KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Interleukin-1 -- pharmacology KW - Lipoproteins -- deficiency KW - Cell Membrane -- enzymology KW - Humans KW - Cell Membrane -- genetics KW - Membrane Proteins -- genetics KW - Membrane Proteins -- deficiency KW - Calcium -- metabolism KW - Cell Membrane -- immunology KW - Interleukin-8 -- secretion KW - Protein Isoforms -- metabolism KW - Cell Line, Tumor KW - Precipitin Tests KW - Lipoproteins -- genetics KW - Metalloproteases -- deficiency KW - Catalytic Domain -- genetics KW - Calcium -- physiology KW - Catalytic Domain -- physiology KW - Metalloproteases -- genetics KW - Mutagenesis, Insertional KW - Multienzyme Complexes -- metabolism KW - Aminopeptidases -- physiology KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- genetics KW - Multienzyme Complexes -- genetics KW - Aminopeptidases -- genetics KW - Aminopeptidases -- metabolism KW - Antigens, CD -- metabolism KW - Carrier Proteins -- physiology KW - Receptors, Tumor Necrosis Factor -- metabolism KW - Multienzyme Complexes -- physiology KW - Receptors, Interleukin-1 -- metabolism KW - Receptors, Interleukin-1 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71443416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Shedding+of+the+type+II+IL-1+decoy+receptor+requires+a+multifunctional+aminopeptidase%2C+aminopeptidase+regulator+of+TNF+receptor+type+1+shedding.&rft.au=Cui%2C+Xinle%3BRouhani%2C+Farshid+N%3BHawari%2C+Feras%3BLevine%2C+Stewart+J&rft.aulast=Cui&rft.aufirst=Xinle&rft.date=2003-12-15&rft.volume=171&rft.issue=12&rft.spage=6814&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 - 2004-03-15 N1 - Date created - 2003-12-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Immunol. 2004 Aug 1;173(3):following 2198 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential requirement for A2a and A3 adenosine receptors for the protective effect of inosine in vivo. AN - 71438945; 12947007 AB - Inosine is an endogenous nucleoside with immunosuppressive properties that is known to inhibit the accumulation of proinflammatory cytokines and protect mice from endotoxin-induced inflammation and lung tissue damage. There are no known receptors specific for inosine, but A3 adenosine receptors (A3Rs) have been shown to bind inosine, resulting in mast cell degranulation and increased vascular permeability. The present study specifically addresses the requirement for A2aR and/or A3R for the protective effect of inosine in 2 experimental in vivo models of inflammatory disease. The data show that A3R is essential for protection against ConA-induced fulminant hepatitis since only A3R-expressing mice were protected by inosine whereas wild-type and A2aR-deficient mice exhibited severe liver damage even after administration of inosine. In addition, we show in a model of LPS-induced endotoxemia that inosine protected both A2aR-/- and A3R-/- mice from inflammation, but not A2aA3R double-null mice, indicating that in this model both A2aR and A3R were used by inosine. Thus, we demonstrate that A2a and A3 adenosine receptors are differentially utilized by inosine for the down-regulation of tissue damage under different inflammatory conditions in vivo. JF - Blood AU - Gomez, Gregorio AU - Sitkovsky, Michail V AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10/11N311, 10 Center Dr-MSC 1892, Bethesda, MD 20892-1892, USA. Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 4472 EP - 4478 VL - 102 IS - 13 SN - 0006-4971, 0006-4971 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Immunosuppressive Agents KW - Receptor, Adenosine A2A KW - Receptor, Adenosine A3 KW - Tumor Necrosis Factor-alpha KW - Concanavalin A KW - 11028-71-0 KW - Inosine KW - 5A614L51CT KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Hepatocytes -- drug effects KW - Alanine Transaminase -- blood KW - Concanavalin A -- toxicity KW - Apoptosis -- drug effects KW - Tumor Necrosis Factor-alpha -- analysis KW - Mice, Inbred C57BL KW - Disease Models, Animal KW - Mice KW - Male KW - Mice, Knockout KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Chemical and Drug Induced Liver Injury -- pathology KW - Inosine -- therapeutic use KW - Receptor, Adenosine A2A -- genetics KW - Receptor, Adenosine A2A -- deficiency KW - Chemical and Drug Induced Liver Injury -- drug therapy KW - Chemical and Drug Induced Liver Injury -- immunology KW - Immunosuppressive Agents -- pharmacology KW - Receptor, Adenosine A2A -- physiology KW - Endotoxemia -- immunology KW - Inosine -- pharmacology KW - Receptor, Adenosine A3 -- deficiency KW - Receptor, Adenosine A2A -- drug effects KW - Receptor, Adenosine A3 -- physiology KW - Receptor, Adenosine A3 -- genetics KW - Receptor, Adenosine A3 -- drug effects KW - Immunosuppressive Agents -- therapeutic use KW - Endotoxemia -- drug therapy KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71438945?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differential+requirement+for+A2a+and+A3+adenosine+receptors+for+the+protective+effect+of+inosine+in+vivo.&rft.au=Gomez%2C+Gregorio%3BSitkovsky%2C+Michail+V&rft.aulast=Gomez&rft.aufirst=Gregorio&rft.date=2003-12-15&rft.volume=102&rft.issue=13&rft.spage=4472&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-21 N1 - Date created - 2003-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic alterations in the Catnb gene but not the H-ras gene in hepatocellular neoplasms and hepatoblastomas of B6C3F(1) mice following exposure to diethanolamine for 2 years. AN - 71426995; 14642737 AB - The present study characterized the immunohistochemical localization of beta-catenin protein in hepatocellular neoplasms and hepatoblastomas in B6C3F(1) mice exposed to diethanolamine (DEA) for 2 years and evaluated genetic alterations in the Catnb and H-ras genes which are known to play important roles in the pathogenesis of liver malignancies. Genomic DNA was isolated from paraffin sections of each liver tumor. Catnb exon 2 (corresponds to exon 3 in human) genetic alterations were identified in 18/18 (100%) hepatoblastomas from DEA exposed mice. Deletion mutations (15/18, 83%) were identified more frequently than point mutations (6/18, 33%) in hepatoblastomas. Eleven of 34 (32%) hepatocellular adenomas and carcinomas from DEA treated mice had mutations in exon 2 of the beta-catenin gene, while only 1 of 10 spontaneous neoplasms had a deletion mutation of codon 5-6. Common to all liver neoplasms (hepatocellular adenomas, carcinomas and hepatoblastomas) was membrane staining for the beta-catenin protein, while cytoplasmic and nuclear staining was observed only in hepatoblastomas. The lack of H-ras mutations in hepatocellular neoplasms and hepatoblastomas suggests that the ras signal transduction pathway is not involved in the development of liver tumors following DEA exposure which is different from that of spontaneous liver tumors that often contain H-ras mutations. JF - Chemico-biological interactions AU - Hayashi, Shim-mo AU - Ton, Thai Vu AU - Hong, Hue-Hua L AU - Irwin, Richard D AU - Haseman, Joseph K AU - Devereux, Theodora R AU - Sills, Robert C AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 251 EP - 261 VL - 146 IS - 3 SN - 0009-2797, 0009-2797 KW - CTNNB1 protein, mouse KW - 0 KW - Carcinogens KW - Cytoskeletal Proteins KW - DNA, Neoplasm KW - Ethanolamines KW - Trans-Activators KW - beta Catenin KW - diethanolamine KW - AZE05TDV2V KW - Index Medicus KW - Adenoma, Liver Cell -- metabolism KW - Animals KW - Genes, ras -- drug effects KW - Mice KW - Adenoma, Liver Cell -- chemically induced KW - Polymorphism, Single-Stranded Conformational KW - DNA, Neoplasm -- drug effects KW - Adenoma, Liver Cell -- genetics KW - DNA, Neoplasm -- genetics KW - Time Factors KW - Immunohistochemistry KW - Mutation KW - Female KW - Male KW - Trans-Activators -- metabolism KW - Liver Neoplasms, Experimental -- genetics KW - Trans-Activators -- genetics KW - Liver Neoplasms, Experimental -- metabolism KW - Carcinogens -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Ethanolamines -- toxicity KW - Cytoskeletal Proteins -- metabolism KW - Cytoskeletal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71426995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemico-biological+interactions&rft.atitle=Genetic+alterations+in+the+Catnb+gene+but+not+the+H-ras+gene+in+hepatocellular+neoplasms+and+hepatoblastomas+of+B6C3F%281%29+mice+following+exposure+to+diethanolamine+for+2+years.&rft.au=Hayashi%2C+Shim-mo%3BTon%2C+Thai+Vu%3BHong%2C+Hue-Hua+L%3BIrwin%2C+Richard+D%3BHaseman%2C+Joseph+K%3BDevereux%2C+Theodora+R%3BSills%2C+Robert+C&rft.aulast=Hayashi&rft.aufirst=Shim-mo&rft.date=2003-12-15&rft.volume=146&rft.issue=3&rft.spage=251&rft.isbn=&rft.btitle=&rft.title=Chemico-biological+interactions&rft.issn=00092797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-04 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Health services research: drug use and human immunodeficiency virus in the United States. AN - 71420518; 14648461 AB - Major research findings show gaps in health services research on the prevalence and outcomes of patient- and organization-level human immunodeficiency virus (HIV) and drug abuse prevention and treatment services. The latest thrust of health services research on translational research issues includes informing and training practitioners about new, proven drug abuse treatment interventions; changing treatment organizations (creating a climate for change and building a culture to sustain change); and financing new treatments. Findings defining the direct relationship between the quality of drug abuse treatment and the patients' program completion, the perception of the staff by the patient, feelings of self-empowerment and mitigation of patient and organizational readiness, the superiority of integrated care, and the primary reasons for delays in HIV-infected substance-using patients seeking care are included. More needs to be done to increase the participation of substance abuse programs in teaching about and implementing HIV prevention and developing means to modulate or eliminate barriers to the integration of HIV and substance abuse care. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Flanzer, Jerry AD - Services Research Branch, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland 20892, USA. jf199i@nih.gov Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - S439 EP - S444 VL - 37 Suppl 5 KW - Index Medicus KW - United States KW - Substance Abuse Treatment Centers KW - Humans KW - Delivery of Health Care KW - HIV KW - Substance-Related Disorders -- therapy KW - HIV Infections -- therapy KW - Health Services Research KW - Delivery of Health Care, Integrated -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71420518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Health+services+research%3A+drug+use+and+human+immunodeficiency+virus+in+the+United+States.&rft.au=Flanzer%2C+Jerry&rft.aulast=Flanzer&rft.aufirst=Jerry&rft.date=2003-12-15&rft.volume=37+Suppl+5&rft.issue=&rft.spage=S439&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-13 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bloodborne and sexually transmitted infections in drug abusers in the United States, Latin America, the Caribbean, and Spain. AN - 71419275; 14648442 AB - In the United States, approximately 1 million Americans are infected with human immunodeficiency virus (HIV), and several thousand new infections are reported each year. More than one-third of cases of acquired immunodeficiency syndrome (AIDS) are associated with injection drug use. An estimated 1.8 million adults and children are currently living with HIV in Latin America and the Caribbean, and injection drug abuse remains a major factor in initial exposures to HIV in these parts of the world. Although only 3 cases of AIDS related to drug abuse have been reported in Bolivia, a country with a nascent epidemic, >19,000 cases of AIDS have been reported in Argentina and >22,000 in Brazil, with a significant number associated with injection drug use. Extensive epidemiological and clinical research has been conducted in the United States and elsewhere to determine the extent and nature of the problem and to design and develop interventions (prevention and treatment) for drug abusers infected with HIV. The articles in this supplement present a current view of the nature and extent of the bloodborne and sexually transmitted infections in drug abusers and their partners in the Western Hemisphere. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Khalsa, Jag H AU - Francis, Henry AU - Mazin, Rafael AD - Center on AIDS and Other Medical Consequences of Drug Abuse, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, USA. jk98p@nih.gov Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - S331 EP - S337 VL - 37 Suppl 5 KW - Index Medicus KW - Caribbean Region -- epidemiology KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - Latin America -- epidemiology KW - Humans KW - Adult KW - Acquired Immunodeficiency Syndrome -- transmission KW - Child KW - Spain -- epidemiology KW - United States -- epidemiology KW - HIV Infections -- transmission KW - Substance-Related Disorders -- complications KW - HIV Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71419275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Bloodborne+and+sexually+transmitted+infections+in+drug+abusers+in+the+United+States%2C+Latin+America%2C+the+Caribbean%2C+and+Spain.&rft.au=Khalsa%2C+Jag+H%3BFrancis%2C+Henry%3BMazin%2C+Rafael&rft.aulast=Khalsa&rft.aufirst=Jag&rft.date=2003-12-15&rft.volume=37+Suppl+5&rft.issue=&rft.spage=S331&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-13 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carbon monoxide neurotoxicity: transient inhibition of avoidance response and delayed microglia reaction in the absence of neuronal death. AN - 71386107; 14636696 AB - Carbon monoxide exposure produces neurobehavioral effects associated with the level of carboxyhemoglobin (COHb) in the blood. A threshold has been proposed of approximately 35% COHb for the manifestation of disruption in neurobehavioral tasks. The effects of CO exposure producing 30-40% carboxyhemoglobin (COHb) levels in young adult male Fischer 344 rats were examined with regard to clinical signs of toxicity, performance on a previously learned avoidance procedure, and neuronal and glia histopathology. High levels of exposure (4000 ppm) for 15 min were imposed on either a background blood COHb level of 5% produced by a 2 h exposure to 50 ppm CO or a control background from conditioned-air exposure. Upon removal from the nose-only inhalation holder, signs of mild lethargy and decreased activity were evident for 2 min for conditioned-air controls and 50 ppm CO exposure groups and 3-4 min following 4000 ppm CO. Performance on a two-way shuttle box active avoidance task showed no differences between 50 ppm CO rats and conditioned-air controls while the 4000 ppm CO exposed groups showed a significant decrease in avoidance and escape responses. Histological examination showed no evidence of delayed neuronal death or astrocyte reactivity in the hippocampus or cerebellum; however, a distinct focal staining of reactive microglia in both regions was evident in animals exposed to 4000 ppm CO. While 50 ppm CO (5% COHb) alone produced no disruption in avoidance performance, microglia staining in the cerebellum was significantly increased over conditioned-air controls. This regional and focal response of microglia suggests the need for further study regarding such subtle cellular changes and their relationship with COHb levels. JF - Toxicology AU - Brunssen, Susan H AU - Morgan, Daniel L AU - Parham, Frederick M AU - Harry, G Jean AD - Laboratory of Molecular Toxicology, NIEHS, 111 TW Alexander Drive, PO Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 51 EP - 63 VL - 194 IS - 1-2 SN - 0300-483X, 0300-483X KW - Carbon Monoxide KW - 7U1EE4V452 KW - Carboxyhemoglobin KW - 9061-29-4 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Frontal Lobe -- drug effects KW - Cerebellum -- pathology KW - Hippocampus -- drug effects KW - Rats KW - Carboxyhemoglobin -- metabolism KW - Rats, Inbred F344 KW - Necrosis KW - Frontal Lobe -- pathology KW - Cerebellum -- drug effects KW - Hippocampus -- pathology KW - Administration, Inhalation KW - Time Factors KW - Male KW - Behavior, Animal -- drug effects KW - Neurons -- drug effects KW - Carbon Monoxide -- toxicity KW - Avoidance Learning -- drug effects KW - Microglia -- pathology KW - Microglia -- drug effects KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71386107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Industrial+health&rft.atitle=A+proportionate+cancer+morbidity+ratio+study+of+workers+exposed+to+chlorinated+organic+solvents+in+Taiwan.&rft.au=Chang%2C+Yung-Ming%3BTai%2C+Chi-Fu%3BLin%2C+Ruey+S%3BYang%2C+Sweo-Chung%3BChen%2C+Chiou-Jong%3BShih%2C+Tung-Sheng%3BLiou%2C+Saou-Hsing&rft.aulast=Chang&rft.aufirst=Yung-Ming&rft.date=2003-04-01&rft.volume=41&rft.issue=2&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Industrial+health&rft.issn=00198366&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-07 N1 - Date created - 2003-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - G-protein-coupled receptors at a glance. AN - 71382320; 14625380 JF - Journal of cell science AU - Kroeze, Wesley K AU - Sheffler, Douglas J AU - Roth, Bryan L AD - Departments of Biochemistry, Neurosciences and Psychiatry, NIMH Psychoactive Drug Screening Program, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA. Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 4867 EP - 4869 VL - 116 SN - 0021-9533, 0021-9533 KW - Ligands KW - 0 KW - Receptors, G-Protein-Coupled KW - Receptors, Serotonin, 5-HT2 KW - Rhodopsin KW - 9009-81-8 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Receptors, Serotonin, 5-HT2 -- genetics KW - Receptors, Serotonin, 5-HT2 -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Protein Structure, Tertiary KW - Protein Binding KW - Signal Transduction KW - Rhodopsin -- genetics KW - Receptors, G-Protein-Coupled -- drug effects KW - Receptors, G-Protein-Coupled -- metabolism KW - Receptors, G-Protein-Coupled -- genetics KW - Drug Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71382320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell+science&rft.atitle=G-protein-coupled+receptors+at+a+glance.&rft.au=Kroeze%2C+Wesley+K%3BSheffler%2C+Douglas+J%3BRoth%2C+Bryan+L&rft.aulast=Kroeze&rft.aufirst=Wesley&rft.date=2003-12-15&rft.volume=116&rft.issue=&rft.spage=4867&rft.isbn=&rft.btitle=&rft.title=Journal+of+cell+science&rft.issn=00219533&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-17 N1 - Date created - 2003-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct activation by dopamine of recombinant human 5-HT1A receptors: comparison with human 5-HT2C and 5-HT3 receptors. AN - 71254578; 14556235 AB - The effects of dopamine (DA) on the function of human 5-HT1A receptors expressed in Xenopus oocytes and CHO-K1 cells were investigated. In addition, the effect of DA on the activation of three different types of human 5-HT receptors (5-HT1A, 5-HT2C, and 5-HT3) were studied comparatively in Xenopus oocyte expression system. Application of 5-HT or DA in oocytes coexpressing 5-HT1A receptors and G-protein-activated inwardly rectifying potassium channels (GIRK1) induced inward currents with respective EC50 values of 4.2 nM and 11.2 microM. Maximal responses induced by DA were 85 +/- 4% of maximal 5-HT currents and DA responses were blocked by the specific 5-HT1A antagonist, WAY-100635 (50 nM). In CHO-K1 cells expressing 5-HT1A receptors, 5-HT and DA inhibited the specific binding of selective antagonist [3H]-8-OH-DPAT with IC50 values of 10.2 nM and 1.4 microM, and both 5-HT and DA inhibited the forskolin-induced accumulation of cAMP. In oocytes expressing 5-HT2C receptors, 5-HT and DA induced inward currents with respective EC50 values of 6.2 nM and 67.7 microM. Magnitudes of maximal DA induced currents were 42 +/- 3% of maximal 5-HT responses and blocked by the 5-HT2 antagonist, piperazine (1 microM). In oocytes expressing 5-HT3 receptors, 5-HT and DA induced fast inward currents with respective EC50 values of 2.1 microM and 266.3 microM. Maximal DA induced currents were 37 +/- 3% of maximal 5-HT responses and blocked the specific 5-HT3 antagonist LY-278584 (0.1 microM). Comparison of the potencies and efficacies of 5-HT and DA indicated that the relative potency of DA increased in the order of 5-HT3 > 5-HT1A > 5-HT2C, and relative efficacy increased in the order of 5-HT1A > 5-HT2C > 5-HT3. These results suggest that although DA activates different subtypes of human 5-HT receptors directly, the potency and efficacy of the binding site varies significantly among different receptors. JF - Synapse (New York, N.Y.) AU - Oz, Murat AU - Zhang, Li AU - Rotondo, Alessandro AU - Sun, Hui AU - Morales, Marisela AD - Cellular Neurobiology Branch, National Institute on Drug Abuse, National Institutes of Health, DHHS, Intramural Research Program, Baltimore, Maryland 21224, USA. moz@intra.nida.nih.gov Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 303 EP - 313 VL - 50 IS - 4 SN - 0887-4476, 0887-4476 KW - Chelating Agents KW - 0 KW - Dopamine Antagonists KW - G Protein-Coupled Inwardly-Rectifying Potassium Channels KW - Indazoles KW - Piperazines KW - Potassium Channels KW - Potassium Channels, Inwardly Rectifying KW - Pyridines KW - RNA, Messenger KW - Receptors, Serotonin, 5-HT2 KW - Receptors, Serotonin, 5-HT3 KW - Recombinant Proteins KW - Serotonin Antagonists KW - Serotonin Receptor Agonists KW - Thionucleotides KW - Tropanes KW - Receptor, Serotonin, 5-HT1A KW - 112692-38-3 KW - LY 278584 KW - 119193-37-2 KW - Guanosine Diphosphate KW - 146-91-8 KW - Colforsin KW - 1F7A44V6OU KW - piperazine KW - 1RTM4PAL0V KW - Serotonin KW - 333DO1RDJY KW - Spiperone KW - 4X6E73CJ0Q KW - Egtazic Acid KW - 526U7A2651 KW - guanosine 5'-O-(2-thiodiphosphate) KW - 71376-97-1 KW - N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide KW - 71IH826FEG KW - 8-Hydroxy-2-(di-n-propylamino)tetralin KW - 78950-78-4 KW - Cyclic AMP KW - E0399OZS9N KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Haloperidol KW - J6292F8L3D KW - 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid KW - K22DDW77C0 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Serotonin Receptor Agonists -- pharmacology KW - Animals KW - Drug Interactions KW - Analysis of Variance KW - Dopamine Antagonists -- pharmacology KW - Humans KW - Spiperone -- pharmacology KW - Indazoles -- pharmacology KW - Pertussis Toxin -- pharmacology KW - Oocytes -- physiology KW - Radioligand Assay KW - Potassium Channels -- drug effects KW - Piperazines -- pharmacology KW - RNA, Messenger -- biosynthesis KW - Chelating Agents -- pharmacology KW - Colforsin -- pharmacology KW - Recombinant Proteins -- metabolism KW - Haloperidol -- pharmacology KW - Oocytes -- drug effects KW - CHO Cells KW - Inhibitory Concentration 50 KW - Serotonin -- pharmacology KW - Microinjections -- methods KW - Serotonin Antagonists -- pharmacology KW - Dose-Response Relationship, Drug KW - Xenopus laevis KW - Thionucleotides -- pharmacology KW - Potassium Channels -- metabolism KW - Tropanes -- pharmacology KW - Patch-Clamp Techniques KW - 8-Hydroxy-2-(di-n-propylamino)tetralin -- pharmacology KW - Cyclic AMP -- metabolism KW - Membrane Potentials -- drug effects KW - Pyridines -- pharmacology KW - Female KW - Cricetinae KW - Egtazic Acid -- analogs & derivatives KW - Dopamine -- pharmacology KW - Receptors, Serotonin, 5-HT3 -- metabolism KW - Receptors, Serotonin, 5-HT2 -- metabolism KW - Receptors, Serotonin, 5-HT3 -- drug effects KW - Receptor, Serotonin, 5-HT1A -- metabolism KW - Guanosine Diphosphate -- analogs & derivatives KW - Receptors, Serotonin, 5-HT2 -- drug effects KW - Receptor, Serotonin, 5-HT1A -- drug effects KW - Guanosine Diphosphate -- pharmacology KW - Egtazic Acid -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71254578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Direct+activation+by+dopamine+of+recombinant+human+5-HT1A+receptors%3A+comparison+with+human+5-HT2C+and+5-HT3+receptors.&rft.au=Oz%2C+Murat%3BZhang%2C+Li%3BRotondo%2C+Alessandro%3BSun%2C+Hui%3BMorales%2C+Marisela&rft.aulast=Oz&rft.aufirst=Murat&rft.date=2003-12-15&rft.volume=50&rft.issue=4&rft.spage=303&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 - 2003-12-19 N1 - Date created - 2003-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Advances in vector-mediated gene transfer AN - 19254324; 5849283 AB - Clinical applications of gene transfer technology initially targeted the treatment of inherited monogenetic disorders and cancers refractory to conventional therapies. Today, gene transfer approaches are being developed for most tissues and for multiple disorders including those affecting quality of life. The focus herein is eventual application of gene transfer technology for the management of organ-directed autoimmunity. A specific example is presented: Sjogren's syndrome and localized salivary gland gene transfer. The status of relevant pre-clinical gene transfer studies is reviewed, with an emphasis on use of adenoviral and adeno-associated viral vectors. Current limitations of effective organ-directed gene transfer are also discussed. JF - Immunology Letters AU - Baum, B J AU - Goldsmith, C M AU - Kok, M R AU - Lodde, B M AU - van Mello, NM AU - Voutetakis, A AU - Wang, J AU - Yamano, S AU - Zheng, C AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, DHHS, Building 10, Room 1N113, MSC-1190, Bethesda, MD 20892-1190, USA, bbaum@dir.nidcr.nih.gov Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 145 EP - 149 PB - Elsevier B.V. VL - 90 IS - 2-3 SN - 0165-2478, 0165-2478 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Autoimmunity KW - Salivary gland KW - Sjogren's syndrome KW - Expression vectors KW - Gene transfer KW - Reviews KW - W3 33181:Gene therapy vectors KW - F 06780:Genetics KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19254324?accountid=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=Immunology+Letters&rft.atitle=Advances+in+vector-mediated+gene+transfer&rft.au=Baum%2C+B+J%3BGoldsmith%2C+C+M%3BKok%2C+M+R%3BLodde%2C+B+M%3Bvan+Mello%2C+NM%3BVoutetakis%2C+A%3BWang%2C+J%3BYamano%2C+S%3BZheng%2C+C&rft.aulast=Baum&rft.aufirst=B&rft.date=2003-12-15&rft.volume=90&rft.issue=2-3&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Immunology+Letters&rft.issn=01652478&rft_id=info:doi/10.1016%2Fj.imlet.2003.08.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Expression vectors; Gene transfer; Autoimmunity; Salivary gland; Sjogren's syndrome; Reviews DO - http://dx.doi.org/10.1016/j.imlet.2003.08.006 ER - TY - JOUR T1 - Maximal Oxygen Uptake and Severity of Disease in Lymphangioleiomyomatosis AN - 19229880; 5813108 AB - Lymphangioleiomyomatosis (LAM), a disease that occurs primarily in women, is characterized by cystic lung lesions causing respiratory failure, which may require lung transplantation. Lung diffusion (DL sub(CO)) and/or FEV sub(1) are decreased, but frequently not in parallel with each other. Because cardiopulmonary exercise testing (CPET) provides information that is not obtainable from resting cardiopulmonary tests, we performed CPET in 217 LAM patients and correlated exercise data with clinical markers of severity, computed tomography scans, lung function, and histology. VO sub(2)max was decreased in 162 patients, of whom 28 did not reach anaerobic threshold; 29 had low oxygen uptake at anaerobic threshold, and 54 developed hypoxemia. Hypoxemia occurred even in patients with near normal DL sub(CO) and FEV sub(1). VO sub(2)max decreased with an increasing score of histologic LAM severity and was correlated with computed tomography scans, the use of oxygen, and resting Pa sub(O[sub]2). DL sub(CO) and FEV sub(1), however, were the only significant predictors of VO sub(2)max. We conclude that CPET uncovers the presence of exercise-induced hypoxemia and assists in grading the severity of disease and determining supplemental oxygen requirements in patients with LAM. JF - American Journal of Respiratory and Critical Care Medicine AU - Taveira-DaSilva, A M AU - Stylianou, M P AU - Hedin, C J AU - Kristof, A S AU - Avila, NA AU - Rabel, A AU - Travis, W D AU - Moss, J AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 6D05, MSC 1590, Bethesda, MD 20892-1590, USA, mossj@nhlbi.nih.gov Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 1427 EP - 1431 VL - 168 IS - 12 SN - 0003-0805, 0003-0805 KW - Physical Education Index KW - Anaerobic threshold KW - Maximum oxygen consumption (women) KW - Respiration KW - Women KW - Organ transplants KW - Lungs KW - Diseases KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19229880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.atitle=Maximal+Oxygen+Uptake+and+Severity+of+Disease+in+Lymphangioleiomyomatosis&rft.au=Taveira-DaSilva%2C+A+M%3BStylianou%2C+M+P%3BHedin%2C+C+J%3BKristof%2C+A+S%3BAvila%2C+NA%3BRabel%2C+A%3BTravis%2C+W+D%3BMoss%2C+J&rft.aulast=Taveira-DaSilva&rft.aufirst=A&rft.date=2003-12-15&rft.volume=168&rft.issue=12&rft.spage=1427&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.issn=00030805&rft_id=info:doi/10.1164%2Frccm.200206-593OC LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Respiration; Lungs; Organ transplants; Diseases; Maximum oxygen consumption (women); Women; Anaerobic threshold DO - http://dx.doi.org/10.1164/rccm.200206-593OC ER - TY - JOUR T1 - Structure and Distribution of an Unusual Chimeric Genetic Element Encoding Macrolide Resistance in Phylogenetically Diverse Clones of Group A Streptococcus AN - 19225110; 5801122 AB - The resistance of group A Streptococcus (GAS) to macrolide antibiotics is now a worldwide problem. Preliminary sequencing of the genome of an erythromycin-resistant serotype M6 clone that was responsible for a pharyngitis outbreak in Pittsburgh, Pennsylvania, was conducted to determine the structure of the genetic element containing the mefA gene, which encodes a macrolide efflux protein. The mefA gene is associated with a 58.8-kb chimeric genetic element composed of a transposon inserted into a prophage. This element also encodes a putative extracellular protein with a cell-wall anchoring motif (LPKTG) located at the carboxyterminus. The mefA element was present in phylogenetically diverse GAS strains isolated throughout the United States. Culture supernatants, prepared after mitomycin C treatment, of a strain representing the outbreak clone contained mefA element DNA in a DNAse-resistant form. Together, these data provide new information about the molecular genetic basis of macrolide resistance and dissemination in GAS strains. JF - Journal of Infectious Diseases AU - Banks, D J AU - Porcella, S F AU - Barbian, K D AU - Martin, J M AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, Montana, USA Y1 - 2003/12/15/ PY - 2003 DA - 2003 Dec 15 SP - 1899 EP - 1909 VL - 188 IS - 12 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts B: Bacteriology KW - mefA gene KW - Chimeras KW - Outbreaks KW - Pharyngitis KW - Macrolide antibiotics KW - Antibiotic resistance KW - Streptococcus pyogenes KW - USA, Pennsylvania, Pittsburgh KW - J 02795:Antibiotic resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19225110?accountid=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=Fertility+and+sterility&rft.atitle=Infertility+drugs+and+the+risk+of+breast+cancer%3A+findings+from+the+National+Institute+of+Child+Health+and+Human+Development+Women%27s+Contraceptive+and+Reproductive+Experiences+Study.&rft.au=Burkman%2C+Ronald+T%3BTang%2C+Mei-Tzu+C%3BMalone%2C+Kathleen+E%3BMarchbanks%2C+Polly+A%3BMcDonald%2C+Jill+A%3BFolger%2C+Suzanne+G%3BNorman%2C+Sandra+A%3BStrom%2C+Brian+L%3BBernstein%2C+Leslie%3BUrsin%2C+Giske%3BWeiss%2C+Linda+K%3BDaling%2C+Janet+R%3BSimon%2C+Michael+S%3BSpirtas%2C+Robert&rft.aulast=Burkman&rft.aufirst=Ronald&rft.date=2003-04-01&rft.volume=79&rft.issue=4&rft.spage=844&rft.isbn=&rft.btitle=&rft.title=Fertility+and+sterility&rft.issn=00150282&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pyogenes; USA, Pennsylvania, Pittsburgh; Chimeras; Macrolide antibiotics; Antibiotic resistance; mefA gene; Pharyngitis; Outbreaks ER - TY - JOUR T1 - The efficiency and specificity of apurinic/apyrimidinic site bypass by human DNA polymerase eta and Sulfolobus solfataricus Dpo4. AN - 71441397; 14523013 AB - One of the most common DNA lesions arising in cells is an apurinic/apyrimidinic (AP) site resulting from base loss. Although a template strand AP site impedes DNA synthesis, translesion synthesis (TLS) DNA polymerases can bypass an AP site. Because this bypass is expected to be highly mutagenic because of loss of base coding potential, here we quantify the efficiency and the specificity of AP site bypass by two Y family TLS enzymes, Sulfolobus solfataricus DNA polymerase 4 (Dpo4) and human DNA polymerase eta (Pol eta). During a single cycle of processive DNA synthesis, Dpo4 and Pol eta bypass synthetic AP sites with 13-30 and 10-13%, respectively, of the bypass efficiency for undamaged bases in the same sequence contexts. These efficiencies are higher than for the A family, exonuclease-deficient Klenow fragment of Escherichia coli DNA polymerase I. We then determined AP site bypass specificity for complete bypass, requiring insertion or misalignment at the AP site followed by multiple incorporations using the aberrant primer templates. Although Dpo4, Pol eta, and Klenow polymerase have different fidelity when copying undamaged DNA, bypass of AP sites lacking A or G by all three polymerases is nearly 100% mutagenic. The majority (70-80%) of bypass events made by all three polymerases are insertion of dAMP opposite the AP site. Single base deletion errors comprise 10-25% of bypass events, with other base insertions observed at lower rates. Given that mammalian cells contain five polymerases implicated in TLS, and given that a large number of AP sites are generated per mammalian cell per day, even moderately efficient AP site bypass could be a source of substitution and frameshift mutagenesis in vivo. JF - The Journal of biological chemistry AU - Kokoska, Robert J AU - McCulloch, Scott D AU - Kunkel, Thomas A AD - Laboratories of Molecular Genetics and Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/12/12/ PY - 2003 DA - 2003 Dec 12 SP - 50537 EP - 50545 VL - 278 IS - 50 SN - 0021-9258, 0021-9258 KW - DNA KW - 9007-49-2 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Index Medicus KW - Protein Structure, Secondary KW - Escherichia coli -- metabolism KW - DNA Damage KW - Models, Molecular KW - DNA -- metabolism KW - Humans KW - Escherichia coli -- enzymology KW - Protein Binding KW - Gene Deletion KW - Frameshift Mutation KW - Microscopy, Fluorescence KW - Base Sequence KW - Models, Genetic KW - Molecular Sequence Data KW - Substrate Specificity KW - Species Specificity KW - Mutation KW - DNA Replication KW - Sulfolobus -- metabolism KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71441397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+efficiency+and+specificity+of+apurinic%2Fapyrimidinic+site+bypass+by+human+DNA+polymerase+eta+and+Sulfolobus+solfataricus+Dpo4.&rft.au=Kokoska%2C+Robert+J%3BMcCulloch%2C+Scott+D%3BKunkel%2C+Thomas+A&rft.aulast=Kokoska&rft.aufirst=Robert&rft.date=2003-12-12&rft.volume=278&rft.issue=50&rft.spage=50537&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 - 2004-01-15 N1 - Date created - 2003-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expectation enhances the regional brain metabolic and the reinforcing effects of stimulants in cocaine abusers. AN - 71471524; 14673011 AB - The reinforcing effects of drugs of abuse result from the complex interaction between pharmacological effects and conditioned responses. Here we evaluate how expectation affects the response to the stimulant drug methylphenidate in 25 cocaine abusers. The effects of methylphenidate (0.5 mg/kg, i.v.) on brain glucose metabolism (measured by [18F]deoxyglucose-positron emission tomography) and on its reinforcing effects (self-reports of drug effects) were evaluated in four conditions: (1) expecting placebo and receiving placebo; (2) expecting placebo and receiving methylphenidate; (3) expecting methylphenidate and receiving methylphenidate; (4) expecting methylphenidate and receiving placebo. Methylphenidate increased brain glucose metabolism, and the largest changes were in cerebellum, occipital cortex, and thalamus. The increases in metabolism were approximately 50% larger when methylphenidate was expected than when it was not, and these differences were significant in cerebellum (vermis) and thalamus. In contrast, unexpected methylphenidate induced greater increases in left lateral orbitofrontal cortex than when it was expected. Methylphenidate-induced increases in self-reports of "high" were also approximately 50% greater when subjects expected to receive it than when they did not and were significantly correlated with the metabolic increases in thalamus but not in cerebellum. These findings provide evidence that expectation amplifies the effects of methylphenidate in brain and its reinforcing effects. They also suggest that the thalamus, a region involved with conditioned responses, may mediate the enhancement of the reinforcing effects of methylphenidate by expectation and that the orbitofrontal cortex mediates the response to unexpected reinforcement. The enhanced cerebellar activation with expectation may reflect conditioned responses that are not linked to conscious responses. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Volkow, Nora D AU - Wang, Gene-Jack AU - Ma, Yemin AU - Fowler, Joanna S AU - Zhu, Wei AU - Maynard, Laurence AU - Telang, Frank AU - Vaska, Paul AU - Ding, Yu-Shin AU - Wong, Christopher AU - Swanson, James M AD - Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA. nvolkow@nida.nih.gov Y1 - 2003/12/10/ PY - 2003 DA - 2003 Dec 10 SP - 11461 EP - 11468 VL - 23 IS - 36 KW - Central Nervous System Stimulants KW - 0 KW - Methylphenidate KW - 207ZZ9QZ49 KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Humans KW - Glucose -- metabolism KW - Adult KW - Tomography, Emission-Computed KW - Male KW - Female KW - Central Nervous System Stimulants -- pharmacology KW - Conditioning (Psychology) KW - Methylphenidate -- pharmacology KW - Brain -- drug effects KW - Reinforcement (Psychology) KW - Cocaine-Related Disorders -- psychology KW - Brain -- metabolism KW - Cocaine-Related Disorders -- metabolism KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71471524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glutaredoxin+is+essential+for+maintenance+of+brain+mitochondrial+complex+I%3A+studies+with+MPTP.&rft.au=Kenchappa%2C+Rajappa+S%3BRavindranath%2C+Vijayalakshmi&rft.aulast=Kenchappa&rft.aufirst=Rajappa&rft.date=2003-04-01&rft.volume=17&rft.issue=6&rft.spage=717&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-16 N1 - Date created - 2003-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nickel carcinogenesis. AN - 71410334; 14643413 AB - Human exposure to highly nickel-polluted environments, such as those associated with nickel refining, electroplating, and welding, has the potential to produce a variety of pathologic effects. Among them are skin allergies, lung fibrosis, and cancer of the respiratory tract. The exact mechanisms of nickel-induced carcinogenesis are not known and have been the subject of numerous epidemiologic and experimental investigations. These mechanisms are likely to involve genetic and epigenetic routes. The present review provides evidence for the genotoxic and mutagenic activity of Ni(II) particularly at high doses. Such doses are best delivered into the cells by phagocytosis of sparingly soluble nickel-containing dust particles. Ni(II) genotoxicity may be aggravated through the generation of DNA-damaging reactive oxygen species (ROS) and the inhibition of DNA repair by this metal. Broad spectrum of epigenetic effects of nickel includes alteration in gene expression resulting from DNA hypermethylation and histone hypoacetylation, as well as activation or silencing of certain genes and transcription factors, especially those involved in cellular response to hypoxia. The investigations of the pathogenic effects of nickel greatly benefit from the understanding of the chemical basis of Ni(II) interactions with intracellular targets/ligands and oxidants. Many pathogenic effects of nickel are due to the interference with the metabolism of essential metals such as Fe(II), Mn(II), Ca(II), Zn(II), or Mg(II). Research in this field allows for identification of putative Ni(II) targets relevant to carcinogenesis and prediction of pathogenic effects caused by exposure to nickel. Ultimately, the investigations of nickel carcinogenesis should be aimed at the development of treatments that would inhibit or prevent Ni(II) interactions with critical target molecules and ions, Fe(II) in particular, and thus avert the respiratory tract cancer and other adverse health effects in nickel workers. JF - Mutation research AU - Kasprzak, Kazimierz S AU - Sunderman, F William AU - Salnikow, Konstantin AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. kasprkaz@mail.ncifcrf.gov Y1 - 2003/12/10/ PY - 2003 DA - 2003 Dec 10 SP - 67 EP - 97 VL - 533 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Air Pollutants KW - 0 KW - Carcinogens KW - Mutagens KW - Reactive Oxygen Species KW - Nickel KW - 7OV03QG267 KW - Index Medicus KW - Animals KW - DNA Damage KW - Cells, Cultured KW - Humans KW - Cell Transformation, Neoplastic KW - Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - Nickel -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71410334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nickel+carcinogenesis.&rft.au=Kasprzak%2C+Kazimierz+S%3BSunderman%2C+F+William%3BSalnikow%2C+Konstantin&rft.aulast=Kasprzak&rft.aufirst=Kazimierz&rft.date=2003-12-10&rft.volume=533&rft.issue=1-2&rft.spage=67&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 - 2004-01-12 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of a highly stable, internalizing anti-CD22 single-chain Fv fragment for targeting non-Hodgkin's lymphoma. AN - 71306078; 14566834 AB - The generation of a single chain Fv (scFv) fragment derived from the anti-CD22 monoclonal antibody LL2 resulted in a molecule with good antigen binding but very poor stability properties, thus hampering its clinical applicability. Here we report on the construction of an engineered LL2 scFv fragment by rational mutagenesis. The contribution of uncommon wild-type sequence residues for providing stability to the conserved common core structure of immunoglobulins was examined. Aided by computer homology modeling, 3 destabilizing residues within the core of the wild-type VH domain were identified. Owing to the conserved nature of the buried core structure, mutagenesis of these sites to respective consensus residues markedly stabilized the molecule but did not influence its antigen binding properties: the engineered scFv MJ-7 exhibited exceptional biophysical stability with a half-life not reached after 6 days of incubation in human serum at 37 degrees C, while fully retaining the epitope specificity of the monoclonal antibody, and antigen binding affinity of the wild-type scFv. Furthermore, both the monoclonal antibody LL2 and the engineered scFv fragment became fully internalized after only 30 min of incubation at 37 degrees C with CD22+ tumor cells. These properties predict scFv MJ-7 could become a novel powerful tool to selectively deliver cytotoxic agents to malignant CD22+ cells. Copyright 2003 Wiley-Liss, Inc. JF - International journal of cancer AU - Arndt, Michaela A E AU - Krauss, Jürgen AU - Schwarzenbacher, Robert AU - Vu, Bang K AU - Greene, Shailen AU - Rybak, Susanna M AD - National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA. Y1 - 2003/12/10/ PY - 2003 DA - 2003 Dec 10 SP - 822 EP - 829 VL - 107 IS - 5 SN - 0020-7136, 0020-7136 KW - Antigens, CD KW - 0 KW - Antigens, Differentiation, B-Lymphocyte KW - CD22 protein, human KW - Cell Adhesion Molecules KW - Immunoglobulin Fragments KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Light Chains KW - Immunoglobulin Variable Region KW - Lectins KW - Sialic Acid Binding Ig-like Lectin 2 KW - Index Medicus KW - Immunoglobulin Light Chains -- immunology KW - Immunoglobulin Heavy Chains -- immunology KW - Protein Structure, Secondary KW - Computer Simulation KW - Tumor Cells, Cultured KW - Models, Molecular KW - Kinetics KW - Humans KW - Hydrogen Bonding KW - Binding Sites, Antibody KW - Immunotherapy -- methods KW - Lymphoma, Non-Hodgkin -- therapy KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Immunoglobulin Variable Region -- immunology KW - Immunoglobulin Variable Region -- chemistry KW - Immunoglobulin Fragments -- immunology KW - Lectins -- immunology KW - Antigens, CD -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71306078?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Generation+of+a+highly+stable%2C+internalizing+anti-CD22+single-chain+Fv+fragment+for+targeting+non-Hodgkin%27s+lymphoma.&rft.au=Arndt%2C+Michaela+A+E%3BKrauss%2C+J%C3%BCrgen%3BSchwarzenbacher%2C+Robert%3BVu%2C+Bang+K%3BGreene%2C+Shailen%3BRybak%2C+Susanna+M&rft.aulast=Arndt&rft.aufirst=Michaela+A&rft.date=2003-12-10&rft.volume=107&rft.issue=5&rft.spage=822&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 - 2004-02-18 N1 - Date created - 2003-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cadmium carcinogenesis AN - 19208464; 5784949 AB - Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis. JF - Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, 111 Alexander Drive, P.O. Box 12233, Mail Drop F0-09, Triangle Park, NC 27706, USA Y1 - 2003/12/10/ PY - 2003 DA - 2003 Dec 10 SP - 107 EP - 120 PB - Elsevier B.V. VL - 533 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Toxicology Abstracts KW - Heavy metals KW - Reviews KW - Carcinogenesis KW - Cadmium KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19208464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.atitle=Cadmium+carcinogenesis&rft.au=Waalkes%2C+M+P&rft.aulast=Waalkes&rft.aufirst=M&rft.date=2003-12-10&rft.volume=533&rft.issue=1-2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.issn=00275107&rft_id=info:doi/10.1016%2Fj.mrfmmm.2003.07.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Cadmium; Heavy metals; Carcinogenesis DO - http://dx.doi.org/10.1016/j.mrfmmm.2003.07.011 ER - TY - JOUR T1 - A new reverse transcription-polymerase chain reaction method for accurate quantification. AN - 71573649; 14664723 AB - Reverse transcription-polymerase chain reaction (RT-PCR) is a very sensitive technique to measure and to compare mRNA levels among samples. However, it is extremely difficult to maintain linearity across the entire procedure, especially at the step of PCR amplification. Specific genes have been used as baseline controls to be co-amplified with target genes to normalize the amplification efficiency, but development or selection of reliable controls itself has created a new challenge. Here, we describe a new quantitative RT-PCR to compare two mRNA samples directly without the requirement of synthetic control DNAs for reference. First, chimeric RT primers carrying gene-specific and universal PCR priming sequences with or without a linker for size distinction were utilized to generate cDNAs. The size-different cDNAs were then combined in a single reaction for PCR amplification using the same primer set. The two amplified products were resolved and detected with gel electrophoresis and fluorescence imaging. Relative abundance of the two products was obtained after a baseline correction. This methodology is simple and accurate as indicated by equal amplification efficiency throughout PCR cycling. It is also easily implemented for many existing protocols. In addition, parameters affecting RT linearity are characterized in this report. JF - BMC biotechnology AU - Shiao, Yih-Horng AD - Laboratory of Comparative Carcinogenesis, Building 538, Room 205, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA. shiao@mail.ncifcrf.gov Y1 - 2003/12/09/ PY - 2003 DA - 2003 Dec 09 SP - 22 VL - 3 KW - Collagen Type I KW - 0 KW - RNA, Messenger KW - Index Medicus KW - Rats KW - Collagen Type I -- biosynthesis KW - Animals KW - Reproducibility of Results KW - Gene Expression KW - Collagen Type I -- genetics KW - Cell Line KW - Models, Theoretical KW - RNA, Messenger -- metabolism KW - RNA, Messenger -- analysis KW - Reverse Transcriptase Polymerase Chain Reaction -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71573649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+biotechnology&rft.atitle=A+new+reverse+transcription-polymerase+chain+reaction+method+for+accurate+quantification.&rft.au=Shiao%2C+Yih-Horng&rft.aulast=Shiao&rft.aufirst=Yih-Horng&rft.date=2003-12-09&rft.volume=3&rft.issue=&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=BMC+biotechnology&rft.issn=1472-6750&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-26 N1 - Date created - 2004-05-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Methods. 2001 Dec;25(4):386-401 [11846608] Biochem Biophys Res Commun. 2002 Jun 7;294(2):347-53 [12051718] Exp Hematol. 2002 Jun;30(6):503-12 [12063017] J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2002 Nov;20(2):77-116 [12515671] Mol Biotechnol. 1995 Apr;3(2):129-34 [7620973] Anal Biochem. 2002 Mar 1;302(1):52-9 [11846375] Biotechniques. 1999 Jan;26(1):112-22, 124-5 [9894600] Mol Pathol. 1999 Feb;52(1):50-1 [10439841] Cancer Res. 2000 Jun 1;60(11):2816-9 [10850420] Methods Mol Biol. 2001;160:49-63 [11265305] Clin Chem Lab Med. 1998 May;36(5):255-69 [9676381] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Translating A2A antagonist KW6002 from animal models to parkinsonian patients. AN - 71446203; 14663022 AB - Improving the translation of novel findings from basic laboratory research to better therapies for neurologic disease constitutes a major challenge for the neurosciences. This brief review of aspects of the development of an adenosine A2A antagonist for use in the management of Parkinson's disease (PD) illustrates approaches to some of the relevant issues. Adenosine A2A receptors, highly expressed on striatal medium spiny neurons, signal via kinases whose aberrant activation has been linked to the appearance of parkinsonian signs after dopaminergic denervation and to the motor response complications produced by dopaminomimetic therapy. To assess the ability of A2A receptor blockade to normalize certain of these kinases and thus benefit motor dysfunction, the palliative and prophylactic effects of the selective antagonist KW6002 were first evaluated in rodent and primate models. In hemiparkinsonian rats, KW6002 reversed the intermittent L-dopa treatment-induced, protein kinase A-mediated hyperphosphorylation of striatal alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid receptor GluR1 S845 residues and the concomitant shortening in motor response duration. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys, coadministration of KW6002 with daily apomorphine injections acted prophylactically to prevent dyskinesia onset. These and related preclinical observations guided the design of a limited, randomized, controlled, proof-of-concept study of the A2A antagonist in patients with moderately advanced PD. Although KW6002 alone or in combination with a steady-state IV infusion of optimal-dose L-dopa had no effect on parkinsonian severity, the drug potentiated the antiparkinsonian response to low-dose L-dopa with fewer dyskinesias than produced by optimal-dose L-dopa alone. KW6002 also safely prolonged the efficacy half-time of L-dopa. The results suggest that drugs capable of selectively blocking adenosine A2A receptors could confer therapeutic benefit to L-dopa-treated parkinsonian patients and warrant further evaluation in phase II studies. They also illustrate a strategy for successfully bridging a novel approach to PD therapy from an evolving research concept to pivotal clinical trials. JF - Neurology AU - Chase, T N AU - Bibbiani, F AU - Bara-Jimenez, W AU - Dimitrova, T AU - Oh-Lee, J D AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. Y1 - 2003/12/09/ PY - 2003 DA - 2003 Dec 09 SP - S107 EP - S111 VL - 61 IS - 11 Suppl 6 KW - Adenosine A2 Receptor Antagonists KW - 0 KW - Antiparkinson Agents KW - Purines KW - Receptors, AMPA KW - glutamate receptor ionotropic, AMPA 1 KW - istradefylline KW - 2GZ0LIK7T4 KW - Levodopa KW - 46627O600J KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Neurons -- metabolism KW - Macaca fascicularis KW - Dose-Response Relationship, Drug KW - Neurons -- drug effects KW - Corpus Striatum -- metabolism KW - Humans KW - Receptors, AMPA -- biosynthesis KW - Disease Models, Animal KW - Clinical Trials as Topic -- statistics & numerical data KW - Rats KW - Rats, Sprague-Dawley KW - Corpus Striatum -- drug effects KW - Levodopa -- therapeutic use KW - Motor Activity -- drug effects KW - Drug Synergism KW - Drug Evaluation, Preclinical KW - Male KW - Antiparkinson Agents -- adverse effects KW - Purines -- adverse effects KW - Parkinsonian Disorders -- chemically induced KW - Antiparkinson Agents -- therapeutic use KW - Purines -- therapeutic use KW - Parkinsonian Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71446203?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Translating+A2A+antagonist+KW6002+from+animal+models+to+parkinsonian+patients.&rft.au=Chase%2C+T+N%3BBibbiani%2C+F%3BBara-Jimenez%2C+W%3BDimitrova%2C+T%3BOh-Lee%2C+J+D&rft.aulast=Chase&rft.aufirst=T&rft.date=2003-12-09&rft.volume=61&rft.issue=11+Suppl+6&rft.spage=S107&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=1526-632X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-11 N1 - Date created - 2003-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of doxorubicin sensitivity by a novel organic compound, oxalyl bis (N-phenyl) hydroxamic acid on acetyl aminofluorene-induced preneoplastic hepatocytes. AN - 71422016; 14643023 AB - Development of biochemical modulators and application of the same with anticancer drugs is a current approach of modern cancer chemotherapy. We report the effect of two novel hydroxamic acid derivatives, viz. oxaly bis (N-phenyl) hydroxamic acid (OBPHA) and succinyl bis (N-phenyl) hydroxamic acid (SBPHA) on doxorubicin sensitivity and on P-glycoprotein (P-gp) in acetyl amino fluorene (AAF) induced preneoplastic hepatocytes in vitro. OBPHA increases doxorubicin sensitivity in AAF induced preneoplastic hepatocytes compared to normal hepatocytes. SBPHA, with an additional -CH(2)-CH(2)- group than OBPHA does not modulate the sensitivity of doxorubicin. The mechanism of action of OBPHA and SBPHA and their in vivo toxicity on male Swiss mice has been studied. OBPHA in combination with doxorubicin (i.e. OBPHA+doxorubicin) has higher antitumour activity compared to doxorubicin alone group; in consequence, OBPHA may decrease the dose related side effect of doxorubicin. JF - Cancer letters AU - Choudhuri, S K AU - Majumder, Surajit AD - Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Calcutta 700026, India. soumitra01@vsnl.net Y1 - 2003/12/08/ PY - 2003 DA - 2003 Dec 08 SP - 25 EP - 34 VL - 202 IS - 1 SN - 0304-3835, 0304-3835 KW - Antibiotics, Antineoplastic KW - 0 KW - Benzeneacetamides KW - Calcium Channel Blockers KW - Carcinogens KW - Hydroxamic Acids KW - Oxalates KW - P-Glycoprotein KW - oxalyl bis(N-phenyl)hydroxamic acid KW - Doxorubicin KW - 80168379AG KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Verapamil KW - CJ0O37KU29 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Spleen -- metabolism KW - Dose-Response Relationship, Drug KW - Glutathione -- metabolism KW - Humans KW - Carcinogens -- toxicity KW - Cell Division -- drug effects KW - Mice KW - Verapamil -- pharmacology KW - Rats KW - Drug Therapy, Combination KW - Rats, Sprague-Dawley KW - Tumor Cells, Cultured KW - Survival Rate KW - Calcium Channel Blockers -- pharmacology KW - P-Glycoprotein -- metabolism KW - Drug Synergism KW - Male KW - Hepatocytes -- drug effects KW - 2-Acetylaminofluorene -- toxicity KW - Hydroxamic Acids -- therapeutic use KW - Precancerous Conditions -- chemically induced KW - Benzeneacetamides -- therapeutic use KW - Precancerous Conditions -- drug therapy KW - Oxalates -- therapeutic use KW - Doxorubicin -- therapeutic use KW - Precancerous Conditions -- metabolism KW - Hepatocytes -- pathology KW - Hepatocytes -- metabolism KW - Antibiotics, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71422016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modulation+of+doxorubicin+sensitivity+by+a+novel+organic+compound%2C+oxalyl+bis+%28N-phenyl%29+hydroxamic+acid+on+acetyl+aminofluorene-induced+preneoplastic+hepatocytes.&rft.au=Choudhuri%2C+S+K%3BMajumder%2C+Surajit&rft.aulast=Choudhuri&rft.aufirst=S&rft.date=2003-12-08&rft.volume=202&rft.issue=1&rft.spage=25&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 - 2004-02-03 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Validated method for the simultaneous determination of Delta 9-tetrahydrocannabinol (THC), 11-hydroxy-THC and 11-nor-9-carboxy-THC in human plasma using solid phase extraction and gas chromatography-mass spectrometry with positive chemical ionization. AN - 71434548; 14630369 AB - A fully validated, highly sensitive and specific method for the extraction and quantification of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH) in plasma is presented. This method incorporates Escherichia coli beta-glucuronidase hydrolysis to cleave glucuronic acid moieties to capture total analyte concentrations, and simultaneous solid phase extraction (SPE) of the three analytes in a single eluant with separation and quantification on a bench-top positive chemical ionization (PCI) gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring (SIM) mode. Quantitation was achieved by the addition of deuterated analogues for each analyte as internal standards (IS). Limits of quantitation (LOQ) were 0.5, 0.5 and 1.0 for THC, 11-OH-THC and THCCOOH, respectively, with linearity ranging up to 50 ng/ml for THC and 11-OH-THC, and 100 ng/ml for THCCOOH. Absolute recoveries ranged from 67.3 to 83.5% for all three analytes. Intra-assay accuracy and precision ranged from 1.2 to 12.2 and 1.4 to 4.7%, respectively. Inter-assay accuracy and precision ranged from 1.4 to 12.2 and 3.1 to 7.3%, respectively. This method was used to analyze plasma samples collected from individuals participating in a controlled oral THC administration study. Statistically significant (P< or =0.05) increases of 40% for 11-OH-THC and 42% for THCCOOH concentrations were found between hydrolyzed and non-hydrolyzed results. This method will be utilized in ongoing controlled cannabinoid administration studies and may be a useful analytical procedure for the fields of forensic toxicology and cannabinoid pharmacology. JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences AU - Gustafson, Richard A AU - Moolchan, Eric T AU - Barnes, Allan AU - Levine, Barry AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003/12/05/ PY - 2003 DA - 2003 Dec 05 SP - 145 EP - 154 VL - 798 IS - 1 SN - 1570-0232, 1570-0232 KW - 11-hydroxy-delta(9)-tetrahydrocannabinol KW - 26108-40-7 KW - 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid KW - 4TPC9E4A32 KW - Dronabinol KW - 7J8897W37S KW - Index Medicus KW - Sensitivity and Specificity KW - Reproducibility of Results KW - Humans KW - Dronabinol -- analogs & derivatives KW - Gas Chromatography-Mass Spectrometry -- methods KW - Dronabinol -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71434548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chromatography.+B%2C+Analytical+technologies+in+the+biomedical+and+life+sciences&rft.atitle=Validated+method+for+the+simultaneous+determination+of+Delta+9-tetrahydrocannabinol+%28THC%29%2C+11-hydroxy-THC+and+11-nor-9-carboxy-THC+in+human+plasma+using+solid+phase+extraction+and+gas+chromatography-mass+spectrometry+with+positive+chemical+ionization.&rft.au=Gustafson%2C+Richard+A%3BMoolchan%2C+Eric+T%3BBarnes%2C+Allan%3BLevine%2C+Barry%3BHuestis%2C+Marilyn+A&rft.aulast=Gustafson&rft.aufirst=Richard&rft.date=2003-12-05&rft.volume=798&rft.issue=1&rft.spage=145&rft.isbn=&rft.btitle=&rft.title=Journal+of+chromatography.+B%2C+Analytical+technologies+in+the+biomedical+and+life+sciences&rft.issn=15700232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-19 N1 - Date created - 2003-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel insights into M5 muscarinic acetylcholine receptor function by the use of gene targeting technology. AN - 71357557; 14607263 AB - Until recently, little was known about the possible physiological functions of the M(5) muscarinic acetylcholine receptor subtype, the last member of the muscarinic receptor family (M(1)-M(5)) to be cloned. To learn more about the potential physiological roles of this receptor subtype, we generated and analyzed M(5) receptor-deficient mice (M5 -/- mice). Strikingly, acetylcholine, a potent dilator of most vascular beds, virtually lost the ability to dilate cerebral arteries and arterioles in M5 -/- mice, suggesting that endothelial M(5) receptors mediate this activity in wild-type mice. This effect was specific for cerebral blood vessels, since acetylcholine-mediated dilation of extra-cerebral arteries remained fully intact in M5 -/- mice. In addition, in vitro neurotransmitter release experiments indicated that M(5) receptors located on dopaminergic nerve terminals play a role in facilitating muscarinic agonist-induced dopamine release in the striatum, consistent with the observation that the dopaminergic neurons innervating the striatum almost exclusively express the M(5) receptor subtype. We also found that the rewarding effects of morphine, the prototypical opiate analgesic, were substantially reduced in M5 -/- mice, as measured in the conditioned place preference paradigm. Furthermore, both the somatic and affective components of naloxone-induced morphine withdrawal symptoms were significantly attenuated in M5 -/- mice. It is likely that these behavioral deficits are caused by the lack of mesolimbic M(5) receptors, activation of which is known to stimulate dopamine release in the nucleus accumbens. These results convincingly demonstrate that the M(5) muscarinic receptor is involved in modulating several important pharmacological and behavioral functions. These findings may lead to novel therapeutic strategies for the treatment of drug addiction and certain cerebrovascular disorders. JF - Life sciences AU - Yamada, Masahisa AU - Basile, Anthony S AU - Fedorova, Irina AU - Zhang, Weilie AU - Duttaroy, Alokesh AU - Cui, Yinghong AU - Lamping, Kathryn G AU - Faraci, Frank M AU - Deng, Chu Xia AU - Wess, Jürgen AD - Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg. 8A, Room B1A-05, 8 Center Drive MSC 0810, Bethesda, MD 20892-0810, USA. Y1 - 2003/12/05/ PY - 2003 DA - 2003 Dec 05 SP - 345 EP - 353 VL - 74 IS - 2-3 SN - 0024-3205, 0024-3205 KW - Analgesics, Opioid KW - 0 KW - Receptor, Muscarinic M5 KW - Morphine KW - 76I7G6D29C KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Conditioning, Operant -- drug effects KW - Animals KW - Substance Withdrawal Syndrome -- physiopathology KW - Vasodilation -- physiology KW - Dopamine -- metabolism KW - Mice KW - Mice, Knockout KW - Morphine -- pharmacology KW - Rats KW - Parasympathetic Nervous System -- physiology KW - Neostriatum -- metabolism KW - Reward KW - Analgesics, Opioid -- pharmacology KW - Brain Chemistry -- genetics KW - Substance Withdrawal Syndrome -- genetics KW - Gene Targeting KW - Brain Chemistry -- physiology KW - Receptor, Muscarinic M5 -- physiology KW - Receptor, Muscarinic M5 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71357557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Prevalence+and+correlates+of+areca+nut+use+among+psychiatric+patients+in+India.&rft.au=Chandra%2C+Prabha+S%3BCarey%2C+Michael+P%3BCarey%2C+Kate+B%3BJairam%2C+K+R&rft.aulast=Chandra&rft.aufirst=Prabha&rft.date=2003-04-01&rft.volume=69&rft.issue=3&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-05 N1 - Date created - 2003-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Survival after pancreas transplantation in patients with diabetes and preserved kidney function. AN - 71441921; 14657065 AB - Solitary pancreas transplantation (ie, pancreas alone or pancreas-after-kidney) for diabetes mellitus remains controversial due to procedure-associated morbidity/mortality, toxicity of immunosuppression, expense, and unproven effects on the secondary complications of diabetes. Whether transplantation offers a survival advantage over conventional therapies for diabetes is unknown. To determine the association between solitary pancreas transplantation and survival in patients with diabetes and preserved kidney function. Retrospective observational cohort study conducted at 124 transplant centers in the United States, in 11 572 patients with diabetes mellitus on the waiting list for pancreas transplantation (pancreas alone, pancreas-after-kidney, or simultaneous pancreas-kidney) at the United Network for Organ Sharing/Organ Procurement and Transplantation Network between January 1, 1995, and December 31, 2000. All patients receiving a multiorgan (other than simultaneous pancreas-kidney) transplant were excluded, as were those listed for solitary pancreas transplantation who had a serum creatinine level greater than 2 mg/dL (176.8 micromol/L) at time of listing, or who ultimately received a simultaneous pancreas-kidney transplant. All-cause mortality within 4 years following transplantation (or within a comparable time on the waiting list for the group not undergoing transplantation). Overall relative risk of all-cause mortality for transplant recipients (compared with patients awaiting the same procedure) over 4 years of follow-up was 1.57 (95% confidence interval [CI], 0.98-2.53; P =.06) for pancreas transplant alone, 1.42 (95% CI, 1.03-1.94; P =.03) for pancreas-after-kidney transplant, and 0.43 (95% CI, 0.39-0.48) for simultaneous pancreas-kidney transplant. Transplant patient 1- and 4-year survival rates were 96.5% and 85.2% for pancreas transplant alone, respectively, and 95.3% and 84.5% for pancreas-after-kidney transplant, while 1- and 4-year survival rates for patients on the waiting list were 97.6% and 92.1% for pancreas transplant alone, respectively, and 97.1% and 88.1% for pancreas-after-kidney transplant. From 1995-2000, survival for those with diabetes and preserved kidney function and receiving a solitary pancreas transplant was significantly worse compared with the survival of waiting-list patients receiving conventional therapy. JF - JAMA AU - Venstrom, Jeffrey M AU - McBride, Maureen A AU - Rother, Kristina I AU - Hirshberg, Boaz AU - Orchard, Trevor J AU - Harlan, David M AD - Transplantation and Autoimmunity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Md 20892, USA. Y1 - 2003/12/03/ PY - 2003 DA - 2003 Dec 03 SP - 2817 EP - 2823 VL - 290 IS - 21 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Adult KW - Retrospective Studies KW - Prognosis KW - Waiting Lists KW - Middle Aged KW - Child KW - Adolescent KW - Male KW - Female KW - Survival Analysis KW - Proportional Hazards Models KW - Diabetes Mellitus -- surgery KW - Diabetes Mellitus -- mortality KW - Pancreas Transplantation -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71441921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Survival+after+pancreas+transplantation+in+patients+with+diabetes+and+preserved+kidney+function.&rft.au=Venstrom%2C+Jeffrey+M%3BMcBride%2C+Maureen+A%3BRother%2C+Kristina+I%3BHirshberg%2C+Boaz%3BOrchard%2C+Trevor+J%3BHarlan%2C+David+M&rft.aulast=Venstrom&rft.aufirst=Jeffrey&rft.date=2003-12-03&rft.volume=290&rft.issue=21&rft.spage=2817&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=1538-3598&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-11 N1 - Date created - 2003-12-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 2003 Dec 3;290(21):2861-3 [14657072] JAMA. 2005 Feb 9;293(6):675; author reply 675-6 [15701906] Curr Surg. 2005 May-Jun;62(3):305-10 [15890213] Erratum In: JAMA. 2004 Apr 7;291(13):1566 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hodgkin's lymphoma: a case report involving the mandible. AN - 85370255; pmid-14663818 JF - Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons AU - Warburton, Gary AU - Childs, Richard C AU - Charles, Makepeace AU - Brahim, Jaime S AD - National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 1492 EP - 1496 VL - 61 IS - 12 SN - 0278-2391, 0278-2391 KW - National Library of Medicine KW - Adult KW - Female KW - *Hodgkin Disease: diagnosis KW - Hodgkin Disease: pathology KW - Hodgkin Disease: therapy KW - Humans KW - *Mandibular Diseases: diagnosis KW - Mandibular Diseases: pathology KW - Mandibular Diseases: therapy KW - *Mandibular Neoplasms: diagnosis KW - Mandibular Neoplasms: pathology KW - Mandibular Neoplasms: therapy KW - Recurrence KW - Treatment Outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85370255?accountid=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+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.atitle=Hodgkin%27s+lymphoma%3A+a+case+report+involving+the+mandible.&rft.au=Warburton%2C+Gary%3BChilds%2C+Richard+C%3BCharles%2C+Makepeace%3BBrahim%2C+Jaime+S&rft.aulast=Warburton&rft.aufirst=Gary&rft.date=2003-12-01&rft.volume=61&rft.issue=12&rft.spage=1492&rft.isbn=&rft.btitle=&rft.title=Journal+of+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.issn=02782391&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Audiologic manifestations of patients with post-treatment Lyme disease syndrome. AN - 85368662; pmid-14663350 AB - The purpose of this study was to characterize auditory function in patients diagnosed with post-treatment Lyme disease syndrome (PTLDS).Eighteen patients with PTLDS were evaluated and compared to a normal population. Evaluations consisted of pure tone and speech thresholds, word recognition (WRS), acoustic immittance battery, auditory brain stem response (ABR), and loudness discomfort level (LDL). Both seropositive and seronegative patients were evaluated. Audiologists were blinded to patient status.Forty four percent of the patients had one or more abnormal pure tone thresholds compared to gender- and age-adjusted norms. Thirty-one percent showed abnormally reduced LDLs, and 17% had abnormal acoustic reflexes at one or more frequencies.This paper catalogs previously unstudied long-term auditory system sequelae resulting from PTLDS. Our most significant finding was the dramatically reduced loudness tolerance in the presence of either normal or minimally impaired hearing. The clinician is encouraged to consider PTLDS when confronted with these or similar findings in patients having history of Borrelia burgdorferi infection and continued complaints. JF - Ear and hearing AU - Shotland, Lawrence I AU - Mastrioanni, Mary Ann AU - Choo, Daniel L AU - Szymko-Bennett, Yvonne M AU - Dally, Leonard G AU - Pikus, Anita T AU - Sledjeski, Kathryn AU - Marques, Adriana AD - Hearing Section, Neuro-Otology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA. Larry.Shotland@med.va.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 508 EP - 517 VL - 24 IS - 6 SN - 0196-0202, 0196-0202 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Audiometry, Pure-Tone KW - Audiometry, Speech KW - *Auditory Perceptual Disorders: etiology KW - Auditory Threshold KW - Chronic Disease KW - Evoked Potentials, Auditory, Brain Stem KW - Female KW - Humans KW - *Loudness Perception KW - *Lyme Disease: complications KW - Lyme Disease: drug therapy KW - Magnetic Resonance Imaging KW - Male KW - Middle Aged UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85368662?accountid=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=Ear+and+hearing&rft.atitle=Audiologic+manifestations+of+patients+with+post-treatment+Lyme+disease+syndrome.&rft.au=Shotland%2C+Lawrence+I%3BMastrioanni%2C+Mary+Ann%3BChoo%2C+Daniel+L%3BSzymko-Bennett%2C+Yvonne+M%3BDally%2C+Leonard+G%3BPikus%2C+Anita+T%3BSledjeski%2C+Kathryn%3BMarques%2C+Adriana&rft.aulast=Shotland&rft.aufirst=Lawrence&rft.date=2003-12-01&rft.volume=24&rft.issue=6&rft.spage=508&rft.isbn=&rft.btitle=&rft.title=Ear+and+hearing&rft.issn=01960202&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - High-dose fenfluramine administration decreases serotonin transporter binding, but not serotonin transporter protein levels, in rat forebrain. AN - 75720503; 14515341 AB - Administration of D-fenfluramine (D-FEN) or parachloroamphetamine (PCA) can produce long-lasting decreases in serotonin transporter (SERT) binding and tissue levels of serotonin (5-HT) in rat forebrain. These changes have been viewed as evidence for 5-HT neurotoxicity, but no studies have measured SERT protein levels. In the present study, we determined the effect of high-dose D-FEN or PCA, administered according to a "neurotoxic" dosing regimen, on the density of SERT sites using ligand binding methods and on SERT protein levels using Western blots. Rats were sacrificed 2 days and 2 weeks after administration of drug or saline. The density of SERT was determined in homogenates of caudate and whole brain minus caudate. D-FEN and PCA decreased SERT binding by 30-60% in both tissues and at both time points. Similarly, D-FEN and PCA administration profoundly decreased tissue 5-HT and 5-HIAA in frontal cortex. Despite the large decreases in SERT binding and depletion of tissue 5-HT that occurred with D-FEN administration, SERT protein expression, as determined by Western blot analysis, did not change in either tissue or time point. PCA administration decreased SERT protein by about 20% only at the 2-day point in the caudate. Drug treatments did not change expression of glial fibrillary acidic protein (GFAP), a hallmark indicator of neuronal damage, in whole brain minus caudate in the 2-week group. These results support the hypothesis that decreases in tissue 5-HT and SERT binding sites induced by D-FEN and PCA reflect neuroadaptive changes, rather than neurotoxic effects. JF - Synapse (New York, N.Y.) AU - Rothman, Richard B AU - Jayanthi, Subramaniam AU - Wang, Xiaoying AU - Dersch, Christina M AU - Cadet, Jean L AU - Prisinzano, Thomas AU - Rice, Kenner C AU - Baumann, Michael H AD - Clinical Psychopharmacology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. rrothman@intra.nida.nih.gov Y1 - 2003/12/01/ PY - 2003 DA - 2003 Dec 01 SP - 233 EP - 239 VL - 50 IS - 3 SN - 0887-4476, 0887-4476 KW - Carrier Proteins KW - 0 KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Serotonin Agents KW - Serotonin Plasma Membrane Transport Proteins KW - Slc6a4 protein, rat KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - p-Chloroamphetamine KW - 64-12-0 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Hydroxyindoleacetic Acid -- metabolism KW - Male KW - Membrane Glycoproteins -- drug effects KW - Carrier Proteins -- metabolism KW - p-Chloroamphetamine -- administration & dosage KW - Prosencephalon -- metabolism KW - p-Chloroamphetamine -- toxicity KW - Fenfluramine -- administration & dosage KW - Fenfluramine -- toxicity KW - Carrier Proteins -- drug effects KW - Serotonin Agents -- administration & dosage KW - Prosencephalon -- drug effects KW - Serotonin Agents -- toxicity KW - Serotonin -- metabolism KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75720503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High-dose+fenfluramine+administration+decreases+serotonin+transporter+binding%2C+but+not+serotonin+transporter+protein+levels%2C+in+rat+forebrain.&rft.au=Rothman%2C+Richard+B%3BJayanthi%2C+Subramaniam%3BWang%2C+Xiaoying%3BDersch%2C+Christina+M%3BCadet%2C+Jean+L%3BPrisinzano%2C+Thomas%3BRice%2C+Kenner+C%3BBaumann%2C+Michael+H&rft.aulast=Rothman&rft.aufirst=Richard&rft.date=2003-12-01&rft.volume=50&rft.issue=3&rft.spage=233&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 - 2004-01-06 N1 - Date created - 2003-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Doxorubicin in isolation limb perfusion in the treatment of advanced limb soft tissue sarcoma. AN - 71614348; 16767912 AB - Hyperthermic antiblastic perfusion/HAP) has been proven to be an effective neoadjuvant treatment in the treatment of advanced soft tissue limb sarcoma. As a matter of fact high percentage of limb sparing surgery, local control and functional results have been obtained wide this technique. Many antineoplastic drugs have been associated to hyperthermia by isolation limb perfusion, the aim of this paper was to describe the results obtained with doxorubicin in association to hyperthermia with or without Tumor Necrosis Factor (TNF) alpha in order to identify the most effective regimen in the multidisciplinary treatment of soft tissue limb sarcoma. A total of 106 patients have been evaluated. Three different study were performed: the first was a phase I study carried out in order to assess the maximum tolerable dose (MTD) of doxorubicin during HAP; the second was a phase II study with doxorubicin, and the third was a phase I - II study aimed at evaluating the MTD and tumor response of TNF alpha in association to doxorubicin and hyperthermia. Grade IV limb toxicity was recorded in 11 patients ( 4 in trial A, 3 in trial B, and 4 in trial C). The grade of limb reaction was strictly related to TNF dosage (> 1 mg) and temperature level (> 41.5 degrees C), therefore the best regimen is represented by temperature level not exceeding 41.5 degrees C and 1 mg of TNFalpha. The trimodality association (TNF, doxorubicin and hyperthermia) was proven to be the best regimen able to obtain a 77% of objective response (complete response, 22%) and a 77% of limb sparing in patients candidate to amputation. The results above mentioned showed the HAP with doxorubicin and TNFalpha (1 mg) is a very effective neoadjuvant treatment in the multidisciplinary treatment of advanced soft tissue limb sarcoma. JF - Journal of experimental & clinical cancer research : CR AU - Di Filippo, F AU - Garinei, R AU - Anzà, M AU - Cavaliere, F AU - Giannarelli, D AU - Cagol, P P AU - Rossi, C R AU - Santinami, M AU - Deraco, M AU - Botti, C AU - Perri, P AU - Di Filippo, S AU - Piarulli, L AU - Bruno, P AD - Department of Surgery, Regina Elena National Cancer Institute, Rome Italy. difilippo@ifo.it Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 81 EP - 87 VL - 22 IS - 4 Suppl SN - 0392-9078, 0392-9078 KW - Antibiotics, Antineoplastic KW - 0 KW - Tumor Necrosis Factor-alpha KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Disease-Free Survival KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Sex Factors KW - Dose-Response Relationship, Drug KW - Humans KW - Neoadjuvant Therapy KW - Aged KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Extremities -- pathology KW - Adult KW - Middle Aged KW - Maximum Tolerated Dose KW - Adolescent KW - Female KW - Male KW - Antibiotics, Antineoplastic -- administration & dosage KW - Soft Tissue Neoplasms -- mortality KW - Sarcoma -- mortality KW - Chemotherapy, Cancer, Regional Perfusion KW - Hyperthermia, Induced KW - Soft Tissue Neoplasms -- drug therapy KW - Doxorubicin -- administration & dosage KW - Sarcoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71614348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Doxorubicin+in+isolation+limb+perfusion+in+the+treatment+of+advanced+limb+soft+tissue+sarcoma.&rft.au=Di+Filippo%2C+F%3BGarinei%2C+R%3BAnz%C3%A0%2C+M%3BCavaliere%2C+F%3BGiannarelli%2C+D%3BCagol%2C+P+P%3BRossi%2C+C+R%3BSantinami%2C+M%3BDeraco%2C+M%3BBotti%2C+C%3BPerri%2C+P%3BDi+Filippo%2C+S%3BPiarulli%2C+L%3BBruno%2C+P&rft.aulast=Di+Filippo&rft.aufirst=F&rft.date=2003-12-01&rft.volume=22&rft.issue=4+Suppl&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-08-09 N1 - Date created - 2006-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hyperthermic antiblastic perfusion with TNFalpha and melphalan in stage III limb melanoma patients: A phase I - II SITILO study. AN - 71612315; 16767914 AB - Hyperthermic antiblastic perfusion (HAP) has been proven to be an effective treatment of loco-regional spreading limb melanoma. The mean complete response (CR) rate obtained is 54%, with an objective responses (OR) rate ranging between 70% and 100%. Recently, Tumor Necrosis Factor (TNFalpha) has been employed at high dosages (3-4 mg) in association to Melphalan and hyperthermia. This trimodality combination increased the percentage of CR (70%-90%), but systemic toxicity was also reported due to high TNF doses. A phase I - II study was undertaken in order to assess the MTD of TNFalpha in association to true hyperthermia (41.5 degrees C) and Melphalan. Twenty patients affected with stages IIIA (9 patients), IIIAB (10 patients), and IV (1 patient) were enrolled in this study. The trimodality treatment did not increase the local and systemic toxicity. CR was observed in 70% of the patients, PR in 20% with on OR rate of 90%. These figures are overlapping those obtained with high TNF dosages. No correlation was observed between tumor responses and TNF doses. Taking into account that 70% of our patients have been treated with TNF dosages between 0.5 mg on 1.6 mg, we conclude that 1 mg is the best dosage to be applied during HAP. Patients with bulky tumor are the best candidate to TNF perfusion, because no differences have been observed in terms of CR in patients with low tumor burden treated with TNF-Melphalan-hyperthermia or Melphalan-hyperthermia. JF - Journal of experimental & clinical cancer research : CR AU - Di Filippo, F AU - Rossi, C R AU - Garinei, R AU - Anzà, M AU - Cavaliere, F AU - Botti, C AU - Perri, P AU - Di Filippo, S AU - Di Angelo, P AU - Principi, F AU - Laurenzi, L AD - Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy. difilippo@ifo.it Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 97 EP - 101 VL - 22 IS - 4 Suppl SN - 0392-9078, 0392-9078 KW - Tumor Necrosis Factor-alpha KW - 0 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Combined Modality Therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Tumor Necrosis Factor-alpha -- adverse effects KW - Extremities -- pathology KW - Melphalan -- administration & dosage KW - Adult KW - Melphalan -- adverse effects KW - Middle Aged KW - Maximum Tolerated Dose KW - Female KW - Male KW - Survival Analysis KW - Melanoma -- mortality KW - Melanoma -- drug therapy KW - Hyperthermia, Induced -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Chemotherapy, Cancer, Regional Perfusion -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71612315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Issues+in+Molecular+Biology&rft.atitle=Handling+of+Clinical+Tissue+Specimens+for+Molecular+Profiling+Studies&rft.au=Leiva%2C+I+M%3BEmmert-Buck%2C+M+R%3BGillespie%2C+J+W&rft.aulast=Leiva&rft.aufirst=I&rft.date=2003-04-01&rft.volume=5&rft.issue=2&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Current+Issues+in+Molecular+Biology&rft.issn=14673037&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-08-09 N1 - Date created - 2006-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hyperthermic antiblastic perfusion in the treatment of locoregional spreading limb melanoma. AN - 71612272; 16767913 AB - On the basis of personal experience and a review of the literature, the authors have evaluated the results obtained with hyperthermic antiblastic perfusion (HAP) for the treatment of stage II, III and IIIAB limb melanoma. The evaluation showed that today HAP may be considered a safe and effective treatment, with a major complication rate ranging between 1% and 4%. In terms of tumor response, locoregional control and survival, this treatment has provided better results than other regional chemotherapeutic modalities and undoubtedly better results than those obtained with conventional, even radical, surgery. The multivariate analysis showed that, of the treatment-related prognostic factors, the minimum tumor temperature influenced the percentage of complete response (CR) to the greatest extent (P<0.03), with a positive trend also with regard to the dosage of the antiblastic drug employed (P<0.08). In turn, the complete response rate was a determinant as far as locoregional control (50%; P<0.0009) and disease-free (51.4%; P=0.0009) and overall survival (63%; P<0.009) rates were concerned. Of the tumor-related prognostic factors, the number of lesions (P<0.0014), sex (P<0.04), and the number of disease recurrences (P<0.01) appear to influence overall survival. JF - Journal of experimental & clinical cancer research : CR AU - Di Filippo, F AU - Garinei, R AU - Giannarelli, D AU - Anzà, M AU - Cavaliere, F AU - Botti, C AU - Perri, P AU - Di Filippo, S AU - Psaila, A AU - Callopoli, A AU - Maialetti, R AU - Sega, F AU - Frezza, F AU - Viticci, C AD - Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy. difilippo@ifo.it Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 89 EP - 95 VL - 22 IS - 4 Suppl SN - 0392-9078, 0392-9078 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Extremities -- pathology KW - Disease-Free Survival KW - Combined Modality Therapy KW - Melphalan -- administration & dosage KW - Humans KW - Clinical Trials as Topic KW - Survival Analysis KW - Melanoma -- mortality KW - Melanoma -- secondary KW - Chemotherapy, Cancer, Regional Perfusion KW - Hyperthermia, Induced KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Melanoma -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71612272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Hyperthermic+antiblastic+perfusion+in+the+treatment+of+locoregional+spreading+limb+melanoma.&rft.au=Di+Filippo%2C+F%3BGarinei%2C+R%3BGiannarelli%2C+D%3BAnz%C3%A0%2C+M%3BCavaliere%2C+F%3BBotti%2C+C%3BPerri%2C+P%3BDi+Filippo%2C+S%3BPsaila%2C+A%3BCallopoli%2C+A%3BMaialetti%2C+R%3BSega%2C+F%3BFrezza%2C+F%3BViticci%2C+C&rft.aulast=Di+Filippo&rft.aufirst=F&rft.date=2003-12-01&rft.volume=22&rft.issue=4+Suppl&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-08-09 N1 - Date created - 2006-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytoreductive surgery followed by intra peritoneal hyperthermic perfusion in the treatment of peritoneal surface malignancies: morbidity and mortality with closed abdomen technique. AN - 71611304; 16767933 AB - The purpose of this phase II study was to analyze the morbidity and mortality of cytoreductive surgery (CRS) + intraperitoneal hyperthermic perfusion (IPHP) in the treatment of peritoneal surface malignancies. One hundred and sixty four patients (36 ovarian cancer, 32 abdominal sarcomatosis, 34 peritoneal mesothelioma, 36 pseudomyxoma peritonei, 12 gastric cancer, 8 colon adenocarcinoma and 8 from other origins) underwent 166 procedures. Two patients underwent the intervention twice due to disease relapse. The mean follow-up was 20.6 months (range: 0.4 - 91.3). The mean age was 52 years (range: 24-76). CRS was performed with peritonectomy procedures. IPHP through Closed abdominal technique was conducted with preheated (42.5 degrees) perfusate containing cisplatin+mitomycin C or cisplatin+doxorubicin for 60/90 minutes. grade 3/4 morbidity rate was 12.0%. Some frequent post-operatory complications were intestinal fistulas (17), respiratory (5) and abdominal bleeding (4). Multivariate analysis with logistic regression model with the backward elimination method identified carcinomatosis extension (OR: 5.3, CI95%: 1.2-24.5) as the best predictor of morbidity grade 3/4. Four patients presented grade 3/4 toxicity. Operative mortality rate was 0.6%. CRS+ IPHP presented acceptable morbidity 3/4 toxicity and mortality rates what support the need to be tested in prospective phase III clinical trial. JF - Journal of experimental & clinical cancer research : CR AU - Kusamura, S AU - Deraco, M AU - Baratti, D AU - Inglese, M G AU - Costanzo, P AU - Favaro, M AU - Manzi, R AU - Gavazzi, C AD - Department of Surgery, Melanoma and Sarcoma Unit, National Cancer Institute of Milan. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 207 EP - 212 VL - 22 IS - 4 Suppl SN - 0392-9078, 0392-9078 KW - Doxorubicin KW - 80168379AG KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Doxorubicin -- adverse effects KW - Combined Modality Therapy KW - Risk Factors KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Doxorubicin -- administration & dosage KW - Cisplatin -- adverse effects KW - Male KW - Female KW - Cisplatin -- administration & dosage KW - Hyperthermia, Induced -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Chemotherapy, Cancer, Regional Perfusion -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Peritoneal Neoplasms -- therapy KW - Peritoneal Neoplasms -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71611304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Cytoreductive+surgery+followed+by+intra+peritoneal+hyperthermic+perfusion+in+the+treatment+of+peritoneal+surface+malignancies%3A+morbidity+and+mortality+with+closed+abdomen+technique.&rft.au=Kusamura%2C+S%3BDeraco%2C+M%3BBaratti%2C+D%3BInglese%2C+M+G%3BCostanzo%2C+P%3BFavaro%2C+M%3BManzi%2C+R%3BGavazzi%2C+C&rft.aulast=Kusamura&rft.aufirst=S&rft.date=2003-12-01&rft.volume=22&rft.issue=4+Suppl&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-08-09 N1 - Date created - 2006-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Self-report and biochemical measures of alcohol consumption. AN - 71560921; 14984236 JF - Addiction (Abingdon, England) AU - Litten, Raye Z AU - Fertig, Joanne AD - Division of Treatment and Recovery Research, National Institute of Alcohol Abuse and Alcoholism, Bethedsa, MD, USA. rlitten@willco.niaaa.nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - iii EP - iv VL - 98 Suppl 2 SN - 0965-2140, 0965-2140 KW - Biomarkers KW - 0 KW - Index Medicus KW - Humans KW - Biomarkers -- analysis KW - Self Disclosure KW - Alcoholism -- diagnosis KW - Alcohol Drinking UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71560921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Self-report+and+biochemical+measures+of+alcohol+consumption.&rft.au=Litten%2C+Raye+Z%3BFertig%2C+Joanne&rft.aulast=Litten&rft.aufirst=Raye&rft.date=2003-12-01&rft.volume=98+Suppl+2&rft.issue=&rft.spage=iii&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 - 2004-04-02 N1 - Date created - 2004-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - General principles of asthma management: environmental control. AN - 71529090; 14763364 AB - Environmental control is one of the major goals of asthma management. House dust mite environmental control and the reduction of other indoor environmental allergen triggers, such as animal dander, cockroaches, and mold spores, are important for individuals with asthma. Patients who have sensitivities to the allergens they produce should receive advice on environmental control reduction measures to prevent asthma symptoms. Nurses are in a key position to make proper environmental control recommendations to patients. JF - The Nursing clinics of North America AU - Huss, Karen AU - Travis, Patricia AU - Huss, Richard W AD - Johns Hopkins University, School of Nursing, 525 North Wolfe Street, Room 416, Baltimore, MD 21205, USA. hussk@mail.nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 609 EP - 620 VL - 38 IS - 4 SN - 0029-6465, 0029-6465 KW - Allergens KW - 0 KW - Dust KW - Abridged Index Medicus KW - Index Medicus KW - Nursing KW - Animals KW - Air Pollution, Indoor -- adverse effects KW - Patient Education as Topic -- methods KW - Humans KW - Mites KW - Laundering -- methods KW - Nurse's Role KW - Bedding and Linens -- adverse effects KW - Allergens -- adverse effects KW - Asthma -- etiology KW - Asthma -- prevention & control KW - Asthma -- nursing KW - Environmental Monitoring -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71529090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Nursing+clinics+of+North+America&rft.atitle=General+principles+of+asthma+management%3A+environmental+control.&rft.au=Huss%2C+Karen%3BTravis%2C+Patricia%3BHuss%2C+Richard+W&rft.aulast=Huss&rft.aufirst=Karen&rft.date=2003-12-01&rft.volume=38&rft.issue=4&rft.spage=609&rft.isbn=&rft.btitle=&rft.title=The+Nursing+clinics+of+North+America&rft.issn=00296465&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-04 N1 - Date created - 2004-02-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene targeting by triple helix-forming oligonucleotides. AN - 71519632; 14751832 AB - Effective gene targeting reagents would have widespread utility for genomic manipulation including transgenic cell and animal construction and for gene therapy. They would also be useful in basic research as probes of chromatin structure, and as tools for studying the repair and mutagenesis of targeted DNA damage. We are developing triple helix-forming oligonucleotides (TFOs) for gene targeting in living mammalian cells. Challenges to TFO bioactivity include the impediments to the biochemistry of triplex formation presented by the physiological environment and the charge repulsion between the duplex and the third strand. In addition, there are biological constraints to target access imposed by mammalian chromatin structure. Here we describe the oligonucleotide modification format that appears to support biological activity of TFOs. In addition we show that manipulation of the cell biology, specifically the cell cycle, has a dramatic influence on TFO bioactivity. JF - Annals of the New York Academy of Sciences AU - Majumdar, Alokes AU - Puri, Nitin AU - McCollum, Nicholas AU - Richards, Sally AU - Cuenoud, Bernard AU - Miller, Paul AU - Seidman, Michael M AD - Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 141 EP - 153 VL - 1002 SN - 0077-8923, 0077-8923 KW - Cross-Linking Reagents KW - 0 KW - Genetic Markers KW - Oligodeoxyribonucleotides KW - DNA KW - 9007-49-2 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Index Medicus KW - Animals KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Humans KW - Cross-Linking Reagents -- pharmacology KW - Cell Cycle -- physiology KW - Hypoxanthine Phosphoribosyltransferase -- metabolism KW - Oligodeoxyribonucleotides -- pharmacology KW - Gene Targeting KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71519632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+targeting+by+triple+helix-forming+oligonucleotides.&rft.au=Majumdar%2C+Alokes%3BPuri%2C+Nitin%3BMcCollum%2C+Nicholas%3BRichards%2C+Sally%3BCuenoud%2C+Bernard%3BMiller%2C+Paul%3BSeidman%2C+Michael+M&rft.aulast=Majumdar&rft.aufirst=Alokes&rft.date=2003-12-01&rft.volume=1002&rft.issue=&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-24 N1 - Date created - 2004-01-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and conformational analysis of a locked analogue of carbovir built on a bicyclo[3.1.0]hex-2-enyl template. AN - 71517811; 14714758 AB - The synthesis and biological evaluation of a carbovir analogue (5) built on a bicyclo[3.1.0]hex-2-enyl template is described. A conformational analysis using density functional theory at the B3LYP/6-31G* level has been carried out on the rigid pseudosugar template of 5, the cyclopentene moiety of carbovir and the bicyclo[3.1.0]hex-2-yl pseudosugars of two isomeric carbonucleosides (12 and 13) containing exo- and endo-fused cyclopropane rings. The results show that while the planar configuration of the fused cyclopentane ring of compound 5 helps retain weak anti-HIV activity, the ability of the cyclopentene ring of carbovir to easily adopt a planar or puckered conformation with little energy penalty may prove to be a crucial advantage. The bicyclo[3.1.0]hex-2-yl nucleosides 12 and 13 that were inactive against HIV exhibited stiffer resistance to having a planar, fused cyclopentane moiety. JF - Nucleosides, nucleotides & nucleic acids AU - Choi, Yongseok AU - Sun, Guangyu AU - George, Clifford AU - Nicklaus, Marc C AU - Kelley, James A AU - Marquez, Victor E AD - Laboratory of Medicinal Chemistry, Center for Cancer Research, NCI-Frederick, NIH, Frederick, Maryland 21702, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 2077 EP - 2091 VL - 22 IS - 12 SN - 1525-7770, 1525-7770 KW - Anti-HIV Agents KW - 0 KW - Cyclopentanes KW - Cyclopropanes KW - Dideoxynucleosides KW - carbovir KW - 118353-05-2 KW - Guanosine KW - 12133JR80S KW - cyclopropane KW - 99TB643425 KW - Index Medicus KW - Molecular Structure KW - Stereoisomerism KW - Thermodynamics KW - Humans KW - Cyclopropanes -- chemistry KW - HIV-2 -- drug effects KW - Structure-Activity Relationship KW - Magnetic Resonance Spectroscopy KW - Crystallography, X-Ray KW - Inhibitory Concentration 50 KW - Molecular Conformation KW - T-Lymphocytes -- virology KW - Cyclopentanes -- chemistry KW - HIV-1 -- drug effects KW - Microbial Sensitivity Tests KW - Anti-HIV Agents -- chemistry KW - Anti-HIV Agents -- chemical synthesis KW - Dideoxynucleosides -- chemical synthesis KW - Dideoxynucleosides -- pharmacology KW - Guanosine -- analogs & derivatives KW - Dideoxynucleosides -- chemistry KW - Anti-HIV Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71517811?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleosides%2C+nucleotides+%26+nucleic+acids&rft.atitle=Synthesis+and+conformational+analysis+of+a+locked+analogue+of+carbovir+built+on+a+bicyclo%5B3.1.0%5Dhex-2-enyl+template.&rft.au=Choi%2C+Yongseok%3BSun%2C+Guangyu%3BGeorge%2C+Clifford%3BNicklaus%2C+Marc+C%3BKelley%2C+James+A%3BMarquez%2C+Victor+E&rft.aulast=Choi&rft.aufirst=Yongseok&rft.date=2003-12-01&rft.volume=22&rft.issue=12&rft.spage=2077&rft.isbn=&rft.btitle=&rft.title=Nucleosides%2C+nucleotides+%26+nucleic+acids&rft.issn=15257770&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-17 N1 - Date created - 2004-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of thyroid hormones in human and laboratory animal reproductive health. AN - 71514467; 14745982 AB - The highly conserved nature of the thyroid gland and the thyroid system among mammalian species suggests it is critical to species survival. Studies show the thyroid system plays a critical role in the development of several organ systems, including the reproductive tract. Despite its highly conserved nature, the thyroid system can have widely different effects on reproduction and reproductive tract development in different species. The present review focuses on assessing the role of thyroid hormones in human reproduction and reproductive tract development and comparing it to the role of thyroid hormones in laboratory animal reproduction and reproductive tract development. The review also assesses the effects of thyroid dysfunction on reproductive tract development and function in humans and laboratory animals. Consideration of such information is important in designing, conducting, and interpreting studies to assess the potential effects of thyroid toxicants on reproduction and development. JF - Birth defects research. Part B, Developmental and reproductive toxicology AU - Choksi, Neepa Y AU - Jahnke, Gloria D AU - St Hilaire, Cathy AU - Shelby, Michael AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 479 EP - 491 VL - 68 IS - 6 SN - 1542-9733, 1542-9733 KW - Thyroid Hormones KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Models, Chemical KW - Placenta -- metabolism KW - Models, Biological KW - Male KW - Female KW - Urogenital System -- drug effects KW - Thyroid Gland -- physiology KW - Urogenital System -- embryology KW - Thyroid Hormones -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71514467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Birth+defects+research.+Part+B%2C+Developmental+and+reproductive+toxicology&rft.atitle=Role+of+thyroid+hormones+in+human+and+laboratory+animal+reproductive+health.&rft.au=Choksi%2C+Neepa+Y%3BJahnke%2C+Gloria+D%3BSt+Hilaire%2C+Cathy%3BShelby%2C+Michael&rft.aulast=Choksi&rft.aufirst=Neepa&rft.date=2003-12-01&rft.volume=68&rft.issue=6&rft.spage=479&rft.isbn=&rft.btitle=&rft.title=Birth+defects+research.+Part+B%2C+Developmental+and+reproductive+toxicology&rft.issn=15429733&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-10 N1 - Date created - 2004-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mistletoe and gemcitabine in patients with advanced cancer: a model for the phase I study of botanicals and botanical-drug interactions in cancer therapy. AN - 71513178; 14713326 AB - Plant extracts of the European mistletoe (MTE), Viscum album, the most widely used cancer treatment in Germany, have been used in European countries as sole intervention or as adjunct to conventional cancer therapies for more than 80 years. Preclinical data suggest immunostimulatory and cytotoxic effects of MTE. While the clinical efficacy of MTE in cancer is being investigated, toxicity and potential interactions of MTE with standard chemotherapeutic agents are unknown. Gemcitabine is an approved antimetabolite chemotherapeutic agent effective as single agent in patients with solid tumors (ST). The documented metabolism and pharmacokinetics of gemcitabine make this agent well suited for the study of botanical-chemotherapy drug interactions (BDIA) in cancer. Based on reports of altered drug metabolism associated with botanical preparations, research into BDIA has intensified. The phase I, 2-stage, dose-escalation study outlined here will test MTE with gemcitabine as a paradigm for the phase I investigation of botanical-drug combination treatments in patients with advanced ST. The protocol including the following components has been reviewed and approved by the National Cancer Institute Institutional Review Board (IRB), the National Naval Medical Center IRB, and the Navy Clinical Investigation Program (study 02-074): (1) use of a standardized MTE, approved by the Food and Drug Administration for investigational use; (2) independent verification of key MTE components considered biologically active; (3) identification of contaminants and adulterants; (4) pharmacokinetics of gemcitabine and its principal metabolites before and upon exposure to MTE; (5) safety and toxicity data collection; (6) assays of plasma ML antibody production in vivo; and (7) pharmacodynamic studies of the botanical-drug combination. JF - Integrative cancer therapies AU - Mansky, Patrick J AU - Grem, Jean AU - Wallerstedt, Dawn B AU - Monahan, Brian P AU - Blackman, Marc R AD - National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 20892-2669, USA. manskyp@mail.nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 345 EP - 352 VL - 2 IS - 4 SN - 1534-7354, 1534-7354 KW - Plant Extracts KW - 0 KW - Plant Proteins KW - viscum album peptide KW - Deoxycytidine KW - 0W860991D6 KW - gemcitabine KW - B76N6SBZ8R KW - Index Medicus KW - Drug Interactions KW - Humans KW - Complementary Therapies -- standards KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Research Design KW - Models, Theoretical KW - Phytotherapy KW - Neoplasms -- drug therapy KW - Plant Proteins -- therapeutic use KW - Deoxycytidine -- adverse effects KW - Viscum album KW - Plant Proteins -- adverse effects KW - Deoxycytidine -- analogs & derivatives KW - Clinical Trials, Phase I as Topic KW - Plant Extracts -- therapeutic use KW - Deoxycytidine -- therapeutic use KW - Plant Extracts -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71513178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Cell&rft.atitle=Protein+microarrays%3A+Meeting+analytical+challenges+for+clinical+applications&rft.au=Liotta%2C+LA%3BEspina%2C+V%3BMehta%2C+AI%3BCalvert%2C+V%3BRosenblatt%2C+K%3BGeho%2C+D%3BMunson%2C+P+J%3BYoung%2C+L%3BWulfkuhle%2C+J%3BPetricoin+III%2C+EF&rft.aulast=Liotta&rft.aufirst=LA&rft.date=2003-04-01&rft.volume=3&rft.issue=4&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Cancer+Cell&rft.issn=15356108&rft_id=info:doi/10.1016%2FS1535-6108%2803%2900086-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-26 N1 - Date created - 2004-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical trial of endorectal amifostine for radioprotection in patients with prostate cancer: rationale and early results. AN - 71511896; 14727242 AB - Tolerance of the normal rectal mucosa to radiation injury limits the dose that can be safely delivered to the prostate gland with definitive external beam radiation therapy. The radioprotective agent amifostine (Ethyol; MedImmune, Inc, Gaithersburg, MD) is approved for intravenous use. Laboratory studies indicate that rectal administration results in preferential accumulation of amifostine in the rectal mucosa, and in clinical studies, neither free parent compound nor free active metabolite has been detected in the systemic circulation. This trial evaluates the rates of early and late rectal toxicities in patients with prostate cancer receiving definitive or adjuvant three-dimensional conformal external beam radiation therapy and concurrent daily endorectal applications of amifostine. Endpoints include Radiation Therapy Oncology Group acute and late toxicity gradings, Expanded Prostate Cancer Index Composite self-assessment questionnaires, and proctoscopic examinations with scoring of mucosal damage measured before, during, and after treatment. Eleven patients have been enrolled to date; 10 have completed radiotherapy and three have been followed-up to 6 months. Two patients received 66 Gy to the prostatic bed post-prostatectomy; five patients received 74 Gy and three received 76 Gy to the prostate gland. In all patients, daily fractionation was 2 Gy, and 1 g of amifostine (50 mg/mL in 20 mL reconstituted saline) was administered endorectally 40 minutes before radiation delivery. Daily endorectal administration was well tolerated. To date, six patients have experienced grade 2 (Radiation Therapy Oncology Group) acute toxicities, all but one because of frequent bowel movements relieved by loperamide. The initial trial will proceed until 18 patients are accrued, at which time an interval evaluation of both early and late toxicity endpoints will be conducted. JF - Seminars in oncology AU - Ménard, Cynthia AU - Camphausen, Kevin AU - Muanza, Thierry AU - Sears-Crouse, Nancy AU - Smith, Sharon AU - Ben-Josef, Edgar AU - Coleman, C Norman AD - Radiation Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institute of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 63 EP - 67 VL - 30 IS - 6 Suppl 18 SN - 0093-7754, 0093-7754 KW - Radiation-Protective Agents KW - 0 KW - Amifostine KW - M487QF2F4V KW - Index Medicus KW - Radiotherapy, Conformal KW - Radiotherapy Dosage KW - Radiation Injuries -- prevention & control KW - Humans KW - Aged KW - Middle Aged KW - Administration, Rectal KW - Male KW - Amifostine -- therapeutic use KW - Radiation-Protective Agents -- therapeutic use KW - Radiation-Protective Agents -- administration & dosage KW - Amifostine -- administration & dosage KW - Prostatic Neoplasms -- radiotherapy KW - Adenocarcinoma -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71511896?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Clinical+trial+of+endorectal+amifostine+for+radioprotection+in+patients+with+prostate+cancer%3A+rationale+and+early+results.&rft.au=M%C3%A9nard%2C+Cynthia%3BCamphausen%2C+Kevin%3BMuanza%2C+Thierry%3BSears-Crouse%2C+Nancy%3BSmith%2C+Sharon%3BBen-Josef%2C+Edgar%3BColeman%2C+C+Norman&rft.aulast=M%C3%A9nard&rft.aufirst=Cynthia&rft.date=2003-12-01&rft.volume=30&rft.issue=6+Suppl+18&rft.spage=63&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 - 2004-02-17 N1 - Date created - 2004-01-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide does not mediate but inhibits transformation and tumor phenotype. AN - 71502632; 14707269 AB - Although inducible nitric oxide synthase (iNOS) and nitric oxide (NO) are implicated in tumor pathology, their role in the early stages of carcinogenesis is not well defined. Tumor necrosis factor alpha (TNFalpha) induces iNOS and NO production in transformation-sensitive JB6 P+, but not in transformation-resistant JB6 P-, mouse epidermal cells. We tested the hypothesis that iNOS, by generating NO and reactive nitrogen species, mediates tumor promoter-induced transformation. Specific [N-[3-(aminomethyl)benzyl]acetamidine (1400W)] and non-specific (N(omega)-methyl-L-arginine) iNOS inhibitors significantly reduced TNFalpha-induced NO production in P+ cells but both iNOS inhibitors enhanced TNFalpha-induced anchorage-independent transformation, thus ruling out a mediator role and suggesting an inhibitor role for NO. Independent support for an inhibitor role came from the observation that the NO donor [(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO)] inhibited TNFalpha- and 12-O-tetradecanoylphorbol-13-acetate-induced transformation. DETA/NO treatment also suppressed tumor phenotype in tumorigenic JB6 RT101 (Tx) cells. Higher concentrations of DETA/NO induced apoptosis. The transformation inhibitory effect of lower DETA/NO concentrations may be attributable in part to inhibition by NO of NF-kappaB-dependent but not of AP-1-dependent transcription. (a) induction of iNOS and NO production does not mediate but actually prevents tumor promotion; (b) iNOS inhibitors enhance the transformation response, and therefore appear not to be appropriate as chemoprevention agents; and (c) NO has both chemopreventive and tumoricidal effects, suggesting promise in cancer chemoprevention and therapy. JF - Molecular cancer therapeutics AU - Dhar, Arindam AU - Brindley, June M AU - Stark, Cristi AU - Citro, Michael L AU - Keefer, Larry K AU - Colburn, Nancy H AD - Gene Regulation Section, Basic Research Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA. adhar@ncifcrf.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 1285 EP - 1293 VL - 2 IS - 12 SN - 1535-7163, 1535-7163 KW - DNA Primers KW - 0 KW - NF-kappa B KW - Nitric Oxide Donors KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Apoptosis -- physiology KW - Mice KW - NF-kappa B -- physiology KW - Nitric Oxide Donors -- pharmacology KW - Phenotype KW - Base Sequence KW - Transcriptional Activation -- physiology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Tumor Necrosis Factor-alpha -- antagonists & inhibitors KW - Nitric Oxide Synthase -- metabolism KW - Cell Line KW - Nitric Oxide -- physiology KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71502632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cancer+therapeutics&rft.atitle=Nitric+oxide+does+not+mediate+but+inhibits+transformation+and+tumor+phenotype.&rft.au=Dhar%2C+Arindam%3BBrindley%2C+June+M%3BStark%2C+Cristi%3BCitro%2C+Michael+L%3BKeefer%2C+Larry+K%3BColburn%2C+Nancy+H&rft.aulast=Dhar&rft.aufirst=Arindam&rft.date=2003-12-01&rft.volume=2&rft.issue=12&rft.spage=1285&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+therapeutics&rft.issn=15357163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of CYP1A1 in tumor cells by the antitumor agent 2-[4-amino-3-methylphenyl]-5-fluoro-benzothiazole: a potential surrogate marker for patient sensitivity. AN - 71497341; 14707267 AB - A candidate antitumor agent, 2-(4-amino-3-methylphenyl)-5-fluoro-benzothiazole (5F-203), like its non-fluorinated parent compound (DF-203), has a unique cytotoxicity pattern in the National Cancer Institute in vitro anticancer drug screen. These compounds show selective toxicity for a subset of cell types including estrogen receptor positive breast cancer and certain renal and ovarian cancer cell lines. Metabolic activation of these benzothiazoles seems to be mediated through the CYP1 family of cytochrome P450s. In an effort to characterize the involvement of CYP1A1 and CYP1B1 in the unique toxicity response of 5F-203, constitutive and 5F-203-induced gene expression patterns were measured in 60 cell lines of the National Cancer Institute drug screen using TaqMan real-time PCR. The patterns of CYP1A1 and CYP1B1 gene expression in the 60 cell lines were correlated with the toxicity pattern of 5F-203 and DF-203. There was significant correlation between drug sensitivity and induced CYP1A1 (R = 0.752, P < 0.001), but not constitutive CYP1A1 mRNA expression. CYP1A1 protein expression was found to mirror the corresponding gene expression, indicating that gene expression changes were concordant with function. Treatment of sensitive cell lines with 10 micro M resveratrol, an inhibitor of CYP1A1 induction, in combination with either 1 or 10 micro M 5F-203 showed an ablation of the observed CYP1A1, but not CYP1B1 mRNA induction in parallel with a decreased sensitivity to 5F-203. Fine needle aspirates were obtained from a variety of human tumor xenografts, and treated ex vivo with 1 micro M 5F-203 for 24 h. In these samples, induction of CYP1A1 by 5F-203 correlated with in vitro sensitivity (R = 0.711, P < 0.05), and corresponded to in vivo sensitivity in human tumor xenografts. These data are concordant with the idea that toxicity of 5F-203 requires activation by CYP1A1, and therefore induction of CYP1A1 mRNA in response to 5F-203 treatments ex vivo may provide a possible surrogate marker for determination of drug-sensitive tumors in patients. JF - Molecular cancer therapeutics AU - Hose, Curtis D AU - Hollingshead, Melinda AU - Sausville, Edward A AU - Monks, Anne AD - SAIC-Frederick, National Cancer Institute-Frederick, Developmental Therapeutics Program, STB-Functional Genomics Laboratory, Frederick, MD 21702, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 1265 EP - 1272 VL - 2 IS - 12 SN - 1535-7163, 1535-7163 KW - 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole KW - 0 KW - Antineoplastic Agents KW - DNA Primers KW - RNA, Messenger KW - Thiazoles KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Humans KW - Enzyme Induction KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Thiazoles -- pharmacology KW - Cytochrome P-450 CYP1A1 -- genetics KW - Antineoplastic Agents -- pharmacology KW - Cytochrome P-450 CYP1A1 -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71497341?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cancer+therapeutics&rft.atitle=Induction+of+CYP1A1+in+tumor+cells+by+the+antitumor+agent+2-%5B4-amino-3-methylphenyl%5D-5-fluoro-benzothiazole%3A+a+potential+surrogate+marker+for+patient+sensitivity.&rft.au=Hose%2C+Curtis+D%3BHollingshead%2C+Melinda%3BSausville%2C+Edward+A%3BMonks%2C+Anne&rft.aulast=Hose&rft.aufirst=Curtis&rft.date=2003-12-01&rft.volume=2&rft.issue=12&rft.spage=1265&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+therapeutics&rft.issn=15357163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endocrine disruptors and the obesity epidemic. AN - 71482383; 14677558 JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Heindel, Jerrold J AD - Cellular, Organs, and Systems Pathobiology Branch, Division of Extramural Research and Training, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. heindel_j@niehs.nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 247 EP - 249 VL - 76 IS - 2 SN - 1096-6080, 1096-6080 KW - Environmental Pollutants KW - 0 KW - Hormone Antagonists KW - Index Medicus KW - Humans KW - United States -- epidemiology KW - Obesity -- etiology KW - Obesity -- epidemiology KW - Environmental Exposure -- adverse effects KW - Disease Outbreaks KW - Environmental Pollutants -- adverse effects KW - Hormone Antagonists -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71482383?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Endocrine+disruptors+and+the+obesity+epidemic.&rft.au=Heindel%2C+Jerrold+J&rft.aulast=Heindel&rft.aufirst=Jerrold&rft.date=2003-12-01&rft.volume=76&rft.issue=2&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-06 N1 - Date created - 2003-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacogenetics of estrogen metabolism and transport in relation to cancer. AN - 71477268; 14683478 AB - Exposure to estrogens has been long associated with the genesis of human malignancies, including breast, ovarian, and endometrial cancer. A variety of phase I and II enzymes are involved in the metabolic activation and de-activation of estrogens, including cytochrome p450 isoforms, estrone sulfatase, sulfotransferases, catechol-o-methyltransferase, and uridine-5'-diphosphate glucuronosyltransferase. In addition, at least one ATP-binding cassette gene (i.e., ABCG2) is involved in estrogen transport. Variability in the expression levels of these proteins may have important consequences for an individual-s susceptibility to certain malignancies. Naturally occurring variants in the genes involved in estrogen exposure levels have been identified that might affect protein function and expression. This review focuses on recent advances in the pharmacogenetics of these proteins, and discusses potential clinical ramifications of these genetic variants. JF - Current drug metabolism AU - Lakhani, Nehal J AU - Venitz, Jürgen AU - Figg, William D AU - Sparreboom, Alex AD - Clinical Pharmacology Research Core, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 505 EP - 513 VL - 4 IS - 6 SN - 1389-2002, 1389-2002 KW - Antineoplastic Agents KW - 0 KW - Estrogens KW - Estradiol KW - 4TI98Z838E KW - 2-methoxyestradiol KW - 6I2QW73SR5 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals KW - Diethylstilbestrol -- therapeutic use KW - Humans KW - Diethylstilbestrol -- pharmacology KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology KW - Male KW - Female KW - Estradiol -- analogs & derivatives KW - Neoplasms -- drug therapy KW - Estrogens -- metabolism KW - Estradiol -- pharmacology KW - Estradiol -- therapeutic use KW - Genetic Predisposition to Disease KW - Estrogens -- biosynthesis KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71477268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+drug+metabolism&rft.atitle=Pharmacogenetics+of+estrogen+metabolism+and+transport+in+relation+to+cancer.&rft.au=Lakhani%2C+Nehal+J%3BVenitz%2C+J%C3%BCrgen%3BFigg%2C+William+D%3BSparreboom%2C+Alex&rft.aulast=Lakhani&rft.aufirst=Nehal&rft.date=2003-12-01&rft.volume=4&rft.issue=6&rft.spage=505&rft.isbn=&rft.btitle=&rft.title=Current+drug+metabolism&rft.issn=13892002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-30 N1 - Date created - 2003-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of efficacy of fadrozole in treating precocious puberty in girls with the McCune-Albright syndrome. AN - 71466559; 14671160 AB - We administered the aromatase inhibitor fadrozole to 16 girls with gonadotropin-independent precocious puberty due to the McCune-Albright syndrome. The girls' ages ranged from 3.2-9.7 yr, and their bone ages ranged from 5.75-14.25 yr. After baseline evaluations, fadrozole was started at a dose of 240 microg/kg.d (equivalent to the dose recommended for therapy of estrogen-dependent breast cancer) for 12-21 months and increased to 480 microg/kg.d for an additional 12 months in 10 girls. During treatment, seven girls had evidence of central precocious puberty; hence, the GnRH agonist deslorelin (4 microg/kg.d sc) was added to their regimen. One girl was on a long-acting GnRH agonist from the start of treatment. Patients were evaluated at 2-6-month intervals throughout treatment. After the first 6-12 months of treatment, fadrozole showed some benefits in 10 girls, including decrease in frequency of menses and/or rates of linear growth and bone maturation; however, fadrozole had no significant benefit in the group as a whole. The seven girls with evidence of central precocious puberty had no slowing in the progression of their puberty during the combined fadrozole and GnRH analog treatment. Adverse effects of fadrozole included inhibition of cortisol and aldosterone biosynthesis at the dose of 480 microg/kg.d, without clinical evidence of adrenal insufficiency. In addition, three patients complained of nonspecific abdominal pain during fadrozole treatment. In one patient, this resolved with a reduction in dose from 480 to 240 microg/kg.d; in two patients, it resolved spontaneously. One girl had muscle weakness and constipation on the 480 microg/kg.d. This resolved after discontinuation of the drug. We conclude that fadrozole is not sufficiently potent to block estrogen synthesis in most girls with gonadotropin-independent precocious puberty due to the McCune-Albright syndrome and may impair the adrenocortical stress response. JF - The Journal of clinical endocrinology and metabolism AU - Nunez, Susan B AU - Calis, Karim AU - Cutler, Gordon B AU - Jones, Janet AU - Feuillan, Penelope P AD - Developmental Endocrinology Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 5730 EP - 5733 VL - 88 IS - 12 SN - 0021-972X, 0021-972X KW - Aromatase Inhibitors KW - 0 KW - Enzyme Inhibitors KW - Estrone KW - 2DI9HA706A KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Estradiol KW - 4TI98Z838E KW - Triptorelin Pamoate KW - 57773-63-4 KW - Fadrozole KW - H3988M64PU KW - deslorelin KW - TKG3I66TVE KW - Abridged Index Medicus KW - Index Medicus KW - Gonadotropin-Releasing Hormone -- agonists KW - Treatment Failure KW - Humans KW - Ovary -- diagnostic imaging KW - Aging KW - Child KW - Ultrasonography KW - Child, Preschool KW - Drug Therapy, Combination KW - Age Determination by Skeleton KW - Growth KW - Estradiol -- blood KW - Menstruation KW - Estrone -- blood KW - Female KW - Enzyme Inhibitors -- adverse effects KW - Fadrozole -- adverse effects KW - Enzyme Inhibitors -- therapeutic use KW - Puberty, Precocious -- diagnostic imaging KW - Fibrous Dysplasia, Polyostotic -- complications KW - Fadrozole -- therapeutic use KW - Puberty, Precocious -- drug therapy KW - Puberty, Precocious -- etiology KW - Triptorelin Pamoate -- therapeutic use KW - Triptorelin Pamoate -- analogs & derivatives KW - Puberty, Precocious -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71466559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Lack+of+efficacy+of+fadrozole+in+treating+precocious+puberty+in+girls+with+the+McCune-Albright+syndrome.&rft.au=Nunez%2C+Susan+B%3BCalis%2C+Karim%3BCutler%2C+Gordon+B%3BJones%2C+Janet%3BFeuillan%2C+Penelope+P&rft.aulast=Nunez&rft.aufirst=Susan&rft.date=2003-12-01&rft.volume=88&rft.issue=12&rft.spage=5730&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-15 N1 - Date created - 2003-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The adaptive imbalance in base excision-repair enzymes generates microsatellite instability in chronic inflammation. AN - 71459417; 14679184 AB - Chronic infection and associated inflammation are key contributors to human carcinogenesis. Ulcerative colitis (UC) is an oxyradical overload disease and is characterized by free radical stress and colon cancer proneness. Here we examined tissues from noncancerous colons of ulcerative colitis patients to determine (a) the activity of two base excision-repair enzymes, AAG, the major 3-methyladenine DNA glycosylase, and APE1, the major apurinic site endonuclease; and (b) the prevalence of microsatellite instability (MSI). AAG and APE1 were significantly increased in UC colon epithelium undergoing elevated inflammation and MSI was positively correlated with their imbalanced enzymatic activities. These latter results were supported by mechanistic studies using yeast and human cell models in which overexpression of AAG and/or APE1 was associated with frameshift mutations and MSI. Our results are consistent with the hypothesis that the adaptive and imbalanced increase in AAG and APE1 is a novel mechanism contributing to MSI in patients with UC and may extend to chronic inflammatory or other diseases with MSI of unknown etiology. JF - The Journal of clinical investigation AU - Hofseth, Lorne J AU - Khan, Mohammed A AU - Ambrose, Mark AU - Nikolayeva, Olga AU - Xu-Welliver, Meng AU - Kartalou, Maria AU - Hussain, S Perwez AU - Roth, Richard B AU - Zhou, Xiaoling AU - Mechanic, Leah E AU - Zurer, Irit AU - Rotter, Varda AU - Samson, Leona D AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 1887 EP - 1894 VL - 112 IS - 12 SN - 0021-9738, 0021-9738 KW - Antigens, CD KW - 0 KW - Antigens, Differentiation, Myelomonocytic KW - CD68 antigen, human KW - 3-methyladenine-DNA glycosylase KW - EC 3.2.2.- KW - DNA Glycosylases KW - APEX1 protein, human KW - EC 4.2.99.18 KW - DNA-(Apurinic or Apyrimidinic Site) Lyase KW - Abridged Index Medicus KW - Index Medicus KW - Frameshift Mutation KW - Antigens, CD -- biosynthesis KW - Dose-Response Relationship, Drug KW - Colorectal Neoplasms -- metabolism KW - Humans KW - Colon -- metabolism KW - Colitis, Ulcerative -- metabolism KW - Antigens, Differentiation, Myelomonocytic -- biosynthesis KW - K562 Cells KW - Time Factors KW - Immunohistochemistry KW - Densitometry KW - Microsatellite Repeats KW - DNA-(Apurinic or Apyrimidinic Site) Lyase -- genetics KW - DNA Repair KW - Base Pair Mismatch KW - DNA Glycosylases -- genetics KW - Inflammation -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71459417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=The+adaptive+imbalance+in+base+excision-repair+enzymes+generates+microsatellite+instability+in+chronic+inflammation.&rft.au=Hofseth%2C+Lorne+J%3BKhan%2C+Mohammed+A%3BAmbrose%2C+Mark%3BNikolayeva%2C+Olga%3BXu-Welliver%2C+Meng%3BKartalou%2C+Maria%3BHussain%2C+S+Perwez%3BRoth%2C+Richard+B%3BZhou%2C+Xiaoling%3BMechanic%2C+Leah+E%3BZurer%2C+Irit%3BRotter%2C+Varda%3BSamson%2C+Leona+D%3BHarris%2C+Curtis+C&rft.aulast=Hofseth&rft.aufirst=Lorne&rft.date=2003-12-01&rft.volume=112&rft.issue=12&rft.spage=1887&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-21 N1 - Date created - 2003-12-17 N1 - Date revised - 2017-01-13 N1 - 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Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-specific cancer incidence and mortality after cerebral angiography with radioactive thorotrast. AN - 71458657; 14640794 AB - Few opportunities exist to evaluate the carcinogenic effects of long-term internal exposure to alpha-particle-emitting radionuclides. Patients injected with Thorotrast (thorium-232) during radiographic procedures, beginning in the 1930s, provide one such valuable opportunity. We evaluated site-specific cancer incidence and mortality among an international cohort of 3,042 patients injected during cerebral angiography with either Thorotrast (n = 1,650) or a nonradioactive agent (n = 1,392) and who survived 2 or more years. Standardized incidence ratios (SIR) for Thorotrast and comparison patients (Denmark and Sweden) were estimated and relative risks (RR), adjusted for population, age and sex, were generated with multivariate statistical modeling. For U.S. patients, comparable procedures were used to estimate standardized mortality ratios (SMR) and RR, representing the first evaluation of long-term, site-specific cancer mortality in this group. Compared with nonexposed patients, significantly increased risks in Thorotrast patients were observed for all incident cancers combined (RR = 3.4, 95% CI 2.9-4.1, n = 480, Denmark and Sweden) and for cancer mortality (RR = 4.0, 95% CI 2.5-6.7, n = 114, U.S.). Approximately 335 incident cancers were above expectation, with large excesses seen for cancers of the liver, bile ducts and gallbladder (55% or 185 excess cancers) and leukemias other than CLL (8% or 26 excess cancers). The RR of all incident cancers increased with time since angiography (P 20 ml Thorotrast, the cumulative excess risk of cancer incidence remained elevated for up to 50 years and approached 97%. Caution is needed in interpreting the excess risks observed for site-specific cancers, however, because of the potential bias associated with the selection of cohort participants, noncomparability with respect to the internal or external comparison groups, and confounding by indication. Nonetheless, the substantial risks associated with liver cancer and leukemia indicate that unique and prolonged exposure to alpha-particle-emitting Thorotrast increased carcinogenic risks. JF - Radiation research AU - Travis, Lois B AU - Hauptmann, Michael AU - Gaul, Linda Knudson AU - Storm, Hans H AU - Goldman, Marlene B AU - Nyberg, Ullakarin AU - Berger, Eric AU - Janower, Murray L AU - Hall, Per AU - Monson, Richard R AU - Holm, Lars-Erik AU - Land, Charles E AU - Schottenfeld, David AU - Boice, John D AU - Andersson, Michael AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland 20892, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 691 EP - 706 VL - 160 IS - 6 SN - 0033-7587, 0033-7587 KW - Thorium Dioxide KW - 9XA7X17UQC KW - Index Medicus KW - Space life sciences KW - Lung Neoplasms -- epidemiology KW - Gastrointestinal Neoplasms -- epidemiology KW - Humans KW - Adult KW - Incidence KW - Aged KW - Middle Aged KW - Liver Neoplasms -- epidemiology KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Male KW - Female KW - Thorium Dioxide -- adverse effects KW - Neoplasms -- mortality KW - Neoplasms, Radiation-Induced -- epidemiology KW - Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- mortality KW - Cerebral Angiography -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71458657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Site-specific+cancer+incidence+and+mortality+after+cerebral+angiography+with+radioactive+thorotrast.&rft.au=Travis%2C+Lois+B%3BHauptmann%2C+Michael%3BGaul%2C+Linda+Knudson%3BStorm%2C+Hans+H%3BGoldman%2C+Marlene+B%3BNyberg%2C+Ullakarin%3BBerger%2C+Eric%3BJanower%2C+Murray+L%3BHall%2C+Per%3BMonson%2C+Richard+R%3BHolm%2C+Lars-Erik%3BLand%2C+Charles+E%3BSchottenfeld%2C+David%3BBoice%2C+John+D%3BAndersson%2C+Michael&rft.aulast=Travis&rft.aufirst=Lois&rft.date=2003-12-01&rft.volume=160&rft.issue=6&rft.spage=691&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 - 2004-01-06 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduction in Smad2/3 signaling enhances tumorigenesis but suppresses metastasis of breast cancer cell lines. AN - 71458139; 14678987 AB - The role of transforming growth factor beta in breast cancer is controversial with tumor suppressor and pro-oncogenic activities having been demonstrated. To address whether the same or different signal transduction pathways mediate these opposing activities, we manipulated the Smad2/3 signaling pathway in cells of common origin but differing degrees of malignancy derived from MCF10A human breast cells. We show that interference with endogenous Smad2/3 signaling enhances the malignancy of xenografted tumors of premalignant and well-differentiated tumor cells but strongly suppresses lung metastases of more aggressive carcinoma cells after tail vein injection. Overexpression of Smad3 in the same cells has opposite effects. The data demonstrate that the Smad2/3 signaling pathway mediates tumor suppressor and prometastatic signals, depending on the cellular context. JF - Cancer research AU - Tian, Fang AU - DaCosta Byfield, Stacey AU - Parks, W Tony AU - Yoo, Stephen AU - Felici, Angelina AU - Tang, Binwu AU - Piek, Ester AU - Wakefield, Lalage M AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 2003/12/01/ PY - 2003 DA - 2003 Dec 01 SP - 8284 EP - 8292 VL - 63 IS - 23 SN - 0008-5472, 0008-5472 KW - DNA-Binding Proteins KW - 0 KW - SMAD2 protein, human KW - SMAD3 protein, human KW - Smad2 Protein KW - Smad2 protein, mouse KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Humans KW - Cell Division -- physiology KW - Cell Line, Tumor KW - Mice KW - Mice, Inbred BALB C KW - Neoplasm Transplantation KW - Transforming Growth Factor beta -- physiology KW - Down-Regulation KW - Phosphorylation KW - Transfection KW - Neoplasm Metastasis KW - Transplantation, Heterologous KW - Female KW - Signal Transduction KW - Breast Neoplasms -- genetics KW - Trans-Activators -- biosynthesis KW - Breast Neoplasms -- pathology KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- biosynthesis KW - Breast Neoplasms -- metabolism KW - DNA-Binding Proteins -- physiology KW - DNA-Binding Proteins -- antagonists & inhibitors KW - Trans-Activators -- physiology KW - Trans-Activators -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71458139?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reduction+in+Smad2%2F3+signaling+enhances+tumorigenesis+but+suppresses+metastasis+of+breast+cancer+cell+lines.&rft.au=Tian%2C+Fang%3BDaCosta+Byfield%2C+Stacey%3BParks%2C+W+Tony%3BYoo%2C+Stephen%3BFelici%2C+Angelina%3BTang%2C+Binwu%3BPiek%2C+Ester%3BWakefield%2C+Lalage+M%3BRoberts%2C+Anita+B&rft.aulast=Tian&rft.aufirst=Fang&rft.date=2003-12-01&rft.volume=63&rft.issue=23&rft.spage=8284&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 - 2004-02-27 N1 - Date created - 2003-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase II trial of carboxyamidotriazole in patients with relapsed epithelial ovarian cancer. AN - 71455280; 14645425 AB - Carboxyamidotriazole (CAI) is a cytostatic inhibitor of nonvoltage-operated calcium channels and calcium channel-mediated signaling pathways. It inhibits angiogenesis, tumor growth, invasion, and metastasis. We hypothesized that CAI would promote disease stabilization lasting >/= 6 months in patients with relapsed ovarian cancer. Patients with epithelial ovarian cancer, good end-organ function, measurable disease, and three or fewer prior regimens were eligible. Oral CAI was given daily using a pharmacokinetic-dosing approach to maintain plasma concentrations between 2 and 4 microg/mL. Radiographic imaging to assess response was performed every 8 weeks. Positive outcome included stabilization or improvement of disease lasting >/= 6 months. Plasma vascular endothelial growth factor (VEGF), interleukin (IL)-8, and matrix metalloproteinase (MMP)-2 were measured. Thirty-six patients were assessable for primary end point analysis, and 38 were assessable for toxicity. Forty-four percent of patients had three prior regimens, more than 50% had four or more disease sites, and 48% had liver metastases. Thirty-three patients reached the targeted concentration range during the first cycle. Eleven patients (31%) attained the >/= 6-month outcome end point, with one partial response (8 months) and three minor responses (8, 12+, and 13 months). Median time to progression was 3.6 months (range, 1.6 to 13.3 months). CAI was well tolerated, with mostly grade 1 to 2 toxicity. Grade 3 events included fatigue (5%), vomiting (2%), neutropenic fever (2%), and neutropenia (2%). There were no grade 4 adverse events. No associations between VEGF, IL-8, and MMP-2 with CAI concentration or clinical outcome were observed. CAI is a potential agent for additional study in the stabilization of relapsed ovarian cancer. Given a limited toxicity profile, it may have utility as a maintenance therapeutic agent for this disease. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Hussain, Mahrukh M AU - Kotz, Herbert AU - Minasian, Lori AU - Premkumar, Ahalya AU - Sarosy, Gisele AU - Reed, Eddie AU - Zhai, Suoping AU - Steinberg, Seth M AU - Raggio, Miranda AU - Oliver, Vyta Kulpa AU - Figg, William D AU - Kohn, Elise C AD - Medical Oncology Clinical Research Unit, Medical Ovarian Cancer Clinic and Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1500, USA. Y1 - 2003/12/01/ PY - 2003 DA - 2003 Dec 01 SP - 4356 EP - 4363 VL - 21 IS - 23 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Biomarkers KW - Calcium Channel Blockers KW - Triazoles KW - carboxyamido-triazole KW - 99519-84-3 KW - Index Medicus KW - Administration, Oral KW - Humans KW - Salvage Therapy KW - Aged KW - Carcinoma, Papillary -- metabolism KW - Cystadenocarcinoma, Serous -- metabolism KW - Carcinoma, Endometrioid -- metabolism KW - Cystadenocarcinoma, Serous -- drug therapy KW - Survival Rate KW - Aged, 80 and over KW - Biomarkers -- analysis KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Carcinoma, Endometrioid -- drug therapy KW - Carcinoma, Papillary -- drug therapy KW - Female KW - Ovarian Neoplasms -- metabolism KW - Neoplasms, Glandular and Epithelial -- metabolism KW - Antineoplastic Agents -- pharmacokinetics KW - Triazoles -- adverse effects KW - Triazoles -- pharmacokinetics KW - Calcium Channel Blockers -- pharmacokinetics KW - Ovarian Neoplasms -- drug therapy KW - Antineoplastic Agents -- adverse effects KW - Neoplasm Recurrence, Local -- metabolism KW - Neoplasms, Glandular and Epithelial -- drug therapy KW - Neoplasm Recurrence, Local -- drug therapy KW - Calcium Channel Blockers -- adverse effects KW - Triazoles -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Calcium Channel Blockers -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71455280?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+II+trial+of+carboxyamidotriazole+in+patients+with+relapsed+epithelial+ovarian+cancer.&rft.au=Hussain%2C+Mahrukh+M%3BKotz%2C+Herbert%3BMinasian%2C+Lori%3BPremkumar%2C+Ahalya%3BSarosy%2C+Gisele%3BReed%2C+Eddie%3BZhai%2C+Suoping%3BSteinberg%2C+Seth+M%3BRaggio%2C+Miranda%3BOliver%2C+Vyta+Kulpa%3BFigg%2C+William+D%3BKohn%2C+Elise+C&rft.aulast=Hussain&rft.aufirst=Mahrukh&rft.date=2003-12-01&rft.volume=21&rft.issue=23&rft.spage=4356&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 - 2004-01-05 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of aldose reductase inhibitors and galactose withdrawal on fluorescein angiographic lesions in galactose-fed dogs. AN - 71447411; 14662595 AB - To assess the effect of aldose reductase inhibitor (ARI) M79175 (2-methyl-6-fluoro-spiro-chroman-4-5'-imidazolidine-2',4'-dione) administration and galactose withdrawal on the progression of retinal changes using fluorescein angiography in galactose-fed dogs. Thirty male beagles were randomized into 4 groups. Three dogs were fed a normal control diet containing 30% nonnutritive fiber for 74 months (control group), 11 dogs a 30% galactose diet for 74 months (continuous galactose group), 8 dogs a 30% galactose diet for 36 months followed by replacement with a normal diet for 36 months (galactose withdrawal group), and 8 dogs a 30% galactose diet supplemented with M79175 for 34 months followed by replacement with a normal diet and removal of M79175 treatment for 38 months (ARI-treated galactose withdrawal group). Stereoscopic color fundus photography and fluorescein angiography, performed at baseline and follow-up, were assessed for the clinical development of retinopathy, including the first appearance of hyperfluorescence, varying severity of retinal nonperfusion, and retinal neovascularization. Histopathologic features were examined in selected dogs. All dogs in the 3 groups fed the 30% galactose diet developed areas of hyperfluorescence and nonperfusion. Of these dogs, only those supplemented with the ARI did not develop areas of nonperfusion greater than or equal to half the field and retinal neovascularization. Parametric survival analysis showed significant differences (galactose withdrawal group vs ARI-treated galactose withdrawal group) in the median times to the development of nonperfusion greater than or equal to half the field (P =.003) and retinal neovascularization (P =.03). Normalization of glycemic control with galactose withdrawal and ARI treatment may delay the onset and progression of retinal lesions in galactose-fed dogs. Clinical Relevance Perfect glycemic control after a period of poor control does not completely prevent the progression of retinal lesions. Therapy with ARIs may potentially be important in the prevention of retinal lesions associated with diabetic eye disease. JF - Archives of ophthalmology (Chicago, Ill. : 1960) AU - Cusick, Michael AU - Chew, Emily Y AU - Ferris, Frederick AU - Cox, Terry A AU - Chan, Chi-Chao AU - Kador, Peter F AD - National Eye Institute, National Institutes of Health, and Howard Hughes Medical Institute - National Institutes of Health Research Scholars Program, Bethesda, MD 20892, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 1745 EP - 1751 VL - 121 IS - 12 SN - 0003-9950, 0003-9950 KW - Blood Glucose KW - 0 KW - Enzyme Inhibitors KW - Imidazoles KW - Imidazolidines KW - M 79175 KW - 82319-87-7 KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Galactose KW - X2RN3Q8DNE KW - Abridged Index Medicus KW - Index Medicus KW - Retinal Neovascularization -- prevention & control KW - Retinal Neovascularization -- diagnosis KW - Animals KW - Retinal Neovascularization -- chemically induced KW - Fluorescein Angiography KW - Dogs KW - Disease Progression KW - Retinal Vessels -- drug effects KW - Disease Models, Animal KW - Blood Glucose -- analysis KW - Male KW - Retinal Vessels -- pathology KW - Enzyme Inhibitors -- therapeutic use KW - Diabetic Retinopathy -- diagnosis KW - Diabetic Retinopathy -- chemically induced KW - Galactose -- administration & dosage KW - Imidazoles -- therapeutic use KW - Aldehyde Reductase -- antagonists & inhibitors KW - Diabetic Retinopathy -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71447411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.atitle=Effects+of+aldose+reductase+inhibitors+and+galactose+withdrawal+on+fluorescein+angiographic+lesions+in+galactose-fed+dogs.&rft.au=Cusick%2C+Michael%3BChew%2C+Emily+Y%3BFerris%2C+Frederick%3BCox%2C+Terry+A%3BChan%2C+Chi-Chao%3BKador%2C+Peter+F&rft.aulast=Cusick&rft.aufirst=Michael&rft.date=2003-12-01&rft.volume=121&rft.issue=12&rft.spage=1745&rft.isbn=&rft.btitle=&rft.title=Archives+of+ophthalmology+%28Chicago%2C+Ill.+%3A+1960%29&rft.issn=00039950&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-05 N1 - Date created - 2003-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alpha-1 antitrypsin deficiency is not a rare disease but a disease that is rarely diagnosed. AN - 71436977; 14654440 AB - Articles in the literature on alpha-1 antitrypsin (AAT) deficiency have been interpreted as indicating that AAT deficiency is a rare disease that affects mainly Caucasians (whites) from northern Europe. In a recent publication on the worldwide racial and ethnic distribution of AAT deficiency, new data were presented demonstrating that it is also found in various populations of African blacks; Arabs and Jews in the Middle East; and Central, Far East, and Southeast Asians, as well as whites in Australia, Europe, New Zealand, and North America. The new data on the prevalence of AAT deficiency in other major racial groups worldwide will affect the standards for the diagnosis of AAT deficiency by the medical community, with the realization that is not a rare disease of whites in northern Europe and immigrants from these countries in the New World. In a total population of 4.4 billion in the 58 countries surveyed, there are at least 116 million carriers (those with Pi phenotypes PiMS and PiMZ) and 3.4 million with deficiency allele combinations (phenotypes PiSS, PiSZ, and PiZZ) for the two most prevalent deficiency alleles PiS and PiZ; therefore, the new data suggest that AAT deficiency may be one of the most common serious single-locus genetic diseases in the world. Particularly important is the unique susceptibility of AAT-deficient individuals to exposure to chemical and particulate environmental agents. Such exposures are known to result in both lung and liver disease as well as other adverse health effects. JF - Environmental health perspectives AU - de Serres, Frederick J AD - Laboratory of Molecular Toxicology, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. deserres@bellsouth.net Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 1851 EP - 1854 VL - 111 IS - 16 SN - 0091-6765, 0091-6765 KW - alpha 1-Antitrypsin KW - 0 KW - Index Medicus KW - Phenotype KW - Environmental Exposure -- statistics & numerical data KW - Risk Factors KW - Humans KW - Heterozygote KW - Emphysema -- epidemiology KW - alpha 1-Antitrypsin -- genetics KW - Incidence KW - Smoking -- epidemiology KW - Comorbidity KW - alpha 1-Antitrypsin Deficiency -- therapy KW - alpha 1-Antitrypsin Deficiency -- diagnosis KW - alpha 1-Antitrypsin Deficiency -- genetics KW - alpha 1-Antitrypsin Deficiency -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71436977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alpha-1+antitrypsin+deficiency+is+not+a+rare+disease+but+a+disease+that+is+rarely+diagnosed.&rft.au=de+Serres%2C+Frederick+J&rft.aulast=de+Serres&rft.aufirst=Frederick&rft.date=2003-12-01&rft.volume=111&rft.issue=16&rft.spage=1851&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 - 2004-03-02 N1 - Date created - 2003-12-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Respir Cell Mol Biol. 2002 Jun;26(6):723-30 [12034572] Pediatr Transplant. 2002 Aug;6(4):295-300 [12234269] Respir Med. 2002 Nov;96(11):872-80 [12418584] Chest. 2002 Nov;122(5):1818-29 [12426287] Bull Acad Natl Med. 2002;186(8):1479-86; discussion 1486-7 [12669363] Clin Genet. 2003 Jun;63(6):490-509 [12786756] Environ Health Perspect. 2003 Jun;111(8):1055-64 [12826477] Am J Clin Pathol. 1975 Sep;64(3):304-10 [169686] Adv Hum Genet. 1981;11:1-62, 371-2 [6168185] Am Rev Respir Dis. 1983 Feb;127(2):S43-5 [6600892] Br J Dis Chest. 1983 Jan;77(1):14-27 [6602621] Lancet. 1985 Jan 19;1(8421):152-4 [2857224] Nature. 1985 Jul 4-10;316(6023):79-81 [2989709] Scand J Gastroenterol. 1985 Sep;20(7):835-42 [2996119] Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1468-72 [10556107] Am J Hum Genet. 1987 Nov;41(5):891-906 [2890296] JAMA. 1988 May 20;259(19):2890-5 [3285040] Am J Med. 1988 Jun 24;84(6A):3-12 [3289386] Am Rev Respir Dis. 1988 Aug;138(2):327-36 [3264124] Chest. 1989 Jan;95(1):196-208 [2642408] J Pediatr Gastroenterol Nutr. 1989 Jan;8(1):116-21 [2659760] Crit Rev Clin Lab Sci. 1989;27(6):461-81 [2690855] Nature. 1992 Jun 18;357(6379):605-7 [1608473] Chest. 1993 Mar;103(3):812-5 [8449073] Ann Allergy. 1994 Feb;72(2):105-20; quiz 120-2 [8109800] Am J Hum Genet. 1994 Jul;55(1):126-33 [7912884] Acta Paediatr Suppl. 1994 Feb;393:21-3 [7913350] Thorax. 1994 Jul;49(7):695-8 [8066566] Acta Neurol Scand. 1995 May;91(5):394-8 [7639071] Transplantation. 1997 Feb 15;63(3):480-2 [9039946] J Inherit Metab Dis. 1997 Mar;20(1):9-20 [9061562] Cerebrovasc Dis. 1998 Jan-Feb;8(1):42-4 [9645981] J Pediatr Gastroenterol Nutr. 1998 Jul;27(1):65-74 [9669729] Respir Med. 1998 Mar;92(3):367-77 [9692092] Thorax. 1998 Jun;53(6):501-5 [9713452] Hepatology. 1998 Oct;28(4):1058-63 [9755243] Am J Respir Cell Mol Biol. 1999 Feb;20(2):287-91 [9922220] Eur Respir J. 1999 Feb;13(2):247-51 [10065663] Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):553-8 [10934086] Eur Respir J. 2000 Jul;16(1):50-5 [10933084] Med Klin (Munich). 2002 Mar 15;97(3):137-43 [11957788] N Engl J Med. 2002 Jan 3;346(1):45-53 [11778003] Am J Med Genet. 2001 Dec 15;104(4):287-90 [11754061] Respir Med. 2000 Aug;94 Suppl C:S3-6 [10954247] Hum Genet. 2001 Jan;108(1):20-30 [11214903] Clin Genet. 2001 Jul;60(1):31-41 [11531967] Chest. 1986 Mar;89(3):370-3 [3485034] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The economics of public health: financing drug abuse treatment services. AN - 71432104; 14637010 AB - Drug abuse treatment financing exhibits a heterogeneous set of sources from federal, state, and local governments, as well as private sources from insurance, patient out-of-pocket, and charity. A public health model of drug abuse treatment is presented for a market that can be characterized by excess demand in many communities and an implied policy of rationing. According to best estimates, as many as 6.7 million individuals may need treatment, but only an estimated 1.5 million individuals actually participated in treatment episodes. Since, as demonstrated empirically, drug abuse treatment has a robust and positive social net benefit to society, it is perplexing that treatment financing stops with a rationing outcome that inhibits social welfare. The justification for public financing is centered on the external costs of drug addiction, but subsidization is grounded in the reality that a large number of addicted individuals do not have sufficient resources to pay for treatment out-of-pocket, nor do they have private insurance coverage. Social welfare losses are generated by financial arrangements that are inconsistent with rational budgeting theory and as such would lead to non-optimal organization and management of the drug abuse treatment system. JF - Health policy (Amsterdam, Netherlands) AU - Cartwright, William S AU - Solano, Paul L AD - National Institute of Drug Abuse, NIH, 6001 Executive Boulevard, Room 4222, MSC 9565, Bethesda, MD 20892-9565, USA. wc34b@nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 247 EP - 260 VL - 66 IS - 3 SN - 0168-8510, 0168-8510 KW - Health administration KW - United States KW - Health Services Needs and Demand -- economics KW - Health Services Needs and Demand -- statistics & numerical data KW - Efficiency, Organizational KW - Humans KW - Health Care Rationing -- methods KW - Patient Acceptance of Health Care -- statistics & numerical data KW - Mental Health Services -- utilization KW - Mental Health Services -- economics KW - Health Policy KW - Models, Economic KW - Substance-Related Disorders -- therapy KW - Financing, Government -- methods KW - Budgets -- methods KW - Substance-Related Disorders -- economics KW - Substance Abuse Treatment Centers -- economics KW - Substance Abuse Treatment Centers -- utilization KW - Public Health Administration -- economics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71432104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+policy+%28Amsterdam%2C+Netherlands%29&rft.atitle=The+economics+of+public+health%3A+financing+drug+abuse+treatment+services.&rft.au=Cartwright%2C+William+S%3BSolano%2C+Paul+L&rft.aulast=Cartwright&rft.aufirst=William&rft.date=2003-12-01&rft.volume=66&rft.issue=3&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Health+policy+%28Amsterdam%2C+Netherlands%29&rft.issn=01688510&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-12 N1 - Date created - 2003-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transfusion-associated GVHD after fludarabine therapy in a patient with systemic lupus erythematosus. AN - 71429845; 14641861 AB - Fludarabine, a purine antimetabolite with potent immunosuppressive properties, has previously been associated with the development of transfusion-associated GVHD (TA-GVHD) in patients with hematologic malignancies. Its role as a risk factor for TA-GVHD in patients without underlying leukemia or lymphoma is uncertain. A 42-year-old female with refractory lupus nephritis received three monthly cycles of fludarabine (30 mg/m2/day on Days 1-3) and cyclophosphamide (500 mg/m2 on Day 1). Three months after the last dose of fludarabine, she received 2 units of packed RBCs and 6 units of pooled random platelets, none of which were irradiated. Two weeks later, fever, rash, aminotransferase elevations, hyperbilirubinemia, and pancytopenia developed. Marrow biopsy showed severe aplasia and skin biopsy was consistent with GVHD. Allele-level HLA typing on circulating lymphocytes revealed extra HLA alleles not present in her pretreatment sample, but identical to the HLA haplotypes of an unrelated platelet donor. Treatment with antithymocyte globulin, cyclosporine, and prednisone was followed by preparatory conditioning for a PBPC transplant from an HLA-identical sibling, but the patient died of disseminated candidiasis before transplant. Fludarabine and other purine analogs are increasingly used in the treatment of disorders other than hematologic malignancy, such as autoimmune disease. The occurence of TA-GVHD after fludarabine therapy in a patient with lupus strongly suggests that this drug is sufficiently immunoablative to be an independent risk factor for TA-GVHD. Irradiation of blood components should be considered in all patients who receive fludarabine therapy. JF - Transfusion AU - Leitman, Susan F AU - Tisdale, John F AU - Bolan, Charles D AU - Popovsky, Mark A AU - Klippel, John H AU - Balow, James E AU - Boumpas, Dimitrios T AU - Illei, Gabor G AD - Department of Transfusion Medicine, National Institute of Muscuoloskeletal and Skin Disease, National Institute of Health, Bethesda, MD 20892, USA. sleitman@mail.cc.nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 1667 EP - 1671 VL - 43 IS - 12 SN - 0041-1132, 0041-1132 KW - Immunosuppressive Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Drug Therapy, Combination KW - Fatal Outcome KW - Histocompatibility Testing KW - Risk Factors KW - Humans KW - Adult KW - Female KW - Cyclophosphamide -- adverse effects KW - Vidarabine -- analogs & derivatives KW - Platelet Transfusion -- adverse effects KW - Erythrocyte Transfusion -- adverse effects KW - Lupus Erythematosus, Systemic -- drug therapy KW - Graft vs Host Disease -- epidemiology KW - Vidarabine -- adverse effects KW - Graft vs Host Disease -- etiology KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71429845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transfusion&rft.atitle=Transfusion-associated+GVHD+after+fludarabine+therapy+in+a+patient+with+systemic+lupus+erythematosus.&rft.au=Leitman%2C+Susan+F%3BTisdale%2C+John+F%3BBolan%2C+Charles+D%3BPopovsky%2C+Mark+A%3BKlippel%2C+John+H%3BBalow%2C+James+E%3BBoumpas%2C+Dimitrios+T%3BIllei%2C+Gabor+G&rft.aulast=Leitman&rft.aufirst=Susan&rft.date=2003-12-01&rft.volume=43&rft.issue=12&rft.spage=1667&rft.isbn=&rft.btitle=&rft.title=Transfusion&rft.issn=00411132&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-07 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Transfusion. 2003 Dec;43(12):1652-4 [14641857] Transfusion. 2003 Dec;43(12):1655-7 [14641858] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1990. AN - 71426809; 14640793 AB - An incidence survey of the Life Span Study (LSS) population found 1093 breast cancers among 1059 breast cancer cases diagnosed during 1950-1990. As in earlier breast cancer surveys of this population, a linear and statistically highly significant radiation dose response was found. In the analysis, particular attention was paid to modification of radiation dose response by age at exposure (e) and attained age (a). Dose-specific excess relative risk (ERR(1Sv)) decreased with increasing values of e and a. A linear dose-response model analysis, with e and a as exponential age modifiers, did not conclusively discriminate between the two variables as modifiers of dose response. A modified isotonic regression approach, requiring only that ERR(1Sv) be monotonic in age, provides a fresh perspective indicating that both e and a are important modifiers of dose response. Exposure before age 20 was associated with higher ERR(1Sv) compared to exposure at older ages, with no evidence of consistent variation by exposure age for ages under 20. ERR(1Sv) was observed to decline with increasing attained age, with by far the largest drop around age 35. Possible explanations for these observations are discussed, along with research approaches that might provide more information. JF - Radiation research AU - Land, Charles E AU - Tokunaga, Masayoshi AU - Koyama, Kojiro AU - Soda, Midori AU - Preston, Dale L AU - Nishimori, Issei AU - Tokuoka, Shoji AD - Radiation Epidemiology Branch, National Cancer Institute, Bethesda, Maryland, USA. charles_land@nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 707 EP - 717 VL - 160 IS - 6 SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - Age Factors KW - Aged, 80 and over KW - Humans KW - Adult KW - Incidence KW - Aged KW - Middle Aged KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Japan KW - Female KW - Nuclear Warfare KW - Neoplasms, Radiation-Induced -- epidemiology KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71426809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Biomedical+Engineering&rft.atitle=Novel+Technique+for+Cardiac+Electromechanical+Mapping+with+Magnetic+Resonance+Imaging+Tagging+and+an+Epicardial+Electrode+Sock&rft.au=Faris%2C+Owen+P%3BEvans%2C+Frank+J%3BEnnis%2C+Daniel+B%3BHelm%2C+Patrick+A%3BTaylor%2C+Joni+L%3BChesnick%2C+AScott%3BGuttman%2C+Michael+A%3BOzturk%2C+Cengizhan%3BMcVeigh%2C+Elliot+R&rft.aulast=Faris&rft.aufirst=Owen&rft.date=2003-04-01&rft.volume=31&rft.issue=4&rft.spage=430&rft.isbn=&rft.btitle=&rft.title=Annals+of+Biomedical+Engineering&rft.issn=00906964&rft_id=info:doi/10.1114%2F1.1560618 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-06 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Using conditional mutagenesis to study the brain. AN - 71423698; 14643079 AB - Conditional genetic modifications are used to determine how individual molecules contribute to the function of defined neuronal circuits in the mouse brain. Among various techniques for these genetic modifications, the tetracycline transactivator and the Cre-loxP systems have proved to be most successful in recent years. Here we describe the basic principles, recent developments, and potential applications of these methodologies. We discuss their impact on the study of general brain function and their use for modeling different brain disorders. JF - Biological psychiatry AU - Morozov, Alexei AU - Kellendonk, Christoph AU - Simpson, Eleanor AU - Tronche, Francois AD - Unit on Behavioral Genetics, Laboratory of Molecular Pathophysiology, Department of Health and Humans Services (AM), National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/12/01/ PY - 2003 DA - 2003 Dec 01 SP - 1125 EP - 1133 VL - 54 IS - 11 SN - 0006-3223, 0006-3223 KW - Trans-Activators KW - 0 KW - Viral Proteins KW - Cre recombinase KW - EC 2.7.7.- KW - Integrases KW - Tetracycline KW - F8VB5M810T KW - Index Medicus KW - Viral Proteins -- genetics KW - Trans-Activators -- metabolism KW - Animals KW - Learning KW - Genetic Engineering KW - Integrases -- genetics KW - Transcription, Genetic KW - Mice KW - Mice, Transgenic KW - Tetracycline -- metabolism KW - Gene Deletion KW - Mice, Knockout KW - Memory KW - Trans-Activators -- genetics KW - Gene Expression Regulation KW - Neuronal Plasticity KW - Immunohistochemistry KW - Brain -- metabolism KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71423698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Using+conditional+mutagenesis+to+study+the+brain.&rft.au=Morozov%2C+Alexei%3BKellendonk%2C+Christoph%3BSimpson%2C+Eleanor%3BTronche%2C+Francois&rft.aulast=Morozov&rft.aufirst=Alexei&rft.date=2003-12-01&rft.volume=54&rft.issue=11&rft.spage=1125&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-04 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclooxygenase inhibition in cancer prevention and treatment. AN - 71421882; 14640918 AB - Several lines of evidence suggest that the cyclooxygenase enzymes (specifically COX-2) might be an important molecular target for the intervention of cancer at both early and late stages of some cancers, providing an opportunity for both cancer prevention and therapy. COX-2 is overexpressed during carcinogenesis, and appears to have a role in both tumour initiation and promotion and is amenable to intervention. This review discusses the importance of COX modulation via non-specific, as well as COX-2 specific COX inhibitors (NSAIDs and COX-2 selective inhibitors [COXIB]). A brief discussion on the pharmacoeconomic considerations of NSAID and COXIB use and safety issues that have recently been the focus of debate, will be presented. JF - Expert opinion on pharmacotherapy AU - Anderson, William F AU - Umar, Asad AU - Hawk, Ernest T AD - Gastrointestinal & Other Cancers Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, EPN, Room 2141, 6130 Executive Boulevard, Bethesda, MD 20892-7317, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 2193 EP - 2204 VL - 4 IS - 12 SN - 1465-6566, 1465-6566 KW - Anticarcinogenic Agents KW - 0 KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Isoenzymes -- antagonists & inhibitors KW - Isoenzymes -- biosynthesis KW - Humans KW - Clinical Trials as Topic KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Isoenzymes -- genetics KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Cyclooxygenase Inhibitors -- adverse effects KW - Neoplasms -- enzymology KW - Anticarcinogenic Agents -- therapeutic use KW - Anticarcinogenic Agents -- pharmacology KW - Neoplasms -- prevention & control KW - Anticarcinogenic Agents -- adverse effects KW - Cyclooxygenase Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71421882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cyclooxygenase+inhibition+in+cancer+prevention+and+treatment.&rft.au=Anderson%2C+William+F%3BUmar%2C+Asad%3BHawk%2C+Ernest+T&rft.aulast=Anderson&rft.aufirst=William&rft.date=2003-12-01&rft.volume=4&rft.issue=12&rft.spage=2193&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 - 2004-03-12 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. AN - 71419774; 14657318 AB - To evaluate the effect of using the ferumoxides-poly-l-lysine (PLL) complex for magnetic cell labeling on the long-term viability, function, metabolism, and iron utilization of mammalian cells. PLL was incubated with ferumoxides for 60 minutes, incompletely coating the superparamagnetic iron oxide (SPIO) through electrostatic interactions. Cells were coincubated overnight with the ferumoxides-PLL complex, and iron uptake, cell viability, apoptosis indexes, and reactive oxygen species formation were evaluated. The disappearance or the life span of the detectable iron nanoparticles in cells was also evaluated. The iron concentrations in the media also were assessed at different time points. Data were expressed as the mean +/- 1 SD, and one-way analysis of variance and the unpaired Student t test were used to test for significant differences. Intracytoplasmic nanoparticles were stained with Prussian blue when the ferumoxides-PLL complex had magnetically labeled the human mesenchymal stem and HeLa cells. The long-term viability, growth rate, and apoptotic indexes of the labeled cells were unaffected by the endosomal incorporation of SPIO, as compared with these characteristics of the nonlabeled cells. In nondividing human mesenchymal stem cells, endosomal iron nanoparticles could be detected after 7 weeks; however, in rapidly dividing cells, intracellular iron had disappeared by five to eight divisions. A nonsignificant transient increase in reactive oxygen species production was seen in the human mesenchymal stem and HeLa cell lines. Labeled human mesenchymal stem cells did not differentiate to other lineage. A significant increase in iron concentration was observed in both the human mesenchymal stem and HeLa cell media at day 7. Magnetic cellular labeling with the ferumoxides-PLL complex had no short- or long-term toxic effects on tumor or stem cells. JF - Radiology AU - Arbab, Ali S AU - Bashaw, Lindsey A AU - Miller, Bradley R AU - Jordan, Elaine K AU - Lewis, Bobbi K AU - Kalish, Heather AU - Frank, Joseph A AD - Experimental Neuroimaging Section, Laboratory of Diagnostic Radiology Research, National Institutes of Health, 10 Center Dr, Rm B1N256, Bethesda, MD 20892, USA. saali@cc.nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 838 EP - 846 VL - 229 IS - 3 SN - 0033-8419, 0033-8419 KW - Contrast Media KW - 0 KW - Dextrans KW - Ferrocyanides KW - Magnetite Nanoparticles KW - Oxides KW - Reactive Oxygen Species KW - Polylysine KW - 25104-18-1 KW - Iron KW - E1UOL152H7 KW - ferumoxides KW - G6N3J05W84 KW - ferric ferrocyanide KW - TLE294X33A KW - Ferrosoferric Oxide KW - XM0M87F357 KW - Abridged Index Medicus KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Polylysine -- pharmacokinetics KW - Apoptosis KW - Cells, Cultured KW - Particle Size KW - Humans KW - Polylysine -- toxicity KW - Cell Survival KW - Magnetic Resonance Imaging KW - HeLa Cells -- metabolism KW - Contrast Media -- pharmacokinetics KW - Contrast Media -- toxicity KW - Iron -- pharmacokinetics KW - Oxides -- pharmacokinetics KW - Stem Cells -- physiology KW - Stem Cells -- metabolism KW - Oxides -- toxicity KW - Iron -- toxicity KW - HeLa Cells -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71419774?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiology&rft.atitle=Characterization+of+biophysical+and+metabolic+properties+of+cells+labeled+with+superparamagnetic+iron+oxide+nanoparticles+and+transfection+agent+for+cellular+MR+imaging.&rft.au=Arbab%2C+Ali+S%3BBashaw%2C+Lindsey+A%3BMiller%2C+Bradley+R%3BJordan%2C+Elaine+K%3BLewis%2C+Bobbi+K%3BKalish%2C+Heather%3BFrank%2C+Joseph+A&rft.aulast=Arbab&rft.aufirst=Ali&rft.date=2003-12-01&rft.volume=229&rft.issue=3&rft.spage=838&rft.isbn=&rft.btitle=&rft.title=Radiology&rft.issn=00338419&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-12 N1 - Date created - 2003-12-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Radiology. 2003 Dec;229(3):615-6 [14657295] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity and carcinogenicity of Elmiron in F344/N rats and B6C3F1 mice following 2 years of gavage administration. AN - 71419662; 14508637 AB - Elmiron (sodium pentosan polysulfate) is used for the relief of urinary bladder pain associated with interstitial cystitis. The National Toxicology Program (NTP) tested this compound because of its orphan drug status and lack of information about its chronic toxicity and carcinogenicity. Groups of 50 male and 50 female F344/N rats were given Elmiron in de-ionized water by gavage at doses of 0, 14, 42, or 126 mg/kg to males and 0, 28, 84, or 252 mg/kg to females once daily, 5 days per week, for up to 2 years. The same numbers of male and female B6C3F1 mice were dosed similarly with 0, 56, 168, or 504 mg/kg. Elmiron administration produced no effect on the body weight of rats, male mice, or low- and mid-dose groups of female mice. The body weights of the high-dose female mice were significantly decreased relative to those of controls. Pairwise comparison showed that survival of all dosed groups of rats and mice was similar to that of the controls. Elmiron was not carcinogenic in F344/N rats. An increased incidence of liver hemangiosarcoma provided evidence of some carcinogenic activity for Elmiron in male B6C3F1 mice. Increased incidences of liver hemangiosarcoma, hepatocellular neoplasms (predominantly adenomas), and malignant lymphomas revealed carcinogenic activity of Elmiron in female B6C3F1 mice. Elmiron administration produced elevated occurrences of nonneoplastic lesions, such as vacuolated histiocytes in the rectum, lung, spleen (males only), and mesenteric lymph node in rats and liver, rectum, mesenteric lymph node, and spleen in mice. Myxomatous change, chronic inflammation, and squamous metaplasia (mice only) were observed in the large intestine, and lymphohistiocytic hyperplasia was found to be increased in the spleen of rats of both sexes treated with the highest dose. In the latter lesion, the histiocytes contained pale, finely granular cytoplasm and were not considered to represent the same change as the vacuolated histiocytes seen in the mesenteric lymph node and rectum. Under the conditions of these 2-year studies, Elmiron was carcinogenic to mice but not rats. JF - Archives of toxicology AU - Abdo, Kamal M AU - Johnson, Jerry D AU - Nyska, Abraham AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, MD EC-35, PO Box 12233, Research Triangle Park, NC 27709-9998, USA. abdok@niehs.nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 702 EP - 711 VL - 77 IS - 12 SN - 0340-5761, 0340-5761 KW - Anticoagulants KW - 0 KW - Pentosan Sulfuric Polyester KW - 37300-21-3 KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Dose-Response Relationship, Drug KW - Mice KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Body Weight -- drug effects KW - Carcinogenicity Tests KW - Time Factors KW - Species Specificity KW - Female KW - Male KW - Survival Analysis KW - Anticoagulants -- toxicity KW - Pentosan Sulfuric Polyester -- administration & dosage KW - Pentosan Sulfuric Polyester -- toxicity KW - Anticoagulants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71419662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+toxicology&rft.atitle=Toxicity+and+carcinogenicity+of+Elmiron+in+F344%2FN+rats+and+B6C3F1+mice+following+2+years+of+gavage+administration.&rft.au=Abdo%2C+Kamal+M%3BJohnson%2C+Jerry+D%3BNyska%2C+Abraham&rft.aulast=Abdo&rft.aufirst=Kamal&rft.date=2003-12-01&rft.volume=77&rft.issue=12&rft.spage=702&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology&rft.issn=03405761&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-25 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucagon-like peptide 1 modulates calcium responses to glutamate and membrane depolarization in hippocampal neurons. AN - 71417589; 14622093 AB - Glucagon-like peptide 1 (GLP-1) activates receptors coupled to cAMP production and calcium influx in pancreatic cells, resulting in enhanced glucose sensitivity and insulin secretion. Despite evidence that the GLP-1 receptor is present and active in neurons, little is known of the roles of GLP-1 in neuronal physiology. As GLP-1 modulates calcium homeostasis in pancreatic beta cells, and because calcium plays important roles in neuronal plasticity and neurodegenerative processes, we examined the effects of GLP-1 on calcium regulation in cultured rat hippocampal neurons. When neurons were pre-treated with GLP-1, calcium responses to glutamate and membrane depolarization were attenuated. Whole-cell patch clamp analyses showed that glutamate-induced currents and currents through voltage-dependent calcium channels were significantly decreased in neurons pre-treated with GLP-1. Pre-treatment of neurons with GLP-1 significantly decreased their vulnerability to death induced by glutamate. Acute application of GLP-1 resulted in a transient elevation of intracellular calcium levels, consistent with the established effects of GLP-1 on cAMP production and activation of cAMP response element-binding protein. Collectively, our findings suggest that, by modulating calcium responses to glutamate and membrane depolarization, GLP-1 may play important roles in regulating neuronal plasticity and cell survival. JF - Journal of neurochemistry AU - Gilman, Charles P AU - Perry, TracyAnn AU - Furukawa, Katsotoshi AU - Grieg, Nigel H AU - Egan, Josephine M AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 1137 EP - 1144 VL - 87 IS - 5 SN - 0022-3042, 0022-3042 KW - Calcium Channels KW - 0 KW - Neuroprotective Agents KW - Neurotoxins KW - Peptide Fragments KW - Protein Precursors KW - Glutamic Acid KW - 3KX376GY7L KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Calcium Channels -- metabolism KW - Patch-Clamp Techniques KW - Cells, Cultured KW - Calcium Channels -- drug effects KW - Neuroprotective Agents -- metabolism KW - Neurotoxins -- pharmacology KW - Cell Death -- drug effects KW - Neuroprotective Agents -- pharmacology KW - Peptide Fragments -- metabolism KW - Protein Precursors -- metabolism KW - Neurons -- drug effects KW - Glucagon -- pharmacology KW - Glutamic Acid -- pharmacology KW - Protein Precursors -- pharmacology KW - Calcium -- metabolism KW - Glucagon -- metabolism KW - Hippocampus -- cytology KW - Neurons -- cytology KW - Peptide Fragments -- pharmacology KW - Neurons -- physiology KW - Cell Membrane -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71417589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Muscarinic+receptor+subtypes+mediating+central+and+peripheral+antinociception+studied+with+muscarinic+receptor+knockout+mice%3A+a+review.&rft.au=Wess%2C+J%C3%BCrgen%3BDuttaroy%2C+Alokesh%3BGomeza%2C+Jesus%3BZhang%2C+Weilie%3BYamada%2C+Masahisa%3BFelder%2C+Christian+C%3BBernardini%2C+Nadia%3BReeh%2C+Peter+W&rft.aulast=Wess&rft.aufirst=J%C3%BCrgen&rft.date=2003-03-28&rft.volume=72&rft.issue=18-19&rft.spage=2047&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-18 N1 - Date created - 2003-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hyperforin-containing extracts of St John's wort fail to alter gene transcription in brain areas involved in HPA axis control in a long-term treatment regimen in rats. AN - 71413661; 12865894 AB - We previously showed that a methanolic extract of St John's wort (SJW) (Hypericum) and hypericin, one of its active constituents, both have delayed regulation of genes that are involved in the control of the hypothalamic-pituitary-adrenal (HPA) axis. Hyperforin, another constituent of SJW, is active in vitro and has been proposed to be the active constituent for therapeutic efficacy in depression. We therefore examined if hyperforin has delayed effects on HPA axis control centers similar to those of Hypericum and hypericin. We used in situ hybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) oral administration of two hyperforin preparations, fluoxetine (positive control), and haloperidol (negative control) on the expression of genes involved in the regulation of the HPA axis. Fluoxetine (10 mg/kg) given daily for 8 weeks, but not 2 weeks, significantly decreased levels of corticotropin-releasing hormone (CRH) mRNA by 22% in the paraventricular nucleus (PVN) of the hypothalamus and tyrosine hydroxylase (TH) mRNA by 23% in the locus coeruleus. Fluoxetine increased levels of mineralocorticoid (MR) (17%), glucocorticoid (GR) (18%), and 5-HT(1A) receptor (21%) mRNAs in the hippocampus at 8, but not 2, weeks. Comparable to haloperidol (1 mg/kg), neither the hyperforin-rich CO(2) extract (27 mg/kg) nor hyperforin-trimethoxybenzoate (8 mg/kg) altered mRNA levels in brain structures relevant for HPA axis control at either time point. These data suggest that hyperforin and hyperforin derivatives are not involved in the regulation of genes that control HPA axis function. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Butterweck, Veronika AU - Winterhoff, Hilke AU - Herkenham, Miles AD - Section on Functional Neuroanatomy, NIMH, Bethesda, MD 20892, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 2160 EP - 2168 VL - 28 IS - 12 SN - 0893-133X, 0893-133X KW - Anti-Bacterial Agents KW - 0 KW - Antidepressive Agents KW - Bridged Bicyclo Compounds KW - Phosphoproteins KW - Plant Extracts KW - RNA, Messenger KW - Receptors, Glucocorticoid KW - Receptors, Mineralocorticoid KW - Terpenes KW - Receptor, Serotonin, 5-HT1A KW - 112692-38-3 KW - Pro-Opiomelanocortin KW - 66796-54-1 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Phloroglucinol KW - DHD7FFG6YS KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - hyperforin KW - RM741E34FP KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Animals KW - Drug Interactions KW - Adrenal Glands -- drug effects KW - Receptors, Mineralocorticoid -- metabolism KW - Receptors, Glucocorticoid -- metabolism KW - Phloroglucinol -- analogs & derivatives KW - Rats KW - Corticosterone -- blood KW - In Situ Hybridization -- methods KW - Time Factors KW - Male KW - Organ Size -- drug effects KW - Adrenocorticotropic Hormone -- blood KW - Phosphoproteins -- metabolism KW - Tyrosine 3-Monooxygenase -- metabolism KW - Phosphoproteins -- genetics KW - Pro-Opiomelanocortin -- genetics KW - Radioimmunoassay -- methods KW - Pro-Opiomelanocortin -- metabolism KW - Plant Extracts -- pharmacology KW - RNA, Messenger -- metabolism KW - Receptor, Serotonin, 5-HT1A -- metabolism KW - Body Weight -- drug effects KW - Immunohistochemistry KW - Hypothalamo-Hypophyseal System -- drug effects KW - Transcription, Genetic -- drug effects KW - Antidepressive Agents -- pharmacology KW - Hypericum -- chemistry KW - Brain -- drug effects KW - Brain -- anatomy & histology KW - Anti-Bacterial Agents -- pharmacology KW - Pituitary-Adrenal System -- metabolism KW - Hypothalamo-Hypophyseal System -- metabolism KW - Brain -- metabolism KW - Terpenes -- pharmacology KW - Pituitary-Adrenal System -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71413661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hyperforin-containing+extracts+of+St+John%27s+wort+fail+to+alter+gene+transcription+in+brain+areas+involved+in+HPA+axis+control+in+a+long-term+treatment+regimen+in+rats.&rft.au=Butterweck%2C+Veronika%3BWinterhoff%2C+Hilke%3BHerkenham%2C+Miles&rft.aulast=Butterweck&rft.aufirst=Veronika&rft.date=2003-12-01&rft.volume=28&rft.issue=12&rft.spage=2160&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 - 2004-02-10 N1 - Date created - 2003-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative drug disposition, urinary pharmacokinetics, and renal effects of multilamellar liposomal nystatin and amphotericin B deoxycholate in rabbits. AN - 71397459; 14638502 AB - The comparative drug dispositions, urinary pharmacokinetics, and effects on renal function of multilamellar liposomal nystatin (LNYS; Nyotran) and amphotericin B deoxycholate (DAMB; Fungizone) were studied in rabbits. Drug concentrations were determined by high-performance liquid chromatography as total concentrations of LNYS and DAMB. In comparison to a standard dose of 1 mg of DAMB/kg of body weight, therapeutic dosages of LNYS, i.e., 2, 4, and 6 mg/kg, resulted in escalating maximum concentrations (Cmax) (17 to 56 microg/ml for LNYS versus 3.36 microg/ml for DAMB; P or =10-fold-higher Cmax (16 to 10 microg/ml for LNYS versus 0.96 microg/ml for DAMB; P=0.015) and a 4- to 7-fold-greater AUC(0-24) (63 to 35 microg.h/ml for LNYS versus 8.9 microg.h/ml for DAMB; P=0.015) following the administration of LNYS, with a dose-dependent decrease in the dose-normalized AUC(0-24) in urine (P=0.001) and a trend toward a dose-dependent decrease in renal clearance. Except for the kidneys, the mean concentrations of LNYS in liver, spleen, and lung 24 h after dosing were severalfold lower than those after administration of DAMB (P, <0.002 to <0.001). Less than 1% each of the total dose of LNYS was recovered from the kidneys, liver, spleen, and lungs; in contrast, a quarter of the total dose was recovered from the livers of DAMB-treated animals. LNYS had dose-dependent effects on glomerular filtration and distal, but not proximal, renal tubular function which did not exceed those of DAMB at the highest investigated dosage of 6 mg/kg. The results of this experimental study demonstrate fundamental differences in the dispositions of LNYS and DAMB. Based on its enhanced urinary exposure, LNYS may offer a therapeutic advantage in systemic fungal infections involving the upper and lower urinary tracts that require therapy with antifungal polyenes. JF - Antimicrobial agents and chemotherapy AU - Groll, Andreas H AU - Mickiene, Diana AU - Petraitis, Vidmantas AU - Petraitiene, Ruta AU - Alfaro, Raul M AU - King, Christine AU - Piscitelli, Stephen C AU - Walsh, Thomas J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, 20892, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 3917 EP - 3925 VL - 47 IS - 12 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Drug Combinations KW - Electrolytes KW - Liposomes KW - beta 2-Microglobulin KW - Deoxycholic Acid KW - 005990WHZZ KW - Nystatin KW - 1400-61-9 KW - Amphotericin B KW - 7XU7A7DROE KW - amphotericin B, deoxycholate drug combination KW - 87687-70-5 KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Kidney Function Tests KW - Animals KW - Creatinine -- metabolism KW - Area Under Curve KW - beta 2-Microglobulin -- metabolism KW - Rabbits KW - Tissue Distribution KW - Urodynamics -- drug effects KW - Models, Biological KW - Electrolytes -- urine KW - Female KW - Deoxycholic Acid -- pharmacokinetics KW - Nystatin -- pharmacokinetics KW - Antifungal Agents -- pharmacokinetics KW - Antifungal Agents -- adverse effects KW - Nystatin -- administration & dosage KW - Deoxycholic Acid -- adverse effects KW - Amphotericin B -- pharmacokinetics KW - Deoxycholic Acid -- administration & dosage KW - Amphotericin B -- adverse effects KW - Amphotericin B -- administration & dosage KW - Antifungal Agents -- administration & dosage KW - Nystatin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71397459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparative+drug+disposition%2C+urinary+pharmacokinetics%2C+and+renal+effects+of+multilamellar+liposomal+nystatin+and+amphotericin+B+deoxycholate+in+rabbits.&rft.au=Groll%2C+Andreas+H%3BMickiene%2C+Diana%3BPetraitis%2C+Vidmantas%3BPetraitiene%2C+Ruta%3BAlfaro%2C+Raul+M%3BKing%2C+Christine%3BPiscitelli%2C+Stephen+C%3BWalsh%2C+Thomas+J&rft.aulast=Groll&rft.aufirst=Andreas&rft.date=2003-12-01&rft.volume=47&rft.issue=12&rft.spage=3917&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 - 2004-01-13 N1 - Date created - 2003-11-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Antimicrob Agents Chemother. 1999 Nov;43(11):2592-9 [10543734] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] J Chromatogr B Biomed Sci Appl. 1999 Nov 26;735(1):51-62 [10630890] Antimicrob Agents Chemother. 2000 Apr;44(4):950-7 [10722496] J Infect Dis. 2000 Jul;182(1):274-82 [10882607] Am J Kidney Dis. 2000 Aug;36(2):238-49 [10922301] Ann Intern Med. 1964 Aug;61:175-87 [14204856] Antimicrob Agents Chemother. 1987 Dec;31(12):1897-900 [3439798] Antimicrob Agents Chemother. 1987 Dec;31(12):1901-3 [3439799] Drug Saf. 1990 Mar-Apr;5(2):94-108 [2182052] Pediatr Nephrol. 1988 Apr;2(2):183-9 [3153009] Pharm Res. 1993 Jul;10(7):1093-5 [8378254] Antimicrob Agents Chemother. 1994 Feb;38(2):223-7 [8192447] Antimicrob Agents Chemother. 1994 Apr;38(4):713-8 [8031034] J Am Soc Nephrol. 1995 Aug;6(2):154-64 [7579079] Cancer. 1995 Dec 15;76(12):2557-64 [8625085] Clin Microbiol Rev. 1996 Oct;9(4):512-31 [8894350] Eur J Clin Microbiol Infect Dis. 1997 Jan;16(1):81-92 [9063678] Antimicrob Agents Chemother. 1997 Sep;41(9):1871-5 [9303376] Antimicrob Agents Chemother. 1997 Oct;41(10):2238-43 [9333054] Adv Pharmacol. 1998;44:343-500 [9547888] Antimicrob Agents Chemother. 1998 Jun;42(6):1412-6 [9624486] N Engl J Med. 1999 Mar 11;340(10):764-71 [10072411] Antimicrob Agents Chemother. 1999 May;43(5):1264-6 [10223948] J Antimicrob Chemother. 1999 Jan;43(1):95-103 [10381106] Antimicrob Agents Chemother. 1999 Oct;43(10):2463-7 [10508025] J Antimicrob Chemother. 1999 Sep;44(3):397-401 [10511410] Science. 1950 Oct 13;112(2911):423 [14781786] Clin Infect Dis. 1999 Dec;29(6):1402-7 [10585786] Antimicrob Agents Chemother. 2000 Oct;44(10):2887-90 [10991881] Am J Med. 2001 Nov;111(7):528-34 [11705428] Antimicrob Agents Chemother. 2002 Mar;46(3):828-33 [11850268] Antimicrob Agents Chemother. 2002 Mar;46(3):834-40 [11850269] J Clin Microbiol. 2002 Apr;40(4):1406-12 [11923365] Bacteriol Rev. 1973 Sep;37(3):166-96 [4202146] J Pharmacokinet Biopharm. 1978 Apr;6(2):165-75 [671222] Antimicrob Agents Chemother. 1979 May;15(5):716-22 [393163] J Membr Biol. 1984;80(3):257-69 [6094818] Arch Biochem Biophys. 1963 Aug;102:180-8 [14061721] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational cancer among women: where have we been and where are we going? AN - 71395661; 14635233 AB - Studies of occupational exposures have been a fruitful area of research for identifying carcinogens. Some of the early observations, such as increased risk of breast cancer among nuns and bone cancer among radium dial workers, were made among women. Recent research on cancer among women has shown increased risks of cancer in many industries and occupations. Estimates that 1% of cancer among women is attributable to occupation are based on research conducted mainly in the 1970s among men in developed countries. These studies do not reflect the dramatic changes in the participation of women in the workplace or the patterns of employment of women in developing countries. The proportion of women in the paid workforce, the amounts and types of unpaid labor, the distribution of women by economy sector, the scale of the workplaces, the allowable exposure levels in the workplace, and implementation of controls have changed over time and vary internationally. Occupational cancer researchers need to expand their focus on women, increase activities in developing countries, include newly created industries, use sophisticated exposure assessment methods, and, where appropriate, incorporate molecular epidemiologic techniques to discover new occupational carcinogens and to identify where better control measures are needed. JF - American journal of industrial medicine AU - Zahm, Shelia Hoar AU - Blair, Aaron AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland 20892-7242, USA. Zahm@mail.nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 565 EP - 575 VL - 44 IS - 6 SN - 0271-3586, 0271-3586 KW - Carcinogens, Environmental KW - 0 KW - Index Medicus KW - Sex Factors KW - Epidemiologic Studies KW - Humans KW - Male KW - Female KW - Occupational Exposure KW - Carcinogens, Environmental -- adverse effects KW - Occupational Diseases -- etiology KW - Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology KW - Developing Countries KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71395661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Sequence+context+at+human+single+nucleotide+polymorphisms%3A+overrepresentation+of+CpG+dinucleotide+at+polymorphic+sites+and+suppression+of+variation+in+CpG+islands.&rft.au=Tomso%2C+Daniel+J%3BBell%2C+Douglas+A&rft.aulast=Tomso&rft.aufirst=Daniel&rft.date=2003-03-21&rft.volume=327&rft.issue=2&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-18 N1 - Date created - 2003-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interference with transforming growth factor-beta/ Smad3 signaling results in accelerated healing of wounds in previously irradiated skin. AN - 71394234; 14633599 AB - Transforming growth factor (TGF)-beta regulates many aspects of wound repair including inflammation, chemotaxis, and deposition of extracellular matrix. We previously showed that epithelialization of incisional wounds is accelerated in mice null for Smad3, a key cytoplasmic mediator of TGF-beta signaling. Here, we investigated the effects of loss of Smad3 on healing of wounds in skin previously exposed to ionizing radiation, in which scarring fibrosis complicates healing. Cutaneous wounds made in Smad3-null mice 6 weeks after irradiation showed decreased wound widths, enhanced epithelialization, and reduced numbers of neutrophils and myofibroblasts compared to wounds in irradiated wild-type littermates. Differences in breaking strength of wild-type and Smad3-null wounds were not significant. As shown previously for neutrophils, chemotaxis of primary dermal fibroblasts to TGF-beta required Smad3, but differentiation of fibroblasts to myofibroblasts by TGF-beta was independent of Smad3. Previous irradiation-enhanced induction of connective tissue growth factor mRNA in wild-type, but not Smad3-null fibroblasts, suggested that this may contribute to the heightened scarring in irradiated wild-type skin as demonstrated by Picrosirius red staining. Overall, the data suggest that attenuation of Smad3 signaling might improve the healing of wounds in previously irradiated skin commensurate with an inhibition of fibrosis. JF - The American journal of pathology AU - Flanders, Kathleen C AU - Major, Christopher D AU - Arabshahi, Alidad AU - Aburime, Ekinadese E AU - Okada, Miya H AU - Fujii, Makiko AU - Blalock, Timothy D AU - Schultz, Gregory S AU - Sowers, Anastasia AU - Anzano, Mario A AU - Mitchell, James B AU - Russo, Angelo AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis and the Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 21201, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 2247 EP - 2257 VL - 163 IS - 6 SN - 0002-9440, 0002-9440 KW - Ctgf protein, mouse KW - 0 KW - DNA-Binding Proteins KW - Immediate-Early Proteins KW - Intercellular Signaling Peptides and Proteins KW - Smad3 Protein KW - Smad3 protein, mouse KW - Tgfb1 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Connective Tissue Growth Factor KW - 139568-91-5 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Fibroblasts -- drug effects KW - Immediate-Early Proteins -- metabolism KW - Tensile Strength KW - Mice KW - Mice, Knockout KW - Cicatrix -- prevention & control KW - Epithelium -- physiopathology KW - Fibroblasts -- pathology KW - Cicatrix -- etiology KW - Intercellular Signaling Peptides and Proteins -- metabolism KW - Transforming Growth Factor beta -- pharmacology KW - Trans-Activators -- metabolism KW - Signal Transduction -- physiology KW - Skin -- radiation effects KW - Skin -- physiopathology KW - Wound Healing KW - Skin -- pathology KW - Transforming Growth Factor beta -- metabolism KW - Radiation Injuries -- pathology KW - Radiation Injuries -- complications KW - Radiation Injuries -- physiopathology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71394234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Interference+with+transforming+growth+factor-beta%2F+Smad3+signaling+results+in+accelerated+healing+of+wounds+in+previously+irradiated+skin.&rft.au=Flanders%2C+Kathleen+C%3BMajor%2C+Christopher+D%3BArabshahi%2C+Alidad%3BAburime%2C+Ekinadese+E%3BOkada%2C+Miya+H%3BFujii%2C+Makiko%3BBlalock%2C+Timothy+D%3BSchultz%2C+Gregory+S%3BSowers%2C+Anastasia%3BAnzano%2C+Mario+A%3BMitchell%2C+James+B%3BRusso%2C+Angelo%3BRoberts%2C+Anita+B&rft.aulast=Flanders&rft.aufirst=Kathleen&rft.date=2003-12-01&rft.volume=163&rft.issue=6&rft.spage=2247&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-15 N1 - Date created - 2003-11-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1996 Apr 26;271(17):10188-93 [8626581] Exp Mol Pathol. 1995 Jun;62(3):160-5 [8612719] Nat Cell Biol. 1999 Sep;1(5):260-6 [10559937] Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):49-58 [10708952] Int J Radiat Oncol Biol Phys. 2000 May 1;47(2):277-90 [10802350] Mol Genet Metab. 2000 Sep-Oct;71(1-2):276-92 [11001822] J Biol Chem. 2001 Apr 6;276(14):10594-601 [11152469] J Biol Chem. 2001 May 18;276(20):17058-62 [11279127] J Biol Chem. 2001 Jun 8;276(23):19945-53 [11262418] Chest. 2001 Jul;120(1 Suppl):43S-47S [11451911] EMBO J. 2001 Oct 1;20(19):5361-72 [11574468] Arch Biochem Biophys. 2001 Nov 1;395(1):103-12 [11673871] Am J Pathol. 2002 Mar;160(3):1057-68 [11891202] J Biol Chem. 2002 Sep 27;277(39):36433-42 [12110667] Science. 1983 Mar 18;219(4590):1329-31 [6572416] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 [6326095] J Exp Med. 1987 Jan 1;165(1):251-6 [3491869] Radiat Res. 1988 Oct;116(1):135-44 [2973074] Nucleic Acids Res. 1990 May 25;18(10):3059 [2349108] J Clin Endocrinol Metab. 1991 Feb;72(2):496-502 [1899424] Cell. 2000 Oct 13;103(2):295-309 [11057902] Arch Otolaryngol Head Neck Surg. 1996 Feb;122(2):171-7 [8630211] Int J Radiat Biol. 1996 Sep;70(3):351-60 [8800206] Science. 1997 Apr 4;276(5309):75-81 [9082989] Radiother Oncol. 1997 Feb;42(2):99-106 [9106919] Cytokine Growth Factor Rev. 1997 Sep;8(3):171-9 [9462483] Am J Pathol. 1998 Feb;152(2):485-93 [9466575] J Biol Chem. 1999 Jan 29;274(5):2732-42 [9915804] EMBO J. 1999 Mar 1;18(5):1280-91 [10064594] N Engl J Med. 1999 Sep 2;341(10):738-46 [10471461] EMBO J. 1999 Oct 1;18(19):5205-15 [10508154] FASEB J. 1999 Oct;13(13):1774-86 [10506580] J Invest Dermatol. 1991 Sep;97(3):430-4 [1875042] Growth Factors. 1991;5(4):295-304 [1777238] Radiat Res. 1993 Apr;134(1):63-70 [8475255] J Dermatol Surg Oncol. 1993 Jun;19(6):564-70 [8509518] Clin Plast Surg. 1993 Jul;20(3):435-53 [8324983] J Clin Invest. 1993 Dec;92(6):2841-9 [8254038] Clin Dermatol. 1994 Jan-Mar;12(1):57-70 [8180946] Int J Radiat Biol. 1995 Sep;68(3):301-9 [7561390] Ann Trop Med Parasitol. 1999 Apr;93(3):265-72 [10562828] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Id4 regulates mammary epithelial cell growth and differentiation and is overexpressed in rat mammary gland carcinomas. AN - 71394152; 14633621 AB - Id4 belongs to a family of helix-loop-helix (HLH) proteins that impact cellular growth and differentiation via regulation of basic HLH transcription factors. Herein the rat Id4 gene was cloned (GenBank Accession No. AF468681). The expression of rat Id4 was examined in rat mammary gland tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen found in the human diet. By real-time polymerase chain reaction analysis, relative expression of Id4 mRNA in carcinomas, adenomas, and normal tissue was 27, 6, and 1, respectively. Immunohistochemical analysis indicated statistically elevated nuclear expression for Id4 protein in carcinomas in comparison to adenomas and normal mammary gland. In carcinomas, Id4 nuclear expression was positively correlated with proliferation, invasiveness, and tumor weight (Fisher Exact Test or Spearman Correlation, P < 0.05). The consequence of enforced expression of Id4 on mammary epithelial cell proliferation, differentiation, and growth in soft agar was examined in HC11 cells, a well-characterized model for studying various aspects of mammary epithelial cell biology. After transient and stable transfection of HC11 cells, Id4 overexpression increased cell proliferation and inhibited lactogenic hormone-mediated differentiation as revealed by inhibition of beta-casein promoter activity and beta-casein expression. In addition, enforced expression of Id4 in HC11 cells induced a statistically significant increase in colony growth in soft agar. The results implicate Id4 in rat mammary gland carcinogenesis and suggest that Id4 may contribute to carcinogenesis by inhibiting mammary epithelial cell differentiation and stimulating mammary epithelial cell growth. JF - The American journal of pathology AU - Shan, Liang AU - Yu, Minshu AU - Qiu, Cunping AU - Snyderwine, Elizabeth G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute Center for Cancer Research, National Institutes of Health, Bethesda, Maryland 20892-4262, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 2495 EP - 2502 VL - 163 IS - 6 SN - 0002-9440, 0002-9440 KW - Carcinogens KW - 0 KW - DNA-Binding Proteins KW - ID4 protein, human KW - Idb4 protein, rat KW - Imidazoles KW - Inhibitor of Differentiation Proteins KW - Transcription Factors KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Base Sequence -- genetics KW - Amino Acid Sequence -- genetics KW - Cell Differentiation KW - Genome KW - Cloning, Molecular KW - Rats KW - Rats, Sprague-Dawley KW - Epithelial Cells -- cytology KW - Molecular Sequence Data KW - Female KW - Cell Division KW - Mammary Neoplasms, Experimental -- chemically induced KW - Adenoma -- metabolism KW - Mammary Glands, Animal -- cytology KW - Transcription Factors -- metabolism KW - DNA-Binding Proteins -- genetics KW - Mammary Neoplasms, Experimental -- metabolism KW - Carcinoma -- metabolism KW - Transcription Factors -- genetics KW - DNA-Binding Proteins -- metabolism KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71394152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Id4+regulates+mammary+epithelial+cell+growth+and+differentiation+and+is+overexpressed+in+rat+mammary+gland+carcinomas.&rft.au=Shan%2C+Liang%3BYu%2C+Minshu%3BQiu%2C+Cunping%3BSnyderwine%2C+Elizabeth+G&rft.aulast=Shan&rft.aufirst=Liang&rft.date=2003-12-01&rft.volume=163&rft.issue=6&rft.spage=2495&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-15 N1 - Date created - 2003-11-24 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF468681; GENBANK N1 - SuppNotes - Cited By: Cancer Res. 2000 Mar 1;60(5):1332-40 [10728695] Am J Pathol. 1999 Sep;155(3):815-22 [10487839] J Neurosci. 2000 Oct 15;20(20):7648-56 [11027225] J Cell Sci. 2000 Nov;113 ( Pt 22):3897-905 [11058077] EMBO J. 2000 Nov 1;19(21):5772-81 [11060028] Cancer Res. 2000 Nov 1;60(21):5929-33 [11085505] Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):130-5 [11136250] J Biol Chem. 2001 Apr 13;276(15):11852-8 [11278321] Endocrinology. 2001 May;142(5):1727-36 [11316735] Cancer Res. 2001 Aug 15;61(16):6008-11 [11507043] J Biol Chem. 2001 Oct 19;276(42):39213-9 [11498533] Cancer Res. 2001 Dec 15;61(24):8803-10 [11751402] Cell Growth Differ. 2001 Dec;12(12):649-56 [11751460] Oncogene. 2001 Dec 20;20(58):8290-8 [11840321] Oncogene. 2001 Dec 20;20(58):8308-16 [11840323] Oncogene. 2001 Dec 20;20(58):8326-33 [11840325] Oncogene. 2001 Dec 20;20(58):8334-41 [11840326] J Urol. 2002 Jun;167(6):2598-602 [11992094] Proc Natl Acad Sci U S A. 2002 May 28;99(11):7560-5 [12032322] Mol Carcinog. 2002 Aug;34(4):211-8 [12203372] Carcinogenesis. 2002 Oct;23(10):1561-8 [12376462] Oncogene. 2003 Feb 27;22(8):1253-60 [12606953] J Natl Cancer Inst. 1978 Dec;61(6):1439-49 [102856] EMBO J. 1988 Jul;7(7):2089-95 [3416834] Lab Invest. 1990 Mar;62(3):244-78 [2107367] Nucleic Acids Res. 1994 Mar 11;22(5):749-55 [8139914] Carcinogenesis. 1994 Nov;15(11):2429-33 [7955086] Mol Cell Biol. 1995 Jun;15(6):3398-404 [7760836] J Biol Chem. 1995 Jul 28;270(30):17939-46 [7629100] Genomics. 1995 May 1;27(1):200-3 [7665172] Carcinogenesis. 1996 Aug;17(8):1561-6 [8761410] Eur J Cell Biol. 1996 Jun;70(2):97-105 [8793381] J Biol Chem. 1998 Mar 27;273(13):7668-74 [9516472] Mol Cell Biol. 1998 Apr;18(4):2371-81 [9528806] Mol Cell Biol. 1998 Aug;18(8):4577-88 [9671467] Trends Cell Biol. 1998 Feb;8(2):58-65 [9695810] Nutr Cancer. 1998;31(3):160-7 [9795967] Gene. 1998 Nov 19;222(2):229-35 [9831657] Cell Growth Differ. 1998 Dec;9(12):1015-24 [9869302] Exp Cell Res. 1999 Mar 15;247(2):347-55 [10066362] Biochem Biophys Res Commun. 1999 Mar 24;256(3):614-9 [10080947] EMBO J. 2000 May 2;19(9):1998-2007 [10790366] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Benefits and risks of solitary islet transplantation for type 1 diabetes using steroid-sparing immunosuppression: the National Institutes of Health experience. AN - 71384261; 14633816 AB - The aim of this study was to describe the National Institutes of Health's experience initiating an islet isolation and transplantation center, including descriptions of our first six recipients, and lessons learned. Six females with chronic type 1 diabetes, hypoglycemia unawareness, and no endogenous insulin secretion (undetectable serum C-peptide) were transplanted with allogenic islets procured from brain dead donors. To prevent islet rejection, patients received daclizumab, sirolimus, and tacrolimus. All patients noted less frequent and less severe hypoglycemia, and one-half were insulin independent at 1 year. Serum C-peptide persists in all but one patient (follow-up 17-22 months), indicating continued islet function. Two major procedure-related complications occurred: partial portal vein thrombosis and intra-abdominal hemorrhage. While we observed no cytomegalovirus infection or malignancy, recipients frequently developed transient mouth ulcers, diarrhea, edema, hypercholesterolemia, weight loss, myelosuppression, and other symptoms. Three patients discontinued immunosuppressive therapy: two because of intolerable toxicity (deteriorating kidney function and sirolimus-induced pneumonitis) while having evidence for continued islet function (one was insulin independent) and one because of gradually disappearing islet function. We established an islet isolation and transplantation program and achieved a 50% insulin-independence rate after at most two islet infusions. Our experience demonstrates that centers not previously engaged in islet transplantation can initiate a program, and our data and literature analysis support not only the promise of islet transplantation but also its remaining hurdles, which include the limited islet supply, procedure-associated complications, imperfect immunosuppressive regimens, suboptimal glycemia control, and loss of function over time. JF - Diabetes care AU - Hirshberg, Boaz AU - Rother, Kristina I AU - Digon, Benigno J AU - Lee, Janet AU - Gaglia, Jason L AU - Hines, Kenneth AU - Read, Elizabeth J AU - Chang, Richard AU - Wood, Bradford J AU - Harlan, David M AD - Transplantation and Autoimmunity Branch, National Institutes of Health/Department of Health and Human Services, Bethesda, Maryland, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 3288 EP - 3295 VL - 26 IS - 12 SN - 0149-5992, 0149-5992 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Humanized KW - Blood Glucose KW - Immunoglobulin G KW - Immunosuppressive Agents KW - daclizumab KW - CUJ2MVI71Y KW - Sirolimus KW - W36ZG6FT64 KW - Tacrolimus KW - WM0HAQ4WNM KW - Index Medicus KW - Reproducibility of Results KW - Blood Glucose -- metabolism KW - Humans KW - Hypoglycemia -- epidemiology KW - Drug Therapy, Combination KW - Immunosuppression -- adverse effects KW - Adult KW - Postoperative Complications -- epidemiology KW - Follow-Up Studies KW - Middle Aged KW - Postoperative Complications -- classification KW - Time Factors KW - Immunosuppression -- methods KW - Female KW - Diabetes Mellitus, Type 1 -- immunology KW - Tacrolimus -- therapeutic use KW - Islets of Langerhans Transplantation -- adverse effects KW - Sirolimus -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use KW - Diabetes Mellitus, Type 1 -- surgery KW - Immunoglobulin G -- therapeutic use KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71384261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%2C+USA&rft.atitle=Long-term+correction+of+globotriaosylceramide+storage+in+Fabry+mice+by+recombinant+adeno-associated+virus-mediated+gene+transfer&rft.au=Park%2C+J%3BMurray%2C+G+J%3BLimaye%2C+A%3BQuirk%2C+J+M%3BGelderman%2C+M+P%3BBrady%2C+RO%3BQasba%2C+P&rft.aulast=Park&rft.aufirst=J&rft.date=2003-03-18&rft.volume=100&rft.issue=6&rft.spage=3450&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.0537900100 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-13 N1 - Date created - 2003-11-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Diabetes Care. 2004 May;27(5):1249-50; author reply 1250-1 [15111573] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I and pharmacologic study of weekly gemcitabine in combination with infusional 5-fluorodeoxyuridine and oral calcium leucovorin. AN - 71367818; 12955469 AB - Since preclinical studies have shown more than additive cytotoxicity and DNA damage with the combination of gemcitabine and 5-fluoro-2'-deoxyuridine (FUDR), we studied this combination in a phase I trial. Gemcitabine alone was given in cycle 1 as a 24-h, 2-h or 1-h i.v. infusion weekly for 3 of 4 weeks; if tolerated, a 24-h i.v. infusion of FUDR was added with oral leucovorin. The cycle was aborted for grade 3 thrombocytopenia, grade 4 neutropenia, and grade 2 or worse nonhematologic toxicity. During cycle 1, six of eight patients who received 150 or 100 mg/m2 over 24 h had dose-limiting neutropenia, thrombocytopenia, fatigue or mucositis. Six of seven patients treated with 1000 mg/m2 over 2 h required a gemcitabine dose reduction for cycle 2 (thrombocytopenia, neutropenia, fatigue). Of 25 assessable patients who received gemcitabine 1000 mg/m2 over 1 h, 7 did not complete cycle 1 due to thrombocytopenia (n=6) or diarrhea (n=1). Of 42 patients entered, 27 received at least one course of gemcitabine/FUDR (5-19.5 mg/m2 over 24 h) without appreciable toxicity. Due to a shortage of FUDR, the protocol was closed early. Gemcitabine plasma concentrations averaged 0.061 micro M (24 h), 16.3 micro M (2 h), and 31.9 micro M (1 h). In 21 paired bone marrow mononuclear cell samples obtained before treatment and during FUDR infusion, thymidylate synthase ternary complex was only seen during FUDR infusion. Gemcitabine 100-150 mg/m2 over 24 h was poorly tolerated, whereas toxicity was acceptable with 800-1000 mg/m2 over 1 h. Inhibition of the target enzyme was demonstrated at all FUDR doses. JF - Cancer chemotherapy and pharmacology AU - Grem, Jean L AU - Quinn, Mary G AU - Keith, Bruce AU - Monahan, Brian P AU - Hamilton, J Michael AU - Xu, Yan AU - Harold, Nancy AU - Nguyen, Dat AU - Takimoto, Chris H AU - Rowedder, Anthony AU - Pang, Janet AU - Morrison, Geraldine AU - Chen, Alice AD - National Cancer Institute-Navy Medical Oncology, National Naval Medical Center, Bethesda, MD 20889, USA. gremj@mail.nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 487 EP - 496 VL - 52 IS - 6 SN - 0344-5704, 0344-5704 KW - Floxuridine KW - 039LU44I5M KW - Deoxycytidine KW - 0W860991D6 KW - gemcitabine KW - B76N6SBZ8R KW - Ribonucleotide Reductases KW - EC 1.17.4.- KW - Leucovorin KW - Q573I9DVLP KW - Index Medicus KW - Administration, Oral KW - Drug Administration Schedule KW - Infusions, Intravenous KW - Humans KW - Leucovorin -- administration & dosage KW - Ribonucleotide Reductases -- antagonists & inhibitors KW - Neutropenia -- chemically induced KW - Aged KW - Floxuridine -- administration & dosage KW - Adult KW - Thrombocytopenia -- chemically induced KW - Middle Aged KW - Maximum Tolerated Dose KW - Female KW - Male KW - Neoplasms -- drug therapy KW - Neoplasms -- enzymology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacokinetics KW - Deoxycytidine -- analogs & derivatives KW - Deoxycytidine -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71367818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=A+phase+I+and+pharmacologic+study+of+weekly+gemcitabine+in+combination+with+infusional+5-fluorodeoxyuridine+and+oral+calcium+leucovorin.&rft.au=Grem%2C+Jean+L%3BQuinn%2C+Mary+G%3BKeith%2C+Bruce%3BMonahan%2C+Brian+P%3BHamilton%2C+J+Michael%3BXu%2C+Yan%3BHarold%2C+Nancy%3BNguyen%2C+Dat%3BTakimoto%2C+Chris+H%3BRowedder%2C+Anthony%3BPang%2C+Janet%3BMorrison%2C+Geraldine%3BChen%2C+Alice&rft.aulast=Grem&rft.aufirst=Jean&rft.date=2003-12-01&rft.volume=52&rft.issue=6&rft.spage=487&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-24 N1 - Date created - 2003-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular cloning, characterization, and distribution of the gerbil angiotensin II AT2 receptor. AN - 71366752; 14615403 AB - We isolated a cDNA clone encoding the gerbil AT2 receptor (gAT2) gene from a gerbil adrenal gland cDNA library. The full-length cDNA contains a 1,089-bp open reading frame encoding 363 amino acid residues with 90.9, 96.1, and 95.6% identity with the human (hAT2), rat (rAT2), and mouse AT2 (mAT2) receptors, respectively. There are at least seven nonconserved amino acids in the NH2-terminal domain and in positions Val196, Val217, and Met293, important for angiotensin (ANG) II but not for CGP-42112 binding. Displacement studies in adrenal sections revealed that affinity of the gAT2 receptor was 10-20 times lower for ANG II, ANG III, and PD-123319 than was affinity of the rAT2 receptor. The affinity of each receptor remained the same for CGP-42112. When transfected into COS-7 cells, the gAT2 receptor shows affinity for ANG II that is three times lower than that shown by the hAT2 receptor, whereas affinities for ANG III and the AT2 receptor ligands CGP-42112 and PD-123319 were similar. Autoradiography in sections of the gerbil head showed higher binding in muscles, retina, skin, and molars at embryonic day 19 than at 1 wk of age. In situ hybridization and emulsion autoradiography revealed that at embryonic day 19 the gAT2 receptor mRNA was highly localized to the base of the dental papilla of maxillary and mandibular molars. Our results suggest selective growth-related functions in late gestation and early postnatal periods for the gAT2 receptor and provide an essential basis for future mutagenesis studies to further define structural requirements for agonist binding. JF - American journal of physiology. Regulatory, integrative and comparative physiology AU - Hoe, Kwang-Lae AU - Armando, Ines AU - Baiardi, Gustavo AU - Sreenath, Taduru AU - Kulkarni, Ashok AU - Martínez, Alfredo AU - Saavedra, Juan M AD - Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-1514, USA. armandoi@intra.nimh.nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - R1373 EP - R1383 VL - 285 IS - 6 SN - 0363-6119, 0363-6119 KW - RNA, Messenger KW - 0 KW - Receptor, Angiotensin, Type 2 KW - Index Medicus KW - Animals KW - Gerbillinae KW - Blotting, Northern KW - COS Cells KW - RNA, Messenger -- analysis KW - Amino Acid Sequence KW - Radioligand Assay KW - Protein Binding KW - Cloning, Molecular KW - Rats KW - In Situ Hybridization KW - Transfection KW - Blotting, Southern KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - Species Specificity KW - Gene Expression Regulation, Developmental KW - Male KW - Receptor, Angiotensin, Type 2 -- metabolism KW - Receptor, Angiotensin, Type 2 -- chemistry KW - Adrenal Glands -- embryology KW - Head -- embryology KW - Tooth -- embryology KW - Receptor, Angiotensin, Type 2 -- genetics KW - Adrenal Glands -- physiology KW - Head -- physiology KW - Tooth -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71366752?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+physiology.+Regulatory%2C+integrative+and+comparative+physiology&rft.atitle=Molecular+cloning%2C+characterization%2C+and+distribution+of+the+gerbil+angiotensin+II+AT2+receptor.&rft.au=Hoe%2C+Kwang-Lae%3BArmando%2C+Ines%3BBaiardi%2C+Gustavo%3BSreenath%2C+Taduru%3BKulkarni%2C+Ashok%3BMart%C3%ADnez%2C+Alfredo%3BSaavedra%2C+Juan+M&rft.aulast=Hoe&rft.aufirst=Kwang-Lae&rft.date=2003-12-01&rft.volume=285&rft.issue=6&rft.spage=R1373&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Regulatory%2C+integrative+and+comparative+physiology&rft.issn=03636119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-07 N1 - Date created - 2003-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strand-specific RNA synthesis defects in a poliovirus with a mutation in protein 3A. AN - 71364351; 14610190 AB - Substitution of a methionine residue at position 79 in poliovirus protein 3A with valine or threonine caused defective viral RNA synthesis, manifested as delayed onset and reduced yield of viral RNA, in HeLa cells transfected with a luciferase-containing replicon. Viruses containing these same mutations produced small or minute plaques that generated revertants upon further passage, with either wild-type 3A sequences or additional nearby compensating mutations. Translation and polyprotein processing were not affected by the mutations, and 3AB proteins containing the altered amino acids at position 79 showed no detectable loss of membrane-binding activity. Analysis of individual steps of viral RNA synthesis in HeLa cell extracts that support translation and replication of viral RNA showed that VPg uridylylation and negative-strand RNA synthesis occurred normally from mutant viral RNA; however, positive-strand RNA synthesis was specifically reduced. The data suggest that a function of viral protein 3A is required for positive-strand RNA synthesis but not for production of negative strands. JF - Journal of virology AU - Teterina, Natalya L AU - Rinaudo, Mario S AU - Ehrenfeld, Ellie AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 12679 EP - 12691 VL - 77 IS - 23 SN - 0022-538X, 0022-538X KW - 3A protein, Poliovirus KW - 0 KW - RNA, Viral KW - Viral Core Proteins KW - Index Medicus KW - Virus Replication KW - Defective Viruses -- genetics KW - Base Sequence KW - HeLa Cells KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Defective Viruses -- physiology KW - Mutagenesis KW - Poliovirus -- physiology KW - RNA, Viral -- biosynthesis KW - RNA, Viral -- chemistry KW - Viral Core Proteins -- genetics KW - Poliovirus -- genetics KW - RNA, Viral -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71364351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Strand-specific+RNA+synthesis+defects+in+a+poliovirus+with+a+mutation+in+protein+3A.&rft.au=Teterina%2C+Natalya+L%3BRinaudo%2C+Mario+S%3BEhrenfeld%2C+Ellie&rft.aulast=Teterina&rft.aufirst=Natalya&rft.date=2003-12-01&rft.volume=77&rft.issue=23&rft.spage=12679&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - 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Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of nitric oxide on cytotoxicity of Taxol: enhanced Taxol transcellular permeability. AN - 71361260; 14609744 AB - The present studies were aimed at testing the hypothesis that nitric oxide (NO) may enhance Taxol-induced cytotoxicity in carcinoma cells by increasing influx of Taxol into intracellular compartments. Prostate carcinoma cells (PC-3, LNCaP) and neuroblastoma cells (SKNDZ, CHP212) were used to investigate both transmembrane permeability and cytotoxicity of Taxol in the presence and absence of S-nitrosocaptopril (CapNO), a nitric oxide donating compound. The order of permeability rate of Taxol across the four cell lines was SKNDZ>LNCaP>PC-3>CHP212. Pretreatment of the cell lines with CapNO (100 microM) enhanced permeability of Taxol across prostate PC-3 and LNCaP cells, but not neuroblastoma SKNDZ and CHP212 cells. Taxol inhibited cell growth at nanomolar levels with IC(50)s of 0.21, 17.4, 96.4 and 842.9 nM corresponding to SKNDZ, PC-3, LNCaP and CHP212 cells, respectively. However, CapNO inhibited proliferation of the four cell lines at millimolar levels with IC(50)s ranging from 0.3 to 1.1 mM. Enhancing effect of CapNO (100 microM) on Taxol cytotoxicity were found in PC-3 and LNCaP cells, but not in SKNDZ and CHP212. The findings suggest that the cytotoxic potency of Taxol is mainly dependent upon the cell membrane permeabilization to Taxol, and the enhancing effect of CapNO on Taxol-induced cytotoxicity is primarily mediated via the increased influx of Taxol by NO into intracellular compartments, while NO-induced cytotoxicity cannot be excluded. JF - Biochemical pharmacology AU - Jia, Lee AU - Schweizer, Julia AU - Wang, Yao AU - Cerna, Cesario AU - Wong, Hong AU - Revilla, Marcus AD - Cancer Therapy & Research Center, Institute for Drug Development, 14960 Omicron Dr., San Antonio, TX 78245-3217, USA. Jiale@mail.nih.gov Y1 - 2003/12/01/ PY - 2003 DA - 2003 Dec 01 SP - 2193 EP - 2199 VL - 66 IS - 11 SN - 0006-2952, 0006-2952 KW - Nitric Oxide Donors KW - 0 KW - Nitric Oxide KW - 31C4KY9ESH KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Nitric Oxide Donors -- pharmacology KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Line, Tumor KW - Biological Transport -- physiology KW - Biological Transport -- drug effects KW - Paclitaxel -- toxicity KW - Cell Membrane Permeability -- physiology KW - Cell Membrane Permeability -- drug effects KW - Paclitaxel -- pharmacokinetics KW - Nitric Oxide -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71361260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+nitric+oxide+on+cytotoxicity+of+Taxol%3A+enhanced+Taxol+transcellular+permeability.&rft.au=Jia%2C+Lee%3BSchweizer%2C+Julia%3BWang%2C+Yao%3BCerna%2C+Cesario%3BWong%2C+Hong%3BRevilla%2C+Marcus&rft.aulast=Jia&rft.aufirst=Lee&rft.date=2003-12-01&rft.volume=66&rft.issue=11&rft.spage=2193&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 - 2004-01-05 N1 - Date created - 2003-11-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Central role for the Werner syndrome protein/poly(ADP-ribose) polymerase 1 complex in the poly(ADP-ribosyl)ation pathway after DNA damage. AN - 71355826; 14612404 AB - A defect in the Werner syndrome protein (WRN) leads to the premature aging disease Werner syndrome (WS). Hallmark features of cells derived from WS patients include genomic instability and hypersensitivity to certain DNA-damaging agents. WRN contains a highly conserved region, the RecQ conserved domain, that plays a central role in protein interactions. We searched for proteins that bound to this region, and the most prominent direct interaction was with poly(ADP-ribose) polymerase 1 (PARP-1), a nuclear enzyme that protects the genome by responding to DNA damage and facilitating DNA repair. In pursuit of a functional interaction between WRN and PARP-1, we found that WS cells are deficient in the poly(ADP-ribosyl)ation pathway after they are treated with the DNA-damaging agents H2O2 and methyl methanesulfonate. After cellular stress, PARP-1 itself becomes activated, but the poly(ADP-ribosyl)ation of other cellular proteins is severely impaired in WS cells. Overexpression of the PARP-1 binding domain of WRN strongly inhibits the poly(ADP-ribosyl)ation activity in H2O2-treated control cell lines. These results indicate that the WRN/PARP-1 complex plays a key role in the cellular response to oxidative stress and alkylating agents, suggesting a role for these proteins in the base excision DNA repair pathway. JF - Molecular and cellular biology AU - von Kobbe, Cayetano AU - Harrigan, Jeanine A AU - May, Alfred AU - Opresko, Patricia L AU - Dawut, Lale AU - Cheng, Wen-Hsing AU - Bohr, Vilhelm A AD - Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 8601 EP - 8613 VL - 23 IS - 23 SN - 0270-7306, 0270-7306 KW - Luminescent Proteins KW - 0 KW - Macromolecular Substances KW - Recombinant Fusion Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Poly Adenosine Diphosphate Ribose KW - 26656-46-2 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Hydrogen Peroxide KW - BBX060AN9V KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Exodeoxyribonucleases KW - EC 3.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - WRN protein, human KW - Werner Syndrome Helicase KW - Index Medicus KW - DNA Repair KW - HeLa Cells KW - Humans KW - Luminescent Proteins -- metabolism KW - Recombinant Fusion Proteins -- chemistry KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Hydrogen Peroxide -- toxicity KW - Methyl Methanesulfonate -- toxicity KW - Oxidative Stress KW - Recombinant Fusion Proteins -- genetics KW - Protein Structure, Tertiary KW - Mutation KW - Luminescent Proteins -- genetics KW - Cell Line KW - DNA Helicases -- chemistry KW - Werner Syndrome -- metabolism KW - DNA Helicases -- metabolism KW - Poly(ADP-ribose) Polymerases -- chemistry KW - DNA Damage KW - DNA Helicases -- genetics KW - Werner Syndrome -- genetics KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Poly Adenosine Diphosphate Ribose -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71355826?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Central+role+for+the+Werner+syndrome+protein%2Fpoly%28ADP-ribose%29+polymerase+1+complex+in+the+poly%28ADP-ribosyl%29ation+pathway+after+DNA+damage.&rft.au=von+Kobbe%2C+Cayetano%3BHarrigan%2C+Jeanine+A%3BMay%2C+Alfred%3BOpresko%2C+Patricia+L%3BDawut%2C+Lale%3BCheng%2C+Wen-Hsing%3BBohr%2C+Vilhelm+A&rft.aulast=von+Kobbe&rft.aufirst=Cayetano&rft.date=2003-12-01&rft.volume=23&rft.issue=23&rft.spage=8601&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 - 2003-12-16 N1 - Date created - 2003-11-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Exp Cell Res. 1992 Oct;202(2):267-73 [1327851] Science. 1992 Aug 28;257(5074):1220-4 [1355616] Mutat Res. 1994 Feb;316(1):37-48 [7507567] Dermatol Clin. 1995 Jan;13(1):163-8 [7712642] Science. 1996 Apr 12;272(5259):258-62 [8602509] Mutat Res. 1996 Aug 17;355(1-2):71-89 [8781578] Exp Cell Res. 1996 Aug 25;227(1):146-53 [8806461] J Biol Chem. 1998 May 8;273(19):11839-43 [9565608] J Mol Med (Berl). 1998 Apr;76(5):346-54 [9587069] Mol Cell Biol. 1998 Jun;18(6):3563-71 [9584196] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6887-92 [9618508] Hum Genet. 1999 Jan;104(1):10-4 [10071186] Genes Dev. 1999 Jun 1;13(11):1355-60 [10364153] J Biol Chem. 1999 Jun 25;274(26):18341-50 [10373438] J Biol Chem. 1999 Jul 16;274(29):20521-8 [10400681] Nucleic Acids Res. 1999 Sep 1;27(17):3557-66 [10446247] J Biol Chem. 1999 Nov 5;274(45):32122-6 [10542247] J Biol Chem. 1999 Dec 31;274(53):37795-9 [10608841] Ann N Y Acad Sci. 1999;887:133-49 [10668470] Carcinogenesis. 2000 Mar;21(3):361-70 [10688856] Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4603-8 [10781066] Biochemistry. 2000 Jun 27;39(25):7559-69 [10858306] Nucleic Acids Res. 2000 Jul 15;28(14):2762-70 [10908333] Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11365-70 [11027336] J Immunol Methods. 2000 Oct 20;244(1-2):145-51 [11033027] Exp Gerontol. 2000 Sep;35(6-7):695-702 [11053659] J Biol Chem. 2000 Dec 29;275(52):40974-80 [11016934] Bioessays. 2001 Jun;23(6):543-8 [11385634] Mol Biol Cell. 2001 Aug;12(8):2412-21 [11514625] J Biol Chem. 2001 Aug 31;276(35):32411-4 [11440997] EMBO J. 2001 Oct 15;20(20):5791-801 [11598021] Biochim Biophys Acta. 2001 Nov 30;1552(1):27-37 [11781113] Chembiochem. 2001 Oct 1;2(10):725-8 [11948853] FASEB J. 2002 May;16(7):757-8 [11978740] Free Radic Biol Med. 2002 May 1;32(9):804-12 [11978482] J Biol Chem. 2002 Jun 14;277(24):22035-44 [11919194] Ageing Res Rev. 2002 Jun;1(3):397-411 [12067594] J Biol Chem. 2002 Jun 21;277(25):23028-36 [11948190] J Cell Sci. 2002 Oct 15;115(Pt 20):3901-7 [12244128] Mutat Res. 2000 Nov 30;456(1-2):45-57 [11087895] J Biol Chem. 2002 Oct 25;277(43):41110-9 [12181313] DNA Repair (Amst). 2002 Mar 28;1(3):175-207 [12509252] Am J Pathol. 2003 May;162(5):1559-69 [12707040] J Biol Chem. 2003 Jun 20;278(25):22686-95 [12665521] Birth Defects Orig Artic Ser. 1978;14(1):5-39 [147113] J Gerontol. 1981 Jul;36(4):405-9 [7252070] Exp Eye Res. 1981 Dec;33(6):673-81 [7318962] Exp Gerontol. 1982;17(6):473-80 [7183454] Mech Ageing Dev. 1983 Feb;21(2):157-67 [6223188] Gene. 1992 May 15;114(2):279-83 [1601310] Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11759-63 [1465394] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tracking gene expression in primary immunodeficiencies. AN - 71349854; 14612667 AB - Extensive research on molecular genetics in recent decades has provided a wealth of information about the mechanisms of primary immunodeficiency diseases. Microarray technology enables the survey of the expression of thousands of genes simultaneously. This review focuses on the commonly used arrays and initial applications in the study of primary immunodeficiency diseases. The application of this technology has been found to accelerate the discovery rate of gene expression disturbances in primary immunodeficiency diseases and provide potential molecular diagnostic tools. The important role of microarray technology in functional genomic study has been demonstrated by the exponential growth in the number of scientific publications in the last few years. Microarray analysis has been used to study gene expression in several immunodeficiency diseases with known gene mutations as well as those with unknown causes. It has provided snapshots of gene expression and has presented the molecular phenotypes in the cells at defined times and under certain stimulation conditions. Studies comparing differential gene expression in patients and normal controls have allowed us to better understand the immunodeficiencies at the molecular level. Application of microarray technology in immunodeficiency study has facilitated tracking the expression of thousands of genes simultaneously. The molecular phenotypes obtained from microarray results can be used in diagnosis of diseases, supplemental to clinical phenotypes. It is a powerful survey tool that can detect disturbed gene expression in immunodeficiency diseases, which will provide clues for disease gene discovery and potential targets for drug development. JF - Current opinion in allergy and clinical immunology AU - Qin, Haiying AU - Yamada, Masafumi AU - Tian, Lan AU - Stewart, Donn M AU - Gulino, A Virginia AU - Nelson, David L AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 437 EP - 442 VL - 3 IS - 6 SN - 1528-4050, 1528-4050 KW - AM336 KW - 0 KW - RNA, Messenger KW - Venoms KW - omega-Conotoxins KW - Methyltransferases KW - EC 2.1.1.- KW - Index Medicus KW - Methyltransferases -- genetics KW - T-Lymphocytes -- metabolism KW - RNA, Messenger -- metabolism KW - IgA Deficiency -- genetics KW - Humans KW - Venoms -- genetics KW - B-Lymphocytes -- metabolism KW - RNA, Messenger -- genetics KW - B-Lymphocytes -- enzymology KW - T-Lymphocytes -- enzymology KW - Severe Combined Immunodeficiency -- genetics KW - Gene Expression -- genetics KW - Oligonucleotide Array Sequence Analysis -- methods KW - Immunologic Deficiency Syndromes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71349854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+allergy+and+clinical+immunology&rft.atitle=Tracking+gene+expression+in+primary+immunodeficiencies.&rft.au=Qin%2C+Haiying%3BYamada%2C+Masafumi%3BTian%2C+Lan%3BStewart%2C+Donn+M%3BGulino%2C+A+Virginia%3BNelson%2C+David+L&rft.aulast=Qin&rft.aufirst=Haiying&rft.date=2003-12-01&rft.volume=3&rft.issue=6&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+allergy+and+clinical+immunology&rft.issn=15284050&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-12 N1 - Date created - 2003-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of CXCR4 expression in human T lymphocytes by calcium and calcineurin. AN - 71288852; 14563373 AB - Principally expressed on the surface of T lymphocytes, the chemokine and HIV receptor CXCR4 has been shown to serve key roles in both chemotaxis and HIV-1-entry into T cells. Understanding the regulation of CXCR4 expression is therefore of paramount importance to further elucidating its endogenous role and contributions to HIV-1 pathogenesis. Using an RNase protection assay (RPA), we have demonstrated that mitogenic stimulation of purified human peripheral blood T lymphocytes (PBL) decreased CXCR4 mRNA relative to unstimulated controls in a calcineurin-dependent manner; an expression pattern mimicked by the chemokine receptor CCR7. A change in transcriptional activity, not in mRNA stability, was required for control of CXCR4 and CCR7 expression. Changes in CXCR4 mRNA expression translated into a stimulation- and calcineurin-dependent decrease in cell surface CXCR4 expression. We have previously demonstrated that CXCR4 mRNA and protein is regulated by cAMP; here we show that calcium and calcineurin signaling pathways modify cAMP-driven changes. Moreover, we provide data supporting a role for the transcription factor YY1 in calcineurin-dependent regulation of CXCR4 expression. JF - Molecular immunology AU - Cristillo, Anthony D AU - Bierer, Barbara E AD - Laboratory of Lymphocyte Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 539 EP - 553 VL - 40 IS - 8 SN - 0161-5890, 0161-5890 KW - Receptors, CXCR4 KW - 0 KW - Dactinomycin KW - 1CC1JFE158 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcineurin KW - EC 3.1.3.16 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Tetradecanoylphorbol Acetate -- metabolism KW - Promoter Regions, Genetic KW - Dactinomycin -- metabolism KW - Humans KW - Calcium -- metabolism KW - T-Lymphocytes -- metabolism KW - Calcineurin -- metabolism KW - Receptors, CXCR4 -- biosynthesis KW - Gene Expression Regulation KW - Receptors, CXCR4 -- genetics KW - T-Lymphocytes -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71288852?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+immunology&rft.atitle=Regulation+of+CXCR4+expression+in+human+T+lymphocytes+by+calcium+and+calcineurin.&rft.au=Cristillo%2C+Anthony+D%3BBierer%2C+Barbara+E&rft.aulast=Cristillo&rft.aufirst=Anthony&rft.date=2003-12-01&rft.volume=40&rft.issue=8&rft.spage=539&rft.isbn=&rft.btitle=&rft.title=Molecular+immunology&rft.issn=01615890&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-09 N1 - Date created - 2003-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Does Stage at Diagnosis Influence the Observed Relationship between Socioeconomic Status and Breast Cancer Incidence, Case-Fatality and Mortality? AN - 60484620; 200409542 AB - Historically, lower socioeconomic status (SES) has been reported to be associated with decreased breast cancer incidence & mortality & increased case-fatality, although recent trends in breast cancer screening & treatment may alter these relationships. This study assessed the associations between SES & breast cancer incidence, case-fatality, & mortality by stage of disease at diagnosis using recent data in the US. Breast cancer incidence & survival data from the Surveillance, Epidemiology, & End Results (SEER) tumor registry for black & white women aged 55 & above were linked to county-level SES & population data based on place of residence. Poisson regression was used to calculate age-adjusted relative rates associated with SES levels & breast cancer incidence, case-fatality, & mortality. As SES decreased, localized breast cancer incidence rates decreased, while incidence rates of distant disease increased. Five-year localized & regional breast cancer case-fatality rates increased as SES decreased. Localized breast cancer mortality rates decreased as SES declined, whereas regional breast cancer mortality rates tended to increase. These results confirm some previously reported findings & suggest that associations between lower SES & lower localized breast cancer mortality rates are influenced mainly by underlying associations between SES & localized breast cancer incidence, whereas regional breast cancer mortality rates appear to reflect the underlying association between SES & regional case-fatality rates. 6 Tables, 1 Figure, 78 References. Adapted from the source document. JF - Social Science & Medicine AU - Yabroff, K Robin AU - Gordis, Leon AD - Applied Research Program, Division Cancer Control & Population Sciences, National Cancer Instit, Bethesda, MD e-mail:yabroffr@mail.nih.gov Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 2265 EP - 2279 VL - 57 IS - 12 SN - 0277-9536, 0277-9536 KW - Whites KW - Black Americans KW - Mortality Rates KW - Socioeconomic Status KW - Elderly KW - Breast Cancer KW - United States of America KW - Females KW - Middle Aged Adults KW - article KW - 2045: sociology of health and medicine; sociology of medicine & health care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60484620?accountid=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=Social+Science+%26+Medicine&rft.atitle=Does+Stage+at+Diagnosis+Influence+the+Observed+Relationship+between+Socioeconomic+Status+and+Breast+Cancer+Incidence%2C+Case-Fatality+and+Mortality%3F&rft.au=Yabroff%2C+K+Robin%3BGordis%2C+Leon&rft.aulast=Yabroff&rft.aufirst=K&rft.date=2003-12-01&rft.volume=57&rft.issue=12&rft.spage=2265&rft.isbn=&rft.btitle=&rft.title=Social+Science+%26+Medicine&rft.issn=02779536&rft_id=info:doi/10.1016%2FS0277-9536%2803%2900100-X LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Number of references - 78 N1 - Last updated - 2016-09-28 N1 - CODEN - SSCMAW N1 - SubjectsTermNotLitGenreText - Mortality Rates; Breast Cancer; Socioeconomic Status; Middle Aged Adults; Females; Elderly; Black Americans; Whites; United States of America DO - http://dx.doi.org/10.1016/S0277-9536(03)00100-X ER - TY - JOUR T1 - Toxicity of glucosylsphingosine (glucopsychosine) to cultured neuronal cells: a model system for assessing neuronal damage in Gaucher disease type 2 and 3 AN - 20538366; 8068362 AB - Patients with Gaucher disease have been classified as type 1 nonneuronopathic, type 2 acute neuronopathic, and type 3 chronic neuronopathic phenotypes. Increased quantities of glucocerebroside and glucosylsphingosine (glucopsychosine) are present in the brain of type 2 and type 3 Gaucher patients. Galactosylsphingosine has previously been shown to be neurotoxic in globoid cell leukodystrophy (Krabbe disease). To determine whether glucosylsphingosine is also neurotoxic, we examined its effect on cultured cholinergic neuron-like LA-N-2 cells. When these cells were exposed to 1, 5, or 10 is a subset of M glucosylsphingosine for a period of 18 h, they became shriveled, neurite outgrowth was suppressed, and the activities of the lysosomal enzymes glucocerebrosidase, sphingomyelinase, and beta -galactosidase were reduced in a dose-dependent manner. Acetylcholine in cells exposed to glucosylsphingosine also declined. Cells switched to glucosylsphingosine-free medium partially recovered. The data suggest that accumulation of glucosylsphingosine contributes to neuronal dysfunction and destruction in patients with neuronopathic Gaucher disease. JF - Neurobiology of Disease AU - Schueler, U H AU - Kolter, T AU - Kaneski, C R AU - Blusztajn, J K AU - Herkenham, M AU - Sandhoff, K AU - Brady, R O AD - Developmental and Metabolic Neurology Branch, NINDS, NIH, DHHS, Bethesda, MD, USA, SchueleU@ninds.nih.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 595 EP - 601 PB - Elsevier Science, The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 14 IS - 3 SN - 0969-9961, 0969-9961 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Neuronopathic Gaucher disease KW - Glucosylsphingosine KW - Glucopsychosine KW - Acetylcholine KW - Cholinergic LA-N-2 cells KW - Data processing KW - beta -Galactosidase KW - Brain KW - Toxicity KW - Lysosomal enzymes KW - Glucosylceramidase KW - Leukodystrophy KW - Nervous system KW - Neurotoxicity KW - Gaucher's disease KW - Axonogenesis KW - Sphingomyelin phosphodiesterase KW - X 24310:Pharmaceuticals KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20538366?accountid=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=Neurobiology+of+Disease&rft.atitle=Toxicity+of+glucosylsphingosine+%28glucopsychosine%29+to+cultured+neuronal+cells%3A+a+model+system+for+assessing+neuronal+damage+in+Gaucher+disease+type+2+and+3&rft.au=Schueler%2C+U+H%3BKolter%2C+T%3BKaneski%2C+C+R%3BBlusztajn%2C+J+K%3BHerkenham%2C+M%3BSandhoff%2C+K%3BBrady%2C+R+O&rft.aulast=Schueler&rft.aufirst=U&rft.date=2003-12-01&rft.volume=14&rft.issue=3&rft.spage=595&rft.isbn=&rft.btitle=&rft.title=Neurobiology+of+Disease&rft.issn=09699961&rft_id=info:doi/10.1016%2Fj.nbd.2003.08.016 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-04-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Data processing; beta -Galactosidase; Brain; Toxicity; Glucosylceramidase; Lysosomal enzymes; Leukodystrophy; Nervous system; Gaucher's disease; Neurotoxicity; Axonogenesis; Acetylcholine; Sphingomyelin phosphodiesterase DO - http://dx.doi.org/10.1016/j.nbd.2003.08.016 ER - TY - JOUR T1 - Broadly cross-reactive HIV neutralizing human monoclonal antibody Fab selected by sequential antigen panning of a phage display library AN - 19259030; 5848913 AB - Identification of broadly cross-reactive human monoclonal antibodies (mAbs) has major implications for development of vaccines, inhibitors and research tools. Here we describe a sequential antigen panning (SAP) methodology that may facilitate the selection of such antibodies. An HIV-specific antibody Fab (m18) was selected from a human Fab phage-display library by SAP against several recombinant soluble HIV envelope glycoproteins (Envs) and Env-sCD4 complexes. This Fab bound to a variety of recombinant soluble Envs (gp140s) from primary HIV isolates representing different clades, and inhibited cell fusion and virus entry mediated by Envs of primary HIV isolates. The methodology and the results may have implications for development of HIV vaccines and inhibitors, as well as for identification of antibodies to conserved epitopes on rapidly mutating viruses and cells. JF - Journal of Immunological Methods AU - Zhang, M AU - Shu, Y AU - Phogat, S AU - Xiao, X AU - Cham, F AU - Bouma, P AU - Choudhary, A AU - Feng, Y AU - Sanz, I AU - Rybak, S AU - Broder, C C AU - Quinnan, GV Jr AU - Evans, T AU - Dimitrov, D S AD - Human Immunovirology Group, Laboratory of Experimental and Computational Biology, CCR, NCI-Frederick, NIH, Bldg 469, Rm 246, P.O. Box B, Miller Drive, Frederick, MD 21702-1201, USA, dimitrov@ncifcrf.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 17 EP - 25 VL - 283 IS - 1-2 SN - 0022-1759, 0022-1759 KW - man KW - HIV KW - Env protein KW - Fab KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Monoclonal antibodies KW - Phage display KW - Antibodies KW - Human immunodeficiency virus KW - W3 33375:Antibodies KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19259030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Broadly+cross-reactive+HIV+neutralizing+human+monoclonal+antibody+Fab+selected+by+sequential+antigen+panning+of+a+phage+display+library&rft.au=Zhang%2C+M%3BShu%2C+Y%3BPhogat%2C+S%3BXiao%2C+X%3BCham%2C+F%3BBouma%2C+P%3BChoudhary%2C+A%3BFeng%2C+Y%3BSanz%2C+I%3BRybak%2C+S%3BBroder%2C+C+C%3BQuinnan%2C+GV+Jr%3BEvans%2C+T%3BDimitrov%2C+D+S&rft.aulast=Zhang&rft.aufirst=M&rft.date=2003-12-01&rft.volume=283&rft.issue=1-2&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/10.1016%2Fj.jim.2003.07.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Monoclonal antibodies; Phage display; Acquired immune deficiency syndrome; Antibodies DO - http://dx.doi.org/10.1016/j.jim.2003.07.003 ER - TY - JOUR T1 - Differential metabolism of acrylonitrile to cyanide is responsible for the greater sensitivity of male vs female mice: role of CYP2E1 and epoxide hydrolases AN - 19254962; 5849150 AB - Acrylonitrile (AN) is a potent toxicant and a known rodent carcinogen. AN epoxidation to cyanoethylene oxide (CEO) via CYP2E1 and its subsequent metabolism via epoxide hydrolases (EH) to yield cyanide is thought to be responsible for the acute toxicity and mortality of AN. Recent reports showed that male mice are more sensitive than females to the acute toxicity/mortality of AN. The present work was undertaken to assess the metabolic and enzymatic basis for the greater sensitivity of male vs female mice to AN toxicity. Male and female wild-type and CYP2E1-null mice received AN at 0, 2.5, 10, 20, or 40 mg/kg by gavage. Cyanide concentrations were measured at 1 or 3 h after dosing. Current data demonstrated that cyanide levels in blood and tissues of AN-treated wild-type mice of both sexes were significantly greater than in vehicle-treated controls and increased in a dose-dependent manner. In contrast, cyanide levels in AN-treated CYP2E1-null mice were not statistically different from those measured in vehicle-treated controls. Furthermore, higher levels of cyanide were detected in male wild-type mice vs females in association with greater sensitivity of males to the acute toxicity/mortality of this chemical. Using Western blot analysis, negligible difference in CYP2E1 expression with higher levels of soluble and microsomal EH (sEH and mEH) was detected in the liver of male vs female mice. In kidneys, male mice exhibited higher expression of both renal CYP2E1 and sEH than did female mice. In conclusion, higher blood and tissue cyanide levels are responsible for the greater sensitivity of male vs female mice to AN. Further, higher expression of CYP2E1 and EH in male mice may contribute to greater formation of CEO and its subsequent metabolism to yield cyanide, respectively. JF - Toxicology and Applied Pharmacology AU - Chanas, B AU - Wang, H AU - Ghanayem, B I AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA, ghanayem@niehs.nih.gov Y1 - 2003/12/01/ PY - 2003 DA - 2003 Dec 01 SP - 293 EP - 302 PB - Elsevier Inc. VL - 193 IS - 2 SN - 0041-008X, 0041-008X KW - mice KW - metabolism KW - Toxicology Abstracts KW - Cyanide KW - Cytochrome P450 KW - Sex differences KW - Epoxide hydrolase KW - Acrylonitrile KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19254962?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Differential+metabolism+of+acrylonitrile+to+cyanide+is+responsible+for+the+greater+sensitivity+of+male+vs+female+mice%3A+role+of+CYP2E1+and+epoxide+hydrolases&rft.au=Chanas%2C+B%3BWang%2C+H%3BGhanayem%2C+B+I&rft.aulast=Chanas&rft.aufirst=B&rft.date=2003-12-01&rft.volume=193&rft.issue=2&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1016%2Fj.taap.2003.08.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Acrylonitrile; Cyanide; Sex differences; Cytochrome P450; Epoxide hydrolase DO - http://dx.doi.org/10.1016/j.taap.2003.08.006 ER - TY - JOUR T1 - Fitness as a Determinant of the Oxygen Uptake/Work Rate Slope in Healthy Children and Children With Inflammatory Myopathy AN - 19232399; 5813001 AB - There is evidence that the slope of the change in oxygen uptake accompanying changes in work rate ( Delta VO sub(2)/ Delta W) during moderate incremental exercise is influenced by fitness (peak VO sub(2)). We set out to determine whether Delta VO sub(2)/ Delta W was related to fitness in a group of healthy children and in children with juvenile dermatomyositis (JDM), a condition associated with decreased peak VO sub(2). We also hypothesized that Delta VO sub(2)/ Delta W would be significantly decreased in children with JDM compared to healthy children. Twelve children (2 boys) with JDM, mean age 11.6 plus or minus 3.6 yrs, and 20 healthy children (4 boys), mean age 11.3 plus or minus 2.9 years, performed an incremental exercise test using a cycle ergometer. Delta VO sub(2)/ Delta W below the anaerobic threshold was analyzed using linear regression. Correlations between peak VO sub(2) and Delta VO sub(2)/ Delta W were calculated, and differences between the JDM and healthy groups were analyzed using independent t-tests. The Delta VO sub(2)/ Delta W was significantly correlated with peakVO sub(2) for children with JDM (r = 0.71, p < 0.01), healthy children (r = 0.53, p < 0.01), and all children combined (r = 0.78, p < 0.001). The Delta VO sub(2)/ Delta W (7.4 plus or minus 1.4 vs. 10.8 plus or minus 1.2 ml O sub(2) times min super(-1) times watt super(-1)) and peak oxygen uptake (VO sub(2)peak) (19.2 plus or minus 5.0 vs. 31.4 plus or minus 7.2 ml O sub(2) times kg super(-1) times min super(-1)) were significantly lower in children with JDM than in healthy children, respectively (all p less than or equal to 0.001). Fitness is significantly related to Delta VO sub(2)/ Delta W in healthy children and those with JDM. Children with JDM have a significantly lower Delta VO sub(2)/ Delta W than healthy children. Further study is needed to identify specific factors influencing Delta VO sub(2)/ Delta W. JF - Canadian Journal of Applied Physiology/Revue Canadienne de Physiologie Appliquee AU - Drinkard, B E AU - Hicks, J AU - Danoff, J AU - Rider, L G AD - Dept. of Rehabilitation Medicine, National Institutes of Environmental Health Sciences, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892-1604, USA Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 888 EP - 897 VL - 28 IS - 6 SN - 1066-7814, 1066-7814 KW - Physical Education Index KW - Bicycling KW - Oxygen consumption KW - Fitness KW - Ergometry KW - Tests KW - Work KW - Health KW - Exercise KW - Children KW - Anaerobics KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19232399?accountid=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=Bioorganic+%26+medicinal+chemistry+letters&rft.atitle=Structure-based+design+of+thioether-bridged+cyclic+phosphopeptides+binding+to+Grb2-SH2+domain.&rft.au=Li%2C+Peng%3BPeach%2C+Megan+L%3BZhang%2C+Manchao%3BLiu%2C+Hongpeng%3BYang%2C+Dajun%3BNicklaus%2C+Marc%3BRoller%2C+Peter+P&rft.aulast=Li&rft.aufirst=Peng&rft.date=2003-03-10&rft.volume=13&rft.issue=5&rft.spage=895&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry+letters&rft.issn=0960894X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Fitness; Oxygen consumption; Work; Health; Children; Exercise; Tests; Bicycling; Ergometry; Anaerobics ER - TY - JOUR T1 - Suppression of Factor-Dependent Transcription Termination by Antiterminator RNA AN - 19229038; 5777532 AB - Nascent transcripts of the phage HK022 put sites modify the transcription elongation complex so that it terminates less efficiently at intrinsic transcription terminators and accelerates through pause sites. We show here that the modification also suppresses termination in vivo at two factor-dependent terminators, one that depends on the bacterial Rho protein and a second that depends on the HK022-encoded Nun protein. Suppression was efficient when the termination factors were present at physiological levels, but an increase in the intracellular concentration of Nun increased termination both in the presence and absence of put. put-mediated antitermination thus shows no apparent terminator specificity, suggesting that put inhibits a step that is common to termination at the different types of terminator. JF - Journal of Bacteriology AU - King, R A AU - Weisberg, R A AD - National Institute of Child Health and Human Development, NIH, Bldg. 6B, Room 3B308, Bethesda, MD 20892-2785, rweisberg@nih.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 7085 EP - 7091 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 185 IS - 24 SN - 0021-9193, 0021-9193 KW - Antiterminator RNA KW - Nun protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts KW - Transcription termination KW - Transcription elongation KW - Rho protein KW - Phage HK022 KW - J 02726:RNA and ribosomes KW - V 22070:Phage-host interactions including lysogeny & transduction KW - N 14553:Transcription initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19229038?accountid=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=Suppression+of+Factor-Dependent+Transcription+Termination+by+Antiterminator+RNA&rft.au=King%2C+R+A%3BWeisberg%2C+R+A&rft.aulast=King&rft.aufirst=R&rft.date=2003-12-01&rft.volume=185&rft.issue=24&rft.spage=7085&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.185.24.7085-7091.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Phage HK022; Transcription termination; Rho protein; Transcription elongation DO - http://dx.doi.org/10.1128/JB.185.24.7085-7091.2003 ER - TY - JOUR T1 - Structural analysis by X-ray crystallography and calorimetry of a haemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum AN - 19228552; 5807713 AB - Botulism food poisoning is caused primarily by ingestion of the Clostridium botulinum neurotoxin (BoNT). The 1300 amino acid BoNT forms a progenitor toxin (PTX) that, when associated with a number of other proteins, increases its oral toxicity by protecting it from the low pH of the stomach and from intestinal proteases. One of these associated proteins, HA1, has also been suggested to be involved with internalization of the toxin into the bloodstream by binding to oligosaccharides lining the intestine. Here is reported the crystal structure of HA1 from type C Clostridium botulinum at a resolution of 1.7 Ae. The protein consists of two beta -trefoil domains and bears structural similarities to the lectin B-chain from the deadly plant toxin ricin. Based on structural comparison to the ricin B-chain lactose-binding sites, residues of type A HA1 were selected and mutated. The D263A and N285A mutants lost the ability to bind carbohydrates containing galactose moieties, implicating these residues in carbohydrate binding. JF - Microbiology AU - Inoue, Kaoru AU - Sobhany, M AU - Transue, T R AU - Oguma, Keiji AU - Pedersen, L C AU - Negishi, Masahiko AD - Pharmacogenetic Section Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA, pederse2@niehs.nih.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 3361 EP - 3370 VL - 149 IS - 12 SN - 1350-0872, 1350-0872 KW - HA1 protein KW - Microbiology Abstracts B: Bacteriology KW - X-ray crystallography KW - Botulism KW - Hemagglutinins KW - Crystal structure KW - Calorimetry KW - Clostridium botulinum KW - Neurotoxins KW - J 02822:Biosynthesis and physicochemical properties UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19228552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbiology&rft.atitle=Structural+analysis+by+X-ray+crystallography+and+calorimetry+of+a+haemagglutinin+component+%28HA1%29+of+the+progenitor+toxin+from+Clostridium+botulinum&rft.au=Inoue%2C+Kaoru%3BSobhany%2C+M%3BTransue%2C+T+R%3BOguma%2C+Keiji%3BPedersen%2C+L+C%3BNegishi%2C+Masahiko&rft.aulast=Inoue&rft.aufirst=Kaoru&rft.date=2003-12-01&rft.volume=149&rft.issue=12&rft.spage=3361&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&rft_id=info:doi/10.1099%2Fmic.0.26586-0 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - X-ray crystallography; Botulism; Hemagglutinins; Crystal structure; Calorimetry; Neurotoxins; Clostridium botulinum DO - http://dx.doi.org/10.1099/mic.0.26586-0 ER - TY - JOUR T1 - Swimming lessons, swimming ability, and the risk of drowning AN - 19225337; 5790604 AB - Drowning is a leading cause of injury related death in many countries. Strategies to prevent these deaths depend upon characteristics of the victim and the specific circumstances surrounding the event. One preventive strategy that may be beneficial for persons of all ages and under nearly all circumstances is increased swimming ability, through some form of swimming instruction. However, a clear protective relationship between increased swimming ability and the risk of drowning has never been demonstrated. Studies focused on children, suggest that swimming ability may confer some protection, although the data are far from conclusive. This paper (1) reviews the current evidence regarding the relationship between swimming ability, swimming lessons and the risk of drowning, (2) reviews the past and present recommendations for swimming instruction and (3) outlines future research needs. JF - Injury Control and Safety Promotion AU - Brenner, R A AU - Saluja, G AU - Smith, G S AD - Division of Epidemiology, Statistics, and Prevention Research National Institute of Child Health and Human Development, 6100 Executive Blvd. Room 7B03 Bethesda, MD 20892, USA, BrennerR@NIH.GOV Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 211 EP - 216 VL - 10 IS - 4 SN - 1566-0974, 1566-0974 KW - drowning KW - swimming KW - Risk Abstracts; Health & Safety Science Abstracts KW - Mortality KW - Accidents KW - Recreation areas KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19225337?accountid=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=Injury+Control+and+Safety+Promotion&rft.atitle=Swimming+lessons%2C+swimming+ability%2C+and+the+risk+of+drowning&rft.au=Brenner%2C+R+A%3BSaluja%2C+G%3BSmith%2C+G+S&rft.aulast=Brenner&rft.aufirst=R&rft.date=2003-12-01&rft.volume=10&rft.issue=4&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Injury+Control+and+Safety+Promotion&rft.issn=15660974&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 - Recreation areas; Accidents; Mortality ER - TY - JOUR T1 - The distribution of RNA polymerase in Escherichia coli is dynamic and sensitive to environmental cues AN - 19217023; 5782492 AB - Despite extensive genetic, biochemical and structural studies on Escherichia coli RNA polymerase (RNAP), little is known about its location and distribution in response to environmental changes. To visualize the RNAP by fluorescence microscopy in E. coli under different physiological conditions, we constructed a functional rpoC-gfp gene fusion on the chromosome. We show that, although RNAP is located in the nucleoid and at its periphery, the distribution of RNAP is dynamic and dramatically influenced by cell growth conditions, nutrient starvation and overall transcription activity inside the cell. Moreover, mutational analysis suggests that the stable RNA synthesis plays an important role in nucleoid condensation. JF - Molecular Microbiology AU - Cabrera, JE AU - Jin, D J AD - Laboratory of Molecular Biology, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA., djjin@helix.nih.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 1493 EP - 1505 PB - Blackwell Science Ltd VL - 50 IS - 5 SN - 0950-382X, 0950-382X KW - GFP gene KW - gfp gene KW - rpoC gene KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Starvation KW - DNA-directed RNA polymerase KW - Growth KW - Fluorescence KW - Escherichia coli KW - Nucleoids KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19217023?accountid=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+distribution+of+RNA+polymerase+in+Escherichia+coli+is+dynamic+and+sensitive+to+environmental+cues&rft.au=Cabrera%2C+JE%3BJin%2C+D+J&rft.aulast=Cabrera&rft.aufirst=JE&rft.date=2003-12-01&rft.volume=50&rft.issue=5&rft.spage=1493&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2003.03805.x LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Starvation; Growth; DNA-directed RNA polymerase; Fluorescence; Nucleoids; Escherichia coli DO - http://dx.doi.org/10.1046/j.1365-2958.2003.03805.x ER - TY - JOUR T1 - The Octapeptidic End of the C-Terminal Tail of Histone H2A Is Cleaved Off in Cells Exposed to Carcinogenic Nickel(II) AN - 19211570; 5800965 AB - We have demonstrated previously that Ni(II) binds to the C-terminal -TESHHKAKGK motif of isolated bovine histone H2A. At physiological pH, the bound Ni(II) assists in hydrolysis of the E-S peptide bond in this motif that results in a cleavage of the terminal octapeptide SHHKAKGK off the histone's C-tail. To test if the hydrolysis could also occur in living cells, we cultured CHO (Chinese hamster ovary), NRK-52 (rat renal tubular epithelium), and HPL1D (human lung epithelium) cells with 0.1-1 mM Ni(II) for 3-7 days. As found by gel electrophoresis, Western blotting, and liquid chromatography/mass spectrometry, histones extracted from the cells contained a new fraction of histone H2A lacking the terminal octapeptide (q-H2A). The abundance of q-H2A increased with Ni(II) concentration and exposure time. It can be anticipated that the truncation of histone H2A may alter chromatin structure and affect gene expression. The present results provide evidence for novel mechanisms of epigenetic effects of Ni(II) that may be involved in nickel toxicity and carcinogenesis. JF - Chemical Research in Toxicology AU - Karaczyn, A A AU - Bal, W AU - North, S L AU - Bare, R M AU - Hoang, V M AU - Fisher, R J AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, NCI at Frederick, Frederick, Maryland 21702, USA Y1 - 2003/12// PY - 2003 DA - December 2003 SP - 1555 EP - 1559 PB - American Chemical Society, P.O. Box 182426 Columbus OH 43218-2426 USA, [mailto:service@acs.org] VL - 16 IS - 12 SN - 0893-228X, 0893-228X KW - cleavage KW - histone H2A KW - Toxicology Abstracts KW - CHO cells KW - Heavy metals KW - Nickel KW - Carcinogens KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19211570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=The+Octapeptidic+End+of+the+C-Terminal+Tail+of+Histone+H2A+Is+Cleaved+Off+in+Cells+Exposed+to+Carcinogenic+Nickel%28II%29&rft.au=Karaczyn%2C+A+A%3BBal%2C+W%3BNorth%2C+S+L%3BBare%2C+R+M%3BHoang%2C+V+M%3BFisher%2C+R+J%3BKasprzak%2C+K+S&rft.aulast=Karaczyn&rft.aufirst=A&rft.date=2003-12-01&rft.volume=16&rft.issue=12&rft.spage=1555&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/10.1021%2Ftx0300277 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - CHO cells; Heavy metals; Nickel; Carcinogens DO - http://dx.doi.org/10.1021/tx0300277 ER - TY - JOUR T1 - Parallelism and dissociation in the actions of an Aroclor 1260-based transformer fluid on testicular androgenesis and antioxidant enzymes AN - 18894646; 5779062 AB - The mechanism by which Aroclors and other polychlorinated biphenyls (PCBs) inhibit testicular androgenesis in vivo and in vitro has not been characterized. Here we studied in adult rats the effects of intratesticular (itt), intraperitoneal (ip) and by gavage (po) administration of Pyralene, an Aroclor 1260-based transformer fluid, on testicular androgenesis and oxidative status in androgen-producing interstitial cells and liver. Pyralene markedly decreased in vitro agonist stimulated androgenesis 24 h after bilateral itt- injection (25 mu g/testis), 24 h and 96 h after single ip-injection (10 and 50 mg/kg body weight), and 96 h after po-administration (7x10 mg and 7x50 mg/kg body weight daily). Inhibited androgenesis was accompanied by changes in the activity of antioxidant enzymes (AOEs) in interstitial cells after local itt-treatment and occasionally after systemic Pyralene application. Among changes in the activity, glutathione peroxidase and catalase reflected relatively well the toxicity of Pyralene in these cells. In liver, glutathione- S-transferase (GST) and glutathione peroxidase activities were enhanced after po-treatment and total glutathione (tGSH) content and lipid peroxidation (LP) were enhanced after ip-administration. These results indicate that Pyralene inhibits androgenesis independently of the method of its administration. The results also suggest that changes in the oxidative status in testicular milieu are not critical for Pyralene-induced inhibition of androgenesis. JF - Toxicology AU - Andric, N L AU - Andric, SA AU - Zoric, S N AU - Kostic, T S AU - Stojilkovic, S S AU - Kovacevic, R Z AD - Department of Biology and Ecology, Faculty of Sciences, 21000, Novi Sad, Serbia and Montenegro, stankos@helix.nih.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 65 EP - 75 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 194 IS - 1-2 SN - 0300-483X, 0300-483X KW - Aroclor 1260 KW - androgenesis KW - rats KW - transformer fluids KW - Toxicology Abstracts KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18894646?accountid=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&rft.atitle=Parallelism+and+dissociation+in+the+actions+of+an+Aroclor+1260-based+transformer+fluid+on+testicular+androgenesis+and+antioxidant+enzymes&rft.au=Andric%2C+N+L%3BAndric%2C+SA%3BZoric%2C+S+N%3BKostic%2C+T+S%3BStojilkovic%2C+S+S%3BKovacevic%2C+R+Z&rft.aulast=Andric&rft.aufirst=N&rft.date=2003-12-01&rft.volume=194&rft.issue=1-2&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2Fj.tox.2003.08.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.tox.2003.08.002 ER - TY - JOUR T1 - Immunogenicity of Multiple Gene and Clade Human Immunodeficiency Virus Type 1 DNA Vaccines AN - 18891151; 5752086 AB - The ability to elicit an immune response to a spectrum of human immunodeficiency virus type 1 (HIV-1) gene products from divergent strains is a desirable feature of an AIDS vaccine. In this study, we examined combinations of plasmids expressing multiple HIV-1 genes from different clades for their ability to elicit humoral and cellular immune responses in mice. Immunization with a modified Env, gp145[Delta] CFI, in combination with a Gag-Pol-Nef fusion protein plasmid elicited similar CD4 super(+) and CD8 super(+) cellular responses to immunization with either vector alone. Further, when mice were immunized with a mixture of Env from three clades, A, B, and C, together with Gag-Pol-Nef, the overall potency and balance of CD4 super(+)- and CD8 super(+)-T-cell responses to all viral antigens were similar, with only minor differences noted. In addition, plasmid mixtures elicited antibody responses comparable to those from individual inoculations. These findings suggest that a multigene and multiclade vaccine, including components from A, B, and C Env and Gag-Pol-Nef, can broaden antiviral immune responses without immune interference. Such combinations of immunogens may help to address concerns about viral genetic diversity for a prospective HIV-1 vaccine. JF - Journal of Virology AU - Kong, W-P AU - Huang, Y AU - Yang, Z-Y AU - Chakrabarti, B K AU - Moodie, Z AU - Nabel, G J AD - Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 40, Room 4502, MSC 3005, 40 Convent Dr., Bethesda, MD 20892-3005, gnabel@nih.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 12764 EP - 12772 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 77 IS - 23 SN - 0022-538X, 0022-538X KW - HIV-1 KW - man KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - F 06807:Active immunization KW - V 22003:AIDS: Immunological aspects KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews KW - N 14800:Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18891151?accountid=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=Immunogenicity+of+Multiple+Gene+and+Clade+Human+Immunodeficiency+Virus+Type+1+DNA+Vaccines&rft.au=Kong%2C+W-P%3BHuang%2C+Y%3BYang%2C+Z-Y%3BChakrabarti%2C+B+K%3BMoodie%2C+Z%3BNabel%2C+G+J&rft.aulast=Kong&rft.aufirst=W-P&rft.date=2003-12-01&rft.volume=77&rft.issue=23&rft.spage=12764&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.77.23.12764-12772.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JVI.77.23.12764-12772.2003 ER - TY - JOUR T1 - Cell balance equation for chemotactic bacteria with a biphasic tumbling frequency AN - 17902133; 5858643 AB - Alt's three-dimensional cell balance equation characterizing the chemotactic bacteria was analyzed under the presence of one-dimensional spatial chemoattractant gradients. Our work differs from that of others who have developed rather general models for chemotaxis in the use of a non-smooth anisotropic tumbling frequency function that responds biphasically to the combined temporal and spatial chemoattractant gradients. General three-dimensional expressions for the bacterial transport parameters were derived for chemotactic bacteria, followed by a perturbation analysis under the planar geometry. The bacterial random motility and chemotaxis were summarized by a motility tensor and a chemotactic velocity vector, respectively. The consequence of invoking the diffusion-approximation assumption and using intrinsic one-dimensional models with modified cellular swimming speeds was investigated by numerical simulations. Characterizing the bacterial random orientation after tumbles by a turn angle probability distribution function, we found that only the first-order angular moment of this turn angle probability distribution is important in influencing the bacterial long-term transport. JF - Journal of Mathematical Biology AU - Chen, K C AU - Ford, R M AU - Cummings, P T AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 518 EP - 546 VL - 47 IS - 6 SN - 0303-6812, 0303-6812 KW - Cell balance equation KW - Chemoreception Abstracts; Microbiology Abstracts B: Bacteriology KW - Bacteria KW - Swimming KW - Orientation KW - Mathematical models KW - Gradients KW - Attractants KW - Chemotaxis KW - Models KW - Motility KW - Distribution KW - Chemotactic factors KW - J 02721:Cell cycle, morphology and motility KW - R 18007:Chemotaxis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17902133?accountid=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+Mathematical+Biology&rft.atitle=Cell+balance+equation+for+chemotactic+bacteria+with+a+biphasic+tumbling+frequency&rft.au=Chen%2C+K+C%3BFord%2C+R+M%3BCummings%2C+P+T&rft.aulast=Chen&rft.aufirst=K&rft.date=2003-12-01&rft.volume=47&rft.issue=6&rft.spage=518&rft.isbn=&rft.btitle=&rft.title=Journal+of+Mathematical+Biology&rft.issn=03036812&rft_id=info:doi/10.1007%2Fs00285-003-0216-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mathematical models; Bacteria; Swimming; Chemotaxis; Gradients; Orientation; Chemotactic factors; Attractants; Motility; Distribution; Models DO - http://dx.doi.org/10.1007/s00285-003-0216-8 ER - TY - JOUR T1 - Exploring semantic groups through visual approaches AN - 17708152; 5827063 AB - Objectives. We investigate several visual approaches for exploring semantic groups, a grouping of semantic types from the Unified Medical Language System (UMLS) semantic network. We are particularly interested in the semantic coherence of the groups, and we use the semantic relationships as important indicators of that coherence. Methods. First, we create a radial representation of the number of relationships among the groups, generating a profile for each semantic group. Second, we show that, in our partition, the relationships are organized around a limited number of pivot groups and that partitions created at random do not exhibit this property. Finally, we use correspondence analysis to visualize groupings resulting from the association between semantic types and the relationships. Results. The three approaches provide different views on the semantic groups and help detect potential inconsistencies. They make outliers immediately apparent, and, thus, serve as a tool for auditing and validating both the semantic network and the semantic groups. JF - Journal of Biomedical Informatics AU - Bodenreider, O AU - McCray, A T AD - Department of Health and Human Services, National Institutes of Health, National Library of Medicine, Lister Hill National Center for Biomedical Communications, MS 43, Bldg 38A Rm B1N28U, 8600 Rockville Pike, Bethesda, MD 20894, USA, olivier@nlm.nih.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 414 EP - 432 PB - Academic Press, Inc., 525 B St. Ste. 1900 San Diego CA 92101-4495 USA, [mailto:apsubs@acad.com] VL - 36 IS - 6 SN - 1532-0464, 1532-0464 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Language KW - Bioinformatics KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17708152?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biomedical+Informatics&rft.atitle=Exploring+semantic+groups+through+visual+approaches&rft.au=Bodenreider%2C+O%3BMcCray%2C+A+T&rft.aulast=Bodenreider&rft.aufirst=O&rft.date=2003-12-01&rft.volume=36&rft.issue=6&rft.spage=414&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomedical+Informatics&rft.issn=15320464&rft_id=info:doi/10.1016%2Fj.jbi.2003.11.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; Language DO - http://dx.doi.org/10.1016/j.jbi.2003.11.002 ER - TY - JOUR T1 - The interaction of domain knowledge and linguistic structure in natural language processing: interpreting hypernymic propositions in biomedical text AN - 17702978; 5827065 AB - Interpretation of semantic propositions in free-text documents such as MEDLINE citations would provide valuable support for biomedical applications, and several approaches to semantic interpretation are being pursued in the biomedical informatics community. In this paper, we describe a methodology for interpreting linguistic structures that encode hypernymic propositions, in which a more specific concept is in a taxonomic relationship with a more general concept. In order to effectively process these constructions, we exploit underspecified syntactic analysis and structured domain knowledge from the Unified Medical Language System (UMLS). After introducing the syntactic processing on which our system depends, we focus on the UMLS knowledge that supports interpretation of hypernymic propositions. We first use semantic groups from the Semantic Network to ensure that the two concepts involved are compatible; hierarchical information in the Metathesaurus then determines which concept is more general and which more specific. A preliminary evaluation of a sample based on the semantic group Chemicals and Drugs provides 83% precision. An error analysis was conducted and potential solutions to the problems encountered are presented. The research discussed here serves as a paradigm for investigating the interaction between domain knowledge and linguistic structure in natural language processing, and could also make a contribution to research on automatic processing of discourse structure. Additional implications of the system we present include its integration in advanced semantic interpretation processors for biomedical text and its use for information extraction in specific domains. The approach has the potential to support a range of applications, including information retrieval and ontology engineering. JF - Journal of Biomedical Informatics AU - Rindflesch, T C AU - Fiszman, M AD - Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Department of Health and Human Services, 8600 Rockville Pike, Bethesda, MD 20894, USA, tcr@nlm.nih.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 462 EP - 477 PB - Academic Press, Inc., 525 B St. Ste. 1900 San Diego CA 92101-4495 USA, [mailto:apsubs@acad.com] VL - 36 IS - 6 SN - 1532-0464, 1532-0464 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Information processing KW - Language KW - Bioinformatics KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17702978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biomedical+Informatics&rft.atitle=The+interaction+of+domain+knowledge+and+linguistic+structure+in+natural+language+processing%3A+interpreting+hypernymic+propositions+in+biomedical+text&rft.au=Rindflesch%2C+T+C%3BFiszman%2C+M&rft.aulast=Rindflesch&rft.aufirst=T&rft.date=2003-12-01&rft.volume=36&rft.issue=6&rft.spage=462&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomedical+Informatics&rft.issn=15320464&rft_id=info:doi/10.1016%2Fj.jbi.2003.11.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bioinformatics; Language; Information processing DO - http://dx.doi.org/10.1016/j.jbi.2003.11.003 ER - TY - JOUR T1 - Psychosocial Predictors of Increased Smoking Stage Among Sixth Graders AN - 17696252; 5980909 AB - To identify predictors of increases in smoking stage among sixth graders. At the beginning and end of sixth grade, 973 students completed surveys. Multivariate, partial proportional odds analyses were conducted. Time 1 intenders were 4 times more likely than never users to smoke at Time 2. In adjusted analyses, female sex, white race, peers, and perceived prevalence were positively associated with an increase in smoking stage, and social competence, parental expectations, and parental monitoring were negatively associated with an increase in smoking stage. Early adolescent smoking advanced in stages; intent predicted initiation; peer and parent influences were independently associated with increases in smoking stage. JF - American Journal of Health Behavior AU - Simons-Morton, B G AU - Haynie, D L AD - Prevention Research Branch, DESPR, NICHD, 6100 Executive Blvd., Rm 7B05, Rockville, MD 20852-7510, USA, MORTONB@exchange.nih.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 592 EP - 602 VL - 27 IS - 6 SN - 1087-3244, 1087-3244 KW - Physical Education Index KW - Smoking KW - Peers KW - Social behavior KW - Tobacco KW - Surveys KW - Health (behavior) KW - Psychosocial factors KW - Parental involvement KW - Children KW - PE 120:Sport: Psychology, Sociology & History UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17696252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Health+Behavior&rft.atitle=Psychosocial+Predictors+of+Increased+Smoking+Stage+Among+Sixth+Graders&rft.au=Simons-Morton%2C+B+G%3BHaynie%2C+D+L&rft.aulast=Simons-Morton&rft.aufirst=B&rft.date=2003-12-01&rft.volume=27&rft.issue=6&rft.spage=592&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Health+Behavior&rft.issn=10873244&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Health (behavior); Psychosocial factors; Tobacco; Peers; Surveys; Children; Parental involvement; Social behavior; Smoking ER - TY - JOUR T1 - Education and Training for Radiation Scientists: Radiation Research Program and American Society of Therapeutic Radiology and Oncology Workshop, Bethesda, Maryland, May 12-14, 2003 AN - 17682272; 5775695 AB - Current and potential shortfalls in the number of radiation scientists stand in sharp contrast to the emerging scientific opportunities and the need for new knowledge to address issues of cancer survivorship and radiological and nuclear terrorism. In response to these challenges, workshops organized by the Radiation Research Program (RRP), National Cancer Institute (NCI) (Radiat. Res. 157, 204-223, 2002; Radiat. Res. 159, 812-834, 2003), and National Institute of Allergy and Infectious Diseases (NIAID) (Nature, 421, 787, 2003) have engaged experts from a range of federal agencies, academia and industry. This workshop, Education and Training for Radiation Scientists, addressed the need to establish a sustainable pool of expertise and talent for a wide range of activities and careers related to radiation biology, oncology and epidemiology. Although fundamental radiation chemistry and physics are also critical to radiation sciences, this workshop did not address workforce needs in these areas. The recommendations include: (1) Establish a National Council of Radiation Sciences to develop a strategy for increasing the number of radiation scientists. The strategy includes NIH training grants, interagency cooperation, interinstitutional collaboration among universities, and active involvement of all stakeholders. (2) Create new and expanded training programs with sustained funding. These may take the form of regional Centers of Excellence for Radiation Sciences. (3) Continue and broaden educational efforts of the American Society for Therapeutic Radiology and Oncology (ASTRO), the American Association for Cancer Research (AACR), the Radiological Society of North America (RSNA), and the Radiation Research Society (RRS). (4) Foster education and training in the radiation sciences for the range of career opportunities including radiation oncology, radiation biology, radiation epidemiology, radiation safety, health /government policy, and industrial research. (5) Educate other scientists and the general public on the quantitative, basic, molecular, translational and applied aspects of radiation sciences. JF - Radiation Research AU - Coleman, C N AU - Stone, H B AU - Alexander, G A AU - Barcellos-Hoff, M H AU - Bedford, J S AU - Bristow, R G AU - Dynlacht, J R AU - Fuks, Z AU - Gorelic, L S AU - Hill, R P AU - Joiner, M C AU - Liu, F AU - McBride, W H AU - McKenna, W G AU - Powell, S N AU - Robbins, MEC AU - Rockwell, S AU - Schiff, P B AU - Shaw, E G AU - Siemann, D W AU - Travis, EL AU - Wallner, P E AU - Wong, RSL AU - Zeman, E M AD - Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, ccoleman@mail.nih.gov Y1 - 2003/12// PY - 2003 DA - Dec 2003 SP - 729 EP - 737 PB - The Radiation Research Society VL - 160 IS - 6 SN - 0033-7587, 0033-7587 KW - Sustainability Science Abstracts KW - M3 1010:Issues in Sustainable Development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17682272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Assamodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+Research&rft.atitle=Education+and+Training+for+Radiation+Scientists%3A+Radiation+Research+Program+and+American+Society+of+Therapeutic+Radiology+and+Oncology+Workshop%2C+Bethesda%2C+Maryland%2C+May+12-14%2C+2003&rft.au=Coleman%2C+C+N%3BStone%2C+H+B%3BAlexander%2C+G+A%3BBarcellos-Hoff%2C+M+H%3BBedford%2C+J+S%3BBristow%2C+R+G%3BDynlacht%2C+J+R%3BFuks%2C+Z%3BGorelic%2C+L+S%3BHill%2C+R+P%3BJoiner%2C+M+C%3BLiu%2C+F%3BMcBride%2C+W+H%3BMcKenna%2C+W+G%3BPowell%2C+S+N%3BRobbins%2C+MEC%3BRockwell%2C+S%3BSchiff%2C+P+B%3BShaw%2C+E+G%3BSiemann%2C+D+W%3BTravis%2C+EL%3BWallner%2C+P+E%3BWong%2C+RSL%3BZeman%2C+E+M&rft.aulast=Coleman&rft.aufirst=C&rft.date=2003-12-01&rft.volume=160&rft.issue=6&rft.spage=729&rft.isbn=&rft.btitle=&rft.title=Radiation+Research&rft.issn=00337587&rft_id=info:doi/10.1043%2F0033-7587%282003%29160%280729%3AEATFRS%292.0.CO%3B2 L2 - http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0033-7587&volume=160&page=729 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1043/0033-7587(2003)160(0729:EATFRS)2.0.CO;2 ER - TY - JOUR T1 - Induction of redox changes, inducible nitric oxide synthase and cyclooxygenase-2 by chronic cadmium exposure in mouse peritoneal macrophages. AN - 71344421; 14581164 AB - Redox changes and the secretion of inflammatory mediators were investigated in resident peritoneal macrophages of mice chronically exposed to cadmium (Cd, 15 ppm for 2 months) through drinking water. Our results showed that in vivo Cd exposure altered the redox balance in mouse peritoneal macrophages, leading to excessive production of reactive oxygen species (ROS) that overwhelmed the antioxidant defenses. It also led to increased lipid peroxidation and arachidonic acid (AA) release, higher nitric oxide and prostaglandin E(2) (PGE(2)) production, and induction of inducible nitric oxide synthase and cyclooxygenase-2 compared with control macrophages. Oxidative stress and inflammation could be important processes operating in the modulation of mouse macrophage physiology induced by chronic Cd exposure. JF - Toxicology letters AU - Ramirez, Dario C AU - Gimenez, Maria Sofia AD - Laboratory of Molecular Biochemistry, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, Avenida Ejercito de los Andes 950, 5700 San Luis, Argentina. ramirez1@niehs.nih.gov Y1 - 2003/11/30/ PY - 2003 DA - 2003 Nov 30 SP - 121 EP - 132 VL - 145 IS - 2 SN - 0378-4274, 0378-4274 KW - Isoenzymes KW - 0 KW - Reactive Oxygen Species KW - Cadmium KW - 00BH33GNGH KW - Nitric Oxide KW - 31C4KY9ESH KW - Glucosephosphate Dehydrogenase KW - EC 1.1.1.49 KW - Catalase KW - EC 1.11.1.6 KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Immunoblotting KW - Nitric Oxide -- blood KW - Mice KW - Mice, Inbred BALB C KW - Glucosephosphate Dehydrogenase -- metabolism KW - Oxidation-Reduction KW - Catalase -- metabolism KW - Dinoprostone -- blood KW - Glutathione Peroxidase -- metabolism KW - Enzyme Induction -- drug effects KW - Male KW - Cadmium -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Isoenzymes -- biosynthesis KW - Cadmium -- toxicity KW - Macrophages, Peritoneal -- drug effects KW - Nitric Oxide Synthase -- metabolism KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Isoenzymes -- metabolism KW - Cadmium Poisoning -- enzymology KW - Nitric Oxide Synthase -- biosynthesis KW - Macrophages, Peritoneal -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71344421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Induction+of+redox+changes%2C+inducible+nitric+oxide+synthase+and+cyclooxygenase-2+by+chronic+cadmium+exposure+in+mouse+peritoneal+macrophages.&rft.au=Ramirez%2C+Dario+C%3BGimenez%2C+Maria+Sofia&rft.aulast=Ramirez&rft.aufirst=Dario&rft.date=2003-11-30&rft.volume=42&rft.issue=8&rft.spage=2275&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-02 N1 - Date created - 2003-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Compartment-specific protection of iron-sulfur proteins by superoxide dismutase. AN - 71400387; 12972424 AB - Iron and oxygen are essential but potentially toxic constituents of most organisms, and their transport is meticulously regulated both at the cellular and systemic levels. Compartmentalization may be a homeostatic mechanism for isolating these biological reactants in cells. To investigate this hypothesis, we have undertaken a genetic analysis of the interaction between iron and oxygen metabolism in Drosophila. We show that Drosophila iron regulatory protein-1 (IRP1) registers cytosolic iron and oxidative stress through its labile iron sulfur cluster by switching between cytosolic aconitase and RNA-binding functions. IRP1 is strongly activated by silencing and genetic mutation of the cytosolic superoxide dismutase (Sod1), but is unaffected by silencing of mitochondrial Sod2. Conversely, mitochondrial aconitase activity is relatively insensitive to loss of Sod1 function, but drops dramatically if Sod2 activity is impaired. This strongly suggests that the mitochondrial boundary limits the range of superoxide reactivity in vivo. We also find that exposure of adults to paraquat converts cytosolic aconitase to IRP1 but has no affect on mitochondrial aconitase, indicating that paraquat generates superoxide in the cytosol but not in mitochondria. Accordingly, we find that transgene-mediated overexpression of Sod2 neither enhances paraquat resistance in Sod1+ flies nor compensates for lack of SOD1 activity in Sod1-null mutants. We conclude that in vivo, superoxide is confined to the subcellular compartment in which it is formed, and that the mitochondrial and cytosolic SODs provide independent protection to compartment-specific protein iron-sulfur clusters against attack by superoxide generated under oxidative stress within those compartments. JF - The Journal of biological chemistry AU - Missirlis, Fanis AU - Hu, Jianguo AU - Kirby, Kim AU - Hilliker, Arthur J AU - Rouault, Tracey A AU - Phillips, John P AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/11/28/ PY - 2003 DA - 2003 Nov 28 SP - 47365 EP - 47369 VL - 278 IS - 48 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - Herbicides KW - Iron-Sulfur Proteins KW - SOD1 protein, human KW - Superoxides KW - 11062-77-4 KW - RNA KW - 63231-63-0 KW - Iron KW - E1UOL152H7 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Superoxide Dismutase-1 KW - superoxide dismutase 2 KW - Aconitate Hydratase KW - EC 4.2.1.3 KW - Iron Regulatory Protein 1 KW - Paraquat KW - PLG39H7695 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Paraquat -- pharmacology KW - Animals KW - Cytosol -- metabolism KW - Dose-Response Relationship, Drug KW - Oxygen -- metabolism KW - Cytosol -- enzymology KW - Mitochondria -- enzymology KW - Transgenes KW - Iron Regulatory Protein 1 -- metabolism KW - Protein Binding KW - Iron -- metabolism KW - Aconitate Hydratase -- chemistry KW - RNA -- metabolism KW - DNA, Complementary -- metabolism KW - Oxidative Stress KW - RNA Interference KW - Time Factors KW - Mutation KW - Drosophila KW - Cell Line KW - Iron-Sulfur Proteins -- chemistry KW - Superoxide Dismutase -- metabolism KW - Superoxide Dismutase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71400387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Compartment-specific+protection+of+iron-sulfur+proteins+by+superoxide+dismutase.&rft.au=Missirlis%2C+Fanis%3BHu%2C+Jianguo%3BKirby%2C+Kim%3BHilliker%2C+Arthur+J%3BRouault%2C+Tracey+A%3BPhillips%2C+John+P&rft.aulast=Missirlis&rft.aufirst=Fanis&rft.date=2003-11-28&rft.volume=278&rft.issue=48&rft.spage=47365&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 - 2004-01-12 N1 - Date created - 2003-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repair of and checkpoint response to topoisomerase I-mediated DNA damage. AN - 71437585; 14643436 AB - Topoisomerase I (Top1) catalyzes two transesterification reactions: single-strand DNA cleavage and religation that are normally coupled for the relaxation of DNA supercoiling in transcribing and replicating chromatin. A variety of endogenous DNA modifications, potent anticancer drugs and carcinogens uncouple these two reactions, resulting in the accumulation of Top1 cleavage complexes. Top1 cleavage complexes damage DNA and kill cells by generating replication-mediated DNA double-strand breaks (DSBs) and by stalling transcription complexes. The repair of Top1-mediated DNA lesions involves integrated pathways that are conserved from yeasts to humans. Top1-mediated DNA damage and cell cycle checkpoint responses can be studied biochemically and genetically in yeast and human cells with known genetic defects. Defects in these repair/checkpoint pathways, which promote tumor development, explain, at least in part, the selectivity of camptothecins and other Top1 inhibitors for cancer cells. JF - Mutation research AU - Pommier, Yves AU - Redon, Christophe AU - Rao, V Ashutosh AU - Seiler, Jennifer A AU - Sordet, Olivier AU - Takemura, Haruyuki AU - Antony, Smitha AU - Meng, LingHua AU - Liao, ZhiYong AU - Kohlhagen, Glenda AU - Zhang, HongLiang AU - Kohn, Kurt W AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute/NIH, Building 37, Room 5068, Bethesda, MD 20892-4255, USA. pommier@nih.gov Y1 - 2003/11/27/ PY - 2003 DA - 2003 Nov 27 SP - 173 EP - 203 VL - 532 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Antineoplastic Agents KW - 0 KW - DNA KW - 9007-49-2 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Animals KW - DNA Repair KW - Recombination, Genetic -- drug effects KW - Humans KW - DNA -- metabolism KW - Protein Binding KW - Models, Biological KW - Antineoplastic Agents -- pharmacology KW - DNA Damage KW - DNA Topoisomerases, Type I -- physiology KW - Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71437585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Repair+of+and+checkpoint+response+to+topoisomerase+I-mediated+DNA+damage.&rft.au=Pommier%2C+Yves%3BRedon%2C+Christophe%3BRao%2C+V+Ashutosh%3BSeiler%2C+Jennifer+A%3BSordet%2C+Olivier%3BTakemura%2C+Haruyuki%3BAntony%2C+Smitha%3BMeng%2C+LingHua%3BLiao%2C+ZhiYong%3BKohlhagen%2C+Glenda%3BZhang%2C+HongLiang%3BKohn%2C+Kurt+W&rft.aulast=Pommier&rft.aufirst=Yves&rft.date=2003-11-27&rft.volume=532&rft.issue=1-2&rft.spage=173&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 - 2004-01-20 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacology -- Uncoupling the agony from ecstasy AN - 18898320; 5769325 AB - The recreational use of amphetamine-type stimulants can produce a marked and sometimes lethal increase in body temperature. Here we show that mice deficient in a mitochondrial protein known as UCP-3 (for 'uncoupling protein-3') have a diminished thermogenic response to the drug MDMA (3,4- methylenedioxymethamphetamine, nicknamed 'ecstasy') and so are protected against this dangerously toxic effect. Our findings indicate that UCP-3 is important in MDMA-induced hyperthermia and point to a new therapeutic direction for solving an increasing public-health problem. JF - Nature AU - Mills, E M AU - Banks, M L AU - Sprague, JE AU - Finkel, T AD - Cardiovascular Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1622, USA, j-sprague@onu.edu Y1 - 2003/11/27/ PY - 2003 DA - 2003 Nov 27 SP - 403 EP - 404 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 426 IS - 6965 SN - 0028-0836, 0028-0836 KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18898320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=The+Philosophical+Quarterly&rft.atitle=Of+Minds+and+Molecules%3A+New+Philosophical+Perspectives+on+Chemistry&rft.au=Schummer%2C+Joachim&rft.aulast=Schummer&rft.aufirst=Joachim&rft.date=2003-04-01&rft.volume=53&rft.issue=211&rft.spage=301&rft.isbn=&rft.btitle=&rft.title=The+Philosophical+Quarterly&rft.issn=00318094&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/426403a ER - TY - JOUR T1 - The role of reactive oxygen species on Plasmodium melanotic encapsulation in Anopheles gambiae AN - 19259294; 5831475 AB - Malaria transmission depends on the competence of some Anopheles mosquitoes to sustain Plasmodium development (susceptibility). A genetically selected refractory strain of Anopheles gambiae blocks Plasmodium development, melanizing, and encapsulating the parasite in a reaction that begins with tyrosine oxidation, and involves three quantitative trait loci. Morphological and microarray mRNA expression analysis suggest that the refractory and susceptible strains have broad physiological differences, which are related to the production and detoxification of reactive oxygen species. Physiological studies corroborate that the refractory strain is in a chronic state of oxidative stress, which is exacerbated by blood feeding, resulting in increased steady-state levels of reactive oxygen species, which favor melanization of parasites as well as Sephadex beads. JF - Proceedings of the National Academy of Sciences, USA AU - Kumar, S AU - Christophides, G K AU - Cantera, R AU - Charles, B AU - Han, Y S AU - Meister, S AU - Dimopoulos, G AU - Kafatos, F C AU - Barillas-Mury, C AD - Colorado State University, Department of Microbiology, Immunology, and Pathology, 1619 Campus Delivery, Fort Collins, CO 80523, cbarillas@niaid.nih.gov Y1 - 2003/11/25/ PY - 2003 DA - 2003 Nov 25 SP - 14139 EP - 14144 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 24 SN - 0027-8424, 0027-8424 KW - Culicidae KW - Diptera KW - Encapsulation KW - Reactive oxygen species KW - ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Microbiology Abstracts C: Algology, Mycology & Protozoology; Genetics Abstracts; Entomology Abstracts KW - IMMUNOLOGY KW - Parasites KW - Biological development KW - Immunology KW - Physiology KW - Malaria KW - Hosts KW - Freshwater KW - Defence mechanisms KW - Anopheles gambiae KW - Plasmodium KW - Oxidative stress KW - Aquatic insects KW - K 03090:Protozoa: human KW - G 07361:Protozoans/slime molds KW - Z 05206:Medical & veterinary entomology KW - Q1 08484:Species interactions: parasites and diseases KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19259294?accountid=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=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=The+role+of+reactive+oxygen+species+on+Plasmodium+melanotic+encapsulation+in+Anopheles+gambiae&rft.au=Kumar%2C+S%3BChristophides%2C+G+K%3BCantera%2C+R%3BCharles%2C+B%3BHan%2C+Y+S%3BMeister%2C+S%3BDimopoulos%2C+G%3BKafatos%2C+F+C%3BBarillas-Mury%2C+C&rft.aulast=Kumar&rft.aufirst=S&rft.date=2003-11-25&rft.volume=100&rft.issue=24&rft.spage=14139&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.2036262100 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - Parasites; Biological development; Immunology; Physiology; Malaria; Hosts; Defence mechanisms; Aquatic insects; Reactive oxygen species; Oxidative stress; Encapsulation; Plasmodium; Anopheles gambiae; Freshwater DO - http://dx.doi.org/10.1073/pnas.2036262100 ER - TY - JOUR T1 - Linking the growth inhibition response from the National Cancer Institute's anticancer screen to gene expression levels and other molecular target data. AN - 71396806; 14630650 AB - Data mining tools are proposed to establish mechanistic connections between chemotypes and specific cellular functions. Drawing on a previous study that classified the cellular response patterns of growth inhibition measurements log( GI(50)) from the National Cancer Institute's (NCI's) anticancer screen, we have examined additional data for mRNA expression, sets of known molecular targets and mutational status against these same tumor cell lines to relate chemosensitivity more precisely to biochemical pathways. Our analysis finds that gene expression levels do not, in general, correlate with log(GI(50)) measurements, instead they reflect a generic toxic condition. Within the remaining set of non-generic conditions, examples were found where a correlation suggesting a biochemical basis for cellular cytotoxicity could be supported. These included reconfirmation of previously observed associations between mutant and wild-type status of p53, and chemosensitivity to alkylating agents, while extending these results to reveal associations with gamma-induced expressions of MDM2, WAF1 and GADD45, signals that were not apparent in measurements of basal mRNA expression levels for any of these genes. Additional examinations revealed that mRNA expression levels directly correlated with paclitaxel chemosensitivity to mitosis, while also identifying additional chemotypes as P-glycoprotein substrates. Our analysis revealed well-known direct associations between p16 mutant status and chemotypes implicated in cell cycle control, and extended these results to include expression levels for three additional tyrosine kinase proteins (TEK, transgelin and hCdc4). Links were also found that suggested associations between chemosensitivity and the endocrine, paracrine ligand-receptor loops, via expression of the adrenergic receptor, calcium second messenger pathways via expression levels of carbonic anhydrase and cellular communication pathways via fibrillin. JF - Bioinformatics (Oxford, England) AU - Wallqvist, Anders AU - Rabow, Alfred A AU - Shoemaker, Robert H AU - Sausville, Edward A AU - Covell, David G AD - Science Applications International Corporation, National Cancer Institute at Frederick, National Institutes of Health Frederick, MD 21702, USA. wallqvist@ncifrcf.gov Y1 - 2003/11/22/ PY - 2003 DA - 2003 Nov 22 SP - 2212 EP - 2224 VL - 19 IS - 17 SN - 1367-4803, 1367-4803 KW - Antineoplastic Agents KW - 0 KW - Biomarkers, Tumor KW - Growth Inhibitors KW - Index Medicus KW - United States KW - Gene Targeting -- methods KW - Humans KW - National Institutes of Health (U.S.) KW - Growth Inhibitors -- pharmacology KW - Lethal Dose 50 KW - Cell Division -- drug effects KW - Cell Line, Tumor -- drug effects KW - Cell Line, Tumor -- metabolism KW - Gene Expression Profiling -- methods KW - Biomarkers, Tumor -- metabolism KW - Biomarkers, Tumor -- genetics KW - Antineoplastic Agents -- classification KW - Databases, Factual KW - Drug Screening Assays, Antitumor -- standards KW - Information Storage and Retrieval -- methods KW - Drug Screening Assays, Antitumor -- methods KW - Antineoplastic Agents -- chemistry KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Antineoplastic Agents -- pharmacology KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71396806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioinformatics+%28Oxford%2C+England%29&rft.atitle=Linking+the+growth+inhibition+response+from+the+National+Cancer+Institute%27s+anticancer+screen+to+gene+expression+levels+and+other+molecular+target+data.&rft.au=Wallqvist%2C+Anders%3BRabow%2C+Alfred+A%3BShoemaker%2C+Robert+H%3BSausville%2C+Edward+A%3BCovell%2C+David+G&rft.aulast=Wallqvist&rft.aufirst=Anders&rft.date=2003-11-22&rft.volume=19&rft.issue=17&rft.spage=2212&rft.isbn=&rft.btitle=&rft.title=Bioinformatics+%28Oxford%2C+England%29&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-22 N1 - Date created - 2003-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arginine 222 in the pre-transmembrane domain 1 of 5-HT3A receptors links agonist binding to channel gating. AN - 71380514; 12970351 AB - Ligand-gated ion channels are integral membrane proteins that mediate fast synaptic transmission. Molecular biological techniques have been extensively used for determining the structure-function relationships of ligand-gated ion channels. However, the transduction mechanisms that link agonist binding to channel gating remain poorly understood. Arginine 222 (Arg-222), located at the distal end of the extracellular N-terminal domain immediately preceding the first transmembrane domain (TM1), is conserved in all 5-HT3A receptors and alpha7-nicotinic acetylcholine receptors that have been cloned. To elucidate the possible role of Arg-222 in the function of 5-HT3A receptors, we mutated the arginine residue to alanine (Ala) and expressed both the wild-type and the mutant receptor in human embryonic kidney 293 cells. Functional studies of expressed wild-type and mutant receptors revealed that the R222A mutation increased the apparent potency of the full agonist, serotonin (5-HT), and the partial agonist, 2-Me-5-HT, 5- and 12-fold, respectively. In addition, the mutation increased the efficacy of 2-Me-5-HT and converted it from a partial agonist to a full agonist. Furthermore, this mutation also converted the 5-HT3 receptor antagonist/very weak partial agonist, apomorphine, to a potent agonist. Kinetic analysis revealed that the R222A mutation increased the rate of receptor activation and desensitization but did not affect rate of deactivation. The results suggest that the pre-TM1 amino acid residue Arg-222 may be involved in the transduction mechanism linking agonist binding to channel gating in 5-HT3A receptors. JF - The Journal of biological chemistry AU - Hu, Xiang-Qun AU - Zhang, Li AU - Stewart, Randall R AU - Weight, Forrest F AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism/NIH, Park Building Room 150, Bethesda, MD 20892-8115, USA. xhu@mail.nih.gov Y1 - 2003/11/21/ PY - 2003 DA - 2003 Nov 21 SP - 46583 EP - 46589 VL - 278 IS - 47 SN - 0021-9258, 0021-9258 KW - Receptors, Serotonin, 5-HT3 KW - 0 KW - Serotonin 5-HT3 Receptor Agonists KW - Serotonin KW - 333DO1RDJY KW - Arginine KW - 94ZLA3W45F KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Serotonin -- pharmacology KW - Animals KW - Apomorphine -- pharmacology KW - Humans KW - Serotonin -- analogs & derivatives KW - Amino Acid Sequence KW - Mice KW - Electrophysiology KW - Mutagenesis, Site-Directed KW - Transfection KW - Kinetics KW - Point Mutation KW - Protein Structure, Tertiary KW - Cell Line KW - Receptors, Serotonin, 5-HT3 -- physiology KW - Receptors, Serotonin, 5-HT3 -- chemistry KW - Ion Channel Gating -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71380514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Arginine+222+in+the+pre-transmembrane+domain+1+of+5-HT3A+receptors+links+agonist+binding+to+channel+gating.&rft.au=Hu%2C+Xiang-Qun%3BZhang%2C+Li%3BStewart%2C+Randall+R%3BWeight%2C+Forrest+F&rft.aulast=Hu&rft.aufirst=Xiang-Qun&rft.date=2003-11-21&rft.volume=278&rft.issue=47&rft.spage=46583&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 - 2004-02-03 N1 - Date created - 2003-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thiothalidomides: novel isosteric analogues of thalidomide with enhanced TNF-alpha inhibitory activity. AN - 71367133; 14613324 AB - Thalidomide is being increasingly used in the clinical management of a wide spectrum of immunologically-mediated and infectious diseases, and cancers. However, the mechanisms underlying its pharmacological action are still under investigation. In this regard, oral thalidomide is clinically valuable in the treatment of erythema nodosum leprosum (ENL) and multiple myeloma and effectively reduces tumor necrosis factor-alpha (TNF-alpha) levels and angiogenesis in vivo. This contrasts with its relatively weak effects on TNF-alpha and angiogenesis in in vitro studies and implies that active metabolites contribute to its in vivo pharmacologic action and that specific analogues would be endowed with potent activity. Our focus in the structural modification of thalidomide is toward the discovery of novel isosteric active analogues. In this regard, a series of thiothalidomides and analogues were synthesized and evaluated for their TNF-alpha inhibitory activity against lipopolysacharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC), This was combined with a PBMC viability assay to differentiate reductions in TNF-alpha secretion from cellular toxicity. Two isosteric analogues of thalidomide, compounds 15 and 16, that mostly reflect the parent compound, together with the simple structure, dithioglutarimide 19, potently inhibited TNF-alpha secretion, compared to thalidomide, 1. The mechanism underpinning this most likely is posttranscriptional, as each of these compounds decreased TNF-alpha mRNA stability via its 3'-UTR. The potency of 19 warrants further study and suggests that replacement of the amide carbonyl with a thiocarbonyl may be beneficial for increased TNF-alpha inhibitory action. In addition, an intact phthalimido moiety appeared to be requisite for TNF-alpha inhibitory activity. JF - Journal of medicinal chemistry AU - Zhu, Xiaoxiang AU - Giordano, Tony AU - Yu, Qian-Sheng AU - Holloway, Harold W AU - Perry, Tracy Ann AU - Lahiri, Debomoy K AU - Brossi, Arnold AU - Greig, Nigel H AD - Drug Design & Development Section, Laboratory of Neurosciences, Gerontology Research Center (4E02), Intramural Research Program, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr., Baltimore, Maryland 21224-6825, USA. Y1 - 2003/11/20/ PY - 2003 DA - 2003 Nov 20 SP - 5222 EP - 5229 VL - 46 IS - 24 SN - 0022-2623, 0022-2623 KW - 2,6-piperidinedithione KW - 0 KW - 3' Untranslated Regions KW - Lipopolysaccharides KW - Piperidines KW - RNA, Messenger KW - Thiones KW - Tumor Necrosis Factor-alpha KW - Thalidomide KW - 4Z8R6ORS6L KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Animals KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Luciferases -- metabolism KW - Mice KW - RNA, Messenger -- genetics KW - Structure-Activity Relationship KW - RNA, Messenger -- metabolism KW - In Vitro Techniques KW - Monocytes -- metabolism KW - Genes, Reporter KW - Monocytes -- drug effects KW - Luciferases -- genetics KW - Cell Line KW - Piperidines -- pharmacology KW - Piperidines -- chemical synthesis KW - Thalidomide -- chemical synthesis KW - Thiones -- chemical synthesis KW - Thiones -- pharmacology KW - Tumor Necrosis Factor-alpha -- antagonists & inhibitors KW - Thalidomide -- pharmacology KW - Thalidomide -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71367133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Effect+of+diet+and+housing+on+growth%2C+body+weight%2C+survival+and+tumor+incidences+of+B6C3F1+mice+in+chronic+studies.&rft.au=Rao%2C+Ghanta+N%3BCrockett%2C+Patrick+W&rft.aulast=Rao&rft.aufirst=Ghanta&rft.date=2003-03-01&rft.volume=31&rft.issue=2&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-05 N1 - Date created - 2003-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Local Adeno-Associated Virus-Mediated Interleukin 10 Gene Transfer Has Disease-Modifying Effects in a Murine Model of Sjoegren's Syndrome AN - 19218716; 5790587 AB - Female nonobese diabetic (NOD) mice develop spontaneous autoimmune sialadenitis and loss of salivary flow, and are a widely used model of Sjoegren's syndrome. We examined the feasibility of local salivary gland immunomodulatory gene delivery to alter these sequelae in NOD mice. We constructed recombinant adeno-associated virus (rAAV) vectors encoding either human interleukin 10 (rAAVhIL-10) or beta -galactosidase (rAAVLacZ, control vector). Mice received rAAVhIL-10 or rAAVLacZ by retrograde submandibular ductal instillation either at age 8 weeks (early, before onset of sialadenitis), or at 16 weeks (late, after onset of sialadenitis). As a systemic treatment control, separate mice received intramuscular delivery of rAAVhIL-10 at each time point. Both submandibular and intramuscular delivery of vector led to low circulating levels of hIL-10. After submandibular administration of rAAVhIL-10, salivary flow rates at 20 weeks for both the early and late treatment groups were significantly higher than for both rAAVLacZ-administered and untreated mice. Systemic delivery of rAAVhIL-10 led to improved salivary flow in the late treatment group. Inflammatory infiltrates in submandibular glands, however, were significantly reduced only in mice receiving rAAVhIL-10 locally in the salivary gland compared with mice receiving this vector intramuscularly, or rAAVLacZ or no treatment. In addition, after submandibular rAAVhIL-10 delivery, NOD mice exhibited significantly lower blood glucose, and higher serum insulin, levels than all other groups, indicating some systemic benefit of this treatment. These studies show that expression of hIL-10 by rAAV vectors can have disease-modifying effects in the salivary glands of NOD mice, and suggest that local immunomodulatory gene transfer may be useful for managing the salivary gland pathology in Sjoegren's syndrome. JF - Human Gene Therapy AU - Kok, M R AU - Yamano, Seichii AU - Lodde, B M AU - Wang, Jianghua AU - Couwenhoven, R I AU - Yakar, S AU - Voutetakis, A AU - Leroith, D AU - Schmidt, M AU - Afione, S AU - Pillemer AU - Tsutsui, M T AU - Tak, P P AU - Chiorini, JA AU - Baum, B J AD - GTTB/NIDCR/NIH, 10 Center Drive, MSC 1190, Building 10, Room 1N113, Bethesda, MD 20892, USA, bbaum@dir.nidcr.nih.gov Y1 - 2003/11/20/ PY - 2003 DA - 2003 Nov 20 SP - 1605 EP - 1618 VL - 14 IS - 17 SN - 1043-0342, 1043-0342 KW - mice KW - autoimmune sialadenitis KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Animal models KW - Salivary gland KW - Interleukin 10 KW - Adeno-associated virus KW - Sjogren's syndrome KW - Gene therapy KW - Diabetes mellitus KW - b-Galactosidase KW - Gene transfer KW - ^b-Galactosidase KW - G 07444:Animal models KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19218716?accountid=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=Local+Adeno-Associated+Virus-Mediated+Interleukin+10+Gene+Transfer+Has+Disease-Modifying+Effects+in+a+Murine+Model+of+Sjoegren%27s+Syndrome&rft.au=Kok%2C+M+R%3BYamano%2C+Seichii%3BLodde%2C+B+M%3BWang%2C+Jianghua%3BCouwenhoven%2C+R+I%3BYakar%2C+S%3BVoutetakis%2C+A%3BLeroith%2C+D%3BSchmidt%2C+M%3BAfione%2C+S%3BPillemer%3BTsutsui%2C+M+T%3BTak%2C+P+P%3BChiorini%2C+JA%3BBaum%2C+B+J&rft.aulast=Kok&rft.aufirst=M&rft.date=2003-11-20&rft.volume=14&rft.issue=17&rft.spage=1605&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adeno-associated virus; Gene transfer; Gene therapy; Interleukin 10; Sjogren's syndrome; Animal models; Diabetes mellitus; Salivary gland; b-Galactosidase; ^b-Galactosidase ER - TY - JOUR T1 - Photochemical characterization of water samples from Minnesota and Vermont sites with malformed frogs: potential influence of photosensitization by singlet molecular oxygen ( super(1)O2) and free radicals on aquatic toxicity AN - 16165614; 5753277 AB - Environmental pollutants activated by UV sunlight may have contributed to the recent decline in frog populations and the concomitant increase in malformations in the USA and abroad. UV radiation is able to mutate DNA and to initiate photosensitization processes that generate mutagenic and biologically disruptive oxygen transients. We have examined water from selected sites in Minnesota and Vermont using singlet molecular oxygen ( super(1)O2), detected by its phosphorescence and free radicals detected by spin trapping, as markers for photosensitization. Water from a pond in Minnesota with malformed frogs, which also causes malformations in the laboratory, photosensitized more super(1)O2, even though it absorbed less UV light compared to water from a site that did not cause malformations. This suggested that unknown natural or pollutant agents were present, and that photosensitization may be involved. Although UV irradiation of the two Minnesota water samples in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) revealed the presence of the DMPO/OH, DMPO/H(eaq super(-)) and DMPO/C(unknown) adducts there were no qualitative or quantitative differences between them. We also examined water samples from several sites in Vermont, and compared them by measuring the quantum yield of super(1)O2 photosensitization. While all the Vermont samples produced a small amount of super(1)O2, there was no clear correlation with the incidence of frog malformations. However, the samples differed strongly in absorption spectra and the ability to quench super(1)O2. These factors may determine how much UV light is absorbed and converted into chemical reactions. Our results show that photochemical characterization of super(1)O2 photosensitization is possible in untreated natural water samples. Photosensitization falls into the category of global factors that may be closely associated with the effects of UV irradiation of the Earth's environments. Thus, photosensitization might be an important component in global amphibian malformation and decline. The observation of super(1)O2 emission directly from natural water may also provide new opportunities to investigate the involvement of super(1)O2 in other complex environmental processes. JF - Aquatic Toxicology AU - Bilski, P AU - Burkhart, J G AU - Chignell, C F AD - Laboratory of Pharmacology and Chemistry and Laboratory of Toxicology, ETP, NIEHS, Research Triangle Park, NC 27709, USA, bilski@niehs.nih.gov Y1 - 2003/11/19/ PY - 2003 DA - 2003 Nov 19 SP - 229 EP - 241 PB - Elsevier B.V. VL - 65 IS - 3 SN - 0166-445X, 0166-445X KW - Amphibians KW - True frogs KW - USA, Minnesota KW - USA, Vermont KW - oxygen radicals KW - Toxicology Abstracts; Pollution Abstracts; Water Resources Abstracts; Aqualine Abstracts KW - Photochemistry KW - Water sampling KW - Water Analysis KW - Pollution effects KW - Rana KW - Ecological Effects KW - Water KW - Malformations KW - Photosensitization KW - Frogs KW - Radiation KW - Ultraviolet radiation KW - Animal Physiology KW - Photoactivation KW - Toxicology KW - Experimental Data KW - Amphibians (Frogs) KW - Mutagenicity KW - Free radicals KW - Water pollution KW - Ultraviolet Radiation KW - Amphibia KW - Oxygen KW - Water Pollution Effects KW - Irradiation KW - Morphology KW - X 24240:Miscellaneous KW - AQ 00008:Effects of Pollution KW - SW 3030:Effects of pollution KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16165614?accountid=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=Aquatic+Toxicology&rft.atitle=Photochemical+characterization+of+water+samples+from+Minnesota+and+Vermont+sites+with+malformed+frogs%3A+potential+influence+of+photosensitization+by+singlet+molecular+oxygen+%28+super%281%29O2%29+and+free+radicals+on+aquatic+toxicity&rft.au=Bilski%2C+P%3BBurkhart%2C+J+G%3BChignell%2C+C+F&rft.aulast=Bilski&rft.aufirst=P&rft.date=2003-11-19&rft.volume=65&rft.issue=3&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Aquatic+Toxicology&rft.issn=0166445X&rft_id=info:doi/10.1016%2FS0166-445X%2803%2900138-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2004-01-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Malformations; Photosensitization; Free radicals; Water; Water pollution; Photochemistry; Oxygen; Mutagenicity; Water sampling; Irradiation; Ultraviolet radiation; Pollution effects; Toxicology; Amphibians (Frogs); Radiation; Water Analysis; Ultraviolet Radiation; Experimental Data; Frogs; Water Pollution Effects; Morphology; Amphibians; Animal Physiology; Photoactivation; Ecological Effects; Amphibia; Rana DO - http://dx.doi.org/10.1016/S0166-445X(03)00138-3 ER - TY - JOUR T1 - A framework for the conceptual modelling of assistive technology device outcomes. AN - 85376902; pmid-14617441 AB - A key step in planning assistive technology outcomes research is formulation of a conceptual model, specific to a particular type of device, that provides a rationale for the expected outcomes. This paper reflects the conviction that the development of device-specific causal models will be facilitated by having available an overarching framework that is potentially applicable to multifarious types of devices and their outcomes.A literature review identified the critical, unmet needs for a conceptual framework. The assumptions underlying the framework were specified preparatory to describing it and discussing its implications.The outcomes of assistive technology devices are depicted as resulting from the interaction among characteristics of a specific device-type, its users, and their environment. Initial junctures include procurement of a type of device and a period of introductory use that, interacting with various moderating co-factors, result in a variety of shorter-term outcomes, possible longer-term use, and its outcomes.The framework has the potential of facilitating the development of device-specific causal models. It also may contribute to developing a research agenda for assistive technology outcomes research by highlighting measures that need to be developed and by identifying testable hypotheses concerned, for example, with the manner and duration of devices' usage. JF - Disability and rehabilitation AU - Fuhrer, M J AU - Jutai, J W AU - Scherer, M J AU - DeRuyter, F AD - National Institute of Child Health and Human Development, National Institutes of Health, Damascus, MD 20872, USA. fuhrerm@mail.nih.gov Y1 - 2003/11/18/ PY - 2003 DA - 2003 Nov 18 SP - 1243 EP - 1251 VL - 25 IS - 22 SN - 0963-8288, 0963-8288 KW - Index Medicus KW - National Library of Medicine KW - Disabled Persons: rehabilitation KW - Humans KW - *Models, Theoretical KW - Needs Assessment KW - *Outcome Assessment (Health Care) KW - *Self-Help Devices KW - *Technology Assessment, Biomedical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85376902?accountid=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=A+framework+for+the+conceptual+modelling+of+assistive+technology+device+outcomes.&rft.au=Fuhrer%2C+M+J%3BJutai%2C+J+W%3BScherer%2C+M+J%3BDeRuyter%2C+F&rft.aulast=Fuhrer&rft.aufirst=M&rft.date=2003-11-18&rft.volume=25&rft.issue=22&rft.spage=1243&rft.isbn=&rft.btitle=&rft.title=Disability+and+rehabilitation&rft.issn=09638288&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - High-Resolution Structure of the Yersinia pestis Protein Tyrosine Phosphatase YopH in Complex with a Phosphotyrosyl Mimetic-Containing Hexapeptide AN - 17965573; 5914319 AB - Yersinia pestis, the causative agent of bubonic plague, secretes a eukaryotic-like protein tyrosine phosphatase (PTPase) termed Yersinia outer protein H (YopH) that is essential for virulence. We have determined, for the first time, the crystal structure of the YopH PTPase domain in complex with a nonhydrolyzable substrate analogue, the hexapeptide mimetic Ac-DADE-F sub(2)Pmp-L-NH sub(2). As anticipated, the mode of ligand binding in the active site is similar to the way in which the corresponding phosphohexapeptide binds to the structurally homologous human PTP1B. Unexpectedly, however, the crystal structure also revealed a second substrate-binding site in YopH that is not present in PTP1B. The mode of binding and structural conformation of the hexapeptide analogue is quite different in the two sites. Although the biological function of the second substrate-binding site remains to be investigated, the structure of a substrate analogue in the active site of Y. pestis YopH opens the door for the structure-based design and optimization of therapeutic countermeasures to combat this potential agent of bioterrorism. JF - Biochemistry (Washington) AU - Phan, J AU - Lee, Kyeong AU - Cherry, S AU - Tropea, JE AU - Burke, TR Jr AU - Waugh, D S AD - Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA Y1 - 2003/11/18/ PY - 2003 DA - 2003 Nov 18 SP - 13113 EP - 13121 VL - 42 IS - 45 SN - 0006-2960, 0006-2960 KW - Microbiology Abstracts B: Bacteriology KW - Virulence KW - double prime H protein KW - bioterrorism KW - Crystal structure KW - Yersinia pestis KW - protein H KW - Plague KW - Protein-tyrosine-phosphatase KW - Conformation KW - J 02728:Enzymes KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17965573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=High-Resolution+Structure+of+the+Yersinia+pestis+Protein+Tyrosine+Phosphatase+YopH+in+Complex+with+a+Phosphotyrosyl+Mimetic-Containing+Hexapeptide&rft.au=Phan%2C+J%3BLee%2C+Kyeong%3BCherry%2C+S%3BTropea%2C+JE%3BBurke%2C+TR+Jr%3BWaugh%2C+D+S&rft.aulast=Phan&rft.aufirst=J&rft.date=2003-11-18&rft.volume=42&rft.issue=45&rft.spage=13113&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi030156m LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Virulence; double prime H protein; bioterrorism; Crystal structure; protein H; Plague; Conformation; Protein-tyrosine-phosphatase; Yersinia pestis DO - http://dx.doi.org/10.1021/bi030156m ER - TY - JOUR T1 - In vitro affinity maturation of a specificity-determining region-grafted humanized anticarcinoma antibody: isolation and characterization of minimally immunogenic high-affinity variants. AN - 71464559; 14654532 AB - HuCC49V10 (V10), a humanized anticarcinoma monoclonal antibody (Ab) CC49, was generated by grafting only the specificity-determining regions (SDRs) of CC49 onto the variable light and variable heavy frameworks of the human Abs LEN and 21/28'CL, respectively. SDRs are those residues of the complementarity-determining regions that are most critical for antigen (Ag) binding. Compared with HuCC49, which was developed by conventional complementarity-determining region grafting, V10 has lower reactivity to the sera from patients who were previously given murine CC49 in clinical trials, although its Ag-binding affinity is 2-3-fold lower than that of HuCC49. To generate variants of V10 with higher Ag-binding affinity and lower sera reactivity, in vitro affinity maturation of V10 was carried out using phage display technique. A limited library of Fabs was generated by replacing some of the SDRs with all possible residues located at the corresponding positions in human Abs. The library was enriched, by several rounds of panning, in Fabs that have high affinity for the TAG-72 Ag. The clones encoding the best binders were expressed in insect cells as whole Abs that were purified and characterized. Competition radioimmunoassay and surface plasmon resonance measurements showed that two of the isolates, V14 and V15, have higher binding affinity than that of V10. In addition, the surface plasmon resonance analysis showed that the variants V14 and V15, compared with the parental V10, have lower reactivity to the anti-V region Abs using sera from patients who received murine CC49. The two isolates, V14 and V15, which show higher Ag-binding reactivity and lower sera reactivity than the parental V10 Ab, are potentially more useful clinical reagents. These results demonstrate that phage display can be used to isolate variants of an Ab that are potentially less immunogenic in patients than the parental Ab from which they are derived. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - De Pascalis, Roberto AU - Gonzales, Noreen R AU - Padlan, Eduardo A AU - Schuck, Peter AU - Batra, Surinder K AU - Schlom, Jeffrey AU - Kashmiri, Syed V S AD - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2003/11/15/ PY - 2003 DA - 2003 Nov 15 SP - 5521 EP - 5531 VL - 9 IS - 15 SN - 1078-0432, 1078-0432 KW - Antibodies, Neoplasm KW - 0 KW - Antigen-Antibody Complex KW - Antineoplastic Agents KW - B72.3 antibody KW - DNA Primers KW - Immunoglobulin Fab Fragments KW - Immunoglobulin Variable Region KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Humans KW - Immunoglobulin Variable Region -- immunology KW - Immunoglobulin Fab Fragments -- immunology KW - Drug Design KW - Amino Acid Substitution KW - Structure-Activity Relationship KW - Gene Amplification KW - Antineoplastic Agents -- immunology KW - Antibodies, Neoplasm -- pharmacology KW - Antibodies, Neoplasm -- therapeutic use KW - Antibodies, Neoplasm -- immunology KW - Adenocarcinoma -- immunology KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71464559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+vitro+affinity+maturation+of+a+specificity-determining+region-grafted+humanized+anticarcinoma+antibody%3A+isolation+and+characterization+of+minimally+immunogenic+high-affinity+variants.&rft.au=De+Pascalis%2C+Roberto%3BGonzales%2C+Noreen+R%3BPadlan%2C+Eduardo+A%3BSchuck%2C+Peter%3BBatra%2C+Surinder+K%3BSchlom%2C+Jeffrey%3BKashmiri%2C+Syed+V+S&rft.aulast=De+Pascalis&rft.aufirst=Roberto&rft.date=2003-11-15&rft.volume=9&rft.issue=15&rft.spage=5521&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 - 2004-08-17 N1 - Date created - 2003-12-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smad7 but not Smad6 cooperates with oncogenic ras to cause malignant conversion in a mouse model for squamous cell carcinoma. AN - 71385625; 14633701 AB - Smad7 and Smad6 are inhibitory Smads that block transforming growth factor-beta (TGF-beta) superfamily signal transduction. Smad7 is overexpressed in chemically induced mouse epidermal tumors, where oncogenic activation of c-ras is a frequent event. To test the role of Smad7 overexpression in tumor progression, we used retroviruses to transduce Smad7 or Smad6 and v-ras(Ha) into primary mouse keratinocytes. By itself, Smad7 transiently enhanced keratinocyte proliferation, blocked normal differentiation, and induced keratin 8, a marker of malignant conversion, but did not cause tumor formation. Smad7 extended the in vitro life span, suppressed senescence, and increased transformation frequency 3-fold of primary keratinocytes coexpressing v-ras(Ha). Smad7/v-ras(Ha) coinfected keratinocytes rapidly progressed to squamous cell carcinomas in vivo, whereas pBabe/v-ras(Ha)- or Smad6/v-ras(Ha)-transduced keratinocytes formed only benign papillomas. Smad7/v-ras(Ha) tumors had elevated proliferation and defective nuclear localizaton of Smad2, Smad3, and Smad5, whereas only Smad5 was altered in Smad6/v-ras(Ha) tumors. Smad7 overexpression in vitro induced epidermal growth factor (EGF)-like growth factors TGF-alpha, heparin binding-EGF, amphiregulin, and EGF receptor tyrosine phosphorylation as well as the EGF-CFC growth factor cripto-1. TGF-alpha and cripto-1 were also overexpressed in Smad7/v-ras(Ha) tumors. These results suggest that Smad7 overexpression accelerates tumor progression through inhibition of TGF-beta superfamily signaling and up-regulation of the EGF-like superfamily of growth factors. This is the first demonstration that Smad7 overexpression can cause malignant conversion in a multistage cancer model and suggests that it may have an important role in the pathogenesis of human cancer. JF - Cancer research AU - Liu, Xin AU - Lee, Jennifer AU - Cooley, Margaret AU - Bhogte, Ervind AU - Hartley, Stephan AU - Glick, Adam AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute/NIH, Building 37, Bethesda, MD 20892, USA. Y1 - 2003/11/15/ PY - 2003 DA - 2003 Nov 15 SP - 7760 EP - 7768 VL - 63 IS - 22 SN - 0008-5472, 0008-5472 KW - DNA-Binding Proteins KW - 0 KW - Smad6 Protein KW - Smad6 protein, mouse KW - Smad7 Protein KW - Smad7 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Papilloma -- pathology KW - Transduction, Genetic KW - Cell Division -- physiology KW - Disease Models, Animal KW - Mice KW - Mice, Nude KW - Mice, Inbred BALB C KW - Papilloma -- genetics KW - NIH 3T3 Cells KW - Transforming Growth Factor beta -- antagonists & inhibitors KW - Signal Transduction -- physiology KW - Transforming Growth Factor beta -- physiology KW - Cell Differentiation -- physiology KW - Cells, Cultured KW - Keratinocytes -- pathology KW - Up-Regulation KW - Retroviridae -- genetics KW - Cell Transformation, Neoplastic -- pathology KW - Trans-Activators -- biosynthesis KW - Trans-Activators -- genetics KW - Carcinoma, Squamous Cell -- pathology KW - Genes, ras -- physiology KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- biosynthesis KW - Carcinoma, Squamous Cell -- genetics KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71385625?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Smad7+but+not+Smad6+cooperates+with+oncogenic+ras+to+cause+malignant+conversion+in+a+mouse+model+for+squamous+cell+carcinoma.&rft.au=Liu%2C+Xin%3BLee%2C+Jennifer%3BCooley%2C+Margaret%3BBhogte%2C+Ervind%3BHartley%2C+Stephan%3BGlick%2C+Adam&rft.aulast=Liu&rft.aufirst=Xin&rft.date=2003-11-15&rft.volume=63&rft.issue=22&rft.spage=7760&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 - 2004-02-09 N1 - Date created - 2003-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-15 and IL-2 oppositely regulate expression of the chemokine receptor CX3CR1. AN - 71359959; 12881312 AB - The chemokine receptor CX3CR1 (CX3C chemokine receptor 1) is expressed in mouse blood on natural killer (NK) cells and on monocytes. Because interleukin-15 (IL-15) is an essential cytokine for NK cell development and maintenance, we hypothesized that it may induce CX3CR1 expression on this cell type. In contrast, we found that in primary mouse bone marrow-derived NK cells IL-15 specifically inhibited CX3CR1 protein and mRNA accumulation, whereas the related cytokine IL-2 did not inhibit but instead increased CX3CR1 expression. Consistent with this finding, intravenous injection of a single dose of recombinant IL-15 into C57BL/6 mice decreased steady-state CX3CR1 levels 24 hours after injection in freshly isolated peripheral blood mononuclear cells (PBMCs), splenocytes, and bone marrow cells, and treatment of mouse PBMCs with IL-15 in vitro inhibited CX3CL1 (ligand for CX3CR1)-induced chemotaxis. These data suggest that IL-15 may be a negative regulator of innate immunity by inhibiting CX3CR1 expression. These data also suggest that IL-15 inhibition of CX3CR1 may subvert potential cell immunotherapy strategies in which IL-15 is used to expand NK cell populations in vivo or ex vivo. Finally, our results provide additional evidence for differential signaling by IL-2 and IL-15, despite usage of common beta gamma c receptor chains. JF - Blood AU - Barlic, Jana AU - Sechler, Joan M AU - Murphy, Philip M AD - molecualr Signalling Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/11/15/ PY - 2003 DA - 2003 Nov 15 SP - 3494 EP - 3503 VL - 102 IS - 10 SN - 0006-4971, 0006-4971 KW - Cx3cr1 protein, mouse KW - 0 KW - Interleukin-15 KW - Interleukin-2 KW - RNA, Messenger KW - Receptors, Chemokine KW - Abridged Index Medicus KW - Index Medicus KW - Bone Marrow Cells -- metabolism KW - Blood Cells -- metabolism KW - Animals KW - Spleen -- cytology KW - Humans KW - Leukocytes, Mononuclear -- metabolism KW - RNA, Messenger -- analysis KW - Mice, Inbred C57BL KW - Mice KW - Chemotaxis -- drug effects KW - Drug Antagonism KW - Killer Cells, Natural -- metabolism KW - Female KW - Receptors, Chemokine -- biosynthesis KW - Receptors, Chemokine -- analysis KW - Interleukin-2 -- pharmacology KW - Interleukin-15 -- pharmacology KW - Receptors, Chemokine -- genetics KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71359959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=IL-15+and+IL-2+oppositely+regulate+expression+of+the+chemokine+receptor+CX3CR1.&rft.au=Barlic%2C+Jana%3BSechler%2C+Joan+M%3BMurphy%2C+Philip+M&rft.aulast=Barlic&rft.aufirst=Jana&rft.date=2003-11-15&rft.volume=102&rft.issue=10&rft.spage=3494&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-05 N1 - Date created - 2003-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia. AN - 71359907; 12881307 AB - In contrast to severe aplastic anemia (sAA), the appropriate management of patients with moderate pancytopenia is unclear. In this study, we examined the efficacy of a humanized monoclonal antibody recognizing interleukin-2 receptor (daclizumab), which has proven to be a successful immunosuppressive agent in solid organ and bone marrow transplantation. We treated 17 patients with moderate aplastic anemia (mAA) with 1 mg/kg every 2 weeks for 3 months. mAA was defined as depression of 2 of the 3 blood counts: absolute neutrophil count 1200/mm3 or less, platelet count 70,000/mm3 or less, hemoglobin level 8.5 g/dL or lower, and absolute reticulocyte count 60,000/mm3 or less. The primary end point of our protocol was a hematologic response in at least one affected peripheral blood value. Daclizumab had little toxicity. Six of the 16 (38%) evaluable patients responded to treatment. Two patients with previously chronic disease showed complete return of normal counts, which were sustained for more than 2 years following treatment. Four patients had single-lineage responses. Two previously transfusion-dependent patients became transfusion independent; one patient with many neutropenia-related infections had a normal neutrophil count following treatment. Daclizumab appears safe; its efficacy in this pilot protocol suggests that expanded study of this monoclonal antibody in immune-mediated bone marrow failure syndrome is warranted. JF - Blood AU - Maciejewski, Jaroslaw P AU - Sloand, Elaine M AU - Nunez, Olga AU - Boss, Carol AU - Young, Neal S AD - Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2003/11/15/ PY - 2003 DA - 2003 Nov 15 SP - 3584 EP - 3586 VL - 102 IS - 10 SN - 0006-4971, 0006-4971 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Humanized KW - Immunoglobulin G KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - daclizumab KW - CUJ2MVI71Y KW - Abridged Index Medicus KW - Index Medicus KW - Recombinant Proteins -- pharmacology KW - Humans KW - Child KW - Pilot Projects KW - Blood Cell Count KW - Receptors, Interleukin-2 -- immunology KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Adolescent KW - Time Factors KW - Recombinant Proteins -- therapeutic use KW - Female KW - Male KW - Immunoglobulin G -- administration & dosage KW - Anemia, Aplastic -- drug therapy KW - Immunoglobulin G -- pharmacology KW - Antibodies, Monoclonal -- pharmacology KW - Immunoglobulin G -- therapeutic use KW - Antibodies, Monoclonal -- administration & dosage KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71359907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recombinant+humanized+anti-IL-2+receptor+antibody+%28daclizumab%29+produces+responses+in+patients+with+moderate+aplastic+anemia.&rft.au=Maciejewski%2C+Jaroslaw+P%3BSloand%2C+Elaine+M%3BNunez%2C+Olga%3BBoss%2C+Carol%3BYoung%2C+Neal+S&rft.aulast=Maciejewski&rft.aufirst=Jaroslaw&rft.date=2003-11-15&rft.volume=102&rft.issue=10&rft.spage=3584&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-05 N1 - Date created - 2003-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase and glutathione S-transferase M1 polymorphisms and childhood asthma. AN - 71355366; 12969868 AB - Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) M1 are phase II enzymes important in response to oxidative stress, such as occurs during exposure to ozone. We examined the relationship between functionally significant polymorphisms in NQO1 (Pro187Ser) and GSTM1 (homozygous deletion) and asthma risk in children with high lifetime exposure to ozone. We enrolled children with asthma from the allergy referral clinic at a public pediatric hospital in Mexico City, together with their parents. We assayed for the Pro187Ser polymorphism in NQO1 using a polymerase chain reaction-restriction fragment length polymorphism assay and for the presence of GSTM1 by polymerase chain reaction among 218 case-parent triads. We did not find strong evidence of an association between NQO1 genotype alone and asthma risk. However, among subjects with homozygous deletion of GSTM1, carriers of a serine allele were at significantly reduced risk of asthma compared with Pro/Pro homozygotes (relative risk = 0.4; 95% confidence interval, 0.2-0.8). The p value for difference in relative risk for NQO1 by GSTM1 genotype = 0.013. These data are consistent with a protective effect of the NQO1 Ser allele in this population of GSTM1-null children with high ozone exposure. JF - American journal of respiratory and critical care medicine AU - David, Gloria L AU - Romieu, Isabelle AU - Sienra-Monge, Juan Jose AU - Collins, William J AU - Ramirez-Aguilar, Matiana AU - del Rio-Navarro, Blanca Estela AU - Reyes-Ruiz, Norma Isabel AU - Morris, Richard W AU - Marzec, Jacqueline M AU - London, Stephanie J AD - National Institute of Environmental Health Sciences, PO Box 12233, MD D2-01, Research Triangle Park, NC 27709, USA. davidbe1@niehs.nih.gov Y1 - 2003/11/15/ PY - 2003 DA - 2003 Nov 15 SP - 1199 EP - 1204 VL - 168 IS - 10 SN - 1073-449X, 1073-449X KW - Oxidants, Photochemical KW - 0 KW - NADP KW - 53-59-8 KW - Ozone KW - 66H7ZZK23N KW - NAD(P)H Dehydrogenase (Quinone) KW - EC 1.6.5.2 KW - NQO1 protein, human KW - Glutathione Transferase KW - EC 2.5.1.18 KW - glutathione S-transferase M1 KW - Abridged Index Medicus KW - Index Medicus KW - Oxidants, Photochemical -- adverse effects KW - Genetic Predisposition to Disease -- genetics KW - Humans KW - Child KW - Adolescent KW - Male KW - Female KW - Risk Assessment KW - Ozone -- adverse effects KW - Child, Preschool KW - NAD(P)H Dehydrogenase (Quinone) -- genetics KW - Polymorphism, Restriction Fragment Length KW - Asthma -- genetics KW - NADP -- genetics KW - Glutathione Transferase -- genetics KW - Loss of Heterozygosity -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71355366?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+and+critical+care+medicine&rft.atitle=Nicotinamide+adenine+dinucleotide+%28phosphate%29+reduced%3Aquinone+oxidoreductase+and+glutathione+S-transferase+M1+polymorphisms+and+childhood+asthma.&rft.au=David%2C+Gloria+L%3BRomieu%2C+Isabelle%3BSienra-Monge%2C+Juan+Jose%3BCollins%2C+William+J%3BRamirez-Aguilar%2C+Matiana%3Bdel+Rio-Navarro%2C+Blanca+Estela%3BReyes-Ruiz%2C+Norma+Isabel%3BMorris%2C+Richard+W%3BMarzec%2C+Jacqueline+M%3BLondon%2C+Stephanie+J&rft.aulast=David&rft.aufirst=Gloria&rft.date=2003-11-15&rft.volume=168&rft.issue=10&rft.spage=1199&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+and+critical+care+medicine&rft.issn=1073449X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-23 N1 - Date created - 2003-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tempol-H inhibits opacification of lenses in organ culture. AN - 71350701; 14607518 AB - Cataract is the world's leading cause of blindness and a disease for which no efficacious medical therapy is available. To screen potential anti-cataract agents, a lens organ culture model system was used. Opacification of lenses maintained in culture was induced by specific insults including H(2)O(2) or the cataractogenic sugar xylose. Potential anti-cataract agents were added to the culture medium and their ability to inhibit opacification and certain biochemical changes associated with the opacification were assessed. Among the compounds tested, Tempol-H, the hydroxylamine of the nitroxide Tempol, gave the most promising results. It significantly inhibited opacification of rat lenses in an H(2)O(2)-induced cataract system as well as opacification of rhesus monkey lenses induced by xylose. Tempol-H inhibited the loss of glutathione, the leakage of protein, and decreases in the ability of cultured lenses to accumulate (3)H-choline from the medium, all of which were associated with the development of lens opacification. The antioxidative activity of Tempol-H and its ability to re-dox cycle make it an attractive candidate as a therapeutic agent for the prevention of aging-related cataract. JF - Free radical biology & medicine AU - Zigler, J Samuel AU - Qin, Chuan AU - Kamiya, Toshikazu AU - Krishna, Murali C AU - Cheng, Qiufang AU - Tumminia, Santa AU - Russell, Paul AD - Laboratory of Mechanisms of Ocular Diseases, National Eye Institute, Bethesda, MD, USA. ziglers@nei.nih.gov Y1 - 2003/11/15/ PY - 2003 DA - 2003 Nov 15 SP - 1194 EP - 1202 VL - 35 IS - 10 SN - 0891-5849, 0891-5849 KW - Cyclic N-Oxides KW - 0 KW - Oxidants KW - Spin Labels KW - Xylose KW - A1TA934AKO KW - Hydrogen Peroxide KW - BBX060AN9V KW - Glutathione KW - GAN16C9B8O KW - Choline KW - N91BDP6H0X KW - tempol KW - U78ZX2F65X KW - Index Medicus KW - Animals KW - Xylose -- toxicity KW - Glutathione -- metabolism KW - Choline -- metabolism KW - Hydrogen Peroxide -- toxicity KW - Oxidation-Reduction KW - Rats KW - Rats, Sprague-Dawley KW - Cattle KW - Oxidants -- toxicity KW - Macaca mulatta KW - Organ Culture Techniques KW - Female KW - Male KW - Cyclic N-Oxides -- therapeutic use KW - Cataract -- metabolism KW - Lens, Crystalline -- metabolism KW - Lens, Crystalline -- drug effects KW - Cataract -- prevention & control KW - Cataract -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71350701?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Tempol-H+inhibits+opacification+of+lenses+in+organ+culture.&rft.au=Zigler%2C+J+Samuel%3BQin%2C+Chuan%3BKamiya%2C+Toshikazu%3BKrishna%2C+Murali+C%3BCheng%2C+Qiufang%3BTumminia%2C+Santa%3BRussell%2C+Paul&rft.aulast=Zigler&rft.aufirst=J&rft.date=2003-11-15&rft.volume=35&rft.issue=10&rft.spage=1194&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-06 N1 - Date created - 2003-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Residential magnetic field exposure and breast cancer risk: a nested case-control study from a multiethnic cohort in Los Angeles County, California. AN - 71348717; 14607805 AB - Some experimental and epidemiologic evidence suggests that residential exposure to power-frequency magnetic fields can increase breast cancer risk. This association was investigated in a nested case-control study of female breast cancer within a cohort of African Americans, Latinas, and Caucasians in Los Angeles County, California. Incident breast cancer was ascertained from 1993 to 1999 by linkage to county and state tumor registries. Controls were selected from a random sample of cohort members without breast cancer at baseline. Exposure was assessed in 1995-2001 by means of wiring configuration coding (an indirect measure of magnetic field exposure that has been associated with increased risk of childhood leukemia in Los Angeles and elsewhere in North America) in all homes occupied over the previous 10 years for 743 cases and 699 controls and by measurement of magnetic fields in the bedroom over a 7-day period for 347 cases and 286 controls. The estimated risk of breast cancer was not higher among women with wiring configuration codes associated with the highest magnetic fields (for a very high current configuration relative to very low, the adjusted odds ratio was 0.76 (95% confidence interval: 0.49, 1.18)). Stronger measured fields were not significantly associated with increased risk. These data suggest that residential magnetic field exposures commonly experienced by US women do not influence risk of breast cancer. JF - American journal of epidemiology AU - London, Stephanie J AU - Pogoda, Janice M AU - Hwang, Katherine Liao AU - Langholz, Bryan AU - Monroe, Kristine R AU - Kolonel, Laurence N AU - Kaune, William T AU - Peters, John M AU - Henderson, Brian E AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. london2@niehs.nih.gov Y1 - 2003/11/15/ PY - 2003 DA - 2003 Nov 15 SP - 969 EP - 980 VL - 158 IS - 10 SN - 0002-9262, 0002-9262 KW - Index Medicus KW - Housing -- statistics & numerical data KW - Los Angeles -- epidemiology KW - Humans KW - African Americans -- statistics & numerical data KW - Aged KW - European Continental Ancestry Group -- statistics & numerical data KW - Residence Characteristics -- statistics & numerical data KW - Selection Bias KW - Population Surveillance KW - Environmental Monitoring KW - Hispanic Americans -- statistics & numerical data KW - Postmenopause KW - Logistic Models KW - Electric Wiring -- statistics & numerical data KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Epidemiological Monitoring KW - Female KW - Breast Neoplasms -- ethnology KW - Environmental Exposure -- analysis KW - Electromagnetic Fields -- adverse effects KW - Breast Neoplasms -- etiology KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71348717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Residential+magnetic+field+exposure+and+breast+cancer+risk%3A+a+nested+case-control+study+from+a+multiethnic+cohort+in+Los+Angeles+County%2C+California.&rft.au=London%2C+Stephanie+J%3BPogoda%2C+Janice+M%3BHwang%2C+Katherine+Liao%3BLangholz%2C+Bryan%3BMonroe%2C+Kristine+R%3BKolonel%2C+Laurence+N%3BKaune%2C+William+T%3BPeters%2C+John+M%3BHenderson%2C+Brian+E&rft.aulast=London&rft.aufirst=Stephanie&rft.date=2003-11-15&rft.volume=158&rft.issue=10&rft.spage=969&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 - 2003-12-02 N1 - Date created - 2003-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RING finger 1 mutations in Parkin produce altered localization of the protein. AN - 71318454; 14519684 AB - The Parkin gene (PRKN) encodes an E3 protein-ubiquitin ligase for which loss of function is associated with autosomal-recessive juvenile (<20 years) and early-onset Parkinsonism (<45 years). Although detailed pathological reports are scarce, brains from patients with homozygous exonic deletions demonstrate neuronal loss in the substantia nigra, albeit without the Lewy body pathology characteristic of idiopathic Parkinson's disease. However, there are rare descriptions of more florid pathology, including Lewy bodies and tau positive astrocytes in individuals with compound heterozygous mutations. In the present study we examined whether PRKN point mutations, leading to amino acid substitutions, may alter the cellular distribution of the protein produced. Wild-type Parkin was homogeneously distributed throughout the cytoplasm with a small amount of protein in the nucleus after transfection into human embryonic kidney cells. Mutant isoforms with A82E, G328E and C431F amino acid substitutions were also normally distributed. However, two mutant isoforms, R256C and R275W, within RING finger 1 of the Parkin protein (238-293 amino acids), produced an unusual distribution of the protein, with large cytoplasmic and nuclear inclusions. We have replicated this observation in primary cultured neurons and demonstrate, by the accumulation/co-localization of cytoskeletal protein vimentin, that the inclusion bodies are aggresomes, a cellular response to misfolded protein. JF - Human molecular genetics AU - Cookson, Mark R AU - Lockhart, Paul J AU - McLendon, Chris AU - O'Farrell, Casey AU - Schlossmacher, Michael AU - Farrer, Matthew J AD - Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA. Y1 - 2003/11/15/ PY - 2003 DA - 2003 Nov 15 SP - 2957 EP - 2965 VL - 12 IS - 22 SN - 0964-6906, 0964-6906 KW - Protein Isoforms KW - 0 KW - Vimentin KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - parkin protein KW - Index Medicus KW - Vimentin -- biosynthesis KW - Protein Isoforms -- metabolism KW - Humans KW - Cell Nucleus -- chemistry KW - Amino Acid Sequence KW - Cytoplasm -- chemistry KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Protein Isoforms -- chemistry KW - Cells, Cultured KW - Hippocampus -- cytology KW - Neurons -- cytology KW - Protein Folding KW - Lewy Bodies -- metabolism KW - Protein Structure, Tertiary KW - Protein Isoforms -- genetics KW - Amino Acid Substitution KW - Cell Line KW - Ubiquitin-Protein Ligases -- chemistry KW - Zinc Fingers -- genetics KW - Ubiquitin-Protein Ligases -- genetics KW - Point Mutation KW - Ubiquitin-Protein Ligases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71318454?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Peptides&rft.atitle=Control+of+antimicrobial+peptide+synthesis+by+the+agr+quorum+sensing+system+in+Staphylococcus+epidermidis%3A+activity+of+the+lantibiotic+epidermin+is+regulated+at+the+level+of+precursor+peptide+processing&rft.au=Kies%2C+S%3BVuong%2C+C%3BHille%2C+M%3BPeschel%2C+A%3BMeyer%2C+C%3BGoetz%2C+F%3BOtto%2C+M&rft.aulast=Kies&rft.aufirst=S&rft.date=2003-03-01&rft.volume=24&rft.issue=3&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Peptides&rft.issn=01969781&rft_id=info:doi/10.1016%2FS0196-9781%2803%2900046-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-08 N1 - Date created - 2003-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of the 'reverse Cornfield inequality' to assess the sensitivity of a non-significant association to an omitted variable. AN - 71289393; 14566922 AB - Unlike randomized experimental studies, investigators do not have control over the treatment assignment in observational studies. Hence, the treated and control (non-treated) groups may have widely different distributions of unobserved covariates. Thus, if observational data are analysed as if they had arisen from a controlled study, the analyses are subject to potential bias. Sensitivity analysis is a technique for assessing whether the inference drawn from a study could be altered by a moderate 'imbalance', between the distribution of the covariates in different groups. In this paper, we examine the sensitivity analysis of the test of proportions in 2 x 2 tables from a new perspective: 'could a non-significant result have occurred because the treated group has a higher prevalence of an unobserved risk factor?'. The study was motivated by an analysis of the studies concerning with the possible effect of spermicide use on birth defects that were cited in a legal decision. Copyright 2003 John Wiley & Sons, Ltd. JF - Statistics in medicine AU - Yu, Binbing AU - Gastwirth, Joseph L AD - Information Management Services, Inc., 12501 Prosperity Dr. Suite 200, Silver Spring, MD 20904, USA. yu@ims.nci.nih.gov Y1 - 2003/11/15/ PY - 2003 DA - 2003 Nov 15 SP - 3383 EP - 3401 VL - 22 IS - 21 SN - 0277-6715, 0277-6715 KW - Spermatocidal Agents KW - 0 KW - Tranquilizing Agents KW - Index Medicus KW - Odds Ratio KW - Lung Neoplasms -- etiology KW - Analysis of Variance KW - Limb Deformities, Congenital -- etiology KW - Spermatocidal Agents -- adverse effects KW - Risk Factors KW - Humans KW - Case-Control Studies KW - Smoking -- adverse effects KW - Tranquilizing Agents -- adverse effects KW - Sensitivity and Specificity KW - Models, Statistical KW - Risk Assessment -- statistics & numerical data KW - Observer Variation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71289393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=The+use+of+the+%27reverse+Cornfield+inequality%27+to+assess+the+sensitivity+of+a+non-significant+association+to+an+omitted+variable.&rft.au=Yu%2C+Binbing%3BGastwirth%2C+Joseph+L&rft.aulast=Yu&rft.aufirst=Binbing&rft.date=2003-11-15&rft.volume=22&rft.issue=21&rft.spage=3383&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 completed - 2004-02-27 N1 - Date created - 2003-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alternatives to HIV-1 RNA concentration and CD4 count to predict mortality in HIV-1-infected children in resource-poor settings AN - 199090716; 14630444 AB - Cheaper, simpler alternatives to CD4 lymphocyte count and HIV-1 RNA detection for assessing the prognosis of HIV-1 infection are needed for resource-poor settings. However, little is known about the predictive value of alternative assays, in particular in children. We assessed the prognostic value of total lymphocyte count, immune complex-dissociated p24 antigen, white blood cell count, packed-cell volume (haematocrit), and serum albumin for mortality in 376 HIV-1-infected, mainly African-American or Hispanic children enrolled during March, 1988 to January, 1991. In a Cox proportional hazards model, including all assay-alternatives to CD4 and RNA, total lymphocyte count (p<0.0001) and serum albumin (p=0.0107) independently predicted mortality. Further assessment of these markers is warranted in resource-poor settings. JF - The Lancet AU - Mofenson, L M AU - Harris, D R AU - Moye, J AU - Bethel, J AU - et al Y1 - 2003/11/15/ PY - 2003 DA - 2003 Nov 15 SP - 1625 EP - 7 CY - London PB - Elsevier Limited VL - 362 IS - 9396 SN - 01406736 KW - Medical Sciences KW - Biological Markers KW - HIV Core Protein p24 KW - RNA, Viral KW - Human immunodeficiency virus--HIV KW - Ribonucleic acid--RNA KW - Children & youth KW - Infant mortality KW - Blood KW - Clinical trials KW - HIV Core Protein p24 -- blood KW - Humans KW - Infant, Newborn KW - Prognosis KW - Child KW - CD4 Lymphocyte Count KW - HIV-1 KW - Child, Preschool KW - Viral Load KW - Infant KW - Hematocrit KW - Female KW - Male KW - RNA, Viral -- blood KW - Proportional Hazards Models KW - Biological Markers -- blood KW - HIV Infections -- blood KW - HIV Infections -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/199090716?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Lancet&rft.atitle=Alternatives+to+HIV-1+RNA+concentration+and+CD4+count+to+predict+mortality+in+HIV-1-infected+children+in+resource-poor+settings&rft.au=Mofenson%2C+L+M%3BHarris%2C+D+R%3BMoye%2C+J%3BBethel%2C+J%3Bet+al&rft.aulast=Mofenson&rft.aufirst=L&rft.date=2003-11-15&rft.volume=362&rft.issue=9396&rft.spage=1625&rft.isbn=&rft.btitle=&rft.title=The+Lancet&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright Lancet Ltd. Nov 15, 2003 N1 - Last updated - 2015-02-07 N1 - CODEN - LANCAO ER - TY - JOUR T1 - Modified Vaccinia Virus Ankara Recombinants Are as Potent as Vaccinia Recombinants in Diversified Prime and Boost Vaccine Regimens to Elicit Therapeutic Antitumor Responses AN - 19238964; 5802956 AB - Cancer vaccine regimens use various strategies to enhance immune responses to specific tumor-associated antigens (TAAs), including the increasing use of recombinant poxviruses [vaccinia (rV) and fowlpox (rF)] for delivery of the TAA to the immune system. However, the use of replication competent vectors with the potential of adverse reactions have made attenuation a priority for next-generation vaccine strategies. Modified vaccinia Ankara (MVA) is a replication defective form of vaccinia virus. Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM). Vaccination of mice with MVA-CEA/TRICOM induced potent CD4 super(+) and CD8 super(+) T-cell responses specific for CEA. MVA-CEA/TRICOM could be administered twice in vaccinia naive mice and only a single time in vaccinia-immune mice before being inhibited by antivector-immune responses. The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4 super(+) and CD8 super(+) T-cell responses specific for CEA than that seen with rV-CEA/TRICOM prime and rF-CEA/TRICOM boost. In a self-antigen tumor model, the diversified MVA-CEA/TRICOM/rF-CEA/TRICOM vaccination regimen resulted in a significant therapeutic antitumor response as measured by increased survival, when compared with the diversified prime and boost regimen, rV-CEA/TRICOM/rF-CEA/TRICOM. The studies reported here demonstrate that MVA, when used as a prime in a diversified vaccination, is clearly comparable with the regimen using the recombinant vaccinia in both the induction of cellular immune responses specific for the "self"-TAA transgene and in antitumor activity. JF - Cancer Research AU - Hodge, J W AU - Poole, D J AU - Aarts, WM AU - Yafal, A G AU - Gritz, L AU - Schlom, J AD - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Y1 - 2003/11/15/ PY - 2003 DA - 2003 Nov 15 SP - 7942 EP - 7949 VL - 63 IS - 22 SN - 0008-5472, 0008-5472 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Vaccinia virus KW - Carcinoembryonic antigen KW - Antigen (tumor-associated) KW - Lymphocytes T KW - Fowlpox virus KW - CD8 antigen KW - Vaccines KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19238964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Modified+Vaccinia+Virus+Ankara+Recombinants+Are+as+Potent+as+Vaccinia+Recombinants+in+Diversified+Prime+and+Boost+Vaccine+Regimens+to+Elicit+Therapeutic+Antitumor+Responses&rft.au=Hodge%2C+J+W%3BPoole%2C+D+J%3BAarts%2C+WM%3BYafal%2C+A+G%3BGritz%2C+L%3BSchlom%2C+J&rft.aulast=Hodge&rft.aufirst=J&rft.date=2003-11-15&rft.volume=63&rft.issue=22&rft.spage=7942&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccinia virus; Fowlpox virus; Antigen (tumor-associated); Vaccines; Expression vectors; Carcinoembryonic antigen; Lymphocytes T; CD8 antigen ER - TY - JOUR T1 - Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity. AN - 71353648; 12923173 AB - The nuclear receptors, farnesoid X receptor (FXR) and pregnane X receptor (PXR), are important in maintaining bile acid homeostasis. Deletion of both FXR and PXR in vivo by cross-breeding B6;129-Fxrtm1Gonz (FXR-null) and B6;129-Pxrtm1Glaxo-Wellcome (PXR-null) mice revealed a more severe disruption of bile acid, cholesterol, and lipid homeostasis in B6;129-Fxrtm1Gonz Pxrtm1Glaxo-Wellcome (FXR-PXR double null or FPXR-null) mice fed a 1% cholic acid (CA) diet. Hepatic expression of the constitutive androstane receptor (CAR) and its target genes was induced in FXR- and FPXR-null mice fed the CA diet. To test whether up-regulation of CAR represents a means of protection against bile acid toxicity to compensate for the loss of FXR and PXR, animals were pretreated with CAR activators, phenobarbital or 1,4-bis[2-(3,5-dichlorpyridyloxy)]benzene (TCPOBOP), followed by the CA diet. A role for CAR in protection against bile acid toxicity was confirmed by a marked reduction of serum bile acid and bilirubin concentrations, with an elevation of the expression of the hepatic genes involved in bile acid and/or bilirubin metabolism and excretion (CYP2B, CYP3A, MRP2, MRP3, UGT1A, and glutathione S-transferase alpha), following pretreatment with phenobarbital or TCPOBOP. In summary, the current study demonstrates a critical and combined role of FXR and PXR in maintaining not only bile acid but also cholesterol and lipid homeostasis in vivo. Furthermore, FXR, PXR, and CAR protect against hepatic bile acid toxicity in a complementary manner, suggesting that they serve as redundant but distinct layers of defense to prevent overt hepatic damage by bile acids during cholestasis. JF - The Journal of biological chemistry AU - Guo, Grace L AU - Lambert, Gilles AU - Negishi, Masahiko AU - Ward, Jerrold M AU - Brewer, H Bryan AU - Kliewer, Steven A AU - Gonzalez, Frank J AU - Sinal, Christopher J AD - Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/11/14/ PY - 2003 DA - 2003 Nov 14 SP - 45062 EP - 45071 VL - 278 IS - 46 SN - 0021-9258, 0021-9258 KW - Bile Acids and Salts KW - 0 KW - DNA-Binding Proteins KW - MRP2 protein, S cerevisiae KW - Mitochondrial Proteins KW - Phospholipids KW - Pyridines KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Steroid KW - Ribosomal Proteins KW - Saccharomyces cerevisiae Proteins KW - Transcription Factors KW - constitutive androstane receptor KW - farnesoid X-activated receptor KW - pregnane X receptor KW - 1,4-bis(2-(3,5-dichloropyridyloxy))benzene KW - 76150-91-9 KW - Cholesterol KW - 97C5T2UQ7J KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Bilirubin KW - RFM9X3LJ49 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Cell Nucleus -- metabolism KW - Phospholipids -- metabolism KW - Glutathione Transferase -- metabolism KW - Biological Transport KW - Liver -- metabolism KW - Mice KW - Mice, Transgenic KW - Gene Deletion KW - Cloning, Molecular KW - Body Weight KW - Animal Feed KW - Aryl Hydrocarbon Hydroxylases -- metabolism KW - Ribosomal Proteins -- metabolism KW - Phenobarbital -- metabolism KW - Bilirubin -- metabolism KW - Cholesterol -- metabolism KW - Crosses, Genetic KW - Up-Regulation KW - Time Factors KW - Pyridines -- pharmacology KW - Oxidoreductases, N-Demethylating -- metabolism KW - Lipid Metabolism KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Receptors, Steroid -- physiology KW - DNA-Binding Proteins -- physiology KW - Bile Acids and Salts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71353648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Complementary+roles+of+farnesoid+X+receptor%2C+pregnane+X+receptor%2C+and+constitutive+androstane+receptor+in+protection+against+bile+acid+toxicity.&rft.au=Guo%2C+Grace+L%3BLambert%2C+Gilles%3BNegishi%2C+Masahiko%3BWard%2C+Jerrold+M%3BBrewer%2C+H+Bryan%3BKliewer%2C+Steven+A%3BGonzalez%2C+Frank+J%3BSinal%2C+Christopher+J&rft.aulast=Guo&rft.aufirst=Grace&rft.date=2003-11-14&rft.volume=278&rft.issue=46&rft.spage=45062&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 - 2003-12-24 N1 - Date created - 2003-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Basic Amino Acids in a Distinct Subset of Signal Peptides Promote Interaction with the Signal Recognition Particle AN - 18956268; 5753091 AB - Previous studies have demonstrated that signal peptides bind to the signal recognition particle (SRP) primarily via hydrophobic interactions with the 54- kDa protein subunit. The crystal structure of the conserved SRP ribonucleoprotein core, however, raised the surprising possibility that electrostatic interactions between basic amino acids in signal peptides and the phosphate backbone of SRP RNA may also play a role in signal sequence recognition. To test this possibility we examined the degree to which basic amino acids in a signal peptide influence the targeting of two Escherichia coli proteins, maltose binding protein and OmpA. Whereas both proteins are normally targeted to the inner membrane by SecB, we found that replacement of their native signal peptides with another moderately hydrophobic but unusually basic signal peptide ([Delta]EspP) rerouted them into the SRP pathway. Reduction in either the net positive charge or the hydrophobicity of the [Delta]EspP signal peptide decreased the effectiveness of SRP recognition. A high degree of hydrophobicity, however, compensated for the loss of basic residues and restored SRP binding. Taken together, the data suggest that the formation of salt bridges between SRP RNA and basic amino acids facilitates the binding of a distinct subset of signal peptides whose hydrophobicity falls slightly below a threshold level. JF - Journal of Biological Chemistry AU - Peterson, J H AU - Woolhead, CA AU - Bernstein, H D AD - Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0538, harris_bernstein@nih.gov Y1 - 2003/11/14/ PY - 2003 DA - 2003 Nov 14 SP - 46155 EP - 46162 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 278 IS - 46 SN - 0021-9258, 0021-9258 KW - OmpA protein KW - SRP protein KW - maltose-binding protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Signal recognition particle KW - Signal peptides KW - Hydrophobicity KW - Ribonucleoproteins KW - Crystal structure KW - Escherichia coli KW - N 14910:Nucleoproteins KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18956268?accountid=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=Basic+Amino+Acids+in+a+Distinct+Subset+of+Signal+Peptides+Promote+Interaction+with+the+Signal+Recognition+Particle&rft.au=Peterson%2C+J+H%3BWoolhead%2C+CA%3BBernstein%2C+H+D&rft.aulast=Peterson&rft.aufirst=J&rft.date=2003-11-14&rft.volume=278&rft.issue=46&rft.spage=46155&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M309082200 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Signal recognition particle; Crystal structure; Ribonucleoproteins; Hydrophobicity; Signal peptides DO - http://dx.doi.org/10.1074/jbc.M309082200 ER - TY - JOUR T1 - The SufE Protein and the SufBCD Complex Enhance SufS Cysteine Desulfurase Activity as Part of a Sulfur Transfer Pathway for Fe-S Cluster Assembly in Escherichia coli AN - 18956199; 5753051 AB - The sufABCDSE operon of the Gram-negative bacterium Escherichia coli is induced by oxidative stress and iron deprivation. To examine the biochemical roles of the Suf proteins, we purified all of the proteins and assayed their effect on SufS cysteine desulfurase activity. Here we report that the SufE protein can stimulate the cysteine desulfurase activity of the SufS enzyme up to 8-fold and accepts sulfane sulfur from SufS. This sulfur transfer process from SufS to SufE is sheltered from the environment based on its resistance to added reductants and on the analysis of available crystal structures of the proteins. We also found that the SufB, SufC, and SufD proteins associate in a stable complex and that, in the presence of SufE, the SufBCD complex further stimulates SufS activity up to 32-fold. Thus, the SufE protein and the SufBCD complex act synergistically to modulate the cysteine desulfurase activity of SufS. We propose that this sulfur transfer mechanism may be important for limiting sulfide release during oxidative stress conditions in vivo. JF - Journal of Biological Chemistry AU - Outten, F W AU - Wood, MJ AU - Munoz, F M AU - Storz, G AD - Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, storz@helix.nih.gov Y1 - 2003/11/14/ PY - 2003 DA - 2003 Nov 14 SP - 45713 EP - 45719 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 278 IS - 46 SN - 0021-9258, 0021-9258 KW - SufE protein KW - cysteine desulfurase KW - iron-sulfur KW - Microbiology Abstracts B: Bacteriology KW - Sulfide KW - Oxidative stress KW - Clusters KW - Escherichia coli KW - Operons KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18956199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=The+SufE+Protein+and+the+SufBCD+Complex+Enhance+SufS+Cysteine+Desulfurase+Activity+as+Part+of+a+Sulfur+Transfer+Pathway+for+Fe-S+Cluster+Assembly+in+Escherichia+coli&rft.au=Outten%2C+F+W%3BWood%2C+MJ%3BMunoz%2C+F+M%3BStorz%2C+G&rft.aulast=Outten&rft.aufirst=F&rft.date=2003-11-14&rft.volume=278&rft.issue=46&rft.spage=45713&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M308004200 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Sulfide; Clusters; Oxidative stress; Operons; Escherichia coli DO - http://dx.doi.org/10.1074/jbc.M308004200 ER - TY - JOUR T1 - 'Antiparallel' DNA Loop in Gal Repressosome Visualized by Atomic Force Microscopy AN - 18894441; 5771742 AB - DNA looping is often involved in positive and negative regulation of gene transcription in both prokaryotes and eukaryotes. The transcription of the gal operon of Escherichia coli from two overlapping promoters P1 and P2 is negatively regulated via Gal repressosome assembly. It involves binding of two dimeric Gal repressor proteins (GalR) to two operators, OE and OI, flanking the two promoters, and formation of 113 bp DNA loop due to tetramerization of the two bound GalR dimers. The process requires negatively supercoiled DNA and the presence of the histone-like protein HU. Previous modeling of the repressosome based on evaluation of DNA elastic energy suggested a mutual antiparallel, rather than parallel, orientation of the two gal operators in an under-twisted DNA loop. To visualize the Gal loop by atomic force microscopy (AFM), plasmid DNA molecules were constructed with increased distance between the two operators. The AFM results demonstrated the formation of an antiparallel DNA loop in the Gal repressosome consistent with our earlier hypothesis. Importantly, the overall shape of the GalR mediated loop proved to be indistinguishable from that in the chimerical loop of the same size containing two lac operators (instead of two gal operators) and formed by LacI. In addition, a possibility of the gal operon repression mediated by GalR in the absence of HU was shown in the new DNA constructs. Implications of these findings for the DNA structural organization in bacterial nucleoid are discussed. JF - Journal of Molecular Biology AU - Virnik, K AU - Lyubchenko, Y L AU - Karymov, MA AU - Dahlgren, P AU - Tolstorukov, MY AU - Semsey, S AU - Zhurkin, V B AU - Adhya, S AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, sadhya@helix.nih.gov Y1 - 2003/11/14/ PY - 2003 DA - 2003 Nov 14 SP - 53 EP - 63 PB - Elsevier Ltd VL - 334 IS - 1 SN - 0022-2836, 0022-2836 KW - GalR protein KW - HU protein KW - double prime HU protein KW - atomic force microscopy KW - repressosomes KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02725:DNA KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18894441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=%27Antiparallel%27+DNA+Loop+in+Gal+Repressosome+Visualized+by+Atomic+Force+Microscopy&rft.au=Virnik%2C+K%3BLyubchenko%2C+Y+L%3BKarymov%2C+MA%3BDahlgren%2C+P%3BTolstorukov%2C+MY%3BSemsey%2C+S%3BZhurkin%2C+V+B%3BAdhya%2C+S&rft.aulast=Virnik&rft.aufirst=K&rft.date=2003-11-14&rft.volume=334&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1016%2Fj.jmb.2003.09.030 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.jmb.2003.09.030 ER - TY - JOUR T1 - Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features. AN - 71358582; 14581620 AB - Diminished Sonic Hedgehog (Shh) signaling is associated with the most common forebrain defect in humans, holoprosencephaly (HPE), which includes cyclopia, a phenotype also seen in mice and other vertebrates with defective Shh signaling. The secreted protein Shh acts as a crucial factor that patterns the ventral forebrain and is required for the division of the primordial eye field and brain into two discrete halves. Gli2 is one of three vertebrate transcription factors implicated as obligatory mediators of Shh signal transduction. Here, we show that loss-of-function mutations in the human GLI2 gene are associated with a distinctive phenotype (within the HPE spectrum) whose primary features include defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and HPE-like midfacial hypoplasia. We also demonstrate that these mutations lack GLI2 activity. We report on a functional association between GLI2 and human disease and highlight the role of GLI2 in human head development. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Roessler, Erich AU - Du, Yang-Zhu AU - Mullor, Jose L AU - Casas, Esther AU - Allen, William P AU - Gillessen-Kaesbach, Gabriele AU - Roeder, Elizabeth R AU - Ming, Jeffrey E AU - Ruiz i Altaba, Ariel AU - Muenke, Maximilian AD - Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-1852, USA. Y1 - 2003/11/11/ PY - 2003 DA - 2003 Nov 11 SP - 13424 EP - 13429 VL - 100 IS - 23 SN - 0027-8424, 0027-8424 KW - DNA, Complementary KW - 0 KW - GLI2 protein, human KW - Gli2 protein KW - Kruppel-Like Transcription Factors KW - Nuclear Proteins KW - RNA, Messenger KW - Transcription Factors KW - Index Medicus KW - Phylogeny KW - Animals KW - Prosencephalon -- metabolism KW - COS Cells KW - Facies KW - DNA Mutational Analysis KW - Humans KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Skin Neoplasms -- metabolism KW - Phenotype KW - Mutagenesis, Site-Directed KW - Alleles KW - RNA, Messenger -- metabolism KW - Transfection KW - DNA, Complementary -- metabolism KW - Models, Genetic KW - Mice, Inbred C3H KW - Xenopus KW - Transcription Factors -- metabolism KW - Pituitary Gland -- abnormalities KW - Holoprosencephaly -- genetics KW - Transcription Factors -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71358582?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Loss-of-function+mutations+in+the+human+GLI2+gene+are+associated+with+pituitary+anomalies+and+holoprosencephaly-like+features.&rft.au=Roessler%2C+Erich%3BDu%2C+Yang-Zhu%3BMullor%2C+Jose+L%3BCasas%2C+Esther%3BAllen%2C+William+P%3BGillessen-Kaesbach%2C+Gabriele%3BRoeder%2C+Elizabeth+R%3BMing%2C+Jeffrey+E%3BRuiz+i+Altaba%2C+Ariel%3BMuenke%2C+Maximilian&rft.aulast=Roessler&rft.aufirst=Erich&rft.date=2003-11-11&rft.volume=100&rft.issue=23&rft.spage=13424&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 - 2004-01-05 N1 - Date created - 2003-11-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Development. 2002 Oct;129(20):4753-61 [12361967] Nat Rev Neurosci. 2002 Jan;3(1):24-33 [11823802] Development. 2003 Apr;130(8):1549-64 [12620981] Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R15-25 [12668593] Nat Genet. 1993 Mar;3(3):241-6 [8387379] Acta Anat (Basel). 1994;150(1):38-44 [7976186] Nature. 1996 Oct 3;383(6599):407-13 [8837770] Nat Genet. 1996 Nov;14(3):357-60 [8896572] Development. 1997 Apr;124(7):1313-22 [9118802] Cell. 1997 Jun 27;89(7):1043-53 [9215627] Development. 1997 Jul;124(13):2537-52 [9216996] Neuron. 1997 Jul;19(1):15-26 [9247260] Nature. 1997 Oct 23;389(6653):876-81 [9349822] Nat Genet. 1998 Oct;20(2):180-3 [9771712] Genes Dev. 1999 Feb 15;13(4):388-93 [10049354] J Biol Chem. 1999 Mar 19;274(12):8143-52 [10075717] Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2880-4 [10077605] Trends Genet. 1999 Jun;15(6):236-40 [10354584] Development. 1999 Jun;126(14):3205-16 [10375510] Development. 1999 Sep;126(17):3915-24 [10433919] Am J Hum Genet. 1999 Sep;65(3):645-55 [10441570] J Virol. 1998 May;72(5):3958-64 [9557682] Development. 1998 Jun;125(12):2203-12 [9584120] Nature. 1998 Jun 11;393(6685):579-83 [9634234] Development. 1998 Jul;125(14):2533-43 [9636069] Development. 1998 Aug;125(15):2759-70 [9655799] Development. 1998 Aug;125(15):2803-11 [9655803] Nat Genet. 1998 Sep;20(1):54-7 [9731531] Am J Med Genet. 1999 Nov 26;87(3):207-16 [10564872] Nat Genet. 2000 Mar;24(3):216-7 [10700170] Development. 2000 Apr;127(8):1593-605 [10725236] Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3438-43 [10725363] Development. 2000 Oct;127(19):4293-301 [10976059] Development. 2000 Oct;127(20):4395-405 [11003839] Nat Neurosci. 2000 Oct;3(10):979-85 [11017169] Development. 2001 Feb;128(3):377-86 [11152636] J Biol Chem. 2001 Mar 9;276(10):6889-92 [11238441] Curr Biol. 2001 May 15;11(10):769-73 [11378387] Bioessays. 2001 Oct;23(10):888-900 [11598956] Development. 2001 Dec;128(24):5161-72 [11748151] Development. 2001 Dec;128(24):5201-12 [11748155] Development. 2002 Nov;129(21):4963-74 [12397105] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a New Chondropsin Class of Antitumor Compound That Selectively Inhibits V-ATPases AN - 20234664; 5752994 AB - We identify a new naturally occurring class of inhibitor of vacuolar H super(+)- ATPases (V-ATPases) isolated from vacuolar membranes of Neurospora crassa and from chromaffin granule membranes of Bos taurus. To date, the new class includes six chondropsins and poecillastrin A, large polyketide-derived macrolide lactams with 33-37 membered rings. In the National Cancer Institute's 60-cell screen the chondropsin class showed a tumor cell growth inhibitory fingerprint essentially indistinguishable from that of the bafilomycin/concanamycin and the salicylihalamide/lobatamide classes of well-established V-ATPase inhibitors. Half-maximal inhibition of V-ATPase activity in vitro occurred at 0.04-0.7 mu M for the fungal vacuolar V-ATPase and at 0.4 to >10 mu M for the chromaffin granule V-ATPase. Thus, the new inhibitors are somewhat less potent than the other two classes, which typically have K sub(i) values of <10 nM for V-ATPases, and the new inhibitors differ from the other two classes in their specificity. The bafilomycin class inhibits all eucaryotic V-ATPases, the salicylihalamide class inhibits mammalian V-ATPases but not fungal V-ATPases, and the new chondropsin class inhibits the N. crassa V-ATPase better than the chromaffin granule V-ATPase. Two mutations in the N. crassa V-ATPase that affect the binding of bafilomycin had small but reproducible effects on the affinity of chondropsins for the V-ATPase, suggesting the possibility of a similar mechanism of inhibition. JF - Journal of Biological Chemistry AU - Bowman, E J AU - Gustafson, K R AU - Bowman, B J AU - Boyd, M R AD - Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, California 95064, the Molecular Targets Development Program, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702, rbowman@biology.ucsc.edu Y1 - 2003/11/07/ PY - 2003 DA - 2003 Nov 07 SP - 44147 EP - 44152 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 278 IS - 45 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Biotechnology and Bioengineering Abstracts KW - Neurospora crassa KW - Chromaffin granules KW - Adenosinetriphosphatase KW - Bos taurus KW - Hydrogen KW - H super(+)-transporting ATPase KW - Tumor cells KW - Mutation KW - W 30915:Pharmaceuticals & Vaccines KW - K 03320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20234664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Identification+of+a+New+Chondropsin+Class+of+Antitumor+Compound+That+Selectively+Inhibits+V-ATPases&rft.au=Bowman%2C+E+J%3BGustafson%2C+K+R%3BBowman%2C+B+J%3BBoyd%2C+M+R&rft.aulast=Bowman&rft.aufirst=E&rft.date=2003-11-07&rft.volume=278&rft.issue=45&rft.spage=44147&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M306595200 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Chromaffin granules; Adenosinetriphosphatase; Hydrogen; H super(+)-transporting ATPase; Mutation; Tumor cells; Neurospora crassa; Bos taurus DO - http://dx.doi.org/10.1074/jbc.M306595200 ER - TY - JOUR T1 - Synthesis and biological evaluation of 5-substituted derivatives of the potent antiherpes agent (north)-methanocarbathymine. AN - 71316242; 14584954 AB - The conformationally locked nucleoside, (north)-methanocarbathymine (1a), is a potent and selective anti-herpes agent effective against herpes simplex type 1 (HSV1) and type 2 (HSV2) viruses. Hereby, we report on the synthesis and biological evaluation of a small set of 5-substituted pyrimidine nucleosides belonging to the same class of bicyclo[3.1.0]hexane nucleosides. Both the 5-bromovinyl (4) and the 5-bromo analogue (3) appeared to be exclusive substrates of HSV1 thymidine kinase (TK), contrasting with the 5-iodo analogue (2), which was significantly phosphorylated by the human cytosolic TK. The binding affinity constant and catalytic turnover for HSV1 TK were measured to assess the influence of the substitution on these parameters. In the plaque reduction and cytotoxicity assays, the 5-bromo analogue (3) showed good activity against HSV1 and HSV2 with less general toxicity than 1a. Against varicella-zoster virus (VZV), the north-locked 5-bromovinyl analogue (4) proved to be as potent as its conformationally unlocked 2'-deoxyriboside equivalent BVDU. The three compounds were also tested in vitro as prodrugs used in a gene therapy context on three osteosarcoma cell lines, either deficient in TK (TK(-)), nontransduced, or stably transduced with HSV1 TK. The 5-iodo compound (2, CC(50) 25 +/- 7 microM) was more efficient than ganciclovir (GCV, CC(50) 75 +/- 35 microM) in inhibiting growth of HSV1-TK transfected cells and less inhibitory than GCV toward TK(-) cells, whereas compound 3 inhibited transfected and nontransfected cell lines in a relatively similar dose-dependent manner. JF - Journal of medicinal chemistry AU - Russ, Pamela AU - Schelling, Pierre AU - Scapozza, Leonardo AU - Folkers, Gerd AU - Clercq, Erik De AU - Marquez, Victor E AD - Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, 376 Boyles St., Frederick, Maryland 21702, USA. Y1 - 2003/11/06/ PY - 2003 DA - 2003 Nov 06 SP - 5045 EP - 5054 VL - 46 IS - 23 SN - 0022-2623, 0022-2623 KW - (north)-methanocarbathymine KW - 0 KW - Antiviral Agents KW - Pyrimidine Nucleosides KW - Thymidine Kinase KW - EC 2.7.1.21 KW - thymidine kinase 1 KW - Thymine KW - QR26YLT7LT KW - Index Medicus KW - Herpesvirus 3, Human -- growth & development KW - Herpesvirus 3, Human -- drug effects KW - Viral Plaque Assay KW - Humans KW - Cell Division -- drug effects KW - Thymidine Kinase -- chemistry KW - Cell Line, Tumor KW - Vaccinia virus -- drug effects KW - Poxviridae -- drug effects KW - Structure-Activity Relationship KW - Herpesvirus 2, Human -- growth & development KW - Herpesvirus 2, Human -- drug effects KW - Poxviridae -- growth & development KW - Vaccinia virus -- growth & development KW - Kinetics KW - Herpesvirus 1, Human -- growth & development KW - Molecular Conformation KW - Cell Line KW - Herpesvirus 1, Human -- drug effects KW - Thymine -- pharmacology KW - Thymine -- chemical synthesis KW - Thymine -- chemistry KW - Thymine -- analogs & derivatives KW - Antiviral Agents -- chemical synthesis KW - Pyrimidine Nucleosides -- chemistry KW - Antiviral Agents -- pharmacology KW - Antiviral Agents -- chemistry KW - Pyrimidine Nucleosides -- chemical synthesis KW - Pyrimidine Nucleosides -- pharmacology KW - Herpesviridae -- growth & development KW - Herpesviridae -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71316242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Synthesis+and+biological+evaluation+of+5-substituted+derivatives+of+the+potent+antiherpes+agent+%28north%29-methanocarbathymine.