TY - JOUR T1 - Metabotropic glutamate receptors and dopamine receptors cooperate to enhance extracellular signal-regulated kinase phosphorylation in striatal neurons. AN - 67743234; 15829628 AB - Striatal medium spiny neurons are an important site of convergence for signaling mediated by the neurotransmitters dopamine and glutamate. We report that in striatal neurons in primary culture, signaling through group I metabotropic glutamate receptors (mGluRs) 1/5 and the D1 class of dopamine receptors (DRs) 1/5 converges to increase phosphorylation of the mitogen-activated protein kinase ERK2 (extracellular signal-regulated kinase 2). Induction of mitogen-activated protein kinase kinase-dependent signaling cascades by either mGluR1/5 or DR1/5 gave rise to increases in phosphorylation of ERK2. Coactivation of mGluR1/5 and DR1/5 with (S)-3,5-dihydroxyphenylglycine and (+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride enhanced the phosphorylation of ERK2. This interaction between mGluR1/5 and DR1/5 required protein kinase C (PKC), because the PKC inhibitors calphostin C, bisindolylmaleimide I, and Gö6976 blocked DR1/5-enhanced phosphorylation of ERK2. Use of the phosphatase inhibitors calyculin and okadaic acid indicated that inhibition of protein phosphatases 1 and 2A dramatically enhanced ERK2 phosphorylation by mGluR1/5. Coactivation of mGluR1/5 and DR1/5 also enhanced cAMP-response element binding protein (CREB) phosphorylation (compared with each receptor agonist alone) but did not enhance CREB-mediated transcriptional activity. Thus, signal transduction pathways activated by DR1/5 and mGluR5 interact to modify downstream events in striatal neurons while retaining numerous regulatory checkpoints. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Voulalas, Pamela J AU - Holtzclaw, Lynne AU - Wolstenholme, Jennifer AU - Russell, James T AU - Hyman, Steven E AD - Molecular Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. pvoul001@umaryland.edu Y1 - 2005/04/13/ PY - 2005 DA - 2005 Apr 13 SP - 3763 EP - 3773 VL - 25 IS - 15 KW - 2-chloro-5-hydroxyphenylglycine KW - 0 KW - Benzazepines KW - Benzoates KW - Dicarboxylic Acids KW - Dopamine Agonists KW - Dopamine Antagonists KW - Enzyme Inhibitors KW - Excitatory Amino Acid Agonists KW - Excitatory Amino Acid Antagonists KW - Phenylacetates KW - Receptors, Dopamine D1 KW - Receptors, Metabotropic Glutamate KW - metabotropic glutamate receptor type 1 KW - alpha-methyl-4-carboxyphenylglycine KW - 146669-29-6 KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - dihydroxyphenylethylene glycol KW - CF5G2G268A KW - Protein Kinase C KW - EC 2.7.11.13 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Calcium KW - SY7Q814VUP KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Animals KW - Drug Interactions KW - Benzazepines -- pharmacology KW - Analysis of Variance KW - Phenylacetates -- pharmacology KW - Dopamine Antagonists -- pharmacology KW - Dicarboxylic Acids -- pharmacology KW - Methoxyhydroxyphenylglycol -- analogs & derivatives KW - Glycine -- analogs & derivatives KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology KW - Models, Biological KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Rats KW - Calcium -- metabolism KW - Phosphorylation KW - Dopamine Agonists -- pharmacology KW - Glycine -- pharmacology KW - Excitatory Amino Acid Agonists -- pharmacology KW - Protein Kinase C -- pharmacology KW - Embryo, Mammalian KW - Fluorescent Antibody Technique KW - Benzoates -- pharmacology KW - Pregnancy KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Transfection KW - Cells, Cultured KW - Enzyme Inhibitors -- pharmacology KW - Methoxyhydroxyphenylglycol -- pharmacology KW - Female KW - Corpus Striatum -- cytology KW - Neurons -- metabolism KW - Receptors, Dopamine D1 -- physiology KW - Neurons -- drug effects KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - Receptors, Metabotropic Glutamate -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67743234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Metabotropic+glutamate+receptors+and+dopamine+receptors+cooperate+to+enhance+extracellular+signal-regulated+kinase+phosphorylation+in+striatal+neurons.&rft.au=Voulalas%2C+Pamela+J%3BHoltzclaw%2C+Lynne%3BWolstenholme%2C+Jennifer%3BRussell%2C+James+T%3BHyman%2C+Steven+E&rft.aulast=Voulalas&rft.aufirst=Pamela&rft.date=2005-04-13&rft.volume=25&rft.issue=15&rft.spage=3763&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 - 2006-02-13 N1 - Date created - 2005-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Substrate specificity of the human protein phosphatase 2Cdelta, Wip1. AN - 67704863; 15807522 AB - Wip1, the wild-type p53-induced phosphatase, selectively dephosphorylates a threonine residue on p38 MAPK and mediates a negative feedback loop of the p38 MAPK-p53 signaling pathway. To identify the substrate specificity of Wip1, we prepared a recombinant human Wip1 catalytic domain (rWip1) and measured kinetic parameters for phosphopeptides containing the dephosphorylation sites in p38alpha and in a new substrate, UNG2. rWip1 showed properties that were comparable to those of PP2Calpha or full-length Wip1 in terms of affinity for Mg(2+), insensitivity to okadaic acid, and threonine dephosphorylation. The substrate specificity constant k(cat)/K(m) for a diphosphorylated peptide with a pTXpY sequence was 6-8-fold higher than that of a monophosphorylated peptide with a pTXY sequence, while PP2Calpha showed a preference for monophosphorylated peptides. Although individual side chains before and after the pTXpY sequence of the substrate did not have a significant effect on rWip1 activity, a chain length of at least five residues, including the pTXpY sequence, was important for substrate recognition by rWip1. Moreover, the X residue in the pTXpY sequence affected affinity for rWip1 and correlated with selectivity for MAPKs. These findings suggest that substrate recognition by Wip1 is centered toward a very narrow region around the pTXpY sequence. Three-dimension homology models of Wip1 with bound substrate peptides were constructed, and site-directed mutagenesis was performed to confirm the importance of specific residues for substrate recognition. The results of our study should be useful for predicting new physiological substrates and for designing specific Wip1 inhibitors. JF - Biochemistry AU - Yamaguchi, Hiroshi AU - Minopoli, Giuseppina AU - Demidov, Oleg N AU - Chatterjee, Deb K AU - Anderson, Carl W AU - Durell, Stewart R AU - Appella, Ettore AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2005/04/12/ PY - 2005 DA - 2005 Apr 12 SP - 5285 EP - 5294 VL - 44 IS - 14 SN - 0006-2960, 0006-2960 KW - DNA Primers KW - 0 KW - Enzyme Inhibitors KW - Neoplasm Proteins KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Threonine KW - 2ZD004190S KW - PPM1D protein, human KW - EC 3.1.3.16 KW - Phosphoprotein Phosphatases KW - Protein Phosphatase 2C KW - Index Medicus KW - Threonine -- metabolism KW - Humans KW - Catalytic Domain KW - Amino Acid Sequence KW - Base Sequence KW - Phosphorylation KW - Kinetics KW - Molecular Sequence Data KW - Okadaic Acid -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Phosphoprotein Phosphatases -- antagonists & inhibitors KW - Neoplasm Proteins -- antagonists & inhibitors KW - Phosphoprotein Phosphatases -- metabolism KW - Phosphoprotein Phosphatases -- chemistry KW - Neoplasm Proteins -- chemistry KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67704863?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Substrate+specificity+of+the+human+protein+phosphatase+2Cdelta%2C+Wip1.&rft.au=Yamaguchi%2C+Hiroshi%3BMinopoli%2C+Giuseppina%3BDemidov%2C+Oleg+N%3BChatterjee%2C+Deb+K%3BAnderson%2C+Carl+W%3BDurell%2C+Stewart+R%3BAppella%2C+Ettore&rft.aulast=Yamaguchi&rft.aufirst=Hiroshi&rft.date=2005-04-12&rft.volume=44&rft.issue=14&rft.spage=5285&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-07 N1 - Date created - 2005-04-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calmodulin is required for vasopressin-stimulated increase in cyclic AMP production in inner medullary collecting duct. AN - 67696052; 15710610 AB - Calmodulin plays a critical role in regulation of renal collecting duct water permeability by vasopressin. However, specific targets for calmodulin action have not been thoroughly addressed. In the present study, we investigated whether Ca2+/calmodulin regulates adenylyl cyclase activity in the renal inner medullary collecting duct. Rat inner medullary collecting duct suspensions were incubated in the presence or absence of 0.1 nM vasopressin and the calmodulin inhibitors, monodansylcadaverine, W-7, and trifluoperazine, followed by measurement of cAMP. Vasopressin-stimulated cAMP elevation was significantly attenuated in the presence of calmodulin inhibitors. Analysis of transglutaminase 2 knock-out mice confirmed that these compounds were not acting through inhibition of transglutaminase 2 activity. Calmodulin inhibitors also blocked both cholera toxin- and forskolin-stimulated cAMP accumulation. In isolated perfused tubules, W-7 reversibly blocked vasopressin-stimulated urea permeability, a process that requires a rise in intracellular cAMP but does not appear to involve protein trafficking to the apical plasma membrane. These results suggest that calmodulin is required for vasopressin-stimulated adenylyl cyclase activity in the intact inner medullary collecting duct. Reverse transcription-PCR, immunoblotting, and immunohistochemistry revealed the presence of the calmodulin-sensitive adenylyl cyclase type 3 in the rat collecting duct, an isoform previously not known to be expressed in the collecting duct. Long-term treatment of Brattleboro rats with a vasopressin analog markedly decreased adenylyl cyclase type 3 protein abundance, providing an explanation for long-term down-regulation of vasopressin response in the collecting duct. These studies demonstrate the importance of calmodulin in the regulation of collecting duct adenylyl cyclase activity and transport function. JF - The Journal of biological chemistry AU - Hoffert, Jason D AU - Chou, Chung-Lin AU - Fenton, Robert A AU - Knepper, Mark A AD - Laboratory of Kidney and Electrolyte Metabolism, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2005/04/08/ PY - 2005 DA - 2005 Apr 08 SP - 13624 EP - 13630 VL - 280 IS - 14 SN - 0021-9258, 0021-9258 KW - Calmodulin KW - 0 KW - Enzyme Inhibitors KW - Isoenzymes KW - Sulfonamides KW - Arginine Vasopressin KW - 113-79-1 KW - Colforsin KW - 1F7A44V6OU KW - Trifluoperazine KW - 214IZI85K3 KW - W 7 KW - 65595-90-6 KW - Cholera Toxin KW - 9012-63-9 KW - Cyclic AMP KW - E0399OZS9N KW - transglutaminase 2 KW - EC 2.3.2.- KW - Transglutaminases KW - EC 2.3.2.13 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - monodansylcadaverine KW - I9N81SC5HD KW - Cadaverine KW - L90BEN6OLL KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Cholera Toxin -- pharmacology KW - Adenylyl Cyclases -- metabolism KW - Isoenzymes -- metabolism KW - Mice, Knockout KW - Calcium -- metabolism KW - Rats KW - Colforsin -- pharmacology KW - Transglutaminases -- metabolism KW - Sulfonamides -- pharmacology KW - Adenylyl Cyclases -- genetics KW - Trifluoperazine -- chemistry KW - Male KW - Molecular Structure KW - Transglutaminases -- antagonists & inhibitors KW - Trifluoperazine -- pharmacology KW - Transglutaminases -- genetics KW - Enzyme Inhibitors -- chemistry KW - Mice KW - GTP-Binding Proteins -- genetics KW - Isoenzymes -- genetics KW - Brain -- enzymology KW - Rats, Sprague-Dawley KW - Sulfonamides -- chemistry KW - GTP-Binding Proteins -- antagonists & inhibitors KW - Cells, Cultured KW - GTP-Binding Proteins -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Kidney Tubules, Collecting -- metabolism KW - Calmodulin -- metabolism KW - Cadaverine -- pharmacology KW - Kidney Tubules, Collecting -- cytology KW - Kidney Medulla -- metabolism KW - Arginine Vasopressin -- metabolism KW - Kidney Tubules, Collecting -- drug effects KW - Cadaverine -- analogs & derivatives KW - Cyclic AMP -- metabolism KW - Calmodulin -- antagonists & inhibitors KW - Cadaverine -- chemistry KW - Kidney Medulla -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67696052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Calmodulin+is+required+for+vasopressin-stimulated+increase+in+cyclic+AMP+production+in+inner+medullary+collecting+duct.&rft.au=Hoffert%2C+Jason+D%3BChou%2C+Chung-Lin%3BFenton%2C+Robert+A%3BKnepper%2C+Mark+A&rft.aulast=Hoffert&rft.aufirst=Jason&rft.date=2005-04-08&rft.volume=280&rft.issue=14&rft.spage=13624&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 - 2005-06-21 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Am J Physiol. 1992 Jun;262(6 Pt 2):F957-64 [1320333] J Biol Chem. 2004 Nov 19;279(47):49026-35 [15347643] J Biol Chem. 2004 Nov 5;279(45):46969-80 [15319442] Endocrinology. 1999 Oct;140(10):4601-8 [10499516] Brain Res. 1999 May 1;826(2):253-69 [10224303] Am J Physiol Renal Physiol. 2000 Jul;279(1):F185-94 [10894801] Am J Physiol Renal Physiol. 2000 Sep;279(3):F400-16 [10966920] J Biol Chem. 2000 Nov 24;275(47):36839-46 [10973964] Mol Cell Biol. 2001 Jan;21(1):148-55 [11113189] Tohoku J Exp Med. 2001 Mar;193(3):207-20 [11315768] Am J Physiol Renal Physiol. 2002 Jan;282(1):F85-90 [11739116] Physiol Rev. 2002 Jan;82(1):205-44 [11773613] J Physiol. 2002 Feb 1;538(Pt 3):891-9 [11826172] J Gen Physiol. 2002 Jul;120(1):71-85 [12084777] Am J Physiol Renal Physiol. 2004 Jan;286(1):F170-9 [12965894] Am J Physiol Renal Physiol. 2004 Feb;286(2):F216-24 [14532164] Am J Physiol Renal Physiol. 2004 May;286(5):F979-87 [15075194] Am J Physiol. 1966 Jul;211(1):255-9 [5911047] Nature. 1970 Aug 15;227(5259):680-5 [5432063] FEBS Lett. 1979 Sep 1;105(1):95-100 [226410] Nature. 1980 Oct 30;287(5785):863-5 [7432502] J Biol Chem. 1981 Oct 10;256(19):9796-8 [7275976] Biochim Biophys Acta. 1983 Jun 2;762(3):414-9 [6133561] Biochem Biophys Res Commun. 1983 Dec 16;117(2):562-7 [6318763] J Biol Chem. 1984 Nov 10;259(21):13550-9 [6092380] Am J Physiol. 1987 Aug;253(2 Pt 2):F251-62 [3303974] J Clin Invest. 1988 Jun;81(6):1879-88 [2838523] Am J Physiol. 1988 Nov;255(5 Pt 2):F834-40 [2847548] Biochemistry. 1992 Jul 21;31(28):6492-8 [1633161] Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8774-8 [1528892] Neurosci Lett. 1992 Sep 14;144(1-2):169-73 [1436697] Am J Physiol. 1993 Aug;265(2 Pt 2):F204-13 [8396342] Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11663-7 [8265605] Biochem J. 1994 Feb 1;297 ( Pt 3):437-40 [8110177] Semin Nephrol. 1994 Jul;14(4):302-21 [7938946] Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1013-7 [7532304] Am J Physiol. 1995 Jul;269(1 Pt 2):F78-85 [7631834] Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7212-6 [7543677] C R Seances Soc Biol Fil. 1995;189(2):151-67 [8590215] J Biol Chem. 1995 Oct 13;270(41):24108-15 [7592612] Am J Physiol. 1996 Apr;270(4 Pt 2):R755-60 [8967404] Am J Physiol. 1996 Apr;270(4 Pt 2):F623-33 [8967340] J Biol Chem. 1996 Aug 9;271(32):19264-71 [8702608] Am J Physiol. 1996 Aug;271(2 Pt 2):F414-22 [8770174] J Biol Chem. 1996 Sep 27;271(39):24231-5 [8798667] J Biol Chem. 1997 Dec 5;272(49):31100-6 [9388262] FEBS Lett. 1998 Mar 13;424(3):216-20 [9539154] Neuron. 1998 Sep;21(3):495-504 [9768837] Am J Physiol. 1998 Jun;274(6 Pt 2):F1161-6 [9841509] Am J Physiol. 1999 Apr;276(4 Pt 2):F559-66 [10198415] N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Modeling spontaneous activity in the developing spinal cord using activity-dependent variations of intracellular chloride. AN - 67713294; 15814791 AB - We investigated how spontaneous activity is generated in developing, hyperexcitable networks. We focused our study on the embryonic chick spinal cord, a preparation that exhibits rhythmic discharge on multiple timescales: slow episodes (lasting minutes) and faster intraepisode cycling (approximately 1 Hz frequency). For this purpose, we developed a mean field model of a recurrent network with slow chloride dynamics and a fast depression variable. We showed that the model, in addition to providing a biophysical mechanism for the slow dynamics, was able to account for the experimentally observed activity. The model made predictions on how interval and duration of episodes are affected when changing chloride-mediated synaptic transmission or chloride flux across cell membrane. These predictions guided experiments, and the model results were compared with experimental data obtained with electrophysiological recordings. We found agreement when transmission was affected through changes in synaptic conductance and good qualitative agreement when chloride flux was varied through changes in external chloride concentration or in the rate of the Na+-K+-2Cl- cotransporter. Furthermore, the model made predictions about the time course of intracellular chloride concentration and chloride reversal potential and how these are affected by changes in synaptic conductance. Based on the comparison between modeling and experimental results, we propose that chloride dynamics could be an important mechanism in rhythm generation in the developing chick spinal cord. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Marchetti, Cristina AU - Tabak, Joel AU - Chub, Nikolai AU - O'Donovan, Michael J AU - Rinzel, John AD - Laboratory of Neural Control, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2005/04/06/ PY - 2005 DA - 2005 Apr 06 SP - 3601 EP - 3612 VL - 25 IS - 14 KW - Chlorides KW - 0 KW - Excitatory Amino Acid Antagonists KW - GABA Antagonists KW - Sodium Potassium Chloride Symporter Inhibitors KW - Bumetanide KW - 0Y2S3XUQ5H KW - 6-Cyano-7-nitroquinoxaline-2,3-dione KW - 6OTE87SCCW KW - 2-Amino-5-phosphonovalerate KW - 76726-92-6 KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Bumetanide -- pharmacology KW - Animals KW - Drug Interactions KW - Synaptic Transmission -- drug effects KW - Chick Embryo KW - 6-Cyano-7-nitroquinoxaline-2,3-dione -- pharmacology KW - Neural Inhibition -- drug effects KW - GABA Antagonists -- pharmacology KW - Neural Inhibition -- physiology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Sodium Potassium Chloride Symporter Inhibitors -- pharmacology KW - Patch-Clamp Techniques KW - 2-Amino-5-phosphonovalerate -- pharmacology KW - Nonlinear Dynamics KW - Periodicity KW - Time Factors KW - Action Potentials -- physiology KW - Intracellular Space -- drug effects KW - Neural Networks (Computer) KW - Intracellular Space -- metabolism KW - Neurons -- drug effects KW - Neurons -- physiology KW - Chlorides -- metabolism KW - Spinal Cord -- physiology KW - Spinal Cord -- embryology KW - Spinal Cord -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67713294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Modeling+spontaneous+activity+in+the+developing+spinal+cord+using+activity-dependent+variations+of+intracellular+chloride.&rft.au=Marchetti%2C+Cristina%3BTabak%2C+Joel%3BChub%2C+Nikolai%3BO%27Donovan%2C+Michael+J%3BRinzel%2C+John&rft.aulast=Marchetti&rft.aufirst=Cristina&rft.date=2005-04-06&rft.volume=25&rft.issue=14&rft.spage=3601&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 - 2006-03-01 N1 - Date created - 2005-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human brain derived neurotrophic factor (BDNF) genes, splicing patterns, and assessments of associations with substance abuse and Parkinson's Disease. AN - 67542724; 15666411 AB - Potential roles for variants in the human BDNF gene in human brain disorders are supported by findings that include: (a) influences that this trophic factor can exert on important neurons, brain regions, and neurotransmitter systems, (b) changes in BDNF expression that follow altered neuronal activity and drug treatments, and (c) linkages or associations between genetic markers in or near BDNF and human traits and disorders that include depression, schizophrenia, addictions, and Parkinson's disease. We now report assembly of more than 70 kb of BDNF genomic sequence, delineation of 7 noncoding and 1 coding human BDNF exons, elucidation of BDNF transcripts that are initiated at several alternative promoters, identification of BDNF mRNA splicing patterns, elucidation of novel sequences that could contribute to activity-dependent BDNF mRNA transcription, targeting and/or translation, elucidation of tissue-specific and brain-region-specific use of the alternative human BDNF promoters and splicing patterns, identification of single nucleotide polymorphism (SNP), and simple sequence length polymorphism (SSLP) BDNF genomic variants and identification of patterns of restricted haplotype diversity at the BDNF locus. We also identified type 2 BDNF-locus transcripts that are coded by a novel gene that is overlapped with type 1 BDNF gene and transcribed in reverse orientation with several alternative splicing isoforms. Association studies of BDNF variants reveal no associations with Parkinson's disease. Comparisons between substance abusers and controls reveal modest associations. These findings increase interest in this diverse human gene. JF - American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics AU - Liu, Qing-Rong AU - Walther, Donna AU - Drgon, Tomas AU - Polesskaya, Oxana AU - Lesnick, Timothy G AU - Strain, Kari J AU - de Andrade, Mariza AU - Bower, James H AU - Maraganore, Demetrius M AU - Uhl, George R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse-Intramural Research Program (NIDA-IRP), NIH, Department of Health and Human Services (DHHS), Baltimore, Maryland, USA. Y1 - 2005/04/05/ PY - 2005 DA - 2005 Apr 05 SP - 93 EP - 103 VL - 134B IS - 1 SN - 1552-4841, 1552-4841 KW - Brain-Derived Neurotrophic Factor KW - 0 KW - RNA, Untranslated KW - Poly A KW - 24937-83-5 KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Transcription Initiation Site KW - Polymorphism, Genetic KW - Exons KW - Humans KW - Transcription, Genetic -- genetics KW - Sequence Analysis, DNA KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Untranslated -- genetics KW - Linkage Disequilibrium KW - Genes -- genetics KW - Microsatellite Repeats KW - Base Sequence KW - Haplotypes KW - RNA -- metabolism KW - DNA -- genetics KW - Introns KW - Molecular Sequence Data KW - Poly A -- genetics KW - DNA -- chemistry KW - RNA -- genetics KW - Alternative Splicing -- genetics KW - Substance-Related Disorders -- genetics KW - Parkinson Disease -- genetics KW - Brain-Derived Neurotrophic Factor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67542724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+medical+genetics.+Part+B%2C+Neuropsychiatric+genetics+%3A+the+official+publication+of+the+International+Society+of+Psychiatric+Genetics&rft.atitle=Human+brain+derived+neurotrophic+factor+%28BDNF%29+genes%2C+splicing+patterns%2C+and+assessments+of+associations+with+substance+abuse+and+Parkinson%27s+Disease.&rft.au=Liu%2C+Qing-Rong%3BWalther%2C+Donna%3BDrgon%2C+Tomas%3BPolesskaya%2C+Oxana%3BLesnick%2C+Timothy+G%3BStrain%2C+Kari+J%3Bde+Andrade%2C+Mariza%3BBower%2C+James+H%3BMaraganore%2C+Demetrius+M%3BUhl%2C+George+R&rft.aulast=Liu&rft.aufirst=Qing-Rong&rft.date=2005-04-05&rft.volume=134B&rft.issue=1&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=American+journal+of+medical+genetics.+Part+B%2C+Neuropsychiatric+genetics+%3A+the+official+publication+of+the+International+Society+of+Psychiatric+Genetics&rft.issn=15524841&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-09 N1 - Date created - 2005-03-24 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AY054399; GENBANK; AY054397; AY054398; AY054395; AY054396; AY054403; AY054393; AY054404; AY054394; AY054405; AF411339; AY054391; AY054406; AY054392; AY054402; AY054401; AY054400; AY513486 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Borrelia burgdorferi sigma super(54) is required for mammalian infection and vector transmission but not for tick colonization AN - 17635544; 6267592 AB - Previous studies have shown that a sigma super(54)- sigma super(S) cascade regulates the expression of a few key lipoproteins in Borrelia burgdorferi, the agent of Lyme disease. Here, we demonstrate that these sigma factors, both together and independently, regulate a much more extensive number of genes and cellular processes. Microarray analyses of sigma super(54) and sigma super(S) mutant strains identified 305 genes regulated by sigma super(54) and 145 regulated by sigma super(S) sub(,) whereas the sigma super(54)- sigma super(S) regulatory cascade appears to control 48 genes in B. burgdorferi. In silico analyses revealed that nearly 80% of genes with altered expression in the sigma super(54) mutant were linked to potential sigma super(54)-dependent promoters. Many sigma super(54)-regulated genes are expressed in vivo, and through genetic complementation of the mutant, we demonstrated that sigma super(54) was required by B. burgdorferi to infect mammals. Surprisingly, sigma super(54) mutants were able to infect Ixodes scapularis ticks and be maintained for at least 24 wk after infection, suggesting the sigma super(54)- sigma super(S) regulatory network was not involved in long-term survival in ticks. However, sigma super(54) mutants did not enter the salivary glands during tick feeding, indicating that sigma super(54)-regulated genes were involved in the transmission process. JF - Proceedings of the National Academy of Sciences, USA AU - Fisher, Mark A AU - Grimm, Dorothee AU - Henion, Amy K AU - Elias, Abdallah F AU - Stewart, Philip E AU - Rosa, Patricia A AU - Gherardini, Frank C AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840 Y1 - 2005/04/05/ PY - 2005 DA - 2005 Apr 05 SP - 5162 EP - 5167 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 102 IS - 14 SN - 0027-8424, 0027-8424 KW - Deer tick KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Entomology Abstracts KW - J 02726:RNA and ribosomes KW - G 07366:Insects/arachnids KW - Z 05212:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17635544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+burgdorferi+sigma+super%2854%29+is+required+for+mammalian+infection+and+vector+transmission+but+not+for+tick+colonization&rft.au=Fisher%2C+Mark+A%3BGrimm%2C+Dorothee%3BHenion%2C+Amy+K%3BElias%2C+Abdallah+F%3BStewart%2C+Philip+E%3BRosa%2C+Patricia+A%3BGherardini%2C+Frank+C&rft.aulast=Fisher&rft.aufirst=Mark&rft.date=2005-04-05&rft.volume=102&rft.issue=14&rft.spage=5162&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-09-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Protective effects of Delta(9)-tetrahydrocannabinol against N-methyl-d-aspartate-induced AF5 cell death. AN - 67752337; 15836919 AB - The neuroprotective effects of Delta(9)-tetrahydrocannabinol (THC) were examined using an in vitro model in which the AF5 CNS cell line was exposed to toxic levels of N-methyl-d-aspartate (NMDA), an agonist of the NMDA glutamate receptor. NMDA toxicity was reduced by THC, but not by the more specific cannabinoid receptor agonist, WIN55,212-2. Addition of dibutyryl cAMP (dbcAMP) to the culture medium did not alter the neuroprotective effect of THC and did not unmask a neuroprotective effect of WIN55,212-2. The cannabinoid antagonist SR141716A did not inhibit the neuroprotection induced by THC or alter the response to WIN55,212-2, even in the presence of dbcAMP, indicating that the neuroprotective effect of THC was cannabinoid receptor-independent. On the other hand, both THC and WIN55,212-2 produced cellular toxicology at higher dosages, an effect which was blocked in part by SR141716A. Capsaicin, an antioxidant and vanilloid receptor agonist, also produced a protective effect against NMDA toxicology. The protective effect of capsaicin was blocked by co-application of ruthenium red, but was not blocked by the specific vanilloid receptor antagonist capsazepine, and the transient receptor potential vanilloid type 1 (TRPV1) and ANKTM1 transcripts were not detected in AF5 cells. Thus, the neuroprotective effects of THC and capsaicin did not appear to be mediated by TRP ion channel family receptors. The antioxidant alpha-tocopherol prevented neurotoxicity in a dose-dependent manner. Therefore, THC may function as an antioxidant to increase cell survival in NMDA-induced neurotoxicity in the AF5 cell model, while higher dosages produce toxicity mediated by CB1 receptor stimulation. JF - Brain research. Molecular brain research AU - Chen, Jia AU - Lee, Chun-Ting AU - Errico, Stacie AU - Deng, Xiaolin AU - Cadet, Jean L AU - Freed, William J AD - Cellular Neurobiology Research Branch, Intramural Research Program, NIDA, National Institutes of Health, Baltimore, MD 21224, USA. jchen@intra.nida.nih.gov Y1 - 2005/04/04/ PY - 2005 DA - 2005 Apr 04 SP - 215 EP - 225 VL - 134 IS - 2 SN - 0169-328X, 0169-328X KW - Benzimidazoles KW - 0 KW - Benzoxazines KW - Calcium Channel Blockers KW - Calcium Channels KW - DNA, Single-Stranded KW - Excitatory Amino Acid Agonists KW - Morpholines KW - Naphthalenes KW - Neuroprotective Agents KW - Piperidines KW - Pyrazoles KW - RNA, Messenger KW - Receptor, Cannabinoid, CB1 KW - Receptors, N-Methyl-D-Aspartate KW - TRPC Cation Channels KW - Tetrazolium Salts KW - Thiazoles KW - Win 55212-2 KW - 5H31GI9502 KW - N-Methylaspartate KW - 6384-92-5 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Dronabinol KW - 7J8897W37S KW - Ruthenium KW - 7UI0TKC3U5 KW - thiazolyl blue KW - EUY85H477I KW - alpha-Tocopherol KW - H4N855PNZ1 KW - capsazepine KW - LFW48MY844 KW - bisbenzimide ethoxide trihydrochloride KW - P976261J69 KW - rimonabant KW - RML78EN3XE KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Naphthalenes -- pharmacology KW - Animals KW - Calcium Channels -- metabolism KW - Drug Interactions KW - Cell Lineage KW - Receptor, Cannabinoid, CB1 -- antagonists & inhibitors KW - Receptor, Cannabinoid, CB1 -- genetics KW - Receptor, Cannabinoid, CB1 -- metabolism KW - Calcium Channels -- genetics KW - RNA, Messenger -- biosynthesis KW - Dizocilpine Maleate -- pharmacology KW - Rats KW - Calcium Channel Blockers -- pharmacology KW - Blotting, Northern -- methods KW - DNA, Single-Stranded -- metabolism KW - Cell Count KW - Dose-Response Relationship, Drug KW - Ruthenium -- pharmacology KW - Morpholines -- pharmacology KW - Immunohistochemistry -- methods KW - Reverse Transcriptase Polymerase Chain Reaction -- methods KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - Cell Death -- drug effects KW - In Situ Nick-End Labeling -- methods KW - Piperidines -- pharmacology KW - Benzimidazoles -- metabolism KW - Pyrazoles -- pharmacology KW - alpha-Tocopherol -- pharmacology KW - Blotting, Western KW - Receptors, N-Methyl-D-Aspartate -- genetics KW - Neurons -- drug effects KW - Dronabinol -- pharmacology KW - Neurons -- cytology KW - N-Methylaspartate -- toxicity KW - Excitatory Amino Acid Agonists -- toxicity KW - Capsaicin -- analogs & derivatives KW - Neuroprotective Agents -- pharmacology KW - Capsaicin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67752337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Protective+effects+of+Delta%289%29-tetrahydrocannabinol+against+N-methyl-d-aspartate-induced+AF5+cell+death.&rft.au=Chen%2C+Jia%3BLee%2C+Chun-Ting%3BErrico%2C+Stacie%3BDeng%2C+Xiaolin%3BCadet%2C+Jean+L%3BFreed%2C+William+J&rft.aulast=Chen&rft.aufirst=Jia&rft.date=2005-04-04&rft.volume=134&rft.issue=2&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-05 N1 - Date created - 2005-04-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Pharmacol Rev. 2002 Jun;54(2):161-202 [12037135] Neuroscience. 2002;112(3):707-16 [12074912] J Neurochem. 2002 Jul;82(1):154-8 [12091476] Biochim Biophys Acta. 2002 Oct 10;1573(1):84-92 [12383946] Mol Neurobiol. 2002 Oct-Dec;26(2-3):317-46 [12428763] Chem Phys Lipids. 2002 Dec 31;121(1-2):257-66 [12505705] Cell. 2003 Mar 21;112(6):819-29 [12654248] J Neurosci. 2003 May 15;23(10):4127-33 [12764100] J Nat Prod. 2003 Aug;66(8):1094-6 [12932131] Am J Pathol. 2003 Nov;163(5):1997-2008 [14578199] Nature. 2004 Jan 15;427(6971):260-5 [14712238] Med Hypotheses. 2004;63(2):187-92 [15236773] Biochem Biophys Res Commun. 1971 Jan 22;42(2):298-305 [4250976] Biochim Biophys Acta. 1971 Dec 3;249(2):606-10 [4257327] J Neurosci. 1991 Aug;11(8):2545-51 [1678427] J Neurosci Res. 1993 Aug 15;35(6):585-602 [8411264] J Pharmacol Exp Ther. 1995 May;273(2):940-7 [7538585] Exp Cell Res. 1996 Aug 1;226(2):387-97 [8806443] Gen Pharmacol. 1993 Jul;24(4):811-24 [8224735] Cell Tissue Res. 1998 Feb;291(2):175-89 [9426306] J Neurosci. 1998 Jul 15;18(14):5322-32 [9651215] Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8268-73 [9653176] Mol Pharmacol. 1998 Sep;54(3):459-62 [9730904] J Neurosci. 1999 Apr 15;19(8):2987-95 [10191316] J Agric Food Chem. 1999 Jul;47(7):2563-70 [10552527] Ann N Y Acad Sci. 2000;899:274-82 [10863546] J Pharmacol Exp Ther. 2000 Jun;293(3):807-12 [10869379] J Mol Med (Berl). 2001;78(11):613-25 [11269508] Eur J Neurosci. 2001 Apr;13(8):1529-36 [11328347] J Neurosci. 2001 Sep 1;21(17):6475-9 [11517236] J Neurochem. 2002 Feb;80(3):448-56 [11905991] Trends Pharmacol Sci. 2002 Apr;23(4):183-91 [11931994] J Neurosci. 2002 Jun 1;22(11):4720-7 [12040079] Exp Neurol. 2002 Jun;175(2):318-37 [12061863] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Green tea consumption, genetic susceptibility, PAH-rich smoky coal, and the risk of lung cancer AN - 17537543; 6390986 AB - Experimental evidence suggests that green tea (Camellia sinesis) may reduce the risk of lung cancer through several hypothesized mechanisms including scavenging oxidative radicals, inhibition of tumor initiation, and modulation of detoxification enzymes. However, epidemiologic results have not been consistent as to the relationship between green tea consumption and lung caner prevention. We employed a population-based case-control study of 122 cases and 122 controls to investigate the effect that green tea consumption may have on the risk of lung cancer and whether polymorphisms in 8-oxoguanine-DNA glycosylase (OGG1), glutathione-S-transferase M1 (GSTM1), and aldo-keto reductase 1C3 (AKR1C3) modify such an association. Daily green tea consumption was associated with a non-significant reduction in lung cancer risk. However, the effect of smoky coal exposure was higher for non-drinkers (odds ratio (OR)=4.93; 95% confidence interval (95% CI)=1.27-19.13) than for drinkers (OR=1.88; 95% CI=1.01-3.48). Further, among individuals with the OGG1 Cys super(3) super(2) super(6) allele, daily consumption was associated with a 72% reduction (95% CI=0.09-0.94). Among GSTM1 null homozygotes, those who consumed green tea daily had a non-significant reduction in risk compared with non-consumers. Green tea consumption had no effect among OGG1 Ser super(3) super(2) super(6) homozygotes or GSTM1 carriers. In addition, AKR1C3 genotype did not modulate the effect of green tea consumption. The chemopreventive effects of green tea in this population may be restricted to individuals who are particularly susceptible to oxidative stress and oxidative DNA damage. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Bonner, M R AU - Rothman, N AU - Mumford, J L AU - He, X AU - Shen, M AU - Welch, R AU - Yeager, M AU - Chanock, S AU - Caporaso, N AU - Lan, Q AD - Occupational and Environmental Epidemiology Branch, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd., EPS 8121, MSC 7240, Bethesda, MD 20892-7240, USA, bonnerm@mail.nih.gov Y1 - 2005/04/04/ PY - 2005 DA - 2005 Apr 04 SP - 53 EP - 60 PB - Elsevier B.V. VL - 582 IS - 1-2 SN - 1383-5718, 1383-5718 KW - Genetics Abstracts; Risk Abstracts; Toxicology Abstracts KW - Detoxification KW - Coal KW - Risk reduction KW - Glutathione transferase KW - Nutrition KW - Homozygotes KW - Mutagenesis KW - Oxidative stress KW - aldo-keto reductase KW - Lung cancer KW - Diets KW - green tea KW - Enzymes KW - DNA damage KW - Camellia sinesis KW - Camellia KW - Radicals KW - X 24190:Polycyclic hydrocarbons KW - R2 23060:Medical and environmental health KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17537543?accountid=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=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=Green+tea+consumption%2C+genetic+susceptibility%2C+PAH-rich+smoky+coal%2C+and+the+risk+of+lung+cancer&rft.au=Bonner%2C+M+R%3BRothman%2C+N%3BMumford%2C+J+L%3BHe%2C+X%3BShen%2C+M%3BWelch%2C+R%3BYeager%2C+M%3BChanock%2C+S%3BCaporaso%2C+N%3BLan%2C+Q&rft.aulast=Bonner&rft.aufirst=M&rft.date=2005-04-04&rft.volume=582&rft.issue=1-2&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&rft_id=info:doi/10.1016%2Fj.mrgentox.2004.12.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Camellia; Camellia sinesis; Diets; Enzymes; Detoxification; Nutrition; Risk reduction; Lung cancer; green tea; Coal; Homozygotes; DNA damage; aldo-keto reductase; Glutathione transferase; Radicals; Oxidative stress; Mutagenesis DO - http://dx.doi.org/10.1016/j.mrgentox.2004.12.008 ER - TY - JOUR T1 - Suppression of thyroarytenoid muscle responses during repeated air pressure stimulation of the laryngeal mucosa in awake humans. AN - 85383300; pmid-15895780 AB - Repeated stimulation of the laryngeal mucosa occurs during speech. Single stimuli, however, can elicit the laryngeal adductor response (LAR). Our hypothesis was that the LAR to repeated rapid air pressure stimuli is centrally suppressed in humans. Hooked-wire electrodes were inserted into the thyroarytenoid and cricothyroid muscles on both sides and into the posterior cricoarytenoid muscle on one side. Pairs of air puff stimuli were presented to the mucosa over the arytenoids at pressure levels three times threshold with interstimulus intervals from 250 to 5,000 ms. Bilateral thyroarytenoid responses occurred at around 150 ms to more than 70% of the initial stimuli. With repeated presentation at intervals of 2 seconds or less, the percent occurrence decreased to less than 40% and response amplitudes were reduced by 50%. Central suppression of adductor responses to repeated air puff stimuli may allow speakers to produce voice without eliciting reflexive spasms that could disrupt speech. JF - The Annals of otology, rhinology, and laryngology AU - Kearney, Pamela Reed AU - Poletto, Christopher J AU - Mann, Eric A AU - Ludlow, Christy L AD - Laryngeal and Speech Section, National Institute of Neurological Disorders and Stroke, Building 10, Room 5D38, Bethesda, MD 20892, USA. Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 264 EP - 270 VL - 114 IS - 4 SN - 0003-4894, 0003-4894 KW - National Library of Medicine KW - Adult KW - Aged KW - Air Movements KW - Analysis of Variance KW - Electromyography KW - Female KW - Humans KW - *Laryngeal Mucosa: physiology KW - *Laryngeal Muscles: physiology KW - Male KW - Middle Aged KW - Physical Stimulation KW - Pressure KW - *Sensory Thresholds: physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85383300?accountid=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=Suppression+of+thyroarytenoid+muscle+responses+during+repeated+air+pressure+stimulation+of+the+laryngeal+mucosa+in+awake+humans.&rft.au=Kearney%2C+Pamela+Reed%3BPoletto%2C+Christopher+J%3BMann%2C+Eric+A%3BLudlow%2C+Christy+L&rft.aulast=Kearney&rft.aufirst=Pamela&rft.date=2005-04-01&rft.volume=114&rft.issue=4&rft.spage=264&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 - SuppNotes - Cites: J Physiol. 1987 Jul;388:467-85[3656197]; Cites: Respir Physiol. 1986 Apr;64(1):45-56[3704380]; Cites: J Physiol. 1974 Jul;240(1):153-75[4855058]; Cites: Ann Otol Rhinol Laryngol. 1992 Feb;101(2 Pt 1):127-34[1739256]; Cites: J Speech Hear Res. 1971 Sep;14(3):535-43[5163887]; Cites: J Speech Hear Res. 1969 Jun;12(2):362-73[5808863]; Cites: Behav Neurosci. 1983 Oct;97(5):833-6[6639751]; Cites: Ann Otol Rhinol Laryngol. 1995 Dec;104(12):928-35[7492063]; Cites: Ann Otol Rhinol Laryngol. 1993 Oct;102(10):777-80[8215097]; Cites: Otolaryngol Head Neck Surg. 1996 Jun;114(6):761-7[8643300]; Cites: Arch Otolaryngol Head Neck Surg. 1998 Aug;124(8):897-902[9708716]; Cites: Laryngoscope. 2000 Dec;110(12):2117-22[11129033]; Cites: Ann Otol Rhinol Laryngol. 1999 Aug;108(8):725-30[10453777]; Cites: Ann Otol Rhinol Laryngol. 1999 Jun;108(6):612-9[10378532]; Cites: Neurophysiol Clin. 1999 Feb;29(1):7-38[10093816]; Cites: Laryngoscope. 1992 Feb;102(2):163-7[1738288]; Cites: Logoped Phoniatr Vocol. 2003;28(3):133-9[14596332]; Cites: Ann Otol Rhinol Laryngol. 2003 Oct;112(10):834-40[14587972]; Cites: J Appl Physiol. 2002 Nov;93(5):1622-9[12381746]; Cites: Ann Otol Rhinol Laryngol. 1972 Feb;81(1):59-71[5009816] N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Anterior vocal commissure invasion in laryngeal carcinoma diagnosis. AN - 85378930; pmid-15805888 AB - Laryngeal carcinoma involving anterior vocal commissure (AVC) represents a great challenge for staging and treatment.To compare laryngoscopy and computed tomography (CT) scan efficiency in staging tumors extending to the AVC. We also analyzed the helicoidal axial CT scan accuracy in recognizing this larynx subregion invasion.Fifty-two glottic and supraglottic laryngeal squamous cell carcinoma patients with tumoral extension to the AVC were prospectively studied from August 2001 to August 2003 at the National Cancer Institute (Rio de Janeiro, Brazil). All patients underwent videolaryngoscopic examination and direct laryngoscopy for lesion extension analysis and biopsy. After AVC helicoidal axial CT scan with sagittal and coronal 1.0 mm thick reconstruction, patients were submitted to surgical treatment. The same pathologist analyzed all surgical specimens.When compared with pathologic stage, clinical endoscopic classification was correct in 40.38% of cases (40% for T1, 29.41% for T2, 46.43% for T3, and 50% in T4). Helicoidal axial CT scan accuracy for AVC tumors was 75% (P = .0001), being more important for T2 (62.50%), T3 (73.91%), and T4 (88.24%) lesions. Identification of radiologic signs described as gross radiologic anterior commissure involvement (GRACI) increased radiologic image staging accuracy to over 96%.Endoscopic evaluation understaged tumors in all clinical stages but really T1. Helicoidal axial CT scan reformatted to 1.0 mm thick played an important role in correctly staging more advanced AVC laryngeal tumors. Radiologic signs, here identified as GRACI, may be very helpful for tomographic staging and patient treatment. JF - The Laryngoscope AU - Barbosa, M M AU - Araújo, V J F AU - Boasquevisque, E AU - Carvalho, R AU - Romano, S AU - Lima, R A AU - Dias, F L AU - Salviano, S K AD - Head and Neck Department, National Cancer Institute, Rio de Janeiro, Brazil. maurom.barbosa@globo.com Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 724 EP - 730 VL - 115 IS - 4 SN - 0023-852X, 0023-852X KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Aged KW - Aged, 80 and over KW - Biopsy KW - *Carcinoma, Squamous Cell: diagnosis KW - Carcinoma, Squamous Cell: pathology KW - Female KW - Glottis: pathology KW - Humans KW - Image Processing, Computer-Assisted: methods KW - *Laryngeal Neoplasms: diagnosis KW - Laryngeal Neoplasms: pathology KW - Laryngoscopy: statistics & numerical data KW - Male KW - Middle Aged KW - Neoplasm Invasiveness KW - Neoplasm Staging KW - Prospective Studies KW - Thyroid Cartilage: pathology KW - Tomography, Spiral Computed: statistics & numerical data KW - Tomography, X-Ray Computed: statistics & numerical data KW - Video Recording KW - *Vocal Cords: pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85378930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Laryngoscope&rft.atitle=Anterior+vocal+commissure+invasion+in+laryngeal+carcinoma+diagnosis.&rft.au=Barbosa%2C+M+M%3BAra%C3%BAjo%2C+V+J+F%3BBoasquevisque%2C+E%3BCarvalho%2C+R%3BRomano%2C+S%3BLima%2C+R+A%3BDias%2C+F+L%3BSalviano%2C+S+K&rft.aulast=Barbosa&rft.aufirst=M&rft.date=2005-04-01&rft.volume=115&rft.issue=4&rft.spage=724&rft.isbn=&rft.btitle=&rft.title=The+Laryngoscope&rft.issn=0023852X&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage mouse skin carcinogenesis. AN - 68485421; 16101330 AB - Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (p<0.01) reduction of the incidence and number of skin papillomas, precancerous skin lesions, along with significant (p<0.01) elevation of phase II detoxifying enzymes (GST, Catalase and SOD) and inhibition of lipid peroxidation in liver and skin. Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy. JF - Asian Pacific journal of cancer prevention : APJCP AU - Das, Rajat Kumar AU - Bhattacharya, Sudin AD - Department of Cancer Chemoprevention, Chittaranajan National Cancer Institute, Kolkata 700026, West Bengal, India. PY - 2005 SP - 181 EP - 188 VL - 6 IS - 2 SN - 1513-7368, 1513-7368 KW - Anticarcinogenic Agents KW - 0 KW - Cyanates KW - Selenium Compounds KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - selenocyanic acid KW - 5749-48-4 KW - Croton Oil KW - 8001-28-3 KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Mice KW - Lipid Peroxidation KW - Female KW - Cyanates -- pharmacology KW - Skin Neoplasms -- enzymology KW - Papilloma -- prevention & control KW - Skin Neoplasms -- chemically induced KW - Selenium Compounds -- pharmacology KW - Anticarcinogenic Agents -- pharmacology KW - Skin Neoplasms -- prevention & control KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68485421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Anti-tumour+promoting+activity+of+diphenylmethyl+selenocyanate+against+two-stage+mouse+skin+carcinogenesis.&rft.au=Das%2C+Rajat+Kumar%3BBhattacharya%2C+Sudin&rft.aulast=Das&rft.aufirst=Rajat&rft.date=2005-04-01&rft.volume=6&rft.issue=2&rft.spage=181&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 - 2005-09-20 N1 - Date created - 2005-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary cardamom inhibits the formation of azoxymethane-induced aberrant crypt foci in mice and reduces COX-2 and iNOS expression in the colon. AN - 68485395; 16101317 AB - Recently, considerable attention has been focused on identifying naturally occurring chemopreventive compounds capable of inhibiting, retarding, or reversing the multi-step carcinogenesis. The primary aim of the present study was to identify the effects of a commonly consumed spice, viz., cardamom against azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) in Swiss Albino mice. The secondary aim, was to explore the ability of cardamom to modulate the status of proliferation and apoptosis, and to understand its role in altering cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Male Swiss albino mice were injected with AOM (dose: 5mg/Kg body weight) or saline (Group 1) weekly once for two weeks. The AOM-injected mice were randomly assigned to two groups (Groups 2 and 3). While all the groups were on standard lab chow, Group 3 received oral doses of 0.5% cardamom, in aqueous suspension, daily for 8 weeks. Following treatment, significant reduction in the incidences of aberrant crypt foci (p<0.05) was observed. This reduction in ACF was accompanied by suppression of cell proliferation (mean Brdu LI in carcinogen control =13.91+/-3.31, and 0.5% cardamom =2.723+/-0.830) and induction of apoptosis (mean AI in carcinogen control=1.547+/-0.42 and 0.5% cardamom = 6.61+/-0.55). Moreover, reduction of both COX-2 and iNOS expression was also observed. These results suggest that aqueous suspensions of cardamom have protective effects on experimentally induced colon carcinogenesis. Cardamom as a whole and its active components require further attention if the use of this spice is to be recommended for cancer prevention. JF - Asian Pacific journal of cancer prevention : APJCP AU - Sengupta, Archana AU - Ghosh, Samit AU - Bhattacharjee, Shamee AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Kolkata 700026, India. archana_sen@yahoo.com PY - 2005 SP - 118 EP - 122 VL - 6 IS - 2 SN - 1513-7368, 1513-7368 KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens 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 - Azoxymethane KW - MO0N1J0SEN KW - Index Medicus KW - Animals KW - Blotting, Western KW - Azoxymethane -- toxicity KW - Random Allocation KW - Apoptosis -- drug effects KW - Carcinogens -- toxicity KW - Mice KW - Colonic Diseases -- chemically induced KW - Elettaria KW - Colonic Neoplasms -- chemically induced KW - Precancerous Conditions -- enzymology KW - Colonic Neoplasms -- enzymology KW - Colonic Diseases -- prevention & control KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Precancerous Conditions -- chemically induced KW - Anticarcinogenic Agents -- pharmacology KW - Precancerous Conditions -- prevention & control KW - Colonic Diseases -- enzymology KW - Colonic Neoplasms -- prevention & control KW - Nitric Oxide Synthase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68485395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dietary+cardamom+inhibits+the+formation+of+azoxymethane-induced+aberrant+crypt+foci+in+mice+and+reduces+COX-2+and+iNOS+expression+in+the+colon.&rft.au=Sengupta%2C+Archana%3BGhosh%2C+Samit%3BBhattacharjee%2C+Shamee&rft.aulast=Sengupta&rft.aufirst=Archana&rft.date=2005-04-01&rft.volume=45&rft.issue=4&rft.spage=388&rft.isbn=&rft.btitle=&rft.title=Annals+of+Emergency+Medicine&rft.issn=01960644&rft_id=info:doi/10.1016%2Fj.annemergmed.2004.08.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-20 N1 - Date created - 2005-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis. AN - 68432168; 16054980 AB - Alcoholic beverage consumption is classified as a known human carcinogen, causally related to an increased risk of cancer of the upper gastrointestinal tract. The formation of acetaldehyde from ethanol metabolism seems to be the major mechanism underlying this effect. Acetaldehyde is carcinogenic in rodents and causes sister chromatid exchanges and chromosomal aberrations in human cells. The best-studied DNA adduct from acetaldehyde is N(2)-ethyl-2'-deoxyguanosine, which is increased in liver DNA obtained from ethanol-treated rodents and in white blood cells obtained from human alcohol abusers. However, the carcinogenic relevance of this adduct is unclear in view of the lack of evidence that it is mutagenic in mammalian cells. A different DNA adduct, 1,N(2)-propano-2'-deoxyguanosine (PdG), can also be formed from acetaldehyde in the presence of histones and other basic molecules. PdG has been shown to be responsible for the genotoxic and mutagenic effects of crotonaldehyde. The PdG adduct can exist in either of two forms: a ring-closed form or a ring-opened aldehyde form. Whereas the ring-closed form is mutagenic, the aldehyde form can participate in the formation of secondary lesions, including DNA-protein cross-links and DNA interstrand cross-links. The formation of these types of complex secondary DNA lesions resulting from PdG may explain many of the observed genotoxic effects of acetaldehyde described above. Repair of PdG and its associated adducts is complex, involving multiple pathways. Inherited variation in the genes encoding the proteins involved in the repair of PdG and its secondary adducts may contribute to susceptibility to alcoholic beverage-related carcinogenesis. JF - Alcohol (Fayetteville, N.Y.) AU - Brooks, Philip J AU - Theruvathu, Jacob A AD - Section on Molecular Neurobiology, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 3S32, MSC 9412, Bethesda, MD 20892-9412, USA. pjbrooks@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 187 EP - 193 VL - 35 IS - 3 SN - 0741-8329, 0741-8329 KW - DNA Adducts KW - 0 KW - Mutagens KW - Acetaldehyde KW - GO1N1ZPR3B KW - Index Medicus KW - DNA Repair -- genetics KW - Animals KW - Risk Factors KW - Polymorphism, Genetic -- genetics KW - Humans KW - Mutagens -- toxicity KW - Alcohol Drinking -- adverse effects KW - Acetaldehyde -- toxicity KW - Acetaldehyde -- metabolism KW - Alcohol Drinking -- genetics KW - Neoplasms -- genetics KW - Neoplasms -- etiology KW - DNA Adducts -- metabolism KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68432168?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=DNA+adducts+from+acetaldehyde%3A+implications+for+alcohol-related+carcinogenesis.&rft.au=Brooks%2C+Philip+J%3BTheruvathu%2C+Jacob+A&rft.aulast=Brooks&rft.aufirst=Philip&rft.date=2005-04-01&rft.volume=35&rft.issue=3&rft.spage=187&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 - 2005-11-30 N1 - Date created - 2005-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemiology of alcohol-associated cancers. AN - 68432140; 16054977 AB - Alcohol, especially in combination with smoking, is a well-established risk factor for cancers of the oral cavity and pharynx, esophagus, and larynx, with 25% to 80% of these cancers being attributable to alcohol. Rates of these cancers in the United States have been decreasing in recent years, possibly because of reductions in cigarette smoking and alcohol use. Chronic alcohol consumption has been linked with increased risk of liver cancer in epidemiologic studies. However, the rising rates of this cancer in the United States are most likely due to the increasing prevalence of chronic hepatitis B and C infections. Epidemiologic evidence has linked light to moderate intake of alcohol to cancers of the colorectum and female breast. These cancers are common in developed countries, so even small increases in risk can have important public health implications. Although results of most epidemiologic studies have provided little or no support for a causal relation between light and moderate alcohol use and risk of pancreatic cancer, a possible role of heavy alcohol consumption cannot be ruled out. Further studies of these cancers are needed to clarify the role of type of alcoholic beverage, the role of alcohol concentration, and the dose-response curve at low concentrations of alcohol. Future research also should be designed to promote the use of uniform ways to report alcohol intake and uniform measures for analysis, to include the investigation of alcohol-associated cancer risks in U.S. minority populations, to enhance experimental work to better understand the underlying mechanisms through which alcohol promotes carcinogenesis, and to develop preventive strategies. JF - Alcohol (Fayetteville, N.Y.) AU - Brown, Linda Morris AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 6120 Executive Boulevard, Room 8026, MSC 7244, Bethesda, MD 20892-7244, USA. brownl@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 161 EP - 168 VL - 35 IS - 3 SN - 0741-8329, 0741-8329 KW - Index Medicus KW - Age Factors KW - Humans KW - Digestive System Neoplasms -- epidemiology KW - Aging KW - Adult KW - Aged KW - Middle Aged KW - Respiratory Tract Neoplasms -- epidemiology KW - United States -- epidemiology KW - Male KW - Female KW - Ethnic Groups -- statistics & numerical data KW - Neoplasms -- epidemiology KW - Alcohol Drinking -- adverse effects KW - Alcohol Drinking -- epidemiology KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68432140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Epidemiology+of+alcohol-associated+cancers.&rft.au=Brown%2C+Linda+Morris&rft.aulast=Brown&rft.aufirst=Linda&rft.date=2005-04-01&rft.volume=35&rft.issue=3&rft.spage=161&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 - 2005-11-30 N1 - Date created - 2005-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanisms of alcohol-associated cancers: introduction and summary of the symposium. AN - 68429688; 16054976 AB - Chronic alcohol consumption is associated with an increased risk for cancers of many organs, such as oral cavity, pharynx, larynx, and esophagus; breast; liver; ovary; colon; rectum; stomach; and pancreas. An understanding of the underlying mechanisms by which chronic alcohol consumption promotes carcinogenesis is important for development of appropriate strategies for prevention and treatment of alcohol-associated cancers. The National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, Office of Rare Diseases, National Cancer Institute, National Institute on Drug Abuse, and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, sponsored an international symposium on Mechanisms of Alcohol-Associated Cancers in Bethesda, Maryland, USA, October 2004. The following is a summary of the symposium. Chronic ethanol consumption may promote carcinogenesis by (1) production of acetaldehyde, which is a weak mutagen and carcinogen; (2) induction of cytochrome P450 2E1 and associated oxidative stress and conversion of procarcinogens to carcinogens; (3) depletion of S-adenosylmethionine and, consequently, induction of global DNA hypomethylation; (4) induction of increased production of inhibitory guanine nucleotide regulatory proteins and components of extracellular signal-regulated kinase-mitogen-activated protein kinase signaling; (5) accumulation of iron and associated oxidative stress; (6) inactivation of the tumor suppressor gene BRCA1 and increased estrogen responsiveness (primarily in breast); and (7) impairment of retinoic acid metabolism. Nicotine may promote carcinogenesis through activation of extracellular signal-regulated kinase/cyclooxygenase-2/vascular endothelial growth factor signaling pathway. JF - Alcohol (Fayetteville, N.Y.) AU - Purohit, Vishnudutt AU - Khalsa, Jag AU - Serrano, Jose AD - Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers Lane, Room 2035, Bethesda, MD 20892-9304, USA. vpurohit@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 155 EP - 160 VL - 35 IS - 3 SN - 0741-8329, 0741-8329 KW - Carcinogens KW - 0 KW - Ethanol KW - 3K9958V90M KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Acetaldehyde KW - GO1N1ZPR3B KW - Index Medicus KW - Oxidative Stress -- physiology KW - Alcoholism -- etiology KW - Carcinogens -- metabolism KW - Humans KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Acetaldehyde -- metabolism KW - Alcoholism -- genetics KW - Alcoholism -- complications KW - Neoplasms -- epidemiology KW - Alcohol Drinking -- adverse effects KW - Ethanol -- toxicity KW - Ethanol -- metabolism KW - Alcohol Drinking -- epidemiology KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68429688?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Initial+Ocular+Following+in+Humans+Depends+Critically+on+the+Fourier+Components+of+the+Motion+Stimulus&rft.au=Chen%2C+K+J%3BSheliga%2C+B+M%3BFitzgibbon%2C+E+J%3BMiles%2C+F+A&rft.aulast=Chen&rft.aufirst=K&rft.date=2005-04-01&rft.volume=1039&rft.issue=1&rft.spage=260&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1196%2Fannals.1325.025 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-11-30 N1 - Date created - 2005-08-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactive oxygen species as mediators of cellular senescence. AN - 68066668; 16036611 AB - Aging has often been viewed as a random process arising from the accumulation of both genetic and epigenetic changes. Increasingly, the notion that aging is a stochastic process is being supplanted by the concept that maximum lifespan of an organism is tightly regulated. This knowledge has led to a growing overlap between classical signal transduction paradigms and the biology of aging. We review certain specific examples where these seemingly disparate disciplines intersect. In particular, we review the concept that intracellular reactive oxygen species function as signalling molecules and that oxidants play a central role as mediators of cellular senescence. JF - IUBMB life AU - Colavitti, Renata AU - Finkel, Toren AD - Cardiovascular Branch, NHLBI, NIH, Bethesda, Maryland 20892-1454, USA. PY - 2005 SP - 277 EP - 281 VL - 57 IS - 4-5 SN - 1521-6543, 1521-6543 KW - Free Radicals KW - 0 KW - Oxidants KW - Reactive Oxygen Species KW - Telomerase KW - EC 2.7.7.49 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - MAP Kinase Signaling System KW - Oxidants -- pharmacology KW - Cell Aging KW - Oxygen -- metabolism KW - Humans KW - Oxidative Stress KW - Transcription, Genetic KW - Telomerase -- metabolism KW - Models, Biological KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68066668?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IUBMB+life&rft.atitle=Reactive+oxygen+species+as+mediators+of+cellular+senescence.&rft.au=Colavitti%2C+Renata%3BFinkel%2C+Toren&rft.aulast=Colavitti&rft.aufirst=Renata&rft.date=2005-04-01&rft.volume=57&rft.issue=4-5&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=IUBMB+life&rft.issn=15216543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-16 N1 - Date created - 2005-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adjunctive strategies in the treatment of refractory bipolar depression: clinician options in the absence of a systematic database. AN - 67898536; 15934880 AB - Multiple approaches to enhancing antidepressant treatment response in bipolar depression are available and should, in many instances, be explored despite a lack of definitive controlled trial literature supporting their efficacy. Given that the morbidity of depression is three times greater than mania in bipolar illness, a range of treatment approaches to this phase of illness should be pursued. This paper highlights the preliminary evidence of efficacy versus side effects, tolerability, and safety in order to suggest an overall provisional utility grade for each well-studied to highly-experimental option. Given the general paucity of evidence to support efficacy or to sequence different approaches for augmenting treatment of bipolar depression, it is critical that patient and physician adopt a systematic and, preferably, daily rating approach to the assessment of benefit for a given patient of each strategy contemplated. The goal is to achieve and maintain remission of depressive symptoms and associated comorbidities, which is often not accomplished using primary mood stabilizer treatments alone, or in combination; thus, an active clinical approach to augmentation strategies is indicated even when the literature provides only highly preliminary guidance. JF - Expert opinion on pharmacotherapy AU - Post, Robert M AD - Biological Psychiatry Branch, National Institutes of Health, National Institute of Mental Health, Department of Health and Human Services, 10 Center Drive MSC 1272, Bldg. 10, Room 3S239, Bethesda, MD 20892-1272, USA. Robert.Post@nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 531 EP - 546 VL - 6 IS - 4 KW - Antidepressive Agents KW - 0 KW - Index Medicus KW - Dizziness -- chemically induced KW - Weight Gain -- drug effects KW - Humans KW - Databases, Factual -- statistics & numerical data KW - Bipolar Disorder -- drug therapy KW - Bipolar Disorder -- psychology KW - Antidepressive Agents -- therapeutic use KW - Physician's Role KW - Antidepressive Agents -- adverse effects KW - Databases, Factual -- classification KW - Antidepressive Agents -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67898536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Adjunctive+strategies+in+the+treatment+of+refractory+bipolar+depression%3A+clinician+options+in+the+absence+of+a+systematic+database.&rft.au=Post%2C+Robert+M&rft.aulast=Post&rft.aufirst=Robert&rft.date=2005-04-01&rft.volume=6&rft.issue=4&rft.spage=531&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+pharmacotherapy&rft.issn=1744-7666&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-04-14 N1 - Date created - 2005-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [A validation of the applicability of the Severity of Dependence Scale (SDS) in a nationwide mental hospital survey on substance-related psychiatric disorders]. AN - 67862015; 15912744 AB - We studied the applicability of the Severity of Dependence Scale (SDS) in a nationwide mental hospital survey on substance-related psychiatric disorders in 2002. The SDS is an easily administered five-item scale used to assess psychological dependence, especially the compulsive use of a wide range of substances. The SDS was translated into Japanese (SDS-J) and administered as a part of a questionnaire to 114 patients with substance-dependence syndrome in the survey. The SDS-J had a good internal consistency as demonstrated by the high Cronbach's alpha (0.76). Principal component analyses (PCA) with varimax rotation on the five items revealed a single-factor solution that accounted for 50.8% of the variance. Pearson's correlation coefficient between each item and total score ranged from 0.68 to 0.76, all of which were significant (p<.01). The total score of the SDS-J and the total number of items and psychological dependence-related items in the diagnostic guideline of dependence syndrome of the ICD-10 had rather low Pearson's correlation coefficients (0.17 and 0.23), but those correlations were significant (p < .05 and p < .01). The PCA for the patients with methamphetamine dependence also revealed a single-factor solution that accounted for 55.0% of the total variance. The results indicate that the SDS-J has satisfactory internal and structural reliability and external criteria validity. It also suggests that the SDS-J might be useful for assessing dependence syndrome in clinical settings in Japan, where those substances having properties of causing particularly severe psychological dependence, such as methamphetamine and solvents, are the most common substances of abuse. JF - Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence AU - Ozaki, Shigeru AU - Wada, Kiyoshi AD - Department of Drug Dependence Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 126 EP - 136 VL - 40 IS - 2 SN - 1341-8963, 1341-8963 KW - Methamphetamine KW - 44RAL3456C KW - Index Medicus KW - Humans KW - Adult KW - Data Collection KW - Male KW - Japan KW - Female KW - Severity of Illness Index KW - Psychoses, Substance-Induced -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67862015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.atitle=%5BA+validation+of+the+applicability+of+the+Severity+of+Dependence+Scale+%28SDS%29+in+a+nationwide+mental+hospital+survey+on+substance-related+psychiatric+disorders%5D.&rft.au=Ozaki%2C+Shigeru%3BWada%2C+Kiyoshi&rft.aulast=Ozaki&rft.aufirst=Shigeru&rft.date=2005-04-01&rft.volume=40&rft.issue=2&rft.spage=126&rft.isbn=&rft.btitle=&rft.title=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.issn=13418963&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-28 N1 - Date created - 2005-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Micafungin: pharmacology, experimental therapeutics and clinical applications. AN - 67814501; 15882123 AB - Invasive fungal infections are important causes of morbidity and mortality in hospitalised patients. Current therapy with amphotericin B and antifungal triazoles has overlapping targets and is limited by toxicity and resistance. Echinocandins are a new class of antifungal drugs, which inhibit the synthesis of 1,3-beta-D-glucan. This homopolysaccharide is an important component of the cell wall of many pathogenic fungi, providing osmotic stability and functioning in cell growth and cell division. Micafungin, which is a member of the echinocandin class, exhibits in vitro fungicidal or fungistatic activity against a variety of fungal pathogens which include Candida and Aspergillus species but not Cryptococcus, Fusarium or Zygomycetes. Micafungin demonstrates linear pharmacokinetics, which are not altered by drugs metabolised through the P450 enzyme system. The preclinical and clinical data strongly support the development of micafungin for treatment of proven or suspected mucosal and invasive Candida infections in immunocompetent and immunocompromised patients. This paper reviews the preclinical and clinical pharmacology of micafungin and its potential role for treatment of fungal invasive infections in patients. JF - Expert opinion on investigational drugs AU - Groll, Andreas H AU - Stergiopoulou, Theodouli AU - Roilides, Emmanuel AU - Walsh, Thomas J AD - Pediatric Oncology Branch, National Cancer Institute, Building 10, Room 1-3888, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 489 EP - 509 VL - 14 IS - 4 KW - Antifungal Agents KW - 0 KW - Echinocandins KW - Lipopeptides KW - Lipoproteins KW - Peptides, Cyclic KW - micafungin KW - R10H71BSWG KW - Index Medicus KW - Animals KW - Randomized Controlled Trials as Topic KW - Humans KW - Aspergillosis -- drug therapy KW - Disease Models, Animal KW - Aspergillus -- drug effects KW - Candidiasis -- drug therapy KW - Candida -- drug effects KW - Candida -- growth & development KW - Microbial Sensitivity Tests KW - Aspergillus -- growth & development KW - Lipoproteins -- pharmacology KW - Peptides, Cyclic -- therapeutic use KW - Antifungal Agents -- pharmacology KW - Lipoproteins -- therapeutic use KW - Mycoses -- drug therapy KW - Peptides, Cyclic -- pharmacology KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67814501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Micafungin%3A+pharmacology%2C+experimental+therapeutics+and+clinical+applications.&rft.au=Groll%2C+Andreas+H%3BStergiopoulou%2C+Theodouli%3BRoilides%2C+Emmanuel%3BWalsh%2C+Thomas+J&rft.aulast=Groll&rft.aufirst=Andreas&rft.date=2005-04-01&rft.volume=14&rft.issue=4&rft.spage=489&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+investigational+drugs&rft.issn=1744-7658&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-11-14 N1 - Date created - 2005-05-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clodronate in the prevention and treatment of skeletal metastasis. AN - 67803869; 15877520 AB - Many solid tumors, including breast and prostate cancer, metastasize to bone, thereby putting patients at high risk for developing skeletal complications including pathologic fracture, spinal cord compression and debilitating bone pain. Patients often live for many years after developing bone metastasis, a fact that highlights the importance of therapies to reduce morbidity from skeletal complications. Bisphosphonates, including clodronate, have been shown to be useful in reducing skeletal complications in patients with cancer. This review will highlight the role of clodronate for skeletal metastasis. JF - Expert review of anticancer therapy AU - Gulley, James AU - Dahut, William L AD - National Cancer Institute, Laboratory of Tumor Immunology and Biology, Center for Cancer Research, 10 Center Drive, 8B07 MSC 1750, Bethesda, MD 20892, USA. gulleyj@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 221 EP - 230 VL - 5 IS - 2 KW - Bone Density Conservation Agents KW - 0 KW - Clodronic Acid KW - 0813BZ6866 KW - Index Medicus KW - Prostatic Neoplasms -- pathology KW - Breast Neoplasms -- pathology KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Clinical Trials as Topic KW - Morbidity KW - Male KW - Female KW - Clodronic Acid -- pharmacology KW - Bone Neoplasms -- prevention & control KW - Bone Density Conservation Agents -- therapeutic use KW - Bone Density Conservation Agents -- pharmacology KW - Clodronic Acid -- therapeutic use KW - Clodronic Acid -- administration & dosage KW - Bone Density Conservation Agents -- pharmacokinetics KW - Clodronic Acid -- pharmacokinetics KW - Clodronic Acid -- adverse effects KW - Bone Neoplasms -- secondary KW - Bone Density Conservation Agents -- administration & dosage KW - Bone Density Conservation Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67803869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+review+of+anticancer+therapy&rft.atitle=Clodronate+in+the+prevention+and+treatment+of+skeletal+metastasis.&rft.au=Gulley%2C+James%3BDahut%2C+William+L&rft.aulast=Gulley&rft.aufirst=James&rft.date=2005-04-01&rft.volume=5&rft.issue=2&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Expert+review+of+anticancer+therapy&rft.issn=1744-8328&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-02-07 N1 - Date created - 2005-05-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Rad1-Rad10 complex promotes the production of gross chromosomal rearrangements from spontaneous DNA damage in Saccharomyces cerevisiae. AN - 67801761; 15687264 AB - Gross chromosomal rearrangements (GCRs) have been observed in many cancers. Previously, we have demonstrated many mechanisms for suppression of GCR formation in yeast. However, pathways that promote the formation of GCRs are not as well understood. Here, we present evidence that the Rad1-Rad10 endonuclease, which plays an important role in nucleotide excision and recombination repairs, has a novel role to produce GCRs. A mutation of either the RAD1 or the RAD10 gene reduced GCR rates in many GCR mutator strains. The inactivation of Rad1 or Rad10 in GCR mutator strains also slightly enhanced methyl methanesulfonate sensitivity. Although the GCRs induced by treatment with DNA-damaging agents were not reduced by rad1 or rad10 mutations, the translocation- and deletion-type GCRs created by a single double-strand break are mostly replaced by de novo telomere-addition-type GCR. Results presented here suggest that Rad1-Rad10 functions at different stages of GCR formation and that there is an alternative pathway for the GCR formation that is independent of Rad1-Rad10. JF - Genetics AU - Hwang, Ji-Young AU - Smith, Stephanie AU - Myung, Kyungjae AD - Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 1927 EP - 1937 VL - 169 IS - 4 SN - 0016-6731, 0016-6731 KW - DNA, Single-Stranded KW - 0 KW - DNA-Binding Proteins KW - Mutagens KW - Saccharomyces cerevisiae Proteins KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Endonucleases KW - EC 3.1.- KW - RAD1 protein, S cerevisiae KW - RAD10 protein, S cerevisiae KW - EC 3.1.30.1 KW - Single-Strand Specific DNA and RNA Endonucleases KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Genotype KW - Plasmids -- metabolism KW - DNA, Single-Stranded -- genetics KW - Genetic Techniques KW - DNA Damage KW - Models, Genetic KW - Crosses, Genetic KW - Mutagens -- pharmacology KW - Mutation KW - Methyl Methanesulfonate -- pharmacology KW - Gene Deletion KW - Saccharomyces cerevisiae -- genetics KW - Endonucleases -- metabolism KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Saccharomyces cerevisiae -- physiology KW - Recombination, Genetic KW - Chromosomes -- ultrastructure KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67801761?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=The+Rad1-Rad10+complex+promotes+the+production+of+gross+chromosomal+rearrangements+from+spontaneous+DNA+damage+in+Saccharomyces+cerevisiae.&rft.au=Hwang%2C+Ji-Young%3BSmith%2C+Stephanie%3BMyung%2C+Kyungjae&rft.aulast=Hwang&rft.aufirst=Ji-Young&rft.date=2005-04-01&rft.volume=169&rft.issue=4&rft.spage=1927&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-25 N1 - Date created - 2005-05-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell. 2003 Dec;12(6):1489-98 [14690602] Eukaryot Cell. 2004 Dec;3(6):1557-66 [15590829] Mol Cell Biol. 2004 Jul;24(13):5776-87 [15199134] Mutat Res. 2001 Aug 9;486(3):167-84 [11459630] Cell. 2001 Nov 16;107(4):537-48 [11719193] Nat Rev Cancer. 2001 Oct;1(1):22-33 [11900249] Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4500-7 [11917116] Mol Cell. 2002 May;9(5):1067-78 [12049742] Science. 2002 Jul 26;297(5581):552-7 [12142524] Genes Dev. 2002 Oct 15;16(20):2639-49 [12381663] Mol Cell. 2002 Sep;10(3):441-2 [12408814] Trends Cell Biol. 2002 Nov;12(11):509-16 [12446112] Microbiol Mol Biol Rev. 2002 Dec;66(4):630-70, table of contents [12456786] DNA Repair (Amst). 2003 Mar 1;2(3):243-58 [12547388] Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):776-81 [12552134] Trends Genet. 2003 May;19(5):253-6 [12711216] Mutat Res. 2000 Jun 30;451(1-2):13-24 [10915862] Mutat Res. 2000 Jun 30;451(1-2):187-96 [10915872] Science. 2000 Aug 4;289(5480):771-4 [10926538] Nat Genet. 2001 Jan;27(1):113-6 [11138010] Cancer Res. 2001 Feb 1;61(3):1214-9 [11221853] Nat Genet. 2001 Mar;27(3):247-54 [11242102] Cell. 2001 Feb 9;104(3):397-408 [11239397] Nature. 2001 Jun 28;411(6841):1073-6 [11429610] Cell Mol Life Sci. 2001 May;58(5-6):665-72 [11437228] Mol Cell. 2003 May;11(5):1379-87 [12769860] Proc Natl Acad Sci U S A. 2003 May 27;100(11):6640-5 [12750463] Genes Dev. 2003 Jul 15;17(14):1741-54 [12865298] EMBO J. 2003 Aug 15;22(16):4304-13 [12912927] Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9906-11 [12909721] Curr Biol. 2003 Sep 16;13(18):1583-95 [13678589] Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11529-34 [12972632] Mol Cell. 2003 Sep;12(3):761-74 [14527420] Mol Cell Biol. 2003 Dec;23(23):8820-8 [14612421] Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9039-44 [15184655] Genes Dev. 2004 Sep 15;18(18):2283-91 [15371342] Mol Cell Biol. 1988 Sep;8(9):3619-26 [3065620] Mol Cell Biol. 1990 Jun;10(6):2485-91 [2188090] Nat Genet. 1993 Nov;5(3):217-24 [8275084] Proc Natl Acad Sci U S A. 1994 May 24;91(11):5017-21 [8197175] Mol Cell Biol. 1995 Apr;15(4):2245-51 [7891718] Cell. 1995 Mar 24;80(6):859-68 [7697716] Bioessays. 1997 Mar;19(3):233-40 [9080773] Mol Cell Biol. 1997 May;17(5):2764-73 [9111347] Curr Biol. 1997 Jun 1;7(6):427-39 [9197240] Annu Rev Biochem. 1997;66:61-92 [9242902] Cell. 1998 Nov 25;95(5):583-6 [9845359] Nature. 1998 Dec 17;396(6712):643-9 [9872311] Curr Opin Genet Dev. 1999 Feb;9(1):89-96 [10072354] Nat Genet. 1999 Sep;23(1):81-5 [10471504] Prog Nucleic Acid Res Mol Biol. 1999;63:189-221 [10506832] Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15980-5 [15514023] Nat Genet. 2004 Jun;36(6):612-7 [15133512] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hormones and endometrial cancer--new data from the Million Women Study. AN - 67792036; 15866289 JF - Lancet (London, England) AU - Brinton, Louise A AU - Lacey, James V AU - Trimble, Edward L AD - National Cancer Institute, Bethesda, MD 20892, USA. brinton@nih.gov PY - 2005 SP - 1517 EP - 1518 VL - 365 IS - 9470 KW - Estrogens, Conjugated (USP) KW - 0 KW - Norpregnenes KW - tibolone KW - FF9X0205V2 KW - Abridged Index Medicus KW - Index Medicus KW - Risk KW - Estrogens, Conjugated (USP) -- administration & dosage KW - Risk Factors KW - Humans KW - Middle Aged KW - Female KW - Estrogens, Conjugated (USP) -- adverse effects KW - Norpregnenes -- adverse effects KW - Endometrial Neoplasms -- chemically induced KW - Estrogen Replacement Therapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67792036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Hormones+and+endometrial+cancer--new+data+from+the+Million+Women+Study.&rft.au=Brinton%2C+Louise+A%3BLacey%2C+James+V%3BTrimble%2C+Edward+L&rft.aulast=Brinton&rft.aufirst=Louise&rft.date=2005-04-01&rft.volume=365&rft.issue=9470&rft.spage=1517&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=1474-547X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-24 N1 - Date created - 2005-05-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Lancet. 2005 Apr 30-May 6;365(9470):1543-51 [15866308] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of psychotherapy attendance on buprenorphine treatment outcome. AN - 67787651; 15857725 AB - We evaluated the influence of psychotherapy attendance on treatment outcome in 90 dually (cocaine and heroin) dependent outpatients who completed 70 days of a controlled clinical trial of sublingual buprenorphine (16 mg, 8 mg, or 2 mg daily, or 16 mg every other day) plus weekly individual standardized interpersonal cognitive psychotherapy. Treatment outcome was evaluated by quantitative urine benzoylecgonine (BZE) and morphine levels (log-transformed), performed three times per week. Repeated-measures linear regression was used to assess the effects of psychotherapy attendance (percent of visits kept), medication group, and study week on urine drug metabolite levels. Mean psychotherapy attendance was 71% of scheduled visits. Higher psychotherapy attendance was associated with lower urine BZE levels, and this association grew more pronounced as the study progressed (p=0.04). The inverse relationship between psychotherapy attendance and urine morphine levels varied by medication group, being most pronounced for subjects receiving 16 mg every other day (p=0.02). These results suggest that psychotherapy can improve the outcome of buprenorphine maintenance treatment for patients with dual (cocaine and opioid) dependence. JF - Journal of substance abuse treatment AU - Montoya, Iván D AU - Schroeder, Jennifer R AU - Preston, Kenzie L AU - Covi, Lino AU - Umbricht, Annie AU - Contoreggi, Carlo AU - Fudala, Paul J AU - Johnson, Rolley E AU - Gorelick, David A AD - Division of Pharmacotherapies and Medical Consequences of Drug Abuse, National Institute on Drug Abuse, National Institutes of Health, Department of Health & Human Services, Rockville, MD 20892, USA. imontoya@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 247 EP - 254 VL - 28 IS - 3 SN - 0740-5472, 0740-5472 KW - Narcotic Antagonists KW - 0 KW - Buprenorphine KW - 40D3SCR4GZ KW - Index Medicus KW - Combined Modality Therapy KW - Humans KW - Adult KW - Treatment Outcome KW - Administration, Sublingual KW - Male KW - Female KW - Narcotic Antagonists -- administration & dosage KW - Buprenorphine -- therapeutic use KW - Opioid-Related Disorders -- psychology KW - Narcotic Antagonists -- therapeutic use KW - Psychotherapy KW - Patient Compliance -- psychology KW - Cocaine-Related Disorders -- psychology KW - Buprenorphine -- administration & dosage KW - Opioid-Related Disorders -- therapy KW - Cocaine-Related Disorders -- therapy KW - Opioid-Related Disorders -- urine KW - Cocaine-Related Disorders -- urine UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67787651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Influence+of+psychotherapy+attendance+on+buprenorphine+treatment+outcome.&rft.au=Montoya%2C+Iv%C3%A1n+D%3BSchroeder%2C+Jennifer+R%3BPreston%2C+Kenzie+L%3BCovi%2C+Lino%3BUmbricht%2C+Annie%3BContoreggi%2C+Carlo%3BFudala%2C+Paul+J%3BJohnson%2C+Rolley+E%3BGorelick%2C+David+A&rft.aulast=Montoya&rft.aufirst=Iv%C3%A1n&rft.date=2005-04-01&rft.volume=28&rft.issue=3&rft.spage=247&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 - 2005-10-11 N1 - Date created - 2005-04-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Exp Clin Psychopharmacol. 2000 May;8(2):176-84 [10843300] Drug Alcohol Depend. 1994 Jan;34(2):87-97 [8026305] J Consult Clin Psychol. 2001 Feb;69(1):119-24 [11302268] J Consult Clin Psychol. 2001 Oct;69(5):825-30 [11680559] Am J Drug Alcohol Abuse. 2001 Nov;27(4):617-31 [11727880] Am J Addict. 2002 Winter;11(1):24-40 [11876581] Acta Psychiatr Scand. 2002 Mar;105(3):164-72 [11939969] Arch Gen Psychiatry. 2002 Sep;59(9):817-24 [12215081] J Subst Abuse Treat. 2002 Sep;23(2):81-6 [12220605] Addict Behav. 2002 Nov-Dec;27(6):887-910 [12369474] J Subst Abuse Treat. 2002 Oct;23(3):191-7 [12392805] Arch Gen Psychiatry. 2003 Apr;60(4):402-7 [12695318] Addiction. 2003 May;98(5):665-71 [12751984] Arch Gen Psychiatry. 1999 Sep;56(9):812-20 [12884887] Arch Gen Psychiatry. 1994 Dec;51(12):989-97 [7979888] Psychopharmacology (Berl). 1994 Dec;116(4):401-6 [7701040] J Subst Abuse. 1995;7(1):9-26 [7655314] Am J Drug Alcohol Abuse. 1995 Aug;21(3):327-44 [7484983] Arch Gen Psychiatry. 1996 May;53(5):409-15 [8624184] J Consult Clin Psychol. 1996 Jun;64(3):619-22 [8698958] J Subst Abuse Treat. 1995 Nov-Dec;12(6):415-21 [8749725] Addiction. 1997 Mar;92(3):297-302 [9219391] Arch Gen Psychiatry. 1997 Aug;54(8):713-20 [9283506] J Consult Clin Psychol. 1997 Oct;65(5):803-10 [9337499] Psychother Psychosom. 1998;67(1):3-9 [9491434] J Consult Clin Psychol. 1999 Feb;67(1):13-8 [10028204] Arch Gen Psychiatry. 1999 Sep;56(9):829-35 [12884889] Br J Psychiatry. 1999 Jun;174:505-11 [10616628] Drug Alcohol Depend. 2000 Feb 1;58(1-2):205-12 [10669073] Arch Gen Psychiatry. 2000 Apr;57(4):395-404 [10768702] Bipolar Disord. 2002;4 Suppl 1:102 [12479692] Addiction. 2003 Jan;98(1):7-22 [12492751] J Addict Dis. 2003;22(1):35-55 [12661978] Psychol Addict Behav. 2003 Mar;17(1):73-82 [12665084] J Clin Psychiatry. 2003 Sep;64(9):1101-5 [14628987] J Clin Psychol. 2004 Jan;60(1):29-41 [14692007] Clin Pharmacol Ther. 2004 Jan;75(1):34-48 [14749690] Int J Addict. 1985 Jun-Jul;20(6-7):869-96 [3908340] Am J Drug Alcohol Abuse. 1985;11(3-4):171-91 [4091157] Psychopharmacol Bull. 1987;23(1):173-6 [3602315] Life Sci. 1989;44(13):887-92 [2927249] Biol Psychiatry. 1989 Oct;26(6):637-9 [2790101] JAMA. 1993 Apr 21;269(15):1953-9 [8385230] Biol Psychiatry. 1993 Jul 1-15;34(1-2):66-74 [8373940] J Clin Psychopharmacol. 1993 Aug;13(4):243-50 [8376611] Am J Psychiatry. 1993 Nov;150(11):1755 [8214197] J Addict Dis. 1993;12(3):155-70 [8251541] J Clin Psychiatry. 2000 Sep;61(9):698-705; quiz 706 [11030495] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Test-retest of self-reported exposure to artificial tanning devices, self-tanning creams, and sun sensitivity showed consistency. AN - 67780398; 15862730 AB - Exposure to ultraviolet radiation has consistently been linked to an increased risk of melanoma. Epidemiologic studies are susceptible to measurement error, which can distort the magnitude of observed effects. Although the reliability of self-report of many sun exposure factors has been previously described in several studies, self-report of use of artificial tanning devices and self-tanning creams has been less well characterized. A mailed survey was re-administered 2-4 weeks after completion of the initial survey to 76 randomly selected participants in a case-control study of melanoma. Cases and controls were individuals diagnosed in 1999 and 2000 who were ascertained from the Iowa Cancer Registry in 2002. We assessed the consistency of self-reported use of sunlamps and self-tanning creams, sun sensitivity, and history of sunburns. There was substantial reliability in reporting the use of sunlamps or self-tanning creams (cases: Kappa (kappa)=1.0 for both exposures; controls: kappa=0.71 and 0.87, respectively). kappa estimates of 0.62-0.78 were found for overall reliability of several sun sensitivity factors. Overall, the survey instrument demonstrated substantial reproducibility for factors related to the use of sunlamps or tanning beds, self-tanning creams, and sun sensitivity factors. JF - Journal of clinical epidemiology AU - Beane Freeman, Laura E AU - Dennis, Leslie K AU - Lynch, Charles F AU - Lowe, John B AU - Clarke, William R AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Occupational and Environmental Epidemiology Branch, 6120, Executive Boulevard, Suite 511, MSC 7240, Bethesda, MD 20892-7344, USA. freemala@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 430 EP - 432 VL - 58 IS - 4 SN - 0895-4356, 0895-4356 KW - Cosmetics KW - 0 KW - Index Medicus KW - Reproducibility of Results KW - Aged, 80 and over KW - Sunburn KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Beauty Culture KW - Male KW - Female KW - Cosmetics -- administration & dosage KW - Skin Neoplasms -- etiology KW - Melanoma -- etiology KW - Health Surveys KW - Ultraviolet Rays -- adverse effects KW - Environmental Exposure -- adverse effects KW - Cosmetics -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67780398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+epidemiology&rft.atitle=Test-retest+of+self-reported+exposure+to+artificial+tanning+devices%2C+self-tanning+creams%2C+and+sun+sensitivity+showed+consistency.&rft.au=Beane+Freeman%2C+Laura+E%3BDennis%2C+Leslie+K%3BLynch%2C+Charles+F%3BLowe%2C+John+B%3BClarke%2C+William+R&rft.aulast=Beane+Freeman&rft.aufirst=Laura&rft.date=2005-04-01&rft.volume=58&rft.issue=4&rft.spage=430&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+epidemiology&rft.issn=08954356&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-14 N1 - Date created - 2005-05-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Complementary and alternative medicine patients are talking about: lycopene. AN - 67777694; 15853167 JF - Clinical journal of oncology nursing AU - Lee, Colleen O AD - Office of Cancer Complementary and Alternative Medicine at the National Cancer Institute in Bethesda, MD, USA. leeco@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 245 EP - 246 VL - 9 IS - 2 SN - 1092-1095, 1092-1095 KW - Anticarcinogenic Agents KW - 0 KW - Antioxidants KW - Carotenoids KW - 36-88-4 KW - lycopene KW - SB0N2N0WV6 KW - Nursing KW - United States KW - Patient Education as Topic KW - Evidence-Based Medicine KW - Drug Interactions KW - United States Food and Drug Administration KW - Humans KW - Prostatic Neoplasms -- prevention & control KW - Dietary Supplements KW - Patient Acceptance of Health Care -- psychology KW - Male KW - Carotenoids -- therapeutic use KW - Anticarcinogenic Agents -- therapeutic use KW - Complementary Therapies -- standards KW - Complementary Therapies -- psychology KW - Antioxidants -- therapeutic use KW - Complementary Therapies -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67777694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+journal+of+oncology+nursing&rft.atitle=Complementary+and+alternative+medicine+patients+are+talking+about%3A+lycopene.&rft.au=Lee%2C+Colleen+O&rft.aulast=Lee&rft.aufirst=Colleen&rft.date=2005-04-01&rft.volume=9&rft.issue=2&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Clinical+journal+of+oncology+nursing&rft.issn=10921095&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-26 N1 - Date created - 2005-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Focal adhesion kinase as a potential target in arsenic toxicity. AN - 67751814; 15834968 JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Liu, Jie AU - Waalkes, Michael AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, 111 Alexander Drive, Research Triangle Park, North Carolina 27709, USA. Liu6@niehs.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 212 EP - 213 VL - 84 IS - 2 SN - 1096-6080, 1096-6080 KW - Arsenites KW - 0 KW - Enzyme Inhibitors KW - Sodium Compounds KW - sodium arsenite KW - 48OVY2OC72 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 - Arsenic KW - N712M78A8G KW - Index Medicus KW - Myoblasts -- enzymology KW - Myoblasts -- pathology KW - Myoblasts -- drug effects KW - Humans KW - Enzyme Inhibitors -- toxicity KW - Arsenites -- toxicity KW - Sodium Compounds -- toxicity KW - Cell Movement -- drug effects KW - Cell Line KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Arsenic Poisoning -- enzymology KW - Arsenic -- toxicity KW - Protein-Tyrosine Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67751814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Focal+adhesion+kinase+as+a+potential+target+in+arsenic+toxicity.&rft.au=Liu%2C+Jie%3BWaalkes%2C+Michael&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2005-04-01&rft.volume=84&rft.issue=2&rft.spage=212&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 - 2005-07-11 N1 - Date created - 2005-04-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Toxicol Sci. 2005 Apr;84(2):278-86 [15537746] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of the epidermal growth factor receptor increases expression of genes that stimulate inflammation, apoptosis, and cell attachment. AN - 67738391; 15827339 AB - The epidermal growth factor receptor (EGFR) is overexpressed in several types of human cancer, and inhibition of EGFR function is a promising strategy for cancer therapy. We used cDNA microarrays to examine alterations in gene expression after treatment of carcinoma cells with PD153035, a specific and reversible inhibitor of EGFR function. When human cervical carcinoma cells were grown on a collagen substrate in three-dimensional organotypic culture, untreated cells expressed high levels of EGFR RNA and invaded the underlying collagen. Blocking EGFR function decreased DNA synthesis and inhibited invasion in a dose-dependent manner. Microarray analyses identified 312 genes that were significantly increased or decreased in expression after EGFR inhibition. Many could be classified into one of four functional groups including genes that (a) stimulate inflammation and innate immunity, (b) promote cell attachment, (c) enhance apoptosis, and (d) inhibit cell cycle progression. PD153035 induced a dose-dependent activation of nuclear factor kappaB, a transcription factor that stimulates proinflammatory gene expression. Our results identify alterations in gene expression caused by EGFR inhibition and show that this response varies significantly in different cell lines. JF - Molecular cancer therapeutics AU - Woodworth, Craig D AU - Michael, Evan AU - Marker, Dan AU - Allen, Sarah AU - Smith, Laura AU - Nees, Matthias AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland, USA. woodworth@clarkson.edu Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 650 EP - 658 VL - 4 IS - 4 SN - 1535-7163, 1535-7163 KW - 4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline KW - 0 KW - Antineoplastic Agents KW - DNA, Complementary KW - Enzyme Inhibitors KW - NF-kappa B KW - Oligonucleotide Probes KW - Quinazolines KW - Tyrosine KW - 42HK56048U KW - RNA KW - 63231-63-0 KW - Collagen KW - 9007-34-5 KW - DNA KW - 9007-49-2 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Apoptosis KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Nucleic Acid Hybridization KW - Collagen -- chemistry KW - Down-Regulation KW - Phosphorylation KW - RNA -- metabolism KW - Genes, Reporter KW - DNA -- chemistry KW - Oligonucleotide Probes -- chemistry KW - Gene Expression Regulation KW - Cell Cycle KW - Dose-Response Relationship, Drug KW - Immunoprecipitation KW - Cell Line, Tumor KW - Inflammation KW - Tyrosine -- chemistry KW - Polymerase Chain Reaction KW - Bromodeoxyuridine -- pharmacology KW - Blotting, Western KW - Uterine Cervical Neoplasms -- drug therapy KW - DNA, Complementary -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - RNA -- chemistry KW - Up-Regulation KW - Antineoplastic Agents -- pharmacology KW - Quinazolines -- pharmacology KW - Female KW - NF-kappa B -- metabolism KW - Gene Expression Regulation, Neoplastic KW - Receptor, Epidermal Growth Factor -- antagonists & inhibitors KW - Receptor, Epidermal Growth Factor -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67738391?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+the+epidermal+growth+factor+receptor+increases+expression+of+genes+that+stimulate+inflammation%2C+apoptosis%2C+and+cell+attachment.&rft.au=Woodworth%2C+Craig+D%3BMichael%2C+Evan%3BMarker%2C+Dan%3BAllen%2C+Sarah%3BSmith%2C+Laura%3BNees%2C+Matthias&rft.aulast=Woodworth&rft.aufirst=Craig&rft.date=2005-04-01&rft.volume=4&rft.issue=4&rft.spage=650&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 - 2005-10-06 N1 - Date created - 2005-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of risk factors for nasopharyngeal carcinoma in high-risk nasopharyngeal carcinoma families in Taiwan. AN - 67736591; 15826929 AB - A study of nasopharyngeal carcinoma (NPC) families with two or more affected members was conducted in Taiwan (265 families with 2,444 individuals, 502 affected and 1,942 unaffected) to determine the association between NPC and potential etiologic factors in NPC high-risk families. Similar to results from a previous case-control study in Taiwan, Guangdong salted fish consumption during childhood, exposure to wood, and betel nut consumption were all associated with elevated NPC risk using conditional logistic regression, although these associations were not as strong as in the case-control study possibly due to shared environment among family members. Risk associated with cumulative wood exposure and salted fish consumption before age 10 was stronger in families with early NPC age-onset [odds ratio (OR(wood)), 5.10; 95% confidence interval (95% CI), 1.50-17.34; OR(fish), 3.94; 95% CI, 1.47-10.55] or three or more affected members (OR(wood), 4.41; 95% CI, 1.58-12.30; OR(fish), 4.27; 95% CI, 1.10-16.47). In contrast, a tendency for elevated risk was noted for betel nut use in late age-onset families (OR, 2.44; 95% CI, 1.16-5.13) and the CYP2E1 c2 allele in families with less than three affected members (OR, 2.06; 95% CI, 1.04-3.35). Risk estimates associated with these exposures were similar when the analyses were restricted to EBV-seropositive subjects. To better adjust for degree of relationship among family members and residual genetic correlations, we also calculated ORs using a variance components model. The results from the two methods were similar indicating that the risk estimates from conditional logistic regression were unbiased. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Yang, Xiaohong Rose AU - Diehl, Scott AU - Pfeiffer, Ruth AU - Chen, Chien-Jen AU - Hsu, Wan-Lun AU - Dosemeci, Mustafa AU - Cheng, Yu-Juen AU - Sun, Brenda AU - Goldstein, Alisa M AU - Hildesheim, Allan AU - Chinese and American Genetic Epidemiology of NPC Study Team AD - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Room 7014, Bethesda, MD 20852, USA. royang@mail.nih.gov ; Chinese and American Genetic Epidemiology of NPC Study Team Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 900 EP - 905 VL - 14 IS - 4 SN - 1055-9965, 1055-9965 KW - Index Medicus KW - Epidemiologic Methods KW - Humans KW - Child KW - Genotype KW - Registries KW - Logistic Models KW - Risk Factors KW - Taiwan -- epidemiology KW - Adult KW - Surveys and Questionnaires KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Nasopharyngeal Neoplasms -- etiology KW - Diet KW - Nasopharyngeal Neoplasms -- genetics KW - Environmental Exposure -- adverse effects KW - Areca -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67736591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evaluation+of+risk+factors+for+nasopharyngeal+carcinoma+in+high-risk+nasopharyngeal+carcinoma+families+in+Taiwan.&rft.au=Yang%2C+Xiaohong+Rose%3BDiehl%2C+Scott%3BPfeiffer%2C+Ruth%3BChen%2C+Chien-Jen%3BHsu%2C+Wan-Lun%3BDosemeci%2C+Mustafa%3BCheng%2C+Yu-Juen%3BSun%2C+Brenda%3BGoldstein%2C+Alisa+M%3BHildesheim%2C+Allan%3BChinese+and+American+Genetic+Epidemiology+of+NPC+Study+Team&rft.aulast=Yang&rft.aufirst=Xiaohong&rft.date=2005-04-01&rft.volume=14&rft.issue=4&rft.spage=900&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 - 2005-06-28 N1 - Date created - 2005-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Linking the ubiquitin-proteasome pathway to chromatin remodeling/modification by nuclear receptors. AN - 67731431; 15821097 AB - Over 25 years ago, eukaryotic cells were shown to contain a highly specific system for the selective degradation of short-lived proteins, this system is known as the ubiquitin-proteasome pathway. In this pathway, proteins are targeted for degradation by covalent modification by a small highly conserved protein named ubiquitin. Ubiquitin-mediated degradation of regulatory proteins plays an important role in numerous cell processes, including cell cycle progression, signal transduction and transcriptional regulation. Recent experiments have shown that the ubiquitin-proteasome pathway is also involved in nuclear hormone receptor (NR)-mediated transcriptional regulation. The idea that the ubiquitin-proteasome pathway is involved in NR-mediated transcription is strengthened by experiments showing that ubiquitin-proteasome components are recruited to NR target gene promoters. However, it is not clear how these components modulate NR-mediated chromatin remodeling and gene expression. In this review, we postulate the role of the ubiquitin-proteasome pathway on NR-mediated chromatin remodeling and gene regulation based on the current knowledge from studies implicating the pathway in chromatin structure modifications that are applicable to NR function. Since evidence from this laboratory, using the glucocorticoid receptor responsive mouse mammary tumor virus (MMTV) promoter organized as chromatin, suggest that the ubiquitin-proteasome system may be involved in the elongation phase of transcription, we particularly concentrate on chromatin modifications associated with the elongation phase. JF - Journal of molecular endocrinology AU - Kinyamu, H K AU - Chen, J AU - Archer, T K AD - Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 281 EP - 297 VL - 34 IS - 2 SN - 0952-5041, 0952-5041 KW - Chromatin KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Ubiquitin KW - RNA Polymerase II KW - EC 2.7.7.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - RNA Polymerase II -- metabolism KW - Animals KW - Transcription, Genetic KW - Gene Expression Regulation KW - Nucleic Acid Conformation KW - Signal Transduction -- physiology KW - Ubiquitin -- metabolism KW - Chromatin -- metabolism KW - Proteasome Endopeptidase Complex -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Chromatin Assembly and Disassembly KW - Chromatin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67731431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrical+Journal&rft.atitle=Quantifying+the+Magnitude+of+Baseline+Covariate+Imbalances+Resulting+from+Selection+Bias+in+Randomized+Clinical+Trials&rft.au=Berger%2C+Vance+W&rft.aulast=Berger&rft.aufirst=Vance&rft.date=2005-04-01&rft.volume=47&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200410106 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-22 N1 - Date created - 2005-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - The biology of tobacco and nicotine: bench to bedside. AN - 67726665; 15824140 AB - Strong epidemiologic evidence links smoking and cancer. An increased understanding of the molecular biology of tobacco-related cancers could advance progress toward improving smoking cessation and patient management. Knowledge gaps between tobacco addiction, tumorigenesis, and cancer brought an interdisciplinary group of investigators together to discuss "The Biology of Nicotine and Tobacco: Bench to Bedside." Presentations on the signaling pathways and pathogenesis in tobacco-related cancers, mouse models of addiction, imaging and regulation of nicotinic receptors, the genetic basis for tobacco carcinogenesis and development of lung cancer, and molecular mechanisms of carcinogenesis were heard. Importantly, new opportunities to use molecular biology to identify and abrogate tobacco-mediated carcinogenesis and to identify high-risk individuals were recognized. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Dennis, Phillip A AU - Van Waes, Carter AU - Gutkind, J Silvio AU - Kellar, Kenneth J AU - Vinson, Charles AU - Mukhin, Alexey G AU - Spitz, Margaret R AU - Bailey-Wilson, Joan E AU - Yeh, Grace Chao AU - Anderson, Lucy M AU - Wiest, Jonathan S Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 764 EP - 767 VL - 14 IS - 4 KW - NF-kappa B KW - 0 KW - Receptors, Nicotinic KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Animals KW - Molecular Biology KW - Risk Factors KW - Humans KW - Nicotine -- adverse effects KW - Smoking -- adverse effects KW - Receptors, Nicotinic -- drug effects KW - Neoplasms -- prevention & control KW - NF-kappa B -- physiology KW - Neoplasms -- genetics KW - Neoplasms -- etiology KW - NF-kappa B -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67726665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&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=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=The+biology+of+tobacco+and+nicotine%3A+bench+to+bedside.&rft.au=Dennis%2C+Phillip+A%3BVan+Waes%2C+Carter%3BGutkind%2C+J+Silvio%3BKellar%2C+Kenneth+J%3BVinson%2C+Charles%3BMukhin%2C+Alexey+G%3BSpitz%2C+Margaret+R%3BBailey-Wilson%2C+Joan+E%3BYeh%2C+Grace+Chao%3BAnderson%2C+Lucy+M%3BWiest%2C+Jonathan+S&rft.aulast=Dennis&rft.aufirst=Phillip&rft.date=2005-04-01&rft.volume=14&rft.issue=4&rft.spage=764&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 - 2005-06-28 N1 - Date created - 2005-04-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Hum Genet. 2004 Sep;75(3):460-74 [15272417] J Natl Cancer Inst. 1963 Feb;30:289-312 [13985327] Am J Med. 1975 Jul;59(1):145-51 [806230] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIV & psychiatric disorders. AN - 67716617; 15817956 AB - HIV infection and psychiatric disorders have a complex relationship. Being HIV infected could result in psychiatric disorders as a psychological consequence of the infection or because of the effect of the HIV virus on the brain. Disorders may be as varied as depression, post-traumatic stress disorders, AIDS phobias, grief and the whole gamut of cognitive disorders. In addition, several psychiatric conditions may predispose individuals to acquiring HIV infection as a consequence of their influence on behaviour. There is also strong evidence of the relationship of substance use disorders and severe mental illnesses with HIV infection. HIV related psychiatric disorders also offer a challenge to clinicians in issues of differential diagnosis and management. Majority of the work in India has focused on substance use and HIV, and to a lesser extent on the psychiatric effects of HIV infection. Given the magnitude of the problem in the country and the multiple physical and psychological stressors that persons with HIV face in India, more research is needed. JF - The Indian journal of medical research AU - Chandra, Prabha S AU - Desai, Geetha AU - Ranjan, Sanjeev AD - Department of Psychiatry, National Institute of Mental Health & Neurosciences, Bangalore 560 029, India. prabhachandra@rediffmail.com Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 451 EP - 467 VL - 121 IS - 4 SN - 0971-5916, 0971-5916 KW - Anti-HIV Agents KW - 0 KW - Psychotropic Drugs KW - Index Medicus KW - Humans KW - Cognition Disorders -- drug therapy KW - Psychotropic Drugs -- therapeutic use KW - Anti-HIV Agents -- adverse effects KW - Quality of Life KW - Substance-Related Disorders -- complications KW - Cognition Disorders -- complications KW - HIV Infections -- complications KW - Mental Disorders -- drug therapy KW - HIV Infections -- drug therapy KW - Mental Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67716617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Indian+journal+of+medical+research&rft.atitle=HIV+%26amp%3B+psychiatric+disorders.&rft.au=Chandra%2C+Prabha+S%3BDesai%2C+Geetha%3BRanjan%2C+Sanjeev&rft.aulast=Chandra&rft.aufirst=Prabha&rft.date=2005-04-01&rft.volume=121&rft.issue=4&rft.spage=451&rft.isbn=&rft.btitle=&rft.title=The+Indian+journal+of+medical+research&rft.issn=09715916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-05 N1 - Date created - 2005-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Agrobacterium tumefaciens-mediated transformation of Aspergillus fumigatus: an efficient tool for insertional mutagenesis and targeted gene disruption. AN - 67708552; 15812003 AB - Agrobacterium tumefaciens was used to transform Aspergillus fumigatus by either random or site-directed integration of transforming DNA (T-DNA). Random mutagenesis via Agrobacterium tumefaciens-mediated transformation (ATMT) was accomplished with T-DNA containing a hygromycin resistance cassette. Cocultivation of A. fumigatus conidia and Agrobacterium (1:10 ratio) for 48 h at 24 degrees C resulted in high frequencies of transformation (> 100 transformants/10(7) conidia). The majority of transformants harbored a randomly integrated single copy of T-DNA and were mitotically stable. We chose alb1, a polyketide synthase gene, as the target gene for homologous integration because of the clear phenotype difference between the white colonies of Deltaalb1 mutant strains and the bluish-green colonies of wild-type strains. ATMT with a T-DNA-containing alb1 disruption construct resulted in 66% albino transformants. Southern analysis revealed that 19 of the 20 randomly chosen albino transformants (95%) were disrupted by homologous recombination. These results suggest that ATMT is an efficient tool for transformation, random insertional mutagenesis, and gene disruption in A. fumigatus. JF - Applied and environmental microbiology AU - Sugui, Janyce A AU - Chang, Yun C AU - Kwon-Chung, K J AD - Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 1798 EP - 1802 VL - 71 IS - 4 SN - 0099-2240, 0099-2240 KW - Polyketide Synthases KW - 79956-01-7 KW - Index Medicus KW - Polyketide Synthases -- genetics KW - Humans KW - Mutagenesis, Insertional KW - Gene Deletion KW - Agrobacterium tumefaciens -- genetics KW - Transformation, Bacterial KW - Aspergillus fumigatus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67708552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+and+environmental+microbiology&rft.atitle=Agrobacterium+tumefaciens-mediated+transformation+of+Aspergillus+fumigatus%3A+an+efficient+tool+for+insertional+mutagenesis+and+targeted+gene+disruption.&rft.au=Sugui%2C+Janyce+A%3BChang%2C+Yun+C%3BKwon-Chung%2C+K+J&rft.aulast=Sugui&rft.aufirst=Janyce&rft.date=2005-04-01&rft.volume=71&rft.issue=4&rft.spage=1798&rft.isbn=&rft.btitle=&rft.title=Applied+and+environmental+microbiology&rft.issn=00992240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-06 N1 - Date created - 2005-04-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Biotechnol. 1998 Sep;16(9):839-42 [9743116] J Bacteriol. 1998 Jun;180(12):3031-8 [9620950] Nat Biotechnol. 1999 Jun;17(6):598-601 [10385327] J Bacteriol. 2001 Dec;183(23):6852-61 [11698374] Annu Rev Microbiol. 2002;56:433-55 [12142473] Microbiol Mol Biol Rev. 2003 Mar;67(1):16-37, table of contents [12626681] Infect Immun. 2003 May;71(5):2819-26 [12704156] Curr Genet. 2003 Aug;43(5):371-7 [12756496] Fungal Genet Biol. 2003 Aug;39(3):264-75 [12892639] Curr Genet. 2004 Feb;45(1):54-60 [14586554] Gene. 1987;56(1):117-24 [2824287] EMBO J. 1995 Jul 3;14(13):3206-14 [7621833] Methods Mol Biol. 1995;55:63-72 [8528423] J Bacteriol. 1996 Mar;178(6):1498-504 [8626274] Clin Infect Dis. 1998 Apr;26(4):781-803; quiz 804-5 [9564455] Med Microbiol Immunol. 1998 Oct;187(2):79-89 [9832321] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects on alcohol related fatal crashes of a community based initiative to increase substance abuse treatment and reduce alcohol availability. AN - 67699911; 15805436 AB - This analysis tested whether comprehensive community interventions that focus on reducing alcohol availability and increasing substance abuse treatment can reduce alcohol related fatal traffic crashes. Five of 14 communities awarded Fighting Back grants by The Robert Wood Johnson Foundation to reduce substance abuse and related problems attempted to reduce availability of alcohol and expand substance abuse treatment programs (FBAT communities). Program implementation began on 1 January 1992. A quasi-experimental design matched each program community to two or three other communities of similar demographic composition in the same state. The ratio of fatal crashes involving a driver or pedestrian with a blood alcohol concentration of 0.01% or higher, 0.08% or higher, or 0.15% or higher were examined relative to fatal crashes where no alcohol was involved for 10 years preceding and 10 years following program initiation. Relative to their comparison communities, the five FBAT communities experienced significant declines of 22% in alcohol related fatal crashes at 0.01% BAC or higher, 20% at 0.08% or higher, and 17% at 0.15% or higher relative to fatal crashes not involving alcohol. Community interventions to reduce alcohol availability and increase substance abuse treatment can reduce alcohol related fatal traffic crashes. JF - Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention AU - Hingson, R W AU - Zakocs, R C AU - Heeren, T AU - Winter, M R AU - Rosenbloom, D AU - DeJong, W AD - Boston University School of Public Health, Center to Prevent Alcohol-related Problems Among Young People, Boston, MA 02118, USA. rhingson@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 84 EP - 90 VL - 11 IS - 2 SN - 1353-8047, 1353-8047 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - United States KW - Ethanol -- blood KW - Program Evaluation -- methods KW - Humans KW - Alcoholic Beverages -- supply & distribution KW - Automobile Driving KW - Accidents, Traffic -- mortality KW - Community Health Services -- methods KW - Accidents, Traffic -- trends KW - Consumer Advocacy KW - Alcohol-Related Disorders -- prevention & control KW - Alcohol Drinking -- prevention & control KW - Accidents, Traffic -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67699911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Injury+prevention+%3A+journal+of+the+International+Society+for+Child+and+Adolescent+Injury+Prevention&rft.atitle=Effects+on+alcohol+related+fatal+crashes+of+a+community+based+initiative+to+increase+substance+abuse+treatment+and+reduce+alcohol+availability.&rft.au=Hingson%2C+R+W%3BZakocs%2C+R+C%3BHeeren%2C+T%3BWinter%2C+M+R%3BRosenbloom%2C+D%3BDeJong%2C+W&rft.aulast=Hingson&rft.aufirst=R&rft.date=2005-04-01&rft.volume=11&rft.issue=2&rft.spage=84&rft.isbn=&rft.btitle=&rft.title=Injury+prevention+%3A+journal+of+the+International+Society+for+Child+and+Adolescent+Injury+Prevention&rft.issn=13538047&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-05 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Consult Clin Psychol. 1999 Dec;67(6):989-94 [10596521] Alcohol Alcohol. 1999 Jul-Aug;34(4):609-21 [10456590] Inj Prev. 2000 Jun;6(2):109-14 [10875666] JAMA. 2000 Nov 8;284(18):2341-7 [11066184] Am J Prev Med. 2001 Nov;21(4 Suppl):66-88 [11691562] J Stud Alcohol. 2001 Nov;62(6):806-16 [11838918] J Stud Alcohol Suppl. 2002 Mar;(14):226-40 [12022727] Ann Intern Med. 2004 Apr 6;140(7):557-68 [15068985] Traffic Inj Prev. 2004 Sep;5(3):220-7 [15276922] Traffic Inj Prev. 2004 Sep;5(3):278-91 [15276929] Alcohol Res Health. 2003;27(1):63-78 [15301401] J Pediatr. 2004 Sep;145(3):396-402 [15343198] Lancet. 2004 Oct 9-15;364(9442):1334-9 [15474136] Control Clin Trials. 1986 Sep;7(3):177-88 [3802833] Issues Sci Technol. 1991 Summer;7(4):78-84 [10170798] Bull N Y Acad Med. 1994 Summer;71(1):111-35 [8069272] Addiction. 1995 Jul;90(7):907-26 [7663313] Am J Public Health. 1996 Jun;86(6):791-7 [8659651] Addiction. 2000 Feb;95(2):209-17 [10723849] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BLM helicase facilitates Mus81 endonuclease activity in human cells. AN - 67698358; 15805243 AB - Bloom syndrome is a rare, autosomal recessive inherited disorder in humans. The product of the Bloom syndrome mutated gene, designated BLM, is a member of the RecQ helicase family. BLM has been proposed to function at the interface of replication and recombination, and to facilitate the repair of DNA damage. Here, we report in vivo physical interaction and colocalization of BLM and a DNA structure-specific endonuclease, Mus81, at sites of stalled replication forks outside the promyelocytic leukemia nuclear bodies during the S-phase arrest of the cell cycle. Amino acids 125 to 244 of Mus81 interact with the C-terminal region (amino acids 1,007-1,417) of BLM. Whereas Mus81 does not have any effect on the helicase activity of BLM, BLM can stimulate Mus81 endonuclease activity on the nicked Holliday junctions and 3' flap. This stimulation is due to enhanced binding of Mus81 to the DNA substrates. These data suggest a new function of BLM in cooperating with Mus81 during processing and restoration of stalled replication forks. JF - Cancer research AU - Zhang, Ran AU - Sengupta, Sagar AU - Yang, Qin AU - Linke, Steven P AU - Yanaihara, Nozomu AU - Bradsher, John AU - Blais, Veronique AU - McGowan, Clare H AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 2526 EP - 2531 VL - 65 IS - 7 SN - 0008-5472, 0008-5472 KW - DNA-Binding Proteins KW - 0 KW - DNA KW - 9007-49-2 KW - Endonucleases KW - EC 3.1.- KW - MUS81 protein, human 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 - Index Medicus KW - Fibroblasts -- enzymology KW - Peptide Mapping KW - Transfection KW - Humans KW - DNA -- metabolism KW - DNA Replication -- physiology KW - HCT116 Cells KW - DNA -- biosynthesis KW - Cell Line KW - Binding Sites KW - Endonucleases -- metabolism KW - DNA Helicases -- metabolism KW - DNA-Binding Proteins -- genetics KW - DNA Helicases -- genetics KW - Adenosine Triphosphatases -- metabolism KW - Endonucleases -- genetics KW - Adenosine Triphosphatases -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67698358?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=BLM+helicase+facilitates+Mus81+endonuclease+activity+in+human+cells.&rft.au=Zhang%2C+Ran%3BSengupta%2C+Sagar%3BYang%2C+Qin%3BLinke%2C+Steven+P%3BYanaihara%2C+Nozomu%3BBradsher%2C+John%3BBlais%2C+Veronique%3BMcGowan%2C+Clare+H%3BHarris%2C+Curtis+C&rft.aulast=Zhang&rft.aufirst=Ran&rft.date=2005-04-01&rft.volume=65&rft.issue=7&rft.spage=2526&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 - 2005-05-26 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: an extended follow-up. AN - 67569412; 15800318 AB - Many children diagnosed with retinoblastoma (Rb) survive into adulthood and are prone to subsequent cancers, particularly hereditary patients, who have germline Rb-1 mutations. We have extended the follow-up of a large cohort of Rb patients for 7 more years to provide new information on the risk of additional cancers after radiotherapy in long-term survivors. We analyzed the risk of new cancers through 2000 in 1,601 Rb survivors, diagnosed from 1914 to 1984, at two US medical centers. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cancers after hereditary and nonhereditary Rb to the expected number from the Connecticut Tumor Registry. The cumulative incidence of a new cancer after hereditary and nonhereditary Rb and radiotherapy was calculated with adjustment for competing risk of death. Subsequent cancer risk in 963 hereditary patients (SIR, 19; 95% CI, 16 to 21) exceeded the risk in 638 nonhereditary Rb patients (SIR, 1.2; 95% CI, 0.7 to 2.0). Radiation further increased the risk of another cancer in hereditary patients by 3.1-fold (95% CI, 2.0 to 5.3). Hereditary patients continued to be at significantly increased risk for sarcomas, melanoma, and cancers of the brain and nasal cavities. The cumulative incidence for developing a new cancer at 50 years after diagnosis of Rb was 36% (95% CI, 31% to 41%) for hereditary and 5.7% (95% CI, 2.4% to 11%) for nonhereditary patients. Hereditary Rb predisposes to a variety of new cancers over time, with radiotherapy further enhancing the risk of tumors arising in the radiation field. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Kleinerman, Ruth A AU - Tucker, Margaret A AU - Tarone, Robert E AU - Abramson, David H AU - Seddon, Johanna M AU - Stovall, Marilyn AU - Li, Frederick P AU - Fraumeni, Joseph F AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD 20852-7362, USA. Kleinerr@mail.nih.gov Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 2272 EP - 2279 VL - 23 IS - 10 SN - 0732-183X, 0732-183X KW - Index Medicus KW - Nasal Cavity KW - Skin Neoplasms -- etiology KW - Brachytherapy -- adverse effects KW - Humans KW - Melanoma -- etiology KW - Child KW - Child, Preschool KW - Infant KW - Nose Neoplasms -- etiology KW - Incidence KW - Follow-Up Studies KW - Sarcoma -- etiology KW - Female KW - Male KW - Retinal Neoplasms -- genetics KW - Neoplasms, Radiation-Induced -- etiology KW - Registries -- statistics & numerical data KW - Retinoblastoma -- genetics KW - Retinal Neoplasms -- radiotherapy KW - Retinoblastoma -- radiotherapy KW - Genetic Predisposition to Disease KW - Survivors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67569412?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Risk+of+new+cancers+after+radiotherapy+in+long-term+survivors+of+retinoblastoma%3A+an+extended+follow-up.&rft.au=Kleinerman%2C+Ruth+A%3BTucker%2C+Margaret+A%3BTarone%2C+Robert+E%3BAbramson%2C+David+H%3BSeddon%2C+Johanna+M%3BStovall%2C+Marilyn%3BLi%2C+Frederick+P%3BFraumeni%2C+Joseph+F&rft.aulast=Kleinerman&rft.aufirst=Ruth&rft.date=2005-04-01&rft.volume=23&rft.issue=10&rft.spage=2272&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 - 2005-04-21 N1 - Date created - 2005-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. AN - 67567850; 15800326 AB - We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma. Thirty-five patients with metastatic melanoma, all but one with disease refractory to treatment with high-dose interleukin (IL) -2 and many with progressive disease after chemotherapy, underwent lymphodepleting conditioning with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine (25 mg/m(2)). On the day following the final dose of fludarabine, all patients received cell infusion with autologous tumor-reactive, rapidly expanded tumor infiltrating lymphocyte cultures and high-dose IL-2 therapy. Eighteen (51%) of 35 treated patients experienced objective clinical responses including three ongoing complete responses and 15 partial responses with a mean duration of 11.5 +/- 2.2 months. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of treatment included the expected hematologic toxicities of chemotherapy including neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one patient who developed an Epstein-Barr virus-related lymphoproliferation. Lymphodepleting chemotherapy followed by the transfer of highly avid antitumor lymphocytes can mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Dudley, Mark E AU - Wunderlich, John R AU - Yang, James C AU - Sherry, Richard M AU - Topalian, Suzanne L AU - Restifo, Nicholas P AU - Royal, Richard E AU - Kammula, Udai AU - White, Don E AU - Mavroukakis, Sharon A AU - Rogers, Linda J AU - Gracia, Gerald J AU - Jones, Stephanie A AU - Mangiameli, David P AU - Pelletier, Michelle M AU - Gea-Banacloche, Juan AU - Robinson, Michael R AU - Berman, David M AU - Filie, Armando C AU - Abati, Andrea AU - Rosenberg, Steven A AD - Surgery Branch, National Cancer Institute, NIH, CRC 3-3940, 10 Center Dr MSC 1201, Bethesda MD 20892-1202, USA. Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 2346 EP - 2357 VL - 23 IS - 10 SN - 0732-183X, 0732-183X KW - Interleukin-2 KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Interleukin-2 -- pharmacology KW - Humans KW - Disease Progression KW - Aged KW - Child KW - Drug Resistance, Neoplasm KW - Adult KW - Treatment Outcome KW - Neoplasm Metastasis KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Vidarabine -- analogs & derivatives KW - Adoptive Transfer KW - Skin Neoplasms -- immunology KW - Skin Neoplasms -- therapy KW - Melanoma -- therapy KW - Vidarabine -- administration & dosage KW - Melanoma -- immunology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Lymphocytes, Tumor-Infiltrating UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67567850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Adoptive+cell+transfer+therapy+following+non-myeloablative+but+lymphodepleting+chemotherapy+for+the+treatment+of+patients+with+refractory+metastatic+melanoma.&rft.au=Dudley%2C+Mark+E%3BWunderlich%2C+John+R%3BYang%2C+James+C%3BSherry%2C+Richard+M%3BTopalian%2C+Suzanne+L%3BRestifo%2C+Nicholas+P%3BRoyal%2C+Richard+E%3BKammula%2C+Udai%3BWhite%2C+Don+E%3BMavroukakis%2C+Sharon+A%3BRogers%2C+Linda+J%3BGracia%2C+Gerald+J%3BJones%2C+Stephanie+A%3BMangiameli%2C+David+P%3BPelletier%2C+Michelle+M%3BGea-Banacloche%2C+Juan%3BRobinson%2C+Michael+R%3BBerman%2C+David+M%3BFilie%2C+Armando+C%3BAbati%2C+Andrea%3BRosenberg%2C+Steven+A&rft.aulast=Dudley&rft.aufirst=Mark&rft.date=2005-04-01&rft.volume=23&rft.issue=10&rft.spage=2346&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 - 2005-04-21 N1 - Date created - 2005-03-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunother. 2003 Sep-Oct;26(5):385-93 [12973027] Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1969-74 [14762166] J Immunol. 2004 May 15;172(10):6057-64 [15128789] J Immunol. 1980 Aug;125(2):711-4 [6156213] J Exp Med. 1982 Apr 1;155(4):1063-74 [6460831] J Exp Med. 1982 Aug 1;156(2):385-97 [6980254] Science. 1986 Sep 19;233(4770):1318-21 [3489291] J Immunol Methods. 1990 Apr 17;128(2):189-201 [1691237] J Exp Med. 1994 Jul 1;180(1):347-52 [7516411] J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66 [8028037] J Immunol. 1995 Apr 15;154(8):3961-8 [7706734] Int J Cancer. 1996 Feb 8;65(4):413-21 [8621219] Int J Cancer. 1998 Feb 9;75(4):517-24 [9466650] Immunol Rev. 1997 Dec;160:91-102 [9476668] J Exp Med. 1998 Jul 20;188(2):277-86 [9670040] Science. 2002 Oct 25;298(5594):850-4 [12242449] Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2982-7 [10077623] Cancer. 1999 Feb 25;87(1):37-42 [10096358] J Exp Med. 2003 Aug 18;198(4):569-80 [12925674] Nat Rev Cancer. 2003 Sep;3(9):666-75 [12951585] J Immunol. 2005 Mar 1;174(5):2591-601 [15728465] Eur J Immunol. 2003 Aug;33(8):2123-32 [12884286] Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8372-7 [12826605] J Immunother. 2003 Jul-Aug;26(4):332-42 [12843795] Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16168-73 [12427970] Blood. 2002 Dec 1;100(12):3877-86 [12433695] Blood. 2002 Oct 1;100(7):2562-71 [12239170] J Immunother. 2002 May-Jun;25(3):243-51 [12000866] J Immunother. 2001 Jul-Aug;24(4):363-73 [11565838] J Clin Oncol. 2001 Aug 1;19(15):3477-82 [11481353] Cancer J Sci Am. 2000 Feb;6 Suppl 1:S11-4 [10685652] Blood. 2000 Apr 1;95(7):2269-74 [10733495] N Engl J Med. 2000 Sep 14;343(11):750-8 [10984562] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The mitotic chromosome binding activity of the papillomavirus E2 protein correlates with interaction with the cellular chromosomal protein, Brd4. AN - 67564681; 15795266 AB - The papillomavirus transcriptional activator, E2, is involved in key functions of the viral life cycle. These include transcriptional regulation, viral DNA replication, and viral genome segregation. The transactivation domain of E2 is required for each of these functions. To identify the regions of the domain that mediate binding to mitotic chromosomes, a panel of mutations has been generated and their effect on various E2 functions has been analyzed. A structural model of the bovine papillomavirus type 1 (BPV1) E2 transactivation domain was generated based on its homology with the solved structure of the human papillomavirus type 16 (HPV16) domain. This model was used to identify distinct surfaces of the domain to be targeted by point mutation to further delineate the functional region of the transactivation domain responsible for mitotic chromosome association. The mutated E2 proteins were assessed for mitotic chromosome binding and, in addition, transcriptional activation and transcriptional repression activities. Mutation of amino acids R37 and I73, which are located on a surface of the domain that in HPV16 E2 is reported to mediate self-interaction, completely eliminated mitotic chromosome binding. Mitotic chromosome binding activity was found to correlate well with the ability to interact with the cellular chromosomal associated factor Brd4, which has recently been proposed to mediate the association between BPV1 E2 and mitotic chromosomes. JF - Journal of virology AU - Baxter, Michael K AU - McPhillips, Maria G AU - Ozato, Keiko AU - McBride, Alison A AD - Laboratory of Viral Diseases, NIAID, NIH, Building 4, Room 137, 4 Center Dr., MSC 0455, Bethesda, MD 20892-0455, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 4806 EP - 4818 VL - 79 IS - 8 SN - 0022-538X, 0022-538X KW - BRD4 protein, human KW - 0 KW - DNA-Binding Proteins KW - E2 protein, Bovine papillomavirus KW - Nuclear Proteins KW - Oncogene Proteins, Fusion KW - Oncogene Proteins, Viral KW - Recombinant Proteins KW - Transcription Factors KW - Viral Proteins KW - oncogene protein E2, Human papillomavirus type 1 KW - Index Medicus KW - Animals KW - HeLa Cells KW - Models, Molecular KW - Humans KW - Viral Proteins -- chemistry KW - Transcriptional Activation KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Oncogene Proteins, Fusion -- chemistry KW - Oncogene Proteins, Fusion -- genetics KW - Viral Proteins -- metabolism KW - Oncogene Proteins, Fusion -- metabolism KW - Chromosomes, Human -- genetics KW - DNA Replication KW - Protein Conformation KW - Cell Division KW - DNA-Binding Proteins -- chemistry KW - Oncogene Proteins, Viral -- chemistry KW - Mitosis -- genetics KW - DNA-Binding Proteins -- genetics KW - Oncogene Proteins, Viral -- genetics KW - Oncogene Proteins, Viral -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67564681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+mitotic+chromosome+binding+activity+of+the+papillomavirus+E2+protein+correlates+with+interaction+with+the+cellular+chromosomal+protein%2C+Brd4.&rft.au=Baxter%2C+Michael+K%3BMcPhillips%2C+Maria+G%3BOzato%2C+Keiko%3BMcBride%2C+Alison+A&rft.aulast=Baxter&rft.aufirst=Michael&rft.date=2005-04-01&rft.volume=79&rft.issue=8&rft.spage=4806&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 - 2005-05-17 N1 - Date created - 2005-03-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Gen Virol. 2002 Jan;83(Pt 1):179-88 [11752715] Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2998-3003 [15710895] Mol Cell Biol. 2002 Sep;22(18):6509-20 [12192049] J Virol. 2002 Nov;76(21):10914-20 [12368334] J Virol. 2003 Jun;77(12):6946-56 [12768013] Cell Mol Life Sci. 2003 Apr;60(4):721-41 [12785719] Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8758-63 [12840145] J Virol. 2004 Feb;78(4):2100-13 [14747575] J Biol Chem. 2004 Feb 20;279(8):6976-85 [14634007] Cell. 2004 Apr 30;117(3):349-60 [15109495] Genes Dev. 2004 Aug 15;18(16):1981-96 [15289463] Cell. 1985 Aug;42(1):183-91 [2990724] Nature. 1987 Dec 17-23;330(6149):670-2 [3317067] EMBO J. 1987 Nov;6(11):3391-7 [2828029] Acta Med Okayama. 1988 Aug;42(4):243-5 [2845712] EMBO J. 1988 Dec 1;7(12):3807-16 [2850174] Proc Natl Acad Sci U S A. 1989 Jan;86(2):510-4 [2536165] Genes Dev. 1989 Jan;3(1):38-48 [2540059] J Virol. 1989 Dec;63(12):5076-85 [2555544] EMBO J. 1991 Feb;10(2):449-57 [1846806] Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3204-8 [1849647] J Virol. 1991 Oct;65(10):5314-22 [1654443] EMBO J. 1991 Dec;10(13):4321-9 [1661672] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5086-90 [8389467] J Virol. 1993 Jul;67(7):3720-9 [8389903] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7051-5 [8041744] J Virol. 1995 Oct;69(10):6199-208 [7666521] J Virol. 1995 Dec;69(12):7791-9 [7494290] J Virol. 1996 Jan;70(1):23-9 [8523530] J Biol Chem. 1995 Dec 29;270(52):30914-8 [8537346] EMBO J. 1996 Jan 2;15(1):1-11 [8598191] J Virol. 1996 Mar;70(3):1602-11 [8627680] J Virol. 1996 Jul;70(7):4193-9 [8676438] Virology. 1996 Jul 1;221(1):34-43 [8661412] Virology. 1996 Jul 1;221(1):44-53 [8661413] J Virol. 2002 Nov;76(21):11042-53 [12368347] J Virol. 2002 Nov;76(22):11596-604 [12388720] J Virol. 1999 Dec;73(12):9789-95 [10559289] Nature. 2000 Feb 17;403(6771):805-9 [10693813] J Virol. 2000 Apr;74(8):3752-60 [10729150] Virology. 2000 Apr 25;270(1):124-34 [10772985] J Virol. 2000 Jul;74(13):5872-9 [10846067] Mol Cell Biol. 2000 Sep;20(17):6537-49 [10938129] Virology. 2000 Oct 25;276(2):304-14 [11040122] Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12513-8 [11070078] EMBO J. 2001 Jan 15;20(1-2):222-30 [11226172] Mol Cell Biol. 2001 May;21(10):3576-88 [11313483] Front Biosci. 2001 Aug 1;6:D1008-18 [11487468] J Virol. 1996 Sep;70(9):6169-79 [8709243] J Biol Chem. 1997 Nov 21;272(47):29873-9 [9368061] J Virol. 1998 Mar;72(3):2079-88 [9499063] Virology. 1998 Feb 15;241(2):312-22 [9499806] Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4338-43 [9539738] J Virol. 1998 May;72(5):3925-34 [9557678] J Mol Biol. 1998 Jul 3;280(1):1-9 [9653027] J Virol. 1999 Apr;73(4):2587-95 [10074103] J Virol. 1999 May;73(5):4385-92 [10196336] J Virol. 1999 May;73(5):4404-12 [10196338] Mol Cell Biol. 1999 May;19(5):3349-59 [10207059] J Virol. 2005 Feb;79(3):1500-9 [15650176] Virology. 2005 Feb 5;332(1):78-88 [15661142] J Virol. 2002 Mar;76(5):2480-90 [11836426] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Convection perfusion of glucocerebrosidase for neuronopathic Gaucher's disease. AN - 67557889; 15786474 AB - Systemic enzyme replacement for Gaucher's disease has not prevented premature death or severe morbidity in patients with a neuronopathic phenotype, because the enzyme does not cross the blood-brain barrier. We used convection-enhanced delivery for regional distribution of glucocerebrosidase in rat and primate brains and examined its safety and feasibility for neuronopathic Gaucher's disease. Rats underwent intrastriatal infusion and were observed and then sacrificed at 14 hours, 4 days, or 6 weeks. Primates underwent serial magnetic resonance imaging during enzyme perfusion of the right frontal lobe or brainstem, were observed and then sacrificed after infusion completion. Animals underwent histologic and enzymatic tissue analyses. Magnetic resonance imaging revealed perfusion of the primate right frontal lobe or pons with infusate. Enzyme activity was substantially and significantly (p < 0.05) increased in cortex and white matter of the infused frontal lobe and pons compared to control. Immunohistochemistry demonstrated intraneuronal glucocerebrosidase. There was no toxicity. Convection-enhanced delivery can be used to safely perfuse large regions of the brain and brainstem with therapeutic levels of glucocerebrosidase. Patients with neuronopathic Gaucher's disease and similar central nervous system disorders may benefit from this treatment. JF - Annals of neurology AU - Lonser, Russell R AU - Walbridge, Stuart AU - Murray, Gary J AU - Aizenberg, Michele R AU - Vortmeyer, Alexander O AU - Aerts, Johannes M F G AU - Brady, Roscoe O AU - Oldfield, Edward H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. lonserr@ninds.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 542 EP - 548 VL - 57 IS - 4 SN - 0364-5134, 0364-5134 KW - Glucosylceramidase KW - EC 3.2.1.45 KW - Index Medicus KW - Rats KW - Magnetic Resonance Imaging KW - Animals KW - Perfusion -- methods KW - Macaca mulatta KW - Immunohistochemistry KW - Male KW - Convection KW - Brain -- enzymology KW - Glucosylceramidase -- administration & dosage KW - Glucosylceramidase -- metabolism KW - Gaucher Disease -- drug therapy KW - Drug Delivery Systems -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67557889?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+neurology&rft.atitle=Convection+perfusion+of+glucocerebrosidase+for+neuronopathic+Gaucher%27s+disease.&rft.au=Lonser%2C+Russell+R%3BWalbridge%2C+Stuart%3BMurray%2C+Gary+J%3BAizenberg%2C+Michele+R%3BVortmeyer%2C+Alexander+O%3BAerts%2C+Johannes+M+F+G%3BBrady%2C+Roscoe+O%3BOldfield%2C+Edward+H&rft.aulast=Lonser&rft.aufirst=Russell&rft.date=2005-04-01&rft.volume=57&rft.issue=4&rft.spage=542&rft.isbn=&rft.btitle=&rft.title=Annals+of+neurology&rft.issn=03645134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-20 N1 - Date created - 2005-03-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Secondary structure and gating rearrangements of transmembrane segments in rat P2X4 receptor channels. AN - 67556651; 15795310 AB - P2X receptors are cation selective channels that are activated by extracellular nucleotides. These channels are likely formed by three identical or related subunits, each having two transmembrane segments (TM1 and TM2). To identify regions that undergo rearrangement during gating and to probe their secondary structure, we performed tryptophan scanning mutagenesis on the two putative TMs of the rat P2X4 receptor channel. Mutant channels were expressed in Xenopus oocytes, concentration-response relationships constructed for ATP, and the EC50 estimated by fitting the Hill equation to the data. Of the 22 mutations in TM1 and 24 in TM2, all but one in TM1 and seven in TM2 result in functional channels. Interestingly, the majority of the functional mutants display an increased sensitivity to ATP, and in general these perturbations are more pronounced for TM2 when compared with TM1. For TM1 and for the outer half of TM2, the perturbations are consistent with these regions adopting alpha-helical secondary structures. In addition, the greatest perturbations in the gating equilibrium occur for mutations near the outer ends of both TM1 and TM2. Surface biotinylation experiments reveal that all the nonfunctional mutants traffic to the surface membrane at levels comparable to the WT channel, suggesting that these mutations likely disrupt ion conduction or gating. Taken together, these results suggest that the outer parts of TM1 and TM2 are helical and that they move during activation. The observation that the majority of nonconducting mutations are clustered toward the inner end of TM2 suggests a critical functional role for this region. JF - The Journal of general physiology AU - Silberberg, Shai D AU - Chang, Tsg-Hui AU - Swartz, Kenton J AD - Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. silberbs@ninds.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 347 EP - 359 VL - 125 IS - 4 SN - 0022-1295, 0022-1295 KW - P2rx4 protein, rat KW - 0 KW - Receptors, Purinergic P2 KW - Receptors, Purinergic P2X4 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Xenopus laevis KW - Animals KW - Protein Structure, Secondary KW - Molecular Sequence Data KW - Oocytes -- physiology KW - Amino Acid Sequence KW - Amino Acid Substitution KW - Structure-Activity Relationship KW - Ion Channel Gating -- physiology KW - Models, Molecular KW - Receptors, Purinergic P2 -- chemistry KW - Cell Membrane -- chemistry KW - Models, Chemical KW - Cell Membrane -- physiology KW - Models, Biological KW - Receptors, Purinergic P2 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67556651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+general+physiology&rft.atitle=Secondary+structure+and+gating+rearrangements+of+transmembrane+segments+in+rat+P2X4+receptor+channels.&rft.au=Silberberg%2C+Shai+D%3BChang%2C+Tsg-Hui%3BSwartz%2C+Kenton+J&rft.aulast=Silberberg&rft.aufirst=Shai&rft.date=2005-04-01&rft.volume=125&rft.issue=4&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+general+physiology&rft.issn=00221295&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-27 N1 - Date created - 2005-03-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 2001 May 4;276(18):14902-8 [11278888] J Neurosci. 2001 Aug 15;21(16):5885-92 [11487611] J Biol Chem. 2001 Aug 17;276(33):30934-41 [11402044] J Biol Chem. 2001 Aug 31;276(35):32793-8 [11438537] Neuron. 2001 Nov 20;32(4):649-56 [11719205] Nature. 2002 Jan 17;415(6869):287-94 [11796999] Mol Pharmacol. 2002 Feb;61(2):303-11 [11809854] Annu Rev Biophys Biomol Struct. 2002;31:207-33 [11988468] J Gen Physiol. 2002 Jun;119(6):521-32 [12034760] J Gen Physiol. 2002 Jun;119(6):581-91 [12034765] Nature. 2002 May 30;417(6888):515-22 [12037559] Nature. 2002 May 30;417(6888):523-6 [12037560] Physiol Rev. 2002 Oct;82(4):1013-67 [12270951] Neuropharmacology. 2002 Sep;43(4):669-78 [12367612] Nat Neurosci. 1999 Apr;2(4):322-30 [10204538] Mol Pharmacol. 1999 Nov;56(5):973-81 [10531403] Cell. 2002 Oct 18;111(2):231-9 [12408867] Neuron. 2003 Apr 10;38(1):61-7 [12691664] Nature. 2003 May 1;423(6935):33-41 [12721618] Science. 2003 Jun 20;300(5627):1922-6 [12738871] Sci STKE. 2003 Jun 24;2003(188):re10 [12824476] Nature. 2003 Jun 26;423(6943):949-55 [12827192] J Neurosci. 2003 Oct 1;23(26):8903-10 [14523092] Biochemistry. 2003 Oct 28;42(42):12243-50 [14567686] J Gen Physiol. 2003 Nov;122(5):541-56 [14557403] J Gen Physiol. 2004 Mar;123(3):281-93 [14769846] J Biol Chem. 2004 Mar 5;279(10):9043-55 [14699168] J Neurosci. 2004 Mar 31;24(13):3413-20 [15056721] Nature. 2004 Apr 22;428(6985):864-8 [15103379] Nat Struct Mol Biol. 2004 Jun;11(6):499-501 [15164005] Trends Neurosci. 2004 Jun;27(6):321-8 [15165736] Trends Neurosci. 2004 Jun;27(6):329-36 [15165737] J Mol Biol. 2004 Sep 3;342(1):333-43 [15313628] J Neurosci. 2004 Aug 18;24(33):7378-86 [15317863] J Gen Physiol. 2004 Oct;124(4):319-32 [15365093] J Mol Biol. 1987 Jun 5;195(3):659-85 [3656427] Proc Natl Acad Sci U S A. 1988 Dec;85(23):9012-6 [3057498] Science. 1989 Aug 4;245(4917):510-3 [2667138] Annu Rev Biochem. 1989;58:607-33 [2673018] Neuron. 1992 Nov;9(5):861-71 [1419000] Nature. 1994 Oct 6;371(6497):516-9 [7523951] Nature. 1994 Oct 6;371(6497):519-23 [7523952] Neuron. 1995 Jun;14(6):1293-301 [7605638] Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12046-9 [8618841] Biophys J. 1997 Apr;72(4):1489-500 [9083655] Proc Natl Acad Sci U S A. 1997 May 13;94(10):5456-60 [9144259] Nature. 1997 Jun 5;387(6633):624-7 [9177353] EMBO J. 1997 Jun 16;16(12):3446-54 [9218787] J Neurosci. 1998 Apr 1;18(7):2350-9 [9502796] Biochem Biophys Res Commun. 1998 Mar 17;244(2):599-603 [9514958] J Gen Physiol. 1999 Mar;113(3):415-23 [10051517] Nat Neurosci. 1999 Apr;2(4):315-21 [10204537] J Gen Physiol. 2000 Jan;115(1):33-50 [10613917] J Gen Physiol. 2000 Jan;115(1):51-8 [10613918] Neuron. 2000 Feb;25(2):411-23 [10719895] Biochemistry. 2000 Apr 25;39(16):4666-73 [10769122] J Biol Chem. 2000 Sep 22;275(38):29361-7 [10827197] J Biol Chem. 2000 Nov 3;275(44):34190-6 [10940304] J Gen Physiol. 2001 Mar;117(3):205-18 [11222625] J Gen Physiol. 2001 Apr;117(4):345-60 [11279254] Neuron. 2001 Mar;29(3):657-67 [11301025] Science. 1998 Apr 3;280(5360):69-77 [9525859] EMBO J. 1998 Jun 1;17(11):3016-28 [9606184] J Biol Chem. 1998 Jun 12;273(24):15177-82 [9614131] Eur J Pharmacol. 1998 Apr 17;347(1):141-4 [9650860] Science. 1998 Dec 18;282(5397):2220-6 [9856938] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Needs and opportunities for research in hypersensitivity pneumonitis. AN - 67556038; 15657460 AB - Hypersensitivity pneumonitis (HP) develops after inhalation of many different environmental antigens, causing variable clinical symptoms that often make diagnosis uncertain. The prevalence of HP is higher than recognized, especially its chronic form. Mechanisms of disease are still incompletely known. Strategies to improve detection and diagnosis are needed, and treatment options, principally avoidance, are limited. A workshop recommended: a population-based study to more accurately document the incidence and prevalence of HP; better classification of disease stages, including natural history; evaluation of diagnostic tests and biomarkers used to detect disease; better correlation of computerized tomography lung imaging and pathologic changes; more study of inflammatory and immune mechanisms; and improvement of animal models that are more relevant for human disease. JF - American journal of respiratory and critical care medicine AU - Fink, Jordan N AU - Ortega, Hector G AU - Reynolds, Herbert Y AU - Cormier, Yvon F AU - Fan, Leland L AU - Franks, Teri J AU - Kreiss, Kathleen AU - Kunkel, Steven AU - Lynch, David AU - Quirce, Santiago AU - Rose, Cecile AU - Schleimer, Robert P AU - Schuyler, Mark R AU - Selman, Moises AU - Trout, Douglas AU - Yoshizawa, Yasuyuki AD - DLD/NHLBI, Two Rockledge Center, 6701 Rockledge Drive, Bethesda, MD 20892-7952, USA. Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 792 EP - 798 VL - 171 IS - 7 SN - 1073-449X, 1073-449X KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Animals KW - Health Services Needs and Demand KW - Humans KW - Tomography, X-Ray Computed KW - Prognosis KW - Disease Models, Animal KW - Child KW - Mice KW - Child, Preschool KW - Risk Assessment KW - Adult KW - Occupational Exposure -- adverse effects KW - Environmental Exposure -- adverse effects KW - Research -- trends KW - Alveolitis, Extrinsic Allergic -- etiology KW - Alveolitis, Extrinsic Allergic -- epidemiology KW - Alveolitis, Extrinsic Allergic -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67556038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Needs+and+opportunities+for+research+in+hypersensitivity+pneumonitis.&rft.au=Fink%2C+Jordan+N%3BOrtega%2C+Hector+G%3BReynolds%2C+Herbert+Y%3BCormier%2C+Yvon+F%3BFan%2C+Leland+L%3BFranks%2C+Teri+J%3BKreiss%2C+Kathleen%3BKunkel%2C+Steven%3BLynch%2C+David%3BQuirce%2C+Santiago%3BRose%2C+Cecile%3BSchleimer%2C+Robert+P%3BSchuyler%2C+Mark+R%3BSelman%2C+Moises%3BTrout%2C+Douglas%3BYoshizawa%2C+Yasuyuki&rft.aulast=Fink&rft.aufirst=Jordan&rft.date=2005-04-01&rft.volume=171&rft.issue=7&rft.spage=792&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 - 2005-06-08 N1 - Date created - 2005-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regions of the varicella-zoster virus open reading frame 63 latency-associated protein important for replication in vitro are also critical for efficient establishment of latency. AN - 67554177; 15795292 AB - Varicella-zoster virus (VZV) open reading frame 63 (ORF63) is one of the most abundant transcripts expressed during VZV latency in humans, and ORF63 protein has been detected in human ganglia by several laboratories. Deletion of over 90% of the ORF63 gene showed that the protein is required for efficient establishment of latency in rodents. We have constructed viruses with a series of mutations in ORF63. While prior experiments showed that transfection of cells with a plasmid expressing ORF63 but lacking the putative nuclear localization signal of the protein resulted in increased expression of the protein in the cytoplasm, we found that ORF63 protein remained in the nucleus in cells infected with a VZV ORF63 nuclear localization signal deletion mutant. This mutant was not impaired for growth in cell culture or for latency in rodents. Replacement of five serine or threonine phosphorylation sites in ORF63 with alanines resulted in a virus that was impaired for replication in vitro and for latency. A series of ORF63 carboxy-terminal mutants showed that the last 70 amino acids do not affect replication in vitro or latency in rodents; however, the last 108 amino acids are important for replication and latency. Thus, regions of ORF63 that are important for replication in vitro are also required for efficient establishment of latency. JF - Journal of virology AU - Cohen, Jeffrey I AU - Krogmann, Tammy AU - Bontems, Sebastien AU - Sadzot-Delvaux, Catherine AU - Pesnicak, Lesley AD - Laboratory of Clinical Infectious Diseases, Bldg. 10, Room 11N228, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892, USA. jcohen@niaid.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 5069 EP - 5077 VL - 79 IS - 8 SN - 0022-538X, 0022-538X KW - Immediate-Early Proteins KW - 0 KW - Viral Envelope Proteins KW - immediate early protein 63, Human herpesvirus 3 KW - Index Medicus KW - Animals KW - Cell Nucleus -- virology KW - Humans KW - Transcription, Genetic KW - Cell Line, Tumor KW - Cosmids KW - Sigmodontinae KW - Cloning, Molecular KW - Melanoma KW - Mutagenesis KW - Ganglia -- virology KW - Phosphorylation KW - Restriction Mapping KW - Herpesvirus 3, Human -- growth & development KW - Virus Latency -- genetics KW - Herpesvirus 3, Human -- genetics KW - Virus Replication -- genetics KW - Immediate-Early Proteins -- genetics KW - Open Reading Frames -- genetics KW - Herpesvirus 3, Human -- physiology KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67554177?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Regions+of+the+varicella-zoster+virus+open+reading+frame+63+latency-associated+protein+important+for+replication+in+vitro+are+also+critical+for+efficient+establishment+of+latency.&rft.au=Cohen%2C+Jeffrey+I%3BKrogmann%2C+Tammy%3BBontems%2C+Sebastien%3BSadzot-Delvaux%2C+Catherine%3BPesnicak%2C+Lesley&rft.aulast=Cohen&rft.aufirst=Jeffrey&rft.date=2005-04-01&rft.volume=79&rft.issue=8&rft.spage=5069&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 - 2005-05-17 N1 - Date created - 2005-03-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2122-4 [8700895] J Virol. 1996 May;70(5):2789-96 [8627753] Virology. 1998 Jul 5;246(2):306-16 [9657949] Virology. 1999 Jun 5;258(2):451-4 [10366583] J Virol. 2000 Dec;74(24):11464-71 [11090142] J Virol. 2000 Dec;74(24):11893-8 [11090189] J Virol. 2001 Sep;75(17):8224-39 [11483768] J Virol. 2001 Sep;75(18):8854-8 [11507231] Virology. 2001 Oct 25;289(2):218-23 [11689044] J Biol Chem. 2002 Jun 7;277(23):21050-60 [11912195] J Virol. 2002 Nov;76(21):11012-23 [12368344] Virology. 2002 Oct 10;302(1):71-82 [12429517] J Virol. 2003 Jun;77(12):6660-5 [12767985] J Virol. 2003 Oct;77(20):11180-5 [14512565] J Virol. 2004 Feb;78(3):1181-94 [14722273] J Virol. 2004 Nov;78(21):11833-40 [15479825] J Gen Virol. 1986 Sep;67 ( Pt 9):1759-816 [3018124] Virology. 1993 Mar;193(1):193-200 [7679857] Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7376-80 [8394020] J Virol. 1995 Jan;69(1):476-91 [7983744] J Virol. 1995 May;69(5):3240-5 [7707559] J Virol. 1995 Jul;69(7):4274-82 [7769688] J Virol. 1995 Nov;69(11):7367-70 [7474171] J Virol. 1996 Jan;70(1):658-62 [8523589] J Virol. 1996 Feb;70(2):1050-60 [8551563] Neurology. 1995 Dec;45(12 Suppl 8):S18-20 [8545010] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):7080-5 [9618542] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy and safety of generic amphotericin B in experimental pulmonary aspergillosis. AN - 67553699; 15793161 AB - The recent shortage of the brand name drug Fungizone has necessitated a change to generic formulations of amphotericin B deoxycholate. Clinical trials cannot be conducted in a timely manner to provide data on the safety and efficacy of these formulations. We therefore compared generic amphotericin B and Fungizone for activity and safety in the treatment of experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits. Fungizone and generic amphotericin B are similar in efficacy, pharmacokinetics, and safety in the treatment of experimental IPA. JF - Antimicrobial agents and chemotherapy AU - Petraitis, Vidmantas AU - Petraitiene, Ruta AU - Lin, Pengxin AU - Calis, Karim AU - Kelaher, Amy M AU - Muray, Heidi A AU - Mya-San, Christine AU - Mickiene, Diana AU - Bacher, John AU - Walsh, Thomas J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Building 10, CRC, Rm. 1W-5740, 10 Center Dr., MSC 1100, Bethesda, Maryland 20892-1100, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 1642 EP - 1645 VL - 49 IS - 4 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Drugs, Generic KW - Amphotericin B KW - 7XU7A7DROE KW - Index Medicus KW - Animals KW - Neutropenia -- complications KW - Rabbits KW - Antifungal Agents -- adverse effects KW - Lung Diseases, Fungal -- drug therapy KW - Drugs, Generic -- therapeutic use KW - Drugs, Generic -- adverse effects KW - Aspergillosis -- drug therapy KW - Amphotericin B -- adverse effects KW - Amphotericin B -- therapeutic use KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67553699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Efficacy+and+safety+of+generic+amphotericin+B+in+experimental+pulmonary+aspergillosis.&rft.au=Petraitis%2C+Vidmantas%3BPetraitiene%2C+Ruta%3BLin%2C+Pengxin%3BCalis%2C+Karim%3BKelaher%2C+Amy+M%3BMuray%2C+Heidi+A%3BMya-San%2C+Christine%3BMickiene%2C+Diana%3BBacher%2C+John%3BWalsh%2C+Thomas+J&rft.aulast=Petraitis&rft.aufirst=Vidmantas&rft.date=2005-04-01&rft.volume=49&rft.issue=4&rft.spage=1642&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 - 2005-05-12 N1 - Date created - 2005-03-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Pharmacotherapy. 2003 May;23(5):572-8 [12741430] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] Infect Dis Clin North Am. 1989 Sep;3(3):641-51 [2671144] Chemotherapy. 1989;35(5):320-5 [2791709] Clin Infect Dis. 1992 Mar;14 Suppl 1:S43-53 [1562695] Cancer. 1992 Jun 1;69(11):2653-62 [1315207] Clin Microbiol Infect. 2001;7 Suppl 2:25-31 [11525215] J Infect. 1996 Jul;33(1):23-32 [8842991] J Clin Microbiol. 1997 Jan;35(1):139-43 [8968895] J Infect Dis. 1997 Jun;175(6):1459-66 [9180187] Clin Microbiol Rev. 1999 Apr;12(2):310-50 [10194462] J Infect Dis. 2000 Jul;182(1):274-82 [10882607] J Infect Dis. 1994 Feb;169(2):356-68 [8106769] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. AN - 67553696; 15791003 AB - A growing body of evidence indicates that an inflammatory process in the substantia nigra, characterized by activation of resident microglia, likely either initiates or aggravates nigral neurodegeneration in Parkinson's disease (PD). To study the mechanisms by which nigral microglia are activated in PD, the potential role of alpha-synuclein (a major component of Lewy bodies that can cause neurodegeneration when aggregated) in microglial activation was investigated. The results demonstrated that in a primary mesencephalic neuron-glia culture system, extracellular aggregated human alpha-synuclein indeed activated microglia; microglial activation enhanced dopaminergic neurodegeneration induced by aggregated alpha-synuclein. Furthermore, microglial enhancement of alpha-synuclein-mediated neurotoxicity depended on phagocytosis of alpha-synuclein and activation of NADPH oxidase with production of reactive oxygen species. These results suggest that nigral neuronal damage, regardless of etiology, may release aggregated alpha-synuclein into substantia nigra, which activates microglia with production of proinflammatory mediators, thereby leading to persistent and progressive nigral neurodegeneration in PD. Finally, NADPH oxidase could be an ideal target for potential pharmaceutical intervention, given that it plays a critical role in alpha-synuclein-mediated microglial activation and associated neurotoxicity. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Zhang, Wei AU - Wang, Tongguang AU - Pei, Zhong AU - Miller, David S AU - Wu, Xuefei AU - Block, Michelle L AU - Wilson, Belinda AU - Zhang, Wanqin AU - Zhou, Yong AU - Hong, Jau-Shyong AU - Zhang, Jing 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 - 2005/04// PY - 2005 DA - April 2005 SP - 533 EP - 542 VL - 19 IS - 6 KW - Nitrites KW - 0 KW - Polymers KW - Reactive Oxygen Species KW - Recombinant Proteins KW - Tumor Necrosis Factor-alpha KW - alpha-Synuclein KW - Tritium KW - 10028-17-8 KW - Nitric Oxide KW - 31C4KY9ESH KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Dinoprostone KW - K7Q1JQR04M KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Nitrites -- analysis KW - NADPH Oxidase -- deficiency KW - Polymers -- pharmacology KW - Humans KW - Dopamine -- physiology KW - Nerve Degeneration -- chemically induced KW - Nitric Oxide -- metabolism KW - Neuroglia -- physiology KW - Mice, Knockout KW - Rats KW - Tyrosine 3-Monooxygenase -- analysis KW - Mesencephalon KW - Rats, Inbred F344 KW - Oxidative Stress KW - Neurons -- physiology KW - NADPH Oxidase -- physiology KW - gamma-Aminobutyric Acid -- metabolism KW - Phagocytosis KW - Embryo, Mammalian KW - Enzyme Activation KW - Brain KW - Astrocytes -- physiology KW - Mice KW - Cells, Cultured KW - Dinoprostone -- metabolism KW - Tumor Necrosis Factor-alpha -- metabolism KW - Immunohistochemistry KW - Substantia Nigra -- metabolism KW - Parkinson Disease -- etiology KW - alpha-Synuclein -- pharmacology KW - Microglia -- physiology KW - alpha-Synuclein -- chemistry KW - alpha-Synuclein -- physiology KW - Microglia -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67553696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Aggregated+alpha-synuclein+activates+microglia%3A+a+process+leading+to+disease+progression+in+Parkinson%27s+disease.