&rft.au=Russ%2C+Pamela%3BSchelling%2C+Pierre%3BScapozza%2C+Leonardo%3BFolkers%2C+Gerd%3BClercq%2C+Erik+De%3BMarquez%2C+Victor+E&rft.aulast=Russ&rft.aufirst=Pamela&rft.date=2003-11-06&rft.volume=46&rft.issue=23&rft.spage=5045&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 - 2003-12-19 N1 - Date created - 2003-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modeling the adenosine receptors: comparison of the binding domains of A2A agonists and antagonists. AN - 71316144; 14584936 AB - A three-dimensional model of the human A(2A) adenosine receptor (AR) and its docked ligands was built by homology to rhodopsin and validated with site-directed mutagenesis and the synthesis of chemically complementary agonists. Different binding modes of A(2A)AR antagonists and agonists were compared by using the FlexiDock automated docking procedure, with manual adjustment. Putative binding regions for the 9H-purine ring in agonist NECA 3 and the 1H-[1,2,4]triazolo[1,5-c]quinazoline ring in antagonist CGS15943 1 overlapped, and the exocyclic amino groups of each were H-bonded to the side chain of N(6.55). For bound agonist, H-bonds formed between the ribose 3'- and 5'-substituents and the hydrophilic amino acids T(3.36), S(7.42), and H(7.43), and the terminal methyl group of the 5'-uronamide interacted with the hydrophobic side chain of F(6.44). Formation of the agonist complex destabilized the ground-state structure of the A(2A)AR, which was stabilized through a network of H-bonding and hydrophobic interactions in the transmembrane helical domain (TM) regions, facilitating a conformational change upon activation. Both flexibility of the ribose moiety, required for the movement of TM6, and its H-bonding to the receptor were important for agonism. Two sets of interhelical H-bonds involved residues conserved among ARs but not in rhodopsin: (1) E13(1.39) and H278(7.43) and (2) D52(2.50), with the highly conserved amino acids N280(7.45) and S281(7.46), and N284(7.49) with S91(3.39). Most of the amino acid residues lining the putative binding site(s) were conserved among the four AR subtypes. The A(2A)AR/3 complex showed a preference for an intermediate conformation about the glycosidic bond, unlike in the A(3)AR/3 complex, which featured an anti-conformation. Hydrophilic amino acids of TMs 3 and 7 (ribose-binding region) were replaced with anionic residues for enhanced binding to amine-derivatized agonists. We identified new neoceptor (T88D)-neoligand pairs that were consistent with the model. JF - Journal of medicinal chemistry AU - Kim, Soo-Kyung AU - Gao, Zhan-Guo AU - Van Rompaey, Philippe AU - Gross, Ariel S AU - Chen, Aishe AU - Van Calenbergh, Serge AU - Jacobson, Kenneth A AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA. Y1 - 2003/11/06/ PY - 2003 DA - 2003 Nov 06 SP - 4847 EP - 4859 VL - 46 IS - 23 SN - 0022-2623, 0022-2623 KW - Adenosine A2 Receptor Agonists KW - 0 KW - Adenosine A2 Receptor Antagonists KW - Ligands KW - Quinazolines KW - Receptors, Adenosine A2 KW - Triazoles KW - 9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine KW - 104615-18-1 KW - Adenosine-5'-(N-ethylcarboxamide) KW - 35920-39-9 KW - Index Medicus KW - Animals KW - Hydrophobic and Hydrophilic Interactions KW - Adenosine-5'-(N-ethylcarboxamide) -- chemistry KW - COS Cells KW - Quinazolines -- chemistry KW - Models, Molecular KW - Adenosine-5'-(N-ethylcarboxamide) -- pharmacology KW - Humans KW - Triazoles -- chemistry KW - Triazoles -- pharmacology KW - Radioligand Assay KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Receptors, Adenosine A2 -- genetics KW - Hydrogen Bonding KW - Quinazolines -- pharmacology KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71316144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modeling+the+adenosine+receptors%3A+comparison+of+the+binding+domains+of+A2A+agonists+and+antagonists.&rft.au=Kim%2C+Soo-Kyung%3BGao%2C+Zhan-Guo%3BVan+Rompaey%2C+Philippe%3BGross%2C+Ariel+S%3BChen%2C+Aishe%3BVan+Calenbergh%2C+Serge%3BJacobson%2C+Kenneth+A&rft.aulast=Kim&rft.aufirst=Soo-Kyung&rft.date=2003-11-06&rft.volume=46&rft.issue=23&rft.spage=4847&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 - 2003-12-19 N1 - Date created - 2003-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries. AN - 71346246; 14600094 AB - Many U.S. factory workers are exposed to formaldehyde. Although increased risks for leukemia have been found in medical workers and other professionals exposed to formaldehyde, studies in industrial workers, who are thought to have higher exposures, have shown inconsistent associations. We extended follow-up of a cohort of industrial workers to evaluate the association between formaldehyde exposure and lymphohematopoietic cancers. The cohort consisted of 25 619 workers (865 708 person-years) employed before January 1, 1966, at one of 10 U.S. industrial plants and followed through December 31, 1994. We analyzed formaldehyde exposure (peak exposure, average exposure intensity, cumulative exposure, and duration of exposure) and mortality from lymphohematopoietic malignancies using standardized mortality ratios and relative risks and 95% confidence intervals (CIs) based on Poisson regression. Statistical tests were two-sided. Among the cohort, there were 178 deaths from lymphohematopoietic malignancies. Relative risks for leukemia (69 deaths), particularly for myeloid leukemia (30 deaths), increased with formaldehyde exposure. Compared with workers exposed to low peak levels of formaldehyde (0.1-1.9 ppm), relative risks for myeloid leukemia were 2.43 (95% CI = 0.81 to 7.25) and 3.46 (95% CI = 1.27 to 9.43) for workers exposed to peak levels of 2.0-3.9 ppm and > or = 4.0 ppm, respectively (P(trend) =.009). Compared with workers exposed to low levels of average exposure intensity of formaldehyde (0.1-0.4 ppm), workers exposed to 0.5-0.9 ppm and > or = 1.0 ppm average intensity had relative risks of 1.15 (95% CI = 0.41 to 3.23) and 2.49 (95% CI = 1.03 to 6.03), respectively (P(trend) =.088). The relative risk for leukemia was not associated with cumulative exposure but was weakly associated with duration of exposure. Relative risks for Hodgkin's disease also increased with formaldehyde exposure. Exposure to formaldehyde may cause leukemia, particularly myeloid leukemia, in humans. However, results from other investigations are mixed, suggesting caution in drawing definitive conclusions. JF - Journal of the National Cancer Institute AU - Hauptmann, Michael AU - Lubin, Jay H AU - Stewart, Patricia A AU - Hayes, Richard B AU - Blair, Aaron AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. hauptmann@nih.gov Y1 - 2003/11/05/ PY - 2003 DA - 2003 Nov 05 SP - 1615 EP - 1623 VL - 95 IS - 21 KW - Carcinogens KW - 0 KW - Disinfectants KW - Fixatives KW - Formaldehyde KW - 1HG84L3525 KW - Index Medicus KW - Odds Ratio KW - Disinfectants -- adverse effects KW - Humans KW - Cohort Studies KW - Adult KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Fixatives -- adverse effects KW - Male KW - Chemical Industry KW - Lymphoma -- mortality KW - Hematologic Neoplasms -- chemically induced KW - Occupational Exposure -- adverse effects KW - Lymphoma -- chemically induced KW - Formaldehyde -- adverse effects KW - Occupational Diseases -- chemically induced KW - Occupational Diseases -- mortality KW - Hematologic Neoplasms -- mortality KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71346246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mortality+from+lymphohematopoietic+malignancies+among+workers+in+formaldehyde+industries.&rft.au=Hauptmann%2C+Michael%3BLubin%2C+Jay+H%3BStewart%2C+Patricia+A%3BHayes%2C+Richard+B%3BBlair%2C+Aaron&rft.aulast=Hauptmann&rft.aufirst=Michael&rft.date=2003-11-05&rft.volume=95&rft.issue=21&rft.spage=1615&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=1460-2105&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-26 N1 - Date created - 2003-11-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 2004 Jun 16;96(12):966-7; author reply 967-8 [15199116] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of ethanol on the central oscillator in essential tremor. AN - 85376682; pmid-14639668 AB - We investigated the effects of ethanol and diazepam on the central, mechanical, and mechanical reflex components of tremor in patients with essential tremor (ET). A double-blind crossover study (ethanol or diazepam) was conducted on 2 separate days. Dose of ethanol or diazepam was calculated in each individual according to height, weight, and age in 10 patients with ET. The postural tremor amplitude at the wrist was recorded using a three-dimensional accelerometer placed on the dorsum of the hand. Electromyogram (EMG) was recorded with surface electrodes placed on the forearm extensors and flexors. To separate central and mechanical (reflex) components, a 500-g weight was placed on the dorsum of the hand during a second tremor measurement. Tremor recordings were done at baseline and 30, 60, 90, and 120 minutes after drug ingestion. Ethanol and diazepam blood levels were measured at baseline and after 20, 40, 80, and 120 minutes. Blood ethanol and diazepam levels were highest after 40 and 80 minutes. The amplitude of the central component 60 minutes after ingestion of ethanol was decreased significantly (P = 0.029) compared with diazepam. Our findings suggest that the improvement in tremor after ethanol ingestion was due, at least in part, to an effect on a central oscillator. JF - Movement disorders : official journal of the Movement Disorder Society AU - Zeuner, Kirsten E AU - Molloy, Fiona M AU - Shoge, Richard O AU - Goldstein, Susanne R AU - Wesley, Robert AU - Hallett, Mark AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1428, USA. Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 1280 EP - 1285 VL - 18 IS - 11 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - *Biological Clocks: drug effects KW - *Central Nervous System Stimulants: therapeutic use KW - Cross-Over Studies KW - Double-Blind Method KW - Electromyography KW - Essential Tremor: diagnosis KW - *Essential Tremor: drug therapy KW - Essential Tremor: epidemiology KW - *Ethanol: therapeutic use KW - Female KW - Humans KW - Male KW - Middle Aged KW - Parkinson Disease: diagnosis KW - Parkinson Disease: drug therapy KW - Parkinson Disease: epidemiology KW - Questionnaires UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85376682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Effect+of+ethanol+on+the+central+oscillator+in+essential+tremor.&rft.au=Zeuner%2C+Kirsten+E%3BMolloy%2C+Fiona+M%3BShoge%2C+Richard+O%3BGoldstein%2C+Susanne+R%3BWesley%2C+Robert%3BHallett%2C+Mark&rft.aulast=Zeuner&rft.aufirst=Kirsten&rft.date=2003-11-01&rft.volume=98&rft.issue=3&rft.spage=584&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - The von Hippel-Lindau gene and protein in tumorigenesis and angiogenesis: a potential target for therapeutic designs. AN - 75754420; 14529485 AB - The von Hippel-Lindau (VHL) protein is able to suppress tumor growth and to down-regulate many angiogenic factors, and is ubiquitously detected in adult and fetal tissues. This makes VHL an excellent target for therapeutic intervention. Observation of VHL alterations in sporadic tumors has been increasing as a result of examination of abnormalities other than intragenic mutations. These abnormalities include loss of chromosome 3p25, changes in the promoter, down-regulation of transcript, and changes in protein level. This article also presents the finding of differential expression of two common VHL proteins among rat tissues, suggesting tissue- and development-dependent functional difference between these two isoforms. Molecular pathways linking VHL to angiogenesis have been extensively characterized and mechanisms have been proposed to explain how altered VHL leads to tumorigenesis. VHL functions in the presence of oxygen and/or oxygen species. Two strategies are proposed here for anti-tumor and anti-angiogenic treatments of VHL-deficient tumors and those without detectable VHL intragenic mutations. One is to restore wild-type VHL function in VHL-deficient tumors and the other is to enhance wild-type VHL expression and activity in tumors under hypoxic conditions. JF - Current medicinal chemistry AU - Shiao, Yih-Horng AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA. shiao@mail.ncifcrf.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 2461 EP - 2470 VL - 10 IS - 22 SN - 0929-8673, 0929-8673 KW - Tumor Suppressor Proteins KW - 0 KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - VHL protein, human KW - EC 6.3.2.- KW - Index Medicus KW - Animals KW - Humans KW - Mutation KW - Genes, Tumor Suppressor KW - Ubiquitin-Protein Ligases -- genetics KW - Tumor Suppressor Proteins -- metabolism KW - Neovascularization, Pathologic -- genetics KW - von Hippel-Lindau Disease -- genetics KW - Tumor Suppressor Proteins -- genetics KW - Ubiquitin-Protein Ligases -- metabolism KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75754420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+medicinal+chemistry&rft.atitle=The+von+Hippel-Lindau+gene+and+protein+in+tumorigenesis+and+angiogenesis%3A+a+potential+target+for+therapeutic+designs.&rft.au=Shiao%2C+Yih-Horng&rft.aulast=Shiao&rft.aufirst=Yih-Horng&rft.date=2003-11-01&rft.volume=10&rft.issue=22&rft.spage=2461&rft.isbn=&rft.btitle=&rft.title=Current+medicinal+chemistry&rft.issn=09298673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-15 N1 - Date created - 2003-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - VHL down-regulation and differential localization as mechanisms in tumorigenesis. AN - 75753164; 14531799 AB - The von Hippel-Lindau (VHL) gene has been widely analyzed in many tumors. Early studies in animal tumors suggest that changes in VHL protein level and localization may be also important in tumorigenesis. In this study, we determined the role of VHL protein in human renal cell carcinomas. Seventy-five human renal cell carcinomas, predominantly of clear cell type (60 of 75), were examined for VHL protein by immunohistochemistry. The level and pattern of protein expression were then compared to VHL mutations and tumor characteristics. An apparent decline of VHL level (positive in <50% of tumor cells) was observed in 49 (65%) tumors, a change more frequent than VHL mutations (28 of 75) (37%). In tumors, VHL was localized to the cytoplasm and/or the cell membrane. The occurrence of a predominantly membranous signal was significantly associated with missense mutations (9 of 14 tumors with missense mutations versus 14 of 61 tumors with no or nonmissense mutations, P = 0.0025) and tumor stage (23 of 60 tumors with stage TI versus 0 of 15 tumors with TII and TIII, P = 0.0034). This study provides the first evidence of the role of VHL protein level and intracellular localization in tumorigenesis in humans. JF - Kidney international AU - Shiao, Yih-Horng AU - Forsti, Asta AU - Egevad, Lars AU - Anderson, Lucy M AU - Lindblad, Per AU - Hemminki, Kari AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA. shiao@mail.ncifcrf.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 1671 EP - 1674 VL - 64 IS - 5 SN - 0085-2538, 0085-2538 KW - Antibodies KW - 0 KW - Tumor Suppressor Proteins KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - VHL protein, human KW - EC 6.3.2.- KW - Index Medicus KW - Phenotype KW - Genotype KW - Neoplasm Staging KW - Down-Regulation KW - Humans KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- pathology KW - Tumor Suppressor Proteins -- immunology KW - Carcinoma, Renal Cell -- metabolism KW - Ubiquitin-Protein Ligases -- immunology KW - Ubiquitin-Protein Ligases -- genetics KW - Tumor Suppressor Proteins -- metabolism KW - Kidney Neoplasms -- metabolism KW - Tumor Suppressor Proteins -- genetics KW - Ubiquitin-Protein Ligases -- metabolism KW - Mutation, Missense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75753164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=VHL+down-regulation+and+differential+localization+as+mechanisms+in+tumorigenesis.&rft.au=Shiao%2C+Yih-Horng%3BForsti%2C+Asta%3BEgevad%2C+Lars%3BAnderson%2C+Lucy+M%3BLindblad%2C+Per%3BHemminki%2C+Kari&rft.aulast=Shiao&rft.aufirst=Yih-Horng&rft.date=2003-11-01&rft.volume=64&rft.issue=5&rft.spage=1671&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 - 2004-06-24 N1 - Date created - 2003-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of [18F]FP-TZTP binding by loading doses of muscarinic agonists P-TZTP or FP-TZTP in vivo is not due to agonist-induced reduction in cerebral blood flow. AN - 73581926; 12923818 AB - [(18)F][3-(3-(3-Fluoropropyl)thio)-1,2,5-thiadiazol-4-yl]-1,2,5,6-tetrahydro-1-methylpyridine ([(18)F]FP-TZTP) is an M2 selective muscarinic agonist that may allow noninvasive studies of Alzheimer's disease with PET. 3-(3-(Propylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine (P-TZTP), a nonfluorinated analog of FP-TZTP, and unlabeled FP-TZTP inhibited [(18)F]FP-TZTP binding in vivo. Because muscarinic action of the loading dose of P-TZTP administered might have had pharmacological effects, the apparent inhibition might have resulted from reduced delivery rather than competition with receptor-binding. Therefore, we examined the effects of P-TZTP or FP-TZTP administration on cerebral blood flow (CBF) measured by the [(14)C]iodoantipyrine method and laser-Doppler flowmetry in rats. Statistically significant synchronous decreases in both CBF and mean arterial blood pressure (MABP) were observed within the first minute following administration. The decreases in both CBF and MABP were prevented by pretreatment with atropine methyl bromide (M-At), a peripheral muscarinic antagonist, and coadministration of M-At with either FP-TZTP or P-TZTP resulted in the same degree of inhibition of cerebral [(18)F]FP-TZTP-uptake 30 min after administration as observed without M-At. Also, with programmed infusions designed to produce constant arterial concentrations of [(18)F]FP-TZTP and FP-TZTP, which avoid changes in CBF, significant inhibition of [(18)F]FP-TZTP-binding by FP-TZTP was observed. These results indicate that inhibition of [(18)F]FP-TZTP-binding in the brain by P-TZTP or FP-TZTP in vivo occurs independently of their effects on CBF. The methods employed here may also be of interest to evaluate physiological effects of blocking agents utilized to validate other radiopharmaceuticals. Published 2003 Wiley-Liss, Inc. JF - Synapse (New York, N.Y.) AU - Shimoji, Kazuaki AU - Esaki, Takanori AU - Itoh, Yoshiaki AU - Ravasi, Laura AU - Cook, Michelle AU - Jehle, Jane AU - Jagoda, Elaine M AU - Kiesewetter, Dale O AU - Schmidt, Kathleen AU - Sokoloff, Louis AU - Eckelman, William C AD - Positron Emission Tomography Department, Clinical Center, NIMH, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 151 EP - 163 VL - 50 IS - 2 SN - 0887-4476, 0887-4476 KW - 3-(3-(propylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine KW - 0 KW - Atropine Derivatives KW - Carbon Radioisotopes KW - FP-TZTP KW - Fluorine Radioisotopes KW - Muscarinic Agonists KW - Pyridines KW - Receptor, Muscarinic M2 KW - Thiadiazoles KW - Thiazoles KW - methylatropine KW - 80719I460H KW - Antipyrine KW - T3CHA1B51H KW - iodoantipyrine KW - V30V6H1QX4 KW - Index Medicus KW - Animals KW - Blood Pressure -- physiology KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Binding, Competitive -- physiology KW - Binding, Competitive -- drug effects KW - Fluorine Radioisotopes -- metabolism KW - Laser-Doppler Flowmetry KW - Drug Administration Routes KW - Drug Interactions -- physiology KW - Radionuclide Imaging KW - Muscarinic Agonists -- pharmacokinetics KW - Rats KW - Rats, Sprague-Dawley KW - Atropine Derivatives -- pharmacology KW - Blood Pressure -- drug effects KW - Muscarinic Agonists -- metabolism KW - Male KW - Antipyrine -- analogs & derivatives KW - Cerebrovascular Circulation -- drug effects KW - Cerebrovascular Circulation -- physiology KW - Pyridines -- pharmacokinetics KW - Receptor, Muscarinic M2 -- drug effects KW - Brain -- metabolism KW - Brain -- diagnostic imaging KW - Thiazoles -- pharmacology KW - Thiazoles -- pharmacokinetics KW - Brain -- physiopathology KW - Receptor, Muscarinic M2 -- deficiency KW - Thiazoles -- metabolism KW - Pyridines -- metabolism KW - Pyridines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73581926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+%5B18F%5DFP-TZTP+binding+by+loading+doses+of+muscarinic+agonists+P-TZTP+or+FP-TZTP+in+vivo+is+not+due+to+agonist-induced+reduction+in+cerebral+blood+flow.&rft.au=Shimoji%2C+Kazuaki%3BEsaki%2C+Takanori%3BItoh%2C+Yoshiaki%3BRavasi%2C+Laura%3BCook%2C+Michelle%3BJehle%2C+Jane%3BJagoda%2C+Elaine+M%3BKiesewetter%2C+Dale+O%3BSchmidt%2C+Kathleen%3BSokoloff%2C+Louis%3BEckelman%2C+William+C&rft.aulast=Shimoji&rft.aufirst=Kazuaki&rft.date=2003-11-01&rft.volume=50&rft.issue=2&rft.spage=151&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 - 2004-02-24 N1 - Date created - 2003-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement of metastatic potential of mouse B16-melanoma cells to lung after treatment with gangliosides of B-16-melanoma cells of higher metastatic potential to lung. AN - 71586969; 15332492 AB - Mouse B16LuF1 melanoma cells of lower metastatic potential to lung were treated in vitro with same concentration (50 microM) of gangliosides isolated from B16LuF5, B16LuF9 or B16LuF10 cells with higher metastatic potential to lung (LuF1< LuF5< LuF9< LuF10) and injected to groups of normal mice through tail vein. The number of metastatic tumor nodules formed in lung increased in mice receiving B16LuF5, B16LuF9 and B16LuF10-ganglioside-treated B16LuF1 cells compared to mice receiving B16LuF1 cells without any ganglioside treatment. Metastatic potential of B16LuF1 cells gradually increased after treatment with gangliosides of B 16-melanoma cells of increasing metastatic potential to lung. The six major gangliosides isolated from B16LuF10 cells corresponded with standard gangliosides GT1b, GD1b, GD1a, GM1, GM2 and GM3 respectively on TLC-analysis. When B16LuF1 cells were treated in vitro with each of these six individual gangliosides and injected to groups of normal mice through tail vein the number of tumor nodules formed in lung varied. The four groups of mice receiving B16LuF1 cells treated with each of four gangliosides corresponding to GT1b, GD1b, GD1a or GM1 produced lung metastasis comparable to that of untreated control group. Only remaining two gangliosides which corresponded with standard gangliosides GM2 and GM3 increased metastatic potential of B16LuF1 cells. Thus, these results indicated that gangliosides GM2 and GM3 of B16-melanoma cells are definitely associated with metastatic potential of these tumor cells. JF - Indian journal of experimental biology AU - Saha, S AU - Mohanty, K C AD - Department of Metabolic Regulation, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700 026, India. cncinst@giascl01.vsnl.net.in Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 1253 EP - 1258 VL - 41 IS - 11 SN - 0019-5189, 0019-5189 KW - Antigens, Tumor-Associated, Carbohydrate KW - 0 KW - Gangliosides KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Mice, Inbred C57BL KW - Lung -- drug effects KW - Mice KW - Gangliosides -- isolation & purification KW - Antigens, Tumor-Associated, Carbohydrate -- toxicity KW - Melanoma, Experimental -- secondary KW - Lung Neoplasms -- chemistry KW - Lung Neoplasms -- secondary KW - Antigens, Tumor-Associated, Carbohydrate -- isolation & purification KW - Neoplasm Metastasis -- pathology KW - Melanoma, Experimental -- chemistry KW - Gangliosides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71586969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Indian+journal+of+experimental+biology&rft.atitle=Enhancement+of+metastatic+potential+of+mouse+B16-melanoma+cells+to+lung+after+treatment+with+gangliosides+of+B-16-melanoma+cells+of+higher+metastatic+potential+to+lung.&rft.au=Saha%2C+S%3BMohanty%2C+K+C&rft.aulast=Saha&rft.aufirst=S&rft.date=2003-11-01&rft.volume=36&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Journal+of+Microbiology%2C+Immunology+and+Infection&rft.issn=16841182&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-16 N1 - Date created - 2004-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroimaging and mechanisms of drug abuse: interface of molecular imaging and molecular genetics. AN - 71568622; 15024965 AB - Whereas ligand studies can inform the end-products of dysregulation of genetic expression, reporter gene imaging can provide the means to understand the genetic origin of these end-products. As with radioligand studies, in vivo direct measurement of gene expression will allow genetic processes to be monitored over time in the same subject, use of a subject as his/her own control in intervention studies (i.e., measurement before and after an intervention), and monitoring the spatial distribution of molecular events in the whole brain. Furthermore, reporter gene imaging, by advancing knowledge of the biologic mechanisms of disease states, has important clinical implications, particularly in the development and monitoring of treatments. We expect PET to play a prominent role in the elucidation of substance abuse mechanisms and contribute significantly to the development of innovative treatment strategies. JF - Neuroimaging clinics of North America AU - Ernst, Monique AU - Kimes, Alane S AU - Jazbec, Sandra AD - Mood and Anxiety Disorders Program, Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, 15K North Drive, Room 118, MSC 2670, Bethesda, MD 20892-2670, USA. ernstm@intra.nimh.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 833 EP - 849 VL - 13 IS - 4 SN - 1052-5149, 1052-5149 KW - Radiopharmaceuticals KW - 0 KW - Index Medicus KW - Humans KW - Genes, Reporter KW - Predictive Value of Tests KW - Gene Expression Regulation -- drug effects KW - Tomography, Emission-Computed, Single-Photon KW - Tomography, Emission-Computed KW - Brain -- metabolism KW - Substance-Related Disorders -- metabolism KW - Substance-Related Disorders -- diagnostic imaging KW - Brain -- diagnostic imaging KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71568622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroimaging+clinics+of+North+America&rft.atitle=Neuroimaging+and+mechanisms+of+drug+abuse%3A+interface+of+molecular+imaging+and+molecular+genetics.&rft.au=Ernst%2C+Monique%3BKimes%2C+Alane+S%3BJazbec%2C+Sandra&rft.aulast=Ernst&rft.aufirst=Monique&rft.date=2003-11-01&rft.volume=13&rft.issue=4&rft.spage=833&rft.isbn=&rft.btitle=&rft.title=Neuroimaging+clinics+of+North+America&rft.issn=10525149&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-07 N1 - Date created - 2004-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomics and variation of ionotropic glutamate receptors. AN - 71509276; 14684433 AB - Sequencing of the human, mouse, and rat genomes has enabled a comprehensive informatics approach to gene families. This approach is informative for identification of new members of gene families, for cross-species sequence conservation related to functional conservation, for within-species diversity related to functional variation, and for historical effects of selection. This genome informatics approach also focuses our attention on genes whose genomic locations coincide with linkages to phenotypes. We are identifying ionotropic glutamate receptor (IGR) sequence variation by resequencing technologies, including denaturing high-performance liquid chromoatography (dHPLC), for screening and direct sequencing, and by information mining of public (e.g., dbSNP and ENSEMBL) and private (i.e., Celera Discovery System) sequence databases. Each of the 16 known IGRs is represented in these databases, their positions on a canonical physical map (for example, the Celera map) are established, and comparison to mouse and rat sequences has been performed, revealing substantial conservation of these genes, which are located on different chromosomes but found within syntenic groups of genes. A collection of 38 missense variants were identified by the informatics and resequencing approaches in several of these receptor genes, including GRIN2B, GRIN3B, GRIA2, GRIA3, and GRIK1. This represents only a fraction of the sequence variation across these genes, but, in fact, these may constitute a large fraction of the common polymorphisms at these genes, and these polymorphisms are a starting point for understanding the role of these receptors in neurogenetic variation. Genetically influenced human neurobehavioral phenotypes that are likely to be linked to IGR genetic variants include addictions, anxiety/dysphoria disorders, post-brain injury behavioral disorders, schizophrenia, epilepsy, pain perception, learning, and cognition. Thus, the effects of glutamate receptor variation may be protean, and the task of relating variation to behavior difficult. However, functional variants of (1) catechol-O-methyltransferase, (2) serotonin transporter, and (3) brain-derived neurotrophic factor have recently been linked both to behavioral differences and to intermediate phenotypes, suggesting a pathway by which functional variation at IGRs can be tied to an etiologically complex phenotype. JF - Annals of the New York Academy of Sciences AU - Lipsky, Robert H AU - Goldman, David AD - Laboratory of Neurogenetics, National Institute on Alcoholism and Alcohol Abuse, National Institutes of Health, Rockville, Maryland 20852, USA. rlipsky@mail.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 22 EP - 35 VL - 1003 SN - 0077-8923, 0077-8923 KW - Receptors, Glutamate KW - 0 KW - Index Medicus KW - Substance-Related Disorders -- physiopathology KW - Phylogeny KW - Animals KW - Pain -- physiopathology KW - Polymorphism, Genetic -- genetics KW - Humans KW - Pain -- genetics KW - Schizophrenia -- genetics KW - Schizophrenia -- physiopathology KW - Chromosomes -- genetics KW - Substance-Related Disorders -- genetics KW - Receptors, Glutamate -- genetics KW - Receptors, Glutamate -- drug effects KW - Receptors, Glutamate -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71509276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genomics+and+variation+of+ionotropic+glutamate+receptors.&rft.au=Lipsky%2C+Robert+H%3BGoldman%2C+David&rft.aulast=Lipsky&rft.aufirst=Robert&rft.date=2003-11-01&rft.volume=1003&rft.issue=&rft.spage=22&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 - 2004-02-13 N1 - Date created - 2003-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Overview of recent experimental studies on liver stem cells. AN - 71508887; 14722808 AB - Since our review of the experimental evidence for liver epithelial stem cells in 1997, a large body of new data has been added. The new studies have focused on the analysis of differentiation of candidate liver stem cells when they are transplanted into the liver in vivo and when cultured in vitro under defined conditions. The new studies that we review substantiate the existence of stem cells that can generate new lineages of hepatocytes and cholangiocytes, especially in severely damaged livers. However, the recent studies have introduced new areas of controversy about the essential nature of liver stem cells and about appropriate methods to analyze their properties and functions. Whether the major stem cell for hepatocytes and cholangiocytes is an endodermal epithelial cell that resides in the liver or a mesodermal cell from bone marrow is a current area of controversy. Another controversial topic concerns the appropriateness of cell culture to analyze liver epithelial cells. Both of these situations are addressed, if not yet conclusively solved, by the new data. From our review of recent data, we conclude that the major liver stem cell is an epithelial cell that is a liver resident, and that cell culture is a valuable, even necessary, adjunct for analyzing the properties of liver stem cells and for eventually identifying the molecular mechanisms that regulate their activation, proliferation, and differentiation. JF - Seminars in liver disease AU - Thorgeirsson, Snorri S AU - Grisham, Joe W AD - Laboratory of Experimental Carcinogenesis National Cancer Institute, National Institutes of Health Bethesda, Maryland 20892, USA. snorri_thorgeirsson@nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 303 EP - 312 VL - 23 IS - 4 SN - 0272-8087, 0272-8087 KW - Index Medicus KW - Animals KW - Pancreas -- cytology KW - Cell Differentiation -- physiology KW - Humans KW - Embryo, Mammalian -- cytology KW - Hepatocytes -- transplantation KW - Hematopoietic Stem Cell Transplantation KW - Fetus -- cytology KW - Bone Marrow Cells -- cytology KW - Liver -- cytology KW - Stem Cells -- cytology KW - Stem Cells -- physiology KW - Liver -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71508887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+liver+disease&rft.atitle=Overview+of+recent+experimental+studies+on+liver+stem+cells.&rft.au=Thorgeirsson%2C+Snorri+S%3BGrisham%2C+Joe+W&rft.aulast=Thorgeirsson&rft.aufirst=Snorri&rft.date=2003-11-01&rft.volume=23&rft.issue=4&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Seminars+in+liver+disease&rft.issn=02728087&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-25 N1 - Date created - 2004-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hereditary kidney cancer. AN - 71505284; 14680318 AB - Significant advances have been made in the understanding of the genetic basis of familial renal neoplasia. Identification of key genes in the pathogenesis of various hereditary renal cancer syndromes has provided opportunities to screen family members at risk and to explore the significance of these genetic abnormalities in the development and genesis of much more common sporadic counterparts. As researchers continue to delineate critical carcinogenic pathways and accumulate expansive knowledge on oncogenic mechanisms driving cancer initiation and progression at the cellular and molecular levels, this information will be integrated and translated into effective diagnostic and therapeutic strategies that will dictate clinical management of all renal cancers. JF - The Urologic clinics of North America AU - Hwang, Jonathan J AU - Uchio, Edward M AU - Linehan, W Marston AU - Walther, McClellan M AD - Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bldg#10, Room 2B47, Bethesda, MD 20892, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 831 EP - 842 VL - 30 IS - 4 SN - 0094-0143, 0094-0143 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - von Hippel-Lindau Disease KW - Tuberous Sclerosis -- genetics KW - Kidney Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71505284?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Urologic+clinics+of+North+America&rft.atitle=Hereditary+kidney+cancer.&rft.au=Hwang%2C+Jonathan+J%3BUchio%2C+Edward+M%3BLinehan%2C+W+Marston%3BWalther%2C+McClellan+M&rft.aulast=Hwang&rft.aufirst=Jonathan&rft.date=2003-11-01&rft.volume=30&rft.issue=4&rft.spage=831&rft.isbn=&rft.btitle=&rft.title=The+Urologic+clinics+of+North+America&rft.issn=00940143&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-08 N1 - Date created - 2003-12-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of gene knockout and transgenic mice in the study of xenobiotic metabolism. AN - 71504516; 14705864 AB - The role of P450s in xenobiotic metabolism, toxicity, and carcinogenicity has been studied for many years by using in vitro approaches and limited in vivo investigations. Genetic analysis to study the effects of xenobiotics in intact animals has only recently been carried out by use of gene knockout mice. Mice lacking expression of these enzymes have no or only modest phenotypes, indicating that their xenobiotic-metabolizing enzymes are not critical for mammalian development or physiological homeostasis. The null mice have been used to study the roll of xenobiotic-metabolizing enzymes in chemical toxicity and carcinogenicity. There are marked species differences in the expression and catalytic activities of P450s that metabolize xenobiotics, and this complicates the extrapolation of data obtained in rodents for use in drug development and human risk assessment. This is especially notable between mice and rats, commonly used experimental models, and humans. To begin to develop more predictive models, P450 humanized mice were produced and characterized by using genomic clones containing the complete coding and regulatory regions of genes, as transgenes. Humanized lines expressing CYP2D6 and CYP3A4 human P450 were characterized and found to accurately express human P450 proteins and catalytic activities at levels comparable to or higher than the corresponding activities found in human tissues. These novel mouse lines offer the opportunity to predict human drug and carcinogen metabolism and disposition and to search for endogenous substrates for human P450s. JF - Drug metabolism reviews AU - Gonzalez, Frank J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20814, USA. fjgonz@helix.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 319 EP - 335 VL - 35 IS - 4 SN - 0360-2532, 0360-2532 KW - Xenobiotics KW - 0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - Mice, Transgenic KW - Mice, Knockout KW - Models, Animal KW - Cytochrome P-450 Enzyme System -- deficiency KW - Cytochrome P-450 Enzyme System -- genetics KW - Xenobiotics -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Xenobiotics -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71504516?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+reviews&rft.atitle=Role+of+gene+knockout+and+transgenic+mice+in+the+study+of+xenobiotic+metabolism.&rft.au=Gonzalez%2C+Frank+J&rft.aulast=Gonzalez&rft.aufirst=Frank&rft.date=2003-11-01&rft.volume=35&rft.issue=4&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+reviews&rft.issn=03602532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-12 N1 - Date created - 2004-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ocular expression of vascular cell adhesion molecule (VCAM-1) in 2-butoxyethanol-induced hemolysis and thrombosis in female rats. AN - 71498331; 14703767 AB - We demonstrated previously that exposure of rats to 2-butoxyethanol (BE) was associated with morphological changes in red blood cells, hemolytic anemia, and disseminated thrombosis and infarction in different organs including the eyes. In order to elucidate the mechanism of thrombosis formation, we examined in this study the histology and immunohistochemical expression of vascular cell adhesion molecule-1 (VCAM-1), endothelial intercellular adhesion molecule-1 (ICAM-1), and P-selectin in the eyes of the female F344 rat exposed to 2, 3, or 4 daily doses of BE/250 mg/kg body weight. In this BE hemolysis and thrombosis model, positive VCAM-1 expression occurred only in eyes of rats exposed to 3 and 4 doses and was localized in the iris (epithelium lining the posterior surface, anterior mesenchymal epithelium), ciliary processes (lining epithelium, stromal cells), and retina (hypertrophic retinal pigment epithelium). Only weak immunolabeling was seen in eyes exposed to 2 doses. The appearance of VCAM-1 immunostaining correlated with the development of thrombosis located in the same structures. No change in ICAM-1 or P-selectin expression was seen. This immunolabeling distribution suggests that VCAM-1 functions in the pathogenesis of BE-related thrombosis by promoting adhesion of erythrocytes to the endothelium. JF - Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie AU - Nyska, Abraham AU - Moomaw, Cindy R AU - Ezov, Nathan AU - Shabat, Shay AU - Levin-Harrus, Tal AU - Nyska, Meir AU - Redlich, Meir AU - Mittelman, Moshe AU - Yedgar, Saul AU - Foley, Julie F AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-9998, USA. nyska@niehs.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 231 EP - 236 VL - 55 IS - 4 SN - 0940-2993, 0940-2993 KW - Ethylene Glycols KW - 0 KW - P-Selectin KW - Solvents KW - Vascular Cell Adhesion Molecule-1 KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - n-butoxyethanol KW - I0P9XEZ9WV KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Retinal Hemorrhage -- pathology KW - Disease Models, Animal KW - P-Selectin -- metabolism KW - Time Factors KW - Retinal Hemorrhage -- chemically induced KW - Immunoenzyme Techniques KW - Female KW - Intercellular Adhesion Molecule-1 -- metabolism KW - Thrombosis -- chemically induced KW - Hemolysis -- drug effects KW - Solvents -- toxicity KW - Eye -- metabolism KW - Thrombosis -- pathology KW - Ethylene Glycols -- toxicity KW - Vascular Cell Adhesion Molecule-1 -- metabolism KW - Eye -- pathology KW - Eye -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71498331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.atitle=Ocular+expression+of+vascular+cell+adhesion+molecule+%28VCAM-1%29+in+2-butoxyethanol-induced+hemolysis+and+thrombosis+in+female+rats.&rft.au=Nyska%2C+Abraham%3BMoomaw%2C+Cindy+R%3BEzov%2C+Nathan%3BShabat%2C+Shay%3BLevin-Harrus%2C+Tal%3BNyska%2C+Meir%3BRedlich%2C+Meir%3BMittelman%2C+Moshe%3BYedgar%2C+Saul%3BFoley%2C+Julie+F&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=2003-11-01&rft.volume=55&rft.issue=4&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Experimental+and+toxicologic+pathology+%3A+official+journal+of+the+Gesellschaft+fur+Toxikologische+Pathologie&rft.issn=09402993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-20 N1 - Date created - 2004-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of cyclooxygenase-2 with NS-398 and the prevention of radiation-induced transformation, micronuclei formation and clonogenic cell death in C3H 10T1/2 cells. AN - 71478479; 14698956 AB - Abnormally high levels of the cyclooxygenase (COX)-2 isozyme as well as the prostaglandin metabolites produced by the COX pathway have been observed in a variety of malignancies, including cancers of the skin, pancreas, colon, breast, cervix, prostate, and head and neck. Furthermore, exogenous genotoxic agents, including ionizing radiation (IR), have been shown to induce cellular transformation and to elevate COX-2 activity, whereas exposure to agents that specifically inhibit COX-2 activity have been shown to inhibit transformation. These data suggest a possible role of COX-2 both in IR-mediated cellular transformation processes and cell death. C3H 10T1/2 and/or HeLa cells were treated with N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) and/or exposed to IR. Following treatment, cells were assayed for neoplastic transformation, clonogenicity, growth rates, cell cycle distribution, micronuclei formation and DNA damage by established methodologies. Statistical tests were performed on data as described. In the present study, experiments in normal murine fibroblast C3H 10T1/2 cells demonstrated that the chemical inhibition of COX-2 activity with moderate doses of NS-398 abrogated IR-induced transformation events by fourfold and protected irradiated C3H 10T1/2 cells from clonogenic cell death. Considering that these doses of NS-398 had no significant effect on cellular proliferation or cell cycle distribution in C3H 10T1/2 cells, the results suggest that inhibition of COX-2 either increases DNA repair or prevents the accumulation of DNA damage. In supplemental experiments, treatment with NS-398 caused a 1.5-fold reduction in IR-induced micronuclei formation and a significant decrease in DNA damage. These results suggest a role for COX-2 inhibitors in the normal tissue response to IR when administered at therapeutically achievable doses and therefore may have clinical implications for radiation oncology patients in the prevention of IR-induced malignancy. JF - International journal of radiation biology AU - Bisht, K S AU - Bradbury, C M AU - Zoberi, I AU - Curry, H A AU - Kaushal, A AU - Roti Roti, J L AU - Gius, D AD - Molecular Radiation Oncology Section, Radiation Oncology Branch, Radiation Oncology Sciences Program, Center for Cancer Research, National Cancer Institute National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 879 EP - 888 VL - 79 IS - 11 SN - 0955-3002, 0955-3002 KW - Cyclooxygenase 2 Inhibitors KW - 0 KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Nitrobenzenes KW - Sulfonamides KW - N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide KW - 123653-11-2 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Space life sciences KW - Animals KW - Neoplasms -- enzymology KW - DNA Repair KW - DNA Damage KW - Dose-Response Relationship, Drug KW - HeLa Cells KW - Humans KW - Mice KW - Cell Separation KW - Dose-Response Relationship, Radiation KW - Micronucleus Tests KW - Mice, Inbred C3H KW - Neoplasms -- prevention & control KW - Flow Cytometry KW - Time Factors KW - Radiation, Ionizing KW - Cell Division KW - Isoenzymes -- antagonists & inhibitors KW - Nitrobenzenes -- pharmacology KW - Sulfonamides -- pharmacology KW - Micronuclei, Chromosome-Defective -- radiation effects KW - Cell Transformation, Neoplastic KW - Cyclooxygenase Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71478479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+radiation+biology&rft.atitle=Inhibition+of+cyclooxygenase-2+with+NS-398+and+the+prevention+of+radiation-induced+transformation%2C+micronuclei+formation+and+clonogenic+cell+death+in+C3H+10T1%2F2+cells.&rft.au=Bisht%2C+K+S%3BBradbury%2C+C+M%3BZoberi%2C+I%3BCurry%2C+H+A%3BKaushal%2C+A%3BRoti+Roti%2C+J+L%3BGius%2C+D&rft.aulast=Bisht&rft.aufirst=K&rft.date=2003-11-01&rft.volume=79&rft.issue=11&rft.spage=879&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+biology&rft.issn=09553002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-11 N1 - Date created - 2003-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Plastic control of striatal glutamatergic transmission by ensemble actions of several neurotransmitters and targets for drugs of abuse. AN - 71475859; 14684449 AB - Long-lasting alterations in the efficacy of glutamatergic synapses, such as long-term potentiation (LTP) and long-term depression (LTD), are prominent models for mechanisms of information storage in the brain. It has been suggested that exposure to drugs of abuse produces synaptic plasticity at glutamatergic synapses that shares many features with LTP and LTD, and that these synaptic changes may play roles in addiction. We have examined the involvement of particular neurotransmitters in synaptic plasticity at glutamatergic synapses within the striatum, a brain region with prominent roles in initiation and sequencing of actions, as well as habit formation. Our studies indicate that multiple neurotransmitters interact to produce striatal synaptic plasticity, and that the relative strength and patterning of the afferent inputs that release the various neurotransmitters determines whether LTP or LTD is activated. Drugs of abuse interact with glutamatergic synaptic plasticity in multiple ways, including alterations in dopamine release and more direct effects on glutamate release and glutamate receptors. We hypothesize that these effects contribute to addiction by facilitating the formation of new, drug-centered habits, and by disruption of more adaptive behaviors. JF - Annals of the New York Academy of Sciences AU - Lovinger, David M AU - Partridge, John G AU - Tang, Ka-Choi AD - Laboratory for Integrative Neuroscience, Division of Intramural Clinical and Basic Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA. lovindav@mail.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 226 EP - 240 VL - 1003 SN - 0077-8923, 0077-8923 KW - Glutamates KW - 0 KW - Neurotransmitter Agents KW - Index Medicus KW - Behavior -- drug effects KW - Animals KW - Humans KW - Behavior -- physiology KW - Substance-Related Disorders -- physiopathology KW - Neurotransmitter Agents -- physiology KW - Neostriatum -- physiology KW - Glutamates -- physiology KW - Synaptic Transmission -- genetics KW - Neostriatum -- drug effects KW - Neuronal Plasticity -- physiology KW - Neostriatum -- cytology KW - Synaptic Transmission -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71475859?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Plastic+control+of+striatal+glutamatergic+transmission+by+ensemble+actions+of+several+neurotransmitters+and+targets+for+drugs+of+abuse.&rft.au=Lovinger%2C+David+M%3BPartridge%2C+John+G%3BTang%2C+Ka-Choi&rft.aulast=Lovinger&rft.aufirst=David&rft.date=2003-11-01&rft.volume=1003&rft.issue=&rft.spage=226&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 - 2004-02-13 N1 - Date created - 2003-12-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell cycle modulators for the treatment of lung malignancies. AN - 71454203; 14667271 AB - It has become clear in the past decade that most human malignancies, including lung neoplasms, have aberrations in cell cycle control. The tumor suppressor gene retinoblastoma is an important player in the G1/S transition and its function is abnormal in most human neoplasms. Retinoblastoma function is lost as a result of phosphorylation by the cyclin-dependent kinases (CDKs). Thus, modulation of CDKs may have an important use for the therapy and prevention of human neoplasms. Direct CDK modulators are small molecules that target specifically the adenosine triphosphate binding site of CDKs. In contrast, indirect CDK modulators affect CDK function by modulation of upstream pathways required for CDK activation. The first example of a direct small-molecule CDK modulator tested in the clinic, flavopiridol, is a pan-CDK inhibitor that not only promotes cell cycle arrest but also halts transcriptional elongation, promotes apoptosis, induces differentiation, and has antiangiogenic properties. The second example of direct small-molecule CDK modulators tested in clinical trials is UCN-01 (7-hydroxystaurosporine). UCN-01 has interesting preclinical features: it inhibits Ca2+-dependent protein kinase C, promotes apoptosis, arrests cell cycle progression at G1/S, and abrogates checkpoints upon DNA damage. In summary, novel small-molecule CDK modulators are being tested in the clinic with interesting results. Although these small molecules are directed toward a very prevalent cause of carcinogenesis, their role in the clinical armamentarium is still uncertain. JF - Clinical lung cancer AU - Senderowicz, Adrian M AD - Molecular Therapeutics Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4330, USA. sendero@helix.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 158 EP - 168 VL - 5 IS - 3 SN - 1525-7304, 1525-7304 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Protein Kinase C KW - EC 2.7.11.13 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Cyclin-Dependent Kinases -- genetics KW - Protein Kinase C -- drug effects KW - Tumor Cells, Cultured -- cytology KW - Enzyme Inhibitors -- therapeutic use KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Genes, Retinoblastoma -- drug effects KW - Protein Kinase C -- genetics KW - Phosphorylation -- drug effects KW - Apoptosis -- genetics KW - Apoptosis -- drug effects KW - Cyclin-Dependent Kinases -- drug effects KW - Antineoplastic Agents -- therapeutic use KW - Genes, Retinoblastoma -- genetics KW - Staurosporine -- therapeutic use KW - Cell Cycle -- physiology KW - Lung Neoplasms -- therapy KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- physiopathology KW - Cell Cycle -- genetics KW - Staurosporine -- analogs & derivatives KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71454203?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lung+cancer&rft.atitle=Cell+cycle+modulators+for+the+treatment+of+lung+malignancies.&rft.au=Senderowicz%2C+Adrian+M&rft.aulast=Senderowicz&rft.aufirst=Adrian&rft.date=2003-11-01&rft.volume=5&rft.issue=3&rft.spage=158&rft.isbn=&rft.btitle=&rft.title=Clinical+lung+cancer&rft.issn=15257304&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-24 N1 - Date created - 2003-12-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crambescidin 826 and dehydrocrambine A: new polycyclic guanidine alkaloids from the marine sponge Monanchora sp. that inhibit HIV-1 fusion. AN - 71432125; 14640525 AB - Two new polycyclic guanidine alkaloids, crambescidin 826 (1) and dehydrocrambine A (2), and the known compounds crambescidin 800 (3) and fromiamycalin (4) were isolated from the marine sponge Monanchora sp. The structures of 1 and 2 were elucidated by 2D NMR and mass spectrometry, and relative stereochemistry was established by analysis of coupling constants and ROESY spectra. The pentacyclic guanidine alkaloids 1, 3, and 4 inhibit HIV-1 envelope-mediated fusion in vitro with IC(50)'s of 1-3 microM, while compound 2, a tricyclic guanidine alkaloid, showed weaker inhibition, with an IC(50) of approximately 35 microM. JF - Journal of natural products AU - Chang, LengChee AU - Whittaker, Noel F AU - Bewley, Carole A AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, Maryland 20892-0820. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 1490 EP - 1494 VL - 66 IS - 11 SN - 0163-3864, 0163-3864 KW - Alkaloids KW - 0 KW - Anti-HIV Agents KW - Guanidines KW - Spiro Compounds KW - crambescidin 826 KW - dehydrocrambine A KW - Index Medicus KW - Molecular Structure KW - Animals KW - Nuclear Magnetic Resonance, Biomolecular KW - Palau KW - Inhibitory Concentration 50 KW - Anti-HIV Agents -- chemistry KW - Spiro Compounds -- pharmacology KW - Alkaloids -- chemistry KW - Spiro Compounds -- chemistry KW - Anti-HIV Agents -- pharmacology KW - Porifera -- chemistry KW - Alkaloids -- pharmacology KW - Alkaloids -- isolation & purification KW - Anti-HIV Agents -- isolation & purification KW - Spiro Compounds -- isolation & purification KW - Guanidines -- isolation & purification KW - Guanidines -- pharmacology KW - Guanidines -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71432125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+natural+products&rft.atitle=Crambescidin+826+and+dehydrocrambine+A%3A+new+polycyclic+guanidine+alkaloids+from+the+marine+sponge+Monanchora+sp.+that+inhibit+HIV-1+fusion.&rft.au=Chang%2C+LengChee%3BWhittaker%2C+Noel+F%3BBewley%2C+Carole+A&rft.aulast=Chang&rft.aufirst=LengChee&rft.date=2003-11-01&rft.volume=66&rft.issue=11&rft.spage=1490&rft.isbn=&rft.btitle=&rft.title=Journal+of+natural+products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-11 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Urinary mutagenicity and colorectal adenoma risk. AN - 71421962; 14652290 AB - We investigated urinary mutagenicity and colorectal adenoma risk in a clinic-based, case-control study of currently nonsmoking cases (n = 143) and controls (n = 156). Urinary organics were extracted by C18/methanol from 12-h overnight urine samples, and mutagenicity was determined in Salmonella YG1024 +S9 (Ames test). Adenoma risk was 2.4-fold higher in subjects in the highest versus the lowest quintile of urinary mutagenicity (95% confidence interval = 1.1-5.1). Combining urinary mutagenicity with intake of meat-derived mutagenicity (from our earlier analysis) resulted in a 5.6-fold increase in adenoma risk (95% confidence interval = 2.2-13.9, comparing the highest with the lowest quintile). In our study population, diet may have contributed to mutagenic exposure, which was positively associated with colorectal adenoma risk. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Peters, Ulrike AU - DeMarini, David M AU - Sinha, Rashmi AU - Brooks, Lance R AU - Warren, Sarah H AU - Chatterjee, Nilanjan AU - Rothman, Nathaniel AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland 20892-7273, USA. petersu@mail.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 1253 EP - 1256 VL - 12 IS - 11 Pt 1 SN - 1055-9965, 1055-9965 KW - Mutagens KW - 0 KW - Index Medicus KW - Salmonella -- genetics KW - Mutagenicity Tests KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Diet KW - Urinalysis KW - Adolescent KW - Male KW - Female KW - Mutagens -- analysis KW - Colorectal Neoplasms -- etiology KW - Adenoma -- etiology KW - Colorectal Neoplasms -- genetics KW - Adenoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71421962?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Urinary+mutagenicity+and+colorectal+adenoma+risk.&rft.au=Peters%2C+Ulrike%3BDeMarini%2C+David+M%3BSinha%2C+Rashmi%3BBrooks%2C+Lance+R%3BWarren%2C+Sarah+H%3BChatterjee%2C+Nilanjan%3BRothman%2C+Nathaniel&rft.aulast=Peters&rft.aufirst=Ulrike&rft.date=2003-11-01&rft.volume=12&rft.issue=11+Pt+1&rft.spage=1253&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 - 2004-03-16 N1 - Date created - 2003-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson's disease. AN - 71409667; 14637099 AB - Adenosine A(2A) receptors, abundantly expressed on striatal medium spiny neurons, appear to activate signaling cascades implicated in the regulation of coexpressed ionotropic glutamatergic receptors. To evaluate the contribution of adenosinergic mechanisms to the pathogenesis of the response alterations induced by dopaminergic treatment, we studied the ability of the selective adenosine A(2A) receptor antagonist KW-6002 to prevent as well as palliate these syndromes in rodent and primate models of Parkinson's disease. In rats, KW-6002 reversed the shortened motor response produced by chronic levodopa treatment while reducing levodopa-induced hyperphosphorylation at S845 residues on AMPA receptor GluR1 subunits. In primates, KW-6002 evidenced modest antiparkinsonian activity when given alone. Once-daily coadministration of KW-6002 with apomorphine prevented the development of dyskinesias, which appeared in control animals 7-10 days after initiating apomorphine treatment. Animals initially given apomorphine plus KW-6002 for 3 weeks did not begin to manifest apomorphine-induced dyskinesias until 10-12 days after discontinuing the A(2A) antagonist. These results suggest that KW-6002 can attenuate the induction as well as the expression of motor response alterations to chronic dopaminergic stimulation in parkinsonian animals, possibly by blocking A(2A) receptor-stimulated signaling pathways. Our findings strengthen the rationale for developing A(2A) antagonists as an early treatment strategy for Parkinson's disease. JF - Experimental neurology AU - Bibbiani, F AU - Oh, J D AU - Petzer, J P AU - Castagnoli, N AU - Chen, J-F AU - Schwarzschild, M A AU - Chase, T N AD - ETB, NINDS, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 285 EP - 294 VL - 184 IS - 1 SN - 0014-4886, 0014-4886 KW - Adenosine A2 Receptor Antagonists KW - 0 KW - Antiparkinson Agents KW - Dopamine Agonists KW - Purines KW - Receptors, AMPA KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - Sympatholytics KW - glutamate receptor ionotropic, AMPA 1 KW - istradefylline KW - 2GZ0LIK7T4 KW - Levodopa KW - 46627O600J KW - Oxidopamine KW - 8HW4YBZ748 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Animals KW - Dyskinesia, Drug-Induced -- pathology KW - Macaca fascicularis KW - Antiparkinson Agents -- therapeutic use KW - Receptors, AMPA -- metabolism KW - Apomorphine -- toxicity KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- antagonists & inhibitors KW - Denervation KW - Neurons -- pathology KW - Sympatholytics -- toxicity KW - Rats KW - Rats, Sprague-Dawley KW - Sympatholytics -- antagonists & inhibitors KW - Receptors, Dopamine D1 -- agonists KW - Phosphorylation KW - Oxidopamine -- toxicity KW - Oxidopamine -- antagonists & inhibitors KW - Receptors, Dopamine D2 -- agonists KW - Dyskinesia, Drug-Induced -- prevention & control KW - Purines -- pharmacology KW - Levodopa -- therapeutic use KW - Male KW - Parkinson Disease, Secondary -- physiopathology KW - Parkinson Disease, Secondary -- chemically induced KW - Parkinson Disease, Secondary -- pathology KW - Dopamine Agonists -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71409667?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=A2A+antagonist+prevents+dopamine+agonist-induced+motor+complications+in+animal+models+of+Parkinson%27s+disease.&rft.au=Bibbiani%2C+F%3BOh%2C+J+D%3BPetzer%2C+J+P%3BCastagnoli%2C+N%3BChen%2C+J-F%3BSchwarzschild%2C+M+A%3BChase%2C+T+N&rft.aulast=Bibbiani&rft.aufirst=F&rft.date=2003-11-01&rft.volume=184&rft.issue=1&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-05 N1 - Date created - 2003-11-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Exp Neurol. 2003 Nov;184(1):20-3 [14637073] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prostate cancer in Klinefelter syndrome during hormonal replacement therapy. AN - 71388246; 14624928 AB - Prostate cancer detection is a rare occurrence in patients with Klinefelter syndrome, in whom chronically low circulating androgen levels are common findings. Administration of exogenous testosterone has increasingly been used to treat young adolescents diagnosed with Klinefelter syndrome and documented androgen deficiency. Although testosterone replacement in adult patients has been associated with prostatic enlargement, it remains unknown whether chronic supplementation of exogenous testosterone to pubescent males with hypogonadism results in early prostate carcinogenesis. We report a first case of prostate cancer in a patient with Klinefelter syndrome who had undergone long-term testosterone replacement therapy since childhood for chronically depressed levels of testosterone. JF - Urology AU - Hwang, Jonathan J AU - Dharmawardana, Pathirage G AU - Uchio, Edward M AU - Wynberg, Jason AU - Phillips, John L AD - Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1501, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 941 VL - 62 IS - 5 KW - Testosterone KW - 3XMK78S47O KW - Index Medicus KW - Hyperplasia KW - Humans KW - Prostate -- pathology KW - Middle Aged KW - Male KW - Prostatic Intraepithelial Neoplasia -- chemically induced KW - Testosterone -- deficiency KW - Hormone Replacement Therapy -- adverse effects KW - Adenocarcinoma -- chemically induced KW - Testosterone -- adverse effects KW - Prostatic Neoplasms -- chemically induced KW - Klinefelter Syndrome -- complications KW - Neoplasms, Hormone-Dependent -- chemically induced KW - Klinefelter Syndrome -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71388246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Urology&rft.atitle=Prostate+cancer+in+Klinefelter+syndrome+during+hormonal+replacement+therapy.&rft.au=Hwang%2C+Jonathan+J%3BDharmawardana%2C+Pathirage+G%3BUchio%2C+Edward+M%3BWynberg%2C+Jason%3BPhillips%2C+John+L&rft.aulast=Hwang&rft.aufirst=Jonathan&rft.date=2003-11-01&rft.volume=62&rft.issue=5&rft.spage=941&rft.isbn=&rft.btitle=&rft.title=Urology&rft.issn=1527-9995&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-04 N1 - Date created - 2003-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heat shock protein 90. AN - 71384888; 14624223 AB - Heat shock protein 90 (Hsp90) is a molecular chaperone required for the stability and function of a number of conditionally activated and/or expressed signaling proteins, as well as multiple mutated, chimeric, or overexpressed signaling proteins, which promote cancer cell growth or survival or both. Hsp90 inhibitors, by interacting specifically with a single molecular target, cause the inactivation, destabilization, and eventual degradation of Hsp90 client proteins, and they have shown promising antitumor activity in preclinical model systems. One Hsp90 inhibitor, 17-AAG, has completed Phase I clinical trial, and several Phase II trials are in progress. Hsp90 inhibitors are unique in that, although they are directed towards a specific molecular target, they simultaneously inhibit multiple signaling pathways that frequently interact to promote cancer cell survival. Recently identified clients of Hsp90 participate, frequently in overlapping pathways, in mediating cancer cell survival. These include Akt, Her2, and HIF-1 alpha. Thus, by inhibiting multiple survival pathways used by cancer cells, combination of an Hsp90 inhibitor with standard chemotherapeutic agents may dramatically increase the in vivo efficacy of the standard agent. Furthermore, Hsp90 modulates androgen receptor activity and the activity of several mutated kinases characteristic of several leukemias and lymphomas, making Hsp90 inhibition an attractive modality in these cases. Hsp90 inhibitors may circumvent the characteristic genetic plasticity that has allowed cancer cells to eventually evade the toxic effects of most molecularly targeted agents. The mechanism-based use of Hsp90 inhibitors, both alone and in combination with other drugs, should augment the treatment of multiple forms of cancer. JF - Current opinion in oncology AU - Neckers, Len AU - Ivy, S Percy AD - Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850, USA. len@helix.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 419 EP - 424 VL - 15 IS - 6 SN - 1040-8746, 1040-8746 KW - Biomarkers, Tumor KW - 0 KW - HIF1A protein, human KW - HSP90 Heat-Shock Proteins KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Proto-Oncogene Proteins KW - Receptors, Androgen KW - Transcription Factors KW - Vascular Endothelial Growth Factor A KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Index Medicus KW - Neoplasms -- drug therapy KW - Protein-Serine-Threonine Kinases -- metabolism KW - Receptors, Androgen -- drug effects KW - Transcription Factors -- metabolism KW - Humans KW - Protein-Serine-Threonine Kinases -- drug effects KW - Proto-Oncogene Proteins -- metabolism KW - Vascular Endothelial Growth Factor A -- drug effects KW - Genes, erbB-2 -- drug effects KW - Biomarkers, Tumor -- metabolism KW - Transcription Factors -- drug effects KW - Cell Survival -- drug effects KW - Proto-Oncogene Proteins -- drug effects KW - Clinical Trials, Phase I as Topic KW - Receptors, Androgen -- metabolism KW - Vascular Endothelial Growth Factor A -- metabolism KW - Neoplasms -- metabolism KW - HSP90 Heat-Shock Proteins -- therapeutic use KW - HSP90 Heat-Shock Proteins -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71384888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+oncology&rft.atitle=Heat+shock+protein+90.&rft.au=Neckers%2C+Len%3BIvy%2C+S+Percy&rft.aulast=Neckers&rft.aufirst=Len&rft.date=2003-11-01&rft.volume=15&rft.issue=6&rft.spage=419&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+oncology&rft.issn=10408746&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-08 N1 - Date created - 2003-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Co-administration of dextromethorphan with morphine attenuates morphine rewarding effect and related dopamine releases at the nucleus accumbens. AN - 71372791; 14564449 AB - Morphine is one of the most effective analgesics in clinic to treat postoperative pain or cancer pain. A major drawback of its continuous use is the development of tolerance and dependence. In our previous study we found that a widely used antitussive agent in clinics, dextromethorphan [(DM); also known as a non-competitive N-methyl- d-aspartate (NMDA) antagonist], could prevent the development of morphine tolerance. In the present study, we further investigated its effect on morphine addiction. Conditioned place preference (CPP) test and behavioral sensitization of locomotor activity were used to investigate the drug-seeking related behaviors, which were in correlation with psychological dependence. Our results showed that co-administered DM was able to abolish completely the CPP effect induced by morphine, but had no effect on morphine-induced behavioral sensitization. By employing the microdialysis technique in free-moving animals, we also determined the extracellular level of dopamine and serotonin metabolites in the shell region of the nucleus accumbens (NAc) in its response to morphine with/without DM. A significant increase in dopamine metabolites following morphine administration was demonstrated in the NAc. This increase by morphine could be attenuated by co-administered DM, whereas DM itself did not show any effect. Based on our results, it is speculated that DM may effectively attenuate morphine-induced psychological dependence. Neurochemical analysis revealed that the effect of DM could be through its action on the dopaminergic mesolimbic pathway, which could be activated by morphine and attributed to the cause of rewarding. JF - Naunyn-Schmiedeberg's archives of pharmacology AU - Huang, Eagle Y-K AU - Liu, Te-Chen AU - Tao, Pao-Luh AD - Department of Pharmacology, National Defense Medical Center, P.O. Box 90048-504, Nei-Hu, Taipei, Taiwan. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 386 EP - 392 VL - 368 IS - 5 SN - 0028-1298, 0028-1298 KW - Analgesics, Opioid KW - 0 KW - Narcotics KW - Receptors, N-Methyl-D-Aspartate KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - Dextromethorphan KW - 7355X3ROTS KW - Morphine KW - 76I7G6D29C KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Chromatography, High Pressure Liquid KW - Microdialysis KW - Rats KW - Behavior, Animal -- drug effects KW - Rats, Sprague-Dawley KW - 3,4-Dihydroxyphenylacetic Acid -- metabolism KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Conditioning, Operant KW - Dopamine -- biosynthesis KW - Motor Activity -- drug effects KW - Drug Synergism KW - Time Factors KW - Male KW - Reward KW - Nucleus Accumbens -- drug effects KW - Analgesics, Opioid -- pharmacology KW - Dextromethorphan -- pharmacology KW - Nucleus Accumbens -- metabolism KW - Narcotics -- pharmacology KW - Morphine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71372791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Naunyn-Schmiedeberg%27s+archives+of+pharmacology&rft.atitle=Co-administration+of+dextromethorphan+with+morphine+attenuates+morphine+rewarding+effect+and+related+dopamine+releases+at+the+nucleus+accumbens.&rft.au=Huang%2C+Eagle+Y-K%3BLiu%2C+Te-Chen%3BTao%2C+Pao-Luh&rft.aulast=Huang&rft.aufirst=Eagle&rft.date=2003-11-01&rft.volume=368&rft.issue=5&rft.spage=386&rft.isbn=&rft.btitle=&rft.title=Naunyn-Schmiedeberg%27s+archives+of+pharmacology&rft.issn=00281298&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-10 N1 - Date created - 2003-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety and efficacy of convection-enhanced delivery of gemcitabine or carboplatin in a malignant glioma model in rats. AN - 71363705; 14609170 AB - Convection-enhanced delivery (CED) can be used safely to perfuse regions of the central nervous system (CNS) with therapeutic agents in a manner that bypasses the blood-brain barrier (BBB). These features make CED a potentially ideal method for the distribution of potent chemotherapeutic agents with certain pharmacokinetic properties to tumors of the CNS. To determine the safety and efficacy of the CED of two chemotherapeutic agents (with properties ideal for this method of delivery) into the CNS, the authors perfused naive rats and those harboring 9L gliomas with carboplatin or gemcitabine. Dose-escalation toxicity studies were performed by perfusing the striatum (10 microl, 24 rats) and brainstem (10 microl, 16 rats) of naive rats with carboplatin (0.1, 1, and 10 mg/ml) or gemcitabine (0.4, 4, and 40 mg/ml) via CED. Efficacy trials involved the intracranial implantation of 9L tumor cells in 20 Fischer 344 rats. The tumor and surrounding regions were perfused with 40 microl of saline (control group, four rats), 1 mg/ml of carboplatin (four rats), or 4 mg/ml of gemcitabine (four rats) 7 days after implantation. Eight rats harboring the 9L glioma were treated with the systemic administration of 60 mg/kg of carboplatin (four rats) or 150 mg/kg of gemcitabine (four rats) 7 days postimplantation. Clinical, gross, and histological analyses were used to determine toxicity and efficacy. Toxicity occurred in rats that had received only the highest dose of the CED of carboplatin or gemcitabine. Among rats with 9L gliomas, all control and systemically treated animals died within 26 days of tumor implantation. Long-term survival (120 days) and eradication of the tumor occurred in both CED-treated groups (75% of rats in the carboplatin group and 50% of rats in the gemcitabine group). Furthermore, animals harboring the 9L glioma and treated with intratumoral CED of carboplatin or gemcitabine survived significantly longer than controls treated with intratumoral saline (p < 0.01) or systemic chemotherapy (p < 0.01). The perfusion of sensitive regions of the rat brain can be accomplished without toxicity by using therapeutic concentrations of carboplatin or gemcitabine. In addition, CED of carboplatin or gemcitabine to tumors in this glioma model is safe and has potent antitumor effects. These findings indicate that similar treatment paradigms may be useful in the treatment of glial neoplasms in humans. JF - Journal of neurosurgery AU - Degen, Jeffrey W AU - Walbridge, Stuart AU - Vortmeyer, Alexander O AU - Oldfield, Edward H AU - Lonser, Russell R AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 893 EP - 898 VL - 99 IS - 5 SN - 0022-3085, 0022-3085 KW - Antineoplastic Agents KW - 0 KW - Deoxycytidine KW - 0W860991D6 KW - gemcitabine KW - B76N6SBZ8R KW - Carboplatin KW - BG3F62OND5 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Brain Stem -- drug effects KW - Animals KW - Rats, Inbred F344 KW - Brain Stem -- ultrastructure KW - Dose-Response Relationship, Drug KW - Disease Models, Animal KW - Basal Ganglia -- ultrastructure KW - Injections, Intralesional -- methods KW - Basal Ganglia -- drug effects KW - Male KW - Convection KW - Brain Neoplasms -- pathology KW - Glioma -- pathology KW - Deoxycytidine -- toxicity KW - Carboplatin -- toxicity KW - Glioma -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Deoxycytidine -- analogs & derivatives KW - Antineoplastic Agents -- toxicity KW - Deoxycytidine -- administration & dosage KW - Carboplatin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71363705?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurosurgery&rft.atitle=Safety+and+efficacy+of+convection-enhanced+delivery+of+gemcitabine+or+carboplatin+in+a+malignant+glioma+model+in+rats.&rft.au=Degen%2C+Jeffrey+W%3BWalbridge%2C+Stuart%3BVortmeyer%2C+Alexander+O%3BOldfield%2C+Edward+H%3BLonser%2C+Russell+R&rft.aulast=Degen&rft.aufirst=Jeffrey&rft.date=2003-11-01&rft.volume=99&rft.issue=5&rft.spage=893&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-04 N1 - Date created - 2003-11-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incorporating basic nutrition science into health interventions for cancer prevention. AN - 71352355; 14608120 AB - Increasing evidence points to numerous dietary components that modify cancer incidence as well as the biological behavior of tumors. These inhibitory or stimulatory effects depend not only on the dietary component examined, but on a number of factors including the cellular DNA profile (nutrigenetic and nutrigenomic effects), protein formation and regulation (proteomic effect), and the effective delivery of the active intermediate at specific target sites (metabolomic effect). Unfortunately, the diet and cancer research domain is strewn with studies that were inadequately designed to monitor biological endpoints, used invalid biomarkers, or monitored irrelevant intakes or exposures. The scientific frontiers in health risk prediction and disease prevention strategies will greatly expand with the building of reliable nutrition and cancer biomarker databases that use modeling techniques to integrate information about intakes, effect biomarkers, and susceptibility biomarkers. Fundamental to this database will be the elucidation of the specific molecular sites of action (targets) for the specific dietary component. Clustering techniques that build on either genes or ratios of genetic expressions or their products will be needed to assess the merit of a particular dietary intervention. Models are already surfacing about how dietary-induced fluctuations in genes and their expression products can modify pathways associated with carcinogen activation and detoxification, alter rates of cellular proliferation, influence apoptosis, and modify angiogenesis. Embracing new genomic technologies offers exciting opportunities for advancing nutrition, especially those related to cancer prevention. We must effectively communicate, within a responsible bioethical framework, the potential value of knowledge about genes and gene products. JF - The Journal of nutrition AU - Milner, John A AD - Nutritional Science Research Group, Division Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA. milnerj@mail.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 3820S EP - 3826S VL - 133 IS - 11 Suppl 1 SN - 0022-3166, 0022-3166 KW - Proteome KW - 0 KW - Index Medicus KW - Nutritional Requirements KW - DNA Methylation KW - Humans KW - Food KW - Protein Processing, Post-Translational KW - Polymorphism, Single Nucleotide -- genetics KW - Models, Biological KW - Neoplasms -- prevention & control KW - Nutritional Physiological Phenomena KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71352355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=Incorporating+basic+nutrition+science+into+health+interventions+for+cancer+prevention.&rft.au=Milner%2C+John+A&rft.aulast=Milner&rft.aufirst=John&rft.date=2003-11-01&rft.volume=133&rft.issue=11+Suppl+1&rft.spage=3820S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-23 N1 - Date created - 2003-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutations in bladder cancer: evidence for exogenous versus endogenous risk factors. AN - 71350388; 14612556 AB - Bladder cancer is associated with smoking, occupational exposures, and glutathione S-transferase (GST) M1 and N-acetyltransferase (NAT) 2 polymorphisms that may influence carcinogen metabolism, but somatic p53mutations are often CpG dinucleotide G:C-A:T transitions that can occur spontaneously. We conducted a case-control study to determine whether p53mutation characteristics might distinguish cases with environmental versus endogenous causes. p53exons 4-9 were amplified from 146 bladder tumors by PCR, screened by single-strand conformational polymorphism analysis, and sequenced. Thirty-one cases were p53-positive, and 112 were p53-negative (germ line or silent). G:C-A:T transitions were also subclassified as CpG or non-CpG. Cases and 215 clinic controls were interviewed. GSTM1, NAT1, and NAT2 polymorphisms were assayed from peripheral blood. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic and polytomous regression. Case-control ORs for smoking, occupations, and NAT1*10genotype were similar for p53-positive and p53-negative cases. Associations with GSTM1-null and NAT2-slow genotypes were somewhat stronger for p53-positive [OR, 3.3; CI, 1.4-7.8 (GSTM1 null); OR, 1.8; CI, 0.8-4.0 (NAT2 slow)] than p53-negative cases [OR, 1.5; CI:0.9-2.3 (GSTM1 null); OR, 0.9; CI, 0.6-1.4 (NAT2 slow)]. Smoking was strongly associated with CpG G:C-A:T (OR, 15.3; CI:3.6-65) versus other G:C-A:T (OR, 1.8; CI, 0.3-9.8). NAT2 slow genotypes were also associated with CpG G:C-A:T (OR, 6.2; CI:0.7-52), whereas GSTM1 null was associated with non-CpG G:C-A:T (OR, 7.8; CI, 0.9-65). Associations were not substantially different for case subtypes defined by p53mutation status alone. Estimates for p53 subtypes were imprecise but support in vitro evidence that some CpG G:C-A:T transitions may be caused by smoking and other environmental mutagens. JF - Cancer research AU - Schroeder, Jane C AU - Conway, Kathleen AU - Li, Yu AU - Mistry, Kusum AU - Bell, Douglas A AU - Taylor, Jack A AD - Epidemiology Branch, National Institute of Environmental Health Sciences/NIH, 111 Alexander Drive, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/11/01/ PY - 2003 DA - 2003 Nov 01 SP - 7530 EP - 7538 VL - 63 IS - 21 SN - 0008-5472, 0008-5472 KW - Isoenzymes KW - 0 KW - Acetyltransferases KW - EC 2.3.1.- KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - N-acetyltransferase 1 KW - NAT2 protein, human KW - Glutathione Transferase KW - EC 2.5.1.18 KW - glutathione S-transferase M1 KW - Index Medicus KW - Occupational Exposure KW - Sex Factors KW - Polymorphism, Genetic KW - Humans KW - Smoking -- adverse effects KW - Aged KW - Glutathione Transferase -- genetics KW - Risk Factors KW - Case-Control Studies KW - Acetyltransferases -- genetics KW - Middle Aged KW - Genetic Predisposition to Disease KW - Female KW - Male KW - Arylamine N-Acetyltransferase -- genetics KW - Urinary Bladder Neoplasms -- etiology KW - Urinary Bladder Neoplasms -- genetics KW - Genes, p53 -- genetics KW - Urinary Bladder Neoplasms -- enzymology KW - Carcinoma, Transitional Cell -- etiology KW - Mutation KW - Carcinoma, Transitional Cell -- genetics KW - Carcinoma, Transitional Cell -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71350388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+mutations+in+bladder+cancer%3A+evidence+for+exogenous+versus+endogenous+risk+factors.&rft.au=Schroeder%2C+Jane+C%3BConway%2C+Kathleen%3BLi%2C+Yu%3BMistry%2C+Kusum%3BBell%2C+Douglas+A%3BTaylor%2C+Jack+A&rft.aulast=Schroeder&rft.aufirst=Jane&rft.date=2003-11-01&rft.volume=63&rft.issue=21&rft.spage=7530&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 - 2004-01-16 N1 - Date created - 2003-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential induction of topoisomerase I-DNA cleavage complexes by the indenoisoquinoline MJ-III-65 (NSC 706744) and camptothecin: base sequence analysis and activity against camptothecin-resistant topoisomerases I. AN - 71347148; 14612542 AB - Camptothecin (CPT) and its derivatives target mammalian DNA topoisomerase I (top1) and are among the most effective novel anticancer drugs. However, the activity of CPTs is limited by several factors, including drug inactivation by lactone ring opening, tumor drug resistance, and toxicity in patients. Novel top1 inhibitors are being searched to overcome such limitations and expand the anticancer spectrum of camptothecins. MJ-III-65 (NSC 706744) is among the most promising indenoisoquinolines to date. In this study, we show that MJ-III-65 enhances top1 cleavage complexes by both inhibiting their reversal (religation) more efficiently than CPT and by enhancing their formation. The top1 DNA cleavage complexes induced by MJ-III-65 exhibit a different distribution pattern compared with CPT and exhibit different base sequence preferences immediately around the top1 cleavage sites. Although CPTs have a preference for thymine at the (-1) position and guanine at the (+1) position of the top1-mediated DNA cleavage sites, MJ-III-65 can accommodate different base pairs at the (-1), (+1), or (+2) position, with a preference for a cytosine at the (-1) position on the scissile strand. Another difference with CPTs is the activity of MJ-III-65 against CPT-resistant top1 enzymes, implying that the amino acid residue interactions with top1 are different for MJ-III-65 and CPTs. As with CPT, MJ-III-65 is inactive against vaccinia top1. This study shows the specific molecular interactions of MJ-III-65 with top1 and demonstrates that MJ-III-65 is a potentially useful top1 inhibitor that enhances and traps top1 cleavage sites not sensitive to CPTs. JF - Cancer research AU - Antony, Smitha AU - Jayaraman, Muthusamy AU - Laco, Gary AU - Kohlhagen, Glenda AU - Kohn, Kurt W AU - Cushman, Mark AU - Pommier, Yves AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute/NIH, 37 Convent Drive, Bethesda, MD 20892-4255, USA. Y1 - 2003/11/01/ PY - 2003 DA - 2003 Nov 01 SP - 7428 EP - 7435 VL - 63 IS - 21 SN - 0008-5472, 0008-5472 KW - 6-(3-(2-hydroxyethyl)amino-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno(1,2-)isoquinoline KW - 0 KW - Enzyme Inhibitors KW - Indenes KW - Isoquinolines KW - Oligonucleotides KW - Topoisomerase I Inhibitors KW - DNA KW - 9007-49-2 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Vaccinia -- enzymology KW - Animals KW - Humans KW - Substrate Specificity KW - Oligonucleotides -- metabolism KW - Vaccinia -- genetics KW - Isoquinolines -- pharmacology KW - Indenes -- pharmacology KW - Camptothecin -- pharmacology KW - DNA -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - DNA Topoisomerases, Type I -- genetics KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71347148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Differential+induction+of+topoisomerase+I-DNA+cleavage+complexes+by+the+indenoisoquinoline+MJ-III-65+%28NSC+706744%29+and+camptothecin%3A+base+sequence+analysis+and+activity+against+camptothecin-resistant+topoisomerases+I.&rft.au=Antony%2C+Smitha%3BJayaraman%2C+Muthusamy%3BLaco%2C+Gary%3BKohlhagen%2C+Glenda%3BKohn%2C+Kurt+W%3BCushman%2C+Mark%3BPommier%2C+Yves&rft.aulast=Antony&rft.aufirst=Smitha&rft.date=2003-11-01&rft.volume=63&rft.issue=21&rft.spage=7428&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 - 2004-01-16 N1 - Date created - 2003-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Confocal imaging of xenobiotic transport across the blood-brain barrier. AN - 71337680; 14598390 AB - The brain capillary endothelium is a formidable barrier to entry of foreign chemicals into the central nervous system (CNS). For the most part it poorly distinguishes between therapeutics and neurotoxins and thus the blood-brain barrier both protects the brain from toxic chemicals and limits our ability to treat a variety of CNS disorders. Two elements underlie the barrier function of the brain capillary endothelium: 1). a physical barrier comprised of tight junctions, which form an effective seal to intercellular diffusion, and the cells themselves, which exhibit a low rate of endocytosis, and 2). a metabolic/active barrier, comprised of specific membrane transporters expressed by the endothelial cells. We have recently developed an experimental system based on confocal microscopy to study mechanisms of transport in freshly isolated brain capillaries. Here I review studies demonstrating a major role for the ATP-driven, xenobiotic export pump, p-glycoprotein, in barrier function and recent experiments showing that transient inhibition of pump function can have substantial benefit for chemotherapy in an animal model of brain cancer. Copyright 2003 Wiley-Liss, Inc. JF - Journal of experimental zoology. Part A, Comparative experimental biology AU - Miller, David S AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. miller@niehs.nih.gov Y1 - 2003/11/01/ PY - 2003 DA - 2003 Nov 01 SP - 84 EP - 90 VL - 300 IS - 1 SN - 1548-8969, 1548-8969 KW - P-Glycoprotein KW - 0 KW - Xenobiotics KW - Index Medicus KW - Biological Transport, Active -- physiology KW - Humans KW - Drug Therapy -- methods KW - Xenobiotics -- pharmacokinetics KW - P-Glycoprotein -- metabolism KW - Blood-Brain Barrier -- metabolism KW - Blood-Brain Barrier -- physiology KW - Microscopy, Confocal -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71337680?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+zoology.+Part+A%2C+Comparative+experimental+biology&rft.atitle=Confocal+imaging+of+xenobiotic+transport+across+the+blood-brain+barrier.&rft.au=Miller%2C+David+S&rft.aulast=Miller&rft.aufirst=David&rft.date=2003-11-01&rft.volume=300&rft.issue=1&rft.spage=84&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+zoology.+Part+A%2C+Comparative+experimental+biology&rft.issn=15488969&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-21 N1 - Date created - 2003-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative stress-related mechanisms are associated with xenobiotics exerting excess toxicity to Fanconi anemia cells. AN - 71336320; 14594617 AB - An extensive body of evidence has demonstrated the sensitivity of Fanconi anemia (FA) cells to redox-active xenobiotics, such as mitomycin C, diepoxybutane, cisplatin, and 8-methoxypsoralen plus ultraviolet irradiation, with toxicity mechanisms that are consistent with a deficiency of FA cells in coping with oxidative stress. A recent study has reported on excess sensitivity of FA complementation A group cells to chromium VI [Cr(VI)] toxicity, by postulating that a deficiency in Cr-DNA cross-link removal by FA cells and formation of Cr(VI)-associated cross-links may be the mechanism of Cr(VI)-induced cytotoxicity. However, the report failed to demonstrate any enhanced Cr uptake or, especially, any increase in Cr-DNA adducts. Thus, well-established findings on Cr(VI)-induced oxidative stress may explain excess sensitivity of FA cells to Cr(VI) in terms of its inability to cope with the Cr(VI)-induced prooxidant state. JF - Environmental health perspectives AU - Pagano, Giovanni AU - Manini, Paola AU - Bagchi, Debasis AD - Italian National Cancer Institute, Pediatric Oncology Research Center, Mercogliano, Italy. gbpagano@tin.it Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 1699 EP - 1703 VL - 111 IS - 14 SN - 0091-6765, 0091-6765 KW - Carcinogens, Environmental KW - 0 KW - Xenobiotics KW - Chromium KW - 0R0008Q3JB KW - chromium hexavalent ion KW - 18540-29-9 KW - Index Medicus KW - Phenotype KW - Humans KW - Cell Culture Techniques KW - Fanconi Anemia -- physiopathology KW - Oxidative Stress KW - Xenobiotics -- toxicity KW - Carcinogens, Environmental -- toxicity KW - Chromium -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71336320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oxidative+stress-related+mechanisms+are+associated+with+xenobiotics+exerting+excess+toxicity+to+Fanconi+anemia+cells.&rft.au=Pagano%2C+Giovanni%3BManini%2C+Paola%3BBagchi%2C+Debasis&rft.aulast=Pagano&rft.aufirst=Giovanni&rft.date=2003-11-01&rft.volume=111&rft.issue=14&rft.spage=1699&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 - 2004-03-02 N1 - Date created - 2003-11-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1995 Feb;110(2):177-87 [7599967] Hum Genet. 1995 Jul;96(1):14-20 [7607648] Carcinogenesis. 1995 Oct;16(10):2287-93 [7586124] Blood. 1996 Feb 1;87(3):938-48 [8562965] Carcinogenesis. 1996 Jan;17(1):103-8 [8565117] Exp Cell Res. 1996 Feb 1;222(2):262-8 [8598212] Blood. 1996 Aug 1;88(3):1019-25 [8704210] Oncology. 1996 Sep-Oct;53(5):406-11 [8784476] Am J Hematol. 1996 Oct;53(2):99-110 [8892734] J Biochem Toxicol. 1995 Dec;10(6):315-21 [8934634] Free Radic Biol Med. 1997;22(3):471-8 [8981039] Br J Haematol. 1997 Feb;96(2):240-7 [9029006] Cancer Res. 1997 Jun 1;57(11):2244-51 [9187128] Mol Cell Biochem. 2001 Jun;222(1-2):173-82 [11678599] Mutagenesis. 2001 Nov;16(6):467-74 [11682636] Mutagenesis. 1997 Sep;12(5):397-403 [9379921] Mutat Res. 1998 Jan 16;397(1):37-43 [9463550] FEBS Lett. 1998 Jan 23;422(1):99-102 [9475178] Mutat Res. 1998 May 25;400(1-2):233-44 [9685658] Blood. 1998 Nov 1;92(9):3050-6 [9787138] Med Hypotheses. 1998 Sep;51(3):253-66 [9792204] Mutat Res. 1998 Nov 12;409(2):65-72 [9838922] Cell Death Differ. 1998 Nov;5(11):940-5 [9846180] Toxicol Sci. 1998 Sep;45(1):72-6 [9848113] Mol Carcinog. 1998 Dec;23(4):201-6 [9869448] Photochem Photobiol. 1999 May;69(5):566-70 [10333762] Mol Cell Biochem. 1999 Apr;194(1-2):63-70 [10391125] Science. 1964 Jul 3;145(3627):55-8 [14162693] Mol Cell Biochem. 1999 Sep;199(1-2):149-62 [10544963] Carcinogenesis. 2000 Feb;21(2):213-20 [10657960] Mutat Res. 2000 Aug 21;469(1):135-45 [10946250] Toxicology. 2000 Sep 7;150(1-3):137-46 [10996670] Cancer Causes Control. 2000 Dec;11(10):881-9 [11142522] Oncogene. 2001 Apr 5;20(15):1803-15 [11313928] Nat Med. 2001 Jul;7(7):814-20 [11433346] J Biol Chem. 2001 Sep 14;276(37):34445-52 [11457837] Pharmacol Res. 2001 Oct;44(4):317-20 [11592867] Mol Cell Biochem. 2001 Jun;222(1-2):107-18 [11678591] Mol Cell Biochem. 2001 Jun;222(1-2):149-58 [11678597] Carcinogenesis. 2002 Jan;23(1):67-72 [11756225] J Biol Chem. 2002 Jan 25;277(4):2554-61 [11707430] Pharmacol Toxicol. 2001 Nov;89(5):225-30 [11881975] Curr Top Med Chem. 2001 Dec;1(6):529-39 [11895129] Hum Exp Toxicol. 2001 Dec;20(12):651-5 [11936580] Oncogene. 2002 Apr 4;21(15):2406-12 [11948424] J Biol Chem. 2002 Apr 19;277(16):13761-70 [11827966] Bioessays. 2002 May;24(5):439-48 [12001267] Toxicology. 2002 Jun 14;175(1-3):73-82 [12049837] Hum Exp Toxicol. 2002 Feb;21(2):77-81 [12102500] Oncogene. 2002 Aug 8;21(34):5313-24 [12149652] Toxicol Lett. 2002 Oct 5;135(3):219-28 [12270680] Isr Med Assoc J. 2002 Oct;4(10):819-23 [12389351] Cancer Res. 2002 Nov 1;62(21):6246-54 [12414654] Free Radic Res. 2002 Aug;36(8):835-43 [12420741] Environ Health Perspect. 2002 Oct;110 Suppl 5:773-7 [12426130] Mutagenesis. 2002 Nov;17(6):529-38 [12435850] Free Radic Biol Med. 2002 Dec 15;33(12):1622-40 [12488131] Biochem Pharmacol. 2003 Mar 1;65(5):833-42 [12628494] Blood. 2003 May 15;101(10):3877-84 [12521994] Bioessays. 2003 Jun;25(6):589-95 [12766948] Nature. 1976 Jun 10;261(5560):494-6 [934283] Hereditas. 1977;86(2):147-50 [914646] Mutat Res. 1980 May;78(1):59-66 [6991929] Nature. 1981 Mar 12;290(5802):142-3 [7207594] Mutat Res. 1981 Oct;85(5):347-56 [7300852] Hum Genet. 1982;61(3):228-30 [6890942] FEBS Lett. 1984 Feb 13;167(1):37-41 [6321237] Hum Genet. 1985;69(1):62-5 [3967890] Hum Genet. 1985;70(3):236-42 [4018790] Cancer Res. 1986 Jul;46(7):3528-32 [3011250] Cancer Genet Cytogenet. 1986 Aug;22(4):339-45 [3731048] Biochim Biophys Acta. 1989 Dec 8;993(2-3):143-7 [2597689] Cancer Res. 1990 Feb 1;50(3):648-52 [2153443] J Invest Dermatol. 1991 Feb;96(2):255-9 [1991986] Toxicol Appl Pharmacol. 1991 Sep 1;110(2):347-54 [1891778] Am J Hematol. 1993 Feb;42(2):196-201 [8438880] Carcinogenesis. 1993 Jun;14(6):1115-20 [8389671] Carcinogenesis. 1995 Apr;16(4):735-41 [7728950] Free Radic Biol Med. 1995 Feb;18(2):321-36 [7744317] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD. AN - 71336196; 14594733 AB - Methylphenidate, the most common treatment for attention deficit hyperactivity disorder (ADHD), increases extracellular dopamine in the brain, which is associated with its reinforcing as well as its therapeutic effects. The authors evaluated variables that distinguish these two properties. The brain imaging and clinical literatures were analyzed to identify variables that contribute to the abuse liability as well as to the clinical efficacy of methylphenidate. Four variables were identified. 1) Dose--there is a threshold for methylphenidate-induced dopamine increases to be perceived as reinforcing and to produce therapeutic effects. 2) Pharmacokinetics--the reinforcing effects of methylphenidate are associated with rapid changes in serum concentrations and presumably fast dopamine increases (as achieved with intravenous injection or insufflation), whereas the therapeutic effects are associated with slowly ascending serum concentrations and presumably smoothly rising dopamine levels (as achieved with oral administration). 3) Individual differences--sensitivity to methylphenidate varies across individuals and sets a threshold for blood and brain levels required for reinforcing effects (drug liking) and for therapeutic effects (symptom reduction). 4) Context--the effects of methylphenidate are modulated by different settings in abuse (rituals of self-administration and powerful conditioning) and in clinical use (external demands of low activity and focused attention). Reinforcing effects occur when methylphenidate elicits large and fast dopamine increases that mimic those of phasic dopamine cell firing, whereas therapeutic effects occur when methylphenidate elicits slow, steady-state dopamine increases that mimic those of tonic firing. Thus, the characteristics of clinical use (low doses administered orally and titrated for therapeutic effects) constrain methylphenidate's abuse. JF - The American journal of psychiatry AU - Volkow, Nora D AU - Swanson, James M AD - National Institute on Drug Abuse/NIH, 6001 Executive Boulevard, Room 5274-MSC 9581, Bethesda, MD 20892, USA. nv29q@nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 1909 EP - 1918 VL - 160 IS - 11 SN - 0002-953X, 0002-953X KW - Delayed-Action Preparations KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Membrane Glycoproteins KW - Membrane Transport Modulators KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Methylphenidate KW - 207ZZ9QZ49 KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Abridged Index Medicus KW - Index Medicus KW - Injections, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Brain -- drug effects KW - Reinforcement (Psychology) KW - Dopamine -- physiology KW - Dopamine -- metabolism KW - Brain -- metabolism KW - Brain -- physiology KW - Self Medication -- psychology KW - Membrane Transport Proteins -- antagonists & inhibitors KW - Extracellular Space -- metabolism KW - Treatment Outcome KW - Membrane Transport Proteins -- drug effects KW - Cocaine -- pharmacokinetics KW - Dopamine -- blood KW - Membrane Transport Proteins -- metabolism KW - Extracellular Space -- drug effects KW - Attention Deficit Disorder with Hyperactivity -- psychology KW - Substance-Related Disorders -- blood KW - Methylphenidate -- adverse effects KW - Substance-Related Disorders -- etiology KW - Methylphenidate -- therapeutic use KW - Methylphenidate -- pharmacokinetics KW - Substance-Related Disorders -- metabolism KW - Attention Deficit Disorder with Hyperactivity -- metabolism KW - Attention Deficit Disorder with Hyperactivity -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71336196?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3A&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Adolescent+Health&rft.atitle=Risk+factors+for+substance+misuse+and+adolescents%27+symptoms+of+depression&rft.au=Siennick%2C+Sonja+E.%3BWiddowson%2C+Alex+O.%3BWoessner%2C+Mathew+K.%3BFeinberg%2C+Mark+E.%3BSpoth%2C+Richard+L.&rft.aulast=Siennick&rft.aufirst=Sonja&rft.date=2016-10-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+Adolescent+Health&rft.issn=1054139X&rft_id=info:doi/10.1016%2Fj.jadohealth.2016.08.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-29 N1 - Date created - 2003-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cross-sectional volumetric analysis of brain atrophy in alcohol dependence: effects of drinking history and comorbid substance use disorder. AN - 71334784; 14594753 AB - The authors assessed whether individual differences in drinking history as well as lifetime incidence of comorbid cocaine or marijuana use disorder underlie differential patterns of brain atrophy in subjects with alcohol dependence. Segmented magnetic resonance images were used to compare whole brain cerebral gray matter and white matter in 134 male subjects age 30-50 with alcohol dependence, either alone or with comorbid cocaine or marijuana use disorder. Across all subjects, drinking history variables correlated negatively with both gray matter and white matter after age was controlled. Alcohol-dependent subjects with no comorbid substance use disorder (N=51) showed a steeper negative correlation between age and the gray matter/white matter ratio than did alcohol-dependent subjects with a comorbid lifetime cocaine use disorder diagnosis (N=50). Alcohol-dependent subjects with comorbid cocaine use disorder tended to have a steeper negative correlation between age and white matter (adjusted for intracranial volume) than did alcohol-dependent subjects with no comorbid substance use disorder. After age and the greater estimated cumulative alcohol consumption of alcohol-dependent subjects with comorbid cocaine use disorder were controlled in a multiple regression analysis, however, comorbid cocaine use disorder did not account for any independent variance in any volumetric measure. Brain atrophy among subjects with alcohol dependence reflects individual differences in exposure to alcohol, and the data provide mixed evidence that comorbid cocaine use disorder may exacerbate white matter atrophy in alcoholism. JF - The American journal of psychiatry AU - Bjork, James M AU - Grant, Steven J AU - Hommer, Daniel W AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism/NIH, 10 Center Drive, Room 3C-103, Bethesda, MD 20892, USA. jbjork@mail.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 2038 EP - 2045 VL - 160 IS - 11 SN - 0002-953X, 0002-953X KW - Abridged Index Medicus KW - Index Medicus KW - Marijuana Smoking -- pathology KW - Cocaine-Related Disorders -- diagnosis KW - Age Factors KW - Humans KW - Marijuana Smoking -- epidemiology KW - Diagnosis, Dual (Psychiatry) KW - Cocaine-Related Disorders -- epidemiology KW - Comorbidity KW - Cross-Sectional Studies KW - Cocaine-Related Disorders -- pathology KW - Adult KW - Middle Aged KW - Atrophy KW - Chronic Disease KW - Male KW - Magnetic Resonance Imaging KW - Substance-Related Disorders -- diagnosis KW - Alcohol Drinking -- pathology KW - Alcoholism -- pathology KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Substance-Related Disorders -- pathology KW - Brain -- pathology KW - Brain -- anatomy & histology KW - Alcohol Drinking -- psychology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71334784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Cross-sectional+volumetric+analysis+of+brain+atrophy+in+alcohol+dependence%3A+effects+of+drinking+history+and+comorbid+substance+use+disorder.&rft.au=Bjork%2C+James+M%3BGrant%2C+Steven+J%3BHommer%2C+Daniel+W&rft.aulast=Bjork&rft.aufirst=James&rft.date=2003-11-01&rft.volume=160&rft.issue=11&rft.spage=2038&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-29 N1 - Date created - 2003-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The emergence and characterization of macrophage-tropic SIV/HIV chimeric viruses (SHIVs) present in CD4+ T cell-depleted rhesus monkeys. AN - 71333378; 14595005 AB - Highly pathogenic simian immunodeficiency virus/human immunodeficiency virus type 1 chimeric viruses (SHIVs) induce an extremely rapid, systemic, and irreversible depletion of CD4+ T lymphocytes following their inoculation into rhesus macaques. Confocal fluorescence microscopy was used to demonstrate that high levels of viremia in infected animals were sustained by virus-producing tissue macrophage (mphi) following the irreversible elimination of CD4+ T lymphocytes by highly pathogenic SHIVDH12R. The envelope glycoproteins carried by plasma virus in CD4-depleted animals were found to contain specific alterations affecting the V2 region of gp120; similar V2 changes were observed during independent monkey infections. The altered V2 loops contained double amino acid deletions and the loss of a highly conserved N-linked glycosylation site. In contrast to the starting highly pathogenic SHIV, which is exclusively T cell-tropic, some mphi-phase SHIVs, bearing altered V2 regions, were able to establish spreading infections of cultured alveolar mphi. JF - Journal of leukocyte biology AU - Igarashi, Tatsuhiko AU - Imamichi, Hiromi AU - Brown, Charles R AU - Hirsch, Vanessa M AU - Martin, Malcolm A AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 772 EP - 780 VL - 74 IS - 5 SN - 0741-5400, 0741-5400 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD8 KW - Viral Proteins KW - Index Medicus KW - Viral Proteins -- genetics KW - Animals KW - Viral Proteins -- chemistry KW - Amino Acid Sequence KW - Genome, Viral KW - Antibodies, Monoclonal -- pharmacology KW - Mutagenesis, Site-Directed KW - Viral Load KW - Chimera KW - Sequence Alignment KW - Molecular Sequence Data KW - Macaca mulatta KW - Sequence Homology, Amino Acid KW - Antigens, CD8 -- immunology KW - Simian Immunodeficiency Virus -- genetics KW - Simian Immunodeficiency Virus -- physiology KW - Simian Immunodeficiency Virus -- isolation & purification KW - HIV -- physiology KW - Macrophages -- immunology KW - Lymphocyte Depletion KW - Macrophages -- virology KW - HIV -- isolation & purification KW - Virus Replication -- physiology KW - T-Lymphocytes -- virology KW - HIV -- genetics KW - T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71333378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+leukocyte+biology&rft.atitle=The+emergence+and+characterization+of+macrophage-tropic+SIV%2FHIV+chimeric+viruses+%28SHIVs%29+present+in+CD4%2B+T+cell-depleted+rhesus+monkeys.&rft.au=Igarashi%2C+Tatsuhiko%3BImamichi%2C+Hiromi%3BBrown%2C+Charles+R%3BHirsch%2C+Vanessa+M%3BMartin%2C+Malcolm+A&rft.aulast=Igarashi&rft.aufirst=Tatsuhiko&rft.date=2003-11-01&rft.volume=74&rft.issue=5&rft.spage=772&rft.isbn=&rft.btitle=&rft.title=Journal+of+leukocyte+biology&rft.issn=07415400&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-09 N1 - Date created - 2003-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Signal pathway profiling of prostate cancer using reverse phase protein arrays. AN - 71328715; 14595813 AB - Reverse phase protein arrays represent a new proteomics microarray technology with which to study the fluctuating state of the proteome in minute quantities of cells. The activation status of cell signaling pathways controls cellular fate and deregulation of these pathways underpins carcinogenesis. Changes in pathway activation that occur between early stage prostatic epithelial lesions, prostatic stroma and the extracellular matrix can be analyzed by obtaining pure populations of cell types by laser capture microdissection (LCM) and analyzing the relative states of several key phosphorylation points within the cellular circuitry. We have applied reverse phase protein array technology to analyze the status of key points in cell signaling involved in pro-survival, mitogenic, apoptotic and growth regulation pathways in the progression from normal prostate epithelium to invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled with LCM, the states of signaling changes during disease progression from prostate cancer study sets were analyzed. Focused analysis of phospho-specific endpoints revealed changes in cellular signaling events through disease progression and between patients. We have used a new protein array technology to study specific molecular pathways believed to be important in cell survival and progression from normal epithelium to invasive carcinoma directly from human tissue specimens. With the advent of molecular targeted therapeutics, the identification, characterization and monitoring of the signaling events within actual human biopsies will be critical for patient-tailored therapy. JF - Proteomics AU - Grubb, Robert L AU - Calvert, Valerie S AU - Wulkuhle, Julia D AU - Paweletz, Cloud P AU - Linehan, W Marston AU - Phillips, John L AU - Chuaqui, Rodrigo AU - Valasco, Alfredo AU - Gillespie, John AU - Emmert-Buck, Michael AU - Liotta, Lance A AU - Petricoin, Emanuel F AD - Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 2142 EP - 2146 VL - 3 IS - 11 SN - 1615-9853, 1615-9853 KW - Antigens, Neoplasm KW - 0 KW - Biomarkers, Tumor KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Index Medicus KW - Phosphorylation KW - Humans KW - Male KW - Prostatic Neoplasms -- metabolism KW - Signal Transduction -- physiology KW - Prostatic Neoplasms -- pathology KW - Cell Transformation, Neoplastic -- pathology KW - Cell Transformation, Neoplastic -- metabolism KW - Prostate -- metabolism KW - Antigens, Neoplasm -- metabolism KW - Prostate -- pathology KW - Prostatic Intraepithelial Neoplasia -- pathology KW - Antigens, Neoplasm -- immunology KW - Prostatic Intraepithelial Neoplasia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71328715?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteomics&rft.atitle=Signal+pathway+profiling+of+prostate+cancer+using+reverse+phase+protein+arrays.&rft.au=Grubb%2C+Robert+L%3BCalvert%2C+Valerie+S%3BWulkuhle%2C+Julia+D%3BPaweletz%2C+Cloud+P%3BLinehan%2C+W+Marston%3BPhillips%2C+John+L%3BChuaqui%2C+Rodrigo%3BValasco%2C+Alfredo%3BGillespie%2C+John%3BEmmert-Buck%2C+Michael%3BLiotta%2C+Lance+A%3BPetricoin%2C+Emanuel+F&rft.aulast=Grubb&rft.aufirst=Robert&rft.date=2003-11-01&rft.volume=3&rft.issue=11&rft.spage=2142&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-05 N1 - Date created - 2003-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The fragile X syndrome repeats form RNA hairpins that do not activate the interferon-inducible protein kinase, PKR, but are cut by Dicer. AN - 71327763; 14576312 AB - We show here that under physiologically reasonable conditions, CGG repeats in RNA readily form hairpins. In contrast to its DNA counterpart that forms a complex mixture of hairpins and tetraplexes, r(CGG)22 forms a single stable hairpin with no evidence for any other folded structure even at low pH. RNA with the sequence (CGG)9AGG (CGG)12AGG(CGG)97, found in a fragile X syndrome pre-mutation allele, forms a number of different hairpins. The most prominent hairpin forms in the 3' part of the repeat and involves the 97 uninterrupted CGG repeats. In contrast to the CUG-RNA hairpins formed by myotonic dystrophy type 1 repeats, we found no evidence that CGG-RNA hairpins activate PKR, the interferon-inducible protein kinase that is activated by a wide range of double-stranded RNAs. However, we do show that the CGG-RNA is digested, albeit inefficiently, by the human Dicer enzyme, a step central to the RNA interference effect on gene expression. These data provide clues to the basis of the toxic effect of CGG-RNA that is thought to occur in fragile X pre-mutation carriers. In addition, RNA hairpins may also account for the stalling of the 40S ribosomal subunit that is thought to contribute to the translation deficit in fragile X pre-mutation and full mutation alleles. JF - Nucleic acids research AU - Handa, Vaishali AU - Saha, Tapas AU - Usdin, Karen AD - Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA. Y1 - 2003/11/01/ PY - 2003 DA - 2003 Nov 01 SP - 6243 EP - 6248 VL - 31 IS - 21 KW - RNA KW - 63231-63-0 KW - eIF-2 Kinase KW - EC 2.7.11.1 KW - Ribonuclease III KW - EC 3.1.26.3 KW - Index Medicus KW - Base Sequence KW - Alleles KW - Thermodynamics KW - Enzyme Activation KW - Humans KW - RNA Stability KW - Mutation -- genetics KW - Substrate Specificity KW - Cell Line KW - eIF-2 Kinase -- metabolism KW - RNA -- metabolism KW - Fragile X Syndrome -- genetics KW - Ribonuclease III -- metabolism KW - Trinucleotide Repeats -- genetics KW - RNA -- chemistry KW - Nucleic Acid Conformation KW - RNA -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71327763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+fragile+X+syndrome+repeats+form+RNA+hairpins+that+do+not+activate+the+interferon-inducible+protein+kinase%2C+PKR%2C+but+are+cut+by+Dicer.&rft.au=Handa%2C+Vaishali%3BSaha%2C+Tapas%3BUsdin%2C+Karen&rft.aulast=Handa&rft.aufirst=Vaishali&rft.date=2003-11-01&rft.volume=31&rft.issue=21&rft.spage=6243&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 - 2003-12-09 N1 - Date created - 2003-10-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: RNA. 2000 Jan;6(1):79-87 [10668800] Am J Med Genet. 1999 Apr 2;83(4):322-5 [10208170] Biochem Biophys Res Commun. 2001 Jun 15;284(3):798-807 [11396973] Am J Med Genet. 2000 Fall;97(3):189-94 [11449487] Curr Opin Genet Dev. 2002 Jun;12(3):266-71 [12076668] Brain. 2002 Aug;125(Pt 8):1760-71 [12135967] Nucleic Acids Res. 2003 Jul 1;31(13):3406-15 [12824337] Proc Natl Acad Sci U S A. 1990 Nov;87(22):8687-91 [2247437] Cell. 1991 May 31;65(5):905-14 [1710175] J Virol. 1991 Nov;65(11):5657-62 [1920611] Cell. 1991 Dec 20;67(6):1047-58 [1760838] Proc Natl Acad Sci U S A. 1994 May 24;91(11):4950-4 [8197163] Biochemistry. 1995 Oct 3;34(39):12803-11 [7548035] Nucleic Acids Res. 1995 Oct 25;23(20):4202-9 [7479085] J Biol Chem. 1995 Dec 1;270(48):28970-7 [7499428] J Mol Biol. 1995 Dec 8;254(4):638-56 [7500339] J Biol Chem. 1997 Dec 5;272(49):31079-85 [9388259] Biochemistry. 1998 May 5;37(18):6303-16 [9572845] Genomics. 1998 Jun 1;50(2):229-40 [9653650] J Theor Biol. 1998 Jun 21;192(4):505-14 [9680723] Nucleic Acids Res. 1998 Sep 1;26(17):4078-85 [9705522] Anal Biochem. 1999 Feb 1;267(1):241-3 [9918680] Biochem Biophys Res Commun. 2000 Nov 30;278(3):833-8 [11095993] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of diet and animal care/housing protocols on body weight, survival, tumor incidences, and nephropathy severity of F344 rats in chronic studies. AN - 71326122; 14585736 AB - Diet is an important environmental factor affecting body weight, survival, and age-related diseases of rodents. The NIH-07 open formula diet was the diet used in the National Toxicology Program's (NTPs) rodent carcinogenicity studies from 1980 to 1994. In 1994 the NTP began using a new diet designated the NTP-2000 diet. This paper compares body weight, survival, tumor incidence, and nephropathy severity in untreated control groups of Fischer 344 (F344) rats fed the NTP-2000 or NIH-07 diets, using data from 22 separate 2-year feed and inhalation studies. The feed studies were conducted in 3 different facilities, and all the inhalation studies were conducted in a single facility. During feed studies, rats were group housed in polycarbonate cages and fed diets in powder (mash) form, while in inhalation studies, rats were housed individually in wire mesh cages, and fed diets in pelleted form. Survival was significantly (p<0.05) higher in groups fed NTP-2000 diet compared to the corresponding groups fed NIH-07 diet, irrespective of sex or housing conditions. Use of the NTP-2000 diet was also associated with a decreased incidence of pituitary gland tumors in both sexes and decreased incidences of adrenal pheochromocytoma and preputial gland tumors in males. The incidence and severity of nephropathy was also decreased in animals receiving the NTP-2000 diet, especially males. The decreased nephropathy severity and the decreased incidence of pituitary gland tumors are likely the major factors contributing to the improved survival of rats receiving the NTP-2000 diet relative to those given the NIH-07 diet. These data also support earlier findings that decreased incidences of adrenal pheochromocytoma are associated with reduced nephropathy severity in male F344 rats. Throughout the two-year study female rats receiving the NTP-2000 diet were significantly (p<0.05) lighter than those receiving the NIH-07 diet. However, it is uncertain if this difference can be attributed to the NTP-2000 diet, since implementation of this diet by the NTP approximately coincided with changes in the F344 rat production colony that resulted in somewhat lighter animals being provided to the NTP. Controls from inhalation studies and feed studies differed significantly (p<0.01) in the incidence of a variety of tumors, irrespective of diet. This suggests that differences in animal care and housing protocols may impact tumor incidence in F344 rats, most notably pituitary gland and testis tumors. JF - Toxicologic pathology AU - Haseman, Joseph K AU - Ney, Elizabeth AU - Nyska, Abraham AU - Rao, Ghanta N AD - Biostatistics Branch, Environmental Diseases and Medicine Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. haseman@niehs.nih.gov PY - 2003 SP - 674 EP - 681 VL - 31 IS - 6 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Rats KW - Food, Formulated -- analysis KW - Animals KW - Rats, Inbred F344 KW - Housing, Animal KW - Male KW - Female KW - Kidney Diseases -- pathology KW - Toxicity Tests, Chronic -- methods KW - Neoplasms -- pathology KW - Animal Husbandry -- methods KW - Longevity -- physiology KW - Neoplasms -- epidemiology KW - Body Weight -- physiology KW - Animal Feed -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71326122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Effect+of+diet+and+animal+care%2Fhousing+protocols+on+body+weight%2C+survival%2C+tumor+incidences%2C+and+nephropathy+severity+of+F344+rats+in+chronic+studies.&rft.au=Haseman%2C+Joseph+K%3BNey%2C+Elizabeth%3BNyska%2C+Abraham%3BRao%2C+Ghanta+N&rft.aulast=Haseman&rft.aufirst=Joseph&rft.date=2003-11-01&rft.volume=31&rft.issue=6&rft.spage=674&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-27 N1 - Date created - 2003-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fenretinide: a prototype cancer prevention drug. AN - 71322589; 14585058 AB - Fenretinide (N-4-hydroxyphenylretinamide [4-HPR]) is a synthetic retinoid that has been examined in in vitro assays, preclinical animal models and clinical trials as a cancer chemopreventive agent. Its pharmacology, toxicity and mechanisms of action initially suggested an increased therapeutic index relative to native retinoids for the control of tumours of the breast, prostate, bladder, colon, cervix and head and neck. Although fenretinide at the doses and schedules used in several pivotal Phase II and III clinical trials has not been proven to be efficacious in reducing the incidence of cancer or in retarding the development of preneoplastic lesions, encouraging observations regarding unanticipated preventative activity, such as for ovarian cancer control, have arisen from these studies. Research in cancer therapy and the elucidation of molecular pathways activated by fenretinide have also yielded clues about how this agent might be better used in a prevention setting. Current trials are underway to re-examine both dose and schedule of fenretinide administration as well as the target tissues of interest. Investigations of potential synergism between fenretinide and other candidate chemopreventative molecules with complementary mechanisms of action may support future assessments of this prototype cancer prevention drug or its newer analogues. JF - Expert opinion on investigational drugs AU - Malone, Winfred AU - Perloff, Marjorie AU - Crowell, James AU - Sigman, Caroline AU - Higley, Howard AD - National Cancer Institute, Division of Cancer Prevention, Chemopreventive Agent Development Research Group, Bethesda, MD, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 1829 EP - 1842 VL - 12 IS - 11 SN - 1354-3784, 1354-3784 KW - Anticarcinogenic Agents KW - 0 KW - Fenretinide KW - 187EJ7QEXL KW - Index Medicus KW - Animals KW - Humans KW - Precancerous Conditions -- prevention & control KW - Clinical Trials as Topic KW - Drug Evaluation, Preclinical KW - Fenretinide -- adverse effects KW - Fenretinide -- therapeutic use KW - Anticarcinogenic Agents -- therapeutic use KW - Fenretinide -- pharmacology KW - Anticarcinogenic Agents -- pharmacology KW - Neoplasms -- prevention & control KW - Anticarcinogenic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71322589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Fenretinide%3A+a+prototype+cancer+prevention+drug.&rft.au=Malone%2C+Winfred%3BPerloff%2C+Marjorie%3BCrowell%2C+James%3BSigman%2C+Caroline%3BHigley%2C+Howard&rft.aulast=Malone&rft.aufirst=Winfred&rft.date=2003-11-01&rft.volume=12&rft.issue=11&rft.spage=1829&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 - 2004-03-18 N1 - Date created - 2003-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetics of adrenocortical tumors: gatekeepers, landscapers and conductors in symphony. AN - 71313795; 14580759 AB - The genetic and histopathological backgrounds of adrenocortical tumorigenesis remain poorly characterized. In other tissues, there is conclusive evidence that hyperplasia and adenomas precede cancer. In the adrenal, there are few clinical cases of either hyperplasia or adenoma associated with later development of cancer, and there are few biological studies that attempt to characterize this process molecularly. Current research focuses on the early lesions of the adrenal cortex because of their possible molecular link with carcinogenesis, and evidence of their frequent association with atypical forms of Cushing's and Conn's syndromes, obesity, hypertension and/or diabetes. These studies indicate a model for oncogenesis that is the same as that in other tissues. The rarity of adrenal cancer compared to benign lesions could be a clue to unique features of adrenocortical cells. It might also highlight the function of genes that are associated with endocrine tumors in the context of which the concept of gene 'conductors' is introduced here. JF - Trends in endocrinology and metabolism: TEM AU - Stratakis, Constantine A AD - Section on Endocrinology and Genetics, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1862, USA. stratakc@mail.nichd.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 404 EP - 410 VL - 14 IS - 9 SN - 1043-2760, 1043-2760 KW - Cyclic AMP-Dependent Protein Kinase RIalpha Subunit KW - 0 KW - PRKAR1A protein, human KW - Proteins KW - Receptors, Steroid KW - Inhibins KW - 57285-09-3 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Inhibins -- genetics KW - Hyperplasia KW - Genes, Tumor Suppressor KW - Humans KW - Genes, p53 -- genetics KW - Receptors, Steroid -- genetics KW - Proteins -- genetics KW - Mutation KW - Female KW - Cushing Syndrome -- genetics KW - Adrenocortical Carcinoma -- genetics KW - Adrenal Cortex -- pathology KW - Gene Expression Regulation, Neoplastic -- physiology KW - Adrenal Cortex Neoplasms -- genetics KW - Adrenocortical Adenoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71313795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+endocrinology+and+metabolism%3A+TEM&rft.atitle=Genetics+of+adrenocortical+tumors%3A+gatekeepers%2C+landscapers+and+conductors+in+symphony.&rft.au=Stratakis%2C+Constantine+A&rft.aulast=Stratakis&rft.aufirst=Constantine&rft.date=2003-11-01&rft.volume=14&rft.issue=9&rft.spage=404&rft.isbn=&rft.btitle=&rft.title=Trends+in+endocrinology+and+metabolism%3A+TEM&rft.issn=10432760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-28 N1 - Date created - 2003-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study. AN - 71312015; 14581418 AB - To describe the clinical features and outcome of HIV-associated primary effusion lymphoma (PEL) and to compare them with those of the other HIV-associated non-Hodgkin's lymphomas (NHLs). From April 1987 to June 2002, 277 patients with HIV infection and systemic NHL were diagnosed and treated in our institution. Clinical features and outcome of PEL patients were compared with the features and outcomes of 162 patients belonging to the following histologic subtypes: plasmoblastic lymphoma of oral cavity (PBLOC, n = 11), immunoblastic lymphoma (IBL, n = 76), and centroblastic B-cell lymphoma (CBCL, n = 75). Among the 277 NHL patients, PEL was diagnosed in 11 patients (4%). Eight of 11 patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimen. Complete remission was reached in 42% of patients, with a median survival time of 6 months. When the clinical features and outcome of 11 PEL patients were compared with the other three groups of patients affected by NHL, at the onset of the disease, no statistically significant differences were observed in demographic data, CD4 absolute number, HIV viremia plasma levels, and clinical characteristics. When we compared the outcome of PEL patients with the CBCL group, a statistically significant worse outcome was observed; however, the clinical outcome of PEL patients was not significantly different from the outcome observed in the other two groups (PBLOC and IBL groups). PEL is a rare HIV-associated NHL type occurring as a late manifestation of HIV infection with a poor clinical outcome and a shorter overall survival compared with CBCL patients. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Simonelli, Cecelia AU - Spina, Michele AU - Cinelli, Roberta AU - Talamini, Renato AU - Tedeschi, Rosamaria AU - Gloghini, Annunziata AU - Vaccher, Emanuela AU - Carbone, Antonio AU - Tirelli, Umberto AD - Division of medical Oncology A, National Cancer Institute, Aviano, Italy. Y1 - 2003/11/01/ PY - 2003 DA - 2003 Nov 01 SP - 3948 EP - 3954 VL - 21 IS - 21 SN - 0732-183X, 0732-183X KW - Vincristine KW - 5J49Q6B70F KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Medical Records KW - Humans KW - Vincristine -- administration & dosage KW - Retrospective Studies KW - Doxorubicin -- administration & dosage KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Italy -- epidemiology KW - Female KW - Male KW - Prednisone -- administration & dosage KW - Survival Analysis KW - Lymphoma, Non-Hodgkin -- epidemiology KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Lymphoma, Non-Hodgkin -- mortality KW - HIV Infections KW - Antiretroviral Therapy, Highly Active KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Lymphoma, Non-Hodgkin -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71312015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Clinical+features+and+outcome+of+primary+effusion+lymphoma+in+HIV-infected+patients%3A+a+single-institution+study.&rft.au=Simonelli%2C+Cecelia%3BSpina%2C+Michele%3BCinelli%2C+Roberta%3BTalamini%2C+Renato%3BTedeschi%2C+Rosamaria%3BGloghini%2C+Annunziata%3BVaccher%2C+Emanuela%3BCarbone%2C+Antonio%3BTirelli%2C+Umberto&rft.aulast=Simonelli&rft.aufirst=Cecelia&rft.date=2003-11-01&rft.volume=21&rft.issue=21&rft.spage=3948&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 - 2003-11-20 N1 - Date created - 2003-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The epidemiology of alcohol-induced pancreatitis. AN - 71305579; 14576488 AB - Although the association between alcohol and pancreatitis has been recognized for centuries, the precise magnitude of the impact of alcohol remains poorly quantified. Epidemiologic research on this condition has been seriously handicapped by several factors. Classifications are based on morphology rather than on etiology; the diagnostic differences between acute and chronic pancreatitis are imprecise and confusing; and coding by the International Classification of Diseases (ICD) has been inadequate. The current ICD (ICD-10), used in the United States since 1999, identifies alcohol-induced chronic pancreatitis as a separate code for the first time, an enhancement that will greatly improve the quality of data collected in current and future studies. Unfortunately, no code yet exists for acute alcoholic pancreatitis. Of the approximately 2.4 million deaths in the United States in 1999, pancreatitis was listed as the underlying cause for 3289 deaths, making it the 235th leading cause of death. Acute pancreatitis accounted for 84% of these deaths, and chronic pancreatitis the remaining 16%. Alcohol is a primary cause of both acute and chronic pancreatitis in most developed countries. About one-third of acute pancreatitis in the United States is alcohol-induced. In the United States and other developed countries, 60%-90% of chronic pancreatitis is alcohol induced. Both forms are more common in men. The development of chronic pancreatitis is proportional to the dose and duration of alcohol consumption (minimum, 6-12 years of approximately 80 g of alcohol per day). Autopsy studies reveal subclinical chronic pancreatitis in another 10% of alcohol abusers. Yet, since <10% of chronic alcoholics develop chronic pancreatitis, clearly other predisposing factors besides alcohol are involved. Genetic variability and environmental exposures, such as diet, are prime candidates for further investigation. To date, there have been few large epidemiological studies of alcoholic pancreatitis in the United States or other developed countries. Additional studies are needed to improve the quality of existing baseline epidemiologic data and allow better assessment of risk. Improved diagnostic precision, more complete and specific coding, and greater understanding of covariables and mechanisms would also advance the field. JF - Pancreas AU - Dufour, Mary C AU - Adamson, Megan D AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-7003, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 286 EP - 290 VL - 27 IS - 4 KW - Index Medicus KW - Acute Disease KW - Risk Factors KW - Pancreatitis -- epidemiology KW - Humans KW - Adult KW - Incidence KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Female KW - Pancreatitis, Alcoholic -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71305579?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3A&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Abnormal+Child+Psychology&rft.atitle=Early+adolescent+growth+in+depression+and+conduct+problem+symptoms+as+predictors+of+later+substance+use+impairment&rft.au=McCarty%2C+Carolyn+A.%3BWymbs%2C+Brian+T.%3BMason%2C+W.+Alex%3BKing%2C+Kevin+M.%3BMcCauley%2C+Elizabeth%3BBaer%2C+John%3BVander+Stoep%2C+Ann&rft.aulast=McCarty&rft.aufirst=Carolyn&rft.date=2013-10-01&rft.volume=41&rft.issue=7&rft.spage=1041&rft.isbn=&rft.btitle=&rft.title=Journal+of+Abnormal+Child+Psychology&rft.issn=00910627&rft_id=info:doi/10.1007%2Fs10802-013-9752-x LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-15 N1 - Date created - 2003-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The graft-versus-leukemia effect of nonmyeloablative stem cell allografts may not be sufficient to cure chronic myelogenous leukemia. AN - 71305556; 14561990 AB - We treated 12 patients with chronic myelogenous leukemia (CML) with a low-intensity preparative regimen followed by allogeneic stem cell transplantation in an attempt to confer a curative graft-versus-leukemia (GVL) effect with minimum morbidity. Seven patients in first chronic phase (CP1) and five in second chronic phase (CP2) (age 15-68 years) received a nonmyeloablative conditioning regimen of fludarabine and cyclophosphamide, followed by a G-CSF-mobilized peripheral blood stem cell (PBSC) transplant from an HLA-identical sibling. Cyclosporine (CsA) was used for graft-versus-host disease (GVHD) prophylaxis. Median follow-up was 384 days. Neutrophil recovery occurred at a median of 12 days. There was no transplant-related mortality. Of the seven CP1 patients transplanted, seven achieved a stable molecular remission; two with no post-transplant intervention, three after donor lymphocytes, imatinib and interferon, and two after a myeloablative stem cell transplant. Four of five CP2 patients died in blast crisis and one survived in molecular remission. Of the 12 patients with durable engraftment, six had Grades II-IV acute GVHD; six had limited chronic GVHD. These results suggest that cytoreduction is required to optimize the curative effect of allogeneic stem cell transplantation for CML. JF - Bone marrow transplantation AU - Sloand, E AU - Childs, R W AU - Solomon, S AU - Greene, A AU - Young, N S AU - Barrett, A J AD - Stem Cell Allotransplantation Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 897 EP - 901 VL - 32 IS - 9 SN - 0268-3369, 0268-3369 KW - Cyclophosphamide KW - 8N3DW7272P KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Humans KW - Leukemia, Myeloid, Chronic-Phase -- mortality KW - Transplantation, Isogeneic KW - Aged KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Transplantation, Homologous KW - Graft vs Host Disease -- prevention & control KW - Leukemia, Myeloid, Chronic-Phase -- therapy KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Vidarabine -- analogs & derivatives KW - Peripheral Blood Stem Cell Transplantation -- mortality KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- mortality KW - Transplantation Conditioning -- methods KW - Vidarabine -- administration & dosage KW - Peripheral Blood Stem Cell Transplantation -- methods KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- therapy KW - Graft vs Leukemia Effect -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71305556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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%3A+Clinical+and+Experimental+Research&rft.atitle=Longitudinal+associations+between+alcohol+problems+and+depressive+symptoms%3A+Early+adolescence+through+early+adulthood&rft.au=Marmorstein%2C+Naomi+R.&rft.aulast=Marmorstein&rft.aufirst=Naomi&rft.date=2009-01-01&rft.volume=33&rft.issue=1&rft.spage=49&rft.isbn=&rft.btitle=&rft.title=Alcoholism%3A+Clinical+and+Experimental+Research&rft.issn=01456008&rft_id=info:doi/10.1111%2Fj.1530-0277.2008.00810.x LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-08 N1 - Date created - 2003-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Importance of amino acids of the central portion of the second intracellular loop of the gastrin-releasing Peptide receptor for phospholipase C activation, internalization, and chronic down-regulation. AN - 71301377; 12970386 AB - Little is known about the function of the central portion of the second intracellular loop (i2 loop) of peptide receptors in activation of downstream pathways and receptor modulatory processes such as receptor internalization or chronic down-regulation (DR). Recent data suggest a role for i2 loop hydrophobic amino acids in these processes. We used site-directed mutagenesis to address these issues with the gastrin-releasing peptide receptor (GRP-R). Each i2 loop residue from 142 to 148 was mutated and the receptors were expressed in Balb 3T3 cells. Two mutants showed a minimal (<2-fold) decrease in affinity. Five mutants showed decreased efficacy for activating phospholipase C (PLC). Two double mutants (IM143.147AA and VM144.147AA) showed a minimal decrease in affinity but had a decreased ability to fully activate PLC. Only the IM double mutation had decreased maximal internalization, whereas the R145A single mutant showed an increase, suggesting a tonic inhibitory role for Arg-145 in internalization. Three single and both double mutants showed decreases in receptor DR. There was a weak correlation between the extent of GRP-R internalization and the maximal PLC activation, whereas changes in the maximal PLC activation were significantly (p = 0.008) coupled to receptor DR. This study shows that amino acids of the i2 loop of the GRP-R are important in activation of PLC, internalization and down-regulation, but not for affinity. Our results support the proposal that internalization and chronic down-regulation have differing dependence on PLC and are largely independent processes, because some mutants showed no changes in internalization, but significant alterations in down-regulation. JF - The Journal of pharmacology and experimental therapeutics AU - Schumann, Michael AU - Nakagawa, Tomoo AU - Mantey, Samuel A AU - Tokita, Kenji AU - Venzon, David J AU - Hocart, Simon J AU - Benya, Richard V AU - Jensen, Robert T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Rm. 9C-103, 10 Center Drive, MSC 1804, Bethesda, MD 20892, USA. robertj@bdg10.niddk.nih.gov Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 597 EP - 607 VL - 307 IS - 2 SN - 0022-3565, 0022-3565 KW - Amino Acids KW - 0 KW - Receptors, Bombesin KW - Gastrin-Releasing Peptide KW - 80043-53-4 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Index Medicus KW - Animals KW - Gastrin-Releasing Peptide -- metabolism KW - Enzyme Activation KW - Humans KW - Amino Acid Sequence KW - Mice KW - Mice, Inbred BALB C KW - BALB 3T3 Cells KW - Down-Regulation KW - Transfection KW - Molecular Sequence Data KW - Cell Membrane -- metabolism KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Receptors, Bombesin -- genetics KW - Receptors, Bombesin -- metabolism KW - Type C Phospholipases -- metabolism KW - Receptors, Bombesin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71301377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Importance+of+amino+acids+of+the+central+portion+of+the+second+intracellular+loop+of+the+gastrin-releasing+Peptide+receptor+for+phospholipase+C+activation%2C+internalization%2C+and+chronic+down-regulation.&rft.au=Schumann%2C+Michael%3BNakagawa%2C+Tomoo%3BMantey%2C+Samuel+A%3BTokita%2C+Kenji%3BVenzon%2C+David+J%3BHocart%2C+Simon+J%3BBenya%2C+Richard+V%3BJensen%2C+Robert+T&rft.aulast=Schumann&rft.aufirst=Michael&rft.date=2003-11-01&rft.volume=307&rft.issue=2&rft.spage=597&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 - 2003-12-10 N1 - Date created - 2003-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pronounced chromosomal instability and multiple gene amplifications characterize ulcerative colitis-associated colorectal carcinomas. AN - 71301233; 14580765 AB - Patients with ulcerative colitis have a significantly increased lifetime risk for the development of colorectal carcinomas. While genetic and genomic changes during carcinogenesis have been thoroughly studied in sporadic colorectal cancers, less is known about ulcerative colitis-associated colorectal carcinomas. The aim of this study was to extend the identification of specific genomic imbalances to ulcerative colitis-associated colorectal carcinomas and to establish a comprehensive map of DNA gains and losses by investigating 23 tumor specimens from 23 patients. The molecular cytogenetic characterization was performed using comparative genomic hybridization; immunohistochemistry was used to measure proliferative activity and laminin-5 expression as a marker for invasiveness. The results indicate that these tumors are invariably aneuploid, with a high proliferative activity and increased invasive potential. The average number of copy alterations correlates with increased cyclin A levels (P=0.044), which is an independent predictor of risk of carcinoma development in ulcerative colitis. Despite severe genetic instability, the general pattern of specific chromosomal aberrations that defines sporadic colorectal carcinomas is maintained in ulcerative colitis-associated malignancies. High-level copy number increases (amplifications) are dispersed throughout the genome. Strikingly, these amplifications are much more frequent than in sporadic carcinomas and map to chromosomal regions that have not been described before. JF - Cancer genetics and cytogenetics AU - Habermann, Jens K AU - Upender, Madhvi B AU - Roblick, Uwe J AU - Krüger, Stefan AU - Freitag, Sandra AU - Blegen, Harald AU - Bruch, Hans Peter AU - Schimmelpenning, Hendrik AU - Auer, Gert AU - Ried, Thomas AD - Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 50, Room 1408, 50 South Drive, Bethesda, MD 20892-8010, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 9 EP - 17 VL - 147 IS - 1 SN - 0165-4608, 0165-4608 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Neoplasm Staging KW - Humans KW - Adenocarcinoma -- mortality KW - Adenocarcinoma -- genetics KW - Nucleic Acid Hybridization KW - Adenocarcinoma -- pathology KW - Adult KW - Allelic Imbalance -- genetics KW - DNA, Neoplasm -- genetics KW - Middle Aged KW - Time Factors KW - Adenocarcinoma -- surgery KW - Immunohistochemistry KW - Female KW - Male KW - Survival Analysis KW - Diploidy KW - Rectal Neoplasms -- mortality KW - Colitis, Ulcerative -- complications KW - Colonic Neoplasms -- genetics KW - Chromosomal Instability -- genetics KW - Colonic Neoplasms -- surgery KW - Rectal Neoplasms -- pathology KW - Rectal Neoplasms -- etiology KW - Colitis, Ulcerative -- genetics KW - Colitis, Ulcerative -- surgery KW - Gene Amplification KW - Rectal Neoplasms -- genetics KW - Rectal Neoplasms -- surgery KW - Colonic Neoplasms -- etiology KW - Colonic Neoplasms -- mortality KW - Chromosome Aberrations KW - Colitis, Ulcerative -- pathology KW - Colonic Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71301233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+genetics+and+cytogenetics&rft.atitle=Pronounced+chromosomal+instability+and+multiple+gene+amplifications+characterize+ulcerative+colitis-associated+colorectal+carcinomas.&rft.au=Habermann%2C+Jens+K%3BUpender%2C+Madhvi+B%3BRoblick%2C+Uwe+J%3BKr%C3%BCger%2C+Stefan%3BFreitag%2C+Sandra%3BBlegen%2C+Harald%3BBruch%2C+Hans+Peter%3BSchimmelpenning%2C+Hendrik%3BAuer%2C+Gert%3BRied%2C+Thomas&rft.aulast=Habermann&rft.aufirst=Jens&rft.date=2003-11-01&rft.volume=147&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Cancer+genetics+and+cytogenetics&rft.issn=01654608&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-03 N1 - Date created - 2003-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with chemotactic activities for dendritic cells. AN - 71299789; 12855582 AB - Recent publications have highlighted the chemotactic activities of antimicrobial proteins derived from the granules of neutrophils and basophils. Eosinophil granules also contain antimicrobial proteins. One of them is eosinophil-derived neurotoxin (EDN), a protein belonging to the ribonuclease A (RNase A) superfamily, which has recently been found to have antiviral activity in vitro. We found that EDN was selectively chemotactic for dendritic cells (DCs). The DC chemotactic activity of EDN was inhibited by either pretreatment of DCs with pertussis toxin or by simultaneous addition of placental RNase inhibitor to inhibit the activity of EDN. EDN was not chemotactic for leukocytes other than DCs. Mouse eosinophil-associated RNase 2 (mEAR2), one of a cluster of divergent orthologs of human EDN, was also chemotactic for human as well as mouse DCs. Sequence and mutational analysis demonstrated the importance of the N-terminal region of mEAR2 in mediating its chemotactic effect on DCs. EDN also induced the activation of p42/44 mitogen-activated protein kinase (MAPK) in DCs. Furthermore, injection of mEAR2 into the air pouches of mice resulted in the recruitment of DCs into the air pouches. Thus, EDN and its mouse ortholog, mEAR2, are eosinophil granule-derived antimicrobial RNases that function as chemoattractants for DCs in vitro and in vivo. JF - Blood AU - Yang, De AU - Rosenberg, Helene F AU - Chen, Qian AU - Dyer, Kimberly D AU - Kurosaka, Kahori AU - Oppenheim, Joost J AD - Basic Research Program, SAIC-Frederick, Laboratory of Molecular Regulation, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg 560, Rm 31-19, Frederick, MD 21702-1201, USA. dyang@mail.ncifcrf.gov Y1 - 2003/11/01/ PY - 2003 DA - 2003 Nov 01 SP - 3396 EP - 3403 VL - 102 IS - 9 SN - 0006-4971, 0006-4971 KW - Antigens, CD34 KW - 0 KW - Antiviral Agents KW - COUP Transcription Factors KW - DNA-Binding Proteins KW - Nr2f6 protein, mouse KW - Receptors, Cytoplasmic and Nuclear KW - Mitogen-Activated Protein Kinase 3 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Ear2 protein, mouse KW - EC 3.1.- KW - Eosinophil-Derived Neurotoxin KW - Ribonucleases KW - RNASE2 protein, human KW - EC 3.1.27.5 KW - GTP-Binding Protein alpha Subunits, Gi-Go KW - EC 3.6.5.1 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Mice KW - Mitogen-Activated Protein Kinases -- drug effects KW - Monocytes -- cytology KW - DNA-Binding Proteins -- physiology KW - Antiviral Agents -- physiology KW - Ribonucleases -- physiology KW - Chemotaxis, Leukocyte -- drug effects KW - Ribonucleases -- pharmacology KW - Antiviral Agents -- pharmacology KW - Dendritic Cells -- physiology KW - Dendritic Cells -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71299789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Eosinophil-derived+neurotoxin+%28EDN%29%2C+an+antimicrobial+protein+with+chemotactic+activities+for+dendritic+cells.&rft.au=Yang%2C+De%3BRosenberg%2C+Helene+F%3BChen%2C+Qian%3BDyer%2C+Kimberly+D%3BKurosaka%2C+Kahori%3BOppenheim%2C+Joost+J&rft.aulast=Yang&rft.aufirst=De&rft.date=2003-11-01&rft.volume=102&rft.issue=9&rft.spage=3396&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-05 N1 - Date created - 2003-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tgf-beta inhibits activation and uveitogenicity of primary but not of fully polarized retinal antigen-specific memory-effector T cells. AN - 71297422; 14578402 AB - TGF-beta exerts suppressive effects on immunity, but its potential applications in therapy of ocular autoimmunity have not been widely explored. In the present study, the effects of TGF-beta on uveitogenic T cells were examined. The effects of TGF-beta on newly primed cells from mice given a uveitogenic regimen of interphotoreceptor retinoid-binding protein (IRBP) were compared with the effects on fully polarized Th1 cells from a long-term uveitogenic T-cell line. The parameters measured were T-cell proliferation, IFN-gamma production, induction of IL-12R expression, triggering of pathogenicity, and expression of costimulatory molecules on antigen-presenting cells (APCs) during in vitro exposure to antigen. TGF-beta suppressed B7.1 expression on APCs in cultures of lymph node cells from immunized mice. It also suppressed T-cell proliferation, IFN-gamma production, IL-12 receptor accumulation, and the IL-12-promoted acquisition of uveitogenic function. In contrast, the polarized Th1 cells were either resistant to suppression or were enhanced by TGF-beta. The results suggest that TGF-beta suppresses acquisition of effector functions by autopathogenic T cells, in part by interfering with their response to IL-12 through downregulation of IL-12R expression and in part through inhibition of APC function. The data suggest that although TGF-beta may effectively inhibit activation and recruitment of new T cells into the effector pool, it may be less effective in suppressing the reactivation of already polarized memory T cells that are less dependent on IL-12 and costimulation. JF - Investigative ophthalmology & visual science AU - Xu, Hui AU - Silver, Phyllis B AU - Tarrant, Teresa K AU - Chan, Chi-Chao AU - Caspi, Rachel R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1857, USA. Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 4805 EP - 4812 VL - 44 IS - 11 SN - 0146-0404, 0146-0404 KW - Antigens, CD80 KW - 0 KW - Eye Proteins KW - RNA, Messenger KW - Receptors, Interleukin KW - Receptors, Interleukin-12 KW - Retinol-Binding Proteins KW - Transforming Growth Factor beta KW - interstitial retinol-binding protein KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Th1 Cells -- immunology KW - Animals KW - Receptors, Interleukin -- metabolism KW - Receptors, Interleukin -- genetics KW - Interferon-gamma -- biosynthesis KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Antigens, CD80 -- metabolism KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Immunologic Memory KW - Enzyme-Linked Immunosorbent Assay KW - Flow Cytometry KW - Antigen-Presenting Cells KW - Female KW - Male KW - Uveitis -- prevention & control KW - Autoimmune Diseases -- prevention & control KW - Transforming Growth Factor beta -- pharmacology KW - Retinitis -- immunology KW - Retinitis -- prevention & control KW - Uveitis -- immunology KW - Retinitis -- chemically induced KW - Lymphocyte Activation -- drug effects KW - Autoimmune Diseases -- chemically induced KW - Uveitis -- chemically induced KW - Autoimmune Diseases -- immunology KW - T-Lymphocytes, Regulatory -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71297422?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+ophthalmology+%26+visual+science&rft.atitle=Tgf-beta+inhibits+activation+and+uveitogenicity+of+primary+but+not+of+fully+polarized+retinal+antigen-specific+memory-effector+T+cells.&rft.au=Xu%2C+Hui%3BSilver%2C+Phyllis+B%3BTarrant%2C+Teresa+K%3BChan%2C+Chi-Chao%3BCaspi%2C+Rachel+R&rft.aulast=Xu&rft.aufirst=Hui&rft.date=2003-11-01&rft.volume=44&rft.issue=11&rft.spage=4805&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-20 N1 - Date created - 2003-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exploration of dimensions of psychopathology in neuroleptic-naïve patients with recent-onset schizophrenia/schizophreniform disorder. AN - 71297170; 14572620 AB - Previous studies have suggested that schizophrenic psychopathology segregates into three orthogonal dimensions, viz., psychosis, negative and disorganization. Most of these reports were based on studies on medicated patients with varying degrees of chronicity. The present study aimed at exploring the dimensionality of psychopathology rated on the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) in a sample of 43 neuroleptic-naïve patients with recent-onset schizophrenia/schizophreniform disorder. Principal Components Analysis (PCA) of SANS and SAPS global ratings, excluding inattention but including inappropriate affect as a separate global rating, revealed that the symptoms segregated into three dimensions, viz., negative (affective flattening, alogia, avolition anhedonia and inappropriate affect), psychosis (delusions and hallucinations) and disorganization (positive formal thought disorder and bizarre behavior). Cumulatively these three dimensions explained 74.07% of the variance. The results suggest that the three dimensions of schizophrenic psychopathology are valid even in neuroleptic-naïve, recent-onset patients with schizophrenia/schizophreniform disorder. PCA of the SANS and SAPS individual items revealed similar findings, but psychotic symptoms loaded under two components, thus yielding a four-factor solution; however, this observation needs to be confirmed in a larger sample of neuroleptic-naïve schizophrenic patients. JF - Psychiatry research AU - John, John P AU - Khanna, Sumant AU - Thennarasu, K AU - Reddy, Srinivasa AD - Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Dharmaram P.O., Bangalore 560 029, India. jpj@nimhans.kar.nic.in Y1 - 2003/11/01/ PY - 2003 DA - 2003 Nov 01 SP - 11 EP - 20 VL - 121 IS - 1 SN - 0165-1781, 0165-1781 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Hallucinations -- psychology KW - Affective Symptoms -- diagnosis KW - Hallucinations -- diagnosis KW - Thinking KW - Schizophrenia, Disorganized -- psychology KW - Delusions -- psychology KW - Antipsychotic Agents -- therapeutic use KW - Humans KW - Principal Component Analysis KW - Affective Symptoms -- psychology KW - Psychometrics -- statistics & numerical data KW - Schizophrenia, Disorganized -- diagnosis KW - Adult KW - Delusions -- diagnosis KW - Middle Aged KW - Adolescent KW - Antipsychotic Agents -- adverse effects KW - Male KW - Female KW - Psychiatric Status Rating Scales KW - Psychotic Disorders -- psychology KW - Schizophrenia -- diagnosis KW - Schizophrenic Psychology KW - Psychotic Disorders -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71297170?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Exploration+of+dimensions+of+psychopathology+in+neuroleptic-na%C3%AFve+patients+with+recent-onset+schizophrenia%2Fschizophreniform+disorder.&rft.au=John%2C+John+P%3BKhanna%2C+Sumant%3BThennarasu%2C+K%3BReddy%2C+Srinivasa&rft.aulast=John&rft.aufirst=John&rft.date=2003-11-01&rft.volume=121&rft.issue=1&rft.spage=11&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 - 2004-04-21 N1 - Date created - 2003-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcription factor Nrf2 activation by inorganic arsenic in cultured keratinocytes: involvement of hydrogen peroxide. AN - 71296291; 14567983 AB - Inorganic arsenic is a well-documented human carcinogen that targets the skin. The induction of oxidative stress, as shown with arsenic, may have a bearing on the carcinogenic mechanism of this metalloid. The transcription factor Nrf2 is a key player in the regulation of genes encoding for many antioxidative response enzymes. Thus, the effect of inorganic arsenic (as sodium arsenite) on Nrf2 expression and localization was studied in HaCaT cells, an immortalized human keratinocyte cell line. We found, for the first time, that arsenic enhanced cellular expression of Nrf2 at the transcriptional and protein levels and activated expression of Nrf2-related genes in these cells. In addition, arsenic exposure caused nuclear accumulation of Nrf2 in association with downstream activation of Nrf2-mediated oxidative response genes. Arsenic simultaneously increased the expression of Keap1, a regulator of Nrf2 activity. The coordinated induction of Keap1 expression and nuclear Nrf2 accumulation induced by arsenic suggests that Keap1 is important to arsenic-induced Nrf2 activation. Furthermore, when cells were pretreated with scavengers of hydrogen peroxide (H(2)O(2)) such as catalase-polyethylene glycol (PEG-CAT) or Tiron, arsenic-induced nuclear Nrf2 accumulation was suppressed, whereas CuDIPSH, a cell-permeable superoxide dismutase (SOD) mimic compound that produces H(2)O(2) from superoxide (*O(2)(-)), enhanced Nrf2 nuclear accumulation. These results indicate that H(2)O(2), rather than *O(2)(-), is the mediator of nuclear Nrf2 accumulation. Additional study showed that arsenic causes increased cellular H(2)O(2) production and that H(2)O(2) itself has the ability to increase Nrf2 expression at both the transcription and protein levels in HaCaT cells. Taken together, these data clearly show that arsenic increases Nrf2 expression and activity at multiple levels and that H(2)O(2) is one of the mediators of this process. JF - Experimental cell research AU - Pi, Jingbo AU - Qu, Wei AU - Reece, Jeffrey M AU - Kumagai, Yoshito AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, NCI at NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2003/11/01/ PY - 2003 DA - 2003 Nov 01 SP - 234 EP - 245 VL - 290 IS - 2 SN - 0014-4827, 0014-4827 KW - Arsenites KW - 0 KW - Carrier Proteins KW - DNA Primers KW - DNA-Binding Proteins KW - Free Radical Scavengers KW - NF-E2-Related Factor 2 KW - NFE2L2 protein, human KW - RNA, Messenger KW - Receptors, G-Protein-Coupled KW - Sodium Compounds KW - Trans-Activators KW - Superoxides KW - 11062-77-4 KW - sodium arsenite KW - 48OVY2OC72 KW - Hydrogen Peroxide KW - BBX060AN9V KW - NAD(P)H Dehydrogenase (Quinone) KW - EC 1.6.5.2 KW - NQO1 protein, human KW - Index Medicus KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- genetics KW - Humans KW - NAD(P)H Dehydrogenase (Quinone) -- metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - Leucine Zippers KW - Oxidation-Reduction KW - Superoxides -- metabolism KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Receptors, G-Protein-Coupled -- metabolism KW - Oxidative Stress KW - Gene Expression Regulation KW - Free Radical Scavengers -- pharmacology KW - DNA Primers -- chemistry KW - Trans-Activators -- metabolism KW - Sodium Compounds -- pharmacology KW - Arsenites -- pharmacology KW - Trans-Activators -- genetics KW - Keratinocytes -- drug effects KW - Hydrogen Peroxide -- metabolism KW - DNA-Binding Proteins -- genetics KW - Keratinocytes -- cytology KW - Keratinocytes -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71296291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell+research&rft.atitle=Transcription+factor+Nrf2+activation+by+inorganic+arsenic+in+cultured+keratinocytes%3A+involvement+of+hydrogen+peroxide.&rft.au=Pi%2C+Jingbo%3BQu%2C+Wei%3BReece%2C+Jeffrey+M%3BKumagai%2C+Yoshito%3BWaalkes%2C+Michael+P&rft.aulast=Pi&rft.aufirst=Jingbo&rft.date=2003-11-01&rft.volume=290&rft.issue=2&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-02 N1 - Date created - 2003-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Stress hormone responses to corticotropin-releasing hormone in substance abusers without severe comorbid psychiatric disease. AN - 71292055; 14573313 AB - Preclinical data indicate a crucial role of stress in the acute effects of drugs of abuse, maintenance of self-administration, and susceptibility to relapse. Stress system activation may serve as a marker for a neurochemical dysfunction with prognostic significance in patients with addiction. We tested pituitary adrenocorticotrophin (ACTH) and adrenal cortisol response to ovine corticotropin-releasing hormone (oCRH) to assess the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis in seven nonsubstance-abusing subjects, 31 polysubstance-abusing subjects without depressive symptoms, and seven subjects with substance abuse and depressive symptoms. No subject met diagnostic criteria for depression or other severe psychiatric disease. Compared with normal control subjects, substance abusers showed significantly lower ACTH and cortisol responses over the course of oCRH stimulation (p <.0001). Substance abusers with depressive symptoms showed similarly blunted responses. Polysubstance abusers with no past or current diagnosis of other Axis I disorders show blunted ACTH and cortisol responses to oCRH administration. The finding of an activated HPA axis in this population suggests an overlapping role of central CRH and HPA axis activation in affective disorders and substance abuse, which is likely to constitute an endocrine milieu necessary for the maintenance of addictive behavior. These data support the role of future therapeutic trials with nonpeptide CRH receptor 1 antagonists in these patients. JF - Biological psychiatry AU - Contoreggi, Carlo AU - Herning, Ronald I AU - Na, Paul AU - Gold, Philip W AU - Chrousos, George AU - Negro, Paulo J AU - Better, Warren AU - Cadet, Jean L AD - Brain Imaging, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 2003/11/01/ PY - 2003 DA - 2003 Nov 01 SP - 873 EP - 878 VL - 54 IS - 9 SN - 0006-3223, 0006-3223 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Humans KW - Adult KW - Case-Control Studies KW - Time Factors KW - Male KW - Female KW - Comorbidity KW - Substance-Related Disorders -- physiopathology KW - Depression -- physiopathology KW - Hypothalamo-Hypophyseal System -- physiopathology KW - Adrenocorticotropic Hormone -- drug effects KW - Pituitary-Adrenal System -- physiopathology KW - Corticotropin-Releasing Hormone -- administration & dosage KW - Hydrocortisone -- blood KW - Adrenocorticotropic Hormone -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71292055?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Stress+hormone+responses+to+corticotropin-releasing+hormone+in+substance+abusers+without+severe+comorbid+psychiatric+disease.&rft.au=Contoreggi%2C+Carlo%3BHerning%2C+Ronald+I%3BNa%2C+Paul%3BGold%2C+Philip+W%3BChrousos%2C+George%3BNegro%2C+Paulo+J%3BBetter%2C+Warren%3BCadet%2C+Jean+L&rft.aulast=Contoreggi&rft.aufirst=Carlo&rft.date=2003-11-01&rft.volume=54&rft.issue=9&rft.spage=873&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-21 N1 - Date created - 2003-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitrate in public water supplies and the risk of colon and rectum cancers. AN - 71284359; 14569178 AB - Nitrate is a widespread contaminant of drinking water, but its potential health effects are unclear. In the body, nitrate is reduced to nitrite, which can react with amines and amides by nitrosation to form N-nitroso compounds, known animal carcinogens. N-nitroso compound formation is inhibited by certain nutrients, such as vitamin C, and increased by meat intake. We investigated the association of nitrate in public water supplies with incident colon and rectum cancers in a case-control study conducted in Iowa from 1986 to 1989. Nitrate levels in Iowa towns were linked to the participants' water source histories. We focused our analyses on the period from 1960 onward, during which nitrate measurements were more frequent, and we restricted analyses to those persons with public water supplies that had nitrate data (actual or imputed) for greater than 70% of this time period (376 colon cancer cases, 338 rectum cancer cases, and 1244 controls). There were negligible overall associations of colon or rectum cancers with measures of nitrate in public water supplies, including average nitrate and the number of years with elevated average nitrate levels. For more than 10 years with average nitrate greater than 5 mg/L, the odds ratio (OR) for colon cancer was 1.2 (95% confidence interval [CI] = 0.9-1.6) and for rectum the OR was 1.1 (CI = 0.7-1.5). However, nitrate exposure (>10 years with average nitrate >5 mg/L) was associated with increased colon cancer risk among subgroups with low vitamin C intake (OR = 2.0; CI = 1.2-3.3) and high meat intake (OR = 2.2; CI = 1.4-3.6). These patterns were not observed for rectum cancer. Our analyses suggest that any increased risk of colon cancer associated with nitrate in public water supplies might occur only among susceptible subpopulations. JF - Epidemiology (Cambridge, Mass.) AU - De Roos, Anneclaire J AU - Ward, Mary H AU - Lynch, Charles F AU - Cantor, Kenneth P AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. aderoos@fhcrc.org Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 640 EP - 649 VL - 14 IS - 6 SN - 1044-3983, 1044-3983 KW - Nitrates KW - 0 KW - Index Medicus KW - Water Pollution KW - Aged, 80 and over KW - Risk Factors KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Male KW - Female KW - Rectal Neoplasms -- chemically induced KW - Colonic Neoplasms -- epidemiology KW - Water Supply -- analysis KW - Nitrates -- poisoning KW - Rectal Neoplasms -- epidemiology KW - Colonic Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71284359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Nitrate+in+public+water+supplies+and+the+risk+of+colon+and+rectum+cancers.&rft.au=De+Roos%2C+Anneclaire+J%3BWard%2C+Mary+H%3BLynch%2C+Charles+F%3BCantor%2C+Kenneth+P&rft.aulast=De+Roos&rft.aufirst=Anneclaire&rft.date=2003-11-01&rft.volume=14&rft.issue=6&rft.spage=640&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-04 N1 - Date created - 2003-10-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Epidemiology. 2004 May;15(3):378-80 [15097029] Epidemiology. 2003 Nov;14(6):635-6 [14569176] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparative geochemistry suggests Prototaxites was a gigantic fungus AN - 51782789; 2004-081711 AB - The enigmatic Devonian fossil Prototaxites produced large, tree-like trunks up to six meters tall that were composed exclusively of three distinct types of interwoven tubes 5 to 50 microns in diameter. Since its original description as a conifer, Prototaxites has been interpreted as an alga, a lichen, and as an extinct lineage not closely related to any extant group. Most recently it has been interpreted as a fungal fruiting body due to its hyphae-like tissue composition--despite the absence of spores or unambiguous anatomical details that would ally it to any specific fungal group. Carbon isotopic ratios have been measured for Prototaxites and co-occurring fossils from one Upper Devonian and four Lower Devonian localities. Unlike contemporaneous vascular plants, Prototaxites samples have an isotopic range, within and between localities, of up to 13 per mil. If original, such a large range would be difficult to reconcile with autotrophy and would seem to require heterotrophic metabolism on isotopically distinct substrates, consistent with a fungal interpretation. The observed isotopic range comprises discrete light and heavy populations. The light values are close to those of vascular plants from the same localities, while the heavy values may be attributable to algal source carbon, potentially an important part of early terrestrial ecosystems despite poor representation in the macrofossil record. Ongoing organic analyses should provide additional information concerning diagenesis, as well as independent tests of biological interpretations. JF - Abstracts with Programs - Geological Society of America AU - Boyce, Charles Kevin AU - Hotton, Carol AU - Fogel, Marilyn L AU - Cody, George D AU - Hazen, Robert M AU - Knoll, Andrew H AU - Anonymous Y1 - 2003/11// PY - 2003 DA - November 2003 SP - 587 PB - Geological Society of America (GSA), Boulder, CO VL - 35 IS - 6 SN - 0016-7592, 0016-7592 KW - terrestrial environment KW - isotopes KW - Paleozoic KW - isotope ratios KW - biochemistry KW - C-13/C-12 KW - stable isotopes KW - size KW - paleoecology KW - morphology KW - problematic fossils KW - Prototaxites KW - fungi KW - Devonian KW - carbon KW - classification KW - taxonomy KW - geochemistry KW - 02D:Isotope geochemistry KW - 09:Paleobotany UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/51782789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Abstracts+with+Programs+-+Geological+Society+of+America&rft.atitle=Comparative+geochemistry+suggests+Prototaxites+was+a+gigantic+fungus&rft.au=Boyce%2C+Charles+Kevin%3BHotton%2C+Carol%3BFogel%2C+Marilyn+L%3BCody%2C+George+D%3BHazen%2C+Robert+M%3BKnoll%2C+Andrew+H%3BAnonymous&rft.aulast=Boyce&rft.aufirst=Charles&rft.date=2003-11-01&rft.volume=35&rft.issue=6&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Abstracts+with+Programs+-+Geological+Society+of+America&rft.issn=00167592&rft_id=info:doi/ LA - English DB - GeoRef N1 - Conference title - Geological Society of America, 2003 annual meeting N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. Reference includes data supplied by the Geological Society of America, Boulder, CO, United States N1 - Date revised - 2004-01-01 N1 - PubXState - CO N1 - Last updated - 2012-06-07 N1 - CODEN - GAAPBC N1 - SubjectsTermNotLitGenreText - biochemistry; C-13/C-12; carbon; classification; Devonian; fungi; geochemistry; isotope ratios; isotopes; morphology; paleoecology; Paleozoic; problematic fossils; Prototaxites; size; stable isotopes; taxonomy; terrestrial environment ER - TY - JOUR T1 - Social functioning in first grade: associations with earlier home and child care predictors and with current classroom experiences AN - 37801928; 2763184 AB - Family and child care factors from birth to 54 months, achievement and social outcomes at entry to school, and qualities of first-grade classrooms were used to predict first-grade social functioning for 864 children from the NICHD Study of Early Child Care. Child gender, mothers' partner status, maternal education and depressive symptoms, sensitivity of mothering, and amount of time spent in nonmaternal child care were significant predictors. Home and child care variables predicted social functioning through associations with prior social functioning rather than directly. More teacher-led structured activities in first-grade classrooms predicted mother's reports of more internalizing behavior. Classrooms rated as more emotionally supportive predicted lower levels of mother-reported internalizing behavior and concurrently observed indicators of competence. Reprinted by permission of the University of Chicago Press. © All rights reserved JF - Child development Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 1639 EP - 1662 VL - 74 IS - 6 SN - 0009-3920, 0009-3920 KW - Sociology KW - Childhood KW - Mothers KW - Parent-child relations KW - Family KW - Children KW - Child development KW - Child care KW - Motherhood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/37801928?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aibss&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+development&rft.atitle=Social+functioning+in+first+grade%3A+associations+with+earlier+home+and+child+care+predictors+and+with+current+classroom+experiences&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2003-11-01&rft.volume=74&rft.issue=6&rft.spage=1639&rft.isbn=&rft.btitle=&rft.title=Child+development&rft.issn=00093920&rft_id=info:doi/ LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 4748; 2212; 2211 652 5676 646 6091 2212; 2192; 2197 2212 6075 3483; 9178 4777 6093 6823; 8317 9184; 8316 ER - TY - JOUR T1 - Linkage analysis of a composite factor for the multiple metabolic syndrome: The National Heart, Lung, and Blood Institute Family Heart Study AN - 216476268; 14578304 AB - Recent studies have demonstrated significant genetic and phenotypic correlation underlying the clustering of traits involved in the multiple metabolic syndrome (MMS). The aim of this study was to identify chromosomal regions contributing to MMS-related traits represented by composite factors derived from factor analysis. Data from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study were subjected to a maximum likelihood-based factor analysis. These analyses generated an MMS factor that was loaded by BMI, waist-to-hip ratio, subscapular skinfold, triglycerides, HDL, homeostasis model assessment index, plasminogen activator inhibitor-1 antigen, and serum uric acid. Genetic data were obtained for 2,467 subjects from 387 three-generation families (402 markers, the NHLBI Mammalian Genotyping Service) and 1,082 subjects from 256 sibships (243 markers, the Utah Molecular Genetics Laboratory). Multipoint variance components linkage analysis (GENEHUNTER version 2.1) of the MMS factor was conducted in the combined marker set sample. The greatest evidence for linkage was found on chromosome 2, with a peak LOD of 3.34 at 240 cM. Suggestive linkage was also observed for regions on chromosomes 7, 12, 14, and 15. In summary, a genomic region on chromosome 2 may contain a pleiotropic locus contributing to the clustering of MMS-related phenotypes. JF - Diabetes AU - Tang, Weihong AU - Miller, Michael B AU - Rich, Stephen S AU - North, Kari E AU - et al Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 2840 EP - 7 CY - New York PB - American Diabetes Association VL - 52 IS - 11 SN - 00121797 KW - Medical Sciences--Endocrinology KW - Blood Glucose KW - Blood Proteins KW - United States KW - Blood Glucose -- metabolism KW - Humans KW - Body Mass Index KW - Chromosomes, Human, Pair 2 -- genetics KW - Likelihood Functions KW - Blood Proteins -- analysis KW - Multivariate Analysis KW - Genotype KW - Risk Factors KW - National Institutes of Health (U.S.) KW - Middle Aged KW - Female KW - Male KW - Metabolic Syndrome X -- genetics KW - Chromosome Mapping UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/216476268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes&rft.atitle=Linkage+analysis+of+a+composite+factor+for+the+multiple+metabolic+syndrome%3A+The+National+Heart%2C+Lung%2C+and+Blood+Institute+Family+Heart+Study&rft.au=Tang%2C+Weihong%3BMiller%2C+Michael+B%3BRich%2C+Stephen+S%3BNorth%2C+Kari+E%3Bet+al&rft.aulast=Tang&rft.aufirst=Weihong&rft.date=2003-11-01&rft.volume=52&rft.issue=11&rft.spage=2840&rft.isbn=&rft.btitle=&rft.title=Diabetes&rft.issn=00121797&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Diabetes Association Nov 2003 N1 - Last updated - 2013-02-06 N1 - CODEN - DIAEAZ ER - TY - JOUR T1 - TRANSFUSION PRACTICE: Management of severe VWD with cryoprecipitate collected by repeated apheresis of a single dedicated donor AN - 20845628; 6597964 AB - BACKGROUND:Rare and severe forms of VWD are associated with trace or absent VWF. The feasibility of supporting a child with severe VWD from birth through age 12 with cryoprecipitate derived from DDAVP-stimulated plasma exchange of a single dedicated donor is reported. STUDY DESIGN AND METHODS:An infant with excessive hemorrhage at circumcision was found to have Type 3 VWD. His father carried an allele with a mutation at the level of VWF mRNA expression but did not have a history of bleeding. Cryoprecipitate was prepared from serial DDAVP-stimulated plasma exchanges of the father. RESULTS:Repeated plasma-exchange donations were performed to provide all of the VWF needed for his son. An average of 14 cryoprecipitate units was prepared from each donation, and the units contained markedly elevated levels of FVIII:C. The cryoprecipitate was stored for up to 102 months. Components tested after more than 8 years of storage showed 48 to 130 percent of original FVIII:C activity. Ninety-seven percent of the bleeding episodes, such as epistaxis, tongue-biting accidents, and other minor lacerations, were successfully managed with a single 50- to 100-percent replacement dose of FVIII. The patient experienced normal growth and development and is free of any long-term sequelae attributable to his disease. CONCLUSIONS:Cryoprecipitate prepared by repeated plasma exchange of a VWD carrier provided excellent hemostatic function, even after storage intervals of more than a year. Plasma exchange of a committed donor was a cost-effective and safe option for long-term management of VWD. JF - Transfusion AU - Pomper, Gregory J AU - Rick, Margaret E AU - Epstein, Jay S AU - Read, Elizabeth J AU - Leitman, Susan F AD - Departments of Transfusion Medicine and Laboratory Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health; and the Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, gpomper@wfubmc.edu Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 1514 EP - 1521 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 43 IS - 11 SN - 0041-1132, 0041-1132 KW - Health & Safety Science Abstracts KW - Storage KW - Feasibility studies KW - Historical account KW - Accidents KW - Age KW - Economics KW - transfusion KW - Mutation KW - Infants KW - H 0500:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20845628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transfusion&rft.atitle=TRANSFUSION+PRACTICE%3A+Management+of+severe+VWD+with+cryoprecipitate+collected+by+repeated+apheresis+of+a+single+dedicated+donor&rft.au=Pomper%2C+Gregory+J%3BRick%2C+Margaret+E%3BEpstein%2C+Jay+S%3BRead%2C+Elizabeth+J%3BLeitman%2C+Susan+F&rft.aulast=Pomper&rft.aufirst=Gregory&rft.date=2003-11-01&rft.volume=43&rft.issue=11&rft.spage=1514&rft.isbn=&rft.btitle=&rft.title=Transfusion&rft.issn=00411132&rft_id=info:doi/10.1046%2Fj.1537-2995.2003.00550.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-10-01 N1 - SuppNotes - Figures, 3; tables, 3; references, 19. N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Feasibility studies; Storage; Historical account; Age; Accidents; Economics; transfusion; Mutation; Infants DO - http://dx.doi.org/10.1046/j.1537-2995.2003.00550.x ER - TY - JOUR T1 - CYP17 polymorphisms in relation to risks of prostate cancer and benign prostatic hyperplasia: A population-based study in China AN - 20652452; 8079011 AB - Because androgens likely play a key role in prostate growth and prostate cancer development, variants of genes involved in androgen biosynthesis may be related to prostate cancer risk. The enzyme P450c17, encoded by the CYP17 gene, catalyzes the conversion of progesterone and pregnenolone into precursors of potent androgens. In the 5 promoter region of the CYP17 gene, a T (A1 allele) to C substitution (A2 allele) has been hypothesized to increase CYP17 gene expression, resulting in higher levels of androgens. To investigate a possible role of CYP17 in prostate diseases, we evaluated the risk of prostate cancer and benign prostatic hyperplasia (BPH) in relation to variation in CYP17 genotype in a population-based case-control study conducted in Shanghai, China. The study included 174 prostate cancer cases, 182 BPH cases and 274 population controls. We observed no statistically significant overall associations of CYP17 genotypes with prostate cancer risk, although associations of the A1/A1 (odds ratio (OR) =1.42, 95% confidence interval (CI) 0.83-2.48) and A1/A2 (OR 1.41, 95% CI 0.91-2.17) genotypes with prostate cancer were suggested. A similar association of the A1/A1 genotype with BPH was suggested. We found no associations of CYP17 genotypes with serum sex hormone levels or other biomarkers after correction for multiple comparisons. Large population-based studies are needed to clarify whether CYP17 plays a role in prostate cancer risk and whether genotype effects vary in different racial/ethnic and other subgroups. JF - International Journal of Cancer AU - Madigan, M Patricia AU - Gao, Yu-Tang AU - Deng, Jie AU - Pfeiffer, Ruth M AU - Chang, Bao-Li AU - Zheng, Siqun AU - Meyers, Deborah A AU - Stanczyk, Frank Z AU - Xu, Jianfeng AU - Hsing, Ann W AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA, hsinga@mail.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 271 EP - 275 PB - John Wiley & Sons, 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 107 IS - 2 SN - 0020-7136, 0020-7136 KW - Genetics Abstracts; Risk Abstracts KW - Progesterone KW - Gene polymorphism KW - Statistical analysis KW - Genotypes KW - Hormones KW - Sex hormones KW - Promoters KW - Pregnenolone KW - prostate cancer KW - population control KW - Benign KW - Bioindicators KW - Biosynthesis KW - Enzymes KW - Population studies KW - biomarkers KW - Hyperplasia KW - Steroid 17 alpha -monooxygenase KW - Prostate cancer KW - China, People's Rep. KW - China, People's Rep., Shanghai KW - Androgens KW - R2 23060:Medical and environmental health KW - G 07730:Development & Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20652452?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Cancer&rft.atitle=CYP17+polymorphisms+in+relation+to+risks+of+prostate+cancer+and+benign+prostatic+hyperplasia%3A+A+population-based+study+in+China&rft.au=Madigan%2C+M+Patricia%3BGao%2C+Yu-Tang%3BDeng%2C+Jie%3BPfeiffer%2C+Ruth+M%3BChang%2C+Bao-Li%3BZheng%2C+Siqun%3BMeyers%2C+Deborah+A%3BStanczyk%2C+Frank+Z%3BXu%2C+Jianfeng%3BHsing%2C+Ann+W&rft.aulast=Madigan&rft.aufirst=M&rft.date=2003-11-01&rft.volume=107&rft.issue=2&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.11378 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-04-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Progesterone; Gene polymorphism; Statistical analysis; Population studies; Enzymes; Genotypes; biomarkers; Sex hormones; Promoters; Hyperplasia; Prostate cancer; Steroid 17 alpha -monooxygenase; Pregnenolone; Androgens; Benign; Bioindicators; Biosynthesis; prostate cancer; Hormones; population control; China, People's Rep., Shanghai; China, People's Rep. DO - http://dx.doi.org/10.1002/ijc.11378 ER - TY - JOUR T1 - Functional neuroimaging: a new generation of human brain studies in obesity research AN - 20226837; 6627583 AB - Obesity is predominantly caused by overeating, an abnormal behaviour for which there is no unequivocal neurophysiological explanation. Functional neuroimaging techniques, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), have recently emerged as new tools to search for regions of the brain that are involved in the regulation of eating behaviours and those that are involved in the pathophysiology of obesity. Using these techniques, a limited number of studies have provided the first in vivo images of the human hypothalamic response to nutritional stimuli and revealed the complexity of the human brain response to hunger, taste, and satiation. Selective differences have been reported in the functional architecture of the brain of obese and lean individuals. We discuss current use and possible future developments of functional neuroimaging applied to obesity research. We conclude that functional neuroimaging provides an increasingly important tool for investigating how different regions of the brain work in concert to orchestrate normal eating behaviours and how they conspire to produce obesity and other eating disorders. JF - Obesity Reviews AU - Tataranni, P A AU - DelParigi, A AD - CDNS, NIDDK-NIH-DHHS, Phoenix, AZ, USA, antoniot@mail.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 229 EP - 238 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 4 IS - 4 SN - 1467-7881, 1467-7881 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Hunger KW - Brain mapping KW - Obesity KW - Hypothalamus KW - Neuroimaging KW - Satiety KW - Eating disorders KW - Functional magnetic resonance imaging KW - Functional anatomy KW - Taste KW - Reviews KW - Positron emission tomography KW - Brain architecture KW - W 30910:Imaging KW - N3 11001:Behavioral and Cognitive Neuroscience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20226837?accountid=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=Obesity+Reviews&rft.atitle=Functional+neuroimaging%3A+a+new+generation+of+human+brain+studies+in+obesity+research&rft.au=Tataranni%2C+P+A%3BDelParigi%2C+A&rft.aulast=Tataranni&rft.aufirst=P&rft.date=2003-11-01&rft.volume=4&rft.issue=4&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Obesity+Reviews&rft.issn=14677881&rft_id=info:doi/10.1046%2Fj.1467-789X.2003.00111.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - SuppNotes - Figures, 3; tables, 1; references, 74. N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Hunger; Obesity; Brain mapping; Neuroimaging; Hypothalamus; Satiety; Eating disorders; Functional magnetic resonance imaging; Functional anatomy; Taste; Reviews; Positron emission tomography; Brain architecture DO - http://dx.doi.org/10.1046/j.1467-789X.2003.00111.x ER - TY - JOUR T1 - Toxicogenomic approach for assessing toxicant-related disease AN - 19260589; 5848541 AB - The problems of identifying environmental factors involved in the etiology of human disease and performing safety and risk assessments of drugs and chemicals have long been formidable issues. Three principal components for predicting potential human health risks are: (1) the diverse structure and properties of thousands of chemicals and other stressors in the environment; (2) the time and dose parameters that define the relationship between exposure and disease; and (3) the genetic diversity of organisms used as surrogates to determine adverse chemical effects. The global techniques evolving from successful genomics efforts are providing new exciting tools with which to address these intractable problems of environmental health and toxicology. In order to exploit the scientific opportunities, the National Institute of Environmental Health Sciences has created the National Center for Toxicogenomics (NCT). The primary mission of the NCT is to use gene expression technology, proteomics and metabolite profiling to create a reference knowledge base that will allow scientists to understand mechanisms of toxicity and to be able to predict the potential toxicity of new chemical entities and drugs. A principal scientific objective underpinning the use of microarray analysis of chemical exposures is to demonstrate the utility of signature profiling of the action of drugs or chemicals and to utilize microarray methodologies to determine biomarkers of exposure and potential adverse effects. The initial approach of the NCT is to utilize proof-of-principle experiments in an effort to 'phenotypically anchor' the altered patterns of gene expression to conventional parameters of toxicity and to define dose and time relationships in which the expression of such signature genes may precede the development of overt toxicity. The microarray approach is used in conjunction with proteomic techniques to identify specific proteins that may serve as signature biomarkers. The longer-range goal of these efforts is to develop a reference relational database of chemical effects in biological systems (CEBS) that can be used to define common mechanisms of toxicity, chemical and drug actions, to define cellular pathways of response, injury and, ultimately, disease. In order to implement this strategy, the NCT has created a consortium of research organizations and private sector companies to actively collaborative in populating the database with high quality primary data. The evolution of discrete databases to a knowledge base of toxicogenomics will be accomplished through establishing relational interfaces with other sources of information on the structure and activity of chemicals such as that of the National Toxicology Program (NTP) and with databases annotating gene identity, sequence, and function. JF - Mutation Research-Reviews in Mutation Research AU - Waters, MD AU - Olden, K AU - Tennant, R W AD - National Center for Toxigenomics, National Institute of Environmental Health Sciences, P.O. Box 12233, MD F1-05, 111 Alexander Drive, Research Triangle Park, NC 27709-2233, USA, waters2@niehs.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 415 EP - 424 VL - 544 IS - 2-3 SN - 1383-5742, 1383-5742 KW - National Center for Toxicogenomics KW - Genetics Abstracts; Toxicology Abstracts KW - Chemicals KW - Databases KW - Reviews KW - Risk factors KW - Environmental factors KW - Drugs KW - Public health KW - X 24250:Reviews KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19260589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Reviews+in+Mutation+Research&rft.atitle=Toxicogenomic+approach+for+assessing+toxicant-related+disease&rft.au=Waters%2C+MD%3BOlden%2C+K%3BTennant%2C+R+W&rft.aulast=Waters&rft.aufirst=MD&rft.date=2003-11-01&rft.volume=544&rft.issue=2-3&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Reviews+in+Mutation+Research&rft.issn=13835742&rft_id=info:doi/10.1016%2Fj.mrrev.2003.06.014 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Chemicals; Databases; Risk factors; Reviews; Drugs; Environmental factors; Public health DO - http://dx.doi.org/10.1016/j.mrrev.2003.06.014 ER - TY - JOUR T1 - The impact of new technologies on human population studies AN - 19256282; 5848544 AB - Human population studies involve clinical or epidemiological observations that associate environmental exposures with health endpoints and disease. Clearly, these are the most sought after data to support assessments of human health risk from environmental exposures. However, the foundations of many health risk assessments rest on experimental studies in rodents performed at high doses that elicit adverse outcomes, such as organ toxicity or tumors. Using the results of human studies and animal data, risk assessors define the levels of environmental exposures that may lead to disease in a portion of the population. These decisions on potential health risks are frequently based on the use of default assumptions that reflect limitations in our scientific knowledge. An important immediate goal of toxicogenomics, including proteomics and metabonomics, is to offer the possibility of making decisions affecting public health and public based on detailed toxicity, mechanistic, and exposure data in which many of the uncertainties have been eliminated. Ultimately, these global technologies will dramatically impact the practice of public health and risk assessment as applied to environmental health protection. The impact is already being felt in the practice of toxicology where animal experimentation using highly controlled dose-time parameters is possible. It is also being seen in human population studies where understanding human genetic variation and genomic reactions to specific environmental exposures is enhancing our ability to uncover the causes of variations in human response to environmental exposures. These new disciplines hold the promise of reducing the costs and time lines associated with animal and human studies designed to assess both the toxicity of environmental pollutants and efficacy of therapeutic drugs. However, as with any new science, experience must be gained before the promise can be fulfilled. Given the numbers and diversity of drugs, chemicals and environmental agents; the various species in which they are studied and the time and dose factors that are critical to the induction of beneficial and adverse effects, it is only through the development of a profound knowledge base that toxicology and environmental health can rapidly advance. The National Institute of Environmental Health Sciences (NIEHS), National Center for Toxicogenomics and its university-based Toxicogenomics Research Consortium (TRC), and resource contracts, are engaged in the development, application and standardization of the science upon which to the build such a knowledge base on Chemical Effects in Biological Systems (CEBS). In addition, the NIEHS Environmental Genome Project (EGP) is working to systematically identify and characterize common sequence polymorphisms in many genes with suspected roles in determining chemical sensitivity. The rationale of the EGP is that certain genes have a greater than average influence over human susceptibility to environmental agents. If we identify and characterize the polymorphism in those genes, we will increase our understanding of human disease susceptibility. This knowledge can be used to protect susceptible individuals from disease and to reduce adverse exposure and environmentally induced disease. JF - Mutation Research-Reviews in Mutation Research AU - Waters, MD AU - Selkirk, J K AU - Olden, K AD - National Center for Toxicogenomics, 111 Alexander Drive, P.O. Box 12233, MD F1-05, Research Triangle Park, NC 27709-2233, USA, waters2@niehs.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 349 EP - 360 VL - 544 IS - 2-3 SN - 1383-5742, 1383-5742 KW - Chemical Effects in Biological Systems KW - NIEHS Environmental Genome Project KW - man KW - Genetics Abstracts; Toxicology Abstracts KW - Population studies KW - Toxicity KW - Environmental factors KW - Public health KW - Reviews KW - Diseases KW - Drugs KW - Toxicity testing KW - Pollution KW - X 24250:Reviews KW - G 07439:General - reviews/ethics, etc. UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19256282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Reviews+in+Mutation+Research&rft.atitle=The+impact+of+new+technologies+on+human+population+studies&rft.au=Waters%2C+MD%3BSelkirk%2C+J+K%3BOlden%2C+K&rft.aulast=Waters&rft.aufirst=MD&rft.date=2003-11-01&rft.volume=544&rft.issue=2-3&rft.spage=349&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Reviews+in+Mutation+Research&rft.issn=13835742&rft_id=info:doi/10.1016%2Fj.mrrev.2003.06.022 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Population studies; Environmental factors; Public health; Toxicity; Toxicity testing; Pollution; Drugs; Diseases DO - http://dx.doi.org/10.1016/j.mrrev.2003.06.022 ER - TY - JOUR T1 - Environmental hazards to children's health in the modern world AN - 19255754; 5848529 AB - Patterns of illness in children have changed dramatically in the last century, and will continue to change in this century. The major diseases confronting children are now chronic and disabling conditions termed the 'new pediatric morbidity'-asthma, leukemia and brain cancer, neurodevelopmental dysfunction and neurobehavioral abnormality, reproductive and systemic developmental problems. Chemical toxicants in the environment, poverty, and little or no access to health care are all factors contributing to life-threatening pediatric diseases; children are uniquely vulnerable to chemical toxicants because of their disproportionately heavy exposures and their inherent biological growth and development. Genetic susceptibility and environmental exposures during vulnerable periods of development are also important contributors to the etiologies of many diseases of childhood. It is vital that we develop a better understanding of the mechanisms and interactions between nutrition, infectious disease, environmental exposures, and genetic predisposition in order to develop better prevention methods. This paper briefly examines modern contributors to children's environmental health problems, efforts to date on both the regional and international level to address these challenges, and reflects upon major research needs that must be addressed in order to close the gaps that exist in our understanding of the relationship between environmental exposures and children's health. JF - Mutation Research-Reviews in Mutation Research AU - Suk, WA AU - Murray, K AU - Avakian, MD AD - Center for Risk and Integrated Sciences, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 235 EP - 242 VL - 544 IS - 2-3 SN - 1383-5742, 1383-5742 KW - man KW - Genetics Abstracts; Toxicology Abstracts KW - Children KW - Environmental factors KW - Nutrition KW - Public health KW - Risk factors KW - Reviews KW - Diseases KW - X 24250:Reviews KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19255754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Reviews+in+Mutation+Research&rft.atitle=Environmental+hazards+to+children%27s+health+in+the+modern+world&rft.au=Suk%2C+WA%3BMurray%2C+K%3BAvakian%2C+MD&rft.aulast=Suk&rft.aufirst=WA&rft.date=2003-11-01&rft.volume=544&rft.issue=2-3&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Reviews+in+Mutation+Research&rft.issn=13835742&rft_id=info:doi/10.1016%2Fj.mrrev.2003.06.007 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Public health; Children; Nutrition; Diseases; Environmental factors; Risk factors DO - http://dx.doi.org/10.1016/j.mrrev.2003.06.007 ER - TY - JOUR T1 - Community outreach as an iterative dialogue among scientists and communities in the Texas gulf coast region AN - 19255235; 5848547 AB - In response to significant environmental health challenges in Southeast Texas, a National Institute for Environmental Health Sciences Center at the University of Texas Medical Branch at Galveston was created to promote and conduct inter-disciplinary research in the areas of: (1) the molecular biology of DNA repair, replication and mutagenesis, (2) asthma pathogenesis in response to oxidative stress and viral exposures, and (3) environmental toxicant biotransformation. In addition, the NIEHS Center maintains close ties with neighboring communities through an active Community Outreach Education Program (COEP) that develops and disseminates translational materials for use in environmental health awareness outreach, toxicology consultation, K-12 curriculum enrichment and in developing site-specific Community Partnership projects. The COEP core service divisions include: Environmental Arts Sciences, Asthma Outreach Education, Theater Outreach Education, and Public Forum Toxics Assistance. Public Forums focus on the use of Augusto Boal's Forum Theater dramaturgy to include the voices and local knowledge of communities within the process of Participatory Research. Forums create the preconditions for significant partnerships that link the hazardous risk perceptions and environmental health needs of communities with the expertise of NIEHS Center investigators and translational services provided through COEP outreach programs. The Forum process also creates leadership cores within environmentally challenged communities that facilitate the ongoing translational process and maintain the vital linkage between the health needs of communities and the analytic tools and the field and clinical technologies of the environmental sciences. JF - Mutation Research-Reviews in Mutation Research AU - Sullivan, J AU - Diamond, P D AU - Kaplan, CL AU - Mader, T J AU - Santa, R AU - Lloyd, R S AD - Community Outreach Education Program, Sealy Center for Environmental Health and Medicine/National Institute of Environmental Health Sciences Center, University of Texas Medical Branch, Galveston, TX 77555-1071, USA, josulliv@utmb.edu Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 331 EP - 338 PB - Elsevier B.V. VL - 544 IS - 2-3 SN - 1383-5742, 1383-5742 KW - National Institute for Environmental Health Sciences Center KW - Genetics Abstracts; Toxicology Abstracts KW - DNA biosynthesis KW - Communities KW - Oxidative stress KW - Risk factors KW - Viruses KW - Asthma KW - USA, Texas KW - DNA repair KW - Environmental factors KW - Public health KW - Mutagenesis KW - X 24250:Reviews KW - G 07439:General - reviews/ethics, etc. UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19255235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Reviews+in+Mutation+Research&rft.atitle=Community+outreach+as+an+iterative+dialogue+among+scientists+and+communities+in+the+Texas+gulf+coast+region&rft.au=Sullivan%2C+J%3BDiamond%2C+P+D%3BKaplan%2C+CL%3BMader%2C+T+J%3BSanta%2C+R%3BLloyd%2C+R+S&rft.aulast=Sullivan&rft.aufirst=J&rft.date=2003-11-01&rft.volume=544&rft.issue=2-3&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Reviews+in+Mutation+Research&rft.issn=13835742&rft_id=info:doi/10.1016%2Fj.mrrev.2003.06.015 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - DNA biosynthesis; Communities; Oxidative stress; Risk factors; Viruses; Asthma; DNA repair; Environmental factors; Mutagenesis; Public health; USA, Texas DO - http://dx.doi.org/10.1016/j.mrrev.2003.06.015 ER - TY - JOUR T1 - Neurobehavioral Performance and Work Experience in Florida Farmworkers AN - 19247708; 5814982 AB - Farmworkers experience many work-related hazards, including exposure to neurotoxicants. We compared neurobehavioral performance of 288 farmworkers in central Florida who had done farm work for at least 1 month with 51 controls who had not. Most of the farmworkers had worked in one or more of three types of agriculture: ornamental ferns, nurseries, or citrus fruit. We collected information on farm work history in a structured interview and evaluated neurobehavioral performance using a battery of eight tests. Analyses were adjusted for established confounders including age, sex, education, and acculturation. Ever having done farm work was associated with poor performance on four tests--digit span [odds ratio (OR) = 1.90; 95% confidence interval (CI), 1.02-3.53], tapping (coefficient = 4.13; 95% CI, 0.00-8.27), Santa Ana test (coefficient = 1.34; 95% CI, 0.29-2.39), and postural sway (coefficient = 4.74; 95% CI, -2.20 to 11.7)--but had little effect on four others: symbol digit latency, vibrotactile threshold, visual contrast sensitivity, and grip strength. Associations with farm work were similar in magnitude to associations with personal characteristics such as age and sex. Longer duration of farm work was associated with worse performance. Associations with fern work were more consistent than associations with nursery or citrus work. Deficits related to the duration of work experience were seen in former as well as current farmworkers, and decreased performance was related to chronic exposure even in the absence of a history of pesticide poisoning. We conclude that long-term experience of farm work is associated with measurable deficits in cognitive and psychomotor function. JF - Environmental Health Perspectives AU - Kamel, F AU - Rowland, A S AU - Park, L P AU - Anger, W K AU - Baird, D D AU - Gladen, B C AU - Moreno, T AU - Stallone, L AU - Sandler, D P AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Box 12233, MD A3-05, Research Triangle Park, NC 27709 USA, kamel@niehs.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 1765 EP - 1772 VL - 111 IS - 14 SN - 0091-6765, 0091-6765 KW - cognitive ability KW - farming KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Agriculture KW - Farms KW - USA, Florida KW - Behavior KW - Toxicants KW - Neurotoxicity KW - Pesticides KW - Occupational exposure KW - X 24132:Chronic exposure KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19247708?accountid=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=Neurobehavioral+Performance+and+Work+Experience+in+Florida+Farmworkers&rft.au=Kamel%2C+F%3BRowland%2C+A+S%3BPark%2C+L+P%3BAnger%2C+W+K%3BBaird%2C+D+D%3BGladen%2C+B+C%3BMoreno%2C+T%3BStallone%2C+L%3BSandler%2C+D+P&rft.aulast=Kamel&rft.aufirst=F&rft.date=2003-11-01&rft.volume=111&rft.issue=14&rft.spage=1765&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Fehp.6341 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Farms; Toxicants; Behavior; Pesticides; Neurotoxicity; Occupational exposure; Agriculture; USA, Florida DO - http://dx.doi.org/10.1289/ehp.6341 ER - TY - JOUR T1 - Risk of melanoma in relation to smoking, alcohol intake, and other factors in a large occupational cohort AN - 19241141; 5811843 AB - Objective: To investigate whether smoking, alcohol intake, female hormonal or anthropometric factors affect melanoma risk. Methods: Using Cox proportional hazards regression analyses, we analyzed 68,588 white subjects (79% female) from the US Radiologic Technologists (USRT) Study who were cancer-free (other than non-melanoma skin cancer) as of the first of two self-administered questionnaires. Follow-up covered 698, 028 person-years, with 207 cases of melanoma. Results: We found that melanoma risk was not associated with height, weight or BMI, nor with age at menarche, menopausal status, use of hormone replacement therapy, parity, age at first birth or oral contraceptive use. Melanoma risk was elevated with increasing alcohol use (RR: 2.1; 95% CI: 0.9-4.8, for >14 drinks/week compared to never drinking; (p(trend) = 0.08)). Smoking for long durations compared to never smoking was inversely related to melanoma risk (RR: 0.6; 0.3-1.3; greater than or equal to 30 years; p(trend) = 0.03), though risk was not associated with number of packs smoked per day. Conclusions: None of the anthropometric or female reproductive/hormonal factors evaluated were related to melanoma risk. It is unclear whether the positive association with alcohol intake and inverse association with smoking for long duration are causal. The alcohol and smoking findings warrant detailed assessment in studies with substantial statistical power where potential biases can be more fully evaluated. JF - Cancer Causes & Control AU - Freedman, D M AU - Sigurdson, A AU - Doody, M M AU - Rao, R S AU - Linet AD - National Cancer Institute, Division of Cancer Epidemiology and Genetics, Radiation Epidemiology Branch, Executive Plaza South, Room 7036 6120 Executive Plaza Boulevard Bethesda, MD 20892, USA, mf101e@nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 847 EP - 857 VL - 14 IS - 9 SN - 0957-5243, 0957-5243 KW - man KW - Toxicology Abstracts KW - Smoking KW - Cigarettes KW - Tobacco KW - Melanoma KW - Ethanol KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19241141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Risk+of+melanoma+in+relation+to+smoking%2C+alcohol+intake%2C+and+other+factors+in+a+large+occupational+cohort&rft.au=Freedman%2C+D+M%3BSigurdson%2C+A%3BDoody%2C+M+M%3BRao%2C+R+S%3BLinet&rft.aulast=Freedman&rft.aufirst=D&rft.date=2003-11-01&rft.volume=14&rft.issue=9&rft.spage=847&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Ethanol; Melanoma; Smoking; Cigarettes; Tobacco ER - TY - JOUR T1 - Segregation of the Escherichia coli chromosome terminus AN - 19230798; 5772743 AB - We studied the segregation of the replication terminus of the Escherichia coli chromosome by time-lapse and still photomicroscopy. The replicated termini lie together at the cell centre. They rapidly segregate away from each other immediately before cell division. At fast growth rate, the copies move progressively and quickly toward the centres of the new-born cells. At slow growth rate, the termini usually remain near the inner cell pole and migrate to the cell centre in the middle of the cell cycle. A terminus domain of about 160kb, roughly centred on the dif recombination site, segregated as a unit at cell division. Sequences outside this domain segregated before division, giving two separate foci in predivision cells. Resolution of chromosome dimers via the terminus dif site requires the XerC recombinase and an activity of the FtsK protein that is thought to align the dif sequences at the cell centre. We found that anchoring of the termini at the cell centre and proper segregation at cell division occurred normally in the absence of recombination via the XerC recombinase. Anchoring and proper segregation were, however, frequently disrupted when the C-terminal domain of FtsK was truncated. JF - Molecular Microbiology AU - Li, Y AU - Youngren, B AU - Sergueev, K AU - Austin, S AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute, CCR, NCI-Frederick, Frederick, Maryland 21702-1201, USA., austin@ncifcrf.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 825 EP - 834 PB - Blackwell Science Ltd VL - 50 IS - 3 SN - 0950-382X, 0950-382X KW - FtsK protein KW - XerC protein KW - recombinase KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Recombination KW - Chromosomes KW - Cell division KW - Segregation KW - Escherichia coli KW - N 14920:Chromatin & chromosomes KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19230798?accountid=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=Segregation+of+the+Escherichia+coli+chromosome+terminus&rft.au=Li%2C+Y%3BYoungren%2C+B%3BSergueev%2C+K%3BAustin%2C+S&rft.aulast=Li&rft.aufirst=Y&rft.date=2003-11-01&rft.volume=50&rft.issue=3&rft.spage=825&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2003.03746.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Segregation; Cell division; Recombination; Chromosomes DO - http://dx.doi.org/10.1046/j.1365-2958.2003.03746.x ER - TY - JOUR T1 - Signal pathway profiling of ovarian cancer from human tissue specimens using reverse-phase protein microarrays AN - 19230656; 5806720 AB - Defects in cell signaling pathways play a central role in cancer cell growth, survival, invasion and metastasis. An important goal of proteomics is to characterize and develop "circuit maps" of these signaling pathways in normal and diseased cells. We have used reverse-phase protein array technology coupled with laser capture microdissection and phospho-specific antibodies to examine the activation status of several key molecular "gates" involved in cell survival and proliferation signaling in human ovarian tumor tissue. The levels of activated extracellular-regulated kinase (ERK1/2) varied considerably in tumors of the same histotype, but no significant differences between histotypes were observed. Advanced stage tumors had slightly higher levels of phosphorylated ERK1/2 compared to early stage tumors. The activation status of Akt and glycogen synthase kinase 3 beta , key proteins and indicators of the state of the phosphatidylinositol 3-kinase/Akt pro-survival pathway also showed more variation within each histotype than between the histoypes studied. Our results demonstrate the utility of reverse phase protein microarrays for the multiplexed analysis of signal transduction from discreet cell populations of cells procured directly from human ovarian tumor specimens and suggest that patterns in signal pathway activation in ovarian tumors may be patient-specific rather than type or stage specific. JF - Proteomics AU - Wulfkuhle, J D AU - Aquino, JA AU - Calvert, V S AU - Fishman, DA AU - Coukos, G AU - Liotta, LA AU - Petricoin, EF III AD - Center for Cancer Research, National Cancer Institute, Building 29A/Room 2B20, 8800 Rockville Pike, Bethesda, MD 20892, USA, wulfkuhle@cber.fda.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 2085 EP - 2090 VL - 3 IS - 11 SN - 1615-9853, 1615-9853 KW - protein microarrays KW - proteomics KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Metastases KW - Ovarian cancer KW - Antibodies KW - 1-Phosphatidylinositol 3-kinase KW - Protein kinase KW - Tumors KW - Specimens KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19230656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteomics&rft.atitle=Signal+pathway+profiling+of+ovarian+cancer+from+human+tissue+specimens+using+reverse-phase+protein+microarrays&rft.au=Wulfkuhle%2C+J+D%3BAquino%2C+JA%3BCalvert%2C+V+S%3BFishman%2C+DA%3BCoukos%2C+G%3BLiotta%2C+LA%3BPetricoin%2C+EF+III&rft.aulast=Wulfkuhle&rft.aufirst=J&rft.date=2003-11-01&rft.volume=3&rft.issue=11&rft.spage=2085&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&rft_id=info:doi/10.1002%2Fpmic.200300591 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Protein Microarrays. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Ovarian cancer; Specimens; 1-Phosphatidylinositol 3-kinase; Metastases; Antibodies; Protein kinase; Tumors DO - http://dx.doi.org/10.1002/pmic.200300591 ER - TY - JOUR T1 - Protein microarrays: Molecular profiling technologies for clinical specimens AN - 19221158; 5806721 AB - Proteomics, the study of protein function within biologic systems, will further our understanding of cancer pathogenesis. Coupled with transcript profiling, proteomics can herald the advent of molecular therapy tailored to the individual patient's neoplasm. Protein microarrays, one emerging class of proteomic technologies, have broad applications for discovery and quantitative analysis. This technology is uniquely suited to gather information about the post-translational modifications of proteins reflecting the activity state of signal pathways and networks. Protein microarrays now make it feasible to conduct signal network profiling within cellular samples. Nevertheless, to be successful, design and use of protein microarrays must take into consideration enormous analytical challenges. A subclass of protein microarrays, Reverse Phase Arrays, created to meet these challenges, has been optimized for use with tissue specimens, and is now in use for the analysis of biopsy samples for clinical trial research. JF - Proteomics AU - Espina, V AU - Mehta, AI AU - Winters, ME AU - Calvert, V AU - Wulfkuhle, J AU - Petricoin, EF III AU - Liotta, LA AD - National Cancer Institute, Building 10 Room B1B53, 9000 Rockville Pike, Bethesda, MD 20892, USA, espinav@mail.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 2091 EP - 2100 VL - 3 IS - 11 SN - 1615-9853, 1615-9853 KW - man KW - protein microarrays KW - proteomics KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Proteins KW - Biopsy KW - Clinical trials KW - Cancer KW - Specimens KW - Neoplasia KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19221158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteomics&rft.atitle=Protein+microarrays%3A+Molecular+profiling+technologies+for+clinical+specimens&rft.au=Espina%2C+V%3BMehta%2C+AI%3BWinters%2C+ME%3BCalvert%2C+V%3BWulfkuhle%2C+J%3BPetricoin%2C+EF+III%3BLiotta%2C+LA&rft.aulast=Espina&rft.aufirst=V&rft.date=2003-11-01&rft.volume=3&rft.issue=11&rft.spage=2091&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&rft_id=info:doi/10.1002%2Fpmic.200300592 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Protein Microarrays. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neoplasia; Specimens; Cancer; Clinical trials; Biopsy; Proteins DO - http://dx.doi.org/10.1002/pmic.200300592 ER - TY - JOUR T1 - Global analysis of small RNA and mRNA targets of Hfq AN - 19211146; 5772762 AB - Hfq, a bacterial member of the Sm family of RNA-binding proteins, is required for the action of many small regulatory RNAs that act by basepairing with target mRNAs. Hfq binds this family of small RNAs efficiently. We have used co-immunoprecipitation with Hfq and direct detection of the bound RNAs on genomic microarrays to identify members of this small RNA family. This approach was extremely sensitive; even Hfq-binding small RNAs expressed at low levels were readily detected. At least 15 of 46 known small RNAs in E. coli interact with Hfq. In addition, high signals in other intergenic regions suggested up to 20 previously unidentified small RNAs bind Hfq; five were confirmed by Northern analysis. Strong signals within genes and operons also were detected, some of which correspond to known Hfq targets. Within the argX-hisR-leuT-proM operon, Hfq appears to compete with RNase E and modulate RNA processing and degradation. Thus Hfq immunoprecipitation followed by microarray analysis is a highly effective method for detecting a major class of small RNAs as well as identifying new Hfq functions. JF - Molecular Microbiology AU - Zhang, A AU - Wassarman, K M AU - Rosenow, C AU - Tjaden, B C AU - Storz, G AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA., storz@helix.nih.gov storz@helix.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 1111 EP - 1124 PB - Blackwell Science Ltd VL - 50 IS - 4 SN - 0950-382X, 0950-382X KW - Hfq protein KW - ribonuclease E KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - RNA-binding protein KW - Escherichia coli KW - Chaperones KW - Operons KW - J 02726:RNA and ribosomes KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19211146?accountid=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=Global+analysis+of+small+RNA+and+mRNA+targets+of+Hfq&rft.au=Zhang%2C+A%3BWassarman%2C+K+M%3BRosenow%2C+C%3BTjaden%2C+B+C%3BStorz%2C+G%3BGottesman%2C+S&rft.aulast=Zhang&rft.aufirst=A&rft.date=2003-11-01&rft.volume=50&rft.issue=4&rft.spage=1111&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2003.03734.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Chaperones; RNA-binding protein; Operons DO - http://dx.doi.org/10.1046/j.1365-2958.2003.03734.x ER - TY - JOUR T1 - Internalization of OspA in rsCD14 complex and aggregated forms AN - 19211049; 5772744 AB - Although the spirochetal protein OspA is capable of stimulating immune cells in a CD14- and TLR2-dependent manner, little is known about how TLR2 receptor complex ligands, such as OspA, are handled by the cell once delivered. We examine here the internalization of the fluorescently derivatized forms of both the full length OspA lipoprotein delivered as a recombinant soluble CD14 (rsCD14) complex and the corresponding lipohexapeptide given to the cells as an aggregate. Both forms of OspA are internalized in a similar manner to acetylated low density lipoprotein (AcLDL), a scavenger receptor ligand. Acetylated low density lipoprotein is capable of competing for internalization with OspA even when OspA is delivered as a rsCD14 complex. We observe co-localization of OspA with lysosomes but not with the Golgi complex. These phenomena are similar between RAW264.7 macrophages and endothelial cells but change drastically when the cells are deprived of serum. Upon serum starvation, OspA shows some localization to the Golgi apparatus whereas the lipohexapeptide remains on the cell surface. Inhibition of internalization of OspA via treatment with cytochalasin D or of the lipohexapeptide via serum starvation does not interfere with TNF induction activity, consistent with signalling from the cell surface. JF - Molecular Microbiology AU - Welty, D M AU - Snyder, D S AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St. Hamilton, MT 59840, USA., ssnyder@bcm.tmc.edu Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 835 EP - 843 PB - Blackwell Science Ltd VL - 50 IS - 3 SN - 0950-382X, 0950-382X KW - OspA protein KW - Microbiology Abstracts B: Bacteriology KW - Endothelial cells KW - Macrophages KW - Starvation KW - Recombinants KW - Golgi apparatus KW - Fluorescence KW - Internalization KW - Lipoproteins KW - Ligands KW - Lipoproteins (low density) KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19211049?accountid=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=Internalization+of+OspA+in+rsCD14+complex+and+aggregated+forms&rft.au=Welty%2C+D+M%3BSnyder%2C+D+S&rft.aulast=Welty&rft.aufirst=D&rft.date=2003-11-01&rft.volume=50&rft.issue=3&rft.spage=835&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2003.03769.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lipoproteins; Recombinants; Fluorescence; Internalization; Ligands; Starvation; Golgi apparatus; Lipoproteins (low density); Macrophages; Endothelial cells DO - http://dx.doi.org/10.1046/j.1365-2958.2003.03769.x ER - TY - JOUR T1 - Comparative genomics, minimal gene-sets and the last universal common ancestor AN - 19182453; 5767412 AB - Comparative genomics, using computational and experimental methods, enables the identification of a minimal set of genes that is necessary and sufficient for sustaining a functional cell. For most essential cellular functions, two or more unrelated or distantly related proteins have evolved; only about 60 proteins, primarily those involved in translation, are common to all cellular life. The reconstruction of ancestral life-forms is based on the principle of evolutionary parsimony, but the size and composition of the reconstructed ancestral gene-repertoires depend on relative rates of gene loss and horizontal gene-transfer. The present estimate suggests a simple last universal common ancestor with only 500-600 genes. JF - Nature Reviews: Microbiology AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, NIH Building 38A, 8600 Rockville Pike, Bethesda, MD 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 127 EP - 136 PB - Nature Publishing Co., 345 Park Ave. S. 10th Floor New York NY 10010-1707 USA, [mailto:nature@natureny.com], [URL:http://www.nature.com/nature/] VL - 1 IS - 2 KW - Microbiology Abstracts B: Bacteriology KW - Gene transfer KW - Genetic analysis KW - Proteins KW - Viability KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19182453?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Reviews%3A+Microbiology&rft.atitle=Comparative+genomics%2C+minimal+gene-sets+and+the+last+universal+common+ancestor&rft.au=Koonin%2C+E+V&rft.aulast=Koonin&rft.aufirst=E&rft.date=2003-11-01&rft.volume=1&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Nature+Reviews%3A+Microbiology&rft.issn=&rft_id=info:doi/10.1038%2Fnrmicro751 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Genetic analysis; Proteins; Viability; Gene transfer DO - http://dx.doi.org/10.1038/nrmicro751 ER - TY - JOUR T1 - Temperature Sensing by the dsrA Promoter AN - 18888393; 5746400 AB - Synthesis of the small regulatory RNA DsrA is under temperature control. The minimal dsrA promoter of 36 bp contains sufficient information to ensure such regulation. In vivo, we have analyzed the critical elements responsible for the temperature control of dsrA by using a collection of chimeric promoters combining various elements of the dsrA promoter and the lacUV5 promoter, which does not respond to temperature. Our results favor an RNA polymerase-DNA interaction model instead of a trans-acting factor for temperature regulation. While all of the elements of the dsrA promoter contribute to temperature-sensitive expression, the sequence of the -10 box and the spacer region are the essential elements for the thermal response of the dsrA promoter. The proper context for these promoter elements, including at least one of the flanking elements, the -35 region or the start site region, is also required. Point mutations demonstrate that the sequence of the -10 box imposes constraints on the length and the sequence of the spacer and/or its AT richness, even at low temperature. These results show a complex interdependence of different regions in the promoter for temperature regulation. JF - Journal of Bacteriology AU - Repoila, F AU - Gottesman, S AD - Bldg. 37, Rm. 5132, NIH, Bethesda, MD 20892-4264, susang@helix.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 6609 EP - 6614 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 185 IS - 22 SN - 0021-9193, 0021-9193 KW - DsrA protein KW - dsrA gene KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - N 14662:Gene regulation KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18888393?accountid=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=Temperature+Sensing+by+the+dsrA+Promoter&rft.au=Repoila%2C+F%3BGottesman%2C+S&rft.aulast=Repoila&rft.aufirst=F&rft.date=2003-11-01&rft.volume=185&rft.issue=22&rft.spage=6609&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.185.22.6609-6614.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.185.22.6609-6614.2003 ER - TY - JOUR T1 - Synthesis and Deformylation of Staphylococcus aureus delta -Toxin Are Linked to Tricarboxylic Acid Cycle Activity AN - 18888356; 5746403 AB - In bacteria, translation initiates with formyl-methionine; however, the N- terminal formyl group is usually removed by peptide deformylase, an enzymatic activity requiring iron. Staphylococcus aureus delta -toxin is a 26-amino- acid polypeptide secreted predominantly with a formylated N-terminal methionine, which led us to investigate regulation of delta -toxin deformylation. We observed that during exponential and early postexponential growth, delta - toxin accumulated in the culture medium in formylated and deformylated forms. In contrast, only formylated delta -toxin accumulated after the early postexponential phase. The transition from producing both species of delta - toxin to producing only formyl-methionine-containing delta -toxin coincided with increased tricarboxylic acid (TCA) cycle activity. The TCA cycle contains several iron-requiring enzymes, which led us to hypothesize that TCA cycle induction depletes the iron in the culture medium, thereby inhibiting peptide deformylase activity. As expected, S. aureus depletes the iron in the culture medium between the postexponential and stationary phases of growth. Inhibition of delta -toxin deformylation was relieved by TCA cycle inactivation or by addition of supplemental iron to the culture medium. Of interest, peptides containing formyl-methionine are potent chemoattractants for neutrophils, suggesting that delta -toxin deformylation may have functional consequences. We found neutrophil chemotactic activity only with formylated delta -toxin. The S. aureus TCA cycle is derepressed upon depletion of rapidly catabolizable carbon sources; this coincides with the transition to producing only formylated delta -toxin and results in an increased inflammatory response. The proinflammatory response should increase host cell damage and result in the release of nutrients. Taken together, these results establish that there is an important linkage between bacterial metabolism and pathogenesis. JF - Journal of Bacteriology AU - Somerville, G A AU - Cockayne, A AU - Duerr, M AU - Peschel, A AU - Otto, M AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, gsomerville@niaid.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 6686 EP - 6694 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 185 IS - 22 SN - 0021-9193, 0021-9193 KW - delta -toxin KW - formyl-methionine KW - formylation KW - peptide deformylase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - N 14400:General KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18888356?accountid=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=Synthesis+and+Deformylation+of+Staphylococcus+aureus+delta+-Toxin+Are+Linked+to+Tricarboxylic+Acid+Cycle+Activity&rft.au=Somerville%2C+G+A%3BCockayne%2C+A%3BDuerr%2C+M%3BPeschel%2C+A%3BOtto%2C+M%3BMusser%2C+J+M&rft.aulast=Somerville&rft.aufirst=G&rft.date=2003-11-01&rft.volume=185&rft.issue=22&rft.spage=6686&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.185.22.6686-6694.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.185.22.6686-6694.2003 ER - TY - JOUR T1 - Phosphatidylcholine-Specific Phospholipase C and Sphingomyelinase Activities in Bacteria of the Bacillus cereus Group AN - 18886779; 5741099 AB - Bacillus anthracis is nonhemolytic, even though it is closely related to the highly hemolytic Bacillus cereus. Hemolysis by B. cereus results largely from the action of phosphatidylcholine-specific phospholipase C (PC-PLC) and sphingomyelinase (SPH), encoded by the plc and sph genes, respectively. In B. cereus, these genes are organized in an operon regulated by the global regulator PlcR. B. anthracis contains a highly similar cereolysin operon, but it is transcriptionally silent because the B. anthracis PlcR is truncated at the C terminus. Here we report the cloning, expression, purification, and enzymatic characterization of PC-PLC and SPH from B. cereus and B. anthracis. We also investigated the effects of expressing PlcR on the expression of plc and sph. In B. cereus, PlcR was found to be a positive regulator of plc but a negative regulator of sph. Replacement of the B. cereus plcR gene by its truncated orthologue from B. anthracis eliminated the activities of both PC-PLC and SPH, whereas introduction into B. anthracis of the B. cereus plcR gene with its own promoter did not activate cereolysin expression. Hemolytic activity was detected in B. anthracis strains containing the B. cereus plcR gene on a multicopy plasmid under control of the strong B. anthracis protective antigen gene promoter or in a strain carrying a multicopy plasmid containing the entire B. cereus plc-sph operon. Slight hemolysis and PC-PLC activation were found when PlcR-producing B. anthracis strains were grown under anaerobic-plus-CO sub(2) or especially under aerobic-plus-CO sub(2) conditions. Unmodified parental B. anthracis strains did not demonstrate obvious hemolysis under the same conditions. JF - Infection and Immunity AU - Pomerantsev AU - Kalnin, K V AU - Osorio, M AU - Leppla, SH AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-4350, sleppla@niaid.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 6591 EP - 6606 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 71 IS - 11 SN - 0019-9567, 0019-9567 KW - Phosphatidylcholine KW - PlcR protein KW - Sphingomyelinase A KW - plc gene KW - sph gene KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18886779?accountid=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=Phosphatidylcholine-Specific+Phospholipase+C+and+Sphingomyelinase+Activities+in+Bacteria+of+the+Bacillus+cereus+Group&rft.au=Pomerantsev%3BKalnin%2C+K+V%3BOsorio%2C+M%3BLeppla%2C+SH&rft.aulast=Pomerantsev&rft.aufirst=&rft.date=2003-11-01&rft.volume=71&rft.issue=11&rft.spage=6591&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.71.11.6591-6606.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.71.11.6591-6606.2003 ER - TY - JOUR T1 - Lifestyle Risk Factors and Chronic Kidney Disease AN - 17904869; 5868406 AB - To examine the effects of lifestyle risk factors such as alcohol consumption, cigarette smoking and body mass index (BMI) on the development of chronic kidney disease. We used a case-control study of 554 hospital cases and 516 age, race, and gender-matched community controls. The main outcome measure was newly-diagnosed chronic kidney disease, assessed by chart review. Self-reported history of alcohol consumption, smoking, and BMI as well as other co-variables were obtained during telephone interviews. Logistic regression models assessed the association between lifestyle risk factors and chronic kidney disease and were adjusted for important co-variables. We found no significant associations between alcohol consumption and chronic kidney disease, with the exception of moonshine, which resulted in an increased risk of chronic kidney disease (including all subtypes). The effects of smoking on chronic kidney disease were inconsistent, but pointed to no appreciable excess risk among smokers. Increasing quartiles of BMI were positively and significantly associated with nephrosclerosis (ORs [95% CI]: 2.5 [1.0-6.0], 2.8 [1.2-6.8] and 4.6 [1.8-11.6], for the second, third, and fourth quartiles of BMI, respectively). Our study revealed a significant positive association between BMI and nephrosclerosis. We did not find an increased risk of chronic kidney disease associated with alcohol or cigarette smoking. JF - Annals of Epidemiology AU - Vupputuri, S AU - Sandler, D P AD - National Institute of Environmental Health Sciences, Epidemiology Branch, P.O. Box 12233, MD A3-05, Research Triangle Park, NC 27709, USA, vupputu1@niehs.nih.gov Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 712 EP - 720 VL - 13 IS - 10 SN - 1047-2797, 1047-2797 KW - Risk Abstracts KW - Alcohol KW - Cigarette smoking KW - Kidney KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17904869?accountid=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=Annals+of+Epidemiology&rft.atitle=Lifestyle+Risk+Factors+and+Chronic+Kidney+Disease&rft.au=Vupputuri%2C+S%3BSandler%2C+D+P&rft.aulast=Vupputuri&rft.aufirst=S&rft.date=2003-11-01&rft.volume=13&rft.issue=10&rft.spage=712&rft.isbn=&rft.btitle=&rft.title=Annals+of+Epidemiology&rft.issn=10472797&rft_id=info:doi/10.1016%2FS1047-2797%2803%2900066-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Alcohol; Kidney; Cigarette smoking DO - http://dx.doi.org/10.1016/S1047-2797(03)00066-8 ER - TY - JOUR T1 - Effects of Soil Fines and Surfactant Sorption on Contaminant Reduction of Coarse Fractions During Soil Washing AN - 16166905; 5807457 AB - The reduction of contaminants sorbed on the coarse fraction of soils to the level below clean-up requirements is essential for an effective soil washing process. This study investigated the effects of soil texture and surfactant sorption on the reduction of total petroleum hydrocarbons (TPH) in coarse fraction during soil washing. Batch TPH sorption experiments were conducted on soil slurry with various soil fine/coarse ratios and surfactants Octylpheny polyoxyethylene (TX-100) and Dodecylpyridinium chloride (DPC) at the dosage below their saturation levels of sorption. In a sandy loam soil of low silt and clay contents, increasing the fine/coarse ratio from 0.4 to 1.2 without adding surfactants resulted in a reduction of TPH levels in the coarse fraction by 30%. Increasing the fine/coarse ratio along with sorbed surfactant (3000 mg TX-100 or 10,000 mg DPC per kg soil) further reduced TPH concentrations in the coarse fraction. For a silty loam soil already containing a high percentage of fine particles, increasing the fine/coarse ratio from 5.9 to 18.8 without surfactant addition yielded no further TPH reduction in the coarse fraction. On the other hand, surfactant sorption at the fine/coarse ratio of 5.9 improved the washing efficiency of the coarse fraction. These experimental results suggested the importance of high contents of soil fines and surfactant sorption in achieving low contaminant concentrations of coarse fractions during soil washing. JF - Journal of Environmental Science and Health, Part A: Toxic/Hazardous Substances & Environmental Engineering AU - Yeh, CK-J AU - Young, Chao-Ching AD - Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, 1 Hseuh Fu Road, Nei Pu 91207, Pingtung Shien, Taiwan, ROC, kjyeh@mail.npust.edu.tw Y1 - 2003/11// PY - 2003 DA - Nov 2003 SP - 2697 EP - 2709 VL - A38 IS - 11 SN - 1093-4529, 1093-4529 KW - soil washing KW - Pollution Abstracts KW - Soil remediation KW - Sorption KW - Hydrocarbons KW - Petroleum KW - Decontamination KW - Surfactants KW - P 5000:LAND POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16166905?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environmental+Science+and+Health%2C+Part+A%3A+Toxic%2FHazardous+Substances+%26+Environmental+Engineering&rft.atitle=Effects+of+Soil+Fines+and+Surfactant+Sorption+on+Contaminant+Reduction+of+Coarse+Fractions+During+Soil+Washing&rft.au=Yeh%2C+CK-J%3BYoung%2C+Chao-Ching&rft.aulast=Yeh&rft.aufirst=CK-J&rft.date=2003-11-01&rft.volume=A38&rft.issue=11&rft.spage=2697&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Science+and+Health%2C+Part+A%3A+Toxic%2FHazardous+Substances+%26+Environmental+Engineering&rft.issn=10934529&rft_id=info:doi/10.1081%2FESE-120024457 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2004-04-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Soil remediation; Sorption; Hydrocarbons; Petroleum; Decontamination; Surfactants DO - http://dx.doi.org/10.1081/ESE-120024457 ER - TY - JOUR T1 - Evolution and Classification of P-loop Kinases and Related Proteins AN - 19816295; 5771695 AB - Sequences and structures of all P-loop-fold proteins were compared with the aim of reconstructing the principal events in the evolution of P-loop-containing kinases. It is shown that kinases and some related proteins comprise a monophyletic assemblage within the P-loop NTPase fold. An evolutionary classification of these proteins was developed using standard phylogenetic methods, analysis of shared sequence and structural signatures, and similarity-based clustering. This analysis resulted in the identification of approximately 40 distinct protein families within the P-loop kinase class. Most of these enzymes phosphorylate nucleosides and nucleotides, as well as sugars, coenzyme precursors, adenosine 5-phosphosulfate and polynucleotides. In addition, the class includes sulfotransferases, amide bond ligases, pyrimidine and dihydrofolate reductases, and several other families of enzymes that have acquired new catalytic capabilities distinct from the ancestral kinase reaction. Our reconstruction of the early history of the P-loop NTPase fold includes the initial split into the common ancestor of the kinase and the GTPase classes, and the common ancestor of ATPases. This was followed by the divergence of the kinases, which primarily phosphorylated nucleoside monophosphates (NMP), but could have had broader specificity. We provide evidence for the presence of at least two to four distinct P-loop kinases, including distinct forms specific for dNMP and rNMP, and related enzymes in the last universal common ancestor of all extant life forms. Subsequent evolution of kinases seems to have been dominated by the emergence of new bacterial and, to a lesser extent, archaeal families. Some of these enzymes retained their kinase activity but evolved new substrate specificities, whereas others acquired new activities, such as sulfate transfer and reduction. Eukaryotes appear to have acquired most of their kinases via horizontal gene transfer from Bacteria, partly from the mitochondrial and chloroplast endosymbionts and partly at later stages of evolution. A distinct superfamily of kinases, which we designated DxTN after its sequence signature, appears to have evolved in selfish replicons, such as bacteriophages, and was subsequently widely recruited by eukaryotes for multiple functions related to nucleic acid processing and general metabolism. In the course of this analysis, several previously undetected groups of predicted kinases were identified, including widespread archaeo-eukaryotic and archaeal families. The results could serve as a framework for systematic experimental characterization of new biochemical and biological functions of kinases. JF - Journal of Molecular Biology AU - Leipe, D D AU - Koonin, E V AU - Aravind, L AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, aravind@ncbi.nlm.nih.gov Y1 - 2003/10/31/ PY - 2003 DA - 2003 Oct 31 SP - 781 EP - 815 VL - 333 IS - 4 SN - 0022-2836, 0022-2836 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - Phages KW - Sulfotransferase KW - Endosymbionts KW - Substrate specificity KW - Mitochondria KW - polynucleotides KW - Dihydrofolate reductase KW - Coenzymes KW - Phylogeny KW - Sugar KW - Adenosinetriphosphatase KW - Enzymes KW - protein families KW - Chloroplasts KW - Nucleotides KW - Sulfate KW - nucleic acids KW - Gene transfer KW - nucleosides KW - pyrimidines KW - amides KW - Adenosine KW - Metabolism KW - Evolution KW - Guanosinetriphosphatase KW - J 02310:Genetics & Taxonomy KW - V 22320:Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19816295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Evolution+and+Classification+of+P-loop+Kinases+and+Related+Proteins&rft.au=Leipe%2C+D+D%3BKoonin%2C+E+V%3BAravind%2C+L&rft.aulast=Leipe&rft.aufirst=D&rft.date=2003-10-31&rft.volume=333&rft.issue=4&rft.spage=781&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1016%2Fj.jmb.2003.08.040 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Phages; Sulfotransferase; Endosymbionts; Mitochondria; Substrate specificity; polynucleotides; Dihydrofolate reductase; Coenzymes; Phylogeny; Sugar; Adenosinetriphosphatase; protein families; Enzymes; Chloroplasts; Nucleotides; Sulfate; nucleic acids; Gene transfer; nucleosides; pyrimidines; Adenosine; amides; Evolution; Metabolism; Guanosinetriphosphatase DO - http://dx.doi.org/10.1016/j.jmb.2003.08.040 ER - TY - JOUR T1 - Antiphospholipid-protein antibodies and acute ischemic stroke in the NINDS rt-PA Stroke Trial. AN - 71313642; 14581697 JF - Neurology AU - Tanne, D AU - Levine, S R AU - Brey, R L AU - Lin, H AU - Tilley, B C AU - NINDS rt-PA Stroke Study Group AD - Department of Neurology, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Hashomer, Israel. tanne@post.tau.ac.il ; NINDS rt-PA Stroke Study Group Y1 - 2003/10/28/ PY - 2003 DA - 2003 Oct 28 SP - 1158 EP - 1159 VL - 61 IS - 8 KW - Antibodies, Anticardiolipin KW - 0 KW - Antibodies, Antiphospholipid KW - Tissue Plasminogen Activator KW - EC 3.4.21.68 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Acute Disease KW - Cerebral Hemorrhage -- chemically induced KW - Odds Ratio KW - Double-Blind Method KW - Injections, Intravenous KW - Humans KW - Disease Progression KW - Antibodies, Anticardiolipin -- blood KW - Predictive Value of Tests KW - Glasgow Outcome Scale -- statistics & numerical data KW - National Institutes of Health (U.S.) -- statistics & numerical data KW - Treatment Outcome KW - Stroke -- drug therapy KW - Tissue Plasminogen Activator -- therapeutic use KW - Brain Ischemia -- drug therapy KW - Antibodies, Antiphospholipid -- blood KW - Tissue Plasminogen Activator -- adverse effects KW - Stroke -- blood KW - Brain Ischemia -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71313642?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Antiphospholipid-protein+antibodies+and+acute+ischemic+stroke+in+the+NINDS+rt-PA+Stroke+Trial.&rft.au=Tanne%2C+D%3BLevine%2C+S+R%3BBrey%2C+R+L%3BLin%2C+H%3BTilley%2C+B+C%3BNINDS+rt-PA+Stroke+Study+Group&rft.aulast=Tanne&rft.aufirst=D&rft.date=2003-10-28&rft.volume=61&rft.issue=8&rft.spage=1158&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=1526-632X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-24 N1 - Date created - 2003-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Microarray analysis indicates biphasic biological responses of the mouse uterus to acute estradiol are recapitulated in genomic responses AN - 39733978; 3793171 AU - Hewitt, S C AU - Deroo, B J AU - Hansen, K J AU - Collins, J AU - Grissom, S AU - Afshari, C AU - Korach, K S Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39733978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Microarray+analysis+indicates+biphasic+biological+responses+of+the+mouse+uterus+to+acute+estradiol+are+recapitulated+in+genomic+responses&rft.au=Hewitt%2C+S+C%3BDeroo%2C+B+J%3BHansen%2C+K+J%3BCollins%2C+J%3BGrissom%2C+S%3BAfshari%2C+C%3BKorach%2C+K+S&rft.aulast=Hewitt&rft.aufirst=S&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for the Study of Reproduction, 1619 Monroe Street, Madison, WI 53711-2063, USA; phone: 608-256-2777; fax: 608-256-4610; email: ssr@ssr.org; URL: www.ssr.org/. Paper No. 11 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Fgf8 plays a fundamental role in kidney development AN - 39717058; 3789032 AU - Perantoni, A O AU - Timofeeva, O AU - Richman, C AU - Pajni-Underwood, S AU - Lewandoski, M Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39717058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Fgf8+plays+a+fundamental+role+in+kidney+development&rft.au=Perantoni%2C+A+O%3BTimofeeva%2C+O%3BRichman%2C+C%3BPajni-Underwood%2C+S%3BLewandoski%2C+M&rft.aulast=Perantoni&rft.aufirst=A&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 466 B89 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Increased local rates of cerebral protein synthesis in fragile X knockout mice AN - 39715845; 3788956 AU - Qin, M AU - Kang, J AU - Smith, C B Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39715845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Increased+local+rates+of+cerebral+protein+synthesis+in+fragile+X+knockout+mice&rft.au=Qin%2C+M%3BKang%2C+J%3BSmith%2C+C+B&rft.aulast=Qin&rft.aufirst=M&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 390 B13 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - bHLH-Zip transcription factor Mitf is conserved in Drosophila and is expressed in the developing eye AN - 39714336; 3789112 AU - Hallsson, J H AU - Haflidadsttir, B S AU - Stivers, C AU - Odenwald, W AU - Pignoni, F AU - Arnheiter, H AU - Steingrimsson, E Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39714336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=bHLH-Zip+transcription+factor+Mitf+is+conserved+in+Drosophila+and+is+expressed+in+the+developing+eye&rft.au=Hallsson%2C+J+H%3BHaflidadsttir%2C+B+S%3BStivers%2C+C%3BOdenwald%2C+W%3BPignoni%2C+F%3BArnheiter%2C+H%3BSteingrimsson%2C+E&rft.aulast=Hallsson&rft.aufirst=J&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 549 B172 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - BMP signaling to the AER is required for interdigital cell death during limb development AN - 39714199; 3789242 AU - Underwood, S P AU - Wilson, C AU - Mishina, Y AU - Lewandoski, M Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39714199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=BMP+signaling+to+the+AER+is+required+for+interdigital+cell+death+during+limb+development&rft.au=Underwood%2C+S+P%3BWilson%2C+C%3BMishina%2C+Y%3BLewandoski%2C+M&rft.aulast=Underwood&rft.aufirst=S&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 680 B303 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Cloning, embryonic expression analysis and targeting of the mouse Gbx1 gene AN - 39711821; 3788774 AU - Waters, ST AU - Wilson, C P AU - Lewandoski, M Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39711821?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Cloning%2C+embryonic+expression+analysis+and+targeting+of+the+mouse+Gbx1+gene&rft.au=Waters%2C+ST%3BWilson%2C+C+P%3BLewandoski%2C+M&rft.aulast=Waters&rft.aufirst=ST&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 229 B222 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Regulation of cell and tissue polarity by Daam and Wnt signaling AN - 39711386; 3788622 AU - Nakaya, M AU - Habas, R AU - He, X AU - Yamaguchi, T P Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39711386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Regulation+of+cell+and+tissue+polarity+by+Daam+and+Wnt+signaling&rft.au=Nakaya%2C+M%3BHabas%2C+R%3BHe%2C+X%3BYamaguchi%2C+T+P&rft.aulast=Nakaya&rft.aufirst=M&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 77 B70 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Axon segmental border crossing in the Drosophila CNS is regulated by nerfin-1 AN - 39708869; 3788826 AU - Kuzin, A AU - Stivers, C AU - Brody, T AU - Odenwald, W Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39708869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Axon+segmental+border+crossing+in+the+Drosophila+CNS+is+regulated+by+nerfin-1&rft.au=Kuzin%2C+A%3BStivers%2C+C%3BBrody%2C+T%3BOdenwald%2C+W&rft.aulast=Kuzin&rft.aufirst=A&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 281 B274 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Differentiation and patterning of developing blood vessels-insights from the zebrafish AN - 39700639; 3788934 AU - Weinstein, B Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39700639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Differentiation+and+patterning+of+developing+blood+vessels-insights+from+the+zebrafish&rft.au=Weinstein%2C+B&rft.aulast=Weinstein&rft.aufirst=B&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Dysautonomia in Parkinson's disease AN - 39698837; 3787693 AU - Goldstein, D S Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39698837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Dysautonomia+in+Parkinson%27s+disease&rft.au=Goldstein%2C+D+S&rft.aulast=Goldstein&rft.aufirst=D&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Kenes Intl., 17, rue du Cendrier, P.O. Box 1726, CH-1211 Geneva 1, Switzerland; phone: 41 (022) 908 04 88; fax: 41 (022) 732 28 50; email: adpd@kenes.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Cloning and characterization of the 5-flanking region for the Ehox gene AN - 39698469; 3788654 AU - Lee, W K AU - Kim, Y-M AU - Malik, N AU - Ma, C AU - Westphal, H Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39698469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Feminist+Review&rft.atitle=making+feminist+sense+of+no-platforming&rft.au=O%27keefe%2C+Theresa&rft.aulast=O%27keefe&rft.aufirst=Theresa&rft.date=2016-07-01&rft.volume=&rft.issue=113&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Feminist+Review&rft.issn=01417789&rft_id=info:doi/10.1057%2Ffr.2016.7 LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 109 B102 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Search for targets of the Drosophila neuroblast temporal network AN - 39662557; 3788638 AU - Brody, T AU - Stivers, C AU - Russ, D AU - Stevenson, C AU - Odenwald, W F Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39662557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Search+for+targets+of+the+Drosophila+neuroblast+temporal+network&rft.au=Brody%2C+T%3BStivers%2C+C%3BRuss%2C+D%3BStevenson%2C+C%3BOdenwald%2C+W+F&rft.aulast=Brody&rft.aufirst=T&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 93 B86 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Two transgenic zebrafish be involved with Notch signaling; hsp-Mib:EGFP and pher4:EGFP AN - 39662521; 3788617 AU - Yeo, S-Y AU - Chitnis, A Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39662521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Two+transgenic+zebrafish+be+involved+with+Notch+signaling%3B+hsp-Mib%3AEGFP+and+pher4%3AEGFP&rft.au=Yeo%2C+S-Y%3BChitnis%2C+A&rft.aulast=Yeo&rft.aufirst=S-Y&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 72 B65 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Allelic series of mutants in phospholipase C-gamma-1 reveals its requirement for arterial development in zebrafish AN - 39656659; 3788629 AU - Covassin, L AU - Bakis, M AU - Weinstein, B AU - Lawson, N Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39656659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Allelic+series+of+mutants+in+phospholipase+C-gamma-1+reveals+its+requirement+for+arterial+development+in+zebrafish&rft.au=Covassin%2C+L%3BBakis%2C+M%3BWeinstein%2C+B%3BLawson%2C+N&rft.aulast=Covassin&rft.aufirst=L&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 84 B77 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - BMP signaling regulates mesoderm patterning in mouse embryogenesis AN - 39617993; 3788847 AU - Miura, S AU - Davis, S AU - Klingensmith, J AU - Mishina, Y Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39617993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=BMP+signaling+regulates+mesoderm+patterning+in+mouse+embryogenesis&rft.au=Miura%2C+S%3BDavis%2C+S%3BKlingensmith%2C+J%3BMishina%2C+Y&rft.aulast=Miura&rft.aufirst=S&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 302 B295 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Hypomorphic and normal expression of a point mutated NMHC II-B results in distinct phenotypes in mice AN - 39617955; 3789226 AU - Ma, X AU - Kawamoto, S AU - Adelstein, R S Y1 - 2003/10/21/ PY - 2003 DA - 2003 Oct 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39617955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Hypomorphic+and+normal+expression+of+a+point+mutated+NMHC+II-B+results+in+distinct+phenotypes+in+mice&rft.au=Ma%2C+X%3BKawamoto%2C+S%3BAdelstein%2C+R+S&rft.aulast=Ma&rft.aufirst=X&rft.date=2003-10-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Developmental Biology, URL: sdb.bio.purdue.edu. Paper No. 664 B287 N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Multiple myeloma and diesel and other occupational exposures in swedish construction workers. AN - 73511104; 12925968 AB - We examined the relationships between occupational exposures and the risk of multiple myeloma among male construction workers in Sweden. A total of 446 myeloma subjects were identified among 365,424 male workers followed from 1971 to 1999. Occupational exposure was assessed using a semiquantitative job-exposure matrix, based on a survey carried out by the Construction Industry's Organization for Working Environment, Occupational Safety and Health in Sweden. Rate ratios (RRs) in the exposed groups relative to the unexposed groups were estimated by Poisson regression. We found an increased risk (RR = 1.3, 95% CI 1.04-1.71) among construction workers exposed to diesel exhaust. Adjustment for other occupational exposures did not change this estimate (RR = 1.3, 95% CI 1.00-1.77). However, there was no monotonic increase in risk with estimated level of exposure (RR for low = 1.4, moderate = 1.1, high = 1.4). There was no evidence of increased risk associated with the other occupational exposures among these construction workers, including asbestos, asphalt, cement dust, metal dust, mineral wool, organic solvents, stone dust and wood dust. Occupational exposure to diesel exhaust in the Swedish construction industry may present a small risk of multiple myeloma, but lack of an exposure-response trend tempers our ability to draw clear conclusions. Copyright 2003 Wiley-Liss, Inc. JF - International journal of cancer AU - Lee, Won Jin AU - Baris, Dalsu AU - Järvholm, Bengt AU - Silverman, Debra T AU - Bergdahl, Ingvar A AU - Blair, Aaron AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. Leewj@mail.nih.gov Y1 - 2003/10/20/ PY - 2003 DA - 2003 Oct 20 SP - 134 EP - 138 VL - 107 IS - 1 SN - 0020-7136, 0020-7136 KW - Hydrocarbons KW - 0 KW - Vehicle Emissions KW - asphalt KW - 8052-42-4 KW - Index Medicus KW - Risk Factors KW - Humans KW - Cohort Studies KW - Sweden -- epidemiology KW - Aged KW - Middle Aged KW - Facility Design and Construction KW - Body Mass Index KW - Male KW - Multiple Myeloma -- etiology KW - Multiple Myeloma -- epidemiology KW - Occupational Diseases -- etiology KW - Occupational Exposure -- adverse effects KW - Occupational Diseases -- epidemiology KW - Vehicle Emissions -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73511104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Multiple+myeloma+and+diesel+and+other+occupational+exposures+in+swedish+construction+workers.&rft.au=Lee%2C+Won+Jin%3BBaris%2C+Dalsu%3BJ%C3%A4rvholm%2C+Bengt%3BSilverman%2C+Debra+T%3BBergdahl%2C+Ingvar+A%3BBlair%2C+Aaron&rft.aulast=Lee&rft.aufirst=Won&rft.date=2003-10-20&rft.volume=107&rft.issue=1&rft.spage=134&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 - 2003-10-09 N1 - Date created - 2003-08-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Int J Cancer. 2005 Apr 10;114(3):501 [15578705] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of Werner syndrome helicase activity by benzo[c]phenanthrene diol epoxide dA adducts in DNA is both strand-and stereoisomer-dependent. AN - 71288232; 12881525 AB - Helicases are among the first enzymes to encounter DNA damage during DNA processing within the cell and thus are likely to be targets for the adverse effects of DNA lesions induced by environmental chemicals. Here we examined the effect of cis- and trans-opened 3,4-diol 1,2-epoxide (DE) DNA adducts of benzo[c]phenanthrene (BcPh) at N6 of adenine on helicase activity. These adducts are derived from the highly tumorigenic (-)-(1R,2S,3S,4R)-DE as well as its less carcinogenic (+)-(1S,2R,3R,4S)-DE enantiomer in both of which the benzylic 4-hydroxyl group and epoxide oxygen are trans. The hydrocarbon portions of these adducts intercalate into DNA on the 3' or the 5' side of the adducted deoxyadenosine for the 1S- and 1R-adducts, respectively. These adducts inhibited the human Werner (WRN) syndrome helicase activity in a strand-specific and stereospecific manner. In the strand along which WRN translocates, cis-opened adducts were significantly more effective inhibitors than trans-opened isomers, indicating that WRN unwinding is sensitive to adduct stereochemistry. WRN helicase activity was also inhibited but to a lesser extent by cis-opened BcPh DE adducts in the displaced strand independent of their direction of intercalation, whereas inhibition by the trans-opened stereoisomers in the displaced strand depended on their orientation, such that only adducts oriented toward the advancing helicase inhibited WRN activity. A BcPh DE adduct positioned in the helicase-translocating strand did not sequester WRN, nor affect the rate of ATP hydrolysis relative to an unadducted control. Although the Bloom (BLM) syndrome helicase was also inhibited by a cis-opened adduct in a strand-specific manner, this helicase was not as severely affected as WRN. Because BcPh DEs form substantial amounts of deoxyadenosine adducts at dA, their adverse effects on helicases could contribute to genetic damage and cell transformation induced by these DEs. Thus, the unwinding activity of RecQ helicases is sensitive to the strand, orientation, and stereochemistry of intercalated polycyclic aromatic hydrocarbon adducts. JF - The Journal of biological chemistry AU - Driscoll, Henry C AU - Matson, Steven W AU - Sayer, Jane M AU - Kroth, Heiko AU - Jerina, Donald M AU - Brosh, Robert M AD - Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, DHHS, Baltimore, Maryland 21224-6825, USA. Y1 - 2003/10/17/ PY - 2003 DA - 2003 Oct 17 SP - 41126 EP - 41135 VL - 278 IS - 42 SN - 0021-9258, 0021-9258 KW - DNA Adducts KW - 0 KW - Oligonucleotides KW - Phenanthrenes KW - Recombinant Proteins KW - benzo(c)phenanthrene 3,4-dihydrodiol KW - 73093-19-3 KW - benzo(c)phenanthrene 1,2-dihydrodiol KW - 73093-22-8 KW - DNA KW - 9007-49-2 KW - Exodeoxyribonucleases KW - EC 3.1.- KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - RECQL protein, human KW - RecQ protein, E coli KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - WRN protein, human KW - Werner Syndrome Helicase KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Escherichia coli -- metabolism KW - Dose-Response Relationship, Drug KW - DNA -- metabolism KW - Humans KW - Adenosine Triphosphatases -- metabolism KW - Oligonucleotides -- metabolism KW - Hydrolysis KW - Insects KW - Baculoviridae KW - Recombinant Proteins -- metabolism KW - Oligonucleotides -- chemistry KW - Kinetics KW - Binding, Competitive KW - Models, Chemical KW - Adenosine Triphosphatases -- chemistry KW - Protein Transport KW - DNA Helicases -- metabolism KW - DNA Helicases -- antagonists & inhibitors KW - Phenanthrenes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71288232?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+Werner+syndrome+helicase+activity+by+benzo%5Bc%5Dphenanthrene+diol+epoxide+dA+adducts+in+DNA+is+both+strand-and+stereoisomer-dependent.&rft.au=Driscoll%2C+Henry+C%3BMatson%2C+Steven+W%3BSayer%2C+Jane+M%3BKroth%2C+Heiko%3BJerina%2C+Donald+M%3BBrosh%2C+Robert+M&rft.aulast=Driscoll&rft.aufirst=Henry&rft.date=2003-10-17&rft.volume=278&rft.issue=42&rft.spage=41126&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 - 2003-12-03 N1 - Date created - 2003-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Receptor glycosylation regulates Ly-49 binding to MHC class I. AN - 75758495; 14530347 AB - Murine NK cells express the Ly-49 family of class I MHC-binding receptors that control their ability to lyse tumor or virally infected host target cells. X-ray crystallography studies have identified two predominant contact sites (sites 1 and 2) that are involved in the binding of the inhibitory receptor, Ly-49A, to H-2D(d). Ly-49G2 (inhibitory) and Ly-49D (activating) are highly homologous to Ly-49A and also recognize H-2D(d). However, the binding of Ly-49D and G(2) to H-2D(d) is of lower affinity than Ly-49A. All Ly-49s contain N-glycosylation motifs; however, the importance of receptor glycosylation in Ly-49-class I interactions has not been determined. Ly-49D and G(2) contain a glycosylation motif (NTT (221-223)), absent in Ly-49A, adjacent to one of the proposed binding sites for H-2D(d) (site 2). The presence of a complex carbohydrate group at this critical site could interfere with class I binding. In this study, we are able to demonstrate for the first time that Ly-49D binds H-2D(d) in the presence of mouse beta(2)-microglobulin. We also demonstrate that glycosylation of the NTT (221-23) motif of Ly-49D inteferes with recognition of H-2D(d). Alteration of the Ly-49D-NTT (221-23) motif to abolish glycosylation at this site resulted in enhanced H-2D(d) binding and receptor activation. Furthermore, glycosylation of Ly-49G2 at NTT (221-23) also reduces receptor binding to H-2D(d) tetramers. Therefore, the addition of complex carbohydrates to the Ly-49 family of receptors may represent a mechanism by which NK cells regulate affinity for host class I ligands. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Mason, Llewellyn H AU - Willette-Brown, Jami AU - Anderson, Stephen K AU - Alvord, W Gregory AU - Klabansky, Richard L AU - Young, Howard A AU - Ortaldo, John R AD - Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute-Clinical Cancer Research, National Institutes of Health, Frederick, MD 21702-1201, USA. MasonL@mail.ncifcrf.gov Y1 - 2003/10/15/ PY - 2003 DA - 2003 Oct 15 SP - 4235 EP - 4242 VL - 171 IS - 8 SN - 0022-1767, 0022-1767 KW - Antigens, Ly KW - 0 KW - Cross-Linking Reagents KW - H-2 Antigens KW - Histocompatibility Antigen H-2D KW - Histocompatibility Antigens Class I KW - Interleukin-2 KW - Lectins, C-Type KW - Receptors, Immunologic KW - Receptors, NK Cell Lectin-Like KW - Arginine KW - 94ZLA3W45F KW - Ribonucleases KW - EC 3.1.- KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Amino Acid Motifs -- immunology KW - Arginine -- metabolism KW - Humans KW - Jurkat Cells KW - Cross-Linking Reagents -- metabolism KW - Glycosylation KW - Mutagenesis, Site-Directed KW - Amino Acid Substitution -- genetics KW - Molecular Sequence Data KW - Amino Acid Substitution -- immunology KW - Amino Acid Motifs -- genetics KW - Up-Regulation -- genetics KW - Amino Acid Sequence KW - Mice KW - Protein Binding -- immunology KW - Arginine -- genetics KW - Transfection KW - Ribonucleases -- genetics KW - Protein Binding -- genetics KW - Up-Regulation -- immunology KW - Gene Targeting KW - Interleukin-2 -- secretion KW - Receptors, Immunologic -- genetics KW - Receptors, Immunologic -- immunology KW - Antigens, Ly -- genetics KW - Histocompatibility Antigens Class I -- metabolism KW - Receptors, Immunologic -- metabolism KW - Antigens, Ly -- metabolism KW - H-2 Antigens -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75758495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Receptor+glycosylation+regulates+Ly-49+binding+to+MHC+class+I.&rft.au=Mason%2C+Llewellyn+H%3BWillette-Brown%2C+Jami%3BAnderson%2C+Stephen+K%3BAlvord%2C+W+Gregory%3BKlabansky%2C+Richard+L%3BYoung%2C+Howard+A%3BOrtaldo%2C+John+R&rft.aulast=Mason&rft.aufirst=Llewellyn&rft.date=2003-10-15&rft.volume=171&rft.issue=8&rft.spage=4235&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 - 2004-01-06 N1 - Date created - 2003-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene array analysis of the hepatic response to endotoxin in glutathione peroxidase-deficient mice. AN - 73589955; 12927356 AB - Glutathione peroxidase-1 (Gpx1) is a major defense enzyme against peroxides. Gpx1-deficient mice (Gpx1-/-) are more susceptible than wild-type (WT) mice to neutrophil-induced oxidant stress and liver injury produced by 700 mg/kg galactosamine and 10 microg/kg endotoxin (Gal/ET). However, it is unclear if Gal/ET modulates redox-sensitive genes in Gpx1-/- mice before the injury. Hepatic RNA was isolated 1.5 and 6 h after Gal/ET administration and subjected to gene expression analysis using Clontech customer-designed mouse toxicology array (600-gene). Gal/ET induced a significant increase in the expression of genes encoding inflammatory response, oxidative stress, growth arrest and responses to DNA damage and/or its repair. In general, more marked alterations were seen in Gpx1-/- as compared with WT mice, supporting the role of Gpx1 in cellular defense against oxidant stress to cope with aberrant gene expression. However, comparison with previous functional studies indicated that not all changes of gene expression are relevant for the pathophysiology. Thus, only a combination of gene array analysis with functional studies allows valid conclusions regarding mechanisms of cell injury. JF - Toxicology letters AU - Li, Chengxiu AU - Liu, Jie AU - Waalkes, Michael P AU - Jaeschke, Hartmut AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis NCI at NIEHS, Research Triangle Park, NC 27709, USA. Y1 - 2003/10/15/ PY - 2003 DA - 2003 Oct 15 SP - 397 EP - 406 VL - 144 IS - 3 SN - 0378-4274, 0378-4274 KW - Endotoxins KW - 0 KW - RNA KW - 63231-63-0 KW - glutathione peroxidase GPX1 KW - EC 1.11.1.- KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Index Medicus KW - Animals KW - DNA Repair KW - Neutrophils KW - DNA Damage KW - Liver KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Knockout KW - Inflammation KW - Cell Division KW - Oligonucleotide Array Sequence Analysis KW - Glutathione Peroxidase -- pharmacology KW - Oxidative Stress KW - Gene Expression Regulation KW - Glutathione Peroxidase -- genetics KW - Endotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73589955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Gene+array+analysis+of+the+hepatic+response+to+endotoxin+in+glutathione+peroxidase-deficient+mice.&rft.au=Li%2C+Chengxiu%3BLiu%2C+Jie%3BWaalkes%2C+Michael+P%3BJaeschke%2C+Hartmut&rft.aulast=Li&rft.aufirst=Chengxiu&rft.date=2003-10-15&rft.volume=144&rft.issue=3&rft.spage=397&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-21 N1 - Date created - 2003-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity and carcinogenicity of riddelliine in rats and mice. AN - 73589871; 12927348 AB - These investigations of riddelliine analyzed potential carcinogenesis and the utility of the female-rat/male-mouse design in bioassays and dose-response. Groups of 50 Fischer rats and B6C3F1 mice were gavage-administered riddelliine 5 days per week for 105 weeks. The dose levels for male rats were 0 or 1.0 mg/kg body weight; female rats 0, 0.01, 0.033, 0.1, 0.33, or 1.0 mg/kg; male mice 0, 0.1, 0.3, or 1.0, 3.0 mg/kg; and female mice 0 or 3.0 mg/kg. The dose groups were purposely designed to evaluate the dose-response relationship only in female rats and male mice. In rats, liver hemangiosarcoma, hepatocellular adenoma, and mononuclear cell leukemia were significantly increased in the 1.0 mg/kg male and female dose groups. Non-neoplastic lesions occurred in the liver and kidney of male and female rats. In mice, hemangiosarcomas increased significantly in the liver of males in the 3.0 mg/kg dose group. Alveolar/bronchiolar neoplasms in the 3.0 mg/kg dose group of female mice were significantly increased. Hepatocellular neoplasms were significantly decreased in the 1.0 mg/kg dose group of male and 3.0 mg/kg dose groups of male and female mice. Non-neoplastic lesions occurred in the liver and kidney of male and female, and lung and arteries of female mice. These studies demonstrate toxicity and carcinogenicity of riddelliine in rats and mice, and a dose-response relationship in female rats and male mice under the experimental conditions employed. JF - Toxicology letters AU - Chan, Po C AU - Haseman, Joseph K AU - Prejean, J D AU - Nyska, Abraham AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709-9998, USA. chanp@niehs.nih.gov Y1 - 2003/10/15/ PY - 2003 DA - 2003 Oct 15 SP - 295 EP - 311 VL - 144 IS - 3 SN - 0378-4274, 0378-4274 KW - Carcinogens KW - 0 KW - Pyrrolizidine Alkaloids KW - riddelliine KW - 23246-96-0 KW - Index Medicus KW - Animals KW - Hemangiosarcoma -- veterinary KW - Liver -- pathology KW - Liver Neoplasms -- veterinary KW - Kidney -- pathology KW - Leukemia -- chemically induced KW - Sex Factors KW - Dose-Response Relationship, Drug KW - Liver Neoplasms -- chemically induced KW - Kidney -- drug effects KW - Mice KW - Hemangiosarcoma -- chemically induced KW - Rats KW - Rats, Inbred F344 KW - Carcinoma, Hepatocellular -- veterinary KW - Leukemia -- veterinary KW - Liver -- drug effects KW - Male KW - Carcinoma, Hepatocellular -- chemically induced KW - Female KW - Carcinogens -- toxicity KW - Pyrrolizidine Alkaloids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73589871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Toxicity+and+carcinogenicity+of+riddelliine+in+rats+and+mice.&rft.au=Chan%2C+Po+C%3BHaseman%2C+Joseph+K%3BPrejean%2C+J+D%3BNyska%2C+Abraham&rft.aulast=Chan&rft.aufirst=Po&rft.date=2003-10-15&rft.volume=144&rft.issue=3&rft.spage=295&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-21 N1 - Date created - 2003-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intracytoplasmic tagging of cells with ferumoxides and transfection agent for cellular magnetic resonance imaging after cell transplantation: methods and techniques. AN - 71297891; 14557764 AB - Superparamagnetic iron oxides (SPIO) are being used to label cells for in vivo monitoring by magnetic resonance imaging (MRI). The purpose of this study is to present protocols using SPIO and a polycationic transfection agent for magnetic labeling of cells as a basis for cellular MRI. Various concentrations of ferumoxides (FE)-poly-l-lysine (PLL) complexes were used to magnetically label cells. Iron incorporation into cells along with cell viability and short- and long-term toxicity were evaluated. Rapidly growing cell suspension and adherent cells were effectively labeled by means of endocytosis into endosomes at low concentrations of FE (25 microg/mL media) and PLL (0.75 microg/mL media). Hematopoietic stem cells and lymphocytes required higher concentrations of PLL (1.5 microg/mL) in serum-free media during initial FE-PLL complex formation before labeling the cells in culture. Total iron concentration in cells depended on the cell type, concentration of FE-PLL complexes in media, cellular density, and incubation time. Iron concentrations after overnight incubation with given FE at 25 microg/mL media resulted in, for example, T cells being labeled with 1 to 3 pg/cell of intracytoplasmic endosomal iron and 15 to 20 pg/cell of intracytoplasmic iron in mesenchymal stem cells compared with 0.01 to 0.1 pg/cell for unlabeled cells. Protocols developed for this study demonstrated no adverse effect on the cell viability, functional capacity, or toxicity. This technique can be used to label cells for in vivo MRI tracking of stem cells and lymphocytes. FE at a concentration of 25 to 50 microg/mL with a ratio of SPIO to PLL of 1:0.03 to 1:0.06 would be sufficient to label cells for cellular MRI. JF - Transplantation AU - Arbab, Ali S AU - Bashaw, Lindsey A AU - Miller, Bradley R AU - Jordan, Elaine K AU - Bulte, Jeff W M AU - Frank, Joseph A AD - Experimental Neuroimaging Section, Laboratory of Diagnostic Radiology Research, National Institutes of Health, Bethesda, MD 20892, USA. saali@cc.nih.gov. Y1 - 2003/10/15/ PY - 2003 DA - 2003 Oct 15 SP - 1123 EP - 1130 VL - 76 IS - 7 SN - 0041-1337, 0041-1337 KW - Coloring Agents KW - 0 KW - Dextrans KW - Drug Combinations KW - Ferrocyanides KW - Indicators and Reagents KW - Magnetite Nanoparticles KW - Oxides KW - Polylysine KW - 25104-18-1 KW - Iron KW - E1UOL152H7 KW - ferumoxides KW - G6N3J05W84 KW - ferric ferrocyanide KW - TLE294X33A KW - Ferrosoferric Oxide KW - XM0M87F357 KW - Index Medicus KW - Osmolar Concentration KW - Animals KW - Neoplasms -- diagnosis KW - Cytoplasm -- metabolism KW - Humans KW - Cell Differentiation KW - Time Factors KW - Magnetic Resonance Imaging KW - Polylysine -- pharmacokinetics KW - Cell Survival -- drug effects KW - Iron -- pharmacokinetics KW - Oxides -- pharmacokinetics KW - Cell Transplantation KW - Iron -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71297891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transplantation&rft.atitle=Intracytoplasmic+tagging+of+cells+with+ferumoxides+and+transfection+agent+for+cellular+magnetic+resonance+imaging+after+cell+transplantation%3A+methods+and+techniques.&rft.au=Arbab%2C+Ali+S%3BBashaw%2C+Lindsey+A%3BMiller%2C+Bradley+R%3BJordan%2C+Elaine+K%3BBulte%2C+Jeff+W+M%3BFrank%2C+Joseph+A&rft.aulast=Arbab&rft.aufirst=Ali&rft.date=2003-10-15&rft.volume=76&rft.issue=7&rft.spage=1123&rft.isbn=&rft.btitle=&rft.title=Transplantation&rft.issn=00411337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-02 N1 - Date created - 2003-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vanadium-induced STAT-1 activation in lung myofibroblasts requires H2O2 and P38 MAP kinase. AN - 71289067; 14556849 AB - Vanadium compounds present in air pollution particulate matter activate signal transduction pathways in pulmonary cell types leading to pathological outcomes including aberrant cell proliferation, apoptosis, and cytokine expression. Vanadium has been proposed to activate transcription factors via the generation of hydrogen peroxide (H2O2). We investigated the mechanisms through which vanadium pentoxide (V2O5), the major form of vanadium released from the industrial burning of fuel oil, activated the signal transducer and activator of transcription (STAT)-1. V2O5-induced STAT-1 activation was blocked by catalase and N-acetyl-L-cysteine (NAC), suggesting vanadium-induced generation of H2O2. Surprisingly, however, V2O5 did not increase H2O2 levels released by rat lung myofibroblasts into cell culture supernatants. Instead, these quiescent myofibroblasts spontaneously released micromolar concentrations of H2O2, and the addition of V2O5 reduced H2O2 levels in cell culture supernatants within minutes. V2O5 suppressed H2O2 for as long as 24 h. Differences in the temporal activation of STAT-1 and p38 MAPK were observed following V2O5 or H2O2 treatment, and STAT-1 activation by V2O5 or H2O2 was attenuated by an inhibitor of the EGF receptor tyrosine kinase (AG1478) or p38 MAPK (SB203580). The phosphorylation of p38 MAPK by V2O5 was inhibited by NAC and catalase, yet the EGF receptor inhibitor AG1478 had no effect on V2O5-induced p38 MAPK activation. Collectively, our findings support the novel hypothesis that H2O2 spontaneously generated by myofibroblasts fuels vanadium-induced activation of STAT-1. Moreover, p38 MAPK and EGF receptor activation are required for V2O5-induced STAT-1 activation. JF - Free radical biology & medicine AU - Wang, Yi-Zhe AU - Ingram, Jennifer L AU - Walters, Dianne M AU - Rice, Annette B AU - Santos, Janine H AU - Van Houten, Bennett AU - Bonner, James C AD - Laboratory of Pulmonary Pathobiology, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2003/10/15/ PY - 2003 DA - 2003 Oct 15 SP - 845 EP - 855 VL - 35 IS - 8 SN - 0891-5849, 0891-5849 KW - DNA-Binding Proteins KW - 0 KW - Enzyme Inhibitors KW - STAT1 Transcription Factor KW - Stat1 protein, rat KW - Trans-Activators KW - Vanadium Compounds KW - Carbon KW - 7440-44-0 KW - Hydrogen Peroxide KW - BBX060AN9V KW - vanadium pentoxide KW - BVG363OH7A KW - Catalase KW - EC 1.11.1.6 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Rats KW - Fibroblasts -- drug effects KW - Animals KW - Receptor, Epidermal Growth Factor -- metabolism KW - Carbon -- adverse effects KW - Enzyme Inhibitors -- pharmacology KW - Acetylcysteine -- pharmacology KW - Fibroblasts -- metabolism KW - Catalase -- pharmacology KW - Phosphorylation -- drug effects KW - Vanadium Compounds -- pharmacology KW - Trans-Activators -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Hydrogen Peroxide -- metabolism KW - Lung -- cytology KW - Lung -- drug effects KW - Lung -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71289067?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Vanadium-induced+STAT-1+activation+in+lung+myofibroblasts+requires+H2O2+and+P38+MAP+kinase.&rft.au=Wang%2C+Yi-Zhe%3BIngram%2C+Jennifer+L%3BWalters%2C+Dianne+M%3BRice%2C+Annette+B%3BSantos%2C+Janine+H%3BVan+Houten%2C+Bennett%3BBonner%2C+James+C&rft.aulast=Wang&rft.aufirst=Yi-Zhe&rft.date=2003-10-15&rft.volume=35&rft.issue=8&rft.spage=845&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-20 N1 - Date created - 2003-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of the olfactory tubercle in cocaine reward: intracranial self-administration studies. AN - 71286904; 14561857 AB - Cocaine has multiple actions and multiple sites of action in the brain. Evidence from pharmacological studies indicates that it is the ability of cocaine to block dopamine uptake and elevate extracellular dopamine concentrations, and thus increase dopaminergic receptor activation, that makes cocaine rewarding. Lesion studies have implicated the nucleus accumbens (the dorsal portion of the "ventral striatum") as the probable site of the rewarding action of the drug. However, the drug is only marginally self-administered into this site. We now report that cocaine (60 or 200 mm in 75 nl/infusion) is readily self-administered into the olfactory tubercle, the most ventral portion of the ventral striatum. Cocaine (200 mm) was self-administered marginally into the accumbens shell but not into the core, dorsal striatum, or ventral pallidum. In addition, cocaine injections (200 mm in 300 nl) into the tubercle but not the shell or ventral pallidum induced conditioned place preference. Rewarding effects of cocaine in the tubercle were blocked by coadministration of dopamine D1 or D2 antagonists (1 mm SCH 23390 or 3 mm raclopride) and were not mimicked by injections of the local anesthetic procaine (800 mm). In conclusion, the tubercle plays a critical role in mediating rewarding action of cocaine. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Ikemoto, Satoshi AD - Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224, USA. sikemoto@intra.nida.nih.gov Y1 - 2003/10/15/ PY - 2003 DA - 2003 Oct 15 SP - 9305 EP - 9311 VL - 23 IS - 28 KW - Anesthetics, Local KW - 0 KW - Dopamine Antagonists KW - Dopamine D2 Receptor Antagonists KW - Receptors, Dopamine D1 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Rats KW - Behavior, Animal -- drug effects KW - Animals KW - Discrimination (Psychology) -- drug effects KW - Self Administration KW - Anesthetics, Local -- pharmacology KW - Receptors, Dopamine D1 -- antagonists & inhibitors KW - Dopamine Antagonists -- pharmacology KW - Choice Behavior -- drug effects KW - Reinforcement (Psychology) KW - Rats, Wistar KW - Male KW - Drug Administration Routes KW - Reward KW - Olfactory Pathways -- physiology KW - Cocaine-Related Disorders -- physiopathology KW - Cocaine -- pharmacology KW - Olfactory Pathways -- drug effects KW - Cocaine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71286904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Involvement+of+the+olfactory+tubercle+in+cocaine+reward%3A+intracranial+self-administration+studies.&rft.au=Ikemoto%2C+Satoshi&rft.aulast=Ikemoto&rft.aufirst=Satoshi&rft.date=2003-10-15&rft.volume=23&rft.issue=28&rft.spage=9305&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-17 N1 - Date created - 2003-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genotypic Differences in the Chlamydia pneumoniae tyrP Locus Related to Vascular Tropism and Pathogenicity AN - 19173351; 5747369 AB - Chlamydia pneumoniae is an obligate intracellular pathogen that causes respiratory infections and has been associated with cardiovascular disease. We compared respiratory and cardiovascular isolates to find genetic differences associated with pathogenicity. A polymorphic region encoding a tyrosine/tryptophan permease was found to differ between disease isolates. Respiratory strains contained multiple copies of the tyrP gene, and vascular strains contained a single copy. Single-nucleotide polymorphism analysis revealed the duplication to be a phylogenetically old event. Gene amplification was associated with higher mRNA levels and higher uptake of the substrate tyrosine, indicating an amino-acid transport-related phenotype associated with the tyrP genotype. Vascular strains, despite their reduced ability to transport tyrosine, do not appear to have a reduced growth rate in vitro. We hypothesize that the important difference between strains of vascular and respiratory origin may lie in the increased tendency of vascular strains to elicit persistent infection that is triggered by amino-acid starvation. JF - Journal of Infectious Diseases AU - Gieffers, J AU - Durling, L AU - Ouellette, S P AU - Rupp, J AU - Maass, M AU - Byrne, GI AU - Caldwell, H D AU - Belland, R J AD - Laboratory of Intracellular Parasites, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA Y1 - 2003/10/15/ PY - 2003 DA - 2003 Oct 15 SP - 1085 EP - 1093 VL - 188 IS - 8 SN - 0022-1899, 0022-1899 KW - tryptophan permease KW - tyrP gene KW - tyrosine permease KW - Microbiology Abstracts B: Bacteriology KW - Starvation KW - Growth rate KW - Amino acids KW - Pathogenicity KW - Single-nucleotide polymorphism KW - Chlamydia pneumoniae KW - Tropism KW - Pneumonia KW - Respiratory tract KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19173351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Genotypic+Differences+in+the+Chlamydia+pneumoniae+tyrP+Locus+Related+to+Vascular+Tropism+and+Pathogenicity&rft.au=Gieffers%2C+J%3BDurling%2C+L%3BOuellette%2C+S+P%3BRupp%2C+J%3BMaass%2C+M%3BByrne%2C+GI%3BCaldwell%2C+H+D%3BBelland%2C+R+J&rft.aulast=Gieffers&rft.aufirst=J&rft.date=2003-10-15&rft.volume=188&rft.issue=8&rft.spage=1085&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia pneumoniae; Growth rate; Single-nucleotide polymorphism; Tropism; Pathogenicity; Respiratory tract; Amino acids; Starvation; Pneumonia ER - TY - JOUR T1 - Position-specific trapping of topoisomerase II by benzo[a]pyrene diol epoxide adducts: implications for interactions with intercalating anticancer agents. AN - 71275354; 14523238 AB - DNA topoisomerase II (Top2) is the target of some of the most effective anticancer DNA intercalators. To determine the effect of intercalating ligands at defined positions relative to a known DNA cleavage site for human Top2alpha, we synthesized oligodeoxynucleotides containing single trans-opened benzo[a]pyrene 7,8-diol 9,10-epoxide (DE) deoxyadenosine (dA) adducts of known absolute configuration, placed at specific positions in a duplex sequence containing staggered Top2 cleavage sites on both strands. Because the orientations of the intercalated hydrocarbon are known from NMR solution structures of duplex oligonucleotides containing these dA adducts, a detailed analysis of the relationship between the position of intercalation and trapping of Top2 is possible. Our findings demonstrate that (i) Top2 cleavage complexes are trapped by intercalation of the hydrocarbon at either of the staggered cleavage sites or immediately adjacent to the base pairs flanking the cleavage sites within the stagger; (ii) both concerted and nonconcerted cleavage by both subunits of a Top2 homodimer were detected depending on the position of the benzo[a]pyrene DE dA adduct; and (iii) intercalation immediately outside of the staggered Top2 cleavage site, and to a lesser extent in the middle of the stagger, prevents Top2 from cleaving DNA at this site, consistent with the effect of some intercalators as suppressors of Top2-mediated DNA cleavage. These results identify specific binding sites for intercalators that result in trapping of Top2. Such poisoning of Top2 by bulky polycyclic aromatic hydrocarbon DE adducts constitutes a potential mechanism for their carcinogenic activity. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Khan, Qasim A AU - Kohlhagen, Glenda AU - Marshall, Richard AU - Austin, Caroline A AU - Kalena, Govind P AU - Kroth, Heiko AU - Sayer, Jane M AU - Jerina, Donald M AU - Pommier, Yves AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health/DHHS, Building 37, Bethesda, MD 20892, USA. Y1 - 2003/10/14/ PY - 2003 DA - 2003 Oct 14 SP - 12498 EP - 12503 VL - 100 IS - 21 SN - 0027-8424, 0027-8424 KW - Antigens, Neoplasm KW - 0 KW - Antineoplastic Agents KW - DNA Adducts KW - DNA-Binding Proteins KW - Intercalating Agents KW - Recombinant Proteins KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - DNA topoisomerase II alpha KW - Index Medicus KW - Molecular Structure KW - Intercalating Agents -- pharmacology KW - Recombinant Proteins -- drug effects KW - DNA Adducts -- pharmacology KW - DNA Adducts -- chemistry KW - Models, Molecular KW - Humans KW - DNA Adducts -- metabolism KW - Binding Sites KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - In Vitro Techniques KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Antineoplastic Agents -- pharmacology KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- analogs & derivatives KW - DNA Topoisomerases, Type II -- metabolism KW - DNA Topoisomerases, Type II -- drug effects KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- pharmacology KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry KW - DNA Topoisomerases, Type II -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71275354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Position-specific+trapping+of+topoisomerase+II+by+benzo%5Ba%5Dpyrene+diol+epoxide+adducts%3A+implications+for+interactions+with+intercalating+anticancer+agents.&rft.au=Khan%2C+Qasim+A%3BKohlhagen%2C+Glenda%3BMarshall%2C+Richard%3BAustin%2C+Caroline+A%3BKalena%2C+Govind+P%3BKroth%2C+Heiko%3BSayer%2C+Jane+M%3BJerina%2C+Donald+M%3BPommier%2C+Yves&rft.aulast=Khan&rft.aufirst=Qasim&rft.date=2003-10-14&rft.volume=100&rft.issue=21&rft.spage=12498&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 - 2003-12-04 N1 - Date created - 2003-10-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nucleic Acids Res. 2000 May 1;28(9):1947-54 [10756196] Annu Rev Pharmacol Toxicol. 1994;34:191-218 [8042851] Biochemistry. 2000 Nov 21;39(46):14040-53 [11087351] Biochemistry. 2001 Feb 6;40(5):1159-70 [11170441] Biochemistry. 2001 May 22;40(20):5870-81 [11352722] Chem Res Toxicol. 2001 Jun;14(6):708-19 [11409942] Annu Rev Biochem. 2001;70:369-413 [11395412] Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3070-5 [11867721] J Biol Chem. 2002 Apr 19;277(16):13666-72 [11832494] Nat Rev Mol Cell Biol. 2002 Jun;3(6):430-40 [12042765] Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15387-92 [12426403] Curr Top Med Chem. 2003;3(3):321-38 [12570766] J Biol Chem. 2003 Feb 28;278(9):7406-12 [12473657] J Biol Chem. 2003 Mar 14;278(11):9905-11 [12524450] Chem Biol Interact. 1977 Mar;16(3):281-300 [862130] Proc Natl Acad Sci U S A. 1978 Nov;75(11):5358-61 [281685] J Biol Chem. 1984 Jul 25;259(14):9182-7 [6086625] Biochemistry. 1985 Nov 5;24(23):6406-10 [3002439] Biochemistry. 1987 Oct 6;26(20):6402-6 [2827726] Biochemistry. 1989 Jul 25;28(15):6229-36 [2551367] J Virol. 1990 Jan;64(1):419-23 [2152827] Biochemistry. 1990 Mar 13;29(10):2511-5 [2159323] Nucleic Acids Res. 1990 Nov 25;18(22):6611-9 [2174543] J Biol Chem. 1991 Oct 25;266(30):20418-23 [1657924] Nucleic Acids Res. 1991 Nov 11;19(21):5973-80 [1658748] J Mol Biol. 1991 Dec 20;222(4):909-24 [1662289] Biochemistry. 1993 Jan 12;32(1):145-52 [8380330] EMBO J. 1993 May;12(5):2085-97 [8387918] Cancer Res. 1993 Aug 1;53(15):3591-6 [8393377] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11007-11 [7971998] Biochemistry. 1995 Oct 17;34(41):13570-81 [7577946] Science. 1998 Mar 6;279(5356):1504-13 [9488644] Biochim Biophys Acta. 1998 Oct 1;1400(1-3):63-81 [9748506] Biochim Biophys Acta. 1998 Oct 1;1400(1-3):139-54 [9748545] Biochemistry. 1998 Nov 24;37(47):16516-28 [9843418] Nat Struct Biol. 1999 Apr;6(4):322-6 [10201398] Biochim Biophys Acta. 1998 Oct 1;1400(1-3):185-94 [9748568] Nature. 1996 Jan 18;379(6562):225-32 [8538787] Curr Opin Struct Biol. 1996 Feb;6(1):84-90 [8696977] Annu Rev Biochem. 1996;65:635-92 [8811192] Science. 1996 Oct 18;274(5286):430-2 [8832894] Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10739-44 [10995470] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic footprinting of a retroviral Gag gene suggests an important role in virus replication. AN - 71271001; 14530396 JF - Proceedings of the National Academy of Sciences of the United States of America AU - Rein, Alan AD - HIV Drug Resistance Program, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. rein@ncircf.gov Y1 - 2003/10/14/ PY - 2003 DA - 2003 Oct 14 SP - 11929 EP - 11930 VL - 100 IS - 21 SN - 0027-8424, 0027-8424 KW - DNA, Viral KW - 0 KW - Gene Products, gag KW - Index Medicus KW - Gene Products, gag -- genetics KW - Animals KW - DNA Footprinting KW - Gene Products, gag -- chemistry KW - Gene Products, gag -- metabolism KW - DNA, Viral -- genetics KW - Mutagenesis, Insertional KW - Virus Replication -- genetics KW - Moloney murine leukemia virus -- physiology KW - Moloney murine leukemia virus -- genetics KW - Genes, gag UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71271001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Genetic+footprinting+of+a+retroviral+Gag+gene+suggests+an+important+role+in+virus+replication.&rft.au=Rein%2C+Alan&rft.aulast=Rein&rft.aufirst=Alan&rft.date=2003-10-14&rft.volume=100&rft.issue=21&rft.spage=11929&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 - 2003-12-04 N1 - Date created - 2003-10-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1983 Dec;48(3):779-84 [6313971] Proc Natl Acad Sci U S A. 1980 May;77(5):2994-8 [6248878] Proc Natl Acad Sci U S A. 1986 Oct;83(19):7246-50 [3489936] Genes Dev. 1989 Apr;3(4):469-78 [2721960] J Virol. 1994 Apr;68(4):2556-69 [8139035] Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1304-9 [9037048] EMBO J. 1998 Mar 16;17(6):1555-68 [9501077] Science. 1999 Jan 1;283(5398):80-3 [9872746] EMBO J. 1999 Sep 1;18(17):4700-10 [10469649] J Virol. 1983 Dec;48(3):685-96 [6313967] Virology. 2000 Mar 15;268(2):294-307 [10704338] J Virol. 2000 Aug;74(16):7250-60 [10906179] Nature. 2000 Sep 21;407(6802):409-13 [11014200] J Virol. 2001 Oct;75(19):9357-66 [11533199] J Virol. 2002 May;76(10):4679-87 [11967285] J Virol. 2002 Jun;76(11):5667-77 [11991995] Nat Struct Biol. 2002 Jul;9(7):537-43 [12032547] J Virol. 2002 Nov;76(21):10801-10 [12368323] Trends Cell Biol. 2002 Dec;12(12):569-79 [12495845] EMBO J. 2003 Jun 16;22(12):2886-92 [12805204] Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11678-83 [14504385] Curr Top Microbiol Immunol. 1979;86:67-122 [227645] J Virol. 1980 Jan;33(1):183-95 [6245227] Comment On: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11678-83 [14504385] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized, double-blind, placebo controlled study on analgesic effects of botulinum toxin A. AN - 71268707; 14557564 AB - Botulinum toxin type A (BTXA) is used to treat neurologic disorders associated with increased muscle tone. Its use is often associated with pain relief. A possible direct analgesic effect of BTXA on C and Adelta fibers was studied on 16 healthy volunteers receiving 30 U BTXA into one forearm and pure saline into the other. To exclude the secondary effect due to muscular tone reduction, BTXA was injected intradermally. Thermal sensory testing of heat pain (threshold and tolerance) and neuroselective current sensory testing of current pain threshold/tolerance were performed at baseline and 3, 14, and 28 days after treatment. Thereafter, on day 28, capsaicin was administered simultaneously into both forearms to evaluate a possible peripheral effect and central effect on pain processing and on the axon reflex flare. The authors observed no significant difference in any of the perception outcome measures between BTXA and placebo pretreated areas. Flare areas as a result of the release of neuropeptides after capsaicin application showed no differences. The results suggest that pain reduction after BTXA treatment is mediated through its effect on muscle tone rather than a direct analgesic effect. JF - Neurology AU - Voller, B AU - Sycha, T AU - Gustorff, B AU - Schmetterer, L AU - Lehr, S AU - Eichler, H G AU - Auff, E AU - Schnider, P AD - Department of Clinical Pharmacology, University of Vienna, Austria. vollerb@ninds.nih.gov Y1 - 2003/10/14/ PY - 2003 DA - 2003 Oct 14 SP - 940 EP - 944 VL - 61 IS - 7 KW - Analgesics KW - 0 KW - Placebos KW - Botulinum Toxins, Type A KW - EC 3.4.24.69 KW - Capsaicin KW - S07O44R1ZM KW - Abridged Index Medicus KW - Index Medicus KW - Reference Values KW - Double-Blind Method KW - Humans KW - Nerve Fibers, Unmyelinated -- drug effects KW - Electric Stimulation KW - Injections, Intradermal KW - Pain Threshold -- drug effects KW - Adult KW - Treatment Outcome KW - Hot Temperature -- adverse effects KW - Skin -- innervation KW - Pain Measurement -- drug effects KW - Nerve Fibers, Myelinated -- drug effects KW - Female KW - Forearm KW - Hyperalgesia -- chemically induced KW - Male KW - Pain -- prevention & control KW - Pain -- drug therapy KW - Botulinum Toxins, Type A -- adverse effects KW - Botulinum Toxins, Type A -- therapeutic use KW - Pain -- chemically induced KW - Analgesics -- therapeutic use KW - Analgesics -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71268707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=A+randomized%2C+double-blind%2C+placebo+controlled+study+on+analgesic+effects+of+botulinum+toxin+A.&rft.au=Voller%2C+B%3BSycha%2C+T%3BGustorff%2C+B%3BSchmetterer%2C+L%3BLehr%2C+S%3BEichler%2C+H+G%3BAuff%2C+E%3BSchnider%2C+P&rft.aulast=Voller&rft.aufirst=B&rft.date=2003-10-14&rft.volume=61&rft.issue=7&rft.spage=940&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=1526-632X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-19 N1 - Date created - 2003-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Second cancers after radiotherapy: any evidence for radiation-induced genomic instability? AN - 19180899; 5765992 AB - Do second primary cancers in humans arise from radiation-induced somatic genomic instability after radiotherapy for the first malignancy? The amount of truly pertinent human information on this issue is sparse, leading to the conclusion that we cannot confirm or refute that instability induction by radiation is involved. However, the in vitro findings of radiation-induced genomic instability through bystander effects or increased mutation rates in cell progeny of apparently normal but irradiated cells are provocative and their transferability to human in vivo biology deserves further investigation. We describe possible animal and human studies to stimulate ideas, but the collaborative commitment of multiple large institutions to tumor tissue procurement and retrieval will be essential. In addition, detecting the temporal progression of genomic instability and identifying the salient genetic events as being radiation-induced will be pivotal. Execution of some of the studies suggested is not possible now, but applying next-generation methods could bring the concepts to fruition. As nearly one in 10 cancer diagnoses are second (or higher) malignancies, it is important to understand the contribution of radiotherapy to second cancer induction and pursue well-coordinated efforts to determine the role of induced genomic instability. JF - Oncogene AU - Sigurdson, A J AU - Jones, I M AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Boulevard, EPS 7092, MSC 7238, Bethesda, MD 20892-7238, USA, sigurdsa@mail.nih.gov Y1 - 2003/10/13/ PY - 2003 DA - 2003 Oct 13 SP - 7018 EP - 7027 VL - 22 IS - 45 SN - 0950-9232, 0950-9232 KW - man KW - Oncogenes & Growth Factors Abstracts; Toxicology Abstracts; Genetics Abstracts KW - Genotoxicity KW - Radiotherapy KW - Cancer KW - DNA damage KW - Genomic instability KW - Radiation KW - Reviews KW - Side effects KW - X 24210:Radiation & radioactive materials KW - G 07234:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19180899?accountid=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=Oncogene&rft.atitle=Second+cancers+after+radiotherapy%3A+any+evidence+for+radiation-induced+genomic+instability%3F&rft.au=Sigurdson%2C+A+J%3BJones%2C+I+M&rft.aulast=Sigurdson&rft.aufirst=A&rft.date=2003-10-13&rft.volume=22&rft.issue=45&rft.spage=7018&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/10.1038%2Fsj.onc.1206989 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Radiotherapy; Side effects; Radiation; Genomic instability; DNA damage; Genotoxicity; Reviews; Cancer DO - http://dx.doi.org/10.1038/sj.onc.1206989 ER - TY - JOUR T1 - Base excision repair intermediates induce p53-independent cytotoxic and genotoxic responses. AN - 75752072; 12882965 AB - DNA alkylation damage is primarily repaired by the base excision repair (BER) machinery in mammalian cells. In repair of the N-alkylated purine base lesion, for example, alkyl adenine DNA glycosylase (Aag) recognizes and removes the base, and DNA polymerase beta (beta-pol) contributes the gap tailoring and DNA synthesis steps. It is the loss of beta-pol-mediated 5'-deoxyribose phosphate removal that renders mouse fibroblasts alkylation-hypersensitive. Here we report that the hypersensitivity of beta-pol-deficient cells after methyl methanesulfonate-induced alkylation damage is wholly dependent upon glycosylase-mediated initiation of repair, indicating that alkylated base lesions themselves are tolerated in these cells and demonstrate that beta-pol protects against accumulation of toxic BER intermediates. Further, we find that these intermediates are initially tolerated in vivo by a second repair pathway, homologous recombination, inducing an increase in sister chromatid exchange events. If left unresolved, these BER intermediates trigger a rapid block in DNA synthesis and cytotoxicity. Surprisingly, both the cytotoxic and genotoxic signals are independent of both the p53 response and mismatch DNA repair pathways, demonstrating that p53 is not required for a functional BER pathway, that the observed damage response is not part of the p53 response network, and that the BER intermediate-induced cytotoxic and genotoxic effects are distinct from the mechanism engaged in response to mismatch repair signaling. These studies demonstrate that, although base damage is repaired by the BER pathway, incomplete BER intermediates are shuttled into the homologous recombination pathway, suggesting possible coordination between BER and the recombination machinery. JF - The Journal of biological chemistry AU - Sobol, Robert W AU - Kartalou, Maria AU - Almeida, Karen H AU - Joyce, Donna F AU - Engelward, Bevin P AU - Horton, Julie K AU - Prasad, Rajendra AU - Samson, Leona D AU - Wilson, Samuel H AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/10/10/ PY - 2003 DA - 2003 Oct 10 SP - 39951 EP - 39959 VL - 278 IS - 41 SN - 0021-9258, 0021-9258 KW - Alkylating Agents KW - 0 KW - Tumor Suppressor Protein p53 KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - DNA KW - 9007-49-2 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - DNA Polymerase beta KW - EC 2.7.7.- KW - 3-methyladenine-DNA glycosylase KW - EC 3.2.2.- KW - DNA Glycosylases KW - Index Medicus KW - Animals KW - DNA Polymerase beta -- deficiency KW - Methylnitronitrosoguanidine -- toxicity KW - DNA Polymerase beta -- genetics KW - DNA Glycosylases -- deficiency KW - DNA -- metabolism KW - Mice KW - Tumor Suppressor Protein p53 -- metabolism KW - DNA -- biosynthesis KW - DNA Polymerase beta -- metabolism KW - Mice, Knockout KW - Phenotype KW - Methyl Methanesulfonate -- toxicity KW - Base Sequence KW - DNA Methylation KW - Cells, Cultured KW - DNA Glycosylases -- metabolism KW - Recombination, Genetic KW - DNA -- genetics KW - DNA Glycosylases -- genetics KW - DNA -- chemistry KW - Alkylating Agents -- toxicity KW - Mutation KW - DNA Repair -- genetics KW - DNA Repair -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75752072?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Base+excision+repair+intermediates+induce+p53-independent+cytotoxic+and+genotoxic+responses.&rft.au=Sobol%2C+Robert+W%3BKartalou%2C+Maria%3BAlmeida%2C+Karen+H%3BJoyce%2C+Donna+F%3BEngelward%2C+Bevin+P%3BHorton%2C+Julie+K%3BPrasad%2C+Rajendra%3BSamson%2C+Leona+D%3BWilson%2C+Samuel+H&rft.aulast=Sobol&rft.aufirst=Robert&rft.date=2003-10-10&rft.volume=278&rft.issue=41&rft.spage=39951&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 - 2003-12-02 N1 - Date created - 2003-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel small molecule inhibitors of botulinum neurotoxin A metalloprotease activity. AN - 75704543; 14511652 AB - Botulinum neurotoxins (BoNTs) are among the most lethal biological substances to have been weaponized and are listed as biodefense category A agents. Currently, no small molecule (non-peptidic) therapeutics exist to counter this threat; hence, identifying and developing compounds that inhibit BoNTs is a high priority. In the present study, a high-throughput assay was used to identify small molecules that inhibit the metalloprotease activity of BoNT serotype A light chain (BoNT/A LC). All inhibitors were further verified using a HPLC-based assay. Conformational analyses of these compounds, in conjunction with molecular docking studies, were used to predict structural features that contribute to inhibitor binding and potency. Based on these results, a common pharmacophore for BoNT/A LC inhibitors is proposed. This is the first study to report small molecules (non-peptidics) that inhibit BoNT/A LC metalloprotease activity in the low microM range. JF - Biochemical and biophysical research communications AU - Burnett, James C AU - Schmidt, James J AU - Stafford, Robert G AU - Panchal, Rekha G AU - Nguyen, Tam L AU - Hermone, Ann R AU - Vennerstrom, Jonathan L AU - McGrath, Connor F AU - Lane, Douglas J AU - Sausville, Edward A AU - Zaharevitz, Daniel W AU - Gussio, Rick AU - Bavari, Sina AD - Developmental Therapeutics Program, NCI Frederick, Frederick, MD 21702, USA. Y1 - 2003/10/10/ PY - 2003 DA - 2003 Oct 10 SP - 84 EP - 93 VL - 310 IS - 1 SN - 0006-291X, 0006-291X KW - Protease Inhibitors KW - 0 KW - Metalloproteases KW - EC 3.4.- KW - Botulinum Toxins KW - EC 3.4.24.69 KW - Index Medicus KW - Protease Inhibitors -- pharmacology KW - Metalloproteases -- antagonists & inhibitors KW - Botulinum Toxins -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75704543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Novel+small+molecule+inhibitors+of+botulinum+neurotoxin+A+metalloprotease+activity.&rft.au=Burnett%2C+James+C%3BSchmidt%2C+James+J%3BStafford%2C+Robert+G%3BPanchal%2C+Rekha+G%3BNguyen%2C+Tam+L%3BHermone%2C+Ann+R%3BVennerstrom%2C+Jonathan+L%3BMcGrath%2C+Connor+F%3BLane%2C+Douglas+J%3BSausville%2C+Edward+A%3BZaharevitz%2C+Daniel+W%3BGussio%2C+Rick%3BBavari%2C+Sina&rft.aulast=Burnett&rft.aufirst=James&rft.date=2003-10-10&rft.volume=310&rft.issue=1&rft.spage=84&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 - 2003-12-02 N1 - Date created - 2003-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Protein Contortionist: Core Mutations of GB1 that Induce Dimerization and Domain Swapping AN - 19813646; 5754344 AB - Immunoglobulin-binding domain B1 of streptococcal protein G (GB1), a small (56 residues), stable, single-domain protein, is one of the most extensively used model systems in the area of protein folding and design. Recently, NMR and X-ray structures of a quintuple GB1 core mutant (L5V/A26F/F30V/Y33F/A34F) that showed an unexpected, intertwined tetrameric architecture were determined. Here, we report the NMR structure of another mutant, derived from the tetramer by reverting the single amino acid position F26 back to the wild-type sequence A26. The structure reveals a domain-swapped dimer that involves exchange of the second beta -hairpin. The resulting overall structure comprises an eight-stranded beta -sheet whose concave side is covered by two alpha helices. The dimer dissociates into a partially folded, monomeric species with a dissociation constant of 93( plus or minus 10) mu M. JF - Journal of Molecular Biology AU - Byeon, IL AU - Louis, J M AU - Gronenborn, A M AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 130, Bethesda, MD 20892, USA, gronenborn@nih.gov Y1 - 2003/10/10/ PY - 2003 DA - 2003 Oct 10 SP - 141 EP - 152 VL - 333 IS - 1 SN - 0022-2836, 0022-2836 KW - Microbiology Abstracts B: Bacteriology KW - Streptococcus KW - Protein folding KW - Ionizing radiation KW - streptococcal protein G KW - N.M.R. KW - Mutation KW - Amino acid sequence KW - J 02310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19813646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=A+Protein+Contortionist%3A+Core+Mutations+of+GB1+that+Induce+Dimerization+and+Domain+Swapping&rft.au=Byeon%2C+IL%3BLouis%2C+J+M%3BGronenborn%2C+A+M&rft.aulast=Byeon&rft.aufirst=IL&rft.date=2003-10-10&rft.volume=333&rft.issue=1&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1016%2FS0022-2836%2803%2900928-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Protein folding; streptococcal protein G; Ionizing radiation; N.M.R.; Mutation; Amino acid sequence; Streptococcus DO - http://dx.doi.org/10.1016/S0022-2836(03)00928-8 ER - TY - JOUR T1 - Filling a gap in the central metabolism of archaea: prediction of a novel aconitase by comparative-genomic analysis AN - 18899781; 5770731 AB - Aconitase, an essential enzyme of the tricarboxylic acid cycle (TCA), so far has been identified only in a minority of archaeal genomes. This enzyme belongs to the aconitase A family, which is represented in most bacteria and eukaryotes. Using iterative sequence database search, we linked two previously uncharacterized protein families (COG1679 and COG1786), respectively, to the three Fe-S-cluster-associated aconitase domains and the swiveling domain, the four domains that are present in all known aconitase families. The respective genes are often found in one predicted operon and, moreover, are fused in several species, suggesting a functional and physical interaction. We predict that these proteins together comprise a previously undetected, distinct aconitase family, which we designated aconitase X. Aconitase X is encoded in the genomes of many archaea and some proteobacteria. Among archaea, the pattern of aconitase X occurrence complements that of aconitase A such that together the two enzymes account for aconitase activity in all archaea. Phylogenetic analysis indicates that aconitase X is likely to be the ancestral archaeal form, with non-orthologous displacement in some of the archaea apparently brought about by horizontal transfer of the gene for bacterial aconitase A. The prediction of aconitase X completes the TCA cycle for Methanothermobacter thermoautotrophicus and Archaeoglobus fulgidus and suggests that most archaea have a full TCA cycle. JF - FEMS Microbiology Letters 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, makarova@ncbi.nlm.nih.gov Y1 - 2003/10/10/ PY - 2003 DA - 2003 Oct 10 SP - 17 EP - 23 PB - Federation of European Microbiological Societies VL - 227 IS - 1 SN - 0378-1097, 0378-1097 KW - genomics KW - protein families KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - G 07320:Bacterial genetics KW - J 02722:Biodegradation, growth, nutrition and leaching KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18899781?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=Filling+a+gap+in+the+central+metabolism+of+archaea%3A+prediction+of+a+novel+aconitase+by+comparative-genomic+analysis&rft.au=Makarova%2C+K+S%3BKoonin%2C+E+V&rft.aulast=Makarova&rft.aufirst=K&rft.date=2003-10-10&rft.volume=227&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/10.1016%2FS0378-1097%2803%2900596-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0378-1097(03)00596-2 ER - TY - JOUR T1 - Kinetics of Transcription Initiation at lacP1: Multiple roles of cyclic AMP receptor protein AN - 18877375; 5730296 AB - The cyclic AMP receptor protein (CRP) acts as a transcription activator at many promoters of Escherichia coli. We have examined the kinetics of open complex formation at the lacP1 promoter using tryptophan fluorescence of RNA polymerase and DNA fragments with 2-aminopurine substituted at specific positions. Apart from the closed complex formation and promoter clearance, we were able to detect three steps. The first step after the closed complex formation leads to a rapid increase of 2-aminopurine fluorescence. This was followed by another rapid step in which quenching of tryptophan fluorescence of RNA polymerase was observed. The slowest step detected by 2-aminopurine fluorescence increase is assigned to the final open complex formation. We have found that CRP not only enhances RNA polymerase binding at the promoter, but also enhances the slowest isomerization step by about 2-fold. Furthermore, potassium permanganate probing shows that the conformation of the open complex in the presence of CRP appears qualitatively and quantitatively different from that in the absence of CRP, suggesting that contact with RNA polymerase is maintained throughout the transcription initiation. JF - Journal of Biological Chemistry AU - Liu, M AU - Gupte, G AU - Roy, S AU - Bandwar, R P AU - Patel, S S AU - Garges, S AD - Laboratory of Molecular Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892-4264, the Department of Biophysics, Bose Institute, P-1/12, C.I.T. Scheme VII M, Calcutta 700 054, India, liumo@pop.nci.nih.gov Y1 - 2003/10/10/ PY - 2003 DA - 2003 Oct 10 SP - 39755 EP - 39761 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 278 IS - 41 SN - 0021-9258, 0021-9258 KW - 2-Aminopurine KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02726:RNA and ribosomes KW - N 14553:Transcription initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18877375?accountid=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=Kinetics+of+Transcription+Initiation+at+lacP1%3A+Multiple+roles+of+cyclic+AMP+receptor+protein&rft.au=Liu%2C+M%3BGupte%2C+G%3BRoy%2C+S%3BBandwar%2C+R+P%3BPatel%2C+S+S%3BGarges%2C+S&rft.aulast=Liu&rft.aufirst=M&rft.date=2003-10-10&rft.volume=278&rft.issue=41&rft.spage=39755&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M305995200 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1074/jbc.M305995200 ER - TY - JOUR T1 - Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions. AN - 73669845; 13679147 AB - DNA topoisomerase I (Top1) is converted into a cellular poison by camptothecin (CPT) and various endogenous and exogenous DNA lesions. In this study, we used X-ray repair complementation group 1 (XRCC1)-deficient and XRCC1-complemented EM9 cells to investigate the mechanism by which XRCC1 affects the cellular responses to Top1 cleavage complexes induced by CPT. XRCC1 complementation enhanced survival to CPT-induced DNA lesions produced independently of DNA replication. CPT-induced comparable levels of Top1 cleavage complexes (single-strand break (SSB) and DNA-protein cross-links (DPC)) in both XRCC1-deficient and XRCC1-complemented cells. However, XRCC1-complemented cells repaired Top1-induced DNA breaks faster than XRCC1-deficient cells, and exhibited enhanced tyrosyl DNA phosphodiesterase (Tdp1) and polynucleotide kinase phosphatase (PNKP) activities. XRCC1 immunoprecipitates contained Tdp1 polypeptide, and both Tdp1 and PNKP activities, indicating a functional connection between the XRCC1 single-strand break repair pathway and the repair of Top1 covalent complexes by Tdp1 and PNKP. JF - DNA repair AU - Plo, Isabelle AU - Liao, Zhi Yong AU - Barceló, Juana M AU - Kohlhagen, Glenda AU - Caldecott, Keith W AU - Weinfeld, Michael AU - Pommier, Yves AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institute of Health, Building 37, Room 5068, Bethesda, MD, USA. Y1 - 2003/10/07/ PY - 2003 DA - 2003 Oct 07 SP - 1087 EP - 1100 VL - 2 IS - 10 SN - 1568-7864, 1568-7864 KW - DNA, Single-Stranded KW - 0 KW - DNA-Binding Proteins KW - X-ray repair cross complementing protein 1 KW - Polynucleotide 5'-Hydroxyl-Kinase KW - EC 2.7.1.78 KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - tyrosyl-DNA phosphodiesterase KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Animals KW - DNA, Single-Stranded -- genetics KW - Cell Survival -- drug effects KW - Camptothecin -- pharmacology KW - Genetic Complementation Test KW - CHO Cells KW - Polynucleotide 5'-Hydroxyl-Kinase -- metabolism KW - Molecular Conformation KW - DNA Damage -- genetics KW - DNA Replication KW - Cricetinae KW - DNA Repair -- physiology KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- physiology KW - Phosphoric Diester Hydrolases -- metabolism KW - DNA Topoisomerases, Type I -- metabolism KW - Phosphoric Diester Hydrolases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73669845?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+repair&rft.atitle=Association+of+XRCC1+and+tyrosyl+DNA+phosphodiesterase+%28Tdp1%29+for+the+repair+of+topoisomerase+I-mediated+DNA+lesions.&rft.au=Plo%2C+Isabelle%3BLiao%2C+Zhi+Yong%3BBarcel%C3%B3%2C+Juana+M%3BKohlhagen%2C+Glenda%3BCaldecott%2C+Keith+W%3BWeinfeld%2C+Michael%3BPommier%2C+Yves&rft.aulast=Plo&rft.aufirst=Isabelle&rft.date=2003-10-07&rft.volume=2&rft.issue=10&rft.spage=1087&rft.isbn=&rft.btitle=&rft.title=DNA+repair&rft.issn=15687864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-04 N1 - Date created - 2003-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Uncoupling cell shrinkage from apoptosis reveals that Na+ influx is required for volume loss during programmed cell death. AN - 75719584; 12821680 AB - Cell shrinkage, or the loss of cell volume, is a ubiquitous characteristic of programmed cell death that is observed in all examples of apoptosis, independent of the death stimulus. This decrease in cell volume occurs in synchrony with other classical features of apoptosis. The molecular basis for cell shrinkage during apoptosis involves fluxes of intracellular ions including K+, Na+, and Cl-. Here we show for the first time that these ion fluxes, but not cell shrinkage, are necessary for apoptosis. Using sodium-substituted medium during anti-Fas treatment of Jurkat cells, we observed cellular swelling, a property normally associated with necrosis, in contrast to the typical cell shrinkage. Surprisingly, these swollen cells displayed all of the other classical features of apoptosis, including chromatin condensation, externalization of phosphatidylserine, caspase activity, poly(ADP)-ribose polymerase cleavage, and internucleosomal DNA degradation. These swollen cells had a marked decrease in intracellular potassium, and subsequent inhibition of this potassium loss completely blocked apoptosis. Reintroduction of sodium ions in cell cultures reversed this cellular swelling, resulting in a dramatic loss of cell volume and the characteristic apoptotic morphology. Additionally, inhibition of sodium influx using a sodium channel blocker saxitoxin completely prevented the onset of anti-Fas-induced apoptosis in Jurkat cells. These findings suggest that sodium influx can control not only changes in cell size but also the activation of apoptosis, whereas potassium ion loss controls the progression of the cell death process. Therefore cell shrinkage can be separated from other features of apoptosis. JF - The Journal of biological chemistry AU - Bortner, Carl D AU - Cidlowski, John A AD - Laboratory of Signal Transduction, NIEHS, Department of Health and Human Services, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/10/03/ PY - 2003 DA - 2003 Oct 03 SP - 39176 EP - 39184 VL - 278 IS - 40 SN - 0021-9258, 0021-9258 KW - Chromatin KW - 0 KW - Ions KW - Nucleosomes KW - Phosphatidylserines KW - Chlorine KW - 4R7X1O2820 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - DNA KW - 9007-49-2 KW - Sodium KW - 9NEZ333N27 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Caspases KW - EC 3.4.22.- KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Microscopy, Confocal KW - Potassium -- chemistry KW - Caspases -- chemistry KW - Chromatin -- metabolism KW - Poly(ADP-ribose) Polymerases -- chemistry KW - DNA -- metabolism KW - Humans KW - Nucleosomes -- metabolism KW - Jurkat Cells KW - Microscopy, Fluorescence KW - Phosphatidylserines -- chemistry KW - Necrosis KW - Adenosine Triphosphate -- metabolism KW - Electrophoresis, Agar Gel KW - Flow Cytometry KW - Chlorine -- chemistry KW - Lipid Metabolism KW - Apoptosis KW - Sodium -- chemistry KW - Sodium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75719584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Uncoupling+cell+shrinkage+from+apoptosis+reveals+that+Na%2B+influx+is+required+for+volume+loss+during+programmed+cell+death.&rft.au=Bortner%2C+Carl+D%3BCidlowski%2C+John+A&rft.aulast=Bortner&rft.aufirst=Carl&rft.date=2003-10-03&rft.volume=278&rft.issue=40&rft.spage=39176&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 - 2003-11-06 N1 - Date created - 2003-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine transporter: basic science and human variation of a key molecule for dopaminergic function, locomotion, and parkinsonism. AN - 85378959; pmid-14531049 AB - We review the basic science of the dopamine transporter (DAT), a key neurotransmitter for locomotor control and reward systems, including those lost or deranged in Parkinson's disease (PD). Physiology, pharmaceutical features, expression, cDNA, protein structure/function relationships, and phosphorylation and regulation are discussed. The localization of DAT provides the best marker for the integrity of just the pre-synaptic dopaminergic systems that are most affected in PD. Its function is key for the actions of several toxins that provide some of the best current models for idiopathic parkinsonism, and its variation can clearly alter movement. The wealth of information about this interesting molecule that has been developed over the last 12 years has led to increased interest in DAT among workers interested in both normal and abnormal movement.Copyright 2003 Movement Disorder Society JF - Movement disorders : official journal of the Movement Disorder Society AU - Uhl, George R AD - Molecular Neurobiology Branch, NIDA-IRP, National Institutes of Health, Bethesda, Maryland, USA. guhl@intra.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - S71 EP - S80 VL - 18 Suppl 7 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Corpus Striatum: physiopathology KW - DNA-Binding Proteins: genetics KW - *Dopamine: physiology KW - Dopamine Plasma Membrane Transport Proteins KW - Gene Expression: physiology KW - Humans KW - Linkage Disequilibrium: genetics KW - *Locomotion: physiology KW - *Membrane Glycoproteins KW - Membrane Transport Proteins: genetics KW - *Membrane Transport Proteins: physiology KW - Mice KW - Mice, Knockout KW - *Nerve Tissue Proteins KW - Neural Pathways: physiopathology KW - Parkinson Disease: genetics KW - *Parkinson Disease: physiopathology KW - Parkinsonian Disorders: genetics KW - Parkinsonian Disorders: physiopathology KW - Polymorphism, Single Nucleotide: genetics KW - *Saccharomyces cerevisiae Proteins KW - Substantia Nigra: physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85378959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Dopamine+transporter%3A+basic+science+and+human+variation+of+a+key+molecule+for+dopaminergic+function%2C+locomotion%2C+and+parkinsonism.&rft.au=Uhl%2C+George+R&rft.aulast=Uhl&rft.aufirst=George&rft.date=2003-10-01&rft.volume=18+Suppl+7&rft.issue=&rft.spage=S71&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - EEG effects of conventional and denicotinized cigarettes in a spaced smoking paradigm. AN - 85378328; pmid-14572505 AB - Although there is a documented association between plasma nicotine levels and smoking behavior, recent studies indicate that denicotinized cigarettes reduced craving and symptoms of tobacco withdrawal. Denicotinized cigarettes (that deliver tar but insignificant amounts of nicotine) and conventional cigarettes were compared in a within-subject spaced smoking study. In six sessions, subjects (n=10) smoked denicotinized cigarettes or conventional cigarettes every 30, 60 or 240 min (8, 4 or 1 cigarette(s)). EEG effects of the last cigarette of each session were deduced by comparisons with EEG recordings collected before smoking. Conventional cigarettes increased spectral edge EEG frequency, decreased theta power and increased beta1 power. Denicotinized cigarettes decreased spectral frequency. The EEG effects of both cigarettes depended upon the recentness of smoking. The results indicate that nicotine delivery, recentness and the process of smoking importantly influence the EEG; other, non-nicotine components of tobacco smoke may also exert EEG effects. JF - Brain and cognition AU - Pickworth, Wallace B AU - O'Hare, Elizabeth D AU - Fant, Reginald V AU - Moolchan, Eric T AD - NIDA, Intramural Research Program, 5500 Nathan Shock Drive, P.O. Box 5180, Baltimore, MD 21224, USA. wpickwo@intra.nida.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 75 EP - 81 VL - 53 IS - 1 SN - 0278-2626, 0278-2626 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - *Electroencephalography: drug effects KW - Female KW - Humans KW - Male KW - Middle Aged KW - Nicotine: administration & dosage KW - Nicotine: blood KW - *Nicotine: pharmacology KW - *Periodicity KW - *Smoking UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85378328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+and+cognition&rft.atitle=EEG+effects+of+conventional+and+denicotinized+cigarettes+in+a+spaced+smoking+paradigm.&rft.au=Pickworth%2C+Wallace+B%3BO%27Hare%2C+Elizabeth+D%3BFant%2C+Reginald+V%3BMoolchan%2C+Eric+T&rft.aulast=Pickworth&rft.aufirst=Wallace&rft.date=2003-10-01&rft.volume=53&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Brain+and+cognition&rft.issn=02782626&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Thyroarytenoid muscle responses to air pressure stimulation of the laryngeal mucosa in humans. AN - 85364956; pmid-14587972 AB - Others have observed glottic adduction in response to air puff stimuli and suggested that this is a reliable indicator of laryngeal sensation. We undertook to determine whether the same thresholds are found if one uses either thyroarytenoid (TA) muscle responses or subjects' reports of laryngeal sensation. We also studied the characteristics of TA responses to unilateral air pressure stimulation of the mucosa overlying the arytenoid cartilages. Ten normal volunteers provided button press responses to air pressure stimuli during bilateral TA electromyography. Similar thresholds were determined by reports of sensation as by electromyographic responses (p < .0005). The early TA responses occurred either around 80 ms or around 125 ms after onset of the air puff, with equal frequency on the ipsilateral and contralateral sides. The TA muscle responses to air pressure stimulation differ in physiological characteristics from the laryngeal adductor reflex that occurs in response to electrical stimulation of the superior laryngeal nerve. JF - The Annals of otology, rhinology, and laryngology AU - Bhabu, Priyanka AU - Poletto, Christopher AU - Mann, Eric AU - Bielamowicz, Steven AU - Ludlow, Christy L AD - Laryngeal and Speech Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 834 EP - 840 VL - 112 IS - 10 SN - 0003-4894, 0003-4894 KW - National Library of Medicine KW - Adult KW - Aged KW - *Air Pressure KW - Electromyography KW - Female KW - Humans KW - *Laryngeal Muscles: physiology KW - *Larynx KW - Male KW - Middle Aged KW - Physical Stimulation KW - Reaction Time KW - Reference Values KW - *Respiratory Mucosa: physiology KW - Sensory Thresholds UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85364956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.atitle=Thyroarytenoid+muscle+responses+to+air+pressure+stimulation+of+the+laryngeal+mucosa+in+humans.&rft.au=Bhabu%2C+Priyanka%3BPoletto%2C+Christopher%3BMann%2C+Eric%3BBielamowicz%2C+Steven%3BLudlow%2C+Christy+L&rft.aulast=Bhabu&rft.aufirst=Priyanka&rft.date=2003-10-01&rft.volume=112&rft.issue=10&rft.spage=834&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.issn=00034894&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Expression of prestin, a membrane motor protein, in the mammalian auditory and vestibular periphery. AN - 85362929; pmid-14553901 AB - Hair cells are specialized mechanoreceptors common to auditory and vestibular sensory organs of mammalian and non-mammalian species. Different hair cells are believed to share common features related to their mechanosensory function. It has been shown that hair cells possess various forms of motile properties that enhance their receptor function. Membrane-based electromotility is a form of hair cell motility observed in isolated outer hair cells (OHCs) of the cochlea. A novel membrane protein, prestin, recently cloned from gerbil and rat tissues, is presumably responsible for electromotility. We cloned prestin from mouse organ of Corti and confirmed strong homology of this protein among different rodent species. We explored whether or not prestin is present in hair cells of the vestibular system. Using reverse transcription-polymerase chain reaction, we demonstrated that prestin is expressed in mouse and rat auditory and vestibular organs, but not in chicken auditory periphery. In situ hybridization and immunolocalization studies confirmed the presence of prestin in OHCs as well as in vestibular hair cells (VHCs) of rodent saccule, utricle and crista ampullaris. However, in the VHCs, staining of varying intensity with anti-prestin antibodies was observed in the cytoplasm, but not in the lateral plasma membrane or in the stereociliary membrane. Whole-cell patch-clamp recordings showed that VHCs do not possess the voltage-dependent capacitance associated with membrane-based electromotility. We conclude that although prestin is expressed in VHCs, it is unlikely that it supports the form of somatic motility observed in OHCs. JF - Hearing research AU - Adler, Henry J AU - Belyantseva, Inna A AU - Merritt, Raymond C AU - Frolenkov, Gregory I AU - Dougherty, Gerard W AU - Kachar, Bechara AD - Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bldg. 50, Room 4249, Bethesda, MD 20892-8027, USA. adlerh@nidcd.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 27 EP - 40 VL - 184 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Index Medicus KW - National Library of Medicine KW - Amino Acid Sequence KW - Animals KW - Anion Transport Proteins KW - *Auditory Pathways: metabolism KW - Cell Movement: physiology KW - Chickens KW - Cloning, Molecular KW - Electric Capacitance KW - Electrophysiology KW - Hair Cells, Auditory: physiology KW - Hair Cells, Auditory, Outer: physiology KW - *Mice: metabolism KW - Molecular Motor Proteins KW - Molecular Sequence Data KW - Organ of Corti: metabolism KW - Proteins: genetics KW - *Proteins: metabolism KW - *Rats: metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - Sequence Homology, Amino Acid KW - *Vestibule, Labyrinth: metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85362929?accountid=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=Expression+of+prestin%2C+a+membrane+motor+protein%2C+in+the+mammalian+auditory+and+vestibular+periphery.&rft.au=Adler%2C+Henry+J%3BBelyantseva%2C+Inna+A%3BMerritt%2C+Raymond+C%3BFrolenkov%2C+Gregory+I%3BDougherty%2C+Gerard+W%3BKachar%2C+Bechara&rft.aulast=Adler&rft.aufirst=Henry&rft.date=2003-10-01&rft.volume=184&rft.issue=1-2&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Hearing+research&rft.issn=03785955&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Planar and vertical signals control cellular differentiation and patterning in the mammalian cochlea. AN - 85295701; pmid-14561877 AB - The sensory epithelium of the mammalian cochlea is composed of a regular mosaic of sensory hair cells and nonsensory supporting cells. During development, differentiation occurs in a gradient that progresses along the axis of the cochlea from base to apex. To begin to identify some of the factors that regulate this developmental process, the potential roles of planar and vertical signals were examined during early stages of cochlear development. We demonstrate roles for both underlying mesenchymal cells and adjacent epithelial cells in the differentiation and patterning of the sensory epithelium, and in particular in the development of mechanosensory hair cells. As development proceeds, the requirements for both planar and vertical signals decrease, and development of the sensory epithelium becomes essentially independent from these cues. Finally, we demonstrate that the temporal gradient of cellular differentiation is not dependent on planar signals within the developing sensory epithelium. JF - The Journal of Neuroscience AU - Montcouquiol Mireille AU - Kelley, Matthew W AD - Section on Developmental Neuroscience, National Institute on Deafness and Other Communication Disorders-National Institutes of Health, Rockville, Maryland 20850, USA.; Department of Cell Biology, School of Medicine, Georgetown University Medical Center, Georgetown University PY - 2003 SP - 9469 EP - 9478 VL - 23 IS - 28 SN - 0270-6474, 0270-6474 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85295701?accountid=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=Planar+and+vertical+signals+control+cellular+differentiation+and+patterning+in+the+mammalian+cochlea.&rft.au=Montcouquiol+Mireille%3BKelley%2C+Matthew+W&rft.aulast=Montcouquiol+Mireille&rft.aufirst=&rft.date=2003-10-01&rft.volume=23&rft.issue=28&rft.spage=9469&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 - Cell cycle activation in lung adenocarcinoma cells by the ErbB3/phosphatidylinositol 3-kinase/Akt pathway. AN - 75776386; 12896906 AB - Although ErbB3, a member of the epidermal growth factor receptor family, has been implicated in mammary tumorigenesis, investigation of its role in lung tumorigenesis has been limited. We found that ErbB3 was present at high levels in five of seven human lung adenocarcinoma cell lines examined, along with its ligands, heregulins alpha and beta, whereas ErbB3 was absent from HPL1D, a non- transformed cell line from human pulmonary peripheral epithelium. Interactions and effects of ErbB3 were studied in detail in adenocarcinoma lines H441 and H1373. Complexes containing phosphorylated ErbB2, phosphorylated ErbB3 and the p85 regulatory subunit of phosphoinositidyl 3-kinase were detected by co-immunoprecipitation experiments and were present constitutively even in the absence of serum-stimulated cell division. Serum treatment increased the pErbB3/p85 complexes and also stimulated phosphorylation of Akt and GSK3beta, increase in cyclin D1 and cell cycle progression, and these events were blocked by the Akt activation inhibitor LY294002. An ErbB3-specific antisense oligonucleotide reduced amounts of ErbB3 protein and p85 complex in both cell lines, and significantly suppressed cell proliferation. These results together suggest involvement of ErbB3 in growth of lung adenocarcinomas, through activation of phosphoinositidyl 3 kinase and Akt, inactivation of GSK3beta and stabilization of cyclin D1 for cell cycle maintenance. It could be a useful therapeutic target. JF - Carcinogenesis AU - Sithanandam, Gunamani AU - Smith, George T AU - Masuda, Akira AU - Takahashi, Takashi AU - Anderson, Lucy M AU - Fornwald, Laura W AD - Basic Research Program, SAIC Frederick, National Cancer Institute at Frederick, Building 538, Ft. Detrick, Frederick, MD 21702-1201, USA. sithanan@mail.ncifcrf.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 1581 EP - 1592 VL - 24 IS - 10 SN - 0143-3334, 0143-3334 KW - Neuregulin-1 KW - 0 KW - Proto-Oncogene Proteins KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Receptor, ErbB-3 KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Glycogen Synthase Kinase 3 KW - EC 2.7.11.26 KW - Index Medicus KW - Neuregulin-1 -- metabolism KW - Immunoblotting KW - Tumor Cells, Cultured KW - Phosphorylation KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Receptor, ErbB-2 -- metabolism KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Glycogen Synthase Kinase 3 -- metabolism KW - Flow Cytometry KW - Precipitin Tests KW - Adenocarcinoma -- metabolism KW - Receptor, ErbB-3 -- metabolism KW - Cell Cycle -- physiology KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75776386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cell+cycle+activation+in+lung+adenocarcinoma+cells+by+the+ErbB3%2Fphosphatidylinositol+3-kinase%2FAkt+pathway.&rft.au=Sithanandam%2C+Gunamani%3BSmith%2C+George+T%3BMasuda%2C+Akira%3BTakahashi%2C+Takashi%3BAnderson%2C+Lucy+M%3BFornwald%2C+Laura+W&rft.aulast=Sithanandam&rft.aufirst=Gunamani&rft.date=2003-10-01&rft.volume=24&rft.issue=10&rft.spage=1581&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-28 N1 - Date created - 2003-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I study of 9-aminocamptothecin as a colloidal dispersion formulation given as a fortnightly 72-h infusion. AN - 75765953; 12819941 AB - A phase I pharmacologic study was undertaken to determine the maximum tolerated dose (MTD), to characterize the pharmacokinetic profile, and to evaluate all toxicities of the aqueous colloidal dispersion formulation of 9-aminocampothecin (9-AC). 9-AC was administered as a constant 72-h i.v. infusion every 2 weeks to adult cancer patients at dose rates ranging from 25 to 59 microg/m2 per hour. Twenty patients with refractory solid tumors received a total of 86 courses of 9-AC at four dose levels. Myelosuppression, particularly granulocytopenia, was the most common toxicity. Two of six assessable patients entered at 59 microg/m2 per hour had dose-limiting toxicity (grade 3 diarrhea or need for a 2-week treatment delay to permit granulocyte recovery), whereas lower doses were well tolerated. At the recommended dose, 47 microg/m2 per hour, the average steady-state plasma levels (Cpss) and area under the curve (AUC) of 9-AC lactone and total drug were 15 and 75 nM, and 1034 and 4220 nM.h, respectively. A moderate correlation was seen between 9-AC lactone AUC and the percentage decrease in granulocytes. The recommended phase II dose of 9-AC colloidal dispersion as a 72-h infusion every 14 days is 47 microg/m2 per hour (1.13 mg/m2 per day). The Cpss of 9-AC lactone at this dose exceeded the 10 nM threshold level for preclinical activity. JF - Cancer chemotherapy and pharmacology AU - Leguizamo, Jorge AU - Quinn, Mary AU - Takimoto, Chris H AU - Liang, Michael D AU - Ismail, Abdel-Salam Attia AU - Pang, Janet AU - Dahut, William AU - Grem, Jean L AD - National Cancer Institute-Navy Medical Oncology, Cancer Therapeutics Branch, Center for Cancer Research, National Naval Medical Center, Bethesda, Maryland, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 333 EP - 338 VL - 52 IS - 4 SN - 0344-5704, 0344-5704 KW - Acetamides KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Colloids KW - Excipients KW - 9-aminocamptothecin KW - 5MB77ICE2Q KW - dimethylacetamide KW - JCV5VDB3HY KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Area Under Curve KW - Humans KW - Aged KW - Drug Resistance, Neoplasm KW - Agranulocytosis -- chemically induced KW - Blood Cell Count KW - Adult KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Agranulocytosis -- blood KW - Neoplasms -- drug therapy KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Camptothecin -- analogs & derivatives KW - Camptothecin -- therapeutic use KW - Camptothecin -- adverse effects KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Camptothecin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75765953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=A+phase+I+study+of+9-aminocamptothecin+as+a+colloidal+dispersion+formulation+given+as+a+fortnightly+72-h+infusion.&rft.au=Leguizamo%2C+Jorge%3BQuinn%2C+Mary%3BTakimoto%2C+Chris+H%3BLiang%2C+Michael+D%3BIsmail%2C+Abdel-Salam+Attia%3BPang%2C+Janet%3BDahut%2C+William%3BGrem%2C+Jean+L&rft.aulast=Leguizamo&rft.aufirst=Jorge&rft.date=2003-10-01&rft.volume=52&rft.issue=4&rft.spage=333&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-01 N1 - Date created - 2003-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicogenomic effects of marine brevetoxins in liver and brain of mouse. AN - 75750697; 14529743 AB - Although the polyether brevetoxins (PbTx's) produced by Karenia brevis (the organism responsible for blooms of the Florida red tide) are known to exert their acute toxic effects through ion-channel mediated pathways in neural tissue, prior studies have also demonstrated that at least one form of the toxin (PbTx-6) is bound avidly by the aryl hydrocarbon receptor (AhR). Since AhR binding of a prototypical ligand such as dioxin is the first step in a cascade pathway producing major changes in gene expression, we reasoned that PbTx-6 might produce similar genomic-wide changes in expression. Mice were injected i.p. with sub-lethal doses of PbTx's (either 1.5 or 3 mg/g body weight of PbTx-6; or 0.15 mg/g body weight of PbTx-2, a toxin not avidly bound by the AhR), and liver and brain tissues were sampled at 8, 24 and 72 h and RNA was isolated. Changes in gene-specific RNA levels were assessed using commercially available mouse cDNA arrays (Incyte) containing >9600 array elements, including many elements from AhR-mediated genes. Histopathology of the two organs was also assessed. We observed minor histopathological effects and a total of only 29 significant (>2.0-fold) changes in gene expression, most of which occurred in the liver, and most of which could be attributable to an 'acute phase' inflammatory response. These results argue against the hypothesis that PbTx-6 acts via a classic AhR-mediated mechanism to evoke gene expression changes. However, given the avidity with which PbTx-6 binds to the AhR, these findings have important implications for how PbTx's may act in concert with other toxicants that are sensed by the AhR. JF - Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology AU - Walsh, Patrick J AU - Bookman, Richard J AU - Zaias, Julia AU - Mayer, Gregory D AU - Abraham, William AU - Bourdelais, Andrea J AU - Baden, Daniel G AD - NIEHS Marine and Freshwater Biomedical Sciences Center, Rosenstiel School of Marine and Atmospheric Science, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33149, USA. pwalsh@rsmas.miami.edu Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 173 EP - 182 VL - 136 IS - 2 SN - 1096-4959, 1096-4959 KW - Marine Toxins KW - 0 KW - Oxocins KW - brevetoxin KW - 98225-48-0 KW - Index Medicus KW - Molecular Structure KW - Gene Expression Profiling KW - Animals KW - Toxicogenetics KW - Mice KW - Female KW - Genomics KW - Liver -- pathology KW - Liver -- drug effects KW - Brain -- pathology KW - Brain -- drug effects KW - Liver -- metabolism KW - Oxocins -- chemistry KW - Gene Expression Regulation -- drug effects KW - Brain -- metabolism KW - Oxocins -- toxicity KW - Marine Toxins -- toxicity KW - Marine Toxins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75750697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Comparative+biochemistry+and+physiology.+Part+B%2C+Biochemistry+%26+molecular+biology&rft.atitle=Toxicogenomic+effects+of+marine+brevetoxins+in+liver+and+brain+of+mouse.&rft.au=Walsh%2C+Patrick+J%3BBookman%2C+Richard+J%3BZaias%2C+Julia%3BMayer%2C+Gregory+D%3BAbraham%2C+William%3BBourdelais%2C+Andrea+J%3BBaden%2C+Daniel+G&rft.aulast=Walsh&rft.aufirst=Patrick&rft.date=2003-10-01&rft.volume=136&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Comparative+biochemistry+and+physiology.+Part+B%2C+Biochemistry+%26+molecular+biology&rft.issn=10964959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-04 N1 - Date created - 2003-10-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Infect Immun. 2000 Sep;68(9):5026-9 [10948120] Biochem Pharmacol. 2000 Oct 15;60(8):1129-42 [11007951] Life Sci. 1997;60(17):1431-5 [9126863] FEBS Lett. 1997 Jan 13;401(1):73-7 [9003809] Genomics. 1996 Sep 15;36(3):539-42 [8884280] Annu Rev Pharmacol Toxicol. 1995;35:307-40 [7598497] Curr Opin Cell Biol. 1999 Oct;11(5):549-53 [10508654] J Toxicol Environ Health A. 1999 Jul 9;57(5):345-55 [10405188] J Pharmacol Exp Ther. 1998 Feb;284(2):516-25 [9454792] Arch Biochem Biophys. 1997 Jul 15;343(2):149-56 [9224724] Protein Sci. 2001 May;10(5):997-1004 [11316880] Environ Health Perspect. 2001 Apr;109(4):377-81 [11335186] J Hepatol. 2001 Oct;35(4):490-7 [11682033] J Exp Med. 2001 Dec 3;194(11):1617-24 [11733576] Genomics. 2002 Feb;79(2):266-70 [11829497] Arch Biochem Biophys. 2002 Mar 1;399(1):73-80 [11883905] Cell Death Differ. 2002 Jun;9(6):595-7 [12032667] DNA Cell Biol. 2002 Apr;21(4):355-64 [12042074] Eur J Cell Biol. 2002 May;81(5):264-72 [12067062] J Neurosci. 2002 Jun 15;22(12):4918-31 [12077189] Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):1213-8 [12117740] Trends Genet. 2002 Jul;18(7):352-8 [12127775] Glia. 2002 Sep;39(3):279-91 [12203394] Nat Genet. 2002 Oct;32(2):261-6 [12219088] J Biol Chem. 2002 Oct 18;277(42):39102-11 [12167624] Toxicon. 1981;19(4):455-62 [7199210] Toxicon. 1982;20(5):929-32 [6891120] Toxicon. 1984;22(5):783-9 [6084345] FASEB J. 1989 May;3(7):1807-17 [2565840] Toxicon. 1990;28(8):903-10 [2080516] Biochem J. 1991 Jun 1;276 ( Pt 2):273-87 [1646595] Toxicon. 1993 Nov;31(11):1483-6 [8310449] Toxicon. 1994 Jul;32(7):799-805 [7940587] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of laryngeal cancer by occupational chemical exposure in Turkey. AN - 75749813; 14534452 AB - Laryngeal cancer is the second most common cancer among men in Turkey. In this hospital based case-control study, we evaluated laryngeal cancer risks from occupational chemical exposures. We analyzed 940 laryngeal cancer cases and 1519 controls. Occupational history, tobacco, and alcohol use and demographic information were obtained by a questionnaire. The job and industries were classified by special seven-digit codes. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) based on a developed exposure matrix for chemicals, including diesel exhaust, gasoline exhaust, polycyclic aromatic hydrocarbons (PAHs), formaldehyde, and solvents. An excess of laryngeal cancer occurred with diesel exhaust (OR=1.5, 95% CI=1.3-1.9), gasoline exhaust (OR=1.6, 95% CI=1.3-2.0), and PAHs (OR=1.3, 95% CI=1.1-1.6). There was a dose-response relationship for these substances with supraglottic cancers (P<0.000). The PAH association only occurred among those who also had exposure to diesel exhaust. JF - Journal of occupational and environmental medicine AU - Elci, Omur Cinar AU - Akpinar-Elci, Muge AU - Blair, Aaron AU - Dosemeci, Mustafa AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA. oae3@cdc.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 1100 EP - 1106 VL - 45 IS - 10 SN - 1076-2752, 1076-2752 KW - Air Pollutants, Occupational KW - 0 KW - Carcinogens, Environmental KW - Polycyclic Aromatic Hydrocarbons KW - Vehicle Emissions KW - Index Medicus KW - Polycyclic Aromatic Hydrocarbons -- toxicity KW - Humans KW - Air Pollutants, Occupational -- adverse effects KW - Alcohol Drinking KW - Risk Assessment -- methods KW - Smoking KW - Vehicle Emissions -- toxicity KW - Logistic Models KW - Adult KW - Surveys and Questionnaires KW - Case-Control Studies KW - Turkey -- epidemiology KW - Middle Aged KW - Occupations -- classification KW - Male KW - Inhalation Exposure -- adverse effects KW - Laryngeal Neoplasms -- chemically induced KW - Occupational Exposure -- classification KW - Occupational Exposure -- adverse effects KW - Laryngeal Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology KW - Carcinogens, Environmental -- toxicity KW - Occupational Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75749813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+occupational+and+environmental+medicine&rft.atitle=Risk+of+laryngeal+cancer+by+occupational+chemical+exposure+in+Turkey.&rft.au=Elci%2C+Omur+Cinar%3BAkpinar-Elci%2C+Muge%3BBlair%2C+Aaron%3BDosemeci%2C+Mustafa&rft.aulast=Elci&rft.aufirst=Omur&rft.date=2003-10-01&rft.volume=45&rft.issue=10&rft.spage=1100&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+and+environmental+medicine&rft.issn=10762752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-04 N1 - Date created - 2003-10-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical development of 17-allylamino, 17-demethoxygeldanamycin. AN - 75748019; 14529389 AB - 17-allylamino, 17-demethoxygeldanamycin (17AAG; NSC 330507) is the first modulator of heat shock protein 90 (Hsp90) to enter clinical trials. Hsp90 serves a chaperone role to properly fold and deliver client proteins to appropriate intracellular locations. Interest in Hsp90 modulators for the experimental therapeutics of cancer has arisen based on pre-clinical evaluations suggesting that Hsp90 client proteins regulate signaling pathways critical to the molecular economy of many types of tumors, including oncogene signaling, cyclin-dependent kinase activation, steroid hormone receptors, and mediators of invasion and metastasis. Thus, Hsp90-directed agents could affect molecules upon which tumors depend for their proliferation and survival. Initial clinical studies have therefore sought to incorporate assessment of these endpoints into initial clinical evaluations. Three schedules of administration have been supported for initial evaluation in Phase I studies sponsored by the National Cancer Institute (NCI) or supported by NCI and sponsored by Cancer Research UK. In the daily times five schedule, a recommended Phase II dose (RPTD) of 40 mg/m(2) has been reached, while once weekly or three of four weekly schedules are defining RPTDs of 295 and 308 mg/m(2). Toxicity is tolerable and appears dominated by hepatic, gastrointestinal, and constitutional symptoms. Concentrations of drug at peak of ~1700-3000 nM are concordant with concentrations predictive of useful outcomes in pre-clinical model systems. Evidence of modulation of Hsp90 partner molecules has been obtained in both surrogate and some tumor compartments. These very early results encourage additional clinical evaluations of 17AAG and related molecules. JF - Current cancer drug targets AU - Sausville, Edward A AU - Tomaszewski, Joseph E AU - Ivy, Percy AD - Division of Cancer Treatment and Diagnosis, Developmental Therapeutics Program, National Cancer Institute National Cancer Institute, 6130 Executive Blvd, Rm 8018, Rockville, MD 20852, USA. sausville@nih.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 377 EP - 383 VL - 3 IS - 5 SN - 1568-0096, 1568-0096 KW - Benzoquinones KW - 0 KW - HSP90 Heat-Shock Proteins KW - Lactams, Macrocyclic KW - Rifabutin KW - 1W306TDA6S KW - tanespimycin KW - 4GY0AVT3L4 KW - Index Medicus KW - Animals KW - Humans KW - Rifabutin -- analogs & derivatives KW - Rifabutin -- chemical synthesis KW - HSP90 Heat-Shock Proteins -- antagonists & inhibitors KW - Rifabutin -- pharmacokinetics KW - Rifabutin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75748019?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+cancer+drug+targets&rft.atitle=Clinical+development+of+17-allylamino%2C+17-demethoxygeldanamycin.&rft.au=Sausville%2C+Edward+A%3BTomaszewski%2C+Joseph+E%3BIvy%2C+Percy&rft.aulast=Sausville&rft.aufirst=Edward&rft.date=2003-10-01&rft.volume=3&rft.issue=5&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Current+cancer+drug+targets&rft.issn=15680096&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-12 N1 - Date created - 2003-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic dopaminergic neurotoxicity of MPTP and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson's disease. AN - 75743813; 12923073 AB - Parkinson's disease (PD) is a profound movement disorder resulting from progressive degeneration of the nigrostriatal dopaminergic pathway. Although its etiology remains unknown, increasing evidence suggests the involvement of multiple factors such as environmental toxins and genetic susceptibilities in the pathogenesis of PD. In this study using mesencephalic neuron-glia cultures as an in vitro PD model, we demonstrated that the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 0.1-0.5 microM) and an inflammogen lipopolysaccharide (LPS, 0.5 ng/ml) synergistically induced a progressive and selective degeneration of dopaminergic neurons. The synergistic neurotoxicity was observed when both agents were applied either simultaneously or in tandem. The synergistic neurotoxicity was more prominent when lower doses of both agents were applied for a longer period of time. Mechanistically, microglial NADPH oxidase-mediated generation of reactive oxygen species played a pivotal role in the synergistic neurotoxicity: MPTP and LPS synergistically stimulated the NADPH oxidase-mediated release of superoxide free radical; pharmacological inhibition and genetic inactivation of NADPH oxidase prevented superoxide production and the synergistic neurotoxicity. Additionally, inhibition of nitric oxide synthase afforded significant neuroprotection, suggesting the involvement of nitric oxide in the synergistic neurotoxicity. This study lends strong support for a multifactorial etiology of PD and provides clues for therapeutic interventions. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Gao, Hui-Ming AU - Liu, Bin AU - Zhang, Wanqin AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. gao@niehs.nih.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 1957 EP - 1959 VL - 17 IS - 13 KW - Free Radicals KW - 0 KW - Inflammation Mediators KW - Lipopolysaccharides KW - Reactive Oxygen Species KW - Superoxides KW - 11062-77-4 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Coculture Techniques KW - Nerve Degeneration -- chemically induced KW - Mice KW - Free Radicals -- metabolism KW - Rats KW - Inflammation Mediators -- toxicity KW - Superoxides -- metabolism KW - Microglia -- enzymology KW - Dopamine -- analysis KW - NADPH Oxidase -- physiology KW - Models, Neurological KW - Drug Synergism KW - Parkinson Disease, Secondary -- etiology KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Neurons -- cytology KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Lipopolysaccharides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75743813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Synergistic+dopaminergic+neurotoxicity+of+MPTP+and+inflammogen+lipopolysaccharide%3A+relevance+to+the+etiology+of+Parkinson%27s+disease.&rft.au=Gao%2C+Hui-Ming%3BLiu%2C+Bin%3BZhang%2C+Wanqin%3BHong%2C+Jau-Shyong&rft.aulast=Gao&rft.aufirst=Hui-Ming&rft.date=2003-10-01&rft.volume=17&rft.issue=13&rft.spage=1957&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-12 N1 - Date created - 2003-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson's disease. AN - 75743769; 12897068 AB - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages dopaminergic neurons as seen in Parkinson's disease. Although increasing evidence suggests an involvement of glia in MPTP neurotoxicity, the nature of this involvement remains unclear. Exploiting the advantage of cell culture systems, we demonstrated that microglia, but not astroglia, significantly enhanced the progression of MPTP-induced dopaminergic neurodegeneration. Characterization of the temporal relationship between neurodegeneration and microglial activation demonstrates that reactive microgliosis resulting from MPTP-initiated neuronal injury, but not direct activation, underlies the microglia-enhanced MPTP neurotoxicity. Mechanistically, through the release of NADPH oxidase-derived reactive oxygen species, microglia contribute to the progressive neuronal damage. Among the factors measured, the production of extracellular superoxide was the most prominent. NADPH oxidase inhibitor, apocynin, attenuated MPTP-induced dopaminergic neurodegeneration only in the presence of glia. More importantly, dopaminergic neurons from mice lacking NADPH oxidase, a key enzyme for superoxide production in immune cells, are significantly more resistant to MPTP neurotoxicity than those from wild-type controls, and microglia dictate the resistance. This study demonstrates that reactive microgliosis triggered by MPTP-induced neuronal injury and NADPH oxidase-mediated superoxide production in microglia constitute an integral component of MPTP neurotoxicity. This study also suggests that NADPH oxidase may be a promising target for therapeutic interventions in Parkinson's disease. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Gao, Hui-Ming AU - Liu, Bin AU - Zhang, Wanqin AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 1954 EP - 1956 VL - 17 IS - 13 KW - Free Radicals KW - 0 KW - Reactive Oxygen Species KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Coculture Techniques KW - Neurons -- drug effects KW - Astrocytes -- physiology KW - Mice KW - Free Radicals -- metabolism KW - Mice, Knockout KW - Cells, Cultured KW - Neurons -- chemistry KW - Dopamine -- analysis KW - Neurons -- enzymology KW - Models, Neurological KW - Parkinson Disease, Secondary -- etiology KW - Microglia -- physiology KW - Microglia -- enzymology KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - NADPH Oxidase -- physiology KW - NADPH Oxidase -- genetics KW - Microglia -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75743769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Critical+role+of+microglial+NADPH+oxidase-derived+free+radicals+in+the+in+vitro+MPTP+model+of+Parkinson%27s+disease.&rft.au=Gao%2C+Hui-Ming%3BLiu%2C+Bin%3BZhang%2C+Wanqin%3BHong%2C+Jau-Shyong&rft.aulast=Gao&rft.aufirst=Hui-Ming&rft.date=2003-10-01&rft.volume=17&rft.issue=13&rft.spage=1954&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-12 N1 - Date created - 2003-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An overview of recent findings of the Stanley Foundation Bipolar Network (Part I). AN - 75732921; 14525551 AB - Selected recent findings of the Stanley Foundation Bipolar Network are briefly reviewed and their clinical implications discussed. Daily prospective ratings on the NIMH-LCM indicate a high degree of residual depressive morbidity (three times that of hypomania or mania) despite active psychopharmacological treatment with a variety of modalities including mood stabilizers, antidepressants, and benzodiazepines, as well as antipsychotics as necessary. The rates of switching into brief to full hypomania or mania during the use of antidepressants is described, and new data suggesting the potential utility of continuing antidepressants in the small group of patients showing an initial acute and persistent response is noted. Bipolar patients with a history of major environmental adversities in childhood have a more severe course of illness and an increased incidence of suicide attempts compared with those without. Preliminary open data suggest useful antidepressant effects of the atypical antipsychotic quetiapine, while a double-blind randomized controlled study failed to show efficacy of omega-3 fatty acids (6 g of eicosapentaenoic acid compared with placebo for 4 months) in the treatment of either acute depression or rapid cycling. The high prevalence of overweight and increased incidence of antithyroid antibodies in patients with bipolar illness is highlighted. Together, these findings suggest a very high degree of comorbidity and treatment resistance in outpatients with bipolar illness treated in academic settings and the need to develop not only new treatment approaches, but also much earlier illness recognition, diagnosis, and intervention in an attempt to reverse or prevent this illness burden. JF - Bipolar disorders AU - Post, Robert M AU - Leverich, Gabriele S AU - Altshuler, Lori L AU - Frye, Mark A AU - Suppes, Trisha M AU - Keck, Paul E AU - McElroy, Susan L AU - Kupka, Ralph AU - Nolen, Willem A AU - Grunze, Heinz AU - Walden, Jorg AD - Stanley Foundation Bipolar Network and Biological Psychiatry Branch, NIMH, NIH, DHHS, Bethesda, MD 20892-1272, USA. robert.post@nih.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 310 EP - 319 VL - 5 IS - 5 SN - 1398-5647, 1398-5647 KW - Antidepressive Agents KW - 0 KW - Antipsychotic Agents KW - Fatty Acids, Omega-3 KW - Index Medicus KW - Drug Interactions KW - Thyroid Diseases -- complications KW - Fatty Acids, Omega-3 -- therapeutic use KW - Risk Factors KW - Humans KW - Antipsychotic Agents -- therapeutic use KW - Antidepressive Agents -- therapeutic use KW - Meta-Analysis as Topic KW - Comorbidity KW - Bipolar Disorder -- epidemiology KW - Bipolar Disorder -- drug therapy KW - Foundations KW - Information Services -- organization & administration KW - Bipolar Disorder -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75732921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bipolar+disorders&rft.atitle=An+overview+of+recent+findings+of+the+Stanley+Foundation+Bipolar+Network+%28Part+I%29.&rft.au=Post%2C+Robert+M%3BLeverich%2C+Gabriele+S%3BAltshuler%2C+Lori+L%3BFrye%2C+Mark+A%3BSuppes%2C+Trisha+M%3BKeck%2C+Paul+E%3BMcElroy%2C+Susan+L%3BKupka%2C+Ralph%3BNolen%2C+Willem+A%3BGrunze%2C+Heinz%3BWalden%2C+Jorg&rft.aulast=Post&rft.aufirst=Robert&rft.date=2003-10-01&rft.volume=5&rft.issue=5&rft.spage=310&rft.isbn=&rft.btitle=&rft.title=Bipolar+disorders&rft.issn=13985647&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-16 N1 - Date created - 2003-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TGF-beta switches from tumor suppressor to prometastatic factor in a model of breast cancer progression. AN - 75730791; 14523048 AB - The TGF-beta signaling network plays a complex role in carcinogenesis because it has the potential to act as either a tumor suppressor or a pro-oncogenic pathway. Currently, it is not known whether TGF-beta can switch from tumor suppressor to pro-oncogenic factor during the course of carcinogenic progression in a single cell lineage with a defined initiating oncogenic event or whether the specific nature of the response is determined by cell type and molecular etiology. To address this question, we have introduced a dominant negative type II TGF-beta receptor into a series of genetically related human breast-derived cell lines representing different stages in the progression process. We show that decreased TGF-beta responsiveness alone cannot initiate tumorigenesis but that it can cooperate with an initiating oncogenic lesion to make a premalignant breast cell tumorigenic and a low-grade tumorigenic cell line histologically and proliferatively more aggressive. In a high-grade tumorigenic cell line, however, reduced TGF-beta responsiveness has no effect on primary tumorigenesis but significantly decreases metastasis. Our results demonstrate a causal role for loss of TGF-beta responsiveness in promoting breast cancer progression up to the stage of advanced, histologically aggressive, but nonmetastatic disease and suggest that at that point TGF-beta switches from tumor suppressor to prometastatic factor. JF - The Journal of clinical investigation AU - Tang, Binwu AU - Vu, Mary AU - Booker, Timberly AU - Santner, Steven J AU - Miller, Fred R AU - Anver, Miriam R AU - Wakefield, Lalage M AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 1116 EP - 1124 VL - 112 IS - 7 SN - 0021-9738, 0021-9738 KW - Antineoplastic Agents KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Abridged Index Medicus KW - Index Medicus KW - Receptors, Transforming Growth Factor beta -- analysis KW - Neoplasm Transplantation KW - Animals KW - Tumor Cells, Cultured KW - Receptors, Transforming Growth Factor beta -- physiology KW - Humans KW - Neoplasm Metastasis KW - Disease Progression KW - Transplantation, Heterologous KW - Mice KW - Female KW - Cell Transformation, Neoplastic KW - Transforming Growth Factor beta -- pharmacology KW - Mammary Neoplasms, Experimental -- prevention & control KW - Antineoplastic Agents -- pharmacology KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75730791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=TGF-beta+switches+from+tumor+suppressor+to+prometastatic+factor+in+a+model+of+breast+cancer+progression.&rft.au=Tang%2C+Binwu%3BVu%2C+Mary%3BBooker%2C+Timberly%3BSantner%2C+Steven+J%3BMiller%2C+Fred+R%3BAnver%2C+Miriam+R%3BWakefield%2C+Lalage+M&rft.aulast=Tang&rft.aufirst=Binwu&rft.date=2003-10-01&rft.volume=112&rft.issue=7&rft.spage=1116&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-10 N1 - Date created - 2003-10-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Ann Surg. 1995 Aug;222(2):155-62 [7543740] Crit Rev Oncog. 1993;4(5):493-540 [8241322] Cell. 1996 Aug 23;86(4):531-42 [8752208] Cancer Res. 1997 Dec 15;57(24):5564-70 [9407968] Oncogene. 1998 Jul 9;17(1):25-34 [9671311] Curr Biol. 1998 Nov 19;8(23):1243-52 [9822576] Cancer Res. 1999 Oct 1;59(19):4834-42 [10519393] J Natl Cancer Inst. 1999 Dec 15;91(24):2096-101 [10601380] Crit Rev Oncog. 1999;10(4):303-60 [10654929] Histopathology. 2000 Feb;36(2):168-77 [10672063] J Biol Chem. 2000 Apr 21;275(16):12231-6 [10766860] Cell. 2000 Oct 13;103(2):295-309 [11057902] Cancer Res. 2001 Feb 1;61(3):931-4 [11221885] Breast Cancer Res Treat. 2001 Jan;65(2):101-10 [11261825] Nature. 2001 May 17;411(6835):375-9 [11357145] Oncogene. 2001 Aug 16;20(36):5015-24 [11526486] Nat Genet. 2001 Oct;29(2):117-29 [11586292] Curr Opin Genet Dev. 2002 Feb;12(1):22-9 [11790550] Nat Rev Cancer. 2001 Oct;1(1):46-54 [11900251] Aliment Pharmacol Ther. 2002 Apr;16 Suppl 2:115-27 [11966532] J Clin Invest. 2002 Jun;109(12):1551-9 [12070302] J Clin Invest. 2002 Jun;109(12):1607-15 [12070308] Mol Cell Biol. 2002 Dec;22(23):8184-98 [12417722] Cancer Res. 2003 Mar 15;63(6):1371-6 [12649201] Cancer Res. 1988 Dec 15;48(24 Pt 1):6999-7003 [3056609] Cancer Res. 1990 Sep 15;50(18):6075-86 [1975513] Eur J Cancer. 1992;28(2-3):641-4 [1317202] Cancer Res. 1992 Dec 15;52(24):6949-52 [1458485] Am J Pathol. 1993 Aug;143(2):381-9 [8393616] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8392-6 [7690960] Am J Pathol. 1996 Jan;148(1):313-9 [8546221] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dexamethasone blocks the rapid biological effects of 17beta-estradiol in the rat uterus without antagonizing its global genomic actions. AN - 75730161; 14519664 AB - Estrogens and glucocorticoids have opposing effects on the female reproductive tract, but the molecular basis for this antagonism is poorly understood. We therefore examined the biological and transcriptional programs induced by estrogens and glucocorticoids in the uterus of immature female rats. Estradiol 17beta (E2) rapidly induced morphological changes reminiscent of an acute inflammatory response, including infiltration of eosinophils, edema in the stroma and myometrium, and a decrease in the height of luminal epithelial cells, whereas dexamethasone (Dex) only altered stromal cell morphology. When coadministered with E2, Dex completely blocked the proinflammatory effects of E2. Surprisingly, examination of E2 and Dex effects on gene expression using cDNA microarrays and real-time PCR revealed that these hormones had similar effects on the expression of many genes and that very few genes displayed antagonistic regulation. Together, these results indicate strong discord between the early biologic and genomic actions of estrogens and glucocorticoids and highlight a complex regulatory role for glucocorticoids and GR in the mammalian uterus. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Rhen, Turk AU - Grissom, Sherry AU - Afshari, Cynthia AU - Cidlowski, John A AD - Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Dr., Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 1849 EP - 1870 VL - 17 IS - 13 KW - Estrogen Antagonists KW - 0 KW - Glucocorticoids KW - Receptors, Estrogen KW - Receptors, Glucocorticoid KW - Estradiol KW - 4TI98Z838E KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Animals KW - Drug Interactions KW - Estradiol -- pharmacology KW - Receptors, Estrogen -- immunology KW - Receptors, Estrogen -- analysis KW - Genome KW - Rats KW - Gene Expression Profiling KW - Receptors, Glucocorticoid -- analysis KW - Gene Expression Regulation -- drug effects KW - Time Factors KW - Immunohistochemistry KW - Female KW - Receptors, Glucocorticoid -- immunology KW - Uterus -- metabolism KW - Estrogen Antagonists -- pharmacology KW - Dexamethasone -- pharmacology KW - Uterus -- anatomy & histology KW - Uterus -- drug effects KW - Glucocorticoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75730161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dexamethasone+blocks+the+rapid+biological+effects+of+17beta-estradiol+in+the+rat+uterus+without+antagonizing+its+global+genomic+actions.&rft.au=Rhen%2C+Turk%3BGrissom%2C+Sherry%3BAfshari%2C+Cynthia%3BCidlowski%2C+John+A&rft.aulast=Rhen&rft.aufirst=Turk&rft.date=2003-10-01&rft.volume=17&rft.issue=13&rft.spage=1849&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-12 N1 - Date created - 2003-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical pharmacology of flavopiridol following a 72-hour continuous infusion. AN - 75725166; 14519054 AB - Flavopiridol, a novel flavone derivative, inhibits cyclin-dependent kinase-1. We initiated a Phase I trial in patients with refractory solid tumors to determine the maximum tolerated dose and characterize the adverse effect profile. To characterize the clinical pharmacology of flavopiridol. Serial plasma samples were collected and analyzed by HPLC using electrochemical detection. The pharmacokinetics were analyzed by noncompartmental analysis. Enterohepatic recirculation was studied by analyzing fecal samples, with an attempt to correlate cholecystokinin and post-infusional peak concentrations. The plasma protein binding was studied using equilibrium dialysis. Seventy-six patients were treated with flavopiridol at 13 dose levels for a total of 504 cycles of treatment. The average steady-state concentration was 26.5 and 253 nM at 4 and 122.5 mg/m2, respectively. The clearance ranged from 49.9 to 2943 mL/min, with nonlinearity at doses >50 mg/m2/d. A post-infusional increase in plasma flavopiridol concentrations was noted in a subset of patients and generally occurred between 3 and 24 hours after the end of infusion. Flavopiridol was found in fecal matter, suggesting enterohepatic recirculation. There was nonsaturable plasma protein binding of flavopiridol (fu = 6%). The dose-limiting toxicity for the Phase I trial of flavopiridol was secretory diarrhea. We failed to identify a clear relationship between dose or concentration and diarrhea. At 50 and 78 mg/m2/d, the mean steady-state plasma concentrations were 278 and 390 nM. These concentrations were well above those noted for in vitro antiproliferative activity. Nonlinear elimination was observed at doses above 50 mg/m2/d, and postinfusional peaks appear to be related to enterohepatic recirculation. JF - The Annals of pharmacotherapy AU - Rudek, Michelle A AU - Bauer, Kenneth S AU - Lush, Richard M AU - Stinson, Sherman F AU - Senderowicz, Adrian M AU - Headlee, Donna J AU - Arbuck, Susan G AU - Cox, Michael C AU - Murgo, Anthony J AU - Sausville, Edward A AU - Figg, William D AD - Clinical Pharmacology Research Core, National Cancer Institute, Bethesda, MD, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 1369 EP - 1374 VL - 37 IS - 10 SN - 1060-0280, 1060-0280 KW - Flavonoids KW - 0 KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - Index Medicus KW - Neoplasms -- drug therapy KW - Infusions, Intravenous KW - Food KW - Humans KW - Aged KW - Feces -- chemistry KW - Diarrhea -- chemically induced KW - Protein Binding -- drug effects KW - Adult KW - Diarrhea -- complications KW - Middle Aged KW - Maximum Tolerated Dose KW - Time Factors KW - Female KW - Male KW - Piperidines -- pharmacokinetics KW - Piperidines -- administration & dosage KW - Flavonoids -- pharmacokinetics KW - Flavonoids -- metabolism KW - Piperidines -- metabolism KW - Pharmacology, Clinical KW - Flavonoids -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75725166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+pharmacotherapy&rft.atitle=Clinical+pharmacology+of+flavopiridol+following+a+72-hour+continuous+infusion.&rft.au=Rudek%2C+Michelle+A%3BBauer%2C+Kenneth+S%3BLush%2C+Richard+M%3BStinson%2C+Sherman+F%3BSenderowicz%2C+Adrian+M%3BHeadlee%2C+Donna+J%3BArbuck%2C+Susan+G%3BCox%2C+Michael+C%3BMurgo%2C+Anthony+J%3BSausville%2C+Edward+A%3BFigg%2C+William+D&rft.aulast=Rudek&rft.aufirst=Michelle&rft.date=2003-10-01&rft.volume=37&rft.issue=10&rft.spage=1369&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+pharmacotherapy&rft.issn=10600280&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-26 N1 - Date created - 2003-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Speed kills: cellular and molecular bases of methamphetamine-induced nerve terminal degeneration and neuronal apoptosis. AN - 75723526; 14519657 AB - Methamphetamine (METH) is a drug of abuse that has long been known to damage monoaminergic systems in the mammalian brain. Recent reports have provided conclusive evidence that METH can cause neuropathological changes in the rodent brain via apoptotic mechanisms akin to those reported in various models of neuronal death. The purpose of this review is to provide an interim account for a role of oxygen-based radicals and the participation of transcription factors and the involvement of cell death genes in METH-induced neurodegeneration. We discuss data suggesting the participation of endoplasmic reticulum and mitochondria-mediated activation of caspase-dependent and -independent cascades in the manifestation of METH-induced apoptosis. Studies that use more comprehensive approaches to gene expression profiling should allow us to draw more instructive molecular portraits of the complex plastic and degenerative effects of this drug. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Cadet, Jean Lud AU - Jayanthi, Subramaniam AU - Deng, Xiaolin AD - Molecular Neuropsychiatry Branch, NIH, NIDA, Intramural Research Program, Department of Health and Human Services, 5500 Nathan Shock Dr., Baltimore, Maryland 21224, USA. jcadet@intra.nida.nih.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 1775 EP - 1788 VL - 17 IS - 13 KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Rats KW - Animals KW - Presynaptic Terminals -- drug effects KW - Humans KW - Cytoprotection KW - Mice KW - Models, Biological KW - Signal Transduction KW - Neurons -- pathology KW - Apoptosis KW - Neurotoxicity Syndromes -- etiology KW - Methamphetamine -- pharmacology KW - Nerve Degeneration -- chemically induced KW - Neurotoxicity Syndromes -- metabolism KW - Neurotoxicity Syndromes -- pathology KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75723526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Speed+kills%3A+cellular+and+molecular+bases+of+methamphetamine-induced+nerve+terminal+degeneration+and+neuronal+apoptosis.&rft.au=Cadet%2C+Jean+Lud%3BJayanthi%2C+Subramaniam%3BDeng%2C+Xiaolin&rft.aulast=Cadet&rft.aufirst=Jean&rft.date=2003-10-01&rft.volume=17&rft.issue=13&rft.spage=1775&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-12 N1 - Date created - 2003-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alteration in calcium channel properties is responsible for the neurotoxic action of a familial frontotemporal dementia tau mutation. AN - 75713870; 14511120 AB - Tau, a microtubule binding protein, is not only a major component of neurofibrillary tangles in Alzheimer's disease, but also a causative gene for hereditary frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We show here that an FTDP-17 tau mutation (V337M) in SH-SY5Y cells reduces microtubule polymerization, increases voltage-dependent calcium current (ICa) density, and decreases ICa rundown. The reduced rundown of ICa by V337M was significantly inhibited by nifedipine (L-type Ca channel blocker), whereas omega-conotoxin GVIA (N-type Ca channel blocker) showed smaller effects, indicating that tau mutations affect L-type calcium channel activity. The depolarization-induced increase in intracellular calcium was also significantly augmented by the V337M tau mutation. Treatment with a microtubule polymerizing agent (taxol), an adenylyl cyclase inhibitor, or a protein kinase A (PKA) inhibitor, counteracted the effects of mutant tau on ICa. Taxol also attenuated the Ca2+ response to depolarization in cells expressing mutant tau. Apoptosis in SH-SY5Y cells induced by serum deprivation was exacerbated by the V337M mutation, and nifedipine, taxol, and a PKA inhibitor significantly protected cells against apoptosis. Our results indicate that a tau mutation which decreases its microtubule-binding ability augments calcium influx by depolymerizing microtubules and activating adenylyl cyclase and PKA. JF - Journal of neurochemistry AU - Furukawa, Katsutoshi AU - Wang, Yue AU - Yao, Pamela J AU - Fu, Weiming AU - Mattson, Mark P AU - Itoyama, Yasuto AU - Onodera, Hiroshi AU - D'Souza, Ian AU - Poorkaj, Parvone H AU - Bird, Thomas D AU - Schellenberg, Gerard D AD - Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. furukawaka@grc.nia.nih.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 427 EP - 436 VL - 87 IS - 2 SN - 0022-3042, 0022-3042 KW - Calcium Channels KW - 0 KW - Calcium Channels, L-Type KW - tau Proteins KW - Cyclic AMP KW - E0399OZS9N KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Humans KW - Microtubules -- metabolism KW - Membrane Potentials -- physiology KW - Cell Death -- drug effects KW - Neuroblastoma -- metabolism KW - Calcium -- metabolism KW - Calcium Channels, L-Type -- drug effects KW - Patch-Clamp Techniques KW - Neuroblastoma -- drug therapy KW - Neurons -- cytology KW - Cyclic AMP -- metabolism KW - Calcium Channels, L-Type -- metabolism KW - Calcium Channels, L-Type -- genetics KW - Mutation KW - Cell Line KW - Calcium Channels -- metabolism KW - tau Proteins -- toxicity KW - Dementia -- genetics KW - Calcium Channels -- drug effects KW - tau Proteins -- genetics KW - Dementia -- complications KW - Parkinsonian Disorders -- genetics KW - Parkinsonian Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75713870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alteration+in+calcium+channel+properties+is+responsible+for+the+neurotoxic+action+of+a+familial+frontotemporal+dementia+tau+mutation.&rft.au=Furukawa%2C+Katsutoshi%3BWang%2C+Yue%3BYao%2C+Pamela+J%3BFu%2C+Weiming%3BMattson%2C+Mark+P%3BItoyama%2C+Yasuto%3BOnodera%2C+Hiroshi%3BD%27Souza%2C+Ian%3BPoorkaj%2C+Parvone+H%3BBird%2C+Thomas+D%3BSchellenberg%2C+Gerard+D&rft.aulast=Furukawa&rft.aufirst=Katsutoshi&rft.date=2003-10-01&rft.volume=87&rft.issue=2&rft.spage=427&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 - 2003-11-06 N1 - Date created - 2003-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel consensus DNA-binding sequence for BRCA1 protein complexes. AN - 73671041; 14502648 AB - Increasing evidence continues to emerge supporting the early hypothesis that BRCA1 might be involved in transcriptional processes. BRCA1 physically associates with more than 15 different proteins involved in transcription and is paradoxically involved in both transcriptional activation and repression. However, the underlying mechanism by which BRCA1 affects the gene expression of various genes remains speculative. In this study, we provide evidence that BRCA1 protein complexes interact with specific DNA sequences. We provide data showing that the upstream stimulatory factor 2 (USF2) physically associates with BRCA1 and is a component of this DNA-binding complex. Interestingly, these DNA-binding complexes are downregulated in breast cancer cell lines containing wild-type BRCA1, providing a critical link between modulations of BRCA1 function in sporadic breast cancers that do not involve germline BRCA1 mutations. The functional specificity of BRCA1 tumor suppression for breast and ovarian tissues is supported by our experiments, which demonstrate that BRCA1 DNA-binding complexes are modulated by serum and estrogen. Finally, functional analysis indicates that missense mutations in BRCA1 that lead to subsequent cancer susceptibility may result in improper gene activation. In summary, these findings establish a role for endogenous BRCA1 protein complexes in transcription via a defined DNA-binding sequence and indicate that one function of BRCA1 is to co-regulate the expression of genes involved in various cellular processes. Published 2003 Wiley-Liss, Inc. JF - Molecular carcinogenesis AU - Cable, P LouAnn AU - Wilson, Cindy A AU - Calzone, Frank J AU - Rauscher, Frank J AU - Scully, Ralph AU - Livingston, David M AU - Li, Leping AU - Blackwell, Courtney B AU - Futreal, P Andrew AU - Afshari, Cynthia A AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 85 EP - 96 VL - 38 IS - 2 SN - 0899-1987, 0899-1987 KW - BRCA1 Protein KW - 0 KW - DNA-Binding Proteins KW - Index Medicus KW - Humans KW - Breast KW - Molecular Sequence Data KW - Gene Expression Regulation KW - Transcriptional Activation KW - Cell Line KW - Binding Sites KW - Base Sequence KW - BRCA1 Protein -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73671041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Novel+consensus+DNA-binding+sequence+for+BRCA1+protein+complexes.&rft.au=Cable%2C+P+LouAnn%3BWilson%2C+Cindy+A%3BCalzone%2C+Frank+J%3BRauscher%2C+Frank+J%3BScully%2C+Ralph%3BLivingston%2C+David+M%3BLi%2C+Leping%3BBlackwell%2C+Courtney+B%3BFutreal%2C+P+Andrew%3BAfshari%2C+Cynthia+A&rft.aulast=Cable&rft.aufirst=P&rft.date=2003-10-01&rft.volume=38&rft.issue=2&rft.spage=85&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 - 2003-10-29 N1 - Date created - 2003-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perforin and the granule exocytosis cytotoxicity pathway. AN - 73667075; 14499260 AB - Perforin defects have been identified in humans with familial hematophagocytic lymphohistiocytosis. The pathology of these patients has dramatically illustrated an under-appreciated role for perforin in the regulation of T-cell responses in vivo, and experimental studies are shedding light on the mechanisms involved. The detailed molecular mechanisms of perforin's mandatory role in the cytotoxic T lymphocyte (CTL)-mediated granule exocytosis death pathway and of granzyme entry into target cells remain unclear. In model systems measuring apoptosis by granzyme B and sublytic perforin, pore formation is undetectable during granzyme entry. Selfprotection of cytotoxic lymphocytes after degranulation can be explained by surface expression of the granule protease cathepsin B, as shown by suicidal degranulation in the presence of specific inhibitors. JF - Current opinion in immunology AU - Catalfamo, Marta AU - Henkart, Pierre A AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 4B36, 9000 Rockville Pike, Bethesda, MD 20892-1360, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 522 EP - 527 VL - 15 IS - 5 SN - 0952-7915, 0952-7915 KW - Membrane Glycoproteins KW - 0 KW - Pore Forming Cytotoxic Proteins KW - Protease Inhibitors KW - Perforin KW - 126465-35-8 KW - GZMB protein, human KW - EC 3.4.21.- KW - Granzymes KW - Serine Endopeptidases KW - Index Medicus KW - Animals KW - Humans KW - Chick Embryo KW - Protease Inhibitors -- immunology KW - Cell Death KW - Cytotoxicity Tests, Immunologic KW - Serine Endopeptidases -- immunology KW - Membrane Glycoproteins -- physiology KW - Exocytosis -- immunology KW - Cytoplasmic Granules -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Cytoplasmic Granules -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73667075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+immunology&rft.atitle=Perforin+and+the+granule+exocytosis+cytotoxicity+pathway.&rft.au=Catalfamo%2C+Marta%3BHenkart%2C+Pierre+A&rft.aulast=Catalfamo&rft.aufirst=Marta&rft.date=2003-10-01&rft.volume=15&rft.issue=5&rft.spage=522&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+immunology&rft.issn=09527915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-02 N1 - Date created - 2003-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolism of (R)-(+)-menthofuran in Fischer-344 rats: identification of sulfonic acid metabolites. AN - 73661469; 12975329 AB - (R)-(+)-Menthofuran is a metabolite of (R)-(+)-pulegone, the chief constituent of pennyroyal oil. Menthofuran has been shown to account for a significant percentage of pulegone toxicity through further metabolism to a reactive intermediate, an enonal (2-Z-(2'-keto-4'-methylcyclohexylidene)propanal). Hydration of the enonal followed by a 1,4-dehydration and rearrangement gives rise to diastereomeric (-)-mintlactone and (+)-isomintlactone (mintlactones). We have conducted disposition studies on pulegone as part of the National Toxicology Program initiative in herbal medicines and dietary supplements, and have reported previously unknown urinary metabolites of pulegone. Comparative metabolism studies of 14C-labeled menthofuran in Fischer-344 (F344) rats were carried out to determine urinary metabolites of pulegone that are derived from the menthofuran pathway. Three sulfonic acid metabolites, namely, hexahydro-3,6-dimethyl-1-(2-sulfoethyl)-2H-indol-2-one, hexahydro-3,6-dimethyl-7a-sulfo-2(3H)-benzofuranone, and 2-sulfomenthofuran, were identified in urine of treated rats. Formation of these metabolites may be derived from reactions of the enonal with taurine or glutathione (GSH) (or sulfite ion). Other identified urinary metabolites of menthofuran could be attributed to further metabolism of mintlactones. Further hydroxylation of mintlactones could give 7a-hydroxymintlactone and 6,7a-dihydroxymintlactone. Glucuronidation or reduction of 7a-hydroxymintlactone could give rise to the major metabolites 7a-hydroxymintlactone glucuronide and 2-[2'-keto-4'-methylcyclohexyl]propionic acids. Glucuronidation or repeated hydroxylation/dehydration of 2-[2'-keto-4'-methylcyclohexyl]propionic acids could result in formation of hexahydro-3,6-dimethyl-7a-hydroxy-2(3H)-benzofuranone glucuronide and 2-(2'-hydroxy-4'-methylphenyl)propionic acid. 2-(Glutathion-S-yl)menthofuran, a GSH conjugate of the enonal that has been partially characterized in bile of rats dosed with pulegone, is at most a minor biliary metabolite of menthofuran in rats. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Chen, L-J AU - Lebetkin, E H AU - Burka, L T AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. ferguso2@niehs.nih.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 1208 EP - 1213 VL - 31 IS - 10 SN - 0090-9556, 0090-9556 KW - Monoterpenes KW - 0 KW - Sulfonic Acids KW - menthofuran KW - 494-90-6 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Male KW - Female KW - Monoterpenes -- metabolism KW - Monoterpenes -- chemistry KW - Sulfonic Acids -- analysis KW - Sulfonic Acids -- metabolism KW - Monoterpenes -- pharmacology KW - Sulfonic Acids -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73661469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Metabolism+of+%28R%29-%28%2B%29-menthofuran+in+Fischer-344+rats%3A+identification+of+sulfonic+acid+metabolites.&rft.au=Chen%2C+L-J%3BLebetkin%2C+E+H%3BBurka%2C+L+T&rft.aulast=Chen&rft.aufirst=L-J&rft.date=2003-10-01&rft.volume=31&rft.issue=10&rft.spage=1208&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-20 N1 - Date created - 2003-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neonatal diethylstilbestrol exposure induces persistent elevation of c-fos expression and hypomethylation in its exon-4 in mouse uterus. AN - 73659032; 14502647 AB - Perinatal exposure to diethylstilbestrol (DES) induces reproductive tract cancers later in life in both humans and animals. Because there is no clear evidence that perinatal DES exposure induces gene mutation, we proposed that perinatal DES exposure causes epigenetic methylation changes that result in persistent alterations in gene expression, leading to tumorigenesis. The proto-oncogene c-fos is one of the immediately induced genes in uterine epithelium after estrogen simulation and a key player in uterine carcinogenesis. Here, we investigated c-fos expression in mice neonatally exposed to DES (2 microg/pup/day on postnatal days 1-5). The mRNA levels of c-fos in uteri of neonatal DES-treated mice were persistently 1.4-1.9-fold higher than that in the control mice from day 5 to day 60. Overall, the uterine c-fos expression level in the neonatal DES-exposed group was significantly higher than that in the control group. After examination of the methylation status of the c-fos gene, we found that the CpGs in promoter and intron-1 regions were completely unmethylated. In exon-4, from day 17 to day 60, the percentage of unmethylated CpGs was higher in neonatal DES-exposed mice uteri than that in control (42%, 51%, 47%, and 42% in DES-exposed mice vs 33%, 34%, 33%, and 21% in control mice at day 17, 21, 30, and 60, respectively). These results suggest that perinatal DES exposure may permanently alter gene expression and methylation, and the methylation modification may occur in either the promoter regions or other regulatory sites in the gene. Published 2003 Wiley-Liss, Inc. JF - Molecular carcinogenesis AU - Li, Shuanfang AU - Hansman, Roberta AU - Newbold, Retha AU - Davis, Barbara AU - McLachlan, John A AU - Barrett, J Carl AD - Laboratory of Biosystems and Cancer, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 78 EP - 84 VL - 38 IS - 2 SN - 0899-1987, 0899-1987 KW - Proto-Oncogene Proteins c-fos KW - 0 KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals KW - Base Sequence KW - Exons KW - Gene Expression KW - Mice KW - Female KW - Uterus -- metabolism KW - DNA Methylation KW - Diethylstilbestrol -- pharmacology KW - Genes, fos KW - Diethylstilbestrol -- administration & dosage KW - Uterus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73659032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neonatal+diethylstilbestrol+exposure+induces+persistent+elevation+of+c-fos+expression+and+hypomethylation+in+its+exon-4+in+mouse+uterus.&rft.au=Li%2C+Shuanfang%3BHansman%2C+Roberta%3BNewbold%2C+Retha%3BDavis%2C+Barbara%3BMcLachlan%2C+John+A%3BBarrett%2C+J+Carl&rft.aulast=Li&rft.aufirst=Shuanfang&rft.date=2003-10-01&rft.volume=38&rft.issue=2&rft.spage=78&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 - 2003-10-29 N1 - Date created - 2003-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Current treatment approaches to leishmaniasis. AN - 73651052; 14501991 AB - The leishmaniases consist of cutaneous, mucosal, and visceral syndromes. The classic treatment is with pentavalent antimonials. The disadvantages of the antimonials are their requirement for intramuscular or intravenous injection each day for 20-28 days, their toxicity, and the recent development of resistance in regions such as India. Amphotericin B is a potent secondary agent, but is also compromised by its parenteral nature and toxicity. Clinical investigation of treatment agents from January 2000 to January 2003 is reviewed to determine if there are new agents that can be used. A large number of pilot studies on visceral and cutaneous leishmaniasis have been performed. There can be more confidence in the visceral studies because visceral disease is incurable if untreated, and because large numbers of patients have been treated in highly endemic regions such as India. There is less confidence in pilot studies of the cutaneous disease, because most are uncontrolled, and there is a variable, and often high, cure rate without treatment. Liposomal amphotericin B, which is injected infrequently and is easily tolerated, is virtually 100% effective for Indian visceral disease at a total dose of 15 mg/kg and is 90% effective at a dose of 5-10 mg/kg. The oral agent, miltefosine, is more than 95% effective for Indian visceral disease. Fluconazole treatment for 6 weeks speeds up the already-rapid cure rate of cutaneous disease due to Leishmania major. JF - Current opinion in infectious diseases AU - Berman, Jonathan AD - Office of Clinical and Regulatory Affairs, National Center For Complementary and Alternative Medicine, National Institutes of Health, 6707 Democracy Boulevard, Suite 401 Bethesda, MD 20892, USA. Bermanjo@mail.nih.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 397 EP - 401 VL - 16 IS - 5 SN - 0951-7375, 0951-7375 KW - Antiprotozoal Agents KW - 0 KW - Phosphorylcholine KW - 107-73-3 KW - miltefosine KW - 53EY29W7EC KW - Paromomycin KW - 61JJC8N5ZK KW - Pentamidine KW - 673LC5J4LQ KW - Amphotericin B KW - 7XU7A7DROE KW - Fluconazole KW - 8VZV102JFY KW - Antimony Sodium Gluconate KW - V083S0159D KW - Index Medicus KW - Fluconazole -- therapeutic use KW - Antimony Sodium Gluconate -- therapeutic use KW - Humans KW - Clinical Trials as Topic KW - Amphotericin B -- therapeutic use KW - Pentamidine -- therapeutic use KW - Paromomycin -- therapeutic use KW - Phosphorylcholine -- therapeutic use KW - Leishmaniasis -- drug therapy KW - Antiprotozoal Agents -- therapeutic use KW - Phosphorylcholine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73651052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+infectious+diseases&rft.atitle=Current+treatment+approaches+to+leishmaniasis.&rft.au=Berman%2C+Jonathan&rft.aulast=Berman&rft.aufirst=Jonathan&rft.date=2003-10-01&rft.volume=16&rft.issue=5&rft.spage=397&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+infectious+diseases&rft.issn=09517375&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-16 N1 - Date created - 2003-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - STAT1 plays an essential role in LPS/D-galactosamine-induced liver apoptosis and injury. AN - 73630370; 12816762 AB - Interferon-gamma (IFN-gamma) has been implicated in liver damage in animal models and chronic hepatitis C infection; however, the underlying mechanism is not clear. Here we examined the role of STAT1, a key signaling molecule for IFN-gamma, in a model of murine hepatitis induced by the injection of LPS/D-galactosamine and in human hepatoma Hep3B cells. STAT1 is rapidly activated and highly induced after injection of LPS/D-galactosamine. Both overexpression of STAT1 and hepatocellular damage are located in the same pericentral region. Disruption of the STAT1 gene abolishes LPS/D-galactosamine-induced liver injury. Studies from IFN-gamma-deficient mice indicate that IFN-gamma is the major cytokine responsible for activation and hyperexpression of STAT1 in LPS/D-galactosamine-induced hepatitis. Hep3B cells overexpressing dominant negative STAT1 are resistant to IFN-gamma and IFN-gamma + TNF-alpha-induced cell death, whereas Hep3B cells overexpressing wild-type STAT1 are more susceptible to cell death. Taken together, these findings suggest that STAT1 plays an essential role in LPS/D-galactosamine-induced liver apoptosis and injury. JF - American journal of physiology. Gastrointestinal and liver physiology AU - Kim, Won-Ho AU - Hong, Feng AU - Radaeva, Svetlana AU - Jaruga, Barbara AU - Fan, Saijun AU - Gao, Bin AD - Section on Liver Biology, National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - G761 EP - G768 VL - 285 IS - 4 SN - 0193-1857, 0193-1857 KW - DNA-Binding Proteins KW - 0 KW - Lipopolysaccharides KW - STAT1 Transcription Factor KW - Stat1 protein, mouse KW - Trans-Activators KW - Tumor Necrosis Factor-alpha KW - Phosphotyrosine KW - 21820-51-9 KW - Galactosamine KW - 7535-00-4 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Animals KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Phosphotyrosine -- metabolism KW - Interferon-gamma -- pharmacology KW - Mice KW - Mice, Inbred BALB C KW - Mice, Knockout KW - Hepatocytes -- chemistry KW - Phosphorylation KW - Transfection KW - Hepatocytes -- ultrastructure KW - Interferon-gamma -- deficiency KW - Liver Diseases -- pathology KW - Flow Cytometry KW - Interferon-gamma -- physiology KW - DNA Fragmentation KW - Cell Line KW - Galactosamine -- pharmacology KW - Trans-Activators -- deficiency KW - Chemical and Drug Induced Liver Injury -- etiology KW - DNA-Binding Proteins -- deficiency KW - Trans-Activators -- genetics KW - Lipopolysaccharides -- pharmacology KW - Apoptosis -- drug effects KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73630370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+physiology.+Gastrointestinal+and+liver+physiology&rft.atitle=STAT1+plays+an+essential+role+in+LPS%2FD-galactosamine-induced+liver+apoptosis+and+injury.&rft.au=Kim%2C+Won-Ho%3BHong%2C+Feng%3BRadaeva%2C+Svetlana%3BJaruga%2C+Barbara%3BFan%2C+Saijun%3BGao%2C+Bin&rft.aulast=Kim&rft.aufirst=Won-Ho&rft.date=2003-10-01&rft.volume=285&rft.issue=4&rft.spage=G761&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Gastrointestinal+and+liver+physiology&rft.issn=01931857&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-21 N1 - Date created - 2003-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV-2 derived lentiviral vectors: gene transfer in Parkinson's and Fabry disease models in vitro. AN - 73594785; 12938190 AB - Lentiviral vectors are prime candidate vectors for gene transfer into dividing and non-dividing cells, including neuronal cells and stem cells. For safety, HIV-2 lentiviral vectors may be better suited for gene transfer in humans than HIV-1 lentiviral vectors. HIV-2 vectors cross-packaged in HIV-1 cores may be even safer. Demonstration of the efficacy of these vectors in disease models will validate their usefulness. Parkinson's disease and Fabry disease provide excellent models for validation. Parkinson's disease is a focal degeneration of dopaminergic neurons in the brain with progressive loss of ability to produce the neurotransmitter dopamine. Current treatment entails administration of increasing doses of L-dopa, with attendant toxicity. We explore here the hypothesis that gene transfer of aromatic acid decarboxylase (AADC), a key enzyme in the pathway, will make neuronal cells more efficiently convert L-dopa into dopamine. Fabry disease on the other hand is a monogenic inherited disease, characterized by alpha-galactosidase A (AGA) deficiency, resulting in glycolipid accumulation in several cell types, including fibroblasts. Animal models for preclinical investigations of both of these diseases are available. We have designed monocistronic HIV-1 and HIV-2 vectors with the AADC transgene and monocistronic and bicistronic HIV-2 vectors with the AGA and puromycin resistance transgenes. They were packaged with either HIV-2 cores or HIV-1 cores (hybrid vectors). Gene transfer of AADC gene in neuronal cells imparted the ability on the transduced cells to efficiently convert L-dopa into dopamine. Similarly, the AGA vectors induced Fabry fibroblasts to produce high levels of AGA enzyme and caused rapid clearance of the glycolipids from the cells. Both monocistronic and bicistronic vectors were effective. Thus, the insertion of a second gene downstream in the bicistronic vector was not deleterious. In addition, both the self-packaged vectors and the cross-packaged hybrid vectors were effective in gene transfer. Copyright 2003 Wiley-Liss, Inc. JF - Journal of medical virology AU - D'Costa, Jenice AU - Harvey-White, Judith AU - Qasba, Pankaj AU - Limaye, Advait AU - Kaneski, Christine R AU - Davis-Warren, Alberta AU - Brady, Roscoe O AU - Bankiewicz, Krys S AU - Major, Eugene O AU - Arya, Suresh K AD - Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 173 EP - 182 VL - 71 IS - 2 SN - 0146-6615, 0146-6615 KW - alpha-Galactosidase KW - EC 3.2.1.22 KW - Aromatic-L-Amino-Acid Decarboxylases KW - EC 4.1.1.28 KW - Index Medicus KW - Cells, Cultured KW - Humans KW - Transgenes KW - Transduction, Genetic KW - Fabry Disease -- physiopathology KW - Genetic Therapy -- methods KW - alpha-Galactosidase -- genetics KW - Aromatic-L-Amino-Acid Decarboxylases -- metabolism KW - Parkinson Disease -- physiopathology KW - Models, Biological KW - Aromatic-L-Amino-Acid Decarboxylases -- genetics KW - alpha-Galactosidase -- metabolism KW - HIV-1 -- genetics KW - Fibroblasts -- virology KW - Fibroblasts -- enzymology KW - Gene Transfer Techniques KW - Genetic Vectors KW - Neurons -- enzymology KW - HIV-2 -- genetics KW - Neurons -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73594785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medical+virology&rft.atitle=HIV-2+derived+lentiviral+vectors%3A+gene+transfer+in+Parkinson%27s+and+Fabry+disease+models+in+vitro.&rft.au=D%27Costa%2C+Jenice%3BHarvey-White%2C+Judith%3BQasba%2C+Pankaj%3BLimaye%2C+Advait%3BKaneski%2C+Christine+R%3BDavis-Warren%2C+Alberta%3BBrady%2C+Roscoe+O%3BBankiewicz%2C+Krys+S%3BMajor%2C+Eugene+O%3BArya%2C+Suresh+K&rft.aulast=D%27Costa&rft.aufirst=Jenice&rft.date=2003-10-01&rft.volume=71&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Journal+of+medical+virology&rft.issn=01466615&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-25 N1 - Date created - 2003-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The IARC evaluation of DEHP excludes key papers demonstrating carcinogenic effects. AN - 71592076; 15688552 JF - International journal of occupational and environmental health AU - Melnick, Ronald L AU - Brody, Charlotte AU - DiGangi, Joseph AU - Huff, James AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. PY - 2003 SP - 400 EP - 402 VL - 9 IS - 4 SN - 1077-3525, 1077-3525 KW - Diethylhexyl Phthalate KW - C42K0PH13C KW - Index Medicus KW - Rats KW - Peer Review, Research KW - Animals KW - Humans KW - Carcinogenicity Tests KW - Diethylhexyl Phthalate -- classification KW - Pancreatic Neoplasms -- chemically induced KW - Diethylhexyl Phthalate -- toxicity KW - International Agencies -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71592076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+occupational+and+environmental+health&rft.atitle=The+IARC+evaluation+of+DEHP+excludes+key+papers+demonstrating+carcinogenic+effects.&rft.au=Melnick%2C+Ronald+L%3BBrody%2C+Charlotte%3BDiGangi%2C+Joseph%3BHuff%2C+James&rft.aulast=Melnick&rft.aufirst=Ronald&rft.date=2003-10-01&rft.volume=9&rft.issue=4&rft.spage=400&rft.isbn=&rft.btitle=&rft.title=International+journal+of+occupational+and+environmental+health&rft.issn=10773525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-03 N1 - Date created - 2005-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Normal tissue tolerance to intraoperative radiotherapy. AN - 71555220; 14989124 AB - Much experimental evidence has been accumulated assessing the tolerance of various tissues to IORT, and much of the tolerance data have resulted from the use of canine models. Guidelines of IORT tissue tolerance established in experimental models have been used in the clinical application of IORT at numerous institutions. Although the radiotolerance of differing tissues can vary among species, sufficient clinical experience has accumulated to validate the canine tissue tolerance model as representative of human tissue responses to IORT. Cellular effects from radiation principally stem from direct damage to DNA, and thus proliferating tissues are among the most radiosensitive, with arrested or abnormal cell division. These tissues can manifest striking early toxicity, reflecting the rate of cell division that is affected by the radiation. Irradiation of nonproliferating or slowly proliferating tissues may show little or no early toxicity, but late effects can be manifested to considerable and varying degrees. In much of this late toxicity, pathologic changes develop from progressive ischemia, brought about by the gradual obliteration of small blood vessels. Irradiated endothelium often becomes replaced by a thickened fibrous layer, which, in small vessels, leads to occlusion and ischemic necrotic changes in the supplied tissue. In larger vessels, fibrosis can lead to wall weakening and aneurysmal dilatation, rupture, or thrombosis. The common denominator, then, of radiation damage to many tissues is related to vascular effects. Although the tolerance to IORT-induced toxicity can vary considerably among tissues, doses ranging to 25 Gy can generally be tolerated without significant toxicity. Vital areas where IORT dose must be carefully monitored include critical vasculature, gastrointestinal viscera, ureter, significant motor or sensory nerve trunks, and central nervous system structures. Higher doses can generally be delivered safely to anatomic areas at risk for tumor that are at a distance from sensitive organs or tissues. The general principle providing the rationale of IORT should always be practiced: maximize the radiation dose to the tumor and tumor-harboring tissues while minimizing dose exposure to surrounding normal tissues. JF - Surgical oncology clinics of North America AU - Sindelar, William F AU - Kinsella, Timothy J AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 925 EP - 942 VL - 12 IS - 4 SN - 1055-3207, 1055-3207 KW - Index Medicus KW - Models, Animal KW - Animals KW - Radiation Dosage KW - Combined Modality Therapy KW - Humans KW - Urinary Tract -- radiation effects KW - Dose-Response Relationship, Radiation KW - Nervous System -- radiation effects KW - Cardiovascular System -- radiation effects KW - Musculoskeletal System -- radiation effects KW - Respiratory System -- radiation effects KW - Digestive System -- radiation effects KW - Dogs KW - Surgical Procedures, Operative KW - Intraoperative Period KW - Radiotherapy, Adjuvant -- methods KW - Radiation Tolerance -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71555220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Surgical+oncology+clinics+of+North+America&rft.atitle=Normal+tissue+tolerance+to+intraoperative+radiotherapy.&rft.au=Sindelar%2C+William+F%3BKinsella%2C+Timothy+J&rft.aulast=Sindelar&rft.aufirst=William&rft.date=2003-10-01&rft.volume=12&rft.issue=4&rft.spage=925&rft.isbn=&rft.btitle=&rft.title=Surgical+oncology+clinics+of+North+America&rft.issn=10553207&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-25 N1 - Date created - 2004-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Promising directions for the diagnosis and management of gynecological cancers. AN - 71522156; 14763176 AB - Diagnosis and management of cancer requires tools with both high sensitivity and specificity. The minimally invasive cervical smear has demonstrated how a test, even one with low specificity, can change the public health profile of a cancer from a late stage deadly disease to early diagnosis with rare tumor-related deaths. The benefit of such a test is best demonstrated by the low frequency of cervix cancer and its good outcome in countries where this test is readily available and used with appropriate secondary follow up. Early and specific symptoms, and identification and prevention for high risk groups has had similar impact for endometrial cancer. Neither a robust test, nor reliable or specific early symptoms are available for ovarian cancer, making clinical and scientific advances in this area a critical world-wide need. Current approaches testing one protein or gene marker at a time will not address this crisis expeditiously. New sensitive, specific, accurate, and reliable technologies that can be implemented using high throughput mechanisms are needed at as low a cost as possible. Ideally, these technologies should be focused on readily available patient resources, such as blood or urine, or as in the case of cervix cancer, minimally invasive informative approaches such as cervical smears. Techniques that allow data mining from a large input database overcome the slow advances of one protein-one gene investigation, and further address the multi-faceted carcinogenesis process occurring even in germ line mutation-associated malignancy. Proteomics, the study of the cellular proteins and their activation states, has led the progress in biomarker development for ovarian and other cancers and is being applied to management assessment. Amenable to high throughput, internet interface, and representative of the proteome spectrum, proteomic technology is the newest and most promising direction for translational developments in gynecologic cancers. JF - International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics AU - Kohn, E C AU - Mills, G B AU - Liotta, L AD - Laboratory of Pathology, Gynecologic Malignancies Faculty, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. ek1b@nih.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 203 EP - 209 VL - 83 Suppl 1 SN - 0020-7292, 0020-7292 KW - Biomarkers, Tumor KW - 0 KW - Index Medicus KW - Humans KW - Female KW - Proteomics -- trends KW - Genital Neoplasms, Female -- therapy KW - Biomarkers, Tumor -- analysis KW - Genital Neoplasms, Female -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71522156?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+gynaecology+and+obstetrics%3A+the+official+organ+of+the+International+Federation+of+Gynaecology+and+Obstetrics&rft.atitle=Promising+directions+for+the+diagnosis+and+management+of+gynecological+cancers.&rft.au=Kohn%2C+E+C%3BMills%2C+G+B%3BLiotta%2C+L&rft.aulast=Kohn&rft.aufirst=E&rft.date=2003-10-01&rft.volume=83+Suppl+1&rft.issue=&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=International+journal+of+gynaecology+and+obstetrics%3A+the+official+organ+of+the+International+Federation+of+Gynaecology+and+Obstetrics&rft.issn=00207292&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-20 N1 - Date created - 2004-02-06 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Patient and program factors in obtaining supportive services in DATOS. AN - 71462987; 14670522 AB - This study examined patient and program factors that influenced the receipt of scheduled supportive services in the Drug Abuse Treatment Outcome Studies (DATOS). Patients (N = 2,932) in 21 long-term residential (LTR) programs, 27 outpatient methadone treatment (OMT), and 25 outpatient drug-free programs were interviewed at admission and at 3 months during treatment. A hierarchical regression analysis was used to examine the relationship between patient-level and program-level factors associated with receiving supportive services in seven categories (medical, psychological, family, legal, educational, vocational, and financial). LTR patients received more services on average than outpatients (especially OMT), but patients overall received few services in the first 3 months of treatment. The patient-level likelihood of receiving services was related to being female and to having higher problem severity at intake. At the program level, outpatient clientele with higher problem severity received more services if they entered a program whose other enrolled patients were less troubled on average. JF - Journal of substance abuse treatment AU - Fletcher, Bennett W AU - Broome, Kirk M AU - Delany, Peter J AU - Shields, Joseph AU - Flynn, Patrick M AD - National Institute on Drug Abuse National Institutes of Health, 6001 Executive Boulevard, Room 5159, Bethesda, MD 20892, USA. bennet_fletcher@nih.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 165 EP - 175 VL - 25 IS - 3 SN - 0740-5472, 0740-5472 KW - Index Medicus KW - United States KW - Referral and Consultation -- statistics & numerical data KW - Sex Factors KW - Combined Modality Therapy KW - Humans KW - Ambulatory Care -- utilization KW - Substance Abuse Treatment Centers -- utilization KW - Eligibility Determination -- statistics & numerical data KW - Likelihood Functions KW - Comorbidity KW - Length of Stay -- statistics & numerical data KW - Adult KW - Patient Admission -- statistics & numerical data KW - Follow-Up Studies KW - Female KW - Male KW - Heroin Dependence -- epidemiology KW - Patient Care Team -- utilization KW - Patient Acceptance of Health Care -- statistics & numerical data KW - Cocaine-Related Disorders -- psychology KW - Outcome Assessment (Health Care) -- statistics & numerical data KW - Heroin Dependence -- rehabilitation KW - Social Support KW - Cocaine-Related Disorders -- epidemiology KW - Heroin Dependence -- psychology KW - Cocaine-Related Disorders -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71462987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse+treatment&rft.atitle=Patient+and+program+factors+in+obtaining+supportive+services+in+DATOS.&rft.au=Fletcher%2C+Bennett+W%3BBroome%2C+Kirk+M%3BDelany%2C+Peter+J%3BShields%2C+Joseph%3BFlynn%2C+Patrick+M&rft.aulast=Fletcher&rft.aufirst=Bennett&rft.date=2003-10-01&rft.volume=25&rft.issue=3&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse+treatment&rft.issn=07405472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-19 N1 - Date created - 2003-12-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intracellular localization is a cofactor for the phototoxicity of protoporphyrin IX in the gastrointestinal tract: in vitro study. AN - 71395124; 14626668 AB - Photodynamic therapy (PDT) is a new treatment modality for solid tumors as well as for flat lesions of the gastrointestinal tract. Although the use of 5-aminolevulinic acid-induced protoporphyrin IX (PPIX) shows important advantages over other photosensitizers, the main mechanisms of phototoxicity induced are still poorly understood. Three human colon carcinoma cell lines with variable degrees of differentiation and a normal colon fibroblast cell line were used to generate a suitable in vitro model for investigation of photosensitizer concentration as well as the applied light dose. Also, the effects of intracellular photosensitizer localization on efficiency of PDT were examined, and cellular parameters after PDT (morphology, mitochondrial transmembrane potential, membrane integrity and DNA fragmentation) were analyzed to distinguish between PDT-induced apoptosis from necrosis. The fibroblast cell line was less affected by phototoxicity than the tumor cells to a variable degree. Well-differentiated tumor cells showed higher toxicity than less-differentiated cells. After irradiation, cell lines with cytosolic or mitochondrial PPIX localization indicate a loss of mitochondrial transmembrane potential resulting in growth arrest, whereas membrane-bound PPIX induces a loss of membrane integrity and consequent necrosis. Although the absolute amount of intracellular photosensitizer concentration plays the main determining role for PDT efficiency, data indicate that intracellular localization has additional effects on the mode of cell damage. JF - Photochemistry and photobiology AU - Krieg, René C AU - Messmann, Helmut AU - Schlottmann, Klaus AU - Endlicher, Esther AU - Seeger, Stephan AU - Schölmerich, Jürgen AU - Knuechel, Ruth AD - National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 393 EP - 399 VL - 78 IS - 4 SN - 0031-8655, 0031-8655 KW - Photosensitizing Agents KW - 0 KW - Protoporphyrins KW - protoporphyrin IX KW - C2K325S808 KW - Index Medicus KW - Tumor Cells, Cultured KW - Photochemotherapy -- adverse effects KW - Humans KW - Colonic Neoplasms -- drug therapy KW - Adenocarcinoma -- drug therapy KW - Photosensitizing Agents -- adverse effects KW - Digestive System -- drug effects KW - Protoporphyrins -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71395124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Photochemistry+and+photobiology&rft.atitle=Intracellular+localization+is+a+cofactor+for+the+phototoxicity+of+protoporphyrin+IX+in+the+gastrointestinal+tract%3A+in+vitro+study.&rft.au=Krieg%2C+Ren%C3%A9+C%3BMessmann%2C+Helmut%3BSchlottmann%2C+Klaus%3BEndlicher%2C+Esther%3BSeeger%2C+Stephan%3BSch%C3%B6lmerich%2C+J%C3%BCrgen%3BKnuechel%2C+Ruth&rft.aulast=Krieg&rft.aufirst=Ren%C3%A9&rft.date=2003-10-01&rft.volume=78&rft.issue=4&rft.spage=393&rft.isbn=&rft.btitle=&rft.title=Photochemistry+and+photobiology&rft.issn=00318655&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-02 N1 - Date created - 2003-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ongoing adjuvant trials with trastuzumab in breast cancer. AN - 71363108; 14613027 AB - Trastuzumab has had a major impact in the treatment of HER2-positive metastatic breast cancer. In combination with chemotherapy, trastuzumab provides significant clinical benefit in terms of increased response rate and extended survival compared with chemotherapy alone in patients with HER2-positive advanced breast cancer. Trastuzumab also has therapeutic activity as monotherapy in the front-line management of HER2-overexpressed or HER2-amplified metastatic breast cancer. Given its proven efficacy in the metastatic setting, the combination and sequential use of trastuzumab with adjuvant and neoadjuvant chemotherapy are the focus of several ongoing clinical studies. In this review, the design of the four major phase III multicenter adjuvant trastuzumab trials will be described and their major differences highlighted. Because therapy with trastuzumab has been associated with cardiac toxicity, especially with prior or concurrent anthracyclines, the evaluation of cardiac dysfunction in the adjuvant trial setting is also a priority. For now, the use of trastuzumab as adjuvant therapy is still investigational, but its integration has tremendous potential to improve treatment outcomes in patients with primary breast cancer. JF - Seminars in oncology AU - Tan, Antoinette R AU - Swain, Sandra M AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20889, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 54 EP - 64 VL - 30 IS - 5 Suppl 16 SN - 0093-7754, 0093-7754 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Humanized KW - Antineoplastic Agents KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Trastuzumab KW - P188ANX8CK KW - Index Medicus KW - Receptor, ErbB-2 -- metabolism KW - Clinical Trials, Phase III as Topic KW - Humans KW - Neoadjuvant Therapy KW - Chemotherapy, Adjuvant KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- metabolism KW - Antibodies, Monoclonal -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- adverse effects KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71363108?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ongoing+adjuvant+trials+with+trastuzumab+in+breast+cancer.&rft.au=Tan%2C+Antoinette+R%3BSwain%2C+Sandra+M&rft.aulast=Tan&rft.aufirst=Antoinette&rft.date=2003-10-01&rft.volume=30&rft.issue=5+Suppl+16&rft.spage=54&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 - 2003-12-12 N1 - Date created - 2003-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cozart RapiScan Oral Fluid Drug Testing System: an evaluation of sensitivity, specificity, and efficiency for cocaine detection compared with ELISA and GC-MS following controlled cocaine administration. AN - 71357815; 14606993 AB - Oral fluid has become a widely accepted alternative matrix for drugs of abuse detection. Immunoassays have been developed for on-site testing of cocaine and metabolites in oral fluid. The performance of the Cozart RapiScan Oral Fluid Drug Testing System (CRS) was evaluated in comparison with Cozart Microplate Enzyme Immunoassay Cocaine Oral Fluid Kit (COC ELISA) and gas chromatography-mass spectrometry (GC-MS) at several screening and confirmation cutoffs, including those proposed by SAMHSA and those currently in use in the U.K. Oral fluid samples (n = 1271) were collected prior to and following controlled clinical cocaine administration. CRS provides a qualitative screen at a preset cutoff of 30 microg/L. Sensitivity, specificity, and efficiency for CRS (30 microg/L) as compared with COC ELISA with a cutoff of 30 microg/L were 92.1%, 91.8%, and 92.0%. The comparison of CRS (30 microg/L) with the 8-mg/L proposed SAMHSA confirmation cutoffs for cocaine and/or benzoylecgonine exhibited a sensitivity of 82.7%, a specificity of 94.5%, and an efficiency of 87.6%. For this study, an alternative CRS cutoff of 20 microg/L was also evaluated. Performance characteristics of CRS (20 microg/L) at the proposed SAMHSA confirmation cutoffs were 89.9%, 89.7%, and 89.8%, respectively. At cutoffs in use in the U.K., 30- micro g/L CRS screen and 15- microg/L GC-MS cutoffs for cocaine, benzoylecgonine, and/or ecgonine methyl ester sensitivity, specificity, and efficiency were 89.4%, 92.2%, and 90.7%, respectively. Cozart RapiScan had performance similar to the COC ELISA assay for the detection of cocaine exposure and suitable sensitivity and specificity at the proposed SAMHSA cutoffs. JF - Journal of analytical toxicology AU - Kolbrich, Erin A AU - Kim, Insook AU - Barnes, Allan J AU - Moolchan, Eric T AU - Wilson, Lisa AU - Cooper, Gail A AU - Reid, Claire AU - Baldwin, Dene AU - Hand, Chris W AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 407 EP - 411 VL - 27 IS - 7 SN - 0146-4760, 0146-4760 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Sensitivity and Specificity KW - Humans KW - Gas Chromatography-Mass Spectrometry KW - Enzyme-Linked Immunosorbent Assay KW - Cocaine-Related Disorders -- diagnosis KW - Cocaine -- analysis KW - Saliva -- chemistry KW - Cocaine -- pharmacokinetics KW - Cocaine -- administration & dosage KW - Substance Abuse Detection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71357815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cozart+RapiScan+Oral+Fluid+Drug+Testing+System%3A+an+evaluation+of+sensitivity%2C+specificity%2C+and+efficiency+for+cocaine+detection+compared+with+ELISA+and+GC-MS+following+controlled+cocaine+administration.&rft.au=Kolbrich%2C+Erin+A%3BKim%2C+Insook%3BBarnes%2C+Allan+J%3BMoolchan%2C+Eric+T%3BWilson%2C+Lisa%3BCooper%2C+Gail+A%3BReid%2C+Claire%3BBaldwin%2C+Dene%3BHand%2C+Chris+W%3BHuestis%2C+Marilyn+A&rft.aulast=Kolbrich&rft.aufirst=Erin&rft.date=2003-10-01&rft.volume=27&rft.issue=7&rft.spage=407&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 - 2004-07-16 N1 - Date created - 2003-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sensitivity, specificity, and efficiency in detecting opiates in oral fluid with the Cozart Opiate Microplate EIA and GC-MS following controlled codeine administration. AN - 71346877; 14606992 AB - Oral fluid specimens (N = 1406) were collected from 19 subjects prior to and up to 72 h following controlled administration of oral codeine. Volunteers provided informed consent to participate in this National Institute on Drug Abuse Institutional Review Board-approved protocol. A modification of Cozart Microplate Opiate EIA Oral Fluid Kit (Opiate ELISA), employing codeine calibrators, was used for semiquantitative analysis of opiates, followed by gas chromatography-mass spectrometry (GC-MS) for the confirmation and quantitation of codeine, norcodeine, morphine, and normorphine in oral fluid. GC-MS limits of detection and quantitation were 2.5 microg/L for all analytes. The Substance Abuse and Mental Health Services Administration (SAMHSA) has proposed a 40-microg/L opiate screening and a 40-microg/L morphine or codeine confirmation cutoff for the detection of opiate use. Oral fluid opiate screening and confirmation cutoffs of 30 micro g/L are in use in the U.K. Utilizing 2.5-, 20-, 30-, and 40-microg/L GC-MS cutoffs, 26%, 20%, 19%, and 18% of the oral fluid specimens were positive for codeine or one of its metabolites. Six Opiate ELISA/confirmation cutoff criteria (2.5/2.5, 10/2.5, 20/20, 30/20, 30/30, and 40/40 microg/L) were evaluated. Calculations for Opiate ELISA sensitivity, specificity, and efficiency were determined from the number of true-positive, true-negative, false-positive, and false-negative results at each screening/confirmation cutoff. Sensitivity, specificity, and efficiency for the lowest cutoff were 91.5%, 88.6%, and 89.3%. Application of the cutoff currently used in the U.K. yielded sensitivity, specificity, and efficiency results of 79.7%, 99.0%, and 95.4% and similar results of 76.7%, 99.1%, and 95.1% when applying the SAMHSA criteria. These data indicate that the Opiate ELISA efficiently detects oral codeine use. In addition, the data, collected following controlled oral codeine administration, may aid in the interpretation of opiate oral fluid test results and in the selection of appropriate oral fluid screening and confirmation cutoffs. JF - Journal of analytical toxicology AU - Barnes, Allan J AU - Kim, Insook AU - Schepers, Raf AU - Moolchan, Eric T AU - Wilson, Lisa AU - Cooper, Gail AU - Reid, Claire AU - Hand, Chris AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21124, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 402 EP - 407 VL - 27 IS - 7 SN - 0146-4760, 0146-4760 KW - Codeine KW - Q830PW7520 KW - Index Medicus KW - Sensitivity and Specificity KW - Administration, Oral KW - Humans KW - Gas Chromatography-Mass Spectrometry KW - Enzyme-Linked Immunosorbent Assay KW - Male KW - Female KW - Opioid-Related Disorders -- diagnosis KW - Codeine -- analysis KW - Codeine -- administration & dosage KW - Saliva -- chemistry KW - Codeine -- pharmacokinetics KW - Substance Abuse Detection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71346877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sensitivity%2C+specificity%2C+and+efficiency+in+detecting+opiates+in+oral+fluid+with+the+Cozart+Opiate+Microplate+EIA+and+GC-MS+following+controlled+codeine+administration.&rft.au=Barnes%2C+Allan+J%3BKim%2C+Insook%3BSchepers%2C+Raf%3BMoolchan%2C+Eric+T%3BWilson%2C+Lisa%3BCooper%2C+Gail%3BReid%2C+Claire%3BHand%2C+Chris%3BHuestis%2C+Marilyn+A&rft.aulast=Barnes&rft.aufirst=Allan&rft.date=2003-10-01&rft.volume=27&rft.issue=7&rft.spage=402&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 - 2004-07-16 N1 - Date created - 2003-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bioassay-guided isolation of epiquinamide, a novel quinolizidine alkaloid and nicotinic agonist from an Ecuadoran poison frog, Epipedobates tricolor. AN - 71309454; 14575435 AB - Analytical HPLC fractionation, combined with an off-line 96-well fluorescent bioassay screen, has been developed and used for the separation and screening of a natural product extract. This method was used to guide the isolation of a novel quinolizidine alkaloid from the methanolic skin extracts of an Ecuadoran frog, Epipedobates tricolor. The structure was determined on the basis of MS, IR, and NMR analysis as (1R,10R)-1-acetamidoquinolizidine (alkaloid 196). We have named this compound epiquinamide, reflecting its origin and structure. The activity of the isolated compound was determined in five cell lines expressing various nicotinic acetylcholine receptor subtypes. The bioactivity of epiquinamide was evaluated on the basis of membrane potential fluorescence and was found to be beta2 selective. This compound represents a new structural class of nicotinic agonists and a potential lead compound for the development of new therapeutics and pharmacological probes for nicotinic receptors. The off-line screening technique was found to be very sensitive for the detection of compounds active at nicotinic receptors. JF - Journal of natural products AU - Fitch, Richard W AU - Garraffo, H Martin AU - Spande, Thomas F AU - Yeh, Herman J C AU - Daly, John W AD - Section on Pharmacodynamics, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 1345 EP - 1350 VL - 66 IS - 10 SN - 0163-3864, 0163-3864 KW - Alkaloids KW - 0 KW - Nicotinic Agonists KW - Quinolizines KW - Receptors, Nicotinic KW - epiquinamide KW - Index Medicus KW - Molecular Structure KW - Animals KW - Ecuador KW - Nuclear Magnetic Resonance, Biomolecular KW - Chromatography, High Pressure Liquid KW - Quinolizines -- chemistry KW - Ranidae -- metabolism KW - Alkaloids -- chemistry KW - Nicotinic Agonists -- isolation & purification KW - Skin -- secretion KW - Receptors, Nicotinic -- metabolism KW - Quinolizines -- pharmacology KW - Quinolizines -- isolation & purification KW - Alkaloids -- pharmacology KW - Alkaloids -- isolation & purification KW - Nicotinic Agonists -- pharmacology KW - Nicotinic Agonists -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71309454?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+natural+products&rft.atitle=Bioassay-guided+isolation+of+epiquinamide%2C+a+novel+quinolizidine+alkaloid+and+nicotinic+agonist+from+an+Ecuadoran+poison+frog%2C+Epipedobates+tricolor.&rft.au=Fitch%2C+Richard+W%3BGarraffo%2C+H+Martin%3BSpande%2C+Thomas+F%3BYeh%2C+Herman+J+C%3BDaly%2C+John+W&rft.aulast=Fitch&rft.aufirst=Richard&rft.date=2003-10-01&rft.volume=66&rft.issue=10&rft.spage=1345&rft.isbn=&rft.btitle=&rft.title=Journal+of+natural+products&rft.issn=01633864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-11 N1 - Date created - 2003-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel cell-based system for the rapid quantitative evaluation of (anti)-inflammatory potential of test substances. AN - 71306697; 14580881 AB - The control of NF-kappaB activation is a proven therapeutic strategy in the treatment of multiple inflammatory disorders. Drug discovery and development for such a therapy demands a battery of assays to reliably demonstrate both clinical effectiveness and biological safety of prospective medications. Unlike traditional in vitro biochemical analyses, cell-based assays more closely mimic the actual in vivo physiologic environment, addressing simultaneously biological activity and toxicity issues. A novel assay system, based solely on the drug resistance of a genetically engineered cell line, has been developed to provide rapid quantitative evaluation of the (anti)-inflammatory potential of test substances. The assay principle is based on the ability of bona fide inflammatory agents to activate the transcription factor NF-kappaB in cultured cells. In our model, expression of a dual drug resistance marker, driven by an NF-kappaB-dependent minimal promoter, provides a selective and highly sensitive scheme with a quantitative readout to detect biochemical agents with pro-or anti-inflammatory properties. The novel cell-based system is inexpensive, simple to perform (requiring only basic cell culture skills), accurate, and provides sensitivity comparable to that of the electrophoretic mobility shift assay and quantitative ELISA. In addition, the dual selection capability of the model provides a powerful tool to discover novel molecular components of the NF-kappaB signal transduction pathway. JF - Journal of immunological methods AU - Kozlov, Serguei V AU - Dobrovolskaia, Marina A AU - Rice, Nancy R AU - Stewart, Colin L AU - Vogel, Stefanie N AD - Cancer and Developmental Biology Laboratory, National Cancer Institute, P.O. Box B, Building 539, Frederick, MD 21702, USA. skozlov@ncifcrf.gov Y1 - 2003/10/01/ PY - 2003 DA - 2003 Oct 01 SP - 51 EP - 63 VL - 281 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Anti-Inflammatory Agents KW - 0 KW - Lipopolysaccharides KW - NF-kappa B KW - Tumor Necrosis Factor-alpha KW - Puromycin KW - 4A6ZS6Q2CL KW - Index Medicus KW - Signal Transduction -- physiology KW - HeLa Cells KW - Lipopolysaccharides -- pharmacology KW - Humans KW - Signal Transduction -- drug effects KW - Puromycin -- pharmacology KW - Retroviridae -- genetics KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Inflammation -- chemically induced KW - Tumor Necrosis Factor-alpha -- analysis KW - NF-kappa B -- physiology KW - Anti-Inflammatory Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71306697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunological+methods&rft.atitle=A+novel+cell-based+system+for+the+rapid+quantitative+evaluation+of+%28anti%29-inflammatory+potential+of+test+substances.&rft.au=Kozlov%2C+Serguei+V%3BDobrovolskaia%2C+Marina+A%3BRice%2C+Nancy+R%3BStewart%2C+Colin+L%3BVogel%2C+Stefanie+N&rft.aulast=Kozlov&rft.aufirst=Serguei&rft.date=2003-10-01&rft.volume=281&rft.issue=1-2&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunological+methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-10 N1 - Date created - 2003-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis, characterization and biological properties of a novel copper complex. AN - 71301326; 14575936 AB - The study of copper complex in relation to cancer is important in many ways. A novel copper complex has been synthesized with non toxic ligand, viz. potassium salt of N-(2-hydroxy acetophenone) glycinate (NHAG). The structure of the complex has been determined by spectroscopic means. Toxicity and antitumor property of the complex has been studied in vivo. Though the complex is toxic at higher doses, lower non toxic doses of the complex deplete glutathione (GSH). GSH depleting property of the complex may be utilized to sensitize drug resistant cells where resistance is due to elevated level of GSH. JF - European journal of medicinal chemistry AU - Majumder, Surajit AU - Panda, Gouri Sankar AU - Kumar Choudhuri, Soumitra AD - Department of Environmental Carcinogenesis and Toxicology (ECT), Chittaranjan National Cancer Institute (CNCI), 37 S.P. Mukherjee Road, Calcutta 700 026, India. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 893 EP - 898 VL - 38 IS - 10 SN - 0223-5234, 0223-5234 KW - Antineoplastic Agents KW - 0 KW - Ligands KW - Organometallic Compounds KW - Copper KW - 789U1901C5 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Bone Marrow Cells -- drug effects KW - Animals KW - Spleen -- cytology KW - Dose-Response Relationship, Drug KW - Glutathione -- metabolism KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Drug Resistance, Neoplasm KW - Mice KW - Blood Cell Count KW - Survival Rate KW - Cell Survival -- drug effects KW - Spleen -- drug effects KW - Drug Evaluation, Preclinical KW - Male KW - Antineoplastic Agents -- toxicity KW - Antineoplastic Agents -- chemical synthesis KW - Organometallic Compounds -- toxicity KW - Organometallic Compounds -- therapeutic use KW - Organometallic Compounds -- chemical synthesis KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71301326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+medicinal+chemistry&rft.atitle=Synthesis%2C+characterization+and+biological+properties+of+a+novel+copper+complex.&rft.au=Majumder%2C+Surajit%3BPanda%2C+Gouri+Sankar%3BKumar+Choudhuri%2C+Soumitra&rft.aulast=Majumder&rft.aufirst=Surajit&rft.date=2003-10-01&rft.volume=38&rft.issue=10&rft.spage=893&rft.isbn=&rft.btitle=&rft.title=European+journal+of+medicinal+chemistry&rft.issn=02235234&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-08 N1 - Date created - 2003-10-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tobacco Craving Questionnaire: reliability and validity of a new multifactorial instrument. AN - 71299486; 14577981 AB - This study documented the initial reliability and validity of the Tobacco Craving Questionnaire (TCQ), a new multidimensional questionnaire to assess tobacco craving. Current cigarette smokers (n=213) not attempting to reduce or quit smoking completed the 47-item TCQ and other forms assessing demographics, tobacco and other drug use history, quit attempts, and current mood. Exploratory factor analyses and structural equation modeling indicated that a four-factor solution best described the item structure. Factor subscales derived from the 17 items with significant loadings had low to high internal consistencies and interitem correlations and exhibited low to moderate, positive intercorrelations. Factor scales were significantly correlated with single-item measures of craving, current mood, and daily cigarette smoking. Results indicated that four specific constructs characterized craving for tobacco: (a) Emotionality, or smoking in anticipation of relief from withdrawal symptoms or negative mood, (b) expectancy, or anticipation of positive outcomes from smoking, (c) compulsivity, or an inability to control tobacco use, and (d) purposefulness, or intention and planning to smoke for positive outcomes. These preliminary data suggest that the TCQ is a reliable and valid instrument for assessing tobacco craving in individuals not attempting to reduce or quit smoking. JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Heishman, Stephen J AU - Singleton, Edward G AU - Moolchan, Eric T AD - Clinical Pharmacology and Therapeutics Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore MD 21224, USA. heishman@nih.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 645 EP - 654 VL - 5 IS - 5 SN - 1462-2203, 1462-2203 KW - Ganglionic Stimulants KW - 0 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Sensitivity and Specificity KW - Reproducibility of Results KW - Ganglionic Stimulants -- pharmacology KW - Nicotine -- pharmacology KW - Humans KW - Smoking Cessation KW - Adult KW - Affect KW - Male KW - Female KW - Surveys and Questionnaires KW - Tobacco Use Disorder -- psychology KW - Tobacco Use Disorder -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71299486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.atitle=Tobacco+Craving+Questionnaire%3A+reliability+and+validity+of+a+new+multifactorial+instrument.&rft.au=Heishman%2C+Stephen+J%3BSingleton%2C+Edward+G%3BMoolchan%2C+Eric+T&rft.aulast=Heishman&rft.aufirst=Stephen&rft.date=2003-10-01&rft.volume=5&rft.issue=5&rft.spage=645&rft.isbn=&rft.btitle=&rft.title=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.issn=14622203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-10 N1 - Date created - 2003-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smoking topography: reliability and validity in dependent smokers. AN - 71296856; 14577984 AB - Data from two studies were analyzed to determine whether smoking through the mouthpiece of a topography unit yields consistent measures over time and to verify that smoking through a mouthpiece results in a similar degree of smoke exposure as conventional smoking. In both studies, subjects smoked their usual brand of cigarette ad libitum. In study A, subjects (n=7) smoked through a mouthpiece on 4 separate experimental days. In study B, subjects (n=10) smoked on 2 separate days: Once conventionally and once through a mouthpiece. In both studies, exhaled carbon monoxide (CO) and physiological effects (heart rate and blood pressure) were measured before and after smoking. In study B, plasma nicotine concentrations also were measured. In study A, puff volume, puff duration, interpuff interval, and maximum puff velocity averaged 30.8 ml,.9 s, 19.9 s, and 44.6 ml/s, respectively. Intraclass correlation coefficients computed for puff volume (0.66), puff duration (0.75), and maximum puff velocity (0.68) indicated that these measures showed good reliability. In study B, smoking through the mouthpiece yielded similar topographical (time to smoke and number of puffs per cigarette) measures as conventional smoking. Also similar were changes in biochemical values: Plasma nicotine (18.5 ng/ml vs. 25.5 ng/ml), exhaled CO (4.6 ppm vs. 5.1 ppm), and heart rate (8.6 beats/min vs. 7.4 beats/min) for conventional and topography mouthpiece smoking conditions, respectively. Topography measures did not differ significantly between the two studies. Overall, the data from these two small-sample studies suggest that smoking topography provides a valid and reliable index of conventional smoking and an indirect measure of smoke exposure. JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Lee, Eun M AU - Malson, Jennifer L AU - Waters, Andrew J AU - Moolchan, Eric T AU - Pickworth, Wallace B AD - National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore MD 21224, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 673 EP - 679 VL - 5 IS - 5 SN - 1462-2203, 1462-2203 KW - Carbon Monoxide KW - 7U1EE4V452 KW - Index Medicus KW - Sensitivity and Specificity KW - Heart Rate KW - Equipment Design KW - Carbon Monoxide -- analysis KW - Reproducibility of Results KW - Blood Pressure KW - Humans KW - Adult KW - Male KW - Female KW - Smoking KW - Tobacco Use Disorder KW - Models, Theoretical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71296856?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.atitle=Smoking+topography%3A+reliability+and+validity+in+dependent+smokers.&rft.au=Lee%2C+Eun+M%3BMalson%2C+Jennifer+L%3BWaters%2C+Andrew+J%3BMoolchan%2C+Eric+T%3BPickworth%2C+Wallace+B&rft.aulast=Lee&rft.aufirst=Eun&rft.date=2003-10-01&rft.volume=5&rft.issue=5&rft.spage=673&rft.isbn=&rft.btitle=&rft.title=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.issn=14622203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-10 N1 - Date created - 2003-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recommendations on use of biomarkers in alcoholism treatment trials. AN - 71293221; 14574239 AB - Biochemical markers of heavy drinking are playing increasingly prominent roles in alcohol treatment efficacy studies, especially in those designed to evaluate medications. Among these roles are serving as inclusion or exclusion criteria for research participants, corroboration of self-report of drinking status, assessment of the safety of the agent being evaluated, and determination of treatment outcome. Recent alcohol medication development trials that included biomarker information were reviewed and critiqued from the perspectives of how biomarker measures were used and how findings on them were reported. Although generally the application of biomarkers as inclusion criteria is not recommended, they may aid in exclusion of potential subjects (e.g., elevated liver function measures in trials of agents that could result in liver damage). Biomarkers are most commonly used as indicators of outcome, usually serving as secondary outcome variables. The relationship of outcome findings on biomarker and self-report measures is positive, but only moderate. As used to date, biomarkers of drinking tend to be less sensitive than well-standardized and properly administered self-report measures. Nevertheless, they do provide a useful, unique source of information on drinking status. The contribution of biomarkers to alcoholism clinical research would be enhanced if certain design strategies were incorporated into their application and if critical information were included in the research publication. This article offers a series of recommendations to improve on their use in a research context. JF - Alcoholism, clinical and experimental research AU - Allen, John P AU - Litten, Raye Z AD - National Institute on Alcohol Abuse and Alcoholism, Vienna, Virginia, USA. jpallenphd@cs.com Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 1667 EP - 1670 VL - 27 IS - 10 SN - 0145-6008, 0145-6008 KW - Biomarkers KW - 0 KW - Index Medicus KW - Humans KW - Biomarkers -- analysis KW - Health Planning Guidelines KW - Treatment Outcome KW - Alcoholism -- therapy KW - Alcoholism -- metabolism KW - Clinical Trials as Topic -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71293221?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recommendations+on+use+of+biomarkers+in+alcoholism+treatment+trials.&rft.au=Allen%2C+John+P%3BLitten%2C+Raye+Z&rft.aulast=Allen&rft.aufirst=John&rft.date=2003-10-01&rft.volume=27&rft.issue=10&rft.spage=1667&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 - 2004-06-15 N1 - Date created - 2003-10-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective opening of the blood-tumor barrier by a nitric oxide donor and long-term survival in rats with C6 gliomas. AN - 71284430; 14567609 AB - The response of brain tumors to systemic chemotherapy is limited by the blood-tumor barrier (BTB). Nitric oxide (NO) has been implicated in the regulation of vascular permeability and blood flow. The authors evaluated the effects of exogenous NO, which was released from a short-acting NO donor (Proli/NO), and those of NO metabolites on the capillary permeability of tumors and normal brain tissue by using quantitative autoradiography in a C6 glioma model in rats. The Proli/NO was infused at a wide dose range (10(-2) to 10(-12) M) either intravenously or into the internal carotid artery (ICA) and demonstrated substantial tumor-selective increases in blood-brain barrier (BBB) permeability in response to various-sized tracers ([14C]aminoisobutyric acid, [14C]sucrose, [14C]dextran). Internal carotid artery or intravenous administration of sodium nitrite had a comparable effect on BTB permeability. The NO effect on microvascular permeability could be obtained without causing hemodynamic side effects. The effect of NO on the efficacy of carboplatin chemotherapy was investigated in intracerebral C6 gliomas. Simultaneous intravenous infusions of Proli/NO (10(-6) M) and carboplatin (20 mg/kg) led to long-term survival in 40% of rats harboring intracerebral C6 gliomas compared with control animals receiving ICA or intravenous infusions of carboplatin, Proli/NO, or vehicle alone. No residual tumor was demonstrated on histological or magnetic resonance imaging studies performed in rats treated with Proli/NO and carboplatin, and no toxicity was observed. This new approach demonstrated the in vivo efficacy and safety of NO and nitrite in enhancing the delivery of systemically delivered radiolabeled tracers and carboplatin into rat gliomas. The NO-induced tumor-selective BBB disruption and intravenous carboplatin chemotherapy may be more efficacious than current chemotherapy strategies against brain tumors. JF - Journal of neurosurgery AU - Weyerbrock, Astrid AU - Walbridge, Stuart AU - Pluta, Ryszard M AU - Saavedra, Joseph E AU - Keefer, Larry K AU - Oldfield, Edward H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 728 EP - 737 VL - 99 IS - 4 SN - 0022-3085, 0022-3085 KW - Antineoplastic Agents KW - 0 KW - Nitric Oxide Donors KW - Nitrogen Oxides KW - proline-nitric oxide KW - Nitric Oxide KW - 31C4KY9ESH KW - Proline KW - 9DLQ4CIU6V KW - Carboplatin KW - BG3F62OND5 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Antineoplastic Agents -- administration & dosage KW - Injections, Intravenous KW - Injections, Intra-Arterial KW - Disease Models, Animal KW - Capillary Permeability -- drug effects KW - Carboplatin -- therapeutic use KW - Carboplatin -- administration & dosage KW - Rats KW - Blood KW - Rats, Sprague-Dawley KW - Survival Rate KW - Carotid Artery, Internal KW - Antineoplastic Agents -- therapeutic use KW - Time Factors KW - Male KW - Brain Neoplasms -- mortality KW - Nitric Oxide Donors -- administration & dosage KW - Blood-Brain Barrier -- physiology KW - Brain Neoplasms -- blood supply KW - Glioma -- mortality KW - Nitric Oxide -- administration & dosage KW - Glioma -- blood supply KW - Nitric Oxide Donors -- pharmacokinetics KW - Brain Neoplasms -- drug therapy KW - Glioma -- drug therapy KW - Nitric Oxide Donors -- therapeutic use KW - Nitric Oxide -- pharmacokinetics KW - Proline -- administration & dosage KW - Proline -- pharmacokinetics KW - Proline -- therapeutic use KW - Nitric Oxide -- therapeutic use KW - Proline -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71284430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurosurgery&rft.atitle=Selective+opening+of+the+blood-tumor+barrier+by+a+nitric+oxide+donor+and+long-term+survival+in+rats+with+C6+gliomas.&rft.au=Weyerbrock%2C+Astrid%3BWalbridge%2C+Stuart%3BPluta%2C+Ryszard+M%3BSaavedra%2C+Joseph+E%3BKeefer%2C+Larry+K%3BOldfield%2C+Edward+H&rft.aulast=Weyerbrock&rft.aufirst=Astrid&rft.date=2003-10-01&rft.volume=99&rft.issue=4&rft.spage=728&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-17 N1 - Date created - 2003-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors Involved in the Pharmacokinetics of COL-3, a Matrix Metalloproteinase Inhibitor, in Patients with Refractory Metastatic Cancer: Clinical and Experimental Studies AN - 21206677; 11643967 AB - COL-3 is an oral, lipophilic, tetracycline analog that has been administered to patients with metastatic cancer. Preliminary assessment of COL-3 in 35 patients with refractory metastatic carcinoma demonstrated apparent nonlinear pharmacokinetics with highly variable oral clearance (63.9% coefficient of variance [CV]). To elucidate possible sources of variability of COL-3 pharmacokinetics in vivo, in vitro plasma protein binding and in vitro metabolism were explored along with in vivo pharmacokinetics using compartmental modeling. The variability in the overall clearance and urinary excretion of COL-3 was also assessed. COL-3 had a long terminal half-life (median = 59.8 h), large apparent volume of distribution (median = 50.2 L), and low apparent clearance (median = 9.93 mL/min). Only adjusted ideal body weight de-creased the variability in total apparent clearance. There was nonsaturable plasma protein binding of COL-3 (f sub(u) = 5.5%), with the majority of binding to albumin. The renal route of elimination is negligible, with 0.06% of unchanged COL-3 and 3.31% COL-3 glucuronide excreted in the first 6 days. COL-3 is not metabolized by phase I metabolism but does undergo glucuronidation in vitro by UGT1A1, UGT1A3, UGT1A9, and UGT2B7 and in vivo, as evidenced by COL-3 glucuronides in the urine (median = 13.6% of the total dose). COL-3 exhibits nonlinear pharmacokinetics, possibly due to dissolution rate-limited absorption. JF - Journal of Clinical Pharmacology AU - Rudek, Michelle A AU - Venitz, Juergen AU - Ando, Yuichi AU - Reed, Eddie AU - Pluda, James M AU - Figg, William D AD - Clinical Pharmacology Research Core, Medical Oncology Clinical Research Unit, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, Department of Pharmaceutics, School of Pharmacy, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, Virginia Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 1124 EP - 1135 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 43 IS - 10 SN - 0091-2700, 0091-2700 KW - Toxicology Abstracts KW - COL-3 KW - metastatic cancer KW - pharmacokinetics KW - metabolism KW - Matrix metalloproteinase KW - Tetracyclines KW - Lipophilic KW - Pharmacokinetics KW - Carcinoma KW - Plasma proteins KW - Metastases KW - Body weight KW - Urine KW - Albumin KW - Kidney KW - Dissolution KW - Protein turnover KW - Excretion KW - Metabolism KW - X 24360:Metals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21206677?accountid=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+Clinical+Pharmacology&rft.atitle=Factors+Involved+in+the+Pharmacokinetics+of+COL-3%2C+a+Matrix+Metalloproteinase+Inhibitor%2C+in+Patients+with+Refractory+Metastatic+Cancer%3A+Clinical+and+Experimental+Studies&rft.au=Rudek%2C+Michelle+A%3BVenitz%2C+Juergen%3BAndo%2C+Yuichi%3BReed%2C+Eddie%3BPluda%2C+James+M%3BFigg%2C+William+D&rft.aulast=Rudek&rft.aufirst=Michelle&rft.date=2003-10-01&rft.volume=43&rft.issue=10&rft.spage=1124&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Pharmacology&rft.issn=00912700&rft_id=info:doi/10.1177%2F0091270003256675 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Matrix metalloproteinase; Tetracyclines; Pharmacokinetics; Lipophilic; Carcinoma; Metastases; Plasma proteins; Body weight; Urine; Albumin; Kidney; Protein turnover; Dissolution; Excretion; Metabolism DO - http://dx.doi.org/10.1177/0091270003256675 ER - TY - JOUR T1 - On the Use of the Shapiro-Wilk Test in Two-Stage Adaptive Inference for Paired Data from Moderate to Very Heavy Tailed Distributions AN - 21091911; 11132345 AB - Paired data arises in a wide variety of applications where often the underlying distribution of the paired differences is unknown. When the differences are normally distributed, the t-test is optimum. On the other hand, if the differences are not normal, the t-test can have substantially less power than the appropriate optimum test, which depends on the unknown distribution. In textbooks, when the normality of the differences is questionable, typically the non-parametric Wilcoxon signed rank test is suggested. An adaptive procedure that uses the Shapiro-Wilk test of normality to decide whether to use the t-test or the Wilcoxon signed rank test has been employed in several studies. Faced with data from heavy tails, the U.S. Environmental Protection Agency (EPA) introduced another approach: it applies both the sign and t-tests to the paired differences, the alternative hypothesis is accepted if either test is significant. This paper investigates the statistical properties of a currently used adaptive test, the EPA's method and suggests an alternative technique. The new procedure is easy to use and generally has higher empirical power, especially when the differences are heavy-tailed, than currently used methods. JF - Biometrical Journal AU - Freidlin, B AU - Miao, W AU - Gastwirth, J L AD - Biometric Research Branch, National Cancer Institute, Bethesda, Maryland, 20892 USA, freidlinb@ctep.nci.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 887 EP - 900 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 45 IS - 7 SN - 0323-3847, 0323-3847 KW - Biotechnology and Bioengineering Abstracts KW - Statistics KW - Data processing KW - Tails KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21091911?accountid=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=Biometrical+Journal&rft.atitle=On+the+Use+of+the+Shapiro-Wilk+Test+in+Two-Stage+Adaptive+Inference+for+Paired+Data+from+Moderate+to+Very+Heavy+Tailed+Distributions&rft.au=Freidlin%2C+B%3BMiao%2C+W%3BGastwirth%2C+J+L&rft.aulast=Freidlin&rft.aufirst=B&rft.date=2003-10-01&rft.volume=45&rft.issue=7&rft.spage=887&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200390056 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Data processing; Tails; Statistics DO - http://dx.doi.org/10.1002/bimj.200390056 ER - TY - JOUR T1 - New Antibiotic Resistance Cassettes Suitable for Genetic Studies in Borrelia burgdorferi AN - 20951161; 6473530 AB - In this report we describe two distinct approaches to develop new antibiotic resistance cassettes that allow for efficient selection of Borrelia burgdorferi transformants. The first approach utilizes fusions of borrelial flagellar promoters to antibiotic resistance markers from other bacteria. The aacC1 gene, which encodes a gentamicin acetyltransferase, conferred a high level of gentamicin resistance in B. burgdorferi when expressed from these promoters. No cross-resistance occurred between this cassette and the kanamycin resistance cassette, which was previously developed in an analogous fashion. A second and different approach was taken to develop an efficient selectable marker that confers resistance to the antibiotic coumermycin A1. A synthetic gene was designed from the gyrB301 allele of the coumermycin-resistant B. burgdorferi strain B31-NGR by altering the coding sequence at the wobble position. The resulting gene, gyrB sub(syn), encodes a protein identical to the product of gyrB301, but the genes share only 66% nucleotide identity. The nucleotide sequence of gyrB sub(syn) is sufficiently divergent from the endogenous B. burgdorferigyrB gene to prevent recombination between them. The cassettes described in this paper improve our repertoire of genetic tools in B. burgdorferi. These studies also provide insight into parameters governing recombination and gene expression in B. burgdorferi. JF - Journal of Molecular Microbiology and Biotechnology AU - Elias, A F AU - Bono, J L AU - Kupko, JJ III AU - Stewart, P E AU - Krum, J G AU - Rosa, P A AD - Rocky Mountain Laboratories, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840 (USA), prosa@niaid.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 29 EP - 40 VL - 6 IS - 1 SN - 1464-1801, 1464-1801 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology; Biotechnology and Bioengineering Abstracts KW - Borrelia burgdorferi KW - Nucleotide sequence KW - Antibiotics KW - Kanamycin KW - Nucleotides KW - Gentamicin KW - Gene expression KW - Promoters KW - Recombination KW - Acetyltransferase KW - Cross-resistance KW - Antibiotic resistance KW - Flagella KW - W 30915:Pharmaceuticals & Vaccines KW - J 02795:Antibiotic resistance KW - G 07770:Bacteria KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20951161?accountid=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=New+Antibiotic+Resistance+Cassettes+Suitable+for+Genetic+Studies+in+Borrelia+burgdorferi&rft.au=Elias%2C+A+F%3BBono%2C+J+L%3BKupko%2C+JJ+III%3BStewart%2C+P+E%3BKrum%2C+J+G%3BRosa%2C+P+A&rft.aulast=Elias&rft.aufirst=A&rft.date=2003-10-01&rft.volume=6&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.issn=14641801&rft_id=info:doi/10.1159%2F000073406 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Gene expression; Gentamicin; Recombination; Promoters; Acetyltransferase; Nucleotide sequence; Kanamycin; Antibiotics; Cross-resistance; Nucleotides; Antibiotic resistance; Flagella; Borrelia burgdorferi DO - http://dx.doi.org/10.1159/000073406 ER - TY - JOUR T1 - An Alternative Perspective: A Critical Evaluation of the Waddell Threshold Extrapolation Model in Chemical Carcinogenesis AN - 19265820; 5843350 AB - In a recent Perspective article (Toxicologic Pathology 31: 260-262, 2003) Waddell asserts that he has developed a log linear extrapolation model that can demonstrate a threshold and resolve for once and for all the uncertainies associated with low dose cancer risk extrapolation. However, his method essentially forces, rather than demonstrates, a threshold, and has many serious flaws that result in significant under-estimation of low dose risk. It would be a serious mistake for the scientific community to adopt Waddell's log linear extrapolation model for chemical carcinogenesis risk assessment. JF - Toxicologic Pathology AU - Haseman, J K AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 468 EP - 470 VL - 31 IS - 5 SN - 0192-6233, 0192-6233 KW - evaluation KW - Toxicology Abstracts KW - Risk assessment KW - Carcinogenesis KW - Models KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19265820?accountid=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=Toxicologic+Pathology&rft.atitle=An+Alternative+Perspective%3A+A+Critical+Evaluation+of+the+Waddell+Threshold+Extrapolation+Model+in+Chemical+Carcinogenesis&rft.au=Haseman%2C+J+K&rft.aulast=Haseman&rft.aufirst=J&rft.date=2003-10-01&rft.volume=31&rft.issue=5&rft.spage=468&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Models; Risk assessment; Carcinogenesis ER - TY - JOUR T1 - Similar modes of polypeptide recognition by export chaperones in flagellar biosynthesis and type III secretion AN - 19243153; 5813394 AB - Assembly of the bacterial flagellum and type III secretion in pathogenic bacteria require cytosolic export chaperones that interact with mobile components to facilitate their secretion. Although their amino acid sequences are not conserved, the structures of several type III secretion chaperones revealed striking similarities between their folds and modes of substrate recognition. Here, we report the first crystallographic structure of a flagellar export chaperone, Aquifex aeolicus FliS. FliS adopts a novel fold that is clearly distinct from those of the type III secretion chaperones, indicating that they do not share a common evolutionary origin. However, the structure of FliS in complex with a fragment of FliC (flagellin) reveals that, like the type III secretion chaperones, flagellar export chaperones bind their target proteins in extended conformation and suggests that this mode of recognition may be widely used in bacteria. JF - Nature Structural Biology AU - Evdokimov, A G AU - Phan, J AU - Tropea, JE AU - Routzahn, K M AU - Peters, HK III AU - Pokross, M AU - Waugh, D S AD - Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, PO Box B, Frederick, MD 21702-1201, USA, waughd@ncifcrf.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 789 EP - 793 VL - 10 IS - 10 SN - 1072-8368, 1072-8368 KW - secretion system (type III) KW - Microbiology Abstracts B: Bacteriology KW - Aquifex aeolicus KW - Crystallography KW - Chaperones KW - Flagella KW - Conformation KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19243153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Structural+Biology&rft.atitle=Similar+modes+of+polypeptide+recognition+by+export+chaperones+in+flagellar+biosynthesis+and+type+III+secretion&rft.au=Evdokimov%2C+A+G%3BPhan%2C+J%3BTropea%2C+JE%3BRoutzahn%2C+K+M%3BPeters%2C+HK+III%3BPokross%2C+M%3BWaugh%2C+D+S&rft.aulast=Evdokimov&rft.aufirst=A&rft.date=2003-10-01&rft.volume=10&rft.issue=10&rft.spage=789&rft.isbn=&rft.btitle=&rft.title=Nature+Structural+Biology&rft.issn=10728368&rft_id=info:doi/10.1038%2Fnsb982 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Crystallography; Chaperones; Conformation; Flagella; Aquifex aeolicus DO - http://dx.doi.org/10.1038/nsb982 ER - TY - JOUR T1 - Specificity grafting of human antibody frameworks selected from a phage display library: generation of a highly stable humanized anti-CD22 single-chain Fv fragment AN - 19229943; 5816192 AB - A prerequisite for the enrichment of antibodies screened from phage display libraries is their stable expression on a phage during multiple selection rounds. Thus, if stringent panning procedures are employed, selection is simultaneously driven by antigen affinity, stability and solubility. To take advantage of robust pre-selected scaffolds of such molecules, we grafted single-chain Fv (scFv) antibodies, previously isolated from a human phage display library after multiple rounds of in vitro panning on tumor cells, with the specificity of the clinically established murine monoclonal anti-CD22 antibody RFB4. We show that a panel of grafted scFvs retained the specificity of the murine monoclonal antibody, bound to the target antigen with high affinity (6.4-9.6 nM), and exhibited exceptional biophysical stability with retention of 89-93% of the initial binding activity after 6 days of incubation in human serum at 37 degree C. Selection of stable human scaffolds with high sequence identity to both the human germline and the rodent frameworks required only a small number of murine residues to be retained within the human frameworks in order to maintain the structural integrity of the antigen binding site. We expect this approach may be applicable for the rapid generation of highly stable humanized antibodies with low immunogenic potential. JF - Protein Engineering AU - Krauss, J AU - Arndt, MAE AU - Martin, ACR AU - Liu, H AU - Rybak, S M AD - National Cancer Institute at Frederick, Frederick, MD 21702, USA, rybak@ncifcrf.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 753 EP - 759 VL - 16 IS - 10 SN - 0269-2139, 0269-2139 KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - CD22 antigen KW - Antibodies KW - Protein engineering KW - Gene libraries KW - Phage display KW - Fv KW - W3 33375:Antibodies KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19229943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+Engineering&rft.atitle=Specificity+grafting+of+human+antibody+frameworks+selected+from+a+phage+display+library%3A+generation+of+a+highly+stable+humanized+anti-CD22+single-chain+Fv+fragment&rft.au=Krauss%2C+J%3BArndt%2C+MAE%3BMartin%2C+ACR%3BLiu%2C+H%3BRybak%2C+S+M&rft.aulast=Krauss&rft.aufirst=J&rft.date=2003-10-01&rft.volume=16&rft.issue=10&rft.spage=753&rft.isbn=&rft.btitle=&rft.title=Protein+Engineering&rft.issn=02692139&rft_id=info:doi/10.1093%2Fprotein%2Fgzg096 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antibodies; Phage display; Gene libraries; Fv; CD22 antigen; Protein engineering DO - http://dx.doi.org/10.1093/protein/gzg096 ER - TY - JOUR T1 - An Approach to Assessment of Endocrine Disruption in the National Children's Study AN - 19229599; 5801269 AB - In this article we consider the importance of assessing endocrine disruption in a large new cohort that has been proposed, the National Children's Study (NCS). We briefly review evidence that endocrine disruption is a potentially important hypothesis for human studies and weigh the need to assess endocrine disruption in the NCS. We note the salient features of earlier, similar cohort studies that serve as reference points for the design of the NCS. Finally, we discuss features of the NCS that would allow or enhance assessment of endocrine disruption, even if endocrine disruption were not a primary hypothesis motivating the study. At this time, the evidence supporting endocrine disruption in humans with background-level exposures is not strong. Thus, a compelling rationale for the NCS will probably need to be based on core hypotheses that focus on other issues. Nonetheless, if properly designed, the NCS could serve as an excellent resource for investigating future hypotheses regarding endocrine disruption. JF - Environmental Health Perspectives AU - Longnecker, M P AU - Bellinger, D C AU - Crews, D AU - Eskenazi, B AU - Silbergeld, E K AU - Woodruff, T J AU - Susser, E S AD - NIEHS, Epidemiology Branch, P.O. Box 12233, Research Triangle Park, NC 27709 USA, longnecker@niehs.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 1691 EP - 1697 VL - 111 IS - 13 SN - 0091-6765, 0091-6765 KW - endocrine disruptors KW - man KW - Toxicology Abstracts KW - Risk assessment KW - Reviews KW - Children KW - Public health KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19229599?accountid=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=An+Approach+to+Assessment+of+Endocrine+Disruption+in+the+National+Children%27s+Study&rft.au=Longnecker%2C+M+P%3BBellinger%2C+D+C%3BCrews%2C+D%3BEskenazi%2C+B%3BSilbergeld%2C+E+K%3BWoodruff%2C+T+J%3BSusser%2C+E+S&rft.aulast=Longnecker&rft.aufirst=M&rft.date=2003-10-01&rft.volume=111&rft.issue=13&rft.spage=1691&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Fehp.5800 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Risk assessment; Reviews; Children; Public health DO - http://dx.doi.org/10.1289/ehp.5800 ER - TY - JOUR T1 - Role of the extracellular matrix in morphogenesis AN - 19158983; 5746148 AB - The extracellular matrix is a complex, dynamic and critical component of all tissues. It functions as a scaffold for tissue morphogenesis, provides cues for cell proliferation and differentiation, promotes the maintenance of differentiated tissues and enhances the repair response after injury. Various amounts and types of collagens, adhesion molecules, proteoglycans, growth factors and cytokines or chemokines are present in the tissue- and temporal- specific extracellular matrices. Tissue morphogenesis is mediated by multiple extracellular matrix components and by multiple active sites on some of these components. Biologically active extracellular matrix components may have use in tissue repair, regeneration and engineering, and in programming stem cells for tissue replacement. JF - Current Opinion in Biotechnology AU - Kleinman, H K AU - Philp, D AU - Hoffman, M P AD - Cell Biology Section, CDBRB, National Institute of Dental and Craniofacial Research, NIH, 30 Convent Drive, MSC 4370, Bethesda, MD 20892, USA, hkleinman@dir.nidcr.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 526 EP - 532 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 14 IS - 5 SN - 0958-1669, 0958-1669 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Tissues KW - Chemokines KW - Morphogenesis KW - Collagen KW - Stem cells KW - Extracellular matrix KW - Reviews KW - Cytokines KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19158983?accountid=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+Biotechnology&rft.atitle=Role+of+the+extracellular+matrix+in+morphogenesis&rft.au=Kleinman%2C+H+K%3BPhilp%2C+D%3BHoffman%2C+M+P&rft.aulast=Kleinman&rft.aufirst=H&rft.date=2003-10-01&rft.volume=14&rft.issue=5&rft.spage=526&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Biotechnology&rft.issn=09581669&rft_id=info:doi/10.1016%2Fj.copbio.2003.08.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Extracellular matrix; Morphogenesis; Cytokines; Chemokines; Collagen; Tissues; Stem cells DO - http://dx.doi.org/10.1016/j.copbio.2003.08.002 ER - TY - JOUR T1 - Multiple methionine sulfoxide reductase genes in Staphylococcus aureus: expression of activity and roles in tolerance of oxidative stress AN - 19143981; 5765245 AB - Staphylococcus aureus contains three genes encoding MsrA-specific methionine sulfoxide reductase (Msr) activity (msrA1, msrA2 and msrA3) and an additional gene that encodes MsrB-specific Msr activity. Data presented here suggest that MsrA1 is the major contributor of the MsrA activity in S. aureus. In mutational analysis, while the total Msr activity in msrA2 mutant was comparable to that of the parent, Msr activity was significantly up-regulated in the msrA1 or msrA1 msrA2 double mutant. Assessment of substrate specificity together with increased reactivity of the cell-free protein extracts of the msrA1 mutants to anti-MsrB polyclonal antibodies in Western analysis provided evidence that increased Msr activity was due to elevated synthesis of MsrB in the MsrA1 mutants. Previously, it was reported that oxacillin treatment of S. aureus cells led to induced synthesis of MsrA1 and a mutation in msrA1 increased the susceptibility of the organism to H sub(2)O sub(2). A mutation in the msrA2 gene, however, was not significant for the bacterial oxidative stress response. In complementation assays, while the msrA2 gene was unable to complement the msrA1 msrA2 double mutant for H sub(2)O sub(2) resistance, the same gene restored H sub(2)O sub(2) tolerance in the double mutant when placed under the control of the msrA1 promoter. However, msrA1 which was able to complement the oxidative stress response in msrA1 mutants could not restore the tolerance of the msrA1 msrA2 mutants to H sub(2)O sub(2) when placed under the control of the msrA2 promoter. Additionally, although the oxacillin minimum inhibitory concentration of the msrA1 mutant was comparable to that of the wild-type parent, in shaking liquid culture, the msrA1 mutant responded more efficiently to sublethal doses of oxacillin. The data suggest complex regulation of Msr proteins and a more significant physiological role for msrA1/msrB in S. aureus. JF - Microbiology AU - Singh, V K AU - Moskovitz, J AD - Laboratory of Biochemistry, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA, MoskoviJ@NHLBI.NIH.GOV Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 2739 EP - 2747 VL - 149 IS - 10 SN - 1350-0872, 1350-0872 KW - methionine sulfoxide reductase KW - msrA gene KW - Microbiology Abstracts B: Bacteriology KW - Oxidative stress KW - Oxacillin KW - Staphylococcus aureus KW - Mutants KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19143981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbiology&rft.atitle=Multiple+methionine+sulfoxide+reductase+genes+in+Staphylococcus+aureus%3A+expression+of+activity+and+roles+in+tolerance+of+oxidative+stress&rft.au=Singh%2C+V+K%3BMoskovitz%2C+J&rft.aulast=Singh&rft.aufirst=V&rft.date=2003-10-01&rft.volume=149&rft.issue=10&rft.spage=2739&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&rft_id=info:doi/10.1099%2Fmic.0.26442-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Staphylococcus aureus; Mutants; Oxacillin; Oxidative stress DO - http://dx.doi.org/10.1099/mic.0.26442-0 ER - TY - JOUR T1 - Identification of PDGFR as a receptor for AAV-5 transduction AN - 18955586; 5741816 AB - Understanding the process of vector transduction has important implications for the application and optimal use of a vector system for human gene therapy. Recent studies with vectors based on adeno-associated virus type 5 (AAV-5) have shown utility of this vector system in the lung, central nervous system, muscle and eye. To understand the natural tropism of this virus and to identify proteins necessary for AAV-5 transduction, we characterized 43 cell lines as permissive or nonpermissive for AAV-5 transduction and compared the gene expression profiles derived from cDNA microarray analyses of those cell lines. A statistically significant correlation was observed between expression of the platelet-derived growth factor receptor (PDGFR- alpha -polypeptide) and AAV-5 transduction. Subsequent experiments confirmed the role of PDGFR- alpha and PDGFR- beta as receptors for AAV-5. The tropism of AAV-5 in vivo also correlated with the expression pattern of PDGFR- alpha . JF - Nature Medicine AU - Di Pasquale, G AU - Davidson, B L AU - Stein, C S AU - Martins, I AU - Scudiero, D AU - Monks, A AU - Chiorini, JA AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA, Jchiorini@dir.nidcr.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 1306 EP - 1312 VL - 9 IS - 10 SN - 1078-8956, 1078-8956 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Adeno-associated virus 5 KW - Gene therapy KW - Platelet-derived growth factor receptors KW - Transduction KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18955586?accountid=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=Identification+of+PDGFR+as+a+receptor+for+AAV-5+transduction&rft.au=Di+Pasquale%2C+G%3BDavidson%2C+B+L%3BStein%2C+C+S%3BMartins%2C+I%3BScudiero%2C+D%3BMonks%2C+A%3BChiorini%2C+JA&rft.aulast=Di+Pasquale&rft.aufirst=G&rft.date=2003-10-01&rft.volume=9&rft.issue=10&rft.spage=1306&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/10.1038%2Fnm929 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adeno-associated virus 5; Transduction; Platelet-derived growth factor receptors; Gene therapy; Expression vectors DO - http://dx.doi.org/10.1038/nm929 ER - TY - JOUR T1 - Exposing the roots of hair cell regeneration in the ear AN - 18952610; 5741664 AB - As many as 25 million Americans experience some form of progressive hearing loss, and that number will increase as the population continues to live longer. By far, the primary cause of age-related hearing loss is the loss of mechanosensory hair cells located within a specialized sensory epithelium that extends along the coiled cochlea of the inner ear. Although hair cells are not neurons, the two cell types have many similar characteristics, including electrical depolarization in response to an excitatory stimulus and, at least in mammals, an only limited ability to regenerate new cells after the embryonic period. In contrast, hair-cell regeneration and recovery of hearing occurs in most nonmammalian vertebrates, primarily through the proliferation of stem or progenitor cells that reside within the hair-cell sensory epithelia. Based on these observations, some researchers have suggested that a similar population of stem or progenitor cells might reside in the mammalian ear. In this issue, Li et al. suceed in isolating a type of stem-like cell from the hair-cell sensory epithelia of adult mice. These cells meet all the major criteria for stem cells, including the ability to form spheres (clusters) of floating cells through mitosis and to generate pluripotent progenitor cells that can develop into cell types derived from different germ layers. These stem cells can also give rise to mechanosensory hair cells, both in vitro and when transplanted into the developing ears of embryonic chicks. JF - Nature Medicine AU - Kelley, M W AD - Section on Developmental Neuroscience, National Institute on Deafness and other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, Maryland 20850, USA, kelleymt@nidcd.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 1257 EP - 1259 VL - 9 IS - 10 SN - 1078-8956, 1078-8956 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Hair cells KW - Reviews KW - Regeneration KW - Roots KW - Embryos KW - Ear KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18952610?accountid=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=Exposing+the+roots+of+hair+cell+regeneration+in+the+ear&rft.au=Kelley%2C+M+W&rft.aulast=Kelley&rft.aufirst=M&rft.date=2003-10-01&rft.volume=9&rft.issue=10&rft.spage=1257&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 - Regeneration; Hair cells; Ear; Roots; Reviews; Embryos ER - TY - JOUR T1 - An application system for automation of constant-time radio frequency electron paramagnetic resonance imaging AN - 18951784; 5695996 AB - A Windows based application system for data collection, Fourier reconstruction and analysis of pure phase encoded constant-time radio frequency electron paramagnetic resonance (EPR) images, is described. The graphical user interface (GUI) of the system was written in MATLAB version 5.0, using its built-in GUI utilities. Design considerations of the application system included speed, flexibility and user-friendly data display and analysis. To maximize the speed of image data collection, MATLAB's built-in C interface system, MEX was not used for data collection. Instead, MATLAB programs call the C programs from the dos prompt directly, based on the data collection parameters entered through the GUI. Computational procedures included various digital signal-processing steps such as filtering, interpolation etc. for the Fourier reconstruction of 2D, and 3D EPR images from the pure phase encoded data. Examples of 2D images illustrating the performance of the system are presented. Although the application system has been developed for the specific purpose of EPR imaging, it can easily be adapted to other areas such as magnetic resonance microscopy as well. JF - Computer Methods and Programs in Biomedicine AU - Taube, A G AU - Subramanian, S AU - Murugesan, R AU - Devasahayam, N AU - Mitchell, J B AU - Krishna, M C AU - Cook, JA AD - Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, murali@helix.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 127 EP - 138 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo@elsevier.com], [URL:http://www.elsevier.nl] VL - 72 IS - 2 SN - 0169-2607, 0169-2607 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - E.S.R. KW - Computer programs KW - Magnetic resonance imaging KW - Automation KW - Computer applications KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18951784?accountid=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=Computer+Methods+and+Programs+in+Biomedicine&rft.atitle=An+application+system+for+automation+of+constant-time+radio+frequency+electron+paramagnetic+resonance+imaging&rft.au=Taube%2C+A+G%3BSubramanian%2C+S%3BMurugesan%2C+R%3BDevasahayam%2C+N%3BMitchell%2C+J+B%3BKrishna%2C+M+C%3BCook%2C+JA&rft.aulast=Taube&rft.aufirst=A&rft.date=2003-10-01&rft.volume=72&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Computer+Methods+and+Programs+in+Biomedicine&rft.issn=01692607&rft_id=info:doi/10.1016%2FS0169-2607%2802%2900124-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Computer applications; Computer programs; Magnetic resonance imaging; Automation; E.S.R. DO - http://dx.doi.org/10.1016/S0169-2607(02)00124-4 ER - TY - JOUR T1 - Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coli AN - 18886360; 5741610 AB - RyhB is a small antisense regulatory RNA that is repressed by the Fur repressor and negatively regulates at least six mRNAs encoding Fe-binding or Fe-storage proteins in Escherichia coli. When Fe is limiting, RyhB levels rise, and target mRNAs are rapidly degraded. RyhB is very stable when measured after treatment of cells with the transcription inhibitor rifampicin, but is unstable when overall mRNA transcription continues. We propose that RyhB turnover is coupled to and dependent on pairing with the target mRNAs. Degradation of both mRNA targets and RyhB is dependent on RNase E and is slowed in degradosome mutants. RyhB requires the RNA chaperone Hfq. In the absence of Hfq, RyhB is unstable, even when general transcription is inhibited; degradation is dependent upon RNase E. Hfq and RNase E bind similar sites on the RNA; pairing may allow loss of Hfq and access by RNase E. Two other Hfq-dependent small RNAs, DsrA and OxyS, are also stable when overall transcription is off, and unstable when it is not, suggesting that they, too, are degraded when their target mRNAs are available for pairing. Thus, this large class of regulatory RNAs share an unexpected intrinsic mechanism for shutting off their action. JF - Genes & Development AU - Masse, E AU - Escorcia, F E AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA, susang@helix.nih.gov Y1 - 2003/10/01/ PY - 2003 DA - 2003 Oct 01 SP - 2374 EP - 2383 VL - 17 IS - 19 SN - 0890-9369, 0890-9369 KW - Hfq protein KW - RhyB gene KW - Ribonuclease E KW - sRNA KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02726:RNA and ribosomes KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18886360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+Development&rft.atitle=Coupled+degradation+of+a+small+regulatory+RNA+and+its+mRNA+targets+in+Escherichia+coli&rft.au=Masse%2C+E%3BEscorcia%2C+F+E%3BGottesman%2C+S&rft.aulast=Masse&rft.aufirst=E&rft.date=2003-10-01&rft.volume=17&rft.issue=19&rft.spage=2374&rft.isbn=&rft.btitle=&rft.title=Genes+%26+Development&rft.issn=08909369&rft_id=info:doi/10.1101%2Fgad.1127103 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1101/gad.1127103 ER - TY - JOUR T1 - Evolutionary connections between bacterial and eukaryotic signaling systems: a genomic perspective AN - 18884355; 5744059 AB - Recent advances in microbial genomics suggest that several protein domains are common to bacterial and eukaryotic regulatory proteins. In particular, developmentally and morphologically complex prokaryotes appear to share several signaling modules with eukaryotes. New experimental studies and information from domain architectures point to several similar mechanistic themes in bacterial and eukaryotic signaling proteins. Laterally transferred protein domains, originally of bacterial provenance, appear to have contributed to the evolution of sensory pathways related to light, redox and nitric oxide signaling, and developmental pathways, such as Notch, cytokine and cytokinin signaling in eukaryotes. JF - Current Opinion in Microbiology AU - Aravind, L AU - Anantharaman, V AU - Iyer, L M AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, aravind@ncbi.nlm.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 490 EP - 497 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 6 IS - 5 SN - 1369-5274, 1369-5274 KW - Notch protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02726:RNA and ribosomes KW - N 14100:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18884355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Microbiology&rft.atitle=Evolutionary+connections+between+bacterial+and+eukaryotic+signaling+systems%3A+a+genomic+perspective&rft.au=Aravind%2C+L%3BAnantharaman%2C+V%3BIyer%2C+L+M&rft.aulast=Aravind&rft.aufirst=L&rft.date=2003-10-01&rft.volume=6&rft.issue=5&rft.spage=490&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Microbiology&rft.issn=13695274&rft_id=info:doi/10.1016%2Fj.mib.2003.09.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.mib.2003.09.003 ER - TY - JOUR T1 - Minimizing immunogenicity of the SDR-grafted humanized antibody CC49 by genetic manipulation of the framework residues AN - 18883105; 5738919 AB - The murine mAb CC49 specifically recognizes a tumor-associated glycoprotein (TAG)-72, which is expressed on the majority of human carcinomas. This Ab has potential applications in the diagnosis and treatment of human carcinomas. However, patients receiving murine CC49 generate human anti-murine Ab (HAMA) responses, preventing repeated administration of the Ab for effective treatment. To minimize the HAMA response, two versions of humanized CC49 (HuCC49) were developed: (a) HuCC49 and (b) HuCC49V10 (V10). HuCC49 was developed by grafting the CC49 CDRs, while V10 was generated by grafting only the specificity determining residues (SDRs) of the CC49 onto the frameworks of the human Abs. During the generation of both HuCC49 and V10, a few murine framework residues that were believed to be essential for the integrity of the Ag-binding site were retained. However, the indispensability of these residues for the Ag-binding activity of CC49 has not been experimentally validated. In this study, an array of V10 variants were generated by replacing, by site-specific mutagenesis, the murine framework residues that were retained in the humanized Ab with their counterparts in the human templates. The variants were tested for their (a) Ag-binding activity and (b) reactivity to sera from patients who were previously administered murine CC49 in a clinical trial. One such variant, V59, compared to the parental V10, shows a significant decrease in its reactivity to the anti-variable region Abs present in the patients' sera, while it binds to the TAG-72 Ag with a slightly higher affinity. Variant 59, which is expected to be minimally immunogenic because of its low sera reactivity, is a potentially useful clinical reagent against human carcinomas. In this study, we show for the first time that experimental validation rather than reliance on the protein data bank (PDB) should be the criterion for the indispensability of framework residues for the humanization of any murine Ab to retain its Ag-binding property and reduce its immunogenicity in patients. JF - Molecular Immunology AU - Gonzales, N R AU - Padlan, E A AU - De Pascalis, R AU - Schuck, P AU - Schlom, J AU - Kashmiri, SVS AD - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, Room 8B09, 10 Center Drive, Building 10, Bethesda, MD 20892-1750, USA, js141c@nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 337 EP - 349 PB - Elsevier Science Ltd., Pergamon, P.O. Box 800 Kidlington Oxford OX5 1DX UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 40 IS - 6 SN - 0161-5890, 0161-5890 KW - TAG-72 protein KW - glycoprotein gp72 KW - mice KW - tumor-associated glycoprotein 72 KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33375:Antibodies KW - G 07240:Immunogenetics 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/18883105?accountid=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+Immunology&rft.atitle=Minimizing+immunogenicity+of+the+SDR-grafted+humanized+antibody+CC49+by+genetic+manipulation+of+the+framework+residues&rft.au=Gonzales%2C+N+R%3BPadlan%2C+E+A%3BDe+Pascalis%2C+R%3BSchuck%2C+P%3BSchlom%2C+J%3BKashmiri%2C+SVS&rft.aulast=Gonzales&rft.aufirst=N&rft.date=2003-10-01&rft.volume=40&rft.issue=6&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Molecular+Immunology&rft.issn=01615890&rft_id=info:doi/10.1016%2FS0161-5890%2803%2900166-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0161-5890(03)00166-4 ER - TY - JOUR T1 - High Disease Burden of Diarrhea Due to Enterotoxigenic Escherichia coli among Rural Egyptian Infants and Young Children AN - 18877131; 5732084 AB - The incidence of enterotoxigenic Escherichia coli diarrhea among Egyptian children was 1.5 episodes per child per year and accounted for 66% of all first episodes of diarrhea after birth. The incidence increased from 1.7 episodes per child per year in the first 6 months of life to 2.3 in the second 6 months and declined thereafter. JF - Journal of Clinical Microbiology AU - Rao, M R AU - Abu-Elyazeed, R AU - Savarino, S J AU - Naficy, AB AU - Wierzba, T F AU - Abdel-Messih, I AU - Shaheen, H AU - Frenck, RW Jr AU - Svennerholm, A-M AU - Clemens, J D AD - PIPB, NIAID, NIH, 6610 Rockledge Dr., Room 5044, Bethesda, MD 20892, mr8u@nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 4862 EP - 4864 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 41 IS - 10 SN - 0095-1137, 0095-1137 KW - Microbiology Abstracts B: Bacteriology KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18877131?accountid=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=High+Disease+Burden+of+Diarrhea+Due+to+Enterotoxigenic+Escherichia+coli+among+Rural+Egyptian+Infants+and+Young+Children&rft.au=Rao%2C+M+R%3BAbu-Elyazeed%2C+R%3BSavarino%2C+S+J%3BNaficy%2C+AB%3BWierzba%2C+T+F%3BAbdel-Messih%2C+I%3BShaheen%2C+H%3BFrenck%2C+RW+Jr%3BSvennerholm%2C+A-M%3BClemens%2C+J+D&rft.aulast=Rao&rft.aufirst=M&rft.date=2003-10-01&rft.volume=41&rft.issue=10&rft.spage=4862&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/10.1128%2FJCM.41.10.4862-4864.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JCM.41.10.4862-4864.2003 ER - TY - JOUR T1 - Serial Granulocyte Transfusions as a Treatment for Sepsis Due to Multidrug- Resistant Pseudomonas aeruginosa in a Neutropenic Patient AN - 18875803; 5732065 AB - The emergence of multidrug-resistant Pseudomonas aeruginosa (MRPA) has become a major clinical problem. We successfully treated MRPA sepsis in a neutropenic patient undergoing peripheral blood stem cell transplantation with serial granulocyte transfusions. Granulocyte transfusion should be considered as a treatment for severe infection in patients with neutropenia. JF - Journal of Clinical Microbiology AU - Lin, Y-W AU - Adachi, S AU - Watanabe, K-I AU - Umeda, K AU - Nakahata, T AD - ATC/GB/CCR/NCI/NIH, 301 N. Stonestreet Ave., Rockville, MD 20892-4605, linying@mail.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 4892 EP - 4893 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 41 IS - 10 SN - 0095-1137, 0095-1137 KW - Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18875803?accountid=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=Serial+Granulocyte+Transfusions+as+a+Treatment+for+Sepsis+Due+to+Multidrug-+Resistant+Pseudomonas+aeruginosa+in+a+Neutropenic+Patient&rft.au=Lin%2C+Y-W%3BAdachi%2C+S%3BWatanabe%2C+K-I%3BUmeda%2C+K%3BNakahata%2C+T&rft.aulast=Lin&rft.aufirst=Y-W&rft.date=2003-10-01&rft.volume=41&rft.issue=10&rft.spage=4892&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/10.1128%2FJCM.41.10.4892-4893.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JCM.41.10.4892-4893.2003 ER - TY - JOUR T1 - Novel bis-Tetrahydrofuranylurethane-Containing Nonpeptidic Protease Inhibitor (PI) UIC-94017 (TMC114) with Potent Activity against Multi-PI- Resistant Human Immunodeficiency Virus In Vitro AN - 18874945; 5720895 AB - We designed, synthesized, and identified UIC-94017 (TMC114), a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing a 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF) and a sulfonamide isostere which is extremely potent against laboratory HIV-1 strains and primary clinical isolates (50% inhibitory concentration (IC sub(50)), similar to 0.003 mu M; IC sub(90), similar to 0.009 mu M) with minimal cytotoxicity (50% cytotoxic concentration for CD4 super(+) MT-2 cells, 74 mu M). UIC- 94017 blocked the infectivity and replication of each of HIV-1 sub(NL4-3) variants exposed to and selected for resistance to saquinavir, indinavir, nelfinavir, or ritonavir at concentrations up to 5 mu M (IC sub(50)s, 0.003 to 0.029 mu M), although it was less active against HIV-1 sub(NL4-3) variants selected for resistance to amprenavir (IC sub(50), 0.22 mu M). UIC-94017 was also potent against multi-PI-resistant clinical HIV-1 variants isolated from patients who had no response to existing antiviral regimens after having received a variety of antiviral agents. Structural analyses revealed that the close contact of UIC- 94017 with the main chains of the protease active-site amino acids (Asp-29 and Asp-30) is important for its potency and wide spectrum of activity against multi-PI-resistant HIV-1 variants. Considering the favorable pharmacokinetics of UIC-94017 when administered with ritonavir, the present data warrant that UIC- 94017 be further developed as a potential therapeutic agent for the treatment of primary and multi-PI-resistant HIV-1 infections. JF - Antimicrobial Agents & Chemotherapy AU - Koh, Y AU - Nakata, H AU - Maeda, K AU - Ogata, H AU - Bilcer, G AU - Devasamudram, T AU - Kincaid, J F AU - Boross, P AU - Wang, Y-F AU - Tie, Y AU - Volarath, P AU - Gaddis, L AU - Harrison, R W AU - Weber, I T AU - Ghosh, A K AU - Mitsuya, H AD - Department of Internal Medicine II, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-8556, Japan, hm21q@nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 3123 EP - 3129 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 47 IS - 10 SN - 0066-4804, 0066-4804 KW - HIV-1 KW - TMC114 KW - UIC-94017 KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Bioengineering Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - V 22002:AIDS: Molecular and in vitro aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18874945?accountid=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=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Novel+bis-Tetrahydrofuranylurethane-Containing+Nonpeptidic+Protease+Inhibitor+%28PI%29+UIC-94017+%28TMC114%29+with+Potent+Activity+against+Multi-PI-+Resistant+Human+Immunodeficiency+Virus+In+Vitro&rft.au=Koh%2C+Y%3BNakata%2C+H%3BMaeda%2C+K%3BOgata%2C+H%3BBilcer%2C+G%3BDevasamudram%2C+T%3BKincaid%2C+J+F%3BBoross%2C+P%3BWang%2C+Y-F%3BTie%2C+Y%3BVolarath%2C+P%3BGaddis%2C+L%3BHarrison%2C+R+W%3BWeber%2C+I+T%3BGhosh%2C+A+K%3BMitsuya%2C+H&rft.aulast=Koh&rft.aufirst=Y&rft.date=2003-10-01&rft.volume=47&rft.issue=10&rft.spage=3123&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/10.1128%2FAAC.47.10.3123-3129.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/AAC.47.10.3123-3129.2003 ER - TY - JOUR T1 - Generation and characterization of a cold-adapted influenza A H9N2 reassortant as a live pandemic influenza virus vaccine candidate AN - 18873831; 5718388 AB - H9N2 subtype influenza A viruses have been identified in avian species worldwide and were isolated from humans in 1999, raising concerns about their pandemic potential and prompting the development of candidate vaccines to protect humans against this subtype of influenza A virus. Reassortant H1N1 and H3N2 human influenza A viruses with the internal genes of the influenza A/Ann Arbor/6/60 (H2N2) (AA) cold-adapted (ca) virus have proven to be attenuated and safe as live virus vaccines in humans. Using classical genetic reassortment, we generated a reassortant virus (G9/AA ca) that contains the hemagglutinin and neuraminidase genes from influenza A/chicken/Hong Kong/G9/97 (H9N2) (G9) and six internal gene segments from the AA ca virus. When administered intranasally, the reassortant virus was immunogenic and protected mice from subsequent challenge with wild-type H9N2 viruses, although it was restricted in replication in the respiratory tract of mice. The G9/AA ca virus bears properties that are desirable in a vaccine for humans and is available for clinical evaluation and use, should the need arise. JF - Vaccine AU - Chen, H AU - Matsuoka, Y AU - Swayne, D AU - Chen, Q AU - Cox, N J AU - Murphy, B R AU - Subbarao, K AD - Influenza Branch, CDC, Atlanta, GA, USA, ksubbarao@niaid.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 4430 EP - 4436 PB - Butterworth-Heinemann, 313 Washington St. Newton MA 02158 USA VL - 21 IS - 27-28 SN - 0264-410X, 0264-410X KW - mice KW - Virology & AIDS Abstracts; Immunology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - A 01097:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18873831?accountid=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=Vaccine&rft.atitle=Generation+and+characterization+of+a+cold-adapted+influenza+A+H9N2+reassortant+as+a+live+pandemic+influenza+virus+vaccine+candidate&rft.au=Chen%2C+H%3BMatsuoka%2C+Y%3BSwayne%2C+D%3BChen%2C+Q%3BCox%2C+N+J%3BMurphy%2C+B+R%3BSubbarao%2C+K&rft.aulast=Chen&rft.aufirst=H&rft.date=2003-10-01&rft.volume=21&rft.issue=27-28&rft.spage=4430&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2FS0264-410X%2803%2900430-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0264-410X(03)00430-4 ER - TY - JOUR T1 - Identification of Peptides That Mimic the Pertussis Toxin Binding Site on Bovine Fetuin AN - 18873550; 5728870 AB - The introduction of acellular pertussis vaccines has greatly enhanced the safety profile of vaccines to prevent whooping cough. Pertussis toxin (Ptx) is one component produced by Bordetella pertussis that is contained in all of these vaccines, either in combination with other known pertussis virulence factors or as the sole pertussis component, combined with tetanus and diphtheria toxoids. A hydrogen peroxide toxoid of Ptx has been shown to be efficacious in preventing pertussis infections in a mass vaccination trial and is presently licensed in the United States and Europe. The industrial production of Ptx can be performed through the cultivation of B. pertussis in well-defined growth media, in which the components can be well characterized and their origins can be documented. Once the bacteria are removed from the culture, Ptx can be isolated from the supernatant and purified by using the technique described by Sekura. The only drawback of this procedure, which combines two affinity chromatography steps, one with Blue Sepharose and a second with matrix-bound bovine fetuin (BF), is the source and purity of the BF. Concern about vaccine preparations that may possibly risk contamination by material associated with bovine spongioform encephalopathy has continued to increase. We thus sought a replacement for the BF affinity chromatography and, more specifically, for the glycosidic moiety on BF. We describe here the identification of a seven-amino-acid peptide that mimics the glycosidic moiety on BF to which Ptx binds. Furthermore, we have constructed an affinity column containing this peptide that can be used to replace BF in Ptx purification. Finally, we used the X-ray crystallographic structure of Ptx bound to the oligosaccharide moiety of BF as a scaffold and replaced the oligosaccharide with the peptide. JF - Applied and Environmental Microbiology AU - Bogdan, JA AU - Yuan, W AU - Long-Rowe, KO AU - Sarwar, J AU - Brucker, E A AU - Blake AD - National Institute of Allergy and Infectious Diseases, 6700-B Rockledge Dr., MSC 7616, Bethesda, MD 20892-7616, jbogdan@niaid.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 6272 EP - 6279 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 69 IS - 10 SN - 0099-2240, 0099-2240 KW - cattle KW - fetuin KW - oligosaccharides KW - Microbiology Abstracts B: Bacteriology KW - J 02822:Biosynthesis and physicochemical properties UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18873550?accountid=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=Identification+of+Peptides+That+Mimic+the+Pertussis+Toxin+Binding+Site+on+Bovine+Fetuin&rft.au=Bogdan%2C+JA%3BYuan%2C+W%3BLong-Rowe%2C+KO%3BSarwar%2C+J%3BBrucker%2C+E+A%3BBlake&rft.aulast=Bogdan&rft.aufirst=JA&rft.date=2003-10-01&rft.volume=69&rft.issue=10&rft.spage=6272&rft.isbn=&rft.btitle=&rft.title=Applied+and+Environmental+Microbiology&rft.issn=00992240&rft_id=info:doi/10.1128%2FAEM.69.10.6272-6279.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/AEM.69.10.6272-6279.2003 ER - TY - JOUR T1 - Purified complexes of HIV-1 envelope glycoproteins with CD4 and CCR5(CXCR4): Production, characterization and immunogenicity AN - 18873512; 5718364 AB - The ability to readily elicit broadly neutralizing antibodies to HIV-1 remains elusive. We and others have hypothesized that interaction of the viral envelope glycoprotein (Env, gp120-gp41) with its receptor molecules could enhance the exposure of conserved epitopes that may facilitate the elicitation of broadly neutralizing antibodies. The Env-CD4-coreceptor complexes mediate HIV-1 entry into cells and serve as a major target for inhibitors of this process. To begin to evaluate their potential also as vaccine immunogens we produced relatively large amounts of complexes of purified recombinant soluble truncated Env, gp140 sub(89.6) or gp120 sub(89.6), with CD4 and CCR5 or CXCR4. We found that gp140(gp120)-CD4-CCR5 complexes are stable and immunogenic in mice transgenic for human CD4 and CCR5. They elicited anti-gp120 and anti-gp140 antibodies that inhibited an heterologous primary HIV-1 isolate (JR-FL) with two- to threefold higher neutralizing activity than those elicited by gp120 and gp140. The antibodies elicited by the complexes competed better with the antibodies X5 and CG10 but not with b12 for binding to gp120 and gp120-CD4 complexes compared to those elicited with gp140(120) alone. These findings suggest that stable purified Env-CD4-CCR5(CXCR4) complexes can be produced in relatively large amount sufficient for their further characterization that may help in the development of novel vaccines candidates. JF - Vaccine AU - Xiao, X AU - Phogat, S AU - Shu, Y AU - Phogat, A AU - Chow, Y-H AU - Wei, O L AU - Goldstein, H AU - Broder, C C AU - Dimitrov, D S AD - Laboratory of Experimental and Computational Biology, National Cancer Institute-Frederick, NIH, Bldg 469, Rm 246, P.O. Box B, Miller Drive, Frederick, MD 21702-1201, USA, dimitrov@ncifcrf.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 4275 EP - 4284 PB - Butterworth-Heinemann, 313 Washington St. Newton MA 02158 USA VL - 21 IS - 27-28 SN - 0264-410X, 0264-410X KW - CCR5 protein KW - CD4 antigen KW - CXCR4 protein KW - HIV-1 KW - Virology & AIDS Abstracts; Immunology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - F 06807:Active immunization KW - A 01097:Viruses KW - V 22003:AIDS: Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18873512?accountid=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=Vaccine&rft.atitle=Purified+complexes+of+HIV-1+envelope+glycoproteins+with+CD4+and+CCR5%28CXCR4%29%3A+Production%2C+characterization+and+immunogenicity&rft.au=Xiao%2C+X%3BPhogat%2C+S%3BShu%2C+Y%3BPhogat%2C+A%3BChow%2C+Y-H%3BWei%2C+O+L%3BGoldstein%2C+H%3BBroder%2C+C+C%3BDimitrov%2C+D+S&rft.aulast=Xiao&rft.aufirst=X&rft.date=2003-10-01&rft.volume=21&rft.issue=27-28&rft.spage=4275&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2FS0264-410X%2803%2900494-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0264-410X(03)00494-8 ER - TY - JOUR T1 - Rational Design of Drugs That Induce Human Immunodeficiency Virus Replication AN - 18826109; 5711859 AB - Drugs that induce human immunodeficiency virus type 1 (HIV-1) replication could be used in combination with highly active antiretroviral therapy (HAART) to reduce the size of the latent reservoir that is in part responsible for viral persistence. Protein kinase C (PKC) is a logical target for such drugs because it activates HIV-1 transcription through multiple mechanisms. Here we show that HIV-1 gene expression can be induced by potent synthetic analogues of the lipid second messenger diacylglycerol (DAG) synthesized on a five-member ring platform that reduces the entropy of binding relative to that of the more flexible DAG template. By varying the alkyl side chains of these synthetic DAG lactones, it was possible to maximize their potency and ability to render latently infected T cells sensitive to killing by an anti-HIV-1 immunotoxin while minimizing the side effects of CD4 and CXCR4 downregulation and tumor necrosis factor alpha upregulation. The two lead compounds, LMC03 and LMC07, regulated a series of PKC-sensitive genes involved in T-cell activation and induced viral gene expression in peripheral blood mononuclear cells from HIV-1-infected individuals. These studies demonstrate the potential for the rational design of agents that, in conjunction with HAART and HIV-specific toxins, can be used to decrease or eliminate the pool of latently infected reservoirs by forcing viral expression. JF - Journal of Virology AU - Hamer, D H AU - Bocklandt, S AU - McHugh, L AU - Chun, T-W AU - Blumberg, P M AU - Sigano, D M AU - Marquez, V E AD - Laboratory of Biochemistry, Bldg. 37, Rm. 6002, NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20892, DeanH@helix.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 10227 EP - 10236 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 77 IS - 19 SN - 0022-538X, 0022-538X KW - HIV-1 KW - diacylglycerol KW - highly active antiretroviral therapy KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W3 33372:Antiviral agents KW - W 30965:Miscellaneous, Reviews KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18826109?accountid=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=Rational+Design+of+Drugs+That+Induce+Human+Immunodeficiency+Virus+Replication&rft.au=Hamer%2C+D+H%3BBocklandt%2C+S%3BMcHugh%2C+L%3BChun%2C+T-W%3BBlumberg%2C+P+M%3BSigano%2C+D+M%3BMarquez%2C+V+E&rft.aulast=Hamer&rft.aufirst=D&rft.date=2003-10-01&rft.volume=77&rft.issue=19&rft.spage=10227&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/10.1128%2FJVI.77.19.10227-10236.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JVI.77.19.10227-10236.2003 ER - TY - JOUR T1 - Induction of murine ras oncogene peptide-specific T cell responses by immunization with plasmid DNA-based minigene vectors AN - 18824974; 5718365 AB - In a BALB/c mouse model, we have previously identified a ras oncogene peptide that contained both CD8 super(+) and CD4 super(+) T cell epitopes in a nested configuration. In this study, we developed several plasmid DNA minigene vectors encoding these determinants and examined whether they could induce antigen (Ag)- specific CD8 super(+) cytotoxic and CD4 super(+) lymphoproliferative responses. Furthermore, we compared two different immunization procedures, epidermal gene gun inoculation and intradermal (i.d.) injection of saline plasmid DNA, along with several approaches addressing different aspects of immune modulation. We demonstrated that each DNA plasmid induced the relevant Ag-specific cellular immune response. Gene gun inoculation was superior to that of needle injection for induction of the CTL response. Moreover, DNA plasmids containing both ras epitopes induced the highest CTL response, as compared with vector preparations containing only the CD8 super(+) epitope. These results suggested that a DNA plasmid expressing nested mutant ras epitope-specific CD4 super(+) and CD8 super(+) T cell epitopes can be processed in vivo to induce both subset-specific T cell responses, and that the addition of the helper epitope quantitatively improved the development of the CTL response, which may have implications for DNA-based anti-tumor immunotherapies. JF - Vaccine AU - Lindinger, P AU - Mostboeck, S AU - Hammerl, P AU - Hartl, A AU - Thalhamer, J AU - Abrams, SI AD - Immunology Group, Institute of Chemistry and Biochemistry, University of Salzburg, Salzburg, Austria, sa47z@nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 4285 EP - 4296 PB - Butterworth-Heinemann, 313 Washington St. Newton MA 02158 USA VL - 21 IS - 27-28 SN - 0264-410X, 0264-410X KW - BALB/c mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - F 06818:Cancer immunotherapy KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18824974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Induction+of+murine+ras+oncogene+peptide-specific+T+cell+responses+by+immunization+with+plasmid+DNA-based+minigene+vectors&rft.au=Lindinger%2C+P%3BMostboeck%2C+S%3BHammerl%2C+P%3BHartl%2C+A%3BThalhamer%2C+J%3BAbrams%2C+SI&rft.aulast=Lindinger&rft.aufirst=P&rft.date=2003-10-01&rft.volume=21&rft.issue=27-28&rft.spage=4285&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2FS0264-410X%2803%2900486-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0264-410X(03)00486-9 ER - TY - JOUR T1 - Antiretroviral Therapy-associated Serious and Life-threatening Toxicities. AN - 1859431985; 13678573 AB - In the late 1980s and early 1990s, when HIV/AIDS had become the leading cause of death in 25- to 44-year-old persons in the United States, it was acceptable to prescribe newer antiretroviral therapy such as zidovudine, which has significant bone marrow toxicities but can potentially improve patient survival. Although current antiretroviral therapy is not likely to eradicate HIV-1 infection, the advances in the use of combination antiretroviral therapy (including protease inhibitors and non-nucleoside reverse transcriptase inhibitors) have dramatically improved the overall survival, immune status, and productivity of HIV-infected individuals in developed countries. Instead of prevention and treatment of HIV-associated complications, many of the patients" clinic visits are focused on finding strategies to manage and prevent antiretroviral therapy-associated complications. Because only a few HIV-infected persons fulfilling stringent inclusion criteria were included in premarketing clinical trials and because the US Food and Drug Administration"s (FDA) accelerated approval process for antiretroviral therapy requires only 24-week safety and efficacy data, newly emerging and previously unrecognized adverse effects of antiretroviral therapy continue to surface when these drugs are administered to a larger patient population for a longer duration. Unfortunately, some of these adverse effects can be unpredictable and serious, and, if not recognized early and managed aggressively, can lead to fatality. This article reviews four of the most serious, life-threatening toxicities associated with antiretroviral therapy. JF - Current infectious disease reports AU - Pau, Alice K. AD - Clinical Center Pharmacy Department, National Institutes of Health, Department of Health and Human Services, Building 10, Room 1N257, Bethesda, MD 20892, USA. apau@niaid.nih.gov Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 429 EP - 438 VL - 5 IS - 5 SN - 1523-3847, 1523-3847 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859431985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+infectious+disease+reports&rft.atitle=Antiretroviral+Therapy-associated+Serious+and+Life-threatening+Toxicities.&rft.au=Pau%2C+Alice+K.&rft.aulast=Pau&rft.aufirst=Alice&rft.date=2003-10-01&rft.volume=5&rft.issue=5&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=Current+infectious+disease+reports&rft.issn=15233847&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2003-09-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Cohort Mortality Study of Workers Exposed to Chlorinated Organic Solvents in Taiwan AN - 18020977; 5980827 AB - A retrospective cohort mortality study based on standardized mortality ratios (SMRs) was conducted to investigate the possible association between exposure to chlorinated organic solvents and various types of cancer deaths. Vital status and causes of death of study subjects were determined from January 1, 1985 to December 31, 1997 by linking cohort data with the National Mortality Database. Person-year accumulation began on the date of entry to the cohort, or January 1, 1985 (whichever came later), and ended on the closing date of the study (December 31, 1997), if alive; or the date of death. This retrospective cohort study examined cancer mortality among 86,868 workers at an electronics factory in the northern Taiwan. Using various durations of employment and latency and adjusting for age and calendar year, no significantly elevated SMR was found for any cancer in either male or female exposed workers when compared with the general Taiwanese population. In particular, the risk of female breast cancer was not found to be increased. Although ovarian cancer suggested an upward trend when analyzed by length of employment, ovarian cancer risk for the entire female cohort was not elevated. It is concluded that this study provided no evidence that exposure to chlorinated organic solvents was associated with human cancer risk. JF - Annals of Epidemiology AU - Chang, Yung-Ming AU - Tai, Chi-Fu AU - Yang, Sweo-Chung AU - Chen, Chiou-Jong AU - Shih, Tung-Sheng AU - Lin, R S AU - Liou, Saou-Hsing AD - 161 Ming-Chun East Road, Sec. 6, P.O. Box 90048-509, Rm. 4333, Nei-Hu, Taipei, Taiwan, 114, Republic of China, shliou@ndmctsgh.edu.tw Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 652 EP - 660 VL - 13 IS - 9 SN - 1047-2797, 1047-2797 KW - Health & Safety Science Abstracts; Risk Abstracts KW - Taiwan KW - Factories KW - Electronics industry KW - Occupational exposure KW - Mortality KW - Solvents KW - Cancer KW - R2 23080:Industrial and labor KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18020977?accountid=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=Annals+of+Epidemiology&rft.atitle=A+Cohort+Mortality+Study+of+Workers+Exposed+to+Chlorinated+Organic+Solvents+in+Taiwan&rft.au=Chang%2C+Yung-Ming%3BTai%2C+Chi-Fu%3BYang%2C+Sweo-Chung%3BChen%2C+Chiou-Jong%3BShih%2C+Tung-Sheng%3BLin%2C+R+S%3BLiou%2C+Saou-Hsing&rft.aulast=Chang&rft.aufirst=Yung-Ming&rft.date=2003-10-01&rft.volume=13&rft.issue=9&rft.spage=652&rft.isbn=&rft.btitle=&rft.title=Annals+of+Epidemiology&rft.issn=10472797&rft_id=info:doi/10.1016%2FS1047-2797%2803%2900038-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Taiwan; Solvents; Cancer; Mortality; Occupational exposure; Factories; Electronics industry DO - http://dx.doi.org/10.1016/S1047-2797(03)00038-3 ER - TY - JOUR T1 - Methods for on-chip protein analysis AN - 17853780; 5707669 AB - The unambiguous identification of peptides/proteins is crucial for the definition of the proteome. Using ProteinChip Array technology also known as surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS), we developed experimental protocols and probed test conditions required for the protein identification on ProteinChip surfaces. We were able to directly digest peptides/proteins on-chip surfaces by specific proteases, such as trypsin, and to obtain the peptide mass fingerprint of the sample under investigation by its direct analysis on a simple laser desorption/ionization mass spectrometer. Furthermore, tandem mass spectrometry was performed on several of the resulting tryptic peptides by using collision quadrupole time of flight (Qq-TOF) MS/MS via the ProteinChip interface, thus allowing the unambiguous identification of the protein(s) within the sample. In addition, we were able to identify the C-terminal sequence of peptides by their digestion with carboxypeptidase Y directly on ProteinChip surfaces coupled with SELDI-TOF MS analysis of the resulting peptide mass ladders employing the instrument's protein ladder sequence software. Moreover, the removal of up to nine amino acid residues from the C-terminal end of a peptide extends the functional range of Qq-TOF MS/MS sequence determination to over 3000 m/z. The utility of these procedures for the proteome exploration are discussed. JF - Analytical Biochemistry AU - Caputo, E AU - Moharram, R AU - Martin, B M AD - Unit on Molecular Structures, LNT, NIMH, NIH, DHHS, 10 Center Drive, Bldg. 10 3N309, Bethesda, MD 20892-1262, USA, martinb@irp.nimh.nih.gov Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 116 EP - 124 PB - Academic Press, Inc., 525 B St. Ste. 1900 San Diego CA 92101-4495 USA, [mailto:apsubs@acad.com] VL - 321 IS - 1 SN - 0003-2697, 0003-2697 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Desorption KW - Trypsin KW - Mass spectroscopy KW - Digestion KW - Computer programs KW - software KW - Carboxypeptidase C KW - Exploration KW - Tryptic peptides KW - Proteinase KW - Lasers KW - Ionization KW - Amino acid sequence KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17853780?accountid=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=Analytical+Biochemistry&rft.atitle=Methods+for+on-chip+protein+analysis&rft.au=Caputo%2C+E%3BMoharram%2C+R%3BMartin%2C+B+M&rft.aulast=Caputo&rft.aufirst=E&rft.date=2003-10-01&rft.volume=321&rft.issue=1&rft.spage=116&rft.isbn=&rft.btitle=&rft.title=Analytical+Biochemistry&rft.issn=00032697&rft_id=info:doi/10.1016%2FS0003-2697%2803%2900361-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Amino acid sequence; Mass spectroscopy; Lasers; Desorption; Proteinase; Tryptic peptides; Exploration; Computer programs; Digestion; Ionization; Trypsin; software; Carboxypeptidase C DO - http://dx.doi.org/10.1016/S0003-2697(03)00361-0 ER - TY - JOUR T1 - Metabolic fate of exogenous super(15)NH sub(4)Cl in the gulf toadfish (Opsanus beta) AN - 17669100; 5858100 AB - This study was undertaken to determine whether gulf toadfish (Opsanus beta) could metabolize ammonia from their environment into other, less toxic products. To this end, gulf toadfish were exposed to 3.8 mM super(15)NH sub(4)Cl in seawater for 24 and 48 h. Liver, kidney, gill, brain and muscle samples were analyzed for distribution of super(15)N within the tissue and among various nitrogen-containing metabolites (ammonia, amino-N, glutamine-N, urea and protein). The data reported here show that the toadfish can indeed take up and metabolize ammonia. Analysis of individual metabolic products of ammonia indicates that the toadfish can convert this toxic chemical into other less toxic metabolites. Ammonia enrichment is significantly different over controls in the kidney, brain and muscle. Urea enrichment is most significant in the brain, with less significant enrichment occurring in the liver and muscle. While accumulation of ammonia into an amino acid pool was not a significant metabolic fate, protein synthesis was significantly enriched in all tissues (with the highest levels occurring in the gill) indicating that amino acid synthesis may be a pathway of ammonia detoxification en route to protein synthesis, and that environmental ammonia can be 'fixed' into protein. Finally, it was found that glutamine-N synthesis occurs at significant levels in the liver, brain and muscle. JF - Comparative Biochemistry and Physiology, Part C: Toxicology & Pharmacology AU - Rodicio, L P AU - da Silveira Lobo Sternberg, L AU - Walsh, P J 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 Cswy, Miami, FL 33149, USA Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 157 EP - 164 VL - 136 IS - 2 SN - 1532-0456, 1532-0456 KW - Marine fish KW - Toadfishes KW - Oceanic Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources KW - Marine KW - Q1 01346:Physiology, biochemistry, biophysics KW - O 4020:Pollution - Organisms/Ecology/Toxicology KW - Q5 01504:Effects on organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17669100?accountid=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=Comparative+Biochemistry+and+Physiology%2C+Part+C%3A+Toxicology+%26+Pharmacology&rft.atitle=Metabolic+fate+of+exogenous+super%2815%29NH+sub%284%29Cl+in+the+gulf+toadfish+%28Opsanus+beta%29&rft.au=Rodicio%2C+L+P%3Bda+Silveira+Lobo+Sternberg%2C+L%3BWalsh%2C+P+J&rft.aulast=Rodicio&rft.aufirst=L&rft.date=2003-10-01&rft.volume=136&rft.issue=2&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Comparative+Biochemistry+and+Physiology%2C+Part+C%3A+Toxicology+%26+Pharmacology&rft.issn=15320456&rft_id=info:doi/10.1016%2FS1532-0456%2803%2900196-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Marine DO - http://dx.doi.org/10.1016/S1532-0456(03)00196-0 ER - TY - JOUR T1 - Characterization of atmospheric PM sub(10) and related chemical species in southern Taiwan during the episode days AN - 16156227; 5673969 AB - The concentrations of atmospheric PM sub(10) on days with episodes of pollution were examined at four different sampling sites (CC, DL, LY, and HK) in southern Taiwan. The related to particulates water-soluble ionic species (Na super(+), K super(+), Mg super(2+), Ca super(2+), NH sub(4) super(+), Cl super(-), NO sub(3) super(-), SO sub(4) super(2-)), carbonaceous species (EC and OC) and metallic species (Zn, Ni, Pb, Fe, Mn, Al, Si, V) were also analyzed. On the episode days of this study, the PM sub(10) mass concentration ranged from 155 to 210 mu g m super(-3), from 150 to 208 mu g m super(-3), from 182 to 249 mu g m super(-3), and from 166 to 228 mu g m super(-3) at CC, DL, LY, and HK, respectively. The results indicate that the dominant water-soluble species were SO sub(4) super(2-), NO sub(3) super(-), NH sub(4) super(+), and Cl super(-) at the four sampling sites on these days. Moreover, the high sulfate and nitrate conversion values (SOR and NOR) presented herein suggest that secondary formations from SO sub(2) to SO sub(4) super(2-) and from NO sub(2) to NO sub(3) super(-) are present in significant quantities in the atmosphere of southern Taiwan on episode days. In particular, high SOR and NOR verified that both SO sub(4) super(2-) and NO sub(3) super(-) dominated the increase of atmospheric PM sub(10) concentration in southern Taiwan on episode days. JF - Chemosphere AU - Chen, S-J AU - Hsieh, L-T AU - Tsai, C-C AU - Fang, G-C AD - Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Nei Pu 912, Ping Tung 91201, Taiwan, chensj@mail.npust.edu.tw Y1 - 2003/10// PY - 2003 DA - Oct 2003 SP - 29 EP - 41 PB - Elsevier Science Ltd., Pergamon, P.O. Box 800 Kidlington Oxford OX5 1DX UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 53 IS - 1 SN - 0045-6535, 0045-6535 KW - Meteorological & Geoastrophysical Abstracts; Pollution Abstracts KW - PM10 KW - Episode day KW - Water-soluble ions KW - EC KW - OC KW - Taiwan KW - Atmospheric pollution KW - Chemical speciation KW - Atmospheric chemistry KW - Air sampling KW - Urban atmospheric pollution KW - Particulates KW - Particulate atmospheric pollution KW - M2 551.510.42:Air Pollution (551.510.42) KW - P 0000:AIR POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/16156227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemosphere&rft.atitle=Characterization+of+atmospheric+PM+sub%2810%29+and+related+chemical+species+in+southern+Taiwan+during+the+episode+days&rft.au=Chen%2C+S-J%3BHsieh%2C+L-T%3BTsai%2C+C-C%3BFang%2C+G-C&rft.aulast=Chen&rft.aufirst=S-J&rft.date=2003-10-01&rft.volume=53&rft.issue=1&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Chemosphere&rft.issn=00456535&rft_id=info:doi/10.1016%2FS0045-6535%2803%2900360-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2004-06-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Atmospheric pollution; Urban atmospheric pollution; Particulate atmospheric pollution; Chemical speciation; Atmospheric chemistry; Air sampling; Particulates; Taiwan DO - http://dx.doi.org/10.1016/S0045-6535(03)00360-6 ER - TY - JOUR T1 - Substitution of the structural genes of dengue virus type 4 with those of type 2 results in chimeric vaccine candidates which are attenuated for mosquitoes, mice, and rhesus monkeys AN - 1500759431; 19045962 AB - Antigenic chimeric viruses in which the structural genes of dengue virus type 4 (DEN4) have been replaced with those derived from dengue virus type 2 (DEN2) have been created and evaluated as a first step in generating a live attenuated tetravalent dengue virus vaccine. Specifically, the capsid, membrane precursor, and envelope (CME) or the membrane precursor and envelope (ME) gene regions of DEN2 were substituted for the corresponding genes of wild-type rDEN4 or vaccine candidate rDEN4 Delta 30 which contains a 30 nucleotide deletion in the 3' untranslated region. The two DEN2/4 chimeric viruses lacking the Delta 30 mutation were highly attenuated in tumor-bearing SCID-HuH-7 mice, mosquitoes, and rhesus monkeys, indicating chimerization with either the CME or ME regions lead to attenuation. In mosquitoes and SCID-HuH-7 mice, addition of the Delta 30 mutation to the chimeric viruses resulted in comparable or only slightly increased levels of attenuation. In rhesus monkeys, addition of the Delta 30 mutation rendered the CME chimeric virus non-infectious, indicating that the attenuation resulting from chimerization and the Delta 30 mutation were additive for these animals. In contrast, the attenuation in rhesus monkeys of ME chimeric virus was not significantly modified by the addition of the Delta 30 mutation. The satisfactory level of attenuation and immunogenicity achieved by the ME containing DEN2/4 Delta 30 chimeric virus, as well as its very low infectivity for mosquitoes, make it a vaccine candidate suitable for evaluation in phase I clinical trials. JF - Vaccine AU - Whitehead, Stephen S AU - Hanley, Kathryn A AU - Blaney, Joseph E, Jr AU - Gilmore, Lara E AU - Elkins, William R AU - Murphy, Brian R AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Room 6515, Building 50, 50 South Drive, Bethesda, MD 20892-8007, USA Y1 - 2003/10// PY - 2003 DA - October 2003 SP - 4307 EP - 4316 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 21 IS - 27 SN - 0264-410X, 0264-410X KW - Genetics Abstracts; ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Virology & AIDS Abstracts; Immunology Abstracts KW - Dengue KW - Chimerization KW - Vaccination KW - Capsids KW - ME gene KW - Mutations KW - Viruses KW - Disease control KW - Culicidae KW - Clinical trials KW - Nucleotides KW - Public health KW - Infectivity KW - Gene deletion KW - Envelopes KW - Genes KW - Immunogenicity KW - Macaca mulatta KW - Vaccines KW - Dengue virus type 2 KW - Mutation KW - Aquatic insects KW - Dengue virus type 4 KW - G 07720:Immunogenetics KW - Q1 08626:Food technology KW - V 22350:Immunology KW - F 06905:Vaccines KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1500759431?accountid=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=Vaccine&rft.atitle=Substitution+of+the+structural+genes+of+dengue+virus+type+4+with+those+of+type+2+results+in+chimeric+vaccine+candidates+which+are+attenuated+for+mosquitoes%2C+mice%2C+and+rhesus+monkeys&rft.au=Whitehead%2C+Stephen+S%3BHanley%2C+Kathryn+A%3BBlaney%2C+Joseph+E%2C+Jr%3BGilmore%2C+Lara+E%3BElkins%2C+William+R%3BMurphy%2C+Brian+R&rft.aulast=Whitehead&rft.aufirst=Stephen&rft.date=2003-10-01&rft.volume=21&rft.issue=27&rft.spage=4307&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2FS0264-410X%2803%2900488-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-02-01 N1 - Last updated - 2016-10-12 N1 - SubjectsTermNotLitGenreText - Genes; Mutations; Viruses; Disease control; Vaccines; Aquatic insects; Nucleotides; Public health; Capsids; ME gene; Gene deletion; Infectivity; Envelopes; Immunogenicity; Clinical trials; Mutation; Macaca mulatta; Culicidae; Dengue virus type 2; Dengue virus type 4 DO - http://dx.doi.org/10.1016/S0264-410X(03)00488-2 ER - TY - JOUR T1 - The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. AN - 75748027; 14504405 AB - The role of the hepatitis C virus (HCV) p7 protein in the virus life cycle is not known. Previous in vitro data indicated that this 63-aa polypeptide is located in the endoplasmic reticulum and has two transmembrane domains (TMDs) connected by a cytoplasmic loop; the amino- and carboxyl-terminal tails are oriented toward the endoplasmic reticulum lumen. Furthermore, recent in vitro studies suggested that HCV p7 could function as a virus-encoded ion channel. It might therefore be a relevant target for future drug development. We studied the role of HCV p7 in vivo. Because HCV does not replicate efficiently in cell culture, we mutagenized p7 of an infectious genotype 1a cDNA clone and tested RNA transcripts of each mutant for infectivity in chimpanzees by intrahepatic transfection. Appropriate processing of mutant polypeptides was confirmed by studies in transfected mammalian cells. Mutants with deletions of all or part of p7 and a mutant with substitutions of two conserved residues in the cytoplasmic loop were not viable. Thus, p7 is essential for infectivity of HCV. A chimera in which the p7 of the 1a clone was replaced with p7 from an infectious genotype 2a clone also was not viable. This finding suggests a genotype-specific interaction between p7 and other genomic regions. To define which portions of p7 played the most significant role for this interaction, we tested three chimeras with the 1a backbone in which only specific domains of p7 had the 2a sequence. A p7 chimera with 2a tails and TMDs and the 1a cytoplasmic loop was not viable. A mutant with 2a tails and cytoplasmic loop and 1a TMDs also was not viable. However, a p7 chimera with 2a TMDs and cytoplasmic loop and 1a tails was viable. The transfected chimpanzee became viremic at week 2, and recovered viruses had the chimeric sequence. These data indicate that the amino- and/or carboxyl-terminal intraluminal tails of p7 contain sequences with genotype-specific function. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Sakai, Akito AU - Claire, Marisa St AU - Faulk, Kristina AU - Govindarajan, Sugantha AU - Emerson, Suzanne U AU - Purcell, Robert H AU - Bukh, Jens AD - Hepatitis Viruses and Molecular Hepatitis Sections, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/09/30/ PY - 2003 DA - 2003 Sep 30 SP - 11646 EP - 11651 VL - 100 IS - 20 SN - 0027-8424, 0027-8424 KW - Viral Proteins KW - 0 KW - p7 protein, Hepatitis C virus KW - Index Medicus KW - Virulence KW - Genotype KW - Animals KW - Humans KW - Genetic Vectors KW - Cell Line KW - Pan troglodytes KW - Mutagenesis KW - Viral Proteins -- genetics KW - Hepacivirus -- pathogenicity KW - Hepacivirus -- genetics KW - Viral Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75748027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+p7+polypeptide+of+hepatitis+C+virus+is+critical+for+infectivity+and+contains+functionally+important+genotype-specific+sequences.&rft.au=Sakai%2C+Akito%3BClaire%2C+Marisa+St%3BFaulk%2C+Kristina%3BGovindarajan%2C+Sugantha%3BEmerson%2C+Suzanne+U%3BPurcell%2C+Robert+H%3BBukh%2C+Jens&rft.aulast=Sakai&rft.aufirst=Akito&rft.date=2003-09-30&rft.volume=100&rft.issue=20&rft.spage=11646&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 - 2003-11-25 N1 - Date created - 2003-10-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 2002 Apr;76(8):4034-43 [11907242] J Virol. 2002 Apr;76(8):3720-30 [11907211] RNA. 2002 Jun;8(6):824-41 [12088154] J Biol Chem. 2002 Sep 6;277(36):33228-34 [12082096] Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14416-21 [12391335] FEBS Lett. 2003 Jan 30;535(1-3):34-8 [12560074] J Virol. 2003 May;77(10):6050-4 [12719596] Proc Natl Acad Sci U S A. 2003 May 13;100(10):6104-8 [12719519] Hepatology. 2003 Jun;37(6):1359-67 [12774015] J Virol. 1993 Mar;67(3):1385-95 [7679746] J Virol. 1994 Apr;68(4):2731-4 [8139048] J Virol. 1994 Aug;68(8):5063-73 [7518529] J Virol. 1994 Oct;68(10):6147-60 [8083956] J Virol. 1994 Oct;68(10):6215-22 [8083961] Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15394-9 [8986822] Hepatology. 1997 Jun;25(6):1527-38 [9185778] Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8738-43 [9238047] Virology. 1998 Apr 25;244(1):161-72 [9581788] J Infect Dis. 1998 Oct;178(4):1193-7 [9806059] Virology. 1999 Sep 15;262(1):250-63 [10489358] Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2291-5 [10051634] Science. 1999 Jul 2;285(5424):110-3 [10390360] Curr Top Microbiol Immunol. 2000;242:55-84 [10592656] J Virol. 2000 Feb;74(4):2046-51 [10644379] J Virol. 2000 Oct;74(20):9498-506 [11000219] Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13318-23 [11078521] Science. 2000 Dec 8;290(5498):1972-4 [11110665] J Virol. 2001 Jun;75(12):5656-62 [11356973] J Virol. 2002 Feb;76(3):1391-9 [11773413] Protein Sci. 2002 Mar;11(3):546-57 [11847278] Biochim Biophys Acta. 2002 Mar 19;1561(1):27-45 [11988179] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hydrolysis of RNA/DNA hybrids containing nonpolar pyrimidine isosteres defines regions essential for HIV type 1 polypurine tract selection. AN - 75729408; 12972638 AB - Both x-ray crystallography and chemical footprinting indicate that bases of the HIV type 1 (HIV-1) polypurine tract (PPT)-containing RNA/DNA hybrid deviate from standard Watson-Crick base pairing. However, the contribution of these structural anomalies to the accuracy of plus-strand primer selection by HIV-1 reverse transcriptase is not immediately clear. To address this issue, DNA templates harboring single and pairwise non-hydrogen-bonding isosteres of cytosine (2-fluoro-4-methylbenzene deoxyribonucleoside) and thymine (2,4-difluoro-5-methylbenzene deoxyribonucleoside) were synthesized and hybridized to PPT-containing RNA primers as a means of locally removing hydrogen bonding and destabilizing paired structure. Cleavage of these hybrids was examined with p66/p51 HIV-1 reverse transcriptase and a mutant carrying an alteration in the p66 RNase H primer shown to specifically impair PPT processing. Analog insertion within the PPT (rG):(dC) and central (rA):(dT) tracts repositioned the RNase H domain such that the RNA/DNA hybrid was cleaved 3-4 bp from the site of insertion, a distance corresponding closely to the spatial separation between the catalytic center and RNase H primer grip. However, PPT processing was significantly impaired when the junction between these tracts was substituted. Substitutions within the upstream (rA):(dT) tract, where maximum distortion had previously been observed, destroyed PPT processing. Collectively, our scanning mutagenesis approach implicates multiple regions of the PPT in the accuracy with which it is excised from (+) U3 RNA and DNA, and also provides evidence for close cooperation between the RNase H primer grip and catalytic center in achieving this cleavage. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Rausch, Jason W AU - Qu, Jin AU - Yi-Brunozzi, Hye Young AU - Kool, Eric T AU - Le Grice, Stuart F J AD - HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2003/09/30/ PY - 2003 DA - 2003 Sep 30 SP - 11279 EP - 11284 VL - 100 IS - 20 SN - 0027-8424, 0027-8424 KW - DNA Primers KW - 0 KW - Purines KW - Pyrimidines KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Index Medicus KW - Base Sequence KW - HIV Reverse Transcriptase -- metabolism KW - Nucleic Acid Hybridization KW - Hydrolysis KW - Purines -- metabolism KW - HIV-1 -- metabolism KW - RNA -- metabolism KW - DNA -- metabolism KW - Pyrimidines -- metabolism KW - HIV-1 -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75729408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hydrolysis+of+RNA%2FDNA+hybrids+containing+nonpolar+pyrimidine+isosteres+defines+regions+essential+for+HIV+type+1+polypurine+tract+selection.&rft.au=Rausch%2C+Jason+W%3BQu%2C+Jin%3BYi-Brunozzi%2C+Hye+Young%3BKool%2C+Eric+T%3BLe+Grice%2C+Stuart+F+J&rft.aulast=Rausch&rft.aufirst=Jason&rft.date=2003-09-30&rft.volume=100&rft.issue=20&rft.spage=11279&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 - 2003-11-25 N1 - Date created - 2003-10-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Biochem. 2002;71:191-219 [12045095] J Biol Chem. 2002 May 10;277(19):16689-96 [11875059] J Biol Chem. 2002 Aug 30;277(35):31673-8 [12077143] Nucleic Acids Res. 2002 Sep 15;30(18):4061-7 [12235390] J Virol. 2003 May;77(9):5275-85 [12692229] J Mol Biol. 1989 Aug 5;208(3):445-56 [2477553] J Virol. 1992 Jan;66(1):367-73 [1370087] J Biol Chem. 1993 Mar 25;268(9):6221-7 [7681062] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6320-4 [7687065] J Mol Biol. 1996 Feb 16;256(1):108-25 [8609604] J Virol. 2000 May;74(10):4755-64 [10775614] J Biol Chem. 2000 May 19;275(20):15025-33 [10747890] Biochemistry. 2000 Oct 24;39(42):12979-88 [11041863] Biochemistry. 2000 Nov 28;39(47):14603-10 [11087416] EMBO J. 2001 Mar 15;20(6):1449-61 [11250910] Biochemistry. 2001 Mar 13;40(10):3215-21 [11258938] J Virol. 2001 Jul;75(14):6537-46 [11413321] J Biol Chem. 2001 Dec 7;276(49):46225-9 [11641390] Biochemistry. 2002 Apr 16;41(15):4856-65 [11939780] J Virol. 1996 Aug;70(8):5288-96 [8764039] J Biol Chem. 1997 Mar 28;272(13):8602-10 [9079691] Nat Struct Biol. 1997 Mar;4(3):194-7 [9164459] EMBO J. 1998 Jul 1;17(13):3766-74 [9649446] Nucleosides Nucleotides. 1998 Apr;17(4):831-41 [9708337] Nat Struct Biol. 1998 Nov;5(11):954-9 [9808039] Science. 1998 Nov 27;282(5394):1669-75 [9831551] Biopolymers. 1998;48(1):3-17 [9846123] J Biol Chem. 1999 May 21;274(21):15066-72 [10329711] J Biol Chem. 1999 Jul 9;274(28):19885-93 [10391934] Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9515-20 [12093908] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Borrelia oxidative stress response regulator, BosR: A distinctive Zn-dependent transcriptional activator AN - 18884309; 5738575 AB - The ability of a pathogen to cause infection depends on successful colonization of the host, which, in turn, requires adaptation to various challenges presented by that host. For example, host immune cells use a variety of mechanisms to control infection by bacterial pathogens, including the production of bactericidal reactive oxygen species. Prokaryotic and eukaryotic cells have developed ways of protecting themselves against this oxidative damage; for instance, Borrelia burgdorferi alters the expression of oxidative-stress-related proteins, such as a Dps/Dpr homolog NapA (BB0690), in response to increasing levels of oxygen and reactive oxygen species. These stress-related genes appear to be regulated by a putative metal-dependent DNA- binding protein (BB0647) that has 50.7% similarity to the peroxide-specific stress response repressor of Bacillus subtilis, PerR. We overexpressed and purified this protein from Escherichia coli and designated it Borrelia oxidative stress regulator, BosR. BosR bound to a 50-nt region 180 bp upstream of the napA transcriptional start site and required DTT and Zn super(2+) for optimal binding. Unlike the Bacillus subtilis PerR repressor, BosR did not require Fe super(2+) and Mn super(2+) for binding, and oxidizing agents, such as t- butyl peroxide, enhanced, not eliminated, BosR binding to the napA promoter region. Surprisingly, transcriptional fusion analysis indicated that BosR exerted a positive regulatory effect on napA that is inducible with t- butyl peroxide. On the basis of these data, we propose that, despite the similarity to PerR, BosR functions primarily as a transcriptional activator, not a repressor of oxidative stress response, in B. burgdorferi. JF - Proceedings of the National Academy of Sciences, USA AU - Boylan, JA AU - Posey, JE AU - Gherardini, F C AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 904 South 4th Street, Hamilton, MT 59840, fgherardini@niaid.nih.gov Y1 - 2003/09/30/ PY - 2003 DA - 2003 Sep 30 SP - 11684 EP - 11689 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 20 SN - 0027-8424, 0027-8424 KW - BosR protein KW - PerR protein KW - T-Butyl peroxide KW - napA gene KW - t-butyl peroxide KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - MICROBIOLOGY KW - Bacillus subtilis KW - Reactive oxygen species KW - Borrelia burgdorferi KW - Oxidative stress KW - Zinc KW - Transcription activators KW - J 02726:RNA and ribosomes KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18884309?accountid=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=Borrelia+oxidative+stress+response+regulator%2C+BosR%3A+A+distinctive+Zn-dependent+transcriptional+activator&rft.au=Boylan%2C+JA%3BPosey%2C+JE%3BGherardini%2C+F+C&rft.aulast=Boylan&rft.aufirst=JA&rft.date=2003-09-30&rft.volume=100&rft.issue=20&rft.spage=11684&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.2032956100 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Reactive oxygen species; Oxidative stress; Zinc; Transcription activators; Bacillus subtilis; Borrelia burgdorferi DO - http://dx.doi.org/10.1073/pnas.2032956100 ER - TY - JOUR T1 - Cofactor Determination and Spectroscopic Characterization of the Selenium-Dependent Purine Hydroxylase from Clostridium purinolyticum AN - 17972450; 5914174 AB - Purine hydroxylase (PH) from Clostridium purinolyticum contains a labile selenium cofactor and belongs to a class of enzymes known as the selenium-dependent molybdenum hydroxylases. The presence of approximately 1.1 mol of molybdenum, 0.87 mol of selenium, and 3.3 mol of iron per mol of PH was determined by atomic absorption spectroscopy. Enzyme preparations with lower than stoichiometric amounts of selenium exhibited correspondingly lower hydroxylase activities. Bound FAD, 1 mol per mol enzyme, was confirmed by UV-vis and fluorescence spectroscopy. CMP, released by acid hydrolysis, indicated the presence of a molybdopterin cytosine dinucleotide cofactor. The fully active PH utilized NADP super(+) as an electron acceptor, and kinetic analysis revealed an optimal k sub(cat) of 412 s super(-1) using hypoxanthine as the hydroxylase substrate. Xanthine, NAD super(+), and NADPH had no significant effect on this reaction rate. A selenium-independent NADPH oxidase activity was exhibited by native PH. Electron paramagnetic resonance spectroscopy revealed the presence of a Mo(V) desulfo signal, FAD radical, and 2Fe-2S centers in hypoxanthine-reduced PH. No hyperfine coupling of selenium, using super(77)Se isotope-enriched PH, was observed in any of the EPR active signals studied. The appearance of the desulfo signal suggests that the ligands of Mo in selenium-dependent molybdenum hydroxylases are different from the well-studied mammalian xanthine oxidoreductases (XOR) and aldehyde oxidoreductases (AOR) and suggests a unique role for Se in catalysis. JF - Biochemistry (Washington) AU - Self, W T AU - Wolfe, MD AU - Stadtman, T C AD - Laboratory of Biochemistry, National Heart, Lung and Blood Institute, National Institutes of Health, 50 South Drive MSC 8012, Bethesda, MD 20892-8012, USA Y1 - 2003/09/30/ PY - 2003 DA - 2003 Sep 30 SP - 11382 EP - 11390 VL - 42 IS - 38 SN - 0006-2960, 0006-2960 KW - Microbiology Abstracts B: Bacteriology KW - xanthine oxidoreductase KW - Xanthine KW - Molybdenum KW - NADH KW - purine hydroxylase KW - Spectroscopy KW - Selenium KW - Cofactors KW - NAD KW - Clostridium purinolyticum KW - oxidoreductase KW - Aldehydes KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17972450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Cofactor+Determination+and+Spectroscopic+Characterization+of+the+Selenium-Dependent+Purine+Hydroxylase+from+Clostridium+purinolyticum&rft.au=Self%2C+W+T%3BWolfe%2C+MD%3BStadtman%2C+T+C&rft.aulast=Self&rft.aufirst=W&rft.date=2003-09-30&rft.volume=42&rft.issue=38&rft.spage=11382&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi030136k LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Clostridium purinolyticum; xanthine oxidoreductase; Selenium; Cofactors; Spectroscopy; oxidoreductase; Aldehydes; Xanthine; NAD; NADH; Molybdenum; purine hydroxylase DO - http://dx.doi.org/10.1021/bi030136k ER - TY - JOUR T1 - Small-molecule cyclin-dependent kinase modulators. AN - 75757946; 14528286 AB - Aberrations in cell cycle progression occur in the majority of human malignancies. The main pathway affected is the retinoblastoma (Rb) pathway. The tumor suppressor gene Rb is an important component in the G(1)/S transition and its function is abnormal in most human neoplasms. Loss in Rb function occurs by the hyperactivation of the cyclin-dependent kinases (cdk's). Therefore, modulation of cdk's may have an important use for the therapy and prevention of human neoplasms. Efforts to obtain small-molecule cdk modulators yielded two classes of modulators: direct and indirect modulators. Direct cdk modulators are small molecules that specifically target the ATP binding site of cdk's. Examples for this group include flavopiridol, roscovitine and BMS-387032. In contrast, indirect cdk modulators affect cdk function due to modulation of upstream pathways required for cdk activation. Some examples include perifosine, lovastatin, and UCN-01. The first example of a direct small-molecule cdk modulator tested in the clinic, flavopiridol, is a pan-cdk inhibitor that not only promotes cell cycle arrest but also halts transcriptional elongation, promotes apoptosis, induces differentiation, and has antiangiogenic properties. Clinical trials with this agent were performed with at least three different schedules of administration: 1-, 24- and 72-h infusions. The main toxicities for infusions >/=24-h are secretory diarrhea and proinflammatory syndrome. In addition, patients receiving shorter infusions have nausea/vomiting and neutropenia. A phase II trial of patients with advanced non-small-cell lung carcinoma using the 72-h infusion every 2 weeks was recently completed. The median overall survival for the 20 patients who received treatment was 7.5 months, a survival similar to that obtained in a randomized trial of four chemotherapy regimens containing platinum analogues in combination with taxanes or gemcitabine, or with gefitinib, a recently approved EGFR inhibitor for the treatment of advanced lung cancer. Based on these encouraging results, a phase III trial comparing standard combination chemotherapy versus combination chemotherapy plus flavopiridol is currently under investigation. The second example of direct small-molecule cdk modulator tested in clinical trials is UCN-01 (7-hydroxystaurosporine). UCN-01 has interesting preclinical features: it inhibits Ca(2+)-dependent PKCs, promotes apoptosis, arrests cell cycle progression at G(1)/S, and abrogates checkpoints upon DNA damage. The first phase I trial of UCN-01 demonstrated a very prolonged half-life. Based on this novel feature, UCN-01 is administered as a 72-h continuous infusion every 4 weeks (in second and subsequent cycles UCN-01 is administered as a 36-h infusion). Other shorter schedules (i.e. 3 h) are being tested. Dose-limiting toxicities include nausea/vomiting, hypoxemia, and insulin-resistant hyperglycemia. Combination trials with cisplatin and other DNA-damaging agents are being tested. Recently, phase I trials with two novel small-molecule cdk modulators, BMS 387032 and R-Roscovitine (CYC202), have commenced with good tolerability. In summary, novel small-molecule cdk modulators are being tested in the clinic with interesting results. Although these small molecules are directed towards a very prevalent cause of carcinogenesis, we need to test them in advanced clinical trials to determine the future of this class of agents for the prevention and therapy of human malignancies. JF - Oncogene AU - Senderowicz, Adrian M AD - Molecular Therapeutics Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4330, USA. sendero@helix.nih.gov Y1 - 2003/09/29/ PY - 2003 DA - 2003 Sep 29 SP - 6609 EP - 6620 VL - 22 IS - 42 SN - 0950-9232, 0950-9232 KW - Enzyme Inhibitors KW - 0 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Genes, Tumor Suppressor KW - Humans KW - Cell Cycle -- physiology KW - Clinical Trials as Topic KW - Cell Division -- physiology KW - Cell Cycle -- genetics KW - Cell Division -- genetics KW - Cyclin-Dependent Kinases -- genetics KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Enzyme Inhibitors -- therapeutic use KW - Genes, Retinoblastoma KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75757946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Small-molecule+cyclin-dependent+kinase+modulators.&rft.au=Senderowicz%2C+Adrian+M&rft.aulast=Senderowicz&rft.aufirst=Adrian&rft.date=2003-09-29&rft.volume=22&rft.issue=42&rft.spage=6609&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-12 N1 - Date created - 2003-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation site interdependence of human p53 post-translational modifications in response to stress. AN - 75700511; 12860987 AB - Modification-specific antibodies were used to characterize the phosphorylation and acetylation of human p53 in response to genotoxic (UV, IR, and adriamycin) and non-genotoxic (PALA, taxol, nocodazole) stress in cultured human cells at 14 known modification sites. In A549 cells, phosphorylation or acetylation was induced at most sites by the three DNA damage-inducing agents, but significant differences between agents were observed. IR-induced phosphorylation reached a maximum 2 h after treatment and returned to near pretreatment levels by 72 h; UV light and adriamycin induced a less rapid but more robust and prolonged p53 phosphorylation, which reached a maximum between 8 and 24 h, but persisted (UV) even 96 h after treatment. Ser33, Ser37, Ser46, and Ser392 were more efficiently phosphorylated after exposure to UV light than after IR. The non-genotoxic agents PALA, taxol and nocodazole induced p53 accumulation and phosphorylation at Ser6, Ser33, Ser46, and Ser392. Some phosphorylation at Ser15 also was observed. Modifications occurred similarly in the HCT116 human colon carcinoma cell line. Analysis of single site mutant p53s indicated clear interdependences between N-terminal phosphorylation sites, which could be classified in four clusters: Ser6 and Ser9; Ser9, Ser15, Thr18 and Ser20; Ser33 and Ser37; and Ser46. We suggest that p53 phosphorylation is regulated through a double cascade involving both the activation of secondary, effector protein kinases as well as intermolecular phosphorylation site interdependencies that check inappropriate p53 inactivation while allowing for signal amplification and the integration of signals from multiple stress pathways. JF - The Journal of biological chemistry AU - Saito, Shin'ichi AU - Yamaguchi, Hiroshi AU - Higashimoto, Yuichiro AU - Chao, Connie AU - Xu, Yang AU - Fornace, Albert J AU - Appella, Ettore AU - Anderson, Carl W AD - Laboratory of Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/09/26/ PY - 2003 DA - 2003 Sep 26 SP - 37536 EP - 37544 VL - 278 IS - 39 SN - 0021-9258, 0021-9258 KW - Tumor Suppressor Protein p53 KW - 0 KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - Phosphorylation KW - DNA Damage KW - Humans KW - Doxorubicin -- toxicity KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Protein Processing, Post-Translational KW - Tumor Suppressor Protein p53 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75700511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phosphorylation+site+interdependence+of+human+p53+post-translational+modifications+in+response+to+stress.&rft.au=Saito%2C+Shin%27ichi%3BYamaguchi%2C+Hiroshi%3BHigashimoto%2C+Yuichiro%3BChao%2C+Connie%3BXu%2C+Yang%3BFornace%2C+Albert+J%3BAppella%2C+Ettore%3BAnderson%2C+Carl+W&rft.aulast=Saito&rft.aufirst=Shin%27ichi&rft.date=2003-09-26&rft.volume=278&rft.issue=39&rft.spage=37536&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 - 2003-11-17 N1 - Date created - 2003-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dissociable contributions of the orbitofrontal and infralimbic cortex to pavlovian autoshaping and discrimination reversal learning: further evidence for the functional heterogeneity of the rodent frontal cortex. AN - 75709006; 14507977 AB - To examine possible heterogeneity of function within the ventral regions of the rodent frontal cortex, the present study compared the effects of excitotoxic lesions of the orbitofrontal cortex (OFC) and the infralimbic cortex (ILC) on pavlovian autoshaping and discrimination reversal learning. During the pavlovian autoshaping task, in which rats learn to approach a stimulus predictive of reward [conditional stimulus (CS+)], only the OFC group failed to acquire discriminated approach but was unimpaired when preoperatively trained. In the visual discrimination learning and reversal task, rats were initially required to discriminate a stimulus positively associated with reward. There was no effect of either OFC or ILC lesions on discrimination learning. When the stimulus-reward contingencies were reversed, both groups of animals committed more errors, but only the OFC-lesioned animals were unable to suppress the previously rewarded stimulus-reward association, committing more "stimulus perseverative" errors. In contrast, the ILC group showed a pattern of errors that was more attributable to "learning" than perseveration. These findings suggest two types of dissociation between the effects of OFC and ILC lesions: (1) OFC lesions impaired the learning processes implicated in pavlovian autoshaping but not instrumental simultaneous discrimination learning, whereas ILC lesions were unimpaired at autoshaping and their reversal learning deficit did not reflect perseveration, and (2) OFC lesions induced perseverative responding in reversal learning but did not disinhibit responses to pavlovian CS-. In contrast, the ILC lesion had no effect on response inhibitory control in either of these settings. The findings are discussed in the context of dissociable executive functions in ventral sectors of the rat prefrontal cortex. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Chudasama, Y AU - Robbins, Trevor W AD - Department of Experimental Psychology, University of Cambridge, Cambridge, United Kingdom CB2 3EB. yogita@ln.nimh.nih.gov Y1 - 2003/09/24/ PY - 2003 DA - 2003 Sep 24 SP - 8771 EP - 8780 VL - 23 IS - 25 KW - Neurotoxins KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Limbic System -- physiology KW - Neurotoxins -- pharmacology KW - Reaction Time -- physiology KW - Photic Stimulation -- methods KW - Rats KW - Rats, Inbred Strains KW - Retention (Psychology) -- physiology KW - Reward KW - Photic Stimulation -- instrumentation KW - Behavior, Animal -- physiology KW - Male KW - Inhibition (Psychology) KW - Discrimination Learning -- drug effects KW - Discrimination Learning -- physiology KW - Cerebral Cortex -- physiology KW - Cerebral Cortex -- drug effects KW - Conditioning, Classical -- physiology KW - Frontal Lobe -- drug effects KW - Frontal Lobe -- physiology KW - Conditioning, Classical -- drug effects KW - Reversal Learning -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75709006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dissociable+contributions+of+the+orbitofrontal+and+infralimbic+cortex+to+pavlovian+autoshaping+and+discrimination+reversal+learning%3A+further+evidence+for+the+functional+heterogeneity+of+the+rodent+frontal+cortex.&rft.au=Chudasama%2C+Y%3BRobbins%2C+Trevor+W&rft.aulast=Chudasama&rft.aufirst=Y&rft.date=2003-09-24&rft.volume=23&rft.issue=25&rft.spage=8771&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-14 N1 - Date created - 2003-09-25 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1B80; PDB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. AN - 75698688; 14504315 AB - In response to Gulf War veterans' concerns of high rates of ALS, this investigation sought to determine if Gulf War veterans have an elevated rate of ALS. A nationwide epidemiologic case ascertainment study design was used to ascertain all occurrences of ALS for the 10-year period since August 1990 among active duty military and mobilized Reserves, including National Guard, who served during the Gulf War (August 2, 1990, through July 31, 1991). The diagnosis of ALS was confirmed by medical record review. Risk was assessed by the age-adjusted, average, annual 10-year cumulative incidence rate. Among approximately 2.5 million eligible military personnel, 107 confirmed cases of ALS were identified for an overall occurrence of 0.43 per 100,000 persons per year. A significant elevated risk of ALS occurred among all deployed personnel (RR = 1.92; 95% CL = 1.29, 2.84), deployed active duty military (RR = 2.15, 95% CL = 1.38, 3.36), deployed Air Force (RR = 2.68, 95% CL = 1.24, 5.78), and deployed Army (RR = 2.04; 95% CL = 1.10, 3.77) personnel. Elevated, but nonsignificant, risks were observed for deployed Reserves and National Guard (RR = 2.50; 95% CL = 0.88, 7.07), deployed Navy (RR = 1.48, 95% CL = 0.62, 3.57), and deployed Marine Corps (RR = 1.13; 95% CL = 0.27, 4.79) personnel. Overall, the attributable risk associated with deployment was 18% (95% CL = 4.9%, 29.4%). Military personnel who were deployed to the Gulf Region during the Gulf War period experienced a greater post-war risk of ALS than those who were not deployed to the Gulf. JF - Neurology AU - Horner, R D AU - Kamins, K G AU - Feussner, J R AU - Grambow, S C AU - Hoff-Lindquist, J AU - Harati, Y AU - Mitsumoto, H AU - Pascuzzi, R AU - Spencer, P S AU - Tim, R AU - Howard, D AU - Smith, T C AU - Ryan, M A K AU - Coffman, C J AU - Kasarskis, E J AD - National Institute of Neurological Disorders and Stroke, Bethesda, MD 20852, USA. rh266m@nih.gov Y1 - 2003/09/23/ PY - 2003 DA - 2003 Sep 23 SP - 742 EP - 749 VL - 61 IS - 6 KW - Abridged Index Medicus KW - Index Medicus KW - Risk KW - Indian Ocean KW - Age of Onset KW - Humans KW - Cohort Studies KW - Adult KW - Retrospective Studies KW - Incidence KW - Middle Aged KW - Male KW - Female KW - Warfare KW - Veterans KW - Amyotrophic Lateral Sclerosis -- epidemiology KW - Persian Gulf Syndrome -- epidemiology KW - Amyotrophic Lateral Sclerosis -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75698688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Occurrence+of+amyotrophic+lateral+sclerosis+among+Gulf+War+veterans.&rft.au=Horner%2C+R+D%3BKamins%2C+K+G%3BFeussner%2C+J+R%3BGrambow%2C+S+C%3BHoff-Lindquist%2C+J%3BHarati%2C+Y%3BMitsumoto%2C+H%3BPascuzzi%2C+R%3BSpencer%2C+P+S%3BTim%2C+R%3BHoward%2C+D%3BSmith%2C+T+C%3BRyan%2C+M+A+K%3BCoffman%2C+C+J%3BKasarskis%2C+E+J&rft.aulast=Horner&rft.aufirst=R&rft.date=2003-09-23&rft.volume=61&rft.issue=6&rft.spage=742&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=1526-632X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-16 N1 - Date created - 2003-09-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Neurology. 2003 Sep 23;61(6):730-1 [14504310] Neurology. 2004 Mar 23;62(6):1027; author reply 1027-9 [15037726] Neurology. 2007 Mar 27;68(13):1083; author reply 1083 [17389322] Erratum In: Neurology. 2003 Nov 11;61(9):1320 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacterial Polymerase and Yeast Polymerase II Use Similar Mechanisms for Transcription through Nucleosomes AN - 18875318; 5723488 AB - We have previously shown that nucleosomes act as a strong barrier to yeast RNA polymerase II (Pol II) in vitro and that transcription through the nucleosome results in the loss of an H2A/H2B dimer. Here, we demonstrate that Escherichia coli RNA polymerase (RNAP), which never encounters chromatin in vivo, behaves similarly to Pol II in all aspects of transcription through the nucleosome in vitro. The nucleosome-specific pausing pattern of RNAP is comparable with that of Pol II. At physiological ionic strength or lower, the nucleosome blocks RNAP progression along the template, but this barrier can be relieved at higher ionic strength. Transcription through the nucleosome by RNAP results in the loss of an H2A/H2B dimer, and the histones that remain in the hexasome retain their original positions on the DNA. The results were similar for elongation complexes that were assembled from components (oligonucleotides and RNAP) and elongation complexes obtained by initiation from the promoter. The data suggest that eukaryotic Pol II and E. coli RNAP utilize very similar mechanisms for transcription through the nucleosome. Thus, bacterial RNAP can be used as a suitable model system to study general aspects of chromatin transcription by Pol II. Furthermore, the data argue that the general elongation properties of polymerases may determine the mechanism used for transcription through the nucleosome. JF - Journal of Biological Chemistry AU - Walter, W AU - Kireeva, M L AU - Studitsky, V M AU - Kashlev, M AD - NCI Center for Cancer Research, NCI-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702-1201, mkashlev@mail.ncifcrf.gov Y1 - 2003/09/19/ PY - 2003 DA - 2003 Sep 19 SP - 36148 EP - 36156 PB - American Society for Biochemistry and Molecular Biology, 9650 Rockville Pike Bethesda MD 20814-3996 USA, [mailto:asbmb@asbmb.faseb.org], [URL:http://www.jbc.org] VL - 278 IS - 38 SN - 0021-9258, 0021-9258 KW - PolII protein KW - RNAP protein KW - budding yeast KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biochemistry Abstracts 2: Nucleic Acids KW - K 03015:Fungi KW - J 02725:DNA KW - N 14553:Transcription initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18875318?accountid=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=Bacterial+Polymerase+and+Yeast+Polymerase+II+Use+Similar+Mechanisms+for+Transcription+through+Nucleosomes&rft.au=Walter%2C+W%3BKireeva%2C+M+L%3BStuditsky%2C+V+M%3BKashlev%2C+M&rft.aulast=Walter&rft.aufirst=W&rft.date=2003-09-19&rft.volume=278&rft.issue=38&rft.spage=36148&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M305647200 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1074/jbc.M305647200 ER - TY - JOUR T1 - Sequence context-dependent replication of DNA templates containing UV-induced lesions by human DNA polymerase iota. AN - 73548642; 12967656 AB - Humans possess four Y-family polymerases: pols eta, iota, kappa and the Rev1 protein. The pivotal role that pol eta plays in protecting us from UV-induced skin cancers is unquestioned given that mutations in the POLH gene (encoding pol eta), lead to the sunlight-sensitive and cancer-prone xeroderma pigmentosum variant phenotype. The roles that pols iota, kappa and Rev1 play in the tolerance of UV-induced DNA damage is, however, much less clear. For example, in vitro studies in which the ability of pol iota to bypass UV-induced cyclobutane pyrimidine dimers (CPDs) or 6-4 pyrimidine-pyrimidone (6-4PP) lesions has been assayed, are somewhat varied with results ranging from limited misinsertion opposite CPDs to complete lesion bypass. We have tested the hypothesis that such discrepancies might have arisen from different assay conditions and local sequence contexts surrounding each UV-photoproduct and find that pol iota can facilitate significant levels of unassisted highly error-prone bypass of a T-T CPD, particularly when the lesion is located in a 3'-A[T-T]A-5' template sequence context and the reaction buffer contains no KCl. When encountering a T-T 6-4PP dimer under the same assay conditions, pol iota efficiently and accurately inserts the correct base, A, opposite the 3'T of the 6-4PP by factors of approximately 10(2) over the incorporation of incorrect nucleotides, while incorporation opposite the 5'T is highly mutagenic. Pol kappa has been proposed to function in the bypass of UV-induced lesions by helping extend primers terminated opposite CPDs. However, we find no evidence that the combined actions of pol iota and pol kappa result in a significant increase in bypass of T-T CPDs when compared to pol iota alone. Our data suggest that under certain conditions and sequence contexts, pol iota can bypass T-T CPDs unassisted and can efficiently incorporate one or more bases opposite a T-T 6-4PP. Such biochemical activities may, therefore, be of biological significance especially in XP-V cells lacking the primary T-T CPD bypassing enzyme, pol eta. JF - DNA repair AU - Vaisman, Alexandra AU - Frank, Ekaterina G AU - Iwai, Shigenori AU - Ohashi, Eiji AU - Ohmori, Haruo AU - Hanaoka, Fumio AU - Woodgate, Roger AD - Section on DNA Replication, Repair and Mutagenesis, Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Building 6, Room 1A13, 9000 Rockville Pike, Bethesda, MD 20892-2725,USA. Y1 - 2003/09/18/ PY - 2003 DA - 2003 Sep 18 SP - 991 EP - 1006 VL - 2 IS - 9 SN - 1568-7864, 1568-7864 KW - Pyrimidine Dimers KW - 0 KW - pyrimidine-pyrimidone dimer KW - Potassium Chloride KW - 660YQ98I10 KW - DNA polymerase iota KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Base Pairing KW - Base Sequence KW - Pyrimidine Dimers -- genetics KW - Pyrimidine Dimers -- metabolism KW - Kinetics KW - Humans KW - Potassium Chloride -- pharmacology KW - Templates, Genetic KW - Substrate Specificity KW - Ultraviolet Rays KW - DNA-Directed DNA Polymerase -- pharmacology KW - DNA Damage -- radiation effects KW - DNA-Directed DNA Polymerase -- genetics KW - DNA Replication KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73548642?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+repair&rft.atitle=Sequence+context-dependent+replication+of+DNA+templates+containing+UV-induced+lesions+by+human+DNA+polymerase+iota.&rft.au=Vaisman%2C+Alexandra%3BFrank%2C+Ekaterina+G%3BIwai%2C+Shigenori%3BOhashi%2C+Eiji%3BOhmori%2C+Haruo%3BHanaoka%2C+Fumio%3BWoodgate%2C+Roger&rft.aulast=Vaisman&rft.aufirst=Alexandra&rft.date=2003-09-18&rft.volume=2&rft.issue=9&rft.spage=991&rft.isbn=&rft.btitle=&rft.title=DNA+repair&rft.issn=15687864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-28 N1 - Date created - 2003-09-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Population attributable risks of esophageal and gastric cancers. AN - 73654286; 13130116 AB - Several risk factors have been identified for esophageal adenocarcinoma, gastric cardia adenocarcinoma, esophageal squamous cell carcinoma, and noncardia gastric adenocarcinoma, but no study has comprehensively examined their contributions to the cancer burden in the general population. Herein, we estimate the population attributable risks (PARs) for various risk factors observed in a multicenter population-based case-control study. We calculated PARs by using 293 patients with esophageal adenocarcinoma, 261 with gastric cardia adenocarcinoma, 221 with esophageal squamous cell carcinoma, 368 with noncardia gastric adenocarcinoma, and 695 control subjects. We included smoking for all four tumor types and Helicobacter pylori infection for noncardia gastric adenocarcinoma as established causal risk factors as well as several other factors for which causality is under evaluation. Ever smoking, body mass index above the lowest quartile, history of gastroesophageal reflux, and low fruit and vegetable consumption accounted for 39.7% (95% confidence interval [CI] = 25.6% to 55.8%), 41.1% (95% CI = 23.8% to 60.9%), 29.7% (95% CI = 19.5% to 42.3%), and 15.3% (95% CI = 5.8% to 34.6%) of esophageal adenocarcinomas, respectively, with a combined PAR of 78.7% (95% CI = 66.5% to 87.3%). Ever smoking and body mass index above the lowest quartile were responsible for 45.2% (95% CI = 31.3% to 59.9%) and 19.2% (95% CI = 4.9% to 52.0%) of gastric cardia adenocarcinomas, respectively, with a combined PAR of 56.2% (95% CI = 38.1% to 72.8%). Ever smoking, alcohol consumption, and low fruit and vegetable consumption accounted for 56.9% (95% CI = 36.6% to 75.1%), 72.4% (95% CI = 53.3% to 85.8%), and 28.7% (95% CI = 11.1% to 56.5%) of esophageal squamous cell carcinomas, respectively, with a combined PAR of 89.4% (95% CI = 79.1% to 95.0%). Ever smoking, history of gastric ulcers, nitrite intake above the lowest quartile, and H. pylori infection were responsible for 18.3% (95% CI = 6.5% to 41.8%), 9.7% (95% CI = 5.4% to 16.8%), 40.7% (95% CI = 23.4% to 60.7%), and 10.4% (95% CI = 0.3% to 79.6%) of noncardia gastric adenocarcinomas, respectively, with a combined PAR of 59.0% (95% CI = 16.2% to 91.4%). In this population, a few known risk factors account for a majority of esophageal and gastric cancers. These results suggest that the incidence of these cancers may be decreased by reducing the prevalence of smoking, gastroesophageal reflux, and being overweight and by increasing the consumption of fruits and vegetables. JF - Journal of the National Cancer Institute AU - Engel, Lawrence S AU - Chow, Wong-Ho AU - Vaughan, Thomas L AU - Gammon, Marilie D AU - Risch, Harvey A AU - Stanford, Janet L AU - Schoenberg, Janet B AU - Mayne, Susan T AU - Dubrow, Robert AU - Rotterdam, Heidrun AU - West, A Brian AU - Blaser, Martin AU - Blot, William J AU - Gail, Mitchell H AU - Fraumeni, Joseph F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. engell@mskcc.org Y1 - 2003/09/17/ PY - 2003 DA - 2003 Sep 17 SP - 1404 EP - 1413 VL - 95 IS - 18 KW - Nitrites KW - 0 KW - Index Medicus KW - United States KW - Vegetables KW - Carcinoma, Squamous Cell -- etiology KW - Humans KW - Alcohol Drinking -- adverse effects KW - Aged KW - Risk Assessment KW - Adult KW - Enzyme-Linked Immunosorbent Assay KW - Fruit KW - Male KW - Stomach Ulcer -- complications KW - Smoking -- adverse effects KW - Body Mass Index KW - Feeding Behavior KW - Obesity -- complications KW - Gastroesophageal Reflux -- complications KW - Adenocarcinoma -- etiology KW - Nitrites -- adverse effects KW - Risk Factors KW - Confounding Factors (Epidemiology) KW - Case-Control Studies KW - Cardia KW - Middle Aged KW - Female KW - Life Style KW - Stomach Neoplasms -- epidemiology KW - Stomach Neoplasms -- etiology KW - Esophageal Neoplasms -- etiology KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73654286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Population+attributable+risks+of+esophageal+and+gastric+cancers.&rft.au=Engel%2C+Lawrence+S%3BChow%2C+Wong-Ho%3BVaughan%2C+Thomas+L%3BGammon%2C+Marilie+D%3BRisch%2C+Harvey+A%3BStanford%2C+Janet+L%3BSchoenberg%2C+Janet+B%3BMayne%2C+Susan+T%3BDubrow%2C+Robert%3BRotterdam%2C+Heidrun%3BWest%2C+A+Brian%3BBlaser%2C+Martin%3BBlot%2C+William+J%3BGail%2C+Mitchell+H%3BFraumeni%2C+Joseph+F&rft.aulast=Engel&rft.aufirst=Lawrence&rft.date=2003-09-17&rft.volume=95&rft.issue=18&rft.spage=1404&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=1460-2105&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-23 N1 - Date created - 2003-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quality of Life in elderly patients with cancer. AN - 71616793; 14525617 AB - The incidence of most types of cancers is age-dependent and the progressive ageing is rapidly increasing the number of elderly people who need treatment for cancer. Elderly patients present peculiar characteristics that make the choice of the correct treatment more difficult and these patients are often undertreated. Moreover, elderly patients are largely underrepresented in cancer treatment trials, and this makes the experimental evidence on this topic even weaker. Health-related Quality of Life (QOL) has been considered as one of the hard end-points for clinical cancer research, and treatment of elderly cancer patients represents a typical situation where its assessment can be particularly useful, because the expected toxicity of treatment could be relevant in the discussion of the treatment choice. However, QOL assessment in the elderly is complicated by several unresolved methodological problems (higher frequency of illiteracy, worse compliance with the questionnaires, concomitant diseases, use of instruments not validated in the aged population). Conduct of clinical trials dedicated to elderly patients is now encouraged but there are few published studies. Advanced non-small-cell lung cancer is one of the fields with the largest amount of research on QOL in elderly patients. The ELVIS study demonstrated the efficacy of single-agent chemotherapy, both in terms of QOL and of survival. The MILES study, in which combination chemotherapy was not superior than single agents, showed that baseline QOL is a strong prognostic indicator in these patients. QOL of patients with breast cancer has been another important field in clinical research over the last decades, and interest on this topic in elderly patients is growing, from loco-regional to palliative treatment. In conclusion, some steps have been done in clinical cancer research dedicated to elderly patients, and the role of QOL assessment in this setting is important. However, many methodological problems must be resolved, in order to obtain reliable and useful results. A QOL assessment could also be useful for elderly patients in clinical practice, where it could improve patient-clinician communication: a wider application of properly selected instruments should be recommended. JF - Health and quality of life outcomes AU - Di Maio, Massimo AU - Perrone, Francesco AD - Clinical Trials Unit, National Cancer Institute, 80131 Naples, Italy. dimaiomax@libero.it Y1 - 2003/09/17/ PY - 2003 DA - 2003 Sep 17 SP - 44 VL - 1 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Vinblastine KW - 5V9KLZ54CY KW - vinorelbine KW - Q6C979R91Y KW - Index Medicus KW - Vinblastine -- therapeutic use KW - Vinblastine -- analogs & derivatives KW - Reproducibility of Results KW - Lung Neoplasms -- psychology KW - Humans KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Lung Neoplasms -- drug therapy KW - Surveys and Questionnaires KW - Clinical Trials as Topic -- standards KW - Breast Neoplasms KW - Aged KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Carcinoma, Non-Small-Cell Lung -- psychology KW - Geriatric Assessment -- methods KW - Quality of Life KW - Neoplasms -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71616793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+and+quality+of+life+outcomes&rft.atitle=Quality+of+Life+in+elderly+patients+with+cancer.&rft.au=Di+Maio%2C+Massimo%3BPerrone%2C+Francesco&rft.aulast=Di+Maio&rft.aufirst=Massimo&rft.date=2003-09-17&rft.volume=1&rft.issue=&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=Health+and+quality+of+life+outcomes&rft.issn=1477-7525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2009-06-30 N1 - Date created - 2008-01-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1999 Dec 30;341(27):2061-7 [10615079] JAMA. 1999 Feb 10;281(6):545-51 [10022111] Qual Life Res. 2000;9(4):369-75 [11131929] Am J Clin Oncol. 2001 Dec;24(6):591-6 [11801761] Ann Oncol. 2001;12 Suppl 3:S21-5 [11804379] Ann Oncol. 2001;12 Suppl 3:S49-52 [11804385] J Clin Oncol. 2002 Feb 1;20(3):770-5 [11821460] J Natl Cancer Inst. 2002 Feb 6;94(3):173-81 [11830607] Lancet Oncol. 2002 May;3(5):289-97 [12067806] J Natl Cancer Inst. 2002 Jul 3;94(13):1029-30; author reply 1030-1 [12096088] Cancer. 2002 May 15;94(10):2766-92 [12173348] Crit Rev Oncol Hematol. 2002 Sep;43(3):219-26 [12270778] JAMA. 2002 Dec 18;288(23):3027-34 [12479768] J Natl Cancer Inst. 2003 Feb 19;95(4):263-81 [12591983] J Natl Cancer Inst. 2003 Mar 5;95(5):362-72 [12618501] J Clin Oncol. 2003 Apr 1;21(7):1383-9 [12663731] J Oncol Manag. 2003 Mar-Apr;12(2):13-7 [12699111] Eur J Cancer. 2003 May;39(7):870-80 [12706355] Eur J Cancer. 2003 May;39(7):945-51 [12706363] Lancet. 1990 Apr 28;335(8696):1020-2 [1970072] Cancer. 1991 Jun 15;67(12):3131-5 [1710541] J Clin Oncol. 1993 Mar;11(3):570-9 [8445433] J Clin Epidemiol. 1993 Dec;46(12):1433-44 [8263570] J Clin Oncol. 1996 Feb;14(2):671-9 [8636786] BMJ. 1998 Sep 19;317(7161):771-5 [9740561] J Natl Cancer Inst. 1999 Jan 6;91(1):66-72 [9890172] J Clin Oncol. 2000 Apr;18(7):1412-22 [10735888] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for an enantioselective pumiliotoxin 7-hydroxylase in dendrobatid poison frogs of the genus Dendrobates. AN - 73658456; 12960405 AB - Dendrobatid poison frogs readily accumulate alkaloids from diet into skin, where such compounds serve as a chemical defense against predators. Arthropods seem to be the source of decahydroquinolines (DHQs), several izidines, coccinellines, spiropyrrolizidines, pumiliotoxins (PTXs), and allopumiliotoxins (aPTXs). A DHQ iso-223F, and PTX (+)-251D were fed to poison frogs of the dendrobatid genera Dendrobates, Epipedobates, and Phyllobates. The two alkaloids were accumulated in skin unchanged except for the three species of Dendrobates, where approximately 80% of accumulated PTX (+)-251D was stereoselectively hydroxylated to aPTX (+)-267A. The unnatural enantiomer PTX (-)-251D was accumulated efficiently when fed to Dendrobates auratus, but was not hydroxylated. The enantiomers of PTX 251D and their desmethyl analogs were synthesized from N-Boc-protected (-)- and (+)-proline methyl esters. Both PTX (+)-251D and aPTX (+)-267A proved to be potent convulsants in mice, with (+)-267A being approximately 5-fold more toxic than (+)-251D. Both alkaloids were hyperalgesic at the site of injection. The unnatural PTX (-)-251D caused no overt effect in mice. Thus, the evolutionary development of a pumiliotoxin 7-hydroxylase would have provided frogs of the genus Dendrobates with a means of enhancing the antipredator potency of ingested PTXs. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Daly, John W AU - Garraffo, H Martin AU - Spande, Thomas F AU - Clark, Valerie C AU - Ma, Jingyuan AU - Ziffer, Herman AU - Cover, John F AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-0820, USA. jdaly@nih.gov Y1 - 2003/09/16/ PY - 2003 DA - 2003 Sep 16 SP - 11092 EP - 11097 VL - 100 IS - 19 SN - 0027-8424, 0027-8424 KW - Mixed Function Oxygenases KW - EC 1.- KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Anura KW - Hydroxylation KW - Mixed Function Oxygenases -- chemistry KW - Mixed Function Oxygenases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73658456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+for+an+enantioselective+pumiliotoxin+7-hydroxylase+in+dendrobatid+poison+frogs+of+the+genus+Dendrobates.&rft.au=Daly%2C+John+W%3BGarraffo%2C+H+Martin%3BSpande%2C+Thomas+F%3BClark%2C+Valerie+C%3BMa%2C+Jingyuan%3BZiffer%2C+Herman%3BCover%2C+John+F&rft.aulast=Daly&rft.aufirst=John&rft.date=2003-09-16&rft.volume=100&rft.issue=19&rft.spage=11092&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 - 2003-10-29 N1 - Date created - 2003-09-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Med Chem. 1985 Apr;28(4):482-6 [3981541] Science. 1980 Jun 20;208(4450):1383-5 [6246586] J Med Chem. 1988 Feb;31(2):477-80 [2448459] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1272-6 [2448797] Biochem Pharmacol. 1990 Jul 15;40(2):315-26 [2165404] J Nat Prod. 1990 Mar-Apr;53(2):407-21 [2380714] Toxicon. 1992 Aug;30(8):887-98 [1523680] Mol Pharmacol. 1992 Dec;42(6):1104-8 [1336116] J Nat Prod. 1993 Mar;56(3):357-73 [8482947] J Nat Prod. 1993 Jul;56(7):1016-38 [8377013] Toxicon. 1994 Jun;32(6):657-63 [7940573] Toxicon. 1997 Jul;35(7):1131-5 [9248011] J Nat Prod. 1998 Jan;61(1):162-72 [9461669] Mol Phylogenet Evol. 2000 Apr;15(1):34-40 [10764533] J Nat Prod. 2001 Apr;64(4):421-7 [11325220] J Nat Prod. 2002 Apr;65(4):439-47 [11975476] Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):13996-4001 [12381780] Toxicon. 1978;16(2):163-88 [635931] Toxicon. 1987;25(10):1023-95 [3321567] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacterial pathogens modulate an apoptosis differentiation program in human neutrophils AN - 18872831; 5717305 AB - Human polymorphonuclear leukocytes (PMNs or neutrophils) are essential to the innate immune response against bacterial pathogens. Recent evidence suggests that PMN apoptosis facilitates resolution of inflammation during bacterial infection. Although progress has been made toward understanding apoptosis in neutrophils, very little is known about transcriptional regulation of this process during bacterial infection. To gain insight into the molecular processes that facilitate resolution of infection, we measured global changes in PMN gene expression during phagocytosis of a diverse group of bacterial pathogens. Genes encoding key effectors of apoptosis were up-regulated, and receptors critical to innate immune function were down-regulated during apoptosis induced by phagocytosis of Burkholderia cepacia, Borrelia hermsii, Listeria monocytogenes, Staphylococcus aureus, and Streptococcus pyogenes. Importantly, we identified genes that comprise a common apoptosis differentiation program in human PMNs after phagocytosis of pathogenic bacteria. Unexpectedly, phagocytosis of Str. pyogenes induced changes in neutrophil gene expression not observed with other pathogens tested, including down- regulation of 21 genes involved in responses to IFN. Compared with other bacteria, PMN apoptosis was significantly accelerated by Str. pyogenes and was followed by necrosis. Thus, we hypothesize that there are two fundamental outcomes for the interaction of bacterial pathogens with neutrophils: (i) phagocytosis of bacteria induces an apoptosis differentiation program in human PMNs that contributes to resolution of bacterial infection, or (ii) phagocytosis of microorganisms such as Str. pyogenes alters the apoptosis differentiation program in neutrophils, resulting in pathogen survival and disease. JF - Proceedings of the National Academy of Sciences, USA AU - Kobayashi, S D AU - Braughton, K R AU - Whitney, A R AU - Voyich, J M AU - Schwan, T G AU - Musser, J M AU - DeLeo AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, fdeleo@niaid.nih.gov Y1 - 2003/09/16/ PY - 2003 DA - 2003 Sep 16 SP - 10948 EP - 10953 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 19 SN - 0027-8424, 0027-8424 KW - man KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms KW - N 14550:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18872831?accountid=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=Bacterial+pathogens+modulate+an+apoptosis+differentiation+program+in+human+neutrophils&rft.au=Kobayashi%2C+S+D%3BBraughton%2C+K+R%3BWhitney%2C+A+R%3BVoyich%2C+J+M%3BSchwan%2C+T+G%3BMusser%2C+J+M%3BDeLeo&rft.aulast=Kobayashi&rft.aufirst=S&rft.date=2003-09-16&rft.volume=100&rft.issue=19&rft.spage=10948&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.1833375100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.1833375100 ER - TY - JOUR T1 - Formation of tamoxifen-DNA adducts in multiple organs of adult female cynomolgus monkeys dosed with tamoxifen for 30 days. AN - 75745763; 14522927 AB - The use of the antiestrogen tamoxifen (TAM) is associated with an increase in endometrial cancer. TAM-induced endometrial carcinogenesis may proceed through a genotoxin-mediated pathway, although the detection of endometrial TAM-DNA adducts in exposed women is still controversial. In this study, a monkey model has been used to investigate the question of TAM-DNA adduct formation in primates. Two methods have been used to determine TAM-DNA adducts: a TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), using an antiserum that has specificity for (E)-alpha-(deoxyguanosin-N(2)-yl)-tamoxifen (dG-TAM) and (E)-alpha-(deoxyguanosin-N(2)-yl)-N-desmethyltamoxifen (dG-desmethyl-TAM) and electrospray ionization tandem mass spectrometry (ES-MS/MS) coupled with on-line sample preparation and high-performance liquid chromatography (HPLC). Mature (19 year old) cynomolgus monkeys were given either vehicle control (n = 1) or TAM (n = 3) twice daily for a total dose of 2 mg of TAM/kg body weight (bw)/day for 30 days by naso-gastric intubation. Tissues were harvested, and DNA was isolated from uterus, ovary, liver, brain cortex, and kidney. By TAM-DNA CIA, values for uterine TAM-DNA adducts in two monkeys were 0.9 and 1.7 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts in the same animals were 0.4 and 0.5 adducts/10(8) nucleotides. Liver, brain cortex, and kidney DNA samples from the three exposed monkeys had TAM-DNA levels of 2.1-4.2 adducts/10(8) nucleotides, 0.4-5.0 adducts/10(8) nucleotides, and 0.7-2.1 adducts/10(8) nucleotides, respectively. By HPLC-ES-MS/MS, the levels of TAM-DNA adducts detected in all tissues were comparable with those observed by TAM-DNA CIA. Thus, values for uterine TAM-DNA adducts ranged from 0.5 to 1.4 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts, measurable in two monkeys, were 0.2 and 0.3 adducts/10(8) nucleotides. Liver DNA contained the highest TAM-DNA adduct levels (7.0-11.1 adducts/10(8) nucleotides), whereas brain cortex DNA contained lower adduct levels (0.6-4.8 adducts/10(8) nucleotides) and the lowest levels were measured in the kidney (0.2-0.4 adducts/10(8) nucleotides). This study indicates that cynomolgus monkeys are capable of metabolizing TAM to genotoxic intermediates that form TAM-DNA adducts in multiple tissues. JF - Cancer research AU - Schild, Laura J AU - Divi, Rao L AU - Beland, Frederick A AU - Churchwell, Mona I AU - Doerge, Daniel R AU - Gamboa da Costa, Gonçalo AU - Marques, M Matilde AU - Poirier, Miriam C AD - Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 5999 EP - 6003 VL - 63 IS - 18 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents, Hormonal KW - 0 KW - DNA Adducts KW - Estrogen Receptor Modulators KW - Tamoxifen KW - 094ZI81Y45 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Uterus -- chemistry KW - Spectrometry, Mass, Electrospray Ionization KW - Animals KW - Ovary -- chemistry KW - Kidney -- metabolism KW - Macaca fascicularis KW - Estrogen Receptor Modulators -- toxicity KW - Cerebral Cortex -- metabolism KW - Liver -- metabolism KW - Kidney -- chemistry KW - Liver -- chemistry KW - Chromatography, High Pressure Liquid KW - Uterus -- metabolism KW - Ovary -- metabolism KW - Cerebral Cortex -- chemistry KW - Luminescent Measurements KW - Estrogen Receptor Modulators -- metabolism KW - Female KW - Tamoxifen -- toxicity KW - DNA Adducts -- biosynthesis KW - DNA Adducts -- analysis KW - DNA -- metabolism KW - Tamoxifen -- metabolism KW - DNA -- drug effects KW - Antineoplastic Agents, Hormonal -- toxicity KW - Antineoplastic Agents, Hormonal -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75745763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Formation+of+tamoxifen-DNA+adducts+in+multiple+organs+of+adult+female+cynomolgus+monkeys+dosed+with+tamoxifen+for+30+days.&rft.au=Schild%2C+Laura+J%3BDivi%2C+Rao+L%3BBeland%2C+Frederick+A%3BChurchwell%2C+Mona+I%3BDoerge%2C+Daniel+R%3BGamboa+da+Costa%2C+Gon%C3%A7alo%3BMarques%2C+M+Matilde%3BPoirier%2C+Miriam+C&rft.aulast=Schild&rft.aufirst=Laura&rft.date=2003-09-15&rft.volume=63&rft.issue=18&rft.spage=5999&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 - 2003-12-04 N1 - Date created - 2003-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deregulation of the cyclin D1/Cdk4 retinoblastoma pathway in rat mammary gland carcinomas induced by the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. AN - 75739778; 14522882 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a suspected human breast carcinogen found in cooked meat that induces mammary gland cancer in rats. By real time PCR analysis, PhIP-induced rat mammary gland carcinomas showed statistically higher expression of the G(1)-S cyclin D1 (5-fold) and its kinase partner cyclin-dependent kinase (Cdk)-4 (37-fold) in comparison with normal mammary gland, whereas cyclin D2, cyclin D3, and Cdk6 were not statistically changed. Amplification of cyclin D1 was observed by real time PCR in 24% of carcinomas (15 of 63). Only 1 of 47 carcinomas showed Cdk4 amplification. By Western blotting, the level of phospho-Rb was >2-fold higher in carcinomas than in normal mammary gland. By immunohistochemical analysis, cyclin D1, Cdk4, and phospho-Rb nuclear protein expression was 5.7-, 3.9-, and 2.3-fold higher, respectively, in carcinomas than in normal mammary gland, whereas the expression of cyclin D2, cyclin D3, and Cdk6 was similar. Among carcinomas, Cdk4 and phospho-Rb levels were positively correlated with cell proliferation. Previous studies by this laboratory indicated that these carcinomas harbor a high frequency of H-ras mutations. The H-ras pathway is linked to the cell cycle via cyclin D1. The results from the current study implicate cyclin D1/Cdk4, phospho-Rb as a central pathway in PhIP-induced rat mammary gland carcinogenesis. JF - Cancer research AU - Qiu, Cunping AU - Shan, Liang AU - Yu, Minshu AU - Snyderwine, Elizabeth G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Health of Institutes, Bethesda, Maryland 20892-4262, USA. Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 5674 EP - 5678 VL - 63 IS - 18 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - Imidazoles KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Retinoblastoma Protein KW - Cyclin D1 KW - 136601-57-5 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Cdk4 protein, rat KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinase 4 KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Animals KW - Cell Cycle -- physiology KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Rats KW - Signal Transduction -- physiology KW - Blotting, Western KW - Rats, Sprague-Dawley KW - Signal Transduction -- drug effects KW - Gene Amplification -- drug effects KW - Immunohistochemistry KW - Cell Cycle -- drug effects KW - Female KW - Cyclin-Dependent Kinases -- metabolism KW - Imidazoles -- toxicity KW - Cyclin-Dependent Kinases -- physiology KW - Carcinogens -- toxicity KW - Retinoblastoma Protein -- physiology KW - Mammary Neoplasms, Experimental -- genetics KW - Cyclin D1 -- genetics KW - Mammary Neoplasms, Experimental -- metabolism KW - Cyclin D1 -- physiology KW - Mammary Neoplasms, Experimental -- pathology KW - Mammary Neoplasms, Experimental -- chemically induced KW - Cyclin D1 -- metabolism KW - Retinoblastoma Protein -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75739778?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Deregulation+of+the+cyclin+D1%2FCdk4+retinoblastoma+pathway+in+rat+mammary+gland+carcinomas+induced+by+the+food-derived+carcinogen+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine.&rft.au=Qiu%2C+Cunping%3BShan%2C+Liang%3BYu%2C+Minshu%3BSnyderwine%2C+Elizabeth+G&rft.aulast=Qiu&rft.aufirst=Cunping&rft.date=2003-09-15&rft.volume=63&rft.issue=18&rft.spage=5674&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 - 2003-12-04 N1 - Date created - 2003-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lymphodepleting effects and safety of pentostatin for nonmyeloablative allogeneic stem-cell transplantation. AN - 75707106; 14501873 AB - Nonmyeloablative allogeneic stem-cell transplantation (alloNST) is the focus of investigations searching for less-toxic transplantation regimens. We report studies on the kinetics of lymphodepletion and safety of pentostatin (PT) conditioning in alloNST. Patients with hematologic malignancy received mobilized blood from human leukocyte antigen-matched related (n=4) or unrelated (n=8) donors. PT 4 mg/m2 was administered on days -21, -20, and -19 and 200 cGy of total-body irradiation was administered on day -1, followed by cyclosporine A and mycophenolate mofetil. Mononuclear cell adenosine deaminase after PT was inhibited 84%. The absolute CD3+ cells decreased significantly by day -7 (49%) and CD19+ cells declined 92% by day -1. CD4+ cells were depressed more than CD8+ cells. Neutrophils and monocytes were minimally affected by PT. Median posttransplant peripheral blood chimerism on day 70 showed 95% donor leukocytes and 82.5% donor CD3 lymphocytes. PT demonstrated lymphodepleting effects and promising safety, supporting alloNST as early as 7 days after initiation of PT. JF - Transplantation AU - Pavletic, Steven Z AU - Bociek, R Gregory AU - Foran, James M AU - Rubocki, Ronald J AU - Kuszynski, Charles A AU - Wisecarver, James L AU - Hatcher, Lori AU - Lucas, David M AU - Byrd, John C AU - Grever, Michael R AU - Joshi, Shantaram S AU - Hardiman, Penny AU - Smith, Lynette M AU - McGuire, Timothy R AU - Bierman, Philip J AU - Vose, Julie M AU - Armitage, James O AU - Talmadge, James E AD - Department of Internal Medicine, Section of Oncology/Hematology, University of Nebraska Medical Center, Omaha, NE, USA. pavletis@mail.nih.gov Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 877 EP - 881 VL - 76 IS - 5 SN - 0041-1337, 0041-1337 KW - Immunosuppressive Agents KW - 0 KW - Pentostatin KW - 395575MZO7 KW - Index Medicus KW - Neutrophils -- drug effects KW - Humans KW - Adult KW - Monocytes -- drug effects KW - Aged KW - Pilot Projects KW - Middle Aged KW - Transplantation, Homologous KW - Male KW - Female KW - CD8-Positive T-Lymphocytes -- drug effects KW - Pentostatin -- administration & dosage KW - CD4-Positive T-Lymphocytes -- drug effects KW - Stem Cell Transplantation KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75707106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transplantation&rft.atitle=Lymphodepleting+effects+and+safety+of+pentostatin+for+nonmyeloablative+allogeneic+stem-cell+transplantation.&rft.au=Pavletic%2C+Steven+Z%3BBociek%2C+R+Gregory%3BForan%2C+James+M%3BRubocki%2C+Ronald+J%3BKuszynski%2C+Charles+A%3BWisecarver%2C+James+L%3BHatcher%2C+Lori%3BLucas%2C+David+M%3BByrd%2C+John+C%3BGrever%2C+Michael+R%3BJoshi%2C+Shantaram+S%3BHardiman%2C+Penny%3BSmith%2C+Lynette+M%3BMcGuire%2C+Timothy+R%3BBierman%2C+Philip+J%3BVose%2C+Julie+M%3BArmitage%2C+James+O%3BTalmadge%2C+James+E&rft.aulast=Pavletic&rft.aufirst=Steven&rft.date=2003-09-15&rft.volume=76&rft.issue=5&rft.spage=877&rft.isbn=&rft.btitle=&rft.title=Transplantation&rft.issn=00411337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-17 N1 - Date created - 2003-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased hepatitis C virus load among injection drug users infected with human immunodeficiency virus and human T lymphotropic virus type II. AN - 73654320; 12964121 AB - Coinfection of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) and/or human T-lymphotropic virus type II (HTLV-II) is common among drug users. We compared HCV RNA detection and load in a cohort of 6570 injection drug users from 9 US cities during 1987-1991. Of 385 subjects selected from 16 strata by sex, race (black or nonblack), and HIV/HTLV-II group (HIV positive [HIV(+)]/HTLV-II(+), HIV(+)/HTLV-II negative [HTLV-II(-)], HIV(-)/HTLV-II(+), and HIV(-)/HTLV-II(-)), 376 had HCV antibodies, of whom 305 had detectable HCV load. HCV RNA detection was unrelated to sex, race, and virus groups, but differed by study site. The mean HCV load was 5.4 log(10) IU/mL and was 0.24 log(10) higher in men than in women. Virus load increment with HIV or HTLV-II infection was higher among white subjects than among other subjects. Compared with HIV(-)/HTLV-II(-) subjects, virus load was 0.50, 0.22, and 0.56 log(10) higher in HIV(+)/HTLV-II(-), HIV(-)/HTLV-II(+), and HIV(+)/HTLV-II(+) subjects, respectively. HTLV-II infection significantly increased HCV load in white subjects but not in other racial groups. JF - The Journal of infectious diseases AU - Hisada, Michie AU - Chatterjee, Nilanjan AU - Zhang, Mingdong AU - Battjes, Robert J AU - Goedert, James J AD - Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20851, USA. hisadam@exchange.nih.gov Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 891 EP - 897 VL - 188 IS - 6 SN - 0022-1899, 0022-1899 KW - Hepatitis C Antibodies KW - 0 KW - RNA, Viral KW - Abridged Index Medicus KW - Index Medicus KW - Hepatitis C -- virology KW - Hepatitis C -- complications KW - Hepatitis C Antibodies -- blood KW - Human T-lymphotropic virus 2 KW - Humans KW - Aged KW - HIV-1 KW - Adult KW - Cohort Studies KW - Middle Aged KW - Female KW - Male KW - RNA, Viral -- blood KW - Viral Load KW - Hepacivirus -- physiology KW - HIV Infections -- complications KW - HTLV-II Infections -- complications KW - Substance Abuse, Intravenous -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73654320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Increased+hepatitis+C+virus+load+among+injection+drug+users+infected+with+human+immunodeficiency+virus+and+human+T+lymphotropic+virus+type+II.&rft.au=Hisada%2C+Michie%3BChatterjee%2C+Nilanjan%3BZhang%2C+Mingdong%3BBattjes%2C+Robert+J%3BGoedert%2C+James+J&rft.aulast=Hisada&rft.aufirst=Michie&rft.date=2003-09-15&rft.volume=188&rft.issue=6&rft.spage=891&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-15 N1 - Date created - 2003-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Supportive care in patients with advanced non-small-cell lung cancer. AN - 73639017; 12966418 AB - The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults. JF - British journal of cancer AU - Di Maio, M AU - Perrone, F AU - Gallo, C AU - Iaffaioli, R V AU - Manzione, L AU - Piantedosi, F V AU - Cigolari, S AU - Illiano, A AU - Barbera, S AU - Robbiati, S F AU - Piazza, E AU - Ianniello, G P AU - Frontini, L AU - Veltri, E AU - Castiglione, F AU - Rosetti, F AU - De Maio, E AU - Maione, P AU - Gridelli, C AU - Rossi, Antonio AU - Barletta, Emiddio AU - Barzelloni, Maria Luisa AU - Signoriello, Giuseppe AU - Bilancia, Domenico AU - Dinota, Angela AU - Rosati, Gerardo AU - Germano, Domenico AU - Lamberti, Alfredo AU - Pontillo, Vittorio AU - Brancacio, Luigi AU - Crispino, Carlo AU - Esposito, Maria AU - Battiloro, Ciro AU - Tufano, Giovanni AU - Cioffi, Angela AU - Guardasole, Vincenzo AU - Angelini, Valentina AU - Guidetti, Giovanna AU - Barbera, Santi AU - Renda, Francesco AU - Romano, Francesco AU - Volpintesta, Antonio AU - Robbiati, Sergio Federico AU - Sannicolò, Mirella AU - Filipazzi, Virginio AU - Esani, Gabriella AU - Gambaro, Anna AU - Ferrario, Sabrina AU - Tinessa, Vincenza AU - Caprio, Maria Grazia AU - Zonato, Sabrina AU - Cabiddu, Mary AU - Raina, Alberto AU - Veltri, Enzo AU - D'Aprile, Modesto AU - Pistillucci, Giorgio AU - Porcile, Gianfranco AU - Ostellino, Oliviero AU - Vinante, Orazio AU - Azzarello, Giuseppe AU - Gebbia, Vittorio AU - Borsellino, Nicola AU - Testa, Antonio AU - Gasparini, Giampietro AU - Morabito, Alessandra AU - Gattuso, Domenico AU - Romito, Sante AU - Carrozza, Francesco AU - Fava, Sergio AU - Calcagno, Anna AU - Grimi, Emanuela AU - Bertetto, Oscar AU - Ciuffreda, Libero AU - Parello, Giuseppe AU - Maiorino, Luigi AU - Santoro, Antonio AU - Santoro, Massimiliano AU - Failla, Giuseppe AU - Aiello, Rosa Anna AU - Bearz, Alessandra AU - Sorio, Roberto AU - Scalone, Simona AU - Clerici, Maurizia AU - Bollina, Roberto AU - Belloni, Paolo AU - Sacco, Cosimo AU - Sibau, Angela AU - Adamo, Vincenzo AU - Altavilla, Giuseppe AU - Scimone, Antonino AU - Spatafora, Mario AU - Bellia, Vincenzo AU - Hopps, Maria Raffealla AU - Monfardini, Silvio AU - Favaretto, Adolfo AU - Stefani, Micaela AU - Corradini, Giuliana Mara AU - Pavia, Gianfranco AU - Scagliotti, Giorgio AU - Novello, Silvia AU - Selvaggi, Giovanni AU - Tonato, Maurizio AU - Darwish, Samir AU - Michetti, Giovanni AU - Belometti, Maria Ori AU - Labianca, Roberto AU - Quadri, Antonello AU - De Marinis, Filippo AU - Migliorino, Maria Rita AU - Martelli, Olga AU - Colucci, Giuseppe AU - Galetta, Dominico AU - Giotta, Francesco AU - Isa, Luciano AU - Candido, Paola AU - Rossi, Nestore AU - Calandriello, Antonio AU - Ferraù, Francesco AU - Malaponte, Emilia AU - Barni, Sandro AU - Cazzaniga, Marina AU - Gebbia, Nicola AU - Valerio, Maria Rosaria AU - Belli, Mario AU - Colantuoni, Giuseppe AU - Capuano, Matteo Antonio AU - Angiolillo, Michele AU - Sollitto, Francesco AU - Ardizzoia, Antonio AU - Luporini, Gino AU - Locatelli, Maria Cristina AU - Pari, Franca AU - Aitini, Enrico AU - Pedicini, Tonino AU - Febbraro, Antonio AU - Zollo, Cesira AU - Di Costanzo, Francesco AU - Bartolucci, Roberta AU - Gasperoni, Silvia AU - Gaion, Fernando AU - Palazzolo, Giovanni AU - Galligioni, Enzo AU - Caffo, Orazio AU - Cortesi, Enrico AU - D'Auria, Giuliana AU - Curcio, Carlo AU - Vasta, Matteo AU - Bumma, Cesare AU - Celano, Alfredo AU - Bretti, Sergio AU - Nettis, Giuseppe AU - Anselmo, Annamaria AU - Mattioli, Rodolfo AU - Nisticò, Cecilia AU - Aschelter, Annamaria AU - Foa, Paola AD - National Cancer Institute: Clinical Trials Unit, Naples Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 1013 EP - 1021 VL - 89 IS - 6 SN - 0007-0920, 0007-0920 KW - Antiemetics KW - 0 KW - Deoxycytidine KW - 0W860991D6 KW - Vinblastine KW - 5V9KLZ54CY KW - gemcitabine KW - B76N6SBZ8R KW - Cisplatin KW - Q20Q21Q62J KW - vinorelbine KW - Q6C979R91Y KW - Index Medicus KW - Antiemetics -- therapeutic use KW - Randomized Controlled Trials as Topic KW - Survival Rate KW - Aged, 80 and over KW - Humans KW - Aging KW - Adult KW - Quality of Life KW - Palliative Care KW - Aged KW - Middle Aged KW - Male KW - Female KW - Cisplatin -- administration & dosage KW - Vinblastine -- analogs & derivatives KW - Lung Neoplasms -- secondary KW - Deoxycytidine -- analogs & derivatives KW - Lung Neoplasms -- drug therapy KW - Vinblastine -- administration & dosage KW - Deoxycytidine -- administration & dosage KW - Carcinoma, Non-Small-Cell Lung -- secondary KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73639017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Supportive+care+in+patients+with+advanced+non-small-cell+lung+cancer.&rft.au=Di+Maio%2C+M%3BPerrone%2C+F%3BGallo%2C+C%3BIaffaioli%2C+R+V%3BManzione%2C+L%3BPiantedosi%2C+F+V%3BCigolari%2C+S%3BIlliano%2C+A%3BBarbera%2C+S%3BRobbiati%2C+S+F%3BPiazza%2C+E%3BIanniello%2C+G+P%3BFrontini%2C+L%3BVeltri%2C+E%3BCastiglione%2C+F%3BRosetti%2C+F%3BDe+Maio%2C+E%3BMaione%2C+P%3BGridelli%2C+C%3BRossi%2C+Antonio%3BBarletta%2C+Emiddio%3BBarzelloni%2C+Maria+Luisa%3BSignoriello%2C+Giuseppe%3BBilancia%2C+Domenico%3BDinota%2C+Angela%3BRosati%2C+Gerardo%3BGermano%2C+Domenico%3BLamberti%2C+Alfredo%3BPontillo%2C+Vittorio%3BBrancacio%2C+Luigi%3BCrispino%2C+Carlo%3BEsposito%2C+Maria%3BBattiloro%2C+Ciro%3BTufano%2C+Giovanni%3BCioffi%2C+Angela%3BGuardasole%2C+Vincenzo%3BAngelini%2C+Valentina%3BGuidetti%2C+Giovanna%3BBarbera%2C+Santi%3BRenda%2C+Francesco%3BRomano%2C+Francesco%3BVolpintesta%2C+Antonio%3BRobbiati%2C+Sergio+Federico%3BSannicol%C3%B2%2C+Mirella%3BFilipazzi%2C+Virginio%3BEsani%2C+Gabriella%3BGambaro%2C+Anna%3BFerrario%2C+Sabrina%3BTinessa%2C+Vincenza%3BCaprio%2C+Maria+Grazia%3BZonato%2C+Sabrina%3BCabiddu%2C+Mary%3BRaina%2C+Alberto%3BVeltri%2C+Enzo%3BD%27Aprile%2C+Modesto%3BPistillucci%2C+Giorgio%3BPorcile%2C+Gianfranco%3BOstellino%2C+Oliviero%3BVinante%2C+Orazio%3BAzzarello%2C+Giuseppe%3BGebbia%2C+Vittorio%3BBorsellino%2C+Nicola%3BTesta%2C+Antonio%3BGasparini%2C+Giampietro%3BMorabito%2C+Alessandra%3BGattuso%2C+Domenico%3BRomito%2C+Sante%3BCarrozza%2C+Francesco%3BFava%2C+Sergio%3BCalcagno%2C+Anna%3BGrimi%2C+Emanuela%3BBertetto%2C+Oscar%3BCiuffreda%2C+Libero%3BParello%2C+Giuseppe%3BMaiorino%2C+Luigi%3BSantoro%2C+Antonio%3BSantoro%2C+Massimiliano%3BFailla%2C+Giuseppe%3BAiello%2C+Rosa+Anna%3BBearz%2C+Alessandra%3BSorio%2C+Roberto%3BScalone%2C+Simona%3BClerici%2C+Maurizia%3BBollina%2C+Roberto%3BBelloni%2C+Paolo%3BSacco%2C+Cosimo%3BSibau%2C+Angela%3BAdamo%2C+Vincenzo%3BAltavilla%2C+Giuseppe%3BScimone%2C+Antonino%3BSpatafora%2C+Mario%3BBellia%2C+Vincenzo%3BHopps%2C+Maria+Raffealla%3BMonfardini%2C+Silvio%3BFavaretto%2C+Adolfo%3BStefani%2C+Micaela%3BCorradini%2C+Giuliana+Mara%3BPavia%2C+Gianfranco%3BScagliotti%2C+Giorgio%3BNovello%2C+Silvia%3BSelvaggi%2C+Giovanni%3BTonato%2C+Maurizio%3BDarwish%2C+Samir%3BMichetti%2C+Giovanni%3BBelometti%2C+Maria+Ori%3BLabianca%2C+Roberto%3BQuadri%2C+Antonello%3BDe+Marinis%2C+Filippo%3BMigliorino%2C+Maria+Rita%3BMartelli%2C+Olga%3BColucci%2C+Giuseppe%3BGaletta%2C+Dominico%3BGiotta%2C+Francesco%3BIsa%2C+Luciano%3BCandido%2C+Paola%3BRossi%2C+Nestore%3BCalandriello%2C+Antonio%3BFerra%C3%B9%2C+Francesco%3BMalaponte%2C+Emilia%3BBarni%2C+Sandro%3BCazzaniga%2C+Marina%3BGebbia%2C+Nicola%3BValerio%2C+Maria+Rosaria%3BBelli%2C+Mario%3BColantuoni%2C+Giuseppe%3BCapuano%2C+Matteo+Antonio%3BAngiolillo%2C+Michele%3BSollitto%2C+Francesco%3BArdizzoia%2C+Antonio%3BLuporini%2C+Gino%3BLocatelli%2C+Maria+Cristina%3BPari%2C+Franca%3BAitini%2C+Enrico%3BPedicini%2C+Tonino%3BFebbraro%2C+Antonio%3BZollo%2C+Cesira%3BDi+Costanzo%2C+Francesco%3BBartolucci%2C+Roberta%3BGasperoni%2C+Silvia%3BGaion%2C+Fernando%3BPalazzolo%2C+Giovanni%3BGalligioni%2C+Enzo%3BCaffo%2C+Orazio%3BCortesi%2C+Enrico%3BD%27Auria%2C+Giuliana%3BCurcio%2C+Carlo%3BVasta%2C+Matteo%3BBumma%2C+Cesare%3BCelano%2C+Alfredo%3BBretti%2C+Sergio%3BNettis%2C+Giuseppe%3BAnselmo%2C+Annamaria%3BMattioli%2C+Rodolfo%3BNistic%C3%B2%2C+Cecilia%3BAschelter%2C+Annamaria%3BFoa%2C+Paola&rft.aulast=Di+Maio&rft.aufirst=M&rft.date=2003-09-15&rft.volume=89&rft.issue=6&rft.spage=1013&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 - 2003-10-17 N1 - Date created - 2003-09-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Lancet Oncol. 2002 May;3(5):289-97 [12067806] J Natl Cancer Inst. 2003 Mar 5;95(5):362-72 [12618501] J Clin Oncol. 2003 Aug 15;21(16):3025-34 [12837810] J Chronic Dis. 1975 Jan;28(1):7-21 [1110265] IARC Sci Publ. 1980;(32):5-338 [7216345] Am J Clin Oncol. 1982 Dec;5(6):649-55 [7165009] Br J Cancer. 2001 Nov 30;85(11):1634-9 [11742480] DICP. 1990 Nov;24(11):1093-7 [2275235] BMJ. 1995 Oct 7;311(7010):899-909 [7580546] J Natl Cancer Inst. 1999 Jan 6;91(1):66-72 [9890172] Drug Saf. 2000 Feb;22(2):103-9 [10672893] Postgrad Med J. 2001 Nov;77(913):703-7 [11677279] Postgrad Med. 1989 Dec;86(8):179-86 [2685792] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impact of concomitant antiblastic chemotherapy and highly active antiretroviral therapy on human immunodeficiency virus (HIV) viremia and genotyping in HIV-infected patients with non-Hodgkin lymphoma. AN - 73633723; 12955644 AB - We evaluated the replication and resistance patterns of human immunodeficiency virus (HIV) strains recovered from HIV-infected patients with non-Hodgkin lymphoma (NHL) who were receiving chemotherapy (CT) concomitant with highly active antiretroviral therapy (HAART). We analyzed virological response to HAART in 35 patients with HIV and NHL who were treated with a cyclophosphamide-doxorubicin-vincristine-prednisone chemotherapy regimen and HAART and the virological response in 26 HIV-infected patients with CD20 cell-positive NHL who were treated with rituximab and cyclophosphamide-doxorubin-etoposide therapy. Genotype and virtual phenotype analyses were performed at baseline and when virological failure occurred. Only 9 patients met the criteria for virological failure. Genotype and virtual phenotype analyses demonstrated that, during CT administration, new mutations might occur, but there were no significant changes in the preexisting resistance patterns. Our data show that combination therapy consisting of CT and HAART is feasible and that the virological response can be maintained in the majority of patients receiving this treatment. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Simonelli, Cecilia AU - Zanussi, Stefania AU - Cinelli, Roberta AU - Dal Maso, Luigino AU - Di Gennaro, Giampiero AU - D'Andrea, Monica AU - Nasti, Guglielmo AU - Spina, Michele AU - Vaccher, Emanuela AU - De Paoli, Paolo AU - Tirelli, Umberto AD - Division of Medical Oncology A, National Cancer Institute, Aviano, Italy. Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 820 EP - 827 VL - 37 IS - 6 KW - Anti-HIV Agents KW - 0 KW - Antibodies, Monoclonal KW - Antibodies, Monoclonal, Murine-Derived KW - Rituximab KW - 4F4X42SYQ6 KW - Vincristine KW - 5J49Q6B70F KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Humans KW - Child KW - Antibodies, Monoclonal -- administration & dosage KW - Viral Load KW - Drug Therapy, Combination KW - Genotype KW - Adult KW - Antiretroviral Therapy, Highly Active KW - Middle Aged KW - Adolescent KW - HIV-1 -- drug effects KW - Female KW - Male KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Cyclophosphamide -- therapeutic use KW - Anti-HIV Agents -- therapeutic use KW - HIV Infections -- complications KW - Viremia -- drug therapy KW - Vincristine -- therapeutic use KW - Prednisone -- therapeutic use KW - Lymphoma, Non-Hodgkin -- complications KW - HIV Infections -- drug therapy KW - Viremia -- complications KW - Doxorubicin -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73633723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Impact+of+concomitant+antiblastic+chemotherapy+and+highly+active+antiretroviral+therapy+on+human+immunodeficiency+virus+%28HIV%29+viremia+and+genotyping+in+HIV-infected+patients+with+non-Hodgkin+lymphoma.&rft.au=Simonelli%2C+Cecilia%3BZanussi%2C+Stefania%3BCinelli%2C+Roberta%3BDal+Maso%2C+Luigino%3BDi+Gennaro%2C+Giampiero%3BD%27Andrea%2C+Monica%3BNasti%2C+Guglielmo%3BSpina%2C+Michele%3BVaccher%2C+Emanuela%3BDe+Paoli%2C+Paolo%3BTirelli%2C+Umberto&rft.aulast=Simonelli&rft.aufirst=Cecilia&rft.date=2003-09-15&rft.volume=37&rft.issue=6&rft.spage=820&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-21 N1 - Date created - 2003-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) activity of the antimutagenic human MTH1 protein by nucleoside 5'-diphosphates. AN - 73624843; 12957652 AB - The hMTH1 protein, a human homologue of E. coli MutT protein, is an enzyme converting 8-oxo-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) to 8-oxo-2'-deoxyguanosine 5'-monophosphate (8-oxo-dGMP) and inorganic pyrophosphate. It is thought to play an antimutagenic role by preventing the incorporation of promutagenic 8-oxo-dGTP into DNA. As found in our previous investigations, 8-oxo-2'-deoxyguanosine 5'-diphosphate (8-oxo-dGDP) strongly inhibited 8-oxo-dGTPase activity of MTH1. Following this finding, in the present study we have tested the canonical ribo- and deoxyribonucleoside 5'-diphosphates (NDPs and dNDPs) for possible inhibition of 8-oxo-dGTP hydrolysis by hMTH1 extracted from CCRF-CEM cells (a human leukemia cell line). Among them, the strongest inhibitors appeared to be dGDP (Ki=74 microM), dADP (Ki=147 microM), and GDP (Ki=502 microM). Other dNDPs and NDPs, such as dCDP, dTDP, ADP, CDP, and UDP were much weaker inhibitors, with Ki in the millimolar range. Based on the present results and published data, we estimate that the strongest inhibitors, dGDP and dADP, at physiological concentrations not exceeding 5 microM and GDP at mean concentration of 30 microM, taken together, can decrease the cellular hMTH1 enzymatic activity vs. 8-oxo-dGTP (expected to remain below 500 pM) by up to 15%. The other five NDPs and dNDPs tested cannot markedly affect this activity. JF - Free radical biology & medicine AU - Bialkowski, Karol AU - Kasprzak, Kazimierz S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD, USA. karolb@amb.bydgoszcz.pl Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 595 EP - 602 VL - 35 IS - 6 SN - 0891-5849, 0891-5849 KW - Deoxyguanine Nucleotides KW - 0 KW - Nucleotides KW - deoxyguanosine triphosphate KW - 8C2O37Y44Q KW - Oxidoreductases Acting on CH-NH Group Donors KW - EC 1.5.- KW - methylenetetrahydromethanopterin dehydrogenase KW - EC 1.5.99.- KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - 8-oxodGTPase KW - EC 3.6.1.55 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Kinetics KW - Humans KW - Cell Line, Tumor KW - Substrate Specificity KW - Chromatography, High Pressure Liquid KW - Deoxyguanine Nucleotides -- pharmacology KW - Oxidoreductases Acting on CH-NH Group Donors -- metabolism KW - Oxidoreductases Acting on CH-NH Group Donors -- antagonists & inhibitors KW - Nucleotides -- pharmacology KW - Phosphoric Monoester Hydrolases -- metabolism KW - Phosphoric Monoester Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73624843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Inhibition+of+8-oxo-2%27-deoxyguanosine+5%27-triphosphate+pyrophosphohydrolase+%288-oxo-dGTPase%29+activity+of+the+antimutagenic+human+MTH1+protein+by+nucleoside+5%27-diphosphates.&rft.au=Bialkowski%2C+Karol%3BKasprzak%2C+Kazimierz+S&rft.aulast=Bialkowski&rft.aufirst=Karol&rft.date=2003-09-15&rft.volume=35&rft.issue=6&rft.spage=595&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-12 N1 - Date created - 2003-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crucial role of IL-4/STAT6 in T cell-mediated hepatitis: up-regulating eotaxins and IL-5 and recruiting leukocytes. AN - 73619813; 12960353 AB - T cell-mediated immune responses are implicated in the pathogenesis of a variety of liver disorders; however, the underlying mechanism remains obscure. Con A injection is a widely accepted mouse model to study T cell-mediated liver injury, in which STAT6 is rapidly activated. Disruption of the IL-4 and STAT6 gene by way of genetic knockout abolishes Con A-mediated liver injury without affecting IFN-gamma/STAT1, IL-6/STAT3, or TNF-alpha/NF-kappaB signaling or affecting NKT cell activation. Infiltration of neutrophils and eosinophils in Con A-induced hepatitis is markedly suppressed in IL-4 (-/-) and STAT6(-/-) mice compared with wild-type mice. IL-4 treatment induces expression of eotaxins in hepatocytes and sinusoidal endothelial cells isolated from wild-type mice but not from STAT6(-/-) mice. Con A injection induces expression of eotaxins in the liver and elevates serum levels of IL-5 and eotaxins; such induction is markedly attenuated in IL-4(-/-) and STAT6(-/-) mice. Finally, eotaxin blockade attenuates Con A-induced liver injury and leukocyte infiltration. Taken together, these findings suggest that IL-4/STAT6 plays a critical role in Con A-induced hepatitis, via enhancing expression of eotaxins in hepatocytes and sinusoidal endothelial cells, and induces IL-5 expression, thereby facilitating recruitment of eosinophils and neutrophils into the liver and resulting in hepatitis. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Jaruga, Barbara AU - Hong, Feng AU - Sun, Rui AU - Radaeva, Svetlana AU - Gao, Bin AD - Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 3233 EP - 3244 VL - 171 IS - 6 SN - 0022-1767, 0022-1767 KW - Ccl11 protein, mouse KW - 0 KW - Chemokine CCL11 KW - Chemokines, CC KW - DNA-Binding Proteins KW - Immune Sera KW - Interleukin-5 KW - NF-kappa B KW - STAT1 Transcription Factor KW - STAT3 Transcription Factor KW - STAT6 Transcription Factor KW - Stat1 protein, mouse KW - Stat3 protein, mouse KW - Stat6 protein, mouse KW - Trans-Activators KW - Tumor Necrosis Factor-alpha KW - Concanavalin A KW - 11028-71-0 KW - Interleukin-4 KW - 207137-56-2 KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Concanavalin A -- administration & dosage KW - Liver -- immunology KW - Liver -- metabolism KW - Mice, Inbred BALB C KW - Mice, Knockout KW - Neutrophil Infiltration -- immunology KW - Lymphocyte Activation -- genetics KW - Leukocytes, Mononuclear -- transplantation KW - Immune Sera -- administration & dosage KW - Eosinophils -- pathology KW - Spleen -- immunology KW - Signal Transduction -- immunology KW - Male KW - Liver -- pathology KW - Injections, Intravenous KW - Spleen -- metabolism KW - Up-Regulation -- genetics KW - Tumor Necrosis Factor-alpha -- physiology KW - Mice KW - NF-kappa B -- physiology KW - Adoptive Transfer KW - Neutrophil Infiltration -- genetics KW - Cells, Cultured KW - Signal Transduction -- genetics KW - Mice, Inbred C57BL KW - Interferon-gamma -- physiology KW - DNA-Binding Proteins -- physiology KW - Up-Regulation -- immunology KW - Killer Cells, Natural -- immunology KW - Interleukin-4 -- genetics KW - Trans-Activators -- metabolism KW - Trans-Activators -- deficiency KW - Hepatitis, Animal -- pathology KW - Hepatitis, Animal -- chemically induced KW - Cell Movement -- immunology KW - Hepatitis, Animal -- immunology KW - Interleukin-4 -- deficiency KW - Cell Movement -- genetics KW - Interleukin-5 -- biosynthesis KW - Trans-Activators -- genetics KW - Leukocytes -- pathology KW - T-Lymphocyte Subsets -- immunology KW - Chemokines, CC -- antagonists & inhibitors KW - Hepatitis, Animal -- genetics KW - Trans-Activators -- physiology KW - Chemokines, CC -- biosynthesis KW - Interleukin-4 -- physiology KW - Chemokines, CC -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73619813?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Crucial+role+of+IL-4%2FSTAT6+in+T+cell-mediated+hepatitis%3A+up-regulating+eotaxins+and+IL-5+and+recruiting+leukocytes.&rft.au=Jaruga%2C+Barbara%3BHong%2C+Feng%3BSun%2C+Rui%3BRadaeva%2C+Svetlana%3BGao%2C+Bin&rft.aulast=Jaruga&rft.aufirst=Barbara&rft.date=2003-09-15&rft.volume=171&rft.issue=6&rft.spage=3233&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 - 2003-12-04 N1 - Date created - 2003-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of copper chelation agents as anti-angiogenic therapy. AN - 73605225; 12951159 AB - The design, synthesis and evaluation of N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5,-triaminocyclohexane (tachpyr, 1) derivatives as novel anti-angiogenic agents were performed in an in vitro endothelial cell proliferation assay to assess their cytotoxicity and selectivity. The selective nature of the anti-angiogenic agents for human umbilical vein endothelial cells (Huvec) was compared to a normal fibroblast cell line and a human Glioma cell line to evaluate these compounds. N,N',N"-tris(2-mercaptoethyl)-cis,cis-1,3,5-triaminocyclohexane trihydrochloride (3b) was superior to tachpyr in terms of selectivity of its inhibitory activity toward the proliferation of Huvec compared to the fibroblast and human Glioma cell lines. JF - Bioorganic & medicinal chemistry AU - Camphausen, Kevin AU - Sproull, Mary AU - Tantama, Steve AU - Sankineni, Sandeep AU - Scott, Tamalee AU - Ménard, Cynthia AU - Coleman, C Norman AU - Brechbiel, Martin W AD - Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10, Room B3B69, Bethesda, MD 20892-1002, USA. Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 4287 EP - 4293 VL - 11 IS - 19 SN - 0968-0896, 0968-0896 KW - Angiogenesis Inhibitors KW - 0 KW - Chelating Agents KW - Cyclohexylamines KW - Pyridines KW - tachpyr KW - Copper KW - 789U1901C5 KW - Index Medicus KW - Endothelial Cells -- drug effects KW - Dose-Response Relationship, Drug KW - Cells, Cultured KW - Humans KW - Umbilical Veins KW - Cell Division -- drug effects KW - Cell Line, Tumor KW - Inhibitory Concentration 50 KW - Glioma KW - Drug Design KW - Cell Line KW - Fibroblasts KW - Angiogenesis Inhibitors -- therapeutic use KW - Chelating Agents -- pharmacology KW - Angiogenesis Inhibitors -- pharmacology KW - Pyridines -- chemical synthesis KW - Chelating Agents -- therapeutic use KW - Chelating Agents -- chemical synthesis KW - Pyridines -- therapeutic use KW - Angiogenesis Inhibitors -- chemical synthesis KW - Cyclohexylamines -- pharmacology KW - Pyridines -- pharmacology KW - Cyclohexylamines -- chemical synthesis KW - Copper -- chemistry KW - Cyclohexylamines -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73605225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry&rft.atitle=Evaluation+of+copper+chelation+agents+as+anti-angiogenic+therapy.&rft.au=Camphausen%2C+Kevin%3BSproull%2C+Mary%3BTantama%2C+Steve%3BSankineni%2C+Sandeep%3BScott%2C+Tamalee%3BM%C3%A9nard%2C+Cynthia%3BColeman%2C+C+Norman%3BBrechbiel%2C+Martin+W&rft.aulast=Camphausen&rft.aufirst=Kevin&rft.date=2003-09-15&rft.volume=11&rft.issue=19&rft.spage=4287&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry&rft.issn=09680896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-25 N1 - Date created - 2003-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acylsulfonamide-containing PTP1B inhibitors designed to mimic an enzyme-bound water of hydration. AN - 73595117; 12941322 AB - Previously, it had been reported that 6-(phosphonodifluoromethyl)-2-naphthoic acid binds to the protein-tyrosine phosphatase PTP1B with its 2-carboxyl group interacting only indirectly through a bridging water molecule. Reported herein is a family of new analogues that utilize acylsulfonamido functionality both to mimic this water of hydration and to provide an additional new site for elaboration not found in the parent carboxyl-containing analogue. Target acylsulfonamides were prepared in two steps from commercially available primary sulfonamides, which were selected based on in silico screening for their potential ability to interact with one of three binding surfaces proximal to the PTP1B catalytic site. In general, modest potency enhancements were observed. Arylacylsulfonamides represent a structure-based extension of inhibitor design that may have broader utility in the development of PTP1B inhibitors. JF - Bioorganic & medicinal chemistry letters AU - Liu, Ding-Guo AU - Gao, Yang AU - Voigt, Johannes H AU - Lee, Kyeong AU - Nicklaus, Marc C AU - Wu, Li AU - Zhang, Zhong-Yin AU - Burke, Terrence R AD - Laboratory of Medicinal Chemistry, CCR, NCI, NIH, NCI-Frederick, Frederick, MD 21702, USA. Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 3005 EP - 3007 VL - 13 IS - 18 SN - 0960-894X, 0960-894X KW - Amino Acids, Acidic KW - 0 KW - Enzyme Inhibitors KW - Enzymes KW - Sulfonamides KW - Water KW - 059QF0KO0R KW - PTPN1 protein, human KW - EC 3.1.3.48 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 1 KW - Protein Tyrosine Phosphatases KW - Index Medicus KW - Animals KW - Computer Simulation KW - Enzymes -- chemistry KW - Humans KW - Amino Acids, Acidic -- chemistry KW - Water -- chemistry KW - Molecular Mimicry KW - Inhibitory Concentration 50 KW - Protein Binding KW - Structure-Activity Relationship KW - Binding Sites KW - Enzyme Inhibitors -- chemistry KW - Enzyme Inhibitors -- pharmacology KW - Drug Design KW - Protein Tyrosine Phosphatases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73595117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry+letters&rft.atitle=Acylsulfonamide-containing+PTP1B+inhibitors+designed+to+mimic+an+enzyme-bound+water+of+hydration.&rft.au=Liu%2C+Ding-Guo%3BGao%2C+Yang%3BVoigt%2C+Johannes+H%3BLee%2C+Kyeong%3BNicklaus%2C+Marc+C%3BWu%2C+Li%3BZhang%2C+Zhong-Yin%3BBurke%2C+Terrence+R&rft.aulast=Liu&rft.aufirst=Ding-Guo&rft.date=2003-09-15&rft.volume=13&rft.issue=18&rft.spage=3005&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry+letters&rft.issn=0960894X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-21 N1 - Date created - 2003-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chlamydia trachomatis uses host cell dynein to traffic to the microtubule-organizing center in a p50 dynamitin-independent process AN - 19227723; 5788633 AB - Chlamydiae are pathogenic obligate intracellular bacteria with a biphasic developmental cycle that involves cell types adapted for extracellular survival (elementary bodies, EBs) and intracellular multiplication (reticulate bodies, RBs). The intracellular development of chlamydiae occurs entirely within a membrane-bound vacuole termed an inclusion. Within 2 hours after entry into host cells, Chlamydia trachomatis EBs are trafficked to the perinuclear region of the host cell and remain in close proximity to the Golgi apparatus, where they begin to fuse with a subset of host vesicles containing sphingomyelin. Here, we provide evidence that chlamydial migration from the cell periphery to the peri-Golgi region resembles host cell vesicular trafficking. Chlamydiae move towards the minus end of microtubules and aggregate at the microtubule-organizing center (MTOC). In mammalian cells the most important minus-end-directed microtubule motor is cytoplasmic dynein. Microinjection of antibodies to a subunit of cytoplasmic dynein inhibited movement of chlamydiae to the MTOC, whereas microinjection of antibodies to the plus-directed microtubule motor, kinesin, had no effect. Surprisingly, overexpression of the protein p50 dynamitin, a subunit of the dynactin complex that links vesicular cargo to the dynein motor in minus directed vesicle trafficking, did not abrogate chlamydial migration even though host vesicle transport was inhibited. Nascent chlamydial inclusions did, however, colocalize with the p150 super((Glued)) dynactin subunit, which suggests that p150 super((Glued)) may be required for dynein activation or processivity but that the cargo-binding activity of dynactin, supplied by p50 dynamitin subunits and possibly other subunits, is not. Because chlamydial transcription and translation were required for this intracellular trafficking, chlamydial proteins modifying the cytoplasmic face of the inclusion membrane are probable candidates for proteins fulfilling this function. JF - Journal of Cell Science AU - Grieshaber, S S AU - Grieshaber, NA AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, NIAID, NIH, Rocky Mountain Laboratories, Hamilton, MT 59840, USA, ted_hackstadt@nih.gov Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 3793 EP - 3802 VL - 116 IS - 18 SN - 0021-9533, 0021-9533 KW - elementary bodies KW - dynamitin KW - Microbiology Abstracts B: Bacteriology KW - Translation KW - Golgi apparatus KW - Microtubules KW - Dynein KW - Proteins KW - Transcription KW - Chlamydia trachomatis KW - dynactin KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19227723?accountid=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+Cell+Science&rft.atitle=Chlamydia+trachomatis+uses+host+cell+dynein+to+traffic+to+the+microtubule-organizing+center+in+a+p50+dynamitin-independent+process&rft.au=Grieshaber%2C+S+S%3BGrieshaber%2C+NA%3BHackstadt%2C+T&rft.aulast=Grieshaber&rft.aufirst=S&rft.date=2003-09-15&rft.volume=116&rft.issue=18&rft.spage=3793&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cell+Science&rft.issn=00219533&rft_id=info:doi/10.1242%2Fjcs.00695 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Golgi apparatus; Transcription; Translation; Proteins; Dynein; Microtubules; dynactin DO - http://dx.doi.org/10.1242/jcs.00695 ER - TY - JOUR T1 - Chemical-specific alterations in ras, p53, and beta -catenin genes in hemangiosarcomas from B6C3F1 mice exposed to o-nitrotoluene or riddelliine for 2 years AN - 18897632; 5754486 AB - The most prominent neoplastic lesions in mice in the 2-year studies of o-nitrotoluene and riddelliine were hemangiosarcomas. Fifteen o-nitrotoluene-induced hemangiosarcomas of the skeletal muscle, subcutaneous tissue, and mesentery; 12 riddelliine-induced hemangiosarcomas of the liver; and 15 spontaneous subcutaneous hemangiosarcomas were examined for genetic alterations in ras, p53, and beta -catenin genes. Mutations in at least one of these genes were identified in 13 of 15 (87%) of the o-nitrotoluene-induced hemangiosarcomas with missense mutations in p53 exons 5-8 detected in 11 of 15 (73%) of these neoplasms. Seven of 15 (47%) hemangiosarcomas from mice exposed to o-nitrotoluene had deletions at exon 2 splice sites or smaller deletions in the beta -catenin gene. K-ras mutation was detected in only 1 of the 15 (7%) o-nitrotoluene-induced hemangiosarcomas. In contrast to the o-nitrotoluene study, 7/12 (58%) riddelliine-induced hemangiosarcomas had K-ras codon 12 GTT mutations and, when screened by immunohistochemistry, 9/12 (75%) had strong staining for the p53 protein in malignant endothelial cells, the cells of origin of hemangiosarcomas. Riddelliine-induced hemangiosarcomas were negative for the beta -catenin protein. Spontaneous hemangiosarcomas from control mice lacked both p53 and beta -catenin protein expression and ras mutations. Our data indicated that p53 and beta -catenin mutations in the o-nitrotoluene-induced hemangiosarcomas and K-ras mutations and p53 protein expression in riddelliine-induced hemangiosarcomas most likely occurred as a result of the genotoxic effects of these chemicals. It also suggests that these mutations play a role in the pathogenesis of the respective hemangiosarcomas in B6C3F11 mice. JF - Toxicology and Applied Pharmacology AU - Hong, H L AU - Ton, T V AU - Devereux, T R AU - Moomaw, C AU - Clayton, N AU - Chan, P AU - Dunnick, J K AU - Sills, R C AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA, hong@niehs.nih.gov Y1 - 2003/09/15/ PY - 2003 DA - 2003 Sep 15 SP - 227 EP - 234 PB - Elsevier Inc. VL - 191 IS - 3 SN - 0041-008X, 0041-008X KW - beta -Catenin KW - mice KW - nitrotoluene KW - ras protein KW - Toxicology Abstracts KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18897632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Chemical-specific+alterations+in+ras%2C+p53%2C+and+beta+-catenin+genes+in+hemangiosarcomas+from+B6C3F1+mice+exposed+to+o-nitrotoluene+or+riddelliine+for+2+years&rft.au=Hong%2C+H+L%3BTon%2C+T+V%3BDevereux%2C+T+R%3BMoomaw%2C+C%3BClayton%2C+N%3BChan%2C+P%3BDunnick%2C+J+K%3BSills%2C+R+C&rft.aulast=Hong&rft.aufirst=H&rft.date=2003-09-15&rft.volume=191&rft.issue=3&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1016%2FS0041-008X%2803%2900165-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0041-008X(03)00165-0 ER - TY - JOUR T1 - Cholecystokinin-stimulated protein kinase C-delta kinase activation, tyrosine phosphorylation, and translocation are mediated by Src tyrosine kinases in pancreatic acinar cells. AN - 73633329; 12842900 AB - Protein kinase C-delta (PKC-delta) is involved in growth, differentiation, tumor suppression, and regulation of other cellular processes. PKC-delta activation causes translocation, tyrosine phosphorylation, and serine-threonine kinase activity. However, little is known about the ability of G protein-coupled receptors to activate these processes or the mediators involved. In the present study, we explored the ability of the neurotransmitter/hormone, CCK, to stimulate these changes in PKC-delta and explored the mechanisms. In rat pancreatic acini under basal conditions, PKC-delta is almost exclusively located in cytosol. CCK and TPA stimulated a rapid PKC-delta translocation to membrane and nuclear fractions, which was transient with CCK. CCK stimulated rapid tyrosine phosphorylation of PKC-delta and increased kinase activity. Using tyrosine kinase (B44) and a tyrosine phosphatase inhibitor (orthovanadate), changes in both CCK- and TPA-stimulated PKC-delta tyrosine phosphorylation were shown to correlate with changes in its kinase activity but not translocation. Both PKC-delta tyrosine phosphorylation and activation occur exclusively in particulate fractions. The Src kinase inhibitors, SU6656 and PP2, but not the inactive related compound, PP3, inhibited CCK- and TPA-stimulated PKC-delta tyrosine phosphorylation and activation. In contrast, PP2 also had a lesser effect on CCK- but not TPA-stimulated PKC-delta translocation. CCK stimulated the association of Src kinases with PKC-delta, demonstrated by co-immunoprecipitation. These results demonstrate that CCKA receptor activation results in rapid translocation, tyrosine phosphorylation, and activation of PKC-delta. Stimulation of PKC-delta translocation precedes tyrosine phosphorylation, which is essential for activation to occur. Activation of Src kinases is essential for the tyrosine phosphorylation and kinase activation to occur and plays a partial role in translocation. JF - The Journal of biological chemistry AU - Tapia, Jose A AU - García-Marin, Luis J AU - Jensen, Robert T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1804, USA. Y1 - 2003/09/12/ PY - 2003 DA - 2003 Sep 12 SP - 35220 EP - 35230 VL - 278 IS - 37 SN - 0021-9258, 0021-9258 KW - Enzyme Inhibitors KW - 0 KW - Tyrphostins KW - Phosphotyrosine KW - 21820-51-9 KW - Prkcd protein, rat KW - EC 2.7.1.- KW - src-Family Kinases KW - EC 2.7.10.2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Sincalide KW - M03GIQ7Z6P KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Cell Membrane -- enzymology KW - Cytosol -- enzymology KW - Protein Transport -- drug effects KW - Rats KW - Cell Fractionation KW - Cell Nucleus -- enzymology KW - Phosphorylation KW - Kinetics KW - Rats, Wistar KW - Enzyme Activation -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Tyrphostins -- pharmacology KW - Male KW - Protein Kinase C -- metabolism KW - src-Family Kinases -- metabolism KW - Phosphotyrosine -- metabolism KW - Pancreas -- enzymology KW - src-Family Kinases -- antagonists & inhibitors KW - Sincalide -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73633329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cholecystokinin-stimulated+protein+kinase+C-delta+kinase+activation%2C+tyrosine+phosphorylation%2C+and+translocation+are+mediated+by+Src+tyrosine+kinases+in+pancreatic+acinar+cells.&rft.au=Tapia%2C+Jose+A%3BGarc%C3%ADa-Marin%2C+Luis+J%3BJensen%2C+Robert+T&rft.aulast=Tapia&rft.aufirst=Jose&rft.date=2003-09-12&rft.volume=278&rft.issue=37&rft.spage=35220&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 - 2003-11-12 N1 - Date created - 2003-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Micromanipulation of the Chlamydia pneumoniae inclusion: implications for cloning and host-pathogen interactions AN - 19157370; 5753470 AB - The Chlamydia trachomatis inclusion is fragile, rendering it incompatible to micromanipulation. We show that the Chlamydia pneumoniae inclusion differs, being resistant to micromanipulation as shown by direct microinjection of the infected host cytosol or the inclusion itself. We have used micromanipulation to clone C. pneumoniae and to free it from mycoplasma contamination. JF - FEMS Microbiology Letters AU - Gieffers, J AU - Tamplin, V AU - Maass, M AU - Belland, R J AU - Caldwell, H D AD - Laboratory of Intracellular Parasites, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Hamilton, MT 59840, USA, jens.gieffers@hygiene.ukl.mu-luebeck.de Y1 - 2003/09/12/ PY - 2003 DA - 2003 Sep 12 SP - 45 EP - 49 PB - Federation of European Microbiological Societies VL - 226 IS - 1 SN - 0378-1097, 0378-1097 KW - micromanipulation KW - Microbiology Abstracts B: Bacteriology KW - Host-pathogen interactions KW - Chlamydia pneumoniae KW - Cloning KW - Microinjection KW - J 02704:Enumeration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19157370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=Micromanipulation+of+the+Chlamydia+pneumoniae+inclusion%3A+implications+for+cloning+and+host-pathogen+interactions&rft.au=Gieffers%2C+J%3BTamplin%2C+V%3BMaass%2C+M%3BBelland%2C+R+J%3BCaldwell%2C+H+D&rft.aulast=Gieffers&rft.aufirst=J&rft.date=2003-09-12&rft.volume=226&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/10.1016%2FS0378-1097%2803%2900563-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia pneumoniae; Host-pathogen interactions; Cloning; Microinjection DO - http://dx.doi.org/10.1016/S0378-1097(03)00563-9 ER - TY - JOUR T1 - Structural Evidence for Iron-free Citrate and Ferric Citrate Binding to the TonB-dependent Outer Membrane Transporter FecA AN - 18871959; 5726530 AB - Escherichia coli possesses a TonB-dependent transport system, which exploits the iron-binding capacity of citrate and its natural abundance. Here, we describe three structures of the outer membrane ferric citrate transporter FecA: unliganded and complexed with iron-free or diferric dicitrate. We show the structural mechanism for discrimination between the iron-free and ferric siderophore: the binding of diferric dicitrate, but not iron-free dicitrate alone, causes major conformational rearrangements in the transporter. The structure of FecA bound with iron-free dicitrate represents the first structure of a TonB-dependent transporter bound with an iron-free siderophore. Binding of diferric dicitrate to FecA results in changes in the orientation of the two citrate ions relative to each other and in their interactions with FecA, compared to the binding of iron-free dicitrate. The changes in ligand binding are accompanied by conformational changes in three areas of FecA: two extracellular loops, one plug domain loop and the periplasmic TonB-box motif. The positional and conformational changes in the siderophore and transporter initiate two independent events: ferric citrate transport into the periplasm and transcription induction of the fecABCDE transport genes. From these data, we propose a two-step ligand recognition event: FecA binds iron-free dicitrate in the non-productive state or first step, followed by siderophore displacement to form the transport-competent, diferric dicitrate-bound state in the second step. JF - Journal of Molecular Biology AU - Yue, W W AU - Grizot, S AU - Buchanan, S K AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA, skbuchan@helix.nih.gov Y1 - 2003/09/12/ PY - 2003 DA - 2003 Sep 12 SP - 353 EP - 368 VL - 332 IS - 2 SN - 0022-2836, 0022-2836 KW - FecA protein KW - TonB protein KW - siderophores KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18871959?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Structural+Evidence+for+Iron-free+Citrate+and+Ferric+Citrate+Binding+to+the+TonB-dependent+Outer+Membrane+Transporter+FecA&rft.au=Yue%2C+W+W%3BGrizot%2C+S%3BBuchanan%2C+S+K&rft.aulast=Yue&rft.aufirst=W&rft.date=2003-09-12&rft.volume=332&rft.issue=2&rft.spage=353&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1016%2FS0022-2836%2803%2900855-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0022-2836(03)00855-6 ER - TY - JOUR T1 - Modulation of 5-HT3 receptor-mediated response and trafficking by activation of protein kinase C. AN - 73627467; 12791692 AB - Modulation of neurotransmitter-gated membrane ion channels by protein kinase C (PKC) has been the subject of a number of studies. However, less is known about PKC modulation of the serotonin type 3 (5-HT3) receptor, a ligand-gated membrane ion channel that can mediate fast synaptic transmission in the central and peripheral nervous system. Here, we show that PKC potentiated 5-HT3 receptor-mediated current in Xenopus oocytes expressing 5-HT3A receptors and mouse N1E-115 neuroblastoma cells. In addition, using a specific antibody directed to the extracellular N-terminal domain of the 5-HT3A receptor, treatment with the PKC activator, 4 beta-phorbol 12-myristate 13-acetate (PMA), significantly increased surface immunofluorescence. PKC also increased the amount of 5-HT3A receptor protein in the cell membrane without affecting the amount receptor protein in the total cell extract. The magnitude of PMA potentiation of 5-HT3A receptor-mediated responses is correlated with the magnitude of PMA enhancement of the receptor abundance in the cell surface membrane. PMA potentiation is unlikely to occur via direct phosphorylation of the 5-HT3A receptor protein since the potentiation was not affected by point mutation of each of the putative sites for PKC phosphorylation. However, preapplication of phalloidin, which stabilizes the actin polymerization, significantly inhibited PMA potentiation of 5-HT-activated responses in both N1E-115 cells and oocytes expressing 5-HT3A receptors. On the other hand, latrunculin-A, which destabilizes actin cytoskeleton, enhanced the PMA potentiation of 5-HT3A receptors. The observations suggest that PKC can modulate 5-HT3A receptor function and trafficking through an F-actin-dependent mechanism. JF - The Journal of biological chemistry AU - Sun, Hui AU - Hu, Xian-Qun AU - Moradel, Edgar M AU - Weight, Forrest F AU - Zhang, Li AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-8115, USA. Y1 - 2003/09/05/ PY - 2003 DA - 2003 Sep 05 SP - 34150 EP - 34157 VL - 278 IS - 36 SN - 0021-9258, 0021-9258 KW - Actins KW - 0 KW - Bridged Bicyclo Compounds, Heterocyclic KW - Ions KW - RNA, Complementary KW - Receptors, Serotonin KW - Receptors, Serotonin, 5-HT3 KW - Thiazoles KW - Thiazolidines KW - Phalloidine KW - 17466-45-4 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - latrunculin A KW - SRQ9WWM084 KW - Index Medicus KW - Animals KW - Humans KW - Actins -- metabolism KW - Microscopy, Fluorescence KW - Bridged Bicyclo Compounds, Heterocyclic -- chemistry KW - Tumor Cells, Cultured KW - Phosphorylation KW - Point Mutation KW - Xenopus KW - Time Factors KW - Thiazoles -- chemistry KW - Cytoskeleton -- metabolism KW - Enzyme Activation KW - Phalloidine -- chemistry KW - Mice KW - Electrophysiology KW - RNA, Complementary -- metabolism KW - Binding Sites KW - Xenopus laevis KW - Blotting, Western KW - Oocytes -- metabolism KW - Cell Membrane -- metabolism KW - Protein Structure, Tertiary KW - Mutation KW - Actins -- chemistry KW - Protein Transport KW - Protein Kinase C -- metabolism KW - Receptors, Serotonin -- chemistry KW - Receptors, Serotonin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73627467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modulation+of+5-HT3+receptor-mediated+response+and+trafficking+by+activation+of+protein+kinase+C.&rft.au=Sun%2C+Hui%3BHu%2C+Xian-Qun%3BMoradel%2C+Edgar+M%3BWeight%2C+Forrest+F%3BZhang%2C+Li&rft.aulast=Sun&rft.aufirst=Hui&rft.date=2003-09-05&rft.volume=278&rft.issue=36&rft.spage=34150&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 - 2003-10-07 N1 - Date created - 2003-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Compromised incision of oxidized pyrimidines in liver mitochondria of mice deficient in NTH1 and OGG1 glycosylases. AN - 73611970; 12819227 AB - Mitochondrial DNA is constantly exposed to high levels of endogenously produced reactive oxygen species, resulting in elevated levels of oxidative damaged DNA bases. A large spectrum of DNA base alterations can be detected after oxidative stress, and many of these are highly mutagenic. Thus, an efficient repair of these is necessary for survival. Some of the DNA repair pathways involved have been characterized, but others are not yet determined. A DNA repair activity for thymine glycol and other oxidized pyrimidines has been described in mammalian mitochondria, but the nature of the glycosylases involved in this pathway remains unclear. The generation of mouse strains lacking murine thymine glycol-DNA glycosylase (mNTH1) and/or murine 8-oxoguanine-DNA glycosylase (mOGG1), the two major DNA N-glycosylase/apurinic/apyrimidinic (AP) lyases involved in the repair of oxidative base damage in the nucleus, has provided very useful biological model systems for the study of the function of these and other glycosylases in mitochondrial DNA repair. In this study, mouse liver mitochondrial extracts were generated from mNTH1-, mOGG1-, and [mNTH1, mOGG1]-deficient mice to ascertain the role of each of these glycosylases in the repair of oxidized pyrimidine base damage. We also characterized for the first time the incision of various modified bases in mitochondrial extracts from a double-knock-out [mNTH1, mOGG1]-deficient mouse. We show that mNTH1 is responsible for the repair of thymine glycols in mitochondrial DNA, whereas other glycosylase/AP lyases also participate in removing other oxidized pyrimidines, such as 5-hydroxycytosine and 5-hydroxyuracil. We did not detect a backup glycosylase or glycosylase/AP lyase activity for thymine glycol in the mitochondrial mouse extracts. JF - The Journal of biological chemistry AU - Karahalil, Bensu AU - de Souza-Pinto, Nadja C AU - Parsons, Jason L AU - Elder, Rhoderick H AU - Bohr, Vilhelm A AD - Laboratory of Molecular Gerontology, National Institute on Aging,, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2003/09/05/ PY - 2003 DA - 2003 Sep 05 SP - 33701 EP - 33707 VL - 278 IS - 36 SN - 0021-9258, 0021-9258 KW - Borohydrides KW - 0 KW - Escherichia coli Proteins KW - Oligonucleotides KW - Pyrimidines KW - Reactive Oxygen Species KW - Uracil KW - 56HH86ZVCT KW - sodium borohydride KW - 87L0B9CPPA KW - Endodeoxyribonucleases KW - EC 3.1.- KW - Deoxyribonuclease (Pyrimidine Dimer) KW - EC 3.1.25.1 KW - NTH protein, E coli KW - Nth1 protein, mouse KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - DNA-Formamidopyrimidine Glycosylase KW - EC 3.2.2.23 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - DNA Repair KW - Uracil -- chemistry KW - Cell Nucleus -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Endodeoxyribonucleases -- genetics KW - Liver -- metabolism KW - Mice KW - Endodeoxyribonucleases -- physiology KW - Mice, Knockout KW - Base Sequence KW - Blotting, Western KW - Borohydrides -- pharmacology KW - Oligonucleotides -- chemistry KW - Oxidative Stress KW - Molecular Sequence Data KW - Pyrimidines -- chemistry KW - N-Glycosyl Hydrolases -- genetics KW - Oxygen -- metabolism KW - Mitochondria, Liver -- metabolism KW - N-Glycosyl Hydrolases -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73611970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Compromised+incision+of+oxidized+pyrimidines+in+liver+mitochondria+of+mice+deficient+in+NTH1+and+OGG1+glycosylases.&rft.au=Karahalil%2C+Bensu%3Bde+Souza-Pinto%2C+Nadja+C%3BParsons%2C+Jason+L%3BElder%2C+Rhoderick+H%3BBohr%2C+Vilhelm+A&rft.aulast=Karahalil&rft.aufirst=Bensu&rft.date=2003-09-05&rft.volume=278&rft.issue=36&rft.spage=33701&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 - 2003-10-07 N1 - Date created - 2003-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kinetics of Intramolecular Contact Formation in a Denatured Protein AN - 21286613; 5726508 AB - Quenching of the triplet state of tryptophan by cysteine has provided a new tool for measuring the rate of forming a specific intramolecular contact in disordered polypeptides. Here, we use this technique to investigate contact formation in the denatured state of CspTm, a small cold-shock protein from Thermotoga maritima, engineered to contain a single tryptophan residue (W29) and a single cysteine residue at the C terminus (C67). At all concentrations of denaturant, the decay rate of the W29 triplet of the unfolded protein is more than tenfold faster than the rate observed for the native protein (~10 super(4)s super(-1)). Experiments on the unfolded protein without the added C-terminal cysteine residue show that this faster rate results entirely from contact quenching by C67. The quenching rate in the unfolded state by C67 increases at concentrations of denaturant that favor folding, indicating a compaction of the unfolded protein as observed previously in single-molecule Forster resonance energy transfer (FRET) experiments. JF - Journal of Molecular Biology AU - Buscaglia, M AU - Schuler, B AU - Lapidus, L J AU - Eaton, WA AU - Hofrichter, J AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Bethesda, MD 20892-0520, USA, eaton@helix.nih.gov Y1 - 2003/09/05/ PY - 2003 DA - 2003 Sep 05 SP - 9 EP - 12 VL - 332 IS - 1 SN - 0022-2836, 0022-2836 KW - Microbiology Abstracts B: Bacteriology KW - Tryptophan KW - Triplet state KW - Protein folding KW - Cysteine KW - Kinetics KW - fluorescence resonance energy transfer KW - Cold shock KW - Thermotoga maritima KW - Compaction KW - J 02330:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21286613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Kinetics+of+Intramolecular+Contact+Formation+in+a+Denatured+Protein&rft.au=Buscaglia%2C+M%3BSchuler%2C+B%3BLapidus%2C+L+J%3BEaton%2C+WA%3BHofrichter%2C+J&rft.aulast=Buscaglia&rft.aufirst=M&rft.date=2003-09-05&rft.volume=332&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1016%2FS0022-2836%2803%2900891-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Triplet state; Tryptophan; Protein folding; Cysteine; Kinetics; fluorescence resonance energy transfer; Cold shock; Compaction; Thermotoga maritima DO - http://dx.doi.org/10.1016/S0022-2836(03)00891-X ER - TY - JOUR T1 - Impact of genetic analysis on Parkinson's disease research. AN - 85378431; pmid-14502662 AB - Genetic analysis is changing our view of Parkinson's disease: not only is it challenging the long-cherished views about the diagnosis of the disease, it is also starting to suggest a biochemical pathway to disease pathogenesis. These developments are reviewed in the context of three known (synuclein, parkin, and DJ-1) and one suspected (ubiquitin hydrolase) genes for the disease.Copyright 2003 Movement Disorder Society JF - Movement disorders : official journal of the Movement Disorder Society AU - Hardy, John AD - Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. hardyj@mail.nih.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - S96 EP - S98 VL - 18 Suppl 6 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - *Cysteine Endopeptidases: genetics KW - DNA Mutational Analysis KW - Genetic Predisposition to Disease: genetics KW - Humans KW - Intracellular Signaling Peptides and Proteins KW - *Multienzyme Complexes: genetics KW - *Nerve Tissue Proteins: genetics KW - *Oncogene Proteins: genetics KW - Parkinson Disease: diagnosis KW - *Parkinson Disease: genetics KW - Proteasome Endopeptidase Complex KW - Synucleins KW - *Ubiquitin: genetics KW - *Ubiquitin-Protein Ligases: genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85378431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Impact+of+genetic+analysis+on+Parkinson%27s+disease+research.&rft.au=Hardy%2C+John&rft.aulast=Hardy&rft.aufirst=John&rft.date=2003-09-01&rft.volume=18+Suppl+6&rft.issue=&rft.spage=S96&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Dexamethasone suppresses peripheral prostanoid levels without analgesia in a clinical model of acute inflammation. AN - 85377134; pmid-12966473 AB - The therapeutic effects of glucocorticoids are generally attributed to suppression of multiple signaling pathways involved in the inflammatory response leading to decreased levels of inflammatory mediators at the site of injury. This study evaluated the in vivo relationship between levels of prostanoids at the site of tissue injury and analgesia after dexamethasone administration in a clinical model of tissue injury.Subjects were administered dexamethasone 4 mg or placebo 12 hours and 1 hour before the removal of 2 mandibular third molars. A microdialysis probe was implanted at each surgical site for measurement of immunoreactive prostaglandin E2 (PGE(2)) or immunoreactive thromboxane B(2) (TxB(2)), and pain was measured concurrently. Subjects received either ketorolac 30 mg intravenously or placebo at pain onset.PGE(2) was detectable in the first postoperative sample, decreased over the next hour and then increased coincident with the onset of postoperative pain. Administration of dexamethasone suppressed PGE(2) levels in samples collected at pain onset in comparison to placebo and significantly suppressed TxB(2) at the surgical site but without any effect on pain report. Subsequent administration of ketorolac significantly reduced pain while decreasing both PGE(2) and TxB(2) levels at the surgical site.The lack of an analgesic effect for dexamethasone while reducing both PGE(2) and TxB(2) at the site of injury in comparison to ketorolac analgesia accompanied by greater reductions in levels of these prostanoids suggests that glucocorticoids at this dose do not suppress PGE(2) release sufficiently to attenuate peripheral sensitization of nociceptors after tissue injury. JF - Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons AU - Dionne, Raymond A AU - Gordon, Sharon M AU - Rowan, Janet AU - Kent, Allison AU - Brahim, Jaime S AD - Pain and Naurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research/NIH, 10 Center Drive, Bethesda, MD 20892-2292, USA. rdionne@dir.nidcr.noh.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 997 EP - 1003 VL - 61 IS - 9 SN - 0278-2391, 0278-2391 KW - National Library of Medicine KW - Adult KW - Analgesia KW - Analysis of Variance KW - *Anti-Inflammatory Agents, Non-Steroidal: administration & dosage KW - *Dexamethasone: administration & dosage KW - *Dinoprostone: antagonists & inhibitors KW - Double-Blind Method KW - Female KW - Humans KW - *Ketorolac: administration & dosage KW - Male KW - Mandible KW - *Molar, Third: surgery KW - Pain Measurement KW - *Pain, Postoperative: drug therapy KW - Postoperative Care KW - Preoperative Care KW - Prospective Studies KW - *Thromboxane B2: antagonists & inhibitors KW - *Tooth Extraction KW - Tooth, Impacted: surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85377134?accountid=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+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.atitle=Dexamethasone+suppresses+peripheral+prostanoid+levels+without+analgesia+in+a+clinical+model+of+acute+inflammation.&rft.au=Dionne%2C+Raymond+A%3BGordon%2C+Sharon+M%3BRowan%2C+Janet%3BKent%2C+Allison%3BBrahim%2C+Jaime+S&rft.aulast=Dionne&rft.aufirst=Raymond&rft.date=2003-09-01&rft.volume=61&rft.issue=9&rft.spage=997&rft.isbn=&rft.btitle=&rft.title=Journal+of+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.issn=02782391&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Sensory training as treatment for focal hand dystonia: a 1-year follow-up. AN - 85376653; pmid-14502673 AB - In a prior study, 10 patients with focal hand dystonia learned braille reading as sensory training for 8 weeks. Practice time was 30 to 60 minutes daily. They improved both their spatial acuity using the Grating Orientation Discrimination Task (GOT) and their dystonia using the Fahn scale. Three patients continued training for 1 year. Patients showed further improvement in the GOT, writing a standard paragraph, and self-rating scales. Sensory training lasting longer than 8 weeks may lead to continued improvement.Copyright 2003 Movement Disorder Society JF - Movement disorders : official journal of the Movement Disorder Society AU - Zeuner, Kirsten E AU - Hallett, Mark AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 1044 EP - 1047 VL - 18 IS - 9 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Discrimination Learning KW - Dystonic Disorders: physiopathology KW - *Dystonic Disorders: rehabilitation KW - Female KW - Follow-Up Studies KW - *Hand: physiopathology KW - Humans KW - Middle Aged KW - *Psychomotor Performance KW - Sensory Thresholds KW - Treatment Outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85376653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Sensory+training+as+treatment+for+focal+hand+dystonia%3A+a+1-year+follow-up.&rft.au=Zeuner%2C+Kirsten+E%3BHallett%2C+Mark&rft.aulast=Zeuner&rft.aufirst=Kirsten&rft.date=2003-09-01&rft.volume=18&rft.issue=9&rft.spage=1044&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - A pilot study of dose intense doxorubicin and cyclophosphamide followed by infusional paclitaxel in high-risk primary breast cancer. AN - 75755125; 14531496 AB - We conducted a pilot study of dose dense doxorubicin and cyclophosphamide (AC) combination chemotherapy followed by infusional paclitaxel (T) in primary breast cancer to determine its safety and feasibility. Twenty-two subjects (10 with stage II and > or = 4 positive lymph nodes, and 12 with stage III disease) were treated with AC (A 60 mg/m2 and C 2000 mg/m2) with filgrastim every 14 days for three cycles followed by infusional paclitaxel (140 mg/m2 over 96 h) every 14 days for three cycles. Mean overall cycle length was 15.3 days and mean duration of therapy was 92 days. Dose reductions of C or T were required in 7/132 (5.3%) cycles for mucositis, diarrhea, or failure to recover platelets by day 15. Ninety-five percent of subjects had grade 4 neutropenia and 1 subject had a platelet nadir of < 20,000. Actual delivered dose intensity (DI) over six cycles was: A 27 mg/m2 per week; C 892 mg/m2 per week; T 64 mg/m2 per week (90.6, 89.2, and 91.4% of planned DI, respectively). Average total dose administered was: A 180 mg/m2; C 5880 mg/m2; T 403 mg/m2 (100, 98, and 96% of planned total doses, respectively). Clinical response rate in 10 subjects receiving neoadjuvant therapy was 100% (4 complete response, 6 partial response). Four subjects had a pathologic complete response (three subjects without evidence of malignancy and one subject with ductal carcinoma in situ.) Administration of dose dense AC followed by infusional paclitaxel in 14-day cycles is feasible and this regimen is active in breast cancer. JF - Breast cancer research and treatment AU - Zujewski, Jo Anne AU - Eng-Wong, Jennifer AU - O'Shaughnessy, Joyce AU - Venzon, David AU - Chow, Catherine AU - Danforth, David AU - Kohler, David R AU - Cusack, Georgia AU - Riseberg, David AU - Cowan, Kenneth H AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. zujewskj@mail.nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 41 EP - 51 VL - 81 IS - 1 SN - 0167-6806, 0167-6806 KW - Antibiotics, Antineoplastic KW - 0 KW - Antineoplastic Agents, Alkylating KW - Antineoplastic Agents, Phytogenic KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Cyclophosphamide -- administration & dosage KW - Drug Administration Schedule KW - Antibiotics, Antineoplastic -- administration & dosage KW - Humans KW - Treatment Outcome KW - Neutropenia -- chemically induced KW - Pilot Projects KW - Doxorubicin -- administration & dosage KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Female KW - Chemotherapy, Adjuvant KW - Breast Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75755125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=A+pilot+study+of+dose+intense+doxorubicin+and+cyclophosphamide+followed+by+infusional+paclitaxel+in+high-risk+primary+breast+cancer.&rft.au=Zujewski%2C+Jo+Anne%3BEng-Wong%2C+Jennifer%3BO%27Shaughnessy%2C+Joyce%3BVenzon%2C+David%3BChow%2C+Catherine%3BDanforth%2C+David%3BKohler%2C+David+R%3BCusack%2C+Georgia%3BRiseberg%2C+David%3BCowan%2C+Kenneth+H&rft.aulast=Zujewski&rft.aufirst=Jo&rft.date=2003-09-01&rft.volume=81&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=01676806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-20 N1 - Date created - 2003-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retroviral insertional mutagenesis identifies a small protein required for synthesis of diphthamide, the target of bacterial ADP-ribosylating toxins. AN - 75743130; 14527407 AB - Retroviral insertional mutagenesis was used to produce a mutant Chinese hamster ovary cell line that is completely resistant to several different bacterial ADP-ribosylating toxins. The gene responsible for toxin resistance, termed diphtheria toxin (DT) and Pseudomonas exotoxin A (ETA) sensitivity required gene 1 (DESR1), encodes two small protein isoforms of 82 and 57 residues. DESR1 is evolutionally conserved and ubiquitously expressed. Only the longer isoform is functional because the mutant cell line can be complemented by transfection with the long but not the short isoform. We demonstrate that DESR1 is required for the first step in the posttranslational modification of elongation factor-2 at His(715) that yields diphthamide, the target site for ADP ribosylation by DT and ETA. KTI11, the analog of DESR1 in yeast, which was originally identified as a gene regulating the sensitivity of yeast to zymocin, is also required for diphthamide biosynthesis, implicating DESR1/KTI11 in multiple biological processes. JF - Molecular cell AU - Liu, Shihui AU - Leppla, Stephen H AD - Microbial Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 603 EP - 613 VL - 12 IS - 3 SN - 1097-2765, 1097-2765 KW - Bacterial Toxins KW - 0 KW - KTI11 protein, S cerevisiae KW - Peptide Elongation Factor 2 KW - Protein Isoforms KW - Repressor Proteins KW - Saccharomyces cerevisiae Proteins KW - Histidine KW - 4QD397987E KW - diphthamide KW - 75645-22-6 KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Index Medicus KW - Animals KW - Peptide Elongation Factor 2 -- metabolism KW - Sequence Homology, Nucleic Acid KW - Protein Processing, Post-Translational KW - Peptide Elongation Factor 2 -- genetics KW - Immunity, Innate -- genetics KW - Eukaryotic Cells -- microbiology KW - Molecular Weight KW - Eukaryotic Cells -- metabolism KW - Protein Isoforms -- isolation & purification KW - ADP-Ribosylation Factors -- metabolism KW - Molecular Sequence Data KW - CHO Cells KW - Mutation -- genetics KW - Sequence Homology, Amino Acid KW - Retroviridae -- genetics KW - Protein Isoforms -- genetics KW - Cricetinae KW - Repressor Proteins -- isolation & purification KW - Bacterial Toxins -- metabolism KW - Saccharomyces cerevisiae Proteins -- genetics KW - Histidine -- biosynthesis KW - Bacterial Infections -- immunology KW - Histidine -- analogs & derivatives KW - Repressor Proteins -- genetics KW - Mutagenesis, Insertional KW - Histidine -- metabolism KW - Saccharomyces cerevisiae Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75743130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Retroviral+insertional+mutagenesis+identifies+a+small+protein+required+for+synthesis+of+diphthamide%2C+the+target+of+bacterial+ADP-ribosylating+toxins.&rft.au=Liu%2C+Shihui%3BLeppla%2C+Stephen+H&rft.aulast=Liu&rft.aufirst=Shihui&rft.date=2003-09-01&rft.volume=12&rft.issue=3&rft.spage=603&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 - 2003-11-06 N1 - Date created - 2003-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decreased frequency and highly aberrant spectrum of ultraviolet-induced mutations in the hprt gene of mouse fibroblasts expressing antisense RNA to DNA polymerase zeta. AN - 75737681; 14517346 AB - In the budding yeast Saccharomyces cerevisiae, DNA polymerase zeta (pol zeta) is responsible for the great majority of mutations generated during error-prone translesion replication of DNA that contains UV-induced lesions. The catalytic subunit of pol zeta is encoded by the Rev3 gene. The orthologue of Rev3 has been cloned from higher eukaryotic cells, including human, but its role in mutagenesis and carcinogenesis remains obscure. Investigation into the cellular function of pol zeta has been hindered by the fact that Rev3 knockout mice do not survive beyond midgestation, and embryonic stem cells used to derive these mice are not genetically stable. We have generated a transgenic mouse that expresses antisense RNA transcripts to mRev3 endogeneous RNA. These mice are viable, have greatly reduced levels of Rev3 transcript, and have reduced levels of B cells and impaired development of high-affinity memory B cells. Here, we report that exposure of fibroblasts derived from these mice to UV resulted in a 4-5-fold reduction in mutant frequency at the hprt locus at every dose examined, and the mutation spectrum was highly aberrant compared with the control cells. In the control cells, 80% of the mutations were transitions and approximately 75% of these arose from photoproducts in the putative leading strand template. Strikingly, in transgenic cells, most of the mutations were transversions and there was a complete loss of strand bias. This mutation spectrum is highly aberrant and is similar to that induced by UV in human xeroderma pigmentosum variant cells, which lack polymerase eta. These data indicate that most UV-induced mutations are dependent on DNA pol zeta, a function that has been conserved from yeast to higher eukaryotic cells. However, in mammalian cells, other DNA polymerase(s) may accomplish error-prone translesion replication and are responsible for residual UV mutagenesis observed in the absence of pol zeta. Further, these data support a central role for DNA polymerase eta in the error-free bypass of UV photoproducts. The antisense Rev3 mice should be a useful model to study mutagenic lesion bypass by pol zeta in mammalian cells and to investigate the role this polymerase plays in carcinogenesis. JF - Molecular cancer research : MCR AU - Diaz, Marilyn AU - Watson, Nicholas B AU - Turkington, Gene AU - Verkoczy, Laurent K AU - Klinman, Norman R AU - McGregor, William Glenn AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 836 EP - 847 VL - 1 IS - 11 SN - 1541-7786, 1541-7786 KW - RNA, Antisense KW - 0 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - DNA polymerase zeta KW - EC 2.7.7.- KW - Rev3 protein, mouse KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Animals KW - Cells, Cultured KW - Humans KW - Transgenes KW - Mutation -- genetics KW - Mice KW - Cell Survival -- radiation effects KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Transgenic KW - Cell Cycle -- radiation effects KW - Fibroblasts KW - DNA Damage -- drug effects KW - Mutagenesis -- radiation effects KW - Ultraviolet Rays KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - RNA, Antisense -- genetics KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75737681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cancer+research+%3A+MCR&rft.atitle=Decreased+frequency+and+highly+aberrant+spectrum+of+ultraviolet-induced+mutations+in+the+hprt+gene+of+mouse+fibroblasts+expressing+antisense+RNA+to+DNA+polymerase+zeta.&rft.au=Diaz%2C+Marilyn%3BWatson%2C+Nicholas+B%3BTurkington%2C+Gene%3BVerkoczy%2C+Laurent+K%3BKlinman%2C+Norman+R%3BMcGregor%2C+William+Glenn&rft.aulast=Diaz&rft.aufirst=Marilyn&rft.date=2003-09-01&rft.volume=1&rft.issue=11&rft.spage=836&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+research+%3A+MCR&rft.issn=15417786&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-14 N1 - Date created - 2003-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment-seeking inpatient cocaine abusers show hypothalamic dysregulation of both basal prolactin and cortisol secretion. AN - 75714348; 14512708 AB - Cocaine causes neuroendocrine aberrations in cocaine abusers with pituitary stress hormone secretion providing a window to the stress system in the brain. Substance abusers and control participants were hormonally profiled for 3 weeks. Abusers showed significant basal elevations in prolactin in week 1 with normalization over the 3 weeks. No differences in prolactin secretion were seen with either thyrotropin-releasing hormone stimulation or L-dopa suppression testing. Basal afternoon cortisol secretion was significantly elevated during weeks 1 and 2 comparing abusers to controls. Elevated afternoon cortisol secretion is a sensitive indicator of central stress activation. These results point to the hypothalamus, not the pituitary gland, as being primarily altered in cocaine withdrawal. The data demonstrate that both the dopamine-prolactin and hypothalamic-pituitary-adrenal (HPA) axes are affected during cocaine cessation. As medications are developed to modulate activation of a dysfunctional stress system, future therapeutic studies of substance abuse, withdrawal, craving and relapse should employ more sophisticated tests of hypothalamic pituitary function, especially the HPA axis, as this information may be a guide in the diagnosis and predict clinical responses. Copyright 2003 S. Karger AG, Basel JF - Neuroendocrinology AU - Contoreggi, Carlo AU - Herning, Ronald I AU - Koeppl, Bonnie AU - Simpson, Pippa M AU - Negro, Paulo J AU - Fortner-Burton, Carolyn AU - Hess, Judith AD - Intramural Research Program, National Institute on Drug Abuse, PO Box 5180, Baltimore, MD 21224, USA. ccontore@intra.nida.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 154 EP - 162 VL - 78 IS - 3 SN - 0028-3835, 0028-3835 KW - Prolactin KW - 9002-62-4 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Reference Values KW - Analysis of Variance KW - Substance Abuse Treatment Centers KW - Area Under Curve KW - Humans KW - Adult KW - Inpatients KW - Personality Assessment KW - Time Factors KW - Prolactin -- blood KW - Prolactin -- secretion KW - Hypothalamo-Hypophyseal System -- physiopathology KW - Pituitary-Adrenal System -- physiopathology KW - Hydrocortisone -- secretion KW - Cocaine-Related Disorders -- physiopathology KW - Cocaine-Related Disorders -- therapy KW - Hydrocortisone -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75714348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Treatment-seeking+inpatient+cocaine+abusers+show+hypothalamic+dysregulation+of+both+basal+prolactin+and+cortisol+secretion.&rft.au=Contoreggi%2C+Carlo%3BHerning%2C+Ronald+I%3BKoeppl%2C+Bonnie%3BSimpson%2C+Pippa+M%3BNegro%2C+Paulo+J%3BFortner-Burton%2C+Carolyn%3BHess%2C+Judith&rft.aulast=Contoreggi&rft.aufirst=Carlo&rft.date=2003-09-01&rft.volume=78&rft.issue=3&rft.spage=154&rft.isbn=&rft.btitle=&rft.title=Neuroendocrinology&rft.issn=00283835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-18 N1 - Date created - 2003-09-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dexamethasone and medroxyprogesterone acetate elevate Nm23-H1 metastasis suppressor gene expression in metastatic human breast carcinoma cells: new uses for old compounds. AN - 75703961; 14506169 AB - Long-term elevation of metastasis suppressor gene expression in micrometastases represents a novel therapeutic strategy for breast and other cancers. We searched for well-tolerated compounds that could elevate Nm23 metastasis suppressor expression in metastatic human breast cancer cell lines. MDA-MB-435 and MDA-MB-231 human breast carcinoma cells were treated with dexamethasone or medroxyprogesterone acetate (MPA) in cultures containing either charcoal-stripped serum or FCS. Aspects of nm23 expression and function were determined. Previous investigation of the nm23-H1 promoter suggested that glucocorticoids may contribute to the elevation of Nm23-H1 expression. Dexamethasone elevated Nm23-H1 and Nm23-H2 protein levels in two metastatic human breast carcinoma cell lines 2-3-fold over a 4-day time course when cultured in steroid-free culture medium, with high-dose inhibition, via a traditional transcriptional mechanism. Elevation of Nm23-H1 expression was not observed using FCS-containing culture medium, which contains endogenous levels of corticosteroids, limiting the potential in vivo use of dexamethasone. MPA was investigated as a glucocorticoid receptor agonist. MPA elevated breast carcinoma Nm23-H1 protein expression 3-fold over a 10 nM to 1 micro M dose range when cultured in steroid-free or FCS-containing medium, with a shorter time course. Elevation of Nm23-H1 expression in the presence of endogenous corticosteroids found in FCS involved a distinct, glucocorticoid receptor-dependent, posttranscriptional mechanism of action. MPA had no effect on proliferation in vitro but reduced the soft agar colonization of metastatic breast cancer cell lines by approximately 50%. MPA represents a first generation lead agent for the elevation of Nm23-H1 metastasis suppressor expression and the inhibition of metastatic colonization. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Ouatas, Taoufik AU - Halverson, Douglas AU - Steeg, Patricia S AD - Women's Cancers Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 3763 EP - 3772 VL - 9 IS - 10 Pt 1 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Contraceptives, Oral, Synthetic KW - Glucocorticoids KW - NM23 Nucleoside Diphosphate Kinases KW - Dexamethasone KW - 7S5I7G3JQL KW - Agar KW - 9002-18-0 KW - Medroxyprogesterone Acetate KW - C2QI4IOI2G KW - NME1 protein, human KW - EC 2.7.4.6 KW - Nucleoside-Diphosphate Kinase KW - Medroxyprogesterone KW - HSU1C9YRES KW - Index Medicus KW - Glucocorticoids -- metabolism KW - Medroxyprogesterone Acetate -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Antineoplastic Agents, Hormonal -- pharmacology KW - Contraceptives, Oral, Synthetic -- pharmacology KW - Transcription, Genetic KW - Cell Line, Tumor KW - RNA Processing, Post-Transcriptional KW - Mutagenesis KW - Promoter Regions, Genetic KW - Blotting, Western KW - Agar -- chemistry KW - Transfection KW - Neoplasm Metastasis KW - Time Factors KW - Cell Division KW - Gene Expression Regulation, Neoplastic KW - Breast Neoplasms -- drug therapy KW - Protein Biosynthesis KW - Dexamethasone -- metabolism KW - Dexamethasone -- pharmacology KW - Medroxyprogesterone -- pharmacology KW - Breast Neoplasms -- therapy KW - Breast Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75703961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dexamethasone+and+medroxyprogesterone+acetate+elevate+Nm23-H1+metastasis+suppressor+gene+expression+in+metastatic+human+breast+carcinoma+cells%3A+new+uses+for+old+compounds.&rft.au=Ouatas%2C+Taoufik%3BHalverson%2C+Douglas%3BSteeg%2C+Patricia+S&rft.aulast=Ouatas&rft.aufirst=Taoufik&rft.date=2003-09-01&rft.volume=9&rft.issue=10+Pt+1&rft.spage=3763&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 - 2004-05-28 N1 - Date created - 2003-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Forestomach tumor induction by 2,4-hexadienal in F344N rats and B6C3F1 mice. AN - 75702740; 12879212 AB - 2,4-Hexadienal (2,4-Hx) was studied for its toxicity and carcinogenicity because of its alpha, beta-unsaturated aldehyde structure and potential link between exposure to lipid peroxidation products in the diet and human malignancies. Male and female F344N rats and B6C3F1 mice received 2,4-Hx in corn oil by gavage for 16 days, 14 weeks, or 2 years. In the 16-day studies 2,4-Hx induced forestomach necrosis and ulceration at 240 mg/kg and forestomach epithelial hyperplasia at 80 mg/kg in rats and mice. In the 14-week studies the chemical induced forestomach hyperplasia and nasal olfactory atrophy or necrosis at 120 mg/kg in rats and mice. In the 2-year studies 2,4-Hx induced squamous cell papilloma and carcinoma of the forestomach in male and female rats at 45 and 90 mg/kg and in male and female mice at 120 mg/kg. Two male mice in the 120 mg/kg group had uncommon squamous cell carcinoma of the oral cavity (tongue). Mechanistic studies indicated that the forestomach carcinogenesis in rats and mice may be due to depletion of glutathione as a result of oxidative stress induced by 2,4-Hx. JF - Archives of toxicology AU - Chan, Po C AU - Mahler, Joel AU - Peddada, Shyamal AU - Lomnitski, Liat AU - Nyska, Abraham AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. chanp@niehs.nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 511 EP - 520 VL - 77 IS - 9 SN - 0340-5761, 0340-5761 KW - Aldehydes KW - 0 KW - Alkadienes KW - Carcinogens KW - Food Additives KW - 2,4-hexadienal KW - 80466-34-8 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Neoplasms, Squamous Cell -- pathology KW - Administration, Oral KW - Animals KW - Liver -- pathology KW - Papilloma -- pathology KW - Glutathione -- metabolism KW - Mice KW - Rats KW - Neoplasms, Squamous Cell -- chemically induced KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Hyperplasia KW - Oxidative Stress KW - Body Weight -- drug effects KW - Carcinogenicity Tests KW - Papilloma -- chemically induced KW - Female KW - Male KW - Organ Size -- drug effects KW - Aldehydes -- toxicity KW - Stomach Neoplasms -- pathology KW - Stomach -- pathology KW - Stomach Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Alkadienes -- toxicity KW - Food Additives -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75702740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+toxicology&rft.atitle=Forestomach+tumor+induction+by+2%2C4-hexadienal+in+F344N+rats+and+B6C3F1+mice.&rft.au=Chan%2C+Po+C%3BMahler%2C+Joel%3BPeddada%2C+Shyamal%3BLomnitski%2C+Liat%3BNyska%2C+Abraham&rft.aulast=Chan&rft.aufirst=Po&rft.date=2003-09-01&rft.volume=77&rft.issue=9&rft.spage=511&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology&rft.issn=03405761&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-30 N1 - Date created - 2003-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced cell killing induced by the combination of radiation and the heat shock protein 90 inhibitor 17-allylamino-17- demethoxygeldanamycin: a multitarget approach to radiosensitization. AN - 75698991; 14506167 AB - Current strategies for tumor cell radiosensitization focus on a target-based approach. However, the radioresponse of a tumor cell is influenced by a wide variety of signaling molecules existing in a number of different survival pathways. Therefore, in an attempt to increase the probability and/or degree of radiosensitization, we have begun to investigate a multitarget approach using the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17AAG). The effect of 17AAG on the levels of three proteins (Raf-1, ErbB2, and Akt) previously implicated in the regulation of radiosensitivity was determined in four human tumor cell lines. Tumor cell survival after exposure to corresponding concentrations of 17AAG combined with clinically relevant doses of X-rays was then evaluated using a clonogenic assay. The radiosensitivity of a nonimmortalized, normal fibroblast cell line was also determined after exposure to 17AAG. Exposure to nanomolar concentrations of 17AAG reduced the levels of the three radiosensitivity-associated proteins in a cell type manner. Using corresponding concentrations, 17AAG enhanced the radiosensitivity of each of the tumor cell lines with enhancement factors ranging from 1.3 to 1.7. The enhancement appeared to be related to the number of radioresponse-regulatory proteins affected. In contrast to the tumor cell lines, 17AAG had no effect on the radiosensitivity of a normal, nonimmortalized human fibroblast cell line. These data suggest that heat shock protein 90 may be an appropriate target for selectively enhancing the radiosensitivity of tumor cells over normal cells. Furthermore, they illustrate the potential of a multitarget approach to radiosensitization. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Russell, Jeffery S AU - Burgan, William AU - Oswald, Kelli A AU - Camphausen, Kevin AU - Tofilon, Philip J AD - Molecular Radiation Therapeutics Branch, Radiation Oncology Science Program, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 3749 EP - 3755 VL - 9 IS - 10 Pt 1 SN - 1078-0432, 1078-0432 KW - Benzoquinones KW - 0 KW - HSP90 Heat-Shock Proteins KW - Lactams, Macrocyclic KW - Radiation-Sensitizing Agents KW - Rifabutin KW - 1W306TDA6S KW - tanespimycin KW - 4GY0AVT3L4 KW - Index Medicus KW - Immunoblotting KW - Combined Modality Therapy KW - Dose-Response Relationship, Drug KW - Humans KW - Radiation Tolerance KW - Cell Line, Tumor KW - Dose-Response Relationship, Radiation KW - Fibroblasts -- metabolism KW - Cell Survival KW - Cell Death KW - Time Factors KW - Cell Cycle KW - Cell Line KW - Rifabutin -- analogs & derivatives KW - Radiation-Sensitizing Agents -- pharmacology KW - Radiotherapy -- methods KW - HSP90 Heat-Shock Proteins -- antagonists & inhibitors KW - Rifabutin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75698991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Enhanced+cell+killing+induced+by+the+combination+of+radiation+and+the+heat+shock+protein+90+inhibitor+17-allylamino-17-+demethoxygeldanamycin%3A+a+multitarget+approach+to+radiosensitization.&rft.au=Russell%2C+Jeffery+S%3BBurgan%2C+William%3BOswald%2C+Kelli+A%3BCamphausen%2C+Kevin%3BTofilon%2C+Philip+J&rft.aulast=Russell&rft.aufirst=Jeffery&rft.date=2003-09-01&rft.volume=9&rft.issue=10+Pt+1&rft.spage=3749&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 - 2004-05-28 N1 - Date created - 2003-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - STAT-3 activity in chemically-induced hepatocellular carcinoma. AN - 73719985; 12957465 AB - The signal transducer and activator of transcription (STAT)-3 regulates basic biological processes and it has been reported to be constitutively active in different types of malignant tumours. STAT-3 is active during the regenerative growth of the liver, but there are hardly any data about its presence in liver tumours. We investigated and found a high activity of STAT-3 using an electrophoretic mobility shift assay (EMSA) in chemically-induced rat hepatocellular carcinomas (HCCs). Dexamethasone treatment downregulated both STAT-3 activity and cell proliferation in the tumours. Therefore, the activity of the STAT-3 signal transduction pathway seems to be required for the growth of HCCs and could be a potential new target for therapeutic trials of this tumour type. JF - European journal of cancer (Oxford, England : 1990) AU - Sánchez, A AU - Nagy, P AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, MD, Bethesda, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 2093 EP - 2098 VL - 39 IS - 14 SN - 0959-8049, 0959-8049 KW - Alkylating Agents KW - 0 KW - Antineoplastic Agents, Hormonal KW - Carcinogens KW - DNA-Binding Proteins KW - Interleukin-6 KW - STAT3 Transcription Factor KW - Stat3 protein, rat KW - Trans-Activators KW - Tumor Necrosis Factor-alpha KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - RNA KW - 63231-63-0 KW - Dexamethasone KW - 7S5I7G3JQL KW - 2-Acetylaminofluorene KW - 9M98QLJ2DL KW - Index Medicus KW - Animals KW - Blotting, Northern KW - Dexamethasone -- therapeutic use KW - Electrophoretic Mobility Shift Assay KW - Interleukin-6 -- metabolism KW - Rats KW - 2-Acetylaminofluorene -- adverse effects KW - Diethylnitrosamine -- adverse effects KW - RNA -- metabolism KW - Tumor Necrosis Factor-alpha -- metabolism KW - Alkylating Agents -- adverse effects KW - Antineoplastic Agents, Hormonal -- therapeutic use KW - Male KW - Carcinogens -- adverse effects KW - Trans-Activators -- metabolism KW - Liver Neoplasms -- metabolism KW - Carcinoma, Hepatocellular -- metabolism KW - Liver Neoplasms -- chemically induced KW - Carcinoma, Hepatocellular -- chemically induced KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73719985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=STAT-3+activity+in+chemically-induced+hepatocellular+carcinoma.&rft.au=S%C3%A1nchez%2C+A%3BNagy%2C+P%3BThorgeirsson%2C+S+S&rft.aulast=S%C3%A1nchez&rft.aufirst=A&rft.date=2003-09-01&rft.volume=39&rft.issue=14&rft.spage=2093&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-23 N1 - Date created - 2003-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional genomics as a window on radiation stress signaling. AN - 73695746; 12947389 AB - Exposure to ionizing radiation, as well as other stresses, results in the activation of complex signal transduction pathways, which eventually shape the response of cells and organisms. Some of the important pathways responding to radiation include the ATM/P53 pathway, MAPK cascades and NF-kappaB activation, as well as signaling events initiated at the cell membrane and within the cytoplasm. Alterations in gene expression play roles both as intermediaries in signaling and as downstream effector genes. Differences in cell type, interindividual genetic differences and crosstalk occurring between signaling pathways may help to channel radiation stress signals between cell cycle delay, enhanced DNA repair, and apoptosis. These differences may in turn help determine the likelihood of late effects of radiation exposure, including carcinogenesis and fibrosis. The tools of the postgenomic era enable high-throughput studies of the multiple changes resulting from the interplay of radiation signaling pathways. Gene expression profiling, in particular shows great promise, both in terms of insight into basic molecular mechanisms and for the future hope of biomarker development and individual tailoring of cancer therapy. JF - Oncogene AU - Amundson, Sally A AU - Bittner, Michael AU - Fornace, Albert J AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. amundson@mail.nih.gov Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 5828 EP - 5833 VL - 22 IS - 37 SN - 0950-9232, 0950-9232 KW - Index Medicus KW - Space life sciences KW - Animals KW - Humans KW - Signal Transduction -- physiology KW - Signal Transduction -- radiation effects KW - Genomics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73695746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+genomics+as+a+window+on+radiation+stress+signaling.&rft.au=Amundson%2C+Sally+A%3BBittner%2C+Michael%3BFornace%2C+Albert+J&rft.aulast=Amundson&rft.aufirst=Sally&rft.date=2003-09-01&rft.volume=22&rft.issue=37&rft.spage=5828&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-01 N1 - Date created - 2003-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell transfer therapy for cancer: lessons from sequential treatments of a patient with metastatic melanoma. AN - 73667981; 12973027 AB - The development of effective autologous cell transfer therapies for the treatment of patients with cancer has been difficult, in part because the cells used to treat each patient are different, as are the patient's tumor and immune status. Much can thus be learned by sequential treatments of the same patient with the same cells, making single modifications in the treatments to determine which factors are critical. The authors have treated a single patient with five sequential administrations of the same cells with minor modifications in the mode of administration and the immune status of the patient. The treatment of this patient strongly suggested that 1) the highly avid recognition of tumor antigens in vitro by a transferred lymphocyte population does not necessarily predict in vivo antitumor activity; 2) the administration of highly avid antitumor autologous lymphocyte populations can be far more active in mediating tumor regression in vivo when administered after nonmyeloablative chemotherapy than when administered without this prior chemotherapy; 3) intra-arterial administration of highly avid antitumor autologous lymphocytes into the blood supply of the tumor can be more effective in mediating tumor regression than the intravenous administration of these same tumor infiltrating lymphocytes; 4) one mechanism of tumor escape from immunotherapy is loss of class I MHC antigen expression by the tumor due to mutation of the beta-2 microglobulin gene. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Rosenberg, Steven A AU - Yang, James C AU - Robbins, Paul F AU - Wunderlich, John R AU - Hwu, Patrick AU - Sherry, Richard M AU - Schwartzentruber, Douglas J AU - Topalian, Suzanne L AU - Restifo, Nicholas P AU - Filie, Armando AU - Chang, Richard AU - Dudley, Mark E AD - Center for Cancer Research, Surgery Branch, National Cancer Institute, National Institute of Health, Building 10, Room 2B42, 10 Center Drive, Bethesda, Maryland 20892, USA. sar@nih.gov PY - 2003 SP - 385 EP - 393 VL - 26 IS - 5 SN - 1524-9557, 1524-9557 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Neoplasm KW - HLA-A2 Antigen KW - Interleukin-2 KW - beta 2-Microglobulin KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Interleukin-2 -- administration & dosage KW - Combined Modality Therapy KW - Humans KW - CD8-Positive T-Lymphocytes -- transplantation KW - beta 2-Microglobulin -- genetics KW - HLA-A2 Antigen -- immunology KW - Tumor Cells, Cultured KW - Lymphocyte Transfusion KW - CD8-Positive T-Lymphocytes -- immunology KW - Cells, Cultured KW - Adult KW - Treatment Outcome KW - Antigens, Neoplasm -- immunology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Female KW - Lymphocytes -- immunology KW - Lymphocytes, Tumor-Infiltrating -- immunology KW - Skin Neoplasms -- immunology KW - Melanoma -- secondary KW - Immunotherapy, Adoptive KW - Skin Neoplasms -- therapy KW - Melanoma -- therapy KW - Melanoma -- immunology KW - Skin Neoplasms -- blood KW - Lymphocytes, Tumor-Infiltrating -- transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73667981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=Cell+transfer+therapy+for+cancer%3A+lessons+from+sequential+treatments+of+a+patient+with+metastatic+melanoma.&rft.au=Rosenberg%2C+Steven+A%3BYang%2C+James+C%3BRobbins%2C+Paul+F%3BWunderlich%2C+John+R%3BHwu%2C+Patrick%3BSherry%2C+Richard+M%3BSchwartzentruber%2C+Douglas+J%3BTopalian%2C+Suzanne+L%3BRestifo%2C+Nicholas+P%3BFilie%2C+Armando%3BChang%2C+Richard%3BDudley%2C+Mark+E&rft.aulast=Rosenberg&rft.aufirst=Steven&rft.date=2003-09-01&rft.volume=26&rft.issue=5&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-09 N1 - Date created - 2003-09-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: JAMA. 1994 Mar 23-30;271(12):907-13 [8120958] Invest New Drugs. 1991 Feb;9(1):105-8 [1709151] J Immunol Methods. 1990 Apr 17;128(2):189-201 [1691237] Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16168-73 [12427970] Nat Immunol. 2002 Nov;3(11):999-1005 [12407407] Cancer. 1994 Mar 15;73(6):1731-7 [8156501] J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66 [8028037] N Engl J Med. 1995 Oct 19;333(16):1038-44 [7675046] J Natl Cancer Inst. 1996 Jan 17;88(2):100-8 [8537970] Nat Med. 1998 Mar;4(3):321-7 [9500606] Science. 2002 Oct 25;298(5594):850-4 [12242449] J Immunother. 2002 May-Jun;25(3):243-51 [12000866] J Immunother. 2001 Jul-Aug;24(4):363-73 [11565838] Cancer J. 2000 Mar-Apr;6(2):69-77 [11069222] N Engl J Med. 2000 Sep 14;343(11):750-8 [10984562] J Immunother. 2000 May-Jun;23(3):387-92 [10838668] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutant thyroid hormone receptor beta represses the expression and transcriptional activity of peroxisome proliferator-activated receptor gamma during thyroid carcinogenesis. AN - 73667644; 14500358 AB - The molecular genetics underlying thyroid carcinogenesis is not clear. Recent identification of a PAX8-peroxisome proliferator-activated receptor gamma (PPARgamma) fusion gene in human thyroid follicular carcinoma suggests a tumor suppressor role of PPARgamma in thyroid carcinogenesis. Mice harboring a knockin mutant thyroid hormone beta receptor (TRbetaPV) spontaneously develop thyroid follicular carcinoma through pathological progression of hyperplasia, capsular invasion, vascular invasion, anaplasia, and eventually, distant organ metastasis. This mutant mouse (TRbeta(PV/PV) mouse) provides an unusual opportunity to ascertain the role of PPARgamma in thyroid carcinogenesis. Here, we show that the expression of PPARgamma mRNA was repressed in the thyroid gland of mutant mice during carcinogenesis. In addition, TRbetaPV acted to abolish the ligand (troglitazone)-mediated transcriptional activity of PPARgamma. These results indicate that repression of PPARgamma expression and its transcriptional activity are associated with thyroid carcinogenesis and raise the possibility that PPARgamma could be tested as a therapeutic target in thyroid follicular carcinoma. JF - Cancer research AU - Ying, Hao AU - Suzuki, Hideyo AU - Zhao, Li AU - Willingham, Mark C AU - Meltzer, Paul AU - Cheng, Sheue-Yann AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-4264, USA. Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 5274 EP - 5280 VL - 63 IS - 17 SN - 0008-5472, 0008-5472 KW - RNA, Messenger KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Thyroid Hormone KW - Thyroid Hormone Receptors beta KW - Transcription Factors KW - Lipoprotein Lipase KW - EC 3.1.1.34 KW - Index Medicus KW - Lipoprotein Lipase -- biosynthesis KW - Animals KW - Transfection KW - Lipoprotein Lipase -- genetics KW - Mice KW - RNA, Messenger -- genetics KW - Mutation KW - Immunohistochemistry KW - Transcriptional Activation KW - RNA, Messenger -- biosynthesis KW - Receptors, Cytoplasmic and Nuclear -- antagonists & inhibitors KW - Receptors, Thyroid Hormone -- biosynthesis KW - Transcription Factors -- antagonists & inhibitors KW - Thyroid Neoplasms -- genetics KW - Adenocarcinoma, Follicular -- metabolism KW - Thyroid Neoplasms -- metabolism KW - Adenocarcinoma, Follicular -- genetics KW - Receptors, Thyroid Hormone -- genetics KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Receptors, Cytoplasmic and Nuclear -- biosynthesis KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73667644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutant+thyroid+hormone+receptor+beta+represses+the+expression+and+transcriptional+activity+of+peroxisome+proliferator-activated+receptor+gamma+during+thyroid+carcinogenesis.&rft.au=Ying%2C+Hao%3BSuzuki%2C+Hideyo%3BZhao%2C+Li%3BWillingham%2C+Mark+C%3BMeltzer%2C+Paul%3BCheng%2C+Sheue-Yann&rft.aulast=Ying&rft.aufirst=Hao&rft.date=2003-09-01&rft.volume=63&rft.issue=17&rft.spage=5274&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 - 2003-11-06 N1 - Date created - 2003-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor-beta signaling in normal and malignant hematopoiesis. AN - 73652362; 12970772 AB - Transforming growth factor-beta (TGF-beta) is perhaps the most potent endogenous negative regulator of hematopoiesis. The intracellular signaling events mediating the effects of TGF-beta are multiple, involving extensive crosstalk between Smad-dependent and MAP-kinase-dependent pathways. We are only beginning to understand the importance of the balance between these cascades as a determinant of the response to TGF-beta, and have yet to determine the roles that disruption in TGF-beta signaling pathways might play in leukemogenesis. This review summarizes current knowledge regarding the function of TGF-beta in normal and malignant hematopoiesis. The principal observations made by gene targeting studies in mice are reviewed, with an emphasis on how a disruption of this pathway in vivo can affect blood cell development and immune homeostasis. We overview genetic alterations that lead to impaired TGF-beta signaling in hematopoietic neoplasms, including the suppression of Smad-dependent transcriptional responses by oncoproteins such as Tax and Evi-1, and fusion proteins such as AML1/ETO. We also consider mutations in genes encoding components of the core cell cycle machinery, such as p27(Kip1) and p15(INK4A), and emphasize their impact on the ability of TGF-beta to induce G1 arrest. The implications of these observations are discussed, and opinions regarding important directions for future research on TGF-beta in hematopoiesis are provided. JF - Leukemia AU - Kim, S-J AU - Letterio, J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1731 EP - 1737 VL - 17 IS - 9 SN - 0887-6924, 0887-6924 KW - Trans-Activators KW - 0 KW - Transforming Growth Factor beta KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Humans KW - Mice KW - Hematopoiesis -- physiology KW - Signal Transduction -- physiology KW - Transforming Growth Factor beta -- physiology KW - Leukemia -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73652362?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Transforming+growth+factor-beta+signaling+in+normal+and+malignant+hematopoiesis.&rft.au=Kim%2C+S-J%3BLetterio%2C+J&rft.aulast=Kim&rft.aufirst=S-J&rft.date=2003-09-01&rft.volume=17&rft.issue=9&rft.spage=1731&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-21 N1 - Date created - 2003-09-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of endogenous heme synthesis and degradation domain cysteines in cellular iron-dependent degradation of IRP2. AN - 73648157; 12972033 AB - Iron regulatory protein 2 (IRP2) is a mammalian cytosolic iron-sensing protein that regulates expression of iron metabolism proteins, including ferritin and transferrin receptor 1. IRP2 is ubiquitinated and degraded by the proteasome in iron-replete cells but is relatively stable in iron-depleted cells. Recent work has shown that IRP2 contains a unique 73-amino-acid domain that binds iron in vitro and undergoes iron-dependent oxidation and cleavage (J. Biol. Chem. 278 (2003), 14857). Several cysteines in the 73-amino-acid domain function as an in vitro iron-binding site. To assess the role of these cysteines in cellular iron- dependent degradation of IRP2, we mutagenized these cysteines in various combinations in the context of full-length protein and generated cell lines in which recombinant IRP2 expression was inducible. Iron-dependent degradation of IRP2 mutagenized at any or all of the cysteines of the putative degradation domain in cells was comparable to wild-type (WT). Both WT and cysteine mutant protein were stabilized in 3% oxygen. Treatment with sodium nitroprusside (SNP), an NO+ donor, caused a decrease in cellular IRP2 concentrations, but the SNP effect was abrogated by simultaneous addition of the iron chelator desferal and was not affected by cysteine mutations. Inhibition of endogenous heme synthesis with succinylacetone significantly inhibited iron- dependent degradation of IRP2. Addition of cobalt chloride inhibited degradation of both WT and mutagenized IRP2. Thus, we could not discern a role for the recently defined in vitro cysteine-dependent iron-binding site of IRP2 in cellular physiology. The early molecular events in iron-dependent degradation of IRP2 remain to be elucidated. JF - Blood cells, molecules & diseases AU - Bourdon, Emmanuel AU - Kang, Dae-Kyung AU - Ghosh, Manik C AU - Drake, Steven K AU - Wey, Jane AU - Levine, Rodney L AU - Rouault, Tracey A AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. PY - 2003 SP - 247 EP - 255 VL - 31 IS - 2 SN - 1079-9796, 1079-9796 KW - Heptanoates KW - 0 KW - Recombinant Proteins KW - Heme KW - 42VZT0U6YR KW - succinylacetone KW - 51568-18-4 KW - Iron KW - E1UOL152H7 KW - Iron Regulatory Protein 2 KW - EC 4.2.1.3 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Protein Structure, Tertiary -- genetics KW - Humans KW - Heptanoates -- pharmacology KW - Recombinant Proteins -- genetics KW - Heme -- biosynthesis KW - Iron Regulatory Protein 2 -- chemistry KW - Iron -- physiology KW - Cysteine -- genetics KW - Iron Regulatory Protein 2 -- metabolism KW - Iron Regulatory Protein 2 -- genetics KW - Iron Regulatory Protein 2 -- antagonists & inhibitors KW - Iron -- metabolism KW - Cysteine -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73648157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cells%2C+molecules+%26+diseases&rft.atitle=The+role+of+endogenous+heme+synthesis+and+degradation+domain+cysteines+in+cellular+iron-dependent+degradation+of+IRP2.&rft.au=Bourdon%2C+Emmanuel%3BKang%2C+Dae-Kyung%3BGhosh%2C+Manik+C%3BDrake%2C+Steven+K%3BWey%2C+Jane%3BLevine%2C+Rodney+L%3BRouault%2C+Tracey+A&rft.aulast=Bourdon&rft.aufirst=Emmanuel&rft.date=2003-09-01&rft.volume=31&rft.issue=2&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Blood+cells%2C+molecules+%26+diseases&rft.issn=10799796&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-05 N1 - Date created - 2003-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of human Cdc25A stability by Serine 75 phosphorylation is not sufficient to activate a S phase checkpoint. AN - 73645295; 12963847 AB - Degradation of Cdc25A phosphatase is an ubiquitous feature of stress. There are some discrepancies in the reported roles for different phosphorylation sites in the regulation of Cdc25A stability. Using a panel of doxycycline-inducible phosphorylation mutants we show that the stability of human Cdc25A protein is dependent upon phosphorylation at S75. In non-stressed conditions and in non-mitotic cells, Cdc25A is unstable and its stability is regulated in a Chk1-dependent manner. During mitosis, Cdc25A becomes stable and does not undergo degradation after DNA damage. We further show that Chk1 kinase regulates Cdc25A stability after UV irradiation. Similar to Chk1 kinase, p38 MAPK controls Cdc25A protein level after osmotic stress. Using phospho-specific antibodies, we find that both kinases can phosphorylate S75 and S123 in vitro. Inactivation of either Chk1 after UV-irradiation or p38 MAPK after osmotic stress prevents activation of a S phase checkpoint and S75 and S123 phosphorylation. However, introduction of stable Cdc25A (S75A or S75/123A) proteins is not sufficient to overcome this checkpoint. We propose that regulation of human Cdc25A stability by its phosphorylation at S75 may contribute to S phase checkpoint activation only in cooperation with other regulatory mechanisms. JF - Cell cycle (Georgetown, Tex.) AU - Goloudina, Anastasia AU - Yamaguchi, Hiroshi AU - Chervyakova, Daria B AU - Appella, Ettore AU - Fornace, Albert J AU - Bulavin, Dmitry V AD - Gene Response Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2003 SP - 473 EP - 478 VL - 2 IS - 5 SN - 1538-4101, 1538-4101 KW - Multienzyme Complexes KW - 0 KW - Protein Kinases KW - EC 2.7.- KW - CHEK1 protein, human KW - EC 2.7.11.1 KW - Checkpoint Kinase 1 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - CDC25A protein, human KW - EC 3.1.3.48 KW - cdc25 Phosphatases KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Cyclin-Dependent Kinases -- metabolism KW - Ultraviolet Rays KW - HeLa Cells KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Mutagenesis, Site-Directed -- genetics KW - S Phase -- physiology KW - Signal Transduction -- physiology KW - Protein Kinases -- metabolism KW - Phosphorylation KW - Protein Interaction Mapping KW - Mitosis -- physiology KW - Mutation KW - G1 Phase -- physiology KW - Multienzyme Complexes -- metabolism KW - Cysteine Endopeptidases -- metabolism KW - cdc25 Phosphatases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73645295?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cycle+%28Georgetown%2C+Tex.%29&rft.atitle=Regulation+of+human+Cdc25A+stability+by+Serine+75+phosphorylation+is+not+sufficient+to+activate+a+S+phase+checkpoint.&rft.au=Goloudina%2C+Anastasia%3BYamaguchi%2C+Hiroshi%3BChervyakova%2C+Daria+B%3BAppella%2C+Ettore%3BFornace%2C+Albert+J%3BBulavin%2C+Dmitry+V&rft.aulast=Goloudina&rft.aufirst=Anastasia&rft.date=2003-09-01&rft.volume=2&rft.issue=5&rft.spage=473&rft.isbn=&rft.btitle=&rft.title=Cell+cycle+%28Georgetown%2C+Tex.%29&rft.issn=15384101&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-11 N1 - Date created - 2003-09-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cell Cycle. 2003 Sep-Oct;2(5):455-7 [12963843] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Luteal phase dose-response relationships of the antiprogestin CDB-2914 in normally cycling women. AN - 73643850; 12923133 AB - Progesterone receptor modulators have potential therapeutic use in progesterone-dependent conditions such as endometriosis, fibroids and induction of labour. The synthetic steroid CDB-2914 binds to the progesterone and glucocorticoid receptors. In animals it has antiprogestational activity at doses 50-fold less than those required for antiglucocorticoid effects. We evaluated the biological activity, blood levels and safety of CDB-2914 at escalating single doses, in 36 normally cycling women at mid-luteal phase. CDB-2914 at doses of 1-100 mg did not change luteal phase length, but after 200 mg, all women had early endometrial bleeding. Four women with early menses had concurrent functional luteolysis (one at 10, 50, 100 and 200 mg). There were no biochemical or clinical signs of toxicity, and no effect on urinary cortisol or circulating thyroxine, prolactin, adrenocorticotrophic hormone or renin levels. Higher serum equivalents of CDB-2914 were observed by radioimmunoassay than by high performance liquid chromatography detection, indicating a considerable contribution of metabolites. Mid-luteal administration of CDB-2914 antagonizes progesterone action on the endometrium, in a dose-dependent fashion, without apparent antiglucocorticoid effects. Further study of CDB-2914 is needed to determine its clinical role. JF - Human reproduction (Oxford, England) AU - Passaro, Maureen D AU - Piquion, Johann AU - Mullen, Nancy AU - Sutherland, Dorette AU - Zhai, Suoping AU - Figg, William D AU - Blye, Richard AU - Nieman, Lynnette K AD - Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1820 EP - 1827 VL - 18 IS - 9 SN - 0268-1161, 0268-1161 KW - Norpregnadienes KW - 0 KW - Progestins KW - ulipristal KW - 6J5J15Q2X8 KW - Index Medicus KW - Reference Values KW - Menstruation -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Corpus Luteum -- drug effects KW - Menstrual Cycle -- drug effects KW - Time Factors KW - Radioimmunoassay KW - Female KW - Chromatography, High Pressure Liquid KW - Luteolysis KW - Norpregnadienes -- administration & dosage KW - Progestins -- antagonists & inhibitors KW - Luteal Phase -- drug effects KW - Norpregnadienes -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73643850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+reproduction+%28Oxford%2C+England%29&rft.atitle=Luteal+phase+dose-response+relationships+of+the+antiprogestin+CDB-2914+in+normally+cycling+women.&rft.au=Passaro%2C+Maureen+D%3BPiquion%2C+Johann%3BMullen%2C+Nancy%3BSutherland%2C+Dorette%3BZhai%2C+Suoping%3BFigg%2C+William+D%3BBlye%2C+Richard%3BNieman%2C+Lynnette+K&rft.aulast=Passaro&rft.aufirst=Maureen&rft.date=2003-09-01&rft.volume=18&rft.issue=9&rft.spage=1820&rft.isbn=&rft.btitle=&rft.title=Human+reproduction+%28Oxford%2C+England%29&rft.issn=02681161&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-21 N1 - Date created - 2003-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial proteome: altered cytochrome c oxidase subunit levels in prostate cancer. AN - 73643806; 12973739 AB - Laser capture microdissection was combined with reverse phase protein lysate arrays to quantitatively analyze the ratios of mitochondrial encoded cytochrome c oxidase subunits to nuclear encoded cytochrome c oxidase subunits, and to correlate the ratios with malignant progression in human prostate tissue specimens. Cytochrome c oxidase subunits I-III comprise the catalytic core of the enzyme and are all synthesized from mitochondrial DNA. The remaining subunits (IV-VIII) are synthesized from cellular nuclear DNA. A significant (P < 0.001, 30/30 prostate cases) shift in the relative concentrations of nuclear encoded cytochrome c oxidase subunits IV, Vb, and VIc compared to mitochondrial encoded cytochrome c oxidase subunits I and II was noted during the progression of prostate cancer from normal epithelium through premalignant lesions to invasive carcinoma. Significantly, this shift was discovered to begin even in the premalignant stage. Reverse phase protein lysate array-based observations were corroborated with immunohistochemistry, and extended to a few human carcinomas in addition to prostate. This analysis points to a role for nuclear DNA encoded mitochondrial proteins in carcinogenesis; underscoring their potential as targets for therapy while highlighting the need for full characterization of the mitochondrial proteome. JF - Proteomics AU - Herrmann, Paul C AU - Gillespie, John W AU - Charboneau, Lu AU - Bichsel, Verena E AU - Paweletz, Cloud P AU - Calvert, Valerie S AU - Kohn, Elise C AU - Emmert-Buck, Michael R AU - Liotta, Lance A AU - Petricoin, Emanuel F AD - FDA-NCI Clinical Proteomics Program, Laboratory of Pathology, NIH, Bethesda, MD, USA. hermanp@mail.nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1801 EP - 1810 VL - 3 IS - 9 SN - 1615-9853, 1615-9853 KW - Protein Subunits KW - 0 KW - Proteome KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Index Medicus KW - Protein Array Analysis KW - Microdissection KW - Blotting, Western KW - Carcinoma -- chemistry KW - Humans KW - Protein Subunits -- analysis KW - Carcinoma -- enzymology KW - Carcinoma -- diagnosis KW - Immunohistochemistry KW - Male KW - Prostatic Neoplasms -- chemistry KW - Prostatic Neoplasms -- diagnosis KW - Electron Transport Complex IV -- analysis KW - Mitochondria -- chemistry KW - Mitochondria -- enzymology KW - Prostatic Neoplasms -- enzymology KW - Proteome -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73643806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteomics&rft.atitle=Mitochondrial+proteome%3A+altered+cytochrome+c+oxidase+subunit+levels+in+prostate+cancer.&rft.au=Herrmann%2C+Paul+C%3BGillespie%2C+John+W%3BCharboneau%2C+Lu%3BBichsel%2C+Verena+E%3BPaweletz%2C+Cloud+P%3BCalvert%2C+Valerie+S%3BKohn%2C+Elise+C%3BEmmert-Buck%2C+Michael+R%3BLiotta%2C+Lance+A%3BPetricoin%2C+Emanuel+F&rft.aulast=Herrmann&rft.aufirst=Paul&rft.date=2003-09-01&rft.volume=3&rft.issue=9&rft.spage=1801&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-15 N1 - Date created - 2003-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of radiation on normal tissue: consequences and mechanisms. AN - 73642834; 12965273 AB - The use of radiation therapy to treat cancer inevitably involves exposure of normal tissues. As a result, patients may experience symptoms associated with damage to normal tissue during the course of therapy for a few weeks after therapy or months or years later. Symptoms may be due to cell death or wound healing initiated within irradiated tissue, and may be precipitated by exposure to further injury or trauma. Many factors contribute to risk and severity of normal tissue reactions; these factors are site specific and vary with time after treatment. Treatments that reduce the risk or severity of damage to normal tissue or that facilitate the healing of radiation injury are being developed. These could greatly improve the quality of life of patients treated for cancer. JF - The Lancet. Oncology AU - Stone, Helen B AU - Coleman, C Norman AU - Anscher, Mitchell S AU - McBride, William H AD - Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, MD 20892 7440, USA. stoneh@exchange.nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 529 EP - 536 VL - 4 IS - 9 SN - 1470-2045, 1470-2045 KW - Radiation-Protective Agents KW - 0 KW - Index Medicus KW - Animals KW - Radiation-Protective Agents -- therapeutic use KW - Humans KW - Neoplasms -- radiotherapy KW - Radiation Injuries -- prevention & control KW - Radiation Injuries -- pathology KW - Radiotherapy -- adverse effects KW - Radiation Injuries -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73642834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Lancet.+Oncology&rft.atitle=Effects+of+radiation+on+normal+tissue%3A+consequences+and+mechanisms.&rft.au=Stone%2C+Helen+B%3BColeman%2C+C+Norman%3BAnscher%2C+Mitchell+S%3BMcBride%2C+William+H&rft.aulast=Stone&rft.aufirst=Helen&rft.date=2003-09-01&rft.volume=4&rft.issue=9&rft.spage=529&rft.isbn=&rft.btitle=&rft.title=The+Lancet.+Oncology&rft.issn=14702045&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-09 N1 - Date created - 2003-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacillus anthracis lethal toxin induces TNF-alpha-independent hypoxia-mediated toxicity in mice. AN - 73635702; 12952916 AB - Bacillus anthracis lethal toxin (LT) is the major virulence factor of anthrax and reproduces most of the laboratory manifestations of the disease in animals. We studied LT toxicity in BALB/cJ and C57BL/6J mice. BALB/cJ mice became terminally ill earlier and with higher frequency than C57BL/6J mice. Timed histopathological analysis identified bone marrow, spleen, and liver as major affected organs in both mouse strains. LT induced extensive hypoxia. Crisis was due to extensive liver necrosis accompanied by pleural edema. There was no evidence of disseminated intravascular coagulation or renal dysfunction. Instead, analyses revealed hepatic dysfunction, hypoalbuminemia, and vascular/oxygenation insufficiency. Of 50 cytokines analyzed, BALB/cJ mice showed rapid but transitory increases in specific factors including KC, MCP-1/JE, IL-6, MIP-2, G-CSF, GM-CSF, eotaxin, FasL, and IL-1beta. No changes in TNF-alpha occurred. The C57BL/6J mice did not mount a similar cytokine response. These factors were not induced in vitro by LT treatment of toxin-sensitive macrophages. The evidence presented shows that LT kills mice through a TNF-alpha-independent, FasL-independent, noninflammatory mechanism that involves hypoxic tissue injury but does not require macrophage sensitivity to toxin. JF - The Journal of clinical investigation AU - Moayeri, Mahtab AU - Haines, Diana AU - Young, Howard A AU - Leppla, Stephen H AD - National Institutes of Health, NIH, Bethesda, Maryland 20892, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 670 EP - 682 VL - 112 IS - 5 SN - 0021-9738, 0021-9738 KW - Antigens, Bacterial KW - 0 KW - Bacterial Toxins KW - Cytokines KW - Endothelial Growth Factors KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Intercellular Signaling Peptides and Proteins KW - Lymphokines KW - Membrane Glycoproteins KW - Tumor Necrosis Factor-alpha KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - anthrax toxin KW - Abridged Index Medicus KW - Index Medicus KW - Anthrax -- etiology KW - Animals KW - Bone Marrow -- pathology KW - Endothelial Growth Factors -- biosynthesis KW - Liver -- pathology KW - Membrane Glycoproteins -- physiology KW - Cytokines -- biosynthesis KW - Thymus Gland -- pathology KW - Spleen -- pathology KW - Mice KW - Mice, Inbred BALB C KW - Lymphokines -- biosynthesis KW - Mice, Inbred C57BL KW - Intercellular Signaling Peptides and Proteins -- biosynthesis KW - Male KW - Macrophages -- metabolism KW - Tumor Necrosis Factor-alpha -- physiology KW - Hypoxia -- chemically induced KW - Bacterial Toxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73635702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+investigation&rft.atitle=Bacillus+anthracis+lethal+toxin+induces+TNF-alpha-independent+hypoxia-mediated+toxicity+in+mice.&rft.au=Moayeri%2C+Mahtab%3BHaines%2C+Diana%3BYoung%2C+Howard+A%3BLeppla%2C+Stephen+H&rft.aulast=Moayeri&rft.aufirst=Mahtab&rft.date=2003-09-01&rft.volume=112&rft.issue=5&rft.spage=670&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+investigation&rft.issn=00219738&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-25 N1 - Date created - 2003-09-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7011-5 [1908085] Infect Immun. 1991 Oct;59(10):3472-7 [1910002] Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2291-4 [8460135] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10198-201 [8234277] J Gen Microbiol. 1993 Oct;139(10):2459-63 [8254316] Arzneimittelforschung. 1994 Mar;44(3A):420-32 [8185717] Infect Immun. 1984 Sep;45(3):761-7 [6432700] Proc Soc Exp Biol Med. 1985 Jun;179(2):159-62 [2986152] Infect Immun. 1986 Mar;51(3):795-800 [3081444] J Immunol. 1988 Nov 1;141(9):3101-5 [3262679] J Immunol. 1989 Jan 15;142(2):549-53 [2783442] Rev Infect Dis. 1989 Jan-Feb;11 Suppl 1:S289-93 [2784586] Immunol Cell Biol. 1999 Dec;77(6):469-75 [10571666] FEBS Lett. 1999 Nov 26;462(1-2):199-204 [10580119] Biull Eksp Biol Med. 1999 Nov;128(11):511-3 [10640234] Am J Physiol Gastrointest Liver Physiol. 2000 Mar;278(3):G354-66 [10712254] Am J Respir Cell Mol Biol. 2000 Jun;22(6):657-64 [10837361] Biochem J. 2000 Dec 15;352 Pt 3:739-45 [11104681] Int J Med Microbiol. 2000 Oct;290(4-5):421-7 [11111921] Infect Immun. 2001 Feb;69(2):1175-7 [11160016] Hepatology. 2001 Apr;33(4):925-37 [11283857] Mod Pathol. 2001 May;14(5):482-95 [11353060] Curr Opin Hematol. 2001 Sep;8(5):294-8 [11604564] JAMA. 2001 Nov 28;286(20):2549-53 [11722268] JAMA. 2001 Nov 28;286(20):2554-9 [11722269] Emerg Infect Dis. 2001 Nov-Dec;7(6):933-44 [11747719] Am J Med. 2002 Jan;112(1):4-12; discussion 2-3 [11812400] Infect Immun. 1994 Jun;62(6):2590-9 [8188382] J Exp Med. 1994 Sep 1;180(3):783-93 [7520472] Pharmacol Biochem Behav. 1994 Sep;49(1):57-65 [7816890] Mol Microbiol. 1994 Sep;13(6):1093-100 [7854123] Mol Cell Biol. 1996 Sep;16(9):4604-13 [8756616] Mol Med. 1994 Nov;1(1):7-18 [8790597] Eur J Clin Invest. 1996 Sep;26(9):811-9 [8889445] Immunobiology. 1996 Oct;195(4-5):522-49 [8933155] J Biol Chem. 1997 Feb 28;272(9):5375-81 [9038135] Arch Immunol Ther Exp (Warsz). 1997;45(1):49-54 [9090440] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3914-9 [9108079] Mol Med. 1998 Feb;4(2):87-95 [9508786] Science. 1998 May 1;280(5364):734-7 [9563949] Biochem Biophys Res Commun. 1998 Jul 30;248(3):706-11 [9703991] Mol Microbiol. 1998 Jul;29(2):581-91 [9720874] Haematologica. 1998 Aug;83(8):724-32 [9793257] Arch Pathol Lab Med. 1998 Nov;122(11):982-92 [9822127] Semin Hematol. 1999 Jan;36(1 Suppl 1):2-6 [9930556] Exp Parasitol. 1999 Jun;92(2):131-43 [10366538] J Bacteriol. 1962 Jun;83:1274-80 [13866126] Science. 1962 Dec 21;138(3547):1331-3 [14033353] Radiology. 2002 Feb;222(2):305-12 [11818592] Biochem Biophys Res Commun. 2002 Mar 22;292(1):41-4 [11890668] J Endotoxin Res. 2002;8(1):59-67 [11981446] Curr Opin Pulm Med. 2002 Jul;8(4):294-301 [12055392] J Anat. 2002 Jun;200(6):581-97 [12162726] Biochem Biophys Res Commun. 2002 Sep 27;297(3):506-9 [12270123] J Infect Dis. 1966 Apr;116(2):123-38 [4956203] J Infect Dis. 1966 Jun;116(3):377-89 [4957317] Arch Pathol. 1967 Feb;83(2):154-61 [6019568] Fed Proc. 1967 Sep;26(5):1518-21 [4963766] Fed Proc. 1967 Sep;26(5):1554-7 [6051334] J Infect Dis. 1968 Feb;118(1):114-24 [5640983] Gut. 1970 Apr;11(4):352-4 [5428857] Zh Nevropatol Psikhiatr Im S S Korsakova. 1973;73(9):1414-21 [4587698] Neurology. 1975 Jun;25(6):525-30 [1168871] Acta Neuropathol. 1976 Dec 21;36(4):339-45 [1015242] Ann N Y Acad Sci. 1980;353:83-93 [7013615] Am J Trop Med Hyg. 1984 Jan;33(1):144-50 [6696173] Immunology. 1990 Apr;69(4):548-53 [2185985] Pharmacol Biochem Behav. 1990 Jul;36(3):515-9 [2377652] Proc Natl Acad Sci U S A. 1990 Aug;87(16):6263-7 [1696723] Comment In: J Clin Invest. 2003 Sep;112(5):656-8 [12952914] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochrome P450 II D6 gene polymorphisms and the neuroleptic-induced extrapyramidal symptoms in Japanese schizophrenic patients. AN - 73634006; 12960748 AB - The purpose of this study was to examine whether the neuroleptic-induced extrapyramidal symptoms are associated with the CYP2D6 activity. The CYP2D6 gene polymorphisms (CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*10, and CYP2D6*12) were genotyped in 196 normal controls and 320 schizophrenic patients receiving neuroleptics. The relationships with susceptibility to extrapyramidal symptoms (EPS) and tardive dyskinesia, and with steady-state serum haloperidol levels in maintenance therapy, were investigated. The allele frequency of CYP2D6*2 was significantly higher, while that of CYP2D6*10 tended to be higher in the schizophrenic patients susceptible to acute EPS. The steady-state serum haloperidol levels per daily dosage were observed to be significantly higher in schizophrenic patients with the mutant-type homozygote of CYP2D6*2, while this difference was trend level in those of CYP2D6*10. However, no significant difference was observed in the distribution of both CYP2D6*2 (C2938T) and CYP2D6*10 (C188T) polymorphisms between schizophrenic patients with or without tardive dyskinesia. The present results suggest that the homozygotes of CYP2D6*2 and CYP2D6*10 appear to be a susceptibility factor for developing acute EPS in schizophrenic patients and for impaired neuroleptic metabolism in Japanese schizophrenic patients. JF - Psychiatric genetics AU - Inada, Toshiya AU - Senoo, Hisashi AU - Iijima, Yoshimi AU - Yamauchi, Tadamitsu AU - Yagi, Gohei AD - National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba, Japan. inada@med.nagoya-u.ac.jp Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 163 EP - 168 VL - 13 IS - 3 SN - 0955-8829, 0955-8829 KW - Antipsychotic Agents KW - 0 KW - Cytochrome P-450 CYP2D6 KW - EC 1.14.14.1 KW - Index Medicus KW - Reference Values KW - Homozygote KW - Gene Frequency KW - Genetic Predisposition to Disease -- genetics KW - Humans KW - Japan KW - Cytochrome P-450 CYP2D6 -- genetics KW - Basal Ganglia Diseases -- genetics KW - Schizophrenia -- enzymology KW - Polymorphism, Genetic -- genetics KW - Schizophrenia -- genetics KW - Antipsychotic Agents -- adverse effects KW - Basal Ganglia Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73634006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatric+genetics&rft.atitle=Cytochrome+P450+II+D6+gene+polymorphisms+and+the+neuroleptic-induced+extrapyramidal+symptoms+in+Japanese+schizophrenic+patients.&rft.au=Inada%2C+Toshiya%3BSenoo%2C+Hisashi%3BIijima%2C+Yoshimi%3BYamauchi%2C+Tadamitsu%3BYagi%2C+Gohei&rft.aulast=Inada&rft.aufirst=Toshiya&rft.date=2003-09-01&rft.volume=13&rft.issue=3&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Psychiatric+genetics&rft.issn=09558829&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-05 N1 - Date created - 2003-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alterations in genomic profiles during tumor progression in a mouse model of follicular thyroid carcinoma. AN - 73633616; 12869418 AB - The molecular genetics underlying thyroid carcinogenesis is not well understood. We have recently created a mutant mouse by targeting a mutation (PV) into the thyroid hormone receptor beta gene (TRbetaPV mouse). TRbetaPV/PV mice spontaneously develop follicular thyroid carcinoma through pathological progression of hyperplasia, capsular and vascular invasion, anaplasia and eventually metastasis to distant organs. TRbetaPV/PV mice provide an unusual opportunity to study the alterations in gene regulation that occur during thyroid carcinogenesis. To this end, we profiled the genomic changes in the thyroids of TRbetaPV/PV mice at 6 months of age, at which time metastasis had begun. From arrays of 20 000 mouse cDNAs, 185 genes were up-regulated (2-17-fold) and 92 were down-regulated (2-20-fold). Functional clustering of named genes with reported functions (100 genes) indicated that approximately 39% of these genes were tumor-, metastasis/invasion- and cell-cycle-related. Among the activated tumor-related genes identified, cyclin D1, pituitary tumor transforming gene-1, cathespin D and transforming growth factor alpha were also found to over-express in human thyroid cancers. Analyses of the gene profiles suggested that the signaling pathways mediated by thyrotropin, peptide growth factors, transforming growth factor-beta, tumor necrosis factor-alpha and nuclear factor-kappaB were activated, whereas pathways mediated by peroxisome proliferation activated receptor gamma were repressed. These results indicate that complex alterations of multiple signaling pathways contribute to thyroid carcinogenesis. The critical genes associated with thyroid follicular carcinogenesis uncovered in the present study could serve as signature genes for diagnostic purposes, as well as for possible therapeutic targets. JF - Carcinogenesis AU - Ying, Hao AU - Suzuki, Hideyo AU - Furumoto, Hiroko AU - Walker, Robert AU - Meltzer, Paul AU - Willingham, Mark C AU - Cheng, Sheue-Yann AD - Laboratory of Molecular Biology, National Cancer Institute, Winston-Salem, NC 27157-1072, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1467 EP - 1479 VL - 24 IS - 9 SN - 0143-3334, 0143-3334 KW - Receptors, Thyroid Hormone KW - 0 KW - Thyroid Hormone Receptors beta KW - Index Medicus KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Receptors, Thyroid Hormone -- genetics KW - Mice KW - Gene Expression Regulation, Neoplastic KW - Gene Expression Profiling KW - Apoptosis -- genetics KW - Mice, Mutant Strains KW - Carcinoma, Papillary, Follicular KW - Neoplasm Metastasis KW - Cell Cycle -- genetics KW - Mutation KW - Signal Transduction KW - Thyroid Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73633616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alterations+in+genomic+profiles+during+tumor+progression+in+a+mouse+model+of+follicular+thyroid+carcinoma.&rft.au=Ying%2C+Hao%3BSuzuki%2C+Hideyo%3BFurumoto%2C+Hiroko%3BWalker%2C+Robert%3BMeltzer%2C+Paul%3BWillingham%2C+Mark+C%3BCheng%2C+Sheue-Yann&rft.aulast=Ying&rft.aufirst=Hao&rft.date=2003-09-01&rft.volume=24&rft.issue=9&rft.spage=1467&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-21 N1 - Date created - 2003-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A review of the modulation of the startle reflex by affective states and its application in psychiatry. AN - 73628314; 12948786 AB - To provide an overview of startle reflex methodologies applied to the examination of emotional and motivational states in humans and to review the findings in different forms of psychopathology. Pertinent articles were searched mostly via MEDLINE and PsycINFO. The startle reflex is a non-invasive translational tool of research that bridges the gap between animal and human investigations. Startle is used to study fear and anxiety, affective disturbances, sensitization, motivational states, and homeostasis. The startle reflex is highly sensitive to various factors that are of interest in the studies of emotional disorders and has promoted new areas of investigations in psychiatry. However, research in psychiatry is still in its infancy and most findings await replication. Future progress will benefit from the development of innovative and powerful designs tailored to investigate specific disorders. The startle reflex has utility as a research tool to examine trauma-related disorders, fear learning, drug addiction, and to contrast affective states and emotional processing across diagnostic groups, but its usefulness as a diagnostic tool is limited. JF - Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology AU - Grillon, Christian AU - Baas, Johanna AD - National Institute of Mental Health, DHHS, Mood and Anxiety Disorders Program, 15K North Drive, Bldg 15K, MSC 2670, Bethesda, MD 20895, USA. christian.grillon@nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1557 EP - 1579 VL - 114 IS - 9 SN - 1388-2457, 1388-2457 KW - Index Medicus KW - MEDLINE KW - Animals KW - Motivation KW - Anxiety Disorders KW - Psychophysiology KW - Humans KW - Substance-Related Disorders KW - Reflex -- physiology KW - Emotions -- physiology KW - Reflex, Startle -- physiology KW - Psychiatry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73628314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neurophysiology+%3A+official+journal+of+the+International+Federation+of+Clinical+Neurophysiology&rft.atitle=A+review+of+the+modulation+of+the+startle+reflex+by+affective+states+and+its+application+in+psychiatry.&rft.au=Grillon%2C+Christian%3BBaas%2C+Johanna&rft.aulast=Grillon&rft.aufirst=Christian&rft.date=2003-09-01&rft.volume=114&rft.issue=9&rft.spage=1557&rft.isbn=&rft.btitle=&rft.title=Clinical+neurophysiology+%3A+official+journal+of+the+International+Federation+of+Clinical+Neurophysiology&rft.issn=13882457&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-04 N1 - Date created - 2003-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The four distal tyrosines are required for LAT-dependent signaling in FcepsilonRI-mediated mast cell activation. AN - 73626620; 12953098 AB - The linker for activation of T cells (LAT) is an adaptor protein critical for Fc epsilon RI-mediated mast cell activation. LAT is a substrate of the tyrosine kinases activated after TCR and Fc epsilon RI engagement. After phosphorylation of the cytosolic domain of LAT, multiple signaling molecules such as phospholipase C-gamma1, Grb2, and Gads associate with phosphorylated LAT via their SH2 domains. The essential role of the four distal tyrosines in TCR-mediated signaling and T cell development has been demonstrated by experiments using LAT-deficient cell lines and genetically modified mice. To investigate the role of these four tyrosines of LAT in Fc epsilon RI-mediated mast cell activation, bone marrow-derived mast cells from LAT-deficient mice were infected with retroviral vectors designed to express wild-type or mutant LAT. Examination of bone marrow-derived mast cells expressing various tyrosine to phenylalanine mutants in LAT demonstrates a differential requirement for these different binding sites. In these studies, assays of biochemical pathways, degranulation, and cytokine and chemokine release were performed. Finally, the role of these tyrosines was also evaluated in vivo using genetically modified animals. Deletion of all four distal tyrosines, and in particular, loss of the primary phospholipase C-gamma-binding tyrosine had a significant effect on antigen-induced histamine release. JF - The Journal of experimental medicine AU - Saitoh, Shin-ichiroh AU - Odom, Sandra AU - Gomez, Gregorio AU - Sommers, Connie L AU - Young, Howard A AU - Rivera, Juan AU - Samelson, Lawrence E AD - Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 831 EP - 843 VL - 198 IS - 5 SN - 0022-1007, 0022-1007 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Carrier Proteins KW - Lat protein, mouse KW - Membrane Proteins KW - Phosphoproteins KW - Receptors, Antigen, T-Cell KW - Receptors, IgE KW - Recombinant Proteins KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Phosphotyrosine -- immunology KW - Amino Acid Sequence KW - Mice KW - Receptors, Antigen, T-Cell -- immunology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Knockout KW - Mutagenesis KW - Phosphorylation KW - Sequence Alignment KW - Recombinant Proteins -- immunology KW - Sequence Homology, Amino Acid KW - Mast Cells -- immunology KW - Receptors, IgE -- chemistry KW - Phosphoproteins -- genetics KW - Carrier Proteins -- immunology KW - Phosphoproteins -- immunology KW - Carrier Proteins -- genetics KW - Lymphocyte Activation KW - Phosphoproteins -- deficiency KW - Receptors, IgE -- immunology KW - Signal Transduction -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73626620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=The+four+distal+tyrosines+are+required+for+LAT-dependent+signaling+in+FcepsilonRI-mediated+mast+cell+activation.&rft.au=Saitoh%2C+Shin-ichiroh%3BOdom%2C+Sandra%3BGomez%2C+Gregorio%3BSommers%2C+Connie+L%3BYoung%2C+Howard+A%3BRivera%2C+Juan%3BSamelson%2C+Lawrence+E&rft.aulast=Saitoh&rft.aufirst=Shin-ichiroh&rft.date=2003-09-01&rft.volume=198&rft.issue=5&rft.spage=831&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-05 N1 - Date created - 2003-09-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Immunol Lett. 2000 Jan 10;71(1):61-6 [10709787] J Clin Invest. 1999 Jun;103(12):1737-43 [10377180] Immunity. 2000 May;12(5):525-35 [10843385] J Biol Chem. 2000 Jul 28;275(30):23355-61 [10811803] Mol Ther. 2000 Apr;1(4):376-82 [10933956] Int Arch Allergy Immunol. 2001 Jan-Mar;124(1-3):137-41 [11306950] Mol Cell Biol. 2001 Jun;21(11):3763-74 [11340169] Biochem J. 2001 Jun 1;356(Pt 2):461-71 [11368773] Mol Cell Biol. 2001 Jul;21(13):4208-18 [11390650] Nature. 2001 Jul 12;412(6843):186-90 [11449275] J Exp Med. 2001 Jul 16;194(2):135-42 [11457888] Science. 2002 Jun 14;296(5575):2036-40 [12065839] Science. 2002 Jun 14;296(5575):2040-3 [12065840] J Biol Chem. 2002 Jul 12;277(28):25756-74 [11956218] Nat Immunol. 2002 Aug;3(8):741-8 [12089510] J Exp Med. 2003 Jun 2;197(11):1453-65 [12782712] J Immunol. 1980 Jun;124(6):2728-37 [7373045] Nature. 1989 Jan 12;337(6203):187-9 [2521376] Nature. 1989 Mar 30;338(6214):383-4 [2927501] Proc Natl Acad Sci U S A. 1990 Jul;87(14):5327-30 [1695377] Nature. 1992 Jan 2;355(6355):78-80 [1370575] J Immunol. 1992 Jun 1;148(11):3513-9 [1375248] Nature. 1993 May 6;363(6424):45-51 [8479536] Cell. 1993 May 7;73(3):611-20 [8490966] Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8392-6 [7690960] J Biol Chem. 1994 Feb 25;269(8):5918-25 [8119935] J Biol Chem. 1994 Jun 17;269(24):16902-8 [7515887] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11251-5 [7526394] Cell. 1995 Oct 20;83(2):301-11 [7585947] Exp Hematol. 1996 Feb;24(2):324-9 [8641361] J Exp Med. 1996 Jul 1;184(1):71-9 [8691151] J Biol Chem. 1997 Jan 10;272(2):1363-7 [8995445] Oncogene. 1996 Dec 19;13(12):2595-605 [9000133] Cell. 1998 Jan 9;92(1):83-92 [9489702] Immunity. 1998 Nov;9(5):617-26 [9846483] Oncogene. 1998 Dec 17;17(24):3073-82 [9872323] Immunity. 1999 Mar;10(3):323-32 [10204488] J Exp Med. 1999 May 3;189(9):1383-90 [10224278] Blood. 2000 May 15;95(10):3199-203 [10807788] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary folate and selenium affect dimethylhydrazine-induced aberrant crypt formation, global DNA methylation and one-carbon metabolism in rats. AN - 73626376; 12949386 AB - Several observations suggest a role for DNA methylation in cancer pathogenesis. Although both selenium and folate deficiency have been shown to cause global DNA hypomethylation and increased cancer susceptibility, the nutrients have different effects on one-carbon metabolism. Thus, the purpose of this study was to investigate the interactive effects of dietary selenium and folate. Weanling, Fischer-344 rats (n = 23/diet) were fed diets containing 0 or 2.0 mg selenium (as selenite)/kg and 0 or 2.0 mg folate/kg in a 2 x 2 factorial design. After 3 and 4 wk of a 12-wk experiment, 19 rats/diet were injected intraperitoneally with dimethylhydrazine (DMH, 25 mg/kg) and 4 rats/diet were administered saline. Selenium deficiency decreased (P < 0.05) colonic DNA methylation and the activities of liver DNA methyltransferase and betaine homocysteine methyltransferase and increased plasma glutathione concentrations. Folate deficiency increased (P < 0.05) the number of aberrant crypts per aberrant crypt foci, the concentration of colonic S-adenosylhomocysteine and the activity of liver cystathionine synthase. Selenium and folate interacted (P < 0.0001) to influence one-carbon metabolism and cancer susceptibility such that the number of aberrant crypts and the concentrations of plasma homocysteine and liver S-adenosylhomocysteine were the highest and the concentrations of plasma folate and liver S-adenosylmethionine and the activity of liver methionine synthase were the lowest in rats fed folate-deficient diets and supplemental selenium. These results suggest that selenium deprivation ameliorates some of the effects of folate deficiency, probably by shunting the buildup of homocysteine (as a result of folate deficiency) to glutathione. JF - The Journal of nutrition AU - Davis, Cindy D AU - Uthus, Eric O AD - US Department of Agriculture, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202-9034, USA. davisci@mail.nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 2907 EP - 2914 VL - 133 IS - 9 SN - 0022-3166, 0022-3166 KW - Antioxidants KW - 0 KW - Carcinogens KW - Dimethylhydrazines KW - Homocysteine KW - 0LVT1QZ0BA KW - Carbon KW - 7440-44-0 KW - Folic Acid KW - 935E97BOY8 KW - S-Adenosylhomocysteine KW - 979-92-0 KW - 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase KW - EC 2.1.1.13 KW - DNA (Cytosine-5-)-Methyltransferase KW - EC 2.1.1.37 KW - Cystathionine beta-Synthase KW - EC 4.2.1.22 KW - Glutathione KW - GAN16C9B8O KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Injections, Intraperitoneal KW - Homocysteine -- blood KW - Animals KW - Liver -- enzymology KW - Drug Interactions KW - Disease Susceptibility KW - Liver -- metabolism KW - Glutathione -- blood KW - DNA (Cytosine-5-)-Methyltransferase -- metabolism KW - 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase -- metabolism KW - Rats KW - Rats, Inbred F344 KW - Cystathionine beta-Synthase -- metabolism KW - DNA Methylation KW - Deficiency Diseases -- metabolism KW - S-Adenosylhomocysteine -- metabolism KW - Deficiency Diseases -- pathology KW - Deficiency Diseases -- genetics KW - Diet KW - Male KW - Selenium -- deficiency KW - Carcinogens -- administration & dosage KW - Colon -- pathology KW - Folic Acid -- blood KW - Colon -- metabolism KW - Colon -- drug effects KW - Carbon -- metabolism KW - Selenium -- administration & dosage KW - Dimethylhydrazines -- administration & dosage KW - Folic Acid -- administration & dosage KW - Antioxidants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73626376?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=Dietary+folate+and+selenium+affect+dimethylhydrazine-induced+aberrant+crypt+formation%2C+global+DNA+methylation+and+one-carbon+metabolism+in+rats.&rft.au=Davis%2C+Cindy+D%3BUthus%2C+Eric+O&rft.aulast=Davis&rft.aufirst=Cindy&rft.date=2003-09-01&rft.volume=133&rft.issue=9&rft.spage=2907&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-28 N1 - Date created - 2003-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retrotransposons and their recognition of pol II promoters: a comprehensive survey of the transposable elements from the complete genome sequence of Schizosaccharomyces pombe. AN - 73622797; 12952871 AB - The complete DNA sequence of the genome of Schizosaccharomyces pombe provides the opportunity to investigate the entire complement of transposable elements (TEs), their association with specific sequences, their chromosomal distribution, and their evolution. Using homology-based sequence identification, we found that the sequenced strain of S. pombe contained only one family of full-length transposons. This family, Tf2, consisted of 13 full-length copies of a long terminal repeat (LTR) retrotransposon. We found that LTR-LTR recombination of previously existing transposons had resulted in extensive populations of solo LTRs. These included 35 solo LTRs of Tf2, as well as 139 solo LTRs from other Tf families. Phylogenetic analysis of solo Tf LTRs reveals that Tf1 and Tf2 were the most recently active elements within the genome. The solo LTRs also served as footprints for previous insertion events by the Tf retrotransposons. Analysis of 186 genomic insertion events revealed a close association with RNA polymerase II promoters. These insertions clustered in the promoter-proximal regions of genes, upstream of protein coding regions by 100 to 400 nucleotides. The association of Tf insertions with pol II promoters was very similar to the preference previously observed for Tf1 integration. We found that the recently active Tf elements were absent from centromeres and pericentromeric regions of the genome containing tandem tRNA gene clusters. In addition, our analysis revealed that chromosome III has twice the density of insertion events compared to the other two chromosomes. Finally we describe a novel repetitive sequence, wtf, which was also preferentially located on chromosome III, and was often located near solo LTRs of Tf elements. JF - Genome research AU - Bowen, Nathan J AU - Jordan, I King AU - Epstein, Jonathan A AU - Wood, Valerie AU - Levin, Henry L AD - Section on Eukaryotic Transposable Elements, Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1984 EP - 1997 VL - 13 IS - 9 SN - 1088-9051, 1088-9051 KW - Retroelements KW - 0 KW - DNA Polymerase II KW - EC 2.7.7.- KW - Index Medicus KW - Phylogeny KW - Chromosomes, Fungal -- genetics KW - Terminal Repeat Sequences -- genetics KW - Recombination, Genetic KW - Computational Biology KW - Chromosome Mapping KW - Mutagenesis, Insertional KW - Evolution, Molecular KW - Schizosaccharomyces -- genetics KW - Retroelements -- genetics KW - Promoter Regions, Genetic -- genetics KW - Schizosaccharomyces -- chemistry KW - DNA Polymerase II -- genetics KW - Genome, Fungal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73622797?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Retrotransposons+and+their+recognition+of+pol+II+promoters%3A+a+comprehensive+survey+of+the+transposable+elements+from+the+complete+genome+sequence+of+Schizosaccharomyces+pombe.&rft.au=Bowen%2C+Nathan+J%3BJordan%2C+I+King%3BEpstein%2C+Jonathan+A%3BWood%2C+Valerie%3BLevin%2C+Henry+L&rft.aulast=Bowen&rft.aufirst=Nathan&rft.date=2003-09-01&rft.volume=13&rft.issue=9&rft.spage=1984&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 - 2003-10-20 N1 - Date created - 2003-09-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genome Res. 2000 Feb;10(2):174-91 [10673276] Genome Res. 2002 Oct;12(10):1611-8 [12368254] J Virol. 2000 Sep;74(18):8382-9 [10954538] J Biol Chem. 2000 Sep 22;275(38):29800-7 [10882723] Nucleic Acids Res. 2000 Dec 1;28(23):4709-16 [11095681] Bioinformatics. 2000 Oct;16(10):944-5 [11120685] Genome Biol. 2000;1(2):REVIEWS1011 [11178233] Nature. 2001 Feb 15;409(6822):860-921 [11237011] Eukaryot Cell. 2002 Feb;1(1):44-55 [12455970] J Virol. 2003 May;77(9):5451-63 [12692246] Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):215-26 [6694902] Mol Biol Evol. 1988 Nov;5(6):675-90 [2464735] EMBO J. 1990 Oct;9(10):3353-62 [1698615] Mol Cell Biol. 1990 Dec;10(12):6791-8 [2174117] Proteins. 1991;9(3):180-90 [2006136] Genes Dev. 1992 Jan;6(1):117-28 [1309715] EMBO J. 1992 Mar;11(3):1145-53 [1312461] Genes Dev. 1994 Jun 15;8(12):1473-87 [7926746] J Cell Biol. 1994 Oct;127(2):273-85 [7929575] Mol Biol Evol. 1995 Jan;12(1):83-93 [7877499] Mol Cell Biol. 1995 Jun;15(6):3310-7 [7760826] J Mol Evol. 1996 Jan;42(1):59-65 [8576965] Genes Dev. 1996 Mar 1;10(5):634-45 [8598292] Mol Cell Biol. 1996 Oct;16(10):5645-54 [8816477] Science. 1996 Nov 1;274(5288):765-8 [8864112] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7412-6 [9207105] Nucleic Acids Res. 1997 Dec 15;25(24):4876-82 [9396791] Genome Res. 1998 May;8(5):464-78 [9582191] Proc Natl Acad Sci U S A. 1998 May 26;95(11):5906-12 [9600891] Mol Cell Biol. 1998 Nov;18(11):6839-52 [9774697] Genetics. 1999 Apr;151(4):1341-51 [10101161] J Virol. 1999 Jun;73(6):5186-90 [10233986] Genome Res. 1999 Oct;9(10):924-35 [10523521] Nucleic Acids Res. 2001 Jun 1;29(11):2327-37 [11376151] J Virol. 2001 Jul;75(14):6337-47 [11413300] Mol Cell Biol. 2001 Aug;21(16):5374-88 [11463820] Mol Cell Biol. 2001 Oct;21(19):6606-14 [11533248] Genome Res. 2001 Sep;11(9):1527-40 [11544196] Genome Res. 2001 Dec;11(12):2066-74 [11731497] Bioinformatics. 2001 Dec;17(12):1244-5 [11751241] Nature. 2002 Feb 21;415(6874):871-80 [11859360] Curr Opin Genet Dev. 2002 Apr;12(2):178-87 [11893491] Mol Cell. 2002 Jun;9(6):1191-200 [12086617] Genome Res. 2002 Jul;12(7):1048-59 [12097341] Cell. 2002 Aug 23;110(4):521-9 [12202041] Nat Genet. 2002 Sep;32(1):143-7 [12161753] Genome Res. 2002 Oct;12(10):1483-95 [12368240] Mol Biol Evol. 2000 Feb;17(2):320-30 [10677855] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Self-administration of delta9-tetrahydrocannabinol (THC) by drug naive squirrel monkeys. AN - 73622505; 12827345 AB - Interest in therapeutic activities of cannabinoids has been restrained by the fact that they are most often mediated through activation of cannabinoid CB1 receptors, the same receptors that mediate the effects of delta9-tetrahydrocannabinol (THC) and are responsible for the abuse liability of marijuana. Persistent intravenous self-administration of THC by animals was first demonstrated in squirrel monkeys and shown to be mediated by CB1 receptors, but monkeys in the study had a history of cocaine self-administration, raising the possibility that persistent neurobiological adaptations might subsequently predispose animals to self-administer THC. To demonstrate persistent intravenous self-administration of THC in drug-naive squirrel monkeys. Monkeys with no history of exposure to other drugs learned to press a lever for intravenous injections (0.2 ml in 0.2 s) of THC under a 10-response, fixed-ratio schedule with a 60-s time-out after each injection. Acquisition of THC self-administration was rapid and the final schedule was reached in 11-34 sessions. Dose of THC was then varied from 1 to 16 microg/kg per injection with vehicle extinction following each dose of THC. THC maintained significantly higher numbers of self-administered injections per session and higher rates of responding than vehicle at doses of 2, 4 and 8 microg/kg per injection, with maximal rates of responding at 4 microg/kg per injection. Response rates, injections per session and total THC intake per session were two- to three-fold greater in monkeys with no history of exposure to other drugs compared to previous findings in monkeys with a history of cocaine self-administration. THC can act as an effective reinforcer of drug-taking behavior in monkeys with no history of exposure to other drugs, suggesting that self-administration of THC by monkeys provides a reliable animal model of human marijuana abuse. JF - Psychopharmacology AU - Justinova, Zuzana AU - Tanda, Gianluigi AU - Redhi, Godfrey H AU - Goldberg, Steven R AD - Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 135 EP - 140 VL - 169 IS - 2 SN - 0033-3158, 0033-3158 KW - Dronabinol KW - 7J8897W37S KW - Index Medicus KW - Conditioning, Operant -- drug effects KW - Saimiri KW - Marijuana Abuse -- etiology KW - Animals KW - Reinforcement Schedule KW - Injections, Intravenous KW - Dose-Response Relationship, Drug KW - Disease Models, Animal KW - Male KW - Marijuana Abuse -- prevention & control KW - Self Administration -- methods KW - Dronabinol -- pharmacokinetics KW - Dronabinol -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73622505?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Self-administration+of+delta9-tetrahydrocannabinol+%28THC%29+by+drug+naive+squirrel+monkeys.&rft.au=Justinova%2C+Zuzana%3BTanda%2C+Gianluigi%3BRedhi%2C+Godfrey+H%3BGoldberg%2C+Steven+R&rft.aulast=Justinova&rft.aufirst=Zuzana&rft.date=2003-09-01&rft.volume=169&rft.issue=2&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-10 N1 - Date created - 2003-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cannabinoids: reward, dependence, and underlying neurochemical mechanisms--a review of recent preclinical data. AN - 73620914; 12827346 AB - Starting with the discovery of an endogenous brain cannabinoid system with specific receptors and endogenous ligands, research in the cannabinoid field has accelerated dramatically over the last 15 years. Cannabis is the most used illicit psychotropic substance in the world but only recently have reliable preclinical models become available for investigating the rewarding and dependence-producing actions of its psychoactive constituent, delta9-tetrahydrocannabinol (THC). The goal of this review is to examine the various animal models currently available that are being used to facilitate our understanding of the rewarding and dependence-producing actions of cannabinoids, which are central to their abuse liability, and of the neurochemical mechanisms that may underlie these actions of cannabinoids. Recent demonstrations that strong and persistent intravenous self-administration behavior can be obtained in squirrel monkeys using a range of THC doses that are in agreement with the total intake and the single doses of THC normally self-administered by humans smoking marijuana cigarettes provides a reliable and direct tool for assessing the reinforcing effects of THC that are central to its abuse liability. In addition, recent demonstrations of persistent intravenous self-administration of synthetic cannabinoid CB1 receptor agonists by rats and mice and the development of genetically modified mice lacking specific cannabinoid receptors provide convenient rodent models for exploring underlying neurochemical mechanisms. Repeated demonstrations in rats that THC and synthetic CB1 agonists can induce conditioned place preferences or aversions, depending on details of dose and spacing, can reduce the threshold for intracranial self-stimulation behavior under certain conditions, and can serve as effective discriminative stimuli for operant behavior provide less direct, but more rapidly established, measures for investigating the rewarding effects of cannabinoids. Finally, there have been numerous recent reports of major functional interactions between endogenous cannabinoid, opioid, and dopaminergic neurotransmitter systems in areas such as analgesia, physical dependence and tolerance development, and drug reinforcement or reward. This provides an opportunity to search for drugs with the beneficial therapeutic effects of currently available cannabinoids or opioids but without undesirable adverse effects such as abuse liability. JF - Psychopharmacology AU - Tanda, Gianluigi AU - Goldberg, Steven R AD - Psychobiology Section, Medications Discovery Research Branch, National Institute on Drug Abuse, National Institutes of Health, Intramural Research Program, Department of Health and Human Services, Baltimore, MD 21224, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 115 EP - 134 VL - 169 IS - 2 SN - 0033-3158, 0033-3158 KW - Cannabinoids KW - 0 KW - Index Medicus KW - Animals KW - Reward KW - Humans KW - Neurochemistry KW - Cannabinoids -- chemistry KW - Marijuana Abuse -- psychology KW - Cannabinoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73620914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cannabinoids%3A+reward%2C+dependence%2C+and+underlying+neurochemical+mechanisms--a+review+of+recent+preclinical+data.&rft.au=Tanda%2C+Gianluigi%3BGoldberg%2C+Steven+R&rft.aulast=Tanda&rft.aufirst=Gianluigi&rft.date=2003-09-01&rft.volume=169&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-10 N1 - Date created - 2003-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Integrative assessment of multiple pesticides as risk factors for non-Hodgkin's lymphoma among men. AN - 73601275; 12937207 AB - An increased rate of non-Hodgkin's lymphoma (NHL) has been repeatedly observed among farmers, but identification of specific exposures that explain this observation has proven difficult. During the 1980s, the National Cancer Institute conducted three case-control studies of NHL in the midwestern United States. These pooled data were used to examine pesticide exposures in farming as risk factors for NHL in men. The large sample size (n = 3417) allowed analysis of 47 pesticides simultaneously, controlling for potential confounding by other pesticides in the model, and adjusting the estimates based on a prespecified variance to make them more stable. Reported use of several individual pesticides was associated with increased NHL incidence, including organophosphate insecticides coumaphos, diazinon, and fonofos, insecticides chlordane, dieldrin, and copper acetoarsenite, and herbicides atrazine, glyphosate, and sodium chlorate. A subanalysis of these "potentially carcinogenic" pesticides suggested a positive trend of risk with exposure to increasing numbers. Consideration of multiple exposures is important in accurately estimating specific effects and in evaluating realistic exposure scenarios. JF - Occupational and environmental medicine AU - De Roos, A J AU - Zahm, S H AU - Cantor, K P AU - Weisenburger, D D AU - Holmes, F F AU - Burmeister, L F AU - Blair, A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute/NIH, Bethesda, MD, USA. aderoos@fhcrc.org Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1 VL - 60 IS - 9 SN - 1351-0711, 1351-0711 KW - Insecticides KW - 0 KW - Organophosphorus Compounds KW - Pesticides KW - Index Medicus KW - Insecticides -- adverse effects KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Midwestern United States -- epidemiology KW - Male KW - Agricultural Workers' Diseases -- mortality KW - Lymphoma, Non-Hodgkin -- mortality KW - Agricultural Workers' Diseases -- chemically induced KW - Occupational Exposure -- adverse effects KW - Lymphoma, Non-Hodgkin -- chemically induced KW - Pesticides -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73601275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Integrative+assessment+of+multiple+pesticides+as+risk+factors+for+non-Hodgkin%27s+lymphoma+among+men.&rft.au=De+Roos%2C+A+J%3BZahm%2C+S+H%3BCantor%2C+K+P%3BWeisenburger%2C+D+D%3BHolmes%2C+F+F%3BBurmeister%2C+L+F%3BBlair%2C+A&rft.aulast=De+Roos&rft.aufirst=A&rft.date=2003-09-01&rft.volume=60&rft.issue=9&rft.spage=E11&rft.isbn=&rft.btitle=&rft.title=Occupational+and+environmental+medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-16 N1 - Date created - 2003-08-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Occup Environ Med. 1996 Oct;53(10):652-7 [8943828] Occup Environ Med. 1996 Sep;53(9):583-5 [8882113] Occup Med. 1997 Apr-Jun;12(2):269-89 [9220486] Epidemiology. 1997 Nov;8(6):689 [9345674] Am J Ind Med. 1998 Jan;33(1):82-7 [9408531] Cancer Causes Control. 1997 May;8(3):420-43 [9498903] Scand J Work Environ Health. 1998 Aug;24(4):255-61 [9754856] J Occup Environ Med. 1998 Nov;40(11):954-7 [9830600] Occup Environ Med. 1998 Aug;55(8):522-7 [9849538] Cancer. 1999 Mar 15;85(6):1353-60 [10189142] Int J Epidemiol. 2000 Feb;29(1):158-67 [10750618] Cancer Causes Control. 2000 Apr;11(4):373-80 [10843448] Regul Toxicol Pharmacol. 2000 Apr;31(2 Pt 1):117-65 [10854122] Life Sci. 2000 May 19;66(26):2519-25 [10883730] Cancer Epidemiol Biomarkers Prev. 2000 Sep;9(9):895-903 [11008906] Epidemiology. 2000 Nov;11(6):684-8 [11055630] Occup Environ Med. 2001 Jan;58(1):24-30 [11119631] J Occup Environ Med. 2001 Jul;43(7):641-9 [11464396] Cancer Causes Control. 2001 Aug;12(6):509-17 [11519759] Epidemiology. 2001 Nov;12(6):701-9 [11679800] Cancer Epidemiol Biomarkers Prev. 2001 Nov;10(11):1155-63 [11700263] Environ Health Perspect. 2003 Feb;111(2):179-83 [12573902] Res Commun Chem Pathol Pharmacol. 1979 Mar;23(3):597-609 [461978] Br J Cancer. 1981 Feb;43(2):169-76 [7470379] Toxicol Appl Pharmacol. 1983 Apr;68(2):198-205 [6857660] Dev Toxicol Environ Sci. 1983;11:229-40 [6677458] Clin Immunol Immunopathol. 1984 Oct;33(1):13-22 [6478653] JAMA. 1986 Sep 5;256(9):1141-7 [3801091] J Natl Cancer Inst. 1987 May;78(5):899-910 [3471999] Clin Immunol Immunopathol. 1988 Oct;49(1):41-52 [3409555] J Natl Cancer Inst. 1990 Apr 4;82(7):575-82 [2313734] Epidemiology. 1990 Sep;1(5):349-56 [2078610] Lancet. 1992 Feb 29;339(8792):539-41 [1346889] Cancer Res. 1992 May 1;52(9):2447-55 [1568215] Arch Environ Health. 1992 Jul-Aug;47(4):295-301 [1497384] Scand J Work Environ Health. 1992 Aug;18(4):209-15 [1411362] Am J Ind Med. 1993 May;23(5):729-42 [8506851] Scand J Work Environ Health. 1993 Apr;19(2):108-14 [8316777] Semin Hematol. 1993 Oct;30(4):286-96 [8266115] Oncology (Williston Park). 1994 Aug;8(8):67-73; discussion 73-8 [7947004] Epidemiology. 1994 Nov;5(6):612-21 [7841243] Environ Health Perspect. 1994 Nov;102 Suppl 8:33-9 [7851328] J Toxicol Environ Health. 1996 Jun 28;48(3):215-29 [8656446] Environ Health Perspect. 1995 Nov;103 Suppl 8:205-8 [8741784] Am J Ind Med. 1996 Feb;29(2):143-51 [8821357] Am J Ind Med. 1997 Apr;31(4):442-4 [9093659] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unusual locations of involvement by malignancies: Case 2. Metastatic pheochromocytoma to the colon. AN - 73599253; 12947075 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Padmanabhan, H AU - Ehrlich, L D AU - Quazedo, M AU - Fojo, T AU - Louie, A AU - Walther, M AU - Pacak, K AD - National Institutes of Health, Bethesda, MD, USA. Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 3369 EP - 3371 VL - 21 IS - 17 SN - 0732-183X, 0732-183X KW - Vincristine KW - 5J49Q6B70F KW - Dacarbazine KW - 7GR28W0FJI KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Colonoscopy KW - Diagnosis, Differential KW - Humans KW - Adult KW - Vincristine -- administration & dosage KW - Dacarbazine -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Male KW - Urinary Bladder Neoplasms -- pathology KW - Pheochromocytoma -- secondary KW - Colonic Neoplasms -- secondary KW - Colonic Neoplasms -- drug therapy KW - Pheochromocytoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73599253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Unusual+locations+of+involvement+by+malignancies%3A+Case+2.+Metastatic+pheochromocytoma+to+the+colon.&rft.au=Padmanabhan%2C+H%3BEhrlich%2C+L+D%3BQuazedo%2C+M%3BFojo%2C+T%3BLouie%2C+A%3BWalther%2C+M%3BPacak%2C+K&rft.aulast=Padmanabhan&rft.aufirst=H&rft.date=2003-09-01&rft.volume=21&rft.issue=17&rft.spage=3369&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 - 2003-10-02 N1 - Date created - 2003-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis by AID, a molecule critical to immunoglobulin hypermutation, is not caused by an alteration of the precursor nucleotide pool. AN - 73599217; 12943798 AB - The novel cytidine deaminase, AID, plays a critical role in immunoglobulin (Ig) hypermutation. Its possible modes of action include deamination of an RNA transcript that encodes a molecule involved in these processes, deamination of the DNA encoding the variable regions of immunoglobulin genes, or deamination of monomeric cytidine or deoxycytidine (dC) nucleotide generating a mutagenic imbalanced nucleotide pool. We transformed AID into Escherichia coli cells and measured the nucleotide pools at 2 and 6h following induction of expression. Although the majority of the cells expressed AID at the relevant time points, the nucleotide pools were unaltered. In addition, mutagenesis by AID expression in E. coli was not synergistically enhanced in a bacterial strain defective in dUTPase, an enzyme that prevents accumulation of dUTP in the nucleotide pool. Finally, while some AID-GFP fused molecules localized to nucleoids, and a significant portion appears to be distributed throughout the bacterial cell, the highest concentration seemed to localize to the cell poles. Chloramphenicol treatment, which detaches the nucleoids from the membrane, caused a further disassociation of AID-GFP from nucleoids suggesting that AID does not intrinsically bind DNA. These results strongly argue against a role for AID in mutagenesis by deamination of cytosine in the nucleotide pool, and suggest that while AID probably acts by deaminating cytosine in the DNA, it requires a protein partner for efficient localization to DNA. JF - Molecular immunology AU - Diaz, Marilyn AU - Ray, Madhumita AU - Wheeler, Linda J AU - Verkoczy, Laurent K AU - Mathews, Christopher K AD - Laboratory of Molecular Genetics, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA. diaz@niehs.nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 261 EP - 268 VL - 40 IS - 5 SN - 0161-5890, 0161-5890 KW - Cytosine Nucleotides KW - 0 KW - APOBEC-1 Deaminase KW - EC 3.5.4.36 KW - APOBEC1 protein, human KW - Apobec1 protein, rat KW - Cytidine Deaminase KW - EC 3.5.4.5 KW - Index Medicus KW - Rats KW - Animals KW - Escherichia coli -- metabolism KW - Humans KW - Cytosine Nucleotides -- genetics KW - Genes, Reporter KW - Escherichia coli -- genetics KW - Cytosine Nucleotides -- metabolism KW - Cytidine Deaminase -- metabolism KW - Genes, Immunoglobulin KW - Cytidine Deaminase -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73599217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+immunology&rft.atitle=Mutagenesis+by+AID%2C+a+molecule+critical+to+immunoglobulin+hypermutation%2C+is+not+caused+by+an+alteration+of+the+precursor+nucleotide+pool.&rft.au=Diaz%2C+Marilyn%3BRay%2C+Madhumita%3BWheeler%2C+Linda+J%3BVerkoczy%2C+Laurent+K%3BMathews%2C+Christopher+K&rft.aulast=Diaz&rft.aufirst=Marilyn&rft.date=2003-09-01&rft.volume=40&rft.issue=5&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Molecular+immunology&rft.issn=01615890&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-16 N1 - Date created - 2003-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Haematological effects among silk screening workers exposed to 2-ethoxy ethyl acetate. AN - 73598484; 12937203 AB - 2-Ethoxy ethyl acetate (2-EEA) is a solvent with broad industrial and commercial applications. It has been reported to cause hematological toxicity, infertility, and teratogenesis. To investigate the haematological effects in 2-EEA exposed workers. Workers from one silk screening shop (n = 29), using 2-EEA as the major cleaning and printing solvent, were recruited as a high exposure group. Workers with indirect and non-exposure to 2-EEA (n = 56) were recruited as the comparison group. Venous blood was collected for blood routine examination. Air concentration of 2-EEA in this plant was measured by eight hour personal sampling. The geometric mean (GM) of air concentration of 2-EEA in the high exposure group was 7.41 ppm (range 1.35-16.5 pppm). The mean exposure of female workers (GM = 9.34 ppm) was significantly higher than that of male workers (GM = 4.87 ppm). The GM of air 2-EEA concentration in the comparison group was 0.07 ppm (range: non-detectable to 3.62 ppm, n = 26). The haemoglobin and haematocrit in the female high 2-EEA exposure workers were significantly lower than those of female workers in the comparison group. No difference was found between male 2-EEA high exposure and comparison group workers. The haemoglobin, haematocrit, and RBC count in the study population had a significant dose-response relation with air 2-EEA levels. Results suggest that 2-EEA is a haematological toxicant, which leads to anaemic status in high exposure female workers. JF - Occupational and environmental medicine AU - Loh, C-H AU - Shih, T-S AU - Liou, S-H AU - Lin, Y-C AU - Hsieh, A-T AU - Chen, C-Y AU - Liao, G-D AD - Department of Family Medicine & Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, 325 Cheng-Kung Road, Sec. 2, Nei-Hu, Taipei, Taiwan 114, ROC. twdoc@ndmctsgh.edu.tw Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1 VL - 60 IS - 9 SN - 1351-0711, 1351-0711 KW - Acetates KW - 0 KW - Air Pollutants, Occupational KW - Insect Proteins KW - Silk KW - Solvents KW - ethyl acetate KW - 76845O8NMZ KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Air Pollutants, Occupational -- adverse effects KW - Occupational Exposure -- adverse effects KW - Textile Industry KW - Male KW - Female KW - Environmental Monitoring -- methods KW - Hematologic Diseases -- chemically induced KW - Acetates -- adverse effects KW - Occupational Diseases -- blood KW - Textiles KW - Hematologic Diseases -- blood KW - Solvents -- adverse effects KW - Occupational Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73598484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Haematological+effects+among+silk+screening+workers+exposed+to+2-ethoxy+ethyl+acetate.&rft.au=Loh%2C+C-H%3BShih%2C+T-S%3BLiou%2C+S-H%3BLin%2C+Y-C%3BHsieh%2C+A-T%3BChen%2C+C-Y%3BLiao%2C+G-D&rft.aulast=Loh&rft.aufirst=C-H&rft.date=2003-09-01&rft.volume=60&rft.issue=9&rft.spage=E7&rft.isbn=&rft.btitle=&rft.title=Occupational+and+environmental+medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-16 N1 - Date created - 2003-08-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Occup Environ Med. 2003 Feb;60(2):130-5 [12554841] Toxicol Lett. 1999 Sep 20;109(1-2):11-20 [10514026] J Occup Med. 1978 Oct;20(10):675-6 [722353] Toxicol Appl Pharmacol. 1979 Oct;51(1):117-27 [524365] Arch Environ Health. 1983 Nov-Dec;38(6):347-54 [6667035] Voen Med Zh. 1984 Jul;(7):52-3 [6474898] Environ Health Perspect. 1984 Aug;57:75-84 [6499822] Am J Ind Med. 1984;6(6):441-6 [6517073] Br J Ind Med. 1986 Aug;43(8):544-9 [3730304] Br J Ind Med. 1986 Sep;43(9):615-9 [3756113] Scand J Work Environ Health. 1987 Jun;13(3):239-42 [3616552] Am Ind Hyg Assoc J. 1987 Aug;48(8):671-6 [3630916] Am J Ind Med. 1988;14(5):509-26 [3228067] Am J Ind Med. 1988;14(5):527-36 [3265857] Int Arch Occup Environ Health. 1989;61(4):243-7 [2722247] Br J Ind Med. 1989 Jun;46(6):399-406 [2818974] Int Arch Occup Environ Health. 1990;62(2):123-6 [2323830] Br J Ind Med. 1992 Feb;49(2):131-3 [1536820] Leukemia. 1992 Apr;6(4):328-34 [1588795] Am J Ind Med. 1993 Jul;24(1):101-8 [8352288] Int Arch Occup Environ Health. 1993;65(1 Suppl):S47-51 [8406938] Int Arch Occup Environ Health. 1994;65(6):377-80 [8034362] Occup Environ Med. 1999 Oct;56(10):674-8 [10658546] Occup Environ Med. 2000 May;57(5):348-52 [10769301] Arch Environ Health. 2001 Jan-Feb;56(1):20-5 [11256852] Am J Ind Med. 1997 Feb;31(2):148-52 [9028430] Occup Environ Med. 1999 Jun;56(6):378-82 [10474532] Acta Med Scand. 1970 Oct;188(4):277-80 [5479659] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TLP, a novel modulator of TGF-beta signaling, has opposite effects on Smad2- and Smad3-dependent signaling. AN - 73584843; 12941698 AB - Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine signaling to the nucleus through cell surface transmembrane receptor serine/threonine kinases and cytoplasmic effectors, including Smad proteins. We describe a novel modulator of this pathway, TLP (TRAP-1-like protein), which is 25% identical to the previously described Smad4 chaperone, TRAP-1, and shows identical expression patterns in human tissues. Endogenous TLP associates with both active and kinase-deficient TGF-beta and activin type II receptors, but interacts with the common-mediator Smad4 only in the presence of TGF-beta/activin signaling. Overexpression of TLP represses the ability of TGF-beta to induce transcription from SBE-Luc, a Smad3/4-specific reporter, while it potentiates transcription from ARE-Luc, a Smad2/4-specific reporter. Consistent with this, TLP inhibits the formation of Smad3/4 complexes in the absence of effects on phosphorylation of Smad3, while it affects neither Smad2 phosphorylation nor hetero-oligomerization. We propose that TLP might regulate the balance of Smad2 and Smad3 signaling by localizing Smad4 intracellularly, thus contributing to cellular specificity of TGF-beta transcriptional responses in both normal and pathophysiology. JF - The EMBO journal AU - Felici, Angelina AU - Wurthner, Jens U AU - Parks, W Tony AU - Giam, Louise Ruh-yu AU - Reiss, Michael AU - Karpova, Tatiana S AU - McNally, James G AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5055, USA. Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 4465 EP - 4477 VL - 22 IS - 17 SN - 0261-4189, 0261-4189 KW - Carrier Proteins KW - 0 KW - DNA, Complementary KW - DNA-Binding Proteins KW - Intracellular Signaling Peptides and Proteins KW - Membrane Proteins KW - Recombinant Proteins KW - SMAD2 protein, human KW - SMAD3 protein, human KW - SMAD4 protein, human KW - Smad2 Protein KW - Smad3 Protein KW - Smad4 Protein KW - TGFBRAP1 protein, human KW - Trans-Activators KW - Transcription Factors KW - Transforming Growth Factor beta KW - VPS39 protein, human KW - Vesicular Transport Proteins KW - Activins KW - 104625-48-1 KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - COS Cells KW - Humans KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Models, Biological KW - Cloning, Molecular KW - Endocytosis KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Activins -- metabolism KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Signal Transduction KW - Cell Line KW - Trans-Activators -- metabolism KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Transcription Factors -- metabolism KW - Carrier Proteins -- genetics KW - Transcription Factors -- chemistry KW - Transforming Growth Factor beta -- metabolism KW - Transcription Factors -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73584843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=TLP%2C+a+novel+modulator+of+TGF-beta+signaling%2C+has+opposite+effects+on+Smad2-+and+Smad3-dependent+signaling.&rft.au=Felici%2C+Angelina%3BWurthner%2C+Jens+U%3BParks%2C+W+Tony%3BGiam%2C+Louise+Ruh-yu%3BReiss%2C+Michael%3BKarpova%2C+Tatiana+S%3BMcNally%2C+James+G%3BRoberts%2C+Anita+B&rft.aulast=Felici&rft.aufirst=Angelina&rft.date=2003-09-01&rft.volume=22&rft.issue=17&rft.spage=4465&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-28 N1 - Date created - 2003-08-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 2000 Oct 13;103(2):295-309 [11057902] Nature. 1999 May 27;399(6734):371-5 [10360576] J Biol Chem. 2001 Mar 2;276(9):6727-38 [11102446] Traffic. 2001 Feb;2(2):111-23 [11247302] Nature. 2001 May 24;411(6836):494-8 [11373684] J Biol Chem. 2001 Jun 1;276(22):19495-502 [11278302] EMBO J. 2001 Jun 1;20(11):2789-801 [11387212] J Biol Chem. 2001 Jun 8;276(23):19945-53 [11262418] J Cell Biol. 2001 Jul 9;154(1):109-22 [11448994] Nat Cell Biol. 2001 Aug;3(8):708-14 [11483955] EMBO J. 2001 Sep 3;20(17):5008-21 [11532964] J Biol Chem. 2001 Nov 9;276(45):42445-54 [11546807] J Cell Sci. 2001 Dec;114(Pt 24):4359-69 [11792802] Nat Cell Biol. 2002 Feb;4(2):124-33 [11788822] J Biol Chem. 2002 Feb 15;277(7):4883-91 [11729207] Genes Cells. 2002 Mar;7(3):321-31 [11918675] Nat Cell Biol. 2002 May;4(5):394-8 [11988743] J Biol Chem. 2002 May 17;277(20):18046-52 [11877415] J Biol Chem. 1999 Oct 29;274(44):31229-35 [10531318] Nucleic Acids Res. 2000 Jan 1;28(1):231-4 [10592234] Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):49-58 [10708952] Genes Dev. 2000 Mar 15;14(6):627-44 [10733523] J Biol Chem. 2000 Apr 14;275(15):11320-6 [10753944] Mol Cell Biol. 2000 May;20(9):3157-67 [10757800] DNA Res. 2000 Apr 28;7(2):143-50 [10819331] Adv Immunol. 2000;75:115-57 [10879283] J Natl Cancer Inst. 2000 Sep 6;92(17):1388-402 [10974075] Mol Cell Biol. 2002 Jul;22(13):4750-9 [12052882] Genes Dev. 2002 Aug 1;16(15):1867-71 [12154118] Trends Cell Biol. 2002 Jul;12(7):312-5 [12185847] EMBO J. 2002 Sep 16;21(18):4915-26 [12234931] J Cell Biol. 2002 Sep 30;158(7):1239-49 [12356868] Mol Biol Cell. 2002 Nov;13(11):4001-12 [12429842] J Cell Sci. 2002 Dec 15;115(Pt 24):4755-63 [12432064] J Biol Chem. 2002 Dec 27;277(52):51008-16 [12374795] Nat Cell Biol. 2003 May;5(5):410-21 [12717440] EMBO J. 1995 May 15;14(10):2199-208 [7774578] Nature. 1995 Oct 12;377(6549):548-52 [7566156] FEBS Lett. 1995 Dec 18;377(2):243-8 [8543060] EMBO J. 1996 Jan 15;15(2):276-89 [8617203] Cell. 1996 Aug 9;86(3):435-44 [8756725] Cell. 1996 Dec 27;87(7):1215-24 [8980228] J Biol Chem. 1997 Apr 25;272(17):11344-9 [9111041] Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 [9254694] J Biol Chem. 1998 Apr 17;273(16):9365-8 [9545258] Mol Cell. 1998 Mar;1(4):611-7 [9660945] Mol Cell. 1998 Jul;2(1):109-20 [9702197] Mol Cell Biol. 1998 Nov;18(11):6595-604 [9774674] J Biol Chem. 1998 Nov 27;273(48):31770-7 [9822641] Cell. 1998 Dec 11;95(6):779-91 [9865696] J Biol Chem. 1999 Jan 8;274(2):703-9 [9873005] Mol Cell Biol. 2000 Dec;20(24):9346-55 [11094085] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sympathetic innervation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease. AN - 73578010; 12805479 AB - Cardiac sympathetic denervation occurs commonly in Parkinson's disease. This study explored whether analogous denervation occurs in primates with Parkinsonism from systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 6-[18F]Fluorodopamine positron emission tomographic scanning and plasma levels of catecholamines and their deaminated metabolites were used to assess sympathetic and adrenomedullary function in rhesus monkeys, in the untreated state (n = 3), 2 weeks after a series of four MPTP injections, before establishment of Parkinsonism (acute phase, n = 1); a month later, after four more MPTP doses, associated with severe Parkinsonism (subacute phase, n = 1); or more than 2 years from the last dose (remote phase, n = 3), with persistent severe Parkinsonism. A positive control received i.v. 6-hydroxydopamine 1 week before 6-[18F]fluorodopamine scanning. Acute MPTP treatment increased cardiac 6-[18F]fluorodopamine-derived radioactivity, whereas 6-hydroxydopamine markedly decreased cardiac radioactivity, despite similarly low plasma levels of catecholamines and metabolites after either treatment. Subacutely, plasma catecholamines remained decreased, but now with myocardial 6-[18F]fluorodopamine-derived radioactivity also decreased. Remotely, MPTP-treated monkeys had lower plasma catecholamines and higher myocardial 6-[18F]fluorodopamine-derived radioactivity than did untreated animals. The results indicate that in nonhuman primates, systemic MPTP administration produces multiphasic effects on peripheral catecholamine systems, with nearly complete recovery by 2 years. MPTP- and 6-hydroxydopamine-induced changes differ markedly, probably from ganglionic or preganglionic neurotoxicity with the former and more severe cardiac sympathetic neurotoxicity with the latter. Because of multiphasic sympathetic and adrenomedullary effects, without cardioselective sympathetic denervation at any time, the primate MPTP model does not mimic the changes in peripheral catecholamine systems that characterize the human disease. JF - The Journal of pharmacology and experimental therapeutics AU - Goldstein, David S AU - Li, Sheng-Ting AU - Holmes, Courtney AU - Bankiewicz, Krys AD - Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, USA. goldsteind@ninds.nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 855 EP - 860 VL - 306 IS - 3 SN - 0022-3565, 0022-3565 KW - Catechols KW - 0 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Index Medicus KW - Animals KW - Disease Models, Animal KW - Catechols -- blood KW - Macaca mulatta KW - Male KW - MPTP Poisoning -- blood KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- adverse effects KW - Sympathetic Nervous System -- physiopathology KW - MPTP Poisoning -- chemically induced KW - MPTP Poisoning -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73578010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Sympathetic+innervation+in+the+1-methyl-4-phenyl-1%2C2%2C3%2C6-tetrahydropyridine+primate+model+of+Parkinson%27s+disease.&rft.au=Goldstein%2C+David+S%3BLi%2C+Sheng-Ting%3BHolmes%2C+Courtney%3BBankiewicz%2C+Krys&rft.aulast=Goldstein&rft.aufirst=David&rft.date=2003-09-01&rft.volume=306&rft.issue=3&rft.spage=855&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 - 2003-10-03 N1 - Date created - 2003-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic susceptibility and dietary patterns in lung cancer. AN - 73577590; 12928118 AB - Cigarette smoking is the dominant risk factor for lung cancer, but only a minority of smokers ever develops tumors. Though genetic susceptibility is likely to explain some of the variability in risk, results from previous studies of genetic polymorphisms have been inconclusive. As diet may also affect the risk of lung cancer, it is possible that the degree of risk produced by smoking and genetic susceptibility varies, depending on diet. To assess this hypothesis, we conducted a case-control study to examine the effect of cigarette smoking, dietary patterns and variation in genes involved in phase II metabolism. A total of 254 individuals with lung cancer and 184 healthy controls were recruited for the study. To identify persons with similar dietary patterns, cluster analysis was performed using nutrient densities of four major dietary constituents: protein, carbohydrate, animal fat, and dietary fiber. Two groups of individuals were identified with distinct dietary patterns: (1) a group (n=241) with a high intake of animal fat and protein and a low intake of carbohydrates and dietary fiber (the 'unhealthy' pattern) and (2) a group (n=197) with a high intake of fiber and carbohydrate and a low intake of protein and animal fat (the 'healthy' pattern) [corrected]. On stratified analysis, several genotype/dietary pattern combinations were found to affect risk of lung cancer. Smokers who were not homozygous for the most common GSTP1 allele and had a healthy dietary pattern were at significantly lower risk than smokers who were homozygous for the GSTP1 common allele and who had an unhealthy dietary pattern (OR=0.16, 95%CI: 0.04-0.57). Among smokers who were GSTM1 null, persons with a healthy dietary pattern were at lower risk than persons with an unhealthy dietary pattern (OR: 0.46, 95%CI: 0.21-1.01). Among smokers with an unhealthy dietary patterns, persons with a His/His genotype in the exon 3 polymorphism of EPHX1 were at significantly lower risk that persons who were not homozygous. These data suggest that dietary factors may affect the risk imposed by genetic susceptibility at detoxification loci. Adjustments using dietary pattern may be useful in elucidating the effects of polymorphisms in genes responsible for carcinogen metabolism. JF - Lung cancer (Amsterdam, Netherlands) AU - Tsai, Ya-Yu AU - McGlynn, Katherine A AU - Hu, Ying AU - Cassidy, Anna B AU - Arnold, John AU - Engstrom, Paul F AU - Buetow, Kenneth H AD - Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 269 EP - 281 VL - 41 IS - 3 SN - 0169-5002, 0169-5002 KW - Dietary Carbohydrates KW - 0 KW - Dietary Fats KW - Dietary Proteins KW - Isoenzymes KW - GSTP1 protein, human KW - EC 2.5.1.18 KW - Glutathione S-Transferase pi KW - Glutathione Transferase KW - Index Medicus KW - Genetic Variation KW - Humans KW - Aged KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Female KW - Male KW - Lung Neoplasms -- etiology KW - Glutathione Transferase -- pharmacology KW - Smoking -- adverse effects KW - Lung Neoplasms -- genetics KW - Glutathione Transferase -- genetics KW - Genetic Predisposition to Disease KW - Diet KW - Isoenzymes -- genetics KW - Isoenzymes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73577590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.atitle=Genetic+susceptibility+and+dietary+patterns+in+lung+cancer.&rft.au=Tsai%2C+Ya-Yu%3BMcGlynn%2C+Katherine+A%3BHu%2C+Ying%3BCassidy%2C+Anna+B%3BArnold%2C+John%3BEngstrom%2C+Paul+F%3BBuetow%2C+Kenneth+H&rft.aulast=Tsai&rft.aufirst=Ya-Yu&rft.date=2003-09-01&rft.volume=41&rft.issue=3&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=Lung+cancer+%28Amsterdam%2C+Netherlands%29&rft.issn=01695002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-06 N1 - Date created - 2003-08-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Lung Cancer. 2004 May;44(2):271 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vav1 dephosphorylation by the tyrosine phosphatase SHP-1 as a mechanism for inhibition of cellular cytotoxicity. AN - 73569450; 12917349 AB - Here, we present data suggesting a novel mechanism for regulation of natural killer (NK) cell cytotoxicity through inhibitory receptors. Interaction of activation receptors with their ligands on target cells induces cytotoxicity by NK cells. This activation is under negative control by inhibitory receptors that recruit tyrosine phosphatase SHP-1 upon binding major histocompatibility class I on target cells. How SHP-1 blocks the activation pathway is not known. To identify SHP-1 substrates, an HLA-C-specific inhibitory receptor fused to a substrate-trapping mutant of SHP-1 was expressed in NK cells. Phosphorylated Vav1, a regulator of actin cytoskeleton, was the only protein detectably associated with the catalytic site of SHP-1 during NK cell contact with target cells expressing HLA-C. Vav1 trapping was independent of actin polymerization, suggesting that inhibition of cellular cytotoxicity occurs through an early dephosphorylation of Vav1 by SHP-1, which blocks actin-dependent activation signals. Such a mechanism explains how inhibitory receptors can block activating signals induced by different receptors. JF - Molecular and cellular biology AU - Stebbins, Christopher C AU - Watzl, Carsten AU - Billadeau, Daniel D AU - Leibson, Paul J AU - Burshtyn, Deborah N AU - Long, Eric O AD - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 6291 EP - 6299 VL - 23 IS - 17 SN - 0270-7306, 0270-7306 KW - Actins KW - 0 KW - Cell Cycle Proteins KW - HLA-C Antigens KW - Intracellular Signaling Peptides and Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-vav KW - Receptors, Immunologic KW - Receptors, KIR KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - VAV1 protein, human KW - PTPN6 protein, human KW - EC 3.1.3.48 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 6 KW - Protein Tyrosine Phosphatases KW - Index Medicus KW - Cytoskeleton -- metabolism KW - Humans KW - Actins -- ultrastructure KW - Catalytic Domain KW - Actins -- metabolism KW - Recombinant Proteins -- genetics KW - HLA-C Antigens -- genetics KW - Recombinant Fusion Proteins -- metabolism KW - Receptors, Immunologic -- genetics KW - HLA-C Antigens -- metabolism KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Cells, Cultured KW - Receptors, Immunologic -- metabolism KW - Binding, Competitive KW - Recombinant Fusion Proteins -- genetics KW - Cytotoxicity Tests, Immunologic KW - Cytoskeleton -- ultrastructure KW - Mutation KW - Killer Cells, Natural -- metabolism KW - Protein Tyrosine Phosphatases -- metabolism KW - Protein Tyrosine Phosphatases -- genetics KW - Cytotoxicity, Immunologic -- physiology KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73569450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vav1+dephosphorylation+by+the+tyrosine+phosphatase+SHP-1+as+a+mechanism+for+inhibition+of+cellular+cytotoxicity.&rft.au=Stebbins%2C+Christopher+C%3BWatzl%2C+Carsten%3BBilladeau%2C+Daniel+D%3BLeibson%2C+Paul+J%3BBurshtyn%2C+Deborah+N%3BLong%2C+Eric+O&rft.aulast=Stebbins&rft.aufirst=Christopher&rft.date=2003-09-01&rft.volume=23&rft.issue=17&rft.spage=6291&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 - 2003-09-24 N1 - Date created - 2003-08-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 1997 Dec 15;186(12):1965-74 [9396765] Science. 1999 Jul 30;285(5428):727-9 [10426993] Eur J Immunol. 1998 Feb;28(2):716-29 [9521082] Structure. 1998 Mar 15;6(3):249-54 [9551546] Proc Natl Acad Sci U S A. 1998 May 26;95(11):6302-7 [9600960] Mol Cell Biol. 1998 Jul;18(7):3838-50 [9632768] J Exp Med. 1998 Aug 3;188(3):549-59 [9687532] Semin Immunol. 1998 Aug;10(4):329-47 [9695189] J Biol Chem. 1998 Oct 16;273(42):27518-23 [9765283] Cell. 1999 Jan 8;96(1):9-12 [9989492] J Immunol. 1999 Mar 15;162(6):3148-52 [10092764] Immunity. 1999 Mar;10(3):323-32 [10204488] Annu Rev Immunol. 1999;17:89-108 [10358754] Annu Rev Immunol. 1999;17:875-904 [10358776] Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15062-7 [10611338] J Biol Chem. 2000 Feb 11;275(6):4066-71 [10660565] Mol Cell Biol. 2000 Mar;20(5):1461-77 [10669724] J Exp Med. 2001 Nov 19;194(10):1507-17 [11714757] Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14547-52 [11724921] J Clin Invest. 2002 Jan;109(2):161-8 [11805126] Nat Immunol. 2002 Mar;3(3):288-94 [11836527] J Immunol. 2002 Apr 1;168(7):3150-4 [11907066] Biochemistry. 2002 May 14;41(19):6202-10 [11994017] J Exp Med. 2003 Jan 6;197(1):77-85 [12515815] J Cell Biol. 2003 Feb 3;160(3):375-85 [12551955] J Biol Chem. 2003 Feb 14;278(7):4668-74 [12468540] J Immunol. 2003 Jun 15;170(12):6107-14 [12794140] Methods Enzymol. 1991;201:477-82 [1943774] Science. 1995 Jun 23;268(5218):1754-8 [7540771] Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6484-8 [7604018] Immunity. 1995 Dec;3(6):801-9 [8777725] J Biol Chem. 1996 Feb 16;271(7):3856-62 [8632004] J Exp Med. 1996 Dec 1;184(6):2243-50 [8976179] Immunity. 1996 Dec;5(6):629-38 [8986721] J Biol Chem. 1997 Jan 10;272(2):843-51 [8995372] Mol Cell Biol. 1997 Mar;17(3):1346-53 [9032261] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1680-5 [9050838] Immunity. 1997 Jun;6(6):655-61 [9208838] J Exp Med. 1997 Nov 17;186(10):1769-74 [9362537] J Immunol. 2000 Apr 15;164(8):3971-81 [10754287] Science. 2000 Jun 16;288(5473):2051-4 [10856220] Curr Biol. 2000 Jun 29;10(13):777-80 [10898979] Cell. 2000 Sep 1;102(5):625-33 [11007481] J Exp Med. 2000 Oct 2;192(7):1047-58 [11015445] J Exp Med. 2000 Oct 2;192(7):1059-68 [11015446] Science. 2000 Oct 6;290(5489):84-9 [11021804] J Immunol. 2000 Oct 1;165(7):3545-8 [11034353] Cell. 2000 Oct 13;103(2):283-94 [11057901] J Immunol. 2001 Feb 15;166(4):2514-21 [11160312] Annu Rev Immunol. 2001;19:375-96 [11244041] Science. 2001 Jan 12;291(5502):319-22 [11209085] Nat Immunol. 2000 Nov;1(5):419-25 [11062502] J Biol Chem. 2001 Jun 22;276(25):23173-8 [11294838] J Exp Med. 2001 Jun 18;193(12):1413-24 [11413196] Eur J Immunol. 2001 Aug;31(8):2403-10 [11500824] Nature. 2001 Sep 13;413(6852):165-71 [11557981] Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11521-6 [11562472] J Immunol. 2001 Oct 15;167(8):4358-67 [11591760] J Immunol. 2001 Nov 15;167(10):5749-57 [11698448] J Immunol. 1999 Jun 15;162(12):7181-8 [10358164] Eur J Immunol. 1999 Jul;29(7):2223-32 [10427985] Science. 1998 Jan 23;279(5350):509-14 [9438836] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted transgene integration into transgenic mouse fibroblasts carrying the full-length human AAVS1 locus mediated by HSV/AAV rep(+) hybrid amplicon vector. AN - 73568038; 12923568 AB - Herpes simplex virus type 1/adeno-associated virus (HSV/AAV) rep(+) hybrid amplicon vectors containing AAV inverted terminal repeats (ITRs) and rep gene sequences can mediate site-specific integration into the human genome. In this study, we have generated and characterized the first transgenic mice that bear the full-length (8.2 kb) human AAVS1 locus. Immortalized mouse embryonic fibroblasts from this mouse line were transduced with the rep(+), rep(-) (containing only ITRs flanking the transgene) hybrid amplicon vectors, and the standard amplicon vector to determine stable integration frequency and the site of integration. Transduction of transgenic fibroblasts resulted in a 10-fold higher stable integration frequency with rep(+) hybrid amplicon vector than with rep(-) or standard amplicon vectors. Southern blot analysis of genomic DNA from transgenic cells stably transduced with the rep(+) hybrid amplicon vector revealed site-specific integration of transgenes at the AAVS1 locus in 50% of clones. Some site-specific and random integration events were limited to the ITR-flanked transgene cassette. In contrast, transduction of transgenic mouse cells with the rep(-) or standard amplicon vectors resulted in random integrations of the entire rep(-) hybrid amplicon or amplicon DNA that were incorporated into the host genome as a concatenate of various sizes. These results demonstrate for the first time that the genome of transgenic mice bearing the human AAVS1 locus serves as a platform for site-specific integration of AAV ITR-flanked transgene cassettes within the hybrid amplicon vector in the presence of Rep. JF - Gene therapy AU - Bakowska, J C AU - Di Maria, M V AU - Camp, S M AU - Wang, Y AU - Allen, P D AU - Breakefield, X O AD - Cellular Neurology Unit, NINDS, National Institutes of Health, Bethesda, MD, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1691 EP - 1702 VL - 10 IS - 19 SN - 0969-7128, 0969-7128 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Mice, Inbred Strains KW - Animals KW - Genetic Engineering KW - Humans KW - Mice KW - Cell Line, Transformed KW - Mice, Transgenic KW - Transduction, Genetic -- methods KW - Genetic Vectors -- administration & dosage KW - Simplexvirus -- genetics KW - Dependovirus -- genetics KW - Genetic Therapy -- methods KW - Genetic Vectors -- genetics KW - Fibroblasts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73568038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Targeted+transgene+integration+into+transgenic+mouse+fibroblasts+carrying+the+full-length+human+AAVS1+locus+mediated+by+HSV%2FAAV+rep%28%2B%29+hybrid+amplicon+vector.&rft.au=Bakowska%2C+J+C%3BDi+Maria%2C+M+V%3BCamp%2C+S+M%3BWang%2C+Y%3BAllen%2C+P+D%3BBreakefield%2C+X+O&rft.aulast=Bakowska&rft.aufirst=J&rft.date=2003-09-01&rft.volume=10&rft.issue=19&rft.spage=1691&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 - 2003-09-17 N1 - Date created - 2003-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of cutaneous protein kinase C alpha induces keratinocyte apoptosis and intraepidermal inflammation by independent signaling pathways. AN - 73566677; 12928424 AB - Skin keratinocytes are major mediators of host immune responses. The skin is also a target for immunologically based inflammation in many pathological states. Activation of protein kinase C (PKC) can induce cutaneous inflammation, but the precise role of each of six cutaneous PKC isoforms (alpha, delta, epsilon, eta, zeta, mu) that regulate normal skin homeostasis or contribute to skin pathology has not been clarified. We generated transgenic mice that overexpress PKCalpha in the basal layer of the epidermis and the outer root sheath of hair follicles under the regulation of the bovine keratin 5 promoter. K5-PKCalpha transgenic mice exhibit severe intraepidermal neutrophilic inflammation and disruption of the epidermis and upper hair follicles when treated topically with 12-O-tetradecanoylphorbol-13-acetate (TPA). Both TPA and UVB cause apoptosis in transgenic skin, but only TPA evokes intraepidermal inflammation. TPA also induces apoptosis in cultured transgenic keratinocytes, and this is prevented by an AP-1 dominant-negative construct. However, inhibiting AP-1 in vivo does not abrogate intraepidermal inflammation. Transcripts for specific cytokines and chemokines are elevated in TPA-treated cultured transgenic keratinocytes, and conditioned culture medium from these cells promotes neutrophil migration in vitro. Chemokine expression and neutrophil migration are not diminished by inhibiting AP-1. Thus, PKCalpha activation induces keratinocyte apoptosis via an AP-1-dependent pathway and mediates chemokine induction and intraepidermal inflammation independently. This model system will be useful to define specific chemokines regulated by PKCalpha that promote intraepidermal neutrophilic inflammation, a condition that characterizes several human cutaneous diseases such as pustular psoriasis and acute generalized exanthematous pustulosis. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Cataisson, Christophe AU - Joseloff, Elizabeth AU - Murillas, Rodolfo AU - Wang, Alice AU - Atwell, Coralyn AU - Torgerson, Sara AU - Gerdes, Michael AU - Subleski, Jeffrey AU - Gao, Ji-Liang AU - Murphy, Philip M AU - Wiltrout, Robert H AU - Vinson, Charles AU - Yuspa, Stuart H AD - Laboratories of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute/NIH, 37 Convent Drive, Bethesda, MD 20892, USA. Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 2703 EP - 2713 VL - 171 IS - 5 SN - 0022-1767, 0022-1767 KW - Chemokines KW - 0 KW - Cytokines KW - Transcription Factor AP-1 KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Cell Survival -- genetics KW - Cytokines -- biosynthesis KW - Transgenes KW - Chemokines -- biosynthesis KW - Inflammation -- genetics KW - Mice KW - Cell Movement -- genetics KW - Mice, Transgenic KW - Transcription Factor AP-1 -- physiology KW - Inflammation -- enzymology KW - Enzyme Activation -- genetics KW - Mice, Inbred Strains KW - Cells, Cultured KW - Enzyme Activation -- immunology KW - Inflammation -- pathology KW - Protein Kinase C -- metabolism KW - Signal Transduction -- physiology KW - Keratinocytes -- enzymology KW - Apoptosis -- physiology KW - Protein Kinase C -- genetics KW - Epidermis -- metabolism KW - Signal Transduction -- genetics KW - Protein Kinase C -- biosynthesis KW - Keratinocytes -- pathology KW - Keratinocytes -- metabolism KW - Epidermis -- pathology KW - Epidermis -- enzymology KW - Protein Kinase C -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73566677?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+cutaneous+protein+kinase+C+alpha+induces+keratinocyte+apoptosis+and+intraepidermal+inflammation+by+independent+signaling+pathways.&rft.au=Cataisson%2C+Christophe%3BJoseloff%2C+Elizabeth%3BMurillas%2C+Rodolfo%3BWang%2C+Alice%3BAtwell%2C+Coralyn%3BTorgerson%2C+Sara%3BGerdes%2C+Michael%3BSubleski%2C+Jeffrey%3BGao%2C+Ji-Liang%3BMurphy%2C+Philip+M%3BWiltrout%2C+Robert+H%3BVinson%2C+Charles%3BYuspa%2C+Stuart+H&rft.aulast=Cataisson&rft.aufirst=Christophe&rft.date=2003-09-01&rft.volume=171&rft.issue=5&rft.spage=2703&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 - 2003-11-17 N1 - Date created - 2003-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Emission of polycyclic aromatic hydrocarbons from animal carcass incinerators. AN - 73565182; 12922061 AB - This study investigated two batch-type animal carcass waste incinerators, one in a hog farm (HOWI) and the other in a livestock disease control centre (LIWI). Additionally, a medical waste incinerator (MEWI) with a fixed grate for the disposal of biological medical waste was also examined. A GC/MS technique was applied to analyze the concentrations of 21 polycyclic aromatic hydrocarbons (PAHs) species in the stack flue gas, bottom ash and wet scrubber (WSB) effluent. The analytical results indicated that total-PAHs in the stack flue gas for HOWI, LIWI and MEWI were mainly in the gaseous phase. Moreover, the mean total-PAHs concentrations of the stack flue gas for HOWI and LIWI were 1.5 and 1.4 times higher than for MEWI (=391 microg/m(3)), respectively. At the most carcinogenic potencies, the results revealed that the mean BaP+BbF+DBA concentrations in the stack flue gas for HOWI and LIWI were 7.6 and 4.6 times higher than those of MEWI (=1.18 microg/m(3)), respectively. Moreover, during the outbreak of foot-and-mouth disease among pigs in southern Taiwan in 1997, emissions of total-PAHs and BaP+BbF+DBA exceeded 226.2 and 2.3 kg/day, respectively. JF - The Science of the total environment AU - Chen, Shui-Jen AU - Hsieh, Lien-Te AU - Chiu, Shui-Chi AD - Department of Environmental Engineering and Science, National Pingtung University of Science and Technology, Nei Pu 91207, Ping Tung, Taiwan, ROC. chensj@mail.npust.edu.tw Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 61 EP - 76 VL - 313 IS - 1-3 SN - 0048-9697, 0048-9697 KW - Air Pollutants KW - 0 KW - Polycyclic Aromatic Hydrocarbons KW - Index Medicus KW - Swine KW - Environmental Monitoring KW - Animals KW - Incineration KW - Abattoirs KW - Polycyclic Aromatic Hydrocarbons -- analysis KW - Refuse Disposal KW - Air Pollutants -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73565182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Science+of+the+total+environment&rft.atitle=Emission+of+polycyclic+aromatic+hydrocarbons+from+animal+carcass+incinerators.&rft.au=Chen%2C+Shui-Jen%3BHsieh%2C+Lien-Te%3BChiu%2C+Shui-Chi&rft.aulast=Chen&rft.aufirst=Shui-Jen&rft.date=2003-09-01&rft.volume=313&rft.issue=1-3&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=The+Science+of+the+total+environment&rft.issn=00489697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-23 N1 - Date created - 2003-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mycophenolate mofetil for the treatment of scleritis. AN - 73564673; 13129873 AB - To evaluate the usefulness of mycophenolate mofetil (MMF) (CellCept, Roche, Nutley, NJ), an antimetabolite immunosuppressant with a selective antiproliferative effect on T and B lymphocytes, for the treatment of scleritis. Retrospective, noncomparative case series. Eight patients with scleritis treated with MMF in a tertiary referral center. Review of the clinical records of patients evaluated at the National Eye Institute and prescribed MMF for the treatment of scleritis. Control of scleral inflammation, the ability to taper prednisone or other immunosuppressive medications, and adverse events were recorded for each patient. Mycophenolate mofetil was determined to be an effective steroid-sparing agent if the daily prednisone dosage could be reduced by 50% or more and was determined to be an effective adjunctive immunosuppressive agent if the scleral inflammation was controlled in patients with active scleritis. Four patients with diffuse anterior scleritis, two with necrotizing scleritis with inflammation, one with nodular anterior scleritis, and one with nodular anterior and posterior scleritis, were identified. Mycophenolate mofetil administration was initiated as a steroid-sparing agent in 4 patients with controlled scleritis and as an additional immunosuppressive agent in 4 patients with active scleritis receiving concomitant treatment with prednisone and cyclosporine or methotrexate. In 3 of the 4 patients started on MMF as a steroid-sparing agent, the scleritis remained controlled while the prednisone dosage was tapered by more than 50%. One of the patients started on MMF as a steroid-sparing agent had recurrent scleritis, and each of the patients with active scleritis continued to have persistent scleral inflammation requiring additional immunosuppressive therapy. Adverse effects recorded in 4 of the 8 patients included a rash, gastrointestinal symptoms, paresthesias, and laboratory evidence of hepatotoxicity and renal toxicity. Although MMF maybe be useful as a steroid-sparing agent, it was not effective as an adjunctive immunosuppressive agent in patients with active scleritis in our small, tertiary referral series. The adverse effects encountered with the use of MMF in this study cannot be attributed conclusively to MMF and are more likely complications of the multiagent systemic immunosuppressive therapy required for the treatment of recalcitrant scleritis. JF - Ophthalmology AU - Sen, H Nida AU - Suhler, Eric B AU - Al-Khatib, Shadi Q AU - Djalilian, Ali R AU - Nussenblatt, Robert B AU - Buggage, Ronald R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1857, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1750 EP - 1755 VL - 110 IS - 9 SN - 0161-6420, 0161-6420 KW - Immunosuppressive Agents KW - 0 KW - Mycophenolic Acid KW - HU9DX48N0T KW - Index Medicus KW - Drug Evaluation KW - Humans KW - Adult KW - Retrospective Studies KW - Middle Aged KW - Male KW - Female KW - Mycophenolic Acid -- analogs & derivatives KW - Mycophenolic Acid -- therapeutic use KW - Scleritis -- pathology KW - Scleritis -- drug therapy KW - Mycophenolic Acid -- adverse effects KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73564673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ophthalmology&rft.atitle=Mycophenolate+mofetil+for+the+treatment+of+scleritis.&rft.au=Sen%2C+H+Nida%3BSuhler%2C+Eric+B%3BAl-Khatib%2C+Shadi+Q%3BDjalilian%2C+Ali+R%3BNussenblatt%2C+Robert+B%3BBuggage%2C+Ronald+R&rft.aulast=Sen&rft.aufirst=H&rft.date=2003-09-01&rft.volume=110&rft.issue=9&rft.spage=1750&rft.isbn=&rft.btitle=&rft.title=Ophthalmology&rft.issn=01616420&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-30 N1 - Date created - 2003-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation. AN - 73564147; 12917342 AB - Nuclear hormone receptors are ligand-dependent transcriptional regulators that modulate chromatin structure. However, the precise molecular mechanisms by which receptors recruit chromatin-remodeling activity are not fully elucidated. We show that in the absence of its ligand-binding domain, the glucocorticoid receptor (GR) is able to interact with both nuclear receptor coactivators and the BRG1 chromatin-remodeling complex in vivo. Individually, the GR makes direct interactions with BRG1-associated factor 60a (BAF60a) and BAF57, but not with BRG1, BAF155, or BAF170. Further, BAF60a possesses at least two interaction surfaces, one for GR and BRG1 and a second for BAF155 and BAF170. A GR mutant, GR(R488Q), that fails to interact with BAF60a in vitro has reduced chromatin-remodeling activity and reduced transcriptional activity from the promoter assembled as chromatin in vivo. Stable expression of a BAF60a truncation mutant, BAF60a4-140, caused chromatin-specific loss of GR functions in vivo. In the presence of the BAF60a mutant, the GR fails to interact with the BRG1 complex and consequently is also deficient in its ability to activate transcription from chromatin. Thus, in addition to previously identified BAF250, BAF60a may provide another critical and direct link between nuclear receptors and the BRG1 complex that is required for promoter recruitment and subsequent chromatin remodeling. JF - Molecular and cellular biology AU - Hsiao, Pei-Wen AU - Fryer, Christy J AU - Trotter, Kevin W AU - Wang, Weidong AU - Archer, Trevor K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 6210 EP - 6220 VL - 23 IS - 17 SN - 0270-7306, 0270-7306 KW - Chromatin KW - 0 KW - Chromosomal Proteins, Non-Histone KW - Macromolecular Substances KW - Nuclear Proteins KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Glucocorticoid KW - SMARCC1 protein, human KW - SMARCC2 protein, human KW - SMARCD1 protein, human KW - Smarcc1 protein, mouse KW - Smarce1 protein, mouse KW - Transcription Factors KW - SMARCA4 protein, human KW - EC 3.6.1.- KW - Smarca4 protein, mouse KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Chromosomal Proteins, Non-Histone -- genetics KW - Receptor Cross-Talk KW - Humans KW - Bone Neoplasms -- metabolism KW - Osteosarcoma -- metabolism KW - Transcription, Genetic KW - Chromosomal Proteins, Non-Histone -- metabolism KW - Receptors, Glucocorticoid -- metabolism KW - Binding Sites KW - Cells, Cultured KW - Osteosarcoma -- genetics KW - Mutation KW - Signal Transduction KW - Receptors, Glucocorticoid -- genetics KW - Bone Neoplasms -- genetics KW - Nuclear Proteins -- genetics KW - Chromatin -- metabolism KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Nuclear Proteins -- metabolism KW - Transcription Factors -- genetics KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73564147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=BAF60a+mediates+critical+interactions+between+nuclear+receptors+and+the+BRG1+chromatin-remodeling+complex+for+transactivation.&rft.au=Hsiao%2C+Pei-Wen%3BFryer%2C+Christy+J%3BTrotter%2C+Kevin+W%3BWang%2C+Weidong%3BArcher%2C+Trevor+K&rft.aulast=Hsiao&rft.aufirst=Pei-Wen&rft.date=2003-09-01&rft.volume=23&rft.issue=17&rft.spage=6210&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 - 2003-09-24 N1 - Date created - 2003-08-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell. 1986 Aug 29;46(5):645-52 [3742595] J Biol Chem. 2003 Apr 4;278(14):12425-32 [12506123] Science. 1987 Apr 24;236(4800):423-7 [3563519] Genes Dev. 1989 Oct;3(10):1590-601 [2515114] Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10148-52 [1946434] Cell. 1992 Feb 7;68(3):573-83 [1339306] Science. 1992 Mar 20;255(5051):1573-6 [1347958] Genes Dev. 1992 Sep;6(9):1707-15 [1516829] Nucleic Acids Res. 1992 Sep 11;20(17):4525-31 [1408752] Science. 1992 Dec 4;258(5088):1598-604 [1360703] EMBO J. 1993 Nov;12(11):4279-90 [8223438] Mol Cell Biol. 1995 Jan;15(1):26-34 [7799933] Mol Endocrinol. 1994 Sep;8(9):1154-62 [7838148] Cell. 1995 Dec 15;83(6):835-9 [8521507] Genes Dev. 1996 Sep 1;10(17):2117-30 [8804307] Genes Dev. 1996 Sep 1;10(17):2131-44 [8804308] J Mol Endocrinol. 1999 Dec;23(3):255-75 [10601972] Mol Cell Biol. 2000 Mar;20(6):2004-13 [10688647] Curr Opin Genet Dev. 2000 Apr;10(2):187-92 [10753786] J Biol Chem. 2000 May 26;275(21):15645-51 [10747867] J Biol Chem. 2000 Jun 9;275(23):17771-7 [10748103] Genes Dev. 2000 Aug 15;14(16):1992-6 [10950863] Crit Rev Eukaryot Gene Expr. 1996;6(2-3):149-88 [8855387] EMBO J. 1996 Oct 1;15(19):5370-82 [8895581] Gene. 1997 Mar 25;188(1):95-100 [9099865] Nature. 1997 Sep 18;389(6648):251-60 [9305837] Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):492-8 [9435219] Nature. 1998 May 7;393(6680):88-91 [9590696] Curr Opin Genet Dev. 1998 Apr;8(2):140-6 [9610403] Annu Rev Biochem. 1998;67:545-79 [9759497] Genes Dev. 1998 Nov 1;12(21):3343-56 [9808622] Mol Cell. 1999 Feb;3(2):247-53 [10078207] Mol Cell. 1999 Apr;3(4):513-9 [10230404] Endocr Rev. 1999 Jun;20(3):321-44 [10368774] Mol Cell Biol. 1999 Sep;19(9):6164-73 [10454563] Genes Dev. 1999 Sep 15;13(18):2339-52 [10500090] EMBO J. 1999 Oct 1;18(19):5380-8 [10508170] Genes Dev. 2000 Oct 1;14(19):2441-51 [11018012] Mol Cell Biol. 2000 Dec;20(23):8879-88 [11073988] Trends Biochem Sci. 2000 Dec;25(12):619-23 [11116189] Mol Endocrinol. 2001 Jan;15(1):1-16 [11145735] Cell. 2001 Mar 9;104(5):631-4 [11257215] Mol Endocrinol. 2001 Jul;15(7):1077-92 [11435609] Biochem Cell Biol. 2001;79(3):317-24 [11467745] Science. 2001 Nov 30;294(5548):1866-70 [11729302] Annu Rev Biochem. 2002;71:247-73 [12045097] Biochem Cell Biol. 2002;80(3):343-51 [12123287] EMBO J. 2002 Aug 1;21(15):4094-103 [12145209] Nature. 1987 Jan 22-28;325(6102):365-8 [3808033] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacogenetics of stomach cancer. AN - 73549547; 12914384 AB - Conventionally adjustments of the dose of chemotherapeutic treatment could be uneffective in preventing toxicity and response variability. New strategies for individualization of treatment in cancer patients are becoming an emerging issue in the clinical practice. Pharmacogenetics is undoubtedly an important source of information in this respect deepening the complex correlation existing between individual genetic profile and the response to therapy in terms of toxicity and activity. Several polymorphisms, i.e. genetic mutations with a frequency > 1% in a given population, have been described for genes encoding proteins involved in the metabolism of the drugs employed in the treatment of gastric cancer. TS (thymidilate synthase) and DPD (dihydropyrimidine dehydrogenase) polymorphisms are implicated in the development of toxicity and in the efficacy of 5-fluorouracil (5FU). XRCC1 (X-ray cross-complementing group 1), ERCC1 (excision cross-complementing gene) and GSTP1 (glutathione S-transferase) have a role in the development of pharmacoresistance to platinum derivatives. MTHFR (5, 10 methylenetetrahydrofolate reductase) C677T polymorphism is important in methotrexate (MTX) metabolism. UGT1A1 (uridine diphoshate-glucuronosyltransferase 1A1) is involved on irinotecan metabolism. MRP2 (multi-drug resistance associated protein) and MDR1 (multi-drug resistance gene) are involved in irinotecan as well as anthracyclines transport. In conclusion, the clinical applications of pharmacogenetics could represent a new insight to accurately determine the proper drug and dose to be used in each individual patient. JF - I supplementi di Tumori : official journal of Societa italiana di cancerologia ... [et al.] AU - Toffoli, Giuseppe AU - Cecchin, Erika AD - Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Via Pedemontana Occidentale 12, Aviano, PN. PY - 2003 SP - S19 EP - S22 VL - 2 IS - 5 SN - 2283-5423, 2283-5423 KW - Antineoplastic Agents KW - 0 KW - DNA-Binding Proteins KW - Isoenzymes KW - Membrane Transport Proteins KW - Multidrug Resistance-Associated Proteins KW - P-Glycoprotein KW - Proteins KW - X-ray repair cross complementing protein 1 KW - multidrug resistance-associated protein 2 KW - 4AF605U6JN KW - Oxidoreductases Acting on CH-NH Group Donors KW - EC 1.5.- KW - Methylenetetrahydrofolate Reductase (NADPH2) KW - EC 1.5.1.20 KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - GSTP1 protein, human KW - EC 2.5.1.18 KW - Glutathione S-Transferase pi KW - Glutathione Transferase KW - ERCC1 protein, human KW - EC 3.1.- KW - Endonucleases KW - Index Medicus KW - Oxidoreductases Acting on CH-NH Group Donors -- metabolism KW - Polymorphism, Genetic KW - Humans KW - Glutathione Transferase -- metabolism KW - Glucuronosyltransferase -- metabolism KW - Proteins -- metabolism KW - Pharmacogenetics KW - Isoenzymes -- metabolism KW - Biological Availability KW - P-Glycoprotein -- metabolism KW - Biotransformation KW - Drug Resistance, Neoplasm -- genetics KW - DNA-Binding Proteins -- metabolism KW - Drug Resistance, Multiple -- genetics KW - Stomach Neoplasms -- metabolism KW - Stomach Neoplasms -- genetics KW - Antineoplastic Agents -- pharmacokinetics KW - Multidrug Resistance-Associated Proteins -- metabolism KW - Multidrug Resistance-Associated Proteins -- genetics KW - Stomach Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73549547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=I+supplementi+di+Tumori+%3A+official+journal+of+Societa+italiana+di+cancerologia+...+%5Bet+al.%5D&rft.atitle=Pharmacogenetics+of+stomach+cancer.&rft.au=Toffoli%2C+Giuseppe%3BCecchin%2C+Erika&rft.aulast=Toffoli&rft.aufirst=Giuseppe&rft.date=2003-09-01&rft.volume=2&rft.issue=5&rft.spage=S19&rft.isbn=&rft.btitle=&rft.title=I+supplementi+di+Tumori+%3A+official+journal+of+Societa+italiana+di+cancerologia+...+%5Bet+al.%5D&rft.issn=22835423&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-28 N1 - Date created - 2003-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroleptic withdrawal in treatment-resistant patients with schizophrenia: tardive dyskinesia is not associated with supersensitive psychosis. AN - 73522276; 12892869 AB - The objective of this retrospective study was to determine whether tardive dyskinesia (TD) represents a risk factor for supersensitive psychosis (SS) by assessing the effect of medication withdrawal on ratings of psychopathology for 30 days following discontinuation of antipsychotic medication in patients with and without TD. The subjects were 101 treatment-resistant patients with schizophrenia who had been admitted to the inpatient service of Neuroscience Research Hospital (NRH), National Institute of Mental Health, between 1982 and 1994 to undergo studies involving discontinuation of antipsychotic medication. Patients were rated independently on a daily basis on the 22-item Psychiatric Symptom Assessment Scale (PSAS), an extended version of the Brief Psychiatric Rating Scale (BPRS). The overall frequency of TD was 35.6%. Tardive dyskinesia patients were older (p < 0.0006) and had suffered from schizophrenia for a longer time (p < 0.003) than No-TD patients. Repeated measure ANOVA revealed a "time" effect for all subgroups studied. The interaction TD x time, however, was not statistically significant for any of the clusters. Within-group analysis revealed significant differences against baseline for measures of positive symptoms, negative symptoms and abnormal involuntary movements in the No-TD group 3 and 4 weeks after antipsychotic withdrawal. In the TD group, however, the changes were observed only at 4 weeks following antipsychotic discontinuation in just two of the positive symptoms cluster. Between-group analyses revealed that, at baseline, the Mannerisms cluster (abnormal involuntary movements) was significantly higher in the TD group (p < 0.05). No significant differences were observed between any of the remaining clusters at baseline or at different times following drug withdrawal. In conclusion, the relationship between SS and TD could not be confirmed in a cohort of patients with treatment-resistant schizophrenia. In the present study, patients with no TD seemed to deteriorate faster than patients with TD in terms of psychopathology and abnormal involuntary movements. It is possible that both group of patients may undergo supersensitive receptor changes, and that these changes may be more pronounced but potentially reversible in the group without TD. JF - Schizophrenia research AU - Apud, Jose A AU - Egan, Michael F AU - Wyatt, Richard J AD - Neuropsychiatry Branch, National Institute of Mental Health, NIH, Bethesda, MD 20892-1379, USA. apudj@intra.nimh.nih.gov Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 151 EP - 160 VL - 63 IS - 1-2 SN - 0920-9964, 0920-9964 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Demography KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Retrospective Studies KW - Drug Resistance KW - Recurrence KW - Male KW - Female KW - Substance Withdrawal Syndrome -- etiology KW - Substance Withdrawal Syndrome -- epidemiology KW - Antipsychotic Agents -- therapeutic use KW - Dyskinesia, Drug-Induced -- epidemiology KW - Dyskinesia, Drug-Induced -- diagnosis KW - Psychotic Disorders -- etiology KW - Schizophrenia -- drug therapy KW - Antipsychotic Agents -- adverse effects KW - Psychotic Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73522276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Schizophrenia+research&rft.atitle=Neuroleptic+withdrawal+in+treatment-resistant+patients+with+schizophrenia%3A+tardive+dyskinesia+is+not+associated+with+supersensitive+psychosis.&rft.au=Apud%2C+Jose+A%3BEgan%2C+Michael+F%3BWyatt%2C+Richard+J&rft.aulast=Apud&rft.aufirst=Jose&rft.date=2003-09-01&rft.volume=63&rft.issue=1-2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Schizophrenia+research&rft.issn=09209964&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-14 N1 - Date created - 2003-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional analysis of C-TAK1 substrate binding and identification of PKP2 as a new C-TAK1 substrate. AN - 73519984; 12941695 AB - Cdc25C-associated kinase 1 (C-TAK1) has been implicated in cell cycle regulation and Ras signaling through its interactions with two putative substrates, the Cdc25C phosphatase and the MAPK scaffold KSR1. Here, we identify sequence motifs required for stable C-TAK1 association and substrate phosphorylation. Using a mutational approach to disrupt binding of C-TAK1 to KSR1 and Cdc25C, we demonstrate that C-TAK1 contributes to the regulation of these proteins in vivo through the generation of 14-3-3-binding sites. KSR1 proteins defective in C-TAK1 binding had severely reduced phosphorylation at the 14-3-3-binding site in vivo, were constitutively localized to the plasma membrane and had increased biological activity. Disruption of the Cdc25C-C-TAK1 interaction resulted in reduced 14-3-3-binding site phosphorylation and nuclear accumulation of Cdc25C in interphase cells. Finally, utilizing the acquired C-TAK1 binding and substrate phosphorylation data, we identify plakophilin 2 (PKP2) as a novel C-TAK1 substrate. Phosphorylation of PKP2 by C-TAK1 also generates a 14-3-3-binding site that influences PKP2 localization. These findings underscore the importance of C-TAK1 as a regulator of 14-3-3 binding and protein localization. JF - The EMBO journal AU - Müller, Jürgen AU - Ritt, Daniel A AU - Copeland, Terry D AU - Morrison, Deborah K AD - Regulation of Cell Growth Laboratory, Center for Cancer Research, NCI-Frederick, PO Box B, Frederick, MD 21702, USA. Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 4431 EP - 4442 VL - 22 IS - 17 SN - 0261-4189, 0261-4189 KW - 14-3-3 Proteins KW - 0 KW - Cell Cycle Proteins KW - PKP2 protein, human KW - Pkp2 protein, mouse KW - Plakophilins KW - Proteins KW - Recombinant Proteins KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Protein Kinases KW - EC 2.7.- KW - KSR-1 protein kinase KW - EC 2.7.1.- KW - MARK3 protein, human KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDC25C protein, human KW - EC 3.1.3.48 KW - Cdc25c protein, mouse KW - cdc25 Phosphatases KW - Index Medicus KW - Animals KW - COS Cells KW - Humans KW - Mutagenesis, Site-Directed KW - Cell Cycle Proteins -- genetics KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - In Vitro Techniques KW - Molecular Sequence Data KW - Protein Kinases -- genetics KW - Xenopus KW - cdc25 Phosphatases -- genetics KW - Binding Sites -- genetics KW - 3T3 Cells KW - Tyrosine 3-Monooxygenase -- metabolism KW - Mice KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - cdc25 Phosphatases -- metabolism KW - Cell Cycle Proteins -- metabolism KW - Protein Kinases -- metabolism KW - Oocytes -- metabolism KW - Transfection KW - Substrate Specificity KW - Female KW - Protein-Serine-Threonine Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73519984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Functional+analysis+of+C-TAK1+substrate+binding+and+identification+of+PKP2+as+a+new+C-TAK1+substrate.&rft.au=M%C3%BCller%2C+J%C3%BCrgen%3BRitt%2C+Daniel+A%3BCopeland%2C+Terry+D%3BMorrison%2C+Deborah+K&rft.aulast=M%C3%BCller&rft.aufirst=J%C3%BCrgen&rft.date=2003-09-01&rft.volume=22&rft.issue=17&rft.spage=4431&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-28 N1 - Date created - 2003-08-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 2002 Mar 22;277(12):10512-22 [11790773] Genes Dev. 1999 May 1;13(9):1067-72 [10323858] J Biol Chem. 2002 May 3;277(18):16102-15 [11821419] Nat Rev Mol Cell Biol. 2002 Mar;3(3):177-86 [11994738] Mol Cell Biol. 2002 Jul;22(14):4984-96 [12077328] Methods Enzymol. 1991;200:62-81 [1956339] J Biol Chem. 1993 Aug 15;268(23):17309-16 [8349614] J Biol Chem. 1994 Dec 2;269(48):30461-9 [7982962] FEBS Lett. 1995 Mar 20;361(2-3):191-5 [7698321] Cell. 1996 Mar 22;84(6):889-97 [8601312] Curr Opin Cell Biol. 1996 Apr;8(2):197-204 [8791426] Mol Cell Biol. 1996 Nov;16(11):6486-93 [8887677] J Cell Biol. 1996 Nov;135(4):1009-25 [8922383] Genes Dev. 1996 Nov 1;10(21):2684-95 [8946910] Science. 1997 Sep 5;277(5331):1497-501 [9278511] Science. 1997 Sep 5;277(5331):1501-5 [9278512] J Biol Chem. 1997 Oct 24;272(43):27281-7 [9341175] Cell Tissue Res. 1997 Dec;290(3):481-99 [9369526] FEBS Lett. 2000 Jan 21;466(1):91-5 [10648819] Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7835-40 [10869435] Cell Signal. 2000 Dec;12(11-12):703-9 [11152955] J Cell Sci. 2001 May;114(Pt 9):1609-12 [11309192] Oncogene. 2001 Apr 5;20(15):1839-51 [11313932] Nat Cell Biol. 2001 Jul;3(7):628-36 [11433294] Oncogene. 2001 Jul 5;20(30):3949-58 [11494123] J Biol Chem. 2001 Dec 14;276(50):47496-507 [11585834] Mol Cell. 2001 Nov;8(5):983-93 [11741534] J Mol Biol. 2002 Jan 18;315(3):435-46 [11786023] J Biol Chem. 2002 Mar 8;277(10):7913-9 [11756411] Cell. 1997 Dec 26;91(7):961-71 [9428519] Cell Growth Differ. 1998 Mar;9(3):197-208 [9543386] Mol Cell Biol. 1999 Jan;19(1):229-40 [9858547] Cell. 1999 Mar 19;96(6):857-68 [10102273] Microsc Res Tech. 1999 Apr 1;45(1):43-54 [10206153] EMBO J. 1999 Apr 15;18(8):2174-83 [10205171] FEBS Lett. 2002 Feb 20;513(1):53-7 [11911880] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of a receptor-mediated mechanism for intracellular sorting of proinsulin in familial hyperproinsulinemia. AN - 73515446; 12829804 AB - In familial hyperproinsulinemia, specific mutations in the proinsulin gene are linked with a profound increase in circulating plasma proinsulin levels. However, the molecular and cellular basis for this disease remains uncharacterized. Here we investigated how these mutations may disrupt the sorting signal required to target proinsulin to the secretory granules of the regulated secretory pathway, resulting in the unregulated release of proinsulin. Using a combination of molecular modeling and site-directed mutagenesis, we have identified structural molecular motifs in proinsulin that are necessary for correct sorting into secretory granules of endocrine cells. We show that membrane carboxypeptidase E (CPE), previously identified as a prohormone-sorting receptor, is essential for proinsulin sorting. This was demonstrated through short interfering RNA-mediated depletion of CPE and transfection with a dominant negative mutant of CPE in a beta-cell line. Mutant proinsulins found in familial hyperproinsulinemia failed to bind to CPE and were not sorted efficiently. These findings provide evidence that the elevation of plasma proinsulin levels found in patients with familial hyperproinsulinemia is caused by the disruption of CPE-mediated sorting of mutant proinsulins to the regulated secretory pathway. JF - Molecular endocrinology (Baltimore, Md.) AU - Dhanvantari, Savita AU - Shen, Fu-Sheng AU - Adams, Tiffany AU - Snell, Christopher R AU - Zhang, ChunFa AU - Mackin, Robert B AU - Morris, Stephen J AU - Loh, Y Peng AD - Section on Cellular Neurobiology, National Institutes of Health, Bethesda, Maryland 20892-4480, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1856 EP - 1867 VL - 17 IS - 9 SN - 0888-8809, 0888-8809 KW - Protein Sorting Signals KW - 0 KW - Proinsulin KW - 9035-68-1 KW - Carboxypeptidase H KW - EC 3.4.17.10 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Carboxypeptidase H -- metabolism KW - Genes, Dominant KW - Carboxypeptidase H -- genetics KW - Hydrogen-Ion Concentration KW - Humans KW - RNA Interference KW - Mutation KW - Proinsulin -- genetics KW - Proinsulin -- metabolism KW - Proinsulin -- blood KW - Protein Transport UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73515446?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Disruption+of+a+receptor-mediated+mechanism+for+intracellular+sorting+of+proinsulin+in+familial+hyperproinsulinemia.&rft.au=Dhanvantari%2C+Savita%3BShen%2C+Fu-Sheng%3BAdams%2C+Tiffany%3BSnell%2C+Christopher+R%3BZhang%2C+ChunFa%3BMackin%2C+Robert+B%3BMorris%2C+Stephen+J%3BLoh%2C+Y+Peng&rft.aulast=Dhanvantari&rft.aufirst=Savita&rft.date=2003-09-01&rft.volume=17&rft.issue=9&rft.spage=1856&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-11 N1 - Date created - 2003-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Case report: life-threatening hypoglycaemia associated with sulfadoxine-pyrimethamine, a commonly used antimalarial drug. AN - 71593442; 15307435 AB - Due to chloroquine resistance, several African countries have changed their first-line malaria treatment to sulfadoxine-pyrimethamine (SP). In this report, we present a case of hypoglycaemic coma associated with SP, an adverse reaction that is likely to be underreported and expected to occur with greater frequency as the use of SP increases. JF - Transactions of the Royal Society of Tropical Medicine and Hygiene AU - Fairhurst, R M AU - Sadou, B AU - Guindo, A AU - Diallo, D A AU - Doumbo, O K AU - Wellems, T E AD - Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. rfairhurst@niaid.nih.gov PY - 2003 SP - 595 EP - 596 VL - 97 IS - 5 SN - 0035-9203, 0035-9203 KW - Antimalarials KW - 0 KW - Drug Combinations KW - fanasil, pyrimethamine drug combination KW - 37338-39-9 KW - Sulfadoxine KW - 88463U4SM5 KW - Pyrimethamine KW - Z3614QOX8W KW - Index Medicus KW - Infant KW - Humans KW - Male KW - Pyrimethamine -- adverse effects KW - Antimalarials -- adverse effects KW - Malaria, Falciparum -- drug therapy KW - Sulfadoxine -- adverse effects KW - Hypoglycemia -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71593442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transactions+of+the+Royal+Society+of+Tropical+Medicine+and+Hygiene&rft.atitle=Case+report%3A+life-threatening+hypoglycaemia+associated+with+sulfadoxine-pyrimethamine%2C+a+commonly+used+antimalarial+drug.&rft.au=Fairhurst%2C+R+M%3BSadou%2C+B%3BGuindo%2C+A%3BDiallo%2C+D+A%3BDoumbo%2C+O+K%3BWellems%2C+T+E&rft.aulast=Fairhurst&rft.aufirst=R&rft.date=2003-09-01&rft.volume=97&rft.issue=5&rft.spage=595&rft.isbn=&rft.btitle=&rft.title=Transactions+of+the+Royal+Society+of+Tropical+Medicine+and+Hygiene&rft.issn=00359203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-08 N1 - Date created - 2004-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - SMAD5 gene expression, rearrangements, copy number, and amplification at fragile site FRA5C in human hepatocellular carcinoma. AN - 71462363; 14670176 AB - Signaling by the transforming growth factor (TGF)-family members is transduced from the cell surface to the nucleus by the Smad group of intracellular proteins. Because we detected alterations on the long arm of chromosome 5, we examined the status of the SMAD5 gene in human hepatocellular carcinoma (HCC) cell lines and primary HCC. In 16 cell lines, chromosome alterations of chromosome 5 were observed in nine cell lines by fluorescence in situ hybridization (FISH), and an increase in SMAD5 gene copy number relative to the ploidy level was found in eight lines. The breakpoints in unbalanced translocations and deletions frequently occurred near the SMAD5 locus, but apparently did not cause loss of SMAD5. In one cell line, where comparative genomic hybridization showed DNA copy number gain confined to the region 5q31, we detected by FISH high-level amplification of the SMAD5 gene located within the fragile site FRA5C. Semiquantitative polymerase chain reaction did not reveal changes in SMAD5 DNA levels in 15 of 17 primary HCC specimens. In 17 HCC cell lines, SMAD5 mRNA levels were either maintained or upregulated by an increase in gene dosage or another mechanism. Collectively, our results show that SMAD5 undergoes copy number gain and increased expression, rather than loss of expression, and therefore suggest that this gene does not act as a tumor-suppressor gene in HCC. The Hep-40 HCC cell line with high-level amplification and significant overexpression of SMAD5 may be useful in studying the interaction of SMAD5 with other genes. JF - Neoplasia (New York, N.Y.) AU - Zimonjic, Drazen B AU - Durkin, Marian E AU - Keck-Waggoner, Catherine L AU - Park, Sang-Won AU - Thorgeirsson, Snorri S AU - Popescu, Nicholas C AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. PY - 2003 SP - 390 EP - 396 VL - 5 IS - 5 SN - 1522-8002, 1522-8002 KW - DNA-Binding Proteins KW - 0 KW - Phosphoproteins KW - RNA, Messenger KW - SMAD5 protein, human KW - Smad5 Protein KW - Trans-Activators KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Blotting, Northern KW - Cell Nucleus -- metabolism KW - Humans KW - In Situ Hybridization, Fluorescence KW - Cell Line, Tumor KW - Translocation, Genetic KW - DNA -- ultrastructure KW - Gene Deletion KW - Polymerase Chain Reaction KW - RNA, Messenger -- metabolism KW - Blotting, Southern KW - Chromosomes -- ultrastructure KW - Cell Membrane -- metabolism KW - Gene Dosage KW - Signal Transduction KW - Gene Expression Regulation, Neoplastic KW - Phosphoproteins -- genetics KW - Trans-Activators -- biosynthesis KW - Phosphoproteins -- biosynthesis KW - Trans-Activators -- genetics KW - Carcinoma, Hepatocellular -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- biosynthesis KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71462363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasia+%28New+York%2C+N.Y.%29&rft.atitle=SMAD5+gene+expression%2C+rearrangements%2C+copy+number%2C+and+amplification+at+fragile+site+FRA5C+in+human+hepatocellular+carcinoma.&rft.au=Zimonjic%2C+Drazen+B%3BDurkin%2C+Marian+E%3BKeck-Waggoner%2C+Catherine+L%3BPark%2C+Sang-Won%3BThorgeirsson%2C+Snorri+S%3BPopescu%2C+Nicholas+C&rft.aulast=Zimonjic&rft.aufirst=Drazen&rft.date=2003-09-01&rft.volume=5&rft.issue=5&rft.spage=390&rft.isbn=&rft.btitle=&rft.title=Neoplasia+%28New+York%2C+N.Y.%29&rft.issn=15228002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-12 N1 - Date created - 2003-12-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int J Oncol. 2000 Feb;16(2):221-30 [10639563] Leukemia. 2001 Oct;15(10):1582-8 [11587216] EMBO J. 2000 Apr 17;19(8):1745-54 [10775259] Genes Chromosomes Cancer. 2000 Jun;28(2):153-63 [10825000] J Natl Cancer Inst. 2000 Sep 6;92(17):1388-402 [10974075] Nat Rev Cancer. 2001 Dec;1(3):214-21 [11902576] Cancer Cell. 2002 Feb;1(1):89-97 [12086891] Int J Cancer. 2002 Sep 10;101(2):118-27 [12209988] Neoplasia. 2002 Nov-Dec;4(6):531-8 [12407447] Int J Oncol. 1998 Jan;12(1):187-96 [9454904] Oncogene. 2003 Jan 23;22(3):445-50 [12545165] J Mol Diagn. 2003 Feb;5(1):48-53 [12552080] Genomics. 2003 Feb;81(2):105-7 [12620387] Cancer Lett. 2003 Mar 20;192(1):1-17 [12637148] Science. 1976 Jan 16;191(4223):185-7 [942798] Hum Genet. 1984;67(2):136-42 [6430783] Adv Cancer Res. 1986;47:235-81 [3022564] Science. 1987 Jan 16;235(4786):305-11 [3541204] Nucleic Acids Res. 1991 Aug 11;19(15):4293 [1870982] Nature. 1994 Nov 10;372(6502):143-9 [7969446] Cancer Res. 1997 Mar 15;57(6):1166-70 [9067288] Cell. 1997 Apr 18;89(2):215-25 [9108477] Nat Genet. 1997 Apr;15 Spec No:417-74 [9140409] Cancer Res. 1997 Jul 1;57(13):2578-80 [9205057] Cancer Res. 1997 Sep 1;57(17):3779-83 [9288787] Oncogene. 1998 Feb 19;16(7):951-6 [9484787] Cancer Res. 1998 May 15;58(10):2196-9 [9605766] Trends Genet. 1998 Dec;14(12):501-6 [9865156] Hepatology. 1999 Apr;29(4):1208-14 [10094966] Cancer Genet Cytogenet. 1999 May;111(1):37-44 [10326589] Int J Cancer. 1999 Jul 19;82(2):197-202 [10389752] Eur J Biochem. 2000 Dec;267(24):6954-67 [11106403] Genes Dev. 2001 Feb 15;15(4):455-66 [11230153] Trends Genet. 2001 Jun;17(6):339-45 [11377796] Nat Genet. 2001 Oct;29(2):117-29 [11586292] Cancer Res. 2000 Feb 15;60(4):1049-53 [10706123] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clinical characteristics of post-treatment reactions to ivermectin/albendazole for Wuchereria bancrofti in a region co-endemic for Mansonella perstans. AN - 71428054; 14628953 AB - Post-treatment reactions to single-dose ivermectin (200 microg/kg) and albendazole (400 mg) were studied in a filarial endemic region of Mali. The prevalence of Wuchereria bancrofti in this region was 48.3% (69 of 143), and coinfection with Mansonella perstans was common (30 of 40, 75%). Microfilarial levels of M. perstans correlated positively with age (P = 0.006) and with W. bancrofti microfilarial levels (P = 0.006). Forty individuals (28 infected and 12 uninfected) were treated, with mild post-treatment reactions occurring in 35.7% (7 of 28) of the W. bancrofti-infected subjects. Reaction severity correlated with pretreatment W. bancrofti microfilarial levels (P = 0.001). There were no significant differences in the prevalence or severity of post-treatment reactions in those who were co-infected with M. perstans. It is concluded that co-infection with M. perstans does not significantly alter the post-treatment reaction profile to single-dose ivermectin/albendazole in W. bancrofti infection in this community, and that acute post-treatment reactions should not limit patient compliance in community-based programs to eliminate lymphatic filariasis. JF - The American journal of tropical medicine and hygiene AU - Keiser, Paul B AU - Coulibaly, Yaya I AU - Keita, Falaye AU - Traore, Diakaridia AU - Diallo, Abdallah AU - Diallo, Dapa A AU - Semnani, Roshanak T AU - Doumbo, Ogobara K AU - Traore, Sekou F AU - Klion, Amy D AU - Nutman, Thomas B AD - Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425, USA. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 331 EP - 335 VL - 69 IS - 3 SN - 0002-9637, 0002-9637 KW - Filaricides KW - 0 KW - Ivermectin KW - 70288-86-7 KW - Albendazole KW - F4216019LN KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Humans KW - Aged KW - Outcome Assessment (Health Care) KW - Mali -- epidemiology KW - Drug Therapy, Combination KW - Mansonella KW - Wuchereria bancrofti KW - Adverse Drug Reaction Reporting Systems KW - Adult KW - Surveys and Questionnaires KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Prevalence KW - Albendazole -- adverse effects KW - Filaricides -- adverse effects KW - Ivermectin -- adverse effects KW - Filariasis -- blood KW - Ivermectin -- administration & dosage KW - Filaricides -- administration & dosage KW - Filariasis -- epidemiology KW - Albendazole -- administration & dosage KW - Filariasis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71428054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+tropical+medicine+and+hygiene&rft.atitle=Clinical+characteristics+of+post-treatment+reactions+to+ivermectin%2Falbendazole+for+Wuchereria+bancrofti+in+a+region+co-endemic+for+Mansonella+perstans.&rft.au=Keiser%2C+Paul+B%3BCoulibaly%2C+Yaya+I%3BKeita%2C+Falaye%3BTraore%2C+Diakaridia%3BDiallo%2C+Abdallah%3BDiallo%2C+Dapa+A%3BSemnani%2C+Roshanak+T%3BDoumbo%2C+Ogobara+K%3BTraore%2C+Sekou+F%3BKlion%2C+Amy+D%3BNutman%2C+Thomas+B&rft.aulast=Keiser&rft.aufirst=Paul&rft.date=2003-09-01&rft.volume=69&rft.issue=3&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+tropical+medicine+and+hygiene&rft.issn=00029637&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-10 N1 - Date created - 2003-11-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mudpies and magpies: iron at the extremes. AN - 71392135; 14626746 JF - Journal of the American Pharmacists Association : JAPhA AU - Wick, Jeannette Y AD - National Cancer Institute, National Institutes of Health, Bethesda, Md., USA. JYWickRPh@aol.com PY - 2003 SP - 556 EP - 560 VL - 43 IS - 5 SN - 1544-3191, 1544-3191 KW - Iron KW - E1UOL152H7 KW - Index Medicus KW - Infant KW - Humans KW - Adolescent KW - Female KW - Child, Preschool KW - Anemia, Hypochromic -- physiopathology KW - Anemia, Iron-Deficiency -- etiology KW - Acidosis -- physiopathology KW - Iron -- administration & dosage KW - Anemia, Iron-Deficiency -- drug therapy KW - Iron -- adverse effects KW - Acidosis -- diagnosis KW - Iron -- therapeutic use KW - Acidosis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71392135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Pharmacists+Association+%3A+JAPhA&rft.atitle=Mudpies+and+magpies%3A+iron+at+the+extremes.&rft.au=Wick%2C+Jeannette+Y&rft.aulast=Wick&rft.aufirst=Jeannette&rft.date=2003-09-01&rft.volume=43&rft.issue=5&rft.spage=556&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Pharmacists+Association+%3A+JAPhA&rft.issn=15443191&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-17 N1 - Date created - 2003-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Bayesian approach for joint modeling of cluster size and subunit-specific outcomes. AN - 71347343; 14601753 AB - In applications that involve clustered data, such as longitudinal studies and developmental toxicity experiments, the number of subunits within a cluster is often correlated with outcomes measured on the individual subunits. Analyses that ignore this dependency can produce biased inferences. This article proposes a Bayesian framework for jointly modeling cluster size and multiple categorical and continuous outcomes measured on each subunit. We use a continuation ratio probit model for the cluster size and underlying normal regression models for each of the subunit-specific outcomes. Dependency between cluster size and the different outcomes is accommodated through a latent variable structure. The form of the model facilitates posterior computation via a simple and computationally efficient Gibbs sampler. The approach is illustrated with an application to developmental toxicity data, and other applications, to joint modeling of longitudinal and event time data, are discussed. JF - Biometrics AU - Dunson, David B AU - Chen, Zhen AU - Harry, Jean AD - Biostatistics Branch, MD A3-03, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA. dunson1@niehs.nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 521 EP - 530 VL - 59 IS - 3 SN - 0006-341X, 0006-341X KW - Ethylene Glycol KW - FC72KVT52F KW - Index Medicus KW - Animals KW - Biometry KW - Ethylene Glycol -- toxicity KW - Models, Statistical KW - Mice KW - Models, Biological KW - Female KW - Pregnancy KW - Embryonic and Fetal Development -- drug effects KW - Bayes Theorem KW - Cluster Analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71347343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=A+Bayesian+approach+for+joint+modeling+of+cluster+size+and+subunit-specific+outcomes.&rft.au=Dunson%2C+David+B%3BChen%2C+Zhen%3BHarry%2C+Jean&rft.aulast=Dunson&rft.aufirst=David&rft.date=2003-09-01&rft.volume=59&rft.issue=3&rft.spage=521&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-27 N1 - Date created - 2003-11-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Biometrics. 2005 Sep;61(3):862-6; discussion 866-7 [16135040] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of naphthalmustine, a nitrogen mustard derivative of naphthalimide as a rationally-designed anticancer agent. AN - 71323256; 14582700 AB - Naphthalmustine, 2-[2-[bis-(2-chloroethyl)amino]ethyl]-1H-benz[de]isoquinoline-1,3-dione (Compound 1) has been synthesized as a rationally designed new anticancer agent from N-(2-bromoethyl)naphthalimide. Its chemical alkylating activity exceeded that of nor-HN2 used as standard compound for comparison. Its antitumour efficacy was assessed in vivo in two murine ascites tumours namely Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. The clinical drug cyclophosphamide and the experimental compound mitonafide were used as positive controls for comparison. Compound 1 has displayed substantial and reproducible antitumoural activity in these tumours since very high remission times of treated animals were observed. Significant increase in the life span of mice bearing highly advanced tumour for 10 days before the drug challenge was also noted after its treatment. Its LD50 value was 200 mg/Kg by single i.p. injection. Its toxicity was also assessed in vivo in normal and in S-180 bearing mice by measuring drug-induced changes in hematological parameters, femoral bone marrow and splenic cellularity sequentially on days 9, 15 and 21 following drug treatment at the optimum dose of 12 mg/kg from day 1 to 7. The results indicated that the compound did not adversely affect hematopoiesis. Drug-induced hepatotoxicity and nephrotoxicity were also evaluated on those days but no such toxicities were detected. Naphthalmustine inhibits the synthesis of DNA and RNA in S-180 tumour cells. It was further screened in vitro in 4 different human tumour cell lines but no significant activity was observed in those lines. JF - Journal of experimental & clinical cancer research : CR AU - Pain, A AU - Samanta, S AU - Dutta, S AU - Saxena, A K AU - Shanmugavel, M AU - Kampasi, H AU - Qazi, G N AU - Sanyal, U AD - Dept. of Anticancer Drug Development, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 411 EP - 418 VL - 22 IS - 3 SN - 0392-9078, 0392-9078 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Isoquinolines KW - Nitrogen Mustard Compounds KW - naphthalmustine KW - Index Medicus KW - Neoplasm Transplantation KW - Molecular Structure KW - Animals KW - Survival Rate KW - Humans KW - Cell Division -- drug effects KW - Mice KW - Cell Line, Tumor KW - Male KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Nitrogen Mustard Compounds -- chemical synthesis KW - Isoquinolines -- adverse effects KW - Drug Design KW - Nitrogen Mustard Compounds -- pharmacology KW - Isoquinolines -- pharmacology KW - Isoquinolines -- therapeutic use KW - Nitrogen Mustard Compounds -- therapeutic use KW - Antineoplastic Agents, Alkylating -- chemical synthesis KW - Nitrogen Mustard Compounds -- adverse effects KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Isoquinolines -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71323256?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Evaluation+of+naphthalmustine%2C+a+nitrogen+mustard+derivative+of+naphthalimide+as+a+rationally-designed+anticancer+agent.&rft.au=Pain%2C+A%3BSamanta%2C+S%3BDutta%2C+S%3BSaxena%2C+A+K%3BShanmugavel%2C+M%3BKampasi%2C+H%3BQazi%2C+G+N%3BSanyal%2C+U&rft.aulast=Pain&rft.aufirst=A&rft.date=2003-09-01&rft.volume=22&rft.issue=3&rft.spage=411&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-20 N1 - Date created - 2003-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Computational analysis of mutation spectra. AN - 71314601; 14582516 AB - Mutation frequencies vary along a nucleotide sequence, and nucleotide positions with an exceptionally high mutation frequency are called hotspots. Mutation hotspots in DNA often reflect intrinsic properties of the mutation process, such as the specificity with which mutagens interact with nucleic acids and the sequence-specificity of DNA repair/replication enzymes. They might also reflect structural and functional features of target protein or RNA sequences in which they occur. The determinants of mutation frequency and specificity are complex and there are many analytical methods for their study. This paper discusses computational approaches to analysing mutation spectra (distribution of mutations along the target genes) that include many detectable (mutable) positions. The following methods are reviewed: mutation hotspot prediction; pairwise and multiple comparisons of mutation spectra; derivation of a consensus sequence; and analysis of correlation between nucleotide sequence features and mutation spectra. Spectra of spontaneous and induced mutations are used for illustration of the complexities and pitfalls of such analyses. In general, the DNA sequence context of mutation hotspots is a fingerprint of interactions between DNA and DNA repair/replication/modification enzymes, and the analysis of hotspot context provides evidence of such interactions. JF - Briefings in bioinformatics AU - Rogozin, Igor B AU - Babenko, Vladimir N AU - Milanesi, Luciano AU - Pavlov, Youri I AD - National Center for Biotechnology Information NLM/NIH, Bethesda, MD 20894, USA. rogozin@ncbi.nlm.nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 210 EP - 227 VL - 4 IS - 3 SN - 1467-5463, 1467-5463 KW - Mutagens KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Software KW - Animals KW - Base Composition KW - DNA Repair KW - DNA -- metabolism KW - Humans KW - Genes, Immunoglobulin KW - Computational Biology KW - Nucleic Acid Conformation KW - Base Sequence KW - Amino Acid Motifs KW - Databases, Nucleic Acid KW - Mutagens -- metabolism KW - DNA -- genetics KW - Molecular Sequence Data KW - Statistics as Topic KW - DNA Mutational Analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71314601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Briefings+in+bioinformatics&rft.atitle=Computational+analysis+of+mutation+spectra.&rft.au=Rogozin%2C+Igor+B%3BBabenko%2C+Vladimir+N%3BMilanesi%2C+Luciano%3BPavlov%2C+Youri+I&rft.aulast=Rogozin&rft.aufirst=Igor&rft.date=2003-09-01&rft.volume=4&rft.issue=3&rft.spage=210&rft.isbn=&rft.btitle=&rft.title=Briefings+in+bioinformatics&rft.issn=14675463&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-19 N1 - Date created - 2003-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Public health context of women's mental health research. AN - 71287721; 14563109 AB - As more attention is directed to the mental health care of women, sex and gender differences in research design and in regulatory policies have interfaced with clinical care and public policy. An emphasis on women's mental health issues in the provision of treatment and care as well as the design of large-scale screening strategies to identify and treat women with mental disorders promises to be effective public health approaches to reducing the burden of mental illness in women. The past decade has seen increased emphasis on women's mental health and sex/gender differences in the federal sector and in the research community. Federal regulations (summarized in the NIH Outreach Notebook) call for the inclusion of women and minorities in NIH-funded clinical research. The regulations also place emphasis on gender analysis of the results of clinical trials, in particular phase III trials, the findings of which are likely to influence practice. There has been substantial progress toward the goal of including women in research, but more remains to be done. A 2000 GAO report titled "Women's Health: NIH Has Increased Its Efforts to Include Women in Research" commended NIH for tracking the number of women in clinical research but the report also noted that relatively few NIH-funded studies, including major clinical trials, had reported findings by gender of study participants. This was seen as an impediment to progress in developing gender-based effective treatments. In the past decade, the women's health field has moved beyond an exclusive emphasis on women's reproductive function to one that defines health as a scientific enterprise to identify clinically important sex and gender differences in prevalence, etiology, course, and treatment of illnesses affecting men and women in the population as well as conditions specific to women. Nonetheless, for mental disorders, women's reproductive function and its impact on mental health conditions is still understudied. Based on the epidemiology of mental disorders, the course of mental disorders in women in relation to reproductive transitions remains an important issue for the mental health field because the burden of mental disorders, such as depression and anxiety, fall disproportionately on women of childbearing and childrearing age. The public health emphasis on women's mental health does not lessen the basic scientific opportunities to be had by a focus on gender and sex differences. A 2001 report of the Institute of Medicine titled "Exploring the Biological Contributions to Health: Does Sex Matter?" underscores the benefit to health care of looking for sex differences at the biological level. Basic and clinical neuroscience research is rapidly accruing a knowledge base that will provide information at the level of genes and cells of the influences of biological sex on mental health outcomes in both women and men. A focus on women's mental health and gender/sex differences research promises to yield improvement in treatments and services and thereby to improve the public health as well as to increase fundamental knowledge about the etiology and neurophysiology of mental disorders. JF - The Psychiatric clinics of North America AU - Blehar, Mary C AD - National Institute of Mental Health, NIH/DHHS, 6001 Executive Boulevard, Suite 8125, MSC9659, Bethesda, MD 20892, USA. mblehar@mail.nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 781 EP - 799 VL - 26 IS - 3 SN - 0193-953X, 0193-953X KW - Index Medicus KW - Public Sector KW - Evidence-Based Medicine KW - Ethnic Groups KW - Risk Factors KW - Humans KW - Family KW - Mental Health Services KW - Female KW - Substance-Related Disorders -- epidemiology KW - Public Health KW - Mental Disorders -- epidemiology KW - Mental Disorders -- psychology KW - Mental Disorders -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71287721?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Psychiatric+clinics+of+North+America&rft.atitle=Public+health+context+of+women%27s+mental+health+research.&rft.au=Blehar%2C+Mary+C&rft.aulast=Blehar&rft.aufirst=Mary&rft.date=2003-09-01&rft.volume=26&rft.issue=3&rft.spage=781&rft.isbn=&rft.btitle=&rft.title=The+Psychiatric+clinics+of+North+America&rft.issn=0193953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-01 N1 - Date created - 2003-10-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interacting with Cancer Patients: The Significance of Physicians' Communication Behavior AN - 60491648; 200400564 AB - A diagnosis of cancer typically results in patients experiencing uncertainty about, & loss of control over, their situation, which in turn has a negative influence on their health outcomes. Cancer treatment further disrupts patients' quality of life. Throughout their cancer journey, patients often rely on their physicians to provide them with social/interpersonal, informational, & decisional support. A growing body of research shows that physicians' communication behavior does indeed have a positive impact on patient health outcomes. Thus, the patient-physician interaction assumes great significance in the cancer care delivery process. It is encouraging to note that research in this area, largely dominated by studies conducted in primary care, is attracting the attention of cancer researchers. In an attempt to encourage & aid future research on patient-physician communication in cancer care, this paper presents a critical evaluation of existing literature on key elements of physicians' communication behavior (ie, interpersonal communication, information exchange, & facilitation of patient involvement in decision making). Different approaches to assessing physician behavior are discussed followed by a review of key findings linking physician behavior with cancer patient health outcomes. Finally, potential limitations of existing research are highlighted & areas for future research are identified. 1 Table, 29 References. Adapted from the source document. JF - Social Science & Medicine AU - Arora, Neeraj K AD - Outcomes Research Branch, Applied Research Program, Division Cancer Control & Population Sciences, National Cancer Instit, Bethesda, MD aroran@mail.nih.gov Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 791 EP - 806 VL - 57 IS - 5 SN - 0277-9536, 0277-9536 KW - Interpersonal Communication KW - Quality of Life KW - Health KW - Practitioner Patient Relationship KW - Cancer KW - Medical Decision Making KW - article KW - 2045: sociology of health and medicine; sociology of medicine & health care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/60491648?accountid=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=Social+Science+%26+Medicine&rft.atitle=Interacting+with+Cancer+Patients%3A+The+Significance+of+Physicians%27+Communication+Behavior&rft.au=Arora%2C+Neeraj+K&rft.aulast=Arora&rft.aufirst=Neeraj&rft.date=2003-09-01&rft.volume=57&rft.issue=5&rft.spage=791&rft.isbn=&rft.btitle=&rft.title=Social+Science+%26+Medicine&rft.issn=02779536&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Number of references - 129 N1 - Last updated - 2016-09-28 N1 - CODEN - SSCMAW N1 - SubjectsTermNotLitGenreText - Cancer; Practitioner Patient Relationship; Interpersonal Communication; Health; Quality of Life; Medical Decision Making ER - TY - JOUR T1 - Modeling the impacts of child care quality on children's preschool cognitive development AN - 57066906; 245476 AB - The National Institute of Child Health and Human Development (NICHD) Study of Early Child Care compared 3 statistical methods that adjust for family selection bias to test whether child care type and quality relate to cognitive and academic skills. The methods included: multipleregression models of 54-month outcomes, change models of differences in 24- and 54-month outcomes, and residualized change models of 54-month outcomes adjusting for the 24-month outcome. The study was unable to establish empirically which model best adjusted for selection and omitted-variable bias. Nevertheless, results suggested that child care quality predicted cognitive outcomes at 54 months, with effect sizes of.04 to .08 for both infant and preschool ages. Center care during preschool years also predicted outcomes across all models. (Original abstract) JF - Child Development AU - Duncan, Greg J AU - National Institute of Child Health and Human Development Early Child Care Research Network AD - National Institute of Child Health and Human Development Early Child Care Research Network Y1 - 2003/09// PY - 2003 DA - September 2003 SP - 1454 EP - 1475 VL - 74 IS - 5 SN - 0009-3920, 0009-3920 KW - Early life experiences KW - Quality KW - Risk factors KW - Impact analysis KW - Cognitive development KW - Preschool children KW - Child care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57066906?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Modeling+the+impacts+of+child+care+quality+on+children%27s+preschool+cognitive+development&rft.au=Duncan%2C+Greg+J%3BNational+Institute+of+Child+Health+and+Human+Development+Early+Child+Care+Research+Network&rft.aulast=Duncan&rft.aufirst=Greg&rft.date=2003-09-01&rft.volume=74&rft.issue=5&rft.spage=1454&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2003-12-17 N1 - Document feature - refs. tbls. N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Preschool children; Cognitive development; Risk factors; Child care; Early life experiences; Impact analysis; Quality ER - TY - JOUR T1 - Studying the effects of early child care experiences on the development of children of color in the United States: toward a more inclusive research agenda AN - 38531837; 2493059 JF - Child development AU - Johnson, Deborah J AU - Jaeger, Elizabeth AU - Randolph, Suzanne M AU - Cauce, Ana Mari AU - Ward, Janie Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 1227 EP - 1244 VL - 74 IS - 5 SN - 0009-3920, 0009-3920 KW - Sociology KW - Environment KW - Ethnicity KW - Childhood KW - Race KW - Family KW - Ethnic minorities KW - U.S.A. KW - Children KW - Child care KW - Child development KW - Developmental psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/38531837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aibss&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+development&rft.atitle=Studying+the+effects+of+early+child+care+experiences+on+the+development+of+children+of+color+in+the+United+States%3A+toward+a+more+inclusive+research+agenda&rft.au=Johnson%2C+Deborah+J%3BJaeger%2C+Elizabeth%3BRandolph%2C+Suzanne+M%3BCauce%2C+Ana+Mari%3BWard%2C+Janie&rft.aulast=Johnson&rft.aufirst=Deborah&rft.date=2003-09-01&rft.volume=74&rft.issue=5&rft.spage=1227&rft.isbn=&rft.btitle=&rft.title=Child+development&rft.issn=00093920&rft_id=info:doi/ LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - SuppNotes - Evidence is presented of the different cultural and ecological contexts affecting early child care for families of color. It is argued that improvements on previous research require a fundamental shift in how race, ethnicity, and culture as psychological variables are examined. Furthermore, to avoid the pitfalls and failures of previous research, new research must incorporate expanded models of child care and development in childhood. The integrative model of development for children of color proposed by Garcia Coll et al. (1996) is presented as a basis for developing more specific ecological models relevant to addressing child care issues in ethnic minority families. Finally, priority areas for future research are recommended to stimulate and enable child care researchers to adopt a more inclusive view of child care and its effects. N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 3518 10404; 2197 2212 6075 3483; 2192; 2211 652 5676 646 6091 2212; 2212; 4435; 4427 8122; 10555 6091; 4748; 4309; 433 293 14 ER - TY - JOUR T1 - REVIEW: Efficacy of Implantable Cardioverter Defibrillator Therapy for Primary and Secondary Prevention of Sudden Cardiac Death in Hypertrophic Cardiomyopathy AN - 19958439; 6623510 AB - Risk stratification and effectiveness of implantable cardioverter-defibrillator (ICD) therapy are unresolved issues in hypertrophic cardiomyopathy (HCM), a cardiac disease that is associated with arrhythmias and sudden death. We assessed ICD therapy in 132 patients with HCM: age at implantation was34 plus or minus 17 years, and 44 (33%) patients wereaged less than or equal to 20 years. Indications were sustained ventricular tachycardia (VT) or cardiac arrest (secondary prevention) in 47 (36%) patients, and clinical features associated with increased risk for sudden death (primary prevention) in 85 (64%) patients. There were 6 deaths and 55 appropriate interventions in 27 (20%) patients during a mean follow-up period of4.8 plus or minus 4.2 years: 5-year survival and event-free rates were96% plus or minus 2%and75% plus or minus 5%, respectively. ICD intervention-free rates were significantly less for secondary than for primary prevention:64% plus or minus 7%versus84% plus or minus 6%at 5 years,P = 0.02. Notably, 59 of 67 events (cardiac arrest and therapeutic ICD interventions), or 88%, occurred during sedentary or noncompetitive activity. Incidence of therapeutic shocks was related to age but not to other reported risk factors, including severity of cardiac hypertrophy, nonsustained VT during Holter monitoring, and abnormal blood pressure response to exercise. ICD related complications occurred in 38 (29%) patients, including 60 inappropriate ICD interventions in 30 (23%) patients. However, 8 (27%) of the patients with inappropriate shocks also had therapeutic interventions. ICD is effective for secondary prevention of sudden death in HCM. However, selection of patients for primary prevention of sudden death, and prevention of device related complications require further refinement. (PACE 2003; 26:1887-1896) JF - Pacing and Clinical Electrophysiology AU - Begley, David A AU - Mohiddin, Saidi A AU - Tripodi, Dorothy AU - Winkler, Judith B AU - Fananapazir, Lameh AD - Address for reprints: Lameh Fananapazir, MD, FRCP, Cardiovascular Branch, Building 10, Room 7B-15, 10 Center Dr MSC 1650, Bethesda MD 20892-1650, fananapa@nih.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 1887 EP - 1896 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 26 IS - 9 SN - 0147-8389, 0147-8389 KW - Biotechnology and Bioengineering Abstracts KW - Heart KW - Age KW - Arrhythmia KW - Tachycardia KW - Survival KW - Therapeutic applications KW - Electrophysiology KW - Blood pressure KW - Physical training KW - Cardiomyopathy KW - Hypertrophy KW - Shock KW - Risk factors KW - Defibrillators KW - Cardiovascular diseases KW - Heart diseases KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19958439?accountid=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=Pacing+and+Clinical+Electrophysiology&rft.atitle=REVIEW%3A+Efficacy+of+Implantable+Cardioverter+Defibrillator+Therapy+for+Primary+and+Secondary+Prevention+of+Sudden+Cardiac+Death+in+Hypertrophic+Cardiomyopathy&rft.au=Begley%2C+David+A%3BMohiddin%2C+Saidi+A%3BTripodi%2C+Dorothy%3BWinkler%2C+Judith+B%3BFananapazir%2C+Lameh&rft.aulast=Begley&rft.aufirst=David&rft.date=2003-09-01&rft.volume=26&rft.issue=9&rft.spage=1887&rft.isbn=&rft.btitle=&rft.title=Pacing+and+Clinical+Electrophysiology&rft.issn=01478389&rft_id=info:doi/10.1046%2Fj.1460-9592.2003.00285.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-07-01 N1 - SuppNotes - Figures, 2; tables, 4; formulas, 44; references, 49. N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Heart; Arrhythmia; Age; Tachycardia; Therapeutic applications; Survival; Electrophysiology; Blood pressure; Physical training; Cardiomyopathy; Hypertrophy; Shock; Defibrillators; Risk factors; Cardiovascular diseases; Heart diseases DO - http://dx.doi.org/10.1046/j.1460-9592.2003.00285.x ER - TY - JOUR T1 - Review: Taking Possession: Biogenesis of the Salmonella-Containing Vacuole AN - 19289960; 6596701 AB - The Gram-negative pathogen Salmonella enterica can survive and replicate within a variety of mammalian cells. Regardless of the cell type, internalized bacteria survive and replicate within the Salmonella-containing vacuole, the biogenesis of which is dependent on bacterially encoded virulence factors. In particular, Type III secretion systems translocate bacterial effector proteins into the eukaryotic cell where they can specifically interact with a variety of targets. Salmonella has two distinct Type III secretion systems that are believed to have completely different functions. The SPI2 system is induced intracellularly and is required for intracellular survival in macrophages; it plays no role in invasion but is categorized as being required for Salmonella-containing vacuole biogenesis. In contrast, the SPI1 Type III secretion system is induced extracellularly and is essential for invasion of nonphagocytic cells. Its role in post-invasion processes has not been well studied. Recent studies indicate that Salmonella-containing vacuole biogenesis may be more dependent on SPI1 than previously believed. Other non-SPI2 virulence factors and the host cell itself may play critical roles in determining the intracellular environment of this facultative intracellular pathogen. In this review we discuss the recent advances in determining the mechanisms by which Salmonella regulate Salmonella-containing vacuole biogenesis and the implications of these findings. JF - Traffic AU - Knodler, Leigh A AU - Steele-Mortimer, Olivia AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, National Institutes of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840, USA, omortimer@niaid.nih.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 587 EP - 599 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 4 IS - 9 SN - 1398-9219, 1398-9219 KW - Microbiology Abstracts B: Bacteriology KW - Macrophages KW - Cell survival KW - virulence factors KW - Mammalian cells KW - Salmonella enterica KW - Secretion KW - Reviews KW - Vacuoles KW - Pathogens KW - J 02350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19289960?accountid=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=Traffic&rft.atitle=Review%3A+Taking+Possession%3A+Biogenesis+of+the+Salmonella-Containing+Vacuole&rft.au=Knodler%2C+Leigh+A%3BSteele-Mortimer%2C+Olivia&rft.aulast=Knodler&rft.aufirst=Leigh&rft.date=2003-09-01&rft.volume=4&rft.issue=9&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Traffic&rft.issn=13989219&rft_id=info:doi/10.1034%2Fj.1600-0854.2003.00118.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - SuppNotes - Figures, 2; tables, 2; references, 118. N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Cell survival; Macrophages; Mammalian cells; virulence factors; Reviews; Secretion; Vacuoles; Pathogens; Salmonella enterica DO - http://dx.doi.org/10.1034/j.1600-0854.2003.00118.x ER - TY - JOUR T1 - Rate of nasopharyngeal carriage, antimicrobial resistance and serotype of Streptococcus pneumoniae among children in northern Taiwan AN - 19215946; 5779789 AB - Multiple-antibiotic-resistant strains of Streptococcus pneumoniae are isolated from clinical specimens in Taiwan with increasing frequency. This study aimed to define the carriage rate of S. pneumoniae among children in northern Taiwan, and to determine the antibiotic susceptibility and the serotype incidence of these isolates. Nasopharyngeal swabs were taken from a total of 478 children (age, 1 month-14 years) who sought medical care only for non-infectious disease or routine vaccination at our hospital between July 1998 and November 1999. S. pneumoniae was isolated from 95 patients, and the collected isolates were available for analysis. All pneumococcal isolates were serotyped and their antimicrobial susceptibility tested by standard methods. The total rate of pneumococcal carriage in the study population was 19.9% and the isolation rate was higher in children aged between 2 and 5 years. Only 10 (10.5%) of the isolates were susceptible to penicillin (minimum inhibitory concentration [MIC], less than or equal to 0.06 mu g/mL); 47 (49.5%) isolates were intermediately resistant (MIC, 0.12-1 mu g/mL) and 38 (40%) were highly resistant (MIC, greater than or equal to 2 mu g/mL). Among the 95 S. pneumoniae isolates, the common serotypes were 23F (22%), 6B (18.9%), 19F (18.9%), and 14 (8.4%). Evaluation of the results showed that serotypes 23F (24.7%), 19F (21.2%), 6B (15.3%), and 14 (9.4%) composed 70.6% of all penicillin-non-susceptible S. pneumoniae isolates. The significant rate of isolation of penicillin-non-susceptible S. pneumoniae from children indicates that both the judicious use of antibiotics and the availability of conjugate pneumococcal vaccines are the most appropriate strategy to reduce the carriage of resistant pneumococci. JF - Journal of Microbiology, Immunology and Infection AU - Lo, Wen-Tsung AU - Wang, Chih-Chien AU - Yu, Cheing-Mei AU - Chu, Mong-Ling AD - Department of Pediatrics, Tri-Service General Hospital 325, Cheng-Kung Road, Section 2, Nei-Hu, Taipei, Taiwan, 114, ROC, ndmcccw@yahoo.com.tw Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 175 EP - 181 PB - Lippincott Willaims & Wilkins Asia Ltd., Suite 907-910, New T&T Centre, Harbour City 7 Canton Road Tsimshatsui, Kowloon NT Hong Kong, [URL:http://www.lww.com/] VL - 36 IS - 3 SN - 1684-1182, 1684-1182 KW - children KW - Multiple antibiotic resistance KW - Microbiology Abstracts B: Bacteriology KW - Taiwan KW - Streptococcus pneumoniae KW - Serotypes KW - Isolates KW - Disease resistance KW - Swabs KW - Antibiotic resistance KW - Susceptibility KW - Penicillin KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19215946?accountid=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+Microbiology%2C+Immunology+and+Infection&rft.atitle=Rate+of+nasopharyngeal+carriage%2C+antimicrobial+resistance+and+serotype+of+Streptococcus+pneumoniae+among+children+in+northern+Taiwan&rft.au=Lo%2C+Wen-Tsung%3BWang%2C+Chih-Chien%3BYu%2C+Cheing-Mei%3BChu%2C+Mong-Ling&rft.aulast=Lo&rft.aufirst=Wen-Tsung&rft.date=2003-09-01&rft.volume=36&rft.issue=3&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Journal+of+Microbiology%2C+Immunology+and+Infection&rft.issn=16841182&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pneumoniae; Taiwan; Penicillin; Disease resistance; Isolates; Serotypes; Swabs; Susceptibility; Antibiotic resistance ER - TY - JOUR T1 - Activated Clearance of a Biotinylated Macromolecular MRI Contrast Agent from the Blood Pool Using an Avidin Chase AN - 19202103; 5790584 AB - The enhancement characteristics of a contrast agent are dependent on its pharmacokinetics within the body. In the case of macromolecular contrast agents, prolonged enhancement of the blood pool is seen after the first dose, limiting opportunities for repeated injection in the same session. If the enhancement within the blood pool could be intentionally switched off, the macromolecular contrast agents could be used both to define blood volume and vessel permeability, properties that could be useful in studying angiogenesis. In the current study, the avidin-biotin system was coupled to a dendrimer-based macromolecular MRI contrast agent to switch enhancement from the blood pool to the liver. Because avidin causes rapid trapping of the contrast agent in the liver, the blood pool cleared within 2 min of the injection of avidin. This system can be applied to all dendrimer-based macromolecular MRI contrast agents to investigate blood volume and vascular permeability. Moreover, it permits the repeated injection of the contrast agent and the "avidin switch" during a single MR experiment. JF - Bioconjugate Chemistry AU - Kobayashi, Hisataka AU - Kawamoto, Satomi AU - Star, R A AU - Waldmann, T A AU - Brechbiel, M W AU - Choyke, P L AD - Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 1044 EP - 1047 VL - 14 IS - 5 SN - 1043-1802, 1043-1802 KW - avidin KW - biotin KW - contrast agents KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Permeability KW - Blood vessels KW - Magnetic resonance imaging KW - Angiogenesis KW - Pharmacokinetics KW - Vascular system KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19202103?accountid=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=Bioconjugate+Chemistry&rft.atitle=Activated+Clearance+of+a+Biotinylated+Macromolecular+MRI+Contrast+Agent+from+the+Blood+Pool+Using+an+Avidin+Chase&rft.au=Kobayashi%2C+Hisataka%3BKawamoto%2C+Satomi%3BStar%2C+R+A%3BWaldmann%2C+T+A%3BBrechbiel%2C+M+W%3BChoyke%2C+P+L&rft.aulast=Kobayashi&rft.aufirst=Hisataka&rft.date=2003-09-01&rft.volume=14&rft.issue=5&rft.spage=1044&rft.isbn=&rft.btitle=&rft.title=Bioconjugate+Chemistry&rft.issn=10431802&rft_id=info:doi/10.1021%2Fbc034064l LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Pharmacokinetics; Vascular system; Permeability; Blood vessels; Angiogenesis DO - http://dx.doi.org/10.1021/bc034064l ER - TY - JOUR T1 - Quorum-Sensing Control of Biofilm Factors in Staphylococcus epidermidis AN - 18955848; 5746809 AB - Staphylococcus epidermidis is the most frequent cause of nosocomial sepsis and catheter-related infections, in which biofilm formation is considered to be the main virulence mechanism. Quorum-sensing systems have been recognized as important regulators of virulence and biofilm formation in many bacteria. There is a single quorum-sensing system in S. epidermidis encoded by the agr operon. To investigate quorum-sensing control of biofilm formation, we constructed an agr deletion mutant, assayed for the different stages of biofilm formation, and determined agr-dependent regulation of biofilm factors. The agr mutant showed increased biofilm formation, primary attachment, and expression of the autolysin AtlE, but lacked delta -toxin production. However, the level of polysaccharide intercellular adhesin expression was equivalent to the isogenic wild-type strain. In contrast to AtlE, which is known to influence primary attachment, delta -toxin appeared to exert its effect on attachment to polystyrene during later stages of biofilm formation. Importantly, addition of cross-inhibiting pheromones mimicked an agr mutation and significantly enhanced biofilm formation, which suggests that care should be used when treating S. epidermidis infections with cross-inhibiting peptides. Our data demonstrate the importance of quorum sensing in the establishment of a biofilm in this critical human pathogen. JF - Journal of Infectious Diseases AU - Vuong, C AU - Gerke, C AU - Somerville, G A AU - Fischer, E R AU - Otto, M AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA Y1 - 2003/09/01/ PY - 2003 DA - 2003 Sep 01 SP - 706 EP - 718 VL - 188 IS - 5 SN - 0022-1899, 0022-1899 KW - AtlE protein KW - quorum sensing KW - Microbiology Abstracts B: Bacteriology KW - Adhesins KW - Pheromones KW - Nosocomial infection KW - Catheters KW - Biofilms KW - Staphylococcus epidermidis KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18955848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Quorum-Sensing+Control+of+Biofilm+Factors+in+Staphylococcus+epidermidis&rft.au=Vuong%2C+C%3BGerke%2C+C%3BSomerville%2C+G+A%3BFischer%2C+E+R%3BOtto%2C+M&rft.aulast=Vuong&rft.aufirst=C&rft.date=2003-09-01&rft.volume=188&rft.issue=5&rft.spage=706&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Staphylococcus epidermidis; Nosocomial infection; Pheromones; Catheters; Adhesins; Biofilms ER - TY - JOUR T1 - Recombinant Antibodies for the Diagnosis and Treatment of Cancer AN - 18947376; 5731536 AB - The advent of recombinant antibody technology led to an enormous revival in the use of antibodies as diagnostic and therapeutic tools for fighting cancer. This review provides a brief historical sketch of the development of recombinant antibodies for the diagnosis and immunotherapy of cancer and summarizes the most significant clinical data for the best established reagents to date. It also discusses clinically relevant aspects of the use of recombinant antibodies in cancer patients. JF - Molecular Biotechnology AU - Krauss, J AD - SAIC Frederick, National Cancer Institute at Frederick, Bldg. 320, Rm. 8, Frederick, MD 21702-1201, USA, jkrauss@ncifcrf.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 1 EP - 17 VL - 25 IS - 1 SN - 1073-6085, 1073-6085 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Antibodies KW - Immunotherapy KW - Reviews KW - Cancer patients KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W3 33160:Antibody based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18947376?accountid=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=Recombinant+Antibodies+for+the+Diagnosis+and+Treatment+of+Cancer&rft.au=Krauss%2C+J&rft.aulast=Krauss&rft.aufirst=J&rft.date=2003-09-01&rft.volume=25&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Molecular+Biotechnology&rft.issn=10736085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue on Cancer Immunotherapy. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Cancer patients; Antibodies; Immunotherapy ER - TY - JOUR T1 - Preparation and Characterization of Group A Meningococcal Capsular Polysaccharide Conjugates and Evaluation of Their Immunogenicity in Mice AN - 18870566; 5695425 AB - Epidemic and endemic meningitis caused by group A Neisseria meningitidis remains a problem in sub-Saharan Africa. Although group A meningococcal capsular polysaccharide (GAMP) vaccine confers immunity at all ages, the improved immunogenicity of a conjugate and its compatibility with the World Health Organization's Extended Program on Immunization offers advantages over GAMP alone. Conjugates of GAMP bound to bovine serum albumin (BSA) were synthesized, characterized, and evaluated for their immunogenicities in mice. Two methods, involving adipic acid dihydrazide (ADH) as a linker, were used. First, ADH was bound to GAMP activated with cyanogen bromide (CNBr) or with 1-cyano- 4(dimethylamino)-pyridinium tetrafluoroborate (CDAP) to form GAMP sub(CNBr)AH and GAMP sub(CDAP)AH. These derivatives were bound to BSA by 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide (EDC) to form GAMP sub(CNBr)AH-BSA and GAMP sub(CDAP)AH-BSA. Second, ADH was bound to BSA with EDC to form AHBSA. AHBSA was bound to activated GAMP to form GAMP sub(CNBr)-AHBSA and GAMP sub(CDAP)-AHBSA. The yield of GAMP sub(CDAP)-AHBSA (35 to 40%) was higher than those of the other conjugates (5 to 20%). GAMP conjugates elicited immunoglobulin G (IgG) anti-GAMP in all mice after three injections of 2.5 or 5.0 mu g of GAMP: the geometric mean (GM) was highest in recipients of GAMP sub(CDAP)-AHBSA (11.40 enzyme-linked immunosorbent assay units). Although the difference was not statistically significant, the 5.0- mu g dose elicited a higher GM IgG anti-GAMP than the 2.5- mu g dose. Low levels of anti-GAMP were elicited by GAMP alone. GAMP sub(CDAP)-AHBSA elicited bactericidal activity roughly proportional to the level of IgG anti-GAMP. JF - Infection and Immunity AU - Jin, Z AU - Chu, C AU - Robbins, J B AU - Schneerson, R AD - National Institute of Child Health and Development, National Institutes of Health, Building 6, Room 424, Bethesda, MD 20892-2720, jinz@mail.nih.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 5115 EP - 5120 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 71 IS - 9 SN - 0019-9567, 0019-9567 KW - 1-cyano-4(dimethylamino)-pyridinium tetrafluoroborate KW - 1-cyano-4-dimethylaminopyridinium tetrafluoroborate KW - cyanogen bromide KW - mice KW - polysaccharides KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18870566?accountid=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=Preparation+and+Characterization+of+Group+A+Meningococcal+Capsular+Polysaccharide+Conjugates+and+Evaluation+of+Their+Immunogenicity+in+Mice&rft.au=Jin%2C+Z%3BChu%2C+C%3BRobbins%2C+J+B%3BSchneerson%2C+R&rft.aulast=Jin&rft.aufirst=Z&rft.date=2003-09-01&rft.volume=71&rft.issue=9&rft.spage=5115&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.71.9.5115-5120.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.71.9.5115-5120.2003 ER - TY - JOUR T1 - Antimicrobial Characterization of Human beta -Defensin 3 Derivatives AN - 18870040; 5695498 AB - Human beta -defensin 3 (hBD3) is a highly basic 45-amino-acid protein that acts both as an antimicrobial agent and as a chemoattractant molecule. Although the nature of its antimicrobial activity is largely electrostatic, the importance of the molecular structure on this activity is poorly understood. Two isoforms of hBD3 were synthesized: the first with native disulfide linkages and the second with nonnative linkages. In a third synthetic peptide, all cysteine residues were replaced with alpha -aminobutyric acid, creating a completely linear peptide. A series of six small, linear peptides corresponding to regions of hBD3 with net charges ranging from +4 to +8 (at pH 7) and lengths ranging from 9 to 20 amino acids were also synthesized. The linear full-length peptide showed the highest microbicidal activity against Escherichia coli and Staphylococcus aureus, while all three full-length forms showed equal activity against Candida albicans. The linear peptide also showed high activity against Enterococcus faecium and Pseudomonas aeruginosa. Peptides corresponding to the C terminus showed higher activities when tested against E. coli, with the most active peptides being the most basic. However, only the peptide corresponding to the N terminus of hBD3 showed any activity against S. aureus and C. albicans. Further, N-terminal deletion mutants of native hBD3 showed diminished activities against S. aureus. Thus, the antimicrobial properties of hBD3 derivatives are determined by both charge and structure. JF - Antimicrobial Agents & Chemotherapy AU - Hoover, D M AU - Wu, Z AU - Tucker, K AU - Lu, W AU - Lubkowski, J AD - Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, jacek@ncifcrf.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 2804 EP - 2809 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 47 IS - 9 SN - 0066-4804, 0066-4804 KW - BD3 protein KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - J 02855:Human Bacteriology: Others KW - K 03063:Effects of physical & chemical factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18870040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Antimicrobial+Characterization+of+Human+beta+-Defensin+3+Derivatives&rft.au=Hoover%2C+D+M%3BWu%2C+Z%3BTucker%2C+K%3BLu%2C+W%3BLubkowski%2C+J&rft.aulast=Hoover&rft.aufirst=D&rft.date=2003-09-01&rft.volume=47&rft.issue=9&rft.spage=2804&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/10.1128%2FAAC.47.9.2804-2809.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/AAC.47.9.2804-2809.2003 ER - TY - JOUR T1 - Theoretical analysis of mutation hotspots and their DNA sequence context specificity AN - 18862967; 5713936 AB - Mutation frequencies vary significantly along nucleotide sequences such that mutations often concentrate at certain positions called hotspots. Mutation hotspots in DNA reflect intrinsic properties of the mutation process, such as sequence specificity, that manifests itself at the level of interaction between mutagens, DNA, and the action of the repair and replication machineries. The hotspots might also reflect structural and functional features of the respective DNA sequences. When mutations in a gene are identified using a particular experimental system, resulting hotspots could reflect the properties of the gene product and the mutant selection scheme. Analysis of the nucleotide sequence context of hotspots can provide information on the molecular mechanisms of mutagenesis. However, the determinants of mutation frequency and specificity are complex, and there are many analytical methods for their study. Here we review computational approaches for analyzing mutation spectra (distribution of mutations along the target genes) that include many mutable (detectable) positions. The following methods are reviewed: derivation of a consensus sequence, application of regression approaches to correlate nucleotide sequence features with mutation frequency, mutation hotspot prediction, analysis of oligonucleotide composition of regions containing mutations, pairwise comparison of mutation spectra, analysis of multiple spectra, and analysis of 'context-free' characteristics. The advantages and pitfalls of these methods are discussed and illustrated by examples from the literature. The most reliable analyses were obtained when several methods were combined and information from theoretical analysis and experimental observations was considered simultaneously. Simple, robust approaches should be used with small samples of mutations, whereas combinations of simple and complex approaches may be required for large samples. We discuss several well-documented studies where analysis of mutation spectra has substantially contributed to the current understanding of molecular mechanisms of mutagenesis. The nucleotide sequence context of mutational hotspots is a fingerprint of interactions between DNA and DNA repair, replication, and modification enzymes, and the analysis of hotspot context provides evidence of such interactions. JF - Mutation Research-Reviews in Mutation Research AU - Rogozin, IB AU - Pavlov, YI AD - Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russia, pavlov@niehs.nih.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 65 EP - 85 VL - 544 IS - 1 SN - 1383-5742, 1383-5742 KW - Genetics Abstracts; Toxicology Abstracts KW - X 24240:Miscellaneous KW - G 07220:General theory/testing systems UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18862967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Reviews+in+Mutation+Research&rft.atitle=Theoretical+analysis+of+mutation+hotspots+and+their+DNA+sequence+context+specificity&rft.au=Rogozin%2C+IB%3BPavlov%2C+YI&rft.aulast=Rogozin&rft.aufirst=IB&rft.date=2003-09-01&rft.volume=544&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Reviews+in+Mutation+Research&rft.issn=13835742&rft_id=info:doi/10.1016%2FS1383-5742%2803%2900032-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S1383-5742(03)00032-2 ER - TY - JOUR T1 - Genetic Loci for Coaggregation Receptor Polysaccharide Biosynthesis in Streptococcus gordonii 38 AN - 18862448; 5701615 AB - The cell wall polysaccharide of Streptococcus gordonii 38 functions as a coaggregation receptor for surface adhesins on other members of the oral biofilm community. The structure of this receptor polysaccharide (RPS) is defined by a heptasaccharide repeat that includes a GalNAc beta 1-> 3Gal-containing recognition motif. The same RPS has now been identified from S. gordonii AT, a partially sequenced strain. PCR primers designed from sequences in the genomic database of strain AT were used to identify and partially characterize the S. gordonii 38 RPS gene cluster. This cluster includes genes for seven putative glycosyltransferases, a polysaccharide polymerase (Wzy), an oligosaccharide repeating unit transporter (Wzx), and a galactofuranose mutase, the enzyme that promotes synthesis of UDP-Galf, one of five predicted RPS precursors. Genes outside this region were identified for the other four nucleotide-linked sugar precursors of RPS biosynthesis, namely, those for formation of UDP-Glc, UDP-Gal, UDP-GalNAc, and dTDP-Rha. Two genes for putative galactose 4-epimerases were identified. The first, designated galE1, was identified as a pseudogene in the galactose operon, and the second, designated galE2, was transcribed with three of the four genes for dTDP-Rha biosynthesis (i.e., rmlA, rmlC, and rmlB). Insertional inactivation of galE2 abolished (i) RPS production, (ii) growth on galactose, and (iii) both UDP-Gal and UDP-GalNAc 4-epimerase activities in cell extracts. Repair of the galE1 pseudogene in this galE2 mutant restored growth on galactose but not RPS production. Cell extracts containing functional GalE1 but not GalE2 contained UDP-Gal 4-epimerase but not UDP-GalNAc 4-epimerase activity. Thus, provision of both UDP-Gal and UDP-GalNAc for RPS production by S. gordonii 38 depends on the dual specificity of the epimerase encoded by galE2. JF - Journal of Bacteriology AU - Xu, D-Q AU - Thompson, J AU - Cisar, JO AD - Bldg. 30, Rm. 532, 30 Convent Dr., NIDCR, NIH, Bethesda, MD 20892-4352, john.cisar@nih.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 5419 EP - 5430 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 185 IS - 18 SN - 0021-9193, 0021-9193 KW - galE2 gene KW - glycosyltransferase KW - rmlA gene KW - rmlB gene KW - rmlC gene KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Gene expression KW - Streptococcus gordonii KW - UDPglucose 4-epimerase KW - Gene clusters KW - Receptors KW - Biofilms KW - Polysaccharides KW - Loci KW - Cell walls KW - G 07320:Bacterial genetics KW - J 02730:Carbohydrates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18862448?accountid=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=Genetic+Loci+for+Coaggregation+Receptor+Polysaccharide+Biosynthesis+in+Streptococcus+gordonii+38&rft.au=Xu%2C+D-Q%3BThompson%2C+J%3BCisar%2C+JO&rft.aulast=Xu&rft.aufirst=D-Q&rft.date=2003-09-01&rft.volume=185&rft.issue=18&rft.spage=5419&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.185.18.5419-5430.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Gene expression; UDPglucose 4-epimerase; Gene clusters; Receptors; Biofilms; Polysaccharides; Loci; Cell walls; Streptococcus gordonii DO - http://dx.doi.org/10.1128/JB.185.18.5419-5430.2003 ER - TY - JOUR T1 - DNA immunization followed by a single boost with cells: a protein-free immunization protocol for production of monoclonal antibodies against the native form of membrane proteins AN - 18832473; 5754228 AB - Recent advancements in antibody-based therapies require the development of an efficient method for generation of monoclonal antibodies (MAbs) against the native form of membrane proteins. We examined DNA immunization followed by a single boost with cells as a protein-free immunization protocol for production of MAbs. Mice immunized with plasmid cDNAs encoding human CD30 or Ret tyrosine kinase were given a single boost with cells expressing the corresponding antigen prior to cell fusion. A total of nine cell fusion experiments revealed that the cell boost is necessary for efficient generation of hybridomas and the DNA-cell boost method gave good yields of specific MAbs (5-59 MAbs from one mouse). All IgG isotypes except IgG3 were generated, although IgG2a was the dominant isotype. All the MAbs reacted with native antigens expressed on cells in a fluorescence-activated cell sorter (FACS) analysis as well as with recombinant CD30 or Ret protein genetically fused with human Fc in an enzyme-linked immunosorbent assay (ELISA). The affinities of the anti-CD30 MAbs to CD30-Fc protein ranged from 0.9 to 12.4 nM Kds, which were comparable to existing MAbs to these proteins, which range from 3.0 to 13.0 nM. Western blot analysis and topographical epitope mapping experiments based on the mutual competition of pairs of the anti-CD30 MAbs revealed that about 40% of the epitopes were linear epitopes and that each epitope was topographically classified into one of six groups. The large number of MAbs that react with high affinities to a variety of epitopes on the native form of antigens indicates that the method presented in this paper could be generally useful for generating MAbs to other membrane proteins. JF - Journal of Immunological Methods AU - Nagata, S AU - Salvatore, G AU - Pastan, I AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Rm. 5106, Bethesda, MD 20892-4264, USA, pastani@pop.nci.nih.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 59 EP - 72 VL - 280 IS - 1-2 SN - 0022-1759, 0022-1759 KW - man KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - F 06807:Active immunization KW - W3 33240:Immunology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18832473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=DNA+immunization+followed+by+a+single+boost+with+cells%3A+a+protein-free+immunization+protocol+for+production+of+monoclonal+antibodies+against+the+native+form+of+membrane+proteins&rft.au=Nagata%2C+S%3BSalvatore%2C+G%3BPastan%2C+I&rft.aulast=Nagata&rft.aufirst=S&rft.date=2003-09-01&rft.volume=280&rft.issue=1-2&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/10.1016%2FS0022-1759%2803%2900192-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0022-1759(03)00192-3 ER - TY - JOUR T1 - Coinjection with CpG-Containing Immunostimulatory Oligodeoxynucleotides Reduces the Pathogenicity of a Live Vaccine against Cutaneous Leishmaniasis but Maintains Its Potency and Durability AN - 18814128; 5695443 AB - The inoculation of live, nonattenuated Leishmania major to produce a lesion in a selected site that heals, referred to as leishmanization, is to date the only vaccine against leishmaniasis that has proven to be effective in humans. Its use has been restricted or abandoned entirely, however, due to safety concerns. In an attempt to develop a leishmanization protocol that minimizes pathology while maintaining long-term protection, live parasites were coinjected with CpG-containing immunostimulatory oligodeoxynucleotides (CpG ODNs) alone or in combination with whole-cell lysates of heat-killed L. major promastigotes bound to alum (ALM). C57BL/6 mice infected intradermally by using L. major plus CpG ODN with or without ALM developed few or no dermal lesions and showed an early containment of parasite growth, while mice infected with L. major with or without ALM developed sizable dermal lesions that required up to 10 weeks to heal. The CpG ODNs provoked a transient inflammation that included an early recruitment and accumulation of gamma interferon- producing CD4 super(+) lymphocytes in the site. Attenuation of the live vaccine did not compromise its ability to confer long-term immunity, as mice receiving L. major and CpG ODN plus ALM were totally protected against reinfection with L. major for up to 6 months. By comparison, the immunity elicited by two efficient nonlive vaccines began to wane by 6 months. Our results suggest that immune modulation using CpG ODNs might be a practical approach to improving the safety of a highly effective live vaccine that has already been widely applied. JF - Infection and Immunity AU - Mendez, S AU - Tabbara, K AU - Belkaid, Y AU - Bertholet, S AU - Verthelyi, D AU - Klinman, D AU - Seder, R A AU - Sacks, D L AD - NIAID, Laboratory of Parasitic Diseases, Bldg. 4, Rm. 126, Center Dr. MSC 0425, Bethesda, MD 20892-0425, dsacks@nih.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 5121 EP - 5129 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 71 IS - 9 SN - 0019-9567, 0019-9567 KW - C57BL/6 mice KW - safety KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biochemistry Abstracts 2: Nucleic Acids KW - K 03086:Immunology & vaccination KW - F 06807:Active immunization KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews KW - N 14800:Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18814128?accountid=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=Infection+and+Immunity&rft.atitle=Coinjection+with+CpG-Containing+Immunostimulatory+Oligodeoxynucleotides+Reduces+the+Pathogenicity+of+a+Live+Vaccine+against+Cutaneous+Leishmaniasis+but+Maintains+Its+Potency+and+Durability&rft.au=Mendez%2C+S%3BTabbara%2C+K%3BBelkaid%2C+Y%3BBertholet%2C+S%3BVerthelyi%2C+D%3BKlinman%2C+D%3BSeder%2C+R+A%3BSacks%2C+D+L&rft.aulast=Mendez&rft.aufirst=S&rft.date=2003-09-01&rft.volume=71&rft.issue=9&rft.spage=5121&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.71.9.5121-5129.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.71.9.5121-5129.2003 ER - TY - JOUR T1 - Nonoperative Management of Functional Hallux Limitus in a Patient With Rheumatoid Arthritis AN - 17970010; 5912398 AB - Background and Purpose. Functional hallux limitus (FHL) is a condition that affects motion at the first metatarsophalangeal joint and may lead to abnormal forefoot plantar pressures, pain, and difficulty with ambulation. The purpose of this case report is to describe a patient with rheumatoid arthritis (RA) and FHL who was managed with foot orthoses, footwear, shoe modifications, and patient education. Case Description. The patient was a 55-year-old woman diagnosed with seropositive RA 10 years previously. Her chief complaint was bilateral foot pain, particularly under the left great toe. Her foot pain had been present for several years, but during the past 5 months it had intensified and interfered with her work performance, activities of daily living, and social life. Outcomes. Following 4 sessions of physical therapy over a 6-week time period, the patient reported complete relief of forefoot pain despite no change in medication use or RA disease pathophysiology. She was able to continuously walk for up to 4 hours. Left hallux peak plantar pressures were reduced from 43 N/cm super(2) to 18 N/cm super(2) with the foot orthoses. Discussion. Patients with RA who develop FHL may benefit from physical therapist management using semirigid foot orthoses, footwear, shoe modifications, and patient education. JF - Physical Therapy AU - Shrader, JA AU - Siegel, K L AD - Department of Rehabilitation Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Department of Health and Human Services, 10 Center Dr, Bethesda, MD 20892-1604, USA, joseph_shrader@nih.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 831 EP - 843 PB - American Physical Therapy Association VL - 83 IS - 9 SN - 0031-9023, 0031-9023 KW - Physical Education Index KW - Feet KW - Physical therapy KW - Arthritis KW - Social behavior KW - Shoes KW - Joints KW - PE 110:Physical Therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17970010?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Physical+Therapy&rft.atitle=Nonoperative+Management+of+Functional+Hallux+Limitus+in+a+Patient+With+Rheumatoid+Arthritis&rft.au=Shrader%2C+JA%3BSiegel%2C+K+L&rft.aulast=Shrader&rft.aufirst=JA&rft.date=2003-09-01&rft.volume=83&rft.issue=9&rft.spage=831&rft.isbn=&rft.btitle=&rft.title=Physical+Therapy&rft.issn=00319023&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Physical therapy; Arthritis; Shoes; Feet; Joints; Social behavior ER - TY - JOUR T1 - Tick-borne Relapsing Fever Caused by Borrelia hermsii, Montana AN - 17562267; 6422607 AB - Five persons contracted tick-borne relapsing fever after staying in a cabin in western Montana. Borrelia hermsii was isolated from the blood of two patients, and Ornithodoros hermsi ticks were collected from the cabin, the first demonstration of this bacterium and tick in Montana. Relapsing fever should be considered when patients who reside or have vacationed in western Montana exhibit a recurring febrile illness. JF - Emerging Infectious Diseases AU - Schwan, T G AU - Policastro, P F AU - Miller, Z AU - Thompson, R L AU - Damrow, T AU - Keirans, JE AD - Rocky Mountain Laboratories, National Institutes of Health, Hamilton, Montana, USA Y1 - 2003/09// PY - 2003 DA - Sep 2003 VL - 9 IS - 9 SN - 1080-6040, 1080-6040 KW - tick-borne relapsing fever KW - Microbiology Abstracts B: Bacteriology KW - Blood KW - Borrelia hermsii KW - Ornithodoros hermsi KW - USA, Montana KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17562267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Emerging+Infectious+Diseases&rft.atitle=Tick-borne+Relapsing+Fever+Caused+by+Borrelia+hermsii%2C+Montana&rft.au=Schwan%2C+T+G%3BPolicastro%2C+P+F%3BMiller%2C+Z%3BThompson%2C+R+L%3BDamrow%2C+T%3BKeirans%2C+JE&rft.aulast=Schwan&rft.aufirst=T&rft.date=2003-09-01&rft.volume=9&rft.issue=9&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Emerging+Infectious+Diseases&rft.issn=10806040&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia hermsii; Ornithodoros hermsi; USA, Montana; Blood ER - TY - JOUR T1 - Evaluation of New Multimedia Formats for Cancer Communications AN - 17426396; 6538910 AB - Background: Providing quality, current cancer information to cancer patients and their families is a key function of the National Cancer Institute (NCI) Web site. This information is now provided in predominantly-text format, but could be provided in formats using multimedia, including animation and sound. Since users have many choices about where to get their information, it is important to provide the information in a format that is helpful and that they prefer. Objective: To pilot and evaluate multimedia strategies for future cancer-information program formats for lay users, the National Cancer Institute created new multimedia versions of existing text programs. We sought to evaluate user performance and preference on these 3 new formats and on the 2 existing text formats. Methods: The National Cancer Institute's "What You Need to Know About Lung Cancer" program was the test vehicle. There were 5 testing sessions, 1 dedicated to each format. Each session lasted about 1 hour, with 9 participants per session and 45 users overall. Users were exposed to the assigned cancer program from beginning to end in 1 of 5 formats: text paperback booklet, paperback booklet formatted in HTML on the Web, spoken audio alone, spoken audio synchronized with a text Web page, and Flash multimedia (animation, spoken audio, and text). Immediately thereafter, the features and design of the 4 alternative formats were demonstrated in detail. A multiple-choice pre-test and post-test quiz on the cancer content was used to assess user learning (performance) before and after experiencing the assigned program. The quiz was administered using an Authorware software interface writing to an Access database. Users were asked to rank from 1 to 5 their preference for the 5 program formats, and provide structured and open-ended comments about usability of the 5 formats. Results: Significant improvement in scores from pre-test to post-test was seen for the total study population. Average scores for users in each of the 5 format groups improved significantly. Increments in improvement, however, were not statistically different between any of the format groups. Significant improvements in quiz scores were seen irrespective of age group or education level. Of the users, 71.1% ranked the Flash program first among the 5 formats, and 84.4% rated Flash as their first or second choice. Audio was the least-preferred format, ranking fifth among 46.7% of users and first among none. Flash was ranked first among users regardless of education level, age group, or format group to which the user was assigned. Conclusions: Under the pilot study conditions, users overwhelmingly preferred the Flash format to the other 4 formats. Learning occurred equally in all formats. Use of multimedia should be considered as communication strategies are developed for updating cancer content and attracting new users. JF - Journal of Medical Internet Research AU - Bader, J L AU - Strickman-Stein, N AD - Communication Technologies Branch, National Cancer Institute, 6116 Executive Blvd. Suite 3048A, Bethesda MD 20852, USA, jbader@mail.nih.gov Y1 - 2003/09// PY - 2003 DA - Sep 2003 VL - 5 IS - 3 SN - 1438-8871, 1438-8871 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Databases KW - Computer programs KW - software KW - Learning KW - Communication KW - Population studies KW - Cancer KW - Internet KW - Lung cancer KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17426396?accountid=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+Medical+Internet+Research&rft.atitle=Evaluation+of+New+Multimedia+Formats+for+Cancer+Communications&rft.au=Bader%2C+J+L%3BStrickman-Stein%2C+N&rft.aulast=Bader&rft.aufirst=J&rft.date=2003-09-01&rft.volume=5&rft.issue=3&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medical+Internet+Research&rft.issn=14388871&rft_id=info:doi/10.2196%2Fjmir.5.3.e16 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Computer programs; Learning; Communication; Lung cancer; Internet; Databases; Cancer; Population studies; software DO - http://dx.doi.org/10.2196/jmir.5.3.e16 ER - TY - JOUR T1 - Using DNA microarrays for diagnostic and prognostic prediction AN - 1257719449; 16579482 AB - DNA microarrays are a potentially powerful technology for improving diagnostic classification, treatment selection and prognostic assessment. There are, however, many potential pitfalls in the use of microarrays that result in false leads and erroneous conclusions. Effective use of this technology requires new levels of interdisciplinary collaboration with statistical and computational scientists. This paper provides a review of the key features to be observed in developing diagnostic and prognostic classification systems based upon gene expression profiling. It also attempts to outline some of the steps needed to develop initial microarray research findings into classification systems suitable for broad clinical application. JF - Expert Review of Molecular Diagnostics AU - Simon, Richard AD - Biometric Research Branch, Division of Cancer Treatment, and Diagnosis, National Cancer Institute, 9000 Rockville Pike, MSC #7434, Bethesda MD 20892, USA. Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 587 EP - 595 PB - Future Science Group (FSG), Unitec House, 2 Albert Place London N3 1QB United Kingdom VL - 3 IS - 5 SN - 1473-7159, 1473-7159 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Classification KW - Classification systems KW - Computer applications KW - DNA microarrays KW - Gene expression KW - Reviews KW - Statistics KW - Therapeutic applications KW - W 30910:Imaging KW - N 14810:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1257719449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Expert+Review+of+Molecular+Diagnostics&rft.atitle=Using+DNA+microarrays+for+diagnostic+and+prognostic+prediction&rft.au=Simon%2C+Richard&rft.aulast=Simon&rft.aufirst=Richard&rft.date=2003-09-01&rft.volume=3&rft.issue=5&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Expert+Review+of+Molecular+Diagnostics&rft.issn=14737159&rft_id=info:doi/10.1586%2F14737159.3.5.587 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-12-01 N1 - Last updated - 2013-02-22 N1 - SubjectsTermNotLitGenreText - Gene expression; Classification systems; Statistics; Classification; Reviews; Therapeutic applications; Computer applications; DNA microarrays DO - http://dx.doi.org/10.1586/14737159.3.5.587 ER - TY - JOUR T1 - Methadone and Metabolite Urine Concentrations in Patients Maintained on Methadone AN - 1093466908; 17185785 AB - As regulatory control over methadone maintenance relaxes, the need for methods of monitoring compliance will increase. In community clinics, monitoring would most likely involve immunoassays of outpatients' trough urine specimens. There are no published norms for such data. Therefore, we determined concentrations of methadone in 1093 urine specimens collected thrice weekly in 27 outpatients during up to 17 weeks of observed methadone ingestion (35 to 80 mg/day) using a semiquantitative homogeneous enzyme immunoassay (CEDIA). We used a separate CEDIA assay to measure methadone's main metabolite, 2-ethylidene-3,3-diphenylpyrrolidine (EDDP), which may help detect compliance in fast metabolizers or patients who adulterate samples to simulate compliance. Methadone concentrations were more variable than those of EDDP. Concentrations of methadone were < 100 ng/mL in one specimen, between 100 and 300 ng/mL in 27, and 300 ng/mL in all others. EDPP concentrations were 100 ng/mL in all specimens, suggesting that EDDP should be detectable in urine from compliant patients. Methadone and EDDP concentrations significantly increased with methadone dose and (in one participant with poor clinic attendance) significantly decreased following missed methadone doses. Nevertheless, variability was too great to permit estimation of methadone dose (or detect a single missed administration) from any single specimen. JF - Journal of Analytical Toxicology AU - K L, Preston AU - D H, Epstein AU - D, Davoudzadeh AU - M A, Huestis AD - Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224 Y1 - 2003/09// PY - 2003 DA - Sep 2003 SP - 332 EP - 341 PB - Preston Publications, Inc., 6600 W. Touhy Ave. Niles IL 60714 United States VL - 27 IS - 6 SN - 0146-4760, 0146-4760 KW - Toxicology Abstracts KW - Data processing KW - Enzyme immunoassay KW - Metabolites KW - Methadone KW - Urine KW - X 24310:Pharmaceuticals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1093466908?accountid=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=Methadone+and+Metabolite+Urine+Concentrations+in+Patients+Maintained+on+Methadone&rft.au=K+L%2C+Preston%3BD+H%2C+Epstein%3BD%2C+Davoudzadeh%3BM+A%2C+Huestis&rft.aulast=K+L&rft.aufirst=Preston&rft.date=2003-09-01&rft.volume=27&rft.issue=6&rft.spage=332&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ L2 - http://www.ingentaconnect.com/content/oup/jat/2003/00000027/00000006/art00002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-10-01 N1 - Last updated - 2012-10-19 N1 - SubjectsTermNotLitGenreText - Methadone; Data processing; Urine; Metabolites; Enzyme immunoassay ER - TY - JOUR T1 - Stimulation of Kv1.3 potassium channels by death receptors during apoptosis in Jurkat T lymphocytes. AN - 73595178; 12807917 AB - The loss of intracellular potassium is a pivotal step in the induction of apoptosis but the mechanisms underlying this response are poorly understood. Here we report caspase-dependent stimulation of potassium channels by the Fas receptor in a human Jurkat T cell line. Receptor activation with Fas ligand for 30 min increased the amplitude of voltage-activated potassium currents 2-fold on average. This produces a sustained outward current, approximately 10 pA, at physiological membrane potentials during Fas ligand-induced apoptosis. Both basal and Fas ligand-induced currents were blocked completely by toxins that selectively inhibit Kv1.3 potassium channels. Kv1.3 stimulation required the expression of Fas-associated death domain protein and activation of caspase 8, but did not require activation of caspase 3 or protein synthesis. Furthermore, Kv1.3 stimulation by Fas ligand was prevented by chronic stimulation of protein kinase C with 20 nm phorbol 12-myristate 13-acetate during Fas ligand treatment, which also blocks apoptosis. Thus, Fas ligand increases Kv1.3 channel activity through the same canonical apoptotic signaling cascade that is required for potassium efflux, cell shrinkage, and apoptosis. JF - The Journal of biological chemistry AU - Storey, Nina M AU - Gómez-Angelats, Mireia AU - Bortner, Carl D AU - Armstrong, David L AU - Cidlowski, John A AD - Membrane Signaling Group, Laboratory of Signal Transduction, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/08/29/ PY - 2003 DA - 2003 Aug 29 SP - 33319 EP - 33326 VL - 278 IS - 35 SN - 0021-9258, 0021-9258 KW - Arabidopsis Proteins KW - 0 KW - Enzyme Inhibitors KW - FASLG protein, human KW - Fas Ligand Protein KW - Ions KW - KCNA3 protein, human KW - Kv1.3 Potassium Channel KW - Membrane Glycoproteins KW - Potassium Channels KW - Potassium Channels, Voltage-Gated KW - Propidium KW - 36015-30-2 KW - Fatty Acid Desaturases KW - EC 1.14.19.- KW - Fad7 protein, Arabidopsis KW - EC 1.14.99.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - CASP3 protein, human KW - EC 3.4.22.- KW - CASP8 protein, human KW - CASP9 protein, human KW - Caspase 3 KW - Caspase 8 KW - Caspase 9 KW - Caspases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Enzyme Activation KW - Humans KW - Fatty Acid Desaturases -- metabolism KW - Jurkat Cells KW - Cell Separation KW - Electrophysiology KW - Potassium -- metabolism KW - Caspases -- metabolism KW - Protein Kinase C -- metabolism KW - Blotting, Western KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Membrane Potentials KW - Enzyme Inhibitors -- pharmacology KW - Flow Cytometry KW - Propidium -- pharmacology KW - Protein Structure, Tertiary KW - Time Factors KW - Signal Transduction KW - Membrane Glycoproteins -- metabolism KW - Potassium Channels -- metabolism KW - Potassium Channels -- chemistry KW - Apoptosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73595178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Stimulation+of+Kv1.3+potassium+channels+by+death+receptors+during+apoptosis+in+Jurkat+T+lymphocytes.&rft.au=Storey%2C+Nina+M%3BG%C3%B3mez-Angelats%2C+Mireia%3BBortner%2C+Carl+D%3BArmstrong%2C+David+L%3BCidlowski%2C+John+A&rft.aulast=Storey&rft.aufirst=Nina&rft.date=2003-08-29&rft.volume=278&rft.issue=35&rft.spage=33319&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 - 2003-10-02 N1 - Date created - 2003-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - D1 ring is stable and nucleotide-independent, whereas D2 ring undergoes major conformational changes during the ATPase cycle of p97-VCP. AN - 73584897; 12807884 AB - The 97-kDa valosin-containing protein (p97-VCP) belongs to the AAA (ATPases associated with various cellular activities) family and acts as a molecular chaperone in diverse cellular events, including ubiquitinproteasome-mediated degradation. We previously showed that VCP contains a substrate-binding domain, N, and two conserved ATPase domains, D1 and D2, of which D2 is responsible for the major enzyme activity. VCP has a barrel-like structure containing two stacked homo-hexameric rings made of the D1 and D2 domains, and this structure is essential for its biological functions. During ATPase cycles, VCP undergoes conformational changes that presumably apply tensions to the bound substrate, leading to the disassembly of protein complexes or unfolding of the substrate. How ATPase activity is coupled with the conformational changes in VCP complex and the D1 and D2 rings is not clear. In this report, we took biochemical approaches to study the structure of VCP in different nucleotide conditions to depict the conformational changes in the ATPase cycles. In contrast to many AAA chaperones that require ATP/ADP to form oligomers, both wild type VCP and ATP-binding site mutants can form hexamers without the addition of nucleotide. This nucleotide-independent hexamerization requires an intact D1 and the down-stream linker sequence of VCP. Tryptophan fluorescence and trypsin digestion analyses showed that ATP/ADP binding induces dramatic conformational changes in VCP. These changes do not require the presence of an intact ATP-binding site in D1 and is thus mainly attributed to the D2 domain. We propose a model whereby D1, although undergoing minor conformational changes, remains as a relatively trypsin-resistant hexameric ring throughout the ATPase cycle, whereas D2 only does so when it binds to ATP or ADP. After ADP is released at the end of the ATP hydrolysis, D2 ring is destabilized and adopts a relatively flexible and open structure. JF - The Journal of biological chemistry AU - Wang, Qing AU - Song, Changcheng AU - Yang, Xiaoyi AU - Li, Chou-Chi H AD - Basic Research Laboratory, Science Applications International Corporation Frederick, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA. Y1 - 2003/08/29/ PY - 2003 DA - 2003 Aug 29 SP - 32784 EP - 32793 VL - 278 IS - 35 SN - 0021-9258, 0021-9258 KW - Cell Cycle Proteins KW - 0 KW - Molecular Chaperones KW - Nucleotides KW - Recombinant Fusion Proteins KW - Adenosine Diphosphate KW - 61D2G4IYVH KW - Tryptophan KW - 8DUH1N11BX KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - CDC48 protein KW - Index Medicus KW - Nucleotides -- genetics KW - Spectrometry, Fluorescence KW - Molecular Chaperones -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Tryptophan -- chemistry KW - Hydrolysis KW - Models, Biological KW - Chromatography, High Pressure Liquid KW - Binding Sites KW - Cloning, Molecular KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Chromatography, Gel KW - Models, Genetic KW - Adenosine Triphosphate -- metabolism KW - Protein Structure, Tertiary KW - Time Factors KW - Mutation KW - Protein Conformation KW - Adenosine Diphosphate -- metabolism KW - Cell Cycle Proteins -- physiology KW - Cell Cycle Proteins -- chemistry KW - Cell Cycle Proteins -- genetics KW - Adenosine Triphosphatases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73584897?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=D1+ring+is+stable+and+nucleotide-independent%2C+whereas+D2+ring+undergoes+major+conformational+changes+during+the+ATPase+cycle+of+p97-VCP.&rft.au=Wang%2C+Qing%3BSong%2C+Changcheng%3BYang%2C+Xiaoyi%3BLi%2C+Chou-Chi+H&rft.aulast=Wang&rft.aufirst=Qing&rft.date=2003-08-29&rft.volume=278&rft.issue=35&rft.spage=32784&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 - 2003-10-02 N1 - Date created - 2003-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of tryptophan 314 in the conformational changes of beta1,4-galactosyltransferase-I. AN - 73573880; 12927542 AB - beta1,4-Galactosyltransferase-I (beta4Gal-T1) undergoes critical conformational changes upon substrate binding from an open conformation (conf-I) to the closed conformation (conf-II). This change involves two flexible loops: the small (residues 313-316) and the long loop (residues 345-365). Upon substrate binding, Trp314 in the small flexible loop moves towards the catalytic pocket and interacts with the donor and the acceptor substrates. For a better understanding of the role played by Trp314 in the conformational changes of beta4Gal-T1, we mutated it to Ala and carried out substrate-binding, proteolytic and crystallographic studies. The W314A mutation reduces the enzymatic activity, binding to substrates and to the modifier protein, alpha-lactalbumin (LA), by over 99%. The limited proteolysis with Glu-C or Lys-C proteases shows differences in the rate of cleavage of the long loop of the wild-type and mutant W314A, indicating conformational differences in the region between the two proteins. Without substrate, the mutant crystallizes in a conformation (conf-I') (1.9A resolution crystal structure), that is not identical with, but close to an open conformation (conf-I), whereas its complex with the substrates and alpha-lactalbumin, crystallizes in a conformation (2.3A resolution crystal structure) that is identical with the closed conformation (conf-II). This study shows the crucial role Trp314 plays in the conformational state of the long loop, in the binding of substrates and in the catalytic mechanism of the enzyme. JF - Journal of molecular biology AU - Ramasamy, Velavan AU - Ramakrishnan, Boopathy AU - Boeggeman, Elizabeth AU - Qasba, Pradman K AD - Structural Glycobiology Section, LECB, CCR, NCI-Frederick, Building 469, Room 221, 21702, Frederick, MD, USA. Y1 - 2003/08/29/ PY - 2003 DA - 2003 Aug 29 SP - 1065 EP - 1076 VL - 331 IS - 5 SN - 0022-2836, 0022-2836 KW - Macromolecular Substances KW - 0 KW - Recombinant Proteins KW - Manganese KW - 42Z2K6ZL8P KW - Uridine Diphosphate KW - 58-98-0 KW - Tryptophan KW - 8DUH1N11BX KW - Lactalbumin KW - 9013-90-5 KW - Galactosyltransferases KW - EC 2.4.1.- KW - beta-1,4-galactosyltransferase I KW - Acetylglucosamine KW - V956696549 KW - Index Medicus KW - Animals KW - Lactalbumin -- metabolism KW - Manganese -- metabolism KW - Models, Molecular KW - Acetylglucosamine -- metabolism KW - Uridine Diphosphate -- metabolism KW - Recombinant Proteins -- genetics KW - Chromatography, Affinity KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - In Vitro Techniques KW - Catalytic Domain -- genetics KW - Crystallography, X-Ray KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Protein Conformation KW - Galactosyltransferases -- metabolism KW - Galactosyltransferases -- genetics KW - Tryptophan -- chemistry KW - Galactosyltransferases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73573880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=The+role+of+tryptophan+314+in+the+conformational+changes+of+beta1%2C4-galactosyltransferase-I.&rft.au=Ramasamy%2C+Velavan%3BRamakrishnan%2C+Boopathy%3BBoeggeman%2C+Elizabeth%3BQasba%2C+Pradman+K&rft.aulast=Ramasamy&rft.aufirst=Velavan&rft.date=2003-08-29&rft.volume=331&rft.issue=5&rft.spage=1065&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-01 N1 - Date created - 2003-08-20 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1PZT; PDB; 1PZY N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Replication of a cis-syn thymine dimer at atomic resolution AN - 18811918; 5704432 AB - Ultraviolet light damages DNA by catalysing covalent bond formation between adjacent pyrimidines, generating cis-syn cyclobutane pyrimidine dimers (CPDs) as the most common lesion. CPDs block DNA replication by high-fidelity DNA polymerases, but they can be efficiently bypassed by the Y-family DNA polymerase pol eta . Mutations in POLH encoding pol eta are implicated in nearly 20% of xeroderma pigmentosum, a human disease characterized by extreme sensitivity to sunlight and predisposition to skin cancer. Here we have determined two crystal structures of Dpo4, an archaeal pol eta homologue, complexed with CPD-containing DNA, where the 3' and 5' thymine of the CPD separately serves as a templating base. The 3' thymine of the CPD forms a Watson-Crick base pair with the incoming dideoxyATP, but the 5' thymine forms a Hoogsteen base pair with the dideoxyATP in syn conformation. Dpo4 retains a similar tertiary structure, but each unusual DNA structure is individually fitted into the active site for catalysis. A model of the pol eta -CPD complex built from the crystal structures of Saccharomyces cerevisiae apo-pol eta and the Dpo4-CPD complex suggests unique features that allow pol eta to efficiently bypass CPDs. JF - Nature AU - Ling, H AU - Boudsocq, F AU - Plosky, B S AU - Woodgate, R AU - Yang, W AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, and Y1 - 2003/08/28/ PY - 2003 DA - 2003 Aug 28 SP - 1083 EP - 1087 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 424 IS - 6952 SN - 0028-0836, 0028-0836 KW - Dpo4 protein KW - skin cancer KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18811918?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Replication+of+a+cis-syn+thymine+dimer+at+atomic+resolution&rft.au=Ling%2C+H%3BBoudsocq%2C+F%3BPlosky%2C+B+S%3BWoodgate%2C+R%3BYang%2C+W&rft.aulast=Ling&rft.aufirst=H&rft.date=2003-08-28&rft.volume=424&rft.issue=6952&rft.spage=1083&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2Fnature01919 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/nature01919 ER - TY - JOUR T1 - Diadenosine tetraphosphate protects against injuries induced by ischemia and 6-hydroxydopamine in rat brain. AN - 73600058; 12944527 AB - Diadenosine tetraphosphate (AP4A), an endogenous diadenosine polyphosphate, reduces ischemic injury in the heart. In this study, we report the potent and protective effects of AP4A in rodent models of stroke and Parkinson's disease. AP4A, given intracerebroventricularly before middle cerebral artery (MCA) ligation, reduced cerebral infarction size and enhanced locomotor activity in adult rats. The intravenous administration of AP4A also induced protection when given early after MCA ligation. AP4A suppressed terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) induced by hypoxia/reperfusion in primary cortical cultures, and reduced both ischemia-induced translocation of mitochondrial cytochrome c and the increase in cytoplasmic caspase-3 activity in vivo. The purinergic P2/P4 antagonist di-inosine pentaphosphate or P1-receptor antagonist sulfonylphenyl theophylline, but not the P2-receptor antagonist suramin, antagonized the effect of AP4A, suggesting that the observed protection is mediated through an anti-apoptotic mechanism and the activation of P1- and P4-purinergic receptors. AP4A also afforded protection from toxicity induced by unilateral medial forebrain bundle injection of 6-hydroxydopamine (6-OHDA). One month after lesioning, vehicle-treated rats exhibited amphetamine-induced rotation. Minimal tyrosine hydroxylase immunoreactivity was detected in the lesioned nigra or striatum. No KCl-induced dopamine release was found in the lesioned striatum. All of these indices of dopaminergic degeneration were attenuated by pretreatment with AP4A. In addition, AP4A reduced TUNEL in the lesioned nigra 2 d after 6-OHDA administration. Collectively, our data suggest that AP4A is protective against neuronal injuries induced by ischemia or 6-OHDA through the inhibition of apoptosis. We propose that AP4A may be a potentially useful target molecule in the therapy of stroke and Parkinson's disease. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Wang, Yun AU - Chang, Chen-Fu AU - Morales, Marisela AU - Chiang, Yung-Hsiao AU - Harvey, Brandon K AU - Su, Tsung-Ping AU - Tsao, Li-I AU - Chen, Suyu AU - Thiemermann, Christoph AD - National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. ywang@intra.nida.nih.gov Y1 - 2003/08/27/ PY - 2003 DA - 2003 Aug 27 SP - 7958 EP - 7965 VL - 23 IS - 21 KW - Dinucleoside Phosphates KW - 0 KW - Neuroprotective Agents KW - Receptors, Purinergic KW - diadenosine tetraphosphate KW - 5542-28-9 KW - Oxidopamine KW - 8HW4YBZ748 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Apoptosis KW - Blood Pressure KW - Neurons -- drug effects KW - Cerebral Infarction -- prevention & control KW - Dopamine -- metabolism KW - Stroke -- physiopathology KW - Cell Hypoxia KW - Regional Blood Flow KW - Receptors, Purinergic -- metabolism KW - Rats KW - Cerebral Cortex -- blood supply KW - Hypokinesia -- prevention & control KW - Cells, Cultured KW - Locomotion KW - Neurons -- cytology KW - Parkinson Disease, Secondary -- chemically induced KW - Parkinson Disease, Secondary -- pathology KW - Brain Ischemia -- pathology KW - Brain Ischemia -- prevention & control KW - Dinucleoside Phosphates -- therapeutic use KW - Parkinson Disease, Secondary -- prevention & control KW - Neuroprotective Agents -- therapeutic use KW - Brain Ischemia -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73600058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Diadenosine+tetraphosphate+protects+against+injuries+induced+by+ischemia+and+6-hydroxydopamine+in+rat+brain.&rft.au=Wang%2C+Yun%3BChang%2C+Chen-Fu%3BMorales%2C+Marisela%3BChiang%2C+Yung-Hsiao%3BHarvey%2C+Brandon+K%3BSu%2C+Tsung-Ping%3BTsao%2C+Li-I%3BChen%2C+Suyu%3BThiemermann%2C+Christoph&rft.aulast=Wang&rft.aufirst=Yun&rft.date=2003-08-27&rft.volume=23&rft.issue=21&rft.spage=7958&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-16 N1 - Date created - 2003-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Concise and enantioselective synthesis of Fmoc-Pmp(But)2-OH and design of potent Pmp-containing Grb2-SH2 domain antagonists. AN - 73564383; 12916990 AB - [reaction: see text] L-Phosphonomethylphenylalanine (L-Pmp) is an important phosphatase-resistant pTyr analogue. A most concise and stereoselective approach to the synthesis of the suitably protected Fmoc-Pmp(Bu(t))(2)-OH was developed in order to incorporate the functionally significant L-Pmp residue into peptides and peptidomimetics efficiently using standard Fmoc protocol. With this key building block, we are able to efficiently synthesize a series of potent Pmp-containing Grb2-SH2 domain antagonists, which can be used as chemotherapeutic leads for the treatment of erbB2-overexpressed breast cancer. JF - Organic letters AU - Li, Peng AU - Zhang, Manchao AU - Peach, Megan L AU - Liu, Hongpeng AU - Yang, Dajun AU - Roller, Peter P AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA. Y1 - 2003/08/21/ PY - 2003 DA - 2003 Aug 21 SP - 3095 EP - 3098 VL - 5 IS - 17 SN - 1523-7060, 1523-7060 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Amino Acids KW - Fluorenes KW - GRB2 Adaptor Protein KW - Grb2 protein, mouse KW - N(alpha)-fluorenylmethyloxycarbonylamino acids KW - Peptides, Cyclic KW - Proteins KW - 4-phosphonomethylphenylalanine KW - 142434-81-9 KW - Phosphotyrosine KW - 21820-51-9 KW - Phenylalanine KW - 47E5O17Y3R KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Phosphotyrosine -- analogs & derivatives KW - Animals KW - Stereoisomerism KW - Receptor, ErbB-2 -- metabolism KW - Receptor, ErbB-2 -- antagonists & inhibitors KW - Breast Neoplasms -- metabolism KW - Amino Acid Sequence KW - Mice KW - Fluorenes -- chemistry KW - Tumor Cells, Cultured KW - Amino Acids -- chemistry KW - Molecular Sequence Data KW - Molecular Mimicry KW - Inhibitory Concentration 50 KW - Peptides, Cyclic -- chemistry KW - Peptides, Cyclic -- pharmacology KW - Phenylalanine -- analogs & derivatives KW - Proteins -- antagonists & inhibitors KW - Phenylalanine -- chemical synthesis KW - Phenylalanine -- pharmacology KW - src Homology Domains -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73564383?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Organic+letters&rft.atitle=Concise+and+enantioselective+synthesis+of+Fmoc-Pmp%28But%292-OH+and+design+of+potent+Pmp-containing+Grb2-SH2+domain+antagonists.&rft.au=Li%2C+Peng%3BZhang%2C+Manchao%3BPeach%2C+Megan+L%3BLiu%2C+Hongpeng%3BYang%2C+Dajun%3BRoller%2C+Peter+P&rft.aulast=Li&rft.aufirst=Peng&rft.date=2003-08-21&rft.volume=5&rft.issue=17&rft.spage=3095&rft.isbn=&rft.btitle=&rft.title=Organic+letters&rft.issn=15237060&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-03 N1 - Date created - 2003-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breastfeeding practices in a cohort of inner-city women: the role of contraindications. AN - 71572354; 12930560 AB - Little is known about the role of breastfeeding contraindications in breastfeeding practices. Our objectives were to 1) identify predictors of breastfeeding initiation and duration among a cohort of predominantly low-income, inner-city women, and 2) evaluate the contribution of breastfeeding contraindications to breastfeeding practices. Mother-infant dyads were systematically selected from 3 District of Columbia hospitals between 1995 and 1996. Breastfeeding contraindications and potential predictors of breastfeeding practices were identified through medical record reviews and interviews conducted after delivery (baseline). Interviews were conducted at 3-7 months postpartum and again at 7-12 months postpartum to determine breastfeeding initiation rates and duration. Multivariable logistic regression analysis was used to identify baseline factors associated with initiation of breastfeeding. Cox proportional hazards models were generated to identify baseline factors associated with duration of breastfeeding. Of 393 study participants, 201 (51%) initiated breastfeeding. A total of 61 women (16%) had at lease one documented contraindication to breastfeeding; 94% of these had a history of HIV infection and/or cocaine use. Of the 332 women with no documented contraindications, 58% initiated breastfeeding, vs. 13% of women with a contraindication. In adjusted analysis, factors most strongly associated with breastfeeding initiation were presence of a contraindication (adjusted odds ratio [AOR], 0.19; 95% confidence interval [CI], 0.08-0.47), and mother foreign-born (AOR, 4.90; 95% CI, 2.38-10.10). Twenty-five percent of study participants who did not initiate breastfeeding cited concern about passing dangerous things to their infants through breast milk. Factors associated with discontinuation of breastfeeding (all protective) included mother foreign-born (hazard ratio [HR], 0.55; 95% CI 0.39-0.77) increasing maternal age (HR for 5-year increments, 0.80; 95% CI, 0.69-0.92), and infant birth weight > or = 2500 grams (HR, 0.45; 95% CI, 0.26-0.80). Breastfeeding initiation rates and duration were suboptimal in this inner-city population. Many women who did not breastfeed had contraindications and/or were concerned about passing dangerous things to their infants through breast milk. It is important to consider the prevalence of contraindications to breastfeeding when evaluating breastfeeding practices in high-risk communities. JF - BMC public health AU - England, Lucinda AU - Brenner, Ruth AU - Bhaskar, Brinda AU - Simons-Morton, Bruce AU - Das, Abhik AU - Revenis, Mary AU - Mehta, Nitin AU - Clemens, John AD - Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, Department of Health and Human Services, Bethesda, MD 20895, USA. lbe9@cdc.gov Y1 - 2003/08/20/ PY - 2003 DA - 2003 Aug 20 SP - 28 VL - 3 KW - Index Medicus KW - Birth Weight KW - Humans KW - Infant, Newborn KW - Weaning KW - Infant KW - Poverty -- ethnology KW - Maternal Age KW - Adult KW - Cohort Studies KW - District of Columbia -- epidemiology KW - HIV Infections -- epidemiology KW - Female KW - Substance-Related Disorders -- epidemiology KW - Proportional Hazards Models KW - Breast Feeding -- statistics & numerical data KW - Breast Feeding -- adverse effects KW - Urban Population -- statistics & numerical data KW - Urban Population -- classification KW - Mothers -- statistics & numerical data KW - Breast Feeding -- ethnology KW - Attitude to Health -- ethnology KW - Maternal Behavior -- psychology KW - Mothers -- psychology KW - Maternal Behavior -- ethnology KW - Mothers -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71572354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+public+health&rft.atitle=Breastfeeding+practices+in+a+cohort+of+inner-city+women%3A+the+role+of+contraindications.&rft.au=England%2C+Lucinda%3BBrenner%2C+Ruth%3BBhaskar%2C+Brinda%3BSimons-Morton%2C+Bruce%3BDas%2C+Abhik%3BRevenis%2C+Mary%3BMehta%2C+Nitin%3BClemens%2C+John&rft.aulast=England&rft.aufirst=Lucinda&rft.date=2003-08-20&rft.volume=3&rft.issue=&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=BMC+public+health&rft.issn=1471-2458&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-24 N1 - Date created - 2004-05-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Pediatr Clin North Am. 2001 Feb;48(1):235-51 [11236729] Breastfeed Rev. 1999 Mar;7(1):5-16 [10197366] Pediatrics. 2001 Mar;107(3):543-8 [11230597] Ethn Dis. 2001 Winter;11(1):72-9 [11289255] Pediatrics. 2001 Aug;108(2):291-6 [11483790] Arch Dis Child. 2001 Sep;85(3):183-8 [11517096] Pediatrics. 2001 Sep;108(3):661-70 [11533333] Pediatrics. 2001 Sep;108(3):776-89 [11533352] J Pediatr. 2003 May;142(5):486-91 [12756378] Pediatrics. 1982 Aug;70(2):239-45 [7099789] Early Hum Dev. 1982 Dec 6;7(3):273-80 [7160337] Pediatrics. 1984 Oct;74(4 Pt 2):615-38 [6384916] Lancet. 1988 Aug 13;2(8607):365-8 [2899774] Pediatrics. 1988 Sep;82(3 Pt 2):496-503 [3405686] Diabetes. 1988 Dec;37(12):1625-32 [3192037] CMAJ. 1989 May 15;140(10):1159-64 [2713801] Pediatrics. 1989 Oct;84(4):626-32 [2780124] Am J Clin Nutr. 1989 Oct;50(4):868-74 [2801593] BMJ. 1990 Jan 6;300(6716):11-6 [2105113] Am J Dis Child. 1991 Mar;145(3):306-9 [2003480] Am J Med Sci. 1993 Jul;306(1):28-34 [8328506] Ann Epidemiol. 1993 Jul;3(4):387-92 [8275215] J Pediatr. 1995 Feb;126(2):191-7 [7844664] J Clin Epidemiol. 1994 Jul;47(7):739-46 [7722587] J Pediatr. 1995 May;126(5 Pt 1):696-702 [7751991] Acta Paediatr. 1997 Feb;86(2):173-7 [9055888] J Hum Lact. 1997 Mar;13(1):45-50 [9233185] Pediatrics. 1997 Dec;100(6):1035-9 [9411381] Vital Health Stat 1. 1997 Oct;(36):1-89 [9429337] Pediatrics. 1997 Apr;99(4):E12 [9099787] Pediatrics. 1998 Jun;101(6):E11 [9606253] Birth. 2000 Jun;27(2):91-6 [11251485] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional mutants of the sequence-specific transcription factor p53 and implications for master genes of diversity. AN - 73580271; 12909720 AB - There are many sources of genetic diversity, ranging from programmed mutagenesis in antibody genes to random mutagenesis during species evolution or development of cancer. We propose that mutations in DNA sequence-specific transcription factors that target response elements (REs) in many genes can also provide for rapid and broad phenotypic diversity, if the mutations lead to altered binding affinities at individual REs. To test this concept, we examined the in vivo transactivation capacity of wild-type human and murine p53 and 25 partial function mutants. The p53s were expressed in yeast from a rheostatable promoter, and the transactivation capacities toward >15 promoter REs upstream of a reporter gene were measured. Surprisingly, there was wide variation in transactivation by the mutant p53s toward the various REs. This is the first study to address directly the impact of mutations in a sequence-specific transcription factor on transactivation from a wide array of REs. We propose a master gene hypothesis for phenotypic diversity where the master gene is a single transcriptional activator (or repressor) that regulates many genes through different REs. Mutations of the master gene can lead to a variety of simultaneous changes in both the selection of targets and the extent of transcriptional modulation at the individual targets, resulting in a vast number of potential phenotypes that can be created with minimal mutational changes without altering existing protein-protein interactions. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Resnick, Michael A AU - Inga, Alberto AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. resnick@niehs.nih.gov Y1 - 2003/08/19/ PY - 2003 DA - 2003 Aug 19 SP - 9934 EP - 9939 VL - 100 IS - 17 SN - 0027-8424, 0027-8424 KW - Transcription Factors KW - 0 KW - Tumor Suppressor Protein p53 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - Humans KW - Mice KW - Tumor Suppressor Protein p53 -- metabolism KW - Transcription Factors -- genetics KW - Transcriptional Activation KW - Evolution, Molecular KW - Phenotype KW - Saccharomyces cerevisiae -- genetics KW - Promoter Regions, Genetic KW - DNA -- genetics KW - Genes, Reporter KW - Tumor Suppressor Protein p53 -- genetics KW - Amino Acid Substitution KW - Genetic Variation KW - Genes, p53 KW - Models, Genetic KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73580271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+mutants+of+the+sequence-specific+transcription+factor+p53+and+implications+for+master+genes+of+diversity.&rft.au=Resnick%2C+Michael+A%3BInga%2C+Alberto&rft.aulast=Resnick&rft.aufirst=Michael&rft.date=2003-08-19&rft.volume=100&rft.issue=17&rft.spage=9934&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 - 2003-10-29 N1 - Date created - 2003-08-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Oncogene. 2001 Jan 25;20(4):501-13 [11313981] Nat Rev Cancer. 2002 Oct;2(10):740-9 [12360277] Oncogene. 2001 Jun 7;20(26):3409-19 [11423991] Oncogene. 2001 Jun 14;20(27):3573-9 [11429705] Nat Biotechnol. 2001 Aug;19(8):773-6 [11479573] Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9330-5 [11481490] Mol Biol Evol. 2001 Sep;18(9):1764-70 [11504856] Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10208-13 [11517318] Curr Opin Microbiol. 2001 Oct;4(5):582-5 [11587936] Hum Mutat. 2002 Feb;19(2):149-64 [11793474] Trends Genet. 2002 Feb;18(2):90-5 [11818141] Science. 2002 Feb 1;295(5556):821-5 [11823633] Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2072-7 [11854503] Nat Rev Cancer. 2001 Dec;1(3):233-40 [11902578] Nat Genet. 2002 Mar;30(3):311-4 [11836502] Nat Genet. 2002 Mar;30(3):315-20 [11919562] Mol Cell Biol. 2002 May;22(10):3247-54 [11971958] Science. 2002 Apr 26;296(5568):750-2 [11976460] Hum Mutat. 2002 Jun;19(6):607-14 [12007217] Science. 2002 May 31;296(5573):1646-7 [12040180] Dev Dyn. 2002 Nov;225(3):351-7 [12412020] Mol Cell Biol. 2002 Dec;22(24):8612-25 [12446780] Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15632-7 [12438652] Gut. 2003 Feb;52(2):304-6 [12524418] Hum Mutat. 2003 Feb;21(2):138-45 [12552561] Nat Genet. 2003 Feb;33(2):138-44 [12548287] Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1931-6 [12574499] Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8424-9 [12826609] J Mol Biol. 1987 Jan 5;193(1):27-40 [3108514] Science. 1994 Jul 15;265(5170):346-55 [8023157] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3963-7 [7732013] Yeast. 1995 Apr 15;11(4):355-60 [7785336] Mol Cell Biol. 1996 Sep;16(9):4952-60 [8756654] Cell. 1997 Feb 7;88(3):323-31 [9039259] Microbiol Mol Biol Rev. 1998 Sep;62(3):586-96 [9729601] Am J Hum Genet. 1998 Nov;63(5):1316-28 [9792859] Semin Cancer Biol. 1998;8(5):345-57 [10101800] Oncogene. 1999 Apr 15;18(15):2451-9 [10229196] J Pathol. 1999 Jan;187(1):112-26 [10341712] Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8467-72 [12077306] Oncogene. 2002 Aug 22;21(37):5704-15 [12173040] Nature. 2002 Sep 5;419(6902):29-31 [12214221] Cell. 1999 Oct 15;99(2):143-53 [10535733] Cell. 2000 Jan 7;100(1):57-70 [10647931] Gene. 2000 Mar 21;245(2):319-28 [10717483] Cancer Res. 2000 Mar 15;60(6):1571-9 [10749125] Genes Dev. 2000 Apr 15;14(8):981-93 [10783169] Nature. 2000 Nov 16;408(6810):307-10 [11099028] Gene. 2000 Dec 30;261(1):19-25 [11164033] Nature. 2001 Feb 15;409(6822):832-3 [11237001] J Biol Chem. 2001 Apr 13;276(15):12120-7 [11152481] Mol Cell Biol. 2001 May;21(10):3375-86 [11313463] Oncogene. 2001 Jan 18;20(3):320-8 [11313961] Cancer Res. 2001 May 15;61(10):4092-7 [11358831] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of Rel sub(Mtb)-mediated adaptation to stationary phase in long-term persistence of Mycobacterium tuberculosis in mice AN - 18822473; 5695306 AB - Long-term survival of nonreplicating Mycobacterium tuberculosis (Mtb) is ensured by the coordinated shutdown of active metabolism through a broad transcriptional program called the stringent response. In Mtb, this response is initiated by the enzymatic action of Rel sub(Mtb) and deletion of rel sub(Mtb) produces a strain (H37Rv[Delta]rel sub(Mtb)) severely compromised in the maintenance of long-term viability. Although aerosol inoculation of mice with H37Rv[Delta]rel sub(Mtb) results in normal initial bacterial growth and containment, the ability of this strain to sustain chronic infection is severely impaired. Significant histopathologic differences were noted in lungs and spleens of mice infected with H37Rv[Delta]rel sub(Mtb) compared with controls throughout the course of the infection. Microarray analysis revealed that H37Rv[Delta]rel sub(Mtb) suffers from a generalized alteration of the transcriptional apparatus, as well as specific changes in the expression of virulence factors, cell-wall biosynthetic enzymes, heat shock proteins, and secreted antigens that may alter immune recognition of the recombinant organism. Thus, Rel sub(Mtb) is critical for the successful establishment of persistent infection in mice by altering the expression of antigenic and enzymatic factors that may contribute to successful latent infection. JF - Proceedings of the National Academy of Sciences, USA AU - Dahl, J L AU - Kraus, C N AU - Boshoff, HIM AU - Doan, B AU - Foley, K AU - Avarbock, D AU - Kaplan, G AU - Mizrahi, V AU - Rubin, H AU - Barry, CE III AD - Tuberculosis Research Section, National Institute of Allergy and Infectious Disease, Rockville, MD 20852, clifton_barry@nih.gov Y1 - 2003/08/19/ PY - 2003 DA - 2003 Aug 19 SP - 10026 EP - 10031 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 17 SN - 0027-8424, 0027-8424 KW - Rel protein KW - viability KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - J 02832:Antigenic properties and virulence KW - G 07320:Bacterial genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18822473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=The+role+of+Rel+sub%28Mtb%29-mediated+adaptation+to+stationary+phase+in+long-term+persistence+of+Mycobacterium+tuberculosis+in+mice&rft.au=Dahl%2C+J+L%3BKraus%2C+C+N%3BBoshoff%2C+HIM%3BDoan%2C+B%3BFoley%2C+K%3BAvarbock%2C+D%3BKaplan%2C+G%3BMizrahi%2C+V%3BRubin%2C+H%3BBarry%2C+CE+III&rft.aulast=Dahl&rft.aufirst=J&rft.date=2003-08-19&rft.volume=100&rft.issue=17&rft.spage=10026&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.1631248100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.1631248100 ER - TY - JOUR T1 - A randomized, double-blinded, placebo-controlled trial of intermittent administration of interleukin-2 and prednisone in subjects infected with human immunodeficiency virus. AN - 73588915; 12898439 AB - Intermittent administration of interleukin (IL)-2 produces significant and sustained increases in CD4(+) T lymphocyte count in human immunodeficiency virus (HIV)-infected subjects but can be associated with dose-limiting toxicities. The primary objective of this study was to determine whether concomitant administration of prednisone could decrease these toxicities. HIV-seropositive adults receiving highly active antiretroviral therapy (HAART) were randomized to receive either (1) intermittent subcutaneous IL-2 and placebo, (2) intermittent subcutaneous IL-2 and prednisone, (3) intermittent prednisone, or (4) intermittent placebo. Prednisone decreased levels of proinflammatory cytokines during IL-2 cycles but, despite induction of expression of CD25, blunted increases in IL-2-associated CD4(+) T lymphocyte count. Whereas intermittent administration of IL-2 reduced basal proliferation of CD4(+) T cells, this effect was inhibited by prednisone, suggesting that prednisone potentially interferes with IL-2's long-term effects on survival of T lymphocytes. JF - The Journal of infectious diseases AU - Tavel, Jorge A AU - Sereti, Irini AU - Walker, Robert E AU - Hahn, Barbara AU - Kovacs, Joseph A AU - Jagannatha, Shyla AU - Davey, Richard T AU - Falloon, Judith AU - Polis, Michael A AU - Masur, Henry AU - Metcalf, Julia A AU - Stevens, Randy AU - Rupert, Adam AU - Baseler, Michael AU - Lane, H Clifford AD - Office of the Clinical Director, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, US. jtavel@nih.gov. Y1 - 2003/08/15/ PY - 2003 DA - 2003 Aug 15 SP - 531 EP - 536 VL - 188 IS - 4 SN - 0022-1899, 0022-1899 KW - Anti-HIV Agents KW - 0 KW - Cytokines KW - Glucocorticoids KW - Interleukin-2 KW - Receptors, Interleukin-2 KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Double-Blind Method KW - Humans KW - Anti-HIV Agents -- administration & dosage KW - Cytokines -- metabolism KW - CD4 Lymphocyte Count KW - CD4-Positive T-Lymphocytes -- drug effects KW - Drug Therapy, Combination KW - Receptors, Interleukin-2 -- metabolism KW - Anti-HIV Agents -- therapeutic use KW - Glucocorticoids -- administration & dosage KW - Antiretroviral Therapy, Highly Active KW - Glucocorticoids -- therapeutic use KW - HIV KW - Cell Division KW - Interleukin-2 -- pharmacology KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - HIV Infections -- virology KW - Prednisone -- therapeutic use KW - Interleukin-2 -- therapeutic use KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Prednisone -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73588915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=A+randomized%2C+double-blinded%2C+placebo-controlled+trial+of+intermittent+administration+of+interleukin-2+and+prednisone+in+subjects+infected+with+human+immunodeficiency+virus.&rft.au=Tavel%2C+Jorge+A%3BSereti%2C+Irini%3BWalker%2C+Robert+E%3BHahn%2C+Barbara%3BKovacs%2C+Joseph+A%3BJagannatha%2C+Shyla%3BDavey%2C+Richard+T%3BFalloon%2C+Judith%3BPolis%2C+Michael+A%3BMasur%2C+Henry%3BMetcalf%2C+Julia+A%3BStevens%2C+Randy%3BRupert%2C+Adam%3BBaseler%2C+Michael%3BLane%2C+H+Clifford&rft.aulast=Tavel&rft.aufirst=Jorge&rft.date=2003-08-15&rft.volume=188&rft.issue=4&rft.spage=531&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-09 N1 - Date created - 2003-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human campylobacteriosis: a challenge for the veterinary profession. AN - 73577612; 12930081 JF - Journal of the American Veterinary Medical Association AU - Altekruse, Sean F AU - Tollefson, Linda K AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd MSC 7234, Rockville, MD 20852, USA. Y1 - 2003/08/15/ PY - 2003 DA - 2003 Aug 15 SP - 445 EP - 452 VL - 223 IS - 4 SN - 0003-1488, 0003-1488 KW - Index Medicus KW - Travel KW - Animals KW - Risk Factors KW - Humans KW - Food Contamination KW - Immunocompromised Host KW - Campylobacter Infections -- complications KW - Zoonoses KW - Campylobacter Infections -- prevention & control KW - Campylobacter Infections -- transmission UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73577612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Veterinary+Medical+Association&rft.atitle=Human+campylobacteriosis%3A+a+challenge+for+the+veterinary+profession.&rft.au=Altekruse%2C+Sean+F%3BTollefson%2C+Linda+K&rft.aulast=Altekruse&rft.aufirst=Sean&rft.date=2003-08-15&rft.volume=223&rft.issue=4&rft.spage=445&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Veterinary+Medical+Association&rft.issn=00031488&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-24 N1 - Date created - 2003-08-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Am Vet Med Assoc. 2003 Oct 15;223(8):1109-10; author reply 1111 [14584733] J Am Vet Med Assoc. 2003 Nov 1;223(9):1252-3; author reply 1253-4 [14621206] J Am Vet Med Assoc. 2003 Oct 15;223(8):1110-1; author reply 1111 [14584734] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. AN - 73576328; 12915604 AB - This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens. Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned. A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P =.048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P =.033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P =.04). Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Yang, James C AU - Sherry, Richard M AU - Steinberg, Seth M AU - Topalian, Suzanne L AU - Schwartzentruber, Douglas J AU - Hwu, Patrick AU - Seipp, Claudia A AU - Rogers-Freezer, Linda AU - Morton, Kathleen E AU - White, Donald E AU - Liewehr, David J AU - Merino, Maria J AU - Rosenberg, Steven A AD - Surgery Branch, Biostatistics and Data Management Section, Department of Pathology, National Cancer Institute/NIH, Room 2B-37, Building 10, 9000 Rockville Pike, Bethesda, MD 20892, USA. james_yang@nih.gov Y1 - 2003/08/15/ PY - 2003 DA - 2003 Aug 15 SP - 3127 EP - 3132 VL - 21 IS - 16 SN - 0732-183X, 0732-183X KW - Interleukin-2 KW - 0 KW - Index Medicus KW - Humans KW - Prognosis KW - Middle Aged KW - Male KW - Female KW - Survival Analysis KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- drug therapy KW - Interleukin-2 -- administration & dosage KW - Carcinoma, Renal Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73576328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Randomized+study+of+high-dose+and+low-dose+interleukin-2+in+patients+with+metastatic+renal+cancer.&rft.au=Yang%2C+James+C%3BSherry%2C+Richard+M%3BSteinberg%2C+Seth+M%3BTopalian%2C+Suzanne+L%3BSchwartzentruber%2C+Douglas+J%3BHwu%2C+Patrick%3BSeipp%2C+Claudia+A%3BRogers-Freezer%2C+Linda%3BMorton%2C+Kathleen+E%3BWhite%2C+Donald+E%3BLiewehr%2C+David+J%3BMerino%2C+Maria+J%3BRosenberg%2C+Steven+A&rft.aulast=Yang&rft.aufirst=James&rft.date=2003-08-15&rft.volume=21&rft.issue=16&rft.spage=3127&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 - 2003-09-15 N1 - Date created - 2003-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1985 Dec 5;313(23):1485-92 [3903508] J Clin Oncol. 2001 Aug 1;19(15):3477-82 [11481353] J Urol. 1996 Jan;155(1):19-25 [7490829] JAMA. 1986 Dec 12;256(22):3117-24 [3491225] Mol Biother. 1990 Mar;2(1):18-26 [2334534] J Clin Oncol. 1990 Oct;8(10):1650-6 [2213101] J Clin Oncol. 1992 Jul;10(7):1119-23 [1607917] J Clin Oncol. 1993 Sep;11(9):1809-16 [8355047] Br J Cancer. 1994 Jun;69(6):1111-4 [8198979] J Clin Oncol. 1994 Aug;12(8):1572-6 [8040669] Cancer. 1994 Dec 15;74(12):3212-22 [7982185] J Clin Oncol. 1995 Feb;13(2):497-501 [7844611] Arch Ital Urol Androl. 1997 Feb;69(1):41-7 [9181905] Cancer. 1998 Aug 15;83(4):797-805 [9708948] Ann Surg. 1998 Sep;228(3):307-19 [9742914] Cancer J Sci Am. 1996 Mar-Apr;2(2):91-8 [9166506] Cancer J Sci Am. 1997 Dec;3 Suppl 1:S79-84 [9457400] Cancer J Sci Am. 1997 Dec;3 Suppl 1:S73-8 [9457399] J Pathol. 1997 Oct;183(2):131-3 [9390023] Cancer J Sci Am. 1997 Dec;3 Suppl 1:S70-2 [9457398] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. AN - 73565260; 12837810 AB - Platinum-containing chemotherapy regimens are the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), although toxicity is common and may significantly affect the patient's quality of life (QoL). This trial aimed to assess whether a combination of gemcitabine and vinorelbine had benefits in terms of QoL, without influencing negatively on survival, compared with cisplatin-containing regimens. Patients with stage IIIB (effusion and supraclavicular nodes) or IV documented NSCLC who were younger than 70 years of age were randomly assigned gemcitabine plus vinorelbine (GemVin) or either gemcitabine plus cisplatin or vinorelbine plus cisplatin (cisplatin-based). European Organization for Research and Treatment of Cancer scales were used for QoL analysis. Five hundred one patients were randomly assigned to treatment. The median age was 62 years. There were no significant differences in global QoL scores between the two arms after 2 months of treatment. However, worsening scores for appetite, vomiting, and alopecia were significantly more common in the cisplatin-based arm. Median survival was 38 v 32 weeks and median progression-free survival was 23 v 17 weeks in the cisplatin-based versus GemVin arms, respectively. For the GemVin arm the hazard ratio for death was 1.15 (90% confidence interval [CI], 0.96 to 1.37) and the hazard ratio for progression was 1.29 (90% CI, 1.10 to 1.52). Grade 3 or 4 myelosuppression, vomiting, alopecia, and ototoxicity were significantly more frequent with cisplatin-based treatment. Global QoL is not improved with GemVin, although advantages in some components of QoL were apparent. GemVin is less toxic than standard cisplatin-based chemotherapy. There is a nonsignificant slight survival advantage with cisplatin-based chemotherapy. GemVin could be offered to advanced NSCLC patients who express concern about toxicity. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Gridelli, Cesare AU - Gallo, Ciro AU - Shepherd, Frances A AU - Illiano, Alfonso AU - Piantedosi, Francovito AU - Robbiati, Sergio Federico AU - Manzione, Luigi AU - Barbera, Santi AU - Frontini, Luciano AU - Veltri, Enzo AU - Findlay, Brian AU - Cigolari, Silvio AU - Myers, Robert AU - Ianniello, Giovanni P AU - Gebbia, Vittorio AU - Gasparini, Giampietro AU - Fava, Sergio AU - Hirsh, Vera AU - Bezjak, Andrea AU - Seymour, Lesley AU - Perrone, Francesco AD - Clinical Trials Unit, National Cancer Institute, Via M Semmola, 80131 Naples, Italy. cgridelli@libero.it Y1 - 2003/08/15/ PY - 2003 DA - 2003 Aug 15 SP - 3025 EP - 3034 VL - 21 IS - 16 SN - 0732-183X, 0732-183X KW - Deoxycytidine KW - 0W860991D6 KW - Vinblastine KW - 5V9KLZ54CY KW - gemcitabine KW - B76N6SBZ8R KW - Cisplatin KW - Q20Q21Q62J KW - vinorelbine KW - Q6C979R91Y KW - Index Medicus KW - Canada KW - Humans KW - Adult KW - Quality of Life KW - Aged KW - Middle Aged KW - Male KW - Italy KW - Female KW - Survival Analysis KW - Vinblastine -- analogs & derivatives KW - Carcinoma, Non-Small-Cell Lung -- mortality KW - Deoxycytidine -- analogs & derivatives KW - Lung Neoplasms -- drug therapy KW - Vinblastine -- administration & dosage KW - Deoxycytidine -- administration & dosage KW - Lung Neoplasms -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Cisplatin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73565260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gemcitabine+plus+vinorelbine+compared+with+cisplatin+plus+vinorelbine+or+cisplatin+plus+gemcitabine+for+advanced+non-small-cell+lung+cancer%3A+a+phase+III+trial+of+the+Italian+GEMVIN+Investigators+and+the+National+Cancer+Institute+of+Canada+Clinical+Trials+Group.&rft.au=Gridelli%2C+Cesare%3BGallo%2C+Ciro%3BShepherd%2C+Frances+A%3BIlliano%2C+Alfonso%3BPiantedosi%2C+Francovito%3BRobbiati%2C+Sergio+Federico%3BManzione%2C+Luigi%3BBarbera%2C+Santi%3BFrontini%2C+Luciano%3BVeltri%2C+Enzo%3BFindlay%2C+Brian%3BCigolari%2C+Silvio%3BMyers%2C+Robert%3BIanniello%2C+Giovanni+P%3BGebbia%2C+Vittorio%3BGasparini%2C+Giampietro%3BFava%2C+Sergio%3BHirsh%2C+Vera%3BBezjak%2C+Andrea%3BSeymour%2C+Lesley%3BPerrone%2C+Francesco&rft.aulast=Gridelli&rft.aufirst=Cesare&rft.date=2003-08-15&rft.volume=21&rft.issue=16&rft.spage=3025&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 - 2003-09-15 N1 - Date created - 2003-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 2003 Aug 15;21(16):3009-10 [12837812] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene expression dose-response changes in microarrays after exposure of human peripheral lung epithelial cells to nickel(II). AN - 73556768; 12915101 AB - Occupational exposure to nickel compounds is associated with lung cancer risk; both genotoxic and epigenetic mechanisms have been proposed. For comprehensive examination of the acute effects of nickel(II) acetate on gene expression in cultured human peripheral lung epithelial HPL1D cells, microarray analyses were carried out with cDNA chips (approximately 8000 cDNAs). Cells were exposed for 24 h to nontoxic (50, 100, and 200 microM) or toxic (400, 800, and 1600 microM) nickel(II) concentrations. Cluster analysis was applied to the 868 genes with > or = 2-fold change at any concentration. Two main clusters showed marked up- or down-regulation at the highest, toxic concentrations. The data further subdivided into 10 highly cohesive clusters with high probability, and of these only 2 had the same response trend at low nontoxic as at high concentrations, an observation of clear relevance to the process of high- to low-dose extrapolation in risk assessment. There were 113 genes showing > or = 2-fold change at the three lower nontoxic concentrations, those most relevant to in vivo carcinogenesis. In addition to expected responses of metallothionein, ferritin, and heat-shock proteins, the results revealed for the first time changed expression of some potential cancer-related genes in response to low-dose Ni(II): RhoA, dyskerin, interferon regulatory factor 1, RAD21 homologue, and tumor protein, translationally controlled. Overall, most of the genes impacted by nontoxic concentrations of nickel(II) acetate related to gene transcription, protein synthesis and stability, cytoskeleton, signaling, metabolism, cell membrane, and extracellular matrix. JF - Toxicology and applied pharmacology AU - Cheng, Robert Y S AU - Zhao, Ailian AU - Alvord, W Gregory AU - Powell, Douglas A AU - Bare, Robert M AU - Masuda, Akira AU - Takahashi, Takashi AU - Anderson, Lucy M AU - Kasprzak, Kazimierz S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Bldg. 538, Ft. Detrick, Frederick, MD 21702, USA. rcheng@ncifcrf.gov Y1 - 2003/08/15/ PY - 2003 DA - 2003 Aug 15 SP - 22 EP - 39 VL - 191 IS - 1 SN - 0041-008X, 0041-008X KW - Membrane Proteins KW - 0 KW - Nuclear Proteins KW - Proteins KW - Ribosomal Proteins KW - Nickel KW - 7OV03QG267 KW - Index Medicus KW - Protein Biosynthesis KW - Nuclear Proteins -- genetics KW - Extracellular Matrix -- metabolism KW - Ribosomal Proteins -- genetics KW - Dose-Response Relationship, Drug KW - Neural Networks (Computer) KW - Humans KW - Algorithms KW - Membrane Proteins -- genetics KW - Reverse Transcriptase Polymerase Chain Reaction KW - Proteins -- genetics KW - Extracellular Matrix -- drug effects KW - Ribosomal Proteins -- drug effects KW - Membrane Proteins -- biosynthesis KW - Nuclear Proteins -- biosynthesis KW - Protein Binding -- genetics KW - Gene Expression Regulation -- drug effects KW - Down-Regulation -- drug effects KW - Cluster Analysis KW - Epithelial Cells -- metabolism KW - Lung Diseases -- chemically induced KW - Oligonucleotide Array Sequence Analysis KW - Epithelial Cells -- pathology KW - Lung Diseases -- pathology KW - Lung Diseases -- metabolism KW - Nickel -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73556768?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Gene+expression+dose-response+changes+in+microarrays+after+exposure+of+human+peripheral+lung+epithelial+cells+to+nickel%28II%29.&rft.au=Cheng%2C+Robert+Y+S%3BZhao%2C+Ailian%3BAlvord%2C+W+Gregory%3BPowell%2C+Douglas+A%3BBare%2C+Robert+M%3BMasuda%2C+Akira%3BTakahashi%2C+Takashi%3BAnderson%2C+Lucy+M%3BKasprzak%2C+Kazimierz+S&rft.aulast=Cheng&rft.aufirst=Robert+Y&rft.date=2003-08-15&rft.volume=191&rft.issue=1&rft.spage=22&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-05 N1 - Date created - 2003-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alanine-scanning mutations in domain 4 of anthrax toxin protective antigen reveal residues important for binding to the cellular receptor and to a neutralizing monoclonal antibody. AN - 73535999; 12771151 AB - A panel of variants with alanine substitutions in the small loop of anthrax toxin protective antigen domain 4 was created to determine individual amino acid residues critical for interactions with the cellular receptor and with a neutralizing monoclonal antibody, 14B7. Substituted protective antigen proteins were analyzed by cellular cytotoxicity assays, and their interactions with antibody were measured by plasmon surface resonance and analytical ultracentrifugation. Residue Asp683 was the most critical for cell binding and toxicity, causing an approximately 1000-fold reduction in toxicity, but was not a large factor for interactions with 14B7. Substitutions in residues Tyr681, Asn682, and Pro686 also reduced toxicity significantly, by 10-100-fold. Of these, only Asn682 and Pro686 were also critical for interactions with 14B7. However, residues Lys684, Leu685, Leu687, and Tyr688 were critical for 14B7 binding without greatly affecting toxicity. The K684A and L685A variants exhibited wild type levels of toxicity in cell culture assays; the L687A and Y688A variants were reduced only 1.5- and 5-fold, respectively. JF - The Journal of biological chemistry AU - Rosovitz, M J AU - Schuck, Peter AU - Varughese, Mini AU - Chopra, Arun P AU - Mehra, Varsha AU - Singh, Yogendra AU - McGinnis, Lisa M AU - Leppla, Stephen H AD - Microbial Pathogenesis Section, NIAID, National Institutes of Health, Bethesda, Maryland 20892-4350, USA. Y1 - 2003/08/15/ PY - 2003 DA - 2003 Aug 15 SP - 30936 EP - 30944 VL - 278 IS - 33 SN - 0021-9258, 0021-9258 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, Bacterial KW - Bacterial Toxins KW - Receptors, Peptide KW - anthrax toxin KW - anthrax toxin receptors KW - Aspartic Acid KW - 30KYC7MIAI KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Aspartic Acid -- metabolism KW - Binding Sites -- immunology KW - Animals KW - Aspartic Acid -- genetics KW - Alanine -- genetics KW - Models, Chemical KW - Mice KW - Protein Structure, Tertiary KW - Mutation KW - Cell Line KW - Macrophages -- cytology KW - Bacterial Toxins -- genetics KW - Receptors, Peptide -- metabolism KW - Macrophages -- microbiology KW - Macrophages -- immunology KW - Bacterial Toxins -- chemistry KW - Bacterial Toxins -- immunology KW - Antibodies, Monoclonal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73535999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alanine-scanning+mutations+in+domain+4+of+anthrax+toxin+protective+antigen+reveal+residues+important+for+binding+to+the+cellular+receptor+and+to+a+neutralizing+monoclonal+antibody.&rft.au=Rosovitz%2C+M+J%3BSchuck%2C+Peter%3BVarughese%2C+Mini%3BChopra%2C+Arun+P%3BMehra%2C+Varsha%3BSingh%2C+Yogendra%3BMcGinnis%2C+Lisa+M%3BLeppla%2C+Stephen+H&rft.aulast=Rosovitz&rft.aufirst=M&rft.date=2003-08-15&rft.volume=278&rft.issue=33&rft.spage=30936&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 - 2003-11-10 N1 - Date created - 2003-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential modulation of hippocampal chemical-induced injury response by ebselen, pentoxifylline, and TNFalpha-, IL-1alpha-, and IL-6-neutralizing antibodies. AN - 73528317; 12898537 AB - The proinflammatory cytokines tumor necrosis factor (TNFalpha), interleukin-1 (IL-1alpha), and interleukin-6 (IL-6) have been associated with various models of hippocampal damage. To examine their role in initiation of an acute hippocampal injury response, 21-day-old male CD-1 mice received an acute intraperitoneal (i.p.) injection of trimethyltin hydroxide (TMT; 2.0 mg/kg) to produce necrosis of dentate granule neurons, astrocyte, and microglia reactivity. Tremors and intermittent seizures were evident at 24 hr. Intercellular adhesion molecule-1 (ICAM-1), glial fibrillary acidic protein (GFAP), anti-apoptotic TNFalpha-inducible early response gene (A-20), macrophage inflammatory protein (MIP)-1alpha, TNFalpha, IL-1alpha, IL-6, and caspase 3 mRNA levels were significantly elevated. Pretreatment with the antioxidant, ebselen, decreased ICAM-1, A-20, and TNFbeta elevations. Pentoxifylline blocked elevations in A-20 and decreased elevations in GFAP mRNA levels. Neither prevented histopathology or behavioral effects. Intracisternal injection of TNFalpha-neutralizing antibody significantly inhibited both behavioral effects and histopathology. RNase protection assays showed that TMT-induced elevations in mRNA levels for ICAM-1, A-20, GFAP, MIP-1alpha, IL-1alpha, TNFalpha, TNFbeta, and caspase 3 were blocked by anti-TNFalpha. These data demonstrate a significant role for TNFalpha in an acute neuro-injury in the absence of contribution from infiltrating cells. The cerebellum shows limited if any damage after TMT; however, in combination with the i.c.v. injection, elevations were seen in GFAP and in EB-22, a murine acute-phase response gene homologous to the alpha (1)-antichymotrypsin gene. Elevations were similar for artificial cerebral spinal fluid and anti-IL-1alpha, and significantly increased with anti-TNFalpha, anti-IL-6, or the combination of antibodies. Responses seen in the cerebellum suggest synergistic interactions between the baseline state of the cell and manipulations in the cytokine environment. Data suggests a role for TNFalpha in the pathogenesis of hippocampal injury induced by TMT. Published 2003 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Jean Harry, G AU - Bruccoleri, Alessandra AU - Lefebvre d'Hellencourt, Christian AD - Neurotoxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Harry@niehs.nih.gov Y1 - 2003/08/15/ PY - 2003 DA - 2003 Aug 15 SP - 526 EP - 536 VL - 73 IS - 4 SN - 0360-4012, 0360-4012 KW - Antibodies KW - 0 KW - Azoles KW - Cytokines KW - Drug Combinations KW - Glial Fibrillary Acidic Protein KW - Interleukin-1 KW - Interleukin-6 KW - Lectins KW - Neuroprotective Agents KW - Neurotoxins KW - Organoselenium Compounds KW - RNA, Messenger KW - Trimethyltin Compounds KW - Tumor Necrosis Factor-alpha KW - ebselen KW - 40X2P7DPGH KW - trimethyltin hydroxide KW - 56-24-6 KW - Pentoxifylline KW - SD6QCT3TSU KW - Index Medicus KW - Animals KW - Interleukin-1 -- immunology KW - Tumor Necrosis Factor-alpha -- immunology KW - Glial Fibrillary Acidic Protein -- metabolism KW - Disease Models, Animal KW - RNA, Messenger -- biosynthesis KW - Cerebellum -- metabolism KW - Azoles -- therapeutic use KW - Pentoxifylline -- therapeutic use KW - Interleukin-6 -- immunology KW - Gene Expression Regulation -- drug effects KW - Nuclease Protection Assays -- methods KW - Lectins -- metabolism KW - Male KW - Microglia -- metabolism KW - Interleukin-6 -- metabolism KW - Mice KW - Neurotoxins -- toxicity KW - Trimethyltin Compounds -- toxicity KW - Mice, Inbred Strains KW - Interleukin-1 -- metabolism KW - Organoselenium Compounds -- therapeutic use KW - Cerebellum -- drug effects KW - Tumor Necrosis Factor-alpha -- metabolism KW - Microglia -- drug effects KW - Antibodies -- immunology KW - Cytokines -- genetics KW - Hippocampus -- metabolism KW - Cytokines -- immunology KW - Brain Injuries -- immunology KW - Cytokines -- metabolism KW - Brain Injuries -- prevention & control KW - Hippocampus -- pathology KW - Neuroprotective Agents -- therapeutic use KW - Brain Injuries -- chemically induced KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73528317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Differential+modulation+of+hippocampal+chemical-induced+injury+response+by+ebselen%2C+pentoxifylline%2C+and+TNFalpha-%2C+IL-1alpha-%2C+and+IL-6-neutralizing+antibodies.&rft.au=Jean+Harry%2C+G%3BBruccoleri%2C+Alessandra%3BLefebvre+d%27Hellencourt%2C+Christian&rft.aulast=Jean+Harry&rft.aufirst=G&rft.date=2003-08-15&rft.volume=73&rft.issue=4&rft.spage=526&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 - 2003-09-08 N1 - Date created - 2003-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modelling and analysing exchangeable binary data with random cluster sizes. AN - 73491758; 12872298 AB - Correlated binary data occur very frequently in cluster sample surveys, dependent repeated cancer screening, teratological experiments, ophthalmologic and otolaryngologic studies, and other clinical trials. The standard methods to analyse these data include the use of beta-binomial models and generalized estimating equations with third and fourth moments specified by 'working matrices'. However, in many applications it is reasonable to assume that the data from the same cluster are exchangeable. When all sampled clusters have equal sizes, Bowman and George introduced maximum likelihood estimates (MLEs) of the population parameters such as the marginal means, moments, and correlations of order two and higher. They also extended their approach to sampled clusters with unequal sizes. It seems that their extension has a gap. This paper points out the source of this gap and shows that estimates introduced by Bowman and George are not the MLEs of the parameters which are used to identify the joint distribution of correlated binary data. We show that the MLEs of the population parameters have no closed form in general and should be calculated by numerical methods. We apply our results and a generalized estimating equation procedure to a data set from a double-blind randomized clinical trial comparing two antibiotics, cefaclor and amoxicillin, used for the treatment of acute otitis media. To see the performance of the MLEs with small or moderate sample sizes, several simulation studies are also conducted. Published in 2003 by John Wiley & Sons, Ltd. JF - Statistics in medicine AU - Xu, Jian-Lun AU - Prorok, Philip C AD - Biometry Research Group, National Cancer Institute, Executive Plaza North, Suite 3131, 6130 Executive Blvd, MSC 7354, Bethesda, MD 20892-7354, USA. jianxu@helix.nih.gov Y1 - 2003/08/15/ PY - 2003 DA - 2003 Aug 15 SP - 2401 EP - 2416 VL - 22 IS - 15 SN - 0277-6715, 0277-6715 KW - Anti-Bacterial Agents KW - 0 KW - Cefaclor KW - 69K7K19H4L KW - Amoxicillin KW - 804826J2HU KW - Index Medicus KW - United States KW - Anti-Bacterial Agents -- therapeutic use KW - Amoxicillin -- therapeutic use KW - Randomized Controlled Trials as Topic KW - Cefaclor -- therapeutic use KW - Humans KW - Otitis Media -- drug therapy KW - Likelihood Functions KW - Models, Statistical KW - Cluster Analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73491758?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+medicine&rft.atitle=Modelling+and+analysing+exchangeable+binary+data+with+random+cluster+sizes.&rft.au=Xu%2C+Jian-Lun%3BProrok%2C+Philip+C&rft.aulast=Xu&rft.aufirst=Jian-Lun&rft.date=2003-08-15&rft.volume=22&rft.issue=15&rft.spage=2401&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 completed - 2003-12-04 N1 - Date created - 2003-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Area under the curve as a dose metric for promotional responses following 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure AN - 18871125; 5726703 AB - An underlying basis of risk assessment is that an equivalent risk for a specified dose metric exists that allows for extrapolation of dose-response relationships between species. To better understand the use of area under the curve (AUC) as a dose metric for complex biological responses following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure, a study was designed using a physiologically based pharmacokinetic model in the female Sprague-Dawley rat that would result in equivalent AUCs of total liver TCDD with differing patterns of exposure. In the first group, rats received a high peak dose of 3500 ng TCDD/kg twice per week in the first week followed by a lower TCDD dose of 81 ng/kg twice per week for the remainder of the study. In the second group, rats received a gavage dose of 350 ng TCDD/kg in corn oil twice per week for the study duration of 15 weeks. Age-matched control rats received corn oil as a vehicle control. Placental glutathione S-transferase (PGST)-positive foci were measured in representative liver lobes by immunohistochemistry, as a representative complex biological response resulting from TCDD exposure. The median volume fraction was 0.045% in control rats and was significantly elevated in TCDD treatment groups. However, the volume fraction of PGST-positive foci was significantly higher in the TCDD group given the high peak dose during the first week of TCDD treatment compared with the group receiving the same average daily dose over the study duration: 0.74 versus 0.20%, respectively. These findings suggest that the peak magnitude of TCDD in liver rather than AUC may play a significant role in the induction of complex biological responses by TCDD. JF - Toxicology and Applied Pharmacology AU - Kim, AH AU - Kohn, M C AU - Nyska, A AU - Walker, N J AD - Curriculum in Toxicology, University of North Carolina at Chapel Hill, 509 Mary Ellen Jones Building, CB#7270, Chapel Hill, NC 27599, USA, walker3@niehs.nih.gov Y1 - 2003/08/15/ PY - 2003 DA - 2003 Aug 15 SP - 12 EP - 21 PB - Elsevier Science (USA) VL - 191 IS - 1 SN - 0041-008X, 0041-008X KW - Toxicology Abstracts KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18871125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Area+under+the+curve+as+a+dose+metric+for+promotional+responses+following+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+exposure&rft.au=Kim%2C+AH%3BKohn%2C+M+C%3BNyska%2C+A%3BWalker%2C+N+J&rft.aulast=Kim&rft.aufirst=AH&rft.date=2003-08-15&rft.volume=191&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1016%2FS0041-008X%2803%2900225-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0041-008X(03)00225-4 ER - TY - JOUR T1 - Comparative analyses of multi-species sequences from targeted genomic regions. AN - 73570939; 12917688 AB - The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates. JF - Nature AU - Thomas, J W AU - Touchman, J W AU - Blakesley, R W AU - Bouffard, G G AU - Beckstrom-Sternberg, S M AU - Margulies, E H AU - Blanchette, M AU - Siepel, A C AU - Thomas, P J AU - McDowell, J C AU - Maskeri, B AU - Hansen, N F AU - Schwartz, M S AU - Weber, R J AU - Kent, W J AU - Karolchik, D AU - Bruen, T C AU - Bevan, R AU - Cutler, D J AU - Schwartz, S AU - Elnitski, L AU - Idol, J R AU - Prasad, A B AU - Lee-Lin, S-Q AU - Maduro, V V B AU - Summers, T J AU - Portnoy, M E AU - Dietrich, N L AU - Akhter, N AU - Ayele, K AU - Benjamin, B AU - Cariaga, K AU - Brinkley, C P AU - Brooks, S Y AU - Granite, S AU - Guan, X AU - Gupta, J AU - Haghighi, P AU - Ho, S-L AU - Huang, M C AU - Karlins, E AU - Laric, P L AU - Legaspi, R AU - Lim, M J AU - Maduro, Q L AU - Masiello, C A AU - Mastrian, S D AU - McCloskey, J C AU - Pearson, R AU - Stantripop, S AU - Tiongson, E E AU - Tran, J T AU - Tsurgeon, C AU - Vogt, J L AU - Walker, M A AU - Wetherby, K D AU - Wiggins, L S AU - Young, A C AU - Zhang, L-H AU - Osoegawa, K AU - Zhu, B AU - Zhao, B AU - Shu, C L AU - De Jong, P J AU - Lawrence, C E AU - Smit, A F AU - Chakravarti, A AU - Haussler, D AU - Green, P AU - Miller, W AU - Green, E D AD - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892,USA. Y1 - 2003/08/14/ PY - 2003 DA - 2003 Aug 14 SP - 788 EP - 793 VL - 424 IS - 6950 KW - CFTR protein, human KW - 0 KW - DNA Transposable Elements KW - Cystic Fibrosis Transmembrane Conductance Regulator KW - 126880-72-6 KW - Index Medicus KW - Phylogeny KW - Animals KW - Sequence Alignment KW - Sequence Homology, Nucleic Acid KW - Humans KW - Chromosomes, Human, Pair 7 -- genetics KW - Mutagenesis -- genetics KW - DNA Transposable Elements -- genetics KW - Mammals -- genetics KW - Species Specificity KW - Genome KW - Cystic Fibrosis Transmembrane Conductance Regulator -- genetics KW - Conserved Sequence -- genetics KW - Vertebrates -- genetics KW - Evolution, Molecular KW - Genomics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73570939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Comparative+analyses+of+multi-species+sequences+from+targeted+genomic+regions.&rft.au=Thomas%2C+J+W%3BTouchman%2C+J+W%3BBlakesley%2C+R+W%3BBouffard%2C+G+G%3BBeckstrom-Sternberg%2C+S+M%3BMargulies%2C+E+H%3BBlanchette%2C+M%3BSiepel%2C+A+C%3BThomas%2C+P+J%3BMcDowell%2C+J+C%3BMaskeri%2C+B%3BHansen%2C+N+F%3BSchwartz%2C+M+S%3BWeber%2C+R+J%3BKent%2C+W+J%3BKarolchik%2C+D%3BBruen%2C+T+C%3BBevan%2C+R%3BCutler%2C+D+J%3BSchwartz%2C+S%3BElnitski%2C+L%3BIdol%2C+J+R%3BPrasad%2C+A+B%3BLee-Lin%2C+S-Q%3BMaduro%2C+V+V+B%3BSummers%2C+T+J%3BPortnoy%2C+M+E%3BDietrich%2C+N+L%3BAkhter%2C+N%3BAyele%2C+K%3BBenjamin%2C+B%3BCariaga%2C+K%3BBrinkley%2C+C+P%3BBrooks%2C+S+Y%3BGranite%2C+S%3BGuan%2C+X%3BGupta%2C+J%3BHaghighi%2C+P%3BHo%2C+S-L%3BHuang%2C+M+C%3BKarlins%2C+E%3BLaric%2C+P+L%3BLegaspi%2C+R%3BLim%2C+M+J%3BMaduro%2C+Q+L%3BMasiello%2C+C+A%3BMastrian%2C+S+D%3BMcCloskey%2C+J+C%3BPearson%2C+R%3BStantripop%2C+S%3BTiongson%2C+E+E%3BTran%2C+J+T%3BTsurgeon%2C+C%3BVogt%2C+J+L%3BWalker%2C+M+A%3BWetherby%2C+K+D%3BWiggins%2C+L+S%3BYoung%2C+A+C%3BZhang%2C+L-H%3BOsoegawa%2C+K%3BZhu%2C+B%3BZhao%2C+B%3BShu%2C+C+L%3BDe+Jong%2C+P+J%3BLawrence%2C+C+E%3BSmit%2C+A+F%3BChakravarti%2C+A%3BHaussler%2C+D%3BGreen%2C+P%3BMiller%2C+W%3BGreen%2C+E+D&rft.aulast=Thomas&rft.aufirst=J&rft.date=2003-08-14&rft.volume=424&rft.issue=6950&rft.spage=788&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=1476-4687&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-21 N1 - Date created - 2003-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenosine A(2A) receptor antagonist treatment of Parkinson's disease. AN - 73565497; 12913186 AB - Observations in animal models suggest that A(2A) antagonists confer benefit by modulating dopaminergic effects on the striatal dysfunction associated with motor disability. This double-blind, placebo-controlled, proof-of-principle study evaluated the pathogenic contribution and therapeutic potential of adenosine A(2A) receptor-mediated mechanisms in Parkinson disease (PD) and levodopa-induced motor complications. Fifteen patients with moderate to advanced PD consented to participate. All were randomized to either the selective A(2A) antagonist KW-6002 or matching placebo capsules in a 6-week dose-rising design (40 and 80 mg/day). Motor function was rated on the Unified PD Rating Scale. KW-6002 alone or in combination with a steady-state IV infusion of each patient's optimal levodopa dose had no effect on parkinsonian severity. At a low dose of levodopa, however, KW-6002 (80 mg) potentiated the antiparkinsonian response by 36% (p < 0.02), but with 45% less dyskinesia compared with that induced by optimal dose levodopa alone (p < 0.05). All cardinal parkinsonian signs improved, especially resting tremor. In addition, KW-6002 prolonged the efficacy half-time of levodopa by an average of 47 minutes (76%; p < 0.05). No medically important drug toxicity occurred. The results support the hypothesis that A(2A) receptor mechanisms contribute to symptom production in PD and that drugs able to selectively block these receptors may help palliate symptoms in levodopa-treated patients with this disorder. JF - Neurology AU - Bara-Jimenez, W AU - Sherzai, A AU - Dimitrova, T AU - Favit, A AU - Bibbiani, F AU - Gillespie, M AU - Morris, M J AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/08/12/ PY - 2003 DA - 2003 Aug 12 SP - 293 EP - 296 VL - 61 IS - 3 KW - Adenosine A2 Receptor Antagonists KW - 0 KW - Antiparkinson Agents KW - Purines KW - istradefylline KW - 2GZ0LIK7T4 KW - Levodopa KW - 46627O600J KW - Carbidopa KW - MNX7R8C5VO KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Carbidopa -- administration & dosage KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Safety KW - Levodopa -- administration & dosage KW - Treatment Outcome KW - Levodopa -- therapeutic use KW - Motor Activity -- drug effects KW - Middle Aged KW - Drug Synergism KW - Levodopa -- adverse effects KW - Female KW - Male KW - Antiparkinson Agents -- adverse effects KW - Antiparkinson Agents -- administration & dosage KW - Purines -- administration & dosage KW - Purines -- adverse effects KW - Antiparkinson Agents -- therapeutic use KW - Purines -- therapeutic use KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73565497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Adenosine+A%282A%29+receptor+antagonist+treatment+of+Parkinson%27s+disease.&rft.au=Bara-Jimenez%2C+W%3BSherzai%2C+A%3BDimitrova%2C+T%3BFavit%2C+A%3BBibbiani%2C+F%3BGillespie%2C+M%3BMorris%2C+M+J%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Bara-Jimenez&rft.aufirst=W&rft.date=2003-08-12&rft.volume=61&rft.issue=3&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=1526-632X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-25 N1 - Date created - 2003-08-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Neurology. 2003 Aug 12;61(3):286-7 [12913183] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protective efficacy of neuroactive steroids against cocaine kindled-seizures in mice. AN - 73643310; 12921865 AB - Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse. JF - European journal of pharmacology AU - Kaminski, Rafal M AU - Gasior, Maciej AU - Carter, Richard B AU - Witkin, Jeffrey M AD - NIDA Addiction Research Center, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. kaminskr@ninds.nih.gov Y1 - 2003/08/08/ PY - 2003 DA - 2003 Aug 08 SP - 217 EP - 222 VL - 474 IS - 2-3 SN - 0014-2999, 0014-2999 KW - Neuroprotective Agents KW - 0 KW - ganaxolone KW - 98WI44OHIQ KW - Pregnanolone KW - BXO86P3XXW KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Mice KW - Neuroprotective Agents -- therapeutic use KW - Male KW - Neuroprotective Agents -- pharmacology KW - Seizures -- chemically induced KW - Kindling, Neurologic -- drug effects KW - Pregnanolone -- therapeutic use KW - Cocaine -- toxicity KW - Pregnanolone -- pharmacology KW - Seizures -- prevention & control KW - Kindling, Neurologic -- physiology KW - Pregnanolone -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73643310?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+pharmacology&rft.atitle=Protective+efficacy+of+neuroactive+steroids+against+cocaine+kindled-seizures+in+mice.&rft.au=Kaminski%2C+Rafal+M%3BGasior%2C+Maciej%3BCarter%2C+Richard+B%3BWitkin%2C+Jeffrey+M&rft.aulast=Kaminski&rft.aufirst=Rafal&rft.date=2003-08-08&rft.volume=474&rft.issue=2-3&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=European+journal+of+pharmacology&rft.issn=00142999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-23 N1 - Date created - 2003-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Random mutagenesis of the M3 muscarinic acetylcholine receptor expressed in yeast. Identification of point mutations that "silence" a constitutively active mutant M3 receptor and greatly impair receptor/G protein coupling. AN - 73524439; 12750375 AB - The M3 muscarinic receptor is a prototypical member of the class I family of G protein-coupled receptors (GPCRs). To facilitate studies on the structural mechanisms governing M3 receptor activation, we generated an M3 receptor-expressing yeast strain (Saccharomyces cerevisiae) that requires agonist-dependent M3 receptor activation for cell growth. By using receptor random mutagenesis followed by a genetic screen in yeast, we initially identified a point mutation at the cytoplasmic end of transmembrane domain (TM) VI (Q490L) that led to robust agonist-independent M3 receptor signaling in both yeast and mammalian cells. To explore further the molecular mechanisms by which point mutations can render GPCRs constitutively active, we subjected a region of the Q490L mutant M3 receptor that included TM V-VII to random mutagenesis. We then applied a yeast genetic screen to identify second-site mutations that could suppress the activating effects of the Q490L mutation and restore wild-type receptor-like function to the Q490L mutant receptor. This analysis led to the identification of 12 point mutations that allowed the Q490L mutant receptor to function in a fashion similar to the wild-type receptor. These amino acid substitutions mapped to two distinct regions of the M3 receptor, the exofacial segments of TM V and VI and the cytoplasmic ends of TM V-VII. Strikingly, in the absence of the activating Q490L mutation, all recovered point mutations severely reduced the efficiency of receptor/G protein coupling, indicating that the targeted residues play important roles in receptor activation and/or receptor/G protein coupling. This strategy should be generally applicable to identify sites in GPCRs that are critically involved in receptor function. JF - The Journal of biological chemistry AU - Schmidt, Clarice AU - Li, Bo AU - Bloodworth, Lanh AU - Erlenbach, Isolde AU - Zeng, Fu-Yue AU - Wess, Jürgen AD - Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/08/08/ PY - 2003 DA - 2003 Aug 08 SP - 30248 EP - 30260 VL - 278 IS - 32 SN - 0021-9258, 0021-9258 KW - Ligands KW - 0 KW - Receptor, Muscarinic M3 KW - Receptors, Muscarinic KW - Carbachol KW - 8Y164V895Y KW - Rhodopsin KW - 9009-81-8 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - COS Cells KW - Mutagenesis KW - Mutagenesis, Site-Directed KW - Rats KW - Promoter Regions, Genetic KW - Saccharomyces cerevisiae -- metabolism KW - Cytoplasm -- metabolism KW - Molecular Sequence Data KW - Point Mutation KW - Rhodopsin -- chemistry KW - Signal Transduction KW - Cell Division KW - Plasmids -- metabolism KW - Dose-Response Relationship, Drug KW - Models, Molecular KW - Amino Acid Sequence KW - Polymerase Chain Reaction KW - Cattle KW - Blotting, Western KW - Kinetics KW - Cell Membrane -- metabolism KW - Protein Structure, Tertiary KW - Carbachol -- pharmacology KW - Mutation KW - Receptors, Muscarinic -- genetics KW - GTP-Binding Proteins -- chemistry KW - Receptors, Muscarinic -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73524439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Random+mutagenesis+of+the+M3+muscarinic+acetylcholine+receptor+expressed+in+yeast.+Identification+of+point+mutations+that+%22silence%22+a+constitutively+active+mutant+M3+receptor+and+greatly+impair+receptor%2FG+protein+coupling.&rft.au=Schmidt%2C+Clarice%3BLi%2C+Bo%3BBloodworth%2C+Lanh%3BErlenbach%2C+Isolde%3BZeng%2C+Fu-Yue%3BWess%2C+J%C3%BCrgen&rft.aulast=Schmidt&rft.aufirst=Clarice&rft.date=2003-08-08&rft.volume=278&rft.issue=32&rft.spage=30248&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 - 2003-09-24 N1 - Date created - 2003-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Using genetics to understand auditory function and improve diagnosis. AN - 85379994; pmid-12923417 JF - Ear and hearing AU - Battey, James F AD - National Institute on Deafness and Other Communication Disorders, Bethesda, MD USA. batteyj@nided.nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 266 EP - 269 VL - 24 IS - 4 SN - 0196-0202, 0196-0202 KW - Index Medicus KW - National Library of Medicine KW - Agnosia: diagnosis KW - Agnosia: genetics KW - Animals KW - Disease Models, Animal KW - *Hearing Disorders: diagnosis KW - *Hearing Disorders: genetics KW - Hearing Loss: diagnosis KW - Hearing Loss: genetics KW - Humans KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85379994?accountid=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=Ear+and+hearing&rft.atitle=Using+genetics+to+understand+auditory+function+and+improve+diagnosis.&rft.au=Battey%2C+James+F&rft.aulast=Battey&rft.aufirst=James&rft.date=2003-08-01&rft.volume=24&rft.issue=4&rft.spage=266&rft.isbn=&rft.btitle=&rft.title=Ear+and+hearing&rft.issn=01960202&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Recent advances in the understanding of syndromic forms of hearing loss. AN - 85378621; pmid-12923420 JF - Ear and hearing AU - Friedman, Thomas B AU - Schultz, Julie M AU - Ben-Yosef, Tamar AU - Pryor, Shannon P AU - Lagziel, Ayala AU - Fisher, Rachel A AU - Wilcox, Edward R AU - Riazuddin, Saima AU - Ahmed, Zubair M AU - Belyantseva, Inna A AU - Griffith, Andrew J AD - Section on Human Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Rockville, MD, USA. Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 289 EP - 302 VL - 24 IS - 4 SN - 0196-0202, 0196-0202 KW - Index Medicus KW - National Library of Medicine KW - Chromosome Disorders: genetics KW - Chromosomes, Human, X KW - Genes, Dominant KW - *Hearing Loss, Sensorineural: genetics KW - Humans KW - Syndrome KW - Waardenburg's Syndrome: genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85378621?accountid=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=Ear+and+hearing&rft.atitle=Recent+advances+in+the+understanding+of+syndromic+forms+of+hearing+loss.&rft.au=Friedman%2C+Thomas+B%3BSchultz%2C+Julie+M%3BBen-Yosef%2C+Tamar%3BPryor%2C+Shannon+P%3BLagziel%2C+Ayala%3BFisher%2C+Rachel+A%3BWilcox%2C+Edward+R%3BRiazuddin%2C+Saima%3BAhmed%2C+Zubair+M%3BBelyantseva%2C+Inna+A%3BGriffith%2C+Andrew+J&rft.aulast=Friedman&rft.aufirst=Thomas&rft.date=2003-08-01&rft.volume=24&rft.issue=4&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Ear+and+hearing&rft.issn=01960202&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Lower risk of Parkinson's disease in an admixed population of European and Indian origins. AN - 85377702; pmid-12889081 AB - We studied whether the occurrence of Parkinson's disease (PD) in the Anglo-Indians, an admixed population of European and Asian Indian origin, differs from Indians living in the same environment. Epidemiological studies show considerably higher prevalence of PD amongst white compared to non-white populations. Normal Indians contain a approximately 40% lower number of melanized nigral neurons compared to Caucasians from the UK. Anglo-Indians are an admixed population of European and Indian origin. We used the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria (steps 1 and 2) to diagnose PD in 84 of 493 residents (Indians, 409; Anglo-Indians, 84) living in elderly homes in Bangalore, India. Of these 84, 80 were Indians (19.5%) and 4 were Anglo-Indians (4.8%). Occurrence of PD is nearly five times higher amongst Indians compared to the Anglo-Indians (odds ratio, 3.9; 95% confidence interval, 1.3-12.9). We conclude that an admixture population of European and Indian origins, rather than averaging, might result in reduced occurrences of PD. Hence, studying an admixed population could provide crucial insights into understanding genetic mechanisms in the etiopathogenesis of PD.Copyright 2003 Movement Disorder Society JF - Movement disorders : official journal of the Movement Disorder Society AU - Ragothaman, Mona AU - Murgod, Uday A AU - Gururaj, Gopalkrishna AU - Kumaraswamy, Subbakrishna D AU - Muthane, Uday AD - Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 912 EP - 914 VL - 18 IS - 8 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Aged KW - Aged, 80 and over KW - Europe: ethnology KW - Female KW - Great Britain: epidemiology KW - Humans KW - India: ethnology KW - Male KW - Middle Aged KW - *Parkinson Disease: ethnology KW - Phenotype KW - Population Dynamics KW - Prevalence KW - Risk Factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85377702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Lower+risk+of+Parkinson%27s+disease+in+an+admixed+population+of+European+and+Indian+origins.&rft.au=Ragothaman%2C+Mona%3BMurgod%2C+Uday+A%3BGururaj%2C+Gopalkrishna%3BKumaraswamy%2C+Subbakrishna+D%3BMuthane%2C+Uday&rft.aulast=Ragothaman&rft.aufirst=Mona&rft.date=2003-08-01&rft.volume=18&rft.issue=8&rft.spage=912&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Comparison of cognitive performances during a placebo period and an atypical antipsychotic treatment period in schizophrenia: critical examination of confounds. AN - 85292241; pmid-12799617 AB - Although previous studies report cognitive improvement following atypical antipsychotic administration in schizophrenia (SC), few placebo-controlled within-subject studies with examination of confounds (symptom reduction, cooperation, learning, and outliers) have been reported. The present study examines the effects of atypicals and confounds upon cognition in SC. The hypothesis tested was that relative to placebo, atypicals as a general class of medication would elicit cognitive improvement in SC. In all, 19 patients with SC (15 males) completed the double-blind, counterbalanced, randomized within-subject study of the effects of atypical antipsychotics (risperidone, clozapine, olanzapine, or quetiapine) vs placebo administration upon cognitive performance in the domains of executive function, attention, memory, language, visual perception, and general intellect. Significant cognitive improvement during atypical antipsychotic administration relative to placebo withdrawal occurred in most cognitive domains with robust improvements in intelligence (p=0.001), memory (p=0.0009), and fluency (p <0.002) even after outliers and unmotivated performances were excluded. These findings suggest that relative to placebo withdrawal, atypicals improve cognitive performance in SC. However, this finding may not be specific to atypicals, since analogous studies of typicals have not been performed. JF - Neuropsychopharmacology AU - Weickert, Thomas W AU - Goldberg, Terry E AU - Marenco Stefano AU - Bigelow, Llewellyn B AU - Egan, Michael F AU - Weinberger, Daniel R AD - Clinical Brain Disorders Branch, National Institute of Mental Health/NIH, Building 10 Room 4N202, MSC 1379, Bethesda, MD 20892, USA. PY - 2003 SP - 1491 EP - 1500 VL - 28 IS - 8 SN - 0893-133X, 0893-133X KW - Schizophrenia KW - Analysis of Variance KW - Comparative Study KW - Double-Blind Method KW - Human KW - Adult KW - Psychotic Disorders KW - Neuropsychological Tests KW - Antipsychotic Agents KW - Male KW - Female KW - Cognition KW - Schizophrenic Psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85292241?accountid=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=Neuropsychopharmacology&rft.atitle=Comparison+of+cognitive+performances+during+a+placebo+period+and+an+atypical+antipsychotic+treatment+period+in+schizophrenia%3A+critical+examination+of+confounds.&rft.au=Weickert%2C+Thomas+W%3BGoldberg%2C+Terry+E%3BMarenco+Stefano%3BBigelow%2C+Llewellyn+B%3BEgan%2C+Michael+F%3BWeinberger%2C+Daniel+R&rft.aulast=Weickert&rft.aufirst=Thomas&rft.date=2003-08-01&rft.volume=28&rft.issue=8&rft.spage=1491&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Administration of oxaliplatin to patients with renal dysfunction: a preliminary report of the national cancer institute organ dysfunction working group. AN - 75745422; 14523791 AB - Oxaliplatin is an approved agent with clinical activity in the treatment of advanced colorectal cancer. Preliminary pharmacokinetic evidence suggests that oxaliplatin is predominantly cleared by renal excretion; however, formal dosing guidelines in patients with renal impairment are lacking. The National Cancer Institute Organ Dysfunction Working Group initiated the following dose-escalation pharmacokinetic trial of oxaliplatin in patients with varying degrees of renal function. Thirty-seven patients with various solid tumor malignancies were stratified into four renal dysfunction groups based on their measured 24-hour urinary creatinine clearance (CrCL). Patients in group A (controls) all had a CrCL >or= 60 mL/min; group B patients had mild renal dysfunction with CrCLs ranging from 40 to 59 mL/min; group C patients had moderate renal dysfunction with CrCLs of 20 to 39 mL/min; and patients with a CrCL 20 mL/min. JF - Seminars in oncology AU - Takimoto, Chris H AU - Remick, Scot C AU - Sharma, Sunil AU - Mani, Sridhar AU - Ramanathan, Ramesh K AU - Doroshow, James H AU - Hamilton, Anne AU - Mulkerin, Daniel AU - Graham, Martin AU - Lockwood, Graham F AU - Ivy, Percy AU - Egorin, Merrill AU - Greenslade, Denis AU - Goetz, Andrew AU - Grem, Jean L AD - Medicine Branch at Navy, National Naval Medical Center, National Cancer Institute, Bethesda, MD, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 20 EP - 25 VL - 30 IS - 4 Suppl 15 SN - 0093-7754, 0093-7754 KW - Antineoplastic Agents KW - 0 KW - Organoplatinum Compounds KW - oxaliplatin KW - 04ZR38536J KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Neoplasms -- drug therapy KW - Neoplasms -- complications KW - Creatinine -- urine KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Male KW - Female KW - Organoplatinum Compounds -- pharmacokinetics KW - Organoplatinum Compounds -- adverse effects KW - Organoplatinum Compounds -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Kidney Diseases -- complications KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75745422?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Administration+of+oxaliplatin+to+patients+with+renal+dysfunction%3A+a+preliminary+report+of+the+national+cancer+institute+organ+dysfunction+working+group.&rft.au=Takimoto%2C+Chris+H%3BRemick%2C+Scot+C%3BSharma%2C+Sunil%3BMani%2C+Sridhar%3BRamanathan%2C+Ramesh+K%3BDoroshow%2C+James+H%3BHamilton%2C+Anne%3BMulkerin%2C+Daniel%3BGraham%2C+Martin%3BLockwood%2C+Graham+F%3BIvy%2C+Percy%3BEgorin%2C+Merrill%3BGreenslade%2C+Denis%3BGoetz%2C+Andrew%3BGrem%2C+Jean+L&rft.aulast=Takimoto&rft.aufirst=Chris&rft.date=2003-08-01&rft.volume=30&rft.issue=4+Suppl+15&rft.spage=20&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 - 2003-11-12 N1 - Date created - 2003-10-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spontaneous pituitary abnormalities and mammary hyperplasia in FVB/NCr mice: implications for mouse modeling. AN - 75735751; 14524419 AB - The FVB/N mouse strain is widely used in the generation of transgenic mouse models. We have observed that mammary glands of wild-type virgin female FVB/NCr mice frequently have the morphologic and histologic appearance of a gland during pregnancy. By 13 months of age, the mammary glands of more than 40% of the mice examined had lobuloalveolar hyperplasia that was characterized by the presence of secretory alveoli and distended ducts apparently containing secretory material. The prevalence of this phenotype further increased with age. The mammary phenotype was highly correlated with the presence of proliferative, prolactin-secreting lesions in the pituitary gland. In mice aged 18 to 23 months, hyperplasia of the pars distalis was seen in 11 of 21 mice (52%), and a further 4 of 21 mice (19%) had pituitary adenomas. Pituitary hyperplasia was already evident in some mice as young as nine months. The pituitary phenotype was also associated with high prevalence (4/6 mice) of spontaneous mammary tumors in aged multiparous, but not virgin FVB/NCr mice. This high prevalence of pituitary abnormalities and their effects on the mammary gland have important consequences for the interpretation of new phenotypes generated in transgenic models using this mouse substrain. JF - Comparative medicine AU - Wakefield, Lalage M AU - Thordarson, Gudmundur AU - Nieto, Ana I AU - Shyamala, G AU - Galvez, Jose J AU - Anver, Miriam R AU - Cardiff, Robert D AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 424 EP - 432 VL - 53 IS - 4 SN - 1532-0820, 1532-0820 KW - Index Medicus KW - Mammary Neoplasms, Animal -- etiology KW - Animals KW - Hyperplasia KW - Mammary Neoplasms, Animal -- pathology KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Female KW - Pituitary Gland -- pathology KW - Mice, Inbred Strains KW - Mammary Glands, Animal -- pathology KW - Pituitary Diseases -- veterinary KW - Pituitary Diseases -- complications KW - Pituitary Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75735751?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Comparative+medicine&rft.atitle=Spontaneous+pituitary+abnormalities+and+mammary+hyperplasia+in+FVB%2FNCr+mice%3A+implications+for+mouse+modeling.&rft.au=Wakefield%2C+Lalage+M%3BThordarson%2C+Gudmundur%3BNieto%2C+Ana+I%3BShyamala%2C+G%3BGalvez%2C+Jose+J%3BAnver%2C+Miriam+R%3BCardiff%2C+Robert+D&rft.aulast=Wakefield&rft.aufirst=Lalage&rft.date=2003-08-01&rft.volume=53&rft.issue=4&rft.spage=424&rft.isbn=&rft.btitle=&rft.title=Comparative+medicine&rft.issn=15320820&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-05-06 N1 - Date created - 2003-10-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phenomenological exploration of spirituality among African American women recovering from substance abuse. AN - 75710274; 14508773 AB - Spirituality among African American women recovering from substance abuse is a recovery phenomena: little is known about the individual's experience in this process. The ameliorating effect of spirituality covering a broad range of positive outcomes has been consistent across populations, regardless of gender, race, study design, and religious affiliation. Giorgi's phenomenological method was used to explore and described the meaning of spirituality of 15 African American women recovering from substance abuse. The findings are described and discussed relative to the state of the science on spirituality. Implications for substance abuse and recovery practitioners are presented. JF - Archives of psychiatric nursing AU - Wright, Violet L AD - NIH/NINDS, Stroke Neuroscience Unit, Bethesda, MD 20891-1294, USA. wrightv@ninds.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 173 EP - 185 VL - 17 IS - 4 SN - 0883-9417, 0883-9417 KW - Index Medicus KW - Nursing KW - Humans KW - Adult KW - Female KW - African Americans -- psychology KW - Spirituality KW - Convalescence KW - Substance-Related Disorders -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75710274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychiatric+nursing&rft.atitle=A+phenomenological+exploration+of+spirituality+among+African+American+women+recovering+from+substance+abuse.&rft.au=Wright%2C+Violet+L&rft.aulast=Wright&rft.aufirst=Violet&rft.date=2003-08-01&rft.volume=17&rft.issue=4&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Archives+of+psychiatric+nursing&rft.issn=08839417&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-01 N1 - Date created - 2003-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of environmental stressors on opiate and psychostimulant reinforcement, reinstatement and discrimination in rats: a review. AN - 75705166; 14505687 AB - Studies in humans suggest that exposure to life stressors is correlated with compulsive drug abuse and relapse to drugs during periods of abstinence. The behavioral and neurobiological mechanisms involved in the effect of stress on drug abuse, however, are not known. Here, we review data from studies using preclinical models in rats on the effect of environmental stressors on opiate and psychostimulant reinforcement, as measured by the intravenous drug self-administration and conditioned place preference procedures, on relapse to these drugs, as measured by the reinstatement procedure, and on the subjective effects of these drugs, as measured by the drug discrimination procedure. The results of the studies reviewed here suggest that while stressors are important modulators of the behavioral effects of opiate and psychostimulant drugs, the effect of stress on behavior in these animal models is stressor-specific, and to some degree, procedure- and drug-class-specific. The review of studies on the neurobiological mechanisms underlying stress-drug interactions in these animal models indicate that central noradrenaline and extrahypothalamic corticotropin-releasing factor mediate the effect of one form of stress (intermittent footshock) on reinstatement of opiate and psychostimulant seeking after prolonged drug-free periods. At present, however, little is known about the neuronal events that mediate the effect of environmental stressors on opiate and psychostimulant reinforcement or discrimination. The broader implications of the data reviewed here for future research and for the treatment of opiate and psychostimulant addiction are briefly discussed. JF - Neuroscience and biobehavioral reviews AU - Lu, Lin AU - Shepard, Jack D AU - Hall, F Scott AU - Shaham, Yavin AD - Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 457 EP - 491 VL - 27 IS - 5 SN - 0149-7634, 0149-7634 KW - Central Nervous System Stimulants KW - 0 KW - Narcotics KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Rats KW - Opioid-Related Disorders -- physiopathology KW - Animals KW - Restraint, Physical KW - Central Nervous System Stimulants -- pharmacology KW - Self Administration KW - Norepinephrine -- metabolism KW - Noise KW - Maternal Deprivation KW - Food Deprivation KW - Social Isolation KW - Electroshock KW - Narcotics -- pharmacology KW - Corticotropin-Releasing Hormone -- metabolism KW - Substance-Related Disorders -- physiopathology KW - Stress, Psychological -- metabolism KW - Stress, Psychological -- physiopathology KW - Discrimination (Psychology) KW - Reinforcement (Psychology) KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75705166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+biobehavioral+reviews&rft.atitle=Effect+of+environmental+stressors+on+opiate+and+psychostimulant+reinforcement%2C+reinstatement+and+discrimination+in+rats%3A+a+review.&rft.au=Lu%2C+Lin%3BShepard%2C+Jack+D%3BHall%2C+F+Scott%3BShaham%2C+Yavin&rft.aulast=Lu&rft.aufirst=Lin&rft.date=2003-08-01&rft.volume=27&rft.issue=5&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Neuroscience+and+biobehavioral+reviews&rft.issn=01497634&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-26 N1 - Date created - 2003-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity characterization of environmental chemicals by the US National Toxicology Program: an overview. AN - 73653759; 12971699 AB - The US National Toxicology Program (NTP) is an interagency program whose mission is to evaluate agents of public health concern by developing and applying the tools of modern toxicology and molecular biology. Chemicals substances or physical agents selected for toxicology and carcinogenesis evaluations by the NTP are usually studied in a series of subacute (14-day exposure), subchronic (90-day exposure) and chronic (2-year exposure) studies in rodents. The NTP has published more than 500 reports of the findings and conclusions from its toxicology and carcinogenesis studies. In more specialized studies, the NTP also evaluates adverse effects on the structure and function of the immune, reproductive, nervous, and respiratory systems. The program attempts to evaluate and appropriately incorporate new technologies to improve the way we study the toxicity of chemicals. For example, the program has extensively evaluated several transgenic mouse models for their potential use as short-term cancer screens and has been a full participant in an international effort to examine their usefulness in pharmaceutical registration. Toxicogenomics, an emerging scientific field that examines the expression of thousands of genes simultaneously in response to chemical exposure, holds promise for future application to better understand the underlying mechanisms of chemical toxicity. A number of public health issues being addressed by the NTP are not only of national importance but also have global impact, such as the potential for endocrine disruptors to influence development and carcinogenesis and the safety of herbal medicines and dietary supplements. The program participates in the preparation of national and international toxicity testing guidelines and the findings from NTP studies are widely used for risk assessments by international organizations and federal agencies. The NTP maintains databases that contain toxicity, and health and safety information on a large number of chemicals. These databases are available from the NTP web site (http://ntp-server.niehs.nih.gov) and are accessed over 100000 times a month from around the world. JF - International journal of hygiene and environmental health AU - Chhabra, Rajendra S AU - Bucher, John R AU - Wolfe, Mary AU - Portier, Christopher AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. chhabraR@niehs.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 437 EP - 445 VL - 206 IS - 4-5 SN - 1438-4639, 1438-4639 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - United States KW - Animals KW - Public Health KW - Humans KW - National Institutes of Health (U.S.) KW - Program Development KW - Carcinogenicity Tests KW - Toxicogenetics KW - Plants, Medicinal -- adverse effects KW - National Health Programs KW - Health Priorities KW - Environmental Pollutants -- toxicity KW - Toxicity Tests -- methods KW - Toxicology -- organization & administration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73653759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+hygiene+and+environmental+health&rft.atitle=Toxicity+characterization+of+environmental+chemicals+by+the+US+National+Toxicology+Program%3A+an+overview.&rft.au=Chhabra%2C+Rajendra+S%3BBucher%2C+John+R%3BWolfe%2C+Mary%3BPortier%2C+Christopher&rft.aulast=Chhabra&rft.aufirst=Rajendra&rft.date=2003-08-01&rft.volume=206&rft.issue=4-5&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=International+journal+of+hygiene+and+environmental+health&rft.issn=14384639&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-17 N1 - Date created - 2003-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonmalarial infant deaths and DDT use for malaria control. AN - 73647819; 12967494 AB - Although dichlorodiphenyl trichloroethane (DDT) is being banned worldwide, countries in sub-Saharan Africa have sought exemptions for malaria control. Few studies show illness in children from the use of DDT, and the possibility of risks to them from DDT use has been minimized. However, plausible if inconclusive studies associate DDT with more preterm births and shorter duration of lactation, which raise the possibility that DDT does indeed have such toxicity. Assuming that these associations are causal, we estimated the increase in infant deaths that might result from DDT spraying. The estimated increases are of the same order of magnitude as the decreases from effective malaria control. Unintended consequences of DDT use need to be part of the discussion of modern vector control policy. JF - Emerging infectious diseases AU - Chen, Aimin AU - Rogan, Walter J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 960 EP - 964 VL - 9 IS - 8 SN - 1080-6040, 1080-6040 KW - DDT KW - CIW5S16655 KW - Index Medicus KW - Malaria -- prevention & control KW - Humans KW - Infant, Newborn KW - Africa South of the Sahara KW - Female KW - Pregnancy KW - Milk, Human -- chemistry KW - DDT -- blood KW - Infant Mortality KW - DDT -- adverse effects KW - DDT -- therapeutic use KW - Obstetric Labor, Premature -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73647819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Emerging+infectious+diseases&rft.atitle=Nonmalarial+infant+deaths+and+DDT+use+for+malaria+control.&rft.au=Chen%2C+Aimin%3BRogan%2C+Walter+J&rft.aulast=Chen&rft.aufirst=Aimin&rft.date=2003-08-01&rft.volume=9&rft.issue=8&rft.spage=960&rft.isbn=&rft.btitle=&rft.title=Emerging+infectious+diseases&rft.issn=10806040&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-05 N1 - Date created - 2003-09-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Parasitol Today. 2000 Mar;16(3):119-21 [10689332] Trop Med Int Health. 1997 Sep;2(9):855-62 [9315044] J Cancer Res Clin Oncol. 2000 Apr;126(4):246 [10782899] Arch Dis Child Fetal Neonatal Ed. 2000 May;82(3):F200-4 [10794786] Soc Sci Med. 2000 Jul;51(2):185-97 [10832567] Lancet. 2000 Feb 5;355(9202):451-5 [10841125] JAMA. 2000 Aug 16;284(7):843-9 [10938173] Paediatr Perinat Epidemiol. 2000 Jul;14(3):219-26 [10949213] BMJ. 2000 Dec 2;321(7273):1403-5 [11099289] Am J Trop Med Hyg. 2001 Jan-Feb;64(1-2 Suppl):28-35 [11425175] Lancet. 2001 Jul 14;358(9276):110-4 [11463412] Environ Health Perspect. 2001 Dec;109(12):1291-9 [11748038] J Pediatr. 2002 Jan;140(1):33-9 [11815761] J Toxicol Environ Health A. 2002 Jan 25;65(2):165-82 [11820504] Nature. 2002 Feb 7;415(6872):670-2 [11832954] Environ Health Perspect. 2002 Feb;110(2):125-8 [11836138] Paediatr Drugs. 2002;4(3):191-203 [11909011] Lancet. 2002 Jul 27;360(9329):284-9 [12147371] Contraception. 1984 Dec;30(6):505-22 [6241559] Lancet. 1987 Aug 8;2(8554):319-22 [2886775] Am J Public Health. 1987 Oct;77(10):1294-7 [3115123] Pediatrics. 1989 Jan;83(1):31-40 [2909974] J Toxicol Environ Health. 1990 Oct;31(2):93-115 [2213927] Bull World Health Organ. 1990;68(6):761-8 [2073714] J Toxicol Environ Health. 1991 Jun;33(2):141-55 [2051491] J Trop Pediatr. 1994 Jun;40(3):137-43 [8078111] Am J Public Health. 1995 Apr;85(4):504-8 [7702113] Z Geburtshilfe Neonatol. 1995 Mar-Apr;199(2):65-70 [7788580] Trop Med Int Health. 1996 Apr;1(2):139-46 [8665377] Soc Sci Med. 1997 Feb;44(3):413-21 [9004375] Biochem Pharmacol. 1997 Apr 25;53(8):1161-72 [9175721] Early Hum Dev. 1997 Oct 29;49 Suppl:S143-55 [9363423] Emerg Infect Dis. 1999 Mar-Apr;5(2):309-11 [10221895] J Infect Dis. 1999 Jun;179(6):1580-3 [10228088] J Cancer Res Clin Oncol. 1999;125(3-4):219-25 [10235477] Bull World Health Organ. 1999;77(8):624-40 [10516785] Comment In: Emerg Infect Dis. 2004 Jun;10(6):1170-1; author reply 1171-2 [15224677] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental health moves into the 21st century. AN - 73642188; 12971681 AB - Over the past half century, environmental health research has branched from a descriptive, observational process into one of hypothesis driven and mechanistically based science. Nevertheless, the meaning of observed effects of exposures in experimental systems to human public health remains elusive. Recent advances in genetics and "omics" hold great promise to further our abilities to assess potential human health effects and to manage exposures properly. But the comfort of 100% certainty will not be available in the foreseeable future, leaving us with the challenge of designing relevant experiments and test systems upon which to base "logical" policy in risk management. JF - International journal of hygiene and environmental health AU - Schonwalder, Christopher AU - Olden, Kenneth AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-2233, USA. schonwalder@niehs.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 263 EP - 267 VL - 206 IS - 4-5 SN - 1438-4639, 1438-4639 KW - Index Medicus KW - United States KW - Animals KW - United States Environmental Protection Agency KW - Toxicology -- trends KW - Humans KW - Molecular Epidemiology -- trends KW - Toxicogenetics -- trends KW - Risk Assessment KW - Environmental Health -- trends KW - Forecasting UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73642188?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+hygiene+and+environmental+health&rft.atitle=Environmental+health+moves+into+the+21st+century.&rft.au=Schonwalder%2C+Christopher%3BOlden%2C+Kenneth&rft.aulast=Schonwalder&rft.aufirst=Christopher&rft.date=2003-08-01&rft.volume=206&rft.issue=4-5&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=International+journal+of+hygiene+and+environmental+health&rft.issn=14384639&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-17 N1 - Date created - 2003-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Introduction: National Institute on Alcohol Abuse and Alcoholism workshop on treatment research priorities and health disparities. AN - 73640754; 12966328 JF - Alcoholism, clinical and experimental research AU - Le Fauve, Charlene E AU - Lowman, Cherry AU - Litten, Raye Z AU - Mattson, Margaret E AD - National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Department of Health and Human Service, Bethesda, Maryland 20892-7003, USA. clefauve@mail.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 1318 EP - 1320 VL - 27 IS - 8 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - United States KW - Humans KW - National Institutes of Health (U.S.) KW - Practice Guidelines as Topic KW - Research Design -- trends KW - Alcoholism -- therapy KW - Research Design -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73640754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Introduction%3A+National+Institute+on+Alcohol+Abuse+and+Alcoholism+workshop+on+treatment+research+priorities+and+health+disparities.&rft.au=Le+Fauve%2C+Charlene+E%3BLowman%2C+Cherry%3BLitten%2C+Raye+Z%3BMattson%2C+Margaret+E&rft.aulast=Le+Fauve&rft.aufirst=Charlene&rft.date=2003-08-01&rft.volume=27&rft.issue=8&rft.spage=1318&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 - 2004-03-31 N1 - Date created - 2003-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Health disparities and the relationship between race, ethnicity, and substance abuse treatment outcomes. AN - 73630763; 12966330 JF - Alcoholism, clinical and experimental research AU - Lowman, Cherry AU - Le Fauve, Charlene E AD - National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Department of Health and Human Service, Bethesda, Maryland 20892-7003, USA. clowman@niaaa.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 1324 EP - 1326 VL - 27 IS - 8 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Humans KW - Treatment Outcome KW - Follow-Up Studies KW - Substance-Related Disorders -- therapy KW - European Continental Ancestry Group -- statistics & numerical data KW - Substance-Related Disorders -- ethnology KW - African Continental Ancestry Group -- statistics & numerical data KW - Health Services Accessibility -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73630763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Health+disparities+and+the+relationship+between+race%2C+ethnicity%2C+and+substance+abuse+treatment+outcomes.&rft.au=Lowman%2C+Cherry%3BLe+Fauve%2C+Charlene+E&rft.aulast=Lowman&rft.aufirst=Cherry&rft.date=2003-08-01&rft.volume=27&rft.issue=8&rft.spage=1324&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 - 2004-03-31 N1 - Date created - 2003-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of Xenopus tropicalis as an alternative test organism for frog embryo teratogenesis assay--Xenopus (FETAX). AN - 73614670; 12953658 AB - As a formal recommendation from an Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) workshop review of the Frog Embryo Teratogenesis Assay--Xenopus (FETAX) developmental toxicity model, the use of Xenopus tropicalis as an alternative test species for this model was evaluated. Three test substances with varying developmental toxicity potentials were evaluated using FETAX modified to accommodate the use of X. tropicalis. Two separate definitive concentration-response tests were performed with isoniazid, methotrexate, and 6-aminonicotinamide. Historical FETAX results with X. laevis were compared to the results from FETAX assays with X. tropicalis. Test with X. tropicalis indicated that each of the compounds possessed teratogenic potential with varying degrees of potency: 6-aminonicotinamide > methotrexate > isoniazid. Based on overt teratogenicity, but not embryo-lethality, results from these studies indicated that these two species responded similarly to the test compounds. Malformation syndromes induced in both species were similar in X. tropicalis and X. laevis. These results suggested that X. tropicalis should be further evaluated as an alternative test organism for the FETAX model. JF - Drug and chemical toxicology AU - Song, Min Ok AU - Fort, Douglas J AU - McLaughlin, Daniel L AU - Rogers, Robert L AU - Thomas, John H AU - Buzzard, Brody O AU - Noll, Andra M AU - Myers, Natalie K AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 177 EP - 189 VL - 26 IS - 3 SN - 0148-0545, 0148-0545 KW - Teratogens KW - 0 KW - 6-Aminonicotinamide KW - 329-89-5 KW - Isoniazid KW - V83O1VOZ8L KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Embryo, Nonmammalian -- abnormalities KW - 6-Aminonicotinamide -- toxicity KW - Isoniazid -- toxicity KW - Embryo, Nonmammalian -- drug effects KW - Methotrexate -- toxicity KW - Xenopus -- embryology KW - Abnormalities, Drug-Induced -- embryology KW - Toxicity Tests -- methods KW - Teratogens -- toxicity KW - Abnormalities, Drug-Induced -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73614670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+chemical+toxicology&rft.atitle=Evaluation+of+Xenopus+tropicalis+as+an+alternative+test+organism+for+frog+embryo+teratogenesis+assay--Xenopus+%28FETAX%29.&rft.au=Song%2C+Min+Ok%3BFort%2C+Douglas+J%3BMcLaughlin%2C+Daniel+L%3BRogers%2C+Robert+L%3BThomas%2C+John+H%3BBuzzard%2C+Brody+O%3BNoll%2C+Andra+M%3BMyers%2C+Natalie+K&rft.aulast=Song&rft.aufirst=Min&rft.date=2003-08-01&rft.volume=26&rft.issue=3&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Drug+and+chemical+toxicology&rft.issn=01480545&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-24 N1 - Date created - 2003-09-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Drug Chem Toxicol. 2004 Feb;27(1):93-4 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allogeneic stem cell transplantation as immunotherapy for renal cell carcinoma: from immune enhancement to immune replacement. AN - 73614613; 12953759 AB - The lack of efficacy of chemotherapeutics, radiotherapy, and cytokine-based immunotherapy has catalyzed the preliminary enthusiasm for nonmyeloablative stem cell transplants as a novel investigational tool for treating metastatic RCC. The observation that cytokine-refractory metastatic RCC may regress following allogeneic transplantation attests to the powerful nature of the graft-versus-tumor effect that results from this treatment modality. Pilot trials and recent in vitro data provide the first clear evidence that the graft-versus-tumor effect mounted against RCC can produce clinically meaningful regression of a metastatic solid tumor. Given this observation, the authors have begun to expand the investigational use of nonmyeloablative stem cell transplants to other treatment-refractory genitourinary tumors, including metastatic bladder and prostate cancer. It is hoped that future demonstrations of graft-versus-tumor effects in other solid malignancies will lay the groundwork for the development of tumor-targeted strategies that use allogeneic transplantation of donor lymphocytes as an immunotherapeutic platform. Further advances in systemic and selective immunosuppressive agents that limit acute GVHD hold the potential to decrease the toxicity associated with nonmyeloablative stem cell transplants and may ultimately broaden the clinical applicability of this approach. JF - The Urologic clinics of North America AU - Drachenberg, Darrel AU - Childs, Richard W AD - Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 611 EP - 622 VL - 30 IS - 3 SN - 0094-0143, 0094-0143 KW - Abridged Index Medicus KW - Index Medicus KW - Graft vs Tumor Effect -- immunology KW - Humans KW - Transplantation, Homologous KW - Immunotherapy -- methods KW - Stem Cell Transplantation -- methods KW - Kidney Neoplasms -- therapy KW - Carcinoma, Renal Cell -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73614613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Urologic+clinics+of+North+America&rft.atitle=Allogeneic+stem+cell+transplantation+as+immunotherapy+for+renal+cell+carcinoma%3A+from+immune+enhancement+to+immune+replacement.&rft.au=Drachenberg%2C+Darrel%3BChilds%2C+Richard+W&rft.aulast=Drachenberg&rft.aufirst=Darrel&rft.date=2003-08-01&rft.volume=30&rft.issue=3&rft.spage=611&rft.isbn=&rft.btitle=&rft.title=The+Urologic+clinics+of+North+America&rft.issn=00940143&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-25 N1 - Date created - 2003-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Separation of bivalent anti-T cell immunotoxin from Pichia pastoris glycoproteins by borate anion exchange. AN - 73609617; 12951782 AB - A major problem encountered in the large-scale purification of the bivalent anti-T cell immunotoxin, A-dmDT390-bisFv(G4S), from Pichia pastoris supernatants was the presence of host glycoproteins exhibiting similar charge, size, and hydrophobicity characteristics. We overcame this problem by employing borate anion exchange chromatography. The borate anion has an affinity for carbohydrates and imparts negative charges to these structures. We found that at a concentration of sodium borate between 50 and 100 mM, the nonglycosylated immunotoxin did not bind to Poros 50 HQ anion exchanger resin, but glycoproteins, including aggregates related to the immunotoxin, did. By using this property of the immunotoxin in the presence of sodium borate, we successfully developed a 3-step purification procedure: (i) Butyl-650M hydrophobic interaction chromatography, (ii) Poros 50 HQ anion exchange chromatography in the presence of borate, and (iii) HiTrap Q anion exchange chromatography. The final preparation exhibited a purity of greater than 98% and a yield of greater than 50% from the supernatant. Previously, boronic acid resins have been used to separate glycoproteins from proteins. However, combining borate anion with conventional anion exchange resins accomplishes the separation of the immunotoxin from glycoproteins and eliminates the need to evaluate nonstandard resins with respect to good manufacturing practice guidelines. JF - BioTechniques AU - Woo, Jung Hee AU - Neville, David M AD - National Institute of Mental Health, Bethesda, MD, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 392 EP - 398 VL - 35 IS - 2 SN - 0736-6205, 0736-6205 KW - Anion Exchange Resins KW - 0 KW - Borates KW - Glycoproteins KW - Immunotoxins KW - Index Medicus KW - Electrophoresis, Polyacrylamide Gel KW - Scintillation Counting KW - Humans KW - Jurkat Cells KW - Toxicity Tests KW - Chromatography, Ion Exchange KW - Immunotoxins -- chemistry KW - Immunotoxins -- toxicity KW - Pichia -- genetics KW - Glycoproteins -- isolation & purification KW - Borates -- chemistry KW - Immunotoxins -- isolation & purification KW - Immunotoxins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73609617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioTechniques&rft.atitle=Separation+of+bivalent+anti-T+cell+immunotoxin+from+Pichia+pastoris+glycoproteins+by+borate+anion+exchange.&rft.au=Woo%2C+Jung+Hee%3BNeville%2C+David+M&rft.aulast=Woo&rft.aufirst=Jung&rft.date=2003-08-01&rft.volume=35&rft.issue=2&rft.spage=392&rft.isbn=&rft.btitle=&rft.title=BioTechniques&rft.issn=07366205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-14 N1 - Date created - 2003-09-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of microarrays to characterize neuropsychiatric disorders: postmortem studies of substance abuse and schizophrenia. AN - 73600914; 12942997 AB - Neuropsychiatric disorders are generally diagnosed based on a classification of behavioral and, in some cases, specific neurological deficits. The lack of distinct quantitative and qualitative biological descriptors at the anatomical and cellular level complicates the search for and understanding of the neurobiology of these disorders. The advent of microarray technology has enabled large-scale profiling of transcriptional activity, allowing a comprehensive characterization of transcriptional patterns relating to the pathophysiology of neuropsychiatric disorders. We review some of the unique methodological constraints related to the use of human postmortem brain tissue in addition to the generally applicable requirements for microarray experiments. Microarray studies undertaken in neuropsychiatric disorders such as schizophrenia and substance abuse by the use of postmortem brain tissue indicate that transcriptional changes relating to synaptic function and plasticity, cytoskeletal function, energy metabolism, oligodendrocytes, and distinct intracellular signaling pathways are generally present. These have been supported by microarray studies in experimental models, and have produced multiple avenues to be explored at the functional level. The quality and specificity of information obtained from human postmortem tissue is rapidly increasing with the maturation and refinement of array-related methodologies and analysis tools, and with the use of focused cell populations. The development of experimental models of gene regulation in these disorders will serve as the initial step towards a comprehensive genome-linked analysis of the brain and associated disorders, and help characterize the integration and coordinate regulation of complex functions within the CNS. JF - Current molecular medicine AU - Lehrmann, E AU - Hyde, T M AU - Vawter, M P AU - Becker, K G AU - Kleinman, J E AU - Freed, W J AD - Cellular Neurobiology Research Branch, National Institute on Drug Abuse, NIH/DHHS, Baltimore, MD 21224, USA. elehrman@intra.nida.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 437 EP - 446 VL - 3 IS - 5 SN - 1566-5240, 1566-5240 KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Gene Expression Profiling KW - RNA -- metabolism KW - Humans KW - Myelin Sheath -- metabolism KW - Synapses -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Schizophrenia -- metabolism KW - Substance-Related Disorders -- metabolism KW - Schizophrenia -- genetics KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73600914?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+molecular+medicine&rft.atitle=The+use+of+microarrays+to+characterize+neuropsychiatric+disorders%3A+postmortem+studies+of+substance+abuse+and+schizophrenia.&rft.au=Lehrmann%2C+E%3BHyde%2C+T+M%3BVawter%2C+M+P%3BBecker%2C+K+G%3BKleinman%2C+J+E%3BFreed%2C+W+J&rft.aulast=Lehrmann&rft.aufirst=E&rft.date=2003-08-01&rft.volume=3&rft.issue=5&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Current+molecular+medicine&rft.issn=15665240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-26 N1 - Date created - 2003-08-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Do noncontingent vouchers increase drug use? AN - 73584678; 12940498 AB - Data from 2 contingency management trials, targeting opiate or cocaine use, were used to investigate whether noncontingent vouchers inadvertently reinforce drug use. The control group in each trial received noncontingent vouchers matched in value and frequency to those received by experimental groups, but independent of urinalysis. Vouchers were offered thrice weekly for 8 weeks (opiates) or 12 weeks (cocaine). Both dose-response and temporal associations of noncontingent voucher receipt with drug-positive urines were assessed. Drug use was unrelated to frequency of noncontingent voucher delivery and noncontingent voucher receipt when being drug positive was unassociated with risk of subsequent drug use, with one exception: cocaine use in the cocaine study (relative risk = 1.05, 95% confidence interval: 1.01-1.09). Overall, results do not indicate a causal relationship between noncontingent voucher receipt and increased drug use. JF - Experimental and clinical psychopharmacology AU - Schroeder, Jennifer R AU - Gupman, Anne E AU - Epstein, David H AU - Umbricht, Annie AU - Preston, Kenzie L AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. jschroed@intra.nida.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 195 EP - 201 VL - 11 IS - 3 SN - 1064-1297, 1064-1297 KW - Narcotics KW - 0 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Methadone -- therapeutic use KW - Dose-Response Relationship, Drug KW - Humans KW - Recurrence KW - Risk Assessment KW - Psychiatric Status Rating Scales KW - Logistic Models KW - Substance Abuse Detection KW - Adult KW - Treatment Outcome KW - Narcotics -- therapeutic use KW - Female KW - Male KW - Opioid-Related Disorders -- psychology KW - Cocaine-Related Disorders -- psychology KW - Opioid-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- urine KW - Opioid-Related Disorders -- urine KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- psychology KW - Cocaine-Related Disorders -- rehabilitation KW - Cocaine-Related Disorders -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73584678?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Do+noncontingent+vouchers+increase+drug+use%3F&rft.au=Schroeder%2C+Jennifer+R%3BGupman%2C+Anne+E%3BEpstein%2C+David+H%3BUmbricht%2C+Annie%3BPreston%2C+Kenzie+L&rft.aulast=Schroeder&rft.aufirst=Jennifer&rft.date=2003-08-01&rft.volume=11&rft.issue=3&rft.spage=195&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 - 2003-11-21 N1 - Date created - 2003-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diminished expression of an antiviral ribonuclease in response to pneumovirus infection in vivo. AN - 73580650; 12927308 AB - The mouse eosinophil-associated ribonucleases (mEars) are species specific, divergent orthologs of the human antiviral RNase A ribonucleases, eosinophil-derived neurotoxin (RNase 2) and eosinophil cationic protein (RNase 3). We show here that mEar 2 is also an antiviral ribonuclease, as micromolar concentrations promote a approximately sixfold reduction in the infectivity of pneumonia virus of mice (PVM) for target respiratory epithelial cells in vitro. Although initially identified as a component of eosinophilic leukocytes, mEar 2 mRNA and protein were also detected in lung tissue accompanied by enzymatically active mEar 2 in bronchoalveolar lavage fluid (BALF). At t=3 days post-inoculation with PVM (strain J3666), we observed the characteristic inflammatory response accompanied by diminished expression of total mEar mRNA and protein in lung tissue and a corresponding fivefold drop in ribonuclease activity in BALF. No change in mEar expression was observed in response to infection with PVM strain 15, a replication-competent strain of PVM that does not elicit a cellular inflammatory response. However, mEar expression is not directly dependent on inflammation per se, as diminished expression of mEar mRNA and BAL ribonuclease activity were also observed in PVM-infected, inflammation-deficient, MIP-1alpha -/- mice. We propose that this mechanism may represent a novel virus-mediated evasion strategy, with a mechanism that is linked in some fashion to virus-specific pathogenicity. JF - Antiviral research AU - Moreau, Joanne M AU - Dyer, Kimberly D AU - Bonville, Cynthia A AU - Nitto, Takeaki AU - Vasquez, Nora L AU - Easton, Andrew J AU - Domachowske, Joseph B AU - Rosenberg, Helene F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N104, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 181 EP - 191 VL - 59 IS - 3 SN - 0166-3542, 0166-3542 KW - Antiviral Agents KW - 0 KW - RNA, Messenger KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Lung -- immunology KW - Bronchoalveolar Lavage Fluid -- immunology KW - Animals KW - RNA, Messenger -- metabolism KW - Mice KW - Lung -- enzymology KW - Inflammation -- immunology KW - Pneumovirus Infections -- physiopathology KW - Murine pneumonia virus -- pathogenicity KW - Pneumovirus Infections -- virology KW - Eosinophils -- enzymology KW - Ribonucleases -- genetics KW - Antiviral Agents -- metabolism KW - Ribonucleases -- metabolism KW - Eosinophils -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73580650?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Diminished+expression+of+an+antiviral+ribonuclease+in+response+to+pneumovirus+infection+in+vivo.&rft.au=Moreau%2C+Joanne+M%3BDyer%2C+Kimberly+D%3BBonville%2C+Cynthia+A%3BNitto%2C+Takeaki%3BVasquez%2C+Nora+L%3BEaston%2C+Andrew+J%3BDomachowske%2C+Joseph+B%3BRosenberg%2C+Helene+F&rft.aulast=Moreau&rft.aufirst=Joanne&rft.date=2003-08-01&rft.volume=59&rft.issue=3&rft.spage=181&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 - 2003-11-10 N1 - Date created - 2003-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Is inducible nitric oxide synthase a target for chemoprevention? AN - 73571563; 12939472 AB - The molecular messenger nitric oxide (NO) is synthesized endogenously from L-arginine by three isoforms of the enzyme NO synthase. The isoform most consistently associated with neoplasia is the inducible form, inducible nitric oxide synthase (iNOS). However, the role played by the NO/iNOS system in tumor development is complex, and both promoting and inhibitory effects on neoplasia have been reported. This review attempts to clarify the role of iNOS in carcinogenesis, with particular emphasis on the early stages of tumor development, offers possible explanations for the confused picture presented in the literature regarding the association of the NO/iNOS pathway with neoplasia, and identifies selective iNOS inhibitors that may have chemopreventive potential. JF - Molecular cancer therapeutics AU - Crowell, James A AU - Steele, Vernon E AU - Sigman, Caroline C AU - Fay, Judith R AD - National Cancer Institute, Division of Cancer Prevention, Chemopreventive Agent Development Research Group, Bethesda, Maryland 20892, USA. jcrowell@mail.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 815 EP - 823 VL - 2 IS - 8 SN - 1535-7163, 1535-7163 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Index Medicus KW - Animals KW - Nitric Oxide Synthase -- physiology KW - Chemoprevention UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73571563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cancer+therapeutics&rft.atitle=Is+inducible+nitric+oxide+synthase+a+target+for+chemoprevention%3F&rft.au=Crowell%2C+James+A%3BSteele%2C+Vernon+E%3BSigman%2C+Caroline+C%3BFay%2C+Judith+R&rft.aulast=Crowell&rft.aufirst=James&rft.date=2003-08-01&rft.volume=2&rft.issue=8&rft.spage=815&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+therapeutics&rft.issn=15357163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-21 N1 - Date created - 2003-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiation doses in interventional radiology procedures: the RAD-IR study: part II: skin dose. AN - 73563242; 12902555 AB - To determine peak skin dose (PSD), a measure of the likelihood of radiation-induced skin effects, for a variety of common interventional radiology and interventional neuroradiology procedures, and to identify procedures associated with a PSD greater than 2 Gy. An observational study was conducted at seven academic medical centers in the United States. Sites prospectively contributed demographic and radiation dose data for subjects undergoing 21 specific procedures in a fluoroscopic suite equipped with built-in dosimetry capability. Comprehensive physics evaluations and periodic consistency checks were performed on each unit to verify the stability and consistency of the dosimeter. Seven of 12 fluoroscopic suites in the study were equipped with skin dose mapping software. Over a 3-year period, skin dose data were recorded for 800 instances of 21 interventional radiology procedures. Wide variation in PSD was observed for different instances of the same procedure. Some instances of each procedure we studied resulted in a PSD greater than 2 Gy, except for nephrostomy, pulmonary angiography, and inferior vena cava filter placement. Some instances of transjugular intrahepatic portosystemic shunt (TIPS) creation, renal/visceral angioplasty, and angiographic diagnosis and therapy of gastrointestinal hemorrhage produced PSDs greater than 3 Gy. Some instances of hepatic chemoembolization, other tumor embolization, and neuroembolization procedures in the head and spine produced PSDs greater than 5 Gy. In a subset of 709 instances of higher-dose procedures, there was good overall correlation between PSD and cumulative dose (r = 0.86; P <.000001) and between PSD and dose-area-product (r = 0.85, P <.000001), but there was wide variation in these relationships for individual instances. There are substantial variations in PSD among instances of the same procedure and among different procedure types. Most of the procedures observed may produce a PSD sufficient to cause deterministic effects in skin. It is suggested that dose data be recorded routinely for TIPS creation, angioplasty in the abdomen or pelvis, all embolization procedures, and especially for head and spine embolization procedures. Measurement or estimation of PSD is the best method for determining the likelihood of radiation-induced skin effects. Skin dose mapping is preferable to a single-point measurement of PSD. JF - Journal of vascular and interventional radiology : JVIR AU - Miller, Donald L AU - Balter, Stephen AU - Cole, Patricia E AU - Lu, Hollington T AU - Berenstein, Alejandro AU - Albert, Robin AU - Schueler, Beth A AU - Georgia, Jeffrey D AU - Noonan, Patrick T AU - Russell, Eric J AU - Malisch, Tim W AU - Vogelzang, Robert L AU - Geisinger, Michael AU - Cardella, John F AU - George, James St AU - Miller, George L AU - Anderson, Jon AD - Department of Radiology, National Naval Medical Center, Bethesda, MD 20889-5600, USA. dm72v@nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 977 EP - 990 VL - 14 IS - 8 SN - 1051-0443, 1051-0443 KW - Index Medicus KW - Software KW - Prospective Studies KW - Radiometry KW - Humans KW - Neuroradiography KW - Fluoroscopy KW - Radiation Dosage KW - Skin -- radiation effects KW - Radiation Protection KW - Radiology, Interventional UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73563242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+vascular+and+interventional+radiology+%3A+JVIR&rft.atitle=Radiation+doses+in+interventional+radiology+procedures%3A+the+RAD-IR+study%3A+part+II%3A+skin+dose.&rft.au=Miller%2C+Donald+L%3BBalter%2C+Stephen%3BCole%2C+Patricia+E%3BLu%2C+Hollington+T%3BBerenstein%2C+Alejandro%3BAlbert%2C+Robin%3BSchueler%2C+Beth+A%3BGeorgia%2C+Jeffrey+D%3BNoonan%2C+Patrick+T%3BRussell%2C+Eric+J%3BMalisch%2C+Tim+W%3BVogelzang%2C+Robert+L%3BGeisinger%2C+Michael%3BCardella%2C+John+F%3BGeorge%2C+James+St%3BMiller%2C+George+L%3BAnderson%2C+Jon&rft.aulast=Miller&rft.aufirst=Donald&rft.date=2003-08-01&rft.volume=14&rft.issue=8&rft.spage=977&rft.isbn=&rft.btitle=&rft.title=Journal+of+vascular+and+interventional+radiology+%3A+JVIR&rft.issn=10510443&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-21 N1 - Date created - 2003-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinguishing right from left colon by the pattern of gene expression. AN - 73555492; 12917207 AB - Distinct epidemiological and clinicopathological characteristics of colorectal carcinomas (CRCs) based on their anatomical location suggest different risk factors and pathways of transformation associated with proximal and distal colon carcinogenesis. These differences may reflect distinct biological characteristics of proximal and distal colonic mucosa, acquired in embryonic or postnatal development, that determine a differential response to uniformly distributed environmental factors. Alternatively, the differences in the epidemiology of proximal and distal CRCs could result from the presence of different procarcinogenic factors in the ascending versus descending colon, acting on cells with either similar or distinct biological characteristics. We applied cDNA microarray technology to explore the possibility that mucosal epithelium from adult proximal and distal colon can be distinguished by their pattern of gene expression. In addition, gene expression was studied in fetal (17-24 weeks gestation) proximal and distal colon. More than 1000 genes were expressed differentially in adult ascending versus descending colon, with 165 genes showing >2-fold and 49 genes showing >3-fold differences in expression. With almost complete concordance, biopsies of adult colonic epithelium can be correctly classified as proximal or distal by gene expression profile. Only 87 genes were expressed differently in ascending and descending fetal colon, indicating that, although anatomically relevant differences are already established in embryonic colon, additional changes in gene expression occur in postnatal development. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Glebov, Oleg K AU - Rodriguez, Luz M AU - Nakahara, Kenneth AU - Jenkins, Jean AU - Cliatt, Janet AU - Humbyrd, Casey-Jo AU - DeNobile, John AU - Soballe, Peter AU - Simon, Richard AU - Wright, George AU - Lynch, Patrick AU - Patterson, Sherri AU - Lynch, Henry AU - Gallinger, Steven AU - Buchbinder, Aby AU - Gordon, Gary AU - Hawk, Ernest AU - Kirsch, Ilan R AD - Genetics Branch, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, Maryland 20892, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 755 EP - 762 VL - 12 IS - 8 SN - 1055-9965, 1055-9965 KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Adult KW - RNA -- analysis KW - Colon -- embryology KW - Functional Laterality KW - Gene Amplification KW - Colon, Descending KW - Colon, Ascending KW - Gene Expression -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73555492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Distinguishing+right+from+left+colon+by+the+pattern+of+gene+expression.&rft.au=Glebov%2C+Oleg+K%3BRodriguez%2C+Luz+M%3BNakahara%2C+Kenneth%3BJenkins%2C+Jean%3BCliatt%2C+Janet%3BHumbyrd%2C+Casey-Jo%3BDeNobile%2C+John%3BSoballe%2C+Peter%3BSimon%2C+Richard%3BWright%2C+George%3BLynch%2C+Patrick%3BPatterson%2C+Sherri%3BLynch%2C+Henry%3BGallinger%2C+Steven%3BBuchbinder%2C+Aby%3BGordon%2C+Gary%3BHawk%2C+Ernest%3BKirsch%2C+Ilan+R&rft.aulast=Glebov&rft.aufirst=Oleg&rft.date=2003-08-01&rft.volume=12&rft.issue=8&rft.spage=755&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 - 2003-12-09 N1 - Date created - 2003-08-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Susceptibility to aflatoxin B1-related primary hepatocellular carcinoma in mice and humans. AN - 73547410; 12907637 AB - The genetic basis of disease susceptibility can be studied by several means, including research on animal models and epidemiological investigations in humans. The two methods are infrequently used simultaneously, but their joint use may overcome the disadvantages of either method alone. We used both approaches in an attempt to understand the genetic basis of aflatoxin B(1) (AFB(1))-related susceptibility to hepatocellular carcinoma (HCC). Ingestion of AFB(1) is a major risk factor for HCC in many areas of the world where HCC is common. Whether humans vary in their ability to detoxify the active intermediate metabolite of AFB(1), AFB(1)-exo-8,9-epoxide, is not certain but may explain why all exposed individuals do not develop HCC. To determine whether human variability in detoxification may exist, in a study of 231 HCC cases and 256 controls, we genotyped eleven loci in two families of AFB(1) detoxification genes; the glutathione S-transferases (GSTs) and the epoxide hydrolases (EPHX). After adjustment for multiple comparisons, only one polymorphism in the epoxide hydrolase family 2 locus remained significantly associated with HCC (odds ratio = 2.06, 95% confidence interval = 1.13-3.12). To determine whether additional susceptibility loci exist, we developed a mouse model system to examine AFB(1)-induced HCC. Susceptibility of 7-day-old mice from two common inbred strains (C57BL/6J, DBA/2J) was assessed. DBA/2J animals were 3-fold more sensitive to AFB(1)-induced HCC and significantly more sensitive to AFB(1) acute toxicity than were C57BL/6J animals. Analysis of the xenobiotic metabolizing genes in the two strains revealed single nucleotide polymorphisms in three genes, Gsta4, Gstt1, and Ephx1. Although the GSTT1 and EPHX1 loci did not appear to be related to HCC in the total population of the human study, a polymorphism in GSTA4 was significantly related to risk in the male subset. The mouse model also demonstrated that absent or compromised p53 was not necessary for the development of carcinogenesis. These results indicate that the comparison of results from human studies and the AFB(1)-susceptible mouse model may provide new insights into hepatocarcinogenesis. JF - Cancer research AU - McGlynn, Katherine A AU - Hunter, Kent AU - LeVoyer, Thomas AU - Roush, Jessica AU - Wise, Philip AU - Michielli, Rita A AU - Shen, Fu-Min AU - Evans, Alison A AU - London, W Thomas AU - Buetow, Kenneth H AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH/DHHS, 6120 Executive Boulevard, Bethesda, MD 20892, USA. Y1 - 2003/08/01/ PY - 2003 DA - 2003 Aug 01 SP - 4594 EP - 4601 VL - 63 IS - 15 SN - 0008-5472, 0008-5472 KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Index Medicus KW - Animals KW - Liver Neoplasms, Experimental -- genetics KW - Humans KW - Liver Neoplasms, Experimental -- chemically induced KW - Amino Acid Sequence KW - Mice KW - Mice, Transgenic KW - Mice, Knockout KW - Mice, Inbred DBA KW - Conserved Sequence KW - Molecular Sequence Data KW - Case-Control Studies KW - Mice, Inbred C57BL KW - Middle Aged KW - Female KW - Male KW - Aflatoxin B1 -- adverse effects KW - Cocarcinogenesis KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- chemically induced KW - Carcinoma, Hepatocellular -- chemically induced KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73547410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Susceptibility+to+aflatoxin+B1-related+primary+hepatocellular+carcinoma+in+mice+and+humans.&rft.au=McGlynn%2C+Katherine+A%3BHunter%2C+Kent%3BLeVoyer%2C+Thomas%3BRoush%2C+Jessica%3BWise%2C+Philip%3BMichielli%2C+Rita+A%3BShen%2C+Fu-Min%3BEvans%2C+Alison+A%3BLondon%2C+W+Thomas%3BBuetow%2C+Kenneth+H&rft.aulast=McGlynn&rft.aufirst=Katherine&rft.date=2003-08-01&rft.volume=63&rft.issue=15&rft.spage=4594&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 - 2003-09-23 N1 - Date created - 2003-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - POS5 gene of Saccharomyces cerevisiae encodes a mitochondrial NADH kinase required for stability of mitochondrial DNA. AN - 73547109; 12912900 AB - In a search for nuclear genes that affect mutagenesis of mitochondrial DNA in Saccharomyces cerevisiae, an ATP-NAD (NADH) kinase, encoded by POS5, that functions exclusively in mitochondria was identified. The POS5 gene product was overproduced in Escherichia coli and purified without a mitochondrial targeting sequence. A direct biochemical assay demonstrated that the POS5 gene product utilizes ATP to phosphorylate both NADH and NAD(+), with a twofold preference for NADH. Disruption of POS5 increased minus-one frameshift mutations in mitochondrial DNA 50-fold, as measured by the arg8(m) reversion assay, with no increase in nuclear mutations. Also, a dramatic increase in petite colony formation and slow growth on glycerol or limited glucose were observed. POS5 was previously described as a gene required for resistance to hydrogen peroxide. Consistent with a role in the mitochondrial response to oxidative stress, a pos5 deletion exhibited a 28-fold increase in oxidative damage to mitochondrial proteins and hypersensitivity to exogenous copper. Furthermore, disruption of POS5 induced mitochondrial biogenesis as a response to mitochondrial dysfunction. Thus, the POS5 NADH kinase is required for mitochondrial DNA stability with a critical role in detoxification of reactive oxygen species. These results predict a role for NADH kinase in human mitochondrial diseases. JF - Eukaryotic cell AU - Strand, Micheline K AU - Stuart, Gregory R AU - Longley, Matthew J AU - Graziewicz, Maria A AU - Dominick, Olivia C AU - Copeland, William C AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 809 EP - 820 VL - 2 IS - 4 SN - 1535-9778, 1535-9778 KW - DNA, Mitochondrial KW - 0 KW - Mitochondrial Proteins KW - Reactive Oxygen Species KW - Saccharomyces cerevisiae Proteins KW - NAD KW - 0U46U6E8UK KW - Copper KW - 789U1901C5 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Phosphotransferases (Alcohol Group Acceptor) KW - EC 2.7.1.- KW - POS5 protein, S cerevisiae KW - EC 2.7.1.86 KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Mitochondrial Diseases -- genetics KW - Energy Metabolism -- genetics KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Oxidative Stress -- genetics KW - Copper -- pharmacology KW - Mitochondrial Diseases -- enzymology KW - Phosphorylation KW - Cells, Cultured KW - Adenosine Triphosphate -- metabolism KW - Mutation -- genetics KW - Saccharomyces cerevisiae Proteins -- physiology KW - Saccharomyces cerevisiae -- genetics KW - Saccharomyces cerevisiae Proteins -- genetics KW - Phosphotransferases (Alcohol Group Acceptor) -- isolation & purification KW - Mitochondria -- enzymology KW - Phosphotransferases (Alcohol Group Acceptor) -- physiology KW - Saccharomyces cerevisiae -- enzymology KW - Phosphotransferases (Alcohol Group Acceptor) -- genetics KW - Mitochondria -- genetics KW - Saccharomyces cerevisiae Proteins -- isolation & purification KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73547109?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Eukaryotic+cell&rft.atitle=POS5+gene+of+Saccharomyces+cerevisiae+encodes+a+mitochondrial+NADH+kinase+required+for+stability+of+mitochondrial+DNA.&rft.au=Strand%2C+Micheline+K%3BStuart%2C+Gregory+R%3BLongley%2C+Matthew+J%3BGraziewicz%2C+Maria+A%3BDominick%2C+Olivia+C%3BCopeland%2C+William+C&rft.aulast=Strand&rft.aufirst=Micheline&rft.date=2003-08-01&rft.volume=2&rft.issue=4&rft.spage=809&rft.isbn=&rft.btitle=&rft.title=Eukaryotic+cell&rft.issn=15359778&rft_id=info:doi/ LA - 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Last updated - 2017-01-18 ER - TY - JOUR T1 - Biodistribution, radiation dose estimates, and in vivo Pgp modulation studies of 18F-paclitaxel in nonhuman primates. AN - 73546576; 12902425 AB - Multidrug resistance (MDR) associated with increased expression and function of the P-glycoprotein (Pgp) efflux pump often causes chemotherapeutic failure in cancer. To provide insight into both the dynamics of the pump and the effects of MDR, we radiolabeled paclitaxel, a substrate for the Pgp pump, with (18)F to study MDR in vivo with PET. We obtained biodistribution and radiation dose estimates for (18)F-paclitaxel (FPAC) in monkeys and studied the effects of a Pgp blocker (XR9576, tariquidar) on FPAC kinetics. Paired baseline and Pgp modulation (2 mg/kg XR9576) 4-h whole-body dynamic PET scans were obtained in 3 rhesus monkeys after injection of FPAC. Measured residence times were extrapolated to humans and radiation dose estimates were obtained using MIRDOSE3.1. The postmodulator area under the time-activity curves (AUCs) and Logan plot slopes, a measure of tracer distribution volume (equilibrium tissue-to-plasma ratio) that is inversely proportional to tracer efflux, were compared with baseline values to determine changes in FPAC distribution. Cumulative activities of the organs sampled accounted for 80% of the injected dose. The critical organ is gallbladder wall (0.19 mGy/MBq [0.69 rad/mCi]), followed by liver (0.14 mGy/MBq [0.52 rad/mCi]); the effective dose is 0.022 mSv/MBq (0.083 rem/mCi). XR9576 preinfusion changed the Logan plot slope for liver by +104% (P = 0.02), lung by +87% (P = 0.11), and kidney by -14% (P = 0.08). Changes in the mean AUC (normalized to the plasma AUC) were +54% (P = 0.08), +97% (P = 0.04), and -12% (P = 0.02), respectively, for liver, lung, and kidney. No significant difference was found in the metabolite-corrected plasma AUC (normalized to the injected dose) between the baseline and XR9576 modulator studies (P = 0.69). Under Radioactive Drug Research Committee guidelines, 266 MBq (7.2 mCi) FPAC can be administered to humans up to 3 times a year. The increase in FPAC accumulation in liver and lung after XR9576 is consistent with Pgp inhibition and demonstrates the potential of FPAC to evaluate MDR. JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine AU - Kurdziel, Karen A AU - Kiesewetter, Dale O AU - Carson, Richard E AU - Eckelman, William C AU - Herscovitch, Peter AD - PET Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA. kurdziel@hsc.vcu.edu Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 1330 EP - 1339 VL - 44 IS - 8 SN - 0161-5505, 0161-5505 KW - P-Glycoprotein KW - 0 KW - Quinolines KW - tariquidar KW - J58862DTVD KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Radiation Dosage KW - Whole-Body Counting -- methods KW - Humans KW - Metabolic Clearance Rate KW - Organ Specificity KW - Tissue Distribution KW - Primates KW - Isotope Labeling -- methods KW - Macaca mulatta KW - Radiometry -- methods KW - Female KW - Male KW - Paclitaxel -- blood KW - P-Glycoprotein -- metabolism KW - Drug Resistance, Multiple -- physiology KW - Paclitaxel -- pharmacokinetics KW - Paclitaxel -- chemical synthesis KW - Paclitaxel -- analogs & derivatives KW - Quinolines -- pharmacokinetics KW - P-Glycoprotein -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73546576?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.atitle=Biodistribution%2C+radiation+dose+estimates%2C+and+in+vivo+Pgp+modulation+studies+of+18F-paclitaxel+in+nonhuman+primates.&rft.au=Kurdziel%2C+Karen+A%3BKiesewetter%2C+Dale+O%3BCarson%2C+Richard+E%3BEckelman%2C+William+C%3BHerscovitch%2C+Peter&rft.aulast=Kurdziel&rft.aufirst=Karen&rft.date=2003-08-01&rft.volume=44&rft.issue=8&rft.spage=1330&rft.isbn=&rft.btitle=&rft.title=Journal+of+nuclear+medicine+%3A+official+publication%2C+Society+of+Nuclear+Medicine&rft.issn=01615505&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-06 N1 - Date created - 2003-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kainic acid lesion-induced nigral neuronal death. AN - 73542389; 12954531 AB - Parkinson's disease (PD) is characterized by progressive death of dopamine (DA) neurons in the substantia nigra pars compacta. We report a rat model that exhibits progressive death of nigral neurons following unilateral injection of kainic acid in the striatum. In situ end-labeling revealed significant numbers of dying nigral neurons ipsilateral to the lesion during the first 3 weeks following injection. An indication of the gradual nature of death was that similar small numbers of cells were detected at each time point. These early morphological markers of neuronal death led to a significant reduction (20%) at 5 months of tyrosine hydroxylase-positive neurons and total number of neurons in the ipsilateral substantia nigra compared with the contralateral control. To examine the role of nigrostriatal DA metabolism in the observed nigral neuronal death, we manipulated DA metabolism during the initial 2 weeks following kainic acid lesion. Neurons in the ventral tier of the substantia nigra pars compacta were protected from death by treatment with 2,4-diamino-6-hydroxy-pyrimidine (DAHP), an inhibitor of GTP cyclohydrolase, the initial enzyme in the synthesis of the tyrosine hydroxylase co-substrate, tetrahydrobiopterin (BH(4)). Neurons in both the dorsal and ventral tier of substantia nigra pars compacta were protected from death by treatment with DAHP and L-DOPA. These experiments suggest that intrastriatal kainic acid lesion is an in vivo model of trophic support withdrawal. This experimental procedure is useful for studying mechanisms underlying protracted death of nigral DA neurons and may provide valuable mechanistic information relevant to understanding the etiology of PD. JF - Journal of chemical neuroanatomy AU - Foster, Jane A AU - Bezin, Laurent AU - Groc, Laurent AU - Christopherson, Patricia L AU - Levine, Robert A AD - William T. Gossett Neurology Laboratories, Henry Ford Health System, 1 Ford Place, 4D, Detroit, MI 48202, USA. jaf@codon.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 65 EP - 73 VL - 26 IS - 1 SN - 0891-0618, 0891-0618 KW - Enzyme Inhibitors KW - 0 KW - Excitatory Amino Acid Agonists KW - Biopterin KW - 22150-76-1 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - sapropterin KW - EGX657432I KW - Kainic Acid KW - SIV03811UC KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Tyrosine 3-Monooxygenase -- metabolism KW - Dopamine -- pharmacology KW - Substantia Nigra -- drug effects KW - Disease Models, Animal KW - Dopamine -- metabolism KW - Injections, Intraventricular KW - Rats KW - In Situ Nick-End Labeling KW - Rats, Sprague-Dawley KW - Substantia Nigra -- pathology KW - Enzyme Inhibitors -- pharmacology KW - Immunohistochemistry KW - Functional Laterality KW - Male KW - Kainic Acid -- administration & dosage KW - Biopterin -- analogs & derivatives KW - Cell Death -- physiology KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Excitatory Amino Acid Agonists -- administration & dosage KW - Excitatory Amino Acid Agonists -- toxicity KW - Biopterin -- metabolism KW - Parkinsonian Disorders -- pathology KW - Kainic Acid -- toxicity KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73542389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemical+neuroanatomy&rft.atitle=Kainic+acid+lesion-induced+nigral+neuronal+death.&rft.au=Foster%2C+Jane+A%3BBezin%2C+Laurent%3BGroc%2C+Laurent%3BChristopherson%2C+Patricia+L%3BLevine%2C+Robert+A&rft.aulast=Foster&rft.aufirst=Jane&rft.date=2003-08-01&rft.volume=26&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Journal+of+chemical+neuroanatomy&rft.issn=08910618&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-06 N1 - Date created - 2003-09-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The antioxidant conundrum in cancer. AN - 73535891; 12907593 AB - The health-related effects of interactions between reactive oxygen species (ROS) and dietary antioxidants and the consequences of dietary antioxidant supplementation on human health are by no means clear. Although ROS, normal byproducts of aerobic metabolism, are essential for various defense mechanisms in most cells, they can also cause oxidative damage to DNA, proteins, and lipids, resulting in enhanced disease risk. Dietary antioxidants (e.g., vitamin E, vitamin C, beta-carotene, and selenium), as well as endogenous antioxidant mechanisms, can help maintain an appropriate balance between the desirable and undesirable cellular effects of ROS. However, any health-related effects of interactions between dietary antioxidants and ROS likely depend on the health status of an individual and may also be influenced by genetic susceptibilities. Clinical studies of antioxidant supplementation and changes in either oxidative status, disease risk, or disease outcome have been carried out in healthy individuals, populations at risk for certain diseases, and patients undergoing disease therapy. The use of antioxidants during cancer therapy is currently a topic of heated debate because of an overall lack of clear research findings. Some data suggest antioxidants can ameliorate toxic side effects of therapy without affecting treatment efficacy, whereas other data suggest antioxidants interfere with radiotherapy or chemotherapy. Overall, examination of the evidence related to potential interactions between ROS and dietary antioxidants and effects on human health indicates that consuming dietary antioxidant supplements has pros and cons for any population and raises numerous questions, issues, and challenges that make this topic a fertile field for future research. Overall, current knowledge makes it premature to generalize and make specific recommendations about antioxidant usage for those at high risk for cancer or undergoing treatment. JF - Cancer research AU - Seifried, Harold E AU - McDonald, Sharon S AU - Anderson, Darrell E AU - Greenwald, Peter AU - Milner, John A AD - Division of Cancer Prevention, National Cancer Institute/NIH, 6130 Executive Boulevard, Suite 3160, Bethesda, MD 20852, USA. hs41s@nih.gov Y1 - 2003/08/01/ PY - 2003 DA - 2003 Aug 01 SP - 4295 EP - 4298 VL - 63 IS - 15 SN - 0008-5472, 0008-5472 KW - Antioxidants KW - 0 KW - Reactive Oxygen Species KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Reactive Oxygen Species -- adverse effects KW - Humans KW - Dietary Supplements -- adverse effects KW - Neoplasms -- drug therapy KW - Antioxidants -- adverse effects KW - Antioxidants -- pharmacology KW - Neoplasms -- prevention & control KW - Antioxidants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73535891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+antioxidant+conundrum+in+cancer.&rft.au=Seifried%2C+Harold+E%3BMcDonald%2C+Sharon+S%3BAnderson%2C+Darrell+E%3BGreenwald%2C+Peter%3BMilner%2C+John+A&rft.aulast=Seifried&rft.aufirst=Harold&rft.date=2003-08-01&rft.volume=63&rft.issue=15&rft.spage=4295&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 - 2003-09-23 N1 - Date created - 2003-08-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of mitochondrial K+ release and cellular efflux in ischemic and apoptotic neuronal death. AN - 73528293; 12887694 AB - We measured and manipulated intracellular potassium (K+) fluxes in cultured hippocampal neurons in an effort to understand the involvement of K+ in neuronal death under conditions of ischemia and exposure to apoptotic stimuli. Measurements of the intracellular K+ concentration using the fluorescent probe 1,3-benzenedicarboxylic acid, 4,4'-[1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-7,16-diylbis(5-methoxy-6,2-benzofurandiyl)]bis-, tetrakis [(acetyloxy) methyl] ester (PBFI) revealed that exposure of neurons to cyanide (chemical hypoxia), glutamate (excitotoxic insult) or staurosporine (apoptotic stimulus) results in efflux of K+ and cell death. Treatment of neurons with 5-hydroxydecanoate (5HD), an inhibitor of mitochondrial K+ channels, reduced K+ fluxes in neurons exposed to each insult and increased the resistance of the cells to death. K+ efflux was attenuated, levels of oxyradicals were decreased, mitochondrial membrane potential was stabilized and release of cytochrome c from mitochondria was attenuated in neurons treated with 5HD. K+ was rapidly released into the cytosol from mitochondria when neurons were exposed to the K+ channel opener, diazoxide, or to the mitochondrial uncoupler, carbonyl cyanide 4(trifluoromethoxy)phenylhydrazone (FCCP), demonstrating that the intramitochondrial K+ concentration is greater than the cytosolic K+ concentration. The release of K+ from mitochondria was followed by efflux through plasma membrane K+ channels. In vivo studies showed that 5HD reduces ischemic brain damage without affecting cerebral blood flow in a mouse model of focal ischemic stroke. These findings suggest that intracellular K+ fluxes play a key role in modulating neuronal oxyradical production and cell survival under ischemic conditions, and that agents that modify K+ fluxes may have therapeutic benefit in stroke and related neurodegenerative conditions. JF - Journal of neurochemistry AU - Liu, Dong AU - Slevin, John R AU - Lu, Chengbiao AU - Chan, Sic L AU - Hansson, Magnus AU - Elmér, Eskil AU - Mattson, Mark P AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 966 EP - 979 VL - 86 IS - 4 SN - 0022-3042, 0022-3042 KW - Cyanides KW - 0 KW - Decanoic Acids KW - Enzyme Inhibitors KW - Fluorescent Dyes KW - Hydroxy Acids KW - Neuroprotective Agents KW - Potassium Channel Blockers KW - Vasodilator Agents KW - Glutamic Acid KW - 3KX376GY7L KW - 5-hydroxydecanoic acid KW - 624-00-0 KW - Diazoxide KW - O5CB12L4FN KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Animals KW - Enzyme Inhibitors -- toxicity KW - Disease Models, Animal KW - Mice KW - Cell Hypoxia KW - Diazoxide -- pharmacology KW - Vasodilator Agents -- pharmacology KW - Neuroprotective Agents -- pharmacology KW - Hydroxy Acids -- pharmacology KW - Rats KW - Glutamic Acid -- toxicity KW - Cells, Cultured KW - Potassium Channel Blockers -- pharmacology KW - Cell Death KW - Oxidative Stress -- drug effects KW - Mice, Inbred C57BL KW - Cyanides -- toxicity KW - Male KW - Decanoic Acids -- pharmacology KW - Neurons -- metabolism KW - Brain Ischemia -- drug therapy KW - Neurons -- drug effects KW - Apoptosis -- physiology KW - Neurons -- cytology KW - Mitochondria -- metabolism KW - Brain Ischemia -- metabolism KW - Potassium -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73528293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Involvement+of+mitochondrial+K%2B+release+and+cellular+efflux+in+ischemic+and+apoptotic+neuronal+death.&rft.au=Liu%2C+Dong%3BSlevin%2C+John+R%3BLu%2C+Chengbiao%3BChan%2C+Sic+L%3BHansson%2C+Magnus%3BElm%C3%A9r%2C+Eskil%3BMattson%2C+Mark+P&rft.aulast=Liu&rft.aufirst=Dong&rft.date=2003-08-01&rft.volume=86&rft.issue=4&rft.spage=966&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 - 2003-10-01 N1 - Date created - 2003-07-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of COX inhibitors in cancer prevention and therapy. AN - 73527754; 12902856 AB - On the strength of in vitro, in vivo, observational, and clinical data, nonsteroidal antiinflammatory drugs (NSAIDs)-also referred to as COX inhibitors-have emerged as lead compounds for cancer prevention, and possible adjuncts to cancer therapy. Thus far, the routine use of NSAIDs for these indications is limited, largely owing to toxicity concerns, the paucity of efficacy data for any specific target organ, and uncertainties with regard to the most appropriate regimen (i.e., the best agent, formulation, dose, route of administration, and duration). Strategies to address these concerns primarily aim to improve the therapeutic index (i.e., benefit:risk ratio) of COX inhibitors by 1) minimizing systemic exposures whenever feasible, 2) achieving greater mechanistic specificity, 3) coadministering agents that provide prophylaxis against common toxicities, and 4) coadministering other effective anticancer agents. Clinical trials testing most of these strategies have been completed or are under way. The National Cancer Institute has a substantial research portfolio dedicated to the identification, testing, and development of NSAIDs as preventive and therapeutic anticancer agents. Discovering how to apply NSAIDs in persons with-or at risk for-cancer, although challenging, has the potential for considerable clinical and public health benefits. JF - American journal of clinical oncology AU - Umar, Asad AU - Viner, Jaye L AU - Anderson, William F AU - Hawk, Ernest T AD - Gastrointestinal & Other Cancers Research Group, National Cancer Institute, Division of Cancer Prevention, Bethesda, Maryland 20892-7317, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - S48 EP - S57 VL - 26 IS - 4 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Antineoplastic Agents KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Animals KW - Apoptosis KW - Humans KW - Research KW - Neovascularization, Pathologic KW - Risk Assessment KW - Isoenzymes -- antagonists & inhibitors KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Neoplasms -- drug therapy KW - Neoplasms -- enzymology KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology KW - Cyclooxygenase Inhibitors -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73527754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+clinical+oncology&rft.atitle=Development+of+COX+inhibitors+in+cancer+prevention+and+therapy.&rft.au=Umar%2C+Asad%3BViner%2C+Jaye+L%3BAnderson%2C+William+F%3BHawk%2C+Ernest+T&rft.aulast=Umar&rft.aufirst=Asad&rft.date=2003-08-01&rft.volume=26&rft.issue=4&rft.spage=S48&rft.isbn=&rft.btitle=&rft.title=American+journal+of+clinical+oncology&rft.issn=1537-453X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-28 N1 - Date created - 2003-08-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abatement of cockroach allergen (Bla g 1) in low-income, urban housing: A randomized controlled trial. AN - 73527114; 12897740 AB - Clinically relevant reductions in exposure to cockroach allergen, an important risk factor for asthma in inner-city households, have proven difficult to achieve in intervention trials. This study investigated a method for the abatement of cockroach allergen in low-income, urban homes. The goal was to reduce mean Bla g 1 concentrations below the previously proposed thresholds for allergic sensitization and asthma morbidity. A prerandomized, nonmasked trial with 16 intervention and 15 control homes was conducted. Study inclusion was based on 50 to 500 cockroaches trapped in a 3-day period. The interventions consisted of occupant education, placement of insecticide bait, and professional cleaning. Vacuumed dust and multiple swab samples were collected at 0, 1, 2, 4, and 6 months in intervention homes and at 0 and 6 months in control homes. Room maps containing cockroach and allergen data were used to guide and monitor the interventions. From 0 to 6 months among intervention homes, geometric mean Bla g 1 concentrations (U/g dust) decreased from 633 to 24 on kitchen floors (96% reduction), from 25 to 4.3 on living room floors/sofas (83% reduction), from 46 to 7.3 on bedroom floors (84% reduction), and from 6.1 to 1.0 in bedroom beds (84% reduction). These reductions, with the exception of that on the bedroom floor (P =.06), were statistically significant relative to changes in control homes. Substantial reductions in cockroach allergen levels can be achieved in inner-city homes. In this study, allergen levels were reduced below the sensitization threshold (2 U/g) in beds, arguably the most relevant site for exposure, and below the asthma morbidity threshold (8 U/g) on bedroom floors and living room floors/sofas. The level on kitchen floors, although reduced 96%, remained above the asthma morbidity threshold. Future studies will test the intervention's effectiveness in asthma prevention trials. JF - The Journal of allergy and clinical immunology AU - Arbes, Samuel J AU - Sever, Michelle AU - Archer, Janet AU - Long, Elizabeth H AU - Gore, J Chad AU - Schal, Coby AU - Walter, Michelle AU - Nuebler, Betsy AU - Vaughn, Ben AU - Mitchell, Herman AU - Liu, Eric AU - Collette, Nicholas AU - Adler, Peter AU - Sandel, Megan AU - Zeldin, Darryl C AD - Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 339 EP - 345 VL - 112 IS - 2 SN - 0091-6749, 0091-6749 KW - Allergens KW - 0 KW - Antigens, Plant KW - Insecticides KW - allergen Bla g 1 KW - Abridged Index Medicus KW - Index Medicus KW - Osmolar Concentration KW - Housekeeping KW - Patient Education as Topic KW - Differential Threshold KW - Humans KW - Insecticides -- pharmacology KW - Immunization KW - Insect Control KW - Allergens -- immunology KW - Housing KW - Urban Population KW - Poverty Areas KW - Allergens -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73527114?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+allergy+and+clinical+immunology&rft.atitle=Abatement+of+cockroach+allergen+%28Bla+g+1%29+in+low-income%2C+urban+housing%3A+A+randomized+controlled+trial.&rft.au=Arbes%2C+Samuel+J%3BSever%2C+Michelle%3BArcher%2C+Janet%3BLong%2C+Elizabeth+H%3BGore%2C+J+Chad%3BSchal%2C+Coby%3BWalter%2C+Michelle%3BNuebler%2C+Betsy%3BVaughn%2C+Ben%3BMitchell%2C+Herman%3BLiu%2C+Eric%3BCollette%2C+Nicholas%3BAdler%2C+Peter%3BSandel%2C+Megan%3BZeldin%2C+Darryl+C&rft.aulast=Arbes&rft.aufirst=Samuel&rft.date=2003-08-01&rft.volume=112&rft.issue=2&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+allergy+and+clinical+immunology&rft.issn=00916749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-05 N1 - Date created - 2003-08-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Allergy Clin Immunol. 2003 Aug;112(2):265-7 [12897730] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Tg.AC mouse model passes test by failing to respond. AN - 73526896; 12892072 JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Cannon, Ronald E AD - Cancer Biology Group, National Center for Toxicogenomics, NIEHS, Research Triangle Park, North Carolina 27709, USA. cannon1@niehs.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 233 EP - 234 VL - 74 IS - 2 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - Index Medicus KW - Skin Neoplasms -- genetics KW - Animals KW - Carcinogens -- administration & dosage KW - Skin Neoplasms -- chemically induced KW - Models, Genetic KW - Carcinogens -- toxicity KW - Mice KW - Administration, Topical KW - Genes, ras KW - Animal Testing Alternatives KW - Carcinogenicity Tests -- methods KW - Disease Models, Animal KW - Mice, Transgenic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73526896?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=The+Tg.AC+mouse+model+passes+test+by+failing+to+respond.&rft.au=Cannon%2C+Ronald+E&rft.aulast=Cannon&rft.aufirst=Ronald&rft.date=2003-08-01&rft.volume=74&rft.issue=2&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-17 N1 - Date created - 2003-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of cre recombinase activity using modified androgen receptor ligand binding domains: a sensitive assay for ligand-receptor interactions. AN - 73524958; 12888538 AB - Novel systems of inducible gene expression are presented in which CRE-M, an altered form of cre recombinase (cre), is fused to and activated by ligand binding to two forms of the androgen receptor (AR) ligand binding domain (LBD). Selective activation or inactivation of gene transcription is induced upon the addition of appropriate ligand. The coupling of this cre-LBD system with our previously reported highly sensitive assay to measure cre activity in vitro using a dual fluorescent gene switch reporter provides a novel, high-throughput assay system for identifying compounds that bind to and activate various forms of the LBD of androgen receptor. This method can similarly be applied to screen compounds for their activating properties on other steroid hormone LBDs. Three different forms of the AR-LBD were fused to CRE-M, including the wild-type AR-LBD (wt), a non-ligand binding truncated form, LBD (T), and a mutated form (Thr-->Ala substitution) identified in the LNCaP prostate cancer cell line, LBD (LNCaP). We demonstrate a 10-fold induction of cre activity by the addition of androgen agonists to the CRE-M-AR-LBD(wt) fusion protein, but not in the presence of the anti-androgen, flutamide. However, cre activity can be induced by flutamide with the CRE-M-AR-LBD(LNCaP) fusion protein. Similar activation properties were obtained when these fusion proteins were expressed using adenoviral vectors. When combined with our previously reported cre-lox gene switch system, the CRE-M-AR-LBD system can be utilized in gene therapy systems in which a therapeutic product may be initially expressed, replaced by a second product, or turned-off following exposure to ligand. This provides an important, additional level of regulation to gene therapy systems. JF - Nucleic acids research AU - Kaczmarczyk, Stanislaw J AU - Green, Jeffrey E AD - Transgenic Oncogenesis Group, Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2003/08/01/ PY - 2003 DA - 2003 Aug 01 SP - 1 VL - 31 IS - 15 KW - Androgen Antagonists KW - 0 KW - Androgens KW - Ligands KW - Receptors, Androgen KW - Recombinant Fusion Proteins KW - Viral Proteins KW - Cre recombinase KW - EC 2.7.7.- KW - Integrases KW - Index Medicus KW - Animals KW - Androgen Antagonists -- pharmacology KW - Androgens -- pharmacology KW - Transcriptional Activation KW - Adenoviridae -- genetics KW - Recombinant Fusion Proteins -- metabolism KW - Microscopy, Fluorescence KW - Genetic Vectors KW - Genes, Reporter KW - CHO Cells KW - Genetic Therapy -- methods KW - Protein Structure, Tertiary KW - Cell Line KW - Cricetinae KW - Viral Proteins -- genetics KW - Integrases -- metabolism KW - Genetic Techniques KW - Integrases -- genetics KW - Receptors, Androgen -- metabolism KW - Viral Proteins -- metabolism KW - Gene Expression Regulation -- drug effects KW - Receptors, Androgen -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73524958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+cre+recombinase+activity+using+modified+androgen+receptor+ligand+binding+domains%3A+a+sensitive+assay+for+ligand-receptor+interactions.&rft.au=Kaczmarczyk%2C+Stanislaw+J%3BGreen%2C+Jeffrey+E&rft.aulast=Kaczmarczyk&rft.aufirst=Stanislaw&rft.date=2003-08-01&rft.volume=31&rft.issue=15&rft.spage=e86&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 - 2003-08-20 N1 - Date created - 2003-07-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Transgenic Res. 1998 May;7(3):181-93 [10576864] Curr Opin Biotechnol. 1999 Oct;10(5):470-6 [10508631] Dev Dyn. 1999 Dec;216(4-5):385-97 [10633858] Methods Mol Biol. 2000;136:477-85 [10840735] Cancer Gene Ther. 2000 Jun;7(6):885-92 [10880019] Curr Opin Biotechnol. 2000 Oct;11(5):455-60 [11024363] Exp Cell Res. 2000 Nov 1;260(2):334-9 [11035928] J Am Soc Nephrol. 2000 Nov;11 Suppl 16:S95-S100 [11065338] Nucleic Acids Res. 2000 Dec 1;28(23):E99 [11095695] J Cell Biol. 2001 Feb 5;152(3):645-9 [11157989] Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2467-72 [11226262] Circ Res. 2001 Mar 30;88(6):587-92 [11282892] Oncogene. 2001 Jan 18;20(3):320-8 [11313961] J Biol Chem. 2001 Apr 27;276(17):13989-94 [11278564] Methods. 2001 May;24(1):71-80 [11327805] Nucleic Acids Res. 2001 May 15;29(10):E47 [11353092] Nucleic Acids Res. 2001 Jun 15;29(12):E56-6 [11410679] Nat Rev Genet. 2001 Oct;2(10):743-55 [11584291] Nat Rev Genet. 2001 Oct;2(10):780-90 [11584294] Genes Dev. 2001 Dec 15;15(24):3243-8 [11751630] Prostate. 1989;14(2):103-15 [2710689] Biochim Biophys Acta. 1990 Apr 9;1052(1):187-94 [2322591] Biochem Biophys Res Commun. 1990 Dec 14;173(2):534-40 [2260966] Biochemistry. 1992 Mar 3;31(8):2393-9 [1540595] Plant J. 1995 Apr;7(4):687-701 [7742862] Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6991-5 [7624356] Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7376-80 [7638200] Nucleic Acids Res. 1996 Apr 15;24(8):1404-11 [8628671] Nat Biotechnol. 1997 Jan;15(1):57-62 [9035107] Curr Biol. 1998 May 21;8(11):661-4 [9635194] J Steroid Biochem Mol Biol. 1998 Apr;65(1-6):169-74 [9699870] Nucleic Acids Res. 1998 Sep 1;26(17):4086-90 [9705523] Biochem Soc Trans. 1999 Feb;27(2):78-83 [10093711] Methods Mol Biol. 1999;97:101-22 [10443361] Oncogene. 1999 Oct 28;18(44):6078-82 [10557097] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupations with increased risk of pancreatic cancer in the Swedish population. AN - 73524827; 12883017 AB - To identify occupations with increased risk of pancreatic cancer in the Swedish population gainfully employed in 1970 over the period 1971-89. The base population was made up of Swedish men (1 779 646) and Swedish women (1 101 669) gainfully employed at the time of the 1970 census and were still alive and over age 24 on 1 January 1971. Information was drawn from two data sets: the Swedish cancer environment register and a background population register. After 19 years of follow up, 4420 men and 2143 women were diagnosed with histologically confirmed incident pancreatic adenocarcinoma. Log linear Poisson models were fitted, allowing for geographical area and town size. Risk estimators were also calculated for workers reporting the same occupation in 1960 and 1970. Among women, a statistically significant risk excess of pancreatic cancer was observed for "educational methods advisors", "librarian, archivist, curator", "motor vehicle driver", "typographer, lithographer", "purser, steward, stewardess", "other housekeeping and related workers", and the groups of occupations of "electrical, electronic, and related" and "glass, pottery, and tile workers". Men showed a higher incidence of pancreatic cancer among "technical assistants", "travelling agents", "other metal processing workers", "baker and pastry cook", "docker and freight handler", and "waiters". This study does not indicate that occupational factors play an important role in the aetiology of pancreatic cancer in Sweden. Few occupations were at increased risk of pancreatic cancer in both men and women, and the associations observed are in accordance with some previous studies from Western countries. JF - Occupational and environmental medicine AU - Alguacil, J AU - Pollán, M AU - Gustavsson, P AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 570 EP - 576 VL - 60 IS - 8 SN - 1351-0711, 1351-0711 KW - Index Medicus KW - Risk Factors KW - Humans KW - Cohort Studies KW - Adult KW - Sweden -- epidemiology KW - Middle Aged KW - Poisson Distribution KW - Male KW - Female KW - Occupational Diseases -- etiology KW - Pancreatic Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology KW - Occupations KW - Pancreatic Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73524827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Occupations+with+increased+risk+of+pancreatic+cancer+in+the+Swedish+population.&rft.au=Alguacil%2C+J%3BPoll%C3%A1n%2C+M%3BGustavsson%2C+P&rft.aulast=Alguacil&rft.aufirst=J&rft.date=2003-08-01&rft.volume=60&rft.issue=8&rft.spage=570&rft.isbn=&rft.btitle=&rft.title=Occupational+and+environmental+medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-22 N1 - Date created - 2003-07-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Natl Cancer Inst. 1986 Jun;76(6):1047-51 [3458942] Carcinogenesis. 1997 May;18(5):1085-92 [9163700] Scand J Work Environ Health. 1987;13 Suppl 1:1-91 [3659854] Br J Ind Med. 1987 Nov;44(11):769-76 [3689708] J Occup Med. 1988 Sep;30(9):706-14 [3183787] Am J Ind Med. 1989;15(6):699-717 [2665480] Br J Ind Med. 1989 Nov;46(11):809-14 [2590647] Int J Cancer. 1990 Mar 15;45(3):393-6 [2407667] J Occup Environ Med. 1999 Dec;41(12):1134-9 [10609235] Occup Environ Med. 2000 May;57(5):316-24 [10769297] Ann Occup Hyg. 2000 Aug;44(5):391-403 [10930502] Int J Epidemiol. 2000 Dec;29(6):1004-13 [11101541] Am J Ind Med. 2001 Jan;39(1):92-9 [11148019] J Occup Environ Med. 2001 Mar;43(3):250-8 [11285873] Int J Cancer. 1997 Nov 27;73(5):625-8 [9398036] Med Tr Prom Ekol. 1998;(1):8-12 [9532924] Scand J Work Environ Health. 1998 Jun;24(3):165-74 [9710368] Am J Ind Med. 1999 Jan;35(1):76-81 [9884748] Int J Cancer. 1999 Mar 15;80(6):827-41 [10074914] Am J Ind Med. 1999 Aug;36(2):260-70 [10398934] Br J Cancer. 1999 Aug;80(11):1830-7 [10468306] Mayo Clin Proc. 1979 Apr;54(4):245-9 [423604] Int J Epidemiol. 1982 Dec;11(4):345-55 [7152787] J Occup Med. 1983 Jul;25(7):549-57 [6886861] Am J Ind Med. 1985;7(3):253-66 [3985017] Am J Ind Med. 1985;8(1):57-66 [4025339] Am J Epidemiol. 2001 May 1;153(9):841-50 [11323314] Chem Biol Interact. 2001 Jun 1;135-136:487-503 [11397408] Occup Environ Med. 2001 Aug;58(8):523-7 [11452047] JAMA. 2001 Aug 22-29;286(8):921-9 [11509056] J Occup Med. 1967 Jun;9(6):277-85 [6026374] J Occup Med. 1977 Aug;19(8):543-50 [894377] J Natl Cancer Inst. 1977 Oct;59(4):1147-85 [903993] Br J Ind Med. 1990 Jun;47(6):425-8 [2378821] Br J Ind Med. 1991 Sep;48(9):583-7 [1911399] FASEB J. 1992 Feb 1;6(3):853-60 [1740235] Am J Ind Med. 1991;20(6):769-74 [1805614] Int Arch Occup Environ Health. 1992;64(1):39-42 [1399013] Am J Ind Med. 1992;22(4):573-90 [1442790] J Natl Cancer Inst. 1993 Feb 17;85(4):328-9 [8426376] Int J Epidemiol. 1993 Feb;22(1):30-7 [8449644] Int J Cancer. 1994 Jun 15;57(6):786-92 [8206673] Am J Ind Med. 1994 Jun;25(6):851-66 [8067362] Cancer Causes Control. 1994 Sep;5(5):449-57 [7999967] Lakartidningen. 1995 Mar 29;92(13):1344, 1347 [7707779] Eur J Cancer Prev. 1995 Feb;4(1):81-90 [7728101] J Clin Epidemiol. 1994 Sep;47(9):1069-79 [7730910] Epidemiology. 1995 Sep;6(5):498-502 [8562625] J Epidemiol Community Health. 1995 Dec;49 Suppl 2:S15-9 [8594127] J Clin Epidemiol. 1996 May;49(5):601-3 [8636736] Occup Environ Med. 1996 Jun;53(6):394-8 [8758034] Int J Epidemiol. 1987 Jun;16(2):257-64 [3610453] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic findings and functional studies of human CYP3A5 single nucleotide polymorphisms in different ethnic groups. AN - 73523713; 12893984 AB - Genetic polymorphisms of cytochromes P450 (CYPs) are a principal reason for inter-individual variations in the metabolism of therapeutic drugs and environmental chemicals in humans. The present study identifies 34 single nucleotide polymorphisms (SNPs) of CYP3A5 including 27 previously unidentified SNPs by direct sequencing of the exons, intron-exon junctions and 5'-upstream region of CYP3A5 from 92 racially diverse individuals (24 Caucasians, 24 Africans, 24 Asians, and 20 individuals of unknown racial origin). Four new CYP3A5 SNPs produced coding changes: R28C, L82R, A337T, and F446S. CYP3A5 R28C occurred in African populations (allelic frequency of 4%). CYP3A5 A337T occurred in Asians (2% allelic frequency), CYP3A5 L82R (occurred in the racially unidentified group) and CYP3A5 F446S (identified in Caucasians with a 2% allelic frequency) were on an allele containing the splice change g.6986A>G known as CYP3A5*3. The newly identified allelic proteins were constructed by site-directed mutagenesis, expressed in Escherichia coli and purified. CYP3A5 L82R was expressed only as denatured CYP420, suggesting it may be unstable. CYP3A5*1 exhibited the highest maximal clearance for testosterone followed by CYP3A5 A337T > CYP3A5 R28C >> CYP3A5 F446S. CYP3A5*1 exhibited a higher V(max) for nifedipine oxidation than CYP3A5 A337T > CYP3A5 R28C >> CYP3A5 F446S. CYP3A5 A337T and CYP3A5 R28C exhibited a 42-64% lower V(max) for nifedipine oxidation than CYP3A5*1. CYP3A5 F446S exhibited a > 95% decrease in the intrinsic clearance for both 6beta-hydroxytestosterone and nifedipine oxidation. This study identifies four new potentially defective coding alleles. CYP3A5 F446S is predicted to be more catalytically defective than the splice change alone. JF - Pharmacogenetics AU - Lee, Su-Jun AU - Usmani, Khawja A AU - Chanas, Brian AU - Ghanayem, Burhan AU - Xi, Tina AU - Hodgson, Ernest AU - Mohrenweiser, Harvey W AU - Goldstein, Joyce A AD - Human Metabolism Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 461 EP - 472 VL - 13 IS - 8 SN - 0960-314X, 0960-314X KW - DNA Primers KW - 0 KW - DNA, Complementary KW - Testosterone KW - 3XMK78S47O KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - CYP3A protein, human KW - EC 1.14.14.1 KW - CYP3A5 protein, human KW - Cytochrome P-450 CYP3A KW - Nifedipine KW - I9ZF7L6G2L KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Alleles KW - Nifedipine -- pharmacokinetics KW - Humans KW - Escherichia coli -- genetics KW - Testosterone -- pharmacokinetics KW - Polymorphism, Single Nucleotide KW - Cytochrome P-450 Enzyme System -- genetics KW - Ethnic Groups -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73523713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=Genetic+findings+and+functional+studies+of+human+CYP3A5+single+nucleotide+polymorphisms+in+different+ethnic+groups.&rft.au=Lee%2C+Su-Jun%3BUsmani%2C+Khawja+A%3BChanas%2C+Brian%3BGhanayem%2C+Burhan%3BXi%2C+Tina%3BHodgson%2C+Ernest%3BMohrenweiser%2C+Harvey+W%3BGoldstein%2C+Joyce+A&rft.aulast=Lee&rft.aufirst=Su-Jun&rft.date=2003-08-01&rft.volume=13&rft.issue=8&rft.spage=461&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-22 N1 - Date created - 2003-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Production and purification of refolded recombinant human IL-7 from inclusion bodies. AN - 73520631; 12880763 AB - A recombinant form of human rhIL-7 was overexpressed in Escherichia coli HMS174 (DE3) pLysS under the control of a T7 promoter. The resulting insoluble inclusion bodies were separated from cellular debris by cross-flow filtration and solubilized by homogenization with 6 M guanidine HCl. Attempts at refolding rhIL-7 from solubilized inclusion bodies without prior purification of monomeric, denatured rhIL-7 were not successful. Denatured, monomeric rhIL-7 was therefore initially purified by size-exclusion chromatography using Prep-Grade Pharmacia Superdex 200. Correctly folded rhIL-7 monomer was generated by statically refolding the denatured protein at a final protein concentration of 80-100 microg/ml in 100 mM Tris, 2mM EDTA, 500 mM L-arginine, pH 9.0, buffer with 0.55 g/l oxidized glutathione at 2-8 degrees C for at least 48 h. The refolded rhIL-7 was subsequently purified by low-pressure liquid chromatography, using a combination of hydrophobic interaction, cation-exchange, and size-exclusion chromatography. The purified final product was >95% pure by SDS-PAGE stained with Coomassie brilliant blue, high-pressure size-exclusion chromatography (SEC-HPLC), and reverse-phase HPLC. The endotoxin level was <0.05 EU/mg. The final purified product was biologically active in a validated IL-7 dependent pre-B-cell bioassay. In anticipation of human clinical trials, this material is currently being evaluated for safety and efficacy in non-human primate toxicology studies. JF - Protein expression and purification AU - Ouellette, Thomas AU - Destrau, Sophie AU - Ouellette, Timothy AU - Zhu, Jianwei AU - Roach, John M AU - Coffman, J Daniel AU - Hecht, Toby AU - Lynch, James E AU - Giardina, Steven L AD - Biopharmaceutical Development Program, National Cancer Institute at Frederick, SAIC-Frederick, Inc., Frederick, MD 21702-1201, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 156 EP - 166 VL - 30 IS - 2 SN - 1046-5928, 1046-5928 KW - Interleukin-7 KW - 0 KW - Recombinant Proteins KW - Index Medicus KW - Recombinant Proteins -- isolation & purification KW - Recombinant Proteins -- pharmacology KW - Recombinant Proteins -- biosynthesis KW - Fermentation KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Protein Denaturation KW - Escherichia coli KW - Recombinant Proteins -- chemistry KW - Quality Control KW - Protein Renaturation KW - Interleukin-7 -- chemistry KW - Interleukin-7 -- genetics KW - Protein Folding KW - Inclusion Bodies -- chemistry KW - Interleukin-7 -- pharmacology KW - Interleukin-7 -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73520631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+expression+and+purification&rft.atitle=Production+and+purification+of+refolded+recombinant+human+IL-7+from+inclusion+bodies.&rft.au=Ouellette%2C+Thomas%3BDestrau%2C+Sophie%3BOuellette%2C+Timothy%3BZhu%2C+Jianwei%3BRoach%2C+John+M%3BCoffman%2C+J+Daniel%3BHecht%2C+Toby%3BLynch%2C+James+E%3BGiardina%2C+Steven+L&rft.aulast=Ouellette&rft.aufirst=Thomas&rft.date=2003-08-01&rft.volume=30&rft.issue=2&rft.spage=156&rft.isbn=&rft.btitle=&rft.title=Protein+expression+and+purification&rft.issn=10465928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-01 N1 - Date created - 2003-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol consumption in relation to risk of cholecystectomy in women. AN - 73519274; 12885719 AB - Alcohol consumption has been linked to a lower risk of gallstone disease. However, the magnitude of the association is uncertain, and little is known about the relation of alcohol consumption patterns and individual types of alcoholic beverages to gallstone disease risk. We prospectively examined the association between alcohol intake and cholecystectomy, a surrogate for symptomatic gallstone disease, in a large cohort of women. Women from the Nurses' Health Study who had no history of gallstone disease in 1980 (n = 80,898) were followed for 20 y. Alcohol consumption, which was measured every 2-4 y by food-frequency questionnaires, was used to predict subsequent cholecystectomy through multivariate analysis. We ascertained 7831 cases of cholecystectomy. Relative to subjects who had no alcohol intake, subjects who had alcohol intakes of 0.1-4.9, 5.0-14.9, 15.0-29.9, 30.0-49.9, and >/=50.0 g/d had multivariate relative risks of cholecystectomy of 0.95, 0.86, 0.80, 0.67, and 0.62 (95% CI: 0.49, 0.79), respectively. Relative to subjects who never consumed alcohol, subjects who consumed alcohol 1-2, 3-4, 5-6, and 7 d/wk had multivariate relative risks of cholecystectomy of 0.94, 0.88, 0.87, and 0.73 (0.63, 0.84), respectively. All alcoholic beverage types were inversely associated with cholecystectomy risk, independent of consumption patterns (for quantity of alcohol consumed, P = 0.04, 0.001, and 0.003 for wine, beer, and liquor, respectively; for frequency of alcohol consumption, P = 0.01, 0.07, and <0.0001 for wine, beer, and liquor, respectively). The intake of all alcoholic beverage types is inversely associated with the risk of cholecystectomy. Recommendations regarding the benefit of consuming moderate quantities of alcohol should be weighed against the potential health hazards. JF - The American journal of clinical nutrition AU - Leitzmann, Michael F AU - Tsai, Chung-Jyi AU - Stampfer, Meir J AU - Rimm, Eric B AU - Colditz, Graham A AU - Willett, Walter C AU - Giovannucci, Edward L AD - Department of Nutrition, Harvard School of Public Health, Boston, USA. leitzmann@mail.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 339 EP - 347 VL - 78 IS - 2 SN - 0002-9165, 0002-9165 KW - Abridged Index Medicus KW - Index Medicus KW - Risk KW - Prospective Studies KW - Humans KW - Health Status KW - Adult KW - Surveys and Questionnaires KW - Middle Aged KW - Female KW - Gallbladder Diseases -- prevention & control KW - Cholecystectomy KW - Alcohol Drinking KW - Gallbladder Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73519274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+clinical+nutrition&rft.atitle=Alcohol+consumption+in+relation+to+risk+of+cholecystectomy+in+women.&rft.au=Leitzmann%2C+Michael+F%3BTsai%2C+Chung-Jyi%3BStampfer%2C+Meir+J%3BRimm%2C+Eric+B%3BColditz%2C+Graham+A%3BWillett%2C+Walter+C%3BGiovannucci%2C+Edward+L&rft.aulast=Leitzmann&rft.aufirst=Michael&rft.date=2003-08-01&rft.volume=78&rft.issue=2&rft.spage=339&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+clinical+nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-19 N1 - Date created - 2003-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selected as the best paper in JAGS in the 1970s mission of the National Institute on Aging. AN - 73517658; 12890084 AB - The National Institute on Aging (NIA), the newest of the 11 National Institutes of Health, is dedicated to improving the quality of life of the old in America through biomedical, social, and behavioral research. Aging is viewed as more than just decline and deterioration; it is also a process of continued development and accumulated knowledge. The NIA will encourage innovative research but will not support the delivery of health services, as that is the domain of the other agencies. In areas of overlap, such as diseases common to the old, the NIA will collaborate with other Institutes. A good target area for collaboration is senile dementia. Other areas of interest to the NIA are: encouraging the incorporation of geriatric medicine as a subspecialty, developing retirement test patterns, and investigating drug-drug and drug-age interactions, personality and social processes, and immunocompetence. JF - Journal of the American Geriatrics Society AU - Butler, Robert N AD - National Institute on Aging, Bethesda, Maryland 20014, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 1169 EP - 1173 VL - 51 IS - 8 SN - 0002-8614, 0002-8614 KW - Index Medicus KW - United States KW - Education, Medical KW - Drug Interactions KW - Geriatrics -- education KW - Humans KW - Aged KW - Organizational Objectives KW - Research KW - Retirement KW - National Institutes of Health (U.S.) -- organization & administration KW - Aging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73517658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Geriatrics+Society&rft.atitle=Selected+as+the+best+paper+in+JAGS+in+the+1970s+mission+of+the+National+Institute+on+Aging.&rft.au=Butler%2C+Robert+N&rft.aulast=Butler&rft.aufirst=Robert&rft.date=2003-08-01&rft.volume=51&rft.issue=8&rft.spage=1169&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Geriatrics+Society&rft.issn=00028614&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-02 N1 - Date created - 2003-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calcium dependence of the interaction between calmodulin and anthrax edema factor. AN - 73512054; 12724328 AB - Edema factor (EF), a toxin from Bacillus anthracis (anthrax), possesses adenylyl cyclase activity and requires the ubiquitous Ca2+-sensor calmodulin (CaM) for activity. CaM can exist in three major structural states: an apo state with no Ca2+ bound, a two Ca2+ state with its C-terminal domain Ca2+-loaded, and a four Ca2+ state in which the lower Ca2+ affinity N-terminal domain is also ligated. Here, the interaction of EF with the three Ca2+ states of CaM has been examined by NMR spectroscopy and changes in the Ca2+ affinity of CaM in the presence of EF have been determined by flow dialysis. Backbone chemical shift perturbations of CaM show that EF interacts weakly with the N-terminal domain of apoCaM. The C-terminal CaM domain only engages in the interaction upon Ca2+ ligation, rendering the overall interaction much tighter. In the presence of EF, the C-terminal domain binds Ca2+ with higher affinity, but loses binding cooperativity, whereas the N-terminal domain exhibits strongly reduced Ca2+ affinity. As judged by chemical shift differences, the N-terminal CaM domain remains bound to EF upon subsequent Ca2+ ligation. This Ca2+ dependence of the EF-CaM interaction differs from that observed for most other CaM targets, which normally interact only with the Ca2+-bound CaM domains and become active following the transition to the four Ca2+ state. JF - The Journal of biological chemistry AU - Ulmer, Tobias S AU - Soelaiman, Sandriyana AU - Li, Shipeng AU - Klee, Claude B AU - Tang, Wei-Jen AU - Bax, Ad AD - Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/08/01/ PY - 2003 DA - 2003 Aug 01 SP - 29261 EP - 29266 VL - 278 IS - 31 SN - 0021-9258, 0021-9258 KW - Antigens, Bacterial KW - 0 KW - Apoproteins KW - Bacterial Toxins KW - Calmodulin KW - Peptide Fragments KW - anthrax toxin KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Molecular Structure KW - Drug Interactions KW - Bacillus anthracis -- chemistry KW - Apoproteins -- chemistry KW - Models, Molecular KW - Apoproteins -- metabolism KW - Magnetic Resonance Spectroscopy KW - Calmodulin -- metabolism KW - Calcium -- metabolism KW - Calmodulin -- chemistry KW - Adenylyl Cyclases -- metabolism KW - Calcium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73512054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Calcium+dependence+of+the+interaction+between+calmodulin+and+anthrax+edema+factor.&rft.au=Ulmer%2C+Tobias+S%3BSoelaiman%2C+Sandriyana%3BLi%2C+Shipeng%3BKlee%2C+Claude+B%3BTang%2C+Wei-Jen%3BBax%2C+Ad&rft.aulast=Ulmer&rft.aufirst=Tobias&rft.date=2003-08-01&rft.volume=278&rft.issue=31&rft.spage=29261&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 - 2003-09-10 N1 - Date created - 2003-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple primary tumors involving cancer of the brain and central nervous system as the first or subsequent cancer. AN - 73508726; 12879474 AB - This study was undertaken to determine whether cancer of the brain and central nervous system (CNS) occurs together with other types of cancer more often or less often than would be expected due to chance. The study was based on data collected by the Surveillance, Epidemiology, and End Results (SEER) Program for cancers diagnosed in the U.S. between 1973 and 1998. The standardized incidence ratio (SIR) for new malignancies was estimated as the number of patients diagnosed with a particular type of cancer (observed), divided by the number of diagnoses expected based on person-years of follow-up and incidence rates for SEER cancer registries. Among patients who were diagnosed first with cancer of the brain or CNS, statistically significant excesses were observed for cancers of bone (SIR = 14.4), soft tissue (SIR = 4.6), brain and CNS (SIR = 5.9), salivary gland (SIR = 5.1), and thyroid gland (SIR = 2.7) in addition to acute myelocytic leukemia (SIR = 4.1) and melanoma of the skin (SIR = 1.7). Excess risk of new malignancies was markedly greater after first cancers of the brain or CNS diagnosed in childhood compared with similar diagnoses in adulthood. In reverse associations, significant excesses of cancer of the brain and CNS were observed only after diagnoses of acute lymphocytic leukemia (SIR = 7.4) and cancer of the testis (SIR = 1.8) or the thyroid gland (SIR = 1.7). Cancer treatment appears to have been the major factor underlying most of the positive associations between brain cancer and primary cancers of other types, with a probable lesser contribution from shared genetic susceptibility. Results provide little or no evidence that brain cancer shares important etiologic factors with the common cancers of adulthood. JF - Cancer AU - Inskip, Peter D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA. inskippe@mail.nih.gov Y1 - 2003/08/01/ PY - 2003 DA - 2003 Aug 01 SP - 562 EP - 570 VL - 98 IS - 3 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Brain Neoplasms -- pathology KW - Brain Neoplasms -- therapy KW - Brain Neoplasms -- epidemiology KW - Humans KW - SEER Program KW - Incidence KW - Middle Aged KW - Follow-Up Studies KW - United States -- epidemiology KW - Male KW - Female KW - Radiotherapy -- adverse effects KW - Antineoplastic Agents -- adverse effects KW - Neoplasms, Multiple Primary -- therapy KW - Neoplasms, Second Primary -- therapy KW - Central Nervous System Neoplasms -- therapy KW - Central Nervous System Neoplasms -- pathology KW - Neoplasms, Second Primary -- epidemiology KW - Neoplasms, Multiple Primary -- pathology KW - Neoplasms, Multiple Primary -- epidemiology KW - Central Nervous System Neoplasms -- epidemiology KW - Neoplasms, Second Primary -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73508726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Multiple+primary+tumors+involving+cancer+of+the+brain+and+central+nervous+system+as+the+first+or+subsequent+cancer.&rft.au=Inskip%2C+Peter+D&rft.aulast=Inskip&rft.aufirst=Peter&rft.date=2003-08-01&rft.volume=98&rft.issue=3&rft.spage=562&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-14 N1 - Date created - 2003-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted introduction of a diphtheria toxin resistant mutation into the chromosomal EF-2 locus of Pichia pastoris and expression of immunotoxin in the EF-2 mutants. AN - 73508491; 12880776 AB - In an attempt to increase the production of a diphtheria toxin (DT) based immunotoxin by Pichia pastoris, we have created DT-resistant mutants that contain a substitution of arginine for glycine at position 701 in elongation factor 2 (EF-2). To achieve this, we first cloned and characterized the EF-2 gene (PEF1), and then made a construct pBLURA-Delta5'mutEF-2 that efficiently introduces specific mutations into the chromosomal EF-2 gene in P. pastoris by in vivo homologous recombination. pBLURA-Delta5(')mutEF-2 contains a selection marker URA3 and a 5' truncated form of the P. pastoris PEF1 that had been modified in vitro to carry the nucleotide mutations for the Gly(701) to Arg transition. Unlike the non-mutated strains, the EF-2 mutants are resistant to high-level intracellular expression of DT A chain that can catalyze the ADP-ribosylation. When used to express the secreted bivalent anti-T cell immunotoxin, A-dmDT390-bisFv(G4S), the EF-2 mutant strains showed increased viability compared to the non-mutated strains. However, they did not show an advantage over the non-mutated expressing strain in the production of the immunotoxin. Western blotting analysis revealed that although the EF-2 mutants did not increase the accumulation of intact A-dmDT390-bisFv(G4S) in the culture medium, they generated larger amounts of degraded products found in both the medium and cell pellets compared to the non-mutant expressing clone. In addition, double copy expression resulted in greater amounts of intact immunotoxin being retained within cellular compartments as well as degraded products. Based on these findings, we suggest that the secretory capacity may be rate limiting for divalent immunotoxin production in P. pastoris. JF - Protein expression and purification AU - Liu, Yuan Yi AU - Woo, Jung Hee AU - Neville, David M AD - National Institute of Mental Health, NIH, Bethesda, MD 28092-4034, USA. yyliu@codon.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 262 EP - 274 VL - 30 IS - 2 SN - 1046-5928, 1046-5928 KW - Culture Media KW - 0 KW - Diphtheria Toxin KW - Immunotoxins KW - Peptide Elongation Factor 2 KW - Index Medicus KW - Base Sequence KW - Recombination, Genetic -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Culture Media -- chemistry KW - Cloning, Molecular KW - Diphtheria Toxin -- chemistry KW - Pichia -- genetics KW - Peptide Elongation Factor 2 -- genetics KW - Pichia -- metabolism KW - Immunotoxins -- metabolism KW - Diphtheria Toxin -- genetics KW - Drug Resistance, Fungal -- genetics KW - Immunotoxins -- chemistry KW - Diphtheria Toxin -- biosynthesis KW - Diphtheria Toxin -- pharmacology KW - Mutation -- genetics KW - Immunotoxins -- genetics KW - Immunotoxins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73508491?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+expression+and+purification&rft.atitle=Targeted+introduction+of+a+diphtheria+toxin+resistant+mutation+into+the+chromosomal+EF-2+locus+of+Pichia+pastoris+and+expression+of+immunotoxin+in+the+EF-2+mutants.&rft.au=Liu%2C+Yuan+Yi%3BWoo%2C+Jung+Hee%3BNeville%2C+David+M&rft.aulast=Liu&rft.aufirst=Yuan&rft.date=2003-08-01&rft.volume=30&rft.issue=2&rft.spage=262&rft.isbn=&rft.btitle=&rft.title=Protein+expression+and+purification&rft.issn=10465928&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-01 N1 - Date created - 2003-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeting membrane-localized focal adhesion kinase to focal adhesions: roles of tyrosine phosphorylation and SRC family kinases. AN - 73503575; 12754219 AB - In the present study, we examined regulation of activated focal adhesion kinase localization in focal adhesions. By using focal adhesion kinase fused to an inert transmembrane anchor, we found that the focal contact targeting region within focal adhesion kinase was preserved in the membrane-targeted fusion protein. However, upon tyrosine phosphorylation, full-length focal adhesion kinase became excluded from focal adhesions. This negative regulation of localization could be abolished by mutating key amino acid residues of focal adhesion kinase shown previously to be involved in adhesion-mediated signal transduction. Hyper-phosphorylation of endogenous focal adhesion kinase induced by pervanadate resulted in a similar reduction of localization at focal adhesions. We also show here that Src family kinases are essential for the phosphorylation-dependent exclusion of focal adhesion kinase from focal adhesions. We propose here a molecular model for the tyrosine phosphorylation-dependent regulation of focal adhesion kinase organization involving Src kinases and an inhibitory phosphorylation of the C-terminal (Tyr-925) tyrosine residue. JF - The Journal of biological chemistry AU - Katz, Ben-Zion AU - Romer, Lewis AU - Miyamoto, Shingo AU - Volberg, Tova AU - Matsumoto, Kazue AU - Cukierman, Edna AU - Geiger, Benjamin AU - Yamada, Kenneth M AD - Craniofacial Developmental Biology and Regeneration Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/08/01/ PY - 2003 DA - 2003 Aug 01 SP - 29115 EP - 29120 VL - 278 IS - 31 SN - 0021-9258, 0021-9258 KW - Receptors, Interleukin-2 KW - 0 KW - Recombinant Fusion Proteins KW - Vinculin KW - 125361-02-6 KW - Tyrosine KW - 42HK56048U KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Focal Adhesion Kinase 1 KW - EC 2.7.10.2 KW - Focal Adhesion Protein-Tyrosine Kinases KW - PTK2 protein, human KW - Ptk2 protein, mouse KW - src-Family Kinases KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Cell Membrane -- enzymology KW - src-Family Kinases -- deficiency KW - Fluorescent Antibody Technique, Indirect KW - Humans KW - Gene Expression KW - Mice KW - Receptors, Interleukin-2 -- genetics KW - Fibroblasts -- metabolism KW - Mutagenesis KW - Polymerase Chain Reaction KW - Phosphorylation KW - Transfection KW - src-Family Kinases -- metabolism KW - Tyrosine -- metabolism KW - Vinculin -- genetics KW - Protein-Tyrosine Kinases -- genetics KW - Focal Adhesions -- enzymology KW - Protein-Tyrosine Kinases -- metabolism KW - Protein-Tyrosine Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73503575?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Targeting+membrane-localized+focal+adhesion+kinase+to+focal+adhesions%3A+roles+of+tyrosine+phosphorylation+and+SRC+family+kinases.&rft.au=Katz%2C+Ben-Zion%3BRomer%2C+Lewis%3BMiyamoto%2C+Shingo%3BVolberg%2C+Tova%3BMatsumoto%2C+Kazue%3BCukierman%2C+Edna%3BGeiger%2C+Benjamin%3BYamada%2C+Kenneth+M&rft.aulast=Katz&rft.aufirst=Ben-Zion&rft.date=2003-08-01&rft.volume=278&rft.issue=31&rft.spage=29115&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 - 2003-09-10 N1 - Date created - 2003-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Animal production and wheeze in the Agricultural Health Study: interactions with atopy, asthma, and smoking. AN - 73499432; 12883030 AB - Exposure to animals, their feeds, and by-products contribute to respiratory symptoms among farmers. To investigate the role of animal exposures and wheeze, and to assess whether their impact differs among susceptible subgroups, including atopics, asthmatics, and smokers. Using the Agricultural Health Study, a cohort of pesticide applicators in Iowa and North Carolina enrolled in 1994-97, wheeze associated with animal production was evaluated and interactions among susceptible subgroups assessed. Logistic regression models were used to examine risk factors for wheeze in the past year among 20 468 farmers. Individuals raising animals requiring direct contact had the highest odds ratios (OR) for wheeze (OR(dairy) = 1.26; OR(eggs) = 1.70). A significant dose response was observed for both the number of poultry and the number of livestock on the farm. Farmers who performed veterinary procedures on a daily basis had an OR of 1.51. The odds of wheeze associated with poultry production was greater among atopic than non-atopic individuals. Milking cows daily increased the odds of wheeze in all individuals, with the largest association observed among atopic asthmatic individuals. The impact of dairy, poultry, and egg production varied among smoking groups. Past smokers had the highest odds ratios, followed by never smokers, and then current smokers. The OR(eggs) was 2.88 among past smokers but only 1.46 for never smokers. The OR(eggs) for current smokers of 0.80 might reflect self selection of exposure among smokers. Results are consistent with animal production and respiratory symptoms, and suggest that subgroups may respond differently to exposure. JF - Occupational and environmental medicine AU - Hoppin, J A AU - Umbach, D M AU - London, S J AU - Alavanja, M C R AU - Sandler, D P AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709-2233, USA. hoppin1@niehs.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 1 VL - 60 IS - 8 SN - 1351-0711, 1351-0711 KW - Index Medicus KW - Animals KW - Asthma -- etiology KW - Humans KW - Smoking -- adverse effects KW - Aged KW - Cross-Sectional Studies KW - Aged, 80 and over KW - Logistic Models KW - Risk Factors KW - Adult KW - Middle Aged KW - Adolescent KW - Female KW - Iowa -- epidemiology KW - Male KW - Respiratory Sounds KW - Respiratory Hypersensitivity -- etiology KW - Agricultural Workers' Diseases -- etiology KW - Animal Husbandry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73499432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+environmental+medicine&rft.atitle=Animal+production+and+wheeze+in+the+Agricultural+Health+Study%3A+interactions+with+atopy%2C+asthma%2C+and+smoking.&rft.au=Hoppin%2C+J+A%3BUmbach%2C+D+M%3BLondon%2C+S+J%3BAlavanja%2C+M+C+R%3BSandler%2C+D+P&rft.aulast=Hoppin&rft.aufirst=J&rft.date=2003-08-01&rft.volume=60&rft.issue=8&rft.spage=e3&rft.isbn=&rft.btitle=&rft.title=Occupational+and+environmental+medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-22 N1 - Date created - 2003-07-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Allergy Clin Immunol. 1984 Jan;73(1 Pt 1):56-60 [6693668] J Allergy Clin Immunol. 1983 Sep;72(3):299-304 [6886262] Thorax. 1986 Feb;41(2):117-21 [3704977] J Occup Med. 1987 Jan;29(1):38-43 [3819883] Eur J Respir Dis Suppl. 1987;152:206-11 [3499343] Clin Allergy. 1987 Sep;17(5):417-23 [3499998] Int Arch Allergy Appl Immunol. 1988;87(2):171-7 [3192304] Thorax. 1988 Nov;43(11):872-7 [3222758] Eur Respir J. 1989 Nov;2(10):940-5 [2606194] Am J Ind Med. 1990;17(1):7-15 [2407117] Am J Ind Med. 1990;17(1):73-4 [2305796] Am J Ind Med. 1990;17(1):77-8 [2305798] Med J Aust. 1990 May 21;152(10):521-4 [2338925] Respiration. 1990;57(3):137-44 [2274712] Am J Ind Med. 1991;19(2):195-204 [1992677] Chest. 1991 Apr;99(4):941-4 [2009799] Br J Ind Med. 1991 May;48(5):323-6 [2039744] Occup Med. 1991 Jul-Sep;6(3):415-28 [1948527] Chest. 1993 Feb;103(2):417-21 [8432130] Am J Ind Med. 1993 Dec;24(6):713-22 [8311102] Scand J Work Environ Health. 1994 Feb;20(1):48-54 [8016599] Occup Environ Med. 1995 Oct;52(10):654-60 [7489055] Environ Res. 1995 Jul;70(1):11-9 [8603653] Environ Health Perspect. 1996 Apr;104(4):362-9 [8732939] Int J Epidemiol. 1996 Jun;25(3):609-16 [8671563] Am J Ind Med. 1996 Feb;29(2):201-7 [8821364] Eur Respir J. 1996 Jul;9(7):1407-13 [8836651] Am J Ind Med. 1997 Feb;31(2):233-42 [9028440] Occup Environ Med. 1997 May;54(5):301-6 [9196450] Scand J Work Environ Health. 1997 Aug;23(4):271-80 [9322818] Scand J Work Environ Health. 1998 Aug;24(4):262-9 [9754857] Occup Environ Med. 1998 May;55(5):349-55 [9764113] J Toxicol Clin Toxicol. 1998;36(6):557-65 [9776958] Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1493-8 [9817698] Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 2):S1-S76 [9817727] Am J Ind Med. 1999 Jan;35(1):51-7 [9884745] Am J Ind Med. 1999 Feb;35(2):150-63 [9894539] Int J Tuberc Lung Dis. 1999 Mar;3(3):185-91 [10094317] Thorax. 1999 Mar;54(3):268-72 [10325905] Occup Med. 1999 Apr-Jun;14(2):337-50 [10329909] Am J Ind Med. 1999 Oct;36(4):444-9 [10470009] Am J Ind Med. 2000 May;37(5):451-8 [10723039] J Occup Environ Med. 2000 Mar;42(3):260-9 [10738705] Thorax. 2000 May;55(5):424-31 [10770825] Eur Respir J. 1999 Jan;13(1):187-9 [10836346] Arch Intern Med. 2000 Jun 12;160(11):1683-9 [10847262] J Occup Environ Med. 2000 Aug;42(8):814-20 [10953819] Ann Agric Environ Med. 2000;7(2):71-8 [11153034] Eur Respir J. 2000 Nov;16(5):886-92 [11153588] Am J Ind Med. 2001 Mar;39(3):292-300 [11241562] Am J Ind Med. 2001 Apr;39(4):410-8 [11323791] Occup Environ Med. 2001 Jun;58(6):405-10 [11351057] Eur Respir J. 2001 Apr;17(4):747-54 [11401073] Thorax. 2002 Jan;57(1):86-90 [11809997] Am J Respir Crit Care Med. 2002 Mar 1;165(5):683-9 [11874814] Br J Ind Med. 1981 Nov;38(4):334-8 [7032577] J Toxicol Environ Health. 1982 Feb;9(2):339-49 [7200524] J Toxicol Environ Health. 1982 Oct-Nov;10(4-5):613-9 [6891722] Clin Allergy. 1985 Nov;15(6):555-64 [4075515] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenicity of inhaled vanadium pentoxide in F344/N rats and B6C3F1 mice. AN - 73496013; 12773761 AB - Vanadium pentoxide (V2O5) is a slightly soluble compound found in airborne particle emissions from metallurgical works and oil and coal burning. Because the carcinogenic potential of V2O5 was not known, F344/N rats and B6C3F1 mice (N=50/sex/species) were exposed to V2O5 at concentrations of 0, 0.5 (rats only), 1, 2, or 4 (mice only) mg/m3, by whole-body inhalation for 2 years. The survival and body weights of rats were minimally affected by exposure to V2O5. The survival and body weights of male mice exposed to 4 mg/m3 and body weights of all exposed groups of female mice were lower than the controls. Alveolar/bronchiolar (A/B) neoplasms occurred in male rats exposed to 0.5 and 2 mg/m3 at incidences exceeding the National Toxicology Program (NTP) historical control ranges. A marginal increase in A/B neoplasms was also observed in female rats exposed to 0.5 mg/m3. Increases in chronic inflammation, interstitial fibrosis, and alveolar and bronchiolar hyperplasia/metaplasia and squamous metaplasia were observed in exposed male and female rats. A/B neoplasms were significantly increased in all groups of exposed mice. As with rats, increases in chronic inflammation, interstitial fibrosis, and alveolar and bronchiolar epithelial hyperplasia were observed in mice exposed to V2O5. Thus, V2O5 exposure was a pulmonary carcinogen in male rats and male and female mice. The marginal tumor response in the lungs of female rats could not be attributed conclusively to exposure to V2O5. These responses were noted at and slightly above the OSHA permissible occupational exposure limit of 0.5 mg/m3 (dust) (National Institute for Occupational Safety and Health, NIOSH Pocket Guide to Chemical Hazards, U.S. Department of Health and Human Services, Washington, DC, 1997, p. 328). JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Ress, N B AU - Chou, B J AU - Renne, R A AU - Dill, J A AU - Miller, R A AU - Roycroft, J H AU - Hailey, J R AU - Haseman, J K AU - Bucher, J R AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 287 EP - 296 VL - 74 IS - 2 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - Vanadium Compounds KW - vanadium pentoxide KW - BVG363OH7A KW - Index Medicus KW - Animals KW - Longevity -- drug effects KW - Mice KW - Respiratory System -- pathology KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Body Weight -- drug effects KW - Carcinogenicity Tests KW - Administration, Inhalation KW - Female KW - Male KW - Respiratory System -- drug effects KW - Carcinogens -- administration & dosage KW - Carcinoma -- pathology KW - Neoplasms, Experimental -- chemically induced KW - Vanadium Compounds -- toxicity KW - Adenoma -- chemically induced KW - Carcinogens -- toxicity KW - Vanadium Compounds -- administration & dosage KW - Lung Neoplasms -- chemically induced KW - Adenoma -- pathology KW - Lung Neoplasms -- pathology KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73496013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Carcinogenicity+of+inhaled+vanadium+pentoxide+in+F344%2FN+rats+and+B6C3F1+mice.&rft.au=Ress%2C+N+B%3BChou%2C+B+J%3BRenne%2C+R+A%3BDill%2C+J+A%3BMiller%2C+R+A%3BRoycroft%2C+J+H%3BHailey%2C+J+R%3BHaseman%2C+J+K%3BBucher%2C+J+R&rft.aulast=Ress&rft.aufirst=N&rft.date=2003-08-01&rft.volume=74&rft.issue=2&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-17 N1 - Date created - 2003-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-cycle structured intermittent versus continuous highly active antiretroviral therapy for the treatment of chronic infection with human immunodeficiency virus: effects on drug toxicity and on immunologic and virologic parameters. AN - 73492461; 12870120 AB - We evaluated the effect of long-cycle structured intermittent therapy (SIT; 4 weeks without highly active antiretroviral therapy [HAART] followed by 8 weeks with HAART) versus continuous HAART. The study was prematurely terminated to new enrollment because of the emergence of genetic mutations associated with resistance to antiretroviral drugs in 5 patients. After 48 weeks, there was no significant difference between groups in lipid, hepatic transaminase, and C-reactive protein levels in 41 patients. Although there were no differences in CD4(+) or CD8(+) T cell counts or the percentage of cells that were CD4(+)CD25(+), CD8(+)CD25(+), or CD4(+)DR(+), patients who received SIT had a significantly higher percentage of CD8(+)CD38(+) and CD8(+)DR(+) cells. There was no clear autoimmunization effect by immunologic or virologic parameters. There was no benefit to long-cycle SIT versus continuous HAART with regard to certain toxicity, immunologic, or virologic parameters. JF - The Journal of infectious diseases AU - Dybul, Mark AU - Nies-Kraske, Elizabeth AU - Daucher, Marybeth AU - Hertogs, Kurt AU - Hallahan, Claire W AU - Csako, Gyorgy AU - Yoder, Christian AU - Ehler, Linda AU - Sklar, Peter A AU - Belson, Michael AU - Hidalgo, Bertha AU - Metcalf, Julia A AU - Davey, Richard T AU - Rock Kress, Diane M AU - Powers, April AU - Fauci, Anthony S AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. mdybul@nih.gov. Y1 - 2003/08/01/ PY - 2003 DA - 2003 Aug 01 SP - 388 EP - 396 VL - 188 IS - 3 SN - 0022-1899, 0022-1899 KW - Anti-HIV Agents KW - 0 KW - Lipids KW - RNA, Viral KW - Receptors, Interleukin-2 KW - C-Reactive Protein KW - 9007-41-4 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Aminopeptidases KW - EC 3.4.11.- KW - Glutamyl Aminopeptidase KW - EC 3.4.11.7 KW - Abridged Index Medicus KW - Index Medicus KW - Lipids -- blood KW - Drug Administration Schedule KW - Receptors, Interleukin-2 -- analysis KW - Humans KW - Aminopeptidases -- blood KW - CD4-CD8 Ratio KW - C-Reactive Protein -- analysis KW - Lymphocyte Count KW - Alanine Transaminase -- blood KW - Drug Resistance, Viral KW - Treatment Outcome KW - Follow-Up Studies KW - T-Lymphocytes -- immunology KW - RNA, Viral -- analysis KW - Anti-HIV Agents -- therapeutic use KW - HIV Infections -- blood KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy KW - Antiretroviral Therapy, Highly Active KW - Anti-HIV Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73492461?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Long-cycle+structured+intermittent+versus+continuous+highly+active+antiretroviral+therapy+for+the+treatment+of+chronic+infection+with+human+immunodeficiency+virus%3A+effects+on+drug+toxicity+and+on+immunologic+and+virologic+parameters.&rft.au=Dybul%2C+Mark%3BNies-Kraske%2C+Elizabeth%3BDaucher%2C+Marybeth%3BHertogs%2C+Kurt%3BHallahan%2C+Claire+W%3BCsako%2C+Gyorgy%3BYoder%2C+Christian%3BEhler%2C+Linda%3BSklar%2C+Peter+A%3BBelson%2C+Michael%3BHidalgo%2C+Bertha%3BMetcalf%2C+Julia+A%3BDavey%2C+Richard+T%3BRock+Kress%2C+Diane+M%3BPowers%2C+April%3BFauci%2C+Anthony+S&rft.aulast=Dybul&rft.aufirst=Mark&rft.date=2003-08-01&rft.volume=188&rft.issue=3&rft.spage=388&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-16 N1 - Date created - 2003-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human papillomavirus: epidemiology and public health. AN - 73487323; 12873163 AB - Approximately 15 types of human papillomavirus (HPV) infection cause virtually all cases of cervical cancer. Human papillomavirus 16 is the major type, accounting for approximately 50% of cases. The major steps of cervical carcinogenesis include HPV infection, viral persistence and progression to precancer (as opposed to viral clearance), and invasion. Human papillomavirus is the most common sexually transmitted infection. However, most HPV infections become undetectable by even sensitive HPV DNA testing within 1 to 2 years. The prevalence of infection peaks at young ages and declines thereafter, perhaps as the result of HPV type-specific acquired immunity. Most HPV infections are neither microscopically evident nor visible, making HPV DNA detection the diagnostic reference standard. Poorly defined immunologic factors are the major determinants of viral outcome. Smoking, multiparity, and long-term oral contraceptive use increase the risk of persistence and progression. Other sexually transmitted infections (eg, Chlamydia trachomatis), chronic inflammation, and nutritional factors might also play a role. Overt, long-term viral persistence in the absence of precancer is uncommon. New prevention strategies can be derived from the evolving knowledge of HPV carcinogenesis. Human papillomavirus vaccination is the ultimate prevention strategy, and large-scale trials are already underway. In the meantime, HPV DNA diagnostics are more sensitive although less specific than cytology, permitting a consideration of lengthened screening intervals. In terms of public health education, clinicians and patients will need to shift discussions of the mildly abnormal Papanicolaou test to consideration of HPV infection as a common sexually transmitted infection that rarely causes cervical cancer. JF - Archives of pathology & laboratory medicine AU - Schiffman, Mark AU - Castle, Philip E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Md 20852, USA. schiffmm@mail.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 930 EP - 934 VL - 127 IS - 8 KW - Viral Vaccines KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Uterine Cervical Neoplasms -- prevention & control KW - Carrier State -- prevention & control KW - Humans KW - Carrier State -- transmission KW - Precancerous Conditions -- epidemiology KW - Precancerous Conditions -- virology KW - Penis -- virology KW - Skin -- virology KW - Uterine Cervical Neoplasms -- epidemiology KW - Risk Factors KW - Precancerous Conditions -- prevention & control KW - Carrier State -- epidemiology KW - Female KW - Male KW - Viral Vaccines -- therapeutic use KW - Uterine Cervical Neoplasms -- virology KW - Prevalence KW - Tumor Virus Infections -- transmission KW - Papillomavirus Infections -- epidemiology KW - Papillomaviridae -- pathogenicity KW - Papillomavirus Infections -- transmission KW - Papillomaviridae -- isolation & purification KW - Tumor Virus Infections -- epidemiology KW - Public Health -- education KW - Papillomavirus Infections -- prevention & control KW - Papillomaviridae -- immunology KW - Tumor Virus Infections -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73487323?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pathology+%26+laboratory+medicine&rft.atitle=Human+papillomavirus%3A+epidemiology+and+public+health.&rft.au=Schiffman%2C+Mark%3BCastle%2C+Philip+E&rft.aulast=Schiffman&rft.aufirst=Mark&rft.date=2003-08-01&rft.volume=127&rft.issue=8&rft.spage=930&rft.isbn=&rft.btitle=&rft.title=Archives+of+pathology+%26+laboratory+medicine&rft.issn=1543-2165&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-07 N1 - Date created - 2003-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-affinity partial agonists of the vanilloid receptor. AN - 73481577; 12869637 AB - The vanilloid receptor VR1 is a polymodal nociceptor sensitive to capsaicin, protons, and heat. Because VR1 represents an attractive therapeutic target for conditions ranging from long-term pain to bladder hyperreflexia, we and other groups have sought to develop novel ligands with enhanced potencies and novel pharmacological properties. Here, we characterize two compounds, N-[2-(3,4-dimethylbenzyl)-3-(pivaloyloxy)propyl]-N'-[4-(methylsulfonylamino)benzyl]thiourea (JYL827) and N-(4-tert-butylbenzyl)-N'-[3-methoxy-4-(methylsulfonylamino)benzyl]thiourea (JYL1511), that function as partial agonists for rat VR1 heterologously expressed in Chinese hamster ovary cells. Both compounds showed substantially enhanced potency, inhibiting [3H] resiniferatoxin binding with Ki values of 29.3 +/- 7.6 and 50.4 +/- 16.5 nM, respectively, compared with 1810 +/- 270 nM for capsaicin. The compounds showed different extents of partial agonism, 6.8 +/- 0.7% and 17.4 +/- 0.6%, respectively, and the expected corresponding degrees of partial antagonism (93.9 +/- 0.9 and 84.1 +/- 3.2%, respectively). Their IC50 values for antagonism of 45Ca2+ uptake in response to capsaicin were 67.3 +/- 24.9 nM and 3.4 +/- 0.5 nM, respectively. Protons, temperature, and protein kinase C all function as coactivators/modulators of rVR1. All enhanced the extent of partial agonism of JYL827 and JYL1511. Thus, at pH 5.5, for example, the extents of partial agonism increased to 54.9 +/- 2.5% and to 90.7 +/- 1.7%, respectively, relative to the response elicited by 300 nM capsaicin. The extents of partial antagonism decreased correspondingly. Compounds such as JYL827 and JYL1511 now permit exploration of the potential utility of partial agonists of rVR1 in animal models. Our results emphasize, moreover, the strong dependence of such partial agonists on other modulators of rVR1 and predict that their biological behavior will depend strongly on biological context. JF - Molecular pharmacology AU - Wang, Yun AU - Toth, Attila AU - Tran, Richard AU - Szabo, Tamas AU - Welter, Jacqueline D AU - Blumberg, Peter M AU - Lee, Jiyoun AU - Kang, Sang-Uk AU - Lim, Ju-Ok AU - Lee, Jeewoo AD - National Cancer Institute, Building 37, Room 4048, 37 Convent Drive MSC 4255, Bethesda, MD 20892-4255, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 325 EP - 333 VL - 64 IS - 2 SN - 0026-895X, 0026-895X KW - N-(2-(3,4-dimethylbenzyl)-3-(pivaloyloxy)propyl)-N'-(4-(methylsulfonylamino)benzyl)thiourea KW - 0 KW - N-(4-tert-butylbenzyl)-N'-(3-methoxy-4-(methylsulfonylamino)benzyl)thiourea KW - Protons KW - Receptors, Drug KW - Sulfonamides KW - Protein Kinase C KW - EC 2.7.11.13 KW - Thiourea KW - GYV9AM2QAG KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Signal Transduction -- physiology KW - Animals KW - Temperature KW - CHO Cells KW - Protein Kinase C -- physiology KW - Drug Synergism KW - Female KW - Cricetinae KW - Receptors, Drug -- agonists KW - Sulfonamides -- pharmacology KW - Thiourea -- pharmacology KW - Thiourea -- analogs & derivatives KW - Receptors, Drug -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73481577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=High-affinity+partial+agonists+of+the+vanilloid+receptor.&rft.au=Wang%2C+Yun%3BToth%2C+Attila%3BTran%2C+Richard%3BSzabo%2C+Tamas%3BWelter%2C+Jacqueline+D%3BBlumberg%2C+Peter+M%3BLee%2C+Jiyoun%3BKang%2C+Sang-Uk%3BLim%2C+Ju-Ok%3BLee%2C+Jeewoo&rft.aulast=Wang&rft.aufirst=Yun&rft.date=2003-08-01&rft.volume=64&rft.issue=2&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-15 N1 - Date created - 2003-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of Crm1 in hepatitis B virus X protein-induced aberrant centriole replication and abnormal mitotic spindles. AN - 73475827; 12861014 AB - Hepatitis B virus (HBV) includes an X gene (HBx gene) that plays a critical role in liver carcinogenesis. Because centrosome abnormalities are associated with genomic instability in most human cancer cells, we examined the effect of HBx on centrosomes. We found that HBx induced supernumerary centrosomes and multipolar spindles. This effect was independent of mutations in the p21 gene. Furthermore, the ability of HBV to induce supernumerary centrosomes was dependent on the presence of physiological HBx expression. We recently showed that HBx induces cytoplasmic sequestration of Crm1, a nuclear export receptor that binds to Ran GTPase, thereby inducing nuclear localization of NF-kappaB. Consistently, supernumerary centrosomes were observed in cells treated with a Crm1-specific inhibitor but not with an HBx mutant that lacked the ability to sequester Crm1 in the cytoplasm. Moreover, a fraction of Crm1 was found to be localized at the centrosomes. Immunocytochemical and ultrastructural examination of these supernumerary centrosomes revealed that inactivation of Crm1 was associated with abnormal centrioles. The presence of more than two centrosomes led to an increased frequency of defective mitoses and chromosome transmission errors. Based on this evidence, we suggest that Crm1 is actively involved in maintaining centrosome integrity and that HBx disrupts this process by inactivating Crm1 and thus contributes to HBV-mediated carcinogenesis. JF - Molecular and cellular biology AU - Forgues, Marshonna AU - Difilippantonio, Michael J AU - Linke, Steven P AU - Ried, Thomas AU - Nagashima, Kunio AU - Feden, Jeffrey AU - Valerie, Kristoffer AU - Fukasawa, Kenji AU - Wang, Xin W AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute/NIH, 37 Convent Drive, Bethesda, MD 20892, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 5282 EP - 5292 VL - 23 IS - 15 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - Fatty Acids, Unsaturated KW - Karyopherins KW - NF-kappa B KW - Receptors, Cytoplasmic and Nuclear KW - Trans-Activators KW - Tumor Suppressor Protein p53 KW - exportin 1 protein KW - hepatitis B virus X protein KW - DNA KW - 9007-49-2 KW - Telomerase KW - EC 2.7.7.49 KW - ran GTP-Binding Protein KW - EC 3.6.5.2 KW - rho GTP-Binding Proteins KW - leptomycin B KW - Y031I2N1EO KW - Index Medicus KW - Hepatitis B virus -- metabolism KW - Microscopy, Confocal KW - Cell Nucleus -- metabolism KW - Humans KW - In Situ Hybridization, Fluorescence KW - Centrosome KW - ran GTP-Binding Protein -- metabolism KW - Microscopy, Fluorescence KW - Cytoplasm -- metabolism KW - Mitosis KW - Cell Cycle KW - Time Factors KW - Active Transport, Cell Nucleus KW - Aneuploidy KW - Fluorescent Antibody Technique, Indirect KW - DNA -- metabolism KW - Fibroblasts -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Adenoviridae -- genetics KW - Blotting, Western KW - Fatty Acids, Unsaturated -- pharmacology KW - Mutation KW - Telomerase -- metabolism KW - rho GTP-Binding Proteins -- metabolism KW - NF-kappa B -- metabolism KW - Trans-Activators -- metabolism KW - Centrioles -- metabolism KW - Karyopherins -- physiology KW - Spindle Apparatus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73475827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Involvement+of+Crm1+in+hepatitis+B+virus+X+protein-induced+aberrant+centriole+replication+and+abnormal+mitotic+spindles.&rft.au=Forgues%2C+Marshonna%3BDifilippantonio%2C+Michael+J%3BLinke%2C+Steven+P%3BRied%2C+Thomas%3BNagashima%2C+Kunio%3BFeden%2C+Jeffrey%3BValerie%2C+Kristoffer%3BFukasawa%2C+Kenji%3BWang%2C+Xin+W&rft.aulast=Forgues&rft.aufirst=Marshonna&rft.date=2003-08-01&rft.volume=23&rft.issue=15&rft.spage=5282&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 - 2003-08-29 N1 - Date created - 2003-07-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Curr Biol. 1999 Oct 7;9(19):1107-10 [10531007] Biol Cell. 1999 Jul;91(6):413-27 [10519003] J Gastroenterol Hepatol. 2000 Apr;15(4):339-41 [10824873] J Gastroenterol Hepatol. 2000 Apr;15(4):357-68 [10824878] Semin Cancer Biol. 2000 Jun;10(3):211-31 [10936070] Cell Growth Differ. 2000 Aug;11(8):455-65 [10965850] Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10002-7 [10944189] Curr Top Dev Biol. 2000;49:313-29 [11005025] Cell. 2000 Sep 29;103(1):127-40 [11051553] Trends Cell Biol. 2001 Jan;11(1):18-21 [11146294] Cell. 2001 Jan 12;104(1):83-93 [11163242] Cell. 2001 Jan 12;104(1):95-106 [11163243] Cell. 2001 Feb 9;104(3):321-4 [11239388] Nat Cell Biol. 2001 Apr;3(4):429-32 [11283619] Nat Cell Biol. 2001 Apr;3(4):433-8 [11283620] Cancer Res. 2001 Mar 15;61(6):2356-60 [11289095] J Biol Chem. 2001 Jun 22;276(25):22797-803 [11287420] Oncogene. 2001 Jun 21;20(28):3674-82 [11439330] Nat Rev Mol Cell Biol. 2001 Sep;2(9):688-98 [11533726] J Gastroenterol. 2001 Oct;36(10):651-60 [11686474] Science. 2001 Dec 14;294(5550):2376-8 [11743208] FASEB J. 2002 Oct;16(12):1665-7 [12207007] Nat Rev Cancer. 2002 Nov;2(11):815-25 [12415252] Cell. 1991 Jul 26;66(2):347-60 [1855255] J Cell Biol. 1993 Jun;121(5):961-76 [8388878] Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11215-9 [7479968] Cancer Res. 1995 Dec 15;55(24):6012-6 [8521383] Science. 1996 Mar 22;271(5256):1744-7 [8596939] Intervirology. 1995;38(3-4):134-42 [8682608] Hepatology. 1997 Apr;25(4):1037-8 [9096618] Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14707-12 [9405677] J Virol. 1998 Mar;72(3):1737-43 [9499022] Science. 1998 Nov 20;282(5393):1497-501 [9822382] Mol Cell. 1999 Mar;3(3):389-95 [10198641] Science. 1999 May 21;284(5418):1356-8 [10334990] Science. 1999 May 21;284(5418):1359-62 [10334991] Nature. 1999 Jul 8;400(6740):178-81 [10408446] J Cell Physiol. 1999 Nov;181(2):188-202 [10497299] Nat Genet. 1999 Oct;23(2):176-84 [10508513] Carcinogenesis. 2000 Mar;21(3):405-26 [10688861] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distribution and toxicity resulting from adenoviral vector administration to a single salivary gland in adult rats. AN - 73463763; 12846788 AB - We examined the distribution and toxicity associated with a single salivary gland administration of a recombinant adenoviral vector, AdCMVH3, encoding human histatin 3. Adult rats received different doses of AdCMVH3 (0, 106, 3 x 107, and 109 pfu; 50 microl) via the right submandibular gland and were followed for 15 days. Food consumption, weight gain, clinical appearance, and serum chemistry were monitored, and a necropsy was performed. Vector distribution was examined by polymerase chain reaction, and selected saliva samples were tested for replication-competent adenovirus (RCA). All animals survived to sacrifice (days 2, 8, and 15), and appeared normal clinically. There were no differences in food consumption, weight gain, and serum chemistry. The only consistent necropsy findings were lymphoid infiltrates and necrosis in the target submandibular glands of high-dosage animals. AdCMVH3 detection was virus dose dependent, decreased with time, and at low dose preferentially observed in the targeted gland. No RCA was detected. Salivary gland administration of 109 pfu AdCMVH3 elicits an initial focal pathologic response and wide tissue distribution. There is no associated systemic toxicity up to 15 days, and lower doses are primarily found in glands. JF - Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology AU - O'Connell, Brian C AU - Zheng, Changyu AU - Jacobson-Kram, David AU - Baum, Bruce J AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 414 EP - 421 VL - 32 IS - 7 SN - 0904-2512, 0904-2512 KW - Glycoproteins KW - 0 KW - HTN3 protein, human KW - Histatins KW - Proteins KW - Recombinant Proteins KW - Salivary Proteins and Peptides KW - Dentistry KW - Index Medicus KW - Rats KW - Eating KW - Animals KW - Blood Chemical Analysis KW - Random Allocation KW - Saliva -- chemistry KW - Humans KW - Tissue Distribution KW - Weight Gain KW - Male KW - Female KW - Genetic Vectors -- administration & dosage KW - Submandibular Gland -- pathology KW - Submandibular Gland -- metabolism KW - Salivary Proteins and Peptides -- genetics KW - Genetic Vectors -- pharmacokinetics KW - Glycoproteins -- genetics KW - Proteins -- genetics KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73463763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oral+pathology+%26+medicine+%3A+official+publication+of+the+International+Association+of+Oral+Pathologists+and+the+American+Academy+of+Oral+Pathology&rft.atitle=Distribution+and+toxicity+resulting+from+adenoviral+vector+administration+to+a+single+salivary+gland+in+adult+rats.&rft.au=O%27Connell%2C+Brian+C%3BZheng%2C+Changyu%3BJacobson-Kram%2C+David%3BBaum%2C+Bruce+J&rft.aulast=O%27Connell&rft.aufirst=Brian&rft.date=2003-08-01&rft.volume=32&rft.issue=7&rft.spage=414&rft.isbn=&rft.btitle=&rft.title=Journal+of+oral+pathology+%26+medicine+%3A+official+publication+of+the+International+Association+of+Oral+Pathologists+and+the+American+Academy+of+Oral+Pathology&rft.issn=09042512&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-27 N1 - Date created - 2003-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The nitric oxide donor, V-PYRRO/NO, protects against acetaminophen-induced nephrotoxicity in mice. AN - 73444355; 12832150 AB - The nitric oxide (NO) donor, O(2)-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO), is metabolized by P450 enzymes to release NO in the liver and possibly other tissues. V-PYRRO/NO has been shown to be hepatoprotective, but little is known about its effect in the kidney, another organ rich in P450s. Thus, mice were given V-PYRRO/NO (0.4-5.4 mg/ml, 8 microl/h) before and/or after a nephrotoxic dose of acetaminophen (APAP; 600 mg/kg, i.p.) to examine its nephroprotective effects. V-PYRRO/NO administration significantly reduced APAP-induced nephrotoxicity in a dose- and time-dependent manner, as evidenced by mitigation of increased blood urea nitrogen levels and by amelioration of renal pathology, specifically interstitial congestion, proximal tubular cell degeneration and necrosis. The best protection was observed at the highest dose (5.4 mg/ml) and with V-PYRRO/NO pretreatment (4-16 h). Implanting V-PYRRO/NO pumps simultaneously with APAP also attenuated APAP nephrotoxicity. The protection is probably not due to a decreased APAP toxication metabolism, as similar depletion of renal glutathione levels was observed regardless of V-PYRRO/NO treatment. APAP-induced renal lipid peroxidation was reduced by V-PYRRO/NO, as determined by the concentrations of hydroxynonenals and malondialdehyde. In summary, this study demonstrates that the NO donor V-PYRRO/NO is effective in blocking APAP-induced nephrotoxicity in mice. The protection is probably due to multiple mechanisms involving attenuation of APAP-induced congestion and lipid peroxidation in the kidney. JF - Toxicology AU - Li, Chengxiu AU - Liu, Jie AU - Saavedra, Joseph E AU - Keefer, Larry K AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27706, USA. Y1 - 2003/08/01/ PY - 2003 DA - 2003 Aug 01 SP - 173 EP - 180 VL - 189 IS - 3 SN - 0300-483X, 0300-483X KW - Analgesics, Non-Narcotic KW - 0 KW - Lipid Peroxides KW - Nitric Oxide Donors KW - O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate KW - Pyrrolidines KW - Acetaminophen KW - 362O9ITL9D KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Glutathione -- metabolism KW - Mice KW - Histocytochemistry KW - Blood Urea Nitrogen KW - Lipid Peroxides -- metabolism KW - Female KW - Nitric Oxide Donors -- pharmacology KW - Analgesics, Non-Narcotic -- antagonists & inhibitors KW - Analgesics, Non-Narcotic -- toxicity KW - Pyrrolidines -- pharmacology KW - Kidney Diseases -- prevention & control KW - Acetaminophen -- antagonists & inhibitors KW - Acetaminophen -- toxicity KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73444355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=The+nitric+oxide+donor%2C+V-PYRRO%2FNO%2C+protects+against+acetaminophen-induced+nephrotoxicity+in+mice.