&rft.au=Zhang%2C+Wei%3BWang%2C+Tongguang%3BPei%2C+Zhong%3BMiller%2C+David+S%3BWu%2C+Xuefei%3BBlock%2C+Michelle+L%3BWilson%2C+Belinda%3BZhang%2C+Wanqin%3BZhou%2C+Yong%3BHong%2C+Jau-Shyong%3BZhang%2C+Jing&rft.aulast=Zhang&rft.aufirst=Wei&rft.date=2005-04-01&rft.volume=19&rft.issue=6&rft.spage=533&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 - 2005-12-14 N1 - Date created - 2005-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microglial NADPH oxidase is a novel target for femtomolar neuroprotection against oxidative stress. AN - 67553024; 15791005 AB - Inflammation has been increasingly recognized to contribute to the pathogenesis of Parkinson's disease. Several compounds are neuroprotective at femtomolar concentrations through the inhibition of inflammation. However, the mechanisms mediating femtomolar-acting compounds are poorly understood. Here we show that both gly-gly-phe (GGF), a tri-peptide contained in the dynorphin opioid peptide, and naloxone are neuroprotective at femtomolar concentrations against LPS-induced dopaminergic neurotoxicity through the reduction of microglial activation. Mechanistic studies demonstrated the critical role of NADPH oxidase in the GGF and naloxone inhibition of microglial activation and associated DA neurotoxicity. Pharmacophore analysis of the neuroprotective dynorphin peptides and naloxone revealed common chemical properties (hydrogen bond acceptor, hydrogen bond donor, positive ionizable, hydrophobic) of these femtomolar-acting compounds. These results support a common high-affinity site of action for several femtomolar-acting compounds, where NADPH oxidase is the critical mechanism governing neuroprotection, suggesting a novel avenue of anti-inflammatory and neuroprotective therapy. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Qin, Liya AU - Block, Michelle L AU - Liu, Yuxin AU - Bienstock, Rachelle J AU - Pei, Zhong AU - Zhang, Wei AU - Wu, Xuefei AU - Wilson, Belinda AU - Burka, Tom AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 550 EP - 557 VL - 19 IS - 6 KW - Enzyme Inhibitors KW - 0 KW - Lipopolysaccharides KW - Neuroprotective Agents KW - Peptide Fragments KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Superoxides KW - 11062-77-4 KW - Naloxone KW - 36B82AMQ7N KW - Dynorphins KW - 74913-18-1 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Naloxone -- pharmacology KW - Naloxone -- administration & dosage KW - Animals KW - Hydrophobic and Hydrophilic Interactions KW - Naloxone -- chemistry KW - Lipopolysaccharides -- pharmacology KW - Amino Acid Sequence KW - Mice KW - Structure-Activity Relationship KW - Mice, Knockout KW - Rats KW - Superoxides -- metabolism KW - Rats, Inbred F344 KW - Peptide Fragments -- chemistry KW - Dynorphins -- administration & dosage KW - Peptide Fragments -- pharmacology KW - Molecular Sequence Data KW - Dynorphins -- chemistry KW - Mice, Inbred C57BL KW - Enzyme Inhibitors -- pharmacology KW - Tumor Necrosis Factor-alpha -- metabolism KW - Hydrogen Bonding KW - Dynorphins -- pharmacology KW - Microglia -- enzymology KW - NADPH Oxidase -- deficiency KW - NADPH Oxidase -- antagonists & inhibitors KW - Oxidative Stress -- drug effects KW - NADPH Oxidase -- physiology KW - Microglia -- drug effects KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67553024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Microglial+NADPH+oxidase+is+a+novel+target+for+femtomolar+neuroprotection+against+oxidative+stress.&rft.au=Qin%2C+Liya%3BBlock%2C+Michelle+L%3BLiu%2C+Yuxin%3BBienstock%2C+Rachelle+J%3BPei%2C+Zhong%3BZhang%2C+Wei%3BWu%2C+Xuefei%3BWilson%2C+Belinda%3BBurka%2C+Tom%3BHong%2C+Jau-Shyong&rft.aulast=Qin&rft.aufirst=Liya&rft.date=2005-04-01&rft.volume=19&rft.issue=6&rft.spage=550&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 - 2005-12-14 N1 - Date created - 2005-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor necrosis factor enhances SN38-mediated apoptosis in mesothelioma cells: the role of nuclear factor-kappaB pathway activation. AN - 67547722; 15700263 AB - Despite the best and most aggressive, often integrated, standard therapeutic approaches for mesothelioma, overall survival remains very poor. The actual failure points out clearly the need for the development of novel therapy. One of the promising paths of experimentation is artificial induction of apoptosis. A therapeutic strategy that relies on the down-regulation of BCL-XL inhibition nuclear factor kappaB (NF-kappaB) with a combination of SN38 and tumor necrosis factor (TNF) was studied in human mesothelioma cell lines (MSTO-221H, IST-MES1, IST-MES2, MPP89, H28, H513, H2052, and H290). Cell proliferation (clonogenic assay) was inhibited strongly by the combination of TNF and SN38. Examining the persistence of the NF-kappaB complexes using an electrophoretic mobility-shift assay, it appeared that they still were present at 24 hours in TNF-treated cells. In SN38-treated cells, NF-kappaB complexes persisted for 6 hours. In cells that were treated with combined SN38 and TNF, NF-kappaB complexes disappeared quickly and became undetectable at 6 hours. In flow cytometry analysis, only cells that were treated with combined SN38 and TNF demonstrated significant cellular accumulation in the sub-G0-G1 phase, suggesting a specific induction of apoptosis. Morphologic examination (4,6-diamidino-2-phenylindole staining and electron microscopy) and internucleosomal DNA fragmentation (gel ladder) confirmed rigorously the induction of apoptosis. Because of NF-kappaB inhibition with the combination of SN38 and TNF, the expression of BCL-XL (both the protein [Western blot analysis] and the mRNA [reverse transcriptase-polymerase chain reaction analysis]) was down-regulated, cytochrome c was released into the cytoplasm, caspase 3 was activated (Western blot analysis), and, consequently, apoptosis was triggered. The authors hope that the results of the current study may contribute to the design and implementation of a novel therapeutic approach that improves patients' responses to treatment for mesothelioma. Copyright 2005 American Cancer Society. JF - Cancer AU - Russo, Patrizia AU - Catassi, Alessia AU - Malacarne, Davide AU - Margaritora, Stefano AU - Cesario, Alfredo AU - Festi, Luigi AU - Mulé, Antonino AU - Ferri, Luigi AU - Granone, Pierluigi AD - Laboratory of Translational Research B(Lung Cancer), Department of Integrated Medical Oncology, National Cancer Institute, Genoa, Italy. patrizia.russo@istge.it Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 1503 EP - 1518 VL - 103 IS - 7 SN - 0008-543X, 0008-543X KW - BCL2L1 protein, human KW - 0 KW - NF-kappa B KW - Proto-Oncogene Proteins c-bcl-2 KW - Tumor Necrosis Factors KW - bcl-X Protein KW - irinotecan KW - 0H43101T0J KW - Cytochromes c KW - 9007-43-6 KW - Caspases KW - EC 3.4.22.- KW - Camptothecin KW - XT3Z54Z28A KW - Abridged Index Medicus KW - Index Medicus KW - Cytochromes c -- metabolism KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - DNA Damage KW - Humans KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Drug Synergism KW - DNA Fragmentation KW - Cell Cycle -- drug effects KW - Caspases -- metabolism KW - Mesothelioma -- drug therapy KW - Camptothecin -- pharmacology KW - Apoptosis -- drug effects KW - Camptothecin -- analogs & derivatives KW - Tumor Necrosis Factors -- pharmacology KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67547722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+necrosis+factor+enhances+SN38-mediated+apoptosis+in+mesothelioma+cells%3A+the+role+of+nuclear+factor-kappaB+pathway+activation.&rft.au=Russo%2C+Patrizia%3BCatassi%2C+Alessia%3BMalacarne%2C+Davide%3BMargaritora%2C+Stefano%3BCesario%2C+Alfredo%3BFesti%2C+Luigi%3BMul%C3%A9%2C+Antonino%3BFerri%2C+Luigi%3BGranone%2C+Pierluigi&rft.aulast=Russo&rft.aufirst=Patrizia&rft.date=2005-04-01&rft.volume=103&rft.issue=7&rft.spage=1503&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-05 N1 - Date created - 2005-03-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Retraction In: Cancer. 2010 May 1;116(9):2285 [20229574] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Steroid hormone receptor expression and proliferation in rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. AN - 67536030; 15637090 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary gland carcinogen present in the human diet. Herein, the expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ER beta) and progesterone receptor (PR) was examined in mammary gland carcinomas induced by PhIP in female Sprague-Dawley rats. Quantitative real-time polymerase chain reaction demonstrated that ER alpha, ER beta and PR were statistically elevated by 3-, 4- and 8-fold in carcinomas compared with normal mammary glands. By immunohistochemistry, carcinomas showed statistically higher nuclear expression of all three steroid receptors with the majority of carcinomas showing at least 10% of epithelial cells stained for ER alpha (49/55, 89%), ER beta (41/55, 75%) and PR (48/55, 87%). Furthermore, the level of expression of the three steroid hormone receptors was positively correlated with each other across the bank of carcinomas (Spearman analysis, P < 0.05). The expression of ER alpha in carcinomas was associated with tumor grade, extent of nuclear pleomorphism and cellular proliferation as measured by proliferating cell nuclear antigen (PCNA) and phospho-Rb immunostaining (Spearman analysis, P < 0.05). Confocal microscopy was used to measure the percentage of epithelial cells showing nuclear colocalization of receptors, PCNA, and cyclin D1. Colocalization of the receptors, and the colocalization of the receptors with PCNA and cyclin D1 was strikingly higher in carcinomas than in the normal mammary gland. In carcinoma cells, 37% of ER alpha positive epithelial cells were colocalized with PCNA in contrast to just 0.25% of cells in the normal mammary gland. The findings from this study indicate that ER alpha, ER beta and PR were co-upregulated and nuclear localized in epithelial cells from rat mammary carcinomas compared with normal mammary glands, and that the co-upregulation was positively correlated with proliferation and cell cycle progression in carcinomas. JF - Carcinogenesis 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 Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 763 EP - 769 VL - 26 IS - 4 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - Estrogen Receptor alpha KW - Estrogen Receptor beta KW - Imidazoles KW - Proliferating Cell Nuclear Antigen KW - RNA, Messenger KW - Receptors, Progesterone KW - Retinoblastoma Protein KW - Cyclin D1 KW - 136601-57-5 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 909C6UN66T KW - Index Medicus KW - Animals KW - Cell Nucleus -- metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Messenger -- genetics KW - Rats KW - Epithelial Cells -- ultrastructure KW - Rats, Sprague-Dawley KW - Cyclin D1 -- metabolism KW - RNA, Messenger -- metabolism KW - Mammary Glands, Animal -- metabolism KW - Mammary Glands, Animal -- pathology KW - Retinoblastoma Protein -- metabolism KW - Cell Cycle -- drug effects KW - Female KW - Immunoenzyme Techniques KW - Proliferating Cell Nuclear Antigen -- metabolism KW - Receptors, Progesterone -- genetics KW - Cell Proliferation -- drug effects KW - Imidazoles -- toxicity KW - Receptors, Progesterone -- metabolism KW - Estrogen Receptor alpha -- genetics KW - Carcinogens -- toxicity KW - Estrogen Receptor alpha -- metabolism KW - Estrogen Receptor beta -- metabolism KW - Mammary Neoplasms, Experimental -- metabolism KW - Mammary Neoplasms, Experimental -- pathology KW - Estrogen Receptor beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67536030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Steroid+hormone+receptor+expression+and+proliferation+in+rat+mammary+gland+carcinomas+induced+by+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=2005-04-01&rft.volume=26&rft.issue=4&rft.spage=763&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-03 N1 - Date created - 2005-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thrombopoietin alone or in the presence of stem cell factor supports the growth of KIT(CD117)low/ MPL(CD110)+ human mast cells from hematopoietic progenitor cells. AN - 67534240; 15781331 AB - Thrombopoietin (TPO) is known to promote platelet number, have growth-promoting potential for human megakaryocytes (HuMKs), and increase erythrocyte, monocyte, mast cell, and granulocyte numbers in the presence of additional growth factors. We explored the ability of TPO alone or in the presence of stem cell factor (SCF) to support human mast cells (HuMCs). CD34+ pluripotent and CD34+/CD117+/CD13+ HuMC progenitor cells were cultured in rhTPO and examined for HuMCs. Similarly, we added rhTPO to CD34(+) cells cultured in stem cell factor (SCF), which promotes HuMC development. When CD34+ cells were cultured in 10 ng/mL rhTPO and 10 ng/mL rhSCF, TPO enhanced HuMC numbers compared to rhSCF alone. Higher concentrations of rhTPO (50 ng/mL) in the presence of 100 ng/mL rhSCF inhibited the rhSCF-dependent subpopulation of CD117high HuMCs, while promoting CD117low HuMCs. Human CD34+/CD117+/CD13+ cells cultured in rhTPO alone for 1 to 2 weeks differentiated into CD41+/CD110+ HuMKs (85-90%) and FcepsilonRI+/CD117low/CD13+ HuMCs (5-10%). RhTPO-induced HuMCs expressed the TPO (CD110) receptor, tryptase, and chymase and survived when recultured in rhSCF. The effect of TPO on HuMCs in the presence of rhSCF varies, depending on the relative concentration of each growth factor, while TPO alone or in combination with rhSCF supports a unique population of CD117low/CD110+ HuMCs. JF - Experimental hematology AU - Kirshenbaum, Arnold S AU - Akin, Cem AU - Goff, Julie P AU - Metcalfe, Dean D AD - Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1881, USA. Akirshenba@niaid.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 413 EP - 421 VL - 33 IS - 4 SN - 0301-472X, 0301-472X KW - Proto-Oncogene Proteins KW - 0 KW - Receptors, Cytokine KW - Receptors, Thrombopoietin KW - Stem Cell Factor KW - MPL protein, human KW - 143641-95-6 KW - Thrombopoietin KW - 9014-42-0 KW - Proto-Oncogene Proteins c-kit KW - EC 2.7.10.1 KW - Index Medicus KW - Drug Interactions KW - Cells, Cultured KW - Humans KW - Cell Culture Techniques KW - Flow Cytometry KW - Immunophenotyping KW - Cell Proliferation -- drug effects KW - Thrombopoietin -- pharmacology KW - Stem Cell Factor -- pharmacology KW - Hematopoietic Stem Cells -- cytology KW - Mast Cells -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67534240?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+hematology&rft.atitle=Thrombopoietin+alone+or+in+the+presence+of+stem+cell+factor+supports+the+growth+of+KIT%28CD117%29low%2F+MPL%28CD110%29%2B+human+mast+cells+from+hematopoietic+progenitor+cells.&rft.au=Kirshenbaum%2C+Arnold+S%3BAkin%2C+Cem%3BGoff%2C+Julie+P%3BMetcalfe%2C+Dean+D&rft.aulast=Kirshenbaum&rft.aufirst=Arnold&rft.date=2005-04-01&rft.volume=33&rft.issue=4&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=Experimental+hematology&rft.issn=0301472X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-18 N1 - Date created - 2005-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mortality among participants in the agricultural health study. AN - 67534049; 15780775 AB - This analysis of the Agricultural Health Study cohort assesses the mortality experience of licensed pesticide applicators and their spouses. This report is based on 52,393 private applicators (who are mostly farmers) and 32,345 spouses of farmers in Iowa and North Carolina. At enrollment, each pesticide applicator completed a 21-page enrollment questionnaire. Mortality assessment from enrollment (1994-1997) through 2000 provided an average follow-up of about 5.3 years, 447,154 person-years, and 2055 deaths. Compared with the general population in the two states, the cohort experienced a very low mortality rate. Standardized mortality ratios (SMRs) for total mortality, cardiovascular disease, diabetes, COPD, total cancer, and cancers of the esophagus, stomach, and lung were 0.6 or lower for both farmers and spouses. These deficits varied little by farm size, type of crops or livestock on the farm, years of handling pesticides, holding a non-farm job, or length of follow up. SMRs among ever smokers were not as low as among never smokers, but were still less than 1.0 for all smoking-related causes of death. No statistically significant excesses occurred, but slightly elevated SMRs, or those near 1.0, were noted for diseases that have been associated with farming in previous studies. Several factors may contribute to the low mortality observed in this population, including the healthy worker effect typically seen in cohorts of working populations (which may decline in future years), a short follow-up interval, and a healthier lifestyle manifested through lower cigarette use and an occupation that has traditionally required high levels of physical activity. JF - Annals of epidemiology AU - Blair, Aaron AU - Sandler, Dale P AU - Tarone, Robert AU - Lubin, Jay AU - Thomas, Kent AU - Hoppin, Jane A AU - Samanic, Claudine AU - Coble, Joseph AU - Kamel, Freya AU - Knott, Charles AU - Dosemeci, Mustafa AU - Zahm, Shelia Hoar AU - Lynch, Charles F AU - Rothman, Nathaniel AU - Alavanja, Michael C R AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA. blaira@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 279 EP - 285 VL - 15 IS - 4 SN - 1047-2797, 1047-2797 KW - Pesticides KW - 0 KW - Index Medicus KW - Occupational Exposure KW - Humans KW - Cohort Studies KW - Middle Aged KW - North Carolina -- epidemiology KW - Male KW - Iowa -- epidemiology KW - Female KW - Cause of Death KW - Spouses KW - Agriculture KW - Disease -- classification KW - Neoplasms -- classification KW - Neoplasms -- mortality KW - Pesticides -- poisoning KW - Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67534049?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mortality+among+participants+in+the+agricultural+health+study.&rft.au=Blair%2C+Aaron%3BSandler%2C+Dale+P%3BTarone%2C+Robert%3BLubin%2C+Jay%3BThomas%2C+Kent%3BHoppin%2C+Jane+A%3BSamanic%2C+Claudine%3BCoble%2C+Joseph%3BKamel%2C+Freya%3BKnott%2C+Charles%3BDosemeci%2C+Mustafa%3BZahm%2C+Shelia+Hoar%3BLynch%2C+Charles+F%3BRothman%2C+Nathaniel%3BAlavanja%2C+Michael+C+R&rft.aulast=Blair&rft.aufirst=Aaron&rft.date=2005-04-01&rft.volume=15&rft.issue=4&rft.spage=279&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 - 2005-07-05 N1 - Date created - 2005-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular determinants of the agonist binding domain of a P2X receptor channel. AN - 67533877; 15632318 AB - P2 purinergic receptor channel receptors (P2XRs) are a family of ligand-gated cation channels composed of two transmembrane domains, N and C termini located intracellularly, and a large extracellular loop containing the ATP binding domain. To identify regions important for binding and gating, previous experimental work was focused on mutagenesis of conserved ectodomain residues. Here, we used the known sequence and secondary structure similarities between the Lys180-Lys326 ectodomain region of P2X(4) and the class II aminoacyl-tRNA synthetases as a guide to generate a three-dimensional model of the receptor-binding site and to design mutants. The interplay between homology modeling and site-directed mutagenesis suggested that Asp280 residue of P2X(4)R coordinates ATP binding via the magnesium ion, Phe230 residue coordinates the binding of the adenine ring of ATP, and Lys190, His286, and Arg278 residues coordinate the actions of negatively charged alpha-, beta-, and gamma-phosphate groups, respectively. Until the crystal structure of the channel is solved, this model could provide a useful approach for future studies on the identification of ATP binding domain and gating of P2XRs. JF - Molecular pharmacology AU - Yan, Zonghe AU - Liang, Zhaodong AU - Tomic, Melanija AU - Obsil, Tomas AU - Stojilkovic, Stanko S AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development/NIH, Building 49, Room 6A-36, 49 Convent Drive, Bethesda, MD 20892-4510, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 1078 EP - 1088 VL - 67 IS - 4 SN - 0026-895X, 0026-895X KW - Purinergic P2 Receptor Agonists KW - 0 KW - Receptors, Purinergic P2 KW - Receptors, Purinergic P2X KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Models, Molecular KW - Guinea Pigs KW - Cells, Cultured KW - Humans KW - Mice KW - Binding Sites KW - Receptors, Purinergic P2 -- metabolism KW - Receptors, Purinergic P2 -- chemistry KW - Adenosine Triphosphate -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67533877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+determinants+of+the+agonist+binding+domain+of+a+P2X+receptor+channel.&rft.au=Yan%2C+Zonghe%3BLiang%2C+Zhaodong%3BTomic%2C+Melanija%3BObsil%2C+Tomas%3BStojilkovic%2C+Stanko+S&rft.aulast=Yan&rft.aufirst=Zonghe&rft.date=2005-04-01&rft.volume=67&rft.issue=4&rft.spage=1078&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 - 2005-04-20 N1 - Date created - 2005-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Uterine cancer after use of clomiphene citrate to induce ovulation. AN - 67533828; 15781949 AB - Clomiphene citrate, a selective estrogen receptor modulator, increases estradiol levels and consequently may increase risk of cancer of the uterine corpus. The authors conducted a retrospective cohort study of 8,431 US women (145,876 woman-years) evaluated for infertility during 1965-1988. Through 1999, 39 uterine cancers were ascertained by questionnaire or cancer and death registries. Poisson regression estimated adjusted rate ratios. Study results suggest that clomiphene may increase uterine cancer risk (rate ratio (RR) = 1.79, 95% confidence interval (CI): 0.9, 3.4) and present evidence of a dose response (p(trend) = 0.07) and latency effect (p(trend) = 0.04). Uterine cancer risk increased with clomiphene dose (RR = 1.93, 95% CI: 0.9, 4.0 for >900 mg), menstrual cycles of use (RR = 2.16, 95% CI: 0.9, 5.2 for >or=6 cycles), and time elapsed since initial use (RR = 2.50, 95% CI: 0.9, 7.2 for women followed for >or=20 years). Risk was more strongly associated with clomiphene among nulligravid (RR = 3.49, 95% CI: 1.3, 9.3) and obese (RR = 6.02, 95% CI: 1.2, 30.0) women, with risk substantially elevated among women who were both obese and nulligravid (RR = 12.52, 95% CI: 1.5, 108.0). Clomiphene may increase uterine cancer risk, with higher doses leading to higher risk. Long-term follow-up of infertility cohorts is necessary to clarify the association between clomiphene use and uterine cancer. JF - American journal of epidemiology AU - Althuis, Michelle D AU - Moghissi, Kamran S AU - Westhoff, Carolyn L AU - Scoccia, Bert AU - Lamb, Emmet J AU - Lubin, Jay H AU - Brinton, Louise A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7234, USA. m.althuis@verizon.net Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 607 EP - 615 VL - 161 IS - 7 SN - 0002-9262, 0002-9262 KW - Fertility Agents, Female KW - 0 KW - Clomiphene KW - 1HRS458QU2 KW - Index Medicus KW - Infertility, Female -- drug therapy KW - Humans KW - Retrospective Studies KW - Poisson Distribution KW - Risk Assessment KW - Registries KW - Ovulation Induction KW - Adult KW - Surveys and Questionnaires KW - Incidence KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Uterine Neoplasms -- epidemiology KW - Fertility Agents, Female -- therapeutic use KW - Clomiphene -- therapeutic use KW - Uterine Neoplasms -- chemically induced KW - Fertility Agents, Female -- adverse effects KW - Clomiphene -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67533828?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Uterine+cancer+after+use+of+clomiphene+citrate+to+induce+ovulation.&rft.au=Althuis%2C+Michelle+D%3BMoghissi%2C+Kamran+S%3BWesthoff%2C+Carolyn+L%3BScoccia%2C+Bert%3BLamb%2C+Emmet+J%3BLubin%2C+Jay+H%3BBrinton%2C+Louise+A&rft.aulast=Althuis&rft.aufirst=Michelle&rft.date=2005-04-01&rft.volume=161&rft.issue=7&rft.spage=607&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 - 2005-05-12 N1 - Date created - 2005-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insurance coverage, usual source of care, and receipt of clinically indicated care for comorbid conditions among adults living with human immunodeficiency virus. AN - 67532702; 15778643 AB - Associations of insurance coverage and source of care with use of human immunodeficiency virus (HIV)-related health, mental health, and substance abuse services are examined in a large, diverse, highly active antiretroviral therapy-era cohort. Adults who were infected with HIV (n = 3818) were interviewed in clinics and community agencies in Los Angeles, Milwaukee, New York, and San Francisco regarding drug use behaviors, health status, and health care utilization. Most participants were insured by Medicaid. During the previous 3 months, 90% of privately insured, 87% of publicly insured, and 78% of uninsured participants had visited any provider. Publicly and privately insured participants were similar in receipt of antiretrovirals, prophylaxis against Pneumocystis carinii pneumonia, substance abuse services, and antidepressants. Uninsured participants were less likely to receive antiretrovirals but were more likely to use substance abuse services. Participants with no usual source of care were less likely to receive PCP prophylaxis. A lack of insurance is associated with barriers to care, but the advantage of private over public coverage appears smaller than in previous studies. PCP prophylaxis, substance abuse treatment, and antidepressants remain markedly underutilized. Educational initiatives about these treatments targeting providers and patients are indicated. JF - Medical care AU - Goldstein, Risë B AU - Rotheram-Borus, Mary Jane AU - Johnson, Mallory O AU - Weinhardt, Lance S AU - Remien, Robert H AU - Lightfoot, Marguerita AU - Catz, Sheryl L AU - Gore-Felton, Cheryl AU - Kirshenbaum, Sheri AU - Morin, Stephen F AU - NIMH Healthy Living Trial Group AD - Center for Community Health, UCLA Neuropsychiatric Institute, Los Angeles, California, USA. goldster@mail.nih.gov ; NIMH Healthy Living Trial Group Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 401 EP - 410 VL - 43 IS - 4 SN - 0025-7079, 0025-7079 KW - Anti-Retroviral Agents KW - 0 KW - Antidepressive Agents KW - Index Medicus KW - Private Practice -- utilization KW - Health Maintenance Organizations -- utilization KW - Pneumonia, Pneumocystis -- economics KW - Antibiotic Prophylaxis -- utilization KW - Depression -- economics KW - Humans KW - AIDS-Related Opportunistic Infections -- prevention & control KW - Substance-Related Disorders -- economics KW - Anti-Retroviral Agents -- therapeutic use KW - Substance-Related Disorders -- prevention & control KW - Depression -- prevention & control KW - Pneumonia, Pneumocystis -- prevention & control KW - Antiretroviral Therapy, Highly Active -- utilization KW - Adult KW - Depression -- epidemiology KW - Antidepressive Agents -- therapeutic use KW - United States -- epidemiology KW - AIDS-Related Opportunistic Infections -- economics KW - Male KW - Ambulatory Care Facilities -- utilization KW - Female KW - Substance-Related Disorders -- epidemiology KW - HIV Infections -- complications KW - Health Services Accessibility -- economics KW - HIV Infections -- therapy KW - Insurance, Health KW - Health Services -- utilization KW - Medicaid KW - HIV Infections -- economics KW - Insurance Coverage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67532702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diagnostic+Microbiology+and+Infectious+Disease&rft.atitle=Use+of+housekeeping+gene+sequencing+for+species+identification+of+viridans+streptococci&rft.au=Kiratisin%2C+P%3BLi%2C+L%3BMurray%2C+PR%3BFischer%2C+SH&rft.aulast=Kiratisin&rft.aufirst=P&rft.date=2005-04-01&rft.volume=51&rft.issue=4&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=Diagnostic+Microbiology+and+Infectious+Disease&rft.issn=07328893&rft_id=info:doi/10.1016%2Fj.diagmicrobio.2004.12.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-03 N1 - Date created - 2005-03-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. AN - 67529995; 15591121 AB - Regulatory T cells (T(REGs)) control the key aspects of tolerance and play a role in the lack of antitumor immune responses. Cyclophosphamide (CY) is a chemotherapeutic agent with a dose-dependent, bimodal effect on the immune system. Although a previous study demonstrated that CY reduces the number of T(REGs), the mechanism involved in this process has yet to be defined. In this report, it is established that low-dose CY not only decreases cell number but leads to decreased functionality of T(REGs). CY treatment enhances apoptosis and decreases homeostatic proliferation of these cells. Expression of GITR and FoxP3, which are involved in the suppressive activity of T(REGs), is down-regulated after CY administration, though the level of expression varies depending on the time studied. This is the first report demonstrating that CY, in addition to decreasing cell number, inhibits the suppressive capability of T(REGs). The relevance of the loss of suppressor functionality and the changes in gene expression are further discussed. JF - Blood AU - Lutsiak, M E Christine AU - Semnani, Roshanak T AU - De Pascalis, Roberto AU - Kashmiri, Syed V S AU - Schlom, Jeffrey AU - Sabzevari, Helen AD - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg 10, Rm 8B09, Bethesda, MD 20892, USA. Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 2862 EP - 2868 VL - 105 IS - 7 SN - 0006-4971, 0006-4971 KW - Antigens, Surface KW - 0 KW - DNA-Binding Proteins KW - Forkhead Transcription Factors KW - Foxp3 protein, mouse KW - Glucocorticoid-Induced TNFR-Related Protein KW - Immunosuppressive Agents KW - Receptors, Interleukin-2 KW - Receptors, Nerve Growth Factor KW - Receptors, Tumor Necrosis Factor KW - Tnfrsf18 protein, mouse KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Receptors, Nerve Growth Factor -- genetics KW - B-Lymphocytes -- cytology KW - Apoptosis -- immunology KW - DNA-Binding Proteins -- genetics KW - Mice KW - B-Lymphocytes -- immunology KW - Antigens, Surface -- genetics KW - Antigens, Surface -- immunology KW - Cell Differentiation -- immunology KW - B-Lymphocytes -- drug effects KW - Receptors, Interleukin-2 -- metabolism KW - Gene Expression -- immunology KW - Apoptosis -- drug effects KW - Mice, Inbred C57BL KW - Cell Differentiation -- drug effects KW - Receptors, Tumor Necrosis Factor -- genetics KW - Female KW - CD4-Positive T-Lymphocytes -- cytology KW - CD4-Positive T-Lymphocytes -- immunology KW - CD4-Positive T-Lymphocytes -- drug effects KW - Immunosuppressive Agents -- pharmacology KW - Cyclophosphamide -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67529995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+CD4%28%2B%2925%2B+T+regulatory+cell+function+implicated+in+enhanced+immune+response+by+low-dose+cyclophosphamide.&rft.au=Lutsiak%2C+M+E+Christine%3BSemnani%2C+Roshanak+T%3BDe+Pascalis%2C+Roberto%3BKashmiri%2C+Syed+V+S%3BSchlom%2C+Jeffrey%3BSabzevari%2C+Helen&rft.aulast=Lutsiak&rft.aufirst=M+E&rft.date=2005-04-01&rft.volume=105&rft.issue=7&rft.spage=2862&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-03 N1 - Date created - 2005-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine D3 receptor ligands block nicotine-induced conditioned place preferences through a mechanism that does not involve discriminative-stimulus or antidepressant-like effects. AN - 67523833; 15562293 AB - Environmental stimuli previously paired with drug taking appear to play a critical role in nicotine dependence. Converging anatomical, pharmacological, and behavioral evidence implicates dopamine D3 receptors (D3Rs) in the mechanisms underlying stimulus-controlled drug-seeking behavior. This study assessed the effects of BP 897, a D3R partial agonist and ST 198, a D3R antagonist, on nicotine-induced conditioned place preferences (CPPs), used as a measure of drug-seeking behavior, on food-maintained responding and on discrimination performance under a two-lever-choice nicotine discrimination procedure. BP 897 and ST 198 both blocked the expression of nicotine-induced CPP at doses selective for D3R. They had no effect on locomotor activity in the CPP apparatus and no significant effect on nicotine discrimination performance or food-maintained responding under the discrimination procedure. Involvement of antidepressant actions in the effects of BP 897 and ST 198 on CPP is unlikely, since we found no effect of D3R blockade with BP 897 or genetic depletion of D3Rs in a forced swimming test, used as a behavioral test for antidepressant activity. This suggests that D3R ligands reduce the motivational effects of nicotine by a mechanism distinct from those of nicotine replacement therapy and bupropion, the two currently used aids for smoking cessation in humans. These findings support the use of D3R ligands as aids for smoking cessation and indicate that their effects would be selective for those rewarding or reinforcing effects of nicotine that contribute to the maintenance of tobacco-smoking behavior, without affecting subjective responses to nicotine or producing any antidepressant-like effects. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Le Foll, Bernard AU - Sokoloff, Pierre AU - Stark, Holger AU - Goldberg, Steven R AD - Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. blefoll@intra.nida.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 720 EP - 730 VL - 30 IS - 4 SN - 0893-133X, 0893-133X KW - ((E)-N-4-(1,2,3,4-tetrahydroisoquinolin-2-yl)butyl)-3-phenylacrylamide KW - 0 KW - Acrylamides KW - Antidepressive Agents KW - BP 897 KW - Dopamine Agents KW - Dopamine Agonists KW - Dopamine Antagonists KW - Drd3 protein, mouse KW - Drd3 protein, rat KW - Isoquinolines KW - Ligands KW - Piperazines KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D3 KW - Nicotine KW - 6M3C89ZY6R KW - Index Medicus KW - Limbic System -- physiopathology KW - Animals KW - Discrimination (Psychology) -- drug effects KW - Antidepressive Agents -- pharmacology KW - Limbic System -- metabolism KW - Discrimination (Psychology) -- physiology KW - Dopamine Antagonists -- pharmacology KW - Disease Models, Animal KW - Mice KW - Piperazines -- pharmacology KW - Drug Interactions -- physiology KW - Mice, Knockout KW - Conditioning (Psychology) -- drug effects KW - Rats KW - Isoquinolines -- pharmacology KW - Rats, Sprague-Dawley KW - Limbic System -- drug effects KW - Dopamine Agonists -- pharmacology KW - Acrylamides -- pharmacology KW - Conditioning (Psychology) -- physiology KW - Male KW - Female KW - Tobacco Use Disorder -- physiopathology KW - Tobacco Use Disorder -- metabolism KW - Nicotine -- antagonists & inhibitors KW - Spatial Behavior -- drug effects KW - Tobacco Use Disorder -- drug therapy KW - Nicotine -- pharmacology KW - Receptors, Dopamine D2 -- agonists KW - Dopamine Agents -- pharmacology KW - Receptors, Dopamine D2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67523833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dopamine+D3+receptor+ligands+block+nicotine-induced+conditioned+place+preferences+through+a+mechanism+that+does+not+involve+discriminative-stimulus+or+antidepressant-like+effects.&rft.au=Le+Foll%2C+Bernard%3BSokoloff%2C+Pierre%3BStark%2C+Holger%3BGoldberg%2C+Steven+R&rft.aulast=Le+Foll&rft.aufirst=Bernard&rft.date=2005-04-01&rft.volume=30&rft.issue=4&rft.spage=720&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 - 2005-07-28 N1 - Date created - 2005-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular profiles of mRNA levels in laser capture microdissected murine hippocampal regions differentially responsive to TMT-induced cell death. AN - 67523816; 15773920 AB - Using a chemical-induced model of dentate granule (DG) cell death, cDNA microarray analysis was used to identify gene profiles from the laser-captured microdissected (LCM) hippocampal DG cell region versus the CA pyramidal cell layer (CA) from 21-day-old male CD1 mice injected with trimethyltin hydroxide (TMT; 3.0 mg/kg, i.p.). At 6 h post-TMT, lectin + microglia displaying a reactive morphology were in contact with active caspase 3+ neurons. By 18 h, amoeboid microglia and signs of phagocytosis, and a mild astrocytic response were present in the DG. There was no evidence of IgG extravasation in the hippocampus, or cell death and glial reactivity in the CA. Atlas 1.2K Clontech array detected 115 genes changed in the hippocampus with TMT and included genes associated with immediate-early responses, calcium homeostasis, cellular signaling, cell cycle, immunomodulation and DNA repair. Early responses localized to LCM DG samples consisted of elevations in inflammatory factors such as tumor necrosis factor-alpha and receptors, as well as MIP1alpha, CD14, CD18, and a decrease in factors associated with calcium buffering. By 18 h, in the DG, changes occurred in transcripts associated with apoptosis, cell adhesion, DNA repair, cell proliferation and growth. In the CA, a differential level of elevation was seen in CD86 antigen, zinc finger protein 38 and DNA damage inducible transcript 3. A significant number of genes was decreased at these early time points in both hippocampal regions. JF - Journal of neurochemistry AU - Lefebvre d'Hellencourt, Christian AU - Harry, G Jean AD - Neurotoxicology Group, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Health and Human Services, Research Triangle Park, North Carolina 27709, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 206 EP - 220 VL - 93 IS - 1 SN - 0022-3042, 0022-3042 KW - Glial Fibrillary Acidic Protein KW - 0 KW - Lectins KW - RNA, Messenger KW - Trimethyltin Compounds KW - trimethyltin hydroxide KW - 56-24-6 KW - Casp3 protein, mouse KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Phosphopyruvate Hydratase KW - EC 4.2.1.11 KW - Index Medicus KW - Animals KW - Microdissection -- methods KW - Glial Fibrillary Acidic Protein -- metabolism KW - Disease Models, Animal KW - Mice KW - Immunohistochemistry -- methods KW - Reverse Transcriptase Polymerase Chain Reaction -- methods KW - Cell Death -- drug effects KW - Caspases -- metabolism KW - Glial Fibrillary Acidic Protein -- genetics KW - Phosphopyruvate Hydratase -- metabolism KW - Cell Count -- methods KW - Microarray Analysis -- methods KW - Lasers KW - Gene Expression Regulation -- drug effects KW - Time Factors KW - Astrocytes -- pathology KW - Male KW - Lectins -- metabolism KW - Astrocytes -- metabolism KW - Neurons -- metabolism KW - Brain Injuries -- genetics KW - RNA, Messenger -- metabolism KW - Hippocampus -- metabolism KW - Hippocampus -- pathology KW - Brain Injuries -- chemically induced KW - Neurons -- pathology KW - Brain Injuries -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67523816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+profiles+of+mRNA+levels+in+laser+capture+microdissected+murine+hippocampal+regions+differentially+responsive+to+TMT-induced+cell+death.&rft.au=Lefebvre+d%27Hellencourt%2C+Christian%3BHarry%2C+G+Jean&rft.aulast=Lefebvre+d%27Hellencourt&rft.aufirst=Christian&rft.date=2005-04-01&rft.volume=93&rft.issue=1&rft.spage=206&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 - 2005-05-16 N1 - Date created - 2005-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - On criteria for evaluating models of absolute risk. AN - 67521658; 15772102 AB - Absolute risk is the probability that an individual who is free of a given disease at an initial age, a, will develop that disease in the subsequent interval (a, t]. Absolute risk is reduced by mortality from competing risks. Models of absolute risk that depend on covariates have been used to design intervention studies, to counsel patients regarding their risks of disease and to inform clinical decisions, such as whether or not to take tamoxifen to prevent breast cancer. Several general criteria have been used to evaluate models of absolute risk, including how well the model predicts the observed numbers of events in subsets of the population ("calibration"), and "discriminatory power," measured by the concordance statistic. In this paper we review some general criteria and develop specific loss function-based criteria for two applications, namely whether or not to screen a population to select subjects for further evaluation or treatment and whether or not to use a preventive intervention that has both beneficial and adverse effects. We find that high discriminatory power is much more crucial in the screening application than in the preventive intervention application. These examples indicate that the usefulness of a general criterion such as concordance depends on the application, and that using specific loss functions can lead to more appropriate assessments. JF - Biostatistics (Oxford, England) AU - Gail, Mitchell H AU - Pfeiffer, Ruth M AD - Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Executive Plaza South, EPS 8032, Bethesda, MD 20892-7244, USA. gailm@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 227 EP - 239 VL - 6 IS - 2 SN - 1465-4644, 1465-4644 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Tamoxifen -- therapeutic use KW - Humans KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Tamoxifen -- adverse effects KW - Breast Neoplasms -- prevention & control KW - Middle Aged KW - Colonoscopy -- standards KW - Colonic Neoplasms -- diagnosis KW - Female KW - Risk KW - Models, Statistical KW - Decision Making KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67521658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+review+of+anticancer+therapy&rft.atitle=Clodronate+in+the+prevention+and+treatment+of+skeletal+metastasis.&rft.au=Gulley%2C+James%3BDahut%2C+William+L&rft.aulast=Gulley&rft.aufirst=James&rft.date=2005-04-01&rft.volume=5&rft.issue=2&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Expert+review+of+anticancer+therapy&rft.issn=1744-8328&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-21 N1 - Date created - 2005-03-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Biostatistics. 2005 Jul;6(3):500-2; author reply 503-4 [15917375] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitrogen mineralization potentials in three tropical soils treated with biosolids. AN - 67513179; 15763098 AB - This study attained anaerobic biosolids (DS) and aerobic biosolids (MS) from the wastewater treatment plants in Kaohsiung and Taipei, Taiwan. Three tropical soils (Lt, Cp and Ca) were selected for incubation with the two biosolids at application rates of 10, 50 and 100 Mg ha(-1) for 48 weeks. This study aims to characterize the influence of the application of biosolids on the soil potential for N mineralization (N0) and also to elucidate the kinetics of N mineralization in tropical soils treated with different biosolids. Experimental results indicate that the amounts of N mineralized accumulated in the biosolids-treated soils during the incubation period tended to match the first-order kinetics calculated by the nonlinear least squares equation. The N0 values of the MS biosolids-treated soils greatly exceeded those of the DS soils. The rates of N mineralization (k) of the DS biosolids-treated soils varied greatly from 0.047 to 0.075 week(-1) and that of the MS soils varied from 0.047 to 0.105 week(-1). Little of the organic N fraction in the biosolids remained available for further mineralization following 48 weeks of incubation. Based on the demand of N uptake by vegetables grown in Taiwanese soils, the rates of biosolids application to the soils are safe, as determined by the amount of N mineralization that does not cause nitrate accumulation. JF - Chemosphere AU - Hseu, Zeng-Yei AU - Huang, Cheng-Chieh AD - Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, 1, Hseih-Fu Rd., Nei-Pu, Pingtung 91201, Taiwan, ROC. zyhseu@mail.npust.edu.tw Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 447 EP - 454 VL - 59 IS - 3 SN - 0045-6535, 0045-6535 KW - Sewage KW - 0 KW - Soil KW - Nitrogen KW - N762921K75 KW - Index Medicus KW - Taiwan KW - Analysis of Variance KW - Kinetics KW - Hydrogen-Ion Concentration KW - Least-Squares Analysis KW - Tropical Climate KW - Nitrogen -- chemistry KW - Soil -- analysis KW - Sewage -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67513179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemosphere&rft.atitle=Nitrogen+mineralization+potentials+in+three+tropical+soils+treated+with+biosolids.&rft.au=Hseu%2C+Zeng-Yei%3BHuang%2C+Cheng-Chieh&rft.aulast=Hseu&rft.aufirst=Zeng-Yei&rft.date=2005-04-01&rft.volume=59&rft.issue=3&rft.spage=447&rft.isbn=&rft.btitle=&rft.title=Chemosphere&rft.issn=00456535&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-09 N1 - Date created - 2005-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Salivary hypofunction and xerostomia: diagnosis and treatment. AN - 67494214; 15755407 AB - Salivary gland hypofunction and complaints of xerostomia are common in elderly patients, irrespective of their living situation. Medication use is frequently related to dry mouth symptoms and reductions in salivary flow rates. Patients with reduced salivary flow are at increased risk for caries, oral fungal infections, swallowing problems, and diminished or altered taste. Oral health care providers should institute aggressive preventive measures and recommend palliative care for patients with significant reduction in salivary gland function. The systemic agents pilocarpine and cevimeline may help selected patients. Selective use of fluoride-releasing restorative materials and conservative treatment plans are recommended for this patient group. JF - Dental clinics of North America AU - Atkinson, Jane C AU - Grisius, Margaret AU - Massey, Ward AD - Comprehensive Care and Therapeutics, University of Maryland Dental School, 666 West Baltimore Street, 3E-32, Baltimore, MD 21201-1586, USA. jatkinso@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 309 EP - 326 VL - 49 IS - 2 SN - 0011-8532, 0011-8532 KW - Cariostatic Agents KW - 0 KW - Quinuclidines KW - Thiophenes KW - Pilocarpine KW - 01MI4Q9DI3 KW - cevimeline KW - K9V0CDQ56E KW - Fluorides KW - Q80VPU408O KW - Dentistry KW - Index Medicus KW - Thiophenes -- therapeutic use KW - Pilocarpine -- therapeutic use KW - Aged, 80 and over KW - Salivation -- drug effects KW - Humans KW - Polypharmacy KW - Cariostatic Agents -- therapeutic use KW - Quinuclidines -- therapeutic use KW - Aged KW - Sjogren's Syndrome -- complications KW - Radiotherapy -- adverse effects KW - Fluorides -- therapeutic use KW - Xerostomia -- etiology KW - Xerostomia -- prevention & control KW - Xerostomia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67494214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Dental+clinics+of+North+America&rft.atitle=Salivary+hypofunction+and+xerostomia%3A+diagnosis+and+treatment.&rft.au=Atkinson%2C+Jane+C%3BGrisius%2C+Margaret%3BMassey%2C+Ward&rft.aulast=Atkinson&rft.aufirst=Jane&rft.date=2005-04-01&rft.volume=49&rft.issue=2&rft.spage=309&rft.isbn=&rft.btitle=&rft.title=Dental+clinics+of+North+America&rft.issn=00118532&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-28 N1 - Date created - 2005-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MC1R and the response of melanocytes to ultraviolet radiation. AN - 67491936; 15748644 AB - The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists alpha-melanocyte-stimulating hormone (alphaMSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of alphaMSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is considered a melanoma susceptibility gene, and its significance in determining the risk for skin cancer is of tremendous interest. JF - Mutation research AU - Rouzaud, Francois AU - Kadekaro, Ana Luisa AU - Abdel-Malek, Zalfa A AU - Hearing, Vincent J AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892, USA. Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 133 EP - 152 VL - 571 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Melanins KW - 0 KW - Receptor, Melanocortin, Type 1 KW - Index Medicus KW - Alleles KW - Melanins -- physiology KW - Humans KW - Ultraviolet Rays KW - Receptor, Melanocortin, Type 1 -- physiology KW - Receptor, Melanocortin, Type 1 -- genetics KW - Receptor, Melanocortin, Type 1 -- agonists KW - Melanocytes -- radiation effects KW - Receptor, Melanocortin, Type 1 -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67491936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=MC1R+and+the+response+of+melanocytes+to+ultraviolet+radiation.&rft.au=Rouzaud%2C+Francois%3BKadekaro%2C+Ana+Luisa%3BAbdel-Malek%2C+Zalfa+A%3BHearing%2C+Vincent+J&rft.aulast=Rouzaud&rft.aufirst=Francois&rft.date=2005-04-01&rft.volume=571&rft.issue=1-2&rft.spage=133&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 - 2005-05-12 N1 - Date created - 2005-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of the myoglobin tyrosyl radical by immuno-spin trapping and its dimerization. AN - 67488808; 15749393 AB - 5,5-Dimethyl-1-pyrroline N-oxide (DMPO) spin trapping in conjunction with antibodies specific for the DMPO nitrone epitope was used on hydrogen peroxide-treated sperm whale and horse heart myoglobins to determine the site of protein nitrone adduct formation. The present study demonstrates that the sperm whale myoglobin tyrosyl radical, formed by hydrogen peroxide-dependent self-peroxidation, can either react with another tyrosyl radical, resulting in a dityrosine cross-linkage, or react with the spin trap DMPO to form a diamagnetic nitrone adduct. The reaction of sperm whale myoglobin with equimolar hydrogen peroxide resulted in the formation of a myoglobin dimer detectable by electrophoresis/protein staining. Addition of DMPO resulted in the trapping of the globin radical, which was detected by Western blot. The location of this adduct was demonstrated to be at tyrosine-103 by MS/MS and site-specific mutagenicity. Interestingly, formation of the myoglobin dimer, which is known to be formed primarily by cross-linkage of tyrosine-151, was inhibited by the addition of DMPO. JF - Free radical biology & medicine AU - Detweiler, Charles D AU - Lardinois, Olivier M AU - Deterding, Leesa J AU - de Montellano, Paul R Ortiz AU - Tomer, Kenneth B AU - Mason, Ronald P AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, MD F0-01, Research Triangle Park, NC 27709, USA. Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 969 EP - 976 VL - 38 IS - 7 SN - 0891-5849, 0891-5849 KW - Antibodies KW - 0 KW - Cyclic N-Oxides KW - Epitopes KW - Free Radicals KW - Myoglobin KW - Nitrogen Oxides KW - Spin Labels KW - nitrones KW - Tyrosine KW - 42HK56048U KW - 5,5-dimethyl-1-pyrroline-1-oxide KW - 7170JZ1QF3 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Free Radicals -- analysis KW - Animals KW - Antibodies -- immunology KW - Dimerization KW - Hydrogen Peroxide -- pharmacology KW - Amino Acid Sequence KW - Mutagenesis, Site-Directed KW - Cyclic N-Oxides -- analysis KW - Nitrogen Oxides -- immunology KW - Molecular Sequence Data KW - Cyclic N-Oxides -- chemistry KW - Epitopes -- immunology KW - Whales KW - Antibodies -- chemistry KW - Spin Trapping KW - Myoglobin -- immunology KW - Myoglobin -- genetics KW - Myoglobin -- chemistry KW - Tyrosine -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67488808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+the+myoglobin+tyrosyl+radical+by+immuno-spin+trapping+and+its+dimerization.&rft.au=Detweiler%2C+Charles+D%3BLardinois%2C+Olivier+M%3BDeterding%2C+Leesa+J%3Bde+Montellano%2C+Paul+R+Ortiz%3BTomer%2C+Kenneth+B%3BMason%2C+Ronald+P&rft.aulast=Detweiler&rft.aufirst=Charles&rft.date=2005-04-01&rft.volume=38&rft.issue=7&rft.spage=969&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 - 2005-09-26 N1 - Date created - 2005-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytotoxicity of RH1: NAD(P)H:quinone acceptor oxidoreductase (NQO1)-independent oxidative stress and apoptosis induction. AN - 67486176; 15746574 AB - The elevated expression of the flavoprotein NAD(P)H:quinone acceptor oxidoreductase (NQO1) (EC 1.6.99.2) in many human solid tumors, along with its ability to activate quinone-based anticancer agents, makes it an excellent target for enzyme-directed drug development. Previous studies have shown a significant statistical correlation between NQO1 enzymatic activity and the cytotoxicity of certain antitumor quinones. RH1 [2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone], presently in late preclinical and entering early clinical development, has been previously considered to be an excellent substrate for activation by NQO1. In this study we investigate the cytotoxicity of RH1 in cell lines selected from the NCI's 60 tumor cell line panel, expressing varying levels of NQO1 activity. Exposure time- and concentration-dependent cytotoxicity was seen, apparently independent from levels of NQO1 activity in these cells. Furthermore, the NQO1 inhibitor dicoumarol had no impact on the sensitivity profiles of RH1 response. The HL-60 myeloid leukemia cells, which do not have detectable NQO1 activity, were further investigated. RH1 treatment of HL-60 cells generated high levels of free radicals, which was accompanied by robust redox cycling, oxygen consumption and induction of apoptosis. These results are in agreement with previous data suggesting that, in addition to its activation by NQO1, RH1-induced cytotoxicity might involve alternative pathways for activation of this compound. Furthermore, the high cytotoxicity of RH1 in the leukemia/lymphoma subpanel of the NCI in vitro cell line screen would suggest an empirical rationale for the utilization of this compound in the treatment of these malignancies. JF - Anti-cancer drugs AU - Tudor, Gabriela AU - Alley, Mike AU - Nelson, Christopher M AU - Huang, Ruili AU - Covell, David G AU - Gutierrez, Peter AU - Sausville, Edward A AD - Science Applications International Corp., National Cancer Institute, Frederick, MD, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 381 EP - 391 VL - 16 IS - 4 SN - 0959-4973, 0959-4973 KW - 2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone KW - 0 KW - Aziridines KW - Benzoquinones KW - Free Radicals KW - NAD(P)H Dehydrogenase (Quinone) KW - EC 1.6.5.2 KW - NQO1 protein, human KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Oxidation-Reduction KW - HL-60 Cells -- metabolism KW - HL-60 Cells -- drug effects KW - Transfection KW - Dose-Response Relationship, Drug KW - Oxygen -- metabolism KW - Humans KW - Time Factors KW - Free Radicals -- metabolism KW - Benzoquinones -- toxicity KW - Aziridines -- toxicity KW - Apoptosis -- drug effects KW - Oxidative Stress -- drug effects KW - NAD(P)H Dehydrogenase (Quinone) -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67486176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anti-cancer+drugs&rft.atitle=Cytotoxicity+of+RH1%3A+NAD%28P%29H%3Aquinone+acceptor+oxidoreductase+%28NQO1%29-independent+oxidative+stress+and+apoptosis+induction.&rft.au=Tudor%2C+Gabriela%3BAlley%2C+Mike%3BNelson%2C+Christopher+M%3BHuang%2C+Ruili%3BCovell%2C+David+G%3BGutierrez%2C+Peter%3BSausville%2C+Edward+A&rft.aulast=Tudor&rft.aufirst=Gabriela&rft.date=2005-04-01&rft.volume=16&rft.issue=4&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=Anti-cancer+drugs&rft.issn=09594973&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-05 N1 - Date created - 2005-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetics of individual differences in bitter taste perception: lessons from the PTC gene. AN - 67470059; 15733260 AB - The ability or inability to taste the compound phenylthiocarbamide (PTC) is a classic inherited trait in humans and has been the subject of genetic and anthropological studies for over 70 years. This trait has also been shown to correlate with a number of dietary preferences and thus may have important implications for human health. The recent identification of the gene that underlies this phenotype has produced several surprising findings. This gene is a member of the T2R family of bitter taste receptor genes. It exists in seven different allelic forms, although only two of these, designated the major taster and major non-taster forms, exist at high frequency outside sub-Saharan Africa. The non-taster allele resides on a small chromosomal region identical by descent, indicating that non-tasters are descended from an ancient founder individual, and consistent with an origin of the non-taster allele preceding the emergence of modern humans out of Africa. The two major forms differ from each other at three amino acid positions, and both alleles have been maintained at high frequency by balancing natural selection, suggesting that the non-taster allele serves some function. We hypothesize that this function is to serve as a receptor for another, as yet unidentified toxic bitter substance. At least some of the remaining five haplotypes appear to confer intermediate sensitivity to PTC, suggesting future detailed studies of the relationships between receptor structure and taste function. JF - Clinical genetics AU - Kim, U K AU - Drayna, D AD - National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 275 EP - 280 VL - 67 IS - 4 SN - 0009-9163, 0009-9163 KW - Receptors, Cell Surface KW - 0 KW - Receptors, G-Protein-Coupled KW - taste receptors, type 2 KW - Phenylthiourea KW - 6F82C6Q54C KW - Index Medicus KW - Phenotype KW - Genotype KW - Genetic Linkage KW - Alleles KW - Haplotypes KW - Genetics, Population KW - African Continental Ancestry Group -- genetics KW - Humans KW - Founder Effect KW - Evolution, Molecular KW - Taste -- genetics KW - Receptors, Cell Surface -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67470059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+genetics&rft.atitle=Genetics+of+individual+differences+in+bitter+taste+perception%3A+lessons+from+the+PTC+gene.&rft.au=Kim%2C+U+K%3BDrayna%2C+D&rft.aulast=Kim&rft.aufirst=U&rft.date=2005-04-01&rft.volume=67&rft.issue=4&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Clinical+genetics&rft.issn=00099163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-16 N1 - Date created - 2005-02-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Clin Genet. 2005 Jun;67(6):534 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tissue homeostasis and the control of the neoplastic phenotype in epithelial cancers. AN - 67370199; 15652452 AB - Neoplastic cells at various stages of tumor progression may remain dormant for many years. The suppression of the neoplastic phenotype and tumor outgrowth depends on close contact of neoplastic cells with surrounding normal cells. This review examines the nature of these contacts primarily in models for skin cancer induction. Junctional complexes, membrane associated growth factors and their receptors, and paracrine mechanisms likely contribute to this state of tumor cell dormancy. Understanding these mechanisms will be important in primary cancer prevention and for counteracting recurrences in cancer survivors. JF - Seminars in cancer biology AU - Glick, Adam B AU - Yuspa, Stuart H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, 37 Convent Drive, MSC-4255, Building 37, Room 4068A1, Bethesda, MD 20892-4255, USA. Y1 - 2005/04// PY - 2005 DA - April 2005 SP - 75 EP - 83 VL - 15 IS - 2 SN - 1044-579X, 1044-579X KW - Index Medicus KW - Phenotype KW - Animals KW - Gap Junctions -- physiology KW - Cell Communication KW - Homeostasis KW - Carcinoma -- etiology KW - Carcinoma -- pathology KW - Skin Neoplasms -- etiology KW - Skin Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67370199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+cancer+biology&rft.atitle=Tissue+homeostasis+and+the+control+of+the+neoplastic+phenotype+in+epithelial+cancers.&rft.au=Glick%2C+Adam+B%3BYuspa%2C+Stuart+H&rft.aulast=Glick&rft.aufirst=Adam&rft.date=2005-04-01&rft.volume=15&rft.issue=2&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Seminars+in+cancer+biology&rft.issn=1044579X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-14 N1 - Date created - 2005-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonparametric Adjustment Techniques for Binary Covariates AN - 21095186; 11132754 AB - Though a variety of reasons are often articulated for adjusting analyses for covariates, these reasons often fall into one of two general objectives, specifically to increase precision or to decrease bias. In practice, one does not generally choose between these objectives, because the methods that address one tend to address the other, as well. Because of this, no distinction is made in the methods used to correct for a baseline imbalance with respect to a prognostic covariate versus to ensure a fair comparison across treatment groups by making the comparisons within the levels of a prognostic covariate. Yet the literal translation of these two uses of covariate adjustment will lead to two distinct adjustment methods. We illustrate this divergence in the simplest case of a single binary covariate, a binary outcome, and two treatments, and we note that it is possible to combine the two approaches to derive yet a third approach. Each of these approaches is nonparametric and exact, and so it is the precise reason for adjusting that should dictate which would be used in any given situation. JF - Biometrical Journal AU - Berger, Vance W AD - National Cancer Institute and University of Maryland Baltimore County, EPN 3131, 6130 Executive Boulevard, MSC-7354, Bethesda, MD 20892-7354, USA, vb78c@nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 199 EP - 205 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 47 IS - 2 SN - 0323-3847, 0323-3847 KW - Biotechnology and Bioengineering Abstracts KW - Translation KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21095186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nonparametric+Adjustment+Techniques+for+Binary+Covariates&rft.au=Berger%2C+Vance+W&rft.aulast=Berger&rft.aufirst=Vance&rft.date=2005-04-01&rft.volume=47&rft.issue=2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200410100 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Translation DO - http://dx.doi.org/10.1002/bimj.200410100 ER - TY - JOUR T1 - Quantifying the Magnitude of Baseline Covariate Imbalances Resulting from Selection Bias in Randomized Clinical Trials AN - 21091582; 11132743 AB - Selection bias is most common in observational studies, when patients select their own treatments or treatments are assigned based on patient characteristics, such as disease severity. This first-order selection bias, as we call it, is eliminated by randomization, but there is residual selection bias that may occur even in randomized trials which occurs when, subconsciously or otherwise, an investigator uses advance knowledge of upcoming treatment allocations as the basis for deciding whom to enroll. For example, patients more likely to respond may be preferentially enrolled when the active treatment is due to be allocated, and patients less likely to respond may be enrolled when the control group is due to be allocated. If the upcoming allocations can be observed in their entirety, then we will call the resulting selection bias second-order selection bias. Allocation concealment minimizes the ability to observe upcoming allocations, yet upcoming allocations may still be predicted (imperfectly), or even determined with certainty, if at least some of the previous allocations are known, and if restrictions (such as randomized blocks) were placed on the randomization. This mechanism, based on prediction but not observation of upcoming allocations, is the third-order selection bias that is controlled by perfectly successful masking, but without perfect masking is not controlled even by the combination of advance randomization and allocation concealment. Our purpose is to quantify the magnitude of baseline imbalance that can result from third-order selection bias when the randomized block procedure is used. The smaller the block sizes, the more accurately one can predict future treatment assignments in the same block as known previous assignments, so this magnitude will depend on the block size, as well as on the level of certainty about upcoming allocations required to bias the patient selection. We find that a binary covariate can, on average, be up to 50% unbalanced by third-order selection bias. JF - Biometrical Journal AU - Berger, Vance W AD - National Cancer Institute, University of Maryland Baltimore County, Biometry Research Group, National Cancer Institute, Executive Plaza North, Suite 3131, 6130 Executive Boulevard, MSC 7354, Bethesda, MD 20892-7354, USA, vb78c@nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 119 EP - 127 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 47 IS - 2 SN - 0323-3847, 0323-3847 KW - Biotechnology and Bioengineering Abstracts KW - Clinical trials KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21091582?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Quantifying+the+Magnitude+of+Baseline+Covariate+Imbalances+Resulting+from+Selection+Bias+in+Randomized+Clinical+Trials&rft.au=Berger%2C+Vance+W&rft.aulast=Berger&rft.aufirst=Vance&rft.date=2005-04-01&rft.volume=47&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200410106 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Clinical trials DO - http://dx.doi.org/10.1002/bimj.200410106 ER - TY - JOUR T1 - Power and Sample Size Calculation of Comparative Diagnostic Accuracy Studies with Multiple Correlated Test Results AN - 21075080; 11132748 AB - We consider the power and sample size calculation of diagnostic studies with normally distributed multiple correlated test results. We derive test statistics and obtain power and sample size formulas. The methods are illustrated using an example of comparison of CT and PET scanner for detecting extra-hepatic disease for colorectal cancer. JF - Biometrical Journal AU - Liu, Aiyi AU - Schisterman, Enrique F AU - Mazumdar, Madhu AU - Hu, Jiang AD - Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, Department of Health and Human Services, 6100 Executive Blvd., Rockville, MD 20852, USA, liua@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 140 EP - 150 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 47 IS - 2 SN - 0323-3847, 0323-3847 KW - Biotechnology and Bioengineering Abstracts KW - Statistics KW - Colorectal cancer KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21075080?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Power+and+Sample+Size+Calculation+of+Comparative+Diagnostic+Accuracy+Studies+with+Multiple+Correlated+Test+Results&rft.au=Liu%2C+Aiyi%3BSchisterman%2C+Enrique+F%3BMazumdar%2C+Madhu%3BHu%2C+Jiang&rft.aulast=Liu&rft.aufirst=Aiyi&rft.date=2005-04-01&rft.volume=47&rft.issue=2&rft.spage=140&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200410094 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Colorectal cancer; Statistics DO - http://dx.doi.org/10.1002/bimj.200410094 ER - TY - JOUR T1 - Differential Expression of Cytokines and Chemokines in Human Monocytes Induced by Lipid Formulations of Amphotericin B AN - 20714068; 6243586 AB - The immunomodulatory effects of liposomal amphotericin B (LAMB), amphotericin B lipid complex (ABLC), and amphotericin B colloidal dispersion (ABCD) on mRNA and protein profiles of five cytokines and chemokines expressed by human monocyte-enriched mononuclear leukocytes (MNCs) were comprehensively evaluated by semiquantitative reverse transcription-PCR and enzyme-linked immunosorbent assays; they were compared to those of deoxycholate amphotericin B (DAMB). mRNAs of interleukin-1 beta (IL-1 beta ), IL-1 receptor antagonist (IL-1ra), tumor necrosis factor alpha (TNF- alpha ), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1 beta (MIP-1 beta ) were assessed after treatment of MNCs with each drug for 0.5, 2, 6, and 22 h. The cytokine protein profiles were obtained after incubation of MNCs with the drugs for 2 h (TNF- alpha ) or 6 h (all the others). In the mRNA studies, DAMB resulted in an early increase of inflammatory cytokines or chemokines IL-1 beta , TNF- alpha , MCP-1, and MIP-1 beta (2 to 6 h) and in a late increase of anti-inflammatory IL-1ra (22 h). ABCD showed a general similar trend of inflammatory gene up-regulation. LAMB and ABLC decreased or did not affect IL-1 beta and TNF- alpha , whereas ABLC additionally decreased MIP-1 beta . In protein measurement studies, DAMB and ABCD up-regulated production of IL-1 beta (P < 0.05), decreased the IL-1ra/IL-1 beta ratio, and up-regulated the production of MCP-1 and MIP-1 beta . In comparison, LAMB and ABLC down-regulated or did not affect the production of these cytokines/chemokines compared to untreated MNCs; furthermore, ABLC tended to increase the IL-1ra/IL-1 beta ratio. These studies demonstrate that amphotericin B formulations differentially affect gene expression and release of an array of proinflammatory and anti-inflammatory cytokines that potentially may explain the differences in infusion-related reactions and dose-dependent nephrotoxicity as well as modulation of the host immune response to invasive fungal infections. JF - Antimicrobial Agents & Chemotherapy AU - Simitsopoulou, M AU - Roilides, E AU - Dotis, J AU - Dalakiouridou, M AU - Dudkova, F AU - Andreadou, E AU - Walsh, T J AD - Laboratory of Infectious Diseases, 3rd Department of Pediatrics, School of Medicine, Aristotle University of Thessaloniki. Laboratory of Medical Biotechnology, Department of Medical Laboratories, Technological Educational Institute, Thessaloniki, Greece. Immunocompromised Host Section, National Cancer Institute, Bethesda, Maryland Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 1397 EP - 1403 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 49 IS - 4 SN - 0066-4804, 0066-4804 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts A: Industrial & Applied Microbiology; Immunology Abstracts KW - Leukocytes (mononuclear) KW - Amphotericin B KW - Chemokines KW - Enzyme-linked immunosorbent assay KW - Monocyte chemoattractant protein 1 KW - Lipids KW - Interleukin 1 KW - Transcription KW - Infection KW - Immunomodulation KW - Interleukin 1 receptor antagonist KW - Inflammation KW - Antimicrobial agents KW - Gene expression KW - Cytokines KW - Immune response KW - Monocytes KW - Tumor necrosis factor- alpha KW - Macrophage inflammatory protein KW - Drugs KW - A 01340:Antibiotics & Antimicrobials KW - F 06955:Immunomodulation & Immunopharmacology KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20714068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transfer+of+a+TCR+Gene+Derived+from+a+Patient+with+a+Marked+Antitumor+Response+Conveys+Highly+Active+T-Cell+Effector+Functions&rft.au=Hughes%3BYu%2C+YYL%3BDudley%2C+ME%3BZheng%2C+Z%3BRobbins%2C+P+F%3BLi%2C+Y%3BWunderlich%2C+J%3BHawley%2C+R+G%3BMoayeri%2C+M%3BRosenberg%2C+SA%3BMorgan%2C+R+A&rft.aulast=Hughes&rft.aufirst=&rft.date=2005-04-01&rft.volume=16&rft.issue=4&rft.spage=457&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 - 2008-08-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Amphotericin B; Leukocytes (mononuclear); Enzyme-linked immunosorbent assay; Chemokines; Monocyte chemoattractant protein 1; Lipids; Interleukin 1; Transcription; Infection; Immunomodulation; Interleukin 1 receptor antagonist; Antimicrobial agents; Inflammation; Gene expression; Cytokines; Tumor necrosis factor- alpha; Monocytes; Immune response; Macrophage inflammatory protein; Drugs ER - TY - JOUR T1 - Anticancer metal compounds in NCI's tumor-screening database: putative mode of action AN - 20237971; 6201941 AB - Clustering analysis of tumor cell cytotoxicity profiles for the National Cancer Institute (NCI)'s open compound repository has been used to catalog over 1100 metal or metalloid containing compounds with potential anticancer activity. The molecular features and corresponding reactivity of these compounds have been analyzed in terms of properties of their metals, their associated organic components (ligands) and their capacity to inhibit tumor cell growth. Cytotoxic responses are influenced by both the identity of the metal and the properties of its coordination ligand, with clear associations between structural similarities and cytotoxicity. Assignments of mechanisms of action (MOAs) for these compounds could be segregated into four broad response classes according to preference for binding to biological sulfhydryl groups, chelation, generation of reactive oxygen species (ROS), and production of lipophilic ions. Correlations between specific cytotoxic responses and differential gene expression profiles within the NCI's tumor cell panel serve as a validation for candidate biological targets and putative MOA classes. In addition, specific sensitivity toward subsets of metal containing agents has been found for certain tumor cell panels. Taken together, our results expand the knowledge base available for evaluating, designing and developing new metal-based anticancer drugs that may provide the basis for target-specific therapeutics. JF - Biochemical Pharmacology AU - Huang, R AU - Wallqvist, A AU - Covell, D G AD - National Cancer Institute at Frederick, Developmental Therapeutics Program, Screening Technologies Branch, Laboratory of Computational Technologies, Frederick, MD 21702, USA, covell@mail.ncifcrf.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 1009 EP - 1039 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 69 IS - 7 SN - 0006-2952, 0006-2952 KW - Biotechnology and Bioengineering Abstracts KW - Data mining KW - NCI tumor screen KW - Metal compounds KW - Mechanism of action KW - Drug discovery KW - Cancer KW - Ions KW - Metals KW - Catalogs KW - Chelation KW - Sulfhydryl groups KW - Antitumor agents KW - Tumor cells KW - Lipophilic KW - Gene expression KW - Databases KW - Cytotoxicity KW - Reactive oxygen species KW - Antitumor activity KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20237971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+Pharmacology&rft.atitle=Anticancer+metal+compounds+in+NCI%27s+tumor-screening+database%3A+putative+mode+of+action&rft.au=Huang%2C+R%3BWallqvist%2C+A%3BCovell%2C+D+G&rft.aulast=Huang&rft.aufirst=R&rft.date=2005-04-01&rft.volume=69&rft.issue=7&rft.spage=1009&rft.isbn=&rft.btitle=&rft.title=Biochemical+Pharmacology&rft.issn=00062952&rft_id=info:doi/10.1016%2Fj.bcp.2005.01.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-09-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Metals; Ions; Catalogs; Chelation; Sulfhydryl groups; Tumor cells; Antitumor agents; Lipophilic; Gene expression; Databases; Cytotoxicity; Reactive oxygen species; Antitumor activity DO - http://dx.doi.org/10.1016/j.bcp.2005.01.001 ER - TY - JOUR T1 - The Rate of Serious Bacterial Infections Among HIV-Infected Children With Immune Reconstitution Who Have Discontinued Opportunistic Infection Prophylaxis AN - 20193653; 6267834 AB - OBJECTIVE: Receipt of highly active antiretroviral therapy is associated with a decrease in the incidence of opportunistic infections (OIs) among HIV-infected adults. The goal of Pediatric AIDS Clinical Trials Group protocol 1008 was to evaluate prospectively the incidence of serious bacterial infections (SBIs) and other OIs after discontinuation of OI and/or Pneumocystis jiroveci pneumonia (PCP) prophylaxis among HIV-infected pediatric subjects who experienced immune reconstitution while receiving stable antiretroviral therapy. METHODS: HIV-infected children and adolescents, 2 to 21 years of age, who had received OI and/or PCP prophylaxis for greater than or equal to 6 months were enrolled if they had sustained responses (>16 weeks before study entry) to antiretroviral therapy, with CD4 super(+) cell percentages of greater than or equal to 20% for patients >6 years of age or greater than or equal to 25% for patients 2 to 6 years of age. Prophylaxis was discontinued at entry. To identify whether any correlation existed between functional immune reconstitution and protection from OIs, subjects were immunized with the hepatitis A virus vaccine. The association between the humoral immune response and the likelihood of developing an OI was evaluated. RESULTS: A total of 235 HIV-infected subjects from 43 participating sites had a median follow-up period of 132 weeks, yielding 547 person-years of observation. Twenty SBIs were observed among 19 subjects, resulting in an incidence rate of 3.66 SBIs per 100 person-years (95% confidence interval: 2.24-5.66 SBIs per 100 person-years). Sixteen of the events were presumed bacterial pneumonia, with 4 proven SBIs. One participant experienced 2 separate pneumonia episodes, of presumed bacterial cause. Ten subjects who developed SBIs had baseline CD4 super(+) cell counts of greater than or equal to 750 cells per mm super(3), and 15 had CD4 super(+) cell percentages of greater than or equal to 25% at the time of their SBIs. Two subjects died as a result of non-SBI-related causes. There were no statistically significant differences in changes over time in CD4 super(+) cell counts or CD4 super(+) cell percentages between subjects who experienced primary end points and those who did not. There was no evidence that baseline protease inhibitor use, gender, race/ethnicity, age, or CD4 super(+) cell count or percentage affected the time to development of a SBI. CONCLUSIONS: OI or PCP prophylaxis can be withdrawn safely for HIV-infected pediatric patients who experience CD4 super(+) cell recovery while receiving stable antiretroviral therapy. More studies are needed to assess the association between antibody responses to neoantigens and the development of SBIs. JF - Pediatrics AU - Nachman, Sharon AU - Gona, Philimon AU - Dankner, Wayne AU - Weinberg, Adrianna AU - Yogev, Ram AU - Gershon, Anne AU - Rathore, Mobeen AU - Read, Jennifer S AU - Huang, Sharon AU - Elgie, Carol AU - Hudgens, Kim AU - Hughes, Walter AD - Stony Brook University, State University of New York, Stony Brook, New York. Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts. Duke University Medical Center, Durham, North Carolina. University of Colorado Health Sciences Center, Denver, Colorado. Northwestern University, Chicago, Illinois. Columbia Presbyterian Medical Center, New York, New York. University of Florida Health Science Center, Jacksonville, FL. National Institute of Child Health and Human Development, Bethesda, Maryland. Frontier Science and Technology Research Foundation, Amherst, New York. Social and Scientific Systems, Silver Spring, Maryland. St Jude Children's Research Hospital, Memphis, Tennessee Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - e488 EP - e494 PB - American Academy of Pediatrics, 141 Northwest Point Blvd. Elk Grove Village IL 60007-1098 USA, [mailto:journals@aap.org], [URL:http://www.aap.org] VL - 115 IS - 4 SN - 0031-4005, 0031-4005 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Acquired immune deficiency syndrome KW - Age KW - Hepatitis A virus KW - Pneumocystis KW - Statistical analysis KW - Clinical trials KW - Immune reconstitution KW - CD4 antigen KW - Immune response (humoral) KW - Ethnic groups KW - Races KW - Bacteria KW - Pediatrics KW - Adolescence KW - Proteinase inhibitors KW - antiretroviral therapy KW - Children KW - Opportunist infection KW - Antibodies KW - Human immunodeficiency virus KW - highly active antiretroviral therapy KW - Prophylaxis KW - Vaccines KW - Pneumonia KW - A 01340:Antibiotics & Antimicrobials KW - V 22360:AIDS and HIV KW - F 06905:Vaccines KW - J 02350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20193653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=The+Rate+of+Serious+Bacterial+Infections+Among+HIV-Infected+Children+With+Immune+Reconstitution+Who+Have+Discontinued+Opportunistic+Infection+Prophylaxis&rft.au=Nachman%2C+Sharon%3BGona%2C+Philimon%3BDankner%2C+Wayne%3BWeinberg%2C+Adrianna%3BYogev%2C+Ram%3BGershon%2C+Anne%3BRathore%2C+Mobeen%3BRead%2C+Jennifer+S%3BHuang%2C+Sharon%3BElgie%2C+Carol%3BHudgens%2C+Kim%3BHughes%2C+Walter&rft.aulast=Nachman&rft.aufirst=Sharon&rft.date=2005-04-01&rft.volume=115&rft.issue=4&rft.spage=e488&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-08-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Age; Acquired immune deficiency syndrome; Pediatrics; Adolescence; antiretroviral therapy; Proteinase inhibitors; Statistical analysis; Children; Clinical trials; Opportunist infection; Immune reconstitution; Antibodies; CD4 antigen; highly active antiretroviral therapy; Prophylaxis; Vaccines; Immune response (humoral); Races; Ethnic groups; Pneumonia; Bacteria; Human immunodeficiency virus; Hepatitis A virus; Pneumocystis ER - TY - JOUR T1 - Bacterial Small RNA Regulators AN - 19779564; 7373930 AB - Small regulatory RNAs can modify the activity of proteins and the stability and translation of mRNAs. They have now been found in a wide range of organisms, and can play previously unsuspected critical regulatory roles. The bacterial small RNAs include two major classes. The largest family (with at least 20 members in Escherichia coli K12) acts by basepairing with target mRNAs to modify mRNA translation or stability; this class of RNAs also uses an RNA chaperone protein, Hfq. DsrA is the best-studied example of this family of RNAs. It has been shown to positively regulate translation of the transcription factor RpoS by opening an inhibitory hairpin in the mRNA, and to negatively regulate translation of hns by pairing just beyond the translation initiation codon. The class of RNAs that modify activity of proteins is exemplified by CsrB and CsrC of E. coli, two RNAs that bind to and inhibit CsrA, a protein translational regulator. Homologs of CsrA and related regulatory RNAs have been implicated in the regulation of gluconeogenesis, biofilm formation, and virulence factor expression in plant and human pathogens. JF - Critical Reviews in Biochemistry and Molecular Biology AU - Majdalani, N AU - Vanderpool, C K AU - Gottesman, S AD - Bldg. 37, Rm. 5132, National Cancer Institute, Bethesda, MD 20892, USA, susang@helix.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 93 EP - 113 VL - 40 IS - 2 SN - 1040-9238, 1040-9238 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Translation KW - mRNA stability KW - virulence factors KW - Translation initiation KW - Transcription factors KW - Gluconeogenesis KW - Escherichia coli KW - Codons KW - Chaperones KW - Pathogens KW - Biofilms KW - A 01360:Plant Diseases KW - J 02320:Cell Biology KW - N 14830:RNA UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19779564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Critical+Reviews+in+Biochemistry+and+Molecular+Biology&rft.atitle=Bacterial+Small+RNA+Regulators&rft.au=Majdalani%2C+N%3BVanderpool%2C+C+K%3BGottesman%2C+S&rft.aulast=Majdalani&rft.aufirst=N&rft.date=2005-04-01&rft.volume=40&rft.issue=2&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Critical+Reviews+in+Biochemistry+and+Molecular+Biology&rft.issn=10409238&rft_id=info:doi/10.1080%2F10409230590918702 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-05-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Translation; mRNA stability; virulence factors; Translation initiation; Transcription factors; Gluconeogenesis; Codons; Chaperones; Biofilms; Pathogens; Escherichia coli DO - http://dx.doi.org/10.1080/10409230590918702 ER - TY - JOUR T1 - Data and Safety Monitoring in Clinical Research: A National Institute of Neurologic Disorders and Stroke Perspective AN - 19520350; 7231945 AB - The National Institute of Neurologic Disorders and Stroke supports a broad spectrum of research in the diagnosis and treatment of neurologic disease. Emergency medicine is increasingly involved in clinical research for patients with neurologic emergencies. Independent data and safety monitoring are critical components of clinical trials to ensure the protection of patients and the scientific integrity of the research. We review National Institute of Neurologic Disorders and Stroke principles of data and safety monitoring and provide examples to illustrate key concepts. JF - Annals of Emergency Medicine AU - Conwit, R A AU - Hart, R G AU - Moy, C S AU - Marler, J R AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Neuroscience Center, Bethesda, MD, USA Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 388 EP - 392 VL - 45 IS - 4 SN - 0196-0644, 0196-0644 KW - neurological disorders KW - Health & Safety Science Abstracts KW - Reviews KW - clinical trials KW - Research programs KW - H 13000:Medical Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19520350?accountid=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=Annals+of+Emergency+Medicine&rft.atitle=Data+and+Safety+Monitoring+in+Clinical+Research%3A+A+National+Institute+of+Neurologic+Disorders+and+Stroke+Perspective&rft.au=Conwit%2C+R+A%3BHart%2C+R+G%3BMoy%2C+C+S%3BMarler%2C+J+R&rft.aulast=Conwit&rft.aufirst=R&rft.date=2005-04-01&rft.volume=45&rft.issue=4&rft.spage=388&rft.isbn=&rft.btitle=&rft.title=Annals+of+Emergency+Medicine&rft.issn=01960644&rft_id=info:doi/10.1016%2Fj.annemergmed.2004.08.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-02-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Reviews; clinical trials; Research programs DO - http://dx.doi.org/10.1016/j.annemergmed.2004.08.006 ER - TY - JOUR T1 - The prevalence and clinical significance of amniotic fluid 'sludge' in patients with preterm labor and intact membranes AN - 19432416; 6786691 AB - Objective: To determine the prevalence and clinical significance of amniotic fluid (AF) 'sludge' observed during transvaginal ultrasound examination of the cervix in patients with preterm labor and intact membranes, and in those with uncomplicated pregnancies. Methods: This retrospective study included patients with preterm labor and intact membranes (n = 84) and those with uncomplicated term pregnancies (n = 298). The outcome variables included the occurrence of documented microbial invasion of the amniotic cavity (MIAC), histological chorioamnionitis, examination-to-delivery interval, admission to the neonatal intensive care unit (NICU), a composite neonatal morbidity, perinatal death, and delivery within 48 h, 7 days, and < 35 weeks and < 32 weeks. Statistical analysis included Chi-square test, stepwise logistic regression analysis and survival analysis. Results: The prevalence of AF 'sludge' was 1% (3/298) in patients with uncomplicated term pregnancies and 22.6% (19/84) in those with preterm labor and intact membranes. Among patients with preterm labor and intact membranes: (1) cervical length less than or equal to 15 mm was present in 58.3% (49/84) of the patients; (2) the prevalence of MIAC and histological chorioamnionitis was 12.1% (7/58) and 32.9% (25/76), respectively; (3) the rate of spontaneous preterm delivery within 48 h, 7 days, and < 32 weeks and < 35 weeks of gestation was 13.6% (8/59), 28.8% (17/59), 39.5% (17/43) and 50.8% (30/59), respectively; (4) patients with AF 'sludge' had a higher frequency of positive AF cultures [33.3% (6/18) vs. 2.5% (1/40), P = 0.003] and histological chorioamnionitis [77.8% (14/18) vs. 19% (11/58), P < 0.001] than those without AF 'sludge'; (5) a higher proportion of neonates born to patients with AF 'sludge' was admitted to the NICU [64.3% (9/14) vs. 12.9% (8/62), P < 0.01], had a composite neonatal morbidity [36.8% (7/19) vs. 13.8% (9/65), P = 0.04] and died in the perinatal period [36.8% (7/19) vs. 4.6% (3/65), P = 0.001] than those born to women without 'sludge'; (6) a higher proportion of patients with AF 'sludge' had spontaneous delivery within 48 h [42.9% (6/14) vs. 4.4% (2/45), P = 0.001], within 7 days [71.4% (10/14) vs. 15.6% (7/45), P < 0.001], < 32 weeks [75% (9/12) vs. 25.8% (8/31), P = 0.005] and < 35 weeks [92.9% (13/14) vs. 37.8% (17/45), P < 0.001] than those without AF 'sludge'; and (7) patients with AF 'sludge' had a shorter examination-to-delivery interval than those without AF 'sludge' [AF 'sludge' median, 1 (IQR, 1-5) days vs. no AF 'sludge' median, 33 (IQR, 18-58) days; P < 0.001]. Conclusion: The presence of AF 'sludge' in patients with preterm labor and intact membranes is a risk factor for MIAC, histological chorioamnionitis and impending preterm delivery. JF - Ultrasound in Obstetrics and Gynecology AU - Espinoza, J AU - Goncalves, L F AU - Romero, R AU - Nien, J K AU - Stites, S AU - Kim, Y M AU - Hassan, S AU - Gomez, R AU - Yoon, B H AU - Chaiworapongsa, T AU - Lee, W AU - Mazor, M AD - Perinatology Research Branch, NICHD/NIH/DHHS, 4707 St Antoine Boulevard, Detroit, MI 48201, USA, warfiela@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 346 EP - 352 PB - John Wiley & Sons, Ltd. VL - 25 IS - 4 SN - 0960-7692, 0960-7692 KW - Biotechnology and Bioengineering Abstracts KW - Amniotic fluid KW - Gynecology KW - Sludges KW - Statistical analysis KW - Survival KW - Morbidity KW - Pregnancy KW - Intensive care units KW - Risk factors KW - Gestation KW - Regression analysis KW - Chorioamnionitis KW - Neonates KW - Cervix KW - Obstetrics KW - Ultrasound KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19432416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ultrasound+in+Obstetrics+and+Gynecology&rft.atitle=The+prevalence+and+clinical+significance+of+amniotic+fluid+%27sludge%27+in+patients+with+preterm+labor+and+intact+membranes&rft.au=Espinoza%2C+J%3BGoncalves%2C+L+F%3BRomero%2C+R%3BNien%2C+J+K%3BStites%2C+S%3BKim%2C+Y+M%3BHassan%2C+S%3BGomez%2C+R%3BYoon%2C+B+H%3BChaiworapongsa%2C+T%3BLee%2C+W%3BMazor%2C+M&rft.aulast=Espinoza&rft.aufirst=J&rft.date=2005-04-01&rft.volume=25&rft.issue=4&rft.spage=346&rft.isbn=&rft.btitle=&rft.title=Ultrasound+in+Obstetrics+and+Gynecology&rft.issn=09607692&rft_id=info:doi/10.1002%2Fuog.1871 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sludges; Neonates; Chorioamnionitis; Pregnancy; Ultrasound; Morbidity; Amniotic fluid; Survival; Gynecology; Gestation; Risk factors; Obstetrics; Statistical analysis; Intensive care units; Regression analysis; Cervix DO - http://dx.doi.org/10.1002/uog.1871 ER - TY - JOUR T1 - Safety and Efficacy of the Nicotine Patch and Gum for the Treatment of Adolescent Tobacco Addiction AN - 17873862; 6267823 AB - OBJECTIVES: To determine the safety and efficacy of the nicotine patch and gum for adolescents who want to quit smoking. DESIGN: Double-blind, double-dummy, randomized, 3-arm trial with a nicotine patch (21 mg), nicotine gum (2 and 4 mg), or a placebo patch and gum; all participants received cognitive-behavioral group therapy. SETTING: Inner-city, outpatient clinic on the East Coast. SUBJECTS: Thirteen- to 17-year-old adolescents who smoked greater than or equal to 10 cigarettes per day (CPD), scored greater than or equal to 5 on the Fagerstroem Test of Nicotine Dependence, and were motivated to quit smoking. INTERVENTION: Twelve weeks of nicotine patch or gum therapy with cognitive-behavioral therapy, with a follow-up visit at 6 months (3 months after the end of treatment). MAIN OUTCOME MEASURES: Safety assessed on the basis of adverse event reports for all 3 groups, prolonged abstinence, assessed through self-report and verified with exhaled carbon monoxide (CO) levels of less than or equal to 6 ppm, in intent-to-treat analyses, and smoking reduction (CPD and thiocyanate concentrations) among trial completers. RESULTS: A total of 120 participants were randomized (72% white, 70% female; age: 15.2 plus or minus 1.33 years; smoking: 18.8 plus or minus 8.56 CPD; Fagerstroem Test of Nicotine Dependence score: 7.04 plus or minus 1.29) from 1999 to 2003. Participants started smoking at 11.2 plus or minus 1.98 years of age and had been smoking daily for 2.66 plus or minus 1.56 years; 75% had at least 1 current psychiatric diagnosis. Mean compliance across groups was higher for the patch (mean: 78.4-82.8%) than for the gum (mean: 38.5-50.7%). Both the patch and gum were well tolerated, and adverse events were similar to those reported in adult trials. Changes in mean saliva cotinine concentrations throughout treatment were not statistically significant. Intent-to-treat analyses of all randomized participants showed CO-confirmed prolonged abstinence rates of 18% for the active-patch group, 6.5% for the active-gum group, and 2.5% for the placebo group; the difference between the active-patch and placebo arms was statistically significant. There was no significant effect of patch versus gum or gum versus placebo on cessation outcomes. Abstinence rates at the 3-month follow-up assessment were sustained but were not significantly associated with treatment group. Mean smoking rates, but not CO or thiocyanate concentrations, decreased significantly in all 3 arms but not as a function of treatment group. CONCLUSIONS: Nicotine patch therapy combined with cognitive-behavioral intervention was effective, compared with placebo, for treatment of tobacco dependence among adolescent smokers. Decreases in the numbers of cigarettes smoked appeared to be offset by compensatory smoking. Additional study of nicotine gum, with enhanced instructional support, is needed to assess its efficacy among adolescent smokers. JF - Pediatrics AU - Moolchan, Eric T AU - Robinson, Miqun L AU - Ernst, Monique AU - Cadet, Jean Lud AU - Pickworth, Wallace B AU - Heishman, Stephen J AU - Schroeder, Jennifer R AD - Teen Tobacco Addiction Research Clinic, Clinical Pharmacology and Therapeutics Research Branch, National Institute on Drug Abuse, Baltimore, Maryland Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - e407 EP - e414 PB - American Academy of Pediatrics, 141 Northwest Point Blvd. Elk Grove Village IL 60007-1098 USA, [mailto:journals@aap.org], [URL:http://www.aap.org] VL - 115 IS - 4 SN - 0031-4005, 0031-4005 KW - nicotine patch KW - Health & Safety Science Abstracts KW - Prevention KW - Nicotine KW - Cigarette smoking KW - Tobacco KW - Side effects KW - Adolescents KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17873862?accountid=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=Pediatrics&rft.atitle=Safety+and+Efficacy+of+the+Nicotine+Patch+and+Gum+for+the+Treatment+of+Adolescent+Tobacco+Addiction&rft.au=Moolchan%2C+Eric+T%3BRobinson%2C+Miqun+L%3BErnst%2C+Monique%3BCadet%2C+Jean+Lud%3BPickworth%2C+Wallace+B%3BHeishman%2C+Stephen+J%3BSchroeder%2C+Jennifer+R&rft.aulast=Moolchan&rft.aufirst=Renata&rft.date=2005-04-01&rft.volume=57&rft.issue=4-5&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=IUBMB+life&rft.issn=15216543&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 - Nicotine; Adolescents; Prevention; Cigarette smoking; Tobacco; Side effects ER - TY - JOUR T1 - Cross-Resistance of Escherichia coli RNA Polymerases Conferring Rifampin Resistance to Different Antibiotics AN - 17872740; 6245818 AB - In this study we further defined the rifampin-binding sites in Escherichia coli RNA polymerase (RNAP) and determined the relationship between rifampin-binding sites and the binding sites of other antibiotics, including two rifamycin derivatives, rifabutin and rifapentine, and streptolydigin and sorangicin A, which are unrelated to rifampin, using a purified in vitro system. We found that there is almost a complete correlation between resistance to rifampin (Rif super(r)) and reduced rifampin binding to 12 RNAPs purified from different rpoB Rif super(r) mutants and a complete cross-resistance among the different rifamycin derivatives. Most Rif super(r) RNAPs were sensitive to streptolydigin, although some exhibited weak resistance to this antibiotic. However, 5 out of the 12 Rif super(r) RNAPs were partially resistant to sorangicin A, and one was completely cross-resistant to sorangicin A, indicating that the binding site(s) for these two antibiotics overlaps. Both rifampin and sorangicin A inhibited the transition step between transcription initiation and elongation; however, longer abortive initiation products were produced in the presence of the latter, indicating that the binding site for sorangicin A is within the rifampin-binding site. Competition experiments of different antibiotics with super(3)H-labeled rifampin for binding to wild-type RNAP further confirmed that the binding sites for rifampin, rifabutin, rifapentine, and sorangicin A are shared, whereas the binding sites for rifampin and streptolydigin are distinct. Because Rif super(r) mutations are highly conserved in eubacteria, our results indicate that this set of Rif super(r) mutant RNAPs can be used to screen for new antibiotics that will inhibit the growth of Rif super(r) pathogenic bacteria. JF - Journal of Bacteriology AU - Xu, Ming AU - Zhou, Yan Ning AU - Goldstein, Beth P AU - Jin, Ding Jun AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute-Frederick, National Institutes of Health, Frederick. Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Lepetit Research Center, Gerenzano, Varese, Italy Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 2783 EP - 2792 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 187 IS - 8 SN - 0021-9193, 0021-9193 KW - rifapentine KW - sorangicin A KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Rifampin KW - DNA-directed RNA polymerase KW - Rifabutin KW - Escherichia coli KW - Cross-resistance KW - Rifamycins KW - Competition KW - Mutation KW - Antibiotic resistance KW - Transcription initiation KW - rpoB gene KW - N 14090:RNA: Ribozymes, Ribonucleoproteins, RNA-binding protein KW - J 02795:Antibiotic resistance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17872740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cross-Resistance+of+Escherichia+coli+RNA+Polymerases+Conferring+Rifampin+Resistance+to+Different+Antibiotics&rft.au=Xu%2C+Ming%3BZhou%2C+Yan+Ning%3BGoldstein%2C+Beth+P%3BJin%2C+Ding+Jun&rft.aulast=Xu&rft.aufirst=Ming&rft.date=2005-04-01&rft.volume=187&rft.issue=8&rft.spage=2783&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Rifampin; DNA-directed RNA polymerase; Rifabutin; Mutation; Competition; Rifamycins; Cross-resistance; Antibiotic resistance; rpoB gene; Transcription initiation; Escherichia coli ER - TY - JOUR T1 - Infrared spectroscopic imaging for histopathologic recognition AN - 17865475; 6251079 AB - The process of histopathology, comprising tissue staining and morphological pattern recognition, has remained largely unchanged for over 140 years. Although it is integral to clinical and research activities, histopathologic recognition remains a time-consuming, subjective process to which only limited statistical confidence can be assigned because of inherent operator variability. Although immunohistochemical approaches allow limited molecular detection, significant challenges remain in using them for quantitative, automated pathology. Vibrational spectroscopic approaches, by contrast, directly provide nonperturbing molecular descriptors, but a practical spectroscopic protocol for histopathology is lacking. Here we couple high-throughput Fourier transform infrared (FTIR) spectroscopic imaging of tissue microarrays with statistical pattern recognition of spectra indicative of endogenous molecular composition and demonstrate histopathologic characterization of prostatic tissue. This automated histologic segmentation is applied to routine archival tissue samples, incorporates well-defined tests of statistical significance and eliminates any requirement for dyes or molecular probes. Finally, we differentiate benign from malignant prostatic epithelium by spectroscopic analyses. JF - Nature Biotechnology AU - Fernandez, Daniel C AU - Bhargava, Rohit AU - Hewitt, Stephen M AU - Levin, Ira W AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892- 0520, USA., iwl@helix.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 469 EP - 474 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 23 IS - 4 SN - 1087-0156, 1087-0156 KW - histopathology KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Statistics KW - IR spectroscopy KW - Statistical analysis KW - imaging KW - Pattern recognition KW - Dyes KW - Epithelium KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17865475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Bacteriology&rft.atitle=Surprising+Dependence+on+Postsegregational+Killing+of+Host+Cells+for+Maintenance+of+the+Large+Virulence+Plasmid+of+Shigella+flexneri&rft.au=Sayeed%2C+Sameera%3BBrendler%2C+Therese%3BDavis%2C+Michael%3BReaves%2C+Lucretia%3BAustin%2C+Stuart&rft.aulast=Sayeed&rft.aufirst=Sameera&rft.date=2005-04-01&rft.volume=187&rft.issue=8&rft.spage=2768&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Statistics; imaging; Pattern recognition; Epithelium; Dyes; Statistical analysis; IR spectroscopy DO - http://dx.doi.org/10.1038/nbt1080 ER - TY - JOUR T1 - Polygenic Effects and Cigarette Smoking Account for a Portion of the Familial Aggregation of Nuclear Sclerosis AN - 17846192; 6244013 AB - Cataract is the most common cause of blindness worldwide. Nuclear cataract, an advanced stage of nuclear sclerosis, is the most common type of age-related cataract. The authors assessed data from 2,089 persons within 620 extended pedigrees who participated in the 1988-1990 Beaver Dam Eye Study in Wisconsin to determine whether the observed familial aggregation of nuclear sclerosis could be explained by inheritance of a major gene. Familial correlations were examined and segregation analyses were performed on nuclear sclerosis measurements adjusted for age, sex, and pack-years of cigarette smoking. There was modest correlation among close family members after adjustment for age, sex, and pack-years of cigarette smoking: 0.084 between parents and offspring, and 0.198 between sibling pairs. Although results do not support involvement of a single major locus in the etiology of nuclear sclerosis, models that allowed for familial correlation, attributable in part to polygenic effects, did provide a better fit to the observed data than models without a polygenic effect. This finding suggests that several genes of modest effect may influence development of nuclear lens opacity, possibly in conjunction with environmental factors. Cigarette smoking was an important covariate in these analyses. Overall, results highlight the complex etiology of nuclear sclerosis. JF - American Journal of Epidemiology AU - Klein, Alison P AU - Duggal, Priya AU - Lee, Kristine E AU - O'Neill, Jennifer A AU - Klein, Ronald AU - Bailey-Wilson, Joan E AU - Klein, Barbara EK AD - Statistical Genetics Section, Inherited Disease Research Branch, National Human Genome Research Institute, Baltimore, MD Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 707 EP - 713 PB - Oxford University Press, Oxford Journals Health, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 161 IS - 8 SN - 0002-9262, 0002-9262 KW - Toxicology Abstracts KW - Etiology KW - Heredity KW - Cataracts KW - Cigarette smoking KW - Eye lens KW - Siblings KW - Progeny KW - Sclerosis KW - Blindness KW - Environmental factors KW - Polygenic inheritance KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17846192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Polygenic+Effects+and+Cigarette+Smoking+Account+for+a+Portion+of+the+Familial+Aggregation+of+Nuclear+Sclerosis&rft.au=Klein%2C+Alison+P%3BDuggal%2C+Priya%3BLee%2C+Kristine+E%3BO%27Neill%2C+Jennifer+A%3BKlein%2C+Ronald%3BBailey-Wilson%2C+Joan+E%3BKlein%2C+Barbara+EK&rft.aulast=Klein&rft.aufirst=Alison&rft.date=2005-04-01&rft.volume=161&rft.issue=8&rft.spage=707&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 - Sclerosis; Cigarette smoking; Cataracts; Polygenic inheritance; Etiology; Heredity; Progeny; Siblings; Blindness; Environmental factors; Eye lens ER - TY - JOUR T1 - Chlamydial Infection Induces Pathobiotype-Specific Protein Tyrosine Phosphorylation in Epithelial Cells AN - 17827903; 6188724 AB - Members of the genus Chlamydia are strict obligate intracellular pathogens that exhibit marked differences in host range and tissue tropism despite sharing a remarkable level of genomic synteny. These pathobiotype differences among chlamydiae are also mirrored in their early interactions with cultured mammalian host cells. Chlamydial attachment and entry is known to trigger protein tyrosine phosphorylation. In this study, we examined the kinetics and pattern of protein tyrosine phosphorylation induced by infection with a comprehensive collection of chlamydial strains exhibiting diversity in host, tissue, and disease tropisms. We report new findings showing that protein tyrosine phosphorylation patterns induced by infection directly correlate with the pathobiotype of the infecting organism. Patterns of protein tyrosine phosphorylation were induced following early infection that unambiguously categorized chlamydial pathobiotypes into four distinct groups: (i) Chlamydia trachomatis trachoma biovars (serovars A to H), (ii) C. trachomatis lymphogranuloma venereum biovars (serovars L1 to L3), (iii) C. muridarum, and (iv) C. pneumoniae and C. caviae. Notably, chlamydia- infected murine and human epithelial cells exhibited the same protein tyrosine phosphorylation patterns; this is indirect evidence suggesting that the phosphorylated protein(s) is of chlamydial origin. If our hypothesis is correct, these heretofore-uncharacterized proteins may represent a novel class of bacterial molecules that influence pathogen-host range or tissue tropism. JF - Infection and Immunity AU - Virok, Dezso P AU - Nelson, David E AU - Whitmire, William M AU - Crane, Deborah D AU - Goheen, Morgan M AU - Caldwell, Harlan D AD - Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 1939 EP - 1946 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 73 IS - 4 SN - 0019-9567, 0019-9567 KW - Microbiology Abstracts B: Bacteriology KW - Synteny KW - Epithelial cells KW - Host range KW - Lymphogranuloma venereum KW - Tropism KW - Tyrosine KW - Chlamydia trachomatis KW - Pathogens KW - Trachoma KW - Phosphorylation KW - Kinetics KW - genomics KW - J 02849:Sexually-transmitted diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17827903?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chlamydial+Infection+Induces+Pathobiotype-Specific+Protein+Tyrosine+Phosphorylation+in+Epithelial+Cells&rft.au=Virok%2C+Dezso+P%3BNelson%2C+David+E%3BWhitmire%2C+William+M%3BCrane%2C+Deborah+D%3BGoheen%2C+Morgan+M%3BCaldwell%2C+Harlan+D&rft.aulast=Virok&rft.aufirst=Dezso&rft.date=2005-04-01&rft.volume=73&rft.issue=4&rft.spage=1939&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Phosphorylation; Tyrosine; Tropism; Epithelial cells; Host range; Pathogens; Lymphogranuloma venereum; genomics; Kinetics; Synteny; Trachoma ER - TY - JOUR T1 - Early Role of CD4 super(+) Th1 Cells and Antibodies in HER-2 Adenovirus Vaccine Protection against Autochthonous Mammary Carcinomas AN - 17815458; 6190561 AB - HER-2 is an oncogenic tumor-associated Ag that is overexpressed in several human tumors including breast and ovarian cancer. The efficacy and mechanism of a HER-2-expressing recombinant adenoviral vaccine to protect against tumorigenesis was examined using HER-2 transgenic (BALB-neuT) mice, which develop spontaneous breast tumors in all 10 mammary glands, and also using a transplantable mouse tumor model. Vaccination beginning at 6-8 wk of age (through 19 wk of age) prevented development of spontaneous mammary tumors even after 50 wk, whereas the animals in the control groups had tumors in all mammary glands by 25 wk. Such long-term protection after the last boost has not been achieved previously in this transgenic mouse in which the oncogene is continuously spawning tumorigenesis. Using beta sub(2)-microglobulin-knockout, IFN- gamma -knockout, and B cell-deficient mice, CD4 super(+) and CD8 super(+) cell depletion, and Ab transfer studies, we show that induction of anti-HER-2/neu Abs are both necessary and sufficient for protection, and the IgG2a isotype is most effective. In contrast, CD8 super(+) T cells are not necessary at all, and CD4 super(+) T cells are necessary for only 36-48 h after immunization to provide help for B cells but not as effector cells. Equal protection in immunized mice deficient in Fc gamma RI/III excluded an FcR-mediated mechanism. Anti-HER-2 serum not only inhibited growth of mammary tumor cell lines expressing HER-2 in vitro but also protected mice from tumors in vivo, suggesting a direct action of Ab on the tumor cells. Such a vaccine may provide Ab-mediated protection against HER-2- expressing breast cancers in humans. JF - Journal of Immunology AU - Park, Jong Myun AU - Terabe, Masaki AU - Sakai, Yoshio AU - Munasinghe, Jeeva AU - Forni, Guido AU - Morris, John C AU - Berzofsky, Jay A AD - Vaccine Branch and Cancer Gene Therapy Section, Metabolism Branch, Center for Cancer Research, National Cancer Institute, and Mouse Imaging Facility, National Institute of Neurological Disorders and Stroke, Bethesda, MD Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 4228 EP - 4236 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 174 IS - 7 SN - 0022-1767, 0022-1767 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Tumor cells KW - CD4 antigen KW - HER2 protein KW - Oncogenes KW - Lymphocytes T KW - Lymphocytes B KW - Mammary gland KW - Tumorigenesis KW - Adenovirus KW - CD8 antigen KW - Transgenic mice KW - Antibodies KW - Breast cancer 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/17815458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Early+Role+of+CD4+super%28%2B%29+Th1+Cells+and+Antibodies+in+HER-2+Adenovirus+Vaccine+Protection+against+Autochthonous+Mammary+Carcinomas&rft.au=Park%2C+Jong+Myun%3BTerabe%2C+Masaki%3BSakai%2C+Yoshio%3BMunasinghe%2C+Jeeva%3BForni%2C+Guido%3BMorris%2C+John+C%3BBerzofsky%2C+Jay+A&rft.aulast=Park&rft.aufirst=Jong&rft.date=2005-04-01&rft.volume=174&rft.issue=7&rft.spage=4228&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Mammary gland; HER2 protein; CD4 antigen; Lymphocytes T; Antibodies; CD8 antigen; Tumorigenesis; Lymphocytes B; Breast cancer; Transgenic mice; Tumor cells; Oncogenes ER - TY - JOUR T1 - Maintenance of Pulmonary Th1 Effector Function in Chronic Tuberculosis Requires Persistent IL-12 Production AN - 17770847; 6190555 AB - The mechanisms that prevent reactivation of latent Mycobacterium tuberculosis infection in asymptomatic individuals are poorly understood. Although IL-12 is critical for the induction of IFN- gamma -dependent host control of M. tuberculosis, the requirement for the cytokine in the maintenance of host resistance and pulmonary Th1 effector function has not yet been formally examined. In this study, we reconstituted IL-12p40-deficient mice with IL-12 during the first 4 wk of infection and then assessed the effects of cytokine withdrawal. Although IL-12 administration initially resulted in restricted mycobacterial growth and prolonged survival, the reconstituted animals eventually succumbed to infection. This breakdown in bacterial control was accompanied by a marked reduction in the numbers of IFN- gamma -producing CD4 super(+) T cells in lungs. Moreover, whereas CD4 super(+) T cells isolated from chronically infected wild-type mice expanded and transferred long-term protection to M. tuberculosis-challenged RAG super(-/-) mice, they failed to do so in IL-12p40- deficient RAG super(-/-) recipients and were clearly reduced in frequency within pulmonary granulomas in the latter animals. These studies establish that continuous IL-12 production is necessary for maintenance of the pulmonary Th1 cells required for host control of persistent M. tuberculosis infection and suggest that breakdown of this mechanism could be a contributing factor in reactivated disease. JF - Journal of Immunology AU - Feng, Carl G AU - Jankovic, Dragana AU - Kullberg, Marika AU - Cheever, Allen AU - Scanga, Charles A AU - Hieny, Sara AU - Caspar, Patricia AU - Yap, George S AU - Sher, Alan AD - Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 4185 EP - 4192 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 174 IS - 7 SN - 0022-1767, 0022-1767 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - g-Interferon KW - Helper cells KW - Granuloma KW - Infection KW - Interleukin 12 KW - CD4 antigen KW - ^g-Interferon KW - Lung KW - Lymphocytes T KW - Tuberculosis KW - Mycobacterium tuberculosis KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17770847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Maintenance+of+Pulmonary+Th1+Effector+Function+in+Chronic+Tuberculosis+Requires+Persistent+IL-12+Production&rft.au=Feng%2C+Carl+G%3BJankovic%2C+Dragana%3BKullberg%2C+Marika%3BCheever%2C+Allen%3BScanga%2C+Charles+A%3BHieny%2C+Sara%3BCaspar%2C+Patricia%3BYap%2C+George+S%3BSher%2C+Alan&rft.aulast=Feng&rft.aufirst=Carl&rft.date=2005-04-01&rft.volume=174&rft.issue=7&rft.spage=4185&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Interleukin 12; Lymphocytes T; Infection; Lung; Tuberculosis; Helper cells; g-Interferon; CD4 antigen; Granuloma; ^g-Interferon ER - TY - JOUR T1 - Genetic polymorphisms: Impact on the risk of fetal alcohol spectrum disorders AN - 17658386; 6486803 AB - Clinical reports on monozygotic and dizygotic twins provided the initial evidence for the involvement of genetic factors in risk vulnerability for fetal alcohol spectrum disorders (FASD) including fetal alcohol syndrome (FAS). Research with selectively bred and inbred rodents, genetic crosses of these lines and strains, and embryo culture studies have further clarified the role of both maternal and fetal genetics in the development of FASD. Research to identify specific polymorphisms contributing to FASD is still at an early stage. To date, polymorphisms of only one of the genes for the alcohol dehydrogenase enzyme family, the ADH1B, have been demonstrated to contribute to FASD vulnerability. In comparison with ADH1B*1, both maternal and fetal ADH1B*2 have been shown to reduce risk for FAS in a mixed ancestry South African population. ADH1B*3 appears to afford protection for FASD outcomes in African-American populations. Other candidate genes should be examined with respect to FASD risk, including those for the enzymes of serotonin metabolism, in particular the serotonin transporter. By its very nature, alcohol teratogenesis is the expression of the interaction of genes with environment. The study of genetic factors. JF - Birth Defects Research Part A: Clinical and Molecular Teratology AU - Warren, K R AU - Li, T-K AD - National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane MSC 9304, Suite 2005, Bethesda, MD 20892-9304, USA, kw46m@nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 195 EP - 203 VL - 73 IS - 4 SN - 1542-0752, 1542-0752 KW - Toxicology Abstracts; Genetics Abstracts KW - X 24180:Social poisons & drug abuse KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17658386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=The+Molecular+Chaperone%2C+ClpA%2C+Has+a+Single+High+Affinity+Peptide+Binding+Site+per+Hexamer&rft.au=Piszczek%2C+Grzegorz%3BRozycki%2C+Jan%3BSingh%2C+Satyendra+K%3BGinsburg%2C+Ann%3BMaurizi%2C+Michael+R&rft.aulast=Piszczek&rft.aufirst=Grzegorz&rft.date=2005-04-01&rft.volume=280&rft.issue=13&rft.spage=12221&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Use of housekeeping gene sequencing for species identification of viridans streptococci AN - 17654360; 6445287 AB - Based on the genetic analysis of 20 reference strains, we describe an approach using the sequencing of 2 housekeeping genes, zwf and gki, to identify members of the mitis-sanguinis group of viridans streptococci to the species level, with a better discrimination compared with 16S rDNA sequencing. This approach also suggested that some reference strains may not be correctly classified. JF - Diagnostic Microbiology and Infectious Disease AU - Kiratisin, P AU - Li, L AU - Murray, PR AU - Fischer, SH AD - Department of Microbiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, sfischer@cc.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 297 EP - 301 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 51 IS - 4 SN - 0732-8893, 0732-8893 KW - streptococci KW - Microbiology Abstracts B: Bacteriology KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17654360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diagnostic+Microbiology+and+Infectious+Disease&rft.atitle=Use+of+housekeeping+gene+sequencing+for+species+identification+of+viridans+streptococci&rft.au=Kiratisin%2C+P%3BLi%2C+L%3BMurray%2C+PR%3BFischer%2C+SH&rft.aulast=Kiratisin&rft.aufirst=P&rft.date=2005-04-01&rft.volume=51&rft.issue=4&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=Diagnostic+Microbiology+and+Infectious+Disease&rft.issn=07328893&rft_id=info:doi/10.1016%2Fj.diagmicrobio.2004.12.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-10-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.diagmicrobio.2004.12.001 ER - TY - JOUR T1 - Global Transcriptional Programs Reveal a Carbon Source Foraging Strategy by Escherichia coli AN - 17620981; 6274508 AB - By exploring global gene expression of Escherichia coli growing on six different carbon sources, we discovered a striking genome transcription pattern: as carbon substrate quality declines, cells systematically increase the number of genes expressed. Gene induction occurs in a hierarchical manner and includes many factors for uptake and metabolism of better but currently unavailable carbon sources. Concomitantly, cells also increase their motility. Thus, as the growth potential of the environment decreases, cells appear to devote progressively more energy on the mere possibility of improving conditions. This adaptation is not what would be predicated by classic regulatory models alone. We also observe an inverse correlation between gene activation and rRNA synthesis suggesting that reapportioning RNA polymerase (RNAP) contributes to the expanded genome activation. Significant differences in RNAP distribution in vivo, monitored using an RNAP-green fluorescent protein fusion, from energy-rich and energy-poor carbon source cultures support this hypothesis. Together, these findings represent the integration of both substrate-specific and global regulatory systems, and may be a bacterial approximation to metazoan risk-prone foraging behavior. JF - Journal of Biological Chemistry AU - Liu, Mingzhu AU - Durfee, Tim AU - Cabrera, Julio E AU - Zhao, Kai AU - Jin, Ding J AU - Blattner, Frederick R AD - Department of Genetics and McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wisconsin 53706 and the Transcription Control Section, Gene Regulation and Chromosome Biology Laboratory, Center for Cancer Research, NCI at Frederick, National Institutes of Health, Frederick, Maryland 21702 Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 15921 EP - 15927 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 - 280 IS - 16 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - J 02726:RNA and ribosomes KW - N 14045:Transcriptional regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17620981?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Global+Transcriptional+Programs+Reveal+a+Carbon+Source+Foraging+Strategy+by+Escherichia+coli&rft.au=Liu%2C+Mingzhu%3BDurfee%2C+Tim%3BCabrera%2C+Julio+E%3BZhao%2C+Kai%3BJin%2C+Ding+J%3BBlattner%2C+Frederick+R&rft.aulast=Liu&rft.aufirst=Mingzhu&rft.date=2005-04-01&rft.volume=280&rft.issue=16&rft.spage=15921&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Systematic variation normalization in microarray data to get gene expression comparison unbiased AN - 17574477; 6386147 AB - Normalization removes or minimizes the biases of systematic variation that exists in experimental data sets. This study presents a systematic variation normalization (SVN) procedure for removing systematic variation in two channel microarray gene expression data. Based on an analysis of how systematic variation contributes to variability in microarray data sets, our normalization procedure includes background subtraction determined from the distribution of pixel intensity values from each data acquisition channel and log conversion, linear or non-linear regression, restoration or transformation, and multiarray normalization. In the case when a non-linear regression is required, an empirical polynomial approximation approach is used. Either the high terminated points or their averaged values in the distributions of the pixel intensity values observed in control channels may be used for rescaling multiarray datasets. These pre-processing steps remove systematic variation in the data attributable to variability in microarray slides, assay-batches, the array process, or experimenters. Biologically meaningful. JF - Journal of Bioinformatics and Computational Biology AU - Chou, J W AU - Paules, R S AU - Bushel, PR AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA, chou@nichs.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 225 EP - 241 VL - 3 IS - 2 SN - 0219-7200, 0219-7200 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Gene expression KW - Databases KW - Mathematical models KW - Data processing KW - Bioinformatics KW - DNA microarrays KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17574477?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Bioinformatics+and+Computational+Biology&rft.atitle=Systematic+variation+normalization+in+microarray+data+to+get+gene+expression+comparison+unbiased&rft.au=Chou%2C+J+W%3BPaules%2C+R+S%3BBushel%2C+PR&rft.aulast=Chou&rft.aufirst=J&rft.date=2005-04-01&rft.volume=3&rft.issue=2&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bioinformatics+and+Computational+Biology&rft.issn=02197200&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Data processing; DNA microarrays; Gene expression; Databases; Mathematical models; Bioinformatics ER - TY - JOUR T1 - Effects of Electron-Beam Irradiation on Whole Genome Amplification AN - 17540509; 6269758 AB - Electron-beam (E-beam) irradiation, currently being used to sterilize mail addressed to selected ZIP codes in the United States, has significant negative effects on the genomic integrity of DNA extracted from buccal-cell washes. We investigated the yield, composition, and genotyping performance of whole genome amplified DNA (wgaDNA) derived from 24 matched samples of E-beam-irradiated and nonirradiated genomic DNA (gDNA) as a model for the effects of degraded gDNA on the performance of whole genome amplification. gDNA was amplified using the Multiple Displacement Amplification method. Three methods of DNA quantification analysis were used to estimate the yield and composition of wgaDNA, and 65 short tandem repeat and single nucleotide polymorphism genotyping assays were used to evaluate the genotyping performance of irradiated and nonirradiated gDNA and wgaDNA. Compared with wgaDNA derived from nonirradiated gDNA, wgaDNA derived from irradiated gDNA exhibited a significantly reduced yield of wgaDNA and significantly reduced short tandem repeat and single nucleotide polymorphism genotyping completion and concordance rates (P < 0.0001). Increasing the amount of irradiated gDNA input into whole genome amplification improved genotyping performance of wgaDNA but not to the level of wgaDNA derived from nonirradiated gDNA. Multiple Displacement Amplification wgaDNA derived from E-beam-irradiated gDNA is not suitable for genotyping analysis. JF - Cancer Epidemiology, Biomarkers & Prevention AU - Bergen, Andrew W AU - Qi, Ying AU - Haque, Kashif A AU - Welch, Robert A AU - Garcia-Closas, Montserrat AU - Chanock, Stephen J AU - Vaught, Jim AU - Castle, Philip E AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 1016 EP - 1019 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 14 IS - 4 SN - 1055-9965, 1055-9965 KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Genomes KW - Short tandem repeats KW - Radiation KW - Single-nucleotide polymorphism KW - Genotyping KW - DNA KW - genomics KW - biomarkers KW - Models KW - X 24210:Radiation & radioactive materials KW - N 14020:DNA/RNA genomics sequence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17540509?accountid=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+Epidemiology%2C+Biomarkers+%26+Prevention&rft.atitle=Effects+of+Electron-Beam+Irradiation+on+Whole+Genome+Amplification&rft.au=Bergen%2C+Andrew+W%3BQi%2C+Ying%3BHaque%2C+Kashif+A%3BWelch%2C+Robert+A%3BGarcia-Closas%2C+Montserrat%3BChanock%2C+Stephen+J%3BVaught%2C+Jim%3BCastle%2C+Philip+E&rft.aulast=Bergen&rft.aufirst=Andrew&rft.date=2005-04-01&rft.volume=14&rft.issue=4&rft.spage=1016&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Genomes; Short tandem repeats; Radiation; Single-nucleotide polymorphism; Genotyping; DNA; genomics; biomarkers; Models ER - TY - JOUR T1 - A structure-based method for protein sequence alignment AN - 17540433; 6244425 AB - MOTIVATION: With the continuing rapid growth of protein sequence data, protein sequence comparison methods have become the most widely used tools of bioinformatics. Among these methods are those that use position-specific scoring matrices (PSSMs) to describe protein families. PSSMs can capture information about conserved patterns within families, which can be used to increase the sensitivity of searches for related sequences. Certain types of structural information, however, are not generally captured by PSSM search methods. Here we introduce a program, Structure-based ALignment TOol (SALTO), that aligns protein query sequences to PSSMs using rules for placing and scoring gaps that are consistent with the conserved regions of domain alignments from NCBI's Conserved Domain Database. RESULTS: In most cases, the alignment scores obtained using the local alignment version follow an extreme value distribution. SALTO's performance in finding related sequences and producing accurate alignments is similar to or better than that of IMPALA; one advantage of SALTO is that it imposes an explicit gapping model on each protein family. AVAILABILITY: A stand-alone version of the program that can generate global or local alignments is available by ftp distribution (ftp://ftp.ncbi.nih.gov/pub/SALTO/), and has been incorporated to Cn3D structure/alignment viewer. JF - Bioinformatics AU - Kann, Maricel G AU - Thiessen, Paul A AU - Panchenko, Anna R AU - Schaeffer, Alejandro A AU - Altschul, Stephen F AU - Bryant, Stephen H AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Department of Health and Human Services Bethesda, MD 20894, USA, bryant@ncbi.nlm.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 1451 EP - 1456 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 21 IS - 8 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Protein structure KW - Computer programs KW - Databases KW - protein families KW - Bioinformatics 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/17540433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+structure-based+method+for+protein+sequence+alignment&rft.au=Kann%2C+Maricel+G%3BThiessen%2C+Paul+A%3BPanchenko%2C+Anna+R%3BSchaeffer%2C+Alejandro+A%3BAltschul%2C+Stephen+F%3BBryant%2C+Stephen+H&rft.aulast=Kann&rft.aufirst=Maricel&rft.date=2005-04-01&rft.volume=21&rft.issue=8&rft.spage=1451&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Amino acid sequence; protein families; Bioinformatics; Databases; Computer programs; Protein structure ER - TY - JOUR T1 - Surprising Dependence on Postsegregational Killing of Host Cells for Maintenance of the Large Virulence Plasmid of Shigella flexneri AN - 17539047; 6245816 AB - Low-copy-number plasmids all encode multiple systems to ensure their propagation, including replication, partition (active segregation), and postsegregational killing (PSK) systems. PSK systems kill those rare cells that lose the plasmid due to replication or segregation errors. PSK systems should not be used as the principle means of maintaining the plasmid. The metabolic cost of killing the many cured cells that would arise from random plasmid segregation is far too high. Here we describe an interesting exception to this rule. Maintenance of the large virulence plasmid of Shigella flexneri is highly dependent on one of its PSK systems, mvp, at 37 degree C, the temperature experienced during pathogenesis. At 37 degree C, the plasmid is very unstable and mvp efficiently kills the resulting cured bacterial cells. This imposes a major growth disadvantage on the virulent bacterial population. The systems that normally ensure accurate plasmid replication and segregation are attenuated or overridden at 37 degree C. At 30 degree C, a temperature encountered by Shigella in the outside environment, the maintenance systems function normally and the plasmid is no longer dependent on mvp. We discuss why the virulent pathogen tolerates this self-destructive method of propagation at the temperature of infection. JF - Journal of Bacteriology AU - Sayeed, Sameera AU - Brendler, Therese AU - Davis, Michael AU - Reaves, Lucretia AU - Austin, Stuart AD - Gene Regulation and Chromosome Biology Laboratory, National Cancer Institute-Frederick, Frederick, Maryland. Department of Biological Sciences, Central Connecticut State University, New Britain, Connecticut Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 2768 EP - 2773 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 187 IS - 8 SN - 0021-9193, 0021-9193 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Temperature effects KW - Replication KW - Pathogens KW - Infection KW - Plasmids KW - Virulence KW - Shigella flexneri KW - N 14025:RNA/DNA role in infection & immune response KW - J 02760:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17539047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Surprising+Dependence+on+Postsegregational+Killing+of+Host+Cells+for+Maintenance+of+the+Large+Virulence+Plasmid+of+Shigella+flexneri&rft.au=Sayeed%2C+Sameera%3BBrendler%2C+Therese%3BDavis%2C+Michael%3BReaves%2C+Lucretia%3BAustin%2C+Stuart&rft.aulast=Sayeed&rft.aufirst=Sameera&rft.date=2005-04-01&rft.volume=187&rft.issue=8&rft.spage=2768&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Shigella flexneri; Plasmids; Temperature effects; Replication; Virulence; Infection; Pathogens ER - TY - JOUR T1 - Boolean relationships among genes responsive to ionizing radiation in the NCI 60 ACDS AN - 17536496; 6244437 AB - MOTIVATION: An early use of gene-expression data coming from microarrays was to discover non-linear multivariate intergene relationships. Pursuing this direction, the motivation for this paper is 2-fold: (1) to discover and elucidate multivariate logical predictive relations among gene expressions in a dataset arising from radiation studies using the NCI 60 Anti-Cancer Drug Screen (ACDS) cell lines; and (2) to demonstrate how these logical relations based on coarse quantization reflect corresponding relations in the continuous data. RESULTS: Using the coefficient of determination, a large number of logical relationships have been discovered among genes in the NCI 60 ACDS cell lines. Moreover, these relationships can be seen directly in the original continuous data, and many are robust relative to the thresholds used to obtain the logical data from the continuous data. A key observation is that a number of intergene relationships appear to be considerably stronger when p53 is functional as compared to when it is not, which is consistent with earlier findings in the literature. AVAILABILITY: The appendix is available at http://gsp.tamu.edu/Publications/supplement.htm JF - Bioinformatics AU - Pal, Ranadip AU - Datta, Aniruddha AU - Fornace, Albert JJr AU - Bittner, Michael L AU - Dougherty, Edward R AD - Department of Electrical Engineering, Texas A&M University College Station, TX 77843, USA. National Cancer Institute NIH Bethesda, MD 20892, USA. Translational Genomics Research Institute 400 North Fifth Street, Suite 1600, Phoenix, AZ 85004, USA. University of Texas M.D. Anderson Cancer Center Houston, TX 77030, USA, edward@ee.tamu.edu Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 1542 EP - 1549 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 21 IS - 8 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Gene expression KW - Ionizing radiation KW - Appendix KW - Bioinformatics KW - DNA microarrays KW - p53 protein KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17536496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Boolean+relationships+among+genes+responsive+to+ionizing+radiation+in+the+NCI+60+ACDS&rft.au=Pal%2C+Ranadip%3BDatta%2C+Aniruddha%3BFornace%2C+Albert+JJr%3BBittner%2C+Michael+L%3BDougherty%2C+Edward+R&rft.aulast=Pal&rft.aufirst=Ranadip&rft.date=2005-04-01&rft.volume=21&rft.issue=8&rft.spage=1542&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene expression; DNA microarrays; Ionizing radiation; Appendix; p53 protein; Bioinformatics ER - TY - JOUR T1 - Dynamic Fluorescent Imaging of Human Immunodeficiency Virus Type 1 Gag in Live Cells by Biarsenical Labeling AN - 17529347; 6185782 AB - Human immunodeficiency virus type 1 (HIV-1) Gag is the primary structural protein of the virus and is sufficient for particle formation. We utilized the recently developed biarsenical-labeling method to dynamically observe HIV-1 Gag within live cells by adding a tetracysteine tag (C-C-P-G-C-C) to the C terminus of Gag in both Pr55 super(Gag) expression and full-length proviral constructs. Membrane-permeable biarsenical compounds FlAsH and ReAsH covalently bond to this tetracysteine sequence and specifically fluoresce, effectively labeling Gag in the cell. Biarsenical labeling readily and specifically detected a tetracysteine-tagged HIV-1 Gag protein (Gag-TC) in HeLa, Mel JuSo, and Jurkat T cells by deconvolution fluorescence microscopy. Gag-TC was localized primarily at or near the plasma membrane in all cell types examined. Fluorescent two-color analysis of Gag-TC in HeLa cells revealed that nascent Gag was present mostly at the plasma membrane in distinct regions. Intracellular imaging of a Gag-TC myristylation mutant observed a diffuse signal throughout the cell, consistent with the role of myristylation in Gag localization to the plasma membrane. In contrast, mutation of the L-domain core sequence did not appreciably alter the localization of Gag, suggesting that the PTAP L domain functions at the site of budding rather than as a targeting signal. Taken together, our results show that Gag concentrates in specific plasma membrane areas rapidly after translation and demonstrate the utility of biarsenical labeling for visualizing the dynamic localization of Gag. JF - Journal of Virology AU - Rudner, Lynnie AU - Nydegger, Sascha AU - Coren, Lori V AU - Nagashima, Kunio AU - Thali, Markus AU - Ott, David E AD - Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont. Basic Research. Research Technology Programs, SAIC- Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 4055 EP - 4065 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 79 IS - 7 SN - 0022-538X, 0022-538X KW - HIV-1 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Virology & AIDS Abstracts KW - Translation KW - Fluorescence KW - Plasma membranes KW - Microscopy KW - Human immunodeficiency virus 1 KW - Lymphocytes T KW - Mutation KW - imaging KW - Structural proteins KW - Gag protein KW - Budding 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/17529347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dynamic+Fluorescent+Imaging+of+Human+Immunodeficiency+Virus+Type+1+Gag+in+Live+Cells+by+Biarsenical+Labeling&rft.au=Rudner%2C+Lynnie%3BNydegger%2C+Sascha%3BCoren%2C+Lori+V%3BNagashima%2C+Kunio%3BThali%2C+Markus%3BOtt%2C+David+E&rft.aulast=Rudner&rft.aufirst=Lynnie&rft.date=2005-04-01&rft.volume=79&rft.issue=7&rft.spage=4055&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Plasma membranes; imaging; Translation; Microscopy; Gag protein; Fluorescence; Budding; Lymphocytes T; Structural proteins; Mutation ER - TY - JOUR T1 - Transfer of a TCR Gene Derived from a Patient with a Marked Antitumor Response Conveys Highly Active T-Cell Effector Functions AN - 17523832; 6238009 AB - The genes for the alpha and beta chains of a highly reactive anti-MART-1 T-cell receptor were isolated from T-lymphocytes that mediated in vivo regression of tumor in a patient with metastatic melanoma. These genes were cloned and inserted into MSCV-based retroviral vectors. After transduction, greater than 50% gene transfer efficiency was demonstrated in primary T-lymphocytes stimulated by an anti-CD3 antibody. The specificity and biologic activity of TCR gene-transduced T-cells was determined by cytokine production after coculture of T-cells with stimulator cells pulsed with MART-1 peptide. The production of interferon- gamma and granulocyte macrophage-colony stimulating factor (GM-CSF) was comparable to highly active MART-1 specific peripheral blood lymphocytes (PBL) in the amount of cytokine produced and transduced cells recognized peptide pulsed cells at dilutions similar to cytotoxic T lymphocyte (CTL) clones. Human leukocyte antigen (HLA) class I restricted recognition was demonstrated by mobilization of degranulation marker CD107a, by cell lysis, by cytokine production, and by proliferation in the presence of HLA-A2-positive but not HLA-A2-negative melanoma cell lines. Similar data was obtained when tumor-infiltrating lymphocytes (TIL) were transduced with the TCR genes, converting previously nonreactive cells to tumor reactive cells. TCR-transduced T-cells are thus attractive candidates for evaluation in cell transfer therapies of patients with cancer. JF - Human Gene Therapy AU - Hughes AU - Yu, YYL AU - Dudley, ME AU - Zheng, Z AU - Robbins, P F AU - Li, Y AU - Wunderlich, J AU - Hawley, R G AU - Moayeri, M AU - Rosenberg, SA AU - Morgan, R A AD - National Cancer Institute Surgery Branch, National Institutes of Health, Building 10 CRC rm 3-5940, 10 Center Drive, Bethesda, MD 20892-1201, USA, rmorgan@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 457 EP - 472 VL - 16 IS - 4 SN - 1043-0342, 1043-0342 KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Histocompatibility antigen HLA KW - T-cell receptor KW - Melanoma KW - Metastases KW - Lymphocytes T KW - Cytokines KW - g-Interferon KW - Gene therapy KW - Granulocyte-macrophage colony-stimulating factor KW - Peripheral blood KW - Tumor-infiltrating lymphocytes KW - Cancer KW - Cytotoxicity KW - ^AT-cell receptor KW - Antibodies KW - MART-1 antigen KW - ^g-Interferon KW - W3 33181:Gene therapy vectors KW - G 07443:Gene therapy 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/17523832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transfer+of+a+TCR+Gene+Derived+from+a+Patient+with+a+Marked+Antitumor+Response+Conveys+Highly+Active+T-Cell+Effector+Functions&rft.au=Hughes%3BYu%2C+YYL%3BDudley%2C+ME%3BZheng%2C+Z%3BRobbins%2C+P+F%3BLi%2C+Y%3BWunderlich%2C+J%3BHawley%2C+R+G%3BMoayeri%2C+M%3BRosenberg%2C+SA%3BMorgan%2C+R+A&rft.aulast=Hughes&rft.aufirst=&rft.date=2005-04-01&rft.volume=16&rft.issue=4&rft.spage=457&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 - Lymphocytes T; T-cell receptor; Histocompatibility antigen HLA; Cytokines; MART-1 antigen; Granulocyte-macrophage colony-stimulating factor; Melanoma; g-Interferon; Antibodies; Tumor-infiltrating lymphocytes; Cancer; Gene therapy; ^AT-cell receptor; ^g-Interferon; Cytotoxicity; Peripheral blood; Metastases ER - TY - JOUR T1 - A nationwide survey of physician office visits found that inappropriate antibiotic prescriptions were issued for bacterial respiratory tract infections in ambulatory patients AN - 17502669; 6398200 AB - Correlations between probabilities of resistance and the frequencies with which antibiotics were prescribed for treating bacterial respiratory infections were examined in a nationwide ambulatory population. The data of a nationwide probability sample survey of visits to physician offices in the United States in 1999 were used to conduct this study of drug use. A clinical pharmacologist identified antibiotics prescribed during those visits using a large online database. The participating physicians diagnosed the bacterial respiratory infections. An infectious disease expert determined the probabilities of bacterial resistance from a nationwide antibiotic surveillance database. Various bacterial respiratory infections were diagnosed during 6.5% of physician office visits in 1999. One or more antibiotics were prescribed during 51.0% of those visits. The probabilities of resistance to the most frequently prescribed antibiotics varied from 20% to 40% and showed a weak positive correlation with the frequencies of antibiotic prescriptions. A significant number of inappropriate antibiotic prescriptions were issued for infections with a high probability of bacterial resistance to the prescribed antibiotics. JF - Journal of Clinical Epidemiology AU - Huang, Boji AU - Martin, S J AU - Bachmann, KA AU - He, Xuming AU - Reese, J H AU - Wei, Ying AU - Iwuagwu, C AD - Department of Health Evaluation Sciences, Penn State College of Medicine, 600 Centerview Drive, Hershey, PA 17022-0855, USA, HuangBo@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 414 EP - 420 VL - 58 IS - 4 SN - 0895-4356, 0895-4356 KW - Microbiology Abstracts B: Bacteriology KW - Databases KW - Respiratory tract diseases KW - USA KW - Infectious diseases KW - Antibiotic resistance KW - Medical personnel KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17502669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Epidemiology&rft.atitle=A+nationwide+survey+of+physician+office+visits+found+that+inappropriate+antibiotic+prescriptions+were+issued+for+bacterial+respiratory+tract+infections+in+ambulatory+patients&rft.au=Huang%2C+Boji%3BMartin%2C+S+J%3BBachmann%2C+KA%3BHe%2C+Xuming%3BReese%2C+J+H%3BWei%2C+Ying%3BIwuagwu%2C+C&rft.aulast=Huang&rft.aufirst=Boji&rft.date=2005-04-01&rft.volume=58&rft.issue=4&rft.spage=414&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Epidemiology&rft.issn=08954356&rft_id=info:doi/10.1016%2Fj.jclinepi.2004.09.006 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Respiratory tract diseases; Databases; Infectious diseases; Medical personnel; Antibiotic resistance; USA DO - http://dx.doi.org/10.1016/j.jclinepi.2004.09.006 ER - TY - JOUR T1 - The DNA minor groove binding agents Hoechst 33258 and 33342 enhance recombinant adeno-associated virus (rAAV) transgene expression AN - 17502145; 6397737 AB - Background Recombinant adeno-associated viruses (rAAV) are commonly used in pre-clinical and clinical gene transfer studies. However, the relatively slow kinetics of rAAV transgene expression complicates in vitro and in vivo experiments. Methods 293 and COS-1 cells were transduced with rAAV2-EGFP, rAAV1-EGFP, or rAAV5-EGFP. The rAAV-EGFP expression was analyzed in the presence of Hoechst 33 258 or 33 342 as a function of time and concentration by flow cytometry and fluorescent microscope. Effects of Hoechst on cell cycle populations were determined by flow cytometry. Enhanced green fluorescent protein (EGFP) expression plasmids with or without AAV inverted terminal repeats (ITR) were constructed and gene expression by transient transfection was compared in the presence of Hoechst. Results We found that Hoechst 33 258 and 33 342 increase both the level and the population of EGFP gene expressing cells, transduced by several different serotypes of rAAV-EGFP. The augmentation of rAAV-EGFP expression occurs in different cell types in a concentration-dependent manner. In addition, the Hoechst 33 258 or 33 342 mediated enhancement of rAAV gene expression correlated with an increase of cells in S phase and G2/M phases of the cell cycle. Finally, gene expression from transfected ITR-containing plasmid DNA was also enhanced by Hoechst dyes. Conclusions Our results revealed that two different, although related, DNA-binding drugs, Hoechst 33 258 and 33 342, accelerate the kinetics of rAAV transgene expression. These findings may provide the basis for more sensitive assessment of rAAV biological activity and also extend the applications of rAAV for in vivo gene transfer. JF - Journal of Gene Medicine AU - Li, L AU - Yang, L AU - Kotin, R M AD - Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bldg. 10, Rm. 7D05, 10 Center Dr., Bethesda, MD 20892, USA, kotinr@nhlbi.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 420 EP - 431 VL - 7 IS - 4 SN - 1099-498X, 1099-498X KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Cell cycle KW - Green fluorescent protein KW - Plasmids KW - Adeno-associated virus KW - Flow cytometry KW - Gene expression KW - S phase KW - Transfection KW - Gene transfer 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/17502145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Gene+Medicine&rft.atitle=The+DNA+minor+groove+binding+agents+Hoechst+33258+and+33342+enhance+recombinant+adeno-associated+virus+%28rAAV%29+transgene+expression&rft.au=Li%2C+L%3BYang%2C+L%3BKotin%2C+R+M&rft.aulast=Li&rft.aufirst=L&rft.date=2005-04-01&rft.volume=7&rft.issue=4&rft.spage=420&rft.isbn=&rft.btitle=&rft.title=Journal+of+Gene+Medicine&rft.issn=1099498X&rft_id=info:doi/10.1002%2Fjgm.681 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 expression; Flow cytometry; Plasmids; Cell cycle; Gene transfer; Transfection; S phase; Green fluorescent protein DO - http://dx.doi.org/10.1002/jgm.681 ER - TY - JOUR T1 - Active Tolerance Induction and Prevention of Autoimmune Diabetes by Immunogene Therapy Using Recombinant Adenoassociated Virus Expressing Glutamic Acid Decarboxylase 65 Peptide GAD sub(500-585) AN - 17500552; 6267133 AB - Tolerance induction of autoreactive T cells against pancreatic beta cell-specific autoantigens such as glutamic acid decarboxylase 65 (GAD65) and insulin has been attempted as a method to prevent autoimmune diabetes. In this study, we investigate whether adenoassociated virus (AAV) gene delivery of multiple immunodominant epitopes expressing GAD sub(500-585) could induce potent immune tolerance and persistently suppress autoimmune diabetes in NOD mice. A single muscle injection of 7-wk-old female NOD mice with rAAV/GAD sub(500-585) (3 x 10 super(11) IU/mouse) quantitatively reduced pancreatic insulitis and efficiently prevented the development of overt type I diabetes. This prevention was marked by the inactivation of GAD sub(500-585)-responsive T lymphocytes, the enhanced GAD sub(500-585)-specific Th2 response (characterized by increased IL-4, IL-10 production, and decreased IFN- gamma production; especially elevated anti-GAD sub(500-585) IgG1 titer; and relatively unchanged anti-GAD sub(500-585) IgG2b titer), the increased secretion of TGF- beta , and the production of protective regulatory cells. Our studies also revealed that peptides 509-528, 570-585, and 554-546 in the region of GAD sub(500-585) played important roles in rAAV/GAD sub(500-585) immunization-induced immune tolerance. These data indicate that using AAV, a vector with advantage for therapeutic gene delivery, to transfer autoantigen peptide GAD sub(500-585), can induce immunological tolerance through active suppression of effector T cells and prevent type I diabetes in NOD mice. JF - Journal of Immunology AU - Han, Gencheng AU - Li, Yan AU - Wang, Jianan AU - Wang, Renxi AU - Chen, Guojiang AU - Song, Lun AU - Xu, Ruonan AU - Yu, Ming AU - Wu, Xiaobing AU - Qian, Jiahua AU - Shen, Beifen AD - Department of Molecular Immunology, Institute of Basic Medical Sciences, and. National Lab of Molecular Virology and Genetic Engineering, Beijing, People's Republic of China. National Cancer Institute, Vaccine Branch, Bethesda, MD 20889 Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 4516 EP - 4524 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 174 IS - 8 SN - 0022-1767, 0022-1767 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Immunoregulation KW - Pancreas KW - Autoimmune diseases KW - Insulin KW - Adeno-associated virus KW - Lymphocytes T KW - g-Interferon KW - Immunological tolerance KW - Autoantigens KW - Diabetes mellitus KW - ^g-Interferon KW - Gene transfer KW - Immunoglobulin G KW - Glutamate decarboxylase KW - F 06328:Diabetes: Animal models KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17500552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Active+Tolerance+Induction+and+Prevention+of+Autoimmune+Diabetes+by+Immunogene+Therapy+Using+Recombinant+Adenoassociated+Virus+Expressing+Glutamic+Acid+Decarboxylase+65+Peptide+GAD+sub%28500-585%29&rft.au=Han%2C+Gencheng%3BLi%2C+Yan%3BWang%2C+Jianan%3BWang%2C+Renxi%3BChen%2C+Guojiang%3BSong%2C+Lun%3BXu%2C+Ruonan%3BYu%2C+Ming%3BWu%2C+Xiaobing%3BQian%2C+Jiahua%3BShen%2C+Beifen&rft.aulast=Han&rft.aufirst=Gencheng&rft.date=2005-04-01&rft.volume=174&rft.issue=8&rft.spage=4516&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adeno-associated virus; Lymphocytes T; Immunological tolerance; Diabetes mellitus; Autoimmune diseases; Pancreas; Autoantigens; Gene transfer; Glutamate decarboxylase; Immunoglobulin G; g-Interferon; Immunoregulation; Insulin; ^g-Interferon ER - TY - JOUR T1 - The Molecular Chaperone, ClpA, Has a Single High Affinity Peptide Binding Site per Hexamer AN - 17498348; 6266578 AB - Substrate recognition by Clp chaperones is dependent on interactions with motifs composed of specific peptide sequences. We studied the binding of short motif-bearing peptides to ClpA, the chaperone component of the ATP-dependent ClpAP protease of Escherichia coli in the presence of ATP gamma S and Mg super(2+) at pH 7.5. Binding was measured by isothermal titration calorimetry (ITC) using the peptide, AANDENYALAA, which corresponds to the SsrA degradation motif found at the C terminus of abnormal nascent polypeptides in vivo. One SsrA peptide was bound per hexamer of ClpA with an association constant (K sub(A)) of 5 x 10 super(6) M super(-1). Binding was also assayed by changes in fluorescence of an N-terminal dansylated SsrA peptide, which bound with the same stoichiometry of one per ClpA hexamer (K sub(A) similar to 1 x 10 super(7) M super(-1)). Similar results were obtained when ATP was substituted for ATP gamma S at 6 degree C. Two additional peptides, derived from the phage P1 RepA protein and the E. coli HemA protein, which bear different substrate motifs, were competitive inhibitors of SsrA binding and bound to ClpA hexamers with K sub(A)' > 3 x 10 super(7) M super(-1). DNS-SsrA bound with only slightly reduced affinity to deletion mutants of ClpA missing either the N-terminal domain or the C-terminal nucleotide-binding domain, indicating that the binding site for SsrA lies within the N-terminal nucleotide-binding domain. Because only one protein at a time can be unfolded and translocated by ClpA hexamers, restricting the number of peptides initially bound should avoid nonproductive binding of substrates and aggregation of partially processed proteins. JF - Journal of Biological Chemistry AU - Piszczek, Grzegorz AU - Rozycki, Jan AU - Singh, Satyendra K AU - Ginsburg, Ann AU - Maurizi, Michael R AD - Laboratory of Biochemistry, NHLBI, and the Laboratory of Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892 Y1 - 2005/04/01/ PY - 2005 DA - 2005 Apr 01 SP - 12221 EP - 12230 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 - 280 IS - 13 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts B: Bacteriology KW - Phages KW - hexamers KW - Deletion mutant KW - Fluorescence KW - ATP KW - RepA protein KW - Titration KW - Escherichia coli KW - Calorimetry KW - Proteinase KW - Chaperones KW - Magnesium KW - pH effects KW - Phage P1 KW - ClpA protein KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17498348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Molecular+Chaperone%2C+ClpA%2C+Has+a+Single+High+Affinity+Peptide+Binding+Site+per+Hexamer&rft.au=Piszczek%2C+Grzegorz%3BRozycki%2C+Jan%3BSingh%2C+Satyendra+K%3BGinsburg%2C+Ann%3BMaurizi%2C+Michael+R&rft.aulast=Piszczek&rft.aufirst=Grzegorz&rft.date=2005-04-01&rft.volume=280&rft.issue=13&rft.spage=12221&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Phages; hexamers; Fluorescence; Deletion mutant; ATP; RepA protein; Titration; Calorimetry; Chaperones; Proteinase; Magnesium; pH effects; ClpA protein; Escherichia coli; Phage P1 ER - TY - JOUR T1 - Residential Herbicide Use and Risk of Non-Hodgkin Lymphoma AN - 17494550; 6269794 AB - Context: Environmental exposure to herbicides has been hypothesized to contribute to the long-term increase in non-Hodgkin lymphoma (NHL). Objective: To estimate the effects of residential herbicide exposure on NHL risk. Design: Population-based case-control study. Setting: Iowa and metropolitan Detroit, Los Angeles, and Seattle, 1998 to 2000. Participants: NHL patients ages 20 to 74 years and unaffected residents identified by random digit dialing and Medicare eligibility files. Main Outcome Measures: Computer-assisted personal interviews (1,321 cases, 1,057 controls) elicited data on herbicide use at each home occupied since 1970. Levels of 2,4-dichlorophenoxy-acetic acid and dicamba were measured in dust taken from used vacuum cleaner bags in the current home (679 cases, 510 controls who had owned at least half of their carpets for greater than or equal to 5 years). Results: Herbicide use on the lawn or garden was similar among cases and controls (adjusted relative risk, 1.02; 95% confidence interval, 0.84-1.23). Estimated risk did not increase with greater duration, frequency, or total number of applications of herbicides to the lawn, the garden, or to both combined. Risk was not elevated for respondents who applied the herbicides themselves and not for those exposed during the 1970s, 1980s, or 1990s. We detected 2,4-dichlorophenoxy-acetic acid equally often in homes of cases and controls (78%). We found dicamba in homes of 15% of cases and 20% of controls. We also found no elevation in risk among the respondents who had the highest dust levels and highest self-reported exposures. We found no consistent patterns for specific histologies. Conclusions: We found no detectable excess associated with residential exposures. Residential herbicide exposures are unlikely to explain the long-term increase in NHL. JF - Cancer Epidemiology, Biomarkers & Prevention AU - Hartge, Patricia AU - Colt, Joanne S AU - Severson, Richard K AU - Cerhan, James R AU - Cozen, Wendy AU - Camann, David AU - Zahm, Shelia Hoar AU - Davis, Scott AD - Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 934 EP - 937 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 14 IS - 4 SN - 1055-9965, 1055-9965 KW - Toxicology Abstracts KW - Risk assessment KW - Carpets KW - Vacuum KW - Herbicides KW - biomarkers KW - Lymphoma KW - Dust KW - X 24134:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17494550?accountid=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+Epidemiology%2C+Biomarkers+%26+Prevention&rft.atitle=Residential+Herbicide+Use+and+Risk+of+Non-Hodgkin+Lymphoma&rft.au=Hartge%2C+Patricia%3BColt%2C+Joanne+S%3BSeverson%2C+Richard+K%3BCerhan%2C+James+R%3BCozen%2C+Wendy%3BCamann%2C+David%3BZahm%2C+Shelia+Hoar%3BDavis%2C+Scott&rft.aulast=Hartge&rft.aufirst=Patricia&rft.date=2005-04-01&rft.volume=14&rft.issue=4&rft.spage=934&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.issn=10559965&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 - Herbicides; Lymphoma; Dust; Vacuum; Carpets; Risk assessment; biomarkers ER - TY - JOUR T1 - Models of Phase 1 vaccine trials: optimization of trial design to minimize risks of multiple serious adverse events AN - 17493098; 6242357 AB - A mathematical model of Phase 1 vaccine trial design was used to investigate strategies for minimizing the number of serious adverse events (SAEs) that could be encountered in the first Phase 1 trials of new vaccine formulations. For a relatively standard dose escalation trial with three dose groups each with 10 subjects, an optimal balanced between risk of more than one serious adverse event and trial design is achieved by splitting each dose group into two subgroups of three and seven. Based on the modeling, for a two vaccination, dose-escalating Phase 1 trial, a design where all subjects receive the first vaccination before any subject receives a second vaccination generally carries a lower risk of multiple serious adverse events than other designs. JF - Vaccine AU - Saul, A AD - Malaria Vaccine Development Branch/NIAID/NIH, 5460 Fishers Lane, Room 1113, Twinbrook I, Rockville, MD 20852, USA, asaul@niaid.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 3068 EP - 3075 PB - Butterworth-Heinemann, 313 Washington St. Newton MA 02158 USA VL - 23 IS - 23 SN - 0264-410X, 0264-410X KW - Health & Safety Science Abstracts; Risk Abstracts; Immunology Abstracts KW - Mathematical models KW - Risk reduction KW - Vaccination KW - Clinical trials KW - Vaccines KW - Side effects KW - F 06100:Vaccines - active immunity KW - R2 23060:Medical and environmental health KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17493098?accountid=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=Vaccine&rft.atitle=Models+of+Phase+1+vaccine+trials%3A+optimization+of+trial+design+to+minimize+risks+of+multiple+serious+adverse+events&rft.au=Saul%2C+A&rft.aulast=Saul&rft.aufirst=A&rft.date=2005-04-01&rft.volume=23&rft.issue=23&rft.spage=3068&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2Fj.vaccine.2004.10.048 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Side effects; Risk reduction; Vaccines; Clinical trials; Vaccination; Mathematical models DO - http://dx.doi.org/10.1016/j.vaccine.2004.10.048 ER - TY - JOUR T1 - Increased Immunogenicity of an Anchor-Modified Tumor-Associated Antigen Is Due to the Enhanced Stability of the Peptide/MHC Complex: Implications for Vaccine Design AN - 17492843; 6267168 AB - The use of "anchor-fixed" altered peptide ligands is of considerable interest in the development of therapeutic vaccines for cancer and infectious diseases, but the mechanism by which successful altered peptide ligands elicit enhanced immunity is unclear. In this study, we have determined the crystallographic structure of a major tumor rejection Ag, gp100 sub(209-217), in complex with the HLA-A*0201 (HLA-A2) molecule, as well as the structure of a modified version of the peptide which substitutes methionine for threonine at position 2 (T2M; gp100 sub(209-2M)). The T2M-modified peptide, which is more immunogenic in vitro and in vivo, binds HLA-A2 with a similar to 9-fold greater affinity and has a similar to 7-fold slower dissociation rate at physiological temperature. Within the limit of the crystallographic data, the T2M substitution does not alter the structure of the peptide/HLA-A2 complex. Consistent with this finding, in peripheral blood from 95 human subjects, we were unable to identify higher frequencies of T cells specific for either the native or modified peptide. These data strongly support the conclusion that the greater immunogenicity of the gp100 sub(209-2M) peptide is due to the enhanced stability of the peptide/MHC complex, validating the anchor-fixing approach for generating therapeutic vaccine candidates. Thermodynamic data suggest that the enhanced stability of the T2M-modified peptide/HLA-A2 complex is attributable to the increased hydrophobicity of the modified peptide, but the gain due to hydrophobicity is offset considerably by the loss of a hydrogen bond made by the native peptide to the HLA-A2 molecule. Our findings have broad implications for the optimization of current vaccine-design strategies. JF - Journal of Immunology AU - Borbulevych, Oleg Y AU - Baxter, Tiffany K AU - Yu, Zhiya AU - Restifo, Nicholas P AU - Baker, Brian M AD - Department of Chemistry and Biochemistry and. Walther Cancer Research Center, University of Notre Dame, Notre Dame, IN 46556. National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 4812 EP - 4820 PB - American Association of Immunologists, 9650 Rockville Pike Bethesda MD 20814-3998 USA, [URL:http://www.jimmunol.org/] VL - 174 IS - 8 SN - 0022-1767, 0022-1767 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Temperature effects KW - Histocompatibility antigen HLA KW - Gene polymorphism KW - Major histocompatibility complex KW - Peripheral blood KW - Hydrophobicity KW - Infectious diseases KW - Hydrogen bonding KW - Immunogenicity KW - Antigen (tumor-associated) KW - Vaccines KW - W3 33365:Vaccines (other) KW - F 06150:Immunotherapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17492843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+Immunogenicity+of+an+Anchor-Modified+Tumor-Associated+Antigen+Is+Due+to+the+Enhanced+Stability+of+the+Peptide%2FMHC+Complex%3A+Implications+for+Vaccine+Design&rft.au=Borbulevych%2C+Oleg+Y%3BBaxter%2C+Tiffany+K%3BYu%2C+Zhiya%3BRestifo%2C+Nicholas+P%3BBaker%2C+Brian+M&rft.aulast=Borbulevych&rft.aufirst=Oleg&rft.date=2005-04-01&rft.volume=174&rft.issue=8&rft.spage=4812&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Histocompatibility antigen HLA; Vaccines; Hydrophobicity; Immunogenicity; Major histocompatibility complex; Hydrogen bonding; Antigen (tumor-associated); Gene polymorphism; Temperature effects; Peripheral blood; Infectious diseases ER - TY - JOUR T1 - A human phase 1 vaccine clinical trial of the Plasmodium falciparum malaria vaccine candidate apical membrane antigen 1 in Montanide ISA720 adjuvant AN - 17491489; 6242350 AB - A dose escalating, placebo-controlled phase 1 trial was conducted to test the safety and immunogenicity of a vaccine containing recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) formulated in Montanide ISA720. Three groups of volunteers were vaccinated intramuscularly with 5 mu g, 20 mu g or 80 mu g of AMA1, respectively, in 0.5 mL of formulation at 0, 3 and 6 months. Anti-AMA1 antibody levels and T cell stimulation indices were measured before and after each vaccination. No vaccine-related serious adverse events were recorded. Most subjects generated a mild to moderate, transient local reaction after the first vaccination. Three subjects developed a local reaction approximately 10 days following vaccination. Six of the 29 subjects seroconverted. Only one of these developed a high antibody titre. However, the interpretation of this trial was compromised by a loss of potency of the formulated vaccine during the course of the study. JF - Vaccine AU - Saul, A AU - Lawrence, G AU - Allworth, A AU - Elliott, S AU - Anderson, K AU - Rzepczyk, C AU - Martin, L B AU - Taylor, D AU - Eisen, D P AU - Irving, DO AU - Pye, D AU - Crewther, P E AU - Hodder, AN AU - Murphy, V J AU - Anders, R F AD - The Cooperative Research Centre for Vaccine Technology, Brisbane, Qld, Australia, asaul@niaid.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 3076 EP - 3083 PB - Butterworth-Heinemann, 313 Washington St. Newton MA 02158 USA VL - 23 IS - 23 SN - 0264-410X, 0264-410X KW - Biotechnology and Bioengineering Abstracts; Health & Safety Science Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Apical membrane antigen 1 KW - vaccines KW - Malaria KW - Adjuvants KW - clinical trials KW - Clinical trials KW - Lymphocytes T KW - Plasmodium falciparum KW - Vaccination KW - Antibodies KW - Immunogenicity KW - K 03086:Immunology & vaccination KW - W3 33365:Vaccines (other) KW - F 06100:Vaccines - active immunity KW - W 30965:Miscellaneous, Reviews KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17491489?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+human+phase+1+vaccine+clinical+trial+of+the+Plasmodium+falciparum+malaria+vaccine+candidate+apical+membrane+antigen+1+in+Montanide+ISA720+adjuvant&rft.au=Saul%2C+A%3BLawrence%2C+G%3BAllworth%2C+A%3BElliott%2C+S%3BAnderson%2C+K%3BRzepczyk%2C+C%3BMartin%2C+L+B%3BTaylor%2C+D%3BEisen%2C+D+P%3BIrving%2C+DO%3BPye%2C+D%3BCrewther%2C+P+E%3BHodder%2C+AN%3BMurphy%2C+V+J%3BAnders%2C+R+F&rft.aulast=Saul&rft.aufirst=A&rft.date=2005-04-01&rft.volume=23&rft.issue=23&rft.spage=3076&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2Fj.vaccine.2004.09.040 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Plasmodium falciparum; vaccines; clinical trials; Vaccination; Clinical trials; Antibodies; Apical membrane antigen 1; Malaria; Lymphocytes T; Immunogenicity; Adjuvants DO - http://dx.doi.org/10.1016/j.vaccine.2004.09.040 ER - TY - JOUR T1 - Male Breast Cancer Incidence Among Atomic Bomb Survivors AN - 17482771; 6246118 AB - To learn more about the role of ionizing radiation in the development of male breast cancer, we evaluated male breast cancer incidence among 45 880 male members of the Life Span Study cohort of Japanese atomic bomb survivors. Male breast cancers, diagnosed between January 1, 1958, and December 31, 1998, were identified through the Hiroshima and Nagasaki Tumor Registries. Nine male breast cancers were diagnosed among exposed Life Span Study members (crude rate = 1.8 per 100 000 person-years), and three were diagnosed among nonexposed cohort members (crude rate = 0.5 per 100 000 person-years). A statistically significant dose-response relation was observed (excess relative risk per sievert = 8, 95% confidence interval = 0.8 to 48; P = .01). Our finding of a statistically significant association between ionizing radiation and male breast cancer incidence adds to the very limited information that shows an association between radiation exposure and an increased risk of male breast cancer. JF - Journal of the National Cancer Institute AU - Ron, Elaine AU - Ikeda, Takayoshi AU - Preston, Dale L AU - Tokuoka, Shoji AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NationalInstitute of Health, Department of Health andHuman Services, Bethesda, MD Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 603 EP - 605 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 97 IS - 8 SN - 0027-8874, 0027-8874 KW - Risk Abstracts; Health & Safety Science Abstracts KW - Atomic bombs KW - males KW - Japan, Nagasaki KW - Dose-response effects KW - Ionizing radiation KW - Breast cancer KW - H 8000:Radiation Safety/Electrical Safety KW - R2 23020:Technological risks UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17482771?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Male+Breast+Cancer+Incidence+Among+Atomic+Bomb+Survivors&rft.au=Ron%2C+Elaine%3BIkeda%2C+Takayoshi%3BPreston%2C+Dale+L%3BTokuoka%2C+Shoji&rft.aulast=Ron&rft.aufirst=Elaine&rft.date=2005-04-01&rft.volume=97&rft.issue=8&rft.spage=603&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Japan, Nagasaki; Breast cancer; Ionizing radiation; Atomic bombs; Dose-response effects; males ER - TY - JOUR T1 - Nicotine induces conditioned place preferences over a large range of doses in rats AN - 17395037; 6484030 AB - Rationale: Conditioned place preference (CPP) procedures provide one measure of potential rewarding effects of abused drugs. Many attempts to induce CPP with nicotine have been unsuccessful. Objectives: To assess the influence of nicotine dose and stimulus assignment procedure on development of nicotine-induced CPP. Methods: Initial preferences for one side of a two-compartment apparatus were first determined in Sprague-Dawley rats. In subsequent conditioning trials, the compartment paired with nicotine was the initially preferred side for half of the rats, and the initially non-preferred side for the other half. Rats received either an injection of nicotine (0.01-2 mg/kg SC) before being placed in one compartment (three trials) or saline before being placed in the other compartment (three trials). Control rats had saline injections associated with both compartments. A final test trial with no injection assessed final place preference. Results: Significant CPP were induced by 0.1-1.4 mg/kg doses of nicotine. Nicotine-induced CPP were only apparent when nicotine was paired with the initially non-preferred side. Moreover, a very high dose of nicotine (2 mg/kg) induced conditioned place aversion when paired with the initially preferred side of the apparatus. Conclusions: Nicotine induced significant CPP across a wide range of doses, in accordance with its role as the primary addictive component of tobacco. Small preferences for one side of the apparatus played a major role in the development of nicotine-induced CPP. These findings suggest that biased procedures may be more suitable than unbiased procedures for evaluation of rewarding effects of nicotine using CPP paradigms. JF - Psychopharmacology AU - Le Foll, Bernard AU - Goldberg, Steven R AD - Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, blefoll@intra.nida.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 481 EP - 492 PB - Springer-Verlag (Berlin), Heidelberger Platz 3 Berlin 14197 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 178 IS - 4 SN - 0033-3158, 0033-3158 KW - CSA Neurosciences Abstracts; Animal Behavior Abstracts; Toxicology Abstracts KW - Place preferences KW - Dose dependency KW - Nicotine KW - Aversion KW - Reinforcement KW - Tobacco KW - Drug abuse KW - N3 11047:Neuropsychobiology KW - X 24180:Social poisons & drug abuse KW - Y 25817:Mammals (excluding primates) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17395037?accountid=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+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Adoptive+cell+transfer+therapy+following+non-myeloablative+but+lymphodepleting+chemotherapy+for+the+treatment+of+patients+with+refractory+metastatic+melanoma.&rft.au=Dudley%2C+Mark+E%3BWunderlich%2C+John+R%3BYang%2C+James+C%3BSherry%2C+Richard+M%3BTopalian%2C+Suzanne+L%3BRestifo%2C+Nicholas+P%3BRoyal%2C+Richard+E%3BKammula%2C+Udai%3BWhite%2C+Don+E%3BMavroukakis%2C+Sharon+A%3BRogers%2C+Linda+J%3BGracia%2C+Gerald+J%3BJones%2C+Stephanie+A%3BMangiameli%2C+David+P%3BPelletier%2C+Michelle+M%3BGea-Banacloche%2C+Juan%3BRobinson%2C+Michael+R%3BBerman%2C+David+M%3BFilie%2C+Armando+C%3BAbati%2C+Andrea%3BRosenberg%2C+Steven+A&rft.aulast=Dudley&rft.aufirst=Mark&rft.date=2005-04-01&rft.volume=23&rft.issue=10&rft.spage=2346&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 revised - 2006-01-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Dose dependency; Place preferences; Nicotine; Aversion; Tobacco; Reinforcement; Drug abuse DO - http://dx.doi.org/10.1007/s00213-004-2021-5 ER - TY - JOUR T1 - Modeling a description logic vocabulary for cancer research AN - 17367073; 6444901 AB - The National Cancer Institute has developed the NCI Thesaurus, a biomedical vocabulary for cancer research, covering terminology across a wide range of cancer research domains. A major design goal of the NCI Thesaurus is to facilitate translational research. We describe: the features of Ontylog, a description logic used to build NCI Thesaurus; our methodology for enhancing the terminology through collaboration between ontologists and domain experts, and for addressing certain real world challenges arising in modeling the Thesaurus; and finally, we describe the conversion of NCI Thesaurus from Ontylog into Web Ontology Language Lite. Ontylog has proven well suited for constructing big biomedical vocabularies. We have capitalized on the Ontylog constructs Kind and Role in the collaboration process described in this paper to facilitate communication between ontologists and domain experts. The artifacts and processes developed by NCI for collaboration may be useful in other biomedical terminology development efforts. JF - Journal of Biomedical Informatics AU - Hartel, F W AU - De Coronado, S AU - Dionne, R AU - Fragoso, G AU - Golbeck, J AD - National Cancer Institute Center for Bioinformatics, 6116 Executive Blvd, Suite 403, Bethesda, MD 20892-8335, United States, decorons@mail.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 114 EP - 129 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 38 IS - 2 SN - 1532-0464, 1532-0464 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Translation KW - Communication KW - Language KW - Bioinformatics 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/17367073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modeling+a+description+logic+vocabulary+for+cancer+research&rft.au=Hartel%2C+F+W%3BDe+Coronado%2C+S%3BDionne%2C+R%3BFragoso%2C+G%3BGolbeck%2C+J&rft.aulast=Hartel&rft.aufirst=F&rft.date=2005-04-01&rft.volume=38&rft.issue=2&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomedical+Informatics&rft.issn=15320464&rft_id=info:doi/10.1016%2Fj.jbi.2004.09.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Language; Translation; Communication; Bioinformatics DO - http://dx.doi.org/10.1016/j.jbi.2004.09.001 ER - TY - JOUR T1 - Initial Ocular Following in Humans Depends Critically on the Fourier Components of the Motion Stimulus AN - 1677950656; 19284763 AB - Abstract: Visual motion is sensed by low-level (energy-based) and high-level (feature-based) mechanisms. Our interest is in the motion detectors underlying the initial ocular following responses (OFR) that are elicited at ultrashort latencies by sudden motions of large images. OFR were elicited in humans by applying horizontal motion to vertical square-wave gratings lacking the fundamental. In the frequency domain, a pure square wave is composed of the odd harmonics-first, third, fifth, seventh, etc.-such that the third, fifth, seventh, etc., have amplitudes that are one-third, one-fifth, one-seventh, etc., that of the first, and the missing fundamental stimulus lacks the first harmonic. Motion consisted of successive quarter-wavelength steps, so the features and 4n+1 harmonics (where n= integer) shifted forward, whereas the 4n-1 harmonics-including the strongest Fourier component (the third harmonic)-shifted backward (spatial aliasing). Thus, the net Fourier energy and the non-Fourier features moved in opposite directions. Initial OFR, recorded with the search coil technique, had minimum latencies of 60 to 70 ms and were always in the direction of the third harmonic, for example, leftward steps resulted in rightward OFR. Thus, the earliest OFR were strongly dependent on the motion of the major Fourier component, consistent with mediation by oriented spatiotemporal visual filters as in the well-known energy model of motion detection. Introducing interstimulus intervals of 10 to 100 ms (during which the screen was uniform gray) reversed the initial direction of tracking, consistent with extensive neurophysiological and psychophysical data suggesting that the visual input to the motion detectors has a biphasic temporal impulse response. JF - Annals of the New York Academy of Sciences AU - Chen, K J AU - Sheliga, B M AU - Fitzgibbon, E J AU - Miles, F A AD - Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-4435, USA Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 260 EP - 271 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 1039 IS - 1 SN - 0077-8923, 0077-8923 KW - Solid State and Superconductivity Abstracts (SO); Environmental Engineering Abstracts (EN); Electronics and Communications Abstracts (EA) KW - Harmonics KW - Frequency domains KW - Human KW - Fourier analysis KW - Detectors KW - Image detection KW - Searching KW - Visual UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1677950656?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvironmentalengabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Initial+Ocular+Following+in+Humans+Depends+Critically+on+the+Fourier+Components+of+the+Motion+Stimulus&rft.au=Chen%2C+K+J%3BSheliga%2C+B+M%3BFitzgibbon%2C+E+J%3BMiles%2C+F+A&rft.aulast=Chen&rft.aufirst=K&rft.date=2005-04-01&rft.volume=1039&rft.issue=1&rft.spage=260&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1196%2Fannals.1325.025 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-04-01 N1 - Document feature - figure 5 N1 - Last updated - 2015-05-04 DO - http://dx.doi.org/10.1196/annals.1325.025 ER - TY - JOUR T1 - Cancer risk associated with receipt of vaccines contaminated with simian virus 40: epidemiologic research AN - 1028021801; 16614491 AB - Simian virus (SV)40 was an accidental contaminant of poliovirus vaccines used widely in the USA and other countries in 1955-1962. Exposure to SV40 via contaminated vaccines has led to concern as SV40 causes cancer in laboratory animals. In addition, some laboratories, although not all, have detected SV40 DNA in human tumors including mesothelioma, certain brain tumors, osteosarcoma and non-Hodgkin''s lymphoma. This article reviews the data regarding contamination of poliovirus vaccines with SV40 and summarizes the results from epidemiologic studies of vaccine recipients. Long-term follow-up studies have not revealed recipients of SV40-contaminated poliovirus vaccines to be at an increased risk for cancer. Thus, these studies are somewhat reassuring and indicate that either SV40 does not readily infect humans or, following infection, does not cause cancer. Recognizing that the history of SV40 contamination of vaccines highlights an inherent risk of contamination of vaccines with adventitious agents, the Institute of Medicine recently called for the development of a comprehensive US plan to prevent vaccine contamination and respond to potential contamination events when they arise. JF - Expert Review of Vaccines AU - Engels, Eric A AD - National Cancer InstituteViral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, DHHS, 6120 Executive Blvd, EPS 8010Rockville, MD 20892USA, engelse@exchange.nih.gov Y1 - 2005/04// PY - 2005 DA - Apr 2005 SP - 197 EP - 206 PB - Future Science Group (FSG), Unitec House, 2 Albert Place London N3 1QB United Kingdom VL - 4 IS - 2 SN - 1476-0584, 1476-0584 KW - Virology & AIDS Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - Brain tumors KW - Cancer KW - Contaminants KW - Contamination KW - DNA KW - Data processing KW - Historical account KW - Infection KW - Laboratory animals KW - Lymphoma KW - Osteosarcoma KW - Poliovirus KW - Reviews KW - Risk factors KW - Tumors KW - Vaccines KW - mesothelioma KW - vaccines KW - Simian virus 40 KW - USA KW - R2 23060:Medical and environmental health KW - H 4000:Food and Drugs KW - V 22370:Oncology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1028021801?accountid=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+Immunology&rft.atitle=Maintenance+of+Pulmonary+Th1+Effector+Function+in+Chronic+Tuberculosis+Requires+Persistent+IL-12+Production&rft.au=Feng%2C+Carl+G%3BJankovic%2C+Dragana%3BKullberg%2C+Marika%3BCheever%2C+Allen%3BScanga%2C+Charles+A%3BHieny%2C+Sara%3BCaspar%2C+Patricia%3BYap%2C+George+S%3BSher%2C+Alan&rft.aulast=Feng&rft.aufirst=Carl&rft.date=2005-04-01&rft.volume=174&rft.issue=7&rft.spage=4185&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 - 2012-07-01 N1 - Number of references - 55 N1 - Last updated - 2013-01-11 N1 - SubjectsTermNotLitGenreText - Data processing; Contamination; Laboratory animals; Osteosarcoma; Infection; Cancer; Brain tumors; Reviews; Risk factors; DNA; mesothelioma; Vaccines; Contaminants; Lymphoma; Historical account; Poliovirus; vaccines; Tumors; Simian virus 40; USA DO - http://dx.doi.org/10.1586/14760584.4.2.197 ER - TY - JOUR T1 - Solution Structure of Enzyme IIA super(Chitobiose) from the N,N'-Diacetylchitobiose Branch of the Escherichia coli Phosphotransferase System AN - 17482529; 6189660 AB - The solution structure of trimeric Escherichia coli enzyme IIA super(Chb) (34 kDa), a component of the N,N'-diacetylchitobiose/lactose branch of the phosphotransferase signal transduction system, has been determined by NMR spectroscopy. Backbone residual dipolar couplings were used to provide long range orientational restraints, and long range (|i -j| => 5 residues) nuclear Overhauser enhancement restraints were derived exclusively from samples in which at least one subunit was super(15)N/ super(13)C/ super(2)H/(Val-Leu-Ile)-methyl-protonated. Each subunit consists of a three-helix bundle. Hydrophobic residues lining helix 3 of each subunit are largely responsible for the formation of a parallel coiled-coil trimer. The active site histidines (His-89 from each subunit) are located in three symmetrically placed deep crevices located at the interface of two adjacent subunits (A and C, C and B, and B and A). Partially shielded from bulk solvent, structural modeling suggests that phosphorylated His-89 is stabilized by electrostatic interactions with the side chains of His-93 from the same subunit and Gln-91 from the adjacent subunit. Comparison with the x-ray structure of Lactobacillus lactis IIA super(Lac) reveals some substantial structural differences, particularly in regard to helix 3, which exhibits a 40 degree kink in IIA super(Lac) versus a 7 degree bend in IIA super(Chb). This is associated with the presence of an unusually large (230-Aa super(3)) buried hydrophobic cavity at the trimer interface in IIA super(Lac) that is reduced to only 45 Aa super(3) in IIA super(Chb). JF - Journal of Biological Chemistry AU - Tang, Chun AU - Williams, David C AU - Ghirlando, Rodolfo AU - Clore, GMarius AD - Laboratories of Chemical Physics and Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland Y1 - 2005/03/25/ PY - 2005 DA - 2005 Mar 25 SP - 11770 EP - 11780 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 - 280 IS - 12 SN - 0021-9258, 0021-9258 KW - chitobiose KW - N,N'-diacetylchitobiose KW - Microbiology Abstracts B: Bacteriology KW - Lactose KW - Magnetic resonance spectroscopy KW - Histidine KW - Lactobacillus lactis KW - Escherichia coli KW - Hydrophobicity KW - phosphotransferase KW - Signal transduction KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17482529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Enzyme+IIA+super%28Chitobiose%29+from+the+N%2CN%27-Diacetylchitobiose+Branch+of+the+Escherichia+coli+Phosphotransferase+System&rft.au=Tang%2C+Chun%3BWilliams%2C+David+C%3BGhirlando%2C+Rodolfo%3BClore%2C+GMarius&rft.aulast=Tang&rft.aufirst=Chun&rft.date=2005-03-25&rft.volume=280&rft.issue=12&rft.spage=11770&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Lactobacillus lactis; Hydrophobicity; phosphotransferase; Histidine; Magnetic resonance spectroscopy; Signal transduction; Lactose ER - TY - JOUR T1 - Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage. AN - 67539289; 15784871 AB - Delayed cerebral vasospasm causes permanent neurological deficits or death in at least 15% of patients following otherwise successful treatment for ruptured intracranial aneurysm. Decreased bioavailability of nitric oxide has been associated with the development of cerebral vasospasm. To determine whether infusions of nitrite will prevent delayed cerebral vasospasm. A total of 14 anesthetized cynomolgus monkeys had an autologous blood clot placed around the right middle cerebral artery. Cerebral arteriography was performed before clot placement and on days 7 and 14 to assess vasospasm. The study was conducted from August 2003 to February 2004. A 90-mg sodium nitrite intravenous solution infused over 24 hours plus a 45-mg sodium nitrite bolus daily (n = 3); a 180-mg sodium nitrite intravenous solution infused over 24 hours (n = 3); or a control saline solution infusion (n = 8). Each was infused continuously for 14 days. Nitrite, S-nitrosothiol, and methemoglobin levels in blood and cerebrospinal fluid and degree of arteriographic vasospasm. In control monkeys, mean (SD) cerebrospinal fluid nitrite levels decreased from 3.1 (1.5) micromol/L to 0.4 (0.1) micromol/L at day 7 and to 0.4 (0.4) micromol/L at day 14 (P = .03). All 8 control monkeys developed significant vasospasm of the right middle cerebral artery, which was complicated by stroke and death in 1 animal. Sodium nitrite infusions increased the nitrite and methemoglobin levels (<2.1% of total hemoglobin) in the blood and cerebrospinal fluid without evoking systemic hypotension. Nitrite infusion prevented development of vasospasm (no animals developed significant vasospasm; mean [SD] reduction in right middle cerebral artery area on day 7 after subarachnoid hemorrhage of 8% [9%] in nitrite-treated monkeys vs 47% [5%] in saline-treated controls; P<.001). There was a negative correlation between the concentration of nitrite in cerebrospinal fluid and the degree of cerebral vasospasm (P<.001). Pharmacological effects of nitrite infusion were also associated with the formation of S-nitrosothiol in cerebrospinal fluid. There was no clinical or pathological evidence of nitrite toxicity. Subacute sodium nitrite infusions prevented delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage. JF - JAMA AU - Pluta, Ryszard M AU - Dejam, Andre AU - Grimes, George AU - Gladwin, Mark T AU - Oldfield, Edward H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md 20892, USA. rysiek@ninds.nih.gov Y1 - 2005/03/23/ PY - 2005 DA - 2005 Mar 23 SP - 1477 EP - 1484 VL - 293 IS - 12 KW - Nitrites KW - 0 KW - S-Nitrosothiols KW - Methemoglobin KW - 9008-37-1 KW - Sodium Nitrite KW - M0KG633D4F KW - Abridged Index Medicus KW - Index Medicus KW - Nitrites -- blood KW - Animals KW - Cerebral Angiography KW - Macaca fascicularis KW - Infusions, Intravenous KW - Infarction, Middle Cerebral Artery KW - Nitrites -- cerebrospinal fluid KW - Disease Models, Animal KW - S-Nitrosothiols -- cerebrospinal fluid KW - S-Nitrosothiols -- blood KW - Methemoglobin -- analysis KW - Sodium Nitrite -- administration & dosage KW - Vasospasm, Intracranial -- prevention & control KW - Vasospasm, Intracranial -- diagnostic imaging KW - Sodium Nitrite -- therapeutic use KW - Vasospasm, Intracranial -- metabolism KW - Vasospasm, Intracranial -- etiology KW - Subarachnoid Hemorrhage -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67539289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nitrite+infusions+to+prevent+delayed+cerebral+vasospasm+in+a+primate+model+of+subarachnoid+hemorrhage.&rft.au=Pluta%2C+Ryszard+M%3BDejam%2C+Andre%3BGrimes%2C+George%3BGladwin%2C+Mark+T%3BOldfield%2C+Edward+H&rft.aulast=Pluta&rft.aufirst=Ryszard&rft.date=2005-03-23&rft.volume=293&rft.issue=12&rft.spage=1477&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 - 2005-03-29 N1 - Date created - 2005-03-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 2005 Jul 6;294(1):40; author reply 40-1 [15998885] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intramolecular interaction between phosphorylated tyrosine-783 and the C-terminal Src homology 2 domain activates phospholipase C-gamma1. AN - 67546745; 15764700 AB - Phospholipase C-gamma1 (PLC-gamma1) contains two tandem Src homology 2 (SH2) domains. The NH(2)-terminal SH2 domain has been known to mediate the binding of PLC-gamma1 to receptor protein tyrosine kinases, which then activate PLC-gamma1 via phosphorylation at Y783. We now show that the phosphorylated Y783 residue (pY783) associates with the COOH-terminal SH2 domain [SH2(C)] within the same molecule of PLC-gamma1. The specificity of this intramolecular interaction is demonstrated in several ways. The mutation of SH2(C), but not of the NH(2)-terminal SH2 domain, exposes pY783 and makes it available for binding by anti-pY783 antibodies, for intermolecular association with a GST fusion protein containing the tandem SH2 domains of PLC-gamma1 and for dephosphorylation by phosphatases. The intramolecular interaction between pY783 and SH2(C) induces a rearrangement of surface charge such that PLC-gamma1 molecules phosphorylated at Y783 are retained more strongly by heparin resins than are unphosphorylated molecules. Finally, the intramolecular interaction of pY783 with SH2(C) results in activation of phospholipase activity. Our results thus clarify the molecular mechanism of PLC-gamma1 activation, revealing the specific function of pY783 and the distinct roles of the two SH2 domains in this process. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Poulin, Benoit AU - Sekiya, Fujio AU - Rhee, Sue Goo AD - Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8015, USA. Y1 - 2005/03/22/ PY - 2005 DA - 2005 Mar 22 SP - 4276 EP - 4281 VL - 102 IS - 12 SN - 0027-8424, 0027-8424 KW - Recombinant Proteins KW - 0 KW - Tyrosine KW - 42HK56048U KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phospholipase C gamma KW - EC 3.1.4.3 KW - Index Medicus KW - Animals KW - Enzyme Activation KW - Recombinant Proteins -- genetics KW - Models, Biological KW - src Homology Domains KW - Binding Sites KW - Tyrosine -- chemistry KW - Mutagenesis, Site-Directed KW - Rats KW - Phosphorylation KW - Recombinant Proteins -- metabolism KW - In Vitro Techniques KW - Recombinant Proteins -- chemistry KW - Protein Conformation KW - Type C Phospholipases -- chemistry KW - Type C Phospholipases -- genetics KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67546745?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Intramolecular+interaction+between+phosphorylated+tyrosine-783+and+the+C-terminal+Src+homology+2+domain+activates+phospholipase+C-gamma1.&rft.au=Poulin%2C+Benoit%3BSekiya%2C+Fujio%3BRhee%2C+Sue+Goo&rft.aulast=Poulin&rft.aufirst=Benoit&rft.date=2005-03-22&rft.volume=102&rft.issue=12&rft.spage=4276&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 - 2005-05-03 N1 - Date created - 2005-03-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1999 Sep 10;274(37):26091-7 [10473558] J Immunol. 1999 Aug 15;163(4):1746-9 [10438904] Exp Cell Res. 1999 Nov 25;253(1):15-24 [10579907] J Biol Chem. 2000 Mar 3;275(9):6411-6 [10692443] Annu Rev Biochem. 2001;70:281-312 [11395409] Development. 2002 Aug;129(15):3533-44 [12117804] J Biol Chem. 2004 Jul 30;279(31):32181-90 [15161916] Mol Cell Biol. 2004 Nov;24(22):9986-99 [15509800] Mol Cell Biol. 1985 Dec;5(12):3403-9 [3939316] J Biol Chem. 1988 Oct 5;263(28):14497-504 [2459119] J Biol Chem. 1990 Mar 5;265(7):3940-3 [1689310] J Biol Chem. 1990 Mar 5;265(7):3944-8 [1689311] Science. 1990 Nov 30;250(4985):1253-6 [1700866] Cell. 1991 May 3;65(3):435-41 [1708307] J Biol Chem. 1992 May 15;267(14):9678-83 [1315766] J Biol Chem. 1992 May 25;267(15):10447-56 [1316902] J Biol Chem. 1992 Aug 15;267(23):16048-55 [1644792] Cell. 1994 May 6;77(3):461-72 [8181064] Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):2999-3003 [9096335] J Biol Chem. 1998 Jan 9;273(2):729-35 [9422724] EMBO J. 1998 Jan 15;17(2):414-22 [9430633] J Biol Chem. 1998 Feb 20;273(8):4465-9 [9468499] J Immunol. 1998 Feb 1;160(3):1059-66 [9570517] Mol Cell Biol. 1999 Jul;19(7):4961-70 [10373546] Mol Cell Biol. 1999 Nov;19(11):7388-98 [10523627] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HIF-1alpha induces genetic instability by transcriptionally downregulating MutSalpha expression. AN - 67533941; 15780936 AB - Hypoxia promotes genetic instability by undefined mechanisms. The transcription factor HIF-1alpha is crucial for the cellular response to hypoxia and is frequently overexpressed in human cancers, resulting in the activation of genes essential for cell survival. Here, we demonstrate that HIF-1alpha is responsible for genetic instability at the nucleotide level by inhibiting MSH2 and MSH6, thereby decreasing levels of the MSH2-MSH6 complex, MutSalpha, which recognizes base mismatches. HIF-1alpha displaces the transcriptional activator Myc from Sp1 binding to repress MutSalpha expression in a p53-dependent manner; Sp1 serves as a molecular switch by recruiting HIF-1alpha to the gene promoter under hypoxia. Furthermore, in human sporadic colon cancers, HIF-1alpha overexpression is statistically associated with the loss of MSH2 expression, especially when p53 is immunochemically undetectable. These findings indicate that the regulation of DNA repair is an integral part of the hypoxic response, providing molecular insights into the mechanisms underlying hypoxia-induced genetic instability. JF - Molecular cell AU - Koshiji, Minori AU - To, Kenneth K-W AU - Hammer, Stefanie AU - Kumamoto, Kensuke AU - Harris, Adrian L AU - Modrich, Paul AU - Huang, L Eric AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2005/03/18/ PY - 2005 DA - 2005 Mar 18 SP - 793 EP - 803 VL - 17 IS - 6 SN - 1097-2765, 1097-2765 KW - DNA-Binding Proteins KW - 0 KW - G-T mismatch-binding protein KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - MYC protein, human KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-myc KW - Sp1 Transcription Factor KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - MSH2 protein, human KW - EC 3.6.1.3 KW - MutS Homolog 2 Protein KW - Index Medicus KW - Sp1 Transcription Factor -- genetics KW - Colonic Neoplasms -- genetics KW - DNA Repair KW - Humans KW - Proto-Oncogene Proteins c-myc -- genetics KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Protein Binding KW - Tumor Cells, Cultured KW - Down-Regulation KW - Sp1 Transcription Factor -- metabolism KW - Colonic Neoplasms -- metabolism KW - Colonic Neoplasms -- pathology KW - Transcription Factors -- metabolism KW - Chromosomal Instability KW - Proto-Oncogene Proteins -- metabolism KW - DNA-Binding Proteins -- genetics KW - Transcription, Genetic KW - Promoter Regions, Genetic -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Cell Hypoxia KW - Transcription Factors -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67533941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=HIF-1alpha+induces+genetic+instability+by+transcriptionally+downregulating+MutSalpha+expression.&rft.au=Koshiji%2C+Minori%3BTo%2C+Kenneth+K-W%3BHammer%2C+Stefanie%3BKumamoto%2C+Kensuke%3BHarris%2C+Adrian+L%3BModrich%2C+Paul%3BHuang%2C+L+Eric&rft.aulast=Koshiji&rft.aufirst=Minori&rft.date=2005-03-18&rft.volume=17&rft.issue=6&rft.spage=793&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 - 2005-04-26 N1 - Date created - 2005-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer. An anchor for tumor cell invasion. AN - 67523054; 15774745 JF - Science (New York, N.Y.) AU - Yuspa, Stuart H AU - Epstein, Ervin H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. sy12j@nih.gov Y1 - 2005/03/18/ PY - 2005 DA - 2005 Mar 18 SP - 1727 EP - 1728 VL - 307 IS - 5716 KW - Cell Adhesion Molecules KW - 0 KW - Collagen Type VII KW - I-kappa B Proteins KW - NFKBIA protein, human KW - Nfkbia protein, mouse KW - Transforming Growth Factor beta KW - kalinin KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - Index Medicus KW - Animals KW - Neoplasm Invasiveness KW - Disease Susceptibility KW - Humans KW - I-kappa B Proteins -- metabolism KW - Transduction, Genetic KW - Mice KW - Genes, ras KW - Cell Adhesion Molecules -- metabolism KW - I-kappa B Proteins -- genetics KW - Protein Structure, Tertiary KW - Transforming Growth Factor beta -- metabolism KW - Mutation KW - Cell Transformation, Neoplastic KW - Epidermolysis Bullosa Dystrophica -- metabolism KW - Carcinoma, Squamous Cell -- etiology KW - Collagen Type VII -- chemistry KW - Skin Neoplasms -- etiology KW - Skin Neoplasms -- pathology KW - Collagen Type VII -- genetics KW - Epidermolysis Bullosa Dystrophica -- complications KW - Epidermolysis Bullosa Dystrophica -- pathology KW - Skin Neoplasms -- genetics KW - Skin Neoplasms -- physiopathology KW - Epidermolysis Bullosa Dystrophica -- genetics KW - Carcinoma, Squamous Cell -- pathology KW - Carcinoma, Squamous Cell -- physiopathology KW - Carcinoma, Squamous Cell -- genetics KW - Keratinocytes -- pathology KW - Keratinocytes -- metabolism KW - Collagen Type VII -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67523054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cancer.+An+anchor+for+tumor+cell+invasion.&rft.au=Yuspa%2C+Stuart+H%3BEpstein%2C+Ervin+H&rft.aulast=Yuspa&rft.aufirst=Stuart&rft.date=2005-03-18&rft.volume=307&rft.issue=5716&rft.spage=1727&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 - 2005-03-31 N1 - Date created - 2005-03-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Science. 2005 Mar 18;307(5716):1773-6 [15774758] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Purified Bacillus anthracis Lethal Toxin Complex Formed in Vitro and during Infection Exhibits Functional and Biological Activity AN - 17482917; 6189550 AB - Anthrax protective antigen (PA, 83 kDa), a pore-forming protein, upon protease activation to 63 kDa (PA sub(63)), translocates lethal factor (LF) and edema factor (EF) from endosomes into the cytosol of the cell. The relatively small size of the heptameric PA sub(63) pore ([approx]12 Aa) raises questions as to how large molecules such as LF and EF can move through the pore. In addition, the reported high binding affinity between PA and EF/LF suggests that EF/LF may not dissociate but remain complexed with activated PA sub(63). In this study, we found that purified (PA sub(63)) sub(7)-LF complex exhibited biological and functional activities similar to the free LF. Purified LF complexed with PA sub(63) heptamer was able to cleave both a synthetic peptide substrate and endogenous mitogen-activated protein kinase kinase substrates and kill susceptible macrophage cells. Electrophysiological studies of the complex showed strong rectification of the ionic current at positive voltages, an effect similar to that observed if LF is added to the channels formed by heptameric PA sub(63) pore. Complexes of (PA sub(63)) sub(7)-LF found in the plasma of infected animals showed functional activity. Identifying active complex in the blood of infected animals has important implications for therapeutic design, especially those directed against PA and LF. Our studies suggest that the individual toxin components and the complex must be considered as critical targets for anthrax therapeutics. JF - Journal of Biological Chemistry AU - Panchal, Rekha G AU - Halverson, Kelly M AU - Ribot, Wilson AU - Lane, Douglas AU - Kenny, Tara AU - Abshire, Teresa G AU - Ezzell, John W AU - Hoover, Timothy A AU - Powell, Bradford AU - Little, Stephen AU - Kasianowicz, John J AU - Bavari, Sina AD - Developmental Therapeutics Program, Target Structure-based Drug Discovery Group, NCI SAIC-Frederick, National Institutes of Health, Frederick, Maryland Y1 - 2005/03/18/ PY - 2005 DA - 2005 Mar 18 SP - 10834 EP - 10839 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 - 280 IS - 11 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts B: Bacteriology KW - Macrophages KW - MAP kinase KW - synthetic peptides KW - Channel pores KW - Lethal factor KW - protective antigen KW - Edema KW - pore-forming proteins KW - Bacillus anthracis KW - Toxins KW - endosomes KW - Anthrax KW - Proteinase KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17482917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Purified+Bacillus+anthracis+Lethal+Toxin+Complex+Formed+in+Vitro+and+during+Infection+Exhibits+Functional+and+Biological+Activity&rft.au=Panchal%2C+Rekha+G%3BHalverson%2C+Kelly+M%3BRibot%2C+Wilson%3BLane%2C+Douglas%3BKenny%2C+Tara%3BAbshire%2C+Teresa+G%3BEzzell%2C+John+W%3BHoover%2C+Timothy+A%3BPowell%2C+Bradford%3BLittle%2C+Stephen%3BKasianowicz%2C+John+J%3BBavari%2C+Sina&rft.aulast=Panchal&rft.aufirst=Rekha&rft.date=2005-03-18&rft.volume=280&rft.issue=11&rft.spage=10834&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus anthracis; Channel pores; Toxins; Anthrax; Proteinase; protective antigen; MAP kinase; synthetic peptides; Macrophages; Edema; pore-forming proteins; endosomes; Lethal factor ER - TY - JOUR T1 - Deriving the glutamate clearance time course from transporter currents in CA1 hippocampal astrocytes: transmitter uptake gets faster during development. AN - 67527890; 15772350 AB - At many excitatory synapses, the neurotransmitter glutamate diffuses beyond the synaptic cleft to activate extrasynaptic targets. The extent and impact of such transmitter "spillover" on the processing capacity of neuronal networks are unclear, in part because it remains unknown how far transmitter diffuses from its point of release before being removed from the extracellular space by high-affinity glutamate transporters. Synaptically activated, transporter-mediated currents (STCs) recorded in hippocampal astrocytes provide an experimental measure of glutamate uptake, but the time course of the STC may be shaped, or "filtered," by other factors and therefore not represent a direct indication of clearance rate. Here, STCs were recorded from astrocytes in rat hippocampal slices under conditions in which uptake capacity was reduced and the STC decay reflected a slowed rate of glutamate clearance. The temporal characteristics of the filtering mechanisms were extracted from these responses, and the glutamate clearance time course in control conditions was derived. The results indicate that glutamate can be cleared from the extrasynaptic space within 1 ms. Clearance is fastest in adult neuropil, corresponding to a developmental increase in glial transporter expression. Synaptically released glutamate is taken up at the same rate as glutamate released via flash photolysis, indicating that the spatial location of transporters relative to the site of glutamate release does not affect the time course of clearance. Slower clearance in young animals would permit glutamate to diffuse greater distances, indicating a particularly important role for extrasynaptic receptors early in development. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Diamond, Jeffrey S AD - Synaptic Physiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3701, USA. diamondj@ninds.nih.gov Y1 - 2005/03/16/ PY - 2005 DA - 2005 Mar 16 SP - 2906 EP - 2916 VL - 25 IS - 11 KW - Amino Acid Transport System X-AG KW - 0 KW - Excitatory Amino Acid Antagonists KW - Glutamates KW - alpha-(4,5-dimethoxy-2-nitrobenzyl) glutamate KW - benzyloxyaspartate KW - Picrotoxin KW - 124-87-8 KW - Aspartic Acid KW - 30KYC7MIAI KW - Glutamic Acid KW - 3KX376GY7L KW - picrotoxinin KW - 9K011NUF0R KW - Index Medicus KW - Patch-Clamp Techniques -- methods KW - Animals KW - Membrane Potentials -- radiation effects KW - Age Factors KW - Electric Stimulation -- methods KW - Dose-Response Relationship, Drug KW - Dose-Response Relationship, Radiation KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Rats KW - Animals, Newborn KW - Aspartic Acid -- pharmacology KW - Rats, Sprague-Dawley KW - Excitatory Postsynaptic Potentials -- drug effects KW - Glutamates -- pharmacology KW - Excitatory Postsynaptic Potentials -- radiation effects KW - Picrotoxin -- pharmacology KW - In Vitro Techniques KW - Picrotoxin -- analogs & derivatives KW - Amino Acid Transport System X-AG -- antagonists & inhibitors KW - Time Factors KW - Male KW - Excitatory Postsynaptic Potentials -- physiology KW - Synapses -- physiology KW - Glutamic Acid -- metabolism KW - Synapses -- drug effects KW - Hippocampus -- growth & development KW - Synapses -- radiation effects KW - Hippocampus -- cytology KW - Astrocytes -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67527890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Deriving+the+glutamate+clearance+time+course+from+transporter+currents+in+CA1+hippocampal+astrocytes%3A+transmitter+uptake+gets+faster+during+development.&rft.au=Diamond%2C+Jeffrey+S&rft.aulast=Diamond&rft.aufirst=Jeffrey&rft.date=2005-03-16&rft.volume=25&rft.issue=11&rft.spage=2906&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 - 2006-03-13 N1 - Date created - 2005-03-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: J Neurosci. 2005 Apr 6;25(14):3739 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A chimeric protein induces tumor cell apoptosis by delivering the human Bcl-2 family BH3-only protein Bad. AN - 67493969; 15751984 AB - Deregulation of PI3K/Akt and Raf/Mek/Erk signal transduction cascades is one of the principal causes of neoplastic transformation. The inactivation of the proapoptotic protein Bad, upon phosphorylation by different kinases of these two pathways, may play an important role in different human malignancies. Therefore, we have expressed and purified a new chimeric protein, hGM-CSF-Bad, linking the human granulocyte-macrophage colony-stimulating factor to the N-terminus of the proapoptotic protein human Bad, to deliver Bad into tumor cells and induce apoptosis. Indeed, the human GM-CSF receptor is a good target because it is overexpressed on many leukemias and solid tumors and is not detectable on stem cells. We found that the chimeric protein binds the human GM-CSF receptor, is endocytosed, and appears to reach the cytosol via retrograde ER transport. After entering cells, the protein is able to induce apoptosis of human leukemia cells and human colon and gastric carcinoma cell lines (IC(50) values as low as 1 muM). We conclude that GM-CSF-Bad can overcome the inappropriate survival stimuli in transformed cells and restore the apoptotic pathway. The completely human sequence and the elevated selectivity for cancer cells could prevent immunogenicity and the nonspecific toxicity of targeted toxins in future clinical application of this fusion protein. JF - Biochemistry AU - Antignani, Antonella AU - Youle, Richard J AD - Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3704, USA. Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 SP - 4074 EP - 4082 VL - 44 IS - 10 SN - 0006-2960, 0006-2960 KW - BAD protein, human KW - 0 KW - BH3 Interacting Domain Death Agonist Protein KW - BID protein, human KW - Carrier Proteins KW - Growth Inhibitors KW - Proto-Oncogene Proteins c-bcl-2 KW - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor KW - Recombinant Fusion Proteins KW - bcl-Associated Death Protein KW - Serine KW - 452VLY9402 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Cell Survival -- genetics KW - HL-60 Cells KW - HeLa Cells KW - Humans KW - Granulocyte-Macrophage Colony-Stimulating Factor -- toxicity KW - Growth Inhibitors -- genetics KW - Intracellular Fluid -- metabolism KW - Cell Line, Tumor KW - Serine -- genetics KW - Growth Inhibitors -- toxicity KW - Protein Structure, Tertiary -- genetics KW - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor -- metabolism KW - Protein Transport -- genetics KW - Phosphorylation KW - Granulocyte-Macrophage Colony-Stimulating Factor -- genetics KW - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor -- genetics KW - Alanine -- genetics KW - Granulocyte-Macrophage Colony-Stimulating Factor -- metabolism KW - U937 Cells KW - Growth Inhibitors -- metabolism KW - Recombinant Fusion Proteins -- metabolism KW - Apoptosis -- genetics KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- genetics KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Carrier Proteins -- toxicity KW - Carrier Proteins -- physiology KW - Recombinant Fusion Proteins -- toxicity KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Recombinant Fusion Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67493969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chimeric+protein+induces+tumor+cell+apoptosis+by+delivering+the+human+Bcl-2+family+BH3-only+protein+Bad.&rft.au=Antignani%2C+Antonella%3BYoule%2C+Richard+J&rft.aulast=Antignani&rft.aufirst=Antonella&rft.date=2005-03-15&rft.volume=44&rft.issue=10&rft.spage=4074&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-07 N1 - Date created - 2005-03-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? AN - 67450110; 15721980 AB - Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg i.p.) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects. JF - Free radical biology & medicine AU - Kadiiska, M B AU - Gladen, B C AU - Baird, D D AU - Germolec, D AU - Graham, L B AU - Parker, C E AU - Nyska, A AU - Wachsman, J T AU - Ames, B N AU - Basu, S AU - Brot, N AU - Fitzgerald, G A AU - Floyd, R A AU - George, M AU - Heinecke, J W AU - Hatch, G E AU - Hensley, K AU - Lawson, J A AU - Marnett, L J AU - Morrow, J D AU - Murray, D M AU - Plastaras, J AU - Roberts, L J AU - Rokach, J AU - Shigenaga, M K AU - Sohal, R S AU - Sun, J AU - Tice, R R AU - Van Thiel, D H AU - Wellner, D AU - Walter, P B AU - Tomer, K B AU - Mason, R P AU - Barrett, J C AD - Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, MD F0-02, Research Triangle Park, NC 27709, USA. Kadiiska@niehs.nih.gov Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 SP - 698 EP - 710 VL - 38 IS - 6 SN - 0891-5849, 0891-5849 KW - Free Radicals KW - 0 KW - Thiobarbituric Acid Reactive Substances KW - Tyrosine KW - 42HK56048U KW - Malondialdehyde KW - 4Y8F71G49Q KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - DNA KW - 9007-49-2 KW - Methionine KW - AE28F7PNPL KW - Hydrogen Peroxide KW - BBX060AN9V KW - Carbon Tetrachloride KW - CL2T97X0V0 KW - Deoxyguanosine KW - G9481N71RO KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Comet Assay KW - Immunoblotting KW - DNA Damage KW - Oxygen -- metabolism KW - Hydrogen Peroxide -- metabolism KW - Methionine -- metabolism KW - Liver -- metabolism KW - Tyrosine -- chemistry KW - Rats KW - Rats, Inbred F344 KW - Malondialdehyde -- pharmacology KW - Gas Chromatography-Mass Spectrometry KW - Spectrophotometry KW - Tyrosine -- metabolism KW - Time Factors KW - Male KW - Immunoassay KW - Carbon Tetrachloride Poisoning -- metabolism KW - DNA -- metabolism KW - Oxidative Stress KW - Deoxyguanosine -- pharmacology KW - Carbon Tetrachloride -- toxicity KW - Lipid Metabolism KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67450110?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Biomarkers+of+oxidative+stress+study+II%3A+are+oxidation+products+of+lipids%2C+proteins%2C+and+DNA+markers+of+CCl4+poisoning%3F&rft.au=Kadiiska%2C+M+B%3BGladen%2C+B+C%3BBaird%2C+D+D%3BGermolec%2C+D%3BGraham%2C+L+B%3BParker%2C+C+E%3BNyska%2C+A%3BWachsman%2C+J+T%3BAmes%2C+B+N%3BBasu%2C+S%3BBrot%2C+N%3BFitzgerald%2C+G+A%3BFloyd%2C+R+A%3BGeorge%2C+M%3BHeinecke%2C+J+W%3BHatch%2C+G+E%3BHensley%2C+K%3BLawson%2C+J+A%3BMarnett%2C+L+J%3BMorrow%2C+J+D%3BMurray%2C+D+M%3BPlastaras%2C+J%3BRoberts%2C+L+J%3BRokach%2C+J%3BShigenaga%2C+M+K%3BSohal%2C+R+S%3BSun%2C+J%3BTice%2C+R+R%3BVan+Thiel%2C+D+H%3BWellner%2C+D%3BWalter%2C+P+B%3BTomer%2C+K+B%3BMason%2C+R+P%3BBarrett%2C+J+C&rft.aulast=Kadiiska&rft.aufirst=M&rft.date=2005-03-15&rft.volume=38&rft.issue=6&rft.spage=698&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 - 2005-06-28 N1 - Date created - 2005-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning. AN - 67445853; 15721981 AB - Plasma and urinary levels of malondialdehyde-like products (MDA) and isoprostanes were identified as markers of in vivo lipid peroxidation in an animal model of CCl4 poisoning. We sought to determine the extent to which the formation of these oxidation products is influenced by inhibition of the cyclooxygenase enzymes which catalytically generate proinflammatory lipid peroxidation products known as prostaglandins and thromboxane. In the present studies, after induction of oxidant stress in rats with CCl4, lipid peroxidation products measured in plasma and urine demonstrate that isoprostanes and MDA can be partially inhibited by cyclooxygenase inhibitors, albeit to different extents. The lowering of isoprostane and MDA formation, however, may not to due primarily to the diminution of catalytic generation of isoprostanes or MDA by the cyclooxygenases but, rather, may be the result of the suppression of nonenzymatic lipid peroxidation. This is suggested since 8,12-iso-iPF2alpha-VI is also reduced by indomethacin, yet, unlike other isoprostanes and MDA, it is not generated catalytically by the cyclooxygenase. Thus, although the two cyclooxygenase inhibitors we tested have statistically significant effects on the measurements of both isoprostanes and MDA in this study, the results provide evidence that these lipid-degradation products primarily constitute markers of oxidative stress. JF - Free radical biology & medicine AU - Kadiiska, M B AU - Gladen, B C AU - Baird, D D AU - Graham, L B AU - Parker, C E AU - Ames, B N AU - Basu, S AU - Fitzgerald, G A AU - Lawson, J A AU - Marnett, L J AU - Morrow, J D AU - Murray, D M AU - Plastaras, J AU - Roberts, L J AU - Rokach, J AU - Shigenaga, M K AU - Sun, J AU - Walter, P B AU - Tomer, K B AU - Barrett, J C AU - Mason, R P AD - National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA. Kadiiska@niehs.nih.gov Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 SP - 711 EP - 718 VL - 38 IS - 6 SN - 0891-5849, 0891-5849 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Biomarkers KW - Free Radicals KW - Prostaglandins KW - Protein Isoforms KW - Meclofenamic Acid KW - 48I5LU4ZWD KW - Thromboxane A2 KW - 57576-52-0 KW - Carbon Tetrachloride KW - CL2T97X0V0 KW - Oxygen KW - S88TT14065 KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Animals KW - Mass Spectrometry KW - Oxygen -- metabolism KW - Lipid Peroxidation KW - Chromatography, High Pressure Liquid KW - Inflammation KW - Rats KW - Rats, Inbred F344 KW - Thromboxane A2 -- metabolism KW - Gas Chromatography-Mass Spectrometry KW - Time Factors KW - Prostaglandins -- metabolism KW - Immunoassay KW - Meclofenamic Acid -- pharmacology KW - Indomethacin -- metabolism KW - Oxidative Stress KW - Carbon Tetrachloride Poisoning -- drug therapy KW - Biomarkers -- metabolism KW - Carbon Tetrachloride -- toxicity KW - Lipid Metabolism KW - Indomethacin -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67445853?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regions+of+the+varicella-zoster+virus+open+reading+frame+63+latency-associated+protein+important+for+replication+in+vitro+are+also+critical+for+efficient+establishment+of+latency.&rft.au=Cohen%2C+Jeffrey+I%3BKrogmann%2C+Tammy%3BBontems%2C+Sebastien%3BSadzot-Delvaux%2C+Catherine%3BPesnicak%2C+Lesley&rft.aulast=Cohen&rft.aufirst=Jeffrey&rft.date=2005-04-01&rft.volume=79&rft.issue=8&rft.spage=5069&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 - 2005-06-28 N1 - Date created - 2005-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Advances in MR elastic displacement imaging and non-invasive measurements of myocardial compliance AN - 40040348; 3924611 AU - Wen, H Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 7000:Multidisciplinary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/40040348?accountid=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=Advances+in+MR+elastic+displacement+imaging+and+non-invasive+measurements+of+myocardial+compliance&rft.au=Wen%2C+H&rft.aulast=Wen&rft.aufirst=H&rft.date=2005-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: AVS Science & Technology Society, ; phone: 212 248 0200; fax: 212 248 0245; URL: www.avs.org/ N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Ternary SNARE complexes are associated with lipid rafts in RBL mast cells AN - 40022528; 3915301 AU - Puri, N AU - Roche, P A Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/40022528?accountid=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=Ternary+SNARE+complexes+are+associated+with+lipid+rafts+in+RBL+mast+cells&rft.au=Puri%2C+N%3BRoche%2C+P+A&rft.aulast=Puri&rft.aufirst=N&rft.date=2005-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Avenue, Suite 750, Bethesda, MD 20814-2762, USA; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Functional architecture of the ATP-dependent Clp proteases: Discrimination of static and mobile elements by cryo-electron microscopy AN - 40017228; 3915455 AU - Ishikawa, T AU - Maurizi, M R AU - Steven, A C Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/40017228?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Hormones+and+endometrial+cancer--new+data+from+the+Million+Women+Study.&rft.au=Brinton%2C+Louise+A%3BLacey%2C+James+V%3BTrimble%2C+Edward+L&rft.aulast=Brinton&rft.aufirst=Louise&rft.date=2005-04-01&rft.volume=365&rft.issue=9470&rft.spage=1517&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=1474-547X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Avenue, Suite 750, Bethesda, MD 20814-2762, USA; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Evidence for endoplasmic reticulum origins of peroxisomes AN - 40014351; 3915506 AU - Kim, P K AU - Mullen, R T AU - Lippincott-Schwartz, J Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/40014351?accountid=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=Evidence+for+endoplasmic+reticulum+origins+of+peroxisomes&rft.au=Kim%2C+P+K%3BMullen%2C+R+T%3BLippincott-Schwartz%2C+J&rft.aulast=Kim&rft.aufirst=P&rft.date=2005-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Avenue, Suite 750, Bethesda, MD 20814-2762, USA; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Depletion of GAK/Auxilin 2 by RNAi: Effect on clathrin distribution and receptor mediated endocytosis AN - 39998705; 3915318 AU - Lee, D AU - Zhao, X AU - Greene, L AU - Eisenberg, E Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39998705?accountid=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=Depletion+of+GAK%2FAuxilin+2+by+RNAi%3A+Effect+on+clathrin+distribution+and+receptor+mediated+endocytosis&rft.au=Lee%2C+D%3BZhao%2C+X%3BGreene%2C+L%3BEisenberg%2C+E&rft.aulast=Lee&rft.aufirst=D&rft.date=2005-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Avenue, Suite 750, Bethesda, MD 20814-2762, USA; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Quantitative analysis of microtubule polymerization in extracellular matrix-mediated axon guidance AN - 39968629; 3915174 AU - Vartanian, K AU - Katagiri, Y AU - Peter, P AU - Tan, F AU - Wang, H AU - Geller, H M Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39968629?accountid=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=Quantitative+analysis+of+microtubule+polymerization+in+extracellular+matrix-mediated+axon+guidance&rft.au=Vartanian%2C+K%3BKatagiri%2C+Y%3BPeter%2C+P%3BTan%2C+F%3BWang%2C+H%3BGeller%2C+H+M&rft.aulast=Vartanian&rft.aufirst=K&rft.date=2005-03-15&rft.volume=&rft.issue=4&rft.spage=401&rft.isbn=&rft.btitle=&rft.title=Medical+care&rft.issn=00257079&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Avenue, Suite 750, Bethesda, MD 20814-2762, USA; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Fusion pathway mediated by sindbis virus E1 glycoprotein: Membrane intermediates and capsid-envelope interactions AN - 39966181; 3915287 AU - Zaitseva, E AU - Mittal, A AU - Griffin, D AU - Chernomordik, L Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39966181?accountid=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=Fusion+pathway+mediated+by+sindbis+virus+E1+glycoprotein%3A+Membrane+intermediates+and+capsid-envelope+interactions&rft.au=Zaitseva%2C+E%3BMittal%2C+A%3BGriffin%2C+D%3BChernomordik%2C+L&rft.aulast=Zaitseva&rft.aufirst=E&rft.date=2005-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Avenue, Suite 750, Bethesda, MD 20814-2762, USA; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Retrocyclin-2 inhibits early stages of membrane fusion reactions mediated by envelope glycoproteins of diverse viruses AN - 39953975; 3915288 AU - Leikina, E AU - Melikov, K AU - Delanoe, H AU - Waring, A J AU - Lehrer, R I AU - Chernomordik, LV Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39953975?accountid=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=Retrocyclin-2+inhibits+early+stages+of+membrane+fusion+reactions+mediated+by+envelope+glycoproteins+of+diverse+viruses&rft.au=Leikina%2C+E%3BMelikov%2C+K%3BDelanoe%2C+H%3BWaring%2C+A+J%3BLehrer%2C+R+I%3BChernomordik%2C+LV&rft.aulast=Leikina&rft.aufirst=E&rft.date=2005-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Avenue, Suite 750, Bethesda, MD 20814-2762, USA; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - T cells' signaling machinery sets the threshold for sensitive and fast self/nonself discrimination AN - 39925920; 3915495 AU - Altan-Bonnet, G AU - Stefanova, I AU - Germain, R N Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39925920?accountid=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=T+cells%27+signaling+machinery+sets+the+threshold+for+sensitive+and+fast+self%2Fnonself+discrimination&rft.au=Altan-Bonnet%2C+G%3BStefanova%2C+I%3BGermain%2C+R+N&rft.aulast=Altan-Bonnet&rft.aufirst=G&rft.date=2005-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Avenue, Suite 750, Bethesda, MD 20814-2762, USA; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Characterization of early stages of nuclear envelope assembly driven by cytosolic proteins AN - 39902450; 3915337 AU - Ramos, C AU - Melikov, K C AU - Zaitseva, E AU - Wilson, K L AU - Chernomordik, LV Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39902450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cancer+therapeutics&rft.atitle=Inhibition+of+the+epidermal+growth+factor+receptor+increases+expression+of+genes+that+stimulate+inflammation%2C+apoptosis%2C+and+cell+attachment.&rft.au=Woodworth%2C+Craig+D%3BMichael%2C+Evan%3BMarker%2C+Dan%3BAllen%2C+Sarah%3BSmith%2C+Laura%3BNees%2C+Matthias&rft.aulast=Woodworth&rft.aufirst=Craig&rft.date=2005-04-01&rft.volume=4&rft.issue=4&rft.spage=650&rft.isbn=&rft.btitle=&rft.title=Molecular+cancer+therapeutics&rft.issn=15357163&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Avenue, Suite 750, Bethesda, MD 20814-2762, USA; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - High-throughput antibody screening of clinical serum samples AN - 39896989; 3915449 AU - Gannot, G AU - Tangrea, MA AU - Gillespie, J W AU - Erickson, H S AU - Wallis, B S AU - Knezevic, V AU - Hartmann, D P AU - Chuaqui, R F AU - Emmert-Buck, M R Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39896989?accountid=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=High-throughput+antibody+screening+of+clinical+serum+samples&rft.au=Gannot%2C+G%3BTangrea%2C+MA%3BGillespie%2C+J+W%3BErickson%2C+H+S%3BWallis%2C+B+S%3BKnezevic%2C+V%3BHartmann%2C+D+P%3BChuaqui%2C+R+F%3BEmmert-Buck%2C+M+R&rft.aulast=Gannot&rft.aufirst=G&rft.date=2005-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Avenue, Suite 750, Bethesda, MD 20814-2762, USA; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Isoform specific glycosylation of tau by O-linked GlcNAc transferase: Implications for tauopathies AN - 39892797; 3914976 AU - Lazarus, B D AU - Hanover, JA Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39892797?accountid=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=Isoform+specific+glycosylation+of+tau+by+O-linked+GlcNAc+transferase%3A+Implications+for+tauopathies&rft.au=Lazarus%2C+B+D%3BHanover%2C+JA&rft.aulast=Lazarus&rft.aufirst=B&rft.date=2005-03-15&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: American Society for Cell Biology, 8120 Woodmont Avenue, Suite 750, Bethesda, MD 20814-2762, USA; email: ascbinfo@ascb.org; URL: www.ascb.org N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Large-Scale Molecular Characterization of Adeno-Associated Virus Vector Integration in Mouse Liver AN - 17288716; 6173442 AB - Recombinant adeno-associated virus (rAAV) vector holds promise for gene therapy. Despite a low frequency of chromosomal integration of vector genomes, recent studies have raised concerns about the risk of rAAV integration because integration occurs preferentially in genes and accompanies chromosomal deletions, which may lead to loss-of-function insertional mutagenesis. Here, by analyzing 347 rAAV integrations in mice, we elucidate novel features of rAAV integration: the presence of hot spots for integration and a strong preference for integrating near gene regulatory sequences. The most prominent hot spot was a harmless chromosomal niche in the rRNA gene repeats, whereas nearly half of the integrations landed near transcription start sites or CpG islands, suggesting the possibility of activating flanking cellular disease genes by vector integration, similar to retroviral gain-of-function insertional mutagenesis. Possible cancer-related genes were hit by rAAV integration at a frequency of 3.5%. In addition, the information about chromosomal changes at 218 integration sites and 602 breakpoints of vector genomes have provided a clue to how vector terminal repeats and host chromosomal DNA are joined in the integration process. Thus, the present study provides new insights into the risk of rAAV-mediated insertional mutagenesis and the mechanisms of rAAV integration. JF - Journal of Virology AU - Nakai, Hiroyuki AU - Wu, Xiaolin AU - Fuess, Sally AU - Storm, Theresa A AU - Munroe, David AU - Montini, Eugenio AU - Burgess, Shawn M AU - Grompe, Markus AU - Kay, Mark A AD - Departments of Pediatrics. Genetics, Stanford University School of Medicine, Stanford, California. Laboratory of Molecular Technology, SAIC-Frederick, National Cancer Institute-Frederick, Frederick. Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland. Departments of Molecular and Medical Genetics. Pediatrics, Oregon Health & Science University, Portland, Oregon Y1 - 2005/03/15/ PY - 2005 DA - 2005 Mar 15 SP - 3606 EP - 3614 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 79 IS - 6 SN - 0022-538X, 0022-538X KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Genomes KW - Hot spots KW - Adeno-associated virus KW - Expression vectors KW - Breakpoints KW - rRNA KW - Integration KW - insertional mutagenesis KW - Gene therapy KW - Regulatory sequences KW - Transcription KW - CpG islands KW - Chromosome deletion KW - Liver KW - W3 33181:Gene therapy vectors KW - V 22050:Viral genetics including virus reactivation KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17288716?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Large-Scale+Molecular+Characterization+of+Adeno-Associated+Virus+Vector+Integration+in+Mouse+Liver&rft.au=Nakai%2C+Hiroyuki%3BWu%2C+Xiaolin%3BFuess%2C+Sally%3BStorm%2C+Theresa+A%3BMunroe%2C+David%3BMontini%2C+Eugenio%3BBurgess%2C+Shawn+M%3BGrompe%2C+Markus%3BKay%2C+Mark+A&rft.aulast=Nakai&rft.aufirst=Hiroyuki&rft.date=2005-03-15&rft.volume=79&rft.issue=6&rft.spage=3606&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adeno-associated virus; Integration; insertional mutagenesis; Hot spots; Genomes; CpG islands; rRNA; Chromosome deletion; Regulatory sequences; Transcription; Expression vectors; Liver; Breakpoints; Gene therapy ER - TY - JOUR T1 - Thiazide diuretics and the risk of gallbladder disease requiring surgery in women. AN - 67515179; 15767534 AB - Previous studies have suggested that thiazide diuretic use increases the risk of cholecystitis. We prospectively examined the association between thiazide use and cholecystectomy, a surrogate for symptomatic cholelithiasis, in a cohort of 81 351 US women who were aged 30 to 55 years in 1980 and followed up to 2000. Regular use of thiazide diuretics was assessed at baseline by asking the participants to report whether they currently took "any of the following medications in most weeks" and listing "thiazide diuretics (eg, Diuril and Hydrodiuril)" among other drugs. Respondents were also requested to report the duration of thiazide diuretic use. Assessment of thiazide diuretic use was updated in 1982, 1988, 1994, 1996, and 1998. Cox regression was used to adjust simultaneously for other potential risk factors for cholecystectomy. During follow-up, 8607 women reported undergoing a cholecystectomy. A modest positive relation between the use of thiazide diuretics and cholecystectomy was observed. Compared with never users of thiazide diuretics, the multivariate relative risk of cholecystectomy for past users was 1.16 (95% confidence interval,1.08-1.24) and the multivariate relative risk for current users was 1.39 (95% confidence interval, 1.29-1.50). These findings are compatible with the hypothesis that the use of thiazide diuretics increases the risk of symptomatic cholecystitis. However, we cannot rule out the possibility that our results are in part explained by unconsidered factors related to the indication for antihypertensive therapy or by differences in medical surveillance between users and nonusers of thiazide diuretics. JF - Archives of internal medicine AU - Leitzmann, Michael F AU - Tsai, Chung-Jyi AU - Stampfer, Meir J AU - Willett, Walter C AU - Giovannucci, Edward AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, EPS-MSC 7232, 6120 Executive Boulevard, Bethesda, MD 20892, USA. leitzmann@mail.nih.gov Y1 - 2005/03/14/ PY - 2005 DA - 2005 Mar 14 SP - 567 EP - 573 VL - 165 IS - 5 SN - 0003-9926, 0003-9926 KW - Benzothiadiazines KW - 0 KW - Diuretics KW - Sodium Chloride Symporter Inhibitors KW - Abridged Index Medicus KW - Index Medicus KW - Risk KW - Prospective Studies KW - Humans KW - Cohort Studies KW - Adult KW - Incidence KW - Middle Aged KW - Cholecystectomy -- statistics & numerical data KW - Time Factors KW - Female KW - Proportional Hazards Models KW - Multivariate Analysis KW - Cholecystitis -- chemically induced KW - Sodium Chloride Symporter Inhibitors -- adverse effects KW - Cholecystitis -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67515179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thiazide+diuretics+and+the+risk+of+gallbladder+disease+requiring+surgery+in+women.&rft.au=Leitzmann%2C+Michael+F%3BTsai%2C+Chung-Jyi%3BStampfer%2C+Meir+J%3BWillett%2C+Walter+C%3BGiovannucci%2C+Edward&rft.aulast=Leitzmann&rft.aufirst=Michael&rft.date=2005-03-14&rft.volume=165&rft.issue=5&rft.spage=567&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 - 2005-04-05 N1 - Date created - 2005-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of nandrolone decanoate therapy on weight and lean body mass in HIV-infected women with weight loss: a randomized, double-blind, placebo-controlled, multicenter trial. AN - 67513524; 15767536 AB - Weight loss is associated with accelerated mortality and disease progression in patients with human immunodeficiency virus (HIV) infection. Although studies have examined a variety of anabolic therapies in HIV-infected men, the safety and efficacy of such treatments in women have not been adequately studied. In this randomized, double-blind, placebo-controlled, multicenter, phase I/II study, 38 HIV-infected women with documented weight loss of 5% or greater in the preceding year or a body mass index of less than 20 kg/m(2) were randomized to receive nandrolone decanoate (100 mg) or an equivalent volume of placebo every other week by intramuscular injection. Subjects received blinded treatment for 12 weeks, followed by open-label therapy for 12 weeks. Lean body mass and fat (bioelectrical impedance analysis) and weight were measured at baseline and at weeks 6, 12, 18, and 24. Biochemical assessments of safety (hematologic analyses, liver function tests, and sex hormone measurements) were performed at these same time points. Clinical signs and symptoms were monitored biweekly. Subjects randomized to receive nandrolone had significant increases in weight and lean body mass during blinded treatment (4.6 kg [9.0%] and 3.5 kg [8.6%], respectively; P<.001 vs baseline and placebo in each case). Fat mass did not change statistically significantly in either group. Although there were no statistically significant differences between groups in biochemical measures, the number of grade 3 or greater toxicities, or reports of virilizing effects, a full assessment of safety cannot be made in a trial of this size. Nandrolone decanoate therapy may prove to be generally safe and beneficial in reversing weight loss and lean tissue loss in women with HIV infection and other chronic catabolic diseases. JF - Archives of internal medicine AU - Mulligan, Kathleen AU - Zackin, Robert AU - Clark, Rebecca A AU - Alston-Smith, Beverly AU - Liu, Tun AU - Sattler, Fred R AU - Delvers, Thomas B AU - Currier, Judith S AU - AIDS Clinical Trials Group 329 Study Team AU - National Institute of Allergy and Infectious Diseases Adult AIDS Clinical Trials Group AD - Division of Endocrinology, San Francisco General Hospital, 1001 Potrero Avenue, Rm. 3501K, San Francisco, CA 94110, USA. kmulligan@sfghgcrc.ucsf.edu ; AIDS Clinical Trials Group 329 Study Team ; National Institute of Allergy and Infectious Diseases Adult AIDS Clinical Trials Group Y1 - 2005/03/14/ PY - 2005 DA - 2005 Mar 14 SP - 578 EP - 585 VL - 165 IS - 5 SN - 0003-9926, 0003-9926 KW - Anabolic Agents KW - 0 KW - Hormones KW - Nandrolone KW - 6PG9VR430D KW - nandrolone decanoate KW - H45187T098 KW - Abridged Index Medicus KW - Index Medicus KW - Nutritional Status KW - Blood Chemical Analysis KW - Double-Blind Method KW - Humans KW - Safety KW - Injections, Intramuscular KW - Hormones -- blood KW - Body Mass Index KW - Hematologic Tests KW - Placebo Effect KW - Adult KW - Body Weight -- drug effects KW - Treatment Outcome KW - Female KW - HIV Wasting Syndrome -- blood KW - HIV Wasting Syndrome -- drug therapy KW - Anabolic Agents -- therapeutic use KW - Nandrolone -- analogs & derivatives KW - Nandrolone -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67513524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+nandrolone+decanoate+therapy+on+weight+and+lean+body+mass+in+HIV-infected+women+with+weight+loss%3A+a+randomized%2C+double-blind%2C+placebo-controlled%2C+multicenter+trial.&rft.au=Mulligan%2C+Kathleen%3BZackin%2C+Robert%3BClark%2C+Rebecca+A%3BAlston-Smith%2C+Beverly%3BLiu%2C+Tun%3BSattler%2C+Fred+R%3BDelvers%2C+Thomas+B%3BCurrier%2C+Judith+S%3BAIDS+Clinical+Trials+Group+329+Study+Team%3BNational+Institute+of+Allergy+and+Infectious+Diseases+Adult+AIDS+Clinical+Trials+Group&rft.aulast=Mulligan&rft.aufirst=Kathleen&rft.date=2005-04-01&rft.volume=30&rft.issue=4&rft.spage=720&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 - 2005-04-05 N1 - Date created - 2005-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metal-catalyzed oxidation of alpha-synuclein: helping to define the relationship between oligomers, protofibrils, and filaments. AN - 67487475; 15615715 AB - Oxidative stress is implicated in a number of neuro-degenerative diseases and is associated with the selective loss of dopaminergic neurons of the substantia nigra in Parkinson's disease. The role of alpha-synuclein as a potential target of intracellular oxidants has been demonstrated by the identification of posttranslational modifications of synuclein within intracellular aggregates that accumulate in Parkinson's disease brains, as well as the ability of a number of oxidative insults to induce synuclein oligomerization. The relationship between these relatively small soluble oligomers, potentially neurotoxic synuclein protofibrils, and synuclein filaments remains unclear. We have found that metal-catalyzed oxidation of alpha-synuclein inhibited formation of synuclein filaments with a concomitant accumulation of beta sheet-rich oligomers that may represent synuclein protofibrils. Similar results with a number of oxidative and enzymatic treatments suggest that the covalent association of synuclein into higher molecular mass oligomers/protofibrils represents an alternate pathway from filament formation and renders synuclein less prone to proteasomal degradation. JF - The Journal of biological chemistry AU - Cole, Nelson B AU - Murphy, Diane D AU - Lebowitz, Jacob AU - Di Noto, Luca AU - Levine, Rodney L AU - Nussbaum, Robert L AD - Genetic Diseases Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ncole@mail.nih.gov Y1 - 2005/03/11/ PY - 2005 DA - 2005 Mar 11 SP - 9678 EP - 9690 VL - 280 IS - 10 SN - 0021-9258, 0021-9258 KW - Macromolecular Substances KW - 0 KW - Metals KW - Nerve Tissue Proteins KW - Oxidants KW - Recombinant Proteins KW - SNCA protein, human KW - Synucleins KW - alpha-Synuclein KW - Iron KW - E1UOL152H7 KW - Index Medicus KW - Actin Cytoskeleton -- ultrastructure KW - Humans KW - Protein Processing, Post-Translational KW - Parkinson Disease -- metabolism KW - Brain -- metabolism KW - Macromolecular Substances -- metabolism KW - Models, Biological KW - Iron -- metabolism KW - Oxidation-Reduction KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Oxidative Stress KW - Oxidants -- metabolism KW - Recombinant Proteins -- chemistry KW - Macromolecular Substances -- chemistry KW - Nerve Tissue Proteins -- metabolism KW - Metals -- metabolism KW - Nerve Tissue Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67487475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Metal-catalyzed+oxidation+of+alpha-synuclein%3A+helping+to+define+the+relationship+between+oligomers%2C+protofibrils%2C+and+filaments.&rft.au=Cole%2C+Nelson+B%3BMurphy%2C+Diane+D%3BLebowitz%2C+Jacob%3BDi+Noto%2C+Luca%3BLevine%2C+Rodney+L%3BNussbaum%2C+Robert+L&rft.aulast=Cole&rft.aufirst=Nelson&rft.date=2005-03-11&rft.volume=280&rft.issue=10&rft.spage=9678&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 - 2005-04-19 N1 - Date created - 2005-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Salmonella Effector Protein SopB Protects Epithelial Cells from Apoptosis by Sustained Activation of Akt AN - 17617880; 6189892 AB - Invasion of epithelial cells by Salmonella enterica is mediated by bacterial "effector" proteins that are delivered into the host cell by a type III secretion system. Although primarily known for their roles in actin rearrangements and membrane ruffling, translocated effectors also affect host cell processes that are not directly associated with invasion. Here, we show that SopB/SigD, an effector with phosphoinositide phosphatase activity, has anti-apoptotic activity in Salmonella-infected epithelial cells. Salmonella induced the sustained activation of Akt/protein kinase B, a pro-survival kinase, in a SopB-dependent manner. Failure to activate Akt resulted in increased levels of apoptosis after infection with a sopB deletion mutant ( delta sopB). Furthermore, cells infected with wild type bacteria, but not the delta sopB strain, were protected from camptothecin-induced cleavage of caspase-3 and subsequent apoptosis. The anti-apoptotic activity of SopB was dependent on its phosphatase activity, because a catalytically inactive mutant was unable to protect cells from the effects of camptothecin. Finally, small interfering RNA was used to demonstrate the essential role of Akt in SopB-mediated protection against apoptosis. These results provide new insights into the mechanisms of apoptosis and highlight how bacterial effectors can intercept signaling pathways to manipulate host responses. JF - Journal of Biological Chemistry AU - Knodler, Leigh A AU - Finlay, BBrett AU - Steele-Mortimer, Olivia AD - Laboratory of Intracellular Parasites, NIAID, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana Y1 - 2005/03/11/ PY - 2005 DA - 2005 Mar 11 SP - 9058 EP - 9064 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 - 280 IS - 10 SN - 0021-9258, 0021-9258 KW - SigD protein KW - SopB protein KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - G 07320:Bacterial genetics KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17617880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Salmonella+Effector+Protein+SopB+Protects+Epithelial+Cells+from+Apoptosis+by+Sustained+Activation+of+Akt&rft.au=Knodler%2C+Leigh+A%3BFinlay%2C+BBrett%3BSteele-Mortimer%2C+Olivia&rft.aulast=Knodler&rft.aufirst=Leigh&rft.date=2005-03-11&rft.volume=280&rft.issue=10&rft.spage=9058&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-07-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - A receptor domain controls the intracellular sorting of the ferrichrome transporter, ARN1. AN - 67504115; 15719020 AB - The Saccharomyces cerevisiae transporter Arn1p takes up the ferric-siderophore ferrichrome, and extracellular ferrichrome dramatically influences the intracellular trafficking of Arn1p. In the absence of ferrichrome, Arn1p sorts directly to the endosomal compartment. At low concentrations of ferrichrome, Arn1p stably relocalizes to the plasma membrane, yet little to no uptake of ferrichrome occurs at these low concentrations. At higher concentrations of ferrichrome, Arn1p cycles between the plasma membrane and endosome. Arn1p contains two binding sites for ferrichrome: one site has an affinity similar to the K(T) for transport, but the second site has a much higher affinity. Here we report that this high-affinity binding site lies within a unique extracytosolic, carboxyl-terminal domain. Mutations within this domain lead to loss of ferrichrome binding and uptake activities and missorting of Arn1p, including a failure to relocalize to the plasma membrane in the presence of ferrichrome. Mutation of phenylalanine residues in the cytosolic tail of Arn1p also lead to missorting, but without defects in ferrichrome binding. We propose that the carboxyl terminus of Arn1p contains a receptor domain that controls the intracellular trafficking of the transporter. JF - The EMBO journal AU - Kim, Youngwoo AU - Lampert, Sarah M AU - Philpott, Caroline C AD - Liver Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2005/03/09/ PY - 2005 DA - 2005 Mar 09 SP - 952 EP - 962 VL - 24 IS - 5 SN - 0261-4189, 0261-4189 KW - Arn1 protein, S cerevisiae KW - 0 KW - DNA, Fungal KW - Membrane Transport Proteins KW - Saccharomyces cerevisiae Proteins KW - Ubiquitin KW - Ferrichrome KW - 15630-64-5 KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Cytosol -- metabolism KW - Models, Molecular KW - Alanine -- chemistry KW - Biological Transport, Active KW - Models, Biological KW - Mutagenesis, Site-Directed KW - Saccharomyces cerevisiae -- genetics KW - Base Sequence KW - Ubiquitin -- metabolism KW - Ubiquitin -- chemistry KW - Saccharomyces cerevisiae -- metabolism KW - DNA, Fungal -- genetics KW - Binding Sites -- genetics KW - Cell Membrane -- metabolism KW - Protein Structure, Tertiary KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Saccharomyces cerevisiae Proteins -- genetics KW - Membrane Transport Proteins -- chemistry KW - Ferrichrome -- metabolism KW - Saccharomyces cerevisiae Proteins -- chemistry KW - Membrane Transport Proteins -- metabolism KW - Membrane Transport Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67504115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=A+receptor+domain+controls+the+intracellular+sorting+of+the+ferrichrome+transporter%2C+ARN1.&rft.au=Kim%2C+Youngwoo%3BLampert%2C+Sarah+M%3BPhilpott%2C+Caroline+C&rft.aulast=Kim&rft.aufirst=Youngwoo&rft.date=2005-03-09&rft.volume=24&rft.issue=5&rft.spage=952&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 - 2005-04-28 N1 - Date created - 2005-03-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2003 May 13;100(10):5664-9 [12721368] EMBO J. 2003 May 15;22(10):2309-17 [12743025] Science. 2003 Aug 1;301(5633):616-20 [12893936] FEBS Lett. 2003 Nov 27;555(1):96-101 [14630326] Nat Rev Mol Cell Biol. 2004 Jan;5(1):23-32 [14708007] Mol Biol Cell. 2004 Feb;15(2):883-95 [14657252] J Gen Microbiol. 1987 Nov;133(11):3229-36 [3328775] Genetics. 1989 May;122(1):19-27 [2659436] Mol Cell Biol. 1990 May;10(5):2294-301 [2183029] J Biol Chem. 1991 Nov 5;266(31):21150-7 [1718971] Cell. 1994 Jan 28;76(2):403-10 [8293473] Mol Cell Biol. 1994 May;14(5):3065-73 [8164662] J Biol Chem. 1995 Nov 10;270(45):26723-6 [7592901] Science. 1996 Mar 15;271(5255):1552-7 [8599111] EMBO J. 1996 Nov 15;15(22):6084-95 [8947031] Yeast. 1997 Jan;13(1):43-54 [9046086] J Biol Chem. 1997 Aug 22;272(34):21461-6 [9261163] EMBO J. 1998 Sep 1;17(17):5026-36 [9724638] Science. 1998 Dec 18;282(5397):2215-20 [9856937] Nat Struct Biol. 2000 Apr;7(4):287-91 [10742172] Biochem J. 2000 Mar 1;346 Pt 2:329-36 [10677350] Microbiology. 1998 Dec;144 ( Pt 12):3455-62 [9884238] J Biol Chem. 2000 Apr 7;275(14):10709-15 [10744769] FEMS Microbiol Lett. 2000 May 15;186(2):221-7 [10802175] Biometals. 1999 Dec;12(4):301-6 [10816729] J Biol Chem. 2000 May 26;275(21):16354-9 [10748025] Biometals. 2000 Mar;13(1):65-72 [10831226] Mol Biol Cell. 2001 Feb;12(2):421-35 [11179425] Nat Rev Mol Cell Biol. 2001 Mar;2(3):195-201 [11265249] J Biol Chem. 2001 Mar 30;276(13):10218-23 [11120744] Curr Biol. 2001 Nov 13;11(22):R932-4 [11719242] Mol Biol Cell. 2001 Dec;12(12):4129-38 [11739806] EMBO J. 2002 Jul 15;21(14):3632-42 [12110576] Traffic. 2002 Aug;3(8):537-46 [12121417] J Biol Chem. 2002 Aug 23;277(34):30598-605 [12060662] Biochim Biophys Acta. 2003 Feb 17;1610(1):11-22 [12586375] Science. 2003 Aug 1;301(5633):610-5 [12893935] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation of arginine 228 to lysine enhances the glucosyltransferase activity of bovine beta-1,4-galactosyltransferase I. AN - 67470063; 15736931 AB - Beta-1,4-galactosyltransferase I (beta4Gal-T1) normally transfers Gal from UDP-Gal to GlcNAc in the presence of Mn(2+) ion (Gal-T activity) and also transfers Glc from UDP-Glc to GlcNAc (Glc-T activity), albeit at only 0.3% efficiency. In addition, alpha-lactalbumin (LA) enhances this Glc-T activity more than 25 times. Comparison of the crystal structures of UDP-Gal- and UDP-Glc-bound beta4Gal-T1 reveals that the O4 hydroxyl group in both Gal and Glc moieties forms a hydrogen bond with the side chain carboxylate group of Glu317. The orientation of the O4 hydroxyl of glucose causes a steric hindrance to the side chain carboxylate group of Glu317, accounting for the enzyme's low Glc-T activity. In this study, we show that mutation of Arg228, a residue in the vicinity of Glu317, to lysine (R228K-Gal-T1) results in a 15-fold higher Glc-T activity, which is further enhanced by LA to nearly 25% of the Gal-T activity of the wild type. The kinetic parameters indicate that the main effect of the mutation of Arg228 to lysine is on the k(cat) of Glc-T, which increases 3-4-fold, both in the absence and in the presence of LA; simultaneously, the k(cat) for the Gal-T reaction is reduced 30-fold. The crystal structure of R228K-Gal-T1 complexed with LA, UDP-Gal, and Mn(2+) determined at 1.9 A resolution shows that the Asp318 side chain exhibits a minor alternate conformation, compared to that in the wild type. This alternate conformation now causes a steric hindrance to the O4 hydroxyl group of the Gal moiety of UDP-Gal, probably causing the dissociation of UDP-Gal and the reduced k(cat) of the Gal-T reaction. JF - Biochemistry AU - Ramakrishnan, Boopathy AU - Boeggeman, Elizabeth AU - Qasba, Pradman K AD - Structural Glycobiology Section, Laboratory of Experimental and Computational Biology, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201, USA. Y1 - 2005/03/08/ PY - 2005 DA - 2005 Mar 08 SP - 3202 EP - 3210 VL - 44 IS - 9 SN - 0006-2960, 0006-2960 KW - Macromolecular Substances KW - 0 KW - Uridine Diphosphate Galactose KW - 2956-16-3 KW - Manganese KW - 42Z2K6ZL8P KW - Lactalbumin KW - 9013-90-5 KW - Arginine KW - 94ZLA3W45F KW - Galactosyltransferases KW - EC 2.4.1.- KW - Glucosyltransferases KW - beta-1,4-galactosyltransferase I KW - Lysine KW - K3Z4F929H6 KW - Uridine Diphosphate Glucose KW - V50K1D7P4Y KW - Index Medicus KW - Crystallization KW - Animals KW - Lactalbumin -- metabolism KW - Cattle KW - Kinetics KW - Manganese -- chemistry KW - Uridine Diphosphate Galactose -- metabolism KW - Glucosyltransferases -- metabolism KW - Crystallography, X-Ray KW - Macromolecular Substances -- metabolism KW - Uridine Diphosphate Glucose -- metabolism KW - Enzyme Activation -- genetics KW - Mutagenesis, Site-Directed KW - Galactosyltransferases -- metabolism KW - Arginine -- genetics KW - Galactosyltransferases -- genetics KW - Lysine -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67470063?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutation+of+arginine+228+to+lysine+enhances+the+glucosyltransferase+activity+of+bovine+beta-1%2C4-galactosyltransferase+I.&rft.au=Ramakrishnan%2C+Boopathy%3BBoeggeman%2C+Elizabeth%3BQasba%2C+Pradman+K&rft.aulast=Ramakrishnan&rft.aufirst=Boopathy&rft.date=2005-03-08&rft.volume=44&rft.issue=9&rft.spage=3202&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-06 N1 - Date created - 2005-03-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1YRO; PDB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - (salen)MnIII compounds as nonpeptidyl mimics of catalase. Mechanism-based tuning of catalase activity: a theoretical study. AN - 67468366; 15732983 AB - We present the results of the first theoretical investigation of salen-manganese complexes as synthetic catalytic scavengers of hydrogen peroxide molecules that mimic catalase enzymes. Catalase mimics can be used as therapeutic agents against oxidative stress in treatment of many diseases, including Alzheimer's disease, stroke, heart disease, aging, and cancer. A ping-pong mechanism approach has been considered to describe the H2O2 dismutation reaction. The real compounds reacting with a peroxide molecule were utilized in our BP density functional calculations to avoid uncertainties connected with using incomplete models. Part I of the dismutation reaction-converting a peroxide molecule into a water molecule with simultaneous oxidation of the metal atom of the catalyst-can be done quite effectively at the Mn catalytic center. To act as catalytic scavengers of hydrogen peroxide, the oxomanganese salen complexes have to be deoxidized during part II of the dismutation reaction. It has been shown that there are two possible reaction routes for the second part of the dismutation reaction: the top and the side substrate approach routes. Our results suggest that the catalyst could be at least temporarily deactivated (poisoned) in the side approach reaction route due to the formation of a kinetically stable intermediate. Overall, the side approach reaction route for the catalyst recovery is the bottleneck for the whole dismutation process. On the basis of the detailed knowledge of the mode of action of the (salen)MnIII catalase mimics, we suggest and rationalize structural changes of the catalyst that should lead to better therapeutic properties. The available experimental data support our conclusions. Our findings on the reaction dismutation mechanism could be the starting point for further improvement of salen-manganese complexes as synthetic catalytic scavengers of reactive oxygen species. JF - Inorganic chemistry AU - Abashkin, Yuri G AU - Burt, Stanley K AD - Advanced Biomedical Computing Center, SAIC-Frederick, Inc., National Cancer Institute at Frederick, PO Box B, Frederick, Maryland 21702-1201, USA. abashkin@ncifcrf.gov Y1 - 2005/03/07/ PY - 2005 DA - 2005 Mar 07 SP - 1425 EP - 1432 VL - 44 IS - 5 SN - 0020-1669, 0020-1669 KW - Ethylenediamines KW - 0 KW - Organometallic Compounds KW - N,N'-bis(salicylideneamino)ethane-manganese(II) KW - 53177-12-1 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Catalase KW - EC 1.11.1.6 KW - Index Medicus KW - Molecular Structure KW - Models, Molecular KW - Kinetics KW - Molecular Mimicry KW - Models, Chemical KW - Molecular Conformation KW - Catalase -- metabolism KW - Catalase -- chemistry KW - Ethylenediamines -- chemistry KW - Organometallic Compounds -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67468366?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Inorganic+chemistry&rft.atitle=%28salen%29MnIII+compounds+as+nonpeptidyl+mimics+of+catalase.+Mechanism-based+tuning+of+catalase+activity%3A+a+theoretical+study.&rft.au=Abashkin%2C+Yuri+G%3BBurt%2C+Stanley+K&rft.aulast=Abashkin&rft.aufirst=Yuri&rft.date=2005-03-07&rft.volume=44&rft.issue=5&rft.spage=1425&rft.isbn=&rft.btitle=&rft.title=Inorganic+chemistry&rft.issn=00201669&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-17 N1 - Date created - 2005-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Three-dimensional Structure of a Macromolecular Assembly that Regulates Type III Secretion in Yersinia pestis AN - 20816645; 8247600 AB - Yersinia pestis, the causative agent of plague, utilizes a type III secretion system (T3SS) to inject effector proteins directly into the cytosol of mammalian cells where they interfere with signal transduction pathways that regulate actin cytoskeleton dynamics and inflammation, thereby enabling the bacterium to avoid engulfment and destruction by macrophages. Type III secretion normally does not occur in the absence of close contact with eukaryotic cells. Negative regulation is mediated in part by a multiprotein complex that has been proposed to act as a physical impediment to type III secretion by blocking the entrance to the secretion apparatus prior to contact with mammalian cells. This complex is composed of YopN, its heterodimeric secretion chaperone SycN-YscB, and TyeA. Here, we report two crystal structures of YopN in complex with its heterodimeric secretion chaperone SycN-YscB and the co-regulatory protein TyeA, respectively. By merging these two overlapping structures, it was possible to construct a credible theoretical model of the YopN-SycN-YscB-TyeA complex. The modeled assembly features the secretion signaling elements of YopN at one end of an elongated structure and the secretion regulating TyeA binding site at the other. A patch of highly conserved residues on the surface of the C-terminal alpha -helix of TyeA may mediate its interaction with structural components of the secretion apparatus. Conserved arginine residues that reside inside a prominent cavity at the dimer interface of SycN-YscB were mutated in order to investigate whether they play a role in targeting the YopN-chaperone complex to the type III secretion apparatus. One of the mutants exhibited a phenotype that is consistent with this hypothesis. JF - Journal of Molecular Biology AU - Schubot, F D AU - Jackson, M W AU - Penrose, K J AU - Cherry, S AU - Tropea, JE AU - Plano, G V AU - Waugh, D S AD - Center for Cancer Research, National Cancer Institute at Frederick, P.O. Box B, Frederick, MD 21702-1201, USA, waughd@ncifcrf.gov Y1 - 2005/03/04/ PY - 2005 DA - 2005 Mar 04 SP - 1147 EP - 1161 PB - Elsevier Science, P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 346 IS - 4 SN - 0022-2836, 0022-2836 KW - Microbiology Abstracts B: Bacteriology KW - Macrophages KW - Macromolecules KW - Arginine KW - Secretion KW - Yersinia pestis KW - Inflammation KW - Cytoskeleton KW - Mammalian cells KW - Crystal structure KW - Cytosol KW - Actin KW - Chaperones KW - Plague KW - Signal transduction KW - J 02310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20816645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Three-dimensional+Structure+of+a+Macromolecular+Assembly+that+Regulates+Type+III+Secretion+in+Yersinia+pestis&rft.au=Schubot%2C+F+D%3BJackson%2C+M+W%3BPenrose%2C+K+J%3BCherry%2C+S%3BTropea%2C+JE%3BPlano%2C+G+V%3BWaugh%2C+D+S&rft.aulast=Schubot&rft.aufirst=F&rft.date=2005-03-04&rft.volume=346&rft.issue=4&rft.spage=1147&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1016%2Fj.jmb.2004.12.036 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-07-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Macrophages; Macromolecules; Arginine; Secretion; Inflammation; Cytoskeleton; Mammalian cells; Cytosol; Crystal structure; Chaperones; Actin; Plague; Signal transduction; Yersinia pestis DO - http://dx.doi.org/10.1016/j.jmb.2004.12.036 ER - TY - JOUR T1 - Risks and benefits of phase 1 oncology trials, 1991 through 2002. AN - 67484075; 15745980 AB - Previous reviews of phase 1 oncology trials reported a rate of response to treatment of 4 to 6 percent and a toxicity-related death rate of 0.5 percent. These results may not reflect the rates in current phase 1 oncology trials. We reviewed all nonpediatric phase 1 oncology trials sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute between 1991 and 2002. We report the rates of response to treatment, of stable disease, of grade 4 toxic events, and of treatment-related deaths. We analyzed 460 trials involving 11,935 participants, all of whom were assessed for toxicity and 10,402 of whom were assessed for a response to therapy. The overall response rate (i.e., for both complete and partial responses) was 10.6 percent, with considerable variation among trials. "Classic" phase 1 trials of single investigational chemotherapeutic agents represented only 20 percent of the trials and had a response rate of 4.4 percent. Studies that included at least one anticancer agent approved by the Food and Drug Administration constituted 46.3 percent of the trials and had a response rate of 17.8. An additional 34.1 percent of participants had stable disease or a less-than-partial response. The overall rate of death due to toxic events was 0.49 percent. Of 3465 participants for whom data on patient-specific grade 4 toxic events were available, 14.3 percent had had at least one episode of grade 4 toxic events. Overall response rates among phase 1 oncology trials are higher than previously reported, although they have not changed for classic phase 1 trials, and toxicity-related death rates have remained stable. Rates of response and toxicity vary, however, among the various types of phase 1 oncology trials. Copyright 2005 Massachusetts Medical Society. JF - The New England journal of medicine AU - Horstmann, Elizabeth AU - McCabe, Mary S AU - Grochow, Louise AU - Yamamoto, Seiichiro AU - Rubinstein, Larry AU - Budd, Troy AU - Shoemaker, Dale AU - Emanuel, Ezekiel J AU - Grady, Christine AD - Department of Clinical Bioethics, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Md 20892-1156, USA. Y1 - 2005/03/03/ PY - 2005 DA - 2005 Mar 03 SP - 895 EP - 904 VL - 352 IS - 9 KW - Antineoplastic Agents KW - 0 KW - Cancer Vaccines KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Retrospective Studies KW - Outcome Assessment (Health Care) KW - Risk Assessment KW - Genetic Therapy -- adverse effects KW - Cancer Vaccines -- adverse effects KW - Neoplasms -- mortality KW - Clinical Trials, Phase I as Topic KW - Cancer Vaccines -- therapeutic use KW - Neoplasms -- therapy KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67484075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Risks+and+benefits+of+phase+1+oncology+trials%2C+1991+through+2002.&rft.au=Horstmann%2C+Elizabeth%3BMcCabe%2C+Mary+S%3BGrochow%2C+Louise%3BYamamoto%2C+Seiichiro%3BRubinstein%2C+Larry%3BBudd%2C+Troy%3BShoemaker%2C+Dale%3BEmanuel%2C+Ezekiel+J%3BGrady%2C+Christine&rft.aulast=Horstmann&rft.aufirst=Elizabeth&rft.date=2005-03-03&rft.volume=352&rft.issue=9&rft.spage=895&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 - 2005-03-08 N1 - Date created - 2005-03-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 2005 Mar 3;352(9):930-2 [15745986] N Engl J Med. 2005 Jun 9;352(23):2451-3; author reply 2451-3 [15948271] N Engl J Med. 2005 Jun 9;352(23):2451-3; author reply 2451-3 [15948269] N Engl J Med. 2005 Jun 9;352(23):2451-3; author reply 2451-3 [15944433] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor suppressor p53 represses transcription of RECQ4 helicase. AN - 67479548; 15674334 AB - RECQ4 is a member of the RecQ helicase family, which has been implicated in the regulation of DNA replication, recombination and repair. p53 modulates the functions of RecQ helicases including BLM and WRN. In this study, we demonstrate that p53 can regulate the transcription of RECQ4. Using nontransformed, immortalized normal human fibroblasts, we show that p53-dependent downregulation of RECQ4 expression occurred in G1-arrested cells, both in the absence or presence of exogenous DNA damage. Wild-type p53 (but not the tumor-derived mutant forms) repressed RECQ4 promoter activity. The camptothecin or etoposide-dependent p53-mediated repression was attenuated by trichostatin A (TSA), an inhibitor of histone deacetylases (HDACs). Repression of the RECQ4 promoter was accompanied with an increased accumulation of HDAC1, and the loss of SP1 and p53 binding to the promoter. The simultaneous formation of a camptothecin-dependent p53-SP1 complex indicated its occurrence outside of the RECQ4 promoter. These data suggest that p53-mediated repression of RECQ4 transcription during DNA damage results from the modulation of the promoter occupancy of transcription activators and repressors. JF - Oncogene AU - Sengupta, Sagar AU - Shimamoto, Akira AU - Koshiji, Minori AU - Pedeux, Remy AU - Rusin, Marek AU - Spillare, Elisa A AU - Shen, Jiang Cheng AU - Huang, L Eric AU - Lindor, Noralane M AU - Furuichi, Yasuhiro AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2005/03/03/ PY - 2005 DA - 2005 Mar 03 SP - 1738 EP - 1748 VL - 24 IS - 10 SN - 0950-9232, 0950-9232 KW - Hydroxamic Acids KW - 0 KW - Repressor Proteins KW - Tumor Suppressor Protein p53 KW - trichostatin A KW - 3X2S926L3Z KW - Histone Deacetylases KW - EC 3.5.1.98 KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - Index Medicus KW - Promoter Regions, Genetic KW - DNA Damage KW - Cells, Cultured KW - Humans KW - Histone Deacetylases -- metabolism KW - G1 Phase KW - Hydroxamic Acids -- pharmacology KW - Transcriptional Activation KW - Tumor Suppressor Protein p53 -- physiology KW - Repressor Proteins -- physiology KW - DNA Helicases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67479548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+suppressor+p53+represses+transcription+of+RECQ4+helicase.&rft.au=Sengupta%2C+Sagar%3BShimamoto%2C+Akira%3BKoshiji%2C+Minori%3BPedeux%2C+Remy%3BRusin%2C+Marek%3BSpillare%2C+Elisa+A%3BShen%2C+Jiang+Cheng%3BHuang%2C+L+Eric%3BLindor%2C+Noralane+M%3BFuruichi%2C+Yasuhiro%3BHarris%2C+Curtis+C&rft.aulast=Sengupta&rft.aufirst=Sagar&rft.date=2005-03-03&rft.volume=24&rft.issue=10&rft.spage=1738&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-24 N1 - Date created - 2005-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum alpha-Tocopherol and gamma-Tocopherol in Relation to Prostate Cancer Risk in a Prospective Study AN - 20713221; 6190845 AB - The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study demonstrated a 32% reduction in prostate cancer incidence in response to daily alpha-tocopherol supplementation. We examined baseline serum concentrations of alpha-tocopherol and gamma-tocopherol to compare their respective associations with prostate cancer risk. From the ATBC Study cohort of 29 133 Finnish men, 50- 69 years old, we randomly selected 100 incident prostate cancer case patients and matched 200 control subjects. Odds ratios and 95% confidence intervals (CIs) were estimated for the serum tocopherols (measured by high-performance liquid chromatography) using logistic regression models. All P values were two-sided. Odds ratios for the highest versus the lowest tertiles were 0.49 (95% CI = 0.24 to 1.01, P sub(trend) = .05) for alpha-tocopherol and 0.57 (95% CI = 0.31 to 1.06, P sub(trend) = .08) for gamma-tocopherol. Further analyses indicated that the association of high serum tocopherols with low prostate cancer risk was stronger in the alpha-tocopherol-supplemented group than in those not receiving alpha- tocopherol. Participants with higher circulating concentrations of the major vitamin E fractions, alpha-tocopherol and gamma-tocopherol, had similarly lower prostate cancer risk. JF - Journal of the National Cancer Institute AU - Weinstein, Stephanie J AU - Wright, Margaret E AU - Pietinen, Pirjo AU - King, Irena AU - Tan, Carly AU - Taylor, Philip R AU - Virtamo, Jarmo AU - Albanes, Demetrius AD - Division of Cancer Epidemiology and Genetics (SJW, MEW, DA) and Center for Cancer Research (PRT), National Cancer Institute, NIH, DHHS, Bethesda, MD Y1 - 2005/03/02/ PY - 2005 DA - 2005 Mar 02 SP - 396 EP - 399 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 97 IS - 5 SN - 0027-8874, 0027-8874 KW - Risk Abstracts KW - vitamins KW - Liquid chromatography KW - prevention KW - prostate cancer KW - Cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20713221?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Serum+alpha-Tocopherol+and+gamma-Tocopherol+in+Relation+to+Prostate+Cancer+Risk+in+a+Prospective+Study&rft.au=Weinstein%2C+Stephanie+J%3BWright%2C+Margaret+E%3BPietinen%2C+Pirjo%3BKing%2C+Irena%3BTan%2C+Carly%3BTaylor%2C+Philip+R%3BVirtamo%2C+Jarmo%3BAlbanes%2C+Demetrius&rft.aulast=Weinstein&rft.aufirst=Stephanie&rft.date=2005-03-02&rft.volume=97&rft.issue=5&rft.spage=396&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-10-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - vitamins; Liquid chromatography; prevention; prostate cancer; Cancer ER - TY - JOUR T1 - Optimization of acid hydrolysis of sugarcane bagasse and investigations on its fermentability for the production of xylitol by Candida guilliermondii AN - 856760879; 13858279 AB - The dilute-acid hydrolysis of sugarcane bagasse was optimized using a statistical experimental design resulting in hydrolysates containing 57.25 g/L of xylose, which were fermented with a high inoculum concentration (10 g/L of the yeast Candida guilliermondii IM/UFRJ 50088). The addition of urea reduced the time of conversion (t sub(C)) to 75 h (without nitrogen source addition t sub(C)>127 h), and, consequently, improving the rates of xylitol bioproduction. Fermentator experiments, using the optimized conditions, resulted in enhanced conversion rates, reducing t sub(C) to 30 h. The stability of the yeast in the hydrolysate was also verified in a 480-h cultivation. JF - Applied Biochemistry and Biotechnology AU - Fogel, Rafael AU - Garcia, Rafaela Rodrigues AU - Oliveira, Rebeca da Silva AU - Palacio, Denise Neves Menchero AU - Madeira, Luciana da Silva AU - Pereira, Nei AD - Departmento de Engenharia Bioquimica, Escola de Quimica/CT, Universidade Federal do Rio de Janeiro, CEP: 21949-900, RJ, Brazil, nei@eq.ufrj.br Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 741 EP - 752 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 122 IS - 1-3 SN - 0273-2289, 0273-2289 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Biotechnology and Bioengineering Abstracts KW - Bagasse KW - Statistics KW - Xylose KW - Nitrogen sources KW - Xylitol KW - Inoculum KW - Urea KW - Candida guilliermondii KW - Hydrolysis KW - Hydrolysates KW - A 01310:Products of Microorganisms KW - W 30945:Fermentation & Cell Culture KW - K 03320:Cell Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/856760879?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+Biochemistry+and+Biotechnology&rft.atitle=Optimization+of+acid+hydrolysis+of+sugarcane+bagasse+and+investigations+on+its+fermentability+for+the+production+of+xylitol+by+Candida+guilliermondii&rft.au=Fogel%2C+Rafael%3BGarcia%2C+Rafaela+Rodrigues%3BOliveira%2C+Rebeca+da+Silva%3BPalacio%2C+Denise+Neves+Menchero%3BMadeira%2C+Luciana+da+Silva%3BPereira%2C+Nei&rft.aulast=Fogel&rft.aufirst=Rafael&rft.date=2005-03-01&rft.volume=122&rft.issue=1-3&rft.spage=741&rft.isbn=&rft.btitle=&rft.title=Applied+Biochemistry+and+Biotechnology&rft.issn=02732289&rft_id=info:doi/10.1385%2FABAB%3A122%3A1-3%3A0741 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-03-01 N1 - Last updated - 2013-12-04 N1 - SubjectsTermNotLitGenreText - Bagasse; Xylose; Statistics; Nitrogen sources; Xylitol; Inoculum; Urea; Hydrolysis; Hydrolysates; Candida guilliermondii DO - http://dx.doi.org/10.1385/ABAB:122:1-3:0741 ER - TY - JOUR T1 - Motor training as treatment in focal hand dystonia. AN - 85380899; pmid-15486996 AB - Focal hand dystonia may arise as a result of aberrant plasticity from excessive repetitive use. Improvement might be possible with appropriate motor training. Focusing on trying to decrease abnormal overflow of movement to fingers not involved in a task, we developed a motor training program for individualized finger movements. Ten patients with writer's cramp participated in the motor training program. Evaluation was done with the Fahn dystonia scale, kinematic analysis of handwriting, transcranial magnetic stimulation (TMS), and electroencephalography (EEG). Clinical improvement of dystonia was significant using the Fahn dystonia scale, and 6 patients reported an improvement in writing. The handwriting analysis showed a trend for improvement after training in simple exercises. There were no changes in cortical excitability measured by TMS and EEG. Whereas this method of motor training for 4 weeks led to mild subjective improvement and some improvement in handwriting, it is not sufficient to reverse motor cortex abnormalities measured by TMS and EEG.2004 Movement Disorder Society. JF - Movement disorders : official journal of the Movement Disorder Society AU - Zeuner, Kirsten E AU - Shill, Holly A AU - Sohn, Young H AU - Molloy, Fiona M AU - Thornton, Bonnie C AU - Dambrosia, James M AU - Hallett, Mark AD - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1428, USA. Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 335 EP - 341 VL - 20 IS - 3 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Cerebral Cortex: physiology KW - Dystonia: diagnosis KW - *Dystonia: physiopathology KW - *Dystonia: therapy KW - Dystonic Disorders: physiopathology KW - Dystonic Disorders: therapy KW - Electroencephalography KW - Electromyography: instrumentation KW - Evoked Potentials, Motor: physiology KW - Fingers: physiology KW - *Hand: physiopathology KW - Humans KW - *Magnetics: instrumentation KW - Middle Aged KW - Severity of Illness Index KW - *Teaching: methods KW - Wrist: physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85380899?accountid=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=Motor+training+as+treatment+in+focal+hand+dystonia.&rft.au=Zeuner%2C+Kirsten+E%3BShill%2C+Holly+A%3BSohn%2C+Young+H%3BMolloy%2C+Fiona+M%3BThornton%2C+Bonnie+C%3BDambrosia%2C+James+M%3BHallett%2C+Mark&rft.aulast=Zeuner&rft.aufirst=Kirsten&rft.date=2005-03-01&rft.volume=20&rft.issue=3&rft.spage=335&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 - High-frequency gamma-band activity in the basal temporal cortex during picture-naming and lexical-decision tasks. AN - 85298075; pmid-15800183 AB - Gamma-band activity (GBA) in electroencephalograms (EEGs) has been shown to reflect various cognitive processes. GBA has typically been recorded in the 30-60 Hz range in scalp EEGs. Recently, task-related "high GBA" (HGBA) with frequencies up to 100 Hz has been observed in studies with invasive electrocorticograms (ECoGs). In the present study, we recorded ECoGs from the bilateral basal temporal cortices in a patient with epilepsy and evaluated the task-related HGBA (most prominently in the 80-120 Hz range) accompanying picture-naming and lexical-decision tasks. We examined picture naming using two categories (line drawings of animals and tools). The lexical-decision task was performed using words and pseudowords of two distinct Japanese writing forms, kanji (morphograms) and kana (syllabograms). Task-related HGBA was observed bilaterally during the naming task. Recordings from some electrodes revealed significant differences in HGBA between animal and tool pictures. In contrast to the naming task, there was apparent left dominance in the lexical-decision task. Furthermore, significant differences in HGBA were observed between the Japanese kanji and kana words and between the kanji words and kanji pseudowords. A number of differences in the HGBA observed in the recordings from the basal temporal area were consistent with previous findings from neuroimaging and patient studies and suggest that HGBA is a good correlate of visual cognitive functions. JF - The Journal of Neuroscience AU - Tanji Kazuyo AU - Suzuki, Kyoko AU - Delorme Arnaud AU - Shamoto Hiroshi AU - Nakasato Nobukazu AD - Graduate School of International Cultural Studies, Tohoku University, Sendai 980-8576, Japan. tanjik@mail.nih.gov PY - 2005 SP - 3287 EP - 3293 VL - 25 IS - 13 SN - 0270-6474, 0270-6474 KW - Humans KW - Electroencephalography KW - Decision Making KW - Research Support, Non-U.S. Gov't KW - Photic Stimulation KW - Brain Mapping KW - Comparative Study KW - Evoked Potentials KW - Pattern Recognition, Visual KW - Adult KW - Acoustic Stimulation KW - Laterality KW - Time Factors KW - Male KW - Epilepsy, Temporal Lobe KW - Reaction Time KW - Reading KW - Language KW - High-Frequency Ventilation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85298075?accountid=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=High-frequency+gamma-band+activity+in+the+basal+temporal+cortex+during+picture-naming+and+lexical-decision+tasks.&rft.au=Tanji+Kazuyo%3BSuzuki%2C+Kyoko%3BDelorme+Arnaud%3BShamoto+Hiroshi%3BNakasato+Nobukazu&rft.aulast=Tanji+Kazuyo&rft.aufirst=&rft.date=2005-03-01&rft.volume=25&rft.issue=13&rft.spage=3287&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 - Evaluation of hybridization conditions for spotted oligonucleotide-based DNA microarrays AN - 839703816; 13860126 AB - We compared different hybridization conditions of oligonucleotide-based DNA microarray to acquire optimized and reliable microarray data. Several parameters were evaluated at different hybridization conditions, including signal-to-background (S:B) ratios, signal dynamic range, usable spots, and reproducibility. Statistical analysis showed that better results were obtained when spotted, presynthesized long oligonucleotide arrays were blocked with succinic anhydride and hybridized at 42C in the presence of 50% formamide. JF - Molecular Biotechnology AU - Tsai, Mong-Hsun AU - Yan, Hailing AU - Chen, Xi AU - Chandramouli, GVR AU - Zhao, Shuping AU - Coffin, Deborah AU - Coleman, CNorman AU - Mitchell, James B AU - Chuang, Eric Y AD - Radiation Oncology Sciences Program, Radiation Oncology Branch, Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 8717 Grovemont Cr., Room 109J, 20878, Gaithersburg, MD, chuange@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 221 EP - 224 PB - Humana Press Inc., 999 Riverview Dr., Ste. 208 Totowa NJ 07512 USA VL - 29 IS - 3 SN - 1073-6085, 1073-6085 KW - Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Data processing KW - Statistical analysis KW - DNA microarrays KW - W 30910:Imaging KW - N 14810:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/839703816?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evaluation+of+hybridization+conditions+for+spotted+oligonucleotide-based+DNA+microarrays&rft.au=Tsai%2C+Mong-Hsun%3BYan%2C+Hailing%3BChen%2C+Xi%3BChandramouli%2C+GVR%3BZhao%2C+Shuping%3BCoffin%2C+Deborah%3BColeman%2C+CNorman%3BMitchell%2C+James+B%3BChuang%2C+Eric+Y&rft.aulast=Tsai&rft.aufirst=Mong-Hsun&rft.date=2005-03-01&rft.volume=29&rft.issue=3&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Molecular+Biotechnology&rft.issn=10736085&rft_id=info:doi/10.1385%2FMB%3A29%3A3%3A221 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-01-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Data processing; Statistical analysis; DNA microarrays DO - http://dx.doi.org/10.1385/MB:29:3:221 ER - TY - JOUR T1 - Management of neurodegenerative disorders: Parkinson's disease and Alzheimer's disease. AN - 68600798; 16173294 AB - Neurodegenerative disorders result from premature progressive degeneration of specific neurons, and manifest as diseases or syndromes with varied combinations of cognitive, motor, sensory and autonomic dysfunctions. The management involves pharmacotherapy as well as non-pharmacological measures and also to lessen the burden of the care-givers. The medications available for medical treatment are: Levodopa, dopamine agonists, amantadine, anticholinergics, enzyme inhibitors, etc. Advanced Parkinson's disease is concerned with management of motor complications and non-motor complications. Recently surgical treatment is a great option for managing motor complication. Orthostatic hypotension, gait distiurbances, emotional and psychiatric problems, sleep disturbances can be managed and had been discussed in brief. Currently there is no medication available for the cure of Alzheimer's disease. The specific medications claimed to improve patient's well being and cognition include cholinesterase inhibitors, N-methyl-D-aspartate receptor antagonist, anti-oxidants, and anti-amyloid therapy. While medical and surgical treatments for Parkinson's disease have revolutionised the management, still drug therapy for Alzheimer's disease is dismal. JF - Journal of the Indian Medical Association AU - Pal, P K AU - Netravathi, M AD - Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore 560029. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 168 EP - 70, 172, 174-6 VL - 103 IS - 3 SN - 0019-5847, 0019-5847 KW - Antiparkinson Agents KW - 0 KW - Nootropic Agents KW - Index Medicus KW - Antiparkinson Agents -- adverse effects KW - Physical Therapy Modalities KW - Humans KW - Antiparkinson Agents -- therapeutic use KW - Nootropic Agents -- therapeutic use KW - Antiparkinson Agents -- pharmacology KW - Nootropic Agents -- pharmacology KW - Nootropic Agents -- adverse effects KW - Alzheimer Disease -- complications KW - Alzheimer Disease -- drug therapy KW - Alzheimer Disease -- therapy KW - Parkinson Disease -- complications KW - Parkinson Disease -- drug therapy KW - Parkinson Disease -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68600798?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+Indian+Medical+Association&rft.atitle=Management+of+neurodegenerative+disorders%3A+Parkinson%27s+disease+and+Alzheimer%27s+disease.&rft.au=Pal%2C+P+K%3BNetravathi%2C+M&rft.aulast=Pal&rft.aufirst=P&rft.date=2005-03-01&rft.volume=103&rft.issue=3&rft.spage=168&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Indian+Medical+Association&rft.issn=00195847&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-17 N1 - Date created - 2005-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupation and lung cancer risk in Leningrad Province, Russia. AN - 68009877; 16001514 AB - To investigate the association between occupation and lung cancer risk in Leningrad Province, Russia, we identified 540 pathologically diagnosed lung cancer cases (474 males and 66 females) and 582 controls (453 males and 129 females) from the 1993-1998 autopsy records of the 88 state hospitals of the Province. Lifetime occupational histories were obtained from personal records coded according to the standard Russian occupational classification system. Lung cancer risk was increased in workers in the manufacturing industry, particularly in the food industry and wholesale/retail trade and in the miscellaneous manufacturing industry. An increased risk was also found in subjects employed in chemical and metal production for 10 years or more. When we considered the association between specific occupations and lung cancer, waste incineration operators and loaders exhibited an excess risk that increased with employment duration. The present study, which is the first to evaluate the risk of lung cancer by occupation in Russia, suggests the presence in Leningrad Province of exposure in the workplace to lung carcinogens that require further characterization to develop targeted and effective preventive measures. JF - La Medicina del lavoro AU - Baccarelli, A AU - Tretiakova, Maria AU - Gorbanev, S AU - Lomtev, A AU - Klimkina, Irina AU - Tchibissov, V AU - Averkina, Olga AU - Dosemeci, M AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. PY - 2005 SP - 142 EP - 154 VL - 96 IS - 2 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Humans KW - Aged KW - Forms and Records Control KW - Smoking -- epidemiology KW - Cause of Death KW - Russia -- epidemiology KW - Risk KW - Aged, 80 and over KW - Agricultural Workers' Diseases -- epidemiology KW - Adult KW - Case-Control Studies KW - Food Industry KW - Administrative Personnel KW - Middle Aged KW - Male KW - Chemical Industry KW - Female KW - Industry KW - Lung Neoplasms -- epidemiology KW - Lung Neoplasms -- mortality KW - Occupations -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68009877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Focal+adhesion+kinase+as+a+potential+target+in+arsenic+toxicity.&rft.au=Liu%2C+Jie%3BWaalkes%2C+Michael&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2005-04-01&rft.volume=84&rft.issue=2&rft.spage=212&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 - 2005-09-20 N1 - Date created - 2005-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A potential role for vascular endothelial growth factor-D as an autocrine growth factor for human breast carcinoma cells. AN - 67790614; 15868899 AB - Vascular endothelial growth factor-D (VEGF-D) binds and activates vascular endothelial growth factor receptor-2 (VEGFR-2), which signals for angiogenesis, and VEGFR-3, which signals for lymphangiogenesis. Besides endothelial cells, VEGFR-2 has been detected on malignant cells, including human breast carcinoma cells. It was examined if ectopic expression of human VEGF-D affected growth of breast carcinoma cell lines in vitro and in vivo. VEGF-D overexpressing clonal MCF-7 and MDA-MB-231 cell lines displayed increased proliferative activities and upregulation of cyclins A, D1 and D3, compared to the vector control. Following subcutaneous inoculation of the MDA-MB-231 cells into nude mice, growth of the VEGF-D overexpressing cells was greatly accelerated. The tumor weight gain was accompanied by increased proliferative activity, cyclin A expression and microvascular density. These findings suggest that VEGF-D functions both as an autocrine growth factor and a stimulator of angiogenesis in breast cancer. JF - Anticancer research AU - Akahane, Manabu AU - Akahane, Takemi AU - Shah, Amy AU - Okajima, Eijiro AU - Thorgeirsson, Unnur P AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD 20892-4255, USA. PY - 2005 SP - 701 EP - 707 VL - 25 IS - 2A SN - 0250-7005, 0250-7005 KW - CCND3 protein, human KW - 0 KW - Ccnd3 protein, mouse KW - Cyclin A KW - Cyclin D3 KW - Cyclins KW - DNA, Complementary KW - Vascular Endothelial Growth Factor D KW - Cyclin D1 KW - 136601-57-5 KW - Index Medicus KW - Animals KW - Cyclin A -- genetics KW - Cyclins -- biosynthesis KW - DNA, Complementary -- genetics KW - Cell Growth Processes -- physiology KW - Humans KW - Neovascularization, Pathologic -- metabolism KW - Mice, Nude KW - Mice KW - Cell Line, Tumor KW - Cyclin D1 -- biosynthesis KW - Cyclin D1 -- genetics KW - Neovascularization, Pathologic -- pathology KW - Cyclin A -- biosynthesis KW - Blotting, Western KW - Transfection KW - Enzyme-Linked Immunosorbent Assay KW - Up-Regulation KW - Female KW - Cyclins -- genetics KW - Vascular Endothelial Growth Factor D -- physiology KW - Breast Neoplasms -- genetics KW - Carcinoma -- pathology KW - Carcinoma -- blood supply KW - Breast Neoplasms -- pathology KW - Vascular Endothelial Growth Factor D -- genetics KW - Vascular Endothelial Growth Factor D -- biosynthesis KW - Breast Neoplasms -- metabolism KW - Carcinoma -- metabolism KW - Breast Neoplasms -- blood supply KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67790614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+potential+role+for+vascular+endothelial+growth+factor-D+as+an+autocrine+growth+factor+for+human+breast+carcinoma+cells.&rft.au=Akahane%2C+Manabu%3BAkahane%2C+Takemi%3BShah%2C+Amy%3BOkajima%2C+Eijiro%3BThorgeirsson%2C+Unnur+P&rft.aulast=Akahane&rft.aufirst=Manabu&rft.date=2005-03-01&rft.volume=25&rft.issue=2A&rft.spage=701&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 - 2005-06-09 N1 - Date created - 2005-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Primary chemotherapy with epirubicin and vinorelbine in women with locally advanced breast cancer. AN - 67781614; 15865089 AB - To assess the activity and toxicity of primary chemotherapy with epirubicin (60 mg/m2 every other week) and vinorelbine (25 mg/m2, weekly) plus granulocyte colony-stimulating factor (G-CSF) for 12 weeks, in patients with locally advanced breast cancer in a multicenter setting. Patients with stage IIIA or IIIB breast cancer, not older than 70, were eligible. A two-stage phase II design was applied. Response was assessed clinically, instrumentally and pathologically. Out of 48 enrolled patients, 87.5% received all planned cycles, with a median dose-intensity of 30 mg/m2/week for epirubicin and 23.8 mg/m2/week for vinorelbine. A clinical or instrumental objective response was reached in 42 patients (87.5%, exact 95% CI: 74.7-95.3); significant downstaging was reached in all but one patient; 6 cases had a pathological complete response in the breast, and 2 cases in the lymph nodes too (pathological complete response rate 4.2%, exact 95% CI: 0.5-14.2); a further 2 patients had only microscopic cancer foci at pathological examination of the breast. Radiological tests underestimated the treatment effect on the breast. Toxicity was mild, neutropenia being the most frequent (grade 3-4 in 47% of patients), but never complicated with fever or sepsis. Mild constipation (< or =grade 2) occurred in 35% of patients. Moderate to severe asthenia occurred in 12% of 6 patients. No cardiac toxicity was reported. At 3 years, disease-free survival was 68% and overall survival 81%. Primary chemotherapy with epirubicin every other week, weekly vinorelbine and G-CSF support is highly active and well tolerated in patients with locally advanced breast cancer. JF - Anticancer research AU - Nisticò, Cecilia AU - De Matteis, Andrea AU - Rossi, Emanuela AU - Carnino, Flavio AU - Valenza, Roberto AU - Agostara, Biagio AU - Bria, Emilio AU - Farris, Antonio AU - Cremonesi, Marco AU - D'Ottavio, Anna Maria AU - Vaccaro, Angela AU - Garufi, Carlo AU - Giunta, Salvatore AU - Botti, Claudio AU - Perrone, Francesco AU - Terzoli, Edmondo AD - Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy. cnistico@ifo.it PY - 2005 SP - 1343 EP - 1348 VL - 25 IS - 2B SN - 0250-7005, 0250-7005 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Epirubicin KW - 3Z8479ZZ5X KW - Vinblastine KW - 5V9KLZ54CY KW - vinorelbine KW - Q6C979R91Y KW - Index Medicus KW - Disease-Free Survival KW - Survival Rate KW - Humans KW - Adult KW - Neutropenia -- chemically induced KW - Aged KW - Middle Aged KW - Mastectomy KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Female KW - Breast Neoplasms -- drug therapy KW - Vinblastine -- analogs & derivatives KW - Vinblastine -- administration & dosage KW - Epirubicin -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Breast Neoplasms -- surgery KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67781614?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Primary+chemotherapy+with+epirubicin+and+vinorelbine+in+women+with+locally+advanced+breast+cancer.&rft.au=Nistic%C3%B2%2C+Cecilia%3BDe+Matteis%2C+Andrea%3BRossi%2C+Emanuela%3BCarnino%2C+Flavio%3BValenza%2C+Roberto%3BAgostara%2C+Biagio%3BBria%2C+Emilio%3BFarris%2C+Antonio%3BCremonesi%2C+Marco%3BD%27Ottavio%2C+Anna+Maria%3BVaccaro%2C+Angela%3BGarufi%2C+Carlo%3BGiunta%2C+Salvatore%3BBotti%2C+Claudio%3BPerrone%2C+Francesco%3BTerzoli%2C+Edmondo&rft.aulast=Nistic%C3%B2&rft.aufirst=Cecilia&rft.date=2005-03-01&rft.volume=25&rft.issue=2B&rft.spage=1343&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 - 2005-05-10 N1 - Date created - 2005-05-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Zidovudine induces S-phase arrest and cell cycle gene expression changes in human cells. AN - 67765616; 15784690 AB - Antiretroviral therapy for the human immunodeficiency virus-1 (HIV-1) typically includes two nucleoside reverse transcriptase inhibitors (NRTIs). 3'-Azido-3'-deoxythymidine (AZT, Zidovudine) plus 2'-deoxy-3'-thiacytidine (3TC, Lamivudine) is a combination that is used frequently. The NRTIs are mutagenic nucleoside analogs that become incorporated into DNA and terminate replication. We therefore hypothesized that exposure to this class of drug may alter cell cycle parameters. We used flow cytometry to examine the cell cycle in human epithelioid carcinoma (HeLa) cells exposed to AZT and 3TC alone, as well as a series of AZT/3TC dose combinations: (A) 125.0 microM AZT/12.5 microM 3TC; (B) 250.0 microM AZT/25.0 microM 3TC; and (C) 500 microM AZT/50 microM 3TC. At 24 h, at all doses, there was a good cell viability (>/=68%), and incorporation of AZT into nuclear DNA. Using flow cytometry, a dose-related increase in the percentage of cells in S phase, from 9.5% with no drug, to 36.0% with dose C, was observed in cells exposed for 24 h (P = 0.001, ANOVA). A concomitant decrease in the percentage of cells in G(1) phase, from 82.6% with no drug to 58.5% with dose C, was observed in cells exposed for 24 h (P = 0.017, ANOVA). A similar S phase arrest was seen in cells exposed to 125, 250 and 500 microM AZT alone, but there was no S phase alteration with 50 microM 3TC alone, suggesting that AZT is responsible for the accumulation of cells in S phase. To elucidate the accumulation of cells in S phase and explore the cell cycle gene expression changes induced by AZT and 3TC, we used c-DNA microarray, Cell Cycle Super Array and real-time PCR. There was a strong upregulation of the DNA damage-inducible transcript 3 (DDIT3 or GADD153) in NRTI-exposed cells. In addition, AZT induced an upregulation of cyclin D1 accompanied by a downregulation of the cyclin D1-associated inhibitors P18 and P57, and the G(1)-S check point gene P21, the net effect of which would be to foster a cell progression into S phase. Cyclin A2 was down-regulated in cells exposed to AZT, suggesting a block in S-G(2)-M progression that would also be consistent with the accumulation of cells in S phase. Overall, the study demonstrates that AZT, but not 3TC, causes an arrest of cells in S phase with a consistent alteration in the expression of several cell cycle genes. JF - Mutagenesis AU - Olivero, Ofelia A AU - Tejera, Agueda M AU - Fernandez, Juan J AU - Taylor, Barbara J AU - Das, Shreyasi AU - Divi, Rao L AU - Poirier, Miriam C AD - Carcinogen-DNA Interactions Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. oliveroo@exchange.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 139 EP - 146 VL - 20 IS - 2 SN - 0267-8357, 0267-8357 KW - Anti-HIV Agents KW - 0 KW - DNA Adducts KW - Mutagens KW - Reverse Transcriptase Inhibitors KW - Lamivudine KW - 2T8Q726O95 KW - Zidovudine KW - 4B9XT59T7S KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Gene Expression -- drug effects KW - Reverse Transcriptase Inhibitors -- administration & dosage KW - Oligonucleotide Array Sequence Analysis KW - HeLa Cells KW - Humans KW - Mutagens -- toxicity KW - Reverse Transcriptase Inhibitors -- toxicity KW - Mutagens -- administration & dosage KW - DNA Adducts -- metabolism KW - Lamivudine -- toxicity KW - Polymerase Chain Reaction KW - Base Sequence KW - DNA -- genetics KW - Lamivudine -- administration & dosage KW - Anti-HIV Agents -- toxicity KW - S Phase -- drug effects KW - Zidovudine -- toxicity KW - Anti-HIV Agents -- administration & dosage KW - Zidovudine -- administration & dosage KW - Cell Cycle -- genetics KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67765616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Zidovudine+induces+S-phase+arrest+and+cell+cycle+gene+expression+changes+in+human+cells.&rft.au=Olivero%2C+Ofelia+A%3BTejera%2C+Agueda+M%3BFernandez%2C+Juan+J%3BTaylor%2C+Barbara+J%3BDas%2C+Shreyasi%3BDivi%2C+Rao+L%3BPoirier%2C+Miriam+C&rft.aulast=Olivero&rft.aufirst=Ofelia&rft.date=2005-03-01&rft.volume=20&rft.issue=2&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-08 N1 - Date created - 2005-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immune reconstitution following hematopoietic progenitor cell transplantation: challenges for the future. AN - 67710792; 15812532 AB - Successful hematopoietic progenitor cell transplantation requires rapid and complete transfer of the donor hematopoietic and immune systems to the host. Whereas the uncontrolled transfer of a nontolerant donor immune system results in GVHD in many cases, strategies which diminish GVHD also diminish immune reconstitution. Thus, the reliable, rapid and safe transfer of immunity from donor to host remains a major challenge for the field. Advances in the understanding of the biology of immune reconstitution have elucidated that thymic-dependent immune reconstitution can restore global immunity, but is especially vulnerable to toxicities associated with transplant. Alternatively, homeostatic peripheral expansion can be exploited for targeted immunity toward pathogens and tumors, but is difficult to manipulate without exacerbating GVHD risk. New translatable strategies are needed to safely augment one or both of these pathways in the setting of allogeneic hematopoietic progenitor cell transplantation. JF - Bone marrow transplantation AU - Fry, T J AU - Mackall, C L AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - S53 EP - S57 VL - 35 Suppl 1 SN - 0268-3369, 0268-3369 KW - Index Medicus KW - Animals KW - Humans KW - Graft Survival KW - Transplantation, Autologous KW - Graft vs Host Disease -- prevention & control KW - Hematopoietic Stem Cell Transplantation -- trends KW - Recovery of Function KW - Hematopoietic Stem Cell Transplantation -- methods KW - Immune System UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67710792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=Green+tea+consumption%2C+genetic+susceptibility%2C+PAH-rich+smoky+coal%2C+and+the+risk+of+lung+cancer&rft.au=Bonner%2C+M+R%3BRothman%2C+N%3BMumford%2C+J+L%3BHe%2C+X%3BShen%2C+M%3BWelch%2C+R%3BYeager%2C+M%3BChanock%2C+S%3BCaporaso%2C+N%3BLan%2C+Q&rft.aulast=Bonner&rft.aufirst=M&rft.date=2005-04-04&rft.volume=582&rft.issue=1-2&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&rft_id=info:doi/10.1016%2Fj.mrgentox.2004.12.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-30 N1 - Date created - 2005-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Influence of functional group substitutions on the carcinogenicity of anthraquinone in rats and mice: analysis of long-term bioassays by the National Cancer Institute and the National Toxicology Program. AN - 67700199; 15804751 AB - The carcinogenic activities of anthraquinone and six derivatives were compared and contrasted. Studies included representatives of amino, alkyl, nitro, hydroxy, or halogen-containing anthraquinones, with the purpose of uncovering general structure-activity relationships. Anthraquinone, 2-aminoanthraquinone, 1-amino-2-methylanthraquinone, 2-methyl-1-nitroanthraquinone,1-amino-2,4-dibromoanthraquinone, 1,4,5,8-tetraaminoanthraquinone, and 1,3,8-trihydroxy-6-methylanthraquinone (of varying purities) were administered via feed to Fischer 344/N rats and B6C3F, mice. In rats, anthraquinone induced tumors in the liver, kidney, and urinary bladder. A 2-amino substitution narrowed the carcinogenicity to the liver, while multiple amino substitutions led to a carcinogenic response in the urinary bladder alone. A methyl substitution ortho to a 1-aminogroup preserved the hepatic and renal neoplasms seen with the parent anthraquinone, but did not induce urinary bladder tumors; amino or bromo substitutions para to a 1-amino group were related to urinary bladder neoplasms. The intestine may have been a target organ for bromine-substituted anthraquinones. The presence of a nitro group altered the targets of carcinogenicity, and skin tumors may have been associated with this particular functional group in both rats and mice. Over-all for mice, the findings were somewhat different and limited by the small number of common target organs. The parent anthraquinone was clearly carcinogenic only to the liver. There were no other effects of single amino substitutions, in the presence or absence of an additional methyl group, on the carcinogenicity or the site of carcinogenesis of anthraquinone in mice. Multiple amino substitutions diminished, while bromine substitutions enhanced the carcinogenicity induced by anthraquinone and extended the target organs to include forestomach and lung. JF - Journal of toxicology and environmental health. Part B, Critical reviews AU - Doi, Adriana M AU - Irwin, Richard D AU - Bucher, John R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. doi@niehs.nih.gov PY - 2005 SP - 109 EP - 126 VL - 8 IS - 2 SN - 1093-7404, 1093-7404 KW - Anthraquinones KW - 0 KW - Carcinogens KW - Index Medicus KW - Rats KW - Animals KW - Biological Assay KW - Mice KW - Structure-Activity Relationship KW - Neoplasms, Experimental -- chemically induced KW - Carcinogens -- toxicity KW - Anthraquinones -- metabolism KW - Anthraquinones -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67700199?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+B%2C+Critical+reviews&rft.atitle=Influence+of+functional+group+substitutions+on+the+carcinogenicity+of+anthraquinone+in+rats+and+mice%3A+analysis+of+long-term+bioassays+by+the+National+Cancer+Institute+and+the+National+Toxicology+Program.&rft.au=Doi%2C+Adriana+M%3BIrwin%2C+Richard+D%3BBucher%2C+John+R&rft.aulast=Doi&rft.aufirst=Adriana&rft.date=2005-03-01&rft.volume=8&rft.issue=2&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+B%2C+Critical+reviews&rft.issn=10937404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-28 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterologous protein production from the inducible MET25 promoter in Saccharomyces cerevisiae. AN - 67573523; 15801808 AB - Heterologous protein production late in Saccharomyces cerevisiae fermentations is often desirable because it may help avoid the unintentional selection of more rapidly growing, non-protein-expressing cells or allow for the expression of toxic proteins. Here, we describe the use of the MET25 promoter for the production of human serum albumin (HSA) and HSA-fusion proteins in S. cerevisiae. In media lacking methionine, the MET25 promoter yielded high expression levels of HSA and HSA fused to human glucagon, human growth hormone, human interferon alpha, and human interleukin-2. More importantly, we have shown that this system can be used to delay heterologous protein production until late log phase of the growth of the culture and does not require the addition of an exogenous inducer. JF - Biotechnology progress AU - Solow, Steven P AU - Sengbusch, Jennifer AU - Laird, Michael W AD - Human Genome Sciences, Inc., Rockville, Maryland 20850, USA. solow@ncbi.nlm.nih.gov PY - 2005 SP - 617 EP - 620 VL - 21 IS - 2 SN - 8756-7938, 8756-7938 KW - Recombinant Fusion Proteins KW - 0 KW - Saccharomyces cerevisiae Proteins KW - Methionine KW - AE28F7PNPL KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Recombinant Fusion Proteins -- biosynthesis KW - Electrophoresis, Polyacrylamide Gel KW - Recombinant Fusion Proteins -- genetics KW - Methionine -- metabolism KW - Plasmids KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Promoter Regions, Genetic KW - Saccharomyces cerevisiae Proteins -- genetics KW - Saccharomyces cerevisiae Proteins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67573523?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biotechnology+progress&rft.atitle=Heterologous+protein+production+from+the+inducible+MET25+promoter+in+Saccharomyces+cerevisiae.&rft.au=Solow%2C+Steven+P%3BSengbusch%2C+Jennifer%3BLaird%2C+Michael+W&rft.aulast=Solow&rft.aufirst=Steven&rft.date=2005-03-01&rft.volume=21&rft.issue=2&rft.spage=617&rft.isbn=&rft.btitle=&rft.title=Biotechnology+progress&rft.issn=87567938&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-06 N1 - Date created - 2005-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of target genes induced by IL-13 cytotoxin in human glioblastoma cells. AN - 67569226; 15803373 AB - IL-13 cytotoxin comprised of IL-13 and a mutated form of Pseudomonas exotoxin (fusion protein termed IL-13-PE38QQR) has been shown to inhibit protein synthesis leading to necrotic and apoptotic cell death in glioblastoma cells that express high levels of interleukin-13 receptors (IL-13R). To identify target genes of cell death and other cellular genes with IL-13 receptors in glioblastoma cells, we utilized the cDNA microarrays to analyze global gene expression profiles after IL-13 cytotoxin and IL-13 treatment. IL-13 cytotoxin mediated cytotoxicity to U251 cells in a dose-dependent manner. Hierarchical cluster analysis of differentially expressed genes in U251 glioma cells at different time points after IL-13 cytotoxin treatment showed three major groups, each representing a specific expression pattern. Randomly selected differentially expressed genes from each group were confirmed by RT-PCR analysis. Most down-regulated genes belong to cell adhesion, motility, angiogenesis, DNA repair, and metabolic pathways. While up-regulated genes belong to cell cycle arrest, apoptosis, signaling and various metabolic pathways. Unexpectedly, at early time points, both IL-13 and IL-13 cytotoxin induced several genes belonging to different pathways most notably IL-8, DIO2, END1, and ALDH1A3 indicating that these genes are early response genes and their products may be associated with IL-13R. In addition, IL-13 cytotoxin induced IL-13Ralpha2 mRNA expression during the treatment in glioma cells. Our results indicate that novel cellular genes are involved with IL-13 receptors and that IL-13 cytotoxin induced cell death involves various target genes in human glioblastoma cells. On going studies will determine the role of associated genes and their products in the IL-13R functions in glioma cells. JF - Journal of neuro-oncology AU - Han, Jing AU - Yang, Liming AU - Puri, Raj K AD - Laboratory of Molecular Tumor Biology, CBER/NCI Genomics Program, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, CBER/FDA, NIH, Bethesda, MD 20892, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 35 EP - 46 VL - 72 IS - 1 SN - 0167-594X, 0167-594X KW - Antineoplastic Agents KW - 0 KW - Bacterial Toxins KW - Cytotoxins KW - Exotoxins KW - IL13-PE38QQR KW - IL13RA1 protein, human KW - Immunotoxins KW - Interleukin-13 KW - Interleukin-13 Receptor alpha1 Subunit KW - Neoplasm Proteins KW - Receptors, Interleukin KW - Receptors, Interleukin-13 KW - Recombinant Fusion Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Receptors, Interleukin -- metabolism KW - Gene Silencing KW - Dose-Response Relationship, Drug KW - Humans KW - Apoptosis -- physiology KW - Bacterial Toxins -- pharmacology KW - Cell Line, Tumor KW - Cytotoxins -- pharmacology KW - ADP Ribose Transferases -- pharmacology KW - Cell Death -- drug effects KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Virulence Factors -- pharmacology KW - Gene Expression Profiling KW - Apoptosis -- drug effects KW - Receptors, Interleukin -- drug effects KW - Antineoplastic Agents -- pharmacology KW - Cluster Analysis KW - Neoplasm Proteins -- drug effects KW - Glioblastoma -- genetics KW - Exotoxins -- pharmacology KW - Brain Neoplasms -- drug therapy KW - Brain Neoplasms -- genetics KW - Glioblastoma -- drug therapy KW - Immunotoxins -- pharmacology KW - Neoplasm Proteins -- metabolism KW - Interleukin-13 -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67569226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Modeling+spontaneous+activity+in+the+developing+spinal+cord+using+activity-dependent+variations+of+intracellular+chloride.&rft.au=Marchetti%2C+Cristina%3BTabak%2C+Joel%3BChub%2C+Nikolai%3BO%27Donovan%2C+Michael+J%3BRinzel%2C+John&rft.aulast=Marchetti&rft.aufirst=Cristina&rft.date=2005-04-06&rft.volume=25&rft.issue=14&rft.spage=3601&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 - 2005-07-08 N1 - Date created - 2005-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The fetal basis of adult disease: Role of environmental exposures--introduction. AN - 67566105; 15751038 JF - Birth defects research. Part A, Clinical and molecular teratology AU - Heindel, Jerrold J AD - Division of Extramural Research and Training, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Sciences, Research Triangle Park, North Carolina, USA. heindelj@niehs.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 131 EP - 132 VL - 73 IS - 3 SN - 1542-0752, 1542-0752 KW - Index Medicus KW - Animals KW - Humans KW - Gene Expression Regulation, Developmental -- drug effects KW - Female KW - Pregnancy KW - Disease Susceptibility -- etiology KW - Disease Susceptibility -- embryology KW - Environmental Exposure -- adverse effects KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67566105?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+A%2C+Clinical+and+molecular+teratology&rft.atitle=The+fetal+basis+of+adult+disease%3A+Role+of+environmental+exposures--introduction.&rft.au=Heindel%2C+Jerrold+J&rft.aulast=Heindel&rft.aufirst=Jerrold&rft.date=2005-03-01&rft.volume=73&rft.issue=3&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Birth+defects+research.+Part+A%2C+Clinical+and+molecular+teratology&rft.issn=15420752&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-23 N1 - Date created - 2005-03-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective ablation of nociceptive neurons for elimination of hyperalgesia and neurogenic inflammation. AN - 67559095; 15796388 AB - Neuropathic pain is mediated by nociceptive neurons that selectively express the vanilloid receptor 1 (VR1). Resiniferatoxin (RTX) is an excitotoxic VR1 agonist that causes destruction of VR1-positive neurons. To determine whether RTX can be used to ablate VR1-positive neurons selectively and to eliminate hyperalgesia and neurogenic inflammation without affecting tactile sensation and motor function, the authors infused it unilaterally into the trigeminal ganglia in Rhesus monkeys. Either RTX (three animals) or vehicle (one animal) was directly infused (20 microl) into the right trigeminal ganglion in Rhesus monkeys. Animals were tested postoperatively at 1, 4, and 7 weeks thereafter for touch and pain perception in the trigeminal distribution (application of saline and capsaicin to the cornea). The number of eye blinks, eye wipes, and duration of squinting were recorded. Neurogenic inflammation was tested using capsaicin cream. Animals were killed 4 (one monkey) and 12 (three monkeys) weeks postinfusion. Histological and immunohistochemical analyses were performed. Throughout the duration of the study, response to high-intensity pain stimulation (capsaicin) was selectively and significantly reduced (p < 0.001, RTX-treated compared with vehicle-treated eye [mean +/- standard deviation]): blinks, 25.7 +/- 4.4 compared with 106.6 +/- 20.8; eye wipes, 1.4 +/- 0.8 compared with 19.3 +/- 2.5; and squinting, 1.4 +/- 0.6 seconds compared with 11.4 +/- 1.6 seconds. Normal response to sensation was maintained. Animals showed no neurological deficit or sign of toxicity. Neurogenic inflammation was blocked on the RTX-treated side. Immunohistochemical analysis of the RTX-treated ganglia showed selective elimination of VR1-positive neurons. Nociceptive neurons can be selectively ablated by intraganglionic RTX infusion, resulting in the elimination of high-intensity pain perception and neurogenic inflammation while maintaining normal sensation and motor function. Analysis of these findings indicated that intraganglionic RTX infusion may provide a new treatment for pain syndromes such as trigeminal neuralgia as well as others. JF - Journal of neurosurgery AU - Tender, Gabriel C AU - Walbridge, Stuart AU - Olah, Zoltan AU - Karai, Laszlo AU - Iadarola, Michael 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 - 2005/03// PY - 2005 DA - March 2005 SP - 522 EP - 525 VL - 102 IS - 3 SN - 0022-3085, 0022-3085 KW - Diterpenes KW - 0 KW - resiniferatoxin KW - A5O6P1UL4I KW - Capsaicin KW - S07O44R1ZM KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Trigeminal Ganglion -- drug effects KW - Macaca mulatta KW - Immunohistochemistry KW - Capsaicin -- pharmacology KW - Neurogenic Inflammation -- pathology KW - Hyperalgesia -- pathology KW - Diterpenes -- administration & dosage KW - Neurogenic Inflammation -- drug therapy KW - Neurons, Afferent -- drug effects KW - Diterpenes -- therapeutic use KW - Nociceptors -- drug effects KW - Hyperalgesia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67559095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+ablation+of+nociceptive+neurons+for+elimination+of+hyperalgesia+and+neurogenic+inflammation.&rft.au=Tender%2C+Gabriel+C%3BWalbridge%2C+Stuart%3BOlah%2C+Zoltan%3BKarai%2C+Laszlo%3BIadarola%2C+Michael%3BOldfield%2C+Edward+H%3BLonser%2C+Russell+R&rft.aulast=Tender&rft.aufirst=Gabriel&rft.date=2005-03-01&rft.volume=102&rft.issue=3&rft.spage=522&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 - 2005-04-15 N1 - Date created - 2005-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Introduction: new dynamics of HIV risk among drug-using men who have sex with men. AN - 67525389; 15738326 JF - Journal of urban health : bulletin of the New York Academy of Medicine AU - Lambert, Elizabeth AU - Normand, Jacques AU - Stall, Ron AU - Aral, Sevgi AU - Vlahov, David Y1 - 2005/03// PY - 2005 DA - March 2005 SP - i1 EP - i8 VL - 82 IS - 1 Suppl 1 KW - Index Medicus KW - Sexual Behavior KW - Risk-Taking KW - Public Health Practice KW - Humans KW - Urban Population KW - Male KW - HIV Infections -- transmission KW - HIV Infections -- prevention & control KW - Substance-Related Disorders -- complications KW - HIV Infections -- epidemiology KW - Homosexuality, Male -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67525389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Substrate+specificity+of+the+human+protein+phosphatase+2Cdelta%2C+Wip1.&rft.au=Yamaguchi%2C+Hiroshi%3BMinopoli%2C+Giuseppina%3BDemidov%2C+Oleg+N%3BChatterjee%2C+Deb+K%3BAnderson%2C+Carl+W%3BDurell%2C+Stewart+R%3BAppella%2C+Ettore&rft.aulast=Yamaguchi&rft.aufirst=Hiroshi&rft.date=2005-04-12&rft.volume=44&rft.issue=14&rft.spage=5285&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-15 N1 - Date created - 2005-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thr105Ile, a functional polymorphism of histamine N-methyltransferase, is associated with alcoholism in two independent populations. AN - 67514388; 15770103 AB - Histamine is expressed in cortical and limbic areas that are involved in emotion and cognition and modulates these behaviors. H1 receptor antagonists are sedative. Histamine N-methyltransferase (HNMT) catalyzes the Ntau methylation of histamine, the sole pathway for termination of the neurotransmitter action of histamine in mammalian brain. A common and functionally significant polymorphism, a C314T transition in exon 4 of the HNMT gene results in a Thr105Ile substitution of the protein encoded. The Thr105 allele is associated with approximately 2-fold higher enzyme activity, leading to the prediction that it might be associated with diminished histamine levels, resulting in differences in anxiety, cognition, and sedation that play important roles in alcoholism. In two ethnically distinct populations, we tested whether the Thr105Ile polymorphism was associated with alcoholism and with harm avoidance, a dimensional measure of anxious personality. A 5' exonuclease assay (TaqMan) was used to genotype Thr105Ile in psychiatrically interviewed Finnish Caucasian (n = 218) and Plains American Indian (n = 186) alcoholics, along with ethnically matched, psychiatrically interviewed, controls (Finns: n = 313, Plains Indian: n = 140). Ile105 allele frequencies were significantly lower in alcoholics compared with nonalcoholics in both populations (Finns: 0.12 vs. 0.17, chi(2) = 6, p = 0.015; Plains Indians: 0.03 vs. 0.08, chi(2) = 5, p = 0.023). Genotype distributions also differed significantly. In Finns, Ile105 showed borderline significance for an association with lower harm avoidance (p = 0.070) after correcting for alcoholism diagnosis. Decreased levels of brain histamine consequent to the Thr105 allele may result in higher levels of anxiety and, as a consequence, vulnerability to alcoholism. JF - Alcoholism, clinical and experimental research AU - Oroszi, Gabor AU - Enoch, Mary-Anne AU - Chun, Jeffrey AU - Virkkunen, Matti AU - Goldman, David AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA. goroszi@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 303 EP - 309 VL - 29 IS - 3 SN - 0145-6008, 0145-6008 KW - Histamine N-Methyltransferase KW - EC 2.1.1.8 KW - Phosphodiesterase I KW - EC 3.1.4.1 KW - Index Medicus KW - Anxiety -- psychology KW - Gene Frequency KW - Personality Tests KW - Polymorphism, Genetic -- genetics KW - Humans KW - Phosphodiesterase I -- genetics KW - Genotype KW - Alleles KW - Indians, North American KW - Psychiatric Status Rating Scales KW - Anxiety -- genetics KW - European Continental Ancestry Group KW - Adult KW - United States -- epidemiology KW - Finland -- epidemiology KW - Female KW - Male KW - Histamine N-Methyltransferase -- genetics KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67514388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thr105Ile%2C+a+functional+polymorphism+of+histamine+N-methyltransferase%2C+is+associated+with+alcoholism+in+two+independent+populations.