&rft.au=Li%2C+Chengxiu%3BLiu%2C+Jie%3BSaavedra%2C+Joseph+E%3BKeefer%2C+Larry+K%3BWaalkes%2C+Michael+P&rft.aulast=Li&rft.aufirst=Chengxiu&rft.date=2003-08-01&rft.volume=189&rft.issue=3&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-05 N1 - Date created - 2003-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adjacent sequence controls the response polarity of nitric oxide-sensitive Sp factor binding sites. AN - 73443727; 12759366 AB - Nitric oxide (NO*) and cAMP-dependent protein kinase (PKA) inhibitors up-regulate tumor necrosis factor alpha (TNFalpha) by decreasing Sp1 binding to a proximal GC box element. Here, elements flanking GC boxes were tested for their role in determining whether Sp sites act as activators or repressors. Promoter studies in receptive human cell lines demonstrated that NO* down-regulated endothelial NO* synthase (eNOS) but up-regulated TNFalpha. Like TNFalpha, Sp1 binding to the eNOS promoter was decreased by NO* and a PKA inhibitor, H89, and increased by a PKA activator, dibutyryl cAMP (Bt2cAMP). For either promoter, mutation of Sp sites abolished NO* responses. In contrast, mutation of an upstream AP1 site in the TNFalpha promoter (not present in eNOS) maintained NO* responsiveness, but reversed the direction of NO* and cAMP effects. Using artificial constructs, NO* increased transcription when Sp and AP1 sites were both present (TNFalpha-like response), but decreased it when the adjacent AP1 site was disrupted (eNOS-like response). NO*, H89, and Bt2cAMP were found to produce reciprocal protein binding changes at contiguous AP1 and Sp sites (p < 0.0001 for an interaction). Chromatin immunoprecipitation assays demonstrated that Sp1 and to a lesser extent Sp3 bound to the GC box regions of eNOS and TNFalpha in intact cells. Thus, this NO*- and cAMP-responsive regulatory module has a Sp site sensor variably coupled to an adjacent element that determines response polarity. These results define a composite element that can utilize secondary inputs to convert off signals to on, thereby conferring complex functionalities to the same DNA binding motif. JF - The Journal of biological chemistry AU - Zhang, Jianhua AU - Wang, Shuibang AU - Wesley, Robert A AU - Danner, Robert L AD - Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/08/01/ PY - 2003 DA - 2003 Aug 01 SP - 29192 EP - 29200 VL - 278 IS - 31 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Enzyme Inhibitors KW - Isoquinolines KW - SP3 protein, human KW - Sp1 Transcription Factor KW - Sulfonamides KW - Transcription Factor AP-1 KW - Transcription Factors KW - Tumor Necrosis Factor-alpha KW - Sp3 Transcription Factor KW - 148710-94-5 KW - Nitric Oxide KW - 31C4KY9ESH KW - Bucladesine KW - 63X7MBT2LQ KW - DNA KW - 9007-49-2 KW - NOS3 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type III KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide KW - M876330O56 KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Transcription Factors -- metabolism KW - Transcription Factor AP-1 -- metabolism KW - Humans KW - Bucladesine -- pharmacology KW - Tumor Necrosis Factor-alpha -- genetics KW - Mutagenesis, Site-Directed KW - Isoquinolines -- pharmacology KW - Promoter Regions, Genetic KW - Base Sequence KW - Transfection KW - Nitric Oxide Synthase -- genetics KW - Enzyme Activation -- drug effects KW - Cyclic AMP-Dependent Protein Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Tumor Necrosis Factor-alpha -- metabolism KW - Nitric Oxide Synthase -- metabolism KW - Cell Line KW - DNA-Binding Proteins -- metabolism KW - DNA -- metabolism KW - Sp1 Transcription Factor -- metabolism KW - Nitric Oxide -- pharmacology KW - DNA -- chemistry KW - Binding Sites UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73443727?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Adjacent+sequence+controls+the+response+polarity+of+nitric+oxide-sensitive+Sp+factor+binding+sites.&rft.au=Zhang%2C+Jianhua%3BWang%2C+Shuibang%3BWesley%2C+Robert+A%3BDanner%2C+Robert+L&rft.aulast=Zhang&rft.aufirst=Jianhua&rft.date=2003-08-01&rft.volume=278&rft.issue=31&rft.spage=29192&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 - 2003-09-10 N1 - Date created - 2003-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neoplastic development in plasma cells. AN - 73437119; 12846815 AB - An increasing number of model systems of plasma cell tumor (PCT) formation have been and are being developed. Discussed here are six models in mice and multiple myeloma (MM) in humans. Each model illustrates a unique set of biological factors. There are two general types of model systems: those that depend upon naturally arising mutagenic changes (pristane-induced PCTs, 5TMM, and MM) and those that are associated with oncogenes (Emu-v-abl), growth factors [interleukin-6 (IL-6)], and anti-apoptotic factors (Bcl-xL/Bcl-2). PCTs develop in several special tissue microenvironments that provide essential cytokines (IL-6) and cell-cell interactions. In mice, the activation and deregulation of c-myc by chromosomal translocations is a major feature in many of the models. This mechanism is much less a factor in MM and the 5T model in mice. Genetically determined susceptibility is involved in many of the mouse models, but only a few genes have been implicated thus far. JF - Immunological reviews AU - Potter, Michael AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. potter@helix.nih.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 177 EP - 195 VL - 194 SN - 0105-2896, 0105-2896 KW - Index Medicus KW - Animals KW - Multiple Myeloma -- pathology KW - Humans KW - Paraproteinemias -- pathology KW - Mice KW - Mice, Transgenic KW - Inflammation -- complications KW - Inflammation -- pathology KW - Plasma Cells -- metabolism KW - Plasma Cells -- cytology KW - Plasma Cells -- pathology KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73437119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunological+reviews&rft.atitle=Neoplastic+development+in+plasma+cells.&rft.au=Potter%2C+Michael&rft.aulast=Potter&rft.aufirst=Michael&rft.date=2003-08-01&rft.volume=194&rft.issue=&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Immunological+reviews&rft.issn=01052896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-10 N1 - Date created - 2003-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of constitutive androstane receptor and glucocorticoid receptor binding sites in the CYP2C19 promoter. AN - 73430401; 12869636 AB - CYP2C19 is an important human drug-metabolizing enzyme that metabolizes a number of clinically used drugs including the antiulcer drug omeprazole, the anxiolytic drug diazepam, the beta-blocker propranolol, the antimalarial drug proguanil, certain antidepressants and barbiturates, and the prototype substrate S-mephenytoin. Previous studies show that compounds such as rifampicin and dexamethasone induce CYP2C19 both in vivo in humans and in vitro in human hepatocytes. This study examines the transcriptional regulation of CYP2C19. Analysis of the CYP2C19 promoter revealed a single constitutive androstane receptor (CAR) binding site (CAR-RE; -1891/-1876 bp) and a glucocorticoid-responsive element (GRE; -1750/-1736 bp). Gel-shift assays showed that CAR-RE binds CAR and pregnane X receptor (PXR). Cotransfection with hCAR, mCAR, or hPXR in HepG2 cells up-regulated transcription of CYP2C19 promoter constructs, whereas mutation of the -1891-bp CAR-RE abolished up-regulation. Expression with hCAR also up-regulated endogenous CYP2C19 mRNA content in HepG2 cells. Androstenol repressed the mCAR-mediated constitutive activation of the CYP2C19 promoter in HepG2 cells, whereas the potent mCAR ligand 1,4-bis[2-3,5-dichloropyridyloxyl)] benzene derepressed this response. Rifampicin produced a modest increase in promoter activity in cells cotransfected with hPXR. Dexamethasone activated the -2.7-kb CYP2C19 promoter constructs in HepG2 cells only in the presence of cotransfected glucocorticoid receptor (GR), whereas the GR antagonist mifepristone inhibits this response. Mutation of the GRE abolishes dexamethasone activation. This is the first study to identify nuclear receptor binding sites (CAR/PXR and GR) in the CYP2C19 promoter and to suggest that these receptors may up-regulate CYP2C19 constitutively and possibly its response to drugs. JF - Molecular pharmacology AU - Chen, Yuping AU - Ferguson, Stephen S AU - Negishi, Masahiko AU - Goldstein, Joyce A AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 316 EP - 324 VL - 64 IS - 2 SN - 0026-895X, 0026-895X KW - DNA-Binding Proteins KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Glucocorticoid KW - Transcription Factors KW - constitutive androstane receptor KW - Mifepristone KW - 320T6RNW1F KW - Dexamethasone KW - 7S5I7G3JQL KW - Mixed Function Oxygenases KW - EC 1.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2C19 protein, human KW - Cytochrome P-450 CYP2C19 KW - Index Medicus KW - Drug Interactions KW - Tumor Cells, Cultured KW - Enzyme Activation KW - Cells, Cultured KW - Humans KW - Dexamethasone -- pharmacology KW - Dexamethasone -- antagonists & inhibitors KW - Mifepristone -- pharmacology KW - DNA-Binding Proteins -- metabolism KW - Binding Sites KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Promoter Regions, Genetic -- physiology KW - Aryl Hydrocarbon Hydroxylases -- metabolism KW - Mixed Function Oxygenases -- metabolism KW - Promoter Regions, Genetic -- drug effects KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Aryl Hydrocarbon Hydroxylases -- genetics KW - Receptors, Glucocorticoid -- metabolism KW - Mixed Function Oxygenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73430401?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Identification+of+constitutive+androstane+receptor+and+glucocorticoid+receptor+binding+sites+in+the+CYP2C19+promoter.&rft.au=Chen%2C+Yuping%3BFerguson%2C+Stephen+S%3BNegishi%2C+Masahiko%3BGoldstein%2C+Joyce+A&rft.aulast=Chen&rft.aufirst=Yuping&rft.date=2003-08-01&rft.volume=64&rft.issue=2&rft.spage=316&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-15 N1 - Date created - 2003-07-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Are dopamine antagonists a risk factor for breast cancer? An answer from Parkinson's disease. AN - 71476769; 14659314 AB - Women undergoing chemotherapy for breast cancer are often administered dopamine antagonist adjuvant medications that may increase levels of prolactin potentially increasing the risk of cancer. Using nationwide computerized registers of death data for the years 1991 through 1996 we examined 12,430,473 deaths of persons over 40 years of age and extracted 144,364 cases with Parkinson's disease (PD), a dopamine deficient population. Patients with PD had lower rates of breast and other types of malignancies, even in the presence of depression and suicide. JF - Breast (Edinburgh, Scotland) AU - Lalonde, François M AU - Myslobodsky, Michael AD - Geriatric Psychiatry Branch, NIMH, NIH, Bethesda, MD, USA. Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 280 EP - 282 VL - 12 IS - 4 SN - 0960-9776, 0960-9776 KW - Antipsychotic Agents KW - 0 KW - Dopamine Antagonists KW - Prolactin KW - 9002-62-4 KW - Index Medicus KW - Antipsychotic Agents -- therapeutic use KW - Humans KW - Retrospective Studies KW - Aged KW - Risk Assessment KW - Age Distribution KW - Registries KW - Aged, 80 and over KW - Adult KW - Incidence KW - Follow-Up Studies KW - Middle Aged KW - Antipsychotic Agents -- adverse effects KW - Psychotic Disorders -- diagnosis KW - United States -- epidemiology KW - Female KW - Psychotic Disorders -- drug therapy KW - Prolactin -- blood KW - Dopamine Antagonists -- therapeutic use KW - Breast Neoplasms -- diagnosis KW - Dopamine Antagonists -- adverse effects KW - Breast Neoplasms -- epidemiology KW - Breast Neoplasms -- chemically induced KW - Parkinson Disease -- drug therapy KW - Parkinson Disease -- epidemiology KW - Parkinson Disease -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71476769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+%28Edinburgh%2C+Scotland%29&rft.atitle=Are+dopamine+antagonists+a+risk+factor+for+breast+cancer%3F+An+answer+from+Parkinson%27s+disease.&rft.au=Lalonde%2C+Fran%C3%A7ois+M%3BMyslobodsky%2C+Michael&rft.aulast=Lalonde&rft.aufirst=Fran%C3%A7ois&rft.date=2003-08-01&rft.volume=12&rft.issue=4&rft.spage=280&rft.isbn=&rft.btitle=&rft.title=Breast+%28Edinburgh%2C+Scotland%29&rft.issn=09609776&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-06 N1 - Date created - 2003-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Renal development: perspectives on a Wnt-dependent process. AN - 71378011; 14627118 AB - Specification of embryonic progenitors to generate the branched collecting duct system and tubular epithelia of the nephron in the metanephros is mediated by families of soluble factors that cooperate to regulate morphogenesis. These include multiple members of the FGF, TGF-beta, and Wnt families; however, the complexity of interactions through cell-cell and extracellular matrix-mediated contacts, the redundancy of factors involved, and multiplicity of cooperative signaling mechanisms limit our understanding of events responsible for this development. With available in vitro and targeted mutagenesis models, we are now beginning to comprehend how the secreted inductive proteins and associated transcription factors direct competent cells to produce a functional filtering tubular epithelium and its tightly integrated vascular network. JF - Seminars in cell & developmental biology AU - Perantoni, Alan O AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute--Frederick, Frederick, MD 21702, USA. peranton@mail.ncifcrf.gov Y1 - 2003/08// PY - 2003 DA - August 2003 SP - 201 EP - 208 VL - 14 IS - 4 SN - 1084-9521, 1084-9521 KW - Proto-Oncogene Proteins KW - 0 KW - Wnt Proteins KW - Zebrafish Proteins KW - Fibroblast Growth Factors KW - 62031-54-3 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Ureter -- metabolism KW - Animals KW - Extracellular Matrix -- metabolism KW - Humans KW - Cell Communication KW - Fibroblast Growth Factors -- metabolism KW - Time Factors KW - Models, Biological KW - Signal Transduction KW - Mutagenesis KW - Nephrons -- embryology KW - Kidney -- metabolism KW - Nephrons -- metabolism KW - Kidney -- embryology KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71378011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell+%26+developmental+biology&rft.atitle=Renal+development%3A+perspectives+on+a+Wnt-dependent+process.&rft.au=Perantoni%2C+Alan+O&rft.aulast=Perantoni&rft.aufirst=Alan&rft.date=2003-08-01&rft.volume=14&rft.issue=4&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Seminars+in+cell+%26+developmental+biology&rft.issn=10849521&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-12 N1 - Date created - 2003-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Agar-plated bacteria found in the activated sludge of lab-scale SBR and CFSTR systems AN - 19770377; 5899346 AB - We identified and compared the predominant agar-plated bacteria in the activated sludge of two popular wastewater treatment systems, the sequencing batch reactor (SBR) and the continuous-flow stirred tank reactor (CFSTR). All tests had the same feed composition except for the buffer intensity. It was found that Corynebacterium sp. seemed to prefer growing under lower buffer condition, and Arthrobacter sp. grew dominantly in the system with higher buffer intensity. Gram-negative bacteria appeared more sensitive to an environment with unstable organic loading, such as in the SBR system. On the contrary, the SBR system was more selective to the Gram-positive genera with a special rod-coccus-cycle characteristic, such as Arthrobacter, Corynebacterium, or Brevibacterium. JF - Bioresource Technology AU - Juang, D-F AU - Hwu, C-S AD - Department of Healthcare Administration, Mei-Ho Institute of Technology, 23, Ping-Kuang Road, Nei Pu, Ping Tong 912, Taiwan, ROC, x2060@email.meiho.edu.tw Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 75 EP - 79 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 89 IS - 1 SN - 0960-8524, 0960-8524 KW - Microbiology Abstracts B: Bacteriology; Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Agricultural and Environmental Biotechnology Abstracts; Water Resources Abstracts; Aqualine Abstracts KW - Activated Sludge KW - Bacteria KW - Activated sludge KW - Arthrobacter KW - AQ 00006:Sewage KW - SW 3040:Wastewater treatment processes KW - A 01105:Non-patents KW - W2 32510:Waste treatment, environment, pollution KW - W 30965:Miscellaneous, Reviews KW - W4 210:Bioremediation, Bioreactors & BioCycling KW - J 02300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19770377?accountid=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=Bioresource+Technology&rft.atitle=Agar-plated+bacteria+found+in+the+activated+sludge+of+lab-scale+SBR+and+CFSTR+systems&rft.au=Juang%2C+D-F%3BHwu%2C+C-S&rft.aulast=Juang&rft.aufirst=D-F&rft.date=2003-08-01&rft.volume=89&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Bioresource+Technology&rft.issn=09608524&rft_id=info:doi/10.1016%2FS0960-8524%2803%2900007-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2004-09-01 N1 - Last updated - 2014-02-11 N1 - SubjectsTermNotLitGenreText - Activated sludge; Bacteria; Arthrobacter DO - http://dx.doi.org/10.1016/S0960-8524(03)00007-5 ER - TY - JOUR T1 - Temperature, Air Pollution, and Hospitalization for Cardiovascular Diseases among Elderly People in Denver AN - 19398402; 5711825 AB - Daily measures of maximum temperature, particulate matter less than or equal to 10 mu m in aerodynamic diameter (PM sub(10)), and gaseous pollution (ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide) were collected in Denver, Colorado, in July and August between 1993 and 1997. We then compared these exposures with concurrent data on the number of daily hospital admissions for cardiovascular diseases in men and women > 65 years of age. Generalized linear models, assuming a Poisson error structure for the selected cardiovascular disease hospital admissions, were constructed to evaluate the associations with air pollution and temperature. After adjusting the admission data for yearly trends, day-of-week effects, ambient maximum temperature, and dew point temperature, we studied the associations of the pollutants in single-pollutant models with lag times of 0-4 days. The results suggest that O sub(3) is associated with an increase in the risk of hospitalization for acute myocardial infarction, coronary atherosclerosis, and pulmonary heart disease. SO sub(2) appears to be related to increased hospital stays for cardiac dysrhythmias, and CO is significantly associated with congestive heart failure. No association was found between particulate matter or NO sub(2) and any of the health outcomes. Males tend to have higher numbers of hospital admissions than do females for all of the selected cardiovascular diseases, except for congestive heart failure. Higher temperatures appear to be an important factor in increasing the frequency of hospitalization for acute myocardial infarction and congestive heart failure, and are associated with a decrease in the frequency of visits for coronary atherosclerosis and pulmonary heart disease. JF - Environmental Health Perspectives AU - Koken, PJM AU - Piver, W T AU - Ye, F AU - Elixhauser, A AU - Olsen, L M AU - Portier, C J AD - National Institute of Environmental Health Sciences, MD A3-06, PO Box 12233, Research Triangle Park, NC 27709, USA, koken@niehs.nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 1312 EP - 1317 PB - NIH, Government Printing Office VL - 111 IS - 10 SN - 0091-6765, 0091-6765 KW - elderly KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts; Meteorological & Geoastrophysical Abstracts KW - Atmospheric pollution models KW - Cardiovascular system KW - Environmental health KW - Particulates KW - Nitrogen dioxide KW - Carbon monoxide KW - Sulfur dioxide KW - Maximum temperatures KW - USA, Colorado, Denver KW - Atmospheric pollution and health KW - Geriatrics KW - Diseases KW - Ozone KW - Temperature effects KW - Atmospheric pollution KW - Coronal studies KW - Temperature KW - Particulate atmospheric pollution KW - Air pollution KW - USA, Colorado KW - Temperature trends KW - Cardiovascular diseases KW - Dew point temperatures KW - Hospitals KW - M2 551.510.42:Air Pollution (551.510.42) KW - X 24156:Environmental impact KW - H 12000:Epidemiology and Public Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19398402?accountid=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=Temperature%2C+Air+Pollution%2C+and+Hospitalization+for+Cardiovascular+Diseases+among+Elderly+People+in+Denver&rft.au=Koken%2C+PJM%3BPiver%2C+W+T%3BYe%2C+F%3BElixhauser%2C+A%3BOlsen%2C+L+M%3BPortier%2C+C+J&rft.aulast=Koken&rft.aufirst=PJM&rft.date=2003-08-01&rft.volume=111&rft.issue=10&rft.spage=1312&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Fehp.5957 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-02-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Temperature effects; Air pollution; Cardiovascular system; Geriatrics; Diseases; Coronal studies; Atmospheric pollution; Maximum temperatures; Atmospheric pollution models; Atmospheric pollution and health; Temperature trends; Cardiovascular diseases; Dew point temperatures; Particulate atmospheric pollution; Ozone; Carbon monoxide; Nitrogen dioxide; Sulfur dioxide; Temperature; Environmental health; Particulates; Hospitals; USA, Colorado; USA, Colorado, Denver DO - http://dx.doi.org/10.1289/ehp.5957 ER - TY - JOUR T1 - Applying molecular genetic tools to the conservation and action plan for the critically endangered Far Eastern leopard (Panthera pardus orientalis) AN - 19261950; 5821554 AB - A role for molecular genetic approaches in conservation of endangered taxa is now commonly recognized. Because conservation genetic analyses provide essential insights on taxonomic status, recent evolutionary history and current health of endangered taxa, they are considered in nearly all conservation programs. Genetic analyses of the critically endangered Far Eastern, or Amur leopard, Panthera pardus orientalis, have been done recently to address all of these questions and develop strategies for survival of the leopard in the wild. The genetic status and implication for conservation management of the Far Eastern leopard subspecies are discussed. JF - Comptes Rendus Biologies AU - Uphyrkina, O AU - O'Brien, S J AD - Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702-1201, USA, obrien@ncifcrf.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - S93 EP - S97 VL - 326 SN - 1631-0691, 1631-0691 KW - Leopard KW - Genetics Abstracts; Ecology Abstracts KW - Survival KW - Conservation genetics KW - Panthera pardus orientalis KW - Evolution KW - G 07405:Carnivora KW - D 04705:Conservation KW - G 07260:Taxonomy, systematics and evolutionary genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19261950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Comptes+Rendus+Biologies&rft.atitle=Applying+molecular+genetic+tools+to+the+conservation+and+action+plan+for+the+critically+endangered+Far+Eastern+leopard+%28Panthera+pardus+orientalis%29&rft.au=Uphyrkina%2C+O%3BO%27Brien%2C+S+J&rft.aulast=Uphyrkina&rft.aufirst=O&rft.date=2003-08-01&rft.volume=326&rft.issue=&rft.spage=S93&rft.isbn=&rft.btitle=&rft.title=Comptes+Rendus+Biologies&rft.issn=16310691&rft_id=info:doi/10.1016%2FS1631-0691%2803%2900044-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Panthera pardus orientalis; Evolution; Conservation genetics; Survival DO - http://dx.doi.org/10.1016/S1631-0691(03)00044-1 ER - TY - JOUR T1 - Haya Lorberboum-Galski and Philip Lazarovici (Eds.). Chimeric Toxins: Mechanisms of Action and Therapeutic Applications (Cell and Molecular Mechanisms of Toxin Action) AN - 19218494; 5773740 JF - International Journal of Toxicology AU - Youle, R J AD - Surgical Neurology Branch, NINDS, NIH, Bethesda, MD, USA Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 331 EP - 332 VL - 22 IS - 4 SN - 1091-5818, 1091-5818 KW - mechanisms KW - chimeric toxins KW - Toxicology Abstracts KW - Reviews KW - Toxins KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19218494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Toxicology&rft.atitle=Haya+Lorberboum-Galski+and+Philip+Lazarovici+%28Eds.%29.+Chimeric+Toxins%3A+Mechanisms+of+Action+and+Therapeutic+Applications+%28Cell+and+Molecular+Mechanisms+of+Toxin+Action%29&rft.au=Youle%2C+R+J&rft.aulast=Youle&rft.aufirst=R&rft.date=2003-08-01&rft.volume=22&rft.issue=4&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Toxicology&rft.issn=10915818&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; Toxins ER - TY - JOUR T1 - Phenotypic characterization of overexpression or deletion of the Escherichia coli crcA, cspE and crcB genes AN - 19190752; 5765361 AB - The authors have previously shown that overexpression of the Escherichia coli K-12 crcA, cspE and crcB genes protects the chromosome from decondensation by camphor. In this study they examine the phenotypic consequences of deleting or overexpressing crcA, cspE and crcB. Overexpressing crcA, cspE and crcB increases supercoiling levels of plasmids in wild-type cells and in temperature-sensitive (Ts) gyrase mutants, suppresses the sensitivity of gyrase and topoisomerase IV (topo IV) Ts mutants to nalidixic acid, makes gyrase and topo IV Ts mutants more resistant to camphor and corrects the nucleoid morphology defects in topo IV Ts mutants. Overexpression of crcA, cspE and crcB results in a slight (2 times 2-fold) activation of the rcsA gene. Deleting crcA, cspE and crcB is not lethal to cells but results in an increase in sensitivity to camphor. Deletion of crcA, cspE and crcB exacerbates the nucleoid morphology defects of the topo IV Ts mutants. When the individual crcA, cspE or crcB genes were tested for their effects on camphor resistance and regulation of rcsA, cspE alone conferred 10-fold camphor resistance and 1 times 7-fold activation of rcsA. These activities were augmented when crcB was overexpressed with cspE (100-fold camphor resistance and 2 times 1-fold induction of rcsA). JF - Microbiology AU - Sand, O AU - Gingras, M AU - Beck, N AU - Hall, C AU - Trun, N AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA, trun@duq.edu Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 2107 EP - 2117 VL - 149 IS - 8 SN - 1350-0872, 1350-0872 KW - camphor KW - crcA gene KW - crcB gene KW - cspE gene KW - Microbiology Abstracts B: Bacteriology KW - Deletion mutant KW - Supercoiling KW - Overexpression KW - Genetic analysis KW - DNA topoisomerase KW - Escherichia coli KW - Stress KW - Plasmids KW - DNA topoisomerase IV KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19190752?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbiology&rft.atitle=Phenotypic+characterization+of+overexpression+or+deletion+of+the+Escherichia+coli+crcA%2C+cspE+and+crcB+genes&rft.au=Sand%2C+O%3BGingras%2C+M%3BBeck%2C+N%3BHall%2C+C%3BTrun%2C+N&rft.aulast=Sand&rft.aufirst=O&rft.date=2003-08-01&rft.volume=149&rft.issue=8&rft.spage=2107&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&rft_id=info:doi/10.1099%2Fmic.0.26363-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Overexpression; Deletion mutant; Genetic analysis; Stress; Plasmids; Supercoiling; DNA topoisomerase; DNA topoisomerase IV DO - http://dx.doi.org/10.1099/mic.0.26363-0 ER - TY - JOUR T1 - Novel insights into muscarinic acetylcholine receptor function using gene targeting technology AN - 18958251; 5742012 AB - Muscarinic acetylcholine receptors (mAChRs) modulate the activity of an extraordinarily large number of physiological functions. Individual members of the mAChR family (M sub(1)-M sub(5)) are expressed in a complex, overlapping fashion in most tissues and cell types. However, the identification of the precise physiological roles of individual mAChR subtypes remains a challenging task because, with the exception of a few snake toxins, mAChR ligands that can activate or inhibit specific mAChR subtypes with a high degree of selectivity are not yet available. Knowledge of the specific roles of mAChR subtypes is of considerable interest for the development of novel, clinically useful mAChR ligands. In this article, recent studies of mutant mouse strains developed, using gene targeting techniques, to be deficient in one of the three G sub(q)-coupled mAChR subtypes (M sub(1), M sub(3) and M sub(5)) are discussed. These investigations have led to many important new insights into the physiological roles of these receptor subtypes. JF - Trends in Pharmacological Sciences AU - Wess, J AD - Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, DHHS, Bethesda, MD 20892, USA, jwess@helix.nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 414 EP - 420 VL - 24 IS - 8 SN - 0165-6147, 0165-6147 KW - mice KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Gene targeting KW - Acetylcholine receptors (muscarinic M3) KW - Receptor mechanisms KW - Structure-function relationships KW - Acetylcholine receptors (muscarinic M1) KW - Reviews KW - Acetylcholine receptors (muscarinic M5) KW - Mutants KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - N3 11091:Vertebrate Nervous Systems: General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18958251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Pharmacological+Sciences&rft.atitle=Novel+insights+into+muscarinic+acetylcholine+receptor+function+using+gene+targeting+technology&rft.au=Wess%2C+J&rft.aulast=Wess&rft.aufirst=J&rft.date=2003-08-01&rft.volume=24&rft.issue=8&rft.spage=414&rft.isbn=&rft.btitle=&rft.title=Trends+in+Pharmacological+Sciences&rft.issn=01656147&rft_id=info:doi/10.1016%2FS0165-6147%2803%2900195-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Acetylcholine receptors (muscarinic M1); Acetylcholine receptors (muscarinic M3); Acetylcholine receptors (muscarinic M5); Structure-function relationships; Receptor mechanisms; Gene targeting; Mutants DO - http://dx.doi.org/10.1016/S0165-6147(03)00195-0 ER - TY - JOUR T1 - Tissue Molecular Anatomy Project (TMAP): An expression database for comparative cancer proteomics AN - 18948373; 5736956 AB - By mining publicly accessible databases, we have developed a collection of tissue-specific predictive protein expression maps as a function of cancer histological state. Data analysis is applied to the differential expression of gene products in pooled libraries from the normal to the altered state(s). We wish to report the initial results of our survey across different tissues and explore the extent to which this comparative approach may help uncover panels of potential biomarkers of tumorigenesis which would warrant further examination in the laboratory. JF - Proteomics AU - Medjahed, D AU - Luke, B T AU - Tontesh, T S AU - Smythers, G W AU - Munroe, D J AU - Lemkin, P F AD - National Cancer Institute at Frederick, P.O. Box B, Frederick, MD 21702-1201, USA, medjahed@ncifcrf.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 1445 EP - 1453 VL - 3 IS - 8 SN - 1615-9853, 1615-9853 KW - proteomics KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Databases KW - Data processing KW - Protein biosynthesis KW - Tumorigenesis KW - Cancer KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18948373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteomics&rft.atitle=Tissue+Molecular+Anatomy+Project+%28TMAP%29%3A+An+expression+database+for+comparative+cancer+proteomics&rft.au=Medjahed%2C+D%3BLuke%2C+B+T%3BTontesh%2C+T+S%3BSmythers%2C+G+W%3BMunroe%2C+D+J%3BLemkin%2C+P+F&rft.aulast=Medjahed&rft.aufirst=D&rft.date=2003-08-01&rft.volume=3&rft.issue=8&rft.spage=1445&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&rft_id=info:doi/10.1002%2Fpmic.200300488 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Protein biosynthesis; Tumorigenesis; Cancer; Databases; Data processing DO - http://dx.doi.org/10.1002/pmic.200300488 ER - TY - JOUR T1 - Manganese superoxide dismutase (MnSOD) polymorphism, alpha -tocopherol supplementation and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Finland) AN - 18884083; 5742400 AB - Objective: Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that plays a key role in protecting the cell from oxidative damage. A polymorphism in the mitochondrial targeting sequence (a valine to alanine substitution), thought to alter transport of the enzyme into mitochondria, has been associated with increased risk for breast cancer with a more pronounced association among women with low intake of dietary antioxidants. We examined the role of MnSOD in the development of prostate cancer in a large, randomized cancer prevention trial of male smokers, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We hypothesized that MnSOD may be associated with prostate cancer and that long-term antioxidant supplementation ( alpha -tocopherol 50 mg/day for five to eight years) could modify the effect on risk. Methods: Logistic regression was used to estimate these associations among 197 cases and 190 controls genotyped and matched for age, intervention group, and clinic. Results: Men homozygous for the MnSOD ala allele had a 70% increase in risk over men homozygous for the val allele (odds ratio, OR = 1.72, 95% confidence interval, CI = 0.96-3.08, p = 0.07). Supplementation with alpha -tocopherol had no impact on the MnSOD-prostate cancer association. Although there was no difference in the association with disease stage, men homozygous for MnSOD ala (compared to MnSOD val/val or val/ala) showed a three-fold risk increase for high-grade tumors (OR = 2.72, 95% CI: 1.15-6.40, p = 0.02). Conclusion: These data suggest an effect of the MnSOD ala/ala genotype on the development of prostate cancer. Our observation of a stronger association with high-grade tumors may have prognostic implications that should also be pursued. JF - Cancer Causes & Control AU - Woodson, K AU - Tangrea, JA AU - Lehman, T A AU - Modali, R AU - Taylor, K M AU - Snyder, K AU - Taylor, PR AU - Virtamo, J AU - Albanes, D AD - Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, 6116 Executive Boulevard MSC 8314, Bethesda, MD 20892-7058, USA, kw114v@nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 513 EP - 518 VL - 14 IS - 6 SN - 0957-5243, 0957-5243 KW - alpha -Tocopherol KW - man KW - Toxicology Abstracts KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18884083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Manganese+superoxide+dismutase+%28MnSOD%29+polymorphism%2C+alpha+-tocopherol+supplementation+and+prostate+cancer+risk+in+the+Alpha-Tocopherol%2C+Beta-Carotene+Cancer+Prevention+Study+%28Finland%29&rft.au=Woodson%2C+K%3BTangrea%2C+JA%3BLehman%2C+T+A%3BModali%2C+R%3BTaylor%2C+K+M%3BSnyder%2C+K%3BTaylor%2C+PR%3BVirtamo%2C+J%3BAlbanes%2C+D&rft.aulast=Woodson&rft.aufirst=K&rft.date=2003-08-01&rft.volume=14&rft.issue=6&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Sugarcane Farming, Occupational Solvent Exposures, and the Risk of Oral Cancer in Puerto Rico AN - 18880980; 5738142 AB - The work history information from a population-based case-control study conducted in Puerto Rico was analyzed using a job exposure matrix to investigate the relationship between occupational exposures and cancers of the oral cavity or pharynx. After adjustment for age, alcohol, smoking, and residence in a logistic model, the risk for cancer of the oral cavity, but not the pharynx, was significantly elevated among farm workers in the sugarcane industry (OR = 4.4, 95% CI = 1.4-13.6). An exposure-response trend was seen for cumulative exposure to solvents, with an OR = 3.2 (95% CI = 0.8-12.6) in the highest exposure category. The overall contribution to the risk of cancer of the oral cavity or pharynx associated with occupational exposures in Puerto Rico appears to be small, however, the elevated risks were seen among sugarcane farmers and subjects with high cumulative exposure to solvents. JF - Journal of Occupational and Environmental Medicine AU - Coble, J B AU - Brown, L M AU - Hayes, R B AU - Huang, Wen-Yi AU - Winn, D M AU - Gridley, G AU - Bravo-Otero, E AU - Fraumeni, JF Jr AD - DCEG, NCI, NIH, DHHS, 6120 Executive Boulevard, Room 8110, MSC 7240, Bethesda, MD 20892-7240, USA, jcoble@mail.nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 869 EP - 874 VL - 45 IS - 8 SN - 1076-2752, 1076-2752 KW - farming KW - man KW - oral cavity KW - pharynx KW - Toxicology Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - R2 23080:Industrial and labor 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/18880980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Occupational+and+Environmental+Medicine&rft.atitle=Sugarcane+Farming%2C+Occupational+Solvent+Exposures%2C+and+the+Risk+of+Oral+Cancer+in+Puerto+Rico&rft.au=Coble%2C+J+B%3BBrown%2C+L+M%3BHayes%2C+R+B%3BHuang%2C+Wen-Yi%3BWinn%2C+D+M%3BGridley%2C+G%3BBravo-Otero%2C+E%3BFraumeni%2C+JF+Jr&rft.aulast=Coble&rft.aufirst=J&rft.date=2003-08-01&rft.volume=45&rft.issue=8&rft.spage=869&rft.isbn=&rft.btitle=&rft.title=Journal+of+Occupational+and+Environmental+Medicine&rft.issn=10762752&rft_id=info:doi/10.1097%2F01.jom.0000083034.56116.0f LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1097/01.jom.0000083034.56116.0f ER - TY - JOUR T1 - Transfection-independent production of alphavirus replicon particles based on poxvirus expression vectors AN - 18874292; 5718719 AB - This report describes a transfection-independent system for packaging alphavirus replicon vectors using modified vaccinia virus Ankara (MVA) vectors to express all of the RNA components necessary for the production of Venezuelan equine encephalitis (VEE) virus replicon particles (VRP). Infection of mammalian cells with these recombinant MVA vectors resulted in robust expression of VEE structural genes, replication of the alphavirus vector and high titers of VRP. In addition, VRP packaging was achieved in a cell type (fetal rhesus lung) that has been approved for the manufacturing of vaccines destined for human use. JF - Nature Biotechnology AU - Vasilakis, N AU - Falvey, D AU - Gangolli, S S AU - Coleman, J AU - Kowalski, J AU - Udem, SA AU - Zamb, T J AU - Kovacs, G R AD - Office of Biodefense Research Affairs, National Institute of Allergy and Infectious Diseases, National Institutes of Heath, Bethesda, MD 20892, USA, gkovacs@niaid.nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 932 EP - 935 VL - 21 IS - 8 SN - 1087-0156, 1087-0156 KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33365:Vaccines (other) 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/18874292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Transfection-independent+production+of+alphavirus+replicon+particles+based+on+poxvirus+expression+vectors&rft.au=Vasilakis%2C+N%3BFalvey%2C+D%3BGangolli%2C+S+S%3BColeman%2C+J%3BKowalski%2C+J%3BUdem%2C+SA%3BZamb%2C+T+J%3BKovacs%2C+G+R&rft.aulast=Vasilakis&rft.aufirst=N&rft.date=2003-08-01&rft.volume=21&rft.issue=8&rft.spage=932&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2Fnbt845 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/nbt845 ER - TY - JOUR T1 - Environmental Threats to Children's Health in Southeast Asia and the Western Pacific AN - 18866790; 5711828 AB - The Southeast Asia and Western Pacific regions contain half of the world's children and are among the most rapidly industrializing regions of the globe. Environmental threats to children's health are widespread and are multiplying as nations in the area undergo industrial development and pass through the epidemiologic transition. These environmental hazards range from traditional threats such as bacterial contamination of drinking water and wood smoke in poorly ventilated dwellings to more recently introduced chemical threats such as asbestos construction materials; arsenic in groundwater; methyl isocyanate in Bhopal, India; untreated manufacturing wastes released to landfills; chlorinated hydrocarbon and organophosphorous pesticides; and atmospheric lead emissions from the combustion of leaded gasoline. To address these problems, pediatricians, environmental health scientists, and public health workers throughout Southeast Asia and the Western Pacific have begun to build local and national research and prevention programs in children's environmental health. Successes have been achieved as a result of these efforts: A cost-effective system for producing safe drinking water at the village level has been devised in India; many nations have launched aggressive antismoking campaigns; and Thailand, the Philippines, India, and Pakistan have all begun to reduce their use of lead in gasoline, with resultant declines in children's blood lead levels. The International Conference on Environmental Threats to the Health of Children, held in Bangkok, Thailand, in March 2002, brought together more than 300 representatives from 35 countries and organizations to increase awareness on environmental health hazards affecting children in these regions and throughout the world. The conference, a direct result of the Environmental Threats to the Health of Children meeting held in Manila in April 2000, provided participants with the latest scientific data on children's vulnerability to environmental hazards and models for future policy and public health discussions on ways to improve children's health. The Bangkok Statement, a pledge resulting from the conference proceedings, is an important first step in creating a global alliance committed to developing active and innovative national and international networks to promote and protect children's environmental health. JF - Environmental Health Perspectives AU - Suk, WA AU - Ruchirawat, K M AU - Balakrishnan, K AU - Berger, M AU - Carpenter, D AU - Damstra, T AU - De Garbino, JP AU - Koh, D AU - Landrigan, P J AU - Makalinao, I AU - Sly, P D AU - Xu, Y AU - Zheng, B S AD - NIEHS, 79 T.W. Alexander Dr., 4401 Bldg, Mail Drop EC-27, Research Triangle Park, NC 27709, USA, suk@niehs.nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 1340 EP - 1347 PB - NIH, Government Printing Office VL - 111 IS - 10 SN - 0091-6765, 0091-6765 KW - Health & Safety Science Abstracts; Pollution Abstracts; Risk Abstracts KW - R2 23060:Medical and environmental health KW - H 12000:Epidemiology and Public Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18866790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Environmental+Threats+to+Children%27s+Health+in+Southeast+Asia+and+the+Western+Pacific&rft.au=Suk%2C+WA%3BRuchirawat%2C+K+M%3BBalakrishnan%2C+K%3BBerger%2C+M%3BCarpenter%2C+D%3BDamstra%2C+T%3BDe+Garbino%2C+JP%3BKoh%2C+D%3BLandrigan%2C+P+J%3BMakalinao%2C+I%3BSly%2C+P+D%3BXu%2C+Y%3BZheng%2C+B+S&rft.aulast=Suk&rft.aufirst=WA&rft.date=2003-08-01&rft.volume=111&rft.issue=10&rft.spage=1340&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Fehp.6059 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1289/ehp.6059 ER - TY - JOUR T1 - Amyotrophic Lateral Sclerosis, Lead, and Genetic Susceptibility: Polymorphisms in the delta -Aminolevulinic Acid Dehydratase and Vitamin D Receptor Genes AN - 18826040; 5711827 AB - Previous studies have suggested that lead exposure may be associated with increased risk of amyotrophic lateral sclerosis (ALS). Polymorphisms in the genes for delta -aminolevulinic acid dehydratase (ALAD) and the vitamin D receptor (VDR) may affect susceptibility to lead exposure. We used data from a case-control study conducted in New England from 1993 to 1996 to evaluate the relationship of ALS to polymorphisms in ALAD and VDR and the effect of these polymorphisms on the association of ALS with lead exposure. The ALAD 2 allele (177G to C; K59N) was associated with decreased lead levels in both patella and tibia, although not in blood, and with an imprecise increase in ALS risk [odds ratio (OR) = 1.9; 95% confidence interval (95% CI), 0.60-6.31. We found a previously unreported polymorphism in ALAD at an Msp1 site in intron 2 (IVS2+299G>A) that was associated with decreased bone lead levels and with an imprecise decrease in ALS risk (OR = 0.35; 95% CI, 0.10-1.2). The VDR B allele was not associated with lead levels or ALS risk. Our ability to observe effects of genotype on associations of ALS with occupational exposure to lead or with blood or bone lead levels was limited. These findings suggest that genetic susceptibility conferred by polymorphisms in ALAD may affect ALS risk, possibly through a mechanism related to internal lead exposure. JF - Environmental Health Perspectives AU - Kamel, F AU - Umbach, D M AU - Lehman, T A AU - Park, L P AU - Munsat, T L AU - Shefner, J M AU - Sandler, D P AU - Hu, H AU - Taylor, JA AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Box 12233, MD A3-05, Research Triangle Park, NC 27709, USA, kamel@niehs.nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 1335 EP - 1339 PB - NIH, Government Printing Office VL - 111 IS - 10 SN - 0091-6765, 0091-6765 KW - man KW - Toxicology Abstracts KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18826040?accountid=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=Amyotrophic+Lateral+Sclerosis%2C+Lead%2C+and+Genetic+Susceptibility%3A+Polymorphisms+in+the+delta+-Aminolevulinic+Acid+Dehydratase+and+Vitamin+D+Receptor+Genes&rft.au=Kamel%2C+F%3BUmbach%2C+D+M%3BLehman%2C+T+A%3BPark%2C+L+P%3BMunsat%2C+T+L%3BShefner%2C+J+M%3BSandler%2C+D+P%3BHu%2C+H%3BTaylor%2C+JA&rft.aulast=Kamel&rft.aufirst=F&rft.date=2003-08-01&rft.volume=111&rft.issue=10&rft.spage=1335&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Fehp.6109 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1289/ehp.6109 ER - TY - JOUR T1 - Generation of Tumor-Infiltrating Lymphocyte Cultures for Use in Adoptive Transfer Therapy for Melanoma Patients AN - 18825551; 5719335 AB - The generation of T lymphocytes with specific reactivity against tumor antigens is a prerequisite for effective adoptive transfer therapies. Melanoma-specific lymphocyte cultures can be established from tumor infiltrating lymphocytes (TILs) by in vitro culture in high levels of IL-2. We have optimized methods for generating melanoma-reactive TIL cultures from small resected tumor specimens. We report a retrospective analysis of 860 attempted TIL cultures from 90 sequential melanoma biopsy specimens from 62 HLA-A2 super(+) patients. Multiple independent TIL derived from a single tumor often exhibited substantial functional and phenotypic variation. Tumor specific activity was detected in TIL from 29 (81%) of 36 patients screened. TIL cultures selected for high activity were generally capable of large numerical expansion using a single round of a rapid expansion protocol. Limited clonal T-cell populations in an oligoclonal TIL culture could confer specific tumor recognition in these highly selected, highly expanded TIL cultures. These methods were efficient at generating TILs suitable for adoptive transfer therapy. JF - Journal of Immunotherapy AU - Dudley, ME AU - Wunderlich, J R AU - Shelton, TE AU - Even, J AU - Rosenberg, SA AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B-08, 10 Center Drive, Bethesda, MD 20892-1502, USA, mark_dudley@nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 332 EP - 342 VL - 26 IS - 4 SN - 1067-5582, 1067-5582 KW - A2 dterminant KW - histocompatibility antigen HLA KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts; Immunology Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - F 06818:Cancer immunotherapy KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18825551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy&rft.atitle=Generation+of+Tumor-Infiltrating+Lymphocyte+Cultures+for+Use+in+Adoptive+Transfer+Therapy+for+Melanoma+Patients&rft.au=Dudley%2C+ME%3BWunderlich%2C+J+R%3BShelton%2C+TE%3BEven%2C+J%3BRosenberg%2C+SA&rft.aulast=Dudley&rft.aufirst=ME&rft.date=2003-08-01&rft.volume=26&rft.issue=4&rft.spage=332&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy&rft.issn=10675582&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - HIV risk behaviour among psychiatric inpatients: results from a hospital-wide screening study in southern India AN - 18823466; 5710906 AB - The study was carried out to investigate the prevalence and correlates of sexual risk behaviour among psychiatric inpatients in India. Consecutive inpatients (n=618) were assessed using a structured interview and standardized measures. Women were more likely to be sexually active (50%) than men (36%), but equally likely (6% vs 5%) to engage in risky behaviour. Common risk behaviours included having a risky partner, having multiple partners, and exchanging money for sex. Being sexually active was associated with younger age, being married, being diagnosed with a disorder other than schizophrenia, and a history of drug use problems. Engaging in risky sexual behaviour was associated with being male, using tobacco and screening positive for either drug use or alcohol problems. Screening psychiatric patients for HIV risk behaviour can identify those who may benefit from risk reduction programmes. JF - International Journal of STD & AIDS AU - Chandra, P S AU - Carey, M P AU - Carey, K B AU - Prasada Rao, PSDV AU - Jairam, K R AU - Thomas, T AD - Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India, prabhchandra@rediffmail.com Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 532 EP - 538 VL - 14 IS - 8 SN - 0956-4624, 0956-4624 KW - HIV KW - man KW - mental disorders KW - sexual behavior KW - Risk Abstracts; Virology & AIDS Abstracts 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/18823466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+STD+%26+AIDS&rft.atitle=HIV+risk+behaviour+among+psychiatric+inpatients%3A+results+from+a+hospital-wide+screening+study+in+southern+India&rft.au=Chandra%2C+P+S%3BCarey%2C+M+P%3BCarey%2C+K+B%3BPrasada+Rao%2C+PSDV%3BJairam%2C+K+R%3BThomas%2C+T&rft.aulast=Chandra&rft.aufirst=P&rft.date=2003-08-01&rft.volume=14&rft.issue=8&rft.spage=532&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+STD+%26+AIDS&rft.issn=09564624&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 - Ethnic Differences Among Correlates of Physical Activity in Women AN - 18811803; 5689149 AB - This study investigated differences between two ethnic minority groups on five hypothesized correlates of physical activity (beliefs about the value of physical activity, normative modeling, perceived barriers, outcome expectations, and self-efficacy). A cross-sectional sample consisting of 246 African American and Hispanic women 40 to 70 years of age was used. Multivariate analysis of covariance including interactions with education and income was used. A three-way interaction (ethnicity by education by income) was significant for perceived barriers. In addition, a two-way interaction (education by income) was significant for normative modeling. Ethnic differences by education and income were associated with some correlates of physical activity; therefore, it is important to consider this diversity when designing physical-activity interventions for minority women. JF - American Journal of Health Promotion AU - Masse, L C AU - Anderson, C B AD - National Cancer Institute, Division of Cancer Control and Population Sciences, Behavioral Research Program, Health Promotion Research Branch, 6130 Executive Blvd, EPN 4076 MSC 7335, Bethesda, MD 20892-7335, USA Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 357 EP - 360 VL - 17 IS - 6 SN - 0890-1171, 0890-1171 KW - Physical Education Index KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18811803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Health+Promotion&rft.atitle=Ethnic+Differences+Among+Correlates+of+Physical+Activity+in+Women&rft.au=Masse%2C+L+C%3BAnderson%2C+C+B&rft.aulast=Masse&rft.aufirst=L&rft.date=2003-08-01&rft.volume=17&rft.issue=6&rft.spage=357&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Health+Promotion&rft.issn=08901171&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Autoinducer 2 Production by Streptococcus gordonii DL1 and the Biofilm Phenotype of a luxS Mutant Are Influenced by Nutritional Conditions AN - 18811298; 5689851 AB - The luxS gene, present in many bacterial genera, encodes the autoinducer 2 (AI-2) synthase. AI-2 has been implicated in bacterial signaling, and this study investigated its role in biofilm formation by Streptococcus gordonii, an organism that colonizes human tooth enamel within the first few hours after professional cleaning. Northern blotting and primer extension analyses revealed that S. gordonii luxS is monocistronic. AI-2 production was dependent on nutritional conditions, and maximum AI-2 induction was detected when S. gordonii was grown in the presence of serum and carbonate. In planktonic cultures, AI-2 production rose sharply during the transition from exponential to stationary phase, and the AI-2 concentration peaked approximately 4 h into stationary phase. An S. gordonii luxS mutant that did not produce AI-2 was constructed by homologous recombination. Complementation of the mutant by insertion of an intact luxS gene into the chromosome in tandem with the disrupted gene restored AI-2 production to a level similar to that of the wild-type strain. In planktonic culture, no growth differences were observed between the mutant and wild-type strains when five different media were used. However, when grown for 4 h as biofilms in 25% human saliva under flow, the luxS mutant formed tall microcolonies that differed from those formed by the wild-type and complemented mutant strains. Biofilms of the luxS mutant exhibited finger-like projections of cells that extended into the flow cell lumen. Thus, the inability to produce AI-2 is associated with altered microcolony architecture within S. gordonii biofilms formed in saliva during a time frame consistent with initial colonization of freshly cleaned enamel surfaces. JF - Journal of Bacteriology AU - Blehert, D S AU - Palmer, RJ Jr AU - Xavier, J B AU - Almeida, J S AU - Kolenbrander, P E AD - Building 30, Room 310, 30 Convent Dr. MSC 4350, National Institutes of Health/NIDCR, Bethesda, MD 20892-4350, pkolenbrander@dir.nidcr.nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 4851 EP - 4860 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 185 IS - 16 SN - 0021-9193, 0021-9193 KW - Autoinducer 2 synthase KW - carbonic acid KW - luxS gene KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18811298?accountid=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=Autoinducer+2+Production+by+Streptococcus+gordonii+DL1+and+the+Biofilm+Phenotype+of+a+luxS+Mutant+Are+Influenced+by+Nutritional+Conditions&rft.au=Blehert%2C+D+S%3BPalmer%2C+RJ+Jr%3BXavier%2C+J+B%3BAlmeida%2C+J+S%3BKolenbrander%2C+P+E&rft.aulast=Blehert&rft.aufirst=D&rft.date=2003-08-01&rft.volume=185&rft.issue=16&rft.spage=4851&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.185.16.4851-4860.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.185.16.4851-4860.2003 ER - TY - JOUR T1 - Correlation of Acetate Catabolism and Growth Yield in Staphylococcus aureus: Implications for Host-Pathogen Interactions AN - 18805315; 5675873 AB - Recently, we reported that the prototypical Staphylococcus aureus strain RN6390 (a derivative of NCTC 8325) had significantly reduced aconitase activity relative to a diverse group of S. aureus isolates, leading to the hypothesis that strain RN6390 has impaired tricarboxylic acid (TCA) cycle-mediated acetate catabolism. Analysis of the culture supernatant from RN6390 confirmed that acetate was incompletely catabolized, suggesting that the ability to catabolize acetate can be lost by S. aureus. To test this hypothesis, we examined the carbon catabolism of the S. aureus strains whose genome sequences are publicly available. All strains catabolized glucose and excreted acetate into the culture medium. However, strains NCTC 8325 and N315 failed to catabolize acetate during the postexponential growth phase, resulting in significantly lower growth yields relative to strains that catabolized acetate. Strains NCTC 8325 and RN6390 contained an 11-bp deletion in rsbU, the gene encoding a positive regulator of the alternative sigma factor capital sigma super(B) encoded by sigB. An isogenic derivative strain of RN6390 containing the wild-type rsbU gene had significantly increased acetate catabolism, demonstrating that capital sigma super(B) is required for acetate catabolism. Taken together, the data suggest that naturally occurring mutations can alter the ability of S. aureus to catabolize acetate, a surprising discovery, as TCA cycle function has been demonstrated to be involved in the virulence, survival, and persistence of several pathogenic organisms. Additionally, these mutations decrease the fitness of S. aureus by reducing the number of progeny placed into subsequent generations, suggesting that in certain situations a decreased growth yield is advantageous. JF - Infection and Immunity AU - Somerville, G A AU - Saied-Salim, B AU - Wickman, J M AU - Raffel, S J AU - Kreiswirth, B N AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, gsomerville@niaid.nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 4724 EP - 4732 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 71 IS - 8 SN - 0019-9567, 0019-9567 KW - sigma B Factor KW - sigma B factor KW - rsbU gene KW - sigB gene KW - tricarboxylic acid KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18805315?accountid=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=Correlation+of+Acetate+Catabolism+and+Growth+Yield+in+Staphylococcus+aureus%3A+Implications+for+Host-Pathogen+Interactions&rft.au=Somerville%2C+G+A%3BSaied-Salim%2C+B%3BWickman%2C+J+M%3BRaffel%2C+S+J%3BKreiswirth%2C+B+N%3BMusser%2C+J+M&rft.aulast=Somerville&rft.aufirst=G&rft.date=2003-08-01&rft.volume=71&rft.issue=8&rft.spage=4724&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.71.8.4724-4732.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.71.8.4724-4732.2003 ER - TY - JOUR T1 - In Vivo Induction of Integrated HIV-1 Expression by Mycobacteria Is Critically Dependent on Toll-Like Receptor 2 AN - 18799511; 5668046 AB - Mycobacterial infection has been implicated as a possible factor in AIDS progression in populations where HIV-1 and Mycobacterium tuberculosis are coendemic. In support of this concept, we have previously shown that HIV-1- transgenic (Tg) mice infected with mycobacteria display enhanced viral gene and protein expression. In this study, we demonstrate that the induction of HIV-1 observed in this model is dependent on Toll-like receptor 2 (TLR2), a pattern recognition receptor known to be involved in mycobacteria-host interaction. Spleen cells from HIV-1-Tg mice deficient in TLR2 (Tg/TLR2 super(-/-)) were found to be completely defective in p24 production induced in response to live M. tuberculosis or Mycobacterium avium as well as certain mycobacterial products. Importantly, following in vivo mycobacterial infection, Tg/TLR2 super(-/-) mice failed to display the enhanced HIV-1 gag/env mRNA and p24 protein synthesis exhibited by wild-type Tg animals. Together, these results argue that TLR2 plays a crucial role in the activation of HIV-1 expression by mycobacterial coinfections. JF - Journal of Immunology AU - Bafica, A AU - Scanga, CA AU - Schito, M L AU - Hieny, S AU - Sher, A AD - Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases and Chemical Immunology Section, Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 Y1 - 2003/08/01/ PY - 2003 DA - 2003 Aug 01 SP - 1123 EP - 1127 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 171 IS - 3 SN - 0022-1767, 0022-1767 KW - HIV-1 KW - TLR2 protein KW - Toll-like receptors KW - mice KW - p24 protein KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Immunology Abstracts KW - J 02833:Immune response and immune mechanisms KW - V 22003:AIDS: Immunological aspects KW - F 06800:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18799511?accountid=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+Immunology&rft.atitle=In+Vivo+Induction+of+Integrated+HIV-1+Expression+by+Mycobacteria+Is+Critically+Dependent+on+Toll-Like+Receptor+2&rft.au=Bafica%2C+A%3BScanga%2C+CA%3BSchito%2C+M+L%3BHieny%2C+S%3BSher%2C+A&rft.aulast=Bafica&rft.aufirst=A&rft.date=2003-08-01&rft.volume=171&rft.issue=3&rft.spage=1123&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 ER - TY - JOUR T1 - DNA Immunization with the Cysteine-Rich Interdomain Region 1 of the Plasmodium falciparum Variant Antigen Elicits Limited Cross-Reactive Antibody Responses AN - 18796917; 5675759 AB - The variant surface antigens of Plasmodium falciparum are an important component of naturally acquired immunity and an important vaccine target. However, these proteins appear to elicit primarily variant-specific antibodies. We tested if naked DNA immunization can elicit more cross-reactive antibody responses and allow simultaneous immunization with several variant constructs. Mice immunized with plasmid DNA expressing variant cysteine-rich interdomain region 1 (CIDR1) domains of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) developed antibodies that were reactive to the corresponding PfEMP1s as measured by an enzyme-linked immunosorbent assay, flow cytometry, and agglutination of parasitized erythrocytes (PEs). We observed some cross-reactive immune responses; for example, sera from mice immunized with one domain agglutinated PEs of various lines and recognized heterologous domains expressed on the surface of Chinese hamster ovary (CHO) cells. We found no significant antigenic competition when animals were immunized with a mixture of plasmids or immunized sequentially with individual constructs. Moreover, mixed or sequential immunizations resulted in greater cross-reactive agglutination responses than immunization with a single domain. Recombinant protein (Sc y179) immunization after priming with DNA (prime-boost regimen) increased antibody titers to the homologous domain substantially but seemed to diminish the cross-reactive responses somewhat. The titer of agglutinating antibodies was previously shown to correlate with protection. Surprisingly, the agglutination titers of sera from DNA immunization were high, similar to those of pooled human hyperimmune sera. These sera also appeared to give limited low-titer variant transcending agglutination. Thus, DNA immunization appears to be a very useful tool for developing variant antigen vaccines. JF - Infection and Immunity AU - Baruch, DI AU - Gamain, B AU - Miller, L H AD - Laboratory of Malaria and Vector Research, NIAID, NIH, Bldg. 4, Room B1-37, 4 Center Drive MSC 0425, Bethesda, MD 20892-0425, dbaruch@niaid.nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 4536 EP - 4543 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 71 IS - 8 SN - 0019-9567, 0019-9567 KW - EMP1 protein KW - PfEMP1 protein KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biochemistry Abstracts 2: Nucleic Acids KW - K 03086:Immunology & vaccination KW - F 06807:Active immunization KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews KW - N 14800:Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18796917?accountid=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=Infection+and+Immunity&rft.atitle=DNA+Immunization+with+the+Cysteine-Rich+Interdomain+Region+1+of+the+Plasmodium+falciparum+Variant+Antigen+Elicits+Limited+Cross-Reactive+Antibody+Responses&rft.au=Baruch%2C+DI%3BGamain%2C+B%3BMiller%2C+L+H&rft.aulast=Baruch&rft.aufirst=DI&rft.date=2003-08-01&rft.volume=71&rft.issue=8&rft.spage=4536&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.71.8.4536-4543.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.71.8.4536-4543.2003 ER - TY - JOUR T1 - Objective, Real-Time, Intraoperative Assessment of Renal Perfusion Using Infrared Imaging AN - 17879932; 5767751 AB - Allograft ischemia induces delayed graft function and is correlated with increasing rates of rejection. There is not currently a way to objectively measure the effects of ischemia in real-time, nor to relate therapies combating reperfusion injury with their intended effects. An infrared (IR) method utilizing a focal plane array detector camera was developed for real-time intraoperative IR imaging of renal allografts, and evaluated in a pilot trial to quantify perfusion in recipients of live (n = 8) and cadaveric donor (n = 5) allografts. Digital images were taken for 3-8 min postreperfusion. Image data were compared to ischemic time and allograft function to assess potential clinical relevance. Cold ischemic time ranged from 0.5 to 29 h and was bimodally distributed between living and cadaveric donors. Renal rewarming time (RT) as determined by IR imaging correlated with cold ischemic time (p < 0.001, R super(2) = 0.81), and predicted the subsequent return of renal function with RT negatively correlated to the regression slopes of creatinine (p = 0.02, R super(2) = 0.38) and BUN (p = 0.07, R super(2) = 0.26). Intraoperative IR imaging noninvasively provides clinically relevant real-time whole kidney assessment of reperfusion. This technology may aide in the objective assessment of therapies designed to limit reperfusion injury, and allow for quantitative assessment of allograft ischemic damage. JF - American Journal of Transplantation AU - Gorbach, A AU - Simonton, D AU - Hale, DA AU - Swanson, John, S AU - Kirk, AD AD - Transplantation and Autoimmunity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA, allank@intra.niddk.nih.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 988 EP - 993 VL - 3 IS - 8 SN - 1600-6135, 1600-6135 KW - man KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Bioengineering Abstracts KW - Data processing KW - Perfusion KW - Graft rejection KW - Kidney transplantation KW - Image processing KW - Ischemia KW - Clinical trials KW - imaging KW - Reperfusion KW - Creatinine KW - Renal function KW - I.R. spectroscopy KW - Allografts KW - Cameras KW - Cadavers KW - F 06832:Kidney KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17879932?accountid=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=American+Journal+of+Transplantation&rft.atitle=Objective%2C+Real-Time%2C+Intraoperative+Assessment+of+Renal+Perfusion+Using+Infrared+Imaging&rft.au=Gorbach%2C+A%3BSimonton%2C+D%3BHale%2C+DA%3BSwanson%2C+John%2C+S%3BKirk%2C+AD&rft.aulast=Gorbach&rft.aufirst=A&rft.date=2003-08-01&rft.volume=3&rft.issue=8&rft.spage=988&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Transplantation&rft.issn=16006135&rft_id=info:doi/10.1034%2Fj.1600-6143.2003.00158.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Ischemia; Reperfusion; imaging; Perfusion; Creatinine; Cameras; Clinical trials; Kidney transplantation; Renal function; Graft rejection; Allografts; Cadavers; Image processing; I.R. spectroscopy; Data processing DO - http://dx.doi.org/10.1034/j.1600-6143.2003.00158.x ER - TY - JOUR T1 - Profiling of Secreted Proteins from Human Ovarian Cancer Cell Lines by Surface-Enhanced Laser Desorption Ionization Time-of-Flight Mass Spectrometry AN - 17843868; 5738097 AB - Surface-enhanced laser desorption ionization (SELDI) time-of-flight mass spectrometry (TOF MS) was used to profile six human ovarian cancer cell lines. Non-confluent cell cultures were exchanged into serum free medium and allowed to grow for either 24 or 48 hours, at which time the medium was collected and analyzed using a Ciphergen SELDI-TOF MS and a QSTAR Pulsar QqTOF mass spectrometer fitted with a SELDI source. The spectra showed the presence of several low molecular weight species, as well as differences and similarities in the proteins detected in the media of the six ovarian tumor cell lines. The same species were detected at 24 and 48 hours and reproducible changes in their relative abundances were observed. JF - Journal of Liquid Chromatography & Related Technologies AU - Prieto, D AU - Conrads, T P AU - Scudiero, DA AU - Veenstra, T D AU - Issaq, HJ AD - Analytical Chemistry Laboratory, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD 21702, USA, issaqh@mail.ncifcrf.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 2315 EP - 2328 VL - 26 IS - 14 SN - 1082-6076, 1082-6076 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Ovarian cancer KW - Tumor cell lines KW - Desorption KW - Liquid chromatography KW - Cell culture KW - Lasers KW - proteomics KW - Mass spectroscopy KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17843868?accountid=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+Liquid+Chromatography+%26+Related+Technologies&rft.atitle=Profiling+of+Secreted+Proteins+from+Human+Ovarian+Cancer+Cell+Lines+by+Surface-Enhanced+Laser+Desorption+Ionization+Time-of-Flight+Mass+Spectrometry&rft.au=Prieto%2C+D%3BConrads%2C+T+P%3BScudiero%2C+DA%3BVeenstra%2C+T+D%3BIssaq%2C+HJ&rft.aulast=Prieto&rft.aufirst=D&rft.date=2003-08-01&rft.volume=26&rft.issue=14&rft.spage=2315&rft.isbn=&rft.btitle=&rft.title=Journal+of+Liquid+Chromatography+%26+Related+Technologies&rft.issn=10826076&rft_id=info:doi/10.1081%2FJLC-120023249 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Proteomics. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tumor cell lines; Mass spectroscopy; Lasers; Desorption; Ovarian cancer; Cell culture; proteomics; Liquid chromatography DO - http://dx.doi.org/10.1081/JLC-120023249 ER - TY - JOUR T1 - Effect of Experimental Parameters on the HPLC Separation of Peptides and Proteins AN - 17842285; 5738094 AB - This manuscript examines the effects of different experimental parameters on resolution, peak symmetry, peak width, and selectivity (peak elution order) of peptides by micro high performance liquid chromatography. The experimental parameters are: mobile phase composition, flow rate, organic modifiers, ion-pairing agents, column temperature, the effect of packing material properties: particle size, particle porosity and reversed-phase (RP) alkyl chain length, and column dimensions. When a mass spectrometer (MS) is used as the detector in micro-HPLC, certain experimental parameters such as mobile phase flow rate and buffer composition have to be adjusted in order to meet the requirements of the MS procedure employed. When electrospray ionization (ESI) is the selected MS mode of operation the mobile phase flow rate should be in nL min super(-1) and a volatile buffer should be used to achieve maximum sensitivity. Also, it was found that the elution order (selectivity) of peptides in RP-HPLC is affected by type and concentration of ion-pairing agent, organic modifier, column temperature, pH of the buffer, and the alkyl chain length of the derivatizing agent in RP. This manuscript includes work that has been done in our laboratory and is supplemented by data published by other researchers. JF - Journal of Liquid Chromatography & Related Technologies AU - Issaq, HJ AU - Fox, S D AU - Mahadevan, M AU - Conrads, T P AU - Veenstra, T D AD - Analytical Chemistry Laboratory, SAIC-Frederick, Inc., NCI-Frederick, P.O. Box B, Frederick, MD 21702-1201, USA, issaqh@ncifcrf.gov Y1 - 2003/08// PY - 2003 DA - Aug 2003 SP - 2255 EP - 2283 VL - 26 IS - 14 SN - 1082-6076, 1082-6076 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Particle size KW - Temperature effects KW - High-performance liquid chromatography KW - Liquid chromatography KW - Volatiles KW - Porosity KW - proteomics KW - pH effects KW - Ionization KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17842285?accountid=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+Liquid+Chromatography+%26+Related+Technologies&rft.atitle=Effect+of+Experimental+Parameters+on+the+HPLC+Separation+of+Peptides+and+Proteins&rft.au=Issaq%2C+HJ%3BFox%2C+S+D%3BMahadevan%2C+M%3BConrads%2C+T+P%3BVeenstra%2C+T+D&rft.aulast=Issaq&rft.aufirst=HJ&rft.date=2003-08-01&rft.volume=26&rft.issue=14&rft.spage=2255&rft.isbn=&rft.btitle=&rft.title=Journal+of+Liquid+Chromatography+%26+Related+Technologies&rft.issn=10826076&rft_id=info:doi/10.1081%2FJLC-120023246 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Proteomics. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - High-performance liquid chromatography; Temperature effects; Volatiles; Particle size; Porosity; Ionization; pH effects; proteomics; Liquid chromatography DO - http://dx.doi.org/10.1081/JLC-120023246 ER - TY - JOUR T1 - A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. AN - 73530388; 12890841 AB - Mutations in the tumor-suppressor gene VHL cause oversecretion of vascular endothelial growth factor by clear-cell renal carcinomas. We conducted a clinical trial to evaluate bevacizumab, a neutralizing antibody against vascular endothelial growth factor, in patients with metastatic renal-cell carcinoma. A randomized, double-blind, phase 2 trial was conducted comparing placebo with bevacizumab at doses of 3 and 10 mg per kilogram of body weight, given every two weeks; the time to progression of disease and the response rate were primary end points. Crossover from placebo to antibody treatment was allowed, and survival was a secondary end point. Minimal toxic effects were seen, with hypertension and asymptomatic proteinuria predominating. The trial was stopped after the interim analysis met the criteria for early stopping. With 116 patients randomly assigned to treatment groups (40 to placebo, 37 to low-dose antibody, and 39 to high-dose antibody), there was a significant prolongation of the time to progression of disease in the high-dose--antibody group as compared with the placebo group (hazard ratio, 2.55; P0.20 for all comparisons). Bevacizumab can significantly prolong the time to progression of disease in patients with metastatic renal-cell cancer. Copyright 2003 Massachusetts Medical Society JF - The New England journal of medicine AU - Yang, James C AU - Haworth, Leah AU - Sherry, Richard M AU - Hwu, Patrick AU - Schwartzentruber, Douglas J AU - Topalian, Suzanne L AU - Steinberg, Seth M AU - Chen, Helen X AU - Rosenberg, Steven A AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md 20892, USA. james_yang@nih.gov Y1 - 2003/07/31/ PY - 2003 DA - 2003 Jul 31 SP - 427 EP - 434 VL - 349 IS - 5 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Humanized KW - Endothelial Growth Factors KW - Intercellular Signaling Peptides and Proteins KW - Lymphokines KW - Tumor Suppressor Proteins KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Bevacizumab KW - 2S9ZZM9Q9V KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - Ligases KW - EC 6.- KW - VHL protein, human KW - EC 6.3.2.- KW - Abridged Index Medicus KW - Index Medicus KW - Adenocarcinoma, Clear Cell -- genetics KW - Ligases -- genetics KW - Double-Blind Method KW - Lymphatic Metastasis KW - Genes, Tumor Suppressor KW - Humans KW - Disease Progression KW - Adenocarcinoma, Clear Cell -- drug therapy KW - Intercellular Signaling Peptides and Proteins -- immunology KW - Neovascularization, Pathologic -- drug therapy KW - Adenocarcinoma, Clear Cell -- secondary KW - Middle Aged KW - Male KW - Female KW - Kidney Neoplasms -- genetics KW - Kidney Neoplasms -- drug therapy KW - Kidney Neoplasms -- pathology KW - Lymphokines -- immunology KW - Lymphokines -- antagonists & inhibitors KW - Carcinoma, Renal Cell -- drug therapy KW - Antibodies, Monoclonal -- therapeutic use KW - Endothelial Growth Factors -- immunology KW - Carcinoma, Renal Cell -- secondary KW - Antibodies, Monoclonal -- adverse effects KW - Carcinoma, Renal Cell -- genetics KW - Endothelial Growth Factors -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73530388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=A+randomized+trial+of+bevacizumab%2C+an+anti-vascular+endothelial+growth+factor+antibody%2C+for+metastatic+renal+cancer.&rft.au=Yang%2C+James+C%3BHaworth%2C+Leah%3BSherry%2C+Richard+M%3BHwu%2C+Patrick%3BSchwartzentruber%2C+Douglas+J%3BTopalian%2C+Suzanne+L%3BSteinberg%2C+Seth+M%3BChen%2C+Helen+X%3BRosenberg%2C+Steven+A&rft.aulast=Yang&rft.aufirst=James&rft.date=2003-07-31&rft.volume=349&rft.issue=5&rft.spage=427&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-04 N1 - Date created - 2003-07-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biometrics. 1979 Sep;35(3):549-56 [497341] Nature. 1999 May 20;399(6733):271-5 [10353251] Prostate. 1998 Apr 1;35(1):1-10 [9537593] J Clin Oncol. 1999 Aug;17(8):2541-5 [10561320] Development. 2000 Apr;127(7):1445-53 [10704390] J Clin Oncol. 2001 Feb 1;19(3):843-50 [11157038] Cancer Res. 2001 Jul 15;61(14):5511-6 [11454700] Clin Cancer Res. 2001 Nov;7(11):3366-74 [11705849] Cancer Res. 2002 May 15;62(10):2957-61 [12019178] Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13459-64 [12351678] J Mol Med (Berl). 1999 Jul;77(7):527-43 [10494799] Nature. 1993 Apr 29;362(6423):841-4 [7683111] Nat Genet. 1994 May;7(1):85-90 [7915601] Biochim Biophys Acta. 1996 Mar 18;1242(3):201-10 [8603073] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10589-94 [8855222] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10595-9 [8855223] Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9102-7 [9256442] Mol Cell Biol. 1997 Sep;17(9):5629-39 [9271438] Cancer Res. 1997 Oct 15;57(20):4593-9 [9377574] Comment In: Curr Oncol Rep. 2004 Mar;6(2):85-6 [14751083] N Engl J Med. 2003 Oct 23;349(17):1674 [14573745] N Engl J Med. 2003 Jul 31;349(5):419-21 [12890838] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Do bisphosphonates make children's bones better or brittle? AN - 73511488; 12890840 JF - The New England journal of medicine AU - Marini, Joan C AD - Heritable Disorders Branch, National Institute of Child Health and Human Development, Bethesda, Md, USA. Y1 - 2003/07/31/ PY - 2003 DA - 2003 Jul 31 SP - 423 EP - 426 VL - 349 IS - 5 KW - Diphosphonates KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Gaucher Disease -- drug therapy KW - Osteoporosis -- drug therapy KW - Osteogenesis Imperfecta -- drug therapy KW - Child KW - Bone Density -- drug effects KW - Diphosphonates -- therapeutic use KW - Diphosphonates -- adverse effects KW - Osteopetrosis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73511488?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Do+bisphosphonates+make+children%27s+bones+better+or+brittle%3F&rft.au=Marini%2C+Joan+C&rft.aulast=Marini&rft.aufirst=Joan&rft.date=2003-07-31&rft.volume=349&rft.issue=5&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-04 N1 - Date created - 2003-07-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 2003 Nov 20;349(21):2068-71; author reply 2068-71 [14627793] N Engl J Med. 2003 Nov 20;349(21):2068-71; author reply 2068-71 [14631922] Comment On: N Engl J Med. 2003 Jul 31;349(5):457-63 [12890844] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the DNA damage-inducible helicase DinG from Escherichia coli. AN - 73494107; 12748189 AB - The dinG promoter was first isolated in a genetic screen scoring for damage-inducible loci in Escherichia coli (Lewis, L. K., Jenkins, M. E., and Mount, D. W. (1992) J. Bacteriol. 174, 3377-3385). Sequence analysis suggests that the dinG gene encodes a putative helicase related to a group of eukaryotic helicases that includes mammalian XPD (Koonin, E. V. (1993) Nucleic Acids Res. 21, 1497), an enzyme involved in transcription-coupled nucleotide excision repair and basal transcription. We have characterized the dinG gene product from E. coli using genetic and biochemical approaches. Deletion of dinG has no severe phenotype, indicating that it is non-essential for cell viability. Both dinG deletion and over-expression of the DinG protein from a multicopy plasmid result in a slight reduction of UV resistance. DinG, purified as a fusion protein from E. coli cells, behaves as a monomer in solution, as judged from gel filtration experiments. DinG is an ATP-hydrolyzing enzyme; single-stranded (ss) DNA stimulates the ATPase activity 15-fold. Kinetic data yield a Hill coefficient of 1, consistent with one ATP-hydrolyzing site per DinG molecule. DinG possesses a DNA helicase activity; it translocates along ssDNA in a 5' --> 3' direction, as revealed in experiments with substrates containing non-natural 5'-5' and 3'-3' linkages. The ATP-dependent DNA helicase activity of DinG requires divalent cations (Mg2+, Ca2+, and Mn2+) but is not observed in the presence of Zn2+. The DinG helicase does not discriminate between ribonucleotide and deoxyribonucleotide triphosphates, and it unwinds duplex DNA with similar efficiency in the presence of ATP or dATP. We discuss the possible involvement of the DinG helicase in DNA replication and repair processes. JF - The Journal of biological chemistry AU - Voloshin, Oleg N AU - Vanevski, Filip AU - Khil, Pavel P AU - Camerini-Otero, R Daniel AD - Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/07/25/ PY - 2003 DA - 2003 Jul 25 SP - 28284 EP - 28293 VL - 278 IS - 30 SN - 0021-9258, 0021-9258 KW - Cations KW - 0 KW - Escherichia coli Proteins KW - dinG protein, E coli KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Ultraviolet Rays KW - Plasmids -- metabolism KW - DNA Repair KW - Genome, Bacterial KW - Dose-Response Relationship, Drug KW - Electrophoresis, Polyacrylamide Gel KW - Hydrogen-Ion Concentration KW - DNA -- metabolism KW - Transcription, Genetic KW - Amino Acid Sequence KW - Dose-Response Relationship, Radiation KW - Models, Biological KW - Hydrolysis KW - Gene Deletion KW - Cell Survival KW - Phenotype KW - Base Sequence KW - Amino Acid Motifs KW - Chromatography, Gel KW - Kinetics KW - Adenosine Triphosphate -- metabolism KW - Molecular Sequence Data KW - Time Factors KW - Escherichia coli Proteins -- chemistry KW - Escherichia coli Proteins -- metabolism KW - Escherichia coli -- metabolism KW - Escherichia coli -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73494107?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+the+DNA+damage-inducible+helicase+DinG+from+Escherichia+coli.&rft.au=Voloshin%2C+Oleg+N%3BVanevski%2C+Filip%3BKhil%2C+Pavel+P%3BCamerini-Otero%2C+R+Daniel&rft.aulast=Voloshin&rft.aufirst=Oleg&rft.date=2003-07-25&rft.volume=278&rft.issue=30&rft.spage=28284&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 - 2003-08-26 N1 - Date created - 2003-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast Cancer Following Radiotherapy and Chemotherapy Among Young Women With Hodgkin Disease AN - 18878297; 5737680 AB - Second cancer is the leading cause of death in long-term survivors of Hodgkin disease (HD), with exceptionally high risks of breast cancer among women treated at a young age. Quantitative associations between radiotherapy dose delivered to the breast and administered chemotherapy have not been reported to date in large series, nor has the influence of ovarian exposures on subsequent risk. To quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD. Matched case-control study of breast cancer within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger, between January 1, 1965, and December 31, 1994, and within 6 population-based cancer registries. The study was conducted March 1, 1996, through September 30, 1998. Relative risk (RR) of breast cancer associated with radiation dose delivered to site of breast cancer or to ovaries and with cumulative dose of alkylating agents. Breast cancer occurred in 105 patients with HD who were matched to 266 patients with HD but without breast cancer. A radiation dose of 4 Gy or more delivered to the breast was associated with a 3.2-fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40 Gy (P<.001 for trend). Radiation risk did not vary appreciably by age at exposure or reproductive history. Increased risks persisted for 25 or more years following radiotherapy (RR, 2.3; 95% CI, 0.5-16.5; P = .03 for trend with dose). Treatment with alkylating agents alone resulted in a reduced risk (RR, 0.6; 95% CI, 0.2-2.0) of breast cancer, and combined alkylating agents and radiotherapy in a 1.4-fold (95% CI, 0.6-3.5). increased risk. Risk of breast cancer decreased with increasing number of alkylating agent cycles (P = .003 for trend). Risk also was low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses. Hormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation. The high radiation-related risk, which did not diminish at the highest doses or the longest follow-up, however, suggests the need for lifetime surveillance and programs of patient and public awareness. JF - Journal of the American Medical Association AU - Travis, L B AU - Hill, DA AU - Dores, G M AU - Gospodarowicz, M AU - van Leeuwen, FE AU - Holowaty, E AU - Glimelius, B AU - Andersson, M AU - Wiklund, T AU - Lynch, C F AU - Veer, MBV AU - Glimelius, I AU - Storm, H AU - Pukkala, E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA Y1 - 2003/07/23/ PY - 2003 DA - 2003 Jul 23 SP - 465 EP - 475 VL - 290 IS - 4 SN - 0098-7484, 0098-7484 KW - man KW - Toxicology Abstracts KW - X 24210:Radiation & radioactive materials KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18878297?accountid=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+the+American+Medical+Association&rft.atitle=Breast+Cancer+Following+Radiotherapy+and+Chemotherapy+Among+Young+Women+With+Hodgkin+Disease&rft.au=Travis%2C+L+B%3BHill%2C+DA%3BDores%2C+G+M%3BGospodarowicz%2C+M%3Bvan+Leeuwen%2C+FE%3BHolowaty%2C+E%3BGlimelius%2C+B%3BAndersson%2C+M%3BWiklund%2C+T%3BLynch%2C+C+F%3BVeer%2C+MBV%3BGlimelius%2C+I%3BStorm%2C+H%3BPukkala%2C+E&rft.aulast=Travis&rft.aufirst=L&rft.date=2003-07-23&rft.volume=290&rft.issue=4&rft.spage=465&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Association&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The two faces of transforming growth factor beta in carcinogenesis. AN - 73561133; 12861075 JF - Proceedings of the National Academy of Sciences of the United States of America AU - Roberts, Anita B AU - Wakefield, Lalage M AD - Laboratory of Cell Regulation and Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5055, USA. robertsa@dce41.nci.nih.gov Y1 - 2003/07/22/ PY - 2003 DA - 2003 Jul 22 SP - 8621 EP - 8623 VL - 100 IS - 15 SN - 0027-8424, 0027-8424 KW - Transforming Growth Factor beta KW - 0 KW - Tumor Suppressor Proteins KW - Index Medicus KW - Animals KW - Genes, Tumor Suppressor KW - Humans KW - Mammary Neoplasms, Experimental -- physiopathology KW - Mammary Neoplasms, Experimental -- genetics KW - Mammary Neoplasms, Experimental -- etiology KW - Mice KW - Models, Biological KW - Oncogenes KW - Neoplasm Metastasis -- genetics KW - Tumor Suppressor Proteins -- physiology KW - Neoplasm Metastasis -- physiopathology KW - Neoplasm Metastasis -- therapy KW - Signal Transduction KW - Female KW - Transforming Growth Factor beta -- physiology KW - Neoplasms -- physiopathology KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73561133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+two+faces+of+transforming+growth+factor+beta+in+carcinogenesis.&rft.au=Roberts%2C+Anita+B%3BWakefield%2C+Lalage+M&rft.aulast=Roberts&rft.aufirst=Anita&rft.date=2003-07-22&rft.volume=100&rft.issue=15&rft.spage=8621&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 - 2003-09-02 N1 - Date created - 2003-07-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):992-9 [11158583] Histopathology. 2000 Feb;36(2):168-77 [10672063] Breast Cancer Res Treat. 2001 Jan;65(2):101-10 [11261825] N Engl J Med. 2001 Apr 19;344(16):1196-206 [11309634] Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4498-503 [11287649] Trends Cell Biol. 2001 Nov;11(11):S44-51 [11684442] EMBO J. 2002 Jan 15;21(1-2):145-56 [11782434] Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):159-68 [10708963] J Natl Cancer Inst. 2000 Sep 6;92(17):1388-402 [10974075] Cell. 2000 Oct 13;103(2):295-309 [11057902] Int J Cancer. 2001 Jan 1;91(1):76-82 [11149423] Immunol Ser. 1990;51:217-43 [2095919] Cell Regul. 1990 Nov;1(12):875-82 [2100192] Am J Pathol. 1993 Aug;143(2):381-9 [8393616] Cancer Res. 1996 Aug 15;56(16):3645-50 [8706000] Nat Med. 1998 Jul;4(7):802-7 [9662371] J Clin Invest. 1999 Jan;103(2):197-206 [9916131] Cancer Res. 1999 Jul 15;59(14):3379-86 [10416598] Curr Opin Genet Dev. 2002 Feb;12(1):22-9 [11790550] J Cell Biol. 2002 Jan 21;156(2):299-313 [11790801] Mol Pharmacol. 2002 Jul;62(1):65-74 [12065756] J Clin Invest. 2002 Jun;109(12):1551-9 [12070302] J Clin Invest. 2002 Jun;109(12):1607-15 [12070308] J Biol Chem. 2002 Jul 5;277(27):24571-8 [11964407] Nat Cell Biol. 2002 Jul;4(7):487-94 [12105419] Nat Rev Cancer. 2002 Aug;2(8):563-72 [12154349] Am J Pathol. 2002 Sep;161(3):749-53 [12213701] Bioessays. 2002 Oct;24(10):885-93 [12325121] Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8430-5 [12808151] Science. 1987 Jan 9;235(4785):177-82 [3798106] Cancer Surv. 1985;4(4):683-705 [2890434] Proc Natl Acad Sci U S A. 1990 Oct;87(19):7678-82 [2217201] J Natl Cancer Inst. 1999 Dec 15;91(24):2096-101 [10601380] Nat Med. 2000 Jan;6(1):100-2 [10613833] Comment On: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8430-5 [12808151] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Poly( gamma -D-glutamic acid) protein conjugates induce IgG antibodies in mice to the capsule of Bacillus anthracis: A potential addition to the anthrax vaccine AN - 18800314; 5667564 AB - Both the protective antigen (PA) and the poly( gamma -D-glutamic acid) capsule ( gamma DPGA) are essential for the virulence of Bacillus anthracis. A critical level of vaccine-induced IgG anti-PA confers immunity to anthrax, but there is no information about the protective action of IgG anti- gamma DPGA. Because the number of spores presented by bioterrorists might be greater than encountered in nature, we sought to induce capsular antibodies to expand the immunity conferred by available anthrax vaccines. The nonimmunogenic gamma DPGA or corresponding synthetic peptides were bound to BSA, recombinant B. anthracis PA (rPA), or recombinant Pseudomonas aeruginosa exotoxin A (rEPA). To identify the optimal construct, conjugates of B. anthracis gamma DPGA, Bacillus pumilus gamma DLPGA, and peptides of varying lengths (5-, 10-, or 20-mers), of the D or L configuration with active groups at the N or C termini, were bound at 5-32 mol per protein. The conjugates were characterized by physico-chemical and immunological assays, including GLC-MS and matrix-assisted laser desorption ionization time-of-flight spectrometry, and immunogenicity in 5- to 6-week-old mice. IgG anti- gamma DPGA and antiprotein were measured by ELISA. The highest levels of IgG anti- gamma DPGA were elicited by decamers of gamma DPGA at 10 -20 mol per protein bound to the N- or C-terminal end. High IgG anti- gamma DPGA levels were elicited by two injections of 2.5 mu g of gamma DPGA per mouse, whereas three injections were needed to achieve high levels of protein antibodies. rPA was the most effective carrier. Anti- gamma DPGA induced opsonophagocytic killing of B. anthracis tox-, cap+. gamma DPGA conjugates may enhance the protection conferred by PA alone. gamma DPGA-rPA conjugates induced both anti-PA and anti- gamma DPGA. JF - Proceedings of the National Academy of Sciences, USA AU - Schneerson, R AU - Kubler-Kielb, J AU - Liu, T-Y AU - Dai, Z-D AU - Leppla, SH AU - Yergey, A AU - Backlund, P AU - Shiloach, J AU - Majadly, F AU - Robbins, J B AD - National Institute of Child Health and Human Development, National Institute of Diabetes and Digestive and Kidney Diseases, and National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, schneerr@mail.nih.gov Y1 - 2003/07/22/ PY - 2003 DA - 2003 Jul 22 SP - 8945 EP - 8950 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 15 SN - 0027-8424, 0027-8424 KW - mice KW - poly- gamma -glutamic acid KW - polyglutamic acid KW - protective antigen KW - synthetic peptides KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts B: Bacteriology; Bioengineering Abstracts KW - J 02834:Vaccination and immunization KW - W4 240:Bioterrorism & Biological Warfare KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18800314?accountid=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=Poly%28+gamma+-D-glutamic+acid%29+protein+conjugates+induce+IgG+antibodies+in+mice+to+the+capsule+of+Bacillus+anthracis%3A+A+potential+addition+to+the+anthrax+vaccine&rft.au=Schneerson%2C+R%3BKubler-Kielb%2C+J%3BLiu%2C+T-Y%3BDai%2C+Z-D%3BLeppla%2C+SH%3BYergey%2C+A%3BBacklund%2C+P%3BShiloach%2C+J%3BMajadly%2C+F%3BRobbins%2C+J+B&rft.aulast=Schneerson&rft.aufirst=R&rft.date=2003-07-22&rft.volume=100&rft.issue=15&rft.spage=8945&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.1633512100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.1633512100 ER - TY - JOUR T1 - Chronic treatment with carvedilol improves ventricular function and reduces myocyte apoptosis in an animal model of heart failure. AN - 71318493; 12873352 AB - Beta blocker treatment has emerged as an effective treatment modality for heart failure. Interestingly, beta-blockers can activate both pro-apoptotic and anti-apoptotic pathways. Nevertheless, the mechanism for improved cardiac function seen with beta-blocker treatment remains largely unknown. Carvedilol is a non-selective beta-blocker with alpha-receptor blockade and antioxidant properties. We therefore studied the impact of the effects of carvedilol in an animal model of end-stage heart failure. To test whether chronic treatment with beta-blockade decreases apoptosis, we treated myopathic turkeys with two dosages of carvedilol, 1 mg/kg (DCM1) and 20 mg/kg (DCM20), for four weeks and compared them to non-treated DCM animals (DCM0) and to control turkeys (CON). Echocardiographic measurements showed that non-treated DCM animals had a significantly lower fractional shortening (FS) when compared to CON (68.73 +/- 1.37 vs. 18.76 +/- 0.59%, p < 0.001). Both doses of carvedilol significantly improved FS (33.83 +/- 10.11 and 27.73 +/- 6.18% vs. 18.76 +/- 0.59% for untreated DCM, p < 0.001). DCM left ventricles were characterized by a higher percentage of apoptotic nuclei when compared to CON (5.64 +/- 0.49 vs. 1.72 +/- 0.12%, respectively p < 0.001). Both doses of carvedilol significantly reduced the number of apoptotic nuclei (2.32 +/- 0.23% and 2.36 +/-6% 1 mg and 20 mg/kg respectively). Carvedilol improves ventricular function. Furthermore, treatment with carvedilol decreased the incidence of apoptosis in cardiac myocytes from failing hearts at both doses. These data suggest that the inhibition of apoptosis with carvedilol may lead to improvement in ventricular function and may underlie a beneficial effect of beta-blockade independent of heart rate lowering effects. JF - BMC physiology AU - Okafor, Chukwuka C AU - Perreault-Micale, Cynthia AU - Hajjar, Roger J AU - Lebeche, Djamel AU - Skiroman, Klara AU - Jabbour, George AU - Doye, Angelia A AU - Lee, Michael X AU - Laste, Nancy AU - Gwathmey, Judith K AD - Boston University Medical Center, Boston, USA. okaforc1@mail.nih.gov Y1 - 2003/07/21/ PY - 2003 DA - 2003 Jul 21 SP - 6 VL - 3 KW - Adrenergic alpha-Antagonists KW - 0 KW - Adrenergic beta-Antagonists KW - Antioxidants KW - Carbazoles KW - Propanolamines KW - carvedilol KW - 0K47UL67F2 KW - Furazolidone KW - 5J9CPU3RE0 KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Turkeys KW - Disease Models, Animal KW - Adrenergic alpha-Antagonists -- therapeutic use KW - Cardiomyopathies -- pathology KW - Cardiomyopathies -- drug therapy KW - Ventricular Dysfunction -- chemically induced KW - Antioxidants -- therapeutic use KW - Cardiomyopathies -- chemically induced KW - Ventricular Dysfunction -- pathology KW - Ventricular Dysfunction -- drug therapy KW - Furazolidone -- adverse effects KW - Adrenergic beta-Antagonists -- therapeutic use KW - Drug Evaluation, Preclinical KW - Propanolamines -- therapeutic use KW - Heart Failure -- prevention & control KW - Ventricular Function -- drug effects KW - Apoptosis -- drug effects KW - Muscle Cells -- cytology KW - Heart Failure -- chemically induced KW - Ventricular Function -- physiology KW - Carbazoles -- therapeutic use KW - Muscle Cells -- drug effects KW - Heart Failure -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71318493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+physiology&rft.atitle=Chronic+treatment+with+carvedilol+improves+ventricular+function+and+reduces+myocyte+apoptosis+in+an+animal+model+of+heart+failure.&rft.au=Okafor%2C+Chukwuka+C%3BPerreault-Micale%2C+Cynthia%3BHajjar%2C+Roger+J%3BLebeche%2C+Djamel%3BSkiroman%2C+Klara%3BJabbour%2C+George%3BDoye%2C+Angelia+A%3BLee%2C+Michael+X%3BLaste%2C+Nancy%3BGwathmey%2C+Judith+K&rft.aulast=Okafor&rft.aufirst=Chukwuka&rft.date=2003-07-21&rft.volume=3&rft.issue=&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=BMC+physiology&rft.issn=1472-6793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-12 N1 - Date created - 2003-10-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Cardiol. 1996 Oct 1;78(7):779-84 [8857482] Circulation. 1999 Jul 27;100(4):346-53 [10421593] Circulation. 1996 Dec 1;94(11):2807-16 [8941106] J Clin Invest. 1996 Dec 15;98(12):2854-65 [8981934] Circulation. 1997 Feb 18;95(4):782-6 [9054728] N Engl J Med. 1997 Apr 17;336(16):1131-41 [9099657] J Mol Cell Cardiol. 1997 Mar;29(3):859-70 [9152847] Am J Physiol. 1997 May;272(5 Pt 2):H2313-9 [9176300] Circ Res. 1997 Aug;81(2):137-44 [9242174] Curr Top Dev Biol. 1998;36:259-78 [9342533] J Clin Invest. 1998 Apr 1;101(7):1326-42 [9525975] Circ Res. 1998 Jun 15;82(11):1111-29 [9633912] Curr Opin Cardiol. 1998 Sep;13(5):317-25 [9823788] J Am Coll Cardiol. 2000 Nov 1;36(5):1698-705 [11079679] J Am Coll Cardiol. 2000 Dec;36(7):2081-9 [11127444] J Cell Physiol. 2001 Dec;189(3):257-65 [11748583] Avian Dis. 1972 Jul-Sep;16(4):958-61 [4263470] Avian Dis. 1974 Jan-Mar;18(1):125-33 [4814551] Circulation. 1991 Jun;83(6):2021-8 [1674900] Circulation. 1992 Feb;85(2):790-804 [1370925] Annu Rev Physiol. 1993;55:77-95 [8466192] Circ Res. 1993 Dec;73(6):1077-89 [8222079] Cardiovasc Res. 1993 Dec;27(12):2212-21 [8313431] J Am Coll Cardiol. 1994 Mar 1;23(3):814-21 [7906702] Immunol Today. 1994 Jan;15(1):7-10 [8136014] Circulation. 1994 Jun;89(6):2852-9 [8205701] J Am Coll Cardiol. 1995 Apr;25(5):1154-61 [7897129] J Am Coll Cardiol. 1995 May;25(6):1225-31 [7722114] Clin Cardiol. 1995 Sep;18(9 Suppl 4):IV36-44 [7489619] Lab Invest. 1995 Dec;73(6):771-87 [8558838] Am J Pathol. 1996 Jan;148(1):141-9 [8546201] N Engl J Med. 1996 May 23;334(21):1349-55 [8614419] J Clin Invest. 1996 Jun 15;97(12):2891-7 [8675703] N Engl J Med. 1996 Oct 17;335(16):1182-9 [8815940] N Engl J Med. 1998 Dec 10;339(24):1759-65 [9845712] Am J Physiol. 1999 May;276(5 Pt 2):H1678-90 [10330254] J Am Coll Cardiol. 1999 Jun;33(7):1926-34 [10362195] Circulation. 1996 Nov 1;94(9):2285-96 [8901684] N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Children's health and the environment AN - 39779963; 3772885 AU - Suk, W Y1 - 2003/07/21/ PY - 2003 DA - 2003 Jul 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39779963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Children%27s+health+and+the+environment&rft.au=Suk%2C+W&rft.aulast=Suk&rft.aufirst=W&rft.date=2003-07-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: John Wiley & Sons, Ltd., Baffins Lane, Chichester, W. Sussex PO19 1UD, UK; URL: www.wiley.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Proteomic analysis of cancers AN - 39724118; 3772904 AU - Petricoin, E F Y1 - 2003/07/21/ PY - 2003 DA - 2003 Jul 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39724118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Proteomic+analysis+of+cancers&rft.au=Petricoin%2C+E+F&rft.aulast=Petricoin&rft.aufirst=E&rft.date=2003-07-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: John Wiley & Sons, Ltd., Baffins Lane, Chichester, W. Sussex PO19 1UD, UK; URL: www.wiley.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Toxicogenomic classification of toxic effects AN - 39716084; 3772900 AU - Tennant, R Y1 - 2003/07/21/ PY - 2003 DA - 2003 Jul 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39716084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Toxicogenomic+classification+of+toxic+effects&rft.au=Tennant%2C+R&rft.aulast=Tennant&rft.aufirst=R&rft.date=2003-07-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: John Wiley & Sons, Ltd., Baffins Lane, Chichester, W. Sussex PO19 1UD, UK; URL: www.wiley.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - PhiX and other transgenic mutation systems AN - 39716022; 3772884 AU - Malling, H V Y1 - 2003/07/21/ PY - 2003 DA - 2003 Jul 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39716022?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=PhiX+and+other+transgenic+mutation+systems&rft.au=Malling%2C+H+V&rft.aulast=Malling&rft.aufirst=H&rft.date=2003-07-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: John Wiley & Sons, Ltd., Baffins Lane, Chichester, W. Sussex PO19 1UD, UK; URL: www.wiley.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Overview of base excision repair AN - 39669347; 3772917 AU - Wilson, SH Y1 - 2003/07/21/ PY - 2003 DA - 2003 Jul 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39669347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Overview+of+base+excision+repair&rft.au=Wilson%2C+SH&rft.aulast=Wilson&rft.aufirst=SH&rft.date=2003-07-21&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: John Wiley & Sons, Ltd., Baffins Lane, Chichester, W. Sussex PO19 1UD, UK; URL: www.wiley.com N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - A trade-off in replication in mosquito versus mammalian systems conferred by a point mutation in the NS4B protein of dengue virus type 4. AN - 73504148; 12890635 AB - An acceptable live-attenuated dengue virus vaccine candidate should have low potential for transmission by mosquitoes. We have identified and characterized a mutation in dengue virus type 4 (DEN4) that decreases the ability of the virus to infect mosquitoes. A panel of 1248 mutagenized virus clones generated previously by chemical mutagenesis was screened for decreased replication in mosquito C6/36 cells but efficient replication in simian Vero cells. One virus met these criteria and contained a single coding mutation: a C-to-U mutation at nucleotide 7129 resulting in a Pro-to-Leu change in amino acid 101 of the nonstructural 4B gene (NS4B P101L). This mutation results in decreased replication in C6/36 cells relative to wild-type DEN4, decreased infectivity for mosquitoes, enhanced replication in Vero and human HuH-7 cells, and enhanced replication in SCID mice implanted with HuH-7 cells (SCID-HuH-7 mice). A recombinant DEN4 virus (rDEN4) bearing this mutation exhibited the same set of phenotypes. Addition of the NS4B P101L mutation to rDEN4 bearing a 30 nucleotide deletion (Delta30) decreased the ability of the double-mutant virus to infect mosquitoes but increased its ability to replicate in SCID-HuH-7 mice. Although the NS4B P101L mutation decreases infectivity of DEN4 for mosquitoes, its ability to enhance replication in SCID-HuH-7 mice suggests that it might not be advantageous to include this specific mutation in an rDEN4 vaccine. The opposing effects of the NS4B P101L mutation in mosquito and vertebrate systems suggest that the NS4B protein is involved in maintaining the balance between efficient replication in the mosquito vector and the human host. JF - Virology AU - Hanley, Kathryn A AU - Manlucu, Luella R AU - Gilmore, Lara E AU - Blaney, Joseph E AU - Hanson, Christopher T AU - Murphy, Brian R AU - Whitehead, Stephen S AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. khanley@niaid.nih.gov Y1 - 2003/07/20/ PY - 2003 DA - 2003 Jul 20 SP - 222 EP - 232 VL - 312 IS - 1 SN - 0042-6822, 0042-6822 KW - NS4B protein, flavivirus KW - 0 KW - Viral Nonstructural Proteins KW - Viral Vaccines KW - Index Medicus KW - Dengue -- virology KW - Animals KW - Humans KW - Viral Vaccines -- genetics KW - Insect Vectors KW - Mice KW - Mice, SCID KW - Cell Line KW - Dengue -- transmission KW - Virus Replication KW - Point Mutation -- genetics KW - Viral Nonstructural Proteins -- genetics KW - Culicidae -- virology KW - Dengue Virus -- genetics KW - Viral Nonstructural Proteins -- metabolism KW - Dengue Virus -- physiology KW - Dengue Virus -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73504148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+trade-off+in+replication+in+mosquito+versus+mammalian+systems+conferred+by+a+point+mutation+in+the+NS4B+protein+of+dengue+virus+type+4.&rft.au=Hanley%2C+Kathryn+A%3BManlucu%2C+Luella+R%3BGilmore%2C+Lara+E%3BBlaney%2C+Joseph+E%3BHanson%2C+Christopher+T%3BMurphy%2C+Brian+R%3BWhitehead%2C+Stephen+S&rft.aulast=Hanley&rft.aufirst=Kathryn&rft.date=2003-07-20&rft.volume=312&rft.issue=1&rft.spage=222&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-03 N1 - Date created - 2003-07-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Personality, substance of choice, and polysubstance involvement among substance dependent patients. AN - 73427517; 12821207 AB - The authors compared the association of several personality traits, drug of choice, and polysubstance involvement in 325 individuals (44% male) receiving treatment for substance dependence on heroin, cocaine, and/or alcohol. Measures included the Structured Clinical Interview for DSM-III-R, the MacAndrew Alcoholism Scale (MAC), the socialization scale of the California Psychological Inventory (CPI-Soc), the novelty seeking dimension of the Temperament and Character Inventory (TCI-NS), and the conscientiousness domain of the NEO Five-Factor Inventory (NEO-C). Analyses adjusted for demographic covariates, affective and antisocial personality disorder, and substance dependence severity. Although scant evidence supported the hypothesis that these personality traits were associated with substance choice, CPI-Soc and MAC were associated linearly with the extent of polysubstance involvement. Also, patients who were dependent on two or more substances displayed higher levels of TCI-NS, CPI-Soc, and MAC. Findings implicate an association between behavioral disinhibition and a continuum of addiction defined primarily in terms of polysubstance involvement. JF - Drug and alcohol dependence AU - Conway, Kevin P AU - Kane, Robert J AU - Ball, Samuel A AU - Poling, James C AU - Rounsaville, Bruce J AD - Division of Epidemiology, Services, and Prevention Research, National Institute on Drug Abuse, 6001 Executive Boulevard Suite 5153 MSC 9589, Bethesda, MD 20892-9589, USA. kconway@nida.nih.gov Y1 - 2003/07/20/ PY - 2003 DA - 2003 Jul 20 SP - 65 EP - 75 VL - 71 IS - 1 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Socioeconomic Factors KW - Diagnosis, Dual (Psychiatry) -- methods KW - Mental Disorders -- epidemiology KW - Humans KW - Chi-Square Distribution KW - Adult KW - Middle Aged KW - Mental Disorders -- psychology KW - Male KW - Female KW - Neuropsychological Tests -- statistics & numerical data KW - Choice Behavior KW - Personality KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73427517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Personality%2C+substance+of+choice%2C+and+polysubstance+involvement+among+substance+dependent+patients.&rft.au=Conway%2C+Kevin+P%3BKane%2C+Robert+J%3BBall%2C+Samuel+A%3BPoling%2C+James+C%3BRounsaville%2C+Bruce+J&rft.aulast=Conway&rft.aufirst=Kevin&rft.date=2003-07-20&rft.volume=71&rft.issue=1&rft.spage=65&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-18 N1 - Date created - 2003-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV (AUDADIS-IV): reliability of alcohol consumption, tobacco use, family history of depression and psychiatric diagnostic modules in a general population sample. AN - 73411627; 12821201 AB - the purpose of this study was to assess the test-retest reliability of newly introduced or revised modules of the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV (AUDADIS-IV), including alcohol consumption, tobacco use, family history of depression, and selected DSM-IV axis I and II psychiatric disorders. kappa and intraclass correlation coefficients were calculated for the AUDADIS-IV modules using a test-retest design among a total of 2657 respondents, in subsets of approximately 400, randomly drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). reliabilities for alcohol consumption, tobacco use and family history of major depression measures were good to excellent, while reliabilities for selected DSM-IV axis I and II disorders were fair to good. The reliabilities of dimensional symptom scales of DSM-IV axis I and axis II disorders exceeded those of their dichotomous diagnostic counterparts and were generally in the good to excellent range. the high reliability of alcohol consumption, tobacco use, family history of depression and psychiatric disorder modules found in this study suggests that the AUDADIS-IV can be a useful tool in various research settings, particularly in studies of the general population, the target population for which it was designed. JF - Drug and alcohol dependence AU - Grant, Bridget F AU - Dawson, Deborah A AU - Stinson, Frederick S AU - Chou, Patricia S AU - Kay, Ward AU - Pickering, Roger AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Suite 514, 6000 Executive Boulevard, MSC 7003, Bethesda, MD 20892-7003, USA. bgrant@willco.niaaa.nih.gov Y1 - 2003/07/20/ PY - 2003 DA - 2003 Jul 20 SP - 7 EP - 16 VL - 71 IS - 1 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Analysis of Variance KW - Reproducibility of Results KW - Alcoholism -- diagnosis KW - Humans KW - Aged KW - Alcoholism -- psychology KW - Alcoholism -- epidemiology KW - Adult KW - Middle Aged KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Adolescent KW - Diagnostic and Statistical Manual of Mental Disorders KW - Female KW - Male KW - Depressive Disorder -- epidemiology KW - Alcohol-Related Disorders -- diagnosis KW - Interview, Psychological -- methods KW - Depressive Disorder -- psychology KW - Depressive Disorder -- diagnosis KW - Alcohol Drinking -- psychology KW - Smoking -- psychology KW - Alcohol Drinking -- epidemiology KW - Smoking -- epidemiology KW - Alcohol-Related Disorders -- psychology KW - Alcohol-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73411627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=The+Alcohol+Use+Disorder+and+Associated+Disabilities+Interview+Schedule-IV+%28AUDADIS-IV%29%3A+reliability+of+alcohol+consumption%2C+tobacco+use%2C+family+history+of+depression+and+psychiatric+diagnostic+modules+in+a+general+population+sample.&rft.au=Grant%2C+Bridget+F%3BDawson%2C+Deborah+A%3BStinson%2C+Frederick+S%3BChou%2C+Patricia+S%3BKay%2C+Ward%3BPickering%2C+Roger&rft.aulast=Grant&rft.aufirst=Bridget&rft.date=2003-07-20&rft.volume=71&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-18 N1 - Date created - 2003-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) is induced by genistein through the expression of p53 in colorectal cancer cells. AN - 73317229; 12767058 AB - Genistein is an isoflavenoid found in soy that has anti-tumorigenic activities. Treatment of colorectal carcinoma HCT-116 cells with 50 microM genistein results in a 50% reduction in cell proliferation and a 6-fold increase in apoptosis. Genistein induces nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1), a protein with antitumorigenic activities, in a time- and concentration-dependent manner in HCT-116 cells. In addition, p53 and p21 are induced in HCT-116 cells. The induction of p53 (3 hr) precedes the induction of NAG-1 (12 hr), suggesting that genistein-induced NAG-1 expression is mediated by p53. In contrast, NAG-1 is not induced by genistein in the p53-negative colorectal carcinoma cell line HCT-15. Luciferase reporter constructs of the NAG-1 promoter containing 2 p53 sites showed that the p53 sites within the NAG-1 promoter are critical to genistein-induced NAG-1 expression in p53-positive U2OS cells. The expression of p53 was critical for NAG-1 promoter activity since no promoter activity was observed with genistein treatment in HCT-15 cells. However, genistein-induced promoter activity was restored in HCT-15 cells by transfection with wild-type p53. Together our data suggest a relationship between genistein, p53 and NAG-1 forming a novel pathway responsible for the antitumorigenic activity of genistein. Copyright 2003 Wiley-Liss, Inc. JF - International journal of cancer AU - Wilson, Leigh C AU - Baek, Seung Joon AU - Call, Allison AU - Eling, Thomas E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2003/07/20/ PY - 2003 DA - 2003 Jul 20 SP - 747 EP - 753 VL - 105 IS - 6 SN - 0020-7136, 0020-7136 KW - Antineoplastic Agents KW - 0 KW - Cytokines KW - GDF15 protein, human KW - Growth Differentiation Factor 15 KW - Tumor Suppressor Protein p53 KW - Genistein KW - DH2M523P0H KW - Index Medicus KW - Promoter Regions, Genetic KW - Apoptosis KW - Tumor Cells, Cultured KW - Dose-Response Relationship, Drug KW - Kinetics KW - Humans KW - Cell Division -- drug effects KW - Up-Regulation KW - Mutation KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Transcriptional Activation KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Cytokines -- genetics KW - Carcinoma -- pathology KW - Genistein -- pharmacology KW - Colorectal Neoplasms -- pathology KW - Colorectal Neoplasms -- metabolism KW - Cytokines -- biosynthesis KW - Colorectal Neoplasms -- genetics KW - Tumor Suppressor Protein p53 -- genetics KW - Carcinoma -- metabolism KW - Antineoplastic Agents -- pharmacology KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73317229?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nonsteroidal+anti-inflammatory+drug-activated+gene+%28NAG-1%29+is+induced+by+genistein+through+the+expression+of+p53+in+colorectal+cancer+cells.&rft.au=Wilson%2C+Leigh+C%3BBaek%2C+Seung+Joon%3BCall%2C+Allison%3BEling%2C+Thomas+E&rft.aulast=Wilson&rft.aufirst=Leigh&rft.date=2003-07-20&rft.volume=105&rft.issue=6&rft.spage=747&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 - 2003-07-02 N1 - Date created - 2003-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonpolar thymine isosteres in the Ty3 polypurine tract DNA template modulate processing and provide a model for its recognition by Ty3 reverse transcriptase. AN - 73528176; 12730227 AB - Despite diverging in sequence and size, the polypurine tract (PPT) primers of retroviruses and long terminal repeat-containing retrotransposons are accurately processed from (+) U3 RNA and DNA by their cognate reverse transcriptases (RTs). In this paper, we demonstrate that misalignment of the Ty3 retrotransposon RT on the human immunodeficiency virus-1 PPT induces imprecise removal of adjacent (+)-RNA and failure to release (+)-DNA from the primer. Based on these observations, we explored the structural basis of Ty3 PPT recognition by chemically synthesizing RNA/DNA hybrids whose (-)-DNA template was substituted with the non-hydrogen-bonding thymine isostere 2,4-difluoro-5-methylbenzene (F). We observed a consistent spatial correlation between the site of T --> F substitution and enhanced ribonuclease H (RNase H) activity approximately 12-13 bp downstream. In the most pronounced case, dual T --> F substitution at PPT positions -1/-2 redirects RNase H cleavage almost exclusively to the novel site. The structural features of this unusual base suggest that its insertion into the Ty3 PPT (-)-DNA template weakens the duplex, inducing a destabilization that is recognized by a structural element of Ty3 RT approximately 12-13 bp from its RNase H catalytic center. A likely candidate for this interaction is the thumb subdomain, whose minor groove binding tract most likely contacts the duplex. The spatial relationship derived from T --> F substitution also infers that Ty3 PPT processing requires recognition of sequences in its immediate 5' vicinity, thereby locating the RNase H catalytic center over the PPT-U3 junction, a notion strengthened by additional mutagenesis studies of this paper. JF - The Journal of biological chemistry AU - Lener, Daniela AU - Kvaratskhelia, Mamuka AU - Le Grice, Stuart F J AD - Resistance Mechanisms Laboratory, HIV Drug Resistance Program, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702-1201, USA. Y1 - 2003/07/18/ PY - 2003 DA - 2003 Jul 18 SP - 26526 EP - 26532 VL - 278 IS - 29 SN - 0021-9258, 0021-9258 KW - DNA, Fungal KW - 0 KW - DNA, Viral KW - RNA, Fungal KW - RNA, Viral KW - Retroelements KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - RNA-Directed DNA Polymerase KW - Ribonuclease H KW - EC 3.1.26.4 KW - Thymine KW - QR26YLT7LT KW - Index Medicus KW - Ribonuclease H -- chemistry KW - HIV-1 -- genetics KW - RNA, Fungal -- genetics KW - RNA, Fungal -- metabolism KW - Catalytic Domain KW - Ribonuclease H -- metabolism KW - Models, Biological KW - RNA Processing, Post-Transcriptional KW - Saccharomyces cerevisiae -- genetics KW - Mutagenesis, Site-Directed KW - HIV-1 -- metabolism KW - Saccharomyces cerevisiae -- metabolism KW - DNA, Viral -- chemistry KW - RNA, Viral -- chemistry KW - HIV Reverse Transcriptase -- metabolism KW - RNA, Viral -- genetics KW - RNA, Viral -- metabolism KW - DNA, Viral -- genetics KW - DNA, Viral -- metabolism KW - RNA, Fungal -- chemistry KW - Retroelements -- genetics KW - Thymine -- chemistry KW - RNA-Directed DNA Polymerase -- chemistry KW - DNA, Fungal -- genetics KW - RNA-Directed DNA Polymerase -- metabolism KW - DNA, Fungal -- metabolism KW - DNA, Fungal -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73528176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nonpolar+thymine+isosteres+in+the+Ty3+polypurine+tract+DNA+template+modulate+processing+and+provide+a+model+for+its+recognition+by+Ty3+reverse+transcriptase.&rft.au=Lener%2C+Daniela%3BKvaratskhelia%2C+Mamuka%3BLe+Grice%2C+Stuart+F+J&rft.aulast=Lener&rft.aufirst=Daniela&rft.date=2003-07-18&rft.volume=278&rft.issue=29&rft.spage=26526&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 - 2003-08-27 N1 - Date created - 2003-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased AMP:ATP ratio and AMP-activated protein kinase activity during cellular senescence linked to reduced HuR function. AN - 73457338; 12730239 AB - Cytoplasmic export of the RNA-binding protein HuR, a process that critically regulates its function, was recently shown to be inhibited by the AMP-activated protein kinase (AMPK). In the present investigation, treatment of human fibroblasts with AMPK activators such as 5-amino-imidazole-4-carboxamide riboside, antimycin A, and sodium azide inhibited cell growth and lowered the expression of proliferative genes. As anticipated, AMPK activation also decreased both the cytoplasmic HuR levels and the association of HuR with target radiolabeled transcripts encoding such proliferative genes. HuR function was previously shown to be implicated in the maintenance of a "young cell" phenotype in models of replicative cellular senescence. We therefore postulated that AMPK activation in human fibroblasts might contribute to the implementation of the senescence phenotype through mechanisms that included a reduction in HuR cytoplasmic presence. Indeed, AMP:ATP ratios were 2-3-fold higher in senescent fibroblasts compared with young fibroblasts. Accordingly, in vitro senescence was accompanied by a marked elevation in AMPK activity. Evidence that increased AMPK activity directly contributed to the implementation of the senescent phenotype was obtained through two experimental approaches. First, use of AMPK activators triggered senescence characteristics in fibroblasts, such as the acquisition of senescence-associated beta-galactosidase (beta-gal) activity and increased p16INK4a expression. Second, infection of cells with an adenoviral vector that expresses active AMPK increased senescence-associated beta-gal activity, whereas infection with an adenovirus that expresses dominant-negative AMPK decreased senescence-associated beta-gal activity. Together, our results indicate that AMPK activation can cause premature fibroblast senescence through mechanisms that likely involve reduced HuR function. JF - The Journal of biological chemistry AU - Wang, Wengong AU - Yang, Xiaoling AU - López de Silanes, Isabel AU - Carling, David AU - Gorospe, Myriam AD - Laboratory of Cellular and Molecular Biology, NIA Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2003/07/18/ PY - 2003 DA - 2003 Jul 18 SP - 27016 EP - 27023 VL - 278 IS - 29 SN - 0021-9258, 0021-9258 KW - Antigens, Surface KW - 0 KW - CCNB1 protein, human KW - Cyclin A KW - Cyclin B KW - Cyclin B1 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - ELAV Proteins KW - ELAV-Like Protein 1 KW - ELAVL1 protein, human KW - Multienzyme Complexes KW - RNA, Messenger KW - RNA-Binding Proteins KW - Recombinant Proteins KW - Ribonucleotides KW - Aminoimidazole Carboxamide KW - 360-97-4 KW - Adenosine Monophosphate KW - 415SHH325A KW - Antimycin A KW - 642-15-9 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Sodium Azide KW - 968JJ8C9DV KW - AMP-Activated Protein Kinases KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - beta-Galactosidase KW - EC 3.2.1.23 KW - AICA ribonucleotide KW - F0X88YW0YK KW - Index Medicus KW - Cyclin A -- genetics KW - Humans KW - Fibroblasts -- cytology KW - RNA, Messenger -- genetics KW - Sodium Azide -- pharmacology KW - Antimycin A -- pharmacology KW - Recombinant Proteins -- metabolism KW - Genetic Vectors KW - Enzyme Activation -- drug effects KW - Ribonucleotides -- pharmacology KW - Fibroblasts -- drug effects KW - Cyclin-Dependent Kinase Inhibitor p16 -- metabolism KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Fibroblasts -- metabolism KW - Adenoviridae -- genetics KW - Base Sequence KW - beta-Galactosidase -- metabolism KW - RNA, Messenger -- metabolism KW - Transfection KW - Cyclin B -- genetics KW - Protein Binding -- drug effects KW - Genes, fos KW - Cell Line KW - Multienzyme Complexes -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - RNA-Binding Proteins -- metabolism KW - Adenosine Monophosphate -- metabolism KW - Aminoimidazole Carboxamide -- pharmacology KW - Cell Aging -- physiology KW - Aminoimidazole Carboxamide -- analogs & derivatives KW - Adenosine Triphosphate -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Multienzyme Complexes -- genetics KW - Cell Aging -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73457338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+AMP%3AATP+ratio+and+AMP-activated+protein+kinase+activity+during+cellular+senescence+linked+to+reduced+HuR+function.&rft.au=Wang%2C+Wengong%3BYang%2C+Xiaoling%3BL%C3%B3pez+de+Silanes%2C+Isabel%3BCarling%2C+David%3BGorospe%2C+Myriam&rft.aulast=Wang&rft.aufirst=Wengong&rft.date=2003-07-18&rft.volume=278&rft.issue=29&rft.spage=27016&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 - 2003-08-27 N1 - Date created - 2003-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A conformationally locked analogue of the anti-HIV agent stavudine. An important correlation between pseudorotation and maximum amplitude. AN - 73462375; 12852759 AB - The synthesis and biological evaluation of a bicyclo[3.1.0]hexene nucleoside designed as a conformational mimic of the anti-HIV agent stavudine (1, D4T) is described. The unsaturated methanocarbocyclic pseudosugar of N-MCD4T (2) was constructed from an iodo-substituted precursor by a DBU-catalyzed olefination reaction. Mitsunobu coupling with N(3)-benzoylthymine afforded the desired target after deprotection. Both D4T and N-MCD4T are in the North (N) hemisphere of the pseudorotational cycle but 70 degrees away from a perfect N (P = 0 degrees ) conformation toward the East and West hemispheres, respectively. Despite this large difference, the double bond reduces the puckering amplitude (nu(max)) of N-MCD4T to 6.81 degrees, and the superposition of both structures showed a RMS deviation of only 0.039 A. The combined structural analysis of P and nu(max) shows that while the value of P may differ substantially, the low nu(max) resolves the differences and becomes the dominant pseudorotational parameter. N-MCD4T is active against HIV-1 and HIV-2 in CEM, MT-2, and MT-4 cells, and while it is somewhat less potent than D4T, it also appears to be less toxic. The triphosphate (N-MCD4TTP) inhibits HIV reverse transcriptase with a 10-fold higher IC(50) than D4TTP. By virtue of its carbocyclic nature, N-MCD4T (2) is a more robust molecule stable to conditions that would cleave D4T. JF - Journal of medicinal chemistry AU - Choi, Yongseok AU - George, Clifford AU - Comin, Maria J AU - Barchi, Joseph J AU - Kim, Hak Sung AU - Jacobson, Kenneth A AU - Balzarini, Jan AU - Mitsuya, Hiroaki AU - Boyer, Paul L AU - Hughes, Stephen H AU - Marquez, Victor E AD - Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA. Y1 - 2003/07/17/ PY - 2003 DA - 2003 Jul 17 SP - 3292 EP - 3299 VL - 46 IS - 15 SN - 0022-2623, 0022-2623 KW - 1-(5-(hydroxymethyl)bicyclo(3.1.0)hex-3-en-2-yl)-5-methyl-1,3-dihydropyrimidine-2,4-dione KW - 0 KW - Anti-HIV Agents KW - Bridged Bicyclo Compounds KW - Reverse Transcriptase Inhibitors KW - Stavudine KW - BO9LE4QFZF KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Thymidine KW - VC2W18DGKR KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Humans KW - HIV Reverse Transcriptase -- antagonists & inhibitors KW - HIV-2 -- drug effects KW - HIV Reverse Transcriptase -- chemistry KW - Structure-Activity Relationship KW - Molecular Mimicry KW - Crystallography, X-Ray KW - Molecular Conformation KW - HIV-1 -- drug effects KW - Lymphocytes -- drug effects KW - Cell Line KW - Lymphocytes -- virology KW - Anti-HIV Agents -- chemistry KW - Reverse Transcriptase Inhibitors -- chemistry KW - Stavudine -- chemistry KW - Bridged Bicyclo Compounds -- chemical synthesis KW - Bridged Bicyclo Compounds -- chemistry KW - Thymidine -- chemistry KW - Reverse Transcriptase Inhibitors -- pharmacology KW - Stavudine -- pharmacology KW - Thymidine -- pharmacology KW - Thymidine -- chemical synthesis KW - Anti-HIV Agents -- chemical synthesis KW - Bridged Bicyclo Compounds -- pharmacology KW - Stavudine -- chemical synthesis KW - Anti-HIV Agents -- pharmacology KW - Stavudine -- analogs & derivatives KW - Reverse Transcriptase Inhibitors -- chemical synthesis KW - Thymidine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73462375?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+conformationally+locked+analogue+of+the+anti-HIV+agent+stavudine.+An+important+correlation+between+pseudorotation+and+maximum+amplitude.&rft.au=Choi%2C+Yongseok%3BGeorge%2C+Clifford%3BComin%2C+Maria+J%3BBarchi%2C+Joseph+J%3BKim%2C+Hak+Sung%3BJacobson%2C+Kenneth+A%3BBalzarini%2C+Jan%3BMitsuya%2C+Hiroaki%3BBoyer%2C+Paul+L%3BHughes%2C+Stephen+H%3BMarquez%2C+Victor+E&rft.aulast=Choi&rft.aufirst=Yongseok&rft.date=2003-07-17&rft.volume=46&rft.issue=15&rft.spage=3292&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 - 2003-08-18 N1 - Date created - 2003-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. AN - 73488122; 12867501 AB - Increasing evidence has suggested an important role for environmental toxins such as pesticides in the pathogenesis of Parkinson's disease (PD). Chronic exposure to rotenone, a common herbicide, reproduces features of Parkinsonism in rats. Mechanistically, rotenone-induced dopaminergic neurodegeneration has been associated with both its inhibition of neuronal mitochondrial complex I and the enhancement of activated microglia. Our previous studies with NADPH oxidase inhibitors, diphenylene iodonium and apocynin, suggested that NADPH oxidase-derived superoxide might be a major factor in mediating the microglia-enhanced rotenone neurotoxicity. However, because of the relatively low specificity of these inhibitors, the exact source of superoxide induced by rotenone remains to be further determined. In this study, using primary mesencephalic cultures from NADPH oxidase--null (gp91phox-/-) or wild-type (gp91phox+/+) mice, we demonstrated a critical role for microglial NADPH oxidase in mediating microglia-enhanced rotenone neurotoxicity. In neuron--glia cultures, dopaminergic neurons from gp91phox-/- mice were more resistant to rotenone neurotoxicity than those from gp91phox+/+ mice. However, in neuron-enriched cultures, the neurotoxicity of rotenone was not different between the two types of mice. More importantly, the addition of microglia prepared from gp91phox+/+ mice but not from gp91phox-/- mice to neuron-enriched cultures markedly increased rotenone-induced degeneration of dopaminergic neurons. Furthermore, apocynin attenuated rotenone neurotoxicity only in the presence of microglia from gp91phox+/+ mice. These results indicated that the greatly enhanced neurotoxicity of rotenone was attributed to the release of NADPH oxidase-derived superoxide from activated microglia. This study also suggested that microglial NADPH oxidase may be a promising target for PD treatment. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Gao, Hui-Ming AU - Liu, Bin AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences-National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. gao@niehs.nih.gov Y1 - 2003/07/16/ PY - 2003 DA - 2003 Jul 16 SP - 6181 EP - 6187 VL - 23 IS - 15 KW - Acetophenones KW - 0 KW - CYBB protein, human KW - Enzyme Inhibitors KW - Insecticides KW - Membrane Glycoproteins KW - Neuroprotective Agents KW - Rotenone KW - 03L9OT429T KW - Superoxides KW - 11062-77-4 KW - acetovanillone KW - B6J7B9UDTR KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Coculture Techniques KW - Drug Resistance -- genetics KW - Acetophenones -- pharmacology KW - Mice KW - Mesencephalon -- cytology KW - Membrane Glycoproteins -- deficiency KW - Neuroprotective Agents -- pharmacology KW - Mice, Knockout KW - Parkinson Disease -- etiology KW - Superoxides -- metabolism KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Enzyme Inhibitors -- pharmacology KW - Mesencephalon -- embryology KW - Membrane Glycoproteins -- genetics KW - NADPH Oxidase -- metabolism KW - Insecticides -- toxicity KW - Rotenone -- toxicity KW - Microglia -- enzymology KW - Neurons -- metabolism KW - Neurons -- drug effects KW - NADPH Oxidase -- antagonists & inhibitors KW - Neurons -- cytology KW - Microglia -- cytology KW - Dopamine -- pharmacokinetics KW - Dopamine -- metabolism KW - NADPH Oxidase -- genetics KW - Microglia -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73488122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Critical+role+for+microglial+NADPH+oxidase+in+rotenone-induced+degeneration+of+dopaminergic+neurons.&rft.au=Gao%2C+Hui-Ming%3BLiu%2C+Bin%3BHong%2C+Jau-Shyong&rft.aulast=Gao&rft.aufirst=Hui-Ming&rft.date=2003-07-16&rft.volume=23&rft.issue=15&rft.spage=6181&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-13 N1 - Date created - 2003-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of apoptosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin following endotoxin exposure. AN - 73510163; 12878042 AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent and persistent environmental toxin that induces hepatotoxicity and increases endotoxin-induced liver injury. The objective of this study was to evaluate whether TCDD could modulate apoptosis and cytokine-controlled apoptotic signaling pathways following lipopolysaccharide (LPS) exposure in female B6C3F1 mice. The effects of TCDD treatment were most dramatic late in the time course (10-14 days posttreatment). Serum enzyme activities were elevated at day 10 (100 microg TCDD/40 microg LPS treatment) and day 14 (100 microg TCDD/saline treatment), indicating peak liver damage occurred at those times. Histological examination of perfused livers showed an increase in apoptotic cells at day 14 in animals treated with 10 microg TCDD. Caspase-1 activity was suppressed at 14 days in mice treated with 100 microg TCDD/40 microg LPS and 100 microg TCDD/4 microg LPS compared to the respective corn oil (CO)/LPS-treated controls. Caspase-3 activity was suppressed at 14 days in 100 microg TCDD/saline-100 microg TCDD/40 microg LPS- and 100 microg TCDD/4 microg LPS-treated mice compared to respective CO/saline- or CO/LPS-treated control mice. At 40 microg LPS, caspase activity was stimulated in TCDD (100 microg)-exposed mice at 3 and 7 days and then suppressed at 10 and 14 days. Western blot analysis, electrophoretic mobility shift assay, and ELISA did not show any effect by TCDD (100 microg) on IkappaB-beta and IkappaB-alpha protein expression or on DNA binding activity of the nuclear NFkappaB protein. These data indicate that TCDD induces apoptosis 14 days posttreatment; however, we found no evidence of suppression of the antiapoptotic transcription factor NFkappaB. JF - Toxicology and applied pharmacology AU - Patterson, Rachel M AU - Stachlewitz, Robert AU - Germolec, Dori AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 2003/07/15/ PY - 2003 DA - 2003 Jul 15 SP - 120 EP - 134 VL - 190 IS - 2 SN - 0041-008X, 0041-008X KW - Environmental Pollutants KW - 0 KW - I kappa B beta protein KW - I-kappa B Proteins KW - Lipopolysaccharides KW - NF-kappa B KW - Nfkbia protein, mouse KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - Casp3 protein, mouse KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Administration, Oral KW - Animals KW - Cell Count KW - Dose-Response Relationship, Drug KW - I-kappa B Proteins -- metabolism KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Tumor Necrosis Factor-alpha -- genetics KW - Caspases -- metabolism KW - Drug Therapy, Combination KW - Mice, Inbred Strains KW - RNA, Messenger -- metabolism KW - Tumor Necrosis Factor-alpha -- metabolism KW - Time Factors KW - Female KW - NF-kappa B -- metabolism KW - Liver -- pathology KW - Liver -- enzymology KW - Environmental Pollutants -- toxicity KW - Liver -- drug effects KW - Lipopolysaccharides -- pharmacology KW - Polychlorinated Dibenzodioxins -- administration & dosage KW - Apoptosis -- drug effects KW - Polychlorinated Dibenzodioxins -- toxicity KW - Environmental Pollutants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73510163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Induction+of+apoptosis+by+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin+following+endotoxin+exposure.&rft.au=Patterson%2C+Rachel+M%3BStachlewitz%2C+Robert%3BGermolec%2C+Dori&rft.aulast=Patterson&rft.aufirst=Rachel&rft.date=2003-07-15&rft.volume=190&rft.issue=2&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-26 N1 - Date created - 2003-07-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-escalating and pharmacological study of oxaliplatin in adult cancer patients with impaired renal function: a National Cancer Institute Organ Dysfunction Working Group Study. AN - 73474314; 12860942 AB - This study was undertaken to determine the toxicities, pharmacokinetics, and maximum tolerated doses of oxaliplatin in patients with renal impairment and to develop formal guidelines for oxaliplatin dosing in this patient population. Thirty-seven adult cancer patients with variable renal function received intravenous oxaliplatin at 60 to 130 mg/m2 every 3 weeks. Patients were stratified by 24-hour creatinine clearance (CrCL) into four cohorts: group A (controls, CrCL > or =60 mL/min), group B (mild dysfunction, CrCL 40 to 59 mL/min), group C (moderate dysfunction, CrCL 20 to 39 mL/min), and group D (severe dysfunction, CrCL <20 mL/min). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. No dose-limiting toxicities were observed in any patient group during the first cycle of therapy. Escalation of oxaliplatin to the maximum dose of 130 mg/m2 was well tolerated in all patient groups with a CrCL > or =20 mL/min (groups A, B, and C). Pharmacokinetic analysis showed that patients with decreased CrCL had a corresponding decrease in the clearance of plasma ultrafiltrable platinum (r2 = 0.765). However, oxaliplatin-induced side effects were not more common or severe in patients with mild to moderate renal dysfunction, despite the decrease in ultrafiltrable platinum clearance. Oxaliplatin at 130 mg/m2 every 3 weeks is well tolerated by patients with mild to moderate degrees of renal dysfunction. These data strongly support the recommendation that dose reductions of single-agent oxaliplatin are not necessary in patients with a CrCL greater than 20 mL/min. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Takimoto, Chris H AU - Remick, Scot C AU - Sharma, Sunil AU - Mani, Sridhar AU - Ramanathan, Ramesh K AU - Doroshow, James AU - Hamilton, Anne AU - Mulkerin, Daniel AU - Graham, Martin AU - Lockwood, Graham F AU - Ivy, Percy AU - Egorin, Merrill AU - Schuler, Barbara AU - Greenslade, Denis AU - Goetz, Andrew AU - Knight, Ronald AU - Thomas, Rebecca AU - Monahan, Brian P AU - Dahut, William AU - Grem, Jean L AU - National Cancer Institute Organ Dysfunction Working Group Study AD - University of Texas Health Science Center at San Antonio, Cancer Therapy and Research Center, 7979 Wurzbach Rd, Room Z415, San Antonio, TX 78229, USA. ctakimot@idd.org. ; National Cancer Institute Organ Dysfunction Working Group Study Y1 - 2003/07/15/ PY - 2003 DA - 2003 Jul 15 SP - 2664 EP - 2672 VL - 21 IS - 14 SN - 0732-183X, 0732-183X KW - Organoplatinum Compounds KW - 0 KW - oxaliplatin KW - 04ZR38536J KW - Index Medicus KW - United States KW - Severity of Illness Index KW - Probability KW - Kidney Function Tests KW - Reference Values KW - Drug Administration Schedule KW - Neoplasm Staging KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Aged KW - Risk Assessment KW - Aged, 80 and over KW - National Institutes of Health (U.S.) KW - Adult KW - Treatment Outcome KW - Follow-Up Studies KW - Middle Aged KW - Female KW - Male KW - Survival Analysis KW - Organoplatinum Compounds -- pharmacokinetics KW - Neoplasms -- drug therapy KW - Kidney Diseases -- physiopathology KW - Organoplatinum Compounds -- administration & dosage KW - Neoplasms -- pathology KW - Neoplasms -- mortality KW - Glomerular Filtration Rate -- drug effects KW - Maximum Tolerated Dose UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73474314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dose-escalating+and+pharmacological+study+of+oxaliplatin+in+adult+cancer+patients+with+impaired+renal+function%3A+a+National+Cancer+Institute+Organ+Dysfunction+Working+Group+Study.&rft.au=Takimoto%2C+Chris+H%3BRemick%2C+Scot+C%3BSharma%2C+Sunil%3BMani%2C+Sridhar%3BRamanathan%2C+Ramesh+K%3BDoroshow%2C+James%3BHamilton%2C+Anne%3BMulkerin%2C+Daniel%3BGraham%2C+Martin%3BLockwood%2C+Graham+F%3BIvy%2C+Percy%3BEgorin%2C+Merrill%3BSchuler%2C+Barbara%3BGreenslade%2C+Denis%3BGoetz%2C+Andrew%3BKnight%2C+Ronald%3BThomas%2C+Rebecca%3BMonahan%2C+Brian+P%3BDahut%2C+William%3BGrem%2C+Jean+L%3BNational+Cancer+Institute+Organ+Dysfunction+Working+Group+Study&rft.aulast=Takimoto&rft.aufirst=Chris&rft.date=2003-07-15&rft.volume=21&rft.issue=14&rft.spage=2664&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 - 2003-08-14 N1 - Date created - 2003-07-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 2003 Jul 15;21(14):2633-5 [12860937] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rabbit antithymocyte globulin induction and sirolimus monotherapy supports prolonged islet allograft function in a nonhuman primate islet transplantation model. AN - 73422621; 12865786 AB - We reported that rabbit anti-thymocyte globulin (RATG) induction followed by maintenance immunosuppression with sirolimus supports human kidney allograft survival and asked if this combination would promote islet allograft survival in our primate model. Using intra-arterial streptozotocin infusion, we rendered four cynomolgus primates diabetic with undetectable C-peptide levels. Animals were maintained on insulin therapy for at least 1 month, and then islets from mixed lymphocyte reaction mismatched primates were infused into the portal vein. Immediately before the islet allotransplant and for 6 additional days, primates were infused with RATG (20 mg/kg) and given a sirolimus dose to achieve a 24-hr trough level of 8 to 14 ng/mL. The regimen resulted in profound peripheral and lymph node lymphocyte depletion for up to 1 month. Repopulation was gradual thereafter. One primate remained insulin-independent for 169 days and rejected after a sirolimus-dose reduction. Two primates died on day 23 while insulin independent because of wound dehiscence, and a third died on day 30 with high sirolimus levels. Liver sections revealed well-vascularized islets with no signs of inflammation. Using a nonhuman primate islet transplant model, RATG plus sirolimus supports islet survival as long as proper sirolimus levels are maintained, but the therapy is limited by sirolimus toxicity. Our findings suggest that RATG is not toxic for islets and thus may be considered in future clinical trails while recognizing that sirolimus monotherapy, with its difficult-to-achieve therapeutic dosing, may not be sufficient to maintain long-term islet allograft function in an autoimmune environment. JF - Transplantation AU - Hirshberg, Boaz AU - Preston, Edwin H AU - Xu, He AU - Tal, Michel G AU - Neeman, Ziv AU - Bunnell, David AU - Soleimanpour, Scott AU - Hale, Douglas A AU - Kirk, Allan D AU - Harlan, David M AD - NIDDK Transplantation and Autoimmunity Branch, National Institute Health, Bethesda, MD 20892, USA. BoazH@Intra.niddk.nih.gov. Y1 - 2003/07/15/ PY - 2003 DA - 2003 Jul 15 SP - 55 EP - 60 VL - 76 IS - 1 SN - 0041-1337, 0041-1337 KW - Antilymphocyte Serum KW - 0 KW - Immunosuppressive Agents KW - Insulin KW - Sirolimus KW - W36ZG6FT64 KW - Index Medicus KW - Models, Animal KW - Insulin -- analysis KW - Animals KW - Macaca fascicularis KW - Islets of Langerhans -- cytology KW - Rabbits KW - Transplantation, Homologous KW - Time Factors KW - Immunohistochemistry KW - Lymphocyte Count KW - Islets of Langerhans Transplantation -- immunology KW - Graft Survival -- physiology KW - Sirolimus -- therapeutic use KW - Islets of Langerhans Transplantation -- physiology KW - Immunosuppressive Agents -- therapeutic use KW - Antilymphocyte Serum -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73422621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transplantation&rft.atitle=Rabbit+antithymocyte+globulin+induction+and+sirolimus+monotherapy+supports+prolonged+islet+allograft+function+in+a+nonhuman+primate+islet+transplantation+model.&rft.au=Hirshberg%2C+Boaz%3BPreston%2C+Edwin+H%3BXu%2C+He%3BTal%2C+Michel+G%3BNeeman%2C+Ziv%3BBunnell%2C+David%3BSoleimanpour%2C+Scott%3BHale%2C+Douglas+A%3BKirk%2C+Allan+D%3BHarlan%2C+David+M&rft.aulast=Hirshberg&rft.aufirst=Boaz&rft.date=2003-07-15&rft.volume=76&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Transplantation&rft.issn=00411337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-04 N1 - Date created - 2003-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The importance of the nine-amino acid C-terminal sequence of exendin-4 for binding to the GLP-1 receptor and for biological activity. AN - 73421428; 12832104 AB - Exendin-4, a 39-amino acid (AA) peptide, is a long-acting agonist at the glucagon-like peptide-1 (GLP-1) receptor. Consequently, it may be preferable to GLP-1 as a long-term treatment for type 2 diabetes mellitus. Exendin-4 (Ex-4), unlike GLP-1, is not degraded by dipeptidyl peptidase IV (DPP IV), is less susceptible to degradation by neutral endopeptidase, and possesses a nine-AA C-terminal sequence absent from GLP-1. Here we examine the importance of these nine AAs for biological activity of Ex-4, a sequence of truncated Ex-4 analogs, and native GLP-1 and GLP-1 analogs to which all or parts of the C-terminal sequence have been added. We found that removing these AAs from Ex-4 to produce Ex (1-30) reduced the affinity for the GLP-1 receptor (GLP-1R) relative to Ex-4 (IC50: Ex-4, 3.22+/-0.9 nM; Ex (1-30), 32+/-5.8 nM) but made it comparable to that of GLP-1 (IC50: 44.9+/-3.2 nM). The addition of this nine-AA sequence to GLP-1 improved the affinity of both GLP-1 and the DPP IV resistant analog GLP-1 8-glycine for the GLP-1 receptor (IC50: GLP-1 Gly8 [GG], 220+/-23 nM; GLP-1 Gly8 Ex (31-39), 74+/-11 nM). Observations of the cAMP response in an insulinoma cell line show a similar trend for biological activity. JF - Regulatory peptides AU - Doyle, Máire E AU - Theodorakis, Michael J AU - Holloway, Harold W AU - Bernier, Michel AU - Greig, Nigel H AU - Egan, Josephine M AD - Diabetes Section, #23, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003/07/15/ PY - 2003 DA - 2003 Jul 15 SP - 153 EP - 158 VL - 114 IS - 2-3 SN - 0167-0115, 0167-0115 KW - Glucagon-Like Peptide-1 Receptor KW - 0 KW - Insulin KW - Peptides KW - Receptors, Glucagon KW - Venoms KW - exenatide KW - 9P1872D4OL KW - Index Medicus KW - Animals KW - Binding, Competitive KW - Molecular Sequence Data KW - CHO Cells KW - Insulin -- secretion KW - Amino Acid Sequence KW - Cell Line KW - Cricetinae KW - Peptides -- metabolism KW - Peptides -- chemistry KW - Venoms -- metabolism KW - Venoms -- chemistry KW - Peptides -- physiology KW - Receptors, Glucagon -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73421428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+peptides&rft.atitle=The+importance+of+the+nine-amino+acid+C-terminal+sequence+of+exendin-4+for+binding+to+the+GLP-1+receptor+and+for+biological+activity.&rft.au=Doyle%2C+M%C3%A1ire+E%3BTheodorakis%2C+Michael+J%3BHolloway%2C+Harold+W%3BBernier%2C+Michel%3BGreig%2C+Nigel+H%3BEgan%2C+Josephine+M&rft.aulast=Doyle&rft.aufirst=M%C3%A1ire&rft.date=2003-07-15&rft.volume=114&rft.issue=2-3&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Regulatory+peptides&rft.issn=01670115&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-07 N1 - Date created - 2003-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prematurity Is the Major Risk Factor for Late-Onset Group B Streptococcus Disease AN - 18871779; 5716141 AB - A case-control study was conducted in the greater Houston area to determine risk factors for late-onset group B streptococcus (GBS) disease (onset of disease or first positive culture between 7 and 180 days after birth). Characteristics of 122 case patients diagnosed during 1995-2000 were compared with control subjects matched for birth hospital and date of birth. Half the case patients were preterm infants, 84% of whom were born at <34 weeks of gestation. The risk for late-onset GBS disease increased by a factor of 1.34 (95% confidence interval [CI], 1.15-1.56) for each week of decreasing gestation, by 3.70 (95% CI, 1.35-10.1) for infants of black mothers, and by 4.15 (95% CI, 1.27-13.60) for infants of mothers with a positive GBS screening. These risk factors are similar to that of early-onset GBS disease. However, prematurity is the major risk factor for late-onset GBS disease. JF - Journal of Infectious Diseases AU - Lin, F-YC AU - Weisman, LE AU - Troendle, J AU - Adams, K AD - National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA Y1 - 2003/07/15/ PY - 2003 DA - 2003 Jul 15 SP - 267 EP - 271 VL - 188 IS - 2 SN - 0022-1899, 0022-1899 KW - man KW - streptococci KW - Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18871779?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Prematurity+Is+the+Major+Risk+Factor+for+Late-Onset+Group+B+Streptococcus+Disease&rft.au=Lin%2C+F-YC%3BWeisman%2C+LE%3BTroendle%2C+J%3BAdams%2C+K&rft.aulast=Lin&rft.aufirst=F-YC&rft.date=2003-07-15&rft.volume=188&rft.issue=2&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Expression of potential beta -catenin targets, cyclin D1, c-Jun, c-Myc, E-cadherin, and EGFR in chemically induced hepatocellular neoplasms from B6C3F1 mice AN - 18822494; 5714529 AB - In this study we used liver neoplasms induced by several chemical carcinogens to investigate potential nuclear targets associated with beta -catenin/Wnt signaling and potential membrane-associated beta -catenin binding partners. Strong expression of cyclin D1, in a pattern similar to that observed previously for beta -catenin, was observed by Western analysis for all five hepatoblastomas examined regardless of treatment. Increased expression of cyclin D1 was also detected in 12 of 35 (34%) hepatocellular neoplasms. Ten of 15 tumors (67%) that had mutations in the Catnb gene had upregulation of cyclin D1, while only 2 of 20 tumors (10%) without Catnb mutations had increased cyclin D1 expression. Immunohistochemical analysis confirmed strong expression of cyclin D1 in most nuclei of hepatoblastomas and scattered nuclear staining in hepatocellular tumors that had Catnb mutations. Increased c-Jun expression was observed in 19 of 30 (63%) hepatocellular tumors and all hepatoblastomas, although upregulation was not completely correlated with Catnb mutation. C-Myc expression was not increased in the tumors. Reduced expression of E-cadherin, which interacts with beta -catenin at the membrane, was observed in some tumors, but this did not correlate with Catnb mutation. Expression of the epidermal growth factor receptor, which may have a role in beta -catenin tyrosine phosphorylation, was lower in some tumors than in normal tissue depending on chemical treatment. The results provide evidence that increased expression of cyclin D1 and c-Jun may provide an advantage during tumor progression and in the transition from hepatocellular neoplasms to hepatoblastomas. Moreover, it is likely increased cyclin D1 expression results at least in part from Catnb mutation, beta -catenin accumulation, and increased Wnt signaling. JF - Toxicology and Applied Pharmacology AU - Anna, CH AU - Iida, M AU - Sills, R C AU - Devereux, T R AD - Laboratory of Molecular Carcinogenesis NIEHS, NIH, Research Triangle Park, NC 27709, USA, devereux@niehs.nih.gov Y1 - 2003/07/15/ PY - 2003 DA - 2003 Jul 15 SP - 135 EP - 145 PB - Elsevier Science (USA) VL - 190 IS - 2 SN - 0041-008X, 0041-008X KW - beta -Catenin KW - binding KW - cyclin D1 KW - mice KW - targets KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18822494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Expression+of+potential+beta+-catenin+targets%2C+cyclin+D1%2C+c-Jun%2C+c-Myc%2C+E-cadherin%2C+and+EGFR+in+chemically+induced+hepatocellular+neoplasms+from+B6C3F1+mice&rft.au=Anna%2C+CH%3BIida%2C+M%3BSills%2C+R+C%3BDevereux%2C+T+R&rft.aulast=Anna&rft.aufirst=CH&rft.date=2003-07-15&rft.volume=190&rft.issue=2&rft.spage=135&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1016%2FS0041-008X%2803%2900170-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0041-008X(03)00170-4 ER - TY - JOUR T1 - Gene modulation by the cyclooxygenase inhibitor, sulindac sulfide, in human colorectal carcinoma cells: possible link to apoptosis. AN - 73438077; 12734198 AB - The mechanisms underlying the anti-tumorigenic properties of cyclooxygenase inhibitors are not well understood. One novel hypothesis is alterations in gene expression. To test this hypothesis sulindac sulfide, which is used to treat familial adenomatous polyposis, was selected to detect gene modulation in human colorectal cells at physiological concentrations with microarray analysis. At micromolar concentrations, sulindac sulfide stimulated apoptosis and inhibited the growth of colorectal cancer cells on soft agar. Sulindac sulfide (10 microm) altered the expression of 65 genes in SW-480 colorectal cancer cells, which express cyclooxygenase-1 but little cyclooxygenase-2. A more detailed study of 11 genes revealed that their expression was altered in a time- and dose-dependent manner as measured by real-time RT-PCR. Northern analysis confirmed the expression of 9 of these genes, and Western analysis supported the conclusion that sulindac sulfide altered the expression of these proteins. Cyclooxygenase-deficient HCT-116 cells were more responsive to sulindac sulfide-induced gene expression than SW-480 cells. However, this response was diminished in HCT-116 cells overexpressing cyclooxygenase-1 compared with normal HCT-116 cells suggesting the presence of cyclooxygenase attenuates this response. However, prostaglandin E2, the main product of cyclooxygenase, only suppressed the sulindac sulfide-induced expression of two genes, with little known biological function while it modulated the expression of two more. The most likely explanation for this finding is the metabolism of sulindac sulfide to inactive metabolites by the peroxidase activity of cyclooxygenase. In conclusion, this is the first report showing sulindac sulfide, independent of cyclooxygenase, altered the expression of several genes possibly linked to its anti-tumorigenic and pro-apoptotic activity. JF - The Journal of biological chemistry AU - Bottone, Frank G AU - Martinez, Jeanelle M AU - Collins, Jennifer B AU - Afshari, Cynthia A AU - Eling, Thomas E AD - Laboratory of Molecular Carcinogenesis, the Laboratory of Computational Biology and Risk Analysis, and National Center for Toxicogenomics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/07/11/ PY - 2003 DA - 2003 Jul 11 SP - 25790 EP - 25801 VL - 278 IS - 28 SN - 0021-9258, 0021-9258 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cyclooxygenase Inhibitors KW - Isoenzymes KW - Membrane Proteins KW - RNA, Messenger KW - Sulindac KW - 184SNS8VUH KW - sulindac sulfide KW - 6UVA8S2DEY KW - DNA KW - 9007-49-2 KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - PTGS1 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Dinoprostone KW - K7Q1JQR04M KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Blotting, Northern KW - Apoptosis KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Transcription, Genetic KW - Cell Separation KW - Indomethacin -- pharmacology KW - Tumor Cells, Cultured KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Isoenzymes -- biosynthesis KW - Flow Cytometry KW - Time Factors KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology KW - Dose-Response Relationship, Drug KW - DNA -- metabolism KW - Cell Division -- drug effects KW - Reverse Transcriptase Polymerase Chain Reaction KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Cloning, Molecular KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Dinoprostone -- metabolism KW - Sulindac -- pharmacology KW - Sulindac -- analogs & derivatives KW - Colorectal Neoplasms -- enzymology KW - Colorectal Neoplasms -- drug therapy KW - Cyclooxygenase Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73438077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+modulation+by+the+cyclooxygenase+inhibitor%2C+sulindac+sulfide%2C+in+human+colorectal+carcinoma+cells%3A+possible+link+to+apoptosis.&rft.au=Bottone%2C+Frank+G%3BMartinez%2C+Jeanelle+M%3BCollins%2C+Jennifer+B%3BAfshari%2C+Cynthia+A%3BEling%2C+Thomas+E&rft.aulast=Bottone&rft.aufirst=Frank&rft.date=2003-07-11&rft.volume=278&rft.issue=28&rft.spage=25790&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 - 2003-08-14 N1 - Date created - 2003-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of insulin inhibition of transactivation by a C-terminal fragment of the forkhead transcription factor Foxo1 in rat hepatoma cells. AN - 73422103; 12724332 AB - The transcription factor Foxo1 controls the expression of genes involved in fundamental cellular processes. In keeping with its important physiological roles, Foxo1 activity is negatively regulated in response to growth factors and cytokines that activate a phosphatidylinositol 3-kinase (PI 3-kinase) protein kinase B (PKB)/Akt pathway. PKB/Akt-mediated phosphorylation of Foxo1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo1 from the nucleus, which is generally believed to explain the subsequent decrease of transcription. In the present study, using a chimeric protein in which a C-terminal fragment of Foxo1 (amino acids 208-652) containing the transactivation domain is fused to the yeast Gal4 DNA binding domain, we present evidence showing that insulin can directly regulate transactivation by Foxo1 in H4IIE rat hepatoma cells. Insulin inhibition of Foxo1-(208-652)-stimulated transactivation is mediated by PI 3-kinase but in contrast to full-length Foxo1, does not require either of the two PKB/Akt phosphorylation sites (Ser253 and Ser316) present in the protein fragment. Using mutational and deletion studies, we identify two potential phosphorylation sites, Ser319 and Ser499, as well as a 15-amino acid region located between residues 350 and 364 that are critical for insulin inhibition of transactivation by Foxo1-(208-652). We conclude that the transcriptional activity of Foxo1 is regulated at different levels by insulin: transactivation, as well as DNA binding and nuclear exclusion. These different regulatory mechanisms allow the precise control of transcription of Foxo1 target genes by insulin. JF - The Journal of biological chemistry AU - Perrot, Valerie AU - Rechler, Matthew M AD - Growth and Development Section, Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/07/11/ PY - 2003 DA - 2003 Jul 11 SP - 26111 EP - 26119 VL - 278 IS - 28 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Forkhead Transcription Factors KW - Foxo1a protein, rat KW - Insulin KW - Transcription Factors KW - Serine KW - 452VLY9402 KW - DNA KW - 9007-49-2 KW - Luciferases KW - EC 1.13.12.- KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Animals KW - Serine -- metabolism KW - Microscopy, Fluorescence KW - Mutagenesis, Site-Directed KW - Rats KW - Gene Expression Regulation, Enzymologic KW - Tumor Cells, Cultured KW - Phosphorylation KW - Molecular Sequence Data KW - Active Transport, Cell Nucleus KW - Plasmids -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Dose-Response Relationship, Drug KW - DNA Mutational Analysis KW - DNA -- metabolism KW - Luciferases -- metabolism KW - Amino Acid Sequence KW - Precipitin Tests KW - Protein Binding KW - Serine -- chemistry KW - Gene Deletion KW - Blotting, Western KW - beta-Galactosidase -- metabolism KW - Transfection KW - Models, Genetic KW - Protein Structure, Tertiary KW - Mutation KW - Cell Line KW - Transcription Factors -- metabolism KW - Insulin -- metabolism KW - Insulin -- pharmacology KW - Transcriptional Activation KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73422103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+insulin+inhibition+of+transactivation+by+a+C-terminal+fragment+of+the+forkhead+transcription+factor+Foxo1+in+rat+hepatoma+cells.&rft.au=Perrot%2C+Valerie%3BRechler%2C+Matthew+M&rft.aulast=Perrot&rft.aufirst=Valerie&rft.date=2003-07-11&rft.volume=278&rft.issue=28&rft.spage=26111&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 - 2003-08-14 N1 - Date created - 2003-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of Escherichia coli RNA Polymerase with the Ribosomal Protein S1 and the Sm-like ATPase Hfq AN - 18812646; 5701982 AB - We report evidence that ribosomal protein S1 and nucleic acid-binding protein Hfq copurify in molar ratios with RNA polymerase (RNAP). Purified S1 associates independently with RNAP, and Hfq binding to polymerase occurs in the presence of S1. Looking for a functional role of the RNAP-S1-Hfq association, we studied the effects of S1 and Hfq on transcription and coupled transcription-translation. S1 was capable of significant stimulation of the RNAP transcriptional activity from a number of promoters; the stimulatory effect was observed on linear as well as supercoiled DNA templates. In addition, we present biochemical and genetic evidence of ATPase activity associated with the Sm-like hexameric nucleic acid-binding protein Hfq. The limited sequence homology between Hfq and known ATP-utilizing enzymes suggests a new class of ATPases. JF - Biochemistry (Washington) AU - Sukhodolets, M V AU - Garges, S AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2003/07/08/ PY - 2003 DA - 2003 Jul 08 SP - 8022 EP - 8034 VL - 42 IS - 26 SN - 0006-2960, 0006-2960 KW - Hfq protein KW - ribosomal protein S1 KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18812646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Interaction+of+Escherichia+coli+RNA+Polymerase+with+the+Ribosomal+Protein+S1+and+the+Sm-like+ATPase+Hfq&rft.au=Sukhodolets%2C+M+V%3BGarges%2C+S&rft.aulast=Sukhodolets&rft.aufirst=M&rft.date=2003-07-08&rft.volume=42&rft.issue=26&rft.spage=8022&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi020638i LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1021/bi020638i ER - TY - JOUR T1 - Genomic transcriptional profiling of the developmental cycle of Chlamydia trachomatis AN - 18795829; 5667478 AB - Chlamydia trachomatis is one of the most common bacterial pathogens and is the etiological agent of debilitating sexually transmitted and ocular diseases in humans. The organism is an obligate intracellular prokaryote characterized by a highly specialized biphasic developmental cycle. We have performed genomic transcriptional analysis of the chlamydial developmental cycle. This approach has led to the identification of a small subset of genes that control the primary (immediate-early genes) and secondary (late genes) differentiation stages of the cycle. Immediate-early gene products initiate bacterial metabolism and potentially modify the bacterial phagosome to escape fusion with lysosomes. One immediate early gene (CT147) is a homolog of the human early endosomal antigen-1 that is localized to the chlamydial phagosome; suggesting a functional role for CT147 in establishing the parasitophorous vacuole in a nonfusogenic pathway. Late gene products terminate bacterial cell division and constitute structural components and remodeling activities involved in the formation of the highly disulfide cross-linked outer-membrane complex that functions in attachment and invasion of new host cells. Many of the genes expressed during the immediate-early and late differentiation stages are Chlamydia-specific and have evolutionary origins in eukaryotic lineages. JF - Proceedings of the National Academy of Sciences, USA AU - Belland, R J AU - Zhong, G AU - Crane, D D AU - Hogan, D AU - Sturdevant, D AU - Sharma, J AU - Beatty, W L AU - Caldwell, H D AD - Laboratories of Human Bacterial Pathogenesis and Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, MT 59840, rbelland@niaid.nih.gov Y1 - 2003/07/08/ PY - 2003 DA - 2003 Jul 08 SP - 8478 EP - 8483 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 14 SN - 0027-8424, 0027-8424 KW - CT147 gene KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02726:RNA and ribosomes KW - N 14550:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18795829?accountid=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=Genomic+transcriptional+profiling+of+the+developmental+cycle+of+Chlamydia+trachomatis&rft.au=Belland%2C+R+J%3BZhong%2C+G%3BCrane%2C+D+D%3BHogan%2C+D%3BSturdevant%2C+D%3BSharma%2C+J%3BBeatty%2C+W+L%3BCaldwell%2C+H+D&rft.aulast=Belland&rft.aufirst=R&rft.date=2003-07-08&rft.volume=100&rft.issue=14&rft.spage=8478&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.1331135100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.1331135100 ER - TY - JOUR T1 - Towards the delineation of the ancestral eutherian genome organization; comparative genome maps of human and the African elephant (Loxodonta africana) generated by chromosome painting AN - 1416690746; 2013-059901 AB - This study presents a whole-genome comparison of human and a representative of the Afrotherian clade, the African elephant, generated by reciprocal Zoo-FISH. An analysis of Afrotheria genomes is of special interest, because recent DNA sequence comparisons identify them as the oldest placental mammalian clade. Complete sets of whole-chromosome specific painting probes for the African elephant and human were constructed by degenerate oligonucleotide-primed PCR amplification of flow-sorted chromosomes. Comparative genome maps are presented based on their hybridization patterns. These maps show that the elephant has a moderately rearranged chromosome complement when compared to humans. The human paint probes identified 53 evolutionary conserved segments on the 27 autosomal elephant chromosomes and the X chromosome. Reciprocal experiments with elephant probes delineated 68 conserved segments in the human genome. The comparison with a recent aardvark and elephant Zoo-FISH study delineates new chromosomal traits which link the two Afrotherian species phylogenetically. In the absence of any morphological evidence the chromosome painting data offer the first non-DNA sequence support for an Afrotherian clade. The comparative human and elephant genome maps provide new insights into the karyotype organization of the proto-afrotherian, the ancestor of extant placental mammals, which most probably consisted of 2n = 46 chromosomes. JF - Proceedings - Royal Society of London, Biological Sciences AU - Froenicke, Lutz AU - Wienberg, Johannes AU - Stone, Gary AU - Adams, Lisa AU - Stanyon, Roscoe Y1 - 2003/07/07/ PY - 2003 DA - 2003 Jul 07 SP - 1331 EP - 1340 PB - Royal Society of London, London VL - 270 IS - 1522 SN - 0962-8452, 0962-8452 KW - Chordata KW - phylogeny KW - Loxodonta africana KW - Mammalia KW - Homo KW - Proboscidea KW - Primates KW - Hominidae KW - Elephantoidea KW - Theria KW - Homo sapiens sapiens KW - nucleic acids KW - Homo sapiens KW - DNA KW - Elephantidae KW - Vertebrata KW - Eutheria KW - Tetrapoda KW - Afrotheria KW - 11:Vertebrate paleontology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1416690746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+-+Royal+Society+of+London%2C+Biological+Sciences&rft.atitle=Towards+the+delineation+of+the+ancestral+eutherian+genome+organization%3B+comparative+genome+maps+of+human+and+the+African+elephant+%28Loxodonta+africana%29+generated+by+chromosome+painting&rft.au=Froenicke%2C+Lutz%3BWienberg%2C+Johannes%3BStone%2C+Gary%3BAdams%2C+Lisa%3BStanyon%2C+Roscoe&rft.aulast=Froenicke&rft.aufirst=Lutz&rft.date=2003-07-07&rft.volume=270&rft.issue=1522&rft.spage=1331&rft.isbn=&rft.btitle=&rft.title=Proceedings+-+Royal+Society+of+London%2C+Biological+Sciences&rft.issn=09628452&rft_id=info:doi/10.1098%2Frspb.2003.2383 L2 - http://rspb.royalsocietypublishing.org/ LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2013, American Geosciences Institute. Reference includes data supplied by the Royal Society, London, United Kingdom N1 - Date revised - 2013-01-01 N1 - Number of references - 55 N1 - Document feature - illus. incl. 1 table N1 - Last updated - 2013-08-02 N1 - CODEN - PRLBA4 N1 - SubjectsTermNotLitGenreText - Afrotheria; Chordata; DNA; Elephantidae; Elephantoidea; Eutheria; Hominidae; Homo; Homo sapiens; Homo sapiens sapiens; Loxodonta africana; Mammalia; nucleic acids; phylogeny; Primates; Proboscidea; Tetrapoda; Theria; Vertebrata DO - http://dx.doi.org/10.1098/rspb.2003.2383 ER - TY - JOUR T1 - Solution Structure of the Phosphoryl Transfer Complex between the Signal-transducing Protein IIA super(Glucose) and the Cytoplasmic Domain of the Glucose Transporter IICB super(Glucose) of the Escherichia coli Glucose Phosphotransferase System AN - 18787094; 5652561 AB - The solution structure of the final phosphoryl transfer complex in the glucose-specific arm of the Escherichia coli phosphotransferase system, between enzyme IIA super(Glucose) (IIA super(Glc)) and the cytoplasmic B domain (IIB super(Glc)) of the glucose transporter IICB super(Glc), has been solved by NMR. The interface ( similar to 1200-Aa super(2) buried surface) is formed by the interaction of a concave depression on IIA super(Glc) with a convex protrusion on IIB super(Glc). The phosphoryl donor and acceptor residues, His-90 of IIA super(Glc) and Cys-35 of IIB super(Glc) (residues of IIB super(Glc) are denoted in italics) are in close proximity and buried at the center of the interface. Cys-35 is primed for nucleophilic attack on the phosphorus atom by stabilization of the thiolate anion (pK sub(a) similar to 6.5) through intramolecular hydrogen bonding interactions with several adjacent backbone amide groups. Hydrophobic intermolecular contacts are supplemented by peripheral electrostatic interactions involving an alternating distribution of positively and negatively charged residues on the interaction surfaces of both proteins. Salt bridges between the Asp-38/Asp-94 pair of IIA super(Glc) and the Arg-38/Arg-40 pair of IIB super(Glc) neutralize the accumulation of negative charge in the vicinity of both the S gamma atom of Cys-35 and the phosphoryl group in the complex. A pentacoordinate phosphoryl transition state is readily accommodated without any change in backbone conformation, and the structure of the complex accounts for the preferred directionality of phosphoryl transfer between IIA super(Glc) and IIB super(Glc). The structures of IIA super(Glc) super(.)IIB super(Glc) and the two upstream complexes of the glucose phosphotransferase system (EI super(.)HPr and IIA super(Glc) super(.)HPr) reveal a cascade in which highly overlapping binding sites on HPr and IIA super(Glc) recognize structurally diverse proteins. JF - Journal of Biological Chemistry AU - Cai, M AU - Williams, DC Jr AU - Wang, G AU - Lee, B R AU - Peterkofsky, A AU - Clore, G M AD - Laboratory of Chemical Physics, NIDDK, Laboratory of Cell Biology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, mariusc@intra.niddk.nih.gov Y1 - 2003/07/04/ PY - 2003 DA - 2003 Jul 04 SP - 25191 EP - 25206 VL - 278 IS - 27 SN - 0021-9258, 0021-9258 KW - IIA glucose protein KW - IICB glucose protein KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18787094?accountid=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=Solution+Structure+of+the+Phosphoryl+Transfer+Complex+between+the+Signal-transducing+Protein+IIA+super%28Glucose%29+and+the+Cytoplasmic+Domain+of+the+Glucose+Transporter+IICB+super%28Glucose%29+of+the+Escherichia+coli+Glucose+Phosphotransferase+System&rft.au=Cai%2C+M%3BWilliams%2C+DC+Jr%3BWang%2C+G%3BLee%2C+B+R%3BPeterkofsky%2C+A%3BClore%2C+G+M&rft.aulast=Cai&rft.aufirst=M&rft.date=2003-07-04&rft.volume=278&rft.issue=27&rft.spage=25191&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M302677200 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1074/jbc.M302677200 ER - TY - JOUR T1 - Treatment of ANCA-associated vasculitis. AN - 73426763; 12840085 JF - The New England journal of medicine AU - Langford, Carol A AD - Immunologic Diseases Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md, USA. Y1 - 2003/07/03/ PY - 2003 DA - 2003 Jul 03 SP - 3 EP - 4 VL - 349 IS - 1 KW - Antibodies, Antineutrophil Cytoplasmic KW - 0 KW - Immunosuppressive Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - Azathioprine KW - MRK240IY2L KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Recurrence KW - Cyclophosphamide -- therapeutic use KW - Azathioprine -- therapeutic use KW - Vasculitis -- drug therapy KW - Vasculitis -- immunology KW - Immunosuppressive Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73426763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Treatment+of+ANCA-associated+vasculitis.&rft.au=Langford%2C+Carol+A&rft.aulast=Langford&rft.aufirst=Carol&rft.date=2003-07-03&rft.volume=349&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-08 N1 - Date created - 2003-07-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 2003 Nov 20;349(21):2072-3; author reply 2072-3 [14627795] Comment On: N Engl J Med. 2003 Jul 3;349(1):36-44 [12840090] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structure-activity relationship comparison of (S)-2beta-substituted 3alpha-(bis[4-fluorophenyl]methoxy)tropanes and (R)-2beta-substituted 3beta-(3,4-dichlorophenyl)tropanes at the dopamine transporter. AN - 73408237; 12825932 AB - Extensive structure-activity relationships at the dopamine transporter (DAT) have been developed around two classes of tropane-based ligands. Opposing stereoselectivity and divergent structural requirements for optimal DAT binding suggest that these tropane-based DAT inhibitors may not access identical binding domains. To further investigate this hypothesis, a series of (S)-2beta-carboalkoxy-3alpha-(bis[4-fluorophenyl]methoxy)tropanes (11a-f, 13-16) and their identically (R)-2beta-substituted 3beta-(3,4-dichlorophenyl)tropanes (3, 5a-d) were prepared and evaluated for binding at the DAT and for inhibition of [(3)H]dopamine uptake in rat brain. These studies showed that most of the identically 2-carboalkoxy-substituted analogues, within the two classes of compounds, bind with high affinity to DAT (K(i) = 5.5-100 nM), albeit with opposite stereochemistry. However, the larger azido- (15) and isothiocyanato- (16) (S)-2beta-carbophenylethoxy-3alpha-(bis[4-fluorophenyl]methoxy)tropanes demonstrated a significant decrease in DAT binding potency (IC(50) = 210 and 537 nM, respectively), suggesting that the DAT does not tolerate 2-position steric bulk in the benztropine class, as it does with the 2-substituted 3-aryltropanes. In addition, binding affinities at the serotonin transporter, norepinephrine transporter, and muscarinic receptors were evaluated and compared for compounds 2, 3, 11a-e, and 13. Together, the binding profiles across these systems demonstrated significant differences between these two classes of tropane-based ligands, which may be exploited toward the discovery of a cocaine-abuse pharmacotherapeutic. JF - Journal of medicinal chemistry AU - Zou, Mu-Fa AU - Kopajtic, Theresa AU - Katz, Jonathan L AU - Newman, Amy Hauck AD - Medicinal Chemistry and Psychobiology Sections, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA. Y1 - 2003/07/03/ PY - 2003 DA - 2003 Jul 03 SP - 2908 EP - 2916 VL - 46 IS - 14 SN - 0022-2623, 0022-2623 KW - Dopamine Plasma Membrane Transport Proteins KW - 0 KW - Ligands KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Slc6a3 protein, rat KW - Tropanes KW - Fluorine KW - 284SYP0193 KW - Chlorine KW - 4R7X1O2820 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Stereoisomerism KW - Models, Molecular KW - Brain -- metabolism KW - Fluorine -- chemistry KW - Radioligand Assay KW - Structure-Activity Relationship KW - Rats KW - Binding, Competitive KW - In Vitro Techniques KW - Brain -- ultrastructure KW - Chlorine -- chemistry KW - Synaptosomes -- metabolism KW - Tropanes -- pharmacology KW - Tropanes -- chemistry KW - Dopamine -- metabolism KW - Membrane Transport Proteins -- metabolism KW - Tropanes -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73408237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structure-activity+relationship+comparison+of+%28S%29-2beta-substituted+3alpha-%28bis%5B4-fluorophenyl%5Dmethoxy%29tropanes+and+%28R%29-2beta-substituted+3beta-%283%2C4-dichlorophenyl%29tropanes+at+the+dopamine+transporter.&rft.au=Zou%2C+Mu-Fa%3BKopajtic%2C+Theresa%3BKatz%2C+Jonathan+L%3BNewman%2C+Amy+Hauck&rft.aulast=Zou&rft.aufirst=Mu-Fa&rft.date=2003-07-03&rft.volume=46&rft.issue=14&rft.spage=2908&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 - 2003-08-07 N1 - Date created - 2003-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Zinc supplement use and risk of prostate cancer. AN - 73415451; 12837837 AB - The high concentration of zinc in the prostate suggests that zinc may play a role in prostate health. We examined the association between supplemental zinc intake and prostate cancer risk among 46 974 U.S. men participating in the Health Professionals Follow-Up Study. During 14 years of follow-up from 1986 through 2000, 2901 new cases of prostate cancer were ascertained, of which 434 cases were diagnosed as advanced cancer. Supplemental zinc intake at doses of up to 100 mg/day was not associated with prostate cancer risk. However, compared with nonusers, men who consumed more than 100 mg/day of supplemental zinc had a relative risk of advanced prostate cancer of 2.29 (95% confidence interval = 1.06 to 4.95; P(trend) =.003), and men who took supplemental zinc for 10 or more years had a relative risk of 2.37 (95% confidence interval = 1.42 to 3.95; P(trend)<.001). Although we cannot rule out residual confounding by supplemental calcium intake or some unmeasured correlate of zinc supplement use, our findings, that chronic zinc oversupply may play a role in prostate carcinogenesis, warrant further investigation. JF - Journal of the National Cancer Institute AU - Leitzmann, Michael F AU - Stampfer, Meir J AU - Wu, Kana AU - Colditz, Graham A AU - Willett, Walter C AU - Giovannucci, Edward L AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. leitzmann@mail.nih.gov Y1 - 2003/07/02/ PY - 2003 DA - 2003 Jul 02 SP - 1004 EP - 1007 VL - 95 IS - 13 KW - Carcinogens KW - 0 KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Health Personnel -- statistics & numerical data KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - United States -- epidemiology KW - Male KW - Risk Assessment KW - Prostatic Neoplasms -- metabolism KW - Zinc -- administration & dosage KW - Prostatic Neoplasms -- epidemiology KW - Carcinogens -- administration & dosage KW - Prostatic Neoplasms -- chemically induced KW - Prostatic Neoplasms -- prevention & control KW - Dietary Supplements KW - Zinc -- adverse effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73415451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Zinc+supplement+use+and+risk+of+prostate+cancer.&rft.au=Leitzmann%2C+Michael+F%3BStampfer%2C+Meir+J%3BWu%2C+Kana%3BColditz%2C+Graham+A%3BWillett%2C+Walter+C%3BGiovannucci%2C+Edward+L&rft.aulast=Leitzmann&rft.aufirst=Michael&rft.date=2003-07-02&rft.volume=95&rft.issue=13&rft.spage=1004&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=1460-2105&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-05 N1 - Date created - 2003-07-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 2003 Oct 15;95(20):1556; author reply 1556-7 [14559884] J Natl Cancer Inst. 2004 Jul 21;96(14):1108; author reply 1108-9 [15265974] J Natl Cancer Inst. 2004 Feb 4;96(3):239-40; author reply 240-1 [14759997] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitory attentional control in patients with frontal lobe damage. AN - 85374343; pmid-12821109 AB - The performance of a group of frontal lobe lesion and a group of frontal lobe dementia patients was compared with the performance of their respective matched normal control groups on two tests of inhibitory attentional control-the stop-signal reaction time task and a negative priming task. Both patient groups responded significantly slower than their respective normal control groups, but they showed only marginally significant selective impairments on the measures of inhibition. The data suggest that the specific inhibitory processes evaluated by these two tests are, in general, spared in patients with focal frontal lobe lesions or frontal lobe degeneration. JF - Brain and cognition AU - Dimitrov, Mariana AU - Nakic, Marina AU - Elpern-Waxman, Jordan AU - Granetz, Joy AU - O'Grady, Joy AU - Phipps, Michael AU - Milne, Elizabeth AU - Logan, Gordon D AU - Hasher, Lynn AU - Grafman, Jordan AD - Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bldg. 10, Room 5C205, 10 Center Drive, MSC 1440, Bethesda, MD 20892-1440, USA. Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 258 EP - 270 VL - 52 IS - 2 SN - 0278-2626, 0278-2626 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Atrophy: pathology KW - *Attention KW - Dementia: diagnosis KW - *Dementia: physiopathology KW - Female KW - Frontal Lobe: pathology KW - *Frontal Lobe: physiopathology KW - Humans KW - *Inhibition (Psychology) KW - Male KW - Middle Aged KW - Neuropsychological Tests UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85374343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+and+cognition&rft.atitle=Inhibitory+attentional+control+in+patients+with+frontal+lobe+damage.&rft.au=Dimitrov%2C+Mariana%3BNakic%2C+Marina%3BElpern-Waxman%2C+Jordan%3BGranetz%2C+Joy%3BO%27Grady%2C+Joy%3BPhipps%2C+Michael%3BMilne%2C+Elizabeth%3BLogan%2C+Gordon+D%3BHasher%2C+Lynn%3BGrafman%2C+Jordan&rft.aulast=Dimitrov&rft.aufirst=Mariana&rft.date=2003-07-01&rft.volume=52&rft.issue=2&rft.spage=258&rft.isbn=&rft.btitle=&rft.title=Brain+and+cognition&rft.issn=02782626&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - SuppNotes - Cites: Br J Psychiatry. 1996 Oct;169(4):416-22[8894190]; Cites: Brain Res. 1996 Jul 22;728(1):79-89[8864300]; Cites: J Am Acad Child Adolesc Psychiatry. 1997 Mar;36(3):374-83[9055518]; Cites: Br J Psychiatry. 1997 Jul;171:1-3[9328484]; Cites: Science. 1998 May 1;280(5364):747-9[9563953]; Cites: Behav Brain Res. 1998 Jul;94(1):33-43[9708837]; Cites: Fundam Clin Pharmacol. 1998;12(4):463-7[9711471]; Cites: Dev Psychol. 1998 Sep;34(5):956-69[9779742]; Cites: Dev Psychol. 1999 Jan;35(1):205-13[9923475]; Cites: Int J Psychophysiol. 1999 Mar;31(3):197-217[10076774]; Cites: Neuropsychologia. 1999 May;37(5):595-604[10340318]; Cites: Brain. 1999 May;122 ( Pt 5):981-91[10355680]; Cites: Rev Neurosci. 1999;10(1):49-57[10356991]; Cites: Am J Psychiatry. 1999 Jun;156(6):891-6[10360128]; Cites: Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8301-6[10393989]; Cites: Neuropsychologia. 1999 Aug;37(9):1005-27[10468365]; Cites: Nature. 1999 Nov 11;402(6758):179-81[10647008]; Cites: Neuropsychologia. 2000;38(4):363-79[10683388]; Cites: Neuropsychologia. 2000;38(5):701-11[10689046]; Cites: Psychophysiology. 2000 Mar;37(2):216-23[10731771]; Cites: Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8728-33[10900023]; Cites: Psychol Res. 2000;63(3-4):289-98[11004882]; Cites: J Clin Exp Neuropsychol. 1990 Aug;12(4):485-501[1698809]; Cites: Neuropsychologia. 1991;29(12):1241-9[1791934]; Cites: J Neurosci. 1991 Aug;11(8):2383-402[1869921]; Cites: Behav Brain Res. 1990 Dec 14;41(2):81-94[2288668]; Cites: Proc Natl Acad Sci U S A. 1990 Jan;87(1):256-9[2296583]; Cites: Neuropsychologia. 1989;27(4):495-503[2733822]; Cites: Brain Res. 1989 Aug 21;495(1):100-7[2776028]; Cites: Ciba Found Symp. 1987;132:187-200[3322715]; Cites: Arch Gen Psychiatry. 1988 Sep;45(9):814-21[3415424]; Cites: Neuropsychologia. 1987;25(2):359-65[3601041]; Cites: Hum Neurobiol. 1985;4(3):169-79[3934116]; Cites: Neurology. 1986 Feb;36(2):212-6[3945393]; Cites: Hum Neurobiol. 1985;4(3):137-42[4066424]; Cites: Ann Neurol. 1985 Nov;18(5):617-9[4073854]; Cites: Exp Neurol. 1973 Mar-Apr;39(2):204-14[4634005]; Cites: Philos Trans R Soc Lond B Biol Sci. 1982 Jun 25;298(1089):199-209[6125971]; Cites: Electroencephalogr Clin Neurophysiol. 1980 Oct;50(1-2):112-24[6159179]; Cites: J Exp Psychol Hum Percept Perform. 1984 Apr;10(2):276-91[6232345]; Cites: Biol Psychiatry. 1981 Nov;16(11):1085-100[7349622]; Cites: J Abnorm Child Psychol. 1995 Aug;23(4):411-37[7560554]; Cites: J Abnorm Child Psychol. 1995 Apr;23(2):235-66[7642836]; Cites: J Geriatr Psychiatry Neurol. 1995 Jan;8(1):42-8[7710647]; Cites: Neuropsychologia. 1995 Mar;33(3):341-52[7792000]; Cites: Neurology. 1994 Dec;44(12):2308-14[7991117]; Cites: Clin Neuropathol. 1994 May-Jun;13(3):109-16[8088029]; Cites: Psychol Aging. 1994 Mar;9(1):103-12[8185857]; Cites: Neuropsychologia. 1993 Sep;31(9):907-22[8232848]; Cites: J Exp Psychol Hum Percept Perform. 1993 Dec;19(6):1238-50[8294889]; Cites: Neuropsychologia. 1995 Oct;33(10):1243-53[8552227]; Cites: Ann N Y Acad Sci. 1995 Dec 15;769:151-9[8595022]; Cites: J Neural Transm Suppl. 1996;47:103-23[8841959]; Cites: J Neural Transm Suppl. 1996;47:125-32[8841960]; Cites: Neuropsychologia. 1996 Oct;34(10):953-63[8843061]; Cites: Prog Neurobiol. 1996 Nov;50(4):381-425[9004351] N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Language lateralization in a bimanual language. AN - 85286748; pmid-12965045 AB - Unlike spoken languages, sign languages of the deaf make use of two primary articulators, the right and left hands, to produce signs. This situation has no obvious parallel in spoken languages, in which speech articulation is carried out by symmetrical unitary midline vocal structures. This arrangement affords a unique opportunity to examine the robustness of linguistic systems that underlie language production in the face of contrasting articulatory demands and to chart the differential effects of handedness for highly skilled movements. Positron emission tomography (PET) technique was used to examine brain activation in 16 deaf users of American Sign Language (ASL) while subjects generated verb signs independently with their right dominant and left nondominant hands (compared to the repetition of noun signs). Nearly identical patterns of left inferior frontal and right cerebellum activity were observed. This pattern of activation during signing is consistent with patterns that have been reported for spoken languages including evidence for specializations of inferior frontal regions related to lexical-semantic processing, search and retrieval, and phonological encoding. These results indicate that lexical-semantic processing in production relies upon left-hemisphere regions regardless of the modality in which a language is realized, and that this left-hemisphere activation is stable, even in the face of conflicting articulatory demands. In addition, these data provide evidence for the role of the right posterolateral cerebellum in linguistic-cognitive processing and evidence of a left ventral fusiform contribution to sign language processing. JF - Journal of Cognitive Neuroscience AU - Corina, David P AU - San Jose-Robertson Lucila AU - Guillemin, Andre AU - High, Julia AU - Braun, Allen R AD - Virginia Merrill Bloedel Hearing Research Center, University of Washington; National Institute on Deafness and Other Communication Disorders PY - 2003 SP - 718 EP - 730 VL - 15 IS - 5 SN - 0898-929X, 0898-929X KW - Photic Stimulation KW - Brain Mapping KW - Comparative Study KW - Support, U.S. Gov't, P.H.S. KW - Verbal Behavior KW - Human KW - Adult KW - Brain KW - Tomography, Emission-Computed KW - Male KW - Female KW - Semantics KW - Hearing Impaired Persons KW - Language KW - Sign Language KW - Dominance, Cerebral UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85286748?accountid=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+Cognitive+Neuroscience&rft.atitle=Language+lateralization+in+a+bimanual+language.&rft.au=Corina%2C+David+P%3BSan+Jose-Robertson+Lucila%3BGuillemin%2C+Andre%3BHigh%2C+Julia%3BBraun%2C+Allen+R&rft.aulast=Corina&rft.aufirst=David&rft.date=2003-07-01&rft.volume=15&rft.issue=5&rft.spage=718&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cognitive+Neuroscience&rft.issn=0898929X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Antiviral and immunological benefits in HIV patients receiving intranasal peptide T (DAPTA). AN - 75707748; 14499289 AB - D-Ala-Peptide T-amide (DAPTA), the first viral entry inhibitor, blocks chemokine (CCR5) receptors, not CD4. Early investigators could not "replicate" DAPTAs potent in vitro antiviral effect using the lab-adapted, X4, peptide T-insensitive strain, IIIB, delaying clinical virological studies. We now report that DAPTA, administered to eleven long-term infected (mean=17 years) patients with stable persistent plasma "virus" for up to 32 weeks did not change this level. Infectious virus could not be isolated from their plasma suggesting HIV RNA was devoid of replicative capacity. Progressively less actual virus (P<0.01) could be isolated from white blood cells (PBMCs). DAPTA flushed the monocyte reservoir to undetectable viral levels in most patients. Five of eleven had a mean CD4 increase of 33%. Immune benefits also included a four-fold increase in gamma-interferon-secreting T-cells (antiviral cytotoxic T-cells) in the absence of drug-related toxicity. All five CD4 responders had increases in antiviral T cells and decreases in infected monocytes, an argument for initiating further studies promptly. JF - Peptides AU - Polianova, Maria T AU - Ruscetti, Francis W AU - Pert, Candace B AU - Tractenberg, Rochelle E AU - Leoung, Gifford AU - Strang, Scott AU - Ruff, Michael R AD - Leukocyte Biology Section, Center for Cancer Research, NCI-FCRDC, Frederick, MD 21702, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 1093 EP - 1098 VL - 24 IS - 7 SN - 0196-9781, 0196-9781 KW - Antigens, CD14 KW - 0 KW - Antiviral Agents KW - DNA, Viral KW - HIV Core Protein p24 KW - RNA, Viral KW - Peptide T KW - 106362-33-8 KW - Index Medicus KW - Neutrophils -- virology KW - Antiviral Agents -- therapeutic use KW - Coculture Techniques KW - Macrophages -- chemistry KW - CD8-Positive T-Lymphocytes -- drug effects KW - HIV-1 -- isolation & purification KW - Humans KW - CD8-Positive T-Lymphocytes -- chemistry KW - Macrophages -- virology KW - Monocytes -- virology KW - HIV Core Protein p24 -- analysis KW - CD4 Lymphocyte Count KW - Viral Load KW - Polymerase Chain Reaction KW - Neutrophils -- chemistry KW - DNA, Viral -- analysis KW - Administration, Intranasal KW - Antigens, CD14 -- analysis KW - Antiretroviral Therapy, Highly Active KW - Virus Integration -- drug effects KW - CD8-Positive T-Lymphocytes -- virology KW - Monocytes -- chemistry KW - HIV-1 -- drug effects KW - RNA, Viral -- blood KW - Peptide T -- pharmacology KW - Peptide T -- therapeutic use KW - HIV Infections -- virology KW - Virus Replication -- drug effects KW - HIV Infections -- immunology KW - HIV Infections -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75707748?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Peptides&rft.atitle=Antiviral+and+immunological+benefits+in+HIV+patients+receiving+intranasal+peptide+T+%28DAPTA%29.&rft.au=Polianova%2C+Maria+T%3BRuscetti%2C+Francis+W%3BPert%2C+Candace+B%3BTractenberg%2C+Rochelle+E%3BLeoung%2C+Gifford%3BStrang%2C+Scott%3BRuff%2C+Michael+R&rft.aulast=Polianova&rft.aufirst=Maria&rft.date=2003-07-01&rft.volume=24&rft.issue=7&rft.spage=1093&rft.isbn=&rft.btitle=&rft.title=Peptides&rft.issn=01969781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-06-21 N1 - Date created - 2003-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel small molecule cyclin-dependent kinases modulators in human clinical trials. AN - 75707030; 14508085 AB - Aberrations in cell cycle control occurs in the majority of human malignancies due to inactivation of tumor suppressor gene Rb by the phosphorylation induced by "hyperactive" cyclin-dependent kinases. Thus, it is quite reasonable to design cdk modulators for the prevention and treatment of human neoplasms. In order to target the cdk complexes, 2 main strategies were considered: to target the ATP binding site of cdks (direct cdk modulators) and to target upstream pathways required for cdk activation (indirect cdk modulators). Examples for the first group include flavopiridol, roscovitine, BMS-387032. Examples for the second group include perifosine, lovastatin, UCN-01. The first example of a direct small molecule cdk modulator tested in the clinic, flavopiridol, is a pan-cdk inhibitor that not only promotes cell cycle arrest but also halts transcriptional elongation, promotes apoptosis, induces differentiation and has antiangiogenic properties. Clinical trials with this agent were performed with at least 3 different schedules of administration: 1 hour infusion, 24 hour infusion and 72 hour infusion. Main toxicities for infusions >/=24 hours are secretory diarrhea and pro-inflammatory syndrome. In addition, patients receiving shorter infusions have nausea/vomiting and neutropenia. Some clinical responses were observed in several patients with refractory malignancies. Based on these encouraging results, a Phase 3 trial comparing standard combination chemotherapy versus combination chemotherapy plus flavopiridol is currently under investigation. The second example of direct small molecule cdk modulator tested in clinical trials is UCN-01 (7-hydroxi-staurosporine). UCN-01 has interesting preclinical features: inhibits ca2+-dependent PKCs, promotes apoptosis, arrest cell cycle progression at G1/S and abrogates checkpoints upon DNA damage. The first Phase I trial of UCN-01 demonstrated a very prolonged half-life. Based on this novel feature, UCN-01 is administered as a 72 hour continuous infusion every 4 weeks (second and subsequent cycles UCN-01 is administered as a 36-hour infusion). Other shorter schedules (i.e., 3 hours) are being tested. Dose-limiting toxicities include nausea/vomiting, hypoxemia and insulin-resistant hyperglycemia. Combination trials with cisplatin and other DNA-damaging agents are being tested. Recently, Phase I trials with two novel small molecule cdk modulators, BMS 387032 and R-Roscovitine (CYC202), have commenced with good tolerability. Phase 2 trials and Phase I trials in combination with standard chemotherapy is being planned with these agents. In summary, novel small molecule cdk modulators are being tested in the clinic with interesting results. Although these small molecules are directed towards a very prevalent cause of carcinogenesis, we need to test them in advanced clinical trials to determine the future of this class of agents for the prevention and therapy of human malignancies. JF - Cancer biology & therapy AU - Senderowicz, Adrian M AD - Molecular Therapeutics Unit, Oral and Pharyngeal Cancer Branch, National Institute of Craniofacial and Dental Research, Natonal Institute of Health, Bethesda, MD 20892-4330, USA. sendero@helix.nih.gov PY - 2003 SP - S84 EP - S95 VL - 2 IS - 4 Suppl 1 SN - 1538-4047, 1538-4047 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Retinoblastoma Protein KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Humans KW - Adenosine Triphosphate -- metabolism KW - Retinoblastoma Protein -- metabolism KW - Clinical Trials as Topic KW - Cell Division -- drug effects KW - Models, Chemical KW - Models, Biological KW - Antineoplastic Agents -- pharmacology KW - Cell Cycle -- drug effects KW - Binding Sites KW - Adenosine Triphosphate -- chemistry KW - Neoplasms -- drug therapy KW - Neoplasms -- enzymology KW - Enzyme Inhibitors -- pharmacology KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75707030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biology+%26+therapy&rft.atitle=Novel+small+molecule+cyclin-dependent+kinases+modulators+in+human+clinical+trials.&rft.au=Senderowicz%2C+Adrian+M&rft.aulast=Senderowicz&rft.aufirst=Adrian&rft.date=2003-07-01&rft.volume=2&rft.issue=4+Suppl+1&rft.spage=S84&rft.isbn=&rft.btitle=&rft.title=Cancer+biology+%26+therapy&rft.issn=15384047&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-17 N1 - Date created - 2003-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of arsenic induced cytotoxicity by tea. AN - 75706181; 14507244 AB - Arsenic, a naturally ocurring chemical element, is considered hazardous to human health. Inorganic arsenic compounds were found to induce cytotoxicity in Chinese hamster V-79 cells in culture. The arsenite form was more toxic than arsenate. Extracts of green and two varieties of black tea, as well as their principal polyphenols, (-)-epigallocatechingallate and theaflavin, efficiently counteracted the cytotoxic effects of arsenic compounds. On the basis of the amount of tea extract that afforded 50% protection to the cells from arsenic induced cytotoxicity, black tea was found to be as effective as green tea. The protective effect was attributable to the contents of not only (-)-epigallocatechingallate but also of theaflavin, the latter being a predominant polyphenol present in black tea. JF - Asian Pacific journal of cancer prevention : APJCP AU - Sinha, Dona AU - Roy, Madhumita AU - Dey, Subhabrata AU - Siddiqi, M AU - Bhattacharya, R K AD - Environmental Carcinogenesis and Toxicology Department, Chittaranjan National Cancer institute, Kolkata 700 026, India. PY - 2003 SP - 233 EP - 237 VL - 4 IS - 3 SN - 1513-7368, 1513-7368 KW - Cytotoxins KW - 0 KW - Tea KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Animals KW - Cricetulus KW - Cell Line, Tumor KW - Chemoprevention KW - Male KW - Cricetinae KW - Arsenic -- toxicity KW - Cytotoxins -- antagonists & inhibitors KW - Arsenic -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/75706181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.atitle=Modulation+of+arsenic+induced+cytotoxicity+by+tea.&rft.au=Sinha%2C+Dona%3BRoy%2C+Madhumita%3BDey%2C+Subhabrata%3BSiddiqi%2C+M%3BBhattacharya%2C+R+K&rft.aulast=Sinha&rft.aufirst=Dona&rft.date=2003-07-01&rft.volume=4&rft.issue=3&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Asian+Pacific+journal+of+cancer+prevention+%3A+APJCP&rft.issn=15137368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-24 N1 - Date created - 2003-09-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety of cisplatin after severe hypersensitivity reactions to carboplatin in patients with recurrent ovarian carcinoma. AN - 73577775; 12926091 AB - Carboplatin is a milestone drug against ovarian carcinoma; it is used both in front-line and second-line chemotherapy. Hypersensitivity reactions to carboplatin may occur during the treatment as salvage therapy. The purpose of this study was to describe the feasibility of the replacing of carboplatin with cisplatin in patients presenting with severe hypersensitivity reactions to carboplatin. Ten consecutive patients with platinum-sensitive, recurrent ovarian carcinoma, presenting with moderate/severe hypersensitivity reactions to carboplatin were treated with cisplatin 60 mg/m2 from January 2000 to December 2002. Hypersensitivity reactions consisted of respiratory distress (chest tightness, wheezing, dyspnea), urticaria/erythema with tachycardia, facial swelling and hypotension. The total number of cisplatin cycles given was 44 (range 2-5). The treatment with cisplatin was generally well tolerated. No serious allergic reactions occurred. A mild allergic reaction was recorded (urticaria) in only one case, after one cycle of cisplatin, and the patient was not rechallenged because of progressive disease. No reductions of chemotherapy doses were needed. To date, platinum-based regimens remain the most effective treatment in recurrent platinum-sensitive ovarian cancer with a high rate of objective responses. Although our experience is limited, we suggest that, under anesthesiologic surveillance and providing immunologic blockade, the replacement of carboplatin salvage therapy with cisplatin can be considered a safe therapeutic strategy in patients who cannot continue carboplatin due to allergic reactions. JF - Anticancer research AU - Ottaiano, A AU - Tambaro, R AU - Greggi, S AU - Prato, R AU - Di Maio, M AU - Esposito, G AU - Scala, F AU - Barletta, E AU - Losito, S AU - De Vivo, R AU - Iaffaioli, V R AU - Pignata, S AD - Division of Medical Oncology B, National Cancer Institute, G. Pascale Foundation, via M. Semmola, 80131, Naples, Italy. PY - 2003 SP - 3465 EP - 3468 VL - 23 IS - 4 SN - 0250-7005, 0250-7005 KW - Antineoplastic Agents KW - 0 KW - Carboplatin KW - BG3F62OND5 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Humans KW - Salvage Therapy KW - Aged KW - Middle Aged KW - Female KW - Cisplatin -- therapeutic use KW - Neoplasm Recurrence, Local -- immunology KW - Neoplasm Recurrence, Local -- drug therapy KW - Drug Hypersensitivity -- etiology KW - Carboplatin -- therapeutic use KW - Cisplatin -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Carboplatin -- adverse effects KW - Ovarian Neoplasms -- immunology KW - Ovarian Neoplasms -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73577775?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Safety+of+cisplatin+after+severe+hypersensitivity+reactions+to+carboplatin+in+patients+with+recurrent+ovarian+carcinoma.&rft.au=Ottaiano%2C+A%3BTambaro%2C+R%3BGreggi%2C+S%3BPrato%2C+R%3BDi+Maio%2C+M%3BEsposito%2C+G%3BScala%2C+F%3BBarletta%2C+E%3BLosito%2C+S%3BDe+Vivo%2C+R%3BIaffaioli%2C+V+R%3BPignata%2C+S&rft.aulast=Ottaiano&rft.aufirst=A&rft.date=2003-07-01&rft.volume=23&rft.issue=4&rft.spage=3465&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 - 2003-09-30 N1 - Date created - 2003-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. AN - 73574094; 12915819 AB - To evaluate the efficacy and safety of ganciclovir therapy in neonates with congenital cytomegalovirus (CMV) disease. Neonates with symptomatic CMV disease involving the central nervous system were randomly assigned to receive 6 weeks of intravenous ganciclovir versus no treatment. The primary end point was improved brainstem-evoked response (BSER) between baseline and 6-month follow-up (or, for patients with normal baseline hearing, normal BSER at both time points). From 1991 to 1999, 100 patients were enrolled. Of these, 42 patients had both a baseline and 6-month follow-up BSER audiometric examination and thus were evaluable for the primary end point. Twenty-one (84%) of 25 ganciclovir recipients had improved hearing or maintained normal hearing between baseline and 6 months versus 10 (59%) of 17 control patients (P=.06). None (0%) of 25 ganciclovir recipients had worsening in hearing between baseline and 6 months versus 7 (41%) of 17 control patients (P or =1 year versus 13 (68%) of 19 control patients (P<.01). A total of 89 patients had absolute neutrophil counts determined during the course of the study; 29 (63%) of 46 ganciclovir-treated patients had grade 3 or 4 neutropenia during treatment versus 9 (21%) of 43 control patients (P<.01). Ganciclovir therapy begun in the neonatal period in symptomatically infected infants with CMV infection involving the central nervous system prevents hearing deterioration at 6 months and may prevent hearing deterioration at > or =1 year. Almost two thirds of treated infants have significant neutropenia during therapy. JF - The Journal of pediatrics AU - Kimberlin, David W AU - Lin, Chin-Yu AU - Sánchez, Pablo J AU - Demmler, Gail J AU - Dankner, Wayne AU - Shelton, Mark AU - Jacobs, Richard F AU - Vaudry, Wendy AU - Pass, Robert F AU - Kiell, Jan M AU - Soong, Seng-jaw AU - Whitley, Richard J AU - National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group AD - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA. dkimberlin@peds.uab.edu ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 16 EP - 25 VL - 143 IS - 1 SN - 0022-3476, 0022-3476 KW - Antiviral Agents KW - 0 KW - Creatinine KW - AYI8EX34EU KW - Ganciclovir KW - P9G3CKZ4P5 KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Calcinosis -- epidemiology KW - Calcinosis -- pathology KW - Double-Blind Method KW - Humans KW - Infant, Newborn KW - Evoked Potentials, Auditory, Brain Stem -- physiology KW - Infant, Premature KW - Splenomegaly -- chemically induced KW - Infant KW - Creatinine -- metabolism KW - Hyperbilirubinemia -- chemically induced KW - Splenomegaly -- epidemiology KW - Brain -- pathology KW - Hepatomegaly -- chemically induced KW - Hyperbilirubinemia -- epidemiology KW - Follow-Up Studies KW - Time Factors KW - Male KW - Female KW - Hepatomegaly -- epidemiology KW - Cytomegalovirus Infections -- drug therapy KW - Antiviral Agents -- therapeutic use KW - Cytomegalovirus Infections -- epidemiology KW - Ganciclovir -- therapeutic use KW - Central Nervous System Viral Diseases -- epidemiology KW - Hearing Loss, Sensorineural -- chemically induced KW - Cytomegalovirus Infections -- congenital KW - Central Nervous System Viral Diseases -- congenital KW - Ganciclovir -- adverse effects KW - Hearing Loss, Sensorineural -- diagnosis KW - Antiviral Agents -- adverse effects KW - Hearing Loss, Sensorineural -- epidemiology KW - Central Nervous System Viral Diseases -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73574094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pediatrics&rft.atitle=Effect+of+ganciclovir+therapy+on+hearing+in+symptomatic+congenital+cytomegalovirus+disease+involving+the+central+nervous+system%3A+a+randomized%2C+controlled+trial.&rft.au=Kimberlin%2C+David+W%3BLin%2C+Chin-Yu%3BS%C3%A1nchez%2C+Pablo+J%3BDemmler%2C+Gail+J%3BDankner%2C+Wayne%3BShelton%2C+Mark%3BJacobs%2C+Richard+F%3BVaudry%2C+Wendy%3BPass%2C+Robert+F%3BKiell%2C+Jan+M%3BSoong%2C+Seng-jaw%3BWhitley%2C+Richard+J%3BNational+Institute+of+Allergy+and+Infectious+Diseases+Collaborative+Antiviral+Study+Group&rft.aulast=Kimberlin&rft.aufirst=David&rft.date=2003-07-01&rft.volume=143&rft.issue=1&rft.spage=16&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pediatrics&rft.issn=00223476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-17 N1 - Date created - 2003-08-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Pediatr. 2003 Jul;143(1):4-6 [12915814] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of latent HIV-1 expression by the potent anti-tumor promoter 12-deoxyphorbol 13-phenylacetate. AN - 73524658; 12895692 AB - Agents that induce HIV-1 out of latency would be useful adjuvants for currently available anti-retroviral therapy. We report that nanomolar concentrations of 12-deoxyphorbol 13-phenylacetate (DPP), an anti-tumor-promoting phorbol ester originally isolated from a West African plant, induce the expression of HIV-1 in latently infected T cells and render them sensitive to killing by an immunotoxin targeted to the viral envelope glycoprotein. DPP also regulates an extensive series of genes under the control of protein kinase C, including several involved in T cell activation and cytoskeleton reorganization, and represses expression of the HIV-1 receptor CD4 and coreceptor CXCR4. DPP is 20-40-fold more potent than the related phorbol ester prostratin, probably due to its more lipophilic side chain structure. The combination of high potency and anti-tumor promoting activity make DPP an attractive candidate for the adjunctive therapy of persistent HIV-1 infection. JF - Antiviral research AU - Bocklandt, Sven AU - Blumberg, Peter M AU - Hamer, Dean H AD - National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 89 EP - 98 VL - 59 IS - 2 SN - 0166-3542, 0166-3542 KW - Anti-HIV Agents KW - 0 KW - Antigens, CD4 KW - Carcinogens KW - Macromolecular Substances KW - Phorbol Esters KW - Receptors, CXCR4 KW - 12-deoxyphorbolphenylacetate KW - 58821-98-0 KW - prostratin KW - 60857-08-1 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Oligonucleotide Array Sequence Analysis KW - Models, Molecular KW - Humans KW - Receptors, CXCR4 -- metabolism KW - Antigens, CD4 -- metabolism KW - Carcinogens -- antagonists & inhibitors KW - Gene Expression Profiling KW - Virus Activation -- drug effects KW - Virus Replication -- drug effects KW - HIV Infections -- drug therapy KW - Protein Kinase C -- chemistry KW - Protein Kinase C -- physiology KW - Down-Regulation -- drug effects KW - Cell Line KW - Anti-HIV Agents -- chemistry KW - Phorbol Esters -- pharmacology KW - Phorbol Esters -- chemistry KW - HIV-1 -- genetics KW - Anti-HIV Agents -- pharmacology KW - HIV-1 -- physiology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73524658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Activation+of+latent+HIV-1+expression+by+the+potent+anti-tumor+promoter+12-deoxyphorbol+13-phenylacetate.&rft.au=Bocklandt%2C+Sven%3BBlumberg%2C+Peter+M%3BHamer%2C+Dean+H&rft.aulast=Bocklandt&rft.aufirst=Sven&rft.date=2003-07-01&rft.volume=59&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 - 2003-11-19 N1 - Date created - 2003-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frontal cortical tissue composition in abstinent cocaine abusers: a magnetic resonance imaging study. AN - 73491916; 12880835 AB - Cocaine abusers exhibit impairment of executive cognitive functions that are mediated by the frontal cortex. This work tested for structural (i.e., tissue composition) abnormalities that may underlie such performance deficits. Research participants were cocaine abusers (n = 14) abstinent for 20 days and a non-drug-using comparison group (n = 11), who underwent magnetic resonance imaging (T1-weighted scans of the brain). Gray matter and white matter tissue densities were determined using voxel-based morphometry with small volume correction based on a priori hypotheses derived from functional imaging of the same subjects. Cocaine abusers had significantly lower gray matter tissue density than did the non drug users in 10 of 13 small volumes analyzed in the frontal cortex [bilateral anterior cingulate gyrus (infragenual and perigenual regions) and medial orbitofrontal cortex and the lateral orbitofrontal cortex and middle/dorsal cingulate gyrus in the right hemisphere]. No group differences were found in white matter density of the frontal cortex. These results extend our previous findings of defective frontal cortical activation (indexed by cerebral blood flow) in cocaine abusers to include abnormalities in gray matter tissue density in the same frontal cortical regions. JF - NeuroImage AU - Matochik, John A AU - London, Edythe D AU - Eldreth, Dana A AU - Cadet, Jean-Lud AU - Bolla, Karen I AD - Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. jmatochi@intra.nida.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 1095 EP - 1102 VL - 19 IS - 3 SN - 1053-8119, 1053-8119 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Gyrus Cinguli -- chemistry KW - Humans KW - Gyrus Cinguli -- metabolism KW - Adult KW - Tomography, Emission-Computed KW - Image Processing, Computer-Assisted KW - Male KW - Functional Laterality -- physiology KW - Female KW - Prefrontal Cortex -- diagnostic imaging KW - Prefrontal Cortex -- metabolism KW - Prefrontal Cortex -- chemistry KW - Cocaine-Related Disorders -- metabolism KW - Cocaine-Related Disorders -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73491916?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NeuroImage&rft.atitle=Frontal+cortical+tissue+composition+in+abstinent+cocaine+abusers%3A+a+magnetic+resonance+imaging+study.&rft.au=Matochik%2C+John+A%3BLondon%2C+Edythe+D%3BEldreth%2C+Dana+A%3BCadet%2C+Jean-Lud%3BBolla%2C+Karen+I&rft.aulast=Matochik&rft.aufirst=John&rft.date=2003-07-01&rft.volume=19&rft.issue=3&rft.spage=1095&rft.isbn=&rft.btitle=&rft.title=NeuroImage&rft.issn=10538119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-09 N1 - Date created - 2003-07-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional regulation of the telomerase hTERT gene as a target for cellular and viral oncogenic mechanisms. AN - 73480177; 12807729 AB - Malignant transformation from mortal, normal cells to immortal, cancer cells is generally associated with activation of telomerase and subsequent telomere maintenance. A major mechanism to regulate telomerase activity in human cells is transcriptional control of the telomerase catalytic subunit gene, human telomerase reverse transcriptase (hTERT). Several transcription factors, including oncogene products (e.g. c-Myc) and tumor suppressor gene products (e.g. WT1 and p53), are able to control hTERT transcription when over-expressed, although it remains to be determined whether a cancer-associated alteration of these factors is primarily responsible for the hTERT activation during carcinogenic processes. Microcell-mediated chromosome transfer experiments have provided evidence for endogenous factors that function to repress the telomerase activity in normal cells and are inactivated in cancer cells. At least one of those endogenous telomerase repressors, which is encoded by a putative tumor suppressor gene on chromosome 3p, acts through transcriptional repression of the hTERT gene. The hTERT gene is also a target site for viruses frequently associated with human cancers, such as human papillomavirus (HPV) and hepatitis B virus (HBV). HPV E6 protein contributes to keratinocyte immortalization and carcinogenesis through trans-activation of the hTERT gene transcription. In at least some hepatocellular carcinomas, the hTERT gene is a non-random integration site of HBV genome, which activates in cis the hTERT transcription. Thus, a variety of cellular and viral oncogenic mechanisms converge on transcriptional control of the hTERT gene. Regulation of chromatin structure through the modification of nucleosomal histones may mediate the action of these cellular and viral mechanisms. Further elucidation of the hTERT transcriptional regulation, including identification and characterization of the endogenous repressor proteins, should lead to better understanding of the complex regulation of human telomerase in normal and cancer cells and may open up new strategies for anticancer therapy. JF - Carcinogenesis AU - Horikawa, Izumi AU - Barrett, J Carl AD - Laboratory of Biosystems and Cancer, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5046, MSC-4264, Bethesda, MD 20892, USA. horikawi@mail.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 1167 EP - 1176 VL - 24 IS - 7 SN - 0143-3334, 0143-3334 KW - DNA-Binding Proteins KW - 0 KW - Telomerase KW - EC 2.7.7.49 KW - Index Medicus KW - Telomere -- metabolism KW - DNA Methylation KW - Papillomaviridae -- physiology KW - Humans KW - Transcription, Genetic KW - Transcriptional Activation KW - Cell Transformation, Viral -- physiology KW - Gene Expression Regulation, Enzymologic -- physiology KW - Telomerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73480177?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transcriptional+regulation+of+the+telomerase+hTERT+gene+as+a+target+for+cellular+and+viral+oncogenic+mechanisms.&rft.au=Horikawa%2C+Izumi%3BBarrett%2C+J+Carl&rft.aulast=Horikawa&rft.aufirst=Izumi&rft.date=2003-07-01&rft.volume=24&rft.issue=7&rft.spage=1167&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-22 N1 - Date created - 2003-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The glucagon-like peptides: a double-edged therapeutic sword? AN - 73479363; 12871671 JF - Trends in pharmacological sciences AU - Perry, TracyAnn AU - Greig, Nigel H AD - Section of Drug Design and Development, Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. perryt@grc.nia.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 377 EP - 383 VL - 24 IS - 7 SN - 0165-6147, 0165-6147 KW - GLP1R protein, human KW - 0 KW - Glucagon-Like Peptide-1 Receptor KW - Insulin KW - Peptide Fragments KW - Peptides KW - Protein Precursors KW - Receptors, Glucagon KW - Venoms KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - exenatide KW - 9P1872D4OL KW - Index Medicus KW - Diabetes Mellitus, Type 2 -- drug therapy KW - Animals KW - Humans KW - Brain -- drug effects KW - Molecular Sequence Data KW - Peptides -- chemistry KW - Insulin -- secretion KW - Diabetes Mellitus, Type 2 -- metabolism KW - Brain -- metabolism KW - Amino Acid Sequence KW - Peptides -- pharmacology KW - Receptors, Glucagon -- biosynthesis KW - Protein Precursors -- pharmacology KW - Receptors, Glucagon -- agonists KW - Glucagon -- chemistry KW - Peptide Fragments -- chemistry KW - Glucagon -- physiology KW - Protein Precursors -- physiology KW - Protein Precursors -- chemistry KW - Peptide Fragments -- pharmacology KW - Glucagon -- pharmacology KW - Peptide Fragments -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73479363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+pharmacological+sciences&rft.atitle=The+glucagon-like+peptides%3A+a+double-edged+therapeutic+sword%3F&rft.au=Perry%2C+TracyAnn%3BGreig%2C+Nigel+H&rft.aulast=Perry&rft.aufirst=TracyAnn&rft.date=2003-07-01&rft.volume=24&rft.issue=7&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Trends+in+pharmacological+sciences&rft.issn=01656147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-11 N1 - Date created - 2003-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of three retrospective exposure assessment methods. AN - 73477517; 12855490 AB - To evaluate three methods for assessing retrospective exposures of acrylonitrile workers. Three methods used to develop historical exposure estimates for a retrospective cohort mortality study of acrylonitrile workers were considered. The first method was deterministic, incorporating estimates of the impact of changes that took place in the workplace. The second method used the ratio of the mean of the measurements for three similar jobs to estimate a fourth similar job. The third method was based on the development of homogeneous exposure groups (HEG). Estimates of acrylonitrile exposure were developed using these three methods and compared with measurement means (observed means) across three categories of airborne exposure concentrations (or=1 p.p.m.) and three categories based on the number of measurements used to develop the estimate (or=30). The correlation between the estimates and the observed values was about 0.65 for all three methods. Estimates using the deterministic method tended to overestimate the observed means by 17%, but the number of estimates was not above or below the observed means more often than expected. There was no statistically significant relationship between the exposure estimates and the acrylonitrile concentration in the air or the number of measurements used to develop the estimates. The estimates averaged within 60% of the observed means when concentrations were above 0.5 p.p.m. and 25% regardless of the number of measurements on which the estimates were based. Estimates from the ratio method were randomly distributed above and below the observed means and averaged 70% above the observed means. The air concentration did not affect the performance of the method, although above 1 p.p.m. the estimates were within 40% of the observed means. The number of measurements comprising the estimates was related on a relative scale to the performance of the method. Exposure estimates using the HEG method were neither greater nor less than the observed means more often than what was expected. The method did better as concentration and the number of measurements increased. The estimates were within 60% of the means at >0.5 p.p.m. and for all measurement categories. Overall, there was no statistically significant difference between the estimates derived from the three estimation methods. All methods performed reasonably well, but the deterministic and HEG methods appeared to develop estimates closer to the observed means for concentrations >0.5 p.p.m., regardless of the number of measurements. JF - The Annals of occupational hygiene AU - Stewart, Patricia A AU - Lees, Peter S J AU - Correa, Adolfo AU - Breysse, Patrick AU - Gail, Mitchell AU - Graubard, Barry I AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Boulevard, MSC 7240, Rockville, MD 20892-7240, USA. stewartt@epndce.nci.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 399 EP - 411 VL - 47 IS - 5 SN - 0003-4878, 0003-4878 KW - Acrylonitrile KW - MP1U0D42PE KW - Index Medicus KW - Reproducibility of Results KW - Humans KW - Cohort Studies KW - Retrospective Studies KW - Occupational Health KW - Data Collection -- methods KW - Acrylonitrile -- analysis KW - Occupational Exposure -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73477517?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+occupational+hygiene&rft.atitle=Evaluation+of+three+retrospective+exposure+assessment+methods.&rft.au=Stewart%2C+Patricia+A%3BLees%2C+Peter+S+J%3BCorrea%2C+Adolfo%3BBreysse%2C+Patrick%3BGail%2C+Mitchell%3BGraubard%2C+Barry+I&rft.aulast=Stewart&rft.aufirst=Patricia&rft.date=2003-07-01&rft.volume=47&rft.issue=5&rft.spage=399&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+occupational+hygiene&rft.issn=00034878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-15 N1 - Date created - 2003-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel direct and indirect cyclin-dependent kinase modulators for the prevention and treatment of human neoplasms. AN - 73474706; 12819936 AB - Abnormalities in the cell cycle are responsible for the majority of human neoplasias. Most abnormalities occur due to hyperphosphorylation of the tumor suppressor gene Rb by the key regulators of the cell cycle, the cyclin-dependent kinases (CDKs). Thus, a pharmacological CDK inhibitor may be useful in the prevention and/or treatment of human neoplasms. Flavopiridol is a flavonoid with interesting preclinical properties: (1) potent CDK inhibitory activity; (2) it depletes cyclin D1 and vascular endothelial growth factor mRNA by transcriptional and posttranscriptional mechanisms, respectively; (3) it inhibits positive elongation factor B, leading to transcription "halt"; and (4) it induces apoptosis in several preclinical models. The first phase I trial of a CDK inhibitor, flavopiridol, has been completed. Dose-limiting toxicities included secretory diarrhea and proinflammatory syndrome. Antitumor activity was observed in some patients with non-Hodgkin's lymphoma and renal, colon, and prostate cancers. Concentrations between 300 and 500 n M-necessary to inhibit CDK-were achieved safely. Phase II trials with infusional flavopiridol and phase I infusional trials in combination with standard chemotherapy are being completed with encouraging results. A novel phase I trial of 1-h flavopiridol administration was recently completed. The maximum tolerated doses using flavopiridol daily for 5, 3, and 1 consecutive days are 37.5, 50, and 62.5 mg/m(2) per day. Dose-limiting toxicities include vomiting, neutropenia, proinflammatory syndrome, and diarrhea. Plasma flavopiridol concentrations achieved were in the range 1.5-3.5 MICRO M. Phase II/III trials using this 1-h schedule in several tumor types including non-small-cell lung cancer, chronic lymphocytic leukemia, mantle cell lymphoma, and head and neck cancer are being conducted worldwide. UCN-01, the second CDK modulator that has entered clinical trials, has unique preclinical properties: (1) it inhibits protein kinase C (PKC) activity; (2) it promotes cell-cycle arrest by accumulation in p21/p27; (3) it induces apoptosis in several preclinical models; and (4) it abrogates the G(2) checkpoint by inhibition of chk1. The last of these represents a novel strategy to combine UCN-01 with DNA-damaging agents. In the initial UCN-01 clinical trial (continuous infusion for 72 h), a prolonged half-life of about 600 h (100 times longer than in preclinical models) was observed. The maximum tolerated dose was 42.5 mg/m(2) per day for 3 days. Dose-limiting toxicities were nausea/vomiting, hypoxemia, and symptomatic hyperglycemia. One patient with melanoma achieved a partial response (8 months). Another patient with refractory anaplastic large-cell lymphoma had no evidence of disease at >4 years. Bone marrow and tumor samples obtained from some patients revealed loss in adducin phosphorylation, a substrate of PKC. Phase I trials with shorter infusions are being completed. In summary, the first two CDK modulators have shown encouraging results in early clinical trials. A question that remains unanswered is "Which is the best schedule for combination with standard antitumor agents?" Moreover, it is still unclear which pharmacodynamic endpoint reflects loss of CDK activity in tissue samples from patients in these trials. Despite these caveats, we feel that CDKs are sensible targets for cancer therapy and that there are several small-molecule CDK modulators in clinical trials with encouraging results. JF - Cancer chemotherapy and pharmacology AU - Senderowicz, Adrian M AD - Molecular Therapeutics Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30, Room 211, Bethesda, MD 20892-4340, USA. adrian.senderowicz@nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - S61 EP - S73 VL - 52 Suppl 1 SN - 0344-5704, 0344-5704 KW - Alkaloids KW - 0 KW - Enzyme Inhibitors KW - Flavonoids KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - 7-hydroxystaurosporine KW - 7BU5H4V94A KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Clinical Trials as Topic KW - Piperidines -- administration & dosage KW - Staurosporine -- analogs & derivatives KW - Cell Cycle -- drug effects KW - Flavonoids -- administration & dosage KW - Alkaloids -- administration & dosage KW - Neoplasms -- drug therapy KW - Neoplasms -- pathology KW - Neoplasms -- enzymology KW - Enzyme Inhibitors -- therapeutic use KW - Enzyme Inhibitors -- pharmacology KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73474706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Novel+direct+and+indirect+cyclin-dependent+kinase+modulators+for+the+prevention+and+treatment+of+human+neoplasms.&rft.au=Senderowicz%2C+Adrian+M&rft.aulast=Senderowicz&rft.aufirst=Adrian&rft.date=2003-07-01&rft.volume=52+Suppl+1&rft.issue=&rft.spage=S61&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-30 N1 - Date created - 2003-07-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Managing occupational risks for hepatitis C transmission in the health care setting. AN - 73469311; 12857782 AB - Hepatitis C virus (HCV) infection is a significant contemporary health problem in the United States and elsewhere. Because it is primarily transmitted via blood, hepatitis C infection presents risks for both nosocomial transmission to patients and occupational spread to health care workers. Recent insights into the pathogenesis, immunopathogenesis, natural history, and treatment of infection caused by this unique flavivirus provide a rationale for the use of new strategies for managing occupational hepatitis C infections when they occur. This article reviews this developing information. Recently published data demonstrate success rates in the treatment of "acute hepatitis C syndrome" that approach 100\%, and although these studies are not directly applicable to all occupational infections, they may provide important clues to optimal management strategies. In addition, the article delineates approaches to the prevention of occupational exposures and also addresses the difficult issue of managing HCV-infected health care providers. The article summarizes currently available data about the nosocomial epidemiology of HCV infection and the magnitude of risk and discusses several alternatives for managing exposure and infection. No evidence supports the use of immediate postexposure prophylaxis with immunoglobulin, immunomodulators, or antiviral agents. Based on the very limited data available, the watchful waiting and preemptive therapy strategies described in detail in this article represent reasonable interim approaches to the complex problem of managing occupational HCV infections, at least until more definitive data are obtained. JF - Clinical microbiology reviews AU - Henderson, David K AD - Warren G. Magnuson Clinical Center, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland 20892, USA. dkh@nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 546 EP - 568 VL - 16 IS - 3 SN - 0893-8512, 0893-8512 KW - Index Medicus KW - Risk KW - Infectious Disease Transmission, Patient-to-Professional KW - Humans KW - Infectious Disease Transmission, Professional-to-Patient KW - Hepatitis C -- prevention & control KW - Hepatitis C -- transmission KW - Occupational Diseases -- prevention & control KW - Hepatitis C -- etiology KW - Occupational Diseases -- etiology KW - Health Personnel UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73469311?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+microbiology+reviews&rft.atitle=Managing+occupational+risks+for+hepatitis+C+transmission+in+the+health+care+setting.&rft.au=Henderson%2C+David+K&rft.aulast=Henderson&rft.aufirst=David&rft.date=2003-07-01&rft.volume=16&rft.issue=3&rft.spage=546&rft.isbn=&rft.btitle=&rft.title=Clinical+microbiology+reviews&rft.issn=08938512&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-22 N1 - Date created - 2003-07-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Gastroenterol Hepatol. 2000 May;15 Suppl:E91-6 [10921389] Semin Liver Dis. 2000;20(2):127-41 [10946419] Bull World Health Organ. 2000;78(8):956-63 [10994278] Infect Control Hosp Epidemiol. 2000 Sep;21(9):619 [11001274] Science. 2000 Sep 22;289(5487):2003 [11032545] Eur J 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Infection. 1997 Mar-Apr;25(2):74-7 [9108179] Hepatology. 1997 May;25(5):1245-9 [9141445] Clin Infect Dis. 1997 May;24(5):992-4 [9142809] Infect Control Hosp Epidemiol. 1997 May;18(5):349-63 [9154481] Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6874-9 [9192659] Am J Infect Control. 1997 Jun;25(3):242-7 [9202821] Clin Exp Immunol. 1997 Oct;110(1):4-8 [9353141] N Engl J Med. 1997 Nov 20;337(21):1485-90 [9366579] Int Immunol. 1997 Nov;9(11):1757-66 [9418136] J Viral Hepat. 1997;4 Suppl 2:31-41 [9429208] Infect Dis Clin North Am. 1998 Mar;12(1):13-26 [9494826] Curr Stud Hematol Blood Transfus. 1998;(62):135-51 [9507808] Clin Infect Dis. 1992 Jun;14(6):1179-85 [1623073] N Engl J Med. 1992 Aug 6;327(6):369-73 [1320736] Blood. 1992 Jul 15;80(2):540-3 [1627805] J Infect Dis. 1992 Oct;166(4):900-3 [1382107] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disseminated vascular papules in an immunodeficient patient being treated with granulocyte colony-stimulating factor. AN - 73467616; 12833018 JF - Journal of the American Academy of Dermatology AU - Lenczowski, Joi M AU - Cassarino, David S AU - Jain, Ashish AU - Turner, Maria L AD - Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1908, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 105 EP - 108 VL - 49 IS - 1 SN - 0190-9622, 0190-9622 KW - Immunoglobulin M KW - 0 KW - Recombinant Proteins KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Index Medicus KW - Neutropenia -- etiology KW - Humans KW - Adult KW - Chromosomes, Human, X KW - Neutropenia -- drug therapy KW - Male KW - Granuloma, Pyogenic -- immunology KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Granuloma, Pyogenic -- chemically induced KW - Granulocyte Colony-Stimulating Factor -- adverse effects KW - Immunologic Deficiency Syndromes -- drug therapy KW - Skin Diseases -- pathology KW - Granuloma, Pyogenic -- pathology KW - Skin Diseases -- chemically induced KW - Immunologic Deficiency Syndromes -- complications KW - Hypergammaglobulinemia -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73467616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=proceeding&rft.jtitle=Journal+of+the+American+Academy+of+Dermatology&rft.atitle=Disseminated+vascular+papules+in+an+immunodeficient+patient+being+treated+with+granulocyte+colony-stimulating+factor.&rft.au=Lenczowski%2C+Joi+M%3BCassarino%2C+David+S%3BJain%2C+Ashish%3BTurner%2C+Maria+L&rft.aulast=Lenczowski&rft.aufirst=Joi&rft.date=2003-07-01&rft.volume=49&rft.issue=1&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Dermatology&rft.issn=01909622&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-31 N1 - Date created - 2003-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2-[18F]F-A-85380: PET imaging of brain nicotinic acetylcholine receptors and whole body distribution in humans. AN - 73466222; 12759330 AB - Noninvasive imaging of nicotinic acetylcholine receptors (nAChRs) in the human brain in vivo is critical for elucidating the role of these receptors in normal brain function and in the pathogenesis of brain disorders. Here we report the first in vivo visualization of human brain areas containing nAChRs by using PET and 2-[18F]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2-[18F]FA). We acquired scans from six healthy non-smoking volunteers after i.v. bolus administration of 2-[18F]FA (1.6 MBq/kg or 0.043 +/- 0.002 mCi/kg). This dose was sufficient for visualizing nAChRs in the thalamus up to 5 h after injection. There were no adverse effects associated with administration of no-carrier-added 2-[18F]FA (1.3-10 pmol/kg). Consistent with the distribution of nAChRs in human brain, accumulated radioactivity was greatest in thalamus, intermediate in the midbrain, pons, cerebellum, and cortex; and least in white matter. As approximately 90% of the injected radioactivity was eliminated via the urine (biological half-life ca. 4 h), the urinary bladder wall received the highest radiation dose. The estimate of radiation dose equivalent to the urinary bladder wall (ca. 180 +/- 30 mSv/MBq or 0.7 rem/mCi with a 2.4 h void interval) suggests that multiple studies could be performed in a single subject. The results predict that quantitative PET imaging of nAChRs in human brain with 2-[18F]FA is feasible. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Kimes, Alane S AU - Horti, Andrew G AU - London, Edythe D AU - Chefer, Svetlana I AU - Contoreggi, Carlo AU - Ernst, Monique AU - Friello, Phyllis AU - Koren, Andrei O AU - Kurian, Varughese AU - Matochik, John A AU - Pavlova, Olga AU - Vaupel, D Bruce AU - Mukhin, Alexey G AD - NIDA Intramural Research Program; Baltimore, Maryland 21224, USA. akimes@intra.nida.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 1331 EP - 1333 VL - 17 IS - 10 KW - 2-fluoro-3-(2-azetidinylmethoxy)pyridine KW - 0 KW - Azetidines KW - Ligands KW - Pyridines KW - Receptors, Nicotinic KW - Index Medicus KW - Radiation Dosage KW - Humans KW - Brain Chemistry KW - Tissue Distribution KW - Female KW - Pyridines -- pharmacokinetics KW - Receptors, Nicotinic -- analysis KW - Tomography, Emission-Computed KW - Pyridines -- adverse effects KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73466222?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=2-%5B18F%5DF-A-85380%3A+PET+imaging+of+brain+nicotinic+acetylcholine+receptors+and+whole+body+distribution+in+humans.&rft.au=Kimes%2C+Alane+S%3BHorti%2C+Andrew+G%3BLondon%2C+Edythe+D%3BChefer%2C+Svetlana+I%3BContoreggi%2C+Carlo%3BErnst%2C+Monique%3BFriello%2C+Phyllis%3BKoren%2C+Andrei+O%3BKurian%2C+Varughese%3BMatochik%2C+John+A%3BPavlova%2C+Olga%3BVaupel%2C+D+Bruce%3BMukhin%2C+Alexey+G&rft.aulast=Kimes&rft.aufirst=Alane&rft.date=2003-07-01&rft.volume=17&rft.issue=10&rft.spage=1331&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-17 N1 - Date created - 2003-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer risks from medical radiation. AN - 73461462; 12852471 AB - About 15% of the ionizing radiation exposure to the general public comes from artificial sources, and almost all of this exposure is due to medical radiation, largely from diagnostic procedures. Of the approximately 3 mSv annual global per caput effective dose estimated for the year 2000, 2.4 mSv is from natural background and 0.4 mSv from diagnostic medical exams. Diagnostic and therapeutic radiation was used in patients as early as 1896. Since then, continual improvements in diagnostic imaging and radiotherapy as well as the aging of our population have led to greater use of medical radiation. Temporal trends indicate that worldwide population exposure from medical radiation is increasing. In the United States, there has been a steady rise in the use of diagnostic radiologic procedures, especially x rays. Radiotherapy also has increased so that today about 40% of cancer patients receive some treatment with radiation. Epidemiologic data on medically irradiated populations are an important complement to the atomic-bomb survivors' studies. Significant improvement in cancer treatment over the last few decades has resulted in longer survival and a growing number of radiation-related second cancers. Following high-dose radiotherapy for malignant diseases, elevated risks of a variety of radiation-related second cancers have been observed. Risks have been particularly high following treatment for childhood cancer. Radiation treatment for benign disease was relatively common from the 1940's to the 1960's. While these treatments generally were effective, some resulted in enhanced cancer risks. As more was learned about radiation-associated cancer risks and new treatments became available, the use of radiotherapy for benign disease has declined. At moderate doses, such as those used to treat benign diseases, radiation-related cancers occur in or near the radiation field. Cancers of the thyroid, salivary gland, central nervous system, skin, and breast as well as leukemia have been associated with radiotherapy for tinea capitis, enlarged tonsils or thymus gland, other benign conditions of the head and neck, or benign breast diseases. Because doses from diagnostic examinations typically are low, they are difficult to study using epidemiologic methods, unless multiple examinations are performed. An excess risk of breast cancer has been reported among women with tuberculosis who had multiple chest fluoroscopies as well as among scoliosis patients who had frequent diagnostic x rays during late childhood and adolescence. Dental and medical diagnostic x rays performed many years ago, when doses were presumed to be high, also have been linked to increased cancer risks. The carcinogenic effects of diagnostic and therapeutic radionuclides are less well characterized. High risks of liver cancer and leukemia have been demonstrated following thorotrast injections, and patients treated with radium appear to have an elevated risk of bone sarcomas and possibly cancers of the breast, liver, kidney, thyroid, and bladder. JF - Health physics AU - Ron, Elaine AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, EPS 7048, 6120 Executive Boulevard, Bethesda, MD 20892, USA. eron@mail.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 47 EP - 59 VL - 85 IS - 1 SN - 0017-9078, 0017-9078 KW - Radiopharmaceuticals KW - 0 KW - Index Medicus KW - Radiopharmaceuticals -- therapeutic use KW - Radiation Dosage KW - Risk Factors KW - Radiotherapy Dosage KW - Humans KW - Radiometry -- methods KW - Radiography -- utilization KW - Neoplasms, Radiation-Induced -- epidemiology KW - Neoplasms, Radiation-Induced -- mortality KW - Risk Assessment -- methods KW - Radionuclide Imaging -- utilization KW - Radiotherapy -- utilization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73461462?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+physics&rft.atitle=Cancer+risks+from+medical+radiation.&rft.au=Ron%2C+Elaine&rft.aulast=Ron&rft.aufirst=Elaine&rft.date=2003-07-01&rft.volume=85&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Health+physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-25 N1 - Date created - 2003-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prion protein trafficking and the development of neurodegeneration. AN - 73456752; 12850426 AB - The prion protein (PrP) is involved in causing a group of diverse transmissible, heritable and sporadically occurring neurodegenerative diseases. Although the identity, nature and replication of the transmissible agent have been intensely studied for decades, the cellular events underlying neuronal dysfunction and death have received comparatively little attention. Recent studies examining the occurrence and consequences of inappropriate cytoplasmic expression of the normally cell-surface PrP underscore an emerging role for PrP trafficking in prion disease pathogenesis. JF - Trends in neurosciences AU - Hegde, Ramanujan S AU - Rane, Neena S AD - Cell Biology and Metabolism Branch, NICHD/National Institutes of Health, Bethesda, MD 20892, USA. hegder@mail.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 337 EP - 339 VL - 26 IS - 7 SN - 0166-2236, 0166-2236 KW - Prions KW - 0 KW - Index Medicus KW - Animals KW - Signal Transduction KW - Prions -- toxicity KW - Nerve Degeneration -- metabolism KW - Cytoplasm -- metabolism KW - Prions -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73456752?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+neurosciences&rft.atitle=Prion+protein+trafficking+and+the+development+of+neurodegeneration.&rft.au=Hegde%2C+Ramanujan+S%3BRane%2C+Neena+S&rft.aulast=Hegde&rft.aufirst=Ramanujan&rft.date=2003-07-01&rft.volume=26&rft.issue=7&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Trends+in+neurosciences&rft.issn=01662236&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-29 N1 - Date created - 2003-07-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Science. 2002 Nov 29;298(5599):1785-8 [12386336] Science. 2002 Nov 29;298(5599):1781-5 [12386337] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogenic endocrine disruptive components interfere with calcium handling and differentiation of human trophoblast cells. AN - 73456460; 12858341 AB - During development, calcium (Ca) is actively transported by placental trophoblasts to meet fetal nutritional and the skeletal mineralization needs. Maternal exposure to estrogenic pesticides, such as 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT) and methoxychlor (MTC), has been shown to result in reproductive disorders and/or abnormal fetal development. In this study, we have examined the effects of exposure of trophoblastic cells to MTC and DTT, in comparison to 17beta-estradiol (E2) and diethylstilbestrol (DES), to test the hypothesis that cellular Ca handling is a target for these endocrine disruptive components. Treatment with DDT, MTC, DES, or E2 increased cellular Ca uptake, and the expression of trophoblast-specific human Ca binding protein (HCaBP) was down-regulated by both MTC and DDT. Treatment with MTC, DDT, and DES inhibited cell proliferation, induced apoptosis, and suppressed expression of several trophoblast differentiation marker genes. These effects were reversed by overexpression of metallothionein IIa, a gene highly responsive to cadmium and other metals. These results strongly suggest that trophoblast Ca handling functions are endocrinally modulated, and that their alteration by candidate endocrine disruptors, such as MTC and DDT, constitutes a possible pathway of the harmful effects of these components on fetal development. Copyright 2003 Wiley-Liss, Inc. JF - Journal of cellular biochemistry AU - Derfoul, A AU - Lin, F J AU - Awumey, E M AU - Kolodzeski, T AU - Hall, D J AU - Tuan, R S AD - Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/07/01/ PY - 2003 DA - 2003 Jul 01 SP - 755 EP - 770 VL - 89 IS - 4 SN - 0730-2312, 0730-2312 KW - Calcium-Binding Proteins KW - 0 KW - Genetic Markers KW - Receptors, Estrogen KW - Receptors, Progesterone KW - Estradiol KW - 4TI98Z838E KW - Diethylstilbestrol KW - 731DCA35BT KW - Metallothionein KW - 9038-94-2 KW - DDT KW - CIW5S16655 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Methoxychlor KW - RIA79UD69L KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Receptors, Progesterone -- biosynthesis KW - Receptors, Estrogen -- biosynthesis KW - Humans KW - Adenosine Triphosphatases -- metabolism KW - Cell Division -- drug effects KW - Receptors, Estrogen -- analysis KW - Calcium-Binding Proteins -- biosynthesis KW - Receptors, Progesterone -- analysis KW - Down-Regulation KW - Enzyme Activation -- drug effects KW - Cell Differentiation -- drug effects KW - Metallothionein -- pharmacology KW - Calcium-Binding Proteins -- drug effects KW - Cell Line KW - Metallothionein -- metabolism KW - Estradiol -- analogs & derivatives KW - Estradiol -- adverse effects KW - Calcium -- metabolism KW - Diethylstilbestrol -- adverse effects KW - Trophoblasts -- cytology KW - Methoxychlor -- adverse effects KW - Trophoblasts -- drug effects KW - Trophoblasts -- metabolism KW - DDT -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73456460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry&rft.atitle=Estrogenic+endocrine+disruptive+components+interfere+with+calcium+handling+and+differentiation+of+human+trophoblast+cells.&rft.au=Derfoul%2C+A%3BLin%2C+F+J%3BAwumey%2C+E+M%3BKolodzeski%2C+T%3BHall%2C+D+J%3BTuan%2C+R+S&rft.aulast=Derfoul&rft.aufirst=A&rft.date=2003-07-01&rft.volume=89&rft.issue=4&rft.spage=755&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry&rft.issn=07302312&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-17 N1 - Date created - 2003-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Baroreflex failure as a late sequela of neck irradiation. AN - 73450584; 12782644 AB - Combined chemotherapy and radiotherapy increase long-term survival in patients with head and neck tumors. Late complications of treatment, however, are being recognized increasingly. Surgery or radiotherapy of the carotid sinuses or brain stem can evoke labile hypertension and orthostatic intolerance from acute or subacute baroreflex failure. Here we report cases in which chronic baroreflex failure appeared to develop as a late sequela of neck irradiation. Three patients referred for autonomic nervous system function testing had labile blood pressure and chronic orthostatic intolerance that developed years after neck irradiation for cancer. In each patient, heart rate remained constant during performance of the Valsalva maneuver, suggesting baroreflex-cardiovagal failure. All 3 patients had virtually zero baroreflex-cardiovagal gain, quantified by interbeat interval-systolic blood pressure relationships after intravenous phenylephrine or nitroglycerine. Ambulatory blood pressure monitoring revealed highly variable blood pressure, with sudden pressor and depressor episodes, a characteristic feature of baroreflex failure. Cardiovagal efferent function, assessed by power spectral analysis of heart rate variability during slow, deep respiration, was normal. Sympathetic noradrenergic efferent function, assessed by cold pressor testing and plasma catecholamine levels during supine rest and orthostasis, was also normal or increased. These findings indicated a primarily afferent lesion. Carotid ultrasonography revealed intimal thickening and atheromatous plaques in all 3 patients. We propose that labile hypertension and orthostatic intolerance can develop as a late sequela of neck irradiation, due to chronic carotid baroreflex failure, which in turn is due to radiation-induced accelerated development of carotid arteriosclerosis. Splinting of carotid sinus mechanoreceptors in rigidified arterial walls would impede detection of alterations in blood pressure and thereby disrupt baroreflex regulation of cardiovagal and sympathetic outflows. JF - Hypertension (Dallas, Tex. : 1979) AU - Sharabi, Yehonatan AU - Dendi, Raghuveer AU - Holmes, Courtney AU - Goldstein, David S AD - Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md 20892-1620, USA. sharabiy@ninds.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 110 EP - 116 VL - 42 IS - 1 KW - Catecholamines KW - 0 KW - Index Medicus KW - Heart Rate KW - Catecholamines -- blood KW - Carotid Artery Diseases -- etiology KW - Blood Pressure KW - Blood Pressure Monitoring, Ambulatory KW - Humans KW - Valsalva Maneuver KW - Middle Aged KW - Autonomic Nervous System -- physiopathology KW - Ultrasonography KW - Male KW - Female KW - Carotid Artery Diseases -- diagnostic imaging KW - Carotid Arteries -- physiopathology KW - Baroreflex KW - Hypertension -- physiopathology KW - Hypertension -- etiology KW - Head and Neck Neoplasms -- radiotherapy KW - Radiotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73450584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.atitle=Baroreflex+failure+as+a+late+sequela+of+neck+irradiation.&rft.au=Sharabi%2C+Yehonatan%3BDendi%2C+Raghuveer%3BHolmes%2C+Courtney%3BGoldstein%2C+David+S&rft.aulast=Sharabi&rft.aufirst=Yehonatan&rft.date=2003-07-01&rft.volume=42&rft.issue=1&rft.spage=110&rft.isbn=&rft.btitle=&rft.title=Hypertension+%28Dallas%2C+Tex.+%3A+1979%29&rft.issn=1524-4563&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-11 N1 - Date created - 2003-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The genotoxicity of tamoxifen: extent and consequences, Kona, Hawaii, January 23, 2003. AN - 73442624; 12840114 AB - The current recommended adjuvant therapy for oestrogen receptor-positive breast cancer typically includes 20 mg/day tamoxifen (Nolvadex) for 5 years post-operatively. This regimen has been found to reduce the incidence of contralateral breast cancer in breast cancer survivors by 47%, and, when used prophylactically, to reduce new breast cancers in high risk women by 49%. However, epidemiological evidence links tamoxifen therapy to increases in endometrial cancer and thromboembolic events in breast cancer patients. In addition, in tamoxifen-exposed rats dose-related increases in hepatic tamoxifen-DNA adduct formation and liver tumour incidence occur through a classic genotoxic mechanism. In women, endometrial cancers may be the result of genotoxicity, hormonally induced signal transduction and/or other mechanisms. If genotoxicity is relevant to tamoxifen-induced endometrial cancer it may be possible to identify women at risk through detection of tamoxifen-DNA adducts. The aim of this one day conference was to examine the most recent evidence for the occurrence of tamoxifen-induced genotoxicity in women receiving tamoxifen therapy. There were significant experimental differences, as some participants presented evidence for a genotoxic mechanism, while others reported finding insufficient evidence to support a genotoxic mechanism. The discussion was wide ranging and the outcome underscored the need for further investigations, access to more human tissue samples, shared tamoxifen-DNA standards for methodological comparisons and inter-laboratory exchange of human tissue samples. JF - Mutagenesis AU - Poirier, Miriam C AU - Schild, Laura J AD - Center for Cancer Research, National Cancer Institute, 37 Convent Drive MSC-4255, National Institutes of Health, Bethesda, MD 20892-4255, USA. poirierm@exchange.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 395 EP - 399 VL - 18 IS - 4 SN - 0267-8357, 0267-8357 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Mutagens KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - Rats KW - Animals KW - Liver -- drug effects KW - Endometrium -- drug effects KW - Humans KW - Hawaii KW - Congresses as Topic KW - Female KW - Tamoxifen -- toxicity KW - Mutagens -- toxicity KW - Antineoplastic Agents, Hormonal -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73442624?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutagenesis&rft.atitle=The+genotoxicity+of+tamoxifen%3A+extent+and+consequences%2C+Kona%2C+Hawaii%2C+January+23%2C+2003.&rft.au=Poirier%2C+Miriam+C%3BSchild%2C+Laura+J&rft.aulast=Poirier&rft.aufirst=Miriam&rft.date=2003-07-01&rft.volume=18&rft.issue=4&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-10 N1 - Date created - 2003-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acamprosate for the adjunctive treatment of alcohol dependence. AN - 73441566; 12841823 AB - To review the literature related to the treatment of alcohol dependence with acamprosate, a synthetic compound structurally similar to the naturally occurring amino acid, homotaurine. Primary literature and review articles were identified by MEDLINE search (1966-June 2003). Abstracts from recent meetings were also reviewed. Acamprosate has been marketed in 24 countries. Although the precise mechanism of acamprosate in the treatment of alcohol-dependent patients is unclear, it may restore the balance between inhibitory and excitatory neurotransmission in the central nervous system. European trials have shown consistent increases in abstinence rates compared with placebo when acamprosate use was paired with appropriate psychosocial and behavioral therapies. Decreased direct and indirect healthcare costs associated with acamprosate treatment have also been reported. Acamprosate is a promising medication for the treatment of alcohol dependence in the US. JF - The Annals of pharmacotherapy AU - Overman, Gerald P AU - Teter, Christian J AU - Guthrie, Sally K AD - Clinical Center Pharmacy Department, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-1196, USA. goverman@cc.nih.gov PY - 2003 SP - 1090 EP - 1099 VL - 37 IS - 7-8 SN - 1060-0280, 1060-0280 KW - Alcohol Deterrents KW - 0 KW - Taurine KW - 1EQV5MLY3D KW - acamprosate KW - N4K14YGM3J KW - Index Medicus KW - Kidney Diseases -- metabolism KW - Drug Interactions KW - Liver Diseases -- complications KW - Biopharmaceutics KW - Kidney Diseases -- complications KW - Humans KW - Drug Approval KW - Clinical Trials as Topic KW - Male KW - Female KW - Liver Diseases -- metabolism KW - Alcohol Deterrents -- adverse effects KW - Taurine -- adverse effects KW - Taurine -- therapeutic use KW - Taurine -- pharmacology KW - Alcohol Deterrents -- pharmacology KW - Alcoholism -- drug therapy KW - Taurine -- economics KW - Taurine -- analogs & derivatives KW - Alcohol Deterrents -- pharmacokinetics KW - Taurine -- pharmacokinetics KW - Alcohol Deterrents -- administration & dosage KW - Alcohol Deterrents -- economics KW - Taurine -- administration & dosage KW - Alcohol Deterrents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73441566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+pharmacotherapy&rft.atitle=Acamprosate+for+the+adjunctive+treatment+of+alcohol+dependence.&rft.au=Overman%2C+Gerald+P%3BTeter%2C+Christian+J%3BGuthrie%2C+Sally+K&rft.aulast=Overman&rft.aufirst=Gerald&rft.date=2003-07-01&rft.volume=37&rft.issue=7-8&rft.spage=1090&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+pharmacotherapy&rft.issn=10600280&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-03 N1 - Date created - 2003-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peroxisome proliferator-activated receptor-alpha agonist treatment in a transgenic model of type 2 diabetes reverses the lipotoxic state and improves glucose homeostasis. AN - 73438816; 12829645 AB - Abnormalities in insulin action are the characteristics of type 2 diabetes. Dominant-negative muscle-specific IGF-I receptor (MKR) mice exhibit elevated lipid levels at an early age and eventually develop type 2 diabetes. To evaluate the role of elevated lipids in the progression of the diabetic state, MKR mice were treated with WY14,643, a peroxisome proliferator-activated receptor (PPAR)-alpha agonist. WY14,643 treatment markedly reduced serum fatty acid and triglyceride levels within a few days, as well as muscle triglyceride levels, and subsequently normalized glucose and insulin levels in MKR mice. Hyperinsulinemic-euglycemic clamp analysis showed that WY14,643 treatment enhanced muscle and adipose tissue glucose uptake by improving whole-body insulin sensitivity. Insulin suppression of endogenous glucose production by the liver of MKR mice was also improved. The expression of genes involved in fatty acid oxidation was increased in liver and skeletal muscle, whereas gene expression levels of hepatic gluconeogenic enzymes were decreased in WY14,643-treated MKR mice. WY14,643 treatment also improved the pattern of glucose-stimulated insulin secretion from the perfused pancreata of MKR mice and reduced the beta-cell mass. Taken together, these findings suggest that the reduction in circulating or intracellular lipids by activation of PPAR-alpha improved insulin sensitivity and the diabetic condition of MKR mice. JF - Diabetes AU - Kim, Hyunsook AU - Haluzik, Martin AU - Asghar, Zeenat AU - Yau, Daphne AU - Joseph, Jamie W AU - Fernandez, Ana M AU - Reitman, Marc L AU - Yakar, Shoshana AU - Stannard, Bethel AU - Heron-Milhavet, Lisa AU - Wheeler, Michael B AU - LeRoith, Derek AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1758, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 1770 EP - 1778 VL - 52 IS - 7 SN - 0012-1797, 0012-1797 KW - Lipids KW - 0 KW - Pyrimidines KW - RNA, Messenger KW - RNA, Ribosomal, 18S KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Triglycerides KW - pirinixic acid KW - 86C4MRT55A KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Glucose KW - IY9XDZ35W2 KW - Abridged Index Medicus KW - Index Medicus KW - Lipids -- blood KW - Animals KW - Pyrimidines -- pharmacology KW - Liver -- metabolism KW - Mice KW - Homeostasis KW - RNA, Messenger -- genetics KW - Mice, Transgenic KW - Muscle, Skeletal -- drug effects KW - RNA, Ribosomal, 18S -- drug effects KW - Gluconeogenesis -- drug effects KW - Mice, Inbred Strains KW - Liver -- drug effects KW - Kinetics KW - Glucose Clamp Technique KW - RNA, Ribosomal, 18S -- genetics KW - Time Factors KW - Muscle, Skeletal -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- agonists KW - Receptor, IGF Type 1 -- physiology KW - Transcription Factors -- drug effects KW - Transcription Factors -- agonists KW - Glucose -- metabolism KW - Triglycerides -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- drug effects KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Receptor, IGF Type 1 -- genetics KW - Diabetes Mellitus, Type 2 -- blood KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73438816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes&rft.atitle=Peroxisome+proliferator-activated+receptor-alpha+agonist+treatment+in+a+transgenic+model+of+type+2+diabetes+reverses+the+lipotoxic+state+and+improves+glucose+homeostasis.&rft.au=Kim%2C+Hyunsook%3BHaluzik%2C+Martin%3BAsghar%2C+Zeenat%3BYau%2C+Daphne%3BJoseph%2C+Jamie+W%3BFernandez%2C+Ana+M%3BReitman%2C+Marc+L%3BYakar%2C+Shoshana%3BStannard%2C+Bethel%3BHeron-Milhavet%2C+Lisa%3BWheeler%2C+Michael+B%3BLeRoith%2C+Derek&rft.aulast=Kim&rft.aufirst=Hyunsook&rft.date=2003-07-01&rft.volume=52&rft.issue=7&rft.spage=1770&rft.isbn=&rft.btitle=&rft.title=Diabetes&rft.issn=00121797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-19 N1 - Date created - 2003-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prion proteins meet protein quality control. AN - 73437598; 12837603 AB - Recent work on transmissible spongiform encephalopathies (TSEs) suggests a role for protein quality-control mechanisms in both prion protein aggregation and pathogenesis. Cytosolic accumulation of prion protein seems to be neurotoxic and might occur when proteasome function is compromised and quality control is overwhelmed. These findings are discussed in the light of other studies linking proteasome inhibition and neurodegeneration. JF - Trends in cell biology AU - Dimcheff, Derek E AU - Portis, John L AU - Caughey, Byron AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases/NIH, Hamilton, MT 59840, USA. ddimcheff@nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 337 EP - 340 VL - 13 IS - 7 SN - 0962-8924, 0962-8924 KW - Multienzyme Complexes KW - 0 KW - PrPC Proteins KW - PrPSc Proteins KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Multienzyme Complexes -- metabolism KW - Cytosol -- metabolism KW - Animals KW - Nerve Degeneration -- metabolism KW - Nerve Degeneration -- physiopathology KW - Humans KW - Cysteine Endopeptidases -- metabolism KW - Protein Transport -- physiology KW - Prion Diseases -- metabolism KW - Neurons -- metabolism KW - Prion Diseases -- physiopathology KW - PrPC Proteins -- metabolism KW - Protein Folding KW - PrPSc Proteins -- metabolism KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73437598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+cell+biology&rft.atitle=Prion+proteins+meet+protein+quality+control.&rft.au=Dimcheff%2C+Derek+E%3BPortis%2C+John+L%3BCaughey%2C+Byron&rft.aulast=Dimcheff&rft.aufirst=Derek&rft.date=2003-07-01&rft.volume=13&rft.issue=7&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=Trends+in+cell+biology&rft.issn=09628924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-05 N1 - Date created - 2003-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - EEG phenotype in alcoholism: increased coherence in the depressive subtype. AN - 73435867; 12807377 AB - Electroencephalography (EEG) power and coherence changes may be trait markers for alcoholism providing clues to brain mechanisms of vulnerability. However, it is unclear whether alpha power and coherence differences reflect reversible toxic or withdrawal effects of alcohol. The EEGs of 10 non-abstinent and 16 long-term abstinent alcoholics (7.7 +/- 5.8 years) and 25 controls were analyzed. Levels of anxiety and depression were assessed by questionnaire. No statistically significant EEG power differences were observed between groups, although the numerical difference between alcoholics and controls was similar to that previously reported. Bilateral, intrahemispheric, posterior coherences were significantly increased in the alpha and beta frequency bands both in long-term abstinent and non-abstinent alcohol-dependent subjects - particularly when depressiveness was included as a covariate. These results suggest that increased EEG-coherence (cortical synchronization) may serve as endophenotype for alcoholism in conjunction with increased depressiveness and point to a possible involvement of GABAergic and/or glutamatergic neurotransmission. JF - Acta psychiatrica Scandinavica AU - Winterer, G AU - Enoch, M-A AU - White, K V AU - Saylan, M AU - Coppola, R AU - Goldman, D AD - Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. wintereg@intra.nimh.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 51 EP - 60 VL - 108 IS - 1 SN - 0001-690X, 0001-690X KW - Index Medicus KW - Brain Mapping KW - Analysis of Variance KW - Humans KW - Adult KW - Temperance -- psychology KW - Time Factors KW - Temperance -- statistics & numerical data KW - Male KW - Female KW - Phenotype KW - Brain -- physiopathology KW - Electroencephalography -- psychology KW - Depressive Disorder -- psychology KW - Depressive Disorder -- physiopathology KW - Alcoholism -- physiopathology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73435867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+psychiatrica+Scandinavica&rft.atitle=EEG+phenotype+in+alcoholism%3A+increased+coherence+in+the+depressive+subtype.&rft.au=Winterer%2C+G%3BEnoch%2C+M-A%3BWhite%2C+K+V%3BSaylan%2C+M%3BCoppola%2C+R%3BGoldman%2C+D&rft.aulast=Winterer&rft.aufirst=G&rft.date=2003-07-01&rft.volume=108&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Acta+psychiatrica+Scandinavica&rft.issn=0001690X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-21 N1 - Date created - 2003-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preoperative FLAC/granulocyte-colony-stimulating factor chemotherapy for stage II breast cancer: a prospective randomized trial. AN - 73432998; 12839848 AB - Preoperative chemotherapy for stage II breast cancer may reduce locoregional tumors and provides initial treatment for systemic micrometastases. We conducted a prospective, randomized trial to evaluate the ability of intensive preoperative chemotherapy to enhance the outcome of this approach. Patients with clinical stage II breast cancer (T2N0, T1N1, and T2N1) were prospectively randomized to receive either preoperative or postoperative chemotherapy with five 21-day cycles of fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamide (FLAC)/granulocyte-colony-stimulating factor. Local therapy consisted of modified radical mastectomy or segmentectomy/axillary dissection/breast radiotherapy, according to patient preference. Fifty-three women were randomized (26 preoperative chemotherapy and 27 postoperative chemotherapy). The objective clinical response rate of the primary tumor to preoperative chemotherapy was 80%, and the pathologic complete response rate was 20%. Preoperative chemotherapy reduced the overall incidence and number of axillary lymph node metastases. There was no difference in the use of breast-conserving local therapy between the two treatment arms. There were 20 local/regional or distant recurrences (9 preoperative and 11 postoperative). There was no difference in the overall or disease-free survival between the preoperative and postoperative chemotherapy arms. Preoperative FLAC/granulocyte-colony-stimulating factor chemotherapy was effective against local/regional tumors in stage II breast cancer but was otherwise comparable to postoperative chemotherapy. JF - Annals of surgical oncology AU - Danforth, David N AU - Cowan, Kenneth AU - Altemus, Rosemary AU - Merino, Maria AU - Chow, Catherine AU - Berman, Arlene AU - Chaudhry, Usha AU - Shriver, Craig AU - Steinberg, Seth M AU - Zujewski, JoAnne AD - Surgery Branch, Center for Cancer Research of the National Cancer Institute, Bethesda, Maryland, USA. david_danforth@nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 635 EP - 644 VL - 10 IS - 6 SN - 1068-9265, 1068-9265 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Doxorubicin KW - 80168379AG KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Cyclophosphamide KW - 8N3DW7272P KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Disease-Free Survival KW - Injections, Intravenous KW - Infusions, Intravenous KW - Combined Modality Therapy KW - Leucovorin -- administration & dosage KW - Humans KW - Prognosis KW - Aged KW - Doxorubicin -- administration & dosage KW - Fluorouracil -- administration & dosage KW - Granulocyte-Macrophage Colony-Stimulating Factor -- administration & dosage KW - Radiotherapy, Adjuvant KW - Adult KW - Treatment Outcome KW - Injections, Subcutaneous KW - Middle Aged KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Female KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology KW - Mastectomy, Segmental KW - Neoadjuvant Therapy KW - Mastectomy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Breast Neoplasms -- surgery KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73432998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+surgical+oncology&rft.atitle=Preoperative+FLAC%2Fgranulocyte-colony-stimulating+factor+chemotherapy+for+stage+II+breast+cancer%3A+a+prospective+randomized+trial.&rft.au=Danforth%2C+David+N%3BCowan%2C+Kenneth%3BAltemus%2C+Rosemary%3BMerino%2C+Maria%3BChow%2C+Catherine%3BBerman%2C+Arlene%3BChaudhry%2C+Usha%3BShriver%2C+Craig%3BSteinberg%2C+Seth+M%3BZujewski%2C+JoAnne&rft.aulast=Danforth&rft.aufirst=David&rft.date=2003-07-01&rft.volume=10&rft.issue=6&rft.spage=635&rft.isbn=&rft.btitle=&rft.title=Annals+of+surgical+oncology&rft.issn=10689265&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-17 N1 - Date created - 2003-07-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Surg Oncol. 2003 Aug;10(7):716-7 [12900360] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smad3 regulates senescence and malignant conversion in a mouse multistage skin carcinogenesis model. AN - 73432770; 12839923 AB - Transforming growth factor beta (TGF-beta) is a growth-inhibitory cytokine for epithelial cells. In the mouse multistage skin carcinogenesis model, defects in TGF-beta 1 signaling reduce senescence in vitro and accelerate malignant progression in vivo. However, the precise postreceptor signaling pathways and specific roles played by Smad proteins in this process have not been defined. Here we show that senescence of v-ras(Ha)-transduced Smad3 null keratinocytes is delayed, whereas overexpression of Smad3, but not Smad2 or Smad4, induced senescence. The TGF-beta 1 target genes c-myc and p15(ink4b) were deregulated in the absence of Smad3. When transplanted to a graft site on nude mice, the v-ras(Ha)-transduced Smad3 null keratinocytes underwent rapid conversion from benign papilloma to malignant carcinoma, whereas wild-type keratinocytes predominantly formed papillomas. These results link Smad3-mediated regulation of growth control genes to senescence in vitro and tumor suppression in vivo. JF - Cancer research AU - Vijayachandra, Kinnimulki AU - Lee, Jessica AU - Glick, Adam B AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/07/01/ PY - 2003 DA - 2003 Jul 01 SP - 3447 EP - 3452 VL - 63 IS - 13 SN - 0008-5472, 0008-5472 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Mice KW - Mice, Nude KW - Keratinocytes -- physiology KW - Base Sequence KW - Promoter Regions, Genetic KW - Cells, Cultured KW - Signal Transduction -- genetics KW - Keratinocytes -- pathology KW - Transforming Growth Factor beta -- genetics KW - Cell Transformation, Neoplastic -- genetics KW - Skin Neoplasms -- genetics KW - Papilloma -- pathology KW - Carcinoma -- pathology KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- genetics KW - Skin Neoplasms -- pathology KW - Papilloma -- genetics KW - Cell Aging -- genetics KW - Gene Expression Regulation, Neoplastic -- genetics KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73432770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Smad3+regulates+senescence+and+malignant+conversion+in+a+mouse+multistage+skin+carcinogenesis+model.&rft.au=Vijayachandra%2C+Kinnimulki%3BLee%2C+Jessica%3BGlick%2C+Adam+B&rft.aulast=Vijayachandra&rft.aufirst=Kinnimulki&rft.date=2003-07-01&rft.volume=63&rft.issue=13&rft.spage=3447&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 - 2003-08-25 N1 - Date created - 2003-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-methyl-D-aspartate glutamate receptors and alcoholism: reward, dependence, treatment, and vulnerability. AN - 73430706; 12804700 AB - This review takes a translational neuroscience perspective on the role of glutamate systems in human ethanol abuse and dependence. Ethanol is a simple molecule with profound effects on many chemical systems in the brain. Glutamate is the primary excitatory neurotransmitter in the brain. Glutamatergic systems are targets for the actions of ethanol via its antagonism of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor and other mechanisms. The modulation of glutamatergic function by ethanol contributes to both euphoric and dysphoric consequences of ethanol intoxication. Adaptations within glutamatergic systems appear to contribute to ethanol tolerance and dependence and to both acute and protracted features of ethanol withdrawal. Perhaps because of the important glutamatergic mediation of the behavioral effects of ethanol, glutamatergic systems appear to contribute to the vulnerability to alcoholism, and novel glutamatergic agents may play a role in the treatment of ethanol abuse and dependence. JF - Pharmacology & therapeutics AU - Krystal, John H AU - Petrakis, Ismene L AU - Mason, Graeme AU - Trevisan, Louis AU - D'Souza, D Cyril AD - NIAAA Center for the Translational Neuroscience of Alcoholism, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA. john.krystal@yale.edu Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 79 EP - 94 VL - 99 IS - 1 SN - 0163-7258, 0163-7258 KW - Receptors, N-Methyl-D-Aspartate KW - 0 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Ethanol -- adverse effects KW - Animals KW - Substance Withdrawal Syndrome -- metabolism KW - Disease Susceptibility KW - Risk Factors KW - Humans KW - Clinical Trials as Topic KW - Alcohol Drinking -- psychology KW - Alcohol Drinking -- adverse effects KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Reward KW - Receptors, N-Methyl-D-Aspartate -- drug effects KW - Alcoholism -- therapy KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Alcoholism -- metabolism KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73430706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%26+therapeutics&rft.atitle=N-methyl-D-aspartate+glutamate+receptors+and+alcoholism%3A+reward%2C+dependence%2C+treatment%2C+and+vulnerability.&rft.au=Krystal%2C+John+H%3BPetrakis%2C+Ismene+L%3BMason%2C+Graeme%3BTrevisan%2C+Louis%3BD%27Souza%2C+D+Cyril&rft.aulast=Krystal&rft.aufirst=John&rft.date=2003-07-01&rft.volume=99&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Pharmacology+%26+therapeutics&rft.issn=01637258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-24 N1 - Date created - 2003-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of genetically altered mice for breast cancer prevention studies. AN - 73430387; 12840216 AB - Chemoprevention through nutritional and dietary changes may offer an important means of inhibiting the development and progression of breast cancer, which would have a major impact on public health. Studies to assess the efficacy of potential chemopreventive compounds are difficult to perform in large human populations, whereas the use of genetically engineered mice (GEM) for preclinical testing offers several advantages. GEM models can be utilized to assess the inhibitory effects of nutritional and chemopreventive agents on well-defined oncogenic signaling pathways. Because several transgenic mouse models progress through a well-defined temporal series of stages leading to invasive carcinoma formation, they may be particularly useful for determining cancer stage-specific responses to nutritional and chemopreventive agents. The C3(1)SV40 T/t-antigen transgenic mouse mammary cancer model has been utilized for chemopreventive research in which mammary tumors develop over a well-characterized time course. Several compounds have been shown to inhibit mammary tumor development in this model, including retinoids, di-fluoromethylornithine (DFMO), dehydroepiandrosterone (DHEA), antiangiogenic compounds and nonsteroidal antiinflammatory drugs (NSAID). All of the chemopreventive agents used in the C3(1)Tag mammary mouse model appear to affect the promotion stage of tumorigenesis, suggesting that these agents may be useful in inhibiting the transition of human ductal carcinoma in situ (DCIS) to invasive carcinoma. Selective combinations of chemopreventive agents may be particularly useful for targeting multiple signaling pathways involved in cancer development and progression leading to improved clinical responses. The application of gene expression profiling to chemopreventive studies will aid in the selection of appropriate models for preclinical testing and further define mechanisms of action. JF - The Journal of nutrition AU - Kavanaugh, Claudine AU - Green, Jeffrey E AD - Laboratory of Cellular Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 2404S EP - 2409S VL - 133 IS - 7 Suppl SN - 0022-3166, 0022-3166 KW - Index Medicus KW - Animals KW - Chemoprevention -- methods KW - Disease Models, Animal KW - Mice KW - Carcinoma, Intraductal, Noninfiltrating -- prevention & control KW - Mice, Transgenic KW - Mammary Neoplasms, Animal -- genetics KW - Mammary Neoplasms, Animal -- prevention & control KW - Diet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73430387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=The+use+of+genetically+altered+mice+for+breast+cancer+prevention+studies.&rft.au=Kavanaugh%2C+Claudine%3BGreen%2C+Jeffrey+E&rft.aulast=Kavanaugh&rft.aufirst=Claudine&rft.date=2003-07-01&rft.volume=133&rft.issue=7+Suppl&rft.spage=2404S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-06 N1 - Date created - 2003-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reinstatement of punishment-suppressed opioid self-administration in rats: an alternative model of relapse to drug abuse. AN - 73427798; 12845420 AB - Animal models of relapse to drug abuse typically assess the ability of various manipulations to reinstate responding that has ceased due to non-reinforcement (extinction). However, there is a lack of information concerning the reinstatement of responding that has ceased for reasons other than extinction. This study examined the ability of response-independent reinforcer delivery (priming) to reinstate food- or drug-reinforced responding that had been suppressed by response-contingent footshock (punishment). Nose-poke responding by separate groups of rats was reinforced with food (45 mg/delivery) or intravenous remifentanil (4 micro g/kg per infusion), a short-acting micro -opioid agonist. After either 3 or 27 days of training (with 100 reinforcers/day), a punishment contingency was introduced that rapidly suppressed responding. Then, the punishment contingency was discontinued, and half the rats received priming. Priming by non-contingent delivery of food or remifentanil significantly reduced the number of sessions required for responding to resume. There were no significant differences in this effect between short-term and long-term training or between food- and drug-trained groups. Self-administration responding that has been suppressed by punishment can be reinstated by priming, and it can eventually resume even without priming. Under the conditions studied here, priming after punishment had effects qualitatively similar to those typically seen after extinction. This punishment/reinstatement procedure may be useful for comparing the effects of other manipulations known to affect behavior in the extinction/reinstatement model of relapse. JF - Psychopharmacology AU - Panlilio, Leigh V AU - Thorndike, Eric B AU - Schindler, Charles W AD - Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 229 EP - 235 VL - 168 IS - 1-2 SN - 0033-3158, 0033-3158 KW - Analgesics, Opioid KW - 0 KW - Piperidines KW - remifentanil KW - P10582JYYK KW - Index Medicus KW - Rats KW - Piperidines -- pharmacology KW - Animals KW - Self Administration KW - Rats, Long-Evans KW - Secondary Prevention KW - Male KW - Analgesics, Opioid -- pharmacology KW - Disease Models, Animal KW - Punishment -- psychology KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73427798?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reinstatement+of+punishment-suppressed+opioid+self-administration+in+rats%3A+an+alternative+model+of+relapse+to+drug+abuse.&rft.au=Panlilio%2C+Leigh+V%3BThorndike%2C+Eric+B%3BSchindler%2C+Charles+W&rft.aulast=Panlilio&rft.aufirst=Leigh&rft.date=2003-07-01&rft.volume=168&rft.issue=1-2&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-18 N1 - Date created - 2003-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tolerability of azithromycin as malaria prophylaxis in adults in northeast papua, indonesia. AN - 73425741; 12821468 AB - Drug tolerability affects compliance. We evaluated the tolerability levels of azithromycin (750-mg loading dose plus 250 mg/day; n = 148 subjects), doxycycline (100 mg/day; n = 75), and placebo (n = 77) as prophylaxis against malaria in Indonesian adults over 20 weeks. Self-reported and elicited symptoms, health perception, hearing, hematology, and biochemistry were assessed. The loading dose was well tolerated. The frequencies (number per person-years [p-yr]) of all daily reported symptoms were similar in the three arms of the study: 40.2/p-yr for azithromycin, 39.7/p-yr for doxycycline, and 38.2/p-yr for placebo. Relative to those who received placebo, azithromycin recipients complained more often of heartburn (rate ratio = 10.5 [95% confidence interval, 2.8 to 88.1]), paresthesia (2.03 [1.08 to 4.24]), and mild (1.55 [1.01 to 2.48]) and severe (11.2 [1.34 to infinity ]) itching but less often of fever (0.21 [0.09 to 0.49]) and tinnitus (0.09 [0.04 to 0.21]). Azithromycin recipients showed no evidence of clinical hearing loss or hematologic, hepatic, or renal toxicity. One azithromycin recipient developed an erythematous rash. Daily azithromycin was well tolerated by these Indonesian adults during 20 weeks of treatment. JF - Antimicrobial agents and chemotherapy AU - Taylor, Walter R AU - Richie, Thomas L AU - Fryauff, David J AU - Ohrt, Colin AU - Picarima, Helena AU - Tang, Douglas AU - Murphy, Gerald S AU - Widjaja, Hendra AU - Braitman, David AU - Tjitra, Emiliana AU - Ganjar, Asep AU - Jones, Trevor R AU - Basri, Hasan AU - Berman, Josh AD - U.S. Naval Medical Research Unit No 2 , National Institutes of Health, Jakarta, Indonesia. taylorw@who.ch Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 2199 EP - 2203 VL - 47 IS - 7 SN - 0066-4804, 0066-4804 KW - Anti-Bacterial Agents KW - 0 KW - Azithromycin KW - 83905-01-5 KW - Index Medicus KW - Patient Compliance KW - Humans KW - Adult KW - Surveys and Questionnaires KW - Indonesia KW - Male KW - Female KW - Malaria, Falciparum -- prevention & control KW - Anti-Bacterial Agents -- adverse effects KW - Anti-Bacterial Agents -- administration & dosage KW - Azithromycin -- adverse effects KW - Azithromycin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73425741?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tolerability+of+azithromycin+as+malaria+prophylaxis+in+adults+in+northeast+papua%2C+indonesia.&rft.au=Taylor%2C+Walter+R%3BRichie%2C+Thomas+L%3BFryauff%2C+David+J%3BOhrt%2C+Colin%3BPicarima%2C+Helena%3BTang%2C+Douglas%3BMurphy%2C+Gerald+S%3BWidjaja%2C+Hendra%3BBraitman%2C+David%3BTjitra%2C+Emiliana%3BGanjar%2C+Asep%3BJones%2C+Trevor+R%3BBasri%2C+Hasan%3BBerman%2C+Josh&rft.aulast=Taylor&rft.aufirst=Walter&rft.date=2003-07-01&rft.volume=47&rft.issue=7&rft.spage=2199&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 - 2003-08-14 N1 - Date created - 2003-06-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Ann Otol Rhinol Laryngol. 2000 Apr;109(4):435-7 [10778901] Clin Infect Dis. 1997 Jan;24(1):76-7 [8994766] Am J Med. 1997 Feb;102(2):217-8 [9217574] Lancet. 1997 Aug 23;350(9077):563 [9284783] Clin Infect Dis. 1998 Jan;26(1):146-50 [9455524] Clin Infect Dis. 1998 Mar;26(3):611-9 [9524832] BMJ. 1998 Apr 18;316(7139):1236-8 [9553006] Clin Infect Dis. 1999 Jan;28(1):74-81 [10028075] J Antimicrob Chemother. 2001 Apr;47(4):441-6 [11266417] Am J Epidemiol. 1974 Sep;100(3):165-7 [4412586] Am J Dig Dis. 1977 Sep;22(9):805-7 [900095] Stat Med. 1990 Dec;9(12):1447-54 [2281232] Am J Med. 1991 Sep 12;91(3A):40S-45S [1656742] N Engl J Med. 1992 Sep 24;327(13):921-5 [1325036] Lancet. 1993 Aug 21;342(8869):453-6 [8102427] Lancet. 1994 Jan 22;343(8891):241 [7904701] Infect Dis Clin North Am. 1995 Sep;9(3):731-45 [7490441] BMJ. 1996 Feb 10;312(7027):364-7 [8611837] N Engl J Med. 1996 Aug 8;335(6):392-8 [8676932] J Antimicrob Chemother. 1996 Jun;37 Suppl C:143-9 [8818855] Clin Infect Dis. 1996 Nov;23(5):983-9 [8922790] Clin Infect Dis. 1997 May;24(5):958-64 [9142801] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis. AN - 73423395; 12839937 AB - Nickel is a potent environmental pollutant in industrial countries. Because nickel compounds are carcinogenic, exposure to nickel represents a serious hazard to human health. The understanding of how nickel exerts its toxic and carcinogenic effects at a molecular level may be important in risk assessment, as well as in the treatment and prevention of occupational diseases. Previously, using human and rodent cells in vitro, we showed that hypoxia-inducible signaling pathway was activated by carcinogenic nickel compounds. Acute exposure to nickel resulted in the accumulation of hypoxia-inducible transcription factor (HIF)-1, which strongly activated hypoxia-inducible genes, including the recently discovered tumor marker NDRG1 (Cap43). To further identify HIF-1-dependent nickel-inducible genes and to understand the role of the HIF-dependent signaling pathway in nickel-induced transformation, we used the Affymetrix GeneChip to compare the gene expression profiles in wild-type cells or in cells from HIF-1 alpha knockout mouse embryos exposed to nickel chloride. As expected, when we examined 12,000 genes for expression changes, we found that genes coding for glycolytic enzymes and glucose transporters, known to be regulated by HIF-1 transcription factor, were induced by nickel only in HIF-1 alpha-proficient cells. In addition, we found a number of other hypoxia-inducible genes up-regulated by nickel in a HIF-dependent manner including BCL-2-binding protein Nip3, EGLN1, hypoxia-inducible gene 1 (HIG1), and prolyl 4-hydroxylase. Additionally, we found a number of genes induced by nickel in a HIF-independent manner, suggesting that Ni activated other signaling pathways besides HIF-1. Finally, we found that in HIF-1 alpha knockout cells, nickel strongly induced the expression of the whole group of genes that were not expressed in the presence of HIF-1. Because the majority of modulated genes were induced or suppressed by nickel in a HIF-1-dependent manner, we elucidated the role of HIF-1 transcription factor in cell transformation. In HIF-1 alpha-proficient cells, nickel exposure increased soft agar growth, whereas it decreased soft agar growth in HIF-1 alpha-deficient cells. We hypothesize that the induction of HIF-1 transcription factor by nickel may be important during the nickel-induced carcinogenic process. JF - Cancer research AU - Salnikow, Konstantin AU - Davidson, Todd AU - Zhang, Qunwei AU - Chen, Lung Chi AU - Su, Weichen AU - Costa, Max AD - The Nelson Institute of Environmental Medicine, National Institute of Environmental Health Sciences Center, National Institutes of Health and The New York University Cancer Institute, School of Medicine, New York, NY 10016, USA. salnikow@env.med.nyu.edu Y1 - 2003/07/01/ PY - 2003 DA - 2003 Jul 01 SP - 3524 EP - 3530 VL - 63 IS - 13 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - DNA-Binding Proteins KW - Hif1a protein, mouse KW - Hypoxia-Inducible Factor 1 KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Nuclear Proteins KW - Transcription Factors KW - nickel chloride KW - 696BNE976J KW - Nickel KW - 7OV03QG267 KW - Index Medicus KW - Animals KW - Helix-Loop-Helix Motifs KW - Oligonucleotide Array Sequence Analysis KW - Cell Transformation, Neoplastic -- drug effects KW - Mice KW - Cell Line KW - Mice, Knockout KW - Nuclear Proteins -- deficiency KW - Nuclear Proteins -- genetics KW - DNA-Binding Proteins -- deficiency KW - DNA-Binding Proteins -- genetics KW - Carcinogens -- toxicity KW - Nickel -- toxicity KW - DNA-Binding Proteins -- physiology KW - Nuclear Proteins -- physiology KW - Gene Expression Regulation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73423395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+involvement+of+hypoxia-inducible+transcription+factor-1-dependent+pathway+in+nickel+carcinogenesis.&rft.au=Salnikow%2C+Konstantin%3BDavidson%2C+Todd%3BZhang%2C+Qunwei%3BChen%2C+Lung+Chi%3BSu%2C+Weichen%3BCosta%2C+Max&rft.aulast=Salnikow&rft.aufirst=Konstantin&rft.date=2003-07-01&rft.volume=63&rft.issue=13&rft.spage=3524&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 - 2003-08-25 N1 - Date created - 2003-07-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The influenza A virus PB1-F2 protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function. AN - 73422206; 12805420 AB - The 11th influenza A virus gene product is an 87-amino-acid protein provisionally named PB1-F2 (because it is encoded by an open reading frame overlapping the PB1 open reading frame). A significant fraction of PB1-F2 localizes to the inner mitochondrial membrane in influenza A virus-infected cells. PB1-F2 appears to enhance virus-induced cell death in a cell type-dependent manner. For the present communication we have identified and characterized a region near the COOH terminus of PB1-F2 that is necessary and sufficient for its inner mitochondrial membrane localization, as determined by transient expression of chimeric proteins consisting of elements of PB1-F2 genetically fused to enhanced green fluorescent protein (EGFP) in HeLa cells. Targeting of EGFP to mitochondria by this sequence resulted in the loss of the inner mitochondrial membrane potential, leading to cell death. The mitochondrial targeting sequence (MTS) is predicted to form a positively charged amphipathic alpha-helix and, as such, is similar to the MTS of the p13(II) protein of human T-cell leukemia virus type 1. We formally demonstrate the functional interchangeability of the two sequences for mitochondrial localization of PB1-F2. Mutation analysis of the putative amphipathic helix in the PB1-F2 reveals that replacement of five basic amino acids with Ala abolishes mitochondrial targeting, whereas mutation of two highly conserved Leu to Ala does not. These findings demonstrate that PB1-F2 possesses an MTS similar to other viral proteins and that this MTS, when fused to EGFP, is capable of independently compromising mitochondrial function and cellular viability. JF - Journal of virology AU - Gibbs, James S AU - Malide, Daniela AU - Hornung, Felicita AU - Bennink, Jack R AU - Yewdell, Jonathan W AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 7214 EP - 7224 VL - 77 IS - 13 SN - 0022-538X, 0022-538X KW - DNA Primers KW - 0 KW - Luminescent Proteins KW - Recombinant Fusion Proteins KW - Viral Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Index Medicus KW - HeLa Cells KW - Humans KW - Amino Acid Sequence KW - Luminescent Proteins -- metabolism KW - Plasmids KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Intracellular Membranes -- virology KW - Base Sequence KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Intracellular Membranes -- physiology KW - Sequence Homology, Amino Acid KW - Luminescent Proteins -- genetics KW - Viral Proteins -- genetics KW - Influenza A virus -- physiology KW - Viral Proteins -- chemistry KW - Viral Proteins -- metabolism KW - Viral Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73422206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=The+influenza+A+virus+PB1-F2+protein+targets+the+inner+mitochondrial+membrane+via+a+predicted+basic+amphipathic+helix+that+disrupts+mitochondrial+function.&rft.au=Gibbs%2C+James+S%3BMalide%2C+Daniela%3BHornung%2C+Felicita%3BBennink%2C+Jack+R%3BYewdell%2C+Jonathan+W&rft.aulast=Gibbs&rft.aufirst=James&rft.date=2003-07-01&rft.volume=77&rft.issue=13&rft.spage=7214&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-01 N1 - Date created - 2003-06-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 2000 Jan 3;191(1):33-46 [10620603] Oncogene. 1999 Aug 5;18(31):4505-14 [10442641] J Biol Chem. 2001 Apr 6;276(14):11317-22 [11133991] EMBO J. 2001 Aug 15;20(16):4325-31 [11500358] Nat Med. 2001 Dec;7(12):1306-12 [11726970] Mol Biol Cell. 2002 May;13(5):1439-48 [12006643] Biochimie. 2002 Feb-Mar;84(2-3):113-21 [12022942] J Virol. 2002 Aug;76(15):7843-54 [12097596] J Cell Physiol. 2002 Aug;192(2):131-7 [12115719] Biochim Biophys Acta. 2002 Sep 2;1592(1):3-14 [12191763] J Biol Chem. 2002 Sep 13;277(37):34424-33 [12093802] Cell Death Differ. 2002 Nov;9(11):1212-9 [12404120] Methods Enzymol. 1996;266:525-39 [8743704] EMBO J. 1996 Aug 15;15(16):4246-53 [8861953] J Biol Chem. 1997 Aug 15;272(33):20730-5 [9252394] Biophys J. 1999 Jan;76(1 Pt 1):469-77 [9876159] AIDS Res Hum Retroviruses. 2000 Nov 1;16(16):1765-70 [11080824] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetic and pharmacodynamic effects of oral eniluracil, fluorouracil and leucovorin given on a weekly schedule. AN - 73421884; 12707718 AB - To determine the toxicities and pharmacokinetic effects of eniluracil (EU) given on two weekly dosing schedules with 5-fluorouracil (5-FU) and leucovorin (LV). A group of 26 patients received a single 24-h i.v. infusion of 5-FU 2300 mg/m(2) to provide a pharmacokinetic reference. After 2 weeks, patients received oral EU 20 mg plus LV 30 mg on days 1-3 with a single dose of 5-FU 15-29 mg/m(2) on day 2, or LV 30 mg on days 1-2 with a single dose of EU at least 1 h prior to 5-FU 29 mg/m(2) on day 2 weekly for 3 of 4 weeks. Diarrhea was the most common dose-limiting toxicity. The recommended dose of 5-FU is 29 mg/m(2) per day. EU on either schedule decreased 5-FU plasma clearance by 48 to 52-fold, prolonged the half-life to >5 h, and increased the percentage of 5-FU excreted in the urine from 2% to 64-66%. With EU, plasma fluoro-beta-alanine was not detected while urinary excretion was reduced to <1% of that seen with i.v. 5-FU alone. Marked increases in both plasma and urinary uracil were seen. Thymidylate synthase ternary complex formation was demonstrated in bone marrow mononuclear cells isolated 24 h after the first oral 5-FU dose; the average was 66.5% bound. Either a single 20-mg dose of EU given prior to or for 3 days around the oral 5-FU dose led to comparable effects on 5-FU pharmacokinetic parameters, and inhibition of dihydropyrimidine dehydrogenase and thymidylate synthase. JF - Cancer chemotherapy and pharmacology AU - Guo, Xiao-Du AU - Harold, Nancy AU - Saif, M Wasif AU - Schuler, Barbara AU - Szabo, Eva AU - Hamilton, J Michael AU - Monahan, Brian P AU - Quinn, Mary G AU - Cliatt, Janet AU - Nguyen, Diana AU - Grollman, Frank AU - Thomas, Rebecca R AU - McQuigan, Elizabeth A AU - Wilson, Richard AU - Takimoto, Chis H AU - Grem, Jean L AD - National Cancer Institute-Navy Medical Oncology, Cancer Therapeutics Branch, Center for Cancer Research, National Naval Medical Center, Bethesda, MD 20889-5105, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 79 EP - 85 VL - 52 IS - 1 SN - 0344-5704, 0344-5704 KW - Antimetabolites, Antineoplastic KW - 0 KW - Enzyme Inhibitors KW - eniluracil KW - 2E2W0W5XIU KW - Uracil KW - 56HH86ZVCT KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Administration, Oral KW - Infusions, Intravenous KW - Half-Life KW - Area Under Curve KW - Humans KW - Adult KW - Metabolic Clearance Rate KW - Aged KW - Middle Aged KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Uracil -- therapeutic use KW - Enzyme Inhibitors -- therapeutic use KW - Uracil -- analogs & derivatives KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Uracil -- pharmacology KW - Antimetabolites, Antineoplastic -- pharmacology KW - Fluorouracil -- therapeutic use KW - Enzyme Inhibitors -- pharmacokinetics KW - Enzyme Inhibitors -- pharmacology KW - Fluorouracil -- pharmacology KW - Leucovorin -- pharmacology KW - Fluorouracil -- pharmacokinetics KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Uracil -- pharmacokinetics KW - Neoplasms -- metabolism KW - Leucovorin -- pharmacokinetics KW - Leucovorin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73421884?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+chemotherapy+and+pharmacology&rft.atitle=Pharmacokinetic+and+pharmacodynamic+effects+of+oral+eniluracil%2C+fluorouracil+and+leucovorin+given+on+a+weekly+schedule.&rft.au=Guo%2C+Xiao-Du%3BHarold%2C+Nancy%3BSaif%2C+M+Wasif%3BSchuler%2C+Barbara%3BSzabo%2C+Eva%3BHamilton%2C+J+Michael%3BMonahan%2C+Brian+P%3BQuinn%2C+Mary+G%3BCliatt%2C+Janet%3BNguyen%2C+Diana%3BGrollman%2C+Frank%3BThomas%2C+Rebecca+R%3BMcQuigan%2C+Elizabeth+A%3BWilson%2C+Richard%3BTakimoto%2C+Chis+H%3BGrem%2C+Jean+L&rft.aulast=Guo&rft.aufirst=Xiao-Du&rft.date=2003-07-01&rft.volume=52&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Cancer+chemotherapy+and+pharmacology&rft.issn=03445704&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-26 N1 - Date created - 2003-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maintenance therapy with ribavirin in patients with chronic hepatitis C who fail to respond to combination therapy with interferon alfa and ribavirin. AN - 73420580; 12829988 AB - To assess the efficacy and safety of maintenance therapy with ribavirin alone in chronic hepatitis C, 108 patients were treated with the combination of interferon alfa and ribavirin for 24 weeks; those who failed to have a virologic response were offered enrollment in a randomized, double-blind, controlled trial of ribavirin (1,000-1,200 mg daily) versus placebo for the subsequent 48 weeks. Patients were monitored at regular intervals with symptom questionnaires, serum aminotransferase levels, hepatitis C virus (HCV) RNA levels, and complete blood counts and underwent liver biopsy at the completion of therapy. Among 108 patients, 50 were still HCV RNA positive after 24 weeks of treatment, of whom 34 agreed to be randomized to continue either ribavirin monotherapy or placebo. Among 17 patients who received placebo, there was no overall improvement in symptoms, serum alanine aminotransferase (ALT) levels, HCV RNA levels, or hepatic histology. Among the 17 patients who received ribavirin, serum ALT levels and necroinflammatory features of liver histology were improved, whereas symptoms, HCV RNA levels, and hepatic fibrosis scores were not changed significantly from baseline. Responses to ribavirin seemed to be categorical, such that 8 patients (47%) had definite improvement in liver histology. Patients with improved histology had improvements in serum ALT levels both on combination therapy and after switching to ribavirin monotherapy. In conclusion, continuation of ribavirin monotherapy may maintain serum biochemical improvements that occur during interferon-ribavirin combination therapy in some patients and that these improvements are often associated with decreases in necroinflammatory changes in the liver. Whether these improvements will ultimately result in prevention of progression of hepatitis C requires further study. JF - Hepatology (Baltimore, Md.) AU - Hoofnagle, Jay H AU - Ghany, Marc G AU - Kleiner, David E AU - Doo, Edward AU - Heller, Theo AU - Promrat, Kittichai AU - Ong, Janus AU - Khokhar, Farooq AU - Soza, Alejandro AU - Herion, David AU - Park, Yoon AU - Everhart, James E AU - Liang, T Jake AD - Liver Diseases Section, Digestive Diseases Branch, and Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Hoofnalej@extra.niddk.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 66 EP - 74 VL - 38 IS - 1 SN - 0270-9139, 0270-9139 KW - Antiviral Agents KW - 0 KW - Interferon-alpha KW - RNA, Viral KW - Ribavirin KW - 49717AWG6K KW - Index Medicus KW - Drug Therapy, Combination KW - Liver -- pathology KW - Drug Resistance, Viral KW - Double-Blind Method KW - Humans KW - Middle Aged KW - Biopsy KW - Male KW - Female KW - RNA, Viral -- analysis KW - Antiviral Agents -- administration & dosage KW - Interferon-alpha -- adverse effects KW - Interferon-alpha -- administration & dosage KW - Hepacivirus -- genetics KW - Hepatitis C, Chronic -- drug therapy KW - Ribavirin -- administration & dosage KW - Antiviral Agents -- adverse effects KW - Hepacivirus -- drug effects KW - Ribavirin -- adverse effects KW - Hepatitis C, Chronic -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73420580?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Maintenance+therapy+with+ribavirin+in+patients+with+chronic+hepatitis+C+who+fail+to+respond+to+combination+therapy+with+interferon+alfa+and+ribavirin.&rft.au=Hoofnagle%2C+Jay+H%3BGhany%2C+Marc+G%3BKleiner%2C+David+E%3BDoo%2C+Edward%3BHeller%2C+Theo%3BPromrat%2C+Kittichai%3BOng%2C+Janus%3BKhokhar%2C+Farooq%3BSoza%2C+Alejandro%3BHerion%2C+David%3BPark%2C+Yoon%3BEverhart%2C+James+E%3BLiang%2C+T+Jake&rft.aulast=Hoofnagle&rft.aufirst=Jay&rft.date=2003-07-01&rft.volume=38&rft.issue=1&rft.spage=66&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-25 N1 - Date created - 2003-06-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Hepatology. 2003 Jul;38(1):21-4 [12829982] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peritoneal mesothelioma treated by induction chemotherapy, cytoreductive surgery, and intraperitoneal hyperthermic perfusion. AN - 73420284; 12827682 AB - Peritoneal mesothelioma (PM) is a rare disease, with a poor prognosis. We decided to prospectively evaluate the prognostic impact of aggressive surgery followed by intraperitoneal chemotherapy with local hyperthermia. In this prospective study, 19 patients with PM were treated by cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). Mean follow-up was 27 months (range: 1-65). Fifteen (68%) patients had malignant disease, two had well-differentiated papillary mesothelioma, and two had multicystic PM. Thirteen (65%) patients received preoperative chemotherapy. Fifteen cases (75%) underwent optimal cytoreduction (residual disease <2.5 mm). One patient underwent the procedure twice due to locoregional progression. IPHP was performed with closed abdomen technique, using a preheated polysaline perfusate (42.5 degrees C) containing cisplatin + mitomycin C or cisplatin + doxorubicin administered through a heart-lung pump for 60 or 90 min. Three-year overall and progression-free survival was 69 and 66%, respectively. The operative morbidity (grade II/III), mortality, and overall toxicity (grade I-IV) rates were 25, 0, and 30%, respectively. Seventeen (94%) out of 18 patients had resolution of ascites. This therapeutic strategy proved feasible and was well tolerated. Early results seem promising and consistent with a potentially major impact on survival in selected patients with PM. Copyright 2003 Wiley-Liss, Inc. JF - Journal of surgical oncology AU - Deraco, Marcello AU - Casali, Paolo AU - Inglese, M G AU - Baratti, Dario AU - Pennacchioli, Elisabetta AU - Bertulli, Rossella AU - Kusamura, Shigeki AD - Department of Surgery, National Cancer Institute of Milan, Milan, Italy. marcello.deraco@istitutotumori.mi.it Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 147 EP - 153 VL - 83 IS - 3 SN - 0022-4790, 0022-4790 KW - Mitomycin KW - 50SG953SK6 KW - Doxorubicin KW - 80168379AG KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Combined Modality Therapy KW - Humans KW - Aged KW - Doxorubicin -- administration & dosage KW - Infusions, Parenteral KW - Mitomycin -- administration & dosage KW - Drug Administration Routes KW - Cisplatin -- administration & dosage KW - Prospective Studies KW - Adult KW - Middle Aged KW - Female KW - Male KW - Survival Analysis KW - Mesothelioma -- therapy KW - Mesothelioma -- drug therapy KW - Mesothelioma -- surgery KW - Peritoneal Neoplasms -- surgery KW - Peritoneal Neoplasms -- drug therapy KW - Hyperthermia, Induced -- methods KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Peritoneal Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73420284?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+surgical+oncology&rft.atitle=Peritoneal+mesothelioma+treated+by+induction+chemotherapy%2C+cytoreductive+surgery%2C+and+intraperitoneal+hyperthermic+perfusion.&rft.au=Deraco%2C+Marcello%3BCasali%2C+Paolo%3BInglese%2C+M+G%3BBaratti%2C+Dario%3BPennacchioli%2C+Elisabetta%3BBertulli%2C+Rossella%3BKusamura%2C+Shigeki&rft.aulast=Deraco&rft.aufirst=Marcello&rft.date=2003-07-01&rft.volume=83&rft.issue=3&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Journal+of+surgical+oncology&rft.issn=00224790&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-25 N1 - Date created - 2003-06-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cadmium is a mutagen that acts by inhibiting mismatch repair. AN - 73419109; 12796780 AB - Most errors that arise during DNA replication can be corrected by DNA polymerase proofreading or by post-replication mismatch repair (MMR). Inactivation of both mutation-avoidance systems results in extremely high mutability that can lead to error catastrophe. High mutability and the likelihood of cancer can be caused by mutations and epigenetic changes that reduce MMR. Hypermutability can also be caused by external factors that directly inhibit MMR. Identifying such factors has important implications for understanding the role of the environment in genome stability. We found that chronic exposure of yeast to environmentally relevant concentrations of cadmium, a known human carcinogen, can result in extreme hypermutability. The mutation specificity along with responses in proofreading-deficient and MMR-deficient mutants indicate that cadmium reduces the capacity for MMR of small misalignments and base-base mismatches. In extracts of human cells, cadmium inhibited at least one step leading to mismatch removal. Together, our data show that a high level of genetic instability can result from environmental impediment of a mutation-avoidance system. JF - Nature genetics AU - Jin, Yong Hwan AU - Clark, Alan B AU - Slebos, Robbert J C AU - Al-Refai, Hanan AU - Taylor, Jack A AU - Kunkel, Thomas A AU - Resnick, Michael A AU - Gordenin, Dmitry A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 326 EP - 329 VL - 34 IS - 3 SN - 1061-4036, 1061-4036 KW - DNA, Fungal KW - 0 KW - Mutagens KW - Cadmium KW - 00BH33GNGH KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Mitosis KW - Kinetics KW - Genome KW - DNA Replication -- drug effects KW - DNA-Directed DNA Polymerase -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - Cadmium -- toxicity KW - Mutagens -- toxicity KW - DNA, Fungal -- drug effects KW - Base Pair Mismatch -- drug effects KW - DNA Repair -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73419109?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genetics&rft.atitle=Cadmium+is+a+mutagen+that+acts+by+inhibiting+mismatch+repair.&rft.au=Jin%2C+Yong+Hwan%3BClark%2C+Alan+B%3BSlebos%2C+Robbert+J+C%3BAl-Refai%2C+Hanan%3BTaylor%2C+Jack+A%3BKunkel%2C+Thomas+A%3BResnick%2C+Michael+A%3BGordenin%2C+Dmitry+A&rft.aulast=Jin&rft.aufirst=Yong&rft.date=2003-07-01&rft.volume=34&rft.issue=3&rft.spage=326&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-01 N1 - Date created - 2003-06-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Toxicol Appl Pharmacol. 1997 Jun;144(2):247-61 [9194408] Mol Cell Biol. 1999 Mar;19(3):2000-7 [10022887] Mutat Res. 1998 May 25;400(1-2):45-58 [9685581] Mol Cell Biol. 1999 Aug;19(8):5373-82 [10409728] Curr Biol. 1999 Aug 26;9(16):907-10 [10469597] Anticancer Res. 1999 Nov-Dec;19(6A):4645-64 [10697584] Genetics. 2000 Oct;156(2):571-8 [11014807] Annu Rev Genet. 2000;34:359-399 [11092832] Hum Mol Genet. 2001 Apr;10(7):735-40 [11257106] Science. 2001 Mar 30;291(5513):2606-8 [11283373] Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5122-7 [11309502] Antioxid Redox Signal. 2001 Aug;3(4):625-34 [11554449] Mol Cell. 2002 Apr;9(4):713-23 [11983164] Hum Mol Genet. 2002 May 15;11(11):1351-62 [12019217] Annu Rev Biochem. 2002;71:133-63 [12045093] Curr Opin Urol. 2002 Sep;12(5):407-11 [12172428] Science. 1976 Dec 24;194(4272):1434-6 [1006310] EMBO J. 1993 Apr;12(4):1467-73 [8385605] J Biol Chem. 1993 Nov 15;268(32):23762-5 [8226906] Mol Gen Genet. 1994 Feb;242(3):289-96 [8107676] IARC Monogr Eval Carcinog Risks Hum. 1993;58:119-237 [8022055] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9871-5 [7937908] Biochemistry. 1996 Jan 23;35(3):1046-53 [8547240] Genes Dev. 1996 Feb 15;10(4):407-20 [8600025] Cell. 1996 Oct 4;87(1):65-73 [8858149] Mol Cell Biol. 1997 May;17(5):2859-65 [9111358] Comment In: Nat Genet. 2003 Jul;34(3):239-41 [12833042] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of discoidin domain receptor 1 isoform b (DDR1b) with collagen activates p38 mitogen-activated protein kinase and promotes differentiation of macrophages. AN - 73418964; 12738814 AB - Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagen. DDR1 is constitutively expressed in a variety of normal and transformed epithelial cells and plays a role in cell migration and differentiation through as yet unidentified signaling pathways. We previously reported inducible expression of DDR1 in human leukocytes and suggested a role for the DDR1a isoform in leukocyte migration through extracellular matrix. Here, we evaluated the contribution of DDR1 in the differentiation of the human monocytic THP-1 cells overexpressing these isoforms and of primary macrophages. Interestingly, collagen activation of DDR1b, but not DDR1a, further promoted phorbol ester-induced differentiation of THP-1 cells as determined by reduced cell proliferation and up-regulated expression of HLA-DR, CD11c, CD14, and CD40. Collagen activation of DDR1b also induced the recruitment and phosphorylation of Shc and subsequent phosphorylation of p38 mitogen-activated protein (MAP) kinase and its substrate ATF2. A p38 MAP kinase inhibitor, SB203580, completely inhibited DDR1b-mediated HLA-DR expression. Activation of DDR1 endogenously expressed on macrophages also up-regulated their HLA-DR expression in a p38 MAP kinase-dependent manner. Thus, DDR1b in response to collagen transduces signals that promote maturation/differentiation of HLA-DR-positive antigen-presenting cells and contributes to the development of adaptive immunity in a tissue microenvironment. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Matsuyama, Wataru AU - Kamohara, Hidenobu AU - Galligan, Carole AU - Faure, Michel AU - Yoshimura, Teizo AD - Laboratory of Molecular Immunoregulation, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 1286 EP - 1288 VL - 17 IS - 10 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Adaptor Proteins, Vesicular Transport KW - HLA-DR Antigens KW - Protein Isoforms KW - Proteins KW - Receptors, Mitogen KW - SHC1 protein, human KW - Shc Signaling Adaptor Proteins KW - Src Homology 2 Domain-Containing, Transforming Protein 1 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Collagen KW - 9007-34-5 KW - Discoidin Domain Receptors KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Enzyme Activation KW - Humans KW - Protein Isoforms -- metabolism KW - Cell Differentiation KW - HLA-DR Antigens -- metabolism KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Proteins -- metabolism KW - MAP Kinase Signaling System KW - Phosphorylation KW - Monocytes -- immunology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line, Transformed KW - Macrophages -- enzymology KW - Macrophages -- immunology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Collagen -- metabolism KW - Receptors, Mitogen -- metabolism KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Macrophages -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73418964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interaction+of+discoidin+domain+receptor+1+isoform+b+%28DDR1b%29+with+collagen+activates+p38+mitogen-activated+protein+kinase+and+promotes+differentiation+of+macrophages.&rft.au=Matsuyama%2C+Wataru%3BKamohara%2C+Hidenobu%3BGalligan%2C+Carole%3BFaure%2C+Michel%3BYoshimura%2C+Teizo&rft.aulast=Matsuyama&rft.aufirst=Wataru&rft.date=2003-07-01&rft.volume=17&rft.issue=10&rft.spage=1286&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-17 N1 - Date created - 2003-06-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Retraction In: FASEB J. 2009 Sep;23(9):3251 [19720626] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interpreting epidemiologic research: lessons from studies of childhood cancer. AN - 73418790; 12837914 JF - Pediatrics AU - Linet, Martha S AU - Wacholder, Sholom AU - Zahm, Shelia Hoar AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7238, USA. linetm@exchange.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 218 EP - 232 VL - 112 IS - 1 Pt 2 KW - Abridged Index Medicus KW - Index Medicus KW - Causality KW - Epidemiologic Methods KW - Risk Factors KW - Humans KW - Child KW - Terminology as Topic KW - Statistics as Topic KW - Meta-Analysis as Topic KW - Neoplasms -- epidemiology KW - Environmental Exposure -- adverse effects KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73418790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Interpreting+epidemiologic+research%3A+lessons+from+studies+of+childhood+cancer.&rft.au=Linet%2C+Martha+S%3BWacholder%2C+Sholom%3BZahm%2C+Shelia+Hoar&rft.aulast=Linet&rft.aufirst=Martha&rft.date=2003-07-01&rft.volume=112&rft.issue=1+Pt+2&rft.spage=218&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=1098-4275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-14 N1 - Date created - 2003-07-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Pediatrics. 2004 Feb;113(2):430-1 [14754972] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence of effects of environmental chemicals on the endocrine system in children. AN - 73411379; 12837917 AB - Pollutant chemicals that are widespread in the environment can affect endocrine signaling, as evidenced in laboratory experiments and in wildlife with relatively high exposures. Although humans are commonly exposed to such pollutant chemicals, the exposures are generally low, and clear effects on endocrine function from such exposures have been difficult to demonstrate. Several instances in which there are data from humans on exposure to the chemical agent and the endocrine outcome are reviewed, including age at weaning, age at puberty, and sex ratio at birth, and the strength of the evidence is discussed. Although endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real. JF - Pediatrics AU - Rogan, Walter J AU - Ragan, N Beth AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. rogan@niehs.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 247 EP - 252 VL - 112 IS - 1 Pt 2 KW - Environmental Pollutants KW - 0 KW - Insecticides KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Abridged Index Medicus KW - Index Medicus KW - Breast Feeding KW - Humans KW - Child KW - Sex Ratio KW - Adolescent KW - Male KW - Female KW - Insecticides -- adverse effects KW - Puberty -- drug effects KW - Endocrine System -- drug effects KW - Dichlorodiphenyl Dichloroethylene -- adverse effects KW - Environmental Pollutants -- adverse effects KW - Polychlorinated Biphenyls -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73411379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Evidence+of+effects+of+environmental+chemicals+on+the+endocrine+system+in+children.&rft.au=Rogan%2C+Walter+J%3BRagan%2C+N+Beth&rft.aulast=Rogan&rft.aufirst=Walter&rft.date=2003-07-01&rft.volume=112&rft.issue=1+Pt+2&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=1098-4275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-14 N1 - Date created - 2003-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of SEN viruses among injection drug users in the San Francisco Bay area. AN - 73410350; 12825166 AB - SEN viruses (SENVs) are newly discovered bloodborne viruses that may play a role in liver disease. SENV strain prevalence was examined in a race/ethnicity-stratified sample of 531 injection drug users (IDUs) from the San Francisco Bay area. Weighted prevalences were as follows: SENV-A, 45.7%; SENV-C/H, 35.6%; and SENV-D, 10.3%. Infection was associated with a longer duration of injection drug use. SENV-A was more common in black subjects (adjusted odds ratio [OR(a)], 4.37; 95% confidence interval [CI], 2.65-7.21) and Hispanic subjects (OR(a), 2.30; 95% CI, 1.38-3.85) than in white and non-Hispanic subjects, and the pattern was similar for SENV-C/H. For SENV-D, prevalence was similar in black and white subjects, but lower in Hispanic subjects; infection was less common among women than men (OR(a), 0.32; 95% CI, 0.15-0.71) and more common among men with at least 1 recent male sex partner than among heterosexual men (OR(a), 7.05; 95% CI, 2.62-18.95). SENV strains are common among San Francisco Bay area IDUs, and prevalence varies demographically within this group. JF - The Journal of infectious diseases AU - Pfeiffer, Ruth M AU - Tanaka, Yasuhito AU - Yeo, Anthony E T AU - Umemura, Takeji AU - Seal, Karen H AU - Shih, J Wai-Kuo AU - Alter, Harvey J AU - Edlin, Brian R AU - O'Brien, Thomas R AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland 20852, USA. Y1 - 2003/07/01/ PY - 2003 DA - 2003 Jul 01 SP - 13 EP - 18 VL - 188 IS - 1 SN - 0022-1899, 0022-1899 KW - DNA, Viral KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - African Americans KW - Aged KW - Hispanic Americans KW - Aged, 80 and over KW - European Continental Ancestry Group KW - Adult KW - DNA, Viral -- blood KW - San Francisco -- epidemiology KW - Middle Aged KW - Female KW - Male KW - Prevalence KW - DNA Virus Infections -- epidemiology KW - Substance Abuse, Intravenous -- virology KW - DNA Virus Infections -- ethnology KW - DNA Virus Infections -- complications KW - Substance Abuse, Intravenous -- ethnology KW - DNA Viruses -- isolation & purification KW - Substance Abuse, Intravenous -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73410350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Prevalence+of+SEN+viruses+among+injection+drug+users+in+the+San+Francisco+Bay+area.&rft.au=Pfeiffer%2C+Ruth+M%3BTanaka%2C+Yasuhito%3BYeo%2C+Anthony+E+T%3BUmemura%2C+Takeji%3BSeal%2C+Karen+H%3BShih%2C+J+Wai-Kuo%3BAlter%2C+Harvey+J%3BEdlin%2C+Brian+R%3BO%27Brien%2C+Thomas+R&rft.aulast=Pfeiffer&rft.aufirst=Ruth&rft.date=2003-07-01&rft.volume=188&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-13 N1 - Date created - 2003-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of beta-carotene 15, 15'-monooxygenase as a peroxisome proliferator-activated receptor target gene. AN - 73405089; 12759335 AB - Beta-carotene 15,15'-monooxygenase (BCM) catalyzes the first step of vitamin A biosynthesis from provitamin A carotenoids. We wished to determine the factors underlying the transcriptional regulation of this gene. After cloning of the 40 kilobase pair (kbp) mouse Bcm gene and determination of its genomic organization, analysis of the 2 kb 5'-flanking region showed several putative transcription factor binding sites including TATA box, a peroxisome proliferator response element (PPRE), AP2, and bHLH. The 2 kb fragment drove specific luciferase gene expression in vitro only in cell lines that express BCM (TC7, PF11, and monkey retinal pigment epithelium). Nucleotides -41 to +163, and -60 to +163 drove basal and specific Bcm transcriptional activity, respectively. Site-directed mutagenesis and gel shift experiments demonstrate that PPRE was essential for Bcm promoter specificity and that the peroxisome proliferator activated receptor (PPAR) gamma (PPARgamma) specifically binds to this element. Furthermore, cotransfection experiments and pharmacological treatments in vitro, using the specific PPARgamma agonists LY17883 and ciglitazone, demonstrate that the PPRE element confers peroxisome proliferator responsiveness via the PPARgamma and retinoid X receptor-alpha heterodimer. Treatment of mice with the PPARalpha/gamma agonist WY14643 increases BCM protein expression in liver. Thus PPAR is a key transcription factor for the transcriptional regulation of the Bcm gene, suggesting a broader function for PPARs in the regulation of carotenoid metabolism metabolism that is consistent with their established role in neutral lipid metabolism and transport. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Boulanger, Ana AU - McLemore, Pamela AU - Copeland, Neal G AU - Gilbert, Debra J AU - Jenkins, Nancy A AU - Yu, Shirley S AU - Gentleman, Susan AU - Redmond, T Michael AD - Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2740, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 1304 EP - 1306 VL - 17 IS - 10 KW - Receptors, Cytoplasmic and Nuclear KW - 0 KW - Transcription Factors KW - Oxygenases KW - EC 1.13.- KW - BCMO1 protein, human KW - EC 1.14.99.36 KW - Bcmo1 protein, mouse KW - beta-Carotene 15,15'-Monooxygenase KW - Index Medicus KW - Animals KW - Models, Genetic KW - Humans KW - Mice KW - Caco-2 Cells KW - Response Elements KW - Cell Line KW - Cloning, Molecular KW - Binding Sites KW - Receptors, Cytoplasmic and Nuclear -- agonists KW - Promoter Regions, Genetic KW - Transcription Factors -- agonists KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Oxygenases -- genetics KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73405089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+beta-carotene+15%2C+15%27-monooxygenase+as+a+peroxisome+proliferator-activated+receptor+target+gene.&rft.au=Boulanger%2C+Ana%3BMcLemore%2C+Pamela%3BCopeland%2C+Neal+G%3BGilbert%2C+Debra+J%3BJenkins%2C+Nancy+A%3BYu%2C+Shirley+S%3BGentleman%2C+Susan%3BRedmond%2C+T+Michael&rft.aulast=Boulanger&rft.aufirst=Ana&rft.date=2003-07-01&rft.volume=17&rft.issue=10&rft.spage=1304&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-17 N1 - Date created - 2003-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of a cDNA microarray to determine molecular mechanisms involved in grey platelet syndrome. AN - 73397012; 12823356 AB - The grey platelet syndrome (GPS) is a bleeding disorder of unknown aetiology with phenotypic and genetic heterogeneity. Affected patients exhibit macrothrombocytopenia, decreased alpha-granule content and, sometimes, myelofibrosis. We used microarray technology to investigate changes in gene expression that might reveal mechanisms involved in GPS. The expression of 4900 unique genes and expressed sequence tags was evaluated in fibroblasts from a GPS patient; normal fibroblasts provided the reference standard. Genes that were differentially regulated in the GPS cells were categorized into gene clusters based upon similarity/differences of expression differences. The results showed that genes with functional similarities clustered together. This analysis revealed significant upregulation of selected biological processes involving the production of cytoskeleton proteins, including fibronectin 1, thrombospondins 1 and 2, and collagen VI alpha. These genes appear to play a role in the pathogenesis of GPS. Indeed, Northern blot analyses confirmed that fibronectin, thrombospondin and matrix metalloprotease-2 were overexpressed in GPS fibroblasts compared with normal fibroblasts. Moreover, immunohistochemistry studies revealed robust fibronectin staining in GPS fibroblasts compared with normal ones. Our findings support the feasibility of using cDNA microarray techniques to detect distinctive and informative differences in gene expression patterns relevant to GPS, and suggest that the molecular basis for myelofibrosis in GPS involves upregulation of cytoskeleton proteins. JF - British journal of haematology AU - Hyman, Tehila AU - Huizing, Marjan AU - Blumberg, Peter M AU - Falik-Zaccai, Tzipora C AU - Anikster, Yair AU - Gahl, William A AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 142 EP - 149 VL - 122 IS - 1 SN - 0007-1048, 0007-1048 KW - Collagen Type VI KW - 0 KW - DNA, Complementary KW - Fibronectins KW - Thrombospondins KW - Index Medicus KW - Blotting, Northern KW - Collagen Type VI -- biosynthesis KW - DNA, Complementary -- genetics KW - Humans KW - Gene Expression KW - Fibroblasts -- metabolism KW - Gene Expression Profiling -- methods KW - Cells, Cultured KW - Syndrome KW - Fibronectins -- biosynthesis KW - Up-Regulation KW - Thrombospondins -- biosynthesis KW - Cluster Analysis KW - Expressed Sequence Tags KW - Oligonucleotide Array Sequence Analysis -- methods KW - Blood Platelet Disorders -- genetics KW - Blood Platelet Disorders -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73397012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+haematology&rft.atitle=Use+of+a+cDNA+microarray+to+determine+molecular+mechanisms+involved+in+grey+platelet+syndrome.&rft.au=Hyman%2C+Tehila%3BHuizing%2C+Marjan%3BBlumberg%2C+Peter+M%3BFalik-Zaccai%2C+Tzipora+C%3BAnikster%2C+Yair%3BGahl%2C+William+A&rft.aulast=Hyman&rft.aufirst=Tehila&rft.date=2003-07-01&rft.volume=122&rft.issue=1&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=British+journal+of+haematology&rft.issn=00071048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-16 N1 - Date created - 2003-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic analysis of the rat lung following elemental mercury vapor exposure. AN - 73393956; 12730625 AB - Elemental mercury (Hg0) is a highly toxic chemical with increasing public health concern. Although the lung receives the highest exposure to Hg0 vapor, it is resistant to Hg0 toxicity relative to the kidney and brain. In an earlier study, exposure of rats to 4 mg Hg0 vapor/m3, 2 h per day for 10 days, did not produce pathological alterations in the lung but increased metallothionein and glutathione S-transferase in the kidney. This study was undertaken to examine pulmonary gene expression associated with Hg0 vapor inhalation. Total RNA was extracted from lung tissues of rats, previously exposed to air or Hg0 vapor, and subjected to microarray analysis. Hg0 vapor exposure increased the expression of genes encoding inflammatory responses, such as chemokines, tumor necrosis factor-alpha (TNFalpha), TNF-receptor-1, interleukin-2 (IL-2), IL-7, prostaglandin E2 receptor, and heat-shock proteins. As adaptive responses, glutathione S-transferases (GST-pi, mGST1), metallothionein, and thioredoxin peroxidase were all increased in response to Hg exposure. Some transporters, such as multidrug resistance-associated protein (MRP), P-glycoprotein, and zinc transporter ZnT1, were also increased in an attempt to reduce pulmonary Hg load. The expression of transcription factor c-jun/AP-1 and PI3-kinases was suppressed, while the expression of protein kinase-C was increased. Expression of epidermal fatty acid-binding protein was also enhanced. Real-time RT-PCR and Western blot analyses confirmed the microarray results. In summary, genomic analysis revealed an array of gene alterations in response to Hg0 vapor exposure, which could be important for the development of pulmonary adaptation to Hg during Hg0 vapor inhalation. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Liu, Jie AU - Lei, Dawei AU - Waalkes, Michael P AU - Beliles, Robert P AU - Morgan, Daniel L AD - Inorganic Carcinogenesis Section, NCI at NIEHS, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 174 EP - 181 VL - 74 IS - 1 SN - 1096-6080, 1096-6080 KW - Antioxidants KW - 0 KW - Carrier Proteins KW - DNA Primers KW - Mercury KW - FXS1BY2PGL KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Rats, Long-Evans KW - Oligonucleotide Array Sequence Analysis KW - Carrier Proteins -- genetics KW - Glutathione -- metabolism KW - Inflammation -- genetics KW - Oxidative Stress -- genetics KW - Reverse Transcriptase Polymerase Chain Reaction KW - Carrier Proteins -- biosynthesis KW - Pregnancy KW - Rats KW - Antioxidants -- metabolism KW - Blotting, Western KW - Signal Transduction -- drug effects KW - Signal Transduction -- genetics KW - Administration, Inhalation KW - Female KW - Gene Expression -- drug effects KW - Lung -- cytology KW - Lung -- drug effects KW - Lung -- metabolism KW - Mercury -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73393956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Genomic+analysis+of+the+rat+lung+following+elemental+mercury+vapor+exposure.&rft.au=Liu%2C+Jie%3BLei%2C+Dawei%3BWaalkes%2C+Michael+P%3BBeliles%2C+Robert+P%3BMorgan%2C+Daniel+L&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2003-07-01&rft.volume=74&rft.issue=1&rft.spage=174&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-02 N1 - Date created - 2003-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The proteasome inhibitor PS-341 sensitizes neoplastic cells to TRAIL-mediated apoptosis by reducing levels of c-FLIP. AN - 73391358; 12637321 AB - Because of the pivotal role the proteasome plays in apoptosis, inhibitors of this enzyme, such as PS-341, provide a great opportunity for exploring synergy between proteasome inhibition and other apoptosis-inducing agents. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells. In overnight assays, combinations of PS-341 and TRAIL were much more effective than either agent alone in promoting apoptosis of a murine myeloid leukemia, C1498, and a murine renal cancer, Renca. For C1498 cells, apoptosis sensitization by PS-341 affected neither the activity of nuclear factor kappaB (NF-kappaB) nor the levels of most antiapoptotic proteins. However, reductions in the antiapoptotic protein c-FLIP in response to PS-341 were observed in both C1498 and Renca cells. Treatment of normal bone marrow mixed with C1498 tumor cells for 18 hours with a combination of PS-341 and TRAIL resulted in a specific depletion of the tumor cells. Upon transfer to irradiated syngeneic recipient mice, mixtures treated with the PS-341 plus TRAIL combination resulted in enhanced long-term tumor-free survival of mice. These data therefore support the targeting of apoptotic pathways in tumor cells, using combinations of agents such as PS-341 and TRAIL that interact synergistically to preferentially promote tumor cell apoptosis. JF - Blood AU - Sayers, Thomas J AU - Brooks, Alan D AU - Koh, Crystal Y AU - Ma, Weihong AU - Seki, Naoko AU - Raziuddin, Arati AU - Blazar, Bruce R AU - Zhang, Xia AU - Elliott, Peter J AU - Murphy, William J AD - Basic Sciences Program, SAIC-Frederick, Center for Cancer Research, National Cancer Institute/NIH, Bldg 560, Rm 31-30, Frederick, MD 21702-1201, USA. sayers@mail.ncifcrf.gov Y1 - 2003/07/01/ PY - 2003 DA - 2003 Jul 01 SP - 303 EP - 310 VL - 102 IS - 1 SN - 0006-4971, 0006-4971 KW - Apoptosis Regulatory Proteins KW - 0 KW - Boronic Acids KW - CASP8 and FADD-Like Apoptosis Regulating Protein KW - Carrier Proteins KW - Cflar protein, mouse KW - Intracellular Signaling Peptides and Proteins KW - Membrane Glycoproteins KW - Protease Inhibitors KW - Pyrazines KW - TNF-Related Apoptosis-Inducing Ligand KW - Tnfsf10 protein, mouse KW - Tumor Necrosis Factor-alpha KW - Bortezomib KW - 69G8BD63PP KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Protease Inhibitors -- pharmacology KW - Disease-Free Survival KW - Bone Marrow Purging KW - Transplantation, Isogeneic KW - Mice KW - Neoplasms, Experimental -- pathology KW - Protease Inhibitors -- therapeutic use KW - Tumor Cells, Cultured KW - Treatment Outcome KW - Neoplasms, Experimental -- drug therapy KW - Drug Synergism KW - Boronic Acids -- pharmacology KW - Pyrazines -- therapeutic use KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Pyrazines -- pharmacology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Carrier Proteins -- drug effects KW - Apoptosis -- drug effects KW - Membrane Glycoproteins -- therapeutic use KW - Carrier Proteins -- analysis KW - Membrane Glycoproteins -- pharmacology KW - Tumor Necrosis Factor-alpha -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Boronic Acids -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73391358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+proteasome+inhibitor+PS-341+sensitizes+neoplastic+cells+to+TRAIL-mediated+apoptosis+by+reducing+levels+of+c-FLIP.&rft.au=Sayers%2C+Thomas+J%3BBrooks%2C+Alan+D%3BKoh%2C+Crystal+Y%3BMa%2C+Weihong%3BSeki%2C+Naoko%3BRaziuddin%2C+Arati%3BBlazar%2C+Bruce+R%3BZhang%2C+Xia%3BElliott%2C+Peter+J%3BMurphy%2C+William+J&rft.aulast=Sayers&rft.aufirst=Thomas&rft.date=2003-07-01&rft.volume=102&rft.issue=1&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-19 N1 - Date created - 2003-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of CYP1A2 as the main isoform for the phase I hydroxylated metabolism of genistein and a prodrug converting enzyme of methylated isoflavones. AN - 73389190; 12814970 AB - This study determined the cytochrome P450 (P450) isoforms responsible for metabolism of isoflavones using human liver microsomes (HLM) and expressed P450s. The primary metabolite of genistein is 3'-OH-genistein, as identified with an authentic chemically synthesized standard. CYP1A2 was predominantly responsible for 3'-OH-genistein formation since its formation was inhibited (>50%, p < 0.05) by a monoclonal antibody specific for CYP1A2, was correlated with CYP1A2 activities of HLM, and was catalyzed by expressed CYP1A2. In addition to CYP1A2, CYP2E1 also catalyzed, although to a lesser extent, its formation. The contribution of these P450s to the formation of 3'-OH-genistein was also confirmed with a panel of expressed enzymes. Methylated isoflavones biochanin A, prunetin, and formononetin (10-100 microM) were rapidly converted by HLM and expressed CYP1A2 to more active genistein and daidzein. The conversion of biochanin A to genistein appears to be mainly mediated by CYP1A2 because of the strong correlation between the conversion rates and CYP1A2 activities in HLM. Thus, CYP1A2 is an effective prodrug-converting enzyme for less active methylated isoflavones. CYP1A2-catalyzed conversion of biochanin A to genistein (Km, 7.80 microM; Vmax, 903 pmol/min/mg of protein; Vmax/Km, 116 microl/min/mg of protein) was much faster than 3'-hydroxylation of genistein (Km, 12.7 microM and Vmax, 109 pmol/min/mg of protein; Vmax/Km, 8.6 microl/min/mg of protein). The interaction studies showed that genistein inhibited formation of acetaminophen from phenacetin with an IC50 value of 16 microM. Additional studies showed that phenacetin and genistein were mutually inhibitory. In conclusion, CYP1A2 and CYP2E1 metabolized genistein and CYP1A2 acted as prodrug-converting enzymes for other less active methylated isoflavones. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Hu, Ming AU - Krausz, Kristopher AU - Chen, Jun AU - Ge, Xia AU - Li, Jianqi AU - Gelboin, Harry L AU - Gonzalez, Frank J AD - LAboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Healh, Bethesda, Maryland, USA. minghu@wsu.edu Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 924 EP - 931 VL - 31 IS - 7 SN - 0090-9556, 0090-9556 KW - 2'-hydroxy-genistein KW - 0 KW - 3'-hydroxy-genistein KW - 4,6-di(methoxymethoxy)-2-hydroxyacetophenone KW - Acetophenones KW - Antibodies, Monoclonal KW - Isoflavones KW - Prodrugs KW - Protein Isoforms KW - Genistein KW - DH2M523P0H KW - Mixed Function Oxygenases KW - EC 1.- KW - Oxidoreductases, O-Demethylating KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Phenacetin KW - ER0CTH01H9 KW - biochanin A KW - U13J6U390T KW - Index Medicus KW - Molecular Structure KW - Drug Resistance -- physiology KW - Drug Interactions KW - Antibodies, Monoclonal -- metabolism KW - Humans KW - Microsomes, Liver -- metabolism KW - Gene Expression KW - Antibodies, Monoclonal -- pharmacology KW - Oxidoreductases, O-Demethylating -- metabolism KW - Hydroxylation KW - Biotransformation KW - Microsomes, Liver -- enzymology KW - Acetophenones -- chemistry KW - Prodrugs -- metabolism KW - Methylation KW - Phenacetin -- metabolism KW - Mixed Function Oxygenases -- metabolism KW - Isoflavones -- administration & dosage KW - Isoflavones -- metabolism KW - Genistein -- metabolism KW - Cytochrome P-450 CYP1A2 -- chemistry KW - Genistein -- analogs & derivatives KW - Cytochrome P-450 CYP1A2 -- pharmacokinetics KW - Genistein -- chemistry KW - Cytochrome P-450 CYP1A2 -- biosynthesis KW - Isoflavones -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73389190?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Identification+of+CYP1A2+as+the+main+isoform+for+the+phase+I+hydroxylated+metabolism+of+genistein+and+a+prodrug+converting+enzyme+of+methylated+isoflavones.&rft.au=Hu%2C+Ming%3BKrausz%2C+Kristopher%3BChen%2C+Jun%3BGe%2C+Xia%3BLi%2C+Jianqi%3BGelboin%2C+Harry+L%3BGonzalez%2C+Frank+J&rft.aulast=Hu&rft.aufirst=Ming&rft.date=2003-07-01&rft.volume=31&rft.issue=7&rft.spage=924&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-10 N1 - Date created - 2003-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel mechanism for irregular firing of a neuron in response to periodic stimulation: irregularity in the absence of noise. AN - 73389169; 12843694 AB - Irregular firing of action potentials (AP's) is a characteristic feature of neurons in the brain. The variability has been attributed to noise from various sources. This study illustrates an alternative mechanism, namely, deterministic irregularity within a model of ionic conductances. Specifically, a model based on modern measurements of the Na+ and K+ current components from the squid giant axon fires irregularly in response to a continuous train of near-threshold current pulses. The interspike interval histogram from these simulations is multi-modal, a result which in other systems has been attributed to stochastic resonance. Moreover, the simulations exhibited short burst of spikes followed by relatively long quiescent periods, a result suggestive of patterned input to the model even though the input consisted of a train of regularly spaced current pulses. The variability of firing is attributable to variations in AP parameters, in particular AP amplitude. The action potential for squid giant axons is not all-or-none. Rather, it is fundamentally a continuous function of stimulus amplitude. That is, the membrane lacks a threshold. Variation in AP amplitude, and to a lesser extent, AP duration, can produce variations in the time to a subsequent AP, which represents a paradigm shift for understanding irregular neuronal firing. The emphasis is not as much on events prior to an AP as it is on the AP's themselves. JF - Journal of computational neuroscience AU - Clay, John R AD - Ion Channel Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. jrclay@ninds.nih.gov PY - 2003 SP - 43 EP - 51 VL - 15 IS - 1 SN - 0929-5313, 0929-5313 KW - Potassium Channels KW - 0 KW - Sodium Channels KW - Index Medicus KW - Animals KW - Patch-Clamp Techniques KW - Electric Capacitance -- adverse effects KW - Stochastic Processes KW - Noise KW - Membrane Potentials KW - Decapodiformes KW - Acoustic Stimulation -- methods KW - Synaptic Transmission KW - Axons -- physiology KW - Potassium Channels -- metabolism KW - Neurons -- metabolism KW - Neurons -- physiology KW - Sodium Channels -- metabolism KW - Action Potentials KW - Periodicity KW - Models, Theoretical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73389169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+computational+neuroscience&rft.atitle=A+novel+mechanism+for+irregular+firing+of+a+neuron+in+response+to+periodic+stimulation%3A+irregularity+in+the+absence+of+noise.&rft.au=Clay%2C+John+R&rft.aulast=Clay&rft.aufirst=John&rft.date=2003-07-01&rft.volume=15&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Journal+of+computational+neuroscience&rft.issn=09295313&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-01 N1 - Date created - 2003-07-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity of acetaminophen, salicylic acid, and caffeine for first-passage rat renal inner medullary collecting duct cells. AN - 73387919; 12663684 AB - Chronic excess ingestion of nonsteroid anti-inflammatory drugs causes renal medullary necrosis. Previously, using an immortalized line of mouse inner medullary collecting ducts cells (mIMCD3), we found that acetaminophen, salicylic acid, and caffeine are toxic, and the effects of acetaminophen and caffeine are strongly additive. Furthermore, toxicity was greater in proliferating than in nonproliferating cells. Important limitations were that mIMCD3 cells do not readily tolerate the high concentrations of salt and urea normally present in renal inner medullas and proliferate much more rapidly than inner medullary cells in vivo. Thus, these cells may not serve as an appropriate model for the in vivo IMCD. The present studies address these limitations by using passage-1 rat inner medullary collecting duct (p1rIMCD) cells, which tolerate high salt and urea and become contact inhibited when confluent. At 640 mOsmol/kg (the lowest normal inner medullary osmolality), the drugs, singly and in combination, reduce the number of proliferating (i.e., subconfluent) p1rIMCD cells more than they do confluent cells. Effects of acetaminophen and caffeine are strongly additive. Addition of as little as 0.1 mM caffeine significantly enhances the toxicity of acetaminophen plus salicylic acid. With confluent cells at 640 mOsmol/kg and very slowly growing cells at 1370 mOsmol/kg, combinations of drugs that include acetaminophen increase proliferation, accompanied by DNA damage and apoptosis. We conclude that these drugs are toxic to renal inner medullary collecting duct cells under the conditions of high osmolality normally present in the inner medulla, that combinations of the drugs are more toxic than are the drugs individually, and that the toxicity includes induction of proliferation of these cells that are otherwise quiescent in the presence of high osmolality. JF - The Journal of pharmacology and experimental therapeutics AU - Cai, Qi AU - Dmitrieva, Natalia I AU - Michea, Luis F AU - Rocha, Gerson AU - Ferguson, Douglas AU - Burg, Maurice B AD - Laboratory of Kidney and Electrolytes Metabolism, National Heart, Lung, and Blood Institute Department of Health and Human Services, National Institutes of Health, Bethesda, MD 20892-1603, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 35 EP - 42 VL - 306 IS - 1 SN - 0022-3565, 0022-3565 KW - Keratolytic Agents KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - Caffeine KW - 3G6A5W338E KW - Salicylic Acid KW - O414PZ4LPZ KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Cell Count KW - Cells, Cultured KW - Cell Division -- drug effects KW - Keratolytic Agents -- pharmacology KW - Mice KW - Salicylic Acid -- pharmacology KW - Kidney Tubules, Collecting -- cytology KW - Kidney Tubules, Collecting -- drug effects KW - Kidney Medulla -- drug effects KW - Caffeine -- pharmacology KW - Kidney Medulla -- cytology KW - Acetaminophen -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73387919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Toxicity+of+acetaminophen%2C+salicylic+acid%2C+and+caffeine+for+first-passage+rat+renal+inner+medullary+collecting+duct+cells.&rft.au=Cai%2C+Qi%3BDmitrieva%2C+Natalia+I%3BMichea%2C+Luis+F%3BRocha%2C+Gerson%3BFerguson%2C+Douglas%3BBurg%2C+Maurice+B&rft.aulast=Cai&rft.aufirst=Qi&rft.date=2003-07-01&rft.volume=306&rft.issue=1&rft.spage=35&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 - 2003-07-24 N1 - Date created - 2003-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene expression patterns as potential molecular biomarkers for malignant transformation in human keratinocytes treated with MNNG, arsenic, or a metal mixture. AN - 73386465; 12773770 AB - In previous studies, treatment with 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) enhanced malignant transformation of immortal human epidermal (RHEK-1) keratinocytes. In contrast, arsenic (As) alone or in a mixture of As, cadmium (Cd), chromium (Cr), and lead (Pb) inhibited this process. Microarray analysis showed unique gene expression patterns in RHEK-1 exposed to MNNG, As, or the metal mixture. From this analysis, we have selected 16 genes potentially involved in the enhancement or inhibition of transformation. These 16 genes, nine (IFN inducible protein 9-27, MAA A32, CCLB protein, integrin beta4, XRCC1, K8, K18, MT3, MAPKK6) of which were altered in a chemical-specific manner and seven (MIC1, bikunin, MTS1, BMP4, RAD23A, DOC2, vimentin) of which were commonly affected by the MNNG and As or mixture treatments, were examined for expression in detail by real-time RT-PCR. Qualitatively, both microarray and real-time RT-PCR analyses gave comparable results for 15 of 16 genes, i.e., genes were consistently induced or suppressed under the different treatment regimens when measured by either technique. Of the seven genes altered in their expression by multiple chemical treatments, five showed patterns consistent with a role in the transformation process, i.e., they were oppositely regulated in MNNG-transformed RHEK-1 cells (designated as OM3) as compared to the nonmalignant As- and mixture-exposed cells. Through time-course studies, we also identified markers whose expression correlates with acquisition of transformation-associated characteristics in OM3. Identification of a battery of genes altered during progressive transformation of RHEK-1 should aid in developing a mechanistic understanding of this process, as well as strengthening the utility of these genes as biomarkers. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Bae, Dong-Soon AU - Handa, Robert J AU - Yang, Raymond S H AU - Campain, Julie A AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 32 EP - 42 VL - 74 IS - 1 SN - 1096-6080, 1096-6080 KW - Arsenates KW - 0 KW - Enzyme Inhibitors KW - Purine Nucleosides KW - Pyrimidinones KW - Pyrroles KW - Sulfhydryl Reagents KW - forodesine KW - 426X066ELK KW - Inosine KW - 5A614L51CT KW - Purine-Nucleoside Phosphorylase KW - EC 2.4.2.1 KW - Dithiothreitol KW - T8ID5YZU6Y KW - Index Medicus KW - Animals KW - Humans KW - Spectrophotometry, Atomic KW - Bile -- metabolism KW - Pyrroles -- pharmacology KW - Chromatography, High Pressure Liquid KW - Rats KW - Oxidation-Reduction KW - Inosine -- pharmacology KW - Biotransformation KW - Pyrimidinones -- pharmacology KW - Dithiothreitol -- pharmacology KW - In Vitro Techniques KW - Rats, Wistar KW - Sulfhydryl Reagents -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Male KW - Purine-Nucleoside Phosphorylase -- metabolism KW - Purine-Nucleoside Phosphorylase -- antagonists & inhibitors KW - Arsenates -- blood KW - Erythrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73386465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Gene+expression+patterns+as+potential+molecular+biomarkers+for+malignant+transformation+in+human+keratinocytes+treated+with+MNNG%2C+arsenic%2C+or+a+metal+mixture.&rft.au=Bae%2C+Dong-Soon%3BHanda%2C+Robert+J%3BYang%2C+Raymond+S+H%3BCampain%2C+Julie+A&rft.aulast=Bae&rft.aufirst=Dong-Soon&rft.date=2003-07-01&rft.volume=74&rft.issue=1&rft.spage=32&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-02 N1 - Date created - 2003-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol expectancies, alcohol consumption, and problem drinking: the moderating role of family history. AN - 73386266; 12788259 AB - The purpose of this investigation was to examine the moderating role of family history (FH) of alcohol use disorders on the association between positive alcohol expectancies and drinking behavior (quantity/frequency of drinking and alcohol-related problems). Lifetime DSM-III-R diagnoses of alcohol abuse/dependence in probands from the Yale Family Study were used to classify FH status of adult relatives, yielding 149 relatives of probands with alcohol abuse/dependence and 110 relatives of controls. Significant main effects were found for FH of alcoholism on problem drinking symptoms and for alcohol expectancies concerning both problem drinking symptoms and quantity/frequency of alcohol use. Regarding moderating effects, there was a significant interaction between alcohol expectancies and FH only for problem drinking symptoms. When familial density of alcoholism was examined as a moderator, significant effects were found for all drinking variables, thus demonstrating that the degree to which alcohol expectancies was associated with the drinking outcomes varied by the extent to which alcohol use disorders clustered in families. The findings are discussed in terms of the interaction of alcohol-related risk factors and the importance of using multiple indicators of familial vulnerability. JF - Addictive behaviors AU - Conway, Kevin P AU - Swendsen, Joel D AU - Merikangas, Kathleen Ries AD - Division of Epidemiology, Services, and Prevention Research, National Institute on Drug Abuse, 6001 Executive Boulevard, Suite 5151 MSC 9589, Bethesda, MD 20892-9589, USA. kconway@nida.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 823 EP - 836 VL - 28 IS - 5 SN - 0306-4603, 0306-4603 KW - Index Medicus KW - Pedigree KW - Risk Factors KW - Humans KW - Cohort Studies KW - Adult KW - Middle Aged KW - Male KW - Female KW - Alcohol Drinking -- psychology KW - Family KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73386266?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addictive+behaviors&rft.atitle=Alcohol+expectancies%2C+alcohol+consumption%2C+and+problem+drinking%3A+the+moderating+role+of+family+history.&rft.au=Conway%2C+Kevin+P%3BSwendsen%2C+Joel+D%3BMerikangas%2C+Kathleen+Ries&rft.aulast=Conway&rft.aufirst=Kevin&rft.date=2003-07-01&rft.volume=28&rft.issue=5&rft.spage=823&rft.isbn=&rft.btitle=&rft.title=Addictive+behaviors&rft.issn=03064603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-05 N1 - Date created - 2003-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-4 synergistically enhances both IL-2- and IL-12-induced IFN-gamma expression in murine NK cells. AN - 73382102; 12637316 AB - Interleukin-4 (IL-4) is thought to influence T and natural killer (NK) cells by down-regulating T helper 1 (Th1)-type cytokines like interferon-gamma (IFN-gamma). While investigating IL-4 regulation of IFN-gamma expression, we found that IL-4 synergized with IL-2 or IL-12 to enhance IFN-gamma production and mRNA expression in spleen-derived, IL-2-cultured NK cells, as well as negatively sorted fresh DX5+/CD3- NK cells albeit at lower levels. The positive effect of IL-4 on IL-2-induced IFN-gamma production was dependent upon signal transducer and activator of transcription 6 (Stat6) because this response was virtually abrogated in Stat6-/- mice. Notably, though, IL-12 plus IL-4 synergy on IFN-gamma expression was intact in Stat6-/- mice. In exploring possible molecular mechanisms to account for the synergistic effects of IL-4 on murine NK cells, we found that IL-2 plus IL-4 stimulation resulted in a modest increase in tyrosine phosphorylation of Stat5, while IL-12 plus IL-4 treatment resulted in a more substantial increase in tyrosine-phosphorylated Stat4. Finally, to identify regions of the IFN-gamma promoter that may be involved, NK cells from human IFN-gamma promoter/luciferase transgenic mice were treated with cytokines. NK cells from proximal (-110 to +64) promoter region mice did not respond to cytokine stimulation; however, the intact -565 to +64 IFN-gamma promoter responded synergistically to IL-2 plus IL-4 and to IL-12 plus IL-4 in NK cells. These data demonstrate a role for IL-4 in enhancing IFN-gamma expression in murine NK cells that is partially dependent on Stat6 in IL-2 costimulation and completely independent of Stat6 in IL-12 costimulations. JF - Blood AU - Bream, Jay H AU - Curiel, Rafael E AU - Yu, Cheng-Rong AU - Egwuagu, Charles E AU - Grusby, Michael J AU - Aune, Thomas M AU - Young, Howard A AD - Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, Building 560, Room 31-23, Frederick, MD 21702-1201, USA. breamj@mail.nih.gov Y1 - 2003/07/01/ PY - 2003 DA - 2003 Jul 01 SP - 207 EP - 214 VL - 102 IS - 1 SN - 0006-4971, 0006-4971 KW - DNA-Binding Proteins KW - 0 KW - Interleukin-2 KW - Interleukins KW - Milk Proteins KW - STAT4 Transcription Factor KW - STAT5 Transcription Factor KW - STAT6 Transcription Factor KW - Stat4 protein, mouse KW - Stat6 protein, mouse KW - Trans-Activators KW - Interleukin-12 KW - 187348-17-0 KW - Interleukin-4 KW - 207137-56-2 KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Interleukin-2 -- pharmacology KW - Promoter Regions, Genetic -- physiology KW - Interleukin-4 -- pharmacology KW - Mice KW - Mice, Knockout KW - Phosphorylation KW - Trans-Activators -- genetics KW - Gene Expression Regulation -- drug effects KW - Interleukin-12 -- pharmacology KW - Trans-Activators -- physiology KW - Drug Synergism KW - DNA-Binding Proteins -- metabolism KW - Interleukins -- pharmacology KW - Interferon-gamma -- genetics KW - Interferon-gamma -- biosynthesis KW - Killer Cells, Natural -- metabolism KW - Killer Cells, Natural -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73382102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=IL-4+synergistically+enhances+both+IL-2-+and+IL-12-induced+IFN-gamma+expression+in+murine+NK+cells.&rft.au=Bream%2C+Jay+H%3BCuriel%2C+Rafael+E%3BYu%2C+Cheng-Rong%3BEgwuagu%2C+Charles+E%3BGrusby%2C+Michael+J%3BAune%2C+Thomas+M%3BYoung%2C+Howard+A&rft.aulast=Bream&rft.aufirst=Jay&rft.date=2003-07-01&rft.volume=102&rft.issue=1&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-19 N1 - Date created - 2003-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Are over-simplified views of addiction neuroscience providing too simplified ethical considerations? AN - 73381464; 12814491 JF - Addiction (Abingdon, England) AU - Uhl, George R AD - Molecular Neurobiology Branch, NIDA-IRP, NIH, Baltimore, MD 21224, USA. guhl@intra.nida.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 872 EP - 873 VL - 98 IS - 7 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Humans KW - Brain Diseases -- rehabilitation KW - Substance-Related Disorders -- etiology KW - Neurosciences -- ethics KW - Human Experimentation -- ethics KW - Substance-Related Disorders -- rehabilitation KW - Ethics, Research KW - Brain Diseases -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73381464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Are+over-simplified+views+of+addiction+neuroscience+providing+too+simplified+ethical+considerations%3F&rft.au=Uhl%2C+George+R&rft.aulast=Uhl&rft.aufirst=George&rft.date=2003-07-01&rft.volume=98&rft.issue=7&rft.spage=872&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 - 2003-09-16 N1 - Date created - 2003-06-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Addiction. 2003 Jul;98(7):867-70 [12814489] Addiction. 2003 Jul;98(7):873-4 [12814492] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic structure and promoter analysis of PKC-delta. AN - 73372802; 12809676 AB - Protein kinase C-delta (PKC-delta) is a ubiquitously expressed kinase involved in a variety of cellular signaling pathways including cell growth, differentiation, apoptosis, tumor promotion, and carcinogenesis. While signaling pathways downstream of PKC-delta are well studied, the regulation of the gene has not been extensively analyzed. A mouse genomic DNA fragment containing the PKC-delta gene was sequenced by the primer-walking method, and the subsequent DNA sequence data were used as a query to clone Caenorhabditis elegans and human genomic homologs from the publicly available genomic databases. The genomic structures of C. elegans, mouse, rat, and human PKC-delta were analyzed, and the result revealed that PKC-delta genes comprise 12, 18, 19, and 18 exons for C. elegans, mouse, rat, and human, respectively. The translation start methionine resides in the second exon in mouse and human and in the third exon in rat. The first intron between the first exon and the exon with the translation start methionine in mammalian genes represents a very large gap, as long as 17 kb in human, indicating a complexity involved in gene splicing. Overall exon-intron genomic structure is highly conserved among mammals, while significantly diverged in C. elegans. Putative transcription factor binding sites on the 1.7-kb promoter region of the mouse gene suggest that PKC-delta might be involved in spermatogenesis, embryogenesis, development, brain generation, immune response, oxidative environment, and oncogenesis. Studies on the promoter and subsequent biological testing on mouse keratinocytes indicate that tumor necrosis factor (TNF)-alpha increases the expression of PKC-delta, and this correlates with the time of NFkappaB nuclear translocation and activation. This TNF-alpha-mediated upregulation of PKC-delta is repressed in keratinocytes that are preinfected with IkappaB superrepressor adenovirus, suggesting that NFkappaB is involved directly in PKC-delta expression. JF - Genomics AU - Suh, Kwang S AU - Tatunchak, Tamara T AU - Crutchley, John M AU - Edwards, Lindsay E AU - Marin, Keith G AU - Yuspa, Stuart H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 57 EP - 67 VL - 82 IS - 1 SN - 0888-7543, 0888-7543 KW - Isoenzymes KW - 0 KW - Tumor Necrosis Factor-alpha KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Animals KW - Genome, Human KW - Exons KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Tumor Necrosis Factor-alpha -- physiology KW - Mice KW - Sequence Analysis, DNA KW - Mice, Inbred BALB C KW - Genome KW - Evolution, Molecular KW - Caenorhabditis elegans -- genetics KW - Rats KW - Regulatory Sequences, Nucleic Acid KW - Animals, Newborn KW - Base Sequence KW - Cells, Cultured KW - Keratinocytes -- enzymology KW - Introns KW - Species Specificity KW - Protein Kinase C -- metabolism KW - Promoter Regions, Genetic KW - Protein Kinase C -- genetics KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - Genes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73372802?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Genomic+structure+and+promoter+analysis+of+PKC-delta.&rft.au=Suh%2C+Kwang+S%3BTatunchak%2C+Tamara+T%3BCrutchley%2C+John+M%3BEdwards%2C+Lindsay+E%3BMarin%2C+Keith+G%3BYuspa%2C+Stuart+H&rft.aulast=Suh&rft.aufirst=Kwang&rft.date=2003-07-01&rft.volume=82&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-23 N1 - Date created - 2003-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection against Adriamycin cytotoxicity and inhibition of DNA topoisomerase II activity by 3,4-dihydroxybenzoic acid. AN - 73365605; 12792789 AB - The mechanism of Adriamycin (ADR) induced cytotoxicity is not completely understood. While a variety of mechanisms have been proposed, the production of free radicals by redox cycling of the semiquinone has been implicated in cytotoxicity, specifically for cardiotoxicity. To determine whether a scavenger of free radicals would modify the cytotoxicity of ADR, the benzoic acid derivative 3,4-dihydroxybenzoic acid (DHB) was investigated for its ability to protect against ADR-induced cytotoxicity and DNA double strand breaks in Chinese hamster V79 cells. V79 cells were treated with ADR, or its non-redox cycling analog iminodaunomycin, in the presence or absence of DHB. DHB provided significant protection (dose-modifying factor greater than 2.5 for ADR, and nearly 2 for iminodaunomycin) and also caused a dose-dependent decrease in DNA double strand breaks as measured by pulsed field gel electrophoresis. Assays of topoisomerase II activity showed that DHB inhibited topoisomerase II in a concentration-dependent manner, but did not inhibit topoisomerase I. Another non-toxic topoisomerase II inhibitor, the radioprotector WR-1065, also protected against ADR-induced cytotoxicity. These data identify DHB as a non-toxic inhibitor of DNA topoisomerase II and suggest that much of the cytotoxicity of ADR in actively growing V79 cells is due to mechanisms other than redox cycling by the semiquinone. JF - International journal of oncology AU - De Graff, William G AU - Myers, L S AU - Mitchell, James B AU - Hahn, Stephen M AD - Radiation Biology Branch, National Cancer Institute/NIH, Building 10, Room B3-B69, 10 Center Drive, Bethesda, MD 20892, USA. degraff@helix.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 159 EP - 163 VL - 23 IS - 1 SN - 1019-6439, 1019-6439 KW - Antibiotics, Antineoplastic KW - 0 KW - Anticarcinogenic Agents KW - Antineoplastic Agents KW - Free Radicals KW - Hydroxybenzoates KW - Topoisomerase II Inhibitors KW - protocatechuic acid KW - 36R5QJ8L4B KW - 5-iminodaunorubicin KW - 72983-78-9 KW - Doxorubicin KW - 80168379AG KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Daunorubicin KW - ZS7284E0ZP KW - Index Medicus KW - Animals KW - DNA Damage KW - Dose-Response Relationship, Drug KW - DNA Topoisomerases, Type II -- metabolism KW - Antibiotics, Antineoplastic -- toxicity KW - Cell Survival KW - Oxidation-Reduction KW - Antibiotics, Antineoplastic -- pharmacology KW - Anticarcinogenic Agents -- pharmacology KW - Electrophoresis, Agar Gel KW - Antineoplastic Agents -- pharmacology KW - Cell Line KW - DNA Topoisomerases, Type I -- metabolism KW - Cricetinae KW - Daunorubicin -- pharmacology KW - Doxorubicin -- pharmacology KW - Hydroxybenzoates -- pharmacology KW - Doxorubicin -- toxicity KW - Daunorubicin -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73365605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+oncology&rft.atitle=Protection+against+Adriamycin+cytotoxicity+and+inhibition+of+DNA+topoisomerase+II+activity+by+3%2C4-dihydroxybenzoic+acid.&rft.au=De+Graff%2C+William+G%3BMyers%2C+L+S%3BMitchell%2C+James+B%3BHahn%2C+Stephen+M&rft.aulast=De+Graff&rft.aufirst=William&rft.date=2003-07-01&rft.volume=23&rft.issue=1&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-18 N1 - Date created - 2003-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA variants of DLC-1, a candidate tumor suppressor gene in human hepatocellular carcinoma. AN - 73364752; 12792785 AB - The DLC-1 gene encoding a regulator of the Rho family of small GTPases is altered in breast, prostate, colon, and liver cancer and has several characteristics of a tumor suppressor gene. DLC-1 overexpression causes inhibition of in vitro growth of liver tumor cells and complete suppression of in vivo tumorigenicity of breast tumor cells. Inactivation and aberrant expression of DLC-1 in human hepatocellular carcinoma (HCC) is frequently associated with hemizygous and homozygous genomic deletion and promoter methylation. Since inactivation of tumor suppressor genes in cancer cells is also commonly associated with point mutation, we evaluated the incidence of mutation of the DLC-1 gene by PCR-SSCP in 17 primary HCC and 18 HCC cell lines. One missense mutation was detected at codon 991 of exon 12 (C-->T transition, Val-->Ile) in an HCC cell line. In addition, two types of polymorphisms were identified: a G-->T at codon 745 of exon 9, a T-->C at 17 bp downstream of exon 2. While the pathogenic relevance of the intronic polymorphism is not known, the low rate of mutation of the DLC-1 gene in HCC implies that genomic deletion and promoter methylation primarily account for the altered expression and tumor suppressive inactivation of the DLC-1 gene. JF - International journal of oncology AU - Park, Sang-Won AU - Durkin, Marian E AU - Thorgeirsson, Snorri S AU - Popescu, Nicholas C AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute/NIH, 37 Convent Drive, Bethesda, MD 20892, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 133 EP - 137 VL - 23 IS - 1 SN - 1019-6439, 1019-6439 KW - Codon KW - 0 KW - DLC1 protein, human KW - DNA, Complementary KW - GTPase-Activating Proteins KW - RNA, Messenger KW - Tumor Suppressor Proteins KW - Index Medicus KW - Homozygote KW - Exons KW - DNA Mutational Analysis KW - Humans KW - Disease Progression KW - Cell Line, Tumor KW - Reverse Transcriptase Polymerase Chain Reaction KW - Polymorphism, Single-Stranded Conformational KW - Gene Expression Regulation, Neoplastic KW - Promoter Regions, Genetic KW - Gene Expression Regulation, Enzymologic KW - RNA, Messenger -- metabolism KW - DNA Methylation KW - DNA, Complementary -- metabolism KW - Point Mutation KW - Introns KW - Mutation KW - Polymorphism, Genetic KW - Genes, Tumor Suppressor KW - Carcinoma, Hepatocellular -- genetics KW - Tumor Suppressor Proteins -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73364752?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+oncology&rft.atitle=DNA+variants+of+DLC-1%2C+a+candidate+tumor+suppressor+gene+in+human+hepatocellular+carcinoma.&rft.au=Park%2C+Sang-Won%3BDurkin%2C+Marian+E%3BThorgeirsson%2C+Snorri+S%3BPopescu%2C+Nicholas+C&rft.aulast=Park&rft.aufirst=Sang-Won&rft.date=2003-07-01&rft.volume=23&rft.issue=1&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=International+journal+of+oncology&rft.issn=10196439&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-18 N1 - Date created - 2003-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct interstitial infusion of NK1-targeted neurotoxin into the spinal cord: a computational model. AN - 73347075; 12793999 AB - Convection-enhanced delivery of substance P (SP) nocitoxins to the spinal cord interstitium is under consideration for the treatment of chronic pain. To characterize treatment protocols, a three-dimensional finite-element model of infusion into the human dorsal column was developed to predict the distribution of SP-diphtheria toxin fusion protein (SP-DT') within normal and target tissue. The model incorporated anisotropic convective and diffusive transport through the interstitial space, hydrolysis by peptidases, and intracellular trafficking. For constant SP-DT' infusion (0.1 microl/min), the distribution of cytotoxicity in NK1 receptor-expressing neurons was predicted to reach an asymptotic limit at 6-8 h in the transverse direction at the level of the infusion cannula tip ( approximately 60% ablation of target neurons in lamina I/II). Computations revealed that SP-DT' treatment was favored by a stable SP analog (half-life approximately 60 min), high infusate concentration (385 nM), and careful catheter placement (adjacent to target lamina I/II). Sensitivity of cytotoxic regions to NK1 receptor density and white matter protease activity was also established. These data suggest that intraparenchymal infusions can be useful for treatment of localized chronic pain. JF - American journal of physiology. Regulatory, integrative and comparative physiology AU - Sarntinoranont, Malisa AU - Iadarola, Michael J AU - Lonser, Russell R AU - Morrison, Paul F AD - Drug Delivery and Kinetics Resource, Div. of Bioengineering and Physical Science, ORS, NIH, Bldg. 13, Rm. 3N17, 13 South Dr., Bethesda, MD 20892-5766, USA. sarntinm@mail.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - R243 EP - R254 VL - 285 IS - 1 SN - 0363-6119, 0363-6119 KW - Neurotoxins KW - 0 KW - Receptors, Neurokinin-1 KW - Substance P KW - 33507-63-0 KW - Index Medicus KW - Pain -- drug therapy KW - Extracellular Space -- metabolism KW - Humans KW - Chronic Disease KW - Receptors, Neurokinin-1 -- physiology KW - Neurotoxins -- pharmacokinetics KW - Spinal Cord -- drug effects KW - Substance P -- pharmacokinetics KW - Spinal Cord -- physiology KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73347075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+physiology.+Regulatory%2C+integrative+and+comparative+physiology&rft.atitle=Direct+interstitial+infusion+of+NK1-targeted+neurotoxin+into+the+spinal+cord%3A+a+computational+model.&rft.au=Sarntinoranont%2C+Malisa%3BIadarola%2C+Michael+J%3BLonser%2C+Russell+R%3BMorrison%2C+Paul+F&rft.aulast=Sarntinoranont&rft.aufirst=Malisa&rft.date=2003-07-01&rft.volume=285&rft.issue=1&rft.spage=R243&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Regulatory%2C+integrative+and+comparative+physiology&rft.issn=03636119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-24 N1 - Date created - 2003-06-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Physiol Regul Integr Comp Physiol. 2003 Jul;285(1):R30-1 [12793991] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cannabinoid CB1 antagonist N-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl) -4-methylpyrazole-3-carboxamide (SR-141716A) differentially alters the reinforcing effects of heroin under continuous reinforcement, fixed ratio, and progressive ratio schedules of drug self-administration in rats. AN - 73345696; 12660305 AB - Activation or blockade of cannabinoid CB1 receptors markedly alters many effects of opioids. In the present study, we investigated whether the cannabinoid antagonist (N-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR-141716A) could alter the reinforcing effects of heroin in rats. A Delta9-tetrahydrocannabinol (THC) drug-discrimination procedure was first used to determine effective CB1 antagonist doses of SR-141716A and optimal pretreatment times for self-administration studies. Subsequently, Sprague-Dawley rats learned to self-administer heroin under three different schedules of intravenous drug injection: a continuous reinforcement schedule [fixed ratio (FR)1], a five-response, fixed ratio schedule (FR5), and a progressive ratio schedule. Then, SR-141716A (1 mg/kg i.p.) was administered 60 min before the start of the session for three consecutive daily sessions. SR-141716A markedly decreased heroin self-administration under the progressive ratio schedule at heroin doses ranging from 12.5 to 100 micro g/kg/injection. In contrast, SR-141716A had no effect on heroin self-administration under the FR1 schedule at heroin doses of 50 or 100 micro g/kg/injection, but produced small decreases in self-administration at lower doses (25 and 12.5 micro g/kg/injection). Consistent with a behavioral economics evaluation, SR-141716A produced a small but significant decrease in self-administration of the higher 50 micro g/kg/injection dose of heroin when the fixed ratio requirement was raised to five (FR5). Thus, blockade of CB1 receptors differentially decreased the reinforcing efficacy of heroin depending on the number of responses required for each injection (price). These findings indicate a facilitatory modulation of opioid reward by endogenous cannabinoid activity and provide support for the use of cannabinoid CB1 antagonists as medications for heroin addiction. JF - The Journal of pharmacology and experimental therapeutics AU - Solinas, M AU - Panlilio, L V AU - Antoniou, K AU - Pappas, L A AU - Goldberg, S R AD - Preclinical Pharmacology Section, Neuroscience Research Branch, National Institute on Drug Abuse, Division of Intramural Research, National Institutes of Health, 5500 Nathan Shock Dr., Baltimore, MD 21224, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 93 EP - 102 VL - 306 IS - 1 SN - 0022-3565, 0022-3565 KW - Analgesics, Opioid KW - 0 KW - Hallucinogens KW - Piperidines KW - Pyrazoles KW - Receptors, Cannabinoid KW - Receptors, Drug KW - Sodium Chloride KW - 451W47IQ8X KW - Heroin KW - 70D95007SX KW - Dronabinol KW - 7J8897W37S KW - rimonabant KW - RML78EN3XE KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Self Administration KW - Analgesics, Opioid -- pharmacology KW - Dronabinol -- pharmacology KW - Hallucinogens -- pharmacology KW - Male KW - Piperidines -- pharmacology KW - Pyrazoles -- pharmacology KW - Heroin -- pharmacology KW - Reinforcement Schedule KW - Receptors, Drug -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73345696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Interpersonal+Violence&rft.atitle=Cyberbullying%3A+The+discriminant+factors+among+cyberbullies%2C+cybervictims%2C+and+cyberbully-victims+in+a+Czech+adolescent+sample&rft.au=Bayraktar%2C+Fatih%3BMachackova%2C+Hana%3BDedkova%2C+Lenka%3BCerna%2C+Alena%3B%C5%A0ev%C4%8D%C3%ADkov%C3%A1%2C+Anna&rft.aulast=Bayraktar&rft.aufirst=Fatih&rft.date=2015-11-01&rft.volume=30&rft.issue=18&rft.spage=3192&rft.isbn=&rft.btitle=&rft.title=Journal+of+Interpersonal+Violence&rft.issn=08862605&rft_id=info:doi/10.1177%2F0886260514555006 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-24 N1 - Date created - 2003-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Patterns of aneuploidy in stage IV clear cell renal cell carcinoma revealed by comparative genomic hybridization and spectral karyotyping. AN - 73312653; 12759923 AB - We report the use of spectral karyotyping (SKY) and comparative genomic hybridization (CGH) to describe the numerous genomic imbalances characteristic of stage IV clear cell renal cell carcinoma (CCRCC). SKY and CGH were performed on 10 cell lines established from nephrectomy specimens, and CGH on uncultured material from five of the primary renal tumors. The mutational status of VHL (3p25) and MET (7q31), genes implicated in renal carcinogenesis, were determined for each case. Each case showed marked aneuploidy, with an average number of copy alterations of 14.6 (+/-2.7) in the primary tumors and 19.3 (+/-4.6) in the cell lines. Both whole-chromosome and chromosome-segment imbalances were noted by CGH: consistent losses or gains included +5q23-->ter (100%), -3p14-->ter (80%), and +7 (70%). All VHL mutations and 83% of the genomic imbalances found in the primary tumors were also found in the cell lines derived from them. SKY showed many complex structural rearrangements that were undetected by conventional banding analysis in these solid tumors. All cases with VHL inactivation had 3p loss and 5q gain related primarily to unbalanced translocations between 3p and 5q. In contrast, gains of chromosome 7 resulted primarily from whole-chromosome gains and were not associated with mutations of MET. SKY and CGH demonstrated that genomic imbalances in advanced RCC were the result of either segregation errors [i.e., whole chromosomal gains and losses (7.8/case)] or chromosomal rearrangements (10.7/case), of which the majority were unbalanced translocations. Copyright 2003 Wiley-Liss, Inc. JF - Genes, chromosomes & cancer AU - Pavlovich, Christian P AU - Padilla-Nash, Hesed AU - Wangsa, Danny AU - Nickerson, Michael L AU - Matrosova, Vera AU - Linehan, W Marston AU - Ried, Thomas AU - Phillips, John L AD - Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 252 EP - 260 VL - 37 IS - 3 SN - 1045-2257, 1045-2257 KW - DNA, Neoplasm KW - 0 KW - Tumor Suppressor Proteins KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Ligases KW - EC 6.- KW - VHL protein, human KW - EC 6.3.2.- KW - Index Medicus KW - Karyotyping KW - Ligases -- genetics KW - Chromosome Deletion KW - Neoplasm Staging KW - Genes, Tumor Suppressor KW - Humans KW - Nucleic Acid Hybridization -- methods KW - Chromosome Painting KW - Proto-Oncogene Proteins c-met -- genetics KW - Tumor Cells, Cultured KW - Gene Amplification -- genetics KW - DNA, Neoplasm -- genetics KW - Female KW - Male KW - Kidney Neoplasms -- genetics KW - Adenocarcinoma, Clear Cell -- genetics KW - Aneuploidy KW - Carcinoma, Renal Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73312653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Patterns+of+aneuploidy+in+stage+IV+clear+cell+renal+cell+carcinoma+revealed+by+comparative+genomic+hybridization+and+spectral+karyotyping.&rft.au=Pavlovich%2C+Christian+P%3BPadilla-Nash%2C+Hesed%3BWangsa%2C+Danny%3BNickerson%2C+Michael+L%3BMatrosova%2C+Vera%3BLinehan%2C+W+Marston%3BRied%2C+Thomas%3BPhillips%2C+John+L&rft.aulast=Pavlovich&rft.aufirst=Christian&rft.date=2003-07-01&rft.volume=37&rft.issue=3&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=10452257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-28 N1 - Date created - 2003-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insertion of MLL sequences into chromosome band 5q31 results in an MLL-AF5Q31 fusion and is a rare but recurrent abnormality associated with infant leukemia. AN - 73292590; 12759932 AB - MLL gene rearrangements leading to production of MLL fusion proteins are commonly detected in infant leukemia patients; the most common MLL fusion associated with infant leukemia is the MLL-AF4 fusion. A single case of chromosomal rearrangement leading to production of an MLL fusion with AF5Q31, a gene structurally similar to AF4, has been detected recently in the malignant cells of an infant leukemia patient. We have identified a second case of MLL-AF5Q31 fusion, arising from an insertion of MLL sequences into chromosome 5, also in an infant leukemia patient. Because MLL and AF5Q31 are transcribed in opposite orientations, a simple balanced chromosomal translocation cannot produce a fusion protein, and complex chromosomal rearrangements such as insertions and inversions are required to produce an MLL-AF5Q31 fusion protein. This report demonstrates that chromosomal insertion of MLL sequences is a rare but recurrent abnormality associated with infant leukemia. Copyright 2003 Wiley-Liss, Inc. JF - Genes, chromosomes & cancer AU - Deveney, Ramona AU - Chervinsky, David S AU - Jani-Sait, Sheila N AU - Grossi, Mauro AU - Aplan, Peter D AD - Genetics Branch, Center for Cancer Research, National Cancer Institute, Gaithersburg, Maryland 20892, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 326 EP - 331 VL - 37 IS - 3 SN - 1045-2257, 1045-2257 KW - DNA-Binding Proteins KW - 0 KW - MLL protein, human KW - Nuclear Proteins KW - Oncogene Proteins, Fusion KW - Transcription Factors KW - Transcriptional Elongation Factors KW - Myeloid-Lymphoid Leukemia Protein KW - 149025-06-9 KW - AFF1 protein, human KW - 150826-18-9 KW - Histone-Lysine N-Methyltransferase KW - EC 2.1.1.43 KW - Index Medicus KW - Infant KW - Fatal Outcome KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Male KW - Leukemia, B-Cell -- genetics KW - Nuclear Proteins -- genetics KW - Oncogene Proteins, Fusion -- genetics KW - DNA-Binding Proteins -- genetics KW - Chromosomes, Human, Pair 5 -- genetics KW - Chromosome Aberrations KW - Proto-Oncogenes KW - Leukemia, B-Cell -- drug therapy KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- drug therapy KW - Mutagenesis, Insertional -- genetics KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73292590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Insertion+of+MLL+sequences+into+chromosome+band+5q31+results+in+an+MLL-AF5Q31+fusion+and+is+a+rare+but+recurrent+abnormality+associated+with+infant+leukemia.