&rft.au=Oroszi%2C+Gabor%3BEnoch%2C+Mary-Anne%3BChun%2C+Jeffrey%3BVirkkunen%2C+Matti%3BGoldman%2C+David&rft.aulast=Oroszi&rft.aufirst=Gabor&rft.date=2005-03-01&rft.volume=29&rft.issue=3&rft.spage=303&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 - 2005-06-27 N1 - Date created - 2005-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The conventional nonsteroidal anti-inflammatory drug sulindac sulfide arrests ovarian cancer cell growth via the expression of NAG-1/MIC-1/GDF-15. AN - 67513850; 15767558 AB - Although the chemopreventive and antitumorigenic activities of nonsteroidal anti-inflammatory drug (NSAID) against colorectal cancer are well established, the molecular mechanisms responsible for these properties in ovarian cancer have not been elucidated. Therefore, there is an urgent need to develop mechanism-based approaches for the management of ovarian cancer. To this end, the effect of several NSAIDs on ovarian cancer cells was investigated as assessed by the induction of NAG-1/MIC-1/GDF-15, a proapoptotic gene belonging to the transforming growth factor-beta superfamily. Sulindac sulfide was the most significant NSAID activated gene 1 (NAG-1) inducer and its expression was inversely associated with cell viability as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. This growth suppression by sulindac sulfide was recovered by transfection of NAG-1 small interfering RNA. These results indicate that NAG-1 is one of the genes responsible for growth suppression by sulindac sulfide. Furthermore, we observed down-regulation of p21 WAF1/CIP1 by introduction of NAG-1 small interfering RNA into sulindac sulfide-treated cells. In addition, to elucidate other potential molecular mechanisms involved in sulindac sulfide treatment of ovarian cancer cells, we did a membrane-based microarray experiment. We found that cyclin D1, MMP-1, PI3KR1, and uPA were down-regulated by sulindac sulfide. In conclusion, a novel molecular mechanism is proposed to explain the experimental results and provide a rationale for the chemopreventive activity of NSAIDs in ovarian cancer. JF - Molecular cancer therapeutics AU - Kim, Jong-Sik AU - Baek, Seung Joon AU - Sali, Tina AU - Eling, Thomas E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, MD: E4-09, P.O. Box 12233, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 487 EP - 493 VL - 4 IS - 3 SN - 1535-7163, 1535-7163 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - CDKN1A protein, human KW - Cell Cycle Proteins KW - Coloring Agents KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cytokines KW - GDF15 protein, human KW - Growth Differentiation Factor 15 KW - RNA, Small Interfering KW - Tetrazolium Salts KW - Thiazoles KW - Cyclin D1 KW - 136601-57-5 KW - Sulindac KW - 184SNS8VUH KW - sulindac sulfide KW - 6UVA8S2DEY KW - Luciferases KW - EC 1.13.12.- KW - thiazolyl blue KW - EUY85H477I KW - Index Medicus KW - Coloring Agents -- pharmacology KW - Apoptosis KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Luciferases -- metabolism KW - Cell Line, Tumor KW - Cytokines -- metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - Tetrazolium Salts -- pharmacology KW - RNA, Small Interfering -- metabolism KW - Cell Cycle Proteins -- metabolism KW - Cell Survival KW - Thiazoles -- pharmacology KW - Promoter Regions, Genetic KW - Blotting, Western KW - Cyclin D1 -- metabolism KW - Down-Regulation KW - Up-Regulation KW - Time Factors KW - Female KW - Ovarian Neoplasms -- metabolism KW - Sulindac -- pharmacology KW - Sulindac -- analogs & derivatives KW - Ovarian Neoplasms -- drug therapy KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67513850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+conventional+nonsteroidal+anti-inflammatory+drug+sulindac+sulfide+arrests+ovarian+cancer+cell+growth+via+the+expression+of+NAG-1%2FMIC-1%2FGDF-15.&rft.au=Kim%2C+Jong-Sik%3BBaek%2C+Seung+Joon%3BSali%2C+Tina%3BEling%2C+Thomas+E&rft.aulast=Kim&rft.aufirst=Jong-Sik&rft.date=2005-03-01&rft.volume=4&rft.issue=3&rft.spage=487&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 - 2005-06-28 N1 - Date created - 2005-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Developmental phases of inflammation-induced massive lymphoid hyperplasia and extensive changes in epithelium in an experimental model of allergy: implications for a direct link between inflammation and carcinogenesis. AN - 67513653; 15767829 AB - Direct evidence that inflammation is linked to carcinogenesis has yet to be established. Very few data are available on the developmental phases of inflammation-induced immune dysfunction that may lead to tumorigenesis. In a series of studies conducted in the 1980s and 1990s, an experimental model of acute and chronic inflammation was established in guinea pig conjunctiva by topical application of fluoresceinyl ovalbumin (FLOA) for up to 30 months. In this updated report, some of the findings are reanalyzed and expanded to identify that at lease 3 developmental phases were involved during the entire course of inflammatory responses including (1) an acute response (phase A) involving IgE-mast cell sensitization and degranulation; (2) an intermediate phase (phase B), a desensitization phenomenon and loss of mast cell function and neovascularization; (3) a chronic response (phase C) and induction of massive lymphoid hyperplasia, follicular formation with germinal centers, increased swollen goblet cells, extensive epithelial thickening and thinning, and angiogenesis. The results suggest evidence of a direct association between inflammation and the development of tumor-like lesions in lymphoid tissues and extensive changes in adjacent epithelia. Confirmation that inflammation induces irreversible changes in lymphoid and epithelial tissues leading to lymphoid tumorigenesis and/or carcinogenesis requires further studies. Understanding the developmental phases of immune dysfunction may provide unique opportunities for diagnosis and treatment of inflammatory diseases, autoimmune disorders, and cancers including lymphomas associated with Sjogren syndrome, squamous cell carcinoma of the conjunctiva, and other lymphomas or epithelial cancers. It is suggested that inflammatory mediators are ideal targets (biomarkers) for diagnosis, chemoprevention, and therapy for several cancers. JF - American journal of therapeutics AU - Khatami, Mahin AD - University of Pennsylvania School of Medicine, Philadelphia, PA, USA. Khatamim@mail.nih.gov PY - 2005 SP - 117 EP - 126 VL - 12 IS - 2 SN - 1075-2765, 1075-2765 KW - Inflammation Mediators KW - 0 KW - Index Medicus KW - Acute Disease KW - Animals KW - Mast Cells -- immunology KW - Hypersensitivity, Immediate -- immunology KW - Cell Degranulation KW - Hyperplasia -- immunology KW - Guinea Pigs KW - Antibody Formation KW - Disease Models, Animal KW - Haplorhini KW - Inflammation Mediators -- metabolism KW - Neovascularization, Pathologic -- immunology KW - Animals, Newborn KW - Neovascularization, Pathologic -- etiology KW - Hyperplasia -- etiology KW - Dogs KW - Chronic Disease KW - Epithelium -- pathology KW - Lymphoid Tissue -- pathology KW - Conjunctivitis, Allergic -- pathology KW - Lymphoid Tissue -- immunology KW - Conjunctivitis, Allergic -- immunology KW - Conjunctivitis, Allergic -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67513653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Developmental+phases+of+inflammation-induced+massive+lymphoid+hyperplasia+and+extensive+changes+in+epithelium+in+an+experimental+model+of+allergy%3A+implications+for+a+direct+link+between+inflammation+and+carcinogenesis.&rft.au=Khatami%2C+Mahin&rft.aulast=Khatami&rft.aufirst=Mahin&rft.date=2005-03-01&rft.volume=12&rft.issue=2&rft.spage=117&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 - 2005-07-08 N1 - Date created - 2005-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The validation of a pesticide exposure algorithm using biological monitoring results. AN - 67508006; 15764542 AB - A pesticide exposure algorithm was developed to calculate pesticide exposure intensity scores based on responses to questions about pesticide handling procedures and application methods in a self-administered questionnaire. The validity of the algorithm was evaluated through comparison of the algorithm scores with biological monitoring data from a study of 126 pesticide applicators who applied the herbicides MCPA or 2,4-D. The variability in the algorithm scores calculated for these applicators was due primarily to differences in their use of personal protective equipment (PPE). Rubber gloves were worn by 75% of applicators when mixing and 22% when applying pesticides, rubber boots were worn by 33% when mixing and 23% when applying, and goggles were worn by 33% and 17% of applicators when mixing and when applying, respectively. Only 2% of applicators wore all three types of PPE when both mixing and applying, and 15% wore none of these three types of PPE when either mixing or applying. Substantial variability was also observed in the concentrations of pesticides detected in the post application urine samples. The concentration of MCPA detected in urine samples collected on the second day after the application ranged from less than < 1.0 to 610 microg/L among 84 of the applicators who applied MCPA. The concentrations of 2,4-D detected in the urine samples ranged from less than < 1.0 to 514 microg/L among 41 of the applicators who applied 2,4-D. When categorized into three groups based on the algorithm scores, the geometric mean in the highest exposure group was 20 microg/L compared with 5 microg/L in the lowest exposure group for the MCPA applicators, and 29 microg/L in highest exposure group compared with 2 microg/L in the low exposure group for the 2,4-D applicators. A regression analysis detected statistically significant trends in the geometric mean of the urine concentrations across the exposure categories for both the 2,4-D and the MCPA applicators. The algorithm scores, based primarily on the use of PPE, appear to provide a reasonably valid measure of exposure intensity for these applicators, however, further studies are needed to generalize these results to other types of pesticides and application methods. JF - Journal of occupational and environmental hygiene AU - Coble, Joseph AU - Arbuckle, Tye AU - Lee, Wonjin AU - Alavanja, Michael AU - Dosemeci, Mustafa AD - Department of Cancer Epidemiology and Genetics, National Cancer Institute, Occupational and Environmental Epidemiology Branch, NIH, DHHS, Rockville, Maryland 20892-7240, USA. jcoble@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 194 EP - 201 VL - 2 IS - 3 SN - 1545-9624, 1545-9624 KW - Herbicides KW - 0 KW - 2,4-Dichlorophenoxyacetic Acid KW - 2577AQ9262 KW - 2-Methyl-4-chlorophenoxyacetic Acid KW - D888C394VO KW - Index Medicus KW - Sensitivity and Specificity KW - Gloves, Protective KW - Data Collection -- methods KW - Protective Clothing KW - Humans KW - Environmental Monitoring -- standards KW - Predictive Value of Tests KW - Environmental Monitoring -- methods KW - Occupational Exposure KW - Herbicides -- adverse effects KW - 2,4-Dichlorophenoxyacetic Acid -- analysis KW - 2,4-Dichlorophenoxyacetic Acid -- adverse effects KW - Herbicides -- analysis KW - 2-Methyl-4-chlorophenoxyacetic Acid -- analysis KW - Surveys and Questionnaires KW - Algorithms KW - 2-Methyl-4-chlorophenoxyacetic Acid -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67508006?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+hygiene&rft.atitle=The+validation+of+a+pesticide+exposure+algorithm+using+biological+monitoring+results.&rft.au=Coble%2C+Joseph%3BArbuckle%2C+Tye%3BLee%2C+Wonjin%3BAlavanja%2C+Michael%3BDosemeci%2C+Mustafa&rft.aulast=Coble&rft.aufirst=Joseph&rft.date=2005-03-01&rft.volume=2&rft.issue=3&rft.spage=194&rft.isbn=&rft.btitle=&rft.title=Journal+of+occupational+and+environmental+hygiene&rft.issn=15459624&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-24 N1 - Date created - 2005-03-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interfacial inhibition of macromolecular interactions: nature's paradigm for drug discovery. AN - 67490217; 15749159 AB - One of nature's strategies for interfering with molecular interactions is to trap macromolecules in transition states with their partners in dead-end complexes that are unable to complete their biological function. This type of inhibition, which we refer to as "interfacial inhibition", is illustrated by two natural inhibitors, brefeldin A (BFA) and camptothecin (CPT), whose modes of action have been elucidated fully in structural studies. Interfacial inhibition occurs at the protein-protein interface in the case of BFA and at the protein-DNA interface in the case of CPT. In both systems, the drugs take advantage of transient structural and energetic conditions created by the macromolecular complex, which give rise to "hot-spots" for drug binding. In addition to these examples, several natural compounds such as forskolin, tubulin inhibitors and immunophilins target protein interfaces. We propose that interfacial inhibition is a paradigm for the discovery of drugs that interfere with macromolecular complexes. JF - Trends in pharmacological sciences AU - Pommier, Yves AU - Cherfils, Jacqueline AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Pommier@nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 138 EP - 145 VL - 26 IS - 3 SN - 0165-6147, 0165-6147 KW - Macromolecular Substances KW - 0 KW - Pharmaceutical Preparations KW - Index Medicus KW - Protein Binding -- physiology KW - Animals KW - Protein Binding -- drug effects KW - Humans KW - Drug Interactions -- physiology KW - Pharmaceutical Preparations -- metabolism KW - Pharmaceutical Preparations -- chemistry KW - Macromolecular Substances -- antagonists & inhibitors KW - Macromolecular Substances -- metabolism KW - Macromolecular Substances -- chemistry KW - Drug Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67490217?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interfacial+inhibition+of+macromolecular+interactions%3A+nature%27s+paradigm+for+drug+discovery.&rft.au=Pommier%2C+Yves%3BCherfils%2C+Jacqueline&rft.aulast=Pommier&rft.aufirst=Yves&rft.date=2005-03-01&rft.volume=26&rft.issue=3&rft.spage=138&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 - 2005-04-26 N1 - Date created - 2005-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - No phenotype associated with established lipopolysaccharide model for cerebral palsy. AN - 67487182; 15746664 AB - Cerebral palsy (CP) is associated with childhood spasticity, seizures, and paralysis. Oligodendrocyte damage resulting in periventicular leukomalacia (PVL) in the developing brain has been implicated. Animal models of CP have used prenatal hypoxia and infection with histopathology of PVL as the end point. To evaluate whether this histologic end point is associated with a CP phenotype, we reproduced a lipopolysaccharide (LPS) model for PVL, 1 and evaluated developmental, behavioral, and motor outcomes. On gestational day 15, Fischer 344 rats were intracervically injected with .1 mg/kg LPS (n = 5) or saline (n = 4). After delivery, evaluation for developmental milestones was performed on days 1 to 21 (LPS = 45; control = 30 pups). Males were also tested at 2.5 months using open-field, rotarod, and anxiety tests. On day 21, 2 pups/litter were perfused for immunohistochemistry, and stained with 2 oligodendrocyte antibodies: 2', d'-cyclic nucleotide phosphodiesterase (CNP), and myelin proteolipid protein (PLP) with relative densities of staining assessed using NIH Image software. Statistical analysis included Mann-Whitney U and analysis of variance (ANOVA). LPS pups demonstrated decreased CNP (P = .04) and PLP (P = .06) staining, replicating the model. There was no difference seen in neonatal weight, righting, negative geotaxis, cliff aversion, rooting, forelimb grasp, audio startle, air righting, eye opening, and activity. Surprisingly, LPS-exposed neonatal rats mastered forelimb placement (P < .01) and surface righting (P = .02) earlier than control rats. There were no differences between adult groups in open field distance traveled (P = .8), open-field locomotion time (P = .6), rotarod (P = .6), or anxiety (P = .7). Histologic evidence of white matter damage can be replicated using an LPS model for intrauterine inflammation. Significant phenotypic differences consistent with the motor and cognitive damage sequelae of such lesions (ie, CP) were not demonstrated. When evaluating animal models, it is important to assess not only biochemical markers for human disease, but also clinically relevant phenotypes. JF - American journal of obstetrics and gynecology AU - Poggi, Sarah H AU - Park, Jane AU - Toso, Laura AU - Abebe, Daniel AU - Roberson, Robin AU - Woodard, Jade E AU - Spong, Catherine Y AD - Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. sarah.poggi@inova.com Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 727 EP - 733 VL - 192 IS - 3 SN - 0002-9378, 0002-9378 KW - Lipopolysaccharides KW - 0 KW - Myelin Proteolipid Protein KW - 2',3'-Cyclic-Nucleotide Phosphodiesterases KW - EC 3.1.4.- KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Myelin Proteolipid Protein -- analysis KW - Animals KW - Rats, Inbred F344 KW - 2',3'-Cyclic-Nucleotide Phosphodiesterases -- analysis KW - Humans KW - Infant, Newborn KW - Disease Models, Animal KW - Immunohistochemistry KW - Male KW - Leukomalacia, Periventricular -- physiopathology KW - Cognition -- physiology KW - Lipopolysaccharides -- administration & dosage KW - Cerebral Palsy -- physiopathology KW - Motor Activity -- physiology KW - Leukomalacia, Periventricular -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67487182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+obstetrics+and+gynecology&rft.atitle=No+phenotype+associated+with+established+lipopolysaccharide+model+for+cerebral+palsy.&rft.au=Poggi%2C+Sarah+H%3BPark%2C+Jane%3BToso%2C+Laura%3BAbebe%2C+Daniel%3BRoberson%2C+Robin%3BWoodard%2C+Jade+E%3BSpong%2C+Catherine+Y&rft.aulast=Poggi&rft.aufirst=Sarah&rft.date=2005-03-01&rft.volume=192&rft.issue=3&rft.spage=727&rft.isbn=&rft.btitle=&rft.title=American+journal+of+obstetrics+and+gynecology&rft.issn=00029378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-01 N1 - Date created - 2005-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The nitric oxide prodrug, V-PYRRO/NO, protects against cadmium toxicity and apoptosis at the cellular level. AN - 67483301; 15740985 AB - The liver is an important target tissue of cadmium. The compound O2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2 diolate (V-PYRRO/NO) is a liver-selective nitric oxide (NO) prodrug that is metabolized by hepatic P450 enzymes to release NO in hepatocytes. In vivo, V-PYRRO/NO can protect against the toxicity of various hepatotoxicants, including cadmium. Since NO is an effective vasodilator, whether this protective effect against cadmium toxicity is at the level of the hepatic vascular system or actually within the liver cells has not been defined. Thus, we studied the effects of V-PYRRO/NO pretreatment on cadmium-induced toxicity and apoptosis in cultured rat liver epithelial (TRL 1215) cells. Cells were pretreated with V-PYRRO/NO at 500 or 1000 microM for up to 24 h, then exposed to cadmium (as CdCl2) for additional 24 h and cytotoxicity was measured. Cadmium was significantly less cytotoxic in V-PYRRO/NO (1000 microM) pretreated cells (LC50=6.1+/-0.6 microM) compared to control cells (LC50=3.5+/-0.4 microM). TRL 1215 cells acted upon the prodrug to release NO, producing nitrite levels in the extracellular media after 24 h of exposure to 500 or 1000 microM V-PYRRO/NO measured at 87.0+/-4.2 and 324+/-14.8 microM, respectively, compared to basal levels of 7.70+/-0.46 microM. V-PYRRO/NO alone produced small increases in metallothionein (MT), a metal-binding protein associated with cadmium tolerance. However, V-PYRRO/NO pretreatment greatly enhanced cadmium induction of MT. V-PYRRO/NO pretreatment also markedly reduced apoptotic cell death induced by cadmium (5 microM), apparently by blocking cadmium-induced activation of the c-Jun N-terminal kinase (JNK) pathway. Thus, the prodrug, V-PYRRO/NO, protects against the adverse effects of cadmium directly within rat liver cells apparently through generation of NO and, at least in part, by facilitation of cadmium-induced MT synthesis. JF - Nitric oxide : biology and chemistry AU - Qu, Wei AU - Liu, Jie AU - Fuquay, Richard AU - Shimoda, Ryuya AU - Sakurai, Teruaki AU - Saavedra, Joseph E AU - Keefer, Larry K AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 114 EP - 120 VL - 12 IS - 2 SN - 1089-8603, 1089-8603 KW - Nitrites KW - 0 KW - O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate KW - Prodrugs KW - Pyrrolidines KW - Nitric Oxide KW - 31C4KY9ESH KW - Metallothionein KW - 9038-94-2 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Cadmium Chloride KW - J6K4F9V3BA KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Nitrites -- metabolism KW - Dose-Response Relationship, Drug KW - Prodrugs -- pharmacology KW - Metallothionein -- drug effects KW - Enzyme-Linked Immunosorbent Assay KW - Nitric Oxide -- biosynthesis KW - Metallothionein -- metabolism KW - JNK Mitogen-Activated Protein Kinases -- drug effects KW - Cell Line KW - JNK Mitogen-Activated Protein Kinases -- metabolism KW - Apoptosis -- physiology KW - Cadmium Chloride -- toxicity KW - Apoptosis -- drug effects KW - Pyrrolidines -- pharmacology KW - Cadmium Chloride -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67483301?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nitric+oxide+%3A+biology+and+chemistry&rft.atitle=The+nitric+oxide+prodrug%2C+V-PYRRO%2FNO%2C+protects+against+cadmium+toxicity+and+apoptosis+at+the+cellular+level.&rft.au=Qu%2C+Wei%3BLiu%2C+Jie%3BFuquay%2C+Richard%3BShimoda%2C+Ryuya%3BSakurai%2C+Teruaki%3BSaavedra%2C+Joseph+E%3BKeefer%2C+Larry+K%3BWaalkes%2C+Michael+P&rft.aulast=Qu&rft.aufirst=Wei&rft.date=2005-03-01&rft.volume=12&rft.issue=2&rft.spage=114&rft.isbn=&rft.btitle=&rft.title=Nitric+oxide+%3A+biology+and+chemistry&rft.issn=10898603&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-26 N1 - Date created - 2005-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 3-hydroxymorphinan is neurotrophic to dopaminergic neurons and is also neuroprotective against LPS-induced neurotoxicity. AN - 67482729; 15596482 AB - The purpose of this study was to develop a novel therapy for Parkinson's disease (PD). We recently reported that dextromethorphan (DM), an active ingredient in a variety of widely used anticough remedies, protected dopaminergic neurons in rat primary mesencephalic neuron-glia cultures against lipopolysaccharide (LPS)-mediated degeneration and provided potent protection for dopaminergic neurons in a MPTP mouse model. The underlying mechanism for the protective effect of DM was attributed to its anti-inflammatory activity through inhibition of microglia activation. In an effort to develop more potent compounds for the treatment of PD, we have screened a series of analogs of DM, and 3-hydroxymorphinan (3-HM) emerged as a promising candidate for this purpose. Our study using primary mesencephalic neuron-glia cultures showed that 3-HM provided more potent neuroprotection against LPS-induced dopaminergic neurotoxicity than its parent compound. The higher potency of 3-HM was attributed to its neurotrophic effect in addition to the anti-inflammatory effect shared by both DM and 3-HM. First, we showed that 3-HM exerted potent neuroprotective and neurotrophic effects on dopaminergic neurons in rat primary mesencephalic neuron-glia cultures treated with LPS. The neurotrophic effect of 3-HM was glia-dependent since 3-HM failed to show any protective effect in the neuron-enriched cultures. We subsequently demonstrated that it was the astroglia, not the microglia, that contributed to the neurotrophic effect of 3-HM. This conclusion was based on the reconstitution studies, in which we added different percentages of microglia (10-20%) or astroglia (40-50%) back to the neuron-enriched cultures and found that 3-HM was neurotrophic after the addition of astroglia, but not microglia. Furthermore, 3-HM-treated astroglia-derived conditioned media exerted a significant neurotrophic effect on dopaminergic neurons. It appeared likely that 3-HM caused the release of neurotrophic factor(s) from astroglia, which in turn was responsible for the neurotrophic effect. Second, the anti-inflammatory mechanism was also important for the neuroprotective activity of 3-HM because the more microglia were added back to the neuron-enriched cultures, the more significant neuroprotective effect was observed. The anti-inflammatory mechanism of 3-HM was attributed to its inhibition of LPS-induced production of an array of pro-inflammatory and neurotoxic factors, including nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2) and reactive oxygen species (ROS). In conclusion, this study showed that 3-HM exerted potent neuroprotection by acting on two different targets: a neurotrophic effect mediated by astroglia and an anti-inflammatory effect mediated by the inhibition of microglial activation. 3-HM thus possesses these two important features necessary for an effective neuroprotective agent. In view of the well-documented very low toxicity of DM and its analogs, this report may provide an important new direction for the development of therapeutic interventions for inflammation-related diseases such as PD. JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology AU - Zhang, Wei AU - Qin, Liya AU - Wang, Tongguang AU - Wei, Sung-Jen AU - Gao, Hui-ming AU - Liu, Jie AU - Wilson, Belinda AU - Liu, Bin AU - Zhang, Wanqin AU - Kim, Hyoung-Chun AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, P.O. Box 12233, NC, USA. zhang11@niehs.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 395 EP - 397 VL - 19 IS - 3 KW - Anti-Inflammatory Agents KW - 0 KW - Culture Media, Conditioned KW - Lipopolysaccharides KW - Nerve Growth Factors KW - Neuroprotective Agents KW - Reactive Oxygen Species KW - Tumor Necrosis Factor-alpha KW - Nitric Oxide KW - 31C4KY9ESH KW - Dextromethorphan KW - 7355X3ROTS KW - norlevorphanol KW - IL94262N7K KW - Dinoprostone KW - K7Q1JQR04M KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Dinoprostone -- biosynthesis KW - Astrocytes -- drug effects KW - Astrocytes -- physiology KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Neuroglia -- drug effects KW - Nitric Oxide -- biosynthesis KW - Mesencephalon -- cytology KW - Neuroglia -- physiology KW - Parkinson Disease -- drug therapy KW - Rats KW - Microglia -- physiology KW - Microglia -- drug effects KW - Anti-Inflammatory Agents -- pharmacology KW - Dextromethorphan -- analogs & derivatives KW - Nerve Growth Factors -- pharmacology KW - Lipopolysaccharides -- antagonists & inhibitors KW - Neurons -- drug effects KW - Dextromethorphan -- pharmacology KW - Neurons -- physiology KW - Dopamine -- physiology KW - Lipopolysaccharides -- toxicity KW - Neuroprotective Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67482729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=3-hydroxymorphinan+is+neurotrophic+to+dopaminergic+neurons+and+is+also+neuroprotective+against+LPS-induced+neurotoxicity.&rft.au=Zhang%2C+Wei%3BQin%2C+Liya%3BWang%2C+Tongguang%3BWei%2C+Sung-Jen%3BGao%2C+Hui-ming%3BLiu%2C+Jie%3BWilson%2C+Belinda%3BLiu%2C+Bin%3BZhang%2C+Wanqin%3BKim%2C+Hyoung-Chun%3BHong%2C+Jau-Shyong&rft.aulast=Zhang&rft.aufirst=Wei&rft.date=2005-03-01&rft.volume=19&rft.issue=3&rft.spage=395&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 - 2005-10-25 N1 - Date created - 2005-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vitamin A supplementation for extremely low birth weight infants: outcome at 18 to 22 months. AN - 67482339; 15713907 AB - A National Institute of Child Health and Human Development Neonatal Research Network randomized trial showed that vitamin A supplementation reduced bronchopulmonary dysplasia (O2 at 36 weeks' postmenstrual age) or death in extremely low birth weight (ELBW) neonates (relative risk [RR]: 0.89). As with postnatal steroids or other interventions, it is important to ensure that there are no longer-term adverse effects that outweigh neonatal benefits. To determine if vitamin A supplementation in ELBW infants during the first month after birth affects survival without neurodevelopmental impairment at a corrected age of 18 to 22 months. Infants enrolled in the National Institute of Child Health and Human Development vitamin A trial were evaluated at 18 to 22 months by carefully standardized assessments: Bayley Mental Index (MDI) and Psychomotor Index (PDI), visual and hearing screens, and physical examination for cerebral palsy (CP). The medical history was also obtained. Neurodevelopmental impairment (NDI) was predefined as > or =1 of MDI <70, PDI <70, CP, blind in both eyes, or hearing aids in both ears. Of 807 enrolled infants, 133 died before and 16 died after discharge. Five hundred seventy-nine (88%) of the 658 remaining infants were followed up. The primary outcome of NDI or death could be determined for 687 of 807 randomized infants (85%). Baseline characteristics and predischarge and postdischarge mortality were comparable in both study groups. NDI or death by 18 to 22 months occurred in 190 of 345 (55%) infants in the vitamin A group and in 204 of 342 (60%) of the control group (RR: 0.94; 95% confidence interval: 0.80-1.07). RRs for low MDI, low PDI, and CP were also <1.0. We found no evidence that neonatal vitamin A supplementation reduces hospitalizations or pulmonary problems after discharge. Vitamin A supplementation for ELBW infants reduces bronchopulmonary dysplasia without increasing mortality or neurodevelopmental impairment at 18 to 22 months. However, this study was not powered to evaluate small magnitudes of change in long-term outcomes. JF - Pediatrics AU - Ambalavanan, Namasivayam AU - Tyson, Jon E AU - Kennedy, Kathleen A AU - Hansen, Nellie I AU - Vohr, Betty R AU - Wright, Linda L AU - Carlo, Waldemar A AU - National Institute of Child Health and Human Development Neonatal Research Network AD - Department of Pediatrics, University of Alabama, Birmingham, Alabama 35249, USA. ambal@uab.edu ; National Institute of Child Health and Human Development Neonatal Research Network Y1 - 2005/03// PY - 2005 DA - March 2005 SP - e249 EP - e254 VL - 115 IS - 3 KW - Vitamin A KW - 11103-57-4 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Infant, Newborn KW - Infant Mortality KW - Follow-Up Studies KW - Neuropsychological Tests KW - Cerebral Palsy -- chemically induced KW - Male KW - Female KW - Vitamin A -- therapeutic use KW - Infant, Very Low Birth Weight KW - Developmental Disabilities -- chemically induced KW - Vitamin A -- adverse effects KW - Bronchopulmonary Dysplasia -- prevention & control KW - Child Development -- drug effects KW - Developmental Disabilities -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67482339?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vitamin+A+supplementation+for+extremely+low+birth+weight+infants%3A+outcome+at+18+to+22+months.&rft.au=Ambalavanan%2C+Namasivayam%3BTyson%2C+Jon+E%3BKennedy%2C+Kathleen+A%3BHansen%2C+Nellie+I%3BVohr%2C+Betty+R%3BWright%2C+Linda+L%3BCarlo%2C+Waldemar+A%3BNational+Institute+of+Child+Health+and+Human+Development+Neonatal+Research+Network&rft.aulast=Ambalavanan&rft.aufirst=Namasivayam&rft.date=2005-03-01&rft.volume=115&rft.issue=3&rft.spage=e249&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 - 2005-06-17 N1 - Date created - 2005-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational exposure to carbofuran and the incidence of cancer in the Agricultural Health Study. AN - 67477836; 15743716 AB - Carbofuran is a carbamate insecticide registered for use on a variety of food crops including corn, alfalfa, rice, and tobacco. An estimated 5 million pounds of carbofuran is used annually in the United States, and 45% of urban African-American women have detectable levels of carbofuran in their plasma. Nitrosated carbofuran has demonstrated mutagenic properties. We examined exposure to carbofuran and several tumor sites among 49,877 licensed pesticide applicators from Iowa and North Carolina enrolled in the Agricultural Health Study. We obtained information regarding years of use, frequency of use in an average year, and when use began for 22 pesticides using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals (CIs) adjusting for potential confounders. Lung cancer risk was 3-fold higher for those with > 109 days of lifetime exposure to carbofuran (RR = 3.05; 95% CI, 0.94-9.87) compared with those with < 9 lifetime exposure days, with a significant dose-response trend for both days of use per year and total years of use. However, carbofuran use was not associated with lung cancer risk when nonexposed persons were used as the referent. In addition, carbofuran exposure was not associated with any other cancer site examined. Although carbamate pesticides are suspected human carcinogens, these results should be interpreted cautiously because there was no a priori hypothesis specifically linking carbofuran to lung cancer. JF - Environmental health perspectives AU - Bonner, Matthew R AU - Lee, Won Jin AU - Sandler, Dale P AU - Hoppin, Jane A AU - Dosemeci, Mustafa AU - Alavanja, Michael C R AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA. bonnerm@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 285 EP - 289 VL - 113 IS - 3 SN - 0091-6765, 0091-6765 KW - Insecticides KW - 0 KW - Carbofuran KW - SKF77S6Y67 KW - Index Medicus KW - Agriculture KW - Epidemiologic Studies KW - Humans KW - Adult KW - Incidence KW - Aged KW - Middle Aged KW - North Carolina -- epidemiology KW - Male KW - Iowa -- epidemiology KW - Female KW - Occupational Exposure KW - Insecticides -- poisoning KW - Neoplasms -- epidemiology KW - Carbofuran -- poisoning KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67477836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Occupational+exposure+to+carbofuran+and+the+incidence+of+cancer+in+the+Agricultural+Health+Study.&rft.au=Bonner%2C+Matthew+R%3BLee%2C+Won+Jin%3BSandler%2C+Dale+P%3BHoppin%2C+Jane+A%3BDosemeci%2C+Mustafa%3BAlavanja%2C+Michael+C+R&rft.aulast=Bonner&rft.aufirst=Matthew&rft.date=2005-03-01&rft.volume=113&rft.issue=3&rft.spage=285&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 - 2005-07-18 N1 - Date created - 2005-03-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mutat Res. 1983 Mar;116(3-4):185-216 [6339892] J Environ Pathol Toxicol. 1980 Nov;4(5-6):53-63 [7217860] IARC Sci Publ. 1987;(82):1-406 [3329634] J Occup Med. 1990 Oct;32(10):996-1002 [2262830] Cancer Causes Control. 1993 Sep;4(5):449-54 [8218877] Cancer Causes Control. 1994 Jul;5(4):310-8 [8080942] J Toxicol Environ Health. 1994 Dec;43(4):383-418 [7990167] Environ Health Perspect. 1996 Apr;104(4):362-9 [8732939] Am J Ind Med. 1996 Nov;30(5):601-9 [8909609] Mutagenesis. 1998 Mar;13(2):157-66 [9568589] Int J Epidemiol. 1999 Jun;28(3):365-74 [10405835] Environ Res. 1986 Dec;41(2):633-45 [3490967] Toxicology. 2000 Feb 7;143(1):1-118 [10675783] Mutat Res. 2000 Feb 16;465(1-2):123-9 [10708977] J Occup Environ Med. 2001 Jul;43(7):641-9 [11464396] Cancer Epidemiol Biomarkers Prev. 2001 Nov;10(11):1155-63 [11700263] Toxicology. 2001 Dec 14;169(2):153-61 [11718956] Epidemiology. 2002 Jan;13(1):94-9 [11805592] Ann Occup Hyg. 2002 Mar;46(2):245-60 [12074034] Environ Health Perspect. 2003 May;111(5):749-56 [12727605] J Allergy Clin Immunol. 2003 Jul;112(1):219-20 [12847509] Ann Agric Environ Med. 2003;10(2):229-32 [14677917] Arch Environ Health. 2003 May;58(5):316-7; author reply 317 [14738278] J Occup Med. 1970 Jan;12(1):16-9 [5410616] Toxicol Appl Pharmacol. 1975 Jun;32(3):587-602 [50651] Int J Cancer. 1976 Jun 15;17(6):742-7 [988851] Neoplasma. 1977;24(1):119-22 [576495] Erratum In: Environ Health Perspect. 2005 May;113(5):A297 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Invasive human magnetic resonance imaging: feasibility during revascularization in a combined XMR suite. AN - 67477527; 15736247 AB - We tested the feasibility and safety of invasive magnetic resonance imaging (MRI) during peripheral angioplasty. Real-time MRI can image soft tissue and may potentially guide therapeutic procedures without ionizing radiation or nephrotoxic contrast. MRI-guided diagnostic catheterization has been described recently, but safe and conspicuous catheter devices are not widely available. An active guidewire, which serves as an MRI receiver antenna, might be useful to guide catheterization or even to image atheroma. We describe a combined interventional suite offering both X-ray fluoroscopy and real-time MRI. We used a 0.030'' active guidewire receiver coil for invasive MRI after X-ray lesion traversal in patients undergoing percutaneous iliofemoral artery revascularization. Intravascular MRI was compared with noninvasive MRI, X-ray angiography, and intravascular ultrasound (IVUS). Seven eligible patients consented to participate, but three were excluded because of lengthy revascularization procedures. Four remaining patients safely underwent combined X-ray fluoroscopy and real-time magnetic resonance imaging (XMR) transport, continuous monitoring, and all imaging modalities. There was no device dislodgment, contamination or evidence of heating. The intravascular MRI coil was well visualized except at the tip, but did not provide superior mural imaging compared with IVUS. Therefore, because an adequate safety and workflow experience was obtained, enrollment was terminated after only four subjects. Invasive MRI is feasible and apparently safe during peripheral angioplasty. Patients can safely be transported and monitored in an XMR interventional suite. An active quarter-wavelength guidewire coil does not provide superior imaging compared with IVUS, but provides satisfactory guidewire visualization. These tools may prove useful for advanced therapeutic procedures in the future. JF - Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions AU - Dick, Alexander J AU - Raman, Venkatesh K AU - Raval, Amish N AU - Guttman, Michael A AU - Thompson, Richard B AU - Ozturk, Cengizhan AU - Peters, Dana C AU - Stine, Annette M AU - Wright, Victor J AU - Schenke, William H AU - Lederman, Robert J AD - Cardiovascular Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 265 EP - 274 VL - 64 IS - 3 SN - 1522-1946, 1522-1946 KW - Index Medicus KW - Ultrasonography, Interventional KW - Iliac Artery -- diagnostic imaging KW - Feasibility Studies KW - Angiography KW - Iliac Artery -- pathology KW - Humans KW - Femoral Artery -- diagnostic imaging KW - Equipment Safety KW - Aged KW - Intraoperative Period KW - Femoral Artery -- pathology KW - Magnetic Resonance Angiography -- instrumentation KW - Radiology Department, Hospital KW - Operating Rooms KW - Intermittent Claudication -- diagnosis KW - Angioplasty, Balloon KW - Intermittent Claudication -- therapy KW - Magnetic Resonance Angiography -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67477527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Catheterization+and+cardiovascular+interventions+%3A+official+journal+of+the+Society+for+Cardiac+Angiography+%26+Interventions&rft.atitle=Invasive+human+magnetic+resonance+imaging%3A+feasibility+during+revascularization+in+a+combined+XMR+suite.&rft.au=Dick%2C+Alexander+J%3BRaman%2C+Venkatesh+K%3BRaval%2C+Amish+N%3BGuttman%2C+Michael+A%3BThompson%2C+Richard+B%3BOzturk%2C+Cengizhan%3BPeters%2C+Dana+C%3BStine%2C+Annette+M%3BWright%2C+Victor+J%3BSchenke%2C+William+H%3BLederman%2C+Robert+J&rft.aulast=Dick&rft.aufirst=Alexander&rft.date=2005-03-01&rft.volume=64&rft.issue=3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Catheterization+and+cardiovascular+interventions+%3A+official+journal+of+the+Society+for+Cardiac+Angiography+%26+Interventions&rft.issn=15221946&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-07 N1 - Date created - 2005-03-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cardiovasc Magn Reson. 2002;4(4):431-42 [12549231] Phys Med Biol. 2003 Jul 21;48(14):R37-64 [12894968] J Vasc Interv Radiol. 2003 Oct;14(10):1317-27 [14551280] Circulation. 2003 Dec 9;108(23):2899-904 [14656911] Lancet. 2003 Dec 6;362(9399):1877-82 [14667742] Magn Reson Med. 2004 Apr;51(4):668-75 [15065238] J Magn Reson Imaging. 1998 Jan-Feb;8(1):220-5 [9500284] J Magn Reson Imaging. 1998 Jan-Feb;8(1):226-34 [9500285] J Magn Reson Imaging. 1998 Nov-Dec;8(6):1338-42 [9848749] Radiology. 1999 Sep;212(3):876-84 [10478260] J Am Coll Cardiol. 2005 Jun 21;45(12):2069-77 [15963411] Magn Reson Med. 2003 Feb;49(2):216-22 [12541240] Circulation. 2003 Jan 7;107(1):132-8 [12515755] Circulation. 2002 Jul 23;106(4):511-5 [12135954] Med Sci Monit. 2002 Jul;8(7):MT113-7 [12118208] Circulation. 2002 Mar 19;105(11):1282-4 [11901036] Circulation. 2002 Feb 19;105(7):874-9 [11854130] Magn Reson Med. 2002 Jan;47(1):187-93 [11754458] J Magn Reson Imaging. 2001 Jul;14(1):56-62 [11436215] J Magn Reson Imaging. 2001 Jan;13(1):105-14 [11169811] Int J Epidemiol. 2000 Jun;29(3):424-8 [10869313] J Magn Reson Imaging. 2003 May;17(5):615-9 [12720273] Magn Reson Med. 2003 Aug;50(2):383-90 [12876715] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prediction and prevention of transplant-related mortality from pulmonary causes after total body irradiation and allogeneic stem cell transplantation. AN - 67476492; 15744241 AB - Between July 1997 and August 2004, 146 consecutive patients with hematologic malignancies received a T cell-depleted peripheral blood stem cell transplant from an HLA-identical sibling by using total body irradiation (TBI) and cyclophosphamide conditioning regimens. Eighty-five patients received 13.6 Gy of TBI with no lung shielding, and 61 received lung shielding (total lung dose, 6-12 Gy). Ninety-four patients (65.5%) had standard-risk disease; the remainder had more advanced disease or unfavorable diagnoses. Of the 21 transplant-related deaths, 14 were from pulmonary causes (10 idiopathic pulmonary syndromes and 4 from infection) that occurred at a median of 90 days (range, 23-238 days) after transplantation. Independent risk factors for pulmonary transplant-related mortality (PTRM) were pretransplantation diffusion capacity for carbon monoxide (relative risk, 5.7 for diffusion capacity for carbon monoxide <85%), smoking (relative risk, 5.0), and CD34 cell dose (relative risk, 9.4 for a CD34 dose of <5 x 10(6) cells per kilogram). Patients receiving lung shielding had significantly lower PTRM (3.3% versus 14.1%; P = .02) and better overall survival (70% +/- 6% versus 52% +/- 5%; P = .04), but lung shielding was not a significant independent factor for determining PTRM. These results suggest that pulmonary mortality after TBI-based preparative regimens is predictable and that higher CD34 cell doses can reduce the risk. JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation AU - Savani, Bipin N AU - Montero, Aldemar AU - Wu, Colin AU - Nlonda, Nene AU - Read, Elizabeth AU - Dunbar, Cynthia AU - Childs, Richard AU - Solomon, Scott AU - Barrett, A John AD - Stem Cell Allotransplant Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 223 EP - 230 VL - 11 IS - 3 SN - 1083-8791, 1083-8791 KW - Antigens, CD34 KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Humans KW - Retrospective Studies KW - Pneumonia, Pneumococcal KW - Prognosis KW - Child KW - Transplantation, Homologous KW - Transplantation Conditioning -- adverse effects KW - Cyclophosphamide -- therapeutic use KW - Risk Factors KW - Transplantation Conditioning -- methods KW - Adult KW - Follow-Up Studies KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Lung Diseases -- etiology KW - Whole-Body Irradiation -- mortality KW - Whole-Body Irradiation -- methods KW - Hematopoietic Stem Cell Transplantation -- mortality KW - Whole-Body Irradiation -- adverse effects KW - Lung Diseases -- mortality KW - Lung Diseases -- prevention & control KW - Hematopoietic Stem Cell Transplantation -- methods KW - Hematopoietic Stem Cell Transplantation -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67476492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.atitle=Prediction+and+prevention+of+transplant-related+mortality+from+pulmonary+causes+after+total+body+irradiation+and+allogeneic+stem+cell+transplantation.&rft.au=Savani%2C+Bipin+N%3BMontero%2C+Aldemar%3BWu%2C+Colin%3BNlonda%2C+Nene%3BRead%2C+Elizabeth%3BDunbar%2C+Cynthia%3BChilds%2C+Richard%3BSolomon%2C+Scott%3BBarrett%2C+A+John&rft.aulast=Savani&rft.aufirst=Bipin&rft.date=2005-03-01&rft.volume=11&rft.issue=3&rft.spage=223&rft.isbn=&rft.btitle=&rft.title=Biology+of+blood+and+marrow+transplantation+%3A+journal+of+the+American+Society+for+Blood+and+Marrow+Transplantation&rft.issn=10838791&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-22 N1 - Date created - 2005-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Integrase inhibitors to treat HIV/AIDS. AN - 67476071; 15729361 AB - HIV integrase is a rational target for treating HIV infection and preventing AIDS. It took approximately 12 years to develop clinically usable inhibitors of integrase, and Phase I clinical trials of integrase inhibitors have just begun. This review focuses on the molecular basis and rationale for developing integrase inhibitors. The main classes of lead compounds are also described, as well as the concept of interfacial inhibitors of protein-nucleic-acid interactions that might apply to the clinically used strand-transfer inhibitors. JF - Nature reviews. Drug discovery AU - Pommier, Yves AU - Johnson, Allison A AU - Marchand, Christophe AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 236 EP - 248 VL - 4 IS - 3 SN - 1474-1776, 1474-1776 KW - HIV Integrase Inhibitors KW - 0 KW - Index Medicus KW - United States KW - Antiretroviral Therapy, Highly Active -- adverse effects KW - United States Food and Drug Administration KW - Africa South of the Sahara -- epidemiology KW - Humans KW - Drug Approval KW - Mutation KW - Structure-Activity Relationship KW - HIV Integrase Inhibitors -- therapeutic use KW - HIV -- physiology KW - Virus Replication -- drug effects KW - HIV Integrase Inhibitors -- chemistry KW - HIV Infections -- drug therapy KW - HIV Infections -- mortality KW - Virus Replication -- physiology KW - HIV Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67476071?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Drug+discovery&rft.atitle=Integrase+inhibitors+to+treat+HIV%2FAIDS.&rft.au=Pommier%2C+Yves%3BJohnson%2C+Allison+A%3BMarchand%2C+Christophe&rft.aulast=Pommier&rft.aufirst=Yves&rft.date=2005-03-01&rft.volume=4&rft.issue=3&rft.spage=236&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Drug+discovery&rft.issn=14741776&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-01 N1 - Date created - 2005-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The promise of genetically engineered mice for cancer prevention studies. AN - 67475504; 15738982 AB - Sophisticated genetic technologies have led to the development of mouse models of human cancers that recapitulate important features of human oncogenesis. Many of these genetically engineered mouse models promise to be very relevant and relatively rapid systems for determining the efficacy of chemopreventive agents and their mechanisms of action. The validation of such models for chemoprevention will help the selection of appropriate agents for large-scale clinical trials and allow the testing of combination therapies. JF - Nature reviews. Cancer AU - Green, Jeffrey E AU - Hudson, Tamaro AD - Transgenic Oncogenesis Group, Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Besthesda, MD 20892, USA. jegreen@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 184 EP - 198 VL - 5 IS - 3 SN - 1474-175X, 1474-175X KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Animals KW - Colonic Neoplasms -- genetics KW - Humans KW - Colonic Neoplasms -- veterinary KW - Mammary Neoplasms, Experimental -- genetics KW - Mice KW - Antineoplastic Agents -- pharmacology KW - Disease Models, Animal KW - Neoplasms -- prevention & control KW - Chemoprevention KW - Animals, Genetically Modified KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67475504?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+reviews.+Cancer&rft.atitle=The+promise+of+genetically+engineered+mice+for+cancer+prevention+studies.&rft.au=Green%2C+Jeffrey+E%3BHudson%2C+Tamaro&rft.aulast=Green&rft.aufirst=Jeffrey&rft.date=2005-03-01&rft.volume=5&rft.issue=3&rft.spage=184&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 - 2005-03-22 N1 - Date created - 2005-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New science-based endpoints to accelerate oncology drug development. AN - 67473871; 15737552 AB - Although several new oncology drugs have reached the market, more than 80% of drugs for all indications entering clinical development do not get marketing approval, with many failing late in development often in Phase III trials, because of unexpected safety issues or difficulty determining efficacy, including confounded outcomes. These factors contribute to the high costs of oncology drug development and clearly show the need for faster, more cost-effective strategies for evaluating oncology drugs and better definition of patients who will benefit from treatment. Remarkable advances in the understanding of neoplastic progression at the cellular and molecular levels have spurred the discovery of molecularly targeted drugs. This progress along with advances in imaging and bioassay technologies are the basis for describing and evaluating new biomarker endpoints as well as for defining other biomarkers for identifying patient populations, potential toxicity, and providing evidence of drug effect and efficacy. Definitions and classifications of these biomarkers for use in oncology drug development are presented in this paper. Science-based and practical criteria for validating biomarkers have been developed including considerations of mechanistic plausibility, available methods and technology, and clinical feasibility. New promising tools for measuring biomarkers have also been developed and are based on genomics and proteomics, direct visualisation by microscopy (e.g., confocal microscopy and computer-assisted image analysis of cellular features), nanotechnologies, and direct and remote imaging (e.g., fluorescence endoscopy and anatomical, functional and molecular imaging techniques). The identification and evaluation of potential surrogate endpoints and other biomarkers require access to and analysis of large amounts of data, new technologies and extensive research resources. Further, there is a requirement for a convergence of research, regulatory and drug developer thinking - an effort that will not be accomplished by individual scientists or research institutions. Research collaborations are needed to foster development of these new endpoints and other biomarkers and, in the United States (US), include ongoing efforts among the Food and Drug Administration (FDA), National Cancer Institute (NCI), academia, and industry. JF - European journal of cancer (Oxford, England : 1990) AU - Kelloff, Gary J AU - Sigman, Caroline C AD - Division of Cancer Treatment and Diagnosis, Cancer Imaging Program, National Cancer Institute, Executive Plaza North Room 6038, 9000 Rockville Pike, Bethesda, MD 20892, USA. kelloffg@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 491 EP - 501 VL - 41 IS - 4 SN - 0959-8049, 0959-8049 KW - Antineoplastic Agents KW - 0 KW - Biomarkers, Tumor KW - Index Medicus KW - Costs and Cost Analysis KW - Humans KW - Prognosis KW - Biomarkers, Tumor -- analysis KW - Forecasting KW - Neoplasms -- drug therapy KW - Antineoplastic Agents -- economics KW - Antineoplastic Agents -- therapeutic use KW - Drug Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67473871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=New+science-based+endpoints+to+accelerate+oncology+drug+development.&rft.au=Kelloff%2C+Gary+J%3BSigman%2C+Caroline+C&rft.aulast=Kelloff&rft.aufirst=Gary&rft.date=2005-03-01&rft.volume=41&rft.issue=4&rft.spage=491&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 - 2005-05-03 N1 - Date created - 2005-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of a functional polymorphism in the serotonin transporter gene with abnormal emotional processing in ecstasy users. AN - 67473793; 15741482 AB - The long-term effects of the use of 3,4-methylenedioxymethamphetamine (MDMA, or Ecstasy) in humans are controversial and unclear. The authors' goal was to assess the contribution of a functional polymorphism in the gene encoding serotonin transporter to changes in emotional processing following chronic Ecstasy use. They investigated Beck Depression Inventory scores and performance on the Affective Go/No-Go test, a computerized neuropsychological test sensitive to emotional processing, in Ecstasy users and comparison subjects, stratifying the results by serotonin transporter genotype. Ecstasy use was associated with higher Beck Depression Inventory score and abnormalities in the Affective Go/No-Go test in individuals with the ss and ls genotype but not those with the ll genotype. Ecstasy users carrying the s allele, but not comparison subjects carrying the s allele, showed abnormal emotional processing. On the basis of a comparison with acute tryptophan depletion, the authors hypothesize that chronic Ecstasy use may cause long-term changes to the serotonin system, and that Ecstasy users carrying the s allele may be at particular risk for emotional dysfunction. JF - The American journal of psychiatry AU - Roiser, Jonathan P AU - Cook, Lynnette J AU - Cooper, Jason D AU - Rubinsztein, David C AU - Sahakian, Barbara J AD - Department of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrooke,s Hospital, Cambridge CB2 2QQ, UK. roiserj@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 609 EP - 612 VL - 162 IS - 3 SN - 0002-953X, 0002-953X KW - Membrane Glycoproteins KW - 0 KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - SLC6A4 protein, human KW - Serotonin Plasma Membrane Transport Proteins KW - Tryptophan KW - 8DUH1N11BX KW - N-Methyl-3,4-methylenedioxyamphetamine KW - KE1SEN21RM KW - Abridged Index Medicus KW - Index Medicus KW - Genotype KW - Humans KW - Adult KW - Diagnosis, Dual (Psychiatry) KW - Depressive Disorder -- diagnosis KW - Depressive Disorder -- genetics KW - Personality Inventory KW - Tryptophan -- deficiency KW - Neuropsychological Tests KW - Male KW - Female KW - Substance-Related Disorders -- physiopathology KW - Affective Symptoms -- physiopathology KW - Nerve Tissue Proteins -- physiology KW - Affective Symptoms -- diagnosis KW - N-Methyl-3,4-methylenedioxyamphetamine -- adverse effects KW - Membrane Glycoproteins -- physiology KW - Polymorphism, Genetic -- genetics KW - Affective Symptoms -- genetics KW - Membrane Transport Proteins -- physiology KW - Nerve Tissue Proteins -- genetics KW - Substance-Related Disorders -- diagnosis KW - Polymorphism, Genetic -- physiology KW - Membrane Transport Proteins -- genetics KW - Substance-Related Disorders -- genetics KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67473793?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Association+of+a+functional+polymorphism+in+the+serotonin+transporter+gene+with+abnormal+emotional+processing+in+ecstasy+users.&rft.au=Roiser%2C+Jonathan+P%3BCook%2C+Lynnette+J%3BCooper%2C+Jason+D%3BRubinsztein%2C+David+C%3BSahakian%2C+Barbara+J&rft.aulast=Roiser&rft.aufirst=Jonathan&rft.date=2005-03-01&rft.volume=162&rft.issue=3&rft.spage=609&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 - 2005-04-22 N1 - Date created - 2005-03-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Psychol Med. 1999 Nov;29(6):1307-21 [10616937] Neurology. 2000 Jul 25;55(2):294-6 [10908909] Psychopharmacology (Berl). 2001 Mar;154(3):319-26 [11351939] Neuroscience. 2002;110(1):41-8 [11882371] Lancet. 2001 Dec 1;358(9296):1864-9 [11741626] J Psychopharmacol. 2001 Sep;15(3):181-6 [11565625] Arch Gen Psychiatry. 2002 Jul;59(7):597-604 [12090812] J Psychopharmacol. 2002 Mar;16(1):103 [11949766] Arch Gen Psychiatry. 2002 Jul;59(7):613-20 [12090814] Psychopharmacology (Berl). 2002 Aug;163(1):42-53 [12185399] Pharmacol Rev. 2003 Sep;55(3):463-508 [12869661] Psychopharmacology (Berl). 2004 Jan;171(3):286-97 [12955284] Science. 1996 Nov 29;274(5292):1527-31 [8929413] Am J Med Genet. 1998 Feb 7;81(1):58-63 [9514589] Neuropsychopharmacology. 1998 Jul;19(1):26-35 [9608574] Mol Psychiatry. 1998 Nov;3(6):508-11 [9857976] Arch Gen Psychiatry. 1961 Jun;4:561-71 [13688369] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Electroporation loading of calcium-sensitive dyes into the CNS. AN - 67471573; 15509647 AB - Calcium imaging of neural network function has been limited by the extent of tissue labeled or the time taken for labeling. We now describe the use of electroporation-an established technique for transfecting cells with genes-to load neurons with calcium-sensitive dyes in the isolated spinal cord of the neonatal mouse in vitro. The dyes were injected subdurally, intravascularly, or into the central canal. This technique results in rapid and extensive labeling of neurons and their processes at all depths of the spinal cord, over a rostrocaudal extent determined by the position and size of the electrodes. Our results suggest that vascular distribution of the dye is involved in all three types of injections. Electroporation disrupts local reflex and network function only transiently (approximately 1 h), after which time they recover. We describe applications of the method to image activity of neuronal populations and individual neurons during antidromic, reflex, and locomotor-like behaviors. We show that these different motor behaviors are characterized by distinct patterns of activation among the labeled populations of cells. JF - Journal of neurophysiology AU - Bonnot, Agnès AU - Mentis, George Z AU - Skoch, Jesse AU - O'Donovan, Michael J AD - Laboratory of Neural Control, Section on Developmental Neurobiology, NINDS, National Institutes of Health, 35 Convent Dr., Rm. 3C1010, Bethesda, MD 20892, USA. bonnota@ninds.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 1793 EP - 1808 VL - 93 IS - 3 SN - 0022-3077, 0022-3077 KW - Fluorescent Dyes KW - 0 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Microinjections -- methods KW - Electric Stimulation -- methods KW - Staining and Labeling -- methods KW - Membrane Potentials -- physiology KW - Mice KW - Dose-Response Relationship, Radiation KW - Cell Survival KW - Diagnostic Imaging -- methods KW - Animals, Newborn KW - Calcium Signaling -- physiology KW - Electrophysiology -- methods KW - In Vitro Techniques KW - Time Factors KW - Calcium -- metabolism KW - Fluorescent Dyes -- metabolism KW - Neurons -- metabolism KW - Electroporation KW - Neurons -- classification KW - Spinal Cord -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67471573?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Electroporation+loading+of+calcium-sensitive+dyes+into+the+CNS.&rft.au=Bonnot%2C+Agn%C3%A8s%3BMentis%2C+George+Z%3BSkoch%2C+Jesse%3BO%27Donovan%2C+Michael+J&rft.aulast=Bonnot&rft.aufirst=Agn%C3%A8s&rft.date=2005-03-01&rft.volume=93&rft.issue=3&rft.spage=1793&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-02 N1 - Date created - 2005-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular epidemiology of HIV-1 subtypes in southern China. AN - 67465594; 15735457 AB - The driving forces of the HIV-1 epidemic in Guangxi, China were assessed by investigating virologic and epidemiologic data from a cohort of longitudinally followed injection drug users (IDUs) in Binyang and Pingxiang, major urban areas along 2 separate drug routes in the province. Sera and interview data were obtained in September and October of 2000. Sequence analysis of HIV-1 was performed on the gag-pol region (HXB2 nt 1850-3005) and C2 to V4 env (HXB2 nt 6704-7626). Sequence data demonstrated that 88% of the infections in Pingxiang were CRF01_AE, whereas 96% in Bin-yang were CRF08_BC. Three recently infected subjects in Pingxiang were infected with CRF08_BC, and 1 chronically infected subject had evidence of a recombinant virus. Intersubject distances were statistically greater for CRF01_AE-infected subjects than CRF08_BC-infected subjects for all regions except V4. The epidemic in Binyang is similar to previously described IDU-based epidemics, with a strong founder effect with little variation in V3. The epidemic in Pingxiang may have had multiple introductions of the CRF01_AE epidemic into the city and greater spread through sexual transmission, resulting in greater variation in V3 than typically seen in purely parenterally based epidemics. JF - Journal of acquired immune deficiency syndromes (1999) AU - Laeyendecker, Oliver AU - Zhang, Guang Wen AU - Quinn, Thomas C AU - Garten, Rebecca AU - Ray, Stuart C AU - Lai, Shenghan AU - Liu, Wei AU - Chen, Jie AU - Yu, Xiao-Fang AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 2005/03/01/ PY - 2005 DA - 2005 Mar 01 SP - 356 EP - 362 VL - 38 IS - 3 SN - 1525-4135, 1525-4135 KW - DNA, Complementary KW - 0 KW - DNA, Viral KW - Fusion Proteins, gag-pol KW - Gene Products, env KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Genes, pol KW - HIV Reverse Transcriptase -- genetics KW - Sequence Alignment KW - Molecular Epidemiology KW - Genes, env KW - Adult KW - Molecular Sequence Data KW - Urban Population KW - Genes, gag KW - Male KW - Gene Products, env -- chemistry KW - Phylogeny KW - HIV Protease -- genetics KW - Fusion Proteins, gag-pol -- genetics KW - Amino Acid Sequence KW - HIV Reverse Transcriptase -- chemistry KW - HIV Protease -- chemistry KW - Sequence Analysis, DNA KW - DNA, Viral -- chemistry KW - China -- epidemiology KW - DNA, Viral -- isolation & purification KW - Middle Aged KW - Substance Abuse, Intravenous -- complications KW - Female KW - HIV-1 -- genetics KW - HIV Infections -- virology KW - HIV-1 -- isolation & purification KW - HIV Infections -- epidemiology KW - HIV-1 -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67465594?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Molecular+epidemiology+of+HIV-1+subtypes+in+southern+China.&rft.au=Laeyendecker%2C+Oliver%3BZhang%2C+Guang+Wen%3BQuinn%2C+Thomas+C%3BGarten%2C+Rebecca%3BRay%2C+Stuart+C%3BLai%2C+Shenghan%3BLiu%2C+Wei%3BChen%2C+Jie%3BYu%2C+Xiao-Fang&rft.aulast=Laeyendecker&rft.aufirst=Oliver&rft.date=2005-03-01&rft.volume=38&rft.issue=3&rft.spage=356&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 - 2005-04-12 N1 - Date created - 2005-02-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AY635760; GENBANK; AY635761; AY635762; AY635722; AY635721; AY635720; AY635726; AY635725; AY635724; AY635723; AY635729; AY635728; AY635727; AY635731; AY635730; AY635733; AY635732; AY635735; AY635734; AY635737; AY635736; AY635739; AY635738; AY635749; AY635745; AY635746; AY635747; AY635748; AY635741; AY635742; AY635743; AY635744; AY635740; AY635700; AY635708; AY635707; AY635706; AY635705; AY635704; AY635703; AY635702; AY635701; AY635758; AY635709; AY635691; AY635759; AY635692; AY635756; AY635757; AY635754; AY635755; AY635752; AY635753; AY635750; AY635751; AY635711; AY635710; AY635696; AY635717; AY635695; AY635716; AY635694; AY635719; AY635693; AY635718; AY635713; AY635712; AY635699; AY635715; AY635698; AY635714; AY635697 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recovery from DSM-IV alcohol dependence: United States, 2001-2002. AN - 67465065; 15733237 AB - To investigate the prevalence and correlates of recovery from Diagnostic and Statistical Manual version IV (DSM-IV) alcohol dependence by examining the past-year status of individuals who met the criteria for prior-to-past-year (PPY) dependence. Cross-sectional, retrospective survey of a nationally representative sample of US adults 18 years of age and over (first wave of a planned longitudinal survey). This analysis is based on data from the 2001-02 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), in which data were collected in personal interviews conducted with one randomly selected adult in each sample household. A subset of the NESARC sample (total n = 43 093), consisting of 4422 US adults 18 years of age and over classified with PPY DSM-IV alcohol dependence, were evaluated with respect to their past-year recovery status: past-year dependence, partial remission, full remission, asymptomatic risk drinking, abstinent recovery (AR) and non-abstinent recovery (NR). Correlates of past-year status were examined in bivariate analyses and using multivariate logistic regression models. Of people classified with PPY alcohol dependence, 25.0% were still classified as dependent in the past year; 27.3% were classified as being in partial remission; 11.8% were asymptomatic risk drinkers who demonstrated a pattern of drinking that put them at risk of relapse; 17.7% were low-risk drinkers; and 18.2% were abstainers. Only 25.5% of people with PPY dependence ever received treatment. Being married was associated positively with the odds of both AR and NR, and ethanol intake was negatively associated with both. Severity of dependence increased the odds of AR but decreased the odds of NR. The odds of AR (but not NR) increased with age and female gender but were decreased by the presence of a personality disorder. Treatment history modified the effects of college attendance/graduation, age at onset and interval since onset on the odds of recovery. There is a substantial level of recovery from alcohol dependence. Information on factors associated with recovery may be useful in targeting appropriate treatment modalities. JF - Addiction (Abingdon, England) AU - Dawson, Deborah A AU - Grant, Bridget F AU - Stinson, Frederick S AU - Chou, Patricia S AU - Huang, Boji AU - Ruan, W June AD - Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. ddawson@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 281 EP - 292 VL - 100 IS - 3 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Epidemiologic Methods KW - Humans KW - Aged KW - Recurrence KW - Remission, Spontaneous KW - Adult KW - Middle Aged KW - Adolescent KW - United States -- epidemiology KW - Temperance -- statistics & numerical data KW - Diagnostic and Statistical Manual of Mental Disorders KW - Female KW - Male KW - Alcoholism -- rehabilitation KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67465065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recovery+from+DSM-IV+alcohol+dependence%3A+United+States%2C+2001-2002.&rft.au=Dawson%2C+Deborah+A%3BGrant%2C+Bridget+F%3BStinson%2C+Frederick+S%3BChou%2C+Patricia+S%3BHuang%2C+Boji%3BRuan%2C+W+June&rft.aulast=Dawson&rft.aufirst=Deborah&rft.date=2005-03-01&rft.volume=100&rft.issue=3&rft.spage=281&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 - 2005-06-07 N1 - Date created - 2005-02-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Addiction. 2005 Mar;100(3):294; discussion 296-8 [15733239] Addiction. 2005 Mar;100(3):295-6; discussion 296-8 [15733241] Addiction. 2005 Mar;100(3):294-5; discussion 296-8 [15733240] Addiction. 2005 Mar;100(3):293; discussion 296-8 [15733238] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retrospective analyses of pooled data from CREST I and CREST II trials for treatment of cocaine dependence. AN - 67460135; 15730353 AB - To analyze pooled data from the Cocaine Rapid Evaluation Screening Trial (CREST). Pooling data from these small pilot trials into four major drug classes permitted data exploration for treatment and covariate effects with increased sample size. Small pilot trials were conducted to screen fifteen medications as prospective treatments for cocaine dependence. Studies included a flexible 2-week to 4-week screening/baseline period followed by an 8-week randomized treatment condition. Participants were randomized equally to one of up to three active medications or placebo. Five Medications Development Research Units at the five academic centers of University of Cincinnati, New York University, University of Pennsylvania, University of California Los Angeles and Boston University. The pooled data set consisted of 357 total subjects. Standardized inclusion and exclusion criteria were employed in subject selection to enhance consistency of cocaine-dependent study participants across all sites (see reports on individual trials in this supplement for details). All participants provided at least two urine samples that were positive for cocaine metabolite during a two-week period prior to being randomized. All subjects in these trials, those randomized to placebo and active medications, received active treatment in the form of evidence-based cognitive behavioral therapy. Quantitative urine benzoylecgonine (BE), self-report of cocaine use, and total Brief Substance Craving Scale (BSCS) scores were compared between each class of medication and its matched-placebo group. Regression analysis of pooled data did not identify any statistically significant differences between treatment and matched-placebo for any of the four classes. Exploration of the effects of baseline covariates indicated that gender and African American status were associated significantly with outcome. Female gender was consistently associated with poorer outcomes for medication and placebo groups, while the direction of association between African American status and outcome differed by treatment groups. Retention was also examined: dropout rates may have been somewhat higher for placebo than treatment groups during the early active-treatment period. Classification trees were used to identify characteristics of subjects who were abstinent for at least two weeks during the eight-week trial; only 4.0% of females while 17.9% of males achieved this criterion. Results presented here may prove useful for planning future clinical trials for therapies targeting cocaine dependence. JF - Addiction (Abingdon, England) AU - Elkashef, Ahmed AU - Holmes, Tyson H AU - Bloch, Daniel A AU - Shoptaw, Steve AU - Kampman, Kyle AU - Reid, Malcolm S AU - Somoza, Eugene AU - Ciraulo, Domenic AU - Rotrosen, John AU - Leiderman, Deborah AU - Montgomery, Ann AU - Vocci, Frank AD - Division of Pharmacotherapies and Medical Consequences of Drug Abuse, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 91 EP - 101 VL - 100 Suppl 1 SN - 0965-2140, 0965-2140 KW - Central Nervous System Agents KW - 0 KW - Dopamine Agonists KW - Placebos KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Logistic Models KW - Humans KW - Retrospective Studies KW - Clinical Trials as Topic KW - Pilot Projects KW - Male KW - Female KW - Dopamine Agonists -- therapeutic use KW - Cocaine-Related Disorders -- drug therapy KW - Central Nervous System Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67460135?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Retrospective+analyses+of+pooled+data+from+CREST+I+and+CREST+II+trials+for+treatment+of+cocaine+dependence.&rft.au=Elkashef%2C+Ahmed%3BHolmes%2C+Tyson+H%3BBloch%2C+Daniel+A%3BShoptaw%2C+Steve%3BKampman%2C+Kyle%3BReid%2C+Malcolm+S%3BSomoza%2C+Eugene%3BCiraulo%2C+Domenic%3BRotrosen%2C+John%3BLeiderman%2C+Deborah%3BMontgomery%2C+Ann%3BVocci%2C+Frank&rft.aulast=Elkashef&rft.aufirst=Ahmed&rft.date=2005-03-01&rft.volume=100+Suppl+1&rft.issue=&rft.spage=91&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 - 2005-06-23 N1 - Date created - 2005-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polymorphisms in XPD and TP53 and mutation in human lung cancer. AN - 67455681; 15564288 AB - The pattern of somatic mutations in TP53 is distinct for particular cancers and carcinogenic exposures, providing clues to disease etiology, e.g. G:C-->T:A mutations in TP53 are more frequently observed in smoking-associated lung cancers. In order to investigate possible causes and mechanisms of lung cancer susceptibility differences, the TP53 gene was sequenced in a case-only study of lung cancers (206 men and 103 women). Our primary hypothesis was that the TP53 mutation spectrum is influenced by polymorphisms in genes involved in DNA repair and apoptosis. We observed a TP53 mutation frequency in exons 5-8 of 25%. Functional polymorphisms in XPD (Asp312Asn, rs1799793 and Lys751Gln, rs1052559), a protein required for nucleotide excision repair and with roles in p53-mediated apoptosis, were modestly associated with G:C-->T:A mutations in TP53 in lung tumors [Asp/Asn312 + Asn/Asn312 and/or Lys/Gln751 + Gln/Gln751 versus Asp/Asp312 + Lys/Lys751; odds ratio (OR) 2.73, 95% confidence interval (CI) 0.98-7.61], consistent with the role of this protein in repair of bulky carcinogen-DNA adducts. In addition, a TP53 polymorphism (Arg72Pro, rs1042522) with a known role in the efficiency of apoptosis was also associated with the presence of a TP53 mutation (Pro/Arg72 or Pro/Pro72 versus Arg/Arg72; OR 2.25, 95% CI 1.21-4.17) or a G:C-->T:A mutation in TP53 (Pro/Arg72 or Pro/Pro72 versus Arg/Arg72; OR 2.42, 95% CI 0.97-6.04). An interaction between the XPD variant alleles (Asn312 and Gln751) and the TP53 Pro72 allele was observed for TP53 mutations (any TP53 mutation P(int) = 0.027, G:C-->T:A TP53 mutation P(int) = 0.041). The statistical interaction observed in our study is consistent with the observed biological interaction for XPD and p53 in nucleotide excision repair and apoptosis. In conclusion, differences in TP53 mutation spectra in lung tumors are associated with several genetic factors and may reflect differences in lung cancer susceptibility and carcinogenesis. JF - Carcinogenesis AU - Mechanic, Leah E AU - Marrogi, Aizen J AU - Welsh, Judith A AU - Bowman, Elise D AU - Khan, Mohammed A AU - Enewold, Lindsey AU - Zheng, Yun-Ling AU - Chanock, Stephen AU - Shields, Peter G AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, NCI Center for Cancer Research, 37 Convent Drive, Bethesda, MD 20892-4255, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 597 EP - 604 VL - 26 IS - 3 SN - 0143-3334, 0143-3334 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Transcription Factors KW - DNA Helicases KW - EC 3.6.4.- KW - Xeroderma Pigmentosum Group D Protein KW - EC 3.6.4.12 KW - ERCC2 protein, human KW - EC 5.99.- KW - Index Medicus KW - Base Sequence KW - Humans KW - Male KW - Female KW - Genes, p53 KW - Polymorphism, Genetic KW - DNA-Binding Proteins -- genetics KW - DNA Helicases -- genetics KW - Lung Neoplasms -- genetics KW - Transcription Factors -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67455681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Polymorphisms+in+XPD+and+TP53+and+mutation+in+human+lung+cancer.&rft.au=Mechanic%2C+Leah+E%3BMarrogi%2C+Aizen+J%3BWelsh%2C+Judith+A%3BBowman%2C+Elise+D%3BKhan%2C+Mohammed+A%3BEnewold%2C+Lindsey%3BZheng%2C+Yun-Ling%3BChanock%2C+Stephen%3BShields%2C+Peter+G%3BHarris%2C+Curtis+C&rft.aulast=Mechanic&rft.aufirst=Leah&rft.date=2005-03-01&rft.volume=26&rft.issue=3&rft.spage=597&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-13 N1 - Date created - 2005-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modeling metastasis in vivo. AN - 67454795; 15358632 AB - Metastasis, the spread of a tumor from its primary site to other parts of the body, continues to be the most significant problem in the field of cancer. Patients who present with metastatic disease or those who develop metastases after successful management of the primary tumor carry a universally grave prognosis. To improve treatment outcomes for these patients a broader understanding of the biology of metastases is necessary. The biological complexity that characterizes metastasis requires complex experimental systems for its study. To a large extent the modeling of this biological complexity is only possible using animal models. The following review will summarize the strengths and weaknesses of available in vivo models of metastasis including transplantable syngeneic mouse and human-mouse xenografts, genetically engineered mice and naturally occurring cancers of companion animals (pet dogs and cats). No single metastasis model is sufficient to answer all questions. As such, the selection of the optimal model(s) for each biological or translational question is necessary. JF - Carcinogenesis AU - Khanna, Chand AU - Hunter, Kent AD - Comparative Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. khannac@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 513 EP - 523 VL - 26 IS - 3 SN - 0143-3334, 0143-3334 KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Humans KW - Neoplasm Metastasis KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67454795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Modeling+metastasis+in+vivo.&rft.au=Khanna%2C+Chand%3BHunter%2C+Kent&rft.aulast=Khanna&rft.aufirst=Chand&rft.date=2005-03-01&rft.volume=26&rft.issue=3&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-13 N1 - Date created - 2005-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cutting edge: p27Kip1 deficiency reduces the requirement for CD28-mediated costimulation in naive CD8+ but not CD4+ T lymphocytes. AN - 67454313; 15728451 AB - Cell cycle re-entry of quiescent T cells is dependent upon cyclin-dependent kinase 2. Inhibition of cyclin-dependent kinase 2 by p27(Kip1) is believed to be the principal constraint on S-phase entry in T cells. We report that deficiency for p27(Kip1) has a more pronounced effect on the expansion of murine naive CD8(+) T cells and that this disparity is due to a reduced requirement for CD28-mediated costimulation in CD8(+) but not CD4(+) T cells lacking p27(Kip1). These data highlight a previously unappreciated difference in the way CD28 signaling is coupled to the core cell cycle machinery in these two T cell subsets. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Wolfraim, Lawrence A AU - Letterio, John J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. wolfraim@tolergenics.com Y1 - 2005/03/01/ PY - 2005 DA - 2005 Mar 01 SP - 2481 EP - 2484 VL - 174 IS - 5 SN - 0022-1767, 0022-1767 KW - Antigens, CD28 KW - 0 KW - Cdkn1a protein, mouse KW - Cdkn1b protein, mouse KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Resting Phase, Cell Cycle -- immunology KW - Mice KW - CD4-CD8 Ratio KW - Cell Proliferation KW - Resting Phase, Cell Cycle -- genetics KW - Mice, Knockout KW - Cells, Cultured KW - Kinetics KW - Signal Transduction -- genetics KW - Mice, Inbred C57BL KW - Signal Transduction -- immunology KW - Female KW - Male KW - Tumor Suppressor Proteins -- deficiency KW - CD4-Positive T-Lymphocytes -- cytology KW - CD8-Positive T-Lymphocytes -- metabolism KW - Cell Cycle Proteins -- biosynthesis KW - Antigens, CD28 -- physiology KW - Tumor Suppressor Proteins -- genetics KW - CD4-Positive T-Lymphocytes -- immunology KW - Down-Regulation -- immunology KW - Tumor Suppressor Proteins -- biosynthesis KW - CD8-Positive T-Lymphocytes -- cytology KW - Antigens, CD28 -- genetics KW - Lymphocyte Activation -- genetics KW - CD4-Positive T-Lymphocytes -- metabolism KW - Cell Cycle Proteins -- genetics KW - Down-Regulation -- genetics KW - Lymphocyte Activation -- immunology KW - CD8-Positive T-Lymphocytes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67454313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Cutting+edge%3A+p27Kip1+deficiency+reduces+the+requirement+for+CD28-mediated+costimulation+in+naive+CD8%2B+but+not+CD4%2B+T+lymphocytes.&rft.au=Wolfraim%2C+Lawrence+A%3BLetterio%2C+John+J&rft.aulast=Wolfraim&rft.aufirst=Lawrence&rft.date=2005-03-01&rft.volume=174&rft.issue=5&rft.spage=2481&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 - 2005-04-19 N1 - Date created - 2005-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 4-Hydroxybutyl(butyl)nitrosamine-induced urinary bladder cancers in mice: characterization of FHIT and survivin expression and chemopreventive effects of indomethacin. AN - 67453690; 15591090 AB - The administration of 4-hydroxybutyl(butyl)nitrosamine (OH-BBN) to male B6D2F1 mice yielded a high incidence of large palpable urinary bladder cancers. Since prior studies demonstrated chemopreventive effects of non-steroidal anti-inflammatory drugs (NSAIDs), we further explored the efficacy of the NSAID indomethacin using different treatment regimens. OH-BBN was administered twice per week for 12 weeks (the first week of treatment was designated week 1). In Experiment I continual indomethacin treatment (20 mg/kg diet) was initiated either prior to (week -1) or following (week 13) OH-BBN dosing. Palpable bladder masses (subsequently diagnosed as cancers) developed in 32% of carcinogen-treated only mice by 32 weeks, while mice administered indomethacin either prior to or after OH-BBN developed palpable masses in 3 and 6% of the animals, respectively. In Experiment II mice were treated with indomethacin beginning 1 week after OH-BBN for either 12 weeks (limited treatment, weeks 13-24) or for 30 weeks (weeks 13-42). Continual treatment resulted in a 77% decrease in palpable bladder masses and an 82% decrease in all cancers (palpable and microscopic), while limited treatment decreased palpable masses by 48% but failed to decrease the number of bladder cancers (palpable plus microscopic). In Experiment III OH-BBN-treated mice were followed for 61 weeks. Palpable masses developed in 66% of control mice, while 26% of mice treated with indomethacin continually from 1 week after OH-BBN (weeks 13-61) developed palpable masses. A separate group in this study treated with indomethacin beginning when 5% of the mice had palpable bladder masses continued to develop new masses for an additional 4 weeks. By 6 weeks after beginning indomethacin treatment, however, these animals showed a profound decrease in the development of additional cancers. The expressions of FHIT and survivin in normal urinary bladder epithelium and in bladder cancers were determined by immunohistochemical analysis. FHIT was expressed at high levels in normal epithelium, but was minimally expressed in cancers, and even showed decreased expression in papillomas. The anti-apoptotic protein survivin was not expressed in normal bladder epithelium, but was variably expressed in cancers. FHIT and survivin expressions were similar in cancers from indomethacin-treated and non-treated mice. JF - Carcinogenesis AU - Lubet, Ronald A AU - Huebner, Kay AU - Fong, Louise Y Y AU - Altieri, Dario C AU - Steele, Vernon E AU - Kopelovich, Levy AU - Kavanaugh, Claudine AU - Juliana, M Margaret AU - Soong, Seng-Jaw AU - Grubbs, Clinton J AD - Division of Cancer Prevention, National Cancer Institute, Executive Plaza North, Suite 2110, 6130 Executive Boulevard, Bethesda, MD 20852, USA. rl57@nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 571 EP - 578 VL - 26 IS - 3 SN - 0143-3334, 0143-3334 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Birc5 protein, mouse KW - Carcinogens KW - Inhibitor of Apoptosis Proteins KW - Microtubule-Associated Proteins KW - Neoplasm Proteins KW - Repressor Proteins KW - fragile histidine triad protein KW - Butylhydroxybutylnitrosamine KW - 3817-11-6 KW - Acid Anhydride Hydrolases KW - EC 3.6.- KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Animals KW - Mice KW - Immunohistochemistry KW - Male KW - Butylhydroxybutylnitrosamine -- toxicity KW - Microtubule-Associated Proteins -- metabolism KW - Urinary Bladder Neoplasms -- prevention & control KW - Carcinogens -- toxicity KW - Acid Anhydride Hydrolases -- metabolism KW - Neoplasm Proteins -- metabolism KW - Urinary Bladder Neoplasms -- chemically induced KW - Indomethacin -- pharmacology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67453690?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=4-Hydroxybutyl%28butyl%29nitrosamine-induced+urinary+bladder+cancers+in+mice%3A+characterization+of+FHIT+and+survivin+expression+and+chemopreventive+effects+of+indomethacin.&rft.au=Lubet%2C+Ronald+A%3BHuebner%2C+Kay%3BFong%2C+Louise+Y+Y%3BAltieri%2C+Dario+C%3BSteele%2C+Vernon+E%3BKopelovich%2C+Levy%3BKavanaugh%2C+Claudine%3BJuliana%2C+M+Margaret%3BSoong%2C+Seng-Jaw%3BGrubbs%2C+Clinton+J&rft.aulast=Lubet&rft.aufirst=Ronald&rft.date=2005-03-01&rft.volume=26&rft.issue=3&rft.spage=571&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-13 N1 - Date created - 2005-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeting malignant B-cell lymphoma with a humanized anti-CD22 scFv-angiogenin immunoenzyme. AN - 67450248; 15725080 AB - We report on the generation and functional characterization of a humanized immunoenzyme comprising a stable humanized single chain Fv (scFv) with grafted specificity of the anti-CD22 murine monoclonal antibody RFB4 and the human ribonuclease angiogenin (ANG). The fusion protein produced from transiently transfected mammalian Chinese hamster ovary cells could easily be purified to homogeneity, retained full ribonucleolytic activity, and efficiently killed CD22(+) tumour cells with an IC(50) of 56 nmol/l. In contrast, incubation of tumour cells with either ANG or scFv alone did not result in any cytotoxicity. Potent receptor-mediated killing of target cells, expected lack of extracellular toxicity, predictable low immunogenic potential, and ease of production, suggest that this novel immunoenzyme has potential for the immunotherapy of CD22(+) malignancies. JF - British journal of haematology AU - Krauss, Jürgen AU - Arndt, Michaela A E AU - Vu, Bang K AU - Newton, Dianne L AU - Rybak, Susanna M AD - SAIC, National Cancer Institute at Frederick, Frederick, MD 21702, USA. juergen.krauss@uni-essen.de Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 602 EP - 609 VL - 128 IS - 5 SN - 0007-1048, 0007-1048 KW - Antigens, CD KW - 0 KW - Antigens, Differentiation, B-Lymphocyte KW - CD22 protein, human KW - Cell Adhesion Molecules KW - Immunoglobulin Fragments KW - Lectins KW - Recombinant Fusion Proteins KW - Sialic Acid Binding Ig-like Lectin 2 KW - angiogenin KW - EC 3.1.27.- KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Index Medicus KW - Transfection -- methods KW - Animals KW - Genetic Engineering KW - Humans KW - Cytotoxicity Tests, Immunologic KW - CHO Cells KW - Cell Line, Tumor KW - Recombinant Fusion Proteins -- therapeutic use KW - Cricetinae KW - Lymphoma, B-Cell -- therapy KW - Lymphoma, B-Cell -- immunology KW - Cell Adhesion Molecules -- immunology KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Immunization, Passive -- methods KW - Lectins -- immunology KW - Antigens, CD -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67450248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Targeting+malignant+B-cell+lymphoma+with+a+humanized+anti-CD22+scFv-angiogenin+immunoenzyme.&rft.au=Krauss%2C+J%C3%BCrgen%3BArndt%2C+Michaela+A+E%3BVu%2C+Bang+K%3BNewton%2C+Dianne+L%3BRybak%2C+Susanna+M&rft.aulast=Krauss&rft.aufirst=J%C3%BCrgen&rft.date=2005-03-01&rft.volume=128&rft.issue=5&rft.spage=602&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 - 2005-04-12 N1 - Date created - 2005-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy'). AN - 67446160; 15496938 AB - 3,4-Methylenedioxymethamphetamine (MDMA, or 'Ecstasy') is an illicit drug that stimulates the release of serotonin (5-HT) and dopamine (DA) from neurons. Recent evidence reveals that drug users are ingesting piperazine analogs, like 1-benzylpiperazine (BZP, or 'A2') and 1-(m-trifluoromethylphenyl)piperazine (TFMPP, or 'Molly'), to mimic psychoactive effects of MDMA. In the present study, we compared the neurochemistry of MDMA, BZP, and TFMPP in rats. The effects of MDMA, BZP, and TFMPP on transporter-mediated efflux of [3H]5-HT and [3H]MPP+ (DA transporter substrate) were determined in synaptosomes. The effects of drugs on extracellular levels of 5-HT and DA were examined using in vivo microdialysis in conscious rats. MDMA evoked transporter-mediated release of [3H]5-HT and [3H]MPP+. BZP released [3H]MPP+, whereas TFMPP was a selective releaser of [3H]5-HT. MDMA (1-3 mg/kg, i.v.) increased dialysate 5-HT and DA in a dose-related fashion, with actions on 5-HT being predominant. BZP (3-10 mg/kg, i.v.) elevated dialysate DA and 5-HT, while TFMPP (3-10 mg/kg, i.v.) elevated 5-HT. Administration of BZP plus TFMPP at a 1:1 ratio (BZP/TFMPP) produced parallel increases in dialysate 5-HT and DA; a 3 mg/kg dose of BZP/TFMPP mirrored the effects of MDMA. At a 10 mg/kg dose, BZP/TFMPP increased dialysate DA more than the summed effects of each drug alone, and some rats developed seizures. Our results show that BZP/TFMPP and MDMA share the ability to evoke monoamine release, but dangerous drug-drug synergism may occur when piperazines are coadministered at high doses. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Baumann, Michael H AU - Clark, Robert D AU - Budzynski, Allison G AU - Partilla, John S AU - Blough, Bruce E AU - Rothman, Richard B AD - Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. mbaumann@intra.nida.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 550 EP - 560 VL - 30 IS - 3 SN - 0893-133X, 0893-133X KW - Piperazines KW - 0 KW - Receptors, Serotonin KW - Serotonin KW - 333DO1RDJY KW - N-Methyl-3,4-methylenedioxyamphetamine KW - KE1SEN21RM KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Index Medicus KW - Receptors, Serotonin -- physiology KW - Animals KW - Synaptosomes -- drug effects KW - Humans KW - Disease Models, Animal KW - Dopamine -- metabolism KW - Receptors, Serotonin -- metabolism KW - Microdialysis KW - Rats KW - Rats, Sprague-Dawley KW - Kinetics KW - Norepinephrine -- metabolism KW - Serotonin -- metabolism KW - Synaptosomes -- metabolism KW - Male KW - Substance-Related Disorders KW - N-Methyl-3,4-methylenedioxyamphetamine -- pharmacology KW - Piperazines -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67446160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=N-substituted+piperazines+abused+by+humans+mimic+the+molecular+mechanism+of+3%2C4-methylenedioxymethamphetamine+%28MDMA%2C+or+%27Ecstasy%27%29.&rft.au=Baumann%2C+Michael+H%3BClark%2C+Robert+D%3BBudzynski%2C+Allison+G%3BPartilla%2C+John+S%3BBlough%2C+Bruce+E%3BRothman%2C+Richard+B&rft.aulast=Baumann&rft.aufirst=Michael&rft.date=2005-03-01&rft.volume=30&rft.issue=3&rft.spage=550&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 - 2005-04-21 N1 - Date created - 2005-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prophylactic high-dose N(omega)-monomethyl-L-arginine prevents the late cardiac dysfunction associated with lethal tumor necrosis factor-alpha challenge in dogs. AN - 67439480; 15718929 AB - We investigated nitric oxide (NO) as a possible cause of the cardiac dysfunction associated with high, lethal doses of tumor necrosis factor-alpha (TNF-alpha) in dogs. Eighty-seven awake, 2-year-old (10-12 kg), purpose-bred beagles were randomized to receive an infusion of saline or N-monomethyl-L-arginine (L-NMMA), a nonselective NO synthase (NOS) inhibitor, as a 40 mg kg bolus followed by a 40 mg kg(-1) h(-1) infusion for 3 to 6 h 3 h before (prophylactic) or 3 h after (therapeutic) challenge with TNF-alpha (60 microg kg(-1)) or vehicle. Serial radionuclide-heart scans and thermodilution pulmonary artery catheter hemodynamic measurements were performed. The effects of prophylactic L-NMMA on TNF-alpha-induced cardiac dysfunction as measured by decreases in mean left ventricular (LV) ejection fraction and downward and rightward shifts of LV function plots (peak systolic pressure versus end systolic volume index and LV stroke work index versus end diastolic volume index) were significantly different comparing early (3-6 h) and delayed (24 h) time points (P = 0.02). Prophylactic L-NMMA therapy did not appear to fully prevent early (3-6 h) TNF-alpha-induced cardiac dysfunction, but at 24 h, complete protection was seen. Therapeutic L-NMMA did not appear to fully protect the heart from TNF-alpha-induced early or delayed cardiac dysfunction (P = NS). Similarly, L-NMMA given prophylactically, but not therapeutically, blocked TNF-alpha-induced increases in exhaled NO flow rates and plasma nitrite and nitrate concentrations (both P = 0.02). These data suggest that TNF-alpha initiates two phases of cardiac injury: an early (3-6 h) phase that may be partially NO independent and a delayed (24 h) phase that is NO dependent. The delayed, more persistent dysfunction can be completely blocked by high doses of a nonselective NOS inhibitor administered before TNF-alpha. JF - Shock (Augusta, Ga.) AU - Sevransky, Jonathan AU - Vandivier, R William AU - Gerstenberger, Eric AU - Correa, Rosalee AU - Ferantz, Victor AU - Banks, Steven M AU - Danner, Robert L AU - Eichacker, Peter Q AU - Natanson, Charles AD - Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland, USA. sevransj@jhmi.edu Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 281 EP - 288 VL - 23 IS - 3 SN - 1073-2322, 1073-2322 KW - Enzyme Inhibitors KW - 0 KW - Nitrates KW - Nitrites KW - Tumor Necrosis Factor-alpha KW - omega-N-Methylarginine KW - 27JT06E6GR KW - Nitric Oxide KW - 31C4KY9ESH KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Index Medicus KW - Ventricular Function, Left -- drug effects KW - Nitrites -- blood KW - Animals KW - Heart Rate -- drug effects KW - Nitric Oxide Synthase -- antagonists & inhibitors KW - Dogs KW - Nitric Oxide -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Vascular Resistance -- drug effects KW - Blood Pressure -- drug effects KW - Stroke Volume -- drug effects KW - Nitrates -- blood KW - omega-N-Methylarginine -- therapeutic use KW - Tumor Necrosis Factor-alpha -- toxicity KW - Heart Diseases -- drug therapy KW - omega-N-Methylarginine -- administration & dosage KW - Heart Diseases -- chemically induced KW - Heart Diseases -- prevention & control KW - Heart Diseases -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67439480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Shock+%28Augusta%2C+Ga.%29&rft.atitle=Prophylactic+high-dose+N%28omega%29-monomethyl-L-arginine+prevents+the+late+cardiac+dysfunction+associated+with+lethal+tumor+necrosis+factor-alpha+challenge+in+dogs.&rft.au=Sevransky%2C+Jonathan%3BVandivier%2C+R+William%3BGerstenberger%2C+Eric%3BCorrea%2C+Rosalee%3BFerantz%2C+Victor%3BBanks%2C+Steven+M%3BDanner%2C+Robert+L%3BEichacker%2C+Peter+Q%3BNatanson%2C+Charles&rft.aulast=Sevransky&rft.aufirst=Jonathan&rft.date=2005-03-01&rft.volume=23&rft.issue=3&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Shock+%28Augusta%2C+Ga.%29&rft.issn=10732322&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-11 N1 - Date created - 2005-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathogen inactivation technology: cleansing the blood supply. AN - 67437424; 15715679 AB - The calculated residual infectious risk of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) from blood transfusion is extremely low. However, the risk of bacterial contamination remains and a variety of other agents including emerging viruses, protozoa and tick-borne agents threaten blood supplies and undermine public confidence in blood safety. Traditional methods of donor screening and testing have limited ability to further reduce disease transmission and cannot prevent an emerging infectious agent from entering the blood supply. Pathogen inactivation technologies have all but eliminated the infectious risks of plasma-derived protein fractions, but as yet no technique has proved sufficiently safe and effective for traditional blood components. Half-way technologies can reduce the risk of pathogen transmission from fresh frozen plasma and cryoprecipitate. Traditional methods of mechanical removal such as washing and filtration have limited success in reducing the risk of cell-associated agents, but methods aimed at sterilizing blood have either proved toxic to the cells or to the recipients of blood components. Several promising methods that target pathogen nucleic acid have recently entered clinical testing. JF - Journal of internal medicine AU - Klein, H G AD - Department of Medicine and Pathology, The Johns Hopkins School of Medicine, Baltimore, MD, USA. hklein@cc.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 224 EP - 237 VL - 257 IS - 3 SN - 0954-6820, 0954-6820 KW - Index Medicus KW - Acquired Immunodeficiency Syndrome -- prevention & control KW - Hepatitis -- blood KW - Blood Platelets -- microbiology KW - Acquired Immunodeficiency Syndrome -- virology KW - Disinfection -- methods KW - Acquired Immunodeficiency Syndrome -- blood KW - Hepatitis -- virology KW - Humans KW - Acquired Immunodeficiency Syndrome -- transmission KW - Hepatitis -- prevention & control KW - Erythrocytes -- microbiology KW - Graft vs Host Disease -- etiology KW - Communicable Disease Control -- methods KW - Blood Transfusion -- adverse effects KW - Blood-Borne Pathogens UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67437424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+internal+medicine&rft.atitle=Pathogen+inactivation+technology%3A+cleansing+the+blood+supply.&rft.au=Klein%2C+H+G&rft.aulast=Klein&rft.aufirst=H&rft.date=2005-03-01&rft.volume=257&rft.issue=3&rft.spage=224&rft.isbn=&rft.btitle=&rft.title=Journal+of+internal+medicine&rft.issn=09546820&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-31 N1 - Date created - 2005-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cannabinoid CB1 receptor antagonists as promising new medications for drug dependence. AN - 67436556; 15525797 AB - This review examines the development of cannabinoid CB(1) receptor antagonists as a new class of therapeutic agents for drug addiction. Abused drugs [alcohol, opiates, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), and psychostimulants, including nicotine] elicit a variety of chronically relapsing disorders by interacting with endogenous neural pathways in the brain. In particular, they share the common property of activating mesolimbic dopamine brain reward systems, and virtually all abused drugs elevate dopamine levels in the nucleus accumbens. Cannabinoid CB(1) receptors are expressed in this brain reward circuit and modulate the dopamine-releasing effects of Delta(9)-THC and nicotine. Rimonabant (SR141716), a CB(1) receptor antagonist, blocks both the dopamine-releasing and discriminative and rewarding effects of Delta(9)-THC in animals. Blockade of CB(1) receptor activity by genetic invalidation also decreases rewarding effects of opiates and alcohol in animals. Although CB(1) receptor blockade is generally ineffective in reducing the self-administration of cocaine in rodents and primates, it reduces the reinstatement of extinguished cocaine-seeking behavior produced by cocaine-associated conditioned stimuli and cocaine-priming injections. Likewise, CB(1) receptor blockade is effective in reducing nicotine-seeking behavior induced by re-exposure to nicotine-associated stimuli. Some of these findings have been recently validated in humans. In clinical trials, Rimonabant blocks the subjective effects of Delta(9)-THC in humans and prevents relapse to smoking in exsmokers. Findings from both clinical and preclinical studies suggest that ligands blocking CB(1) receptors offer a novel approach for patients suffering from drug dependence that may be efficacious across different classes of abused drugs. JF - The Journal of pharmacology and experimental therapeutics AU - Le Foll, Bernard AU - Goldberg, Steven R AD - Preclinical Pharmacology Section, NIDA, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. blefoll@intra.nida.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 875 EP - 883 VL - 312 IS - 3 SN - 0022-3565, 0022-3565 KW - Receptor, Cannabinoid, CB1 KW - 0 KW - Dronabinol KW - 7J8897W37S KW - Index Medicus KW - Models, Animal KW - Animals KW - Self Administration KW - Reward KW - Conditioning (Psychology) KW - Humans KW - Dronabinol -- pharmacology KW - Brain -- drug effects KW - Receptor, Cannabinoid, CB1 -- antagonists & inhibitors KW - Substance-Related Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67436556?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Cannabinoid+CB1+receptor+antagonists+as+promising+new+medications+for+drug+dependence.&rft.au=Le+Foll%2C+Bernard%3BGoldberg%2C+Steven+R&rft.aulast=Le+Foll&rft.aufirst=Bernard&rft.date=2005-03-01&rft.volume=312&rft.issue=3&rft.spage=875&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 - 2005-04-05 N1 - Date created - 2005-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cyp2e1-humanized transgenic mouse: role of cyp2e1 in acetaminophen hepatotoxicity. AN - 67435102; 15576447 AB - The cytochrome P450 (P450) CYP2E1 enzyme metabolizes and activates a wide array of toxicological substrates, including alcohols, the widely used analgesic acetaminophen, acetone, benzene, halothane, and carcinogens such as azoxymethane and dimethylhydrazine. Most studies on the biochemical and pharmacological actions of CYP2E1 are derived from studies with rodents, rabbits, and cultured hepatocytes; therefore, extrapolation of the results to humans can be difficult. Creating "humanized" mice by introducing the human CYP2E1 gene into Cyp2e1-null mice can circumvent this disadvantage. A transgenic mouse line expressing the human CYP2E1 gene was established. Western blot and high-performance liquid chromatography/mass spectrometry analyses revealed human CYP2E1 protein expression and enzymatic activity in the liver of CYP2E1-humanized mice. Treatment of mice with the CYP2E1 inducer acetone demonstrated that human CYP2E1 was inducible in this transgenic model. The response to the CYP2E1 substrate acetaminophen was explored in the CYP2E1-humanized mice. Hepatotoxicity, resulting from the CYP2E1-mediated activation of acetaminophen, was demonstrated in the livers of CYP2E1-humanized mice by elevated serum alanine aminotransferase levels, increased hepatocyte necrosis, and decreased P450 levels. These data establish that in this humanized mouse model, human CYP2E1 is functional and can metabolize and activate different CYP2E1 substrates such as chlorzoxazone, p-nitrophenol, acetaminophen, and acetone. CYP2E1-humanized mice will be of great value for delineating the role of human CYP2E1 in ethanol-induced oxidative stress and alcoholic liver damage. They will also function as an important in vivo tool for predicting drug metabolism and disposition and drug-drug interactions of chemicals that are substrates for human CYP2E1. JF - Drug metabolism and disposition: the biological fate of chemicals AU - Cheung, Connie AU - Yu, Ai-Ming AU - Ward, Jerrold M AU - Krausz, Kristopher W AU - Akiyama, Taro E AU - Feigenbaum, Lionel AU - Gonzalez, Frank J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Building 37, Room 3106, 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 449 EP - 457 VL - 33 IS - 3 SN - 0090-9556, 0090-9556 KW - Analgesics, Non-Narcotic KW - 0 KW - Acetone KW - 1364PS73AF KW - Acetaminophen KW - 362O9ITL9D KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Index Medicus KW - Animals KW - Necrosis KW - Enzyme Induction -- drug effects KW - Microsomes, Liver -- metabolism KW - Humans KW - Mice KW - Mice, Transgenic KW - Male KW - Models, Animal KW - Hepatocytes -- drug effects KW - Cytochrome P-450 CYP2E1 -- biosynthesis KW - Analgesics, Non-Narcotic -- toxicity KW - Hepatocytes -- pathology KW - Cytochrome P-450 CYP2E1 -- genetics KW - Acetaminophen -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67435102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+cyp2e1-humanized+transgenic+mouse%3A+role+of+cyp2e1+in+acetaminophen+hepatotoxicity.&rft.au=Cheung%2C+Connie%3BYu%2C+Ai-Ming%3BWard%2C+Jerrold+M%3BKrausz%2C+Kristopher+W%3BAkiyama%2C+Taro+E%3BFeigenbaum%2C+Lionel%3BGonzalez%2C+Frank+J&rft.aulast=Cheung&rft.aufirst=Connie&rft.date=2005-03-01&rft.volume=33&rft.issue=3&rft.spage=449&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 - 2005-08-25 N1 - Date created - 2005-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rituximab plus infusional cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin lymphoma: pooled results from 3 phase 2 trials. AN - 67432467; 15550484 AB - Evidence suggests that infusional therapy is a more effective means for administering cytotoxic therapy than intravenous bolus therapy for lymphoma and offers greater potential for therapeutic synergy with rituximab, which has a long half-life. We pooled the results of 3 prospective phase 2 trials evaluating rituximab in combination with 96-hour infusion of cyclophosphamide (187.5-200 mg/m2 per day), doxorubicin (12.5 mg/m2 per day), and etoposide (60 mg/m2 per day) (R-CDE) plus granulocyte-colony-stimulating factor (G-CSF) in 74 patients with HIV-associated, B-cell non-Hodgkin lymphoma, of whom 56 (76%) patients received concurrent highly active antiretroviral therapy (HAART). The complete remission (CR) rate was 70% (95% confidence interval [CI], 59%-81%), and the estimated 2-year failure-free survival and overall survival rates were 59% (95% CI, 47%-71%) and 64% (95% CI, 52%-76%), respectively. Ten (14%) patients had opportunistic infections during or within 3 months of the end of R-CDE, and 17 (23%) patients developed nonopportunistic infections after that time. Six (8%) patients died because of infection; 2 (3%) of those infections were bacterial sepsis during R-CDE, and 4 (5%) were opportunistic infections that occurred between 2 and 8 months after the completion of R-CDE. R-CDE produced a 70% CR rate and a 59% 2-year failure-free survival rate in patients with HIV-associated lymphoma. Consistent with other reports, adding rituximab to cytotoxic therapy in this population may increase the risk for life-threatening infection. Further studies evaluating rituximab in combination with infusional chemotherapy are warranted, but caution is advised. JF - Blood AU - Spina, Michele AU - Jaeger, Ulrich AU - Sparano, Joseph A AU - Talamini, Renato AU - Simonelli, Cecilia AU - Michieli, Mariagrazia AU - Rossi, Giuseppe AU - Nigra, Ezio AU - Berretta, Massimiliano AU - Cattaneo, Chiara AU - Rieger, Armin C AU - Vaccher, Emanuela AU - Tirelli, Umberto AD - Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occidentale 12, 33081, Aviano (PN) Italy. Y1 - 2005/03/01/ PY - 2005 DA - 2005 Mar 01 SP - 1891 EP - 1897 VL - 105 IS - 5 SN - 0006-4971, 0006-4971 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Murine-Derived KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Rituximab KW - 4F4X42SYQ6 KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Opportunistic Infections KW - Infusions, Intravenous KW - Humans KW - Aged KW - Doxorubicin -- administration & dosage KW - Infection KW - Lymphoma, B-Cell -- drug therapy KW - Lymphoma, B-Cell -- mortality KW - Etoposide -- administration & dosage KW - Adult KW - Antiretroviral Therapy, Highly Active KW - Middle Aged KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Male KW - Female KW - Survival Analysis KW - Remission Induction KW - Lymphoma, AIDS-Related -- mortality KW - Lymphoma, AIDS-Related -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- toxicity KW - Antibodies, Monoclonal -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67432467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Rituximab+plus+infusional+cyclophosphamide%2C+doxorubicin%2C+and+etoposide+in+HIV-associated+non-Hodgkin+lymphoma%3A+pooled+results+from+3+phase+2+trials.&rft.au=Spina%2C+Michele%3BJaeger%2C+Ulrich%3BSparano%2C+Joseph+A%3BTalamini%2C+Renato%3BSimonelli%2C+Cecilia%3BMichieli%2C+Mariagrazia%3BRossi%2C+Giuseppe%3BNigra%2C+Ezio%3BBerretta%2C+Massimiliano%3BCattaneo%2C+Chiara%3BRieger%2C+Armin+C%3BVaccher%2C+Emanuela%3BTirelli%2C+Umberto&rft.aulast=Spina&rft.aufirst=Michele&rft.date=2005-03-01&rft.volume=105&rft.issue=5&rft.spage=1891&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-24 N1 - Date created - 2005-02-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Blood. 2005 Mar 1;105(5):1842 [15747398] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An overview of lung cancer genomics and proteomics. AN - 67431827; 15713815 AB - Lung cancer is the cause of nearly 170,000 cancer deaths in the United States each year, accounting for nearly 25% of all deaths from cancer. The 5-yr survival rate for lung cancer is < 15% from the time of diagnosis. This is largely due to the late stage of diagnosis and the lack of effective treatments, reflecting the need for a better understanding of the mechanisms that underlie lung carcinogenesis. Unlike the study of a single gene, protein, or pathway, genomic and proteomic technologies enable a systematic overview that provides the potential to improve our understanding of this disease. Ultimately, this could improve the diagnosis, prognosis, and clinical management of patients with lung cancer. Here, we review studies that generated profiles of gene and protein expression in lung cancer specimens and relevant model systems, and make recommendations to facilitate the clinical application of these technologies. JF - American journal of respiratory cell and molecular biology AU - Granville, Courtney A AU - Dennis, Phillip A AD - National Cancer Institute/NIH, Building 8, Room 5101, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA. pdennis@nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 169 EP - 176 VL - 32 IS - 3 SN - 1044-1549, 1044-1549 KW - Proteome KW - 0 KW - Index Medicus KW - Protein Array Analysis KW - Gene Expression Profiling KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Disease Models, Animal KW - Mice KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- classification KW - Lung Neoplasms -- metabolism KW - Genomics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67431827?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=An+overview+of+lung+cancer+genomics+and+proteomics.&rft.au=Granville%2C+Courtney+A%3BDennis%2C+Phillip+A&rft.aulast=Granville&rft.aufirst=Courtney&rft.date=2005-03-01&rft.volume=32&rft.issue=3&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-29 N1 - Date created - 2005-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized, phase II trial of ketoconazole plus alendronate versus ketoconazole alone in patients with androgen independent prostate cancer and bone metastases. AN - 67430883; 15711271 AB - Alendronate (AL), a potent oral bisphosphonate, blocks the secretion of matrix metalloproteinase-2 and the establishment of bone metastases in animal models. Ketoconazole (KT) has demonstrated activity in androgen independent prostate cancer (AIPC). In this study we determined whether KT plus AL produced acceptable disease responses compared with KT alone. As the experimental design, 72 patients with progressive AIPC metastatic to bone were randomized to receive KT (1,200 mg daily) plus hydrocortisone (H) (30 mg daily) with or without AL (40 mg daily). Prostate specific antigen (PSA) consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decrease, time to progression and response duration. The pharmacokinetics of KT and AL were characterized and changes in circulating angiogenic factors were assessed. At a median potential followup of 23.9 months the proportion of patients with a greater than 50% decrease in PSA was similar in the KT/H/AL and KT/H, groups (50% and 47%, respectively). The median duration of response was 8.9 and 6.3 months in the KT/H/AL and KT/H groups, respectively (p = 0.125). Median progression-free survival was not significantly prolonged in the KT/H/AL group (4.6 vs 3.8 months, p = 0.27). There was no significant difference in overall survival between the 2 treatment arms but there was a trend toward improved survival in the KT/H arm (p = 0.074). Toxicity in the 2 groups was mild and there were no clear associations between changes in circulating angiogenic factor levels and clinical outcomes in either treatment arm. There were no statistically significant differences in response rate, progression-free survival or overall survival between KT/H alone and KT/H plus AL treatment in patients with AIPC. The addition of AL to KT/H may increase the response duration with an acceptable safety profile compared with treatment with KT/H alone. However, the addition of AL offers no survival benefit in patients with AIPC. JF - The Journal of urology AU - Figg, William D AU - Liu, Yinong AU - Arlen, Philip AU - Gulley, James AU - Steinberg, Seth M AU - Liewehr, David J AU - Cox, Michael C AU - Zhai, Suoping AU - Cremers, Serge AU - Parr, Allyson AU - Yang, Xiaowei AU - Chen, Clara C AU - Jones, Elizabeth AU - Dahut, William L AD - Center for Cancer Research, National Cancer Institute, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. wdfigg@helix.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 790 EP - 796 VL - 173 IS - 3 SN - 0022-5347, 0022-5347 KW - Ketoconazole KW - R9400W927I KW - Alendronate KW - X1J18R4W8P KW - Abridged Index Medicus KW - Index Medicus KW - Drug Therapy, Combination KW - Humans KW - Aged KW - Middle Aged KW - Male KW - Ketoconazole -- pharmacokinetics KW - Prostatic Neoplasms -- pathology KW - Bone Neoplasms -- blood KW - Ketoconazole -- therapeutic use KW - Prostatic Neoplasms -- blood KW - Bone Neoplasms -- drug therapy KW - Alendronate -- therapeutic use KW - Prostatic Neoplasms -- drug therapy KW - Bone Neoplasms -- secondary KW - Alendronate -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67430883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+urology&rft.atitle=A+randomized%2C+phase+II+trial+of+ketoconazole+plus+alendronate+versus+ketoconazole+alone+in+patients+with+androgen+independent+prostate+cancer+and+bone+metastases.&rft.au=Figg%2C+William+D%3BLiu%2C+Yinong%3BArlen%2C+Philip%3BGulley%2C+James%3BSteinberg%2C+Seth+M%3BLiewehr%2C+David+J%3BCox%2C+Michael+C%3BZhai%2C+Suoping%3BCremers%2C+Serge%3BParr%2C+Allyson%3BYang%2C+Xiaowei%3BChen%2C+Clara+C%3BJones%2C+Elizabeth%3BDahut%2C+William+L&rft.aulast=Figg&rft.aufirst=William&rft.date=2005-03-01&rft.volume=173&rft.issue=3&rft.spage=790&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+urology&rft.issn=00225347&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-29 N1 - Date created - 2005-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coronary heart disease after radiotherapy for peptic ulcer disease. AN - 67430389; 15708264 AB - To evaluate the risk of coronary heart disease (CHD) and cerebrovascular disease after radiotherapy (RT) for peptic ulcer disease. Peptic ulcer disease patients treated with RT (n = 1859) or by other means (n = 1860) at the University of Chicago Medical Center between 1936 and 1965, were followed through 1997. The observed numbers of cause-specific deaths were compared with the expected numbers from the general population rates. During RT, 5% of the heart was in the treatment field and the remainder of the heart mostly received scattered radiation. A volume-weighted cardiac dose was computed to describe the average tissue dose to the entire organ. We used Cox proportional hazards regression analysis to analyze the CHD and cerebrovascular disease risk associated with RT, adjusting for confounding factors. Greater than expected CHD mortality was observed among the irradiated patients. The irradiated patients received volume-weighted cardiac doses ranging from 1.6 to 3.9 Gy and the portion of the heart directly in the field received doses of 7.6-18.4 Gy. The CHD risk increased with the cardiac dose (p trend = 0.01). The cerebrovascular disease risk was not associated with the surrogate carotid dose. The excess CHD risk in patients undergoing RT for peptic ulcer disease decades previously indicates the need for long-term follow-up for cardiovascular disease after chest RT. JF - International journal of radiation oncology, biology, physics AU - Carr, Zhanat A AU - Land, Charles E AU - Kleinerman, Ruth A AU - Weinstock, Robert W AU - Stovall, Marilyn AU - Griem, Melvin L AU - Mabuchi, Kiyohiko AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH/DHHS, 6120 Executive Boulevard, EPS 7038, Rockville, MD 20852, USA. Y1 - 2005/03/01/ PY - 2005 DA - 2005 Mar 01 SP - 842 EP - 850 VL - 61 IS - 3 SN - 0360-3016, 0360-3016 KW - Index Medicus KW - Regression Analysis KW - Risk Factors KW - Radiotherapy Dosage KW - Humans KW - Confounding Factors (Epidemiology) KW - Cohort Studies KW - Adult KW - Smoking -- adverse effects KW - Middle Aged KW - Male KW - Female KW - Cause of Death KW - Peptic Ulcer -- radiotherapy KW - Coronary Disease -- etiology KW - Coronary Disease -- mortality KW - Heart -- radiation effects KW - Stroke -- etiology KW - Stroke -- mortality KW - Radiation Injuries -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67430389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+oncology%2C+biology%2C+physics&rft.atitle=Coronary+heart+disease+after+radiotherapy+for+peptic+ulcer+disease.&rft.au=Carr%2C+Zhanat+A%3BLand%2C+Charles+E%3BKleinerman%2C+Ruth+A%3BWeinstock%2C+Robert+W%3BStovall%2C+Marilyn%3BGriem%2C+Melvin+L%3BMabuchi%2C+Kiyohiko&rft.aulast=Carr&rft.aufirst=Zhanat&rft.date=2005-03-01&rft.volume=61&rft.issue=3&rft.spage=842&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-24 N1 - Date created - 2005-02-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Int J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):957; author reply 957 [16751083] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polychlorinated biphenyls and menstrual cycle characteristics. AN - 67420623; 15703533 AB - Experimental studies in nonhuman primates provide evidence that low-level exposure to persistent organochlorine pollutants such as polychlorinated biphenyls (PCBs) may affect aspects of their menstrual cycle, including cycle length, regularity, and bleeding duration. Few studies have examined these associations in humans. We used data from 2314 pregnant women who participated in the Collaborative Perinatal Project, a cohort study that enrolled pregnant women in the 1960s in 12 centers in the United States. Information about usual (prepregnancy) menstrual cycle length, regularity, bleeding duration, and dysmenorrhea was collected at enrollment, and 11 PCBs and p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) were measured in stored blood samples collected during the third trimester of pregnancy. We used multivariate linear and logistic regression to examine the association between organochlorine levels and menstrual cycles, adjusting for demographic factors, cholesterol, and triglycerides. Total PCBs were positively associated with increasing menstrual cycle length (adjusted difference across 5 categories of PCB exposure = 0.7 days, trend-test P value = 0.02). Irregular cycles were slightly more frequent among those in the 2 highest categories of PCB exposure (odds ratio for highest category = 1.5; 95% confidence interval = 0.70-3.3), and there also was some evidence of an association with DDE. The strengths of these associations increased with various exclusions made to decrease potential misclassification of the outcome and the exposures. There was little evidence for associations between DDE or PCBs and bleeding duration, heavy bleeding, or dysmenorrhea. This study supports experimental studies in monkeys showing an effect of low-dose PCB exposure on menstrual function. JF - Epidemiology (Cambridge, Mass.) AU - Cooper, Glinda S AU - Klebanoff, Mark A AU - Promislow, Joanne AU - Brock, John W AU - Longnecker, Matthew P AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. cooper1@niehs.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 191 EP - 200 VL - 16 IS - 2 SN - 1044-3983, 1044-3983 KW - Environmental Pollutants KW - 0 KW - Insecticides KW - Dichlorodiphenyl Dichloroethylene KW - 4M7FS82U08 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Epidemiologic Studies KW - Humans KW - Cohort Studies KW - Adult KW - Middle Aged KW - Adolescent KW - Female KW - Pregnancy KW - Multivariate Analysis KW - Insecticides -- poisoning KW - Dichlorodiphenyl Dichloroethylene -- poisoning KW - Environmental Pollutants -- poisoning KW - Environmental Exposure KW - Polychlorinated Biphenyls -- poisoning KW - Menstrual Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67420623?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Polychlorinated+biphenyls+and+menstrual+cycle+characteristics.&rft.au=Cooper%2C+Glinda+S%3BKlebanoff%2C+Mark+A%3BPromislow%2C+Joanne%3BBrock%2C+John+W%3BLongnecker%2C+Matthew+P&rft.aulast=Cooper&rft.aufirst=Glinda&rft.date=2005-03-01&rft.volume=16&rft.issue=2&rft.spage=191&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 - 2005-05-10 N1 - Date created - 2005-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the DEAD-box RNA helicase eIF4AII characterizes its interaction with transformation suppressor Pdcd4 and eIF4GI. AN - 67415976; 15661843 AB - Eukaryotic initiation factor (eIF) 4A unwinds secondary and tertiary structures in the 5'-untranslated region of mRNA, permitting translation initiation. Programmed cell death 4 (Pdcd4) is a novel transformation suppressor and eIF4A-binding partner that inhibits eIF4A helicase activity and translation. To elucidate the regions of eIF4A that are functionally significant in binding to Pdcd4, we generated point mutations of eIF4A. Two-hybrid analysis revealed that five eIF4A mutants completely lost binding to Pdcd4 while four eIF4A mutants retained wild-type levels of binding. The residues that, when mutated, inactivated Pdcd4 binding specified ATP binding, ATP hydrolysis, or RNA binding. With the exception of the Q-motif mutant eIF4AP56L, the eIF4A mutants inactivated for Pdcd4 binding were inactivated for binding to eIF4G (GM, GC, or both) and for enhancing translation. Several eIF4A mutants showing wild-type level binding to Pdcd4 were also inactivated for binding to eIF4G and for enhancing translation. Thus, significant dissociation of eIF4A's Pdcd4- and eIF4G-binding regions appears to occur. Because three of the four eIF4A mutants that retained Pdcd4 binding also suppressed translation activity in a dominant-negative manner, the structure that defines the Pdcd4-binding domain of eIF4A may be necessary but is insufficient for translation. A structural homology model of eIF4A shows regions important for binding to Pdcd4 and/or eIF4G lying on the perimeters of the hinge area of eIF4A. A competition experiment revealed that Pdcd4 competes with C-terminal eIF4G for binding to eIF4A. In summary, the Pdcd4-binding domains on eIF4A impact both binding to eIF4G and translation initiation in cells. JF - RNA (New York, N.Y.) AU - Zakowicz, Halina AU - Yang, Hsin-Sheng AU - Stark, Cristi AU - Wlodawer, Alexander AU - Laronde-Leblanc, Nicole AU - Colburn, Nancy H AD - Laboratory of Cancer Prevention, Bldg. 576, Rm. 101, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 261 EP - 274 VL - 11 IS - 3 SN - 1355-8382, 1355-8382 KW - DNA Primers KW - 0 KW - EIF4G1 protein, human KW - Eukaryotic Initiation Factor-4G KW - Peptide Fragments KW - Peptide Initiation Factors KW - Eukaryotic Initiation Factor-4A KW - EC 2.7.7.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Protein Biosynthesis KW - Base Sequence KW - Models, Molecular KW - Point Mutation KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Binding KW - Peptide Fragments -- metabolism KW - Peptide Initiation Factors -- metabolism KW - Eukaryotic Initiation Factor-4A -- metabolism KW - Eukaryotic Initiation Factor-4A -- genetics KW - Eukaryotic Initiation Factor-4A -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67415976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=RNA+%28New+York%2C+N.Y.%29&rft.atitle=Mutational+analysis+of+the+DEAD-box+RNA+helicase+eIF4AII+characterizes+its+interaction+with+transformation+suppressor+Pdcd4+and+eIF4GI.&rft.au=Zakowicz%2C+Halina%3BYang%2C+Hsin-Sheng%3BStark%2C+Cristi%3BWlodawer%2C+Alexander%3BLaronde-Leblanc%2C+Nicole%3BColburn%2C+Nancy+H&rft.aulast=Zakowicz&rft.aufirst=Halina&rft.date=2005-03-01&rft.volume=11&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=RNA+%28New+York%2C+N.Y.%29&rft.issn=13558382&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-21 N1 - Date created - 2005-02-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1999 Apr 30;274(18):12236-44 [10212190] RNA. 1998 Jul;4(7):828-36 [9671055] Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14037-42 [10570194] Mol Cell Biol. 2000 Jan;20(2):468-77 [10611225] Mol Cell Biol. 2000 Aug;20(16):6019-29 [10913184] J Biol Chem. 2000 Aug 11;275(32):24776-80 [10811643] Genome Res. 2000 Aug;10(8):1172-84 [10958635] Trends Biochem Sci. 2000 Sep;25(9):423-6 [10973054] Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13080-5 [11087862] J Biol Chem. 2000 Dec 29;275(52):41369-76 [11022043] Oncogene. 2001 Feb 8;20(6):669-76 [11314000] RNA. 2001 Mar;7(3):382-94 [11333019] J Biol Chem. 2001 Jan 26;276(4):2872-9 [11060291] J Biol Chem. 2001 Aug 3;276(31):29111-5 [11408474] J Biol Chem. 2001 Aug 17;276(33):30914-22 [11418588] Mol Cell. 2001 Aug;8(2):251-62 [11545728] Mol Cell Biol. 2003 Jan;23(1):26-37 [12482958] Mol Cell. 2003 Jan;11(1):127-38 [12535527] Oncogene. 2003 Jun 12;22(24):3712-20 [12802278] Biol Cell. 2003 May-Jun;95(3-4):157-67 [12867080] Nat Rev Mol Cell Biol. 2004 Mar;5(3):232-41 [14991003] Mol Cell Biol. 2004 May;24(9):3894-906 [15082783] Oncogene. 2004 Oct 21;23(49):8135-45 [15361828] J Biol Chem. 1985 Jun 25;260(12):7651-8 [3838990] Nature. 1989 Jan 12;337(6203):121-2 [2563148] Mol Cell Biol. 1990 Mar;10(3):1134-44 [2304461] EMBO J. 1992 Jul;11(7):2643-54 [1378397] Mol Cell Biol. 1993 Nov;13(11):6789-98 [8413273] EMBO J. 1994 Mar 1;13(5):1205-15 [8131750] Eur J Biochem. 1996 Mar 15;236(3):747-71 [8665893] Mol Cell Biol. 1997 Dec;17(12):6940-7 [9372926] Mol Cell Biol. 1997 Dec;17(12):7283-94 [9372960] Electrophoresis. 1997 Dec;18(15):2714-23 [9504803] Am J Physiol Cell Physiol. 2004 Dec;287(6):C1541-6 [15317660] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis, structure-activity relationship, and p210(bcr-abl) protein tyrosine kinase activity of novel AG 957 analogs. AN - 67413833; 15698792 AB - A series of novel, sterically hindered lipophilic analogs of AG 957 was designed and synthesized as potential protein tyrosine kinase (PTK) inhibitors. The in vitro activity, in vivo anti-leukemia activity, and pharmacology of these PTK inhibitors were studied. Some aspects of the structure-activity relationship associated with the carboxylic acid, phenol ring, and linker modifications are discussed. We have demonstrated that the 1,4-hydroquinone moiety is essential for activity and that sterically hindered esters contribute to enhanced in vivo efficacy. Adaphostin (NSC 680410) has emerged as the improved compound with the maximum in vivo anti-leukemia hollow fiber activity, concordant with the original lead compound AG 957. Currently, adaphostin is undergoing preclinical toxicology studies. JF - Bioorganic & medicinal chemistry AU - Kaur, Gurmeet AU - Narayanan, Ven L AU - Risbood, Prabhakar A AU - Hollingshead, Melinda G AU - Stinson, Sherman F AU - Varma, Ravi K AU - Sausville, Edward A AD - Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2005/03/01/ PY - 2005 DA - 2005 Mar 01 SP - 1749 EP - 1761 VL - 13 IS - 5 SN - 0968-0896, 0968-0896 KW - Enzyme Inhibitors KW - 0 KW - Tyrphostins KW - tyrphostin AG957 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Fusion Proteins, bcr-abl KW - EC 2.7.10.2 KW - Index Medicus KW - Structure-Activity Relationship KW - Tyrphostins -- pharmacokinetics KW - Tyrphostins -- chemistry KW - Enzyme Inhibitors -- chemistry KW - Enzyme Inhibitors -- pharmacology KW - Enzyme Inhibitors -- pharmacokinetics KW - Enzyme Inhibitors -- chemical synthesis KW - Protein-Tyrosine Kinases -- metabolism KW - Tyrphostins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67413833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry&rft.atitle=Synthesis%2C+structure-activity+relationship%2C+and+p210%28bcr-abl%29+protein+tyrosine+kinase+activity+of+novel+AG+957+analogs.&rft.au=Kaur%2C+Gurmeet%3BNarayanan%2C+Ven+L%3BRisbood%2C+Prabhakar+A%3BHollingshead%2C+Melinda+G%3BStinson%2C+Sherman+F%3BVarma%2C+Ravi+K%3BSausville%2C+Edward+A&rft.aulast=Kaur&rft.aufirst=Gurmeet&rft.date=2005-03-01&rft.volume=13&rft.issue=5&rft.spage=1749&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 - 2005-07-25 N1 - Date created - 2005-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Continuous dopaminergic stimulation reduces risk of motor complications in parkinsonian primates. AN - 67410613; 15698620 AB - Levodopa or short-acting dopamine (DA) agonist treatment of advanced parkinsonian patients exposes striatal DA receptors to non-physiologic intermittent stimulation that contributes to the development of dyskinesias and other motor complications. To determine whether continuous dopaminergic stimulation can delay or prevent onset of motor complications, four MPTP-lesioned, levodopa-naive cynomolgus monkeys were implanted subcutaneously with apomorphine containing ethylene vinyl acetate rods. Three other MPTP-lesioned monkeys received daily injections of apomorphine. Animals receiving apomorphine rods showed improved motor function ('ON' state) within 1 day of implantation, and remained continually 'ON' for the duration of treatment (up to 6 months) without developing dyskinesias. Injected animals also showed similar improvement in motor function after each apomorphine injection. However, these primates remained 'ON' for only 90 min and within 7-10 days all developed severe dyskinesias. Implanted monkeys evidenced local irritation, which was alleviated by steroid co-therapy. JF - Experimental neurology AU - Bibbiani, Francesco AU - Costantini, Lauren C AU - Patel, Raj AU - Chase, Thomas N AD - Experimental Therapeutic Branch, Building 10, Room 5C103, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1406, USA. Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 73 EP - 78 VL - 192 IS - 1 SN - 0014-4886, 0014-4886 KW - Antiparkinson Agents KW - 0 KW - Dopamine Agonists KW - Drug Implants KW - Polyvinyls KW - Steroids KW - ethylenevinylacetate copolymer KW - 24937-78-8 KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Steroids -- therapeutic use KW - Animals KW - Polyvinyls -- administration & dosage KW - Drug Administration Schedule KW - Macaca fascicularis KW - Dose-Response Relationship, Drug KW - Polyvinyls -- adverse effects KW - Inflammation -- chemically induced KW - Disease Models, Animal KW - Inflammation -- drug therapy KW - Recovery of Function -- drug effects KW - Injections, Subcutaneous KW - Male KW - Movement -- drug effects KW - Apomorphine -- administration & dosage KW - Antiparkinson Agents -- adverse effects KW - Apomorphine -- adverse effects KW - Parkinsonian Disorders -- physiopathology KW - Antiparkinson Agents -- administration & dosage KW - Dyskinesias -- etiology KW - Apomorphine -- blood KW - Dyskinesias -- prevention & control KW - Dopamine Agonists -- adverse effects KW - Dopamine Agonists -- administration & dosage KW - Parkinsonian Disorders -- drug therapy KW - Parkinsonian Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67410613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Continuous+dopaminergic+stimulation+reduces+risk+of+motor+complications+in+parkinsonian+primates.&rft.au=Bibbiani%2C+Francesco%3BCostantini%2C+Lauren+C%3BPatel%2C+Raj%3BChase%2C+Thomas+N&rft.aulast=Bibbiani&rft.aufirst=Francesco&rft.date=2005-03-01&rft.volume=192&rft.issue=1&rft.spage=73&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 - 2005-04-14 N1 - Date created - 2005-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Airpuff startle probes: an efficacious and less aversive alternative to white-noise. AN - 67349620; 15620795 AB - Fear-potentiated startle (FPS) is an increasingly popular psychophysiological method for the objective assessment of fear and anxiety. Studies applying this method often elicit the startle reflex with loud white-noise stimuli. Such intense stimuli may, however, alter psychological processes of interest by creating unintended emotional or attentional artifacts. Additionally, loud acoustic probes may be unsuitable for use with infants, children, the elderly, and those with hearing damage. Past studies have noted robust and reliable startle reflexes elicited by low intensity airpuffs. The current study compares the aversiveness of white-noise (102 dB) and airpuff (3 psi) probes and examines the sensitivity of each probe for the assessment of fear-potentiated startle. Results point to less physiological arousal and self-reported reactivity to airpuff versus white-noise probes. Additionally, both probes elicited equal startle magnitudes, response probabilities, and levels of fear-potentiated startle. Such results support the use of low intensity airpuffs as efficacious and relatively non-aversive startle probes. JF - Biological psychology AU - Lissek, Shmuel AU - Baas, Johanna M P AU - Pine, Daniel S AU - Orme, Kaebah AU - Dvir, Sharone AU - Nugent, Monique AU - Rosenberger, Emily AU - Rawson, Elizabeth AU - Grillon, Christian AD - Mood and Anxiety Disorders Program, National Institute of Mental Health (NIH), DHHS, 15K North Drive, Bldg 15k, MSC 2670, Bethesda, MD 20892-2670, USA. lisseks@intra.nimh.nih.gov Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 283 EP - 297 VL - 68 IS - 3 SN - 0301-0511, 0301-0511 KW - Index Medicus KW - Emotions KW - Artifacts KW - Reproducibility of Results KW - Anxiety Disorders KW - Acoustics KW - Humans KW - Adult KW - Air Movements KW - Male KW - Female KW - Fear KW - Reflex, Startle -- physiology KW - Noise -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67349620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+psychology&rft.atitle=Airpuff+startle+probes%3A+an+efficacious+and+less+aversive+alternative+to+white-noise.&rft.au=Lissek%2C+Shmuel%3BBaas%2C+Johanna+M+P%3BPine%2C+Daniel+S%3BOrme%2C+Kaebah%3BDvir%2C+Sharone%3BNugent%2C+Monique%3BRosenberger%2C+Emily%3BRawson%2C+Elizabeth%3BGrillon%2C+Christian&rft.aulast=Lissek&rft.aufirst=Shmuel&rft.date=2005-03-01&rft.volume=68&rft.issue=3&rft.spage=283&rft.isbn=&rft.btitle=&rft.title=Biological+psychology&rft.issn=03010511&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-10 N1 - Date created - 2004-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathways to reading: the role of oral language in the transition to reading AN - 57193093; 364159 AB - What is the role of oral language in reading competence during the transition to school? Is oral language in preschool best conceptualized as vocabulary knowledge or as more comprehensive language including grammar, vocabulary, and semantics? These questions were examined longitudinally using 1,137 children from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. Children were followed from age 3 through 3rd grade, and the results suggest that oral language conceptualized broadly plays both a direct and an indirect role in word recognition during the transition to school and serves as a better foundation for early reading skill than does vocabulary alone. Implications of these findings are discussed in terms of both theoretical models of early reading and practical implications for policy and assessment. (Original abstract) JF - Developmental Psychology AU - Anonymous AU - NICHD Early Child Care Research Network AD - NICHD Early Child Care Research Network Y1 - 2005/03// PY - 2005 DA - March 2005 SP - 428 EP - 442 VL - 41 IS - 2 SN - 0012-1649, 0012-1649 KW - Longitudinal studies KW - USA KW - Reading KW - Young children KW - Word recognition KW - Vocabulary KW - Spoken language KW - Development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57193093?accountid=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=Pathways+to+reading%3A+the+role+of+oral+language+in+the+transition+to+reading&rft.au=Anonymous%3BNICHD+Early+Child+Care+Research+Network&rft.aulast=Anonymous&rft.aufirst=&rft.date=2005-03-01&rft.volume=41&rft.issue=2&rft.spage=428&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 - 2005-08-05 N1 - Document feature - il. refs. tbls. N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Young children; Reading; Word recognition; Development; Spoken language; Vocabulary; Longitudinal studies; USA ER - TY - JOUR T1 - Human brain derived cell culture models of HIV-1 infection AN - 20696161; 10263163 AB - During the clinical course of acquired immune deficiency syndrome, infection of the CNS by human immunodeficiency virus-1 (HIV-1) may ultimately result in the impairment of cognitive, behavioral and motor functions. Viral neuropathogenesis involves inflammatory molecules and neurotoxins produced from infected and immune-activated lymphocytes, microglial cells and astrocytes. Here, we discuss the current understanding of HIV-1 infection of the CNS and various cell culture systems from the developing human brain in order to study the neurobiology of HIV-1 infection, the mechanisms contributing to HIV-1 infection, and disease progression. JF - Neurotoxicity Research AU - Seth, Pankaj AU - Major, Eugene O AD - Molecular and Cellular Neuroscience, National Brain Research Centre, Manesar, India, major@ninds.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 83 EP - 89 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 8 IS - 1-2 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Central nervous system KW - Acquired immune deficiency syndrome KW - Astrocytes KW - Neuropathogenesis KW - Immunodeficiency KW - Brain KW - Cell culture KW - Lymphocytes KW - Infection KW - Inflammation KW - Nervous system KW - Cognitive ability KW - Human immunodeficiency virus 1 KW - Neurotoxicity KW - Neurotoxins KW - Microglial cells KW - V 22360:AIDS and HIV KW - N3 11028:Neuropharmacology & toxicology KW - W 30945:Fermentation & Cell Culture KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20696161?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicity+Research&rft.atitle=Human+brain+derived+cell+culture+models+of+HIV-1+infection&rft.au=Seth%2C+Pankaj%3BMajor%2C+Eugene+O&rft.aulast=Seth&rft.aufirst=Pankaj&rft.date=2005-03-01&rft.volume=8&rft.issue=1-2&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1007%2FBF03033821 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Central nervous system; Acquired immune deficiency syndrome; Astrocytes; Brain; Immunodeficiency; Neuropathogenesis; Cell culture; Lymphocytes; Infection; Inflammation; Nervous system; Cognitive ability; Neurotoxicity; Neurotoxins; Microglial cells; Human immunodeficiency virus 1 DO - http://dx.doi.org/10.1007/BF03033821 ER - TY - JOUR T1 - Detection of circulating endothelial cells and endothelial progenitor cells by flow cytometry AN - 20642663; 7760291 AB - The finding of angiogenic and vasculogenic cells in the peripheral circulation may have profound effects on the course of a variety of diseases ranging from cancer to cardiovascular disease. These cells are ascribed to be endothelial in nature and are generally referred to as circulating endothelial cells if mature or as endothelial progenitor cells if immature. Different approaches have been used to detect these cells, including in vitro culture, magnetic bead isolation, and flow cytometry. We review flow cytometric methods for the detection and enumeration of these cells and provide technical suggestions to promote the accurate enumeration of circulating endothelial cells and endothelial progenitor cells. JF - Cytometry Part B AU - Khan, Sameena S AU - Solomon, Michael A AU - McCoy Jr, J Philip AD - Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, mccoyj@nhlbi.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 1 EP - 8 PB - John Wiley & Sons, Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 64B IS - 1 SN - 1552-4949, 1552-4949 KW - Biotechnology Research Abstracts (through 1992) KW - Endothelial cells KW - Flow cytometry KW - Stem cells KW - Reviews KW - Angiogenesis KW - Cell culture KW - Cardiovascular diseases KW - Cancer KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20642663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytometry+Part+B&rft.atitle=Detection+of+circulating+endothelial+cells+and+endothelial+progenitor+cells+by+flow+cytometry&rft.au=Khan%2C+Sameena+S%3BSolomon%2C+Michael+A%3BMcCoy+Jr%2C+J+Philip&rft.aulast=Khan&rft.aufirst=Sameena&rft.date=2005-03-01&rft.volume=64B&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cytometry+Part+B&rft.issn=15524949&rft_id=info:doi/10.1002%2Fcyto.b.20040 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Flow cytometry; Endothelial cells; Stem cells; Cell culture; Reviews; Angiogenesis; Cancer; Cardiovascular diseases DO - http://dx.doi.org/10.1002/cyto.b.20040 ER - TY - JOUR T1 - Biomarkers of Oxidative Stress Study II: Are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? AN - 20614675; 7983811 AB - Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg ip) effects of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguanosine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GC-MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG in urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects. JF - Free Radical Biology and Medicine AU - Kadiiska, M B AU - Gladen, B C AU - Baird, D D AU - Germolec, D AU - Graham, L B AU - Parker, C E AU - Nyska, A AU - Wachsman, J T AU - Ames, B N AU - Basu, S AU - Brot, N AU - Fitzgerald, G A AU - Floyd, R A AU - George, M AU - Heinecke, J W AU - Hatch, G E AU - Hensley, K AU - Lawson, J A AU - Marnett, L J AU - Morrow, J D AU - Murray, D M AU - Plastaras, J AU - Roberts II, L J AU - Rokach, J AU - Shigenaga, M K AU - Sohal, R S AU - Sun, J AU - Tice, R R AU - Van Thiel, D H AU - Wellner, D AU - Walter, P B AU - Tomer, K B AU - Mason, R P AU - Barrett, J C AD - Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, MD F0-02, Research Triangle Park, NC 27709, USA, Kadiiska@niehs.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 698 EP - 710 PB - Elsevier Science, The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 38 IS - 6 SN - 0891-5849, 0891-5849 KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - CCl4 KW - Rat KW - Plasma KW - Urine KW - Lipid hydroperoxides KW - TBARS KW - MDA KW - Isoprostanes KW - Protein carbonyls KW - Methionine sulfoxidation KW - Tyrosine products KW - 8-OHdG KW - M1G KW - DNA strand breaks KW - Free radicals KW - Lipids KW - Adducts KW - Leukocytes KW - Poisoning KW - Tyrosine KW - biomarkers KW - Lipid peroxidation KW - Methionine KW - Blood KW - Oxidative stress KW - sulfoxidation KW - DNA KW - Immunoassays KW - carbonyls KW - Malondialdehyde KW - N 14845:Miscellaneous KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20614675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+Radical+Biology+and+Medicine&rft.atitle=Biomarkers+of+Oxidative+Stress+Study+II%3A+Are+oxidation+products+of+lipids%2C+proteins%2C+and+DNA+markers+of+CCl4+poisoning%3F&rft.au=Kadiiska%2C+M+B%3BGladen%2C+B+C%3BBaird%2C+D+D%3BGermolec%2C+D%3BGraham%2C+L+B%3BParker%2C+C+E%3BNyska%2C+A%3BWachsman%2C+J+T%3BAmes%2C+B+N%3BBasu%2C+S%3BBrot%2C+N%3BFitzgerald%2C+G+A%3BFloyd%2C+R+A%3BGeorge%2C+M%3BHeinecke%2C+J+W%3BHatch%2C+G+E%3BHensley%2C+K%3BLawson%2C+J+A%3BMarnett%2C+L+J%3BMorrow%2C+J+D%3BMurray%2C+D+M%3BPlastaras%2C+J%3BRoberts+II%2C+L+J%3BRokach%2C+J%3BShigenaga%2C+M+K%3BSohal%2C+R+S%3BSun%2C+J%3BTice%2C+R+R%3BVan+Thiel%2C+D+H%3BWellner%2C+D%3BWalter%2C+P+B%3BTomer%2C+K+B%3BMason%2C+R+P%3BBarrett%2C+J+C&rft.aulast=Kadiiska&rft.aufirst=M&rft.date=2005-03-01&rft.volume=38&rft.issue=6&rft.spage=698&rft.isbn=&rft.btitle=&rft.title=Free+Radical+Biology+and+Medicine&rft.issn=08915849&rft_id=info:doi/10.1016%2Fj.freeradbiomed.2004.09.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-03-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Adducts; Lipids; Leukocytes; Poisoning; Tyrosine; biomarkers; Methionine; Lipid peroxidation; Blood; Oxidative stress; Isoprostanes; Urine; sulfoxidation; DNA; carbonyls; Immunoassays; Malondialdehyde DO - http://dx.doi.org/10.1016/j.freeradbiomed.2004.09.017 ER - TY - JOUR T1 - Inverse treatment planning based on MRI for HDR prostate brachytherapy AN - 20541571; 8067293 AB - Purpose To develop and optimize a technique for inverse treatment planning based solely on magnetic resonance imaging (MRI) during high-dose-rate brachytherapy for prostate cancer. Methods and materials Phantom studies were performed to verify the spatial integrity of treatment planning based on MRI. Data were evaluated from 10 patients with clinically localized prostate cancer who had undergone two high-dose-rate prostate brachytherapy boosts under MRI guidance before and after pelvic radiotherapy. Treatment planning MRI scans were systematically evaluated to derive a class solution for inverse planning constraints that would reproducibly result in acceptable target and normal tissue dosimetry. Results We verified the spatial integrity of MRI for treatment planning. MRI anatomic evaluation revealed no significant displacement of the prostate in the left lateral decubitus position, a mean distance of 14.47 mm from the prostatic apex to the penile bulb, and clear demarcation of the neurovascular bundles on postcontrast imaging. Derivation of a class solution for inverse planning constraints resulted in a mean target volume receiving 100% of the prescribed dose of 95.69%, while maintaining a rectal volume receiving 75% of the prescribed dose of <5% (mean 1.36%) and urethral volume receiving 125% of the prescribed dose of <2% (mean 0.54%). Conclusion Systematic evaluation of image spatial integrity, delineation uncertainty, and inverse planning constraints in our procedure reduced uncertainty in planning and treatment. JF - International Journal of Radiation Oncology, Biology, & Physics AU - Citrin, Deborah AU - Ning, Holly AU - Guion, Peter AU - Li, Guang AU - Susil, Robert C AU - Miller, Robert W AU - Lessard, Etienne AU - Pouliot, Jean AU - Huchen, Xie AU - Capala, Jacek AU - Coleman, C Norman AU - Camphausen, Kevin AU - Menard, Cynthia AD - Radiation Oncology Branch, CCR, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, citrind@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 1267 EP - 1275 PB - Elsevier Science, Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 61 IS - 4 SN - 0360-3016, 0360-3016 KW - Biotechnology and Bioengineering Abstracts KW - Brachytherapy KW - High dose rate KW - Inverse planning KW - MRI KW - Prostate KW - Pelvis KW - Prostate cancer KW - Rectum KW - Magnetic resonance imaging KW - Dosimetry KW - Radiotherapy KW - Penis KW - Bulbs KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20541571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.atitle=Inverse+treatment+planning+based+on+MRI+for+HDR+prostate+brachytherapy&rft.au=Citrin%2C+Deborah%3BNing%2C+Holly%3BGuion%2C+Peter%3BLi%2C+Guang%3BSusil%2C+Robert+C%3BMiller%2C+Robert+W%3BLessard%2C+Etienne%3BPouliot%2C+Jean%3BHuchen%2C+Xie%3BCapala%2C+Jacek%3BColeman%2C+C+Norman%3BCamphausen%2C+Kevin%3BMenard%2C+Cynthia&rft.aulast=Citrin&rft.aufirst=Deborah&rft.date=2005-03-01&rft.volume=61&rft.issue=4&rft.spage=1267&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.issn=03603016&rft_id=info:doi/10.1016%2Fj.ijrobp.2004.11.024 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-04-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Pelvis; Rectum; Prostate cancer; Brachytherapy; Dosimetry; Magnetic resonance imaging; Radiotherapy; Penis; Bulbs DO - http://dx.doi.org/10.1016/j.ijrobp.2004.11.024 ER - TY - JOUR T1 - Diagnostic and Prognostic Value of Early MR Imaging Vessel Signs in Hyperacute Stroke Patients Imaged <3 Hours and Treated with Recombinant Tissue Plasminogen Activator AN - 20235142; 6187178 AB - BACKGROUND: AND PURPOSE: Analogous to the CT hyperattenuated vessel sign (HMCAS), MR imaging may show hypo-or hyperintense vessels in acute ischemic stroke (AIS) patients. We assessed the diagnostic and prognostic strength of early MR imaging vessel signs in AIS patients treated with intravenous thrombolysis (IVT) within 3 hours of the onset of symptoms. METHODS: We studied AIS patients both treated with IVT and stroke MR imaged within 3 hours of the onset of symptoms and at 2 hours and 24 hours after treatment. We assessed the presence or absence of early vessel signs (hyperintense fluid-attenuated inversion recovery sign [FLAIR HVS]; gradient-echo susceptibility vessel sign [GRE SVS]) compared with a combined MR angiography/perfusion-weighted imaging reference and their strength for predicting clinical outcome (favorable vs. poor, independent vs. dependent, or dead, death), recanalization (by clot composition and flow), and hemorrhage in uni-and multivariate analysis. RESULTS: Fifty-six patients (age range, 76 years +/-13 years; median National Institutes of Health stroke scale score [NIHSSS], 11) met the inclusion criteria. Forty-four patients (78.6%) had a vessel occlusion at baseline; 22 of them (50%) recanalized. Nineteen patients (33.9%) suffered some form of intracranial hemorrhage (ICH), 24 patients (42.9%) had an independent outcome, 18 patients (32.1%) a favorable outcome, and 14 patients died. Compared with our combined reference for vessel status PWI/MRA, the sensitivities of CT HMCAS, FLAIR HVS, and GRE SVS were 40%, 66%, and 34%, respectively, and improved during the hours that followed. Localization was accurately reflected by FLAIR HVS but not by GRE SVS. Only NIHSSS and age were independent predictors for recanalization and all clinical outcomes in multiple logistic regression analysis. CONCLUSION: Although early vessel signs can be helpful in the diagnosis of intravascular disease, they do not independently predict recanalization, ICH, or any of the three clinical outcomes in a multivariate logistic regression model. Thrombus composition as reflected by signal intensity characteristics on GRE and FLAIR does not predict the therapeutic effect of IVT. JF - American Journal of Neuroradiology AU - Schellinger, Peter D AU - Chalela, Julio A AU - Kang, Dong-Wha AU - Latour, Lawrence L AU - Warach, Steven AD - National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD. Department of Neurology, University of Heidelberg, Heidelberg, Germany Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 618 EP - 624 PB - American Society of Neuroradiology, 2210 Midwest Rd. Ste. 207 Oak Brood IL 60521 USA, [mailto:ajnr@interaccess.com] VL - 26 IS - 3 SN - 0195-6108, 0195-6108 KW - CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - thrombolysis KW - Intravenous administration KW - Age KW - Magnetic resonance imaging KW - Stroke KW - Ischemia KW - Hemorrhage KW - t-Plasminogen activator KW - Models KW - Angiography KW - Inversion KW - Multivariate analysis KW - Occlusion KW - Computed tomography KW - Regression analysis KW - W 30910:Imaging KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20235142?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Neuroradiology&rft.atitle=Diagnostic+and+Prognostic+Value+of+Early+MR+Imaging+Vessel+Signs+in+Hyperacute+Stroke+Patients+Imaged+%26lt%3B3+Hours+and+Treated+with+Recombinant+Tissue+Plasminogen+Activator&rft.au=Schellinger%2C+Peter+D%3BChalela%2C+Julio+A%3BKang%2C+Dong-Wha%3BLatour%2C+Lawrence+L%3BWarach%2C+Steven&rft.aulast=Schellinger&rft.aufirst=Peter&rft.date=2005-03-01&rft.volume=26&rft.issue=3&rft.spage=618&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Neuroradiology&rft.issn=01956108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Age; Intravenous administration; thrombolysis; Stroke; Magnetic resonance imaging; Ischemia; Hemorrhage; t-Plasminogen activator; Models; Angiography; Multivariate analysis; Inversion; Occlusion; Computed tomography; Regression analysis ER - TY - JOUR T1 - Clinical Issues and Research in Respiratory Failure from Severe Acute Respiratory Syndrome AN - 199626630; 15591472 AB - The National Heart, Lung, and Blood Institute, along with the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases, convened a panel to develop recommendations for treatment, prevention, and research for respiratory failure from severe acute respiratory syndrome (SARS) and other newly emerging infections. The clinical and pathological features of acute lung injury (ALI) from SARS appear indistinguishable from ALI from other causes. The mainstay of treatments for ALI remains supportive. Patients with ALI from SARS who require mechanical ventilation should receive a lung protective, low tidal volume strategy. Adjuvant treatments recommended include prevention of venous thromboembolism, stress ulcer prophylaxis, and semirecumbent positioning during ventilation. Based on previous experience in Canada, infection control resources and protocols were recommended. Leadership structure, communication, training, and morale are an essential aspect of SARS management. A multicenter, placebo-controlled trial of corticosteroids for late SARS is justified because of widespread clinical use and uncertainties about relative risks and benefits. Studies of combined pathophysiologic endpoints were recommended, with mortality as a secondary endpoint. The group recommended preparation for studies, including protocols, ethical considerations, Web-based registries, and data entry systems. JF - American Journal of Respiratory and Critical Care Medicine AU - Levy, Mitchell M AU - Baylor, Melisse S AU - Bernard, Gordon R AU - Fowler, Rob AU - et al Y1 - 2005/03/01/ PY - 2005 DA - 2005 Mar 01 SP - 518 EP - 26 CY - New York PB - American Thoracic Society VL - 171 IS - 5 SN - 1073449X KW - Medical Sciences--Respiratory Diseases KW - Adrenal Cortex Hormones KW - Antiviral Agents KW - United States KW - Antiviral Agents -- therapeutic use KW - Pulmonary Medicine -- methods KW - Pneumonia -- prevention & control KW - Pulmonary Medicine -- trends KW - Humans KW - Respiratory Insufficiency -- etiology KW - Infection Control -- organization & administration KW - Lung -- pathology KW - Research -- trends KW - Community-Acquired Infections -- prevention & control KW - Adrenal Cortex Hormones -- therapeutic use KW - Severe Acute Respiratory Syndrome -- complications KW - Canada KW - Infection Control -- methods KW - Respiration, Artificial -- methods KW - Severe Acute Respiratory Syndrome -- pathology KW - Community-Acquired Infections -- complications KW - Pneumonia -- complications KW - Clinical Protocols -- standards KW - Pulmonary Medicine -- standards KW - Infection Control -- standards KW - Severe Acute Respiratory Syndrome -- therapy KW - Respiratory Insufficiency -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/199626630?accountid=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=unknown&rft.jtitle=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.atitle=Clinical+Issues+and+Research+in+Respiratory+Failure+from+Severe+Acute+Respiratory+Syndrome&rft.au=Levy%2C+Mitchell+M%3BBaylor%2C+Melisse+S%3BBernard%2C+Gordon+R%3BFowler%2C+Rob%3Bet+al&rft.aulast=Levy&rft.aufirst=Mitchell&rft.date=2005-03-01&rft.volume=171&rft.issue=5&rft.spage=518&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 Central N1 - Copyright - Copyright American Thoracic Society Mar 1, 2005 N1 - Last updated - 2017-01-07 ER - TY - JOUR T1 - Annotation: PANDAS: a model for human autoimmune disease AN - 19836354; 6800595 AB - Background:Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS) is a recently recognized syndrome in which pre-adolescent children have abrupt onsets of tics and/or obsessive-compulsive symptoms, a recurring and remitting course of illness temporally related to streptococcal infections, and associated neurologic findings including adventitious movements, hyperactivity and emotional lability. Methods:Inspired by observations of similar symptoms in children with Sydenham's chorea, a search was undertaken for clinical and laboratory evidence in support of the new syndrome. Results:Consistent and predictable clinical findings have been described in a large case series. Magnetic resonance imaging has supported the postulated pathobiology of the syndrome with evidence of inflammatory changes in basal ganglia. Antibasal ganglia antibodies have been found in some acute cases, mimicking streptococcal antigen epitopes. Conclusions:While PANDAS remains a controversial diagnostic concept, it has stimulated new research endeavors into the possible links between bacterial pathogens, autoimmune reactions, and neuropsychiatric symptoms. JF - Journal of Child Psychology and Psychiatry and Allied Disciplines AU - Swedo, Susan E AU - Grant, Paul J AD - National Institute of Mental Health, Bethesda, Maryland, USA, paul.grant@nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 227 EP - 234 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 46 IS - 3 SN - 0021-9630, 0021-9630 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts; CSA Neurosciences Abstracts KW - Streptococcus KW - Mimicry KW - Emotions KW - Autoimmune diseases KW - Magnetic resonance imaging KW - Pathogens KW - Children KW - Infection KW - Inflammation KW - Chorea KW - Antibodies KW - Mental disorders KW - Obsessive compulsive disorder KW - Lability KW - Basal ganglia KW - Epitopes KW - Hyperactivity KW - N3 11001:Behavioral and Cognitive Neuroscience KW - J 02400:Human Diseases KW - F 06930:Autoimmunity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19836354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Child+Psychology+and+Psychiatry+and+Allied+Disciplines&rft.atitle=Annotation%3A+PANDAS%3A+a+model+for+human+autoimmune+disease&rft.au=Swedo%2C+Susan+E%3BGrant%2C+Paul+J&rft.aulast=Swedo&rft.aufirst=Susan&rft.date=2005-03-01&rft.volume=46&rft.issue=3&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry+and+Allied+Disciplines&rft.issn=00219630&rft_id=info:doi/10.1111%2Fj.1469-7610.2004.00386.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-03-01 N1 - SuppNotes - Tables, 1. N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Emotions; Mimicry; Magnetic resonance imaging; Autoimmune diseases; Pathogens; Infection; Children; Inflammation; Chorea; Mental disorders; Antibodies; Obsessive compulsive disorder; Lability; Epitopes; Basal ganglia; Hyperactivity; Streptococcus DO - http://dx.doi.org/10.1111/j.1469-7610.2004.00386.x ER - TY - JOUR T1 - Measurement of eight scalar and dipolar couplings for methine-methylene pairs in proteins and nucleic acids AN - 19828028; 6533552 AB - A new 3D, spin-state-selective coherence transfer NMR experiment is described that yields accurate measurements for eight scalar or dipolar couplings within a spin system composed of a methylene adjacent to a methine group. Implementations of the experiment have been optimized for proteins and for nucleic acids. The experiments are demonstrated for C super( beta )-C super( alpha ) moieties of the third IgG-binding domain from Streptococcal Protein G (GB3) and for C[Equation]-C[Equation] groups in a 24-nt RNA oligomer. Chemical shifts of C super( alpha ), C super( beta ) and H super( beta ) (respectively C[Equation], C[Equation] and H[Equation]) are dispersed in the three orthogonal dimensions, and the absence of heteronuclear decoupling leads to distinct and well-resolved E.COSY multiplet patterns. In an isotropic sample, the E.COSY displacements correspond to super(1)J sub(C alpha H alpha ), super(2)J sub(C alpha H beta 2)+ super(2)J sub(C alpha H beta 3), super(2)J sub(C beta H alpha ), super(1)J sub(C beta H beta 2)+ super(1)J sub(C beta H beta 3), super(1)J sub(C beta H beta 2)- super(2)J sub(H beta 2H beta 3), super(1)J sub(C beta H beta 3)- super(2)J sub(H beta 2H beta 3), super(3)J sub(H alpha H beta 2) and super(3)J sub(H alpha H beta 3) for proteins, and super(1)J[Equation], super(2)J[Equation]J[Equation], super(2)J[Equation], super(1)J[Equation]+ super(1)J[Equation], super(1)J[Equation]J[Equation], super(1)J[Equation]J[Equation], super(3)J[Equation] and super(3)J[Equation] in nucleic acids. The experiment, based on relaxation-optimized spectroscopy, yields best results when applied to residues where the methine-methylene group corresponds to a reasonably isolated spin system, as applies for C, F, Y, W, D, N and H residues in proteins, or the C[Equation]-C[Equation] groups in nucleic acids. Splittings can be measured under either isotropic or weakly aligned conditions, yielding valuable structural information both through the super(3)J couplings and the one-, two- and three-bond dipolar interactions. Dipolar couplings for 10 out of 13 sidechains in GB3 are found to be in excellent agreement with its X-ray structure, whereas one residue adopts a different backbone geometry, and two residues are subject to extensive chi sub(1) rotamer averaging. The abundance of dipolar couplings can also yield stereospecific assignments of the non-equivalent methylene protons. For the RNA oligomer, dipolar data yielded stereospecific assignments for six out of the eight C[Equation]H sub(2) groups in the loop region of the oligomer, in all cases confirmed by super(1)J[Equation]J[Equation], and H[Equation] resonating downfield of H[Equation]. JF - Journal of Biomolecular NMR AU - Miclet, Emeric AU - Boisbouvier, Jerome AU - Bax, Ad AD - National Institutes of Health, Bethesda, Maryland, 20892-0520, USA Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 201 EP - 216 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 31 IS - 3 SN - 0925-2738, 0925-2738 KW - Microbiology Abstracts B: Bacteriology; Biotechnology and Bioengineering Abstracts KW - Streptococcus KW - nucleic acids KW - Data processing KW - RNA KW - Protons KW - streptococcal protein G KW - Ionizing radiation KW - Abundance KW - N.M.R. KW - Spectroscopy KW - Splitting KW - W 30910:Imaging KW - J 02330:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19828028?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biomolecular+NMR&rft.atitle=Measurement+of+eight+scalar+and+dipolar+couplings+for+methine-methylene+pairs+in+proteins+and+nucleic+acids&rft.au=Miclet%2C+Emeric%3BBoisbouvier%2C+Jerome%3BBax%2C+Ad&rft.aulast=Miclet&rft.aufirst=Emeric&rft.date=2005-03-01&rft.volume=31&rft.issue=3&rft.spage=201&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+NMR&rft.issn=09252738&rft_id=info:doi/10.1007%2Fs10858-005-0175-z LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Data processing; nucleic acids; RNA; Protons; Ionizing radiation; streptococcal protein G; Abundance; N.M.R.; Spectroscopy; Splitting; Streptococcus DO - http://dx.doi.org/10.1007/s10858-005-0175-z ER - TY - JOUR T1 - Health status and plasma dioxin levels in chloracne cases 20 years after the Seveso, Italy accident AN - 19826253; 6252549 AB - Background: The Seveso, Italy accident of 1976 exposed a large population to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or simply dioxin). The accident resulted, mostly among children, in one of the largest ever-reported outbreaks of chloracne, the typical skin disorder due to halogenated-hydrocarbon compounds. Objectives: Approximately 20 years after the accident, we conducted an epidemiological study in Seveso to investigate (a) the health status of chloracne cases; (b) TCDD-chloracne exposure-response relationship; and (c) factors modifying TCDD toxicity. Methods: From 1993 to 1998, we recruited 101 chloracne cases and 211 controls. Trained interviewers administered a structured questionnaire assessing, among other epidemiological variables, information on an extensive list of diseases. During the interview, individual pigmentary characteristics were determined. We measured plasma TCDD levels using high-resolution gas chromatography-mass spectrometry. Results: Plasma TCDD was still elevated (> 10 ppt) in 78 (26.6%) of the 293 subjects with adequate plasma samples, particularly in females, in subjects who had eaten home-grown animals, and in individuals with older age, higher body mass index and residence near the accident site. After 20 years, health conditions of chloracne cases were similar to those of controls from the Seveso area. Elevated plasma TCDD was associated with chloracne [odds ratio (OR) = 3.7, 95% confidence interval (CI) 1.6-8.8, adjusted for age, sex and residence]. Chloracne risk was higher in subjects younger than 8 years at the accident (OR = 7.4, 95% CI 1.8-30.3) and, contrary to previous hypotheses, did not increase at puberty onset or in teenage years. Subjects with elevated TCDD levels and light hair colour had higher relative odds of chloracne (OR = 9.2, 95% CI 2.6-32.5). Conclusions: Dioxin toxicity in chloracne cases was confined to the acute dermatotoxic effects. Chloracne occurrence appeared related to younger age and light hair colour. Age-related dioxin elimination or dilution must be taken into account in interpreting these results. JF - British Journal of Dermatology AU - Baccarelli, A AU - Pesatori, A C AU - Consonni, D AU - Mocarelli, P AU - Patterson, D G AU - Caporaso, N E AU - Bertazzi, P A AU - Landi, M T AD - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, DHHS, 6120 Executive Blvd, EPS 7114, Bethesda, MD 20892-7236, U.S.A, landim@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 459 EP - 465 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 152 IS - 3 SN - 0007-0963, 0007-0963 KW - Toxicology Abstracts KW - Chloracne KW - Inventories KW - Age KW - Skin KW - TCDD KW - Toxicity KW - Children KW - Hair KW - Mass spectroscopy KW - Light effects KW - Accidents KW - Gas chromatography KW - Dose-response effects KW - Risk factors KW - Geriatrics KW - Body mass index KW - Dioxin KW - Puberty KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19826253?accountid=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=British+Journal+of+Dermatology&rft.atitle=Health+status+and+plasma+dioxin+levels+in+chloracne+cases+20+years+after+the+Seveso%2C+Italy+accident&rft.au=Baccarelli%2C+A%3BPesatori%2C+A+C%3BConsonni%2C+D%3BMocarelli%2C+P%3BPatterson%2C+D+G%3BCaporaso%2C+N+E%3BBertazzi%2C+P+A%3BLandi%2C+M+T&rft.aulast=Baccarelli&rft.aufirst=A&rft.date=2005-03-01&rft.volume=152&rft.issue=3&rft.spage=459&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Dermatology&rft.issn=00070963&rft_id=info:doi/10.1111%2Fj.1365-2133.2005.06444.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - SuppNotes - Tables, 3; references, 34. N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Inventories; Chloracne; Age; Skin; TCDD; Toxicity; Children; Hair; Mass spectroscopy; Light effects; Accidents; Gas chromatography; Risk factors; Dose-response effects; Geriatrics; Body mass index; Dioxin; Puberty DO - http://dx.doi.org/10.1111/j.1365-2133.2005.06444.x ER - TY - JOUR T1 - Measurement of the Osmotic Properties of Thin Polymer Films and Biological Tissue Samples AN - 19425862; 6655040 AB - A new type of micro-osmometer is described in which water absorption of small tissue samples is measured by a quartz crystal microbalance (QCM). The swelling of the sample deposited on the surface of a quartz crystal is determined by monitoring the change in resonance frequency of the quartz sensor as a function of the vapor pressure in the surrounding environment. The measurement principle is verified by studying the water uptake of poly(vinyl alcohol) films. Reasonable agreement is found between the results obtained by the QCM-based osmometer and previous osmotic pressure measurements made on a similar poly(vinyl alcohol) sample. The feasibility of the new method is demonstrated by measuring the osmotic response of tissue-engineered cartilage samples. It is found that the osmotic pressure of cartilage substantially increases with culture time. The present result is consistent with cartilage models, suggesting that the proteoglycan content governs the compressive resistance of the tissue. JF - Biomacromolecules AU - Horkay, F AU - Horkayne-Szakaly, I AU - Basser, P J AD - Section on Tissue Biophysics and Biomimetics, Laboratory of Integrative and Medical Biophysics, NICHD, National Institutes of Health, 13 South Drive, Bethesda, Maryland 20892, USA Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 988 EP - 993 VL - 6 IS - 2 SN - 1525-7797, 1525-7797 KW - Biotechnology and Bioengineering Abstracts KW - Cartilage KW - Crystals KW - Tissue engineering KW - Osmotic pressure KW - Models KW - Water uptake KW - Proteoglycans KW - Vapors KW - Quartz KW - alcohols KW - Pressure KW - Films KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19425862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biomacromolecules&rft.atitle=Measurement+of+the+Osmotic+Properties+of+Thin+Polymer+Films+and+Biological+Tissue+Samples&rft.au=Horkay%2C+F%3BHorkayne-Szakaly%2C+I%3BBasser%2C+P+J&rft.aulast=Horkay&rft.aufirst=F&rft.date=2005-03-01&rft.volume=6&rft.issue=2&rft.spage=988&rft.isbn=&rft.btitle=&rft.title=Biomacromolecules&rft.issn=15257797&rft_id=info:doi/10.1021%2Fbm049332c LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Quartz; Cartilage; Films; alcohols; Crystals; Osmotic pressure; Proteoglycans; Water uptake; Vapors; Models; Tissue engineering; Pressure DO - http://dx.doi.org/10.1021/bm049332c ER - TY - JOUR T1 - Accurate measurement of super(15)N- super(13)C residual dipolar couplings in nucleic acids AN - 19420834; 6533554 AB - New 3D HCN quantitative J (QJ) pulse schemes are presented for the precise and accurate measurement of one-bond super(15)N sub(1/9)- super(13)C sub(1'), super(15)N sub(1/9)- super(13)C sub(6/8), and super(15)N sub(1/9)- super(13)C sub(2/4) residual dipolar couplings (RDCs) in weakly aligned nucleic acids. The methods employ super(1)H- super(13)C multiple quantum (MQ) coherence or TROSY-type pulse sequences for optimal resolution and sensitivity. RDCs are obtained from the intensity ratio of H sub(1')-C sub(1')-N sub(1/9) (MQ-HCN-QJ) or H sub(6/8)-C sub(6/8)-N sub(1/9) (TROSY-HCN-QJ) correlations in two interleaved 3D NMR spectra, with dephasing intervals of zero (reference spectrum) and similar to 1/(J2dNC (attenuated spectrum). The different types of super(15)N- super(13)C couplings can be obtained by using either the 3D MQ-HCN-QJ or TROSY-HCN-QJ pulse scheme, with the appropriate setting of the duration of the constant-time super(15)N evolution period and the offset of two frequency-selective super(13)C pulses. The methods are demonstrated for a uniformly super(13)C, super(15)N-enriched 24-nucleotide stem-loop RNA sequence, helix-35 psi , aligned in the magnetic field using phage Pf1. For measurements of RDCs systematic errors are found to be negligible, and experiments performed on a 1.5 mM helix-35 psi sample result in an estimated precision of ca. 0.07 Hz for super(1)D sub(NC), indicating the utility of the measured RDCs in structure validation and refinement. Indeed, for a complete set of super(15)N sub(1/9)- super(13)C sub(1'), super(15)N sub(1/9)- super(13)C sub(6/8), and super(15)N sub(1/9)- super(13)C sub(2/4) dipolar couplings obtained for the stem nucleotides, the measured RDCs are in excellent agreement with those predicted for an NMR structure of helix-35 psi , refined using independently measured observables, including super(13)C- super(1)H, super(13)C- super(13)C and super(1)H- super(1)H dipolar couplings. JF - Journal of Biomolecular NMR AU - Jaroniec, Christopher P AU - Boisbouvier, Jerome AU - Tworowska, Izabela AU - Nikonowicz, Edward P AU - Bax, Ad AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892-0520, USA Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 231 EP - 241 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 31 IS - 3 SN - 0925-2738, 0925-2738 KW - Biotechnology and Bioengineering Abstracts KW - Phages KW - Magnetic fields KW - nucleic acids KW - RNA KW - Nucleotide sequence KW - Phage Pf1 KW - N.M.R. KW - Evolution KW - Nucleotides KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19420834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biomolecular+NMR&rft.atitle=Accurate+measurement+of+super%2815%29N-+super%2813%29C+residual+dipolar+couplings+in+nucleic+acids&rft.au=Jaroniec%2C+Christopher+P%3BBoisbouvier%2C+Jerome%3BTworowska%2C+Izabela%3BNikonowicz%2C+Edward+P%3BBax%2C+Ad&rft.aulast=Jaroniec&rft.aufirst=Christopher&rft.date=2005-03-01&rft.volume=31&rft.issue=3&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+NMR&rft.issn=09252738&rft_id=info:doi/10.1007%2Fs10858-005-0646-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Phage Pf1; N.M.R.; nucleic acids; Magnetic fields; RNA; Nucleotides; Phages; Evolution; Nucleotide sequence DO - http://dx.doi.org/10.1007/s10858-005-0646-2 ER - TY - JOUR T1 - Neurodevelopmental and Growth Outcomes of Extremely Low Birth Weight Infants After Necrotizing Enterocolitis AN - 19412312; 6186004 AB - OBJECTIVES: Necrotizing enterocolitis (NEC) is a significant complication for the premature infant. However, subsequent neurodevelopmental and growth outcomes of extremely low birth weight (ELBW) infants with NEC have not been well described. We hypothesized that ELBW infants with surgically managed (SurgNEC) are at greater risk for poor neurodevelopmental and growth outcomes than infants with medically managed NEC (MedNEC) compared with infants without a history of NEC (NoNEC). The objective of this study was to compare growth, neurologic, and cognitive outcomes among ELBW survivors of SurgNEC and MedNEC with NoNEC at 18 to 22 months' corrected age. METHODS: Multicenter, retrospective analysis was conducted of infants who were born between January 1, 1995, and December 31, 1998, and had a birth weight <1000 g in the National Institute of Child Health and Human Development Neonatal Research Network Registry. Neurodevelopment and growth were assessed at 18 to 22 months' postmenstrual age. [Chi] super(2), t test, and logistic regression analyses were used. RESULTS: A total of 2948 infants were evaluated at 18 to 22 months, 124 of whom were SurgNEC and 121 of whom were MedNEC. Compared with NoNEC, both SurgNEC and MedNEC infants were of lower birth weight and had a greater incidence of late sepsis; SurgNEC but not MedNEC infants were more likely to have received a diagnosis of cystic periventricular leukomalacia and bronchopulmonary dysplasia and been treated with postnatal steroids. Weight, length, and head circumference <10 percentile at 18 to 22 months were significantly more likely among SurgNEC but not MedNEC compared with NoNEC infants. After correction for anthropometric measures at birth and adjusted age at follow-up, all growth parameters at 18 to 22 months for SurgNEC but not MedNEC infants were significantly less than for NoNEC infants. SurgNEC but not MedNEC was a significant independent risk factor for Mental Developmental Index <70 (odds ratio [OR]: 1.61; 95% confidence interval [CI]: 1.05-2.50), Psychomotor Developmental Index <70 (OR: 1.95; 95% CI: 1.25-3.04), and neurodevelopmental impairment (OR: 1.78; 95% CI: 1.17-2.73) compared with NoNEC. CONCLUSIONS: Among ELBW infants, SurgNEC is associated with significant growth delay and adverse neurodevelopmental outcomes at 18 to 22 months' corrected age compared with NoNEC. MedNEC does not seem to confer additional risk. SurgNEC is likely to be associated with greater severity of disease. JF - Pediatrics AU - Hintz, Susan R AU - Kendrick, Douglas E AU - Stoll, Barbara J AU - Vohr, Betty R AU - Fanaroff, Avroy A AU - Donovan, Edward F AU - Poole, WKenneth AU - Blakely, Martin L AU - Wright, Linda AU - Higgins, Rosemary AD - Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Palo Alto, California. Research Triangle Institute, Research Triangle Park, North Carolina. Department of Pediatrics, Emory University, Atlanta, Georgia. Department of Pediatrics, Women and Infants Hospital, Providence, RI. Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio. Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio. Department of Pediatric Surgery, University of Texas, Houston, TX. National Institute of Child Health and Human Development, Washington, DC Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 696 EP - 703 PB - American Academy of Pediatrics, 141 Northwest Point Blvd. Elk Grove Village IL 60007-1098 USA, [mailto:journals@aap.org], [URL:http://www.aap.org] VL - 115 IS - 3 SN - 0031-4005, 0031-4005 KW - Microbiology Abstracts B: Bacteriology; CSA Neurosciences Abstracts KW - Risk assessment KW - Neurodevelopmental disorders KW - Birth weight KW - Age KW - Dysplasia KW - Head KW - Necrotizing enterocolitis KW - Steroid hormones KW - Development KW - Sepsis KW - Cognitive ability KW - Risk factors KW - Regression analysis KW - Neonates KW - periventricular leukomalacia KW - Infants KW - N3 11003:Developmental neuroscience KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19412312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Neurodevelopmental+and+Growth+Outcomes+of+Extremely+Low+Birth+Weight+Infants+After+Necrotizing+Enterocolitis&rft.au=Hintz%2C+Susan+R%3BKendrick%2C+Douglas+E%3BStoll%2C+Barbara+J%3BVohr%2C+Betty+R%3BFanaroff%2C+Avroy+A%3BDonovan%2C+Edward+F%3BPoole%2C+WKenneth%3BBlakely%2C+Martin+L%3BWright%2C+Linda%3BHiggins%2C+Rosemary&rft.aulast=Hintz&rft.aufirst=Susan&rft.date=2005-03-01&rft.volume=115&rft.issue=3&rft.spage=696&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Neurodevelopmental disorders; Risk assessment; Birth weight; Age; Head; Dysplasia; Necrotizing enterocolitis; Development; Steroid hormones; Sepsis; Cognitive ability; Risk factors; Regression analysis; Neonates; Infants; periventricular leukomalacia ER - TY - JOUR T1 - Improvement of Motor Function with Noninvasive Cortical Stimulation in a Patient with Chronic Stroke AN - 19409002; 6176653 AB - This manuscript reports the effects of transcranial DC stimulation (tDCS), a technique that enhances cortical plasticity in healthy humans, on motor function in a patient with chronic subcortical ischemic stroke. tDCS but not sham applied in a double-blind protocol to motor regions of the affected hemisphere led to improvements in pinch force, Jebsen-Taylor Hand Function Test, and simple reaction times in the paretic hand that outlasted the stimulation period for at least 40 min. These changes were accompanied by increased corticomotor excitability identified by enhanced recruitment curves and reduced intracortical inhibition to transcranial magnetic stimulation. These results document a beneficial effect of noninvasive brain stimulation on motor function in a human patient with stroke and raise the hypothesis of its potential application in neurorehabilitation. JF - Neurorehabilitation and Neural Repair AU - Hummel, Friedhelm AU - Cohen, Leonardo G AD - Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, Cortical Physiology Research Group, Department of Neurology, and Hertie Institute for Clinical Brain Research, Eberhard-Karls University Tuebingen, Tuebingen, Germany Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 14 EP - 19 PB - Sage Publications, Inc., 2455 Teller Road Thousand Oaks CA 91320 USA, [mailto:info@sagepub.com], [URL:http://www.sagepub.com/] VL - 19 IS - 1 SN - 1545-9683, 1545-9683 KW - Physical Education Index; CSA Neurosciences Abstracts KW - Hands KW - Recruitment KW - Plasticity (cortical) KW - Stroke KW - Brain KW - Hand KW - Motor performance tests KW - Techniques KW - Patients KW - Health KW - Ischemia KW - Excitability KW - Inhibition KW - Reaction time KW - Transcranial magnetic stimulation KW - Cortex KW - Reaction time task KW - Stimuli KW - PE 110:Physical Therapy KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19409002?accountid=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=Neurorehabilitation+and+Neural+Repair&rft.atitle=Improvement+of+Motor+Function+with+Noninvasive+Cortical+Stimulation+in+a+Patient+with+Chronic+Stroke&rft.au=Hummel%2C+Friedhelm%3BCohen%2C+Leonardo+G&rft.aulast=Hummel&rft.aufirst=Friedhelm&rft.date=2005-03-01&rft.volume=19&rft.issue=1&rft.spage=14&rft.isbn=&rft.btitle=&rft.title=Neurorehabilitation+and+Neural+Repair&rft.issn=15459683&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2007-01-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Reaction time; Hands; Stroke; Brain; Techniques; Motor performance tests; Stimuli; Health; Patients; Inhibition; Transcranial magnetic stimulation; Cortex; Reaction time task; Plasticity (cortical); Recruitment; Hand; Ischemia; Excitability ER - TY - JOUR T1 - Manganese-enhanced magnetic resonance imaging of mouse brain after systemic administration of MnCl sub(2): Dose-dependent and temporal evolution of T sub(1) contrast AN - 19408111; 6499405 AB - Manganese is a useful contrast agent for MRI of animals. Previously, it has been shown that systemic doses of MnCl sub(2) provide unique contrast in the rodent brain, enabling visualization of neuroarchitecture. The present work investigates the dose and temporal dependence of brain enhancement after i.v. administration of MnCl sub(2). Varying doses of MnCl sub(2) (9-175 mg/kg) were administered to mice from 0 to 24 h prior to T sub(1)-weighted manganese-enhanced MRI (MEMRI) at 11.7 T. Pre-MnCl sub(2) T sub(1) values measured in different brain regions ranged from 1.17 plus or minus 0.03 to 1.76 plus or minus 0.01 s. Post-MnCl sub(2) T sub(1) measured 24 hr after administration of MnCl sub(2) were significantly decreased, even after the lowest dose of MnCl sub(2). The largest decreases occurred in the pituitary gland, where post-MnCl sub(2) T sub(1) ranged from 231 plus or minus 23 ms following the lowest dose to 143 plus or minus 43 ms after the highest dose, while the smallest decreases were observed in cortex (post-MnCl sub(2) T sub(1) = 1060 plus or minus 5 ms for low dose and 637 plus or minus 5 ms for high dose). The contrast resulting after 14 hr did not change up to 24 hr. Enhancement first occurred in subarachnoid spaces, followed by ventricles and periventricular tissues, and finally reached the remainder of the brain. Cortical layers were detected at higher doses (>88 mg/kg) and olfactory bulb layers were detected with the lowest dose (9 mg/kg). Temporal evolution of the enhancement of the olfactory bulb layers was observed. In some regions of the brain, such as hippocampus and thalamus, the changes in contrast detected between 2 and 14 hr used very specific pathways. These results demonstrate that both the dose and the time after MnCl sub(2) can be manipulated to optimize brain contrast in a region-specific manner. JF - Magnetic Resonance in Medicine AU - Lee, Jung Hee AU - Silva, Afonso C AU - Merkle, Hellmut AU - Koretsky, Alan P AD - Laboratory of Functional and Molecular Imaging, National Institutes of Neurological Disorders and Stroke, 10 Center Drive, Building 10 Room B1D118, Bethesda, MD 20892-1065, USA, KoretskyA@ninds.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 640 EP - 648 PB - John Wiley & Sons, Ltd. VL - 53 IS - 3 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts KW - Neuroimaging KW - Hippocampus KW - Magnetic resonance imaging KW - Brain KW - subarachnoid space KW - Thalamus KW - Olfactory bulb KW - Cortex KW - Pituitary KW - Contrast media KW - N.M.R. KW - Manganese KW - Evolution KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19408111?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Manganese-enhanced+magnetic+resonance+imaging+of+mouse+brain+after+systemic+administration+of+MnCl+sub%282%29%3A+Dose-dependent+and+temporal+evolution+of+T+sub%281%29+contrast&rft.au=Lee%2C+Jung+Hee%3BSilva%2C+Afonso+C%3BMerkle%2C+Hellmut%3BKoretsky%2C+Alan+P&rft.aulast=Lee&rft.aufirst=Jung&rft.date=2005-03-01&rft.volume=53&rft.issue=3&rft.spage=640&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20368 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Brain; Magnetic resonance imaging; Evolution; Olfactory bulb; Cortex; Hippocampus; Neuroimaging; Thalamus; Pituitary; N.M.R.; subarachnoid space; Manganese; Contrast media DO - http://dx.doi.org/10.1002/mrm.20368 ER - TY - JOUR T1 - Montanide super([registeredsign]) ISA 720 vaccines: quality control of emulsions, stability of formulated antigens, and comparative immunogenicity of vaccine formulations AN - 17863641; 6202451 AB - Montanide super([registeredsign]) ISA 720 is an experimental adjuvant, formulated as water-in-oil emulsions, that induces high antibody titers in several animal species. It has been used in human vaccine trials with malaria and HIV vaccines. The heightened response is likely due, in part, to the formation of a depot at the injection site. However, post-formulation modifications were seen with seven proteins tested during storage of ISA 720 formulations at 37 C for 1 week and two proteins stored longer at 4 C. Potency studies in mice, in which the stored vaccines were diluted into placebo emulsions for appropriate dosing, indicated that this instability could lead to loss of immunogenicity in the post-injection depot, limiting the allowable storage time of preformed vaccines. We describe point-of-injection formulation for ISA 720 vaccines that meets the requirement for in vitro stability. For preformed vaccines, addition of glycine or glycylglycine prevented antigen modification on storage at 37 C, providing a potential way of stabilizing antigen/ISA 720 formulations for in vitro storage and the post-injection depot. JF - Vaccine AU - Miles, A P AU - McClellan, HA AU - Rausch, K M AU - Zhu, D AU - Whitmore, MD AU - Singh, S AU - Martin, L B AU - Wu, Y AU - Giersing, B K AU - Stowers, A W AU - Long, CA AU - Saul, A AD - Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5640 Fishers Lane, Twinbrook I Room 1118, Rockville, MD 20852, USA, amiles@niaid.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 2530 EP - 2539 PB - Butterworth-Heinemann, 313 Washington St. Newton MA 02158 USA VL - 23 IS - 19 SN - 0264-410X, 0264-410X KW - HIV KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Glycine KW - Malaria KW - Adjuvants KW - Antibodies KW - Immunogenicity KW - Human immunodeficiency virus KW - Quality control KW - Vaccines 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/17863641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Montanide+super%28%5Bregisteredsign%5D%29+ISA+720+vaccines%3A+quality+control+of+emulsions%2C+stability+of+formulated+antigens%2C+and+comparative+immunogenicity+of+vaccine+formulations&rft.au=Miles%2C+A+P%3BMcClellan%2C+HA%3BRausch%2C+K+M%3BZhu%2C+D%3BWhitmore%2C+MD%3BSingh%2C+S%3BMartin%2C+L+B%3BWu%2C+Y%3BGiersing%2C+B+K%3BStowers%2C+A+W%3BLong%2C+CA%3BSaul%2C+A&rft.aulast=Miles&rft.aufirst=A&rft.date=2005-03-01&rft.volume=23&rft.issue=19&rft.spage=2530&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2Fj.vaccine.2004.08.049 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Vaccines; Immunogenicity; Glycine; Antibodies; Malaria; Adjuvants; Quality control DO - http://dx.doi.org/10.1016/j.vaccine.2004.08.049 ER - TY - JOUR T1 - Factors Characterizing Staphylococcus epidermidis Invasiveness Determined by Comparative Genomics AN - 17853618; 6169388 AB - Virulence mechanisms of the leading nosocomial pathogen Staphylococcus epidermidis are poorly understood. We used microarray-based genome-wide comparison of clinical and commensal S. epidermidis strains to identify putative virulence determinants. Our study revealed high genetic variability of the S. epidermidis genome, new markers for invasiveness of S. epidermidis, and potential targets for drug development against S. epidermidis infections. JF - Infection and Immunity AU - Yao, Yufeng AU - Sturdevant, Daniel E AU - Villaruz, Amer AU - Xu, Lin AU - Gao, Qian AU - Otto, Michael AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Hamilton, Montana. Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai, China Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 1856 EP - 1860 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 73 IS - 3 SN - 0019-9567, 0019-9567 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Virulence KW - Invasiveness KW - Commensals KW - Genetic diversity KW - Drug development KW - Pathogens KW - genomics KW - Infection KW - Staphylococcus epidermidis KW - Lead KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17853618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Factors+Characterizing+Staphylococcus+epidermidis+Invasiveness+Determined+by+Comparative+Genomics&rft.au=Yao%2C+Yufeng%3BSturdevant%2C+Daniel+E%3BVillaruz%2C+Amer%3BXu%2C+Lin%3BGao%2C+Qian%3BOtto%2C+Michael&rft.aulast=Yao&rft.aufirst=Yufeng&rft.date=2005-03-01&rft.volume=73&rft.issue=3&rft.spage=1856&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Virulence; Invasiveness; Commensals; Genetic diversity; Drug development; genomics; Pathogens; Infection; Lead; Staphylococcus epidermidis ER - TY - JOUR T1 - Hepatic DNA adduct dosimetry in rats fed tamoxifen: a comparison of methods AN - 17846589; 6246550 AB - Liver homogenates from rats fed tamoxifen (TAM) in the diet were shared among four different laboratories. TAM-DNA adducts were assayed by high pressure liquid chromatography-electrospray tandem mass spectrometry (HPLC-ES-MS/MS), TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), and super(32)P-postlabeling with either thin layer ( super(32)P-P-TLC) or liquid chromatography ( super(32)P-P-HPLC) separation. In the first study, rats were fed a diet containing 500 p.p.m. TAM for 2 months, and the values for measurements of the (E)- alpha -(deoxyguanosin-N super(2)-yl)-tamoxifen (dG-N super(2)-TAM) adduct in replicate rat livers varied by 3.5-fold when quantified using 'in house' TAM-DNA standards, or other approaches where appropriate. In the second study, rats were fed 0, 50, 250 or 500 p.p.m. TAM for 2 months, and TAM-DNA values were quantified using both 'in house' approaches as well as a newly synthesized [N-methyl- super(3)H]TAM-DNA standard that was shared among all the participating groups. In the second study, the total TAM-DNA adduct values varied by 2-fold, while values for the dG-N super(2)-TAM varied by 2.5-fold. Ratios of dG-N super(2)-TAM:(E)- alpha -(deoxyguanosin-N super(2)-yl)-N-desmethyltamoxifen (dG-N super(2)-N-desmethyl-TAM) in the second study were similar to 1:1 over the range of doses examined. The study demonstrated a remarkably good agreement for TAM-DNA adduct measurements among the diverse methods employed. JF - Mutagenesis AU - Schild, Laura J AU - Phillips, David H AU - Osborne, Martin R AU - Hewer, Alan AU - Beland, Frederick A AU - Churchwell, Mona I AU - Brown, Karen AU - Gaskell, Margaret AU - Wright, Elizabeth AU - Poirier, Miriam C AD - Carcinogen-DNA Interactions Section, National Cancer Institute, Building 37, Room 4032 NIH, 37 Convent Drive MSC-4255, Bethesda, MD 20892-4255, USA Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 115 EP - 124 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 20 IS - 2 SN - 0267-8357, 0267-8357 KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - Diets KW - DNA adducts KW - Houses KW - Adducts KW - Dosimetry KW - Tamoxifen KW - Mutagenesis KW - Liquid chromatography KW - Liver KW - Chemiluminescence KW - Pressure KW - Immunoassays KW - X 24117:Biochemistry KW - N 14035:DNA: Direct modification or damage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17846589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutagenesis&rft.atitle=Hepatic+DNA+adduct+dosimetry+in+rats+fed+tamoxifen%3A+a+comparison+of+methods&rft.au=Schild%2C+Laura+J%3BPhillips%2C+David+H%3BOsborne%2C+Martin+R%3BHewer%2C+Alan%3BBeland%2C+Frederick+A%3BChurchwell%2C+Mona+I%3BBrown%2C+Karen%3BGaskell%2C+Margaret%3BWright%2C+Elizabeth%3BPoirier%2C+Miriam+C&rft.aulast=Schild&rft.aufirst=Laura&rft.date=2005-03-01&rft.volume=20&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Mutagenesis&rft.issn=02678357&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Diets; DNA adducts; Houses; Liquid chromatography; Adducts; Dosimetry; Liver; Pressure; Chemiluminescence; Immunoassays; Tamoxifen; Mutagenesis ER - TY - JOUR T1 - Digital biology: an emerging and promising discipline AN - 17837347; 6213464 AB - This article examines the role of computation and quantitative methods in modern biomedical research to identify emerging scientific, technical, policy and organizational trends. It identifies common concerns and practices in the emerging community of computationally-oriented bio-scientists by reviewing a national symposium, Digital Biology: the Emerging Paradigm, held at the National Institutes of Health in Bethesda, Maryland, November 6 super(t) super(h) and 7 super(t) super(h) 2003. This meeting showed how biomedical computing promises scientific breakthroughs that will yield significant health benefits. Three key areas that define the emerging discipline of digital biology are: scientific data integration, multi-scale modeling and networked science. Each area faces unique technical challenges and information policy issues that must be addressed as the field matures. Here we summarize the emergent challenges and offer suggestions to academia, industry and government on how best to expand the role of computation in their scientific activities. JF - Trends in Biotechnology AU - Morris, R W AU - Bean, CA AU - Farber, G K AU - Gallahan, D AU - Jakobsson, E AU - Liu, Y AU - Lyster, P M AU - Peng, GCY AU - Roberts, F S AU - Twery, M AU - Whitmarsh, J AU - Skinner, K Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 113 EP - 117 VL - 23 IS - 3 SN - 0167-7799, 0167-7799 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Reviews KW - Computer applications KW - Data acquisition KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W3 33080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17837347?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Biotechnology&rft.atitle=Digital+biology%3A+an+emerging+and+promising+discipline&rft.au=Morris%2C+R+W%3BBean%2C+CA%3BFarber%2C+G+K%3BGallahan%2C+D%3BJakobsson%2C+E%3BLiu%2C+Y%3BLyster%2C+P+M%3BPeng%2C+GCY%3BRoberts%2C+F+S%3BTwery%2C+M%3BWhitmarsh%2C+J%3BSkinner%2C+K&rft.aulast=Morris&rft.aufirst=R&rft.date=2005-03-01&rft.volume=23&rft.issue=3&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Trends+in+Biotechnology&rft.issn=01677799&rft_id=info:doi/10.1016%2Fj.tibtech.2005.01.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Data acquisition; Computer applications DO - http://dx.doi.org/10.1016/j.tibtech.2005.01.005 ER - TY - JOUR T1 - Unique patterns of gene expression changes in liver after treatment of mice for 2 weeks with different known carcinogens and non-carcinogens AN - 17836219; 6167264 AB - Previously we demonstrated that the mouse liver tumor response to the non- genotoxic carcinogens oxazepam and Wyeth-14,643 involved more differences than similarities in changes in early gene expression. In this study we used quantitative real-time PCR and oligonucleotide microarray analysis to identify genes that were up-or down-regulated in mouse liver early after treatment with different known carcinogens, including oxazepam (125 and 2500 p.p.m.), o- nitrotoluene (1250 and 5000 p.p.m.) and methyleugenol (75 mg/kg/day), or the non-carcinogens p-nitrotoluene (5000 p.p.m.), eugenol (75 mg/kg/day) and acetaminophen (6000 p.p.m.). Starting at 6 weeks of age, mice were treated with the different compounds for 2 weeks in the diet, at which time the livers were collected. First, expression of 12 genes found previously to be altered in liver after 2 weeks treatment with oxazepam and/or Wyeth-14,643 was examined in livers from the various chemical treatment groups. These gene expression changes were confirmed for the livers from the oxazepam-treated mice in the present study, but were not good early markers for all the carcinogens in this study. In addition, expression of 20 842 genes was assessed by oligonucleotide microarray [n = 4 livers/group, 2 hybridizations/liver (with fluor reversals)] and the results were analyzed using the Rosetta Resolver System and GeneSpring software. The analyses revealed that several cancer-related genes, including Fhit, Wwox, Tsc-22 and Gadd45b, were induced or repressed in unique patterns for specific carcinogens and not altered by the non-carcinogens. The data indicate that even if the tumor response, including molecular alterations, is similar, such as for oxazepam and methyleugenol, early gene expression changes appear to be carcinogen specific and seem to involve apoptosis and cell cycle-related genes. JF - Carcinogenesis AU - Iida, Mari AU - Anna, Colleen H AU - Holliday, Wanda M AU - Collins, Jennifer B AU - Cunningham, Michael L AU - Sills, Robert C AU - Devereux, Theodora R AD - Laboratory of Molecular Carcinogenesis, National Center for Toxicogenomics, Laboratory of Pharmacology and Chemistry and Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 689 EP - 699 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 26 IS - 3 SN - 0143-3334, 0143-3334 KW - Mice KW - Wyeth-14,643 KW - methyleugenol KW - oxazepam KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Diets KW - Apoptosis KW - Genotoxicity KW - Cell cycle KW - Carcinogens KW - Oligonucleotides KW - Gene expression KW - Computer programs KW - Carcinogenesis KW - Liver KW - Polymerase chain reaction KW - eugenol KW - Acetaminophen KW - X 24240:Miscellaneous KW - N 14010:Physical & Computer Methods & Assays UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17836219?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Unique+patterns+of+gene+expression+changes+in+liver+after+treatment+of+mice+for+2+weeks+with+different+known+carcinogens+and+non-carcinogens&rft.au=Iida%2C+Mari%3BAnna%2C+Colleen+H%3BHolliday%2C+Wanda+M%3BCollins%2C+Jennifer+B%3BCunningham%2C+Michael+L%3BSills%2C+Robert+C%3BDevereux%2C+Theodora+R&rft.aulast=Iida&rft.aufirst=Mari&rft.date=2005-03-01&rft.volume=26&rft.issue=3&rft.spage=689&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Diets; Apoptosis; Cell cycle; Genotoxicity; Carcinogens; Oligonucleotides; Gene expression; Computer programs; Carcinogenesis; Liver; eugenol; Polymerase chain reaction; Acetaminophen ER - TY - JOUR T1 - Amalgam Exposure And Neurological Function AN - 17831311; 6160849 AB - Concerns regarding the safety of silver-mercury amalgam fillings continue to be raised in the absence of any direct evidence of harm. The widespread population exposure to amalgam mandated that a thorough investigation be conducted of its potential effects on the nervous system. The National Institute of Dental and Craniofacial Research and U.S. Air Force investigators collaborated in the ongoing Air Force Health Study (AFHS) of Vietnam era veterans. The primary study question involved adverse health effects associated with exposure to herbicides or dioxin. An assessment of exposure to dental amalgam fillings was added to the 1997-1998 health examination to investigate possible associations between amalgam exposure and neurological abnormalities. Our study population consisted of 1663 dentate AFHS participants, comprised of 986 AFHS controls and 677 Ranch Hand veterans who were exposed to dioxin in Vietnam. Two hundred and fifty-two of the participants had confirmed diabetes mellitus. Study outcomes included clinical neurological signs, vibrotactile thresholds, and summary variables for different levels of peripheral neuropathy. A limitation of our study is that our database did not include more sensitive continuous measures such as nerve conduction studies. No significant associations were found between amalgam exposure and clinical neurological signs of abnormal tremor, coordination, station or gait, strength, sensation, or muscle stretch reflexes or for any level of peripheral neuropathy among our study participants. A statistically significant association was detected between amalgam exposure and the continuous vibrotactile sensation response for the combined non-diabetic participants and separately for non-diabetic AFHS controls. No significant association in this measure was detectable for non-diabetic Ranch Hand veterans or among the combined diabetic participants. The association is a sub-clinical finding that was not associated with symptoms, clinically evident signs of neuropathy, or any functional impairment. Overall, we found no association between amalgam exposure and neurological signs or clinically evident peripheral neuropathy. Our findings do not support the hypothesis that exposure to amalgam produces adverse, clinically evident neurological effects. JF - Neurotoxicology AU - Kingman, A AU - Albers, J W AU - Arezzo, J C AU - Garabrant, D H AU - Michalek, JE Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 241 EP - 255 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 26 IS - 2 SN - 0161-813X, 0161-813X KW - amalgam KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - Amalgam exposure KW - Mercury KW - Neurological signs KW - Peripheral neuropathy KW - Epidemiology KW - Teeth KW - Muscle contraction KW - Statistical analysis KW - Muscles KW - Hand KW - Population studies KW - Herbicides KW - Diabetes mellitus KW - Databases KW - Dental caries KW - Nervous system KW - Stretch reflex KW - gait KW - Nerve conduction KW - tremor KW - Dioxin KW - Neuropathy KW - X 24166:Environmental impact KW - N3 11105:Primates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17831311?accountid=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=Amalgam+Exposure+And+Neurological+Function&rft.au=Kingman%2C+A%3BAlbers%2C+J+W%3BArezzo%2C+J+C%3BGarabrant%2C+D+H%3BMichalek%2C+JE&rft.aulast=Kingman&rft.aufirst=A&rft.date=2005-03-01&rft.volume=26&rft.issue=2&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/10.1016%2Fj.neuro.2004.09.008 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Teeth; Muscle contraction; Muscles; Statistical analysis; Population studies; Hand; Herbicides; Diabetes mellitus; Dental caries; Databases; Nervous system; Peripheral neuropathy; Mercury; Stretch reflex; Nerve conduction; gait; tremor; Dioxin; Neuropathy DO - http://dx.doi.org/10.1016/j.neuro.2004.09.008 ER - TY - JOUR T1 - Meat intake, cooking-related mutagens and risk of colorectal adenoma in a sigmoidoscopy-based case-control study AN - 17831133; 6167249 AB - Reported habits of red meat consumption, particularly red meat that has been cooked to the degree termed 'well-done', is a positive risk factor for colorectal cancer. Under high, pyrolytic temperatures, heterocyclic amines (HCA) and benzoapyrene (BP) molecules can form inside and on the surface of red meat, respectively. These compounds are precursors that are metabolically converted to compounds known to act as mutagens and carcinogens in animal models, yet their role in human colorectal carcinogenesis remains to be clarified. We investigated whether intake of these compounds is associated with risk of colorectal adenoma in the context of a polyp-screening study conducted in Southern California. Using a database of individual HCAs and BP in meats of various types and subjected to specified methods and degrees of cooking, we estimated nanogram consumption of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine, 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline, 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline and benzoapyrene (BP). We observed a 6% increased risk of large (>1 cm) adenoma per 10 ng/day consumption of BP [OR = 1.06 (95% CI, 1.00-1.12), P (trend) = 0.04]. A major source of BP is red meat exposed to a naked flame, as occurs during the barbecuing process. Consistent with this finding an incremental increase of 10 g of barbecued red meat per day was associated with a 29% increased risk of large adenoma [OR = 1.29 (95% CI, 1.02-1.63), P (trend) = 0.04]. Individuals in the top quintile of barbecued red meat intake were at increased risk of large adenoma [OR = 1.90 (95% CI, 1.04- 3.45)], compared with never consuming barbecued red meat. The consumption of oven-broiled red meat was inversely related to adenoma risk compared with non- consumers [OR = 0.49 (95% CI, 0.28-0.85)]. We did not identify any association with consumption of individual HCAs and colorectal adenoma risk. These results support the hypothesis that BP contributes to colorectal carcinogenesis. JF - Carcinogenesis AU - Gunter, Marc J AU - Probst-Hensch, Nicole M AU - Cortessis, Victoria K AU - Kulldorff, Martin AU - Haile, Robert W AU - Sinha, Rashmi AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, EPS, 6120 Executive Boulevard, Rockville, MD Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 637 EP - 642 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 26 IS - 3 SN - 0143-3334, 0143-3334 KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Temperature effects KW - Heterocyclic amines KW - Mutagens KW - Colorectal cancer KW - Animal models KW - Carcinogens KW - Meat KW - Databases KW - Risk factors KW - Carcinogenesis KW - Cooking KW - quinoxaline KW - Consumers KW - Adenoma KW - X 24120:Food, additives & contaminants KW - N 14035:DNA: Direct modification or damage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17831133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Meat+intake%2C+cooking-related+mutagens+and+risk+of+colorectal+adenoma+in+a+sigmoidoscopy-based+case-control+study&rft.au=Gunter%2C+Marc+J%3BProbst-Hensch%2C+Nicole+M%3BCortessis%2C+Victoria+K%3BKulldorff%2C+Martin%3BHaile%2C+Robert+W%3BSinha%2C+Rashmi&rft.aulast=Gunter&rft.aufirst=Marc&rft.date=2005-03-01&rft.volume=26&rft.issue=3&rft.spage=637&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Temperature effects; Mutagens; Heterocyclic amines; Animal models; Colorectal cancer; Carcinogens; Meat; Databases; Risk factors; Cooking; Carcinogenesis; quinoxaline; Consumers; Adenoma ER - TY - JOUR T1 - Identification of Mycobacterium Species by secA1 Sequences AN - 17830701; 6190279 AB - We describe a novel molecular method for the differentiation and identification of 29 mycobacterial species. The target is the secA1 gene that codes for the essential protein SecA1, a key component of the major pathway of protein secretion across the cytoplasmic membrane. A 700-bp region of the secA1 gene was amplified and sequenced from 47 American Type Culture Collection strains of 29 Mycobacterium species as well as from 59 clinical isolates. Sequence variability in the amplified segment of the secA1 gene allowed the differentiation of all species except for the members of the Mycobacterium tuberculosis (MTB) complex, which had identical sequences. A range of 83.3 to 100% interspecies similarity was observed. All species could also be differentiated by their amino acid sequences as deduced from the sequenced region of the secA1 gene, with the exception of the MTB complex. Partial sequences of secA1 from clinical isolates belonging to nine frequently isolated species of mycobacteria revealed a very high intraspecies similarity at the DNA level (typically >99%; range, 96.0 to 100%); all clinical isolates were correctly identified. Comparison of the deduced 233-amino-acid sequences among clinical isolates of the same species showed between 99.6 and 100% similarity. To our knowledge, this is the first time a secretion-related gene has been used for the identification of the species within a bacterial genus. JF - Journal of Clinical Microbiology AU - Zelazny, Adrian M AU - Calhoun, Leslie B AU - Li, Li AU - Shea, Yvonne R AU - Fischer, Steven H AD - Microbiology Service, Department of Laboratory Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 1051 EP - 1058 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 43 IS - 3 SN - 0095-1137, 0095-1137 KW - SecA1 protein KW - Microbiology Abstracts B: Bacteriology KW - Clinical isolates KW - Differentiation KW - Amino acids KW - Nucleotide sequence KW - Secretion KW - Cytoplasmic membranes KW - DNA KW - American Type Culture Collection KW - Mycobacterium tuberculosis KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17830701?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Identification+of+Mycobacterium+Species+by+secA1+Sequences&rft.au=Zelazny%2C+Adrian+M%3BCalhoun%2C+Leslie+B%3BLi%2C+Li%3BShea%2C+Yvonne+R%3BFischer%2C+Steven+H&rft.aulast=Zelazny&rft.aufirst=Adrian&rft.date=2005-03-01&rft.volume=43&rft.issue=3&rft.spage=1051&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Clinical isolates; Differentiation; Secretion; American Type Culture Collection; Amino acids; DNA; Cytoplasmic membranes; Nucleotide sequence ER - TY - JOUR T1 - Induction of preneoplastic lung lesions in guinea pigs by cigarette smoke inhalation and their exacerbation by high dietary levels of vitamins C and E AN - 17805750; 6167240 AB - The development of effective chemopreventive agents against cigarette smoke- induced lung cancer could be greatly facilitated by the availability of suitable laboratory animal models. Here we report that male Hartley guinea pigs treated with cigarette smoke by inhalation twice a day for 28 days developed preneoplastic lung lesions, including bronchial hyperplasia, dysplasia and squamous metaplasia, analogous to those found in human smokers. The lesions were accompanied by increased expression of proliferating cell nuclear antigen and activation of the serine/threonine kinase Akt in the bronchial epithelium. In contrast, no lung lesions were found in guinea pigs ('sham smoked') that were submitted to identical procedures but without cigarettes. Compared with a diet low in vitamin C (50 p.p.m.) and vitamin E (15 p.p.m.), a diet high in vitamin C (4000 p.p.m.) and vitamin E (40 p.p.m.) significantly increased the incidence of these lesions. The inclusion of 1,4-phenylenebis(methylene)selenocyanate (p- XSC), a synthetic chemopreventive organoselenium compound, in the high vitamin C-high vitamin E diet at a level of 15 p.p.m. as selenium appeared to decrease the lesion incidence. Administration of (-)-epigallocatechin gallate, a powerful green tea polyphenolic antioxidant, at 560 p.p.m. in the drinking water had no effect. As in human smokers, levels of ascorbate in blood plasma, lung, liver and the adrenal glands were significantly decreased by cigarette smoke inhalation. These results identify a relevant in vivo laboratory model of cigarette smoke-induced lung cancer, suggest that p-XSC may have activity as a chemopreventive agent against cigarette smoke-induced lung lesions and provide additional evidence that very high dietary levels of certain antioxidants can have co-carcinogenic activity in cigarette smoke-induced lung cancer. JF - Carcinogenesis AU - Fiala, Emerich S AU - Sohn, Ock Soon AU - Wang, Chung-Xiou AU - Seibert, Eleanore AU - Tsurutani, Junji AU - Dennis, Phillip A AU - El-Bayoumy, Karam AU - Sodum, Rama S AU - Desai, Dhimant AU - Reinhardt, Joel AU - Aliaga, Cesar AD - Institute for Cancer Prevention, Valhalla, NY, USA and Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 605 EP - 612 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 26 IS - 3 SN - 0143-3334, 0143-3334 KW - 1,4-phenylenebis(methylene)selenocyanate KW - guinea pigs KW - Toxicology Abstracts KW - Inhalation KW - Diets KW - Antioxidants KW - Protein-serine/threonine kinase KW - green tea KW - Laboratory animals KW - Cigarette smoke KW - Proliferating cell nuclear antigen KW - epigallocatechin gallate KW - Ascorbic acid KW - Hyperplasia KW - Vitamin E KW - Metaplasia KW - Vitamins KW - Carcinogenesis KW - AKT protein KW - chemopreventive agents KW - Drinking water KW - Lung cancer KW - X 24120:Food, additives & contaminants KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17805750?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Induction+of+preneoplastic+lung+lesions+in+guinea+pigs+by+cigarette+smoke+inhalation+and+their+exacerbation+by+high+dietary+levels+of+vitamins+C+and+E&rft.au=Fiala%2C+Emerich+S%3BSohn%2C+Ock+Soon%3BWang%2C+Chung-Xiou%3BSeibert%2C+Eleanore%3BTsurutani%2C+Junji%3BDennis%2C+Phillip+A%3BEl-Bayoumy%2C+Karam%3BSodum%2C+Rama+S%3BDesai%2C+Dhimant%3BReinhardt%2C+Joel%3BAliaga%2C+Cesar&rft.aulast=Fiala&rft.aufirst=Emerich&rft.date=2005-03-01&rft.volume=26&rft.issue=3&rft.spage=605&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Ascorbic acid; Vitamin E; Diets; Lung cancer; Inhalation; Cigarette smoke; chemopreventive agents; Antioxidants; Vitamins; Drinking water; Hyperplasia; Proliferating cell nuclear antigen; AKT protein; Protein-serine/threonine kinase; Laboratory animals; Carcinogenesis; Metaplasia; epigallocatechin gallate; green tea ER - TY - JOUR T1 - Apoptotic volume decrease and nitric oxide AN - 17774382; 6149262 AB - Apoptosis is a physiological cell death process whose well-defined characteristics distinguish it from more accidental cell death processes. The loss of cell volume, or cell shrinkage, recently termed apoptotic volume decrease (AVD), is considered a hallmark of the apoptotic process. The activation and/or repression of the AVD process has been shown to be quite complex during apoptosis, with the involvement of multiple ionic transport mechanisms acting in both a cell type and stimulus specific manner. Similarly, the role of nitric oxide (NO) during apoptosis has also been shown to be just as complex, specifically in its ability to either induce and/or prevent apoptosis. This review examines current evidence for a link between AVD and NO and how they may interact during the programmed cell death process. JF - Toxicology AU - Bortner, C D AD - The Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Department of Health and Human Services, National Institutes of Health, Research Triangle Park, NC 27709, USA, bortner@niehs.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 213 EP - 221 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 208 IS - 2 SN - 0300-483X, 0300-483X KW - Toxicology Abstracts KW - Cell death KW - Apoptosis KW - Reviews KW - Cell size KW - Atrophy KW - Nitric oxide KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17774382?accountid=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=Apoptotic+volume+decrease+and+nitric+oxide&rft.au=Bortner%2C+C+D&rft.aulast=Bortner&rft.aufirst=C&rft.date=2005-03-01&rft.volume=208&rft.issue=2&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2Fj.tox.2004.11.024 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Apoptosis; Cell death; Nitric oxide; Reviews; Cell size; Atrophy DO - http://dx.doi.org/10.1016/j.tox.2004.11.024 ER - TY - JOUR T1 - Nitric oxide and chemically induced hepatotoxicity: beneficial effects of the liver-selective nitric oxide donor, V-PYRRO/NO AN - 17766027; 6149264 AB - Nitric oxide (NO) is endogenously produced by the enzyme NO synthase in the cell or pharmacologically delivered to tissues as NO prodrugs. This simple molecule is a potent biological mediator in a myriad of physiological and pathological events. The liver plays a central role in metabolism and immune processes, and is a major target organ influenced by NO. NO production in the liver is usually increased in response to acute insult with hepatotoxicants, and may be decreased during chronic liver diseases. The induction of NO production could be envisioned as an early adaptive response, which may become a mediator of tissue damage when in excess. In this regard, inhibition of endogenous NO synthase has been shown to be beneficial in some cases and detrimental in others. The creation of eNOS and iNOS knockout animals has advanced our understanding of NO function in hepatic response to toxic insults. Knocking endogenous NO production can be beneficial in response to certain toxicants; however, in general it weakens the body's defense mechanisms against toxic insults. A variety of pharmacological NO prodrugs have been developed, and, when used appropriately, most of them have demonstrated beneficial effects in the liver in a variety of pathological settings. In this review, we discuss the relationship between NO and hepatotoxicity, and the beneficial effects of NO donors on the liver, using the liver-selective NO donor, V-PYRRO/NO, as an example to demonstrate that pharmacologically delivered NO could have therapeutic benefits for liver disorders. JF - Toxicology AU - Liu, J AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at NIEHS, Mail Drop F0-09, Research Triangle Park, NC 27709, USA, liu6@niehs.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 289 EP - 297 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 208 IS - 2 SN - 0300-483X, 0300-483X KW - Toxicology Abstracts KW - Nitric-oxide synthase KW - Liver diseases KW - Toxicants KW - prodrugs KW - Reviews KW - Nitric oxide KW - Defense mechanisms KW - Metabolism KW - hepatotoxicity KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17766027?accountid=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=Nitric+oxide+and+chemically+induced+hepatotoxicity%3A+beneficial+effects+of+the+liver-selective+nitric+oxide+donor%2C+V-PYRRO%2FNO&rft.au=Liu%2C+J%3BWaalkes%2C+M+P&rft.aulast=Liu&rft.aufirst=J&rft.date=2005-03-01&rft.volume=208&rft.issue=2&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2Fj.tox.2004.11.017 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Nitric oxide; Nitric-oxide synthase; hepatotoxicity; prodrugs; Liver diseases; Toxicants; Metabolism; Defense mechanisms DO - http://dx.doi.org/10.1016/j.tox.2004.11.017 ER - TY - JOUR T1 - Comparison of phenethyl and 6-phenylhexyl isothiocyanate-induced toxicity in rat esophageal cell lines with and without glutathione depletion AN - 17762273; 6138248 AB - Phenethyl isothiocyanate (PEITC) and its synthetic homolog, 6-phenylhexyl isothiocyanate (PHITC), are both potent inhibitors of 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone (NNK)-induced lung mice tumorigenesis. However, unlike PEITC, PHITC enhanced N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. These findings imply that due to its unique chemical properties, PHITC's effects on esophageal cells are procarcinogenic rather than chemopreventive. Relative to PEITC, PHITC is more lipophilic and less reactive, which could result in higher PHITC intracellular levels. Due to ITCs' inherently high level of thiol reactivity, increased intracellular levels of PHITC have the potential to deplete intracellular glutathione (GSH) reserves. Since GSH is a primary intracellular antioxidant and cytoprotective enzyme cofactor, preservation of intracellular GSH status is crucial for cytoprotection. Despite the recognized importance of isothiocyanate structure with the potential for toxicity, no studies have yet investigated the association between the primary intracellular free thiol, GSH, and isothiocyanate-induced toxicity in this target cell population. The present study investigated whether PEITC and PHITC display unique cytotoxic profiles in cultured rat esophageal cells, and also monitored the effects of ITC challenge on cellular GSH status. A final series of experiments investigated the converse i.e. affects of modulation of intracellular GSH status on ITC-mediated toxicity. Dose-response curves revealed that PEITC was significantly more toxic in tumorigenic and non-tumorigenic cells relative to PHITC. The ITC-GSH interaction studies demonstrated comparable GSH levels following either PEITC or PHITC challenge, and also showed that GSH depletion did not augment ITC-mediated cellular toxicity. While our data demonstrate structure related differences in ITC-mediated cytotoxicities, these differences do not appear to be directly attributable to cellular GSH pools. JF - Toxicology Letters AU - Hudson, T S AU - Stoner, G D AU - Morse, MA AU - Young, H AU - Mallery AD - Division of Cancer Prevention, Cancer Prevention Fellowship Program, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA, mallery.1@osu.edu Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 427 EP - 436 PB - Elsevier Science Ireland Ltd., Elsevier House, Brookvale Plaza East Park Shannon, Co. Clare Ireland, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 155 IS - 3 SN - 0378-4274, 0378-4274 KW - Toxicology Abstracts KW - PEITC KW - PHITC KW - GSH KW - Cytotoxicity KW - BSO, buthionine sulfoximine KW - CHX, 2-cyclohexene-1-one KW - DDT, dichlorodiphenyltrichloroethane KW - GSH, glutathione KW - ITCs, isothiocyanates KW - MTT, [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] KW - NMBA, N-nitrosomethylbenzylamine KW - NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone KW - PEITC, phenethyl isothiocyanate KW - PHITC, 6-phenylhexyl isothiocyanate KW - Antioxidants KW - Glutathione KW - Tumorigenesis KW - Intracellular levels KW - Toxicity KW - Lipophilic KW - Cofactors KW - phenethyl isothiocyanate KW - Lung KW - Thiols KW - Preservation KW - N-Nitrosomethylbenzylamine KW - isothiocyanate KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17762273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Comparison+of+phenethyl+and+6-phenylhexyl+isothiocyanate-induced+toxicity+in+rat+esophageal+cell+lines+with+and+without+glutathione+depletion&rft.au=Hudson%2C+T+S%3BStoner%2C+G+D%3BMorse%2C+MA%3BYoung%2C+H%3BMallery&rft.aulast=Hudson&rft.aufirst=T&rft.date=2005-03-01&rft.volume=155&rft.issue=3&rft.spage=427&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/10.1016%2Fj.toxlet.2004.11.012 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Antioxidants; Glutathione; Tumorigenesis; Intracellular levels; Toxicity; Lipophilic; Cytotoxicity; Cofactors; phenethyl isothiocyanate; Lung; Thiols; Preservation; N-Nitrosomethylbenzylamine; isothiocyanate DO - http://dx.doi.org/10.1016/j.toxlet.2004.11.012 ER - TY - JOUR T1 - Image informatics at a national research center AN - 17524411; 6201669 AB - Image informatics at the Communications Engineering Branch of the Lister Hill National Center for Biomedical Communications (LHNCBC), an R&D division of the National Library of Medicine (NLM), includes document and biomedical images. In both domains, research into computer-assisted methods for information extraction, and the implementation of prototype systems incorporating such methods, is central to our mission. Current document image research focuses on extracting bibliographic data from scanned journal articles. Current biomedical imaging work focuses on content-based image retrieval (CBIR) and related problems in segmentation, indexing, and classifying collections of images of the spine and of the uterine cervix. JF - Computerized Medical Imaging and Graphics AU - Long, L R AU - Antani, S K AU - Thoma, G R AD - Department of Health and Human Services, Communications Engineering Branch, US National Library of Medicine, Lister Hill National Center for Biomedical Communications, National Institutes of Health, 8600 Rockville Pike, Bldg 38A MS 55, Bethesda, MD 20894, USA, rlong@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 171 EP - 193 PB - Pergamon Press Inc., 660 White Plains Rd., Floor 2 Tarrytown NY 10591-5153 USA VL - 29 IS - 2-3 SN - 0895-6111, 0895-6111 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Uterus KW - Spine KW - Segmentation KW - Bioinformatics KW - Cervix KW - imaging KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17524411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Computerized+Medical+Imaging+and+Graphics&rft.atitle=Image+informatics+at+a+national+research+center&rft.au=Long%2C+L+R%3BAntani%2C+S+K%3BThoma%2C+G+R&rft.aulast=Long&rft.aufirst=L&rft.date=2005-03-01&rft.volume=29&rft.issue=2-3&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Computerized+Medical+Imaging+and+Graphics&rft.issn=08956111&rft_id=info:doi/10.1016%2Fj.compmedimag.2004.09.015 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cervix; Segmentation; Spine; imaging; Uterus; Bioinformatics DO - http://dx.doi.org/10.1016/j.compmedimag.2004.09.015 ER - TY - JOUR T1 - BM stem cells and cardiac repair: where do we stand in 2004? AN - 17468694; 6654769 AB - Adult BM stem cells are being investigated for their potential to regenerate injured tissues by a process referred to as plasticity or transdifferentiation. Although data supporting stem cell plasticity is extensive, a controversy has emerged based on findings that propose cell-cell fusion as a more appropriate interpretation for this phenomenon. A major focus of this controversy is the claim that acutely infarcted myocardium in adult hearts can be regenerated by BM stem cells. Many researchers consider the adult heart to be a post-mitotic organ, whereas others believe that a low level of cardiomyocyte renewal occurs throughout life. If renewal occurs, it may be in response to cardiac stem cell activity or to stem cells that migrate from distant tissues. Post-mortem microscopic analysis of experimentally induced myocardial infarctions in several rodent models suggests that cardiomyocyte renewal is achieved by stem cells that infiltrate the damaged tissue. For a better understanding of the possible involvement of stem cells in myocardial regeneration, it is important to develop appropriate technologies to monitor myocardial repair over time with an emphasis on large animal models. Studies on non-human primate, swine and canine models of acute myocardial infarctions would enable investigators to utilize clinical quality cell-delivery devices, track labeled donor cells after precision transplantation and utilize non-invasive imaging for functional assays over time with clinical accuracy. In addition, if stem cell plasticity is to reach the next level of acceptance, it is important to identify the environmental cues needed for stem cell trafficking and to define the genetic and cellular mechanisms that initiate transdifferentiation. Only then will it be possible to determine if, and to what extent, BM stem cells are involved in myocardial regeneration and to begin to regulate precisely tissue repair. JF - Cytotherapy AU - Orlic, D AD - Cardiovascular Branch National Heart Lung and Blood Institute, NIH Bethesda Maryland USA Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 3 EP - 15 VL - 7 IS - 1 SN - 1465-3249, 1465-3249 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Heart KW - Donors KW - Stem cells KW - Animal models KW - cardiomyocytes KW - imaging KW - Cell fusion KW - Myocardial infarction KW - Myocardium KW - Plasticity (functional) KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17468694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotherapy&rft.atitle=BM+stem+cells+and+cardiac+repair%3A+where+do+we+stand+in+2004%3F&rft.au=Orlic%2C+D&rft.aulast=Orlic&rft.aufirst=D&rft.date=2005-03-01&rft.volume=7&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/10.1080%2F14653240510018028 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Stem cells; Heart; Animal models; Myocardial infarction; cardiomyocytes; imaging; Cell fusion; Plasticity (functional); Donors; Myocardium DO - http://dx.doi.org/10.1080/14653240510018028 ER - TY - JOUR T1 - Executive Function Correlates with Walking Speed in Older Persons: The InCHIANTI Study AN - 17346681; 6238259 AB - Objectives: To study the association between performance on psychological tests of executive function and performance on lower extremity tasks with different attentional demands in a large sample of nondemented, older adults. Design: Cross-sectional study. Setting: Community-based. Participants: Nine hundred twenty-six persons aged 65 and older, without dementia, stroke, parkinsonism, visual impairment, or current treatment with neuroleptics, enrolled in a large epidemiological study. Measurements: Trail Making Test (TMT) parts A and B and two performance-based measures of lower extremity function that require different executive-attentional-demanding skills: walking speed on a 4-m course at usual pace and walking speed on a 7-m obstacle course at fast pace. A difference score (Delta TMT), obtained by subtracting time to perform part A from time to perform part B of the TMT, was used as an indicator of executive function. Based on Delta TMT, subjects were divided into poor performance, intermediate performance, and good performance. Results: After adjustment, no association between Delta TMT and 4-m course usual-pace walking speed was found. Participants with poor Delta TMT and with intermediate Delta TMT performance were more likely to be in the lowest tertile for 7-m obstacle course walking speed. Conclusion: In nondemented older persons, executive function is independently associated with tasks of lower extremity function that require high attentional demand. JF - Journal of the American Geriatrics Society AU - Ble, Alesandro AU - Volpato, Stefano AU - Zuliani, Giovanni AU - Guralnik, Jack M AU - Bandinelli, Stefania AU - Lauretani, Fulvio AU - Bartali, Benedetta AU - Maraldi, Cinzia AU - Fellin, Renato AU - Ferrucci, Luigi AD - Luigi Ferrucci, MD, PhD, National Institutes of Heath, National Institute on Aging, Harbor Hospital, 3001 S. Hanover Street, Baltimore, MD 21225, ferruccilu@grc.nia.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 410 EP - 415 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 53 IS - 3 SN - 0002-8614, 0002-8614 KW - Physical Education Index KW - PE 100:Kinesiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17346681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Geriatrics+Society&rft.atitle=Executive+Function+Correlates+with+Walking+Speed+in+Older+Persons%3A+The+InCHIANTI+Study&rft.au=Ble%2C+Alesandro%3BVolpato%2C+Stefano%3BZuliani%2C+Giovanni%3BGuralnik%2C+Jack+M%3BBandinelli%2C+Stefania%3BLauretani%2C+Fulvio%3BBartali%2C+Benedetta%3BMaraldi%2C+Cinzia%3BFellin%2C+Renato%3BFerrucci%2C+Luigi&rft.aulast=Ble&rft.aufirst=Alesandro&rft.date=2005-03-01&rft.volume=53&rft.issue=3&rft.spage=410&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Geriatrics+Society&rft.issn=00028614&rft_id=info:doi/10.1111%2Fj.1532-5415.2005.53157.x LA - English DB - Physical Education Index N1 - Date revised - 2006-12-01 N1 - SuppNotes - Figures, 1; tables, 2; references, 30. N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1111/j.1532-5415.2005.53157.x ER - TY - JOUR T1 - Global Gene Expression Associated with Hepatocarcinogenesis in Adult Male Mice Induced by in Utero Arsenic Exposure AN - 17230733; 6963734 AB - Our previous work has shown that exposure to inorganic arsenic in utero produces hepatocellular carcinoma (HCC) in adult male mice. To explore further the molecular mechanisms of transplacental arsenic hepatocarcinogenesis, we conducted a second arsenic transplacental carcinogenesis study and used a genomewide microarray to profile arsenic-induced aberrant gene expression more extensively. Briefly, pregnant C3H mice were given drinking water containing 85 ppm arsenic as sodium arsenite or unaltered water from days 8 to 18 of gestation. The incidence of HCC in adult male offspring was increased 4-fold and tumor multiplicity 3-fold after transplacental arsenic exposure. Samples of normal liver and liver tumors were taken at autopsy for genomic analysis. Arsenic exposure in utero resulted in significant alterations (p 90% concordance. Arsenic-altered gene expression included activation of oncogenes and HCC biomarkers, and increased expression of cell proliferation-related genes, stress proteins, and insulin-like growth factors and genes involved in cell-cell communications. Liver feminization was evidenced by increased expression of estrogen-linked genes and altered expression of genes that encode gender-related metabolic enzymes. These novel findings are in agreement with the biology and histology of arsenic-induced HCC, thereby indicating that multiple genetic events are associated with transplacental arsenic hepatocarcinogenesis. JF - Environmental Health Perspectives AU - Liu, Jie AU - Xie, Yaxiong AU - Ducharme, DMK AU - Shen, Jun AU - Diwan, BA AU - Merrick, BA AU - Grissom, S F AU - Tucker, C J AU - Paules, R S AU - Tennant, R AU - Waalkes, M P AD - Inorganic Carcinogenesis Section, NCI at NIEHS, Mail Drop F0-09, Research Triangle Park, NC 27709, USA, waalkes@niehs.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 404 EP - 411 VL - 114 IS - 3 SN - 0091-6765, 0091-6765 KW - Genetics Abstracts; Toxicology Abstracts KW - Autopsy KW - Molecular modelling KW - DNA microarrays KW - Gene expression KW - Myc protein KW - Oncogenes KW - Gestation KW - Polymerase chain reaction KW - Intercellular signalling KW - Hepatocellular carcinoma KW - Western blotting KW - Arsenic KW - Sodium arsenite KW - stress proteins KW - Enzymes KW - Tumors KW - Intrauterine exposure KW - biomarkers KW - Transplacental carcinogenesis KW - Pregnancy KW - Insulin-like growth factors KW - Genomic analysis KW - Progeny KW - Drinking water KW - X 24165:Biochemistry KW - G 07730:Development & Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17230733?accountid=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=Global+Gene+Expression+Associated+with+Hepatocarcinogenesis+in+Adult+Male+Mice+Induced+by+in+Utero+Arsenic+Exposure&rft.au=Liu%2C+Jie%3BXie%2C+Yaxiong%3BDucharme%2C+DMK%3BShen%2C+Jun%3BDiwan%2C+BA%3BMerrick%2C+BA%3BGrissom%2C+S+F%3BTucker%2C+C+J%3BPaules%2C+R+S%3BTennant%2C+R%3BWaalkes%2C+M+P&rft.aulast=Liu&rft.aufirst=Jie&rft.date=2005-03-01&rft.volume=114&rft.issue=3&rft.spage=404&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Fehp.8534 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Molecular modelling; Autopsy; Western blotting; Arsenic; Sodium arsenite; stress proteins; Enzymes; Intrauterine exposure; Tumors; biomarkers; DNA microarrays; Transplacental carcinogenesis; Pregnancy; Myc protein; Gene expression; Oncogenes; Genomic analysis; Gestation; Insulin-like growth factors; Polymerase chain reaction; Progeny; Drinking water; Intercellular signalling; Hepatocellular carcinoma DO - http://dx.doi.org/10.1289/ehp.8534 ER - TY - JOUR T1 - Exercise treadmill testing using a modified exercise protocol in women with suspected myocardial ischemia: Findings from the National Heart, Lung and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) AN - 1504432186; 15864243 AB - Background Exercise testing, a major diagnostic modality in individuals with suspected coronary artery disease (CAD), has in general demonstrated less overall diagnostic accuracy in women compared to men. As part of the WISE, a modified protocol was examined with the intention of improving reliability of exercise testing. Methods Criteria for entry in the WISE study include clinically indicated coronary angiography. Exercise testing was performed using a protocol modified to be more appropriate for women. The study population consisted of 96 women, mean age of 55.8 y (range 34-77), who completed exercise treadmill test (ETT). Most (78%) were postmenopausal; 96% had ?2 risk factors for CAD. Results By core laboratory angiography, 29/96 women had stenosis ?50% in at least one coronary artery. Of these 29 women, 9 had abnormal ETT, yielding overall sensitivity of 31%. The remaining 20 women had normal (12/29, 41%) or nondiagnostic (8/29, 28%) studies. Among the 67 women with minimal or no coronary stenosis, 35 had no ischemic ST-segment changes during ETT, yielding overall specificity of 52%. Analysis with exclusion of women with nondiagnostic studies yielded sensitivity and specificity of 43% and 66%, respectively. The presence of coronary artery stenosis and inability to perform ETT, but not results of testing, predicted the outcomes of myocardial infarction, heart failure, and death. Conclusions Exercise treadmill test appears to be of limited diagnostic value in women with suspected myocardial ischemia referred for coronary angiography. Sensitivity and specificity remain poor even with modified exercise protocol and core laboratory angiographic analysis. These findings merit consideration in view of current guidelines that recommend exercise testing in women with suspected CAD. (Am Heart J 2005;149:1-7.) JF - The American Heart Journal AU - Lewis, Jannet F AU - McGorray, Susan AU - Lin, Lang AU - Pepine, Carl J AU - Chaitman, Bernard AU - Doyle, Mark AU - Edmundowicz, Daniel AU - Sharaf, Barry L AU - Merz, C Noel Bairey Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 527 EP - 33 CY - Philadelphia PB - Elsevier Limited VL - 149 IS - 3 SN - 00028703 KW - Medical Sciences--Cardiovascular Diseases KW - Exercise KW - Heart attacks KW - Coronary vessels KW - Colleges & universities KW - Statistical methods KW - Cardiovascular disease KW - Ischemia KW - Medical imaging KW - Blood pressure KW - Heart rate KW - Patients KW - Heart failure KW - Diabetes KW - Fitness equipment KW - Myocardial Ischemia -- etiology KW - Humans KW - Electrocardiography KW - Coronary Stenosis -- complications KW - Coronary Angiography KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Sensitivity & Specificity KW - Female KW - Clinical Protocols KW - Exercise Test -- methods KW - Myocardial Ischemia -- diagnosis KW - Women's Health KW - Coronary Stenosis -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1504432186?accountid=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+Heart+Journal&rft.atitle=Exercise+treadmill+testing+using+a+modified+exercise+protocol+in+women+with+suspected+myocardial+ischemia%3A+Findings+from+the+National+Heart%2C+Lung+and+Blood+Institute-sponsored+Women%27s+Ischemia+Syndrome+Evaluation+%28WISE%29&rft.au=Lewis%2C+Jannet+F%3BMcGorray%2C+Susan%3BLin%2C+Lang%3BPepine%2C+Carl+J%3BChaitman%2C+Bernard%3BDoyle%2C+Mark%3BEdmundowicz%2C+Daniel%3BSharaf%2C+Barry+L%3BMerz%2C+C+Noel+Bairey&rft.aulast=Lewis&rft.aufirst=Jannet&rft.date=2005-03-01&rft.volume=149&rft.issue=3&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=The+American+Heart+Journal&rft.issn=00028703&rft_id=info:doi/10.1016%2Fj.ahj.2004.03.068 LA - English DB - ProQuest Central N1 - Copyright - Copyright Elsevier Limited Mar 2005 N1 - Last updated - 2014-04-30 N1 - CODEN - AHJOA2 DO - http://dx.doi.org/10.1016/j.ahj.2004.03.068 ER - TY - JOUR T1 - Mechanisms of resistance to anticancer drugs: the role of the polymorphic ABC transporters ABCB1 and ABCG2 AN - 1020847002; 16781670 AB - ATP-binding cassette (ABC) genes play a role in the resistance of malignant cells to anticancer agents. The ABC gene products, including ABCB1 (P-glycoprotein) and ABCG2 (breast cancer-resistance protein [BCRP], mitoxantrone-resistance protein [MXR], or ABC transporter in placenta [ABCP]), are also known to influence oral absorption and disposition of a wide variety of drugs. As a result, the expression levels of these proteins in humans have important consequences for an individual's susceptibility to certain drug-induced side effects, interactions, and treatment efficacy. Naturally occurring variants in ABC transporter genes have been identified that might affect the function and expression of the protein. This review focuses on recent advances in the pharmacogenetics of the ABC transporters ABCB1 and ABCG2, and discusses potential implications of genetic variants for the chemotherapeutic treatment of cancer. JF - Pharmacogenomics AU - Lepper, Erin R AU - Nooter, Kees AU - Verweij, Jaap AU - Acharya, Milin R AU - Figg, William D AU - Sparreboom, Alex AD - National Cancer Institute, Clinical Pharmacology Research Core, Building 10, Room 5A01, 9000 Rockville Pike, Bethesda, MD 20892, USATel.: +1 (301) 402 9498; Fax: +1 (301) 402 8606; E-mail:, sparreba@mail.nih.gov Y1 - 2005/03// PY - 2005 DA - Mar 2005 SP - 115 EP - 138 PB - Future Science Group (FSG), Unitec House, 2 Albert Place London N3 1QB United Kingdom VL - 6 IS - 2 SN - 1462-2416, 1462-2416 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - ABC transporter KW - G 07720:Immunogenetics KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1020847002?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenomics&rft.atitle=Mechanisms+of+resistance+to+anticancer+drugs%3A+the+role+of+the+polymorphic+ABC+transporters+ABCB1+and+ABCG2&rft.au=Lepper%2C+Erin+R%3BNooter%2C+Kees%3BVerweij%2C+Jaap%3BAcharya%2C+Milin+R%3BFigg%2C+William+D%3BSparreboom%2C+Alex&rft.aulast=Lepper&rft.aufirst=Erin&rft.date=2005-03-01&rft.volume=6&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Pharmacogenomics&rft.issn=14622416&rft_id=info:doi/10.1517%2F14622416.6.2.115 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-06-01 N1 - Number of references - 1 N1 - Last updated - 2014-03-10 N1 - SubjectsTermNotLitGenreText - ABC transporter DO - http://dx.doi.org/10.1517/14622416.6.2.115 ER - TY - JOUR T1 - Mitochondria, oxidants, and aging. AN - 67470702; 15734681 AB - The free radical theory of aging postulates that the production of intracellular reactive oxygen species is the major determinant of life span. Numerous cell culture, invertebrate, and mammalian models exist that lend support to this half-century-old hypothesis. Here we review the evidence that both supports and conflicts with the free radical theory and examine the growing link between mitochondrial metabolism, oxidant formation, and the biology of aging. JF - Cell AU - Balaban, Robert S AU - Nemoto, Shino AU - Finkel, Toren AD - Laboratory of Cardiac Energetics, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2005/02/25/ PY - 2005 DA - 2005 Feb 25 SP - 483 EP - 495 VL - 120 IS - 4 SN - 0092-8674, 0092-8674 KW - Free Radicals KW - 0 KW - Oxidants KW - Reactive Oxygen Species KW - Index Medicus KW - Yeasts KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Mutation -- physiology KW - Mutation -- genetics KW - Nutritional Physiological Phenomena -- physiology KW - Aging -- physiology KW - Mitochondria -- metabolism KW - Oxidants -- metabolism KW - Free Radicals -- metabolism KW - Mitochondria -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67470702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mitochondria%2C+oxidants%2C+and+aging.&rft.au=Balaban%2C+Robert+S%3BNemoto%2C+Shino%3BFinkel%2C+Toren&rft.aulast=Balaban&rft.aufirst=Robert&rft.date=2005-02-25&rft.volume=120&rft.issue=4&rft.spage=483&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-14 N1 - Date created - 2005-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chromatin-dependent E1A activity modulates NF-kappaB RelA-mediated repression of glucocorticoid receptor-dependent transcription. AN - 67446227; 15556937 AB - The role of chromatin-dependent regulatory mechanisms in the repression of glucocorticoid-dependent transcription from the murine mammary tumor virus (MMTV) promoter by p65 and E1A was investigated by using chromatin and transiently transfected reporters. The p65 RelA subunit of NF-kappaB represses MMTV expression on either transient or integrated reporters. In contrast, the viral oncoprotein E1A represses a transient but not an integrated MMTV. E1A repression is attenuated by chromatin, suggesting p65 but not E1A manipulates chromatin appropriately to inhibit the GR. Coexpression of p65 and E1A additively represses the transient MMTV but restores the transcriptional activation of the chromatin MMTV in response to glucocorticoids. This indicates that E1A has a dominant chromatin-dependent activity that attenuates repression by p65. E1A, p65, and GR bind the MMTV promoter, and chromatin remodeling enhances binding on both repressed and activated promoters. In addition, p65 requires Brg for repression of the integrated MMTV. This suggests that neither p65 repression nor E1A attenuation of repression results from an inhibition of remodeling that prevents transcription factor binding. Furthermore, p300/CBP is also required for both repression and attenuation by p65 and E1A. E1A and p65 mutants that do not bind p300/CBP are inactive, indicative of a requirement for p300/CBP-dependent complex formation for both repression and attenuation with chromatin. These data suggest that both the p65-dependent repression and the E1A-mediated attenuation of repression require the Brg1-dependent chromatin remodeling function and p300/CBP-dependent complex formation at a promoter assembled within chromatin. JF - The Journal of biological chemistry AU - Burkhart, Barbara A AU - Hebbar, Pratibha B AU - Trotter, Kevin W AU - Archer, Trevor K AD - Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2005/02/25/ PY - 2005 DA - 2005 Feb 25 SP - 6349 EP - 6358 VL - 280 IS - 8 SN - 0021-9258, 0021-9258 KW - Chromatin KW - 0 KW - FGF3 protein, human KW - Fibroblast Growth Factor 3 KW - NF-kappa B KW - Nuclear Proteins KW - Receptors, Glucocorticoid KW - Repressor Proteins KW - Trans-Activators KW - Transcription Factor RelA KW - Transcription Factors KW - Fibroblast Growth Factors KW - 62031-54-3 KW - SMARCA4 protein, human KW - EC 3.6.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Transcription Factors -- physiology KW - Promoter Regions, Genetic KW - Humans KW - Chromatin Assembly and Disassembly KW - Fibroblast Growth Factors -- genetics KW - Cell Line KW - Repressor Proteins -- physiology KW - Chromatin -- physiology KW - Transcription, Genetic KW - Gene Expression Regulation KW - Trans-Activators -- physiology KW - NF-kappa B -- physiology KW - Receptors, Glucocorticoid -- physiology KW - Nuclear Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67446227?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Chromatin-dependent+E1A+activity+modulates+NF-kappaB+RelA-mediated+repression+of+glucocorticoid+receptor-dependent+transcription.&rft.au=Burkhart%2C+Barbara+A%3BHebbar%2C+Pratibha+B%3BTrotter%2C+Kevin+W%3BArcher%2C+Trevor+K&rft.aulast=Burkhart&rft.aufirst=Barbara&rft.date=2005-02-25&rft.volume=280&rft.issue=8&rft.spage=6349&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 - 2005-04-08 N1 - Date created - 2005-02-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel Anticholinesterases Based on the Molecular Skeletons of Furobenzofuran and Methanobenzodioxepinev AN - 19384201; 7149661 AB - Reductive cyclization of 5-hydroxy-3-methyl-3-methoxycarbonylmethylenebenzofuran-2(3H)-one (4) gave 5-hydroxy-3a-methyl-2,3,3a,8a-tatrahydrofiiro[2,3-b]benzofuran (5) and the rearrangement product 7-hydroxy-4,5-dihydro-2,5-methano-1,3-benzodioxepine (6). Reaction of compounds 5 and 6 with different isocyanates provided two series novel carbamates (7-12) whose structures were confirmed by X-ray crystallography. These were assessed for anticholinesterase action against freshly prepared human enzyme and proved to be potent inhibitors of either acetyl-(AChE) or butyrylcholinesterase (BChE) with specific compounds exhibiting remarkable selectivity. Because the two series of carbamates (7-12) differ in their phenolic moieties, their respective potency and selectivity for AChE versus BChE was governed by their N-substituted groups. This same characteristic was also present in a series of physovenine analogues (1,13,15,17) and physostigmine analogues (2, 14, 16, 18). These structure-activity relations proved valuable in elucidating the mechanisms underpinning the interaction between carbamate-based cholinesterase inhibitors and their enzyme target. In addition, because physostigmine analogues have demonstrated activity in lowering the Alzheimer's disease protein, amyloid precursor protein (APP), examples of the two new series of carbamates were characterized in culture assays of quantifying cell viability and synthesis of APP. JF - Journal of Medicinal Chemistry AU - Luo, W AU - Yu, Q-S AU - Zhan, M AU - Parrish, D AU - Deschamps, J R AU - Kulkarni, S S AU - Holloway, H W AU - Alley, G M AU - Lahiri, D K AU - Brossi, A AU - Greig, N H AD - Drug Design & Development Section, Laboratory of Neurosciences, and Bioinformatics Unit, Research Resources Branch, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA Y1 - 2005/02/24/ PY - 2005 DA - 2005 Feb 24 SP - 986 EP - 994 VL - 48 IS - 4 SN - 0022-2623, 0022-2623 KW - Biotechnology and Bioengineering Abstracts KW - X-ray crystallography KW - Neurodegenerative diseases KW - Alzheimer's disease KW - phenolic compounds KW - Enzymes KW - Cell culture KW - Physostigmine KW - Cholinesterase KW - isocyanates KW - Amyloid precursor protein KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19384201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Medicinal+Chemistry&rft.atitle=Novel+Anticholinesterases+Based+on+the+Molecular+Skeletons+of+Furobenzofuran+and+Methanobenzodioxepinev&rft.au=Luo%2C+W%3BYu%2C+Q-S%3BZhan%2C+M%3BParrish%2C+D%3BDeschamps%2C+J+R%3BKulkarni%2C+S+S%3BHolloway%2C+H+W%3BAlley%2C+G+M%3BLahiri%2C+D+K%3BBrossi%2C+A%3BGreig%2C+N+H&rft.aulast=Luo&rft.aufirst=W&rft.date=2005-02-24&rft.volume=48&rft.issue=4&rft.spage=986&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medicinal+Chemistry&rft.issn=00222623&rft_id=info:doi/10.1021%2Fjm049309%2B LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Alzheimer's disease; Amyloid precursor protein; Physostigmine; Enzymes; X-ray crystallography; Cholinesterase; isocyanates; Cell culture; Neurodegenerative diseases; phenolic compounds DO - http://dx.doi.org/10.1021/jm049309+ ER - TY - JOUR T1 - Identification of a dopamine transporter ligand that blocks the stimulant effects of cocaine. AN - 67454773; 15728828 AB - There is a large unmet medical need for cocaine addiction treatments. Studies have indicated that the dopamine transporter (DAT) is the primary biological target of cocaine, and most drugs that have DAT affinity have behavioral effects like those of cocaine. However, analogs of benztropine have high DAT affinity and behavioral effects that show varying degrees of similarity to cocaine. We now report the discovery that a benztropine analog, JHW007, with high affinity for the DAT does not have cocaine-like behavioral effects and antagonizes the effects of cocaine. JHW007 occupied the DAT in vivo more slowly than did cocaine and had not reached an apparent plateau up to 270 min after injection. The in vivo binding of cocaine to the DAT suggested rate of DAT occupancy as an important contributor to its behavioral effects, and the slow association with the DAT may provide an explanation for JHW007 being relatively devoid of cocaine-like behavioral effects. The antagonism of cocaine suggests that DAT ligands with reduced cocaine-like activity can function as cocaine antagonists and suggests JHW007 as a lead for discovery of cocaine-abuse pharmacotherapeutics. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Desai, Rajeev I AU - Kopajtic, Theresa A AU - Koffarnus, Mikhail AU - Newman, Amy Hauck AU - Katz, Jonathan L AD - Psychobiology, Medications Discovery Research Branch, National Institute on Drug Abuse, Intramural Research Program, Department of Health and Human Services, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2005/02/23/ PY - 2005 DA - 2005 Feb 23 SP - 1889 EP - 1893 VL - 25 IS - 8 KW - Central Nervous System Stimulants KW - 0 KW - Dopamine Antagonists KW - Dopamine Plasma Membrane Transport Proteins KW - Ligands KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - N-(n-butyl)-(bis-fluorophenyl)methoxytropane KW - N-allyl-(bisfluorophenyl)methoxytropane KW - Nerve Tissue Proteins KW - Slc6a3 protein, mouse KW - Slc6a3 protein, rat KW - RTI 121 KW - 146145-21-3 KW - Benztropine KW - 1NHL2J4X8K KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Corpus Striatum -- metabolism KW - Dopamine Antagonists -- pharmacology KW - Mice KW - Cerebellum -- metabolism KW - Rats KW - Cerebellum -- drug effects KW - Corpus Striatum -- drug effects KW - Motor Activity -- drug effects KW - Inhibitory Concentration 50 KW - Male KW - Nerve Tissue Proteins -- drug effects KW - Membrane Glycoproteins -- drug effects KW - Cocaine -- analogs & derivatives KW - Benztropine -- analogs & derivatives KW - Membrane Transport Proteins -- drug effects KW - Central Nervous System Stimulants -- antagonists & inhibitors KW - Benztropine -- pharmacology KW - Cocaine -- pharmacology KW - Cocaine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67454773?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Identification+of+a+dopamine+transporter+ligand+that+blocks+the+stimulant+effects+of+cocaine.&rft.au=Desai%2C+Rajeev+I%3BKopajtic%2C+Theresa+A%3BKoffarnus%2C+Mikhail%3BNewman%2C+Amy+Hauck%3BKatz%2C+Jonathan+L&rft.aulast=Desai&rft.aufirst=Rajeev&rft.date=2005-02-23&rft.volume=25&rft.issue=8&rft.spage=1889&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 - 2005-10-26 N1 - Date created - 2005-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Solutes probe hydration in specific association of cyclodextrin and adamantane. AN - 67436324; 15713096 AB - Using microcalorimetry, we follow changes in the association free energy of beta-cyclodextrin (CD) with the hydrophobic part of adamantane carboxylate (AD) due to added salt or polar (net-neutral) solutes that are excluded from the molecular interacting surfaces. Changes in binding constants with solution osmotic pressure (water activity) translate into changes in the preferential hydration upon complex formation. We find that these changes correspond to a release of 15-25 solute-excluding waters upon CD/AD association. Reflecting the preferential interaction of solute with reactants versus products, we find that changes in hydration depend on the type of solute used. All solutes used here result in a large change in the enthalpy of the CD-AD binding reaction. In one class of solutes, the corresponding entropy change is much smaller, while in the other class, the entropy change almost fully compensates the solute-specific enthalpy. For many of the solutes, the number of waters released correlates well with their effect on air-water surface tensions. We corroborate these results using vapor pressure osmometry to probe individually the hydration of reactants and products of association, and we discuss the possible interactions and forces between cosolute and hydrophobic surfaces responsible for different kinds of solute exclusion. JF - Journal of the American Chemical Society AU - Harries, Daniel AU - Rau, Donald C AU - Parsegian, V Adrian AD - Laboratory of Physical and Structural Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-0924, USA. harries@helix.nih.gov Y1 - 2005/02/23/ PY - 2005 DA - 2005 Feb 23 SP - 2184 EP - 2190 VL - 127 IS - 7 SN - 0002-7863, 0002-7863 KW - beta-Cyclodextrins KW - 0 KW - Water KW - 059QF0KO0R KW - adamantanecarboxylic acid KW - 828-51-3 KW - betadex KW - JV039JZZ3A KW - Adamantane KW - PJY633525U KW - Index Medicus KW - Calorimetry -- methods KW - Osmotic Pressure KW - Thermodynamics KW - Water -- chemistry KW - Adamantane -- chemistry KW - beta-Cyclodextrins -- chemistry KW - Adamantane -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67436324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Chemical+Society&rft.atitle=Solutes+probe+hydration+in+specific+association+of+cyclodextrin+and+adamantane.&rft.au=Harries%2C+Daniel%3BRau%2C+Donald+C%3BParsegian%2C+V+Adrian&rft.aulast=Harries&rft.aufirst=Daniel&rft.date=2005-02-23&rft.volume=127&rft.issue=7&rft.spage=2184&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Chemical+Society&rft.issn=00027863&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-18 N1 - Date created - 2005-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cardiovascular risk factors and migraine: the GEM population-based study. AN - 67459160; 15728281 AB - Migraine, particularly with aura, is a risk factor for early-onset ischemic stroke. The underlying mechanisms are unknown, but may in part be due to migraineurs having an increased risk profile for cardiovascular disease. In this study, the authors compare the cardiovascular risk profile of adult migraineurs to that of nonmigraineurs. Participants (n = 5,755, 48% men, age 20 to 65 years) are from the Genetic Epidemiology of Migraine (GEM) study, a population-based study in the Netherlands. A total of 620 current migraineurs were identified: 31% with aura (MA), 64% without aura (MO), and 5% unclassified. Controls were 5,135 individuals without lifetime migraine. Measured cardiovascular risk factors included blood pressure (BP), serum total and high-density lipoprotein cholesterol (TC, HDL), smoking, oral contraceptive use, and the Framingham risk score for myocardial infarction or coronary heart disease (CHD) death. Compared to controls, migraineurs were more likely to smoke (OR = 1.43 [1.1 to 1.8]), less likely to consume alcohol (OR = 0.58 [0.5 to 0.7]), and more likely to report a parental history of early myocardial infarction. Migraineurs with aura were more likely to have an unfavorable cholesterol profile (TC > or = 240 mg/dL [OR = 1.43 (0.97 to 2.1)], TC:HDL ratio > 5.0 [OR = 1.64 (1.1 to 2.4)]), have elevated BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg [OR = 1.76 (1.04 to 3.0)]), and report a history of early onset CHD or stroke (OR = 3.96 [1.1 to 14.3]); female migraineurs with aura were more likely to be using oral contraceptives (OR = 2.06 [1.05 to 4.0]). The odds of having an elevated Framingham risk score for CHD were approximately doubled for the migraineurs with aura. Migraineurs, particularly with aura, have a higher cardiovascular risk profile than individuals without migraine. JF - Neurology AU - Scher, A I AU - Terwindt, G M AU - Picavet, H S J AU - Verschuren, W M M AU - Ferrari, M D AU - Launer, L J AD - Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. ascher@usuhs.mil Y1 - 2005/02/22/ PY - 2005 DA - 2005 Feb 22 SP - 614 EP - 620 VL - 64 IS - 4 KW - Contraceptives, Oral, Hormonal KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Netherlands -- epidemiology KW - Pregnancy Complications, Cardiovascular -- epidemiology KW - Myocardial Infarction -- genetics KW - Humans KW - Aged KW - Contraceptives, Oral, Hormonal -- adverse effects KW - Alcohol Drinking -- epidemiology KW - Smoking -- epidemiology KW - Pregnancy KW - Stroke -- epidemiology KW - Migraine without Aura -- epidemiology KW - Cross-Sectional Studies KW - Migraine with Aura -- epidemiology KW - Social Class KW - Risk Factors KW - Hypertension -- epidemiology KW - Adult KW - Middle Aged KW - Female KW - Male KW - Hypercholesterolemia -- epidemiology KW - Migraine Disorders -- epidemiology KW - Cardiovascular Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67459160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cardiovascular+risk+factors+and+migraine%3A+the+GEM+population-based+study.&rft.au=Scher%2C+A+I%3BTerwindt%2C+G+M%3BPicavet%2C+H+S+J%3BVerschuren%2C+W+M+M%3BFerrari%2C+M+D%3BLauner%2C+L+J&rft.aulast=Scher&rft.aufirst=A&rft.date=2005-02-22&rft.volume=64&rft.issue=4&rft.spage=614&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 - 2005-10-18 N1 - Date created - 2005-02-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Neurology. 2005 Nov 22;65(10):1683; author reply 1683 [16301516] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Agonist-induced conformational changes in thyrotropin-releasing hormone receptor type I: disulfide cross-linking and molecular modeling approaches. AN - 67429357; 15709754 AB - The conformational changes at the cytoplasmic ends of transmembrane helices 5 and 6 (TMH5 and TMH6) of thyrotropin-releasing hormone (TRH) receptor type I (TRH-R1) during activation were analyzed by cysteine-scanning mutagenesis followed by disulfide cross-linking and molecular modeling. Sixteen double cysteine mutants were constructed by substitution of one residue at the cytoplasmic end of TMH5 and the other at that of TMH6. The cross-linking experiments indicate that four mutants, Q263C/G212C, Q263C/Y211C, T265C/G212C, and T265C/Y211C, exhibited disulfide bond formation that was sensitive to TRH occupancy. We refined our previous TRH-R1 models by embedding them into a hydrated explicit lipid bilayer. Molecular dynamics simulations of the models, as well as in silico double cysteine models, generated trajectories that were in agreement with experimental results. Our findings suggest that TRH binding induces a separation of the cytoplasmic ends of TMH5 and TMH6 and a rotation of TMH6. These changes likely increase the surface accessible area at the juxtamembrane region of intracellular loop 3 that could promote interactions between G proteins and key residues within the receptor. JF - Biochemistry AU - Huang, Wei AU - Osman, Roman AU - Gershengorn, Marvin C AD - Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 50 South Drive, Building 50/4134, Bethesda, Maryland 20892-1818, USA. Y1 - 2005/02/22/ PY - 2005 DA - 2005 Feb 22 SP - 2419 EP - 2431 VL - 44 IS - 7 SN - 0006-2960, 0006-2960 KW - Cross-Linking Reagents KW - 0 KW - Disulfides KW - Phenanthrolines KW - Receptors, Thyrotropin-Releasing Hormone KW - Thyrotropin-Releasing Hormone KW - 5Y5F15120W KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Computer Simulation KW - Cysteine -- genetics KW - Humans KW - Computational Biology -- methods KW - Amino Acid Sequence KW - Mice KW - Cytoplasm -- chemistry KW - Mutagenesis, Site-Directed KW - Cysteine -- chemistry KW - Phenanthrolines -- chemistry KW - Cytoplasm -- genetics KW - Cytoplasm -- metabolism KW - Molecular Sequence Data KW - Protein Structure, Secondary -- genetics KW - Cell Line KW - Protein Conformation KW - Receptors, Thyrotropin-Releasing Hormone -- chemistry KW - Receptors, Thyrotropin-Releasing Hormone -- agonists KW - Disulfides -- chemistry KW - Cross-Linking Reagents -- chemistry KW - Models, Molecular KW - Thyrotropin-Releasing Hormone -- metabolism KW - Receptors, Thyrotropin-Releasing Hormone -- genetics KW - Thyrotropin-Releasing Hormone -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67429357?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Agonist-induced+conformational+changes+in+thyrotropin-releasing+hormone+receptor+type+I%3A+disulfide+cross-linking+and+molecular+modeling+approaches.&rft.au=Huang%2C+Wei%3BOsman%2C+Roman%3BGershengorn%2C+Marvin+C&rft.aulast=Huang&rft.aufirst=Wei&rft.date=2005-02-22&rft.volume=44&rft.issue=7&rft.spage=2419&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-25 N1 - Date created - 2005-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strategic interactions in multi-institutional epidemics of antibiotic resistance AN - 19818902; 6175319 AB - The increasing frequency of antibiotic resistance in hospital-acquired infections is a major public health concern that has both biological and economic causes. Here we develop conceptual mathematical models that couple the economic incentives and population biology of hospital infection control (HIC). We show that the optimal investment by a hospital for HIC changes with the proportion of patients already colonized with antibiotic-resistant bacteria (ARB) at the time of admission. As that proportion increases, the optimal behavior of a hospital is to increase spending to control ARB with low transmissibility and decrease spending on those with high transmissibility. In some cases, the global optimum investment in HIC can shift discontinuously from one that contains transmission to a do-nothing policy once the proportion already colonized at the time of admission becomes too great. We also show that investments in HIC are determined by a strategic game when several hospitals share patients. Hospitals acting selfishly and rationally will free-ride on the investments of other hospitals, and the level of free-riding should increase with the number of other hospitals in the area. Thus, in areas with many hospitals, the rational strategy for each hospital is to spend less than in areas with few hospitals. Thus, we predict that transmission rates and the prevalence of ARB should be higher in urban hospitals, for instance, compared with rural hospitals. We conclude that regional coordination and planning for HIC is an essential element of public health planning for hospital-acquired infections. JF - Proceedings of the National Academy of Sciences, USA AU - Smith, David L AU - Levin, Simon A AU - Laxminarayan, Ramanan AD - Fogarty International Center, National Institutes of Health, Bethesda, MD Y1 - 2005/02/22/ PY - 2005 DA - 2005 Feb 22 SP - 3153 EP - 3158 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 102 IS - 8 SN - 0027-8424, 0027-8424 KW - Microbiology Abstracts B: Bacteriology KW - Mathematical models KW - Epidemics KW - Economics KW - Infection KW - Antibiotic resistance KW - Hospitals KW - Public health KW - Disease transmission KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19818902?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Strategic+interactions+in+multi-institutional+epidemics+of+antibiotic+resistance&rft.au=Smith%2C+David+L%3BLevin%2C+Simon+A%3BLaxminarayan%2C+Ramanan&rft.aulast=Smith&rft.aufirst=David&rft.date=2005-02-22&rft.volume=102&rft.issue=8&rft.spage=3153&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Epidemics; Mathematical models; Economics; Infection; Antibiotic resistance; Disease transmission; Public health; Hospitals ER - TY - JOUR T1 - Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization AN - 17525180; 6175269 AB - Professional antigen-presenting dendritic cells (DCs) are critical in regulating T cell immune responses at both systemic and mucosal sites. Many Lactobacillus species are normal members of the human gut microflora and most are regarded as safe when administered as probiotics. Because DCs can naturally or therapeutically encounter lactobacilli, we investigated the effects of several well defined strains, representing three species of Lactobacillus on human myeloid DCs (MDCs) and found that they modulated the phenotype and functions of human MDCs. Lactobacillus-exposed MDCs up-regulated HLA-DR, CD83, CD40, CD80, and CD86 and secreted high levels of IL-12 and IL-18, but not IL-10. IL-12 was sustained in MDCs exposed to all three Lactobacillus species in the presence of LPS from Escherichia coli, whereas LPS-induced IL-10 was greatly inhibited. MDCs activated with lactobacilli clearly skewed CD4 super(+) and CD8 super(+) T cells to T helper 1 and Tc1 polarization, as evidenced by secretion of IFN- gamma, but not IL-4 or IL-13. These results emphasize a potentially important role for lactobacilli in modulating immunological functions of DCs and suggest that certain strains could be particularly advantageous as vaccine adjuvants, by promoting DCs to regulate T cell responses toward T helper 1 and Tc1 pathways. JF - Proceedings of the National Academy of Sciences, USA AU - Mohamadzadeh, Mansour AU - Olson, Scott AU - Kalina, Warren V AU - Ruthel, Gordon AU - Demmin, Gretchen L AU - Warfield, Kelly L AU - Bavari, Sina AU - Klaenhammer, Todd R AD - National Cancer Institute, Frederick, MD Y1 - 2005/02/22/ PY - 2005 DA - 2005 Feb 22 SP - 2880 EP - 2885 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 102 IS - 8 SN - 0027-8424, 0027-8424 KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Histocompatibility antigen HLA KW - CD83 antigen KW - CD86 antigen KW - Adjuvants KW - Interleukin 10 KW - Interleukin 12 KW - Dendritic cells KW - Interleukin 13 KW - CD4 antigen KW - Lactobacillus KW - Interleukin 18 KW - Lymphocytes T KW - Escherichia coli KW - Lipopolysaccharides KW - CD80 antigen KW - CD40 antigen KW - g-Interferon KW - probiotics KW - CD8 antigen KW - Polarization KW - Digestive tract KW - ^g-Interferon KW - Vaccines KW - F 06106:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17525180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lactobacilli+activate+human+dendritic+cells+that+skew+T+cells+toward+T+helper+1+polarization&rft.au=Mohamadzadeh%2C+Mansour%3BOlson%2C+Scott%3BKalina%2C+Warren+V%3BRuthel%2C+Gordon%3BDemmin%2C+Gretchen+L%3BWarfield%2C+Kelly+L%3BBavari%2C+Sina%3BKlaenhammer%2C+Todd+R&rft.aulast=Mohamadzadeh&rft.aufirst=Mansour&rft.date=2005-02-22&rft.volume=102&rft.issue=8&rft.spage=2880&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lactobacillus; Escherichia coli; Dendritic cells; Lymphocytes T; Interleukin 12; Interleukin 10; CD4 antigen; CD80 antigen; g-Interferon; probiotics; Digestive tract; Vaccines; Adjuvants; Polarization; ^g-Interferon; CD86 antigen; CD8 antigen; CD40 antigen; Interleukin 18; CD83 antigen; Histocompatibility antigen HLA; Interleukin 13; Lipopolysaccharides ER - TY - JOUR T1 - Identification of the epitope of a monoclonal antibody to DJ-1. AN - 67373498; 15663963 AB - Mutations in DJ-1 can cause early onset parkinsonism. Various antibodies have been generated to detect this protein, one of which is a commonly used monoclonal antibody (clone 3E8). Since results of in situ examinations of DJ-1 expression with this antibody have differed from analyses with species-specific antibodies (e.g. rat), it would be useful to know the epitope for this antibody. Using GFP-tagged deletion constructs of human DJ-1, we have localized the epitope region for this antibody to within residues 56-78 of human DJ-1. Mapping this region to the published three-dimensional structure of DJ-1 indicates that this is a solvent-accessible surface epitope. Immunonegativity of E64D mutant DJ-1 with the monoclonal antibody suggests that glutamate 64 of human DJ-1 contributes to the epitope recognized by this antibody. Moreover, the loss of immunoreactivity due to such a small substitution demonstrates the remarkable sensitivity of the monoclonal antibody 3E8 to DJ-1. JF - Neuroscience letters AU - Miller, David W AU - Wilson, Carmen R AU - Kaleem, Mona A AU - Blackinton, Jeff AU - Cookson, Mark R AD - Laboratory of Neurogenetics, National Institute on Aging, Bldg 35, Rm 1A-1002, 35 Convent Drive, Bethesda, MD 20892, USA. millerda@mail.nih.gov Y1 - 2005/02/21/ PY - 2005 DA - 2005 Feb 21 SP - 203 EP - 206 VL - 374 IS - 3 SN - 0304-3940, 0304-3940 KW - Antibodies, Monoclonal KW - 0 KW - Epitopes KW - Intracellular Signaling Peptides and Proteins KW - Oncogene Proteins KW - PARK7 protein, human KW - EC 3.1.2.- KW - Protein Deglycase DJ-1 KW - Index Medicus KW - Animals KW - Antigen-Antibody Reactions KW - Protein Structure, Secondary KW - Humans KW - Amino Acid Sequence KW - Blotting, Western -- methods KW - Mice KW - Rats KW - Transfection -- methods KW - Mutagenesis, Site-Directed -- immunology KW - Cell Line KW - Antibody Specificity KW - Oncogene Proteins -- immunology KW - Antibodies, Monoclonal -- chemistry KW - Epitopes -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67373498?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+the+epitope+of+a+monoclonal+antibody+to+DJ-1.&rft.au=Miller%2C+David+W%3BWilson%2C+Carmen+R%3BKaleem%2C+Mona+A%3BBlackinton%2C+Jeff%3BCookson%2C+Mark+R&rft.aulast=Miller&rft.aufirst=David&rft.date=2005-02-21&rft.volume=374&rft.issue=3&rft.spage=203&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 - 2005-06-03 N1 - Date created - 2005-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactions of Benzene Oxide with Thiols Including Glutathione AN - 17832570; 6194511 AB - S-Phenylmercapturic acid is a minor metabolite of benzene used as a biomarker for human benzene exposures. The reaction of intracellular glutathione with benzene oxide-oxepin, the initial metabolite of benzene, is presumed to give 1-(S-glutathionyl)-cyclohexa-3,5-dien-2-ol, which undergoes dehydration to S-phenylglutathione, the precursor of S-phenylmercapturic acid. To validate the proposed route to S-phenylglutathione, reactions of benzene oxide-oxepin with glutathione and other sulfur nucleophiles have been studied. The reaction of benzene oxide with an excess of aqueous sodium sulfide, followed by acetylation, gave bis-(6-trans-5-acetoxycyclohexa-1,3-dienyl)sulfide, the structure of which was proved by X-ray crystallography. Reactions of benzene oxide-oxepin in a 95:5 (v/v) mixture of phosphate buffer in D sub(2)O with (CD sub(3)) sub(2)SO were monitored by super(1)H NMR spectroscopy. In the absence of glutathione, the half-life of benzene oxide-oxepin was ca. 34 min at 25 degree C and pD 7.0. The half-life was not affected in the range of 2-15 mM glutathione in the presence and absence of a commercial sample of human glutathione S-transferase (at pH 7.0, 8.0, 8.5, or 10.0). The adduct 1-(S-glutathionyl)-cyclohexa-3,5-diene-2-ol was identified in these reaction mixtures, especially at higher pH, by mass spectrometry and by its acid-catalyzed decomposition to S-phenylglutathione. Incubation of benzene oxide with N-acetyl-L-cysteine at 37 degree C and pH 10.0 and subsequent mass spectrometric analysis of the mixture showed formation of pre-S-phenylmercapturic acid and the dehydration product, S-phenylmercapturic acid. The data validate the premise that benzene oxide-oxepin can be captured by glutathione to give (1R,2R)- and/or (1S,2S)-1-(S-glutathionyl)-cyclohexa-3,5-dien-2-ol, which dehydrate to S-phenylglutathione. The capture is a relatively inefficient process at pH 7 that is accelerated at higher pH. These studies account for the observation that the metabolism of benzene is dominated by the formation of phenol. The pathway leading to S-phenylmercapturic acid is necessarily minor on account of the low efficiency of benzene oxide capture by glutathione at pH 7 vs spontaneous rearrangement to phenol. JF - Chemical Research in Toxicology AU - Henderson, A P AU - Barnes, M L AU - Bleasdale, C AU - Cameron, R AU - Clegg, W AU - Heath, S L AU - Lindstrom, AB AU - Rappaport, S M AU - Waidyanatha, S AU - Watson, W P AU - Golding, B T AD - School of Natural Sciences-Chemistry, Bedson Building, University of Newcastle upon Tyne, Newcastle upon Tyne, NEI 7RU, United Kingdom Y1 - 2005/02/21/ PY - 2005 DA - 2005 Feb 21 SP - 265 EP - 270 VL - 18 IS - 2 SN - 0893-228X, 0893-228X KW - Toxicology Abstracts KW - Sulfur KW - Adducts KW - Metabolites KW - Glutathione transferase KW - biomarkers KW - Decomposition KW - Phenols KW - Benzene KW - X-ray crystallography KW - Sodium KW - Sulfide KW - Nucleophiles KW - Acetylation KW - N-Acetyl-L-cysteine KW - Phosphate KW - Magnetic resonance spectroscopy KW - Thiols KW - oxides KW - Metabolism KW - Dehydration KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17832570?accountid=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=Reactions+of+Benzene+Oxide+with+Thiols+Including+Glutathione&rft.au=Henderson%2C+A+P%3BBarnes%2C+M+L%3BBleasdale%2C+C%3BCameron%2C+R%3BClegg%2C+W%3BHeath%2C+S+L%3BLindstrom%2C+AB%3BRappaport%2C+S+M%3BWaidyanatha%2C+S%3BWatson%2C+W+P%3BGolding%2C+B+T&rft.aulast=Henderson&rft.aufirst=A&rft.date=2005-02-21&rft.volume=18&rft.issue=2&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/10.1021%2Ftx049781y LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Sulfur; Adducts; Metabolites; Glutathione transferase; Decomposition; biomarkers; Benzene; Phenols; Sodium; X-ray crystallography; Acetylation; Nucleophiles; Sulfide; N-Acetyl-L-cysteine; Phosphate; Magnetic resonance spectroscopy; Thiols; oxides; Metabolism; Dehydration DO - http://dx.doi.org/10.1021/tx049781y ER - TY - JOUR T1 - 3-nitropropionic acid-induced hydrogen peroxide, mitochondrial DNA damage, and cell death are attenuated by Bcl-2 overexpression in PC12 cells. AN - 67431070; 15710238 AB - 3-nitropropionic acid (3-NPA), a complex II inhibitor of the electron transport chain, causes Huntington disease-like symptoms after administration into animals. However, primary mechanisms of cell death are not clearly understood. This study tested the hypothesis that 3-NPA leads to the generation of reactive oxygen species (ROS), mitochondrial DNA damage, and loss of mitochondrial function. Amplex red and horseradish peroxidase were used to accurately measure the amount of H2O2, and showed that PC12 cells treated with 3-NPA (4 mM) lead to the production of hydrogen peroxide (1 nmol/10(6) cells/h). This amount of 3-NPA also leads to a rapid decline of ATP levels. There was time- and dose-dependent mitochondrial DNA damage following 3-NPA treatment. Overexpression of the proto-oncogene bcl-2 protects cells from apoptosis induced by various stimuli. Overexpression of Bcl-2 leads to almost threefold higher levels of ATP and also decreased the 3-NPA-mediated induction of hydrogen peroxide by over 50%. Bcl-2-overexpressing PC12 cells were also protected from mitochondrial DNA damage. These data show that ROS production followed by mitochondrial DNA damage is the primary event in 3-NPA toxicity, and Bcl-2 protects PC12 cells from 3-NPA toxicity by preventing mitochondrial DNA damage. JF - Brain research. Molecular brain research AU - Mandavilli, Bhaskar S AU - Boldogh, Istvan AU - Van Houten, Bennett AD - Laboratory of Molecular Genetics, National Institute of Environmental and Health Sciences, National Institutes of Health, 111 Alexander Drive, P.O. Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 2005/02/18/ PY - 2005 DA - 2005 Feb 18 SP - 215 EP - 223 VL - 133 IS - 2 SN - 0169-328X, 0169-328X KW - Convulsants KW - 0 KW - DNA, Mitochondrial KW - Nitro Compounds KW - Propionates KW - Proto-Oncogene Proteins c-bcl-2 KW - RNA, Messenger KW - Hydrogen Peroxide KW - BBX060AN9V KW - 3-nitropropionic acid KW - QY4L0FOX0D KW - Dihydrotachysterol KW - R5LM3H112R KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Dose-Response Relationship, Drug KW - Convulsants -- pharmacology KW - Reverse Transcriptase Polymerase Chain Reaction -- methods KW - Cell Death -- drug effects KW - Flow Cytometry -- methods KW - Rats KW - DNA, Mitochondrial -- drug effects KW - RNA, Messenger -- metabolism KW - Cell Survival -- drug effects KW - Cell Count -- methods KW - DNA, Mitochondrial -- metabolism KW - Gene Expression Regulation -- drug effects KW - Time Factors KW - PC12 Cells KW - Dihydrotachysterol -- metabolism KW - Hydrogen Peroxide -- metabolism KW - Proto-Oncogene Proteins c-bcl-2 -- physiology KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Propionates -- pharmacology KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67431070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=3-nitropropionic+acid-induced+hydrogen+peroxide%2C+mitochondrial+DNA+damage%2C+and+cell+death+are+attenuated+by+Bcl-2+overexpression+in+PC12+cells.&rft.au=Mandavilli%2C+Bhaskar+S%3BBoldogh%2C+Istvan%3BVan+Houten%2C+Bennett&rft.aulast=Mandavilli&rft.aufirst=Bhaskar&rft.date=2005-02-18&rft.volume=133&rft.issue=2&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-09 N1 - Date created - 2005-02-15 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 second-site mutations that restore function to a coupling-deficient mutant M3 receptor. AN - 67424745; 15572356 AB - The M(3) muscarinic receptor is a prototypical member of the class A family of G protein-coupled receptors (GPCRs). To gain insight into the structural mechanisms governing agonist-mediated M(3) receptor activation, we recently developed a genetically modified yeast strain (Saccharomyces cerevisiae) which allows the efficient screening of large libraries of mutant M(3) receptors to identify mutant receptors with altered/novel functional properties. Class A GPCRs contain a highly conserved Asp residue located in transmembrane domain II (TM II; corresponding to Asp-113 in the rat M(3) muscarinic receptor) which is of fundamental importance for receptor activation. As observed previously with other GPCRs analyzed in mammalian expression systems, the D113N point mutation abolished agonist-induced receptor/G protein coupling in yeast. We then subjected the D113N mutant M(3) receptor to PCR-based random mutagenesis followed by a yeast genetic screen to recover point mutations that can restore G protein coupling to the D113N mutant receptor. A large scale screening effort led to the identification of three such second-site suppressor mutations, R165W, R165M, and Y250D. When expressed in the wild-type receptor background, these three point mutations did not lead to an increase in basal activity and reduced the efficiency of receptor/G protein coupling. Similar results were obtained when the various mutant receptors were expressed and analyzed in transfected mammalian cells (COS-7 cells). Interestingly, like Asp-113, Arg-165 and Tyr-250, which are located at the cytoplasmic ends of TM III and TM V, respectively, are also highly conserved among class A GPCRs. Our data suggest a conformational link between the highly conserved Asp-113, Arg-165, and Tyr-250 residues which is critical for receptor activation. JF - The Journal of biological chemistry AU - Li, Bo AU - Nowak, Nicola M AU - Kim, Soo-Kyung AU - Jacobson, Kenneth A AU - Bagheri, Ali AU - Schmidt, Clarice AU - Wess, Jürgen AD - Department of Molecular Signaling, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, 8 Center Dr., Bethesda, MD 20892, USA. Y1 - 2005/02/18/ PY - 2005 DA - 2005 Feb 18 SP - 5664 EP - 5675 VL - 280 IS - 7 SN - 0021-9258, 0021-9258 KW - Ligands KW - 0 KW - Phosphatidylinositols KW - Receptor, Muscarinic M3 KW - Tyrosine KW - 42HK56048U KW - Arginine KW - 94ZLA3W45F KW - Index Medicus KW - Point Mutation -- genetics KW - Animals KW - Phosphatidylinositols -- metabolism KW - Arginine -- metabolism KW - COS Cells KW - Suppression, Genetic -- genetics KW - Radioligand Assay KW - Hydrolysis KW - Structure-Activity Relationship KW - Rats KW - Alleles KW - Arginine -- genetics KW - Tyrosine -- genetics KW - Tyrosine -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - Receptor, Muscarinic M3 -- metabolism KW - Mutagenesis -- genetics KW - Receptor, Muscarinic M3 -- chemistry KW - Receptor, Muscarinic M3 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67424745?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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%3A+identification+of+second-site+mutations+that+restore+function+to+a+coupling-deficient+mutant+M3+receptor.&rft.au=Li%2C+Bo%3BNowak%2C+Nicola+M%3BKim%2C+Soo-Kyung%3BJacobson%2C+Kenneth+A%3BBagheri%2C+Ali%3BSchmidt%2C+Clarice%3BWess%2C+J%C3%BCrgen&rft.aulast=Li&rft.aufirst=Bo&rft.date=2005-02-18&rft.volume=280&rft.issue=7&rft.spage=5664&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 - 2005-04-18 N1 - Date created - 2005-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Zinc concentration in esophageal biopsy specimens measured by x-ray fluorescence and esophageal cancer risk. AN - 67438091; 15713965 AB - In rodents, zinc deficiency potentiates the effects of certain nitrosamines that act as esophageal carcinogens. Studies of the association between zinc and esophageal squamous cell carcinoma in humans have been hampered by plasma zinc homeostasis, which obscures individual differences in total zinc stores, and by the uncertainty regarding zinc bioavailability when estimating dietary zinc intake because phytate from whole grains effectively prohibits zinc absorption. By using baseline tissue biopsy specimens collected in a prospective observational study, we determined the association between incident esophageal squamous cell carcinoma and baseline element concentrations in tissue sections from residents of Linzhou, China, participating in a nutrition intervention trial. We used x-ray fluorescence spectroscopy to measure zinc, copper, iron, nickel, and sulfur concentrations in single 5-microm-thick sections from formalin-fixed, paraffin-embedded esophageal biopsy specimens collected in 1985 from 60 eventual case and 72 control subjects. Subjects were matched on baseline histology and followed for 16 years. We used Cox proportional hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between each element and risk of incident esophageal cancer. All statistical tests were two-sided. The risk of developing esophageal cancer was much lower for subjects in the highest quartile of esophageal tissue zinc concentration compared with those in the lowest quartile (HR = 0.21, 95% CI = 0.065 to 0.68). The association was statistically significant across quartiles (P(trend) = .015). Individuals in the highest quartile of sulfur concentration had a lower risk of esophageal cancer than individuals in the lowest quartile (HR = 0.29, 95% CI = 0.095 to 0.85), but the association across quartiles was not statistically significant (P(trend) = .081). There was no association between copper, iron, or nickel concentrations and risk of esophageal cancer. High tissue zinc concentration was strongly associated with a reduced risk of developing esophageal squamous cell carcinoma. X-ray fluorescence spectroscopy can be used to assess relationships among concentrations of both nutritional and toxic elements and disease risk in banked tissue specimens. JF - Journal of the National Cancer Institute AU - Abnet, Christian C AU - Lai, Barry AU - Qiao, You-Lin AU - Vogt, Stefan AU - Luo, Xian-Mao AU - Taylor, Philip R AU - Dong, Zhi-Wei AU - Mark, Steven D AU - Dawsey, Sanford M AD - Cancer Prevention Studies Branch, National Cancer Institute, National Institutes of Health, 6116 Executive Blvd., Rm. 705, Bethesda, MD 20892, USA. abnetc@mail.nih.gov Y1 - 2005/02/16/ PY - 2005 DA - 2005 Feb 16 SP - 301 EP - 306 VL - 97 IS - 4 KW - Sulfur KW - 70FD1KFU70 KW - Copper KW - 789U1901C5 KW - Nickel KW - 7OV03QG267 KW - Iron KW - E1UOL152H7 KW - Zinc KW - J41CSQ7QDS KW - Index Medicus KW - Odds Ratio KW - Iron -- analysis KW - Spectrometry, X-Ray Emission KW - Humans KW - Nickel -- analysis KW - Biopsy KW - China -- epidemiology KW - Case-Control Studies KW - Confidence Intervals KW - Incidence KW - Copper -- analysis KW - Sulfur -- analysis KW - Proportional Hazards Models KW - Zinc -- analysis KW - Carcinoma, Squamous Cell -- epidemiology KW - Carcinoma, Squamous Cell -- pathology KW - Esophageal Neoplasms -- chemistry KW - Carcinoma, Squamous Cell -- chemistry KW - Esophageal Neoplasms -- pathology KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67438091?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+concentration+in+esophageal+biopsy+specimens+measured+by+x-ray+fluorescence+and+esophageal+cancer+risk.&rft.au=Abnet%2C+Christian+C%3BLai%2C+Barry%3BQiao%2C+You-Lin%3BVogt%2C+Stefan%3BLuo%2C+Xian-Mao%3BTaylor%2C+Philip+R%3BDong%2C+Zhi-Wei%3BMark%2C+Steven+D%3BDawsey%2C+Sanford+M&rft.aulast=Abnet&rft.aufirst=Christian&rft.date=2005-02-16&rft.volume=97&rft.issue=4&rft.spage=301&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 - 2005-02-22 N1 - Date created - 2005-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toll-Like Receptor 4 on Nonhematopoietic Cells Sustains CNS Inflammation during Endotoxemia, Independent of Systemic Cytokines AN - 17620322; 6172873 AB - Inflammatory agonists such as lipopolysaccharide (LPS) induce robust systemic as well as CNS responses after peripheral administration. Responses in the innate immune system require triggering of toll-like receptor 4 (TLR4), but the origin of CNS sequelas has been controversial. We demonstrate expression of TLR4 transcripts in mouse brain in the meninges, ventricular ependyma, circumventricular organs, along the vasculature, and in parenchymal microglia. The contribution of TLR4 expressed in CNS resident versus hematopoietic cells to the development of CNS inflammation was examined using chimeric mice. Reciprocal bone marrow chimeras between wild-type and TLR4 mutant mice show that TLR4 on CNS resident cells is critically required for sustained inflammation in the brain after systemic LPS administration. Hematopoietic TLR4 alone supported the systemic release of acute phase cytokines, but transcription of proinflammatory genes in the CNS was reduced in duration. In contrast, TLR4 function in radiation-resistant cells was sufficient for inflammatory progression in the brains of chimeric mice, despite the striking absence of cytokine elevations in serum. Surprisingly, a temporal rise in serum corticosterone was also dependent on TLR4 signaling in nonhematopoietic cells. Our findings demonstrate a requirement for TLR4 function in CNS-resident cells, independent of systemic cytokine effects, for sustained CNS-specific inflammation and corticosterone rise during endotoxemia. JF - Journal of Neuroscience AU - Chakravarty, Sumana AU - Herkenham, Miles AD - Section on Functional Neuroanatomy, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland Y1 - 2005/02/16/ PY - 2005 DA - 2005 Feb 16 SP - 1788 EP - 1796 PB - Society for Neuroscience, 11 Dupont Circle, N.W. Suite 500 Washington DC 20036 USA, [mailto:info@sfn.org], [URL:http://apu.sfn.org/] VL - 25 IS - 7 SN - 0270-6474, 0270-6474 KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - N3 11104:Mammals (except primates) KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17620322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neuroscience&rft.atitle=Toll-Like+Receptor+4+on+Nonhematopoietic+Cells+Sustains+CNS+Inflammation+during+Endotoxemia%2C+Independent+of+Systemic+Cytokines&rft.au=Chakravarty%2C+Sumana%3BHerkenham%2C+Miles&rft.aulast=Chakravarty&rft.aufirst=Sumana&rft.date=2005-02-16&rft.volume=25&rft.issue=7&rft.spage=1788&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-09-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - HA22 (R490A) is a recombinant immunotoxin with increased antitumor activity without an increase in animal toxicity. AN - 67481725; 15746059 AB - RFB4 (dsFv)-PE38 (BL22) is a recombinant immunotoxin containing an anti-CD22 (Fv) fused to truncated Pseudomonas exotoxin A, which induces a high complete remission rate in patients with purine analogue-resistant hairy cell leukemia. HA22 is a mutant of BL22 with mutations in heavy-chain CDR3 resulting in increased cytotoxic activity. Our goal was to improve the activity of HA22. Arg(490), which is located in the catalytic domain (III) of the immunotoxin HA22, was mutated to alanine. Purified immunotoxins were produced and tested for cytotoxic activity in cell culture and for antitumor activity and nonspecific toxicity in mice. ADP-ribosylation activity was also measured. HA22 (R490A) is approximately 2-fold more cytotoxic than HA22 on several CD22-positive cell lines. When injected i.v., HA22 (R490A) has more potent antitumor activity than HA22 against CA46 tumors in mice. HA22 and HA22 (R490A) have similar LD(50)s (approximately 1.3 mg/kg) and similar plasma half-lives. The R490A mutation also improved the cytotoxicity of the antimesothelin recombinant immunotoxin SS1 (dsFv)-PE38 (SS1P). In vitro ADP-ribosylation assays show that HA22 R490A has increased activity. Increased cytotoxic activity is probably related to this increase in ADP-ribosylation activity. Protein engineering can be used to increase the efficacy of recombinant immunotoxins. Because HA22 (R490A) has increased antitumor activity without increased animal toxicity, immunotoxins with this mutation are candidates for clinical development. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Bang, Sookhee AU - Nagata, Satoshi AU - Onda, Masanori AU - Kreitman, Robert J AU - Pastan, Ira AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD 20892, USA. Y1 - 2005/02/15/ PY - 2005 DA - 2005 Feb 15 SP - 1545 EP - 1550 VL - 11 IS - 4 SN - 1078-0432, 1078-0432 KW - Antibodies KW - 0 KW - Antigens, CD KW - Antigens, Differentiation, B-Lymphocyte KW - Antineoplastic Agents KW - Bacterial Toxins KW - CD22 protein, human KW - Cd22 protein, mouse KW - Cell Adhesion Molecules KW - Enterotoxins KW - Exotoxins KW - GPI-Linked Proteins KW - Immunotoxins KW - Lectins KW - Membrane Glycoproteins KW - RFB4(dsFv)-PE38 recombinant immunotoxin KW - Sialic Acid Binding Ig-like Lectin 2 KW - mesothelin KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Index Medicus KW - Animals KW - Cell Adhesion Molecules -- genetics KW - Antigens, Differentiation, B-Lymphocyte -- genetics KW - Cell Adhesion Molecules -- immunology KW - Humans KW - Antigens, CD -- genetics KW - Adenosine Diphosphate Ribose -- metabolism KW - Bacterial Toxins -- genetics KW - Cell Survival -- drug effects KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Lectins -- genetics KW - Xenograft Model Antitumor Assays KW - Inhibitory Concentration 50 KW - Membrane Glycoproteins -- genetics KW - Exotoxins -- genetics KW - Cell Line, Tumor KW - Mice KW - Mice, SCID KW - Mutation KW - Membrane Glycoproteins -- immunology KW - Cell Line KW - Antigens, CD -- immunology KW - Female KW - Lectins -- immunology KW - Immunotoxins -- toxicity KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- toxicity KW - Immunotoxins -- genetics KW - Immunotoxins -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67481725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=HA22+%28R490A%29+is+a+recombinant+immunotoxin+with+increased+antitumor+activity+without+an+increase+in+animal+toxicity.&rft.au=Bang%2C+Sookhee%3BNagata%2C+Satoshi%3BOnda%2C+Masanori%3BKreitman%2C+Robert+J%3BPastan%2C+Ira&rft.aulast=Bang&rft.aufirst=Sookhee&rft.date=2005-02-15&rft.volume=11&rft.issue=4&rft.spage=1545&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 - 2005-07-28 N1 - Date created - 2005-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taxanes with anthracyclines as first-line chemotherapy for metastatic breast carcinoma. AN - 67435382; 15637696 AB - The magnitude of the benefit of adding taxanes to anthracyclines in first-line chemotherapy for metastatic breast carcinoma is still unclear. The authors performed a pooled analysis as well as a meta-analysis of all Phase III trials, to determine whether the combination of anthracyclines plus taxanes provided an advantage over standard anthracyclines-based regimens. All Phase III peer-reviewed published or presented trials were considered eligible. A pooled analysis (Method A) and a literature-based meta-analysis (Method B) were accomplished, and event-based relative risk ratios (RR(A-B)) with 95% confidence intervals were derived. Both analyses were performed to examine for significant differences in time to disease progression (TTP), overall response rate (ORR), overall survival (OS), complete response rate (CR), neutropenia, and febrile neutropenia (FN). For both analyses, a heterogeneity test was applied. Seven trials (2805 patients) were gathered. When data were pooled and plotted, significant differences in favor of taxanes were seen for ORR (RR(A-B) 1.21, P<0.001), CR (RR(A) 2.04; RR(B) 1.81, P<0.001), even though they caused a significant increase in neutropenia (RR(A) 1.19; RR(B) 1.15, P<0.001) and FN (RR(A) 2.82; RR(B) 3.44, P<0.001). A borderline significance in favor of taxanes was seen in TTP (RR(A) 1.10, P=0.05; RR(B) 1.06, P=0.07). A nonsignificant trend for taxanes was found in OS. No significant heterogeneity (except for neutropenia, P<0.01) was observed. The adjunction of taxanes to anthracyclines in first-line chemotherapy for metastatic breast carcinoma yielded a significant benefit in activity (ORR, CR), a slight advantage in TTP, and a trend in OS, although with a significant cost in hematologic toxicity. Copyright (c) 2005 American Cancer Society. JF - Cancer AU - Bria, Emilio AU - Giannarelli, Diana AU - Felici, Alessandra AU - Peters, William P AU - Nisticò, Cecilia AU - Vanni, Barbara AU - Cuppone, Federica AU - Cognetti, Francesco AU - Terzoli, Edmondo AD - Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy. emiliobria@yahoo.it Y1 - 2005/02/15/ PY - 2005 DA - 2005 Feb 15 SP - 672 EP - 679 VL - 103 IS - 4 SN - 0008-543X, 0008-543X KW - Anthracyclines KW - 0 KW - Antineoplastic Agents KW - Taxoids KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Taxoids -- adverse effects KW - Clinical Trials as Topic KW - Anthracyclines -- adverse effects KW - Survival Analysis KW - Antineoplastic Agents -- adverse effects KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- mortality KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67435382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Taxanes+with+anthracyclines+as+first-line+chemotherapy+for+metastatic+breast+carcinoma.&rft.au=Bria%2C+Emilio%3BGiannarelli%2C+Diana%3BFelici%2C+Alessandra%3BPeters%2C+William+P%3BNistic%C3%B2%2C+Cecilia%3BVanni%2C+Barbara%3BCuppone%2C+Federica%3BCognetti%2C+Francesco%3BTerzoli%2C+Edmondo&rft.aulast=Bria&rft.aufirst=Emilio&rft.date=2005-02-15&rft.volume=103&rft.issue=4&rft.spage=672&rft.isbn=&rft.btitle=&rft.title=Cancer&rft.issn=0008543X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-29 N1 - Date created - 2005-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural mechanism for ubiquitinated-cargo recognition by the Golgi-localized, gamma-ear-containing, ADP-ribosylation-factor-binding proteins. AN - 67433072; 15701688 AB - The Golgi-localized, gamma-ear-containing, Arf (ADP-ribosylation factor)-binding (GGA) proteins are clathrin adaptors that mediate the sorting of transmembrane-cargo molecules at the trans-Golgi network and endosomes. Cargo proteins can be directed into the GGA pathway by at least two different types of sorting signals: acidic cluster-dileucine motifs and covalent modification by ubiquitin. The latter modification is recognized by the GGAs through binding to their GAT [GGA and TOM (target of Myb)] domain. Here we report the crystal structure of the GAT domain of human GGA3 in a 1:1 complex with ubiquitin at 2.8-A resolution. Ubiquitin binds to a hydrophobic and acidic patch on helices alpha1 and alpha2 of the GAT three-helix bundle that includes Asn-223, Leu-227, Glu-230, Met-231, Asp-244, Glu-246, Leu-247, Glu-250, and Leu-251. The GAT-binding surface on ubiquitin is a hydrophobic patch centered on Ile-44 that is also responsible for binding most other ubiquitin effectors. The ubiquitin-binding site observed in the crystal is distinct from the Rabaptin-5-binding site on helices alpha2 and alpha3 of the GAT domain. Mutational analysis and modeling of the ubiquitin-Rabaptin-5-GAT ternary complex indicates that ubiquitin and Rabaptin-5 can bind to the GAT domain at two different sites without any steric conflict. This ability highlights the GAT domain as a hub for interactions with multiple partners in trafficking. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Prag, Gali AU - Lee, Sangho AU - Mattera, Rafael AU - Arighi, Cecilia N AU - Beach, Bridgette M AU - Bonifacino, Juan S AU - Hurley, James H AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2005/02/15/ PY - 2005 DA - 2005 Feb 15 SP - 2334 EP - 2339 VL - 102 IS - 7 SN - 0027-8424, 0027-8424 KW - Adaptor Proteins, Vesicular Transport KW - 0 KW - GGA adaptor proteins KW - Multiprotein Complexes KW - RABEP1 protein, human KW - Recombinant Proteins KW - Ubiquitin KW - Vesicular Transport Proteins KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - Index Medicus KW - Molecular Structure KW - Models, Molecular KW - Humans KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Binding Sites KW - Static Electricity KW - Mutagenesis, Site-Directed KW - Ubiquitin -- metabolism KW - Ubiquitin -- chemistry KW - Recombinant Proteins -- metabolism KW - In Vitro Techniques KW - Molecular Sequence Data KW - Crystallography, X-Ray KW - Vesicular Transport Proteins -- metabolism KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Golgi Apparatus -- metabolism KW - Vesicular Transport Proteins -- chemistry KW - Protein Conformation KW - ADP-Ribosylation Factors -- genetics KW - ADP-Ribosylation Factors -- metabolism KW - Adaptor Proteins, Vesicular Transport -- metabolism KW - Adaptor Proteins, Vesicular Transport -- chemistry KW - ADP-Ribosylation Factors -- chemistry KW - Adaptor Proteins, Vesicular Transport -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67433072?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structural+mechanism+for+ubiquitinated-cargo+recognition+by+the+Golgi-localized%2C+gamma-ear-containing%2C+ADP-ribosylation-factor-binding+proteins.&rft.au=Prag%2C+Gali%3BLee%2C+Sangho%3BMattera%2C+Rafael%3BArighi%2C+Cecilia+N%3BBeach%2C+Bridgette+M%3BBonifacino%2C+Juan+S%3BHurley%2C+James+H&rft.aulast=Prag&rft.aufirst=Gali&rft.date=2005-02-15&rft.volume=102&rft.issue=7&rft.spage=2334&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 - 2005-04-13 N1 - Date created - 2005-02-16 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1YD8; PDB N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):861-6 [8570649] J Mol Biol. 1993 Dec 20;234(4):946-50 [8263940] Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21 [9757107] Protein Expr Purif. 1999 Feb;15(1):34-9 [10024467] EMBO J. 2004 Nov 10;23(22):4371-83 [15496985] J Biol Chem. 2004 Dec 24;279(52):54808-16 [15494413] Nat Rev Mol Cell Biol. 2001 Mar;2(3):195-201 [11265249] Acta Crystallogr D Biol Crystallogr. 2001 Aug;57(Pt 8):1127-34 [11468396] J Biol Chem. 2001 Aug 10;276(32):30483-9 [11399765] Nat Rev Mol Cell Biol. 2002 Dec;3(12):893-905 [12461556] EMBO J. 2003 Jan 2;22(1):78-88 [12505986] Dev Cell. 2003 Mar;4(3):321-32 [12636914] Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4451-6 [12668765] Nat Struct Biol. 2003 May;10(5):386-93 [12679809] Biochemistry. 2003 Jun 3;42(21):6392-9 [12767220] Nat Rev Mol Cell Biol. 2003 Jun;4(6):491-7 [12778128] Cell. 2003 May 30;113(5):609-20 [12787502] Cell. 2003 May 30;113(5):621-30 [12787503] EMBO J. 2003 Sep 15;22(18):4597-606 [12970172] Trends Biochem Sci. 2003 Nov;28(11):598-603 [14607090] Acta Crystallogr D Biol Crystallogr. 2003 Dec;59(Pt 12):2237-41 [14646082] J Biol Chem. 2003 Dec 26;278(52):52865-72 [14563850] Nat Rev Mol Cell Biol. 2004 Jan;5(1):23-32 [14708007] J Biol Chem. 2004 Feb 20;279(8):7105-11 [14660606] Nat Cell Biol. 2004 Mar;6(3):244-51 [15039775] Nat Cell Biol. 2004 Mar;6(3):252-9 [15039776] Mol Cell. 2004 Mar 26;13(6):783-9 [15053872] EMBO J. 2004 Apr 7;23(7):1411-21 [15029239] J Biol Chem. 2004 Jun 4;279(23):24435-43 [15047686] Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W606-9 [15215460] J Biol Chem. 2004 Jul 2;279(27):28689-96 [15044434] J Biol Chem. 2004 Jul 23;279(30):31409-18 [15143060] EMBO J. 2004 Oct 1;23(19):3701-10 [15359277] EMBO J. 2004 Oct 13;23(20):3909-17 [15457209] J Biol Chem. 2004 Oct 29;279(44):46191-203 [15292237] Eur J Cell Biol. 2004 Jul;83(6):257-62 [15511083] Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 [2025413] Methods Enzymol. 1997;276:344-58 [9048378] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TGF-beta and vitamin D3 utilize distinct pathways to suppress IL-12 production and modulate rapid differentiation of human monocytes into CD83+ dendritic cells. AN - 67413126; 15699136 AB - We previously demonstrated that agents known to signal infection or inflammation can rapidly and directly drive differentiation of human CD14+ monocytes into CD83+ dendritic cells (DCs) when introduced to cells under serum-free conditions. In this study, we evaluated the effects of TGF-beta and vitamin D3 (VitD3) on the proportion and function of monocytes that adopt DC characteristics. TGF-beta significantly decreased the proportion of cells that rapidly adopted stable DC characteristics in response to LPS, but had little or no effect on calcium ionophore-induced differentiation. In contrast, VitD3 showed no such pathway specificity and dramatically suppressed differentiation of monocytes into DCs in response to these agents. Both TGF-beta and VitD3 altered cytokine and chemokine production in LPS-treated monocytes, inhibited IL-12 and IL-10 secretion, and decreased the functional capacity of DCs. Despite the similar effects of TGF-beta and VitD3, there are significant differences in the signaling pathways used by these agents, as evidenced by their distinct effects on LPS- and calcium ionophore-induced DC differentiation, on LPS-induced secretion of IL-10, and on two members of the NF-kappaB family of transcription factors, RelB and cRel. These studies identify TGF-beta and VitD3 as potent regulatory factors that use distinct pathways to suppress both the differentiation of DCs as well as their capacity to secrete the Th1-polarizing cytokine IL-12. Because these agents are present in serum and negatively affect DC differentiation at physiological concentrations, our findings are likely to have significance regarding the in vivo role of TGF-beta and VitD3 in determining the type of immune responses. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Lyakh, Lyudmila A AU - Sanford, Michael AU - Chekol, Sebel AU - Young, Howard A AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2005/02/15/ PY - 2005 DA - 2005 Feb 15 SP - 2061 EP - 2070 VL - 174 IS - 4 SN - 0022-1767, 0022-1767 KW - Antigens, CD KW - 0 KW - CD83 antigen KW - Culture Media, Serum-Free KW - DNA-Binding Proteins KW - Immunoglobulins KW - Immunologic Factors KW - Lipopolysaccharides KW - Membrane Glycoproteins KW - NF-kappa B KW - Receptors, Cell Surface KW - Smad Proteins KW - Toll-Like Receptors KW - Trans-Activators KW - Transforming Growth Factor beta KW - Interleukin-12 KW - 187348-17-0 KW - Cholecalciferol KW - 1C6V77QF41 KW - p38 Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Abridged Index Medicus KW - Index Medicus KW - Trans-Activators -- metabolism KW - Lipopolysaccharides -- antagonists & inhibitors KW - Humans KW - Lipopolysaccharides -- pharmacology KW - Lymphocyte Culture Test, Mixed KW - Down-Regulation -- immunology KW - Receptors, Cell Surface -- biosynthesis KW - p38 Mitogen-Activated Protein Kinases -- metabolism KW - Cell Differentiation -- immunology KW - Active Transport, Cell Nucleus -- immunology KW - p38 Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Monocytes -- cytology KW - Cells, Cultured KW - Monocytes -- immunology KW - Monocytes -- metabolism KW - Antigen-Presenting Cells -- immunology KW - Immunophenotyping KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors KW - DNA-Binding Proteins -- metabolism KW - Dendritic Cells -- immunology KW - Transforming Growth Factor beta -- physiology KW - Membrane Glycoproteins -- biosynthesis KW - Immunologic Factors -- physiology KW - Dendritic Cells -- metabolism KW - Cholecalciferol -- physiology KW - Interleukin-12 -- biosynthesis KW - Signal Transduction -- immunology KW - Immunoglobulins -- biosynthesis KW - Interleukin-12 -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67413126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=TGF-beta+and+vitamin+D3+utilize+distinct+pathways+to+suppress+IL-12+production+and+modulate+rapid+differentiation+of+human+monocytes+into+CD83%2B+dendritic+cells.&rft.au=Lyakh%2C+Lyudmila+A%3BSanford%2C+Michael%3BChekol%2C+Sebel%3BYoung%2C+Howard+A%3BRoberts%2C+Anita+B&rft.aulast=Lyakh&rft.aufirst=Lyudmila&rft.date=2005-02-15&rft.volume=174&rft.issue=4&rft.spage=2061&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 - 2005-03-29 N1 - Date created - 2005-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic production of lung free radicals by diesel exhaust particles and endotoxin. AN - 67408570; 15477498 AB - The present study tested the hypothesis that free radicals were involved in the pathogenesis of lung injury caused by diesel exhaust particles (DEP) and bacterial lipopolysaccharides (LPS). Intratracheal coinstillation of DEP and LPS in rat lungs resulted in synergistic enhancement of free radical generation in the lungs. The radical metabolites were characterized as lipid-derived by electron spin resonance (ESR). The free radical generation was paralleled by a synergistic increase in total protein and by infiltration of neutrophils in the bronchoalveolar lavage (BAL) fluid of the lungs. Experiments with NADP-reduced (NADPH) oxidase and iNOS knockout mice showed that NADPH oxidase and iNOS did not contribute to free radical generation. However, pretreatment with the macrophage toxicant GdCl(3), the xanthine oxidase (XO) inhibitor allopurinol, and the Fe(III) chelator Desferal resulted in a marked decrease in free radical generation, lung inflammation, and lung injury. These effects were concomitant with the inhibition of XO activity in BAL, suggesting that the activated macrophages and the activity of XO contributed to the generation of free radicals caused by DEP and LPS. This is the first demonstration that DEP and LPS work synergistically to enhance free radical generation in lungs, mediated by the activation of local XO. JF - American journal of respiratory and critical care medicine AU - Arimoto, Toyoko AU - Kadiiska, Maria B AU - Sato, Keizo AU - Corbett, Jean AU - Mason, Ronald P AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 2005/02/15/ PY - 2005 DA - 2005 Feb 15 SP - 379 EP - 387 VL - 171 IS - 4 SN - 1073-449X, 1073-449X KW - Anti-Inflammatory Agents KW - 0 KW - Endotoxins KW - Free Radical Scavengers KW - Free Radicals KW - Iron Chelating Agents KW - Lipopolysaccharides KW - Vehicle Emissions KW - Xanthine KW - 1AVZ07U9S7 KW - Allopurinol KW - 63CZ7GJN5I KW - Gadolinium KW - AU0V1LM3JT KW - Xanthine Oxidase KW - EC 1.17.3.2 KW - Deferoxamine KW - J06Y7MXW4D KW - gadolinium chloride KW - P7082WY76D KW - Abridged Index Medicus KW - Index Medicus KW - Xanthine Oxidase -- metabolism KW - Animals KW - Xanthine Oxidase -- antagonists & inhibitors KW - Iron Chelating Agents -- administration & dosage KW - Xanthine -- metabolism KW - Disease Models, Animal KW - Free Radical Scavengers -- administration & dosage KW - Mice KW - Anti-Inflammatory Agents -- administration & dosage KW - Deferoxamine -- administration & dosage KW - Mice, Knockout KW - Rats KW - Allopurinol -- administration & dosage KW - Electron Spin Resonance Spectroscopy -- methods KW - Rats, Sprague-Dawley KW - Gadolinium -- administration & dosage KW - Bronchoalveolar Lavage Fluid -- chemistry KW - Up-Regulation -- drug effects KW - Drug Synergism KW - Male KW - Lung Diseases -- drug therapy KW - Vehicle Emissions -- toxicity KW - Lung Diseases -- chemically induced KW - Lung Diseases -- pathology KW - Lung -- drug effects KW - Lipopolysaccharides -- toxicity KW - Lung -- metabolism KW - Free Radicals -- metabolism KW - Endotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67408570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Synergistic+production+of+lung+free+radicals+by+diesel+exhaust+particles+and+endotoxin.