&rft.au=Deveney%2C+Ramona%3BChervinsky%2C+David+S%3BJani-Sait%2C+Sheila+N%3BGrossi%2C+Mauro%3BAplan%2C+Peter+D&rft.aulast=Deveney&rft.aufirst=Ramona&rft.date=2003-07-01&rft.volume=37&rft.issue=3&rft.spage=326&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=10452257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-28 N1 - Date created - 2003-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Soluble ICAM-1, MCP-1, and MIP-2 protein secretion by rat pleural mesothelial cells following exposure to amosite asbestos. AN - 73270974; 12746042 AB - Pleural inflammation is a sequela of exposure to toxic mineral fibers such as amosite asbestos. This inflammatory response involves the influx of leukocytes from the vasculature into the pleural space. Adhesion molecules such as intercellular adhesion molecule-1 (ICAM)-1 and chemokines such as monocyte chemoattractant protein-1 (MCP)-1 and macrophage inhibitory protein-2 (MIP)-2 are known to be important in pulmonary inflammation following inhalation of particulate matter. However, little is known about their role in pleural inflammation secondary to amosite asbestos exposure. Because the pleural mesothelial cell is believed to be a key target cell of asbestos exposure, the purpose of this study was to determine if ICAM-1, MCP-1, and MIP-2 proteins were secreted by these mesothelial cells following in vitro and in vivo exposure to amosite asbestos. Increased levels of ICAM-1 and MCP-1 protein were measured following 24 or 48 hours exposure of cultured rat pleural mesothelial cells to amosite fibers (1.5 to 5.0 micro g/cm(2)). Increased levels of ICAM-1, MCP-1, and MIP-2 protein were found in pleural lavage fluid from Fischer-344 rats exposed to amosite asbestos for 4 and 12 weeks and after a 12-week recovery period (following the 12-week exposure period). These findings suggest that the secretion of ICAM-1, MCP-1, and MIP-2 by rat pleural mesothelial cells may contribute to amosite-induced pleural inflammation. JF - Experimental lung research AU - Hill, Georgette D AU - Mangum, James B AU - Moss, Owen R AU - Everitt, Jeffrey I AD - Department of Respiratory Toxicology, CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709, USA. hill9@niehs.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 277 EP - 290 VL - 29 IS - 5 SN - 0190-2148, 0190-2148 KW - Chemokine CCL2 KW - 0 KW - Chemokine CXCL2 KW - Chemokines, CXC KW - Culture Media, Conditioned KW - Cxcl2 protein, rat KW - Intercellular Signaling Peptides and Proteins KW - Monokines KW - Asbestos, Crocidolite KW - 12001-28-4 KW - Asbestos, Amosite KW - 12172-73-5 KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Animals KW - Pleural Effusion -- pathology KW - Dose-Response Relationship, Drug KW - Asbestos, Crocidolite -- administration & dosage KW - Pleural Effusion -- metabolism KW - Culture Media, Conditioned -- metabolism KW - Epithelium -- drug effects KW - Rats KW - Rats, Inbred F344 KW - Culture Media, Conditioned -- chemistry KW - Epithelium -- metabolism KW - Administration, Inhalation KW - Epithelium -- pathology KW - Asbestos, Crocidolite -- toxicity KW - Male KW - Pleurisy -- pathology KW - Asbestos, Amosite -- administration & dosage KW - Pleurisy -- metabolism KW - Pleurisy -- chemically induced KW - Asbestos, Amosite -- toxicity KW - Pleura -- drug effects KW - Pleura -- pathology KW - Pleura -- metabolism KW - Monokines -- metabolism KW - Chemokine CCL2 -- metabolism KW - Intercellular Adhesion Molecule-1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73270974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lung+research&rft.atitle=Soluble+ICAM-1%2C+MCP-1%2C+and+MIP-2+protein+secretion+by+rat+pleural+mesothelial+cells+following+exposure+to+amosite+asbestos.&rft.au=Hill%2C+Georgette+D%3BMangum%2C+James+B%3BMoss%2C+Owen+R%3BEveritt%2C+Jeffrey+I&rft.aulast=Hill&rft.aufirst=Georgette&rft.date=2003-07-01&rft.volume=29&rft.issue=5&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Experimental+lung+research&rft.issn=01902148&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-29 N1 - Date created - 2003-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytogenetic, spectral karyotyping, fluorescence in situ hybridization, and comparative genomic hybridization characterization of two new secondary leukemia cell lines with 5q deletions, and MYC and MLL amplification. AN - 73265973; 12759925 AB - Cytogenetic studies of patients with therapy-induced acute myeloid leukemia (t-AML) have demonstrated whole chromosome loss or q-arm deletion of chromosomes 5 and/or 7 in a majority of cases. We have established two cell lines, SAML-1 and SAML-2, from two patients who developed t-AML after radiation and chemotherapy for Hodgkin disease. In both cases, the leukemia cells contained 5q deletions. SAML-1 has 58 chromosomes and numerous abnormalities, including der(1)(1qter-->1p22::5q31-->5qter), der(5)(5pter-->5q22::1p22-->1pter), +8, der(13)i(13)(q10)del(13)(q11q14.1), and t(10;11). Fluorescence in situ hybridization (FISH) with unique sequence probes for the 5q31 region showed loss of IL4, IL5, IRF1, and IL3, and translocation of IL9, DS5S89, EGR1, and CSFIR to 1p. SAML-2 has 45 chromosomes, del(5)(q11.2q31) with a t(12;13)ins(12;5), leading to the proximity of IRF1 and RB1, and complex translocations of chromosomes 8 and 11, resulting in amplification of MYC and MLL. Comparative genomic hybridization and spectral karyotyping were consistent with the G-banding karyotype and FISH analyses. Because a potential tumor suppressor(s) in the 5q31 region has yet to be identified, these cell lines should prove useful in the study of the mechanisms leading to the development of t-AML. Copyright 2003 Wiley-Liss, Inc. JF - Genes, chromosomes & cancer AU - Knutsen, Turid AU - Pack, Svetlana AU - Petropavlovskaja, Maria AU - Padilla-Nash, Hesed AU - Knight, Clement AU - Mickley, Lyn A AU - Ried, Thomas AU - Elwood, Patrick C AU - Roberts, Susan J AD - Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. knutsent@mail.nih.gov Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 270 EP - 281 VL - 37 IS - 3 SN - 1045-2257, 1045-2257 KW - Index Medicus KW - Phenotype KW - Acute Disease KW - Tumor Cells, Cultured KW - Karyotyping -- methods KW - Chromosome Banding KW - Nucleic Acid Hybridization -- methods KW - Humans KW - Adult KW - Middle Aged KW - Male KW - Chromosome Painting KW - Hodgkin Disease -- radiotherapy KW - Cytogenetic Analysis KW - Leukemia, Radiation-Induced -- genetics KW - Hodgkin Disease -- drug therapy KW - Leukemia, Myeloid -- genetics KW - In Situ Hybridization, Fluorescence KW - Leukemia, Myeloid -- complications KW - Hodgkin Disease -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73265973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Cytogenetic%2C+spectral+karyotyping%2C+fluorescence+in+situ+hybridization%2C+and+comparative+genomic+hybridization+characterization+of+two+new+secondary+leukemia+cell+lines+with+5q+deletions%2C+and+MYC+and+MLL+amplification.&rft.au=Knutsen%2C+Turid%3BPack%2C+Svetlana%3BPetropavlovskaja%2C+Maria%3BPadilla-Nash%2C+Hesed%3BKnight%2C+Clement%3BMickley%2C+Lyn+A%3BRied%2C+Thomas%3BElwood%2C+Patrick+C%3BRoberts%2C+Susan+J&rft.aulast=Knutsen&rft.aufirst=Turid&rft.date=2003-07-01&rft.volume=37&rft.issue=3&rft.spage=270&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=10452257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-28 N1 - Date created - 2003-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Genes Chromosomes Cancer. 2003 Jul;37(3):332 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genome manipulation by homologous recombination in Drosophila. AN - 71582550; 15239936 AB - By utilising a cell's recombinational machinery, researchers in many different model organisms have been able to perform gene targeting experiments in which specific sequence alterations are introduced into virtually any endogenous gene. Not only can functional knock-outs be generated by gene targeting, interesting alleles with mutations encoding specific amino acid replacements can also be made. A practical gene targeting method has only recently become available for Drosophila. This article reviews the Drosophila gene targeting method, with emphases placed on different approaches that are being used to generate different mutations. JF - Briefings in functional genomics & proteomics AU - Bi, Xiaolin AU - Rong, Yikang S AD - Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20895, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 142 EP - 146 VL - 2 IS - 2 SN - 1473-9550, 1473-9550 KW - Index Medicus KW - Animals KW - Alleles KW - Transgenes KW - Forecasting KW - Mutation KW - Mutagenesis KW - Drosophila melanogaster -- genetics KW - Recombination, Genetic KW - Gene Targeting KW - Genes, Insect UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71582550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Briefings+in+functional+genomics+%26+proteomics&rft.atitle=Genome+manipulation+by+homologous+recombination+in+Drosophila.&rft.au=Bi%2C+Xiaolin%3BRong%2C+Yikang+S&rft.aulast=Bi&rft.aufirst=Xiaolin&rft.date=2003-07-01&rft.volume=2&rft.issue=2&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Briefings+in+functional+genomics+%26+proteomics&rft.issn=14739550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-08-03 N1 - Date created - 2004-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interrogating mouse mammary cancer models: insights from gene expression profiling. AN - 71534577; 14973376 AB - Numerous mouse models for mammary cancer have been developed and characterized based upon their biological, molecular, and histopathological features. In an effort to dissect the molecular anatomy of such models and compare their gene expression profiles to those of human breast cancer, six models representing various oncogenic pathways have been investigated using cDNA microarray technology. Results of these analyses are presented and discussed in the context of technological challenges presented by analyzing data on such a large scale. Further expression profiling coupled with emerging proteomic technologies will more completely define and distinguish mouse models of mammary cancer from each other and provide a comprehensive basis for comparing such models with the human disease they are intended to represent. JF - Journal of mammary gland biology and neoplasia AU - Fargiano, Antonio A AU - Desai, Kartiki V AU - Green, Jeffrey E AD - Transgenic Oncogenesis Group, Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 321 EP - 334 VL - 8 IS - 3 SN - 1083-3021, 1083-3021 KW - Index Medicus KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Disease Progression KW - Mice KW - Gene Expression Regulation, Neoplastic KW - Gene Expression Profiling KW - Mammary Neoplasms, Animal -- genetics KW - Disease Models, Animal KW - Mammary Neoplasms, Animal -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71534577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+mammary+gland+biology+and+neoplasia&rft.atitle=Interrogating+mouse+mammary+cancer+models%3A+insights+from+gene+expression+profiling.&rft.au=Fargiano%2C+Antonio+A%3BDesai%2C+Kartiki+V%3BGreen%2C+Jeffrey+E&rft.aulast=Fargiano&rft.aufirst=Antonio&rft.date=2003-07-01&rft.volume=8&rft.issue=3&rft.spage=321&rft.isbn=&rft.btitle=&rft.title=Journal+of+mammary+gland+biology+and+neoplasia&rft.issn=10833021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-09-17 N1 - Date created - 2004-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and evaluation of substituted naphthalimide nitrogen mustards as rationally designed anticancer compounds. AN - 71507994; 14714857 AB - Bromonapmustine 4a and chloronapmustine 4b, two new nitrogen mustards of substituted naphthalimides, have been synthesized as mixed-function anticancer compounds from 4-bromo- and 4-chloro-N-(2-hydroxyethyl)-naphthalimide respectively following a three-step process. Their chemical alkylating activity exceeded that of nor-HN2. Their antitumour efficacy were assessed in vivo in two murine ascites tumours, namely Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S-180) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. Two standard clinical drugs, namely endoxan (cyclophosphamide) and 5-fluorouracil (5-FU) were used as positive controls for comparison. Both of them have displayed substantial and reproducible antitumoural activity in these tumours comparable with 5-FU. These compounds inhibit the synthesis of DNA and RNA in S-180 tumour cells. These were further screened in vitro in 3 different human tumour cell lines but no significant activity was observed in those lines. JF - Acta poloniae pharmaceutica AU - Pain, A AU - Samanta, S AU - Dutta, S AU - Saxena, A K AU - Shanmugavel, M AU - Kampasi, H AU - Quazi, G N AU - Sanyal, U AD - Department of Anticancer Drug Development, Chittaranjan National Cancer Institute, Calcutta-700026, India. PY - 2003 SP - 285 EP - 291 VL - 60 IS - 4 SN - 0001-6837, 0001-6837 KW - Antineoplastic Agents KW - 0 KW - Antineoplastic Agents, Alkylating KW - DNA, Neoplasm KW - Imides KW - Nitrogen Mustard Compounds KW - RNA, Neoplasm KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Spectroscopy, Fourier Transform Infrared KW - Drug Screening Assays, Antitumor KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Humans KW - Spectrophotometry, Ultraviolet KW - Cell Line, Tumor KW - Drug Design KW - Chromatography, High Pressure Liquid KW - Spectrophotometry, Infrared KW - Antineoplastic Agents, Alkylating -- chemical synthesis KW - Chromatography, Thin Layer KW - DNA, Neoplasm -- biosynthesis KW - Nitrogen Mustard Compounds -- chemical synthesis KW - Antineoplastic Agents -- chemical synthesis KW - Imides -- pharmacology KW - Imides -- chemical synthesis KW - Antineoplastic Agents -- pharmacology KW - Nitrogen Mustard Compounds -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71507994?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+poloniae+pharmaceutica&rft.atitle=Synthesis+and+evaluation+of+substituted+naphthalimide+nitrogen+mustards+as+rationally+designed+anticancer+compounds.&rft.au=Pain%2C+A%3BSamanta%2C+S%3BDutta%2C+S%3BSaxena%2C+A+K%3BShanmugavel%2C+M%3BKampasi%2C+H%3BQuazi%2C+G+N%3BSanyal%2C+U&rft.aulast=Pain&rft.aufirst=A&rft.date=2003-07-01&rft.volume=60&rft.issue=4&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Acta+poloniae+pharmaceutica&rft.issn=00016837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-13 N1 - Date created - 2004-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Molecular epidemiology for the study of the environment-genome interaction]. TT - L'epidemiologia molecolare per lo studio dell'interazione ambiente-genoma. AN - 71312939; 14582283 AB - The study of the gene-environment interaction considered initially genes involved in the biotransformation of carcinogenic agents. Genetic polymorphisms are useful markers of individual susceptibility, provided that their association with the exposure and the outcome of interest are clearly understood. The availability of biochemical and molecular markers in epidemiology research has been greeted as a major step forward from the traditional "black box" epidemiology, and certainly represents a real advancement in knowledge. Yet, the advancement in research made possible by the adoption of molecular biomarkers in epidemiological studies still needs to be evaluated as a relevant and effective tool for a more adequate prevention of the adverse effects caused by environmental agents. JF - Giornale italiano di medicina del lavoro ed ergonomia AU - Baccarelli, A AU - Bertazzi, P A AU - Landi, M T AD - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, DHHS, Bethesda, USA. PY - 2003 SP - 424 EP - 425 VL - 25 IS - 3 SN - 1592-7830, 1592-7830 KW - Index Medicus KW - Humans KW - Environment KW - Genome, Human KW - Molecular Epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71312939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Giornale+italiano+di+medicina+del+lavoro+ed+ergonomia&rft.atitle=%5BMolecular+epidemiology+for+the+study+of+the+environment-genome+interaction%5D.&rft.au=Baccarelli%2C+A%3BBertazzi%2C+P+A%3BLandi%2C+M+T&rft.aulast=Baccarelli&rft.aufirst=A&rft.date=2003-07-01&rft.volume=25&rft.issue=3&rft.spage=424&rft.isbn=&rft.btitle=&rft.title=Giornale+italiano+di+medicina+del+lavoro+ed+ergonomia&rft.issn=15927830&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-23 N1 - Date created - 2003-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Does amount of time spent in child care predict socioemotional adjustment during the transition to kindergarten? AN - 57039220; 234657 AB - To examine relations between time in nonmaternal care through the first 4.5 years of life and children's socioemotional adjustment, data onsocial competence and problem behavior were examined when children participating in the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care were 4.5 years of age and whenin kindergarten. The more time children spent in any of a variety of nonmaternal care arrangements across the first. 4.5 years of life, themore externalizing problems and conflict with adults they manifested at 54 months of age and in kindergarten, as reported by mothers, caregivers, and teachers. These effects remained, for the most part, even when quality, type, and instability of child care were controlled, and when maternal sensitivity and other family background factors were taken into account. The magnitude of quantity of care effects were modestand smaller than those of maternal sensitivity and indicators of family socioeconomic status, though typically greater than those of other features of child care, maternal depression, and infant temperament. There was no apparent threshold for quantity effects. More time in carenot only predicted problem behavior measured on a continuous scale ina dose-response pattern but also predicted at-risk (though not clinical) levels of problem behavior, as well as assertiveness, disobedience, and aggression. (Original abstract) JF - Child Development AU - National Institute of Child Health and Human Development Early Child Care Research Network AD - National Institute of Child Health and Human Development Early Child Care Research Network Y1 - 2003/07// PY - 2003 DA - July 2003 SP - 976 EP - 1005 VL - 74 IS - 4 SN - 0009-3920, 0009-3920 KW - USA KW - Predictors KW - Kindergartens KW - Preschool children KW - Transition KW - Socioemotional aspects KW - Behavioural problems KW - Child care KW - Adjustment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57039220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Does+amount+of+time+spent+in+child+care+predict+socioemotional+adjustment+during+the+transition+to+kindergarten%3F&rft.au=National+Institute+of+Child+Health+and+Human+Development+Early+Child+Care+Research+Network&rft.aulast=National+Institute+of+Child+Health+and+Human+Development+Early+Child+Care+Research+Network&rft.aufirst=&rft.date=2003-07-01&rft.volume=74&rft.issue=4&rft.spage=976&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2003-12-01 N1 - Document feature - refs. tbls. N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Preschool children; Kindergartens; Transition; Adjustment; Socioemotional aspects; Behavioural problems; Predictors; Child care; USA ER - TY - JOUR T1 - Comparison of Diagnostic Accuracy of Biomarkers With Pooled Assessments AN - 21128560; 11157520 AB - New biomarkers are frequently being developed in laboratory settings for the early diagnosis of diseases. However, the assay can be so expensive to assess in some cases that the evaluation of a large number of assays becomes unfeasible. Under this setting pooling biospecimens becomes an appealing alternative. In this paper, we present the methodology to allow for general pooling strategies and different data structures, which include balanced and unbalanced pooling cases. An estimate of the area under the ROC curve of a single biomarker with its asymptotic mean and variance is provided. Furthermore, we develop a test statistic for comparing the areas under the ROC curves of two biomarkers. The methods are illustrated with data from a study evaluating biomarkers for coronary heart disease. JF - Biometrical Journal AU - Liu, Aiyi AU - Schisterman, Enrique F AD - Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development (NICHD), Department of Health and Human Services, 6100 Executive Blvd., Bethesda, MD 20852, schistee@mail.nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 631 EP - 644 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 45 IS - 5 SN - 0323-3847, 0323-3847 KW - Biotechnology and Bioengineering Abstracts KW - Statistics KW - Data processing KW - Biometrics KW - biomarkers KW - Coronary heart disease KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21128560?accountid=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=Biometrical+Journal&rft.atitle=Comparison+of+Diagnostic+Accuracy+of+Biomarkers+With+Pooled+Assessments&rft.au=Liu%2C+Aiyi%3BSchisterman%2C+Enrique+F&rft.aulast=Liu&rft.aufirst=Aiyi&rft.date=2003-07-01&rft.volume=45&rft.issue=5&rft.spage=631&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200390038 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - biomarkers; Data processing; Biometrics; Coronary heart disease; Statistics DO - http://dx.doi.org/10.1002/bimj.200390038 ER - TY - JOUR T1 - Estimation of Sample Size for Reference Interval Studies AN - 21075283; 11132322 AB - The currently used criterion for sample size calculation in a reference interval study is not well stated and leads to imprecise control of the ratio in question. We propose a generalization of the criterion used to determine sufficient sample size in reference interval studies. The generalization allows better estimation of the required sample size when the reference interval estimation will be using a power transformation or is nonparametric. Bootstrap methods are presented to estimate sample sizes required by the generalized criterion. Simulation of several distributions both symmetric and positively skewed is presented to compare the sample size estimators. The new method is illustrated on a data set of plasma glucose values from a 50-g oral glucose tolerance test. It is seen that the sample sizes calculated from the generalized criterion leads to more reliable control of the desired ratio. JF - Biometrical Journal AU - Troendle, James F AU - Yu, Kai F AD - Biometry and Mathematical Statistics Branch, National Institute of Child Health and Human Development, National Institutes of Health, DHHS, Bld. 6100, Room 7B05, Bethesda, MD 20892, USA, jt3t@nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 561 EP - 572 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 45 IS - 5 SN - 0323-3847, 0323-3847 KW - Biotechnology and Bioengineering Abstracts KW - Transformation KW - Data processing KW - Glucose tolerance KW - W 30925:Genetic Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21075283?accountid=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=Biometrical+Journal&rft.atitle=Estimation+of+Sample+Size+for+Reference+Interval+Studies&rft.au=Troendle%2C+James+F%3BYu%2C+Kai+F&rft.aulast=Troendle&rft.aufirst=James&rft.date=2003-07-01&rft.volume=45&rft.issue=5&rft.spage=561&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200390033 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Data processing; Glucose tolerance; Transformation DO - http://dx.doi.org/10.1002/bimj.200390033 ER - TY - JOUR T1 - Gene Duplication with Displacement and Rearrangement: Origin of the Bacterial Replication Protein PriB from the Single-Stranded DNA-Binding Protein Ssb AN - 20150651; 6473535 AB - PriB is a proteobacterial protein that is involved in the pre-primosomal step of DNA replication and, unexpectedly, is encoded with a ribosomal protein operon. Detailed sequence comparisons and analysis of operon organization show that PriB evolved from the single-stranded DNA-binding (Ssb) via gene duplication with subsequent rapid sequence diversification. Duplication of the ssb gene was accompanied by a genome rearrangement which resulted in one of the paralogs retaining the original position, whereas the other was relocated. The functional specialization of the resulting paralogs apparently proceeded in an unexpected fashion: the original Ssb function remained with the relocated paralog, whereas the one within the ribosomal protein operon acquired a new, specialized function in replication. JF - Journal of Molecular Microbiology and Biotechnology AU - Ponomarev, V A AU - Makarova, K S AU - Aravind, L AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894 (USA), koonin@ncbi.nlm.nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 225 EP - 229 VL - 5 IS - 4 SN - 1464-1801, 1464-1801 KW - Genetics Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Genomes KW - Bacteria KW - DNA biosynthesis KW - Replication KW - Ribosomal proteins KW - gene rearrangement KW - ssb gene KW - single-stranded DNA-binding protein KW - Specialization KW - Operons KW - gene duplication KW - A 01490:Miscellaneous KW - N 14820:DNA Metabolism & Structure KW - G 07770:Bacteria KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20150651?accountid=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=Gene+Duplication+with+Displacement+and+Rearrangement%3A+Origin+of+the+Bacterial+Replication+Protein+PriB+from+the+Single-Stranded+DNA-Binding+Protein+Ssb&rft.au=Ponomarev%2C+V+A%3BMakarova%2C+K+S%3BAravind%2C+L%3BKoonin%2C+E+V&rft.aulast=Ponomarev&rft.aufirst=V&rft.date=2003-07-01&rft.volume=5&rft.issue=4&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.issn=14641801&rft_id=info:doi/10.1159%2F000071074 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Genomes; DNA biosynthesis; Ribosomal proteins; Replication; single-stranded DNA-binding protein; ssb gene; gene rearrangement; Specialization; Operons; gene duplication; Bacteria DO - http://dx.doi.org/10.1159/000071074 ER - TY - JOUR T1 - Sorption of Paraquat on Clay Components in Taiwan's Oxisol AN - 19426614; 5788754 AB - The sorption of herbicides in soils is mainly influenced by clay components. The objectives of this study were to evaluate the contribution of clay components on paraquat sorption. The surface soils (0-20 cm) of a Laopi pedon (Fine, mixed, Hyperthermic Typic Hapludox) were separated clays into whole (<2.0 mu m), coarse (0.2-2.0 mu m), and fine (<0.2 mu m) fractions with the treatments of removals of organic matter (OM) and free Fe (Fe sub(d)) oxides. Results indicated that sorption isotherm of paraquat was fitted by the nonlinear Freundlich equation with R super(2) values ranged in 0.79-0.96, respectively. The shape of paraquat adsorption isotherm on the fine fraction was H-type, but their shapes on the whole and coarse fractions were L-types. The fine clay fractions gave higher contribution on paraquat sorption than the coarse clay fractions identified by their K sub(f) values. Organic matter associated with fine clay fraction had high CEC contributing to relatively high affinity for paraquat. The DCB treatment created high-affinity sites for paraquat on the fine clay, but had little effect on paraquat sorption for the coarse clay. Chemisorption is the major mechanism for retention of paraquat on clay components, not ion exchange. However, the silicate clay had the highest affinity for paraquat and free Fe compound had the lowest. JF - Journal of Environmental Science and Health, Part B: Pesticides, Food Contaminants and Agricultural Wastes AU - Hseu, Zeng-Yei AU - Jien, Shih-Hao AU - Cheng, Shuang-Fu AD - Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, 1 Sheuh-Fu Road, Nei-Pu, Pingtung 91201, Taiwan, ROC, zyhseu@mail.npust.edu.tw Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 441 EP - 449 VL - B38 IS - 4 SN - 0360-1234, 0360-1234 KW - paraquat KW - Pollution Abstracts KW - Soil KW - Clay KW - Organic matter KW - Adsorption KW - Herbicides KW - P 5000:LAND POLLUTION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19426614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Environmental+Science+and+Health%2C+Part+B%3A+Pesticides%2C+Food+Contaminants+and+Agricultural+Wastes&rft.atitle=Sorption+of+Paraquat+on+Clay+Components+in+Taiwan%27s+Oxisol&rft.au=Hseu%2C+Zeng-Yei%3BJien%2C+Shih-Hao%3BCheng%2C+Shuang-Fu&rft.aulast=Hseu&rft.aufirst=Zeng-Yei&rft.date=2003-07-01&rft.volume=B38&rft.issue=4&rft.spage=441&rft.isbn=&rft.btitle=&rft.title=Journal+of+Environmental+Science+and+Health%2C+Part+B%3A+Pesticides%2C+Food+Contaminants+and+Agricultural+Wastes&rft.issn=03601234&rft_id=info:doi/10.1081%2FPFC-120021664 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2004-01-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Soil; Clay; Organic matter; Adsorption; Herbicides DO - http://dx.doi.org/10.1081/PFC-120021664 ER - TY - JOUR T1 - Electromyographic changes in the gluteus medius during stair ascent and descent in subjects with anterior knee pain AN - 19252274; 5816633 AB - Ascending and descending stairs is a provocative activity for anterior knee pain (AKP) patients. The gluteus medius (GM) acts on the lower extremity in the frontal plane and can affect forces at the knee. Determining activation patterns of the GM in patients with AKP can help identify efficacy of training the GM in this population. This study examined electromyographic (EMG) firing patterns in lower extremity muscles in subjects with AKP while ascending and descending stairs. Subjects in the AKP group (n=16) demonstrated general AKP for at least 2 months compared to the control group (n=12); neither group had any history of knee trauma. Subjects were instrumented with EMG electrodes on the vastus medialis oblique (VMO), vastus lateralis (VL), and GM. Retroreflective markers were placed on lower extremities to determine knee flexion angle, and frontal plane pelvis orientation at toe contact. Subjects then performed a series of five stair (height=18 cm) ascent and descent trials. Repeated measures analyses of variance were performed on EMG and kinematic variables, between the two groups and between the symptomatic and asymptomatic sides. In the AKP group the GM demonstrated delayed onset and shorter durations for stair ascent and shorter duration during descent. There were no significant differences between sides in the AKP group. Consistent with previous studies, subjects in the AKP group demonstrated no difference in the VMO onsets relative to VL onsets compared to the control group. Changes in neuromuscular activity patterns may be a result of a compensations strategy due to AKP. Training of GM and other hip muscles is warranted during rehabilitation of AKP patients. JF - Knee Surgery, Sports Traumatology, Arthroscopy AU - Brindle, T J AU - Mattacola, C AU - McCrory, J AD - Physical Disabilities Branch, Rehabilitation Medicine Department, Warren Grant Magnuson Clinical Center National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1604, USA Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 244 EP - 251 VL - 11 IS - 4 SN - 0942-2056, 0942-2056 KW - Physical Education Index KW - Pelvis KW - Knees KW - Electromyography KW - Pain KW - Muscles (activity) KW - PE 090:Sports Medicine & Exercise Sport Science UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19252274?accountid=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=Knee+Surgery%2C+Sports+Traumatology%2C+Arthroscopy&rft.atitle=Electromyographic+changes+in+the+gluteus+medius+during+stair+ascent+and+descent+in+subjects+with+anterior+knee+pain&rft.au=Brindle%2C+T+J%3BMattacola%2C+C%3BMcCrory%2C+J&rft.aulast=Brindle&rft.aufirst=T&rft.date=2003-07-01&rft.volume=11&rft.issue=4&rft.spage=244&rft.isbn=&rft.btitle=&rft.title=Knee+Surgery%2C+Sports+Traumatology%2C+Arthroscopy&rft.issn=09422056&rft_id=info:doi/10.1007%2Fs00167-003-0353-z LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Electromyography; Muscles (activity); Knees; Pain; Pelvis DO - http://dx.doi.org/10.1007/s00167-003-0353-z ER - TY - JOUR T1 - Chlamydia trachomatis, Herpes Simplex Virus 2, and Human T-Cell Lymphotrophic Virus Type 1 Are Not Associated With Grade of Cervical Neoplasia in Jamaican Colposcopy Patients AN - 19229249; 5806856 AB - A few recent studies have suggested that other sexually transmitted infections may increase the likelihood of a human papillomavirus (HPV) infection progressing to high-grade cervical neoplasia and cancer. The goal was to assess whether exposures to Chlamydia trachomatis, human T-cell lymphotrophic virus type 1 (HTLV-I), and/or human simplex virus type 2 (HSV-2) are greater in colposcopy patients with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) than in patients with low-grade cervical neoplasia (CIN1). Sequential patients (n = 447) attending a colposcopy clinic in Kingston, Jamaica, a country with high cervical cancer rates and high HTLV-I prevalence, were tested for (1) HPV DNA by L1 consensus primer (MY09/11) polymerase chain reaction assays, (2) C trachomatis DNA by ligase chain reaction, (3) C trachomatis antibodies by both microimmunofluorescence and a peptide (VS4) enzyme linked immunosorbent assay (ELISA), (4) HTLV-I antibodies by ELISA confirmed by western blotting, and (5) HSV-2 antibodies by a recombinant HSV-2-specific ELISA. Odds ratios and 95% confidence intervals were estimated with use of multinomial logistic regression models. HPV DNA detection was associated with grade of cervical neoplasia but other evaluated sexually transmitted infections were not. HTLV-I, C trachomatis, and/or HSV-2 were not associated with severity of cervical neoplasia in Jamaican women. JF - Sexually Transmitted Diseases AU - Castle, P E AU - Escoffery, C AU - Schachter, J AU - Rattray, C AU - Schiffman, M AU - Moncada, J AU - Sugai, K AU - Brown, C AU - Cranston, B AU - Hanchard, B AU - Palefsky, J M AU - Burk, R D AU - Hutchinson, M L AU - Strickler, H D AD - Division of Cancer Epidemiology and Genetics National Cancer Institute, 6120 Executive Boulevard, MSC 7234, Bethesda, MD 20892, USA, pc95p@nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 575 EP - 580 VL - 30 IS - 7 KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology KW - Enzyme-linked immunosorbent assay KW - Fluorescence KW - Sexually-transmitted diseases KW - Human T-lymphotropic virus 1 KW - Chlamydia trachomatis KW - Jamaica KW - Herpes simplex virus 2 KW - Neoplasia KW - Cervix KW - Colposcopy KW - V 22123:Epidemiology KW - J 02849:Sexually-transmitted diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19229249?accountid=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=Sexually+Transmitted+Diseases&rft.atitle=Chlamydia+trachomatis%2C+Herpes+Simplex+Virus+2%2C+and+Human+T-Cell+Lymphotrophic+Virus+Type+1+Are+Not+Associated+With+Grade+of+Cervical+Neoplasia+in+Jamaican+Colposcopy+Patients&rft.au=Castle%2C+P+E%3BEscoffery%2C+C%3BSchachter%2C+J%3BRattray%2C+C%3BSchiffman%2C+M%3BMoncada%2C+J%3BSugai%2C+K%3BBrown%2C+C%3BCranston%2C+B%3BHanchard%2C+B%3BPalefsky%2C+J+M%3BBurk%2C+R+D%3BHutchinson%2C+M+L%3BStrickler%2C+H+D&rft.aulast=Castle&rft.aufirst=P&rft.date=2003-07-01&rft.volume=30&rft.issue=7&rft.spage=575&rft.isbn=&rft.btitle=&rft.title=Sexually+Transmitted+Diseases&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human T-lymphotropic virus 1; Herpes simplex virus 2; Chlamydia trachomatis; Jamaica; Cervix; Sexually-transmitted diseases; Neoplasia; Fluorescence; Enzyme-linked immunosorbent assay; Colposcopy ER - TY - JOUR T1 - Cancer gene therapy: an awkward adolescence AN - 18943650; 5709216 AB - At the Eleventh International Conference on Gene Therapy of Cancer (December 12-14, 2002, San Diego, CA) progress on using gene transfer technology to treat cancer was presented. Although there is as yet no cancer gene therapy being marketed, considerable progress has been made in defining likely strategies and likely targets for gene therapy of cancer. These strategies, including viral and non-viral delivery systems, and potential targets in cancer cells linked to our developing knowledge of cancer cell biology, are reviewed in this paper. Use of gene therapy to sensitize tumors to radiation and chemotherapy is one promising area of investigation. Some of the ancillary benefits of research on cancer gene therapy, including the development of public-private partnerships, recruitment of laboratory scientists into clinical research, and credentialing of potential cancer cell targets for therapies other than gene therapy, are noted. JF - Cancer Gene Therapy AU - Gottesman, M M AD - Laboratory of Cell Biology, Center for Cancer Research, NCI/NIH, Department of Health and Human Services, Building 37, Room 1A09, Bethesda, MD 20892, USA, mgottesman@nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 501 EP - 508 VL - 10 IS - 7 SN - 0929-1903, 0929-1903 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Reviews KW - Tumors KW - Cancer KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18943650?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Gene+Therapy&rft.atitle=Cancer+gene+therapy%3A+an+awkward+adolescence&rft.au=Gottesman%2C+M+M&rft.aulast=Gottesman&rft.aufirst=M&rft.date=2003-07-01&rft.volume=10&rft.issue=7&rft.spage=501&rft.isbn=&rft.btitle=&rft.title=Cancer+Gene+Therapy&rft.issn=09291903&rft_id=info:doi/10.1038%2Fsj.cgt.7700602 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene therapy; Cancer; Reviews; Tumors DO - http://dx.doi.org/10.1038/sj.cgt.7700602 ER - TY - JOUR T1 - Importance of hydroxyapatite particles characteristics on cytokines production by human monocytes in vitro AN - 18917919; 5611849 AB - Calcium phosphate bioceramics have been applied as bone substitutes for several decades. Aseptic loosening after total joint arthroplasty is a major problem in orthopaedic surgery. Hydroxyapatite particles from materials wear have been reported as the main cause of implant failure. For this reason, an investigation into possible wear particles from materials used in the implant may lead to longevity after arthroplasty. Monocytes are among the first cells to colonize the inflammatory site. In the present study, we have evaluated the inflammatory response after exposition to particles with different characteristics (size, sintering temperature and shape). Our data demonstrate that the most important characteristic was the shape and the size of the particles. The needle shaped particles induced the larger production of TNF- alpha , IL-6 and IL-10 by cells. To a less manner, the smallest particles induced an increase of the expression and production of the cytokines studied (TNF- alpha , IL-6 and IL-10). The sintering temperature appeared to be a less important characteristic even though it was involved in the dissolution/precipitation process. JF - Biomaterials AU - Laquerriere, P AU - Grandjean-Laquerriere, A AU - Jallot, E AU - Balossier, G AU - Frayssinet, P AU - Guenounou, M AD - Laboratoire de Micoscopie Electronique, UFR Sciences, IFR 53, 21, rue Clement Ader, BP 138, 51685, Reims, Cedex 2, France, laquerrp@ors.od.nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 2739 EP - 2747 VL - 24 IS - 16 SN - 0142-9612, 0142-9612 KW - man KW - hydroxyapatite KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Interleukin 6 KW - Tumor necrosis factor KW - Biomaterials KW - Cytokines KW - Monocytes KW - Precipitation KW - Interleukin 10 KW - Arthroplasty KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18917919?accountid=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=Biomaterials&rft.atitle=Importance+of+hydroxyapatite+particles+characteristics+on+cytokines+production+by+human+monocytes+in+vitro&rft.au=Laquerriere%2C+P%3BGrandjean-Laquerriere%2C+A%3BJallot%2C+E%3BBalossier%2C+G%3BFrayssinet%2C+P%3BGuenounou%2C+M&rft.aulast=Laquerriere&rft.aufirst=P&rft.date=2003-07-01&rft.volume=24&rft.issue=16&rft.spage=2739&rft.isbn=&rft.btitle=&rft.title=Biomaterials&rft.issn=01429612&rft_id=info:doi/10.1016%2FS0142-9612%2803%2900089-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Arthroplasty; Precipitation; Monocytes; Cytokines; Tumor necrosis factor; Interleukin 6; Interleukin 10; Biomaterials DO - http://dx.doi.org/10.1016/S0142-9612(03)00089-9 ER - TY - JOUR T1 - Maturation of the Coxiella burnetii parasitophorous vacuole requires bacterial protein synthesis but not replication AN - 18860159; 5698331 AB - This study examined whether protein synthesis and replication are required for maturation and fusogenicity of the lysosomal-like, large and spacious parasitophorous vacuole (PV) of Coxiella bumetii, an obligate intracellular bacterium. Large and spacious PV with multiple non-replicating C. bumetii were observed by phase microscopy in Vero cells infected at a multiplicity of infection of ten and treated with a bacteriostatic concentration of nalidixic acid or carbenicillin, antimicrobics that inhibit DNA and cell wall biosynthesis respectively. Conversely, large and spacious PV were not observed in cells treated with a bacteriostatic concentration of the protein synthesis inhibitor chloramphenicol. Rather, fluorescence microscopy of individual cells revealed multiple, acidic PV harbouring a single organism tightly bounded by a LAMP-1 positive vacuolar membrane. These vacuoles homotypically fused to form a large and spacious PV upon removal of the drug. Chloramphenicol also inhibited trafficking of latex beads to large and spacious PV and caused mature PV to collapse. Collectively, these results demonstrate that C. bumetii protein synthesis, but not replication, is required for fusion between nascent C. bumetii PV and latex bead phagosomes, and also for formation and maintenance of large and spacious, replicative PV. However, transit of nascent PV through the endocytic pathway to ultimately acquire lysosomal markers appears to occur irrespective of Coxiella protein synthesis. JF - Cellular Microbiology AU - Howe, D AU - Melnicakova, J AU - Barak, I AU - Heinzen, R A AD - Department of Molecular Biology, University of Wyoming, Laramie, Wyoming, 82071-3944, USA, rheinzen@niaid.nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 469 EP - 480 VL - 5 IS - 7 SN - 1462-5814, 1462-5814 KW - Vero cells KW - carbenicillin KW - chloramphenicol KW - nalidixic acid KW - Microbiology Abstracts B: Bacteriology KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18860159?accountid=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=Cellular+Microbiology&rft.atitle=Maturation+of+the+Coxiella+burnetii+parasitophorous+vacuole+requires+bacterial+protein+synthesis+but+not+replication&rft.au=Howe%2C+D%3BMelnicakova%2C+J%3BBarak%2C+I%3BHeinzen%2C+R+A&rft.aulast=Howe&rft.aufirst=D&rft.date=2003-07-01&rft.volume=5&rft.issue=7&rft.spage=469&rft.isbn=&rft.btitle=&rft.title=Cellular+Microbiology&rft.issn=14625814&rft_id=info:doi/10.1046%2Fj.1462-5822.2003.00293.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1462-5822.2003.00293.x ER - TY - JOUR T1 - Neurocognitive Impairment Due to Chronic Alcohol Consumption in an American Indian Community AN - 18819976; 5710912 AB - Studies have shown that clinically ascertained alcoholics tend to have lower scores than nonalcoholics on cognitive performance tests, particularly the Block Design (BD) and Digit Symbol (DS) tests of the Weschler Adult Intelligence Scale-Revised (WAIS-R). The aim of this study was to determine whether similar differences are found in a community sample of Plains Indian men and women with an episodic pattern of drinking and a high lifetime prevalence of alcoholism (71% for men, 44% for women). We administered a truncated form of the WAIS-R to 334 members of a Plains Indian tribe (197 women and 137 men). Blind-rated psychiatric diagnoses were assigned according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III-R) criteria and based on the Schedule for Affective Disorders, Lifetime Version (SADS-L) interview. We compared 68 currently drinking alcoholics (38 men and 30 women), 116 abstaining alcoholics (59 men and 57 women) and 150 nonalcoholics (40 men and 110 women). Current and past heavy drinking had no impact on WAIS-R scores in women. Male alcoholics who were abstinent greater than or equal to 2 years had similar scores to nonalcoholic men. Male current drinkers showed a trend for lower overall verbal and performance (PIQ) scores and BD performance subtest. Further analysis showed that drinking for greater than or equal to 15 years was significantly associated with reduced DS in male current drinkers. These findings suggest that for the men in this community sample, the impact on PIQ is due to the direct effect of chronic alcohol consumption on cognitive performance and is at least partially reversible after 2 years of abstinence. JF - Journal of Studies on Alcohol AU - Harris, C R AU - Albaugh, B AU - Goldman, D AU - Enoch, M-A AD - NIH/NIAAA/DICBR/LNG, 12420 Parklawn Drive, Park 5 Building, Room 451, MSC 8110, Bethesda, MD 20892-8110, USA, charris@niaaa.nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 458 EP - 466 VL - 64 IS - 4 SN - 0096-882X, 0096-882X KW - Native Americans KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18819976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Studies+on+Alcohol&rft.atitle=Neurocognitive+Impairment+Due+to+Chronic+Alcohol+Consumption+in+an+American+Indian+Community&rft.au=Harris%2C+C+R%3BAlbaugh%2C+B%3BGoldman%2C+D%3BEnoch%2C+M-A&rft.aulast=Harris&rft.aufirst=C&rft.date=2003-07-01&rft.volume=64&rft.issue=4&rft.spage=458&rft.isbn=&rft.btitle=&rft.title=Journal+of+Studies+on+Alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The C-Terminal Domain of Salmonella enterica Serovar Typhimurium OmpA Is an Immunodominant Antigen in Mice but Appears To Be Only Partially Exposed on the Bacterial Cell Surface AN - 18805284; 5675871 AB - We examined the way the major outer membrane protein OmpA of Salmonella enterica serovar Typhimurium is recognized by the mouse immune system, by raising a panel of 12 monoclonal antibodies (MAbs) against this protein. Interaction between OmpA and these MAbs is competitively inhibited with several-hundredfold dilutions of mouse polyclonal sera obtained by immunization with live or heat-killed whole cells, suggesting that OmpA is one of the immunodominant antigens of serovar Typhimurium. All of the MAbs were specific for an identical epitope(s) located on the C-terminal domain of OmpA, as indicated by the use of OmpA fragments generated by protease or cyanogen bromide treatment and by competitive inhibition enzyme-linked immunosorbent assay. This epitope was highly conserved within (but not outside) the family Enterobacteriaceae. The strong immunogenicity of this epitope was surprising because the C-terminal domain of OmpA, usually thought to be located in the periplasm, is not expected to be exposed on the bacterial cell surface. A MAb, however, reacted in a cytofluorometry assay more strongly with outer-membrane-permeabilized cells than with untreated cells, a result supporting the predominantly periplasmic localization of the epitope. Significant, though low-level, reactivity of intact cells nevertheless suggests that in some cells the C-terminal domain of OmpA is exposed on the surface, a result consistent with the proposal that OmpA can fold into one of the two alternate conformations. JF - Infection and Immunity AU - Singh, S P AU - Williams, YU AU - Miller, S AU - Nikaido, H AD - Office of Scientific Review, National Institute of General Medical Sciences, National Institutes of Health, 45 Center Drive, Room 3AN.12, Bethesda, MD 20892- 6200, Singhs@nigms.nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 3937 EP - 3946 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 71 IS - 7 SN - 0019-9567, 0019-9567 KW - OmpA protein KW - mice KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02832:Antigenic properties and virulence KW - F 06008:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18805284?accountid=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=The+C-Terminal+Domain+of+Salmonella+enterica+Serovar+Typhimurium+OmpA+Is+an+Immunodominant+Antigen+in+Mice+but+Appears+To+Be+Only+Partially+Exposed+on+the+Bacterial+Cell+Surface&rft.au=Singh%2C+S+P%3BWilliams%2C+YU%3BMiller%2C+S%3BNikaido%2C+H&rft.aulast=Singh&rft.aufirst=S&rft.date=2003-07-01&rft.volume=71&rft.issue=7&rft.spage=3937&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.71.7.3937-3946.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.71.7.3937-3946.2003 ER - TY - JOUR T1 - Monitoring human radiation exposure by gene expression profiling: Possibilities and pitfalls AN - 18799581; 5661570 AB - Advances in high throughput analysis of mRNA expression have made it possible to establish gene expression profiles for different cells, tissues, diseases and exposure states. For instance, recent studies have demonstrated the utility of such an approach to classify sub-types of cancers with more detail than was previously possible. In addition, gene expression studies of ionizing radiation exposure both in vitro and in vivo are affording insight into the molecular mechanisms of mammalian radiation response. We have demonstrated that radiation expression profiles are a good predictor of p53 function in cell lines, and such profiles also indicate a major role for p53-regulated genes in the in vivo radiation response. Gene expression can be a sensitive indicator of radiation response as we have shown linear dose-responses for induction of several genes down to doses as low as 2 cGy. As profiles are established from radiation studies, it is hoped that they may be useful for identifying individuals with specific exposures or predisposition to negative outcome of exposure. Although this technology holds great promise, some obstacles remain to be overcome before it can be successfully applied to population studies. JF - Health Physics AU - Amundson, SA AU - Fornace, AJ Jr AD - Gene Response Section, National Cancer Institute, NIH, 37 Convent Drive, Bldg. 37, Rm. 6144, Bethesda, MD 20892, USA, amundson@mail.nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 36 EP - 42 VL - 85 IS - 1 SN - 0017-9078, 0017-9078 KW - man KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14510:Occurrence, isolation & assay KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18799581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Physics&rft.atitle=Monitoring+human+radiation+exposure+by+gene+expression+profiling%3A+Possibilities+and+pitfalls&rft.au=Amundson%2C+SA%3BFornace%2C+AJ+Jr&rft.aulast=Amundson&rft.aufirst=SA&rft.date=2003-07-01&rft.volume=85&rft.issue=1&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Health+Physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Statistical design of reverse dye microarrays AN - 18739659; 5619982 AB - In cDNA microarray experiments all samples are labelled with either Cy3 dye or Cy5 dye. Certain genes exhibit dye bias: a tendency to bind more efficiently to one of the dyes. The common reference design avoids the problem of dye bias by running all arrays 'forward', so that the samples being compared are always labelled with the same dye. But comparison of samples labelled with different dyes is sometimes of interest. In these situations, it is necessary to run some arrays 'reverse': with the dye labelling reversed: in order to correct for the dye bias. The design of these experiments will impact one's ability to identify genes that are differentially expressed in different tissues or conditions. We address the design issue of how many specimens are needed, how many forward and reverse labelled arrays to perform, and how to optimally assign Cy3 and Cy5 labels to the specimens. JF - Bioinformatics AU - Dobbin, K AU - Shih, J H AU - Simon, R AD - National Cancer Institute, Biometric Research Branch, 6130 Executive Blvd., MSC 7434, Bethesda, MD 20892, USA Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 803 EP - 810 VL - 19 IS - 7 SN - 1367-4803, 1367-4803 KW - DNA microarrays KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18739659?accountid=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=Statistical+design+of+reverse+dye+microarrays&rft.au=Dobbin%2C+K%3BShih%2C+J+H%3BSimon%2C+R&rft.aulast=Dobbin&rft.aufirst=K&rft.date=2003-07-01&rft.volume=19&rft.issue=7&rft.spage=803&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 ER - TY - JOUR T1 - Reconstituted 3-dimensional human skin of various ethnic origins as an in vitro model for studies of pigmentation AN - 17851467; 5665406 AB - Reconstituted 3-dimensional human skin equivalents containing melanocytes and keratinocytes on an artificial dermal substitute are gaining popularity for studies of skin metabolism because they exhibit morphological and growth characteristics similar to human epidermis. In this study, we show that such a pigmented epidermis model can be used to assess the regulation of pigmentation by known melanogenic compounds. In monolayers or in melanocyte-keratinocyte co- cultures, melanocyte-keratinocyte interactions are missing or are spatially limited. The commercial skin equivalents used in this study were derived from epidermal cells obtained from donors of three different ethnic origins (African- American, Asian, and Caucasian), and they reflect those distinct skin phenotypes. We used these pigmented human epidermis models to test compounds for potential effects on pigmentation in a more physiologically relevant context, which allows further characterization and validation of interesting melanogenic factors. We used known melanogenic stimulators ( alpha -melanocyte-stimulating hormone and 3,4-dihydroxyphenylalanine) and inhibitors (hydroquinone, arbutin, kojic acid, and niacinamide) and examined their effects on the production of melanin and its distribution in upper layers of the skin. Our studies indicate that commercial skin equivalents provide a convenient and cost-effective alternative to animal testing for evaluating the regulation of mammalian pigmentation by melanogenic factors and for elucidating their mechanisms of action. JF - Analytical Biochemistry AU - Yoon, T-J AU - Lei, T C AU - Yamaguchi, Y AU - Batzer, J AU - Wolber, R AU - Hearing, V J AD - Pigment Cell Biology Section, Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, hearingv@nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 260 EP - 269 PB - Academic Press, Inc., 525 B St. Ste. 1900 San Diego CA 92101-4495 USA, [mailto:apsubs@acad.com] VL - 318 IS - 2 SN - 0003-2697, 0003-2697 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - ^a-Melanocyte-stimulating hormone KW - Pigmentation KW - Melanin KW - Skin KW - Hydroquinone KW - Cell culture KW - Melanocytes KW - Epidermis KW - Kojic acid KW - Keratinocytes KW - Ethnic groups KW - Metabolism KW - W 30965:Miscellaneous, Reviews KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17851467?accountid=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=Analytical+Biochemistry&rft.atitle=Reconstituted+3-dimensional+human+skin+of+various+ethnic+origins+as+an+in+vitro+model+for+studies+of+pigmentation&rft.au=Yoon%2C+T-J%3BLei%2C+T+C%3BYamaguchi%2C+Y%3BBatzer%2C+J%3BWolber%2C+R%3BHearing%2C+V+J&rft.aulast=Yoon&rft.aufirst=T-J&rft.date=2003-07-01&rft.volume=318&rft.issue=2&rft.spage=260&rft.isbn=&rft.btitle=&rft.title=Analytical+Biochemistry&rft.issn=00032697&rft_id=info:doi/10.1016%2FS0003-2697%2803%2900172-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Skin; Pigmentation; Epidermis; Melanocytes; Hydroquinone; Metabolism; Cell culture; Kojic acid; Keratinocytes; Melanin; ^a-Melanocyte-stimulating hormone; Ethnic groups DO - http://dx.doi.org/10.1016/S0003-2697(03)00172-6 ER - TY - JOUR T1 - Drosophila microarray platforms AN - 1434027522; 18513447 AB - The advent of high throughput microarrays and the complete sequencing of the Drosophila melanogaster genome have enabled global gene expression analysis in this powerful genetic model organism. Currently, researchers are using three main Drosophila array platform types, with elements composed of cDNA amplicons, oligonucleotides (short and long) or genomic amplicons. This paper provides a broad overview of these platforms JF - Briefings in Functional Genomics and Proteomics AU - Gupta, Vaijayanti AU - Oliver, Brian AD - A postdoctoral fellow in the Laboratory of Cellular and Developmental Biology, National Institute of Diabetes, Digestive Diseases and Kidney Diseases, National Institutes of Health, Bethesda, Department of Health and Human Services MD, USA., oliver@helix.nih.gov Y1 - 2003/07// PY - 2003 DA - Jul 2003 SP - 97 EP - 105 PB - Oxford University Press VL - 2 IS - 2 SN - 1473-9550, 1473-9550 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Gene expression KW - Reviews KW - Drosophila melanogaster KW - proteomics KW - genomics KW - Oligonucleotides KW - Models KW - G 07870:Mammals KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1434027522?accountid=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=Briefings+in+Functional+Genomics+and+Proteomics&rft.atitle=Drosophila+microarray+platforms&rft.au=Gupta%2C+Vaijayanti%3BOliver%2C+Brian&rft.aulast=Gupta&rft.aufirst=Vaijayanti&rft.date=2003-07-01&rft.volume=2&rft.issue=2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Briefings+in+Functional+Genomics+and+Proteomics&rft.issn=14739550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2013-09-01 N1 - Last updated - 2013-09-20 N1 - SubjectsTermNotLitGenreText - Gene expression; Reviews; genomics; proteomics; Oligonucleotides; Models; Drosophila melanogaster ER - TY - JOUR T1 - Phosphorylation of the head domain of neurofilament protein (NF-M): a factor regulating topographic phosphorylation of NF-M tail domain KSP sites in neurons. AN - 73419737; 12695506 AB - In neurons the phosphorylation of neurofilament (NF) proteins NF-M and NF-H is topographically regulated. Although kinases and NF subunits are synthesized in cell bodies, extensive phosphorylation of the KSP repeats in tail domains of NF-M and NF-H occurs primarily in axons. The nature of this regulation, however, is not understood. As obligate heteropolymers, NF assembly requires interactions between the core NF-L with NF-M or NF-H subunits, a process inhibited by NF head domain phosphorylation. Phosphorylation of head domains at protein kinase A (PKA)-specific sites seems to occur transiently in cell bodies after NF subunit synthesis. We have proposed that transient phosphorylation of head domains prevents NF assembly in the soma and inhibits tail domain phosphorylation; i.e. assembly and KSP phosphorylation in axons depends on prior dephosphorylation of head domain sites. Deregulation of this process leads to pathological accumulations of phosphorylated NFs in the soma as seen in some neurodegenerative disorders. To test this hypothesis, we studied the effect of PKA phosphorylation of the NF-M head domain on phosphorylation of tail domain KSP sites. In rat cortical neurons we showed that head domain phosphorylation of endogenous NF-M by forskolin-activated PKA inhibits NF-M tail domain phosphorylation. To demonstrate the site specificity of PKA phosphorylation and its effect on tail domain phosphorylation, we transfected NIH3T3 cells with NF-M mutated at PKA-specific head domain serine residues. Epidermal growth factor stimulation of cells with mutant NF-M in the presence of forskolin exhibited no inhibition of NF-tail domain phosphorylation compared with the wild type NF-M-transfected cells. This is consistent with our hypothesis that transient phosphorylation of NF-M head domains inhibits tail domain phosphorylation and suggests this as one of several mechanisms underlying topographic regulation. JF - The Journal of biological chemistry AU - Zheng, Ya-Li AU - Li, Bing-Sheng AU - Veeranna AU - Pant, Harish C AD - Laboratory of Neurochemistry, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/06/27/ PY - 2003 DA - 2003 Jun 27 SP - 24026 EP - 24032 VL - 278 IS - 26 SN - 0021-9258, 0021-9258 KW - Neurofilament Proteins KW - 0 KW - neurofilament protein M KW - 111365-29-8 KW - Colforsin KW - 1F7A44V6OU KW - Epidermal Growth Factor KW - 62229-50-9 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - 3T3 Cells KW - Colforsin -- pharmacology KW - Phosphorylation KW - Cerebellar Cortex -- cytology KW - Transfection KW - Mice KW - Epidermal Growth Factor -- pharmacology KW - Repetitive Sequences, Nucleic Acid KW - Protein Structure, Tertiary KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Neurons -- chemistry KW - Neurofilament Proteins -- metabolism KW - Neurofilament Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73419737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phosphorylation+of+the+head+domain+of+neurofilament+protein+%28NF-M%29%3A+a+factor+regulating+topographic+phosphorylation+of+NF-M+tail+domain+KSP+sites+in+neurons.&rft.au=Zheng%2C+Ya-Li%3BLi%2C+Bing-Sheng%3BVeeranna%3BPant%2C+Harish+C&rft.aulast=Zheng&rft.aufirst=Ya-Li&rft.date=2003-06-27&rft.volume=278&rft.issue=26&rft.spage=24026&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 - 2003-08-20 N1 - Date created - 2003-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A newly discovered cholesteryl galactoside from Borrelia burgdorferi AN - 18791692; 5667368 AB - Two major glycolipids, which comprise [approx]36% of the total lipid mass from Borrelia burgdorferi, the etiological agent of Lyme disease, were investigated. We determined the fatty acid type, sugar identity, anomeric configuration, and substituent type and position. The structures were identified as cholesteryl 6-O-acyl- beta -D-galactopyranoside (B. burgdorferi glycolipid 1, BbGL-I), and 1,2-di-O-acyl-3-O- alpha -D-galactopyranosyl-sn-glycerol (BbGL-II). The major fatty acids were palmitate and oleate. The structures were corroborated by gas-liquid chromatography MS, matrix-assisted laser desorption/ionization time-of-flight spectroscopy, fast atom bombardment MS, detailed NMR spectrometry, and metabolic labeling. This is a previously undescribed demonstration of a cholesteryl galactoside in bacteria. Lipopolysaccharide was not detected in B. burgdorferi. The two glycolipids have several properties suggesting they may function as lipopolysaccharide: both are main components of the bacterial membrane, surface exposed, and have a three-domain structure. BbGL-I elicited specific antibodies in mice and rabbits, and BbGL-II elicited antibodies that reacted with both glycolipids. JF - Proceedings of the National Academy of Sciences, USA AU - Ben-Menachem, G AU - Kubler-Kielb, J AU - Coxon, B AU - Yergey, A AU - Schneerson, R AD - Laboratories of Developmental and Molecular Immunity, and Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, gilben@nih.gov Y1 - 2003/06/24/ PY - 2003 DA - 2003 Jun 24 SP - 7913 EP - 7918 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 13 SN - 0027-8424, 0027-8424 KW - cholesteryl galactoside KW - mice KW - Microbiology Abstracts B: Bacteriology KW - J 02731:Lipids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18791692?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=A+newly+discovered+cholesteryl+galactoside+from+Borrelia+burgdorferi&rft.au=Ben-Menachem%2C+G%3BKubler-Kielb%2C+J%3BCoxon%2C+B%3BYergey%2C+A%3BSchneerson%2C+R&rft.aulast=Ben-Menachem&rft.aufirst=G&rft.date=2003-06-24&rft.volume=100&rft.issue=13&rft.spage=7913&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.1232451100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.1232451100 ER - TY - JOUR T1 - Red cell perturbations by amyloid beta-protein. AN - 73407778; 12829257 AB - Amyloid beta-protein (A beta) accumulation in brain is thought to be important in causing the neuropathology of Alzheimer's disease (AD). A beta interactions with both neurons and microglial cells play key roles in AD. Since vascular deposition of A beta is also implicated in AD, the interaction of red cells with these toxic aggregates gains importance. However, the effects of A beta interactions with red blood cells are less well understood. Synthetic amyloid beta-protein (1-40) was labeled with biotin and preincubated at 37 degrees C for 4, 14 and 72 h to produce fibrils. Flow cytometry was used to study the binding of these fibrils to red cells. The amyloid fibrils had a high affinity for the red cell with increased binding for the larger fibrils produced by longer preincubation. Bovine serum albumin (BSA) did not reverse the binding, but actually resulted in a more efficient binding of the A beta fibrils to the red cells. The interaction of A beta with red cells increased the mean cell volume and caused the cells to become more spherical. This effect was greater for the longer fibrils. At the same time the interaction of A beta with red cells produced an increase in their fluorescence measured after 16-h incubation at 37 degrees C. This increase in fluorescence is attributed to the formation of fluorescent heme degradation products. The effect of prior hemoglobin oxidation, catalase inhibition and glutathione peroxidase inhibition indicated that the amyloid-induced oxidative damage to the red cell involved hydrogen peroxide-induced heme degradation. These results suggest that amyloid interactions with the red cell may contribute to the pathology of AD. JF - Biochimica et biophysica acta AU - Jayakumar, Rajadas AU - Kusiak, John W AU - Chrest, Francis J AU - Demehin, Andrew A AU - Murali, Jayaraman AU - Wersto, Robert P AU - Nagababu, Enika AU - Ravi, Lukebabu AU - Rifkind, Joseph M AD - Molecular Dynamics Section, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003/06/20/ PY - 2003 DA - 2003 Jun 20 SP - 20 EP - 28 VL - 1622 IS - 1 SN - 0006-3002, 0006-3002 KW - Amyloid beta-Peptides KW - 0 KW - Index Medicus KW - Oxidation-Reduction KW - Humans KW - Oxidative Stress KW - Alzheimer Disease -- etiology KW - Erythrocytes -- drug effects KW - Amyloid beta-Peptides -- metabolism KW - Amyloid beta-Peptides -- toxicity KW - Erythrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73407778?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Red+cell+perturbations+by+amyloid+beta-protein.&rft.au=Jayakumar%2C+Rajadas%3BKusiak%2C+John+W%3BChrest%2C+Francis+J%3BDemehin%2C+Andrew+A%3BMurali%2C+Jayaraman%3BWersto%2C+Robert+P%3BNagababu%2C+Enika%3BRavi%2C+Lukebabu%3BRifkind%2C+Joseph+M&rft.aulast=Jayakumar&rft.aufirst=Rajadas&rft.date=2003-06-20&rft.volume=1622&rft.issue=1&rft.spage=20&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 - 2003-08-01 N1 - Date created - 2003-06-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term safety analysis of preventive HIV-1 vaccines evaluated in AIDS vaccine evaluation group NIAID-sponsored Phase I and II clinical trials. AN - 73361940; 12798637 AB - This report evaluates long-term safety data from 3189 human immunodeficiency virus type 1 (HIV-1) uninfected, healthy volunteers who were enrolled into 51 National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Phase I and II multicentred, randomized, double-blind trials of recombinant HIV-1 subunit vaccines (23 studies), synthetic peptide vaccines (7 studies), live vaccinia-vector recombinant envelope vaccines (7 studies), canarypox vector recombinant vaccines (13 studies), a DNA vaccine (1 study), and a Salmonella-vector vaccine (1 study). During the 12,340 person-years of follow-up, participants were monitored for adverse events including immune dysfunction/autoimmunity, anaphylaxis, cancer, death, and vaccine allergy. The analysis provides evidence that a preparation of a C4-V3 polypeptide vaccine emulsified in incomplete Freund's caused serious toxicity, but otherwise no safety problems considered serious were identified for any of the vaccines and adjuvants studied. These data serve to solidify the growing safety base of current vaccine technologies utilized in candidate vaccines for HIV-1 infection. JF - Vaccine AU - Gilbert, P B AU - Chiu, Y-L AU - Allen, M AU - Lawrence, D N AU - Chapdu, C AU - Israel, H AU - Holman, D AU - Keefer, M C AU - Wolff, M AU - Frey, S E AU - NIAID HIV Vaccine Trials Network AD - Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA, USA. ; NIAID HIV Vaccine Trials Network Y1 - 2003/06/20/ PY - 2003 DA - 2003 Jun 20 SP - 2933 EP - 2947 VL - 21 IS - 21-22 SN - 0264-410X, 0264-410X KW - AIDS Vaccines KW - 0 KW - Vaccines, Subunit KW - Vaccines, Synthetic KW - Index Medicus KW - United States KW - Vaccinia virus -- genetics KW - Vaccinia virus -- immunology KW - Salmonella -- genetics KW - Randomized Controlled Trials as Topic KW - Clinical Trials, Phase II as Topic KW - Double-Blind Method KW - Canarypox virus -- immunology KW - Humans KW - Vaccines, Subunit -- adverse effects KW - Canarypox virus -- genetics KW - Time KW - Clinical Trials, Phase I as Topic KW - Adult KW - National Institutes of Health (U.S.) KW - Vaccines, Synthetic -- genetics KW - Middle Aged KW - Vaccines, Synthetic -- adverse effects KW - Adolescent KW - Salmonella -- immunology KW - Female KW - Male KW - HIV-1 -- immunology KW - AIDS Vaccines -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73361940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Long-term+safety+analysis+of+preventive+HIV-1+vaccines+evaluated+in+AIDS+vaccine+evaluation+group+NIAID-sponsored+Phase+I+and+II+clinical+trials.&rft.au=Gilbert%2C+P+B%3BChiu%2C+Y-L%3BAllen%2C+M%3BLawrence%2C+D+N%3BChapdu%2C+C%3BIsrael%2C+H%3BHolman%2C+D%3BKeefer%2C+M+C%3BWolff%2C+M%3BFrey%2C+S+E%3BNIAID+HIV+Vaccine+Trials+Network&rft.aulast=Gilbert&rft.aufirst=P&rft.date=2003-06-20&rft.volume=21&rft.issue=21-22&rft.spage=2933&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-06 N1 - Date created - 2003-06-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dehydroepiandrosterone inhibits the expression of carcinogen-activating enzymes in vivo. AN - 73232578; 12704664 AB - We investigated the effect of the steroid hormone dehydroepiandrosterone (DHEA) on the hepatic expression and activity of carcinogen-activating enzymes, the cytochromes P450 (CYP) 1A1, 1A2 and 1B1, in Sprague-Dawley rats. In animals fed DHEA at 200 or 400 mg/kg body weight every other day for 2 weeks prior to exposure to the aryl hydrocarbon dimethylbenz[a]anthracene (DMBA, 5 mg/kg), there was a dose-dependent decrease in hepatic CYP activity, as measured by ethoxyresorufin-O (EROD) assay, from 37.1 to 22.9 and 14.7 pmoles/min/10 microg microsomes, respectively. DHEA did not directly inhibit microsomal EROD activity, however, leading us to investigate its effects on enzyme expression. To test this, we examined protein and mRNA levels of the enzymes. Western blot for CYP1A1 and CYP1A2 showed that DHEA inhibited the increase in hepatic CYP1A1 and CYP1A2 enzyme levels that are normally induced by DMBA. DMBA-induced increase in expression of CYP1A1, CYP1A2 and CYP1B1 mRNA was similarly blunted in DHEA-treated animals. DHEA was also able to significantly reduce the basal expression of CYP1A1 and CYP1A2 but not of CYP1B1. These results indicate that DHEA regulates the expression and, hence, the activity of hepatic carcinogen-activating enzymes in vivo, and this may be an important mechanism of its chemopreventive activity. JF - International journal of cancer AU - Ciolino, Henry AU - MacDonald, Chistopher AU - Memon, Omar AU - Dankwah, Maame AU - Yeh, Grace Chao AD - Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, National Cancer Institute at Frederick, Frederick, MD, USA. hciolino@ncifcrf.gov Y1 - 2003/06/20/ PY - 2003 DA - 2003 Jun 20 SP - 321 EP - 325 VL - 105 IS - 3 SN - 0020-7136, 0020-7136 KW - Adjuvants, Immunologic KW - 0 KW - Anticarcinogenic Agents KW - RNA, Messenger KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cyp1b1 protein, rat KW - Cytochrome P-450 CYP1A1 KW - Cytochrome P-450 CYP1A2 KW - Cytochrome P-450 CYP1B1 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Blotting, Western KW - RNA, Messenger -- metabolism KW - Dose-Response Relationship, Drug KW - Microsomes -- metabolism KW - Body Weight -- drug effects KW - Reverse Transcriptase Polymerase Chain Reaction KW - Female KW - Cytochrome P-450 CYP1A1 -- pharmacology KW - Anticarcinogenic Agents -- pharmacology KW - Adjuvants, Immunologic -- pharmacology KW - Dehydroepiandrosterone -- pharmacology KW - Cytochrome P-450 CYP1A2 -- biosynthesis KW - Cytochrome P-450 CYP1A1 -- biosynthesis KW - Aryl Hydrocarbon Hydroxylases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73232578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dehydroepiandrosterone+inhibits+the+expression+of+carcinogen-activating+enzymes+in+vivo.&rft.au=Ciolino%2C+Henry%3BMacDonald%2C+Chistopher%3BMemon%2C+Omar%3BDankwah%2C+Maame%3BYeh%2C+Grace+Chao&rft.aulast=Ciolino&rft.aufirst=Henry&rft.date=2003-06-20&rft.volume=105&rft.issue=3&rft.spage=321&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 - 2003-06-16 N1 - Date created - 2003-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Classifying the precancers: a metadata approach. AN - 71317144; 12818004 AB - During carcinogenesis, precancers are the morphologically identifiable lesions that precede invasive cancers. In theory, the successful treatment of precancers would result in the eradication of most human cancers. Despite the importance of these lesions, there has been no effort to list and classify all of the precancers. The purpose of this study is to describe the first comprehensive taxonomy and classification of the precancers. As a novel approach to disease classification, terms and classes were annotated with metadata (data that describes the data) so that the classification could be used to link precancer terms to data elements in other biological databases. Terms in the UMLS (Unified Medical Language System) related to precancers were extracted. Extracted terms were reviewed and additional terms added. Each precancer was assigned one of six general classes. The entire classification was assembled as an XML (eXtensible Mark-up Language) file. A Perl script converted the XML file into a browser-viewable HTML (HyperText Mark-up Language) file. The classification contained 4700 precancer terms, 568 distinct precancer concepts and six precancer classes: 1) Acquired microscopic precancers; 2) acquired large lesions with microscopic atypia; 3) Precursor lesions occurring with inherited hyperplastic syndromes that progress to cancer; 4) Acquired diffuse hyperplasias and diffuse metaplasias; 5) Currently unclassified entities; and 6) Superclass and modifiers. This work represents the first attempt to create a comprehensive listing of the precancers, the first attempt to classify precancers by their biological properties and the first attempt to create a pathologic classification of precancers using standard metadata (XML). The classification is placed in the public domain, and comment is invited by the authors, who are prepared to curate and modify the classification. JF - BMC medical informatics and decision making AU - Berman, Jules J AU - Henson, Donald E AD - Cancer Diagnosis Program, National Cancer Institute, NIH, Rockville, Maryland, USA. bermanj@mail.nih.gov Y1 - 2003/06/20/ PY - 2003 DA - 2003 Jun 20 SP - 8 VL - 3 KW - Index Medicus KW - Programming Languages KW - Humans KW - Decision Support Systems, Clinical KW - Internet KW - Precancerous Conditions -- classification KW - Unified Medical Language System -- trends KW - Precancerous Conditions -- diagnosis KW - Medical Informatics -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71317144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+medical+informatics+and+decision+making&rft.atitle=Classifying+the+precancers%3A+a+metadata+approach.&rft.au=Berman%2C+Jules+J%3BHenson%2C+Donald+E&rft.aulast=Berman&rft.aufirst=Jules&rft.date=2003-06-20&rft.volume=3&rft.issue=&rft.spage=8&rft.isbn=&rft.btitle=&rft.title=BMC+medical+informatics+and+decision+making&rft.issn=1472-6947&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-09 N1 - Date created - 2003-10-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Clin Cancer Res. 2002 Feb;8(2):314-46 [11839647] Mod Pathol. 1993 Sep;6(5):544-54 [8248110] Cell Prolif. 1992 Nov;25(6):549-57 [1457604] Nature. 2002 Sep 26;419(6905):337 [12353005] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of Insertion into Secondary Attachment Sites by Phage lambda and by int Mutants with Altered Recombination Specificity AN - 18789296; 5656921 AB - When phage lambda lysogenizes a cell that lacks the primary bacterial attachment site, integrase catalyzes insertion of the phage chromosome into one of many secondary sites. Here, we characterize the secondary sites that are preferred by wild-type lambda and by lambda int mutants with altered insertion specificity. The sequences of these secondary sites resembled that of the primary site: they contained two imperfect inverted repeats flanking a short spacer. The imperfect inverted repeats of the primary site bind integrase, while the 7 bp spacer, or overlap region, swaps strands with a complementary sequence in the phage attachment site during recombination. We found substantial sequence conservation in the imperfect inverted repeats of secondary sites, and nearly perfect conservation in the leftmost three bases of the overlap region. By contrast, the rightmost bases of the overlap region were much more variable. A phage with an altered overlap region preferred to insert into secondary sites with the corresponding bases. We suggest that this difference between the left and right segments is a result of the defined order of strand exchanges during integrase-promoted recombination. This suggestion accounts for the unexpected segregation pattern of the overlap region observed after insertion into several secondary sites. Some of the altered specificity int mutants differed from wild-type in secondary site preference, but we were unable to identify simple sequence motifs that account for these differences. We propose that insertion into secondary sites is a step in the evolutionary change of phage insertion specificity and present a model of how this might occur. JF - Journal of Molecular Biology AU - Rutkai, E AU - Dorgai, L AU - Sirot, R AU - Yagil, E AU - Weisberg, R A AD - Bay Zoltan Institute for Biotechnology, Derkovits Faser 2, H-6726 Szeged, Hungary, rweisberg@nih.gov Y1 - 2003/06/20/ PY - 2003 DA - 2003 Jun 20 SP - 983 EP - 996 VL - 329 IS - 5 SN - 0022-2836, 0022-2836 KW - attachment KW - integrase KW - nucleotide sequence KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07312:Phages KW - J 02750:Phage-host interactions KW - V 22070:Phage-host interactions including lysogeny & transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18789296?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Analysis+of+Insertion+into+Secondary+Attachment+Sites+by+Phage+lambda+and+by+int+Mutants+with+Altered+Recombination+Specificity&rft.au=Rutkai%2C+E%3BDorgai%2C+L%3BSirot%2C+R%3BYagil%2C+E%3BWeisberg%2C+R+A&rft.aulast=Rutkai&rft.aufirst=E&rft.date=2003-06-20&rft.volume=329&rft.issue=5&rft.spage=983&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1016%2FS0022-2836%2803%2900442-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0022-2836(03)00442-X ER - TY - JOUR T1 - Watching a Protein as it Functions with 150-ps Time-Resolved X-ray Crystallography AN - 18777540; 5650566 AB - We report picosecond time-resolved x-ray diffraction from the myoglobin (Mb) mutant in which Leu super(29) is replaced by Phe (L29Fmutant). The frame-by-frame structural evolution, resolved to 1.8 angstroms, allows one to literally "watch" the protein as it executes its function. Time-resolved mid-infrared spectroscopy of flash-photolyzed L29F MbCO revealed a short-lived CO intermediate whose 140-ps lifetime is shorter than that found in wild-type protein by a factor of 1000. The electron density maps of the protein unveil transient conformational changes far more dramatic than the structural differences between the carboxy and deoxy states and depict the correlated side-chain motion responsible for rapidly sweeping CO away from its primary docking site. JF - Science (Washington) AU - Schotte, F AU - Lim, M AU - Jackson, T A AU - Smirnov, A V AU - Soman, J AU - Olson, J S AU - Phillips, GN Jr AU - Wulff, M AU - Anfinrud, P A AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2003/06/20/ PY - 2003 DA - 2003 Jun 20 SP - 1944 EP - 1947 PB - American Association for the Advancement of Science VL - 300 IS - 5627 SN - 0036-8075, 0036-8075 KW - conformational changes KW - electron density mapping KW - myoglobin KW - protein evolution KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Bioengineering Abstracts KW - G 07140:Proteins KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18777540?accountid=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=Science+%28Washington%29&rft.atitle=Watching+a+Protein+as+it+Functions+with+150-ps+Time-Resolved+X-ray+Crystallography&rft.au=Schotte%2C+F%3BLim%2C+M%3BJackson%2C+T+A%3BSmirnov%2C+A+V%3BSoman%2C+J%3BOlson%2C+J+S%3BPhillips%2C+GN+Jr%3BWulff%2C+M%3BAnfinrud%2C+P+A&rft.aulast=Schotte&rft.aufirst=F&rft.date=2003-06-20&rft.volume=300&rft.issue=5627&rft.spage=1944&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Functional tolerance and blockade of long-term depression at synapses in the nucleus accumbens after chronic cannabinoid exposure. AN - 73478060; 12832502 AB - The rewarding properties of the psychoactive constituents of marijuana, termed "cannabinoids," may reflect actions on synaptic transmission in the nucleus accumbens (NAc). Furthermore, long-term changes in these synapses may support the addictive process. Excitatory and inhibitory synapses are acutely inhibited by cannabinoids in the NAc, and endogenous cannabinoids (endocannabinoids) play a critical role in the expression of long-term depression (LTD) of excitatory cortical afferents in this structure. Because humans often use marijuana for prolonged periods, we examined the impact of long-term cannabinoid exposure on synaptic processes in an animal model. Electrophysiological recordings in rat brain slices containing the NAc were performed after chronic exposure to vehicle solution, Delta9-tetrahydrocannabinol (THC), or the cannabinoid agonist R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-(1-naphthalenyl)methanone mesylate (WIN55,212-2). Extracellular glutamatergic postsynaptic potentials and whole-cell GABAergic IPSCs were concentration-dependently inhibited by WIN55,212-2 in slices from naive or vehicle-treated animals. However, the sensitivity to WIN55,212-2 was diminished in chronic agonist-treated animals. In addition, cross-tolerance to the inhibitory effect of the mu-opioid agonist Tyr-D-Ala2, N-CH3-Phe4,Gly-ol-enkephalin was observed. Endocannabinoid-mediated LTD was initiated via electrical stimulation (5 min, 10 Hz) of glutamatergic afferents to the NAc and was completely blocked by the cannabinoid receptor antagonist SR141716A [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide] in vehicle-treated animals. LTD was not observed in brain slices from rats chronically treated with Delta9-THC or WIN55,212-2. These data demonstrate that long-term exposure to the active ingredient of marijuana blocks synaptic plasticity in the NAc and reduces the sensitivity of GABAergic and glutamatergic synapses to both cannabinoids and opioids. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Hoffman, Alexander F AU - Oz, Murat AU - Caulder, Tara AU - Lupica, Carl R AD - Cellular Neurobiology Branch, Section on Cellular Neurophysiology, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, United States Department of Health and Human Services, Baltimore, Maryland 21224, USA. Y1 - 2003/06/15/ PY - 2003 DA - 2003 Jun 15 SP - 4815 EP - 4820 VL - 23 IS - 12 KW - Benzoxazines KW - 0 KW - Cannabinoid Receptor Modulators KW - Cannabinoids KW - Morpholines KW - Naphthalenes KW - Piperidines KW - Pyrazoles KW - Receptors, Cannabinoid KW - Receptors, Drug KW - Receptors, Opioid, mu KW - Win 55212-2 KW - 5H31GI9502 KW - Dronabinol KW - 7J8897W37S KW - rimonabant KW - RML78EN3XE KW - Index Medicus KW - Naphthalenes -- pharmacology KW - Animals KW - Drug Resistance -- physiology KW - Dose-Response Relationship, Drug KW - Dronabinol -- pharmacology KW - Morpholines -- pharmacology KW - Electric Stimulation KW - Rats KW - Piperidines -- pharmacology KW - Pyrazoles -- pharmacology KW - Rats, Sprague-Dawley KW - Time KW - Receptors, Drug -- agonists KW - Patch-Clamp Techniques KW - Receptors, Opioid, mu -- agonists KW - In Vitro Techniques KW - Receptors, Drug -- antagonists & inhibitors KW - Male KW - Marijuana Abuse -- physiopathology KW - Synapses -- physiology KW - Synapses -- drug effects KW - Long-Term Synaptic Depression -- physiology KW - Nucleus Accumbens -- drug effects KW - Drug Tolerance -- physiology KW - Nucleus Accumbens -- physiology KW - Long-Term Synaptic Depression -- drug effects KW - Nucleus Accumbens -- cytology KW - Cannabinoids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73478060?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+tolerance+and+blockade+of+long-term+depression+at+synapses+in+the+nucleus+accumbens+after+chronic+cannabinoid+exposure.&rft.au=Hoffman%2C+Alexander+F%3BOz%2C+Murat%3BCaulder%2C+Tara%3BLupica%2C+Carl+R&rft.aulast=Hoffman&rft.aufirst=Alexander&rft.date=2003-06-15&rft.volume=23&rft.issue=12&rft.spage=4815&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-05 N1 - Date created - 2003-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combination therapy in treatment of experimental pulmonary aspergillosis: synergistic interaction between an antifungal triazole and an echinocandin. AN - 73382202; 12792859 AB - Invasive pulmonary aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Simultaneous inhibition of fungal cell-wall and cell-membrane biosynthesis may result in synergistic interaction against Aspergillus fumigatus. We studied the antifungal activity of micafungin, a new echinocandin, in combination with ravuconazole, a second-generation triazole, against experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. This combination led to significant reductions in mortality (P 3' direction, creating double-stranded DNA with 3' single-stranded DNA tails; and (iii) Beta binds these 3' overhangs to protect and anneal them to complementary sequences. We have tested this model for Red recombination by using electroporation to introduce overlapping, complementary oligonucleotides that when annealed in vivo approximate the recombination intermediate that Exo should create. Using this technique we found Exo-independent recombination. Surprisingly, a similarly constructed substrate with 5' overhangs recombined more efficiently. This 5' overhang recombination required both Exo and Beta for high levels of recombination and the two oligonucleotides need to overlap by only 6 bp on their 3' ends. Results indicate that Exo may load Beta onto the 3' overhang it produces. In addition, multiple overlapping oligonucleotides were successfully used to generate recombinants in vivo, a technique that could prove useful for many genetic engineering procedures. JF - Proceedings of the National Academy of Sciences, USA AU - Yu, D AU - Sawitzke, JA AU - Ellis, H AU - Court, D L AD - Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, National Cancer Institute, P.O. Box B, Frederick, MD 21702, court@ncifcrf.gov Y1 - 2003/06/10/ PY - 2003 DA - 2003 Jun 10 SP - 7207 EP - 7212 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 12 SN - 0027-8424, 0027-8424 KW - Beta protein KW - Exo protein KW - Gam protein KW - electroporation KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14210:Occurrence, isolation & assay KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews KW - W4 320:Cell Culture & Batch Fermentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18806778?accountid=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=Recombineering+with+overlapping+single-stranded+DNA+oligonucleotides%3A+Testing+a+recombination+intermediate&rft.au=Yu%2C+D%3BSawitzke%2C+JA%3BEllis%2C+H%3BCourt%2C+D+L&rft.aulast=Yu&rft.aufirst=D&rft.date=2003-06-10&rft.volume=100&rft.issue=12&rft.spage=7207&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.1232375100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.1232375100 ER - TY - JOUR T1 - Predicting survival in patients with metastatic kidney cancer by gene expression profiling in the primary tumor AN - 17852856; 5667076 AB - To identify potential molecular determinants of tumor biology and possible clinical outcomes, global gene-expression patterns were analyzed in the primary tumors of patients with metastatic renal cell cancer by using cDNA microarrays. We used grossly dissected tumor masses that included tumor, blood vessels, connective tissue, and infiltrating immune cells to obtain a gene-expression "profile" from each primary tumor. Two patterns of gene expression were found within this uniformly staged patient population, which correlated with a significant difference in overall survival between the two patient groups. Subsets of genes most significantly associated with survival were defined, and vascular cell adhesion molecule-1 (VCAM-1) was the gene most predictive for survival. Therefore, despite the complex biological nature of metastatic cancer, basic clinical behavior as defined by survival may be determined by the gene-expression patterns expressed within the compilation of primary gross tumor cells. We conclude that survival in patients with metastatic renal cell cancer can be correlated with the expression of various genes based solely on the expression profile in the primary kidney tumor. JF - Proceedings of the National Academy of Sciences, USA AU - Vasselli, J R AU - Shih, J H AU - Iyengar AU - Maranchie, J AU - Riss, J AU - Worrell, R AU - Torres-Cabala, C AU - Tabios, R AU - Mariotti, A AU - Stearman, R AU - Merino, M AU - Walther, M M AU - Simon, R AU - Klausner, R D AU - Linehan, WM AD - Urologic Oncology Branch, Biometric Research Branch, Laboratory of Biosystems and Cancer, Center for Cancer Research, and Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, uob@mail.nih.gov Y1 - 2003/06/10/ PY - 2003 DA - 2003 Jun 10 SP - 6958 EP - 6963 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 100 IS - 12 SN - 0027-8424, 0027-8424 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Metastases KW - Cell survival KW - Gene expression KW - vascular cell adhesion molecule 1 KW - Blood vessels KW - Connective tissues KW - Kidney KW - Tumor cells KW - DNA microarrays KW - Cancer KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17852856?accountid=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=Predicting+survival+in+patients+with+metastatic+kidney+cancer+by+gene+expression+profiling+in+the+primary+tumor&rft.au=Vasselli%2C+J+R%3BShih%2C+J+H%3BIyengar%3BMaranchie%2C+J%3BRiss%2C+J%3BWorrell%2C+R%3BTorres-Cabala%2C+C%3BTabios%2C+R%3BMariotti%2C+A%3BStearman%2C+R%3BMerino%2C+M%3BWalther%2C+M+M%3BSimon%2C+R%3BKlausner%2C+R+D%3BLinehan%2C+WM&rft.aulast=Vasselli&rft.aufirst=J&rft.date=2003-06-10&rft.volume=100&rft.issue=12&rft.spage=6958&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.1131754100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene expression; Cell survival; Kidney; Cancer; Metastases; vascular cell adhesion molecule 1; DNA microarrays; Connective tissues; Blood vessels; Tumor cells DO - http://dx.doi.org/10.1073/pnas.1131754100 ER - TY - JOUR T1 - Gynaecomastia in men with chronic myeloid leukaemia after imatinib. AN - 73414439; 12801741 AB - cKit and platelet-derived growth-factor receptor (PDGFR) are receptor tyrosine kinases expressed in the testis, are involved in testosterone production, and are inhibited by imatinib. We measured hormone concentrations in 38 men receiving imatinib for chronic myeloid leukaemia at baseline and during treatment. Mean follow-up was 23.6 months (SD 7.5). We noted seven cases of gynaecomastia (18%, 95% CI 6-30%). A comparison of hormone concentrations in 21 patients before and during treatment showed that patients who developed gynaecomastia had a reduction in free testosterone concentrations of 29.53 pmol/L (95% CI 11.63-47.43), while patients who did not had a decrease of 6.36 pmol/L (-1.02 to 13.74). In most men with chronic myeloid leukaemia studied here, imatinib was associated with a reduction in the production of testicular hormones and in some, with the development of gynaecomastia. JF - Lancet (London, England) AU - Gambacorti-Passerini, Carlo AU - Tornaghi, Lucia AU - Cavagnini, Francesco AU - Rossi, Pellegrino AU - Pecori-Giraldi, Francesca AU - Mariani, Luigi AU - Cambiaghi, Nadia AU - Pogliani, Enrico AU - Corneo, Gianmarco AU - Gnessi, Lucio AD - National Cancer Institute, Milan, Italy. carlo.gambacorti@istitutotumori.mi.it Y1 - 2003/06/07/ PY - 2003 DA - 2003 Jun 07 SP - 1954 EP - 1956 VL - 361 IS - 9373 SN - 0140-6736, 0140-6736 KW - Antineoplastic Agents KW - 0 KW - Benzamides KW - Piperazines KW - Pyrimidines KW - Testosterone KW - 3XMK78S47O KW - Progesterone KW - 4G7DS2Q64Y KW - Imatinib Mesylate KW - 8A1O1M485B KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Testosterone -- blood KW - Middle Aged KW - Progesterone -- blood KW - Male KW - Pyrimidines -- adverse effects KW - Pyrimidines -- therapeutic use KW - Piperazines -- therapeutic use KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- blood KW - Gynecomastia -- chemically induced KW - Piperazines -- adverse effects KW - Antineoplastic Agents -- therapeutic use KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- drug therapy KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- complications KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73414439?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gynaecomastia+in+men+with+chronic+myeloid+leukaemia+after+imatinib.&rft.au=Gambacorti-Passerini%2C+Carlo%3BTornaghi%2C+Lucia%3BCavagnini%2C+Francesco%3BRossi%2C+Pellegrino%3BPecori-Giraldi%2C+Francesca%3BMariani%2C+Luigi%3BCambiaghi%2C+Nadia%3BPogliani%2C+Enrico%3BCorneo%2C+Gianmarco%3BGnessi%2C+Lucio&rft.aulast=Gambacorti-Passerini&rft.aufirst=Carlo&rft.date=2003-06-07&rft.volume=361&rft.issue=9373&rft.spage=1954&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-01 N1 - Date created - 2003-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Identifying multilineage mammary epithelial progenitors, in vivo AN - 39785692; 3767950 AU - Smith, G H AU - Wagner, K AU - Boulanger, C Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39785692?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Identifying+multilineage+mammary+epithelial+progenitors%2C+in+vivo&rft.au=Smith%2C+G+H%3BWagner%2C+K%3BBoulanger%2C+C&rft.aulast=Smith&rft.aufirst=G&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society of Cell Biology, 8120 Woodmont Ave., Suite 750, Bethesda MD 20814, USA; phone: 301-347-9300; fax: 301-347-9310; email: ascbinfo@ascb.org; URL: www.ascb.org. Paper No. 2352 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Imaging developing blood vessels in the zebrafish AN - 39704157; 3759122 AU - Weinstein, B Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39704157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Imaging+developing+blood+vessels+in+the+zebrafish&rft.au=Weinstein%2C+B&rft.aulast=Weinstein&rft.aufirst=B&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Association of Anatomists, 9650 Rockville Pike, Bethesda, Maryland 20814-3998, USA; phone: 301-634-7910; fax: 301-634-7965; email: exec@anatomy.org; URL: www.anatomy.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Clearance of bacterial vaginosis and Trichomonas vaginalis among obstetric patients who smoke AN - 39666697; 3769100 AU - Stallings, S P Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39666697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Clearance+of+bacterial+vaginosis+and+Trichomonas+vaginalis+among+obstetric+patients+who+smoke&rft.au=Stallings%2C+S+P&rft.aulast=Stallings&rft.aufirst=S&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Gynecologic Investigation, 409 12th Street, SW, Washington, DC 20024, USA; phone: 202 863-2544; fax: 202 863-0739; URL: sgionline.org. Paper No. #372 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Metastasis-promoting site on Laminin-1 binds a heparan sulfate/chondroitin sulfate-containing proteoglycan on B16-F10 melanoma cells AN - 39664166; 3767789 AU - Engbring, JA Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39664166?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Metastasis-promoting+site+on+Laminin-1+binds+a+heparan+sulfate%2Fchondroitin+sulfate-containing+proteoglycan+on+B16-F10+melanoma+cells&rft.au=Engbring%2C+JA&rft.aulast=Engbring&rft.aufirst=JA&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society of Cell Biology, 8120 Woodmont Ave., Suite 750, Bethesda MD 20814, USA; phone: 301-347-9300; fax: 301-347-9310; email: ascbinfo@ascb.org; URL: www.ascb.org. Paper No. 21 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Opsin point mutations in Drosophila melanogaster and the one-hit model of neuronal degeneration AN - 39654732; 3767862 AU - Sharrow, M AU - DiPietrantonio, A M AU - Davidson, F F Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39654732?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Opsin+point+mutations+in+Drosophila+melanogaster+and+the+one-hit+model+of+neuronal+degeneration&rft.au=Sharrow%2C+M%3BDiPietrantonio%2C+A+M%3BDavidson%2C+F+F&rft.aulast=Sharrow&rft.aufirst=M&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society of Cell Biology, 8120 Woodmont Ave., Suite 750, Bethesda MD 20814, USA; phone: 301-347-9300; fax: 301-347-9310; email: ascbinfo@ascb.org; URL: www.ascb.org. Paper No. 821 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Are maternal cotinine levels associated with spontaneous preterm birth (SPB) or preterm premature rupture of membranes (PPROM)? AN - 39654402; 3769458 AU - Ramsey, P S AU - Hauth, J C Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39654402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Are+maternal+cotinine+levels+associated+with+spontaneous+preterm+birth+%28SPB%29+or+preterm+premature+rupture+of+membranes+%28PPROM%29%3F&rft.au=Ramsey%2C+P+S%3BHauth%2C+J+C&rft.aulast=Ramsey&rft.aufirst=P&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Gynecologic Investigation, 409 12th Street, SW, Washington, DC 20024, USA; phone: 202 863-2544; fax: 202 863-0739; URL: sgionline.org. Paper No. #705 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Effect of body-mass index on therapeutic response to bacterial vaginosis in pregnancy AN - 39617255; 3769099 AU - Mastrobattista, J M Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39617255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Effect+of+body-mass+index+on+therapeutic+response+to+bacterial+vaginosis+in+pregnancy&rft.au=Mastrobattista%2C+J+M&rft.aulast=Mastrobattista&rft.aufirst=J&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Gynecologic Investigation, 409 12th Street, SW, Washington, DC 20024, USA; phone: 202 863-2544; fax: 202 863-0739; URL: sgionline.org. Paper No. #371 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Role of Pds1 phosphorylation in the DNA damage induced checkpoint arrest AN - 39616234; 3767902 AU - Agarwal, R AU - Tang, Z AU - Yu, H AU - Cohen-fix, O Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39616234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Role+of+Pds1+phosphorylation+in+the+DNA+damage+induced+checkpoint+arrest&rft.au=Agarwal%2C+R%3BTang%2C+Z%3BYu%2C+H%3BCohen-fix%2C+O&rft.aulast=Agarwal&rft.aufirst=R&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society of Cell Biology, 8120 Woodmont Ave., Suite 750, Bethesda MD 20814, USA; phone: 301-347-9300; fax: 301-347-9310; email: ascbinfo@ascb.org; URL: www.ascb.org. Paper No. 1579 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Vasoactive intestinal peptide increases activity dependent neuroprotective protein expression in cerebral cortical cultures AN - 39612502; 3769334 AU - Vink, J AU - Brenneman, DE AU - Goodwin, K AU - Poggi, S AU - Gozes, I AU - Pinhasov, A AU - Spong, CY Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39612502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Vasoactive+intestinal+peptide+increases+activity+dependent+neuroprotective+protein+expression+in+cerebral+cortical+cultures&rft.au=Vink%2C+J%3BBrenneman%2C+DE%3BGoodwin%2C+K%3BPoggi%2C+S%3BGozes%2C+I%3BPinhasov%2C+A%3BSpong%2C+CY&rft.aulast=Vink&rft.aufirst=J&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Society for Gynecologic Investigation, 409 12th Street, SW, Washington, DC 20024, USA; phone: 202 863-2544; fax: 202 863-0739; URL: sgionline.org. Paper No. #606 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Benefits of CE-MS for quantitative proteomics measurements AN - 39597493; 3769752 AU - Issaq, HJ AU - Janini, G M AU - Conrads, T P AU - Veenstra, T D Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39597493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Benefits+of+CE-MS+for+quantitative+proteomics+measurements&rft.au=Issaq%2C+HJ%3BJanini%2C+G+M%3BConrads%2C+T+P%3BVeenstra%2C+T+D&rft.aulast=Issaq&rft.aufirst=HJ&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: California Separation Science Society, 156 South Spruce Avenue, Suite 214, South San Francisco, CA 94080-4556, USA; phone: 650-876-0792; fax: 650-876-0793; email: cstewart@casss.org. Paper No. L0807-M N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Smith-lemli-opitz syndrome and inborn errors of cholesterol synthesis AN - 39585797; 3759096 AU - Porter, F D Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39585797?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Smith-lemli-opitz+syndrome+and+inborn+errors+of+cholesterol+synthesis&rft.au=Porter%2C+F+D&rft.aulast=Porter&rft.aufirst=F&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American College of Medical Genetics, 9650 Rockville Pike, Bethesda, MD 20814, USA; phone: 301-634-7127; fax: 601-634-0677; email: acmg@faseb.org; URL: www.acmg.net N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Stem cells in development and disease AN - 39572670; 3767770 AU - McKay, R Y1 - 2003/06/06/ PY - 2003 DA - 2003 Jun 06 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39572670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Stem+cells+in+development+and+disease&rft.au=McKay%2C+R&rft.aulast=McKay&rft.aufirst=R&rft.date=2003-06-06&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society of Cell Biology, 8120 Woodmont Ave., Suite 750, Bethesda MD 20814, USA; phone: 301-347-9300; fax: 301-347-9310; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Monovalent cation dependence and preference of GHKL ATPases and kinases. AN - 73321285; 12782329 AB - The GHKL phosphotransferase superfamily, characterized by four sequence motifs that form the ATP-binding site, consists of the ATPase domains of type II DNA topoisomerases, Hsp90, and MutL, and bacterial and mitochondrial protein kinases. In addition to a magnesium ion, which is essential for catalysis, a potassium ion bound adjacent to the triphosphate moiety of ATP in a rat mitochondrial protein kinase, BCK (branched-chain alpha-ketoacid dehydrogenase kinase), has been shown to be indispensable for nucleotide binding and hydrolysis. Using X-ray crystallographic, biochemical, and genetic analyses, we find that the monovalent cation-binding site is conserved in MutL, but both Na(+) and K(+) support the MutL ATPase activity. When Ala100 of MutL is substituted by proline, mimicking the K(+)-binding environment in BCK, the mutant MutL protein becomes exclusively dependent on Na(+) for the ATPase activity. The coordination of this Na(+) ion is identical to that of the K(+) ion in BCK and involves four carbonyl oxygen atoms emanating from the hinges of the ATP lid and a non-bridging oxygen of the bound nucleotide. A similar monovalent cation-binding site is found in DNA gyrase with additional coordination by a serine side chain. The conserved and protein-specific monovalent cation-binding site is unique to the GHKL superfamily and probably essential for both ATPase and kinase activity. Dependence on different monovalent cations for catalysis may be exploited for future drug design specifically targeting each individual member of the GHKL superfamily. JF - FEBS letters AU - Hu, Xiaojian AU - Machius, Mischa AU - Yang, Wei AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/06/05/ PY - 2003 DA - 2003 Jun 05 SP - 268 EP - 273 VL - 544 IS - 1-3 SN - 0014-5793, 0014-5793 KW - Cations KW - 0 KW - Escherichia coli Proteins KW - HSP90 Heat-Shock Proteins KW - Ions KW - MutL protein, E coli KW - Salts KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Sodium KW - 9NEZ333N27 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - MutL Proteins KW - EC 3.6.1.3 KW - DNA Gyrase KW - EC 5.99.1.3 KW - Magnesium KW - I38ZP9992A KW - Potassium KW - RWP5GA015D KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Potassium -- chemistry KW - Animals KW - Protein Structure, Secondary KW - DNA Gyrase -- metabolism KW - Dose-Response Relationship, Drug KW - Models, Molecular KW - Oxygen -- metabolism KW - Protein Binding KW - Mutagenesis KW - Binding Sites KW - Rats KW - Amino Acid Motifs KW - Adenosine Triphosphate -- metabolism KW - HSP90 Heat-Shock Proteins -- metabolism KW - Crystallography, X-Ray KW - Salts -- pharmacology KW - Sodium -- chemistry KW - Protein Structure, Tertiary KW - Mutation KW - Magnesium -- chemistry KW - Escherichia coli Proteins -- metabolism KW - Adenosine Triphosphatases -- metabolism KW - Adenosine Triphosphatases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73321285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=Monovalent+cation+dependence+and+preference+of+GHKL+ATPases+and+kinases.&rft.au=Hu%2C+Xiaojian%3BMachius%2C+Mischa%3BYang%2C+Wei&rft.aulast=Hu&rft.aufirst=Xiaojian&rft.date=2003-06-05&rft.volume=544&rft.issue=1-3&rft.spage=268&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-07 N1 - Date created - 2003-06-03 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1NHJ; PDB; 1NHI; 1NHH N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of adolescent tobacco smokers: issues and opportunities for exposure reduction approaches. AN - 73286672; 12757960 AB - The cycle of tobacco dependence typically begins with the initiation of tobacco use during adolescence. Many teenagers try to quit smoking, fail and subsequently desire treatment for their tobacco dependence. Adolescents do not currently benefit from the same level of societal support for quit attempts as adults, and they may be less motivated for total cessation despite the short and long-term health consequences of smoking. Overall, the combination of low participation, high attrition and low complete cessation rates for adolescent smokers in treatment prompts the consideration of alternative treatment endpoints. It is likely that interactions among the processes of child and adolescent development, smoke exposure and trajectory influence patterns of tobacco use and treatment for tobacco dependence in adolescents. A rational framework is needed to integrate the study of these dynamic interactions to address tobacco dependence among youth from an exposure reduction, in addition to a cessation, perspective. This paper considers the issues and potential implications of tobacco exposure reduction therapy as an intermediate treatment goal for adolescent smokers who are dependent or dependence-prone, but for whom initial treatment interventions do not yield complete tobacco cessation. JF - Drug and alcohol dependence AU - Moolchan, Eric T AU - Aung, A Thiri AU - Henningfield, Jack E AD - Intramural Research Program, Clinical Pharmacology and Therapeutics Research Branch, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. emoolcha@intra.nida.nih.gov Y1 - 2003/06/05/ PY - 2003 DA - 2003 Jun 05 SP - 223 EP - 232 VL - 70 IS - 3 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Models, Psychological KW - Public Health KW - Humans KW - Smoking Cessation KW - Adolescent Behavior -- psychology KW - Marketing KW - Public Policy KW - Adolescent KW - Tobacco Use Disorder -- therapy KW - Tobacco Use Disorder -- prevention & control KW - Smoking -- psychology KW - Smoking -- prevention & control KW - Environmental Exposure -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73286672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Treatment+of+adolescent+tobacco+smokers%3A+issues+and+opportunities+for+exposure+reduction+approaches.&rft.au=Moolchan%2C+Eric+T%3BAung%2C+A+Thiri%3BHenningfield%2C+Jack+E&rft.aulast=Moolchan&rft.aufirst=Eric&rft.date=2003-06-05&rft.volume=70&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-04 N1 - Date created - 2003-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maternal fish consumption and infant birth size and gestation: New York State Angler Cohort Study. AN - 71610967; 12826023 AB - The scientific literature poses a perplexing dilemma for pregnant women with respect to the consumption of fish from natural bodies of water. On one hand, fish is a good source of protein, low in fat and a rich source of other nutrients all of which have presumably beneficial effects on developing embryos and fetuses. On the other hand, consumption of fish contaminated with environmental toxicants such as polychlorinated biphenyls (PCBs) has been associated with decrements in gestation and birth size. 2,716 infants born between 1986-1991 to participants of the New York State Angler Cohort Study were studied with respect to duration of maternal consumption of contaminated fish from Lake Ontario and its tributaries and gestation and birth size. Hospital delivery records (maternal and newborn) were obtained for 92% of infants for the ascertainment of gestation (weeks), birth size (weight, length, chest, and head circumference) and other known determinants of fetal growth (i.e., maternal parity, history of placental infarction, uterine bleeding, pregnancy loss or cigarette smoking and infant's race, sex and presence of birth defect). Duration of maternal fish consumption prior to the index infant's birth was categorized as: none; 1-2, 3-7, 8+ years, while birth weight (in grams), birth length (in centimeters), and head and chest circumference (in centimeters) were left as continuous variables in multiple linear regression models. Birth size percentiles, ponderal indices and head to chest circumference ratios were computed to further assess proportionality and birth size in relation to gestational age. Analysis of variance failed to identify significant mean differences in gestation or any measure of birth size in relation to duration of maternal lifetime fish consumption. Multiple linear regressions identified gestational age, male sex, number of daily cigarettes, parity and placental infarction, as significant determinants of birth size. The results support the absence of an adverse relation between Lake Ontario fish consumption and reduced birth size as measured by weight, length and head circumference. Biological determinants and maternal cigarette smoking during pregnancy remain important determinants of birth size. JF - Environmental health : a global access science source AU - Buck, Germaine M AU - Tee, Grace P AU - Fitzgerald, Edward F AU - Vena, John E AU - Weiner, John M AU - Swanson, Mya AU - Msall, Michael E AD - Epidemiology Branch Division of Epidemiology, Statistics & Prevention Research National Institute of Child Health & Human Development 6100 Executive Blvd, Room 7B03 Rockville, MD 20852, USA. gb156i@nih.gov Y1 - 2003/06/02/ PY - 2003 DA - 2003 Jun 02 SP - 7 VL - 2 IS - 1 KW - Water Pollutants, Chemical KW - 0 KW - Index Medicus KW - Life Style KW - Regression Analysis KW - New York KW - Fresh Water -- chemistry KW - Pregnancy Trimester, First KW - Humans KW - Cohort Studies KW - Infant, Newborn KW - Food Contamination KW - Fetal Development -- drug effects KW - Female KW - Pregnancy Outcome KW - Pregnancy KW - Maternal Exposure -- adverse effects KW - Birth Weight -- physiology KW - Water Pollutants, Chemical -- toxicity KW - Birth Weight -- drug effects KW - Maternal Nutritional Physiological Phenomena KW - Fish Products -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71610967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+%3A+a+global+access+science+source&rft.atitle=Maternal+fish+consumption+and+infant+birth+size+and+gestation%3A+New+York+State+Angler+Cohort+Study.&rft.au=Buck%2C+Germaine+M%3BTee%2C+Grace+P%3BFitzgerald%2C+Edward+F%3BVena%2C+John+E%3BWeiner%2C+John+M%3BSwanson%2C+Mya%3BMsall%2C+Michael+E&rft.aulast=Buck&rft.aufirst=Germaine&rft.date=2003-06-02&rft.volume=2&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Environmental+health+%3A+a+global+access+science+source&rft.issn=1476-069X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-23 N1 - Date created - 2004-11-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Clin Nutr. 2000 Jan;71(1 Suppl):179S-88S [10617969] Environ Res. 1999 Feb;80(2 Pt 2):S166-S174 [10092430] Chemosphere. 2000 May-Jun;40(9-11):1255-62 [10739070] Epidemiology. 2000 Jul;11(4):388-93 [10874544] Ann Epidemiol. 2001 Apr;11(3):186-93 [11248582] Obstet Gynecol Surv. 2001 May;56(5 Suppl 1):S1-13 [11333379] Int J Epidemiol. 2001 Dec;30(6):1272-8 [11821327] Int J Epidemiol. 2001 Dec;30(6):1279-80 [11821328] BMJ. 2002 Feb 23;324(7335):447 [11859044] Pediatrics. 1966 Mar;37(3):403-8 [5906365] HSMHA Health Rep. 1971 Dec;86(12):1083-91 [5157795] J Perinat Med. 1974;2(3):147-60 [4377575] J Pediatr. 1984 Aug;105(2):315-20 [6431068] J Am Diet Assoc. 1986 Jun;86(6):788-93 [3711560] J Pediatr. 1986 Aug;109(2):335-41 [3090217] Lancet. 1986 Aug 16;2(8503):367-9 [2874370] Arch Environ Contam Toxicol. 1987 Jul;16(4):455-60 [3111392] Science. 1988 Jul 15;241(4863):334-6 [3133768] Am J Epidemiol. 1989 Feb;129(2):395-406 [2492144] Lancet. 1989 May 20;1(8647):1146 [2566093] J Clin Epidemiol. 1989;42(12):1171-8 [2585008] Int J Epidemiol. 1990 Dec;19(4):971-7 [2084030] Environ Res. 1992 Oct;59(1):189-201 [1425509] Vital Health Stat 2. 1993 Mar;(116):1-19 [8328134] Epidemiol Rev. 1993;15(2):399-413 [8174664] Hum Exp Toxicol. 1994 Dec;13(12):900-6 [7718310] Arch Environ Contam Toxicol. 1995 May;28(4):431-5 [7755397] Early Hum Dev. 1996 Mar 22;44(3):161-7 [8654309] Toxicol Ind Health. 1996 May-Aug;12(3-4):327-34 [8843550] Scand J Work Environ Health. 1996 Aug;22(4):260-6 [8881014] Am J Public Health. 1997 Feb;87(2):301 [9103123] Arch Environ Contam Toxicol. 1997 Apr;32(3):329-36 [9096084] Br J Nutr. 1997 Jul;78 Suppl 1:S5-13 [9292771] Am J Epidemiol. 1997 Dec 1;146(11):955-60 [9400337] Am J Epidemiol. 1998 Mar 1;147(5):493-502 [9525537] Arch Environ Health. 1998 Mar-Apr;53(2):147-55 [9577938] Environ Health Perspect. 1998 May;106(5):279-89 [9560354] Pediatr Res. 1998 Oct;44(4):538-45 [9773843] BJOG. 2000 Mar;107(3):382-95 [10740336] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A cervical lymph node metastatic model of human tongue carcinoma: Serial and orthotopic transplantation of histologically intact patient specimens in nude mice. AN - 85378918; pmid-12796881 AB - A lymph node metastatic model of human tongue carcinoma using orthotopic and serial transplantation was established in nude mice to study the invasive and metastatic properties of human tongue cancer. Materials and Methods: Lymph node metastatic specimens of human tongue carcinoma were transplanted into nude mice orthotopically. Tumors dissected from the metastatic lymph nodes of the nude mice were serially transplanted into tongues of disease-free nude mice at 4-week intervals.All mice developed aggressive and diffuse well-differentiated squamous cell carcinoma at tongue recipient sites. Tumor cells invaded to lymphatic vessels. In addition, increased cervical lymph node metastasis was noted in the first (3 of 14, or 21%), second (4 of 11, or 36%), third (6 of 10, or 60%), or fourth (11 of 14, or 79%) transplantation. In mice, 2 of 14 lung metastases were found in the fourth round of transplantation.After surgical specimens of the lymph node metastasis for human tongue cancer were transplanted into the tongue of nude mice, the clinical characteristics of human tongue carcinoma, especially invasion and metastasis, were observed. This metastatic model involving orthotopic and serial transplantation should be useful for studies on the mechanisms, treatment, and prevention of human carcinoma of tongue.Copyright 2003 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 61:696-700, 2003 JF - Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons AU - Qiu, Cunping AU - Wu, Hong AU - He, Huajun AU - Qiu, Weiliu AD - Visiting Fellow, Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. cunping_qui@nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 696 EP - 700 VL - 61 IS - 6 SN - 0278-2391, 0278-2391 KW - National Library of Medicine KW - Animals KW - Carcinoma, Squamous Cell: pathology KW - *Carcinoma, Squamous Cell: secondary KW - *Disease Models, Animal KW - Female KW - Humans KW - *Lymph Nodes: pathology KW - Lymph Nodes: transplantation KW - *Lymphatic Metastasis KW - Male KW - Mice KW - Mice, Inbred BALB C KW - Mice, Nude KW - Middle Aged KW - Neck KW - Neoplasm Invasiveness KW - Neoplasm Transplantation KW - *Tongue Neoplasms: pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85378918?accountid=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+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.atitle=A+cervical+lymph+node+metastatic+model+of+human+tongue+carcinoma%3A+Serial+and+orthotopic+transplantation+of+histologically+intact+patient+specimens+in+nude+mice.&rft.au=Qiu%2C+Cunping%3BWu%2C+Hong%3BHe%2C+Huajun%3BQiu%2C+Weiliu&rft.aulast=Qiu&rft.aufirst=Cunping&rft.date=2003-06-01&rft.volume=61&rft.issue=6&rft.spage=696&rft.isbn=&rft.btitle=&rft.title=Journal+of+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.issn=02782391&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Central and autonomic nervous system integration in emotion. AN - 85374183; pmid-12812807 AB - Emotions involve physiological responses that are regulated by the brain. The present paper reviews the empirical literature on central nervous system (CNS) and autonomic nervous system (ANS) concomitants of emotional states, with a focus on studies that simultaneously assessed CNS and ANS activity. The reviewed data support two primary conclusions: (1) numerous cortical and subcortical regions show co-occurring activity with ANS responses in emotion, and (2) there may be reversed asymmetries on cortical and subcortical levels with respect to CNS/ANS interrelations. These observations are interpreted in terms of a model of neurovisceral integration in emotion, and directions for future research are presented. JF - Brain and cognition AU - Hagemann, Dirk AU - Waldstein, Shari R AU - Thayer, Julian F AD - Laboratory of Personality and Cognition, National Institute on Aging, National Institutes of Health, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. hagemann@uni-trier.de Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 79 EP - 87 VL - 52 IS - 1 SN - 0278-2626, 0278-2626 KW - Index Medicus KW - National Library of Medicine KW - *Affect: physiology KW - *Autonomic Nervous System: physiology KW - Brain: physiology KW - *Central Nervous System: physiology KW - Electroencephalography KW - Evoked Potentials: physiology KW - Functional Laterality: physiology KW - Heart Rate: physiology KW - Humans KW - Neural Inhibition: physiology KW - Visual Fields: physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85374183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+and+cognition&rft.atitle=Central+and+autonomic+nervous+system+integration+in+emotion.&rft.au=Hagemann%2C+Dirk%3BWaldstein%2C+Shari+R%3BThayer%2C+Julian+F&rft.aulast=Hagemann&rft.aufirst=Dirk&rft.date=2003-06-01&rft.volume=52&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=Brain+and+cognition&rft.issn=02782626&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - A new spontaneous mutation in the mouse Ames waltzer gene, Pcdh15. AN - 85366987; pmid-12782354 AB - A recessive deafness mutation in the mouse arose spontaneously and was identified in a colony segregating a null allele of the gastrin-releasing peptide receptor (Grpr) locus. Auditory-evoked brain stem response measurements revealed deafness in 7-week-old affected mice. By linkage analyses, the mutant phenotype was mapped near marker D10Mit186 and the protocadherin gene Pcdh15. As shown by complementation testing, the new mutation is allelic with Ames waltzer (Pcdh15(av)). Sequencing mutant-derived brain Pcdh15 cDNAs identified the insertion of a cytosine residue at nucleotide position c2099 (2099insC), which results in a frame-shift and premature stop codon. Abnormal stereocilia on inner and outer hair cells of the organ of Corti were identified by scanning electron microscopy as early as postnatal day 0 and cross-sectional histology revealed severe neuroepithelial degeneration in cochleas of 30-50-day-old mutants. The new allele of Ames waltzer, designated Pcdh15(av-Jfb), may aid in studying the histopathology associated with Usher syndrome type 1F, which is caused by a functional null allele of PCDH15. JF - Hearing research AU - Hampton, Lori L AU - Wright, Charles G AU - Alagramam, Kumar N AU - Battey, James F AU - Noben-Trauth, Konrad AD - G-Protein Coupled Receptors Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 67 EP - 75 VL - 180 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Auditory Threshold KW - Base Sequence: genetics KW - Behavior, Animal: physiology KW - *Cadherins: genetics KW - Cochlea: innervation KW - Cochlea: pathology KW - Cytosine KW - *Deafness: genetics KW - Deafness: pathology KW - Evoked Potentials, Auditory, Brain Stem KW - *Frameshift Mutation: genetics KW - Genes, Recessive KW - Genetic Complementation Test KW - Genetic Linkage KW - Mice KW - Mice, Inbred Strains KW - *Movement Disorders: genetics KW - Movement Disorders: pathology KW - Phenotype KW - *Protein Precursors: genetics KW - Spiral Ganglion: pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85366987?accountid=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=A+new+spontaneous+mutation+in+the+mouse+Ames+waltzer+gene%2C+Pcdh15.&rft.au=Hampton%2C+Lori+L%3BWright%2C+Charles+G%3BAlagramam%2C+Kumar+N%3BBattey%2C+James+F%3BNoben-Trauth%2C+Konrad&rft.aulast=Hampton&rft.aufirst=Lori&rft.date=2003-06-01&rft.volume=180&rft.issue=1-2&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Hearing+research&rft.issn=03785955&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Effects of boric acid supplementation on bone histomorphometry, metabolism, and biomechanical properties in aged female F-344 rats AN - 815541459; 13855873 AB - Postmenopausal women may benefit from dietary interventions in order to increase bone strength and prevent fractures. Dietary boron (B) may be beneficial for optimal calcium metabolism and, as a consequence, optimal bone metabolism. The present study evaluated the effects of boron, in the form of boric acid, with or without 17 beta -estradiol (E sub(2)) supplementation (via subcutaneous implant), in ovariectomized (OVX) aged 13-mo-old F-344 rats. Boric acid was administered by gavage at a subtoxic dose (8.7 mg B/kg/d) for 40 d. Results indicate that serum level of minerals as well as osteocalcin (a marker of bone resorption) are dependent to a greater extent on the hormonal status of the animals than on boron supplementation. Boron treatment increased the E sub(2)-induced elevation of urinary calcium and magnesium. Bone mineral density (BMD) of the L5 vertebra and proximal femur was highest in the E sub(2)-treated groups; no increase in BMD was conferred by boron treatment. By histomorphometry of the proximal tibial metaphysis, osteoblastic, osteoid, and eroded surfaces were significantly suppressed by E sub(2) treatment, but not by boron treatment. In biomechanical testing of femur and vertebra, neither E sub(2) nor boron treatment significantly increased bone strength. At the levels given, boron alone provided no protection against OVX-induced osteopenia. In addition, combination therapy (B + E sub(2)) provided no additional benefits over those of 17 beta -estradiol treatment alone in this aged rat model. JF - Biological Trace Element Research AU - Gallardo-Williams, Maria T AU - Maronpot, Robert R AU - Turner, Charles H AU - Johnson, Christopher S AU - Harris, Martha W AU - Jayo, Manuel J AU - Chapin, Robert E AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 155 EP - 169 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 93 IS - 1-3 SN - 0163-4984, 0163-4984 KW - Toxicology Abstracts; Calcium & Calcified Tissue Abstracts KW - Femur KW - Bone strength KW - Vertebrae KW - Osteopenia KW - Osteoblasts KW - Bone mineral density KW - Post-menopause KW - Calcium (urinary) KW - Bone resorption KW - 17 beta -Estradiol KW - boric acid KW - Mechanical properties KW - Osteoid KW - Osteocalcin KW - Fractures KW - Bone histomorphometry KW - Metaphysis KW - Boron KW - Serum levels KW - Calcium metabolism KW - Spine KW - Dietary supplements KW - Ovariectomy KW - Bone turnover KW - Magnesium KW - Menopause KW - X 24360:Metals KW - T 2020:Nutrition and Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/815541459?accountid=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=Biological+Trace+Element+Research&rft.atitle=Effects+of+boric+acid+supplementation+on+bone+histomorphometry%2C+metabolism%2C+and+biomechanical+properties+in+aged+female+F-344+rats&rft.au=Gallardo-Williams%2C+Maria+T%3BMaronpot%2C+Robert+R%3BTurner%2C+Charles+H%3BJohnson%2C+Christopher+S%3BHarris%2C+Martha+W%3BJayo%2C+Manuel+J%3BChapin%2C+Robert+E&rft.aulast=Gallardo-Williams&rft.aufirst=Maria&rft.date=2003-06-01&rft.volume=93&rft.issue=1-3&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Biological+Trace+Element+Research&rft.issn=01634984&rft_id=info:doi/10.1385%2FBTER%3A93%3A1-3%3A155 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Bone strength; Femur; Vertebrae; Osteopenia; Osteoblasts; Bone mineral density; Post-menopause; Calcium (urinary); 17 beta -Estradiol; Bone resorption; boric acid; Mechanical properties; Osteoid; Osteocalcin; Bone histomorphometry; Fractures; Metaphysis; Boron; Serum levels; Calcium metabolism; Spine; Dietary supplements; Bone turnover; Ovariectomy; Magnesium; Menopause DO - http://dx.doi.org/10.1385/BTER:93:1-3:155 ER - TY - CONF T1 - Role of iron in alcoholic liver disease: introduction and summary of the symposium. AN - 73717039; 12957291 AB - The National Institute on Alcohol Abuse and Alcoholism and the Office of Dietary Supplements, National Institutes of Health, sponsored a symposium on the "Role of Iron in Alcoholic Liver Disease" at Bethesda, Maryland, USA, October 2002. Alcoholic liver disease is a major cause of illness and death in the United States. Oxidative stress plays a key role in the pathogenesis of alcoholic liver disease. Iron can induce oxidative stress by catalyzing the conversion of superoxide and hydrogen peroxide to more potent oxidants such as hydroxyl radicals, which can cause tissue injury by initiating lipid peroxidation and causing oxidation of proteins and nucleic acids. Increasing evidence supports the suggestion that iron plays a significant role in the pathogenesis of alcoholic liver disease by exacerbating oxidative stress. Understanding the underlying mechanisms by which iron participates in the initiation and development of alcoholic liver disease may help design strategies for the treatment and prevention of the disease. For this symposium, nine speakers were invited to address the following issues: (1) iron intake from foods and dietary supplements; (2) hepatic iron overload in alcoholic liver disease; (3) iron-dependent activation of nuclear factor-kappa B (NF-kappaB) in Kupffer cells; (4) iron and cytochrome P450 2E1 (CYP2E1)-dependent oxidative stress and liver toxicity; (5) iron-induced oxidative stress in alcoholic hepatic fibrogenesis; (6) hemochromatosis and alcoholic liver disease; (7) iron as a co-morbid factor in nonhemochromatotic liver diseases; (8) iron and liver cancer; and (9) iron chelators and iron toxicity. On the basis of these presentations, it is concluded that heavy alcohol intake can result in increased accumulation of iron in the liver, in both hepatocytes and Kupffer cells. Iron-induced oxidative stress may promote the severity of alcoholic liver disease by (1) inducing NF-kappaB activation and subsequently increasing transcription of proinflammatory cytokines in Kupffer cells; (2) exacerbating CYP2E1-induced oxidative stress, especially in hepatocytes, through production of more toxic hydroxyl radicals; (3) stimulating hepatic stellate cells to produce excess amount of collagen and other matrix proteins that can lead to fibrosis; and (4) causing DNA damage and mutations that promote the development of liver cancer. Dietary iron supplements may further exacerbate the severity of alcoholic liver disease by increasing the magnitude of oxidative stress. We hope that the studies presented will stimulate further research in this exciting area. JF - Alcohol (Fayetteville, N.Y.) AU - Purohit, Vishnudutt AU - Russo, Denise AU - Salin, Marvin Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 93 EP - 97 VL - 30 IS - 2 KW - Iron Chelating Agents KW - 0 KW - Iron, Dietary KW - NF-kappa B KW - Iron KW - E1UOL152H7 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Index Medicus KW - United States KW - Humans KW - Liver -- metabolism KW - NF-kappa B -- physiology KW - Iron, Dietary -- administration & dosage KW - Liver Neoplasms KW - Oxidative Stress KW - National Institutes of Health (U.S.) KW - Hemochromatosis KW - Kupffer Cells -- metabolism KW - Cytochrome P-450 CYP2E1 -- physiology KW - Dietary Supplements KW - Iron Overload KW - Liver Diseases, Alcoholic KW - Iron -- physiology KW - Iron -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73717039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Role+of+iron+in+alcoholic+liver+disease%3A+introduction+and+summary+of+the+symposium.&rft.au=Purohit%2C+Vishnudutt%3BRusso%2C+Denise%3BSalin%2C+Marvin&rft.aulast=Purohit&rft.aufirst=Vishnudutt&rft.date=2003-06-01&rft.volume=30&rft.issue=2&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-29 N1 - Date created - 2003-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety and efficacy of nebulized zanamivir in hospitalized patients with serious influenza. AN - 73649298; 12924534 AB - Influenza is an important cause of hospitalization due to lower respiratory tract involvement for which there is no specific antiviral treatment with proven efficacy. We conducted a double-blind, randomized, placebo-controlled trial to assess the tolerability and efficacy of nebulized zanamivir (16 mg four times a day) in combination with rimantadine compared to rimantadine with nebulized saline for treating influenza in adults hospitalized with influenza. Twenty patients tolerated the inhaled zanamivir (ZNV) plus rimantadine without decline in peak expiratory flow rates compared to the 21 who received inhaled saline. The study was terminated early because the approval of ZNV made further enrollment untenable. No significant differences were observed in the proportion of patients shedding virus by treatment day 3 (57% ZNV plus rimantadine, 67% placebo plus rimantadine), or in the durations of hospitalization and supplemental oxygen use. More ZNV plus rimantadine recipients exhibited no or mild cough on day 3 of treatment (94 vs 55%, P=0.01). Two rimantadine-resistant viruses emerged during rimantadine monotherapy; no ZNV resistance was observed. Nebulized ZNV appears to be well tolerated in this hospitalized population but further studies are needed to assess its efficacy. JF - Antiviral therapy AU - Ison, Michael G AU - Gnann, John W AU - Nagy-Agren, Stephanie AU - Treannor, John AU - Paya, Carlos AU - Steigbigel, Roy AU - Elliott, Michael AU - Weiss, Heidi L AU - Hayden, Frederick G AU - NIAID Collaborative Antiviral Study Group AD - University of Virginia, Charlottesville, Va., USA. ; NIAID Collaborative Antiviral Study Group Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 183 EP - 190 VL - 8 IS - 3 SN - 1359-6535, 1359-6535 KW - Antiviral Agents KW - 0 KW - Guanidines KW - Pyrans KW - Sialic Acids KW - Rimantadine KW - 0T2EF4JQTU KW - Zanamivir KW - L6O3XI777I KW - Index Medicus KW - Double-Blind Method KW - Humans KW - Aged KW - Rimantadine -- therapeutic use KW - Drug Therapy, Combination KW - Drug Resistance, Viral KW - Aged, 80 and over KW - Nebulizers and Vaporizers KW - Respiratory Therapy -- methods KW - Adult KW - Rimantadine -- administration & dosage KW - Rimantadine -- adverse effects KW - Middle Aged KW - Female KW - Male KW - Sialic Acids -- therapeutic use KW - Sialic Acids -- adverse effects KW - Antiviral Agents -- therapeutic use KW - Antiviral Agents -- administration & dosage KW - Sialic Acids -- administration & dosage KW - Antiviral Agents -- adverse effects KW - Influenza, Human -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73649298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapy&rft.atitle=Safety+and+efficacy+of+nebulized+zanamivir+in+hospitalized+patients+with+serious+influenza.&rft.au=Ison%2C+Michael+G%3BGnann%2C+John+W%3BNagy-Agren%2C+Stephanie%3BTreannor%2C+John%3BPaya%2C+Carlos%3BSteigbigel%2C+Roy%3BElliott%2C+Michael%3BWeiss%2C+Heidi+L%3BHayden%2C+Frederick+G%3BNIAID+Collaborative+Antiviral+Study+Group&rft.aulast=Ison&rft.aufirst=Michael&rft.date=2003-06-01&rft.volume=8&rft.issue=3&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Antiviral+therapy&rft.issn=13596535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-05 N1 - Date created - 2003-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of neurosteroids on epileptiform activity induced by picrotoxin and 4-aminopyridine in the rat hippocampal slice. AN - 73619839; 12948618 AB - The neurosteroids allopregnanolone (5alpha-pregnan-3alpha-ol-20-one; 5alpha,3alpha-P) and its 5beta-epimer pregnanolone (5beta,3alpha-P), and pregnenolone sulfate (PS) were examined for effects on spontaneous epileptiform discharges induced by 100 microM picrotoxin (PTX) and 55 microM 4-aminopyridine (4-AP) in the CA3 region of the rat hippocampal slice. At a concentration of 10 microM, 5alpha,3alpha-P partially reduced PTX-induced bursting and at 30 and 90 microM completely suppressed bursting. In contrast, 100 microM 5beta,3alpha-P failed to alter the discharge frequency. 5alpha,3alpha-P depressed 4-AP-induced bursting with similar potency as in the PTX model; 100 microM 5beta,3alpha-P was also partially effective. In the 4-AP model, 5alpha,3alpha-P inhibited both the more frequent predominantly positive-going potentials as well as the less frequent negative-going potentials that may be generated by synchronous GABAergic interneuron firing. PS enhanced the PTX bursting frequency and, in the 4-AP model, increased the frequency of negative potentials but did not alter the frequency of positive potentials. By itself, PS did not induce bursting. The effects of the steroids in the in vitro seizure models largely correspond with their activities on GABA(A) receptors; suppression of discharges may occur as a result of direct activation of these receptors rather than modulation of GABA-mediated synaptic responses. PTX and 4-AP-induced bursting in the hippocampal slice are useful models for directly assessing neurosteroid effects on seizure susceptibility under conditions that eliminate the factor of brain bioavailability. JF - Epilepsy research AU - Salazar, Patricia AU - Tapia, Ricardo AU - Rogawski, Michael A AD - Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 49 Convent Drive Room 5A75 MSC 4457, Bethesda, MD 20892-4457, USA. PY - 2003 SP - 71 EP - 82 VL - 55 IS - 1-2 SN - 0920-1211, 0920-1211 KW - pregnenolone sulfate KW - 04Y4D91RG0 KW - Picrotoxin KW - 124-87-8 KW - Pregnenolone KW - 73R90F7MQ8 KW - 4-Aminopyridine KW - BH3B64OKL9 KW - Pregnanolone KW - BXO86P3XXW KW - Index Medicus KW - Rats KW - Animals KW - Action Potentials -- physiology KW - Epilepsy -- physiopathology KW - Epilepsy -- chemically induced KW - In Vitro Techniques KW - Action Potentials -- drug effects KW - Epilepsy -- drug therapy KW - Male KW - Pregnenolone -- pharmacology KW - Picrotoxin -- toxicity KW - Hippocampus -- physiology KW - 4-Aminopyridine -- toxicity KW - Pregnanolone -- therapeutic use KW - Pregnanolone -- pharmacology KW - Pregnenolone -- therapeutic use KW - Hippocampus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73619839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research&rft.atitle=Effects+of+neurosteroids+on+epileptiform+activity+induced+by+picrotoxin+and+4-aminopyridine+in+the+rat+hippocampal+slice.&rft.au=Salazar%2C+Patricia%3BTapia%2C+Ricardo%3BRogawski%2C+Michael+A&rft.aulast=Salazar&rft.aufirst=Patricia&rft.date=2003-06-01&rft.volume=55&rft.issue=1-2&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research&rft.issn=09201211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-23 N1 - Date created - 2003-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bayesian inference on order-constrained parameters in generalized linear models. AN - 73593343; 12926713 AB - In biomedical studies, there is often interest in assessing the association between one or more ordered categorical predictors and an outcome variable, adjusting for covariates. For a k-level predictor, one typically uses either a k-1 degree of freedom (df) test or a single df trend test, which requires scores for the different levels of the predictor. In the absence of knowledge of a parametric form for the response function, one can incorporate monotonicity constraints to improve the efficiency of tests of association. This article proposes a general Bayesian approach for inference on order-constrained parameters in generalized linear models. Instead of choosing a prior distribution with support on the constrained space, which can result in major computational difficulties, we propose to map draws from an unconstrained posterior density using an isotonic regression transformation. This approach allows flat regions over which increases in the level of a predictor have no effect. Bayes factors for assessing ordered trends can be computed based on the output from a Gibbs sampling algorithm. Results from a simulation study are presented and the approach is applied to data from a time-to-pregnancy study. JF - Biometrics AU - Dunson, David B AU - Neelon, Brian AD - Biostatistics Branch, National Institute of Environmental Health Sciences, MD A3-03, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA. dunson1@niehs.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 286 EP - 295 VL - 59 IS - 2 SN - 0006-341X, 0006-341X KW - Nitrous Oxide KW - K50XQU1029 KW - Index Medicus KW - Occupational Exposure KW - Nitrous Oxide -- adverse effects KW - Fertilization KW - Humans KW - Adult KW - Smoking -- adverse effects KW - Female KW - Pregnancy KW - Regression Analysis KW - Linear Models KW - Bayes Theorem UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73593343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Bayesian+inference+on+order-constrained+parameters+in+generalized+linear+models.&rft.au=Dunson%2C+David+B%3BNeelon%2C+Brian&rft.aulast=Dunson&rft.aufirst=David&rft.date=2003-06-01&rft.volume=59&rft.issue=2&rft.spage=286&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-16 N1 - Date created - 2003-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bayesian latent variable models for median regression on multiple outcomes. AN - 73584422; 12926714 AB - Often a response of interest cannot be measured directly and it is necessary to rely on multiple surrogates, which can be assumed to be conditionally independent given the latent response and observed covariates. Latent response models typically assume that residual densities are Gaussian. This article proposes a Bayesian median regression modeling approach, which avoids parametric assumptions about residual densities by relying on an approximation based on quantiles. To accommodate within-subject dependency, the quantile response categories of the surrogate outcomes are related to underlying normal variables, which depend on a latent normal response. This underlying Gaussian covariance structure simplifies interpretation and model fitting, without restricting the marginal densities of the surrogate outcomes. A Markov chain Monte Carlo algorithm is proposed for posterior computation, and the methods are applied to single-cell electrophoresis (comet assay) data from a genetic toxicology study. JF - Biometrics AU - Dunson, David B AU - Watson, M AU - Taylor, Jack A AD - Biostatistics Branch, MD A3-03, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA. dunson1@niehs.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 296 EP - 304 VL - 59 IS - 2 SN - 0006-341X, 0006-341X KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Regression Analysis KW - Mutagenicity Tests -- methods KW - Hydrogen Peroxide -- pharmacology KW - Normal Distribution KW - DNA Fragmentation -- drug effects KW - Markov Chains KW - Monte Carlo Method KW - Comet Assay -- methods KW - Multivariate Analysis KW - Bayes Theorem KW - Algorithms KW - Models, Statistical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73584422?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Bayesian+latent+variable+models+for+median+regression+on+multiple+outcomes.&rft.au=Dunson%2C+David+B%3BWatson%2C+M%3BTaylor%2C+Jack+A&rft.aulast=Dunson&rft.aufirst=David&rft.date=2003-06-01&rft.volume=59&rft.issue=2&rft.spage=296&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-16 N1 - Date created - 2003-08-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - How can we improve the assessment of safety in child and adolescent psychopharmacology? AN - 73561313; 12921470 AB - To identify approaches to improving methods for assessing tolerability and safety of psychotropic medications in children and adolescents. Strengths and limitations of current methodology were reviewed and possible alternatives examined. Research on the validity of safety evaluation has been extremely limited. No evidence-based "gold standard" exists. Clinical trials remain the best design to establish causality, but sample size limitations prevent the detection of infrequent, though serious, adverse events. Other designs, such as cohort and case-control studies, and approaches, such as mining of large databases, must be considered. The current lack of methodological standardization across studies prevents generalizations and meta-analyses. Because the issues relevant to drug safety are diverse, a variety of methodological approaches and instruments are needed. It is, however, possible to adopt standard basic definitions of adverse events, degree of severity, ascertainment methods, and recording procedures, as a common "core," to which more specific assessment instruments can be added. Systematic empirical testing and validation of safety methodology is needed. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Vitiello, Benedetto AU - Riddle, Mark A AU - Greenhill, Laurence L AU - March, John S AU - Levine, Jerome AU - Schachar, Russell J AU - Abikoff, Howard AU - Zito, Julie M AU - McCracken, James T AU - Walkup, John T AU - Findling, Robert L AU - Robinson, James AU - Cooper, Thomas B AU - Davies, Mark AU - Varipatis, Elena AU - Labellarte, Michael J AU - Scahill, Lawrence AU - Capasso, Lisa AD - Division of Services and Intervention Research, NIMH, Bethesda, MD 20982-9633, USA. bvitiell@nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 634 EP - 641 VL - 42 IS - 6 SN - 0890-8567, 0890-8567 KW - Psychotropic Drugs KW - 0 KW - Index Medicus KW - Humans KW - Child KW - Psychotropic Drugs -- adverse effects KW - Adolescent KW - Randomized Controlled Trials as Topic -- adverse effects KW - Male KW - Female KW - Child, Preschool KW - Psychopharmacology KW - Adverse Drug Reaction Reporting Systems -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73561313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=How+can+we+improve+the+assessment+of+safety+in+child+and+adolescent+psychopharmacology%3F&rft.au=Vitiello%2C+Benedetto%3BRiddle%2C+Mark+A%3BGreenhill%2C+Laurence+L%3BMarch%2C+John+S%3BLevine%2C+Jerome%3BSchachar%2C+Russell+J%3BAbikoff%2C+Howard%3BZito%2C+Julie+M%3BMcCracken%2C+James+T%3BWalkup%2C+John+T%3BFindling%2C+Robert+L%3BRobinson%2C+James%3BCooper%2C+Thomas+B%3BDavies%2C+Mark%3BVaripatis%2C+Elena%3BLabellarte%2C+Michael+J%3BScahill%2C+Lawrence%3BCapasso%2C+Lisa&rft.aulast=Vitiello&rft.aufirst=Benedetto&rft.date=2003-06-01&rft.volume=42&rft.issue=6&rft.spage=634&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-19 N1 - Date created - 2003-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tea can protect against aberrant crypt foci formation during azoxymethane induced rat colon carcinogenesis. AN - 73469389; 12866568 AB - Tea shows many health promoting activities including chemopreventive action during carcinogenesis due to the presence of antioxidative polyphenolic constituents. The present experiment evaluated the anticarcinogenic role of black tea infusion on azoxymethane induced colonic preneoplastic lesions, the aberrant crypt foci in Sprague-Dawley rats. Rats were injected with azoxymethane (15 mg/kg b.w.) and received oral administration of 1% and 2% (w/v) tea infusions from first day of carcinogen application. This treatment was continued for twelve weeks and assessed for aberrant crypt foci and compared with untreated carcinogen control group. Levels of lipid peroxidation were determined in liver as well as in colon tissue. During initiation phase of carcinogenesis, glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities were also evaluated. Significant reduction in the number of aberrant crypt foci and levels of lipid peroxidation among the tea-treated groups were observed. Induction of GST and GPx activities was noted during the initiation phase of carcinogenesis. Results of the present study indicate that the protective effect of black tea infusions may be due to an outcome of antioxidative influence of tea components on azoxymethane induced carcinogenesis. JF - Journal of experimental & clinical cancer research : CR AU - Sengupta, A AU - Ghosh, S AU - Das, S AD - Dept. of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata, India. archana_sen@yahoo.com Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 185 EP - 191 VL - 22 IS - 2 SN - 0392-9078, 0392-9078 KW - Antioxidants KW - 0 KW - Carcinogens KW - Flavonoids KW - Phenols KW - Polyphenols KW - Tea KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Azoxymethane KW - MO0N1J0SEN KW - Index Medicus KW - Administration, Oral KW - Animals KW - Phenols -- pharmacology KW - Glutathione Transferase -- metabolism KW - Biological Assay KW - Lipid Peroxidation KW - Neoplasms, Experimental KW - Rats KW - Rats, Sprague-Dawley KW - Antioxidants -- metabolism KW - Glutathione Peroxidase -- metabolism KW - Antioxidants -- pharmacology KW - Flavonoids -- pharmacology KW - Time Factors KW - Male KW - Precancerous Conditions -- prevention & control KW - Colonic Neoplasms -- drug therapy KW - Colonic Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73469389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Tea+can+protect+against+aberrant+crypt+foci+formation+during+azoxymethane+induced+rat+colon+carcinogenesis.&rft.au=Sengupta%2C+A%3BGhosh%2C+S%3BDas%2C+S&rft.aulast=Sengupta&rft.aufirst=A&rft.date=2003-06-01&rft.volume=22&rft.issue=2&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-10 N1 - Date created - 2003-07-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hodgkin's disease in HIV. AN - 73462290; 12852658 AB - The outcome of patients with HIV-HD has improved with better, combined antineoplastic and antiretroviral approaches. New and effective antiretroviral drugs (ie, protease inhibitors), in conjunction with nucleoside analogs, improve the control of the underlying HIV infection when used during treatment of HD with chemotherapy. In fact, the possibility of reducing viral load to undetectable levels and increasing the CD4+ cell count reduces the risk of OIs during antineoplastic treatment. The inclusion of hematopoietic growth factors in the treatment of patients with HIV-HD may allow for the administration of higher dose-intensity chemotherapy and the prolonged use of antiretroviral drugs, with the aim of improving the survival. Finally, more effective antineoplastic regimens--such as high-dose chemotherapy with autologous stem cell transplantation (which is required in the case of HIV-HD, due to its aggressiveness)--should be considered to improve the response rate and disease-free survival of these patients. JF - Hematology/oncology clinics of North America AU - Spina, Michele AU - Berretta, Massimiliano AU - Tirelli, Umberto AD - Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occ.le 12, 33081 Aviano (PN), Italy. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 843 EP - 858 VL - 17 IS - 3 SN - 0889-8588, 0889-8588 KW - Index Medicus KW - Humans KW - Treatment Outcome KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity KW - Lymphoma, AIDS-Related -- epidemiology KW - Lymphoma, AIDS-Related -- pathology KW - Hodgkin Disease -- drug therapy KW - Lymphoma, AIDS-Related -- drug therapy KW - Hodgkin Disease -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73462290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hodgkin%27s+disease+in+HIV.&rft.au=Spina%2C+Michele%3BBerretta%2C+Massimiliano%3BTirelli%2C+Umberto&rft.aulast=Spina&rft.aufirst=Michele&rft.date=2003-06-01&rft.volume=17&rft.issue=3&rft.spage=843&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 - 2004-01-14 N1 - Date created - 2003-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deletion of the Hsp70 chaperone gene SSB causes hypersensitivity to guanidine toxicity and curing of the [PSI+] prion by increasing guanidine uptake in yeast. AN - 73430008; 12684878 AB - Yeast Ssb proteins (Ssbp) are ribosome-associated Hsp70 chaperones that function in translation. Elevated levels of Ssbp enhance the ability of over-expressed Hsp104 chaperone to eliminate the yeast [PSI+] prion, while depletion of Ssbp reduces this effect. Millimolar concentrations of guanidine in the growth medium cure yeast cells of prions by inactivating Hsp104. Guanidine is also toxic to yeast, irrespective of the status of Hsp104 and [PSI+]. Strains that lack Ssbp are hypersensitive to guanidine toxicity. Here we show that ssb- cells have normal numbers of [PSI+] "seeds", but can be cured of [PSI+] using one-sixth of the guanidine concentration required to eliminate [PSI+] from SSB cells. Correspondingly, the level of intracellular guanidine was eight-fold higher in ssb- cells than in wild-type cells, which explains all effects of Ssbp depletion on susceptibility to guanidine. The sensitivity of wild-type cells to the effects of guanidine also correlated with guanidine uptake, which was enhanced at low temperature. Guanidine sensitivity of strains mutated in any of 16 ABC membrane transporters, which are implicated in multidrug resistance, was normal. We found that an erg6 mutant that has an altered membrane lipid composition was hypersensitive to guanidine toxicity, but the lipid composition of ssb- cells was identical to that of wild-type cells. Our results suggest that Ssbp depletion does not affect prion seed regeneration, and that elevated guanidine uptake by ssb- cells may be due to increased retention rather than to an alteration in active or passive transport of the compound. JF - Molecular genetics and genomics : MGG AU - Jones, G W AU - Song, Y AU - Masison, D C AD - Laboratory of Biochemistry and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, Rm 407, MSC 0851, MD 20892-0851, Bethesda, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 304 EP - 311 VL - 269 IS - 3 SN - 1617-4615, 1617-4615 KW - Fungal Proteins KW - 0 KW - HSP70 Heat-Shock Proteins KW - Peptide Termination Factors KW - Prions KW - RNA, Messenger KW - SUP35 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Methyltransferases KW - EC 2.1.1.- KW - delta 24-sterol methyltransferase KW - EC 2.1.1.41 KW - Guanidine KW - JU58VJ6Y3B KW - Index Medicus KW - Methyltransferases -- genetics KW - RNA, Messenger -- metabolism KW - Cell Division -- physiology KW - Methyltransferases -- metabolism KW - HSP70 Heat-Shock Proteins -- genetics KW - Guanidine -- metabolism KW - Fungal Proteins -- metabolism KW - Yeasts -- genetics KW - HSP70 Heat-Shock Proteins -- deficiency KW - Guanidine -- toxicity KW - Yeasts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73430008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+genetics+and+genomics+%3A+MGG&rft.atitle=Deletion+of+the+Hsp70+chaperone+gene+SSB+causes+hypersensitivity+to+guanidine+toxicity+and+curing+of+the+%5BPSI%2B%5D+prion+by+increasing+guanidine+uptake+in+yeast.&rft.au=Jones%2C+G+W%3BSong%2C+Y%3BMasison%2C+D+C&rft.aulast=Jones&rft.aufirst=G&rft.date=2003-06-01&rft.volume=269&rft.issue=3&rft.spage=304&rft.isbn=&rft.btitle=&rft.title=Molecular+genetics+and+genomics+%3A+MGG&rft.issn=16174615&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-27 N1 - Date created - 2003-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of HIV-1 replication by the combined action of anti-gp41 single chain antibody and IL-16. AN - 73419014; 12834863 AB - HIV-1 replication is inhibited in T cells transfected with an anti-gp41 single chain antibody (ScFv) or IL-16. These two molecules target totally different events in the HIV-1 replication cycle. The present study shows that HIV-1 replication is inhibited to a substantially greater extent and for a longer duration in cells transfected with both anti-gp41 and IL-16 than with either molecule alone. It is concluded that anti-gp41 and IL-16 act in a synergistic fashion to inhibit HIV-1 replication. JF - Antiviral research AU - Devadas, Krishnakumar AU - Zhou, Paul AU - Tewari, Deepanker AU - Notkins, Abner Louis AD - Experimental Medicine Section, Oral Immunity and Infection Branch, Building 30, Room 121, NIDCR, National Institutes of Health, 30 Convent Drive, MSC 4322, Bethesda, MD 20892-4322, USA. devadas@cber.fda.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 67 EP - 70 VL - 59 IS - 1 SN - 0166-3542, 0166-3542 KW - Antibodies, Viral KW - 0 KW - Antigens, CD4 KW - HIV Envelope Protein gp41 KW - Interleukin-16 KW - Index Medicus KW - Spectrometry, Fluorescence KW - Electroporation KW - Transfection KW - Kinetics KW - Humans KW - Jurkat Cells KW - Cell Division -- drug effects KW - Antigens, CD4 -- biosynthesis KW - Drug Synergism KW - T-Lymphocytes -- virology KW - Virus Replication -- drug effects KW - Antibodies, Viral -- pharmacology KW - Interleukin-16 -- pharmacology KW - HIV Envelope Protein gp41 -- immunology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73419014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+HIV-1+replication+by+the+combined+action+of+anti-gp41+single+chain+antibody+and+IL-16.&rft.au=Devadas%2C+Krishnakumar%3BZhou%2C+Paul%3BTewari%2C+Deepanker%3BNotkins%2C+Abner+Louis&rft.aulast=Devadas&rft.aufirst=Krishnakumar&rft.date=2003-06-01&rft.volume=59&rft.issue=1&rft.spage=67&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 - 2003-10-23 N1 - Date created - 2003-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - P2Y6 nucleotide receptor activates PKC to protect 1321N1 astrocytoma cells against tumor necrosis factor-induced apoptosis. AN - 73414464; 12825835 AB - 1. We recently reported that the activation by UDP of rat P2Y6 nucleotide receptors expressed in 1321N1 astrocytoma cells protected them from TNFalpha-induced apoptosis by suppressing activation of caspase 3 and 8. This study aims to characterize the involvement of intracellular signaling pathways, including kinases involved in the antiapoptotic effect of UDP. 2. Cell death was induced in 1321N1 astrocytoma cells permanently expressing the rat P2Y6 receptor by exposure to TNFalpha in the presence of cycloheximide. The apoptotic fraction was analyzed using flow cytometry. 3. The activation of P2Y6 receptors by UDP both protected the astrocytes from TNF-alpha induced apoptosis and activated protein kinase C (PKC) isotypes. The phorbol ester PMA also activated PKC and protected the cells from TNFalpha-induced cell death. The alpha- and epsilon-isotypes of PKC were both activated in a persistent fashion upon 5-min exposure to either UDP (10 microM) or the phorbol ester PMA (100 nM). The PKCzeta isotype was markedly activated upon UDP treatment. 4. The addition of PKC inhibitors, GF109203X or Gö6976, partially antagonized the protective effect of UDP and reduced the UDP-induced phosphorylation of extracellular signal-regulated protein kinases (Erk). The inhibitors of Erk, PD98,059 or U0126, antagonized UDP-induced protection. 5. The antiapoptotic protein, Akt, was not affected by P2Y6 receptor activation. Incubation of the astrocytes with calcium modifiers BAPTA-AM or dantrolene, did not affect the UDP-induced protection from apoptosis. 6. The addition of phospholipase C (PLC) inhibitors, D609 or U73122, partially antagonized both UDP-induced protection and PKC activation. JF - Cellular and molecular neurobiology AU - Kim, Seong G AU - Gao, Zhan-Guo AU - Soltysiak, Kelly A AU - Chang, Tong-Shin AU - Brodie, Chaya AU - Jacobson, Kenneth A AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 401 EP - 418 VL - 23 IS - 3 SN - 0272-4340, 0272-4340 KW - Enzyme Inhibitors KW - 0 KW - Protein Isoforms KW - Proto-Oncogene Proteins KW - Receptors, Purinergic P2 KW - Tumor Necrosis Factor-alpha KW - purinoceptor P2Y6 KW - Uridine Diphosphate KW - 58-98-0 KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Akt1 protein, rat KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Protein Kinase C KW - EC 2.7.11.13 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Type C Phospholipases -- antagonists & inhibitors KW - Astrocytoma KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Protein Isoforms -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Uridine Diphosphate -- pharmacology KW - Uridine Diphosphate -- metabolism KW - Drug Interactions -- physiology KW - Type C Phospholipases -- metabolism KW - Rats KW - Calcium Signaling -- drug effects KW - Mitogen-Activated Protein Kinases -- drug effects KW - Tumor Cells, Cultured KW - Proto-Oncogene Proteins -- drug effects KW - Calcium Signaling -- physiology KW - Protein Isoforms -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- drug effects KW - Receptors, Purinergic P2 -- drug effects KW - Cell Membrane -- drug effects KW - Receptors, Purinergic P2 -- metabolism KW - Astrocytes -- drug effects KW - Apoptosis -- physiology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Apoptosis -- drug effects KW - Cell Membrane -- metabolism KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73414464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+neurobiology&rft.atitle=P2Y6+nucleotide+receptor+activates+PKC+to+protect+1321N1+astrocytoma+cells+against+tumor+necrosis+factor-induced+apoptosis.&rft.au=Kim%2C+Seong+G%3BGao%2C+Zhan-Guo%3BSoltysiak%2C+Kelly+A%3BChang%2C+Tong-Shin%3BBrodie%2C+Chaya%3BJacobson%2C+Kenneth+A&rft.aulast=Kim&rft.aufirst=Seong&rft.date=2003-06-01&rft.volume=23&rft.issue=3&rft.spage=401&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+neurobiology&rft.issn=02724340&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-13 N1 - Date created - 2003-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Physiol Gastrointest Liver Physiol. 2001 Dec;281(6):G1357-68 [11705740] Nature. 2001 Nov 15;414(6861):265-6 [11713514] Nature. 2001 Nov 15;414(6861):308-13 [11713530] Nature. 2001 Nov 15;414(6861):313-7 [11713531] Cell Biol Int. 2001;25(12):1213-9 [11748914] Am J Physiol Heart Circ Physiol. 2002 Feb;282(2):H784-92 [11788430] Cancer Res. 2002 Jan 15;62(2):488-96 [11809700] Biochem Pharmacol. 2003 Mar 15;65(6):923-31 [12623123] J Biol Chem. 1991 Aug 25;266(24):15771-81 [1874734] J Leukoc Biol. 1993 Jan;53(1):37-44 [8426090] J Biol Chem. 1993 May 5;268(13):9194-7 [8486620] Blood. 1995 Sep 15;86(6):2248-56 [7662972] J Biol Chem. 1995 Nov 3;270(44):26152-8 [7592819] Science. 1995 Nov 24;270(5240):1326-31 [7481820] Biochem Biophys Res Commun. 1996 May 15;222(2):303-8 [8670200] Trends Neurosci. 1996 Jan;19(1):13-8 [8787135] J Biol Chem. 1996 Jun 14;271(24):14560-6 [8662985] Mol Pharmacol. 1996 Aug;50(2):224-9 [8700127] Ciba Found Symp. 1996;198:130-9; discussion 139-41 [8879822] Neuroscience. 1996 Oct;74(4):1187-96 [8895885] Mol Biol Cell. 1996 Nov;7(11):1679-90 [8930892] Science. 1997 Jan 31;275(5300):661-5 [9005851] Neuroreport. 1996 Nov 25;7(18):2893-6 [9116204] Mol Cell Biol. 1997 Mar;17(3):1595-606 [9032287] Br J Pharmacol. 1997 Mar;120(5):807-12 [9138685] Trends Biochem Sci. 1997 Sep;22(9):355-8 [9301337] Biochim Biophys Acta. 1997 Oct 24;1333(2):F85-104 [9395283] Curr Opin Cell Biol. 1998 Apr;10(2):205-19 [9561845] J Biol Chem. 1998 Jun 5;273(23):14560-5 [9603971] J Biol Chem. 1998 Jul 24;273(30):19080-5 [9668091] Eur J Biochem. 1998 Jun 15;254(3):439-59 [9688254] Br J Pharmacol. 1998 Jun;124(4):703-10 [9690862] Biochem Biophys Res Commun. 1998 Jul 30;248(3):864-70 [9704019] Mol Carcinog. 1999 May;25(1):14-20 [10331740] J Neurosci. 1999 Jun 1;19(11):4211-20 [10341225] J Biol Chem. 1999 Jul 9;274(28):19545-50 [10391887] J Biol Chem. 1999 Aug 13;274(33):23526-34 [10438532] Cardiovasc Res. 1999 Jun;42(3):805-13 [10533621] Circulation. 1999 Nov 16;100(20):2100-7 [10562267] Br J Pharmacol. 2000 Mar;129(5):927-36 [10696092] Br J Pharmacol. 2000 Apr;129(7):1481-9 [10742305] J Biol Chem. 2000 May 5;275(18):13243-9 [10788429] Br J Pharmacol. 2000 Sep;131(1):51-6 [10960068] Ann Rheum Dis. 2000 Nov;59 Suppl 1:i6-16 [11053079] Cell Signal. 2000 Oct;12(9-10):659-65 [11080618] J Biol Chem. 2000 Dec 15;275(50):39767-72 [10995776] J Biol Chem. 2000 Dec 22;275(51):40620-7 [11016947] Mol Pharmacol. 2001 Jan;59(1):76-82 [11125027] Mol Cell Biol Res Commun. 2000 Aug;4(2):106-10 [11170840] J Cell Physiol. 2001 May;187(2):166-75 [11267996] J Cell Physiol. 2001 May;187(2):196-208 [11267999] J Biol Chem. 2001 May 11;276(19):16379-90 [11278310] J Biol Chem. 2001 May 11;276(19):16484-90 [11278665] Endocrinology. 2001 Jul;142(7):3014-26 [11416023] Biochem Biophys Res Commun. 2001 Jul 20;285(3):675-9 [11453646] Glia. 2001 Aug;35(2):111-20 [11460267] Oncogene. 2001 Jul 19;20(32):4365-72 [11466617] Am J Physiol Cell Physiol. 2001 Dec;281(6):C2010-9 [11698260] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Morbidity in 258 bipolar outpatients followed for 1 year with daily prospective ratings on the NIMH life chart method. AN - 73414248; 12823083 AB - A number of recent longitudinal outcome studies have found substantial long-term morbidity in patients with bipolar disorder. The detailed course and pattern of illness emerging despite comprehensive treatment with mood stabilizers and adjunctive agents have previously not been well delineated. 258 consecutive outpatients admitted from 1996 to 1999 to the Stanley Foundation Bipolar Network who had a full year of prospective daily clinician ratings on the National Institute of Mental Health-Life Chart Method were included in the analysis. Patients were diagnosed by the Structured Clinical Interview for DSM-IV, with the majority (76%) having bipolar I disorder. They completed a questionnaire on demographics and prior illness course, and variables associated with outcome were examined in a hierarchical multinomial logistic regression analysis. Patients were treated naturalistically with a mean of 4.1 psychotropic medications during the year. Despite comprehensive pharmacologic treatment, mean time depressed (33.2% of the year) was 3-fold higher than time manic (10.8%); 62.8% of patients had 4 or more mood episodes per year. Two thirds of the patients were substantially impacted by their illness; 26.4% were ill for more than three fourths of the year, and 40.7% were intermittently ill with major affective episodes. After logistic regression analysis, those who were ill most of the year, compared with the largely well group, had a significantly greater family history of substance abuse, 10 or more depressive episodes, and limited occupational functioning prior to Network entry. A majority of outpatients with bipolar illness, even with intense monitoring and treatment in specialty clinics, have a considerable degree of residual illness-related morbidity, including a 3-fold greater amount of time spent depressed versus time spent manic. A personal or family history of substance abuse, 10 or more prior depressions, and limited occupational functioning predicted the poorest outcomes. Additional interventions, particularly those targeted at treating depressive phases of bipolar illness, are greatly needed. JF - The Journal of clinical psychiatry AU - Post, Robert M AU - Denicoff, Kirk D AU - Leverich, Gabriele S AU - Altshuler, Lori L AU - Frye, Mark A AU - Suppes, Trisha M AU - Rush, A John AU - Keck, Paul E AU - McElroy, Susan L AU - Luckenbaugh, David A AU - Pollio, Chad AU - Kupka, Ralph AU - Nolen, Willem A AD - Stanley Foundation Bipolar Network and Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-12723, USA. robert.post@nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 680 EP - 90; quiz 738-9 VL - 64 IS - 6 SN - 0160-6689, 0160-6689 KW - Psychotropic Drugs KW - 0 KW - Index Medicus KW - Regression Analysis KW - Depressive Disorder -- psychology KW - Social Adjustment KW - Humans KW - Employment KW - Recurrence KW - Sickness Impact Profile KW - Prospective Studies KW - Risk Factors KW - Adult KW - Treatment Outcome KW - Depressive Disorder -- diagnosis KW - Depressive Disorder -- drug therapy KW - Family KW - Middle Aged KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Female KW - Male KW - Substance-Related Disorders -- epidemiology KW - Bipolar Disorder -- diagnosis KW - Ambulatory Care -- statistics & numerical data KW - Bipolar Disorder -- drug therapy KW - Psychotropic Drugs -- therapeutic use KW - Bipolar Disorder -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73414248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+psychiatry&rft.atitle=Morbidity+in+258+bipolar+outpatients+followed+for+1+year+with+daily+prospective+ratings+on+the+NIMH+life+chart+method.&rft.au=Post%2C+Robert+M%3BDenicoff%2C+Kirk+D%3BLeverich%2C+Gabriele+S%3BAltshuler%2C+Lori+L%3BFrye%2C+Mark+A%3BSuppes%2C+Trisha+M%3BRush%2C+A+John%3BKeck%2C+Paul+E%3BMcElroy%2C+Susan+L%3BLuckenbaugh%2C+David+A%3BPollio%2C+Chad%3BKupka%2C+Ralph%3BNolen%2C+Willem+A&rft.aulast=Post&rft.aufirst=Robert&rft.date=2003-06-01&rft.volume=64&rft.issue=6&rft.spage=680&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+psychiatry&rft.issn=01606689&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-25 N1 - Date created - 2003-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parkinson's disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation. AN - 73407658; 12826478 AB - Idiopathic Parkinson's disease (PD) is a devastating movement disorder characterized by selective degeneration of the nigrostriatal dopaminergic pathway. Neurodegeneration usually starts in the fifth decade of life and progresses over 5-10 years before reaching the fully symptomatic disease state. Despite decades of intense research, the etiology of sporadic PD and the mechanism underlying the selective neuronal loss remain unknown. However, the late onset and slow-progressing nature of the disease has prompted the consideration of environmental exposure to agrochemicals, including pesticides, as a risk factor. Moreover, increasing evidence suggests that early-life occurrence of inflammation in the brain, as a consequence of either brain injury or exposure to infectious agents, may play a role in the pathogenesis of PD. Most important, there may be a self-propelling cycle of inflammatory process involving brain immune cells (microglia and astrocytes) that drives the slow yet progressive neurodegenerative process. Deciphering the molecular and cellular mechanisms governing those intricate interactions would significantly advance our understanding of the etiology and pathogenesis of PD and aid the development of therapeutic strategies for the treatment of the disease. JF - Environmental health perspectives AU - Liu, Bin AU - Gao, Hui-Ming AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina, USA. liu3@niehs.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 1065 EP - 1073 VL - 111 IS - 8 SN - 0091-6765, 0091-6765 KW - Free Radicals KW - 0 KW - Pesticides KW - Receptors, Dopamine KW - Index Medicus KW - Age of Onset KW - Humans KW - Astrocytes -- physiology KW - Disease Progression KW - Aged KW - Brain -- immunology KW - Astrocytes -- immunology KW - Receptors, Dopamine -- physiology KW - Microglia -- physiology KW - Risk Factors KW - Brain -- pathology KW - Microglia -- immunology KW - Middle Aged KW - Infection -- complications KW - Parkinson Disease -- etiology KW - Pesticides -- poisoning KW - Environmental Exposure KW - Parkinson Disease -- physiopathology KW - Craniocerebral Trauma -- complications KW - Inflammation -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73407658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Parkinson%27s+disease+and+exposure+to+infectious+agents+and+pesticides+and+the+occurrence+of+brain+injuries%3A+role+of+neuroinflammation.&rft.au=Liu%2C+Bin%3BGao%2C+Hui-Ming%3BHong%2C+Jau-Shyong&rft.aulast=Liu&rft.aufirst=Bin&rft.date=2003-06-01&rft.volume=111&rft.issue=8&rft.spage=1065&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 - 2003-10-17 N1 - Date created - 2003-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Exp Neurol. 2001 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Neuropathology. 2001 Dec;21(4):315-22 [11837539] J Biol Chem. 2002 Feb 15;277(7):5411-7 [11724769] Brain Res Dev Brain Res. 2002 Jan 31;133(1):27-35 [11850061] J Neurosci. 2002 Mar 1;22(5):1763-71 [11880505] Neuroscience. 2002;110(1):49-58 [11882372] J Biochem. 2002 Apr;131(4):565-70 [11926994] J Neurosci. 2002 May 1;22(9):3484-92 [11978825] J Hist Neurosci. 2002 Mar;11(1):19-28 [12012571] Neurosci Lett. 2002 Jun 21;326(1):70-2 [12052541] J Neurochem. 2002 Jun;81(6):1285-97 [12068076] Trends Immunol. 2002 Jun;23(6):285-90 [12072366] Ann N Y Acad Sci. 2002 May;962:318-31 [12076984] Neurobiol Dis. 2002 Jul;10(2):119-27 [12127150] Clin Neurol Neurosurg. 2002 Sep;104(4):328-33 [12140099] Curr Opin Neurol. 2002 Aug;15(4):457-60 [12151843] Toxicol Appl Pharmacol. 1980 Mar 30;53(1):75-82 [6770493] Psychopharmacology (Berl). 1980;68(1):37-42 [6771797] J Immunol. 1982 Dec;129(6):2413-9 [6982921] J Neural Transm (Vienna). 2000;107(5):553-62 [11072751] Science. 1983 Feb 25;219(4587):979-80 [6823561] Biochem J. 1984 Dec 1;224(2):525-34 [6517863] South Med J. 1985 Feb;78(2):207-9 [3975719] Science. 1985 Jul 19;229(4710):257-8 [3925554] Surg Neurol. 1985 Sep;24(3):263-4 [4023906] Life Sci. 1985 Oct 21;37(16):1529-38 [3876500] Neurosci Lett. 1985 Dec 18;62(3):389-94 [3912685] J Exp Med. 1986 Aug 1;164(2):594-604 [3487617] Sports Med. 1987 May-Jun;4(3):194-210 [3296090] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystallographic analysis of a hydroxylated polychlorinated biphenyl (OH-PCB) bound to the catalytic estrogen binding site of human estrogen sulfotransferase. AN - 73403769; 12782487 AB - Certain hydroxylated polychlorinated biphenyls (OH-PCBs) inhibit the human estrogen sulfotransferase (hEST) at subnanomolar concentrations, suggesting a possible pathway for PCB toxicity due to environmental exposure in humans. To address the structural basis of the inhibition, we have determined the crystal structure of hEST in the presence of the sulfuryl donor product 3 -phosphoadenosine 5 -phosphate and the OH-PCB 4,4 -OH 3,5,3,5 -tetraCB. The OH-PCB binds in the estrogen binding site with the position of the first phenolic ring in an orientation similar to the phenolic ring of 17 beta-estradiol. Interestingly, the OH-PCB does not bind in a planar conformation, but rather with a 30-degree twist between the phenyl rings. The crystal structure of hEST with the OH-PCB bound gives physical evidence that certain OH-PCBs can mimic binding of estrogenic compounds in biological systems. JF - Environmental health perspectives AU - Shevtsov, Sergei AU - Petrotchenko, Evgeniy V AU - Pedersen, Lars C AU - Negishi, Masahiko AD - Pharmacogenetic Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 884 EP - 888 VL - 111 IS - 7 SN - 0091-6765, 0091-6765 KW - Estrogens KW - 0 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Sulfotransferases KW - EC 2.8.2.- KW - estrone sulfotransferase KW - EC 2.8.2.4 KW - Index Medicus KW - United States KW - Models, Molecular KW - Humans KW - Crystallography KW - Female KW - Hydroxylation KW - Binding Sites KW - Sulfotransferases -- metabolism KW - Estrogens -- metabolism KW - Sulfotransferases -- chemistry KW - Polychlorinated Biphenyls -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73403769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Crystallographic+analysis+of+a+hydroxylated+polychlorinated+biphenyl+%28OH-PCB%29+bound+to+the+catalytic+estrogen+binding+site+of+human+estrogen+sulfotransferase.&rft.au=Shevtsov%2C+Sergei%3BPetrotchenko%2C+Evgeniy+V%3BPedersen%2C+Lars+C%3BNegishi%2C+Masahiko&rft.aulast=Shevtsov&rft.aufirst=Sergei&rft.date=2003-06-01&rft.volume=111&rft.issue=7&rft.spage=884&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 - 2003-11-17 N1 - Date created - 2003-06-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Endocrinology. 2000 May;141(5):1897-900 [10803601] Environ Health Perspect. 1999 Aug;107 Suppl 4:639-49 [10421775] J Biol Chem. 2002 May 17;277(20):17928-32 [11884392] Endocrinology. 2002 Aug;143(8):3144-51 [12130580] Mol Pharmacol. 1988 Jan;33(1):120-6 [3122017] Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 [2025413] Breast Cancer Res Treat. 1992 Mar;20(3):145-54 [1571568] Cancer Res. 1996 Apr 1;56(7):1551-5 [8603401] Toxicol Appl Pharmacol. 1997 Jul;145(1):111-23 [9221830] Nat Struct Biol. 1997 Nov;4(11):904-8 [9360604] Environ Health Perspect. 1998 Feb;106 Suppl 1:5-10 [9539003] J Biol Chem. 1998 May 1;273(18):10888-92 [9556564] Chem Biol Interact. 1998 Feb 20;109(1-3):3-27 [9566730] Chem Biol Interact. 1998 Feb 20;109(1-3):293-7 [9566753] Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21 [9757107] Toxicol Appl Pharmacol. 1999 Jan 15;154(2):188-97 [9925803] Endocrinology. 2001 Dec;142(12):5342-50 [11713234] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Key issues for the assessment of the allergenic potential of genetically modified foods: breakout group reports. AN - 73400573; 12826486 AB - On the final afternoon of the workshop "Assessment of the Allergenic Potential of Genetically Modified Foods," held 10-12 December 2001 in Chapel Hill, North Carolina, USA, speakers and participants met in breakout groups to discuss specific questions in the areas of use of human clinical data, animal models to assess food allergy, biomarkers of exposure and effect, sensitive populations, dose-response assessment, and postmarket surveillance. Each group addressed general questions regarding allergenicity of genetically modified foods and specific questions for each subject area. This article is a brief summary of the discussions of each of the six breakout groups regarding our current state of knowledge and what information is needed to advance the field. JF - Environmental health perspectives AU - Germolec, Dori R AU - Kimber, Ian AU - Goldman, Lynn AU - Selgrade, MaryJane AD - Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. germolec@niehs.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 1131 EP - 1139 VL - 111 IS - 8 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Biomarkers -- analysis KW - Disease Models, Animal KW - Research Design KW - Risk Assessment KW - Food Hypersensitivity -- etiology KW - Product Surveillance, Postmarketing KW - Environmental Exposure KW - Clinical Trials as Topic KW - Food Hypersensitivity -- immunology KW - Food, Genetically Modified -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73400573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Key+issues+for+the+assessment+of+the+allergenic+potential+of+genetically+modified+foods%3A+breakout+group+reports.&rft.au=Germolec%2C+Dori+R%3BKimber%2C+Ian%3BGoldman%2C+Lynn%3BSelgrade%2C+MaryJane&rft.aulast=Germolec&rft.aufirst=Dori&rft.date=2003-06-01&rft.volume=111&rft.issue=8&rft.spage=1131&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 - 2003-10-17 N1 - Date created - 2003-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Clin Rev Allergy Immunol. 1999 Fall;17(3):323-38 [10597370] Toxicol Sci. 2000 Jun;55(2):343-51 [10828266] FEBS Lett. 2000 Jan 7;465(1):39-46 [10620703] J Pediatr Gastroenterol Nutr. 2000;30 Suppl:S77-86 [10634303] Food Chem Toxicol. 1999 Dec;37(12):1167-74 [10654593] J Allergy Clin Immunol. 2000 Mar;105(3):582-6 [10719311] Occup Med (Lond). 2000 Jan;50(1):25-9 [10795388] Clin Exp Allergy. 2000 Nov;30(11):1511-8 [11069558] JAMA. 2001 Apr 4;285(13):1746-8 [11277829] Int Arch Allergy Immunol. 2001 May;125(1):44-50 [11385287] Allergy. 2001 Jun;56(6):478-90 [11421891] J Investig Allergol Clin Immunol. 2001;11(2):89-93 [11642578] J Allergy Clin Immunol. 2002 Jan;109(1):24-30 [11799361] Curr Opin Allergy Clin Immunol. 2002 Apr;2(2):97-101 [11964756] Allergy. 2002 Aug;57(8):659-60 [12121181] Clin Exp Allergy. 2002 Dec;32(12):1757-62 [12653168] Environ Health Perspect. 2003 Jun;111(8):1140-1 [12826487] Clin Allergy. 1977 Jul;7(4):375-83 [73429] J Allergy Clin Immunol. 1978 Dec;62(6):327-34 [81844] Toxicol Appl Pharmacol. 1983 Apr;68(2):229-41 [6304938] Toxicol Appl Pharmacol. 1987 Jul;89(3):449-56 [3299874] J Allergy Clin Immunol. 1988 Jun;81(6):1180-6 [3379230] J Pediatr. 1988 Sep;113(3):447-51 [3411388] Acta Paediatr Scand. 1988 Sep;77(5):663-70 [3201972] J Allergy Clin Immunol. 1988 Dec;82(6):986-97 [3060514] J Allergy Clin Immunol. 1989 Feb;83(2 Pt 1):435-40 [2918186] J Allergy Clin Immunol. 1989 May;83(5):900-4 [2715549] J Allergy Clin Immunol. 1989 Nov;84(5 Pt 1):701-9 [2809025] J Allergy Clin Immunol. 1992 Mar;89(3):730-7 [1545094] Allergy. 1992 Dec;47(6):610-7 [1283656] J Allergy Clin Immunol. 1995 Sep;96(3):341-51 [7560636] Clin Rev Allergy Immunol. 1995 Winter;13(4):347-59 [8680954] BMJ. 1996 Aug 31;313(7056):518-21 [8789975] Crit Rev Food Sci Nutr. 1996;36 Suppl:S69-89 [8959379] Crit Rev Food Sci Nutr. 1996;36 Suppl:S91-118 [8959380] Crit Rev Food Sci Nutr. 1996;36 Suppl:S165-86 [8959382] Food Chem Toxicol. 1997 Mar-Apr;35(3-4):417-25 [9207904] J Allergy Clin Immunol. 1997 Nov;100(5):596-600 [9389287] JAMA. 1997 Dec 10;278(22):1888-94 [9396650] Clin Exp Allergy. 1998 Sep;28(9):1113-9 [9761015] Scand J Immunol. 1999 Jun;49(6):578-84 [10354369] Curr Microbiol. 1999 Jul;39(1):14-20 [10387111] Pediatr Allergy Immunol. 1999 Feb;10(1):27-32 [10410914] Food Chem Toxicol. 1999 May;37(5):553-60 [10456684] J Immunol. 1999 Sep 1;163(5):2944-52 [10453043] Ann Allergy Asthma Immunol. 1999 Dec;83(6 Pt 1):517-23 [10619342] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioral characterization of mice lacking the A3 adenosine receptor: sensitivity to hypoxic neurodegeneration. AN - 73393418; 12825837 AB - 1. The potential neuroprotective actions of the A3 adenosine receptor (A3AR) were investigated using mice with functional deletions of the A3AR (A3AR-/-) in behavioral assessments of analgesia, locomotion, tests predictive of depression and anxiety, and the effects of mild hypoxia on cognition and neuronal survival. 2. Untreated A3AR-/- mice were tested in standard behavioral paradigms, including activity in the open field, performance in the hot-plate, tail-flick, tail-suspension, and swim tests, and in the elevated plus maze. In addition, mice were exposed repeatedly to a hypoxic environment containing carbon monoxide (CO). The cognitive effects of this treatment were assessed using the contextual fear conditioning test. After testing, the density of pyramidal neurons in the CA1, 2, and 3 subfields of the hippocampus was determined using standard histological and morphometric techniques. 3. A3AR-/- mice showed increased locomotion in the open field test, elevated plus maze (number of arm entries) and light/dark box (number of transitions). However, they spent more time immobile in two different tests of antidepressant activity (Swim and tail suspension tests). A3AR-/- mice also showed evidence of decreased nociception in the hotplate, but not tail-flick tests. Further, A3AR-/- mice were more vulnerable to hippocampal pyramidal neuron damage following episodes of carbon monoxide (CO)-induced hypoxia. One week after exposure to CO a moderate loss of pyramidal neurons was observed in all hippocampal subfields of both wild-type (A3AR+/+) and A3AR-/- mice. However, the extent of neuronal death in the CA2-3 subfields was less pronounced in A3AR+/+ than A3AR-/- mice. This neuronal loss was accompanied by a decline in cognitive function as determined using contextual fear conditioning. These histological and cognitive changes were reproduced in wild-type mice by repeatedly administering the A3AR-selective antagonist MRS 1523 (5-propyl-2-ethyl-4-propyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate 1 mg/kg i.p.). 4. These results indicate that pharmacologic or genetic suppression of A3AR function enhances some aspects of motor function and suppresses pain processing at supraspinal levels, while acting as a depressant in tests predictive of antidepressant action. Consistent with previous reports of the neuroprotective actions of A3AR agonists, A3AR-/- mice show an increase in neurodegeneration in response to repeated episodes of hypoxia. JF - Cellular and molecular neurobiology AU - Fedorova, Irina M AU - Jacobson, Marlene A AU - Basile, Anthony AU - Jacobson, Kenneth A AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 431 EP - 447 VL - 23 IS - 3 SN - 0272-4340, 0272-4340 KW - 2,3-diethyl-4,5-dipropyl-6-phenylpyridine-3-thiocarboxylate-5-carboxylate KW - 0 KW - Purinergic P1 Receptor Antagonists KW - Pyridines KW - Receptor, Adenosine A3 KW - Receptors, Purinergic P1 KW - Index Medicus KW - Space life sciences KW - Animals KW - Cognition Disorders -- metabolism KW - Pain -- physiopathology KW - Maze Learning -- physiology KW - Pyramidal Cells -- metabolism KW - Depressive Disorder -- genetics KW - Cognition Disorders -- chemically induced KW - Mice, Knockout KW - Cell Survival -- drug effects KW - Cognition Disorders -- genetics KW - Motor Activity -- drug effects KW - Male KW - Pain -- metabolism KW - Motor Activity -- genetics KW - Pyramidal Cells -- drug effects KW - Maze Learning -- drug effects KW - Cell Survival -- genetics KW - Depressive Disorder -- chemically induced KW - Mice KW - Pyramidal Cells -- pathology KW - Pain Measurement -- drug effects KW - Pain -- genetics KW - Pyridines -- pharmacology KW - Depressive Disorder -- metabolism KW - Nerve Degeneration -- physiopathology KW - Hippocampus -- metabolism KW - Nerve Degeneration -- genetics KW - Receptors, Purinergic P1 -- genetics KW - Behavior, Animal -- drug effects KW - Hypoxia, Brain -- physiopathology KW - Receptors, Purinergic P1 -- deficiency KW - Nerve Degeneration -- metabolism KW - Hypoxia, Brain -- genetics KW - Hypoxia, Brain -- metabolism KW - Behavior, Animal -- physiology KW - Hippocampus -- physiopathology KW - Hippocampus -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73393418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+neurobiology&rft.atitle=Behavioral+characterization+of+mice+lacking+the+A3+adenosine+receptor%3A+sensitivity+to+hypoxic+neurodegeneration.&rft.au=Fedorova%2C+Irina+M%3BJacobson%2C+Marlene+A%3BBasile%2C+Anthony%3BJacobson%2C+Kenneth+A&rft.aulast=Fedorova&rft.aufirst=Irina&rft.date=2003-06-01&rft.volume=23&rft.issue=3&rft.spage=431&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+neurobiology&rft.issn=02724340&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-13 N1 - Date created - 2003-06-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Brain Res. 1994 May 30;647(1):57-64 [8069705] Br J Pharmacol. 1999 May;127(2):335-42 [10385231] Am J Physiol. 1999 Jun;276(6 Pt 2):H2076-84 [10362690] Mol Chem Neuropathol. 1998 Aug-Dec;35(1-3):39-59 [10343970] Eur J Neurosci. 1999 Jan;11(1):1-9 [9987006] Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10908-13 [9724803] J Neurosci. 1998 Aug 15;18(16):6138-46 [9698308] J Biol Chem. 2000 Feb 11;275(6):4429-34 [10660615] Biochim Biophys Acta. 2000 Mar 17;1500(3):280-90 [10699369] Neuroreport. 2000 Apr 7;11(5):1025-30 [10790877] FASEB J. 2000 Jul;14(10):1423-31 [10877835] Neuropharmacology. 2001;40(1):85-95 [11077074] J Mol Cell Cardiol. 2001 Apr;33(4):825-30 [11273734] Br J Pharmacol. 2001 Sep;134(1):68-77 [11522598] Am J Physiol Heart Circ Physiol. 2001 Oct;281(4):H1751-8 [11557567] Pharmacol Rev. 2001 Dec;53(4):527-52 [11734617] Cardiovasc Res. 2002 Jan;53(1):147-55 [11744023] J Mol Neurosci. 2001 Dec;17(3):285-92 [11859924] Circ Res. 2002 Mar 22;90(5):531-8 [11909816] Am J Physiol Heart Circ Physiol. 2002 Jun;282(6):H2183-9 [12003827] Glia. 2002 May;38(3):179-90 [11968056] Oncogene. 2002 Jun 6;21(25):4060-4 [12037688] Eur J Neurosci. 2002 Aug;16(3):547-50 [12193199] FEBS Lett. 2002 Dec 18;532(3):267-72 [12482577] Eur J Pharmacol. 1979 Aug 1;57(2-3):201-10 [488159] Psychopharmacology (Berl). 1985;85(3):367-70 [3923523] J Pharmacol Exp Ther. 1991 Jan;256(1):378-84 [1671097] Biochem Biophys Res Commun. 1991 Sep 16;179(2):836-40 [1832862] J Biol Chem. 1993 Aug 15;268(23):16887-90 [8349579] FEBS Lett. 1993 Dec 20;336(1):57-60 [8262217] Eur J Pharmacol. 1994 Sep 22;263(1-2):59-67 [7821362] Circ Res. 1996 Apr;78(4):627-34 [8635220] J Immunol. 1996 May 1;156(9):3435-42 [8617970] Eur J Pharmacol. 1996 Jul 25;308(3):311-4 [8858305] J Neurosci. 1997 Jan 15;17(2):607-14 [8987783] Neuropharmacology. 1997 Sep;36(9):1157-65 [9364471] Trends Pharmacol Sci. 1998 May;19(5):184-91 [9652191] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peptides: their role in excess alcohol drinking and their promise as a therapeutic tool. AN - 73389697; 12818713 JF - Physiology & behavior AU - Egli, Mark AD - Division of Basic Research, The National Institute on Alcoholism and Alcohol Abuse, National Institutes of Health, Department of Health and Human Services, 6000 Executive Boulevard, Bethesda, MD 20892, USA. megli@willco.niaaa.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 89 EP - 93 VL - 79 IS - 1 SN - 0031-9384, 0031-9384 KW - Leptin KW - 0 KW - Neuropeptide Y KW - Neuropeptides KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Rats KW - Animals KW - Substance Withdrawal Syndrome -- physiopathology KW - Motivation KW - Humans KW - Substance Withdrawal Syndrome -- genetics KW - Ethanol -- toxicity KW - Disease Models, Animal KW - Leptin -- physiology KW - Leptin -- genetics KW - Neuropeptide Y -- physiology KW - Neuropeptide Y -- genetics KW - Alcoholism -- rehabilitation KW - Neuropeptides -- physiology KW - Alcohol Drinking -- physiopathology KW - Alcohol Drinking -- prevention & control KW - Alcoholism -- physiopathology KW - Alcohol Drinking -- genetics KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73389697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Physiology+%26+behavior&rft.atitle=Peptides%3A+their+role+in+excess+alcohol+drinking+and+their+promise+as+a+therapeutic+tool.&rft.au=Egli%2C+Mark&rft.aulast=Egli&rft.aufirst=Mark&rft.date=2003-06-01&rft.volume=79&rft.issue=1&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Physiology+%26+behavior&rft.issn=00319384&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-09 N1 - Date created - 2003-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Management of surgically hypogonadal patients unable to take sex hormone replacement therapy. AN - 73380193; 12800534 AB - Lifestyle changes in diet, exercise and the environment may help to prevent or ameliorate hot flashes and low bone density in men and women after surgical castration. Conventional medications, including megestrol acetate, SSRIs or clonidine, may improve hot flashes but may have limiting side effects. Some complementary and alternative approaches, including black cohosh, vitamin E, and soy products, work as well as placebo to decrease hot flashes and may be helpful, because they have low toxicity. Acupuncture and neurontin are promising but must be studied further. With regards to the prevention of osteoporosis and fractures in men and women, bisphosphonates are the most potent of the currently available agents; calcitonin is less effective. PTH has a large beneficial effect but is not yet available and is less well studied. In women, continued sexual intercourse and use of vaginal lubricants and moisturizers help to minimize symptoms of vaginal atrophy but do not ameliorate urinary symptoms. Low dose local estrogen treatment is a promising approach for the latter complaints. JF - Endocrinology and metabolism clinics of North America AU - Nieman, Lynnette K AD - Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 9D42 MSC 1583, 10 Center Drive, Bethesda, MD 20892, USA. NiemanL@nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 325 EP - 336 VL - 32 IS - 2 SN - 0889-8529, 0889-8529 KW - Serotonin Uptake Inhibitors KW - 0 KW - Megestrol Acetate KW - TJ2M0FR8ES KW - Index Medicus KW - Life Style KW - Megestrol Acetate -- therapeutic use KW - Vaginitis -- therapy KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Humans KW - Soy Foods KW - Trifolium -- metabolism KW - Male KW - Female KW - Osteoporosis -- prevention & control KW - Orchiectomy -- adverse effects KW - Hypogonadism -- etiology KW - Ovariectomy -- adverse effects KW - Hot Flashes -- therapy KW - Hypogonadism -- therapy KW - Estrogen Replacement Therapy -- contraindications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73380193?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology+and+metabolism+clinics+of+North+America&rft.atitle=Management+of+surgically+hypogonadal+patients+unable+to+take+sex+hormone+replacement+therapy.&rft.au=Nieman%2C+Lynnette+K&rft.aulast=Nieman&rft.aufirst=Lynnette&rft.date=2003-06-01&rft.volume=32&rft.issue=2&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Endocrinology+and+metabolism+clinics+of+North+America&rft.issn=08898529&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-10 N1 - Date created - 2003-06-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term mitochondrial toxicity in HIV-uninfected infants born to HIV-infected mothers. AN - 73367047; 12794551 AB - Although children born to HIV-infected (HIV+) women receiving antiretroviral therapy during pregnancy show virtually no adverse clinical effects at birth, the antiretroviral nucleoside analog drugs are known to damage nuclear and mitochondrial DNA. In this study, biomarkers of mitochondrial toxicity and genotoxicity have been examined in a well-characterized sample set consisting of infants born to HIV-uninfected (HIV-) mothers (n = 30), and HIV- infants (n = 20) born to HIV-infected (HIV+) mothers who received either no antiretroviral therapy (n = 10) or zidovudine (3'-azido-3'-deoxythymidine [AZT]) during pregnancy (n = 10). DNA from cord blood leukocytes and peripheral blood leukocytes taken at 1 and 2 years of age was examined for loss of mitochondrial DNA (mtDNA) and telomere integrity. Telomere length, a measure of nuclear DNA damage, was the same in all infants at birth and at age 1 year. The quantity of mtDNA was assessed relative to nuclear DNA using a polymerase chain reaction-based chemiluminescence detection (PCR-CID) method that determined mitochondrial D Loop gene copies relative to nuclear 18S RNA gene copies by comparison with a standard curve. MtDNA quantity was expressed as a ratio of gene copy numbers. In infants of uninfected mothers (AZT-/HIV-) at the three time points, the ratios were 442 to 515, whereas in infants of untreated AZT-/HIV+ mothers the ratios were 261 to 297, and in infants of AZT-treated (AZT+/HIV+) mothers the ratios were 146 to 203. At all three time points, differences between the AZT-/HIV- group and the two HIV+ groups were statistically significant (p <.05), and differences between the AZT-/HIV+ and AZT+/HIV+ groups were also statistically significant (p <.05), demonstrating that AZT exposure causes a persistent depletion of mtDNA. The study shows that children of HIV+ mothers are at risk for mitochondrial damage that is further increased in infants of mothers receiving AZT during pregnancy. JF - Journal of acquired immune deficiency syndromes (1999) AU - Poirier, Miriam C AU - Divi, Rao L AU - Al-Harthi, Lena AU - Olivero, Ofelia A AU - Nguyen, Vi AU - Walker, Brettania AU - Landay, Alan L AU - Walker, Vernon E AU - Charurat, Manhattan AU - Blattner, William A AU - Women and Infants Transmission Study (WITS) Group AD - Carcinogen-DNA Interactions Section, National Cancer Institute, National Institutes of Health, Building 37, Room 4032, 37 Convent Drive, Bethesda, MD 20892-4255, USA. poirierm@exchange.nih.gov ; Women and Infants Transmission Study (WITS) Group Y1 - 2003/06/01/ PY - 2003 DA - 2003 Jun 01 SP - 175 EP - 183 VL - 33 IS - 2 SN - 1525-4135, 1525-4135 KW - DNA, Mitochondrial KW - 0 KW - Genetic Markers KW - RNA, Ribosomal, 18S KW - Reverse Transcriptase Inhibitors KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Fetal Blood -- immunology KW - Humans KW - Telomere -- ultrastructure KW - Infant, Newborn KW - Pilot Projects KW - RNA, Ribosomal, 18S -- drug effects KW - Child, Preschool KW - Pregnancy KW - Infant KW - Prospective Studies KW - Telomere -- drug effects KW - Adult KW - Female KW - RNA, Ribosomal, 18S -- analysis KW - Reverse Transcriptase Inhibitors -- adverse effects KW - DNA, Mitochondrial -- drug effects KW - Zidovudine -- adverse effects KW - HIV Infections -- blood KW - Leukocytes, Mononuclear -- chemistry KW - HIV Infections -- drug therapy KW - DNA, Mitochondrial -- analysis KW - HIV Infections -- genetics KW - Leukocytes, Mononuclear -- drug effects KW - Pregnancy Complications, Infectious -- drug therapy KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73367047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+acquired+immune+deficiency+syndromes+%281999%29&rft.atitle=Long-term+mitochondrial+toxicity+in+HIV-uninfected+infants+born+to+HIV-infected+mothers.&rft.au=Poirier%2C+Miriam+C%3BDivi%2C+Rao+L%3BAl-Harthi%2C+Lena%3BOlivero%2C+Ofelia+A%3BNguyen%2C+Vi%3BWalker%2C+Brettania%3BLanday%2C+Alan+L%3BWalker%2C+Vernon+E%3BCharurat%2C+Manhattan%3BBlattner%2C+William+A%3BWomen+and+Infants+Transmission+Study+%28WITS%29+Group&rft.aulast=Poirier&rft.aufirst=Miriam&rft.date=2003-06-01&rft.volume=33&rft.issue=2&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes+%281999%29&rft.issn=15254135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-29 N1 - Date created - 2003-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dual phosphorylation controls Cdc25 phosphatases and mitotic entry. AN - 73356483; 12766774 AB - Negative regulation of the Cdc25C protein phosphatase by phosphorylation on Ser 216, the 14-3-3-binding site, is an important regulatory mechanism used by cells to block mitotic entry under normal conditions and after DNA damage. During mitosis, Cdc25C is not phosphorylated on Ser 216 and ionizing radiation (IR) does not induce either phosphorylation of Ser 216, or binding to 14-3-3. Here, we show that Cdc25C is phosphorylated on Ser 214 during mitosis, which in turn prevents phosphorylation of Ser 216. Mutation of Ser 214 to Ala reconstitutes Ser 216 phosphorylation and 14-3-3 binding during mitosis. Introduction of exogenous Cdc25C(S214A) into HeLa cells depleted of endogenous Cdc25C results in a substantial delay to mitotic entry. This effect was fully reversed in a S214A/S216A double-mutant, implying that the inhibitory effect of S214A mutant was entirely dependent on Ser 216 phosphorylation. A similar regulatory mechanism may also apply to another mitotic phosphatase, Cdc25B, as well as mitotic phosphatases of other species, including Xenopus laevis. We propose that this pathway ensures that Cdc2 remains active once mitosis is initiated and is a key control mechanism for maintaining the proper order of cell-cycle transitions. JF - Nature cell biology AU - Bulavin, Dmitry V AU - Higashimoto, Yuichiro AU - Demidenko, Zoya N AU - Meek, Sarah AU - Graves, Paul AU - Phillips, Crissy AU - Zhao, Hui AU - Moody, Sally A AU - Appella, Ettore AU - Piwnica-Worms, Helen AU - Fornace, Albert J AD - Gene Response Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 545 EP - 551 VL - 5 IS - 6 SN - 1465-7392, 1465-7392 KW - 14-3-3 Proteins KW - 0 KW - Antineoplastic Agents KW - Serine KW - 452VLY9402 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - cdc25 Phosphatases KW - EC 3.1.3.48 KW - Alanine KW - OF5P57N2ZX KW - Nocodazole KW - SH1WY3R615 KW - Index Medicus KW - DNA Damage KW - HeLa Cells KW - Humans KW - Tyrosine 3-Monooxygenase -- chemistry KW - Protein Binding KW - Nocodazole -- pharmacology KW - Serine -- metabolism KW - Mutagenesis, Site-Directed KW - G2 Phase -- physiology KW - Phosphorylation KW - Alanine -- metabolism KW - Point Mutation KW - Antineoplastic Agents -- pharmacology KW - Amino Acid Substitution KW - Radiation, Ionizing KW - Mitosis KW - cdc25 Phosphatases -- genetics KW - cdc25 Phosphatases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73356483?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+cell+biology&rft.atitle=Dual+phosphorylation+controls+Cdc25+phosphatases+and+mitotic+entry.&rft.au=Bulavin%2C+Dmitry+V%3BHigashimoto%2C+Yuichiro%3BDemidenko%2C+Zoya+N%3BMeek%2C+Sarah%3BGraves%2C+Paul%3BPhillips%2C+Crissy%3BZhao%2C+Hui%3BMoody%2C+Sally+A%3BAppella%2C+Ettore%3BPiwnica-Worms%2C+Helen%3BFornace%2C+Albert+J&rft.aulast=Bulavin&rft.aufirst=Dmitry&rft.date=2003-06-01&rft.volume=5&rft.issue=6&rft.spage=545&rft.isbn=&rft.btitle=&rft.title=Nature+cell+biology&rft.issn=14657392&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-14 N1 - Date created - 2003-05-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Factors associated with volatile solvent use among junior high school students in Kanto, Japan. AN - 73346116; 12780365 AB - To estimate the relative association between life-time volatile solvent use and risk factors for usage. Cross-sectional anonymous questionnaire survey. Junior high schools in Kanto, Japan. Junior high school students (n = 7744). Data on life-time and past-year solvent use, demographic variables, urbanization, regularity of waking patterns, school life, family life, peer relationships, prior alcohol and cigarette use and knowledge on harmful effects of solvent use. Uni- and multivariate logistic regression analyses were conducted to estimate crude and adjusted odds ratios for each index. The primary findings were (1) 'smoking cigarettes nearly every day' (adjusted OR = 9.88, 95% Cl = 3.74, 26.12) and peer pressure measured by 'been tempted to use solvents' (adjusted OR = 9.53, 95% Cl = 4.84, 18.74) demonstrated the highest adjusted odds ratios; (2) being male (adjusted OR = 2.56, 95% Cl = 1.37, 4.76), seeing school life as 'not at all enjoyable' (adjusted OR = 2.69, 95% Cl = 1.03, 7.01) and family environment as 'neither good nor bad' (adjusted OR = 2.15, 95% Cl = 1.19, 3.88) also showed significant association; (3) life-time alcohol use did not show a significant association in the multivariate model (adjusted OR = 0.80, 95% Cl = 0.30, 2.12); and (4) solvent use appeared independent of knowledge regarding its effects ('death by acute intoxication', 'psychotic symptoms', 'amotivational syndrome', 'flashbacks' adjusted ORs all non-significant). Alcohol use may not function as a gateway to solvent use in Japan. The reasons may be culture-bound. A longitudinal study is required to test this hypothesis. JF - Addiction (Abingdon, England) AU - Kikuchi, Akiko AU - Wada, Kiyoshi AD - Division of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba-ken, Japan. soudan1@har.u-tokyo.ac.jp Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 771 EP - 784 VL - 98 IS - 6 SN - 0965-2140, 0965-2140 KW - Solvents KW - 0 KW - Index Medicus KW - Analysis of Variance KW - Sex Factors KW - Humans KW - Interpersonal Relations KW - Child KW - Smoking -- psychology KW - Peer Group KW - Cross-Sectional Studies KW - Logistic Models KW - Risk Factors KW - Surveys and Questionnaires KW - Adolescent KW - Female KW - Japan KW - Male KW - Adolescent Behavior KW - Substance-Related Disorders -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73346116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Factors+associated+with+volatile+solvent+use+among+junior+high+school+students+in+Kanto%2C+Japan.&rft.au=Kikuchi%2C+Akiko%3BWada%2C+Kiyoshi&rft.aulast=Kikuchi&rft.aufirst=Akiko&rft.date=2003-06-01&rft.volume=98&rft.issue=6&rft.spage=771&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 - 2003-08-14 N1 - Date created - 2003-06-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impact of establishing a primary stroke center at a community hospital on the use of thrombolytic therapy: the NINDS Suburban Hospital Stroke Center experience. AN - 73342406; 12750543 AB - To increase the proportion of ischemic stroke patients treated with thrombolytic therapy, the establishment of primary stroke centers in community hospitals has been advocated. We evaluated the use of thrombolytic therapy before and after institution of a primary stroke center in a community hospital. The availability of an on-call stroke emergency response team was the only significant additional resource required for this hospital. All eligible patients were treated with intravenous tissue plasminogen activator (tPA). The number of patients with cerebrovascular disease, number and proportion of patients treated with tPA, times to treatment, and patient outcomes were recorded during the first 2 years of the stroke center. During the 12 months before institution of the stroke center, 3 ischemic stroke patients (1.5%) were treated with tPA. During the 2-year period of around-the-clock coverage, 44 of 420 ischemic stroke patients (10.5%) were treated with intravenous tPA, a significant increase in tPA use (P<0.0001). Establishment of a primary stroke center at a community hospital resulted in a substantial increase in the proportion of patients receiving thrombolytic therapy for ischemic stroke. If this experience is generalized, the beneficial impact of primary stroke centers on stroke outcomes and costs to the healthcare system may be substantial. JF - Stroke AU - Lattimore, Susan Unipan AU - Chalela, Julio AU - Davis, Lisa AU - DeGraba, Thomas AU - Ezzeddine, Mustapha AU - Haymore, Joseph AU - Nyquist, Paul AU - Baird, Alison E AU - Hallenbeck, John AU - Warach, Steven AU - NINDS Suburban Hospital Stroke Center AD - Stroke Branch, National Institute of Neurological Disorders and Stroke, 10 Center Dr, MSC 1063, Building 10, Room B1D733, Bethesda, Md 20892-1063, USA. ; NINDS Suburban Hospital Stroke Center Y1 - 2003/06// PY - 2003 DA - June 2003 SP - e55 EP - e57 VL - 34 IS - 6 KW - Fibrinolytic Agents KW - 0 KW - Tissue Plasminogen Activator KW - EC 3.4.21.68 KW - Index Medicus KW - Fibrinolytic Agents -- therapeutic use KW - Cerebral Hemorrhage -- chemically induced KW - Brain Ischemia -- economics KW - Humans KW - Fibrinolytic Agents -- adverse effects KW - Aged KW - Pilot Projects KW - Recovery of Function -- drug effects KW - Triage -- statistics & numerical data KW - Brain Ischemia -- therapy KW - Mass Screening KW - Brain Ischemia -- diagnosis KW - Tissue Plasminogen Activator -- therapeutic use KW - Aged, 80 and over KW - Adult KW - Critical Pathways KW - Tissue Plasminogen Activator -- adverse effects KW - Middle Aged KW - Maryland KW - Time Factors KW - Male KW - Female KW - Emergency Service, Hospital -- organization & administration KW - Stroke -- therapy KW - Emergency Service, Hospital -- manpower KW - Outcome Assessment (Health Care) -- statistics & numerical data KW - Stroke -- diagnosis KW - Emergency Service, Hospital -- economics KW - Stroke -- economics KW - Patient Care Team -- organization & administration KW - Thrombolytic Therapy -- utilization KW - Hospitals, Community -- organization & administration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73342406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stroke&rft.atitle=Impact+of+establishing+a+primary+stroke+center+at+a+community+hospital+on+the+use+of+thrombolytic+therapy%3A+the+NINDS+Suburban+Hospital+Stroke+Center+experience.&rft.au=Lattimore%2C+Susan+Unipan%3BChalela%2C+Julio%3BDavis%2C+Lisa%3BDeGraba%2C+Thomas%3BEzzeddine%2C+Mustapha%3BHaymore%2C+Joseph%3BNyquist%2C+Paul%3BBaird%2C+Alison+E%3BHallenbeck%2C+John%3BWarach%2C+Steven%3BNINDS+Suburban+Hospital+Stroke+Center&rft.aulast=Lattimore&rft.aufirst=Susan&rft.date=2003-06-01&rft.volume=34&rft.issue=6&rft.spage=e55&rft.isbn=&rft.btitle=&rft.title=Stroke&rft.issn=1524-4628&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-26 N1 - Date created - 2003-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular neuroadaptations in the accumbens and ventral tegmental area during the first 90 days of forced abstinence from cocaine self-administration in rats. AN - 73342176; 12787079 AB - Cocaine self-administration is associated with a propensity to relapse in humans and reinstatement of drug seeking in rats after prolonged withdrawal periods. These behaviors are hypothesized to be mediated by molecular neuroadaptations within the mesolimbic dopamine system. However, in most studies of drug-induced neuroadaptations, cocaine was experimenter-delivered and molecular measurements were performed after short withdrawal periods. In the present study, rats were trained to self-administer intravenous cocaine or oral sucrose (a control non-drug reward) for 10 days (6-h/day) and were killed following 1, 30, or 90 days of reward withdrawal. Tissues from the accumbens and ventral tegmental area (VTA) were assayed for candidate molecular neuroadaptations, including enzyme activities of cAMP-dependent protein kinase (PKA) and adenylate cyclase (AC), and protein expression of cyclin-dependent kinase 5 (cdk5), tyrosine hydroxylase (TH) and glutamate receptor subunits (GluR1, GluR2 and NMDAR1). In the accumbens of cocaine-trained rats, GluR1 and NMDAR1 levels were increased on days 1 and 90, while GluR2 levels were increased on days 1 and 30, but not day 90; PKA activity levels were increased on days 1 and 30, but not day 90, while AC activity, TH and cdk5 levels were unaltered. In the VTA of cocaine-trained rats, NMDAR1 levels were increased for up to 90 days, while GluR2 levels were increased only on day 1; TH and Cdk5 levels were increased only on day 1, while PKA and AC activity levels were unaltered. Cocaine self-administration produces long-lasting molecular neuroadaptations in the VTA and accumbens that may underlie cocaine relapse during periods of abstinence. JF - Journal of neurochemistry AU - Lu, Lin AU - Grimm, Jeff W AU - Shaham, Yavin AU - Hope, Bruce T AD - Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, Maryland 21224, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 1604 EP - 1613 VL - 85 IS - 6 SN - 0022-3042, 0022-3042 KW - NR1 NMDA receptor KW - 0 KW - Receptors, AMPA KW - Receptors, N-Methyl-D-Aspartate KW - glutamate receptor ionotropic, AMPA 1 KW - glutamate receptor ionotropic, AMPA 2 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Cyclin-Dependent Kinase 5 KW - EC 2.7.11.1 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Cdk5 protein, rat KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinases KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Cyclin-Dependent Kinases -- metabolism KW - Animals KW - Tyrosine 3-Monooxygenase -- metabolism KW - Rats, Long-Evans KW - Adenylyl Cyclases -- metabolism KW - Disease Models, Animal KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Receptors, AMPA -- metabolism KW - Rats KW - Adaptation, Physiological -- drug effects KW - Blotting, Western KW - Self Administration KW - Time Factors KW - Male KW - Substance Withdrawal Syndrome -- metabolism KW - Nucleus Accumbens -- drug effects KW - Nucleus Accumbens -- metabolism KW - Ventral Tegmental Area -- metabolism KW - Cocaine-Related Disorders -- metabolism KW - Cocaine -- adverse effects KW - Cocaine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73342176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+neuroadaptations+in+the+accumbens+and+ventral+tegmental+area+during+the+first+90+days+of+forced+abstinence+from+cocaine+self-administration+in+rats.&rft.au=Lu%2C+Lin%3BGrimm%2C+Jeff+W%3BShaham%2C+Yavin%3BHope%2C+Bruce+T&rft.aulast=Lu&rft.aufirst=Lin&rft.date=2003-06-01&rft.volume=85&rft.issue=6&rft.spage=1604&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 - 2003-07-10 N1 - Date created - 2003-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antiangiogenic therapy through copper chelation. AN - 73340886; 12783576 AB - As new compounds are being evaluated for use in clinical trials involving antiangiogenic therapies, two important factors must be considered. Independent of clinical efficacy, the potential drug must be cost-effective and have reasonable ease of production. The compound endostatin (Entremed, Inc.) has recently completed two Phase I trials with minimal toxicity to the patients treated [1,2]. However, due to the difficulty and expense of producing large quantities of a recombinant protein, Entremed Inc. has experienced financial difficulties [3]. As this company's fate indicates, a drug must not only be clinically effective, but must also possess reasonable production economics. Another interesting component of compound development is selectivity. Highly selective antiangiogenic compounds such as the tyrosine kinase inhibitor SU-5416 are being replaced by less selective compounds such as SU-6668, which acts on a broader spectrum of tyrosine kinase receptors [4]. This move towards using less selective antiangiogenic compounds is based on preclinical models that demonstrate both better clinical efficacy when using less specific molecules and low response rates from the more selective compounds. With the aim of further examining broadly-acting antiangiogenic agents, the authors are currently evaluating new classes of agents that preferentially bind copper and inhibit angiogenesis. Copper has been known to be a significant target for antiangiogenic therapy for a number of years [5]. Recently, through the use of molecular techniques, the target enzymes that utilise copper as a cofactor are being elucidated. This review will describe the historical use of anticopper therapy for the treatment of Wilson's disease and evaluate some of the new anticopper compounds currently under consideration for use in antiangiogenic therapy. JF - Expert opinion on therapeutic targets AU - Sproull, Mary AU - Brechbiel, Martin AU - Camphausen, Kevin AD - Imaging and Molecular Therapeutics Section, Radiation Oncology Branch, Radiation Oncology Sciences Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, B3B69, Bethesda, MD, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 405 EP - 409 VL - 7 IS - 3 KW - Angiogenesis Inhibitors KW - 0 KW - Chelating Agents KW - Cyclohexylamines KW - Pyridines KW - tachpyr KW - Copper KW - 789U1901C5 KW - Molybdenum KW - 81AH48963U KW - tetrathiomolybdate KW - 91U3TGV99T KW - Penicillamine KW - GNN1DV99GX KW - Trientine KW - SJ76Y07H5F KW - Index Medicus KW - Trientine -- pharmacology KW - Animals KW - Neoplasms -- drug therapy KW - Penicillamine -- pharmacology KW - Molybdenum -- pharmacology KW - Humans KW - Rabbits KW - Pyridines -- therapeutic use KW - Cyclohexylamines -- pharmacology KW - Neoplasms -- blood supply KW - Neovascularization, Pathologic -- drug therapy KW - Corneal Neovascularization -- drug therapy KW - Trientine -- therapeutic use KW - Hepatolenticular Degeneration -- drug therapy KW - Molybdenum -- therapeutic use KW - Pyridines -- pharmacology KW - Penicillamine -- therapeutic use KW - Cyclohexylamines -- therapeutic use KW - Angiogenesis Inhibitors -- therapeutic use KW - Chelating Agents -- pharmacology KW - Angiogenesis Inhibitors -- pharmacology KW - Chelating Agents -- therapeutic use KW - Chelation Therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73340886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapeutic+targets&rft.atitle=Antiangiogenic+therapy+through+copper+chelation.&rft.au=Sproull%2C+Mary%3BBrechbiel%2C+Martin%3BCamphausen%2C+Kevin&rft.aulast=Sproull&rft.aufirst=Mary&rft.date=2003-06-01&rft.volume=7&rft.issue=3&rft.spage=405&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+therapeutic+targets&rft.issn=1744-7631&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-03-23 N1 - Date created - 2003-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - AIDS-related insulin resistance and lipodystrophy syndrome. AN - 73339003; 12769783 AB - The recent development of highly active antiretroviral therapy (HAART) has drastically improved the life expectancy of AIDS patients, by reducing infection-related mortality. However, the prolongation of the lives of HIV-1-infected patients and/or the long-term use of novel, potent antiviral agents have generated a score of new problems and complications. Among them is the AIDS-related insulin resistance and lipodystrophy syndrome, which is observed in 30-80% of AIDS patients who are well controlled by HAART. This syndrome is associated with severe metabolic disturbances, such as carbohydrate intolerance/diabetes mellitus and dyslipidemia, which cause atherosclerotic cardiovascular disease. The etiology of this syndrome appears to be multi-factorial; other than the anti-viral drugs, hypercytokinemia and the HIV-1 infection itself, including the virally encoded molecules Vpr and Tat, could contribute to the development of these pathologic changes or increase the vulnerability of patients to the adverse effect of the therapeutic compounds. In this article, we review our current understanding of the pathogenesis and therapeutic approach of this newly emerging AIDS-associated metabolic syndrome. JF - Current drug targets. Immune, endocrine and metabolic disorders AU - Kino, Tomoshige AU - Chrousos, George P AD - Pediatric and Reproductive Endocrinology Branch. National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1583, USA. kinot@mail.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 111 EP - 117 VL - 3 IS - 2 SN - 1568-0088, 1568-0088 KW - Index Medicus KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - Animals KW - Humans KW - Acquired Immunodeficiency Syndrome -- complications KW - HIV-Associated Lipodystrophy Syndrome -- drug therapy KW - Acquired Immunodeficiency Syndrome -- drug therapy KW - Insulin Resistance KW - HIV-Associated Lipodystrophy Syndrome -- metabolism KW - HIV-Associated Lipodystrophy Syndrome -- complications KW - Acquired Immunodeficiency Syndrome -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73339003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+drug+targets.+Immune%2C+endocrine+and+metabolic+disorders&rft.atitle=AIDS-related+insulin+resistance+and+lipodystrophy+syndrome.&rft.au=Kino%2C+Tomoshige%3BChrousos%2C+George+P&rft.aulast=Kino&rft.aufirst=Tomoshige&rft.date=2003-06-01&rft.volume=3&rft.issue=2&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Current+drug+targets.+Immune%2C+endocrine+and+metabolic+disorders&rft.issn=15680088&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-17 N1 - Date created - 2003-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results. AN - 73335285; 12788870 AB - Measurements of plasma normetanephrine and metanephrine provide a highly sensitive test for diagnosis of pheochromocytoma, but false-positive results remain a problem. We therefore assessed medication-associated false-positive results and use of supplementary tests, including plasma normetanephrine responses to clonidine, to distinguish true- from false-positive results. The study included 208 patients with pheochromocytoma and 648 patients in whom pheochromocytoma was excluded. Clonidine-suppression tests were carried out in 48 patients with and 49 patients without the tumor. Tricyclic antidepressants and phenoxybenzamine accounted for 41% of false-positive elevations of plasma normetanephrine and 44-45% those of plasma and urinary norepinephrine. High plasma normetanephrine to norepinephrine or metanephrine to epinephrine ratios were strongly predictive of pheochromocytoma. Lack of decrease and elevated plasma levels of norepinephrine or normetanephrine after clonidine also confirmed pheochromocytoma with high specificity. However, 16 of 48 patients with pheochromocytoma had normal levels or decreases of norepinephrine after clonidine. In contrast, plasma normetanephrine remained elevated in all but 2 patients, indicating more reliable diagnosis using normetanephrine than norepinephrine responses to clonidine. Thus, in patients with suspected pheochromocytoma and positive biochemical results, false-positive elevations due to medications should first be eliminated. Patterns of biochemical test results and responses of plasma normetanephrine to clonidine can then help distinguish true- from false-positive results. JF - The Journal of clinical endocrinology and metabolism AU - Eisenhofer, Graeme AU - Goldstein, David S AU - Walther, McClellan M AU - Friberg, Peter AU - Lenders, Jacques W M AU - Keiser, Harry R AU - Pacak, Karel AD - Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. ge@box-g.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 2656 EP - 2666 VL - 88 IS - 6 SN - 0021-972X, 0021-972X KW - Adrenergic alpha-Antagonists KW - 0 KW - Antidepressive Agents, Tricyclic KW - Normetanephrine KW - 0J45DE6B88 KW - Phenoxybenzamine KW - 0TTZ664R7Z KW - Clonidine KW - MN3L5RMN02 KW - Norepinephrine KW - X4W3ENH1CV KW - Abridged Index Medicus KW - Index Medicus KW - Drug Interactions KW - Humans KW - Norepinephrine -- blood KW - Antidepressive Agents, Tricyclic -- adverse effects KW - Normetanephrine -- urine KW - Adrenergic alpha-Antagonists -- adverse effects KW - Phenoxybenzamine -- adverse effects KW - False Positive Reactions KW - Norepinephrine -- urine KW - Adult KW - Middle Aged KW - Female KW - Male KW - Normetanephrine -- blood KW - Pheochromocytoma -- urine KW - Biochemistry -- methods KW - Adrenal Gland Neoplasms -- blood KW - Pheochromocytoma -- diagnosis KW - Adrenal Gland Neoplasms -- urine KW - Pheochromocytoma -- drug therapy KW - Adrenal Gland Neoplasms -- diagnosis KW - Pheochromocytoma -- blood KW - Adrenal Gland Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73335285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Biochemical+diagnosis+of+pheochromocytoma%3A+how+to+distinguish+true-+from+false-positive+test+results.&rft.au=Eisenhofer%2C+Graeme%3BGoldstein%2C+David+S%3BWalther%2C+McClellan+M%3BFriberg%2C+Peter%3BLenders%2C+Jacques+W+M%3BKeiser%2C+Harry+R%3BPacak%2C+Karel&rft.aulast=Eisenhofer&rft.aufirst=Graeme&rft.date=2003-06-01&rft.volume=88&rft.issue=6&rft.spage=2656&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-01 N1 - Date created - 2003-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic lithium administration potentiates brain arachidonic acid signaling at rest and during cholinergic activation in awake rats. AN - 73334869; 12787074 AB - Studies were performed to determine if the reported 'proconvulsant' action of lithium in rats given cholinergic drugs is related to receptor-initiated phospholipase A2 signaling via arachidonic acid. Regional brain incorporation coefficients k* of intravenously injected [1-14C]arachidonic acid, which represent this signaling, were measured by quantitative autoradiography in unanesthetized rats at baseline and following administration of subconvulsant doses of the cholinergic muscarinic agonist, arecoline. In rats fed LiCl for 6 weeks to produce a therapeutically relevant brain lithium concentration, the mean baseline values of k* in brain auditory and visual areas were significantly greater than in rats fed control diet. Arecoline at doses of 2 and 5 mg/kg intraperitoneally increased k* in widespread brain areas in rats fed the control diet as well as the LiCl diet. However, the arecoline-induced increments often were significantly greater in the LiCl-fed than in the control diet-fed rats. Lithium's elevation of baseline k* in auditory and visual regions may correspond to its ability in humans to increase auditory and visual evoked responses. Additionally, its augmentation of the k* responses to arecoline may underlie its reported 'proconvulsant' action with cholinergic drugs, as arachidonic acid and its eicosanoid metabolites can increase neuronal excitability and seizure propagation. JF - Journal of neurochemistry AU - Basselin, Mireille AU - Chang, Lisa AU - Seemann, Ruth AU - Bell, Jane M AU - Rapoport, Stanley I AD - Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. mirvasln@mail.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 1553 EP - 1562 VL - 85 IS - 6 SN - 0022-3042, 0022-3042 KW - Carbon Radioisotopes KW - 0 KW - Cholinergic Agonists KW - Arachidonic Acid KW - 27YG812J1I KW - Arecoline KW - 4ALN5933BH KW - Lithium Chloride KW - G4962QA067 KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Drug Administration Schedule KW - Wakefulness -- physiology KW - Seizures -- prevention & control KW - Arecoline -- administration & dosage KW - Autoradiography KW - Drug Administration Routes KW - Rats KW - Rats, Inbred F344 KW - Time KW - Rest -- physiology KW - Body Weight -- drug effects KW - Male KW - Lithium Chloride -- administration & dosage KW - Arachidonic Acid -- physiology KW - Signal Transduction -- physiology KW - Brain -- drug effects KW - Arachidonic Acid -- pharmacokinetics KW - Signal Transduction -- drug effects KW - Brain -- metabolism KW - Arachidonic Acid -- administration & dosage KW - Cholinergic Agonists -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73334869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chronic+lithium+administration+potentiates+brain+arachidonic+acid+signaling+at+rest+and+during+cholinergic+activation+in+awake+rats.&rft.au=Basselin%2C+Mireille%3BChang%2C+Lisa%3BSeemann%2C+Ruth%3BBell%2C+Jane+M%3BRapoport%2C+Stanley+I&rft.aulast=Basselin&rft.aufirst=Mireille&rft.date=2003-06-01&rft.volume=85&rft.issue=6&rft.spage=1553&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-10 N1 - Date created - 2003-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of antioxidative and antiapoptotic thioredoxin supports neuroprotective hypothesis of estrogen. AN - 73333800; 12777700 AB - The original neuroprotective hypothesis of estrogen was based on the gender difference in brain response to the ischemia-reperfusion injury. Additional clinical reports also suggest that estrogen may improve cognition in patients with Alzheimer disease. 17beta-Estradiol is the most potent endogenous ligand of estrogen, which protects against neurodegeneration in both cell and animal models. Estrogen-mediated neuroprotection is probably mediated by both receptor-dependent and -independent mechanisms. Binding of estrogen such as 17beta-estradiol to estrogen receptors (ERs) activates the homodimers of ER-DNA and its binding to estrogen response elements in the promoter region of genes such as neuronal nitric oxide synthase (NOS1) for regulating gene expression in target brain cells. In addition to the induction of NOS1, estrogen increases the expression of antiapoptotic protein such as bcl-2. Furthermore, our recent observations provide new molecular biologic and pharmacologic evidence suggesting that physiologic concentrations of 17beta-estradiol ( ERalpha) and upregulate a cyclic guanosine 5'- monophosphate (cGMP)-dependent thioredoxin (Trx) and MnSOD expression following the induction of NOS1 in human brain-derived SH-SY5Y cells. We thus proposed that the estrogen-mediated gene induction of Trx plays a pivotal role in the promotion of neuroprotection because Trx is a multifunctional antioxidative and antiapoptotic protein. For managing progressive neurodegeneration such as Alzheimer dementia, our estrogen proposal of the signaling pathway of cGMP-dependent protein kinase (PKG) in mediating estrogen-induced cytoprotective genes thus fosters research and development of the new estrogen ligands devoid of female hormonal side effects such as carcinogenesis. JF - Endocrine AU - Chiueh, Chuang AU - Lee, Sang AU - Andoh, Tsugunobu AU - Murphy, Dennis AD - Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. chiueh@helix.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 27 EP - 31 VL - 21 IS - 1 SN - 1355-008X, 1355-008X KW - Antioxidants KW - 0 KW - Estrogens KW - Neuroprotective Agents KW - Receptors, Estrogen KW - Thioredoxins KW - 52500-60-4 KW - Index Medicus KW - Animals KW - Receptors, Estrogen -- drug effects KW - Humans KW - Female KW - Estrogens -- pharmacology KW - Antioxidants -- pharmacology KW - Apoptosis -- drug effects KW - Thioredoxins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73333800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Induction+of+antioxidative+and+antiapoptotic+thioredoxin+supports+neuroprotective+hypothesis+of+estrogen.&rft.au=Chiueh%2C+Chuang%3BLee%2C+Sang%3BAndoh%2C+Tsugunobu%3BMurphy%2C+Dennis&rft.aulast=Chiueh&rft.aufirst=Chuang&rft.date=2003-06-01&rft.volume=21&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Endocrine&rft.issn=1355008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-20 N1 - Date created - 2003-06-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular and cellular biology of moderate-dose (1-10 Gy) radiation and potential mechanisms of radiation protection: report of a workshop at Bethesda, Maryland, December 17-18, 2001. AN - 73320524; 12751965 AB - Exposures to doses of radiation of 1-10 Gy, defined in this workshop as moderate-dose radiation, may occur during the course of radiation therapy or as the result of radiation accidents or nuclear/radiological terrorism alone or in conjunction with bioterrorism. The resulting radiation injuries would be due to a series of molecular, cellular, tissue and whole-animal processes. To address the status of research on these issues, a broad-based workshop was convened. The specific recommendations were: (1) RESEARCH: Identify the key molecular, cellular and tissue pathways that lead from the initial molecular lesions to immediate and delayed injury. The latter is a chronic progressive process for which postexposure treatment may be possible. (2) Technology: Develop high-throughput technology for studying gene, protein and other biochemical expression after radiation exposure, and cytogenetic markers of radiation exposure employing rapid and accurate techniques for analyzing multiple samples. (3) Treatment strategies: Identify additional biological targets and develop effective treatments for radiation injury. (4) Ensuring sufficient expertise: Recruit and train investigators from such fields as radiation biology, cancer biology, molecular biology, cellular biology and wound healing, and encourage collaboration on interdisciplinary research on the mechanisms and treatment of radiation injury. Communicate knowledge of the effects of radiation exposure to the general public and to investigators, policy makers and agencies involved in response to nuclear accidents/events and protection/treatment of the general public. JF - Radiation research AU - Coleman, C Norman AU - Blakely, William F AU - Fike, John R AU - MacVittie, Thomas J AU - Metting, Noelle F AU - Mitchell, James B AU - Moulder, John E AU - Preston, R Julian AU - Seed, Thomas M AU - Stone, Helen B AU - Tofilon, Philip J AU - Wong, Rosemary S L AD - Radiation Oncology Sciences Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. ccoleman@mail.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 812 EP - 834 VL - 159 IS - 6 SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - Non-programmatic KW - Radiation Dosage KW - Animals KW - Radiometry KW - DNA Damage KW - Chromosome Aberrations -- radiation effects KW - Humans KW - Whole-Body Irradiation -- adverse effects KW - Oxidative Stress KW - Radiation Injuries -- therapy KW - Mutation KW - Radiotherapy -- adverse effects KW - Radiation Protection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73320524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+and+cellular+biology+of+moderate-dose+%281-10+Gy%29+radiation+and+potential+mechanisms+of+radiation+protection%3A+report+of+a+workshop+at+Bethesda%2C+Maryland%2C+December+17-18%2C+2001.&rft.au=Coleman%2C+C+Norman%3BBlakely%2C+William+F%3BFike%2C+John+R%3BMacVittie%2C+Thomas+J%3BMetting%2C+Noelle+F%3BMitchell%2C+James+B%3BMoulder%2C+John+E%3BPreston%2C+R+Julian%3BSeed%2C+Thomas+M%3BStone%2C+Helen+B%3BTofilon%2C+Philip+J%3BWong%2C+Rosemary+S+L&rft.aulast=Coleman&rft.aufirst=C&rft.date=2003-06-01&rft.volume=159&rft.issue=6&rft.spage=812&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 - 2003-07-02 N1 - Date created - 2003-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular origins for the dominant negative function of human glucocorticoid receptor beta. AN - 73320276; 12773573 AB - This study molecularly elucidates the basis for the dominant negative mechanism of the glucocorticoid receptor (GR) isoform hGRbeta, whose overexpression is associated with human glucocorticoid resistance. Using a series of truncated hGRalpha mutants and sequential mutagenesis to generate a series of hGRalpha/beta hybrids, we find that the absence of helix 12 is neither necessary nor sufficient for the GR dominant negative phenotype. Moreover, we have localized the dominant negative activity of hGRbeta to two residues and found that nuclear localization, in addition to heterodimerization, is a critical feature of the dominant negative activity. Molecular modeling of wild-type and mutant hGRalpha and hGRbeta provides structural insight and a potential physical explanation for the lack of hormone binding and the dominant negative actions of hGRbeta. JF - Molecular and cellular biology AU - Yudt, Matthew R AU - Jewell, Christine M AU - Bienstock, Rachelle J AU - Cidlowski, John A AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 4319 EP - 4330 VL - 23 IS - 12 SN - 0270-7306, 0270-7306 KW - Ligands KW - 0 KW - Protein Isoforms KW - Receptors, Glucocorticoid KW - glucocorticoid receptor alpha KW - glucocorticoid receptor beta KW - DNA KW - 9007-49-2 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Animals KW - COS Cells KW - Cell Nucleus -- metabolism KW - Humans KW - Algorithms KW - Drug Resistance KW - Phenotype KW - Genes, Dominant KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Plasmids -- metabolism KW - Models, Molecular KW - Dimerization KW - DNA -- metabolism KW - Glutathione Transferase -- metabolism KW - Amino Acid Sequence KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Protein Binding KW - Transcriptional Activation KW - Blotting, Western KW - Transfection KW - Crystallography, X-Ray KW - Protein Structure, Tertiary KW - Immunohistochemistry KW - Mutation KW - Cell Line KW - Receptors, Glucocorticoid -- physiology KW - Receptors, Glucocorticoid -- metabolism KW - Receptors, Glucocorticoid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73320276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+origins+for+the+dominant+negative+function+of+human+glucocorticoid+receptor+beta.&rft.au=Yudt%2C+Matthew+R%3BJewell%2C+Christine+M%3BBienstock%2C+Rachelle+J%3BCidlowski%2C+John+A&rft.aulast=Yudt&rft.aufirst=Matthew&rft.date=2003-06-01&rft.volume=23&rft.issue=12&rft.spage=4319&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 - 2003-07-03 N1 - Date created - 2003-05-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Endocrinol. 1999 Nov;13(11):1855-63 [10551779] Comput Biol Med. 2001 Jul;31(4):259-67 [11334635] Bioinformatics. 1999 Nov;15(11):937-46 [10743560] Gastroenterology. 2000 May;118(5):859-66 [10784585] Exp Cell Res. 2000 Apr 10;256(1):213-24 [10739668] J Allergy Clin Immunol. 2000 May;105(5):943-50 [10808175] Annu Rev Biophys Biomol Struct. 2001;30:329-59 [11340063] Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6865-70 [11381138] Cell. 2002 Jul 12;110(1):93-105 [12151000] Science. 1985 May 10;228(4700):740-2 [2581314] Nature. 1985 Dec 19-1986 Jan 1;318(6047):635-41 [2867473] EMBO J. 1987 Nov;6(11):3333-40 [3123217] J Mol Biol. 1987 Dec 5;198(3):425-43 [3430614] Nature. 1989 Jun 22;339(6226):593-7 [2733791] J Biol Chem. 1991 Apr 15;266(11):7182-8 [1707881] J Biol Chem. 1993 Jul 5;268(19):14026-32 [8314770] J Mol Biol. 1993 Jul 20;232(2):584-99 [8345525] J Biol Chem. 1993 Oct 5;268(28):20870-6 [8407919] Protein Eng. 1994 Feb;7(2):157-64 [8170919] J Clin Invest. 1995 Jun;95(6):2435-41 [7769088] Genes Dev. 1995 Jul 1;9(13):1608-21 [7628695] J Biol Chem. 1995 Dec 29;270(52):31163-71 [8537380] Nat Struct Biol. 1996 Jan;3(1):87-94 [8548460] J Biol Chem. 1996 Apr 19;271(16):9550-9 [8621628] Proc Natl Acad Sci U S A. 1996 May 14;93(10):4948-52 [8643509] Methods Enzymol. 1996;266:383-402 [8743695] Methods Enzymol. 1996;266:540-53 [8743705] J Neuroendocrinol. 1996 Jun;8(6):405-15 [8809670] Mol Endocrinol. 1996 Jan;10(1):24-34 [8838142] Protein Sci. 1996 Nov;5(11):2298-310 [8931148] Proteins. 1997 Mar;27(3):329-35 [9094735] J Exp Med. 1997 Nov 3;186(9):1567-74 [9348314] Mol Endocrinol. 1998 Jan;12(1):45-56 [9440809] Nature. 1998 May 28;393(6683):392-6 [9620806] Biochem Biophys Res Commun. 1999 Jan 27;254(3):559-65 [9920778] Mol Cell Biol. 1999 May;19(5):3372-82 [10207061] Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1600-4 [10228133] Bioinformatics. 1999 May;15(5):413-21 [10366661] J Biol Chem. 1999 Sep 24;274(39):27857-66 [10488132] J Mol Biol. 1999 Sep 17;292(2):195-202 [10493868] Annu Rev Biochem. 1999;68:559-81 [10872460] Mol Endocrinol. 2000 Jul;14(7):1028-37 [10894152] Trends Pharmacol Sci. 2000 Oct;21(10):381-8 [11050318] Mol Cell Biol. 2001 Feb;21(3):781-93 [11154266] J Exp Med. 2001 Mar 5;193(5):585-93 [11238589] Mol Cell Biol. 2001 Apr;21(8):2838-46 [11283262] Nature. 1999 Dec 23-30;402(6764):880-3 [10622252] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. AN - 73312414; 12767102 AB - Doxorubicin is a highly effective and widely used cytotoxic agent with application that is limited by cardiotoxicity related to the cumulative dose of the drug. A large-scale study that retrospectively evaluated the cardiotoxicity of doxorubicin reported that an estimated 7% of patients developed doxorubicin-related congestive heart failure (CHF) after a cumulative dose of 550 mg/m(2). To assess whether this estimate is reflective of the incidence in the broader clinical oncology setting, the authors evaluated data from three prospective studies to determine both the incidence of doxorubicin-related CHF and the accumulated dose of doxorubicin at which CHF occurs. A group of 630 patients who were randomized to a doxorubicin-plus-placebo arm of three Phase III studies, two studies in patients with breast carcinoma and one study in patients with small cell lung carcinoma, were included in the analysis. Thirty-two of 630 patients had a diagnosis of CHF. Analysis indicated that an estimated cumulative 26% of patients would experience doxorubicin-related CHF at a cumulative dose of 550 mg/m(2). Age appeared to be an important risk factor for doxorubicin-related CHF after a cumulative dose of 400 mg/m(2), with older patients (age > 65 years) showing a greater incidence of CHF compared with younger patients (age 50% of the patients who experienced doxorubicin-related CHF had a reduction < 30% in left ventricular ejection fraction (LVEF) while they were on study. Doxorubicin-related CHF occurs with greater frequency and at a lower cumulative dose than previously reported. These findings further indicate that LVEF is not an accurate predictor of CHF in patients who receive doxorubicin. Copyright 2003 American Cancer Society. JF - Cancer AU - Swain, Sandra M AU - Whaley, Fredrick S AU - Ewer, Michael S AD - National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20889, USA. swains@mail.nih.gov Y1 - 2003/06/01/ PY - 2003 DA - 2003 Jun 01 SP - 2869 EP - 2879 VL - 97 IS - 11 SN - 0008-543X, 0008-543X KW - Antineoplastic Agents KW - 0 KW - Doxorubicin KW - 80168379AG KW - Abridged Index Medicus KW - Index Medicus KW - Ventricular Function, Left -- drug effects KW - Age Factors KW - Aged, 80 and over KW - Humans KW - Adult KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Stroke Volume -- drug effects KW - Male KW - Female KW - Doxorubicin -- adverse effects KW - Heart Failure -- chemically induced KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73312414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Congestive+heart+failure+in+patients+treated+with+doxorubicin%3A+a+retrospective+analysis+of+three+trials.&rft.au=Swain%2C+Sandra+M%3BWhaley%2C+Fredrick+S%3BEwer%2C+Michael+S&rft.aulast=Swain&rft.aufirst=Sandra&rft.date=2003-06-01&rft.volume=97&rft.issue=11&rft.spage=2869&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-20 N1 - Date created - 2003-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conditionally immortalized cell line of inducible metanephric mesenchyme. AN - 73311681; 12753294 AB - The mesenchymal-epithelial conversion of metanephric mesenchyme (MM) in the formation of nephronic tubules has long served as a paradigm for inductive signaling in morphogenesis. However, the mechanisms underlying this differentiation have remained an enigma due to insufficient numbers of primary mesenchymal cells that must be isolated manually from animal embryos. To overcome this problem, we have established a conditionally immortalized cell line, the rat-inducible metanephric mesenchyme (RIMM-18) by transfection of primary mesenchymal cells with a vector, encoding an estradiol-dependent E1A-ER fusion protein. Reverse transcription-polymerase chain reaction (RT-PCR), luciferase reporter assay, electrophoretic mobility shift assay, immunocytochemical, and immunohistochemical stainings were used to characterize the established cell line. We demonstrate that in the presence of estradiol, the RIMM-18 cell line proliferates continuously, maintaining mesenchymal characteristics for over 40 passages. These cells are vimentin-positive and cytokeratin-negative. Under inductive conditions in the absence of estradiol, they are responsive to a number of cytokines, which are established inducers of mesenchymal cells in vivo and in vitro [i.e., fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF), and transforming growth factor-beta 2 (TGF-beta 2)]. We show the presence in RIMM-18 cells of specific protein markers and functionally active signaling pathways required for induction of tubule formation in MM. Furthermore, induced RIMM-18 cells change morphology, acquiring epithelial-like features, and begin to express epithelial markers (e.g., E-cadherin, cytokeratin, gamma-glutamyl-transpeptidase, and secreted frizzled-related protein 2 (sFRP2). This preliminary characterization of the RIMM-18 cell line suggests that it will be useful in the study of biochemical and molecular mechanisms of nephronic development and, possibly, of some types of renal cancer such as Wilms' tumor, which caricatures the normal process of kidney development. JF - Kidney international AU - Levashova, Zoia B AU - Plisov, Sergei Y AU - Perantoni, Alan O AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702-1201, USA. levashovaz@ncifcfr.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 2075 EP - 2087 VL - 63 IS - 6 SN - 0085-2538, 0085-2538 KW - Biomarkers KW - 0 KW - DNA-Binding Proteins KW - Lymphoid Enhancer-Binding Factor 1 KW - Madh4 protein, rat KW - SMAD4 protein, human KW - STAT3 Transcription Factor KW - STAT3 protein, human KW - Smad4 Protein KW - Trans-Activators KW - Transcription Factors KW - Index Medicus KW - Epithelial Cells -- cytology KW - Trans-Activators -- genetics KW - Humans KW - Gene Expression KW - DNA-Binding Proteins -- genetics KW - Cell Differentiation KW - Transcription, Genetic KW - Transcription Factors -- genetics KW - Signal Transduction KW - Cell Line, Transformed -- cytology KW - Kidney -- embryology KW - Kidney -- cytology KW - Cell Line, Transformed -- physiology KW - Mesoderm -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73311681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Conditionally+immortalized+cell+line+of+inducible+metanephric+mesenchyme.&rft.au=Levashova%2C+Zoia+B%3BPlisov%2C+Sergei+Y%3BPerantoni%2C+Alan+O&rft.aulast=Levashova&rft.aufirst=Zoia&rft.date=2003-06-01&rft.volume=63&rft.issue=6&rft.spage=2075&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 - 2004-01-13 N1 - Date created - 2003-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tomato and garlic can modulate azoxymethane-induced colon carcinogenesis in rats. AN - 73305917; 12771557 AB - Tomato (Lycopersicon esculentum) and garlic (Allium cepa) are important constituents of the human diet. Compounds like diallyl sulfides, diallyl disulfides and quercetin, which are active components of garlic, have known anti-inflammatory, antimutagenic activities. Similarly, active components in tomato, such as kaempferol and chlorogenic acid, have antimutagenic activities and lycopene is the most active oxygen quencher with potential chemopreventive activities. In view of this, an endeavour was made to evaluate the anticarcinogenic effect, if any, of tomato and garlic consumption individually and in combination on azoxymethane-induced colonic precancerous lesion, the aberrant crypt foci in animal model. Sprague-Dawley rats (4-5 weeks old) were injected with azoxymethane (15 mg/kg b.w.) and orally administered with 2% (w/v) of tomato, garlic and a combination of both. After 12 weeks of first azoxymethane injection, colons were assessed for aberrant crypt foci and compared with the carcinogen control group. Lipid peroxidation level and glutathione-S-transferase (GST) activity were assessed in liver as well as in colon. Furthermore, in situ cell proliferation and apoptosis were estimated using the Brdu incorporation method and TUNEL method respectively. It was observed that aberrant crypt foci were reduced in all treated groups (by 32.11% in garlic, by 76.14% in tomato and by 55.96% in the combination group). Among treated groups, GST activity was found to be induced in both liver and colon, whereas considerable reduction in lipid peroxidation level was observed in liver as well as in colon with respect to the carcinogen control group. Significant reduction in Brdu labelling index and increase in apoptotic index in colon was noted in the treated groups. These results suggest that tomato and garlic suspensions have a protective effect on colon carcinogenesis, which is mediated by modulation of different biological pathways during carcinogenesis. JF - European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) AU - Sengupta, A AU - Ghosh, S AU - Das, S AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute 37, Kolkata, India. archanadi1@rediffmail.com Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 195 EP - 200 VL - 12 IS - 3 SN - 0959-8278, 0959-8278 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Azoxymethane KW - MO0N1J0SEN KW - Index Medicus KW - Animals KW - Precancerous Conditions -- diet therapy KW - Onions KW - Colon -- cytology KW - Colon -- drug effects KW - Cell Division -- drug effects KW - Lipid Peroxidation -- drug effects KW - Disease Models, Animal KW - Precancerous Conditions -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Precancerous Conditions -- chemically induced KW - Colon -- metabolism KW - Apoptosis -- drug effects KW - Carcinogenicity Tests KW - Injections, Subcutaneous KW - Glutathione Transferase -- drug effects KW - Lycopersicon esculentum KW - Phytotherapy KW - Carcinogens -- administration & dosage KW - Anticarcinogenic Agents -- therapeutic use KW - Azoxymethane -- toxicity KW - Azoxymethane -- administration & dosage KW - Colonic Neoplasms -- diet therapy KW - Carcinogens -- toxicity KW - Colonic Neoplasms -- metabolism KW - Garlic KW - Colonic Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73305917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tomato+and+garlic+can+modulate+azoxymethane-induced+colon+carcinogenesis+in+rats.&rft.au=Sengupta%2C+A%3BGhosh%2C+S%3BDas%2C+S&rft.aulast=Sengupta&rft.aufirst=A&rft.date=2003-06-01&rft.volume=12&rft.issue=3&rft.spage=195&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 - 2004-02-05 N1 - Date created - 2003-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metallothionein is a potential negative regulator of apoptosis. AN - 73302722; 12700406 AB - Apoptotic resistance can either be desirable or undesirable, depending on the conditions. In cancer chemotherapy, it is critical that tumor cells are selectively and effectively killed while leaving normal cells undamaged. Since acquisition of apoptotic resistance appears to be a common occurrence during malignant transformation, elucidating the mechanisms underlying apoptotic resistance is an area of intense study. Previous studies have revealed that metallothionein (MT) can protect cells from apoptosis induced by oxidative stress and metals. In the present study, we tested the hypothesis that the presence of MT may somehow modulate apoptosis. Our results revealed a strong linear negative correlation between basal MT levels and etoposide-induced apoptosis in the human tumor cell lines PLC/PRF/5, H460, and HepG2 (r = -0.991). In HepG2 cells, 24 h pretreatment with cadmium resulted in concentration-dependent increases in MT levels and marked decreases in etoposide-induced apoptosis. Zinc pretreatment also resulted in increased MT synthesis and decreased etoposide-induced apoptosis. More importantly, induced MT levels were negatively correlated with sensitivity to etoposide-induced apoptosis (r = -0.965). These suggest that MT may play a role in regulating apoptosis and that modulating MT expression may provide a strategy for altering cellular resistance to chemotherapeutic compounds. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Shimoda, Ryuya AU - Achanzar, William E AU - Qu, Wei AU - Nagamine, Takeaki AU - Takagi, Hitoshi AU - Mori, Masatomo AU - Waalkes, Michael P AD - National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 294 EP - 300 VL - 73 IS - 2 SN - 1096-6080, 1096-6080 KW - Drug Combinations KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Etoposide KW - 6PLQ3CP4P3 KW - Metallothionein KW - 9038-94-2 KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Liver Neoplasms -- metabolism KW - Hepatocytes -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Zinc -- toxicity KW - Hepatocytes -- pathology KW - Caspases -- metabolism KW - Liver Neoplasms -- pathology KW - Carcinoma, Hepatocellular -- metabolism KW - Cell Survival -- drug effects KW - Cadmium -- toxicity KW - Carcinoma, Hepatocellular -- pathology KW - Cell Line, Tumor -- drug effects KW - Cell Line, Tumor -- metabolism KW - DNA Fragmentation KW - Lung Neoplasms -- pathology KW - Lung Neoplasms -- metabolism KW - Hepatocytes -- metabolism KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Etoposide -- toxicity KW - Metallothionein -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73302722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Metallothionein+is+a+potential+negative+regulator+of+apoptosis.&rft.au=Shimoda%2C+Ryuya%3BAchanzar%2C+William+E%3BQu%2C+Wei%3BNagamine%2C+Takeaki%3BTakagi%2C+Hitoshi%3BMori%2C+Masatomo%3BWaalkes%2C+Michael+P&rft.aulast=Shimoda&rft.aufirst=Ryuya&rft.date=2003-06-01&rft.volume=73&rft.issue=2&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-10 N1 - Date created - 2003-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of distinct and common gene expression changes after oxidative stress and gamma and ultraviolet radiation. AN - 73301279; 12766906 AB - The human genome is exposed to many different kinds of DNA-damaging agents. While most damage is detected and repaired through complex damage recognition and repair machineries, some damage has the potential to escape these mechanisms. Unrepaired DNA damage can give rise to alterations and mutations in the genome in an individual cell, which can result in malignant transformation, especially when critical genes are deregulated. In this study, we investigated gene expression changes in response to oxidative stress, gamma (gamma) radiation, and ultraviolet (UV) radiation and their potential implications in cancer development. Doses were selected for each of the three treatments, based on their ability to cause a similar G(1) checkpoint induction and slow down in early S-phase progression, as reflected by a comparable reduction in cyclin E-associated kinase activity of at least 75% in logarithmically growing human dermal diploid fibroblasts. To investigate gene expression changes, logarithmically growing dermal diploid fibroblasts were exposed to either gamma radiation (5 Gy), oxidative stress (75 microM of tert-butyl hydroperoxide (t-butyl-OOH)), or UV radiation (UVC) (7.5 J/m(2)) and RNA was harvested 6 h after treatment. Gene expression was analyzed using the NIEHS Human ToxChip 2.0 with approximately 1901 cDNA clones representing known genes and expressed sequence tags (ESTs). We were able to identify common and distinct responses in dermal diploid fibroblasts to the three different stimuli used. Within our analysis, gene expression profiles in response to gamma radiation and oxidative stress appeared to be more similar than profiles expressed after UV radiation. Interestingly, equivalent cyclin E-associated kinase activity reduction with all the three treatments was associated with greater transcriptional changes after UV radiation than after gamma radiation and oxidative stress. While samples treated with UV radiation displayed modulations of their mitogen activated protein kinase (MAPK) pathway, gamma radiation had its major influence on cell-cycle progression in S-phase and mitosis. In addition, cell cultures from different individuals displayed significant differences in their gene expression responses to DNA damage. JF - Molecular carcinogenesis AU - Heinloth, Alexandra N AU - Shackelford, Rodney E AU - Innes, Cynthia L AU - Bennett, Lee AU - Li, Leping AU - Amin, Rupesh P AU - Sieber, Stella O AU - Flores, Kristina G AU - Bushel, Pierre R AU - Paules, Richard S AD - Growth Control and Cancer Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 65 EP - 82 VL - 37 IS - 2 SN - 0899-1987, 0899-1987 KW - Cyclin E KW - 0 KW - tert-Butylhydroperoxide KW - 955VYL842B KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Genetic Variation KW - Humans KW - Oligonucleotide Array Sequence Analysis -- methods KW - G1 Phase -- radiation effects KW - DNA Damage -- genetics KW - Enzyme Activation -- radiation effects KW - Cyclin-Dependent Kinases -- drug effects KW - Adult KW - Enzyme Activation -- drug effects KW - Male KW - Cyclin-Dependent Kinases -- metabolism KW - S Phase -- drug effects KW - Cyclin-Dependent Kinases -- radiation effects KW - Reproducibility of Results KW - Dose-Response Relationship, Radiation KW - Reverse Transcriptase Polymerase Chain Reaction -- methods KW - S Phase -- radiation effects KW - Gene Expression Profiling KW - Cells, Cultured KW - MAP Kinase Signaling System -- radiation effects KW - tert-Butylhydroperoxide -- pharmacology KW - G1 Phase -- drug effects KW - Cluster Analysis KW - Female KW - Fibroblasts -- drug effects KW - Gene Expression Regulation -- radiation effects KW - Gamma Rays -- adverse effects KW - Oxidative Stress KW - Ultraviolet Rays -- adverse effects KW - Gene Expression Regulation -- drug effects KW - Fibroblasts -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73301279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+distinct+and+common+gene+expression+changes+after+oxidative+stress+and+gamma+and+ultraviolet+radiation.&rft.au=Heinloth%2C+Alexandra+N%3BShackelford%2C+Rodney+E%3BInnes%2C+Cynthia+L%3BBennett%2C+Lee%3BLi%2C+Leping%3BAmin%2C+Rupesh+P%3BSieber%2C+Stella+O%3BFlores%2C+Kristina+G%3BBushel%2C+Pierre+R%3BPaules%2C+Richard+S&rft.aulast=Heinloth&rft.aufirst=Alexandra&rft.date=2003-06-01&rft.volume=37&rft.issue=2&rft.spage=65&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 - 2003-06-27 N1 - Date created - 2003-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) contains hypoxia response elements: relevance to lytic induction by hypoxia. AN - 73299198; 12767996 AB - Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), also known as human herpesvirus 8, is an etiologic agent of KS, primary effusion lymphoma (PEL), and multicentric Castleman's disease. We recently demonstrated that hypoxia can induce lytic replication of KSHV in PEL cell lines. Hypoxia induces the accumulation of hypoxia-inducible factors (HIF), and we hypothesized that the KSHV genome may respond to hypoxia through functional hypoxia response elements (HREs). Here, we demonstrate the presence of at least two promoters within the KSHV genome that are activated by hypoxia or hypoxia mimics. One is in the promoter region of the gene for Rta, the main lytic switch gene, and the other is within the promoter region of ORF34, a lytic gene of unknown function. The ORF34 promoter contains three putative consensus HREs oriented in the direction of the gene. Dissection and site-directed mutagenesis studies confirmed that one of the HREs of the ORF34 promoter is functional. Under conditions of hypoxia, the ORF34 promoter was strongly upregulated by HIF-1 alpha and HIF-2 alpha. By contrast, the promoter of the gene for Rta appeared to be preferentially upregulated by HIF-2 alpha. Reverse transcription-PCR analysis revealed that specific messages for ORF34 and ORF50 are upregulated in BCBL-1 cells exposed to hypoxia. An HIF-1 binding and competition assay demonstrated that the HRE sequence from the ORF34 promoter can compete for HIF-1 alpha binding to an erythropoietin HRE oligonucleotide while a mutant sequence cannot. Thus, we demonstrated that a viral gene can be activated by hypoxia through activation of a functional viral HRE. To our knowledge, this is the first example of a functional HRE in a viral promoter. JF - Journal of virology AU - Haque, Muzammel AU - Davis, David A AU - Wang, Victoria AU - Widmer, Isabelle AU - Yarchoan, Robert AD - HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1868, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 6761 EP - 6768 VL - 77 IS - 12 SN - 0022-538X, 0022-538X KW - HIF1A protein, human KW - 0 KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Mrgprf protein, rat KW - Receptors, Cell Surface KW - Transcription Factors KW - Erythropoietin KW - 11096-26-7 KW - Index Medicus KW - Receptors, Cell Surface -- metabolism KW - Mutagenesis, Site-Directed KW - Erythropoietin -- metabolism KW - Promoter Regions, Genetic KW - Transcription Factors -- metabolism KW - Humans KW - Binding, Competitive KW - Receptors, Cell Surface -- genetics KW - Transcription Factors -- genetics KW - Open Reading Frames -- physiology KW - Open Reading Frames -- genetics KW - Cell Line KW - Herpesvirus 8, Human -- genetics KW - Gene Expression Regulation, Viral KW - Herpesvirus 8, Human -- physiology KW - Response Elements -- genetics KW - Virus Activation KW - Cell Hypoxia KW - Response Elements -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73299198?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Kaposi%27s+sarcoma-associated+herpesvirus+%28human+herpesvirus+8%29+contains+hypoxia+response+elements%3A+relevance+to+lytic+induction+by+hypoxia.&rft.au=Haque%2C+Muzammel%3BDavis%2C+David+A%3BWang%2C+Victoria%3BWidmer%2C+Isabelle%3BYarchoan%2C+Robert&rft.aulast=Haque&rft.aufirst=Muzammel&rft.date=2003-06-01&rft.volume=77&rft.issue=12&rft.spage=6761&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-03 N1 - Date created - 2003-05-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1996 Jul 26;271(30):17771-8 [8663540] J Virol. 1996 Jan;70(1):549-58 [8523568] Blood. 1996 Oct 1;88(7):2648-54 [8839859] J Biol Chem. 1996 Dec 20;271(51):32529-37 [8955077] Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14862-7 [8962146] J Virol. 1997 Jan;71(1):314-24 [8985352] Genes Dev. 1997 Jan 1;11(1):72-82 [9000051] Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4273-8 [9113979] J Biol Chem. 1997 Sep 5;272(36):22642-7 [9278421] J Gen Virol. 1997 Sep;78 ( Pt 9):2171-8 [9292004] J Virol. 1998 Feb;72(2):1005-12 [9444993] Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7987-92 [9653127] Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10866-71 [9724796] Blood. 1998 Oct 1;92(7):2260-8 [9746763] Virology. 1998 Dec 20;252(2):304-12 [9878608] J Gen Virol. 1999 Jan;80 ( Pt 1):83-90 [9934688] J Virol. 1999 Jun;73(6):4786-93 [10233939] J Biol Chem. 1999 Aug 20;274(34):24142-6 [10446187] J Biol Chem. 1999 Aug 20;274(34):24147-52 [10446188] J Virol. 1999 Nov;73(11):9348-61 [10516043] J Virol. 2000 Mar;74(6):2867-75 [10684303] J Virol. 2000 Jul;74(13):6207-12 [10846108] Cancer Res. 2000 Sep 1;60(17):4873-80 [10987301] J Gen Virol. 2000 Dec;81(Pt 12):3043-8 [11086135] J Virol. 2001 Jan;75(2):891-902 [11134302] Endocrinology. 2001 Feb;142(2):959-62 [11159870] J Biol Chem. 2001 Jan 19;276(3):2292-8 [11056166] J Virol. 2001 May;75(10):4843-53 [11312356] Blood. 2001 May 15;97(10):3244-50 [11342455] J Virol. 2001 Aug;75(15):6894-900 [11435569] N Engl J Med. 2002 Apr 18;346(16):1207-10 [11961149] Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 [3045756] Mol Cell Biol. 1992 Dec;12(12):5447-54 [1448077] Proc Natl Acad Sci U S A. 1993 May 1;90(9):3928-32 [8387202] Science. 1994 Dec 16;266(5192):1865-9 [7997879] N Engl J Med. 1995 May 4;332(18):1186-91 [7700311] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4 [7539918] Blood. 1995 Aug 15;86(4):1276-80 [7632932] Nat Med. 1995 Jul;1(7):707-8 [7585156] Mol Cell Biol. 1996 Sep;16(9):4604-13 [8756616] N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Workshop overview: use of genomic data in risk assessment. AN - 73298547; 12700425 AB - The completion of the Human Genome Project has provided the foundation to analyze the expression of all genes transcribed in a specific cell, as well as a reference against which to assess genetic variability and its impact on susceptibility. Recent advances in genomic technologies have set the stage for better understanding and predicting individual adaptive and toxicological responses after toxicant exposure. Thus, it is now possible to simultaneously assess expression levels for thousands of different genes using DNA microarrays, as well as assess posttranscriptional and posttranslational events using high throughput proteomics. Similarly, the risk of toxicant exposure-induced disease used to be estimated across populations with widely varying responses. However, new high-throughput genomic technologies have the potential to greatly improve the accuracy of risk assessment, allowing identification of sensitive subpopulations at risk and ultimately leading to personalized risk profiles based on genetic composition. Recognizing the importance these technologies will have on the practice of risk assessment and the development of regulatory guidelines, the Society of Toxicology sponsored a workshop to evaluate the current status of genomic research; the ethical, legal, and social issues associated with these approaches; and, in this context, how data derived from these technologies would impact risk assessment. This article summarizes the evaluation by experts in genomic research and risk assessment in the first workshop to provide a forum for interaction between these scientific disciplines. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Cunningham, Michael L AU - Bogdanffy, Matthew S AU - Zacharewski, Timothy R AU - Hines, Ronald N Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 209 EP - 215 VL - 73 IS - 2 KW - Index Medicus KW - Animals KW - Humans KW - Human Genome Project KW - Toxicology -- trends KW - Genomics -- education KW - Risk Assessment -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73298547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Workshop+overview%3A+use+of+genomic+data+in+risk+assessment.&rft.au=Cunningham%2C+Michael+L%3BBogdanffy%2C+Matthew+S%3BZacharewski%2C+Timothy+R%3BHines%2C+Ronald+N&rft.aulast=Cunningham&rft.aufirst=Michael&rft.date=2003-06-01&rft.volume=73&rft.issue=2&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-10 N1 - Date created - 2003-05-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Toxicol Sci. 2003 Jun;73(2):207-8 [12700407] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A-kinase anchoring protein 4 binding proteins in the fibrous sheath of the sperm flagellum. AN - 73294009; 12606363 AB - The fibrous sheath is a unique cytoskeletal structure located in the principal piece of the sperm flagellum and is constructed of two longitudinal columns connected by closely spaced circumferential ribs. Cyclic AMP-dependent protein kinases are secured within specific cytoplasmic domains by A-kinase anchoring proteins (AKAPs), and the most abundant protein in the fibrous sheath is AKAP4. Several other fibrous sheath proteins have been identified, but how the fibrous sheath assembles is not understood. Yeast two-hybrid assays and deletion mutagenesis were used to identify AKAP4-binding proteins and to map the binding regions on AKAP4 and on the proteins identified. We found that AKAP4 binds AKAP3 and two novel spermatogenic cell-specific proteins, Fibrous Sheath Interacting Proteins 1 and 2 (FSIP1, FSIP2). Transcription of Akap4, Akap3, and Fsip1 begins in early spermatid development, whereas transcription of Fsip2 begins in late spermatocyte development. AKAP3 is synthesized in round spermatids and incorporated into the fibrous sheath concurrently with formation of the rib precursors. However, AKAP4 is synthesized and incorporated into the nascent fibrous sheath late in spermatid development. The AKAP4 precursor is processed in the flagellum and only the mature form of AKAP4 appears to bind AKAP3. These results suggest that AKAP3 is involved in organizing the basic structure of the fibrous sheath, whereas AKAP4 has a major role in completing fibrous sheath assembly. JF - Biology of reproduction AU - Brown, Paula R AU - Miki, Kiyoshi AU - Harper, Deborah B AU - Eddy, Edward M AD - Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 2241 EP - 2248 VL - 68 IS - 6 SN - 0006-3363, 0006-3363 KW - Carrier Proteins KW - 0 KW - DNA, Complementary KW - FSIP1 protein, mouse KW - Fsip2 protein, mouse KW - Seminal Plasma Proteins KW - Index Medicus KW - Animals KW - Blotting, Northern KW - DNA, Complementary -- genetics KW - Cytoskeleton -- metabolism KW - Mice KW - Protein Binding KW - Cloning, Molecular KW - Blotting, Western KW - Saccharomyces cerevisiae -- metabolism KW - Genetic Vectors KW - Immunohistochemistry KW - DNA, Complementary -- biosynthesis KW - Male KW - Gene Library KW - Seminal Plasma Proteins -- metabolism KW - Seminal Plasma Proteins -- chemistry KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- chemistry KW - Sperm Tail -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73294009?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+reproduction&rft.atitle=A-kinase+anchoring+protein+4+binding+proteins+in+the+fibrous+sheath+of+the+sperm+flagellum.&rft.au=Brown%2C+Paula+R%3BMiki%2C+Kiyoshi%3BHarper%2C+Deborah+B%3BEddy%2C+Edward+M&rft.aulast=Brown&rft.aufirst=Paula&rft.date=2003-06-01&rft.volume=68&rft.issue=6&rft.spage=2241&rft.isbn=&rft.btitle=&rft.title=Biology+of+reproduction&rft.issn=00063363&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-02 N1 - Date created - 2003-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maternally administered dexamethasone transiently increases apoptosis in lungs of fetal rats. AN - 73292829; 12746047 AB - In late gestation, morphological maturation of fetal lung includes septal thinning of potential airspaces, a process accelerated by exogenous glucocorticoids. Apoptosis occurs in normal fetal lung. Glucocorticoids increase apoptosis in several tissues. The authors hypothesized that exogenous glucocorticoids would increase apoptosis in fetal lung, primarily in the interstitium. They administered dexamethasone (DEX), 1 mg/kg, or vehicle (Control) to pregnant rats at 19 days of gestation. Fetuses were delivered at 3, 7, 12, or 24 hours post injection. DEX decreased fetal body weight and lung weight, DNA, and protein 12 hours post injection. Using the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) reaction to label apoptotic cells in lung, they calculated an apoptotic index (AI, apoptotic cells/1000 total cells) for each fetus. Average DEX AI (3.6+/-2.6, mean+/-SD) was greater than Control (1.7+/-0.5) (P<.02). All DEX AIs were greater than Control AIs at 3, 7, and 12 hours, but were similar to Controls at 24 hours post injection. Apoptotic cells appeared to be interstitial, based on colocalization with vimentin staining. Presence of apoptotic cells was confirmed by electron microscopy and detection of the nucleosomal ladder pattern on DNA electrophoresis. The authors conclude that maternal administration of dexamethasone increases apoptosis in fetal lung, primarily in the interstitium. They speculate that apoptosis may contribute to morphological fetal lung maturation induced by endogenous glucocorticoids. JF - Experimental lung research AU - Scavo, Louis M AU - Newman, Valerie AU - Ertsey, Robert AU - Chapin, Cheryl J AU - Kitterman, Joseph A AD - Cardiovascular Research Institute and Department of Pediatrics, University of California, San Francisco, USA. LouisS@intra.niddk.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 211 EP - 226 VL - 29 IS - 4 SN - 0190-2148, 0190-2148 KW - Glucocorticoids KW - 0 KW - Dexamethasone KW - 7S5I7G3JQL KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Rats KW - In Situ Nick-End Labeling KW - Animals KW - Cell Count KW - Injections, Intramuscular KW - Gestational Age KW - DNA -- analysis KW - Fetal Weight -- drug effects KW - Maternal Exposure KW - Female KW - Pregnancy KW - Organ Size -- drug effects KW - Dexamethasone -- toxicity KW - Fetus -- pathology KW - Fetus -- drug effects KW - Organogenesis -- drug effects KW - Glucocorticoids -- toxicity KW - Glucocorticoids -- administration & dosage KW - Apoptosis -- drug effects KW - Lung -- drug effects KW - Dexamethasone -- administration & dosage KW - Lung -- embryology KW - Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73292829?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+lung+research&rft.atitle=Maternally+administered+dexamethasone+transiently+increases+apoptosis+in+lungs+of+fetal+rats.&rft.au=Scavo%2C+Louis+M%3BNewman%2C+Valerie%3BErtsey%2C+Robert%3BChapin%2C+Cheryl+J%3BKitterman%2C+Joseph+A&rft.aulast=Scavo&rft.aufirst=Louis&rft.date=2003-06-01&rft.volume=29&rft.issue=4&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Experimental+lung+research&rft.issn=01902148&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-10 N1 - Date created - 2003-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arachidonic acid cytotoxicity: can arachidonic acid be a physiological mediator of cell death? AN - 73282547; 12736897 AB - Arachidonic acid is a polyunsaturated fatty acid that mediates inflammation and the functioning of several organs and systems either directly or upon its conversion into eicosanoids. However, arachidonic acid is found to be cytotoxic in vitro at concentrations that overlap physiological ones. It is tempting therefore to speculate that arachidonic acid may be a physiological inducer of apoptosis and that such cytotoxic action may be another of its roles in vivo. Nevertheless its pro-inflammatory and oxidative stress-inducing features are characteristic of necrosis and pathological conditions. We hereby review the cytotoxic action of arachidonic acid, indicate the possible pathways that lead to cell death and contemplate the cytotoxic role of arachidonic acid in vivo. Copyright 2003 John Wiley & Sons, Ltd. JF - Cell biochemistry and function AU - Pompeia, Celine AU - Lima, Thais AU - Curi, Rui AD - National Institute of Deafness and other Communication Disorders, NIH, Bethesda, MD 20892-4163, USA. pompeiac@nidcd.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 97 EP - 104 VL - 21 IS - 2 SN - 0263-6484, 0263-6484 KW - Eicosanoids KW - 0 KW - Arachidonic Acid KW - 27YG812J1I KW - Index Medicus KW - Animals KW - Humans KW - Eicosanoids -- physiology KW - Cell Death -- physiology KW - Arachidonic Acid -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73282547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biochemistry+and+function&rft.atitle=Arachidonic+acid+cytotoxicity%3A+can+arachidonic+acid+be+a+physiological+mediator+of+cell+death%3F&rft.au=Pompeia%2C+Celine%3BLima%2C+Thais%3BCuri%2C+Rui&rft.aulast=Pompeia&rft.aufirst=Celine&rft.date=2003-06-01&rft.volume=21&rft.issue=2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Cell+biochemistry+and+function&rft.issn=02636484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-30 N1 - Date created - 2003-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucagon-like peptide-1 decreases endogenous amyloid-beta peptide (Abeta) levels and protects hippocampal neurons from death induced by Abeta and iron. AN - 73280599; 12749025 AB - Glucagon-like peptide-1(7-36)-amide (GLP-1) is an endogenous insulinotropic peptide that is secreted from the gastrointestinal tract in response to food. It enhances pancreatic islet beta-cell proliferation and glucose-dependent insulin secretion and lowers blood glucose and food intake in patients with type 2 diabetes mellitus. GLP-1 receptors, which are coupled to the cyclic AMP second messenger pathway, are expressed throughout the brains of rodents and humans. It was recently reported that GLP-1 and exendin-4, a naturally occurring, more stable analogue of GLP-1 that binds at the GLP-1 receptor, possess neurotrophic properties and can protect neurons against glutamate-induced apoptosis. We report here that GLP-1 can reduce the levels of amyloid-beta peptide (Abeta) in the brain in vivo and can reduce levels of amyloid precursor protein (APP) in cultured neuronal cells. Moreover, GLP-1 and exendin-4 protect cultured hippocampal neurons against death induced by Abeta and iron, an oxidative insult. Collectively, these data suggest that GLP-1 can modify APP processing and protect against oxidative injury, two actions that suggest a novel therapeutic target for intervention in Alzheimer's disease. Copyright 2003 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Perry, TracyAnn AU - Lahiri, Debomoy K AU - Sambamurti, Kumar AU - Chen, Demao AU - Mattson, Mark P AU - Egan, Josephine M AU - Greig, Nigel H AD - Section of Drug Design and Development, Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. perryt@grc.nia.nih.gov Y1 - 2003/06/01/ PY - 2003 DA - 2003 Jun 01 SP - 603 EP - 612 VL - 72 IS - 5 SN - 0360-4012, 0360-4012 KW - Amyloid beta-Peptides KW - 0 KW - Amyloid beta-Protein Precursor KW - Neuroprotective Agents KW - Peptide Fragments KW - Peptides KW - Protein Precursors KW - Venoms KW - amyloid beta-protein (1-40) KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - exenatide KW - 9P1872D4OL KW - Iron KW - E1UOL152H7 KW - Index Medicus KW - Animals KW - Fetus KW - Iron -- pharmacology KW - Amyloid beta-Peptides -- biosynthesis KW - Amyloid beta-Protein Precursor -- metabolism KW - Mice KW - Peptides -- pharmacology KW - Amyloid beta-Peptides -- drug effects KW - Peptides -- therapeutic use KW - Iron -- metabolism KW - Amyloid beta-Protein Precursor -- drug effects KW - Rats KW - Mice, Inbred Strains KW - Rats, Sprague-Dawley KW - Oxidative Stress -- physiology KW - Down-Regulation -- physiology KW - Amyloid beta-Peptides -- metabolism KW - Amyloid beta-Peptides -- pharmacology KW - Oxidative Stress -- drug effects KW - Down-Regulation -- drug effects KW - Male KW - PC12 Cells KW - Cell Death -- physiology KW - Glucagon -- therapeutic use KW - Neurons -- metabolism KW - Alzheimer Disease -- drug therapy KW - Alzheimer Disease -- physiopathology KW - Neurons -- drug effects KW - Glucagon -- pharmacology KW - Hippocampus -- metabolism KW - Cell Death -- drug effects KW - Neuroprotective Agents -- pharmacology KW - Neurons -- pathology KW - Hippocampus -- drug effects KW - Protein Precursors -- pharmacology KW - Peptide Fragments -- biosynthesis KW - Peptide Fragments -- therapeutic use KW - Peptide Fragments -- pharmacology KW - Peptide Fragments -- drug effects KW - Hippocampus -- physiopathology KW - Protein Precursors -- therapeutic use KW - Alzheimer Disease -- metabolism KW - Neuroprotective Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73280599?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glucagon-like+peptide-1+decreases+endogenous+amyloid-beta+peptide+%28Abeta%29+levels+and+protects+hippocampal+neurons+from+death+induced+by+Abeta+and+iron.&rft.au=Perry%2C+TracyAnn%3BLahiri%2C+Debomoy+K%3BSambamurti%2C+Kumar%3BChen%2C+Demao%3BMattson%2C+Mark+P%3BEgan%2C+Josephine+M%3BGreig%2C+Nigel+H&rft.aulast=Perry&rft.aufirst=TracyAnn&rft.date=2003-06-01&rft.volume=72&rft.issue=5&rft.spage=603&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 - 2003-07-16 N1 - Date created - 2003-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of 1-mo bolus subcutaneous administration of exendin-4 in type 2 diabetes. AN - 73265254; 12475750 AB - A gut insulinotropic peptide, glucagon-like peptide-1 (GLP-1), when given continuously subcutaneously, has been shown to be an effective agent to treat type 2 diabetes. Because of inactivation by dipeptidyl peptidase IV (DPP IV), it has a very short half-life (90-120 s), hence the need for continuous administration. Exendin-4 is an agonist of the GLP-1 receptor. It is not a substrate for DPP IV, and we previously demonstrated that intravenous administration has potent insulinotropic properties in type 2 diabetic volunteers. We evaluated the efficacy of bolus subcutaneous exendin-4 in insulin-naive type 2 diabetic volunteers. Ten patients aged 44-72 yr with mean fasting glucose levels of 11.4 +/- 0.9 mmol/l were enrolled, and daily or twice-daily bolus subcutaneous exendin-4 was self-administered for 1 mo. Glycosylated hemoglobin, multiple daily capillary blood glucose, beta-cell sensitivity to glucose, and peripheral tissue sensitivity to insulin were compared before and after treatment. The greatest decline in capillary blood glucose was seen before bed, with a drop from 15.5 to 9.2 mmol/l (P < 0.0001). Glycosylated hemoglobin improved significantly with treatment, from 9.1 to 8.3% (P = 0.009). beta-Cell sensitivity to glucose was improved, as assessed by C-peptide levels during a hyperglycemic clamp. No significant adverse effects were noted or reported. Our data suggest that, even with this short duration of therapy, exendin-4 treatment had a significant effect on glucose homeostasis. JF - American journal of physiology. Endocrinology and metabolism AU - Egan, Josephine M AU - Meneilly, Graydon S AU - Elahi, Dariush AD - Diabetes Section, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - E1072 EP - E1079 VL - 284 IS - 6 SN - 0193-1849, 0193-1849 KW - Blood Glucose KW - 0 KW - C-Peptide KW - Fatty Acids, Nonesterified KW - Hemoglobin A, Glycosylated KW - Hypoglycemic Agents KW - Insulin KW - Peptides KW - Venoms KW - Glucagon KW - 9007-92-5 KW - exenatide KW - 9P1872D4OL KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Blood Glucose -- metabolism KW - C-Peptide -- blood KW - Insulin -- blood KW - Humans KW - Islets of Langerhans -- drug effects KW - Aged KW - Insulin Resistance -- physiology KW - Glucose -- pharmacology KW - Hemoglobin A, Glycosylated -- metabolism KW - Glucose Clamp Technique KW - Injections, Subcutaneous KW - Middle Aged KW - Fatty Acids, Nonesterified -- blood KW - Glucagon -- blood KW - Body Composition -- drug effects KW - Male KW - Female KW - Diabetes Mellitus, Type 2 -- drug therapy KW - Hypoglycemic Agents -- therapeutic use KW - Peptides -- administration & dosage KW - Hypoglycemic Agents -- administration & dosage KW - Diabetes Mellitus, Type 2 -- blood KW - Peptides -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73265254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+physiology.+Endocrinology+and+metabolism&rft.atitle=Effects+of+1-mo+bolus+subcutaneous+administration+of+exendin-4+in+type+2+diabetes.&rft.au=Egan%2C+Josephine+M%3BMeneilly%2C+Graydon+S%3BElahi%2C+Dariush&rft.aulast=Egan&rft.aufirst=Josephine&rft.date=2003-06-01&rft.volume=284&rft.issue=6&rft.spage=E1072&rft.isbn=&rft.btitle=&rft.title=American+journal+of+physiology.+Endocrinology+and+metabolism&rft.issn=01931849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-19 N1 - Date created - 2003-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Emerging issues in gender and ethnic differences in substance abuse and treatment. AN - 73261828; 12734036 AB - The emerging understanding of gender differences among ethnic minorities in the rates, etiology, course, and treatment of substance abuse and common comorbid mental health disorders has significant scientific and practical implications. Growing recognition of these differences and their implications for treatment and policy decisions has highlighted research gaps and the need for more thoughtful application of the knowledge gained from existing research findings. In this brief review, we outline some of the unique aspects of substance abuse and comorbid mental health problems for women, as well as for women of various ethnic/cultural groups, including specific barriers to obtaining and remaining in treatment. Research challenges to improving limited knowledge about the rates, course, and treatment of substance abuse disorders among ethnic minority women are highlighted. JF - Current women's health reports AU - Weiss, Susan R B AU - Kung, Hsiang-Ching AU - Pearson, Jane L AD - National Institute on Drug Abuse, National Institutes of Health, 6001 Executive Blvd. Room 5241, MSC 9591, Bethesda, MD 20892-9591, USA. sweiss@nida.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 245 EP - 253 VL - 3 IS - 3 SN - 1534-5874, 1534-5874 KW - Index Medicus KW - United States KW - Sex Factors KW - Women's Health KW - Humans KW - Ethnic Groups -- psychology KW - Mental Health Services -- organization & administration KW - Female KW - Substance-Related Disorders -- therapy KW - Mental Disorders -- therapy KW - Acculturation KW - Mental Disorders -- ethnology KW - Substance-Related Disorders -- ethnology KW - Cultural Diversity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73261828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+women%27s+health+reports&rft.atitle=Emerging+issues+in+gender+and+ethnic+differences+in+substance+abuse+and+treatment.&rft.au=Weiss%2C+Susan+R+B%3BKung%2C+Hsiang-Ching%3BPearson%2C+Jane+L&rft.aulast=Weiss&rft.aufirst=Susan+R&rft.date=2003-06-01&rft.volume=3&rft.issue=3&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Current+women%27s+health+reports&rft.issn=15345874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-09 N1 - Date created - 2003-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Employed adolescents and beliefs about self-efficacy to avoid smoking. AN - 73261014; 12726779 AB - This paper examines self-efficacy to avoid cigarette smoking and its association with smoking and quitting behavior, peer and worksite influences, nicotine dependence, and socio-demographic variables among employed adolescents. A cross-sectional survey was used to collect data from employed adolescents ages 15-18 who worked in 10 participating grocery stores in Massachusetts. Eighty-three percent of workers (n=379) completed the survey. Results from the multivariate model indicate that daily smokers were less confident in their ability to avoid smoking than those who smoked less frequently. As nicotine dependence increased, self-efficacy beliefs decreased. In addition, as friends' encouragement to quit increased, self-efficacy beliefs also increased. Work-related variables were not associated with self-efficacy beliefs among smokers. This study suggests that smoking frequency, nicotine dependence, and friends' encouragement to quit are associated with self-efficacy to avoid smoking. Researchers may tailor interventions for daily and less-than-daily smokers, build on peer networks that encourage quitting and help smokers resist pressures to smoke, and enhance strategies for coping with nicotine dependence in high-risk situations. JF - Addictive behaviors AU - Fagan, Pebbles AU - Eisenberg, Marla AU - Frazier, Lindsay AU - Stoddard, Anne M AU - Avrunin, Jill S AU - Sorensen, Glorian AD - Dana-Farber Cancer Institute, Harvard School of Public Heath, Boston, MA, USA. faganp@mail.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 613 EP - 626 VL - 28 IS - 4 SN - 0306-4603, 0306-4603 KW - Index Medicus KW - Cross-Sectional Studies KW - Humans KW - Social Support KW - Workplace KW - Peer Group KW - Adolescent KW - Male KW - Female KW - Smoking Cessation -- psychology KW - Tobacco Use Disorder -- psychology KW - Self Efficacy KW - Smoking -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73261014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addictive+behaviors&rft.atitle=Employed+adolescents+and+beliefs+about+self-efficacy+to+avoid+smoking.&rft.au=Fagan%2C+Pebbles%3BEisenberg%2C+Marla%3BFrazier%2C+Lindsay%3BStoddard%2C+Anne+M%3BAvrunin%2C+Jill+S%3BSorensen%2C+Glorian&rft.aulast=Fagan&rft.aufirst=Pebbles&rft.date=2003-06-01&rft.volume=28&rft.issue=4&rft.spage=613&rft.isbn=&rft.btitle=&rft.title=Addictive+behaviors&rft.issn=03064603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-20 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fibroblasts from chronic wounds show altered TGF-beta-signaling and decreased TGF-beta Type II receptor expression. AN - 73214485; 12704642 AB - Chronic wounds are characterized by failure to heal in a defined time frame. However, the pathogenic steps leading from the etiological factors to failure to heal are unknown. Recently, increasing evidence suggests that resident cells in chronic wounds display a number of critical abnormalities, including senescence and unresponsiveness to the stimulatory action of transforming growth factor-beta1 (TGF-beta1). In this study, we have determined some of the mechanisms that might be responsible for unresponsiveness to TGF-beta1. Using Northern analysis and affinity labeling, we show that venous ulcer fibroblasts have decreased TGF-beta Type II receptor expression. This finding is not the result of genetic mutation, as shown by experiments with Type II receptor satellite instability. Decreased Type II receptor expression was accompanied by failure of ulcer fibroblasts to phosphorylate Smad 2, Smad 3, and p42/44 mitogen activating protein kinase (MAPK), and was associated with a slower proliferative rate in response to TGF-beta1. We conclude that venous ulcer fibroblasts show decreased Type II receptor expression and display abnormalities in the downstream signaling pathway involving MAPK and the early Smad pathway. These findings suggest ways to address and treat the abnormal cellular phenotype of cells in chronic wounds. Copyright 2003 Wiley-Liss, Inc. JF - Journal of cellular physiology AU - Kim, Byung-Chul AU - Kim, Heung Tae AU - Park, Seok Hee AU - Cha, Ji-Sun AU - Yufit, Tatyana AU - Kim, Seong-Jin AU - Falanga, Vincent AD - National Institutes of Health, National Cancer Institute, Laboratory of Cell Regulation and Carcinogenesis, Bethesda, Maryland 20892, USA. Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 331 EP - 336 VL - 195 IS - 3 SN - 0021-9541, 0021-9541 KW - Receptors, Transforming Growth Factor beta KW - 0 KW - TGFB1 protein, human KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Phosphorylation KW - Down-Regulation KW - Mitogen-Activated Protein Kinases -- metabolism KW - Cells, Cultured KW - Humans KW - Gene Expression Regulation KW - Chronic Disease KW - Transforming Growth Factor beta -- pharmacology KW - Receptors, Transforming Growth Factor beta -- genetics KW - Fibroblasts -- drug effects KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Varicose Ulcer -- metabolism KW - Varicose Ulcer -- genetics KW - Fibroblasts -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73214485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+physiology&rft.atitle=Fibroblasts+from+chronic+wounds+show+altered+TGF-beta-signaling+and+decreased+TGF-beta+Type+II+receptor+expression.&rft.au=Kim%2C+Byung-Chul%3BKim%2C+Heung+Tae%3BPark%2C+Seok+Hee%3BCha%2C+Ji-Sun%3BYufit%2C+Tatyana%3BKim%2C+Seong-Jin%3BFalanga%2C+Vincent&rft.aulast=Kim&rft.aufirst=Byung-Chul&rft.date=2003-06-01&rft.volume=195&rft.issue=3&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-27 N1 - Date created - 2003-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Resetting the immune system in immune thrombocytopenic purpura: immunoablative strategies. AN - 71611134; 16235418 AB - As is the case with many chronic disorders, the toxicity of treatment for refractory immune thrombocytopenic purpura (ITP) often rivals that of the disease itself. In recent years, attention has turned to strategies designed to permanently rectify the abnormal immune milieu that has permitted the production of autoreactive antibodies, thereby averting chronic administration of morbidity-causing immunosuppressive medications. Approaches that will be discussed include conventional chemotherapy, high-dose chemotherapy with and without autologous stem cell support, and allogeneic transplantation. JF - Clinical advances in hematology & oncology : H&O AU - Fogarty, Patrick F AU - Dunbar, Cynthia E AD - Department of Laboratory Medicine, Hematology Service, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1508, USA. fogartyp@nhlbi.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 365 EP - 371 VL - 1 IS - 6 SN - 1543-0790, 1543-0790 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Humans KW - Hematopoietic Stem Cell Transplantation KW - Antineoplastic Agents -- therapeutic use KW - Purpura, Thrombocytopenic, Idiopathic -- therapy KW - Immune System -- drug effects KW - Immune System -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71611134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+advances+in+hematology+%26+oncology+%3A+H%26O&rft.atitle=Resetting+the+immune+system+in+immune+thrombocytopenic+purpura%3A+immunoablative+strategies.&rft.au=Fogarty%2C+Patrick+F%3BDunbar%2C+Cynthia+E&rft.aulast=Fogarty&rft.aufirst=Patrick&rft.date=2003-06-01&rft.volume=1&rft.issue=6&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=Clinical+advances+in+hematology+%26+oncology+%3A+H%26O&rft.issn=15430790&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-12-13 N1 - Date created - 2005-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytokine network in inflammatory bowel disease. AN - 71278386; 14561161 AB - Disease states, such as those characterized by inflammation of the gastrointestinal tract (Crohn's disease and ulcerative colitis), are due to a host of factors that act in concert to produce pathologic change. The immunologic factors that mediate the development of such mucosal inflammation have been at the forefront of IBD research. Recently, a better understanding of the mechanisms involved in mucosal homeostasis and the occurrence of inflammatory bowel disease (IBD) has been achieved with the advent of animal models of mucosal inflammation. This review discusses these models and the insights they provide into the pathogenesis and regulation of IBD. JF - Current drug targets. Inflammation and allergy AU - Fuss, Ivan J AD - Mucosal Immunity Section, National Institutes of Health, 10 center Dr, Build 10 Rm 11N238, Bethesda, MD 20892, USA. ifuss@niaid.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 101 EP - 112 VL - 2 IS - 2 SN - 1568-010X, 1568-010X KW - Cytokines KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Colitis -- physiopathology KW - Intestinal Mucosa -- pathology KW - Disease Models, Animal KW - Colitis -- pathology KW - Colitis -- chemically induced KW - Inflammatory Bowel Diseases -- physiopathology KW - Cytokines -- physiology KW - Inflammatory Bowel Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71278386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+drug+targets.+Inflammation+and+allergy&rft.atitle=Cytokine+network+in+inflammatory+bowel+disease.&rft.au=Fuss%2C+Ivan+J&rft.aulast=Fuss&rft.aufirst=Ivan&rft.date=2003-06-01&rft.volume=2&rft.issue=2&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Current+drug+targets.+Inflammation+and+allergy&rft.issn=1568010X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-17 N1 - Date created - 2003-10-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polymorphisms in the insulin-degrading enzyme gene are associated with type 2 diabetes in men from the NHLBI Framingham Heart Study AN - 216475392; 12765971 AB - Linkage studies have mapped a susceptibility gene for type 2 diabetes to the long arm of chromosome 10, where we have previously identified a quantitative trait locus that affects fasting blood glucose within the Framingham Heart Study cohort. One candidate gene in this region is the insulin-degrading enzyme (IDE), which, in the GK rat model, has been associated with nonobese type 2 diabetes. Single nucleotide polymorphisms (SNPs) were used to map a haplotype block in the 3' end of IDE, which revealed association with HbA(1c), fasting plasma glucose (FPG), and mean fasting plasma glucose (mFPG) measured over 20 years. The strongest associations were found in a sample of unrelated men. The lowest trait values were associated with a haplotype (TT, f approximately 0.32) containing the minor allele of rs2209772 and the major allele of the rs1887922 SNP (FPG P < 0.001, mFPG P < 0.003, HbA(1c) P < 0.025). Another haplotype (CC, f approximately 0.16) was associated with elevated HbA(1c) (P < 0.002) and type 2 diabetes (P < 0.001, odds ratio 1.96, 95% CI 1.28-3.00). The evidence presented supports the possibility that IDE is a susceptibility gene for diabetes in populations of European descent. JF - Diabetes AU - Karamohamed, Samer AU - Demissie, Serkalem AU - Volcjak, Jeannine AU - Liu, Chunyu AU - et al Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 1562 EP - 7 CY - New York PB - American Diabetes Association VL - 52 IS - 6 SN - 00121797 KW - Medical Sciences--Endocrinology KW - Blood Glucose KW - Insulysin KW - Regression Analysis KW - Diabetes Mellitus, Type 2 -- enzymology KW - Haplotypes KW - Blood Glucose -- metabolism KW - Sex Characteristics KW - Humans KW - Cohort Studies KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Middle Aged KW - Chromosome Mapping KW - Male KW - Female KW - Polymorphism, Genetic KW - Insulysin -- genetics KW - Chromosomes, Human, Pair 10 KW - Diabetes Mellitus, Type 2 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/216475392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes&rft.atitle=Polymorphisms+in+the+insulin-degrading+enzyme+gene+are+associated+with+type+2+diabetes+in+men+from+the+NHLBI+Framingham+Heart+Study&rft.au=Karamohamed%2C+Samer%3BDemissie%2C+Serkalem%3BVolcjak%2C+Jeannine%3BLiu%2C+Chunyu%3Bet+al&rft.aulast=Karamohamed&rft.aufirst=Samer&rft.date=2003-06-01&rft.volume=52&rft.issue=6&rft.spage=1562&rft.isbn=&rft.btitle=&rft.title=Diabetes&rft.issn=00121797&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Diabetes Association Jun 2003 N1 - Last updated - 2013-02-06 N1 - CODEN - DIAEAZ ER - TY - JOUR T1 - Abatement of Odor Emissions from Landfills Using Natural Effective Microorganism Enzyme AN - 19977850; 6756485 AB - Concentrations of ammonia (NH sub(3)), hydrogen sulfide (H sub(2)S) and methyl mercaptan (CH sub(3)SH) are high in the air above landfills in Taiwan. Odors are strong and many flies are present. These factors were studied in the air above selected landfill sites where odor was considered to be a nuisance. In this study, Natural Effective Microorganisms Enzyme (NEME) was sprayed on selected sampling sites to reduce the odor, the concentration of NH sub(3), H sub(2)S and CH sub(3)SH and the number of flies in landfills. The odor levels, the concentrations of NH sub(3), H sub(2)S and CH sub(3)SH and the numbers of flies at various sampling sites before and after spraying with NEME were discussed. Results revealed that at the Tian-Wai-Tian Landfill in Ji-Long City, after NEME was sprayed, the measured odor level ranged from 190 to 552, and the reduction ratios were 99.4%. At the Yan-Pu Country Landfill, after it was spraying with NEME, the measured odor level had a mean of 1360 and the reduction ratio had a mean of 71.6%. At the Ping-Tung Municipal Landfill, after it was sprayed with NEME, the measured odor level had a mean of 602 and the reduction ratio averaged 68.1%. The reduction ratio of NH sub(3) from landfills averaged 72.2% and 61.1% at the Yan-Pu Country Landfill and the Ping-Tung Municipal Landfill, respectively. However, both before and after spraying with NEME, the measured H sub(2)S and CH sub(3)SH concentrations at both the Yan-Pu Country Landfill and the Ping-Tung Municipal Landfill were under 0.03 ppm. The reduction ratio of the number of captured flies averaged 55.0% and 39.7% at the Yan-Pu Country Landfill and the Ping-Tung Municipal Landfill, respectively. JF - Aerosol and Air Quality Resarch AU - Chen, Shui-Jen AU - Hsieh, Lien-Te AU - Hwang, Wen-Ing AU - Xu, He-Cheng AU - Kao, Jen-Ho AD - Department of Environmental Engineering and Science, National Pingtung University of Science and Technology, Nei Pu 91207, Ping Tung, Taiwan, ROC, chensj@mail.npust.edu.tw Y1 - 2003/06// PY - 2003 DA - Jun 2003 VL - 3 IS - 1 SN - 1680-8584, 1680-8584 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Pollution Abstracts; Chemoreception Abstracts KW - Taiwan KW - Aerosols KW - Landfills KW - Ammonia KW - Enzymes KW - Emission control KW - Air quality KW - Odors KW - Hydrogen sulfide KW - Spraying KW - Waste disposal sites KW - Microorganisms KW - Odor KW - Sampling KW - Odor control KW - A 01380:Plant Protection, Fungicides & Seed Treatments KW - P 0000:AIR POLLUTION KW - R 18110:Odor control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19977850?accountid=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=Aerosol+and+Air+Quality+Resarch&rft.atitle=Abatement+of+Odor+Emissions+from+Landfills+Using+Natural+Effective+Microorganism+Enzyme&rft.au=Chen%2C+Shui-Jen%3BHsieh%2C+Lien-Te%3BHwang%2C+Wen-Ing%3BXu%2C+He-Cheng%3BKao%2C+Jen-Ho&rft.aulast=Chen&rft.aufirst=Shui-Jen&rft.date=2003-06-01&rft.volume=3&rft.issue=1&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Aerosol+and+Air+Quality+Resarch&rft.issn=16808584&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Aerosols; Landfills; Ammonia; Microorganisms; Odor; Enzymes; Sampling; Spraying; Hydrogen sulfide; Odor control; Waste disposal sites; Air quality; Emission control; Odors; Taiwan ER - TY - JOUR T1 - Timeline: The prospect for bacteriophage therapy in Western medicine AN - 19526488; 7924126 AB - Bacteriophage (phage) have been used for clinical applications since their initial discovery at the beginning of the twentieth century. JF - Nature Reviews: Drug Discovery AU - Merril, Carl R AU - Scholl, Dean AU - Adhya, Sankar L AD - Section on Biochemical Genetics, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA., merrilc@helix.nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 489 EP - 497 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 2 IS - 6 SN - 1474-1784, 1474-1784 KW - Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts KW - Phages KW - Bacteria KW - Reviews KW - Therapeutic applications KW - W 30905:Medical Applications KW - V 22310:Genetics, Taxonomy & Structure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19526488?accountid=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+Reviews%3A+Drug+Discovery&rft.atitle=Timeline%3A+The+prospect+for+bacteriophage+therapy+in+Western+medicine&rft.au=Merril%2C+Carl+R%3BScholl%2C+Dean%3BAdhya%2C+Sankar+L&rft.aulast=Merril&rft.aufirst=Carl&rft.date=2003-06-01&rft.volume=2&rft.issue=6&rft.spage=489&rft.isbn=&rft.btitle=&rft.title=Nature+Reviews%3A+Drug+Discovery&rft.issn=14741784&rft_id=info:doi/10.1038%2Fnrd1111 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-02-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Phages; Reviews; Therapeutic applications; Bacteria DO - http://dx.doi.org/10.1038/nrd1111 ER - TY - JOUR T1 - Comparative DNA Microarray Analysis of Host Cell Transcriptional Responses to Infection by Coxiella burnetii or Chlamydia trachomatis AN - 19482257; 8396772 AB - AbstractDNA microarray analysis was conducted to investigate the transcriptional responses of the human monocytic leukemia cell line THP-1 to infection by Chlamydia trachomatis or Coxiella burnetii. RNA was isolated from mock infected cells and cells infected for 36 hours using TRIzol reagent. Biotinylated probes synthesized from RNA samples were hybridized to an Affymetrix U133A human genome chip consisting of 18,462 human gene probe sets. A total of 335 and 548 THP-1 genes were up- or downregulated at least twofold in cells infected with C. burnetii or C. trachomatis, respectively, when compared to uninfected cells. There was a high degree of overlap in transcriptional responses to infection with shared responses observed for 39 downregulated and 189 upregulated genes. Numerous pathogen-specific transcriptional responses were also observed. Quantitative RT-PCR and immunoblotting confirmed up- or down-regulation of a subset of THP-1 genes in response to infection by C. burnetii. This study provides insight into the host transcriptional responses to infection by Chlamydia and Coxiella that may affect the infectious cycle of each organism. JF - Annals of the New York Academy of Sciences AU - Ren, Qun AU - Robertson, Shelly J AU - Howe, Dale AU - Barrows, Lorraine F AU - Heinzen, Robert A AD - Department of Molecular Biology, University of Wyoming, Laramie, Wyoming 82071-3944, USA, rheinzen@niaid.nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 701 EP - 713 PB - Blackwell Publishing Ltd., 9600 Garsington Road VL - 990 IS - 1 SN - 0077-8923, 0077-8923 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Coxiella KW - Chlamydia KW - DNA microarray KW - transcription KW - gene expression KW - inflammation KW - Genomes KW - Immunoblotting KW - DNA probes KW - Chlamydia trachomatis KW - Transcription KW - Infection KW - DNA microarrays KW - Coxiella burnetii KW - Tumor cell lines KW - Monocytic leukemia KW - RNA probes KW - RNA KW - Polymerase chain reaction KW - J 02310:Genetics & Taxonomy KW - W 30910:Imaging KW - N 14810:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19482257?accountid=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=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Comparative+DNA+Microarray+Analysis+of+Host+Cell+Transcriptional+Responses+to+Infection+by+Coxiella+burnetii+or+Chlamydia+trachomatis&rft.au=Ren%2C+Qun%3BRobertson%2C+Shelly+J%3BHowe%2C+Dale%3BBarrows%2C+Lorraine+F%3BHeinzen%2C+Robert+A&rft.aulast=Ren&rft.aufirst=Qun&rft.date=2003-06-01&rft.volume=990&rft.issue=1&rft.spage=701&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fj.1749-6632.2003.tb07447.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Genomes; Immunoblotting; Tumor cell lines; RNA probes; Monocytic leukemia; RNA; DNA probes; Polymerase chain reaction; Transcription; Infection; DNA microarrays; Coxiella burnetii; Chlamydia trachomatis DO - http://dx.doi.org/10.1111/j.1749-6632.2003.tb07447.x ER - TY - JOUR T1 - Peptide nucleic acids as epigenetic inhibitors of HIV-1 AN - 19465436; 7029777 AB - The advent of highly active antiretroviral therapy (HAART) was once perceived to havetransformed deadly HIV/AIDS into a treatable, chronic infectious disease. However, mountingevidence now suggests that the prevalence of multi-drug resistant HIV (MDR-HIV) infection issteadily rising among newly infected individuals in the HAART-experienced countries, raising aconcern for a future outbreak of MDR-HIV/AIDS. Our global fight against AIDS must include sustainedeffort to search and discover a new therapeutic modality for HIV infection. Of plausible viraltargets explored to date, HIV gene-targeting approach has not yet seen a considerable success invivo. The pursuit of anti-HIV gene intervention should include the identification of critical genetargets as well as the optimization of biomolecules that can effectively interact with theintended targets. Using unmodified peptide nucleic acids (PNA) as a biomolecular tool, we discovereda potentially critical HIV gene segment within gag-polencoding gene. Antisense PNA targetingthis specific region effectively disrupted a translation of HIV gag-polmRNA, abolishing thevirion production from chronically HIV-infected cells. This exemplifies the possibility that epigenic HIV inhibitors may be developed in the coming years, if emerging novel technologies permitsufficient and stable in vivo delivery of PNA or other similarly effective biomolecules. JF - International Journal of Peptide Research and Therapeutics AU - Sei, Shizuko AD - National Cancer Institute at Frederick, Bldg. 469, Rm. 105, Frederick, MD 21702, U.S.A. Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 269 EP - 286 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 10 IS - 3-4 SN - 1573-3149, 1573-3149 KW - HIV-1 KW - Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Translation KW - Acquired immune deficiency syndrome KW - Antisense KW - Infectious diseases KW - highly active antiretroviral therapy KW - epigenetics KW - Human immunodeficiency virus 1 KW - Infection KW - peptide nucleic acids KW - W 30925:Genetic Engineering KW - V 22360:AIDS and HIV KW - N 14825:Gene Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19465436?accountid=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=International+Journal+of+Peptide+Research+and+Therapeutics&rft.atitle=Peptide+nucleic+acids+as+epigenetic+inhibitors+of+HIV-1&rft.au=Sei%2C+Shizuko&rft.aulast=Sei&rft.aufirst=Shizuko&rft.date=2003-06-01&rft.volume=10&rft.issue=3-4&rft.spage=269&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Peptide+Research+and+Therapeutics&rft.issn=15733149&rft_id=info:doi/10.1007%2Fs10989-004-4925-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Translation; Antisense; Acquired immune deficiency syndrome; Infectious diseases; epigenetics; highly active antiretroviral therapy; Infection; peptide nucleic acids; Human immunodeficiency virus 1 DO - http://dx.doi.org/10.1007/s10989-004-4925-7 ER - TY - JOUR T1 - PNAs as novel cancer therapeutics AN - 19459460; 7029769 AB - Peptide nucleic acid (PNA) is a hybrid compound with nucleoside bases linked to a peptide-like amide backbone. PNA is capable of sequence-specific base pairing and forms highly stable double and triple helices with natural nucleic acids (DNA, RNA). PNA forms stable hydrogen bonds and is resistant to degradation by nucleases and proteases. Because of these physico-chemical properties, PNA has attracted great attention, since its first description in 1991, as a potential gene-specific drug and a versatile molecular biology tool. More and more laboratories are working with PNA, and the number of applications in which PNA proves useful continues to increase.In this chapter, we describe aspects of the biochemistry of peptide nucleic acids and their use as a molecular biology reagent, and then focus on the antisense and anti-gene activity of PNA, with special reference to studies of medical interest, in particular in the PML/RAR alpha and the bcl-2systems. JF - International Journal of Peptide Research and Therapeutics AU - Mologni, Luca AU - Gambacorti-Passerini, Carlo AD - National Cancer Institute, Via Venezian 1, 20133, Milan, Italy Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 297 EP - 308 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 10 IS - 3-4 SN - 1573-3149, 1573-3149 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Nucleotide sequence KW - Physicochemical properties KW - Nuclease KW - Cancer KW - peptide nucleic acids KW - Antisense KW - nucleic acids KW - RNA KW - Hydrogen bonding KW - Hybrids KW - nucleosides KW - DNA KW - Proteinase KW - amides KW - Drugs KW - N 14815:Nucleotide Sequence KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19459460?accountid=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=International+Journal+of+Peptide+Research+and+Therapeutics&rft.atitle=PNAs+as+novel+cancer+therapeutics&rft.au=Mologni%2C+Luca%3BGambacorti-Passerini%2C+Carlo&rft.aulast=Mologni&rft.aufirst=Luca&rft.date=2003-06-01&rft.volume=10&rft.issue=3-4&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Peptide+Research+and+Therapeutics&rft.issn=15733149&rft_id=info:doi/10.1007%2Fs10989-004-4909-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Nucleotide sequence; Physicochemical properties; Nuclease; Cancer; peptide nucleic acids; Antisense; nucleic acids; RNA; Hydrogen bonding; Hybrids; nucleosides; DNA; Proteinase; Drugs; amides DO - http://dx.doi.org/10.1007/s10989-004-4909-7 ER - TY - JOUR T1 - Rickettsial Actin-Based Motility AN - 19309842; 8396745 AB - AbstractActin-based motility (ABM) is employed by spotted fever group (SFG) rickettsiae, such as Rickettsia rickettsii, to promote cell-to-cell spread. Time-lapse video microscopy revealed that ABM is not strictly confined to SFG rickettsiae as typhus group R. typhi moved at approximately the same rate as R. rickettsii (approximately 4 mu m-min), but in a highly erratic fashion. A number of common behaviors were observed between ABM of R. typhi and R. rickettsii, such as entrance into plasma membrane protrusions, formation of new actin tails only on the old surface of newly formed daughter cells, and quick (within 15 sec) reassembly of the actin tail to the opposite pole upon contact with cellular structures that impede forward movement. This last behavior suggests that the rickettsial protein(s) required for ABM is uniformly localized to both poles of the bacterium and possibly throughout the rickettsial surface. Functional roles in rickettsial ABM for neuronal Wiskott-Aldrich syndrome protein (N-WASP) and the actin-related protein (Arp)2-3 complex, critical regulators of ABM of other pathogens, have not been established. Domains of N-WASP that have characterized inhibitory effects on N-WASP or Arp2-3 complex function were expressed in HeLa cells infected with R. rickettsii. Shigella flexneri-infected cells were used as a control. When ectopically expressed, the VCA domain of N-WASP (VCA) acts as a dominant-negative with respect to Arp2-3 complex function and N-WASP missing VCA ( Delta VCA) acts as a dominant-negative form of N-WASP. Expression of VCA or Delta VCA severely inhibited S. flexneri ABM (no Shigella motility observed in the majority of expressing cells) while only moderately inhibiting ABM of R. rickettsii (approximately 35% decrease in the rate of ABM). In addition, ectopically expressed full-length GFP-N-WASP was recruited by S. flexneri but not R. rickettsii, and Arp3 was detected by indirect immunofluorescence in S. flexneri actin tails but not within R. rickettsii actin tails. Collectively, these data suggest that rickettsial ABM is independent of N-WASP and Arp2-3 complex function. JF - Annals of the New York Academy of Sciences AU - Heinzen, Robert A AD - Department of Molecular Biology, University of Wyoming, Laramie, Wyoming, 82071-3944, USA, rheinzen@niaid.nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 535 EP - 547 PB - Blackwell Publishing Ltd., 9600 Garsington Road VL - 990 IS - 1 SN - 0077-8923, 0077-8923 KW - Microbiology Abstracts B: Bacteriology KW - motility KW - actin KW - N-WASP KW - Arp2-3 complex KW - rickettsia KW - Wiskott-Aldrich syndrome KW - Motility KW - Typhus KW - Data processing KW - Spotted fevers KW - Plasma membranes KW - Tails KW - Microscopy KW - Actin KW - Pathogens KW - Immunofluorescence KW - J 02320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19309842?accountid=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=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Rickettsial+Actin-Based+Motility&rft.au=Heinzen%2C+Robert+A&rft.aulast=Heinzen&rft.aufirst=Robert&rft.date=2003-06-01&rft.volume=990&rft.issue=1&rft.spage=535&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fj.1749-6632.2003.tb07424.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Wiskott-Aldrich syndrome; Typhus; Motility; Spotted fevers; Data processing; Plasma membranes; Tails; Microscopy; Actin; Immunofluorescence; Pathogens DO - http://dx.doi.org/10.1111/j.1749-6632.2003.tb07424.x ER - TY - JOUR T1 - Fusogenicity of the Coxiella burnetii Parasitophorous Vacuole AN - 19308398; 8396748 AB - AbstractThis study investigated whether C. burnetii protein synthesis and replication is required for maintenance of the fusogenic character of the Coxiella parasitophorous vacuole (PV). Vero cells were infected with C. burnetii, (Nine Mile strain in phase II) at a multiplicity of infection of approximately 10 and simultaneously treated with bacteriostatic concentrations of chloramphenicol or carbenicillin. At 96 h post-infection, cells were viewed by phase contrast microscopy for PV maturation. Mature, spacious PV containing multiple nonreplicating C. burnetii were clearly visible in infected Vero cells treated with the cell wall inhibitor carbenicillin. Conversely, mature, spacious PV did not form in cells treated with the protein synthesis inhibitor chloramphenicol. Rather, immunofluorescence microscopy revealed individual C. burnetii in small, tight PV scattered throughout the cytoplasm. Like mature PV, these PV localized with the lysosomal glycoprotein LAMP-1, but not the early endosome protein EEA.1. This result suggests that de novo C. burnetii protein synthesis, but not replication, is required for homotypic fusion and maturation of nascent C. burnetii PV. We next examined whether sustained C. burnetii protein synthesis is necessary for maintenance of PV fusogenicity. J774A.1 murine macrophage-like cells with mature C. burnetii PV were incubated with latex beads and the trafficking of beads to PV was quantified. Fusion of PV with bead-laden vacuoles was severely inhibited in cells treated with chloramphenicol. These results suggest that sustained C. burnetii protein synthesis is required for PV fusion with other vacuoles of the endocytic pathway. JF - Annals of the New York Academy of Sciences AU - Howe, Dale AU - MELNICAKOVA, JANA AU - Barak, Imrich AU - Heinzen, Robert A AD - University of Wyoming, Department of Molecular Biology, Laramie, Wyoming 82071-3944, USA, rheinzen@niaid.nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 556 EP - 562 PB - Blackwell Publishing Ltd., 9600 Garsington Road VL - 990 IS - 1 SN - 0077-8923, 0077-8923 KW - Microbiology Abstracts B: Bacteriology KW - Coxiella KW - parasitophorous vacuole KW - protein synthesis KW - fusion KW - Chloramphenicol KW - Protein biosynthesis KW - Vero cells KW - Replication KW - Latex beads KW - Immunofluorescence KW - LAMP-1 protein KW - Carbenicillin KW - Coxiella burnetii KW - endosomes KW - Cytoplasm KW - Vacuoles KW - Microscopy KW - Glycoproteins KW - Multiplicity of infection KW - Cell walls KW - J 02320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19308398?accountid=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=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Fusogenicity+of+the+Coxiella+burnetii+Parasitophorous+Vacuole&rft.au=Howe%2C+Dale%3BMELNICAKOVA%2C+JANA%3BBarak%2C+Imrich%3BHeinzen%2C+Robert+A&rft.aulast=Howe&rft.aufirst=Dale&rft.date=2003-06-01&rft.volume=990&rft.issue=1&rft.spage=556&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fj.1749-6632.2003.tb07426.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Chloramphenicol; Protein biosynthesis; Vero cells; Replication; Latex beads; Immunofluorescence; Carbenicillin; LAMP-1 protein; parasitophorous vacuole; endosomes; Cytoplasm; Microscopy; Vacuoles; Glycoproteins; Multiplicity of infection; Cell walls; Coxiella burnetii DO - http://dx.doi.org/10.1111/j.1749-6632.2003.tb07426.x ER - TY - JOUR T1 - Induction of permeability changes and death of vertebrate cells is modulated by the virulence of Entamoeba spp. isolates AN - 18946346; 5731578 AB - Although Entamoeba histolytica is capable of inducing an apoptotic response in vertebrate cells in vitro (Cell. Microbiol. 2 (2000) 617), it is not known whether vertebrate cell death requires direct amoeba-vertebrate cell contact or simply the presence of amoebae in the area of the vertebrate cells. In addition, Entamoeba spp. vary in their virulence and pathogenicity. The potential effects of these critical parameters also have not been elucidated. We tested the virulent HM-1:IMSS isolate and the non-virulent Rahman isolate of E. histolytica, and the non-virulent E. dispar CYNO16:TPC isolate against two vertebrate cell lines, HeLa and Chinese hamster ovary cells in vitro using ethidium homodimer as a fluorescent indicator of changes in vertebrate cell permeability. Fluorescence appeared in vertebrate cell nuclei within approximately 2-3 min of contact between HM-1 amoebae and vertebrate cells independent of vertebrate cell type. However, vertebrate cells in the immediate vicinity of but not contacted by HM-1 amoebae were not affected. In contrast, although both E. histolytica Rahman and E. dispar CYNO16 amoebae moved freely among and contacted vertebrate cells, the nuclei of the vertebrate cells never fluoresced implying that the cells remained alive and impermeant to the ethidium homodimer. This is the first demonstration that direct contact between virulent amoebae and vertebrate cells is required to kill vertebrate cells and that the process is restricted to virulent Entamoeba isolates. An understanding at the molecular level of the processes involved could help to reduce the pathology associated with this parasite. JF - Parasitology International AU - Dvorak, JA AU - Kobayashi, S AU - Nozaki, T AU - Takeuchi, T AU - Matsubara, C AD - Laboratory of Malaria and Vector Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA, jdvorak@niaid.nih.gov Y1 - 2003/06// PY - 2003 DA - June 2003 SP - 169 EP - 173 VL - 52 IS - 2 SN - 1383-5769, 1383-5769 KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Virulence KW - Parasites KW - Cell death KW - Human diseases KW - Apoptosis KW - Pathology KW - Protozoan diseases KW - Entamoeba histolytica KW - Entamoeba dispar KW - Membrane permeability KW - K 03091:Protozoa: animal KW - Q1 08484:Species interactions: parasites and diseases KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18946346?accountid=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=Parasitology+International&rft.atitle=Induction+of+permeability+changes+and+death+of+vertebrate+cells+is+modulated+by+the+virulence+of+Entamoeba+spp.+isolates&rft.au=Dvorak%2C+JA%3BKobayashi%2C+S%3BNozaki%2C+T%3BTakeuchi%2C+T%3BMatsubara%2C+C&rft.aulast=Dvorak&rft.aufirst=JA&rft.date=2003-06-01&rft.volume=52&rft.issue=2&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Parasitology+International&rft.issn=13835769&rft_id=info:doi/10.1016%2FS1383-5769%2802%2900090-9 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2016-12-21 N1 - SubjectsTermNotLitGenreText - Virulence; Parasites; Human diseases; Protozoan diseases; Pathology; Cell death; Apoptosis; Membrane permeability; Entamoeba histolytica; Entamoeba dispar DO - http://dx.doi.org/10.1016/S1383-5769(02)00090-9 ER - TY - JOUR T1 - Iron intake and regulation: implications for iron deficiency and iron overload AN - 18886195; 5744847 AB - Although iron deficiency anemia is the most common nutritional deficiency worldwide and in the United States, the health effects of iron overload merit increased attention. In the United States, public health interventions such as fortification and enrichment of foods with iron were undertaken to reduce the prevalence of iron deficiency anemia and improve health. These measures, along with iron supplementation, remain controversial, because additional exposure to dietary iron places some segments of the population at increased risk of iron excess. The health consequences of unmistakable iron excess are exemplified by hemochromatosis, an iron storage disease associated with liver damage further exacerbated by alcohol consumption. Progressive liver damage associated with this condition is generally attributed to increased oxidative stress. In otherwise healthy individuals, more modest levels of iron storage may occur if iron is provided by supplements or otherwise added to the food supply. Increased iron intake and storage have been linked to a variety of chronic diseases. The associations are not firmly established but are of considerable public health importance. JF - Alcohol AU - Swanson, CA AD - Office of Dietary Supplements, National Institutes of Health, 6100 Executive Boulevard, Room 3B01, MSC 7517, Bethesda, MD 20892-7517, USA, Swansonc@OD.NIH.GOV Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 99 EP - 102 VL - 30 IS - 2 SN - 0741-8329, 0741-8329 KW - deficiency KW - intake KW - man KW - overload KW - regulation KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18886195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol&rft.atitle=Iron+intake+and+regulation%3A+implications+for+iron+deficiency+and+iron+overload&rft.au=Swanson%2C+CA&rft.aulast=Swanson&rft.aufirst=CA&rft.date=2003-06-01&rft.volume=30&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Alcohol&rft.issn=07418329&rft_id=info:doi/10.1016%2FS0741-8329%2803%2900103-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0741-8329(03)00103-4 ER - TY - JOUR T1 - Hepatic iron overload in alcoholic liver disease: why does it occur and what is its role in pathogenesis? AN - 18885211; 5744848 AB - Iron overload is frequently observed in alcoholic liver disease. However, it is not known why hepatic iron accumulation occurs or how it contributes to disease progression. In this review, information about the role of iron in the pathophysiology of liver disease is reviewed and discussed. JF - Alcohol AU - Rouault, T A AD - Section on Human Iron Metabolism, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Building 18, Room 101, National Institutes of Health, Bethesda, MD 20892, USA, trou@helix.nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 103 EP - 106 VL - 30 IS - 2 SN - 0741-8329, 0741-8329 KW - man KW - overload KW - Toxicology Abstracts KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18885211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol&rft.atitle=Hepatic+iron+overload+in+alcoholic+liver+disease%3A+why+does+it+occur+and+what+is+its+role+in+pathogenesis%3F&rft.au=Rouault%2C+T+A&rft.aulast=Rouault&rft.aufirst=T&rft.date=2003-06-01&rft.volume=30&rft.issue=2&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Alcohol&rft.issn=07418329&rft_id=info:doi/10.1016%2FS0741-8329%2803%2900102-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0741-8329(03)00102-2 ER - TY - JOUR T1 - A summary of evidence on radiation exposures received near to the Semipalatinsk nuclear weapons test site in Kazakhstan AN - 18885174; 5742409 AB - The presently available evidence about the magnitude of doses received by members of the public living in villages in the vicinity of Semipalatinsk nuclear test in Kazakhstan, particularly with respect to external radiation, while preliminary, is conflicting. The village of Dolon, in particular, has been identified for many years as the most highly exposed location in the vicinity of the test site. Previous publications cited external doses of more than 2 Gy to residents of Dolon while an expert group assembled by the WHO in 1997 estimated that external doses were likely to have been less than 0.5 Gy. In 2001, a larger expert group workshop was held in Helsinki jointly by the WHO, the National Cancer Institute of the United States, and the Radiation and Nuclear Safety Authority of Finland, with the expressed purpose to acquire data to evaluate the state of knowledge concerning doses received in Kazakhstan. This paper summarizes evidence presented at that workshop. External dose estimates from calculations based on sparse physical measurements and biodosimetric estimates based on chromosome abnormalities and electron paramagnetic resonance from a relatively small sample of teeth do not agree well. The physical dose estimates are generally higher than the biodosimetric estimates (1 Gy or more compared to 0.5 Gy or less). When viewed in its entirety, the present body of evidence does not appear to support external doses greater than 0.5 Gy; however, research is continuing to try and resolve the difference in dose estimates from the different methods. Thyroid doses from internal irradiation, which can only be estimated via calculation, are expected to have been several times greater than the doses from external irradiation, especially where received by small children. JF - Health Physics AU - Simon, S L AU - Baverstock, K F AU - Lindholm, C AD - National Cancer Institute, 6120 Executive Blvd., MSC 7238, Executive Plaza South, Room 7089, Bethesda, MD 20892, USA, ssimon@mail.nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 718 EP - 725 VL - 84 IS - 6 SN - 0017-9078, 0017-9078 KW - exposure KW - nuclear weapon test sites KW - Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - X 24210:Radiation & radioactive materials KW - H 8000:Radiation Safety/Electrical Safety KW - P 8000:RADIATION UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18885174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+Physics&rft.atitle=A+summary+of+evidence+on+radiation+exposures+received+near+to+the+Semipalatinsk+nuclear+weapons+test+site+in+Kazakhstan&rft.au=Simon%2C+S+L%3BBaverstock%2C+K+F%3BLindholm%2C+C&rft.aulast=Simon&rft.aufirst=S&rft.date=2003-06-01&rft.volume=84&rft.issue=6&rft.spage=718&rft.isbn=&rft.btitle=&rft.title=Health+Physics&rft.issn=00179078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Biological markers of cocaine addiction: implications for medications development AN - 18876962; 5735096 AB - The search for effective medications for cocaine addiction has been elusive. The failure to find such medications so far could be due to poor understanding of the underlying biology both in the premorbid condition and following the disease state of chronic cocaine use. Population heterogeneity could be a major factor in response to medications. In an attempt to highlight the issue of biomarkers we reviewed physiological, neuroendocrine and neuroimaging studies to identify specific biological changes/markers that could be used to characterize subgroups among chronic cocaine users. Merging the biology within medications studies of cocaine abusers could prove useful for targeting specific pharmacological agents to subgroups of patients, prediction of response to medication and relapse to use. JF - Addiction Biology AU - Elkashef, A AU - Vocci, F AD - Division of Treatment, Research and Development (DTR&D), National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), 6001 Executive Boulevard, Room 4123, MSC 9551, Bethesda, MD 20892-9551, USA, ae8a@nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 123 EP - 139 VL - 8 IS - 2 SN - 1355-6215, 1355-6215 KW - biomarkers KW - man KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - X 24180:Social poisons & drug abuse KW - N3 11139:Toxicological and psychoactive drug correlates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18876962?accountid=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=Addiction+Biology&rft.atitle=Biological+markers+of+cocaine+addiction%3A+implications+for+medications+development&rft.au=Elkashef%2C+A%3BVocci%2C+F&rft.aulast=Elkashef&rft.aufirst=A&rft.date=2003-06-01&rft.volume=8&rft.issue=2&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Addiction+Biology&rft.issn=13556215&rft_id=info:doi/10.1080%2F1355621031000117356 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1080/1355621031000117356 ER - TY - JOUR T1 - Construction and characterization of rhesus monkey rotavirus (MMU18006)- or bovine rotavirus (UK)-based serotype G5, G8, G9 or G10 single VP7 gene substitution reassortant candidate vaccines AN - 18848660; 5639004 AB - Group A rotaviruses are the single most important etiologic agents of severe diarrhea of infants and young children worldwide and have been estimated to be responsible for approximately 650,000-800,000 deaths annually in children <5- year-old in the developing countries. Thus, the development of a safe and effective rotavirus vaccine has been a global public health goal. Epidemiologic surveillance of rotavirus VP7 (G) serotypes-genotypes conducted in various populations throughout the world has repeatedly shown that approximately 90% of the typeable rotavirus isolates belong to G1-G4. For these reasons, we have developed a rhesus rotavirus (RRV)-based or bovine rotavirus (UK)-based quadrivalent vaccine which is designed to provide antigenic coverage for G1-G4. More recently, G serotypes-genotypes other than G1-G4, including G5, G8-G10, have been detected in various parts of the world. Although the occurrence of such uncommon G types, except for G9, has been focal, still, in order to 'be ready and prepared', we have constructed and characterized eight additional reassortant rotavirus vaccines, each of which bears a single human or bovine VP7 gene encoding G serotype 5, 8, 9 or 10 specificity and the remaining 10 genes of RRV strain MMU18006 or bovine rotavirus strain UK. These candidate vaccines could be evaluated singly in special populations or in combination with a RRV- or an UK-based quadrivalent vaccine to broaden its G serotype specificity. JF - Vaccine AU - Hoshino, Y AU - Jones, R W AU - Ross, J AU - Kapikian, A Z AD - Epidemiology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 50, Room 6308, 50 South Drive, MSC 8026, Bethesda, MD 20892-8026, USA, thoshino@niaid.nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 3003 EP - 3010 VL - 21 IS - 21-22 SN - 0264-410X, 0264-410X KW - Rhesus monkey KW - VP7 gene KW - cattle KW - epidemiology KW - man KW - monkeys KW - surveillance KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Agricultural and Environmental Biotechnology Abstracts; Immunology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W2 32365:Vaccines KW - A 01097:Viruses KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18848660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Construction+and+characterization+of+rhesus+monkey+rotavirus+%28MMU18006%29-+or+bovine+rotavirus+%28UK%29-based+serotype+G5%2C+G8%2C+G9+or+G10+single+VP7+gene+substitution+reassortant+candidate+vaccines&rft.au=Hoshino%2C+Y%3BJones%2C+R+W%3BRoss%2C+J%3BKapikian%2C+A+Z&rft.aulast=Hoshino&rft.aufirst=Y&rft.date=2003-06-01&rft.volume=21&rft.issue=21-22&rft.spage=3003&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2FS0264-410X%2803%2900120-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0264-410X(03)00120-8 ER - TY - JOUR T1 - Introduction: What Are the Issues in Addressing the Allergenic Potential of Genetically Modified Foods? AN - 18828628; 5714970 AB - There is growing concern among the general public and the scientific community regarding the potential toxicity of genetically modified organisms (GMOs). The use of biotechnology to enhance pest resistance or nutritional value has raised a number of fundamental questions including the consequences of insertion of reporter genes, the spread of resistance genes to surrounding plants, and the use of suicide genes to prohibit reuse of seed from engineered plants. Of particular interest is the ability of proteins from GMOs to elicit potentially harmful immunologic responses, including allergic hypersensitivity. The lack of information of the potential toxicity of these products suggests a need to identify the critical issues and research needs regarding these materials and to develop testing strategies to examine the allergenicity of these compounds. JF - Environmental Health Perspectives AU - Metcalfe, D D AD - Laboratory of Allergic Diseases, NIAID, NIH, Bldg. 10, Rm. 11C205, MSC 1881, 10 Center Dr., Bethesda, MD 20892-1881, USA, dean_metcalfe@nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 1110 EP - 1113 PB - NIH, Government Printing Office VL - 111 IS - 8 SN - 0091-6765, 0091-6765 KW - genetically modified foods KW - man KW - suicide genes KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Toxicology Abstracts; Bioengineering Abstracts KW - X 24120:Food, additives & contaminants KW - W4 330:Biopolymers & Food Biotechnology KW - W 30965:Miscellaneous, Reviews KW - F 06844:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18828628?accountid=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=Environmental+Health+Perspectives&rft.atitle=Introduction%3A+What+Are+the+Issues+in+Addressing+the+Allergenic+Potential+of+Genetically+Modified+Foods%3F&rft.au=Metcalfe%2C+D+D&rft.aulast=Metcalfe&rft.aufirst=D&rft.date=2003-06-01&rft.volume=111&rft.issue=8&rft.spage=1110&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Fehp.5810 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1289/ehp.5810 ER - TY - JOUR T1 - Nocardia veterana as a Pathogen in North American Patients AN - 18814134; 5684601 AB - The molecular methodologies used in our laboratories have allowed us to define a group of Nocardia isolates from clinical samples which resemble the type strain of Nocardia veterana. Three patient isolates and the type strain of N. veterana gave identical and distinctive restriction fragment length polymorphisms (RFLPs) for an amplified portion of the 16S rRNA gene. These three isolates and the N. veterana type strain also gave identical RFLPs for an amplified portion of the 65-kDa heat shock protein gene, but this pattern was identical to that obtained for the Nocardia nova type strain. Sequence analysis of both a 1,359-bp region of the 16S rRNA gene and a 441-bp region of the heat shock protein gene of the patient isolates showed 100% identities with the same regions of the N. veterana type strain. DNA-DNA hybridization of the DNA of one of the patient isolates with the DNA of the N. veterana type strain showed a relative binding ratio of 82%, with 0% divergence, confirming that the isolate was N. veterana. Biochemical and susceptibility testing showed no significant differences among the patient isolates and the N. veterana type strain. Significantly, the results of antimicrobial susceptibility testing obtained for our isolates were similar to those obtained for N. nova, indicating that susceptibility testing alone cannot discriminate between these species. We present two case studies which show that N. veterana is a causative agent of pulmonary disease in immunocompromised patients residing in North America. We also describe difficulties encountered in using 16S rRNA gene sequences alone for discrimination of N. veterana from the related species Nocardia africana and N. nova because of the very high degree of 16S rRNA gene similarity among them. JF - Journal of Clinical Microbiology AU - Conville, P S AU - Brown, J M AU - Steigerwalt, A G AU - Lee, J-W AU - Byrer, DE AU - Anderson, V L AU - Dorman, E AU - Holland, T M AU - Cahill, B AU - Carroll, K C AU - Witebsky, F G AD - Microbiology Service, Department of Laboratory Medicine, 10 Center Dr., MSC 1508, National Institutes of Health, Bethesda, MD 20892-1508, pconville@nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 2560 EP - 2568 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 41 IS - 6 SN - 0095-1137, 0095-1137 KW - man KW - Microbiology Abstracts B: Bacteriology KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18814134?accountid=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=Nocardia+veterana+as+a+Pathogen+in+North+American+Patients&rft.au=Conville%2C+P+S%3BBrown%2C+J+M%3BSteigerwalt%2C+A+G%3BLee%2C+J-W%3BByrer%2C+DE%3BAnderson%2C+V+L%3BDorman%2C+E%3BHolland%2C+T+M%3BCahill%2C+B%3BCarroll%2C+K+C%3BWitebsky%2C+F+G&rft.aulast=Conville&rft.aufirst=P&rft.date=2003-06-01&rft.volume=41&rft.issue=6&rft.spage=2560&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/10.1128%2FJCM.41.6.2560-2568.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JCM.41.6.2560-2568.2003 ER - TY - JOUR T1 - How many high production chemicals are rodent carcinogens? Why should we care? What do we need to do about it? AN - 18805214; 5658009 AB - High production volume (HPV) chemicals are produced in or imported to the US in amounts greater than 1 million pounds per chemical per year. The EPA has identified thousands of HPVs. Due to their abundance, such chemicals bring a substantial risk for human exposure, and as a result some level of adverse consequences to health are to be expected. In order to examine the potential for cancer risk associated with HPVs, this paper examines HPVs that have been tested in the National Toxicology Program's rodent cancer bioassay. The chemicals tested in the bioassay represent a small sample of the universe of environmental chemicals to which people are exposed. Unexpectedly, 60% of the 128 HPVs evaluated in the bioassay proved to be rodent carcinogens. This value compares to a predicted prevalence of only 16.5% carcinogens in a previous study. The previous study concluded that HPVs were less likely to be toxic by a variety of other test criteria as well. However, the approach involved identifying putative carcinogens using quantitative chemical structure-activity relationships (QSAR) in contrast to the direct tabulation of bioassay test results performed here. Detailed examination of bioassay results reveals that test outcomes depend heavily on route of administration as well as on dose level, sex, strain, and species used. Since most of these factors have little or no apparent relationship to chemical structure, results of this study suggest that QSAR, as well as virtually all other alternative methods, may not generally provide accurate predictions of carcinogenic potential. As we wait for efficient and effective methods for predicting carcinogens to be developed, people continue to be exposed to environmental carcinogens. Progress on regulating environmental carcinogens as well as on developing more effective test methods has been minimal since 'war on cancer' began approximately 30 years ago. The present study questions whether the current strategy for dealing with environmental carcinogens will ever be successful. Close examination of rodent cancer test results seems to suggest that almost all chemicals may have carcinogenic potential in some genotypes under some exposure circumstances. If this hypothesis is correct, it would explain the general lack of progress in developing methods to differentiate carcinogens from noncarcinogens. A completely new strategy for dealing with cancer caused by exposures to environmental chemicals seems to be needed. JF - Mutation Research-Reviews in Mutation Research AU - Johnson, F M AD - National Institute of Environmental Health Sciences, Mail Drop EC-31, Research Triangle Park, NC 27709, USA Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 201 EP - 215 VL - 543 IS - 3 SN - 1383-5742, 1383-5742 KW - High production volume chemicals KW - Rodents KW - Genetics Abstracts; Toxicology Abstracts KW - X 24250:Reviews KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18805214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Reviews+in+Mutation+Research&rft.atitle=How+many+high+production+chemicals+are+rodent+carcinogens%3F+Why+should+we+care%3F+What+do+we+need+to+do+about+it%3F&rft.au=Johnson%2C+F+M&rft.aulast=Johnson&rft.aufirst=F&rft.date=2003-06-01&rft.volume=543&rft.issue=3&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Reviews+in+Mutation+Research&rft.issn=13835742&rft_id=info:doi/10.1016%2FS1383-5742%2802%2900091-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S1383-5742(02)00091-1 ER - TY - JOUR T1 - Cell-Matrix Adhesions on Poly(vinyl alcohol) Hydrogels AN - 18793867; 5661894 AB - Cell-matrix adhesions regulate cell morphology, intracellular signaling, gene expression, and phenotype. Understanding how different methods of attaching matrix proteins to substrates affect the molecular arrangement of these adhesions offers the possibility of controlling cell function and architecture. The goal of this study was to visualize and quantify the cell-matrix adhesions formed by human fibroblasts on the matrix protein fibronectin covalently attached to poly(vinyl) alcohol (PVA) hydrogels. These adhesions were then compared with the cell adhesions formed in routine cell culture on fibronectin noncovalently coated onto glass coverslips or those formed on fibronectin covalently immobilized onto glass coverslips. Cell adhesions were characterized by immunofluorescence confocal microscopy utilizing paxillin as a marker for focal adhesions and alpha sub(5) integrin as a marker for fibrillar adhesions. As expected, distinct focal and fibrillar adhesions were observed in routine cell culture on coverslips coated noncovalently with fibronectin. Cells cultured on fibronectin covalently linked to PVA demonstrated diminished spatial separation of paxillin and alpha sub(5) integrin, accompanied by a reduction in fibrillar adhesions and fibronectin fibrillogenesis. Cells on fibronectin covalently immobilized on glass displayed the strongest marker colocalization and the most complete loss of fibrillar adhesions and lack of fibrillogenesis. These results indicate that fibronectin-conjugated PVA promotes the formation of cell adhesion structures intermediate in composition between those formed on noncovalently attached and covalently immobilized fibronectin. Furthermore, they imply that bioactive polymers can selectively induce specific cell-matrix adhesions, a characteristic that may have consequences in various tissue-engineering applications. JF - Tissue Engineering AU - Zajaczkowski, M B AU - Cukierman, E AU - Galbraith, C G AU - Yamada, K M AD - CDBRB, NIDCR, NIH, Building 30, Room 421, 30 Convent Drive, MSC 4370, Bethesda, MD 20892-4370, USA, Kenneth.Yamada@nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 525 EP - 533 VL - 9 IS - 3 SN - 1076-3279, 1076-3279 KW - fibronectin KW - hydrogels KW - man KW - paxillin KW - polyvinyl alcohol KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18793867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tissue+Engineering&rft.atitle=Cell-Matrix+Adhesions+on+Poly%28vinyl+alcohol%29+Hydrogels&rft.au=Zajaczkowski%2C+M+B%3BCukierman%2C+E%3BGalbraith%2C+C+G%3BYamada%2C+K+M&rft.aulast=Zajaczkowski&rft.aufirst=M&rft.date=2003-06-01&rft.volume=9&rft.issue=3&rft.spage=525&rft.isbn=&rft.btitle=&rft.title=Tissue+Engineering&rft.issn=10763279&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Development of a quantitative antigen-specific cell-based ELISA for the 7G7/B6 monoclonal antibody directed toward IL-2R alpha AN - 18791503; 5656807 AB - Interleukin-2 receptor alpha (IL-2R alpha , CD25) has been identified as a valuable target for immunotherapy. The 7G7/B6 monoclonal antibody, a mouse IgG2a kappa, recognizes an epitope of the IL-2R alpha peptide, other than that identified by anti-Tac. This antibody is currently being explored for potential therapeutic and diagnostic applications. Here, we show a cell-based enzyme-linked immunosorbent assay (CbELISA) method for quantitative measurement of the binding activity of the 7G7/B6 antibody to the Kit-225-iG3 cell line expressing IL-2R alpha antigen on the cell surface. The cell- and antigen-specificity of the assay was established using specific cell lines and irrelevant control antibodies. Satisfactory binding curves were demonstrated with Kit-225-iG3 cells grown between 3 and 25 passages in culture and at seed densities of 210 super(5)-410 super(6) cells/well. The assay shows reproducible dose-response curves in the concentration range of 10-1000 ng/ml. The assay validation data presented here indicate that this CbELISA assay is quantitative, reproducible, robust, precise, and can be used to test the biological activity, lot to lot comparison, and stability of 7G7/B6 monoclonal antibody. JF - Journal of Immunological Methods AU - Yang, X Y AU - Jiang, H AU - Hartmann, W K AU - Mitra, G AU - Soman, G AD - Bioanalytical Development Laboratory, Biopharmaceutical Development Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Building 458, Room 17, P.O. Box B, Frederick, MD 21702, USA, somang@mail.ncifcrf.gov Y1 - 2003/06/01/ PY - 2003 DA - 2003 Jun 01 SP - 87 EP - 100 PB - Elsevier Science B.V. VL - 277 IS - 1-2 SN - 0022-1759, 0022-1759 KW - interleukin 2 receptors KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33240:Immunology KW - F 06720:ELISA KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18791503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Development+of+a+quantitative+antigen-specific+cell-based+ELISA+for+the+7G7%2FB6+monoclonal+antibody+directed+toward+IL-2R+alpha&rft.au=Yang%2C+X+Y%3BJiang%2C+H%3BHartmann%2C+W+K%3BMitra%2C+G%3BSoman%2C+G&rft.aulast=Yang&rft.aufirst=X&rft.date=2003-06-01&rft.volume=277&rft.issue=1-2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/10.1016%2FS0022-1759%2803%2900178-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0022-1759(03)00178-9 ER - TY - JOUR T1 - Plasmid Stability during In Vitro Propagation of Borrelia burgdorferi Assessed at a Clonal Level AN - 18776824; 5634525 AB - Borrelia burgdorferi causes Lyme disease in humans. The genome of the sequenced type strain B31 MI consists of a linear chromosome, 12 linear plasmids, and 9 circular plasmids. Previous studies by other investigators indicated that some of these plasmids are essential for the survival of the spirochetes in vivo but not in vitro. We have studied plasmid stability during in vitro growth at 23 and 35 degree C, conditions that approximate the temperatures of the tick vector and the mammalian host, respectively. Starting with two clones that have all 21 plasmids, we investigated plasmid maintenance within the population and on a clonal level. After three passages (27 generations), the cultures were no longer homogeneous and some derivative clones had already lost multiple plasmids. Despite this, one of six clones analyzed after 25 passages (225 generations) retained all but one plasmid (cp9) and was able to complete the mouse-tick-mouse infectious cycle. We analyzed protein composition and regulation of gene expression of clones differing in plasmid content after serial passages. All clones tested exhibited temperature-regulated expression of several proteins, including OspC. In addition, analysis of cultures inoculated from frozen stocks suggests that freezing and/or thawing contributes to heterogeneity in the outgrowth population with respect to plasmid content. Our investigations show that in vitro propagation of a clone leads to a heterogeneous population but that virulent clones can persist through extended passage. We therefore conclude that isogenicity of clones must be confirmed irrespective of their in vitro passage history. JF - Infection and Immunity AU - Grimm, D AU - Elias, A F AU - Tilly, K AU - Rosa, P A AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840, dgrimm@niaid.nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 3138 EP - 3145 VL - 71 IS - 6 SN - 0019-9567, 0019-9567 KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18776824?accountid=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=Plasmid+Stability+during+In+Vitro+Propagation+of+Borrelia+burgdorferi+Assessed+at+a+Clonal+Level&rft.au=Grimm%2C+D%3BElias%2C+A+F%3BTilly%2C+K%3BRosa%2C+P+A&rft.aulast=Grimm&rft.aufirst=D&rft.date=2003-06-01&rft.volume=71&rft.issue=6&rft.spage=3138&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.71.6.3138-3145.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.71.6.3138-3145.2003 ER - TY - JOUR T1 - Evaluation of the compatibility of a second generation recombinant anthrax vaccine with aluminum-containing adjuvants AN - 18775564; 5639005 AB - Recombinant protective antigen (rPA) is the active pharmaceutical ingredient in a second generation anthrax vaccine undergoing pre-clinical evaluation. This rPA vaccine differs from the currently licensed vaccine, anthrax vaccine adsorbed (AVA), in that the sole component is a recombinant form of protective antigen (PA). Unlike AVA the rPA vaccine contains no lethal factor (LF) or edema factor (EF), components of the two bipartite toxins, nor many other Bacillus anthracis-related contaminating proteins that are present in AVA. The proposed clinical protocol involves adsorption of the rPA to an aluminum-based adjuvant. The adsorptive characteristics of rPA and two aluminum-containing adjuvants were examined in a physiological buffer with and without EDTA. Based on the pI of rPA (pI=5.6) and the zero charge point of aluminum hydroxide adjuvant (11.5) and aluminum phosphate adjuvant (4.5), it was predicted and demonstrated that rPA bound in a more efficient manner to aluminum hydroxide adjuvant than to aluminum phosphate adjuvant in the physiological buffer. Binding of the rPA to the aluminum hydroxide adjuvant was decreased by increasing amounts of phosphate in the buffer. The adsorptive capacity for rPA onto aluminum hydroxide adjuvant in the physiological buffer and in water were calculated to be 0.46 mg rPA/mg aluminum in DPBS and 0.73 mg rPA/mg aluminum in water. This study also demonstrated that upon desorption from the aluminum hydroxide adjuvant the rPA was physically intact and free of detectable aggregates. Further, the eluted material was biologically active in an in vitro cytotoxicity assay. Desorption was only possible after an overnight incubation of 2-8 degree C and not after a room temperature incubation reflecting increased contact with the aluminum hydroxide adjuvant over time. These data suggest that the interaction between rPA and aluminum hydroxide adjuvant is predominantly electrostatic in character. JF - Vaccine AU - Jendrek, S AU - Little, S F AU - Hem, S AU - Mitra, G AU - Giardina, S AD - Building 320, SAIC-Frederick Inc. National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702, USA, sjendrek@ncifcrf.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 3011 EP - 3018 VL - 21 IS - 21-22 SN - 0264-410X, 0264-410X KW - Edema factor KW - Lethal factor KW - edema factor KW - lethal factor KW - protective antigen KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18775564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Evaluation+of+the+compatibility+of+a+second+generation+recombinant+anthrax+vaccine+with+aluminum-containing+adjuvants&rft.au=Jendrek%2C+S%3BLittle%2C+S+F%3BHem%2C+S%3BMitra%2C+G%3BGiardina%2C+S&rft.aulast=Jendrek&rft.aufirst=S&rft.date=2003-06-01&rft.volume=21&rft.issue=21-22&rft.spage=3011&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2FS0264-410X%2803%2900109-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0264-410X(03)00109-9 ER - TY - JOUR T1 - Coaggregation-Mediated Interactions of Streptococci and Actinomyces Detected in Initial Human Dental Plaque AN - 18774713; 5634472 AB - Streptococci and actinomyces that initiate colonization of the tooth surface frequently coaggregate with each other as well as with other oral bacteria. These observations have led to the hypothesis that interbacterial adhesion influences spatiotemporal development of plaque. To assess the role of such interactions in oral biofilm formation in vivo, antibodies directed against bacterial surface components that mediate coaggregation interactions were used as direct immunofluorescent probes in conjunction with laser confocal microscopy to determine the distribution and spatial arrangement of bacteria within intact human plaque formed on retrievable enamel chips. In intrageneric coaggregation, streptococci such as Streptococcus gordonii DL1 recognize receptor polysaccharides (RPS) borne on other streptococci such as Streptococcus oralis 34. To define potentially interactive subsets of streptococci in the developing plaque, an antibody against RPS (anti-RPS) was used together with an antibody against S. gordonii DL1 (anti-DL1). These antibodies reacted primarily with single cells in 4-h-old plaque and with mixed-species microcolonies in 8-h-old plaque. Anti-RPS-reactive bacteria frequently formed microcolonies with anti-DL1-reactive bacteria and with other bacteria distinguished by general nucleic acid stains. In intergeneric coaggregation between streptococci and actinomyces, type 2 fimbriae of actinomyces recognize RPS on the streptococci. Cells reactive with antibody against type 2 fimbriae of Actinomyces naeslundii T14V (anti-type-2) were much less frequent than either subset of streptococci. However, bacteria reactive with anti-type-2 were seen in intimate association with anti-RPS-reactive cells. These results are the first direct demonstration of coaggregation-mediated interactions during initial plaque accumulation in vivo. Further, these results demonstrate the spatiotemporal development and prevalence of mixed-species communities in early dental plaque. The transcription of mecA, the gene required for oxacillin resistance in staphylococci, was quantified in a collection of 65 geographically and genetically diverse clinical and 8 defined laboratory Staphylococcus aureus isolates. mecA transcription was measured by real-time reverse transcription-PCR, confirmed by Northern blot analysis, and correlated with the presence and DNA sequence of the two mecA repressors, mecI and blaI. Isolates were first examined that contained mecI and/or blaI with wild- type sequence. BlaI provided significantly more repression of mecA transcription than did MecI, unrelated to blaI genetic location. Both together repressed mecA better than either one alone. In clinical isolates containing only wild-type mecI, mecA transcription repression was 10- to 25-fold less effective than that seen in previously studied constructs derived from strain N315. There was a difference in the mecI ribosomal binding site (RBS) between the clinical isolates (GGAA) and N315 (GGAG). The GGAA RBS was associated with 5.5- to 7.3-fold less mecA repression than GGAG in isogenic constructs. The values generated for wild-type repressors were compared to those in 26 isolates containing mecI mutations. mecA transcription appeared to be repressed only by BlaI in isolates with mecI nonsense and frameshift mutations. In contrast, mecI repression seemed to be partially or fully retained in many of the isolates with mecI and one isolate with blaI missense mutations, providing structure-function correlates with the site and type of mutation. We conclude that mecA repressor activity is highly variable in clinical S. aureus isolates due to mecI mutations, RBS polymorphisms, and unidentified genomic adaptations. JF - Journal of Bacteriology AU - Palmer, RJ Jr AU - Gordon, S M AU - Cisar, JO AU - Kolenbrander, P E AU - Rosato, A E AU - Craig, WA AU - Archer, G L AD - National Institutes of Health/NIDCR, Building 30, Room 310, 30 Convent Dr., MSC 4350, Bethesda, MD 20892-4350, pkolenbrander@dir.nidcr.nih.gov pkolenbrander@dir.nidcr.nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 3400 EP - 3409 VL - 185 IS - 11 SN - 0021-9193, 0021-9193 KW - blaI gene KW - mecA gene KW - mecI gene KW - polysaccharides KW - receptor polysaccharides KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18774713?accountid=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=Coaggregation-Mediated+Interactions+of+Streptococci+and+Actinomyces+Detected+in+Initial+Human+Dental+Plaque&rft.au=Palmer%2C+RJ+Jr%3BGordon%2C+S+M%3BCisar%2C+JO%3BKolenbrander%2C+P+E%3BRosato%2C+A+E%3BCraig%2C+WA%3BArcher%2C+G+L&rft.aulast=Palmer&rft.aufirst=RJ&rft.date=2003-06-01&rft.volume=185&rft.issue=11&rft.spage=3400&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.185.11.3400-3409.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.185.11.3400-3409.2003 ER - TY - JOUR T1 - Escherichia coli SspA is a transcription activator for bacteriophage P1 late genes AN - 18770588; 5641284 AB - The stringent starvation protein A (SspA), an Escherichia coli RNA polymerase (RNAP)-associated protein, has been reported to be essential for lytic growth of bacteriophage P1. Unlike P1 early promoters, P1 late promoters are not recognized by RNAP alone. A phage-encoded early protein, Lpa (late promoter activator protein, formerly called gp10), has been shown to be required for P1 late transcription in vivo. Here, we demonstrate that SspA is a transcription activator for P1 late genes. Our results indicated that Lpa is not limiting in an sspA mutant. However, the transcription of P1 late genes was deficient in an sspA mutant in vivo. We demonstrated that SspA/Lpa are required for transcription activation of the P1 late promoter Ps in vitro. In addition, SspA and Lpa were shown to facilitate the binding of RNAP to Ps late promoter DNA. Activation of late transcription by SspA/Lpa was dependent on holoenzyme containing sigma super(70) but not sigma super(S), indicating that the two activators discriminate between the two forms of the holoenzyme. Furthermore, P1 early gene expression was downregulated in the wild-type background, whereas it persisted in the sspA mutant background, indicating that SspA/Lpa mediate the transcriptional switch from the early to the late genes during P1 lytic growth. Thus, this work provides the first evidence for a function of the E. coli RNAP-associated protein SspA. JF - Molecular Microbiology AU - Hansen, A AU - Lehnherr, H AU - Wang, X AU - Mobley, V AU - Jin, D J AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 37 Convent Drive, 9000 Rockville Pike, Bethesda, MD 20892-4264, USA. Department of Biochemistry and Molecular Biology, University of Southern Denmark-Odense University, Campusvej 55, DK-5230 Odense M, Denmark., djjin@helix.nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 1621 EP - 1631 PB - Blackwell Science Ltd VL - 48 IS - 6 SN - 0950-382X, 0950-382X KW - Lpa protein KW - SspA protein KW - sigma 70 Factor KW - sigma 70 factor KW - sigma S Factor KW - sigma S factor KW - Biochemistry Abstracts 2: Nucleic Acids; Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - J 02726:RNA and ribosomes KW - N 14930:Transcription factors KW - G 07320:Bacterial genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18770588?accountid=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=Escherichia+coli+SspA+is+a+transcription+activator+for+bacteriophage+P1+late+genes&rft.au=Hansen%2C+A%3BLehnherr%2C+H%3BWang%2C+X%3BMobley%2C+V%3BJin%2C+D+J&rft.aulast=Hansen&rft.aufirst=A&rft.date=2003-06-01&rft.volume=48&rft.issue=6&rft.spage=1621&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2003.03533.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2003.03533.x ER - TY - JOUR T1 - Ribosome-DnaK interactions in relation to protein folding AN - 18767315; 5641288 AB - Bacterial ribosomes or their 50S subunit can refold many unfolded proteins. The folding activity resides in domain V of 23S RNA of the 50S subunit. Here we show that ribosomes can also refold a denatured chaperone, DnaK, in vitro, and the activity may apply in the folding of nascent DnaK polypeptides in vivo. The chaperone was unusual as the native protein associated with the 50S subunit stably with a 1:1 stoichiometry in vitro. The binding site of the native protein appears to be different from the domain V of 23S RNA, the region with which denatured proteins interact. The DnaK binding influenced the protein folding activity of domain V modestly. Conversely, denatured protein binding to domain V led to dissociation of the native chaperone from the 50S subunit. DnaK thus appears to depend on ribosomes for its own folding, and upon folding, can rebind to ribosome to modulate its general protein folding activity. JF - Molecular Microbiology AU - Ghosh, J AU - Basu, A AU - Pal, S AU - Chowdhuri, S AU - Bhattacharya, A AU - Pal, D AU - Chattoraj, D K AU - Dasgupta, C AD - Department of Biophysics, Molecular Biology and Genetics, University of Calcutta, 92 A. P. C. Road, Calcutta, India., chattoraj@nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 1679 EP - 1692 PB - Blackwell Science Ltd VL - 48 IS - 6 SN - 0950-382X, 0950-382X KW - DnaK protein KW - rRNA 23S KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02726:RNA and ribosomes KW - N 14413:Biological properties, including effects of antibiotics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18767315?accountid=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=Ribosome-DnaK+interactions+in+relation+to+protein+folding&rft.au=Ghosh%2C+J%3BBasu%2C+A%3BPal%2C+S%3BChowdhuri%2C+S%3BBhattacharya%2C+A%3BPal%2C+D%3BChattoraj%2C+D+K%3BDasgupta%2C+C&rft.aulast=Ghosh&rft.aufirst=J&rft.date=2003-06-01&rft.volume=48&rft.issue=6&rft.spage=1679&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2003.03538.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2003.03538.x ER - TY - JOUR T1 - Dentate Gyrus: Alterations that Occur with Hippocampal Injury AN - 18766768; 5638418 AB - Injury to the brain usually manifests not in a diffuse uniform manner but rather with selective sites of damage indicative of differential vulnerability. This question of neuronal susceptibility has been one of major interest both in disease processes as well as damage induced by environmental factors. For experimental examination, brain structures with obvious neuronal subpopulations and organization such as the cerebellum and the hippocampus have offered the most promise. In the hippocampus distinct neuronal populations exist that demonstrate differential vulnerability to various forms of insult including ischemia, excitotoxicity, and environmental factors. The more recent data regarding the presence of neuronal progenitor cells in the subgranular zone of the dentate offers the opportunity to expand such experimental examination to the process of injury-induced neurogenesis. Thus, more recent studies have expanded the examination of the hippocampus to include models of damage to the dentate neurons in addition to the highly vulnerable pyramidal neurons. A number of these models are presented for both human disease and experimental animal conditions. Examination of the responses between these distinct cell populations offers the potential for understanding factors that are critical in neuronal death and survival. JF - Neurotoxicology AU - Harry, G J AU - D'Hellencourt, CL AD - Neurotoxicology Group, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, harry@niehs.nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 343 EP - 356 VL - 24 IS - 3 SN - 0161-813X, 0161-813X KW - injury KW - man KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11104:Mammals (except primates) KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18766768?accountid=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=Neurotoxicology&rft.atitle=Dentate+Gyrus%3A+Alterations+that+Occur+with+Hippocampal+Injury&rft.au=Harry%2C+G+J%3BD%27Hellencourt%2C+CL&rft.aulast=Harry&rft.aufirst=G&rft.date=2003-06-01&rft.volume=24&rft.issue=3&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/10.1016%2FS0161-813X%2803%2900039-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0161-813X(03)00039-1 ER - TY - JOUR T1 - UV-induced DNA damage and melanin content in human skin differing in racial/ethnic origin AN - 17130299; 6775077 AB - DNA damage induced by UV radiation is a critical event in skin photocarcinogenesis, but the role of racial/ethnic origin in determining individual UV sensitivity remains unclear. This study examined the relationships between melanin content, its changes, and DNA damage induced in situ in normal human skin of different racial/ethnic groups, phototypes, and UV sensitivities after exposure to a relatively low UV dose of less than or equal to 1 minimal erythema dose (MED). JF - FASEB Journal AU - Tadokoro, Taketsugu AU - Kobayashi, Nobuhiko AU - Zmudzka, Barbara Z AU - Ito, Shosuke AU - Wakamatsu, Kazumasa AU - Yamaguchi, Yuji AU - Korossy, Katalin S AU - Miller, Sharon A AU - Beer, Janusz Z AU - Hearing, Vincent J AD - Laboratory of Cell Biology, Building 37, Room 1B25, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, hearingv@nih.gov Y1 - 2003/06// PY - 2003 DA - Jun 2003 SP - 1177 EP - 1179 PB - Federation of American Societies for Experimental Biology VL - 17 IS - 9 SN - 0892-6638, 0892-6638 KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - DNA damage KW - Melanin KW - Erythema KW - Skin KW - U.V. radiation KW - Ethnic groups KW - X 24210:Radiation & radioactive materials KW - N 14035:DNA: Direct modification or damage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17130299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FASEB+Journal&rft.atitle=UV-induced+DNA+damage+and+melanin+content+in+human+skin+differing+in+racial%2Fethnic+origin&rft.au=Tadokoro%2C+Taketsugu%3BKobayashi%2C+Nobuhiko%3BZmudzka%2C+Barbara+Z%3BIto%2C+Shosuke%3BWakamatsu%2C+Kazumasa%3BYamaguchi%2C+Yuji%3BKorossy%2C+Katalin+S%3BMiller%2C+Sharon+A%3BBeer%2C+Janusz+Z%3BHearing%2C+Vincent+J&rft.aulast=Tadokoro&rft.aufirst=Taketsugu&rft.date=2003-06-01&rft.volume=17&rft.issue=9&rft.spage=1177&rft.isbn=&rft.btitle=&rft.title=FASEB+Journal&rft.issn=08926638&rft_id=info:doi/10.1096%2Ffj.02-0865fje LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-10-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - DNA damage; Erythema; Melanin; U.V. radiation; Skin; Ethnic groups DO - http://dx.doi.org/10.1096/fj.02-0865fje ER - TY - JOUR T1 - Regulatory role of arginine 204 in the catalytic activity of rat alloantigens ART2a and ART2b. AN - 73291119; 12649291 AB - ART2a (RT6.1) and ART2b (RT6.2) are NAD glycohydrolases (NADases) that are linked to T lymphocytes by glycosylphosphatidylinositol anchors. Although both mature proteins possess three conserved regions (I, II, III) that form the NAD-binding site and differ by only ten amino acids, only ART2b is auto-ADP-ribosylated and only ART2a is glycosylated. To investigate the structural basis for these differences, wild-type and mutant ART2a and ART2b were expressed in rat mammary adenocarcinoma (NMU) cells and released with phosphatidylinositol-specific phospholipase C. All mutants were immunoreactive NADases. Arginine 204 (Arg204), NH2-terminal to essential glutamate 209 in Region III, is found in ART2b, but not ART2a. Replacement of Arg204 in ART2b with lysine, tyrosine, or glutamate abolished auto-ADP-ribosylation. Unlike wild-type ART2a, ART2a(Y204R) was auto-ADP-ribosylated. The tryptophan mutant ART2b(R204W) was auto-ADP-ribosylated and exhibited enhanced NADase activity. Incubation with NAD and auto-ADP-ribosylation decreased the NADase activities of wild-type ART2b and ART2b (R204W), whereas activity of ART2b(R204K), which is not auto-modified, was unchanged by NAD. Facilitation of auto-ADP-ribosylation by tryptophan 204 suggests that the hydrophobic amino acid mimics an ADP-ribosylated arginine. Thus, Arg204 in ART2b serves as a regulatory switch whose presence is required for additional auto-ADP-ribosylation and regulation of catalytic activity. JF - The Journal of biological chemistry AU - Stevens, Linda A AU - Bourgeois, Christelle AU - Bortell, Rita AU - Moss, Joel AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1590, USA. stevensl@nhlbi.nih.gov Y1 - 2003/05/30/ PY - 2003 DA - 2003 May 30 SP - 19591 EP - 19596 VL - 278 IS - 22 SN - 0021-9258, 0021-9258 KW - Antigens, Differentiation, T-Lymphocyte KW - 0 KW - DNA Primers KW - Membrane Glycoproteins KW - Arginine KW - 94ZLA3W45F KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - Art2b protein, rat KW - EC 2.4.2.31 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Kinetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Cell Line KW - Catalysis KW - Membrane Glycoproteins -- chemistry KW - ADP Ribose Transferases -- chemistry KW - Arginine -- metabolism KW - ADP Ribose Transferases -- metabolism KW - Membrane Glycoproteins -- metabolism KW - Membrane Glycoproteins -- genetics KW - ADP Ribose Transferases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73291119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulatory+role+of+arginine+204+in+the+catalytic+activity+of+rat+alloantigens+ART2a+and+ART2b.&rft.au=Stevens%2C+Linda+A%3BBourgeois%2C+Christelle%3BBortell%2C+Rita%3BMoss%2C+Joel&rft.aulast=Stevens&rft.aufirst=Linda&rft.date=2003-05-30&rft.volume=278&rft.issue=22&rft.spage=19591&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 - 2003-07-10 N1 - Date created - 2003-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypoxia-inducible factor and its biomedical relevance. AN - 73272318; 12639949 JF - The Journal of biological chemistry AU - Huang, L Eric AU - Bunn, H Franklin AD - Laboratory of Human Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. huange@mail.nih.gov Y1 - 2003/05/30/ PY - 2003 DA - 2003 May 30 SP - 19575 EP - 19578 VL - 278 IS - 22 SN - 0021-9258, 0021-9258 KW - Transcription Factors KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Protein Conformation KW - Transcription Factors -- physiology KW - Transcription Factors -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73272318?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hypoxia-inducible+factor+and+its+biomedical+relevance.&rft.au=Huang%2C+L+Eric%3BBunn%2C+H+Franklin&rft.aulast=Huang&rft.aufirst=L&rft.date=2003-05-30&rft.volume=278&rft.issue=22&rft.spage=19575&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 - 2003-07-10 N1 - Date created - 2003-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microarray analysis reveals induction of heat shock proteins mRNAs by the torsion dystonia protein, TorsinA. AN - 73303773; 12749984 AB - An in-frame deletion (Delta E302/303) in the TorsinA gene has been demonstrated to be responsible for primary torsion dystonia, showing dominant inheritance with reduced penetrance. The Delta E302/303 torsinA mutation forms intracellular ER derived inclusions in a variety of cultured cells, which may suggest that the mutations might evoke ER stress. We used microarray analysis of human derived cell lines expressing the Delta E302/303 torsinA mutation in order to reveal alterations in gene expression in the hope of identifying genetic modifying loci or novel markers for disease pathogenesis. We identified transcriptional changes in multiple members of the heat shock protein family of genes, confirmed by reverse transcription-polymerase chain reaction, which could be indicative of ER stress. However, both wild type and mutant torsinA were affected to a similar extent, suggesting that this is not related to either disease state or the formation of ER-derived inclusions. JF - Neuroscience letters AU - Baptista, Melisa J AU - O'Farrell, Casey AU - Hardy, John AU - Cookson, Mark R AD - Laboratory of Neurogenetics, National Institute on Aging/National Institutes of Health, 9000 Rockville Pike, Building 10, Room 6C103, MSC1589, 9000 Rockville Pike, Bethesda, MD 20892, USA. baptista@mail.nih.gov Y1 - 2003/05/29/ PY - 2003 DA - 2003 May 29 SP - 5 EP - 8 VL - 343 IS - 1 SN - 0304-3940, 0304-3940 KW - Carrier Proteins KW - 0 KW - Heat-Shock Proteins KW - Molecular Chaperones KW - RNA, Messenger KW - TOR1A protein, human KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Reference Values KW - Kidney -- metabolism KW - Transfection KW - Humans KW - Heat-Shock Response KW - Kidney -- embryology KW - Oligonucleotide Array Sequence Analysis -- methods KW - Reverse Transcriptase Polymerase Chain Reaction -- methods KW - Cloning, Molecular KW - Heat-Shock Proteins -- metabolism KW - Dystonia Musculorum Deformans -- metabolism KW - Carrier Proteins -- metabolism KW - RNA, Messenger -- metabolism KW - Carrier Proteins -- genetics KW - Gene Expression Regulation KW - RNA, Messenger -- genetics KW - Dystonia Musculorum Deformans -- genetics KW - Heat-Shock Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73303773?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Microarray+analysis+reveals+induction+of+heat+shock+proteins+mRNAs+by+the+torsion+dystonia+protein%2C+TorsinA.&rft.au=Baptista%2C+Melisa+J%3BO%27Farrell%2C+Casey%3BHardy%2C+John%3BCookson%2C+Mark+R&rft.aulast=Baptista&rft.aufirst=Melisa&rft.date=2003-05-29&rft.volume=343&rft.issue=1&rft.spage=5&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 - 2003-07-01 N1 - Date created - 2003-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Golgi-dependent transport of cholesterol to the Chlamydia trachomatis inclusion AN - 18771356; 5639441 AB - Cholesterol, a lipid not normally found in prokaryotes, was identified in purified Chlamydia trachomatis elementary bodies and in the chlamydial parasitophorous vacuole (inclusion) membrane of infected HeLa cells. Chlamydiae obtained eukaryotic host cell cholesterol both from de novo synthesis or low-density lipoprotein. Acquisition of either de novo-synthesized cholesterol or low-density lipoprotein-derived cholesterol was microtubule- dependent and brefeldin A-sensitive, indicating a requirement for the Golgi apparatus. Transport also required chlamydial protein synthesis, indicative of a pathogen-directed process. The cholesterol trafficking pathway appears to coincide with a previously characterized delivery of sphingomyelin to the inclusion in that similar pharmacological treatments inhibited transport of both sphingomyelin and cholesterol. These results support the hypothesis that sphingomyelin and cholesterol may be cotransported via a Golgi-dependent pathway and that the chlamydial inclusion receives cholesterol preferentially from a brefeldin A-sensitive pathway of cholesterol trafficking from the Golgi apparatus to the plasma membrane. JF - Proceedings of the National Academy of Sciences, USA AU - Carabeo, R A AU - Mead, D J AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health Rocky Mountain Laboratories, Hamilton, MT 59840, ted_hackstadt@nih.gov Y1 - 2003/05/27/ PY - 2003 DA - 2003 May 27 SP - 6771 EP - 6776 VL - 100 IS - 11 SN - 0027-8424, 0027-8424 KW - inclusion KW - sphingomyelin KW - Microbiology Abstracts B: Bacteriology KW - J 02731:Lipids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18771356?accountid=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=Golgi-dependent+transport+of+cholesterol+to+the+Chlamydia+trachomatis+inclusion&rft.au=Carabeo%2C+R+A%3BMead%2C+D+J%3BHackstadt%2C+T&rft.aulast=Carabeo&rft.aufirst=R&rft.date=2003-05-27&rft.volume=100&rft.issue=11&rft.spage=6771&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.1131289100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.1131289100 ER - TY - JOUR T1 - Roles of Src and epidermal growth factor receptor transactivation in transient and sustained ERK1/2 responses to gonadotropin-releasing hormone receptor activation. AN - 73315276; 12642580 AB - The duration as well as the magnitude of mitogen-activated protein kinase activation has been proposed to regulate gene expression and other specific intracellular responses in individual cell types. Activation of ERK1/2 by the hypothalamic neuropeptide gonadotropin-releasing hormone (GnRH) is relatively sustained in alpha T3-1 pituitary gonadotropes and HEK293 cells but is transient in immortalized GT1-7 neurons. Each of these cell types expresses the epidermal growth factor receptor (EGFR) and responds to EGF stimulation with significant but transient ERK1/2 phosphorylation. However, GnRH-induced ERK1/2 phosphorylation caused by EGFR transactivation was confined to GT1-7 cells and was attenuated by EGFR kinase inhibition. Neither EGF nor GnRH receptor activation caused translocation of phospho-ERK1/2 into the nucleus in GT1-7 cells. In contrast, agonist stimulation of GnRH receptors expressed in HEK293 cells caused sustained phosphorylation and nuclear translocation of ERK1/2 by a protein kinase C-dependent but EGFR-independent pathway. GnRH-induced activation of ERK1/2 was attenuated by the selective Src kinase inhibitor PP2 and the negative regulatory C-terminal Src kinase in GT1-7 cells but not in HEK293 cells. In GT1-7 cells, GnRH stimulated phosphorylation and nuclear translocation of the ERK1/2-dependent protein, p90RSK-1 (RSK-1). These results indicate that the duration of ERK1/2 activation depends on the signaling pathways utilized by GnRH in specific target cells. Whereas activation of the Gq/protein kinase C pathway in HEK293 cells causes sustained phosphorylation and translocation of ERK1/2 to the nucleus, transactivation of the EGFR by GnRH in GT1-7 cells elicits transient ERK1/2 signals without nuclear accumulation. These findings suggest that transactivation of the tightly regulated EGFR can account for the transient ERK1/2 responses that are elicited by stimulation of certain G protein-coupled receptors. JF - The Journal of biological chemistry AU - Shah, Bukhtiar H AU - Farshori, M Parvaiz AU - Jambusaria, Anokhi AU - Catt, Kevin J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4510, USA. Y1 - 2003/05/23/ PY - 2003 DA - 2003 May 23 SP - 19118 EP - 19126 VL - 278 IS - 21 SN - 0021-9258, 0021-9258 KW - Inositol Phosphates KW - 0 KW - Receptors, LHRH KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - src-Family Kinases KW - EC 2.7.10.2 KW - Ribosomal Protein S6 Kinases, 90-kDa KW - EC 2.7.11.1 KW - Rps6ka1 protein, mouse KW - Protein Kinase C KW - EC 2.7.11.13 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Immunoblotting KW - Hypothalamus KW - Cell Nucleus -- metabolism KW - Biological Transport KW - Gene Expression KW - Mice KW - Genes, fos -- genetics KW - Protein Kinase C -- metabolism KW - Ribosomal Protein S6 Kinases, 90-kDa -- metabolism KW - Phosphorylation KW - Transfection KW - Inositol Phosphates -- analysis KW - Neurons KW - Enzyme Activation -- drug effects KW - Tetradecanoylphorbol Acetate -- administration & dosage KW - Cell Line, Transformed KW - Gonadotropin-Releasing Hormone -- pharmacology KW - Immunohistochemistry KW - Signal Transduction KW - Cell Line KW - src-Family Kinases -- genetics KW - Receptors, LHRH -- physiology KW - Receptors, LHRH -- drug effects KW - Receptor, Epidermal Growth Factor -- genetics KW - Mitogen-Activated Protein Kinases -- metabolism KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Receptors, LHRH -- genetics KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73315276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Roles+of+Src+and+epidermal+growth+factor+receptor+transactivation+in+transient+and+sustained+ERK1%2F2+responses+to+gonadotropin-releasing+hormone+receptor+activation.