&rft.au=Arimoto%2C+Toyoko%3BKadiiska%2C+Maria+B%3BSato%2C+Keizo%3BCorbett%2C+Jean%3BMason%2C+Ronald+P&rft.aulast=Arimoto&rft.aufirst=Toyoko&rft.date=2005-02-15&rft.volume=171&rft.issue=4&rft.spage=379&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 - 2005-03-15 N1 - Date created - 2005-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of key amino acids in the gastrin-releasing peptide receptor (GRPR) responsible for high affinity binding of gastrin-releasing peptide (GRP). AN - 67379839; 15670577 AB - The bombesin (Bn) receptor family includes the gastrin-releasing peptide (GRPR) and neuromedin B (NMBR) receptors, Bn receptor subtype 3 (BRS-3) and Bn receptor subtype 4 (BB(4)). They share 50% homology, yet their affinities for gastrin-releasing peptide (GRP) differ. The determinants of GRP high affinity for GRPR and BB(4), and low affinity for BRS-3 are largely unknown. To address this question we made an analysis of structural homologies in Bn receptor members correlated with their affinities for GRP to develop criteria to identify amino acids important for GRP selectivity. Fourteen differences were identified and each was mutated singly in GRPR to that found in hBRS-3. Eleven mutants had a loss of GRP affinity. Furthermore, three of four amino acids in the GRPR selected used a similar approach and previously reported to be important for high affinity Bn binding, were important for GRP affinity. Some GRPR mutants containing combinations of these mutations had greater decreases in GRP affinity than any single mutation. Particularly important for GRP selectivity were K101, Q121, A198, P199, S293, R288, T297 in GRPR. These results were confirmed by making the reverse mutations in BRS-3 to make GRP gain of affinity mutants. Modeling studies demonstrated a number of the important amino acids had side-chains oriented inward and within 6A of the binding pocket. These results demonstrated this approach could identify amino acids needed for GRP affinity and complemented results from chimera/mutagenesis studies by identifying which differences in the extracellular domains of Bn receptors were important for GRP affinity. JF - Biochemical pharmacology AU - Nakagawa, Tomoo AU - Hocart, Simon J AU - Schumann, Michael AU - Tapia, Jose A AU - Mantey, Samuel A AU - Coy, David H AU - Tokita, Kenji AU - Katsuno, Tatsuro AU - Jensen, Robert T AD - Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892-1804, USA. Y1 - 2005/02/15/ PY - 2005 DA - 2005 Feb 15 SP - 579 EP - 593 VL - 69 IS - 4 SN - 0006-2952, 0006-2952 KW - Receptors, Bombesin KW - 0 KW - Gastrin-Releasing Peptide KW - 80043-53-4 KW - Index Medicus KW - Animals KW - BALB 3T3 Cells KW - Models, Molecular KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Binding Sites KW - Gastrin-Releasing Peptide -- metabolism KW - Receptors, Bombesin -- metabolism KW - Receptors, Bombesin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67379839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+key+amino+acids+in+the+gastrin-releasing+peptide+receptor+%28GRPR%29+responsible+for+high+affinity+binding+of+gastrin-releasing+peptide+%28GRP%29.&rft.au=Nakagawa%2C+Tomoo%3BHocart%2C+Simon+J%3BSchumann%2C+Michael%3BTapia%2C+Jose+A%3BMantey%2C+Samuel+A%3BCoy%2C+David+H%3BTokita%2C+Kenji%3BKatsuno%2C+Tatsuro%3BJensen%2C+Robert+T&rft.aulast=Nakagawa&rft.aufirst=Tomoo&rft.date=2005-02-15&rft.volume=69&rft.issue=4&rft.spage=579&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 - 2005-03-07 N1 - Date created - 2005-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analyses of Recombinant Vaccinia and Fowlpox Vaccine Vectors Expressing Transgenes for Two Human Tumor Antigens and Three Human Costimulatory Molecules AN - 19929553; 6188066 AB - PURPOSE: The poor immunogenicity of tumor antigens and the antigenic heterogeneity of tumors call for vaccine strategies to enhance T-cell responses to multiple antigens. Two antigens expressed noncoordinately on most human carcinomas are carcinoembryonic antigen (CEA) and MUC-1. We report here the construction and characterization of two viral vector vaccines to address these issues. Experimental Design: The two viral vectors analyzed are the replication- competent recombinant vaccinia virus (rV-) and the avipox vector, fowlpox (rF-), which is replication incompetent in mammalian cells. Each vector encodes the transgenes for three human costimulatory molecules (B7-1, ICAM-1, and LFA-3, designated TRICOM) and the CEA and MUC-1 transgenes (which also contain agonist epitopes). The vectors are designated rV-CEA/MUC/TRICOM and rF-CEA/MUC/TRICOM. RESULTS: Each of the vectors is shown to be capable of faithfully expressing all five transgenes in human dendritic cells (DC). DCs infected with either vector are shown to activate both CEA-and MUC-1-specific T-cell lines to the same level as DCs infected with CEA-TRICOM or MUC-1-TRICOM vectors. Thus, no evidence of antigenic competition between CEA and MUC-1 was observed. Human DCs infected with rV-CEA/MUC/TRICOM or rF-CEA/MUC/TRICOM are also shown to be capable of generating both MUC-1-and CEA-specific T-cell lines; these T-cell lines are in turn shown to be capable of lysing targets pulsed with MUC-1 or CEA peptides as well as human tumor cells endogenously expressing MUC-1 and/or CEA. CONCLUSION: These studies provide the rationale for the clinical evaluation of these multigene vectors in patients with a range of carcinomas expressing MUC-1 and/or CEA. JF - Clinical Cancer Research AU - Tsang, Kwong Y AU - Palena, Claudia AU - Yokokawa, Junko AU - Arlen, Philip M AU - Gulley, James L AU - Mazzara, Gail P AU - Gritz, Linda AU - Gomez Yafal, Alicia AU - Ogueta, Sandra AU - Greenhalgh, Patricia AU - Manson, Kelledy AU - Panicali, Dennis AU - Schlom, Jeffrey AD - Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland and Therion Biologics Corporation, Cambridge, Massachusetts Y1 - 2005/02/15/ PY - 2005 DA - 2005 Feb 15 SP - 1597 EP - 1607 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 11 IS - 4 SN - 1078-0432, 1078-0432 KW - Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts; Immunology Abstracts KW - Fowlpox KW - Vaccinia KW - Replication KW - Carcinoembryonic antigen KW - Transgenes KW - CD58 antigen KW - Tumors KW - Tumor cells KW - Carcinoma KW - Antigenic competition KW - Costimulator KW - Dendritic cells KW - B7-1 antigen KW - Vaccinia virus KW - Mammalian cells KW - Immunogenicity KW - Antigen (tumor-associated) KW - intercellular adhesion molecule 1 KW - Lymphocytes T KW - Vaccines KW - Epitopes KW - V 22350:Immunology KW - F 06915:Cancer Immunology KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19929553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Analyses+of+Recombinant+Vaccinia+and+Fowlpox+Vaccine+Vectors+Expressing+Transgenes+for+Two+Human+Tumor+Antigens+and+Three+Human+Costimulatory+Molecules&rft.au=Tsang%2C+Kwong+Y%3BPalena%2C+Claudia%3BYokokawa%2C+Junko%3BArlen%2C+Philip+M%3BGulley%2C+James+L%3BMazzara%2C+Gail+P%3BGritz%2C+Linda%3BGomez+Yafal%2C+Alicia%3BOgueta%2C+Sandra%3BGreenhalgh%2C+Patricia%3BManson%2C+Kelledy%3BPanicali%2C+Dennis%3BSchlom%2C+Jeffrey&rft.aulast=Tsang&rft.aufirst=Kwong&rft.date=2005-02-15&rft.volume=11&rft.issue=4&rft.spage=1597&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-07-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Fowlpox; Replication; Vaccinia; Transgenes; Carcinoembryonic antigen; CD58 antigen; Tumors; Tumor cells; Antigenic competition; Carcinoma; B7-1 antigen; Dendritic cells; Costimulator; Mammalian cells; Immunogenicity; intercellular adhesion molecule 1; Antigen (tumor-associated); Lymphocytes T; Vaccines; Epitopes; Vaccinia virus ER - TY - JOUR T1 - Serologic Correlates of Protection against Enterotoxigenic Escherichia coli Diarrhea AN - 17802796; 6160874 AB - We conducted a nested case-control study in 397 rural Egyptian children <36 months of age to assess the correlation between serum levels of antibodies against toxin and colonization factors (CFs) and the risk of homologous enterotoxigenic Escherichia coli (ETEC) diarrhea. Active case detection was performed via semiweekly home visits, and blood was obtained at 3-month intervals. After each serosurvey, case subjects were selected from children experiencing a CF antigen (CFA)/I-, CFA/II-, CFA/IV-, or heat-labile enterotoxin (LT)-ETEC diarrheal episode during the subsequent 3 months. Up to 5 control subjects per case subject were selected from children who did not experience an ETEC diarrheal episode during the corresponding interval. Serum titers of immunoglobulin G antibodies against CFA/I, coli surface antigen (CS) 3, CS6, and LT were measured by enzyme-linked immunosorbant assay. The distribution of serum titers of LT, CS3, and CS6 antibodies did not differ between the case and control subjects. For children <18 months of age, serum titers of CFA/I antibody were inversely related to the risk of CFA/I-ETEC diarrhea; reciprocal serum titers of CFA/I antibody greater than or equal to 76 were associated with a 77% reduction in the odds of CFA/I-ETEC diarrhea. Induction of reciprocal serum titers of antibodies against CFA/I within or above the 76-186 range should be further evaluated as a predictor for assessment of the ability of candidate vaccines to protect against CFA/I-ETEC diarrhea. JF - Journal of Infectious Diseases AU - Rao, M R AU - Wierzba, T F AU - Savarino, S J AU - Abu-Elyazeed, R AU - El-Ghoreb, N AU - Hall, E R AU - Naficy, A AU - Abdel-Messih, I AU - Frenck, RW Jr AU - Svennerholm, A-M AU - Clemens, J D AD - Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, Bethesda, MD, USA Y1 - 2005/02/15/ PY - 2005 DA - 2005 Feb 15 SP - 562 EP - 570 VL - 191 IS - 4 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts B: Bacteriology KW - Serum levels KW - Blood KW - Diarrhea KW - surface antigens KW - Immunoglobulin G KW - Escherichia coli KW - Vaccines KW - Children KW - Toxins KW - Colonization factor KW - heat-labile enterotoxin KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17802796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serologic+Correlates+of+Protection+against+Enterotoxigenic+Escherichia+coli+Diarrhea&rft.au=Rao%2C+M+R%3BWierzba%2C+T+F%3BSavarino%2C+S+J%3BAbu-Elyazeed%2C+R%3BEl-Ghoreb%2C+N%3BHall%2C+E+R%3BNaficy%2C+A%3BAbdel-Messih%2C+I%3BFrenck%2C+RW+Jr%3BSvennerholm%2C+A-M%3BClemens%2C+J+D&rft.aulast=Rao&rft.aufirst=M&rft.date=2005-02-15&rft.volume=191&rft.issue=4&rft.spage=562&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 - Escherichia coli; Diarrhea; Children; Serum levels; Colonization factor; Blood; heat-labile enterotoxin; Vaccines; Toxins; surface antigens; Immunoglobulin G ER - TY - JOUR T1 - DLC-1, a Rho GTPase-activating protein with tumor suppressor function, is essential for embryonic development. AN - 67426838; 15710412 AB - DLC-1 (deleted in liver cancer 1) is a Rho GTPase-activating protein that is able to inhibit cell growth and suppress tumorigenesis. We have used homologous recombination to inactivate the mouse DLC-1 gene (Arhgap7). Mice heterozygous for the targeted allele were phenotypically normal, but homozygous mutant embryos did not survive beyond 10.5 days post coitum. Histological analysis revealed that DLC-1-/- embryos had defects in the neural tube, brain, heart, and placenta. Cultured fibroblasts from DLC-1-deficient embryos displayed alterations in the organization of actin filaments and focal adhesions. JF - FEBS letters AU - Durkin, Marian E AU - Avner, Miriam R AU - Huh, Chang-Goo AU - Yuan, Bao-Zhu AU - Thorgeirsson, Snorri S AU - Popescu, Nicholas C AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, MD 20892, USA. marian_durkin@nih.gov Y1 - 2005/02/14/ PY - 2005 DA - 2005 Feb 14 SP - 1191 EP - 1196 VL - 579 IS - 5 SN - 0014-5793, 0014-5793 KW - DLC-1 (deleted in liver cancer) protein, mouse KW - 0 KW - GTPase-Activating Proteins KW - RNA, Messenger KW - Tumor Suppressor Proteins KW - Index Medicus KW - Animals KW - Cytoskeleton -- metabolism KW - Transcription, Genetic -- genetics KW - Mice KW - RNA, Messenger -- genetics KW - Fibroblasts KW - Gene Deletion KW - Mice, Knockout KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Heterozygote KW - Cytoskeleton -- pathology KW - Mutation -- genetics KW - Cytoskeleton -- genetics KW - Gene Expression Regulation, Developmental KW - Tumor Suppressor Proteins -- deficiency KW - GTPase-Activating Proteins -- genetics KW - GTPase-Activating Proteins -- metabolism KW - Embryo, Mammalian -- embryology KW - GTPase-Activating Proteins -- deficiency KW - Tumor Suppressor Proteins -- metabolism KW - Tumor Suppressor Proteins -- genetics KW - Embryo, Mammalian -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67426838?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=DLC-1%2C+a+Rho+GTPase-activating+protein+with+tumor+suppressor+function%2C+is+essential+for+embryonic+development.&rft.au=Durkin%2C+Marian+E%3BAvner%2C+Miriam+R%3BHuh%2C+Chang-Goo%3BYuan%2C+Bao-Zhu%3BThorgeirsson%2C+Snorri+S%3BPopescu%2C+Nicholas+C&rft.aulast=Durkin&rft.aufirst=Marian&rft.date=2005-02-14&rft.volume=579&rft.issue=5&rft.spage=1191&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 - 2005-04-05 N1 - Date created - 2005-02-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Psychopathology associated with drinking and alcohol use disorders in the college and general adult populations. AN - 67370889; 15664715 AB - This paper examines the associations between past-year drinking status and the prevalence of 15 different past-year anxiety, mood and personality disorders, using a large (n = 43,093) nationally representative sample of the U.S. population. The prevalence of these disorders and their associations with drinking are compared for college students 18-29 years of age, other youth 18-29 years of age, and adults 30 years of age and older. After adjusting for sociodemographic characteristics and past-year tobacco and illicit drug use, only drinkers with alcohol dependence experienced an excess risk of a mood or anxiety disorder among college students 18-29 years of age, OR = 2.4. In contrast, the excess risk of any mood or anxiety disorder associated with drinking status among non-college youth varied from an OR of 1.8 for non-binge drinkers to 4.7 for drinkers with alcohol dependence. Among persons 30 years of age and older, the degree of excess risk was slightly lower but still higher than those for college students, OR = 1.5-3.8. Similarly, the excess odds of any personality disorder associated with drinking varied from 1.6 to 5.0 for the younger, non-college group and from 1.5 to 3.8 for the older adults, with no significant effect observed among college students. Factors that may help explain the weaker association of psychopathology and drinking in the college population include selectivity and greater availability of social and treatment resources that serve as alternatives to self-medicating the symptoms of psychological distress with alcohol. JF - Drug and alcohol dependence AU - Dawson, Deborah A AU - Grant, Bridget F AU - Stinson, Frederick S AU - Chou, Patricia S AD - U.S. Department of Health and Human Services, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, NIAAA/DBE, Bethesda, MD 20892-7003, USA. ddawson@wqillco.niaaa.nih.gov Y1 - 2005/02/14/ PY - 2005 DA - 2005 Feb 14 SP - 139 EP - 150 VL - 77 IS - 2 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Humans KW - Adult KW - Psychopathology KW - Adolescent KW - Male KW - Female KW - Prevalence KW - Students -- psychology KW - Alcoholism -- epidemiology KW - Mental Disorders -- epidemiology KW - Alcohol Drinking -- psychology KW - Mental Disorders -- psychology KW - Mental Disorders -- etiology KW - Universities KW - Alcohol Drinking -- epidemiology KW - Alcoholism -- psychology KW - Alcoholism -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67370889?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Psychopathology+associated+with+drinking+and+alcohol+use+disorders+in+the+college+and+general+adult+populations.&rft.au=Dawson%2C+Deborah+A%3BGrant%2C+Bridget+F%3BStinson%2C+Frederick+S%3BChou%2C+Patricia+S&rft.aulast=Dawson&rft.aufirst=Deborah&rft.date=2005-02-14&rft.volume=77&rft.issue=2&rft.spage=139&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 - 2005-06-28 N1 - Date created - 2005-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A region in the seven-transmembrane domain of the human Ca2+ receptor critical for response to Ca2+. AN - 67407185; 15591042 AB - Of 12 naturally occurring, activating mutations in the seven-transmembrane (7TM) domain of the human Ca2+ receptor (CaR) identified previously in subjects with autosomal dominant hypocalcemia (ADH), five appear at the junction of TM helices 6 and 7 between residue Ile819 and Glu837. After identifying a sixth activating mutation in this region, V836L, in an ADH patient, we studied the remaining residues in this region to determine whether they are potential sites for activating mutations. Alanine-scanning mutagenesis revealed five additional residues in this region that when substituted by alanine led to CaR activation. We also found that, whereas E837A did not activate the receptor, E837D and E837K mutations did. Thus, region Ile819-Glu837 of the 7TM domain represents a "hot spot" for naturally occurring, activating mutations of the receptor, and most of the residues in this region apparently maintain the 7TM domain in its inactive configuration. Unique among the residues in this region, Pro823, which is highly conserved in family 3 of the G protein-coupled receptors, when mutated to either alanine or glycine, despite good expression severely impaired CaR activation by Ca2+. Both the P823A mutation and NPS 2143, a negative allosteric modulator that acts on the 7TM through a critical interaction with Glu837, blocked activation of the CaR by various ADH mutations. These results suggest that the 7TM domain region Ile819-Glu837 plays a key role in CaR activation by Ca2+. The implications of our finding that NPS 2143 corrects the molecular defect of ADH mutations for treatment of this disease are also discussed. JF - The Journal of biological chemistry AU - Hu, Jianxin AU - McLarnon, Stuart J AU - Mora, Stefano AU - Jiang, Jiankang AU - Thomas, Craig AU - Jacobson, Kenneth A AU - Spiegel, Allen M AD - Molecular Pathophysiology Section, NIDCD, National Institutes of Health, Bethesda, Maryland 20892, USA. jianxinh@intra.niddk.nih.gov Y1 - 2005/02/11/ PY - 2005 DA - 2005 Feb 11 SP - 5113 EP - 5120 VL - 280 IS - 6 SN - 0021-9258, 0021-9258 KW - Ions KW - 0 KW - Phosphatidylinositols KW - Receptors, Calcium-Sensing KW - Isoleucine KW - 04Y7590D77 KW - Glutamine KW - 0RH81L854J KW - Proline KW - 9DLQ4CIU6V KW - Alanine KW - OF5P57N2ZX KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Phosphatidylinositols -- chemistry KW - Proline -- chemistry KW - Immunoblotting KW - Protein Structure, Secondary KW - Dose-Response Relationship, Drug KW - Electrophoresis, Polyacrylamide Gel KW - Humans KW - Alanine -- chemistry KW - Protein Binding KW - Hydrolysis KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - Glutamine -- chemistry KW - Cell Membrane -- metabolism KW - Protein Structure, Tertiary KW - Allosteric Site KW - Mutation KW - Cell Line KW - Isoleucine -- chemistry KW - Calcium -- metabolism KW - Receptors, Calcium-Sensing -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67407185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=A+region+in+the+seven-transmembrane+domain+of+the+human+Ca2%2B+receptor+critical+for+response+to+Ca2%2B.&rft.au=Hu%2C+Jianxin%3BMcLarnon%2C+Stuart+J%3BMora%2C+Stefano%3BJiang%2C+Jiankang%3BThomas%2C+Craig%3BJacobson%2C+Kenneth+A%3BSpiegel%2C+Allen+M&rft.aulast=Hu&rft.aufirst=Jianxin&rft.date=2005-02-11&rft.volume=280&rft.issue=6&rft.spage=5113&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 - 2005-04-05 N1 - Date created - 2005-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epigenetic silencing of the human nucleotide excision repair gene, hHR23B, in interleukin-6-responsive multiple myeloma KAS-6/1 cells. AN - 67406179; 15550378 AB - During tumorigenesis, selective proliferative advantage in certain cell subsets is associated with accumulation of multiple genetic alterations. For instance, multiple myeloma is characterized by frequent karyotypic instability at the earliest stage, progressing to extreme genetic abnormalities as the disease progresses. These successive genetic alterations can be attributed, in part, to defects in DNA repair pathways, perhaps based on epigenetic gene silencing of proteins involved in DNA damage repair. Here we report epigenetic hypermethylation of the hHR23B gene, a key component of the nucleotide excision repair in response to DNA damage, in interleukin-6 (IL-6)-responsive myeloma KAS-6/1 cells. This hypermethylation was significantly abated by Zebularine, a potent demethylating agent, with a consequent increase in the hHR23B mRNA level. Subsequent removal of this drug and supplementation with IL-6 in the culture medium re-established DNA hypermethylation of the hHR23B gene and silencing of mRNA expression levels. The inclination of DNA to be remethylated, at least within the hHR23B gene promoter region, reflects an epigenetic driving force by the cytogenetic/tumorigenic status of KAS-6/1 myeloma. The IL-6 response of KAS-6/1 myeloma also raises a question of whether the proneoplastic growth factor, such as IL-6, supports the epigenetic silencing of important DNA repair genes via promoter hypermethylation during the development of multiple myeloma. JF - The Journal of biological chemistry AU - Peng, Benjamin AU - Hodge, David R AU - Thomas, Suneetha Betsy AU - Cherry, James M AU - Munroe, David J AU - Pompeia, Celine AU - Xiao, Weihua AU - Farrar, William L AD - Cytokine Molecular Mechanisms Section, Laboratory of Molecular Immunoregulation, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA. Y1 - 2005/02/11/ PY - 2005 DA - 2005 Feb 11 SP - 4182 EP - 4187 VL - 280 IS - 6 SN - 0021-9258, 0021-9258 KW - Culture Media KW - 0 KW - DNA, Complementary KW - DNA-Binding Proteins KW - Interleukin-6 KW - Pyrimidine Nucleosides KW - RAD23B protein, human KW - RNA, Messenger KW - Sulfites KW - RAD23A protein, human KW - 156533-33-4 KW - Cytidine KW - 5CSZ8459RP KW - pyrimidin-2-one beta-ribofuranoside KW - 7A9Y5SX0GY KW - Cytosine KW - 8J337D1HZY KW - DNA KW - 9007-49-2 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Karyotyping KW - Ultraviolet Rays KW - DNA Damage KW - Gene Silencing KW - Humans KW - Pyrimidine Nucleosides -- pharmacology KW - Transcription, Genetic KW - Culture Media -- pharmacology KW - Gene Expression Regulation, Neoplastic KW - Promoter Regions, Genetic KW - DNA Methylation KW - Down-Regulation KW - Genes, Reporter KW - Molecular Sequence Data KW - Gene Expression Regulation KW - Plasmids -- metabolism KW - DNA Repair KW - Sulfites -- pharmacology KW - Cytosine -- chemistry KW - DNA -- metabolism KW - Cell Line, Tumor KW - Dose-Response Relationship, Radiation KW - Reverse Transcriptase Polymerase Chain Reaction KW - Cytidine -- analogs & derivatives KW - Base Sequence KW - RNA, Messenger -- metabolism KW - DNA, Complementary -- metabolism KW - CpG Islands KW - Kinetics KW - Interleukin-6 -- metabolism KW - Multiple Myeloma -- metabolism KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67406179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Epigenetic+silencing+of+the+human+nucleotide+excision+repair+gene%2C+hHR23B%2C+in+interleukin-6-responsive+multiple+myeloma+KAS-6%2F1+cells.&rft.au=Peng%2C+Benjamin%3BHodge%2C+David+R%3BThomas%2C+Suneetha+Betsy%3BCherry%2C+James+M%3BMunroe%2C+David+J%3BPompeia%2C+Celine%3BXiao%2C+Weihua%3BFarrar%2C+William+L&rft.aulast=Peng&rft.aufirst=Benjamin&rft.date=2005-02-11&rft.volume=280&rft.issue=6&rft.spage=4182&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 - 2005-04-05 N1 - Date created - 2005-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel Heterocyclic Trans Olefin Analogues of N-{4-[4-(2,3-Dichlorophenyl) piperazin-1-yl]butyl}arylcarboxamides as Selective Probes with High Affinity for the Dopamine D3 Receptor AN - 19382094; 7149639 AB - Dopamine D3 receptor subtypes have been hypothesized to play a pivotal role in modulating the reinforcing and drug-seeking effects induced by cocaine. However, definitive pharmacological investigations have been hampered by the lack of highly D3 receptor selective compounds that can be used in vivo. To address this problem, the potent and D3-receptor-selective antagonist NGB 2904 (1, 9H-fluorene-2-carboxylic acid {4-[(2,3-dichlorophenyl)-piperazin-1-yl]-butyl}-amide, K sub(i) (hD3) = 2.0 nM, K sub(i) (hD2 sub(L)) = 112 nM, D2/D3 selectivity ratio of 56) was chosen as a lead structure for chemical modification in an attempt to reduce its high lipophilicity (c log D = 6.94) while optimizing D3 receptor binding affinity and D2/D3 selectivity. A series of >30 novel analogues were synthesized, and their binding affinities were evaluated in competition binding assays in HEK 293 cells transfected with either D2 sub(L), D3, or D4 human dopamine receptors using the high affinity, selective D2-like receptor antagonist super(125)I-IABN. Structural diversity in the aryl amide end of the molecule was found to have a major influence on (sub)nanomolar D3 receptor affinity and D2/D3 selectivity, which was optimized using a more rigid trans-butcnyl linker between the aryl amide and the piperazine. Several analogues demonstrated superior D3 receptor binding affinities and selectivities as compared to the parent ligand. Compound 29 (N-{4-[4-(2,3-dichloropheny the most promising pharmacological profile (K sub(i) (hD3) = 0.7 nM, K sub(i) (hD2 sub(L)) = 93.3 nM, D2/D3 selectivity ratio of 133). In addition, this ligand inhibited quinpirole stimulation of mitogenesis at human dopamine D3 receptors transfected into Chinese hamster ovary (CHO) cells, with an EC sub(50) value of 3.0 nM. Compound 29 was a nearly 5 times more potent antagonist at the D3 receptor than 1 (EC sub(50) = 14.4 nM). Moreover, a decrease in c log D value of similar to 2 orders of magnitude was determined for this novel D3-receptor-preferring ligand, compared to 1. In summary, chemical modification of 1 has resulted in compounds with high affinity and selectivity for D3 receptors. The most promising candidate, compound 29, is currently being evaluated in animal models of cocaine abuse and will provide an important tool with which to elucidate the role of D3 receptors in drug reinforcement in vivo. JF - Journal of Medicinal Chemistry AU - Grundt, P AU - Carlson, EE AU - Cao, J AU - Bennett, C J AU - McElveen, E AU - Taylor, M AU - Luedtke, R R AU - Newman, AH AD - Medicinal Chemistry Section, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA Y1 - 2005/02/10/ PY - 2005 DA - 2005 Feb 10 SP - 839 EP - 848 VL - 48 IS - 3 SN - 0022-2623, 0022-2623 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Dopamine D3 receptors KW - Probes KW - piperazine KW - Animal models KW - quinpirole KW - Drug development KW - Drug abuse KW - Dopamine D4 receptors KW - Cocaine KW - amides KW - Chemical modification KW - N3 11008:Neurochemistry KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19382094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Medicinal+Chemistry&rft.atitle=Novel+Heterocyclic+Trans+Olefin+Analogues+of+N-%7B4-%5B4-%282%2C3-Dichlorophenyl%29+piperazin-1-yl%5Dbutyl%7Darylcarboxamides+as+Selective+Probes+with+High+Affinity+for+the+Dopamine+D3+Receptor&rft.au=Grundt%2C+P%3BCarlson%2C+EE%3BCao%2C+J%3BBennett%2C+C+J%3BMcElveen%2C+E%3BTaylor%2C+M%3BLuedtke%2C+R+R%3BNewman%2C+AH&rft.aulast=Grundt&rft.aufirst=P&rft.date=2005-02-10&rft.volume=48&rft.issue=3&rft.spage=839&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medicinal+Chemistry&rft.issn=00222623&rft_id=info:doi/10.1021%2Fjm049465g LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dopamine D3 receptors; Chemical modification; amides; Cocaine; Drug abuse; Drug development; Dopamine D4 receptors; Animal models; quinpirole; piperazine; Probes DO - http://dx.doi.org/10.1021/jm049465g ER - TY - JOUR T1 - Design and Synthesis of Conformationally Constrained Grb2 SH2 Domain Binding Peptides Employing alpha -Methylphenylalanyl Based Phosphotyrosyl Mimetics AN - 19380673; 7149636 AB - Previous work has shown that incorporation of either 1-aminocyclohexanecarboxylic acid (Ac sub(6)c) or alpha -methyl-p-phosphonophenylalanine (( alpha -Me)Ppp) in the phosphotyrosyl (pTyr) C-proximal position (pY + 1 residue) of Grb2 SH2 domain binding peptides confers high affinity. The tetralin-based (S)-2-amino-6-phosphonotetralin-2-carboxylic acid (Atc(6-PO sub(3)H sub(2))) simultaneously presents structural features of both ( alpha -Me)Ppp and Ac sub(6)c residues. The current study compares the affinity of this tetralin hybrid Atc(6-PO sub(3)H sub(2)) versus Ac sub(6)c and ( alpha -Me)Ppp residues when incorporated into the pY + 1 position of a high-affinity Grb2 SH2 domain binding tripeptide platform. The highest binding affinity (K sub(D) = 14.8 nM) was exhibited by the ( alpha -Me)Ppp-containing parent, with the corresponding Ac sub(6)c-containing peptide being nearly 2-fold less potent (K sub(D) = 23.8 nM). The lower K sub(D) value was attributable primarily to a 50% increase in off-rate. Replacement of the Ac sub(6)c residue with the tetralin-based hybrid resulted in a further 4-fold decrease in binding affhity (K sub(D) = 97.8 nM), which was the result of a further 6-fold increase in off-rate, offset by an approximate 45% increase in on-rate. Therefore, by incorporation of the key structural components found in ( alpha -Me)Ppp into the Ac sub(6)c residue, the tetralin hybrid does enhance binding on-rate. However, net binding affinity is decreased due to an associated increase in binding off-rate. Alternatively, global conformational constraint of an ( alpha -Me)Ppp-containing peptide by beta -macrocyclization did result in pronounced elevation of binding affinity, which was achieved primarily through a decrease in the binding off-rate. Mathematical fitting using a simple model that assumed a single binding site yielded an effective K sub(D) of 2.28 nM. However this did not closely approximate the data obtained. Rather, use of a complex model that assumed two binding sites resulted in a very close fit of data and provided K sub(D) values of 97 pM and 72 nM for the separate sites, respectively. Therefore, although local conformational constraint in the pY + 1 residue proved to be deleterious, global conformational constraint through beta -macrocyclization achieved higher affinity. JF - Journal of Medicinal Chemistry AU - Oishi, S AU - Karki, R G AU - Kang, S-U AU - Wang, X AU - Worthy, K M AU - Bindu, L K AU - Nicklaus, M C AU - Fisher, R J AU - Burke, TR Jr AD - Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA Y1 - 2005/02/10/ PY - 2005 DA - 2005 Feb 10 SP - 764 EP - 772 VL - 48 IS - 3 SN - 0022-2623, 0022-2623 KW - Biotechnology and Bioengineering Abstracts KW - Grb2 protein KW - Mathematical models KW - Hybrids KW - tetralin KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19380673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Medicinal+Chemistry&rft.atitle=Design+and+Synthesis+of+Conformationally+Constrained+Grb2+SH2+Domain+Binding+Peptides+Employing+alpha+-Methylphenylalanyl+Based+Phosphotyrosyl+Mimetics&rft.au=Oishi%2C+S%3BKarki%2C+R+G%3BKang%2C+S-U%3BWang%2C+X%3BWorthy%2C+K+M%3BBindu%2C+L+K%3BNicklaus%2C+M+C%3BFisher%2C+R+J%3BBurke%2C+TR+Jr&rft.aulast=Oishi&rft.aufirst=S&rft.date=2005-02-10&rft.volume=48&rft.issue=3&rft.spage=764&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medicinal+Chemistry&rft.issn=00222623&rft_id=info:doi/10.1021%2Fjm0492709 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hybrids; Grb2 protein; tetralin; Mathematical models DO - http://dx.doi.org/10.1021/jm0492709 ER - TY - JOUR T1 - Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys. AN - 67419233; 15684066 AB - Excitotoxic lesion studies have confirmed that the rhinal cortex is essential for visual recognition ability in monkeys. To evaluate the mnemonic role of cholinergic inputs to this cortical region, we compared the visual recognition performance of monkeys given rhinal cortex infusions of a selective cholinergic immunotoxin, ME20.4-SAP, with the performance of monkeys given control infusions into this same tissue. The immunotoxin, which leads to selective cholinergic deafferentation of the infused cortex, yielded recognition deficits of the same magnitude as those produced by excitotoxic lesions of this region, providing the most direct demonstration to date that cholinergic activation of the rhinal cortex is essential for storing the representations of new visual stimuli and thereby enabling their later recognition. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Turchi, Janita AU - Saunders, Richard C AU - Mishkin, Mortimer AD - Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Building 49, Room 1B80, Bethesda, MD 20892, USA. turchij@mail.nih.gov Y1 - 2005/02/08/ PY - 2005 DA - 2005 Feb 08 SP - 2158 EP - 2161 VL - 102 IS - 6 SN - 0027-8424, 0027-8424 KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Animals KW - Humans KW - Macaca mulatta KW - Behavior -- physiology KW - Male KW - Recognition (Psychology) -- physiology KW - Entorhinal Cortex -- pathology KW - Acetylcholine -- metabolism KW - Entorhinal Cortex -- physiology KW - Entorhinal Cortex -- anatomy & histology KW - Afferent Pathways -- anatomy & histology KW - Memory -- physiology KW - Pattern Recognition, Visual -- physiology KW - Afferent Pathways -- metabolism KW - Afferent Pathways -- surgery UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67419233?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Effects+of+cholinergic+deafferentation+of+the+rhinal+cortex+on+visual+recognition+memory+in+monkeys.&rft.au=Turchi%2C+Janita%3BSaunders%2C+Richard+C%3BMishkin%2C+Mortimer&rft.aulast=Turchi&rft.aufirst=Janita&rft.date=2005-02-08&rft.volume=102&rft.issue=6&rft.spage=2158&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 - 2005-04-22 N1 - Date created - 2005-02-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neuron. 2003 Jun 19;38(6):987-96 [12818183] Psychopharmacology (Berl). 1997 Nov;134(1):95-106 [9399372] Neurol Res. 1979;1(2):203-9 [95356] J Comp Neurol. 1983 Feb 20;214(2):170-97 [6841683] Eur J Neurosci. 2001 Mar;13(6):1228-38 [11285020] Neuroreport. 2001 Jul 3;12(9):1913-7 [11435922] Cereb Cortex. 2002 Jul;12(7):729-36 [12050084] Brain Res Bull. 1985 Sep;15(3):307-14 [2413969] Behav Neural Biol. 1986 Jan;45(1):81-7 [3954717] Brain Res. 1986 Mar 5;367(1-2):301-8 [3516304] J Histochem Cytochem. 1986 Nov;34(11):1431-8 [2430009] Psychopharmacology (Berl). 1987;92(3):292-300 [3114781] Brain. 1988 Jun;111 ( Pt 3):695-718 [3382917] Brain Res. 1988 Oct 25;463(1):133-9 [3196902] Behav Neural Biol. 1991 Jan;55(1):61-7 [1996948] Exp Brain Res. 1991;86(1):18-26 [1756788] Brain Res. 1991 Oct 18;562(1):149-53 [1666014] Trends Neurosci. 1991 Nov;14(11):494-501 [1726766] J Neurosci. 1993 Jun;13(6):2430-51 [8501516] J Comp Neurol. 1999 May 24;408(1):11-22 [10331577] J Neurosci. 1993 Dec;13(12):5418-32 [8254384] J Neurosci. 1994 Jan;14(1):167-86 [8283232] J Neurosci. 1994 Mar;14(3 Pt 1):1271-89 [8120624] Brain Res. 1994 Nov 14;663(2):277-86 [7874512] Pharmacol Biochem Behav. 1996 Feb;53(2):277-83 [8808132] Neuroreport. 1996 Sep 2;7(13):2231-5 [8930995] Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12667-9 [9356507] Neurosci Lett. 2004 Feb 19;356(3):191-4 [15036627] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cerebrovascular perfusion in marijuana users during a month of monitored abstinence. AN - 67414425; 15699380 AB - To determine possible effects of prolonged marijuana use on the cerebrovascular system during a month of monitored abstinence and to assess how the intensity of current use might have influenced cerebrovascular perfusion in these marijuana users. The authors recorded blood flow velocity in the anterior and middle cerebral arteries using transcranial Doppler sonography in three groups of marijuana users who differed in the intensity of recent use (light: n = 11; moderate: n = 23; and heavy: n = 20) and in control subjects (n = 18) to assess the nature and duration of any potential abnormalities. Blood flow velocity was recorded within 3 days of admission and 28 to 30 days of monitored abstinence on an inpatient research unit in order to evaluate subacute effects of the drug and any abstinence-generated changes. Pulsatility index, a measure of cerebrovascular resistance, and systolic velocity were significantly increased in the marijuana users vs control subjects. These increases persisted in the heavy marijuana users after a month of monitored abstinence. Chronic marijuana use is associated with increased cerebrovascular resistance through changes mediated, in part, in blood vessels or in the brain parenchyma. These findings might provide a partial explanation for the cognitive deficits observed in a similar group of marijuana users. JF - Neurology AU - Herning, Ronald I AU - Better, Warren E AU - Tate, Kimberly AU - Cadet, Jean L AD - Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, National Institutes of Health, PO Box 5180, Baltimore, MD 21224, USA. rherning@intra.nida.nih.gov Y1 - 2005/02/08/ PY - 2005 DA - 2005 Feb 08 SP - 488 EP - 493 VL - 64 IS - 3 KW - Abridged Index Medicus KW - Index Medicus KW - Hemodynamics -- drug effects KW - Severity of Illness Index KW - Tobacco Use Disorder -- physiopathology KW - Blood Flow Velocity KW - Humans KW - Ultrasonography, Doppler, Transcranial KW - Vascular Resistance -- drug effects KW - Smoking -- physiopathology KW - Antisocial Personality Disorder -- complications KW - Adult KW - Alcohol Drinking -- physiopathology KW - Inpatients KW - Adolescent KW - Tobacco Use Disorder -- complications KW - Time Factors KW - Female KW - Male KW - Antisocial Personality Disorder -- physiopathology KW - Substance Withdrawal Syndrome -- physiopathology KW - Marijuana Abuse -- complications KW - Cerebrovascular Circulation -- drug effects KW - Cerebral Arteries -- physiopathology KW - Cannabis -- adverse effects KW - Marijuana Smoking -- physiopathology KW - Marijuana Abuse -- physiopathology KW - Cerebral Arteries -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67414425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cerebrovascular+perfusion+in+marijuana+users+during+a+month+of+monitored+abstinence.&rft.au=Herning%2C+Ronald+I%3BBetter%2C+Warren+E%3BTate%2C+Kimberly%3BCadet%2C+Jean+L&rft.aulast=Herning&rft.aufirst=Ronald&rft.date=2005-02-08&rft.volume=64&rft.issue=3&rft.spage=488&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 - 2005-09-19 N1 - Date created - 2005-02-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Neurology. 2005 Oct 11;65(7):1145; author reply 1145 [16217086] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In the quest for stable rescuing mutants of p53: computational mutagenesis of flexible loop L1. AN - 67394279; 15683227 AB - p53 is a protein with marginal stability. Its transcriptional functions are often inactivated by single missense mutations, shown to be associated with half of all human cancers. Here, we aim to design stable functional p53 mutants. We target loop L1, one of the most mobile structural motifs in the p53 core domain (p53C). Specifically, we selected Ser116 in the middle of loop L1 and mutated it to 14 other amino acids. All resulting mutants were subjected to molecular dynamics simulations, revealing a wide spectrum of stabilities. Among these, mutant S116M displayed a remarkable stability, with a structural deviation comparable to that of the experimental quadruple mutant M133L/V203A/N239Y/N268D that is thermodynamically more stable than that of the wild type by 2.6 kcal/mol. Structural analysis showed that the high stability of the S116M mutant was indeed due to the preservation of the p53C loop L1 conformation and the reduction of mobility in that region. The differential stabilities conferred by the single mutations are rationalized based on the geometries and chemical properties of the side chains introduced into this site. Linearity (i.e., nonbranched), moderate size, and balanced hydrophobic and hydrophilic properties of the side chain are crucial to the stabilizing effect of the residue substitutions. JF - Biochemistry AU - Pan, Yongping AU - Ma, Buyong AU - Venkataraghavan, R Babu AU - Levine, Arnold J AU - Nussinov, Ruth AD - Basic Research Program, SAIC-Frederick, Incorporated, Laboratory of Experimental and Computational Biology, NCI-Frederick, Frederick, Maryland 21702, USA. Y1 - 2005/02/08/ PY - 2005 DA - 2005 Feb 08 SP - 1423 EP - 1432 VL - 44 IS - 5 SN - 0006-2960, 0006-2960 KW - Neoplasm Proteins KW - 0 KW - Tumor Suppressor Protein p53 KW - Serine KW - 452VLY9402 KW - Proline KW - 9DLQ4CIU6V KW - Methionine KW - AE28F7PNPL KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Proline -- genetics KW - Methionine -- genetics KW - Amino Acid Substitution -- genetics KW - Humans KW - Cysteine -- genetics KW - Computational Biology -- methods KW - Protein Structure, Secondary -- genetics KW - Hydrogen Bonding KW - Serine -- genetics KW - Protein Conformation KW - Mutagenesis, Site-Directed KW - Computer Simulation KW - Thermodynamics KW - Models, Molecular KW - Neoplasm Proteins -- genetics KW - Tumor Suppressor Protein p53 -- chemistry KW - Neoplasm Proteins -- chemistry KW - Tumor Suppressor Protein p53 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67394279?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+the+quest+for+stable+rescuing+mutants+of+p53%3A+computational+mutagenesis+of+flexible+loop+L1.&rft.au=Pan%2C+Yongping%3BMa%2C+Buyong%3BVenkataraghavan%2C+R+Babu%3BLevine%2C+Arnold+J%3BNussinov%2C+Ruth&rft.aulast=Pan&rft.aufirst=Yongping&rft.date=2005-02-08&rft.volume=44&rft.issue=5&rft.spage=1423&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-07 N1 - Date created - 2005-02-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Portraits of a Y-family DNA polymerase. AN - 67392539; 15680965 AB - Members of the Y-family of DNA polymerases catalyze template-dependent DNA synthesis but share no sequence homology with other known DNA polymerases. Y-family polymerases exhibit high error rates and low processivity when copying normal DNA but are able to synthesize DNA opposite damaged templates. In the past three years, much has been learned about this family of polymerases including determination of more than a dozen crystal structures with various substrates. In this short review, I will summarize the biochemical properties and structural features of Y-family DNA polymerases. JF - FEBS letters 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. Wei.Yang@nih.gov Y1 - 2005/02/07/ PY - 2005 DA - 2005 Feb 07 SP - 868 EP - 872 VL - 579 IS - 4 SN - 0014-5793, 0014-5793 KW - Archaeal Proteins KW - 0 KW - Pyrimidine Dimers KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - DNA KW - 9007-49-2 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Molecular Structure KW - Base Pairing -- drug effects KW - Pyrimidine Dimers -- metabolism KW - DNA Damage KW - DNA -- metabolism KW - Archaea -- enzymology KW - Crystallography KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- pharmacology KW - Protein Conformation KW - DNA -- drug effects KW - Binding Sites KW - DNA-Directed DNA Polymerase -- physiology KW - Archaeal Proteins -- physiology KW - Archaeal Proteins -- chemistry KW - DNA-Directed DNA Polymerase -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67392539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Portraits+of+a+Y-family+DNA+polymerase.&rft.au=Yang%2C+Wei&rft.aulast=Yang&rft.aufirst=Wei&rft.date=2005-02-07&rft.volume=579&rft.issue=4&rft.spage=868&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 - 2005-03-10 N1 - Date created - 2005-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An integrated model of Plasmodium falciparum dynamics AN - 20931079; 8246764 AB - The within-host and between-host dynamics of malaria are linked in myriad ways, but most obviously by gametocytes, the parasite blood forms transmissible from human to mosquito. Gametocyte dynamics depend on those of non-transmissible blood forms, which stimulate immune responses, impeding transmission as well as within-host parasite densities. These dynamics can, in turn, influence antigenic diversity and recombination between genetically distinct parasites. Here, we embed a differential-equation model of parasite-immune system interactions within each of the individual humans represented in a discrete-event model of Plasmodium falciparum transmission, and examine the effects of human population turnover, parasite antigenic diversity, recombination, and gametocyte production on the dynamics of malaria. Our results indicate that the local persistence of P. falciparum increases with turnover in the human population and antigenic diversity in the parasite, particularly in combination, and that antigenic diversity arising from meiotic recombination in the parasite has complex differential effects on the persistence of founder and progeny genotypes. We also find that reductions in the duration of individual human infectivity to mosquitoes, even if universal, produce population-level effects only if near-absolute, and that, in competition, the persistence and prevalence of parasite genotypes with gametocyte production concordant with data exceed those of genotypes with higher gametocyte production. This new, integrated approach provides a framework for investigating relationships between pathogen dynamics within an individual host and pathogen dynamics within interacting host and vector populations. JF - Journal of Theoretical Biology AU - McKenzie, F E AU - Bossert, W H AD - Division of Engineering and Applied Sciences, Harvard University, 33 Oxford Street, Cambridge, MA 02138, USA, mckenzel@mail.nih.gov Y1 - 2005/02/07/ PY - 2005 DA - 2005 Feb 07 SP - 411 EP - 426 PB - Elsevier Science, P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl] VL - 232 IS - 3 SN - 0022-5193, 0022-5193 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Genetics Abstracts; Ecology Abstracts; ASFA 3: Aquatic Pollution & Environmental Quality; ASFA 1: Biological Sciences & Living Resources; Immunology Abstracts KW - Parasites KW - Human diseases KW - Malaria KW - Hosts KW - Genotypes KW - Models KW - Public health KW - Disease transmission KW - Recombination KW - Competition KW - Gametocytes KW - Vectors KW - Plasmodium falciparum KW - Pathogens KW - Blood KW - Infectivity KW - Meiosis KW - Progeny KW - K 03350:Immunology KW - G 07800:Plants and Algae KW - D 04030:Models, Methods, Remote Sensing KW - Q1 08484:Species interactions: parasites and diseases KW - F 06910:Microorganisms & Parasites KW - Q5 08524:Public health, medicines, dangerous organisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20931079?accountid=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+Theoretical+Biology&rft.atitle=An+integrated+model+of+Plasmodium+falciparum+dynamics&rft.au=McKenzie%2C+F+E%3BBossert%2C+W+H&rft.aulast=McKenzie&rft.aufirst=F&rft.date=2005-02-07&rft.volume=232&rft.issue=3&rft.spage=411&rft.isbn=&rft.btitle=&rft.title=Journal+of+Theoretical+Biology&rft.issn=00225193&rft_id=info:doi/10.1016%2Fj.jtbi.2004.08.021 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-07-01 N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Recombination; Parasites; Human diseases; Malaria; Pathogens; Genotypes; Hosts; Disease transmission; Public health; Gametocytes; Vectors; Models; Blood; Infectivity; Meiosis; Progeny; Competition; Plasmodium falciparum DO - http://dx.doi.org/10.1016/j.jtbi.2004.08.021 ER - TY - JOUR T1 - Transmitted mutational events induced in mouse germ cells following acrylamide or glycidamide exposure AN - 17815465; 6198011 AB - An increase in the germ line mutation rate in humans will result in an increase in the incidence of genetically determined diseases in subsequent generations. Thus, it is important to identify those agents that are mutagenic in mammalian germ cells. Acrylamide is water soluble, absorbed and distributed in the body, chemically reactive with nucleophilic sites, and there are known sources of human exposure. Here we review all seven published studies that assessed the effectiveness of acrylamide or its active metabolite, glycidamide, in inducing transmitted reciprocal translocations or gene mutations in the mouse. Major conclusions were (a) acrylamide is mutagenic in spermatozoa and spermatid stages of the male germ line; (b) in these spermatogenic stages acrylamide is mainly or exclusively a clastogen; (c) per unit dose, i.p. exposure is more effective than dermal exposure; and (d) per unit dose, glycidamide is more effective than acrylamide. Since stem cell spermatogonia persist and may accumulate mutations throughout the reproductive life of males, assessment of induced mutations in this germ cell stage is critical for the assessment of genetic risk associated with exposure to a mutagen. The two specific-locus mutation experiments which studied the stem cell spermatogonial stage yielded conflicting results. This discrepancy should be resolved. Finally, it is noted that no experiments have studied the mutagenic potential of acrylamide to increase the frequency of transmitted mutational events following exposure in the female germ line. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Favor, J AU - Shelby, MD AD - NTP-CERHR, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA, favor@gsf.de Y1 - 2005/02/07/ PY - 2005 DA - 2005 Feb 07 SP - 21 EP - 30 VL - 580 IS - 1-2 SN - 1383-5718, 1383-5718 KW - glycidamide KW - mice KW - Genetics Abstracts; Toxicology Abstracts KW - Skin KW - Point mutation KW - Germ cells KW - Metabolites KW - Sperm KW - Mutation rates KW - Mutagenesis KW - Stem cells KW - Acrylamide KW - Spermatids KW - Reviews KW - Translocations KW - Spermatogonia KW - X 24222:Analytical procedures KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17815465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=Transmitted+mutational+events+induced+in+mouse+germ+cells+following+acrylamide+or+glycidamide+exposure&rft.au=Favor%2C+J%3BShelby%2C+MD&rft.aulast=Favor&rft.aufirst=J&rft.date=2005-02-07&rft.volume=580&rft.issue=1-2&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&rft_id=info:doi/10.1016%2Fj.mrgentox.2004.09.010 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Acrylamide; Germ cells; Stem cells; Translocations; Sperm; Spermatogonia; Skin; Reviews; Metabolites; Point mutation; Spermatids; Mutation rates; Mutagenesis DO - http://dx.doi.org/10.1016/j.mrgentox.2004.09.010 ER - TY - JOUR T1 - Novel CAR-mediated mechanism for synergistic activation of two distinct elements within the human cytochrome P450 2B6 gene in HepG2 cells. AN - 67405425; 15563456 AB - The constitutive active receptor (CAR) regulates the induction of the cytochrome P450 2B6 (CYP2B6) gene by phenobarbital-type inducers, such as 1,4 bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) via the distal phenobarbital-responsive enhancer module (PBREM, at -1732/-1685 bp). Activation of the PBREM by TCPOBOP generated a 10-fold induction of CYP2B6 mRNA in HepG2 cells stably expressing mouse CAR (Ym17). Co-treatment with the protein phosphatase inhibitor okadaic acid (OA) synergistically increased this induction over 100-fold without directly activating CAR or the PBREM. Although OA synergy required the presence of PBREM, deletion assays delineated the OA-responsive activity to a proximal 24-bp (-256/-233) sequence (OARE) in the CYP2B6 promoter. CAR did not directly bind to the OARE in electrophoretic mobility shift assays. However, both DNA affinity and chromatin immunoprecipitation assays showed a significant increase in CAR association with the OARE after co-treatment with TCPOBOP and OA, indicating the indirect binding of CAR to the OARE. The two cis-acting elements, the distal PBREM and the proximal OARE, within the chromatin structure are both regulated by CAR in response to TCPOBOP and OA, respectively, to maximally induce the CYP2B6 promoter. This functional interaction between the two sites expands the current understanding of the mechanism of CAR-mediated inducible transcription. JF - The Journal of biological chemistry AU - Swales, Karen AU - Kakizaki, Satoru AU - Yamamoto, Yukio AU - Inoue, Kaoru AU - Kobayashi, Kaoru AU - Negishi, Masahiko AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2005/02/04/ PY - 2005 DA - 2005 Feb 04 SP - 3458 EP - 3466 VL - 280 IS - 5 SN - 0021-9258, 0021-9258 KW - Enzyme Inhibitors KW - 0 KW - Pyridines KW - RNA, Messenger KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - constitutive androstane receptor KW - Okadaic Acid KW - 1W21G5Q4N2 KW - 1,4-bis(2-(3,5-dichloropyridyloxy))benzene KW - 76150-91-9 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2B6 protein, human KW - Cytochrome P-450 CYP2B6 KW - Oxidoreductases, N-Demethylating KW - EC 1.5.- KW - Index Medicus KW - Liver Neoplasms KW - RNA, Messenger -- metabolism KW - Carcinoma, Hepatocellular KW - Humans KW - Okadaic Acid -- pharmacology KW - Transcriptional Activation -- physiology KW - Transcriptional Activation -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Protein Binding -- genetics KW - Cell Line, Tumor KW - Pyridines -- pharmacology KW - Oxidoreductases, N-Demethylating -- genetics KW - Gene Expression Regulation -- physiology KW - Transcription Factors -- metabolism KW - Receptors, Cytoplasmic and Nuclear -- metabolism KW - Response Elements -- genetics KW - Gene Expression Regulation -- drug effects KW - Response Elements -- drug effects KW - Aryl Hydrocarbon Hydroxylases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67405425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Novel+CAR-mediated+mechanism+for+synergistic+activation+of+two+distinct+elements+within+the+human+cytochrome+P450+2B6+gene+in+HepG2+cells.&rft.au=Swales%2C+Karen%3BKakizaki%2C+Satoru%3BYamamoto%2C+Yukio%3BInoue%2C+Kaoru%3BKobayashi%2C+Kaoru%3BNegishi%2C+Masahiko&rft.aulast=Swales&rft.aufirst=Karen&rft.date=2005-02-04&rft.volume=280&rft.issue=5&rft.spage=3458&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 - 2005-03-22 N1 - Date created - 2005-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ape1 abasic endonuclease activity is regulated by magnesium and potassium concentrations and is robust on alternative DNA structures. AN - 67361184; 15644200 AB - Abasic lesions are common mutagenic or cytotoxic DNA damages. Ape1 is the major human apurinic/apyrimidinic (AP) endonuclease and initiates repair of abasic sites by catalyzing strand cleavage at the lesion. I show here that Ape1 single-stranded (ss) AP site incision activity prefers 0.5 mM or 2 mM MgCl(2) and low concentrations (< or =50 mM) of KCl, whereas its double-stranded (ds) activity favors 10 mM MgCl(2) and 50 mM KCl or 2 mM MgCl(2) and 200 mM KCl. Both activities favor a pH between 7.0 and 7.5, suggesting a common catalytic mechanism. In conditions designed to mimic the intracellular environment (pH 7.2; 100 mM KCl; 1 mM MgCl(2)), Ape1 ssAP site incision activity is either about fivefold more active or approximately 20-fold less efficient than its ds activity, depending on the oligonucleotide employed. Secondary structure predictions suggest a role for the DNA conformational state in determining the effectiveness of Ape1. Ape1 complex stability in the presence of EDTA (non-incising conditions) is significantly weaker for ssDNA than dsDNA, regardless of the AP substrate. Duplexes where the AP site is positioned opposite the 3' terminus of a complementary primer strand are incised with an efficiency similar (less than twofold difference) to that of the ssAP substrate alone. Moreover, Ape1 cleaved AP sites in fork-like and bubble DNA structures with an efficiency that is identical or up to sevenfold higher than ssAP-DNA. The findings here suggest that Ape1 ssAP and dsAP endonuclease activities are regulated by sequence context and the relative concentrations of certain chemical elements in vivo, and that Ape1 incision activity occurs on complex replication, recombination, and/or transcription DNA intermediates. JF - Journal of molecular biology AU - Wilson, David M 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 - 2005/02/04/ PY - 2005 DA - 2005 Feb 04 SP - 1003 EP - 1014 VL - 345 IS - 5 SN - 0022-2836, 0022-2836 KW - DNA KW - 9007-49-2 KW - APEX1 protein, human KW - EC 4.2.99.18 KW - DNA-(Apurinic or Apyrimidinic Site) Lyase KW - Magnesium KW - I38ZP9992A KW - Potassium KW - RWP5GA015D KW - Index Medicus KW - Kinetics KW - Hydrogen-Ion Concentration KW - Humans KW - Substrate Specificity KW - DNA-(Apurinic or Apyrimidinic Site) Lyase -- metabolism KW - DNA -- metabolism KW - Magnesium -- pharmacology KW - Potassium -- pharmacology KW - DNA -- chemistry KW - DNA-(Apurinic or Apyrimidinic Site) Lyase -- chemistry KW - Nucleic Acid Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67361184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Ape1+abasic+endonuclease+activity+is+regulated+by+magnesium+and+potassium+concentrations+and+is+robust+on+alternative+DNA+structures.&rft.au=Wilson%2C+David+M&rft.aulast=Wilson&rft.aufirst=David&rft.date=2005-02-04&rft.volume=345&rft.issue=5&rft.spage=1003&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 - 2005-02-15 N1 - Date created - 2005-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional analysis of the Drosophila Rad51 gene (spn-A) in repair of DNA damage and meiotic chromosome segregation. AN - 67342145; 15590331 AB - Rad51 is a crucial enzyme in DNA repair, mediating the strand invasion and strand exchange steps of homologous recombination (HR). Mutations in the Drosophila Rad51 gene (spn-A) disrupt somatic as well as meiotic double-strand break (DSB) repair, similar to fungal Rad51 genes. However, the sterility of spn-A mutant females prevented a thorough analysis of the role of Rad51 in meiosis. In this study, we generated transgenic animals that express spn-A dsRNA under control of an inducible promoter, and examined the effects of inhibiting expression of spn-A on DNA repair, meiotic recombination and meiotic chromosome pairing and segregation. We found that depletion of spn-A mRNA had no effect on the viability of non-mutagen-treated transgenic animals but greatly reduced the survival of larvae that were exposed to the radiomimetic drug MMS, in agreement with the MMS and X-ray sensitivity of spn-A mutant animals. We also found that increases in dose of spn-A gene enhanced larval resistance to MMS exposure, suggesting that at high damage levels, Rad51 protein levels may be limiting for DNA repair. spn-A RNAi strongly stimulated X-X nondisjunction and decreased recombination along the X in female meiosis, consistent with a requirement of Rad51 in meiotic recombination. However, neither RNAi directed against the spn-A mRNA nor homozygosity for a spn-A null mutation had any effect on male fertility or on X-Y segregation in male meiosis, indicating that Rad51 likely plays no role in male meiotic chromosome pairing. Our results support a central role for Rad51 in HR in both somatic and meiotic DSB repair, but indicate that Rad51 in Drosophila is dispensable for meiotic chromosome pairing. Our results also provide the first demonstration that RNAi can be used to inhibit the functions of meiotic genes in Drosophila. JF - DNA repair AU - Yoo, Siuk AU - McKee, Bruce D AD - Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2005/02/03/ PY - 2005 DA - 2005 Feb 03 SP - 231 EP - 242 VL - 4 IS - 2 SN - 1568-7864, 1568-7864 KW - DNA-Binding Proteins KW - 0 KW - Drosophila Proteins KW - RNA, Small Interfering KW - Rad51 Recombinase KW - EC 2.7.7.- KW - Rad51 protein, Drosophila KW - Index Medicus KW - Animals KW - Homozygote KW - DNA Damage KW - Larva KW - Chromosome Pairing KW - Chromosome Segregation KW - Animals, Genetically Modified KW - Crossing Over, Genetic KW - RNA, Small Interfering -- pharmacology KW - Mutation KW - Female KW - Male KW - Radiation Tolerance -- genetics KW - DNA Repair KW - Recombination, Genetic KW - Meiosis -- genetics KW - Drosophila melanogaster -- metabolism KW - Drosophila Proteins -- physiology KW - DNA-Binding Proteins -- physiology KW - Drosophila melanogaster -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67342145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+analysis+of+the+Drosophila+Rad51+gene+%28spn-A%29+in+repair+of+DNA+damage+and+meiotic+chromosome+segregation.&rft.au=Yoo%2C+Siuk%3BMcKee%2C+Bruce+D&rft.aulast=Yoo&rft.aufirst=Siuk&rft.date=2005-02-03&rft.volume=4&rft.issue=2&rft.spage=231&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 - 2005-05-05 N1 - Date created - 2004-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What's in a Name? Commentary on Szekely et al. (2005), Timed Action and Object Naming AN - 85623143; 200600600 AB - Commentary on A. Szekely et al's "Timed Action and Object Naming" (Cortex, 2005, 41, 1, 7-25) commends the design & implementation of their study & relates their findings to ongoing debate over appropriate stimuli for the elicitation of action vs object naming. In a review of recent research documenting the higher cognitive load of action naming in comparison to object naming, the paradoxical word-frequency effect observed by Szekely et al (an inverse relation between reaction speed & verb frequency vs the expected direct relation between reaction speed & noun frequency) is placed in the perspective of studies attesting the neurobehavioral complexity of action naming, effects of imageability, & effects of argument complexity; in particular, S. Collina et al (2001) found that morphological class (ie, verbs vs nouns) virtually disappeared as a factor when the number of arguments was controlled in pictorial stimuli, suggesting that the difference in argument complexity attending typical verb vs noun stimuli may account for much of the observed difference in cognitive processing load. 10 References. J. Hitchcock JF - Cortex AU - Frattali, Carol AD - Speech-Language Pathology Section, Dept Rehabilitation Medicine, WG Magnuson Clinical Center, National Instits Health, Bethesda, MD carol_frattali@nih.gov Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 3 EP - 5 VL - 41 IS - 1 SN - 0010-9452, 0010-9452 KW - Cognitive Processes (12950) KW - Naming (56135) KW - Word Frequency (97450) KW - Visual Stimulation (94700) KW - Psycholinguistics (69200) KW - Form Classes (25250) KW - Semantic Categories (76580) KW - Research Design (72950) KW - article KW - 4010: psycholinguistics; psycholinguistics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85623143?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cortex&rft.atitle=What%27s+in+a+Name%3F+Commentary+on+Szekely+et+al.+%282005%29%2C+Timed+Action+and+Object+Naming&rft.au=Frattali%2C+Carol&rft.aulast=Frattali&rft.aufirst=Carol&rft.date=2005-02-01&rft.volume=41&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Cortex&rft.issn=00109452&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2006-02-01 N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Naming (56135); Research Design (72950); Word Frequency (97450); Form Classes (25250); Semantic Categories (76580); Cognitive Processes (12950); Psycholinguistics (69200); Visual Stimulation (94700) ER - TY - JOUR T1 - Melatonin is Involved in Sex Change of the Ricefield Eel, Monopterus albus Zuiew AN - 853476148; 14055457 AB - The ricefield eel (Monopterus albus Zuiew), a burrowing eel-like synbranchoid teleost, undergoes a natural sex change from female to male during its life history. Since the teleost pineal gland and its melatoninergic output have been suggested as regulators in seasonal reproduction and sexual maturation in many fish species, it is reasonable to postulate that melatonin may play important roles in the ricefield eel's sex-change process. This hypothesis was tested by examining secretional characteristics and reproductive effects of melatonin in the ricefield eel. Results indicate that serum melatonin (mainly secreted from the pineal complex, retinae and gastrointestinal tract) is involved in sex change of this species. It seems that, within a reproductive cycle, relatively lower mid-night serum melatonin (MNSM) levels are necessary for natural spawning, but relatively higher MNSM levels after spawning permit initiation of the sex-change process. A putative model is presented to clarify the involvement of melatonin in natural sex change of the ricefield eel, although the precise mechanisms are still under further investigation. JF - Reviews in Fish Biology and Fisheries AU - Shi, Qiong AD - Institute of Aquatic Economical Animals, School of Life Sciences, Zhongshan University, Guangzhou, 510275, PRC, shiq@mail.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 23 EP - 36 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 15 IS - 1-2 SN - 0960-3166, 0960-3166 KW - ASFA 1: Biological Sciences & Living Resources; Ecology Abstracts; Oceanic Abstracts KW - Retinas KW - Pineal organ KW - Catadromous species KW - Spawning KW - Teleostei KW - Models KW - Reproductive status KW - Life history KW - Serum KW - Reproductive cycle KW - Sexual maturity KW - Melatonin KW - Reproduction KW - Pineal gland KW - Gastrointestinal tract KW - Monopterus albus KW - Sex KW - O 5080:Legal/Governmental KW - D 04040:Ecosystem and Ecology Studies KW - Q1 08582:Fish culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/853476148?accountid=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=Reviews+in+Fish+Biology+and+Fisheries&rft.atitle=Melatonin+is+Involved+in+Sex+Change+of+the+Ricefield+Eel%2C+Monopterus+albus+Zuiew&rft.au=Shi%2C+Qiong&rft.aulast=Shi&rft.aufirst=Qiong&rft.date=2005-02-01&rft.volume=15&rft.issue=1-2&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Reviews+in+Fish+Biology+and+Fisheries&rft.issn=09603166&rft_id=info:doi/10.1007%2Fs11160-005-7848-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-02-01 N1 - Last updated - 2014-05-02 N1 - SubjectsTermNotLitGenreText - Retinas; Serum; Pineal organ; Sexual maturity; Reproductive cycle; Catadromous species; Sex; Reproductive status; Life history; Reproduction; Melatonin; Gastrointestinal tract; Spawning; Pineal gland; Models; Monopterus albus; Teleostei DO - http://dx.doi.org/10.1007/s11160-005-7848-2 ER - TY - JOUR T1 - The immunomodulator vasoactive intestinal peptide (VIP) does not affect experimental autoimmune uveitis (EAU) in B10.RIII mice. AN - 67702095; 15804764 AB - Vasoactive intestinal peptide (VIP) exhibits immunomodulatory activities both in vivo and in vitro, including efficient inhibition of murine experimental arthritis. In this study, we investigated the effects of VIP treatment on the induction of experimental autoimmune uveoretinitis (EAU). EAU was induced in B10.RIII mice by immunization with interphotoreceptor retinoid-binding protein (IRBP) using routine methods, but without treatment with pertussis toxin (PTX). VIP was injected i.p. at different doses into mice on alternate days. Mice were tested by conventional methods for ocular inflammation, antibody levels, lymphocyte proliferation, and cytokine release by cultured lymphocytes. Treatment with VIP, at different doses, had essentially no effect on the development of EAU or antibody production in the B10.RIII mice. The treatment did have variable effects on the low interferon-gamma production by lymphocytes of these mice. Unlike its inhibitory effect in the experimental arthritis system, VIP did not modulate the development of EAU in B10.RIII mice. JF - Ocular immunology and inflammation AU - Chen, Jun AU - Vistica, Barbara AU - Wiggert, Barbara AU - Chan, Chi-Chao AU - Gery, Igal AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1857, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 13 EP - 17 VL - 13 IS - 1 SN - 0927-3948, 0927-3948 KW - Cytokines KW - 0 KW - Eye Proteins KW - Immunoglobulin G KW - Neuroprotective Agents KW - Retinol-Binding Proteins KW - interstitial retinol-binding protein KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Index Medicus KW - Lymphocyte Activation KW - Injections, Intraperitoneal KW - Immunoglobulin G -- blood KW - Animals KW - Antibody Formation KW - Mice KW - Cytokines -- metabolism KW - B-Lymphocytes -- immunology KW - T-Lymphocytes -- immunology KW - Female KW - Retinitis -- drug therapy KW - Retinitis -- immunology KW - Autoimmune Diseases -- drug therapy KW - Autoimmune Diseases -- chemically induced KW - Vasoactive Intestinal Peptide -- therapeutic use KW - Uveitis -- immunology KW - Neuroprotective Agents -- therapeutic use KW - Retinitis -- chemically induced KW - Uveitis -- drug therapy KW - Uveitis -- chemically induced KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67702095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ocular+immunology+and+inflammation&rft.atitle=The+immunomodulator+vasoactive+intestinal+peptide+%28VIP%29+does+not+affect+experimental+autoimmune+uveitis+%28EAU%29+in+B10.RIII+mice.&rft.au=Chen%2C+Jun%3BVistica%2C+Barbara%3BWiggert%2C+Barbara%3BChan%2C+Chi-Chao%3BGery%2C+Igal&rft.aulast=Chen&rft.aufirst=Jun&rft.date=2005-02-01&rft.volume=13&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Ocular+immunology+and+inflammation&rft.issn=09273948&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-09 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Neuroadaptive mechanisms form development of psychological dependence on volatile organic solvents]. AN - 67555064; 15796064 AB - Abuse of volatile organic solvents among youth remains a major social problem. Organic solvents are cheap and relatively easy to obtain, so they carry the risk of becoming a so-called "gateway drug" for users. Most research regarding organic solvents has until now focused on their neurotoxicity, specifically examining the mechanism of neuron death in terms of the involvement of substances such as nerve growth factor. However, systems to assess psychological dependence on volatile organic solvents that take into account the mechanism involved in the development of this dependence have not been established due to the difficulty of creating animal models. The conditioned place preference procedure, which can easily assess whether psychological dependence has been formed, has been phased in in recent years, and dependence assessment systems have been established for drug inhalation. There have also been new research developments regarding dependence on volatile organic solvents. The importance of mesolimbic dopamine neurons has been indicated in the expression of CNS stimulant action and the development of psychological dependence on drugs such as stimulants, cocaine, and heroin, which are typical abused drugs. It has recently become apparent that the increase in dopamine release in the nucleus accumbens accompanying activation of mesolimbic dopamine neurons, as has conventionally been proposed, is important to the expression of CNS stimulant action and the formation of psychological dependence in response to inhalation of toluene, a volatile organic solvent. Furthermore, research with regard to organic solvents' site of action is also proceeding based on studies using molecular biological techniques. Research regarding toluene is progressing, and the importance of receptors that gate ion channels such as N-methyl-D-aspartate (NMDA) and y-aminobutyric acid (GABA)A receptors as candidates for toluene's site of action has been indicated. Clarification of organic solvents' mechanism for the development of psychological dependence is expected to progress, thanks to analysis focusing on such new sites of action. JF - Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology AU - Funada, Masahiko AU - Sato, Mio AU - Zhou, Xiaohua AU - Kanai, Hiroko AU - Wada, Kiyoshi AD - Division of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3 Kohnodai, Ichikawa, 272-0827, Japan. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 1 EP - 9 VL - 25 IS - 1 SN - 1340-2544, 1340-2544 KW - Biogenic Monoamines KW - 0 KW - Solvents KW - Toluene KW - 3FPU23BG52 KW - Index Medicus KW - Animals KW - Toluene -- pharmacology KW - Biogenic Monoamines -- physiology KW - Neurons -- physiology KW - Substance-Related Disorders -- physiopathology KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67555064?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+shinkei+seishin+yakurigaku+zasshi+%3D+Japanese+journal+of+psychopharmacology&rft.atitle=%5BNeuroadaptive+mechanisms+form+development+of+psychological+dependence+on+volatile+organic+solvents%5D.&rft.au=Funada%2C+Masahiko%3BSato%2C+Mio%3BZhou%2C+Xiaohua%3BKanai%2C+Hiroko%3BWada%2C+Kiyoshi&rft.aulast=Funada&rft.aufirst=Masahiko&rft.date=2005-02-01&rft.volume=25&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Nihon+shinkei+seishin+yakurigaku+zasshi+%3D+Japanese+journal+of+psychopharmacology&rft.issn=13402544&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-29 N1 - Date created - 2005-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential effects of forskolin on tyrosine hydroxylase gene transcription in identified brainstem catecholaminergic neuronal subtypes in organotypic culture. AN - 67546289; 15787695 AB - The regulation of gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, was studied in brainstem noradrenergic nuclei, locus coeruleus (LC), A2 and A1, in vitro. Several novel experimental approaches employed in this study included: (i) the development of a slice-explant model in which these brainstem nuclei maintained a high survival of the noradrenergic neurons, an organotypic topology and the coexpression of two identifying markers in addition to TH, i.e. norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2); (ii) quantitative analysis of TH transcription in these nuclei was made using a labelled intronic probe to measure TH heteronuclear RNA (hnRNA) and (iii) the use of tetrodotoxin in the media to eliminate spontaneous neural activity in these nuclei, thereby providing a basal state as the starting point for the study of TH transcription under various pharmacological perturbations. In the presence of TTX, the adenylcyclase stimulator, forskolin, produced a 155% increase in LC, a 130% increase in A1, and a 220% increase in A2 in TH hnRNA as compared to control nuclei. This effect of forskolin was abolished in the LC and A1 by the PKA inhibitor, H89 (5 microm), but not by the MAP kinase pathway (MEK) inhibitor, PD98059 (75 microm). In contrast, the robust increase in TH transcription produced by forskolin in A2 neurons, was completely inhibited by PD98059, and only partially inhibited by H89, showing that induced TH transcription is mediated by different kinase pathways in specific central noradrenergic neuronal subtypes. JF - The European journal of neuroscience AU - Rusnak, Milan AU - Gainer, Harold AD - Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 889 EP - 898 VL - 21 IS - 4 SN - 0953-816X, 0953-816X KW - Catecholamines KW - 0 KW - GABA Antagonists KW - Isoquinolines KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Norepinephrine Plasma Membrane Transport Proteins KW - Protein Kinase Inhibitors KW - Slc18a2 protein, rat KW - Slc6a2 protein, rat KW - Sulfonamides KW - Symporters KW - Vesicular Biogenic Amine Transport Proteins KW - Vesicular Monoamine Transport Proteins KW - Colforsin KW - 1F7A44V6OU KW - Tetrodotoxin KW - 4368-28-9 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide KW - M876330O56 KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Animals KW - Drug Interactions KW - Protein Kinase Inhibitors -- pharmacology KW - Symporters -- metabolism KW - Immunohistochemistry -- methods KW - GABA Antagonists -- pharmacology KW - Rats KW - Animals, Newborn KW - Isoquinolines -- pharmacology KW - Rats, Sprague-Dawley KW - Sulfonamides -- pharmacology KW - Cell Count -- methods KW - In Situ Hybridization -- methods KW - In Vitro Techniques KW - Tetrodotoxin -- pharmacology KW - Membrane Transport Proteins -- metabolism KW - Membrane Glycoproteins -- metabolism KW - Catecholamines -- genetics KW - Tyrosine 3-Monooxygenase -- metabolism KW - Colforsin -- pharmacology KW - Neurons -- metabolism KW - Catecholamines -- metabolism KW - Tyrosine 3-Monooxygenase -- genetics KW - Neurons -- drug effects KW - Brain Stem -- cytology KW - Gene Expression Regulation, Developmental -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67546289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+European+journal+of+neuroscience&rft.atitle=Differential+effects+of+forskolin+on+tyrosine+hydroxylase+gene+transcription+in+identified+brainstem+catecholaminergic+neuronal+subtypes+in+organotypic+culture.&rft.au=Rusnak%2C+Milan%3BGainer%2C+Harold&rft.aulast=Rusnak&rft.aufirst=Milan&rft.date=2005-02-01&rft.volume=21&rft.issue=4&rft.spage=889&rft.isbn=&rft.btitle=&rft.title=The+European+journal+of+neuroscience&rft.issn=0953816X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-16 N1 - Date created - 2005-03-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug interactions in the management of HIV infection. AN - 67503329; 15757420 AB - The availability of antiretroviral therapy has significantly reduced the morbidity and mortality of HIV infection. In addition, improved treatment of opportunistic infections and comorbidities common to patients with HIV is further prolonging the lives of patients. Improvement in the treatment of HIV has led to a significant increase in the number of medications which caregivers are able to utilise to manage HIV/AIDS. Antiretroviral medications, as well as many of the drugs used in the management of opportunistic infections and primary care (e.g., macrolide antibiotics, azole antifungals, cholesterol-lowering medications), are particularly prone to drug interactions. The interpretation of clinically significant interactions is complicated by the rate at which new information on drug metabolism and transport is becoming available. Management of drug interactions in HIV is further confounded by conflicting study results and differences between documented and theoretical inter-actions. The mechanisms and significance of interactions involving antiretrovirals, drugs used for opportunistic infections, and other medications commonly used in HIV patients will be reviewed. JF - Expert opinion on pharmacotherapy AU - Robertson, Sarah M AU - Penzak, Scott R AU - Pau, Alice K AD - National Institutes of Health, Clinical Pharmacokinetics Research Laboratory, Clinical Center Pharmacy Department, Bethesda, Maryland 20892, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 233 EP - 253 VL - 6 IS - 2 KW - Anti-HIV Agents KW - 0 KW - Cytochrome P-450 Enzyme Inhibitors KW - HIV Protease Inhibitors KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - CYP3A protein, human KW - EC 1.14.14.1 KW - Cytochrome P-450 CYP3A KW - Index Medicus KW - Humans KW - Disease Management KW - Cytochrome P-450 Enzyme System -- metabolism KW - Anti-HIV Agents -- pharmacokinetics KW - Anti-HIV Agents -- therapeutic use KW - HIV Infections -- drug therapy KW - HIV Protease Inhibitors -- pharmacokinetics KW - HIV Infections -- enzymology KW - HIV-1 -- enzymology KW - HIV Protease Inhibitors -- therapeutic use KW - HIV-1 -- drug effects KW - Drug Interactions -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67503329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Drug+interactions+in+the+management+of+HIV+infection.&rft.au=Robertson%2C+Sarah+M%3BPenzak%2C+Scott+R%3BPau%2C+Alice+K&rft.aulast=Robertson&rft.aufirst=Sarah&rft.date=2005-02-01&rft.volume=6&rft.issue=2&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Expert+opinion+on+pharmacotherapy&rft.issn=1744-7666&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-04-06 N1 - Date created - 2005-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidemiology and natural history of hepatocellular carcinoma. AN - 67500841; 15757802 AB - Hepatocellular carcinoma (HCC) is a major contributor to cancer incidence and mortality. There is a wide variation, however, in the global distribution of HCC. Eighty percent of the burden is borne by countries in Asia and sub-Saharan Africa. In most high-risk countries, principal risk factors include infection with hepatitis B virus and dietary exposure to aflatoxin B(1). In contrast, hepatitis C virus and alcohol consumption are more important risk factors in low-risk countries. In recent years, the incidence of HCC has decreased in some high-risk countries and increased in some low-risk countries. Reasons for both trends are not completely understood, but are likely related to public health efforts in Asia and the increase in hepatitis C virus infection in low-risk countries. Vaccination programs against hepatitis B virus will likely decrease the HCC rate even further in decades to come. JF - Best practice & research. Clinical gastroenterology AU - McGlynn, Katherine A AU - London, W Thomas AD - HREB/DCEG, National Cancer Institute, EPS-7060, 6120 Executive Boulevard, Rockville, MD 20892, USA. mcglynnk@mail.nih.gov Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 3 EP - 23 VL - 19 IS - 1 SN - 1521-6918, 1521-6918 KW - Aflatoxins KW - 0 KW - Index Medicus KW - Hepatitis B -- complications KW - Hepatitis C -- complications KW - Risk Factors KW - Humans KW - Food Contamination KW - Incidence KW - Liver Cirrhosis -- complications KW - Genetic Predisposition to Disease KW - Chemoprevention KW - Alcohol Drinking KW - Aflatoxins -- adverse effects KW - Global Health KW - Carcinoma, Hepatocellular -- virology KW - Liver Neoplasms -- therapy KW - Carcinoma, Hepatocellular -- genetics KW - Carcinoma, Hepatocellular -- therapy KW - Liver Neoplasms -- virology KW - Liver Neoplasms -- epidemiology KW - Carcinoma, Hepatocellular -- epidemiology KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67500841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Best+practice+%26+research.+Clinical+gastroenterology&rft.atitle=Epidemiology+and+natural+history+of+hepatocellular+carcinoma.&rft.au=McGlynn%2C+Katherine+A%3BLondon%2C+W+Thomas&rft.aulast=McGlynn&rft.aufirst=Katherine&rft.date=2005-02-01&rft.volume=19&rft.issue=1&rft.spage=3&rft.isbn=&rft.btitle=&rft.title=Best+practice+%26+research.+Clinical+gastroenterology&rft.issn=15216918&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-30 N1 - Date created - 2005-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevalence of hepatitis C virus infection in different population groups in southern Italy. AN - 67489710; 15750753 AB - A cross-sectional investigation was carried out between 2000 and 2002 to assess the prevalence of hepatitis C virus infection (HCV) in Naples, southern Italy. Five groups of individuals were investigated, two at low risk and three at high risk for HCV infection. Blood sample sera were collected among 5,391 individuals (4,059 men and 1,332 women): 1,972 general practitioner (GP) patients and 781 employees of the National Cancer Institute (NCI) of Naples (low-risk groups); 524 male prisoners, 1,436 intravenous drug users (IDUs) and 678 hemodialysis patients (high-risk groups). Overall HCV seropositivity rates ranged from 6.4% among employees of the NCI to 37.4% among male prisoners. HCV infection tended to generally increase with age, but in IDUs and in male prisoners the upward trend leveled off at 50 years of age. As compared to GP patients, IDUs (both sexes) and male prisoners had a nearly 6-fold increased risk of HCV infection, while HCV was nearly 3-fold more common among hemodialysis patients. Employees of NCI were at reduced risk of HCV infection, particularly women (odds ratio = 0.3). The study findings confirmed the high risk for HCV infection in IDUs and identified other population groups in southern Italy that should be offered HCV screening and counselling given the severe implications of HCV infection on health. JF - Infection AU - Montella, M AU - Crispo, A AU - Grimaldi, M AU - Angeletti, C AU - Amore, A AU - Ronga, D AU - Sabbatini, M AU - Sabbatici, M AU - Pisani, A AU - Spiteri, D AU - Serraino, D AD - Epidemiology Unit, National Cancer Institute, G. Pascale Foundation, Naples, Italy. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 9 EP - 12 VL - 33 IS - 1 SN - 0300-8126, 0300-8126 KW - Index Medicus KW - Humans KW - Aged KW - Renal Dialysis KW - Prisoners KW - Cross-Sectional Studies KW - Adult KW - Health Personnel KW - Middle Aged KW - Italy -- epidemiology KW - Adolescent KW - Female KW - Male KW - Substance Abuse, Intravenous KW - Prevalence KW - Hepatitis C -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67489710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Prevalence+of+hepatitis+C+virus+infection+in+different+population+groups+in+southern+Italy.&rft.au=Montella%2C+M%3BCrispo%2C+A%3BGrimaldi%2C+M%3BAngeletti%2C+C%3BAmore%2C+A%3BRonga%2C+D%3BSabbatini%2C+M%3BSabbatici%2C+M%3BPisani%2C+A%3BSpiteri%2C+D%3BSerraino%2C+D&rft.aulast=Montella&rft.aufirst=M&rft.date=2005-02-01&rft.volume=33&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Infection&rft.issn=03008126&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-04 N1 - Date created - 2005-03-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Infection. 2005 Apr;33(2):103 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A neoceptor approach to unraveling microscopic interactions between the human A2A adenosine receptor and its agonists. AN - 67469473; 15734651 AB - Strategically mutated neoceptors, e.g., with anionic residues in TMs 3 and 7 intended for pairing with positively charged amine-modified nucleosides, were derived from the antiinflammatory A(2A) adenosine receptor (AR). Adenosine derivatives functionalized at the 5', 2, and N(6) positions were synthesized. The T88D mutation selectively enhanced the binding of the chain-length-optimized 5'-(2-aminoethyl)uronamide but not 5'-(2-hydroxyethyl)uronamide, suggesting a critical role of the positively charged amine. Combination of this modification with the N(6)-(2-methylbenzyl) group enhanced affinity at the Q89D- and N181D- but not the T88D-A(2A)AR. Amino groups placed near the 2- or N(6)-position only slightly affected the binding to mutant receptors. The 5'-hydrazide MRS3412 was 670- and 161-fold enhanced, in binding and functionally, respectively, at the Q89D-A(2A)AR compared to the wild-type. Thus, we identified and modeled pairs of A(2A)AR-derived neoceptor-neoligand, which are pharmacologically orthogonal with respect to the native species. JF - Chemistry & biology AU - Jacobson, Kenneth A AU - Ohno, Michihiro AU - Duong, Heng T AU - Kim, Soo-Kyung AU - Tchilibon, Susanna AU - Cesnek, Michal AU - Holý, Antonín 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 20892, USA. kajacobs@helix.nih.gov Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 237 EP - 247 VL - 12 IS - 2 SN - 1074-5521, 1074-5521 KW - Ligands KW - 0 KW - Receptor, Adenosine A2A KW - Recombinant Proteins KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Molecular Structure KW - Recombinant Proteins -- metabolism KW - Models, Molecular KW - Recombinant Proteins -- ultrastructure KW - Humans KW - Protein Conformation KW - Binding Sites KW - Adenosine -- agonists KW - Receptor, Adenosine A2A -- chemistry KW - Adenosine -- chemistry KW - Receptor, Adenosine A2A -- genetics KW - Adenosine -- chemical synthesis KW - Receptor, Adenosine A2A -- ultrastructure KW - Receptor, Adenosine A2A -- metabolism KW - Adenosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67469473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemistry+%26+biology&rft.atitle=A+neoceptor+approach+to+unraveling+microscopic+interactions+between+the+human+A2A+adenosine+receptor+and+its+agonists.&rft.au=Jacobson%2C+Kenneth+A%3BOhno%2C+Michihiro%3BDuong%2C+Heng+T%3BKim%2C+Soo-Kyung%3BTchilibon%2C+Susanna%3BCesnek%2C+Michal%3BHol%C3%BD%2C+Anton%C3%ADn%3BGao%2C+Zhan-Guo&rft.aulast=Jacobson&rft.aufirst=Kenneth&rft.date=2005-02-01&rft.volume=12&rft.issue=2&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Chemistry+%26+biology&rft.issn=10745521&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-25 N1 - Date created - 2005-02-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: FASEB J. 2000 Jul;14(10):1423-31 [10877835] J Med Chem. 1999 Sep 9;42(18):3463-77 [10479279] Biochem Pharmacol. 2000 Sep 1;60(5):661-8 [10927024] Am J Physiol Renal Physiol. 2000 Nov;279(5):F809-18 [11053040] Surgery. 2001 Mar;129(3):324-34 [11231461] Chem Biol. 2001 Mar;8(3):277-87 [11306352] Pharm Res. 2001 Apr;18(4):531-6 [11451042] J Med Chem. 2001 Nov 22;44(24):4125-36 [11708915] Pharmacol Rev. 2001 Dec;53(4):527-52 [11734617] Nature. 2001 Dec 20-27;414(6866):916-20 [11780065] Chem Biol. 2002 Jan;9(1):17-23 [11841935] J Vasc Surg. 2002 May;35(5):994-8 [12021717] J Med Chem. 2002 Jul 18;45(15):3271-9 [12109910] J Biol Chem. 2002 Aug 9;277(32):28916-22 [12034735] Biochem Pharmacol. 2003 May 15;65(10):1675-84 [12754103] Autoimmun Rev. 2002 Aug;1(4):213-9 [12848998] J Med Chem. 2003 Nov 6;46(23):4847-59 [14584936] Bioorg Med Chem. 2004 Jun 1;12(11):2995-3007 [15142558] Am J Physiol Heart Circ Physiol. 2004 Sep;287(3):H1096-103 [15130891] Med Klin. 1972 Sep 8;67(36):1138-40 [5073418] Biochem Pharmacol. 1973 Dec 1;22(23):3099-108 [4202581] Anal Biochem. 1976 May 7;72:248-54 [942051] J Comput Aided Mol Des. 1990 Mar;4(1):1-105 [2197373] J Med Chem. 1990 Sep;33(9):2545-51 [2391695] Anal Biochem. 1990 Sep;189(2):231-4 [2177960] J Med Chem. 1994 Mar 4;37(5):636-46 [8126704] J Pharm Sci. 1994 Jan;83(1):46-53 [8138909] Eur J Pharmacol. 1996 Dec 5;316(2-3):171-9 [8982684] J Med Chem. 1997 Aug 1;40(16):2588-95 [9258366] Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):352-7 [9419379] Chem Biol. 1998 Feb;5(2):91-101 [9495830] Bioorg Med Chem Lett. 1998 Mar 17;8(6):695-8 [9871585] Science. 2000 Aug 4;289(5480):739-45 [10926528] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Useful tool to generate unidirectional deletion vectors by utilizing the star activity of BamHI in an NcoI-BamHI-XhoI cassette. AN - 67448950; 15727125 JF - BioTechniques AU - Chen, Kevin G AU - Gottesman, Michael M AD - Laboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 198 EP - 198, 200, 202, 204 VL - 38 IS - 2 SN - 0736-6205, 0736-6205 KW - ABCB5 protein, human KW - 0 KW - P-Glycoprotein KW - Deoxyribonuclease BamHI KW - EC 3.1.21.- KW - CTCGAG-specific type II deoxyribonucleases KW - EC 3.1.21.4 KW - Deoxyribonucleases, Type II Site-Specific KW - Index Medicus KW - Mutagenesis, Site-Directed -- genetics KW - Humans KW - P-Glycoprotein -- genetics KW - Deoxyribonuclease BamHI -- genetics KW - Cloning, Molecular -- methods KW - Genetic Engineering -- methods KW - Genetic Vectors -- genetics KW - Deoxyribonucleases, Type II Site-Specific -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67448950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Useful+tool+to+generate+unidirectional+deletion+vectors+by+utilizing+the+star+activity+of+BamHI+in+an+NcoI-BamHI-XhoI+cassette.&rft.au=Chen%2C+Kevin+G%3BGottesman%2C+Michael+M&rft.aulast=Chen&rft.aufirst=Kevin&rft.date=2005-02-01&rft.volume=38&rft.issue=2&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=BioTechniques&rft.issn=07366205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-31 N1 - Date created - 2005-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I trial and pharmacokinetic study of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in metastatic breast cancer. AN - 67427560; 15709195 AB - Farnesyltransferase (FTase) inhibitors, which were designed to inhibit oncogenic Ras, act synergistically with tamoxifen in preclinical breast cancer models. We studied the safety and toxicity of tipifarnib in combination with tamoxifen in metastatic breast cancer. The pharmacokinetics and pharmacodynamics of tipifarnib were also assessed. Patients with metastatic, hormone receptor-positive breast cancer were enrolled. Two cohorts of patients were treated with tipifarnib at either 200 or 300 mg p.o. twice daily for 21 of 28 days. Tamoxifen (20 mg once daily) was started after 1 week of tipifarnib monotherapy to perform pharmacokinetics and FTase inhibition levels in peripheral blood mononuclear cells with tipifarnib alone and with tipifarnib and tamoxifen. A total of 12 heavily pretreated patients with prior progression on hormonal therapy were enrolled. Minimal toxicity was observed at the 200-mg dose level of tipifarnib. At the 300-mg dose, all six patients required dose reduction of tipifarnib due to toxicities that included grade 2 nausea, rash, and fatigue and grade 3 diarrhea and neutropenia. Tipifarnib pharmacokinetic and pharmacodynamic variables were similar in the presence and absence of tamoxifen. Average FTase inhibition was 42% at 200 mg and 54% at 300 mg in peripheral blood mononuclear cells. Of the 12 patients treated, there were two partial responses and one stable disease for >6 months. Tipifarnib (200 mg twice daily for 21 of 28 days) and tamoxifen (20 mg once daily) can be given safely with minimal toxicity. Tamoxifen does not have a significant effect on tipifarnib pharmacokinetics. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Lebowitz, Peter F AU - Eng-Wong, Jennifer AU - Widemann, Brigitte C AU - Balis, Frank M AU - Jayaprakash, Nalini AU - Chow, Catherine AU - Clark, Geoff AU - Gantz, Susan B AU - Venzon, David AU - Zujewski, JoAnne AD - Medical Oncology Clinical Research Unit, National Cancer Institute/NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA. peter.lebowitz@nih.gov Y1 - 2005/02/01/ PY - 2005 DA - 2005 Feb 01 SP - 1247 EP - 1252 VL - 11 IS - 3 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Quinolones KW - Tamoxifen KW - 094ZI81Y45 KW - Alkyl and Aryl Transferases KW - EC 2.5.- KW - Farnesyltranstransferase KW - EC 2.5.1.29 KW - tipifarnib KW - MAT637500A KW - Index Medicus KW - Area Under Curve KW - Dose-Response Relationship, Drug KW - Humans KW - Fatigue -- chemically induced KW - Anemia -- chemically induced KW - Aged KW - Alkyl and Aryl Transferases -- antagonists & inhibitors KW - Exanthema -- chemically induced KW - Leukocytes, Mononuclear -- enzymology KW - Adult KW - Antineoplastic Agents, Hormonal -- administration & dosage KW - Treatment Outcome KW - Neoplasm Metastasis KW - Middle Aged KW - Leukocytes, Mononuclear -- drug effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Agents, Hormonal -- therapeutic use KW - Male KW - Female KW - Alkyl and Aryl Transferases -- metabolism KW - Breast Neoplasms -- drug therapy KW - Quinolones -- adverse effects KW - Quinolones -- pharmacokinetics KW - Tamoxifen -- therapeutic use KW - Breast Neoplasms -- metabolism KW - Tamoxifen -- administration & dosage KW - Quinolones -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67427560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+phase+I+trial+and+pharmacokinetic+study+of+tipifarnib%2C+a+farnesyltransferase+inhibitor%2C+and+tamoxifen+in+metastatic+breast+cancer.&rft.au=Lebowitz%2C+Peter+F%3BEng-Wong%2C+Jennifer%3BWidemann%2C+Brigitte+C%3BBalis%2C+Frank+M%3BJayaprakash%2C+Nalini%3BChow%2C+Catherine%3BClark%2C+Geoff%3BGantz%2C+Susan+B%3BVenzon%2C+David%3BZujewski%2C+JoAnne&rft.aulast=Lebowitz&rft.aufirst=Peter&rft.date=2005-02-01&rft.volume=11&rft.issue=3&rft.spage=1247&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 - 2005-05-31 N1 - Date created - 2005-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endogenous leukemia inhibitory factor attenuates endotoxin response. AN - 67416636; 15702085 AB - Leukemia inhibitory factor (LIF) is induced in inflammation and likely plays a regulatory role. Using LIF-deficient mice (LIF-/-), we report here that endogenous LIF has a protective role in endotoxic shock and host defence. LIF-/- mice have heightened sensitivity to LPS in a LPS/D-galactosamine (D-Gal) sensitization model compared to wild-type mice (LIF+/+), enhanced thrombocytopenia and leukopenia, with increased hepatic necrosis, neutrophil sequestration in the lung and accelerated mortality. These findings correlated with 10-fold higher tumour necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6) serum levels and reduced IL-10 production in LIF-/- mice in response to LPS. Therefore, endogenous LIF attenuates the endotoxic shock response, enhances the expression of basal acute phase proteins and IL-10 production, which downregulates TNFalpha synthesis and release and thereby confers partial protection to endotoxemia. JF - Laboratory investigation; a journal of technical methods and pathology AU - Weber, Marietta A AU - Schnyder-Candrian, Silvia AU - Schnyder, Bruno AU - Quesniaux, Valerie AU - Poli, Valeria AU - Stewart, Colin L AU - Ryffel, Bernhard AD - Cancer and Developmental Biology Laboratory, NCI-FCRDC, Frederick, MD, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 276 EP - 284 VL - 85 IS - 2 SN - 0023-6837, 0023-6837 KW - Endotoxins KW - 0 KW - Interleukin-6 KW - Leukemia Inhibitory Factor KW - Lif protein, mouse KW - Lipopolysaccharides KW - RNA, Messenger KW - Serum Amyloid A Protein KW - Tumor Necrosis Factor-alpha KW - Interleukin-10 KW - 130068-27-8 KW - Galactosamine KW - 7535-00-4 KW - Index Medicus KW - Galactosamine -- pharmacology KW - Animals KW - Liver -- pathology KW - RNA, Messenger -- analysis KW - Spleen -- pathology KW - Macrophages -- physiology KW - Mice KW - Lung -- pathology KW - Mice, Inbred BALB C KW - Macrophages -- drug effects KW - Mice, Knockout KW - Galactosamine -- administration & dosage KW - Down-Regulation KW - Acute-Phase Reaction -- etiology KW - Cells, Cultured KW - Tumor Necrosis Factor-alpha -- analysis KW - Lipopolysaccharides -- toxicity KW - Tumor Necrosis Factor-alpha -- antagonists & inhibitors KW - Serum Amyloid A Protein -- analysis KW - Interleukin-10 -- blood KW - Time Factors KW - Interleukin-6 -- blood KW - Interleukin-6 -- genetics KW - Endotoxemia -- prevention & control KW - Endotoxins -- blood KW - Shock, Septic -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67416636?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Endogenous+leukemia+inhibitory+factor+attenuates+endotoxin+response.&rft.au=Weber%2C+Marietta+A%3BSchnyder-Candrian%2C+Silvia%3BSchnyder%2C+Bruno%3BQuesniaux%2C+Valerie%3BPoli%2C+Valeria%3BStewart%2C+Colin+L%3BRyffel%2C+Bernhard&rft.aulast=Weber&rft.aufirst=Marietta&rft.date=2005-02-01&rft.volume=85&rft.issue=2&rft.spage=276&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 - 2005-04-21 N1 - Date created - 2005-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased activity of cyclin-dependent kinase 5 leads to attenuation of cocaine-mediated dopamine signaling. AN - 67397061; 15665076 AB - Cocaine, a drug of abuse, increases synaptic dopamine levels in the striatum by blocking dopamine reuptake at axon terminals. Cyclin-dependent kinase 5 (Cdk5) and its activator p35, proteins involved in phosphorylation of substrates in postmitotic neurons, have been found to be up-regulated after chronic exposure to cocaine. To further examine the effects of Cdk5 and p35 induction on striatal dopamine signaling, we generated two independent transgenic mouse lines in which Cdk5 or p35 was overexpressed specifically in neurons. We report here that increased Cdk5 activity, as a result of p35 but not of Cdk5 overexpression, leads to attenuation of cocaine-mediated dopamine signaling. Increased Cdk5-mediated phosphorylation of dopamine and cAMP-regulated phosphoprotein, molecular mass 32 kDa (DARPP-32) at Thr-75, was accompanied by decreased phosphorylation of DARPP-32 at Thr-34. Increased Cdk5-mediated phosphorylation of extracellular signal-regulated kinase kinase 1 at Thr-286 was accompanied by decreased activation of extracellular signal-regulated kinase 1/2. These effects contributed to attenuation of cocaine-induced phosphorylation of cAMP response element-binding protein as well as a lesser induction of c-fos in the striatum. These results support the idea that Cdk5 activity is involved in altered gene expression after chronic exposure to cocaine and hence impacts the long-lasting changes in neuronal function underlying cocaine addiction. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Takahashi, Satoru AU - Ohshima, Toshio AU - Cho, Andrew AU - Sreenath, Taduru AU - Iadarola, Michael J AU - Pant, Harish C AU - Kim, Yong AU - Nairn, Angus C AU - Brady, Roscoe O AU - Greengard, Paul AU - Kulkarni, Ashok B AD - Functional Genomics Section, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, MD 20892, USA. Y1 - 2005/02/01/ PY - 2005 DA - 2005 Feb 01 SP - 1737 EP - 1742 VL - 102 IS - 5 SN - 0027-8424, 0027-8424 KW - RNA KW - 63231-63-0 KW - Cyclin-Dependent Kinase 5 KW - EC 2.7.11.1 KW - Cdk5 protein, mouse KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinases KW - Cocaine KW - I5Y540LHVR KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Brain -- physiology KW - Corpus Striatum -- enzymology KW - Gene Expression Regulation, Enzymologic KW - Cocaine-Related Disorders -- enzymology KW - Restriction Mapping KW - RNA -- isolation & purification KW - Spinal Cord -- physiology KW - RNA -- genetics KW - Cyclin-Dependent Kinases -- metabolism KW - Cyclin-Dependent Kinases -- genetics KW - Signal Transduction -- physiology KW - Synapses -- physiology KW - Signal Transduction -- drug effects KW - Dopamine -- physiology KW - Cocaine -- pharmacology KW - Cocaine -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67397061?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+activity+of+cyclin-dependent+kinase+5+leads+to+attenuation+of+cocaine-mediated+dopamine+signaling.&rft.au=Takahashi%2C+Satoru%3BOhshima%2C+Toshio%3BCho%2C+Andrew%3BSreenath%2C+Taduru%3BIadarola%2C+Michael+J%3BPant%2C+Harish+C%3BKim%2C+Yong%3BNairn%2C+Angus+C%3BBrady%2C+Roscoe+O%3BGreengard%2C+Paul%3BKulkarni%2C+Ashok+B&rft.aulast=Takahashi&rft.aufirst=Satoru&rft.date=2005-02-01&rft.volume=102&rft.issue=5&rft.spage=1737&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 - 2005-03-28 N1 - Date created - 2005-02-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2191-6 [14769920] J Biol Chem. 2003 Mar 21;278(12):10506-15 [12536148] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1291-5 [1825356] Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5061-5 [1647024] Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5764-8 [1631058] J Neurosci. 1992 Aug;12(8):3071-83 [1494946] Neuron. 1993 Dec;11(6):995-1006 [8274284] Neuron. 1994 Nov;13(5):1235-44 [7946359] Chem Senses. 1995 Apr;20(2):257-60 [7583020] Genomics. 1996 Jul 15;35(2):372-5 [8661152] Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11173-8 [8855328] Neuron. 1997 Jan;18(1):29-42 [9010203] Neuron. 1999 Jul;23(3):435-47 [10433257] Nature. 1999 Sep 16;401(6750):272-6 [10499584] Nat Neurosci. 2003 Nov;6(11):1208-15 [14566342] Nature. 1999 Dec 9;402(6762):669-71 [10604473] J Neurosci. 2000 Dec 1;20(23):8701-9 [11102476] J Neurosci. 2000 Dec 15;20(24):8965-71 [11124971] Mol Vis. 2000 Dec 13;6:252-60 [11134582] J Neurosci. 2001 Jan 15;21(2):550-8 [11160434] Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2764-9 [11226314] Nat Rev Neurosci. 2001 Feb;2(2):119-28 [11252991] Nature. 2001 Mar 15;410(6826):376-80 [11268215] J Biol Chem. 2001 Apr 13;276(15):11487-95 [11139572] Nat Rev Mol Cell Biol. 2001 Oct;2(10):749-59 [11584302] J Biol Chem. 2002 Jan 4;277(1):528-34 [11684694] Neuropharmacology. 2004;47 Suppl 1:14-23 [15464122] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Structural and functional analysis of the RNA transport element, a member of an extensive family present in the mouse genome. AN - 67392698; 15681436 AB - We previously identified an RNA transport element (RTE), present in a subclass of rodent intracisternal A particle retroelements (F. Nappi, R. Schneider, A. Zolotukhin, S. Smulevitch, D. Michalowski, J. Bear, B. Felber, and G. Pavlakis, J. Virol. 75:4558-4569, 2001), that is able to replace Rev-responsive element regulation in human immunodeficiency virus type 1. RTE-directed mRNA export is mediated by a still-unknown cellular factor(s), is independent of the CRM1 nuclear export receptor, and is conserved among vertebrates. Here we show that this RTE folds into an extended RNA secondary structure and thus does not resemble any known RTEs. Computer searches revealed the presence of 105 identical elements and more than 3,000 related elements which share at least 70% sequence identity with the RTE and which are found on all mouse chromosomes. These related elements are predicted to fold into RTE-like structures. Comparison of the sequences and structures revealed that the RTE and related elements can be divided into four groups. Mutagenesis of the RTE revealed that the minimal element contains four internal stem-loops, which are indispensable for function in mammalian cells. In contrast, only part of the element is essential to mediate RNA transport in microinjected Xenopus laevis oocyte nuclei. Importantly, the minimal RTE able to promote RNA transport has key structural features which are preserved in all the RTE-related elements, further supporting their functional importance. Therefore, RTE function depends on a complex secondary structure that is important for the interaction with the cellular export factor(s). JF - Journal of virology AU - Smulevitch, Sergey AU - Michalowski, Daniel AU - Zolotukhin, Andrei S AU - Schneider, Ralf AU - Bear, Jenifer AU - Roth, Patricia AU - Pavlakis, George N AU - Felber, Barbara K AD - Human Retrovirus Pathogenesis Section, NCI--Frederick, Frederick, MD 21702, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 2356 EP - 2365 VL - 79 IS - 4 SN - 0022-538X, 0022-538X KW - RNA KW - 63231-63-0 KW - Index Medicus KW - Xenopus laevis KW - Animals KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Humans KW - Molecular Sequence Data KW - Oocytes KW - Mice KW - Nucleic Acid Conformation KW - RNA Transport -- genetics KW - RNA -- chemistry KW - RNA -- analysis KW - Genome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67392698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Structural+and+functional+analysis+of+the+RNA+transport+element%2C+a+member+of+an+extensive+family+present+in+the+mouse+genome.&rft.au=Smulevitch%2C+Sergey%3BMichalowski%2C+Daniel%3BZolotukhin%2C+Andrei+S%3BSchneider%2C+Ralf%3BBear%2C+Jenifer%3BRoth%2C+Patricia%3BPavlakis%2C+George+N%3BFelber%2C+Barbara+K&rft.aulast=Smulevitch&rft.aufirst=Sergey&rft.date=2005-02-01&rft.volume=79&rft.issue=4&rft.spage=2356&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 - 2005-08-09 N1 - Date created - 2005-01-31 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AC003061; GENBANK; AY876077; AL663101; AY876079; AY876078; AL671215 N1 - SuppNotes - Cited By: J Virol. 1994 Dec;68(12):7944-52 [7966585] J Cell Biol. 1994 Mar;124(5):627-35 [7509815] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11940-4 [8524879] J Virol. 1996 Jun;70(6):3834-43 [8648719] J Virol. 1996 Sep;70(9):5998-6011 [8709222] Mol Cell Biol. 1997 Jan;17(1):135-44 [8972193] J Virol. 1997 Jan;71(1):95-101 [8985327] RNA. 1997 Feb;3(2):210-22 [9042947] J Virol. 1997 Jul;71(7):4892-903 [9188551] EMBO J. 1997 Jun 2;16(11):3256-71 [9214641] Curr Biol. 1997 Sep 1;7(9):619-28 [9285715] J Mol Biol. 1998 Jan 16;275(2):211-20 [9466904] J Virol. 1998 Apr;72(4):3407-11 [9525671] Biotechniques. 1998 Mar;24(3):462-6, 468-71 [9526659] RNA. 1998 Apr;4(4):351-64 [9630243] Mol Cell. 1998 Apr;1(5):649-59 [9660949] EMBO J. 1999 Apr 1;18(7):1953-65 [10202158] J Virol. 1999 Nov;73(11):9496-507 [10516058] Annu Rev Cell Dev Biol. 1999;15:607-60 [10611974] J Virol. 2000 Oct;74(20):9353-61 [11000203] J Virol. 2000 Oct;74(20):9507-14 [11000220] RNA. 2000 Nov;6(11):1551-64 [11105755] RNA. 2000 Dec;6(12):1762-72 [11142376] J Virol. 2001 May;75(10):4558-69 [11312326] Curr Opin Cell Biol. 2001 Jun;13(3):310-9 [11343901] J Virol. 2001 Jun;75(12):5567-75 [11356964] J Biol Chem. 2002 Feb 8;277(6):3935-42 [11724776] EMBO J. 2003 May 15;22(10):2472-83 [12743041] Nat Genet. 2004 May;36(5):534-9 [15107856] Exp Cell Res. 2004 May 15;296(1):12-20 [15120988] J Virol. 1989 Mar;63(3):1265-74 [2783738] Nature. 1989 Mar 16;338(6212):254-7 [2784194] Proc Natl Acad Sci U S A. 1989 Mar;86(5):1495-9 [2784208] J Virol. 1990 Aug;64(8):3734-41 [2196381] Genes Dev. 1990 Jun;4(6):1014-22 [2116986] J Virol. 1990 Dec;64(12):6010-7 [2243384] Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1256-60 [8108397] J Virol. 1995 Jan;69(1):141-9 [7983704] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of pulsed Doppler tissue velocity imaging for assessing systolic function of murine global heart failure. AN - 67389886; 15682052 AB - The feasibility of Doppler tissue imaging (DTI) for assessing global systolic function has not been determined in small animals, particularly at near-conscious heart rates. Therefore, we compared DTI measurements with conventional M-mode-derived fractional shortening in murine global left ventricular systolic dysfunction induced by intraperitoneal doxorubicin (Dox) injection. In all, 13 female C57BL mice received 20 mg/kg of Dox and 12 mice received saline injection (controls). DTI signals were obtained from the inferior wall through parasternal short-axis views. The heart rate was kept at near-conscious level throughout DTI measurements (approximately 500/min). Left ventricular systolic dysfunction was detectable by measurements of fractional shortening from 4 to 14 days after Dox administration. Among DTI measurements, peak systolic velocity and time to peak systolic velocity decreased from 4 to 14 days after Dox injection. Our results indicate that these new DTI measurements appear feasible to assess global left ventricular systolic dysfunction in mice. JF - Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography AU - Matoba, Satoaki AU - Hwang, Paul M AU - Nguyen, Tammy AU - Shizukuda, Yukitaka AD - Cardiovascular Branch, National Heart, Lung, and Blood Institute/NIH, Building 10/7B15, 10 Center Drive, MSC-1650, Bethesda, MD 20892, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 148 EP - 154 VL - 18 IS - 2 SN - 0894-7317, 0894-7317 KW - Antibiotics, Antineoplastic KW - 0 KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Animals KW - Myocytes, Cardiac -- drug effects KW - Reproducibility of Results KW - Blood Flow Velocity -- drug effects KW - Disease Models, Animal KW - Mice KW - Myocytes, Cardiac -- pathology KW - Mice, Inbred C57BL KW - Systole -- drug effects KW - Observer Variation KW - Stroke Volume -- drug effects KW - Female KW - Echocardiography, Doppler, Pulsed KW - Heart Failure -- chemically induced KW - Heart Failure -- diagnostic imaging KW - Ventricular Dysfunction, Left -- physiopathology KW - Ventricular Dysfunction, Left -- diagnostic imaging KW - Heart Failure -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67389886?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+Society+of+Echocardiography+%3A+official+publication+of+the+American+Society+of+Echocardiography&rft.atitle=Evaluation+of+pulsed+Doppler+tissue+velocity+imaging+for+assessing+systolic+function+of+murine+global+heart+failure.&rft.au=Matoba%2C+Satoaki%3BHwang%2C+Paul+M%3BNguyen%2C+Tammy%3BShizukuda%2C+Yukitaka&rft.aulast=Matoba&rft.aufirst=Satoaki&rft.date=2005-02-01&rft.volume=18&rft.issue=2&rft.spage=148&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Society+of+Echocardiography+%3A+official+publication+of+the+American+Society+of+Echocardiography&rft.issn=08947317&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-09-15 N1 - Date created - 2005-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucocorticoid receptor ligand binding domain is sufficient for the modulation of glucocorticoid induction properties by homologous receptors, coactivator transcription intermediary factor 2, and Ubc9. AN - 67384490; 15539428 AB - Several factors modulate the position of the dose-response curve of steroid receptor-agonist complexes and the partial agonist activity of antagonist complexes, thereby causing differential gene activation by circulating hormones and unequal gene repression during endocrine therapies with antisteroids. We now ask whether the modulatory activity of three factors (homologous receptor, coactivator transcription intermediary factor 2, and Ubc9) requires the same or different domains of glucocorticoid receptors (GRs). In all cases, we find that neither the amino terminal half of the receptor, which contains the activation function-1 activation domain, nor the DNA binding domain is required. This contrasts with the major role of activation function-1 in determining the amount of gene expression and partial agonist activity of antisteroids with most steroid receptors. However, the situation is more complicated with Ubc9, where GR N-terminal sequences prevent the actions of Ubc9, but not added GR or transcription intermediary factor 2, at low GR concentrations. Inhibition is relieved by deletion of these sequences or by replacement with the comparable region of progesterone receptors but not by overexpression of the repressive sequences. These results plus the binding of C-terminal GR sequences to the suppressive N-terminal domain implicate an intramolecular mechanism for the inhibition of Ubc9 actions at low GR concentrations. A shift from noncooperative to cooperative steroid binding at high GR concentrations suggests that conformational changes reposition the inhibitory N-terminal sequence to allow Ubc9 interaction with elements of the ligand binding domain. Collectively, these results indicate a dominant role of GR C-terminal sequences in the modulation of the dose-response curve and partial agonist activity of GR complexes. They also reveal mechanistic differences both among individual modulators and between the ability of the same factors to regulate the total amount of gene expression. JF - Molecular endocrinology (Baltimore, Md.) AU - Cho, Sehyung AU - Kagan, Benjamin L AU - Blackford, John A AU - Szapary, Daniele AU - Simons, S Stoney AD - Steriod Hormones Section, National Institute of Diabetes and Digestive and Kidney Diseases/LMCB, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 290 EP - 311 VL - 19 IS - 2 SN - 0888-8809, 0888-8809 KW - Glucocorticoids KW - 0 KW - Ligands KW - Nuclear Receptor Coactivator 2 KW - Receptors, Glucocorticoid KW - Steroids KW - Transcription Factors KW - Dexamethasone KW - 7S5I7G3JQL KW - DNA KW - 9007-49-2 KW - Sepharose KW - 9012-36-6 KW - Ubiquitin-Conjugating Enzymes KW - EC 2.3.2.23 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - ubiquitin-conjugating enzyme UBC9 KW - EC 6.3.2.- KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - COS Cells KW - Dexamethasone -- pharmacology KW - Transcription, Genetic KW - Mutagenesis, Site-Directed KW - Rats KW - Genes, Dominant KW - Gene Expression Regulation KW - Steroids -- chemistry KW - Steroids -- metabolism KW - Protein Biosynthesis KW - Plasmids -- metabolism KW - Dose-Response Relationship, Drug KW - Dimerization KW - DNA -- metabolism KW - Glutathione Transferase -- metabolism KW - Protein Binding KW - Transcriptional Activation KW - Sepharose -- chemistry KW - Blotting, Western KW - Transfection KW - Kinetics KW - Glutathione -- chemistry KW - Protein Structure, Tertiary KW - Mutation KW - Cell Line KW - Cell-Free System KW - Ubiquitin-Conjugating Enzymes -- metabolism KW - Glucocorticoids -- metabolism KW - Receptors, Glucocorticoid -- chemistry KW - Transcription Factors -- metabolism KW - Receptors, Glucocorticoid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67384490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Glucocorticoid+receptor+ligand+binding+domain+is+sufficient+for+the+modulation+of+glucocorticoid+induction+properties+by+homologous+receptors%2C+coactivator+transcription+intermediary+factor+2%2C+and+Ubc9.&rft.au=Cho%2C+Sehyung%3BKagan%2C+Benjamin+L%3BBlackford%2C+John+A%3BSzapary%2C+Daniele%3BSimons%2C+S+Stoney&rft.aulast=Cho&rft.aufirst=Sehyung&rft.date=2005-02-01&rft.volume=19&rft.issue=2&rft.spage=290&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 - 2005-06-07 N1 - Date created - 2005-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preclinical evaluation of a novel episcleral cyclosporine implant for ocular graft-versus-host disease. AN - 67381987; 15671296 AB - To develop a local drug delivery system that provides therapeutic cyclosporine levels to treat lacrimal gland graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Episcleral cyclosporine implants were manufactured with a silicone-based matrix design, and in vitro release rates were determined. Preclinical evaluation included toxicology (clinical examination, serial electroretinography, and histopathology) in normal rabbits and dogs, pharmacokinetics in normal rabbits, and pharmacodynamics in a canine model of aqueous tear deficiency and keratoconjunctivitis sicca. The cyclosporine implants showed sustained release of drug over time with in vitro assays. Histopathology showed normal ocular tissues in both dogs and rabbits 6 months after implantation. The cyclosporine implant produced lacrimal gland drug levels 1 to 2 log units higher than those reported with a variety of topical cyclosporine formulations and oral administration. The cyclosporine implant was effective in a canine model of keratoconjunctivitis sicca, with all animals able to discontinue topical cyclosporine and maintain normal Schirmer scores over a 6-month follow-up. This preclinical evaluation showed that the episcleral cyclosporine implant was safe, delivered potentially therapeutic cyclosporine levels to the lacrimal gland, and showed efficacy in a clinically relevant model of keratoconjunctivitis sicca. The episcleral cyclosporine implant shows promise in reducing the morbidity associated with lacrimal gland graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. In addition, continuous release of cyclosporine in the subconjunctival space with the episcleral implant was an effective means of delivering drug to the ocular surface and may have potential in treating other ocular inflammatory diseases. JF - Investigative ophthalmology & visual science AU - Kim, Hyuncheol AU - Csaky, Karl G AU - Gilger, Brian C AU - Dunn, James P AU - Lee, Susan S AU - Tremblay, Marcus AU - de Monasterio, Francisco AU - Tansey, Ginger AU - Yuan, Peng AU - Bungay, Peter M AU - Lutz, Robert J AU - Robinson, Michael R AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1863, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 655 EP - 662 VL - 46 IS - 2 SN - 0146-0404, 0146-0404 KW - Drug Implants KW - 0 KW - Immunosuppressive Agents KW - Cyclosporine KW - 83HN0GTJ6D KW - Index Medicus KW - Animals KW - Keratoconjunctivitis -- pathology KW - Retina -- drug effects KW - Safety KW - Keratoconjunctivitis -- drug therapy KW - Rabbits KW - Electroretinography -- drug effects KW - Biological Availability KW - Dogs KW - Drug Evaluation, Preclinical KW - Female KW - Male KW - Cyclosporine -- toxicity KW - Eye -- pathology KW - Sclera -- pathology KW - Graft vs Host Disease -- prevention & control KW - Immunosuppressive Agents -- pharmacology KW - Eye -- metabolism KW - Graft vs Host Disease -- pathology KW - Sclera -- drug effects KW - Sclera -- metabolism KW - Cyclosporine -- pharmacology KW - Immunosuppressive Agents -- toxicity KW - Cyclosporine -- pharmacokinetics KW - Immunosuppressive Agents -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67381987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Preclinical+evaluation+of+a+novel+episcleral+cyclosporine+implant+for+ocular+graft-versus-host+disease.&rft.au=Kim%2C+Hyuncheol%3BCsaky%2C+Karl+G%3BGilger%2C+Brian+C%3BDunn%2C+James+P%3BLee%2C+Susan+S%3BTremblay%2C+Marcus%3Bde+Monasterio%2C+Francisco%3BTansey%2C+Ginger%3BYuan%2C+Peng%3BBungay%2C+Peter+M%3BLutz%2C+Robert+J%3BRobinson%2C+Michael+R&rft.aulast=Kim&rft.aufirst=Hyuncheol&rft.date=2005-02-01&rft.volume=46&rft.issue=2&rft.spage=655&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 - 2005-03-11 N1 - Date created - 2005-01-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. AN - 67372770; 15655768 AB - In 2001, CDC, the National Institutes of Health, and the Infectious Diseases Society of America convened a working group to develop guidelines for therapy of human immunodeficiency virus (HIV)-associated opportunistic infections to serve as a companion to the Guidelines for Prevention of Opportunistic Infections Among HIV-Infected Persons. In recognition of unique considerations related to HIV infection among infants, children, and adolescents, a separate pediatric working group was established. Because HIV-infected women coinfected with opportunistic pathogens might be more likely to transmit these infections to their infants than women without HIV infection, guidelines for treating opportunistic pathogens among children should consider treatment of congenitally acquired infections among both HIV-exposed but uninfected children and those with HIV infection. In addition, the natural history of opportunistic infections among HIV-infected children might differ from that among adults. Compared with opportunistic infections among HIV-infected adults, which are often caused by reactivation of pathogens acquired before HIV infection when host immunity was intact, opportunistic infections among children often reflect primary acquisition of the pathogen and, among children with perinatal HIV infection, infection acquired after HIV infection has been established and begun to compromise an already immature immune system. Laboratory diagnosis of opportunistic infections can be more difficult with children. Finally, treatment recommendations should consider differences between adults and children in terms of drug pharmacokinetics, dosing, formulations, administration, and toxicities. This report focuses on treatment of opportunistic infections that are common in HIV-exposed and infected infants, children, and adolescents in the United States. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Mofenson, Lynne M AU - Oleske, James AU - Serchuck, Leslie AU - Van Dyke, Russell AU - Wilfert, Cathy AD - National Institutes of Health, Bethesda, Maryland, USA. lm65d@nih.gov Y1 - 2005/02/01/ PY - 2005 DA - 2005 Feb 01 SP - S1 EP - 84 VL - 40 Suppl 1 KW - Index Medicus KW - United States KW - HIV Seropositivity KW - Humans KW - Adult KW - Child KW - Adolescent KW - Societies, Medical KW - Communicable Diseases -- therapy KW - HIV Infections -- complications KW - Centers for Disease Control and Prevention (U.S.) KW - Communicable Diseases -- diagnosis KW - National Institutes of Health (U.S.) KW - Health Planning Guidelines KW - Communicable Diseases -- epidemiology KW - AIDS-Related Opportunistic Infections -- diagnosis KW - AIDS-Related Opportunistic Infections -- epidemiology KW - AIDS-Related Opportunistic Infections -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67372770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Treating+opportunistic+infections+among+HIV-exposed+and+infected+children%3A+recommendations+from+CDC%2C+the+National+Institutes+of+Health%2C+and+the+Infectious+Diseases+Society+of+America.&rft.au=Mofenson%2C+Lynne+M%3BOleske%2C+James%3BSerchuck%2C+Leslie%3BVan+Dyke%2C+Russell%3BWilfert%2C+Cathy&rft.aulast=Mofenson&rft.aufirst=Lynne&rft.date=2005-02-01&rft.volume=40+Suppl+1&rft.issue=&rft.spage=S1&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 - 2006-02-23 N1 - Date created - 2005-01-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Clin Infect Dis. 2006 Oct 1;43(7):951 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of neonatal exposure to diethylstilbestrol, tamoxifen, and toremifene on the BALB/c mouse mammary gland. AN - 67371912; 15470002 AB - In this study, we compared the long-term effects of neonatal exposure to diethylstilbestrol (DES, 0.0125-50 microg), tamoxifen (TAM, 0.0125-50 microg), and toremifene (TOR, 53 microg) on mammary gland development and differentiation. Allometric growth of the mammary ducts was stimulated by neonatal DES exposure (12.5 microg) and impaired by exposure to TAM (25 microg). Neonatal treatment with high doses of DES resulted in mammary ducts that displayed extensive dilatation and precocious lactogenesis in postpubertal, nulliparous females. Initiation of this precocious differentiation coincided with the absence of corpora lutea, increased levels of serum prolactin (PRL), and the induction of Prl mRNA expression within the mammary glands. Neonatal exposure to 1.25 microg TAM increased alveolar development in postpubertal, nulliparous females similar to that recorded in females treated with low doses of DES. Lower doses of TAM did not affect alveolar development, whereas branching morphogenesis and alveolar development were impaired by higher doses. Increased alveolar development in females exposed to 1.25 microg TAM was associated with elevated serum progesterone (P) and increased alveolar development in response to exogenous P. Taken together, our findings demonstrate that neonatal exposure to both DES and TAM exerts long-lasting effects on the proliferation and differentiation of the mammary glands in female BALB/c, primarily as the result of endocrine disruption. JF - Biology of reproduction AU - Hovey, Russell C AU - Asai-Sato, Mikiko AU - Warri, Anni AU - Terry-Koroma, Barbara AU - Colyn, Nira AU - Ginsburg, Erika AU - Vonderhaar, Barbara K AD - Molecular and Cellular Endocrinology Section, Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1402, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 423 EP - 435 VL - 72 IS - 2 SN - 0006-3363, 0006-3363 KW - Estrogen Antagonists KW - 0 KW - Estrogens, Non-Steroidal KW - Hormones KW - Tamoxifen KW - 094ZI81Y45 KW - RNA KW - 63231-63-0 KW - Diethylstilbestrol KW - 731DCA35BT KW - Toremifene KW - 7NFE54O27T KW - Index Medicus KW - Animals KW - Genitalia, Female -- drug effects KW - Dose-Response Relationship, Drug KW - Hormones -- blood KW - Mice KW - Mice, Inbred BALB C KW - RNA -- biosynthesis KW - Aging -- physiology KW - Lactation -- drug effects KW - Blotting, Western KW - In Situ Hybridization KW - RNA -- isolation & purification KW - Ovariectomy KW - Organ Culture Techniques KW - Immunohistochemistry KW - Female KW - RNA -- genetics KW - Genitalia, Female -- growth & development KW - Tamoxifen -- pharmacology KW - Mammary Glands, Animal -- drug effects KW - Estrogen Antagonists -- pharmacology KW - Diethylstilbestrol -- pharmacology KW - Toremifene -- pharmacology KW - Mammary Glands, Animal -- growth & development KW - Estrogens, Non-Steroidal -- pharmacology KW - Animals, Newborn -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67371912?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+neonatal+exposure+to+diethylstilbestrol%2C+tamoxifen%2C+and+toremifene+on+the+BALB%2Fc+mouse+mammary+gland.&rft.au=Hovey%2C+Russell+C%3BAsai-Sato%2C+Mikiko%3BWarri%2C+Anni%3BTerry-Koroma%2C+Barbara%3BColyn%2C+Nira%3BGinsburg%2C+Erika%3BVonderhaar%2C+Barbara+K&rft.aulast=Hovey&rft.aufirst=Russell&rft.date=2005-02-01&rft.volume=72&rft.issue=2&rft.spage=423&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 - 2005-05-24 N1 - Date created - 2005-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene expression profiling of chemically induced rat mammary gland cancer. AN - 67369352; 15528215 AB - Exposure to carcinogens through diet, the atmosphere and other means is generally regarded as influencing human cancer risk, but the impact of specific environmental carcinogens on human breast cancer incidence is still unknown. We examined whether distinct chemical carcinogens induce a unique transcriptional profile in mammary gland cancer that is characteristic of the etiologic agent. Rat mammary gland cancers (n = 34) were generated by various carcinogens, including the food-derived heterocyclic amines 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 7,12-dimethylbenz[a]anthracene, N-nitrosomethylurea and 4-aminobiphenyl. The histopathology of the carcinomas was graded using a modified Scarff-Bloom-Richardson scheme and the gene expression profiles in the carcinomas were evaluated on a 10K cDNA microarray. Unsupervised hierarchical clustering analysis revealed two major clusters of carcinomas irrespective of the carcinogenic agent that distinguished two groups with different histopathological parameters (degree of differentiation, nuclear grade, mitotic activity, epithelial cell growth pattern and necrosis). Using class comparison analysis and hierarchical clustering of all carcinomas irrespective of histopathology, gene expression profiles were further shown to be statistically differentially expressed according to the carcinogenic agent. These findings indicate that the transcriptional program in carcinomas is unique to the etiologic agent and can be observed among a diverse set of carcinogens despite variations in carcinoma histopathology. The ability to use microarray analysis to discern an etiology-specific profile among a pathologically heterogeneous group of breast carcinomas may ultimately be valuable in determining the role of environmental chemical carcinogens in human breast cancer risk. JF - Carcinogenesis 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, NIH, Bethesda, MD 20892-4262, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 503 EP - 509 VL - 26 IS - 2 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - DNA, Complementary KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Cluster Analysis KW - Gene Expression Profiling -- methods KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Carcinogens -- toxicity KW - Mammary Neoplasms, Experimental -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Gene Expression Regulation, Neoplastic -- genetics KW - Carcinoma -- genetics KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67369352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+expression+profiling+of+chemically+induced+rat+mammary+gland+cancer.&rft.au=Shan%2C+Liang%3BYu%2C+Minshu%3BSnyderwine%2C+Elizabeth+G&rft.aulast=Shan&rft.aufirst=Liang&rft.date=2005-02-01&rft.volume=26&rft.issue=2&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-10 N1 - Date created - 2005-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Efficacy of Targretin on methylnitrosourea-induced mammary cancers: prevention and therapy dose-response curves and effects on proliferation and apoptosis. AN - 67368269; 15591091 AB - Various aspects of the chemopreventive and chemotherapeutic properties of the RXR receptor agonist Targretin (LGD 1069) were examined in the methylnitrosourea (MNU)-induced model of mammary cancer. The administration of Targretin at dose levels of 60, 20 or 6.7 mg/kg body wt/day by gavage decreased the number of mammary tumors by 96, 85 and 78%, respectively. When Targretin was administered in the diet at 92 and 275 mg/kg diet cancer multiplicities were reduced by 78 and 92%, respectively. A wider range of dietary doses of Targretin at 15, 50 and 150 mg/kg diet reduced the number of mammary tumors by 38, 55 and 70%, respectively. Treatment of rats with different regimens of Targretin (250 mg/kg diet) yielded cancer multiplicities of 4.3 for non-treated rats, 0.5 for rats treated continuously with Targretin, 2.1 for rats treated with Targretin for 8 weeks followed by 10 weeks of the control diet and 1.6 for rats treated with Targretin alternating 3 days on and 4 days off. Targretin was also examined as a therapeutic agent by treating rats with at least one palpable mammary tumor for 5 weeks. A high dose of Targretin (272 mg/kg diet) caused partial or complete regression of approximately 65% of the cancers over this time period. In contrast, in animals treated with 15 mg Targretin/kg diet only 1 of 12 cancers showed significant regression. Finally, the effect of a limited exposure to Targretin (7 days) on cell proliferation and apoptosis in small mammary tumors was determined. Targretin at 150 mg/kg diet strongly decreased proliferation (75%) and increased apoptosis (300%), while a lower dose of Targretin (15 mg/kg diet, which still prevented 30% of cancers) had no effect on apoptosis but did decrease cell proliferation. Determination of serum IGF1 levels showed that treatment of rats with highly effective doses of Targretin at 272 mg/kg diet or at 60 or 20 mg/kg body wt/day by gavage caused significantly decreased serum IGF1 levels. JF - Carcinogenesis AU - Lubet, Ronald A AU - Christov, Konstantin AU - Nunez, Nomeli P AU - Hursting, Steven D AU - Steele, Vernon E AU - Juliana, M Margaret AU - Eto, Isao AU - Grubbs, Clinton J AD - Division of Cancer Prevention, National Cancer Institute, Executive Plaza North, Suite 2110, 6130 Executive Boulevard, Bethesda, MD 20852, USA. lubetr@mail.nih.gov Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 441 EP - 448 VL - 26 IS - 2 SN - 0143-3334, 0143-3334 KW - Antineoplastic Agents KW - 0 KW - Carcinogens KW - Retinoid X Receptors KW - Tamoxifen KW - 094ZI81Y45 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Methylnitrosourea KW - 684-93-5 KW - Index Medicus KW - Rats KW - Animals KW - Methylnitrosourea -- toxicity KW - Carcinogens -- toxicity KW - Insulin-Like Growth Factor I -- metabolism KW - Diet KW - Antineoplastic Agents -- therapeutic use KW - Mammary Neoplasms, Experimental -- chemically induced KW - Tamoxifen -- therapeutic use KW - Apoptosis -- physiology KW - Apoptosis -- drug effects KW - Cell Division -- physiology KW - Cell Division -- drug effects KW - Mammary Neoplasms, Experimental -- drug therapy KW - Retinoid X Receptors -- metabolism KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67368269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Efficacy+of+Targretin+on+methylnitrosourea-induced+mammary+cancers%3A+prevention+and+therapy+dose-response+curves+and+effects+on+proliferation+and+apoptosis.&rft.au=Lubet%2C+Ronald+A%3BChristov%2C+Konstantin%3BNunez%2C+Nomeli+P%3BHursting%2C+Steven+D%3BSteele%2C+Vernon+E%3BJuliana%2C+M+Margaret%3BEto%2C+Isao%3BGrubbs%2C+Clinton+J&rft.aulast=Lubet&rft.aufirst=Ronald&rft.date=2005-02-01&rft.volume=26&rft.issue=2&rft.spage=441&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-10 N1 - Date created - 2005-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C alpha-mediated chemotaxis of neutrophils requires NF-kappa B activity but is independent of TNF alpha signaling in mouse skin in vivo. AN - 67367850; 15661932 AB - Protein kinase C (PKC) isoforms are major regulators of cutaneous homeostasis and mediate inflammation in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). We have previously reported that transgenic mice overexpressing PKCalpha in the skin exhibit severe intraepidermal neutrophilic inflammation and keratinocyte apoptosis when treated topically with TPA. Activation of PKCalpha increases the production of TNFalpha and the transcription of chemotactic factors (MIP-2, KC, S100A8/A9), vascular endothelial growth factor, and GM-CSF in K5-PKCalpha keratinocytes. In response to PKCalpha activation, NF-kappaB translocates to the nucleus and this is associated with IkappaB phosphorylation and degradation. Preventing IkappaB degradation reduces both the expression of inflammation-associated genes and chemoattractant release. To determine whether TNFalpha mediated NF-kappaB translocation and subsequent expression of proinflammatory factors, K5-PKCalpha mice were treated systemically with a dimeric soluble form of p75 TNFR (etanercept) or crossed with mice deficient for both TNFR isoforms, and keratinocytes were cultured in the presence of TNFalpha-neutralizing Abs. The in vivo treatment and TNFR deficiency did not prevent inflammation, and the in vitro treatment did not prevent NF-kappaB nuclear translocation after TPA. Together these results implicate PKCalpha as a regulator of a subset of cutaneous cytokines and chemokines responsible for intraepidermal inflammation independent of TNFalpha. PKCalpha inhibition may have therapeutic benefit in some human inflammatory skin disorders. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Cataisson, Christophe AU - Pearson, Andrea J AU - Torgerson, Sara AU - Nedospasov, Sergei A AU - Yuspa, Stuart H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2005/02/01/ PY - 2005 DA - 2005 Feb 01 SP - 1686 EP - 1692 VL - 174 IS - 3 SN - 0022-1767, 0022-1767 KW - Chemotactic Factors KW - 0 KW - Isoenzymes KW - NF-kappa B KW - Tumor Necrosis Factor-alpha 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 - Keratinocytes -- secretion KW - Cell Nucleus -- metabolism KW - Inflammation -- genetics KW - Mice KW - Mice, Transgenic KW - Isoenzymes -- genetics KW - Chemotactic Factors -- secretion KW - Mice, Knockout KW - Neutrophil Infiltration -- immunology KW - Keratinocytes -- physiology KW - Epidermis -- immunology KW - Inflammation -- prevention & control KW - Neutrophil Infiltration -- genetics KW - Isoenzymes -- physiology KW - Keratinocytes -- enzymology KW - Cells, Cultured KW - Active Transport, Cell Nucleus -- genetics KW - Epidermis -- pathology KW - Inflammation -- immunology KW - Cell Nucleus -- genetics KW - Skin -- enzymology KW - Neutrophils -- immunology KW - Skin -- pathology KW - Protein Kinase C -- genetics KW - Tumor Necrosis Factor-alpha -- physiology KW - NF-kappa B -- physiology KW - Tumor Necrosis Factor-alpha -- secretion KW - Neutrophils -- metabolism KW - Skin -- immunology KW - Chemotaxis, Leukocyte -- immunology KW - Signal Transduction -- genetics KW - Neutrophils -- enzymology KW - Signal Transduction -- immunology KW - Protein Kinase C -- physiology KW - Chemotaxis, Leukocyte -- genetics KW - NF-kappa B -- antagonists & inhibitors KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67367850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Protein+kinase+C+alpha-mediated+chemotaxis+of+neutrophils+requires+NF-kappa+B+activity+but+is+independent+of+TNF+alpha+signaling+in+mouse+skin+in+vivo.&rft.au=Cataisson%2C+Christophe%3BPearson%2C+Andrea+J%3BTorgerson%2C+Sara%3BNedospasov%2C+Sergei+A%3BYuspa%2C+Stuart+H&rft.aulast=Cataisson&rft.aufirst=Christophe&rft.date=2005-02-01&rft.volume=174&rft.issue=3&rft.spage=1686&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 - 2005-03-15 N1 - Date created - 2005-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An application of a weighting method to adjust for nonresponse in standardized incidence ratio analysis of cohort studies. AN - 67364894; 15652718 AB - Cohort studies often conduct periodic follow-up interviews (or waves) to determine disease incidence since the previous follow-up and to update measures of exposure and confounders. The common practice of excluding nonrespondents from standardized incidence ratio (SIR) analyses of these cohorts can bias the estimates of interest if nonrespondents and respondents differ on important characteristics related to outcomes of interest. We propose an analytic approach to reduce the impact of nonresponse in the analyses of SIRs. Logistic regression models controlling baseline information are used to estimate the propensity, or the probability of response; the reciprocals of these propensities are used as weights in the analysis of risk. This is illustrated in the analysis of 15 years of follow-up of a cohort of US radiologic technologists after an initial interview to assess the risk at several cancer sites from occupational radiation exposure. We use information from the baseline survey and certification records to compute the propensity of responding to the second survey. SIRs are computed using Surveillance, Epidemiology, and End Results (SEER) cancer incidence rates. Variances of the SIRs are estimated by a jackknife method that accounts for additional variability resulting from estimation of the weights. We find that, in this application, weighting alters point estimates and confidence limits only to a small degree, thus providing reassurance that the results are robust to nonresponse. This indicates that results from the analyses excluding the missing data may be slightly biased and weighting helps in reducing the nonresponse bias. This method is flexible, practical, easy to use with existing software, and is applicable to missing data from cohorts with baseline information on all subjects. JF - Annals of epidemiology AU - Rao, R Sowmya AU - Sigurdson, Alice J AU - Doody, Michele Morin AU - Graubard, Barry I AD - Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, DHHS, Bethesda, MD 20892-7244, USA. raos@mail.nih.gov Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 129 EP - 136 VL - 15 IS - 2 SN - 1047-2797, 1047-2797 KW - Index Medicus KW - Occupational Exposure KW - Neoplasms, Radiation-Induced -- epidemiology KW - Humans KW - Incidence KW - Data Interpretation, Statistical KW - Follow-Up Studies KW - Time Factors KW - Technology, Radiologic KW - Male KW - Female KW - Logistic Models KW - Cohort Studies KW - Bias (Epidemiology) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67364894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+application+of+a+weighting+method+to+adjust+for+nonresponse+in+standardized+incidence+ratio+analysis+of+cohort+studies.&rft.au=Rao%2C+R+Sowmya%3BSigurdson%2C+Alice+J%3BDoody%2C+Michele+Morin%3BGraubard%2C+Barry+I&rft.aulast=Rao&rft.aufirst=R&rft.date=2005-02-01&rft.volume=15&rft.issue=2&rft.spage=129&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 - 2005-05-05 N1 - Date created - 2005-01-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Epidemiol. 2006 Jun;16(6):501 [16039876] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bovine serum albumin-estrogen compounds differentially alter gonadotropin-releasing hormone-1 neuronal activity. AN - 67363453; 15539555 AB - Steroid hormones regulate a host of physiological processes and behaviors. These actions can occur by genomic mechanisms involving gene transcription or by nongenomic mechanisms proposed to involve receptors associated with the plasma membrane. BSA-conjugated steroid hormones have been extensively used to elucidate signal transduction pathways for these hormones. We have previously shown, using calcium imaging, that 17beta-estradiol (E2) significantly increases GnRH-1 neuronal activity. During the course of these experiments, it became apparent that three different BSA-estrogen compounds have been used in a variety of cell types: 17beta-estradiol 6-O-carboxymethyloxime-BSA (E2-6-BSA); 1,3,5(10)-estratrien-3,16alpha,17beta-triol-6-one 6-O-carboxymethyloxime-BSA (E-6-BSA); and 1,3,5(10)-estratrien-3,17beta-diol 17-hemisuccinate-BSA (E2-17-BSA). The effects of these compounds on GnRH-1 neuronal activity were compared using calcium imaging. E-6-BSA and E2-17-BSA, but not E2-6-BSA, significantly increased all parameters of GnRH-1 neuronal activity. In addition, the effects of these two BSA compounds were reversed by the estrogen receptor antagonist ICI 182,780 but not by inhibition of gene transcription. The effects of E2-17-BSA, but not E-6-BSA were reversed by treatment with pertussis toxin, which blocks G protein-coupled receptors. These data indicate that these compounds cannot be used interchangeably and clearly have different binding properties and/or different effects on target tissues. JF - Endocrinology AU - Temple, Jennifer L AU - Wray, Susan AD - Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 558 EP - 563 VL - 146 IS - 2 SN - 0013-7227, 0013-7227 KW - Anesthetics, Local KW - 0 KW - Serum Albumin, Bovine KW - estradiol-bovine serum albumin KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Tetrodotoxin KW - 4368-28-9 KW - Estradiol KW - 4TI98Z838E KW - Calcium KW - SY7Q814VUP KW - Abridged Index Medicus KW - Index Medicus KW - Calcium -- metabolism KW - Animals KW - Anesthetics, Local -- pharmacology KW - Transfection KW - Mice KW - Cell Line, Tumor KW - Tetrodotoxin -- pharmacology KW - Drug Synergism KW - Female KW - Pregnancy KW - Gonadotropin-Releasing Hormone -- metabolism KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Estradiol -- chemistry KW - Estradiol -- pharmacology KW - Serum Albumin, Bovine -- pharmacology KW - Serum Albumin, Bovine -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67363453?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=Bovine+serum+albumin-estrogen+compounds+differentially+alter+gonadotropin-releasing+hormone-1+neuronal+activity.&rft.au=Temple%2C+Jennifer+L%3BWray%2C+Susan&rft.aulast=Temple&rft.aufirst=Jennifer&rft.date=2005-02-01&rft.volume=146&rft.issue=2&rft.spage=558&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-17 N1 - Date created - 2005-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Negative regulation of TRPC3 channels by protein kinase C-mediated phosphorylation of serine 712. AN - 67363290; 15533987 AB - TRPC3 is a nonselective cation channel member of the "canonical" transient receptor potential (TRPC) family whose members are activated by phospholipase C-coupled receptors. TRPC3 can be activated by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) in a protein kinase C-independent manner. On the other hand, phorbol 12-myristate 13-acetate (PMA) inhibits OAG-mediated TRPC3 channel activation, suggesting that phosphorylation of TRPC3 by protein kinase C is a mechanism of receptor-mediated negative feedback. Here, we show PMA-induced phosphorylation of TRPC3 channels in vivo. We demonstrate by site-directed mutagenesis that a single site containing Ser(712) and conserved among all members of the TRPC family is essential for protein kinase C-mediated negative regulation of TRPC3. In human embryonic kidney 293 cells expressing a TRPC3 mutant in which Ser(712) was replaced by alanine (S712A), PMA failed to block channel activation, whereas wild-type TRPC3 activity was completely inhibited. Phosphorylation of the S712A TRPC3 mutant was not stimulated in response to PMA treatment. Furthermore, S712A TRPC3 mutant-mediated Ca(2+) entry after methacholine activation was significantly greater than that of wild-type TRPC3. These findings demonstrate a dual role for phospholipase C-generated diacylglycerol, which serves as a signal for TRPC3 activation as well as a signal for negative feedback via protein kinase C-mediated phosphorylation. JF - Molecular pharmacology AU - Trebak, Mohamed AU - Hempel, Nadine AU - Wedel, Barbara J AU - Smyth, Jeremy T AU - Bird, Gary St J AU - Putney, James W AD - Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. trebak@niehs.nih.gov Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 558 EP - 563 VL - 67 IS - 2 SN - 0026-895X, 0026-895X KW - Ion Channels KW - 0 KW - TRPC Cation Channels KW - TRPC3 cation channel KW - Serine KW - 452VLY9402 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Point Mutation KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Amino Acid Sequence KW - Cell Line KW - Phosphorylation -- drug effects KW - Protein Kinase C -- physiology KW - Ion Channels -- genetics KW - Serine -- metabolism KW - Serine -- genetics KW - Ion Channels -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67363290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Negative+regulation+of+TRPC3+channels+by+protein+kinase+C-mediated+phosphorylation+of+serine+712.&rft.au=Trebak%2C+Mohamed%3BHempel%2C+Nadine%3BWedel%2C+Barbara+J%3BSmyth%2C+Jeremy+T%3BBird%2C+Gary+St+J%3BPutney%2C+James+W&rft.aulast=Trebak&rft.aufirst=Mohamed&rft.date=2005-02-01&rft.volume=67&rft.issue=2&rft.spage=558&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 - 2005-03-07 N1 - Date created - 2005-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cellular topoisomerase I inhibition and antiproliferative activity by MJ-III-65 (NSC 706744), an indenoisoquinoline topoisomerase I poison. AN - 67363258; 15531731 AB - To overcome camptothecin's (CPT) lactone instability, reversibility of the drug-target interaction, and drug resistance, attempts to synthesize compounds that are CPT-like in their specificity and potency yet display a unique profile have been underway. In this pursuit, we have identified one of the idenoisoquinoline derivatives, MJ-III-65 (NSC 706744; 6-[3-(2-hydroxyethyl)amino-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline) with both similarities and differences from CPT. MJ-III-65 traps topoisomerase I (Top1) reversibly like CPT but with different DNA sequence preferences. Consistent with Top1 poisoning, protein-linked DNA breaks were detected in cells treated with MJ-III-65 at nanomolar concentrations. These MJ-III-65-induced protein-linked DNA breaks were resistant to reversal after an hour of drug removal, compared with CPT, which completely reversed. Studies in human cells in culture found MJ-III-65 to be cytotoxic. Furthermore, limited cross-resistance was observed in camptothecin-resistant cell lines. MJ-III-65 also exhibits antitumor activity in mouse tumor xenografts. JF - Molecular pharmacology AU - Antony, Smitha AU - Kohlhagen, Glenda AU - Agama, Keli AU - Jayaraman, Muthusamy AU - Cao, Shousong AU - Durrani, Farukh A AU - Rustum, Youcef M AU - Cushman, Mark AU - Pommier, Yves AD - Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, 37 Convent Dr., National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 523 EP - 530 VL - 67 IS - 2 SN - 0026-895X, 0026-895X 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 - Growth Inhibitors KW - Indenes KW - Isoquinolines KW - Topoisomerase I Inhibitors KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Animals KW - Xenograft Model Antitumor Assays -- methods KW - Dose-Response Relationship, Drug KW - Humans KW - Enzyme Inhibitors -- pharmacology KW - Mice, Nude KW - Mice KW - Cell Line, Tumor KW - Insects KW - Female KW - DNA Topoisomerases, Type I -- metabolism KW - Cell Line KW - Cell Proliferation -- drug effects KW - Isoquinolines -- pharmacology KW - Indenes -- pharmacology KW - Growth Inhibitors -- pharmacology KW - Indenes -- poisoning KW - Growth Inhibitors -- poisoning KW - Isoquinolines -- poisoning UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67363258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Cellular+topoisomerase+I+inhibition+and+antiproliferative+activity+by+MJ-III-65+%28NSC+706744%29%2C+an+indenoisoquinoline+topoisomerase+I+poison.&rft.au=Antony%2C+Smitha%3BKohlhagen%2C+Glenda%3BAgama%2C+Keli%3BJayaraman%2C+Muthusamy%3BCao%2C+Shousong%3BDurrani%2C+Farukh+A%3BRustum%2C+Youcef+M%3BCushman%2C+Mark%3BPommier%2C+Yves&rft.aulast=Antony&rft.aufirst=Smitha&rft.date=2005-02-01&rft.volume=67&rft.issue=2&rft.spage=523&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 - 2005-03-07 N1 - Date created - 2005-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroadaptations of total levels of adenylate cyclase, protein kinase A, tyrosine hydroxylase, cdk5 and neurofilaments in the nucleus accumbens and ventral tegmental area do not correlate with expression of sensitized or tolerant locomotor responses to cocaine. AN - 67361887; 15659224 AB - Neuroadaptations induced by high-dose cocaine treatment have been hypothesized to persist after the cessation of drug treatment and mediate the expression of sensitization and tolerance to cocaine. We looked for evidence of these neuroadaptations in rats receiving more modest behaviorally effective cocaine treatments. Rats were exposed to either a sensitizing regimen of seven once-daily injections of 15 mg/kg cocaine or a tolerance-producing regimen involving a continuous infusion of the same daily dose. We assessed enzyme activity levels of protein kinase A and adenylate cyclase, and protein levels of tyrosine hydroxylase, cdk5 and neurofilaments in the nucleus accumbens and ventral tegmental area. Only protein kinase A activity levels were altered by cocaine treatment, but this alteration persisted for only 7 days, whereas a sensitized locomotor response was still evident at 21 days. Although behavioral tolerance to cocaine was seen the day after the termination of treatment, none of the molecular measures was altered on this or any other day. Thus, although increased protein kinase A activity can temporarily modulate sensitized responses to cocaine, alterations in total levels of the molecules assessed in our study do not correlate with the expression of sensitized or tolerant locomotor responses to cocaine. JF - Journal of neurochemistry AU - Hope, B T AU - Crombag, H S AU - Jedynak, J P AU - Wise, R A AD - National Institute on Drug Abuse, National Institutes of Health/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. bhope@intra.nida.nih.gov Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 536 EP - 545 VL - 92 IS - 3 SN - 0022-3042, 0022-3042 KW - Neurofilament Proteins KW - 0 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 - Rats KW - Cyclin-Dependent Kinases -- metabolism KW - Animals KW - Adaptation, Physiological -- drug effects KW - Tyrosine 3-Monooxygenase -- metabolism KW - Rats, Sprague-Dawley KW - Drug Tolerance -- physiology KW - Neurofilament Proteins -- metabolism KW - Time Factors KW - Male KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Cocaine-Related Disorders -- enzymology KW - Adenylyl Cyclases -- metabolism KW - Nucleus Accumbens -- metabolism KW - Ventral Tegmental Area -- metabolism KW - Motor Activity -- drug effects KW - Cocaine -- pharmacology KW - Cocaine-Related Disorders -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67361887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Neuroadaptations+of+total+levels+of+adenylate+cyclase%2C+protein+kinase+A%2C+tyrosine+hydroxylase%2C+cdk5+and+neurofilaments+in+the+nucleus+accumbens+and+ventral+tegmental+area+do+not+correlate+with+expression+of+sensitized+or+tolerant+locomotor+responses+to+cocaine.&rft.au=Hope%2C+B+T%3BCrombag%2C+H+S%3BJedynak%2C+J+P%3BWise%2C+R+A&rft.aulast=Hope&rft.aufirst=B&rft.date=2005-02-01&rft.volume=92&rft.issue=3&rft.spage=536&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 - 2005-06-24 N1 - Date created - 2005-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human cocaine-seeking behavior and its control by drug-associated stimuli in the laboratory. AN - 67361102; 15536497 AB - Second-order schedules of drug self-administration were developed to incorporate the effects of drug-related environmental stimuli into an animal model of drug abuse, making it more similar to human situations. Ironically, little is known about how human subjects behave under these schedules. In this study, human volunteers with a history of cocaine use worked on a second-order schedule in which every 100th lever response produced an auditory-visual brief stimulus (2 s). The first stimulus produced after 1 h was extended to 10 s and paired with an intravenous injection of cocaine (25 mg). Up to three injections were allowed per session. In different phases of the experiment, presentation of the brief stimulus was discontinued and/or saline solution (placebo) was injected instead of cocaine. Injections of cocaine were found to maintain responding even when the brief stimulus was not presented. Placebo injections alone did not maintain responding. In contrast, the brief stimulus maintained high levels of responding under placebo conditions, even though self-reports indicated that subjects could clearly discriminate that they were not receiving cocaine. These results demonstrate that drug-related environmental stimuli can maintain persistent drug seeking during periods of drug unavailability. As this procedure directly measures the effects of stimuli on drug seeking, it may provide a valuable complement to indirect measures, such as self-reports of craving, that are often used with human subjects. The similarity of the response patterns in humans and animals also supports the use of second-order schedules in animals as a valid model of human drug seeking. JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology AU - Panlilio, Leigh V AU - Yasar, Sevil AU - Nemeth-Coslett, Ro AU - Katz, Jonathan L AU - Henningfield, Jack E AU - Solinas, Marcello AU - Heishman, Stephen J AU - Schindler, Charles W AU - Goldberg, Steven R AD - Preclinical Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 433 EP - 443 VL - 30 IS - 2 SN - 0893-133X, 0893-133X KW - Index Medicus KW - Hemodynamics -- drug effects KW - Heart Rate -- drug effects KW - Self Administration KW - Reinforcement Schedule KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Male KW - Cocaine-Related Disorders -- psychology KW - Cues UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67361102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Human+cocaine-seeking+behavior+and+its+control+by+drug-associated+stimuli+in+the+laboratory.&rft.au=Panlilio%2C+Leigh+V%3BYasar%2C+Sevil%3BNemeth-Coslett%2C+Ro%3BKatz%2C+Jonathan+L%3BHenningfield%2C+Jack+E%3BSolinas%2C+Marcello%3BHeishman%2C+Stephen+J%3BSchindler%2C+Charles+W%3BGoldberg%2C+Steven+R&rft.aulast=Panlilio&rft.aufirst=Leigh&rft.date=2005-02-01&rft.volume=30&rft.issue=2&rft.spage=433&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 - 2005-02-15 N1 - Date created - 2005-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - POT1 and TRF2 cooperate to maintain telomeric integrity. AN - 67359513; 15657433 AB - Mammalian telomeric DNA contains duplex TTAGGG repeats and single-stranded overhangs. POT1 (protection of telomeres 1) is a telomere-specific single-stranded DNA-binding protein, highly conserved in eukaryotes. The biological function of human POT1 is not well understood. In the present study, we demonstrate that POT1 plays a key role in telomeric end protection. The reduction of POT1 by RNA interference led to the loss of telomeric single-stranded overhangs and induced apoptosis, chromosomal instability, and senescence in cells. POT1 and TRF2 interacted with each other to form a complex with telomeric DNA. A dominant negative TRF2, TRF2(DeltaBDeltaM), bound to POT1 and prevented it from binding to telomeres. POT1 overexpression protected against TRF2(DeltaBDeltaM)-induced loss of telomeric single-stranded overhangs, chromosomal instability, and senescence. These results demonstrate that POT1 and TRF2 share in part in the same pathway for telomere capping and suggest that POT1 binds to the telomeric single-stranded DNA in the D-loop and cooperates with TRF2 in t-loop maintenance. JF - Molecular and cellular biology AU - Yang, Qin AU - Zheng, Yun-Ling AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute/NIH, Bldg. 37, Rm. 3068, 37 Convent Drive, Bethesda, MD 20892-4255, USA. Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 1070 EP - 1080 VL - 25 IS - 3 SN - 0270-7306, 0270-7306 KW - POT1 protein, human KW - 0 KW - RNA, Small Interfering KW - Telomere-Binding Proteins KW - Telomeric Repeat Binding Protein 2 KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - Chromosomal Instability -- physiology KW - In Situ Hybridization, Fluorescence KW - RNA, Small Interfering -- metabolism KW - Protein Binding KW - Fibroblasts -- metabolism KW - Telomeric Repeat Binding Protein 2 -- metabolism KW - Telomere -- metabolism KW - Apoptosis -- physiology KW - Cell Aging -- physiology KW - Telomere-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67359513?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=POT1+and+TRF2+cooperate+to+maintain+telomeric+integrity.&rft.au=Yang%2C+Qin%3BZheng%2C+Yun-Ling%3BHarris%2C+Curtis+C&rft.aulast=Yang&rft.aufirst=Qin&rft.date=2005-02-01&rft.volume=25&rft.issue=3&rft.spage=1070&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 - 2005-03-09 N1 - Date created - 2005-01-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 2000 Mar;20(5):1659-68 [10669743] Science. 1995 Dec 8;270(5242):1663-7 [7502076] Nature. 2000 Nov 2;408(6808):53-6 [11081503] Nature. 2000 Nov 9;408(6809):248-54 [11089982] Cell. 2001 Feb 9;104(3):387-96 [11239396] Nucleic Acids Res. 2001 Apr 1;29(7):E35 [11266570] Science. 2001 May 11;292(5519):1171-5 [11349150] Science. 2001 May 11;292(5519):1075-6 [11352055] Cell. 2001 Sep 21;106(6):661-73 [11572773] EMBO J. 2001 Oct 1;20(19):5532-40 [11574485] EMBO J. 2001 Nov 1;20(21):6127-39 [11689452] Oncogene. 2002 Jan 21;21(4):503-11 [11850775] Science. 2002 Mar 29;295(5564):2446-9 [11923537] Nat Biotechnol. 2002 Jul;20(7):682-8 [12089552] EMBO J. 2002 Aug 15;21(16):4338-48 [12169636] Mol Cell Biol. 2002 Nov;22(22):8079-87 [12391173] Cancer Cell. 2002 Oct;2(4):257-65 [12398889] Biochemistry. 2002 Dec 10;41(49):14560-8 [12463756] Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):527-31 [12515865] Nat Genet. 2003 Apr;33(4):492-6 [12652299] Cancer Lett. 2003 May 15;194(2):155-62 [12757973] Cancer Lett. 2003 May 15;194(2):189-97 [12757977] Cold Spring Harb Symp Quant Biol. 2000;65:253-63 [12760039] Curr Biol. 2003 May 27;13(11):942-6 [12781132] Science. 2003 Jun 6;300(5625):1542-8 [12791985] Mol Cells. 2003 Apr 30;15(2):164-75 [12803478] Nature. 2003 Jun 26;423(6943):1013-8 [12768206] Mol Cell Biol. 2004 Apr;24(8):3552-61 [15060173] Dev Genet. 1996;18(2):173-9 [8934879] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13902-7 [8943033] Nature. 1997 Feb 20;385(6618):740-3 [9034193] Cell. 1997 Mar 7;88(5):657-66 [9054505] EMBO J. 1997 Jun 16;16(12):3705-14 [9218811] Genes Dev. 1997 Nov 1;11(21):2801-9 [9353250] Nat Med. 1997 Nov;3(11):1271-4 [9359704] Science. 1998 Jan 16;279(5349):349-52 [9454332] Cell. 1998 Feb 6;92(3):401-13 [9476899] Cell. 1998 Dec 23;95(7):963-74 [9875850] Science. 1999 Feb 26;283(5406):1321-5 [10037601] Cell. 1999 May 14;97(4):503-14 [10338214] Genes Dev. 1999 Jun 1;13(11):1355-60 [10364153] Mutat Res. 1999 Jun 23;434(2):99-107 [10422538] J Biol Chem. 2004 Nov 5;279(45):47264-71 [15316005] Cell. 2003 Jul 25;114(2):241-53 [12887925] Nat Rev Cancer. 2003 Aug;3(8):623-7 [12894250] Curr Biol. 2003 Sep 2;13(17):1549-56 [12956959] Eur J Cell Biol. 2003 Sep;82(9):441-6 [14582532] Nature. 2003 Nov 13;426(6963):198-203 [14614509] Cancer Res. 2004 Jan 15;64(2):523-9 [14744765] Mol Cell Biol. 2004 Mar;24(5):2091-102 [14966288] J Biol Chem. 2004 Mar 26;279(13):13241-8 [14715659] Nat Rev Mol Cell Biol. 2004 Apr;5(4):323-9 [15071557] Mol Cell Biol. 2004 Jun;24(12):5587-94 [15169917] Nat Cell Biol. 2004 Jul;6(7):673-80 [15181449] Genes Dev. 2004 Jul 15;18(14):1649-54 [15231715] Cell. 1984 Sep;38(2):501-10 [6432344] Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7006-10 [1871116] EMBO J. 1992 May;11(5):1921-9 [1582420] Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8861-5 [8090736] J Biol Chem. 2000 Mar 31;275(13):9636-44 [10734115] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exploiting gene-environment independence in family-based case-control studies: increased power for detecting associations, interactions and joint effects. AN - 67358462; 15593088 AB - Family-based case-control studies are popularly used to study the effect of genes and gene-environment interactions in the etiology of rare complex diseases. We consider methods for the analysis of such studies under the assumption that genetic susceptibility (G) and environmental exposures (E) are independently distributed of each other within families in the source population. Conditional logistic regression, the traditional method of analysis of the data, fails to exploit the independence assumption and hence can be inefficient. Alternatively, one can estimate the multiplicative interaction between G and E more efficiently using cases only, but the required population-based G-E independence assumption is very stringent. In this article, we propose a novel conditional likelihood framework for exploiting the within-family G-E independence assumption. This approach leads to a simple and yet highly efficient method of estimating interaction and various other risk parameters of scientific interest. Moreover, we show that the same paradigm also leads to a number of alternative and even more efficient methods for analysis of family-based case-control studies when parental genotype information is available on the case-control study participants. Based on these methods, we evaluate different family-based study designs by examining their relative efficiencies to each other and their efficiencies compared to a population-based case-control design of unrelated subjects. These comparisons reveal important design implications. Extensions of the methodologies for dealing with complex family studies are also discussed. 2004 Wiley-Liss, Inc. JF - Genetic epidemiology AU - Chatterjee, Nilanjan AU - Kalaylioglu, Zeynep AU - Carroll, Raymond J AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland 20852, USA. chattern@mail.nih.gov Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 138 EP - 156 VL - 28 IS - 2 SN - 0741-0395, 0741-0395 KW - Index Medicus KW - Alleles KW - Logistic Models KW - Epidemiologic Methods KW - Risk Factors KW - Humans KW - Research Design KW - Likelihood Functions KW - Genotype KW - Models, Genetic KW - Environmental Exposure KW - Case-Control Studies KW - Genetic Predisposition to Disease UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67358462?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetic+epidemiology&rft.atitle=Exploiting+gene-environment+independence+in+family-based+case-control+studies%3A+increased+power+for+detecting+associations%2C+interactions+and+joint+effects.&rft.au=Chatterjee%2C+Nilanjan%3BKalaylioglu%2C+Zeynep%3BCarroll%2C+Raymond+J&rft.aulast=Chatterjee&rft.aufirst=Nilanjan&rft.date=2005-02-01&rft.volume=28&rft.issue=2&rft.spage=138&rft.isbn=&rft.btitle=&rft.title=Genetic+epidemiology&rft.issn=07410395&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-12 N1 - Date created - 2005-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acute hemorrhagic myocardial necrosis and sudden death of rats exposed to a combination of ephedrine and caffeine. AN - 67345187; 15537744 AB - Because of possible side effects of herbal medicines containing ephedrine and guarana-derived caffeine, including increased risk of stroke, myocardial infarction, and sudden death, the Food and Drug Administration recently banned the sale of ephedra-containing products, specifically over-the-counter dietary supplements. We report cardiac in 7- and 14-week-old male F344 rats exposed by gavage to ephedrine(25 mg/kg) and caffeine (30 mg/kg) administered in combination for one or two days. The ephedrine-caffeine dosage was approximately 12- and 1.4-fold, respectively, above average human exposure, based on a mg/m2 body surface-area comparison. Several (5/7) of the exposed 14-week-old rats died or were sacrificed in extremis 4-5 h after the first dosing. In these hearts, changes were observed chiefly in the interventricular septum but also left and right ventricular walls. Massive interstitial hemorrhage, with degeneration of myofibers, occurred at the subendocardial myocardium of the left ventricle and interventricular septum. Immunostaining for cleaved caspase-3 and hyperphosphorylated H2A.X, a histone variant that becomes hyperphosphorylated during apoptosis, indicated multifocal generalized positive staining of degenerating myofibers and fragmenting nuclei, respectively. The Barbeito-Lopez trichrome stain revealed generalized patchy yellow myofibers consistent with degeneration and/or coagulative necrosis. In ephedrine-caffeine-treated animals terminated after the second dosing, foci of myocardial degeneration and necrosis were already infiltrated by mixed inflammatory cells. The myocardial necrosis may occur secondarily to intense diffuse vasoconstriction of the coronary arterial system with decreased myocardial perfusion. Our work shows the direct relationship between combined ephedrine and caffeine exposure and cardiac pathology. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Nyska, Abraham AU - Murphy, Elizabeth AU - Foley, Julie F AU - Collins, Bradley J AU - Petranka, John AU - Howden, Reuben AU - Hanlon, Paul AU - Dunnick, June K AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. nyska@niehs.nih.gov Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 388 EP - 396 VL - 83 IS - 2 SN - 1096-6080, 1096-6080 KW - Adrenergic Agents KW - 0 KW - Central Nervous System Stimulants KW - Drug Combinations KW - Caffeine KW - 3G6A5W338E KW - CASP3 protein, human KW - EC 3.4.22.- KW - Casp3 protein, rat KW - Caspase 3 KW - Caspases KW - Ephedrine KW - GN83C131XS KW - Index Medicus KW - Acute Disease KW - Administration, Oral KW - Animals KW - Drug Interactions KW - Myocardium -- pathology KW - Heart -- drug effects KW - Caspases -- metabolism KW - Myocardium -- metabolism KW - Rats KW - Rats, Inbred F344 KW - Necrosis KW - Hemorrhage -- pathology KW - Hemorrhage -- chemically induced KW - Staining and Labeling KW - Male KW - Myocardial Infarction -- pathology KW - Adrenergic Agents -- toxicity KW - Myocardial Infarction -- metabolism KW - Myocardial Infarction -- chemically induced KW - Caffeine -- administration & dosage KW - Caffeine -- toxicity KW - Ephedrine -- administration & dosage KW - Death, Sudden -- etiology KW - Central Nervous System Stimulants -- toxicity KW - Central Nervous System Stimulants -- administration & dosage KW - Ephedrine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67345187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Acute+hemorrhagic+myocardial+necrosis+and+sudden+death+of+rats+exposed+to+a+combination+of+ephedrine+and+caffeine.&rft.au=Nyska%2C+Abraham%3BMurphy%2C+Elizabeth%3BFoley%2C+Julie+F%3BCollins%2C+Bradley+J%3BPetranka%2C+John%3BHowden%2C+Reuben%3BHanlon%2C+Paul%3BDunnick%2C+June+K&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=2005-02-01&rft.volume=83&rft.issue=2&rft.spage=388&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 - 2005-05-05 N1 - Date created - 2005-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene expression profiling of NRF2-mediated protection against oxidative injury. AN - 67336186; 15629862 AB - Nuclear factor E2 p45-related factor 2 (NRF2) contributes to cellular protection against oxidative insults and chemical carcinogens via transcriptional activation of antioxidant/detoxifying enzymes. To understand the molecular basis of NRF2-mediated protection against oxidative lung injury, pulmonary gene expression profiles were characterized in Nrf2-disrupted (Nrf2(-/-)) and wild-type (Nrf2(+/+)) mice exposed to hyperoxia or air. Genes expressed constitutively higher in Nrf2(+/+) mice than in Nrf2(-/-) mice included antioxidant defense enzyme and immune cell receptor genes. Higher basal expression of heat shock protein and structural genes was detected in Nrf2(-/-) mice relative to Nrf2(+/+) mice. Hyperoxia enhanced expression of 175 genes (> or = twofold) and decreased expression of 100 genes (> or =50%) in wild-type mice. Hyperoxia-induced upregulation of many well-known/new antioxidant/defense genes (e.g., Txnrd1, Ex, Cp-2) and other novel genes (e.g., Pkc-alpha, Tcf-3, Ppar-gamma) was markedly greater in Nrf2(+/+) mice than in Nrf2(-/-) mice. In contrast, induced expression of genes encoding extracellular matrix and cytoskeletal proteins was higher in Nrf2(-/-) mice than in Nrf2(+/+) mice. These NRF2-dependent gene products might have key roles in protection against hyperoxic lung injury. Results from our global gene expression profiles provide putative downstream molecular mechanisms of oxygen tissue toxicity. JF - Free radical biology & medicine AU - Cho, Hye-Youn AU - Reddy, Sekhar P AU - Debiase, Andrea AU - Yamamoto, Masayuki AU - Kleeberger, Steven R AD - Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA. cho2@niehs.nih.gov Y1 - 2005/02/01/ PY - 2005 DA - 2005 Feb 01 SP - 325 EP - 343 VL - 38 IS - 3 SN - 0891-5849, 0891-5849 KW - Antioxidants KW - 0 KW - DNA-Binding Proteins KW - NF-E2-Related Factor 2 KW - Nfe2l2 protein, mouse KW - Nuclear Proteins KW - RNA, Messenger KW - Trans-Activators KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Mice, Inbred ICR KW - Nuclear Proteins -- genetics KW - Oxygen -- toxicity KW - Mice KW - RNA, Messenger -- genetics KW - Models, Biological KW - Mice, Knockout KW - Gene Expression Profiling KW - Antioxidants -- metabolism KW - RNA, Messenger -- metabolism KW - Atmosphere Exposure Chambers KW - Nuclear Proteins -- metabolism KW - Time Factors KW - Immunohistochemistry KW - Trans-Activators -- metabolism KW - Hyperoxia -- pathology KW - Trans-Activators -- genetics KW - Hyperoxia -- metabolism KW - Lung -- drug effects KW - DNA-Binding Proteins -- genetics KW - Lung -- pathology KW - Lung -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67336186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+expression+profiling+of+NRF2-mediated+protection+against+oxidative+injury.&rft.au=Cho%2C+Hye-Youn%3BReddy%2C+Sekhar+P%3BDebiase%2C+Andrea%3BYamamoto%2C+Masayuki%3BKleeberger%2C+Steven+R&rft.aulast=Cho&rft.aufirst=Hye-Youn&rft.date=2005-02-01&rft.volume=38&rft.issue=3&rft.spage=325&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 - 2005-06-16 N1 - Date created - 2005-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Truncated N-terminal mutants of SV40 large T antigen as minimal immortalizing agents for CNS cells. AN - 67336115; 15629761 AB - Immortalized central nervous system (CNS) cell lines are useful as in vitro models for innumerable purposes such as elucidating biochemical pathways, studies of effects of drugs, and ultimately, such cells may also be useful for neural transplantation. The SV40 large T (LT) oncoprotein, commonly used for immortalization, interacts with several cell cycle regulatory factors, including binding and inactivating p53 and retinoblastoma family cell-cycle regulators. In an attempt to define the minimal requirements of SV40 T antigen for immortalizing cells of CNS origin, we constructed T155c, encoding the N-terminal 155 amino acids of LT. The p53 binding region is known to reside in the C-terminal region of LT. An additional series of mutants was produced to further narrow the molecular targets for immortalization, and plasmid vectors were constructed for each. In a p53 temperature sensitive cell line model, T64-7B, expression of T155c and all constructs having mutations outside of the first 82 amino acids were capable of overriding cell-cycle block at the non-permissive growth temperature. Several cell lines were produced from fetal rat mesencephalic and cerebral cortical cultures using the T155c construct. The E107K construct contained a mutation in the Rb binding region, but was nonetheless capable of overcoming cell cycle block in T64-7B cell and immortalizing primary cultured cells. Cells immortalized with T155c were often highly dependent on the presence of bFGF for growth. Telomerase activity, telomere length, growth rates, and integrity of the p53 gene in cells immortalized with T155c did not change over 100 population doublings in culture, indicating that cells immortalized with T155c were generally stable during long periods of continuous culture. JF - Experimental neurology AU - Freed, William J AU - Zhang, Peisu AU - Sanchez, Joseph F AU - Dillon-Carter, Ora AU - Coggiano, Mark AU - Errico, Stacie L AU - Lewis, Brian D AU - Truckenmiller, Mary Ellen AD - Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. wfreed@intra.nida.nih.gov Y1 - 2005/02// PY - 2005 DA - February 2005 SP - S45 EP - S59 VL - 191 Suppl 1 SN - 0014-4886, 0014-4886 KW - Antigens, Viral, Tumor KW - 0 KW - Peptide Fragments KW - Tumor Suppressor Protein p53 KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Telomerase KW - EC 2.7.7.49 KW - Index Medicus KW - Clone Cells KW - Fibroblast Growth Factor 2 -- pharmacology KW - Animals KW - Fibroblasts -- drug effects KW - Temperature KW - Cell Division -- drug effects KW - Fibroblasts -- cytology KW - Fibroblasts -- metabolism KW - Mutagenesis, Site-Directed KW - Rats KW - Rats, Sprague-Dawley KW - Telomere -- metabolism KW - Telomere -- chemistry KW - Transfection KW - Cells, Cultured KW - Cell Line, Transformed KW - Tumor Suppressor Protein p53 -- genetics KW - Cell Cycle -- genetics KW - Telomerase -- metabolism KW - Mesencephalon -- metabolism KW - Peptide Fragments -- biosynthesis KW - Cerebral Cortex -- cytology KW - Peptide Fragments -- genetics KW - Cerebral Cortex -- metabolism KW - Cerebral Cortex -- embryology KW - Antigens, Viral, Tumor -- genetics KW - Simian virus 40 -- genetics KW - Cell Transformation, Viral -- genetics KW - Mesencephalon -- embryology KW - Mesencephalon -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67336115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Truncated+N-terminal+mutants+of+SV40+large+T+antigen+as+minimal+immortalizing+agents+for+CNS+cells.&rft.au=Freed%2C+William+J%3BZhang%2C+Peisu%3BSanchez%2C+Joseph+F%3BDillon-Carter%2C+Ora%3BCoggiano%2C+Mark%3BErrico%2C+Stacie+L%3BLewis%2C+Brian+D%3BTruckenmiller%2C+Mary+Ellen&rft.aulast=Freed&rft.aufirst=William&rft.date=2005-02-01&rft.volume=191+Suppl+1&rft.issue=&rft.spage=S45&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 - 2005-03-29 N1 - Date created - 2005-01-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell Transplant. 2000 Mar-Apr;9(2):153-68 [10811390] Cell. 2000 Aug 18;102(4):407-10 [10966103] Prog Brain Res. 2000;127:49-65 [11142044] EMBO J. 2001 Jan 15;20(1-2):295-304 [11226179] Oncogene. 1994 Mar;9(3):719-25 [8108114] J Virol. 1994 Oct;68(10):6180-7 [8083958] Crit Rev Oncog. 1994;5(4):331-57 [7711112] EMBO J. 1995 Sep 1;14(17):4240-8 [7556065] Oncogene. 1995 Dec 7;11(11):2295-302 [8570180] J Virol. 1996 May;70(5):2781-8 [8627752] J Comp Neurol. 1995 Nov 27;362(4):524-34 [8636465] Mol Cell Biol. 1996 Jul;16(7):3454-64 [8668161] Cell Transplant. 1996 Sep-Oct;5(5):563-75 [8889215] Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12861-6 [8917510] Mol Cell Biol. 1997 Aug;17(8):4761-73 [9234732] Eur J Cancer. 1997 Apr;33(5):703-9 [9282108] Eur J Cancer. 1997 Apr;33(5):716-26 [9282110] Eur J Cancer. 1997 Apr;33(5):735-49 [9282112] Eur J Cancer. 1997 Apr;33(5):792-800 [9282119] Cell. 1997 Nov 28;91(5):649-59 [9393858] Cell Tissue Res. 1998 Feb;291(2):175-89 [9426306] Mol Cell Biol. 1998 Mar;18(3):1408-15 [9488456] Cell. 1998 Mar 20;92(6):713-23 [9529248] J Virol. 1998 Jul;72(7):5329-34 [9620985] Trends Biochem Sci. 1998 Jun;23(6):222-7 [9644977] Genes Dev. 1998 Aug 1;12(15):2424-33 [9694806] J Virol. 1999 Apr;73(4):3102-7 [10074161] Mol Carcinog. 1999 Mar;24(3):209-17 [10204805] Exp Cell Res. 1999 Aug 25;251(1):121-7 [10438577] Biologicals. 1999 Mar;27(1):23-8 [10441399] Virology. 1988 Jan;162(1):76-89 [2827389] Cell. 1988 Jul 15;54(2):275-83 [2839300] J Cell Biol. 1988 Nov;107(5):1977-86 [3053737] Cancer Res. 1994 Jul 15;54(14):3864-7 [8033108] Exp Neurol. 1994 Jun;127(2):207-18 [7518394] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6914-8 [8041720] Mol Cell Biol. 1994 Sep;14(9):6244-52 [8065356] Exp Neurol. 1994 Aug;128(2):191-201 [8076662] Oncogene. 2001 May 10;20(21):2671-82 [11420679] Exp Neurol. 2002 Jun;175(2):318-37 [12061863] Exp Neurol. 2002 Jun;175(2):370-87 [12061867] Cell Transplant. 2002;11(3):251-9 [12075990] Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16226-31 [12446840] Ann Med Exp Biol Fenn. 1966;44(2):242-54 [4290661] J Virol. 1975 Mar;15(3):599-612 [163374] Proc Natl Acad Sci U S A. 1978 May;75(5):2165-9 [209456] Proc Natl Acad Sci U S A. 1978 May;75(5):2473-7 [209467] Nature. 1979 Mar 15;278(5701):261-3 [218111] Cell. 1979 May;17(1):43-52 [222475] Cell. 1982 Feb;28(2):387-94 [6277513] Cell. 1982 Sep;30(2):469-80 [6291770] Cell. 1985 Dec;43(2 Pt 1):405-13 [3907856] Mol Cell Biol. 1986 Apr;6(4):1172-8 [3023875] Cell. 1987 Jan 30;48(2):321-30 [3026642] J Virol. 1990 Jun;64(6):2895-900 [2159550] Cell. 1990 Aug 24;62(4):671-80 [2143698] Virology. 1990 Sep;178(1):15-34 [2167547] Genes Dev. 1991 Feb;5(2):151-9 [1995413] Mol Cell Biol. 1991 Apr;11(4):1988-95 [1706474] Cell. 1991 Aug 23;66(4):713-29 [1878969] J Virol. 1992 Mar;66(3):1289-93 [1310750] J Mol Biol. 1992 Jun 20;225(4):951-60 [1613801] Nucleic Acids Res. 1993 Feb 11;21(3):713-7 [8441680] J Virol. 1993 Apr;67(4):1817-29 [8383212] J Virol. 1994 Mar;68(3):1334-41 [8107198] Annu Rev Neurosci. 1989;12:47-65 [2648957] Cell. 1990 Jan 12;60(1):167-76 [2153055] J Virol. 2000 Jan;74(2):864-74 [10623749] Nat Cell Biol. 2000 Apr;2(4):E65-7 [10783254] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Healthy Living Project: An Individually Tailored, Multidimensional Intervention for HIV-Infected Persons AN - 61564350; 200502285 AB - The NIMH Healthy Living Project (HLP), a randomized behavioral intervention trial for people living with HIV, enrolled 943 individuals, including women, heterosexual men, injection drug users, & men who have sex with men from Los Angeles, Milwaukee, New York, & San Francisco. The intervention, which is based on qualitative formative research & Ewart's Social Action Theory, addresses three interrelated aspects of living with HIV: stress & coping, transmission risk behavior, & medication adherence. Fifteen 90-minute structured sessions, divided into 3 modules of five sessions each, are delivered to individuals. Sessions are tailored to individuals within a structure that uses role -- plays, problem solving, & goal setting techniques. A 'Life Project' -- or overarching goal related to personal striving -- provides continuity throughout sessions. Because this is an ongoing project with efficacy yet to be established, we do not report intervention outcomes. However, the intervention was designed to be useful for prevention case management, settings where repeated one-on-one contact is possible, & where a structured but highly individualized intervention approach is desired. 1 Table, 2 Figures, 68 References. Adapted from the source document. JF - AIDS Education and Prevention AU - Gore-Felton, Cheryl AU - Rotheram-Borus, Mary Jane AU - Weinhardt, Lance S AU - Kelly, Jeffrey A AU - Lightfoot, Marguerita AU - Kirshenbaum, Sheri B AU - Johnson, Mallory O AU - Chesney, Margaret A AU - Catz, Sheryl L AU - Ehrhardt, Anke A AU - Remien, Robert H AU - Morin, Stephen F AU - NIMH Healthy Living Project Team AD - Center AIDS Intervention Research, Medical Coll Wisconsin, Milwaukee ; NIMH Healthy Living Project Team Y1 - 2005/02// PY - 2005 DA - February 2005 SP - 21 EP - 39 VL - 17 IS - SuppA SN - 0899-9546, 0899-9546 KW - Los Angeles, California KW - New York City, New York KW - Treatment Programs KW - Treatment Compliance KW - Acquired Immune Deficiency Syndrome KW - Intervention KW - Case Management KW - Wisconsin KW - Coping KW - San Francisco, California KW - article KW - 6126: acquired immune deficiency syndrome (AIDS) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61564350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+Education+and+Prevention&rft.atitle=The+Healthy+Living+Project%3A+An+Individually+Tailored%2C+Multidimensional+Intervention+for+HIV-Infected+Persons&rft.au=Gore-Felton%2C+Cheryl%3BRotheram-Borus%2C+Mary+Jane%3BWeinhardt%2C+Lance+S%3BKelly%2C+Jeffrey+A%3BLightfoot%2C+Marguerita%3BKirshenbaum%2C+Sheri+B%3BJohnson%2C+Mallory+O%3BChesney%2C+Margaret+A%3BCatz%2C+Sheryl+L%3BEhrhardt%2C+Anke+A%3BRemien%2C+Robert+H%3BMorin%2C+Stephen+F%3BNIMH+Healthy+Living+Project+Team&rft.aulast=Gore-Felton&rft.aufirst=Cheryl&rft.date=2005-02-01&rft.volume=17&rft.issue=SuppA&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=AIDS+Education+and+Prevention&rft.issn=08999546&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Number of references - 68 N1 - Last updated - 2016-09-28 N1 - CODEN - AEPREO N1 - SubjectsTermNotLitGenreText - Treatment Programs; Intervention; Acquired Immune Deficiency Syndrome; Coping; Treatment Compliance; Case Management; San Francisco, California; Los Angeles, California; Wisconsin; New York City, New York ER - TY - JOUR T1 - Use of amiodarone for atrial fibrillation in patients with preexisting pulmonary disease in the AFFIRM Study AN - 230367752; 15670555 AB - In the Atrial Fibrillation Follow-up Investigation of Rhythm Management study, preexisting pulmonary disease did not preclude the use of amiodarone. Preexisting pulmonary disease was associated with a higher risk of pulmonary death and had a higher risk of diagnosed amiodarone pulmonary toxicity. However, use of amiodarone in the presence of preexisting pulmonary disease did not increase pulmonary death and all-cause mortality rates. Cautious use of amiodarone to treat atrial fibrillation appears acceptable in elderly patients with atrial fibrillation, even if preexisting pulmonary disease is present. [PUBLICATION ABSTRACT] JF - The American Journal of Cardiology AU - Olshansky, Brian AU - Sami, Magdi AU - Rubin, Andrew AU - Kostis, John AU - et al Y1 - 2005/02/01/ PY - 2005 DA - 2005 Feb 01 SP - 404 EP - 5 CY - New York PB - Elsevier Sequoia S.A. VL - 95 IS - 3 SN - 00029149 KW - Medical Sciences--Cardiovascular Diseases KW - Anti-Arrhythmia Agents KW - Amiodarone KW - Cardiac arrhythmia KW - Drug therapy KW - Respiratory diseases KW - Atrial Fibrillation -- complications KW - Humans KW - Chi-Square Distribution KW - Clinical Trials as Topic KW - Aged KW - Male KW - Female KW - Survival Analysis KW - Atrial Fibrillation -- drug therapy KW - Amiodarone -- therapeutic use KW - Lung Diseases -- complications KW - Anti-Arrhythmia Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/230367752?accountid=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=Use+of+amiodarone+for+atrial+fibrillation+in+patients+with+preexisting+pulmonary+disease+in+the+AFFIRM+Study&rft.au=Olshansky%2C+Brian%3BSami%2C+Magdi%3BRubin%2C+Andrew%3BKostis%2C+John%3Bet+al&rft.aulast=Olshansky&rft.aufirst=Brian&rft.date=2005-02-01&rft.volume=95&rft.issue=3&rft.spage=404&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. Feb 1, 2005 N1 - Document feature - references N1 - Last updated - 2013-02-06 N1 - CODEN - AJCDAG ER - TY - JOUR T1 - Decrease in brain serotonin level and short term memory loss in mice: a preliminary study AN - 21045260; 6131852 AB - Most of the information on the effects of benzene center around its hematotoxic and genotoxic effects. However, its effect on central neurotransmitters is inconclusive in terms of cognitive behavior of the host. The present results showed for the first time that chronic exposure to benzene, in drinking water, significantly inhibited serotonin (5-hydroxytryptamine (5-HT)) level in serotonergic neuron rich regions of the murine brain. This was paralleled with loss of short term memory, as evidenced by passive avoidance test, of the benzene treated animals. JF - Environmental Toxicology and Pharmacology AU - Banik, S AU - Lahiri, T AD - Department of Neuroendocrinology, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata 700026, India, sampabanik@yahoo.com Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 367 EP - 370 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 19 IS - 2 SN - 1382-6689, 1382-6689 KW - mice KW - Pollution Abstracts; CSA Neurosciences Abstracts; Toxicology Abstracts KW - Benzene KW - Brain serotonin KW - Memory loss KW - Mice KW - Genotoxicity KW - Brain KW - benzene KW - Short term memory KW - Serotonin KW - Chronic exposure KW - Cognitive ability KW - Neurons KW - Neurotoxicity KW - Neurotransmitters KW - Drinking water KW - Toxicity testing KW - N3 11104:Mammals (except primates) KW - X 24350:Industrial Chemicals KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21045260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Toxicology+and+Pharmacology&rft.atitle=Decrease+in+brain+serotonin+level+and+short+term+memory+loss+in+mice%3A+a+preliminary+study&rft.au=Banik%2C+S%3BLahiri%2C+T&rft.aulast=Banik&rft.aufirst=S&rft.date=2005-02-01&rft.volume=19&rft.issue=2&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Environmental+Toxicology+and+Pharmacology&rft.issn=13826689&rft_id=info:doi/10.1016%2Fj.etap.2004.09.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-05-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Cognitive ability; Chronic exposure; Neurons; Genotoxicity; Neurotoxicity; Brain; Neurotransmitters; Drinking water; Short term memory; Serotonin; Benzene; Mice; Toxicity testing; benzene DO - http://dx.doi.org/10.1016/j.etap.2004.09.002 ER - TY - JOUR T1 - Relative concentrations of organochlorines in adipose tissue and serum among reproductive age women AN - 21034150; 6131884 AB - Much of the available literature focusing on organochlorine exposure and human health effects has relied upon serum for quantifying exposure despite adipose tissue being the purported "gold standard". The accuracy of exposure status is dependent upon serum being a valid and reliable proxy for adipose tissue regardless of compound under study and served as the impetus for study. Serum and omentum fat concentrations for 62 polychlorinated biphenyls (PCBs) and 7 organochlorine pesticides (OCPs) were determined using gas chromatography with electron capture and compared to assess their relative abundance and correlation among 15 women aged 18-40 years undergoing laparoscopy. The relation between concentration in serum and fat was determined by linear regression. Of the 20 organochlorines (OCs) (29%) present in both serum and fat samples, moderate linear correlations (r > 0.6) were observed between lipid-adjusted serum and fat concentrations for PCBs #138, 153, 180, 188, 194, 206, and DDE. Forty-nine OCs were present in adipose samples but measured below the LOD in serum samples. Our findings underscore the potential for discrepant human health results associated with OC exposure on the basis of medium used for quantification purposes, especially for less ubiquitous compounds or when study samples include individuals with relatively low exposures. These data support earlier findings and argue for concerted methodological work aimed at developing standardized laboratory methods for epidemiologic studies. JF - Environmental Toxicology and Pharmacology AU - Whitcomb, B W AU - Schisterman, E F AU - Buck, G M AU - Weiner, J M AU - Greizerstein, H AU - Kostyniak, P J AD - Epidemiology Branch, Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, 6100 Executive Blvd. Rockville, MD 20852, USA, schistee@mail.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 203 EP - 213 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 19 IS - 2 SN - 1382-6689, 1382-6689 KW - Toxicology Abstracts; Pollution Abstracts; Health & Safety Science Abstracts KW - Adipose tissue KW - Endometriosis KW - Limits of detection KW - Organochlorine pesticides KW - Polychlorinated biphenyls KW - GC-ECD, gas chromatography-electron capture detector KW - HAH, halogenated aromatic hydrocarbon KW - IUPAC, International Union of Pure and Applied Chemistry KW - LOD, limit of detection KW - OC, organochlorine KW - OCP, organochlorine pesticide KW - PCB, polychlorinated biphenyl KW - PYE, pyrenylethyl KW - Tissues KW - Age KW - Organochlorine compounds KW - Data processing KW - Laparoscopy KW - DDE KW - Abundance KW - Pesticides (organochlorine) KW - Public health KW - polychlorinated biphenyls KW - Laboratory methods KW - Epidemiology KW - Omentum KW - Gas chromatography KW - Reproduction KW - Females KW - PCB compounds KW - PCB KW - H 12000:Epidemiology and Public Health KW - X 24330:Agrochemicals KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21034150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Toxicology+and+Pharmacology&rft.atitle=Relative+concentrations+of+organochlorines+in+adipose+tissue+and+serum+among+reproductive+age+women&rft.au=Whitcomb%2C+B+W%3BSchisterman%2C+E+F%3BBuck%2C+G+M%3BWeiner%2C+J+M%3BGreizerstein%2C+H%3BKostyniak%2C+P+J&rft.aulast=Whitcomb&rft.aufirst=B&rft.date=2005-02-01&rft.volume=19&rft.issue=2&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Environmental+Toxicology+and+Pharmacology&rft.issn=13826689&rft_id=info:doi/10.1016%2Fj.etap.2004.04.009 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-03-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Age; Data processing; polychlorinated biphenyls; Organochlorine compounds; Omentum; Laparoscopy; Gas chromatography; Abundance; DDE; Pesticides (organochlorine); Adipose tissue; PCB; Tissues; Epidemiology; Laboratory methods; Reproduction; Females; PCB compounds; Public health DO - http://dx.doi.org/10.1016/j.etap.2004.04.009 ER - TY - JOUR T1 - Fallout from Nuclear Weapons Tests and Cancer Risks AN - 20433374; 7606510 AB - Prior to 1950, only limited consideration was given to the health impacts of worldwide dispersion of radioactivity from nuclear testing. But in the following decade, humanity began to significantly change the global radiation environment by testing nuclear weapons in the atmosphere. By the early 1960s, there was no place on Earth where the signature of atmospheric nuclear testing could not be found in soil, water and even polar ice. Cancer investigators who specialize in radiation effects have, over the intervening decades, looked for another signature of nuclear testing--an increase in cancer rates. And although it is difficult to detect such a signal amid the large number of cancers arising from "natural" or "unknown" causes, we and others have found both direct and indirect evidence that radioactive debris dispersed in the atmosphere from testing has adversely affected public health. Frequently, however, there is misunderstanding about the type and magnitude of those effects. Thus today, with heightened fears about the possibilities of nuclear terrorism, it is worthwhile to review what we know about exposure to fallout and its associated cancer risks. JF - American Scientist AU - Simon, S L AU - Bouville, A AU - Land, CE AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd., Bethesda, MD 20892, USA, ssimon@mail.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 48 EP - 57 VL - 94 IS - 1 SN - 0003-0996, 0003-0996 KW - Pollution Abstracts KW - Soil KW - Ice KW - Weapons KW - terrorism KW - Reviews KW - Nuclear weapons KW - Radioactivity KW - Atmosphere KW - Cancer KW - Public health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20433374?accountid=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=American+Scientist&rft.atitle=Fallout+from+Nuclear+Weapons+Tests+and+Cancer+Risks&rft.au=Simon%2C+S+L%3BBouville%2C+A%3BLand%2C+CE&rft.aulast=Simon&rft.aufirst=S&rft.date=2005-02-01&rft.volume=94&rft.issue=1&rft.spage=48&rft.isbn=&rft.btitle=&rft.title=American+Scientist&rft.issn=00030996&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-10-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Soil; Ice; terrorism; Weapons; Reviews; Nuclear weapons; Radioactivity; Atmosphere; Cancer; Public health ER - TY - JOUR T1 - Engineering of a vaccinia virus bacterial artificial chromosome in Escherichia coli by bacteriophage [lambda]-based recombination AN - 19989823; 7924040 AB - The large capacity of vaccinia virus (VAC) for added DNA, cytoplasmic expression and broad host range make it a popular choice for gene delivery, despite the burdensome need for multiple plaque purifications to isolate recombinants. Here we describe how a bacterial artificial chromosome (BAC) containing the entire VAC genome can be engineered in Escherichia coli by homologous recombination using bacteriophage [lambda]-encoded enzymes. The engineered VAC genomes can then be used to produce clonally pure recombinant viruses in mammalian cells without the need for plaque purification. JF - Nature Methods AU - Domi, Arban AU - Moss, Bernard AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Center Drive, Bethesda, Maryland 20892-0445, USA., bmoss@nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 95 EP - 97 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 - 2 SN - 1548-7091, 1548-7091 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Genomes KW - Phages KW - Host range KW - Enzymes KW - Bacterial artificial chromosomes KW - Recombinants KW - Vaccinia virus KW - Mammalian cells KW - Gene transfer KW - Escherichia coli KW - Plaques KW - Purification KW - homologous recombination KW - V 22300:Methods KW - G 07760:Viruses & Phages KW - W 30900:Methods KW - A 01300:Methods KW - J 02300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19989823?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Methods&rft.atitle=Engineering+of+a+vaccinia+virus+bacterial+artificial+chromosome+in+Escherichia+coli+by+bacteriophage+%5Blambda%5D-based+recombination&rft.au=Domi%2C+Arban%3BMoss%2C+Bernard&rft.aulast=Domi&rft.aufirst=Arban&rft.date=2005-02-01&rft.volume=2&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Nature+Methods&rft.issn=15487091&rft_id=info:doi/10.1038%2Fnmeth734 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-01-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Phages; Genomes; Recombinants; Bacterial artificial chromosomes; Host range; Mammalian cells; Gene transfer; Enzymes; Plaques; Purification; homologous recombination; Vaccinia virus; Escherichia coli DO - http://dx.doi.org/10.1038/nmeth734 ER - TY - JOUR T1 - Blood mercury level and blood pressure among US women: results from the National Health and Nutrition Examination Survey 1999-2000 AN - 19934735; 6158595 AB - Exposure to mercury has been linked to elevations in blood pressure (BP), though few data are available. We examined the cross-sectional relationship between blood mercury concentration and BP in a representative US sample of 1240 women, aged 16-49 years, from the National Health and Nutrition Examination Survey 1999-2000. We found no association overall between mercury and BP in multivariate models. We stratified our data by dietary fish intake (presumably reflecting the consumption of long-chain n-3 fatty acids that may reduce BP) resulting in 759 fish consumers and 481 non-fish consumers. We found that for each 1.3 mu g/L (interquartile distance) increase in mercury, systolic BP significantly increased by 1.83mm Hg (95% CI: 0.36, 3.30) among non-fish consumers. A similar pattern was seen for diastolic BP, although it was non-significant. While an adverse effect of mercury exposure at background levels on BP was not present overall, an adverse association was present among non-fish-consuming young and middle-aged women. JF - Environmental Research AU - Vupputuri, S AU - Longnecker, M P AU - Daniels, J L AU - Guo, X 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, USA, suma@email.unc.edu Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 195 EP - 200 VL - 97 IS - 2 SN - 0013-9351, 0013-9351 KW - Sustainability Science Abstracts; Pollution Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts; Human Population KW - Diets KW - Heavy metals KW - Health KW - Nutrition KW - Blood pressure KW - Blood levels KW - USA KW - Exposure KW - Background levels KW - Fatty acids KW - Mercury KW - Consumers KW - Seafood KW - Females KW - Side effects KW - Mercury levels KW - M3 1010:Issues in Sustainable Development KW - M1 125:Population Health-Environment Relations KW - X 24166: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/19934735?accountid=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=Environmental+Research&rft.atitle=Blood+mercury+level+and+blood+pressure+among+US+women%3A+results+from+the+National+Health+and+Nutrition+Examination+Survey+1999-2000&rft.au=Vupputuri%2C+S%3BLongnecker%2C+M+P%3BDaniels%2C+J+L%3BGuo%2C+X%3BSandler%2C+D+P&rft.aulast=Vupputuri&rft.aufirst=S&rft.date=2005-02-01&rft.volume=97&rft.issue=2&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Environmental+Research&rft.issn=00139351&rft_id=info:doi/10.1016%2Fj.envres.2004.05.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-07-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Exposure; Background levels; Fatty acids; Mercury; Health; Consumers; Females; Nutrition; Mercury levels; Side effects; Blood pressure; Blood levels; Diets; Heavy metals; Seafood; USA DO - http://dx.doi.org/10.1016/j.envres.2004.05.001 ER - TY - JOUR T1 - Complex Extracellular Matrices Promote Tissue-Specific Stem Cell Differentiation AN - 19933282; 6177286 AB - Most cells in tissues contact an extracellular matrix on at least one surface. These complex mixtures of interacting proteins provide structural support and biological signals that regulate cell differentiation and may be important for stem cell differentiation. In this study, we have grown a rhesus monkey embryonic stem cell line in the presence of various extracellular matrix components in monolayer, in a NASA-developed rotating wall vessel bioreactor in vitro, and subcutaneously in vivo. We find that individual components of the extracellular matrix, such as laminin-1 or collagen I, do not influence the growth or morphology of the cells. In contrast, a basement membrane extract, Matrigel, containing multiple extracellular matrix components, induces the cells within 4 days to form immature glandular-and tubular-like structures, many of which contain a lumen with polarized epithelium and microvilli. Such structures were seen in vitro when the cells were grown in the bioreactor and when the cells were injected into mice. These tubular-and glandular-like structures were polarized epithelia based on immunostaining for laminin and cytokeratin. The cell aggregates and tumors also contained additional mixed populations of cells, including mesenchymal cells and neuronal cells, based on immunostaining with vimentin and neuronal markers. An extract of cartilage, containing multiple cartilage matrix components, promoted chondrogenesis in vivo where alcian blue- stained cartilage nodules could be observed. Some of these nodules stained with von Kossa, indicating that they had formed calcified cartilage. We conclude that extracellular matrices can promote the differentiation of embryonic stem cells into differentiated cells and structures that are similar to the tissue from which the matrix is derived. Such preprogramming of cell differentiation with extracellular matrices may be useful in targeting stem cells to repair specific damaged organs. JF - Stem Cells AU - Philp, Deborah AU - Chen, Silvia S AU - Fitzgerald, Wendy AU - Orenstein, Jan AU - Margolis, Leonid AU - Kleinman, Hynda K AD - Cell Biology Section, National Institute of Dental and Craniofacial Research, Bethesda, Maryland. NASA/NIH Center for Three Dimensional Tissue Culture, National Institute of Child Health and Human Development, Bethesda, Maryland. George Washington University Medical Center, Washington, DC. Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland, USA Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 288 EP - 296 VL - 23 IS - 2 SN - 1066-5099, 1066-5099 KW - Biotechnology and Bioengineering Abstracts KW - Laminin KW - Cartilage KW - Tumors KW - Vimentin KW - Nodules KW - Stem cells KW - Basement membranes KW - Embryo cells KW - Bioreactors KW - Extracellular matrix KW - Macaca mulatta KW - Epithelium KW - Mesenchyme KW - Collagen (type I) KW - Cytokeratin KW - Chondrogenesis KW - W 30950:Waste Treatment & Pollution Clean-up UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19933282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+Cells&rft.atitle=Complex+Extracellular+Matrices+Promote+Tissue-Specific+Stem+Cell+Differentiation&rft.au=Philp%2C+Deborah%3BChen%2C+Silvia+S%3BFitzgerald%2C+Wendy%3BOrenstein%2C+Jan%3BMargolis%2C+Leonid%3BKleinman%2C+Hynda+K&rft.aulast=Philp&rft.aufirst=Deborah&rft.date=2005-02-01&rft.volume=23&rft.issue=2&rft.spage=288&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-07-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Laminin; Cartilage; Tumors; Nodules; Vimentin; Stem cells; Embryo cells; Basement membranes; Extracellular matrix; Bioreactors; Epithelium; Mesenchyme; Collagen (type I); Chondrogenesis; Cytokeratin; Macaca mulatta ER - TY - JOUR T1 - Modulation of p-Glycoprotein Transport Function at the Blood-Brain Barrier AN - 19807726; 6172535 AB - The central nervous system (CNS) effects of many therapeutic drugs are blunted because of restricted entry into the brain. The basis for this poor permeability is the brain capillary endothelium, which comprises the blood-brain barrier. This tissue exhibits very low paracellular (tight-junctional) permeability and expresses potent, multispecific, drug export pumps. Together, these combine to limit use of pharmacotherapy to treat CNS disorders such as brain cancer and bacterial or viral infections. Of all the xenobiotic efflux pumps highly expressed in brain capillary endothelial cells, p-glycoprotein handles the largest fraction of commonly prescribed drugs and thus is an obvious target for manipulation. Here we review recent studies focused on understanding the mechanisms by which p-glycoprotein activity in the blood-brain barrier can be modulated. These include (i) direct inhibition by specific competitors, (ii) functional modulation, and (iii) transcriptional modulation. Each has the potential to specifically reduce p-glycoprotein function and thus selectively increase brain permeability of p-glycoprotein substrates. JF - Experimental Biology and Medicine AU - Bauer, Bjoern AU - Hartz, Anika MS AU - Fricker, Gert AU - Miller, David S AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 118 EP - 127 PB - Society for Experimental Biology and Medicine, 195 W. Spring Valley Avenue Maywood NJ 07607-1727 USA, [mailto:sebm@inch.com], [URL:http://www.sebm.org/] VL - 230 IS - 2 SN - 1535-3699, 1535-3699 KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; CSA Neurosciences Abstracts KW - Central nervous system KW - Blood-brain barrier KW - Brain KW - Membrane permeability KW - Transcription KW - Infection KW - Cancer KW - Endothelial cells KW - Permeability KW - P-Glycoprotein KW - Reviews KW - Endothelium KW - Drugs KW - N3 11028:Neuropharmacology & toxicology KW - V 22340:Antiviral Agents KW - J 02490:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19807726?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+Biology+and+Medicine&rft.atitle=Modulation+of+p-Glycoprotein+Transport+Function+at+the+Blood-Brain+Barrier&rft.au=Bauer%2C+Bjoern%3BHartz%2C+Anika+MS%3BFricker%2C+Gert%3BMiller%2C+David+S&rft.aulast=Bauer&rft.aufirst=Bjoern&rft.date=2005-02-01&rft.volume=230&rft.issue=2&rft.spage=118&rft.isbn=&rft.btitle=&rft.title=Experimental+Biology+and+Medicine&rft.issn=15353699&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-10-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Central nervous system; Blood-brain barrier; Brain; Transcription; Membrane permeability; Infection; Cancer; Endothelial cells; Permeability; P-Glycoprotein; Reviews; Endothelium; Drugs ER - TY - JOUR T1 - Methodologic Implications of the Precautionary Principle: Causal Criteria AN - 19605641; 7322331 AB - Applying the Precautionary Principle to public health requires a re- evaluation of the methods of inference currently used to make claims about disease causation from epidemiologic and other forms of scientific evidence. In current thinking, a well-established, near-certain causal relationship implies highly consistent statistically significant results across many different studies, large relative risk estimates, extensive understanding of biological mechanisms and dose-response relationships, positive prevention trial results, a clear temporal relationship between cause and effect, and other conditions spelled out in terms of the widely-used causal criteria. The Precautionary Principle, however, states that preventive measures are to be taken when cause and effect relationships are not fully established scientifically. What evidentiary conditions, as reflected in the causal criteria, will be certain enough to warrant precautionary preventive action? This paper argues that minimum evidentiary requirements for causation need to be articulated if the Precautionary Principle is to be successfully incorporated into public health practice. Two precautionary changes to criteria-based methods of causal inference are examined: reducing the number of criteria and weakening the rules of inference accompanying the criteria. Such changes point in the direction of identifying minimum evidentiary conditions, but would be premature without better understanding how well current methods of causal inference work. JF - Human and Ecological Risk Assessment AU - Weed, Douglas AD - Division of Cancer Prevention, National Cancer Institute, Rockville, MD, USA Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 107 EP - 113 PB - CRC Press LLC, 2000 Corporate Blvd., NW Boca Raton FL 33431 USA, [mailto:journals@crcpress.com], [URL:http://www.crcpress.com] VL - 11 IS - 1 SN - 1080-7039, 1080-7039 KW - Risk Abstracts KW - causation KW - epidemiology KW - inference KW - Precautionary Principle KW - theory KW - precautionary principle KW - Dose-response effects KW - prevention KW - Public health KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19605641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+and+Ecological+Risk+Assessment&rft.atitle=Methodologic+Implications+of+the+Precautionary+Principle%3A+Causal+Criteria&rft.au=Weed%2C+Douglas&rft.aulast=Weed&rft.aufirst=Douglas&rft.date=2005-02-01&rft.volume=11&rft.issue=1&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Human+and+Ecological+Risk+Assessment&rft.issn=10807039&rft_id=info:doi/10.1080%2F10807030590919936 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-04-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - precautionary principle; Dose-response effects; prevention; Public health DO - http://dx.doi.org/10.1080/10807030590919936 ER - TY - JOUR T1 - Multidisciplinary Research: Strategies for Assessing Chemical Mixtures to Reduce Risk of Exposure and Disease AN - 19603832; 7322334 AB - The Precautionary Principle is founded on the use of comprehensive, coordinated research to protect human health in the face of uncertain risks. Research directed at key data gaps may significantly reduce the uncertainty underlying the complexities of assessing risk to mixtures. The National Institute of Environmental Health Sciences (NIEHS) has taken a leadership role in building the scientific infrastructure to address these uncertainties. The challenge is to incorporate the objectives as defined by the Precautionary Principle with the knowledge gained in understanding the multifactorial nature of gene-environment interactions. Through efforts such as the National Center for Toxicogenomics, the National Toxicology Program, and the Superfund Basic Research Program, NIEHS is translating research findings into public health prevention strategies using a 3-pronged approach: (1) identify/evaluate key deviations from additivity for mixtures; (2) develop/apply/link advanced technologies and bioinformatics to quantitative tools for an integrated science- based approach to chemical mixtures; (3) translate/disseminate these technologies into useable, practical means to reduce exposure and the risk of disease. Preventing adverse health effects from environmental exposures requires translation of research findings to affected communities and must include a high level of public involvement. Integrating these approaches are necessary to advance understanding of the health relevance of exposure to mixtures. JF - Human and Ecological Risk Assessment AU - Suk, William AU - Olden, Kenneth AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 141 EP - 151 PB - CRC Press LLC, 2000 Corporate Blvd., NW Boca Raton FL 33431 USA, [mailto:journals@crcpress.com], [URL:http://www.crcpress.com] VL - 11 IS - 1 SN - 1080-7039, 1080-7039 KW - Pollution Abstracts; Sustainability Science Abstracts; Risk Abstracts; Health & Safety Science Abstracts KW - multidisciplinary KW - chemical mixtures KW - Precautionary Principle KW - Chemicals KW - Precautionary principle KW - Environmental health KW - Bioinformatics KW - Toxicity KW - Diseases KW - M3 1010:Issues in Sustainable Development 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/19603832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+and+Ecological+Risk+Assessment&rft.atitle=Multidisciplinary+Research%3A+Strategies+for+Assessing+Chemical+Mixtures+to+Reduce+Risk+of+Exposure+and+Disease&rft.au=Suk%2C+William%3BOlden%2C+Kenneth&rft.aulast=Suk&rft.aufirst=William&rft.date=2005-02-01&rft.volume=11&rft.issue=1&rft.spage=141&rft.isbn=&rft.btitle=&rft.title=Human+and+Ecological+Risk+Assessment&rft.issn=10807039&rft_id=info:doi/10.1080%2F10807030590919963 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-04-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Chemicals; Precautionary principle; Environmental health; Diseases; Toxicity; Bioinformatics DO - http://dx.doi.org/10.1080/10807030590919963 ER - TY - JOUR T1 - Just Get Out the Door! Importance of Walking Outside the Home for Maintaining Mobility: Findings from the Women's Health and Aging Study AN - 19430082; 6238217 AB - Objectives: To determine the association between volitional walking behavior and change in walking ability and lower extremity function over 1 year in functionally limited older women. Design: Longitudinal cohort study. Setting: Data were collected in participant's homes in Baltimore, Maryland. Participants: One thousand two cognitively intact community-resident female Medicare beneficiaries aged 65 and older enrolled in the Women's Health and Aging Study. Measurements: Reported walking behavior and change in reported walking difficulty, usual and rapid gait speed, and lower extremity physical performance score over 1 year. Results: Of 800 functionally limited women who could walk unassisted at baseline and were alive and contacted 1 year later, 226 (28%) walked regularly, at least eight blocks per week. These women exhibited better health and functioning than nonwalkers (e.g., lower prevalence of depressive and fatigue symptoms and cardiovascular disease and higher mean ankle-arm index, forced expiratory volume in the first second, and gait speed). One year later, independent of initial functional status, social-psychological and behavioral factors, and health conditions, walkers were 1.8 times (95% confidence interval=1.2-2.7; P=.002) more likely to maintain reported walking ability and showed less decline in customary walking speed (0.009 m-s vs -0.070 m-s; P=.001) and functional performance score (-0.17 vs -0.73; P=.01) than women who walked less than eight blocks. Conclusion: The strength, consistency, and specificity of the association between walking behavior and maintenance of mobility provide strong evidence that even a small amount of regular walking can confer short-term protection from further mobility loss in functionally limited women. The observation that most women capable of walking at least eight blocks per week were not doing so indicates the need to get more women 'out the door' and to encourage those who walk a little to walk a little more. JF - Journal of the American Geriatrics Society AU - Simonsick, Eleanor M AU - Guralnik, Jack M AU - Volpato, Stefano AU - Balfour, Jennifer AU - Fried, Linda P AD - Dr. Simonsick, National Institute on Aging-ASTRA, Harbor Hospital, 5th Floor, 3001 South Hanover Street, Baltimore, MD 21225, simonsickel@grc.nia.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 198 EP - 203 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 53 IS - 2 SN - 0002-8614, 0002-8614 KW - Physical Education Index KW - Confidence KW - Measurement KW - Home KW - Fatigue KW - Specificity KW - Women KW - Gerontology KW - Medicare KW - Walking KW - Observation KW - Legs KW - Health KW - Movement KW - Speed KW - Strength KW - Behavior KW - Geriatrics KW - Cardiorespiratory KW - Performance KW - Diseases KW - Gait KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19430082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Geriatrics+Society&rft.atitle=Just+Get+Out+the+Door%21+Importance+of+Walking+Outside+the+Home+for+Maintaining+Mobility%3A+Findings+from+the+Women%27s+Health+and+Aging+Study&rft.au=Simonsick%2C+Eleanor+M%3BGuralnik%2C+Jack+M%3BVolpato%2C+Stefano%3BBalfour%2C+Jennifer%3BFried%2C+Linda+P&rft.aulast=Simonsick&rft.aufirst=Eleanor&rft.date=2005-02-01&rft.volume=53&rft.issue=2&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Geriatrics+Society&rft.issn=00028614&rft_id=info:doi/10.1111%2Fj.1532-5415.2005.53103.x LA - English DB - Physical Education Index N1 - Date revised - 2006-12-01 N1 - SuppNotes - Figures, 3; tables, 3; references, 38. N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Confidence; Measurement; Fatigue; Home; Specificity; Women; Medicare; Gerontology; Walking; Health; Legs; Observation; Movement; Strength; Speed; Behavior; Geriatrics; Cardiorespiratory; Diseases; Performance; Gait DO - http://dx.doi.org/10.1111/j.1532-5415.2005.53103.x ER - TY - JOUR T1 - Sizing it up: Cellular MRI using micron-sized iron oxide particles AN - 19410276; 6496839 AB - There is rapidly increasing interest in the use of MRI to track cell migration in intact animals. Currently, cell labeling is usually accomplished by endocytosis of nanometer-sized, dextran-coated iron oxide particles. The limitations of using nanometer-sized particles, however, are that millions of particles are required to achieve sufficient contrast, the label can be diluted beyond observability by cell division, and the label is biodegradable. These problems make it difficult to label cells other than macrophages in vivo, and to conduct long-term engraftment studies. It was recently demonstrated that micron-sized iron oxide particles (MPIOs) can be taken up by a number of cell types. In this study we examined the MRI properties of single MPIOs with sizes of 0.96, 1.63, 2.79, 4.50, and 5.80 mu m. Furthermore, the capacity of cells to endocytose these MPIOs was investigated, and the MRI properties of the labeled cells at 7.0 and 11.7 Tesla were measured as a function of image resolution and echo time (TE). Cells labeled with MPIOs generally contained iron levels of similar to 100 pg, which is approximately threefold higher than those obtained with the best strategies to label cells using nanometer-sized particles. On occasion, some cells had levels as high as similar to 400 pg. We demonstrate that these large particles and the cells labeled with them can be detected by spin echo (SE)-based imaging methods. These measurements indicate that MPIOs should be useful for improving cell tracking by MRI. JF - Magnetic Resonance in Medicine AU - Shapiro, Erik M AU - Skrtic, Stanko AU - Koretsky, Alan P AD - National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA, ShapiroE@ninds.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 329 EP - 338 PB - John Wiley & Sons, Ltd. VL - 53 IS - 2 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts KW - Macrophages KW - Endocytosis KW - Cell division KW - iron oxides KW - Magnetic resonance imaging KW - Image processing KW - N.M.R. KW - Cell migration KW - Iron KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19410276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Sizing+it+up%3A+Cellular+MRI+using+micron-sized+iron+oxide+particles&rft.au=Shapiro%2C+Erik+M%3BSkrtic%2C+Stanko%3BKoretsky%2C+Alan+P&rft.aulast=Shapiro&rft.aufirst=Erik&rft.date=2005-02-01&rft.volume=53&rft.issue=2&rft.spage=329&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20342 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; iron oxides; Iron; N.M.R.; Cell division; Cell migration; Macrophages; Image processing; Endocytosis DO - http://dx.doi.org/10.1002/mrm.20342 ER - TY - JOUR T1 - A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells AN - 18010590; 5977962 AB - The utilization of adult stem cells in tissue engineering is a promising solution to the problem of tissue or organ shortage. Adult bone marrow derived mesenchymal stem cells (MSCs) are undifferentiated, multipotential cells which are capable of giving rise to chondrocytes when maintained in a three- dimensional culture and treated with members of the transforming growth factor- beta (TGF- beta ) family of growth factors. In this study, we fabricated a nanofibrous scaffold (NFS) made of a synthetic biodegradable polymer, poly( epsilon -caprolactone) (PCL), and examined its ability to support in vitro chondrogenesis of MSCs. The electrospun PCL porous scaffold was constructed of uniform, randomly oriented nanofibers with a diameter of 700 nm, and structural integrity of this scaffold was maintained over a 21-day culture period. MSCs cultured in NFSs in the presence of TGF- beta 1 differentiated to a chondrocytic phenotype, as evidenced by chondrocyte-specific gene expression and synthesis of cartilage-associated extracellular matrix (ECM) proteins. The level of chondrogenesis observed in MSCs seeded within NFSs was comparable to that observed for MSCs maintained as cell aggregates or pellets, a widely used culture protocol for studying chondrogenesis of MSCs in vitro. Due to the physical nature and improved mechanical properties of NFSs, particularly in comparison to cell pellets, the findings reported here suggest that the PCL NFS is a practical carrier for MSC transplantation, and represents a candidate scaffold for cell-based tissue engineering approaches to cartilage repair. JF - Biomaterials AU - Li, W-J AU - Tuli, R AU - Okafor, C AU - Derfoul, A AU - Danielson, K G AU - Hall, D J AU - Tuan, R S AD - Department of Health and Human Services, Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, MD 20892, USA, tuanr@mail.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 599 EP - 609 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 26 IS - 6 SN - 0142-9612, 0142-9612 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Stem cells KW - Extracellular matrix KW - Cartilage KW - Chondrocytes KW - Growth factors KW - Tissue engineering KW - Mesenchyme KW - scaffolds 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/18010590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+three-dimensional+nanofibrous+scaffold+for+cartilage+tissue+engineering+using+human+mesenchymal+stem+cells&rft.au=Li%2C+W-J%3BTuli%2C+R%3BOkafor%2C+C%3BDerfoul%2C+A%3BDanielson%2C+K+G%3BHall%2C+D+J%3BTuan%2C+R+S&rft.aulast=Li&rft.aufirst=W-J&rft.date=2005-02-01&rft.volume=26&rft.issue=6&rft.spage=599&rft.isbn=&rft.btitle=&rft.title=Biomaterials&rft.issn=01429612&rft_id=info:doi/10.1016%2Fj.biomaterials.2004.03.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mesenchyme; Stem cells; Cartilage; Tissue engineering; Growth factors; Chondrocytes; scaffolds; Extracellular matrix DO - http://dx.doi.org/10.1016/j.biomaterials.2004.03.005 ER - TY - JOUR T1 - Prevention Interventions With Persons Living With HIV/AIDS: State of the Science and Future Directions AN - 17835799; 6206344 AB - The National Institutes of Health (NIH/NIMH), the Centers for Disease Control and Prevention (CDC), and the HIV/AIDS Bureau of the Health Resources and Services Administration (HRSA) support the CDC's Serostatus Approach to Fighting the HIV Epidemic. One aim of the strategy is to help individuals living with HIV (and their partners) adopt and sustain HIV and STD risk reduction, treatment adherence, and effective strategies for coping with HIV/AIDS. Efficacious interventions are needed by community organizations and clinics that provide evidence-based services. To expedite translation from research to practice, we convened scientist-practitioners, HIV treatment and prevention providers, and community/consumer members. In this article, we include an overview of prevention trials with HIV-positive persons presented at the meeting, discuss strengths and limitations, recommendations for future research, and discuss sponsoring agencies' plans for advancing prevention tailored for persons living with HIV. JF - AIDS Education and Prevention AU - Gordon, C M AU - Forsyth, AD AU - Stall, R AU - Cheever, L W AD - Secondary HIV Prevention and Treatment Adherence, NIMH, Center for Mental Health Research on AIDS, 6001 Executive Blvd. (Room 6204), Bethesda, MD 20892, USA, cgordon1@mail.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 6 EP - 20 VL - 17 SN - 0899-9546, 0899-9546 KW - HIV KW - Health & Safety Science Abstracts; Risk Abstracts; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Epidemics KW - Sexually-transmitted diseases KW - Disease control KW - disease control KW - risk reduction KW - Education KW - Human immunodeficiency virus KW - Reviews KW - prevention KW - Consumers KW - sexually transmitted diseases KW - H 11000:Diseases/Injuries/Trauma KW - V 22006:AIDS: Other aspects KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17835799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+Education+and+Prevention&rft.atitle=Prevention+Interventions+With+Persons+Living+With+HIV%2FAIDS%3A+State+of+the+Science+and+Future+Directions&rft.au=Gordon%2C+C+M%3BForsyth%2C+AD%3BStall%2C+R%3BCheever%2C+L+W&rft.aulast=Gordon&rft.aufirst=C&rft.date=2005-02-01&rft.volume=17&rft.issue=&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=AIDS+Education+and+Prevention&rft.issn=08999546&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Acquired immune deficiency syndrome; Epidemics; Sexually-transmitted diseases; Reviews; Disease control; Consumers; risk reduction; Education; prevention; disease control; sexually transmitted diseases; Human immunodeficiency virus ER - TY - JOUR T1 - Primary Culture of Polarized Human Salivary Epithelial Cells for Use in Developing an Artificial Salivary Gland AN - 17808662; 6199890 AB - Therapeutic irradiation for head and neck cancer, and the autoimmune disease Sjoegren's syndrome, lead to loss of salivary parenchyma. They are the two main causes of irreversible salivary gland hypofunction. Such patients cannot produce adequate levels of saliva, leading to considerable morbidity. We are working to develop an artificial salivary gland for such patients. A major problem in this endeavor has been the difficulty in obtaining a suitable autologous cellular component. This article describes a method of culturing and expanding primary salivary cells obtained from human submandibular glands (huSMGs) that is serum free and yields cells that are epithelial in nature. These include morphological (light and transmission electron microscopy [TEM]), protein expression (immunologically positive for ZO-1, claudin-1, and E-cadherin), and functional evidence. Under confocal microscopy, huSMG cells show polarization and appropriately localize tight junction proteins. TEM micrographs show an absence of dense core granules, but confirm the presence of tight and intermediate junctions and desmosomes between the cells. Functional assays showed that huSMG cells have high transepithelial electrical resistance and low rates of paracellular fluid movement. Additionally, huSMG cells show a normal karyotype without any morphological or numerical abnormalities, and most closely resemble striated and excretory duct cells in appearance. We conclude that this culture method for obtaining autologous human salivary cells should be useful in developing an artificial salivary gland. JF - Tissue Engineering AU - Tran, S D AU - Wang, J AU - Bandyopadhyay, B C AU - Redman, R S AU - Dutra, A AU - Pak, E AU - Swaim, W D AU - Gerstenhaber, JA AU - Bryant, J M AU - Zheng, C AU - Goldsmith, C M AU - Kok, M R AU - Wellner, R B AU - Baum, B J AD - GTTB, NIDCR, NIH, Bldg. 10, Rm. 1N113, MSC-1190, Bethesda, MD 20892, USA, bbaum@dir.nidcr.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 172 EP - 181 VL - 11 IS - 1-2 SN - 1076-3279, 1076-3279 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Epithelial cells KW - Tight junctions KW - Transmission electron microscopy KW - Autoimmune diseases KW - Cell culture KW - Salivary gland KW - Sjogren's syndrome KW - Head and neck cancer KW - Submandibular gland KW - Polarization KW - Confocal microscopy KW - Saliva 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/17808662?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Primary+Culture+of+Polarized+Human+Salivary+Epithelial+Cells+for+Use+in+Developing+an+Artificial+Salivary+Gland&rft.au=Tran%2C+S+D%3BWang%2C+J%3BBandyopadhyay%2C+B+C%3BRedman%2C+R+S%3BDutra%2C+A%3BPak%2C+E%3BSwaim%2C+W+D%3BGerstenhaber%2C+JA%3BBryant%2C+J+M%3BZheng%2C+C%3BGoldsmith%2C+C+M%3BKok%2C+M+R%3BWellner%2C+R+B%3BBaum%2C+B+J&rft.aulast=Tran&rft.aufirst=S&rft.date=2005-02-01&rft.volume=11&rft.issue=1-2&rft.spage=172&rft.isbn=&rft.btitle=&rft.title=Tissue+Engineering&rft.issn=10763279&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Salivary gland; Cell culture; Epithelial cells; Tight junctions; Saliva; Confocal microscopy; Transmission electron microscopy; Polarization; Autoimmune diseases; Submandibular gland; Head and neck cancer; Sjogren's syndrome ER - TY - JOUR T1 - Let it flow but don't let go: saliva and colonization AN - 17808394; 6207710 AB - After our teeth are cleaned, bacteria reappear on the tooth enamel in the form of mixed-species communities, which are again disrupted when we next floss and brush. This article focuses on biofilm formation during the interval between typical personal oral hygiene procedures, roughly 8-12 hours. Saliva bathes the tooth surfaces carrying bacteria to and from the enamel. To be successful in the first step of colonization of the tooth, bacteria must possess constitutively expressed cell-surface-associated polymers whose function is to recognize and bind structurally complementary molecules in a pellicle formed by saliva on the enamel surface. Human oral bacteria also possess cell-surface-associated polymers that mediate cell-cell binding between genetically distinct cells. This cell-cell interaction is called coaggregation. Oral bacteria display a propensity to coaggregate and each strain coaggregates with a specific set of partner strains. Consequently, the potential exists for a network of coaggregation-mediated multi-species communities. Initial adherence of bacteria to the saliva-coated enamel substratum, coaggregation and cellular growth are considered the three primary mechanisms integral to bacterial colonization of a clean enamel surface. JF - Microbiology Today AU - Kolenbrander, P E AU - Palmer, RJ Jr AU - Rickard, AH AU - Jakubovics, N S AU - Diaz, P I AD - National Institutes of Health, Building 30, Room 310, 30 Convent Drive MSC4350, Bethesda, MD 20892-4350, USA, pkolenbrander@dir.nidcr.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 11 EP - 13 VL - 32 SN - 1464-0570, 1464-0570 KW - Microbiology Abstracts B: Bacteriology KW - Teeth KW - Colonization KW - Enamel KW - Oral hygiene KW - Adherence KW - Cell interaction KW - Pellicle KW - Biofilms KW - Saliva KW - Dental enamel KW - J 02841:Microflora UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17808394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Today&rft.atitle=Let+it+flow+but+don%27t+let+go%3A+saliva+and+colonization&rft.au=Kolenbrander%2C+P+E%3BPalmer%2C+RJ+Jr%3BRickard%2C+AH%3BJakubovics%2C+N+S%3BDiaz%2C+P+I&rft.aulast=Kolenbrander&rft.aufirst=P&rft.date=2005-02-01&rft.volume=32&rft.issue=&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Microbiology+Today&rft.issn=14640570&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 - Dental enamel; Teeth; Colonization; Cell interaction; Adherence; Saliva; Oral hygiene; Enamel; Pellicle; Biofilms ER - TY - JOUR T1 - Targeting Tumor Angiogenesis with Adenovirus-Delivered Anti-Tie-2 Intrabody AN - 17804940; 6168076 AB - Inhibition of tumor angiogenesis is a promising approach for cancer therapy. As an endothelial cell-specific receptor kinase expressed almost exclusively on the surface of vascular endothelium, Tie-2 has an important role in tumor angiogenesis. To explore the therapeutic potential of blocking Tie-2 receptor- interaction pathway, an adenoviral vector was used to deliver a recombinant single-chain antibody fragment rabbit intrabody (pAd-2S03) capable of inhibition of both mouse and human Tie-2 surface expression. pAd-2S03 was given to mice with well-established primary tumors, either a human Kaposi's sarcoma (SLK) or a human colon carcinoma (SW1222). The intrabody significantly inhibited growth of both tumors (75% and 63%, respectively) when compared with pAd-GFP control- treated tumors (P 87% in both tumor models when compared with control-treated tumors (P < 0.01). In contrast, human Tie-2-monospecific pAd-1S05 intrabody did not affect the growth of tumors, indicating that the antitumor effect of pAd- 2S03 was due to the inhibition of tumor angiogenesis in these murine models. Our results show that the Tie-2 receptor pathway is essential for both SLK sarcoma and SW1222 colon carcinoma xenograft growth. The present study shows the potential utility of antiangiogenic agents that target the endothelium-specific receptor Tie-2 for down-regulation or genetic deletion. JF - Cancer Research AU - Popkov, Mikhail AU - Jendreyko, Nina AU - Mcgavern, Dorian B AU - Rader, Christoph AU - Barbas, Carlos F AD - Department of Molecular Biology and Skaggs Institute for Chemical Biology and Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California and Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland Y1 - 2005/02/01/ PY - 2005 DA - 2005 Feb 01 SP - 972 EP - 981 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 65 IS - 3 SN - 0008-5472, 0008-5472 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - intrabodies KW - antiangiogenic agents KW - Gene therapy KW - Angiogenesis KW - Adenovirus KW - Expression vectors KW - Kaposi's sarcoma KW - Endothelium KW - Sarcoma KW - Colorectal carcinoma KW - Vascular system KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17804940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Targeting+Tumor+Angiogenesis+with+Adenovirus-Delivered+Anti-Tie-2+Intrabody&rft.au=Popkov%2C+Mikhail%3BJendreyko%2C+Nina%3BMcgavern%2C+Dorian+B%3BRader%2C+Christoph%3BBarbas%2C+Carlos+F&rft.aulast=Popkov&rft.aufirst=Mikhail&rft.date=2005-02-01&rft.volume=65&rft.issue=3&rft.spage=972&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 - Adenovirus; intrabodies; Angiogenesis; Colorectal carcinoma; Kaposi's sarcoma; Gene therapy; Expression vectors; antiangiogenic agents; Endothelium; Vascular system; Sarcoma ER - TY - JOUR T1 - Maternal serum level of the DDT metabolite DDE in relation to fetal loss in previous pregnancies AN - 17800150; 6157771 AB - Use of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) continues in about 25 countries. This use has been justified partly by the belief that it has no adverse consequences on human health. Evidence has been increasing, however, for adverse reproductive effects of DDT, but additional data are needed. Pregnant women who enrolled in the Collaborative Perinatal Project (United States, 1959-1965) were asked about their previous pregnancy history; blood samples were drawn and the serum frozen. In 1997-1999, the sera of 1717 of these women who had previous pregnancies were analyzed for 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), the major breakdown product of DDT. The odds of previous fetal loss was examined in relation to DDE level in logistic regression models. Compared with women whose DDE level was <15 mu g/L, the adjusted odds ratios of fetal loss according to category of DDE were as follows: 15-29 mu g/L, 1.1; 30-44 mu g/L, 1.4; 45-59 mu g/L, 1.6; and 60+ mu g/L, 1.2. The adjusted odds ratio per 60 mu g/L increase was 1.4 (95% confidence interval 1.1-1.6). The results were consistent with an adverse effect of DDE on fetal loss, but were inconclusive owing to the possibility that previous pregnancies ending in fetal loss decreased serum DDE levels less than did those carried to term. JF - Environmental Research AU - Longnecker, M P AU - Klebanoff, MA AU - Dunson, D B AU - Guo, X AU - Chen, Z AU - Zhou, H AU - Brock, J W AD - Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233 MD A3-05, 27709, Research Triangle Park, NC, USA Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 127 EP - 133 VL - 97 IS - 2 SN - 0013-9351, 0013-9351 KW - Toxicology Abstracts KW - Serum levels KW - DDE KW - DDT KW - Metabolites KW - Fetuses KW - Side effects KW - Pregnancy KW - X 24133:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17800150?accountid=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+Research&rft.atitle=Maternal+serum+level+of+the+DDT+metabolite+DDE+in+relation+to+fetal+loss+in+previous+pregnancies&rft.au=Longnecker%2C+M+P%3BKlebanoff%2C+MA%3BDunson%2C+D+B%3BGuo%2C+X%3BChen%2C+Z%3BZhou%2C+H%3BBrock%2C+J+W&rft.aulast=Longnecker&rft.aufirst=M&rft.date=2005-02-01&rft.volume=97&rft.issue=2&rft.spage=127&rft.isbn=&rft.btitle=&rft.title=Environmental+Research&rft.issn=00139351&rft_id=info:doi/10.1016%2FS0013-9351%2803%2900108-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Serum levels; DDT; DDE; Metabolites; Side effects; Fetuses; Pregnancy DO - http://dx.doi.org/10.1016/S0013-9351(03)00108-7 ER - TY - JOUR T1 - Late Treatment with a Protective Antigen-Directed Monoclonal Antibody Improves Hemodynamic Function and Survival in a Lethal Toxin-Infused Rat Model of Anthrax Sepsis AN - 17799518; 6146850 AB - Background. In animal models, treatment with 5H3, a fully human protective antigen-directed monoclonal antibody (PA-MAb), improved survival when administered close to the time of Bacillus anthracis lethal toxin (LeTx) bolus or live bacterial challenge. However, treatment with PA-MAb would be most valuable clinically if it were beneficial even when administered after the onset of shock and lethality due to LeTx. Methods. We investigated the effects of PA-MAb versus placebo administered in rats (n = 324) at the time of or 3, 6, 9, or 12 h after the initiation of a 24-h LeTx infusion. Results. In rats receiving placebo, mean arterial blood pressure (MBP) and heart rate (HR) were decreased in nonsurvivors, compared with those in survivors, at 6 h and then worsened further, with lethality first evident at 8 h (median, 16 h; range, 8-152 h). At each treatment time, survival rates were greater for PA-MAb than for placebo, although improvement was decreased at later treatment times (P = .001, for the effect of time). Compared with placebo, PA-MAb significantly increased MBP during the 12 h after the initiation of treatment, but the increase was greatest for treatment at 3 h; similarly, PA-MAb significantly increased HR at all treatment times. Conclusion. In this rat model, improvements in outcome due to PA-MAb were significant when it was administered up to 6 h (and approached significance when administered up to 12 h) after initial exposure to LeTx. Clinically, PA-MAb may be beneficial even when administered after the onset of shock and lethality due to LeTx. JF - Journal of Infectious Diseases AU - Cui, X AU - Li, Y AU - Moayeri, M AU - Choi, G H AU - Subramanian, G M AU - Li, X AU - Haley, M AU - Fitz, Y AU - Feng, J AU - Banks, S M AU - Leppla, SH AU - Eichacker, P Q AD - Critical Care Medicine Department, Clinical Center, and National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA Y1 - 2005/02/01/ PY - 2005 DA - 2005 Feb 01 SP - 422 EP - 434 VL - 191 IS - 3 SN - 0022-1899, 0022-1899 KW - rats KW - Microbiology Abstracts B: Bacteriology KW - Monoclonal antibodies KW - Heart rate KW - Animal models KW - Hemodynamics KW - Survival KW - Bacillus anthracis KW - Blood pressure KW - Toxins KW - Sepsis KW - Antigens KW - Lethality KW - Shock KW - Anthrax KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17799518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Late+Treatment+with+a+Protective+Antigen-Directed+Monoclonal+Antibody+Improves+Hemodynamic+Function+and+Survival+in+a+Lethal+Toxin-Infused+Rat+Model+of+Anthrax+Sepsis&rft.au=Cui%2C+X%3BLi%2C+Y%3BMoayeri%2C+M%3BChoi%2C+G+H%3BSubramanian%2C+G+M%3BLi%2C+X%3BHaley%2C+M%3BFitz%2C+Y%3BFeng%2C+J%3BBanks%2C+S+M%3BLeppla%2C+SH%3BEichacker%2C+P+Q&rft.aulast=Cui&rft.aufirst=X&rft.date=2005-02-01&rft.volume=191&rft.issue=3&rft.spage=422&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 - Bacillus anthracis; Survival; Lethality; Antigens; Animal models; Monoclonal antibodies; Shock; Heart rate; Hemodynamics; Toxins; Blood pressure; Anthrax; Sepsis ER - TY - JOUR T1 - Capped RNA Transcripts of Full-Length cDNA Clones of Swine Hepatitis E Virus Are Replication Competent When Transfected into Huh7 Cells and Infectious When Intrahepatically Inoculated into Pigs AN - 17772309; 6171799 AB - Swine hepatitis E virus (swine HEV), the first animal strain of HEV to be isolated, is a zoonotic agent. We report here the construction and in vitro and in vivo characterizations of infectious cDNA clones of swine HEV. Eight overlapping fragments spanning the entire genome were amplified by reverse transcription-PCR and assembled into a full-length cDNA clone, clone C, which contained 14 mutations compared to the consensus sequence of swine HEV. RNA transcripts from clone C were not infectious, as determined by intrahepatic inoculation into pigs and by in vitro transfection of Huh7 cells. Multiple site- based site-directed mutagenesis was performed to generate three new cDNA clones (pSHEV-1, pSHEV-2, and pSHEV-3) which differed from each other. The transfection of capped RNA transcripts into human liver Huh7 cells resulted in the synthesis of both ORF2 capsid and ORF3 proteins, indicating that the cDNA clones were replication competent. Each of the three clones resulted in active swine HEV infections after the intrahepatic inoculation of pigs with capped RNA transcripts. The patterns of seroconversion, viremia, and fecal virus shedding for pigs inoculated with RNA transcripts from clones pSHEV-2 and pSHEV-3 were similar to each other and to those for pigs inoculated with wild-type swine HEV, suggesting that the nucleotide differences between these two cDNA clones were not critical for replication. Pigs inoculated with RNA transcripts from clone pSHEV-1, which contained three nonsilent mutations in the ORF2 capsid gene, had a delayed appearance of seroconversion and fecal virus shedding and had undetectable viremia. The availability of these infectious cDNA clones affords us an opportunity to understand the mechanisms of cross-species infection by constructing chimeric human and swine HEVs. JF - Journal of Virology AU - Huang, Y W AU - Haqshenas, G AU - Kasorndorkbua, C AU - Halbur, P G AU - Emerson, SU AU - Meng, X J AD - Center for Molecular Medicine and Infectious Diseases, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia. College of Veterinary Medicine, Iowa State University, Ames, Iowa. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Y1 - 2005/02/01/ PY - 2005 DA - 2005 Feb 01 SP - 1552 EP - 1558 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 79 IS - 3 SN - 0022-538X, 0022-538X KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts; Virology & AIDS Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Hepatocytes KW - Seroconversion KW - Site-directed mutagenesis KW - Capsids KW - Replication KW - Transcription KW - Nucleotides KW - RNA KW - Inoculation KW - Viremia KW - Mutation KW - Genomes KW - Infection KW - Conserved sequence KW - Hepatitis E virus KW - Transfection KW - cDNA KW - N 14025:RNA/DNA role in infection & immune response KW - W2 32070:Animals KW - V 22150:Animal models & experimentally-induced viral infections KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17772309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Capped+RNA+Transcripts+of+Full-Length+cDNA+Clones+of+Swine+Hepatitis+E+Virus+Are+Replication+Competent+When+Transfected+into+Huh7+Cells+and+Infectious+When+Intrahepatically+Inoculated+into+Pigs&rft.au=Huang%2C+Y+W%3BHaqshenas%2C+G%3BKasorndorkbua%2C+C%3BHalbur%2C+P+G%3BEmerson%2C+SU%3BMeng%2C+X+J&rft.aulast=Huang&rft.aufirst=Y&rft.date=2005-02-01&rft.volume=79&rft.issue=3&rft.spage=1552&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hepatitis E virus; cDNA; RNA; Replication; Transfection; Viremia; Capsids; Inoculation; Infection; Seroconversion; Mutation; Nucleotides; Transcription; Genomes; Hepatocytes; Site-directed mutagenesis; Conserved sequence ER - TY - JOUR T1 - CYP1A1 and CYP1B1 genotypes, haplotypes, and TCDD-induced gene expression in subjects from Seveso, Italy AN - 17765849; 6133375 AB - 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) is highly toxic in experimental animals, and is known to induce cytochrome P450 (CYP) gene expression. We investigated the effect of CYP1A1 and CYP1B1 variant genotypes and haplotypes on CYP1A1 and CYP1B1 mRNA expression and ethoxyresorufin-O-deethylase (EROD) activity in lymphocytes from 121 subjects from the Seveso population, Italy, accidentally exposed to TCDD in 1976. The 3'UTR 3801T>C and I462V variants of CYP1A1 were present in 16% and 6% of the subjects, respectively. The frequency of CYP1B1 variants was 85.2% for L432V, 49.6% for R48G and A119S, and 28.7% for N453S. There was complete linkage disequilibrium (LD) among the CYP1B1 variant loci (D' =-1) and high LD among the CYP1A1 loci (D' = 0.86). Gene expression measured by RT-PCR did not vary by CYP1B1 genotype in uncultured lymphocytes. However, when lymphocytes were treated in vitro with 10 nM TCDD, CYP1B1 and CYP1A1 mRNA expression was strongly induced and modified by CYP variant alleles. Specifically, the CYP1B13 haplotype (L432V) was associated with increased CYP1B1 mRNA expression (P = 0.03), following an additive model; the CYP1A1 I462V polymorphism was positively, although not significantly, associated with CYP1A1 expression. The CYP1B13 variant may have affected CYP1B1 expression in subjects highly and acutely exposed to dioxin at the time of the accident. Although based on small number of subjects, a slight increase in eczema (P = 0.05, n = 8) and urticaria (P = 0.02, n = 2) was observed 20 years after the accident in subjects carrying the CYP1B13 allele. Genetic variation in cytochrome P450 induction may identify subjects with variable responsiveness to TCDD and potentially increased risk of disease. JF - Toxicology AU - Landi, M T AU - Bergen, A W AU - Baccarelli, A AU - Patterson, D G AU - Grassman, J AU - Ter-Minassian, M AU - Mocarelli, P AU - Caporaso, N AU - Masten, SA AU - Pesatori, A C AU - Pittman, G S AU - Bell, DA AD - Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Blvd. EPS, Bethesda, MD 20892- 7236, USA, landim@mail.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 191 EP - 202 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 207 IS - 2 SN - 0300-483X, 0300-483X KW - Toxicology Abstracts KW - 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin KW - CYP1A1 KW - CYP1B1 KW - Genotypes KW - Haplotypes KW - Gene expression KW - EROD, ethoxyresorufin-O-deethylase KW - TCDD, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin KW - CYP, cytochrome P450 KW - LD, linkage disequilibrium KW - AhR, aryl hydrocarbon receptor KW - SNP, single nucleotide polymorphisms KW - ppt, parts per trillion KW - RT-PCR, reverse transcription polymerase chain reaction KW - CI, confidence interval KW - IQR, inter-quartile range KW - EM-algorithm, expectation-maximization algorithm KW - SAM, single-point additive model KW - 3' Untranslated regions KW - Gene polymorphism KW - Animal models KW - Genetic diversity KW - TCDD KW - Urticaria KW - Lymphocytes KW - Eczema KW - Models KW - Linkage disequilibrium KW - Accidents KW - CYP1A1 protein KW - Polymerase chain reaction KW - Cytochrome P450 KW - CYP gene KW - Dioxin KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17765849?accountid=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=CYP1A1+and+CYP1B1+genotypes%2C+haplotypes%2C+and+TCDD-induced+gene+expression+in+subjects+from+Seveso%2C+Italy&rft.au=Landi%2C+M+T%3BBergen%2C+A+W%3BBaccarelli%2C+A%3BPatterson%2C+D+G%3BGrassman%2C+J%3BTer-Minassian%2C+M%3BMocarelli%2C+P%3BCaporaso%2C+N%3BMasten%2C+SA%3BPesatori%2C+A+C%3BPittman%2C+G+S%3BBell%2C+DA&rft.aulast=Landi&rft.aufirst=M&rft.date=2005-02-01&rft.volume=207&rft.issue=2&rft.spage=191&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2Fj.tox.2004.08.021 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - 3' Untranslated regions; Gene polymorphism; Animal models; TCDD; Genetic diversity; Urticaria; Eczema; Genotypes; Lymphocytes; Models; Gene expression; Linkage disequilibrium; Accidents; CYP1A1 protein; Haplotypes; Polymerase chain reaction; Cytochrome P450; Dioxin; CYP gene DO - http://dx.doi.org/10.1016/j.tox.2004.08.021 ER - TY - JOUR T1 - Central amygdala ERK signaling pathway is critical to incubation of cocaine craving AN - 17610131; 6156439 AB - Using a rat model of craving and relapse, we have previously found time-dependent increases in cue-induced cocaine seeking over the first months of withdrawal from cocaine, suggesting that drug craving incubates over time. Here, we explored the role of the amygdala extracellular signal-regulated kinase (ERK) signaling pathway in this incubation. Cocaine seeking induced by exposure to cocaine cues was substantially higher after 30 withdrawal days than after 1 withdrawal day. Exposure to these cues increased ERK phosphorylation in the central, but not the basolateral, amygdala after 30 d, but not 1 d, of withdrawal. After 30 d of withdrawal from cocaine, inhibition of central, but not basolateral, amygdala ERK phosphorylation decreased cocaine seeking. After 1 d of withdrawal, stimulation of central amygdala ERK phosphorylation increased cocaine seeking. Results suggest that the incubation of cocaine craving is mediated by time-dependent increases in the responsiveness of the central amygdala ERK pathway to cocaine cues. JF - Nature Neuroscience AU - Lu, Lin AU - Hope, Bruce T AU - Dempsey, Jack AU - Liu, Shirley Y AU - Bossert, Jennifer M AU - Shaham, Yavin AD - Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA, yshaham@intra.nida.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 212 EP - 219 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 8 IS - 2 SN - 1097-6256, 1097-6256 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/17610131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Neuroscience&rft.atitle=Central+amygdala+ERK+signaling+pathway+is+critical+to+incubation+of+cocaine+craving&rft.au=Lu%2C+Lin%3BHope%2C+Bruce+T%3BDempsey%2C+Jack%3BLiu%2C+Shirley+Y%3BBossert%2C+Jennifer+M%3BShaham%2C+Yavin&rft.aulast=Lu&rft.aufirst=Lin&rft.date=2005-02-01&rft.volume=8&rft.issue=2&rft.spage=212&rft.isbn=&rft.btitle=&rft.title=Nature+Neuroscience&rft.issn=10976256&rft_id=info:doi/10.1038%2Fnn1383 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-04-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1038/nn1383 ER - TY - JOUR T1 - Hepatocellular Carcinoma and Polymorphisms in Carcinogen-Metabolizing and DNA Repair Enzymes in a Population with Aflatoxin Exposure and Hepatitis B Virus Endemicity AN - 17558665; 6167153 AB - High rates of hepatocellular carcinoma (HCC) in The Gambia, West Africa, are primarily due to a high prevalence of chronic hepatitis B virus infection and heavy aflatoxin exposure via groundnut consumption. We investigated genetic polymorphisms in carcinogen-metabolizing (GSTM1, GSTT1, HYL1*2) and DNA repair (XRCC1) enzymes in a hospital-based case-control study. Incident HCC cases (n = 216) were compared with frequency-matched controls (n = 408) with no clinically apparent liver disease. Although the prevalence of variant genotypes was generally low, in multivariable analysis (adjusting for demographic factors, hepatitis B virus, hepatitis C virus, and TP53 status), the GSTM1-null genotype [odds ratio (OR), 2.45; 95% confidence interval (95% CI), 1.21-4.95] and the heterozygote XRCC1-399 AG genotype (OR, 3.18; 95% CI, 1.35-7.51) were significantly associated with HCC. A weak association of the HYL1*2 polymorphism with HCC was observed but did not reach statistical significance. GSTT1 was not associated with HCC. The risk for HCC with null GSTM1 was most prominent among those with the highest groundnut consumption (OR, 4.67; 95% CI, 1.45-15.1) and was not evident among those with less than the mean groundnut intake (OR, 0.64; 95% CI, 0.20-2.02). Among participants who had all three suspected aflatoxin- related high-risk genotypes [GSTM1 null, HLY1*2 (HY/HH), and XRCC1 (AG/GG)], a significant 15-fold increased risk of HCC was observed albeit with imprecise estimates (OR, 14.7; 95% CI, 1.27-169). Our findings suggest that genetic modulation of carcinogen metabolism and DNA repair can alter susceptibility to HCC and that these effects may be modified by environmental factors. JF - Cancer Epidemiology, Biomarkers & Prevention AU - Kirk, Gregory D AU - Turner, Paul C AU - Gong, Yunyun AU - Lesi, Olufunmilayo A AU - Mendy, Maimuna AU - Goedert, James J AU - Hall, Andrew J AU - Whittle, Hilton AU - Hainaut, Pierre AU - Montesano, Ruggero AU - Wild, Christopher P AD - Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH/Department of Health and Human Services, Bethesda, Maryland Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 373 EP - 379 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 14 IS - 2 SN - 1055-9965, 1055-9965 KW - Biochemistry Abstracts 2: Nucleic Acids; Virology & AIDS Abstracts; Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - Statistics KW - Carcinogens KW - Liver diseases KW - Aflatoxins KW - p53 protein KW - Epidemiology KW - Hepatitis C virus KW - Heterozygotes KW - Chronic infection KW - Metabolism KW - Gene polymorphism KW - XRCC1 protein KW - Environmental factors KW - Demography KW - Risk factors KW - Hepatocellular carcinoma KW - Hepatitis B virus KW - DNA repair KW - biomarkers KW - B 26248:DNA repair KW - N 14025:RNA/DNA role in infection & immune response KW - X 24171:Microbial KW - V 22114:Human oncogenic viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17558665?accountid=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+Epidemiology%2C+Biomarkers+%26+Prevention&rft.atitle=Hepatocellular+Carcinoma+and+Polymorphisms+in+Carcinogen-Metabolizing+and+DNA+Repair+Enzymes+in+a+Population+with+Aflatoxin+Exposure+and+Hepatitis+B+Virus+Endemicity&rft.au=Kirk%2C+Gregory+D%3BTurner%2C+Paul+C%3BGong%2C+Yunyun%3BLesi%2C+Olufunmilayo+A%3BMendy%2C+Maimuna%3BGoedert%2C+James+J%3BHall%2C+Andrew+J%3BWhittle%2C+Hilton%3BHainaut%2C+Pierre%3BMontesano%2C+Ruggero%3BWild%2C+Christopher+P&rft.aulast=Kirk&rft.aufirst=Gregory&rft.date=2005-02-01&rft.volume=14&rft.issue=2&rft.spage=373&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hepatitis B virus; Hepatitis C virus; Gene polymorphism; DNA repair; Aflatoxins; XRCC1 protein; Hepatocellular carcinoma; Liver diseases; biomarkers; p53 protein; Chronic infection; Demography; Epidemiology; Environmental factors; Carcinogens; Statistics; Heterozygotes; Metabolism; Risk factors ER - TY - JOUR T1 - Fatal intra-brain heat accumulation induced by meth-amphetamine at normothermic conditions in rats AN - 17386139; 6499504 AB - Objectives: While meth-amphetamine (METH) is known to induce brain hyperthermia, the role of environment and heat dissipation in modulating this hyperthermia needs to be clarified. Methodology: The effects of METH (9 mg/kg, sc) on brain (nucleus accumbens and hippocampus) and muscle (musculus temporalis) temperatures were tested in rats under quiet resting conditions at standard (23 degree C) and warm (29 degree C, normothermic conditions) environmental temperatures. Results: While at 23 degree C METH induced robust hyperthermia (>3.5 degree C) with more rapid and stronger changes in both brain structures than in the muscle without lethality, at 29 degree C METH pushed brain temperature to its biological limits (>41 degree C), resulting in fatalities in five of six tested animals. Conclusion: METH use under conditions of diminished heat dissipation results in stronger intra-brain heat accumulation and is more hazardous than under standard laboratory conditions. JF - International Journal of Neuroprotection and Neuroregeneration AU - Brown, P L AU - Kiyatkin, E A AD - Cellular Neurobiology Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, DHHS, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA, ekiyatki@intra.nida.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 86 EP - 90 VL - 1 IS - 2 SN - 1745-1183, 1745-1183 KW - rats KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Temperature effects KW - Nucleus accumbens KW - Hyperthermia KW - Methamphetamine KW - Lethality KW - Heat KW - Hippocampus KW - Brain KW - Muscles KW - Neuroprotection 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/17386139?accountid=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+Neuroprotection+and+Neuroregeneration&rft.atitle=Fatal+intra-brain+heat+accumulation+induced+by+meth-amphetamine+at+normothermic+conditions+in+rats&rft.au=Brown%2C+P+L%3BKiyatkin%2C+E+A&rft.aulast=Brown&rft.aufirst=P&rft.date=2005-02-01&rft.volume=1&rft.issue=2&rft.spage=86&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Neuroprotection+and+Neuroregeneration&rft.issn=17451183&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Temperature effects; Nucleus accumbens; Methamphetamine; Hyperthermia; Lethality; Hippocampus; Heat; Muscles; Brain; Neuroprotection ER - TY - JOUR T1 - Study of Ocular Transport of Drugs Released from an Intravitreal Implant Using Magnetic Resonance Imaging AN - 17351231; 6401233 AB - Ensuring optimum delivery of therapeutic agents in the eye requires detailed information about the transport mechanisms and elimination pathways available. This knowledge can guide the development of new drug delivery devices. In this study, we investigated the movement of a drug surrogate, Gd-DTPA (Magnevist registered ) released from a polymer-based implant in rabbit vitreous using T sub(1)-weighted magnetic resonance imaging (MRI). Intensity values in the MRI data were converted to concentration by comparison with calibration samples. Concentration profiles approaching pseudosteady state showed gradients from the implant toward the retinal surface, suggesting that diffusion was occurring into the retinal-choroidal-scleral (RCS) membrane. Gd-DTPA concentration varied from high values near the implant to lower values distal to the implant. Such regional concentration differences throughout the vitreous may have clinical significance when attempting to treat ubiquitous eye diseases using a single positional implant. We developed a finite element mathematical model of the rabbit eye and compared the MRI experimental concentration data with simulation concentration profiles. The model utilized a diffusion coefficient of Gd-DTPA in the vitreous of 2.8 x 10 super(-6), cm super(2), s super(-1) and yielded a diffusion coefficient for Gd-DTPA through the simulated composite posterior membrane (representing the retina-choroid-sclera membrane) of 6.0 x 10 super(-8), cm super(2), s super(-1). Since the model membrane was 0.03-cm thick, this resulted in an effective membrane permeability of 2.0 x 10 super(-6), cm, s super(-1). Convective movement of Gd-DTPA was shown to have minimal effect on the concentration profiles since the Peclet number was 0.09 for this system. JF - Annals of Biomedical Engineering AU - Kim, Hyuncheol AU - Lizak, Martin J AU - Tansey, Ginger AU - Csaky, Karl G AU - Robinson, Michael R AU - Yuan, Peng AU - Wang, Nam Sun AU - Lutz, Robert J AD - Drug Delivery and Kinetics Resource, Building 13, Room 3N17, 9000 Rockville Pike, Bethesda, MD, 20892, rjlutz@mail.nih.gov Y1 - 2005/02// PY - 2005 DA - Feb 2005 SP - 150 EP - 164 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 33 IS - 2 SN - 0090-6964, 0090-6964 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts 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/17351231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Study+of+Ocular+Transport+of+Drugs+Released+from+an+Intravitreal+Implant+Using+Magnetic+Resonance+Imaging&rft.au=Kim%2C+Hyuncheol%3BLizak%2C+Martin+J%3BTansey%2C+Ginger%3BCsaky%2C+Karl+G%3BRobinson%2C+Michael+R%3BYuan%2C+Peng%3BWang%2C+Nam+Sun%3BLutz%2C+Robert+J&rft.aulast=Kim&rft.aufirst=Hyuncheol&rft.date=2005-02-01&rft.volume=33&rft.issue=2&rft.spage=150&rft.isbn=&rft.btitle=&rft.title=Annals+of+Biomedical+Engineering&rft.issn=00906964&rft_id=info:doi/10.1007%2Fs10439-005-8974-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1007/s10439-005-8974-7 ER - TY - JOUR T1 - Inhibition of VEGF receptors significantly impairs mammary cancer growth in C3(1)/Tag transgenic mice through antiangiogenic and non-antiangiogenic mechanisms. AN - 67387226; 15592523 AB - Cancer growth and progression is often critically influenced by the production of vascular endothelial growth factor (VEGF), a key mediator of angiogenesis. VEGF produced by tumor cells stimulates endothelial cell growth through the binding and activation of the KDR/Flk-1 receptor (VEGFR-2) on endothelial cells. Recently, some human breast cancer epithelial cells have been shown to express VEGF receptors, suggesting a potential autocrine-mediated growth stimulation of a subset of cancers by VEGF. We demonstrate that mammary tumors in the C3(1)/Tag transgenic model express VEGF and VEGF receptors and tumor growth is stimulated by this autocrine mechanism. GW654652, an indazolylpyrimidine, is a VEGFRs tyrosine kinase inhibitor that dramatically reduces both angiogenesis and tumor cell growth in this model, as demonstrated using both in vitro and in vivo assays. GW654652 significantly decreased cell proliferation and induced apoptosis in human umbilical vein endothelial cells and M6 mammary tumor cells derived from C3(1)/Tag (Tag: simian virus 40 T-antigen) transgenic mice. A 75% reduction in VEGF-induced angiogenesis was observed with GW654652 using the chick chorioallantoic membrane assay, whereas GW654652 produced an approximately 85% reduction in angiogenesis as assessed by the Matrigel plug assay. A profound inhibitory effect on tumor growth in the C3(1)/Tag transgenic model of human breast cancer was observed with oral administration of GW654652 as measured by delayed tumor onset, decreased multiplicity, reduced tumor volume, and extended animal survival. The antitumor effects of GW654652 were associated with reduced tumor vascularization and no apparent toxicity. Tumor growth, however, rapidly advanced following cessation of treatment. This is the first demonstration that a VEGF receptor inhibitor, GW654652, has a strong inhibitory effect on angiogenesis and tumor progression in a transgenic model of mammary cancer, suggesting that this is a useful approach for preclinical testing of such agents. JF - Oncogene AU - Huh, Jung-Im AU - Calvo, Alfonso AU - Stafford, Jeffrey AU - Cheung, Mui AU - Kumar, Rakesh AU - Philp, Deborah AU - Kleinman, Hynda K AU - Green, Jeffrey E AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2005/01/27/ PY - 2005 DA - 2005 Jan 27 SP - 790 EP - 800 VL - 24 IS - 5 SN - 0950-9232, 0950-9232 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Antineoplastic Agents KW - DNA Primers KW - GW 654652 KW - Imidazoles KW - Pyrimidines KW - RNA, Small Interfering KW - Receptors, Vascular Endothelial Growth Factor KW - EC 2.7.10.1 KW - Vascular Endothelial Growth Factor Receptor-1 KW - Vascular Endothelial Growth Factor Receptor-2 KW - Index Medicus KW - Animals KW - Apoptosis KW - Imidazoles -- pharmacology KW - Humans KW - Mice, Transgenic KW - Flow Cytometry KW - Vascular Endothelial Growth Factor Receptor-2 -- antagonists & inhibitors KW - Chorion -- cytology KW - Vascular Endothelial Growth Factor Receptor-1 -- antagonists & inhibitors KW - Vascular Endothelial Growth Factor Receptor-1 -- genetics KW - Endothelium, Vascular -- cytology KW - Vascular Endothelial Growth Factor Receptor-2 -- genetics KW - Allantois -- cytology KW - Cell Division -- drug effects KW - Pyrimidines -- pharmacology KW - Mice KW - RNA, Small Interfering -- genetics KW - Antigens, Polyomavirus Transforming -- genetics KW - Neovascularization, Physiologic -- drug effects KW - Reverse Transcriptase Polymerase Chain Reaction KW - Neovascularization, Pathologic -- pathology KW - Transfection KW - Antineoplastic Agents -- toxicity KW - Umbilical Veins KW - Female KW - Receptors, Vascular Endothelial Growth Factor -- antagonists & inhibitors KW - Mammary Neoplasms, Animal -- pathology KW - Receptors, Vascular Endothelial Growth Factor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67387226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+VEGF+receptors+significantly+impairs+mammary+cancer+growth+in+C3%281%29%2FTag+transgenic+mice+through+antiangiogenic+and+non-antiangiogenic+mechanisms.&rft.au=Huh%2C+Jung-Im%3BCalvo%2C+Alfonso%3BStafford%2C+Jeffrey%3BCheung%2C+Mui%3BKumar%2C+Rakesh%3BPhilp%2C+Deborah%3BKleinman%2C+Hynda+K%3BGreen%2C+Jeffrey+E&rft.aulast=Huh&rft.aufirst=Jung-Im&rft.date=2005-01-27&rft.volume=24&rft.issue=5&rft.spage=790&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-07 N1 - Date created - 2005-01-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Oncogene. 2005 Jun 9;24(25):4164 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The PI3K-mediated activation of CRAC independently regulates adenylyl cyclase activation and chemotaxis. AN - 67377851; 15668169 AB - The ability of a cell to detect an external chemical signal and initiate a program of directed migration along a gradient comprises the fundamental process called chemotaxis. Investigations in Dictyostelium discoideum and neutrophils have established that pleckstrin homology (PH) domain-containing proteins that bind to the PI3K products PI(3,4)P2 and PI(3,4,5)P3, such as CRAC (cytosolic regulator of adenylyl cyclase) and Akt/PKB, translocate specifically to the leading edge of chemotaxing cells. CRAC is essential for the chemoattractant-mediated activation of the adenylyl cyclase ACA, which converts ATP into cAMP, the primary chemoattractant for D. discoideum. The mechanisms by which CRAC activates ACA remain to be determined. We now show that in addition to its essential role in the activation of ACA, CRAC is involved in regulating chemotaxis. Through mutagenesis, we show that these two functions are independently regulated downstream of PI3K. A CRAC mutant that has lost the capacity to bind PI3K products does not support chemotaxis and shows minimal ACA activation. Finally, overexpression of CRAC and various CRAC mutants show strong effects on ACA activation with little effect on chemotaxis. These findings establish that chemoattractant-mediated activation of PI3K is important for the CRAC-dependent regulation of both chemotaxis and adenylyl cyclase activation. JF - Current biology : CB AU - Comer, Frank I AU - Lippincott, Christopher K AU - Masbad, Joseph J AU - Parent, Carole A AD - Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2005/01/26/ PY - 2005 DA - 2005 Jan 26 SP - 134 EP - 139 VL - 15 IS - 2 SN - 0960-9822, 0960-9822 KW - Protozoan Proteins KW - 0 KW - dagA protein, Dictyostelium KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Index Medicus KW - Animals KW - Blotting, Western KW - Plasmids -- genetics KW - Cells, Cultured KW - Transformation, Genetic KW - Gene Expression KW - Enzyme Activation -- physiology KW - Dictyostelium KW - Mutagenesis KW - Protozoan Proteins -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Chemotaxis -- physiology KW - Adenylyl Cyclases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67377851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+PI3K-mediated+activation+of+CRAC+independently+regulates+adenylyl+cyclase+activation+and+chemotaxis.&rft.au=Comer%2C+Frank+I%3BLippincott%2C+Christopher+K%3BMasbad%2C+Joseph+J%3BParent%2C+Carole+A&rft.aulast=Comer&rft.aufirst=Frank&rft.date=2005-01-26&rft.volume=15&rft.issue=2&rft.spage=134&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 - 2005-04-15 N1 - Date created - 2005-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fully automated micro- and nanoscale one- or two-dimensional high-performance liquid chromatography system for liquid chromatography-mass spectrometry compatible with non-volatile salts for ion exchange chromatography. AN - 67420201; 15700457 AB - A one- or two-dimensional high performance liquid chromatography system for electrospray ionization mass spectrometers has been developed that is optimized for ion exchange and reversed phase separations. A unique and simple valve configuration permits the use of a variety of non-volatile salts; ammonium sulfate was used in an example of strong cation exchange separations. The system was designed and evaluated for both micro- and nanoflow chromatography. The peptide detection limit was approximately 100 fmol for micro- and 20 fmol for nanoflow, demonstrating the concentration and mass sensitivity improvements expected with nanoelectrospray ionization. The 1D/2D-HPLC MS system is fully automated for routine peptide analyses, compatible with direct injection of proteolytic digests, and exhibits chromatographic reproducibility and sensitivity. Software permits operator selection of either a 1D or 2D configuration with corresponding system parameters as required for individual samples. The hardware elements and resulting performance are described in this paper. JF - Journal of chromatography. A AU - Masuda, Junichi AU - Maynard, Dawn M AU - Nishimura, Masayuki AU - Ueda, Teruhisa AU - Kowalak, Jeffrey A AU - Markey, Sanford P AD - Laboratory of Neurotoxicology, National Institute of Mental Health, National Institute of Health, Bethesda, MD 20892-1262, USA. Y1 - 2005/01/21/ PY - 2005 DA - 2005 Jan 21 SP - 57 EP - 69 VL - 1063 IS - 1-2 SN - 0021-9673, 0021-9673 KW - Peptides KW - 0 KW - Salts KW - Index Medicus KW - Sensitivity and Specificity KW - Reproducibility of Results KW - Peptides -- analysis KW - Automation KW - Nanotechnology KW - Chromatography, Ion Exchange -- methods KW - Chromatography, High Pressure Liquid -- methods KW - Salts -- chemistry KW - Spectrometry, Mass, Electrospray Ionization -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67420201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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.+A&rft.atitle=Fully+automated+micro-+and+nanoscale+one-+or+two-dimensional+high-performance+liquid+chromatography+system+for+liquid+chromatography-mass+spectrometry+compatible+with+non-volatile+salts+for+ion+exchange+chromatography.&rft.au=Masuda%2C+Junichi%3BMaynard%2C+Dawn+M%3BNishimura%2C+Masayuki%3BUeda%2C+Teruhisa%3BKowalak%2C+Jeffrey+A%3BMarkey%2C+Sanford+P&rft.aulast=Masuda&rft.aufirst=Junichi&rft.date=2005-01-21&rft.volume=1063&rft.issue=1-2&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Journal+of+chromatography.+A&rft.issn=00219673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-18 N1 - Date created - 2005-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Macropinocytosis is the endocytic pathway that mediates macrophage foam cell formation with native low density lipoprotein. AN - 67378580; 15533943 AB - Previously, we reported that fluid-phase endocytosis of native LDL by PMA-activated human monocytederived macrophages converted these macrophages into cholesterol-enriched foam cells (Kruth, H. S., Huang, W., Ishii, I., and Zhang, W. Y. (2002) J. Biol. Chem. 277, 34573-34580). Uptake of fluid by cells can occur either by micropinocytosis within vesicles (40-fold over its concentration in the culture medium consistent with macropinosome shrinkage by maturation into multivesicular body endosomes. Macropinocytosis of LDL taken up in the fluid phase without receptor-mediated binding of LDL is a novel endocytic pathway that generates macrophage foam cells. Macropinocytosis in macrophages and possibly other vascular cells is a new pathway to target for modulating foam cell formation in atherosclerosis. JF - The Journal of biological chemistry AU - Kruth, Howard S AU - Jones, Nancy L AU - Huang, Wei AU - Zhao, Bin AU - Ishii, Itsuko AU - Chang, Janet AU - Combs, Christian A AU - Malide, Daniela AU - Zhang, Wei-Yang AD - Section of Experimental Atherosclerosis, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1422, USA. kruthh@nhlbi.nih.gov Y1 - 2005/01/21/ PY - 2005 DA - 2005 Jan 21 SP - 2352 EP - 2360 VL - 280 IS - 3 SN - 0021-9258, 0021-9258 KW - Chromones KW - 0 KW - Enzyme Inhibitors KW - Lipoproteins, LDL KW - Morpholines KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Proton-Translocating ATPases KW - EC 3.6.3.14 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Humans KW - Morpholines -- pharmacology KW - Macrophage Activation -- drug effects KW - Proton-Translocating ATPases -- metabolism KW - Chromones -- pharmacology KW - Cells, Cultured KW - Enzyme Inhibitors -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Lipoproteins, LDL -- metabolism KW - Microscopy, Electron KW - Vacuoles -- enzymology KW - Immunohistochemistry KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Endocytosis KW - Foam Cells -- metabolism KW - Pinocytosis KW - Foam Cells -- ultrastructure KW - Foam Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67378580?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Macropinocytosis+is+the+endocytic+pathway+that+mediates+macrophage+foam+cell+formation+with+native+low+density+lipoprotein.&rft.au=Kruth%2C+Howard+S%3BJones%2C+Nancy+L%3BHuang%2C+Wei%3BZhao%2C+Bin%3BIshii%2C+Itsuko%3BChang%2C+Janet%3BCombs%2C+Christian+A%3BMalide%2C+Daniela%3BZhang%2C+Wei-Yang&rft.aulast=Kruth&rft.aufirst=Howard&rft.date=2005-01-21&rft.volume=280&rft.issue=3&rft.spage=2352&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 - 2005-04-13 N1 - Date created - 2005-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of Raf-1 by direct feedback phosphorylation. AN - 67369723; 15664191 AB - The Raf-1 kinase is an important signaling molecule, functioning in the Ras pathway to transmit mitogenic, differentiative, and oncogenic signals to the downstream kinases MEK and ERK. Because of its integral role in cell signaling, Raf-1 activity must be precisely controlled. Previous studies have shown that phosphorylation is required for Raf-1 activation, and here, we identify six phosphorylation sites that contribute to the downregulation of Raf-1 after mitogen stimulation. Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli. The hyperphosphorylated/desensitized Raf-1 is subsequently dephosphorylated and returned to a signaling-competent state through interactions with the protein phosphatase PP2A and the prolyl isomerase Pin1. These findings elucidate a critical Raf-1 regulatory mechanism that contributes to the sensitive, temporal modulation of Ras signaling. JF - Molecular cell AU - Dougherty, Michele K AU - Müller, Jürgen AU - Ritt, Daniel A AU - Zhou, Ming AU - Zhou, Xiao Zhen AU - Copeland, Terry D AU - Conrads, Thomas P AU - Veenstra, Timothy D AU - Lu, Kun Ping AU - Morrison, Deborah K AD - Laboratory of Protein Dynamics and Signaling, National Cancer Institute-Frederick, Frederick, MD 21702, USA. Y1 - 2005/01/21/ PY - 2005 DA - 2005 Jan 21 SP - 215 EP - 224 VL - 17 IS - 2 SN - 1097-2765, 1097-2765 KW - Isoenzymes KW - 0 KW - NIMA-Interacting Peptidylprolyl Isomerase KW - Peptides KW - Platelet-Derived Growth Factor KW - Receptors, Platelet-Derived Growth Factor KW - EC 2.7.10.1 KW - Proto-Oncogene Proteins c-raf KW - EC 2.7.11.1 KW - Extracellular Signal-Regulated MAP Kinases KW - EC 2.7.11.24 KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - ras Proteins KW - EC 3.6.5.2 KW - Peptidylprolyl Isomerase KW - EC 5.2.1.8 KW - Pin1 protein, mouse KW - Index Medicus KW - Receptors, Platelet-Derived Growth Factor -- metabolism KW - Platelet-Derived Growth Factor -- metabolism KW - Animals KW - Enzyme Activation KW - Peptides -- metabolism KW - Mice KW - Extracellular Signal-Regulated MAP Kinases -- metabolism KW - Isoenzymes -- metabolism KW - Mutagenesis, Site-Directed KW - Xenopus laevis KW - Phosphorylation KW - Phosphoprotein Phosphatases -- metabolism KW - ras Proteins -- metabolism KW - Peptides -- genetics KW - Cell Line KW - Peptidylprolyl Isomerase -- metabolism KW - Down-Regulation KW - Proto-Oncogene Proteins c-raf -- genetics KW - Proto-Oncogene Proteins c-raf -- metabolism KW - Feedback, Physiological KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67369723?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Regulation+of+Raf-1+by+direct+feedback+phosphorylation.&rft.au=Dougherty%2C+Michele+K%3BM%C3%BCller%2C+J%C3%BCrgen%3BRitt%2C+Daniel+A%3BZhou%2C+Ming%3BZhou%2C+Xiao+Zhen%3BCopeland%2C+Terry+D%3BConrads%2C+Thomas+P%3BVeenstra%2C+Timothy+D%3BLu%2C+Kun+Ping%3BMorrison%2C+Deborah+K&rft.aulast=Dougherty&rft.aufirst=Michele&rft.date=2005-01-21&rft.volume=17&rft.issue=2&rft.spage=215&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 - 2005-03-18 N1 - Date created - 2005-01-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Mol Cell. 2005 Jan 21;17(2):164-6 [15664184] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Blebbistatin, a myosin II inhibitor, is photoinactivated by blue light. AN - 67365900; 15641783 AB - Blebbistatin is a small molecule inhibitor discovered in a screen for inhibitors of nonmuscle myosin IIA. Blebbistatin inhibits the actin-activated MgATPase activity and in vitro motility of class II myosins. In cells, it has been shown to inhibit contraction of the cytokinetic ring. Blebbistatin has some photochemical properties that may affect its behavior in cells. In particular, we have found that exposure to light at wavelengths below 488 nm rapidly inactivates the inhibitory action of blebbistatin using the in vitro motility of myosin as an assay. In addition, the inhibition of cytokinetic ring contraction can be reversed by exposure of the cells to blue light. This property may be useful in locally reversing the action of blebbistatin treatment in a cell. However, caution should be exercised as free radicals may be produced upon irradiation of blebbistatin that could result in cell damage. JF - Biochemistry AU - Sakamoto, Takeshi AU - Limouze, John AU - Combs, Christian A AU - Straight, Aaron F AU - Sellers, James R AD - Laboratory of Molecular Cardiology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1762, USA. Y1 - 2005/01/18/ PY - 2005 DA - 2005 Jan 18 SP - 584 EP - 588 VL - 44 IS - 2 SN - 0006-2960, 0006-2960 KW - Actins KW - 0 KW - Free Radicals KW - Heterocyclic Compounds, 4 or More Rings KW - blebbistatin KW - 20WC4J7CQ6 KW - Nonmuscle Myosin Type IIA KW - EC 3.6.1.- KW - Index Medicus KW - Photochemistry KW - Free Radicals -- toxicity KW - Microscopy, Confocal KW - Actins -- physiology KW - Animals KW - Videotape Recording KW - HeLa Cells KW - Muscle, Skeletal -- physiology KW - Humans KW - Mitosis -- radiation effects KW - Rabbits KW - Dose-Response Relationship, Radiation KW - Muscle Contraction -- physiology KW - Muscle, Skeletal -- drug effects KW - Free Radicals -- metabolism KW - Microscopy, Fluorescence KW - Actins -- antagonists & inhibitors KW - Muscle Contraction -- drug effects KW - Mitosis -- drug effects KW - Nonmuscle Myosin Type IIA -- antagonists & inhibitors KW - Heterocyclic Compounds, 4 or More Rings -- metabolism KW - Heterocyclic Compounds, 4 or More Rings -- antagonists & inhibitors KW - Heterocyclic Compounds, 4 or More Rings -- pharmacology KW - Light KW - Nonmuscle Myosin Type IIA -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67365900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Blebbistatin%2C+a+myosin+II+inhibitor%2C+is+photoinactivated+by+blue+light.&rft.au=Sakamoto%2C+Takeshi%3BLimouze%2C+John%3BCombs%2C+Christian+A%3BStraight%2C+Aaron+F%3BSellers%2C+James+R&rft.aulast=Sakamoto&rft.aufirst=Takeshi&rft.date=2005-01-18&rft.volume=44&rft.issue=2&rft.spage=584&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-28 N1 - Date created - 2005-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis AN - 17621577; 6175527 AB - Methamphetamine [METH ("speed")] is an abused psychostimulant that can cause psychotic, cognitive, and psychomotor impairment in humans. These signs and symptoms are thought to be related to dysfunctions in basal ganglionic structures of the brain. To identify possible molecular bases for these clinical manifestations, we first used cDNA microarray technology to measure METH-induced transcriptional responses in the striatum of rats treated with an apoptosis-inducing dose of the drug. METH injection resulted in increased expression of members of the Jun, Egr, and Nur77 subfamilies of transcription factors (TFs), changes that were confirmed by quantitative PCR. Because pathways linked to these factors are involved in the up-regulation of Fas ligand (FasL), FasL mRNA was quantified and found to be increased. Immunohistochemical studies also revealed METH-induced increased FasL protein expression in striatal GABAergic neurons that express enkephalin. Moreover, there were METH-mediated increases in calcineurin, as well as shuttling of nuclear factor of activated T cells (NFAT)c3 and NFATc4 from the cytosol to the nucleus of METH-treated rats, mechanisms also known to be involved in FasL regulation. Furthermore, METH induced cleavage of caspase-3 in FasL-and Fas-containing neurons. Finally, the METH-induced changes in the FasL-Fas death pathway were attenuated by pretreatment with the dopamine D1 receptor antagonist, SCH23390 which also caused attenuation of METH-induced apoptosis. These observations indicate that METH causes some of its neurodegenerative effects, in part, via stimulation of the Fas-mediated cell death pathway consequent to FasL up-regulation mediated by activation of multiple TFs. JF - Proceedings of the National Academy of Sciences, USA AU - Jayanthi, Subramaniam AU - Deng, Xiaolin AU - Ladenheim, Bruce AU - Mccoy, Michael T AU - Cluster, Andrew AU - Cai, Ning-Sheng AU - Cadet, Jean Lud AD - Molecular Neuropsychiatry Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD Y1 - 2005/01/18/ PY - 2005 DA - 2005 Jan 18 SP - 868 EP - 873 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 102 IS - 3 SN - 0027-8424, 0027-8424 KW - CSA Neurosciences Abstracts; Calcium & Calcified Tissue Abstracts; Toxicology Abstracts KW - T 20029:Enzymes 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/17621577?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Calcineurin%2FNFAT-induced+up-regulation+of+the+Fas+ligand%2FFas+death+pathway+is+involved+in+methamphetamine-induced+neuronal+apoptosis&rft.au=Jayanthi%2C+Subramaniam%3BDeng%2C+Xiaolin%3BLadenheim%2C+Bruce%3BMccoy%2C+Michael+T%3BCluster%2C+Andrew%3BCai%2C+Ning-Sheng%3BCadet%2C+Jean+Lud&rft.aulast=Jayanthi&rft.aufirst=Subramaniam&rft.date=2005-01-18&rft.volume=102&rft.issue=3&rft.spage=868&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-05-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Conformational sampling of the botulinum neurotoxin serotype A light chain: implications for inhibitor binding. AN - 67350597; 15598556 AB - Botulinum neurotoxins (BoNTs) are the most potent of the known biological toxins, and consequently are listed as category A biowarfare agents. Currently, the only treatments against BoNTs include preventative antitoxins and long-term supportive care. Consequently, there is an urgent need for therapeutics to counter these enzymes--post exposure. In a previous study, we identified a number of small, nonpeptidic lead inhibitors of BoNT serotype A light chain (BoNT/A LC) metalloprotease activity, and we identified a common pharmacophore for these molecules. In this study, we have focused on how the dynamic movement of amino acid residues in and surrounding the substrate binding cleft of the BoNT/A LC might affect inhibitor binding modes. The X-ray crystal structures of two BoNT/A LCs (PDB refcodes=3BTA and 1E1H) were examined. Results from these analyses indicate that the core structural features of the examined BoNT/A LCs, including alpha-helices and beta-sheets, remained relatively unchanged during 1 ns dynamics trajectories. However, conformational flexibility was observed in surface loops bordering the substrate binding clefts in both examined structures. Our analyses indicate that these loops may possess the ability to decrease the solvent accessibility of the substrate binding cleft, while at the same time creating new residue contacts for the inhibitors. Loop movements and conformational/positional analyses of residues within the substrate binding cleft are discussed with respect to BoNT/A LC inhibitor binding and our common pharmacophore for inhibition. The results from these studies may aid in the future identification/development of more potent small molecule inhibitors that take advantage of new binding contacts in the BoNT/A LC. JF - Bioorganic & medicinal chemistry AU - Burnett, James C AU - Schmidt, James J AU - McGrath, Connor F AU - Nguyen, Tam L AU - Hermone, Ann R AU - Panchal, Rekha G AU - Vennerstrom, Jonathan L AU - Kodukula, Krishna AU - Zaharevitz, Daniel W AU - Gussio, Rick AU - Bavari, Sina AD - Developmental Therapeutics Program, NCI Frederick, Frederick, MD 21702, USA. Y1 - 2005/01/17/ PY - 2005 DA - 2005 Jan 17 SP - 333 EP - 341 VL - 13 IS - 2 SN - 0968-0896, 0968-0896 KW - Isoquinolines KW - 0 KW - Naphthalenes KW - Protein Subunits KW - Quinolines KW - michellamine A KW - 137793-81-8 KW - Silver KW - 3M4G523W1G KW - Metalloproteases KW - EC 3.4.- KW - Botulinum Toxins, Type A KW - EC 3.4.24.69 KW - Index Medicus KW - Silver -- chemistry KW - Molecular Structure KW - Quinolines -- chemistry KW - Isoquinolines -- chemistry KW - Naphthalenes -- chemistry KW - Metalloproteases -- antagonists & inhibitors KW - Models, Molecular KW - Protein Binding KW - Structure-Activity Relationship KW - Protein Conformation KW - Botulinum Toxins, Type A -- metabolism KW - Botulinum Toxins, Type A -- antagonists & inhibitors KW - Botulinum Toxins, Type A -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67350597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Conformational+sampling+of+the+botulinum+neurotoxin+serotype+A+light+chain%3A+implications+for+inhibitor+binding.&rft.au=Burnett%2C+James+C%3BSchmidt%2C+James+J%3BMcGrath%2C+Connor+F%3BNguyen%2C+Tam+L%3BHermone%2C+Ann+R%3BPanchal%2C+Rekha+G%3BVennerstrom%2C+Jonathan+L%3BKodukula%2C+Krishna%3BZaharevitz%2C+Daniel+W%3BGussio%2C+Rick%3BBavari%2C+Sina&rft.aulast=Burnett&rft.aufirst=James&rft.date=2005-01-17&rft.volume=13&rft.issue=2&rft.spage=333&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 - 2005-05-24 N1 - Date created - 2004-12-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisense suppression of the chloride intracellular channel family induces apoptosis, enhances tumor necrosis factor {alpha}-induced apoptosis, and inhibits tumor growth. AN - 67410554; 15695400 AB - mtCLIC/CLIC4 is a p53 and tumor necrosis factor alpha (TNFalpha) regulated intracellular chloride channel protein that localizes to cytoplasm and organelles and induces apoptosis when overexpressed in several cell types of mouse and human origin. CLIC4 is elevated during TNFalpha-induced apoptosis in human osteosarcoma cell lines. In contrast, inhibition of NFkappaB results in an increase in TNFalpha-mediated apoptosis with a decrease in CLIC4 protein levels. Cell lines expressing an inducible CLIC4-antisense construct that also reduces the expression of several other chloride intracellular channel (CLIC) family proteins were established in the human osteosarcoma lines SaOS and U2OS cells and a malignant derivative of the mouse squamous papilloma line SP1. Reduction of CLIC family proteins by antisense expression caused apoptosis in these cells. Moreover, CLIC4-antisense induction increased TNFalpha-mediated apoptosis in both the SaOS and U2OS derivative cell lines without altering TNFalpha-induced NFkappaB activity. Reducing CLIC proteins in tumor grafts of SP1 cells expressing a tetracycline-regulated CLIC4-antisense substantially inhibited tumor growth and induced tumor apoptosis. Administration of TNFalpha i.p. modestly enhanced the antitumor effect of CLIC reduction in vivo. These results suggest that CLIC proteins could serve as drug targets for cancer therapy, and reduction of CLIC proteins could enhance the activity of other anticancer drugs. JF - Cancer research AU - Suh, Kwang S AU - Mutoh, Michihiro AU - Gerdes, Michael AU - Crutchley, John M AU - Mutoh, Tomoko AU - Edwards, Lindsay E AU - Dumont, Rebecca A AU - Sodha, Pooja AU - Cheng, Christina AU - Glick, Adam AU - Yuspa, Stuart H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2005/01/15/ PY - 2005 DA - 2005 Jan 15 SP - 562 EP - 571 VL - 65 IS - 2 SN - 0008-5472, 0008-5472 KW - CLIC4 protein, human KW - 0 KW - Chloride Channels KW - DNA, Antisense KW - NF-kappa B KW - Tumor Necrosis Factor-alpha KW - Index Medicus KW - Animals KW - Cattle KW - Transfection KW - Humans KW - Xenograft Model Antitumor Assays KW - Mice, Nude KW - Mice KW - Cell Line, Tumor KW - Cell Growth Processes -- genetics KW - Apoptosis -- physiology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Osteosarcoma -- pathology KW - Bone Neoplasms -- pathology KW - DNA, Antisense -- genetics KW - Apoptosis -- genetics KW - Apoptosis -- drug effects KW - Osteosarcoma -- genetics KW - Bone Neoplasms -- therapy KW - Chloride Channels -- antagonists & inhibitors KW - Osteosarcoma -- therapy KW - Chloride Channels -- genetics KW - Bone Neoplasms -- genetics KW - NF-kappa B -- antagonists & inhibitors KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67410554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Antisense+suppression+of+the+chloride+intracellular+channel+family+induces+apoptosis%2C+enhances+tumor+necrosis+factor+%7Balpha%7D-induced+apoptosis%2C+and+inhibits+tumor+growth.&rft.au=Suh%2C+Kwang+S%3BMutoh%2C+Michihiro%3BGerdes%2C+Michael%3BCrutchley%2C+John+M%3BMutoh%2C+Tomoko%3BEdwards%2C+Lindsay+E%3BDumont%2C+Rebecca+A%3BSodha%2C+Pooja%3BCheng%2C+Christina%3BGlick%2C+Adam%3BYuspa%2C+Stuart+H&rft.aulast=Suh&rft.aufirst=Kwang&rft.date=2005-01-15&rft.volume=65&rft.issue=2&rft.spage=562&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 - 2005-03-02 N1 - Date created - 2005-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of hypoxia on radiation-responsive stress-activated protein kinase, p53, and caspase 3 signals in TK6 human lymphoblastoid cells. AN - 67409504; 15695402 AB - Despite significant evidence of a role of hypoxia in cellular resistance to ionizing radiation-induced toxicity, the underlying molecular mechanisms remain unclear. This study focused on the influence of hypoxia on radiation-induced signals in TK6 human lymphoblastoid cells. Hypoxic (<10 ppm oxygen) and aerobic cells were exposed to equilethal doses of ionizing radiation, radiation dose ratio, 3:1 (hypoxia:air). Hypoxia alone or radiation treatment under aerobic or hypoxic conditions led to increased levels of phospho-p44/42 mitogen-activated protein kinase. Levels of phospho-p38 mitogen-activated protein kinase did not change as a result of either hypoxia or irradiation. Hypoxia alone had no effect on expression of phospho-stress-activated protein kinase (SAPK), wild-type p53, or cleaved caspase 3. Irradiation under aerobic conditions resulted in an increase in the phospho-SAPK signal, whereas hypoxia suppressed the irradiation-induced increase in the level of phospho-SAPK. Both hypoxic and aerobic cells showed increases in p53 levels in response to radiation. Hypoxia blocked radiation-induced cleavage of caspase 3 and poly-ADP-ribose polymerase. Irradiation of aerobic and hypoxic TK6 cells using 6 and 18 Gy, respectively, resulted in a similar and significant increase in fraction of apoptotic cells within 24 hours postirradiation. In contrast, basal levels of apoptosis were observed at 24 hours postirradiation in aerobic and hypoxic NH32 cells, a p53 null derivative of TK6 cells. These results suggest that radiation-induced apoptosis under hypoxia occurs independent of phospho-SAPK and caspase 3, and the p53 response is an obligatory apoptotic signal in TK6 cells. JF - Cancer research AU - Samuni, Ayelet M AU - Kasid, Usha AU - Chuang, Eric Y AU - Suy, Simeng AU - Degraff, William AU - Krishna, Murali C AU - Russo, Angelo AU - Mitchell, James B AD - Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 2005/01/15/ PY - 2005 DA - 2005 Jan 15 SP - 579 EP - 586 VL - 65 IS - 2 SN - 0008-5472, 0008-5472 KW - Tumor Suppressor Protein p53 KW - 0 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Phosphorylation -- radiation effects KW - Humans KW - Apoptosis -- physiology KW - Apoptosis -- radiation effects KW - Cell Hypoxia -- physiology KW - Flow Cytometry KW - Aerobiosis KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Cell Line KW - Mitogen-Activated Protein Kinase 1 -- radiation effects KW - Tumor Suppressor Protein p53 -- biosynthesis KW - MAP Kinase Signaling System -- physiology KW - Lymphocytes -- metabolism KW - Mitogen-Activated Protein Kinase 3 -- radiation effects KW - Caspases -- radiation effects KW - Tumor Suppressor Protein p53 -- metabolism KW - Caspases -- metabolism KW - Mitogen-Activated Protein Kinase 3 -- metabolism KW - Mitogen-Activated Protein Kinase 1 -- metabolism KW - MAP Kinase Signaling System -- radiation effects KW - Lymphocytes -- enzymology KW - Lymphocytes -- radiation effects KW - Tumor Suppressor Protein p53 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67409504?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effects+of+hypoxia+on+radiation-responsive+stress-activated+protein+kinase%2C+p53%2C+and+caspase+3+signals+in+TK6+human+lymphoblastoid+cells.&rft.au=Samuni%2C+Ayelet+M%3BKasid%2C+Usha%3BChuang%2C+Eric+Y%3BSuy%2C+Simeng%3BDegraff%2C+William%3BKrishna%2C+Murali+C%3BRusso%2C+Angelo%3BMitchell%2C+James+B&rft.aulast=Samuni&rft.aufirst=Ayelet&rft.date=2005-01-15&rft.volume=65&rft.issue=2&rft.spage=579&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 - 2005-03-02 N1 - Date created - 2005-02-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pesticide use and breast cancer risk among farmers' wives in the agricultural health study. AN - 67339839; 15632262 AB - The authors examined the association between pesticide use and breast cancer incidence among farmers' wives in a large prospective cohort study in Iowa and North Carolina. Participants were 30,454 women with no history of breast cancer prior to cohort enrollment in 1993-1997. Information on pesticide use and other information was obtained by self-administered questionnaire at enrollment from the women and their husbands. Through 2000, 309 incident breast cancer cases were identified via population-based cancer registries. Rate ratios were calculated for individual pesticides using Poisson regression, controlling for confounding factors. Breast cancer standardized incidence ratios were 0.87 (95% confidence interval: 0.74, 1.02) for women who reported ever applying pesticides and 1.05 (95% confidence interval: 0.89, 1.24) for women who reported never applying pesticides. There was some evidence of increased risk associated with use of 2,4,5-trichloro-phenoxypropionic acid (2,4,5-TP) and possibly use of dieldrin, captan, and 2,4,5-trichlorophenoxyacetic acid (2,4,5-TP), but small numbers of cases among those who had personally used the pesticides precluded firm conclusions. The authors found no clear association of breast cancer risk with farm size or washing of clothes worn during pesticide application, but risk was modestly elevated among women whose homes were closest to areas of pesticide application. Further follow-up of this cohort should help clarify the relation between pesticide exposure and breast cancer risk. JF - American journal of epidemiology AU - Engel, Lawrence S AU - Hill, Deirdre A AU - Hoppin, Jane A AU - Lubin, Jay H AU - Lynch, Charles F AU - Pierce, Joy AU - Samanic, Claudine AU - Sandler, Dale P AU - Blair, Aaron AU - Alavanja, Michael C AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. engell@mskcc.org Y1 - 2005/01/15/ PY - 2005 DA - 2005 Jan 15 SP - 121 EP - 135 VL - 161 IS - 2 SN - 0002-9262, 0002-9262 KW - Pesticides KW - 0 KW - Index Medicus KW - Reproductive History KW - Humans KW - Aged KW - Iowa KW - Life Style KW - Prospective Studies KW - Aged, 80 and over KW - Risk Factors KW - Adult KW - North Carolina KW - Follow-Up Studies KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Agricultural Workers' Diseases -- chemically induced KW - Occupational Exposure -- adverse effects KW - Breast Neoplasms -- chemically induced KW - Pesticides -- adverse effects KW - Spouses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67339839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pesticide+use+and+breast+cancer+risk+among+farmers%27+wives+in+the+agricultural+health+study.&rft.au=Engel%2C+Lawrence+S%3BHill%2C+Deirdre+A%3BHoppin%2C+Jane+A%3BLubin%2C+Jay+H%3BLynch%2C+Charles+F%3BPierce%2C+Joy%3BSamanic%2C+Claudine%3BSandler%2C+Dale+P%3BBlair%2C+Aaron%3BAlavanja%2C+Michael+C&rft.aulast=Engel&rft.aufirst=Lawrence&rft.date=2005-01-15&rft.volume=161&rft.issue=2&rft.spage=121&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 - 2005-02-25 N1 - Date created - 2005-01-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protective effect of dextromethorphan against endotoxic shock in mice. AN - 67335548; 15627475 AB - Dextromethorphan (DM) is a dextrorotatory morphinan and an over-the-counter non-opioid cough suppressant. We have previously shown that DM protects against LPS-induced dopaminergic neurodegeneration through inhibition of microglia activation. Here, we investigated protective effects of DM against endotoxin shock induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice and the mechanism underlying its protective effect. Mice were given multiple injections of DM (12.5 mg/kg, s.c.) 30 min before and 2, 4 h after an injection of LPS/GalN (20 microg/700 mg/kg). DM administration decreased LPS/GalN-induced mortality and hepatotoxicity, as evidenced by increased survival rate, decreased serum alanine aminotransferase activity and improved pathology. Furthermore, DM was also effective when it was given 30 min after LPS/GalN injection. The protection was likely associated with reduced serum and liver tumor necrosis factor alpha (TNF-alpha) levels. DM also attenuated production of superoxide and intracellular reactive oxygen species in Kupffer cells and neutrophils. Real-time RT-PCR analysis revealed that DM administration suppressed the expression of a variety of inflammation-related genes such as macrophage inflammatory protein-2, CXC chemokine, thrombospondin-1, intercellular adhesion molecular-1 and interleukin-6. DM also decreased the expression of genes related to cell-death pathways, such as the DNA damage protein genes GADD45 and GADD153. In summary, DM is effective in protecting mice against LPS/GalN-induced hepatotoxicity, and the mechanism is likely through a faster TNF-alpha clearance, and decrease of superoxide production and inflammation and cell-death related components. This study not only extends neuroprotective effect of DM, but also suggests that DM may be a novel compound for the therapeutic intervention for sepsis. JF - Biochemical pharmacology AU - Li, Guorong AU - Liu, Yuxin AU - Tzeng, Nian-ssheng AU - Cui, Gang AU - Block, Michelle L AU - Wilson, Belinda AU - Qin, Liya AU - Wang, Tongguang AU - Liu, Bin AU - Liu, Jie AU - Hong, Jau-Shyong AD - Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, NCI, National Institute of Environmental Health Sciences, National Institutes of Health Sciences, Research Triangle Park, NC 27709, USA. guorong1@med.unc.edu Y1 - 2005/01/15/ PY - 2005 DA - 2005 Jan 15 SP - 233 EP - 240 VL - 69 IS - 2 SN - 0006-2952, 0006-2952 KW - Immunosuppressive Agents KW - 0 KW - Lipopolysaccharides KW - Reactive Oxygen Species KW - Dextromethorphan KW - 7355X3ROTS KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Liver -- drug effects KW - Cells, Cultured KW - Mice, Inbred C57BL KW - Liver -- metabolism KW - Lipopolysaccharides -- toxicity KW - Kupffer Cells -- metabolism KW - Kupffer Cells -- drug effects KW - Mice KW - Male KW - Mice, Knockout KW - Shock, Septic -- chemically induced KW - Dextromethorphan -- pharmacology KW - Dextromethorphan -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use KW - Shock, Septic -- prevention & control KW - Shock, Septic -- metabolism KW - Immunosuppressive Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67335548?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Protective+effect+of+dextromethorphan+against+endotoxic+shock+in+mice.&rft.au=Li%2C+Guorong%3BLiu%2C+Yuxin%3BTzeng%2C+Nian-ssheng%3BCui%2C+Gang%3BBlock%2C+Michelle+L%3BWilson%2C+Belinda%3BQin%2C+Liya%3BWang%2C+Tongguang%3BLiu%2C+Bin%3BLiu%2C+Jie%3BHong%2C+Jau-Shyong&rft.aulast=Li&rft.aufirst=Guorong&rft.date=2005-01-15&rft.volume=69&rft.issue=2&rft.spage=233&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 - 2005-02-18 N1 - Date created - 2005-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of cytomegalovirus (CMV) DNA by polymerase chain reaction is associated with hearing loss in newborns with symptomatic congenital CMV infection involving the central nervous system. AN - 67332364; 15609232 AB - The study sought to determine the relationship between cytomegalovirus (CMV) viremia during early infancy and clinical and laboratory outcome events, particularly hearing loss in infants with symptomatic congenital CMV infection involving the central nervous system (CNS). A total of 147 infant patients were enrolled prospectively in 2 clinical trials evaluating ganciclovir for the treatment of symptomatic congenital CMV infection involving the CNS. Aliquots of serum collected at enrollment in either of the 2 trials were available from 50 of the infants, and the degree of viremia was determined by real-time quantitative polymerase chain reaction. Of the 50 infants from whom serum samples were available, 37 had detectable CMV DNA in the serum sample collected at enrollment and were classified as viremic. Viremic infants were more likely to have (1) hearing loss both at enrollment (P = .045) and at the 6-month follow-up testing (P = .035) and (2) other indicators of active CMV disease, including elevated levels of alanine aminotransferase, petechial rash, and organomegaly. In children with symptomatic congenital CMV infection involving the CNS, viremia during early infancy is associated with hearing loss and systemic CMV disease. JF - The Journal of infectious diseases AU - Bradford, Russell D AU - Cloud, Gretchen AU - Lakeman, Alfred D AU - Boppana, Suresh AU - Kimberlin, David W AU - Jacobs, Richard AU - Demmler, Gail AU - Sanchez, Pablo AU - Britt, William 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, AL 35233, USA. ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group Y1 - 2005/01/15/ PY - 2005 DA - 2005 Jan 15 SP - 227 EP - 233 VL - 191 IS - 2 SN - 0022-1899, 0022-1899 KW - DNA, Viral KW - 0 KW - Ganciclovir KW - P9G3CKZ4P5 KW - Abridged Index Medicus KW - Index Medicus KW - Infant KW - Polymerase Chain Reaction KW - Ganciclovir -- therapeutic use KW - Ganciclovir -- administration & dosage KW - Humans KW - Infant, Newborn KW - Ganciclovir -- adverse effects KW - Hearing Loss -- virology KW - Hearing Loss -- epidemiology KW - Cytomegalovirus Infections -- congenital KW - Cytomegalovirus Infections -- complications KW - Central Nervous System Diseases -- virology KW - Cytomegalovirus -- genetics KW - DNA, Viral -- blood KW - DNA, Viral -- isolation & purification KW - Cytomegalovirus -- isolation & purification KW - Hearing Loss -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67332364?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Detection+of+cytomegalovirus+%28CMV%29+DNA+by+polymerase+chain+reaction+is+associated+with+hearing+loss+in+newborns+with+symptomatic+congenital+CMV+infection+involving+the+central+nervous+system.&rft.au=Bradford%2C+Russell+D%3BCloud%2C+Gretchen%3BLakeman%2C+Alfred+D%3BBoppana%2C+Suresh%3BKimberlin%2C+David+W%3BJacobs%2C+Richard%3BDemmler%2C+Gail%3BSanchez%2C+Pablo%3BBritt%2C+William%3BSoong%2C+Seng-jaw%3BWhitley%2C+Richard+J%3BNational+Institute+of+Allergy+and+Infectious+Diseases+Collaborative+Antiviral+Study+Group&rft.aulast=Bradford&rft.aufirst=Russell&rft.date=2005-01-15&rft.volume=191&rft.issue=2&rft.spage=227&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 - 2005-03-21 N1 - Date created - 2004-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of hydrogen peroxide-induced Cu,Zn-superoxide dismutase-centered radical formation as explored by immuno-spin trapping: the role of copper- and carbonate radical anion-mediated oxidations. AN - 67330661; 15607903 AB - We have reinvestigated the biochemistry of H2O2-induced Cu,Zn-superoxide dismutase (SOD1)-centered radicals, detecting them by immuno-spin trapping. These radicals are involved in H2O2-induced structural and functional damage to SOD1, and their mechanism of generation depends on copper and/or (bi)carbonate (i.e., CO2, CO3(-2), or HCO3-). First, in the absence of DTPA and (bi)carbonate, Cu(II) was partially released and rebound at His, Cys, and Tyr residues in SOD1 with the generation of protein-copper-bound oxidants outside the SOD1 active site by reaction with excess H2O2. These species produced immuno-spin trapping-detectable SOD1-centered radicals associated with H2O2-induced active site ( approximately 5 and approximately 10 kDa fragments) and non-active site (smearing between 3 and 16 kDa) copper-dependent backbone oxidations and subsequent fragmentation of SOD1. Second, in the presence of DTPA, which inhibits H2O2-induced SOD1 non-active site fragmentation, (bi)carbonate scavenged the enzyme-bound oxidant at the SOD1 active site to produce the carbonate radical anion, CO3*-, thus protecting against active site SOD1 fragmentation. CO3*- diffuses and produces side chain oxidations forming DMPO-trappable radical sites outside the enzyme active site. Both mechanisms for generating immuno-spin trapping-detectable SOD1-centered radicals were susceptible to inhibition by cyanide and enhanced at high pH values. In addition, (bi)carbonate enhanced H2O2-induced SOD1 turnover as demonstrated by an enhancement in oxygen evolution and SOD1 inactivation. These results help clarify the free radical chemistry involved in the functional and structural oxidative damage to SOD1 by H2O2 with the intermediacy of copper- and CO3*--mediated oxidations. JF - Free radical biology & medicine AU - Ramirez, Dario C AU - Gomez Mejiba, Sandra E AU - Mason, Ronald P AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA. ramirez1@niehs.nih.gov Y1 - 2005/01/15/ PY - 2005 DA - 2005 Jan 15 SP - 201 EP - 214 VL - 38 IS - 2 SN - 0891-5849, 0891-5849 KW - Anions KW - 0 KW - Free Radicals KW - Oxidants KW - Superoxides KW - 11062-77-4 KW - Tyrosine KW - 42HK56048U KW - Histidine KW - 4QD397987E KW - Carbon KW - 7440-44-0 KW - Copper KW - 789U1901C5 KW - Pentetic Acid KW - 7A314HQM0I KW - dityrosine KW - 980-21-2 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Cysteine KW - K848JZ4886 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Hydrogen-Ion Concentration KW - Pentetic Acid -- chemistry KW - Binding Sites KW - Oxidation-Reduction KW - Histidine -- chemistry KW - Superoxides -- chemistry KW - Blotting, Western KW - Cattle KW - Cysteine -- chemistry KW - Spin Trapping KW - Oxidants -- chemistry KW - Enzyme-Linked Immunosorbent Assay KW - Models, Chemical KW - Time Factors KW - Catalase -- chemistry KW - DNA Fragmentation KW - Tyrosine -- chemistry KW - Oxygen -- metabolism KW - Hydrogen Peroxide -- pharmacology KW - Copper -- metabolism KW - Superoxide Dismutase -- metabolism KW - Superoxide Dismutase -- chemistry KW - Oxygen -- chemistry KW - Tyrosine -- analogs & derivatives KW - Carbon -- chemistry KW - Copper -- chemistry KW - Hydrogen Peroxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67330661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mechanism+of+hydrogen+peroxide-induced+Cu%2CZn-superoxide+dismutase-centered+radical+formation+as+explored+by+immuno-spin+trapping%3A+the+role+of+copper-+and+carbonate+radical+anion-mediated+oxidations.&rft.au=Ramirez%2C+Dario+C%3BGomez+Mejiba%2C+Sandra+E%3BMason%2C+Ronald+P&rft.aulast=Ramirez&rft.aufirst=Dario&rft.date=2005-01-15&rft.volume=38&rft.issue=2&rft.spage=201&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 - 2005-05-19 N1 - Date created - 2004-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin gamma1 in human glioblastoma cells. AN - 67262447; 15561105 AB - The induction of cyclooxygenase-2 (COX-2) expression is associated with more aggressive gliomas and poor survival. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX activity and have antitumorigenic properties. In this report, our initial aim was to determine if indomethacin would alter gene expression as measured by suppression subtractive hybridization (SSH). Three up-regulated and four down-regulated genes by indomethacin treatment were identified. Laminin gamma1, an extracellular matrix molecule, was the most significantly repressed gene. The repression of laminin gamma1 by indomethacin was confirmed by Northern and Western blot analyses and occurred in a concentration- and time-dependent manner at the protein level. Among several NSAIDs tested, only sulindac sulfide and indomethacin suppressed laminin gamma1 protein expression, and this repression was observed in both COX-expressing and -deficient cell lines, suggesting that laminin gamma1 repression by COX inhibitors was independent of COX. Indomethacin, at a concentration that represses laminin gamma1, inhibited glioblastoma cell invasion that was partially restored with additional human laminin protein containing gamma1 chain. The repression of laminin gamma1 by NSAIDs may be related to attenuation of invasion of brain tumors. These findings are important in understanding the chemopreventive activity of some NSAIDs and could be relevant for designing therapeutic strategies against glioblastoma. JF - Experimental cell research AU - Ishibashi, Minako AU - Bottone, Frank G AU - Taniura, Seijiro AU - Kamitani, Hideki AU - Watanabe, Takashi AU - Eling, Thomas E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA. Y1 - 2005/01/15/ PY - 2005 DA - 2005 Jan 15 SP - 244 EP - 252 VL - 302 IS - 2 SN - 0014-4827, 0014-4827 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Antineoplastic Agents KW - Antineoplastic Agents, Phytogenic KW - Cyclooxygenase Inhibitors KW - Laminin KW - Pyrazoles KW - SC 560 KW - laminin gamma 1 KW - 1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole KW - 162054-19-5 KW - Sulindac KW - 184SNS8VUH KW - Etoposide KW - 6PLQ3CP4P3 KW - sulindac sulfide KW - 6UVA8S2DEY KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - Etoposide -- pharmacology KW - Pyrazoles -- pharmacology KW - Blotting, Western KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Dose-Response Relationship, Drug KW - Kinetics KW - Humans KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Cell Line, Tumor KW - Reverse Transcriptase Polymerase Chain Reaction KW - Antineoplastic Agents -- pharmacology KW - Densitometry KW - Laminin -- metabolism KW - Laminin -- drug effects KW - Sulindac -- pharmacology KW - Sulindac -- analogs & derivatives KW - Glioblastoma -- drug therapy KW - Glioblastoma -- enzymology KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Indomethacin -- 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/67262447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+cyclooxygenase+inhibitor+indomethacin+modulates+gene+expression+and+represses+the+extracellular+matrix+protein+laminin+gamma1+in+human+glioblastoma+cells.