&rft.au=Shah%2C+Bukhtiar+H%3BFarshori%2C+M+Parvaiz%3BJambusaria%2C+Anokhi%3BCatt%2C+Kevin+J&rft.aulast=Shah&rft.aufirst=Bukhtiar&rft.date=2003-05-23&rft.volume=278&rft.issue=21&rft.spage=19118&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 - 2003-07-07 N1 - Date created - 2003-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Palmitoylation regulates regulators of G-protein signaling (RGS) 16 function. I. Mutation of amino-terminal cysteine residues on RGS16 prevents its targeting to lipid rafts and palmitoylation of an internal cysteine residue. AN - 73293538; 12642593 AB - Regulators of G-protein signaling (RGS) proteins down-regulate signaling by heterotrimeric G-proteins by accelerating GTP hydrolysis on the G alpha subunits. Palmitoylation, the reversible addition of palmitate to cysteine residues, occurs on several RGS proteins and is critical for their activity. For RGS16, mutation of Cys-2 and Cys-12 blocks its incorporation of [3H]palmitate and ability to turn-off Gi and Gq signaling and significantly inhibited its GTPase activating protein activity toward aG alpha subunit fused to the 5-hydroxytryptamine receptor 1A, but did not reduce its plasma membrane localization based on cell fractionation studies and immunoelectron microscopy. Palmitoylation can target proteins, including many signaling proteins, to membrane microdomains, called lipid rafts. A subpopulation of endogenous RGS16 in rat liver membranes and overexpressed RGS16 in COS cells, but not the nonpalmitoylated cysteine mutant of RGS16, localized to lipid rafts. However, disruption of lipid rafts by treatment with methyl-beta-cyclodextrin did not decrease the GTPase activating protein activity of RGS16. The lipid raft fractions were enriched in protein acyltransferase activity, and RGS16 incorporated [3H]palmitate into a peptide fragment containing Cys-98, a highly conserved cysteine within the RGS box. These results suggest that the amino-terminal palmitoylation of an RGS protein promotes its lipid raft targeting that allows palmitoylation of a poorly accessible cysteine residue that we show in the accompanying article (Osterhout, J. L., Waheed, A. A., Hiol, A., Ward, R. J., Davey, P. C., Nini, L., Wang, J., Milligan, G., Jones, T. L. Z., and Druey, K. M. (2003) J. Biol. Chem. 278, 19309-19316) was critical for RGS16 and RGS4 GAP activity. JF - The Journal of biological chemistry AU - Hiol, Abel AU - Davey, Penelope C AU - Osterhout, James L AU - Waheed, Abdul A AU - Fischer, Elizabeth R AU - Chen, Ching-Kang AU - Milligan, Graeme AU - Druey, Kirk M AU - Jones, Teresa L Z AD - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/05/23/ PY - 2003 DA - 2003 May 23 SP - 19301 EP - 19308 VL - 278 IS - 21 SN - 0021-9258, 0021-9258 KW - Caveolin 1 KW - 0 KW - Caveolins KW - Cyclodextrins KW - Membrane Lipids KW - Proteins KW - RGS Proteins KW - RGS16 protein KW - Receptors, Serotonin KW - Receptors, Serotonin, 5-HT1 KW - Recombinant Fusion Proteins KW - beta-Cyclodextrins KW - methyl-beta-cyclodextrin KW - Palmitic Acid KW - 2V16EO95H1 KW - Serotonin KW - 333DO1RDJY KW - Guanosine Triphosphate KW - 86-01-1 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - GTP-Binding Protein alpha Subunits, Gi-Go KW - EC 3.6.5.1 KW - Heterotrimeric GTP-Binding Proteins KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - GTP-Binding Protein alpha Subunits, Gi-Go -- metabolism KW - COS Cells KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Heterotrimeric GTP-Binding Proteins -- genetics KW - Mutagenesis KW - Guanosine Triphosphate -- metabolism KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Liver -- ultrastructure KW - Cyclodextrins -- pharmacology KW - Enzyme Activation -- drug effects KW - Cell Membrane -- chemistry KW - Microscopy, Immunoelectron KW - Receptors, Serotonin -- genetics KW - Male KW - Molecular Structure KW - GTP-Binding Protein alpha Subunits, Gi-Go -- analysis KW - Serotonin -- pharmacology KW - Immunoblotting KW - Cysteine -- metabolism KW - Models, Molecular KW - Glutathione Transferase -- genetics KW - Mice KW - Caveolins -- analysis KW - Membrane Lipids -- analysis KW - Transfection KW - GTP Phosphohydrolases -- metabolism KW - Cell Line KW - RGS Proteins -- genetics KW - Proteins -- chemistry KW - RGS Proteins -- physiology KW - RGS Proteins -- chemistry KW - Proteins -- genetics KW - Palmitic Acid -- metabolism KW - Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73293538?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Palmitoylation+regulates+regulators+of+G-protein+signaling+%28RGS%29+16+function.+I.+Mutation+of+amino-terminal+cysteine+residues+on+RGS16+prevents+its+targeting+to+lipid+rafts+and+palmitoylation+of+an+internal+cysteine+residue.&rft.au=Hiol%2C+Abel%3BDavey%2C+Penelope+C%3BOsterhout%2C+James+L%3BWaheed%2C+Abdul+A%3BFischer%2C+Elizabeth+R%3BChen%2C+Ching-Kang%3BMilligan%2C+Graeme%3BDruey%2C+Kirk+M%3BJones%2C+Teresa+L+Z&rft.aulast=Hiol&rft.aufirst=Abel&rft.date=2003-05-23&rft.volume=278&rft.issue=21&rft.spage=19301&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 - 2003-07-07 N1 - Date created - 2003-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphospecific site tyrosine phosphorylation of p125FAK and proline-rich kinase 2 is differentially regulated by cholecystokinin receptor type A activation in pancreatic acini. AN - 73286838; 12651850 AB - The focal adhesion kinases, p125FAK and proline-rich kinase 2 (PYK2), are involved in numerous processes as adhesion, cytoskeletal changes, and growth. These kinases have 45% homology and share three tyrosine phosphorylation (TyrP) sites. Little information exists on the ability of stimulants to cause TyrP of each kinase site and the cellular mechanism involved. We explored the ability of the neurotransmitter/hormone, CCK, to stimulate TyrP at each site. In rat pancreatic acini, CCK stimulated TyrP at each site in both kinases. TyrP was rapid except for pY397FAK. The magnitude of TyrP differed with the different FAK and PYK2 sites. The CCK dose-response curve for TyrP for sites in each kinase was similar. CCK-JMV, an agonist of the high affinity receptor state and antagonist of the low affinity receptor state, was less efficacious than CCK at each FAK/PYK2 site and inhibited CCK maximal stimulation. Thapsigargin decreased CCK-stimulated TyrP of pY402PYK2 and pY925FAK but not the other sites. GF109203X reduced TyrP of only the PYK2 sites, pY402 and pY580. GF109203X with thapsigargin decreased TyrP of pY402PYK2 and the three FAK sites more than either inhibitor alone. Basal TyrP of pY397FAK was greater than other sites. These results demonstrate that CCK stimulates tyrosine phosphorylation of each of the three homologous phosphorylation sites in FAK and PYK2. However, CCK-stimulated TyrP at these sites differs in kinetics, magnitude, and participation of the high/low affinity receptor states and by protein kinase C and [Ca2+]i. These results show that phosphorylation of these different sites is differentially regulated and involves different intracellular mechanisms in the same cell. JF - The Journal of biological chemistry AU - Pace, Andrea AU - García-Marin, Luis J AU - Tapia, Jose A AU - Bragado, María J AU - Jensen, Robert T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/05/23/ PY - 2003 DA - 2003 May 23 SP - 19008 EP - 19016 VL - 278 IS - 21 SN - 0021-9258, 0021-9258 KW - Diglycerides KW - 0 KW - Enzyme Inhibitors KW - Indoles KW - Inositol Phosphates KW - Maleimides KW - Phosphatidylinositol 4,5-Diphosphate KW - Receptors, Cholecystokinin KW - Phosphotyrosine KW - 21820-51-9 KW - Thapsigargin KW - 67526-95-8 KW - Cholecystokinin KW - 9011-97-6 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Focal Adhesion Kinase 1 KW - EC 2.7.10.2 KW - Focal Adhesion Kinase 2 KW - Focal Adhesion Protein-Tyrosine Kinases KW - Ptk2 protein, rat KW - Ptk2b protein, rat KW - Protein Kinase C KW - EC 2.7.11.13 KW - Type C Phospholipases KW - EC 3.1.4.- KW - bisindolylmaleimide I KW - L79H6N0V6C KW - Sincalide KW - M03GIQ7Z6P KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Inositol Phosphates -- metabolism KW - Sincalide -- pharmacology KW - Type C Phospholipases -- metabolism KW - Calcium -- metabolism KW - Rats KW - Phosphorylation KW - Cholecystokinin -- pharmacology KW - Phosphatidylinositol 4,5-Diphosphate -- metabolism KW - Male KW - Maleimides -- pharmacology KW - Enzyme Activation KW - Dose-Response Relationship, Drug KW - Hydrolysis KW - Binding Sites KW - Thapsigargin -- pharmacology KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Rats, Sprague-Dawley KW - Cholecystokinin -- administration & dosage KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Indoles -- pharmacology KW - Diglycerides -- metabolism KW - Phosphotyrosine -- metabolism KW - Receptors, Cholecystokinin -- physiology KW - Protein-Tyrosine Kinases -- metabolism KW - Pancreas -- enzymology KW - Protein-Tyrosine Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73286838?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phosphospecific+site+tyrosine+phosphorylation+of+p125FAK+and+proline-rich+kinase+2+is+differentially+regulated+by+cholecystokinin+receptor+type+A+activation+in+pancreatic+acini.&rft.au=Pace%2C+Andrea%3BGarc%C3%ADa-Marin%2C+Luis+J%3BTapia%2C+Jose+A%3BBragado%2C+Mar%C3%ADa+J%3BJensen%2C+Robert+T&rft.aulast=Pace&rft.aufirst=Andrea&rft.date=2003-05-23&rft.volume=278&rft.issue=21&rft.spage=19008&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 - 2003-07-07 N1 - Date created - 2003-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Palmitoylation regulates regulator of G-protein signaling (RGS) 16 function. II. Palmitoylation of a cysteine residue in the RGS box is critical for RGS16 GTPase accelerating activity and regulation of Gi-coupled signalling. AN - 73277927; 12642592 AB - Palmitoylation is a reversible post-translational modification used by cells to regulate protein activity. The regulator of G-protein signaling (RGS) proteins RGS4 and RGS16 share conserved cysteine (Cys) residues that undergo palmitoylation. In the accompanying article (Hiol, A., Davey, P. C., Osterhout, J. L., Waheed, A. A., Fischer, E. R., Chen, C. K., Milligan, G., Druey, K. M., and Jones, T. L. Z. (2003) J. Biol. Chem. 278, 19301-19308), we determined that mutation of NH2-terminal cysteine residues in RGS16 (Cys-2 and Cys-12) reduced GTPase accelerating (GAP) activity toward a 5-hydroxytryptamine (5-HT1A)/G alpha o1 receptor fusion protein in cell membranes. NH2-terminal acylation also permitted palmitoylation of a cysteine residue in the RGS box of RGS16 (Cys-98). Here we investigated the role of internal palmitoylation in RGS16 localization and GAP activity. Mutation of RGS16 Cys-98 or RGS4 Cys-95 to alanine reduced GAP activity on the 5-HT1A/G alpha o1 fusion protein and regulation of adenylyl cyclase inhibition. The C98A mutation had no effect on RGS16 localization or GAP activity toward purified G-protein alpha subunits. Enzymatic palmitoylation of RGS16 resulted in internal palmitoylation on residue Cys-98. Palmitoylated RGS16 or RGS4 WT but not C98A or C95A preincubated with membranes expressing 5-HT1a/G alpha o1 displayed increased GAP activity over time. These results suggest that palmitoylation of a Cys residue in the RGS box is critical for RGS16 and RGS4 GAP activity and their ability to regulate Gi-coupled signaling in mammalian cells. JF - The Journal of biological chemistry AU - Osterhout, James L AU - Waheed, Abdul A AU - Hiol, Abel AU - Ward, Richard J AU - Davey, Penelope C AU - Nini, Lylia AU - Wang, Jiun AU - Milligan, Graeme AU - Jones, Teresa L Z AU - Druey, Kirk M AD - Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20892, USA. Y1 - 2003/05/23/ PY - 2003 DA - 2003 May 23 SP - 19309 EP - 19316 VL - 278 IS - 21 SN - 0021-9258, 0021-9258 KW - Adenylyl Cyclase Inhibitors KW - 0 KW - Caveolin 1 KW - Caveolins KW - GTPase-Activating Proteins KW - Membrane Lipids KW - Proteins KW - RGS Proteins KW - RGS16 protein KW - Recombinant Fusion Proteins KW - RGS4 protein KW - 175335-35-0 KW - Palmitic Acid KW - 2V16EO95H1 KW - Somatostatin KW - 51110-01-1 KW - Pertussis Toxin KW - EC 2.4.2.31 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - GTP-Binding Protein alpha Subunits, Gi-Go KW - EC 3.6.5.1 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - COS Cells KW - Cell Membrane -- enzymology KW - Models, Molecular KW - Humans KW - Recombinant Fusion Proteins -- isolation & purification KW - Pertussis Toxin -- pharmacology KW - Escherichia coli -- chemistry KW - Mice KW - Caveolins -- analysis KW - Structure-Activity Relationship KW - Mutagenesis KW - Binding Sites KW - Somatostatin -- pharmacology KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Membrane Lipids -- analysis KW - Transfection KW - GTPase-Activating Proteins -- physiology KW - Cell Membrane -- chemistry KW - Cell Line KW - GTP-Binding Protein alpha Subunits, Gi-Go -- analysis KW - Cysteine -- metabolism KW - RGS Proteins -- physiology KW - RGS Proteins -- analysis KW - Palmitic Acid -- metabolism KW - Proteins -- genetics KW - Proteins -- physiology KW - GTP-Binding Protein alpha Subunits, Gi-Go -- physiology KW - RGS Proteins -- genetics KW - GTP Phosphohydrolases -- metabolism KW - Proteins -- analysis KW - RGS Proteins -- chemistry KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73277927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Palmitoylation+regulates+regulator+of+G-protein+signaling+%28RGS%29+16+function.+II.+Palmitoylation+of+a+cysteine+residue+in+the+RGS+box+is+critical+for+RGS16+GTPase+accelerating+activity+and+regulation+of+Gi-coupled+signalling.&rft.au=Osterhout%2C+James+L%3BWaheed%2C+Abdul+A%3BHiol%2C+Abel%3BWard%2C+Richard+J%3BDavey%2C+Penelope+C%3BNini%2C+Lylia%3BWang%2C+Jiun%3BMilligan%2C+Graeme%3BJones%2C+Teresa+L+Z%3BDruey%2C+Kirk+M&rft.aulast=Osterhout&rft.aufirst=James&rft.date=2003-05-23&rft.volume=278&rft.issue=21&rft.spage=19309&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 - 2003-07-07 N1 - Date created - 2003-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural determinants in human DNA polymerase gamma account for mitochondrial toxicity from nucleoside analogs. AN - 73270880; 12742017 AB - Although antiviral nucleoside analog therapy successfully delays progression of HIV infection to AIDS, these drugs cause unwelcome side-effects by inducing mitochondrial toxicity. We and others have demonstrated that the mitochondrial polymerase, DNA polymerase gamma (pol gamma), participates in mitochondrial toxicity by incorporating these chain-terminating antiviral nucleotide analogs into DNA. Here, we explore the role of three highly conserved amino acid residues in the active site of human pol gamma that modulate selection of nucleotide analogs as substrates for incorporation. Sequence alignments, crystal structures and mutagenesis studies of family A DNA polymerases led us to change Tyr951 and Tyr955 in polymerase motif B to Phe and Ala, and Glu895 in polymerase motif A was changed to Ala. The mutant polymerases were tested for their ability to incorporate natural nucleotides and the five antiviral nucleoside analogs currently approved for antiviral therapy: AZT, ddC, D4T, 3TC and carbovir. Steady-state kinetic analysis of the pol gamma derivatives with the normal and antiviral nucleotides demonstrated that Tyr951 is largely responsible for the ability of pol gamma to incorporate dideoxynucleotides and D4T-MP. Mutation of Tyr951 to Phe renders the enzyme resistant to dideoxynucleotides and D4T-TP without compromising the activity of the polymerase. Alteration of Glu895 and Tyr955 to Ala had the largest effect on overall polymerase activity with normal nucleotides, producing dramatic increases in K(m(dNTP)) and large decreases in k(cat). Mutation of Tyr955 in pol gamma causes the degenerative disease progressive external ophthalmoplegia in humans, and we show that this residue partially accounts for the ability of pol gamma to incorporate D4T-MP and carbovir. Alteration of Glu895 to Ala slightly increased discrimination against dideoxynucleotides and D4T-TP. The mechanisms by which pol gamma selects certain nucleotide analogs are discussed. JF - Journal of molecular biology AU - Lim, Susan E AU - Ponamarev, Mikhail V AU - Longley, Matthew J AU - Copeland, William C AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2003/05/23/ PY - 2003 DA - 2003 May 23 SP - 45 EP - 57 VL - 329 IS - 1 SN - 0022-2836, 0022-2836 KW - Anti-HIV Agents KW - 0 KW - DNA Primers KW - DNA, Viral KW - Recombinant Fusion Proteins KW - Reverse Transcriptase Inhibitors KW - Lamivudine KW - 2T8Q726O95 KW - Zidovudine KW - 4B9XT59T7S KW - Zalcitabine KW - 6L3XT8CB3I KW - Stavudine KW - BO9LE4QFZF KW - DNA polymerase gamma KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Stavudine -- toxicity KW - Humans KW - Electrophoretic Mobility Shift Assay KW - Amino Acid Sequence KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Baculoviridae -- genetics KW - Lamivudine -- toxicity KW - Polymerase Chain Reaction KW - Zidovudine -- toxicity KW - DNA, Viral -- adverse effects KW - Protein Folding KW - Molecular Sequence Data KW - Zalcitabine -- toxicity KW - Sequence Homology, Amino Acid KW - Protein Conformation KW - DNA Primers -- chemistry KW - DNA, Viral -- metabolism KW - Anti-HIV Agents -- toxicity KW - Anti-HIV Agents -- metabolism KW - Mitochondria -- enzymology KW - Mitochondria -- drug effects KW - Reverse Transcriptase Inhibitors -- toxicity KW - DNA-Directed DNA Polymerase -- genetics KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73270880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Structural+determinants+in+human+DNA+polymerase+gamma+account+for+mitochondrial+toxicity+from+nucleoside+analogs.&rft.au=Lim%2C+Susan+E%3BPonamarev%2C+Mikhail+V%3BLongley%2C+Matthew+J%3BCopeland%2C+William+C&rft.aulast=Lim&rft.aufirst=Susan&rft.date=2003-05-23&rft.volume=329&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-19 N1 - Date created - 2003-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Accessing opiate dependence treatment medications: buprenorphine products in an office-based setting. AN - 73288592; 12738354 JF - Drug and alcohol dependence AU - Leshner, Alan I AD - National Institute on Drug Abuse, Bethesda 20892, MD, USA. aleshner@aaas.org Y1 - 2003/05/21/ PY - 2003 DA - 2003 May 21 SP - S103 EP - S104 VL - 70 IS - 2 Suppl KW - Buprenorphine, Naloxone Drug Combination KW - 0 KW - Drug Combinations KW - Narcotic Antagonists KW - Naloxone KW - 36B82AMQ7N KW - Buprenorphine KW - 40D3SCR4GZ KW - Index Medicus KW - Humans KW - Naloxone -- therapeutic use KW - Naloxone -- adverse effects KW - Opioid-Related Disorders -- diagnosis KW - Buprenorphine -- therapeutic use KW - Office Visits -- trends KW - Narcotic Antagonists -- therapeutic use KW - Narcotic Antagonists -- adverse effects KW - Buprenorphine -- adverse effects KW - Opioid-Related Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73288592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Accessing+opiate+dependence+treatment+medications%3A+buprenorphine+products+in+an+office-based+setting.&rft.au=Leshner%2C+Alan+I&rft.aulast=Leshner&rft.aufirst=Alan&rft.date=2003-05-21&rft.volume=70&rft.issue=2+Suppl&rft.spage=S103&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=1879-0046&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2009-10-14 N1 - Date created - 2003-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety and health policy considerations related to the use of buprenorphine/naloxone as an office-based treatment for opiate dependence. AN - 73261002; 12738352 AB - Opiate dependence remains a fundamental challenge confronting health delivery systems and is often characterized as a social and moral issue. The impact of this disorder on healthcare policy is changing with the increased incidence of HIV, hepatitis C, and tuberculosis infections in opiate-dependent patients. These medical illnesses have substantial effect on escalating healthcare costs, and, therefore, also affect healthcare policy priorities, which are responsive to these costs. Pharmacological treatments for opiate dependence have had limited success; often the consequence of limited access to care. Hence, there is a need to develop new pharmacotherapies for opiate dependence that extend the range of clinical options, including new first-line treatment approaches. This paper will focus on the safety and health policy considerations related to the use of buprenorphine and buprenorphine/naloxone based on data derived from clinical trials and post-marketing surveillance that provide evidence for the use of the medications as first-line treatments in an office-based environment. The evaluation of this evidence formed the basis by the National Institute on Drug Abuse to support and pursue the evaluation and registration of buprenorphine/naloxone and buprenorphine in a public/private sector cooperative effort to become an office-based, first-line treatment for opiate dependence. JF - Drug and alcohol dependence AU - Bridge, T Peter AU - Fudala, Paul J AU - Herbert, Susan AU - Leiderman, Deborah B AD - Division of Treatment Research and Development, National Institute on Drug Abuse, Bethesda, MD 20892, USA. pbridge@ix.netcom.com Y1 - 2003/05/21/ PY - 2003 DA - 2003 May 21 SP - S79 EP - S85 VL - 70 IS - 2 Suppl KW - Buprenorphine, Naloxone Drug Combination KW - 0 KW - Drug Combinations KW - Narcotic Antagonists KW - Naloxone KW - 36B82AMQ7N KW - Buprenorphine KW - 40D3SCR4GZ KW - Index Medicus KW - Humans KW - Treatment Outcome KW - Clinical Trials as Topic -- trends KW - Clinical Trials as Topic -- methods KW - Clinical Trials as Topic -- legislation & jurisprudence KW - Narcotic Antagonists -- administration & dosage KW - Naloxone -- administration & dosage KW - Opioid-Related Disorders -- epidemiology KW - Office Visits -- trends KW - Narcotic Antagonists -- adverse effects KW - Buprenorphine -- administration & dosage KW - Health Policy -- legislation & jurisprudence KW - Buprenorphine -- adverse effects KW - Opioid-Related Disorders -- drug therapy KW - Health Policy -- trends KW - Naloxone -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73261002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Safety+and+health+policy+considerations+related+to+the+use+of+buprenorphine%2Fnaloxone+as+an+office-based+treatment+for+opiate+dependence.&rft.au=Bridge%2C+T+Peter%3BFudala%2C+Paul+J%3BHerbert%2C+Susan%3BLeiderman%2C+Deborah+B&rft.aulast=Bridge&rft.aufirst=T&rft.date=2003-05-21&rft.volume=70&rft.issue=2+Suppl&rft.spage=S79&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=1879-0046&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2009-10-14 N1 - Date created - 2003-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of the combination tablet of buprenorphine and naloxone. AN - 73240522; 12738349 AB - The sublingual combination tablet formulation of buprenorphine and naloxone at a fixed dose ratio of 4:1 has been shown to be as effective as the tablet formulation containing only buprenorphine in treating opiate addiction. The addition of naloxone does not affect the efficacy of buprenorphine for two reasons: (1) naloxone is poorly absorbed sublingually relative to buprenorphine and (2) the half-life for buprenorphine is much longer than for naloxone (32 vs. 1 h for naloxone). The sublingual absorption of buprenorphine is rapid and the peak plasma concentration occurs 1 h after dosing. The plasma levels for naloxone are much lower and decline much more rapidly than those for buprenorphine. Increasing dose results in increasing plasma levels of buprenorphine, although this increase is not directly dose-proportional. There is a large inter-subject variability in plasma buprenorphine levels. Due to the large individual variability in opiate dependence level and the large variability in the pharmacokinetics (PK) of buprenorphine, the effective dose or effective plasma concentration is also quite variable. Doses must be titrated to a clinically effective level for individual patients. JF - Drug and alcohol dependence AU - Chiang, C Nora AU - Hawks, Richard L AD - Division of Treatment Research and Development, National Institute on Drug Abuse, 6001 Executive Blvd, Bethesda, MD 20892, USA. nchiang@nih.gov Y1 - 2003/05/21/ PY - 2003 DA - 2003 May 21 SP - S39 EP - S47 VL - 70 IS - 2 Suppl KW - Buprenorphine, Naloxone Drug Combination KW - 0 KW - Drug Combinations KW - Narcotic Antagonists KW - Tablets KW - Naloxone KW - 36B82AMQ7N KW - Buprenorphine KW - 40D3SCR4GZ KW - Index Medicus KW - Opioid-Related Disorders -- metabolism KW - Humans KW - Opioid-Related Disorders -- drug therapy KW - Administration, Sublingual KW - Narcotic Antagonists -- pharmacokinetics KW - Narcotic Antagonists -- administration & dosage KW - Naloxone -- pharmacokinetics KW - Naloxone -- administration & dosage KW - Buprenorphine -- pharmacokinetics KW - Buprenorphine -- administration & dosage KW - Narcotic Antagonists -- blood KW - Naloxone -- blood KW - Buprenorphine -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73240522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Pharmacokinetics+of+the+combination+tablet+of+buprenorphine+and+naloxone.&rft.au=Chiang%2C+C+Nora%3BHawks%2C+Richard+L&rft.aulast=Chiang&rft.aufirst=C&rft.date=2003-05-21&rft.volume=70&rft.issue=2+Suppl&rft.spage=S39&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=1879-0046&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2009-10-14 N1 - Date created - 2003-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inability to Immunize Patients with Metastatic Melanoma Using Plasmid DNA Encoding the gp100 Melanoma-Melanocyte Antigen AN - 18773600; 5644982 AB - Immunization with plasmid DNA represents a theoretically attractive method for increasing T cell responses against cancer antigens. We administered plasmid DNA encoding the gp100 melanoma-melanocyte differentiation antigen to 22 patients with metastatic melanoma and evaluated immunologic and clinical responses. Patients were randomized to receive plasmid DNA either intradermally (n = 10) or intramuscularly (n = 12). One patient (4.5%) exhibited a partial response of several subcentimeter cutaneous nodules. All other patients had progressive disease. Of 13 patients with cells available before and after immunization, no patient exhibited evidence of the development of anti-gp100 cell responses using in vitro boost assays. The same assays were capable of demonstrating immunologic precursors after immunization with fowl poxvirus encoding gp100 or with gp100 peptides. We were thus unable to demonstrate significant clinical or immunologic responses to plasmid DNA encoding the "self" nonmutated gp100 tumor antigen. JF - Human Gene Therapy AU - Rosenberg, SA AU - Yang, J C AU - Sherry, R M AU - Hwu, P AU - Topalian, S L AU - Schwartzentruber, D J AU - Restifo, N P AU - Haworth, L R AU - Seipp, CA AU - Freezer, L J AU - Morton, KE AU - Mavroukakis, SA AU - White, DE AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B42, 10 Center Drive, MSC 1502, Bethesda, MD 20892-1502, USA, sar@nih.gov Y1 - 2003/05/20/ PY - 2003 DA - 2003 May 20 SP - 709 EP - 714 VL - 14 IS - 8 SN - 1043-0342, 1043-0342 KW - glycoprotein gp100 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - N 14800:Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18773600?accountid=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=Inability+to+Immunize+Patients+with+Metastatic+Melanoma+Using+Plasmid+DNA+Encoding+the+gp100+Melanoma-Melanocyte+Antigen&rft.au=Rosenberg%2C+SA%3BYang%2C+J+C%3BSherry%2C+R+M%3BHwu%2C+P%3BTopalian%2C+S+L%3BSchwartzentruber%2C+D+J%3BRestifo%2C+N+P%3BHaworth%2C+L+R%3BSeipp%2C+CA%3BFreezer%2C+L+J%3BMorton%2C+KE%3BMavroukakis%2C+SA%3BWhite%2C+DE&rft.aulast=Rosenberg&rft.aufirst=SA&rft.date=2003-05-20&rft.volume=14&rft.issue=8&rft.spage=709&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 ER - TY - CPAPER T1 - Mutational analysis of the nuclear orphan receptor CAR AN - 39763029; 3748340 AU - Negishi, M Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39763029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Mutational+analysis+of+the+nuclear+orphan+receptor+CAR&rft.au=Negishi%2C+M&rft.aulast=Negishi&rft.aufirst=M&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Physiological Society, Education Office, 9650 Rockville Pike, Bethesda, MD 20814-3991, USA; phone: (301) 634-7132; fax: (301) 634-7098; email: education@the-aps.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Applications of imaged capillary electrophoresis in biopharmaceutical development AN - 39762555; 3743480 AU - Soman, G Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39762555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Applications+of+imaged+capillary+electrophoresis+in+biopharmaceutical+development&rft.au=Soman%2C+G&rft.aulast=Soman&rft.aufirst=G&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The National Cancer Institute at Frederick, P.O. Box B, Bldg. 549, Frederick, MD 21702-1201, USA; phone: 301-846-1995; fax: 301-846-5866; email: fanningm@ncifcrf.gov; URL: web.ncifcrf.gov N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Application of targeted proteomics for the identification of KSR-binding proteins AN - 39762511; 3743467 AU - Zhou, M AU - Morrison, D AU - Murakami, M AU - Conrads, T P AU - Veenstra, T D Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39762511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Application+of+targeted+proteomics+for+the+identification+of+KSR-binding+proteins&rft.au=Zhou%2C+M%3BMorrison%2C+D%3BMurakami%2C+M%3BConrads%2C+T+P%3BVeenstra%2C+T+D&rft.aulast=Zhou&rft.aufirst=M&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The National Cancer Institute at Frederick, P.O. Box B, Bldg. 549, Frederick, MD 21702-1201, USA; phone: 301-846-1995; fax: 301-846-5866; email: fanningm@ncifcrf.gov; URL: web.ncifcrf.gov N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Structure and mechanism of sulfotransferases AN - 39703725; 3750692 AU - Negishi, M Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39703725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Structure+and+mechanism+of+sulfotransferases&rft.au=Negishi%2C+M&rft.aulast=Negishi&rft.aufirst=M&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Physiological Society, Education Office, 9650 Rockville Pike, Bethesda, MD 20814-3991, USA; phone: (301) 634-7132; fax: (301) 634-7098; email: education@the-aps.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Applications of large volume sample stacking for the analysis of nucleotides in synthetic and biological mixtures by capillary electrophoresis AN - 39702871; 3743481 AU - Lai, C C AU - Kelley, JA Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39702871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Applications+of+large+volume+sample+stacking+for+the+analysis+of+nucleotides+in+synthetic+and+biological+mixtures+by+capillary+electrophoresis&rft.au=Lai%2C+C+C%3BKelley%2C+JA&rft.aulast=Lai&rft.aufirst=C&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The National Cancer Institute at Frederick, P.O. Box B, Bldg. 549, Frederick, MD 21702-1201, USA; phone: 301-846-1995; fax: 301-846-5866; email: fanningm@ncifcrf.gov; URL: web.ncifcrf.gov N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Chemical neuroanatomy of the vesicle monoamine transporters AN - 39644683; 3744136 AU - Eiden, LE Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39644683?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Chemical+neuroanatomy+of+the+vesicle+monoamine+transporters&rft.au=Eiden%2C+LE&rft.aulast=Eiden&rft.aufirst=LE&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Physiological Society, Education Office, 9650 Rockville Pike, Bethesda, MD 20814-3991, USA; phone: (301) 634-7132; fax: (301) 634-7098; email: education@the-aps.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Effect of experimental parameters on the separation of proteins and peptides by micro-HPLC AN - 39635880; 3745293 AU - Fox, S D AU - Mahadevan, M AU - Conrads, T P AU - Veenstra, T D AU - Issaq, HJ Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39635880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Effect+of+experimental+parameters+on+the+separation+of+proteins+and+peptides+by+micro-HPLC&rft.au=Fox%2C+S+D%3BMahadevan%2C+M%3BConrads%2C+T+P%3BVeenstra%2C+T+D%3BIssaq%2C+HJ&rft.aulast=Fox&rft.aufirst=S&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The National Cancer Institute at Frederick, P.O. Box B, Bldg. 549, Frederick, MD 21702-1201, USA; phone: 301-846-1995; fax: 301-846-5866; email: fanningm@ncifcrf.gov; URL: web.ncifcrf.gov N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - IL-2 blockade in transplantation and malignancy AN - 39633944; 3746824 AU - Gea-Banacloche, J C Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39633944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=IL-2+blockade+in+transplantation+and+malignancy&rft.au=Gea-Banacloche%2C+J+C&rft.aulast=Gea-Banacloche&rft.aufirst=J&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Microbiology, 1752 N Street, NW, Washington DC, 20036, USA; phone: 202.737.3600; email: ICAAC@asmusa.org; URL: www.icaac.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Micronutrients and infectious diseases: Integration of mechanistic approaches into micronutrient research AN - 39616013; 3748018 AU - Taylor, CE Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39616013?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Micronutrients+and+infectious+diseases%3A+Integration+of+mechanistic+approaches+into+micronutrient+research&rft.au=Taylor%2C+CE&rft.aulast=Taylor&rft.aufirst=CE&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Microbiology, 1752 N Street, NW, Washington DC, 20036, USA; phone: 202.737.3600; email: ICAAC@asmusa.org; URL: www.icaac.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - In search of susceptibility factors for idiosyncratic drug-induced liver injury AN - 39571915; 3747005 AU - Reilly, T P Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39571915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=In+search+of+susceptibility+factors+for+idiosyncratic+drug-induced+liver+injury&rft.au=Reilly%2C+T+P&rft.aulast=Reilly&rft.aufirst=T&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: International Society for the Study of Xenobiotics, email: jkabiling@issx.org; URL: www.issx.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - IL-12 blockade in inflammatory bowel disease AN - 39562259; 3746821 AU - Strober, W Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39562259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=IL-12+blockade+in+inflammatory+bowel+disease&rft.au=Strober%2C+W&rft.aulast=Strober&rft.aufirst=W&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Microbiology, 1752 N Street, NW, Washington DC, 20036, USA; phone: 202.737.3600; email: ICAAC@asmusa.org; URL: www.icaac.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Sheathless CE-MS interfacing AN - 39552407; 3750379 AU - Janini, G M Y1 - 2003/05/19/ PY - 2003 DA - 2003 May 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39552407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Sheathless+CE-MS+interfacing&rft.au=Janini%2C+G+M&rft.aulast=Janini&rft.aufirst=G&rft.date=2003-05-19&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: The National Cancer Institute at Frederick, P.O. Box B, Bldg. 549, Frederick, MD 21702-1201, USA; phone: 301-846-1995; fax: 301-846-5866; email: fanningm@ncifcrf.gov; URL: web.ncifcrf.gov N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Prenatal methylmercury exposure from ocean fish consumption in the Seychelles child development study. AN - 73326578; 12767734 AB - Exposure to methylmercury (MeHg) before birth can adversely affect children's neurodevelopment. The most common form of prenatal exposure is maternal fish consumption, but whether such exposure harms the fetus is unknown. We aimed to identify adverse neurodevelopmental effects in a fish-consuming population. We investigated 779 mother-infant pairs residing in the Republic of Seychelles. Mothers reported consuming fish on average 12 meals per week. Fish in Seychelles contain much the same concentrations of MeHg as commercial ocean fish elsewhere. Prenatal MeHg exposure was determined from maternal hair growing during pregnancy. We assessed neurocognitive, language, memory, motor, perceptual-motor, and behavioural functions in children at age 9 years. The association between prenatal MeHg exposure and the primary endpoints was investigated with multiple linear regression with adjustment for covariates that affect child development. Mean prenatal MeHg exposure was 6.9 parts per million (SD 4.5 ppm). Only two endpoints were associated with prenatal MeHg exposure. Increased exposure was associated with decreased performance in the grooved pegboard using the non-dominant hand in males and improved scores in the hyperactivity index of the Conner's teacher rating scale. Covariates affecting child development were appropriately associated with endpoints. These data do not support the hypothesis that there is a neurodevelopmental risk from prenatal MeHg exposure resulting solely from ocean fish consumption. JF - Lancet (London, England) AU - Myers, Gary J AU - Davidson, Philip W AU - Cox, Christopher AU - Shamlaye, Conrad F AU - Palumbo, Donna AU - Cernichiari, Elsa AU - Sloane-Reeves, Jean AU - Wilding, Gregory E AU - Kost, James AU - Huang, Li-Shan AU - Clarkson, Thomas W AD - Department of Neurology, National Institute for Child Health and Development, National Institutes of Health, Department of Health and Human Services, Bethesda, USA. gary_myers@urmc.rochester.edu Y1 - 2003/05/17/ PY - 2003 DA - 2003 May 17 SP - 1686 EP - 1692 VL - 361 IS - 9370 SN - 0140-6736, 0140-6736 KW - Methylmercury Compounds KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Regression Analysis KW - Animals KW - Cognition Disorders -- diagnosis KW - Cognition Disorders -- epidemiology KW - Humans KW - Seychelles -- epidemiology KW - Child KW - Cognition Disorders -- chemically induced KW - Comorbidity KW - Pregnancy KW - Infant KW - Fishes KW - Hair -- chemistry KW - Cohort Studies KW - Follow-Up Studies KW - Female KW - Mercury Poisoning -- epidemiology KW - Food Contamination -- analysis KW - Environmental Exposure -- analysis KW - Methylmercury Compounds -- adverse effects KW - Seafood KW - Prenatal Exposure Delayed Effects KW - Methylmercury Compounds -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73326578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Prenatal+methylmercury+exposure+from+ocean+fish+consumption+in+the+Seychelles+child+development+study.&rft.au=Myers%2C+Gary+J%3BDavidson%2C+Philip+W%3BCox%2C+Christopher%3BShamlaye%2C+Conrad+F%3BPalumbo%2C+Donna%3BCernichiari%2C+Elsa%3BSloane-Reeves%2C+Jean%3BWilding%2C+Gregory+E%3BKost%2C+James%3BHuang%2C+Li-Shan%3BClarkson%2C+Thomas+W&rft.aulast=Myers&rft.aufirst=Gary&rft.date=2003-05-17&rft.volume=361&rft.issue=9370&rft.spage=1686&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-18 N1 - Date created - 2003-05-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Lancet. 2003 Aug 23;362(9384):664-5; author reply 665 [12944071] Lancet. 2003 May 17;361(9370):1667-8 [12767728] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific beta1 integrin site selectively regulates Akt/protein kinase B signaling via local activation of protein phosphatase 2A. AN - 73291900; 12637511 AB - Integrin transmembrane receptors generate multiple signals, but how they mediate specific signaling is not clear. Here we test the hypothesis that particular sequences along the beta(1) integrin cytoplasmic domain may exist that are intimately related to specific integrin-mediated signaling pathways. Using systematic alanine mutagenesis of amino acids conserved between different beta integrin cytoplasmic domains, we identified the tryptophan residue at position 775 of human beta(1) integrin as specific and necessary for integrin-mediated protein kinase B/Akt survival signaling. Stable expression of a beta(1) integrin mutated at this amino acid in GD25 beta(1)-null cells resulted in reduction of Akt phosphorylation at both Ser(473) and Thr(308) activation sites. As a consequence, the cells were substantially more sensitive to serum starvation-induced apoptosis when compared with cells expressing wild type beta(1) integrin. This inactivation of Akt resulted from increased dephosphorylation by a localized active population of protein phosphatase 2A. Both Akt and protein phosphatase 2A were present in beta(1) integrin-organized cytoplasmic complexes, but the activity of this phosphatase was 2.5 times higher in the complexes organized by the mutant integrin. The mutation of Trp(775) specifically affected Akt signaling, without effects on other integrin-activated pathways including phosphoinositide 3-kinase, MAPK, JNK, and p38 nor did it influence activation of the integrin-responsive kinases focal adhesion kinase and Src. The identification of Trp(775) as a specific site for integrin-mediated Akt signaling supports the concept of specificity of signaling along the integrin cytoplasmic domain. JF - The Journal of biological chemistry AU - Pankov, Roumen AU - Cukierman, Edna AU - Clark, Katherine AU - Matsumoto, Kazue AU - Hahn, Cornelia AU - Poulin, Benoit AU - Yamada, Kenneth M AD - Craniofacial Developmental Biology and Regeneration Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892-4370, USA. roumen.pankov@nih.gov Y1 - 2003/05/16/ PY - 2003 DA - 2003 May 16 SP - 18671 EP - 18681 VL - 278 IS - 20 SN - 0021-9258, 0021-9258 KW - Antigens, CD29 KW - 0 KW - DNA, Complementary KW - Integrins KW - Proto-Oncogene Proteins KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Akt1 protein, rat KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Protein Phosphatase 2 KW - Index Medicus KW - Animals KW - Apoptosis KW - Humans KW - Microscopy, Fluorescence KW - Rats KW - Phosphorylation KW - Cytoplasm -- metabolism KW - Molecular Sequence Data KW - Flow Cytometry KW - Time Factors KW - Signal Transduction KW - Immunoblotting KW - Mitogen-Activated Protein Kinases -- metabolism KW - Amino Acid Sequence KW - Mice KW - Precipitin Tests KW - Protein Binding KW - Binding Sites KW - Base Sequence KW - Transfection KW - DNA, Complementary -- metabolism KW - Integrins -- metabolism KW - Protein Structure, Tertiary KW - Mutation KW - Cell Line KW - Antigens, CD29 -- metabolism KW - Antigens, CD29 -- chemistry KW - Proto-Oncogene Proteins -- metabolism KW - Phosphoprotein Phosphatases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73291900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+beta1+integrin+site+selectively+regulates+Akt%2Fprotein+kinase+B+signaling+via+local+activation+of+protein+phosphatase+2A.&rft.au=Pankov%2C+Roumen%3BCukierman%2C+Edna%3BClark%2C+Katherine%3BMatsumoto%2C+Kazue%3BHahn%2C+Cornelia%3BPoulin%2C+Benoit%3BYamada%2C+Kenneth+M&rft.aulast=Pankov&rft.aufirst=Roumen&rft.date=2003-05-16&rft.volume=278&rft.issue=20&rft.spage=18671&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 - 2003-06-25 N1 - Date created - 2003-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I study of a lipooligosaccharide-based conjugate vaccine against nontypeable Haemophilus influenzae. AN - 73207382; 12706701 AB - Nontypeable Haemophilus influenzae (NTHi) accounts for about one-third of purulent otitis media (OM) in children and is a common cause of pulmonary infection in adults with decreased resistance. Based upon sero-epidemiological data in humans and immunochemical data in laboratory animals, a lipooligosaccharide (LOS)-tetanus toxoid (TT) conjugate was prepared and evaluated for its safety and immunogenicity in a Phase I study of 40 healthy adults. The conjugate was injected intramuscularly into all volunteers: 28 of them received a second injection 14 weeks later. Local and systemic reactions were monitored and sera, taken before and 2, 6, 14, 16, and 38 weeks after injection, were assayed for IgG, IgA, and IgM antibodies to the LOS by ELISA and for bactericidal activity. The results indicate that there were no significant local or systemic reactions after either injection. All volunteers had pre-existing IgG anti-LOS. The geometric mean (GM) level rose from 14 to 40 at 2 weeks, remained at 35 at 6 weeks (40 or 35 versus 14, P<0.01) and dropped to 27 at 14 weeks after the first injection. There was also a rise 2 weeks after the second injection (27 versus 37, P<0.05). A total of 52.5% of subjects showed serum-conversion (greater than four-fold increase) after one and two injections. At 38 weeks, the GM IgG anti-LOS was still higher than before initial injection (20 versus 14, P<0.05). A similar pattern of reactivity was observed for IgA and IgM anti-LOS. Similar to that observed in mice, but not in rabbits, the conjugate-induced antibodies did not yield significant bactericidal activity in vitro. The LOS-TT conjugate is well tolerant in adults and a Phase II evaluation of the conjugate in children is planned. JF - Vaccine AU - Gu, Xin-Xing AU - Rudy, Susan F AU - Chu, Chiayung AU - McCullagh, Linda AU - Kim, Hung N AU - Chen, Jing AU - Li, Jianping AU - Robbins, John B AU - Van Waes, Carter AU - Battey, James F AD - National Institute on Deafness and Other Communication Disorders, 5 Research Court, Rockville, MD 20850, USA. guxx@nidcd.nih.gov Y1 - 2003/05/16/ PY - 2003 DA - 2003 May 16 SP - 2107 EP - 2114 VL - 21 IS - 17-18 SN - 0264-410X, 0264-410X KW - Antibodies, Bacterial KW - 0 KW - Haemophilus Vaccines KW - Immunoglobulin A KW - Immunoglobulin G KW - Immunoglobulin M KW - Lipopolysaccharides KW - Tetanus Toxoid KW - Vaccines, Conjugate KW - lipid-linked oligosaccharides KW - Index Medicus KW - Animals KW - Reference Values KW - Otitis Media -- immunology KW - Humans KW - Antibody Formation KW - Child KW - Mice KW - Immunoglobulin G -- blood KW - Immunoglobulin M -- blood KW - Adult KW - Antibodies, Bacterial -- blood KW - Enzyme-Linked Immunosorbent Assay KW - Otitis Media -- microbiology KW - Immunoglobulin A -- blood KW - Time Factors KW - Tetanus Toxoid -- immunology KW - Haemophilus Infections -- immunology KW - Vaccines, Conjugate -- toxicity KW - Lipopolysaccharides -- immunology KW - Haemophilus influenzae -- classification KW - Haemophilus Vaccines -- toxicity KW - Haemophilus influenzae -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73207382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Phase+I+study+of+a+lipooligosaccharide-based+conjugate+vaccine+against+nontypeable+Haemophilus+influenzae.&rft.au=Gu%2C+Xin-Xing%3BRudy%2C+Susan+F%3BChu%2C+Chiayung%3BMcCullagh%2C+Linda%3BKim%2C+Hung+N%3BChen%2C+Jing%3BLi%2C+Jianping%3BRobbins%2C+John+B%3BVan+Waes%2C+Carter%3BBattey%2C+James+F&rft.aulast=Gu&rft.aufirst=Xin-Xing&rft.date=2003-05-16&rft.volume=21&rft.issue=17-18&rft.spage=2107&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-21 N1 - Date created - 2003-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HutC/FarR-like bacterial transcription factors of the GntR family contain a small molecule-binding domain of the chorismate lyase fold AN - 18786788; 5657629 AB - Numerous bacterial transcription factors contain a DNA-binding helix-turn-helix domain and a signaling domain, linked together in a single polypeptide. Typically, this signaling domain is a small-molecule-binding domain that undergoes a conformational change upon recognizing a specific ligand. The HutC/FarR-like transcription factors of the GntR family are one of the largest groups of transcription factors in the proteomes of most free-living bacteria. Using sensitive sequence profile analysis we show that the HutC/FarR-like transcription factors contain a conserved ligand-binding domain, which possesses the same fold as chorismate lyase (Escherichia coli UbiC gene product). This relationship suggests that the C-terminal domain of the HutC /FarR-like transcription factors binds small molecules in a cleft similar to the substrate-binding site of the chorismate lyases. The sequence diversity within the predicted binding cleft of the HutC /FarR ligand-binding domains is consistent with the ability of these transcription factors to respond to diverse small molecules, such as histidine (HutC), fatty acids (FarR), sugars (TreR) and alkylphosphonate (PhnF). UbiC-like chorismate lyases function in the ubiquinone biosynthesis pathway, and have characteristic charged, catalytic residues. Genome comparisons reveal that chorismate lyase orthologs are found in several bacteria, chloroplasts of eukaryotic algae and euryarchaea. In contrast, the GntR transcription regulators lack the conserved catalytic residues of the chorismate lyases, and have so far been detected only in bacteria. An ancestral, generic small-molecule-binding domain appears to have given rise to the enzymatic and non-catalytic ligand-binding versions of the same fold under the influence of different selective pressures. JF - FEMS Microbiology Letters AU - Aravind, L AU - Anantharaman, 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 - 2003/05/16/ PY - 2003 DA - 2003 May 16 SP - 17 EP - 23 PB - Federation of European Microbiological Societies VL - 222 IS - 1 SN - 0378-1097, 0378-1097 KW - FarR protein KW - GntR protein KW - HutC protein KW - chorismate lyase KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02726:RNA and ribosomes KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18786788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=HutC%2FFarR-like+bacterial+transcription+factors+of+the+GntR+family+contain+a+small+molecule-binding+domain+of+the+chorismate+lyase+fold&rft.au=Aravind%2C+L%3BAnantharaman%2C+V&rft.aulast=Aravind&rft.aufirst=L&rft.date=2003-05-16&rft.volume=222&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/10.1016%2FS0378-1097%2803%2900242-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0378-1097(03)00242-8 ER - TY - JOUR T1 - A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. AN - 73305197; 12746765 AB - A randomized, blinded, multicenter trial was conducted to compare fluconazole (800 mg per day) plus placebo with fluconazole plus amphotericin B (AmB) deoxycholate (0.7 mg/kg per day, with the placebo/AmB component given only for the first 5-6 days) as therapy for candidemia due to species other than Candida krusei in adults without neutropenia. A total of 219 patients met criteria for a modified intent-to-treat analysis. The groups were similar except that those who were treated with fluconazole plus placebo had a higher mean (+/- standard error) Acute Physiology and Chronic Health Evaluation II score (16.8+/-0.6 vs. 15.0+/-0.7; P=.039). Success rates on study day 30 by Kaplan-Meier time-to-failure analysis were 57% for fluconazole plus placebo and 69% for fluconazole plus AmB (P=.08). Overall success rates were 56% (60 of 107 patients) and 69% (77 of 112 patients; P=.043), respectively; the bloodstream infection failed to clear in 17% and 6% of subjects, respectively (P=.02). In nonneutropenic subjects, the combination of fluconazole plus AmB was not antagonistic compared with fluconazole alone, and the combination trended toward improved success and more-rapid clearance from the bloodstream. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Rex, John H AU - Pappas, Peter G AU - Karchmer, Adolf W AU - Sobel, Jack AU - Edwards, John E AU - Hadley, Susan AU - Brass, Corstiaan AU - Vazquez, Jose A AU - Chapman, Stanley W AU - Horowitz, Harold W AU - Zervos, Marcus AU - McKinsey, David AU - Lee, Jeannette AU - Babinchak, Timothy AU - Bradsher, Robert W AU - Cleary, John D AU - Cohen, David M AU - Danziger, Larry AU - Goldman, Mitchell AU - Goodman, Jesse AU - Hilton, Eileen AU - Hyslop, Newton E AU - Kett, Daniel H AU - Lutz, Jon AU - Rubin, Robert H AU - Scheld, W Michael AU - Schuster, Mindy AU - Simmons, Bryan AU - Stein, David K AU - Washburn, Ronald G AU - Mautner, Linda AU - Chu, Teng-Chiao AU - Panzer, Helene AU - Rosenstein, Rebecca B AU - Booth, Jenia AU - National Institute of Allergy and Infectious Diseases Mycoses Study Group AD - Division of Infectious Diseases, University of Texas Medical School, Houston, TX 77030, USA. john@rexweb.org ; National Institute of Allergy and Infectious Diseases Mycoses Study Group Y1 - 2003/05/15/ PY - 2003 DA - 2003 May 15 SP - 1221 EP - 1228 VL - 36 IS - 10 KW - Antifungal Agents KW - 0 KW - Amphotericin B KW - 7XU7A7DROE KW - Fluconazole KW - 8VZV102JFY KW - Index Medicus KW - Drug Therapy, Combination KW - Catheterization KW - Candida -- drug effects KW - Double-Blind Method KW - Neutropenia -- etiology KW - Humans KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Male KW - Female KW - Fluconazole -- adverse effects KW - Candidiasis -- drug therapy KW - Candidiasis -- physiopathology KW - Antifungal Agents -- adverse effects KW - Fluconazole -- therapeutic use KW - Fungemia -- drug therapy KW - Amphotericin B -- adverse effects KW - Amphotericin B -- therapeutic use KW - Fungemia -- physiopathology KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73305197?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=A+randomized+and+blinded+multicenter+trial+of+high-dose+fluconazole+plus+placebo+versus+fluconazole+plus+amphotericin+B+as+therapy+for+candidemia+and+its+consequences+in+nonneutropenic+subjects.&rft.au=Rex%2C+John+H%3BPappas%2C+Peter+G%3BKarchmer%2C+Adolf+W%3BSobel%2C+Jack%3BEdwards%2C+John+E%3BHadley%2C+Susan%3BBrass%2C+Corstiaan%3BVazquez%2C+Jose+A%3BChapman%2C+Stanley+W%3BHorowitz%2C+Harold+W%3BZervos%2C+Marcus%3BMcKinsey%2C+David%3BLee%2C+Jeannette%3BBabinchak%2C+Timothy%3BBradsher%2C+Robert+W%3BCleary%2C+John+D%3BCohen%2C+David+M%3BDanziger%2C+Larry%3BGoldman%2C+Mitchell%3BGoodman%2C+Jesse%3BHilton%2C+Eileen%3BHyslop%2C+Newton+E%3BKett%2C+Daniel+H%3BLutz%2C+Jon%3BRubin%2C+Robert+H%3BScheld%2C+W+Michael%3BSchuster%2C+Mindy%3BSimmons%2C+Bryan%3BStein%2C+David+K%3BWashburn%2C+Ronald+G%3BMautner%2C+Linda%3BChu%2C+Teng-Chiao%3BPanzer%2C+Helene%3BRosenstein%2C+Rebecca+B%3BBooth%2C+Jenia%3BNational+Institute+of+Allergy+and+Infectious+Diseases+Mycoses+Study+Group&rft.aulast=Rex&rft.aufirst=John&rft.date=2003-05-15&rft.volume=36&rft.issue=10&rft.spage=1221&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-10 N1 - Date created - 2003-05-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Infect Dis. 2003 May 15;36(10):1229-31 [12746766] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Triad of acute infusion-related reactions associated with liposomal amphotericin B: analysis of clinical and epidemiological characteristics. AN - 73302681; 12746764 AB - We investigated the clinical characteristics and treatment of patients with a distinctive triad of acute infusion-related reactions (AIRRs) to liposomal amphotericin B (L-AMB) via single-center and multicenter analyses. AIRRs occurred alone or in combination within 1 of 3 symptom complexes: (1) chest pain, dyspnea, and hypoxia; (2) severe abdomen, flank, or leg pain; and (3) flushing and urticaria. The frequency of AIRRs in the single-center analysis increased over time. Most AIRRs (86%) occurred within the first 5 min of infusion. All patients experienced rapid resolution of symptoms after intravenous diphenhydramine was administered. The multicenter analysis demonstrated a mean overall frequency of 20% (range, 0%-100%) of AIRRs among 64 centers. A triad of severe AIRRs to L-AMB may occur in some centers; most of these reactions may be effectively managed by diphenhydramine administration and interruption of L-AMB infusion. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Roden, Maureen M AU - Nelson, Lucienne D AU - Knudsen, Tena A AU - Jarosinski, Paul F AU - Starling, Judith M AU - Shiflett, Stacey E AU - Calis, Karim AU - DeChristoforo, Robert AU - Donowitz, Gerald R AU - Buell, Donald AU - Walsh, Thomas J AD - Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health Clinical Center, Bethesda, Maryland 20892, USA. Y1 - 2003/05/15/ PY - 2003 DA - 2003 May 15 SP - 1213 EP - 1220 VL - 36 IS - 10 KW - Antifungal Agents KW - 0 KW - Drug Combinations KW - Liposomes KW - Phosphatidylcholines KW - Phosphatidylglycerols KW - liposomal amphotericin B KW - Amphotericin B KW - 7XU7A7DROE KW - Index Medicus KW - Abdominal Pain -- etiology KW - Humans KW - Phosphatidylglycerols -- adverse effects KW - Phosphatidylcholines -- adverse effects KW - Chest Pain -- etiology KW - Flushing -- etiology KW - Risk Factors KW - Adult KW - Hypoxia -- etiology KW - Dyspnea -- etiology KW - Female KW - Male KW - Antifungal Agents -- adverse effects KW - Amphotericin B -- adverse effects KW - Amphotericin B -- administration & dosage KW - Antifungal Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73302681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Triad+of+acute+infusion-related+reactions+associated+with+liposomal+amphotericin+B%3A+analysis+of+clinical+and+epidemiological+characteristics.&rft.au=Roden%2C+Maureen+M%3BNelson%2C+Lucienne+D%3BKnudsen%2C+Tena+A%3BJarosinski%2C+Paul+F%3BStarling%2C+Judith+M%3BShiflett%2C+Stacey+E%3BCalis%2C+Karim%3BDeChristoforo%2C+Robert%3BDonowitz%2C+Gerald+R%3BBuell%2C+Donald%3BWalsh%2C+Thomas+J&rft.aulast=Roden&rft.aufirst=Maureen&rft.date=2003-05-15&rft.volume=36&rft.issue=10&rft.spage=1213&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-10 N1 - Date created - 2003-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. AN - 73277068; 12750254 AB - We identified and characterized two new ING family genes, p29ING4 and p28ING5,coding for two proteins of 249 and 240 amino acids, respectively. Both p29ING4 and p28ING5 proteins have a plant homeodomain finger motif also found in other ING proteins, and which is common in proteins involved in chromatin remodeling. p29ING4 or p28ING5 overexpression resulted in a diminished colony-forming efficiency, a decreased cell population in S phase, and the induction of apoptosis in a p53-dependent manner. Both p29ING4 and p28ING5 activate the p21/waf1 promoter, and induce p21/WAF1 expression. p29ING4 and p28ING5 enhance p53 acetylation at Lys-382 residues, and physically interact with p300, a member of histone acetyl transferase complexes, and p53 in vivo. These results indicate that p29ING4 and p28ING5 may be significant modulators of p53 function. JF - Cancer research AU - Shiseki, Masayuki AU - Nagashima, Makoto AU - Pedeux, Remy M AU - Kitahama-Shiseki, Mariko AU - Miura, Koh AU - Okamura, Shu AU - Onogi, Hitoshi AU - Higashimoto, Yuichiro AU - Appella, Ettore AU - Yokota, Jun AU - Harris, Curtis C AD - Laboratories of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2003/05/15/ PY - 2003 DA - 2003 May 15 SP - 2373 EP - 2378 VL - 63 IS - 10 SN - 0008-5472, 0008-5472 KW - Cell Cycle Proteins KW - 0 KW - DNA, Complementary KW - Growth Inhibitors KW - Homeodomain Proteins KW - ING4 protein, human KW - ING5 protein, human KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - Tumor Suppressor Proteins KW - Acetyltransferases KW - EC 2.3.1.- KW - Histone Acetyltransferases KW - EC 2.3.1.48 KW - p300-CBP Transcription Factors KW - p300-CBP-associated factor KW - Index Medicus KW - DNA, Complementary -- genetics KW - Colorectal Neoplasms -- metabolism KW - Humans KW - Cell Division -- physiology KW - Amino Acid Sequence KW - Colorectal Neoplasms -- genetics KW - Protein Binding KW - Cloning, Molecular KW - Acetylation KW - Tumor Cells, Cultured KW - Transfection KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Homeodomain Proteins -- genetics KW - Acetyltransferases -- metabolism KW - Growth Inhibitors -- genetics KW - Tumor Suppressor Proteins -- metabolism KW - Tumor Suppressor Proteins -- genetics KW - Homeodomain Proteins -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Growth Inhibitors -- metabolism KW - Cell Cycle Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73277068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p29ING4+and+p28ING5+bind+to+p53+and+p300%2C+and+enhance+p53+activity.&rft.au=Shiseki%2C+Masayuki%3BNagashima%2C+Makoto%3BPedeux%2C+Remy+M%3BKitahama-Shiseki%2C+Mariko%3BMiura%2C+Koh%3BOkamura%2C+Shu%3BOnogi%2C+Hitoshi%3BHigashimoto%2C+Yuichiro%3BAppella%2C+Ettore%3BYokota%2C+Jun%3BHarris%2C+Curtis+C&rft.aulast=Shiseki&rft.aufirst=Masayuki&rft.date=2003-05-15&rft.volume=63&rft.issue=10&rft.spage=2373&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 - 2003-06-23 N1 - Date created - 2003-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 interacts with hRAD51 and hRAD54, and directly modulates homologous recombination. AN - 73268815; 12750285 AB - p53 inhibits tumorigenesis through a variety of functions, including mediation of cell cycle arrest, premature senescence, and apoptosis.p53 also can associate with several DNA helicases and proteins involved in homologous recombination. In this study, we show that p53, hRAD51, and hRAD54 coimmunoprecipitated and colocalized with each other at endogenous levels in normal cells. Colocalization was observed with the phosphoserine-15 form of p53 at presumed DNA processing sites after the induction of DNA breaks. hRAD54 bound directly to the p53 COOH terminus in vitro without a nucleic acid intermediate. We then investigated the functional consequences of these protein interactions. A host cell reactivation assay revealed that the elevation in recombination observed after p53 inactivation is dependent on the hRAD51 pathway and that p53-dependent antirecombinogenic activity can be attributed to p53 binding to hRAD51 directly. These data support the hypothesis that p53 helps maintain genetic stability through transcription-independent modulation of homologous recombination factors. JF - Cancer research AU - Linke, Steven P AU - Sengupta, Sagar AU - Khabie, Nissim AU - Jeffries, Beth A AU - Buchhop, Sabine AU - Miska, Stefan AU - Henning, Wilhelm AU - Pedeux, Remy AU - Wang, Xin W AU - Hofseth, Lorne J AU - Yang, Qin AU - Garfield, Susan H AU - Stürzbecher, Horst-Werner AU - Harris, Curtis C AD - Laboratories of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 2003/05/15/ PY - 2003 DA - 2003 May 15 SP - 2596 EP - 2605 VL - 63 IS - 10 SN - 0008-5472, 0008-5472 KW - DNA-Binding Proteins KW - 0 KW - Nuclear Proteins KW - RAD54L protein, human KW - Tumor Suppressor Protein p53 KW - RAD51 protein, human KW - EC 2.7.7.- KW - Rad51 Recombinase KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Cell Nucleus -- metabolism KW - Humans KW - Protein Structure, Tertiary KW - Protein Binding KW - Cell Line KW - Fibroblasts KW - Tumor Suppressor Protein p53 -- physiology KW - DNA-Binding Proteins -- physiology KW - DNA-Binding Proteins -- antagonists & inhibitors KW - Recombination, Genetic -- physiology KW - Nuclear Proteins -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Nuclear Proteins -- physiology KW - Tumor Suppressor Protein p53 -- deficiency KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73268815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=p53+interacts+with+hRAD51+and+hRAD54%2C+and+directly+modulates+homologous+recombination.&rft.au=Linke%2C+Steven+P%3BSengupta%2C+Sagar%3BKhabie%2C+Nissim%3BJeffries%2C+Beth+A%3BBuchhop%2C+Sabine%3BMiska%2C+Stefan%3BHenning%2C+Wilhelm%3BPedeux%2C+Remy%3BWang%2C+Xin+W%3BHofseth%2C+Lorne+J%3BYang%2C+Qin%3BGarfield%2C+Susan+H%3BSt%C3%BCrzbecher%2C+Horst-Werner%3BHarris%2C+Curtis+C&rft.aulast=Linke&rft.aufirst=Steven&rft.date=2003-05-15&rft.volume=63&rft.issue=10&rft.spage=2596&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 - 2003-06-23 N1 - Date created - 2003-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidant-induced cell death in retinal pigment epithelium cells mediated through the release of apoptosis-inducing factor. AN - 73192778; 12668724 AB - In the present study, the pathways involved in oxidant-induced cell death of a primary cell of the retina, ARPE-19, were investigated and compared with a leukemic cell, U937 cells. Both ARPE-19 and U937 cells exhibited similar viability when exposed to menadione. At lethal doses, both cell lines demonstrated extensive membrane blebbing. However, although U937 cells exhibited caspase-3, -9 PARP cleavage and 200 bp laddering, no such cleavage or laddering was noted in ARPE-19 cells. Furthermore, addition of exogenous cytochrome c and ATP to a cell-free system again resulted in cleavage of caspase-3 and -9 in extracts of U937 but not ARPE cells. Further studies in ARPE-19 cells undergoing menadione-induced cell death demonstrated mitochondrial membrane depolarization, release of cytochrome c, nuclear translocation of apoptosis-inducing factor and subsequent 50 kilo-base pair laddering, and nuclear shrinkage. All of these findings were abrogated by the pretreatment of ARPE-19 cells with hepatocyte growth factor/scatter factor. These findings demonstrate the complex nature of cell death in primary cells of the retina and highlight the role of caspase-independent signals, growth factors and intracellular survival factors in programmed cell death pathways. JF - Journal of cell science AU - Zhang, Congxiao AU - Baffi, Judit AU - Cousins, Scott W AU - Csaky, Karl G AD - National Eye Institute, Building 10 - Room 10N119, 9000 Rockville Pike, Bethesda, Maryland 20892-1857, USA. Y1 - 2003/05/15/ PY - 2003 DA - 2003 May 15 SP - 1915 EP - 1923 VL - 116 SN - 0021-9533, 0021-9533 KW - AIFM1 protein, human KW - 0 KW - Apoptosis Inducing Factor KW - Flavoproteins KW - Membrane Proteins KW - Oxidants KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Cytochromes c KW - 9007-43-6 KW - DNA KW - 9007-49-2 KW - Caspases KW - EC 3.4.22.- KW - Index Medicus KW - Cytochromes c -- metabolism KW - Apoptosis KW - Cell Nucleus -- metabolism KW - Humans KW - Caspases -- metabolism KW - Cell Survival KW - Microscopy, Fluorescence KW - Retina -- cytology KW - DNA Fragmentation KW - Cell-Free System -- metabolism KW - Dose-Response Relationship, Drug KW - Enzyme Activation KW - DNA -- metabolism KW - Hepatocyte Growth Factor -- metabolism KW - Blotting, Western KW - Cell Death KW - Adenosine Triphosphate -- metabolism KW - Mitochondria -- metabolism KW - Cell Membrane -- metabolism KW - Subcellular Fractions -- metabolism KW - Immunohistochemistry KW - Cell Line KW - U937 Cells KW - Protein Transport KW - Flavoproteins -- metabolism KW - Membrane Proteins -- metabolism KW - Pigment Epithelium of Eye -- cytology KW - Oxidants -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73192778?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell+science&rft.atitle=Oxidant-induced+cell+death+in+retinal+pigment+epithelium+cells+mediated+through+the+release+of+apoptosis-inducing+factor.&rft.au=Zhang%2C+Congxiao%3BBaffi%2C+Judit%3BCousins%2C+Scott+W%3BCsaky%2C+Karl+G&rft.aulast=Zhang&rft.aufirst=Congxiao&rft.date=2003-05-15&rft.volume=116&rft.issue=&rft.spage=1915&rft.isbn=&rft.btitle=&rft.title=Journal+of+cell+science&rft.issn=00219533&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-22 N1 - Date created - 2003-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypermethylation of GSTP1, CD44, and E-cadherin genes in prostate cancer among US Blacks and Whites. AN - 73189673; 12692786 AB - In the US, the incidence and mortality of prostate cancer is about twofold higher among US Blacks compared to Whites, suggesting racial differences in prostate tumor occurrence and aggressiveness. The reason for these racial differences is unknown. Epigenetic events such as promoter-region gene hypermethylation may be influenced by environmental exposures and have been implicated in prostate carcinogenesis (by the silencing of tumor suppressors and other regulatory genes). Using real-time methylation-sensitive PCR, we assessed differences in DNA hypermethylation of GSTP1, CD44, and E-cadherin (three genes thought to be important in the progression of prostate cancer) in archival tumor tissue of black (n = 47) and white men (n = 64). We found a high prevalence of GSTP1 hypermethylation overall (84%) but no differences by race (89 and 83% in black vs. white men, respectively), tumor stage, or grade. Although CD44 hypermethylation was less prevalent overall (found in 32% of tumors), we observed a 1.7-fold higher frequency among black men (43 vs. 25% in black vs. white men, P = 0.05) and a correlation with tumor grade (CD44 was hypermethylated in 10, 42, and 52% of well, moderate, and poorly differentiated tumors, respectively, P = 0.003) but not disease stage. The E-cadherin gene was not hypermethylated in any of the tumors. In summary, of the three genes examined, only CD44 hypermethylation differed by race and correlated with tumor grade, independent of race. These preliminary findings suggest that differences in gene promoter hypermethylation may potentially underlie racial differences in prostate cancer pathogenesis and should be explored in larger studies. Copyright 2003 Wiley-Liss, Inc. JF - The Prostate AU - Woodson, Karen AU - Hayes, Richard AU - Wideroff, Louise AU - Villaruz, Liza AU - Tangrea, Joseph AD - Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. kw114@nih.gov Y1 - 2003/05/15/ PY - 2003 DA - 2003 May 15 SP - 199 EP - 205 VL - 55 IS - 3 SN - 0270-4137, 0270-4137 KW - Antigens, CD44 KW - 0 KW - Cadherins KW - DNA, Neoplasm KW - Isoenzymes KW - GSTP1 protein, human KW - EC 2.5.1.18 KW - Glutathione S-Transferase pi KW - Glutathione Transferase KW - Index Medicus KW - Humans KW - European Continental Ancestry Group KW - Polymerase Chain Reaction -- methods KW - DNA, Neoplasm -- genetics KW - Aged KW - Middle Aged KW - DNA, Neoplasm -- metabolism KW - African Continental Ancestry Group KW - Male KW - Cadherins -- metabolism KW - DNA Methylation KW - Antigens, CD44 -- genetics KW - Glutathione Transferase -- metabolism KW - Prostatic Neoplasms -- genetics KW - Glutathione Transferase -- genetics KW - Isoenzymes -- genetics KW - Cadherins -- genetics KW - Antigens, CD44 -- metabolism KW - Isoenzymes -- metabolism KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73189673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Prostate&rft.atitle=Hypermethylation+of+GSTP1%2C+CD44%2C+and+E-cadherin+genes+in+prostate+cancer+among+US+Blacks+and+Whites.&rft.au=Woodson%2C+Karen%3BHayes%2C+Richard%3BWideroff%2C+Louise%3BVillaruz%2C+Liza%3BTangrea%2C+Joseph&rft.aulast=Woodson&rft.aufirst=Karen&rft.date=2003-05-15&rft.volume=55&rft.issue=3&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=The+Prostate&rft.issn=02704137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-23 N1 - Date created - 2003-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol Concentration and Risk of Oral Cancer in Puerto Rico AN - 19221484; 5797062 AB - Alcohol consumption is a major risk factor for cancers of the mouth and pharynx (oral cancer), but the differential risks by beverage type are unclear. In this 1992-1995 study, the authors examined oral cancer risk in Puerto Rico, comparing alcohol intake among 286 male cases aged 21-79 years and 417 population-based male controls, frequency matched by age. Heavy consumers of liquor ( greater than or equal to 43 drinks per week) had strongly increased risks of oral cancer (odds ratio = 6.4, 95% confidence interval: 2.4, 16.8); beer/wine showed only modest effects. Among liquor drinkers, risks were consistently greater for those who drank straight (undiluted) liquor than for those who usually drank mixed (diluted) liquor (odds ratio = 4.0, 95% confidence interval: 2.4, 6.7). Risks associated with combined exposure to tobacco were also more pronounced when subjects drank liquor straight. The elevated risks associated with drinking homemade rum were similar to those for other types of liquor. These results suggest that alcohol concentration is a risk factor for oral cancer independent of the total quantity of alcohol consumed. JF - American Journal of Epidemiology AU - Huang, W-Y AU - Winn, D M AU - Brown, L M AU - Gridley, G AU - Bravo-Otero, E AU - Diehl AU - Fraumeni, JF Jr AU - Hayes, R B AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA Y1 - 2003/05/15/ PY - 2003 DA - 2003 May 15 SP - 881 EP - 887 VL - 157 IS - 10 SN - 0002-9262, 0002-9262 KW - oral cavity KW - Health & Safety Science Abstracts KW - Risk assessment KW - Alcohol KW - Puerto Rico KW - Cancer KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19221484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Alcohol+Concentration+and+Risk+of+Oral+Cancer+in+Puerto+Rico&rft.au=Huang%2C+W-Y%3BWinn%2C+D+M%3BBrown%2C+L+M%3BGridley%2C+G%3BBravo-Otero%2C+E%3BDiehl%3BFraumeni%2C+JF+Jr%3BHayes%2C+R+B&rft.aulast=Huang&rft.aufirst=W-Y&rft.date=2003-05-15&rft.volume=157&rft.issue=10&rft.spage=881&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Puerto Rico; Cancer; Alcohol; Risk assessment ER - TY - JOUR T1 - Anthrax lethal factor represses glucocorticoid and progesterone receptor activity. AN - 73314259; 12724519 AB - We report here that a bacterial toxin, anthrax lethal toxin (LeTx), at very low concentrations represses glucocorticoid receptor (GR) transactivation in a transient transfection system and the activity of an endogenous GR-regulated gene in both a cellular system and an animal model. This repression is noncompetitive and does not affect ligand binding or DNA binding, suggesting that anthrax lethal toxin (LeTx) probably exerts its effects through a cofactor(s) involved in the interaction between GR and the basal transcription machinery. LeTx-nuclear receptor repression is selective, repressing GR, progesterone receptor B (PR-B), and estrogen receptor alpha (ERalpha), but not the mineralocorticoid receptor (MR) or ERbeta. GR repression was also caused by selected p38 mitogen-activated protein (MAP) kinase inhibitors, suggesting that the LeTx action may result in part from its known inactivation of MAP kinases. Simultaneous loss of GR and other nuclear receptor activities could render an animal more susceptible to lethal or toxic effects of anthrax infection by removing the normally protective antiinflammatory effects of these hormones, similar to the increased mortality seen in animals exposed to both GR antagonists and infectious agents or bacterial products. These finding have implications for development of new treatments and prevention of the toxic effects of anthrax. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Webster, Jeanette I AU - Tonelli, Leonardo H AU - Moayeri, Mahtab AU - Simons, S Stoney AU - Leppla, Stephen H AU - Sternberg, Esther M AD - Section on Neuroendocrine Immunology and Behavior, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/05/13/ PY - 2003 DA - 2003 May 13 SP - 5706 EP - 5711 VL - 100 IS - 10 SN - 0027-8424, 0027-8424 KW - 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one KW - 0 KW - Antigens, Bacterial KW - Bacterial Toxins KW - Enzyme Inhibitors KW - Flavonoids KW - Receptors, Glucocorticoid KW - Receptors, Progesterone KW - Recombinant Proteins KW - anthrax toxin KW - Mifepristone KW - 320T6RNW1F KW - Dexamethasone KW - 7S5I7G3JQL KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Index Medicus KW - Animals KW - COS Cells KW - Dexamethasone -- pharmacology KW - Mice KW - Mice, Inbred BALB C KW - Bacillus anthracis KW - Mifepristone -- pharmacology KW - Transfection KW - Kinetics KW - Cercopithecus aethiops KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Flavonoids -- pharmacology KW - Recombinant Proteins -- antagonists & inhibitors KW - Female KW - Male KW - Receptors, Glucocorticoid -- antagonists & inhibitors KW - Bacterial Toxins -- pharmacology KW - Receptors, Progesterone -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73314259?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Anthrax+lethal+factor+represses+glucocorticoid+and+progesterone+receptor+activity.&rft.au=Webster%2C+Jeanette+I%3BTonelli%2C+Leonardo+H%3BMoayeri%2C+Mahtab%3BSimons%2C+S+Stoney%3BLeppla%2C+Stephen+H%3BSternberg%2C+Esther+M&rft.aulast=Webster&rft.aufirst=Jeanette&rft.date=2003-05-13&rft.volume=100&rft.issue=10&rft.spage=5706&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 - 2003-07-01 N1 - Date created - 2003-05-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: FEBS Lett. 1999 Nov 26;462(1-2):199-204 [10580119] J Bacteriol. 1963 May;85:1032-8 [14043991] Cell Biol Toxicol. 2000;16(2):137-44 [10917569] Biochem J. 2000 Dec 15;352 Pt 3:739-45 [11104681] Int J Med Microbiol. 2000 Oct;290(4-5):421-7 [11111921] Infect Immun. 2001 Feb;69(2):1175-7 [11160016] J Endocrinol. 2001 Jun;169(3):447-51 [11375114] Oncogene. 2001 Apr 30;20(19):2465-75 [11402341] J Biol Chem. 2001 Jun 22;276(25):22177-82 [11301320] Curr Biol. 2001 Oct 2;11(19):1503-11 [11591317] Crit Rev Microbiol. 2001;27(3):167-200 [11596878] Nature. 2001 Nov 8;414(6860):225-9 [11700562] Curr Microbiol. 2002 Feb;44(2):106-11 [11815854] Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3052-7 [11867750] J Allergy Clin Immunol. 2002 Apr;109(4):649-57 [11941315] J Ind Microbiol Biotechnol. 2002 Apr;28(4):232-8 [11986925] J Cell Biochem. 2002;86(2):357-64 [12112005] Science. 2002 Sep 20;297(5589):2048-51 [12202685] Clin Exp Immunol. 2003 Feb;131(2):217-24 [12562380] Proc Natl Acad Sci U S A. 1966 Jul;56(1):296-303 [4381784] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Infect Immun. 1984 Sep;45(3):761-7 [6432700] Infect Immun. 1986 Mar;51(3):795-800 [3081444] J Biol Chem. 1986 Jun 5;261(16):7123-6 [3711080] J Exp Med. 1989 Feb 1;169(2):431-45 [2783450] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2209-13 [2467303] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2374-8 [2538840] Infect Immun. 1989 Jul;57(7):2107-14 [2499545] J Biol Chem. 1989 Jul 5;264(19):11099-102 [2500434] Pharmacol Biochem Behav. 1990 Jul;36(3):515-9 [2377652] EMBO J. 1990 Sep;9(9):2827-34 [2118106] Cell. 1990 Sep 21;62(6):1217-26 [2169353] Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2274-7 [1900940] Infect Immun. 1991 Oct;59(10):3472-7 [1910002] Infect Immun. 1992 Jul;60(7):2581-7 [1612727] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10277-81 [1438214] Infect Immun. 1994 Jul;62(7):2958-62 [8005682] Mol Microbiol. 1994 Sep;13(6):1093-100 [7854123] J Biol Chem. 1995 Aug 4;270(31):18626-30 [7543106] Mol Med. 1994 Nov;1(1):7-18 [8790597] Mol Cell Biol. 1997 Jul;17(7):3947-54 [9199329] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2050-5 [9482836] Science. 1998 May 1;280(5364):734-7 [9563949] Biochemistry. 1998 Nov 10;37(45):15737-46 [9843379] Infect Immun. 1999 Apr;67(4):1853-9 [10085027] J Immunol. 1999 Mar 15;162(6):3527-33 [10092810] Infect Immun. 1999 Jun;67(6):3055-60 [10338520] Trends Microbiol. 1999 May;7(5):180-2 [10383221] J Appl Microbiol. 1999 Aug;87(2):285-7 [10475969] J Appl Microbiol. 1999 Aug;87(2):289-93 [10475971] Protein Expr Purif. 2000 Apr;18(3):293-302 [10733882] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulated over-expression of DNA polymerase beta mediates early onset cataract in mice. AN - 73222015; 12713817 AB - Base excision repair (BER) is a tightly coordinated mechanism for repair of DNA base damage (via alkylation and oxidation) and base loss. From E. coli to yeast to human cells, subtle alterations in expression of BER proteins lead to mutagenic or genome instability phenotypes. DNA polymerase beta (beta-pol), the major BER polymerase, has been found to be over-expressed in human tumor tissues and more recently it has been shown that over-expression of beta-pol results in a mutator and genome instability phenotype. These previous reports imply that beta-pol over-expression is deleterious and suggests that such an imbalance may cause an overall functional deficiency in the BER pathway. In the present study, we have developed a bicistronic tetracycline-responsive transgenic system to over-express beta-pol in mice. We find that over-expression of beta-pol in the lens epithelium results in the early onset of severe cortical cataract, with cataractogenesis beginning within 4 days after birth. In utero and post-natal suppression of transgenic Flag-beta-pol expression by doxycycline administration completely prevents cataract formation through adulthood, yet cataract is subsequently observed following removal of doxycycline and re-expression of the transgene. Cataract development accompanies increased expression of cyclooxygenase-2 in the lenticular fibers of the lens, implicating oxidative stress in the development of this cataractous phenotype. Although the mechanism for the transgene mediated cataractogenesis is not clear at this time, it is nevertheless intriguing that increased expression of beta-pol leads to such a phenotype. These results suggest that either a beta-pol expression imbalance negatively affects overall fidelity and/or BER capacity or that beta-pol has a role in lens epithelial cell differentiation. JF - DNA repair AU - Sobol, Robert W AU - Foley, Julie F AU - Nyska, Abraham AU - Davidson, Michael G AU - Wilson, Samuel H AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. rws9@pitt.edu Y1 - 2003/05/13/ PY - 2003 DA - 2003 May 13 SP - 609 EP - 622 VL - 2 IS - 5 SN - 1568-7864, 1568-7864 KW - Anti-Bacterial Agents KW - 0 KW - Isoenzymes KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Doxycycline KW - N12000U13O KW - Index Medicus KW - Animals KW - Escherichia coli -- metabolism KW - DNA Repair KW - Models, Molecular KW - Transgenes KW - Anti-Bacterial Agents -- pharmacology KW - Doxycycline -- pharmacology KW - Cell Differentiation KW - Mice KW - Mice, Transgenic KW - Models, Biological KW - Phenotype KW - Epithelial Cells -- cytology KW - Base Pair Mismatch KW - Isoenzymes -- biosynthesis KW - Oxidative Stress KW - Time Factors KW - Immunohistochemistry KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Cataract -- metabolism KW - DNA Polymerase beta -- genetics KW - DNA Polymerase beta -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73222015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=DNA+repair&rft.atitle=Regulated+over-expression+of+DNA+polymerase+beta+mediates+early+onset+cataract+in+mice.&rft.au=Sobol%2C+Robert+W%3BFoley%2C+Julie+F%3BNyska%2C+Abraham%3BDavidson%2C+Michael+G%3BWilson%2C+Samuel+H&rft.aulast=Sobol&rft.aufirst=Robert&rft.date=2003-05-13&rft.volume=2&rft.issue=5&rft.spage=609&rft.isbn=&rft.btitle=&rft.title=DNA+repair&rft.issn=15687864&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-14 N1 - Date created - 2003-04-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - SHED: Stem cells from human exfoliated deciduous teeth AN - 18745241; 5626017 AB - To isolate high-quality human postnatal stem cells from accessible resources is an important goal for stem-cell research. In this study we found that exfoliated human deciduous tooth contains multipotent stem cells [stem cells from human exfoliated deciduous teeth (SHED)]. SHED were identified to be a population of highly proliferative, clonogenic cells capable of differentiating into a variety of cell types including neural cells, adipocytes, and odontoblasts. After in vivo transplantation, SHED were found to be able to induce bone formation, generate dentin, and survive in mouse brain along with expression of neural markers. Here we show that a naturally exfoliated human organ contains a population of stem cells that are completely different from previously identified stem cells. SHED are not only derived from a very accessible tissue resource but are also capable of providing enough cells for potential clinical application. Thus, exfoliated teeth may be an unexpected unique resource for stem-cell therapies including autologous stem-cell transplantation and tissue engineering. JF - Proceedings of the National Academy of Sciences, USA AU - Miura, M AU - Gronthos, S AU - Zhao, M AU - Lu, B AU - Fisher, L W AU - Robey, P G AU - Shi, S AD - Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, sshi@dir.nidcr.nih.gov Y1 - 2003/05/13/ PY - 2003 DA - 2003 May 13 SP - 5807 EP - 5812 VL - 100 IS - 10 SN - 0027-8424, 0027-8424 KW - man KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W 30965:Miscellaneous, Reviews KW - W3 33220:Cell culture KW - W4 110:Biomedical Materials & Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18745241?accountid=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=SHED%3A+Stem+cells+from+human+exfoliated+deciduous+teeth&rft.au=Miura%2C+M%3BGronthos%2C+S%3BZhao%2C+M%3BLu%2C+B%3BFisher%2C+L+W%3BRobey%2C+P+G%3BShi%2C+S&rft.aulast=Miura&rft.aufirst=M&rft.date=2003-05-13&rft.volume=100&rft.issue=10&rft.spage=5807&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.0937635100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.0937635100 ER - TY - JOUR T1 - Ultra-high-pressure inactivation of prion infectivity in processed meat: A practical method to prevent human infection AN - 18743216; 5626067 AB - Bovine spongiform encephalopathy contamination of the human food chain most likely resulted from nervous system tissue in mechanically recovered meat used in the manufacture of processed meats. We spiked hot dogs with 263K hamster-adapted scrapie brain (10% wt/wt) to produce an infectivity level of [approx]9 log sub(10) mean lethal doses (LD sub(50)) per g of paste homogenate. Aliquots were subjected to short pressure pulses of 690, 1,000, and 1,200 MPa at running temperatures of 121-137 degree C. Western blots of PrPres were found to be useful indicators of infectivity levels, which at all tested pressures were significantly reduced as compared with untreated controls: from [approx]10 super(3) LD sub(50) per g at 690 MPa to [approx]10 super(6) LD sub(50) per g at 1,200 MPa. The application of commercially practical conditions of temperature and pressure could ensure the safety of processed meats from bovine spongiform encephalopathy contamination, and could also be used to study phase transitions of the prion protein from its normal to misfolded state. JF - Proceedings of the National Academy of Sciences, USA AU - Brown, P AU - Meyer, R AU - Cardone, F AU - Pocchiari, M AD - National Institutes of Health, Bethesda, MD 20892, brownp@ninds.nih.gov Y1 - 2003/05/13/ PY - 2003 DA - 2003 May 13 SP - 6093 EP - 6097 VL - 100 IS - 10 SN - 0027-8424, 0027-8424 KW - Bovine spongiform encephalopathy KW - hamsters KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - V 22130:Diseases associated with slow viruses KW - A 01114:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18743216?accountid=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=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Ultra-high-pressure+inactivation+of+prion+infectivity+in+processed+meat%3A+A+practical+method+to+prevent+human+infection&rft.au=Brown%2C+P%3BMeyer%2C+R%3BCardone%2C+F%3BPocchiari%2C+M&rft.aulast=Brown&rft.aufirst=P&rft.date=2003-05-13&rft.volume=100&rft.issue=10&rft.spage=6093&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.1031826100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.1031826100 ER - TY - JOUR T1 - Scission, spores, and apoptosis: a proposal for the evolutionary origin of mitochondria in cell death induction AN - 21329946; 5643906 AB - Mitochondria fragment prior to caspase activation during many pathways of apoptosis. Inhibition of the machinery that normally regulates mitochondrial morphology in healthy cells inhibits the fission that occurs during apoptosis and actually delays the process of cell death. Interestingly, there are certain parallels between mitochondrial fission and bacterial sporulation. As bacterial sporulation can be considered a stress response we suggest that a primordial stress response of endosymbiont mitochondrial progenitors may have been adopted for the stress response of early eukaryotes. Thus, the mitochondrial fission process may represent an early stress response of primitive mitochondria that could have integrated the stress signals and acted as an initial sensor for the eukaryotic response system. The fact that mitochondria fragment during apoptosis using the machinery descended from or that superceded the bacterial stress response of sporulation is consistent with this hypothesis. This hypothesis would explain why what is generally considered the 'power house' of the cell came to integrate the cell death response and regulate apoptosis. JF - Biochemical and Biophysical Research Communications AU - Frank, S AU - Robert, E G AU - Youle, R J AD - Biochemistry Section, SNB, NINDS, NIH, Building 10, Room 5D-37, Bethesda, MD 20892, USA, Youle@helix.nih.gov Y1 - 2003/05/09/ PY - 2003 DA - 2003 May 09 SP - 481 EP - 486 PB - Elsevier Science (USA) VL - 304 IS - 3 SN - 0006-291X, 0006-291X KW - Microbiology Abstracts B: Bacteriology KW - Stem cells KW - Houses KW - Apoptosis KW - Endosymbionts KW - Sporulation KW - Mitochondria KW - Stress KW - Cytology KW - Caspase KW - Spores KW - Evolution KW - J 02430:Symbiosis, Antibiosis & Phages UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21329946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Scission%2C+spores%2C+and+apoptosis%3A+a+proposal+for+the+evolutionary+origin+of+mitochondria+in+cell+death+induction&rft.au=Frank%2C+S%3BRobert%2C+E+G%3BYoule%2C+R+J&rft.aulast=Frank&rft.aufirst=S&rft.date=2003-05-09&rft.volume=304&rft.issue=3&rft.spage=481&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/10.1016%2FS0006-291X%2803%2900620-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Houses; Stem cells; Apoptosis; Endosymbionts; Sporulation; Cytology; Stress; Mitochondria; Caspase; Spores; Evolution DO - http://dx.doi.org/10.1016/S0006-291X(03)00620-X ER - TY - JOUR T1 - Stem Cell Programs AN - 18754080; 5626261 AB - The U.S. National Institutes of Health place a high priority on support for research using human embryonic stem cells, as well as other types of stem cells, that will also be useful for basic, translational, and clinical studies. Research using human embryonic stem cells offers the potential to inform us about the earliest molecular and cellular processes that regulate normal development and provides a tool to discover how a cell is able to be both pluripotent and indefinitely self-renewing. In addition, research using human embryonic stem cells will help the scientific community to understand the molecular signals that specify differentiation into specific cell types, some of which may ultimately be useful for cell-based treatment of disorders that involve loss of a specific cell type (such as type 1 diabetes or Parkinson's disease, to cite two of many examples). We are in the very early stages of understanding what can be accomplished with human embryonic stem cells. There are many basic research studies that need to be performed before we can begin clinical trials involving specialized cells differentiated from human embryonic stem cells. We need to understand how to drive differentiation along specific pathways, to establish techniques for isolating specific cell types, to control cell proliferation, and to control interactions between the host immune system and transplanted cells that might mediate graft rejection. The long-term stability of transplanted cells will need to be assessed. JF - Science (Washington) AU - Zerhouni, E AD - National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2003/05/09/ PY - 2003 DA - 2003 May 09 SP - 911 EP - 912 PB - American Association for the Advancement of Science VL - 300 IS - 5621 SN - 0036-8075, 0036-8075 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts 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/18754080?accountid=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=Science+%28Washington%29&rft.atitle=Stem+Cell+Programs&rft.au=Zerhouni%2C+E&rft.aulast=Zerhouni&rft.aufirst=E&rft.date=2003-05-09&rft.volume=300&rft.issue=5621&rft.spage=911&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Identification of cJun-responsive genes in Rat-1a cells using multiple techniques: increased expression of stathmin is necessary for cJun-mediated anchorage-independent growth. AN - 73286942; 12743595 AB - cJun is a major component of the transcription factor AP-1 and mediates a diverse set of biologic properties including proliferation, differentiation, and apoptosis. To identify cJun-responsive genes, we inducibly expressed cJun in Rat-1a cells and observed two distinct phenotypes: changes in cellular morphology with adherent growth and anchorage-independent growth. The biologic effects of cJun were entirely reversible demonstrating that they require the continued presence of cJun. To determine the genes, which mediate the biologic effects of cJun, we employed multiple methods including differential gene analysis, suppression subtractive hybridization, and cDNA microarrays. We identified 38 cJun-responsive genes including three uncharacterized genes under adherent and/or nonadherent conditions. Half of the known 36 genes were cytoskeleton- and adhesion-related genes, suggesting a major role of cJun in the regulation of the genes related to cell morphology. As proof of the principle that this approach could identify genes whose upregulation was necessary for nonadherent growth, we investigated one gene, stathmin whose upregulation by cJun was observed only under these conditions. Although overexpression of stathmin did not result in nonadherent growth, inhibition of stathmin protein expression by antisense oligonucleotides in cJun-induced Rat-1a cells prevented nonadherent growth. These results suggest that stathmin plays an essential role in anchorage-independent growth by cJun and may be a potential target for specific inhibitors for AP-1-dependent processes involved in carcinogenesis. JF - Oncogene AU - Kinoshita, Ichiro AU - Leaner, Virna AU - Katabami, Motoo AU - Manzano, Ramon G AU - Dent, Paul AU - Sabichi, Anita AU - Birrer, Michael J AD - Cell and Cancer Biology Department, Center For Cancer Research, National Cancer Institute, Rockville, MD 20850, USA. Y1 - 2003/05/08/ PY - 2003 DA - 2003 May 08 SP - 2710 EP - 2722 VL - 22 IS - 18 SN - 0950-9232, 0950-9232 KW - DNA Primers KW - 0 KW - Luminescent Proteins KW - Microtubule Proteins KW - Phosphoproteins KW - Proto-Oncogene Proteins c-jun KW - Stathmin KW - Transcription Factors KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Doxorubicin KW - 80168379AG KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - Binding Sites KW - Rats KW - Mutagenesis, Site-Directed KW - Rats, Inbred F344 KW - Promoter Regions, Genetic KW - Base Sequence KW - Doxorubicin -- pharmacology KW - Transfection KW - Kinetics KW - Molecular Sequence Data KW - Genes, Reporter KW - Gene Expression Regulation -- drug effects KW - Luciferases -- genetics KW - Luminescent Proteins -- genetics KW - Cell Line KW - Cell Division KW - Phosphoproteins -- genetics KW - Proto-Oncogene Proteins c-jun -- genetics KW - Genes, jun UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73286942?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+of+cJun-responsive+genes+in+Rat-1a+cells+using+multiple+techniques%3A+increased+expression+of+stathmin+is+necessary+for+cJun-mediated+anchorage-independent+growth.&rft.au=Kinoshita%2C+Ichiro%3BLeaner%2C+Virna%3BKatabami%2C+Motoo%3BManzano%2C+Ramon+G%3BDent%2C+Paul%3BSabichi%2C+Anita%3BBirrer%2C+Michael+J&rft.aulast=Kinoshita&rft.aufirst=Ichiro&rft.date=2003-05-08&rft.volume=22&rft.issue=18&rft.spage=2710&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-27 N1 - Date created - 2003-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of Investigational Radiation Modifiers AN - 221022194; 12734315 AB - Whenever potentially curative therapy is available, the base therapy to which the radiation modifier is added should not be compro-mised. The issues surrounding the decision to add an investigational radiation modifier to radiation alone versus adding a radiation modifier to definitive chemotherapy and radiation aredependent upon the toxicities and efficacy of the current standard for the underlying disease being treated. JF - Journal of the National Cancer Institute AU - Colevas, A Dimitrios AU - J. Martin Brown AU - Hahn, Stephen AU - Mitchell, James AU - Camphausen, Kevin AU - Coleman, C Norman Y1 - 2003/05/07/ PY - 2003 DA - 2003 May 07 SP - 646 EP - 51 CY - Oxford PB - Oxford Publishing Limited(England) VL - 95 IS - 9 SN - 00278874 KW - Medical Sciences--Oncology KW - Antineoplastic Agents KW - Drugs, Investigational KW - Radiation-Sensitizing Agents KW - Amifostine KW - Radiation KW - Cancer KW - United States KW - Amifostine -- pharmacology KW - Animals KW - Clinical Trials, Phase II as Topic KW - Humans KW - Clinical Trials, Phase I as Topic KW - National Institutes of Health (U.S.) KW - Critical Pathways KW - Neoplasms, Experimental -- radiotherapy KW - Neoplasms, Experimental -- drug therapy KW - Research Design KW - Antineoplastic Agents -- pharmacology KW - Neoplasms -- drug therapy KW - Drugs, Investigational -- pharmacology KW - Neoplasms -- radiotherapy KW - Radiation-Sensitizing Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/221022194?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Development+of+Investigational+Radiation+Modifiers&rft.au=Colevas%2C+A+Dimitrios%3BJ.+Martin+Brown%3BHahn%2C+Stephen%3BMitchell%2C+James%3BCamphausen%2C+Kevin%3BColeman%2C+C+Norman&rft.aulast=Colevas&rft.aufirst=A&rft.date=2003-05-07&rft.volume=95&rft.issue=9&rft.spage=646&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright Oxford University Press(England) May 7, 2003 N1 - Last updated - 2014-05-15 N1 - CODEN - JNCIEQ ER - TY - JOUR T1 - Early or late appearance of "dropped head syndrome" in amyotrophic lateral sclerosis. AN - 85269333; pmid-12700323 AB - BACKGROUND: "Dropped head syndrome" caused by neck extensor weakness has been reported in a variety of neuromuscular disorders. Previously published reports include isolated cases with amyotrophic lateral sclerosis (ALS). In this report, nine patients with ALS and dropped head syndrome seen during a 20 year period are described. PATIENTS AND INVESTIGATIONS: Between 1981 and 2000, 683 patients with ALS were diagnosed, based on El Escorial criteria. Nine of these had profound neck extensor weakness observed as an early feature, or developing during the later stages of the disease. The protocol for evaluation included detailed clinical history, neurological examination, electromyography, and nerve conduction studies. Investigations were undertaken to exclude malignancy, lymphoproliferative disorders, thyroid dysfunction, and collagen vascular disease. RESULTS: The incidence of dropped head syndrome was 1.3%. The mean (SD) age of the affected patients was 53.3 (10.3) years (range 33 to 65), with an equal distribution of cases in the fourth to seventh decades. In six patients, head drop was an early feature (mean interval from onset of illness 11.6 months (range 3 to 24)); in three it was late (between three and eight years after onset). In five patients, mild neck flexor weakness was present in addition to severe extensor weakness. In all nine patients there were diffuse upper and lower motor neurone signs. None of the patients had difficulty in breathing but all had difficulty in swallowing and social embarrassment, both of which could be corrected by simple measures. CONCLUSIONS: Dropped head syndrome is an important clinical sign and usually occurs as an early feature within the first one to two years after the onset of ALS. The cause of dropped head syndrome in these nine cases could be easily established as ALS by the presence of generalised signs. JF - Journal of Neurology, Neurosurgery, and Psychiatry AU - Gourie-Devi, M AU - Nalini, A AU - Sandhya, S AD - Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. PY - 2003 SP - 683 EP - 686 VL - 74 IS - 5 SN - 0022-3050, 0022-3050 KW - Head KW - Human KW - Aged KW - Muscle Weakness KW - Neck KW - Amyotrophic Lateral Sclerosis KW - Syndrome KW - Adult KW - Middle Age KW - Posture KW - Time Factors KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85269333?accountid=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+Neurology%2C+Neurosurgery%2C+and+Psychiatry&rft.atitle=Early+or+late+appearance+of+%22dropped+head+syndrome%22+in+amyotrophic+lateral+sclerosis.&rft.au=Gourie-Devi%2C+M%3BNalini%2C+A%3BSandhya%2C+S&rft.aulast=Gourie-Devi&rft.aufirst=M&rft.date=2003-05-01&rft.volume=74&rft.issue=5&rft.spage=683&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurology%2C+Neurosurgery%2C+and+Psychiatry&rft.issn=00223050&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. AN - 85265011; pmid-12724779 AB - In mammals, an example of planar cell polarity (PCP) is the uniform orientation of the hair cell stereociliary bundles within the cochlea. The PCP pathway of Drosophila refers to a conserved signalling pathway that regulates the coordinated orientation of cells or structures within the plane of an epithelium. Here we show that a mutation in Vangl2, a mammalian homologue of the Drosophila PCP gene Strabismus/Van Gogh, results in significant disruptions in the polarization of stereociliary bundles in mouse cochlea as a result of defects in the direction of movement and/or anchoring of the kinocilium within each hair cell. Similar, but less severe, defects are observed in animals containing a mutation in the LAP protein family gene Scrb1 (homologous with Drosophila scribble). Polarization defects in animals heterozygous for Vangl2 and Scrb1 are comparable with Vangl2 homozygotes, demonstrating genetic interactions between these genes in the regulation of PCP in mammals. These results demonstrate a role for the PCP pathway in planar polarization in mammals, and identify Scrb1 as a PCP gene. JF - Nature AU - Montcouquiol Mireille AU - Rachel, Rivka A AU - Lanford, Pamela J AU - Copeland, Neal G AU - Jenkins, Nancy A AU - Kelley, Matthew W AD - Section on Developmental Neuroscience, NIDCD, National Institutes of Health, Rockville, Maryland 20850, USA.; Department of Cell Biology, School of Medicine, Georgetown University Medical Center, Georgetown University PY - 2003 SP - 173 EP - 177 VL - 423 IS - 6936 SN - 0028-0836, 0028-0836 KW - Genotype KW - Animals KW - Support, U.S. Gov't, P.H.S. KW - Hair Cells KW - Molecular Sequence Data KW - Mice KW - Protein Structure, Tertiary KW - Temporal Bone KW - Mutation KW - Membrane Proteins KW - Nerve Tissue Proteins KW - Mice, Knockout KW - Cell Polarity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85265011?accountid=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=Nature&rft.atitle=Identification+of+Vangl2+and+Scrb1+as+planar+polarity+genes+in+mammals.&rft.au=Montcouquiol+Mireille%3BRachel%2C+Rivka+A%3BLanford%2C+Pamela+J%3BCopeland%2C+Neal+G%3BJenkins%2C+Nancy+A%3BKelley%2C+Matthew+W&rft.aulast=Montcouquiol+Mireille&rft.aufirst=&rft.date=2003-05-01&rft.volume=423&rft.issue=6936&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Role of the hippocampal system in associative learning beyond the spatial domain. AN - 85238292; pmid-12690059 AB - Expert opinion remains divided on the issue of whether the hippocampal system functions exclusively in spatial information processing, e.g. in navigation or in understanding spatial relations, or whether it plays a more general role in higher brain function. Previous work on monkeys and rats has tended to support the former view, whereas observations in the clinic point to the latter, including functions as diverse as declarative knowledge, episodic memory, word learning, and understanding relations among objects. One influential theory posits a general role for the hippocampal system in associative learning, with emphasis on associations learned rapidly and recently. The results presented here are consistent with this theory, along with previous clinical and theoretical studies indicating that the hippocampal system is necessary for associative learning even if no component of the association relies on spatial information. In the study reported here, rhesus monkeys learned a series of conditional stimulus-response associations involving complex visual stimuli presented on a video monitor. Each stimulus instructed one of three responses: tapping the stimulus with the hand, steady hand contact with the stimulus for a brief period of time, or steady contact for a longer time. Fornix transection impaired the learning of these associations, even though both the stimuli and the responses were nonspatially differentiated, and this deficit persisted for at least 2 years. This finding indicates that the hippocampal system plays an important role in associative learning regardless of the relevance of spatial information to any aspect of the association. Fornix-transected monkeys were impaired in learning new stimulus-response associations even when the stimuli were highly familiar. Thus, the deficit was one of associating each stimulus with a response, as opposed to problems in distinguishing the stimuli from each other. In contrast to these effects, fornix transection did not impair performance when familiar stimuli instructed a response according to an already-learned association, which shows that the deficit was one of learning new associations rather than one of retention or retrieval of previously learned ones. Taken together, these results show that fornix transection causes a long-lasting impairment in associative learning outside of the spatial domain, in a manner consistent with theories of hippocampal-system function that stress a general role in the rapid acquisition of associative knowledge. JF - Brain AU - Brasted, P J AU - Bussey, T J AU - Murray, E A AU - Wise, S P AD - Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, MD 20892-4401, USA. PY - 2003 SP - 1202 EP - 1223 VL - 126 IS - Pt 5 SN - 0006-8950, 0006-8950 KW - Fornix (Brain) KW - Brain Mapping KW - Memory KW - Hippocampus KW - Association Learning KW - Computer Graphics KW - Animal KW - Support, Non-U.S. Gov't KW - Macaca mulatta KW - Neuropsychological Tests KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85238292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain&rft.atitle=Role+of+the+hippocampal+system+in+associative+learning+beyond+the+spatial+domain.&rft.au=Brasted%2C+P+J%3BBussey%2C+T+J%3BMurray%2C+E+A%3BWise%2C+S+P&rft.aulast=Brasted&rft.aufirst=P&rft.date=2003-05-01&rft.volume=126&rft.issue=Pt+5&rft.spage=1202&rft.isbn=&rft.btitle=&rft.title=Brain&rft.issn=00068950&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - MRI detection of ferritin iron overload and associated neuronal pathology in iron regulatory protein-2 knockout mice. AN - 85237507; pmid-12691842 AB - Genetic ablation of iron regulatory protein 2 (IRP-2), a protein responsible for post-transcriptional regulation of expression of several iron metabolism proteins, predisposes IRP-2 -/- mice to develop adult onset neurodegenerative disease. Ferric iron reproducibly accumulates within axonal tracts and neuronal cell bodies in discrete regions of the brain, and areas of iron accumulation colocalize with areas of high ferritin expression. To better evaluate the onset and progression of neurodegeneration in IRP-2 -/- mice, we performed a high-resolution magnetic resonance imaging study comparing live, age-matched wild-type and IRP-2 -/- mice, using an 11.7-Tesla magnet and a custom-designed head coil. The mice were perfused after imaging, and iron stains and immunohistochemical studies were performed. We detected increases in the number of pixels with low T(2) values expected from accumulations of iron in IRP-2 -/- mice. Moreover, in several areas of the brain, including the substantia nigra and the superior colliculus, we detected areas with unusually high T(2) values that likely represented accumulation of water. On histopathological examination we discovered relatively small vacuoles in these brain regions of IRP-2 -/- mice. Our ability to gather T(2) data within regions of interest enabled us to define a bimodal T(2) intensity pattern that likely represents both ferritin iron accumulation and its associated pathological consequences within the brain. Our discoveries may have significant applications for the diagnosis and treatment of human diseases if such high-resolution techniques can be adapted for use in human subjects. JF - Brain Research AU - Grabill Colette AU - Silva, Afonso C AU - Smith, Sophia S AU - Koretsky, Alan P AU - Rouault, Tracey A AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bldg. 18T, Room 101 9000 Rockville Pike, 20892, Bethesda, MD, USA PY - 2003 SP - 95 EP - 106 VL - 971 IS - 1 SN - 0006-8993, 0006-8993 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85237507?accountid=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+Research&rft.atitle=MRI+detection+of+ferritin+iron+overload+and+associated+neuronal+pathology+in+iron+regulatory+protein-2+knockout+mice.&rft.au=Grabill+Colette%3BSilva%2C+Afonso+C%3BSmith%2C+Sophia+S%3BKoretsky%2C+Alan+P%3BRouault%2C+Tracey+A&rft.aulast=Grabill+Colette&rft.aufirst=&rft.date=2003-05-01&rft.volume=971&rft.issue=1&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Morphogenesis and dysmorphogenesis of the appendicular skeleton. AN - 73619641; 12955856 AB - Cartilage patterning and differentiation are prerequisites for skeletal development through endochondral ossification (EO). Multipotential mesenchymal cells undergo a complex process of cell fate determination to become chondroprogenitors and eventually differentiate into chondrocytes. These developmental processes require the orchestration of cell-cell and cell-matrix interactions. In this review, we present limb bud development as a model for cartilage patterning and differentiation. We summarize the molecular and cellular events and signaling pathways for axis patterning, cell condensation, cell fate determination, digit formation, interdigital apoptosis, EO, and joint formation. The interconnected nature of these pathways underscores the effects of genetic and teratogenic perturbations that result in skeletal birth defects. The topics reviewed also include limb dysmorphogenesis as a result of genetic disorders and environmental factors, including FGFR, GLI3, GDF5/CDMP1, Sox9, and Cbfa1 mutations, as well as thalidomide- and alcohol-induced malformations. Understanding the complex interactions involved in cartilage development and EO provides insight into mechanisms underlying the biology of normal cartilage, congenital disorders, and pathologic adult cartilage. JF - Birth defects research. Part C, Embryo today : reviews AU - Shum, Lillian AU - Coleman, Cynthia M AU - Hatakeyama, Yuji AU - Tuan, Rocky S AD - Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Building 50, Room 1503, MSC 8022, Bethesda, MD 20892, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 102 EP - 122 VL - 69 IS - 2 SN - 1542-975X, 1542-975X KW - Index Medicus KW - Animals KW - Chondrogenesis -- physiology KW - Humans KW - Osteogenesis KW - Extremities -- embryology KW - Bone and Bones -- abnormalities KW - Body Patterning -- physiology KW - Bone Development -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73619641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Birth+defects+research.+Part+C%2C+Embryo+today+%3A+reviews&rft.atitle=Morphogenesis+and+dysmorphogenesis+of+the+appendicular+skeleton.&rft.au=Shum%2C+Lillian%3BColeman%2C+Cynthia+M%3BHatakeyama%2C+Yuji%3BTuan%2C+Rocky+S&rft.aulast=Shum&rft.aufirst=Lillian&rft.date=2003-05-01&rft.volume=69&rft.issue=2&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Birth+defects+research.+Part+C%2C+Embryo+today+%3A+reviews&rft.issn=1542975X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-06 N1 - Date created - 2003-09-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - EEG deficits in chronic marijuana abusers during monitored abstinence: preliminary findings. AN - 73452778; 12853297 AB - Cognitive, cerebrovascular, and psychiatric impairments have been documented with chronic marijuana users. To better understand the nature and duration of these neurocognitive changes in marijuana abusers, we recorded the resting EEG of 29 abstinent chronic marijuana abusers and 21 control subjects. The marijuana abusers were tested twice: the first evaluation occurred within 72 hours of admission to the inpatient research unit; the second evaluation occurred after 28 to 30 days of monitored abstinence. A three-minute period of EEG was recorded during resting eyes-closed conditions from eight electrodes (F(3), C(3), P(3), O(1), F(4), C(4), P(4), and O(2)). The artifacted EEG was converted to six frequency bands (delta, theta, alpha(1), alpha(2), beta(1), and beta(2)) using a fast Fourier transform. During early abstinence, absolute power was significantly lower (p < 0.05) for the marijuana abusers than for the control subjects for the theta and alpha(1) bands. These reductions in theta and alpha(1) power persisted for 28 days of monitored abstinence. These EEG changes, together with cerebral blood flow deficits, might underlie the cognitive alterations observed in marijuana abusers. Additional research is needed to determine how long these deficits persist during abstinence and if treatment with neuroprotective agents may reverse them. JF - Annals of the New York Academy of Sciences AU - Herning, Ronald I AU - Better, Warren AU - Tate, Kimberly AU - Cadet, Jean L AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. rherning@intra.nida.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 75 EP - 8; discussion 79-81 VL - 993 SN - 0077-8923, 0077-8923 KW - Index Medicus KW - Humans KW - Cerebrovascular Circulation -- physiology KW - Adult KW - Male KW - Substance Withdrawal Syndrome -- physiopathology KW - Electroencephalography KW - Cannabis -- adverse effects KW - Marijuana Abuse -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73452778?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=EEG+deficits+in+chronic+marijuana+abusers+during+monitored+abstinence%3A+preliminary+findings.&rft.au=Herning%2C+Ronald+I%3BBetter%2C+Warren%3BTate%2C+Kimberly%3BCadet%2C+Jean+L&rft.aulast=Herning&rft.aufirst=Ronald&rft.date=2003-05-01&rft.volume=993&rft.issue=&rft.spage=75&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 - 2003-08-25 N1 - Date created - 2003-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Demographic and practice characteristics of psychiatrists who primarily treat patients with substance use disorders. AN - 73446260; 12851014 AB - This study examined the sociodemographic and practice characteristics of psychiatrists whose caseloads consist primarily of patients with Substance Use Disorders (SUD). A survey instrument was completed by a random sample of 865 psychiatrists. Study groups were defined as high-SUD providers if psychiatrists reported having 51% or more patients with SUD (n=92) and non-SUD providers as those who reported not having any patients with SUD (n=128). High-SUD providers tended to be younger, more likely to graduate from international medical schools, have larger caseloads, work more hours per week, and have a higher proportion of inpatients and publicly funded patients than non-SUD providers. Results suggest that psychiatrists who primarily treat patients with SUD are in their early careers and treat patients with more clinical, psychosocial, and economic disadvantages. The implications of these findings for psychiatry training programs and policy makers will be discussed. JF - The American journal on addictions AU - Montoya, Ivan D AU - Herbeck, Diane M AU - Svikis, Dace S AU - Fitek, Diana J AU - Marcus, Steven C AU - Pincus, Harold A AD - Division of Treatment Research and Development, National Institute on Drug Abuse, Bethesda, MD 20892, USA. imontoya@mail.nih.gov PY - 2003 SP - 181 EP - 192 VL - 12 IS - 3 SN - 1055-0496, 1055-0496 KW - Index Medicus KW - Demography KW - Workload KW - Health Care Surveys KW - Community Mental Health Services -- manpower KW - Humans KW - Adult KW - Middle Aged KW - Inpatients KW - Male KW - Female KW - Substance-Related Disorders -- therapy KW - Psychiatry -- statistics & numerical data KW - Psychiatry -- education KW - Practice Patterns, Physicians' -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73446260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+on+addictions&rft.atitle=Demographic+and+practice+characteristics+of+psychiatrists+who+primarily+treat+patients+with+substance+use+disorders.&rft.au=Montoya%2C+Ivan+D%3BHerbeck%2C+Diane+M%3BSvikis%2C+Dace+S%3BFitek%2C+Diana+J%3BMarcus%2C+Steven+C%3BPincus%2C+Harold+A&rft.aulast=Montoya&rft.aufirst=Ivan&rft.date=2003-05-01&rft.volume=12&rft.issue=3&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=The+American+journal+on+addictions&rft.issn=10550496&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-20 N1 - Date created - 2003-07-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Psychiatry. 1998 Mar;155(3):397-404 [9501752] Arch Gen Psychiatry. 1999 May;56(5):441-9 [10232299] Am J Geriatr Psychiatry. 1999 Fall;7(4):279-88 [10521159] Mt Sinai J Med. 2000 Oct-Nov;67(5-6):340-6 [11064484] J Clin Psychiatry. 2000 Sep;61(9):698-705; quiz 706 [11030495] Psychiatr Serv. 2000 Sep;51(9):1126-9 [10970914] J Stud Alcohol. 2000 May;61(3):427-30 [10807214] Psychiatr Serv. 1997 Dec;48(12):1606-7 [9406278] Am J Psychiatry. 1996 Jun;153(6):853-5 [8633726] Lancet. 1996 Jan 27;347(8996):237-40 [8551886] Acad Med. 1992 Oct;67(10):691-3 [1388535] J Addict Dis. 1993;12(4):162-6 [8292637] Am J Psychiatry. 1994 May;151(5):795-6 [8166344] J Addict Dis. 2002;21(1):5-19 [11831500] J Psychoactive Drugs. 2001 Jul-Sep;33(3):203-11 [11718313] Acad Med. 2001 May;76(5):410-8 [11346513] Am J Addict. 2001 Winter;10(1):40-7 [11268827] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Male reproductive effects of phthalates: an emerging picture. AN - 73411113; 12859023 JF - Epidemiology (Cambridge, Mass.) AU - Hoppin, Jane A AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA. hoppin1@niehs.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 259 EP - 260 VL - 14 IS - 3 SN - 1044-3983, 1044-3983 KW - Phthalic Acids KW - 0 KW - Dibutyl Phthalate KW - 2286E5R2KE KW - Diethylhexyl Phthalate KW - C42K0PH13C KW - Index Medicus KW - Animals KW - Humans KW - Diethylhexyl Phthalate -- toxicity KW - Infant, Newborn KW - Infertility, Male -- chemically induced KW - Dibutyl Phthalate -- toxicity KW - Male KW - Semen -- drug effects KW - Phthalic Acids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73411113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Male+reproductive+effects+of+phthalates%3A+an+emerging+picture.&rft.au=Hoppin%2C+Jane+A&rft.aulast=Hoppin&rft.aufirst=Jane&rft.date=2003-05-01&rft.volume=14&rft.issue=3&rft.spage=259&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-30 N1 - Date created - 2003-07-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Epidemiology. 2003 May;14(3):269-77 [12859026] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessing exposure to crystalline silica from farm work: a population-based study in the Southeastern United States. AN - 73409878; 12821278 AB - Farm workers are exposed to crystalline silica, but there are no established questionnaires to assess silica dust exposure from farm work in epidemiologic studies. This study examines aspects of farm work that were used to estimate potential silica dust exposure in a population-based study conducted in the southeastern United States. We collected work and farming histories through in-person interviews with 620 participants in a population-based case-control study of systemic lupus erythematosus. A dust-exposure matrix was used to develop a telephone interview for 69 participants with potential medium- or high-level exposure, including questions on tasks, frequency, and farm location. Soil systems maps were used to infer soil type (sandy/other). Exposure indices were constructed based on tasks, frequency, and soil type. Thirty-six percent of study participants worked on a farm, but only 52 (8%) were classified in the high (n=16) or medium (n=36) exposure groups based on responses to follow-up interview questions. Exposure indices based on open-ended job descriptions in initial interviews correctly categorized 52% of participants who answered prompted questions on relevant dusty tasks in follow-up interviews. Specific questions on dusty tasks and frequency are needed to accurately assess silica exposure from farm work. JF - Annals of epidemiology AU - Parks, Christine G AU - Cooper, Glinda S AU - Nylander-French, Leena A AU - Storm, Julia F AU - Archer, John D AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. parks@niehs.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 385 EP - 392 VL - 13 IS - 5 SN - 1047-2797, 1047-2797 KW - Air Pollutants, Occupational KW - 0 KW - Dust KW - Soil KW - Silicon Dioxide KW - 7631-86-9 KW - Index Medicus KW - Air Pollutants, Occupational -- poisoning KW - Humans KW - Retrospective Studies KW - Child KW - Southeastern United States KW - Adult KW - Case-Control Studies KW - Follow-Up Studies KW - Adolescent KW - Farmer's Lung KW - Female KW - Male KW - Occupational Exposure KW - Silicon Dioxide -- poisoning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73409878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Assessing+exposure+to+crystalline+silica+from+farm+work%3A+a+population-based+study+in+the+Southeastern+United+States.&rft.au=Parks%2C+Christine+G%3BCooper%2C+Glinda+S%3BNylander-French%2C+Leena+A%3BStorm%2C+Julia+F%3BArcher%2C+John+D&rft.aulast=Parks&rft.aufirst=Christine&rft.date=2003-05-01&rft.volume=13&rft.issue=5&rft.spage=385&rft.isbn=&rft.btitle=&rft.title=Annals+of+epidemiology&rft.issn=10472797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-28 N1 - Date created - 2003-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Smad3: a key player in pathogenetic mechanisms dependent on TGF-beta. AN - 73400409; 12814934 AB - Transforming growth factor-beta (TGF-beta), a key player in a large variety of physiological and disease processes, signals through transmembrane receptor serine/threonine kinases to activate novel signaling intermediates called Smad proteins, which then modulate transcription of target genes. We have utilized mice with a targeted deletion of Smad3, one of two homologous proteins involved in signaling from TGF-beta/activin, to investigate the function of this particular pathway in transducing such effects of TGF-beta. The dramatic results of the absence of Smad3 on parameters of healing of cutaneous wounds, such as reepithelialization and influx of inflammatory cells, as well as on fibrosis as modeled by radiation fibrosis of skin in mice, suggest that signaling flux through Smad3 is critical for chemotactic activity of TGF-beta, inhibitory effects of TGF-beta on keratinocyte proliferation and migration, and chemoattraction and elaboration of extracellular matrix by fibroblasts in fibrotic diseases. We recently identified a novel molecule, TLP for TRAP-1-like protein, which selectively interferes with Smad3 signaling, and are currently investigating whether levels of this protein might be altered in disease to change the relative flow of information from Smad2 and Smad3. JF - Annals of the New York Academy of Sciences AU - Roberts, Anita B AU - Russo, Angelo AU - Felici, Angelina AU - Flanders, Kathleen C AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20895-5055, USA. robertsa@dce41.nci.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 1 EP - 10 VL - 995 SN - 0077-8923, 0077-8923 KW - DNA-Binding Proteins KW - 0 KW - Smad2 Protein KW - Smad2 protein, mouse KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Animals KW - Disease Susceptibility KW - DNA Damage KW - Wound Healing KW - Mice KW - Models, Biological KW - Signal Transduction KW - Mice, Knockout KW - Transforming Growth Factor beta -- physiology KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73400409?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Smad3%3A+a+key+player+in+pathogenetic+mechanisms+dependent+on+TGF-beta.&rft.au=Roberts%2C+Anita+B%3BRusso%2C+Angelo%3BFelici%2C+Angelina%3BFlanders%2C+Kathleen+C&rft.aulast=Roberts&rft.aufirst=Anita&rft.date=2003-05-01&rft.volume=995&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-22 N1 - Date created - 2003-06-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Islet transplantation: where do we stand now? AN - 73342863; 12789649 AB - After many years of limited success in islet transplantation, researchers developing this procedure have made great strides, and several centers have now reported that islet transplantation can result in long-term insulin independence for patients with type 1 diabetes mellitus. The improved quality of life achieved in some islet allograft recipients suggests that this important line of investigation should proceed. Yet, several factors limit the technique and these hurdles must be overcome before it can be considered a practical treatment for the millions of individuals with diabetes, be it type 1 or type 2. Most obvious is the gross disparity between the number of islets available for clinical transplantation and the number of patients with diabetes who might benefit. Other important limitations, too often lost in the discussion, include complications associated with the technique itself, the toxicity of currently available immunosuppressive drugs, and the imperfect glycemia control achieved in most patients. In fact, our ongoing analysis as to whether transplantation-based therapy improves survival for patients with type 1 diabetes suggests that, for many at least, the opposite may be true. Two variables, as yet undefined, also need to be considered: (1) can the procedure, when done well, prevent or reverse diabetes-associated complications and (2) what are the long-term consequences of intrahepatic islets? Published in 2003 by John Wiley & Sons, Ltd. JF - Diabetes/metabolism research and reviews AU - Hirshberg, Boaz AU - Rother, Kristina I AU - Harlan, David M AD - Transplantation and Autoimmunity Branch, NIDDK/NIH/DHHS, Building 10, Room 11-S-219, Bethesda, MD 20892, USA. PY - 2003 SP - 175 EP - 8; discussion 175 VL - 19 IS - 3 SN - 1520-7552, 1520-7552 KW - Immunosuppressive Agents KW - 0 KW - Index Medicus KW - Humans KW - Immunosuppressive Agents -- adverse effects KW - Islets of Langerhans Transplantation -- trends KW - Islets of Langerhans Transplantation -- immunology KW - Diabetes Mellitus, Type 1 -- immunology KW - Islets of Langerhans Transplantation -- statistics & numerical data KW - Diabetes Mellitus, Type 1 -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73342863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes%2Fmetabolism+research+and+reviews&rft.atitle=Islet+transplantation%3A+where+do+we+stand+now%3F&rft.au=Hirshberg%2C+Boaz%3BRother%2C+Kristina+I%3BHarlan%2C+David+M&rft.aulast=Hirshberg&rft.aufirst=Boaz&rft.date=2003-05-01&rft.volume=19&rft.issue=3&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Diabetes%2Fmetabolism+research+and+reviews&rft.issn=15207552&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-22 N1 - Date created - 2003-06-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. AN - 73341121; 12771022 AB - Werner syndrome (WS) is a hallmark premature aging disease, in which the patients appear much older than their chronological age, and exhibit many of the clinical signs and symptoms of normal aging at an early stage in life. They develop many age-associated diseases early in life including atherosclerosis, osteoporosis, cataracts and display a high incidence of cancer. WS is also marked by increased genomic instability, manifested as chromosomal alterations. Characterization and study of the Werner protein (WRN) suggests that it participates in several important DNA metabolic pathways, and that its primary function may be in DNA repair processes. Thus, the WRN protein represents an important link between defective DNA repair and the processes related to aging and cancer. JF - Carcinogenesis AU - Opresko, Patricia L AU - Cheng, Wen-Hsing AU - von Kobbe, Cayetano AU - Harrigan, Jeanine A AU - Bohr, Vilhelm A AD - Laboratory of Molecular Gerontology, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 791 EP - 802 VL - 24 IS - 5 SN - 0143-3334, 0143-3334 KW - Exodeoxyribonucleases KW - EC 3.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - WRN protein, human KW - Werner Syndrome Helicase KW - Index Medicus KW - Humans KW - Aging -- physiology KW - DNA Repair KW - DNA Helicases -- physiology KW - Werner Syndrome -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73341121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Werner+syndrome+and+the+function+of+the+Werner+protein%3B+what+they+can+teach+us+about+the+molecular+aging+process.&rft.au=Opresko%2C+Patricia+L%3BCheng%2C+Wen-Hsing%3Bvon+Kobbe%2C+Cayetano%3BHarrigan%2C+Jeanine+A%3BBohr%2C+Vilhelm+A&rft.aulast=Opresko&rft.aufirst=Patricia&rft.date=2003-05-01&rft.volume=24&rft.issue=5&rft.spage=791&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-10 N1 - Date created - 2003-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Memory in pediatric patients undergoing conscious sedation for aversive medical procedures. AN - 73339709; 12790253 AB - This study investigated preserved memory in 26 pediatric cancer patients (65% boys, 77% Caucasian, mean age = 12.5 years) undergoing midazolam-induced conscious sedation during painful medical procedures to treat hematological or oncological diseases. The sedative midazolam had a significant anterograde amnesic effect on participants' performance on a visual recognition (explicit) memory task but not on a visual perceptual facilitation (implicit) memory task. That implicit memory scores were relatively unaffected while explicit memory scores deteriorated significantly indicates that leaning occurred while participants were sedated, even when participants did not recollect the learning event. These findings, which replicate those of M. R. Polster, R. A. McCarthy, G. O'Sullivan, P. A. Gray, and G. R. Park (1993) in a study of adults, have implications for the development and treatment of conditioned anxiety reactions associated with aversive medical procedures. JF - Health psychology : official journal of the Division of Health Psychology, American Psychological Association AU - Pringle, Beverly AU - Dahlquist, Lynnda M AU - Eskenazi, Allen AD - Department of Psychology, University of Maryland, Baltimore County, USA. bpringle@nida.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 263 EP - 269 VL - 22 IS - 3 SN - 0278-6133, 0278-6133 KW - Anesthetics, Intravenous KW - 0 KW - Midazolam KW - R60L0SM5BC KW - Index Medicus KW - Humans KW - Stress, Psychological KW - Child KW - Diagnostic Tests, Routine -- adverse effects KW - Adolescent KW - Male KW - Female KW - Conscious Sedation -- psychology KW - Pain -- prevention & control KW - Memory KW - Anesthetics, Intravenous -- pharmacology KW - Pain -- psychology KW - Midazolam -- adverse effects KW - Anesthetics, Intravenous -- adverse effects KW - Midazolam -- pharmacology KW - Amnesia, Retrograde -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73339709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Health+psychology+%3A+official+journal+of+the+Division+of+Health+Psychology%2C+American+Psychological+Association&rft.atitle=Memory+in+pediatric+patients+undergoing+conscious+sedation+for+aversive+medical+procedures.&rft.au=Pringle%2C+Beverly%3BDahlquist%2C+Lynnda+M%3BEskenazi%2C+Allen&rft.aulast=Pringle&rft.aufirst=Beverly&rft.date=2003-05-01&rft.volume=22&rft.issue=3&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Health+psychology+%3A+official+journal+of+the+Division+of+Health+Psychology%2C+American+Psychological+Association&rft.issn=02786133&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-04 N1 - Date created - 2003-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic aspects of susceptibility to air pollution. AN - 73329627; 12762575 AB - Inter-individual variation in human responses to air pollutants suggests that some subpopulations are at increased risk, and it is increasingly clear that genetic background is an important susceptibility factor. Genetically standardised animal models provide useful investigative tools. Linkage analyses using inbred mice identified chromosomal segments (quantitative trait loci (QTL)), with genes controlling susceptibility to the lung inflammatory (chromosome 17), injury (chromosome 11), and hyperpermeability (chromosome 4) responses to ozone (O3) exposure. An immune dysfunction response induced by exposure to sulphate-associated particles is linked to the identical chromosome 17 and 11 QTLs described for O3 susceptibility, thus similar genetic mechanisms may be controlling pulmonary responses to these pollutants. Candidate genes within the QTLs on chromosomes 4 and 17 include the toll-like receptor 4 and the pro-inflammatory cytokine, tumour necrosis factor-alpha, respectively. Functional analyses strongly support a role for these candidate genes in determining susceptibility to O3 and particulates. Because striking linkage homology exists between the human and mouse genomes, candidate susceptibility genes identified in the mouse are likely to aid research aimed at understanding human genetic factors that contribute to differential susceptibility. To date, no studies have examined the interaction between age and genetic background in the development of air pollution-induced lung disease. However, investigations have suggested an influence of age on genetic susceptibility to lung cancer and other diseases, which indicate that an interaction between age and genetic background may be important in air pollution disease pathogenesis. JF - The European respiratory journal. Supplement AU - Kleeberger, S R AD - Dept of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. kleeber1@niehs.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 52s EP - 56s VL - 40 SN - 0904-1850, 0904-1850 KW - Air Pollutants KW - 0 KW - Ozone KW - 66H7ZZK23N KW - Index Medicus KW - Genetic Linkage KW - Animals KW - Age Factors KW - Humans KW - Aged KW - Chromosome Mapping KW - Ozone -- adverse effects KW - Lung Diseases -- etiology KW - Lung Diseases -- genetics KW - Air Pollution -- adverse effects KW - Genetic Predisposition to Disease KW - Air Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73329627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+respiratory+journal.+Supplement&rft.atitle=Genetic+aspects+of+susceptibility+to+air+pollution.&rft.au=Kleeberger%2C+S+R&rft.aulast=Kleeberger&rft.aufirst=S&rft.date=2003-05-01&rft.volume=40&rft.issue=&rft.spage=52s&rft.isbn=&rft.btitle=&rft.title=The+European+respiratory+journal.+Supplement&rft.issn=09041850&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-29 N1 - Date created - 2003-05-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dysregulation of DNA repair pathways in a transforming growth factor alpha/c-myc transgenic mouse model of accelerated hepatocarcinogenesis. AN - 73305986; 12746474 AB - Previous work from our laboratory has implicated oxidative DNA damage and genetic instability in the etiology of transforming growth factor-alpha (TGFalpha)/c-myc-associated hepatocarcinogenesis. In contrast, oxidative DNA damage was lower in c-myc single-transgenic mice, consistent with less chromosomal damage and with later and more benign tumor formation. We examined whether defects in the DNA repair pathways contribute to the acceleration of liver cancer in TGFalpha/c-myc mice. A cDNA expression array containing 140 known genes and multiplex RT-PCR were used to compare the basal levels of expression of DNA repair genes at the dysplastic stage. Thirty-five percent (8/23) and 43% (10/23) of DNA repair genes were constitutively up-regulated in 10-week-old TGFalpha/c-myc and c-myc transgenic livers, respectively, compared with wild-type controls. The commonly up-regulated genes were OGG1 and NTH1 of base excision repair; ERCC5, RAD23A, and RAD23B of nucleotide excision repair; and RAD50, RAD52, and RAD54 involved in DNA strand break repair. Additional treatment with a peroxisome proliferator, Wy-14,643, known to increase the level of oxidants in the liver, failed to induce a further increase in the expression level of DNA repair enzymes in TGFalpha/c-myc but not in c-myc or wild-type livers. Moreover, expression of several genes, including Ku80, PMS2, and ATM, was decreased in TGFalpha/c-myc livers, suggesting a fault or inefficient activation of the DNA repair pathway upon induction of oxidative stress. Together, the results show that DNA damage response is attenuated in TGFalpha/c-myc mice, creating a condition that may contribute to acceleration of liver cancer in this model. JF - Laboratory investigation; a journal of technical methods and pathology AU - Hironaka, Koji AU - Factor, Valentina M AU - Calvisi, Diego F AU - Conner, Elizabeth A AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 643 EP - 654 VL - 83 IS - 5 SN - 0023-6837, 0023-6837 KW - Pyrimidines KW - 0 KW - Transforming Growth Factor alpha KW - pirinixic acid KW - 86C4MRT55A KW - Index Medicus KW - Animals KW - DNA Damage KW - Pyrimidines -- pharmacology KW - Disease Models, Animal KW - Mice KW - Gene Expression Regulation KW - Mice, Transgenic KW - Male KW - Hepatocytes -- metabolism KW - Liver Neoplasms -- pathology KW - DNA Repair KW - Transforming Growth Factor alpha -- genetics KW - Transforming Growth Factor alpha -- physiology KW - Liver Neoplasms -- etiology KW - Genes, myc -- physiology KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73305986?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Dysregulation+of+DNA+repair+pathways+in+a+transforming+growth+factor+alpha%2Fc-myc+transgenic+mouse+model+of+accelerated+hepatocarcinogenesis.&rft.au=Hironaka%2C+Koji%3BFactor%2C+Valentina+M%3BCalvisi%2C+Diego+F%3BConner%2C+Elizabeth+A%3BThorgeirsson%2C+Snorri+S&rft.aulast=Hironaka&rft.aufirst=Koji&rft.date=2003-05-01&rft.volume=83&rft.issue=5&rft.spage=643&rft.isbn=&rft.btitle=&rft.title=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-05 N1 - Date created - 2003-05-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Infant sleep position and associated health outcomes. AN - 73297953; 12742883 AB - The incidence of sudden infant death syndrome has decreased in the United States as the percentage of infants sleeping prone has decreased, but persisting concerns about the safety of supine sleeping likely contribute to prone sleeping prevalence rates that remain higher than 10%. To document health outcomes in infants aged 1 to 6 months in relation to sleep position. Prospective cohort study. Massachusetts and Ohio, from February 21, 1995, to December 31, 1998. A total of 3733 infants with consistent sleep positions at ages 1, 3, and 6 months. Descriptive statistics and multiple logistic regression analysis relating sleep position at each follow-up age to symptoms in the prior week (fever, cough, wheezing, stuffy nose, trouble breathing or sleeping, diarrhea, vomiting, or spitting up) and outpatient visits in the prior month (ear infection, breathing problem, vomiting, spitting up, colic, seizure, accident, or injury). No symptoms or outpatient visits were significantly more common among infants sleeping on the side or supine than in infants sleeping prone, and 3 symptoms were less common: (1) fever at 1 month in infants sleeping in the supine (adjusted odds ratio [OR], 0.56; 95% confidence interval [CI], 0.34-0.93) and side positions (OR, 0.48; 95% CI, 0.28-0.82); (2) stuffy nose at 6 months in the supine (OR, 0.74; 95% CI, 0.61-0.89) and side positions (OR, 0.82; 95% CI, 0.68-0.99); and (3) trouble sleeping at 6 months in the supine (OR, 0.57; 95% CI, 0.44-0.73) and side positions (OR, 0.69; 95% CI, 0.53-0.89). Also, outpatient visits for ear infections were less common at 3 and 6 months in infants sleeping in the supine position (OR, 0.64; 95% CI, 0.46-0.88; and OR, 0.73; 95% CI, 0.58-0.92, respectively) and at 3 months in the side position (OR, 0.68; 95% CI, 0.49-0.96). No identified symptom or illness was significantly increased among nonprone sleepers during the first 6 months of life. These reassuring results may contribute to increased use of the supine position for infant sleeping. JF - Archives of pediatrics & adolescent medicine AU - Hunt, Carl E AU - Lesko, Samuel M AU - Vezina, Richard M AU - McCoy, Rosha AU - Corwin, Michael J AU - Mandell, Frederick AU - Willinger, Marian AU - Hoffman, Howard J AU - Mitchell, Allen A AD - Department of Pediatrics, Medical College of Ohio, Toledo, USA. huntc@nhlbi.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 469 EP - 474 VL - 157 IS - 5 SN - 1072-4710, 1072-4710 KW - Tobacco Smoke Pollution KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Health Status KW - Infant KW - Prospective Studies KW - Ethnic Groups KW - Maternal Age KW - Adult KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Prevalence KW - Prone Position KW - Sudden Infant Death -- epidemiology KW - Sleep KW - Sudden Infant Death -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73297953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pediatrics+%26+adolescent+medicine&rft.atitle=Infant+sleep+position+and+associated+health+outcomes.&rft.au=Hunt%2C+Carl+E%3BLesko%2C+Samuel+M%3BVezina%2C+Richard+M%3BMcCoy%2C+Rosha%3BCorwin%2C+Michael+J%3BMandell%2C+Frederick%3BWillinger%2C+Marian%3BHoffman%2C+Howard+J%3BMitchell%2C+Allen+A&rft.aulast=Hunt&rft.aufirst=Carl&rft.date=2003-05-01&rft.volume=157&rft.issue=5&rft.spage=469&rft.isbn=&rft.btitle=&rft.title=Archives+of+pediatrics+%26+adolescent+medicine&rft.issn=10724710&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-29 N1 - Date created - 2003-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serotonin transporter gene variation is associated with alcohol sensitivity in rhesus macaques exposed to early-life stress. AN - 73292047; 12766626 AB - Decreased sensitivity to alcohol has been demonstrated to be a predictor of alcoholism in humans, and variation in the gene-linked polymorphic region of the serotonin transporter (5-HTTLPR) is associated with the response to the motor-impairing effects of alcohol. In a nonhuman primate model of excessive alcohol intake, we have shown that decreased serotonin turnover is associated with both lower initial sensitivity to alcohol and higher prospective alcohol consumption using rhesus macaques. In addition, we have demonstrated that macaques separated from their mothers and reared in peer-only groups are more likely to consume alcohol as adults. To examine the relationship between serotonin transporter genotype, early rearing experience, and initial sensitivity to alcohol, peer- and mother-reared, adolescent, alcohol-naive rhesus macaques (n = 123) were rated for intoxication after intravenous administration of ethanol (2.2 g/kg and 2.0 g/kg for males and females, respectively) during two testing periods. Serotonin transporter (rh5-HTTLPR) genotype was determined using polymerase chain reaction followed by gel electrophoresis, and data were analyzed using ANOVA and the Mann-Whitney U test. Our analyses demonstrate an effect of serotonin transporter gene variation on ethanol sensitivity, such that animals homozygous for the l allele exhibited decreased sensitivity to the ataxic and sedating effects of alcohol. This effect remained after correction for blood ethanol concentrations and birth cohort. When animals were segregated according to rearing condition, serotonin transporter gene variation predicted intoxication scores among peer-reared animals. As in some human reports, this study demonstrates a diminution in the response to alcohol in animals homozygous for the l rh5-HTTLPR allele. The phenotypic expression of this genotype in l/s animals, however, is environmentally dependent. JF - Alcoholism, clinical and experimental research AU - Barr, Christina S AU - Newman, Timothy K AU - Becker, Michelle L AU - Champoux, Maribeth AU - Lesch, Klaus Peter AU - Suomi, Stephen J AU - Goldman, David AU - Higley, J Dee AD - Labortatory of Clinical Studies, Primate Unit, National Institute on Alcohol Abuse and Alcoholism, NIH Animal Center, PO Box 529, Building 112, Poolesville, MD 20837, USA. cbarr@mail.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 812 EP - 817 VL - 27 IS - 5 SN - 0145-6008, 0145-6008 KW - Carrier Proteins KW - 0 KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Serotonin Plasma Membrane Transport Proteins KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Genotype KW - Animals KW - Dose-Response Relationship, Drug KW - Kinetics KW - Macaca mulatta KW - Male KW - Female KW - Genetic Variation KW - Ethanol -- blood KW - Carrier Proteins -- genetics KW - Ethanol -- administration & dosage KW - Alcoholic Intoxication -- genetics KW - Stress, Physiological KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73292047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serotonin+transporter+gene+variation+is+associated+with+alcohol+sensitivity+in+rhesus+macaques+exposed+to+early-life+stress.&rft.au=Barr%2C+Christina+S%3BNewman%2C+Timothy+K%3BBecker%2C+Michelle+L%3BChampoux%2C+Maribeth%3BLesch%2C+Klaus+Peter%3BSuomi%2C+Stephen+J%3BGoldman%2C+David%3BHigley%2C+J+Dee&rft.aulast=Barr&rft.aufirst=Christina&rft.date=2003-05-01&rft.volume=27&rft.issue=5&rft.spage=812&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 - 2003-08-29 N1 - Date created - 2003-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacogenetics of irinotecan. AN - 73289249; 12769780 AB - Pharmacogenetics focuses on intersubjects variation in therapeutic drug effects and toxicity depending on genetic polymorphisms. This is particularly interesting in oncology since anticancer drugs usually have a narrow margin of safety. Irinotecan [7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin] is used in cancer chemotherapy as a topoisomerase I inhibitor and it is characterised by a sometimes unpredictable severe toxicity. It is mostly intestinal with nausea, vomit and diarrhoea or haematologic with leuko-thrombocytopenia. Its complex metabolism involves many proteins. Human carboxylesterase isoforms 1 and 2 (hCE1, hCE2) activate irinotecan to its metabolite SN-38 (7-ethyl-10-hydroxycamptothecin); cytochrome P450 isoforms 3A4 and 3A5 (CYP3A4, CYP3A5) mediate the oxidation of the parental compound to irinotecan; uridino-glucuronosil transferase isoform 1A1 (UGT1A1) catalyses glucuronidation of SN-38; the multi-resistance protein isoform 2 (MRP2) allows the cellular excretion of the SN-38 glucuronide (SN-38G) and the multi-drug resistance gene (MDR1), encoding for P-glycoprotein, is responsible for the excretion of irinotecan from the cell. Polymorphic structures in the genes encoding for all these proteins have been described. In particular, the UGT1A1*28 allele has been associated with an increased toxicity after irinotecan chemotherapy. Classical parameters used in the clinic, such as body-surface area, have no longer a meaningful correlation with clinical outcome. Hence it emerges the importance of studying the individual genotype to predict the toxicity and efficacy of irinotecan and to individualise therapy. In this review, we summarise the new developments on the study of the pharmacogenetics of irinotecan, stressing its importance in drug cytotoxic effect. JF - Current medicinal chemistry. Anti-cancer agents AU - Toffoli, G AU - Cecchin, E AU - Corona, G AU - Boiocchi, M AD - Experimental and Clinical Pharmacology, Unit CRO-National Cancer Institute, 33081 Aviano-PN, Italy. gtoffoli@cro.it Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 225 EP - 237 VL - 3 IS - 3 SN - 1568-0118, 1568-0118 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Topoisomerase I Inhibitors KW - irinotecan KW - 0H43101T0J KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - UGT1A1 enzyme KW - EC 2.4.1.- KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Carboxylic Ester Hydrolases KW - EC 3.1.1.- KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Neoplasms -- drug therapy KW - Glucuronosyltransferase -- genetics KW - Neoplasms -- enzymology KW - Polymorphism, Genetic KW - Cytochrome P-450 Enzyme System -- genetics KW - Carboxylic Ester Hydrolases -- genetics KW - Humans KW - Inactivation, Metabolic -- genetics KW - Antineoplastic Agents, Phytogenic -- pharmacokinetics KW - Camptothecin -- pharmacology KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Camptothecin -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73289249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+medicinal+chemistry.+Anti-cancer+agents&rft.atitle=Pharmacogenetics+of+irinotecan.&rft.au=Toffoli%2C+G%3BCecchin%2C+E%3BCorona%2C+G%3BBoiocchi%2C+M&rft.aulast=Toffoli&rft.aufirst=G&rft.date=2003-05-01&rft.volume=3&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Current+medicinal+chemistry.+Anti-cancer+agents&rft.issn=15680118&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-11 N1 - Date created - 2003-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pulmonary toxicity during prostate cancer treatment with docetaxel and thalidomide. AN - 73289079; 12756431 AB - The standard therapies of surgery, radiotherapy, and hormonal manipulations often fail to control metastatic prostate cancer (PC). Docetaxel and thalidomide may have activity in refractory PC. We highlight the potential pulmonary toxicity when docetaxel is combined with thalidomide. We reviewed three examples of docetaxel and thalidomide pulmonary toxicity at the National Cancer Institute (NCI) and summarized the published literature regarding docetaxel and thalidomide pulmonary toxicity. Docetaxel and thalidomide pulmonary toxicity has the following four main presentations: (1). symptomatic effusions; (2). dyspnea on exertion without any objective pathologic evidence; (3). interstitial lung disease; and (4). pulmonary embolus. As chemotherapy becomes more common in the treatment of PC, clinicians must consider possible pulmonary toxicities. If pulmonary symptoms or signs develop, clinicians should consider holding chemotherapy pending a complete evaluation. JF - American journal of therapeutics AU - Behrens, Robert J AU - Gulley, James L AU - Dahut, William L AD - Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20889, USA. behrensr@mail.nih.gov PY - 2003 SP - 228 EP - 232 VL - 10 IS - 3 SN - 1075-2765, 1075-2765 KW - Angiogenesis Inhibitors KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Taxoids KW - docetaxel KW - 15H5577CQD KW - Thalidomide KW - 4Z8R6ORS6L KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Thalidomide -- adverse effects KW - Neoplasm Staging KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Risk Factors KW - Humans KW - Pulmonary Embolism -- chemically induced KW - Aged KW - Pleural Effusion -- chemically induced KW - Dyspnea -- chemically induced KW - Angiogenesis Inhibitors -- adverse effects KW - Time Factors KW - Male KW - Lung Diseases, Interstitial -- chemically induced KW - Prostatic Neoplasms -- pathology KW - Paclitaxel -- adverse effects KW - Lung Diseases -- chemically induced KW - Paclitaxel -- analogs & derivatives KW - Lung -- drug effects KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73289079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+therapeutics&rft.atitle=Pulmonary+toxicity+during+prostate+cancer+treatment+with+docetaxel+and+thalidomide.&rft.au=Behrens%2C+Robert+J%3BGulley%2C+James+L%3BDahut%2C+William+L&rft.aulast=Behrens&rft.aufirst=Robert&rft.date=2003-05-01&rft.volume=10&rft.issue=3&rft.spage=228&rft.isbn=&rft.btitle=&rft.title=American+journal+of+therapeutics&rft.issn=10752765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-10 N1 - Date created - 2003-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: activation of the mitochondria-dependent death-signaling pathway. AN - 73287349; 12771887 AB - Treating cancer cells with depsipeptide, a novel antitumor agent currently in a phase II clinical trial, causes potent upregulation of p21/WAF1 expression and cell arrest at G1 and G2 checkpoints. p21/WAF1 upregulation, however, impedes the ability of depsipeptide to induce significant apoptosis. This study was designed to determine whether flavopiridol, a synthetic cyclin-dependent kinase inhibitor known to inhibit p21 expression in tumor cells, could enhance depsipeptide-mediated apoptosis in cultured lung and esophageal cancer cells. Lung or esophageal cancer cells were exposed to depsipeptide, flavopiridol, or a combination of depsipeptide and flavopiridol. Cytotoxicity and apoptosis were quantitated by means of (4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-based assays, respectively. Cytosolic cytochrome c levels, caspase 9 activity, mitochondrial membrane depolarization, and dependence of apoptosis on caspase 9 in treated cells were studied to determine the role of the mitochondria in mediating apoptosis induced by this drug combination. Flavopiridol completely abolished depsipeptide-mediated dose-dependent upregulation of p21/WAF1 expression. Combining flavopiridol with depsipeptide resulted in a 3- to 8-fold reduction of depsipeptide inhibitory concentration of 50% values that was closely paralleled by synergistic enhancement of apoptosis (4- to 10-fold higher than levels of cell death induced by either drug alone) in all cancer cell lines. The essential role of mitochondria in mediating cell death was indicated by robust translocation of cytochrome c from the mitochondria into the cytosol, 2.5- to 5-fold activation of caspase 9, severe disruption of mitochondrial inner membrane potential, and complete inhibition of apoptosis by the selective caspase 9 inhibitor. More important, this drug combination was not toxic to primary normal epithelial cells derived from the airway or skin. The depsipeptide plus flavopiridol combination exhibits powerful and selective cytocidal activity against cancer but not normal cells. Apoptosis induced by this combination is mediated by the mitochondria-dependent death pathway. JF - The Journal of thoracic and cardiovascular surgery AU - Nguyen, Dao M AU - Schrump, William D AU - Tsai, Wilson S AU - Chen, Aaron AU - Stewart, John H AU - Steiner, Federico AU - Schrump, David S AD - Section of Thoracic Oncology, Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Dao_Nguyen@nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 1132 EP - 1142 VL - 125 IS - 5 SN - 0022-5223, 0022-5223 KW - Antineoplastic Agents KW - 0 KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Depsipeptides KW - Enzyme Inhibitors KW - Flavonoids KW - Peptides, Cyclic KW - Piperidines KW - alvocidib KW - 45AD6X575G KW - romidepsin KW - CX3T89XQBK KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Abridged Index Medicus KW - Index Medicus KW - Enzyme Inhibitors -- therapeutic use KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Mitochondria -- drug effects KW - Apoptosis -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Drug Synergism KW - Cyclins -- drug effects KW - Lung Neoplasms -- drug therapy KW - Carcinoma, Non-Small-Cell Lung -- pathology KW - Esophageal Neoplasms -- pathology KW - Flavonoids -- therapeutic use KW - Piperidines -- pharmacology KW - Piperidines -- therapeutic use KW - Peptides, Cyclic -- therapeutic use KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Flavonoids -- pharmacology KW - Peptides, Cyclic -- pharmacology KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- pharmacology KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Lung Neoplasms -- pathology KW - Esophageal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73287349?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+thoracic+and+cardiovascular+surgery&rft.atitle=Enhancement+of+depsipeptide-mediated+apoptosis+of+lung+or+esophageal+cancer+cells+by+flavopiridol%3A+activation+of+the+mitochondria-dependent+death-signaling+pathway.&rft.au=Nguyen%2C+Dao+M%3BSchrump%2C+William+D%3BTsai%2C+Wilson+S%3BChen%2C+Aaron%3BStewart%2C+John+H%3BSteiner%2C+Federico%3BSchrump%2C+David+S&rft.aulast=Nguyen&rft.aufirst=Dao&rft.date=2003-05-01&rft.volume=125&rft.issue=5&rft.spage=1132&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+thoracic+and+cardiovascular+surgery&rft.issn=00225223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-05 N1 - Date created - 2003-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A triad of costimulatory molecules synergize to amplify T-cell activation in both vector-based and vector-infected dendritic cell vaccines. AN - 73284973; 12751840 AB - The activation of a T cell has been shown to require two signals via molecules present on professional antigen presenting cells: signal 1, via a peptide/MHC complex, and signal 2, via a costimulatory molecule. Here, the role of three costimulatory molecules in the activation of T cells was examined. Poxvirus (vaccinia and avipox) vectors were employed because of their ability to efficiently express multiple genes. Murine cells provided with signal 1 and infected with either recombinant vaccinia or avipox vectors containing a TRIad of COstimulatory Molecules (B7-1/ICAM-1/LFA-3, designated TRICOM) induced the activation of T cells to a far greater extent than cells infected with vectors expressing any one or two costimulatory molecules. Despite this T-cell "hyperstimulation" using TRICOM vectors, no evidence of apoptosis above that seen using the B7-1 vector was observed. Results employing the TRICOM vectors were most dramatic under conditions of either low levels of first signal or low stimulator cell to T-cell ratios. Experiments employing a four-gene construct also showed that TRICOM recombinants could enhance antigen-specific T-cell responses in vivo. These studies thus demonstrate the ability of vectors to introduce three costimulatory molecules into cells, thereby activating both CD4+ and CD8+ T-cell populations to levels greater than those achieved with the use of only one or two costimulatory molecules. This new threshold of T-cell activation has broad implications in vaccine design and development. Dendritic cells infected with TRICOM vectors were found to greatly enhance naïve T-cell activation, and peptide-specific T-cell stimulation. In vivo, peptide-pulsed DCs infected with TRICOM vectors induced cytotoxic T lymphocyte activity markedly and significantly greater than peptide-pulsed DCs. JF - Artificial cells, blood substitutes, and immobilization biotechnology AU - Schlom, J AU - Sabzevari, H AU - Grosenbach, D W AU - Hodge, J W AD - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. js141c@nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 193 EP - 228 VL - 31 IS - 2 SN - 1073-1199, 1073-1199 KW - Antigens, CD58 KW - 0 KW - Antigens, CD80 KW - Cytokines KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Index Medicus KW - Intercellular Adhesion Molecule-1 -- immunology KW - Genetic Vectors -- administration & dosage KW - Animals KW - Cytokines -- biosynthesis KW - Antigens, CD80 -- genetics KW - CD4-Positive T-Lymphocytes -- immunology KW - Mice KW - Intercellular Adhesion Molecule-1 -- genetics KW - Antigen Presentation -- immunology KW - Antigens, CD58 -- immunology KW - Antigens, CD80 -- administration & dosage KW - Antigens, CD80 -- immunology KW - Antigens, CD58 -- genetics KW - CD8-Positive T-Lymphocytes -- immunology KW - Apoptosis -- drug effects KW - Antigens, CD58 -- administration & dosage KW - Poxviridae -- genetics KW - Genetic Vectors -- genetics KW - Intercellular Adhesion Molecule-1 -- administration & dosage KW - Drug Synergism KW - Cell Line KW - Lymphocyte Activation -- drug effects KW - Dendritic Cells -- immunology KW - Adoptive Transfer KW - Dendritic Cells -- metabolism KW - Signal Transduction -- drug effects KW - Genetic Therapy -- methods KW - Dendritic Cells -- transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73284973?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Artificial+cells%2C+blood+substitutes%2C+and+immobilization+biotechnology&rft.atitle=A+triad+of+costimulatory+molecules+synergize+to+amplify+T-cell+activation+in+both+vector-based+and+vector-infected+dendritic+cell+vaccines.&rft.au=Schlom%2C+J%3BSabzevari%2C+H%3BGrosenbach%2C+D+W%3BHodge%2C+J+W&rft.aulast=Schlom&rft.aufirst=J&rft.date=2003-05-01&rft.volume=31&rft.issue=2&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Artificial+cells%2C+blood+substitutes%2C+and+immobilization+biotechnology&rft.issn=10731199&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-27 N1 - Date created - 2003-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vaccine therapy of established tumors in the absence of autoimmunity. AN - 73270466; 12738742 AB - Many current clinical trials involve vaccination of patients with vaccines directed against tumor-associated antigens, which are, in actuality, "self-antigens" overexpressed in tumors as compared with normal tissues. As tumor vaccines become more potent through the addition of costimulatory molecules and cytokines and the use of diversified prime and boost regimes, the level of concern rises regarding the balance between antitumor immunity and pathological autoimmunity. Studies were conducted using mice bearing a transgenic self-antigen [human carcinoembryonic antigen (CEA)], which is expressed in some normal adult tissues, and tumor expressing the same self-antigen. These mice were vaccinated with recombinant poxviral vectors [recombinant vaccinia, recombinant fowlpox (rF)] encoding the CEA transgene as well as a triad of costimulatory molecules [B7-1, ICAM-1, and LFA-3 (TRICOM)]. Here we investigate the mechanism of tumor therapy and evaluate the safety of such a regimen in a self-antigen system. To our knowledge, the study reported here is the first description of a vaccine to a defined antigen where the regimen is potent enough to induce tumor therapy in the absence of autoimmunity. CEA transgenic mice were transplanted with CEA-expressing tumors. Fourteen days later, mice were vaccinated with recombinant vaccinia-CEA/TRICOM admixed with recombinant murine granulocyte macrophage colony-stimulating factor and then given low-dose interleukin 2. Mice were boosted on days 21, 28, and 35 with rF-CEA/TRICOM admixed with rF-granulocyte macrophage colony-stimulating factor and then given low-dose interleukin 2. Mice were monitored for survival and compared with groups of mice vaccinated in a similar manner with poxviral vectors containing CEA/B7-1 or CEA transgenes. To determine the mechanism of antitumor therapy, mice were depleted of T-cell subpopulations before vaccination with the CEA/TRICOM regimen. Mice successfully cured of tumor and age-matched control mice were monitored for 1 year. At 1 year, several clinical assays were carried out involving analysis of 9 serological parameters, 11 urinalysis parameters, and 14 immunological parameters. In addition, histopathology was performed on 42 tissues/mouse. The CEA/TRICOM vaccination regimen induced a therapeutic antitumor response as measured by increased survival, which was due largely to induced T-cell responses (both CD4(+) and CD8(+)) as determined by selective T-cell subset depletion. The CEA/TRICOM vaccination regimen induced a significant increase in proliferation of CD4(+) T cells to CEA protein and a significant increase in secretion of IFN-gamma from CD8(+) T cells in response to a defined CEA epitope. Despite CEA expression in normal adult gastrointestinal tissues, no toxicity was observed in the CEA/TRICOM-vaccinated group when an array of clinical serum and urine chemistry assays was conducted 1 year after vaccination. Moreover, a comprehensive histopathological evaluation of all tissues from these groups also showed no evidence of toxicity. Activation of T cells directed against a tumor-associated self-antigen, sufficient to mediate therapeutic antitumor immunity, was observed in vivo without the development of autoimmunity as analyzed by a comprehensive evaluation of biochemical, immunological, and histopathological criteria. These studies demonstrate that the use of vectors containing as many as three costimulatory molecules does not induce autoimmunity or other pathology. These studies thus demonstrate that a balance can indeed be achieved between the induction of an immune response to a self-antigen, which is capable of antitumor therapy, and the absence of autoimmunity. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Hodge, James W AU - Grosenbach, Douglas W AU - Aarts, Wilhelmina M AU - Poole, Diane J AU - Schlom, Jeffrey AD - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1750, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 1837 EP - 1849 VL - 9 IS - 5 SN - 1078-0432, 1078-0432 KW - Antigens, CD58 KW - 0 KW - Antigens, CD80 KW - Cancer Vaccines KW - Carcinoembryonic Antigen KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Index Medicus KW - Intercellular Adhesion Molecule-1 -- immunology KW - Pancreatic Neoplasms -- secondary KW - Animals KW - Vaccinia virus -- immunology KW - Humans KW - Antigens, CD80 -- genetics KW - Adenocarcinoma -- immunology KW - Adenocarcinoma -- genetics KW - Intercellular Adhesion Molecule-1 -- genetics KW - Mice, Transgenic KW - Autoimmunity -- immunology KW - Antigens, CD80 -- immunology KW - Cell Division KW - Vaccinia virus -- genetics KW - Colonic Neoplasms -- genetics KW - Adenocarcinoma -- therapy KW - Mice KW - Colonic Neoplasms -- immunology KW - Vaccination KW - Antigens, CD58 -- immunology KW - Antigens, CD58 -- genetics KW - Pancreatic Neoplasms -- therapy KW - Survival Rate KW - Colonic Neoplasms -- therapy KW - Lymphocyte Depletion KW - Mice, Inbred C57BL KW - Poxviridae -- genetics KW - Poxviridae -- immunology KW - Pancreatic Neoplasms -- immunology KW - Intestinal Neoplasms -- pathology KW - Carcinoembryonic Antigen -- immunology KW - Neoplasms, Experimental -- therapy KW - Cancer Vaccines -- therapeutic use KW - Intestinal Neoplasms -- prevention & control KW - Cancer Vaccines -- immunology KW - Neoplasms, Experimental -- immunology KW - Cancer Vaccines -- genetics KW - Genetic Vectors -- therapeutic use KW - Intestinal Neoplasms -- genetics KW - Intestinal Neoplasms -- immunology KW - T-Lymphocytes -- immunology KW - Carcinoembryonic Antigen -- genetics KW - Neoplasms, Experimental -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73270466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vaccine+therapy+of+established+tumors+in+the+absence+of+autoimmunity.&rft.au=Hodge%2C+James+W%3BGrosenbach%2C+Douglas+W%3BAarts%2C+Wilhelmina+M%3BPoole%2C+Diane+J%3BSchlom%2C+Jeffrey&rft.aulast=Hodge&rft.aufirst=James&rft.date=2003-05-01&rft.volume=9&rft.issue=5&rft.spage=1837&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 - 2004-01-12 N1 - Date created - 2003-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene selection and clustering for time-course and dose-response microarray experiments using order-restricted inference. AN - 73265246; 12724293 AB - We propose an algorithm for selecting and clustering genes according to their time-course or dose-response profiles using gene expression data. The proposed algorithm is based on the order-restricted inference methodology developed in statistics. We describe the methodology for time-course experiments although it is applicable to any ordered set of treatments. Candidate temporal profiles are defined in terms of inequalities among mean expression levels at the time points. The proposed algorithm selects genes when they meet a bootstrap-based criterion for statistical significance and assigns each selected gene to the best fitting candidate profile. We illustrate the methodology using data from a cDNA microarray experiment in which a breast cancer cell line was stimulated with estrogen for different time intervals. In this example, our method was able to identify several biologically interesting genes that previous analyses failed to reveal. JF - Bioinformatics (Oxford, England) AU - Peddada, Shyamal D AU - Lobenhofer, Edward K AU - Li, Leping AU - Afshari, Cynthia A AU - Weinberg, Clarice R AU - Umbach, David M AD - Biostatistics Branch, Laboratory of Molecular Carcinogenesis, Research Triangle Park, NC 27709, USA. peddada@embryo.niehs.nih.gov Y1 - 2003/05/01/ PY - 2003 DA - 2003 May 01 SP - 834 EP - 841 VL - 19 IS - 7 SN - 1367-4803, 1367-4803 KW - Neoplasm Proteins KW - 0 KW - Estradiol KW - 4TI98Z838E KW - Index Medicus KW - Sequence Analysis, DNA -- methods KW - Computer Simulation KW - Models, Genetic KW - Humans KW - Neoplasm Proteins -- genetics KW - Estradiol -- pharmacology KW - Transcription, Genetic -- genetics KW - Cell Line, Tumor KW - Statistics as Topic KW - Time Factors KW - Sequence Alignment -- methods KW - Neoplasm Proteins -- metabolism KW - Breast Neoplasms -- genetics KW - Dose-Response Relationship, Drug KW - Oligonucleotide Array Sequence Analysis -- methods KW - Algorithms KW - Breast Neoplasms -- metabolism KW - Cluster Analysis KW - Gene Expression Profiling -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73265246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioinformatics+%28Oxford%2C+England%29&rft.atitle=Gene+selection+and+clustering+for+time-course+and+dose-response+microarray+experiments+using+order-restricted+inference.&rft.au=Peddada%2C+Shyamal+D%3BLobenhofer%2C+Edward+K%3BLi%2C+Leping%3BAfshari%2C+Cynthia+A%3BWeinberg%2C+Clarice+R%3BUmbach%2C+David+M&rft.aulast=Peddada&rft.aufirst=Shyamal&rft.date=2003-05-01&rft.volume=19&rft.issue=7&rft.spage=834&rft.isbn=&rft.btitle=&rft.title=Bioinformatics+%28Oxford%2C+England%29&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-29 N1 - Date created - 2003-05-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of psychiatric disorders in predicting drug dependence treatment outcomes. AN - 73263560; 12727692 AB - Previous research has demonstrated that psychiatric disorders are common among people who abuse alcohol and drugs, but few studies have examined the relationship of psychiatric disorders to drug treatment outcome. The authors conducted such an examination. They successfully reinterviewed 401 drug-dependent subjects (94% of the baseline in-treatment sample) and determined their drug abuse status at follow-up 12 months later. Analyses indicated that several baseline psychiatric disorders predicted worse outcomes at follow-up. Major depression predicted using a larger number of substances and having more drug dependence diagnoses and symptoms. Alcohol dependence predicted more dependence diagnoses, antisocial personality disorder predicted using a larger number of substances, and generalized anxiety disorder predicted having more dependence diagnoses. Outcomes among men were more closely associated with psychiatric status than outcomes among women, except for phobias, which predicted a better outcome among women. These results are unique in their assessment of individuals dependent on illicit substances. Overall, the authors found that women with phobias had better outcomes and that men with psychiatric disorders in general, men with major depression, and men with antisocial personality disorder had worse outcomes. JF - The American journal of psychiatry AU - Compton, Wilson M AU - Cottler, Linda B AU - Jacobs, Jacqueline L AU - Ben-Abdallah, Arbi AU - Spitznagel, Edward L AD - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. wcompton@nida.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 890 EP - 895 VL - 160 IS - 5 SN - 0002-953X, 0002-953X KW - Abridged Index Medicus KW - Index Medicus KW - Missouri -- epidemiology KW - Sex Factors KW - Humans KW - Phobic Disorders -- epidemiology KW - Longitudinal Studies KW - Comorbidity KW - Alcohol-Related Disorders -- diagnosis KW - Depressive Disorder -- epidemiology KW - Antisocial Personality Disorder -- epidemiology KW - Psychiatric Status Rating Scales KW - Substance Abuse Treatment Centers KW - Logistic Models KW - Risk Factors KW - Adult KW - Treatment Outcome KW - Depressive Disorder -- diagnosis KW - Antisocial Personality Disorder -- diagnosis KW - Follow-Up Studies KW - Phobic Disorders -- diagnosis KW - Male KW - Female KW - Alcohol-Related Disorders -- epidemiology KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- diagnosis KW - Mental Disorders -- diagnosis KW - Mental Disorders -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73263560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=The+role+of+psychiatric+disorders+in+predicting+drug+dependence+treatment+outcomes.&rft.au=Compton%2C+Wilson+M%3BCottler%2C+Linda+B%3BJacobs%2C+Jacqueline+L%3BBen-Abdallah%2C+Arbi%3BSpitznagel%2C+Edward+L&rft.aulast=Compton&rft.aufirst=Wilson&rft.date=2003-05-01&rft.volume=160&rft.issue=5&rft.spage=890&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-17 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of agricultural pesticides and prostate cancer risk in the Agricultural Health Study cohort. AN - 73261076; 12727674 AB - The authors examined the relation between 45 common agricultural pesticides and prostate cancer incidence in a prospective cohort study of 55,332 male pesticide applicators from Iowa and North Carolina with no prior history of prostate cancer. Data were collected by means of self-administered questionnaires completed at enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 1999. A prostate cancer standardized incidence ratio was computed for the cohort. Odds ratios were computed for individual pesticides and for pesticide use patterns identified by means of factor analysis. A prostate cancer standardized incidence ratio of 1.14 (95% confidence interval: 1.05, 1.24) was observed for the Agricultural Health Study cohort. Use of chlorinated pesticides among applicators over 50 years of age and methyl bromide use were significantly associated with prostate cancer risk. Several other pesticides showed a significantly increased risk of prostate cancer among study subjects with a family history of prostate cancer but not among those with no family history. Important family history-pesticide interactions were observed. JF - American journal of epidemiology AU - Alavanja, Michael C R AU - Samanic, Claudine AU - Dosemeci, Mustafa AU - Lubin, Jay AU - Tarone, Robert AU - Lynch, Charles F AU - Knott, Charles AU - Thomas, Kent AU - Hoppin, Jane A AU - Barker, Joseph AU - Coble, Joseph AU - Sandler, Dale P AU - Blair, Aaron AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA. alavanjm@mail.nih.gov Y1 - 2003/05/01/ PY - 2003 DA - 2003 May 01 SP - 800 EP - 814 VL - 157 IS - 9 SN - 0002-9262, 0002-9262 KW - Pesticides KW - 0 KW - Index Medicus KW - Odds Ratio KW - Humans KW - Cohort Studies KW - Adult KW - Surveys and Questionnaires KW - Incidence KW - Aged KW - Middle Aged KW - North Carolina -- epidemiology KW - Male KW - Iowa -- epidemiology KW - Age Distribution KW - Prostatic Neoplasms -- etiology KW - Prostatic Neoplasms -- epidemiology KW - Agricultural Workers' Diseases -- etiology KW - Agricultural Workers' Diseases -- epidemiology KW - Pesticides -- classification KW - Agricultural Workers' Diseases -- chemically induced KW - Prostatic Neoplasms -- chemically induced KW - Pesticides -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73261076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Use+of+agricultural+pesticides+and+prostate+cancer+risk+in+the+Agricultural+Health+Study+cohort.&rft.au=Alavanja%2C+Michael+C+R%3BSamanic%2C+Claudine%3BDosemeci%2C+Mustafa%3BLubin%2C+Jay%3BTarone%2C+Robert%3BLynch%2C+Charles+F%3BKnott%2C+Charles%3BThomas%2C+Kent%3BHoppin%2C+Jane+A%3BBarker%2C+Joseph%3BCoble%2C+Joseph%3BSandler%2C+Dale+P%3BBlair%2C+Aaron&rft.aulast=Alavanja&rft.aufirst=Michael+C&rft.date=2003-05-01&rft.volume=157&rft.issue=9&rft.spage=800&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 - 2003-07-03 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of eicosanoids and NSAIDs as PPARgamma ligands in colorectal carcinoma cells. AN - 73250628; 12711249 AB - The activation of peroxisome proliferator activated receptor gamma (PPARgamma) may play a role in the control of colorectal carcinogenesis. The expression of PPARgamma was examined by Western blotting in human colorectal tumors and matched normal adjacent tissues, as well as in various colorectal carcinoma cell lines. In the tissues, the expression of PPARgamma was elevated in tumors relative to the adjacent normal tissues. Each colorectal carcinoma cell line expressed PPARgamma. The ability of various eicosanoids to bind PPARgamma in colorectal carcinoma cells was investigated using luciferase reporter assays. The well-known PPARgamma ligands, troglitazone and 15-deoxy-Delta(12,14)-prostaglandin J(2) strongly induced PPARgamma binding activity. Products of lipoxygenases displayed moderate binding activity, while other prostaglandins and fatty acids displayed little or no reporter activation. The activation of PPARgamma by 13(S)-HODE, the major metabolite of 15-lipoxygenase-1 from linoleic acid, was concentration dependent reaching maximum at 10 micro M (35-fold activation). The endogenous production of 13(S)-HODE by expression of 15-LO-1 did not activate PPARgamma. The ability of various nonsteroidal anti-inflammatory drugs (NSAIDs) to induce PPARgamma activation was also evaluated. The conventional NSAIDs that inhibit both cyclooxygenases (COX-1 and COX-2) also induced PPARgamma binding activity. In general, however, neither COX-1- nor COX-2-specific inhibitors induced the activation of PPARgamma. Taken together, the metabolites of 15-lipoxygenase and the conventional NSAIDs were confirmed as exogenous ligands for PPARgamma in colorectal carcinoma cells. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Nixon, J B AU - Kamitani, H AU - Baek, S J AU - Eling, T E AD - Eicosanoid Biochemistry Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 323 EP - 330 VL - 68 IS - 5 SN - 0952-3278, 0952-3278 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Eicosanoids KW - Ligands KW - Linoleic Acids KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - 13-hydroxy-9,11-octadecadienoic acid KW - 5204-88-6 KW - Linoleic Acid KW - 9KJL21T0QJ KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Linoleic Acid -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Luciferases -- metabolism KW - Caco-2 Cells KW - Cell Line, Tumor KW - Protein Binding KW - Chromatography, High Pressure Liquid KW - Blotting, Western KW - Linoleic Acids -- pharmacology KW - Linoleic Acids -- metabolism KW - Linoleic Acid -- pharmacology KW - Genetic Vectors -- genetics KW - Luciferases -- genetics KW - Anti-Inflammatory Agents, Non-Steroidal -- metabolism KW - Transcription Factors -- metabolism KW - Colorectal Neoplasms -- pathology KW - Colorectal Neoplasms -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Eicosanoids -- pharmacology KW - Eicosanoids -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Transcription Factors -- genetics KW - Colorectal Neoplasms -- drug therapy KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73250628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=Evaluation+of+eicosanoids+and+NSAIDs+as+PPARgamma+ligands+in+colorectal+carcinoma+cells.&rft.au=Nixon%2C+J+B%3BKamitani%2C+H%3BBaek%2C+S+J%3BEling%2C+T+E&rft.aulast=Nixon&rft.aufirst=J&rft.date=2003-05-01&rft.volume=68&rft.issue=5&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-16 N1 - Date created - 2003-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The frailty syndrome: a critical issue in geriatric oncology. AN - 73250477; 12711358 AB - Evidence exists that the geriatric intervention guided by Comprehensive Geriatric Assessment (CGA) has positive effects on a number of important health outcomes in frail older patients. Although a number of observational studies, editorials, special articles and clinical reports, suggest that CGA should be used to guide the assessment and clinical decision-making in older cancer patients, there is limited support to this view in the literature. Older patients that are diagnosed with cancer are usually healthier and less problematic than persons of the same age who are randomly sampled from the general population. In these persons, the cancer dominates the clinical picture and, therefore, instruments especially tuned for the frail elderly may provide little information. The concept of the frailty syndrome, characterized by high susceptibility, low functional reserve and unstable homeostasis, has recently received a lot of attention by the geriatric community. A CGA approach, which also evaluates elements of the frailty syndrome, may be of great interest for those oncologists who want to identify older patients likely to develop severe toxicity and severe side effects in response to aggressive treatment. Improvements in the definition of the frailty syndrome may profit from the clinical experience of oncologists. JF - Critical reviews in oncology/hematology AU - Ferrucci, Luigi AU - Guralnik, Jack M AU - Cavazzini, Chiara AU - Bandinelli, Stefania AU - Lauretani, Fulvio AU - Bartali, Benedetta AU - Repetto, Lazzaro AU - Longo, Dan L AD - Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. ferrucci@dada.it Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 127 EP - 137 VL - 46 IS - 2 SN - 1040-8428, 1040-8428 KW - Index Medicus KW - Geriatrics -- methods KW - Disease Susceptibility KW - Medical Oncology -- methods KW - Syndrome KW - Humans KW - Aged KW - Adaptation, Physiological KW - Homeostasis KW - Health Services for the Aged KW - Frail Elderly KW - Neoplasms -- epidemiology KW - Patient Care Planning KW - Neoplasms -- therapy KW - Geriatric Assessment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73250477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+reviews+in+oncology%2Fhematology&rft.atitle=The+frailty+syndrome%3A+a+critical+issue+in+geriatric+oncology.&rft.au=Ferrucci%2C+Luigi%3BGuralnik%2C+Jack+M%3BCavazzini%2C+Chiara%3BBandinelli%2C+Stefania%3BLauretani%2C+Fulvio%3BBartali%2C+Benedetta%3BRepetto%2C+Lazzaro%3BLongo%2C+Dan+L&rft.aulast=Ferrucci&rft.aufirst=Luigi&rft.date=2003-05-01&rft.volume=46&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Critical+reviews+in+oncology%2Fhematology&rft.issn=10408428&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-23 N1 - Date created - 2003-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms. AN - 73245477; 12738056 AB - Methylenedioxymethamphetamine (MDMA, Ecstasy) is a very popular drug of abuse. This has led to new intense concerns relevant to its nefarious neuropsychiatric effects. These adverse events might be related to the neurotoxic effects of the drug. Although the mechanisms of MDMA-induced neurotoxicity remain to be fully characterized, exposure to the drug can cause acute and long-term neurotoxic effects in animals and nonhuman primates. Recent studies have also documented possible toxic effects in the developing fetus. Nevertheless, there is still much debate concerning the effects of the drug in humans and how to best extrapolate animal and nonhuman primate data to the human condition. Herein, we review the evidence documenting the adverse effects of the drug in some animal models. We also discuss possible mechanisms for the development of MDMA neurotoxicity. Data supporting deleterious effects of this drug on the developing fetus are also described. Much remains to be done in order to clarify the molecular and biochemical pathways involved in the long-term neuroplastic changes associated with MDMA abuse. JF - Brain research. Brain research reviews AU - Lyles, Johnalyn AU - Cadet, Jean Lud AD - Molecular Neuropsychiatry Branch, National Institutes of Health/National Institute on Drug Abuse Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 155 EP - 168 VL - 42 IS - 2 KW - Hallucinogens KW - 0 KW - Neurotransmitter Agents KW - Receptors, Serotonin KW - Nitric Oxide KW - 31C4KY9ESH KW - N-Methyl-3,4-methylenedioxyamphetamine KW - KE1SEN21RM KW - Index Medicus KW - Receptors, Serotonin -- drug effects KW - Models, Animal KW - Animals KW - Neurotransmitter Agents -- metabolism KW - Humans KW - Brain -- drug effects KW - Nitric Oxide -- metabolism KW - Brain -- metabolism KW - Receptors, Serotonin -- metabolism KW - Embryonic and Fetal Development -- drug effects KW - N-Methyl-3,4-methylenedioxyamphetamine -- metabolism KW - Neurotoxicity Syndromes -- etiology KW - N-Methyl-3,4-methylenedioxyamphetamine -- toxicity KW - N-Methyl-3,4-methylenedioxyamphetamine -- analogs & derivatives KW - Hallucinogens -- toxicity KW - Hallucinogens -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73245477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Methylenedioxymethamphetamine+%28MDMA%2C+Ecstasy%29+neurotoxicity%3A+cellular+and+molecular+mechanisms.&rft.au=Lyles%2C+Johnalyn%3BCadet%2C+Jean+Lud&rft.aulast=Lyles&rft.aufirst=Johnalyn&rft.date=2003-05-01&rft.volume=42&rft.issue=2&rft.spage=155&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 - 2003-07-11 N1 - Date created - 2003-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutations in the tumor-associated cytokine, autotaxin, eliminate nucleotide phosphodiesterase, lysophospholipase D, and motogenic activities. AN - 73241406; 12727817 AB - The exo-enzyme autotaxin/NPP2 (ATX/NPP2) is a potent stimulator of cell migration, invasion, metastasis, and angiogenesis. Recently, ATX/NPP2 was found to possess lysophospholipase D (lyso-LPD) activity, generating the bioactive mediator lysophosphatidic acid from precursors. In the present study, we used site-directed mutagenesis to delineate the active domain of lysophospholipid catalytic activity and to examine potential overlap with the nucleotide phosphodiesterase domain. We found four amino acid residues obligatory for the phosphodiesterase, lyso-PLD, and migration-stimulating activities of ATX/NPP2, suggesting that 5'-nucleotide phosphodiesterase (PDE) and lyso-PLD share a common reaction mechanism and inviting design of enzymatic inhibitors as therapeutic agents for neoplastic disease. JF - Cancer research AU - Koh, Eunjin AU - Clair, Timothy AU - Woodhouse, Elisa C AU - Schiffmann, Elliott AU - Liotta, Lance AU - Stracke, Mary AD - Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. kohe@mail.nih.gov Y1 - 2003/05/01/ PY - 2003 DA - 2003 May 01 SP - 2042 EP - 2045 VL - 63 IS - 9 SN - 0008-5472, 0008-5472 KW - Glycoproteins KW - 0 KW - Multienzyme Complexes KW - Receptors, Purinergic P1 KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - Phosphodiesterase I KW - EC 3.1.4.1 KW - alkylglycerophosphoethanolamine phosphodiesterase KW - EC 3.1.4.39 KW - Pyrophosphatases KW - EC 3.6.1.- KW - Glucose-6-Phosphate Isomerase KW - EC 5.3.1.9 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Receptors, Purinergic P1 -- physiology KW - COS Cells KW - Humans KW - Cercopithecus aethiops KW - Cell Movement -- genetics KW - Protein Structure, Tertiary KW - Structure-Activity Relationship KW - Phosphoric Diester Hydrolases -- genetics KW - Glucose-6-Phosphate Isomerase -- metabolism KW - Glycoproteins -- metabolism KW - Point Mutation KW - Phosphoric Diester Hydrolases -- metabolism KW - Glycoproteins -- genetics KW - Glucose-6-Phosphate Isomerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73241406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Site-directed+mutations+in+the+tumor-associated+cytokine%2C+autotaxin%2C+eliminate+nucleotide+phosphodiesterase%2C+lysophospholipase+D%2C+and+motogenic+activities.&rft.au=Koh%2C+Eunjin%3BClair%2C+Timothy%3BWoodhouse%2C+Elisa+C%3BSchiffmann%2C+Elliott%3BLiotta%2C+Lance%3BStracke%2C+Mary&rft.aulast=Koh&rft.aufirst=Eunjin&rft.date=2003-05-01&rft.volume=63&rft.issue=9&rft.spage=2042&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 - 2003-06-16 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brain hyperthermia is induced by methamphetamine and exacerbated by social interaction. AN - 73241332; 12736362 AB - Hyperthermia is a symptom of methamphetamine (METH) intoxication and a factor implicated in neurotoxicity during chronic METH use. To characterize the thermic response to METH, it was injected once daily into rats at increasing doses (0, 1, 3, and 9 mg/kg, s.c.) while brain [nucleus accumbens (NAcc), hippocampus] and body (deep temporal muscle) temperatures were continuously monitored. METH produced dose-dependent hyperthermia, with brain structures (especially the NAcc) showing a more rapid and pronounced temperature increase than the muscle. At the highest dose, brain and body temperatures increased 3.5-4.0 degrees C above basal levels and remained elevated for 3-5 hr. Stressful and other high-activity situations such as interaction with a conspecific female are also known to induce a significant hyperthermic response in the rat. A combination of social interaction and METH administration was tested for additive effects. Male rats were exposed daily to a conspecific female for a total of 120 min, and METH was injected at the same doses 30 min after the initial contact with the female. An initial hyperthermic response ( approximately 1.5 degrees C) to social interaction was followed by a large and prolonged hyperthermic response (3.5-5.0 degrees C, 5-7 hr at 9 mg/kg) to METH, which was again stronger in brain structures (especially in the NAcc) than in the muscle. Although the combined effect of the hyperthermic events was not additive, METH administration during social interaction produced stronger and longer-lasting increases in brain and body temperature than that induced by drug alone, heating the brain in some animals near its biological limit (>41 degrees C). JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Brown, P Leon AU - Wise, Roy A AU - Kiyatkin, Eugene A AD - Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 2003/05/01/ PY - 2003 DA - 2003 May 01 SP - 3924 EP - 3929 VL - 23 IS - 9 KW - Central Nervous System Stimulants KW - 0 KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Rats, Long-Evans KW - Body Temperature -- drug effects KW - Nucleus Accumbens -- drug effects KW - Dose-Response Relationship, Drug KW - Muscle, Skeletal -- physiopathology KW - Nucleus Accumbens -- physiopathology KW - Muscle, Skeletal -- drug effects KW - Amphetamine-Related Disorders -- physiopathology KW - Hippocampus -- drug effects KW - Rats KW - Behavior, Animal -- drug effects KW - Hippocampus -- physiopathology KW - Female KW - Male KW - Fever -- chemically induced KW - Brain -- physiopathology KW - Brain -- drug effects KW - Interpersonal Relations KW - Fever -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73241332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Brain+hyperthermia+is+induced+by+methamphetamine+and+exacerbated+by+social+interaction.&rft.au=Brown%2C+P+Leon%3BWise%2C+Roy+A%3BKiyatkin%2C+Eugene+A&rft.aulast=Brown&rft.aufirst=P&rft.date=2003-05-01&rft.volume=23&rft.issue=9&rft.spage=3924&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-19 N1 - Date created - 2003-05-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. AN - 73236816; 12704387 AB - To gain insight into melanoma pathogenesis, we characterized an insertional mouse mutant, TG3, that is predisposed to develop multiple melanomas. Physical mapping identified multiple tandem insertions of the transgene into intron 3 of Grm1 (encoding metabotropic glutamate receptor 1) with concomitant deletion of 70 kb of intronic sequence. To assess whether this insertional mutagenesis event results in alteration of transcriptional regulation, we analyzed Grm1 and two flanking genes for aberrant expression in melanomas from TG3 mice. We observed aberrant expression of only Grm1. Although we did not detect its expression in normal mouse melanocytes, Grm1 was ectopically expressed in the melanomas from TG3 mice. To confirm the involvement of Grm1 in melanocytic neoplasia, we created an additional transgenic line with Grm1 expression driven by the dopachrome tautomerase promoter. Similar to the original TG3, the Tg(Grm1)EPv line was susceptible to melanoma. In contrast to human melanoma, these transgenic mice had a generalized hyperproliferation of melanocytes with limited transformation to fully malignant metastasis. We detected expression of GRM1 in a number of human melanoma biopsies and cell lines but not in benign nevi and melanocytes. This study provides compelling evidence for the importance of metabotropic glutamate signaling in melanocytic neoplasia. JF - Nature genetics AU - Pollock, Pamela M AU - Cohen-Solal, Karine AU - Sood, Raman AU - Namkoong, Jin AU - Martino, Jeffrey J AU - Koganti, Aruna AU - Zhu, Hua AU - Robbins, Christiane AU - Makalowska, Izabela AU - Shin, Seung-Shick AU - Marin, Yari AU - Roberts, Kathleen G AU - Yudt, Laura M AU - Chen, Amy AU - Cheng, Jun AU - Incao, Arturo AU - Pinkett, Heather W AU - Graham, Christopher L AU - Dunn, Karen AU - Crespo-Carbone, Steven M AU - Mackason, Kerine R AU - Ryan, Kevin B AU - Sinsimer, Daniel AU - Goydos, James AU - Reuhl, Kenneth R AU - Eckhaus, Michael AU - Meltzer, Paul S AU - Pavan, William J AU - Trent, Jeffrey M AU - Chen, Suzie AD - Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 108 EP - 112 VL - 34 IS - 1 SN - 1061-4036, 1061-4036 KW - DNA, Complementary KW - 0 KW - DNA, Neoplasm KW - Receptors, Metabotropic Glutamate KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - DNA, Complementary -- genetics KW - Transfection KW - Molecular Sequence Data KW - Mice, Inbred C57BL KW - DNA, Neoplasm -- genetics KW - Mice KW - Mice, Transgenic KW - Signal Transduction KW - Mutagenesis, Insertional KW - Skin Neoplasms -- genetics KW - Melanoma -- pathology KW - Melanoma -- genetics KW - Receptors, Metabotropic Glutamate -- genetics KW - Receptors, Metabotropic Glutamate -- metabolism KW - Skin Neoplasms -- pathology KW - Skin Neoplasms -- metabolism KW - Melanoma -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73236816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genetics&rft.atitle=Melanoma+mouse+model+implicates+metabotropic+glutamate+signaling+in+melanocytic+neoplasia.&rft.au=Pollock%2C+Pamela+M%3BCohen-Solal%2C+Karine%3BSood%2C+Raman%3BNamkoong%2C+Jin%3BMartino%2C+Jeffrey+J%3BKoganti%2C+Aruna%3BZhu%2C+Hua%3BRobbins%2C+Christiane%3BMakalowska%2C+Izabela%3BShin%2C+Seung-Shick%3BMarin%2C+Yari%3BRoberts%2C+Kathleen+G%3BYudt%2C+Laura+M%3BChen%2C+Amy%3BCheng%2C+Jun%3BIncao%2C+Arturo%3BPinkett%2C+Heather+W%3BGraham%2C+Christopher+L%3BDunn%2C+Karen%3BCrespo-Carbone%2C+Steven+M%3BMackason%2C+Kerine+R%3BRyan%2C+Kevin+B%3BSinsimer%2C+Daniel%3BGoydos%2C+James%3BReuhl%2C+Kenneth+R%3BEckhaus%2C+Michael%3BMeltzer%2C+Paul+S%3BPavan%2C+William+J%3BTrent%2C+Jeffrey+M%3BChen%2C+Suzie&rft.aulast=Pollock&rft.aufirst=Pamela&rft.date=2003-05-01&rft.volume=34&rft.issue=1&rft.spage=108&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-27 N1 - Date created - 2003-04-30 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AY135650; GENBANK; AF320126; AY162264; AY158230 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genome diversification in Staphylococcus aureus: Molecular evolution of a highly variable chromosomal region encoding the Staphylococcal exotoxin-like family of proteins. AN - 73232472; 12704157 AB - Recent genomic studies have revealed extensive variation in natural populations of many pathogenic bacteria. However, the evolutionary processes which contribute to much of this variation remain unclear. A previous whole-genome DNA microarray study identified variation at a large chromosomal region (RD13) of Staphylococcus aureus which encodes a family of proteins with homology to staphylococcal and streptococcal superantigens, designated staphylococcal exotoxin-like (SET) proteins. In the present study, RD13 was found in all 63 S. aureus isolates of divergent clonal, geographic, and disease origins but contained a high level of variation in gene content in different strains. A central variable region which contained from 6 to 10 different set genes, depending on the strain, was identified, and DNA sequence analysis suggests that horizontal gene transfer and recombination have contributed to the diversification of RD13. Phylogenetic analysis based on the RD13 DNA sequence of 18 strains suggested that loss of various set genes has occurred independently several times, in separate lineages of pathogenic S. aureus, providing a model to explain the molecular variation of RD13 in extant strains. In spite of multiple episodes of set deletion, analysis of the ratio of silent substitutions in set genes to amino acid replacements in their products suggests that purifying selection (selective constraint) is acting to maintain SET function. Further, concurrent transcription in vitro of six of the seven set genes in strain COL was detected, indicating that the expression of set genes has been maintained in contemporary strains, and Western immunoblot analysis indicated that multiple SET proteins are expressed during the course of human infections. Overall, we have shown that the chromosomal region RD13 has diversified extensively through episodes of gene deletion and recombination. The coexpression of many set genes and the production of multiple SET proteins during human infection suggests an important role in host-pathogen interactions. JF - Infection and immunity AU - Fitzgerald, J Ross AU - Reid, Sean D AU - Ruotsalainen, Eeva AU - Tripp, Timothy J AU - Liu, MengYao AU - Cole, Robert AU - Kuusela, Pentti AU - Schlievert, Patrick M AU - Järvinen, Asko AU - Musser, James M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 2827 EP - 2838 VL - 71 IS - 5 SN - 0019-9567, 0019-9567 KW - Exotoxins KW - 0 KW - Recombinant Proteins KW - Index Medicus KW - Phylogeny KW - Polymerase Chain Reaction KW - Animals KW - Blotting, Western KW - Base Sequence KW - Polymorphism, Restriction Fragment Length KW - Molecular Sequence Data KW - Rabbits KW - Recombinant Proteins -- analysis KW - Staphylococcal Infections -- blood KW - Exotoxins -- genetics KW - Exotoxins -- analysis KW - Genome, Bacterial KW - Staphylococcus aureus -- genetics KW - Chromosomes, Bacterial KW - Exotoxins -- toxicity KW - Evolution, Molecular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73232472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genome+diversification+in+Staphylococcus+aureus%3A+Molecular+evolution+of+a+highly+variable+chromosomal+region+encoding+the+Staphylococcal+exotoxin-like+family+of+proteins.&rft.au=Fitzgerald%2C+J+Ross%3BReid%2C+Sean+D%3BRuotsalainen%2C+Eeva%3BTripp%2C+Timothy+J%3BLiu%2C+MengYao%3BCole%2C+Robert%3BKuusela%2C+Pentti%3BSchlievert%2C+Patrick+M%3BJ%C3%A4rvinen%2C+Asko%3BMusser%2C+James+M&rft.aulast=Fitzgerald&rft.aufirst=J&rft.date=2003-05-01&rft.volume=71&rft.issue=5&rft.spage=2827&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 - 2003-05-15 N1 - Date created - 2003-04-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Clin Microbiol Rev. 2000 Jan;13(1):16-34, table of contents [10627489] Mol Biol Evol. 1986 Sep;3(5):418-26 [3444411] Trends Microbiol. 2000 Aug;8(8):369-75 [10920396] Infect Immun. 2001 Feb;69(2):822-31 [11159974] Lancet. 2001 Apr 21;357(9264):1225-40 [11418146] Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8821-6 [11447287] Bioinformatics. 2001 Dec;17(12):1244-5 [11751241] Trends Microbiol. 2001 Nov;9(11):547-53 [11825715] J Bacteriol. 2002 Mar;184(5):1430-7 [11844774] Lancet. 2002 May 25;359(9320):1819-27 [12044378] J Biol Chem. 2002 Aug 30;277(35):32274-81 [12082105] J Clin Microbiol. 1990 Sep;28(9):1903-5 [2229371] J Mol Evol. 1992 Feb;34(2):126-9 [1556748] Infect Immun. 1993 Oct;61(10):4254-62 [8406814] Nucleic Acids Res. 1994 Nov 11;22(22):4673-80 [7984417] J Bacteriol. 1999 Jan;181(1):153-60 [9864325] Trends Microbiol. 1998 Dec;6(12):484-8 [10036727] Anal Biochem. 1976 May 7;72:248-54 [942051] Infect Immun. 2000 Aug;68(8):4407-15 [10899837] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase III study of cyclophosphamide, doxorubicin, and fluorouracil (CAF) plus leucovorin versus CAF for metastatic breast cancer: Cancer and Leukemia Group B 9140. AN - 73225996; 12721259 AB - To determine whether biochemical modulation with LV (leucovorin) enhances the efficacy of CAF (cyclophosphamide, doxorubicin, and fluorouracil) against metastatic breast cancer. Women with histologically confirmed stage IV breast cancer, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, and no prior chemotherapy for metastatic disease were randomly assigned to receive CAF (cyclophosphamide 500 mg/m2 day 1, doxorubicin 40 mg/m2 day 1, and fluorouracil [FU] 200 mg/m2 intravenous bolus days 1 to 5) with or without LV (LV 200 mg/m2 over 30 minutes days 1 to 5 given 1 hour before FU). Two hundred forty-two patients were randomly assigned to treatment; 124 patients had visceral crisis and 40 patients had a CALGB performance status score of 2. The median follow-up was 6 years. The two study arms were similar with regard to serious adverse events; four patients died from treatment-related causes, two patients on each study arm. Predictive variables for time to treatment failure and survival were visceral disease and performance status. The overall response rate was 29% for CAF versus 28% for CAF plus LV. The median time to treatment failure (9 months) and median survival (1.7 years) did not differ by treatment arm. Modulation of CAF with LV improved neither response rates nor survival among women with metastatic breast cancer, compared with CAF alone. Multivariate analyses confirmed the prognostic importance of performance status and visceral crisis. However, the overall and complete response rates, response durations, time to treatment failure, and survival were the same in the two treatment arms. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Parnes, H L AU - Cirrincione, C AU - Aisner, J AU - Berry, D A AU - Allen, S L AU - Abrams, J AU - Chuang, E AU - Cooper, M R AU - Perry, M C AU - Duggan, D B AU - Szatrowski, T P AU - Henderson, I C AU - Norton, L AU - Cancer and Leukemia Group B AD - Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, 6130 Executive Plaza EPN Room 2100, Rockville MD 20852, USA. hp24c@nih.gov ; Cancer and Leukemia Group B Y1 - 2003/05/01/ PY - 2003 DA - 2003 May 01 SP - 1819 EP - 1824 VL - 21 IS - 9 SN - 0732-183X, 0732-183X KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Humans KW - Leucovorin -- administration & dosage KW - Health Status KW - Disease Progression KW - Prognosis KW - Survival KW - Aged KW - Doxorubicin -- administration & dosage KW - Viscera -- pathology KW - Fluorouracil -- administration & dosage KW - Treatment Outcome KW - Neoplasm Metastasis KW - Middle Aged KW - Female KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73225996?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Phase+III+study+of+cyclophosphamide%2C+doxorubicin%2C+and+fluorouracil+%28CAF%29+plus+leucovorin+versus+CAF+for+metastatic+breast+cancer%3A+Cancer+and+Leukemia+Group+B+9140.&rft.au=Parnes%2C+H+L%3BCirrincione%2C+C%3BAisner%2C+J%3BBerry%2C+D+A%3BAllen%2C+S+L%3BAbrams%2C+J%3BChuang%2C+E%3BCooper%2C+M+R%3BPerry%2C+M+C%3BDuggan%2C+D+B%3BSzatrowski%2C+T+P%3BHenderson%2C+I+C%3BNorton%2C+L%3BCancer+and+Leukemia+Group+B&rft.aulast=Parnes&rft.aufirst=H&rft.date=2003-05-01&rft.volume=21&rft.issue=9&rft.spage=1819&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 - 2003-05-20 N1 - Date created - 2003-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Histidine and aspartic acid residues important for immunoglobulin G endopeptidase activity of the group A Streptococcus opsonophagocytosis-inhibiting Mac protein. AN - 73223451; 12704162 AB - The secreted Mac protein made by serotype M1 group A Streptococcus (GAS) (designated Mac(5005)) inhibits opsonophagocytosis and killing of GAS by human polymorphonuclear neutrophils. This protein also has cysteine endopeptidase activity against human immunoglobulin G (IgG). Site-directed mutagenesis was used to identify histidine and aspartic acid residues important for Mac IgG endopeptidase activity. Replacement of His262 with Ala abolished Mac5005 IgG endopeptidase activity. Asp284Ala and Asp286Ala mutant proteins had compromised enzymatic activity, whereas 21 other Asp-to-Ala mutant proteins cleaved human IgG at the apparent wild-type level. The results suggest that His262 is an active-site residue and that Asp284 and Asp286 are important for the enzymatic activity or structure of Mac protein. These Mac mutants provide new information about structure-activity relationships in this protein and will assist study of the mechanism of inhibition of opsonophagocytosis and killing of GAS by Mac. JF - Infection and immunity AU - Lei, Benfang AU - Liu, Mengyao AU - Meyers, Elishia G AU - Manning, Heather M AU - Nagiec, Michael J AU - Musser, James M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 2881 EP - 2884 VL - 71 IS - 5 SN - 0019-9567, 0019-9567 KW - Bacterial Proteins KW - 0 KW - Immunoglobulin G KW - Opsonin Proteins KW - Aspartic Acid KW - 30KYC7MIAI KW - Histidine KW - 4QD397987E KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Opsonin Proteins -- physiology KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Binding Sites KW - Streptococcus pyogenes -- chemistry KW - Bacterial Proteins -- chemistry KW - Cysteine Endopeptidases -- metabolism KW - Streptococcus pyogenes -- immunology KW - Phagocytosis -- drug effects KW - Immunoglobulin G -- metabolism KW - Bacterial Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73223451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Histidine+and+aspartic+acid+residues+important+for+immunoglobulin+G+endopeptidase+activity+of+the+group+A+Streptococcus+opsonophagocytosis-inhibiting+Mac+protein.&rft.au=Lei%2C+Benfang%3BLiu%2C+Mengyao%3BMeyers%2C+Elishia+G%3BManning%2C+Heather+M%3BNagiec%2C+Michael+J%3BMusser%2C+James+M&rft.aulast=Lei&rft.aufirst=Benfang&rft.date=2003-05-01&rft.volume=71&rft.issue=5&rft.spage=2881&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 - 2003-05-15 N1 - Date created - 2003-04-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biol Chem. 2001 May;382(5):727-33 [11517925] Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2235-40 [10681429] Clin Microbiol Rev. 2000 Jul;13(3):470-511 [10885988] Infect Immun. 2000 Dec;68(12):6807-18 [11083799] J Biol Chem. 1995 Jul 14;270(28):16645-52 [7622473] Nat Med. 2001 Dec;7(12):1298-305 [11726969] EMBO J. 2002 Apr 2;21(7):1607-15 [11927545] Infect Immun. 2002 Dec;70(12):6880-90 [12438365] Biochemistry. 1981 Jan 6;20(1):48-51 [7470479] Nat Med. 2001 Dec;7(12):1285-6 [11726964] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypersensitivity and idiosyncratic reactions to oxaliplatin. AN - 73216936; 12712487 AB - Oxaliplatin is a third-generation platinum analog that is used to treat a variety of solid tumors, particularly colorectal carcinoma. Patients may develop hypersensitivity reactions, although this complication occurs infrequently. Three patients developed hypersensitivity reactions to oxaliplatin while undergoing treatment on a Phase I trial of oxaliplatin and capecitabine. An Entrez PUBMED search was performed to identify other cases. Two patients experienced the abrupt onset of erythema alone or with pruritus during the 9th and 11th infusions of oxaliplatin, whereas the other patient developed fever and mild dyspnea a few hours after the 9th oxaliplatin infusion. All 3 patients were rechallenged successfully for at least 1 additional oxaliplatin infusion by using oral dexamethasone, 20 mg orally, 6 and 12 hours before the administration of oxaliplatin and by administering intravenously 125 mg of solumedrol, 50 mg of diphenhydramine, and 50 mg of cimetidine 30 minutes before oxaliplatin. The literature review suggests two distinct patterns of reactions: classic hypersensitivity (as experienced by the first two patients) and idiosyncratic reactions (as experienced by the third patient). Patients who develop mild to moderate hypersensitivity to oxaliplatin may be pretreated with steroids and antagonists of Type 1 and 2 histamine receptors, whereas patients who develop severe reactions are unlikely to tolerate further therapy. JF - Cancer AU - Thomas, Rebecca R AU - Quinn, Mary G AU - Schuler, Barbara AU - Grem, Jean L AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, NCI-Navy Medical Oncology, National Naval Medical Center, Bethesda, Maryland 20889-5105, USA. Y1 - 2003/05/01/ PY - 2003 DA - 2003 May 01 SP - 2301 EP - 2307 VL - 97 IS - 9 SN - 0008-543X, 0008-543X KW - Anti-Inflammatory Agents KW - 0 KW - Antiemetics KW - Antineoplastic Agents KW - Histamine H2 Antagonists KW - Organoplatinum Compounds KW - oxaliplatin KW - 04ZR38536J KW - Methylprednisolone Hemisuccinate KW - 5GMR90S4KN KW - Dexamethasone KW - 7S5I7G3JQL KW - Cimetidine KW - 80061L1WGD KW - Diphenhydramine KW - 8GTS82S83M KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Oral KW - Neoplasms -- drug therapy KW - Antiemetics -- therapeutic use KW - Dexamethasone -- therapeutic use KW - Humans KW - Anti-Inflammatory Agents -- therapeutic use KW - Aged KW - Anti-Inflammatory Agents -- administration & dosage KW - Methylprednisolone Hemisuccinate -- therapeutic use KW - Diphenhydramine -- therapeutic use KW - Histamine H2 Antagonists -- administration & dosage KW - Antiemetics -- administration & dosage KW - Diphenhydramine -- administration & dosage KW - Neoplasms -- pathology KW - Adult KW - Cimetidine -- administration & dosage KW - Cimetidine -- therapeutic use KW - Middle Aged KW - Male KW - Female KW - Methylprednisolone Hemisuccinate -- administration & dosage KW - Histamine H2 Antagonists -- therapeutic use KW - Fever -- chemically induced KW - Organoplatinum Compounds -- adverse effects KW - Drug Hypersensitivity -- etiology KW - Dyspnea -- drug therapy KW - Dyspnea -- chemically induced KW - Fever -- drug therapy KW - Erythema -- drug therapy KW - Erythema -- chemically induced KW - Drug Hypersensitivity -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73216936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hypersensitivity+and+idiosyncratic+reactions+to+oxaliplatin.&rft.au=Thomas%2C+Rebecca+R%3BQuinn%2C+Mary+G%3BSchuler%2C+Barbara%3BGrem%2C+Jean+L&rft.aulast=Thomas&rft.aufirst=Rebecca&rft.date=2003-05-01&rft.volume=97&rft.issue=9&rft.spage=2301&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-20 N1 - Date created - 2003-04-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cancer. 2004 Jan 1;100(1):211-2 [14692042] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repair mechanisms for oxidative DNA damage. AN - 73211546; 12700077 AB - Reactive oxygen species are formed as by-products of mitochondrial aerobic respiration, as induced products upon exposure to certain environmental/exogenous agents (e.g. ionizing radiation), or as intended products during the immune response against invading foreign microbes. Although serving as essential signaling molecules in certain biological processes (e.g. during gene activation responses), these chemicals, particularly during oxidative stress when at excessive concentrations, can react with cellular components, most notably DNA, and in this capacity, promote mutagenesis or cell death, and in turn, human disease. We review here several of the common oxidative DNA damages as well as the DNA repair mechanisms related to maintaining genome integrity, and thus, preventing cancer formation and age-related disease. We focus mainly on participants of the base excision repair (BER) pathway. In brief, the steps of BER include: (a) excision of the damaged base, (b) incision of the DNA backbone at the apurinic/apyrimidinic (AP) site product, (c) removal of the AP terminal fragment, (d) gap-filling synthesis, and (e) ligation of the final nick. JF - Frontiers in bioscience : a journal and virtual library AU - Wilson, David M AU - Sofinowski, Troy M AU - McNeill, Daniel R AD - Laboratory of Molecular Gerontology, GRC, National Institute on Aging, IRP, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA. wilsonda@grc.nia.nih.gov Y1 - 2003/05/01/ PY - 2003 DA - 2003 May 01 SP - d963 EP - d981 VL - 8 SN - 1093-9946, 1093-9946 KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Humans KW - DNA Repair -- physiology KW - DNA Damage -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73211546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Frontiers+in+bioscience+%3A+a+journal+and+virtual+library&rft.atitle=Repair+mechanisms+for+oxidative+DNA+damage.&rft.au=Wilson%2C+David+M%3BSofinowski%2C+Troy+M%3BMcNeill%2C+Daniel+R&rft.aulast=Wilson&rft.aufirst=David&rft.date=2003-05-01&rft.volume=8&rft.issue=&rft.spage=d963&rft.isbn=&rft.btitle=&rft.title=Frontiers+in+bioscience+%3A+a+journal+and+virtual+library&rft.issn=10939946&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-02-11 N1 - Date created - 2003-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of inducible nitric oxide synthase and elevation of tyrosine nitration of a 32-kilodalton cellular protein in brain capillary endothelial cells from rats infected with a neuropathogenic murine leukemia virus. AN - 73210529; 12692217 AB - PVC-211 murine leukemia virus (MuLV) is a neuropathogenic variant of Friend MuLV (F-MuLV) which causes a rapidly progressive spongiform neurodegenerative disease in rodents. The primary target of PVC-211 MuLV infection in the brain is the brain capillary endothelial cell (BCEC), which is resistant to F-MuLV infection. Previous studies have shown that changes in the envelope gene of PVC-211 MuLV confer BCEC tropism to the virus. However, little is known about how infection of BCECs by PVC-211 MuLV induces neurological disease. Previous results suggest that nitric oxide (NO), which has been implicated as a potential neurotoxin, is involved in PVC-211 MuLV-induced neurodegeneration. In this study, we show that expression of inducible nitric oxide synthase (iNOS), which produces NO from L-arginine, is induced in BCECs from PVC-211 MuLV-infected rats. Furthermore, elevated levels of a 32-kDa cellular protein modified by 3-nitrotyrosine, which is a hallmark of NO production, were observed in virus-infected BCECs. BCECs from rats infected with BCEC-tropic but nonneuropathogenic PVF-e5 MuLV, which is a chimeric virus between PVC-211 MuLV and F-MuLV, fail to induce either iNOS expression or elevation of tyrosine nitration of a 32-kDa protein. These results suggest that expression of iNOS and nitration of tyrosine residues of a 32-kDa protein in PVC-211 MuLV-infected BCECs may play an important role in neurological disease induction. JF - Journal of virology AU - Jinno-Oue, Atsushi AU - Wilt, Susan G AU - Hanson, Charlotte AU - Dugger, Natalie V AU - Hoffman, Paul M AU - Masuda, Michiaki AU - Ruscetti, Sandra K AD - Basic Research Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 5145 EP - 5151 VL - 77 IS - 9 SN - 0022-538X, 0022-538X KW - Proteins KW - 0 KW - 3-nitrotyrosine KW - 3604-79-3 KW - Tyrosine KW - 42HK56048U KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, mouse KW - Nos2 protein, rat KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Tumor Virus Infections -- virology KW - Capillaries -- virology KW - Nervous System -- virology KW - Retroviridae Infections -- physiopathology KW - Mice KW - Nervous System -- pathology KW - Rats KW - Retroviridae Infections -- virology KW - Rats, Inbred F344 KW - Tumor Virus Infections -- physiopathology KW - Cells, Cultured KW - Endothelium, Vascular -- enzymology KW - Endothelium, Vascular -- metabolism KW - Endothelium, Vascular -- cytology KW - Brain -- blood supply KW - Brain -- metabolism KW - Brain -- virology KW - Proteins -- metabolism KW - Nitric Oxide Synthase -- biosynthesis KW - Brain -- enzymology KW - Endothelium, Vascular -- virology KW - Tyrosine -- metabolism KW - Leukemia Virus, Murine -- pathogenicity KW - Tyrosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73210529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Expression+of+inducible+nitric+oxide+synthase+and+elevation+of+tyrosine+nitration+of+a+32-kilodalton+cellular+protein+in+brain+capillary+endothelial+cells+from+rats+infected+with+a+neuropathogenic+murine+leukemia+virus.&rft.au=Jinno-Oue%2C+Atsushi%3BWilt%2C+Susan+G%3BHanson%2C+Charlotte%3BDugger%2C+Natalie+V%3BHoffman%2C+Paul+M%3BMasuda%2C+Michiaki%3BRuscetti%2C+Sandra+K&rft.aulast=Jinno-Oue&rft.aufirst=Atsushi&rft.date=2003-05-01&rft.volume=77&rft.issue=9&rft.spage=5145&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-27 N1 - Date created - 2003-04-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell Death Differ. 1999 Oct;6(10):943-51 [10556970] J Neurochem. 1999 Aug;73(2):727-35 [10428070] J Neurovirol. 1999 Dec;5(6):556-69 [10602397] Curr Opin Immunol. 2000 Feb;12(1):20-6 [10679411] Neurosci Lett. 2000 Sep 8;291(1):44-8 [10962150] J Neurosci Res. 2000 Nov 1;62(3):440-50 [11054813] Mol Cell Biochem. 2000 Nov;214(1-2):121-9 [11195783] Trends Neurosci. 2001 Mar;24(3):162-9 [11182456] J Immunol. 2001 Apr 15;166(8):5168-75 [11290800] Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2281-6 [11854525] J Neurosci. 2002 Apr 1;22(7):2478-86 [11923412] J Biol Chem. 2002 May 17;277(20):17415-27 [11877405] J Clin Invest. 2002 May;109(10):1311-9 [12021246] Virology. 1970 Dec;42(4):1136-9 [4099080] In Vitro. 1981 Apr;17(4):353-62 [6263791] J Virol. 1984 Jun;50(3):970-3 [6328027] Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620-4 [2154753] Pharmacol Rev. 1991 Jun;43(2):109-42 [1852778] J Biol Chem. 1991 Dec 5;266(34):22789-91 [1720773] J Virol. 1992 May;66(5):2798-806 [1560524] Lab Invest. 1992 Sep;67(3):314-21 [1405490] J Biol Chem. 1992 Nov 25;267(33):23617-24 [1429703] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10945-9 [1279698] J Virol. 1993 Aug;67(8):4580-7 [8392599] J Biol Chem. 1994 Feb 18;269(7):4705-8 [7508926] Hypertension. 1994 Jun;23(6 Pt 2):1121-31 [7515853] Cell. 1994 Sep 23;78(6):915-8 [7522969] Annu Rev Biochem. 1994;63:175-95 [7526779] Neuropharmacology. 1994 Nov;33(11):1235-44 [7870284] J Neuropathol Exp Neurol. 1999 Nov;58(11):1163-9 [10560659] Brain Res Brain Res Rev. 1995 Mar;20(3):269-87 [7550361] Virology. 1996 Jan 15;215(2):142-51 [8560761] Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3377-82 [8622943] Am J Pathol. 1996 Jul;149(1):21-8 [8686745] J Biol Chem. 1996 Aug 9;271(32):19199-208 [8702599] Chem Res Toxicol. 1996 Jul-Aug;9(5):836-44 [8828918] J Virol. 1998 Jun;72(6):4547-51 [9573217] J Biol Chem. 1998 Jun 5;273(23):14085-9 [9603906] Am J Physiol. 1998 Sep;275(3 Pt 1):G592-603 [9724273] Chem Res Toxicol. 1998 Sep;11(9):1067-74 [9760281] Science. 1998 Dec 11;282(5396):2085-8 [9851930] Prog Brain Res. 1998;118:215-29 [9932444] Brain Res. 1999 Mar 27;823(1-2):177-82 [10095024] J Immunol. 1999 Apr 1;162(7):4319-27 [10201964] Nat Med. 1999 Dec;5(12):1403-9 [10581083] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New insights into the immunopathogenesis and treatment of small vessel vasculitis of the kidney. AN - 73208706; 12698064 AB - Glomerulonephritis is an important manifestation of small vessel vasculitides such as Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Renal involvement in these diseases is characterized by a pauci-immune segmental necrotizing and crescentic glomerulonephritis that is strongly associated with circulating antineutrophil cytoplasmic autoantibodies. We will review recent advances in understanding the pathogenesis of antineutrophil cytoplasmic autoantibody-related renal vasculitides and innovative approaches to their treatment. An experimental milestone in antineutrophil cytoplasmic autoantibody research has been reached in the past year. Using an innovative mouse model, investigators from the University of North Carolina in Chapel Hill have recently acquired robust data supporting the pathogenic role of antineutrophil cytoplasmic autoantibodies in the glomerulonephritis and small vessel vasculitis, analogous to those seen in microscopic polyangiitis and Wegener granulomatosis. Novel immunosuppressive approaches have been examined including preliminary studies using biologic agents, such as antagonists of tumor necrosis factor and monoclonal antibodies to B lymphocytes. Recent insights into the pathogenesis of antineutrophil cytoplasmic autoantibody-related vascular injury and the availability of new biologic, immune response modifiers to complement standard chemical immunosuppressive agents offer exciting new prospects for investigation in the management of patients with small vessel renal vasculitides. JF - Current opinion in nephrology and hypertension AU - Langford, Carol A AU - Balow, James E AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-1818, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 267 EP - 272 VL - 12 IS - 3 SN - 1062-4821, 1062-4821 KW - Adjuvants, Immunologic KW - 0 KW - Antibodies, Antineutrophil Cytoplasmic KW - Antibodies, Monoclonal KW - Antibodies, Monoclonal, Murine-Derived KW - Rituximab KW - 4F4X42SYQ6 KW - Cyclophosphamide KW - 8N3DW7272P KW - Mycophenolic Acid KW - HU9DX48N0T KW - Azathioprine KW - MRK240IY2L KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Animals KW - Antibodies, Antineutrophil Cytoplasmic -- metabolism KW - Azathioprine -- therapeutic use KW - Humans KW - Disease Models, Animal KW - Mice KW - Antibodies, Monoclonal -- therapeutic use KW - Cyclophosphamide -- therapeutic use KW - Methotrexate -- therapeutic use KW - Kidney -- blood supply KW - Adjuvants, Immunologic -- therapeutic use KW - Mycophenolic Acid -- analogs & derivatives KW - Mycophenolic Acid -- therapeutic use KW - Vasculitis -- etiology KW - Vasculitis -- immunology KW - Kidney Diseases -- therapy KW - Kidney Diseases -- immunology KW - Kidney Diseases -- etiology KW - Vasculitis -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73208706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+nephrology+and+hypertension&rft.atitle=New+insights+into+the+immunopathogenesis+and+treatment+of+small+vessel+vasculitis+of+the+kidney.&rft.au=Langford%2C+Carol+A%3BBalow%2C+James+E&rft.aulast=Langford&rft.aufirst=Carol&rft.date=2003-05-01&rft.volume=12&rft.issue=3&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+nephrology+and+hypertension&rft.issn=10624821&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-26 N1 - Date created - 2003-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins containing Pseudomonas exotoxin A: a short history. AN - 73196961; 12700949 JF - Cancer immunology, immunotherapy : CII AU - Pastan, Ira AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, 37 Convent Drive, Room 5106, Bethesda, MD 20892-4268, USA. pastani@pop.nci.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 338 EP - 341 VL - 52 IS - 5 SN - 0340-7004, 0340-7004 KW - Bacterial Toxins KW - 0 KW - Exotoxins KW - Immunotoxins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Endosomes -- immunology KW - Humans KW - Clinical Trials as Topic KW - Models, Biological KW - Immunotoxins -- chemistry KW - ADP Ribose Transferases -- immunology KW - Immunotoxins -- therapeutic use KW - Exotoxins -- immunology KW - Bacterial Toxins -- immunology KW - Virulence Factors -- immunology KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73196961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+immunology%2C+immunotherapy+%3A+CII&rft.atitle=Immunotoxins+containing+Pseudomonas+exotoxin+A%3A+a+short+history.&rft.au=Pastan%2C+Ira&rft.aulast=Pastan&rft.aufirst=Ira&rft.date=2003-05-01&rft.volume=52&rft.issue=5&rft.spage=338&rft.isbn=&rft.btitle=&rft.title=Cancer+immunology%2C+immunotherapy+%3A+CII&rft.issn=03407004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-25 N1 - Date created - 2003-04-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression of the human CYP3A4 gene in the small intestine of transgenic mice: in vitro metabolism and pharmacokinetics of midazolam. AN - 73191189; 12695342 AB - Human cytochrome P450 3A4 (CYP3A4) is the most abundant hepatic and intestinal phase I drug-metabolizing enzyme, and participates in the oxidative metabolism of approximately 50% of drugs on the market. In the present study, a transgenic-CYP3A4 (Tg-CYP3A4) mouse model that expresses CYP3A4 in the intestine and is phenotypically normal was generated, which was genotyped by both polymerase chain reaction and Southern blotting. Intestinal microsomes prepared from Tg-CYP3A4 mice metabolized midazolam (MDZ) to 1'-hydroxymidazolam about 2 times, and to 4-hydroxymidazolam around 3 times faster than that from wild-type (WT) mice. These increased MDZ hydroxylation activities were completely inhibited by an anti-CYP3A4 monoclonal antibody. The time course of plasma MDZ and its metabolite concentrations was measured after intravenous (0.25 mg/kg) and oral (2.5 mg/kg) administration of MDZ, and pharmacokinetic parameters were estimated by fitting to a noncompartmental model. Pretreatment with ketoconazole increased orally dosed MDZ maximum plasma concentration (C(max)), time of the maximum concentration, area under the plasma concentration-time curve from zero to infinity (AUC(0- infinity)), and elimination half-life (t(1/2)) to 3.2-, 1.7-, 7.7-, 2-fold, and decreased MDZ apparent oral clearance about 8-fold in Tg-CYP3A4 mice. The ratios of MDZ C(max), AUC(0- infinity), t(1/2) and bioavailability between Tg-CYP3A4 and WT mice after the oral dose of MDZ were 0.3, 0.6, 0.5, and 0.5, respectively. These results suggest that this Tg-CYP3A4 mouse would be an appropriate in vivo animal model for the evaluation of human intestine CYP3A4 metabolism of drug candidates and potential food-drug and drug-drug interactions in preclinical drug development. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Granvil, Camille P AU - Yu, Ai-Ming AU - Elizondo, Guillermo AU - Akiyama, Taro E AU - Cheung, Connie AU - Feigenbaum, Lionel AU - Krausz, Kristopher W AU - Gonzalez, Frank J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 548 EP - 558 VL - 31 IS - 5 SN - 0090-9556, 0090-9556 KW - Enzyme Inhibitors KW - 0 KW - 4-hydroxymidazolam KW - 59468-85-8 KW - Dexamethasone KW - 7S5I7G3JQL KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - 1-hydroxymethylmidazolam KW - E5142BN92Z KW - CYP3A4 protein, human KW - EC 1.14.13.67 KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - Midazolam KW - R60L0SM5BC KW - Ketoconazole KW - R9400W927I KW - Rifampin KW - VJT6J7R4TR KW - Index Medicus KW - Administration, Oral KW - Animals KW - Drug Interactions KW - Area Under Curve KW - Dexamethasone -- pharmacology KW - Humans KW - Mice KW - Mice, Transgenic KW - Biological Availability KW - Polymerase Chain Reaction KW - Half-Life KW - Blotting, Southern KW - Microsomes -- metabolism KW - In Vitro Techniques KW - Enzyme Inhibitors -- pharmacology KW - Rifampin -- pharmacology KW - Time Factors KW - Ketoconazole -- pharmacology KW - Male KW - Microsomes -- drug effects KW - Midazolam -- analogs & derivatives KW - Midazolam -- blood KW - Cytochrome P-450 Enzyme System -- genetics KW - Midazolam -- pharmacokinetics KW - Intestine, Small -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Midazolam -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73191189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.atitle=Expression+of+the+human+CYP3A4+gene+in+the+small+intestine+of+transgenic+mice%3A+in+vitro+metabolism+and+pharmacokinetics+of+midazolam.&rft.au=Granvil%2C+Camille+P%3BYu%2C+Ai-Ming%3BElizondo%2C+Guillermo%3BAkiyama%2C+Taro+E%3BCheung%2C+Connie%3BFeigenbaum%2C+Lionel%3BKrausz%2C+Kristopher+W%3BGonzalez%2C+Frank+J&rft.aulast=Granvil&rft.aufirst=Camille&rft.date=2003-05-01&rft.volume=31&rft.issue=5&rft.spage=548&rft.isbn=&rft.btitle=&rft.title=Drug+metabolism+and+disposition%3A+the+biological+fate+of+chemicals&rft.issn=00909556&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-10 N1 - Date created - 2003-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of novel syncytium-inducing and host range variants of ecotropic moloney murine leukemia virus in Mus spicilegus. AN - 73185787; 12692209 AB - Mus spicilegus is an Eastern European wild mouse species that has previously been reported to harbor an unusual infectious ecotropic murine leukemia virus (MLV) and proviral envelope genes of a novel MLV subgroup. In the present study, M. spicilegus neonates were inoculated with Moloney ecotropic MLV (MoMLV). All 17 inoculated mice produced infectious ecotropic virus after 8 to 14 weeks, and two unusual phenotypes distinguished the isolates from MoMLV. First, most of the M. spicilegus isolates grew to equal titers on M. dunni and SC-1 cells, although MoMLV does not efficiently infect M. dunni cells. The deduced amino acid sequence of a representative clone differed from MoMLV by insertion of two serine residues within the VRA of SUenv. Modification of a molecular clone of MoMLV by the addition of these serines produced a virus that grows to high titer in M. dunni cells, establishing a role for these two serine residues in host range. A second unusual phenotype was found in only one of the M. spicilegus isolates, Spl574. Spl574 produces large syncytia of multinucleated giant cells in M. dunni cells, but its replication is restricted in other mouse cell lines. Sequencing and mutagenesis demonstrated that syncytium formation could be attributed to a single amino acid substitution within VRA, S82F. Thus, viruses with altered growth properties are selected during growth in M. spicilegus. The mutations associated with the host range and syncytium-inducing variants map to a key region of VRA known to govern interactions with the cell surface receptor, suggesting that the associated phenotypes may result from altered interactions with the unusual ecotropic virus mCAT1 receptor carried by M. dunni. JF - Journal of virology AU - Jung, Yong Tae AU - Kozak, Christine A AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0460, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 5065 EP - 5072 VL - 77 IS - 9 SN - 0022-538X, 0022-538X KW - Receptors, Virus KW - 0 KW - Viral Envelope Proteins KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Tumor Virus Infections -- virology KW - Amino Acid Sequence KW - Leukemia, Experimental -- virology KW - Mice KW - Receptors, Virus -- metabolism KW - Sequence Analysis, DNA KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Retroviridae Infections -- virology KW - Molecular Sequence Data KW - Viral Envelope Proteins -- metabolism KW - Cell Line KW - Viral Envelope Proteins -- genetics KW - Muridae -- virology KW - Moloney murine leukemia virus -- pathogenicity KW - Giant Cells -- physiology KW - Moloney murine leukemia virus -- physiology KW - Moloney murine leukemia virus -- classification KW - Moloney murine leukemia virus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73185787?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Generation+of+novel+syncytium-inducing+and+host+range+variants+of+ecotropic+moloney+murine+leukemia+virus+in+Mus+spicilegus.&rft.au=Jung%2C+Yong+Tae%3BKozak%2C+Christine+A&rft.aulast=Jung&rft.aufirst=Yong&rft.date=2003-05-01&rft.volume=77&rft.issue=9&rft.spage=5065&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-27 N1 - Date created - 2003-04-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Genet. 2000 Jan;24(1):23-5 [10615122] J Virol. 1999 May;73(5):4327-40 [10196331] J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] Virology. 1970 Dec;42(4):1136-9 [4099080] Virology. 1975 May;65(1):128-34 [167514] J Virol. 1981 Jan;37(1):181-90 [6260972] J Virol. 1984 Nov;52(2):695-8 [6092693] J Virol. 1985 Aug;55(2):281-5 [2991555] J Virol. 1985 Sep;55(3):768-77 [2991595] J Virol. 1987 Oct;61(10):3082-8 [3041030] Virology. 1988 Aug;165(2):469-75 [2841796] Virology. 1989 Nov;173(1):58-67 [2554579] J Virol. 1991 Nov;65(11):5975-82 [1717711] J Virol. 1993 Jan;67(1):67-74 [8416389] J Virol. 1993 Apr;67(4):2091-6 [8445722] J Virol. 1993 Jul;67(7):4056-61 [8510216] J Virol. 1994 Feb;68(2):626-31 [8289366] J Virol. 1994 Mar;68(3):1773-81 [8107239] J Virol. 1994 Nov;68(11):7516-24 [7933135] Science. 1997 Sep 12;277(5332):1662-6 [9287219] J Virol. 1999 May;73(5):3758-63 [10196270] Virology. 2001 Nov 10;290(1):39-49 [11883004] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel marine and microbial natural product inhibitors of vacuolar ATPase. AN - 73176271; 12678782 AB - Vacuolar-ATPase (V-ATPase) has been proposed as a drug target in osteoporosis due to its involvement in bone resorption, and as a target in cancer due to potential involvement in tumor invasion and metastasis. The classical selective inhibitors of V-ATPase are microbial macrolides of the bafilomycin and concanamycin class. These inhibitors have proven to be too toxic for therapeutic use, however recent structure-activity studies on bafilomycins, and the isolation of novel macrolide structures from marine sources, have provided new avenues for development of potentially less toxic V-ATPase inhibitors. The novel salicylihalamide and lobatamide series of compounds were predicted to share a common mechanism of action based on the patterns of cytotoxicity produced in the NCI 60-cell cancer screen. They have subsequently been shown to selectively interact with mammalian V-ATPases, but not with fungal V-ATPases. With the recent achievement of total syntheses of salicylihalamide, lobatamide, and related compounds, the elaboration of congeners with specificity for particular enzyme isoforms may provide drug candidates which are less toxic. This review summarizes recent advances in V-ATPase inhibition and the prospects for further progress. JF - Current medicinal chemistry AU - Beutler, John A AU - McKee, Tawnya C AD - Molecular Targets Discovery Program, Center for Cancer Research, National Cancer Institute, NCI-Frederick, Frederick, MD 21702-1201, USA. manuscripts@mail.ncifcrf.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 787 EP - 796 VL - 10 IS - 9 SN - 0929-8673, 0929-8673 KW - Antineoplastic Agents KW - 0 KW - Biological Factors KW - Enzyme Inhibitors KW - Vacuolar Proton-Translocating ATPases KW - EC 3.6.1.- KW - Index Medicus KW - Drug Delivery Systems KW - Animals KW - Fungi -- chemistry KW - Humans KW - Antineoplastic Agents -- isolation & purification KW - Marine Biology KW - Antineoplastic Agents -- chemistry KW - Antineoplastic Agents -- pharmacology KW - Bacteria -- chemistry KW - Structure-Activity Relationship KW - Biological Factors -- chemistry KW - Biological Factors -- isolation & purification KW - Enzyme Inhibitors -- chemistry KW - Vacuolar Proton-Translocating ATPases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Inhibitors -- isolation & purification KW - Biological Factors -- pharmacology KW - Vacuolar Proton-Translocating ATPases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73176271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+medicinal+chemistry&rft.atitle=Novel+marine+and+microbial+natural+product+inhibitors+of+vacuolar+ATPase.&rft.au=Beutler%2C+John+A%3BMcKee%2C+Tawnya+C&rft.aulast=Beutler&rft.aufirst=John&rft.date=2003-05-01&rft.volume=10&rft.issue=9&rft.spage=787&rft.isbn=&rft.btitle=&rft.title=Current+medicinal+chemistry&rft.issn=09298673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-14 N1 - Date created - 2003-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Desensitization of the photoresponse in Limulus ventral photoreceptors by protein kinase C precedes rhabdomere disorganization and endocytosis. AN - 71294587; 14570246 AB - Limulus photoreceptors utilize the phosphoinositide pathway to generate light-induced single photon events (quantum bumps) that sum to form the depolarizing receptor potential. The protein kinase C (PKC) activator, (-)-indolactam V (ILV) rapidly desensitizes the light response in Limulus ventral nerve photoreceptors. Within 10 min of extracellular application, 100 nM (-)-ILV caused a decrease in the mean amplitude of quantum bumps to 38% of control values. PKC activation by (-)-ILV also causes photosensitive membrane disorganization and endocytosis. To investigate whether this precedes desensitization of the electrical response, we fixed cells after 10-min incubation with 25 microM (-)-ILV, a concentration sufficient to cause a 1000-fold desensitization of the receptor potential. The photosensitive microvilli of these photoreceptors remained narrow, densely packed, and well organized. Increasing the incubation time to 60 min did, however, induce disorganization and swelling of the microvilli and endocytosis of the photosensitive membrane, as previously reported. Measurement of membrane capacitance did not indicate a significant reduction in membrane area accompanying desensitization by (-)-ILV. PKC-induced reduction in light sensitivity therefore precedes the detection of ultrastructural changes in the rhabdomeral membrane and is not due to a net loss of membrane. JF - Visual neuroscience AU - Dabdoub, Alain AU - Jinks, Robert N AU - Wang, Youjun AU - Battelle, Barbara-Anne AU - Payne, Richard AD - National Institutes of Health, NIDCD, Rockville, USA. PY - 2003 SP - 241 EP - 248 VL - 20 IS - 3 SN - 0952-5238, 0952-5238 KW - Indoles KW - 0 KW - Lactams KW - indolactam V KW - 8CIY9O1323 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Animals KW - Microvilli -- ultrastructure KW - Enzyme Activation -- physiology KW - Microscopy, Electron KW - Indoles -- pharmacology KW - Time Factors KW - Fluorescent Antibody Technique KW - Lactams -- pharmacology KW - Retina -- cytology KW - Protein Kinase C -- metabolism KW - Retina -- ultrastructure KW - Photoreceptor Cells -- drug effects KW - Retina -- physiology KW - Photoreceptor Cells -- radiation effects KW - Light KW - Protein Kinase C -- physiology KW - Photoreceptor Cells -- ultrastructure KW - Endocytosis -- physiology KW - Horseshoe Crabs -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71294587?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Visual+neuroscience&rft.atitle=Desensitization+of+the+photoresponse+in+Limulus+ventral+photoreceptors+by+protein+kinase+C+precedes+rhabdomere+disorganization+and+endocytosis.&rft.au=Dabdoub%2C+Alain%3BJinks%2C+Robert+N%3BWang%2C+Youjun%3BBattelle%2C+Barbara-Anne%3BPayne%2C+Richard&rft.aulast=Dabdoub&rft.aufirst=Alain&rft.date=2003-05-01&rft.volume=20&rft.issue=3&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Visual+neuroscience&rft.issn=09525238&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-30 N1 - Date created - 2003-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Does quality of child care affect child outcomes at age 4 1/2? AN - 57200314; 227492 AB - Research reveals associations between child-care quality and child outcomes. But are these associations causal? Data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care, a longitudinal study of children from birth to age 4 1/2, were used to explore 5 propositions that would support a causal argument. Three propositions received support, principally in the cognitive domain: (a) Associations between quality and outcomes remained even with child and family factors controlled; (b) associations between care and outcomes were domain specific; and (c) outcomes were predicted by quality of earlier care with concurrent care controlled. The 4th proposition, that associations between quality and outcomes would be significant with earlier abilities controlled, received limited support. There was no support for the 5th proposition, that quality and outcomes would exhibit dose-response relations. (Original abstract) JF - Developmental Psychology AU - NICHD Early Child Care Research Network AD - NICHD Early Child Care Research Network Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 451 EP - 469 VL - 39 IS - 3 SN - 0012-1649, 0012-1649 KW - Longitudinal studies KW - USA KW - Quality of care KW - Preschool children KW - Development KW - Child care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57200314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+Psychology&rft.atitle=Does+quality+of+child+care+affect+child+outcomes+at+age+4+1%2F2%3F&rft.au=NICHD+Early+Child+Care+Research+Network&rft.aulast=NICHD+Early+Child+Care+Research+Network&rft.aufirst=&rft.date=2003-05-01&rft.volume=39&rft.issue=3&rft.spage=451&rft.isbn=&rft.btitle=&rft.title=Developmental+Psychology&rft.issn=00121649&rft_id=info:doi/ LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2003-09-22 N1 - Document feature - refs. tbls. N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Preschool children; Development; Child care; Quality of care; Longitudinal studies; USA ER - TY - JOUR T1 - Do children's attention processes mediate the link between family predictors and school readiness? AN - 57193247; 227502 AB - The role of attention processes as possible mediators, between family environment and school readiness was analyzed with data from 1,002 children and their families. Data on children's sustained attention, impulsivity, and school readiness (i.e., cognitive, achievement, language, and social development) were obtained at 54 months of age, and quality of the family environment was assessed throughout the first 54 months. Mediation tests showed that children's sustained attention partially accounted for the link between family environment and achievement and language outcomes. Impulsivity partially accounted for the link between family environment and achievement, social competence, and externalizing behaviors. The roles of sustained attention and of inhibition of impulsive responding in the relation between family characteristics and school readiness are discussed. (Original abstract) JF - Developmental Psychology AU - NICHD Early Child Care Research Network AD - NICHD Early Child Care Research Network Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 581 EP - 593 VL - 39 IS - 3 SN - 0012-1649, 0012-1649 KW - Family environment KW - Young children KW - Sustained attention KW - Social competence KW - School readiness KW - Impulsivity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57193247?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+Psychology&rft.atitle=Do+children%27s+attention+processes+mediate+the+link+between+family+predictors+and+school+readiness%3F&rft.au=NICHD+Early+Child+Care+Research+Network&rft.aulast=NICHD+Early+Child+Care+Research+Network&rft.aufirst=&rft.date=2003-05-01&rft.volume=39&rft.issue=3&rft.spage=581&rft.isbn=&rft.btitle=&rft.title=Developmental+Psychology&rft.issn=00121649&rft_id=info:doi/ LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2003-09-22 N1 - Document feature - refs. tbls. N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Young children; School readiness; Social competence; Family environment; Sustained attention; Impulsivity ER - TY - JOUR T1 - Doppler transmitral flow indexes and risk of atrial fibrillation (The Framingham Heart Study) AN - 230392717; 12714150 AB - Atrial fibrillation (AF) is characterized by structural remodeling and atrial systolic failure. It is unclear if atrial filling abnormalities precede the onset of AF. We evaluated 942 Framingham Study subjects (587 women; mean age 75 years) who underwent Doppler echocardiographic evaluation at a routine examination and who did not have a history of AF. We used multivariable Cox regression models (stratified by gender and prevalent cardiovascular disease) to examine the relations of Doppler transmitral flow indexes (ratio of the velocity–time integrals of the early [E] and late [A] diastolic filling waves [VTI E/A], a correlate of atrial conduit function; E-wave deceleration time; the atrial filling fraction, an index of atrial systolic function; and peak A wave velocity) to the incidence of AF. At follow-up (mean 7 years), 85 subjects (41 women) developed AF. In models adjusting for established risk factors for AF (including left atrial size) at baseline, and for heart failure and myocardial infarction on follow-up, a 1 SD increment in VTI E/A was associated with a 28% increase in risk of AF (hazards ratio 1.28, 95% confidence interval 1.02 to 1.59). A 1 SD decrease in the atrial filling fraction was associated with a 28% higher risk of AF (hazards ratio 1.28, 95% confidence interval 0.98 to 1.67). There was a U-shaped relation between peak A-wave velocity and risk of AF. Thus, in our elderly community-based sample, increased VTI E/A and a low atrial filling fraction were markers of increased risk of AF, suggesting that altered atrial filling may antedate AF. JF - The American Journal of Cardiology AU - Vasan, Ramachandran S AU - Larson, Martin G AU - Levy, Daniel AU - Galderisi, Maurizio AU - et al Y1 - 2003/05/01/ PY - 2003 DA - 2003 May 01 SP - 1079 EP - 83 CY - New York PB - Elsevier Sequoia S.A. VL - 91 IS - 9 SN - 00029149 KW - Medical Sciences--Cardiovascular Diseases KW - Health risk assessment KW - Heart KW - Studies KW - Cardiovascular disease KW - Mitral Valve -- ultrasonography KW - Risk Factors KW - Humans KW - Echocardiography, Doppler KW - Aged KW - Male KW - Female KW - Proportional Hazards Models KW - Multivariate Analysis KW - Atrial Function, Left KW - Heart Atria -- ultrasonography KW - Mitral Valve -- physiology KW - Atrial Fibrillation -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/230392717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Cardiology&rft.atitle=Doppler+transmitral+flow+indexes+and+risk+of+atrial+fibrillation+%28The+Framingham+Heart+Study%29&rft.au=Vasan%2C+Ramachandran+S%3BLarson%2C+Martin+G%3BLevy%2C+Daniel%3BGalderisi%2C+Maurizio%3Bet+al&rft.aulast=Vasan&rft.aufirst=Ramachandran&rft.date=2003-05-01&rft.volume=91&rft.issue=9&rft.spage=1079&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Cardiology&rft.issn=00029149&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright Elsevier Sequoia S.A. May 1, 2003 N1 - Last updated - 2013-02-05 N1 - CODEN - AJCDAG ER - TY - JOUR T1 - NEUROPSYCHOLOGICAL AND NEUROIMAGING PERSPECTIVES ON CONCEPTUAL KNOWLEDGE: AN INTRODUCTION AN - 20665213; 9392450 AB - Abstract not available. JF - Cognitive Neuropsychology AU - Martin, Alex AU - Caramazza, Alfonso AD - National Institute of Mental Health, Bethesda, USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 195 EP - 212 PB - Psychology Press VL - 20 IS - 3 SN - 0264-3294, 0264-3294 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Neuroimaging KW - Cognitive ability KW - N3 11001:Behavioral and Cognitive Neuroscience KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20665213?accountid=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=Cognitive+Neuropsychology&rft.atitle=NEUROPSYCHOLOGICAL+AND+NEUROIMAGING+PERSPECTIVES+ON+CONCEPTUAL+KNOWLEDGE%3A+AN+INTRODUCTION&rft.au=Martin%2C+Alex%3BCaramazza%2C+Alfonso&rft.aulast=Martin&rft.aufirst=Alex&rft.date=2003-05-01&rft.volume=20&rft.issue=3&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Cognitive+Neuropsychology&rft.issn=02643294&rft_id=info:doi/10.1080%2F02643290342000050 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-06-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Neuroimaging; Cognitive ability DO - http://dx.doi.org/10.1080/02643290342000050 ER - TY - JOUR T1 - Gourmand savants and environmental determinants of obesity AN - 19435402; 6627570 AB - Obesity is an embodiment of a multifactorial problem with several intermediates in its casual pathway. Virtually all who have written on obesity have responded to four inter-related factors: genetic, perinatal, environmental, and consumption-expenditure energy imbalance. The message to take home is that while a molecular description of each participant of the obesity machinery seems achievable in principle, a complex model describing all of them is currently beyond our grasp. That is why the eradication of the obesity epidemic is seen in a more precise neuropsychological description of what is wrong with each subset of patients. This review proposes that the neuropsychiatric experience might be the most fundamental for it could help to refocus the view of obesity from 'traditional' environmental factors and lifestyle changes to those dominated by a more 'individual-centred' perspective in which different modes of causal attribution are appropriate. This review advocates the idea of environmental dependency as a determinant of obesity, which has been an important idea in neurosciences for more than 30 years with roots in three important areas: psychological, neuropsychiatric, and experimental. The neuropsychology of obesity is yet to become part of today's agenda of obesity research. JF - Obesity Reviews AU - Myslobodsky, M AD - Address M Myslobodsky, Clinical Brain Disorders Branch, NIMH National Institutes of Health, 10 Center Drive, 4S-235 (MSC 1379), Bethesda, MD 20892-1379, USA, myslobom@codon.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 121 EP - 128 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 4 IS - 2 SN - 1467-7881, 1467-7881 KW - Physical Education Index KW - Obesity KW - Genetics KW - Experience KW - Home KW - Attribution KW - Psychology KW - Patients KW - Perspective KW - Lifestyle KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19435402?accountid=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=Obesity+Reviews&rft.atitle=Gourmand+savants+and+environmental+determinants+of+obesity&rft.au=Myslobodsky%2C+M&rft.aulast=Myslobodsky&rft.aufirst=M&rft.date=2003-05-01&rft.volume=4&rft.issue=2&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Obesity+Reviews&rft.issn=14677881&rft_id=info:doi/10.1046%2Fj.1467-789X.2003.00098.x LA - English DB - Physical Education Index N1 - Date revised - 2007-06-01 N1 - SuppNotes - References, 37. N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Experience; Genetics; Obesity; Attribution; Home; Psychology; Patients; Perspective; Lifestyle DO - http://dx.doi.org/10.1046/j.1467-789X.2003.00098.x ER - TY - JOUR T1 - Generation and evaluation of a high-growth reassortant H9N2 influenza A virus as a pandemic vaccine candidate AN - 18848002; 5605200 AB - H9N2 subtype avian influenza viruses (AIVs) are widely distributed in avian species and were isolated from humans in Hong Kong and Guangdong province, China in 1999 raising concern of their potential for pandemic spread. We generated a high-growth reassortant virus (G9/PR8) that contains the hemagglutinin (HA) and neuraminidase (NA) genes from the H9N2 avian influenza virus A/chicken/Hong Kong/G9/97 (G9) and six internal genes from A/Puerto Rico/8/34 (PR8) by genetic reassortment, for evaluation as a potential vaccine candidate in humans. Pathogenicity studies showed that the G9/PR8 reassortant was not highly pathogenic for mice or chickens. Two doses of a formalin-inactivated G9/PR8 virus vaccine induced hemagglutination inhibiting antibodies and conferred complete protection against challenge with G9 and the antigenically distinct H9N2 A/Hong Kong/1073/99 (G1-like) virus in a mouse model. These results indicate that the high growth G9/PR8 reassortant has properties that are desirable in a vaccine seed virus and is suitable for evaluation in humans for use in the event of an H9 pandemic. JF - Vaccine AU - Chen, H AU - Subbarao, K AU - Swayne, D AU - Chen, Q AU - Lu, X AU - Katz, J AU - Cox, N AU - Matsuoka, Y AD - Influenza Branch, Mailstop G-16, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA, ksubbarao@niaid.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 1983 EP - 1988 VL - 21 IS - 17-18 SN - 0264-410X, 0264-410X KW - man KW - Virology & AIDS Abstracts; Immunology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - A 01097:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18848002?accountid=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=Vaccine&rft.atitle=Generation+and+evaluation+of+a+high-growth+reassortant+H9N2+influenza+A+virus+as+a+pandemic+vaccine+candidate&rft.au=Chen%2C+H%3BSubbarao%2C+K%3BSwayne%2C+D%3BChen%2C+Q%3BLu%2C+X%3BKatz%2C+J%3BCox%2C+N%3BMatsuoka%2C+Y&rft.aulast=Chen&rft.aufirst=H&rft.date=2003-05-01&rft.volume=21&rft.issue=17-18&rft.spage=1983&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2FS0264-410X%2802%2900809-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0264-410X(02)00809-5 ER - TY - JOUR T1 - Systems Toxicology and the Chemical Effects in Biological Systems (CEBS) Knowledge Base AN - 18828654; 5718965 AB - The National Center for Toxicogenomics is developing the first public toxicogenomics knowledge base that combines molecular expression data sets from transcriptomics, proteomics, metabonomics, and conventional toxicology with metabolic, toxicological pathway, and gene regulatory network information relevant to environmental toxicology and human disease. It is called the Chemical Effects in Biological Systems (CEBS) knowledge base and is designed to meet the information needs of "systems toxicology," involving the study of perturbation by chemicals and stressors, monitoring changes in molecular expression and conventional toxicological parameters, and iteratively integrating biological response data to describe the functioning organism. Based upon functional genomics approaches used successfully in analyzing yeast gene expression data sets, relational and descriptive compendia will be assembled for toxicologically important genes, groups of genes, single nucleotide polymorphisms (SNPs), and mutant and knockout phenotypes. CEBS data sets will be fully documented in the experimental protocol and therefore searchable by compound, structure, toxicity end point, pathology end point, gene, gene group, SNP, pathway, and network as a function of dose, time, and the phenotype of the target tissue. A knowledge base is being developed by assimilating toxicological, biological, and chemical information from multiple public domain databases and by progressively refining that information about gene, protein, and metabolite expression for classes of chemicals and their biological effects in various species. By analogy to the GenBank database for genome sequences, researchers will globally query (or BLAST) CEBS using a transcriptome of a tissue of interest (or list of outliers) to have the knowledge base return information on genes, groups of genes, metabolic and toxicological pathways, and contextually associated phenotypic information for compounds that display similar response profiles. With high-quality data content, CEBS will ultimately become a resource to support hypothesis-driven and discovery research that contributes effectively to drug safety and the improvement of risk assessments for chemicals in the environment. The CEBS development effort will span a decade or more. JF - Environmental Health Perspectives AU - Waters, M AU - Boorman, G AU - Bushel, P AU - Cunningham, M AU - Irwin, R AU - Merrick, A AU - Olden, K AU - Paules, R AU - Selkirk, J AU - Stasiewicz, S AU - Weis, B AU - Van Houten, B AU - Walker, N AU - Tennant, R AD - NIEHS, PO Box 12233, MD F1-05, 111 Alexander Drive, Research Triangle Park, NC 27709, USA, waters2@niehs.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 811 EP - 824 VL - 111 IS - 6 SN - 0091-6765, 0091-6765 KW - toxicogenomics KW - Toxicology Abstracts KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18828654?accountid=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=Systems+Toxicology+and+the+Chemical+Effects+in+Biological+Systems+%28CEBS%29+Knowledge+Base&rft.au=Waters%2C+M%3BBoorman%2C+G%3BBushel%2C+P%3BCunningham%2C+M%3BIrwin%2C+R%3BMerrick%2C+A%3BOlden%2C+K%3BPaules%2C+R%3BSelkirk%2C+J%3BStasiewicz%2C+S%3BWeis%2C+B%3BVan+Houten%2C+B%3BWalker%2C+N%3BTennant%2C+R&rft.aulast=Waters&rft.aufirst=M&rft.date=2003-05-01&rft.volume=111&rft.issue=6&rft.spage=811&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Ftxg.5971 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1289/txg.5971 ER - TY - JOUR T1 - The Human Proteome Organization (HUPO) and Environmental Health AN - 18826224; 5718963 AB - The Human Proteome Organization, or HUPO, was formed to promote research and large-scale analysis of the human proteome. By consolidating national proteome organizations into an international body, HUPO will coordinate international initiatives, biological resources, protocols, standards and data for studying the human proteome. HUPO has identified five key areas to advance study of the human proteome, specifically in bioinformatics, new technologies, the plasma proteome, cell models, and a public antibody initiative. Consideration of three major issue areas may help develop HUPO's strategy for human proteome study. First is the need to distinguish the value of high throughput platforms from discovery platforms in proteomics. Second is the importance for international planning on integrating both transcriptome and proteome data and databases. Last is that effects of the environment from chemical, physical, and biological exposures alter the expression and structure of the proteome, which become manifest in long-term adverse health effects and disease. Environmental health research stands to greatly benefit from the shared resources, data, and vision of the HUPO organization as a valuable resource in exploiting knowledge of the human proteome toward improving public health. JF - Environmental Health Perspectives AU - Alex Merrick, B AD - NIEHS, D2-04, PO Box 12233, Research Triangle Park, NC 27709, USA, merrick@niehs.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 797 EP - 801 VL - 111 IS - 6 SN - 0091-6765, 0091-6765 KW - human KW - human Proteome Organization KW - proteomes KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18826224?accountid=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=Environmental+Health+Perspectives&rft.atitle=The+Human+Proteome+Organization+%28HUPO%29+and+Environmental+Health&rft.au=Alex+Merrick%2C+B&rft.aulast=Alex+Merrick&rft.aufirst=B&rft.date=2003-05-01&rft.volume=111&rft.issue=6&rft.spage=797&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Ftxg.5918 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1289/txg.5918 ER - TY - JOUR T1 - Novel Method for Continuous Cell Separation by Density Gradient Centrifugation: Evaluation of a Miniature Separation Column AN - 18804724; 5661382 AB - A compact bench-top model of the centrifuge enables continuous cell separation based on density differences. The apparatus holds a small separation disk equipped with a circular channel (8 mL capacity) separated by a septum. A set of isotonic Percoll media with different densities is continuously introduced at one terminal and collected from the other. Under a centrifugal force field, cell suspension introduced into the proximal portion of the channel results in continuous separation of cells according to their densities. The performance of the apparatus was demonstrated with the separation of human buffy coat containing nucleated cells (>10 super(8)) among a large population (10 super(10)) of RBC. The results indicated that the method is capable of separating a large number of nucleated cells, with minimum damage, for a few hours of operation wherein neutrophils are well resolved from lymphocytes. The method may be applied to other types of samples including cord blood, blood from small animals, cultured cells, pancreatic beta cell islets, malaria parasites, sperm cells, etc. JF - Preparative Biochemistry and Biotechnology AU - Shiono, Hiroyuki AU - Ito, Yoichiro AD - Laboratory of Biophysical Chemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg. 50, Room 3334, 50 South Drive MSC 8014, Bethesda, MD 20892 8014, USA, itoy@nhlbi.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 87 EP - 100 VL - 33 IS - 2 SN - 1082-6068, 1082-6068 KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - W2 32250:Others KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18804724?accountid=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=Preparative+Biochemistry+and+Biotechnology&rft.atitle=Novel+Method+for+Continuous+Cell+Separation+by+Density+Gradient+Centrifugation%3A+Evaluation+of+a+Miniature+Separation+Column&rft.au=Shiono%2C+Hiroyuki%3BIto%2C+Yoichiro&rft.aulast=Shiono&rft.aufirst=Hiroyuki&rft.date=2003-05-01&rft.volume=33&rft.issue=2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Preparative+Biochemistry+and+Biotechnology&rft.issn=10826068&rft_id=info:doi/10.1081%2FPB-120021434 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1081/PB-120021434 ER - TY - JOUR T1 - Experimental Infection of Ixodes scapularis Larvae (Acari: Ixodidae) by Immersion in Low Passage Cultures of Borrelia burgdorferi AN - 18784928; 5660261 AB - We describe a procedure for the introduction of Borrelia burgdorferi , the spirochetal agent of Lyme disease, into larvae of the tick vector Ixodes scapularis . Internalized spirochetes were observed in larvae examined after 15 or 45 min immersion at 32 degree C in liquid culture suspensions of low passage B. burgdorferi strain B31. Larval ticks immersed in low passage strain B31 were able to feed to repletion on white-footed mice. Midguts of larvae contained many spirochetes 1 wk postengorgement, while larvae incubated with high passage strain B31 were free of detectable spirochetes at the same interval. Larvae incubated with low passage strain B31 were competent to transmit the pathogen to mice, as shown by serology, reisolation of B. burgdorferi from mice, and xenodiagnosis. Ticks maintained the infection transstadially to the nymphal stage and transmitted the infection to naive mice, replicating an essential aspect of natural infection. This method requires no special equipment and allows artificial infection of large numbers of ticks at the larval stage. It will facilitate studies of the contribution of specific B. burgdorferi genetic loci to tick colonization. JF - Journal of Medical Entomology AU - Policastro, P F AU - Schwan, T G Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 364 EP - 370 PB - Entomological Society of America VL - 40 IS - 3 SN - 0022-2585, 0022-2585 KW - Acari KW - Deer tick KW - Ixodidae KW - White-footed mouse KW - larvae KW - nymphs KW - Microbiology Abstracts B: Bacteriology; Entomology Abstracts KW - J 02870:Invertebrate bacteriology KW - Z 05206:Medical & veterinary entomology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18784928?accountid=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+Medical+Entomology&rft.atitle=Experimental+Infection+of+Ixodes+scapularis+Larvae+%28Acari%3A+Ixodidae%29+by+Immersion+in+Low+Passage+Cultures+of+Borrelia+burgdorferi&rft.au=Policastro%2C+P+F%3BSchwan%2C+T+G&rft.aulast=Policastro&rft.aufirst=P&rft.date=2003-05-01&rft.volume=40&rft.issue=3&rft.spage=364&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medical+Entomology&rft.issn=00222585&rft_id=info:doi/10.1043%2F0022-2585%282003%29040%280364%3AEIOISL%292.0.CO%3B2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1043/0022-2585(2003)040(0364:EIOISL)2.0.CO;2 ER - TY - JOUR T1 - Stimulation of tumor-reactive T lymphocytes using mixtures of synthetic peptides derived from tumor-associated antigens with diverse MHC binding affinities AN - 18774734; 5643362 AB - The use of reverse immunology may be necessary to identify new tumor-associated antigens, particularly for cancers, against which tumor-reactive T cell populations have been difficult to establish. One approach has been to screen peptides derived from a candidate antigen with high major histocompatibility complex (MHC) binding affinities for the induction of tumor-reactive T lymphocytes in vitro. However, many candidate antigens that are overexpressed in tumors are nonmutated self-proteins, and unlike foreign or mutated proteins, immunodominant epitopes may not be expressed at high density on the surface of tumor cells. Therefore, to identify tumor-associated epitopes, it may be necessary to screen large panels of peptides with wide ranges of MHC binding affinities. The current methodology of stimulating peripheral blood lymphocytes (PBL) from donors expressing the MHC molecule of interest with individual peptides is impractical for screening such large panels. Therefore, we evaluated the use of mixtures of peptides with variable MHC binding affinities for the induction of tumor-reactive T lymphocytes with the melanoma antigens gp100 and an alternate isoform of tyrosinase-related protein 2 (TRP2-6b) as models. A mixture of 10 known human leukocyte antigen (HLA)-A*0201-restricted peptides from gp100 induced melanoma-reactive cytotoxic T lymphoycte (CTL) from multiple patients with metastatic melanoma. The majority of these T cell populations recognized the known immunodominant epitopes gp100:209-217 and gp100:280-288, even though the HLA-A*0201 binding affinities of these peptides were much lower than other peptides in the mixture. Similarly, melanoma-reactive CTL were generated with a mixture of HLA-A*0201-restricted peptides from TRP2-6b, and these responses were directed against the previously identified tumor-associated epitopes TRP2-6b:180-188, TRP2-6b:288-296 and TRP2-6b:403-411. These results suggest that the use of peptide mixtures may facilitate the identification of new tumor-associated antigens through the application of reverse immunology. JF - Journal of Immunological Methods AU - Riley, J P AU - Rosenberg, SA AU - Parkhurst, M R AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Room 2B42, Building 10, 9000 Rockville Pike, Bethesda, MD 20892-1502, USA, Maria_Parkhurst@nih.gov Y1 - 2003/05/01/ PY - 2003 DA - 2003 May 01 SP - 103 EP - 119 VL - 276 IS - 1-2 SN - 0022-1759, 0022-1759 KW - man KW - tyrosinase-related protein 2 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18774734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Stimulation+of+tumor-reactive+T+lymphocytes+using+mixtures+of+synthetic+peptides+derived+from+tumor-associated+antigens+with+diverse+MHC+binding+affinities&rft.au=Riley%2C+J+P%3BRosenberg%2C+SA%3BParkhurst%2C+M+R&rft.aulast=Riley&rft.aufirst=J&rft.date=2003-05-01&rft.volume=276&rft.issue=1-2&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/10.1016%2FS0022-1759%2803%2900078-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0022-1759(03)00078-4 ER - TY - JOUR T1 - The use of PET and knockout mice in the drug discovery process AN - 18770046; 5643148 AB - Although [ super(15)O]H2O, 2-[ super(18)F]fluoro-2-deoxyglucose (FDG) and other radioligands for low-density receptors and enzymes have been used in drug discovery and drug development, the impact on the pharmaceutical industry, to date, has been anecdotal. As new chemical entities are developed, radiotracers that aid in characterizing these drugs need to be developed rapidly to have an impact on the development process. The combined use of positron emission tomography (PET) and gene-manipulated animal models to validate radioligands quickly holds great promise for accelerating the discovery process JF - Drug Discovery Today AU - Eckelman, W C AD - Warren G. Magnuson Clinical Center, National Institutes of Health, 10 Center Drive, 1C495, Bethesda, MD 20892, USA Y1 - 2003/05/01/ PY - 2003 DA - 2003 May 01 SP - 404 EP - 410 PB - Elsevier Science Ltd VL - 8 IS - 9 SN - 1359-6446, 1359-6446 KW - fluoro-2-deoxyglucose KW - knockout mice KW - ligands KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18770046?accountid=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=Drug+Discovery+Today&rft.atitle=The+use+of+PET+and+knockout+mice+in+the+drug+discovery+process&rft.au=Eckelman%2C+W+C&rft.aulast=Eckelman&rft.aufirst=W&rft.date=2003-05-01&rft.volume=8&rft.issue=9&rft.spage=404&rft.isbn=&rft.btitle=&rft.title=Drug+Discovery+Today&rft.issn=13596446&rft_id=info:doi/10.1016%2FS1359-6446%2803%2902678-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S1359-6446(03)02678-3 ER - TY - JOUR T1 - Small non-coding RNAs, co-ordinators of adaptation processes in Escherichia coli : the RpoS paradigm AN - 18767313; 5641235 AB - Adaptation to the changing environment requires both the integration of external signals and the co-ordination of internal responses. Around 50 non-coding small RNAs (sRNAs) have been described in Escherichia coli; the levels of many of these vary with changing environmental conditions. This suggests that they play a role in cell adaptation. In this review, we use the regulation of RpoS ( sigma super(38)) translation as a paradigm of sRNA-mediated response to environmental conditions; rpoS is currently the only known gene regulated post-transcriptionally by at least three sRNAs. DsrA and RprA stimulate RpoS translation in response to low temperature and cell surface stress, respectively, whereas OxyS represses RpoS translation in response to oxidative shock. However, in addition to regulating RpoS translation, DsrA represses the translation of HNS (a global regulator of gene expression), whereas OxyS represses the translation of FhlA (a transcriptional activator), allowing the cell to co-ordinate different pathways involved in cell adaptation. Environmental cues affect the synthesis and stability of specific sRNAs, resulting in specific sRNA-dependent translational control. JF - Molecular Microbiology AU - Repoila, F AU - Majdalani, N AU - Gottesman, S AD - UMR960 INRA - ENVT, Laboratoire de Microbiologie Moleculaire, 23 Chemin des Capelles, 31076 Toulouse Cedex, France., susang@helix.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 855 EP - 861 PB - Blackwell Science Ltd VL - 48 IS - 4 SN - 0950-382X, 0950-382X KW - FhlA protein KW - HNS protein KW - OxyS protein KW - RpoS protein KW - sigma 38 Factor KW - sigma 38 factor KW - sRNA KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02726:RNA and ribosomes KW - N 14100:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18767313?accountid=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=Small+non-coding+RNAs%2C+co-ordinators+of+adaptation+processes+in+Escherichia+coli+%3A+the+RpoS+paradigm&rft.au=Repoila%2C+F%3BMajdalani%2C+N%3BGottesman%2C+S&rft.aulast=Repoila&rft.aufirst=F&rft.date=2003-05-01&rft.volume=48&rft.issue=4&rft.spage=855&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2003.03454.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2003.03454.x ER - TY - JOUR T1 - Chlamydia trachomatis type III secretion: evidence for a functional apparatus during early-cycle development AN - 18762106; 5631000 AB - The obligate intracellular bacterium Chlamydia trachomatis occupies a parasitophorous vacuole termed an inclusion. During its intracellular developmental cycle, C. trachomatis maintains this intracellular niche, presumably by expressing a type III secretion system, which deploys a set of host cell-interactive proteins including inclusion membrane-localized proteins termed Incs. Some Incs are expressed and secreted by 2 h (early cycle) after infection, whereas the expression of type III-specific genes is not detectable until 6-12 h (mid-cycle). To resolve this paradox, we investigated the presence of a type III apparatus on elementary bodies (EBs) that might function early in infection. We demonstrate the existence of the type III secretory apparatus by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) and immunoblot analyses of purified EB extracts. Immunoblots using polyclonal antibodies specific for the core apparatus component CdsJ identified this protein in both EB and reticulate body (RB) extracts. Furthermore, CdsJ-specific signals were detected by immunoblot of whole infected-culture extracts and by indirect immunofluorescence of infected monolayers at times before the detection of cdsJ-specific message. Finally, expression of IncC, expressed by 2 h after infection during C. trachomatis infections, in Yersinia pseudotuberculosis resulted in its secretion via the Yersinia type III apparatus. Based on these data, we propose a model in which type III secretion pores are present on EBs and mediate secretion of early Incs and possible additional effectors. Mid-cycle expression of type III genes would then replenish secretion apparatus on vegetative RBs and serve as a source of secretion pores for subsequently formed EBs. JF - Molecular Microbiology AU - Fields, KA AU - Mead, D J AU - Dooley, CA AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, National Institutes of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840, USA., Ted_Hackstadt@NIH.GOV Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 671 EP - 683 PB - Blackwell Science Ltd VL - 48 IS - 3 SN - 0950-382X, 0950-382X KW - CdsJ protein KW - IncC protein KW - elementary bodies KW - type III secretion KW - Microbiology Abstracts B: Bacteriology KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18762106?accountid=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=Chlamydia+trachomatis+type+III+secretion%3A+evidence+for+a+functional+apparatus+during+early-cycle+development&rft.au=Fields%2C+KA%3BMead%2C+D+J%3BDooley%2C+CA%3BHackstadt%2C+T&rft.aulast=Fields&rft.aufirst=KA&rft.date=2003-05-01&rft.volume=48&rft.issue=3&rft.spage=671&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1046%2Fj.1365-2958.2003.03462.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1046/j.1365-2958.2003.03462.x ER - TY - JOUR T1 - The Escherichia coli Fis Protein Stimulates Bacteriophage lambda Integrative Recombination In Vitro AN - 18745910; 5618699 AB - The Escherichia coli nucleoid-associated protein Fis was previously shown to be involved in bacteriophage lambda site-specific recombination in vivo, enhancing the levels of both integrative recombination and excisive recombination. While purified Fis protein was shown to stimulate in vitro excision, Fis appeared to have no effect on in vitro integration reactions even though a 15-fold drop in lysogenization frequency had previously been observed in fis mutants. We demonstrate here that E. coli Fis protein does stimulate integrative lambda recombination in vitro but only under specific conditions which likely mimic natural in vivo recombination more closely than the standard conditions used in vitro. In the presence of suboptimal concentrations of Int protein, Fis stimulates the rate of integrative recombination significantly. In addition, Fis enhances the recombination of substrates with nonstandard topologies which may be more relevant to the process of in vivo phage lambda recombination. These data support the hypothesis that Fis may play an essential role in lambda recombination in the host cell. JF - Journal of Bacteriology AU - Esposito, D AU - Gerard, G F AD - Protein Expression Laboratory, SAIC-Frederick, Inc., NCI-Frederick, Bldg. 325, P.O. Box B, Frederick, MD 21702, domespo@ncifcrf.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 3076 EP - 3080 VL - 185 IS - 10 SN - 0021-9193, 0021-9193 KW - Fis gene KW - Fis protein KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02750:Phage-host interactions KW - V 22070:Phage-host interactions including lysogeny & transduction KW - N 14551:Virus & phage infections UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18745910?accountid=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+Escherichia+coli+Fis+Protein+Stimulates+Bacteriophage+lambda+Integrative+Recombination+In+Vitro&rft.au=Esposito%2C+D%3BGerard%2C+G+F&rft.aulast=Esposito&rft.aufirst=D&rft.date=2003-05-01&rft.volume=185&rft.issue=10&rft.spage=3076&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.185.10.3076-3080.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.185.10.3076-3080.2003 ER - TY - JOUR T1 - Conservation of Plasmid Maintenance Functions between Linear and Circular Plasmids in Borrelia burgdorferi AN - 18743406; 5618700 AB - The Lyme disease agent Borrelia burgdorferi maintains both linear and circular plasmids that appear to be essential for mammalian infection. Recent studies have characterized the circular plasmid regions that confer autonomous replication, but the genetic elements necessary for linear plasmid maintenance have not been experimentally identified. Two vectors derived from linear plasmids lp25 and lp28-1 were constructed and shown to replicate autonomously in B. burgdorferi. These vectors identify internal regions of linear plasmids necessary for autonomous replication in B. burgdorferi. Although derived from linear plasmids, the vectors are maintained in circular form in B. burgdorferi, indicating that plasmid maintenance functions are conserved, regardless of DNA form. Finally, derivatives of these vectors indicate that paralogous gene family 49 is apparently not required for either circular or linear plasmid replication. JF - Journal of Bacteriology AU - Stewart, P E AU - Chaconas, G AU - Rosa, P AD - Rocky Mountain Laboratories, NIAID, NIH, 903 South 4th St., Hamilton, MT 59840, pestewart@niaid.nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 3202 EP - 3209 VL - 185 IS - 10 SN - 0021-9193, 0021-9193 KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - J 02855:Human Bacteriology: Others KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18743406?accountid=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=Conservation+of+Plasmid+Maintenance+Functions+between+Linear+and+Circular+Plasmids+in+Borrelia+burgdorferi&rft.au=Stewart%2C+P+E%3BChaconas%2C+G%3BRosa%2C+P&rft.aulast=Stewart&rft.aufirst=P&rft.date=2003-05-01&rft.volume=185&rft.issue=10&rft.spage=3202&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/10.1128%2FJB.185.10.3202-3209.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JB.185.10.3202-3209.2003 ER - TY - JOUR T1 - Effect of methanol feeding strategies on production and yield of recombinant mouse endostatin from Pichia pastoris AN - 18700180; 5590037 AB - Pichia pastoris, a methylotrophic yeast, is an efficient producer of recombinant proteins in which the heterologous gene is under the control of the methanol-induced AOX1 promoter. Hence, the accepted production procedure has two phases: In the first phase, the yeast utilizes glycerol and biomass is accumulated; in the second phase, the yeast utilizes methanol which is used both as an inducer for the expression of the recombinant protein and as a carbon source. Since the yeast is sensitive to methanol concentration, the methanol is supplied gradually to the growing culture. Three methanol addition strategies were evaluated for the purpose of optimizing recombinant endostatin production. Two strategies were based on the yeast metabolism; one responding to the methanol consumption using a methanol sensor, and the other responding to the oxygen consumption. In these two strategies, the methanol supply is unlimited. The third strategy was based on a predetermined exponential feeding rate, controling the growth rate at 0.02 h super(-1), in this strategy the methanol supply is limited. Throughout the induction phase glycerol, in addition to methanol, was continuously added at a rate of 1 g L h super(-1). Total endostatin production was similar in all three strategies, (400 mg was obtained from 3 L initial volume), but the amount of methanol added and the biomass produced were lower in the predetermined rate method. This caused the specific production of endostatin per biomass and per methanol to be 2 times higher in the predetermined rate than in the other two methods, making the growth control strategy not only more efficient but also more convenient for downstream processing. JF - Biotechnology and Bioengineering AU - Trinh, L B AU - Phue, J N AU - Shiloach, J AD - Biotechnology Unit, National Institutes of Health, NIDDK Building 6, Room B1-33, Bethesda, Maryland 20892-2715, yossi@nih.gov Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 438 EP - 444 VL - 82 IS - 4 SN - 0006-3592, 0006-3592 KW - AOX1 gene KW - endostatin KW - methanol KW - mice KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Agricultural and Environmental Biotechnology Abstracts KW - A 01116:Bacteria KW - W2 32580:Fermentation and process engineering KW - W 30965:Miscellaneous, Reviews KW - W4 320:Cell Culture & Batch Fermentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18700180?accountid=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+and+Bioengineering&rft.atitle=Effect+of+methanol+feeding+strategies+on+production+and+yield+of+recombinant+mouse+endostatin+from+Pichia+pastoris&rft.au=Trinh%2C+L+B%3BPhue%2C+J+N%3BShiloach%2C+J&rft.aulast=Trinh&rft.aufirst=L&rft.date=2003-05-01&rft.volume=82&rft.issue=4&rft.spage=438&rft.isbn=&rft.btitle=&rft.title=Biotechnology+and+Bioengineering&rft.issn=00063592&rft_id=info:doi/10.1002%2Fbit.10587 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/bit.10587 ER - TY - JOUR T1 - Genetic variation in immune function and susceptibility to human filariasis AN - 1257724122; 16579459 AB - The generation of a draft sequence of a the human genome has provided the opportunity to characterize human diversity, even as it pertains to differences in host response to parasitic infection with organisms that cause lymphatic filariasis, malaria and schistosomiasis. Worldwide, human infection with filarial pathogens represents a significant cause of morbidity throughout the tropics. In particular, epidemiologic evidence suggests that a genetic component contributes to susceptibility and possibly the outcomes of filarial infection. Different approaches can be applied in population-based studies in areas where filarial infection is endemic, such as genome linkage scans and candidate gene analysis for the purpose of identifying genetic risk factors. This review summarizes recent advances in our understanding of genetic contributions to human lymphatic filariasis and addresses the immediate questions facing the field. It is anticipated that the identification of susceptibility genes in filarial infection could provide new insights into therapeutic strategies, including pharmacological intervention and vaccine development, and influence public health measures to control or avert infection. JF - Expert Review of Molecular Diagnostics AU - Choi, Eun Hwa AU - Nutman, Thomas B AU - Chanock, Stephen J AD - Section of Genomic Variation, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Gaithersburg, MD 20892-4605 USA. Y1 - 2003/05// PY - 2003 DA - May 2003 SP - 367 EP - 374 PB - Future Science Group (FSG), Unitec House, 2 Albert Place London N3 1QB United Kingdom VL - 3 IS - 3 SN - 1473-7159, 1473-7159 KW - Genetics Abstracts; ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Immunology Abstracts KW - genetic association studies KW - genetic susceptibility KW - HLA KW - complex KW - host response KW - linkage analysis KW - lymphatic filariasis KW - Genomes KW - Nucleotide sequence KW - Filariasis KW - Disease control KW - Genetic diversity KW - Malaria KW - Hosts KW - Infection KW - Morbidity KW - Public health KW - Endemic species KW - Schistosoma KW - Risk factors KW - Population studies KW - Schistosomiasis KW - Pathogens KW - Reviews KW - Immune response KW - Vaccines KW - G 07880:Human Genetics KW - F 06905:Vaccines KW - Q1 08484:Species interactions: parasites and diseases KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1257724122?accountid=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=Expert+Review+of+Molecular+Diagnostics&rft.atitle=Genetic+variation+in+immune+function+and+susceptibility+to+human+filariasis&rft.au=Choi%2C+Eun+Hwa%3BNutman%2C+Thomas+B%3BChanock%2C+Stephen+J&rft.aulast=Choi&rft.aufirst=Eun&rft.date=2003-05-01&rft.volume=3&rft.issue=3&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Expert+Review+of+Molecular+Diagnostics&rft.issn=14737159&rft_id=info:doi/10.1586%2F14737159.3.3.367 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-12-01 N1 - Last updated - 2015-10-28 N1 - SubjectsTermNotLitGenreText - Genomes; Endemic species; Nucleotide sequence; Disease control; Schistosomiasis; Hosts; Vaccines; Pathogens; Public health; Filariasis; Genetic diversity; Population studies; Malaria; Infection; Morbidity; Reviews; Risk factors; Immune response; Schistosoma DO - http://dx.doi.org/10.1586/14737159.3.3.367 ER - TY - JOUR T1 - Evidence for preferential mismatch repair of lagging strand DNA replication errors in yeast. AN - 73260222; 12725731 AB - Duplex DNA is replicated in the 5'-3' direction by coordinated copying of leading and lagging strand templates with somewhat different proteins and mechanics, providing the potential for differences in the fidelity of replication of the two strands. We previously showed that in Saccharomyces cerevisiae, active replication origins establish a strand bias in the rate of base substitutions resulting from replication of unrepaired 8-oxo-guanine (GO) in DNA. Lower mutagenesis was associated with replicating lagging strand templates. Here, we test the hypothesis that this bias is due to more efficient repair of lagging stand mismatches by measuring mutation rates in ogg1 strains with a reporter allele in two orientations at loci on opposite sides of a replication origin on chromosome III. We compare a MMR-proficient strain to strains deleted for the MMR genes MSH2, MSH6, MLH1, or EXOI. Loss of MMR reduces the strand bias by preferentially increasing mutagenesis for lagging strand replication. We conclude that GO-A mismatches generated during lagging strand replication are more efficiently repaired. This is consistent with the hypothesis that 5' ends of Okazaki fragments and PCNA, present at high density during lagging strand replication, are used as strand discrimination signals for mismatch repair in vivo. JF - Current biology : CB AU - Pavlov, Youri I AU - Mian, Ibrahim M AU - Kunkel, Thomas A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Department of Health and Human Services, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2003/04/29/ PY - 2003 DA - 2003 Apr 29 SP - 744 EP - 748 VL - 13 IS - 9 SN - 0960-9822, 0960-9822 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - 8-hydroxyguanine KW - 5614-64-2 KW - Guanine KW - 5Z93L87A1R KW - DNA Glycosylases KW - EC 3.2.2.- KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - DNA Mutational Analysis KW - Cell Line, Transformed KW - DNA Repair -- genetics KW - DNA-Binding Proteins -- genetics KW - DNA Glycosylases -- genetics KW - Guanine -- analogs & derivatives KW - Base Pair Mismatch -- genetics KW - Guanine -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73260222?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+biology+%3A+CB&rft.atitle=Evidence+for+preferential+mismatch+repair+of+lagging+strand+DNA+replication+errors+in+yeast.&rft.au=Pavlov%2C+Youri+I%3BMian%2C+Ibrahim+M%3BKunkel%2C+Thomas+A&rft.aulast=Pavlov&rft.aufirst=Youri&rft.date=2003-04-29&rft.volume=13&rft.issue=9&rft.spage=744&rft.isbn=&rft.btitle=&rft.title=Current+biology+%3A+CB&rft.issn=09609822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-05 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Low-dose radiation: thresholds, bystander effects, and adaptive responses. AN - 73239064; 12704228 JF - Proceedings of the National Academy of Sciences of the United States of America AU - Bonner, William M AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 5050A, MSC 4255, 9000 Rockville Pike, Bethesda, MD 20892, USA. wmbonner@helix.nih.gov Y1 - 2003/04/29/ PY - 2003 DA - 2003 Apr 29 SP - 4973 EP - 4975 VL - 100 IS - 9 SN - 0027-8424, 0027-8424 KW - Histones KW - 0 KW - Interleukin-8 KW - Index Medicus KW - Animals KW - DNA Repair KW - Phosphorylation KW - DNA Damage KW - Histones -- metabolism KW - Mice, Inbred C3H KW - Mice KW - Dose-Response Relationship, Radiation KW - Interleukin-8 -- metabolism KW - Cell Line KW - Bystander Effect KW - Adaptation, Physiological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73239064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Low-dose+radiation%3A+thresholds%2C+bystander+effects%2C+and+adaptive+responses.&rft.au=Bonner%2C+William+M&rft.aulast=Bonner&rft.aufirst=William&rft.date=2003-04-29&rft.volume=100&rft.issue=9&rft.spage=4973&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 - 2003-06-11 N1 - Date created - 2003-04-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int J Radiat Biol. 1994 Nov;66(5):427-32 [7983426] Radiat Res. 1994 Apr;138(1 Suppl):S28-31 [8146320] Radiat Res. 1996 Oct;146(4):369-73 [8927708] Radiat Res. 1998 Mar;149(3):256-62 [9496888] J Biol Chem. 1998 Mar 6;273(10):5858-68 [9488723] Radiat Res. 1999 Jul;152(1):57-63 [10381841] Radiat Res. 1999 Sep;152(3):273-9 [10453088] J Cell Biol. 1999 Sep 6;146(5):905-16 [10477747] Radiat Res. 1996 Mar;145(3):260-7 [8927692] Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):103-8 [10618378] Biochemistry. 2000 Jul 11;39(27):8026-31 [10891084] Int J Radiat Biol. 2000 Jul;76(7):939-53 [10923618] Curr Biol. 2000 Jul 27-Aug 10;10(15):886-95 [10959836] Science. 2000 Dec 8;290(5498):1962-5 [11110662] Radiat Res. 2001 Mar;155(3):397-401 [11182789] Nat Genet. 2001 Mar;27(3):271-6 [11242108] Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):473-8 [11149936] Radiat Res. 2001 Jun;155(6):759-67 [11352757] Radiat Res. 2001 Aug;156(2):177-80 [11448238] Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14410-5 [11734643] Nature. 2001 Dec 6;414(6864):660-5 [11740565] Curr Opin Genet Dev. 2002 Apr;12(2):162-9 [11893489] Science. 2002 May 3;296(5569):922-7 [11934988] Radiat Res. 2002 Oct;158(4):486-92 [12236816] Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5057-62 [12679524] Science. 1984 Feb 10;223(4636):594-7 [6695170] Nucleic Acids Res. 1989 Nov 25;17(22):9113-26 [2587254] Radiat Res. 1990 Feb;121(2):180-6 [2305036] Cancer Res. 1992 Nov 15;52(22):6394-6 [1423287] Int J Radiat Biol. 1994 Jan;65(1):27-33 [7905906] Comment On: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5057-62 [12679524] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Semiquinone radical intermediate in catecholic estrogen-mediated cytotoxicity and mutagenesis: chemoprevention strategies with antioxidants. AN - 73230181; 12702779 AB - Modulation of the cytotoxicity and mutagenicity of 4-hydroxyestradiol (4-OHE(2)), an oxidative metabolite of estrogen, by antioxidants was assessed in human MCF7 cells and TK-6 lymphoblast cells. The cytotoxicity of the catecholic estrogens was potentiated by depletion of intracellular glutathione and was independent of oxygen concentration. Agents such as the nitroxide Tempol can facilitate the oxidation of the semiquinone to the Q and enhanced 4-OHE(2) cytotoxicity. Conversely, reducing agents such as ascorbate, cysteine, and 1,4-dihydroxytetramethylpiperidine (THP) protected against cytotoxicity and decreased mutation induction, presumably by reducing the semiquinone to the hydroquinone. Our results support the proposition that oxidation of the semiquinone to the corresponding Q is crucial in eliciting the deleterious effects of catecholic estrogens. Furthermore, because the deleterious effects of 4-OHE(2) were abrogated by dietary and synthetic antioxidants, our results would support the chemopreventive use of diets rich in reducing substances (vitamins and added synthetic antioxidants) as a means of decreasing the risks associated with estrogen exposure and developing of breast cancer. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Samuni, Ayelet M AU - Chuang, Eric Y AU - Krishna, Murali C AU - Stein, William AU - DeGraff, William AU - Russo, Angelo AU - Mitchell, James B AD - Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room B3-B69, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2003/04/29/ PY - 2003 DA - 2003 Apr 29 SP - 5390 EP - 5395 VL - 100 IS - 9 SN - 0027-8424, 0027-8424 KW - Antioxidants KW - 0 KW - Estrogens, Catechol KW - Free Radicals KW - Quinones KW - Index Medicus KW - Humans KW - Electron Spin Resonance Spectroscopy KW - Cell Line KW - Antioxidants -- metabolism KW - Estrogens, Catechol -- metabolism KW - Quinones -- metabolism KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73230181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Semiquinone+radical+intermediate+in+catecholic+estrogen-mediated+cytotoxicity+and+mutagenesis%3A+chemoprevention+strategies+with+antioxidants.&rft.au=Samuni%2C+Ayelet+M%3BChuang%2C+Eric+Y%3BKrishna%2C+Murali+C%3BStein%2C+William%3BDeGraff%2C+William%3BRusso%2C+Angelo%3BMitchell%2C+James+B&rft.aulast=Samuni&rft.aufirst=Ayelet&rft.date=2003-04-29&rft.volume=100&rft.issue=9&rft.spage=5390&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 - 2003-06-11 N1 - Date created - 2003-04-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 2000 Jan 15;60(2):235-7 [10667565] Cancer Res. 1999 Jul 1;59(13):3073-6 [10397247] J Natl Cancer Inst Monogr. 2000;(27):67-73 [10963620] J Natl Cancer Inst Monogr. 2000;(27):95-112 [10963622] N Engl J Med. 2001 Jan 25;344(4):276-85 [11172156] Free Radic Biol Med. 2001 Jan 15;30(2):170-7 [11163534] Ann N Y Acad Sci. 2002 Mar;955:48-59; discussion 86-8, 396-406 [11949965] Cell Mol Life Sci. 2002 Apr;59(4):665-81 [12022473] Mol Cell Biochem. 2002 May-Jun;234-235(1-2):327-33 [12162451] Anal Biochem. 1969 Mar;27(3):502-22 [4388022] J Biol Chem. 1972 May 25;247(10):3170-5 [4623845] Anal Biochem. 1976 May 7;72:248-54 [942051] J Biol Chem. 1979 Aug 25;254(16):7558-60 [38242] Anal Biochem. 1981 Jan 1;110(1):1-8 [7011090] Radiat Res. 1985 Aug;103(2):232-9 [4023177] Environ Health Perspect. 1985 Dec;64:185-98 [3007089] Eur J Cancer Clin Oncol. 1988 Jan;24(1):29-43 [3276531] Arch Biochem Biophys. 1988 Oct;266(1):277-84 [2845864] Free Radic Biol Med. 1990;8(4):415-23 [2199344] Cancer Res. 1991 Dec 15;51(24):6622-8 [1660344] Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5537-41 [1319064] Chem Res Toxicol. 1994 Jan-Feb;7(1):23-8 [8155821] Cancer Res. 1994 Nov 1;54(21):5515-7 [7923187] Biochem Pharmacol. 1994 Oct 7;48(7):1427-35 [7945443] J Steroid Biochem Mol Biol. 1994 Dec;51(5-6):251-8 [7826886] Ann N Y Acad Sci. 1995 Sep 30;768:91-100 [8526389] Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3294-6 [8622931] Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2557-63 [8637913] Sci Am. 1996 Sep;275(3):62-70 [8701295] Eur J Cancer Prev. 1997 Feb;6(1):3-10 [9161806] Environ Health Perspect. 1997 Apr;105 Suppl 3:619-24 [9168005] Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10937-42 [9380738] Carcinogenesis. 1998 Jan;19(1):1-27 [9472688] Carcinogenesis. 1998 Jul;19(7):1307-12 [9683193] J Natl Cancer Inst. 1999 Mar 17;91(6):547-56 [10088626] Int J Cancer. 2000 Apr 15;86(2):151-4 [10738239] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Group B streptococcal phospholipid causes pulmonary hypertension AN - 18739409; 5617385 AB - Group B Streptococcus is the most common cause of bacterial infection in the newborn. Infection in many cases causes persistent pulmonary hypertension, which impairs gas exchange in the lung. We purified the bacterial components causing pulmonary hypertension and identified them as cardiolipin and phosphatidylglycerol. Synthetic cardiolipin or phosphatidylglycerol also induced pulmonary hypertension in lambs. The recognition that bacterial phospholipids may cause pulmonary hypertension in newborns with Group B streptococcal infection opens new avenues for therapeutic intervention. JF - Proceedings of the National Academy of Sciences, USA AU - Curtis, J AU - Kim, G AU - Wehr, N B AU - Levine, R L AD - National Naval Medical Center and Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, rlevine@nih.gov Y1 - 2003/04/29/ PY - 2003 DA - 2003 Apr 29 SP - 5087 EP - 5090 VL - 100 IS - 9 SN - 0027-8424, 0027-8424 KW - cardiolipin KW - group B streptococci KW - lambs KW - phosphatidylglycerol KW - pulmonary hypertension KW - sheep KW - Microbiology Abstracts B: Bacteriology KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18739409?accountid=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=Group+B+streptococcal+phospholipid+causes+pulmonary+hypertension&rft.au=Curtis%2C+J%3BKim%2C+G%3BWehr%2C+N+B%3BLevine%2C+R+L&rft.aulast=Curtis&rft.aufirst=J&rft.date=2003-04-29&rft.volume=100&rft.issue=9&rft.spage=5087&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.0931493100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.0931493100 ER - TY - JOUR T1 - Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease. AN - 73230286; 12705907 AB - Recent experimental data suggest that the idiosyncratic nature of drug-induced liver disease (DILD) may be due in part to a deficiency of one or more hepatoprotective factors. In this study we have investigated whether interleukin (IL)-6 may also be one of these factors. Following the induction of liver injury with acetaminophen (APAP), a time-dependent increase in liver mRNA expression of IL-6 and its family members IL-11, leukemia inhibitory factor, and oncostatin M was observed in wild type (WT) mice, suggesting a possible hepatoprotective role played by this cytokine family. Indeed, mice lacking IL-6 (IL-6-/-) were more susceptible than were WT mice to APAP-induced liver injury. The increased susceptibility of the IL-6-/- mice was associated with a deficiency in the expression of hepatic heat shock protein (HSP)25, 32, and 40 as well as inducible HSP70 following APAP treatment. These results suggest that IL-6 and possibly other family members may protect the liver from injury, at least in part, by up-regulating the hepatic expression of several cytoprotective HSPs. JF - Biochemical and biophysical research communications AU - Masubuchi, Yasuhiro AU - Bourdi, Mohammed AU - Reilly, Timothy P AU - Graf, Mary Louise M AU - George, John W AU - Pohl, Lance R AD - Molecular and Cellular Toxicology Section, Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, DHHS, Building 10, Room 8N110, Bethesda, MD 20892-1760, USA. Y1 - 2003/04/25/ PY - 2003 DA - 2003 Apr 25 SP - 207 EP - 212 VL - 304 IS - 1 SN - 0006-291X, 0006-291X KW - Heat-Shock Proteins KW - 0 KW - Inflammation Mediators KW - Interleukin-6 KW - RNA, Messenger KW - Acetaminophen KW - 362O9ITL9D KW - Index Medicus KW - Animals KW - Cytoprotection KW - Gene Expression KW - Mice KW - RNA, Messenger -- biosynthesis KW - Inflammation Mediators -- metabolism KW - Liver Diseases -- metabolism KW - Mice, Knockout KW - Kinetics KW - Mice, Inbred C57BL KW - Liver Diseases -- genetics KW - Male KW - Heat-Shock Proteins -- metabolism KW - Interleukin-6 -- physiology KW - Chemical and Drug Induced Liver Injury KW - Interleukin-6 -- genetics KW - Liver -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73230286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+interleukin-6+in+hepatic+heat+shock+protein+expression+and+protection+against+acetaminophen-induced+liver+disease.&rft.au=Masubuchi%2C+Yasuhiro%3BBourdi%2C+Mohammed%3BReilly%2C+Timothy+P%3BGraf%2C+Mary+Louise+M%3BGeorge%2C+John+W%3BPohl%2C+Lance+R&rft.aulast=Masubuchi&rft.aufirst=Yasuhiro&rft.date=2003-04-25&rft.volume=304&rft.issue=1&rft.spage=207&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 - 2003-05-20 N1 - Date created - 2003-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Naturally occurring amino acid substitutions in the HIV-2 ROD envelope glycoprotein regulate its ability to augment viral particle release. AN - 73228603; 12726729 AB - The envelope glycoprotein of HIV-2 ROD10 has the intriguing ability to enhance the rate of viral particle release from infected cells. However, not all HIV-2 envelope glycoproteins are active in this regard. Indeed, we have previously noted that, despite a high degree of identity with that of ROD10, the envelope protein of the ROD14 isolate was unable to enhance virus production. In this study, site-directed mutagenesis was employed to reveal that a single naturally occurring alanine-to-threonine substitution at position 598, located in the extracellular part of the TM subunit, fully accounted for the lack of activity of the ROD14 Env in HeLa and 12D7 cells. A second mutation at position 422, substituting a lysine residue in ROD10 for an arginine in ROD14, was additionally required for efficient virus release from infected H9 cells, suggesting cell-type-specific requirements for this activity. Interestingly, the ROD14 Env protein exhibited a trans-dominant negative effect on particle release by ROD10 Env, suggesting that the viral release activity of the HIV-2 ROD envelope protein may be regulated by its ability to assemble into functional oligomeric structures. JF - Virology AU - Bour, Stephan AU - Akari, Hirofumi AU - Miyagi, Eri AU - Strebel, Klaus AD - Viral Biochemistry Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA. sbour@niaid.nih.gov Y1 - 2003/04/25/ PY - 2003 DA - 2003 Apr 25 SP - 85 EP - 98 VL - 309 IS - 1 SN - 0042-6822, 0042-6822 KW - Gene Products, env KW - 0 KW - Recombinant Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - HeLa Cells KW - Kinetics KW - Humans KW - Restriction Mapping KW - Amino Acid Substitution KW - Cloning, Molecular KW - Gene Products, env -- physiology KW - Virus Replication -- physiology KW - HIV-2 -- physiology KW - Gene Products, env -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73228603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Naturally+occurring+amino+acid+substitutions+in+the+HIV-2+ROD+envelope+glycoprotein+regulate+its+ability+to+augment+viral+particle+release.&rft.au=Bour%2C+Stephan%3BAkari%2C+Hirofumi%3BMiyagi%2C+Eri%3BStrebel%2C+Klaus&rft.aulast=Bour&rft.aufirst=Stephan&rft.date=2003-04-25&rft.volume=309&rft.issue=1&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-10 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduced endocytosis and altered lysosome function in cisplatin-resistant cell lines. AN - 73189999; 12698203 AB - We isolated human KB adenocarcinoma cisplatin-resistant (CP-r) cell lines with multidrug-resistance phenotypes because of reduced accumulation of cisplatin and other cytotoxic compounds such as methotrexate and heavy metals. The uptake of horseradish peroxidase (HRPO) and Texas Red dextran was decreased several-fold in KB-CP-r cells, indicating a general defect in fluid-phase endocytosis. In contrast, although EGF receptors were decreased in amount, the kinetics of EGF uptake, a marker of receptor-mediated endocytosis, was similar in sensitive and resistant cells. However, 40-60% of the (125)I-EGF released into the medium after uptake into lysosomes of KB-CP-r cells was TCA precipitable as compared to only 10% released by sensitive cells. These results indicate inefficient degradation of internalised (125)I-EGF in the lysosomes of KB-CP-r cells, consistent with slower processing of cathepsin L, a lysosomal cysteine protease. Treatment of KB cells by bafilomycin A(1), a known inhibitor of the vacuolar proton pump, mimicked the phenotype seen in KB-CP-r cells with reduced uptake of HRPO, (125)I-EGF, (14)C-carboplatin, and release of TCA precipitable (125)I-EGF. KB-CP-r cells also had less acidic lysosomes. KB-CP-r cells were crossresistant to Pseudomonas exotoxin, and Pseudomonas exotoxin-resistant KB cells were crossresistant to cisplatin. Since cells with endosomal acidification defects are known to be resistant to Pseudomonas exotoxin and blocking of endosomal acidification mimics the CP-r phenotype, we conclude that defective endosomal acidification may contribute to acquired cisplatin resistance. JF - British journal of cancer AU - Chauhan, S S AU - Liang, X J AU - Su, A W AU - Pai-Panandiker, A AU - Shen, D W AU - Hanover, J A AU - Gottesman, M M AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20842-4254, USA. Y1 - 2003/04/22/ PY - 2003 DA - 2003 Apr 22 SP - 1327 EP - 1334 VL - 88 IS - 8 SN - 0007-0920, 0007-0920 KW - Epidermal Growth Factor KW - 62229-50-9 KW - Carboplatin KW - BG3F62OND5 KW - Horseradish Peroxidase KW - EC 1.11.1.- KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Horseradish Peroxidase -- pharmacokinetics KW - Humans KW - Biological Transport KW - Drug Resistance, Neoplasm KW - Carcinoma, Squamous Cell KW - Epidermal Growth Factor -- metabolism KW - Carboplatin -- pharmacokinetics KW - Lysosomes -- physiology KW - Cell Line, Tumor -- physiology KW - Cisplatin -- toxicity KW - Endocytosis -- drug effects KW - Cell Line, Tumor -- ultrastructure KW - Lysosomes -- drug effects KW - Endocytosis -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73189999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reduced+endocytosis+and+altered+lysosome+function+in+cisplatin-resistant+cell+lines.&rft.au=Chauhan%2C+S+S%3BLiang%2C+X+J%3BSu%2C+A+W%3BPai-Panandiker%2C+A%3BShen%2C+D+W%3BHanover%2C+J+A%3BGottesman%2C+M+M&rft.aulast=Chauhan&rft.aufirst=S&rft.date=2003-04-22&rft.volume=88&rft.issue=8&rft.spage=1327&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 - 2004-11-16 N1 - Date created - 2003-04-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7690-4 [7644478] Cancer Res. 1995 Feb 1;55(3):474-7 [7834610] Blood. 1995 Sep 1;86(5):1903-10 [7655019] Oncol Res. 1995;7(1):31-8 [7549042] Pharmacotherapy. 1996 Jan-Feb;16(1):16-39 [8700790] Oncol Res. 1995;7(7-8):363-9 [8747599] Exp Cell Res. 1996 Jul 10;226(1):133-9 [8660948] Blood. 1997 Aug 1;90(3):1208-16 [9242554] Int J Hyperthermia. 1997 Sep-Oct;13(5):439-57 [9354931] Cancer Res. 1998 Jan 15;58(2):268-75 [9443404] Cancer Res. 1998 Mar 15;58(6):1120-3 [9515792] Clin Cancer Res. 1998 Jan;4(1):1-6 [9516945] Biochemistry. 1998 Jun 9;37(23):8584-94 [9622510] Nature. 1998 Jul 9;394(6689):192-5 [9671304] Eur J Cancer. 1998 Sep;34(10):1535-42 [9893624] Br J Cancer. 1995 Apr;71(4):676-83 [7710928] Biochem Pharmacol. 2000 Feb 15;59(4):337-45 [10644041] J Cell Physiol. 2000 Apr;183(1):108-16 [10699972] Int J Cancer. 2001 Sep15;93(6):869-74 [11519050] Mol Pharmacol. 2001 Dec;60(6):1153-60 [11723219] Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14298-302 [12370430] Cancer Res. 2002 Nov 15;62(22):6559-65 [12438251] J Cell Biol. 1976 Oct;71(1):159-71 [977646] Cancer Res. 1987 Jun 1;47(11):2961-6 [3494506] J Natl Cancer Inst. 1988 Mar 2;80(1):14-20 [2892943] J Cell Physiol. 1988 Jun;135(3):502-8 [3294236] Science. 1988 Sep 30;241(4874):1813-5 [3175622] Cancer Res. 1989 May 15;49(10):2761-5 [2713859] Curr Probl Cancer. 1989 Sep-Oct;13(5):285-335 [2551577] J Cell Biol. 1989 Dec;109(6 Pt 1):2731-9 [2556406] Cancer Treat Res. 1988;37:39-73 [2908634] Biochem J. 1990 Nov 15;272(1):39-44 [2264836] J Biol Chem. 1991 Sep 15;266(26):17707-12 [1832676] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3070-4 [1348364] Annu Rev Biochem. 1992;61:331-54 [1497314] Mol Cell Biol. 1992 Sep;12(9):3689-98 [1380646] Nature. 1992 Oct 8;359(6395):554-6 [1406976] Cancer Res. 1992 Nov 15;52(22):6188-93 [1423261] Br J Cancer. 1992 Dec;66(6):1109-15 [1457352] Cell. 1993 Sep 24;74(6):957-67 [8402885] J Biol Chem. 1994 Jan 14;269(2):787-90 [8288625] Cancer Res. 1994 Dec 15;54(24):6464-8 [7987844] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DnaE2 polymerase contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis. AN - 73219441; 12705867 AB - The presence of multiple copies of the major replicative DNA polymerase (DnaE) in some organisms, including important pathogens and symbionts, has remained an unresolved enigma. We postulated that one copy might participate in error-prone DNA repair synthesis. We found that UV irradiation of Mycobacterium tuberculosis results in increased mutation frequency in the surviving fraction. We identified dnaE2 as a gene that is upregulated in vitro by several DNA damaging agents, as well as during infection of mice. Loss of this protein reduces both survival of the bacillus after UV irradiation and the virulence of the organism in mice. Our data suggest that DnaE2, and not a member of the Y family of error-prone DNA polymerases, is the primary mediator of survival through inducible mutagenesis and can contribute directly to the emergence of drug resistance in vivo. These results may indicate a potential new target for therapeutic intervention. JF - Cell AU - Boshoff, Helena I M AU - Reed, Michael B AU - Barry, Clifton E AU - Mizrahi, Valerie AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II, 12441 Parklawn Drive, Rockville, MD 20852, USA. Y1 - 2003/04/18/ PY - 2003 DA - 2003 Apr 18 SP - 183 EP - 193 VL - 113 IS - 2 SN - 0092-8674, 0092-8674 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Animals KW - DNA Replication -- genetics KW - Gene Expression Regulation, Enzymologic -- genetics KW - Genome, Bacterial KW - Cell Survival -- genetics KW - Humans KW - Mice KW - DNA Damage -- genetics KW - Gene Expression Regulation, Bacterial -- genetics KW - Tuberculosis, Multidrug-Resistant -- enzymology KW - Drug Resistance -- genetics KW - Mycobacterium tuberculosis -- enzymology KW - Tuberculosis, Multidrug-Resistant -- genetics KW - Mycobacterium tuberculosis -- genetics KW - Mutation -- genetics KW - DNA-Directed DNA Polymerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73219441?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DnaE2+polymerase+contributes+to+in+vivo+survival+and+the+emergence+of+drug+resistance+in+Mycobacterium+tuberculosis.&rft.au=Boshoff%2C+Helena+I+M%3BReed%2C+Michael+B%3BBarry%2C+Clifton+E%3BMizrahi%2C+Valerie&rft.aulast=Boshoff&rft.aufirst=Helena+I&rft.date=2003-04-18&rft.volume=113&rft.issue=2&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-16 N1 - Date created - 2003-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystal structure of an alpha 1,4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis. AN - 73176478; 12562774 AB - EXTL2, an alpha1,4-N-acetylhexosaminyltransferase, catalyzes the transfer reaction of N-acetylglucosamine and N-acetylgalactosamine from the respective UDP-sugars to the non-reducing end of [glucuronic acid]beta1-3[galactose]beta1-O-naphthalenemethanol, an acceptor substrate analog of the natural common linker of various glycosylaminoglycans. We have solved the x-ray crystal structure of the catalytic domain of mouse EXTL2 in the apo-form and with donor substrates UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine. In addition, a structure of the ternary complex with UDP and the acceptor substrate analog [glucuronic acid]beta1-3[galactose]beta1-O-naphthalenemethanol has been determined. These structures reveal three highly conserved residues, Asn-243, Asp-246, and Arg-293, located at the active site. Mutation of these residues greatly decreases the activity. In the ternary complex, an interaction exists between the beta-phosphate of the UDP leaving group and the acceptor hydroxyl of the substrate that may play a functional role in catalysis. These structures represent the first structures from the exostosin gene family and provide important insight into the mechanisms of alpha1,4-N-acetylhexosaminyl transfer in heparan biosynthesis. JF - The Journal of biological chemistry AU - Pedersen, Lars C AU - Dong, Jian AU - Taniguchi, Fumiyasu AU - Kitagawa, Hiroshi AU - Krahn, Joe M AU - Pedersen, Lee G AU - Sugahara, Kazuyuki AU - Negishi, Masahiko AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/04/18/ PY - 2003 DA - 2003 Apr 18 SP - 14420 EP - 14428 VL - 278 IS - 16 SN - 0021-9258, 0021-9258 KW - Membrane Proteins KW - 0 KW - Aspartic Acid KW - 30KYC7MIAI KW - Uridine Diphosphate N-Acetylglucosamine KW - 528-04-1 KW - Asparagine KW - 7006-34-0 KW - Heparitin Sulfate KW - 9050-30-0 KW - Arginine KW - 94ZLA3W45F KW - EXTL2 protein, human KW - EC 2.4.1.- KW - N-Acetylgalactosaminyltransferases KW - N-Acetylglucosaminyltransferases KW - UDP-N-acetylgalactosamine (GlcUA-GalNAc-4-sulfate)(4) N-acetylgalactosaminyltransferase KW - Index Medicus KW - Animals KW - COS Cells KW - Arginine -- chemistry KW - Models, Molecular KW - Catalytic Domain KW - Amino Acid Sequence KW - Mice KW - Uridine Diphosphate N-Acetylglucosamine -- metabolism KW - Aspartic Acid -- chemistry KW - Binding Sites KW - Mutagenesis, Site-Directed KW - N-Acetylgalactosaminyltransferases -- metabolism KW - Transfection KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Hydrogen Bonding KW - Asparagine -- chemistry KW - Protein Conformation KW - Heparitin Sulfate -- chemistry KW - N-Acetylglucosaminyltransferases -- chemistry KW - Heparitin Sulfate -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73176478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Crystal+structure+of+an+alpha+1%2C4-N-acetylhexosaminyltransferase+%28EXTL2%29%2C+a+member+of+the+exostosin+gene+family+involved+in+heparan+sulfate+biosynthesis.&rft.au=Pedersen%2C+Lars+C%3BDong%2C+Jian%3BTaniguchi%2C+Fumiyasu%3BKitagawa%2C+Hiroshi%3BKrahn%2C+Joe+M%3BPedersen%2C+Lee+G%3BSugahara%2C+Kazuyuki%3BNegishi%2C+Masahiko&rft.aulast=Pedersen&rft.aufirst=Lars&rft.date=2003-04-18&rft.volume=278&rft.issue=16&rft.spage=14420&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 - 2003-05-22 N1 - Date created - 2003-04-14 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1ON6; PDB; 1OMX; 1ON8; 1OMZ N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exposure to lead in children--how low is low enough? AN - 73212991; 12700370 JF - The New England journal of medicine AU - Rogan, Walter J AU - Ware, James H AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Y1 - 2003/04/17/ PY - 2003 DA - 2003 Apr 17 SP - 1515 EP - 1516 VL - 348 IS - 16 KW - Lead KW - 2P299V784P KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Lead Poisoning -- complications KW - Child KW - Adolescent KW - Female KW - Child, Preschool KW - Lead -- adverse effects KW - Intelligence -- drug effects KW - Puberty -- drug effects KW - Environmental Exposure -- standards KW - Environmental Exposure -- adverse effects KW - Lead -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73212991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Exposure+to+lead+in+children--how+low+is+low+enough%3F&rft.au=Rogan%2C+Walter+J%3BWare%2C+James+H&rft.aulast=Rogan&rft.aufirst=Walter&rft.date=2003-04-17&rft.volume=348&rft.issue=16&rft.spage=1515&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=1533-4406&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-23 N1 - Date created - 2003-04-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: N Engl J Med. 2003 Apr 17;348(16):1517-26 [12700371] N Engl J Med. 2003 Apr 17;348(16):1527-36 [12700372] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener's granulomatosis: extended follow-up and rate of relapse. AN - 73252940; 12727579 AB - To determine the relapse rate and outcome in patients with Wegener's granulomatosis treated with daily cyclophosphamide and glucocorticoids to induce remission followed by methotrexate for remission maintenance. We performed an open-label prospective study in 42 patients with active Wegener's granulomatosis. All patients were treated with a standardized regimen. Outcomes were assessed using predetermined definitions based on clinical characteristics and pathologic, laboratory, and radiographic findings. All patients achieved disease remission. The median time to remission was 3 months, and the median time to discontinuation of glucocorticoids was 8 months. During a median of 32 months of follow-up, 1 patient died (of a myocardial infarction not related to vasculitis). Two patients (5%) had to withdraw from the study because of medication toxicity. Twenty-two patients (52%) relapsed, with glomerulonephritis occurring in 16 patients. Of these 16 patients, 4 had an increase of >0.2 mg/dL in serum creatinine level. All 4 patients returned to their prior level of renal function with treatment. None of the 22 relapses met the criteria for severe disease. The use of cyclophosphamide and glucocorticoids for induction and methotrexate for maintaining remission is an effective and well-tolerated therapeutic approach in patients with active Wegener's granulomatosis. JF - The American journal of medicine AU - Langford, Carol A AU - Talar-Williams, Cheryl AU - Barron, Karyl S AU - Sneller, Michael C AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. clangford@niaid.nih.gov Y1 - 2003/04/15/ PY - 2003 DA - 2003 Apr 15 SP - 463 EP - 469 VL - 114 IS - 6 SN - 0002-9343, 0002-9343 KW - Antibodies, Antineutrophil Cytoplasmic KW - 0 KW - Antimetabolites, Antineoplastic KW - Antineoplastic Agents, Alkylating KW - Glucocorticoids KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Prednisone -- therapeutic use KW - Aged KW - Child KW - Recurrence KW - Antibodies, Antineutrophil Cytoplasmic -- analysis KW - Prospective Studies KW - Adult KW - Follow-Up Studies KW - Glucocorticoids -- therapeutic use KW - Adolescent KW - Female KW - Male KW - Remission Induction KW - Granulomatosis with Polyangiitis -- immunology KW - Antineoplastic Agents, Alkylating -- therapeutic use KW - Cyclophosphamide -- therapeutic use KW - Methotrexate -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects KW - Methotrexate -- therapeutic use KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Granulomatosis with Polyangiitis -- drug therapy KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73252940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+medicine&rft.atitle=Use+of+a+cyclophosphamide-induction+methotrexate-maintenance+regimen+for+the+treatment+of+Wegener%27s+granulomatosis%3A+extended+follow-up+and+rate+of+relapse.&rft.au=Langford%2C+Carol+A%3BTalar-Williams%2C+Cheryl%3BBarron%2C+Karyl+S%3BSneller%2C+Michael+C&rft.aulast=Langford&rft.aufirst=Carol&rft.date=2003-04-15&rft.volume=114&rft.issue=6&rft.spage=463&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+medicine&rft.issn=00029343&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-13 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calorie restriction and diet composition modulate spontaneous intestinal tumorigenesis in Apc(Min) mice through different mechanisms. AN - 73207577; 12702556 AB - We evaluated the effects of diet on intestinal tumorigenesis in male Apc(Min) mice by comparing AIN-76A diet fed ad libitum (CON); calorie intake restricted by 40% of the CON (CR); diet high in olive oil and supplemented with freeze-dried fruit and vegetable extracts (OFV); and diet high in total fat (HF). Compared with CON, the frequency of intestinal polyps was reduced by 57% by CR (P < 0.001) and by 33% OFV diet (P = 0.04). Both effective interventions reduced total body weight, lean mass, and fat mass and increased daily urinary corticosterone output, but only CR reduced serum insulin-like growth factor I and leptin. We conclude that dietary interventions can partially offset genetic susceptibility to intestinal carcinogenesis. JF - Cancer research AU - Mai, Volker AU - Colbert, Lisa H AU - Berrigan, David AU - Perkins, Susan N AU - Pfeiffer, Ruth AU - Lavigne, Jackie A AU - Lanza, Elaine AU - Haines, Diana C AU - Schatzkin, Arthur AU - Hursting, Stephen D AD - Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892-7105, USA. Y1 - 2003/04/15/ PY - 2003 DA - 2003 Apr 15 SP - 1752 EP - 1755 VL - 63 IS - 8 SN - 0008-5472, 0008-5472 KW - Leptin KW - 0 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Corticosterone KW - W980KJ009P KW - Index Medicus KW - Body Weight KW - Animals KW - Intestinal Polyps -- prevention & control KW - Corticosterone -- urine KW - Body Composition -- physiology KW - Mice, Inbred C57BL KW - Insulin-Like Growth Factor I -- metabolism KW - Mice KW - Intestinal Polyps -- metabolism KW - Genetic Predisposition to Disease KW - Diet KW - Intestinal Polyps -- genetics KW - Male KW - Leptin -- blood KW - Genes, APC KW - Intestinal Neoplasms -- metabolism KW - Energy Intake KW - Intestinal Neoplasms -- genetics KW - Intestinal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73207577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Calorie+restriction+and+diet+composition+modulate+spontaneous+intestinal+tumorigenesis+in+Apc%28Min%29+mice+through+different+mechanisms.&rft.au=Mai%2C+Volker%3BColbert%2C+Lisa+H%3BBerrigan%2C+David%3BPerkins%2C+Susan+N%3BPfeiffer%2C+Ruth%3BLavigne%2C+Jackie+A%3BLanza%2C+Elaine%3BHaines%2C+Diana+C%3BSchatzkin%2C+Arthur%3BHursting%2C+Stephen+D&rft.aulast=Mai&rft.aufirst=Volker&rft.date=2003-04-15&rft.volume=63&rft.issue=8&rft.spage=1752&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 - 2003-05-16 N1 - Date created - 2003-04-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A photochemical study of cells loaded with 2',7'-dichlorofluorescin: implications for the detection of reactive oxygen species generated during UVA irradiation. AN - 73183602; 12684087 AB - There have been several attempts to implicate reactive oxygen species in UVA-induced damage by loading cells with 2',7'-dichlorofluorescin (DCFH) and following the appearance of 2',7'-dichlorofluorescein (DCF), its highly fluorescent oxidation product. However, both DCF and DCFH have significant absorption in the 300-400 nm range so it is possible that photochemical reactions will occur in cells containing these dyes when they are irradiated with UVA. HaCaT keratinocytes loaded with DCFH were irradiated with 0, 1, 2, or 4 J/cm(2) UVA and DCF fluorescence was measured. A dose-dependent increase in DCF fluorescence was observed, with the cells exposed to 4 J/cm(2) UVA exhibiting an almost 10-fold increase over dark controls. However, there was no difference in cell viability, as measured by the MTS assay or LDH release, between the dark and the 4 J/cm(2) UVA-exposed groups. Furthermore, a large increase in DCF fluorescence was observed when a cell-free system containing DCF, DCFH, and horseradish peroxidase was UVA irradiated. As a control, keratinocytes loaded with DCFH were incubated in the dark with either exogenously added H(2)O(2) or 5-hydroxy-1,4-naphthoquinone (juglone), which redox cycles to generate superoxide (and H(2)O(2)). In both cases, the cells showed a concentration-dependent increase in DCF fluorescence and a concomitant decrease in viability. Our findings suggest that DCFH can not be used to detect the UVA-induced generation of reactive oxygen species in cells when the dye is present during exposure. JF - Free radical biology & medicine AU - Chignell, Colin F AU - Sik, Robert H AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709-2233, USA. chignell@niehs.nih.gov Y1 - 2003/04/15/ PY - 2003 DA - 2003 Apr 15 SP - 1029 EP - 1034 VL - 34 IS - 8 SN - 0891-5849, 0891-5849 KW - Enzyme Inhibitors KW - 0 KW - Fluoresceins KW - Free Radicals KW - Naphthoquinones KW - Reactive Oxygen Species KW - 2',7'-dichlorofluorescein KW - 56NQM5UZT1 KW - Hydrogen Peroxide KW - BBX060AN9V KW - juglone KW - W6Q80SK9L6 KW - Index Medicus KW - Oxidation-Reduction KW - Ultraviolet Rays KW - Humans KW - Naphthoquinones -- pharmacology KW - Hydrogen Peroxide -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Models, Chemical KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Cell Line KW - Photochemistry -- methods KW - Fluoresceins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73183602?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=A+photochemical+study+of+cells+loaded+with+2%27%2C7%27-dichlorofluorescin%3A+implications+for+the+detection+of+reactive+oxygen+species+generated+during+UVA+irradiation.&rft.au=Chignell%2C+Colin+F%3BSik%2C+Robert+H&rft.aulast=Chignell&rft.aufirst=Colin&rft.date=2003-04-15&rft.volume=34&rft.issue=8&rft.spage=1029&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-05 N1 - Date created - 2003-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of peptide mimotopes of lipooligosaccharide from nontypeable Haemophilus influenzae as vaccine candidates. AN - 73172066; 12682274 AB - Nontypeable Haemophilus influenzae (NTHi) is a common cause of otitis media in children and lower respiratory tract diseases in adults. So far there is no effective vaccine against NTHi. A major surface-exposed component of NTHi, lipooligosaccharide (LOS), is a virulence factor as well as a potential protective Ag. LOS is too toxic to be administered in humans. However, detoxified LOS is a T cell-independent small molecule and is poorly immunogenic in vivo, so we converted LOS into a nontoxic T cell-dependent Ag through the use of peptides that mimic the LOS by screening a phage-display peptide library with a rabbit Ab specific for NTHi LOS. Fifty-six phage clones were found to share LOS mimicry molecules. Among them, 22 clones were subjected to DNA sequencing, and four consensus sequences were identified as NMMRFTSQPPNN, NMMNYIMDPRTH, NMMKYISPPIFL, and NMMRFTELSTPS. Three of the four synthetic peptides showed strong binding reactivity to the rabbit anti-LOS Ab and also a mouse bactericidal monoclonal anti-LOS Ab in vitro, and elicited specific serum anti-LOS Abs in rabbits (27- to 81-fold) after conjugation with keyhole limpet hemocyanin. Passive immunization with the rabbit antisera resulted in a significantly enhanced pulmonary bacterial clearance in a mouse model. The enhanced bacterial clearance was eliminated if the rabbit serum was preabsorbed with NTHi LOS. These data indicate that the peptide mimotopes of LOS that we have identified might be potential components of peptide vaccines against NTHi. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Hou, Yingchun AU - Gu, Xin-Xing AD - National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA. Y1 - 2003/04/15/ PY - 2003 DA - 2003 Apr 15 SP - 4373 EP - 4379 VL - 170 IS - 8 SN - 0022-1767, 0022-1767 KW - Antibodies, Bacterial KW - 0 KW - Haemophilus Vaccines KW - Immune Sera KW - Lipopolysaccharides KW - Peptide Fragments KW - Peptide Library KW - Vaccines, Conjugate KW - lipid-linked oligosaccharides KW - Abridged Index Medicus KW - Index Medicus KW - Haemophilus Infections -- immunology KW - Vaccines, Conjugate -- immunology KW - Animals KW - Cloning, Molecular -- methods KW - Rabbits KW - Mice KW - Mice, Inbred BALB C KW - Protein Binding -- immunology KW - Haemophilus Infections -- prevention & control KW - Antibody Specificity KW - Antibodies, Bacterial -- metabolism KW - Bacteriophages -- immunology KW - Immune Sera -- administration & dosage KW - Immunization, Passive KW - Injections, Subcutaneous KW - Vaccines, Conjugate -- chemistry KW - Antibodies, Bacterial -- biosynthesis KW - Binding Sites, Antibody KW - Female KW - Lipopolysaccharides -- chemical synthesis KW - Lipopolysaccharides -- immunology KW - Lipopolysaccharides -- metabolism KW - Molecular Mimicry -- immunology KW - Haemophilus Vaccines -- immunology KW - Haemophilus Vaccines -- chemical synthesis KW - Peptide Fragments -- immunology KW - Peptide Fragments -- chemical synthesis KW - Haemophilus influenzae -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73172066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Development+of+peptide+mimotopes+of+lipooligosaccharide+from+nontypeable+Haemophilus+influenzae+as+vaccine+candidates.&rft.au=Hou%2C+Yingchun%3BGu%2C+Xin-Xing&rft.aulast=Hou&rft.aufirst=Yingchun&rft.date=2003-04-15&rft.volume=170&rft.issue=8&rft.spage=4373&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 - 2003-07-31 N1 - Date created - 2003-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Forum report: issues in the design of trials of drugs for the treatment of invasive aspergillosis. AN - 73170101; 12679894 AB - A recent trial of drugs for invasive aspergillosis was used as a background for discussing critical features in the design of antifungal trials. The study under discussion allowed stopping either drug without classifying the patient as having treatment failure, so the trial should be understood as a comparison of 2 treatment strategies, not just 2 drugs. Although the study was a noninferiority trial, the outcome permitted a claim of superiority. Use of the category of "probable" in addition to "proven" aspergillosis permitted inclusion of patients for whom the diagnosis was less certain but who were still early enough in the disease progression to respond to therapy. Different opinions still exist about some of the criteria for the diagnosis of "probable" aspergillosis. A blinded data review committee was helpful in evaluating efficacy in this unblinded trial but had limited value in assessing toxicity. An understanding of these features of design of antifungal drug trials is important in applying the results to clinical practice. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Bennett, John E AU - Powers, John AU - de Pauw, Ben AU - Dismukes, William AU - Galgiani, John AU - Glauser, Michel AU - Herbrecht, Raoul AU - Kauffman, Carol AU - Lee, Jeannette AU - Pappas, Peter AU - Rex, John AU - Verweij, Paul AU - Viscoli, Claudio AU - Walsh, Thomas AD - Clinical Mycology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jbennett@niaid.nih.gov Y1 - 2003/04/15/ PY - 2003 DA - 2003 Apr 15 SP - S113 EP - S116 VL - 36 KW - Antifungal Agents KW - 0 KW - Index Medicus KW - Biomedical Research KW - Humans KW - Patient Selection KW - Aspergillosis -- diagnosis KW - Aspergillosis -- drug therapy KW - Clinical Trials as Topic KW - Research Design KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73170101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Forum+report%3A+issues+in+the+design+of+trials+of+drugs+for+the+treatment+of+invasive+aspergillosis.&rft.au=Bennett%2C+John+E%3BPowers%2C+John%3Bde+Pauw%2C+Ben%3BDismukes%2C+William%3BGalgiani%2C+John%3BGlauser%2C+Michel%3BHerbrecht%2C+Raoul%3BKauffman%2C+Carol%3BLee%2C+Jeannette%3BPappas%2C+Peter%3BRex%2C+John%3BVerweij%2C+Paul%3BViscoli%2C+Claudio%3BWalsh%2C+Thomas&rft.aulast=Bennett&rft.aufirst=John&rft.date=2003-04-15&rft.volume=36&rft.issue=&rft.spage=S113&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=1537-6591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-22 N1 - Date created - 2003-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide in cancer and chemoprevention. AN - 73161198; 12684081 AB - Nitric oxide (NO) is a key molecule involved in many physiological functions. However, evidence is accumulating that sustained high levels of NO over extended periods of time contribute to carcinogenesis. This article reviews recent data and outlines a dual role of NO in animal carcinogenesis. Following an inhibition of NO production, some studies find a protection, while others find an exacerbation of tumorigenesis. These studies reflect the importance of (i). choosing the appropriate compound for NO inhibition; and (ii). genetic background, target tissue, levels of NO, and surrounding free radicals in the overall affects of NO on the tumor growth. These findings highlight the importance of further study of the use of NO inhibitors to inhibit human carcinogenesis. JF - Free radical biology & medicine AU - Hofseth, Lorne J AU - Hussain, S Perwez AU - Wogan, Gerald N AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/04/15/ PY - 2003 DA - 2003 Apr 15 SP - 955 EP - 968 VL - 34 IS - 8 SN - 0891-5849, 0891-5849 KW - Nitric Oxide KW - 31C4KY9ESH KW - NOS2 protein, human KW - EC 1.14.13.39 KW - Nitric Oxide Synthase KW - Nitric Oxide Synthase Type II KW - Index Medicus KW - Animals KW - Humans KW - Disease Models, Animal KW - Nitric Oxide Synthase -- metabolism KW - Nitric Oxide -- antagonists & inhibitors KW - Nitric Oxide -- metabolism KW - Neoplasms -- prevention & control KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73161198?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Nitric+oxide+in+cancer+and+chemoprevention.&rft.au=Hofseth%2C+Lorne+J%3BHussain%2C+S+Perwez%3BWogan%2C+Gerald+N%3BHarris%2C+Curtis+C&rft.aulast=Hofseth&rft.aufirst=Lorne&rft.date=2003-04-15&rft.volume=34&rft.issue=8&rft.spage=955&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-05 N1 - Date created - 2003-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitochondrial DNA mutations in patients with myelodysplastic syndromes. AN - 73155748; 12446454 AB - We undertook to systematically analyze the entire mitochondrial genome by gene amplification and direct sequencing in 10 patients with myelodysplasia; results were compared with concomitantly studied 8 healthy volunteers as well as mtDNA sequences in a standard database. Nucleotide changes that were present in our healthy controls as well as those in published databases were counted as polymorphisms. Overall, there was no increase in the number of mtDNA genes harboring polymorphisms or "new" mutations between our patients and healthy controls, although there were a few more mtDNA changes resulting in amino acid changes in myelodysplasia (9 in 8 controls versus 16 in 10 patients). Thirty new mutations, all nucleotide substitutions, were found among the 10 patients, distributed throughout the mitochondrial genome; 5 mutations resulted in amino acid changes. None of the mutations in controls produced amino acid changes. We were not able to confirm previously described mutations in sideroblastic anemia or "hot spots" in the cytochrome c oxidase I and II genes. Our data do not support a major role for mitochondrial genomic instability in myelodysplasia, and they fail to reproduce previous reports of significant or widespread mitochondrial mutations in this disease. Modest changes in mutation numbers and mitochondrial microsatellites may be evidence of increased mutagenesis in mtDNA, or, more likely, a reflection of limited clonality among hematopoietic stem cells in this bone marrow failure syndrome. JF - Blood AU - Shin, Myung Geun AU - Kajigaya, Sachiko AU - Levin, Barbara C AU - Young, Neal S AD - Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/04/15/ PY - 2003 DA - 2003 Apr 15 SP - 3118 EP - 3125 VL - 101 IS - 8 SN - 0006-4971, 0006-4971 KW - Cytochrome b Group KW - 0 KW - DNA, Mitochondrial KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Abridged Index Medicus KW - Index Medicus KW - Electron Transport Complex IV -- genetics KW - Cytochrome b Group -- genetics KW - Anemia, Refractory, with Excess of Blasts -- genetics KW - Polymorphism, Genetic KW - Humans KW - DNA Mutational Analysis KW - Adult KW - Point Mutation KW - Aged KW - Middle Aged KW - Mutation, Missense KW - Male KW - Female KW - Bone Marrow Cells -- ultrastructure KW - Amino Acid Substitution KW - Anemia, Refractory -- genetics KW - DNA, Mitochondrial -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73155748?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mitochondrial+DNA+mutations+in+patients+with+myelodysplastic+syndromes.&rft.au=Shin%2C+Myung+Geun%3BKajigaya%2C+Sachiko%3BLevin%2C+Barbara+C%3BYoung%2C+Neal+S&rft.aulast=Shin&rft.aufirst=Myung&rft.date=2003-04-15&rft.volume=101&rft.issue=8&rft.spage=3118&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-18 N1 - Date created - 2003-04-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adrenomedullin and cancer. AN - 73155192; 12667640 AB - Adrenomedullin (AM) is a pluripotent hormone with structural similarities to calcitonin gene-related peptide (CGRP), which is expressed by many tissues in the body and shows a remarkable range of effects mediated by paracrine/autocrine and possibly endocrine mechanisms. AM has been implicated as a mediator of several pathologies such as cardiovascular and renal disorders, sepsis, inflammation, diabetes and cancer, among others. AM is expressed in a variety of tumors where it aggravates several of the molecular and physiological features of malignant cells. AM has been shown to be a mitogenic factor stimulating growth in several cancer types and to encourage a more aggressive tumor phenotype. In addition, AM is an apoptosis survival factor for cancer cells and an indirect suppressor of the immune response through its binding protein, complement factor H, and regulation in expression of cytokines. AM plays an important role in environments subjected to low oxygen tensions, which is a typical feature in the proximity of solid tumors. Under these conditions, AM is upregulated through a hypoxia-inducible factor 1 (HIF-1)-dependent pathway and acts as a potent angiogenic factor promoting neovascularization. The collective findings brought together over the last years place AM as a major regulator of carcinogenesis-tumor progression and identifies its autocrine loop as a putative target for developing new strategies against human cancers. JF - Regulatory peptides AU - Zudaire, E AU - Martínez, A AU - Cuttitta, F AD - Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 13N262, Bethesda MD 20892, USA. zudairee@mail.nih.gov Y1 - 2003/04/15/ PY - 2003 DA - 2003 Apr 15 SP - 175 EP - 183 VL - 112 IS - 1-3 SN - 0167-0115, 0167-0115 KW - Angiogenesis Inducing Agents KW - 0 KW - Peptides KW - Receptors, Adrenomedullin KW - Receptors, Peptide KW - Adrenomedullin KW - 148498-78-6 KW - Index Medicus KW - Rats KW - Immunologic Surveillance KW - Animals KW - Angiogenesis Inducing Agents -- metabolism KW - Receptors, Peptide -- metabolism KW - Apoptosis KW - Humans KW - Cell Hypoxia KW - Signal Transduction KW - Peptides -- physiology KW - Neoplasms -- etiology KW - Neoplasms -- metabolism KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73155192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Regulatory+peptides&rft.atitle=Adrenomedullin+and+cancer.&rft.au=Zudaire%2C+E%3BMart%C3%ADnez%2C+A%3BCuttitta%2C+F&rft.aulast=Zudaire&rft.aufirst=E&rft.date=2003-04-15&rft.volume=112&rft.issue=1-3&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Regulatory+peptides&rft.issn=01670115&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-03-01 N1 - Date created - 2003-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts. AN - 73174140; 12547826 AB - Although epidemiological studies have long established that inorganic arsenic is a potent human carcinogen, the underlying mechanisms are still poorly understood. Recent studies suggest that inorganic arsenic may act as a tumor promoter by perturbing key signaling transduction pathways. We have shown previously that arsenite can potently activate the mitogen-activated protein kinase cascades and induce the expression of proliferation-associated genes, including proto-oncogenes c-jun and c-fos. In order to elucidate further the molecular mechanisms underlying its tumor-promoting properties, we investigated the signaling events involved in arsenite-mediated induction of c-fos and c-jun. We found that induction of both c-fos and c-jun by arsenite can be substantially inhibited by the MEK- selective inhibitor U0126, suggesting that the ERK pathway is critically involved in their up-regulation. Interestingly, arsenite dramatically induced the phosphorylation and acetylation of histone H3 preceding the induction of mRNAs encoding c-fos and c-jun. Finally, chromatin immunoprecipitation assays revealed that arsenite treatment markedly induced the phosphorylation/acetylation of histone H3 associated with the c-fos and c-jun genes through an ERK-dependent pathway. Our results strongly suggest that arsenic-triggered alterations in chromatin structure perturb specific gene transcription, including that of proto-oncogenes c-jun and c-fos, and may thereby contribute to the carcinogenic process. JF - The Journal of biological chemistry AU - Li, Ji AU - Gorospe, Myriam AU - Barnes, Janice AU - Liu, Yusen AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2003/04/11/ PY - 2003 DA - 2003 Apr 11 SP - 13183 EP - 13191 VL - 278 IS - 15 SN - 0021-9258, 0021-9258 KW - Arsenites KW - 0 KW - Butadienes KW - Carcinogens KW - Chromatin KW - DNA Primers KW - Enzyme Inhibitors KW - Histones KW - Nitriles KW - RNA, Messenger KW - U 0126 KW - Phosphoserine KW - 17885-08-4 KW - Ribosomal Protein S6 Kinases, 90-kDa KW - EC 2.7.11.1 KW - mitogen and stress-activated protein kinase 1 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - arsenite KW - N5509X556J KW - Index Medicus KW - Carcinogens -- pharmacology KW - Fibroblasts -- drug effects KW - Nitriles -- pharmacology KW - Humans KW - Transcription, Genetic KW - RNA, Messenger -- genetics KW - Phosphoserine -- metabolism KW - Fibroblasts -- metabolism KW - Polymerase Chain Reaction KW - Acetylation KW - Ribosomal Protein S6 Kinases, 90-kDa -- metabolism KW - Base Sequence KW - Phosphorylation KW - Butadienes -- pharmacology KW - Kinetics KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Ribosomal Protein S6 Kinases, 90-kDa -- antagonists & inhibitors KW - Cell Cycle -- drug effects KW - Diploidy KW - Arsenites -- pharmacology KW - Chromatin -- metabolism KW - Histones -- metabolism KW - Chromatin -- drug effects KW - Genes, fos KW - Genes, jun UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73174140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+promoter+arsenite+stimulates+histone+H3+phosphoacetylation+of+proto-oncogenes+c-fos+and+c-jun+chromatin+in+human+diploid+fibroblasts.&rft.au=Li%2C+Ji%3BGorospe%2C+Myriam%3BBarnes%2C+Janice%3BLiu%2C+Yusen&rft.aulast=Li&rft.aufirst=Ji&rft.date=2003-04-11&rft.volume=278&rft.issue=15&rft.spage=13183&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 - 2003-07-03 N1 - Date created - 2003-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An extracellular calcium-binding domain in bacteria with a distant relationship to EF-hands AN - 18755226; 5623884 AB - Extracellular Ca super(2+)-dependent nuclease YokF from Bacillus subtilis and several other surface-exposed proteins from diverse bacteria are encoded in the genomes in two paralogous forms that differ by a similar to 45 amino acid fragment, which comprises a novel conserved domain. Sequence analysis of this domain revealed a conserved DxDxDGxxCE motif, which is strikingly similar to the Ca super(2+)-binding loop of the calmodulin-like EF-hand domains, suggesting an evolutionary relationship between them. Functions of many of the other proteins in which the novel domain, named Excalibur (extracellular calcium-binding region), is found, as well as a structural model of its conserved motif are consistent with the notion that the Excalibur domain binds calcium. This domain is but one more example of the diversity of structural contexts surrounding the EF-hand-like calcium-binding loop in bacteria. This loop is thus more widespread than hitherto recognized and the evolution of EF-hand-like domains is probably more complex than previously appreciated. JF - FEMS Microbiology Letters AU - Rigden, D J AU - Jedrzejas, MJ AU - Galperin, MY AD - National Center of Genetic Resources and Biotechnology, Cenargen/Embrapa, Brasilia D.F. 70770-900, Brazil, galperin@ncbi.nlm.nih.gov Y1 - 2003/04/11/ PY - 2003 DA - 2003 Apr 11 SP - 103 EP - 110 PB - Federation of European Microbiological Societies VL - 221 IS - 1 SN - 0378-1097, 0378-1097 KW - YokF protein KW - nucleotide sequence KW - Microbiology Abstracts B: Bacteriology KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18755226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=An+extracellular+calcium-binding+domain+in+bacteria+with+a+distant+relationship+to+EF-hands&rft.au=Rigden%2C+D+J%3BJedrzejas%2C+MJ%3BGalperin%2C+MY&rft.aulast=Rigden&rft.aufirst=D&rft.date=2003-04-11&rft.volume=221&rft.issue=1&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/10.1016%2FS0378-1097%2803%2900160-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0378-1097(03)00160-5 ER - TY - JOUR T1 - From Knowing to Controlling: A Path from Genomics to Drugs Using Small Molecule Probes AN - 18730936; 5605158 AB - The National Cancer Institute Initiative in Chemical Genetics is designed to encourage the development of small molecular probes. The probes are useful for activating or inactivating protein functions, thereby providing resources that help discern the functions of gene products in normal and disease cells, as well as in tissues. This initiative includes "ChemBank," a suite of informatics tools and databases aimed at promoting the development and use of chemical genetics by scientists worldwide. The information generated with such tools should provide a critical link from genomic discovery to drug development. JF - Science (Washington) AU - Strausberg, R L AU - Schreiber, S L AD - Cancer Genomics Office, National Cancer Institute, 31 Center Drive, Bethesda, MD 20892, USA, RLS@nih.gov Y1 - 2003/04/11/ PY - 2003 DA - 2003 Apr 11 SP - 294 EP - 295 PB - American Association for the Advancement of Science VL - 300 IS - 5617 SN - 0036-8075, 0036-8075 KW - ChemBank KW - chemical genetics KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - G 07220:General theory/testing systems 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/18730936?accountid=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=Science+%28Washington%29&rft.atitle=From+Knowing+to+Controlling%3A+A+Path+from+Genomics+to+Drugs+Using+Small+Molecule+Probes&rft.au=Strausberg%2C+R+L%3BSchreiber%2C+S+L&rft.aulast=Strausberg&rft.aufirst=R&rft.date=2003-04-11&rft.volume=300&rft.issue=5617&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Early Origin and Recent Expansion of Plasmodium falciparum AN - 18720110; 5605163 AB - The emergence of virulent Plasmodium falciparum in Africa within the past 6000 years as a result of a cascade of changes in human behavior and mosquito transmission has recently been hypothesized. Here, we provide genetic evidence for a sudden increase in the African malaria parasite population about 10,000 years ago, followed by migration to other regions on the basis of variation in 100 worldwide mitochondrial DNA sequences. However, both the world and some regional populations appear to be older (50,000 to 100,000 years old), suggesting an earlier wave of migration out of Africa, perhaps during the Pleistocene migration of human beings. JF - Science (Washington) AU - Joy, DA AU - Feng, X AU - Mu, J AU - Furuya, T AU - Chotivanich, K AU - Krettli, A U AU - Ho, M AU - Wang, A AU - White, N J AU - Suh, E AU - Beerli, P AU - Su, X-Z AD - Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0425, USA, djoy@niaid.nih.gov Y1 - 2003/04/11/ PY - 2003 DA - 2003 Apr 11 SP - 318 EP - 321 PB - American Association for the Advancement of Science VL - 300 IS - 5617 SN - 0036-8075, 0036-8075 KW - Man KW - Mosquitoes KW - Genetics Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Human diseases KW - Protozoan diseases KW - Genetic diversity KW - Malaria KW - Freshwater KW - Virulence KW - Population genetics KW - Homo sapiens KW - Parasitic diseases KW - Biological vectors KW - Genetic variance KW - Subpopulations KW - Culicidae KW - Plasmodium falciparum KW - Pathogens KW - Mitochondrial DNA KW - Migrations KW - DNA KW - Africa KW - Evolution KW - Dispersion KW - Q1 08443:Population genetics KW - Q1 08205:Genetics and evolution KW - Q1 08484:Species interactions: parasites and diseases KW - K 03081:Protozoa KW - Q5 08524:Public health, medicines, dangerous organisms KW - G 07260:Taxonomy, systematics and evolutionary genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18720110?accountid=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=Science+%28Washington%29&rft.atitle=Early+Origin+and+Recent+Expansion+of+Plasmodium+falciparum&rft.au=Joy%2C+DA%3BFeng%2C+X%3BMu%2C+J%3BFuruya%2C+T%3BChotivanich%2C+K%3BKrettli%2C+A+U%3BHo%2C+M%3BWang%2C+A%3BWhite%2C+N+J%3BSuh%2C+E%3BBeerli%2C+P%3BSu%2C+X-Z&rft.aulast=Joy&rft.aufirst=DA&rft.date=2003-04-11&rft.volume=300&rft.issue=5617&rft.spage=318&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-07 N1 - SubjectsTermNotLitGenreText - Biological vectors; Human diseases; Protozoan diseases; Subpopulations; Genetic diversity; Malaria; Pathogens; Virulence; Population genetics; DNA; Migrations; Parasitic diseases; Evolution; Dispersion; Mitochondrial DNA; Genetic variance; Homo sapiens; Culicidae; Plasmodium falciparum; Africa; Freshwater ER - TY - JOUR T1 - Real-time quantitative reverse transcriptase-polymerase chain reaction as a method for determining lentiviral vector titers and measuring transgene expression. AN - 73234147; 12718761 AB - The use of lentiviral vectors for basic research and potential future clinical applications requires methodologies that can accurately determine lentiviral titers and monitor viral transgene expression within target cells, beyond the context of reporter genes typically used for this purpose. Here we describe a quantitative RT-PCR (qRT-PCR) method that achieves both goals using primer sequences that are specific for the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), an enhancer contained in many retroviral vectors and that is incorporated in the 3' UTR of nascent transgene transcripts. Quantitation of titers of three recombinant lentiviruses, genetically identical except for the transgene, demonstrated consistent differences in titer that were likely due to transgene-associated toxicity in producer cells and target cells. Viruses encoding the tumor-associated antigens tyrosinase and neo-poly(A) polymerase yielded reproducibly lower titers than a virus encoding enhanced green fluorescent protein (GFP) at the viral RNA, integrated DNA, and transgene mRNA levels, as measured by WPRE qPCR. Furthermore, the magnitude of differences in expression of the three transgenes in transduced target cells could not have been predicted by measuring vector DNA integration events. Since transgene expression in target cells is the most common goal of lentiviral transduction, and since methods to quantify transgene expression on the protein level are not always readily available, qRT-PCR based on a nucleotide sequence included in the transcript provides a useful tool for titering novel recombinant lentiviruses. JF - Human gene therapy AU - Lizée, Gregory AU - Aerts, Joeri L AU - Gonzales, Monica I AU - Chinnasamy, Nachimuthu AU - Morgan, Richard A AU - Topalian, Suzanne L AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/04/10/ PY - 2003 DA - 2003 Apr 10 SP - 497 EP - 507 VL - 14 IS - 6 SN - 1043-0342, 1043-0342 KW - 3' Untranslated Regions KW - 0 KW - Luminescent Proteins KW - RNA, Messenger KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Index Medicus KW - Virion -- genetics KW - HeLa Cells KW - Humans KW - Transduction, Genetic KW - Gene Expression KW - Hepatitis Viruses -- genetics KW - Luminescent Proteins -- metabolism KW - Genes, Regulator -- genetics KW - Virus Integration KW - RNA, Messenger -- biosynthesis KW - Enhancer Elements, Genetic -- genetics KW - Flow Cytometry KW - Cell Line, Transformed KW - 3' Untranslated Regions -- genetics KW - Luminescent Proteins -- genetics KW - Cell Line KW - Genetic Vectors KW - Transgenes KW - Lentivirus -- genetics KW - Reverse Transcriptase Polymerase Chain Reaction -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73234147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+gene+therapy&rft.atitle=Real-time+quantitative+reverse+transcriptase-polymerase+chain+reaction+as+a+method+for+determining+lentiviral+vector+titers+and+measuring+transgene+expression.&rft.au=Liz%C3%A9e%2C+Gregory%3BAerts%2C+Joeri+L%3BGonzales%2C+Monica+I%3BChinnasamy%2C+Nachimuthu%3BMorgan%2C+Richard+A%3BTopalian%2C+Suzanne+L&rft.aulast=Liz%C3%A9e&rft.aufirst=Gregory&rft.date=2003-04-10&rft.volume=14&rft.issue=6&rft.spage=497&rft.isbn=&rft.btitle=&rft.title=Human+gene+therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-26 N1 - Date created - 2003-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cisplatin-induced cytotoxicity is blocked by brain-derived neurotrophic factor activation of TrkB signal transduction path in neuroblastoma. AN - 73182929; 12691830 AB - We evaluated the ability of brain-derived neurotrophic factor (BDNF) to decrease the chemosensitivity of neuroblastoma cells to cisplatin. Two cell lines, one derived from SH-SY5Y (SY5Y-TB8) and the other from SK-N-AS (AS-TB8), transfected with a TrkB plasmid were generated, and used to assess the effects of activation of the TrkB signal transduction path on cisplatin (Cis) induced apoptosis. BDNF treatment of each of the TrkB expressing cells blocked cisplatin-induced cell death. BDNF's ability to rescue the cells from cisplatin-induced cell death was inhibited by treatment with the Trk tyrosine kinase inhibitor, K252a, and the phosphatidylinositol 3'-kinase (PI)-3-kinase inhibitor, LY294002. This indicates that the activation of the TrkB path through PI-3-kinase is required for BDNF's survival-promoting effects. JF - Cancer letters AU - Jaboin, Jerry AU - Hong, Audrey AU - Kim, Chong Jai AU - Thiele, Carol J AD - Cell and Molecular Biology Section, Pediatric Oncology Branch, Center for Cancer Research, NCI, 10 Center Dr. MSC-1928, Bethesda, MD, USA. Y1 - 2003/04/10/ PY - 2003 DA - 2003 Apr 10 SP - 109 EP - 114 VL - 193 IS - 1 SN - 0304-3835, 0304-3835 KW - Antineoplastic Agents KW - 0 KW - Brain-Derived Neurotrophic Factor KW - Chromones KW - Enzyme Inhibitors KW - Morpholines KW - Recombinant Proteins KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Receptor, trkB KW - EC 2.7.10.1 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Immunoblotting KW - Apoptosis KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Dose-Response Relationship, Drug KW - Enzyme Activation KW - Humans KW - Morpholines -- pharmacology KW - Precipitin Tests KW - Tumor Cells, Cultured KW - Chromones -- pharmacology KW - Transfection KW - Recombinant Proteins -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Brain-Derived Neurotrophic Factor -- metabolism KW - Cisplatin -- toxicity KW - Receptor, trkB -- metabolism KW - Neuroblastoma -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73182929?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cisplatin-induced+cytotoxicity+is+blocked+by+brain-derived+neurotrophic+factor+activation+of+TrkB+signal+transduction+path+in+neuroblastoma.&rft.au=Jaboin%2C+Jerry%3BHong%2C+Audrey%3BKim%2C+Chong+Jai%3BThiele%2C+Carol+J&rft.aulast=Jaboin&rft.aufirst=Jerry&rft.date=2003-04-10&rft.volume=193&rft.issue=1&rft.spage=109&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 - 2003-06-27 N1 - Date created - 2003-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elucidation of the epsilon - theta Subunit Interface of Escherichia coli DNA Polymerase III by NMR Spectroscopy AN - 18814883; 5687722 AB - The DNA polymerase III holoenzyme (HE) is the primary replicative polymerase of Escherichia coli. The epsilon ( epsilon ) subunit of HE provides the 3' arrow right 5' exonucleolytic proofreading activity for this complex. epsilon consists of two domains: an N-terminal domain containing the proofreading exonuclease activity (residues 1-186) and a C-terminal domain required for binding to the polymerase ( alpha ) subunit (residues 187-243). In addition to alpha , epsilon also binds the small (8 kDa) theta ( theta ) subunit. The function of theta is unknown, although it has been hypothesized to enhance the 3' arrow right 5' exonucleolytic proofreading activity of epsilon . Using NMR analysis and molecular modeling, we have previously reported a structural model of epsilon 186, the N-terminal catalytic domain of epsilon [DeRose et al. (2002) Biochemistry 41, 94]. Here, we have performed 3D triple resonance NMR experiments to assign the backbone and C beta resonances of [U- super(2)H, super(13)C, super(15)N] methyl protonated epsilon 186 in complex with unlabeled theta . A structural comparison of the epsilon 186- theta complex with free epsilon 186 revealed no major changes in secondary structure, implying that the overall structure is not significantly perturbed in the complex. Amide chemical shift comparisons between bound and unbound epsilon 186 revealed a potential binding surface on epsilon for interaction with theta involving structural elements near the epsilon catalytic site. The most significant shifts observed for the epsilon 186 amide resonances are localized to helix alpha 1 and beta -strands 2 and 3 and to the region near the beginning of alpha -helix 7. Additionally, a small stretch of residues (K158-L161), which previously had not been assigned in uncomplexed epsilon 186, is predicted to adopt beta -strand secondary structure in the epsilon 186- theta complex and may be significant for interaction with theta . The amide shift pattern was confirmed by the shifts of aliphatic methyl protons, for which the larger shifts generally were concentrated in the same regions of the protein. These chemical shift mapping results also suggest an explanation for how the unstable dnaQ49 mutator phenotype of epsilon may be stabilized by binding theta . JF - Biochemistry (Washington) AU - DeRose, E F AU - Darden, T AU - Harvey, S AU - Gabel, S AU - Perrino, F W AU - Schaaper, R M AU - London, R E AD - Laboratories of Structural Biology and Molecular Genetics, National Institute of Environmental Health Sciences, Box 12233, Research Triangle Park, North Carolina 27709, USA Y1 - 2003/04/08/ PY - 2003 DA - 2003 Apr 08 SP - 3635 EP - 3644 VL - 42 IS - 13 SN - 0006-2960, 0006-2960 KW - molecular modeling KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18814883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Elucidation+of+the+epsilon+-+theta+Subunit+Interface+of+Escherichia+coli+DNA+Polymerase+III+by+NMR+Spectroscopy&rft.au=DeRose%2C+E+F%3BDarden%2C+T%3BHarvey%2C+S%3BGabel%2C+S%3BPerrino%2C+F+W%3BSchaaper%2C+R+M%3BLondon%2C+R+E&rft.aulast=DeRose&rft.aufirst=E&rft.date=2003-04-08&rft.volume=42&rft.issue=13&rft.spage=3635&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi0205451 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1021/bi0205451 ER - TY - JOUR T1 - Current developments in the design of onco-retrovirus and lentivirus vector systems for hematopoietic cell gene therapy. AN - 73151520; 12676350 AB - Over the past dozen years, the majority of clinical gene therapy trials for inherited genetic diseases and cancer therapy have been performed using murine onco-retrovirus as the gene delivery vector. The earliest systems used were relatively inefficient in both the rates of transduction and expression of the transgene. Formidable obstacles inherent in the cell biology and/or the immunology of the target cell systems limited the efficacy of gene therapy for many target diseases. Development of novel retrovirus gene transfer systems that are in progress have begun to overcome these obstacles. Evidence of this progress is the recent successful functional correction of the immune T and B lymphocyte deficiency in patients with X-linked severe combined immunodeficiency (X-SCID) and adenosine deaminase (ADA)-deficient SCID following onco-retrovirus vector ex vivo transduction of autologous marrow stem cells [Science 296 (2002) 2410; Science 288 (2000) 669; N. Engl. J. Med. 346 (2002) 1185]. These achievements of prolonged clinical benefit from gene therapy were tempered by the finding of insertional mutageneses in two of the treated X-SCID patients [N. Engl. J. Med. 348 (2003) 255]. JF - Biochimica et biophysica acta AU - Brenner, Sebastian AU - Malech, Harry L AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. sbrenner@nih.gov Y1 - 2003/04/07/ PY - 2003 DA - 2003 Apr 07 SP - 1 EP - 24 VL - 1640 IS - 1 SN - 0006-3002, 0006-3002 KW - Index Medicus KW - Animals KW - Lentivirus KW - Humans KW - Transduction, Genetic KW - Clinical Trials as Topic KW - Spumavirus KW - Hematopoietic Stem Cells KW - Retroviridae KW - Genetic Vectors -- therapeutic use KW - Genetic Therapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73151520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Current+developments+in+the+design+of+onco-retrovirus+and+lentivirus+vector+systems+for+hematopoietic+cell+gene+therapy.&rft.au=Brenner%2C+Sebastian%3BMalech%2C+Harry+L&rft.aulast=Brenner&rft.aufirst=Sebastian&rft.date=2003-04-07&rft.volume=1640&rft.issue=1&rft.spage=1&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 - 2003-08-21 N1 - Date created - 2003-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development and use of fluorescent protein markers in living cells. AN - 73168608; 12677058 AB - The ability to visualize, track, and quantify molecules and events in living cells with high spatial and temporal resolution is essential for understanding biological systems. Only recently has it become feasible to carry out these tasks due to the advent of fluorescent protein technology. Here, we trace the development of highly visible and minimally perturbing fluorescent proteins that, together with updated fluorescent imaging techniques, are providing unprecedented insights into the movement of proteins and their interactions with cellular components in living cells. JF - Science (New York, N.Y.) AU - Lippincott-Schwartz, Jennifer AU - Patterson, George H AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. jlippin@helix.nih.gov Y1 - 2003/04/04/ PY - 2003 DA - 2003 Apr 04 SP - 87 EP - 91 VL - 300 IS - 5616 KW - Luminescent Proteins KW - 0 KW - Proteins KW - Recombinant Fusion Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Index Medicus KW - Fluorescence Recovery After Photobleaching -- methods KW - Protein Engineering KW - Fluorescence KW - Spectrometry, Fluorescence KW - Fluorometry -- methods KW - Kinetics KW - Light KW - Mutagenesis KW - Microscopy -- methods KW - Cell Physiological Phenomena KW - Microscopy, Fluorescence -- methods KW - Luminescent Proteins -- metabolism KW - Luminescent Proteins -- chemistry KW - Proteins -- metabolism KW - Luminescent Proteins -- genetics KW - Diagnostic Imaging -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73168608?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=Development+and+use+of+fluorescent+protein+markers+in+living+cells.&rft.au=Lippincott-Schwartz%2C+Jennifer%3BPatterson%2C+George+H&rft.aulast=Lippincott-Schwartz&rft.aufirst=Jennifer&rft.date=2003-04-04&rft.volume=300&rft.issue=5616&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=1095-9203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-25 N1 - Date created - 2003-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular determinants of the stereoselectivity of agonist activity of estrogen receptors (ER) alpha and beta. AN - 73141745; 12547836 AB - The two known estrogen receptors, ERalpha and ERbeta, are hormone-inducible transcription factors that have distinct roles in regulating cell proliferation and differentiation. Previously, our laboratory demonstrated that ERalpha exhibits stereoselective ligand binding and transactivation for several structural derivatives and metabolites of the synthetic estrogen diethylstilbestrol. We have previously described the properties of indenestrol A (IA) enantiomers on ERalpha. In the study presented here, the estrogenic properties of the S and R enantiomers of IA, IA-S and IA-R, respectively, were expanded to examine the activity in different cell and promoter contexts using ERalpha and ERbeta. Using human cell lines stably expressing either ERalpha or ERbeta, we found that IA-S was a more potent activator of transcription than IA-R through ERalpha in human endometrial Ishikawa and breast MDA-MB 231 (MDA) cells. Interestingly, IA-R was more potent on ERbeta when compared with ERalpha in MDA, but not in Ishikawa cells, and IA-R exhibited equally low binding affinities to ERalpha and ERbeta in vitro in contrast to its cell line-dependent preferential activation of ERbeta. Alignment of the protein structures of the ligand-binding domains of ERalpha and ERbeta revealed one mismatched residue, Leu-384 in ERalpha and Met-283 in ERbeta, which may be responsible for making contact with the methyl substituent at the chiral carbon of IA-S and IA-R. Mutagenesis and exchange of this one residue showed that the binding of IA-R and IA-S was not affected by this mutation in ERalpha and ERbeta. However, in transactivation studies, IA-R showed higher potency in activating L384M-mutated ERalpha and wild-type ERbeta compared with wild-type ERalpha and M283L-mutated ERbeta in all cell and promoter contexts examined. Furthermore, IA-R-bound ERalpha L384M and wild-type ERbeta displayed enhanced interactions with the nuclear receptor interaction domains of the coactivators SRC-1 and GRIP1. These data demonstrate that a single residue in the ligand-binding domain determines the stereoselectivity of ERalpha and ERbeta for indenestrol ligands and that IA-R shows cell type selectivity through ERbeta. JF - The Journal of biological chemistry AU - Mueller, Stefan O AU - Hall, Julie M AU - Swope, Deborah L AU - Pedersen, Lars C AU - Korach, Kenneth S AD - Laboratories of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. stefan.o.mueller@merck.de Y1 - 2003/04/04/ PY - 2003 DA - 2003 Apr 04 SP - 12255 EP - 12262 VL - 278 IS - 14 SN - 0021-9258, 0021-9258 KW - Estrogen Receptor alpha KW - 0 KW - Estrogen Receptor beta KW - Indenes KW - Receptors, Estrogen KW - indenestrol KW - 4A464K3BSI KW - Estradiol KW - 4TI98Z838E KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Estradiol -- chemistry KW - Humans KW - Diethylstilbestrol -- chemistry KW - Gene Expression KW - Endometrium -- cytology KW - Structure-Activity Relationship KW - Mutagenesis KW - Breast -- cytology KW - Indenes -- chemistry KW - Molecular Conformation KW - Cell Line KW - Female KW - Receptors, Estrogen -- genetics KW - Receptors, Estrogen -- chemistry KW - Receptors, Estrogen -- agonists UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73141745?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Molecular+determinants+of+the+stereoselectivity+of+agonist+activity+of+estrogen+receptors+%28ER%29+alpha+and+beta.&rft.au=Mueller%2C+Stefan+O%3BHall%2C+Julie+M%3BSwope%2C+Deborah+L%3BPedersen%2C+Lars+C%3BKorach%2C+Kenneth+S&rft.aulast=Mueller&rft.aufirst=Stefan&rft.date=2003-04-04&rft.volume=278&rft.issue=14&rft.spage=12255&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 - 2003-05-19 N1 - Date created - 2003-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of helix 1 aspartates and salt bridges in the stability and conversion of prion protein. AN - 73140600; 12551897 AB - A key event in the pathogenesis of transmissible spongiform encephalopathies is the conversion of PrP-sen to PrP-res. Morrissey and Shakhnovich (Morrissey, M. P., and Shakhnovich, E. I. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 11293-11298) proposed that the conversion mechanism involves critical interactions at helix 1 (residues 144-153) and that the helix is stabilized on PrP-sen by intra-helix salt bridges between two aspartic acid-arginine ion pairs at positions 144 and 148 and at 147 and 151, respectively. Mutants of the hamster prion protein were constructed by replacing the aspartic acids with either asparagines or alanines to destabilize the proposed helix 1 salt bridges. Thermal and chemical denaturation experiments using circular dichroism spectroscopy indicated the overall structures of the mutants are not substantially destabilized but appear to unfold differently. Cell-free conversion reactions performed using ionic denaturants, detergents, and salts (conditions unfavorable to salt bridge formation) showed no significant differences between conversion efficiencies of mutant and wild type proteins. Using conditions more favorable to salt bridge formation, the mutant proteins converted with up to 4-fold higher efficiency than the wild type protein. Thus, although spectroscopic data indicate the salt bridges do not substantially stabilize PrP-sen, the cell-free conversion data suggest that Asp-144 and Asp-147 and their respective salt bridges stabilize PrP-sen from converting to PrP-res. JF - The Journal of biological chemistry AU - Speare, Jonathan O AU - Rush, Thomas S AU - Bloom, Marshall E AU - Caughey, Byron AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840, USA. Y1 - 2003/04/04/ PY - 2003 DA - 2003 Apr 04 SP - 12522 EP - 12529 VL - 278 IS - 14 SN - 0021-9258, 0021-9258 KW - Disulfides KW - 0 KW - Prions KW - Salts KW - Aspartic Acid KW - 30KYC7MIAI KW - Guanidine KW - JU58VJ6Y3B KW - Index Medicus KW - Hot Temperature KW - Animals KW - Protein Structure, Secondary KW - Disulfides -- chemistry KW - Guanidine -- chemistry KW - Protein Denaturation KW - Mesocricetus KW - Circular Dichroism KW - Aspartic Acid -- chemistry KW - Mutagenesis KW - Cricetinae KW - Cell-Free System KW - Prions -- genetics KW - Prions -- chemistry KW - Salts -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73140600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+role+of+helix+1+aspartates+and+salt+bridges+in+the+stability+and+conversion+of+prion+protein.&rft.au=Speare%2C+Jonathan+O%3BRush%2C+Thomas+S%3BBloom%2C+Marshall+E%3BCaughey%2C+Byron&rft.aulast=Speare&rft.aufirst=Jonathan&rft.date=2003-04-04&rft.volume=278&rft.issue=14&rft.spage=12522&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 - 2003-05-19 N1 - Date created - 2003-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ggamma subunit-selective G protein beta 5 mutant defines regulators of G protein signaling protein binding requirement for nuclear localization. AN - 73139987; 12551930 AB - The signal transducing function of Gbeta(5) in brain is unknown. When studied in vitro Gbeta(5) is the only heterotrimeric Gbeta subunit known to interact with both Ggamma subunits and regulators of G protein signaling (RGS) proteins. When tested with Ggamma, Gbeta(5) interacts with other classical components of heterotrimeric G protein signaling pathways such as Galpha and phospholipase C-beta. We recently demonstrated nuclear expression of Gbeta(5) in neurons and brain (Zhang, J. H., Barr, V. A., Mo, Y., Rojkova, A. M., Liu, S., and Simonds, W. F. (2001) J. Biol. Chem. 276, 10284-10289). To gain further insight into the mechanism of Gbeta(5) nuclear localization, we generated a Gbeta(5) mutant deficient in its ability to interact with RGS7 while retaining its ability to bind Ggamma, and we compared its properties to the wild-type Gbeta(5). In HEK-293 cells co-transfection of RGS7 but not Ggamma(2) supported expression in the nuclear fraction of transfected wild-type Gbeta(5). In contrast the Ggamma-preferring Gbeta(5) mutant was not expressed in the HEK-293 cell nuclear fraction with either co-transfectant. The Ggamma-selective Gbeta(5) mutant was also excluded from the cell nucleus of transfected PC12 cells analyzed by laser confocal microscopy. These results define a requirement for RGS protein binding for Gbeta(5) nuclear expression. JF - The Journal of biological chemistry AU - Rojkova, Alexandra M AU - Woodard, Geoffrey E AU - Huang, Tzu-Chuan AU - Combs, Christian A AU - Zhang, Jian-Hua AU - Simonds, William F AD - Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/04/04/ PY - 2003 DA - 2003 Apr 04 SP - 12507 EP - 12512 VL - 278 IS - 14 SN - 0021-9258, 0021-9258 KW - GNB5 protein, human KW - 0 KW - GTP-Binding Protein beta Subunits KW - Gnb5 protein, rat KW - Protein Sorting Signals KW - RGS Proteins KW - RGS7 protein, human KW - Rgs7 protein, mouse KW - Rgs7 protein, rat KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Heterotrimeric GTP-Binding Proteins KW - EC 3.6.5.1 KW - Index Medicus KW - Animals KW - Cytosol -- metabolism KW - Protein Sorting Signals -- genetics KW - Cell Nucleus -- metabolism KW - Humans KW - RGS Proteins -- metabolism KW - Gene Expression KW - Mutagenesis -- physiology KW - Amino Acid Sequence KW - GTP-Binding Proteins -- genetics KW - Rats KW - RGS Proteins -- genetics KW - Transfection KW - GTP-Binding Proteins -- metabolism KW - Kidney -- cytology KW - Molecular Sequence Data KW - Protein Structure, Tertiary KW - PC12 Cells KW - Active Transport, Cell Nucleus -- physiology KW - Heterotrimeric GTP-Binding Proteins -- genetics KW - Heterotrimeric GTP-Binding Proteins -- metabolism KW - Heterotrimeric GTP-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73139987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ggamma+subunit-selective+G+protein+beta+5+mutant+defines+regulators+of+G+protein+signaling+protein+binding+requirement+for+nuclear+localization.&rft.au=Rojkova%2C+Alexandra+M%3BWoodard%2C+Geoffrey+E%3BHuang%2C+Tzu-Chuan%3BCombs%2C+Christian+A%3BZhang%2C+Jian-Hua%3BSimonds%2C+William+F&rft.aulast=Rojkova&rft.aufirst=Alexandra&rft.date=2003-04-04&rft.volume=278&rft.issue=14&rft.spage=12507&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 - 2003-05-19 N1 - Date created - 2003-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a functionally important conformation-sensitive region of the secretory Na+-K+-2Cl- cotransporter (NKCC1). AN - 73132770; 12556450 AB - The secretory Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) is a member of a small gene family of electroneutral salt transporters that play essential roles in salt and water homeostasis in many mammalian tissues. We have identified a highly conserved residue (Ala-483) in the sixth membrane-spanning segment of rat NKCC1 that when mutated to cysteine renders the transporter sensitive to inhibition by the sulfhydryl reagents 2-aminoethyl methanethiosulfonate (MTSEA) and 2-(trimethylammonium)ethyl methanethiosulfonate (MTSET). The mutation of Ala-483 to cysteine (A483C) results in little or no change in the affinities of NKCC1 for substrate ions but produces a 6-fold increase in sensitivity to the inhibitor bumetanide, suggesting a specific modification of the bumetanide binding site. When residues surrounding Ala-483 were mutated to cysteine, only I484C was sensitive to inhibition by MTSEA and MTSET. Surprisingly I484C showed increased transport activity in the presence of low concentrations of mercury (1-10 microm), whereas A483C showed inhibition. The inhibition of A483C by MTSEA was unaffected by the presence or absence of sodium and potassium but required the presence of extracellular chloride. Taken together, our results indicate that Ala-483 lies at or near an important functional site of NKCC1 and that the exposure of this site to the extracellular medium is dependent on the conformation of the transporter. Specifically, our results indicate that the cysteine introduced at residue 483 is only available for interaction with MTSEA when chloride is bound to NKCC1 at the extracellular surface. JF - The Journal of biological chemistry AU - Dehaye, J P AU - Nagy, Akos AU - Premkumar, Anita AU - Turner, R James AD - Membrane Biology Section, Gene Therapy and Therapeutics Branch, NIDCR, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA. Y1 - 2003/04/04/ PY - 2003 DA - 2003 Apr 04 SP - 11811 EP - 11817 VL - 278 IS - 14 SN - 0021-9258, 0021-9258 KW - Mesylates KW - 0 KW - Rubidium Radioisotopes KW - SLC12A2 protein, human KW - Slc12a2 protein, rat KW - Sodium-Potassium-Chloride Symporters KW - Solute Carrier Family 12, Member 2 KW - Sulfhydryl Reagents KW - methanethiosulfonate ethylammonium KW - (2-(trimethylammonium)ethyl)methanethiosulfonate KW - 155450-08-1 KW - Ethyl Methanesulfonate KW - 9H154DI0UP KW - Mercury KW - FXS1BY2PGL KW - Cysteine KW - K848JZ4886 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Animals KW - Mercury -- pharmacology KW - Cysteine -- genetics KW - Humans KW - Mutagenesis -- physiology KW - Amino Acid Sequence KW - Biological Transport -- drug effects KW - Rats KW - Extracellular Space -- metabolism KW - Molecular Sequence Data KW - Kidney -- cytology KW - Sulfhydryl Reagents -- pharmacology KW - Alanine -- genetics KW - Biological Transport -- physiology KW - Cell Line KW - Protein Conformation KW - Mesylates -- pharmacology KW - Ethyl Methanesulfonate -- analogs & derivatives KW - Sodium-Potassium-Chloride Symporters -- chemistry KW - Sodium-Potassium-Chloride Symporters -- metabolism KW - Ethyl Methanesulfonate -- pharmacology KW - Sodium-Potassium-Chloride Symporters -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73132770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+a+functionally+important+conformation-sensitive+region+of+the+secretory+Na%2B-K%2B-2Cl-+cotransporter+%28NKCC1%29.&rft.au=Dehaye%2C+J+P%3BNagy%2C+Akos%3BPremkumar%2C+Anita%3BTurner%2C+R+James&rft.aulast=Dehaye&rft.aufirst=J&rft.date=2003-04-04&rft.volume=278&rft.issue=14&rft.spage=11811&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 - 2003-05-19 N1 - Date created - 2003-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro and in vivo studies of MutS, MutL and MutH mutants: correlation of mismatch repair and DNA recombination AN - 18732459; 5613501 AB - We have used the recently determined crystal structures of Escherichia coli (E. coli) MutS, MutL and MutH to guide construction of 47 amino-acid substitutions in these proteins and analyzed their behavior in mismatch repair and recombination in vitro and in vivo. We find that the active site of the MutH endonuclease is composed of regions from two separate structural domains and that the C-terminal 5 residues of MutH influence both DNA binding and cleavage. We also find that the non-specific DNA-binding activity of MutL is required for mismatch repair and probably functions after strand cleavage by MutH. Alteration of residues in either the mismatch recognition domain, the ATPase active site, or the domain interfaces linking the two activities can diminish the differential binding of MutS to homoduplex versus heteroduplex and results in the loss of mismatch-specific MutH activation. Finally, every mutation that abolishes mismatch repair is deficient in blocking homeologous recombination, suggesting that mismatch repair and prevention of homeologous recombination use the same MutS-MutL complexes for signaling in E. coli. JF - DNA Repair AU - Junop AU - Yang, W AU - Funchain, P AU - Clendenin, W AU - Miller, J H AD - Laboratory of Molecular Biology, NIDDK, National Institutes of Health, 9000 Rockville Pike, Bldg 5, Room B1-03, Bethesda, MD 20892, USA, wei.yang@nih.gov Y1 - 2003/04/02/ PY - 2003 DA - 2003 Apr 02 SP - 387 EP - 405 PB - Elsevier Science VL - 2 IS - 4 SN - 1568-7864, 1568-7864 KW - MutH protein KW - MutL protein KW - MutS protein KW - mismatch repair KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - J 02725:DNA KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18732459?accountid=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=DNA+Repair&rft.atitle=In+vitro+and+in+vivo+studies+of+MutS%2C+MutL+and+MutH+mutants%3A+correlation+of+mismatch+repair+and+DNA+recombination&rft.au=Junop%3BYang%2C+W%3BFunchain%2C+P%3BClendenin%2C+W%3BMiller%2C+J+H&rft.aulast=Junop&rft.aufirst=&rft.date=2003-04-02&rft.volume=2&rft.issue=4&rft.spage=387&rft.isbn=&rft.btitle=&rft.title=DNA+Repair&rft.issn=15687864&rft_id=info:doi/10.1016%2FS1568-7864%2802%2900245-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S1568-7864(02)00245-8 ER - TY - JOUR T1 - Treatment of unresectable hepatocellular carcinoma less than 2 centimeters by transcatheter arterial chemoembolization with autologous blood clot. AN - 85366633; pmid-12642743 AB - To assess the efficacy of transcatheter arterial chemoembolization using autologous blood clot as an embolizing agent (short-TAE [S-TAE]) for the treatment of unresectable hepatocellular carcinoma less than 2 cm.Twenty-eight consecutive patients with unresectable hepatocellular carcinoma less than 2 cm in diameter were treated by S-TAE alone. All patients had documented cirrhosis (Child class B:C = 20:8). S-TAE was performed by injecting a mixture of iodized oil and anticancer drugs followed by embolization of hepatic arteries with autologous blood clot.A total of 147 sessions of embolization with clots were performed. S-TAE maintained patency of hepatic arteries. The overall survival rates at 1, 3, 5, and 8 years were estimated to be 89%, 52%, 34%, and 17%, respectively, which were better compared with prior records for the gelfoam method. The survival rates for Child class B patients were significantly better than that for Child class C patients (P < 0.05). The Cox proportional hazard model also demonstrated that Child staging of cirrhosis was the sole factor significantly predicting the survival (P < 0.05).The long-term outcomes of S-TAE for unresectable hepatocellular carcinoma less than 2 cm are satisfactory. Prognosis of these patients was significantly dependent on clinical stages of coexisting liver cirrhosis. JF - Journal of clinical gastroenterology AU - Gunji, Toshiaki AU - Kawauchi, Nobuo AU - Akahane, Masao AU - Watanabe, Kiyotaka AU - Kanamori, Hiroshi AU - Ohnishi, Shin AD - Third Department of Internal Medicine, University of Tokyo, Japan. ToshiakiG@intra.niddk.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 347 EP - 351 VL - 36 IS - 4 SN - 0192-0790, 0192-0790 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Carcinoma, Hepatocellular: mortality KW - *Carcinoma, Hepatocellular: pathology KW - *Carcinoma, Hepatocellular: therapy KW - Catheterization KW - *Chemoembolization, Therapeutic: methods KW - Female KW - Gelatin Sponge, Absorbable KW - Humans KW - Liver Neoplasms: mortality KW - *Liver Neoplasms: pathology KW - *Liver Neoplasms: therapy KW - Male KW - Middle Aged KW - Neoplasm Staging KW - *Palliative Care: methods KW - Probability KW - Prognosis KW - Proportional Hazards Models KW - Prospective Studies KW - Risk Assessment KW - Sampling Studies KW - Statistics, Nonparametric KW - Survival Analysis KW - Terminally Ill KW - Treatment Outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85366633?accountid=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=Treatment+of+unresectable+hepatocellular+carcinoma+less+than+2+centimeters+by+transcatheter+arterial+chemoembolization+with+autologous+blood+clot.&rft.au=Gunji%2C+Toshiaki%3BKawauchi%2C+Nobuo%3BAkahane%2C+Masao%3BWatanabe%2C+Kiyotaka%3BKanamori%2C+Hiroshi%3BOhnishi%2C+Shin&rft.aulast=Gunji&rft.aufirst=Toshiaki&rft.date=2003-04-01&rft.volume=36&rft.issue=4&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+gastroenterology&rft.issn=01920790&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Words in melody: an H215O PET study of brain activation during singing and speaking. AN - 85279998; pmid-12692476 AB - We used H(2)15O PET to characterize the interaction of words and melody by comparing brain activity measured while subjects spoke or sang the words to a familiar song. Relative increases in activity during speaking vs singing were observed in the left hemisphere, in classical perisylvian language areas including the posterior superior temporal gyrus, supramarginal gyrus, and frontal operculum, as well as in Rolandic cortices and putamen. Relative increases in activity during singing were observed in the right hemisphere: these were maximal in the right anterior superior temporal gyrus and contiguous portions of the insula; relative increases associated with singing were also detected in the right anterior middle temporal gyrus and superior temporal sulcus, medial and dorsolateral prefrontal cortices, mesial temporal cortices and cerebellum, as well as in Rolandic cortices and nucleus accumbens. These results indicate that the production of words in song is associated with activation of regions within right hemisphere areas that are not mirror-image homologues of left hemisphere perisylvian language areas, and suggest that multiple neural networks may be involved in different aspects of singing. Right hemisphere mechanisms may support the fluency-evoking effects of singing in neurological disorders such as stuttering or aphasia. JF - Neuroreport AU - Jeffries, K J AU - Fritz, J B AU - Braun, Allen R AD - National Institute on Deafness and Other Communication Disorders PY - 2003 SP - 749 EP - 754 VL - 14 IS - 5 SN - 0959-4965, 0959-4965 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85279998?accountid=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=Neuroreport&rft.atitle=Words+in+melody%3A+an+H215O+PET+study+of+brain+activation+during+singing+and+speaking.&rft.au=Jeffries%2C+K+J%3BFritz%2C+J+B%3BBraun%2C+Allen+R&rft.aulast=Jeffries&rft.aufirst=K&rft.date=2003-04-01&rft.volume=14&rft.issue=5&rft.spage=749&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Intravenous nicotine reduces cerebral glucose metabolism: a preliminary study. AN - 85270889; pmid-12655323 AB - Nicotine is self-administered by smoking tobacco products, and enhances positive mood (at least in smokers). Since most drugs of abuse decrease regional cerebral metabolic rate(s) for glucose (rCMRglc) in human subjects, we posited that administration of nicotine would similarly reduce rCMRglc. Positron emission tomography (PET) with [F-18]fluorodeoxyglucose was used to assess the effects of intravenous nicotine (1.5 mg) on cerebral glucose metabolism in six healthy male volunteers (21-38 years of age). Two PET assays (placebo and nicotine) were performed, and subjective self-reports of mood and feeling state were collected. Data were analyzed using analysis of variance. Nicotine reduced global glucose metabolism (by 9.51% of placebo control), with reductions in most of the 30 individual regions tested. Nine regions had bilateral effects that reached statistical significance (p&<0.05, uncorrected for the number of regions tested), although the statistical model used did not separate these effects from a global effect. The subjects reported both positive and negative effects of nicotine on mood/feeling state. The widespread decreases in cerebral metabolism are consistent with the many effects of nicotine on cognition and mood. The findings indicate that nicotine resembles other drugs of abuse in reducing brain metabolism, perhaps by a common mechanism. JF - Neuropsychopharmacology AU - Stapleton, June M AU - Gilson, Stephen F AU - Wong, Dean F AU - Villemagne, Victor L AU - Dannals, Robert F AU - Grayson, Roger F AU - Henningfield Jack E AU - London, Edythe D AD - Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA. PY - 2003 SP - 765 EP - 772 VL - 28 IS - 4 SN - 0893-133X, 0893-133X KW - Analysis of Variance KW - Comparative Study KW - Infusions, Intravenous KW - Nicotine KW - Human KW - Adult KW - Brain KW - Glucose KW - Affect KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85270889?accountid=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=Neuropsychopharmacology&rft.atitle=Intravenous+nicotine+reduces+cerebral+glucose+metabolism%3A+a+preliminary+study.&rft.au=Stapleton%2C+June+M%3BGilson%2C+Stephen+F%3BWong%2C+Dean+F%3BVillemagne%2C+Victor+L%3BDannals%2C+Robert+F%3BGrayson%2C+Roger+F%3BHenningfield+Jack+E%3BLondon%2C+Edythe+D&rft.aulast=Stapleton&rft.aufirst=June&rft.date=2003-04-01&rft.volume=28&rft.issue=4&rft.spage=765&rft.isbn=&rft.btitle=&rft.title=Neuropsychopharmacology&rft.issn=0893133X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Dissociating the roles of the rostral anterior cingulate and the lateral prefrontal cortices in performing two tasks simultaneously or successively. AN - 85269925; pmid-12631562 AB - A fundamental question about the nature of cognitive control is whether performing two tasks successively or simultaneously activates distinct brain regions. To investigate this question, we designed a functional magnetic resonance imaging (fMRI) study that compared task-switching and dual-task performance. The results showed that performing two tasks successively or simultaneously activated a common prefronto-parietal neural network relative to performing each task separately. More importantly, we found that the anterior cingulate and the lateral prefrontal cortices were differently activated in dual-task and task-switching situations. When performing two tasks simultaneously, as compared to performing them in succession, activation was found in the rostral anterior cingulate cortex. In contrast, switching between two tasks, relative to performing them simultaneously, activated the left lateral prefrontal cortex and the bilateral intra-parietal sulcus region. We interpret these results as indicating that the rostral anterior cingulate cortex serves to resolve conflicts between stimulus-response associations when performing two tasks simultaneously, while the lateral prefrontal cortex dynamically selects the neural pathways needed to perform a given task during task switching. JF - Cerebral Cortex AU - Dreher Jean-Claude AU - Grafman Jordan AD - Cognitive Neuroscience Section, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, MD 20892-1440, USA. PY - 2003 SP - 329 EP - 339 VL - 13 IS - 4 SN - 1047-3211, 1047-3211 KW - Magnetic Resonance Imaging KW - Brain Mapping KW - Photic Stimulation KW - Comparative Study KW - Gyrus Cinguli KW - Human KW - Adult KW - Neural Pathways KW - Psychomotor Performance KW - Prefrontal Cortex UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85269925?accountid=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=Cerebral+Cortex&rft.atitle=Dissociating+the+roles+of+the+rostral+anterior+cingulate+and+the+lateral+prefrontal+cortices+in+performing+two+tasks+simultaneously+or+successively.&rft.au=Dreher+Jean-Claude%3BGrafman+Jordan&rft.aulast=Dreher+Jean-Claude&rft.aufirst=&rft.date=2003-04-01&rft.volume=13&rft.issue=4&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Cerebral+Cortex&rft.issn=10473211&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Modulation of neural activity during object naming: effects of time and practice. AN - 85267302; pmid-12631567 AB - Repeated exposure to objects improves our ability to identify and name them, even after a long delay. Previous brain imaging studies have demonstrated that this experience-related facilitation of object naming is associated with neural changes in distinct brain regions. We used event-related functional magnetic resonance imaging (fMRI) to examine the modulation of neural activity in the object naming system as a function of experience and time. Pictures of common objects were presented repeatedly for naming at different time intervals (1 h, 6 h and 3 days) before scanning, or at 30 s intervals during scanning. The results revealed that as objects became more familiar with experience, activity in occipitotemporal and left inferior frontal regions decreased while activity in the left insula and basal ganglia increased. In posterior regions, reductions in activity as a result of multiple repetitions did not interact with time, whereas in left inferior frontal cortex larger decreases were observed when repetitions were spaced out over time. This differential modulation of activity in distinct brain regions provides support for the idea that long-lasting object priming is mediated by two neural mechanisms. The first mechanism may involve changes in object-specific representations in occipitotemporal cortices, the second may be a form of procedural learning involving a reorganization in brain circuitry that leads to more efficient name retrieval. JF - Cerebral Cortex AU - van Turennout Miranda AU - Bielamowicz, Lisa AU - Martin, Alex AD - Laboratory of Brain and Cognition, National Institute of Mental Health, Bethesda, MD, USA. PY - 2003 SP - 381 EP - 391 VL - 13 IS - 4 SN - 1047-3211, 1047-3211 KW - Magnetic Resonance Imaging KW - Analysis of Variance KW - Recognition (Psychology) KW - Human KW - Adult KW - Brain KW - Time Factors KW - Female KW - Male KW - Synaptic Transmission KW - Reaction Time KW - Practice (Psychology) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85267302?accountid=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=Cerebral+Cortex&rft.atitle=Modulation+of+neural+activity+during+object+naming%3A+effects+of+time+and+practice.&rft.au=van+Turennout+Miranda%3BBielamowicz%2C+Lisa%3BMartin%2C+Alex&rft.aulast=van+Turennout+Miranda&rft.aufirst=&rft.date=2003-04-01&rft.volume=13&rft.issue=4&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=Cerebral+Cortex&rft.issn=10473211&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Tapping the power of small institutions. AN - 85265467; pmid-12686973 JF - Nature AU - Keusch, Gerald T AU - Medlin, Carol A AD - Fogarty International Center, National Institutes of Health, Bethesda Maryland 20892, USA. PY - 2003 SP - 561 EP - 562 VL - 422 IS - 6932 SN - 0028-0836, 0028-0836 KW - World Health Organization KW - Politics KW - Developing Countries KW - Public Health KW - Biomedical Research KW - Internationality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85265467?accountid=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=Nature&rft.atitle=Tapping+the+power+of+small+institutions.&rft.au=Keusch%2C+Gerald+T%3BMedlin%2C+Carol+A&rft.aulast=Keusch&rft.aufirst=Gerald&rft.date=2003-04-01&rft.volume=422&rft.issue=6932&rft.spage=561&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Defining the conductance of the closed state in a voltage-gated K+ channel. AN - 85244789; pmid-12691664 AB - The opening and closing of the ion conduction pathway in ion channels underlies the generation and propagation of electrical signals in biological systems. Although electrophysiological approaches to measuring the flow of ions in the open state have contributed profoundly to our understanding of ion permeation and gating, it remains unclear how much the ion-throughput rate decreases upon closure of the ion conduction pore. To address this fundamental question, we expressed the Shaker Kv channel at high levels and then measured macroscopic K+ currents at negative membrane voltages and counted the number of channels by quantifying the translocation of gating charge. Our results show that the conductance of the closed state is between 0 and 0.16 fS, or at least 100,000 times lower than for the open state of the channel, indicating that the flow of ions is very tightly regulated in this class of K+ channels. JF - Neuron AU - Soler-Llavina, Gilberto J AU - Holmgren, Miguel AU - Swartz, Kenton J AD - Molecular Physiology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 2003 SP - 61 EP - 67 VL - 38 IS - 1 SN - 0896-6273, 0896-6273 KW - Animals KW - Ion Channel Gating KW - Xenopus laevis KW - Patch-Clamp Techniques KW - Electric Conductivity KW - Membrane Potentials KW - Oocytes KW - Potassium KW - Protein Structure, Tertiary KW - Drosophila KW - Potassium Channels KW - Protein Structure, Quaternary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85244789?accountid=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=Neuron&rft.atitle=Defining+the+conductance+of+the+closed+state+in+a+voltage-gated+K%2B+channel.&rft.au=Soler-Llavina%2C+Gilberto+J%3BHolmgren%2C+Miguel%3BSwartz%2C+Kenton+J&rft.aulast=Soler-Llavina&rft.aufirst=Gilberto&rft.date=2003-04-01&rft.volume=38&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Rewarding injections of the cholinergic agonist carbachol into the ventral tegmental area induce locomotion and c-Fos expression in the retrosplenial area and supramammillary nucleus. AN - 85237413; pmid-12676367 AB - Previously we found that intra-ventral tegmental injections of the cholinergic agonist carbachol induce reward; such injections induce conditioned place preference and rats learn quickly to self-administer carbachol directly into the ventral tegmental area (VTA). To determine what brain regions are activated by such rewarding injections we studied the expression of the transcription factor c-Fos in local and distant brain regions following ventral tegmental injections of carbachol in rats. We also measured locomotion induced by such injections. Carbachol injections into the VTA induced vigorous locomotion while carbachol injections into the regions 1 mm dorsal or 1 mm lateral to the VTA induced delayed attenuated locomotion. Ventral tegmental injections of carbachol induced c-Fos expression throughout the brain. Significant correlations between locomotion c-Fos positive nuclei were found in the retrosplenial area the posterior hypothalamus including the supramammillary nucleus. These results suggest that the retrosplenial area supramammillary nucleus may be parts of the circuitry for the reward triggered by ventral tegmental cholinergic stimulation. JF - Brain Research AU - Ikemoto Satoshi AU - Witkin, Brian M AU - Morales Marisela AD - Behavioral Neuroscience Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, 21224, Baltimore, MD, USA PY - 2003 SP - 78 EP - 87 VL - 969 IS - 1-2 SN - 0006-8993, 0006-8993 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85237413?accountid=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+Research&rft.atitle=Rewarding+injections+of+the+cholinergic+agonist+carbachol+into+the+ventral+tegmental+area+induce+locomotion+and+c-Fos+expression+in+the+retrosplenial+area+and+supramammillary+nucleus.&rft.au=Ikemoto+Satoshi%3BWitkin%2C+Brian+M%3BMorales+Marisela&rft.aulast=Ikemoto+Satoshi&rft.aufirst=&rft.date=2003-04-01&rft.volume=969&rft.issue=1-2&rft.spage=78&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Novel Technique for Cardiac Electromechanical Mapping with Magnetic Resonance Imaging Tagging and an Epicardial Electrode Sock AN - 831176453; 13866586 AB - Near-simultaneous measurements of electrical and mechanical activation over the entire ventricular surface are now possible using magnetic resonance imaging tagging and a multielectrode epicardial sock. This new electromechanical mapping technique is demonstrated in the ventricularly paced canine heart. A 128-electrode epicardial sock and pacing electrodes were placed on the hearts of four anesthetized dogs. In the magnetic resonance scanner, tagged cine images (8-15 ms/frame) and sock electrode recordings (1000 Hz) were acquired under right-ventricular pacing and temporally referenced to the pacing stimulus. Electrical recordings were obtained during intermittent breaks in image acquisition, so that both data sets represented the same physiologic state. Since the electrodes were not visible in the images, electrode recordings and cine images were spatially registered with Gd-DTPA markers attached to the sock. Circumferential strain was calculated at locations corresponding to electrodes. For each electrode location, electrical and mechanical activation times were calculated and relationships between the two activation patterns were demonstrated. This method holds promise for improving understanding of the relationships between the patterns of electrical activation and contraction in the heart. [copy 2003 Biomedical Engineering Society. PAC2003: 8761Pk, 8719Rr, 8719Hh JF - Annals of Biomedical Engineering AU - Faris, Owen P AU - Evans, Frank J AU - Ennis, Daniel B AU - Helm, Patrick A AU - Taylor, Joni L AU - Chesnick, AScott AU - Guttman, Michael A AU - Ozturk, Cengizhan AU - McVeigh, Elliot R AD - Laboratory of Cardiac Energetics, National Institutes of Health, NHLBI, 10 Center Drive, Room B1D416, Bethesda, MD Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 430 EP - 440 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 31 IS - 4 SN - 0090-6964, 0090-6964 KW - Biotechnology and Bioengineering Abstracts KW - Heart KW - Data processing KW - Electrodes KW - Magnetic resonance imaging KW - N.M.R. KW - Mapping KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/831176453?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+Biomedical+Engineering&rft.atitle=Novel+Technique+for+Cardiac+Electromechanical+Mapping+with+Magnetic+Resonance+Imaging+Tagging+and+an+Epicardial+Electrode+Sock&rft.au=Faris%2C+Owen+P%3BEvans%2C+Frank+J%3BEnnis%2C+Daniel+B%3BHelm%2C+Patrick+A%3BTaylor%2C+Joni+L%3BChesnick%2C+AScott%3BGuttman%2C+Michael+A%3BOzturk%2C+Cengizhan%3BMcVeigh%2C+Elliot+R&rft.aulast=Faris&rft.aufirst=Owen&rft.date=2003-04-01&rft.volume=31&rft.issue=4&rft.spage=430&rft.isbn=&rft.btitle=&rft.title=Annals+of+Biomedical+Engineering&rft.issn=00906964&rft_id=info:doi/10.1114%2F1.1560618 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2015-03-19 N1 - SubjectsTermNotLitGenreText - Heart; Data processing; Magnetic resonance imaging; Electrodes; N.M.R.; Mapping DO - http://dx.doi.org/10.1114/1.1560618 ER - TY - JOUR T1 - A Computational Model of Direct Interstitial Infusion of Macromolecules into the Spinal Cord AN - 831166891; 13866588 AB - Convection-enhanced interstitial infusion can deliver macromolecular drugs to large tissue volumes of the central nervous system. To characterize infusion into the spinal cord, an image-based three-dimensional finite element model of the rat spinal cord was developed. The model incorporated convection and diffusion through white and gray matter, including anisotropic transport due to alignment of white matter tracts. Spatial and temporal distribution of the marker substance albumin within the interstitial space was determined. Consistent with previous experiments, predicted distribution was highly anisotropic. Infusing into the dorsal column, albumin was primarily confined to white matter with limited penetration into adjacent gray matter. Distribution was determined primarily by the ratio of fiber-parallel to fiber-perpendicular hydraulic conductivity tensor components (k sub(wm-z)/k sub(wm-x)), the ratio of transverse white and gray matter hydraulic conductivity (k sub(wm-x)/k sub(gm)), and tissue porosity. Fits to previous experimental measures of axial and transverse spread, distribution volume, and protein recovery yielded an optimum k sub(wm-z)/k sub(wm-x) of approximately 20 at 0.1 kl/min. k sub(wm-x)/k sub(gm) of 100 was sufficient to match experimental transverse distribution data. Best fits to data at 0.1 kl/min were achieved by porosities characteristic of moderate edema (e.g., 0.26). Distribution also varied with catheter placement with more medial placement resulting in greater distribution volumes. [copy 2003 Biomedical Engineering Society. PAC2003: 8719La, 8715Vv, 8710+e JF - Annals of Biomedical Engineering AU - Sarntinoranont, Malisa AU - Banerjee, Rupak K AU - Lonser, Russell R AU - Morrison, Paul F AD - Division of Bioengineering and Physical Science ORS, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 448 EP - 461 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 31 IS - 4 SN - 0090-6964, 0090-6964 KW - CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - Convection KW - Central nervous system KW - Hydraulics KW - Macromolecules KW - Data processing KW - Anisotropy KW - Mathematical models KW - Spinal cord KW - Porosity KW - Animal models KW - Substantia alba KW - Edema KW - Dorsal columns KW - Albumin KW - Catheters KW - Diffusion KW - Drugs KW - Substantia grisea KW - N3 11002:Computational & theoretical neuroscience KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/831166891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+Biomedical+Engineering&rft.atitle=A+Computational+Model+of+Direct+Interstitial+Infusion+of+Macromolecules+into+the+Spinal+Cord&rft.au=Sarntinoranont%2C+Malisa%3BBanerjee%2C+Rupak+K%3BLonser%2C+Russell+R%3BMorrison%2C+Paul+F&rft.aulast=Sarntinoranont&rft.aufirst=Malisa&rft.date=2003-04-01&rft.volume=31&rft.issue=4&rft.spage=448&rft.isbn=&rft.btitle=&rft.title=Annals+of+Biomedical+Engineering&rft.issn=00906964&rft_id=info:doi/10.1114%2F1.1558032 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2015-03-19 N1 - SubjectsTermNotLitGenreText - Convection; Hydraulics; Central nervous system; Macromolecules; Mathematical models; Anisotropy; Data processing; Spinal cord; Porosity; Animal models; Edema; Substantia alba; Dorsal columns; Albumin; Catheters; Diffusion; Drugs; Substantia grisea DO - http://dx.doi.org/10.1114/1.1558032 ER - TY - JOUR T1 - Absence of carcinogenic activity in Fischer rats and B6C3F1 mice following 103-week inhalation exposures to toluene. AN - 73442984; 12848242 AB - Toluene, methylbenzene, is used to back-blend gasoline, as a chemical intermediate, and as a solvent; more than 7 million tonnes are produced each year in the United States. Following 14-15-week toxicity studies to estimate appropriate exposure concentrations for the carcinogenesis bioassays, toxicology and carcinogenesis studies of toluene (>99% pure) were conducted by whole-body inhalation exposures of F344/N rats and B6C3F1 mice of each sex for 15 months or two years. Toluene levels were 0 (chamber controls), 600, and 1,200 ppm for rats and 0, 120, 600, and 1200 ppm for mice. Exposures were 6.5 hr/day 5 days/wk. Genetic toxicology studies using Salmonella typhimurium, mouse L5178Y lymphoma cells, and Chinese hamster ovary cells were negative. No chemically related neoplasm was found in male rats, and one nasal, two kidney, and two forestomach neoplasms observed in female rats were considered not to be associated with the toluene exposure. For mice, no biologically important increase was observed for any nonneoplastic or neoplastic lesion. Studies by others had reported carcinogenicity of toluene, especially for total malignant tumors. JF - International journal of occupational and environmental health AU - Huff, James AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. huff1@niehs.nih.gov PY - 2003 SP - 138 EP - 146 VL - 9 IS - 2 SN - 1077-3525, 1077-3525 KW - Carcinogens KW - 0 KW - Solvents KW - Toluene KW - 3FPU23BG52 KW - Index Medicus KW - Animals KW - Nasal Mucosa -- pathology KW - Body Weights and Measures KW - Respiratory Mucosa -- drug effects KW - Biological Assay KW - Mice KW - Nasal Mucosa -- drug effects KW - Respiratory Mucosa -- pathology KW - Neoplasms, Unknown Primary -- chemically induced KW - Rats KW - Rats, Inbred F344 KW - Toxicity Tests, Chronic KW - Carcinogenicity Tests KW - Administration, Inhalation KW - Salmonella typhimurium -- genetics KW - Female KW - Male KW - Kidney Diseases -- chemically induced KW - Models, Animal KW - Solvents -- toxicity KW - Toluene -- administration & dosage KW - Neoplasms, Experimental -- chemically induced KW - Solvents -- administration & dosage KW - Carcinogens -- toxicity KW - Toluene -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73442984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+occupational+and+environmental+health&rft.atitle=Absence+of+carcinogenic+activity+in+Fischer+rats+and+B6C3F1+mice+following+103-week+inhalation+exposures+to+toluene.&rft.au=Huff%2C+James&rft.aulast=Huff&rft.aufirst=James&rft.date=2003-04-01&rft.volume=9&rft.issue=2&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=International+journal+of+occupational+and+environmental+health&rft.issn=10773525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-16 N1 - Date created - 2003-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupation and larynx and hypopharynx cancer: a job-exposure matrix approach in an international case-control study in France, Italy, Spain and Switzerland. AN - 73393148; 12814200 AB - To investigate the effect of exposure to occupational agents on the risk of hypopharyngeal/laryngeal cancer. Case-control study conducted during 1979-1982 in six centres in South Europe. An occupational history and information on exposure to non-occupational factors were collected for 1010 male cases of hypopharyngeal/ laryngeal cancer as well as for 2176 population controls. The exposure to 10 occupational agents was assessed through a job-exposure matrix. As occupational histories had been collected since 1945 major analyses were restricted to subjects aged less than 55 years (315 cases and 819 controls). Significant elevated risks adjusted for non-occupational variables (smoking, alcohol consumption and diet) and other occupational exposures were consistently found for organic solvents (odds ratio (OR) for ever-exposure: 1.7, 95% confidence interval: 1.1-2.5) and asbestos (OR: 1.6, 1.0-2.5). A significant positive trend for both probability of exposure and duration was found for exposure to solvents. A positive association between exposure to formaldehyde and laryngeal cancer was also suggested. No association was found for exposure to arsenic and compounds, chromium and compounds, and polycyclic aromatic hydrocarbons. Analyses restricted to subjects aged 55 or more did not show elevated risks, with the exception of wood dust (OR: 1.8, 1.3-2.7). In our study occupational exposure to solvents was associated with an increased risk of hypopharyngeal/laryngeal cancer. Results also provide additional evidence of an excess of risk for exposure to asbestos. JF - Cancer causes & control : CCC AU - Berrino, Franco AU - Richiardi, Lorenzo AU - Boffetta, Paolo AU - Estève, Jacques AU - Belletti, Isabella AU - Raymond, Luc AU - Troschel, Loredana AU - Pisani, Paola AU - Zubiri, Lourdes AU - Ascunce, Nieves AU - Gubéran, Etienne AU - Tuyns, Albert AU - Terracini, Benedetto AU - Merletti, Franco AU - Milan JEM Working Group AD - Epidemiology Unit, National Cancer Institute, Milan, Italy. ; Milan JEM Working Group Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 213 EP - 223 VL - 14 IS - 3 SN - 0957-5243, 0957-5243 KW - Solvents KW - 0 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Odds Ratio KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Europe -- epidemiology KW - Male KW - Female KW - Occupational Exposure KW - Hypopharyngeal Neoplasms -- etiology KW - Hypopharyngeal Neoplasms -- epidemiology KW - Solvents -- adverse effects KW - Laryngeal Neoplasms -- epidemiology KW - Asbestos -- adverse effects KW - Occupations KW - Laryngeal Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73393148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Occupation+and+larynx+and+hypopharynx+cancer%3A+a+job-exposure+matrix+approach+in+an+international+case-control+study+in+France%2C+Italy%2C+Spain+and+Switzerland.&rft.au=Berrino%2C+Franco%3BRichiardi%2C+Lorenzo%3BBoffetta%2C+Paolo%3BEst%C3%A8ve%2C+Jacques%3BBelletti%2C+Isabella%3BRaymond%2C+Luc%3BTroschel%2C+Loredana%3BPisani%2C+Paola%3BZubiri%2C+Lourdes%3BAscunce%2C+Nieves%3BGub%C3%A9ran%2C+Etienne%3BTuyns%2C+Albert%3BTerracini%2C+Benedetto%3BMerletti%2C+Franco%3BMilan+JEM+Working+Group&rft.aulast=Berrino&rft.aufirst=Franco&rft.date=2003-04-01&rft.volume=14&rft.issue=3&rft.spage=213&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 - 2003-09-16 N1 - Date created - 2003-06-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Cancer Causes Control. 2004 May;15(4):429-30; author reply 431 [15248306] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Infertility drugs and the risk of breast cancer: findings from the National Institute of Child Health and Human Development Women's Contraceptive and Reproductive Experiences Study. AN - 73289227; 12749419 AB - To determine the association between infertility drug use and invasive breast cancer in a population-based case-control study. Multicenter case-control study. Women aged 35 to 64 years in metropolitan Atlanta, Detroit, Los Angeles, Philadelphia, and Seattle. The 4,575 case patients had histologically confirmed primary invasive breast cancer. The 4,682 control subjects were women without breast cancer identified in the same geographic locations using randomized-digit dialing. A standardized questionnaire focusing on reproductive health and family history as well as use of oral contraceptives and other hormones and infertility drugs was administered to all subjects. Data on the type of breast cancer were also obtained. Odds ratios examining the association between use of various infertility drugs and invasive breast cancer. Overall, a history of infertility drug use was not associated with the risk of developing breast cancer. Compared with women who never used any fertility medication, however, women using human menopausal gonadotropin (hMG) for > or = 6 months or for at least six cycles had a relative risk of breast cancer ranging between 2.7 to 3.8. Long-term use of certain infertility drugs could adversely affect risk of breast cancer. Additional confirmatory studies are needed. JF - Fertility and sterility AU - Burkman, Ronald T AU - Tang, Mei-Tzu C AU - Malone, Kathleen E AU - Marchbanks, Polly A AU - McDonald, Jill A AU - Folger, Suzanne G AU - Norman, Sandra A AU - Strom, Brian L AU - Bernstein, Leslie AU - Ursin, Giske AU - Weiss, Linda K AU - Daling, Janet R AU - Simon, Michael S AU - Spirtas, Robert AD - National Cancer Institute Surveillance, Epidemiology, and End Results Registry, Department of Obstetrics and Gynecology, Henry Ford Health System, Detroit, Michigan, USA. rtb@bhs.org Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 844 EP - 851 VL - 79 IS - 4 SN - 0015-0282, 0015-0282 KW - Fertility Agents, Female KW - 0 KW - Menotropins KW - 61489-71-2 KW - Index Medicus KW - Odds Ratio KW - Logistic Models KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Interviews as Topic KW - Middle Aged KW - Menotropins -- adverse effects KW - Female KW - Breast Neoplasms -- chemically induced KW - Fertility Agents, Female -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73289227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Fertility+and+sterility&rft.atitle=Infertility+drugs+and+the+risk+of+breast+cancer%3A+findings+from+the+National+Institute+of+Child+Health+and+Human+Development+Women%27s+Contraceptive+and+Reproductive+Experiences+Study.&rft.au=Burkman%2C+Ronald+T%3BTang%2C+Mei-Tzu+C%3BMalone%2C+Kathleen+E%3BMarchbanks%2C+Polly+A%3BMcDonald%2C+Jill+A%3BFolger%2C+Suzanne+G%3BNorman%2C+Sandra+A%3BStrom%2C+Brian+L%3BBernstein%2C+Leslie%3BUrsin%2C+Giske%3BWeiss%2C+Linda+K%3BDaling%2C+Janet+R%3BSimon%2C+Michael+S%3BSpirtas%2C+Robert&rft.aulast=Burkman&rft.aufirst=Ronald&rft.date=2003-04-01&rft.volume=79&rft.issue=4&rft.spage=844&rft.isbn=&rft.btitle=&rft.title=Fertility+and+sterility&rft.issn=00150282&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-05 N1 - Date created - 2003-05-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Fertil Steril. 2003 Apr;79(4):852-4; discussion 855 [12749420] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A factor analysis of the Fagerström Test for Nicotine Dependence (FTND). AN - 73279542; 12745499 AB - Psychometric study of the Fagerström Test for Nicotine Dependence (FTND) provides insight into its structure and the dimensions of nicotine addiction it assesses. We evaluated the factor structure of the FTND in 541 research volunteers, most with histories of polysubstance use. Tetrachoric and phi correlation techniques were utilized and promax- and varimax-rotated solutions are reported. Two factors were found. Factor 1 was defined by questions regarding time to first cigarette in after waking, which cigarette is most preferred, and prominence of morning smoking. Factor 2 was defined by questions regarding difficulty refraining from smoking, amount smoked, and smoking while ill. The question "How soon on waking do you smoke your first cigarette?" loaded substantially on both Factor 2 and Factor 1. Repeating the analyses after stratification by gender did not change the results. The factor structure from our sample population was similar to results reported by previous studies with different types of populations. We propose that Factor 1 assesses the degree of urgency to restore nicotine levels to a given threshold after nighttime abstinence, whereas Factor 2 reflects the persistence with which nicotine levels are maintained at about that threshold during waking hours. Thus, the FTND may assess distinguishable self-reportable pharmacological dimensions of nicotine addiction. These two dimensions may provide indirect assessment of a smoker's daily nicotine intake. Testing this hypothesis requires correlation of biomarkers and responses to specific items of the FTND. JF - Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco AU - Radzius, Aleksandras AU - Gallo, Joseph J AU - Epstein, David H AU - Gorelick, David A AU - Cadet, Jean Lud AU - Uhl, George E AU - Moolchan, Eric T AD - Intramural Research Program, National Institute on Drug Abuse National Institutes of Health Baltimore MD 21224, USA. aradzius@intra.nida.nih.gov Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 255 EP - 240 VL - 5 IS - 2 SN - 1462-2203, 1462-2203 KW - Index Medicus KW - Severity of Illness Index KW - Factor Analysis, Statistical KW - Reproducibility of Results KW - Humans KW - Adult KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Adolescent KW - Psychometrics KW - Male KW - Female KW - Tobacco Use Disorder -- epidemiology KW - Surveys and Questionnaires KW - Tobacco Use Disorder -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73279542?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.atitle=A+factor+analysis+of+the+Fagerstr%C3%B6m+Test+for+Nicotine+Dependence+%28FTND%29.&rft.au=Radzius%2C+Aleksandras%3BGallo%2C+Joseph+J%3BEpstein%2C+David+H%3BGorelick%2C+David+A%3BCadet%2C+Jean+Lud%3BUhl%2C+George+E%3BMoolchan%2C+Eric+T&rft.aulast=Radzius&rft.aufirst=Aleksandras&rft.date=2003-04-01&rft.volume=5&rft.issue=2&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=Nicotine+%26+tobacco+research+%3A+official+journal+of+the+Society+for+Research+on+Nicotine+and+Tobacco&rft.issn=14622203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-29 N1 - Date created - 2003-05-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nicotine Tob Res. 2003 Apr;5(2):141-4 [12745484] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A proportionate cancer morbidity ratio study of workers exposed to chlorinated organic solvents in Taiwan. AN - 73244625; 12725467 AB - We initiated an investigation to examine the possible association between the cancer risk and the chlorinated organic solvents exposure in an electronic factory. To obtain information on the incidence of the various types of cancer among the exposed and comparison groups, the cohort populations were merged with the National Mortality Database, the National Cancer Registry Database, and the National Insurance Hospitalization Database from the Department of Health (DOH), as well as the Labor Insurance Hospitalization Database from the Bureau of Labor Insurance (BLI). The proportionate cancer morbidity ratio (PCMR) was used to estimate the cancer risk of the exposed workers in comparison with either textile workers or electronics workers. After adjustment for age, only the PCMR for breast cancer in the exposed female employees was significantly elevated when compared with the two comparison groups. The increased risk of breast cancer was mainly found in the category of 1989-1997 for year of diagnosis when stratified by calendar year. However, there was no dose-response relationship between female breast cancer risk and duration of employment. Although some PCMRs for the cancers were also increased in the exposed group, female breast cancer was consistently increased when compared with both textile and electronics comparison groups using different exclusion criteria. The results obtained in the present study suggest a possible association between exposure to chlorinated organic solvents and female breast cancer. Since this association has never been reported in the previous studies, further study is needed to clarify the association. JF - Industrial health AU - Chang, Yung-Ming AU - Tai, Chi-Fu AU - Lin, Ruey S AU - Yang, Sweo-Chung AU - Chen, Chiou-Jong AU - Shih, Tung-Sheng AU - Liou, Saou-Hsing AD - Graduate Institute of Life Sciences, National Defense Medical Center, 161 Ming-Chun East Road, Sec. 6, Nei-Hu, Taipei, Taiwan, 114, ROC. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 77 EP - 87 VL - 41 IS - 2 SN - 0019-8366, 0019-8366 KW - Hydrocarbons, Chlorinated KW - 0 KW - Solvents KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Morbidity KW - Adult KW - Cohort Studies KW - Taiwan -- epidemiology KW - Epidemiological Monitoring KW - Middle Aged KW - Textile Industry KW - Electronics KW - Time Factors KW - Sex Distribution KW - Female KW - Male KW - Occupational Exposure -- statistics & numerical data KW - Neoplasms -- classification KW - Hydrocarbons, Chlorinated -- analysis KW - Solvents -- analysis KW - Neoplasms -- epidemiology KW - Occupational Diseases -- epidemiology KW - Occupational Diseases -- classification KW - Environmental Monitoring -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73244625?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Industrial+health&rft.atitle=A+proportionate+cancer+morbidity+ratio+study+of+workers+exposed+to+chlorinated+organic+solvents+in+Taiwan.&rft.au=Chang%2C+Yung-Ming%3BTai%2C+Chi-Fu%3BLin%2C+Ruey+S%3BYang%2C+Sweo-Chung%3BChen%2C+Chiou-Jong%3BShih%2C+Tung-Sheng%3BLiou%2C+Saou-Hsing&rft.aulast=Chang&rft.aufirst=Yung-Ming&rft.date=2003-04-01&rft.volume=41&rft.issue=2&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Industrial+health&rft.issn=00198366&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-23 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - GeneChip analysis of signaling pathways effected by nickel. AN - 73243753; 12729255 AB - The carcinogenicity of nickel compounds has been shown in numerous epidemiological and animal studies. Carcinogenesis is generally considered as a multistep accumulation of genetic alterations. Nickel, however, being highly carcinogenic is only a weak mutagen. We hypothesize that nickel may act by modulating signaling pathways, and subsequently by reprogramming transcription factors. Insoluble nickel is considered to be more carcinogenic than soluble. In this study using GeneChip technology we compared changes in gene expression caused by soluble and insoluble nickel compounds. We found that both soluble and insoluble nickel compounds induce similar signaling pathways following 20 h of in vitro exposure. For example, both nickel compounds activated a number of transcription factors including hypoxia-inducible factor I (HIF-1) and p53. The induction of these important transcription factors exerts potent selective pressure leading to cell transformation. The obtained data are in agreement with our previous observations that acute nickel exposure activates HIF-1 and p53 transcription factors and in nickel-transformed cells, the ratio of HIF-I activity to p53 activity was shifted towards high HIF-I activity. The activation of the same signaling pathways by soluble and insoluble nickel compounds suggested that both nickel compounds have similar carcinogenic potential in vitro. JF - Journal of environmental monitoring : JEM AU - Salnikow, Konstantin AU - Davidson, Todd AU - Kluz, Thomas AU - Chen, Haobin AU - Zhou, Daoji AU - Costa, Max AD - Nelson Institute of Environmental Medicine, NYU/NIEHS Center of Excellence, The NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. salnikow@env.med.nyu.edu Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 206 EP - 209 VL - 5 IS - 2 SN - 1464-0325, 1464-0325 KW - Transcription Factors KW - 0 KW - Tumor Suppressor Protein p53 KW - Nickel KW - 7OV03QG267 KW - Index Medicus KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Animals KW - Solubility KW - Neoplasms -- physiopathology KW - Cell Culture Techniques KW - Mice KW - Embryo, Mammalian KW - Signal Transduction KW - Fibroblasts KW - Gene Expression Profiling KW - Oligonucleotide Array Sequence Analysis KW - Nickel -- adverse effects KW - Nickel -- chemistry KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73243753?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+environmental+monitoring+%3A+JEM&rft.atitle=GeneChip+analysis+of+signaling+pathways+effected+by+nickel.&rft.au=Salnikow%2C+Konstantin%3BDavidson%2C+Todd%3BKluz%2C+Thomas%3BChen%2C+Haobin%3BZhou%2C+Daoji%3BCosta%2C+Max&rft.aulast=Salnikow&rft.aufirst=Konstantin&rft.date=2003-04-01&rft.volume=5&rft.issue=2&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=Journal+of+environmental+monitoring+%3A+JEM&rft.issn=14640325&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-15 N1 - Date created - 2003-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Changes in global gene and protein expression during early mouse liver carcinogenesis induced by non-genotoxic model carcinogens oxazepam and Wyeth-14,643. AN - 73242077; 12727805 AB - We hypothesized that the mouse liver tumor response to non-genotoxic carcinogens would involve some common early gene and protein expression changes that could ultimately be used to predict chemical hepatocarcinogenesis. In order to identify a panel of genes to test, we analyzed global differences in gene and protein expression in livers from B6C3F1 mice following dietary treatment with two rodent carcinogens, the benzodiazepine anti-anxiety drug oxazepam (2500 p.p.m.) and the hypolipidemic agent Wyeth (Wy)-14,643 (500 p.p.m.) compared with livers from untreated mice. Male mice were exposed for 2 weeks and 1, 3 or 6 months to oxazepam or Wy-14,643 in an age-matched study design. By histopathological evaluation, no liver preneoplastic foci or tumors were detected at 6 months in treated or control groups. By cDNA microarray analysis [NIEHS Mouse Chip (8700 genes); n = 3 individual livers/group, four hybridizations/sample], expression of 36 genes or 220 genes were changed relative to control livers following 6 months of oxazepam or Wy-14,643 treatment, respectively. To obtain a more comprehensive picture of gene/protein expression changes, we also conducted a proteomics study by 2D-gel electrophoresis followed by matrix assisted laser desorption/ionization-mass spectrometry on cytoplasmic, nuclear, and microsomal subcellular fractions of the same liver samples utilized for the cDNA microarray analysis. Real-time PCR, western blot analysis and immunohistochemistry were utilized for validation and to expand the results to other time points. Cyp2b20, growth arrest- and damage-inducible gene beta (Gadd45beta), tumor necrosis factor alpha-induced protein 2 and insulin-like growth factor binding protein 1 (Igfbp5) genes and proteins were upregulated by oxazepam, and Cyp2b20, Cyclin D1, proliferating cell nuclear antigen, Igfbp5, Gadd45beta and cell death-inducing DNA fragmentation factor alpha subunit-like effector A exhibited higher expression after Wy-14,643 treatment. Most of these genes/proteins were also deregulated at 2 weeks. There appeared to be more distinct than common changes in the expression of carcinogenesis-related genes/proteins between the two compounds, suggesting that the major carcinogenic pathways are different for these compounds and may be distinct for different chemical classes. JF - Carcinogenesis AU - Iida, Mari AU - Anna, Colleen H AU - Hartis, Jennifer AU - Bruno, Maribel AU - Wetmore, Barbara AU - Dubin, Joshua R AU - Sieber, Stella AU - Bennett, Lee AU - Cunningham, Michael L AU - Paules, Richard S AU - Tomer, Kenneth B AU - Houle, Christopher D AU - Merrick, Alex B AU - Sills, Robert C AU - Devereux, Theodora R AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 757 EP - 770 VL - 24 IS - 4 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA Primers KW - Pyrimidines KW - Oxazepam KW - 6GOW6DWN2A KW - pirinixic acid KW - 86C4MRT55A KW - Index Medicus KW - Polymerase Chain Reaction KW - Animals KW - Base Sequence KW - Mice KW - Male KW - Liver Neoplasms, Experimental -- genetics KW - Oxazepam -- toxicity KW - Pyrimidines -- toxicity KW - Liver Neoplasms, Experimental -- chemically induced KW - Gene Expression Regulation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73242077?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Changes+in+global+gene+and+protein+expression+during+early+mouse+liver+carcinogenesis+induced+by+non-genotoxic+model+carcinogens+oxazepam+and+Wyeth-14%2C643.&rft.au=Iida%2C+Mari%3BAnna%2C+Colleen+H%3BHartis%2C+Jennifer%3BBruno%2C+Maribel%3BWetmore%2C+Barbara%3BDubin%2C+Joshua+R%3BSieber%2C+Stella%3BBennett%2C+Lee%3BCunningham%2C+Michael+L%3BPaules%2C+Richard+S%3BTomer%2C+Kenneth+B%3BHoule%2C+Christopher+D%3BMerrick%2C+Alex+B%3BSills%2C+Robert+C%3BDevereux%2C+Theodora+R&rft.aulast=Iida&rft.aufirst=Mari&rft.date=2003-04-01&rft.volume=24&rft.issue=4&rft.spage=757&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-19 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of gammaherpesvirus-related neoplastic disorders in the immunosuppressed host. AN - 73225836; 12704593 AB - Neoplastic disease is a frequent complication in patients with acquired immunodeficiency disease (AIDS) and other immunodeficiencies. Many such neoplasms are caused by either Epstein-Barr virus (EBV) or Kaposi's sarcoma-associated herpes virus (KSHV). The treatment of such patients can be challenging. At the same time, the viral origin of these tumors offers targets to develop pathogenesis-based therapies. Standard therapies for these diseases involve such approaches as treating the underlying immunodeficiency, cytotoxic chemotherapy, and immunologic antitumor therapy. Novel therapy approaches include specific immune therapy and anti-angiogenesis approaches, now under development. JF - Seminars in hematology AU - Little, Richard F AU - Yarchoan, Robert AD - HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 163 EP - 171 VL - 40 IS - 2 SN - 0037-1963, 0037-1963 KW - Index Medicus KW - Tumor Virus Infections -- virology KW - Gammaherpesvirinae KW - Humans KW - Tumor Virus Infections -- chemically induced KW - Tumor Virus Infections -- complications KW - Lymphoproliferative Disorders -- etiology KW - Herpesviridae Infections -- chemically induced KW - Lymphoproliferative Disorders -- virology KW - Immunocompromised Host KW - Lymphoproliferative Disorders -- therapy KW - Herpesviridae Infections -- complications KW - Herpesviridae Infections -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73225836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+hematology&rft.atitle=Treatment+of+gammaherpesvirus-related+neoplastic+disorders+in+the+immunosuppressed+host.&rft.au=Little%2C+Richard+F%3BYarchoan%2C+Robert&rft.aulast=Little&rft.aufirst=Richard&rft.date=2003-04-01&rft.volume=40&rft.issue=2&rft.spage=163&rft.isbn=&rft.btitle=&rft.title=Seminars+in+hematology&rft.issn=00371963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-05 N1 - Date created - 2003-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TCDD-mediated alterations in the AhR-dependent pathway in Seveso, Italy, 20 years after the accident. AN - 73225021; 12727795 AB - Approximately 20 years after the Seveso, Italy, accident we conducted a population-based study to evaluate the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on cancer using mechanistically based biomarkers of dioxin response in humans. TCDD toxic effects are mediated by the aryl hydrocarbon receptor (AhR). We studied the AhR-dependent pathway in lymphocytes from 62 subjects randomly sampled from the highest exposed zones and 59 subjects from the surrounding non-contaminated area, frequency matched for age, gender and smoking. To our knowledge, this is the most comprehensive investigation to date designed to evaluate the key genes in the pathway, including AhR, aryl hydrocarbon receptor nuclear translocator, CYP1A1 and CYP1B1 transcripts and CYP1A1-associated 7-ethoxyresorufin O-deethylase (EROD) activity in a population heavily exposed to dioxin. Current lipid-adjusted plasma TCDD concentrations in these subjects ranged from 3.5 to 90 ng/kg (or p.p.t.) and were negatively associated with AhR mRNA in unstimulated peripheral blood mononuclear cells (P = 0.03). When mitogen-induced lymphocytes were cultured with 10 nM TCDD, all AhR-dependent genes were induced 1.2- to 13-fold. In these cells, plasma TCDD was associated with decreased EROD activity. In addition, there was a strong positive correlation between AhR and CYP1A1 expression (P = 0.001) and between AhR and CYP1B1 expression (P = 0.006). CYP1A1 expression was also strongly correlated with EROD activity (P = 0.001). The analysis of the expression of dioxin-inducible genes involved in carcinogenesis may help in determining dose-response relationships for human exposure to dioxin in vivo and in assessing the variability of human response, which may indicate the presence of subjects more susceptible to disease as a result of such exposures. JF - Carcinogenesis AU - Landi, Maria Teresa AU - Bertazzi, Pier Alberto AU - Baccarelli, Andrea AU - Consonni, Dario AU - Masten, Scott AU - Lucier, George AU - Mocarelli, Paolo AU - Needham, Larry AU - Caporaso, Neil AU - Grassman, Jean AD - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892-7236, USA. landim@mail.nih.gov Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 673 EP - 680 VL - 24 IS - 4 SN - 0143-3334, 0143-3334 KW - ARNT protein, human KW - 0 KW - DNA Primers KW - DNA-Binding Proteins KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - Transcription Factors KW - Aryl Hydrocarbon Receptor Nuclear Translocator KW - 138391-32-9 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP1B1 protein, human KW - Cytochrome P-450 CYP1A1 KW - Cytochrome P-450 CYP1B1 KW - Index Medicus KW - Cytochrome P-450 CYP1A1 -- genetics KW - Transcription Factors -- metabolism KW - Humans KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Messenger -- genetics KW - Transcription Factors -- genetics KW - Italy KW - Aryl Hydrocarbon Hydroxylases -- metabolism KW - Base Sequence KW - Case-Control Studies KW - Aryl Hydrocarbon Hydroxylases -- genetics KW - Polychlorinated Dibenzodioxins -- adverse effects KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73225021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=TCDD-mediated+alterations+in+the+AhR-dependent+pathway+in+Seveso%2C+Italy%2C+20+years+after+the+accident.&rft.au=Landi%2C+Maria+Teresa%3BBertazzi%2C+Pier+Alberto%3BBaccarelli%2C+Andrea%3BConsonni%2C+Dario%3BMasten%2C+Scott%3BLucier%2C+George%3BMocarelli%2C+Paolo%3BNeedham%2C+Larry%3BCaporaso%2C+Neil%3BGrassman%2C+Jean&rft.aulast=Landi&rft.aufirst=Maria&rft.date=2003-04-01&rft.volume=24&rft.issue=4&rft.spage=673&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-19 N1 - Date created - 2003-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of chromatin damage in nickel-induced carcinogenesis. A review of recent developments. AN - 73224233; 12729250 AB - Over the last years, we have been testing a hypothesis that molecular mechanisms of nickel-induced carcinogenesis include interactions of this metal with major chromatin components; DNA, histones, and protamines. Our investigations using synthetic peptide models have resulted in identification of nickel-binding sites in core histones H3 and H2A and in protamine P2. These are: the internal -Cys110-AIH- motif in histone H3: the C-terminal-E121-SHHKAKGK "tail" motif in histone H2A; and the N-terminal RTH- motif in protamine P2. Ni(II) bound to the H3 and P2 motifs enhances oxidative DNA base damage by H2O2. In contrast, Ni(II) complex with the H2A "tail" is not redox active. However, at pH 7.4, it undergoes hydrolysis yielding a new complex, Ni(II)-SHHKAKGK, reactive with H2O2 and capable of mediating DNA oxidation. The "tail" cutting of H2A has also been observed in cells cultured with Ni(II). In Ni(II) complex with the protamine P2 peptides, H2O2 causes degradation of the metal-binding His3 and the distant Tyr8 residues. This site-specificity results from a long-range structuring effect of Ni(II) on its protamine ligand. In conclusion, Ni(II) binding to some chromatin proteins in somatic and sperm cells may result in oxidative and structural damage to the proteins and DNA. These effects may alter the fidelity of DNA replication and gene expression and thus facilitate carcinogenesis, including paternally-mediated cancer in the progeny. JF - Journal of environmental monitoring : JEM AU - Kasprzak, Kazimierz S AU - Bal, Wojciech AU - Karaczyn, Aldona A AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Bldg. 538, Room 205E, Frederick, MD 21702, USA. kasprkaz@mail.ncifcrf.gov Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 183 EP - 187 VL - 5 IS - 2 SN - 1464-0325, 1464-0325 KW - Chromatin KW - 0 KW - DNA Adducts KW - Histones KW - Protamines KW - Nickel KW - 7OV03QG267 KW - Index Medicus KW - Humans KW - DNA Damage KW - Chromatin -- drug effects KW - Nickel -- adverse effects KW - Chromatin -- physiology KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73224233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+environmental+monitoring+%3A+JEM&rft.atitle=The+role+of+chromatin+damage+in+nickel-induced+carcinogenesis.+A+review+of+recent+developments.&rft.au=Kasprzak%2C+Kazimierz+S%3BBal%2C+Wojciech%3BKaraczyn%2C+Aldona+A&rft.aulast=Kasprzak&rft.aufirst=Kazimierz&rft.date=2003-04-01&rft.volume=5&rft.issue=2&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Journal+of+environmental+monitoring+%3A+JEM&rft.issn=14640325&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-07-15 N1 - Date created - 2003-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the toxicity, mutagenicity, and carcinogenicity of methacrylonitrile in F344 Rats and B6C3F1 mice. AN - 73201016; 12698239 AB - Methacrylonitrile is an unsaturated aliphatic nitrile. It is widely used in the preparation of homopolymers and copolymers, elastomers, and plastics, and as a chemical intermediate in the preparation of acids, amides, amines, esters, and other nitriles. Methacrylonitrile was nominated for study by the National Cancer Institute (USA) because of the potential for human exposure, structural similarity to the known carcinogen acrylonitrile, and a lack of toxicity and carcinogenicity data. Doses selected for the 2-year study were based on the results of the 13-week gavage studies. Groups of 50 male and 50 female animals were exposed by gavage to 0, 3, 10, or 30 mg/kg in F344 rats, and 0, 1.5, 3 or 6 mg/kg in B6C3F1 mice, 5 days per week for 2 years. Urinary excretion of N-acetyl- S-(2-cyanopropyl)- l-cysteine (NACPC) and N-acetyl- S-(2-hydroxypropyl)- l-cysteine (NAHPC) were measured as markers of exposure at various time points after methacrylonitrile administration, and demonstrated that exposure of animals to methacrylonitrile occurred as intended. Urinary excretion of NACPC and NAHPC increased in rats and mice in a dose-dependent manner. In contrast to observations in rats, the ratios of NACPC/creatinine were generally higher in female than in male mice. Further, the ratios of NAHPC/creatinine in rats were significantly greater at all time points and all doses than the corresponding ratios of NACPC/creatinine in male and female mice. In both rats and mice, survival was not affected by treatment. In rats, mean body weights of the 30 mg/kg groups were less than those of the vehicle controls after weeks 21 and 37 for males and females, respectively. No treatment-related effect on body weight was seen in mice. There were no neoplasms (in either species) or non-neoplastic lesions (mice only) that were attributed to methacrylonitrile administration. In rats, the incidences of olfactory epithelial atrophy and metaplasia of the nose were significantly greater in 30 mg/kg males and females than those in the vehicle controls. Increased incidences of cytoplasmic vacuolation occurred in the liver of males and females. Testing methacrylonitrile in a battery of short-term in vitro and in vivo tests showed no evidence of genotoxicity. In conclusion, under the conditions of these 2-year gavage studies, there was no evidence of a carcinogenic activity of methacrylonitrile in male or female F344/N rats or B6C3F1 mice. Methacrylonitrile-related non-neoplastic lesions were seen in the nose and liver of rats. JF - Archives of toxicology AU - Nyska, Abraham AU - Ghanayem, Burhan I AD - Laboratory of Experimental Pathology, MD B3-06, Environmental Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA. nyska@niehs.nih.gov Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 233 EP - 242 VL - 77 IS - 4 SN - 0340-5761, 0340-5761 KW - Biomarkers KW - 0 KW - Carcinogens KW - Methacrylates KW - Mutagens KW - Nitriles KW - methacrylonitrile KW - 04S4K38612 KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Administration, Oral KW - Animals KW - Liver -- pathology KW - Creatinine -- urine KW - Vacuoles -- pathology KW - Dose-Response Relationship, Drug KW - Olfactory Mucosa -- pathology KW - Mice KW - Cytoplasm -- drug effects KW - Cytoplasm -- pathology KW - Rats KW - Mice, Inbred Strains KW - Vacuoles -- drug effects KW - Rats, Inbred F344 KW - Liver -- drug effects KW - Biomarkers -- analysis KW - Body Weight -- drug effects KW - Toxicity Tests KW - Female KW - Male KW - Olfactory Mucosa -- drug effects KW - Methacrylates -- toxicity KW - Nitriles -- administration & dosage KW - Environmental Exposure KW - Carcinogens -- toxicity KW - Nitriles -- metabolism KW - Mutagens -- toxicity KW - Methacrylates -- metabolism KW - Nitriles -- toxicity KW - Methacrylates -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73201016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+toxicology&rft.atitle=Characterization+of+the+toxicity%2C+mutagenicity%2C+and+carcinogenicity+of+methacrylonitrile+in+F344+Rats+and+B6C3F1+mice.&rft.au=Nyska%2C+Abraham%3BGhanayem%2C+Burhan+I&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=2003-04-01&rft.volume=77&rft.issue=4&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Archives+of+toxicology&rft.issn=03405761&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-22 N1 - Date created - 2003-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bone marrow-derived, endothelial progenitor-like cells as angiogenesis-selective gene-targeting vectors. AN - 73191627; 12692593 AB - Human and mouse proliferation-competent, bone marrow or peripheral circulation derived endothelial progenitor-like cells (EPCs) were isolated, expanded and genetically engineered ex vivo to express the beta galactosidase (beta-gal), green fluorescence protein or thymidine kinase (TK) genes using retrovirus-mediated gene transfer. Genetically labeled EPCs were transplanted into sublethally irradiated tumor-bearing mice and were found to migrate to and incorporate into the angiogenic vasculature of growing tumors while maintaining transgene expression. Ganciclovir treatment resulted in significant tumor necrosis in animals previously administered TK-expressing EPCs with no systemic toxicity. These results demonstrate the feasibility of using genetically modified EPCs as angiogenesis-selective gene-targeting vectors and the potential of this approach to mediate non-toxic and systemic antitumor responses. JF - Gene therapy AU - Ferrari, N AU - Glod, J AU - Lee, J AU - Kobiler, D AU - Fine, H A AD - Neuro-Oncology Branch, National Cancer Institute, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 647 EP - 656 VL - 10 IS - 8 SN - 0969-7128, 0969-7128 KW - Antigens, CD34 KW - 0 KW - Antiviral Agents KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Ganciclovir KW - P9G3CKZ4P5 KW - Index Medicus KW - Cell Movement KW - Antiviral Agents -- therapeutic use KW - Animals KW - Mice, Mutant Strains KW - Ganciclovir -- therapeutic use KW - Antigens, CD34 -- immunology KW - Mice KW - Neovascularization, Pathologic KW - Thymidine Kinase -- genetics KW - Genetic Vectors -- administration & dosage KW - Gene Targeting -- methods KW - Endothelium, Vascular -- cytology KW - Genetic Therapy -- methods KW - Neoplasms -- therapy KW - Endothelium, Vascular -- immunology KW - Bone Marrow Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73191627?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Bone+marrow-derived%2C+endothelial+progenitor-like+cells+as+angiogenesis-selective+gene-targeting+vectors.&rft.au=Ferrari%2C+N%3BGlod%2C+J%3BLee%2C+J%3BKobiler%2C+D%3BFine%2C+H+A&rft.aulast=Ferrari&rft.aufirst=N&rft.date=2003-04-01&rft.volume=10&rft.issue=8&rft.spage=647&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 - 2003-06-06 N1 - Date created - 2003-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Double blind placebo-controlled trial of pleconaril in infants with enterovirus meningitis. AN - 73191185; 12690273 AB - Enterovirus (EV) meningitis is common in infants and may have neurologic complications. Treatment of older children and adults with pleconaril has been associated with reduced severity and duration of symptoms. This study evaluated the pharmacokinetics, safety and efficacy of pleconaril in infants with EV meningitis. Infants < or =12 months old with suspected EV meningitis were randomized 2:1 to receive pleconaril, 5 mg/kg/dose orally three times a day or placebo for 7 days. Evaluations included pharmacokinetic determinations, safety laboratory testing, serial culture and PCR assays and clinical evaluations. Of 21 evaluable subjects 20 were confirmed with EV infection (12 pleconaril, 8 placebo). Among pleconaril-treated subjects 26 of 29 peak and trough pleconaril levels exceeded the 90% inhibitory concentration for EVs. A median 3.5-fold drug accumulation occurred between Days 2 and 7. Pleconaril was well-tolerated, although twice as many adverse events occurred per subject in the pleconaril group. Serial cultures from the oropharynx, rectum and serum had low yield ( or =50%) persisting through Day 14. No significant differences in duration of positivity by culture or PCR, hospitalization or symptoms were detected between groups. The dose of pleconaril studied provided sufficient plasma levels and was well-tolerated; however, drug accumulation was evident. The low yields of serial viral cultures, relatively short and benign clinical courses and the small number of subjects enrolled precluded demonstration of efficacy. If this medication is to be prescribed in infants, surveillance for toxicity related to drug accumulation will be necessary. JF - The Pediatric infectious disease journal AU - Abzug, Mark J AU - Cloud, Gretchen AU - Bradley, John AU - Sánchez, Pablo J AU - Romero, José AU - Powell, Dwight AU - Lepow, Martha AU - Mani, Chitra AU - Capparelli, Edmund V AU - Blount, Sharon AU - Lakeman, Fred AU - Whitley, Richard J AU - Kimberlin, David W AU - National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group AD - Pediatric Infectious Disease, Department of Pediatrics, University of Colorado School of Medicine and The Children's Hospital, 1056 E. Nineteenth Avenue, Denver, CO 80218, USA. abzug.mark@tchden.org ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 335 EP - 341 VL - 22 IS - 4 SN - 0891-3668, 0891-3668 KW - Oxadiazoles KW - 0 KW - pleconaril KW - 9H4570Q89D KW - Index Medicus KW - Severity of Illness Index KW - Administration, Oral KW - Probability KW - Drug Administration Schedule KW - Reference Values KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Risk Assessment KW - Biological Availability KW - Infant KW - Treatment Outcome KW - Follow-Up Studies KW - Female KW - Male KW - Enterovirus Infections -- drug therapy KW - Meningitis, Viral -- drug therapy KW - Oxadiazoles -- pharmacokinetics KW - Oxadiazoles -- administration & dosage KW - Enterovirus Infections -- diagnosis KW - Meningitis, Viral -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73191185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Pediatric+infectious+disease+journal&rft.atitle=Double+blind+placebo-controlled+trial+of+pleconaril+in+infants+with+enterovirus+meningitis.&rft.au=Abzug%2C+Mark+J%3BCloud%2C+Gretchen%3BBradley%2C+John%3BS%C3%A1nchez%2C+Pablo+J%3BRomero%2C+Jos%C3%A9%3BPowell%2C+Dwight%3BLepow%2C+Martha%3BMani%2C+Chitra%3BCapparelli%2C+Edmund+V%3BBlount%2C+Sharon%3BLakeman%2C+Fred%3BWhitley%2C+Richard+J%3BKimberlin%2C+David+W%3BNational+Institute+of+Allergy+and+Infectious+Diseases+Collaborative+Antiviral+Study+Group&rft.aulast=Abzug&rft.aufirst=Mark&rft.date=2003-04-01&rft.volume=22&rft.issue=4&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=The+Pediatric+infectious+disease+journal&rft.issn=08913668&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-04 N1 - Date created - 2003-04-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Curr Neurol Neurosci Rep. 2003 Nov;3(6):459-60 [14565898] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential responses of stress genes to low dose-rate gamma irradiation. AN - 73188769; 12692264 AB - In the past, most mechanistic studies of ionizing radiation response have employed very large doses, then extrapolated the results down to doses relevant to human exposure. It is becoming increasingly apparent, however, that this does not give an accurate or complete picture of the effects of most environmental exposures, which tend to be of low dose and protracted over time. We have initiated direct studies of low dose exposures, and using the relatively responsive ML-1 cell line, have shown that changes in gene expression can be triggered by doses of gamma-rays of 10 cGy and less in human cells. We have now extended these studies to investigate the effects on gene induction of reducing the rate of irradiation. In the ML-1 human myeloid leukemia cell line, we have found that reducing the dose rate over three orders of magnitude results in some protection against the induction of apoptosis, but still causes linear induction of the p53-regulated genes CDKN1A, GADD45A, and MDM2 between 2 and 50 cGy. Reducing the rate of exposure reduces the magnitude of induction of CDKN1A and GADD45A, but not the magnitude or duration of cell cycle delay. In contrast, MDM2 is induced to the same extent regardless of the rate of dose delivery. Microarray analysis has identified additional low dose-rate-inducible genes, and indicates the existence of two general classes of low dose-rate responders in ML-1. One group of genes is induced in a dose rate-dependent fashion, similar to GADD45A and CDKN1A. Functional annotation of this gene cluster indicates a preponderance of genes with known roles in apoptosis regulation. Similarly, a group of genes with dose rate-independent induction, such as seen for MDM2, was also identified. The majority of genes in this group are involved in cell cycle regulation. This apparent differential regulation of stress signaling pathways and outcomes in response to protracted radiation exposure has implications for carcinogenesis and risk assessment, and could not have been predicted from classical high dose studies. JF - Molecular cancer research : MCR AU - Amundson, Sally A AU - Lee, Richard Anthony AU - Koch-Paiz, Christine A AU - Bittner, Michael L AU - Meltzer, Paul AU - Trent, Jeffrey M AU - Fornace, Albert J AD - Division of Basic Science, National Cancer Institute and National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA. amundson@box-a.nih.gov Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 445 EP - 452 VL - 1 IS - 6 SN - 1541-7786, 1541-7786 KW - CDKN1A protein, human KW - 0 KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - GADD45A protein, human KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - Index Medicus KW - Nuclear Proteins -- genetics KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Apoptosis -- radiation effects KW - Cell Line, Tumor KW - Dose-Response Relationship, Radiation KW - Transcriptional Activation KW - Apoptosis -- genetics KW - Cyclins -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - Cell Cycle -- genetics KW - Cell Cycle -- radiation effects KW - Nuclear Proteins -- metabolism KW - Time Factors KW - Cyclins -- genetics KW - Gene Expression Profiling KW - Gamma Rays KW - Gene Expression Regulation, Neoplastic -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73188769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cancer+research+%3A+MCR&rft.atitle=Differential+responses+of+stress+genes+to+low+dose-rate+gamma+irradiation.&rft.au=Amundson%2C+Sally+A%3BLee%2C+Richard+Anthony%3BKoch-Paiz%2C+Christine+A%3BBittner%2C+Michael+L%3BMeltzer%2C+Paul%3BTrent%2C+Jeffrey+M%3BFornace%2C+Albert+J&rft.aulast=Amundson&rft.aufirst=Sally&rft.date=2003-04-01&rft.volume=1&rft.issue=6&rft.spage=445&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+research+%3A+MCR&rft.issn=15417786&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-04-15 N1 - Date created - 2003-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of disulfide bonds in the assembly and function of MD-2. AN - 73159112; 12642668 AB - MD-2 is a secreted glycoprotein that binds to the extracellular domain of Toll-like receptor 4 (TLR4) and is required for the activation of TLR4 by lipopolysaccharide (LPS). The protein contains seven Cys residues and consists of a heterogeneous collection of disulfide-linked oligomers. To investigate the role of sulfhydryls in MD-2 structure and function, we created 17 single and multiple Cys substitution mutants. All of the MD-2 mutant proteins, including one totally lacking Cys residues, were secreted and stable. SDSPAGE analyses indicated that most Cys residues could participate in oligomer formation and that no single Cys residue was required for oligomerization. Of the single Cys substitutions, only C95S and C105S failed to confer LPS responsiveness on TLR4 when mutant and TLR4 were cotransfected into cells expressing an NF-kappaB reporter plasmid. Surprisingly, substitution of both C95 and C105 partially restored activity. Structural analyses revealed that C95 and C105 formed an intrachain disulfide bond, whereas C95 by itself produced an inactive dimer. In contrast to the cotransfection experiments, only WT MD-2 conferred responsiveness to LPS when secreted proteins were added directly to TLR4 reporter cells. Our data are consistent with a model in which most, possibly all sulfhydryls lie on the surface of a stable MD-2 core structure where they form both intra- and interchain disulfide bridges. These disulfide bonds produce a heterogeneous array of oligomers, including some species that can form an active complex with TLR4. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Mullen, Gregory E D AU - Kennedy, Margaret N AU - Visintin, Alberto AU - Mazzoni, Alessandra AU - Leifer, Cynthia A AU - Davies, David R AU - Segal, David M AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360, USA. Y1 - 2003/04/01/ PY - 2003 DA - 2003 Apr 01 SP - 3919 EP - 3924 VL - 100 IS - 7 SN - 0027-8424, 0027-8424 KW - Antigens, Surface KW - 0 KW - Disulfides KW - LY96 protein, human KW - Lymphocyte Antigen 96 KW - NF-kappa B KW - Recombinant Proteins KW - Serine KW - 452VLY9402 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Humans KW - Genetic Vectors KW - Kidney KW - Recombinant Proteins -- chemistry KW - Cell Line KW - Amino Acid Substitution KW - NF-kappa B -- metabolism KW - Antigens, Surface -- chemistry KW - Disulfides -- analysis KW - Antigens, Surface -- metabolism KW - Disulfides -- metabolism KW - Antigens, Surface -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73159112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+role+of+disulfide+bonds+in+the+assembly+and+function+of+MD-2.&rft.au=Mullen%2C+Gregory+E+D%3BKennedy%2C+Margaret+N%3BVisintin%2C+Alberto%3BMazzoni%2C+Alessandra%3BLeifer%2C+Cynthia+A%3BDavies%2C+David+R%3BSegal%2C+David+M&rft.aulast=Mullen&rft.aufirst=Gregory+E&rft.date=2003-04-01&rft.volume=100&rft.issue=7&rft.spage=3919&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 - 2003-05-22 N1 - Date created - 2003-04-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 2001 Sep 15;167(6):3354-9 [11544325] J Endotoxin Res. 2000;6(5):401-5 [11521063] J Biol Chem. 2001 Oct 12;276(41):38044-51 [11500507] Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12156-61 [11593030] Int Immunol. 2001 Dec;13(12):1595-9 [11717200] J Biol Chem. 2002 Jan 18;277(3):1845-54 [11706042] Nat Rev Immunol. 2001 Nov;1(2):135-45 [11905821] Biochem Biophys Res Commun. 2002 Apr 12;292(4):880-5 [11944896] Infect Immun. 2002 Jul;70(7):3546-50 [12065494] J Biol Chem. 2002 Jun 28;277(26):23427-32 [11976338] Nat Immunol. 2002 Jul;3(7):667-72 [12055629] J Leukoc Biol. 1998 Jul;64(1):25-32 [9665271] Science. 1998 Dec 11;282(5396):2085-8 [9851930] J Biol Chem. 1999 Apr 16;274(16):10689-92 [10196138] J Immunol. 1999 Apr 1;162(7):3749-52 [10201887] J Exp Med. 1999 Jun 7;189(11):1777-82 [10359581] Science. 1999 Dec 3;286(5446):1882-8 [10583943] Science. 1999 Dec 3;286(5446):1888-93 [10583944] J Biol Chem. 2001 Jun 15;276(24):21129-35 [11274165] Trends Cell Biol. 2001 Jul;11(7):304-11 [11413042] J Exp Med. 2001 Jul 2;194(1):79-88 [11435474] Nat Immunol. 2001 Aug;2(8):675-80 [11477402] J Endotoxin Res. 2001;7(3):232-6 [11581576] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of transgenic mouse models in carcinogen identification. AN - 73156874; 12676597 AB - In this article, we examine existing data on the use of transgenic mouse models for identification of human carcinogens. We focus on the three most extensively studied of these mice, Trp53+/-, Tg/AC, and RasH2, and compare their performance with the traditional 2-year rodent bioassay. Data on 99 chemicals were evaluated. Using the International Agency for Research on Cancer/Report on Carcinogens determinations for the carcinogenicity of these chemicals to humans as the standard for comparison, we evaluated a variety of potential testing strategies ranging from individual transgenic models to combinations of these three models with each other and with traditional rodent assays. The individual transgenic models made the "correct" determinations (positive for carcinogens; negative for noncarcinogens) for 74-81% of the chemicals, with an increase to as much as 83% using combined strategies (e.g., Trp53+/- for genotoxic chemicals and RasH2 for all chemicals). For comparison, identical analysis of chemicals in this data set that were tested in the 2-year, two-species rodent bioassay yielded correct determinations for 69% of the chemicals. However, although the transgenic models had a high percentage of correct determinations, they did miss a number of known or probable human carcinogens, whereas the bioassay missed none of these chemicals. Therefore, we also evaluated mixed strategies using transgenic models and the rat bioassay. These strategies yielded approximately 85% correct determinations, missed no carcinogens, and cut the number of positive determinations for human noncarcinogens in half. Overall, the transgenic models performed well, but important issues of validation and standardization need further attention to permit their regulatory acceptance and use in human risk assessment. JF - Environmental health perspectives AU - Pritchard, John B AU - French, John E AU - Davis, Barbara J AU - Haseman, Joseph K AD - Laboratory of Pharmacology and Chemistry, Environmental Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. pritchard@niehs.nih.gov Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 444 EP - 454 VL - 111 IS - 4 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Reference Values KW - Humans KW - Mice KW - Risk Assessment KW - Biological Assay -- methods KW - Genes, ras KW - Mutagenicity Tests KW - Genes, p53 KW - Neoplasms -- chemically induced KW - Drug Evaluation, Preclinical KW - Female KW - Male KW - Disease Models, Animal KW - Mice, Transgenic KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73156874?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=The+role+of+transgenic+mouse+models+in+carcinogen+identification.&rft.au=Pritchard%2C+John+B%3BFrench%2C+John+E%3BDavis%2C+Barbara+J%3BHaseman%2C+Joseph+K&rft.aulast=Pritchard&rft.aufirst=John&rft.date=2003-04-01&rft.volume=111&rft.issue=4&rft.spage=444&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - 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Last updated - 2017-01-18 ER - TY - JOUR T1 - Radical causes of cancer. AN - 73151987; 12671666 AB - Free radicals are ubiquitous in our body and are generated by normal physiological processes, including aerobic metabolism and inflammatory responses, to eliminate invading pathogenic microorganisms. Because free radicals can also inflict cellular damage, several defences have evolved both to protect our cells from radicals--such as antioxidant scavengers and enzymes--and to repair DNA damage. Understanding the association between chronic inflammation and cancer provides insights into the molecular mechanisms involved. In particular, we highlight the interaction between nitric oxide and p53 as a crucial pathway in inflammatory-mediated carcinogenesis. JF - Nature reviews. Cancer AU - Hussain, S Perwez AU - Hofseth, Lorne J AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, Maryland 20892-4255, USA. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 276 EP - 285 VL - 3 IS - 4 SN - 1474-175X, 1474-175X KW - Free Radicals KW - 0 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Index Medicus KW - Models, Animal KW - Animals KW - Genes, p53 KW - DNA Damage KW - Nitric Oxide Synthase -- genetics KW - Humans KW - Inflammation -- genetics KW - Inflammation -- metabolism KW - Chemoprevention KW - Mutation KW - Nitric Oxide Synthase -- biosynthesis KW - Neoplasms -- prevention & control KW - Free Radicals -- metabolism KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73151987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+reviews.+Cancer&rft.atitle=Radical+causes+of+cancer.&rft.au=Hussain%2C+S+Perwez%3BHofseth%2C+Lorne+J%3BHarris%2C+Curtis+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=2003-04-01&rft.volume=3&rft.issue=4&rft.spage=276&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Cancer&rft.issn=1474175X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-07 N1 - Date created - 2003-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutaredoxin is essential for maintenance of brain mitochondrial complex I: studies with MPTP. AN - 73148617; 12594173 AB - Mitochondrial complex I dysfunction is implicated in the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Identification of factors involved in maintenance and restoration of complex I function could potentially help to develop prophylactic and therapeutic strategies for treatment of this class of disorders. Down-regulation of glutaredoxin (thioltransferase, a thiol disulfide oxido-reductase) using antisense oligonucleotides results in the loss of mitochondrial complex I activity in mouse brain. 1-Methyl-4-phenyl-1,2,3,6,tetrahydro-pyridine (MPTP), the neurotoxin that causes Parkinson's disease-like symptoms in primates and dopaminergic cell loss in mice, acts through the inhibition of complex I. Regeneration of complex I activity in the striatum occurs concurrently with increase in glutaredoxin activity, 4 h after the neurotoxic insult, and is mediated through activation of activating protein-1. Down-regulation of glutaredoxin using anti-sense oligonucleotides prevents recovery of complex I in the striatum after MPTP treatment, providing support for the critical role for glutaredoxin in recovery of mitochondrial function in brain. Maintenance and restoration of protein thiol homeostasis by glutaredoxin may be important factors in preventing complex I dysfunction. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Kenchappa, Rajappa S AU - Ravindranath, Vijayalakshmi AD - Department of Neurochemistry, National Institute of Mental Health & Neurosciences, Bangalore, India. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 717 EP - 719 VL - 17 IS - 6 KW - Glutaredoxins KW - 0 KW - NF-kappa B KW - Oligonucleotides, Antisense KW - RNA, Messenger KW - Transcription Factors KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Oxidoreductases KW - EC 1.- KW - NADH, NADPH Oxidoreductases KW - EC 1.6.- KW - Electron Transport Complex I KW - EC 1.6.5.3 KW - Protein Disulfide Reductase (Glutathione) KW - EC 1.8.4.2 KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - Corpus Striatum -- metabolism KW - RNA, Messenger -- drug effects KW - Oligonucleotides, Antisense -- genetics KW - Mice KW - Oligonucleotides, Antisense -- pharmacology KW - RNA, Messenger -- genetics KW - Oxidation-Reduction KW - RNA, Messenger -- metabolism KW - Down-Regulation KW - Corpus Striatum -- drug effects KW - Gene Expression Regulation -- drug effects KW - Up-Regulation KW - NF-kappa B -- metabolism KW - Oxidoreductases -- genetics KW - Oxidoreductases -- metabolism KW - Brain -- drug effects KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - NADH, NADPH Oxidoreductases -- metabolism KW - Brain -- metabolism KW - Oxidoreductases -- drug effects KW - NADH, NADPH Oxidoreductases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73148617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glutaredoxin+is+essential+for+maintenance+of+brain+mitochondrial+complex+I%3A+studies+with+MPTP.&rft.au=Kenchappa%2C+Rajappa+S%3BRavindranath%2C+Vijayalakshmi&rft.aulast=Kenchappa&rft.aufirst=Rajappa&rft.date=2003-04-01&rft.volume=17&rft.issue=6&rft.spage=717&rft.isbn=&rft.btitle=&rft.title=FASEB+journal+%3A+official+publication+of+the+Federation+of+American+Societies+for+Experimental+Biology&rft.issn=1530-6860&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-21 N1 - Date created - 2003-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The National Children's Study of environmental effects on child health and development. AN - 73148564; 12676629 AB - Increasing recognition that children may be more susceptible than adults to environmental exposures and that they experience potentially life-long consequences of such exposures has led to widespread support for a large new cohort study in the United States. In this article, we propose a framework for a new cohort study of children, with follow-up beginning before birth and continuing to age 21 years. We also describe the administrative structure that has been built to develop the proposal further. The structure includes a partnership between federal and nonfederal scientists and relies on a collaborative, interdisciplinary research effort of unprecedented scale in medical research. We discuss briefly how the proposed cohort could be used to examine, among many other things, the effect of chemical contaminants in breast milk on children's health and development. JF - Environmental health perspectives AU - Branum, Amy M AU - Collman, Gwen W AU - Correa, Adolfo AU - Keim, Sarah A AU - Kessel, Woodie AU - Kimmel, Carole A AU - Klebanoff, Mark A AU - Longnecker, Matthew P AU - Mendola, Pauline AU - Rigas, Marc AU - Selevan, Sherry G AU - Scheidt, Peter C AU - Schoendorf, Kenneth AU - Smith-Khuri, Eleanor AU - Yeargin-Allsopp, Marshalyn AU - National Children's Study Interagency Coordinating Committee, Centers for Disease Control and Prevention AU - National Children's Study Interagency Coordinating Committee, National Institute of Environmental Health Sciences AU - National Children's Study Interagency Coordinating Committee, National Institute of Child Health and Human Development AU - National Children's Study Interagency Coordinating Committee, U.S. Environmental Protection Agency AD - Infant and Child Health Studies Branch, National Center for Health Studies, Centers for Disease Control and Prevention, Hyattsville, MD, USA. ; National Children's Study Interagency Coordinating Committee, Centers for Disease Control and Prevention ; National Children's Study Interagency Coordinating Committee, National Institute of Environmental Health Sciences ; National Children's Study Interagency Coordinating Committee, National Institute of Child Health and Human Development ; National Children's Study Interagency Coordinating Committee, U.S. Environmental Protection Agency Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 642 EP - 646 VL - 111 IS - 4 SN - 0091-6765, 0091-6765 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Infant KW - Milk, Human -- chemistry KW - Humans KW - Cohort Studies KW - Infant, Newborn KW - Child KW - Research Design KW - Child, Preschool KW - Environmental Exposure KW - Child Development KW - Child Welfare KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73148564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=The+National+Children%27s+Study+of+environmental+effects+on+child+health+and+development.&rft.au=Branum%2C+Amy+M%3BCollman%2C+Gwen+W%3BCorrea%2C+Adolfo%3BKeim%2C+Sarah+A%3BKessel%2C+Woodie%3BKimmel%2C+Carole+A%3BKlebanoff%2C+Mark+A%3BLongnecker%2C+Matthew+P%3BMendola%2C+Pauline%3BRigas%2C+Marc%3BSelevan%2C+Sherry+G%3BScheidt%2C+Peter+C%3BSchoendorf%2C+Kenneth%3BSmith-Khuri%2C+Eleanor%3BYeargin-Allsopp%2C+Marshalyn%3BNational+Children%27s+Study+Interagency+Coordinating+Committee%2C+Centers+for+Disease+Control+and+Prevention%3BNational+Children%27s+Study+Interagency+Coordinating+Committee%2C+National+Institute+of+Environmental+Health+Sciences%3BNational+Children%27s+Study+Interagency+Coordinating+Committee%2C+National+Institute+of+Child+Health+and+Human+Development%3BNational+Children%27s+Study+Interagency+Coordinating+Committee%2C+U.S.+Environmental+Protection+Agency&rft.aulast=Branum&rft.aufirst=Amy&rft.date=2003-04-01&rft.volume=111&rft.issue=4&rft.spage=642&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 - 2003-07-15 N1 - Date created - 2003-04-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Pediatr Res. 2001 Sep;50(3):331-6 [11518819] Public Health Rep. 2000 Nov-Dec;115(6):521-9 [11354334] Lancet. 2001 Nov 10;358(9293):1602-7 [11716887] Am J Med Sci. 2001 Nov;322(5):267-74 [11721800] Scand J Public Health. 2001 Dec;29(4):300-7 [11775787] J Pediatr. 2002 Jan;140(1):33-9 [11815761] J Pediatr. 2002 Jan;140(1):48-56 [11815763] Am J Public Health. 2002 Feb;92(2):231-4 [11818297] Pediatrics. 2002 Feb;109(2 Suppl):362-7 [11826251] Arch Orthop Trauma Surg. 2002 Mar;122(2):96-8 [11880910] Ment Retard Dev Disabil Res Rev. 2002;8(1):1-2 [11921379] J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900 [12084585] MMWR Surveill Summ. 2002 Mar 29;51(1):1-13 [12420904] JAMA. 2003 Jan 1;289(1):49-55 [12503976] Lancet. 1974 Jun 1;1(7866):1076-8 [4135246] J Pediatr. 1975 Oct;87(4):638-42 [1159596] N Engl J Med. 1976 Nov 4;295(19):1029-33 [972656] Am J Dis Child. 1976 Nov;130(11):1207-10 [984002] Residue Rev. 1983;89:1-128 [6316441] Paediatr Perinat Epidemiol. 1988 Jul;2(3):265-82 [3070486] N Engl J Med. 1989 Aug 17;321(7):425-30 [2761576] Pediatrics. 1990 Jan;85(1):1-9 [2404255] Toxicol Appl Pharmacol. 1991 Mar 1;107(3):413-28 [2000632] N Engl J Med. 1994 Jan 20;330(3):188-95 [8264743] JAMA. 1995 Mar 8;273(10):795-8 [7861574] Arch Pediatr Adolesc Med. 1996 Sep;150(9):981-90 [8790132] Dev Med Child Neurol. 1997 Feb;39(2):125-32 [9062428] J Womens Health. 1997 Feb;6(1):49-62 [9065374] Early Hum Dev. 1997 Oct 29;49 Suppl:S29-43 [9363416] Acta Obstet Gynecol Scand. 1998 Jan;77(1):58-62 [9492720] Sci Total Environ. 1998 Apr 23;215(1-2):31-9 [9599454] Chemosphere. 1998 Oct-Nov;37(9-12):1627-43 [9828293] Environ Health Perspect. 1999 Apr;107(4):297-302 [10090709] Int J Epidemiol. 1999 Apr;28(2):179-88 [10342677] Epidemiology. 1999 Jul;10(4):370-5 [10401870] BMJ. 1999 Jul 24;319(7204):245-9 [10417093] Environ Health Perspect. 1999 Jun;107 Suppl 3:409-19 [10346990] Genet Test. 1999;3(3):265-72 [10495925] Environ Health Perspect. 1999 Oct;107(10):843-9 [10504153] Diabetologia. 1999 Dec;42(12):1395-403 [10651256] Brain Inj. 2000 Feb;14(2):181-6 [10695573] Toxicol Ind Health. 2000 Feb;16(2):65-77 [10798624] J Pediatr. 2000 May;136(5):664-72 [10802501] Environ Health Perspect. 2000 May;108(5):387-92 [10811563] Environ Health Perspect. 2000 Jun;108 Suppl 3:451-5 [10852844] Schizophr Bull. 2000;26(2):297-308 [10885632] JAMA. 2000 Oct 11;284(14):1843-9 [11025839] JAMA. 2001 Feb 7;285(5):540-4 [11176855] Urology. 2001 Jan;57(1):151-3 [11164162] Early Hum Dev. 2001 Mar;61(2):85-95 [11223271] Paediatr Perinat Epidemiol. 2001 Jan;15(1):74-87 [11237119] Toxicol Sci. 2001 May;61(1):76-82 [11294977] J Expo Anal Environ Epidemiol. 2001 Sep-Oct;11(5):407-13 [11687914] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduced hepatic tumor incidence in cyclin G1-deficient mice. AN - 73146043; 12668979 AB - Cyclin G1 is a transcriptional target of the tumor suppressor p53, and its expression is increased after DNA damage. Recent data show that cyclin G1 can regulate the levels of p53 by a mechanism that involves dephosphorylation of Mdm2 by protein phosphatase 2A. To understand the biologic role of cyclin G1, we have generated cyclin G1-deficient mice. In agreement with previous results, we showed that these mice develop normally, and that proliferation and induction of cellular senescence in cyclin G1-deficient mouse embryo fibroblasts are indistinguishable from wild-type fibroblasts. However, we found that the p53 levels in the cyclin G1-deficient mice are 2-fold higher that in wild-type mice. Moreover, we showed that treatment of mice with the alkylating agent 1,4-bis[N,N'-di(ethylene)-phosphamide]piperazine (Dipin), followed by partial hepatectomy, decreased G1-S transition in cyclin G1-null hepatocytes as compared with wild type. Finally, we found a significant decrease in tumor incidence, mass, and malignancy in both male and female cyclin G1-null mice after treatment with the potent hepatocarcinogen N-diethylnitrosamine. Taken with recent published data, our results suggest that cyclin G1, together with Mdm2, constitute a part of a negative feedback system that attenuates the activity of p53. In conclusion, our data suggest that the decreased tumor susceptibility after loss of cyclin G1 function is caused by the increased tumor suppressor action of p53. JF - Hepatology (Baltimore, Md.) AU - Jensen, Michael Rugaard AU - Factor, Valentina M AU - Fantozzi, Anna AU - Helin, Kristian AU - Huh, Chang-Goo AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 862 EP - 870 VL - 37 IS - 4 SN - 0270-9139, 0270-9139 KW - Alkylating Agents KW - 0 KW - Ccng1 protein, mouse KW - Cyclin G KW - Cyclin G1 KW - Cyclins KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - Diethylnitrosamine KW - 3IQ78TTX1A KW - Index Medicus KW - Animals KW - DNA Damage KW - Fibroblasts -- physiology KW - Phenotype KW - Fibroblasts -- pathology KW - Hepatocytes -- cytology KW - Liver Regeneration -- physiology KW - Male KW - Cell Division KW - Reference Values KW - Homozygote KW - S Phase KW - Mice KW - Tumor Suppressor Protein p53 -- metabolism KW - Mice, Mutant Strains KW - RNA, Messenger -- metabolism KW - Cell Aging KW - Embryo, Mammalian -- cytology KW - Mice, Inbred C57BL KW - Incidence KW - Female KW - Liver Neoplasms -- prevention & control KW - Cyclins -- deficiency KW - Liver Neoplasms -- chemically induced KW - Liver Neoplasms -- epidemiology KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73146043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reduced+hepatic+tumor+incidence+in+cyclin+G1-deficient+mice.&rft.au=Jensen%2C+Michael+Rugaard%3BFactor%2C+Valentina+M%3BFantozzi%2C+Anna%3BHelin%2C+Kristian%3BHuh%2C+Chang-Goo%3BThorgeirsson%2C+Snorri+S&rft.aulast=Jensen&rft.aufirst=Michael&rft.date=2003-04-01&rft.volume=37&rft.issue=4&rft.spage=862&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-23 N1 - Date created - 2003-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct radiation damage is confined to a single polypeptide in rabbit immunoglobulin G. AN - 73133622; 12668485 AB - Frozen rabbit immunoglobulin G was exposed to high-energy electrons. The surviving polypeptide subunits were determined and analyzed by radiation target analysis. Each subunit was independently damaged by radiation whether or not they were bound by disulfide bridges to other subunits, demonstrating that in IgG radiation-deposited energy did not travel across disulfide bonds. JF - Biophysical journal AU - Miller, J H AU - Draper, L R AU - Kempner, E S AD - Laboratory of Physical Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 2781 EP - 2785 VL - 84 IS - 4 SN - 0006-3495, 0006-3495 KW - Immunoglobulin G KW - 0 KW - Peptides KW - Protein Subunits KW - Index Medicus KW - Animals KW - Rabbits KW - Dose-Response Relationship, Radiation KW - Molecular Weight KW - Immunoglobulin G -- chemistry KW - Peptides -- radiation effects KW - Protein Subunits -- radiation effects KW - Protein Structure, Tertiary -- radiation effects KW - Peptides -- chemistry KW - Immunoglobulin G -- radiation effects KW - Protein Subunits -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73133622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Direct+radiation+damage+is+confined+to+a+single+polypeptide+in+rabbit+immunoglobulin+G.&rft.au=Miller%2C+J+H%3BDraper%2C+L+R%3BKempner%2C+E+S&rft.aulast=Miller&rft.aufirst=J&rft.date=2003-04-01&rft.volume=84&rft.issue=4&rft.spage=2781&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 - 2003-12-09 N1 - Date created - 2003-04-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1965 Dec;240(12):4740-5 [5846989] J Immunol. 1967 Jun;98(6):1190-5 [6026745] Biochem J. 1970 Jan;116(2):261-8 [5461107] Biochemistry. 1981 Nov 10;20(23):6589-94 [6458330] J Biol Chem. 1983 Jan 25;258(2):953-9 [6822516] J Biol Chem. 1983 Oct 10;258(19):11997-2001 [6225783] Biochem J. 1963 Aug;88:220-8 [14063859] Proc Natl Acad Sci U S A. 1985 Aug;82(16):5357-9 [3860867] Methods Enzymol. 1985;117:65-94 [4079816] Biochem J. 1990 Apr 15;267(2):431-9 [2334402] J Biol Chem. 1990 Sep 15;265(26):15776-81 [2203786] Bull Math Biol. 1995 Nov;57(6):883-98 [8528160] J Biol Chem. 1984 Apr 25;259(8):4890-5 [6232271] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Measuring containment of viable infectious cell sorting in high-velocity cell sorters. AN - 73131907; 12655656 AB - With the advent of high-speed sorters, aerosols are a considerable safety concern when sorting viable infectious materials. We describe a four-part safety procedure for validating the containment. This procedure includes aerosol containment, physical barriers, environmental controls, and personal protection. The Aerosol Management System (AMS) produces a negative pressure within the sort chamber, where aerosols are forced through a HEPA filter. Physical barriers include the manufacturer's standard plastic shield and panels. The flow cytometer was contained within a BSL-3 laboratory for maximum environmental control, and the operator was protected by a respiratory system. Containment was measured by using highly fluorescent Glo-Germ particles under the same conditions as the cell sort. Escaping aerosols were vacuumed for 10 min onto a glass slide and examined. With the AMS active and the cytometer producing the maximum aerosols possible, Glo-Germ particles remained within the sort chamber. Measurements taken directly outside the door averaged fewer than one particle per slide, and those taken at 2 ft away and on top of the sorter were completely negative. With this monitoring system in place, aerosols can be efficiently measured, thus reducing the risk to the operator while sorting viable infectious cells. Copyright 2003 Wiley-Liss, Inc. JF - Cytometry. Part A : the journal of the International Society for Analytical Cytology AU - Perfetto, Stephen P AU - Ambrozak, David R AU - Koup, Richard A AU - Roederer, Mario AD - Vaccine Research Center, NAID, National Institute of Health, Bethesda, Maryland 20892-3015, USA. sperfetto@nih.gov Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 122 EP - 130 VL - 52 IS - 2 SN - 1552-4922, 1552-4922 KW - Aerosols KW - 0 KW - Hazardous Substances KW - Index Medicus KW - Humans KW - Occupational Health KW - Flow Cytometry -- instrumentation KW - Equipment Contamination -- prevention & control KW - Hazardous Substances -- analysis KW - Flow Cytometry -- methods KW - Containment of Biohazards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73131907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytometry.+Part+A+%3A+the+journal+of+the+International+Society+for+Analytical+Cytology&rft.atitle=Measuring+containment+of+viable+infectious+cell+sorting+in+high-velocity+cell+sorters.&rft.au=Perfetto%2C+Stephen+P%3BAmbrozak%2C+David+R%3BKoup%2C+Richard+A%3BRoederer%2C+Mario&rft.aulast=Perfetto&rft.aufirst=Stephen&rft.date=2003-04-01&rft.volume=52&rft.issue=2&rft.spage=122&rft.isbn=&rft.btitle=&rft.title=Cytometry.+Part+A+%3A+the+journal+of+the+International+Society+for+Analytical+Cytology&rft.issn=15524922&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-29 N1 - Date created - 2003-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recurring cutaneous eruption in a patient with metastatic renal cell carcinoma being treated with high-dose interleukin 2. AN - 73130958; 12664026 JF - Journal of the American Academy of Dermatology AU - O'Reilly, Fiona AU - Feldman, Elizabeth AU - Yang, James AU - Hwu, Patrick AU - Turner, Maria L AD - Dermatology Branch, National Cancer Institute, Bethesda, MD 20892-1908, USA. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 602 EP - 604 VL - 48 IS - 4 SN - 0190-9622, 0190-9622 KW - Antineoplastic Agents KW - 0 KW - Interleukin-2 KW - Recombinant Proteins KW - Index Medicus KW - Humans KW - Skin -- pathology KW - Recombinant Proteins -- adverse effects KW - Middle Aged KW - Biopsy KW - Recurrence KW - Recombinant Proteins -- administration & dosage KW - Male KW - Kidney Neoplasms -- pathology KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Drug Eruptions -- etiology KW - Antineoplastic Agents -- administration & dosage KW - Carcinoma, Renal Cell -- secondary KW - Carcinoma, Renal Cell -- drug therapy KW - Drug Eruptions -- pathology KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73130958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=proceeding&rft.jtitle=Journal+of+the+American+Academy+of+Dermatology&rft.atitle=Recurring+cutaneous+eruption+in+a+patient+with+metastatic+renal+cell+carcinoma+being+treated+with+high-dose+interleukin+2.&rft.au=O%27Reilly%2C+Fiona%3BFeldman%2C+Elizabeth%3BYang%2C+James%3BHwu%2C+Patrick%3BTurner%2C+Maria+L&rft.aulast=O%27Reilly&rft.aufirst=Fiona&rft.date=2003-04-01&rft.volume=48&rft.issue=4&rft.spage=602&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Dermatology&rft.issn=01909622&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-22 N1 - Date created - 2003-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein. AN - 73127724; 12651870 AB - Expression of misfolded protein in cultured cells frequently leads to the formation of juxtanuclear inclusions that have been termed 'aggresomes'. Aggresome formation is an active cellular response that involves trafficking of the offending protein along microtubules, reorganization of intermediate filaments and recruitment of components of the ubiquitin proteasome system. Whether aggresomes are benevolent or noxious is unknown, but they are of particular interest because of the appearance of similar inclusions in protein deposition diseases. Here we present evidence that aggresomes serve a cytoprotective function and are associated with accelerated turnover of mutant proteins. We show that mutant androgen receptor (AR), the protein responsible for X-linked spinobulbar muscular atrophy, forms insoluble aggregates and is toxic to cultured cells. Mutant AR was also found to form aggresomes in a process distinct from aggregation. Molecular and pharmacological interventions were used to disrupt aggresome formation, revealing their cytoprotective function. Aggresome-forming proteins were found to have an accelerated rate of turnover, and this turnover was slowed by inhibition of aggresome formation. Finally, we show that aggresome-forming proteins become membrane-bound and associate with lysosomal structures. Together, these findings suggest that aggresomes are cytoprotective, serving as cytoplasmic recruitment centers to facilitate degradation of toxic proteins. JF - Human molecular genetics AU - Taylor, J Paul AU - Tanaka, Fumiaki AU - Robitschek, Jon AU - Sandoval, C Miguel AU - Taye, Addis AU - Markovic-Plese, Silva AU - Fischbeck, Kenneth H AD - Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Building 10, Room 3B-14, Bethesda, MD 20892-1250, USA. taylorjp@ninds.nih.gov Y1 - 2003/04/01/ PY - 2003 DA - 2003 Apr 01 SP - 749 EP - 757 VL - 12 IS - 7 SN - 0964-6906, 0964-6906 KW - Multienzyme Complexes KW - 0 KW - Peptides KW - Proteins KW - Receptors, Androgen KW - polyglutamine KW - 26700-71-0 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Multienzyme Complexes -- metabolism KW - Autophagy KW - Cell Nucleus -- metabolism KW - Humans KW - Receptors, Androgen -- genetics KW - Blotting, Western KW - Transfection KW - Cysteine Endopeptidases -- metabolism KW - Protein Folding KW - Mutation KW - Cell Line KW - Protein Transport KW - Inclusion Bodies -- metabolism KW - Lysosomes -- ultrastructure KW - Lysosomes -- metabolism KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73127724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aggresomes+protect+cells+by+enhancing+the+degradation+of+toxic+polyglutamine-containing+protein.&rft.au=Taylor%2C+J+Paul%3BTanaka%2C+Fumiaki%3BRobitschek%2C+Jon%3BSandoval%2C+C+Miguel%3BTaye%2C+Addis%3BMarkovic-Plese%2C+Silva%3BFischbeck%2C+Kenneth+H&rft.aulast=Taylor&rft.aufirst=J&rft.date=2003-04-01&rft.volume=12&rft.issue=7&rft.spage=749&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 - 2003-12-11 N1 - Date created - 2003-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Contribution of individual cytochrome P450 isozymes to the O-demethylation of the psychotropic beta-carboline alkaloids harmaline and harmine. AN - 73125469; 12649384 AB - The psychotropic beta-carboline alkaloids, showing high affinity for 5-hydroxytryptamine, dopamine, benzodiazepine, and imidazoline receptors and the stimulation of locus coeruleus neurons, are formed endogenously from tryptophan-derived indolealkylamines through the Pictet-Spengler condensation with aldehydes in both plants and mammals. Cytochromes P450 1A1 (18.5), 1A2 (20), and 2D6 (100) catalyzed the O-demethylation of harmaline, and CYP1A1 (98.5), CYP1A2 (35), CYP2C9 (16), CYP2C19 (30), and CYP2D6 (115) catalyzed that of harmine (relative activities). The dehydrogenation/aromatization of harmaline to harmine was not carried out by aromatase (CYP19), CYP1A2, CYP2C9, CYP2D6, CYP3A4, pooled recombinant cytochromes P450, or human liver microsomes (HLMs). Kinetic parameters were calculated for the O-demethylations mediated by each isozyme and by pooled HLMs. K(cat) (min(-1)) and K(m) Awake M) values for harmaline were: CYP1A1, 10.8 and 11.8; CYP1A2, 12.3 and 13.3; CYP2C9, 5.3 and 175; CYP2C19, 10.3 and 160; and CYP2D6, 39.9 and 1.4. Values for harmine were: CYP1A1, 45.2 and 52.2; CYP1A2, 9.2 and 14.7; CYP2C9, 11.9 and 117; CYP2C19, 21.4 and 121; and CYP2D6, 29.7 and 7.4. Inhibition studies using monoclonal antibodies confirmed that CYP1A2 and CYP2D6 were the major isozymes contributing to both harmaline (20% and 50%, respectively) and harmine (20% and 30%) O-demethylations in pooled HLMs. The turnover numbers for CYP2D6 are among the highest ever reported for a CYP2D6 substrate. Finally, CYP2D6-transgenic mice were found to have increased harmaline and harmine O-demethylase activities as compared with wild-type mice. These findings suggest a role for polymorphic CYP2D6 in the pharmacology and toxicology of harmine and harmaline. JF - The Journal of pharmacology and experimental therapeutics AU - Yu, Ai-Ming AU - Idle, Jeffrey R AU - Krausz, Kristopher W AU - Küpfer, Adrian AU - Gonzalez, Frank J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 315 EP - 322 VL - 305 IS - 1 SN - 0022-3565, 0022-3565 KW - DNA, Complementary KW - 0 KW - Isoenzymes KW - Psychotropic Drugs KW - Harmine KW - 4FHH5G48T7 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Harmaline KW - CN58I4TOET KW - Index Medicus KW - Mass Spectrometry KW - Animals KW - DNA, Complementary -- genetics KW - Microsomes, Liver -- metabolism KW - Kinetics KW - Humans KW - In Vitro Techniques KW - Mice KW - Mice, Transgenic KW - Methylation KW - Male KW - Chromatography, High Pressure Liquid KW - Harmine -- metabolism KW - Psychotropic Drugs -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Harmaline -- metabolism KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73125469?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Contribution+of+individual+cytochrome+P450+isozymes+to+the+O-demethylation+of+the+psychotropic+beta-carboline+alkaloids+harmaline+and+harmine.&rft.au=Yu%2C+Ai-Ming%3BIdle%2C+Jeffrey+R%3BKrausz%2C+Kristopher+W%3BK%C3%BCpfer%2C+Adrian%3BGonzalez%2C+Frank+J&rft.aulast=Yu&rft.aufirst=Ai-Ming&rft.date=2003-04-01&rft.volume=305&rft.issue=1&rft.spage=315&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 - 2003-04-22 N1 - Date created - 2003-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Male mice deficient in microsomal epoxide hydrolase are not susceptible to benzene-induced toxicity. AN - 73124575; 12655032 AB - Enzymes involved in benzene metabolism are likely genetic determinants of benzene-induced toxicity. Polymorphisms in human microsomal epoxide hydrolase (mEH) are associated with an increased risk of developing leukemia, specifically those associated with benzene. This study was designed to investigate the importance of mEH in benzene-induced toxicity. Male and female mEH-deficient (mEH-/-) mice and background mice (129/Sv) were exposed to inhaled benzene (0, 10, 50, or 100 ppm) 5 days/week, 6 h/day, for a two-week duration. Total white blood cell counts and bone marrow cell counts were used to assess hematotoxicity and myelotoxicity. Micronucleated peripheral blood cells were counted to assess genotoxicity, and the p21 mRNA level in bone marrow cells was used as a determinant of the p53-regulated DNA damage response. Male mEH-/- mice did not have any significant hematotoxicity or myelotoxicity at the highest benzene exposure compared to the male 129/Sv mice. Significant hematotoxicity or myelotoxicity did not occur in the female mEH-/- or 129/Sv mice. Male mEH-/- mice were also unresponsive to benzene-induced genotoxicity compared to a significant induction in the male 129/Sv mice. The female mEH-/- and 129/Sv mice were virtually unresponsive to benzene-induced genotoxicity. While p21 mRNA expression was highly induced in male 129/Sv mice after exposure to 100-ppm benzene, no significant alteration was observed in male mEH-/- mice. Likewise, p21 mRNA expression in female mEH-/- mice was not significantly induced upon benzene exposure whereas a significant induction was observed in female 129/Sv mice. Thus mEH appears to be critical in benzene-induced toxicity in male, but not female, mice. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Bauer, Alison K AU - Faiola, Brenda AU - Abernethy, Diane J AU - Marchan, Rosemarie AU - Pluta, Linda J AU - Wong, Victoria A AU - Gonzalez, Frank J AU - Butterworth, Byron E AU - Borghoff, Susan J AU - Everitt, Jeffrey I AU - Recio, Leslie AD - CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709, USA. bauer1@niehs.nih.gov Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 201 EP - 209 VL - 72 IS - 2 SN - 1096-6080, 1096-6080 KW - Cdkn1a protein, mouse KW - 0 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - RNA, Messenger KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - Benzene KW - J64922108F KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Animals KW - Sex Factors KW - Dose-Response Relationship, Drug KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Knockout KW - Leukocytes -- drug effects KW - Mice, Inbred Strains KW - Micronucleus Tests KW - Inactivation, Metabolic KW - RNA, Messenger -- metabolism KW - Leukocytes -- pathology KW - Cyclins -- metabolism KW - Administration, Inhalation KW - Cyclins -- genetics KW - Female KW - Male KW - Bone Marrow Cells -- drug effects KW - Epoxide Hydrolases -- metabolism KW - Benzene -- pharmacokinetics KW - Benzene -- toxicity KW - Hematologic Diseases -- metabolism KW - Epoxide Hydrolases -- deficiency KW - Benzene -- administration & dosage KW - Epoxide Hydrolases -- genetics KW - Bone Marrow Cells -- metabolism KW - Hematologic Diseases -- chemically induced KW - Bone Marrow Cells -- pathology KW - Hematologic Diseases -- pathology KW - Genetic Predisposition to Disease UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73124575?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Male+mice+deficient+in+microsomal+epoxide+hydrolase+are+not+susceptible+to+benzene-induced+toxicity.&rft.au=Bauer%2C+Alison+K%3BFaiola%2C+Brenda%3BAbernethy%2C+Diane+J%3BMarchan%2C+Rosemarie%3BPluta%2C+Linda+J%3BWong%2C+Victoria+A%3BGonzalez%2C+Frank+J%3BButterworth%2C+Byron+E%3BBorghoff%2C+Susan+J%3BEveritt%2C+Jeffrey+I%3BRecio%2C+Leslie&rft.aulast=Bauer&rft.aufirst=Alison&rft.date=2003-04-01&rft.volume=72&rft.issue=2&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-26 N1 - Date created - 2003-03-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dextromethorphan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation. AN - 73123975; 12649371 AB - Inflammation in the brain has increasingly been recognized to play an important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Inflammation-mediated neurodegeneration involves activation of the brain's resident immune cells, the microglia, which produce proinflammatory and neurotoxic factors, including cytokines, reactive oxygen intermediates, nitric oxide, and eicosanoids that impact on neurons to induce neurodegeneration. Hence, identification of compounds that prevent microglial activation may be highly desirable in the search for therapeutic agents for inflammation-mediated neurodegenerative diseases. In this study, we report that dextromethorphan (DM), an ingredient widely used in antitussive remedies, reduced the inflammation-mediated degeneration of dopaminergic neurons through inhibition of microglial activation. Pretreatment (30 min) of rat mesencephalic neuron-glia cultures with DM (1-10 micro M) reduced, in a dose-dependent manner, the microglia-mediated degeneration of dopaminergic neurons induced by lipopolysaccharide (LPS, 10 ng/ml). Significant neuroprotection by DM was also evident when DM was applied to cultures up to 60 min after the addition of LPS. The neuroprotective effect of DM was attributed to inhibition of LPS-stimulated microglial activation because DM significantly inhibited the LPS-induced production of tumor necrosis factor-alpha, nitric oxide, and superoxide free radicals. This conclusion was further supported by the finding that DM failed to prevent 1-methyl-4-phenylpyridinium- or beta-amyloid peptide (1-42)-induced dopaminergic neurotoxicity in neuron-enriched cultures. In addition, because LPS did not produce any significant increase in the release of excitatory amino acids from neuron-glia cultures and N-methyl-D-aspartate antagonist dizocilpine maleate failed to afford significant neuroprotection, it is unlikely that the neuroprotective effect of DM is mediated through N-methyl-D-aspartate receptors. These results suggest that DM may be a promising therapeutic agent for the treatment of Parkinson's disease. JF - The Journal of pharmacology and experimental therapeutics AU - Liu, Yuxin AU - Qin, Liya AU - Li, Guorong AU - Zhang, Wei AU - An, Lijia AU - Liu, Bin AU - Hong, Jau-Shyong AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 212 EP - 218 VL - 305 IS - 1 SN - 0022-3565, 0022-3565 KW - Amyloid beta-Peptides KW - 0 KW - Lipopolysaccharides KW - Neuroprotective Agents KW - Receptors, Dopamine KW - Superoxides KW - 11062-77-4 KW - Xanthine KW - 1AVZ07U9S7 KW - Dextromethorphan KW - 7355X3ROTS KW - Xanthine Oxidase KW - EC 1.17.3.2 KW - 1-Methyl-4-phenylpyridinium KW - R865A5OY8J KW - Index Medicus KW - Xanthine Oxidase -- metabolism KW - Animals KW - Drug Interactions KW - Inflammation -- physiopathology KW - Xanthine -- metabolism KW - Rats KW - Rats, Inbred F344 KW - Superoxides -- metabolism KW - Cells, Cultured KW - Receptors, Dopamine -- metabolism KW - Microglia -- physiology KW - Neurons -- drug effects KW - Dextromethorphan -- pharmacology KW - Neurons -- physiology KW - Nerve Degeneration -- chemically induced KW - Nerve Degeneration -- prevention & control KW - Dextromethorphan -- therapeutic use KW - Neuroprotective Agents -- therapeutic use KW - Microglia -- drug effects KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73123975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dextromethorphan+protects+dopaminergic+neurons+against+inflammation-mediated+degeneration+through+inhibition+of+microglial+activation.&rft.au=Liu%2C+Yuxin%3BQin%2C+Liya%3BLi%2C+Guorong%3BZhang%2C+Wei%3BAn%2C+Lijia%3BLiu%2C+Bin%3BHong%2C+Jau-Shyong&rft.aulast=Liu&rft.aufirst=Yuxin&rft.date=2003-04-01&rft.volume=305&rft.issue=1&rft.spage=212&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 - 2003-04-22 N1 - Date created - 2003-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of trespin expression by modulators of cell growth, differentiation, and apoptosis in prostatic epithelial cells. AN - 73121474; 12651162 AB - We recently identified a novel rat ov-serpin, Trespin, which inhibits the trypsin-like serine proteinase plasmin and is expressed in several tissues, including prostate. In this report Trespin expression was studied in prostatic cell lines, NRP-152, NRP-154, and DP-153, derived from the Lobund-Wistar rat. Northern blots revealed Trespin mRNA is expressed in NRP-152 and DP-153 basal epithelial cell lines but not in the luminal line, NRP-154. Similarly, Trespin levels drop >30-fold following transdifferentiation of NRP-152 cells toward a luminal variant, further suggesting Trespin expression is specific for basal prostatic epithelial cells. Trespin expression in NRP-152 cells is up-regulated by dexamethasone (Dex) and insulin-like growth factor-I (IGF-I), each of which stimulate growth and prevent differentiation and apoptosis. However, Dex (alone) facilitates loss of Trespin by TGF-beta, yet enhances the ability of LR(3)-IGF-I to reverse such loss, similar to the pattern of apoptosis induced by TGF-beta. Likewise, several apoptosis inducers markedly decrease Trespin mRNA levels. HEK293 cells stably overexpressing Trespin display increased cell proliferation and partial resistance to growth inhibition and phosphorylation of c-Jun induced by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). Together these data strongly suggest that Trespin has critical functions tied to the regulation of growth, differentiation, and apoptosis of prostatic epithelial cells. JF - Experimental cell research AU - Stewart, LaMonica V AU - Song, Kyung AU - Hsing, Andrew Y AU - Danielpour, David AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2003/04/01/ PY - 2003 DA - 2003 Apr 01 SP - 303 EP - 315 VL - 284 IS - 2 SN - 0014-4827, 0014-4827 KW - Phorbol Esters KW - 0 KW - Proto-Oncogene Proteins c-jun KW - RNA, Messenger KW - Serpins KW - TGFB1 protein, human KW - Tgfb1 protein, rat KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - trespin protein, rat KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Dexamethasone -- pharmacology KW - Humans KW - RNA, Messenger -- drug effects KW - Proto-Oncogene Proteins c-jun -- drug effects KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Insulin-Like Growth Factor I -- pharmacology KW - Gene Expression Regulation -- genetics KW - Up-Regulation -- physiology KW - Rats KW - Phorbol Esters -- pharmacology KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Up-Regulation -- drug effects KW - Gene Expression Regulation -- drug effects KW - Male KW - Epithelial Cells -- metabolism KW - Prostate -- drug effects KW - Prostate -- growth & development KW - Epithelial Cells -- drug effects KW - Cell Differentiation -- physiology KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Prostate -- metabolism KW - Cell Division -- physiology KW - Cell Division -- drug effects KW - Cell Differentiation -- drug effects KW - Serpins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73121474?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cell+research&rft.atitle=Regulation+of+trespin+expression+by+modulators+of+cell+growth%2C+differentiation%2C+and+apoptosis+in+prostatic+epithelial+cells.&rft.au=Stewart%2C+LaMonica+V%3BSong%2C+Kyung%3BHsing%2C+Andrew+Y%3BDanielpour%2C+David&rft.aulast=Stewart&rft.aufirst=LaMonica&rft.date=2003-04-01&rft.volume=284&rft.issue=2&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-16 N1 - Date created - 2003-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - PKA/PrKX activity is a modulator of AAV/adenovirus interaction. AN - 73120794; 12660177 AB - Interference between viruses occurs when infection by one virus results in the inhibition of replication of another virus. Adeno-associated virus (AAV2) is a human parvovirus with the unique characteristics of a dependence upon a helper virus for a productive infection and the ability to interfere with the replication of the helper virus. Previously, we demonstrated that AAV2 Rep78 and Rep52 interact and inhibit cAMP-dependent protein kinase A (PKA) and its novel homolog PrKX. We hypothesized that modulation of PKA activity by AAV2 may be responsible for inhibition of helper virus replication. In this study we demonstrate that adenovirus replication is sensitive to PKA activity and that AAV2 Rep78/Rep52 proteins contain an inhibitory domain similar to that of the heat-stable PKA inhibitor. This domain, while not directly necessary for AAV2 replication and packaging, is necessary to preserve AAV2 replication fitness during an Ad co-infection. Furthermore, a mutant AAV2 virus lacking this region fails to inhibit adenovirus replication. Thus, inhibition of PKA activity by AAV2 constitutes a novel form of viral interference. JF - The EMBO journal AU - Di Pasquale, Giovanni AU - Chiorini, John A AD - Gene Therapy and Therapeutics Branch, NIDCR, NIH 10/1N113, 10 Center Drive MSC 1190, Bethesda, MD 20892-1190, USA. Y1 - 2003/04/01/ PY - 2003 DA - 2003 Apr 01 SP - 1716 EP - 1724 VL - 22 IS - 7 SN - 0261-4189, 0261-4189 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Viral Proteins KW - rep proteins, Adeno-associated virus 2 KW - 137750-19-7 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Virus Replication KW - HeLa Cells KW - Humans KW - Amino Acid Sequence KW - Protein Binding KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Molecular Sequence Data KW - Viral Proteins -- metabolism KW - Sequence Homology, Amino Acid KW - Amino Acid Substitution KW - DNA-Binding Proteins -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Dependovirus -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73120794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=PKA%2FPrKX+activity+is+a+modulator+of+AAV%2Fadenovirus+interaction.&rft.au=Di+Pasquale%2C+Giovanni%3BChiorini%2C+John+A&rft.aulast=Di+Pasquale&rft.aufirst=Giovanni&rft.date=2003-04-01&rft.volume=22&rft.issue=7&rft.spage=1716&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-14 N1 - Date created - 2003-03-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1995 Nov;69(11):6787-96 [7474090] J Virol. 1995 Sep;69(9):5485-96 [7636994] J Virol. 1996 Feb;70(2):1050-60 [8551563] Nature. 1996 Apr 18;380(6575):642-6 [8602268] J Virol. 1996 Mar;70(3):1784-91 [8627701] J Virol. 1997 Jun;71(6):4300-9 [9151818] J Gen Virol. 1997 Jun;78 ( Pt 6):1441-52 [9191942] J Immunol. 1998 Jul 15;161(2):610-6 [9670934] J Virol. 1998 Oct;72(10):7916-25 [9733829] Mol Cell Biol. 1998 Oct;18(10):5921-9 [9742109] J Clin Virol. 1999 Jun;13(1-2):61-9 [10405893] Proc R Soc Lond B Biol Sci. 1957 Sep 12;147(927):258-67 [13465720] Science. 1965 Aug 13;149(3685):754-6 [14325163] J Virol. 2000 Apr;74(8):3494-504 [10729123] EMBO J. 2000 Aug 15;19(16):4351-61 [10944118] EMBO J. 2001 Mar 15;20(6):1310-9 [11250897] J Virol. 2001 Aug;75(15):6884-93 [11435568] Oncogene. 2001 Jun 28;20(29):3824-34 [11439346] N Engl J Med. 2001 Sep 6;345(10):707-14 [11547739] Annu Rev Microbiol. 2001;55:255-81 [11544356] J Virol. 2002 Feb;76(3):1033-42 [11773379] Virology. 2001 Dec 20;291(2):260-71 [11878895] Virology. 1967 May;32(1):52-9 [4290509] J Virol. 1967 Feb;1(1):171-80 [4990036] J Gen Virol. 1970 Aug;8(2):105-11 [5477329] J Biol Chem. 1971 Apr 10;246(7):1977-85 [4324557] Virology. 1979 Jan 30;92(2):449-62 [218354] J Virol. 1981 Oct;40(1):241-7 [6270377] Gene. 1983 Jul;23(1):65-73 [6352411] Virology. 1984 Apr 15;134(1):64-71 [6200995] Virology. 1985 Nov;147(1):217-22 [2998066] J Gen Virol. 1986 Jan;67 ( Pt 1):181-5 [3003233] Virology. 1986 Jul 15;152(1):110-7 [3012864] Proc Natl Acad Sci U S A. 1987 Dec;84(23):8355-9 [2960975] Virology. 1988 May;164(1):64-74 [2834875] Arch Virol. 1988;103(1-2):133-7 [2850777] J Virol. 1989 Jul;63(7):3057-64 [2542614] Curr Top Microbiol Immunol. 1989;144:191-5 [2676360] Proc Natl Acad Sci U S A. 1990 Mar;87(6):2211-5 [2156265] Virology. 1990 Dec;179(2):632-9 [2173256] J Virol. 1991 Jan;65(1):396-404 [1845899] Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):48-52 [1846042] Science. 1991 Jul 26;253(5018):407-14 [1862342] Virology. 1992 Jul;189(1):329-33 [1318608] AIDS Res Hum Retroviruses. 1992 Jul;8(7):1255-61 [1381600] J Gen Virol. 1992 Nov;73 ( Pt 11):2977-81 [1331299] Endocrinology. 1993 Feb;132(2):770-80 [8381074] Mutat Res. 1994 Mar 1;305(2):303-13 [7510040] Cancer Res. 1994 Apr 15;54(8):2278-81 [8174138] Biochem Biophys Res Commun. 1995 Oct 24;215(3):928-36 [7488063] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34. AN - 73111913; 12648211 AB - It is widely believed that epithelial stem cells reside in the hair follicle bulge region. We investigated the hematopoietic stem and progenitor cell marker, CD34, as a potential marker of hair follicle bulge keratinocytes. Using a CD34-specific antibody, we identified intense membrane staining on keratinocytes in the bulge region of the mouse hair follicle. CD34 expression colocalized with both slowly cycling (label retaining) cells and keratin 15 expression. Live CD34+ keratinocytes were positively selected using antibodies to CD34 and alpha6 integrin in combination with fluorescent activated cell sorting. Sorted cells were analyzed for DNA content, and a staining profile was generated to confirm these cells as keratinocytes. CD34+ keratinocytes were predominantly in Go/G1, in contrast to CD34- cells, which had well defined G2/M and S phases. In addition, CD34+ keratinocytes were found to express alpha6 integrin more intensely than CD34- cells (p<0.05), identifying this population as an alpha6 integrin bright subset. When seeded at clonal density, CD34+ keratinocytes formed larger colonies than CD34- cells (p<0.05), indicating a higher proliferative potential. All flow-sorted cells were positive for keratin 14 expression, and negative for keratin 1, loricrin, vimentin, and CD31. The majority of CD34+ cells (98%) were positive for keratin 6, establishing this population as basal keratinocytes of follicular origin. CD34 message was detected by reverse transcription polymerase chain reaction predominantly in the CD34+ keratinocytes, confirming specificity of the antibody. This work is the first to demonstrate that CD34 is a specific marker of bulge cell keratinocytes in the cutaneous epithelium. Furthermore, the use of this marker facilitates isolation of live epithelial cells with stem and progenitor cell characteristics, potentially providing a tool for the study of carcinogen target cells, gene therapy, and tissue engineering applications. JF - The Journal of investigative dermatology AU - Trempus, Carol S AU - Morris, Rebecca J AU - Bortner, Carl D AU - Cotsarelis, George AU - Faircloth, Randall S AU - Reece, Jeffrey M AU - Tennant, Raymond W AD - Cancer Biology Group, National Center for Toxicogenomics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. trempus@NIEHS.NIH.gov Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 501 EP - 511 VL - 120 IS - 4 SN - 0022-202X, 0022-202X KW - Antigens, CD34 KW - 0 KW - Antigens, Surface KW - Integrin alpha6 KW - Index Medicus KW - Animals KW - Stem Cells -- chemistry KW - Mice KW - Mice, Transgenic KW - Mice, Inbred BALB C KW - Antigens, Surface -- immunology KW - Antibody Specificity KW - Integrin alpha6 -- analysis KW - Stem Cells -- cytology KW - Mice, Inbred C57BL KW - Integrin alpha6 -- immunology KW - Flow Cytometry KW - Antigens, Surface -- analysis KW - Female KW - Cell Division KW - Keratinocytes -- chemistry KW - Antigens, CD34 -- immunology KW - Hair Follicle -- cytology KW - Keratinocytes -- cytology KW - Antigens, CD34 -- analysis KW - Cell Separation -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73111913?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigative+dermatology&rft.atitle=Enrichment+for+living+murine+keratinocytes+from+the+hair+follicle+bulge+with+the+cell+surface+marker+CD34.&rft.au=Trempus%2C+Carol+S%3BMorris%2C+Rebecca+J%3BBortner%2C+Carl+D%3BCotsarelis%2C+George%3BFaircloth%2C+Randall+S%3BReece%2C+Jeffrey+M%3BTennant%2C+Raymond+W&rft.aulast=Trempus&rft.aufirst=Carol&rft.date=2003-04-01&rft.volume=120&rft.issue=4&rft.spage=501&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+investigative+dermatology&rft.issn=0022202X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-02 N1 - Date created - 2003-03-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Invest Dermatol. 2003 Nov;121(5):1220; author reply 1220-1 [14708630] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidant signals and oxidative stress. AN - 73109900; 12648682 AB - Although oxidants clearly possess the capacity to behave in a random and destructive fashion, growing evidence suggests that in many instances the production of reactive oxygen species is tightly regulated and their downstream targets exquisitely specific. This past year, several notable advances have been made in defining the specific redox-dependent targets of intracellular oxidants, as well as the myriad pathways that appear to employ oxidants as effector molecules. These new studies have significantly altered our understanding of how reactive oxygen species participate in diverse processes from tumourigenesis to ageing. JF - Current opinion in cell biology AU - Finkel, Toren AD - Cardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive, , Bethesda, MD 20892-1622, USA. finkelt@nih.gov Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 247 EP - 254 VL - 15 IS - 2 SN - 0955-0674, 0955-0674 KW - Antioxidants KW - 0 KW - Oxidants KW - Reactive Oxygen Species KW - Oxidoreductases KW - EC 1.- KW - Index Medicus KW - Oxidation-Reduction KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Antioxidants -- metabolism KW - Oxidoreductases -- metabolism KW - Humans KW - Eukaryotic Cells -- metabolism KW - Signal Transduction -- physiology KW - Oxidative Stress -- physiology KW - Oxidants -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73109900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+cell+biology&rft.atitle=Oxidant+signals+and+oxidative+stress.&rft.au=Finkel%2C+Toren&rft.aulast=Finkel&rft.aufirst=Toren&rft.date=2003-04-01&rft.volume=15&rft.issue=2&rft.spage=247&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+cell+biology&rft.issn=09550674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-02 N1 - Date created - 2003-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence and correlates of areca nut use among psychiatric patients in India. AN - 73102737; 12633917 AB - To estimate the prevalence and identify the correlates of areca nut use among men and women being treated for a major psychiatric disorder in India. Inpatients (N=988) admitted to the adult psychiatry department of the National Institute of Mental Health and Neuro Sciences in India were interviewed regarding their use of the areca nut, tobacco, alcohol, and other drugs. Medical records were reviewed to obtain psychiatric diagnosis and history. About 24% of the sample reported recent areca nut use, and 10% reported severe use suggesting dependence. Common reasons for use include to improve mood (31% of users), socialization (31%), digestion (22%), or performance (7%) and to decrease aches and pains (6%). Predictors of current areca nut use included less education, diagnosis of bipolar disorder, and current tobacco use. Predictors of severe use were older age, female gender, less education, and current tobacco use. Areca nut use occurs commonly among Indian psychiatric patients, and deserves further investigation. JF - Drug and alcohol dependence AU - Chandra, Prabha S AU - Carey, Michael P AU - Carey, Kate B AU - Jairam, K R AD - Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore 560029, India. prabhachandra@rediffmail.com Y1 - 2003/04/01/ PY - 2003 DA - 2003 Apr 01 SP - 311 EP - 316 VL - 69 IS - 3 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Psychiatric Department, Hospital -- statistics & numerical data KW - India -- epidemiology KW - Cross-Sectional Studies KW - Bipolar Disorder -- epidemiology KW - Patient Admission KW - Motivation KW - Humans KW - Adult KW - Bipolar Disorder -- psychology KW - Male KW - Female KW - Comorbidity KW - Areca KW - Mental Disorders -- epidemiology KW - Nuts KW - Mental Disorders -- psychology KW - Developing Countries KW - Substance-Related Disorders -- psychology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73102737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Prevalence+and+correlates+of+areca+nut+use+among+psychiatric+patients+in+India.&rft.au=Chandra%2C+Prabha+S%3BCarey%2C+Michael+P%3BCarey%2C+Kate+B%3BJairam%2C+K+R&rft.aulast=Chandra&rft.aufirst=Prabha&rft.date=2003-04-01&rft.volume=69&rft.issue=3&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-29 N1 - Date created - 2003-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection. AN - 73100022; 12633912 AB - With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients. JF - Drug and alcohol dependence AU - Umbricht, Annie AU - Hoover, Donald R AU - Tucker, Marvin J AU - Leslie, Jo M AU - Chaisson, Richard E AU - Preston, Kenzie L AD - National Institute on Drug Abuse Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003/04/01/ PY - 2003 DA - 2003 Apr 01 SP - 263 EP - 272 VL - 69 IS - 3 SN - 0376-8716, 0376-8716 KW - Adrenergic alpha-Agonists KW - 0 KW - Narcotics KW - Receptors, Opioid KW - Buprenorphine KW - 40D3SCR4GZ KW - Clonidine KW - MN3L5RMN02 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Receptors, Opioid -- agonists KW - Administration, Oral KW - Drug Administration Schedule KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Injections, Intramuscular KW - Adult KW - Treatment Outcome KW - Pain Measurement KW - Middle Aged KW - Male KW - Female KW - Methadone -- therapeutic use KW - Buprenorphine -- therapeutic use KW - Hospitalization KW - HIV Infections -- transmission KW - Substance Withdrawal Syndrome -- diagnosis KW - Substance Abuse, Intravenous -- rehabilitation KW - Narcotics -- therapeutic use KW - Heroin Dependence -- rehabilitation KW - Clonidine -- therapeutic use KW - Adrenergic alpha-Agonists -- therapeutic use KW - HIV Infections -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73100022?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Opioid+detoxification+with+buprenorphine%2C+clonidine%2C+or+methadone+in+hospitalized+heroin-dependent+patients+with+HIV+infection.&rft.au=Umbricht%2C+Annie%3BHoover%2C+Donald+R%3BTucker%2C+Marvin+J%3BLeslie%2C+Jo+M%3BChaisson%2C+Richard+E%3BPreston%2C+Kenzie+L&rft.aulast=Umbricht&rft.aufirst=Annie&rft.date=2003-04-01&rft.volume=69&rft.issue=3&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-29 N1 - Date created - 2003-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Caveolin-induced activation of the phosphatidylinositol 3-kinase/Akt pathway increases arsenite cytotoxicity. AN - 73098249; 12640124 AB - The inhibitory effect of caveolin on the cellular response to growth factor stimulation is well established. Given the significant overlap in signaling pathways involved in regulating cell proliferation and stress responsiveness, we hypothesized that caveolin would also affect a cell's ability to respond to environmental stress. Here we investigated the ability of caveolin-1 to modulate the cellular response to sodium arsenite and thereby alter survival of the human cell lines 293 and HeLa. Cells stably transfected with caveolin-1 were found to be much more sensitive to the toxic effects of sodium arsenite than either untransfected parental cells or parental cells transfected with an empty vector. Unexpectedly, the caveolin-overexpressing cells also exhibited a significant activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which additional studies suggested was likely due to decreased neutral sphingomyelinase activity and ceramide synthesis. In contrast to its extensively documented antiapoptotic influence, the elevated activity of Akt appears to be important in sensitizing caveolin-expressing cells to arsenite-induced toxicity, as both pretreatment of cells with the PI3K inhibitor wortmannin and overexpression of a dominant-negative Akt mutant markedly improved the survival of arsenite-treated cells. This death-promoting influence of the PI3K/Akt pathway in caveolin-overexpressing cells appeared not to be unique to sodium arsenite, as wortmannin pretreatment also resulted in increased survival in the presence of H(2)O(2). In summary, our results indicate that caveolin-induced upregulation of the PI3K/Akt signaling pathway, which appears to be a death signal in the presence of arsenite and H(2)O(2), sensitizes cells to environmental stress. JF - Molecular and cellular biology AU - Shack, Sonsoles AU - Wang, Xian-Tao AU - Kokkonen, Gertrude C AU - Gorospe, Myriam AU - Longo, Dan L AU - Holbrook, Nikki J AD - Laboratory of Cellular and Molecular Biology, National Institute on Aging-IRP, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 2407 EP - 2414 VL - 23 IS - 7 SN - 0270-7306, 0270-7306 KW - Androstadienes KW - 0 KW - Arsenites KW - CAV1 protein, human KW - Caveolin 1 KW - Caveolins KW - Ceramides KW - Enzyme Inhibitors KW - Oxidants KW - Proto-Oncogene Proteins KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - arsenite KW - N5509X556J KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Fibroblasts -- drug effects KW - Oxidants -- pharmacology KW - Cell Survival -- genetics KW - HeLa Cells KW - Humans KW - Androstadienes -- pharmacology KW - Ceramides -- metabolism KW - Fibroblasts -- cytology KW - Fibroblasts -- metabolism KW - Enzyme Activation -- genetics KW - Blotting, Western KW - Phosphorylation KW - Genes, Dominant KW - Cell Survival -- drug effects KW - Transfection KW - Enzyme Activation -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Cell Line KW - Signal Transduction -- physiology KW - Caveolins -- genetics KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Caveolins -- metabolism KW - Signal Transduction -- drug effects KW - Arsenites -- toxicity KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73098249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Caveolin-induced+activation+of+the+phosphatidylinositol+3-kinase%2FAkt+pathway+increases+arsenite+cytotoxicity.&rft.au=Shack%2C+Sonsoles%3BWang%2C+Xian-Tao%3BKokkonen%2C+Gertrude+C%3BGorospe%2C+Myriam%3BLongo%2C+Dan+L%3BHolbrook%2C+Nikki+J&rft.aulast=Shack&rft.aufirst=Sonsoles&rft.date=2003-04-01&rft.volume=23&rft.issue=7&rft.spage=2407&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 - 2003-04-04 N1 - Date created - 2003-03-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Free Radic Biol Med. 1996;21(6):783-90 [8902524] J Immunol. 1996 Oct 15;157(8):3381-90 [8871635] J Biol Chem. 1997 Mar 14;272(11):7211-22 [9054417] Genes Dev. 1998 Jul 1;12(13):1941-6 [9649498] FEBS Lett. 1998 May 29;428(3):205-11 [9654135] Biochem J. 1998 Jul 15;333 ( Pt 2):291-300 [9657968] Mol Cell Biol. 1998 Sep;18(9):5178-88 [9710602] J Investig Dermatol Symp Proc. 1998 Aug;3(1):23-7 [9732053] Annu Rev Biochem. 1998;67:199-225 [9759488] Am J Physiol. 1998 Nov;275(5 Pt 1):L843-51 [9815100] EMBO J. 1998 Nov 16;17(22):6633-48 [9822607] J Cell Biol. 1999 Aug 23;146(4):697-702 [10459005] Mol Cell Biol. 1999 Nov;19(11):7289-304 [10523618] J Biophys Biochem Cytol. 1955 Sep 25;1(5):445-58 [13263332] J Biol Chem. 1998 Mar 6;273(10):5419-22 [9488658] Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12866-9 [10536014] Genes Dev. 1999 Nov 15;13(22):2905-27 [10579998] Blood. 2000 Feb 1;95(3):1078-85 [10648425] Mol Cell Biol. 2000 Mar;20(5):1507-14 [10669728] J Biol Chem. 2000 Feb 25;275(8):5710-7 [10681556] J Biol Chem. 2000 May 12;275(19):14624-31 [10799549] J Biol Chem. 2000 Jul 7;275(27):20847-52 [10781609] J Biol Chem. 2000 Dec 15;275(50):39435-43 [10993883] J Cell Physiol. 2001 Mar;186(3):329-37 [11169971] Nature. 2001 Mar 1;410(6824):37-40 [11242034] Toxicology. 2001 Mar 7;160(1-3):227-36 [11246143] Am J Physiol Cell Physiol. 2001 Apr;280(4):C823-35 [11245599] Biochem J. 2001 May 1;355(Pt 3):859-68 [11311151] Biochem Soc Trans. 2001 Aug;29(Pt 4):494-9 [11498016] Brain Res Mol Brain Res. 2001 Sep 10;93(1):18-26 [11532334] FASEB J. 2002 Jan;16(1):114-6 [11709495] J Cell Biol. 1968 Jun;37(3):633-49 [11905197] Science. 2002 Mar 29;295(5564):2450-2 [11884717] J Cell Physiol. 2002 Jul;192(1):1-15 [12115731] Biochem Biophys Res Commun. 2002 Sep 27;297(3):581-6 [12270134] Cell. 1992 Feb 21;68(4):673-82 [1739974] Biochem J. 1993 Dec 1;296 ( Pt 2):297-301 [8257416] J Biol Chem. 1994 Feb 18;269(7):5241-8 [8106507] Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1381-5 [7877987] Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9407-11 [7568142] J Biol Chem. 1995 Nov 10;270(45):27179-85 [7592974] J Biol Chem. 1996 Apr 26;271(17):10299-303 [8626598] Science. 1996 Oct 11;274(5285):174-5 [8927976] J Biol Chem. 1997 Feb 14;272(7):4398-403 [9020162] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gestation stage-specific oxidative deoxyribonucleic acid damage from sidestream smoke in pregnant rats and their fetuses. AN - 71430770; 14655905 AB - Transplacental exposure to environmental tobacco smoke (ETS) is a possible cancer risk factor in offspring. The authors exposed pregnant Sprague-Dawley rats to a relevant dose of ETS (1 mg/m3) from gestation day 4 to days 16 or 21. They then assayed tissues for levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG), a marker of oxidative deoxyribonucleic acid damage. ETS exposure ending on gestation day 16 resulted in statistically significant increases in 8-oxo-dG in maternal liver and kidney and in fetal kidney. On gestation day 21, there were significant 8-oxo-dG increases in fetal liver and brain. These gestational stage- and tissue-specific increases of 1.2- to 1.4-fold are similar to the putative relative increases in risk of human cancers related to ETS. JF - Archives of environmental health AU - Maciag, Anna AU - Bialkowska, Aneta AU - Espiritu, Imelda AU - Powell, Douglas AU - Alvord, W Gregory AU - Kasprzak, Kazimierz S AU - Anderson, Lucy M AU - Witschi, Hanspeter R AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. Y1 - 2003/04// PY - 2003 DA - April 2003 SP - 238 EP - 244 VL - 58 IS - 4 SN - 0003-9896, 0003-9896 KW - Tobacco Smoke Pollution KW - 0 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - Deoxyguanosine KW - G9481N71RO KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Maternal-Fetal Exchange KW - Animals KW - Rats, Sprague-Dawley KW - Fetus -- drug effects KW - Liver -- drug effects KW - Brain -- drug effects KW - Kidney -- embryology KW - Kidney -- drug effects KW - Brain -- embryology KW - Female KW - Pregnancy KW - DNA Damage KW - Tobacco Smoke Pollution -- adverse effects KW - Deoxyguanosine -- analysis KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/71430770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gestation+stage-specific+oxidative+deoxyribonucleic+acid+damage+from+sidestream+smoke+in+pregnant+rats+and+their+fetuses.&rft.au=Maciag%2C+Anna%3BBialkowska%2C+Aneta%3BEspiritu%2C+Imelda%3BPowell%2C+Douglas%3BAlvord%2C+W+Gregory%3BKasprzak%2C+Kazimierz+S%3BAnderson%2C+Lucy+M%3BWitschi%2C+Hanspeter+R&rft.aulast=Maciag&rft.aufirst=Anna&rft.date=2003-04-01&rft.volume=58&rft.issue=4&rft.spage=238&rft.isbn=&rft.btitle=&rft.title=Archives+of+environmental+health&rft.issn=00039896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-24 N1 - Date created - 2003-12-05 N1 - Date revised - 2017-01-14 N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Estimation of Linkage and Association from Allele Transmission Data AN - 21130785; 11157501 AB - The TDT provides a hypothesis test for the presence of linkage or association (linkage disequilibrium). However, since the TDT is a single test statistic, it cannot be used to separate association and linkage. The importance of this difficulty, following a significant TDT result, has been recently emphasized by Whittaker, Denham and Morris (2000), who alert the community to the possibility that a significant TDT may result from loose linkage and strong association, or from tight linkage and weak association. To attack this problem we start with the parametric model for family-based allele transmission data of Sham and Curtis (1995) (or Sham (1998)) and find that the parameters in the model are not always identifiable. So we introduce a reparameterization that resolves the identifiability issues and leads to a valid likelihood ratio (LR) test for linkage. Since the linkage and association parameters are both of interest, we next introduce and apply an integrated likelihood (IL) approach to provide separate point estimates and confidence intervals for these parameters. The estimates are shown to have generally small bias and mean square error, while the confidence intervals have good average length and coverage probabilities. We compare the power of the IL approach for testing linkage and, separately association, with the TDT and LR. JF - Biometrical Journal AU - Malley, James D AU - Redner, Richard A AU - Severini, Thomas A AU - Badner, Judith A AU - Pajevic, Sinisa AU - Bailey-Wilson, Joan E AD - Center for Information Technology, National Institutes of Health, jmalley@helix.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 349 EP - 366 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 45 IS - 3 SN - 0323-3847, 0323-3847 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Linkage disequilibrium KW - Data processing KW - Statistics KW - Biometrics KW - DNA nucleotidylexotransferase KW - Models KW - G 07880:Human Genetics KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21130785?accountid=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=Biometrical+Journal&rft.atitle=Estimation+of+Linkage+and+Association+from+Allele+Transmission+Data&rft.au=Malley%2C+James+D%3BRedner%2C+Richard+A%3BSeverini%2C+Thomas+A%3BBadner%2C+Judith+A%3BPajevic%2C+Sinisa%3BBailey-Wilson%2C+Joan+E&rft.aulast=Malley&rft.aufirst=James&rft.date=2003-04-01&rft.volume=45&rft.issue=3&rft.spage=349&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200390017 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Linkage disequilibrium; Statistics; Data processing; Biometrics; Models; DNA nucleotidylexotransferase DO - http://dx.doi.org/10.1002/bimj.200390017 ER - TY - JOUR T1 - Choice of Scores in Trend Tests for Case-Control Studies of Candidate-Gene Associations AN - 21075269; 11132307 AB - When applying the Cochran-Armitage (CA) trend test for an association between a candidate allele and a disease in a case-control study, a set of scores must be assigned to the genotypes. Sasieni (1997, Biometrics 53, 1253-1261) suggested scores for the recessive, additive, and dominant models but did not examine their statistical properties. Using the criteria of minimizing the required sample size of the CA trend test to achieve prespecified type I and type II errors, we show that the scores given by Sasieni (1997) are optimal for the recessive and dominant models and locally optimal for the additive one. Moreover, the additive scores are shown to be locally optimal for the multiplicative model. The tests are applied to a real dataset. JF - Biometrical Journal AU - Zheng, Gang AU - Freidlin, Boris AU - Li, Zhaohai AU - Gastwirth, Joseph L AD - Office of Biostatistics Research, National Heart, Lung and Blood Institute, 6701 Rockledge Drive, MSC 7938, Bethesda, MD 20892, U.S.A., zhengg@nhlbi.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 335 EP - 348 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 45 IS - 3 SN - 0323-3847, 0323-3847 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Statistics KW - Statistical analysis KW - Biometrics KW - Genotypes KW - Models KW - W 30965:Miscellaneous, Reviews KW - G 07780:Fungi UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21075269?accountid=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=Biometrical+Journal&rft.atitle=Choice+of+Scores+in+Trend+Tests+for+Case-Control+Studies+of+Candidate-Gene+Associations&rft.au=Zheng%2C+Gang%3BFreidlin%2C+Boris%3BLi%2C+Zhaohai%3BGastwirth%2C+Joseph+L&rft.aulast=Zheng&rft.aufirst=Gang&rft.date=2003-04-01&rft.volume=45&rft.issue=3&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200390016 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Statistics; Statistical analysis; Genotypes; Biometrics; Models DO - http://dx.doi.org/10.1002/bimj.200390016 ER - TY - JOUR T1 - Issues and progress with protein kinase inhibitors for cancer treatment AN - 20642403; 7964400 AB - Identification of the key roles of protein kinases in cancer has led to extensive efforts to develop kinase inhibitors for the treatment of a wide range of cancers, and more than 30 such agents are now in clinical trials. Here, we consider the crucial issues in the development of kinase inhibitors for cancer, and discuss strategies to address the challenges raised by these issues in the light of preclinical and clinical experiences so far. JF - Nature Reviews: Drug Discovery AU - Dancey, Janet AU - Sausville, Edward A AD - Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program, Investigational Drug Branch, National Cancer Institute, 6130 Executive Blvd, Room 7131, Rockville, Maryland 20852, USA., danceyj@ctep.nci.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 296 EP - 313 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 2 IS - 4 SN - 1474-1784, 1474-1784 KW - Biotechnology Research Abstracts (through 1992) KW - protein kinase inhibitors KW - Clinical trials KW - Cancer KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20642403?accountid=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+Reviews%3A+Drug+Discovery&rft.atitle=Issues+and+progress+with+protein+kinase+inhibitors+for+cancer+treatment&rft.au=Dancey%2C+Janet%3BSausville%2C+Edward+A&rft.aulast=Dancey&rft.aufirst=Janet&rft.date=2003-04-01&rft.volume=2&rft.issue=4&rft.spage=296&rft.isbn=&rft.btitle=&rft.title=Nature+Reviews%3A+Drug+Discovery&rft.issn=14741784&rft_id=info:doi/10.1038%2Fnrd1066 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-03-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; protein kinase inhibitors; Clinical trials DO - http://dx.doi.org/10.1038/nrd1066 ER - TY - JOUR T1 - Engineering of A3 adenosine and P2Y nucleotide receptors and their ligands AN - 20379651; 7761686 AB - Modification of the ribose moiety of nucleotides and nucleosides has provided new insights into structural and conformational requirements for ligands at P2Y nucleotide receptors and at adenosine receptors (ARs). Methanocarba derivatives (containing a rigid bicyclic ring system in place of ribose) of adenosine, ATP, ADP, UTP, UDP, and other receptor agonist analogs were synthesized. Biological evaluation led to the conclusion that in general the Northern (N)-conformation was favored over the Southern (S)-conformation of the pseudoribose moiety at A1 and A3 ARs and at P2Y1, P2Y2, P2Y4, or P2Y11 receptors, but not P2Y6 receptors. At the hA3 AR a new full agonist, MRS1898, the (N)-methanocarba equivalent of Cl-IB-MECA (2-chloro-N6-(3-iodobenzyl)-5'-N-methylcarbamoyladenosine), had a Ki value of 1.9 nM in binding to the hA3 AR expressed in CHO cells. Functional assays confirmed the selectivity of MRS1898, although Cl-IB-MECA was even more functionally selective for human A3 vs. hA1 and hA2A ARs. Thirty µM MRS1898 did not induce apoptosis in HL-60 cells, suggesting that some of the proapoptotic effects of Cl-IB-MECA may be nonreceptor-mediated. Manipulation of the sequence of A3 ARs through site-directed mutagenesis has led to pharmacologically unique constructs: constitutively active receptors and neoceptors. Such engineered receptors may later prove to have potential for cardioprotection through gene transfer. Effects of single amino acid replacement were interpreted using a rhodopsin-based model of ligand-A3 receptor interactions, leading to the proposal that a movement of the conserved W243 in TM6 may be involved in AR activation. JF - Drug Development Research AU - Jacobson, Kenneth A AU - Kim, Hak Sung AU - Ravi, Gnana AU - Kim, Soo-Kyung AU - Lee, Kyeong AU - Chen, Aishe AU - Chen, Wangzhong AU - Kim, Seong Gon AU - Barak, Dov AU - Liang, Bruce T AU - Gao, Zhan-Guo AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, kajacobs@helix.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 330 EP - 339 PB - John Wiley & Sons, 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 58 IS - 4 SN - 0272-4391, 0272-4391 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Site-directed mutagenesis KW - Amino acids KW - Apoptosis KW - Adenosine receptors KW - Gene transfer KW - Purine P2Y receptors KW - Ribose KW - nucleosides KW - ATP KW - Drug development KW - Nucleotides KW - N 14840:Antisense, Nucleotide Analogs KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20379651?accountid=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=Drug+Development+Research&rft.atitle=Engineering+of+A3+adenosine+and+P2Y+nucleotide+receptors+and+their+ligands&rft.au=Jacobson%2C+Kenneth+A%3BKim%2C+Hak+Sung%3BRavi%2C+Gnana%3BKim%2C+Soo-Kyung%3BLee%2C+Kyeong%3BChen%2C+Aishe%3BChen%2C+Wangzhong%3BKim%2C+Seong+Gon%3BBarak%2C+Dov%3BLiang%2C+Bruce+T%3BGao%2C+Zhan-Guo&rft.aulast=Jacobson&rft.aufirst=Kenneth&rft.date=2003-04-01&rft.volume=58&rft.issue=4&rft.spage=330&rft.isbn=&rft.btitle=&rft.title=Drug+Development+Research&rft.issn=02724391&rft_id=info:doi/10.1002%2Fddr.10168 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-12-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Site-directed mutagenesis; Apoptosis; Amino acids; Gene transfer; Adenosine receptors; nucleosides; Ribose; Purine P2Y receptors; ATP; Drug development; Nucleotides DO - http://dx.doi.org/10.1002/ddr.10168 ER - TY - JOUR T1 - Protein microarrays: Meeting analytical challenges for clinical applications AN - 20241129; 5614162 AB - Protein microarrays, one emerging class of proteomic technologies, have broad applications for discovery and quantitative analysis. A rapidly expanding use of this technology is the acquisition of information about the posttranslational modifications of proteins reflecting the activity state of signal pathways and networks, and is now employed for the analysis of biopsy samples in clinical trial research. JF - Cancer Cell AU - Liotta, LA AU - Espina, V AU - Mehta, AI AU - Calvert, V AU - Rosenblatt, K AU - Geho, D AU - Munson, P J AU - Young, L AU - Wulfkuhle, J AU - Petricoin III, EF AD - FDA-NCI Clinical Proteomics Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA, liottal@mail.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 317 EP - 325 VL - 3 IS - 4 SN - 1535-6108, 1535-6108 KW - Biotechnology and Bioengineering Abstracts KW - Protein arrays KW - Therapeutic applications KW - Biopsy KW - proteomics KW - Clinical trials KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20241129?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Cell&rft.atitle=Protein+microarrays%3A+Meeting+analytical+challenges+for+clinical+applications&rft.au=Liotta%2C+LA%3BEspina%2C+V%3BMehta%2C+AI%3BCalvert%2C+V%3BRosenblatt%2C+K%3BGeho%2C+D%3BMunson%2C+P+J%3BYoung%2C+L%3BWulfkuhle%2C+J%3BPetricoin+III%2C+EF&rft.aulast=Liotta&rft.aufirst=LA&rft.date=2003-04-01&rft.volume=3&rft.issue=4&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Cancer+Cell&rft.issn=15356108&rft_id=info:doi/10.1016%2FS1535-6108%2803%2900086-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-09-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Protein arrays; Therapeutic applications; Biopsy; proteomics; Clinical trials DO - http://dx.doi.org/10.1016/S1535-6108(03)00086-2 ER - TY - JOUR T1 - Bone marrow stem cells regenerate infarcted myocardium AN - 19954320; 6622689 AB - Heart disease is the leading cause of death in the United States for both men and women. Nearly 50% of all cardiovascular deaths result from coronary artery disease. Occlusion of the left coronary artery leads to ischemia, infarction, necrosis of the affected myocardial tissue followed by scar formation and loss of function. Although myocytes in the surviving myocardium undergo hypertrophy and cell division occurs in the border area of the dead tissue, myocardial infarcts do not regenerate and eventually result in the death of the individual. Numerous attempts have been made to repair damaged myocardium in animal models and in humans. Bone marrow stem cells (BMSC) retain the ability throughout adult life to self-renew and differentiate into cells of all blood lineages. These adult BMSC have recently been shown to have the capacity to differentiate into multiple specific cell types in tissues other than bone marrow. Our research is focused on the capacity of BMSC to form new cardiac myocytes and coronary vessels following an induced myocardial infarct in adult mice. In this paper we will review the data we have previously published from studies on the regenerative capacity of BMSC in acute ischemic myocardial injury. In one experiment donor BMSC were injected directly into the healthy myocardium adjacent to the injured area of the left ventricle. In the second experiment, mice were treated with cytokines to mobilize their BMSC into the circulation on the theory that the stem cells would traffic to the myocardial infarct. In both experimental protocols, the BMSC gave rise to new cardiac myocytes and coronary blood vessels. This BMSC-derived myocardial regeneration resulted in improved cardiac function and survival. JF - Pediatric Transplantation AU - Orlic, Donald AU - Kajstura, Jan AU - Chimenti, Stefano AU - Bodine, David M AU - Leri, Annarosa AU - Anversa, Piero AD - Genetics and Molecular Biology Branch, NHGRI, NIH, Bethesda, MD 20892, dorlic@nhgri.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 86 EP - 88 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 7 IS - s3 SN - 1397-3142, 1397-3142 KW - Biotechnology and Bioengineering Abstracts KW - Heart KW - Myocytes KW - Data processing KW - Injuries KW - Bone marrow KW - Animal models KW - Ischemia KW - cardiomyocytes KW - Myocardial infarction KW - coronary artery KW - Ventricle KW - Cell division KW - Stem cells KW - Necrosis KW - Hypertrophy KW - Blood vessels KW - Reviews KW - Occlusion KW - Regeneration KW - Cytokines KW - Infarction KW - Heart diseases KW - Myocardium KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19954320?accountid=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=Pediatric+Transplantation&rft.atitle=Bone+marrow+stem+cells+regenerate+infarcted+myocardium&rft.au=Orlic%2C+Donald%3BKajstura%2C+Jan%3BChimenti%2C+Stefano%3BBodine%2C+David+M%3BLeri%2C+Annarosa%3BAnversa%2C+Piero&rft.aulast=Orlic&rft.aufirst=Donald&rft.date=2003-04-01&rft.volume=7&rft.issue=s3&rft.spage=86&rft.isbn=&rft.btitle=&rft.title=Pediatric+Transplantation&rft.issn=13973142&rft_id=info:doi/10.1034%2Fj.1399-3046.7.s3.13.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-07-01 N1 - SuppNotes - References, 14. N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Heart; Myocytes; Data processing; Injuries; Animal models; Bone marrow; cardiomyocytes; Ischemia; Myocardial infarction; coronary artery; Hypertrophy; Necrosis; Stem cells; Cell division; Ventricle; Blood vessels; Occlusion; Reviews; Regeneration; Cytokines; Infarction; Myocardium; Heart diseases DO - http://dx.doi.org/10.1034/j.1399-3046.7.s3.13.x ER - TY - JOUR T1 - Human Oral Cavity as a Model for the Study of Genome-Genome Interactions AN - 19807984; 5675267 AB - The enormous diversity of culturable bacteria within the oral microbial community coupled with experimental accessibility renders the human oral cavity a valuable model to investigate genome-genome interactions. The complex interactions of oral bacteria result in the formation of biofilms on the surfaces of the oral cavity. One mechanism thought to be important in biofilm formation is the coaggregation of bacterial partners. In this paper, we examine the role of coaggregation in oral biofilms and develop protocols to elucidate the spatial organization of bacterial species retained within oral biofilms. To explore these issues, we have employed two experimental systems: the saliva-coated flowcell and the retrievable enamel chip. From flowcell studies, we have determined that coaggregation can greatly influence the ability of an oral bacterial species to grow and be retained within the developing biofilm. To examine the spatial architecture of oral biofilms, fluorescent in situ hybridization protocols were developed that successfully target specific members of the oral microbial community. Together, these approaches provide insight into the development of oral biofilms and expand our understanding of genome-genome interactions. JF - Biological Bulletin, Marine Biological Laboratory, Woods Hole AU - Foster, J S AU - Palmer, RJ Jr AU - Kolenbrander, P E AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 30, Room 310, 30 Convent Drive MSC 4350, Bethesda, MD 20892-4350, USA, pkolenbrander@dir.nidcr.nih.gov Y1 - 2003/04/01/ PY - 2003 DA - 2003 Apr 01 SP - 200 EP - 204 PB - Marine Biological Laboratory VL - 204 IS - 2 SN - 0006-3185, 0006-3185 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Enamel KW - Biofilms KW - Oral cavity KW - Models KW - Fluorescence in situ hybridization KW - J 02320:Cell Biology KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19807984?accountid=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=Biological+Bulletin%2C+Marine+Biological+Laboratory%2C+Woods+Hole&rft.atitle=Human+Oral+Cavity+as+a+Model+for+the+Study+of+Genome-Genome+Interactions&rft.au=Foster%2C+J+S%3BPalmer%2C+RJ+Jr%3BKolenbrander%2C+P+E&rft.aulast=Foster&rft.aufirst=J&rft.date=2003-04-01&rft.volume=204&rft.issue=2&rft.spage=200&rft.isbn=&rft.btitle=&rft.title=Biological+Bulletin%2C+Marine+Biological+Laboratory%2C+Woods+Hole&rft.issn=00063185&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Enamel; Biofilms; Oral cavity; Fluorescence in situ hybridization; Models ER - TY - JOUR T1 - Handling of Clinical Tissue Specimens for Molecular Profiling Studies AN - 18814242; 5679386 AB - The relationship between gene expression profiles and cellular phenotypes is an important aspect of functional genomics. Clinical tissue specimens will play a vital role in this effort. The usefulness of tissue for molecular profiling is significantly influenced by the manner of specimen handling. Crucial components of this process include the optimization of the methods of tissue fixation and embedding, not only to obtain excellent histological detail, but also to promote the elucidation of the gene and protein expression profiles. In this article, we describe handling of clinical specimens using whole-mount prostate as an example, the use of new high-throughput techniques that allow molecular profiling analysis and the use of a web-based 3-dimensional model to combine these data to make it available to clinicians and the research community. Complete protocols and additional discussion are available on the website, http://cgapmf.nih.gov. JF - Current Issues in Molecular Biology AU - Leiva, I M AU - Emmert-Buck, M R AU - Gillespie, J W AD - Pathogenetics Unit, Laboratory of Pathology and Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, ileiva@med.puc.cl Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 27 EP - 35 VL - 5 IS - 2 SN - 1467-3037, 1467-3037 KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - G 07439:General - reviews/ethics, etc. 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/18814242?accountid=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+Issues+in+Molecular+Biology&rft.atitle=Handling+of+Clinical+Tissue+Specimens+for+Molecular+Profiling+Studies&rft.au=Leiva%2C+I+M%3BEmmert-Buck%2C+M+R%3BGillespie%2C+J+W&rft.aulast=Leiva&rft.aufirst=I&rft.date=2003-04-01&rft.volume=5&rft.issue=2&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Current+Issues+in+Molecular+Biology&rft.issn=14673037&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Webcasting Videoconferences Over IP: A Synchronous Communication Experiment AN - 18784010; 5649048 AB - A multipoint videoconference was webcast live to an audience who could communicate with conference panelists and each other via chat. The videoconference, webcast, and chat were done entirely over the Internet. Seven panelists at four conference sites that had Internet2 connectivity and were located in different time zones within the continental United States discussed the topic of "Evaluating Health Professions Education and Information Resources on the Web." This discussion was broadcast to individuals and groups at various U.S. locations who had expressed an interest in the topic and had sufficient connectivity for receiving the video stream. Webcast recipients could log on a chat server and type questions and comments to the panelists and other viewers. The experiment's rationale, procedures, and outcomes are described, and issues associated with the use of the technologies are identified. JF - Journal of the American Medical Informatics Association AU - Locatis, C AU - Fontelo, P AU - Sneiderman, C AU - Ackerman, M AU - Uijtdehaage, S AU - Candler, C AU - Stensaas, S AU - Dennis, S AD - National Library of Medicine, Building 38A, Room B1N-30F, 8600 Rockville Pike, Bethesda, MD 20894, USA, Locatic@nlm.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 150 EP - 153 PB - American Medical Informatics Association, 4915 St. Elmo Ave. Suite 401 Bethesda MD 20814 USA, [mailto:mail@mail.amia.org], [URL:http://www.amia.org] VL - 10 IS - 2 SN - 1067-5027, 1067-5027 KW - Internet KW - videoconferences KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18784010?accountid=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+American+Medical+Informatics+Association&rft.atitle=Webcasting+Videoconferences+Over+IP%3A+A+Synchronous+Communication+Experiment&rft.au=Locatis%2C+C%3BFontelo%2C+P%3BSneiderman%2C+C%3BAckerman%2C+M%3BUijtdehaage%2C+S%3BCandler%2C+C%3BStensaas%2C+S%3BDennis%2C+S&rft.aulast=Locatis&rft.aufirst=C&rft.date=2003-04-01&rft.volume=10&rft.issue=2&rft.spage=150&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Informatics+Association&rft.issn=10675027&rft_id=info:doi/10.1197%2Fjamia.M1170 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1197/jamia.M1170 ER - TY - JOUR T1 - Assessing Human Polychlorinated Biphenyl Contamination for Epidemiologic Studies: Lessons from Patterns of Congener Concentrations in Canadians in 1992 AN - 18782019; 5650358 AB - Humans are always exposed to mixtures of polychlorinated biphenyls (PCBs), so assessment of their health effects is complicated. Because the original sources are relatively standard mixtures that change in predictable ways while traversing the environment, there is substantial uniformity in the congener mixtures people carry. To the extent that concentrations are highly correlated, measuring multiple congeners within correlated groups would be unnecessary and estimation of separate biologic effects would be impossible. We examined correlation patterns in previously collected data on 38 congeners (and 14 other organochlorines) from 497 human milk samples from Canada from 1992. Congeners 138, 153, 156, 157, 170, 183, 187, 194, 199, and 203 were highly intercorrelated; 180 had slightly lower correlations with this group. Congeners 74, 105, and 118 were highly intercorrelated and moderately to highly correlated with the first group. Congener 99 had moderate correlations with both these groups, and congener 66 had lesser correlations with the primary group. In contrast, congeners 28, 44, 49, 60, 90/101, 128, 137, and 193 showed little correlation with any other congeners. The remaining 14 congeners were uninformative; they were quantified in fewer than 30% of samples, and varying lipid concentrations meant that those quantified were not necessarily at higher concentrations than those not quantified. In study of human health effects of PCBs, the congener pattern present in the population under study should be examined when deciding which congeners to measure; instead of solely redundant or uninformative congeners, attention should be given to other congeners that may be more useful in addressing the question of interest. JF - Environmental Health Perspectives AU - Gladen, B C AU - Doucet, J AU - Hansen, L G AD - Biostatistics Branch, Mail Drop A3-03, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709 USA, gladen@niehs.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 437 EP - 443 VL - 111 IS - 4 SN - 0091-6765, 0091-6765 KW - congeners KW - man KW - Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - X 24190:Polycyclic hydrocarbons KW - H 12000:Epidemiology and Public Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18782019?accountid=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=Assessing+Human+Polychlorinated+Biphenyl+Contamination+for+Epidemiologic+Studies%3A+Lessons+from+Patterns+of+Congener+Concentrations+in+Canadians+in+1992&rft.au=Gladen%2C+B+C%3BDoucet%2C+J%3BHansen%2C+L+G&rft.aulast=Gladen&rft.aufirst=B&rft.date=2003-04-01&rft.volume=111&rft.issue=4&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Fehp.5858 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1289/ehp.5858 ER - TY - JOUR T1 - Additive Effect of Smoking and Cotton Dust Exposure on Respiratory Symptoms and Pulmonary Function of Cotton Textile Workers AN - 18777954; 5642265 AB - One hundred and sixty-nine and 175 cotton textile workers (CTWs) were enrolled in the first (1991) and second (1996) surveys to investigate the prevalence of byssinosis. The synergistic effect of smoking on cotton dust exposure was also evaluated. Although the difference in prevalence of abnormal pulmonary function between the first (38.5%) and second study (38.9%) was not statistically significant, smokers had significantly higher frequency than nonsmokers in both surveys. A significant trend existed between the cotton dust levels and the frequency of abnormal lung function. The significant trend was also noted in both smokers and nonsmokers. The frequency of respiratory symptoms and the prevalence of severe byssinosis in the second survey (14.9% and 12.6%, respectively) were significantly lower than that in the first survey (39.7% and 21.9%, respectively). The reduction of symptoms was due to remodeling of this old cotton mill. The prevalences of respiratory symptoms and byssinosis in smokers being significantly higher than in nonsmokers only found in the first survey, but not found in the second survey. These results indicate that smoking potentiates the effect of cotton dust exposure on respiratory symptoms and byssinosis. The second study reveals high prevalence of byssinosis still existed in Taiwanese cotton mill, although the prevalence was declining. Smoking was found to show an additive effect on cotton dust exposure. Anti-smoking campaign, occupational health program to reduce the dust exposure, and periodical medical examination are measures to prevent from byssinosis. JF - Industrial Health AU - Su, Yih-Ming AU - Su, Jenn-Rong AU - Sheu, Jia-Yih AU - Loh, Ching-Hui AU - Liou, Saou-Hsing AD - School of Public Health, National Defense Medical Center, National Defense University, 161 Ming-Chun East Rd, Sec. 6, Nei-Hu, Taipei, Taiwan, 114, R.O.C. Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 109 EP - 115 VL - 41 IS - 2 SN - 0019-8366, 0019-8366 KW - byssinosis KW - man KW - Health & Safety Science Abstracts; Pollution Abstracts; Toxicology Abstracts KW - H 1000:Occupational Safety and Health KW - P 6000:TOXICOLOGY AND HEALTH KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18777954?accountid=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=Industrial+Health&rft.atitle=Additive+Effect+of+Smoking+and+Cotton+Dust+Exposure+on+Respiratory+Symptoms+and+Pulmonary+Function+of+Cotton+Textile+Workers&rft.au=Su%2C+Yih-Ming%3BSu%2C+Jenn-Rong%3BSheu%2C+Jia-Yih%3BLoh%2C+Ching-Hui%3BLiou%2C+Saou-Hsing&rft.aulast=Su&rft.aufirst=Yih-Ming&rft.date=2003-04-01&rft.volume=41&rft.issue=2&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Industrial+Health&rft.issn=00198366&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Induction of Tolerance to a Recombinant Human Enzyme, Acid Alpha-Glucosidase, in Enzyme Deficient Knockout Mice AN - 18776434; 5645242 AB - When knockout mice are used to test the efficacy of recombinant human proteins, the animals often develop antibodies to the enzyme, precluding long-term pre-clinical studies. This has been a problem with a number of models, for example, the evaluation of gene or enzyme replacement therapies in a knockout model of glycogen storage disease type II (GSDII; Pompe syndrome). In this disease, the lack of acid alpha-glucosidase (GAA) results in lysosomal accumulation of glycogen, particularly in skeletal and cardiac muscle. Here, we report that in a GAA-deficient mouse model of GSDII, low levels of transgene-encoded human GAA expressed in skeletal muscle or liver dramatically blunt or abolish the immune response to human recombinant protein. Of two low expression transgenic lines, only the liver-expressing line exhibited a profound GAA deficiency in skeletal muscle and heart indistinguishable from that in the original knockouts. The study suggests that the induction of tolerance in animal models of protein deficiencies could be achieved by restricting the expression of a gene of interest to a particular, carefully chosen tissue. JF - Transgenic Research AU - Raben, N AU - Nagaraju, K AU - Lee, A AU - Lu, N AU - Rivera, Y AU - Jatkar, T AU - Hopwood, J J AU - Plotz, PH AD - Arthritis and Rheumatism Branch, NIAMS, National Institutes of Health, 9000 Rockville Pike, Clinical Center Bld. 10/9N244, Bethesda, MD 20892, USA, rabenn@arb.niams.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 171 EP - 178 VL - 12 IS - 2 SN - 0962-8819, 0962-8819 KW - Pompe syndrome KW - glycogen storage disease II KW - knockout mice KW - man KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - W3 33310:Enzymes and cofactors KW - G 07444:Animal models KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18776434?accountid=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=Transgenic+Research&rft.atitle=Induction+of+Tolerance+to+a+Recombinant+Human+Enzyme%2C+Acid+Alpha-Glucosidase%2C+in+Enzyme+Deficient+Knockout+Mice&rft.au=Raben%2C+N%3BNagaraju%2C+K%3BLee%2C+A%3BLu%2C+N%3BRivera%2C+Y%3BJatkar%2C+T%3BHopwood%2C+J+J%3BPlotz%2C+PH&rft.aulast=Raben&rft.aufirst=N&rft.date=2003-04-01&rft.volume=12&rft.issue=2&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Transgenic+Research&rft.issn=09628819&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 - Pathogenesis and potential antiviral therapy of complications of smallpox vaccination AN - 18773405; 5643792 AB - Vaccination against smallpox may result in a variety of complications, ranging in severity from benign to lethal. Universal vaccination was halted in the US in 1972, so almost half the present population has never been vaccinated. Because side effects occur most often in first-time vaccinees, current plans for rapid large-scale vaccination in the event of bioterrorist attack raise concerns about the occurrence of a large number of adverse events. Most complications result from the excessive replication of vaccinia virus, making them potential targets for antiviral therapy. Effective treatment is especially needed for persons with atopic dermatitis or eczema, who are unusually susceptible to the initiation and spread of vaccinia infection because of defects of innate immunity in the skin, and for individuals with defective cell-mediated immunity, who are unable to eliminate vaccinia infection once it has begun. In the past, many complications were treated with vaccinia immune globulin (VIG) and/or the antiviral drug methisazone, but neither was tested in placebo-controlled trials. New antiviral drugs are now available, but have not yet been evaluated for treating vaccinia infections in humans. Both laboratory research and clinical studies are needed to help prevent serious complications in any major vaccination campaign. JF - Antiviral Research AU - Bray, M AD - Biodefense Clinical Research Branch, Office of Clinical Research, Office of the Director, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 101 EP - 114 VL - 58 IS - 2 SN - 0166-3542, 0166-3542 KW - bioterrorism KW - methisazone KW - smallpox virus KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - W4 240:Bioterrorism & Biological Warfare KW - V 22100:Antiviral agents KW - A 01097:Viruses KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18773405?accountid=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=Pathogenesis+and+potential+antiviral+therapy+of+complications+of+smallpox+vaccination&rft.au=Bray%2C+M&rft.aulast=Bray&rft.aufirst=M&rft.date=2003-04-01&rft.volume=58&rft.issue=2&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Antiviral+Research&rft.issn=01663542&rft_id=info:doi/10.1016%2FS0166-3542%2803%2900008-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0166-3542(03)00008-1 ER - TY - JOUR T1 - Regulatory roles for small RNAs in bacteria AN - 18771354; 5640431 AB - Small RNAs can act to regulate both the synthesis of proteins, by affecting mRNA transcription, translation and stability, and the activity of specific proteins by binding to them. As a result of recent genome-wide screens, around 50 small RNAs have now been identified in Escherichia coli. These include many that require the RNA-binding protein Hfq for their activity; most of these RNAs act by pairing with their target mRNAs. Small RNAs can both positively and negatively regulate translation, can simultaneously regulate multiple mRNA targets, and can change the pattern of polarity within an operon. JF - Current Opinion in Microbiology AU - Masse, E AU - Majdalani, N AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA, susang@helix.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 120 EP - 124 VL - 6 IS - 2 SN - 1369-5274, 1369-5274 KW - Hfq protein KW - sRNA KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02726:RNA and ribosomes KW - N 14100:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18771354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Microbiology&rft.atitle=Regulatory+roles+for+small+RNAs+in+bacteria&rft.au=Masse%2C+E%3BMajdalani%2C+N%3BGottesman%2C+S&rft.aulast=Masse&rft.aufirst=E&rft.date=2003-04-01&rft.volume=6&rft.issue=2&rft.spage=120&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Microbiology&rft.issn=13695274&rft_id=info:doi/10.1016%2FS1369-5274%2803%2900027-4 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S1369-5274(03)00027-4 ER - TY - JOUR T1 - Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning AN - 18756708; 5614784 AB - Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies. Its high mortality rate is mainly a result of intra-hepatic metastases. We analyzed the expression profiles of HCC samples without or with intra-hepatic metastases. Using a supervised machine-learning algorithm, we generated for the first time a molecular signature that can classify metastatic HCC patients and identified genes that were relevant to metastasis and patient survival. We found that the gene expression signature of primary HCCs with accompanying metastasis was very similar to that of their corresponding metastases, implying that genes favoring metastasis progression were initiated in the primary tumors. Osteopontin, which was identified as a lead gene in the signature, was over-expressed in metastatic HCC; an osteopontin-specific antibody effectively blocked HCC cell invasion in vitro and inhibited pulmonary metastasis of HCC cells in nude mice. Thus, osteopontin acts as both a diagnostic marker and a potential therapeutic target for metastatic HCC. JF - Nature Medicine AU - Ye, Qing-Hai AU - Qin, Lun-Xiu AU - Forgues, M AU - He, Ping AU - Kim, Jin Woo AU - Peng, A C AU - Simon, R AU - Li, Yan AU - Robles, AI AU - Chen, Yidong AU - Ma, Zeng-Chen AU - Wu, Zhi-Quan AU - Ye, Sheng-Long AU - Wang, Xin Wei AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA, xw3u@nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 416 EP - 423 VL - 9 IS - 4 SN - 1078-8956, 1078-8956 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts; Virology & AIDS Abstracts KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W 30965:Miscellaneous, Reviews KW - V 22121:Diagnosis KW - W3 33130:Genetic based (PCR, etc.) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18756708?accountid=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=Predicting+hepatitis+B+virus-positive+metastatic+hepatocellular+carcinomas+using+gene+expression+profiling+and+supervised+machine+learning&rft.au=Ye%2C+Qing-Hai%3BQin%2C+Lun-Xiu%3BForgues%2C+M%3BHe%2C+Ping%3BKim%2C+Jin+Woo%3BPeng%2C+A+C%3BSimon%2C+R%3BLi%2C+Yan%3BRobles%2C+AI%3BChen%2C+Yidong%3BMa%2C+Zeng-Chen%3BWu%2C+Zhi-Quan%3BYe%2C+Sheng-Long%3BWang%2C+Xin+Wei&rft.aulast=Ye&rft.aufirst=Qing-Hai&rft.date=2003-04-01&rft.volume=9&rft.issue=4&rft.spage=416&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/10.1038%2Fnm843 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/nm843 ER - TY - JOUR T1 - Taming ricin toxin AN - 18750868; 5617140 AB - Ricin is a potent toxin once famously delivered on the tip of an umbrella to assassinate a bothersome Bulgarian journalist. Ricin's cytocidal properties have also been exploited in cancer treatment in which the toxin is hooked up to antibodies that specifically target tumor cells. Such immunotoxin conjugates have not yet reached their full potential in the clinic because of 'vascular leak syndrome,' a side effect resulting from endothelial damage that causes fluid to escape from the bloodstream into the lungs, muscle, brain, and other tissues. In this issue, Vitetta and colleagues show that a single point mutation in ricin toxin can eliminate vascular leak syndrome without compromising the toxin's enzymatic action. Moreover, they construct a mutant immunotoxin that is tolerated at higher doses in mice and thereby leads to improved antitumor activity. JF - Nature Biotechnology AU - Kreitman, R J AD - Clinical Immunotherapy Section, Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA, kreitmar@mail.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 372 EP - 374 VL - 21 IS - 4 SN - 1087-0156, 1087-0156 KW - immunotoxins KW - mice KW - vascular leak syndrome KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Toxicology Abstracts; Bioengineering Abstracts KW - X 24172:Plants KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33390:Products: Others KW - W4 120:Genetic Engineering in Medicine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18750868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Taming+ricin+toxin&rft.au=Kreitman%2C+R+J&rft.aulast=Kreitman&rft.aufirst=R&rft.date=2003-04-01&rft.volume=21&rft.issue=4&rft.spage=372&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Stimulus representation in SOP: I. Theoretical rationalization and some implications AN - 18737125; 5617471 AB - The SOP model [Information Processing in Animals: Memory Mechanisms, Erlbaum, Hillsdale, NJ, 1981, p. 5] is described in terms of its assumed stimulus representation, network characteristics, and rules for learning and performance. It is shown how several Pavlovian conditioning phenomena can be accounted on the basis of the model's presumed stimulus representation. Challenges to the SOP model prompted the adoption of a componential stimulus representation in: AESOP [Contemporary Learning Theories: Pavlovian Conditioning and the Status of Traditional Learning Theory, Erlbaum, Hillsdale, NJ, 1989, p. 149], this was a dual representation of the unconditioned stimulus (US), and C- SOP [Contemporary Learning: Theory and Application, Erlbaum, Mahwah, NJ, 2001, p. 23], this was a multi-component representation of the conditioned stimulus (CS). The assumption of a componential CS representation, where large numbers of elements can be separately learned about, necessitated a modification of the learning rule. The modified, 'constrained' rule was found useful to explain timing characteristics of Pavlovian conditioned responses, as well as data offered by Rescorla [J. Exp. Psychol. Anim. Behav. Process. 26 (2000) 428; Q. J. Exp. Psychol. 54B (2001) 53; J. Exp. Psychol. Anim. Behav. Process. 28 (2002) 163] showing that stimuli trained in compound do not share the same quantitative fate. JF - Behavioural Processes AU - Brandon, SE AU - Vogel, E H AU - Wagner, A R AD - Department of Psychology, Yale University, American Psychological Association, 750 First Street NE, Washington, DC 20002-4242, USA, sbrandon@mail.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 5 EP - 25 VL - 62 IS - 1-3 SN - 0376-6357, 0376-6357 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Animal Behavior Abstracts KW - Y 25841:General KW - W4 340:Neurocomputing & Neural Networks KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18737125?accountid=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=Behavioural+Processes&rft.atitle=Stimulus+representation+in+SOP%3A+I.+Theoretical+rationalization+and+some+implications&rft.au=Brandon%2C+SE%3BVogel%2C+E+H%3BWagner%2C+A+R&rft.aulast=Brandon&rft.aufirst=SE&rft.date=2003-04-01&rft.volume=62&rft.issue=1-3&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Behavioural+Processes&rft.issn=03766357&rft_id=info:doi/10.1016%2FS0376-6357%2803%2900016-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0376-6357(03)00016-0 ER - TY - JOUR T1 - Group A Streptococcus Gene Expression in Humans and Cynomolgus Macaques with Acute Pharyngitis AN - 18708483; 5591335 AB - The molecular mechanisms used by group A Streptococcus (GAS) to survive on the host mucosal surface and cause acute pharyngitis are poorly understood. To provide new information about GAS host-pathogen interactions, we used real- time reverse transcription-PCR (RT-PCR) to analyze transcripts of 17 GAS genes in throat swab specimens taken from 18 pediatric patients with pharyngitis. The expression of known and putative virulence genes and regulatory genes (including genes in seven two-component regulatory systems) was studied. Several known and previously uncharacterized GAS virulence gene regulators were highly expressed compared to the constitutively expressed control gene proS. To examine in vivo gene transcription in a controlled setting, three cynomolgus macaques were infected with strain MGAS5005, an organism that is genetically representative of most serotype M1 strains recovered from pharyngitis and invasive disease episodes in North America and Western Europe. These three animals developed clinical signs and symptoms of GAS pharyngitis and seroconverted to several GAS extracellular proteins. Real-time RT-PCR analysis of throat swab material collected at intervals throughout a 12-day infection protocol indicated that expression profiles of a subset of GAS genes accurately reflected the profiles observed in the human pediatric patients. The results of our study demonstrate that analysis of in vivo GAS gene expression is feasible in throat swab specimens obtained from infected human and nonhuman primates. In addition, we conclude that the cynomolgus macaque is a useful nonhuman primate model for the study of molecular events contributing to acute pharyngitis caused by GAS. JF - Infection and Immunity AU - Virtaneva, K AU - Graham, M R AU - Porcella, S F AU - Hoe, N P AU - Su, H AU - Graviss, E A AU - Gardner, T J AU - Allison, JE AU - Lemon, W J AU - Bailey, J R AU - Parnell, MJ AU - Musser, J M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840, jmusser@niaid.nih.gov Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 2199 EP - 2207 VL - 71 IS - 4 SN - 0019-9567, 0019-9567 KW - streptococci KW - Microbiology Abstracts B: Bacteriology KW - J 02841:Microflora UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18708483?accountid=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=Group+A+Streptococcus+Gene+Expression+in+Humans+and+Cynomolgus+Macaques+with+Acute+Pharyngitis&rft.au=Virtaneva%2C+K%3BGraham%2C+M+R%3BPorcella%2C+S+F%3BHoe%2C+N+P%3BSu%2C+H%3BGraviss%2C+E+A%3BGardner%2C+T+J%3BAllison%2C+JE%3BLemon%2C+W+J%3BBailey%2C+J+R%3BParnell%2C+MJ%3BMusser%2C+J+M&rft.aulast=Virtaneva&rft.aufirst=K&rft.date=2003-04-01&rft.volume=71&rft.issue=4&rft.spage=2199&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/10.1128%2FIAI.71.4.2199-2207.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/IAI.71.4.2199-2207.2003 ER - TY - JOUR T1 - A Replication Competent Adenovirus 5 Host Range Mutant-Simian Immunodeficiency Virus (SIV) Recombinant Priming/Subunit Protein Boosting Vaccine Regimen Induces Broad, Persistent SIV-Specific Cellular Immunity to Dominant and Subdominant Epitopes in Mamu-A*01 Rhesus Macaques AN - 18707861; 5597850 AB - CTL are important in controlling HIV and SIV infection. To quantify cellular immune responses induced by immunization, CD8 super(+) T cells specific for the subdominant Env p15m and p54m epitopes and/or the dominant Gag p11C epitope were evaluated by tetramer staining in nine macaques immunized with an adenovirus (Ad) 5 host range mutant (Ad5hr)-SIVenv/rev recombinant and in four of nine which also received an Ad5hr-SIVgag recombinant. Two Ad5hr-SIV recombinant priming immunizations were followed by two boosts with gp120 protein or an envelope polypeptide representing the CD4 binding domain. Two mock-immunized macaques served as controls. IFN- gamma -secreting cells were also assessed by ELISPOT assay using p11C, p15m, and p54m peptide stimuli and overlapping pooled Gag and Env peptides. As shown by tetramer staining, Ad-recombinant priming elicited a high frequency of persistent CD8 super(+) T cells able to recognize p11C, p15m, and p54m epitopes. The presence of memory cells 38 wk postinitial immunization was confirmed by expansion of tetramer-positive CD8 super(+) T cells following in vitro stimulation. The SIV-specific CD8 super(+) T cells elicited were functional and secreted IFN- gamma in response to SIV peptide stimuli. Although the level and frequency of response of peripheral blood CD8 super(+) T cells to the subdominant Env epitopes were not as great as those to the dominant p11C epitope, elevated responses were observed when lymph node CD8 super(+) T cells were evaluated. Our data confirm the potency and persistence of functional cellular immune responses elicited by replication competent Ad-recombinant priming. The cellular immunity elicited is broad and extends to subdominant epitopes. JF - Journal of Immunology AU - Malkevitch, N AU - Patterson, L J AU - Aldrich, K AU - Richardson, E AU - Alvord, W G AU - Robert-Guroff, M AD - Basic Research Laboratory, National Cancer Institute, Bethesda, MD 20892 Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 4281 EP - 4289 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 170 IS - 8 SN - 0022-1767, 0022-1767 KW - CD8 antigen KW - Rhesus macaque KW - Rhesus monkey KW - SIV KW - epitopes KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18707861?accountid=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=A+Replication+Competent+Adenovirus+5+Host+Range+Mutant-Simian+Immunodeficiency+Virus+%28SIV%29+Recombinant+Priming%2FSubunit+Protein+Boosting+Vaccine+Regimen+Induces+Broad%2C+Persistent+SIV-Specific+Cellular+Immunity+to+Dominant+and+Subdominant+Epitopes+in+Mamu-A*01+Rhesus+Macaques&rft.au=Malkevitch%2C+N%3BPatterson%2C+L+J%3BAldrich%2C+K%3BRichardson%2C+E%3BAlvord%2C+W+G%3BRobert-Guroff%2C+M&rft.aulast=Malkevitch&rft.aufirst=N&rft.date=2003-04-01&rft.volume=170&rft.issue=8&rft.spage=4281&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 ER - TY - JOUR T1 - Expression of malaria transmission-blocking vaccine antigen Pfs25 in Pichia pastoris for use in human clinical trials AN - 18692510; 5585712 AB - In previously published studies, Saccharomyces cerevisiae recombinant protein expression systems have been employed to express the malaria parasite antigen Pfs25, a candidate transmission-blocking vaccine antigen against Plasmodium falciparum malaria. However, despite having been in two Phase 1 trials, the recombinant Pfs25 so produced (previously called TBV25H) exists as a mixture of two monomeric protein conformational forms, Pfs25H-A and Pfs25H-B. In this study, we optimized the expression and purification of the two Pfs25H conformers in S. cerevisiae, and characterized their biochemical and antigenic properties, immunogenicities, and transmission-blocking activities. Pfs25H-A is apparently homogeneous, and has the correct conformation as measured by monoclonal antibody recognition. It is, however, expressed at a low yield of only 0.19 mg/l. By contrast, Pfs25H-B is produced as a heterogeneous population of molecules that do not seem to have the correct conformation. Nonetheless, both forms appear equally effective in their ability to produce transmission- blocking antibodies in mice. To address the low yield seen with S. cerevisiae, we also expressed Pfs25 in Pichia pastoris. P. pastoris is apparently superior to S. cerevisiae in producing higher yield, immunologically more potent, biologically more active Pfs25H-A. JF - Vaccine AU - Zou, L AU - Miles, A P AU - Wang, J AU - Stowers, A W AD - Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA, anthony_stowers@csl.com.au Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 1650 EP - 1657 PB - Elsevier Science Ltd. VL - 21 IS - 15 SN - 0264-410X, 0264-410X KW - Pfs25 antigen KW - clinical trials KW - man KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - K 03086:Immunology & vaccination KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18692510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Expression+of+malaria+transmission-blocking+vaccine+antigen+Pfs25+in+Pichia+pastoris+for+use+in+human+clinical+trials&rft.au=Zou%2C+L%3BMiles%2C+A+P%3BWang%2C+J%3BStowers%2C+A+W&rft.aulast=Zou&rft.aufirst=L&rft.date=2003-04-01&rft.volume=21&rft.issue=15&rft.spage=1650&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2FS0264-410X%2802%2900701-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0264-410X(02)00701-6 ER - TY - JOUR T1 - Can transcriptome size be estimated from SAGE catalogs? AN - 18683993; 5579362 AB - SAGE (Serial Analysis of Gene Expression) can be used to estimate the number of unique transcripts in a transcriptome. A simple estimator that corrects for sequencing and sampling errors was applied to a SAGE library (137 832 tags) obtained from mouse embryonic stem cells, and also to Monte Carlo simulated libraries generated using assumed distributions of 'true' expression levels consistent with the data. JF - Bioinformatics AU - Stern, MD AU - Anisimov, S V AU - Boheler, K R AD - Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA Y1 - 2003/04// PY - 2003 DA - Apr 2003 SP - 443 EP - 448 VL - 19 IS - 4 SN - 1367-4803, 1367-4803 KW - serial analysis of gene expression KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18683993?accountid=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=Can+transcriptome+size+be+estimated+from+SAGE+catalogs%3F&rft.au=Stern%2C+MD%3BAnisimov%2C+S+V%3BBoheler%2C+K+R&rft.aulast=Stern&rft.aufirst=MD&rft.date=2003-04-01&rft.volume=19&rft.issue=4&rft.spage=443&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 ER - TY - JOUR T1 - Dual activation of PPARalpha and PPARgamma by mono-(2-ethylhexyl) phthalate in rat ovarian granulosa cells. AN - 73202451; 12706301 AB - Peroxisome proliferator-activated receptors (PPARs) are key regulators of lipid metabolism and cell differentiation. The plasticizer di-(2-ethylhexyl) phthalate is a peroxisome proliferator, and its active metabolite mono-(2-ethylhexyl) phthalate (MEHP) activates PPARalpha and PPARgamma in cell transactivation assays. MEHP is a female reproductive toxicant and decreases activity, mRNA, and protein levels of aromatase, the rate-limiting enzyme that converts testosterone to estradiol in ovarian granulosa cells. To test the hypothesis that MEHP suppresses aromatase through PPAR pathways, granulosa cells were cultured with MEHP (50 microM) or selective activators of PPARgamma or PPARalpha for 48 h and gene expression was analyzed by real time RT-PCR. Both PPARalpha and PPARgamma activators significantly decreased aromatase mRNA and estradiol production like MEHP. The PPARgamma-selective antagonist GR 259662 partially blocked the suppression of aromatase by MEHP, suggesting that MEHP acts through PPARgamma, but not exclusively. MEHP and the PPARalpha-selective agonist GW 327647 induced expression of 17beta-hydroxysteroid dehydrogenase IV, a known PPARalpha-regulated gene, and induction was maintained with addition of the PPARgamma-selective antagonist. PPARalpha-selective activation also induced expression of aryl hydrocarbon receptor (AhR), CYP1B1, and epoxide hydrolase in the granulosa cell. These data support a model in which MEHP activates both PPARalpha and PPARgamma to suppress aromatase and alter other genes related to metabolism and differentiation in the granulosa cell. JF - Molecular and cellular endocrinology AU - Lovekamp-Swan, Tara AU - Jetten, Anton M AU - Davis, Barbara J AD - Laboratory of Women's Health, National Institute of Environmental Health Sciences, P.O. Box 12233, MD A2-01, Research Triangle Park, NC 27709, USA. Y1 - 2003/03/28/ PY - 2003 DA - 2003 Mar 28 SP - 133 EP - 141 VL - 201 IS - 1-2 SN - 0303-7207, 0303-7207 KW - Aromatase Inhibitors KW - 0 KW - DNA-Binding Proteins KW - Enzyme Inhibitors KW - Multienzyme Complexes KW - Peroxisome Proliferators KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - Receptors, Cytoplasmic and Nuclear KW - Receptors, Retinoic Acid KW - Retinoid X Receptors KW - Transcription Factors KW - Estradiol KW - 4TI98Z838E KW - Diethylhexyl Phthalate KW - C42K0PH13C KW - 17-Hydroxysteroid Dehydrogenases KW - EC 1.1.- KW - Hsd17b4 protein, rat KW - EC 1.1.1.119 KW - Aromatase KW - EC 1.14.14.1 KW - Aryl Hydrocarbon Hydroxylases KW - Cyp1b1 protein, rat KW - Cytochrome P-450 CYP1B1 KW - Peroxisomal Multifunctional Protein-2 KW - EC 4.2.1.107 KW - Enoyl-CoA Hydratase KW - EC 4.2.1.17 KW - mono-(2-ethylhexyl)phthalate KW - FU2EWB60RT KW - Index Medicus KW - Receptors, Retinoic Acid -- metabolism KW - Animals KW - 17-Hydroxysteroid Dehydrogenases -- metabolism KW - Peroxisome Proliferators -- pharmacology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Radioimmunoassay KW - Estradiol -- metabolism KW - Rats KW - Rats, Inbred F344 KW - Aryl Hydrocarbon Hydroxylases -- metabolism KW - Blotting, Western KW - Cells, Cultured KW - Aromatase -- genetics KW - Enzyme Inhibitors -- pharmacology KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Up-Regulation KW - Female KW - DNA-Binding Proteins -- metabolism KW - Granulosa Cells -- drug effects KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - RNA, Messenger -- analysis KW - Diethylhexyl Phthalate -- analogs & derivatives KW - Diethylhexyl Phthalate -- pharmacology KW - Granulosa Cells -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73202451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+endocrinology&rft.atitle=Dual+activation+of+PPARalpha+and+PPARgamma+by+mono-%282-ethylhexyl%29+phthalate+in+rat+ovarian+granulosa+cells.&rft.au=Lovekamp-Swan%2C+Tara%3BJetten%2C+Anton+M%3BDavis%2C+Barbara+J&rft.aulast=Lovekamp-Swan&rft.aufirst=Tara&rft.date=2003-03-28&rft.volume=201&rft.issue=1-2&rft.spage=133&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+endocrinology&rft.issn=03037207&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-29 N1 - Date created - 2003-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell cycle modulation of gene targeting by a triple helix-forming oligonucleotide. AN - 73120911; 12538585 AB - Successful gene-targeting reagents must be functional under physiological conditions and must bind chromosomal target sequences embedded in chromatin. Triple helix-forming oligonucleotides (TFOs) recognize and bind specific sequences via the major groove of duplex DNA and may have potential for gene targeting in vivo. We have constructed chemically modified, psoralen-linked TFOs that mediate site-specific mutagenesis of a chromosomal gene in living cells. Here we show that targeting efficiency is sensitive to the biology of the cell, specifically, cell cycle status. Targeted mutagenesis was variable across the cycle with the greatest activity in S phase. This was the result of differential TFO binding as measured by cross-link formation. Targeted cross-linking was low in quiescent cells but substantially enhanced in S phase cells with adducts in approximately 20-30% of target sequences. 75-80% of adducts were repaired faithfully, whereas the remaining adducts were converted into mutations (>5% mutation frequency). Clones with mutations could be recovered by direct screening of colonies chosen at random. These results demonstrate high frequency target binding and target mutagenesis by TFOs in living cells. Successful protocols for TFO-mediated manipulation of chromosomal sequences are likely to reflect a combination of appropriate oligonucleotide chemistry and manipulation of the cell biology. JF - The Journal of biological chemistry AU - Majumdar, Alokes AU - Puri, Nitin AU - Cuenoud, Bernard AU - Natt, Francois AU - Martin, Pierre AU - Khorlin, Alexander AU - Dyatkina, Natalia AU - George, Albert J AU - Miller, Paul S AU - Seidman, Michael M AD - Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2003/03/28/ PY - 2003 DA - 2003 Mar 28 SP - 11072 EP - 11077 VL - 278 IS - 13 SN - 0021-9258, 0021-9258 KW - triplex DNA KW - 0 KW - DNA KW - 9007-49-2 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - Index Medicus KW - Animals KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - CHO Cells KW - Cricetinae KW - DNA -- physiology KW - Gene Targeting KW - Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73120911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cell+cycle+modulation+of+gene+targeting+by+a+triple+helix-forming+oligonucleotide.&rft.au=Majumdar%2C+Alokes%3BPuri%2C+Nitin%3BCuenoud%2C+Bernard%3BNatt%2C+Francois%3BMartin%2C+Pierre%3BKhorlin%2C+Alexander%3BDyatkina%2C+Natalia%3BGeorge%2C+Albert+J%3BMiller%2C+Paul+S%3BSeidman%2C+Michael+M&rft.aulast=Majumdar&rft.aufirst=Alokes&rft.date=2003-03-28&rft.volume=278&rft.issue=13&rft.spage=11072&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 - 2003-05-02 N1 - Date created - 2003-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TRPC1 is required for functional store-operated Ca2+ channels. Role of acidic amino acid residues in the S5-S6 region. AN - 73111549; 12536150 AB - The exact role of TRPC1 in store-operated calcium influx channel (SOCC) function is not known. We have examined the effect of overexpression of full-length TRPC1, depletion of endogenous TRPC1, and expression of TRPC1 in which the proposed pore region (S5-S6, amino acids (aa) 557-620) was deleted or modified by site-directed mutagenesis on thapsigargin- and carbachol-stimulated SOCC activity in HSG cells. TRPC1 overexpression induced channel activity that was indistinguishable from the endogenous SOCC activity. Transfection with antisense hTRPC1 decreased SOCC activity although characteristics of SOCC-mediated current, I(SOC), were not altered. Expression of TRPC1 Delta 567-793, but not TRPC1 Delta 664-793, induced a similar decrease in SOCC activity. Furthermore, TRPC1 Delta 567-793 was co-immunoprecipitated with endogenous TRPC1. Simultaneous substitutions of seven acidic aa in the S5-S6 region (Asp --> Asn and Glu --> Gln) decreased SOCC-mediated Ca(2+), but not Na(+), current and induced a left shift in E(rev). Similar effects were induced by E576K or D581K, but not D581N or E615K, substitution. Furthermore, expressed TRPC1 proteins interacted with each other. Together, these data demonstrate that TRPC1 is required for generation of functional SOCC in HSG cells. We suggest that TRPC1 monomers co-assemble to form SOCC and that specific acidic aa residues in the proposed pore region of TRPC1 contribute to Ca(2+) influx. JF - The Journal of biological chemistry AU - Liu, Xibao AU - Singh, Brij B AU - Ambudkar, Indu S AD - Secretory Physiology Section, Gene Therapy and Therapeutics Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/03/28/ PY - 2003 DA - 2003 Mar 28 SP - 11337 EP - 11343 VL - 278 IS - 13 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - Calcium Channels KW - TRPC Cation Channels KW - transient receptor potential cation channel, subfamily C, member 1 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Cells, Cultured KW - Hydrogen-Ion Concentration KW - Molecular Sequence Data KW - Membrane Potentials -- physiology KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Precipitin Tests KW - Calcium Channels -- physiology KW - Calcium Channels -- chemistry KW - Calcium Channels -- genetics KW - Amino Acids -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73111549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=TRPC1+is+required+for+functional+store-operated+Ca2%2B+channels.+Role+of+acidic+amino+acid+residues+in+the+S5-S6+region.&rft.au=Liu%2C+Xibao%3BSingh%2C+Brij+B%3BAmbudkar%2C+Indu+S&rft.aulast=Liu&rft.aufirst=Xibao&rft.date=2003-03-28&rft.volume=278&rft.issue=13&rft.spage=11337&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 - 2003-05-02 N1 - Date created - 2003-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence for phosphorylation requirement for human bilirubin UDP-glucuronosyltransferase (UGT1A1) activity. AN - 73103451; 12646172 AB - Our discovery of rapid down-regulation of human bilirubin UDP-glucuronosyltransferase (UGT) in colon cell lines that was transient and irreversible following curcumin- and calphostin-C-treatment, respectively, suggested phosphorylation event(s) were involved in activity. Likewise, bilirubin-UGT1A1 expressed in COS-1 cells was inhibited by curcumin and calphostin-C. Because calphostin-C is a highly specific protein kinase C (PKC) inhibitor, we examined and found 4 to 5 predicted PKC phosphorylation sites in 11 UGTs examined. UGT1A1 incorporated [33P]orthophosphate, which was inhibited by calphostin-C. Also triple mutant, T75A/T112A/S435G-UGT1A1, at predicted PKC sites failed to incorporate [33P]orthophosphate. Individual or double mutants exhibited dominant-negative, additive, or no effect, while the triple mutant retained 10-15% activity towards bilirubin and two xenobiotics. Compared to wild-type, S435G and T112A/S435G shifted pH-optimum for eugenol, but not for bilirubin or anthraflavic acid, toward alkaline and acid conditions, respectively. This represents the first evidence that a UGT isozyme requires phosphorylation for activity. JF - Biochemical and biophysical research communications AU - Basu, Nikhil K AU - Kole, Labanyamoy AU - Owens, Ida S AD - Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1830, USA. Y1 - 2003/03/28/ PY - 2003 DA - 2003 Mar 28 SP - 98 EP - 104 VL - 303 IS - 1 SN - 0006-291X, 0006-291X KW - Enzyme Inhibitors KW - 0 KW - Naphthalenes KW - Recombinant Proteins KW - UGT1A1 enzyme KW - EC 2.4.1.- KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Glucuronidase KW - EC 3.2.1.31 KW - calphostin C KW - I271P23G24 KW - Curcumin KW - IT942ZTH98 KW - Bilirubin KW - RFM9X3LJ49 KW - Index Medicus KW - Animals KW - COS Cells KW - Dose-Response Relationship, Drug KW - Hydrogen-Ion Concentration KW - Humans KW - Glucuronidase -- metabolism KW - Amino Acid Sequence KW - Binding Sites KW - Curcumin -- pharmacology KW - Protein Kinase C -- metabolism KW - Mutagenesis, Site-Directed KW - Naphthalenes -- metabolism KW - Protein Kinase C -- antagonists & inhibitors KW - Blotting, Western KW - Curcumin -- metabolism KW - Tumor Cells, Cultured KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - Bilirubin -- metabolism KW - Molecular Sequence Data KW - Enzyme Inhibitors -- pharmacology KW - Sequence Homology, Amino Acid KW - Time Factors KW - Catalysis KW - Glucuronosyltransferase -- metabolism KW - Glucuronosyltransferase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73103451?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+for+phosphorylation+requirement+for+human+bilirubin+UDP-glucuronosyltransferase+%28UGT1A1%29+activity.&rft.au=Basu%2C+Nikhil+K%3BKole%2C+Labanyamoy%3BOwens%2C+Ida+S&rft.aulast=Basu&rft.aufirst=Nikhil&rft.date=2003-03-28&rft.volume=303&rft.issue=1&rft.spage=98&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 - 2003-05-22 N1 - Date created - 2003-03-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Muscarinic receptor subtypes mediating central and peripheral antinociception studied with muscarinic receptor knockout mice: a review. AN - 73080795; 12628455 AB - To gain new insight into the physiological and pathophysiological roles of the muscarinic cholinergic system, we generated mutant mouse strains deficient in each of the five muscarinic acetylcholine receptor subtypes (M(1)-M(5)). In this chapter, we review a set of recent studies dealing with the identification of the muscarinic receptor subtypes mediating muscarinic agonist-dependent analgesic effects by central and peripheral mechanisms. Most of these studies were carried out with mutant mouse strains lacking M(2) or/and M(4) muscarinic receptors. It is well known that administration of centrally active muscarinic agonists induces pronounced analgesic effects. To identify the muscarinic receptors mediating this activity, wild-type and muscarinic receptor mutant mice were injected with the non-subtype-selective muscarinic agonist, oxotremorine (s.c., i.t., and i.c.v.), and analgesic effects were assessed in the tail-flick and hot-plate tests. These studies showed that M(2) receptors play a key role in mediating the analgesic effects of oxotremorine, both at the spinal and supraspinal level. However, studies with M(2)/M(4) receptor double KO mice indicated that M(4) receptors also contribute to this activity. Recent evidence suggests that activation of muscarinic receptors located in the skin can reduce the sensitivity of peripheral nociceptors. Electrophysiological and neurochemical studies with skin preparations from muscarinic receptor mutant mice indicated that muscarine-induced peripheral antinociception is mediated by M(2) receptors. Since acetylcholine is synthesized and released by different cell types of the skin, it is possible that non-neuronally released acetylcholine plays a role in modulating peripheral nociception. Our results highlight the usefulness of muscarinic receptor mutant mice to shed light on the functional roles of acetylcholine released from both neuronal and non-neuronal cells. JF - Life sciences AU - Wess, Jürgen AU - Duttaroy, Alokesh AU - Gomeza, Jesus AU - Zhang, Weilie AU - Yamada, Masahisa AU - Felder, Christian C AU - Bernardini, Nadia AU - Reeh, Peter W AD - Laboratory of Bioorganic Chemistry, Molecular Signaling Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bldg 8A, Room B1A-05, 8 Center Drive MSC 0810, Bethesda, MD 20892-0810, USA. jwess@helix.nih.gov Y1 - 2003/03/28/ PY - 2003 DA - 2003 Mar 28 SP - 2047 EP - 2054 VL - 72 IS - 18-19 SN - 0024-3205, 0024-3205 KW - Analgesics KW - 0 KW - Receptors, Muscarinic KW - Calcitonin Gene-Related Peptide KW - 83652-28-2 KW - Index Medicus KW - Animals KW - Spinal Cord -- metabolism KW - Skin -- metabolism KW - Spinal Cord -- drug effects KW - Skin -- innervation KW - Mice KW - Nerve Endings -- drug effects KW - Mice, Knockout KW - Calcitonin Gene-Related Peptide -- metabolism KW - Receptors, Muscarinic -- genetics KW - Pain -- drug therapy KW - Pain -- physiopathology KW - Central Nervous System -- physiopathology KW - Central Nervous System -- drug effects KW - Analgesics -- pharmacology KW - Receptors, Muscarinic -- drug effects KW - Peripheral Nervous System -- drug effects KW - Receptors, Muscarinic -- physiology KW - Analgesics -- adverse effects KW - Peripheral Nervous System -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73080795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+sciences&rft.atitle=Muscarinic+receptor+subtypes+mediating+central+and+peripheral+antinociception+studied+with+muscarinic+receptor+knockout+mice%3A+a+review.&rft.au=Wess%2C+J%C3%BCrgen%3BDuttaroy%2C+Alokesh%3BGomeza%2C+Jesus%3BZhang%2C+Weilie%3BYamada%2C+Masahisa%3BFelder%2C+Christian+C%3BBernardini%2C+Nadia%3BReeh%2C+Peter+W&rft.aulast=Wess&rft.aufirst=J%C3%BCrgen&rft.date=2003-03-28&rft.volume=72&rft.issue=18-19&rft.spage=2047&rft.isbn=&rft.btitle=&rft.title=Life+sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-04 N1 - Date created - 2003-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of current DSM-IV alcohol use disorders in short-stay, general hospital admissions, United States, 1994. AN - 73113006; 12639205 AB - This study provides, to our knowledge, the first national prevalence estimates of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), alcohol use disorders based on a structured, diagnostic instrument for inpatient admissions to US general hospitals. Existing prevalence estimates for inpatient admissions came from studies conducted in 1 or 2 hospitals and therefore do not support national inference. A multistage probability sample was designed to represent acute care admissions to nonfederal, short-stay, general hospitals in the contiguous United States; 2040 admissions (1613 males and 427 females) in 90 hospitals participated. An estimated 1.8 million (95% confidence interval, 1.3-2.2 million) annual hospital admissions met the criteria for a current (ie, in the past 12 months) DSM-IV alcohol use disorder. Overall prevalence was estimated to be 7.4% (95% confidence interval, 5.6%-9.1%). Among current-drinking admissions, estimated prevalence was 24.0% (95% confidence interval, 18.7%-29.4%), and males and females had similar rates. Pairwise comparisons showed significant elevations in the prevalence of alcohol use disorders in current-drinking admissions who were younger, black, unmarried, of a lower socioeconomic status, on Medicaid or without health insurance, smokers, or drug users. Prevalence of alcohol use disorders was also significantly higher in current-drinking admissions in hospitals that were government owned, had medical school affiliations, or had a high number of emergency department visits per day. The prevalence of alcohol abuse or dependence in current-drinking admissions was substantial, suggesting that hospitalization offers a unique opportunity to identify alcohol use disorders. Further research is needed to determine factors that may be associated with significant pairwise results, especially for race or ethnicity. We recommend alcohol screening of all hospitalized drinkers, followed, as appropriate, by diagnostic evaluation and referral or intervention. JF - Archives of internal medicine AU - Smothers, Barbara A AU - Yahr, Harold T AU - Sinclair, Michael D AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-7003, USA. bs86h@nih.gov Y1 - 2003/03/24/ PY - 2003 DA - 2003 Mar 24 SP - 713 EP - 719 VL - 163 IS - 6 SN - 0003-9926, 0003-9926 KW - Abridged Index Medicus KW - Index Medicus KW - Length of Stay KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Hospitals, General KW - United States -- epidemiology KW - Male KW - Female KW - Prevalence KW - Alcohol-Related Disorders -- diagnosis KW - Patient Admission KW - Alcohol-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73113006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+internal+medicine&rft.atitle=Prevalence+of+current+DSM-IV+alcohol+use+disorders+in+short-stay%2C+general+hospital+admissions%2C+United+States%2C+1994.&rft.au=Smothers%2C+Barbara+A%3BYahr%2C+Harold+T%3BSinclair%2C+Michael+D&rft.aulast=Smothers&rft.aufirst=Barbara&rft.date=2003-03-24&rft.volume=163&rft.issue=6&rft.spage=713&rft.isbn=&rft.btitle=&rft.title=Archives+of+internal+medicine&rft.issn=00039926&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-02 N1 - Date created - 2003-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence context at human single nucleotide polymorphisms: overrepresentation of CpG dinucleotide at polymorphic sites and suppression of variation in CpG islands. AN - 73079792; 12628237 AB - Human polymorphisms originate as mutations, and the influence of context on mutagenesis should be reflected in the distribution of sequences surrounding single nucleotide polymorphisms (SNPs). We have performed a computational survey of nearly two million human SNPs to determine if sequence-dependent hotspots for polymorphism exist in the human genome. Here we show that sequences containing CpG dinucleotides, which occur at low frequencies in the human genome, are 6.7-fold more abundant at polymorphic sites than expected. In contrast, polymorphisms in CpG sequences located within CpG islands, important regulatory regions that modulate gene expression, are 6.8-fold less prevalent than expected. The distribution of polymorphic alleles at CpGs in CpG islands is also significantly different from that in non-island regions. These data strongly support a role for 5-methylcytosine deamination in the generation of human variation, and suggest that variation at CpGs in islands is suppressed. JF - Journal of molecular biology AU - Tomso, Daniel J AU - Bell, Douglas A AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, C3-03 P.O. Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2003/03/21/ PY - 2003 DA - 2003 Mar 21 SP - 303 EP - 308 VL - 327 IS - 2 SN - 0022-2836, 0022-2836 KW - DNA Primers KW - 0 KW - 5-Methylcytosine KW - 6R795CQT4H KW - Cytosine KW - 8J337D1HZY KW - Index Medicus KW - Genetic Variation KW - Alleles KW - Gene Frequency KW - DNA Methylation KW - Polymorphism, Genetic KW - Humans KW - Deamination KW - Databases, Factual KW - Chromosomes -- genetics KW - DNA Primers -- chemistry KW - Genome, Human KW - Dinucleotide Repeats -- genetics KW - Cytosine -- pharmacology KW - CpG Islands -- genetics KW - Polymorphism, Single Nucleotide -- genetics KW - Cytosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73079792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Sequence+context+at+human+single+nucleotide+polymorphisms%3A+overrepresentation+of+CpG+dinucleotide+at+polymorphic+sites+and+suppression+of+variation+in+CpG+islands.&rft.au=Tomso%2C+Daniel+J%3BBell%2C+Douglas+A&rft.aulast=Tomso&rft.aufirst=Daniel&rft.date=2003-03-21&rft.volume=327&rft.issue=2&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-24 N1 - Date created - 2003-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic alterations in cancer as a result of breakage at fragile sites. AN - 73101278; 12637148 AB - The organization and replication of DNA render fragile sites (FSs) prone to breakage, recombination as well as becoming preferential targets for mutagens-carcinogens and integration of oncogenic viruses. For many years, attempts to link FSs and cancer generated mostly circumstantial evidence. The discoveries that chromosome translocations, amplification of proto-oncogenes, deletion of tumor suppressor genes, and integration of oncogenic viruses all result from the specific breakage of genomic DNA at FSs, however, have provided compelling support for such a link, further suggesting a causative role for FSs in cancer. JF - Cancer letters AU - Popescu, Nicholas C AD - Molecular Cytogenetics Section, Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20814-4958, USA. popescum@dc37a.nci.nih.gov Y1 - 2003/03/20/ PY - 2003 DA - 2003 Mar 20 SP - 1 EP - 17 VL - 192 IS - 1 SN - 0304-3835, 0304-3835 KW - Carcinogens KW - 0 KW - Mutagens KW - Index Medicus KW - Translocation, Genetic -- genetics KW - Carcinogens -- pharmacology KW - Recombination, Genetic -- drug effects KW - Recombination, Genetic -- genetics KW - Humans KW - Chromosome Fragile Sites KW - Mutagens -- pharmacology KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Gene Expression Regulation, Neoplastic -- genetics KW - Neoplasms -- virology KW - Chromosome Fragility -- genetics KW - Neoplasms -- chemically induced KW - Neoplasms -- genetics KW - Neoplasms -- etiology KW - Chromosome Breakage -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73101278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+alterations+in+cancer+as+a+result+of+breakage+at+fragile+sites.&rft.au=Popescu%2C+Nicholas+C&rft.aulast=Popescu&rft.aufirst=Nicholas&rft.date=2003-03-20&rft.volume=192&rft.issue=1&rft.spage=1&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 - 2003-05-30 N1 - Date created - 2003-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - UV-C-induced DNA damage leads to p53-dependent nuclear trafficking of PML. AN - 73096424; 12642865 AB - The promyelocytic leukemia protein (PML) is a nuclear phosphoprotein that localizes to distinct domains in the nucleus, described as PML nuclear bodies (PML-NBs). Recent findings indicate that PML regulates the p53 response to oncogenic signals. Here, we define a p53-dependent role for PML in response to DNA damage. We exposed cells to ultraviolet light (UV-C) and imaged the nuclear distribution of PML, p53, and the BLM helicase by confocal microscopy. After DNA damage, PML partially relocated out of the PML-NBs, and colocalized with BLM and p53 at sites of DNA repair. In addition, using the isogenic HCT116 cell lines (p53+/+ and -/-), we show that the redistribution of PML was dependent on functional p53. Western analysis revealed that the level of PML protein remained unaltered after UV-C treatment. These results are consistent with the hypothesis that PML, in conjunction with p53 and BLM, contributes to the cellular response to UV-C-induced DNA damage and its repair. JF - Oncogene AU - Seker, Hasan AU - Rubbi, Carlos AU - Linke, Steven P AU - Bowman, Elise D AU - Garfield, Susan AU - Hansen, Laura AU - Borden, Katherine L B AU - Milner, Jo AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, CCR, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. Y1 - 2003/03/20/ PY - 2003 DA - 2003 Mar 20 SP - 1620 EP - 1628 VL - 22 IS - 11 SN - 0950-9232, 0950-9232 KW - Neoplasm Proteins KW - 0 KW - Nuclear Proteins KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - Tumor Suppressor Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Microscopy, Confocal KW - Reverse Transcriptase Polymerase Chain Reaction KW - Cell Line KW - Ultraviolet Rays KW - Tumor Suppressor Protein p53 -- physiology KW - Transcription Factors -- metabolism KW - DNA Damage KW - DNA -- radiation effects KW - Neoplasm Proteins -- metabolism KW - Protein Transport -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73096424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=UV-C-induced+DNA+damage+leads+to+p53-dependent+nuclear+trafficking+of+PML.&rft.au=Seker%2C+Hasan%3BRubbi%2C+Carlos%3BLinke%2C+Steven+P%3BBowman%2C+Elise+D%3BGarfield%2C+Susan%3BHansen%2C+Laura%3BBorden%2C+Katherine+L+B%3BMilner%2C+Jo%3BHarris%2C+Curtis+C&rft.aulast=Seker&rft.aufirst=Hasan&rft.date=2003-03-20&rft.volume=22&rft.issue=11&rft.spage=1620&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-22 N1 - Date created - 2003-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Troglitazone but not rosiglitazone induces G1 cell cycle arrest and apoptosis in human and rat hepatoma cell lines. AN - 73027078; 12595159 AB - Rosiglitazone (RSG), an agonist of peroxisome proliferator-activated receptor gamma (PPARgamma), induces minor toxicity in humans relative to another PPARgamma agonist, troglitazone (TRO). In contrast, recent reports suggest that RSG causes growth arrest and apoptosis of normal and cancerous cells. Therefore, in this study, we investigated the relative toxicities of TRO and RSG on three different hepatoma cell lines, and observed that TRO, but not RSG, was cytotoxic. Additionally, we studied the mechanism by which TRO induced damage to HepG2 hepatoma cells. Our results indicated that TRO increased the levels of p53, p27, and p21, while it reduced the levels of cyclin D1 and phospho-Rb in a time-dependent manner. Increased p27 and p21 levels coincided with reduced activities of cell cycle dependent kinases (cdk) such as cdk2- and cyclin A-protein kinases 24 h after TRO treatment. These results demonstrate that TRO, but not RSG, causes G1 arrest of hepatoma cells, most likely through changing the levels of cell cycle regulators. Furthermore, because RSG did not affect the levels of cell cycle regulators, TRO-mediated growth inhibition appears independent of PPARgamma activation. JF - Toxicology letters AU - Bae, Myung-Ae AU - Rhee, Herman AU - Song, Byoung J AD - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, NIH, 12420 Parklawn Drive, Rockville, MD 20852, USA. Y1 - 2003/03/20/ PY - 2003 DA - 2003 Mar 20 SP - 67 EP - 75 VL - 139 IS - 1 SN - 0378-4274, 0378-4274 KW - Antineoplastic Agents KW - 0 KW - CDKN1A protein, human KW - Cdkn1a protein, rat KW - Cdkn1b protein, rat KW - Cell Cycle Proteins KW - Chromans KW - Cyclin A KW - Cyclin E KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Thiazoles KW - Thiazolidinediones KW - Tumor Suppressor Protein p53 KW - Tumor Suppressor Proteins KW - rosiglitazone KW - 05V02F2KDG KW - Cyclin D1 KW - 136601-57-5 KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDC2-CDC28 Kinases KW - EC 2.7.11.22 KW - CDK2 protein, human KW - Cdk2 protein, rat KW - Cyclin-Dependent Kinase 2 KW - Cyclin-Dependent Kinases KW - troglitazone KW - I66ZZ0ZN0E KW - Index Medicus KW - Cyclin A -- metabolism KW - Cyclin-Dependent Kinases -- metabolism KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - Humans KW - Tumor Suppressor Protein p53 -- metabolism KW - Cell Cycle Proteins -- metabolism KW - Rats KW - Cyclin E -- metabolism KW - Cyclin D1 -- metabolism KW - Tumor Cells, Cultured KW - Tumor Suppressor Proteins -- metabolism KW - Cyclins -- metabolism KW - Thiazoles -- pharmacology KW - Liver Neoplasms -- pathology KW - Chromans -- pharmacology KW - Apoptosis -- drug effects KW - G1 Phase -- drug effects KW - Antineoplastic Agents -- pharmacology KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73027078?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+letters&rft.atitle=Troglitazone+but+not+rosiglitazone+induces+G1+cell+cycle+arrest+and+apoptosis+in+human+and+rat+hepatoma+cell+lines.&rft.au=Bae%2C+Myung-Ae%3BRhee%2C+Herman%3BSong%2C+Byoung+J&rft.aulast=Bae&rft.aufirst=Myung-Ae&rft.date=2003-03-20&rft.volume=139&rft.issue=1&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Toxicology+letters&rft.issn=03784274&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-16 N1 - Date created - 2003-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term correction of globotriaosylceramide storage in Fabry mice by recombinant adeno-associated virus-mediated gene transfer AN - 18703728; 5588323 AB - Fabry disease is an X-linked recessive inborn metabolic disorder characterized by systemic and vascular accumulation of globotriaosylceramide (Gb sub(3)) caused by a deficiency of the lysosomal enzyme alpha -galactosidase A ( alpha -gal A). The condition is associated with an increased morbidity and mortality due to renal failure, cardiac disease, and early onset of stroke. Hemizygous males are primarily affected clinically with variable expression in heterozygous females. Gene-therapy trials have been initiated recently in alpha -gal A knockout mouse models of Fabry disease by using a variety of viral vectors. In the present investigation we administered single i.v. injections of 1 x 10 super(10) genomes of recombinant adeno-associated virus (rAAV) encoding the human alpha -gal A gene driven by a modified chicken beta -actin (CAG) promoter to alpha -gal A knockout (Fabry) mice. Transgenic mice were analyzed for expression of alpha -gal A activity and Gb sub(3) levels in liver, kidney, heart, spleen, small intestine, lung, and brain. Administration of the rAAV-CAG-hAGA vector resulted in stable expression of alpha -gal A in organs of the Fabry mice for >6 months. alpha -Gal A activity in the organs became equal to or higher than that of wild-type mice. Accumulated Gb sub(3) in the liver, heart, and spleen was reduced to that of wild-type mice with lesser but significant reductions in kidney, lung, and small intestine. Injection of the rAAV-CAG-hAGA construct into skeletal muscle did not result in expression of alpha -gal A in it or in other tissues. This study provides a basis for a simple and efficient gene-therapy approach for patients with Fabry disease and is indicative of its potential for the treatment of other lysosomal storage disorders. JF - Proceedings of the National Academy of Sciences, USA AU - Park, J AU - Murray, G J AU - Limaye, A AU - Quirk, J M AU - Gelderman, M P AU - Brady, RO AU - Qasba, P AD - Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 3D04, 10 Center Drive, Bethesda, MD 20892, qasbap@nhlbi.nih.gov Y1 - 2003/03/18/ PY - 2003 DA - 2003 Mar 18 SP - 3450 EP - 3454 VL - 100 IS - 6 SN - 0027-8424, 0027-8424 KW - Transgenic mice KW - globotriaosylceramide KW - globotriaosylceramides KW - knockout mice KW - lysosomal storage diseases KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - G 07397:Rodentia (mice) KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18703728?accountid=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=Long-term+correction+of+globotriaosylceramide+storage+in+Fabry+mice+by+recombinant+adeno-associated+virus-mediated+gene+transfer&rft.au=Park%2C+J%3BMurray%2C+G+J%3BLimaye%2C+A%3BQuirk%2C+J+M%3BGelderman%2C+M+P%3BBrady%2C+RO%3BQasba%2C+P&rft.aulast=Park&rft.aufirst=J&rft.date=2003-03-18&rft.volume=100&rft.issue=6&rft.spage=3450&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.0537900100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1073/pnas.0537900100 ER - TY - JOUR T1 - [Treatment and prevention of hepatitis C--progress and challenges. The Danish Society of Hepatology]. TT - Behandling og forebyggelse af hepatitis C--fremskridt og udfordringer. Dansk Selskab for Hepatologi. AN - 73208769; 12701283 JF - Ugeskrift for laeger AU - Bukh, Jens AU - Christensen, Erik AU - Krogsgaard, Kim AD - jbukh@niaid.nih.gov Y1 - 2003/03/17/ PY - 2003 DA - 2003 Mar 17 SP - 1233 VL - 165 IS - 12 SN - 0041-5782, 0041-5782 KW - Antiviral Agents KW - 0 KW - Index Medicus KW - Antiviral Agents -- therapeutic use KW - Humans KW - Hepatitis C, Chronic -- prevention & control KW - Hepatitis C, Chronic -- drug therapy KW - Antiviral Agents -- adverse effects KW - Hepatitis C -- prevention & control KW - Hepatitis C -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73208769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ugeskrift+for+laeger&rft.atitle=%5BTreatment+and+prevention+of+hepatitis+C--progress+and+challenges.+The+Danish+Society+of+Hepatology%5D.&rft.au=Bukh%2C+Jens%3BChristensen%2C+Erik%3BKrogsgaard%2C+Kim&rft.aulast=Bukh&rft.aufirst=Jens&rft.date=2003-03-17&rft.volume=165&rft.issue=12&rft.spage=1233&rft.isbn=&rft.btitle=&rft.title=Ugeskrift+for+laeger&rft.issn=00415782&rft_id=info:doi/ LA - Danish DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-15 N1 - Date created - 2003-04-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Seroprevalence of human herpesvirus 8 among injection drug users in San Francisco. AN - 73145059; 12660944 AB - The association between injection drug use and human herpesvirus 8 (HHV-8) was examined to investigate bloodborne transmission of the virus. In all, 1905 injection drug users (IDUs) enrolled in a cross-sectional study were tested for K8.1 antibodies to HHV-8 lytic antigen. Logistic regression was used to adjust for demographic and sexual behavior variables. HHV-8 seroprevalence was 10% among women, 10% among heterosexual men, and 23% among men who have sex with men. In adjusted analyses, HHV-8 seroprevalence increased with longer duration of injection drug use for each of these groups (P = .01, P = .03, and P = .049 for trend, respectively). HHV-8 infection is relatively common among IDUs in San Francisco, and longer duration of injection drug use is associated with an increase in the risk of HHV-8 infection that is not explained by sexual behavior or demographic differences. These results are consistent with the occurrence of bloodborne transmission of HHV-8 among IDUs. JF - The Journal of infectious diseases AU - Atkinson, Jonnae AU - Edlin, Brian R AU - Engels, Eric A AU - Kral, Alex H AU - Seal, Karen AU - Gamache, Christine J AU - Whitby, Denise AU - O'Brien, Thomas R AD - Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20852, USA. Y1 - 2003/03/15/ PY - 2003 DA - 2003 Mar 15 SP - 974 EP - 981 VL - 187 IS - 6 SN - 0022-1899, 0022-1899 KW - Antibodies, Viral KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Seroepidemiologic Studies KW - Disease Transmission, Infectious KW - Multivariate Analysis KW - Sexuality KW - Antibodies, Viral -- blood KW - Demography KW - Cross-Sectional Studies KW - Risk Factors KW - Adult KW - Middle Aged KW - San Francisco -- epidemiology KW - Time Factors KW - Female KW - Male KW - Herpesviridae Infections -- transmission KW - Herpesvirus 8, Human -- immunology KW - Herpesviridae Infections -- epidemiology KW - Herpesviridae Infections -- etiology KW - Substance Abuse, Intravenous -- blood KW - Substance Abuse, Intravenous -- epidemiology KW - Substance Abuse, Intravenous -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73145059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Seroprevalence+of+human+herpesvirus+8+among+injection+drug+users+in+San+Francisco.&rft.au=Atkinson%2C+Jonnae%3BEdlin%2C+Brian+R%3BEngels%2C+Eric+A%3BKral%2C+Alex+H%3BSeal%2C+Karen%3BGamache%2C+Christine+J%3BWhitby%2C+Denise%3BO%27Brien%2C+Thomas+R&rft.aulast=Atkinson&rft.aufirst=Jonnae&rft.date=2003-03-15&rft.volume=187&rft.issue=6&rft.spage=974&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-25 N1 - Date created - 2003-03-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Infect Dis. 2003 Jul 1;188(1):175-6 [12825189] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlation between sonochemistry of surfactant solutions and human leukemia cell killing by ultrasound and porphyrins. AN - 73095540; 12633748 AB - The synergistic effect of ultrasound and drugs on cells is known as sonodynamic therapy. The use of sonodynamic therapy for the potential clinical treatment of certain tumors is promising, however, the mechanism of sonodynamic therapy could be due to either sonomechanical and/or sonochemical effects on the cells. The aim of the current study is to determine the importance of the sonochemical mechanism for sonodynamic therapy. Sonochemical effects arise from the formation of radical species following collapse of cavitation bubbles. The synergistic effect of ultrasound (47 kHz) and analogues of a gallium-porphyrin derivative (ATX-70) on cytolysis of Human leukemia cells (HL-525 and HL-60) suspended in a cell culture medium were studied. Organic surfactants preferentially accumulate and subsequently decompose at the gas/solution interface of cavitation bubbles, producing secondary radicals that can diffuse to the bulk solution. The gallium porphyrin analogues used in the current study possess two n-alkyl side chains (ATX-C(x), where x = number of carbon atoms, ranging from x = 2 to x = 12). By varying the n-alkyl chain length, thereby modifying the surfactant properties of the ATX-C(x) derivatives, cell killing in relation to the accumulation of ATX-C(x) derivatives at the gas/solution interface of cavitation bubbles was determined. Following sonolysis in the presence of ATX-C(x), a strong correlation for the yield of carbon-centered radicals and cell killing was observed. These results support the hypothesis that a sonochemical mechanism is responsible for the synergistic effect of ultrasound and ATX-C(x) on HL-525 and HL-60 cells. JF - Free radical biology & medicine AU - Miyoshi, Norio AU - Sostaric, Joe Z AU - Riesz, Peter AD - Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2003/03/15/ PY - 2003 DA - 2003 Mar 15 SP - 710 EP - 719 VL - 34 IS - 6 SN - 0891-5849, 0891-5849 KW - Free Radicals KW - 0 KW - Porphyrins KW - Surface-Active Agents KW - ATX 70 KW - 135099-39-7 KW - Gallium KW - CH46OC8YV4 KW - Index Medicus KW - Tumor Cells, Cultured KW - Combined Modality Therapy KW - Humans KW - Electron Spin Resonance Spectroscopy KW - Ultrasonic Therapy KW - Porphyrins -- toxicity KW - Leukemia -- therapy KW - Porphyrins -- chemistry KW - Cell Death -- radiation effects KW - Gallium -- chemistry KW - Gallium -- toxicity KW - Cell Death -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73095540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Correlation+between+sonochemistry+of+surfactant+solutions+and+human+leukemia+cell+killing+by+ultrasound+and+porphyrins.&rft.au=Miyoshi%2C+Norio%3BSostaric%2C+Joe+Z%3BRiesz%2C+Peter&rft.aulast=Miyoshi&rft.aufirst=Norio&rft.date=2003-03-15&rft.volume=34&rft.issue=6&rft.spage=710&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-07 N1 - Date created - 2003-03-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of serum-free medium on the expression of glutamate transporters and the susceptibility to glutamate toxicity in cultured cortical neurons. AN - 73051178; 12605407 AB - The presence of glia and glial glutamate transporters seems to modify glutamate-mediated toxicity in neuronal cultures. In this work we cultured cortical cells in serum-containing medium and in a serum-free medium (Neurobasal medium + B27 supplement) and studied the expression of the glutamate transporters GLAST, GLT, and EAAC by immunocytochemistry and RT-PCR. The proportion of glial cells was below 10% in the Neurobasal medium and 46% in the serum-containing medium. Semiquantitative evaluation of the mRNA for the glutamate transporters showed similar amounts in cells grown in serum-free and serum-containing media. We detected immunoreactivity for the three transporters in both media, but EAAC was coexpressed with the neuronal marker MAP2, whereas GLAST and GLT predominated in nonneuronal cells. When the cultures were treated with glutamate for 15 min, the cultures in serum-containing medium showed a clear concentration-dependent neuronal death, whereas cells primed in this medium and switched to Neurobasal medium, as well as cells grown only in the latter, were less sensitive to glutamate concentrations up to 1 mM. A similar difference in the sensitivity to excitotoxicity was observed when the glutamate uptake inhibitor L-trans-2,4-pyrrolidine-dicarboxylate was applied during 6 hr, although the accumulation of extracellular glutamate was similar in the two media. We conclude that glutamate transporters with the culture conditions studied are sensitive to glutamate uptake inhibition and that Neurobasal/B27 medium protects cells against excitotoxicity. Copyright 2003 Wiley-Liss, Inc. JF - Journal of neuroscience research AU - Velasco, Iván AU - Velasco-Velázquez, Marco A AU - Salazar, Patricia AU - Lajud, Naima AU - Tapia, Ricardo AD - Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F., México. velascoi@ninds.nih.gov Y1 - 2003/03/15/ PY - 2003 DA - 2003 Mar 15 SP - 811 EP - 818 VL - 71 IS - 6 SN - 0360-4012, 0360-4012 KW - Amino Acid Transport System X-AG KW - 0 KW - Culture Media, Serum-Free KW - RNA, Messenger KW - Glutamic Acid KW - 3KX376GY7L KW - Index Medicus KW - Rats KW - Cerebral Cortex -- cytology KW - Animals KW - Cerebral Cortex -- drug effects KW - Cerebral Cortex -- metabolism KW - Cells, Cultured KW - Astrocytes -- drug effects KW - RNA, Messenger -- analysis KW - Reverse Transcriptase Polymerase Chain Reaction KW - Cell Death -- drug effects KW - Immunohistochemistry KW - Astrocytes -- metabolism KW - Glutamic Acid -- toxicity KW - Neurons -- metabolism KW - Glutamic Acid -- metabolism KW - Amino Acid Transport System X-AG -- drug effects KW - Amino Acid Transport System X-AG -- biosynthesis KW - Culture Media, Serum-Free -- pharmacology KW - Culture Media, Serum-Free -- chemistry KW - Glutamic Acid -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73051178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Influence+of+serum-free+medium+on+the+expression+of+glutamate+transporters+and+the+susceptibility+to+glutamate+toxicity+in+cultured+cortical+neurons.&rft.au=Velasco%2C+Iv%C3%A1n%3BVelasco-Vel%C3%A1zquez%2C+Marco+A%3BSalazar%2C+Patricia%3BLajud%2C+Naima%3BTapia%2C+Ricardo&rft.aulast=Velasco&rft.aufirst=Iv%C3%A1n&rft.date=2003-03-15&rft.volume=71&rft.issue=6&rft.spage=811&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 - 2003-05-07 N1 - Date created - 2003-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prenatal Exposure to Low-Level Polychlorinated Biphenyls in Relation to Mental and Motor Development at 8 Months AN - 18775833; 5644747 AB - The relation between exposure to low levels of polychlorinated biphenyls (PCBs), a class of persistent organic pollutants, and cognitive and motor development in young children has been examined in several studies, and results have varied. The authors evaluated the association between prenatal exposure to PCBs and children's neurodevelopment using data from the Collaborative Perinatal Project. Pregnant women were enrolled from 1959 to 1965 from 12 sites across the United States. PCBs were measured in maternal serum taken during pregnancy. To measure children's mental and psychomotor development at 8 months of age, the authors administered the Bayley Scales of Infant Development (means, 87 (standard deviation, 15) and 88 (standard deviation, 18), respectively). Overall, they did not observe a relation between prenatal PCB exposure and children's mental or psychomotor scores (n = 1,207; multivariate adjusted beta = 0.1 point per mu g/liter increase of PCB, p = 0.71, and beta = 0.5, p = 0.14, respectively). The PCB-psychomotor score relation varied by study center (p < 0.05): The association was direct in some centers, inverse in others. This could not be attributed to variation in the timing or measurement of the child's neurodevelopment or analysis of PCBs because these were standardized across centers. The reasons for variation in results within this study and across other studies remain unclear. JF - American Journal of Epidemiology AU - Daniels, J L AU - Longnecker, M P AU - Klebanoff, MA AU - Gray, KA AU - Brock, J W AU - Zhou, H AU - Chen, Z AU - Needham, L L AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA Y1 - 2003/03/15/ PY - 2003 DA - 2003 Mar 15 SP - 485 EP - 492 VL - 157 IS - 6 SN - 0002-9262, 0002-9262 KW - cognitive ability KW - development KW - neurological complications KW - prenatal experience KW - Health & Safety Science Abstracts; Risk Abstracts; Pollution Abstracts KW - R2 23060:Medical and environmental health KW - H 12000:Epidemiology and Public Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18775833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Prenatal+Exposure+to+Low-Level+Polychlorinated+Biphenyls+in+Relation+to+Mental+and+Motor+Development+at+8+Months&rft.au=Daniels%2C+J+L%3BLongnecker%2C+M+P%3BKlebanoff%2C+MA%3BGray%2C+KA%3BBrock%2C+J+W%3BZhou%2C+H%3BChen%2C+Z%3BNeedham%2C+L+L&rft.aulast=Daniels&rft.aufirst=J&rft.date=2003-03-15&rft.volume=157&rft.issue=6&rft.spage=485&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Novel Uncomplexed and Complexed Structures of Plasmepsin II, an Aspartic Protease from Plasmodium falciparum AN - 18846841; 5613856 AB - Malaria remains a human disease of global significance and a major cause of high infant mortality in endemic nations. Parasites of the genus Plasmodium cause the disease by degrading human hemoglobin as a source of amino acids for their growth and maturation. Hemoglobin degradation is initiated by aspartic proteases, termed plasmepsins, with a cleavage at the alpha -chain between residues Phe33 and Leu34. Plasmepsin II is one of the four catalytically active plasmepsins that has been identified in the food vacuole of Plasmodium falciparum. Novel crystal structures of uncomplexed plasmepsin II as well as the complex with a potent inhibitor have been refined with data extending to resolution limits of 1.9A and 2.7A , and to R factors of 17% and 18%, respectively. The inhibitor, N-(3-{(2-benzo[1,3]dioxol-5-yl-ethyl)[3-(1-methyl-3-oxo-1,3-dih ydro-isoindol-2-yl)-propionyl]-amino}-1-benzyl-2-(hydroxypropyl)-4 -b enzyloxy-3,5-dimethoxy-benzamide, belongs to a family of potent non-peptidic inhibitors that have large P1 groups. Such inhibitors could not be modeled into the binding cavity of the structure of plasmepsin II in complex with pepstatin A. Our structures reveal that the binding cavities of the new complex and uncomplexed plasmepsin II are considerably more open than that of the pepstatin A complex, allowing for larger heterocyclic groups in the P1, P2 and P2 positions. Both complexed and uncomplexed plasmepsin II crystallized in space group P2, with one monomer in the asymmetric unit. The structures show extensive interlocking of monomers around the crystallographic axis of symmetry, with areas in excess of 2300A super(2) buried at the interface, and a loop of one monomer interacting with the binding cavity of the 2-fold related monomer. Electron density for this loop is only fully ordered in the complexed structure. JF - Journal of Molecular Biology AU - Asojo, O A AU - Gulnik, S V AU - Afonina, E AU - Yu, B AU - Ellman, JA AU - Haque, T S AU - Silva, A M AD - Structural Biochemistry Program, National Cancer Institute/SAIC, Frederick, MD 21702, USA, asojo@ncifcrf.gov Y1 - 2003/03/14/ PY - 2003 DA - 2003 Mar 14 SP - 173 EP - 181 PB - Elsevier Science Ltd VL - 327 IS - 1 SN - 0022-2836, 0022-2836 KW - Aspartic protease KW - hemoglobin KW - plasmepsin II KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality KW - Molecular structure KW - Mortality KW - Parasites KW - Protozoan diseases KW - Enzymes KW - Malaria KW - Plasmodium falciparum KW - Freshwater KW - Children KW - Chemical analysis KW - Haemoglobins KW - Q1 08206:Physiology, biochemistry, biophysics KW - K 03090:Protozoa: human KW - Q1 08484:Species interactions: parasites and diseases KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18846841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Novel+Uncomplexed+and+Complexed+Structures+of+Plasmepsin+II%2C+an+Aspartic+Protease+from+Plasmodium+falciparum&rft.au=Asojo%2C+O+A%3BGulnik%2C+S+V%3BAfonina%2C+E%3BYu%2C+B%3BEllman%2C+JA%3BHaque%2C+T+S%3BSilva%2C+A+M&rft.aulast=Asojo&rft.aufirst=O&rft.date=2003-03-14&rft.volume=327&rft.issue=1&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1016%2FS0022-2836%2803%2900036-6 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-07 N1 - SubjectsTermNotLitGenreText - Molecular structure; Parasites; Protozoan diseases; Enzymes; Malaria; Chemical analysis; Haemoglobins; Mortality; Children; Plasmodium falciparum; Freshwater DO - http://dx.doi.org/10.1016/S0022-2836(03)00036-6 ER - TY - JOUR T1 - Structure-based design of thioether-bridged cyclic phosphopeptides binding to Grb2-SH2 domain. AN - 73073151; 12617916 AB - A series of phosphotyrosine containing cyclic peptides was designed and synthesized based upon the phage library derived cyclopeptide, G1TE. Considering the type-I beta-turn feature of peptidic ligand binding to Grb2 SH2 domain, we introduce alpha,alpha-disubstituted cyclic amino acid, Ach, into the 4th position of the cyclic peptide to induce a local right handed 3(10) helical conformation. In order to stabilize the favorable binding conformation, the bulky and hydrophobic amino acids, neopentylglycine (NPG) and phenylalanine, were introduced into the 8th and 2nd positions of the peptide ligand, respectively. To facilitate the sidechain of pTyr3 reaching into the phosphotyrosine binding pocket, a less bulky alanine was preferred in position 1. Based upon these global modifications, a highly potent peptide ligand 12 was discovered with an IC(50)=1.68 nM, evaluated by ELISA binding essay. Ligand 12 is at least 10(5) more potent than the lead peptide, termed G1TE. JF - Bioorganic & medicinal chemistry letters AU - Li, Peng AU - Peach, Megan L AU - Zhang, Manchao AU - Liu, Hongpeng AU - Yang, Dajun AU - Nicklaus, Marc AU - Roller, Peter P AD - Laboratory of Medicinal Chemistry, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. Y1 - 2003/03/10/ PY - 2003 DA - 2003 Mar 10 SP - 895 EP - 899 VL - 13 IS - 5 SN - 0960-894X, 0960-894X KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Amino Acids KW - GRB2 Adaptor Protein KW - Peptides, Cyclic KW - Phosphopeptides KW - Proteins KW - Sulfides KW - Phosphotyrosine KW - 21820-51-9 KW - Index Medicus KW - Protein Structure, Secondary KW - Phosphotyrosine -- chemistry KW - Models, Molecular KW - Cyclization KW - Drug Design KW - Protein Binding KW - src Homology Domains KW - Structure-Activity Relationship KW - Binding Sites KW - Enzyme-Linked Immunosorbent Assay -- methods KW - Amino Acids -- chemistry KW - Inhibitory Concentration 50 KW - Molecular Conformation KW - Phosphopeptides -- metabolism KW - Proteins -- chemistry KW - Peptides, Cyclic -- metabolism KW - Sulfides -- chemistry KW - Peptides, Cyclic -- chemistry KW - Phosphopeptides -- chemistry KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73073151?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry+letters&rft.atitle=Structure-based+design+of+thioether-bridged+cyclic+phosphopeptides+binding+to+Grb2-SH2+domain.&rft.au=Li%2C+Peng%3BPeach%2C+Megan+L%3BZhang%2C+Manchao%3BLiu%2C+Hongpeng%3BYang%2C+Dajun%3BNicklaus%2C+Marc%3BRoller%2C+Peter+P&rft.aulast=Li&rft.aufirst=Peng&rft.date=2003-03-10&rft.volume=13&rft.issue=5&rft.spage=895&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry+letters&rft.issn=0960894X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-29 N1 - Date created - 2003-03-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional studies on native and mutated forms of perilipins. A role in protein kinase A-mediated lipolysis of triacylglycerols. AN - 73065967; 12477720 AB - Perilipin A coats the lipid storage droplets in adipocytes and is polyphosphorylated by protein kinase A (PKA); the fact that PKA activates lipolysis in adipocytes suggests a role for perilipins in this process. To assess whether perilipins participate directly in PKA-mediated lipolysis, we have expressed constructs coding for native and mutated forms of the two major splice variants of the perilipin gene, perilipins A and B, in Chinese hamster ovary fibroblasts. Perilipins localize to lipid droplet surfaces and displace the adipose differentiation-related protein that normally coats the droplets in these cells. Perilipin A inhibits triacylglycerol hydrolysis by 87% when PKA is quiescent, but activation of PKA and phosphorylation of perilipin A engenders a 7-fold lipolytic activation. Mutation of PKA sites within the N-terminal region of perilipin abrogates the PKA-mediated lipolytic response. In contrast, perilipin B exerts only minimal protection against lipolysis and is unresponsive to PKA activation. Since Chinese hamster ovary cells contain no PKA-activated lipase, we conclude that the expression of perilipin A alone is sufficient to confer PKA-mediated lipolysis in these cells. Moreover, the data indicate that the unique C-terminal portion of perilipin A is responsible for its protection against lipolysis and that phosphorylation at the N-terminal PKA sites attenuates this protective effect. JF - The Journal of biological chemistry AU - Tansey, John T AU - Huml, Anne M AU - Vogt, Rainbow AU - Davis, Kathryn E AU - Jones, Jennifer M AU - Fraser, Kathryn A AU - Brasaemle, Dawn L AU - Kimmel, Alan R AU - Londos, Constantine AD - Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-8028, USA. Y1 - 2003/03/07/ PY - 2003 DA - 2003 Mar 07 SP - 8401 EP - 8406 VL - 278 IS - 10 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - Perilipin-1 KW - Phosphoproteins KW - Triglycerides KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Animals KW - Phosphorylation KW - Cricetulus KW - Enzyme Activation KW - CHO Cells KW - Mice KW - Fluorescent Antibody Technique KW - Mutagenesis KW - Cricetinae KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Phosphoproteins -- genetics KW - Triglycerides -- metabolism KW - Phosphoproteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73065967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+studies+on+native+and+mutated+forms+of+perilipins.+A+role+in+protein+kinase+A-mediated+lipolysis+of+triacylglycerols.&rft.au=Tansey%2C+John+T%3BHuml%2C+Anne+M%3BVogt%2C+Rainbow%3BDavis%2C+Kathryn+E%3BJones%2C+Jennifer+M%3BFraser%2C+Kathryn+A%3BBrasaemle%2C+Dawn+L%3BKimmel%2C+Alan+R%3BLondos%2C+Constantine&rft.aulast=Tansey&rft.aufirst=John&rft.date=2003-03-07&rft.volume=278&rft.issue=10&rft.spage=8401&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 - 2003-04-23 N1 - Date created - 2003-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ribonuclease is partly responsible for the HIV-1 inhibitory effect activated by HLA alloantigen recognition. AN - 73039782; 12598767 AB - This study was performed to determine whether ribonucleases (RNases) contribute to the soluble HIV-1 inhibitory activity that results from the recognition of HLA alloantigens. Supernatants from mixed lymphocyte reactions of peripheral blood mononuclear cells from healthy HLA-discordant individuals exhibited HIV-1 inhibitory activity (alloantigen-stimulated factors; ASF). These supernatants were tested for their sensitivity to heating (90 degrees C for 3 min), and for the presence of three RNases belonging to the RNase A superfamily: eosinophil-derived neurotoxin (EDN); RNase A; and angiogenin. Polyclonal antibodies specific for these RNases were used for Western blot analysis of the ASF, as well as for blocking the HIV-1 inhibitory activity of ASF. In addition, an RNase inhibitor (RI) was used to determine whether the anti-viral activity of ASF was due to RNase activity. HIV-1 inhibitory activity of ASF was: (i). resistant to heat treatment; (ii). blocked by 58% with an antibody specific for EDN, but not with antibodies against RNase A or angiogenin; and (iii) blocked by 65-100% with an RI. Moreover, Western blot analysis with an anti-EDN antibody detected EDN in the ASF. These findings indicate that the majority of the soluble HIV-1 inhibitory activity contained in the supernatants of mixed lymphocyte reactions is due to EDN or a closely related RNase. JF - AIDS (London, England) AU - Rugeles, Maria T AU - Trubey, Charles M AU - Bedoya, Victoria I AU - Pinto, Ligia A AU - Oppenheim, Joost J AU - Rybak, Susanna M AU - Shearer, Gene M AD - Universidad de Antioquia, Medellin, Colombia, the Experimental Immunology Branch, NCI, NIH, Bethesda, USA. Y1 - 2003/03/07/ PY - 2003 DA - 2003 Mar 07 SP - 481 EP - 486 VL - 17 IS - 4 SN - 0269-9370, 0269-9370 KW - Antiviral Agents KW - 0 KW - Histocompatibility Antigens KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - AIDS/HIV KW - Lymphocyte Activation KW - Humans KW - Lymphocyte Culture Test, Mixed KW - Immunity, Innate KW - HIV Infections -- immunology KW - Histocompatibility Antigens -- immunology KW - Ribonucleases -- metabolism KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73039782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ribonuclease+is+partly+responsible+for+the+HIV-1+inhibitory+effect+activated+by+HLA+alloantigen+recognition.&rft.au=Rugeles%2C+Maria+T%3BTrubey%2C+Charles+M%3BBedoya%2C+Victoria+I%3BPinto%2C+Ligia+A%3BOppenheim%2C+Joost+J%3BRybak%2C+Susanna+M%3BShearer%2C+Gene+M&rft.aulast=Rugeles&rft.aufirst=Maria&rft.date=2003-03-07&rft.volume=17&rft.issue=4&rft.spage=481&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 - 2003-04-29 N1 - Date created - 2003-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of cardiac Ca(V)1.2 channels by dihydropyridine and phosphatase inhibitor requires Ser-1142 in the domain III pore loop. AN - 73077458; 12601159 AB - Dihydropyridine-sensitive, voltage-activated calcium channels respond to membrane depolarization with two distinct modes of activity: short bursts of very short openings (mode 1) or repetitive openings of much longer duration (mode 2). Here we show that both the dihydropyridine, BayK8644 (BayK), and the inhibitor of SerThr protein phosphatases, okadaic acid, have identical effects on the gating of the recombinant cardiac calcium channel, Ca(V)1.2 (alpha(1)C). Each produced identical mode 2 gating in cell-attached patches, and each prevented rundown of channel activity when the membrane patch was excised into ATP-free solutions. These effects required Ser or Thr at position 1142 in the domain III pore loop between transmembrane segments S5 and S6, where dihydropyridines bind to the channel. Mutation of Ser-1142 to Ala or Cys produced channels with very low activity that could not be modulated by either BayK or okadaic acid. A molecular model of Ca(V)1.2 indicates that Ser-1142 is unlikely to be phosphorylated, and thus we conclude that BayK binding stabilizes mode 2 gating allosterically by either protecting a phospho Ser/Thr on the alpha(1)C subunit or mimicking phosphorylation at that site. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Erxleben, Christian AU - Gomez-Alegria, Claudio AU - Darden, Thomas AU - Mori, Yasuo AU - Birnbaumer, Lutz AU - Armstrong, David L AD - Laboratory of Signal Transduction and Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA. Y1 - 2003/03/04/ PY - 2003 DA - 2003 Mar 04 SP - 2929 EP - 2934 VL - 100 IS - 5 SN - 0027-8424, 0027-8424 KW - Calcium Channel Agonists KW - 0 KW - Calcium Channels KW - Calcium Channels, L-Type KW - Dihydropyridines KW - Enzyme Inhibitors KW - L-type calcium channel alpha(1C) KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Threonine KW - 2ZD004190S KW - Serine KW - 452VLY9402 KW - 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester KW - 71145-03-4 KW - 1,4-dihydropyridine KW - 7M8K3P6I89 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Calcium Channels -- metabolism KW - Models, Molecular KW - 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester -- pharmacology KW - Rabbits KW - Electrophysiology KW - Protein Binding KW - Calcium Channel Agonists -- pharmacology KW - Serine -- chemistry KW - Phosphoric Monoester Hydrolases -- antagonists & inhibitors KW - Mutagenesis, Site-Directed KW - Threonine -- chemistry KW - Phosphorylation KW - Transfection KW - Adenosine Triphosphate -- metabolism KW - Okadaic Acid -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Cell Membrane -- metabolism KW - Protein Structure, Tertiary KW - Time Factors KW - Mutation KW - Cell Line KW - Cricetinae KW - Dihydropyridines -- pharmacology KW - Calcium Channels, L-Type -- physiology KW - Calcium Channels, L-Type -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73077458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modulation+of+cardiac+Ca%28V%291.2+channels+by+dihydropyridine+and+phosphatase+inhibitor+requires+Ser-1142+in+the+domain+III+pore+loop.&rft.au=Erxleben%2C+Christian%3BGomez-Alegria%2C+Claudio%3BDarden%2C+Thomas%3BMori%2C+Yasuo%3BBirnbaumer%2C+Lutz%3BArmstrong%2C+David+L&rft.aulast=Erxleben&rft.aufirst=Christian&rft.date=2003-03-04&rft.volume=100&rft.issue=5&rft.spage=2929&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 - 2003-05-13 N1 - Date created - 2003-03-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1999 Nov 26;274(48):33851-4 [10567342] Rev Physiol Biochem Pharmacol. 1999;139:33-87 [10453692] Biochem J. 2000 May 1;347 Pt 3:829-36 [10769189] Annu Rev Cell Dev Biol. 2000;16:521-55 [11031246] J Biol Chem. 2000 Dec 15;275(50):39710-7 [10984483] Circ Res. 2000 Dec 8;87(12):1095-102 [11110765] J Biol Chem. 2000 Dec 29;275(52):41504-11 [11022040] Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11024-31 [11572963] Nature. 2001 Nov 1;414(6859):43-8 [11689936] Am J Physiol Cell Physiol. 2001 Dec;281(6):C1743-56 [11698232] J Physiol. 2001 Dec 1;537(Pt 2):363-70 [11731570] J Neurochem. 2002 Sep;82(5):1065-76 [12358754] J Biol Chem. 2002 Nov 29;277(48):45969-76 [12198115] J Physiol. 2002 Dec 1;545(Pt 2):399-406 [12456820] Nature. 1984 Oct 11-17;311(5986):538-44 [6207437] J Mol Cell Cardiol. 1986 Jul;18(7):691-710 [2427730] Mol Pharmacol. 1986 Dec;30(6):571-84 [2431263] J Physiol. 1986 Sep;378:31-51 [2432251] Proc Natl Acad Sci U S A. 1987 Apr;84(8):2518-22 [2436233] Nature. 1988 Sep 22;335(6188):355-8 [2843772] Pflugers Arch. 1988 Aug;412(3):248-52 [2847114] Biochem J. 1988 Nov 15;256(1):283-90 [2851982] Proc Natl Acad Sci U S A. 1989 Sep;86(17):6816-20 [2549550] Pflugers Arch. 1989 Jul;414(3):257-64 [2476713] Pflugers Arch. 1990 Sep;417(1):58-66 [1705699] Naunyn Schmiedebergs Arch Pharmacol. 1991 Jan;343(1):83-9 [1903188] J Physiol. 1991 Jan;432:23-43 [1653319] Ann N Y Acad Sci. 1991;635:26-34 [1660238] J Physiol. 1992 Aug;454:673-88 [1335510] N Engl J Med. 1993 Apr 29;328(17):1244-51 [7681934] J Biol Chem. 1994 Jan 21;269(3):1635-40 [7507480] J Physiol. 1993 Oct;470:73-84 [8308752] Nucleic Acids Res. 1994 Nov 11;22(22):4673-80 [7984417] Circ Res. 1995 Mar;76(3):335-42 [7859380] J Physiol. 1995 May 1;484 ( Pt 3):583-92 [7623278] Biochim Biophys Acta. 1996 Jun 11;1281(2):205-12 [8664319] Biochem J. 1996 Sep 1;318 ( Pt 2):513-7 [8809040] J Biol Chem. 1997 Jan 31;272(5):2629-33 [9006896] J Mol Biol. 1997 Apr 18;267(5):1268-82 [9150411] Neuron. 1997 Jul;19(1):185-96 [9247274] J Gen Physiol. 1997 Nov;110(5):503-13 [9348323] Electrophoresis. 1997 Dec;18(15):2714-23 [9504803] Trends Pharmacol Sci. 1998 Mar;19(3):108-15 [9584627] J Biol Chem. 1998 Dec 25;273(52):34857-67 [9857013] Pflugers Arch. 1999 May;437(6):888-94 [10370067] Science. 1999 Jul 30;285(5428):763-6 [10427004] Nat Cell Biol. 2000 Mar;2(3):173-7 [10707089] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polyamines protect Escherichia coli cells from the toxic effect of oxygen. AN - 73068980; 12591940 AB - Wild-type Escherichia coli cells grow normally in 95% O(2)/5% CO(2). In contrast, cells that cannot make polyamines because of mutations in the biosynthetic pathway are rapidly killed by incubation in 95% O(2)/5% CO(2). Addition of polyamines prevents the toxic effect of oxygen, permitting cell survival and optimal growth. Oxygen toxicity can also be prevented if the growth medium contains an amino acid mixture or if the polyamine-deficient cells contain a manganese-superoxide dismutase (Mn-SOD) plasmid. Partial protection is afforded by the addition of 0.4 M sucrose or 0.4 M sorbitol to the growth medium. We also report that concentrations of H(2)O(2) that are nontoxic to wild-type cells or to mutant cells pretreated with polyamines kill polyamine-deficient cells. These results show that polyamines are important in protecting cells from the toxic effects of oxygen. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Chattopadhyay, Manas K AU - Tabor, Celia White AU - Tabor, Herbert AD - Laboratory of Biochemistry and Genetics, Building 8, Room 223, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/03/04/ PY - 2003 DA - 2003 Mar 04 SP - 2261 EP - 2265 VL - 100 IS - 5 SN - 0027-8424, 0027-8424 KW - Amines KW - 0 KW - Polyamines KW - Sorbitol KW - 506T60A25R KW - Sucrose KW - 57-50-1 KW - DNA KW - 9007-49-2 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Cadaverine KW - L90BEN6OLL KW - Oxygen KW - S88TT14065 KW - Spermidine KW - U87FK77H25 KW - Putrescine KW - V10TVZ52E4 KW - Index Medicus KW - Cadaverine -- pharmacology KW - Plasmids -- metabolism KW - DNA -- metabolism KW - Spermidine -- pharmacology KW - Sorbitol -- pharmacology KW - Hydrogen Peroxide -- pharmacology KW - Sorbitol -- chemistry KW - Amines -- chemistry KW - Air KW - Putrescine -- pharmacology KW - Polyamines -- chemistry KW - Chromatography, High Pressure Liquid KW - Polyamines -- pharmacology KW - Superoxide Dismutase -- pharmacology KW - Oxidative Stress KW - Polyamines -- metabolism KW - Sucrose -- pharmacology KW - Time Factors KW - Mutation KW - Cell Division KW - Escherichia coli -- metabolism KW - Oxygen -- metabolism KW - Escherichia coli -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73068980?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Polyamines+protect+Escherichia+coli+cells+from+the+toxic+effect+of+oxygen.&rft.au=Chattopadhyay%2C+Manas+K%3BTabor%2C+Celia+White%3BTabor%2C+Herbert&rft.aulast=Chattopadhyay&rft.aufirst=Manas&rft.date=2003-03-04&rft.volume=100&rft.issue=5&rft.spage=2261&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 - 2003-05-13 N1 - Date created - 2003-03-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Photochem Photobiol. 1978 Oct-Nov;28(4-5):733-41 [216032] Proc Natl Acad Sci U S A. 1986 Aug;83(16):6040-4 [3526348] J Bacteriol. 1980 Dec;144(3):952-6 [7002915] Annu Rev Pharmacol Toxicol. 1983;23:239-57 [6307121] J Bacteriol. 1983 Sep;155(3):1078-87 [6309739] Microbiol Rev. 1985 Mar;49(1):81-99 [3157043] EMBO J. 1986 Mar;5(3):623-30 [3011417] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8268-72 [3022287] J Biol Chem. 1987 Apr 5;262(10):4724-7 [3031031] Science. 1988 Apr 29;240(4852):640-2 [2834821] Science. 1988 Jun 3;240(4857):1302-9 [3287616] J Biol Chem. 1996 Aug 30;271(35):21037-40 [8702868] Gene. 1997 Mar 10;187(1):35-43 [9073064] J Exp Biol. 1998 Apr;201(Pt 8):1203-9 [9510531] Biochem Biophys Res Commun. 1998 Mar 6;244(1):298-303 [9514920] Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11140-5 [9736703] J Biol Chem. 1999 Feb 12;274(7):4202-6 [9933617] J Biol Chem. 1956 Jan;218(1):97-106 [13278318] Arch Microbiol. 2001 Jul;176(1-2):155-7 [11479716] Arch Biochem Biophys. 2002 Jun 1;402(1):104-9 [12051688] Proc Natl Acad Sci U S A. 1977 Sep;74(9):3642-6 [333444] Science. 1978 Sep 8;201(4359):875-80 [210504] J Biol Chem. 1978 Nov 25;253(22):8143-8 [213429] Methods Enzymol. 1978;53:382-93 [362127] Proc Natl Acad Sci U S A. 1990 Apr;87(7):2851-5 [2181453] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5872-6 [2062864] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11426-7 [1454830] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11428-30 [1454831] Proc Natl Acad Sci U S A. 1993 May 15;90(10):4693-7 [8506320] Free Radic Biol Med. 1994 Jan;16(1):29-33 [8299992] J Biol Chem. 1979 Dec 25;254(24):12419-26 [159306] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A spring-loaded state of NusG in its functional cycle is suggested by X-ray crystallography and supported by site-directed mutants. AN - 73042205; 12600194 AB - Transcription factor NusG is present in all prokaryotes, and orthologous proteins have also been identified in yeast and humans. NusG contains a 27-residue KOW motif, found in ribosomal protein L24 where it interacts with rRNA. NusG in Escherichia coli (EcNusG) is an essential protein and functions as a regulator of Rho-dependent transcription termination, phage lambda N and rRNA transcription antitermination, and phage HK022 Nun termination. Relative to EcNusG, Aquifex aeolicus NusG (AaNusG) and several other bacterial NusG proteins contain a variable insertion sequence of approximately 70 residues in the central region of the molecule. Recently, crystal structures of AaNusG in space groups P2(1) and I222 have been reported; the authors conclude that there are no conserved dimers among the contacting molecules in the crystals [Steiner, T., Kaiser, J. T., Marinkovic, S., Huber, R., and Wahl, M. C. (2002) EMBO J. 21, 4641-4653]. We have independently determined the structures of AaNusG also in two crystal forms, P2(1) and C222(1), and surprisingly found that AaNusG molecules form domain-swapped dimers in both crystals. Additionally, polymerization is also observed in the P2(1) crystal. A unique "ball-and-socket" junction dominates the intermolecular interactions within both oligomers. We believe that this interaction is a clue to the function of the molecule and propose a spring-loaded state in the functional cycle of NusG. The importance of the ball-and-socket junction for the function of NusG is supported by the functional analysis of site-directed mutants. JF - Biochemistry AU - Knowlton, J Randy AU - Bubunenko, Mikhail AU - Andrykovitch, Michelle AU - Guo, Wei AU - Routzahn, Karen M AU - Waugh, David S AU - Court, Donald L AU - Ji, Xinhua AD - Macromolecular Crystallography Laboratory, National Cancer Institute, P.O. Box B, Frederick, Maryland 21702, USA. Y1 - 2003/03/04/ PY - 2003 DA - 2003 Mar 04 SP - 2275 EP - 2281 VL - 42 IS - 8 SN - 0006-2960, 0006-2960 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - NusG protein, E coli KW - Peptide Elongation Factors KW - Transcription Factors KW - Phenylalanine KW - 47E5O17Y3R KW - Index Medicus KW - Phenylalanine -- chemistry KW - Escherichia coli Proteins -- chemistry KW - Protein Structure, Tertiary -- genetics KW - Amino Acid Substitution -- genetics KW - Dimerization KW - Molecular Sequence Data KW - Phenylalanine -- genetics KW - Crystallography, X-Ray KW - Amino Acid Sequence KW - Escherichia coli Proteins -- physiology KW - Structure-Activity Relationship KW - Escherichia coli Proteins -- genetics KW - Mutagenesis, Site-Directed KW - Transcription Factors -- physiology KW - Bacterial Proteins -- genetics KW - Peptide Elongation Factors -- physiology KW - Bacterial Proteins -- chemistry KW - Peptide Elongation Factors -- genetics KW - Transcription Factors -- chemistry KW - Transcription Factors -- genetics KW - Peptide Elongation Factors -- chemistry KW - Bacterial Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73042205?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=A+spring-loaded+state+of+NusG+in+its+functional+cycle+is+suggested+by+X-ray+crystallography+and+supported+by+site-directed+mutants.&rft.au=Knowlton%2C+J+Randy%3BBubunenko%2C+Mikhail%3BAndrykovitch%2C+Michelle%3BGuo%2C+Wei%3BRoutzahn%2C+Karen+M%3BWaugh%2C+David+S%3BCourt%2C+Donald+L%3BJi%2C+Xinhua&rft.aulast=Knowlton&rft.aufirst=J&rft.date=2003-03-04&rft.volume=42&rft.issue=8&rft.spage=2275&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-28 N1 - Date created - 2003-02-25 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1NPP; PDB; 1NPR N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BLM helicase-dependent transport of p53 to sites of stalled DNA replication forks modulates homologous recombination. AN - 73049963; 12606585 AB - Diverse functions, including DNA replication, recombination and repair, occur during S phase of the eukaryotic cell cycle. It has been proposed that p53 and BLM help regulate these functions. We show that p53 and BLM accumulated after hydroxyurea (HU) treatment, and physically associated and co-localized with each other and with RAD51 at sites of stalled DNA replication forks. HU-induced relocalization of BLM to RAD51 foci was p53 independent. However, BLM was required for efficient localization of either wild-type or mutated (Ser15Ala) p53 to these foci and for physical association of p53 with RAD51. Loss of BLM and p53 function synergistically enhanced homologous recombination frequency, indicating that they mediated the process by complementary pathways. Loss of p53 further enhanced the rate of spontaneous sister chromatid exchange (SCE) in Bloom syndrome (BS) cells, but not in their BLM-corrected counterpart, indicating that involvement of p53 in regulating spontaneous SCE is BLM dependent. These results indicate that p53 and BLM functionally interact during resolution of stalled DNA replication forks and provide insight into the mechanism of genomic fidelity maintenance by these nuclear proteins. JF - The EMBO journal AU - Sengupta, Sagar AU - Linke, Steven P AU - Pedeux, Remy AU - Yang, Qin AU - Farnsworth, Julie AU - Garfield, Susan H AU - Valerie, Kristoffer AU - Shay, Jerry W AU - Ellis, Nathan A AU - Wasylyk, Bohdan AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/03/03/ PY - 2003 DA - 2003 Mar 03 SP - 1210 EP - 1222 VL - 22 IS - 5 SN - 0261-4189, 0261-4189 KW - DNA-Binding Proteins KW - 0 KW - Nuclear Proteins KW - Tumor Suppressor Protein p53 KW - Serine KW - 452VLY9402 KW - RAD51 protein, human KW - EC 2.7.7.- KW - Rad51 Recombinase KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Bloom syndrome protein KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - Nuclear Proteins -- genetics KW - Cell Cycle -- physiology KW - Humans KW - Fibroblasts -- cytology KW - Protein Binding KW - Fibroblasts -- metabolism KW - Serine -- metabolism KW - Phosphorylation KW - Hydroxyurea -- metabolism KW - Models, Genetic KW - Bloom Syndrome KW - Nuclear Proteins -- metabolism KW - Cell Line KW - Bromodeoxyuridine -- metabolism KW - DNA-Binding Proteins -- metabolism KW - DNA Helicases -- metabolism KW - Active Transport, Cell Nucleus -- physiology KW - Recombination, Genetic KW - DNA Helicases -- genetics KW - Adenosine Triphosphatases -- metabolism KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Adenosine Triphosphatases -- genetics KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73049963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=BLM+helicase-dependent+transport+of+p53+to+sites+of+stalled+DNA+replication+forks+modulates+homologous+recombination.&rft.au=Sengupta%2C+Sagar%3BLinke%2C+Steven+P%3BPedeux%2C+Remy%3BYang%2C+Qin%3BFarnsworth%2C+Julie%3BGarfield%2C+Susan+H%3BValerie%2C+Kristoffer%3BShay%2C+Jerry+W%3BEllis%2C+Nathan+A%3BWasylyk%2C+Bohdan%3BHarris%2C+Curtis+C&rft.aulast=Sengupta&rft.aufirst=Sagar&rft.date=2003-03-03&rft.volume=22&rft.issue=5&rft.spage=1210&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-04-15 N1 - Date created - 2003-02-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Oncogene. 2000 Sep 14;19(39):4500-12 [11002423] EMBO J. 2000 Jul 3;19(13):3428-35 [10880455] Biochem Biophys Res Commun. 2001 Feb 16;281(1):212-9 [11178982] Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1036-41 [11158590] J Cell Biol. 2001 Apr 16;153(2):367-80 [11309417] Oncogene. 2001 Mar 1;20(9):1076-84 [11314044] Nature. 2001 May 17;411(6835):366-74 [11357144] Eur J Biochem. 2001 May;268(10):2764-72 [11358490] J Biol Chem. 2001 May 18;276(20):17276-80 [11278964] J Biol Chem. 2001 Jun 1;276(22):19375-81 [11278509] J Biol Chem. 2001 Aug 31;276(35):32948-55 [11399766] Genes Dev. 2001 Sep 15;15(18):2367-80 [11562347] Oncogene. 2001 Oct 4;20(45):6627-31 [11641788] Annu Rev Genomics Hum Genet. 2000;1:409-59 [11701636] Cancer Res. 2002 Jan 1;62(1):219-25 [11782381] Oncogene. 2002 Jan 17;21(3):488-92 [11821962] Cancer Res. 2002 Feb 15;62(4):1129-33 [11861393] J Cell Biol. 2002 Apr 1;157(1):19-30 [11916980] Oncogene. 2002 Mar 27;21(13):2079-88 [11960380] Cancer Res. 2002 May 15;62(10):2766-70 [12019152] J Biol Chem. 2002 Aug 30;277(35):31980-7 [12080066] Nature. 1974 Sep 13;251(5471):156-8 [4138930] Cancer Genet Cytogenet. 1986 May;22(1):1-18 [3513946] Cell. 1993 Nov 19;75(4):765-78 [8242748] Genes Dev. 1994 May 15;8(10):1235-46 [7926727] J Biol Chem. 1997 Mar 14;272(11):7532-9 [9054458] Nucleic Acids Res. 1997 Oct 1;25(19):3868-74 [9380510] Mutat Res. 1997 Dec;385(3):173-93 [9506887] Mutat Res. 1998 Dec 14;409(3):135-46 [9875289] Carcinogenesis. 1998 Dec;19(12):2115-20 [9886565] Genes Dev. 1999 Jun 1;13(11):1355-60 [10364153] Mol Cell Biol. 1999 Jul;19(7):5166-9 [10373565] Bioessays. 1999 Apr;21(4):286-94 [10377891] J Biol Chem. 1999 Oct 8;274(41):29463-9 [10506209] J Biol Chem. 1999 Dec 17;274(51):36031-4 [10593882] Hum Mol Genet. 2000 Feb 12;9(3):403-11 [10655550] Oncogene. 2000 Feb 3;19(5):632-9 [10698508] Genes Dev. 2000 Apr 15;14(8):927-39 [10783165] Nature. 2000 Apr 20;404(6780):897-900 [10786799] Trends Genet. 2000 Jun;16(6):259-64 [10827453] Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6504-8 [10823897] Genes Dev. 2000 Nov 15;14(22):2855-68 [11090133] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - First-line chemotherapy with fluorouracil and folinic acid for advanced colorectal cancer in elderly patients: a phase II study. AN - 85400635; pmid-12590234 AB - Colorectal cancer is one of the most common cancers in the elderly. Information on tolerability and efficacy of 5-Fluorouracil-based chemotherapy in such patients is limited. Primary aim of the study was to describe tolerability and activity of chemotherapy with the "de Gramont" schedule (FU bolus [400 mg/m ] + FU continuous infusion [600 mg/m ] + folinic acid [100 mg/m ] on days 1 and 2, every 2 weeks), in patients with advanced colorectal cancer aged 70 or older.Patients aged 70 or more, with stage IV colorectal cancer, ECOG performance status not worse than 2.Thirty-four patients were treated at two participating centers. Seven (20.6%, 95% exact CI = 8.7-37.9) had an objective response, complete in 3 and partial in 4 patients. Five cases of unacceptable toxicity were registered (2 cardiac, 1 each for liver, anemia and diarrhea). Fitting the statistical model to the observed data indicated that the treatment was sufficiently active and tolerated.The de Gramont scheme is active and tolerated in elderly patients with advanced colorectal cancer. JF - Journal of clinical gastroenterology AU - Daniele, Bruno AU - Rosati, Gerardo AU - Tambaro, Rosa AU - Ottaiano, Alessandro AU - De Maio, Ermelinda AU - Pignata, Sandro AU - Iaffaioli, Rosario Vincenzo AU - Rossi, Antonio AU - Manzione, Luigi AU - Gallo, Ciro AU - Perrone, Francesco AD - Medical Oncology, Clinical Trial Office, National Cancer Institute of Naples, Italy. Y1 - 2003/03// PY - 2003 DA - Mar 2003 SP - 228 EP - 233 VL - 36 IS - 3 SN - 0192-0790, 0192-0790 KW - Index Medicus KW - National Library of Medicine KW - Aged KW - Aged, 80 and over KW - Antimetabolites, Antineoplastic: administration & dosage KW - *Antimetabolites, Antineoplastic: therapeutic use KW - Antineoplastic Combined Chemotherapy Protocols: therapeutic use KW - *Colorectal Neoplasms: drug therapy KW - Colorectal Neoplasms: epidemiology KW - Comorbidity KW - Female KW - Fluorouracil: administration & dosage KW - *Fluorouracil: therapeutic use KW - Humans KW - Infusions, Intravenous KW - Leucovorin: administration & dosage KW - *Leucovorin: therapeutic use KW - Male KW - Prospective Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85400635?accountid=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=First-line+chemotherapy+with+fluorouracil+and+folinic+acid+for+advanced+colorectal+cancer+in+elderly+patients%3A+a+phase+II+study.&rft.au=Daniele%2C+Bruno%3BRosati%2C+Gerardo%3BTambaro%2C+Rosa%3BOttaiano%2C+Alessandro%3BDe+Maio%2C+Ermelinda%3BPignata%2C+Sandro%3BIaffaioli%2C+Rosario+Vincenzo%3BRossi%2C+Antonio%3BManzione%2C+Luigi%3BGallo%2C+Ciro%3BPerrone%2C+Francesco&rft.aulast=Daniele&rft.aufirst=Bruno&rft.date=2003-03-01&rft.volume=36&rft.issue=3&rft.spage=228&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+gastroenterology&rft.issn=01920790&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Recent advances in the understanding of the induction and regulation of mucosal inflammation. AN - 85366825; pmid-12698873 JF - Journal of gastroenterology AU - Strober, Warren AU - Fuss, Ivan J AU - Nakamura, Kazuhiko AU - Kitani, Atsushi AD - Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. Y1 - 2003/03// PY - 2003 DA - Mar 2003 SP - 55 EP - 58 VL - 38 Suppl 15 SN - 0944-1174, 0944-1174 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - *Colitis: etiology KW - *Colitis: physiopathology KW - Disease Models, Animal KW - Humans KW - *Inflammatory Bowel Diseases: etiology KW - *Inflammatory Bowel Diseases: physiopathology KW - *Intestinal Mucosa: physiopathology KW - Mice UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85366825?accountid=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+gastroenterology&rft.atitle=Recent+advances+in+the+understanding+of+the+induction+and+regulation+of+mucosal+inflammation.&rft.au=Strober%2C+Warren%3BFuss%2C+Ivan+J%3BNakamura%2C+Kazuhiko%3BKitani%2C+Atsushi&rft.aulast=Strober&rft.aufirst=Warren&rft.date=2003-03-01&rft.volume=38+Suppl+15&rft.issue=&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Journal+of+gastroenterology&rft.issn=09441174&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - The time course of perisaccadic receptive field shifts in the lateral intraparietal area of the monkey. AN - 85269369; pmid-12612015 AB - Neurons in the lateral intraparietal area of the monkey (LIP) have visual receptive fields in retinotopic coordinates when studied in a fixation task. However, in the period immediately surrounding a saccade these receptive fields often shift, so that a briefly flashed stimulus outside the receptive field will drive the neurons if the eye movement will bring the spatial location of that vanished stimulus into the receptive field. This is equivalent to a transient shift of the retinal receptive field. The process enables the monkey brain to process a stimulus in a spatially accurate manner after a saccade, even though the stimulus appeared only before the saccade. We studied the time course of this receptive field shift by flashing a task-irrelevant stimulus for 100 ms before, during, or after a saccade. The stimulus could appear in receptive field as defined by the fixation before the saccade (the current receptive field) or the receptive field as defined by the fixation after the saccade (the future receptive field). We recorded the activity of 48 visually responsive neurons in LIP of three hemispheres of two rhesus monkeys. We studied 45 neurons in the current receptive field task, in which the saccade removed the stimulus from the receptive field. Of these neurons 29/45 (64%) showed a significant decrement of response when the stimulus appeared 250 ms or less before the saccade, as compared with their activity during fixation. The average response decrement was 38% for those cells showing a significant (P < 0.05 by t-test) decrement. We studied 39 neurons in the future receptive field task, in which the saccade brought the spatial location of a recently vanished stimulus into the receptive field. Of these 32/39 (82%) had a significant response to stimuli flashed for 100 ms in the future receptive field, even 400 ms before the saccade. Neurons never responded to stimuli moved by the saccade from a point outside the receptive field to another point outside the receptive field. Neurons did not necessarily show any saccadic suppression for stimuli moved from one part of the receptive field to another by the saccade. Stimuli flashed <250 ms before the saccade-evoked responses in both the presaccadic and the postsaccadic receptive fields, resulting in an increase in the effective receptive field size, an effect that we suggest is responsible for perisaccadic perceptual inaccuracies. JF - Journal of Neurophysiology AU - Kusunoki Makoto AU - Goldberg, Michael E AD - Laboratory of Sensorimotor Research National Eye Institute Bethesda, Maryland 20892, USA. PY - 2003 SP - 1519 EP - 1527 VL - 89 IS - 3 SN - 0022-3077, 0022-3077 KW - Photic Stimulation KW - Support, U.S. Gov't, P.H.S. KW - Neurons KW - Animal KW - Space Perception KW - Macaca mulatta KW - Parietal Lobe KW - Saccades KW - Visual Fields KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85269369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=The+time+course+of+perisaccadic+receptive+field+shifts+in+the+lateral+intraparietal+area+of+the+monkey.&rft.au=Kusunoki+Makoto%3BGoldberg%2C+Michael+E&rft.aulast=Kusunoki+Makoto&rft.aufirst=&rft.date=2003-03-01&rft.volume=89&rft.issue=3&rft.spage=1519&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Convective distribution of macromolecules in the primate brain demonstrated using computerized tomography and magnetic resonance imaging. AN - 85229603; pmid-12650432 AB - OBJECT: Convection-enhanced delivery (CED), the delivery and distribution of drugs by the slow bulk movement of fluid in the extracellular space, allows delivery of therapeutic agents to large volumes of the brain at relatively uniform concentrations. This mode of drug delivery offers great potential for the treatment of many neurological disorders, including brain tumors, neurodegenerative diseases, and seizure disorders. An analysis of the treatment efficacy and toxicity of this approach requires confirmation that the infusion is distributed to the targeted region and that the drug concentrations are in the therapeutic range. METHODS: To confirm accurate delivery of therapeutic agents during CED and to monitor the extent of infusion in real time, albumin-linked surrogate tracers that are visible on images obtained using noninvasive techniques (iopanoic acid [IPA] for computerized tomography [CT] and Gd-diethylenetriamine pentaacetic acid for magnetic resonance [MR] imaging) were developed and investigated for their usefulness as surrogate tracers during convective distribution of a macromolecule. The authors infused albumin-linked tracers into the cerebral hemispheres of monkeys and measured the volumes of distribution by using CT and MR imaging. The distribution volumes measured by imaging were compared with tissue volumes measured using quantitative autoradiography with [14C]bovine serum albumin coinfused with the surrogate tracer. For in vivo determination of tracer concentration, the authors examined the correlation between the concentration of the tracer in brain homogenate standards and CT Hounsfield units. They also investigated the long-term effects of the surrogate tracer for CT scanning, IPA-albumin, on animal behavior, the histological characteristics of the tissue, and parenchymal toxicity after cerebral infusion. CONCLUSIONS: Distribution of a macromolecule to clinically significant volumes in the brain is possible using convection. The spatial dimensions of the tissue distribution can be accurately defined in vivo during infusion by using surrogate tracers and conventional imaging techniques, and it is expected that it will be possible to determine local concentrations of surrogate tracers in voxels of tissue in vivo by using CT scanning. Use of imaging surrogate tracers is a practical, safe, and essential tool for establishing treatment volumes during high-flow interstitial microinfusion of the central nervous system. JF - Journal of Neurosurgery AU - Nguyen, Tung T AU - Pannu, Yashdip S AU - Sung, Cynthia AU - Dedrick, Robert L AU - Walbridge, Stuart AU - Brechbiel, Martin W AU - Garmestani Kayhan AU - Beitzel, Markus AU - Yordanov, Alexander T AU - Oldfield, Edward H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke; National Institutes of Health, Bethesda, Maryland 20892-1414, USA. PY - 2003 SP - 584 EP - 590 VL - 98 IS - 3 SN - 0022-3085, 0022-3085 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85229603?accountid=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+Neurosurgery&rft.atitle=Convective+distribution+of+macromolecules+in+the+primate+brain+demonstrated+using+computerized+tomography+and+magnetic+resonance+imaging.&rft.au=Nguyen%2C+Tung+T%3BPannu%2C+Yashdip+S%3BSung%2C+Cynthia%3BDedrick%2C+Robert+L%3BWalbridge%2C+Stuart%3BBrechbiel%2C+Martin+W%3BGarmestani+Kayhan%3BBeitzel%2C+Markus%3BYordanov%2C+Alexander+T%3BOldfield%2C+Edward+H&rft.aulast=Nguyen&rft.aufirst=Tung&rft.date=2003-03-01&rft.volume=98&rft.issue=3&rft.spage=584&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Pathophysiology of headache associated with cough in patients with Chiari I malformation. AN - 85229294; pmid-12650413 AB - OBJECT: The aim of this study was to evaluate the pathophysiology underlying headache associated with cough in patients with Chiari I tonsillar abnormality. The authors hypothesized that peak intrathecal pressure during coughing is higher in patients with headache aggravated by cough than in patients without or in healthy volunteers. In addition, the authors evaluated the use of intrathecal pressure during cough as a means of assessing obstruction to the free flow of cerebrospinal fluid (CSF) at the craniocervical junction. METHODS: Twenty-six adult patients with Chiari I malformation and syringomyelia, four adult patients with Chiari I malformation without syringomyelia, and 15 healthy volunteers were prospectively studied. Testing before surgery included the following: 1) clinical evaluation for the presence of headache associated with cough; and 2) evaluation of lumbar subarachnoid pressure at rest, during three to five coughs, while performing the Valsalva maneuver, during jugular compression, and after removal of CSF. Patients underwent suboccipital craniectomy, C-1 laminectomy, and duraplasty. Testing was repeated 6 months after surgery. CONCLUSIONS: Peak intrathecal pressures during cough and at baseline were elevated in patients with headache associated with cough compared with either patients without headache or healthy volunteers. After surgery, intrathecal pressures during cough were significantly lower than preoperative values and headache aggravated by cough was resolved partially or completely. Headache linked to coughing in patients with Chiari I malformation is associated with sudden increased intrathecal pressure caused by obstruction to the free flow of CSF in the subarachnoid space. JF - Journal of Neurosurgery AU - Sansur, Charles A AU - Heiss, John D AU - DeVroom, Hetty L AU - Eskioglu, Eric AU - Ennis, Robert AU - Oldfield, Edward H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA. PY - 2003 SP - 453 EP - 458 VL - 98 IS - 3 SN - 0022-3085, 0022-3085 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85229294?accountid=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+Neurosurgery&rft.atitle=Pathophysiology+of+headache+associated+with+cough+in+patients+with+Chiari+I+malformation.&rft.au=Sansur%2C+Charles+A%3BHeiss%2C+John+D%3BDeVroom%2C+Hetty+L%3BEskioglu%2C+Eric%3BEnnis%2C+Robert%3BOldfield%2C+Edward+H&rft.aulast=Sansur&rft.aufirst=Charles&rft.date=2003-03-01&rft.volume=98&rft.issue=3&rft.spage=453&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - [Technical quality control of chest x-rays for the health surveillance of workers exposed to the risk of pneumoconiosis: proposal for a qualitative screening method]. TT - Controllo di qualità tecnica sui radiogrammi del torace effettuati per la sorveglianza sanitaria dei lavoratori esposti al rischio di pneumoconiosi: proposta di un metodo di screening qualitativo. AN - 73463652; 12852207 AB - The necessity of a qualitative screening has arisen from the fact that good technical quality is of fundamental importance for evaluating initial pneumoconiosis, for reducing inter- and intra-reader variability, for effective secondary prevention and for forensic medicine purposes. The authors report experience in use of a method to evaluate the quality of chest radiographs performed in health surveillance programs for workers at risk for development of pneumoconiosis. 747 postero-anterior chest radiographs concerning employees of 21 ceramic factories in the Province of Viterbo were examined. A standardized pattern was created for this evaluation. The pattern considers the main factors that can influence the quality of chest radiographs and assigns points for each of them. That factors are: 1) reproduced image of the lung's vascular structure, chiefly in the peripheral portions; 2) reproduced image of heart border, aorta, diaphragm; 3) deep inspiration; 4) symmetric image of the chest; 5) position of the scapulae; 6) visualization of the costal-phrenic angles; 7) technical impairments. The application of the method revealed that half of the chest radiographs examined had poor image quality for a suitable reading, in conformity with the ILO 1980 guidelines. The critical points are poor visualization of the lung's vascular structure due to overexposure or underexposure, technical impairments, non-correct scapulae position. The authors believe that the suggested method can be a useful instrument for self-testing the quality of chest radiographs performed in radiology centers and for the National Health Service to test the quality of chest radiographs performed in health surveillance programs. JF - La Medicina del lavoro AU - Manzari, Giovanna AU - Valenti, E AU - D'Epifanio, F AU - Quercia, A AU - Cardona, E AD - Dipartimento di Prevenzione, Servizio Prevenzione Igiene e Sicurezza nei Luoghi di Lavoro ASL Viterbo, Via Ferretti 169, 01033 Civita Castellana, VT. spisllciv@libero.it PY - 2003 SP - 242 EP - 249 VL - 94 IS - 2 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Medical Records KW - Artifacts KW - Diaphragm -- diagnostic imaging KW - Scapula -- diagnostic imaging KW - Lung -- diagnostic imaging KW - Respiration KW - Humans KW - Forms and Records Control KW - Anthropometry KW - Lung -- blood supply KW - Ribs -- diagnostic imaging KW - Heart -- diagnostic imaging KW - Adult KW - Aortography -- standards KW - Practice Guidelines as Topic KW - Epidemiological Monitoring KW - Italy -- epidemiology KW - Radiography, Thoracic -- standards KW - Ceramics KW - Pneumoconiosis -- diagnostic imaging KW - Environmental Monitoring -- standards KW - Mass Screening -- standards KW - Quality Control KW - Mass Screening -- methods KW - Environmental Monitoring -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73463652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BTechnical+quality+control+of+chest+x-rays+for+the+health+surveillance+of+workers+exposed+to+the+risk+of+pneumoconiosis%3A+proposal+for+a+qualitative+screening+method%5D.&rft.au=Manzari%2C+Giovanna%3BValenti%2C+E%3BD%27Epifanio%2C+F%3BQuercia%2C+A%3BCardona%2C+E&rft.aulast=Manzari&rft.aufirst=Giovanna&rft.date=2003-03-01&rft.volume=94&rft.issue=2&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-22 N1 - Date created - 2003-07-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of diet and housing on growth, body weight, survival and tumor incidences of B6C3F1 mice in chronic studies. AN - 73183353; 12696586 AB - Diet is one of the most important environmental factors influencing growth, body weight, survival, and age-related diseases of rodents in chronic studies. NIH-07 open formula diet was the selected diet for the NTP studies from 1980 to 1994. A new diet designated as NTP-2000 diet is the current diet for mice in the NTP studies beginning in 1994. This report is a summary of results of untreated control groups of B6C3F1 mice fed NTP-2000 or NIH-07 diet from several retrospective 2-year dosed-feed and inhalation studies for differences in growth, body weight, survival, and tumor incidences. The dosed-feed studies were conducted in 3 different facilities located in the United States, and all the inhalation studies were conducted in 1 facility. During dosed-feed studies, male and female mice housed in polycarbonate cages and fed the NTP-2000 diet had lower maximum body weights than those fed NIH-07 diet. However, during inhalation studies, mice housed in wire mesh cages and fed the NTP-2000 diet had higher maximum body weights than the mice fed NIH-07 diet. Survival was higher in groups fed NTP-2000 diet irrespective of sex, housing conditions, or body weight compared to the corresponding groups fed NIH-07 diet. Survival was higher in mice housed in polycarbonate cages irrespective of diet and sex compared to the respective sex and diet groups housed in wire mesh cages. During inhalation studies, survival of male and female mice fed NTP-2000 diet was higher than that of the groups fed NIH-07 diet, although the body weights of NTP-2000 diet groups were higher than those of the groups fed NIH-07 diet. When the NTP-2000 diet was used, male and female mice in dosed-feed studies and male mice in inhalation studies had markedly lower incidences of liver tumors than the corresponding groups fed NIH-07 diet. Significant decreases in the incidences of lung tumors were observed only in the male groups fed NTP-2000 diet during dosed-feed studies. These results suggest that body weight may not be the major contributing factor for mortality and liver tumors and that an interaction between diet and housing conditions appears to affect the growth, survival and tumor incidences of B6C3F1 mice. JF - Toxicologic pathology AU - Rao, Ghanta N AU - Crockett, Patrick W AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 2003 SP - 243 EP - 250 VL - 31 IS - 2 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Specific Pathogen-Free Organisms KW - Mice, Inbred Strains KW - Animals KW - Survival Rate KW - Food, Formulated KW - Carcinogenicity Tests KW - Mice KW - Male KW - Female KW - Toxicity Tests, Chronic -- methods KW - Animal Feed KW - Neoplasms -- mortality KW - Housing, Animal KW - Body Weight -- physiology KW - Diet UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73183353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Effect+of+diet+and+housing+on+growth%2C+body+weight%2C+survival+and+tumor+incidences+of+B6C3F1+mice+in+chronic+studies.&rft.au=Rao%2C+Ghanta+N%3BCrockett%2C+Patrick+W&rft.aulast=Rao&rft.aufirst=Ghanta&rft.date=2003-03-01&rft.volume=31&rft.issue=2&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-10-01 N1 - Date created - 2003-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cognitive-behavioral therapy plus contingency management for cocaine use: findings during treatment and across 12-month follow-up. AN - 73145384; 12665084 AB - Contingency management (CM) rapidly reduces cocaine use, but its effects subside after treatment. Cognitive-behavioral therapy (CBT) produces reductions months after treatment. Combined, the 2 might be complementary. One hundred ninety-three cocaine-using methadone-maintained outpatients were randomly assigned to 12 weeks of group therapy (CBT or a control condition) and voucher availability (CM contingent on cocaine-negative urine or noncontingent). Follow-ups occurred 3, 6, and 12 months posttreatment. Primary outcome was cocaine-negative urine (urinalysis 3 times/week during treatment and once at each follow-up). During treatment, initial effects of CM were dampened by CBT. Posttreatment, there were signs of additive benefits, significant in 3- versus 12-month contrasts. Former CBT participants were also more likely to acknowledge cocaine use and its effects and to report employment. JF - Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors AU - Epstein, David H AU - Hawkins, Wesley E AU - Covi, Lino AU - Umbricht, Annie AU - Preston, Kenzie L AD - Clinical Pharmacology and Therapeutics Branch, National Institute on Drug Abuse, Intramural Research Program Treatment Section, Baltimore, Maryland 21224, USA. depstein@intra.nida.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 73 EP - 82 VL - 17 IS - 1 SN - 0893-164X, 0893-164X KW - Analgesics, Opioid KW - 0 KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Regression Analysis KW - Analysis of Variance KW - Methadone -- therapeutic use KW - Combined Modality Therapy KW - Humans KW - Psychotherapy, Group -- methods KW - Opioid-Related Disorders -- drug therapy KW - Baltimore KW - Opioid-Related Disorders -- complications KW - Adult KW - Analgesics, Opioid -- therapeutic use KW - Follow-Up Studies KW - Female KW - Male KW - Token Economy KW - Behavior Therapy -- methods KW - Cocaine-Related Disorders -- rehabilitation KW - Cocaine-Related Disorders -- complications KW - Cognitive Therapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73145384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychology+of+addictive+behaviors+%3A+journal+of+the+Society+of+Psychologists+in+Addictive+Behaviors&rft.atitle=Cognitive-behavioral+therapy+plus+contingency+management+for+cocaine+use%3A+findings+during+treatment+and+across+12-month+follow-up.&rft.au=Epstein%2C+David+H%3BHawkins%2C+Wesley+E%3BCovi%2C+Lino%3BUmbricht%2C+Annie%3BPreston%2C+Kenzie+L&rft.aulast=Epstein&rft.aufirst=David&rft.date=2003-03-01&rft.volume=17&rft.issue=1&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Psychology+of+addictive+behaviors+%3A+journal+of+the+Society+of+Psychologists+in+Addictive+Behaviors&rft.issn=0893164X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-01 N1 - Date created - 2003-03-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Drug Alcohol Depend. 1996 Dec 2;43(1-2):23-37 [8957140] J Consult Clin Psychol. 1997 Apr;65(2):252-61 [9086688] Pharmacol Biochem Behav. 1997 Jul;57(3):419-27 [9218266] Addiction. 1997 Mar;92(3):297-302 [9219391] Am J Epidemiol. 1998 Apr 1;147(7):694-703 [9554609] J Psychopharmacol. 1998;12(1):8-14 [9584963] J Consult Clin Psychol. 1998 Oct;66(5):811-24 [9803700] Arch Gen Psychiatry. 2000 Apr;57(4):395-404 [10768702] J Consult Clin Psychol. 2000 Feb;68(1):64-72 [10710841] Drug Alcohol Depend. 2000 Feb 1;58(1-2):205-12 [10669073] Drug Alcohol Depend. 2000 Feb 1;58(1-2):9-25 [10669051] Drug Alcohol Depend. 2002 Jul 1;67(2):125-37 [12095662] J Consult Clin Psychol. 2001 Aug;69(4):643-54 [11550730] Addiction. 2000 Sep;95(9):1335-49 [11048353] J Subst Abuse Treat. 2002 Oct;23(3):191-7 [12392805] Arch Gen Psychiatry. 1981 Apr;38(4):381-9 [6260053] Arch Gen Psychiatry. 1996 May;53(5):409-15 [8624184] Arch Gen Psychiatry. 1996 Mar;53(3):217-24 [8611058] Arch Gen Psychiatry. 1994 Dec;51(12):989-97 [7979888] Arch Gen Psychiatry. 1994 Mar;51(3):177-87 [8122955] Am J Psychiatry. 1993 May;150(5):763-9 [8480823] J Nerv Ment Dis. 1985 Jul;173(7):412-23 [4009158] Psychopharmacol Bull. 1988;24(3):438-43 [3153505] Am J Psychiatry. 1991 Sep;148(9):1218-24 [1883001] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modeling gene-environment interactions in malignant melanoma. AN - 73132619; 12657431 AB - Many cancers are the pathological consequence of environmentally initiated disruptions to cellular genetic control mechanisms. For most cancers the relevant environmental carcinogens have not been identified, but one major exception is cutaneous malignant melanoma, for which the primary environmental agent is solar ultraviolet (UV) radiation. Hence, melanomagenesis represents a potential model of detrimental gene-environment interaction. Although the underlying genetic basis of melanoma is currently being elucidated, fundamental questions concerning UV and the mechanisms by which it operates remain unanswered. Significant progress has recently been made in creating UV-responsive, genetically tractable mouse models of melanoma that accurately recapitulate human disease. These models are providing novel insights into how the genome and environment interact in vivo. JF - Trends in molecular medicine AU - Merlino, Glenn AU - Noonan, Frances P AD - Laboratory of Molecular Biology, National Cancer Institute, Building 37, Room 5002, Bethesda, MD 20892-4264, USA. gmerlino@helix.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 102 EP - 108 VL - 9 IS - 3 SN - 1471-4914, 1471-4914 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - 0 KW - Index Medicus KW - Environment KW - Animals KW - Humans KW - Genes, cdc KW - Ultraviolet Rays -- adverse effects KW - Disease Models, Animal KW - Mice KW - Cyclin-Dependent Kinase Inhibitor p16 -- metabolism KW - Animals, Genetically Modified KW - Melanoma, Experimental -- genetics KW - Cyclin-Dependent Kinase Inhibitor p16 -- genetics KW - Melanoma, Experimental -- etiology KW - Melanoma -- genetics KW - Melanoma -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73132619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+molecular+medicine&rft.atitle=Modeling+gene-environment+interactions+in+malignant+melanoma.&rft.au=Merlino%2C+Glenn%3BNoonan%2C+Frances+P&rft.aulast=Merlino&rft.aufirst=Glenn&rft.date=2003-03-01&rft.volume=9&rft.issue=3&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Trends+in+molecular+medicine&rft.issn=14714914&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-12-18 N1 - Date created - 2003-03-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer. AN - 73100747; 12627929 AB - To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. Retrospective analysis of a randomized phase II trial. National Institutes of Health clinical research center. Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens. JF - Pharmacotherapy AU - Horne, McDonald K AU - Figg, William D AU - Arlen, Phil AU - Gulley, James AU - Parker, Catherine AU - Lakhani, Nehal AU - Parnes, Howard AU - Dahut, William L AD - Department of Laboratory Medicine, Hematology Service, W.G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 315 EP - 318 VL - 23 IS - 3 SN - 0277-0008, 0277-0008 KW - Taxoids KW - 0 KW - docetaxel KW - 15H5577CQD KW - Thalidomide KW - 4Z8R6ORS6L KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Humans KW - Retrospective Studies KW - Aged KW - Middle Aged KW - Male KW - Thalidomide -- adverse effects KW - Venous Thrombosis -- chemically induced KW - Paclitaxel -- analogs & derivatives KW - Antineoplastic Combined Chemotherapy Protocols KW - Paclitaxel -- therapeutic use KW - Thalidomide -- therapeutic use KW - Prostatic Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73100747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacotherapy&rft.atitle=Increased+frequency+of+venous+thromboembolism+with+the+combination+of+docetaxel+and+thalidomide+in+patients+with+metastatic+androgen-independent+prostate+cancer.&rft.au=Horne%2C+McDonald+K%3BFigg%2C+William+D%3BArlen%2C+Phil%3BGulley%2C+James%3BParker%2C+Catherine%3BLakhani%2C+Nehal%3BParnes%2C+Howard%3BDahut%2C+William+L&rft.aulast=Horne&rft.aufirst=McDonald&rft.date=2003-03-01&rft.volume=23&rft.issue=3&rft.spage=315&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-21 N1 - Date created - 2003-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methadone treatment induces attenuation of cerebrovascular deficits associated with the prolonged abuse of cocaine and heroin. AN - 73084025; 12629538 AB - Opiate replacement therapy has been useful in reducing heroin use and in keeping patients in treatment programs. However, neuropsychological and neurophysiological effects of this treatment regimen have not been evaluated systematically. To determine whether methadone treatment reduces the magnitude of cerebral blood flow alternations in polysubstance (heroin and cocaine) abusers, we compared blood flow parameters in control subjects (n=26), polysubstance abusers (n=28) maintained on methadone for 24 weeks, and polysubstance abusers (n=22) who were not seeking treatment. Blood flow velocity was recorded from the anterior and middle cerebral arteries using transcranial Doppler sonography on an outpatient visit. The pulsatility index, a measure of cerebrovascular resistance, was significantly (p&<0.05) increased in both groups of polysubstance abusers compared to control subjects. Increased pulsatility in the two groups of substance abusers suggests constriction of the small cortical arteries. Nevertheless, the methadone-maintained polysubstance abusers had significantly lower pulsatility values than the nontreatment substance-abusing group. These findings suggest that maintenance on methadone might have significant beneficial neurovascular effects on this population of patients. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Herning, Ronald I AU - Better, Warren E AU - Tate, Kimberly AU - Umbricht, Annie AU - Preston, Kenzie L AU - Cadet, Jean L AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse/IRP, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. rherning@intra.nida.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 562 EP - 568 VL - 28 IS - 3 SN - 0893-133X, 0893-133X KW - Methadone KW - UC6VBE7V1Z KW - Index Medicus KW - Anterior Cerebral Artery -- drug effects KW - Analysis of Variance KW - Cerebrovascular Circulation -- drug effects KW - Cerebrovascular Circulation -- physiology KW - Humans KW - Anterior Cerebral Artery -- diagnostic imaging KW - Middle Cerebral Artery -- diagnostic imaging KW - Middle Cerebral Artery -- drug effects KW - Adult KW - Ultrasonography, Doppler, Transcranial -- methods KW - Middle Aged KW - Female KW - Male KW - Cerebrovascular Disorders -- diagnostic imaging KW - Methadone -- therapeutic use KW - Heroin Dependence -- drug therapy KW - Cocaine-Related Disorders -- drug therapy KW - Cerebrovascular Disorders -- drug therapy KW - Cerebrovascular Disorders -- etiology KW - Heroin Dependence -- complications KW - Cocaine-Related Disorders -- complications KW - Heroin Dependence -- diagnostic imaging KW - Cocaine-Related Disorders -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73084025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Methadone+treatment+induces+attenuation+of+cerebrovascular+deficits+associated+with+the+prolonged+abuse+of+cocaine+and+heroin.&rft.au=Herning%2C+Ronald+I%3BBetter%2C+Warren+E%3BTate%2C+Kimberly%3BUmbricht%2C+Annie%3BPreston%2C+Kenzie+L%3BCadet%2C+Jean+L&rft.aulast=Herning&rft.aufirst=Ronald&rft.date=2003-03-01&rft.volume=28&rft.issue=3&rft.spage=562&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 - 2003-05-07 N1 - Date created - 2003-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of extracellular sodium on mu-opioid receptors coupled to potassium channels coexpressed in Xenopus oocytes. AN - 73083486; 12632192 AB - Wild-type or mutant H297N or H297Q of the mu-opioid receptor were co-expressed with the inwardly rectifying potassium channel GIRK1 in oocytes from Xenopus laevis. Under voltage clamp, pairs of concentration response curves were generated using the agonist normorphine in a bathing medium containing 38.5 mM sodium or an identical medium in which the sodium was replaced by an equimolar concentration of choline. The maximum currents were greater in the presence of sodium by about 30% at wild-type receptors and by about 100% at the mutant receptors. The EC(50) values tended to increase somewhat as well, though these differences reached statistical significance only for the mutant H297Q. Flame photometry detected no change in the intracellular sodium or potassium concentrations of oocytes, suggesting that the effect of sodium was solely extracellular. Thus sodium, long known for its effects on in vitro ligand binding at mu-opioid receptors, also affects overall transduction as revealed in the Xenopus oocyte model of a complete, living cell system. JF - Pflugers Archiv : European journal of physiology AU - Oz, Murat AU - Spivak, Charles E AD - Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, DH HS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 716 EP - 720 VL - 445 IS - 6 SN - 0031-6768, 0031-6768 KW - G Protein-Coupled Inwardly-Rectifying Potassium Channels KW - 0 KW - Potassium Channels KW - Potassium Channels, Inwardly Rectifying KW - Receptors, Opioid, mu KW - Sodium KW - 9NEZ333N27 KW - Choline KW - N91BDP6H0X KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Choline -- pharmacology KW - Xenopus laevis KW - Animals KW - Patch-Clamp Techniques KW - Membrane Potentials -- physiology KW - Potassium -- pharmacology KW - Mutagenesis -- physiology KW - Oocytes -- physiology KW - Membrane Potentials -- drug effects KW - Gene Expression -- physiology KW - Female KW - Potassium Channels -- metabolism KW - Potassium Channels -- genetics KW - Receptors, Opioid, mu -- metabolism KW - Sodium -- pharmacology KW - Receptors, Opioid, mu -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73083486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pflugers+Archiv+%3A+European+journal+of+physiology&rft.atitle=Effects+of+extracellular+sodium+on+mu-opioid+receptors+coupled+to+potassium+channels+coexpressed+in+Xenopus+oocytes.&rft.au=Oz%2C+Murat%3BSpivak%2C+Charles+E&rft.aulast=Oz&rft.aufirst=Murat&rft.date=2003-03-01&rft.volume=445&rft.issue=6&rft.spage=716&rft.isbn=&rft.btitle=&rft.title=Pflugers+Archiv+%3A+European+journal+of+physiology&rft.issn=00316768&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-11-25 N1 - Date created - 2003-03-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. AN - 73073154; 12610195 AB - The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy. Between April 1999 and October 2000, forty-seven patients were randomly assigned to either group one, which received vitamin E supplementation during cisplatin chemotherapy, or to group two, which received cisplatin chemotherapy alone. Alpha-tocopherol (vitamin E; 300 mg/d) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment. For preclinical studies, nude mice carrying the human melanoma tumor were treated with cisplatin alone or in combination with vitamin E. Twenty-seven patients completed six cycles of cisplatin chemotherapy: 13 patients in group one and 14 patients in group two. The incidence of neurotoxicity was significantly lower in group one (30.7%) than it was in group two (85.7%; P <.01). The severity of neurotoxicity, measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters, was significantly lower in patients who were supplemented with vitamin E than in patients who were not supplemented with vitamin E (2 v 4.7, P <.01). The results of the preclinical studies showed that when cisplatin was combined with vitamin E, no differences were observed in tumor weight inhibition, tumor growth delay, or life span as compared with treatment with cisplatin alone. Supplementation of patients receiving cisplatin chemotherapy with vitamin E decreases the incidence and severity of peripheral neurotoxicity. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Pace, Andrea AU - Savarese, Antonella AU - Picardo, Mauro AU - Maresca, Vittoria AU - Pacetti, Umberto AU - Del Monte, Girolamo AU - Biroccio, Annamaria AU - Leonetti, Carlo AU - Jandolo, Bruno AU - Cognetti, Francesco AU - Bove, Loredana AD - Neuroscience Department, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy. pace@ifo.it Y1 - 2003/03/01/ PY - 2003 DA - 2003 Mar 01 SP - 927 EP - 931 VL - 21 IS - 5 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Antioxidants KW - Neuroprotective Agents KW - Vitamin E KW - 1406-18-4 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Animals KW - Humans KW - Cytoprotection KW - Aged KW - Melanoma, Experimental -- prevention & control KW - Mice KW - Electrophysiology KW - Drug Therapy, Combination KW - Adult KW - Middle Aged KW - Dietary Supplements KW - Drug Evaluation, Preclinical KW - Female KW - Male KW - Peripheral Nervous System Diseases -- physiopathology KW - Neoplasms -- drug therapy KW - Cisplatin -- therapeutic use KW - Antioxidants -- therapeutic use KW - Vitamin E -- therapeutic use KW - Cisplatin -- adverse effects KW - Neuroprotective Agents -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Peripheral Nervous System Diseases -- prevention & control KW - Peripheral Nervous System Diseases -- chemically induced KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73073154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neuroprotective+effect+of+vitamin+E+supplementation+in+patients+treated+with+cisplatin+chemotherapy.&rft.au=Pace%2C+Andrea%3BSavarese%2C+Antonella%3BPicardo%2C+Mauro%3BMaresca%2C+Vittoria%3BPacetti%2C+Umberto%3BDel+Monte%2C+Girolamo%3BBiroccio%2C+Annamaria%3BLeonetti%2C+Carlo%3BJandolo%2C+Bruno%3BCognetti%2C+Francesco%3BBove%2C+Loredana&rft.aulast=Pace&rft.aufirst=Andrea&rft.date=2003-03-01&rft.volume=21&rft.issue=5&rft.spage=927&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-03-28 N1 - Date created - 2003-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genotoxic profiling of MCF-7 breast cancer cell line elucidates gene expression modifications underlying toxicity of the anticancer drug 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole. AN - 73061324; 12606787 AB - A candidate antitumor agent, 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F-203), was empirically discovered through the National Cancer Institute's Anticancer Drug Screen from a unique growth inhibitory-response profile, indicating a novel mechanism of action. 5F-203 activates the CYP1 family of cytochrome P450, involving aryl hydrocarbon receptor translocation into the nucleus. To characterize more completely the pathways involved in 5F-203 toxicity, cDNA microarrays were used to determine gene expression changes in MCF-7, a 5F-203-sensitive breast cancer cell line, after treatment with 1 microM 5F-203. The mRNA expression of CYP1A1 and CYP1B1 were both increased approximately 20-fold after 24 h, but less after 6 h of treatment, confirming previous results. However, the most pronounced drug-induced change was in the PLAB gene, encoding one of the bone morphogenic proteins in the transforming growth factor-beta (TGF-beta) superfamily. Other induced gene expressions included the apoptosis-initiating receptor TNFRSF6 (CD95/FAS), the DNA-damage response genes CDKN1A (p21/Cip1), p53-induced gene-3, and DNA binding protein 2. In contrast, the transcription factor c-Myc showed reduced expression. Western blot analysis also showed induction of p53 protein expression in response to 5F-203 treatment. In contrast to the MCF-7 data, MDA-MB-435, a cancer cell line resistant to 5F-203, showed no change in expression of any of these genes or the p53 protein under the same conditions of 5F-203 treatment. These data are consistent with the idea that CYP1A1 and CYP1B1 activation leads to 5F-203 toxicity through DNA damage-induced apoptosis, as well as signaling through a variant member of the TGF-beta superfamily. JF - Molecular pharmacology AU - Monks, Anne AU - Harris, Erik AU - Hose, Curtis AU - Connelly, John AU - Sausville, Edward A AD - SAIC-Frederick Inc., Screening Technologies Branch, Laboratory of Functional Genomics, National Cancer Institute--Frederick, National Institutes of Health, Frederick, Maryland, USA. monks@dtpax2.ncifcrf.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 766 EP - 772 VL - 63 IS - 3 SN - 0026-895X, 0026-895X KW - 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole KW - 0 KW - Antineoplastic Agents KW - Thiazoles KW - Index Medicus KW - Gene Expression Profiling KW - Tumor Cells, Cultured KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Reverse Transcriptase Polymerase Chain Reaction KW - Female KW - Thiazoles -- pharmacology KW - Gene Expression -- drug effects KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- pathology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73061324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Genotoxic+profiling+of+MCF-7+breast+cancer+cell+line+elucidates+gene+expression+modifications+underlying+toxicity+of+the+anticancer+drug+2-%284-amino-3-methylphenyl%29-5-fluorobenzothiazole.&rft.au=Monks%2C+Anne%3BHarris%2C+Erik%3BHose%2C+Curtis%3BConnelly%2C+John%3BSausville%2C+Edward+A&rft.aulast=Monks&rft.aufirst=Anne&rft.date=2003-03-01&rft.volume=63&rft.issue=3&rft.spage=766&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-12 N1 - Date created - 2003-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thimerosal and autism? AN - 73056924; 12612255 JF - Pediatrics AU - Nelson, Karin B AU - Bauman, Margaret L AD - Neuroepidemiology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892-1447, USA. knelson@helix.nih.gov Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 674 EP - 679 VL - 111 IS - 3 KW - Preservatives, Pharmaceutical KW - 0 KW - Vaccines KW - Thimerosal KW - 2225PI3MOV KW - Abridged Index Medicus KW - Index Medicus KW - Mercury Poisoning -- pathology KW - Global Health KW - Diagnosis, Differential KW - Humans KW - Brain -- pathology KW - Child KW - Mercury Poisoning -- diagnosis KW - Adolescent KW - Vaccines -- adverse effects KW - Thimerosal -- adverse effects KW - Autistic Disorder -- chemically induced KW - Autistic Disorder -- diagnosis KW - Preservatives, Pharmaceutical -- poisoning KW - Thimerosal -- poisoning KW - Preservatives, Pharmaceutical -- adverse effects KW - Autistic Disorder -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73056924?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Thimerosal+and+autism%3F&rft.au=Nelson%2C+Karin+B%3BBauman%2C+Margaret+L&rft.aulast=Nelson&rft.aufirst=Karin&rft.date=2003-03-01&rft.volume=111&rft.issue=3&rft.spage=674&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=1098-4275&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-06-02 N1 - Date created - 2003-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of renal cell repair and regeneration after acute renal failure. AN - 73056764; 12604664 AB - In many cases, acute renal failure (ARF) is the result of proximal tubular cell injury and death and can arise in a variety of clinical situations, especially following renal ischemia and drug or toxicant exposure. Although much research has focused on the cellular events leading to ARF, less emphasis has been placed on the mechanisms of renal cell repair and regeneration, although ARF is reversed in over half of those who acquire it. Studies using in vivo and in vitro models have demonstrated the importance of proliferation, migration, and repair of physiological functions of injured renal proximal tubular cells (RPTC) in the reversal of ARF. Growth factors have been shown to produce migration and proliferation of injured RPTC, although the specific mechanisms through which growth factors promote renal regeneration in vivo are unclear. Recently, interactions between integrins and extracellular matrix proteins such as collagen IV were shown to promote the repair of physiological functions in injured RPTC. Specifically, collagen IV synthesis and deposition following cellular injury restored integrin polarity and promoted repair of mitochondrial function and active Na(+) transport. Furthermore, exogenous collagen IV, but not collagen I, fibronectin, or laminin, promoted the repair of physiological functions without stimulating proliferation. These findings suggest the importance of establishing and/or maintaining collagen IV-integrin interactions in the stimulation of repair of physiological functions following sublethal cellular injury. Furthermore, the pathway that stimulates repair is distinct from that of proliferation and migration and may be a viable target for pharmacological intervention. JF - The Journal of pharmacology and experimental therapeutics AU - Nony, Paul A AU - Schnellmann, Rick G AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 905 EP - 912 VL - 304 IS - 3 SN - 0022-3565, 0022-3565 KW - Index Medicus KW - Cell Movement KW - Humans KW - Acute Kidney Injury -- pathology KW - Regeneration KW - Kidney Tubules, Proximal -- injuries KW - Acute Kidney Injury -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73056764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanisms+of+renal+cell+repair+and+regeneration+after+acute+renal+failure.&rft.au=Nony%2C+Paul+A%3BSchnellmann%2C+Rick+G&rft.aulast=Nony&rft.aufirst=Paul&rft.date=2003-03-01&rft.volume=304&rft.issue=3&rft.spage=905&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 - 2003-04-21 N1 - Date created - 2003-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human renal organic anion transporter 1-dependent uptake and toxicity of mercuric-thiol conjugates in Madin-Darby canine kidney cells. AN - 73055285; 12606766 AB - Mercuric ions are highly reactive and form a variety of organic complexes or conjugates in vivo. The renal proximal tubule is a primary target for mercury uptake and toxicity, and circumstantial evidence implicates organic anion transporters in these processes. To test this hypothesis directly, the transport and toxicity of mercuric-thiol conjugates were characterized in a Madin-Darby canine kidney cell line stably transfected with the human organic anion transporter 1 (hOAT1). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-terazolium bromide assays (for mitochondrial dehydrogenase) confirmed that mercuric conjugates of the thiols N-acetylcysteine (NAC), cysteine, or glutathione were more toxic in hOAT1-transfected cells than in the nontransfected cells. The NAC-Hg(2+) conjugate was most cytotoxic, inducing greater than 50% cellular death over 18 h at a concentration of 100 microM. The cytotoxic effects were fully reversed by probenecid (an OAT1 inhibitor) and partially reversed by p-aminohippurate (an OAT1 substrate). Toxicity of this conjugate was reduced by the OAT1-exchangeable dicarboxylates alpha-ketoglutarate, glutarate, and adipate, but not by succinate, a nonexchangeable dicarboxylate. (203)Hg-uptake studies showed probenecid-sensitive uptake of mercury-thiol conjugates in the hOAT1-transfected cells. The apparent K(m) for the NAC-Hg(2+) conjugate was 44 +/- 9 microM. Uptake of the NAC-Hg(2+) conjugate was cis-inhibited by glutarate, but not by methylsuccinate, paralleling their effects on toxicity. Probenecid-sensitive transport of the NAC-Hg(2+) conjugate was also shown to occur in Xenopus laevis oocytes expressing the hOAT1 or the rOAT3 transporters, suggesting that OAT3 may also transport thiol-Hg(2+) conjugates. Thus, renal accumulation and toxicity of thiol-Hg(2+) conjugates may depend in part on the activity of the organic transport system. JF - Molecular pharmacology AU - Aslamkhan, Amy G AU - Han, Yong-Hae AU - Yang, Xiao-Ping AU - Zalups, Rudolfs K AU - Pritchard, John B AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 590 EP - 596 VL - 63 IS - 3 SN - 0026-895X, 0026-895X KW - Mercury Isotopes KW - 0 KW - Organic Anion Transport Protein 1 KW - Mercury KW - FXS1BY2PGL KW - Index Medicus KW - Animals KW - Cell Survival -- drug effects KW - Cells, Cultured KW - Humans KW - Mercury Isotopes -- metabolism KW - Kidney -- cytology KW - Dogs KW - Biological Transport KW - Organic Anion Transport Protein 1 -- metabolism KW - Mercury -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73055285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Human+renal+organic+anion+transporter+1-dependent+uptake+and+toxicity+of+mercuric-thiol+conjugates+in+Madin-Darby+canine+kidney+cells.&rft.au=Aslamkhan%2C+Amy+G%3BHan%2C+Yong-Hae%3BYang%2C+Xiao-Ping%3BZalups%2C+Rudolfs+K%3BPritchard%2C+John+B&rft.aulast=Aslamkhan&rft.aufirst=Amy&rft.date=2003-03-01&rft.volume=63&rft.issue=3&rft.spage=590&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-05-12 N1 - Date created - 2003-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular determinants of glucocorticoid receptor mobility in living cells: the importance of ligand affinity. AN - 73055117; 12612067 AB - The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), which is activated upon ligand binding, and can alter the expression of target genes either by transrepression or transactivation. We have applied FRAP (fluorescence recovery after photobleaching) to quantitatively assess the mobility of the yellow fluorescent protein (YFP)-tagged human GR alpha-isoform (hGRalpha) in the nucleus of transiently transfected COS-1 cells and to elucidate determinants of its mobility. Addition of the high-affinity agonist dexamethasone markedly decreases the mobility of the receptor in a concentration-dependent manner, whereas low-affinity ligands like corticosterone decrease the mobility to a much lesser extent. Analysis of other hGRalpha ligands differing in affinity suggests that it is the affinity of the ligand that is a major determinant of the decrease in mobility. Similar results were observed for two hGRalpha antagonists, the low-affinity antagonist ZK98299 and the high-affinity antagonist RU486. The effect of ligand affinity on mobility was confirmed with the hGRalpha mutant Q642V, which has an altered affinity for triamcinolone acetonide, dexamethasone, and corticosterone. Analysis of hGRalpha deletion mutants indicates that both the DNA-binding domain and the ligand-binding domain of the receptor are required for a maximal ligand-induced decrease in receptor mobility. Interestingly, the mobility of transfected hGRalpha differs among cell types. Finally, the proteasome inhibitor MG132 immobilizes a subpopulation of unliganded receptors, via a mechanism requiring the DNA-binding domain and the N-terminal part of the ligand-binding domain. Ligand binding makes the GR resistant to the immobilizing effect of MG132, and this effect depends on the affinity of the ligand. Our data suggest that ligand binding induces a conformational change of the receptor which is dependent on the affinity of the ligand. This altered conformation decreases the mobility of the receptor, probably by targeting the receptor to relatively immobile nuclear domains with which it transiently associates. In addition, this conformational change blocks immobilization of the receptor by MG132. JF - Molecular and cellular biology AU - Schaaf, Marcel J M AU - Cidlowski, John A AD - Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH/DHHS, 111 Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 1922 EP - 1934 VL - 23 IS - 6 SN - 0270-7306, 0270-7306 KW - Bacterial Proteins KW - 0 KW - Fluorescent Dyes KW - Gonanes KW - Leupeptins KW - Ligands KW - Luminescent Proteins KW - Multienzyme Complexes KW - Protease Inhibitors KW - Protein Isoforms KW - Receptors, Glucocorticoid KW - Recombinant Fusion Proteins KW - glucocorticoid receptor alpha KW - yellow fluorescent protein, Bacteria KW - Mifepristone KW - 320T6RNW1F KW - Dexamethasone KW - 7S5I7G3JQL KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Triamcinolone Acetonide KW - F446C597KA KW - onapristone KW - H6H7G23O3N KW - benzyloxycarbonylleucyl-leucyl-leucine aldehyde KW - RF1P63GW3K KW - Corticosterone KW - W980KJ009P KW - Cortodoxone KW - WDT5SLP0HQ KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Photochemistry KW - Fluorescent Dyes -- analysis KW - Microscopy, Confocal KW - Protease Inhibitors -- pharmacology KW - Multienzyme Complexes -- metabolism KW - Animals KW - Cell Nucleus -- metabolism KW - Luminescent Proteins -- analysis KW - Dexamethasone -- pharmacology KW - Humans KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Hydrocortisone -- pharmacology KW - Leupeptins -- pharmacology KW - Cytoplasm -- metabolism KW - Cysteine Endopeptidases -- metabolism KW - COS Cells -- metabolism KW - Bacterial Proteins -- analysis KW - Genes, Reporter KW - Corticosterone -- pharmacology KW - Cortodoxone -- pharmacology KW - Gonanes -- pharmacology KW - Sequence Deletion KW - HeLa Cells -- metabolism KW - Cell Line -- metabolism KW - Protein Conformation -- drug effects KW - Protein Binding KW - Mifepristone -- pharmacology KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Transfection KW - Cercopithecus aethiops KW - Kidney KW - Triamcinolone Acetonide -- pharmacology KW - Protein Structure, Tertiary KW - Active Transport, Cell Nucleus KW - Receptors, Glucocorticoid -- drug effects KW - Receptors, Glucocorticoid -- chemistry KW - Receptors, Glucocorticoid -- antagonists & inhibitors KW - Receptors, Glucocorticoid -- metabolism KW - Receptors, Glucocorticoid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73055117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+determinants+of+glucocorticoid+receptor+mobility+in+living+cells%3A+the+importance+of+ligand+affinity.&rft.au=Schaaf%2C+Marcel+J+M%3BCidlowski%2C+John+A&rft.aulast=Schaaf&rft.aufirst=Marcel+J&rft.date=2003-03-01&rft.volume=23&rft.issue=6&rft.spage=1922&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 - 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Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective induction of high avidity CTL by altering the balance of signals from APC. AN - 73038626; 12594278 AB - High avidity CTL are most effective at clearing viruses and cancer cells. Therefore, understanding the mechanisms involved in induction of high avidity CTL is critical for effective vaccines. However, no vaccine approach to selectively induce high avidity CTL in vivo has been discovered. In a new approach, signals from MHC class I (signal 1) and costimulatory molecules (signal 2) were adjusted by varying Ag dose and by use of recombinant poxvirus expressing a triad of costimulatory molecules (B7-1, ICAM-1, and LFA-3), respectively. Independent of CTL avidity, a strong signal 1 resulted in an increased frequency of CD8(+) CTL. However, a strong signal 2 was necessary for the induction of high avidity CD8(+) CTL that killed target cells more efficiently, and signal 2 played a more crucial role in the absence of a strong signal 1. Only CTL induced with strong signal 2 killed tumor cells endogenously expressing low levels of Ag. Signal 2 contributed to the induction of high avidity CD8(+) CTL in both primary and secondary responses. Thus, although signal 2 has been known to increase the quantity of CTL response, in this study we show that it also improves the quality of CTL response. Our data also suggested that dendritic cells play an important role in induction of high avidity CD8(+) CTL in vivo. This strategy to selectively induce higher avidity CTL may lead to more effective vaccines for viruses and cancer. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Oh, SangKon AU - Hodge, James W AU - Ahlers, Jeffrey D AU - Burke, Donald S AU - Schlom, Jeffrey AU - Berzofsky, Jay A AD - Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2003/03/01/ PY - 2003 DA - 2003 Mar 01 SP - 2523 EP - 2530 VL - 170 IS - 5 SN - 0022-1767, 0022-1767 KW - Antigens, CD58 KW - 0 KW - Antigens, CD80 KW - Cancer Vaccines KW - Epitopes, T-Lymphocyte KW - Peptides KW - Vaccines, Synthetic KW - rV-Tricom KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Cytotoxicity Tests, Immunologic -- methods KW - CD8-Positive T-Lymphocytes -- metabolism KW - Antigens, CD58 -- physiology KW - Humans KW - Antigens, CD80 -- genetics KW - Immunization, Secondary KW - Intercellular Adhesion Molecule-1 -- genetics KW - Mice, Inbred BALB C KW - Intercellular Adhesion Molecule-1 -- physiology KW - Lymphocyte Count KW - Tumor Cells, Cultured KW - Cell Division -- immunology KW - Vaccines, Synthetic -- genetics KW - Antigens, CD80 -- physiology KW - 3T3 Cells KW - Peptides -- metabolism KW - Peptides -- immunology KW - Interferon-gamma -- biosynthesis KW - Mice KW - Epitopes, T-Lymphocyte -- analysis KW - Vaccines, Synthetic -- pharmacology KW - CD8-Positive T-Lymphocytes -- cytology KW - Antigens, CD58 -- genetics KW - CD8-Positive T-Lymphocytes -- immunology KW - Dose-Response Relationship, Immunologic KW - Mice, Inbred C57BL KW - Poxviridae -- genetics KW - Poxviridae -- immunology KW - Cell Division -- genetics KW - Female KW - Lymphocyte Activation -- genetics KW - Dendritic Cells -- immunology KW - Dendritic Cells -- virology KW - Dendritic Cells -- metabolism KW - T-Lymphocytes, Cytotoxic -- cytology KW - Signal Transduction -- genetics KW - Signal Transduction -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Cytotoxicity, Immunologic -- genetics KW - Dendritic Cells -- transplantation KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Antigen Presentation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73038626?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Selective+induction+of+high+avidity+CTL+by+altering+the+balance+of+signals+from+APC.&rft.au=Oh%2C+SangKon%3BHodge%2C+James+W%3BAhlers%2C+Jeffrey+D%3BBurke%2C+Donald+S%3BSchlom%2C+Jeffrey%3BBerzofsky%2C+Jay+A&rft.aulast=Oh&rft.aufirst=SangKon&rft.date=2003-03-01&rft.volume=170&rft.issue=5&rft.spage=2523&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 - 2003-05-21 N1 - Date created - 2003-02-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of metoprolol, B1-adrenoceptor antagonist, thromboxane A2 and nitric oxide in CsA-induced hypertension. AN - 73036968; 12591008 AB - Chronic treatment with cyclosporine A (CsA), a potent immunosuppressive agent, is associated with the development of arterial hypertension. The effect of CsA on vascular responses was determined in Sprague-Dawley rats and rat aortic rings. Male rats weighing 250-300 g were given either CsA (25mg/kg/day) in olive oil or vehicle by intraperitoneal (ip) injection for 7 days. CsA administration produced a 42% increase (P<0.001) in mean arterial pressure (MAP) which reached a plateau after 3 days. The level of both nitrate/nitrite (NO(2)/NO(3)), metabolites of nitric oxide (NO), decreased by 50% (P<0.001), but the level of thromboxane A2 (TBXA2) increased by 75% (P<0.001), in the urine. When 10(-9)M of CsA was added acutely to intact aortic rings from untreated rats, NO(2)/NO(3) production decreased by 83% (P<0.011), but TBXA2 production increased by 86% (P<0.001). The effects of CsA were reversed both in vivo and in vitro by pretreatment with metoprolol (15 mg/kg/day ip), B1-adrenoceptor antagonist. There were no changes in MAP and tension in rats treated with metoprolol alone. In addition, in aorta of rats that were treated with CsA ip for 7 days, CsA significantly activated protein kinase C (PKC) translocation. This suggests that PKC mediate, in part, CsA-induced hypertension. In summary, CsA inhibits endothelial NO formation, activate PKC, and increase TBXA2 production, with resulting increase in MAP, and this changes can be overcome by pretreatment with metoprolol. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Oriji, Gibson K AD - Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. doriji@aol.com Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 233 EP - 238 VL - 68 IS - 3 SN - 0952-3278, 0952-3278 KW - Adrenergic beta-Antagonists KW - 0 KW - Immunosuppressive Agents KW - Nitric Oxide KW - 31C4KY9ESH KW - Thromboxane A2 KW - 57576-52-0 KW - Cyclosporine KW - 83HN0GTJ6D KW - Protein Kinase C KW - EC 2.7.11.13 KW - Metoprolol KW - GEB06NHM23 KW - Index Medicus KW - Rats KW - Protein Kinase C -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - Aorta, Thoracic -- drug effects KW - Aorta, Thoracic -- metabolism KW - In Vitro Techniques KW - Enzyme Activation -- drug effects KW - Male KW - Hypertension -- chemically induced KW - Thromboxane A2 -- metabolism KW - Hypertension -- prevention & control KW - Immunosuppressive Agents -- toxicity KW - Nitric Oxide -- metabolism KW - Metoprolol -- pharmacology KW - Cyclosporine -- toxicity KW - Adrenergic beta-Antagonists -- pharmacology KW - Hypertension -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73036968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=Role+of+metoprolol%2C+B1-adrenoceptor+antagonist%2C+thromboxane+A2+and+nitric+oxide+in+CsA-induced+hypertension.&rft.au=Oriji%2C+Gibson+K&rft.aulast=Oriji&rft.aufirst=Gibson&rft.date=2003-03-01&rft.volume=68&rft.issue=3&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-09-11 N1 - Date created - 2003-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Myoclonic epilepsy in Gaucher disease: genotype-phenotype insights from a rare patient subgroup. AN - 73036500; 12595585 AB - Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, presents with a wide spectrum of manifestations. Although Gaucher disease has been divided into three clinical types, patients with atypical presentations continue to be recognized. A careful phenotypic and genotypic assessment of patients with unusual symptoms may help define factors that modify phenotype in this disorder. One such example is a rare subgroup of patients with type 3 Gaucher disease who develop progressive myoclonic epilepsy. We evaluated 16 patients with myoclonic epilepsy, nine of whom were diagnosed by age 4 y with severe visceral involvement and myoclonus, and seven with a more chronic course, who were studied between ages 22 and 40. All of the patients had abnormal horizontal saccadic eye movements. Fourteen different genotypes were encountered, yet there were several shared alleles, including V394L (seen on two alleles), G377S (seen on three alleles), and L444P, N188S, and recombinant alleles (each found on four alleles). V394L, G377S, and N188S are mutations that have previously been associated with non-neuronopathic Gaucher disease. The spectrum of genotypes differed significantly from other patients with type 3 Gaucher disease, where genotypes L444P/L444P and R463C/null allele predominated. Northern blot studies revealed a normal glucocerebrosidase transcript, whereas Western studies showed that the patients studied lacked the processed 56 kD isoform of the enzyme, consistent with neuronopathic Gaucher disease. Brain autopsy samples from two patients demonstrated elevated levels of glucosylsphingosine, a toxic glycolipid, which could contribute to the development of myoclonus. Thus, although there were certain shared mutant alleles found in these patients, both the lack of a shared genotype and the variability in clinical presentations suggest that other modifiers must contribute to this rare phenotype. JF - Pediatric research AU - Park, Joseph K AU - Orvisky, Eduard AU - Tayebi, Nahid AU - Kaneski, Christine AU - Lamarca, Mary E AU - Stubblefield, Barbara K AU - Martin, Brian M AU - Schiffmann, Raphael AU - Sidransky, Ellen AD - Clinical Neuroscience Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2003/03// PY - 2003 DA - March 2003 SP - 387 EP - 395 VL - 53 IS - 3 SN - 0031-3998, 0031-3998 KW - Psychosine KW - 2238-90-6 KW - sphingosyl beta-glucoside KW - 52050-17-6 KW - Glucosylceramidase KW - EC 3.2.1.45 KW - Sphingosine KW - NGZ37HRE42 KW - Index Medicus KW - DNA Mutational Analysis KW - Humans KW - Psychosine -- analogs & derivatives KW - Transcription, Genetic KW - Brain -- metabolism KW - Child KW - Child, Preschool KW - Genotype KW - Phenotype KW - Adult KW - Adolescent KW - Female KW - Male KW - Sphingosine -- metabolism KW - Gaucher Disease -- genetics KW - Glucosylceramidase -- metabolism KW - Epilepsies, Myoclonic -- genetics KW - Epilepsies, Myoclonic -- metabolism KW - Glucosylceramidase -- genetics KW - Sphingosine -- analogs & derivatives KW - Gaucher Disease -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/73036500?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatric+research&rft.atitle=Myoclonic+epilepsy+in+Gaucher+disease%3A+genotype-phenotype+insights+from+a+rare+patient+subgroup.&rft.au=Park%2C+Joseph+K%3BOrvisky%2C+Eduard%3BTayebi%2C+Nahid%3BKaneski%2C+Christine%3BLamarca%2C+Mary+E%3BStubblefield%2C+Barbara+K%3BMartin%2C+Brian+M%3BSchiffmann%2C+Raphael%3BSidransky%2C+Ellen&rft.aulast=Park&rft.aufirst=Joseph&rft.date=2003-03-01&rft.volume=53&rft.issue=3&rft.spage=387&rft.isbn=&rft.btitle=&rft.title=Pediatric+research&rft.issn=00313998&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2003-08-27 N1 - Date created - 2003-02-21 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 230800; OMIM N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Combinatorial Lead Optimization of [1,2]-Diamines Based on Ethambutol as Potential Antituberculosis Preclinical Candidates AN - 18944577; 5684993 AB - Despite relatively modest potency, ethambutol (EMB, (S,S)-[N,N-di-2-amino-1-butanol]ethylenediamine) is a mainstay of contemporary chemotherapy for the treatment of tuberculosis. We have developed a solid-phase synthesis of 1,2-diamine analogues of EMB using a novel acylation-reduction sequence that is compatible with high-throughput 96-well format chemistry. Using this procedure, we have synthesized 63 238 diamine analogues in pools of 10 that are suitable for testing. MIC and a target-based reporter assay were used to direct deconvolution of 2796 individual compounds from these mixtures, and the 69 most potent molecules were resynthesized in milligram quantities for hit confirmation. Purification of these individual active diamine analogues allowed the identification of 26 compounds with activity equal to or greater than EMB. Amines which occurred most frequently in active compounds included many with large hydrophobic moieties, suggesting that optimization was perhaps selecting for the isoprenoid binding site of the arabinosyltransferase target of EMB. N-Geranyl-N'-(2-adamantyl)ethane-1,2-diamine (109), the most active of these diamines, displayed a 14-35-fold improvement in activity in vitro against Mycobacterium tuberculosis, as compared to EMB. JF - Journal of Combinatorial Chemistry AU - Lee, R E AU - Protopopova, M AU - Crooks, E AU - Slayden, R A AU - Terrot, M AU - Barry, CE III AD - Tuberculosis Research Section, NIAID, National Institutes of Health, Rockville, Maryland 20850, USA Y1 - 2003/03// PY - 2003 DA - Mar 2003 SP - 172 EP - 187 VL - 5 IS - 2 SN - 1520-4766, 1520-4766 KW - N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine KW - [1,2]-diamines KW - arabinosyltransferase KW - ethambutol KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Combinatorial chemistry KW - Chemotherapy KW - Mycobacterium tuberculosis KW - W4 330:Biopolymers & Food Biotechnology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18944577?accountid=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+Combinatorial+Chemistry&rft.atitle=Combinatorial+Lead+Optimization+of+%5B1%2C2%5D-Diamines+Based+on+Ethambutol+as+Potential+Antituberculosis+Preclinical+Candidates&rft.au=Lee%2C+R+E%3BProtopopova%2C+M%3BCrooks%2C+E%3BSlayden%2C+R+A%3BTerrot%2C+M%3BBarry%2C+CE+III&rft.aulast=Lee&rft.aufirst=R&rft.date=2003-03-01&rft.volume=5&rft.issue=2&rft.spage=172&rft.isbn=&rft.btitle=&rft.title=Journal+of+Combinatorial+Chemistry&rft.issn=15204766&rft_id=info:doi/10.1021%2Fcc020071p LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Combinatorial chemistry; Chemotherapy DO - http://dx.doi.org/10.1021/cc020071p ER - TY - JOUR T1 - Control of antimicrobial peptide synthesis by the agr quorum sensing system in Staphylococcus epidermidis: activity of the lantibiotic epidermin is regulated at the level of precursor peptide processing AN - 18785551; 5649312 AB - The accessory gene regulator (agr) quorum sensing system in staphylococci is responsible for the regulation of surface proteins and exoproteins, including many virulence factors in the pathogenic species Staphylococcus aureus and S. epidermidis. Strain S. epidermidis Tue3298 produces the lantibiotic epidermin. An isogenic agr deletion mutant of this strain showed a strong reduction of epidermin production. Detailed analysis of the impact of agr on epidermin biosynthesis revealed that agr does not interfere with the transcription of epidermin biosynthetic genes, but controls the extracellular processing of the N-terminal leader peptide by the EpiP protease. JF - Peptides AU - Kies, S AU - Vuong, C AU - Hille, M AU - Peschel, A AU - Meyer, C AU - Goetz, F AU - Otto, M AD - Mikrobielle Genetik, Universitaet Tuebingen Waldhaeuserstr. 70/8, Tuebingen 72076, Germany, motto@niaid.nih.gov Y1 - 2003/03// PY - 2003 DA - Mar 2003 SP - 329 EP - 338 VL - 24 IS - 3 SN - 0196-9781, 0196-9781 KW - agr gene KW - epidermin KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - A 01095:Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18785551?accountid=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=Peptides&rft.atitle=Control+of+antimicrobial+peptide+synthesis+by+the+agr+quorum+sensing+system+in+Staphylococcus+epidermidis%3A+activity+of+the+lantibiotic+epidermin+is+regulated+at+the+level+of+precursor+peptide+processing&rft.au=Kies%2C+S%3BVuong%2C+C%3BHille%2C+M%3BPeschel%2C+A%3BMeyer%2C+C%3BGoetz%2C+F%3BOtto%2C+M&rft.aulast=Kies&rft.aufirst=S&rft.date=2003-03-01&rft.volume=24&rft.issue=3&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Peptides&rft.issn=01969781&rft_id=info:doi/10.1016%2FS0196-9781%2803%2900046-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0196-9781(03)00046-9 ER - TY - JOUR T1 - Predictive value of clinical features in differentiating group A beta -hemolytic streptococcal pharyngitis in children AN - 18765647; 5642292 AB - Identifying children with acute pharyngitis caused by group A beta -hemolytic Streptococcus (GABHS) is an important task for pediatricians. This study examined the value of certain clinical symptoms and signs in predicting a positive culture result. A total of 442 children who presented at the outpatient department with pharyngeal erythema were enrolled. The clinical features of patients with positive throat cultures for GABHS were compared to those with negative culture results. Throat cultures were positive for GABHS in 120 (27%) patients. Patients aged between 5 and 10 years had a higher prevalence of GABHS pharyngitis. Significant differences between the groups with and without GABHS pharyngitis were noted for the presence of sore throat (p<0.001), tonsillar swelling (p<0.001), anterior cervical adenopathy (p=0.004), and scarlatiniform rash (p<0.001), but not for the presence of fever, cough, rhinorrhea, abdominal pain, headache, tonsillar exudate, or palatal petechiae. Despite these strong associations, none of these symptoms or signs had both high sensitivity and specificity, and the positive predictive values of these individual findings were never greater than 50%. The results indicate that diagnosis based on clinical grounds alone is unreliable although there are certain individual symptoms and signs that are associated with GABHS pharyngitis. These symptoms and signs may be helpful in modifying estimates of probability of infection with GABHS. Throat cultures in suspected patients remain mandatory. JF - Journal of Microbiology, Immunology and Infection AU - Lin, Meng-Hsun AU - Fong, Wen-Ki AU - Chang, Pi-Feng AU - Yen, Chih-Wei AU - Hung, Koong-Lon AU - Lin, Shwu-Jing AD - Department of Pediatrics, Cathay General Hospital-Neihu, 360, Section 2, Nei-Hu Road, Taipei, Taiwan, 114, ROC, chumeng@cgh.org.tw Y1 - 2003/03// PY - 2003 DA - Mar 2003 SP - 21 EP - 25 PB - Lippincott Willaims & Wilkins Asia Ltd. VL - 36 IS - 1 SN - 1684-1182, 1684-1182 KW - streptococci KW - throat culture KW - Microbiology Abstracts B: Bacteriology KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18765647?accountid=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+Microbiology%2C+Immunology+and+Infection&rft.atitle=Predictive+value+of+clinical+features+in+differentiating+group+A+beta+-hemolytic+streptococcal+pharyngitis+in+children&rft.au=Lin%2C+Meng-Hsun%3BFong%2C+Wen-Ki%3BChang%2C+Pi-Feng%3BYen%2C+Chih-Wei%3BHung%2C+Koong-Lon%3BLin%2C+Shwu-Jing&rft.aulast=Lin&rft.aufirst=Meng-Hsun&rft.date=2003-03-01&rft.volume=36&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Journal+of+Microbiology%2C+Immunology+and+Infection&rft.issn=16841182&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 - Parametric and non-parametric statistical analysis of DT-MRI data AN - 18756347; 5626709 AB - In this work parametric and non-parametric statistical methods are proposed to analyze Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) data. A Multivariate Normal Distribution is proposed as a parametric statistical model of diffusion tensor data when magnitude MR images contain no artifacts other than Johnson noise. We test this model using Monte Carlo (MC) simulations of DT-MRI experiments. The non-parametric approach proposed here is an implementation of bootstrap methodology that we call the DT-MRI bootstrap. It is used to estimate an empirical probability distribution of experimental DT-MRI data, and to perform hypothesis tests on them. The DT-MRI bootstrap is also used to obtain various statistics of DT-MRI parameters within a single voxel, and within a region of interest (ROI); we also use the bootstrap to study the intrinsic variability of these parameters in the ROI, independent of background noise. We evaluate the DT-MRI bootstrap using MC simulations and apply it to DT-MRI data acquired on human brain in vivo, and on a phantom with uniform diffusion properties. JF - Journal of Magnetic Resonance AU - Pajevic, S AU - Basser, P J AD - Section on Tissue Biophysics and Biomimetics, Laboratory of Integrative and Medical Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, NIH/13 South Dr./Building 13, Room 3W16, Bethesda, MD 20892-5772, USA, pajevic@nih.gov Y1 - 2003/03// PY - 2003 DA - Mar 2003 SP - 1 EP - 14 VL - 161 IS - 1 SN - 1090-7807, 1090-7807 KW - Monte Carlo simulation KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18756347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Magnetic+Resonance&rft.atitle=Parametric+and+non-parametric+statistical+analysis+of+DT-MRI+data&rft.au=Pajevic%2C+S%3BBasser%2C+P+J&rft.aulast=Pajevic&rft.aufirst=S&rft.date=2003-03-01&rft.volume=161&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Journal+of+Magnetic+Resonance&rft.issn=10907807&rft_id=info:doi/10.1016%2FS1090-7807%2802%2900178-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S1090-7807(02)00178-7 ER - TY - JOUR T1 - Characterization of an interleukin-7-dependent thymic cell line derived from a p53 super(-/-) mouse AN - 18734695; 5612910 AB - In order to study the response of T cells to IL-7, we aimed to generate an IL-7-dependent thymocyte line. CD4 super(-)CD8 super(-) thymocytes from a p53 super(-)/ super(-) mouse were continuously propagated in interleukin-7 (IL-7), and after 2 months there developed an immortal line termed 'D1.' The D1 line has retained a stable dependency on IL-7. Withdrawal of IL-7 from D1 cells induced arrest in G1 phase of the cell cycle, followed by apoptosis. In addition to IL-7, several other cytokines that employ gamma c as part of their receptor were also capable of stimulating D1 cell survival and proliferation. Gene induction by IL-7 was analyzed in D1 cells using RNase protection and array analysis and revealed a number of transcripts potentially involved in cell cycle, apoptosis and signaling. JF - Journal of Immunological Methods AU - Kim, K AU - Khaled, A R AU - Reynolds, D AU - Young, HA AU - Lee, C AU - Durum, S K AD - Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA, durums@mail.ncifcrf.gov Y1 - 2003/03/01/ PY - 2003 DA - 2003 Mar 01 SP - 177 EP - 184 PB - Elsevier Science B.V. VL - 274 IS - 1-2 SN - 0022-1759, 0022-1759 KW - mice KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - F 067735:Interleukins KW - W3 33235:New cell lines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18734695?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=unknown&rft.jtitle=Vaccine+Weekly&rft.atitle=Plague+Vaccine%3B+Novel+vaccine+candidates+against+Yersinia+pestis+generated&rft.au=&rft.aulast=&rft.aufirst=&rft.date=2004-04-28&rft.volume=&rft.issue=&rft.spage=52&rft.isbn=&rft.btitle=&rft.title=Vaccine+Weekly&rft.issn=10742921&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0022-1759(02)00513-6 ER - TY - JOUR T1 - Heterogeneity of cag Genotypes in Helicobacter pylori Isolates from Human Biopsy Specimens AN - 18693919; 5588525 AB - The Helicobacter pylori chromosomal cluster of genes known as the cytotoxin-associated gene (cag) island may have different compositions in infecting strains. In this study, we analyzed 150 single colonies obtained from gastric biopsy specimens from 10 patients infected with cagA-positive H. pylori strains and sweep isolates (isolates harvested with sweep in different points of the plate) from 6 patients infected with cagA-negative strains. Three loci in the cag island (cagA, cagE, and virB11) and the conserved gene glmM (ureC) were investigated by PCR. The levels of anti-H. pylori and anti-CagA antibodies in patient sera were also measured. For subjects infected with cagA-negative strains, all sweep isolates were also negative for cagE and virB11, suggesting the complete absence of the cag island. For subjects infected with cagA-positive strains, most of the isolates were positive for all three genes studied, whereas 24.7% of the isolates had a partial or total deletion of the cag island. cagA, cagE, and virB11 were, respectively, present in 87.3, 77.3, and 90% of the colonies. The deletion of virB11 was always associated with the deletion of cagA and/or cagE. H. pylori colonies with different cag genotypes were isolated within a single gastric biopsy specimen from 3 of the 10 patients and were further characterized by random amplified polymorphic DNA (RAPD) analysis and by sequencing of an arbitrarily selected gene segment. Although the colonies had different cag genotypes, their RAPD profiles were highly similar within each patient, and the nucleotide sequences of the selected gene segment were identical. All of the patients had detectable antibodies against H. pylori, and 9 of 10 had anti-CagA antibodies. In conclusion, we show that a single infecting H. pylori strain may include variable proportions of colony subtypes with different cag genotypes. The extension of our analysis to patients with well- characterized gastric diseases may provide significant information on the relationship between cag genotypes and clinical outcomes of H. pylori infections. JF - Journal of Clinical Microbiology AU - Tomasini, M L AU - Zanussi, S AU - Sozzi, M AU - Tedeschi, R AU - Basaglia, G AU - De Paoli, P AD - Division of Gastroenterology and Digestive Endoscopy, Centro Di Riferimento Oncologico-National Cancer Institute, Via Pedemontana Occidentale 12, 33081 Aviano (Pordenone), Italy, msozzi@cro.it Y1 - 2003/03// PY - 2003 DA - Mar 2003 SP - 976 EP - 980 VL - 41 IS - 3 SN - 0095-1137, 0095-1137 KW - cagA gene KW - cagE gene KW - glmM gene KW - heterogeneity KW - virB11 gene KW - Microbiology Abstracts B: Bacteriology KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18693919?accountid=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=Heterogeneity+of+cag+Genotypes+in+Helicobacter+pylori+Isolates+from+Human+Biopsy+Specimens&rft.au=Tomasini%2C+M+L%3BZanussi%2C+S%3BSozzi%2C+M%3BTedeschi%2C+R%3BBasaglia%2C+G%3BDe+Paoli%2C+P&rft.aulast=Tomasini&rft.aufirst=M&rft.date=2003-03-01&rft.volume=41&rft.issue=3&rft.spage=976&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/10.1128%2FJCM.41.3.976-980.2003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1128/JCM.41.3.976-980.2003 ER - TY - JOUR T1 - The next ice age: cryo-electron tomography of intact cells AN - 17816510; 5627505 AB - Recent advances in electron tomography are beginning to reveal the internal structure of eukaryotic cells in their native states in three dimensions at molecular resolution. These observations represent the culmination of years of effort to develop protocols for automated data collection, image reconstruction and cryogenic preservation. Cryo-tomograms of Dictyostelium cells depict distinct populations of ribosomes, proteasomes and networks of actin filaments interconnected by branching or bundling, apparently controlled by strategically placed actin-associated proteins. JF - Trends in Cell Biology AU - Steven, A C AU - Aebi, U AD - Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA, alasdair_steven@nih.gov Y1 - 2003/03// PY - 2003 DA - Mar 2003 SP - 107 EP - 110 VL - 13 IS - 3 SN - 0962-8924, 0962-8924 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Reviews KW - proteasomes KW - Tomography KW - Ribosomes KW - Actin KW - Data collections KW - Filaments KW - Cryogenics KW - Dictyostelium KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17816510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Cell+Biology&rft.atitle=The+next+ice+age%3A+cryo-electron+tomography+of+intact+cells&rft.au=Steven%2C+A+C%3BAebi%2C+U&rft.aulast=Steven&rft.aufirst=A&rft.date=2003-03-01&rft.volume=13&rft.issue=3&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Trends+in+Cell+Biology&rft.issn=09628924&rft_id=info:doi/10.1016%2FS0962-8924%2803%2900023-0 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dictyostelium; Tomography; Actin; Reviews; Ribosomes; Filaments; proteasomes; Cryogenics; Data collections DO - http://dx.doi.org/10.1016/S0962-8924(03)00023-0 ER - TY - JOUR T1 - Multidrug-resistant Corynebacterium striatum pneumonia in a heart transplant recipient AN - 17121202; 6593689 AB - Corynebacterium striatum is a rare, but likely underreported, cause of serious infections in immunocompromised hosts and generally is susceptible to multiple classes of antimicrobial agents. Here we report the first case of C. striatum infection in a solid organ transplant recipient. Three years after heart transplantation, a 58-year-old man developed bilateral pneumonia and pulmonary embolism. He did not improve with levofloxacin, piperacillin-tazobactam, and heparin treatment. A homogeneous population of abundant gram-positive rods was repeatedly demonstrated in sputum and bronchoalveolar lavage fluid, and C. striatum was grown in pure culture. The isolate was unusual for its multidrug-resistant (MDR) antimicrobial susceptibility pattern. The pneumonia resolved with 4 weeks of vancomycin therapy, in combination with rifampin given only during the first 2 weeks of treatment. The isolation of coryneforms ('diphtheroids') is often attributed to contamination. Their abundant presence on direct examination of specimens and-or their growth in pure culture suggest a pathogenic role, however, and indicate the need for accurate microbiological identification, particularly in immunocompromised hosts who have been hospitalized and previously treated with antibiotics. Combination therapy that includes vancomycin may be the most prudent treatment for MDR C. striatum infections. JF - Transplant Infectious Disease AU - Tarr, P E AU - Stock, F AU - Cooke, R H AU - Fedorko, D P AU - Lucey AD - Section of Infectious Diseases, Department of Medicine, Washington Hospital Center, Washington, DC 20010, USA, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA, philiptarr@yahoo.com Y1 - 2003/03// PY - 2003 DA - Mar 2003 SP - 53 EP - 58 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 5 IS - 1 SN - 1398-2273, 1398-2273 KW - Microbiology Abstracts B: Bacteriology KW - piperacillin-tazobactam KW - Pure culture KW - Coryneforms KW - Contamination KW - Levofloxacin KW - Diphtheroids KW - Antibiotics KW - Alveoli KW - Antimicrobial agents KW - Rifampin KW - Bronchus KW - Embolism KW - Corynebacterium striatum KW - Immunocompromised hosts KW - Vancomycin KW - Multidrug resistance KW - Sputum KW - Heparin KW - Pneumonia KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17121202?accountid=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=Transplant+Infectious+Disease&rft.atitle=Multidrug-resistant+Corynebacterium+striatum+pneumonia+in+a+heart+transplant+recipient&rft.au=Tarr%2C+P+E%3BStock%2C+F%3BCooke%2C+R+H%3BFedorko%2C+D+P%3BLucey&rft.aulast=Tarr&rft.aufirst=P&rft.date=2003-03-01&rft.volume=5&rft.issue=1&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Transplant+Infectious+Disease&rft.issn=13982273&rft_id=info:doi/10.1034%2Fj.1399-3062.2003.00002.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - SuppNotes - Figures, 2; references, 20. N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Pure culture; piperacillin-tazobactam; Coryneforms; Contamination; Levofloxacin; Antibiotics; Diphtheroids; Alveoli; Antimicrobial agents; Rifampin; Bronchus; Embolism; Immunocompromised hosts; Vancomycin; Multidrug resistance; Sputum; Heparin; Pneumonia; Corynebacterium striatum DO - http://dx.doi.org/10.1034/j.1399-3062.2003.00002.x ER - TY - JOUR T1 - Crystallin genes: specialization by changes in gene regulation may precede gene duplication AN - 1034820895; 17027053 AB - The crystallins account for 80-90% of the water-soluble proteins of the transparent lens. These diverse proteins are responsible for the optical properties of the lens and have been recruited from metabolic enzymes and stress proteins. They often differ among species (i.e. are taxon-specific) and may be expressed outside of the lens where they have non-refractive roles (a situation we call gene sharing). Crystallin recruitment has occurred by changes in gene regulation resulting in high lens expression. Duck lactate dehydrogenase/-crystallin and alpha -enolase/ tau -crystallin are each encoded in single-copy genes, consistent with these enzymes acquiring a crystallin role, without loss of their nonlens metabolic function, by a change in gene regulation in the absence of gene duplication. The small heat shock protein/ alpha -crystallins and avian argininosuccinate lyase/ delta -crystallins were also recruited by a change in gene regulation leading to high lens expression, except this was followed by a gene duplication with further lens specialization of the alpha A and the delta 1 (in chickens) crystallin genes. Cephalopod (squid and octopus) S-crystallins were recruited from glutathione S-transferase apparently after duplication of the original gene encoding the enzyme, although this remains uncertain. We speculate that one of the new genes (glutathione S-transferase/S11-crystallin) specialized for lens expression by a change in gene regulation and subsequently duplicated many times to form the lens-specialized, multiple S-crystallins that lack enzymatic activity. That similar transcription factors (e.g. Pax-6, retinoic acid receptors, maf, Sox, AP-1, CREB) regulate different crystallin genes suggest that common features of lens-specific expression have played a pivotal role for recruiting the diverse, multifunctional proteins as crystallins. JF - Journal of Structural and Functional Genomics AU - Piatigorsky, Joram AD - Laboratory of Molecular and Developmental Biology, National Eye Institute, NIH, Bethesda, Maryland, 20892-2730, USA Y1 - 2003/03// PY - 2003 DA - Mar 2003 SP - 131 EP - 137 PB - Springer Science+Business Media, Van Godewijckstraat 30 Dordrecht 3311 GX Netherlands VL - 3 IS - 1-4 SN - 1345-711X, 1345-711X KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts KW - Activator protein 1 KW - Argininosuccinate lyase KW - Crystallin KW - Cyclic AMP response element-binding protein KW - Enzymatic activity KW - Gene regulation KW - Glutathione transferase KW - L-Lactate dehydrogenase KW - Optical properties KW - Recruitment KW - Retinoic acid receptors KW - Specialization KW - Structure-function relationships KW - Transcription KW - Transcription factors KW - alpha -Crystallin KW - small heat shock proteins KW - stress proteins KW - Octopus KW - W 30940:Products KW - G 07730:Development & Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1034820895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Structural+and+Functional+Genomics&rft.atitle=Crystallin+genes%3A+specialization+by+changes+in+gene+regulation+may+precede+gene+duplication&rft.au=Piatigorsky%2C+Joram&rft.aulast=Piatigorsky&rft.aufirst=Joram&rft.date=2003-03-01&rft.volume=3&rft.issue=1-4&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Journal+of+Structural+and+Functional+Genomics&rft.issn=1345711X&rft_id=info:doi/10.1023%2FA%3A1022626304097 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-08-01 N1 - Last updated - 2012-09-10 N1 - SubjectsTermNotLitGenreText - Crystallin; Retinoic acid receptors; small heat shock proteins; Optical properties; Activator protein 1; Recruitment; stress proteins; Transcription; Specialization; Argininosuccinate lyase; Glutathione transferase; alpha -Crystallin; L-Lactate dehydrogenase; Structure-function relationships; Gene regulation; Transcription factors; Enzymatic activity; Cyclic AMP response element-binding protein; Octopus DO - http://dx.doi.org/10.1023/A:1022626304097 ER -