&rft.au=Ishibashi%2C+Minako%3BBottone%2C+Frank+G%3BTaniura%2C+Seijiro%3BKamitani%2C+Hideki%3BWatanabe%2C+Takashi%3BEling%2C+Thomas+E&rft.aulast=Ishibashi&rft.aufirst=Minako&rft.date=2005-01-15&rft.volume=302&rft.issue=2&rft.spage=244&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 - 2005-01-11 N1 - Date created - 2004-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interlaboratory Comparability Study of Cancer Gene Expression Analysis Using Oligonucleotide Microarrays AN - 19939003; 6166336 AB - A key step in bringing gene expression data into clinical practice is the conduct of large studies to confirm preliminary models. The performance of such confirmatory studies and the transition to clinical practice requires that microarray data from different laboratories are comparable and reproducible. We designed a study to assess the comparability of data from four laboratories that will conduct a larger microarray profiling confirmation project in lung adenocarcinomas. To test the feasibility of combining data across laboratories, frozen tumor tissues, cell line pellets, and purified RNA samples were analyzed at each of the four laboratories. Samples of each type and several subsamples from each tumor and each cell line were blinded before being distributed. The laboratories followed a common protocol for all steps of tissue processing, RNA extraction, and microarray analysis using Affymetrix Human Genome U133A arrays. High within-laboratory and between-laboratory correlations were observed on the purified RNA samples, the cell lines, and the frozen tumor tissues. Intraclass correlation within laboratories was only slightly stronger than between laboratories, and the intraclass correlation tended to be weakest for genes expressed at low levels and showing small variation. Finally, hierarchical cluster analysis revealed that the repeated samples clustered together regardless of the laboratory in which the experiments were done. The findings indicate that under properly controlled conditions it is feasible to perform complete tumor microarray analysis, from tissue processing to hybridization and scanning, at multiple independent laboratories for a single study. JF - Clinical Cancer Research AU - Dobbin, Kevin K AU - Beer, David G AU - Meyerson, Matthew AU - Yeatman, Timothy J AU - Gerald, William L AU - Jacobson, James W AU - Conley, Barbara AU - Buetow, Kenneth H AU - Heiskanen, Mervi AU - Simon, Richard M AU - Minna, John D AU - Girard, Luc AU - Misek, David E AU - Taylor, Jeremy MG AU - Hanash, Samir AU - Naoki, Katsuhiko AU - Hayes, DNeil AU - Ladd-Acosta, Christine AU - Enkemann, Steven A AU - Viale, Agnes AU - Giordano, Thomas J AD - Cancer Diagnosis Program, Biometric Research Branch, and Center for Bioinformatics, National Cancer Institute, Bethesda, Maryland Y1 - 2005/01/15/ PY - 2005 DA - 2005 Jan 15 SP - 565 EP - 572 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 11 IS - 2 SN - 1078-0432, 1078-0432 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Genomes KW - Data processing KW - Tumors KW - Oligonucleotides KW - DNA microarrays KW - Cancer KW - RNA processing KW - Gene expression KW - Tumor cell lines KW - Scanning KW - RNA KW - Lung KW - Controlled conditions KW - Adenocarcinoma KW - G 07730:Development & Cell Cycle KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19939003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Interlaboratory+Comparability+Study+of+Cancer+Gene+Expression+Analysis+Using+Oligonucleotide+Microarrays&rft.au=Dobbin%2C+Kevin+K%3BBeer%2C+David+G%3BMeyerson%2C+Matthew%3BYeatman%2C+Timothy+J%3BGerald%2C+William+L%3BJacobson%2C+James+W%3BConley%2C+Barbara%3BBuetow%2C+Kenneth+H%3BHeiskanen%2C+Mervi%3BSimon%2C+Richard+M%3BMinna%2C+John+D%3BGirard%2C+Luc%3BMisek%2C+David+E%3BTaylor%2C+Jeremy+MG%3BHanash%2C+Samir%3BNaoki%2C+Katsuhiko%3BHayes%2C+DNeil%3BLadd-Acosta%2C+Christine%3BEnkemann%2C+Steven+A%3BViale%2C+Agnes%3BGiordano%2C+Thomas+J&rft.aulast=Dobbin&rft.aufirst=Kevin&rft.date=2005-01-15&rft.volume=11&rft.issue=2&rft.spage=565&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-06-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Genomes; Data processing; Tumors; DNA microarrays; Oligonucleotides; Cancer; Gene expression; RNA processing; Tumor cell lines; RNA; Scanning; Lung; Controlled conditions; Adenocarcinoma ER - TY - JOUR T1 - Neutralizing Antibodies Elicited by Immunization of Monkeys with DNA Plasmids and Recombinant Adenoviral Vectors Expressing Human Immunodeficiency Virus Type 1 Proteins AN - 17863422; 6173525 AB - Immunization with recombinant serotype 5 adenoviral (rAd5) vectors or a combination of DNA plasmid priming and rAd5 boosting is known to elicit potent immune responses. However, little data exist regarding these immunization strategies and the development of anti-human immunodeficiency virus type 1 (HIV- 1) neutralizing antibodies. We used DNA plasmids and rAd5 vectors encoding the HIV-1 89.6P or chimeric HxB2/BaL envelope glycoprotein to immunize macaque monkeys. A single rAd5 immunization elicited anti-Env antibody responses, but there was little boosting with subsequent rAd5 immunizations. In contrast, rAd5 boosting of DNA-primed monkeys resulted in a rapid rise in antibody titers, including the development of anti-HIV-1 neutralizing antibodies. The potency and breadth of neutralization were evaluated by testing plasma against a panel of 14 clade B primary isolates. Moderate levels of plasma neutralizing activity were detected against about one-third of the viruses tested, and immunoglobulin G fractionation demonstrated that virus neutralization was antibody mediated. After a challenge with a chimeric simian-human immunodeficiency virus (SHIV89.6P), an anamnestic neutralizing antibody response was observed, although the breadth of the response was limited to the subset of viruses that were neutralized after the primary immunization. These data are the first detailed description of the anti-HIV-1 neutralizing antibody response in nonhuman primates elicited by DNA and rAd5 immunization. In addition to the well- established ability of DNA priming and rAd5 boosting to elicit potent anti-HIV-1 cellular immune responses, this immunization strategy elicits anti-HIV-1 neutralizing antibodies and therefore can be used to study novel Env immunogens designed to elicit more potent neutralizing antibodies. JF - Journal of Virology AU - Mascola, John R AU - Sambor, Anna AU - Beaudry, Kristin AU - Santra, Sampa AU - Welcher, Brent AU - Louder, Mark K AU - Vancott, Thomas C AU - Huang, Yue AU - Chakrabarti, Bimal K AU - Kong, Wing-Pui AU - Yang, Zhi-Yong AU - Xu, Ling AU - Montefiori, David C AU - Nabel, Gary J AU - Letvin, Norman L AD - Vaccine Research Center, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda. Henry M. Jackson Foundation, Rockville, Maryland. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Duke University Medical Center, Durham, North Carolina Y1 - 2005/01/15/ PY - 2005 DA - 2005 Jan 15 SP - 771 EP - 779 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 79 IS - 2 SN - 0022-538X, 0022-538X KW - HIV-1 KW - Rhesus monkey KW - Rhesus macaque KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Serotypes KW - Expression vectors KW - Envelopes KW - DNA vaccines KW - Human immunodeficiency virus 1 KW - Macaca mulatta KW - Glycoproteins KW - Antibody response KW - Plasmids KW - Primates KW - Immunization KW - Immunoglobulin G KW - N 14025:RNA/DNA role in infection & immune response KW - F 06100:Vaccines - active immunity KW - W3 33345:DNA vaccines KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17863422?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neutralizing+Antibodies+Elicited+by+Immunization+of+Monkeys+with+DNA+Plasmids+and+Recombinant+Adenoviral+Vectors+Expressing+Human+Immunodeficiency+Virus+Type+1+Proteins&rft.au=Mascola%2C+John+R%3BSambor%2C+Anna%3BBeaudry%2C+Kristin%3BSantra%2C+Sampa%3BWelcher%2C+Brent%3BLouder%2C+Mark+K%3BVancott%2C+Thomas+C%3BHuang%2C+Yue%3BChakrabarti%2C+Bimal+K%3BKong%2C+Wing-Pui%3BYang%2C+Zhi-Yong%3BXu%2C+Ling%3BMontefiori%2C+David+C%3BNabel%2C+Gary+J%3BLetvin%2C+Norman+L&rft.aulast=Mascola&rft.aufirst=John&rft.date=2005-01-15&rft.volume=79&rft.issue=2&rft.spage=771&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Primates; Macaca mulatta; Immunization; DNA vaccines; Plasmids; Expression vectors; Antibody response; Serotypes; Immunoglobulin G; Glycoproteins; Envelopes ER - TY - JOUR T1 - Genomewide Analysis of Gene Expression in Staphylococcus epidermidis Biofilms: Insights into the Pathophysiology of S. epidermidis Biofilms and the Role of Phenol-Soluble Modulins in Formation of Biofilms AN - 17798557; 6129628 AB - Many bacterial pathogens form cellular agglomerations known as biofilms, which considerably limit the success of both antibiotic treatment and the human immune defense. To gain insight into the pathophysiology of the leading nosocomial pathogen, Staphylococcus epidermidis, we analyzed the genome of biofilm-forming S. epidermidis, constructed a microarray representing its entire transcriptome, and performed expression profiling of an S. epidermidis biofilm. Gene-regulated processes in the biofilm led to a nonaggressive and protected form of bacterial growth with low metabolic activity, which is optimally suited to guarantee long-term survival during chronic infection. A class of peptides known as phenol-soluble modulins, which combine proinflammatory activity with a putative role in detachment of biofilms, evolved as potential key determinants controlling the switch between aggressive and quiescent modes of infection. Our data suggest that S. epidermidis adjusts its lifestyle to varying requirements during colonization and infection by means of an expansive change of gene expression. The observed physiological characteristics of the biofilm mode of growth--in particular, the contribution of surfactant-like peptides--might serve as a model for a variety of biofilm-forming pathogens. JF - Journal of Infectious Diseases AU - Yao, Y AU - Sturdevant, DE AU - Otto, M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA Y1 - 2005/01/15/ PY - 2005 DA - 2005 Jan 15 SP - 289 EP - 298 VL - 191 IS - 2 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts B: Bacteriology KW - Genomes KW - Survival KW - Antibiotics KW - Pathogens KW - DNA microarrays KW - Inflammation KW - Gene expression KW - Colonization KW - Chronic infection KW - Biofilms KW - Staphylococcus epidermidis KW - Agglomeration 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/17798557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genomewide+Analysis+of+Gene+Expression+in+Staphylococcus+epidermidis+Biofilms%3A+Insights+into+the+Pathophysiology+of+S.+epidermidis+Biofilms+and+the+Role+of+Phenol-Soluble+Modulins+in+Formation+of+Biofilms&rft.au=Yao%2C+Y%3BSturdevant%2C+DE%3BOtto%2C+M&rft.aulast=Yao&rft.aufirst=Y&rft.date=2005-01-15&rft.volume=191&rft.issue=2&rft.spage=289&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; Biofilms; Pathogens; Gene expression; DNA microarrays; Colonization; Survival; Agglomeration; Inflammation; Chronic infection; Antibiotics; Genomes ER - TY - JOUR T1 - Self-reported Electrical Appliance Use and Risk of Adult Brain Tumors AN - 17483282; 6164741 AB - Electrical appliances produce the highest intensity exposures to residential extremely low frequency electromagnetic fields. The authors investigated whether appliances may be associated with adult brain tumors in a hospital-based case-control study at three centers in the United States from 1994 to 1998. A total of 410 glioma, 178 meningioma, and 90 acoustic neuroma cases and 686 controls responded to a self-administered questionnaire about 14 electrical appliances. There was little evidence of association between brain tumors and curling iron, heating pad, vibrating massager, electric blanket, heated water bed, sound system, computer, television, humidifier, microwave oven, and electric stove. Ever use of hair dryers was associated with glioma (odds ratio = 1.7, 95% confidence interval: 1.1, 2.5), but there was no evidence of increasing risk with increasing amount of use. In men, meningioma was associated with electric shaver use (odds ratio = 10.9, 95% confidence interval: 2.3, 50), and odds ratios increased with cumulative minutes of use, although they were based on only two nonexposed cases. Recall bias for appliances used regularly near the head or chance may provide an alternative explanation for the observed associations. Overall, results indicate that extremely low frequency electromagnetic fields from commonly used household appliances are unlikely to increase the risk of brain tumors. JF - American Journal of Epidemiology AU - Kleinerman, Ruth A AU - Linet, Martha S AU - Hatch, Elizabeth E AU - Tarone, Robert E AU - Black, Peter M AU - Selker, Robert G AU - Shapiro, William R AU - Fine, Howard A AU - Inskip, Peter D AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD. Y1 - 2005/01/15/ PY - 2005 DA - 2005 Jan 15 SP - 136 EP - 146 PB - Oxford University Press, Oxford Journals Health, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 161 IS - 2 SN - 0002-9262, 0002-9262 KW - tumors KW - electrical appliances KW - Risk Abstracts; CSA Neurosciences Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - Consumer products KW - Public health KW - Glioma KW - Head KW - Acoustics KW - Computers KW - Microwave oven KW - Brain KW - Electromagnetic fields KW - Brain tumors KW - Humidifiers KW - Iron KW - meningioma KW - X 24210:Radiation & radioactive materials KW - H 8000:Radiation Safety/Electrical Safety KW - N3 11129:Neural and glial oncology KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17483282?accountid=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=Self-reported+Electrical+Appliance+Use+and+Risk+of+Adult+Brain+Tumors&rft.au=Kleinerman%2C+Ruth+A%3BLinet%2C+Martha+S%3BHatch%2C+Elizabeth+E%3BTarone%2C+Robert+E%3BBlack%2C+Peter+M%3BSelker%2C+Robert+G%3BShapiro%2C+William+R%3BFine%2C+Howard+A%3BInskip%2C+Peter+D&rft.aulast=Kleinerman&rft.aufirst=Ruth&rft.date=2005-01-15&rft.volume=161&rft.issue=2&rft.spage=136&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 - Consumer products; Electromagnetic fields; Brain; Public health; Brain tumors; meningioma; Glioma; Head; Humidifiers; Iron; Microwave oven; Computers; Acoustics ER - TY - JOUR T1 - Self-propagating, molecular-level polymorphism in Alzheimer's beta-amyloid fibrils. AN - 67380725; 15653506 AB - Amyloid fibrils commonly exhibit multiple distinct morphologies in electron microscope and atomic force microscope images, often within a single image field. By using electron microscopy and solid-state nuclear magnetic resonance measurements on fibrils formed by the 40-residue beta-amyloid peptide of Alzheimer's disease (Abeta(1-40)), we show that different fibril morphologies have different underlying molecular structures, that the predominant structure can be controlled by subtle variations in fibril growth conditions, and that both morphology and molecular structure are self-propagating when fibrils grow from preformed seeds. Different Abeta(1-40) fibril morphologies also have significantly different toxicities in neuronal cell cultures. These results have implications for the mechanism of amyloid formation, the phenomenon of strains in prion diseases, the role of amyloid fibrils in amyloid diseases, and the development of amyloid-based nano-materials. JF - Science (New York, N.Y.) AU - Petkova, Aneta T AU - Leapman, Richard D AU - Guo, Zhihong AU - Yau, Wai-Ming AU - Mattson, Mark P AU - Tycko, Robert AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD 20892-0520, USA. Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 SP - 262 EP - 265 VL - 307 IS - 5707 KW - Amyloid beta-Peptides KW - 0 KW - Peptide Fragments KW - amyloid beta-protein (1-40) KW - Index Medicus KW - Molecular Structure KW - Animals KW - Protein Structure, Secondary KW - Chemistry, Physical KW - Neurons -- drug effects KW - Humans KW - Rats KW - Microscopy, Electron, Transmission KW - Amino Acid Motifs KW - Cells, Cultured KW - Nuclear Magnetic Resonance, Biomolecular KW - Chemical Phenomena KW - Hippocampus -- cytology KW - Neurons -- cytology KW - Microscopy, Atomic Force KW - Hydrogen Bonding KW - Protein Conformation KW - Peptide Fragments -- toxicity KW - Peptide Fragments -- chemistry KW - Amyloid beta-Peptides -- ultrastructure KW - Amyloid beta-Peptides -- toxicity KW - Amyloid beta-Peptides -- chemistry KW - Peptide Fragments -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67380725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Self-propagating%2C+molecular-level+polymorphism+in+Alzheimer%27s+beta-amyloid+fibrils.&rft.au=Petkova%2C+Aneta+T%3BLeapman%2C+Richard+D%3BGuo%2C+Zhihong%3BYau%2C+Wai-Ming%3BMattson%2C+Mark+P%3BTycko%2C+Robert&rft.aulast=Petkova&rft.aufirst=Aneta&rft.date=2005-01-14&rft.volume=307&rft.issue=5707&rft.spage=262&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 - 2005-02-02 N1 - Date created - 2005-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of Rho/ROCK and p38 MAP kinase pathways in transforming growth factor-beta-mediated Smad-dependent growth inhibition of human breast carcinoma cells in vivo. AN - 67367290; 15520018 AB - TGF-beta is a multifunctional cytokine known to exert its biological effects through a variety of signaling pathways of which Smad signaling is considered to be the main mediator. At present, the Smad-independent pathways, their interactions with each other, and their roles in TGF-beta-mediated growth inhibitory effects are not well understood. To address these questions, we have utilized a human breast cancer cell line MCF10CA1h and demonstrate that p38 MAP kinase and Rho/ROCK pathways together with Smad2 and Smad3 are necessary for TGF-beta-mediated growth inhibition of this cell line. We show that Smad2/3 are indispensable for TGF-beta-mediated growth inhibition, and that both p38 and Rho/ROCK pathways affect the linker region phosphorylation of Smad2/3. Further, by using Smad3 mutated at the putative phosphorylation sites in the linker region, we demonstrate that phosphorylation at Ser203 and Ser207 residues is required for the full transactivation potential of Smad3, and that these residues are targets of the p38 and Rho/ROCK pathways. We demonstrate that activation of the p38 MAP kinase pathway is necessary for the full transcriptional activation potential of Smad2/Smad3 by TGF-beta, whereas activity of Rho/ROCK is necessary for both down-regulation of c-Myc protein and up-regulation of p21waf1 protein, directly interfering with p21waf1 transcription. Our results not only implicate Rho/ROCK and p38 MAPK pathways as necessary for TGF-beta-mediated growth inhibition, but also demonstrate their individual contributions and the basis for their cooperation with each other. JF - The Journal of biological chemistry AU - Kamaraju, Anil K AU - Roberts, Anita B AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892-5055, USA. Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 SP - 1024 EP - 1036 VL - 280 IS - 2 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Intracellular Signaling Peptides and Proteins KW - Oncogene Protein p55(v-myc) KW - Retinoblastoma Protein KW - SMAD2 protein, human KW - SMAD3 protein, human KW - Smad2 Protein KW - Smad3 Protein KW - Trans-Activators KW - Transforming Growth Factor beta KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - rho-Associated Kinases KW - p38 Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Index Medicus KW - Cell Proliferation -- drug effects KW - Oncogene Protein p55(v-myc) -- metabolism KW - Humans KW - Retinoblastoma Protein -- metabolism KW - Cell Line, Tumor KW - Down-Regulation -- drug effects KW - Phosphorylation -- drug effects KW - Transforming Growth Factor beta -- pharmacology KW - Trans-Activators -- metabolism KW - MAP Kinase Signaling System -- drug effects KW - Protein-Serine-Threonine Kinases -- metabolism KW - Breast Neoplasms -- pathology KW - Breast Neoplasms -- metabolism KW - Breast Neoplasms -- enzymology KW - p38 Mitogen-Activated Protein Kinases -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67367290?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Role+of+Rho%2FROCK+and+p38+MAP+kinase+pathways+in+transforming+growth+factor-beta-mediated+Smad-dependent+growth+inhibition+of+human+breast+carcinoma+cells+in+vivo.&rft.au=Kamaraju%2C+Anil+K%3BRoberts%2C+Anita+B&rft.aulast=Kamaraju&rft.aufirst=Anil&rft.date=2005-01-14&rft.volume=280&rft.issue=2&rft.spage=1024&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 - 2005-02-25 N1 - Date created - 2005-01-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Experimental project of assertive community treatment in Japan (ACT-J): The interim report of the pilot study AN - 40008797; 3903484 AU - Ito, J Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/40008797?accountid=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=Experimental+project+of+assertive+community+treatment+in+Japan+%28ACT-J%29%3A+The+interim+report+of+the+pilot+study&rft.au=Ito%2C+J&rft.aulast=Ito&rft.aufirst=J&rft.date=2005-01-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Congress Corporation, Kosai Kaikan Bldg., 6th Floor, 5-1 Kojimachi, Chiyoda-ku, Tokyo 102-8481, Japan; phone: 81 (03) 5216-5551; fax: 81 (03) 5216-5552; URL: www.congre.co.jp N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Synaptic localization of N-type Ca super(2)+-channels depends on the interaction with light chains of microtubule-associated proteins AN - 39984904; 3908295 AU - Leenders, AGM AU - Sheng, Z-H Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39984904?accountid=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=Synaptic+localization+of+N-type+Ca+super%282%29%2B-channels+depends+on+the+interaction+with+light+chains+of+microtubule-associated+proteins&rft.au=Leenders%2C+AGM%3BSheng%2C+Z-H&rft.aulast=Leenders&rft.aufirst=AGM&rft.date=2005-01-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Elsevier, Neuropharmacology Conf. Secr., Bregor, Winter Lane, West Hanney, Nr Wantage, Oxon OX12 OLF, Great Britain; phone: 44 (01235) 868 811; fax: 44 (01235) 868 811 N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - COMT: Evidence that VAL158MET is the functional variant affecting risk for schizophrenia AN - 39980464; 3902060 AU - Egan, M F Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39980464?accountid=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=COMT%3A+Evidence+that+VAL158MET+is+the+functional+variant+affecting+risk+for+schizophrenia&rft.au=Egan%2C+M+F&rft.aulast=Egan&rft.aufirst=M&rft.date=2005-01-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: St. James Hosp., Trinity Ctr. f. Health Sciences, James Street, Dublin 8, Ireland; URL: www.wcpg2004.ie N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Dysbindin (DTNBP1,6p22.3) is associated with childhood onset psychosis and endophenotypes measured by the premorbid adjustment scale (PAS) AN - 39977559; 3902772 AU - Gornick, M C Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39977559?accountid=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=Dysbindin+%28DTNBP1%2C6p22.3%29+is+associated+with+childhood+onset+psychosis+and+endophenotypes+measured+by+the+premorbid+adjustment+scale+%28PAS%29&rft.au=Gornick%2C+M+C&rft.aulast=Gornick&rft.aufirst=M&rft.date=2005-01-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: St. James Hosp., Trinity Ctr. f. Health Sciences, James Street, Dublin 8, Ireland; URL: www.wcpg2004.ie N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Challenges in clinical islet transplantation AN - 39974677; 3901614 AU - Harlan, D Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39974677?accountid=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=Challenges+in+clinical+islet+transplantation&rft.au=Harlan%2C+D&rft.aulast=Harlan&rft.aufirst=D&rft.date=2005-01-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: City of Hope Natl. Medical Ctr., Diabetes & Genetic Research Ctr., 1500 E Duarte Road, Duarte, CA 91010, USA; URL: www.levinesymposium.coh.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Vector specificity, pathogenicity, and genomic comparisons of tick-borne spirochetes AN - 39957005; 3908910 AU - Schwan, T G Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39957005?accountid=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=Vector+specificity%2C+pathogenicity%2C+and+genomic+comparisons+of+tick-borne+spirochetes&rft.au=Schwan%2C+T+G&rft.aulast=Schwan&rft.aufirst=T&rft.date=2005-01-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Entomological Society of America, 9301 Annapolis Rd., Lanham, MD 20706, USA; URL: www.entsoc.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Interactions of Yersinia pestis with its flea vector that lead to the transmission of plague AN - 39954928; 3904825 AU - Hinnebusch, B J Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39954928?accountid=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=Interactions+of+Yersinia+pestis+with+its+flea+vector+that+lead+to+the+transmission+of+plague&rft.au=Hinnebusch%2C+B+J&rft.aulast=Hinnebusch&rft.aufirst=B&rft.date=2005-01-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: Entomological Society of America, 9301 Annapolis Rd., Lanham, MD 20706, USA; URL: www.entsoc.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - NIDDK: Basic and clinical islet transplantation programs AN - 39904346; 3906096 AU - Eggerman, T Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39904346?accountid=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=NIDDK%3A+Basic+and+clinical+islet+transplantation+programs&rft.au=Eggerman%2C+T&rft.aulast=Eggerman&rft.aufirst=T&rft.date=2005-01-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: City of Hope Natl. Medical Ctr., Diabetes & Genetic Research Ctr., 1500 E Duarte Road, Duarte, CA 91010, USA; URL: www.levinesymposium.coh.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Role for genomic imprinting in human sexual orientation AN - 39899632; 3907529 AU - Bocklandt, S Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39899632?accountid=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+for+genomic+imprinting+in+human+sexual+orientation&rft.au=Bocklandt%2C+S&rft.aulast=Bocklandt&rft.aufirst=S&rft.date=2005-01-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: St. James Hosp., Trinity Ctr. f. Health Sciences, James Street, Dublin 8, Ireland; URL: www.wcpg2004.ie N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - NIAID: Allergy, immunology, & transplantation programs AN - 39889954; 3906094 AU - Rotrosen, D Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39889954?accountid=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=NIAID%3A+Allergy%2C+immunology%2C+%26amp%3B+transplantation+programs&rft.au=Rotrosen%2C+D&rft.aulast=Rotrosen&rft.aufirst=D&rft.date=2005-01-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: City of Hope Natl. Medical Ctr., Diabetes & Genetic Research Ctr., 1500 E Duarte Road, Duarte, CA 91010, USA; URL: www.levinesymposium.coh.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - BDNF and mood disorders: A novel functional promoter polymorphism and VAL66MET are associated with anxiety but have opposing effects AN - 39852186; 3901288 AU - Lipsky, R H Y1 - 2005/01/14/ PY - 2005 DA - 2005 Jan 14 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39852186?accountid=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=BDNF+and+mood+disorders%3A+A+novel+functional+promoter+polymorphism+and+VAL66MET+are+associated+with+anxiety+but+have+opposing+effects&rft.au=Lipsky%2C+R+H&rft.aulast=Lipsky&rft.aufirst=R&rft.date=2005-01-14&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - SuppNotes - Availability: St. James Hosp., Trinity Ctr. f. Health Sciences, James Street, Dublin 8, Ireland; URL: www.wcpg2004.ie N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Beta-glucuronidase-cleavable prodrugs of O6-benzylguanine and O6-benzyl-2'-deoxyguanosine. AN - 67341134; 15634019 AB - Glucuronic acid linked prodrugs of O(6)-benzylguanine and O(6)-benzyl-2'-deoxyguanosine were synthesized. The prodrugs were found to be quite stable at physiological pH and were more than 200-fold less active as inactivators of O(6)-alkylguanine-DNA alkyltransferase (alkyltransferase) than either O(6)-benzylguanine or O(6)-benzyl-2'-deoxyguanosine. Beta-glucuronidase from both Escherichia coli and bovine liver cleaved the prodrugs efficiently to release O(6)-benzylguanine and O(6)-benzyl-2'-deoxyguanosine, respectively. In combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), the prodrugs were not effective adjuvants for HT29 cell killing. However, as expected, incubation of these prodrugs with beta-glucuronidase in the culture medium led to much more efficient cell killing by BCNU as a result of the liberation of the more potent inactivators, O(6)-benzylguanine and O(6)-benzyl-2'-deoxyguanosine. These prodrugs may be useful for prodrug monotherapy of necrotic tumors that liberate beta-glucuronidase or for antibody-directed enzyme prodrug therapy with antibodies that can deliver beta-glucuronidase to target tumor cells. JF - Journal of medicinal chemistry AU - Wei, Guangping AU - Loktionova, Natalia A AU - Pegg, Anthony E AU - Moschel, Robert C AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, PO Box B, Bldg. 538, Frederick, Maryland 21702, USA. Y1 - 2005/01/13/ PY - 2005 DA - 2005 Jan 13 SP - 256 EP - 261 VL - 48 IS - 1 SN - 0022-2623, 0022-2623 KW - Antineoplastic Agents KW - 0 KW - Prodrugs KW - O(6)-benzylguanine KW - 01KC87F8FE KW - O(6)-benzyl-2'-deoxyguanosine KW - 129732-90-7 KW - Guanine KW - 5Z93L87A1R KW - Alkyl and Aryl Transferases KW - EC 2.5.- KW - Glucuronidase KW - EC 3.2.1.31 KW - Deoxyguanosine KW - G9481N71RO KW - Carmustine KW - U68WG3173Y KW - Index Medicus KW - Animals KW - Drug Stability KW - Liver -- enzymology KW - Alkyl and Aryl Transferases -- drug effects KW - Humans KW - Antineoplastic Agents -- metabolism KW - HT29 Cells -- drug effects KW - Alkyl and Aryl Transferases -- antagonists & inhibitors KW - Escherichia coli -- enzymology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Cell Death -- drug effects KW - Hydrolysis KW - Cattle KW - Biochemistry -- methods KW - Kinetics KW - Enzyme Activation -- drug effects KW - Carmustine -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Deoxyguanosine -- metabolism KW - Prodrugs -- pharmacology KW - Glucuronidase -- metabolism KW - Guanine -- chemical synthesis KW - Guanine -- analogs & derivatives KW - Deoxyguanosine -- pharmacology KW - Deoxyguanosine -- chemical synthesis KW - Prodrugs -- metabolism KW - Guanine -- pharmacology KW - Guanine -- metabolism KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67341134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Beta-glucuronidase-cleavable+prodrugs+of+O6-benzylguanine+and+O6-benzyl-2%27-deoxyguanosine.&rft.au=Wei%2C+Guangping%3BLoktionova%2C+Natalia+A%3BPegg%2C+Anthony+E%3BMoschel%2C+Robert+C&rft.aulast=Wei&rft.aufirst=Guangping&rft.date=2005-01-13&rft.volume=48&rft.issue=1&rft.spage=256&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 - 2005-02-17 N1 - Date created - 2005-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pax2 expression occurs in renal medullary epithelial cells in vivo and in cell culture, is osmoregulated, and promotes osmotic tolerance AN - 20217264; 6175442 AB - Pax2 is a transcription factor that is crucial for kidney development, and it is also expressed in the normal adult kidney, where its physiological function is unknown. In the present study, we find by cDNA microarray analysis that Pax2 expression in second-passage mouse inner-medullary epithelial cells is increased by a high NaCl concentration, which is significant because NaCl levels are normally high in the inner medulla in vivo, and varies with urinary concentration. Furthermore, a high NaCl concentration increases Pax2 mRNA and protein expression in mouse inner medullary collecting duct (mIMCD3) cells, and its transcriptional activity. Pax2 mRNA and protein expression is high in normal adult mouse renal inner medulla but much lower in renal cortex. Pax2 protein is present in collecting duct cells in both renal medulla and cortex and in thin descending limbs of Henle's loop in inner medulla. Treating Brattleboro rats with desamino-Cys-1,D-Arg-8 vasopressin, which increases inner-medullary NaCl concentration, causes a 4-fold increase in inner-medullary Pax2 protein. Treatment with furosemide, which decreases inner-medullary NaCl, reduces inner- medullary Pax2 mRNA and protein. Pax2-specific short interfering RNA increases high NaCl concentration-induced activation of caspase-3 and apoptotic bodies in mIMCD3 cells. We thus conclude that (i) Pax2 is expressed in normal renal medulla, (ii) its expression is regulated there by the normally high and variable NaCl concentration, and (iii) it protects renal medullary cells from high NaCl concentration-induced apoptosis. JF - Proceedings of the National Academy of Sciences, USA AU - Cai, Qi AU - Dmitrieva, Natalia I AU - Ferraris, Joan D AU - Brooks, Heddwen L AU - van balkom, Bas WM AU - Burg, Maurice AD - Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD Y1 - 2005/01/11/ PY - 2005 DA - 2005 Jan 11 SP - 503 EP - 508 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 102 IS - 2 SN - 0027-8424, 0027-8424 KW - Biotechnology and Bioengineering Abstracts KW - Pax2 protein KW - Epithelial cells KW - Apoptosis KW - renal cortex KW - Cell culture KW - furosemide KW - DNA microarrays KW - Gene expression KW - Limbs KW - Collecting duct KW - siRNA KW - Vasopressin KW - Transcription factors KW - Kidney KW - Caspase-3 KW - Sodium chloride KW - W 30945:Fermentation & Cell Culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20217264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pax2+expression+occurs+in+renal+medullary+epithelial+cells+in+vivo+and+in+cell+culture%2C+is+osmoregulated%2C+and+promotes+osmotic+tolerance&rft.au=Cai%2C+Qi%3BDmitrieva%2C+Natalia+I%3BFerraris%2C+Joan+D%3BBrooks%2C+Heddwen+L%3Bvan+balkom%2C+Bas+WM%3BBurg%2C+Maurice&rft.aulast=Cai&rft.aufirst=Qi&rft.date=2005-01-11&rft.volume=102&rft.issue=2&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-09-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Pax2 protein; Epithelial cells; Apoptosis; renal cortex; Cell culture; DNA microarrays; furosemide; Gene expression; Collecting duct; Limbs; Vasopressin; siRNA; Transcription factors; Caspase-3; Kidney; Sodium chloride ER - TY - JOUR T1 - Prevention of hormone-related cancers: prostate cancer. AN - 67348257; 15637399 AB - Androgens are known to play an important role in normal prostate development, benign prostatic hyperplasia, established prostate cancer, and in prostate carcinogenesis. However, despite convincing experimental and clinical evidence, the epidemiologic data correlating sex steroid levels with disease risk is inconsistent. More recent work has focused on studies of polymorphisms in germ-line DNA in an effort to develop polygenic models of prostate cancer susceptibility and prognosis. Such models have the potential to aid in the selection of men for specific chemopreventive interventions and to help determine which men with localized prostate cancer are most likely to benefit from aggressive therapy. In this review, we will provide a brief summary of androgen metabolic pathways followed by an assessment of the epidemiology literature addressing the relationship between androgens and prostate cancer. Finally, we will address the two major questions that have arisen in response to the recently published results from the Prostate Cancer Prevention Trial: Who are the best candidates for finasteride chemoprevention, and what are the clinical implications of the high prevalence of prostate cancer that was detected in men with prostate-specific antigen levels in the so-called "normal" range? JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Parnes, Howard L AU - Thompson, Ian M AU - Ford, Leslie G AD - National Cancer Institute, 6130 Executive Blvd, Room 2046, Bethesda, MD 20892, USA. Y1 - 2005/01/10/ PY - 2005 DA - 2005 Jan 10 SP - 368 EP - 377 VL - 23 IS - 2 SN - 0732-183X, 0732-183X KW - Androgens KW - 0 KW - Antineoplastic Agents, Hormonal KW - Enzyme Inhibitors KW - Finasteride KW - 57GNO57U7G KW - Prostate-Specific Antigen KW - EC 3.4.21.77 KW - Index Medicus KW - Enzyme Inhibitors -- therapeutic use KW - Polymorphism, Genetic KW - Risk Factors KW - Models, Genetic KW - Humans KW - Prostate-Specific Antigen -- blood KW - Finasteride -- therapeutic use KW - Clinical Trials as Topic KW - Genetic Predisposition to Disease KW - Antineoplastic Agents, Hormonal -- therapeutic use KW - Male KW - Prostatic Neoplasms -- metabolism KW - Prostatic Neoplasms -- epidemiology KW - Androgens -- physiology KW - Prostatic Neoplasms -- prevention & control KW - Androgens -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67348257?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Prevention+of+hormone-related+cancers%3A+prostate+cancer.&rft.au=Parnes%2C+Howard+L%3BThompson%2C+Ian+M%3BFord%2C+Leslie+G&rft.aulast=Parnes&rft.aufirst=Howard&rft.date=2005-01-10&rft.volume=23&rft.issue=2&rft.spage=368&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 - 2005-02-01 N1 - Date created - 2005-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nutritional interventions in cancer prevention. AN - 67348055; 15637396 AB - The first generation of phase III nutritional intervention studies to prevent cancer has been completed. Nearly 150,000 total participants were studied in nine different interventions using randomized, double-blind, placebo-controlled designs that tested whether vitamins and/or minerals, given singly or in combination, could prevent total or site-specific cancer. The primary agents tested include beta-carotene, alpha-tocopherol, selenium, and retinol. This review summarizes the findings from the first generation of human experimental studies that tested micronutrients in the prevention of cancer, discusses lessons learned from these studies, identifies the most promising leads, and describes future prospects in nutritional intervention research. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Taylor, Philip R AU - Greenwald, Peter AD - National Cancer Institute, 6116 Executive Blvd, Rm 705, Bethesda, MD 20892-8314, USA. ptaylor@mail.nih.gov Y1 - 2005/01/10/ PY - 2005 DA - 2005 Jan 10 SP - 333 EP - 345 VL - 23 IS - 2 SN - 0732-183X, 0732-183X KW - Vitamins KW - 0 KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Clinical Trials, Phase II as Topic KW - Double-Blind Method KW - Humans KW - Aged KW - Research Design KW - Nutritional Requirements KW - Adult KW - Incidence KW - Forecasting KW - Middle Aged KW - Maximum Tolerated Dose KW - Time Factors KW - Vitamins -- pharmacology KW - Neoplasms -- epidemiology KW - Neoplasms -- prevention & control KW - Dietary Supplements UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67348055?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Nutritional+interventions+in+cancer+prevention.&rft.au=Taylor%2C+Philip+R%3BGreenwald%2C+Peter&rft.aulast=Taylor&rft.aufirst=Philip&rft.date=2005-01-10&rft.volume=23&rft.issue=2&rft.spage=333&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 - 2005-02-01 N1 - Date created - 2005-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Colorectal cancer prevention. AN - 67346653; 15637400 AB - Colorectal cancer is the second leading cause of mortality in the United States. In the United States, the cumulative lifetime risk of developing colorectal cancer for both men and women is 6%. Despite advances in the management of this disease, the 5-year survival rate in the United States in only 62%. Because only 38% of patients are diagnosed when the cancers are localized to the bowel wall, it is likely that widespread implementation of screening could significantly improve the outcome. Colorectal cancer screening is cost effective, irrespective of the methods used. In addition to currently available methods (fecal occult blood, flexible sigmoidoscopy, colonoscopy, and double contrast barium enema), computed tomographic colonography (virtual colonoscopy) and stool-based molecular screening are under development. Four classes of chemopreventive compounds have demonstrated efficacy in reducing recurrent colorectal adenomas and/or cancer in randomized, controlled trials. They are selenium, calcium carbonate, hormone replacement therapy, and nonsteroidal anti-inflammatory drugs. The mechanisms of action of nonsteroidal anti-inflammatory drugs include inhibition of the cyclooxygenase system as well as cyclooxygenase-independent effects. Considerable effort is being expended to define chemopreventive activity, optimal dose, administration schedule, and toxicity for the coxibs in adenoma recurrence prevention trials. The threshold for tolerating toxicities is very low in asymptomatic individuals at minimally increased risk for colorectal neoplasia. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Hawk, Ernest T AU - Levin, Bernard AD - GI and Other Cancers Research Group, National Cancer Institute, 6130 Executive Boulevard, Suite 2141, Bethesda, MD 20892-7322, USA. eh51p@nih.gov Y1 - 2005/01/10/ PY - 2005 DA - 2005 Jan 10 SP - 378 EP - 391 VL - 23 IS - 2 SN - 0732-183X, 0732-183X KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cyclooxygenase Inhibitors KW - Aspirin KW - R16CO5Y76E KW - Index Medicus KW - Precancerous Conditions -- therapy KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Humans KW - Clinical Trials as Topic KW - Patient Selection KW - Adenomatous Polyps -- complications KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Risk KW - Colonic Polyps -- diagnosis KW - Adenomatous Polyps -- diagnosis KW - Aspirin -- therapeutic use KW - Precancerous Conditions -- diagnosis KW - Forecasting KW - Female KW - Male KW - Colorectal Neoplasms -- diagnosis KW - Colorectal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67346653?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Colorectal+cancer+prevention.&rft.au=Hawk%2C+Ernest+T%3BLevin%2C+Bernard&rft.aulast=Hawk&rft.aufirst=Ernest&rft.date=2005-01-10&rft.volume=23&rft.issue=2&rft.spage=378&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 - 2005-02-01 N1 - Date created - 2005-01-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention of hormone-related cancers: breast cancer. AN - 67345765; 15637398 AB - Carcinogenesis in the breast is a hormonally dependent process. Evidence implicating estrogen as a key breast carcinogen comes from various lines of investigation. Traditional epidemiologic studies demonstrate associations between estrogen exposure, both exogenous and endogenous, and increased breast cancer risk. Ongoing genetic epidemiologic studies also show associations between specific polymorphisms in estrogen-metabolizing genes and risk, albeit inconsistently. The application of these findings to the treatment and, more recently, the prevention of breast cancer has led to the development of agents that either (1) inhibit estrogen action at the estrogen receptor (selective estrogen receptor modulators (SERMs]); or (2) inhibit estrogen-synthesizing enzymes, thereby abrogating synthesis of this hormone (aromatase inhibitors). Large phase III trials have evaluated the ability of such agents to reduce the incidence of breast cancer in women at increased risk of the disease. The National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1: Breast Cancer Prevention Trial (BCPT) demonstrated the superiority of the SERM tamoxifen to placebo in reducing breast cancer risk, leading to the Food and Drug Administration approval of tamoxifen for risk reduction. The implementation of tamoxifen for this indication has not become widespread in clinical practice, however, for a variety of reasons that we discuss. Results from the NSABP Study of Tamoxifen and Raloxifene, which compares the risk-reducing efficacy as well as toxicity of these two SERMs in a similar high-risk population, will be available in the near future. Based on promising data involving reduction of contralateral breast cancer risk in adjuvant studies, several aromatase inhibitors, including letrozole, anastrozole, and exemestane, are being incorporated into trials evaluating their efficacy as preventive agents in women at increased risk. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Dunn, Barbara K AU - Wickerham, D Lawrence AU - Ford, Leslie G AD - National Cancer Institute, 6130 Executive Blvd, Room 2046, Bethesda, MD 20892, USA. Y1 - 2005/01/10/ PY - 2005 DA - 2005 Jan 10 SP - 357 EP - 367 VL - 23 IS - 2 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Hormonal KW - 0 KW - Aromatase Inhibitors KW - Selective Estrogen Receptor Modulators KW - Tamoxifen KW - 094ZI81Y45 KW - Raloxifene Hydrochloride KW - 4F86W47BR6 KW - Index Medicus KW - Randomized Controlled Trials as Topic KW - Clinical Trials, Phase II as Topic KW - Tamoxifen -- therapeutic use KW - Humans KW - Raloxifene Hydrochloride -- therapeutic use KW - Antineoplastic Agents, Hormonal -- therapeutic use KW - Female KW - Selective Estrogen Receptor Modulators -- therapeutic use KW - Breast Neoplasms -- prevention & control KW - Neoplasms, Hormone-Dependent -- prevention & control KW - Aromatase Inhibitors -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67345765?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Prevention+of+hormone-related+cancers%3A+breast+cancer.&rft.au=Dunn%2C+Barbara+K%3BWickerham%2C+D+Lawrence%3BFord%2C+Leslie+G&rft.aulast=Dunn&rft.aufirst=Barbara&rft.date=2005-01-10&rft.volume=23&rft.issue=2&rft.spage=357&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 - 2005-02-01 N1 - Date created - 2005-01-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 2005 Jul 1;23(19):4469-70 [15994163] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1. AN - 67327919; 15603755 AB - Cytochromes P450 are responsible for metabolism of most xenobiotics and are required for the efficient elimination of foreign chemicals from the body. Paradoxically, these enzymes also metabolically activate biologically inert compounds to electrophilic derivatives that can cause toxicity, cell death and sometimes cellular transformation resulting in cancer. To establish the role of these enzymes in toxicity and carcinogenicity in vivo, gene knockout mice have been developed. To illustrate the role of P450s in toxicity, CYP2E1-null mice were employed with the commonly used analgesic drug acetaminophen. CYP2E1 is the rate-limiting enzyme that initiates the cascade of events leading to acetaminophen hepatotoxicity; in the absence of this P450, toxicity will only be apparent at high concentrations. Other enzymes and nuclear receptors are also involved in activation or inactivating chemicals. CYP2E1 is induced by alcohol and the primary P450 that carries out ethanol oxidation that can lead to the production of activated oxygen species and oxidative stress that elevate ERK1/2 phosphorylation through EGRF/c-Raf signaling. Paradoxically, activation of this pathway inhibits apoptotic cell death stimulated by reactive oxygen generating chemicals but accelerates necrotic cell death produced by polyunsaturated fatty acids. CYP2E1 is thought to contribute to liver pathologies that result from alcoholic liver disease and non-alcoholic steatohepatitis. JF - Mutation research AU - Gonzalez, Frank J AD - Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA. fjgonz@helix.nih.gov Y1 - 2005/01/06/ PY - 2005 DA - 2005 Jan 06 SP - 101 EP - 110 VL - 569 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Reactive Oxygen Species KW - 0 KW - Xenobiotics KW - Acetaminophen KW - 362O9ITL9D KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Xenobiotics -- pharmacokinetics KW - Acetaminophen -- pharmacokinetics KW - Inactivation, Metabolic KW - Humans KW - Apoptosis -- drug effects KW - Xenobiotics -- toxicity KW - Chemical and Drug Induced Liver Injury -- metabolism KW - Chemical and Drug Induced Liver Injury -- enzymology KW - Acetaminophen -- toxicity KW - Drug-Related Side Effects and Adverse Reactions -- enzymology KW - Oxidative Stress KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Drug-Related Side Effects and Adverse Reactions -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67327919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+cytochromes+P450+in+chemical+toxicity+and+oxidative+stress%3A+studies+with+CYP2E1.&rft.au=Gonzalez%2C+Frank+J&rft.aulast=Gonzalez&rft.aufirst=Frank&rft.date=2005-01-06&rft.volume=569&rft.issue=1-2&rft.spage=101&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 - 2005-03-03 N1 - Date created - 2004-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An unusual signal peptide facilitates late steps in the biogenesis of a bacterial autotransporter AN - 17863068; 6174618 AB - Bacterial autotransporters are proteins that use a C-terminal porin-like domain to facilitate the transport of an upstream "passenger domain" across the outer membrane. Although autotransporters are translocated across the inner membrane (IM) via the Sec pathway, some of them contain exceptionally long signal peptides distinguished by a unique N-terminal sequence motif. In this study, we used the Escherichia coli O157:H7 autotransporter EspP as a model protein to investigate the function of the unusual signal peptides. We found that removal of the N-terminal motif or replacement of the EspP signal peptide did not affect translocation of the protein across the IM. Remarkably, modification of the signal peptide caused EspP to misfold in the periplasm and blocked transport of the passenger domain across the outer membrane. Further analysis suggested that the EspP signal peptide transits slowly through the Sec machinery. Based on these results, we propose that the unusual signal peptides not only function as targeting signals, but also prevent misfolding of the passenger domain in the periplasm by transiently tethering it to the IM. JF - Proceedings of the National Academy of Sciences, USA AU - Szabady, Rose L AU - Peterson, Janine H AU - Skillman, Kristen M AU - Bernstein, Harris D AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD Y1 - 2005/01/04/ PY - 2005 DA - 2005 Jan 04 SP - 221 EP - 226 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 102 IS - 1 SN - 0027-8424, 0027-8424 KW - EspP protein KW - Microbiology Abstracts B: Bacteriology KW - Protein folding KW - Inner membranes KW - Outer membranes KW - Signal peptides KW - Escherichia coli KW - Translocation KW - periplasm KW - Models KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17863068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=An+unusual+signal+peptide+facilitates+late+steps+in+the+biogenesis+of+a+bacterial+autotransporter&rft.au=Szabady%2C+Rose+L%3BPeterson%2C+Janine+H%3BSkillman%2C+Kristen+M%3BBernstein%2C+Harris+D&rft.aulast=Szabady&rft.aufirst=Rose&rft.date=2005-01-04&rft.volume=102&rft.issue=1&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Signal peptides; Outer membranes; periplasm; Translocation; Protein folding; Models; Inner membranes ER - TY - JOUR T1 - Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. AN - 67343657; 15630141 AB - Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor gamma chain (gamma(c)), which is mutated in humans with X-linked severe combined immunodeficiency. We now report that IL-21 synergistically acts with IL-15 to potently promote the proliferation of both memory (CD44high) and naive (CD44low) phenotype CD8+ T cells and augment interferon-gamma production in vitro. IL-21 also cooperated, albeit more weakly, with IL-7, but not with IL-2. Correspondingly, the expansion and cytotoxicity of CD8+ T cells were impaired in IL-21R-/- mice. Moreover, in vivo administration of IL-21 in combination with IL-15 boosted antigen-specific CD8+ T cell numbers and resulted in a cooperative effect on tumor regression, with apparent cures of large, established B16 melanomas. Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15. JF - The Journal of experimental medicine AU - Zeng, Rong AU - Spolski, Rosanne AU - Finkelstein, Steven E AU - Oh, SangKon AU - Kovanen, Panu E AU - Hinrichs, Christian S AU - Pise-Masison, Cynthia A AU - Radonovich, Michael F AU - Brady, John N AU - Restifo, Nicholas P AU - Berzofsky, Jay A AU - Leonard, Warren J AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2005/01/03/ PY - 2005 DA - 2005 Jan 03 SP - 139 EP - 148 VL - 201 IS - 1 SN - 0022-1007, 0022-1007 KW - 5-(6)-carboxyfluorescein diacetate succinimidyl ester KW - 0 KW - Fluoresceins KW - HIV Envelope Protein gp160 KW - Interleukin-15 KW - Interleukin-7 KW - Interleukins KW - Succinimides KW - interleukin-21 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Cell Proliferation -- drug effects KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Mice KW - Mice, Inbred BALB C KW - Immunologic Memory -- immunology KW - Interleukin-7 -- metabolism KW - Mice, Inbred C57BL KW - Immunotherapy, Adoptive KW - Interferon-gamma -- metabolism KW - Cytotoxicity Tests, Immunologic KW - Flow Cytometry KW - Drug Synergism KW - Interleukins -- pharmacology KW - CD8-Positive T-Lymphocytes -- drug effects KW - CD8-Positive T-Lymphocytes -- immunology KW - Interleukins -- therapeutic use KW - Interleukins -- metabolism KW - Interleukin-15 -- therapeutic use KW - Interleukin-15 -- pharmacology KW - Interleukin-15 -- metabolism KW - Melanoma, Experimental -- therapy KW - Melanoma, Experimental -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67343657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Synergy+of+IL-21+and+IL-15+in+regulating+CD8%2B+T+cell+expansion+and+function.&rft.au=Zeng%2C+Rong%3BSpolski%2C+Rosanne%3BFinkelstein%2C+Steven+E%3BOh%2C+SangKon%3BKovanen%2C+Panu+E%3BHinrichs%2C+Christian+S%3BPise-Masison%2C+Cynthia+A%3BRadonovich%2C+Michael+F%3BBrady%2C+John+N%3BRestifo%2C+Nicholas+P%3BBerzofsky%2C+Jay+A%3BLeonard%2C+Warren+J&rft.aulast=Zeng&rft.aufirst=Rong&rft.date=2005-01-03&rft.volume=201&rft.issue=1&rft.spage=139&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 - 2005-03-28 N1 - Date created - 2005-01-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 2000 Nov 2;408(6808):57-63 [11081504] Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 [9843981] Nat Immunol. 2000 Nov;1(5):426-32 [11062503] Cytokine Growth Factor Rev. 2002 Apr;13(2):169-83 [11900992] Nat Rev Immunol. 2001 Dec;1(3):200-8 [11905829] Immunity. 2002 Apr;16(4):559-69 [11970879] Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8832-7 [12084927] Nat Rev Immunol. 2002 Aug;2(8):547-56 [12154374] J Exp Med. 2002 Oct 7;196(7):935-46 [12370255] Science. 2002 Oct 25;298(5594):850-4 [12242449] Cytokine Growth Factor Rev. 2002 Dec;13(6):429-39 [12401478] Science. 2002 Nov 22;298(5598):1630-4 [12446913] J Immunol. 2003 Jan 1;170(1):210-7 [12496402] Nat Med. 2003 Mar;9(3):279-86 [12579196] Cancer Gene Ther. 2003 Mar;10(3):187-92 [12637939] Nat Rev Immunol. 2003 Apr;3(4):269-79 [12669018] J Immunol. 2003 May 15;170(10):5018-26 [12734346] J Immunol. 2003 Jul 15;171(2):608-15 [12847225] J Exp Med. 2003 Aug 18;198(4):569-80 [12925674] Mol Ther. 2003 Oct;8(4):552-8 [14529827] Nat Immunol. 2003 Dec;4(12):1191-8 [14625547] Cancer Res. 2003 Dec 15;63(24):9016-22 [14695220] Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1969-74 [14762166] Cell. 2004 Apr 16;117(2):265-77 [15084263] Science. 2000 Apr 28;288(5466):675-8 [10784451] Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11439-44 [11016959] J Leukoc Biol. 2004 Aug;76(2):333-7 [15155774] Proc Natl Acad Sci U S A. 1988 May;85(9):3105-9 [2452443] J Virol. 1990 May;64(5):2448-51 [2182912] Cell. 1993 Apr 9;73(1):147-57 [8462096] J Immunol. 1995 Feb 15;154(4):1973-86 [7530749] J Exp Med. 1997 Jan 20;185(2):189-95 [9016868] Immunity. 1998 May;8(5):591-9 [9620680] Immunity. 2001 Feb;14(2):105-10 [11239443] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expressive Vocabulary in Language Learners from Two Ecological Settings in Three Language Communities AN - 85633844; 200605027 AB - This study compared multiple characteristics of girls' & boys' vocabulary in 6 different linguistic communities - 1 urban & 1 rural setting in each of 3 countries. Two hundred fifty-two mothers in Argentina, Italy, & the United States completed vocabulary checklists for their 20-month-old children. Individual variability was substantial within each linguistic community. Minimal cross-linguistic differences were found in children's vocabulary size; however, differences among languages in the composition of children's vocabularies appeared possibly related to cultural valuing of different categories of words. Ecological setting differences within cultures appeared in children's vocabulary size, even when the composition of children's vocabularies was examined: Children living in urban areas were reported by their mothers to say significantly more words than children living in rural areas, particularly for Argentine & U.S. children. Girls had consistently larger vocabularies than boys. These findings are discussed in terms of contextual & child factors that together influence first language learning. 5 Tables, 65 References. Adapted from the source document JF - Infancy AU - Bornstein, Marc H AU - Cote, Linda R AD - National Instit Child Health & Human Development, Bethesda, MD Marc_H_Bornstein@nih.gov Y1 - 2005///0, PY - 2005 DA - 0, 2005 SP - 299 EP - 316 VL - 7 IS - 3 SN - 1525-0008, 1525-0008 KW - Italy (39100) KW - Sex Differences (77850) KW - Lexicon (47150) KW - Learning Environment (45880) KW - Argentina (03950) KW - Urban versus Rural Areas (92980) KW - Language Culture Relationship (42150) KW - Language Acquisition (41600) KW - Expressive Function of Language (23500) KW - United States of America (92750) KW - Speech Communities (82410) KW - Children (11850) KW - article KW - 4015: psycholinguistics; child language acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85633844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infancy&rft.atitle=Expressive+Vocabulary+in+Language+Learners+from+Two+Ecological+Settings+in+Three+Language+Communities&rft.au=Bornstein%2C+Marc+H%3BCote%2C+Linda+R&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=2005-01-01&rft.volume=7&rft.issue=3&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Infancy&rft.issn=15250008&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2006-05-01 N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Expressive Function of Language (23500); Lexicon (47150); Speech Communities (82410); Children (11850); Language Acquisition (41600); Sex Differences (77850); Urban versus Rural Areas (92980); Language Culture Relationship (42150); Learning Environment (45880); Argentina (03950); Italy (39100); United States of America (92750) ER - TY - JOUR T1 - Treatment with medications affecting dopaminergic and serotonergic mechanisms: effects on fluency and anxiety in persons who stutter. AN - 85395052; pmid-16246409 AB - Medications with dopamine antagonist properties, such as haloperidol, and those with serotonin reuptake inhibitor properties, such as clomipramine, have been shown to improve fluency. To examine the degree to which each of these two pharmacological mechanisms might independently affect fluency, a selective serotonin reuptake inhibitor, paroxetine, and a selective dopamine (D-2) antagonist, pimozide, were evaluated. Both types of medications also affect mood and anxiety, factors that could influence fluency levels. Therefore, we also evaluated the medications' effects on generalized and speech-related anxiety and the relationships between changes in anxiety and changes in fluency in 11 subjects with a history of developmental stuttering. The randomized, double blind, placebo-controlled crossover study that was designed had to be terminated prior to completion due to severe side effects following withdrawal from paroxetine. Even with a reduced sample size (n=6), significant improvement in percent fluent speaking time (p=0.02) was found using a telephone task between baseline and pimozide (n=6), with average duration of dysfluencies significantly shorter (p=0.04) but no significant difference in the estimated number of dysfluencies per minute. This significant improvement was associated with non-significant increases in generalized anxiety, but non-significant decreases in speech-related anxiety. No significant differences were found in fluency between baseline and paroxetine (n=5). These preliminary results suggest that fluency improvement is more likely to be mediated by dopaminergic rather than serotonergic mechanisms. Due to its side effects, however, pimozide may be considered a risk for treatment of stuttering. EDUCATIONAL OBJECTIVES: As a result of reading this paper the reader will describe and explain: (1) how medications may affect fluency and the rationale for selecting medications for treatment trials; (2) the interrelationship between fluency and anxiety; and (3) factors important in developing clinical trials using medications. JF - Journal of fluency disorders AU - Stager, Sheila V AU - Calis, Karim AU - Grothe, Dale AU - Bloch, Meir AU - Berensen, Nannette M AU - Smith, Paul J AU - Braun, Allen AD - Voice and Speech Section, NIDCD, Bethesda, MD 20892-1416, USA. sstager@mfa.gwu.edu Y1 - 2005 PY - 2005 DA - 2005 SP - 319 EP - 335 VL - 30 IS - 4 SN - 0094-730X, 0094-730X KW - Index Medicus KW - National Library of Medicine KW - Adult KW - *Anxiety KW - Cross-Over Studies KW - Dopamine Antagonists: pharmacology KW - *Dopamine Antagonists: therapeutic use KW - Double-Blind Method KW - Female KW - Humans KW - Male KW - Middle Aged KW - Paroxetine: adverse effects KW - Paroxetine: pharmacology KW - *Paroxetine: therapeutic use KW - Pimozide: pharmacology KW - *Pimozide: therapeutic use KW - Serotonin Uptake Inhibitors: adverse effects KW - Serotonin Uptake Inhibitors: pharmacology KW - *Serotonin Uptake Inhibitors: therapeutic use KW - *Stuttering: drug therapy KW - Stuttering: physiopathology KW - Stuttering: psychology KW - Substance Withdrawal Syndrome KW - Treatment Outcome KW - *Verbal Behavior: drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85395052?accountid=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+fluency+disorders&rft.atitle=Treatment+with+medications+affecting+dopaminergic+and+serotonergic+mechanisms%3A+effects+on+fluency+and+anxiety+in+persons+who+stutter.&rft.au=Stager%2C+Sheila+V%3BCalis%2C+Karim%3BGrothe%2C+Dale%3BBloch%2C+Meir%3BBerensen%2C+Nannette+M%3BSmith%2C+Paul+J%3BBraun%2C+Allen&rft.aulast=Stager&rft.aufirst=Sheila&rft.date=2005-01-01&rft.volume=30&rft.issue=4&rft.spage=319&rft.isbn=&rft.btitle=&rft.title=Journal+of+fluency+disorders&rft.issn=0094730X&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Genetic testing in Parkinson's disease. AN - 85389015; pmid-15503301 AB - Parkinson's disease (PD) is a common neurodegenerative disorder of adulthood characterized clinically by rigidity, bradykinesia, resting tremor, and postural instability. The annual incidence of PD ranges between 16 and 19 individuals per 100,000 (Twelves et al., Mov Disord 2003;18:19-31). Historically, PD has been commonly viewed as an idiopathic or environmentally triggered condition. However, as is true with most common conditions, there have been several families reported with PD who demonstrate a classic Mendelian pattern of inheritance. To date, nine genetic loci have been reported and four pathogenic genes have been identified: alpha-synuclein, parkin, DJ1, and PINK1. Families with alterations in these genes or linked sites demonstrate either recessive or dominant inheritance patterns and may have typical and/or atypical symptoms, with an age of onset extending from the second to the sixth decade. Commercial tests for parkin and alpha-synuclein mutations are now available. We predict that physicians, particularly neurologists, increasingly will be approached for information and referrals regarding genetic testing. To assist patients and their families, physicians will not only need to know when such testing is likely to yield a meaningful result but also be aware of the possible social and emotional consequences of testing. The following is a review of what is currently known about the genetics of PD within this context. We discuss what is known about genetic testing for Huntington's disease, a well-described model for genetic testing in a neurodegenerative disorder. We explore the utility, appropriateness, and possible implications of genetic testing for diagnostic and presymptomatic purposes.Published 2004 John Wiley & Sons. JF - Movement disorders : official journal of the Movement Disorder Society AU - McInerney-Leo, Aideen AU - Hadley, Donald W AU - Gwinn-Hardy, Katrina AU - Hardy, John AD - Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20952, USA. amcinern@mail.nih.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 1 EP - 10 VL - 20 IS - 1 SN - 0885-3185, 0885-3185 KW - National Library of Medicine KW - Family Health KW - Humans KW - Huntington Disease: diagnosis KW - Huntington Disease: genetics KW - Intracellular Signaling Peptides and Proteins KW - *Molecular Diagnostic Techniques: methods KW - *Nerve Tissue Proteins: genetics KW - Oncogene Proteins: genetics KW - *Parkinson Disease: diagnosis KW - Parkinson Disease: etiology KW - *Parkinson Disease: genetics KW - Protein Kinases: genetics KW - Synucleins KW - Ubiquitin-Protein Ligases: genetics KW - alpha-Synuclein UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85389015?accountid=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=Genetic+testing+in+Parkinson%27s+disease.&rft.au=McInerney-Leo%2C+Aideen%3BHadley%2C+Donald+W%3BGwinn-Hardy%2C+Katrina%3BHardy%2C+John&rft.aulast=McInerney-Leo&rft.aufirst=Aideen&rft.date=2005-01-01&rft.volume=20&rft.issue=1&rft.spage=1&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 - 2012-06-22 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Nuclear factor-KappaB as a common target and activator of oncogenes in head and neck squamous cell carcinoma. AN - 85374354; pmid-15608421 AB - Head and neck squamous cell carcinomas exhibit alterations in cell proliferation, survival (apoptosis), migration, angiogenesis and inflammation. The transcription factor nuclear factor-KappaB integrates multiple signals and regulates expression of multiple genes involved in these phenotypic responses, suggesting the hypothesis that nuclear factor-KappaB is an important molecular switch for development of head and neck squamous cell carcinoma. Nuclear factor-KappaB has been found to be constitutively activated, and a common target and activator of oncogenes in cancer. Because of its important role, activation of nuclear factor-KappaB by the proteasome and other signal molecules may provide targets for molecular therapy of squamous cell carcinoma and other cancers. JF - Advances in oto-rhino-laryngology AU - Chang, Angela A AU - Van Waes, Carter AD - National Institutes of Health Clinical Research Training Program, National Institute on Deafness and Other Communication Disorders, Bethesda, MD 20892, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 92 EP - 102 VL - 62 SN - 0065-3071, 0065-3071 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Antineoplastic Combined Chemotherapy Protocols: therapeutic use KW - Carcinoma, Squamous Cell: drug therapy KW - *Carcinoma, Squamous Cell: genetics KW - Carcinoma, Squamous Cell: mortality KW - Clinical Trials as Topic KW - Disease Models, Animal KW - Disease Progression KW - Female KW - Gene Expression Regulation, Neoplastic KW - Head and Neck Neoplasms: drug therapy KW - *Head and Neck Neoplasms: genetics KW - Head and Neck Neoplasms: mortality KW - Humans KW - Male KW - Mice KW - NF-kappa B: genetics KW - *NF-kappa B: metabolism KW - Neoplasm Staging KW - Oncogenes: drug effects KW - Oncogenes: genetics KW - Prognosis KW - Risk Factors KW - Sensitivity and Specificity KW - Survival Analysis KW - *Tumor Markers, Biological: analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85374354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+oto-rhino-laryngology&rft.atitle=Nuclear+factor-KappaB+as+a+common+target+and+activator+of+oncogenes+in+head+and+neck+squamous+cell+carcinoma.&rft.au=Chang%2C+Angela+A%3BVan+Waes%2C+Carter&rft.aulast=Chang&rft.aufirst=Angela&rft.date=2005-01-01&rft.volume=62&rft.issue=&rft.spage=92&rft.isbn=&rft.btitle=&rft.title=Advances+in+oto-rhino-laryngology&rft.issn=00653071&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Language and Genetics: Needs and Opportunities AN - 85334363; llba-200504231 AB - This paper describes the next steps for establishing detailed, useful behavioral phenotypes & for moving forward in the study of the relationships among genes, the environment, & language disorders. Key issues are recognizing the continuum of language behaviors to accurately describe disorders & the spectrum of typical development. A coordinated plan with foundational studies that address definition, measurement, design, & analytical methods is needed. Researcher capacity must be increased, & a greater focus on communication across disciplines to successfully accomplish interdisciplinary research is required. Language is not static, even in disorders; thus, we must study change over time. It is necessary to think about behavioral phenotypes in terms of developmental trajectories. Finally, data sharing & ethical & legal issues must be addressed. 1 Reference. Adapted from the source document JF - Applied Psycholinguistics AU - McCardle, Peggy AU - Cooper, Judith AU - Freund, Lisa AD - National Instit Child Health & Human Development, National Instits Health, Bethesda, MD mcardlp@mail.nih.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 129 EP - 135 VL - 26 IS - 1 SN - 0142-7164, 0142-7164 KW - *Genetics (27600) KW - *Research Design (72950) KW - *Diagnosis (18540) KW - *Developmental Disabilities (18450) KW - *Learning Environment (45880) KW - *Language Pathology (43250) KW - article KW - 6410: language-pathological and normal; language-pathological and normal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85334363?accountid=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=Applied+Psycholinguistics&rft.atitle=Language+and+Genetics%3A+Needs+and+Opportunities&rft.au=McCardle%2C+Peggy%3BCooper%2C+Judith%3BFreund%2C+Lisa&rft.aulast=McCardle&rft.aufirst=Peggy&rft.date=2005-01-01&rft.volume=26&rft.issue=1&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Applied+Psycholinguistics&rft.issn=01427164&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2005-04-01 N1 - Last updated - 2014-06-17 N1 - CODEN - APPSDZ N1 - SubjectsTermNotLitGenreText - *Genetics (27600); *Learning Environment (45880); *Language Pathology (43250); *Diagnosis (18540); *Research Design (72950); *Developmental Disabilities (18450) ER - TY - JOUR T1 - Synaptic distribution of the endocytic accessory proteins AP180 and CALM. AN - 85306541; pmid-15558718 AB - Clathrin-coated vesicles mediate a variety of endocytosis pathways in cells, including endocytic events at synapses. AP180 and clathrin assembly lymphoid myeloid leukemia protein (CALM) are clathrin accessory proteins that promote the formation of clathrin-coated vesicles. Both proteins bind to membrane lipids through their epsin N-terminal homology domains and interact with clathrin and related protein components through their carboxyl-terminal peptide motifs. We examine their neuronal expression and synaptic distribution. We show that both proteins are detected in synapses but demonstrate different distribution patterns. AP180 is located predominantly in presynaptic profiles, whereas CALM is found nonselectively in pre- and postsynaptic profiles and also in perisynaptic processes. These observations reveal an unexpected relationship between AP180 and the presumed non-neuronal homologue CALM. We propose that both AP180 and CALM function as endocytic accessory proteins at synapses, but each may regulate distinct clathrin pathways. JF - The Journal of Comparative Neurology AU - Yao, Pamela J AU - Petralia, Ronald S AU - Bushlin Ittai AU - Wang, Yue AU - Furukawa Katsutoshi AD - Laboratory of Neurosciences, National Institute on Aging/National Institutes of Health, Baltimore, Maryland 21224. PY - 2005 SP - 58 EP - 69 VL - 481 IS - 1 SN - 0021-9967, 0021-9967 KW - Animals KW - Synapses KW - Hippocampus KW - Presynaptic Terminals KW - Tissue Distribution KW - Reverse Transcriptase Polymerase Chain Reaction KW - Clathrin-Coated Vesicles KW - Rats KW - Endocytosis KW - Comparative Study KW - Cells, Cultured KW - Neurons KW - Monomeric Clathrin Assembly Proteins KW - PC12 Cells UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85306541?accountid=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+Comparative+Neurology&rft.atitle=Synaptic+distribution+of+the+endocytic+accessory+proteins+AP180+and+CALM.&rft.au=Yao%2C+Pamela+J%3BPetralia%2C+Ronald+S%3BBushlin+Ittai%3BWang%2C+Yue%3BFurukawa+Katsutoshi&rft.aulast=Yao&rft.aufirst=Pamela&rft.date=2005-01-01&rft.volume=481&rft.issue=1&rft.spage=58&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Comparative+Neurology&rft.issn=00219967&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Pregnancy outcomes in smokers who develop pre-eclampsia AN - 745932735; 6618901 AB - Maternal smoking reduces the risk of pre-eclampsia, but has been reported to increase the risk of adverse outcomes related to the disease. We used data from the trial of Calcium for Pre-eclampsia Prevention (CPEP) to explore whether clinical manifestations of pre-eclampsia were altered by maternal smoking. CPEP was a randomised study of 4589 nulliparous women conducted in five US medical centres. Smoking history was obtained at study enrolment and women were monitored for the development of hypertension, proteinuria, and other medical complications. Among pre-eclamptic women (n = 274), the risk of severe disease was not elevated in smokers (adjusted odds ratio 0.87 [95% confidence interval (CI) 0.30, 2.51]). Compared with non-smokers, gestational age (days, cSE) at onset of pre-eclampsia was not reduced in smokers (264.8 c 1.5, and 268.2 c 5.5, respectively, P = 0.48). The smoking-attributable deficit in birthweight was not increased in pre-eclamptic women compared with normotensive women (97 g [95% CI -49, 244] and 185 g [95% CI 141, 229] respectively). In conclusion, among women who developed pre-eclampsia, smoking during pregnancy was not associated with disease severity. We found no evidence that pre-eclampsia and smoking act synergistically to restrict fetal growth. JF - Paediatric and Perinatal Epidemiology AU - Beste, Lauren A AU - England, Lucinda J AU - Schisterman, Enrique F AU - Qian, Cong AU - Yu, Kai F AU - Levine, Richard J AD - Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, lengland@cdc.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 12 EP - 18 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 19 IS - 1 SN - 0269-5022, 0269-5022 KW - Risk Abstracts KW - Smoking KW - risk reduction KW - Historical account KW - Age KW - complications KW - Calcium KW - hypertension KW - prevention KW - Pregnancy KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/745932735?accountid=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=Paediatric+and+Perinatal+Epidemiology&rft.atitle=Pregnancy+outcomes+in+smokers+who+develop+pre-eclampsia&rft.au=Beste%2C+Lauren+A%3BEngland%2C+Lucinda+J%3BSchisterman%2C+Enrique+F%3BQian%2C+Cong%3BYu%2C+Kai+F%3BLevine%2C+Richard+J&rft.aulast=Beste&rft.aufirst=Lauren&rft.date=2005-01-01&rft.volume=19&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Paediatric+and+Perinatal+Epidemiology&rft.issn=02695022&rft_id=info:doi/10.1111%2Fj.1365-3016.2004.00617.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-07-01 N1 - SuppNotes - Tables, 4; references, 19. N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Historical account; risk reduction; Smoking; Age; Calcium; complications; hypertension; prevention; Pregnancy DO - http://dx.doi.org/10.1111/j.1365-3016.2004.00617.x ER - TY - JOUR T1 - Compliance and toxicity of adjuvant CMF in elderly breast cancer patients: a single-center experience AN - 744693610; 6214863 AB - Background: Few data are available on compliance and safety of adjuvant chemotherapy when indicated in elderly breast cancer patients; CMF (cyclophosphamide, methotrexate, fluorouracil) can be reasonably considered the most widely accepted standard of treatment. Methods: We retrospectively reviewed compliance and safety of adjuvant CMF in patients older than 60. The treatment was indicated if patients had no severe comorbidity, a high-risk of recurrence, and were younger than 75. Toxicity was coded by NCI-CTC. Toxicity and compliance were compared between two age subgroups (= 65) by Fisher exact test and exact Wilcoxon rank-sum test. Results: From March 1991 to March 2002, 180 patients were identified, 100 older than 60 and younger than 65, and 80 aged 65 or older. Febrile neutropenia was more frequent among older patients (p = 0.05). Leukopenia, neutropenia, nausea, cardiac toxicity and thrombophlebitis tended to be more frequent or severe among elderlies, while mucositis tended to be more evident among younger patients, all not significantly. Almost one half (47%) of the older patients receiving concomitant radiotherapy experienced grade 3-4 haematological toxicity. Compliance was similar in the two groups, with 6 cycles administered in 86% and 79%, day-8 chemotherapy omitted at least once in 36% and 39%, dose reduction in 27% and 38%, prolonged treatment duration (>= 29 weeks) in 10% and 11% and need of G-CSF in 9% and 18%, among younger and older patients, respectively. Conclusions: Our data show that, in a highly selected population of patients 65 or more years old, CMF is as feasible as in patients older than 60 and younger than 65, but with a relevant burden of toxicity. We suggest that prospective trials in elderly patients testing less toxic treatment schemes are mandatory before indicating adjuvant chemotherapy to all elderly patients with significant risk of breast cancer recurrence. JF - BMC Cancer AU - De Maio, Ermelinda AU - Gravina, Adriano AU - Pacilio, Carmen AU - Amabile, Gerardo AU - Labonia, Vincenzo AU - Landi, Gabriella AU - Nuzzo, Francesco AU - Rossi, Emanuela AU - D'Aiuto, Giuseppe AU - Capasso, Immacolata AU - Rinaldo, Massimo AU - Morrica, Brunello AU - Elmo, Massimo AU - Di Maio, Massimo AU - Perrone, Francesco AU - De Matteis, Andrea AD - Clinical Trials Unit, National Cancer Institute, Naples, Italy, e.demaio@unina.it Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 5 KW - Toxicology Abstracts KW - Heart KW - Age KW - Data processing KW - Mucositis KW - Chemotherapy KW - Radiotherapy KW - Granulocyte colony-stimulating factor KW - Adjuvants KW - Toxicity KW - Cyclophosphamide KW - Clinical trials KW - Neutropenia KW - Risk factors KW - Geriatrics KW - Breast cancer KW - Methotrexate KW - Risk groups KW - Nausea KW - Leukopenia KW - Thrombophlebitis KW - X 24310:Pharmaceuticals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/744693610?accountid=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=BMC+Cancer&rft.atitle=Compliance+and+toxicity+of+adjuvant+CMF+in+elderly+breast+cancer+patients%3A+a+single-center+experience&rft.au=De+Maio%2C+Ermelinda%3BGravina%2C+Adriano%3BPacilio%2C+Carmen%3BAmabile%2C+Gerardo%3BLabonia%2C+Vincenzo%3BLandi%2C+Gabriella%3BNuzzo%2C+Francesco%3BRossi%2C+Emanuela%3BD%27Aiuto%2C+Giuseppe%3BCapasso%2C+Immacolata%3BRinaldo%2C+Massimo%3BMorrica%2C+Brunello%3BElmo%2C+Massimo%3BDi+Maio%2C+Massimo%3BPerrone%2C+Francesco%3BDe+Matteis%2C+Andrea&rft.aulast=De+Maio&rft.aufirst=Ermelinda&rft.date=2005-01-01&rft.volume=5&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Cancer&rft.issn=1471-2407&rft_id=info:doi/10.1186%2F1471-2407-5-30 L2 - http://www.biomedcentral.com/14712407/5/30 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-07-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Heart; Age; Data processing; Mucositis; Chemotherapy; Radiotherapy; Cyclophosphamide; Toxicity; Adjuvants; Granulocyte colony-stimulating factor; Clinical trials; Neutropenia; Risk factors; Geriatrics; Risk groups; Methotrexate; Breast cancer; Nausea; Leukopenia; Thrombophlebitis DO - http://dx.doi.org/10.1186/1471-2407-5-30 ER - TY - JOUR T1 - Review article toxic oil syndrome: review of immune aspects of the disease. AN - 733749036; 18958659 AB - In 1981-1982, individuals in fourteen central and northwest provinces in Spain were affected by an illness that was eventually labeled toxic oil syndrome (TOS) by the World Health Organization. Thousands of individuals were diagnosed with, and 356 people eventually died from, the disease. The disease shares striking similarities with several autoimmune diseases, particularly eosinophilia-myalgia syndrome (EMS) and diffuse fasciitis with eosinophilia (DFE). As with many other autoimmune diseases, women were more severely affected than men and made up a significant portion of TOS-related deaths. While a number of etiologic agents were investigated, disease occurrence was found to be significantly associated with consumption of contaminated rapeseed oil produced by a particular refinery. Two compounds, 1,2-di-oleyl ester (DEPAP) and oleic anilide are considered to be biologically relevant contaminants that may contribute to disease development. Toxic oil syndrome was a three-phase disease with an initial non-necrotizing vasculitis in multiple organs. Suspected immune mechanisms in TOS include activation of T-cells, altered cytokine production, and several studies have associated disease severity with HLA-DR2 and polymorphisms in metabolism and immune response genes. While a number of animal models have been used to investigate the underlying immune mechanisms in TOS, only a few studies in rodents have demonstrated the classical symptoms of TOS. Biotransformation and oxidation of the parent compound(s) to reactive intermediates prior to induction of autoreactive pathways appears to be an important component of the disease process. These reactive intermediates could haptenate self-proteins and activate autoreactive T-cells, disrupt signal transduction, or induce apoptosis and necrosis to release abnormal forms of self-antigens. Although the TOS epidemic was limited to a discrete period of time, the origin of the contamination determined, and the spread of the disease halted by government intervention, the underlying immune mechanisms have yet to be elucidated. JF - Journal of immunotoxicology AU - Patterson, Rachel AU - Germolec, Dori AD - Laboratory of Molecular Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, North Carolina. Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - 51 EP - 58 VL - 2 IS - 1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/733749036?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotoxicology&rft.atitle=Review+article+toxic+oil+syndrome%3A+review+of+immune+aspects+of+the+disease.&rft.au=Patterson%2C+Rachel%3BGermolec%2C+Dori&rft.aulast=Patterson&rft.aufirst=Rachel&rft.date=2005-01-01&rft.volume=2&rft.issue=1&rft.spage=51&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotoxicology&rft.issn=1547-6901&rft_id=info:doi/10.1080%2F15476910590960143 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2012-10-02 N1 - Date created - 2008-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 DO - http://dx.doi.org/10.1080/15476910590960143 ER - TY - JOUR T1 - Stem cells and mammary cancer in mice. AN - 70183371; 17142858 AB - I have used the paradigm of mammary cancer induction by the mouse mammary tumor virus (MMTV) to illustrate the body of evidence that supports the hypothesis that mammary epithelial stem/progenitor cells represent targets for oncogenic transformation. Further, it is argued that this is not a special case applicable only to MMTV-induced mammary cancer, because MMTV acts as an environmental mutagen producing random interruptions in the somatic DNA of infected cells by insertion of proviral DNA copies. In addition to disrupting the host genome, the proviral DNA also influences gene expression through its associated enhancer sequences over significant inter-genome distances. Genes commonly affected by MMTV insertion in multiple individual tumors include the Wnt genes, the fibroblast growth factor (FGF) gene family, and the Notch gene family. All of these gene families are known to play essential roles in stem cell maintenance and behavior in a variety of organs. The MMTV-induced mutations accumulate in cells that are long-lived and possess the properties of stem cells, namely, self-renewal and the capacity to produce divergent epithelial progeny through asymmetric division. The evidence shows that epithelial cells with these properties are present in normal mammary glands, may be infected with MMTV, and become transformed to produce epithelial hyperplasia through MMTV-induced mutagenesis and progress to frank mammary malignancy. Retroviral marking via MMTV proviral insertion demonstrates that this process progresses from a single mammary epithelial cell that possesses all the features ascribed to tissue-specific stem cells. JF - Stem cell reviews AU - Smith, Gibert H AD - Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, MD 10892, USA. gs4d@nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 215 EP - 223 VL - 1 IS - 3 SN - 1550-8943, 1550-8943 KW - Neoplasm Proteins KW - 0 KW - Index Medicus KW - Mammary Neoplasms, Experimental -- ultrastructure KW - Epithelial Cells -- virology KW - Epithelial Cells -- ultrastructure KW - Epithelial Cells -- metabolism KW - Neoplasm Proteins -- biosynthesis KW - Animals KW - Neoplasm Proteins -- genetics KW - Mammary Neoplasms, Experimental -- genetics KW - Mice KW - Mammary Neoplasms, Experimental -- virology KW - Mammary Neoplasms, Experimental -- metabolism KW - Female KW - Gene Expression Regulation, Neoplastic -- genetics KW - Mammary Tumor Virus, Mouse -- metabolism KW - Mammary Neoplasms, Animal -- genetics KW - Cell Transformation, Viral -- genetics KW - Mammary Neoplasms, Animal -- metabolism KW - Neoplastic Stem Cells -- virology KW - Mammary Neoplasms, Animal -- ultrastructure KW - Virus Integration -- genetics KW - Mammary Neoplasms, Animal -- virology KW - Mutagenesis, Insertional KW - Neoplastic Stem Cells -- metabolism KW - Mammary Tumor Virus, Mouse -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70183371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cell+reviews&rft.atitle=Stem+cells+and+mammary+cancer+in+mice.&rft.au=Smith%2C+Gibert+H&rft.aulast=Smith&rft.aufirst=Gibert&rft.date=2005-01-01&rft.volume=1&rft.issue=3&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Stem+cell+reviews&rft.issn=15508943&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2007-01-23 N1 - Date created - 2006-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The contribution of epidermal stem cells to skin cancer. AN - 70182967; 17142859 AB - Tumors arising from the skin are of multiple phenotypes, with differing degrees of malignant potential. In mouse models of skin carcinogenesis, tumors of squamous phenotype are the most common; however, human disease indicates that multiple phenotypes may arise from a common pool of stem cells that are then influenced by epigenetic factors. The use of transgenic and knockout gene technologies with mice is unraveling some of the specific genes regulating fate determination in stem cells other than squamous lineage, including basal cell carcinoma and sebaceous adenomas. The following review examines the evidence for the stem cell origin of epidermal tumors and the contribution of some specific gene families toward stem cell fate decisions during epidermal tumor progression. JF - Stem cell reviews AU - Gerdes, Michael J AU - Yuspa, Stuart H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute Bethesda, MD 20892, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 225 EP - 231 VL - 1 IS - 3 SN - 1550-8943, 1550-8943 KW - Index Medicus KW - Animals KW - Humans KW - Disease Models, Animal KW - Mice KW - Mice, Knockout KW - Gene Expression Regulation, Neoplastic -- genetics KW - Skin Neoplasms -- genetics KW - Carcinoma, Basal Cell -- genetics KW - Neoplastic Stem Cells -- pathology KW - Adenocarcinoma, Sebaceous -- pathology KW - Skin Neoplasms -- pathology KW - Epidermis -- pathology KW - Epigenesis, Genetic KW - Carcinoma, Basal Cell -- pathology KW - Adenocarcinoma, Sebaceous -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70182967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+cell+reviews&rft.atitle=The+contribution+of+epidermal+stem+cells+to+skin+cancer.&rft.au=Gerdes%2C+Michael+J%3BYuspa%2C+Stuart+H&rft.aulast=Gerdes&rft.aufirst=Michael&rft.date=2005-01-01&rft.volume=1&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Stem+cell+reviews&rft.issn=15508943&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2007-01-23 N1 - Date created - 2006-12-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lead exposure as a risk factor for amyotrophic lateral sclerosis. AN - 70173119; 16909025 AB - The etiology of amyotrophic lateral sclerosis (ALS) likely involves an environmental component. We qualitatively assessed literature on ALS and lead exposure. Problems of study design make case reports and studies of lead in blood or tissues difficult to interpret. Most previous case-control studies found an association of ALS with self-reported occupational exposure to lead, with increased risks of 2- to >4-fold. However, these results may have been affected by recall bias. To address inconsistencies among published reports, we used both lead biomarkers and interview data to assess lead exposure, and we evaluated the role of genetic susceptibility to lead. We conducted a case-control study in New England in 1993-1996 with 109 ALS cases and 256 population-based controls. We measured blood and bone lead levels, the latter using X-ray fluorescence, and interviewed participants regarding sources of lead exposure. In our study, ALS was associated with self-reported occupational lead exposure, with a dose response for cumulative days of exposure. ALS was also associated with blood and bone lead levels, with a 1.9-fold increase in risk for each mug/dl increment in blood lead and a 2.3- to 3.6-fold increase for each doubling of bone lead. A polymorphism in the delta-aminolevulinic acid dehydratase gene was associated with a 1.9-fold increase in ALS risk. These results, together with previous studies, suggest that lead exposure plays a role in the etiology of ALS. An increase in mobilization of lead from bone into blood may play a role in the acute onset of disease. JF - Neuro-degenerative diseases AU - Kamel, F AU - Umbach, D M AU - Hu, H AU - Munsat, T L AU - Shefner, J M AU - Taylor, J A AU - Sandler, D P AD - National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA. kamel@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 195 EP - 201 VL - 2 IS - 3-4 SN - 1660-2854, 1660-2854 KW - Lead KW - 2P299V784P KW - Porphobilinogen Synthase KW - EC 4.2.1.24 KW - Index Medicus KW - Polymorphism, Genetic KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Case-Control Studies KW - Middle Aged KW - Genetic Predisposition to Disease KW - Porphobilinogen Synthase -- genetics KW - Mutation KW - Male KW - Female KW - Lead -- adverse effects KW - Occupational Exposure -- adverse effects KW - Lead -- analysis KW - Amyotrophic Lateral Sclerosis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70173119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuro-degenerative+diseases&rft.atitle=Lead+exposure+as+a+risk+factor+for+amyotrophic+lateral+sclerosis.&rft.au=Kamel%2C+F%3BUmbach%2C+D+M%3BHu%2C+H%3BMunsat%2C+T+L%3BShefner%2C+J+M%3BTaylor%2C+J+A%3BSandler%2C+D+P&rft.aulast=Kamel&rft.aufirst=F&rft.date=2005-01-01&rft.volume=2&rft.issue=3-4&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Neuro-degenerative+diseases&rft.issn=16602854&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-09-26 N1 - Date created - 2006-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Measuring the health consequences of alcohol consumption: current needs and methodological challenges. AN - 70150784; 16508279 AB - Extensive research has shown that alcohol consumption leads to poor health and premature death through its causal or contributing roles in numerous chronic health conditions and acute health outcomes, including various cancers, liver disease, and injuries. Paradoxically, advances in understanding of the causal associations between alcohol consumption and various conditions have complicated our ability to discern trends in the health consequences of alcohol consumption over time. Four distinct needs for information on alcohol's role in causing adverse health outcomes are identified. Estimates of alcohol-attributable mortality from two US studies are compared and differences identified. Differences in the conditions included and alcohol-attributable fractions employed accounted for large differences in the estimated alcohol-attributable mortality for several health outcomes. Despite the broad consensus on many health consequences of alcohol consumption, further research is needed to clarify the conditions that are caused by alcohol consumption, magnitudes of causal relationships, and effects of different patterns of consumption and individual characteristics. Comparisons over time are needed to identify areas where improvements in public health may be occurring or are most needed, to support evaluation of specific interventions, and to encourage the public awareness of alcohol problems that is necessary to change attitudes and behaviors involving alcohol consumption. Copyright 2005 S. Karger AG, Basel. JF - Digestive diseases (Basel, Switzerland) AU - Bloss, Gregory AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD 20892-9304, USA. gbloss@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 162 EP - 169 VL - 23 IS - 3-4 SN - 0257-2753, 0257-2753 KW - Index Medicus KW - Severity of Illness Index KW - Humans KW - Health Status KW - Aged KW - Needs Assessment KW - Age Distribution KW - Risk Factors KW - Adult KW - Middle Aged KW - United States -- epidemiology KW - Sex Distribution KW - Female KW - Male KW - Survival Analysis KW - Alcohol-Related Disorders -- diagnosis KW - Alcohol Drinking -- adverse effects KW - Alcohol-Related Disorders -- prevention & control KW - Health Education -- organization & administration KW - Cause of Death KW - Alcohol-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70150784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Digestive+diseases+%28Basel%2C+Switzerland%29&rft.atitle=Measuring+the+health+consequences+of+alcohol+consumption%3A+current+needs+and+methodological+challenges.&rft.au=Bloss%2C+Gregory&rft.aulast=Bloss&rft.aufirst=Gregory&rft.date=2005-01-01&rft.volume=23&rft.issue=3-4&rft.spage=162&rft.isbn=&rft.btitle=&rft.title=Digestive+diseases+%28Basel%2C+Switzerland%29&rft.issn=02572753&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-07-07 N1 - Date created - 2006-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. AN - 70138101; 16596792 AB - Increasing interest in the biology, chemistry, pharmacology, and toxicology of cannabinoids and in the development of cannabinoid medications necessitates an understanding of cannabinoid pharmacokinetics and disposition into biological fluids and tissues. A drug's pharmacokinetics determines the onset, magnitude, and duration of its pharmacodynamic effects. This review of cannabinoid pharmacokinetics encompasses absorption following diverse routes of administration and from different drug formulations, distribution of analytes throughout the body, metabolism by different tissues and organs, elimination from the body in the feces, urine, sweat, oral fluid, and hair, and how these processes change over time. Cannabinoid pharmacokinetic research has been especially challenging due to low analyte concentrations, rapid and extensive metabolism, and physicochemical characteristics that hinder the separation of drugs of interest from biological matrices--and from each other--and lower drug recovery due to adsorption of compounds of interest to multiple surfaces. delta9-Tetrahydrocannabinol, the primary psychoactive component of Cannabis sativa, and its metabolites 11-hydroxy-delta9-tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol are the focus of this chapter, although cannabidiol and cannabinol, two other cannabinoids with an interesting array of activities, will also be reviewed. Additional material will be presented on the interpretation of cannabinoid concentrations in human biological tissues and fluids following controlled drug administration. JF - Handbook of experimental pharmacology AU - Huestis, M A AD - Chemistry and Drug Metabolism, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. mhuestis@intra.nida.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 657 EP - 690 IS - 168 SN - 0171-2004, 0171-2004 KW - Cannabidiol KW - 19GBJ60SN5 KW - Dronabinol KW - 7J8897W37S KW - Cannabinol KW - 7UYP6MC9GH KW - Index Medicus KW - Animals KW - Sweat -- metabolism KW - Half-Life KW - Humans KW - Hair -- metabolism KW - Absorption KW - Liver -- metabolism KW - Tissue Distribution KW - Marijuana Smoking KW - Cannabinol -- pharmacokinetics KW - Dronabinol -- pharmacokinetics KW - Cannabinol -- administration & dosage KW - Dronabinol -- administration & dosage KW - Cannabidiol -- administration & dosage KW - Cannabidiol -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70138101?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Handbook+of+experimental+pharmacology&rft.atitle=Pharmacokinetics+and+metabolism+of+the+plant+cannabinoids%2C+delta9-tetrahydrocannabinol%2C+cannabidiol+and+cannabinol.&rft.au=Huestis%2C+M+A&rft.aulast=Huestis&rft.aufirst=M&rft.date=2005-01-01&rft.volume=&rft.issue=168&rft.spage=657&rft.isbn=&rft.btitle=&rft.title=Handbook+of+experimental+pharmacology&rft.issn=01712004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-04-19 N1 - Date created - 2006-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The liver in HIV in Africa. AN - 69088605; 16430201 AB - As access to antiretroviral therapy improves across the African continent, liver disease is emerging as an important cause of morbidity and mortality among HIV-infected individuals. Although coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV), along with highly active antiretroviral therapy (HAART)-induced hepatotoxicity appear to be the major causes of liver disease in this population, other diseases endemic to Africa with hepatic manifestations are influenced by HIV infection as well. In this review we present the available data on liver disease in HIV-infected populations in Africa and discuss relevant data from the rest of the world. In addition, we highlight important areas for further study. JF - Antiviral therapy AU - Feld, Jordan J AU - Ocama, Ponsiano AU - Ronald, Allan AD - Infectious Disease Clinic, Department of Medicine, Mulago Hospital, Kampala, Uganda. feldj@niddk.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 953 EP - 965 VL - 10 IS - 8 SN - 1359-6535, 1359-6535 KW - Anti-HIV Agents KW - 0 KW - Index Medicus KW - Anti-HIV Agents -- therapeutic use KW - Africa -- epidemiology KW - Humans KW - Drug-Induced Liver Injury, Chronic KW - Anti-HIV Agents -- adverse effects KW - Hepatitis C -- epidemiology KW - Comorbidity KW - Hepatitis, Viral, Human -- epidemiology KW - Hepatitis B -- epidemiology KW - Liver Diseases -- epidemiology KW - HIV Infections -- drug therapy KW - Liver Diseases -- etiology KW - HIV Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69088605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+liver+in+HIV+in+Africa.&rft.au=Feld%2C+Jordan+J%3BOcama%2C+Ponsiano%3BRonald%2C+Allan&rft.aulast=Feld&rft.aufirst=Jordan&rft.date=2005-01-01&rft.volume=10&rft.issue=8&rft.spage=953&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 - 2006-02-23 N1 - Date created - 2006-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nucleoside modification and concerted mutagenesis of the human A3 adenosine receptor to probe interactions between the 2-position of adenosine analogs and Gln167 in the second extracellular loop. AN - 69087313; 16438031 AB - Residues of the second extracellular loop are believed to be important for ligand recognition in adenosine receptors. Molecular modeling studies have suggested that one such residue, Gln167 of the human A3 receptor, is in proximity to the C2 moiety of some adenosine analogs when bound. Here this putative interaction was systematically explored using a neoceptor strategy, i.e., by site-directed mutagenesis and examination of the affinities of nucleosides modified to have complementary functionality. Gln167 was mutated to Ala, Glu, and Arg, while the 2-position of several adenosine analogs was substituted with amine or carboxylic acid groups. All compounds tested lost affinity to the mutant receptors in comparison to the wild type. However, comparing affinities among the mutant receptors, several compounds bearing charge at the 2-position demonstrated preferential affinity for the mutant receptor bearing a residue of complementary charge. 13, with a positively-charged C2 moiety, displayed an 8.5-fold increase in affinity at the Q167E mutant receptor versus the Q167R mutant receptor Preferential affinity for specific mutant receptors was also observed for 8 and 12. The data suggests that a direct contact is made between the C2 substituent of some charged ligands and the mutant receptor bearing the opposite charge at position 167. JF - Nucleosides, nucleotides & nucleic acids AU - Duong, Heng T AU - Gao, Zhan-Guo 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, MD 20892-0810, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 1507 EP - 1517 VL - 24 IS - 10-12 SN - 1525-7770, 1525-7770 KW - Receptors, Purinergic P1 KW - 0 KW - Glutamine KW - 0RH81L854J KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Humans KW - Glutamine -- genetics KW - Protein Binding -- genetics KW - Cell Line KW - Receptors, Purinergic P1 -- genetics KW - Adenosine -- pharmacology KW - Mutagenesis, Site-Directed -- methods KW - Adenosine -- analogs & derivatives KW - Point Mutation KW - Receptors, Purinergic P1 -- metabolism KW - Amino Acid Substitution KW - Adenosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69087313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nucleoside+modification+and+concerted+mutagenesis+of+the+human+A3+adenosine+receptor+to+probe+interactions+between+the+2-position+of+adenosine+analogs+and+Gln167+in+the+second+extracellular+loop.&rft.au=Duong%2C+Heng+T%3BGao%2C+Zhan-Guo%3BJacobson%2C+Kenneth+A&rft.aulast=Duong&rft.aufirst=Heng&rft.date=2005-01-01&rft.volume=24&rft.issue=10-12&rft.spage=1507&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 - 2006-03-24 N1 - Date created - 2006-01-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antitumor activity of Nitronaphthal-NU, a novel mixed-function agent. AN - 69076529; 16416597 AB - Nitronaphthal-NU (Compound 1) was synthesized as a mixed-function antitumor agent based on the structures of the clinical drug CCNU and experimental compound Mitonafide. In vitro screening in four human tumor cell lines namely SNB-78 CNS, HOP-62 Lung, T47D Breast and SiHa - cervix revealed significant cytotoxicity in the former two cell lines much greater than CCNU and comparable to Mitonafide used as standards. In vivo antitumoral potency assessed in the murine ascites tumors Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times of drug treated (T) over untreated control (C) mice, revealed highly significant (p<0.001) tumor regression effects greater than standards. Life span of mice bearing advanced tumor for 10 days before the drug challenge was also considerably increased. Its toxicity was assessed in vivo in normal and S-180 bearing mice by measuring drug-induced changes in haematological parameters, femoral bone marrow and splenic cellularities as well as hepatotoxicity and nephrotoxicity sequentially on days 9, 15 and 21 following drug treatment at the optimum dose of 50 mg/kg from day 1 to 7. Results indicate that it did not adversely affect haematopoiesis. The other parameters were within normal limit. The compound comparable to standards inhibited the synthesis of DNA and RNA in S-1 80 tumor cells. JF - Journal of experimental therapeutics & oncology AU - Samanta, Suva AU - Pain, Anindita AU - Dutta, Sushanta AU - Saxena, Ajit Kumar AU - Shanmugavel, Mutiah AU - Pandita, Renu Moti AU - Qazi, Gulam Nabi AU - Sanyal, Utpal AD - Department of Anticancer Drug Development, Chittaranjan National Cancer Institute, Calcutta-700026, India. Y1 - 2005 PY - 2005 DA - 2005 SP - 15 EP - 22 VL - 5 IS - 1 SN - 1359-4117, 1359-4117 KW - Antineoplastic Agents KW - 0 KW - DNA, Neoplasm KW - Imides KW - Isoquinolines KW - Naphthalenes KW - Naphthalimides KW - RNA, Neoplasm KW - nitronaphthal-NU KW - mitonafide KW - 06Q0V17SI9 KW - Lomustine KW - 7BRF0Z81KG KW - DNA KW - 9007-49-2 KW - Thymidine KW - VC2W18DGKR KW - Uridine KW - WHI7HQ7H85 KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Animals KW - Drug Screening Assays, Antitumor KW - DNA -- metabolism KW - Humans KW - Lomustine -- therapeutic use KW - Mice KW - Cell Line, Tumor KW - Alkylation KW - DNA -- drug effects KW - Thymidine -- metabolism KW - Neoplasm Transplantation KW - Isoquinolines -- therapeutic use KW - Sarcoma 180 -- metabolism KW - Uridine -- metabolism KW - Drug Synergism KW - DNA, Neoplasm -- biosynthesis KW - Imides -- therapeutic use KW - Naphthalenes -- pharmacology KW - Antineoplastic Agents -- chemical synthesis KW - Naphthalenes -- chemical synthesis KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69076529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+therapeutics+%26+oncology&rft.atitle=Antitumor+activity+of+Nitronaphthal-NU%2C+a+novel+mixed-function+agent.&rft.au=Samanta%2C+Suva%3BPain%2C+Anindita%3BDutta%2C+Sushanta%3BSaxena%2C+Ajit+Kumar%3BShanmugavel%2C+Mutiah%3BPandita%2C+Renu+Moti%3BQazi%2C+Gulam+Nabi%3BSanyal%2C+Utpal&rft.aulast=Samanta&rft.aufirst=Suva&rft.date=2005-01-01&rft.volume=5&rft.issue=1&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+therapeutics+%26+oncology&rft.issn=13594117&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-03-10 N1 - Date created - 2006-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ADP-ribosylation factor domain protein 1 (ARD1), a multifunctional protein with ubiquitin E3 ligase, GAP, and ARF domains. AN - 69068867; 16413270 AB - ADP-ribosylation factor domain protein 1 (ARD1) is a multifunctional protein that belongs to the family of 20-kDa ARF proteins. The ARD1 gene encodes a 64-kDa protein with a structure comprising an 18-kDa ADP-ribosylation factor (ARF) domain at the C-terminus (amino acids 403-574), and a 46-kDa N-terminal domain (amino acids 1-402) that contains, from the translation start site, a RING finger domain, two predicted B-Boxes, and a coiled-coil protein interaction motif, which places it among the TRIM (tripartite motif) or RBCC (RING, B-Box, coiled-coil) protein families. Recombinant ARD1 (amino acids 1-574) or its RING finger domain (amino acids 1-110) produced polyubiquitylated proteins when incubated in vitro with a mammalian E1, an E2 enzyme (UbcH6 or UbcH5a, -5b, or -5c), ATP, and ubiquitin. Via its C-terminal ARF domain, recombinant ARD1 binds guanine nucleotides, through which it can enhance, in a GTP-dependent manner, cholera toxin ADP-ribosyltransferase activity. Unlike ARFs, ARD1, but not its ARF domain, exhibits significant GTPase activity. Hydrolysis of GTP bound to the C-terminal ARF domain was stimulated by addition of the 46-kDa N-terminal domain (amino acids 1-402) via its GTPase activating protein (GAP) activity. The rate of GDP dissociation from the C-terminal ARF domain in ARD1, is slowed by the adjacent 15 amino acids, which act as a GDP-dissociation inhibitor (GDI) domain. Cytohesin-1, known already as a guanine nucleotide-exchange factor (GEF) ARF activator, also specifically activated recombinant human ARD1, via activation of the ARF domain. Overexpressed ARD1 fusion proteins were associated with structures resembling lysosomes and Golgi membranes, as well as the nucleus, in different types of cells, and sequences potentially responsible for the intracellular localizations were identified. JF - Methods in enzymology AU - Vichi, Alessandro AU - Moss, Joel AU - Vaughan, Martha AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 195 EP - 206 VL - 404 SN - 0076-6879, 0076-6879 KW - DNA-Binding Proteins KW - 0 KW - GTPase-Activating Proteins KW - Recombinant Proteins KW - TRIM23 protein, human KW - Agmatine KW - 70J407ZL5Q KW - Guanosine Triphosphate KW - 86-01-1 KW - Cholera Toxin KW - 9012-63-9 KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Rats KW - Recombinant Proteins -- isolation & purification KW - Animals KW - GTPase-Activating Proteins -- metabolism KW - Recombinant Proteins -- biosynthesis KW - DNA-Binding Proteins -- chemistry KW - Agmatine -- metabolism KW - Humans KW - Ubiquitin-Protein Ligases -- metabolism KW - Protein Structure, Tertiary KW - Guanosine Triphosphate -- metabolism KW - Cholera Toxin -- metabolism KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69068867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=ADP-ribosylation+factor+domain+protein+1+%28ARD1%29%2C+a+multifunctional+protein+with+ubiquitin+E3+ligase%2C+GAP%2C+and+ARF+domains.&rft.au=Vichi%2C+Alessandro%3BMoss%2C+Joel%3BVaughan%2C+Martha&rft.aulast=Vichi&rft.aufirst=Alessandro&rft.date=2005-01-01&rft.volume=404&rft.issue=&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-03-14 N1 - Date created - 2006-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The genetics of ATP-binding cassette transporters. AN - 69061605; 16399363 AB - The ATP-binding cassette (ABC) superfamily consists of membrane proteins that transport a wide variety of substrates across membranes. Mutations in ABC transporters cause or contribute to a number of different Mendelian disorders, including adrenoleukodystrophy, cystic fibrosis, retinal degeneration, cholesterol, and bile transport defects. In addition, the genes are involved in an increasing number of complex disorders. The proteins play essential roles in the protection of organisms from toxic metabolites and compounds in the diet and are involved in the transport of compounds across the intestine, blood-brain barrier, and the placenta. There are 48 ABC genes in the human genome divided into seven subfamilies based in gene structure, amino acid alignment, and phylogenetic analysis. These seven subfamilies are found in all other sequenced eukaryotic genomes and are of ancient origin. Further characterization of all ABC genes from humans and model organisms will lead to additional insights into normal physiology and human disease. JF - Methods in enzymology AU - Dean, Michael AD - Human Genetics Section, Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 409 EP - 429 VL - 400 SN - 0076-6879, 0076-6879 KW - Cholesterol KW - 97C5T2UQ7J KW - Index Medicus KW - Cholesterol -- metabolism KW - Humans KW - Mutation KW - Genetic Diseases, Inborn -- metabolism KW - ATP-Binding Cassette Transporters -- classification KW - ATP-Binding Cassette Transporters -- metabolism KW - Immune System Diseases -- genetics KW - Genetic Diseases, Inborn -- genetics KW - ATP-Binding Cassette Transporters -- genetics KW - Immune System Diseases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69061605?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=The+genetics+of+ATP-binding+cassette+transporters.&rft.au=Dean%2C+Michael&rft.aulast=Dean&rft.aufirst=Michael&rft.date=2005-01-01&rft.volume=400&rft.issue=&rft.spage=409&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-02-01 N1 - Date created - 2006-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - UDP-glucuronosyltransferases: gene structures of UGT1 and UGT2 families. AN - 69059770; 16399340 AB - In human, rat, and mice, a UGT1 complex locus provides for developmental-, inducer-, and cell-specific synthesis of a family of chemical-detoxifying isozymes, UDP-glucuronosyltransferases, which prevent toxicities, mutagenesis, and/or carcinogenesis. Between 10 and 14 first exons with individual promoter elements are tandemly arrayed upstream of 4 shared exons so as to synthesize independently as many overlapping primary transcripts. RNA splice sites allow a lead exon to join the common exons to generate mRNAs with unique 5' ends, but common 3' ends. Intra- and interspecies comparisons of amino acid sequences encoded by first exons show an evolutionary continuum; also, recognizable bilirubin- and phenol-specific catalytic units are differentially regulated by model compounds, phenobarbital, and/or aromatic hydrocarbons. Whereas UGT1 loci allow minimal changes to achieve new isozymes, a single deleterious mutation in a common exon negatively impacts the arrangement by inactivating the entire family of isozymes compared to an event at independent loci as seen in the UGT2 family. In humans, lethal hyperbilirubinemic Crigler-Najjar type 1 and milder diseases/syndromes are due to deleterious to mildly deleterious mutations in the bilirubin-specific UGT1A1 or a common exon. In addition, the number of TA repeats (N(5-8)) in the UGT1A1 proximal TATA box affects transcriptional rate and, thus, activity. Evidence also shows that polymorphisms in nonbilirubin-specific first exons also impact chemical detoxifications and other diseases. JF - Methods in enzymology AU - Owens, Ida S AU - Basu, Nikhil K AU - Banerjee, Rajat AD - Section on Genetic Disorders of Drug Metabolism, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 1 EP - 22 VL - 400 SN - 0076-6879, 0076-6879 KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Index Medicus KW - Phylogeny KW - Animals KW - Regulatory Elements, Transcriptional KW - Sequence Homology, Nucleic Acid KW - Multigene Family KW - Humans KW - Crigler-Najjar Syndrome -- genetics KW - Mutation KW - Glucuronosyltransferase -- genetics KW - Glucuronosyltransferase -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69059770?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+enzymology&rft.atitle=UDP-glucuronosyltransferases%3A+gene+structures+of+UGT1+and+UGT2+families.&rft.au=Owens%2C+Ida+S%3BBasu%2C+Nikhil+K%3BBanerjee%2C+Rajat&rft.aulast=Owens&rft.aufirst=Ida&rft.date=2005-01-01&rft.volume=400&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Methods+in+enzymology&rft.issn=00766879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-02-01 N1 - Date created - 2006-01-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pesticides and human cancers. AN - 69043487; 16377589 AB - The potential for human carcinogenicity of almost all pesticides currently on the market has been poorly evaluated and is inadequately understood. Generating mechanistic data in both animal studies and epidemiology will play an increasingly important role in the future. Improved exposure assessment, in large prospective studies that generate reliable exposure-response data that focus on individual pesticide exposures are needed. One of the greatest opportunities to make more rapid progress will be to foster more multi-disciplinary collaborations between toxicologists and epidemiologists. Collaborations on molecular epidemiology investigations offers such opportunities to both toxicologists and epidemiologists that were not possible even a decade ago. JF - Cancer investigation AU - Alavanja, Michael C R AU - Bonner, Matthew R AD - Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA. alavanjm@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 700 EP - 711 VL - 23 IS - 8 SN - 0735-7907, 0735-7907 KW - Carcinogens KW - 0 KW - Pesticides KW - Index Medicus KW - Animals KW - Humans KW - Carcinogens -- chemistry KW - Carcinogens -- toxicity KW - Models, Biological KW - Pesticides -- chemistry KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Pesticides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69043487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigation&rft.atitle=Pesticides+and+human+cancers.&rft.au=Alavanja%2C+Michael+C+R%3BBonner%2C+Matthew+R&rft.aulast=Alavanja&rft.aufirst=Michael+C&rft.date=2005-01-01&rft.volume=23&rft.issue=8&rft.spage=700&rft.isbn=&rft.btitle=&rft.title=Cancer+investigation&rft.issn=07357907&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-01-27 N1 - Date created - 2005-12-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Silicosis and lung cancer: a fifty-year perspective. AN - 68892251; 16350547 AB - The development of our studies on silica carcinogenesis and its mechanisms is reviewed. Starting from an analysis of the cellular reactions to silica in the pathogenesis of silicosis in the rat, followed by an analysis of the carcinogenic response to silica in the lungs of rats (but not in mice and hamsters), we went on to develop cellular models for culture and neoplastic transformation of rat alveolar epithelial cells. We studied the binding of silica to DNA, the generation of reactive oxygen species and the DNA damage mediated by hydroxyl radicals, showing marked differences among silica samples of varying purity. Then we investigated the role of peptides induced by silica in various cells, including cytokines and growth factors. Tumor necrosis factor (TNF)-alpha, which can cause activation of DNA transcription and is required for silica-induced fibrosis, was found to inhibit neoplastic transformation by quartz in cell cultures. Transforming growth factor (TGF)-beta was found to be produced in hyperplastic alveolar type II cells and to reach fibroblasts, macrophages and the connective tissue matrix adjacent to silicotic granulomas. Neuroendocrine cells and their peptides were found to be increased in alveolar and bronchiolar epithelia of silica lesions in rats, in contrast with mice and hamsters. Expression of adhesion molecules was found to be altered in silica-induced carcinogenesis and epithelial-mesenchymal transition was revealed by mesenchymal markers in the induced carcinomas. Promoter hypermethylation of adhesion genes in the induced carcinomas indicated a role for epigenetic mechanisms. JF - Acta bio-medica : Atenei Parmensis AU - Saffiotti, Umberto AD - Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 30 EP - 37 VL - 76 Suppl 2 SN - 0392-4203, 0392-4203 KW - Cytokines KW - 0 KW - Growth Substances KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Cytokines -- physiology KW - Time Factors KW - Growth Substances -- physiology KW - Cell Transformation, Neoplastic KW - Lung Neoplasms -- etiology KW - Silicosis -- pathology KW - Silicosis -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68892251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+bio-medica+%3A+Atenei+Parmensis&rft.atitle=Silicosis+and+lung+cancer%3A+a+fifty-year+perspective.&rft.au=Saffiotti%2C+Umberto&rft.aulast=Saffiotti&rft.aufirst=Umberto&rft.date=2005-01-01&rft.volume=76+Suppl+2&rft.issue=&rft.spage=30&rft.isbn=&rft.btitle=&rft.title=Acta+bio-medica+%3A+Atenei+Parmensis&rft.issn=03924203&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-03-07 N1 - Date created - 2005-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple involvement of oxidative stress in Werner syndrome phenotype. AN - 68875632; 16333757 AB - Werner syndrome is a genetic disease characterized by early ageing, excess cancer risk, high incidence of type II diabetes mellitus, early atherosclerosis, ocular cataracts, and osteoporosis. The protein encoded by the defective gene, WRN (WRNp) associates with three activities, that is, a RecQ DNA helicase, 3'-5'-exonuclease and ATPase activities. By highlighting the DNA helicase activity, a widespread consensus in WS-associated defect(s) has been established, pointing toward a deficiency in maintaining DNA integrity. However, a possible involvement of redox pathways in WS may be suggested by several lines of evidence that include: (i) the multiple functions and interactions of WRNp with oxidative stress-related activities and factors; (ii) the pleiotropic WS clinical phenotype encompassing a number of oxidative stress-related pathologies; (iii) redox-related toxicity mechanisms of several xenobiotics exerting excess toxicity in WS cells; (iv) recent in vivo and in vitro findings of redox abnormalities in WS patients and in WS cells. The working hypothesis is raised that a deficiency in WRNp, and the pleiotropic clinical phenotype in WS patients may provide the basis to envision an underlying in vivo prooxidant state, which causes oxidative damage to biomolecules, with multiple oxidative stress-related alterations, resulting in multi-faceted clinical consequences. JF - Biogerontology AU - Pagano, Giovanni AU - Zatterale, Adriana AU - Degan, Paolo AU - d'Ischia, Marco AU - Kelly, Frank J AU - Pallardó, Federico V AU - Kodama, Seiji AD - Italian National Cancer Institute, G. Pascale Foundation, I-80131 Naples, Italy. gbpagano@tin.it Y1 - 2005 PY - 2005 DA - 2005 SP - 233 EP - 243 VL - 6 IS - 4 SN - 1389-5729, 1389-5729 KW - Xenobiotics KW - 0 KW - Index Medicus KW - Phenotype KW - Humans KW - Xenobiotics -- pharmacology KW - Werner Syndrome -- metabolism KW - Oxidative Stress UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68875632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biogerontology&rft.atitle=Multiple+involvement+of+oxidative+stress+in+Werner+syndrome+phenotype.&rft.au=Pagano%2C+Giovanni%3BZatterale%2C+Adriana%3BDegan%2C+Paolo%3Bd%27Ischia%2C+Marco%3BKelly%2C+Frank+J%3BPallard%C3%B3%2C+Federico+V%3BKodama%2C+Seiji&rft.aulast=Pagano&rft.aufirst=Giovanni&rft.date=2005-01-01&rft.volume=6&rft.issue=4&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Biogerontology&rft.issn=13895729&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-06-19 N1 - Date created - 2005-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas. AN - 68845150; 16316942 AB - Chemical carcinogens induce both benign and malignant mammary gland tumors in female Sprague-Dawley rats. To identify gene expression profiles associated with malignancy, cDNA microarray analysis was used to compare gene expression profiles in rat mammary gland carcinomas, adenomas, and normal mammary gland. Tumors were induced with various chemical carcinogens including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 7-12-dimethylbenz[a]anthracene (DMBA), N-nitrosomethylurea (NMU), and 4-aminobiphenyl. The global gene expression profiles in carcinomas and adenomas were distinguishable by hierarchical clustering and multi-dimensional scaling analyses. Permutation analysis revealed 110 clones statistically differentially expressed between benign and malignant tumors (p < 0.0005). Carcinomas showed relatively high expression of several genes associated with mammary epithelial cell growth and proliferation (e.g., cyclin D1, PDGFalpha) and relatively low expression of differentiation marker genes (e.g., beta -casein, whey acidic protein, transferrin). Other categories of genes showing differential expression between carcinomas and adenomas were associated with protein homeostasis, cytoskeleton, extracellular matrix, and cell metabolism (fatty acid metabolism, oxidative phosphorylation, and glycolysis). Major gene families implicated in malignancy by over-expression in carcinomas included the annexins (annexin A1 and A4) and Stat family of transcription factors (Stat3 and Stat5a). The elevated expression of the prolactin receptor in carcinomas concomitant with several components of the mitogenic prolactin signaling pathway implicated prolactin/prolactin receptor/Stat5a/cyclin D1 in rat mammary gland malignancy. JF - Toxicologic pathology 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, Bethesda, Maryland, 20892-4262, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 768 EP - 775 VL - 33 IS - 7 SN - 0192-6233, 0192-6233 KW - DNA, Complementary KW - 0 KW - Index Medicus KW - Rats KW - Signal Transduction -- physiology KW - Gene Expression Profiling KW - Animals KW - Rats, Sprague-Dawley KW - In Situ Hybridization KW - DNA, Complementary -- genetics KW - Oligonucleotide Array Sequence Analysis KW - Reverse Transcriptase Polymerase Chain Reaction KW - Female KW - DNA, Complementary -- biosynthesis KW - Mammary Neoplasms, Experimental -- chemically induced KW - Carcinoma -- pathology KW - Adenoma -- chemically induced KW - Mammary Neoplasms, Experimental -- genetics KW - Adenoma -- pathology KW - Adenoma -- genetics KW - Mammary Neoplasms, Experimental -- pathology KW - Gene Expression Regulation, Neoplastic -- genetics KW - Carcinoma -- genetics KW - Carcinoma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68845150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Global+gene+expression+profiling+of+chemically+induced+rat+mammary+gland+carcinomas+and+adenomas.&rft.au=Shan%2C+Liang%3BYu%2C+Minshu%3BSnyderwine%2C+Elizabeth+G&rft.aulast=Shan&rft.aufirst=Liang&rft.date=2005-01-01&rft.volume=33&rft.issue=7&rft.spage=768&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 - 2006-01-20 N1 - Date created - 2005-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paclitaxel plus ifosfamide and cisplatin in second-line treatment of germ cell tumors: a phase II study. AN - 68796644; 16284696 AB - The aim of this study was to determine efficacy and toxicity of TIP combination (paclitaxel, ifosfamid, cisplatin) as first salvage treatment in patients with relapsed germ cell tumours (GCTs). Excellent results were achieved from TIP combination with a dose 250 mg/m(2) of paclitaxel [5]. Our hypothesis was that comparable efficacy with less toxicity could be achieved even with a lower dose of 175 mg/m(2) paclitaxel in TIP. In 17 consecutive patients with failed standard 1st line treatment, we used four to six courses of paclitaxel 175 mg/m(2) on day 1 and ifosfamide 1,200 mg/m(2) plus cisplatin 20 mg/m(2), both on day 1 through 5, every 3 weeks. Eleven patients achieved favorable response (65%; 95% confidence interval, 42 to 87%) with 7 complete responses (41%). Estimated 2-year disease free survival is 47% (95% CI, 23-71%). Treatment combination was well tolerated and myelosupression was major toxicity. Granulocytopenia Gr3-4 was observed in 8% and febrile neutropenia in 7% of the courses. No case of severe neurotoxicity or treatment-related death was observed. In our study, TIP combination had good toxicity profile. The results however, did not show expected treatment efficacy and we raise the idea of paclitaxel dosage relevance in TIP. JF - Neoplasma AU - Mardiak, J AU - Sálek, T AU - Sycová-Milá, Z AU - Obertová, J AU - Hlavatá, Z AU - Mego, M AU - Recková, M AU - Koza, I AD - Department of Medical Oncology, National Cancer Institute, 833 10 Bratislava, Slovak Republic. jozef.mardiak@nou.sk Y1 - 2005 PY - 2005 DA - 2005 SP - 497 EP - 501 VL - 52 IS - 6 SN - 0028-2685, 0028-2685 KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Ifosfamide KW - UM20QQM95Y KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Humans KW - Mediastinal Neoplasms -- drug therapy KW - Retroperitoneal Neoplasms -- drug therapy KW - Prognosis KW - Mediastinal Neoplasms -- pathology KW - Cisplatin -- administration & dosage KW - Prospective Studies KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Maximum Tolerated Dose KW - Retroperitoneal Neoplasms -- pathology KW - Neoplasms, Gonadal Tissue -- drug therapy KW - Neoplasms, Gonadal Tissue -- pathology KW - Male KW - Ifosfamide -- administration & dosage KW - Testicular Neoplasms -- drug therapy KW - Neoplasm Recurrence, Local -- drug therapy KW - Testicular Neoplasms -- pathology KW - Salvage Therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Germinoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Germinoma -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68796644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Paclitaxel+plus+ifosfamide+and+cisplatin+in+second-line+treatment+of+germ+cell+tumors%3A+a+phase+II+study.&rft.au=Mardiak%2C+J%3BS%C3%A1lek%2C+T%3BSycov%C3%A1-Mil%C3%A1%2C+Z%3BObertov%C3%A1%2C+J%3BHlavat%C3%A1%2C+Z%3BMego%2C+M%3BReckov%C3%A1%2C+M%3BKoza%2C+I&rft.aulast=Mardiak&rft.aufirst=J&rft.date=2005-01-01&rft.volume=52&rft.issue=6&rft.spage=497&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-02-14 N1 - Date created - 2005-11-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of dietary supplements on aspirin and other antiplatelet agents: an evidence-based approach. AN - 68771181; 16115664 JF - Thrombosis research AU - Desai, Ditina AU - Hasan, Ahmed AU - Wesley, Robert AU - Sunderland, Edwin AU - Pucino, Frank AU - Csako, Gyorgy AD - Pharmacy Department, Clinical Center, National Institutes of Health, DHHS, Bldg 10, Room 1N-257, Bethesda, MD 20892-1196, USA. ravald@cc.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 87 EP - 101; discussion 113-5 VL - 117 IS - 1-2 SN - 0049-3848, 0049-3848 KW - Platelet Aggregation Inhibitors KW - 0 KW - Aspirin KW - R16CO5Y76E KW - Index Medicus KW - Risk Factors KW - Humans KW - Prevalence KW - Clinical Trials as Topic -- statistics & numerical data KW - Thrombosis -- prevention & control KW - Drug Interactions KW - Platelet Aggregation Inhibitors -- therapeutic use KW - Dietary Supplements -- statistics & numerical data KW - Evidence-Based Medicine -- methods KW - Aspirin -- therapeutic use KW - Thrombosis -- epidemiology KW - Risk Assessment -- methods KW - Thrombosis -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68771181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Thrombosis+research&rft.atitle=Effects+of+dietary+supplements+on+aspirin+and+other+antiplatelet+agents%3A+an+evidence-based+approach.&rft.au=Desai%2C+Ditina%3BHasan%2C+Ahmed%3BWesley%2C+Robert%3BSunderland%2C+Edwin%3BPucino%2C+Frank%3BCsako%2C+Gyorgy&rft.aulast=Desai&rft.aufirst=Ditina&rft.date=2005-01-01&rft.volume=117&rft.issue=1-2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Thrombosis+research&rft.issn=00493848&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-01-05 N1 - Date created - 2005-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dialogue with patient care organizations. AN - 68771178; 16125754 JF - Thrombosis research AU - Costello, Rebecca AU - Young, Joan AU - Burkholder, Rebecca AU - Cranston, Joseph AU - Ortel, Thomas L AU - Dentali, Steven AU - Cotter, Richard AU - O'sullivan Maillet, Julie AU - Hawkins, Bruce AU - Craig Hooper, W AD - Office of Dietary Supplements, National Institutes of Health Bethesda, MD 20892, USA. CostellB@od.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 211 EP - 22; discussion 223-5 VL - 117 IS - 1-2 SN - 0049-3848, 0049-3848 KW - Fibrinolytic Agents KW - 0 KW - Index Medicus KW - Humans KW - Drug Interactions KW - Consumer Product Safety KW - Product Labeling KW - Drug-Related Side Effects and Adverse Reactions KW - Fibrinolytic Agents -- adverse effects KW - Dietary Supplements -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68771178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Thrombosis+research&rft.atitle=Dialogue+with+patient+care+organizations.&rft.au=Costello%2C+Rebecca%3BYoung%2C+Joan%3BBurkholder%2C+Rebecca%3BCranston%2C+Joseph%3BOrtel%2C+Thomas+L%3BDentali%2C+Steven%3BCotter%2C+Richard%3BO%27sullivan+Maillet%2C+Julie%3BHawkins%2C+Bruce%3BCraig+Hooper%2C+W&rft.aulast=Costello&rft.aufirst=Rebecca&rft.date=2005-01-01&rft.volume=117&rft.issue=1-2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Thrombosis+research&rft.issn=00493848&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-01-05 N1 - Date created - 2005-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conference summary and recommendations for research. AN - 68769825; 16225912 JF - Thrombosis research AU - Hasan, Ahmed A K AU - Marder, Victor J AD - Thrombosis and Hemostasis Program, Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute, National Institutes of Health Bethesda, MD 20892, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 229 EP - 230 VL - 117 IS - 1-2 SN - 0049-3848, 0049-3848 KW - Fibrinolytic Agents KW - 0 KW - Index Medicus KW - Information Dissemination -- methods KW - Research -- organization & administration KW - Herbal Medicine -- methods KW - Drug Interactions KW - Fibrinolytic Agents -- adverse effects KW - Dietary Supplements -- adverse effects KW - Research Design UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68769825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Thrombosis+research&rft.atitle=Conference+summary+and+recommendations+for+research.&rft.au=Hasan%2C+Ahmed+A+K%3BMarder%2C+Victor+J&rft.aulast=Hasan&rft.aufirst=Ahmed+A&rft.date=2005-01-01&rft.volume=117&rft.issue=1-2&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Thrombosis+research&rft.issn=00493848&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-01-05 N1 - Date created - 2005-11-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The molecular signature of metastases of human hepatocellular carcinoma. AN - 68668020; 16210873 AB - The current metastasis paradigm suggests that the primary tumor starts off benign but over time slowly acquires changes that provide a few rare cells within the tumor the ability to metastasize. However, this concept has been challenged by several recent studies using the microarray-based approach. We have recently found that the molecular signature of primary hepatocellular carcinoma (HCC) is very similar to that of their corresponding metastases, while it differs significantly in primary HCCs with or without metastasis. Similar findings are also evident in primary cancers of the lung, breast, and prostate. Such a signature can be used to predict the prognosis of HCC patients. Moreover, there are significant differences in the gene expression profiles of liver parenchyma among HCC patients with or without intrahepatic metastases. These findings imply that many of the metastasis-promoting genes are embedded in the primary tumors and that the ability to metastasize may be an inherent quality of the tumor from the beginning. In addition, the condition of liver parenchyma may dictate the intrahepatic metastasis potential, which is consistent with the hypothesis that the degree of viral-hepatitis-mediated liver damage or possibly the genetic makeup of individuals may play an important role in metastasis. JF - Oncology AU - Budhu, Anuradha S AU - Zipser, Brian AU - Forgues, Marshonna AU - Ye, Qing-Hai AU - Sun, Zongtang AU - Wang, Xin W AD - Liver Carcinogenesis Group, LHC, CCR, NCI, NIH, Bethesda, MD 20892, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 23 EP - 27 VL - 69 Suppl 1 SN - 0030-2414, 0030-2414 KW - Biomarkers, Tumor KW - 0 KW - SPP1 protein, human KW - Sialoglycoproteins KW - Osteopontin KW - 106441-73-0 KW - Index Medicus KW - Sialoglycoproteins -- physiology KW - Gene Expression Profiling KW - Biomarkers, Tumor -- genetics KW - Humans KW - Prognosis KW - Biomarkers, Tumor -- analysis KW - Sialoglycoproteins -- analysis KW - Models, Biological KW - Liver Neoplasms -- pathology KW - Neoplasm Metastasis -- genetics KW - Carcinoma, Hepatocellular -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68668020?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology&rft.atitle=The+molecular+signature+of+metastases+of+human+hepatocellular+carcinoma.&rft.au=Budhu%2C+Anuradha+S%3BZipser%2C+Brian%3BForgues%2C+Marshonna%3BYe%2C+Qing-Hai%3BSun%2C+Zongtang%3BWang%2C+Xin+W&rft.aulast=Budhu&rft.aufirst=Anuradha&rft.date=2005-01-01&rft.volume=69+Suppl+1&rft.issue=&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Oncology&rft.issn=00302414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-11-07 N1 - Date created - 2005-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Triplex targeted genomic crosslinks enter separable deletion and base substitution pathways. AN - 68625629; 16186129 AB - We have synthesized triple helix forming oligonucleotides (TFOs) that target a psoralen (pso) interstrand crosslink to a specific chromosomal site in mammalian cells. Mutagenesis of the targeted crosslinks results in base substitutions and deletions. Identification of the gene products involved in mutation formation is important for developing practical applications of pso-TFOs, and may be informative about the metabolism of other interstrand crosslinks. We have studied mutagenesis of a pso-TFO genomic crosslink in repair proficient and deficient cells. Deficiencies in non homologous end joining and mismatch repair do not influence mutation patterns. In contrast, the frequency of base substitutions is dependent on the activity of ERCC1/XPF and polymerase zeta, but independent of other nucleotide excision repair (NER) or transcription coupled repair (TCR) genes. In NER/TCR deficient cells the frequency of deletions rises, indicating that in wild-type cells NER/TCR functions divert pso-TFO crosslinks from processes that result in deletions. We conclude that targeted pso-TFO crosslinks can enter genetically distinct mutational routes that resolve to base substitutions or deletions. JF - Nucleic acids research AU - Richards, Sally AU - Liu, Su-Ting AU - Majumdar, Alokes AU - Liu, Ji-Lan AU - Nairn, Rodney S AU - Bernier, Michel AU - Maher, Veronica AU - Seidman, Michael M AD - Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr, Baltimore, MD 21224, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 5382 EP - 5393 VL - 33 IS - 17 KW - Cross-Linking Reagents KW - 0 KW - DNA-Binding Proteins KW - Oligonucleotides KW - triplex DNA KW - xeroderma pigmentosum group F protein KW - DNA KW - 9007-49-2 KW - Hypoxanthine Phosphoribosyltransferase KW - EC 2.4.2.8 KW - DNA polymerase zeta KW - EC 2.7.7.- KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Ficusin KW - KTZ7ZCN2EX KW - Index Medicus KW - Animals KW - DNA Repair KW - Hypoxanthine Phosphoribosyltransferase -- genetics KW - Cricetulus KW - Humans KW - Ficusin -- pharmacology KW - Base Sequence KW - CHO Cells KW - DNA -- chemistry KW - DNA-Binding Proteins -- physiology KW - G1 Phase KW - Mutation KW - Genomics KW - Cricetinae KW - DNA-Directed DNA Polymerase -- metabolism KW - Oligonucleotides -- chemistry KW - Sequence Deletion KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68625629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Triplex+targeted+genomic+crosslinks+enter+separable+deletion+and+base+substitution+pathways.&rft.au=Richards%2C+Sally%3BLiu%2C+Su-Ting%3BMajumdar%2C+Alokes%3BLiu%2C+Ji-Lan%3BNairn%2C+Rodney+S%3BBernier%2C+Michel%3BMaher%2C+Veronica%3BSeidman%2C+Michael+M&rft.aulast=Richards&rft.aufirst=Sally&rft.date=2005-01-01&rft.volume=33&rft.issue=17&rft.spage=5382&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 - 2005-10-13 N1 - Date created - 2005-09-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 2005 Feb 11;280(6):4722-9 [15548521] Mol Cell Biol. 2005 Mar;25(6):2297-309 [15743825] DNA Repair (Amst). 2005 May 2;4(5):594-605 [15811631] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2941-6 [8610147] Science. 1996 Feb 9;271(5250):802-5 [8628995] J Biol Chem. 2001 Aug 3;276(31):28991-8 [11389147] Mol Cell. 2001 Jul;8(1):7-8 [11515498] Mutat Res. 2001 Dec 19;487(3-4):73-83 [11738934] Mol Cell. 2001 Dec;8(6):1163-74 [11779493] Mol Cell Biol. 2002 Apr;22(7):2388-97 [11884621] Lancet Oncol. 2001 Aug;2(8):483-90 [11905724] J Cell Biochem. 2002;85(2):346-56 [11948690] Biochemistry. 2002 Jun 18;41(24):7716-24 [12056903] Mutat Res. 2002 Dec 29;510(1-2):71-80 [12459444] Mol Cell Biol. 2003 Jan;23(2):754-61 [12509472] J Biol Chem. 2003 Feb 14;278(7):5250-4 [12473662] J Biol Chem. 2003 Mar 28;278(13):11072-7 [12538585] J Clin Invest. 2003 Aug;112(4):487-94 [12925687] Mutat Res. 2003 Nov 27;532(1-2):103-15 [14643432] Mol Cell Biol. 2004 Jan;24(1):123-34 [14673148] Biochemistry. 2004 Feb 10;43(5):1343-51 [14756571] Nucleic Acids Res. 2004;32(3):1143-53 [14966263] Mol Cell Biol. 2000 Nov;20(21):8283-9 [11027296] Science. 2000 Oct 20;290(5491):530-3 [11039937] Mol Cell Biol. 2001 Feb;21(3):713-20 [11154259] Cell. 2001 Apr 20;105(2):177-86 [11336668] FASEB J. 2001 May;15(7):1224-6 [11344095] Mol Cell Biol. 2004 Jul;24(13):5776-87 [15199134] J Biol Chem. 2004 Aug 27;279(35):36462-9 [15213235] Proc Natl Acad Sci U S A. 1973 Apr;70(4):1064-8 [4577788] J Mol Biol. 1976 May 5;103(1):39-59 [785009] Mutat Res. 1978 Dec;52(3):409-20 [723911] Cell. 1983 Jun;33(2):405-12 [6305508] Cancer Res. 1985 Apr;45(4):1737-43 [3919945] J Biol Chem. 1989 Apr 25;264(12):6755-65 [2708342] Proc Natl Acad Sci U S A. 1989 Jun;86(11):3982-6 [2657732] Exp Cell Res. 1990 Mar;187(1):4-10 [2298260] J Cell Biochem. 1990 Jun;43(2):173-83 [2380262] Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5602-6 [2062839] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7879-83 [8356097] Carcinogenesis. 1994 Feb;15(2):201-7 [8313509] Biochemistry. 1994 Sep 6;33(35):10794-9 [8075081] Mol Cell Biol. 1995 Mar;15(3):1759-68 [7862165] Mol Cell Biol. 1995 Jul;15(7):3722-30 [7791779] J Biol Chem. 1995 Sep 22;270(38):22595-601 [7673252] J Mol Biol. 1995 Nov 17;254(1):38-49 [7473757] Curr Med Chem. 2000 Jan;7(1):17-37 [10637355] Hum Mol Genet. 2000 Feb 12;9(3):403-11 [10655550] Mol Cell Biol. 2000 Apr;20(7):2446-54 [10713168] Mol Cell Biol. 2000 May;20(10):3425-33 [10779332] Genes Dev. 2000 Apr 15;14(8):907-12 [10783163] J Biol Chem. 2000 Aug 25;275(34):26632-6 [10882712] Mol Cell Biol. 2000 Nov;20(21):7980-90 [11027268] Cancer Chemother Pharmacol. 1996;38(5):406-16 [8765433] Cell. 1996 Sep 6;86(5):811-22 [8797827] J Biol Chem. 1997 Feb 7;272(6):3833-7 [9013642] Biochemistry. 1997 Mar 25;36(12):3506-13 [9132000] Mutagenesis. 1997 Jul;12(4):277-83 [9237774] Somat Cell Mol Genet. 1997 Mar;23(2):97-109 [9330638] Mol Cell Biol. 1997 Dec;17(12):6822-30 [9372913] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6876-80 [9618506] Nat Genet. 1998 Oct;20(2):212-4 [9771719] J Mol Biol. 1999 Mar 12;286(5):1379-87 [10064704] Carcinogenesis. 1999 Feb;20(2):215-20 [10069456] J Bacteriol. 1999 May;181(9):2878-82 [10217781] Mol Cell Biol. 1999 Aug;19(8):5619-30 [10409751] Methods Mol Biol. 1999;113:453-63 [10443442] Electrophoresis. 1999 Jul;20(10):2133-8 [10451126] Biochemistry. 1999 Sep 28;38(39):12850-9 [10504255] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Topical application of representative multifunctional acrylates produced proliferative and inflammatory lesions in F344/N rats and B6C3F1 mice, and squamous cell neoplasms in Tg.AC mice. AN - 68617098; 16176922 AB - Widespread human exposure to multifunctional acrylates is of concern, due to their inherent reactivity and irritating properties. Trimethylolpropane triacrylate (TMPTA) and pentaerythritol triacrylate (PETA) are industrially important representatives of multifunctional acrylates. The current studies characterized the toxicity of 3-month topical administration of technical grade TMPTA and PETA in F344/N rats and B6C3F1 mice, and evaluated the carcinogenic potential of TMPTA and PETA in hemizygous Tg.AC (v-Ha-ras) transgenic mice. Administration of 0.75, 1.5, 3, 6, and 12 mg/kg TMPTA and PETA for 3 months resulted in hyperplastic, degenerative, and necrotic lesions, accompanied by chronic inflammation of the skin, with severities generally increasing with dose. Lesions were slightly more severe in rats, when compared with mice, and illustrate the irritant potential of TMPTA and PETA. A similar dosage regimen was used for the 6-month study with Tg.AC mice. Topical application of TMPTA and PETA to Tg.AC mice showed dose-dependent increases in squamous cell papillomas at the site of application, with decreases in the latency of their appearance in mice receiving 3 mg/kg or greater. Papillomas, the reporter phenotype in Tg.AC mice, were accompanied by a few squamous cell carcinomas, along with hyperplastic and inflammatory lesions. Although chronic inflammation might have contributed to the development of the skin lesions, the dose-related nature of the induction of the skin papillomas in Tg.AC mice by TMPTA and PETA may reflect a potential for carcinogenicity. JF - Toxicologic pathology AU - Doi, Adriana M AU - Hailey, James R AU - Hejtmancik, Milton AU - Toft, John D AU - Vallant, Molly AU - Chhabra, Rajendra S AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 631 EP - 640 VL - 33 IS - 6 SN - 0192-6233, 0192-6233 KW - Acrylates KW - 0 KW - Propylene Glycols KW - trimethylolpropane triacrylate KW - 4B67KGL96S KW - pentaerythrityl triacrylate KW - PJJ1161ULF KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Sex Factors KW - Dose-Response Relationship, Drug KW - Skin -- pathology KW - Mice KW - Mice, Transgenic KW - Inflammation KW - Rats KW - Genes, ras KW - Rats, Inbred F344 KW - Necrosis KW - Epidermis -- drug effects KW - Hyperplasia KW - Skin -- drug effects KW - Liver -- drug effects KW - Carcinogenicity Tests KW - Epidermis -- pathology KW - Time Factors KW - Male KW - Administration, Topical KW - Female KW - Stomach Neoplasms -- pathology KW - Papilloma -- pathology KW - Skin Neoplasms -- pathology KW - Acrylates -- toxicity KW - Papilloma -- genetics KW - Precancerous Conditions -- pathology KW - Propylene Glycols -- administration & dosage KW - Skin Neoplasms -- genetics KW - Precancerous Conditions -- genetics KW - Stomach Neoplasms -- chemically induced KW - Stomach Neoplasms -- genetics KW - Precancerous Conditions -- chemically induced KW - Propylene Glycols -- toxicity KW - Skin Neoplasms -- chemically induced KW - Acrylates -- administration & dosage KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68617098?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Topical+application+of+representative+multifunctional+acrylates+produced+proliferative+and+inflammatory+lesions+in+F344%2FN+rats+and+B6C3F1+mice%2C+and+squamous+cell+neoplasms+in+Tg.AC+mice.&rft.au=Doi%2C+Adriana+M%3BHailey%2C+James+R%3BHejtmancik%2C+Milton%3BToft%2C+John+D%3BVallant%2C+Molly%3BChhabra%2C+Rajendra+S&rft.aulast=Doi&rft.aufirst=Adriana&rft.date=2005-01-01&rft.volume=33&rft.issue=6&rft.spage=631&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 - 2006-01-23 N1 - Date created - 2005-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Weekly docetaxel in pretreated metastatic breast cancer patients: a phase I-II study. AN - 68488011; 16020963 AB - We conducted a phase I-II study to determine the maximum tolerated dose (MTD), toxicity and activity of weekly docetaxel administration in pretreated metastatic breast cancer patients. In phase I, cohorts of 3 women with pretreated metastatic breast cancer were treated with a 1-hour infusion of docetaxelat 30, 35, 40 mg/m2/week after premedication with two doses of dexamethazone 8 mg 12 h apart. Subsequently, a cohort of 28 women was treated at the MTD for 24 consecutive weeks in a phase II setting and was assessed for toxicity and activity. Three patients were treated at each of the first two dose levels; 9 patients were treated at the 3rd level (40 mg/m2/week). Dose-limiting toxicities (DLTs) were experienced at that level by 2/6 patients of the first two accrued groups and in 2/3 patients of the 3rd (confirmation) group, thus establishing the subsequent phase II dose at 35 mg/m2/week. Two out of 28 evaluable patients (7.1%, 95% CI 0-16.7) showed complete responses, whereas 8 (28.6%, 95% CI 11.8-45.3) showed partial responses, and an objective response rate of 35.7% (95% confidence interval, CI 18-53.5%). In addition, 8 patients (28.6%) had stable disease. The median time to progression and overall survival were 5 (range 1-15) and 15 months (95% CI 7-23), respectively. One patient experienced 1 episode of grade 3 neutropenia. Severe asthenia was the main reason for interruption of chemotherapy (10 patients, 35.5%). In pretreated metastatic breast cancer patients, the sustained weekly administration of docetaxel, even though it demonstrated an activity similar to a 3-weekly schedule could not be maintained for the planned 24 weeks due to the progressive emergence of nonhematological side effects that approached DLTs. (c) 2005 S. Karger AG, Basel JF - Oncology AU - Nisticò, Cecilia AU - Cognetti, Francesco AU - Frontini, Luciano AU - Barni, Sandro AU - Ferretti, Gianluigi AU - Bria, Emilio AU - Milella, Michele AU - Garufi, Carlo AU - Cuppone, Federica AU - Vanni, Barbara AU - Carlini, Paolo AU - Terzoli, Edmondo AD - Department of Medical Oncology, Regina Elena National Cancer Institute, Roma, Italy. cnistico@ifo.it Y1 - 2005 PY - 2005 DA - 2005 SP - 356 EP - 363 VL - 68 IS - 4-6 SN - 0030-2414, 0030-2414 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Taxoids KW - docetaxel KW - 15H5577CQD KW - Index Medicus KW - Survival Rate KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Maximum Tolerated Dose KW - Adolescent KW - Female KW - Breast Neoplasms -- drug therapy KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Taxoids -- therapeutic use KW - Breast Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68488011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology&rft.atitle=Weekly+docetaxel+in+pretreated+metastatic+breast+cancer+patients%3A+a+phase+I-II+study.&rft.au=Nistic%C3%B2%2C+Cecilia%3BCognetti%2C+Francesco%3BFrontini%2C+Luciano%3BBarni%2C+Sandro%3BFerretti%2C+Gianluigi%3BBria%2C+Emilio%3BMilella%2C+Michele%3BGarufi%2C+Carlo%3BCuppone%2C+Federica%3BVanni%2C+Barbara%3BCarlini%2C+Paolo%3BTerzoli%2C+Edmondo&rft.aulast=Nistic%C3%B2&rft.aufirst=Cecilia&rft.date=2005-01-01&rft.volume=68&rft.issue=4-6&rft.spage=356&rft.isbn=&rft.btitle=&rft.title=Oncology&rft.issn=00302414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-20 N1 - Date created - 2005-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coincident stimulation of convergent cortical inputs enhances immediate early gene induction in the striatum. AN - 68481825; 15978736 AB - The effect of coincident stimulation of convergent corticostriatal inputs was analyzed by the induction of immediate early genes in striatal neurons. Cortical motor areas were stimulated through implanted electrodes in awake, behaving rats, and the induction of the mRNAs encoding the immediate early genes (IEGs) c-fos and arc was analyzed in the striatum with in situ hybridization histochemistry. In the first experiment, unilateral stimulation of the medial agranular cortex, orofacial region of the lateral agranular cortex or the forelimb region of the lateral agranular cortex resulted in IEG induction in the striatum, which was restricted to the topographically related area receiving input from the stimulated cortical area. In a second experiment, stimulation parameters were altered, including frequency, number of pulses/train, and number of trains/s. These parameters did not have a significant effect on IEG induction. Notably, in some cases, in which there was IEG induction not only in the stimulated cortical region, but also in the homologous area in the contralateral hemisphere, very robust IEG induction was observed in the striatum. In a third experiment, the orofacial regions of the lateral agranular cortex of both hemispheres were stimulated coincidently. All of these animals showed robust striatal IEG induction. This IEG induction was attenuated by pretreatment with an NMDA antagonist MK-801. In a fourth experiment, we tested whether the coincidence of bilateral cortical stimulation contributed to the efficacy of striatal IEG induction. Either alternating stimulation or coincident stimulation of non-homologous cortical regions produced significantly lower striatal IEG induction than obtained with coincident stimulation of homologous cortical areas. Enhanced striatal IEG induction occurred in indirect striatal neurons, labeled with enkephalin, but was also present in a large number of enkephalin-negative neurons, most of which are likely direct pathway neurons. These results suggest that regional and temporal convergence of cortical inputs enhances striatal IEG induction. JF - Neuroscience AU - Miyachi, S AU - Hasegawa, Y T AU - Gerfen, C R AD - Section on Neuroanatomy, Laboratory of Systems Neuroscience, National Institute of Mental Health, Building 35, Room 3A-1000, 35 Convent Drive, Bethesda, MD 20892, USA. miyachi@tmin.ac.jp Y1 - 2005 PY - 2005 DA - 2005 SP - 1013 EP - 1022 VL - 134 IS - 3 SN - 0306-4522, 0306-4522 KW - Enkephalins KW - 0 KW - Excitatory Amino Acid Antagonists KW - RNA, Messenger KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Index Medicus KW - AIDS-Related Complex -- genetics KW - Animals KW - Electric Stimulation -- methods KW - Enkephalins -- genetics KW - Genes, fos -- genetics KW - Dose-Response Relationship, Radiation KW - Dizocilpine Maleate -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - RNA, Messenger -- metabolism KW - In Situ Hybridization -- methods KW - Functional Laterality KW - Male KW - Gene Expression -- drug effects KW - Corpus Striatum -- metabolism KW - Genes, Immediate-Early -- genetics KW - Motor Cortex -- radiation effects KW - Motor Cortex -- drug effects KW - Gene Expression -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68481825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Coincident+stimulation+of+convergent+cortical+inputs+enhances+immediate+early+gene+induction+in+the+striatum.&rft.au=Miyachi%2C+S%3BHasegawa%2C+Y+T%3BGerfen%2C+C+R&rft.aulast=Miyachi&rft.aufirst=S&rft.date=2005-01-01&rft.volume=134&rft.issue=3&rft.spage=1013&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-11-14 N1 - Date created - 2005-08-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA drug design for cancer therapy. AN - 68481706; 16101439 AB - DNA (antisense and other oligonucleotides) drug design represents a direct genetic approach for cancer treatment. Such an approach takes advantage of mechanisms that activate genes known to confer a growth advantage to neoplastic cells. The ability to block the expression of these genes allows exploration of normal growth regulation. Progress in DNA drug technology has been rapid, and the traditional antisense inhibition of gene expression is now viewed on a genomic scale. This global view has led to a new vision in antisense technology, the elimination of nonspecific and undesirable side effects, and ultimately the generation of more effective and less toxic nucleic acid medicines. Several antisense oligonucleotides are in clinical trials, are well tolerated, and are potentially active therapeutically. DNA drugs are promising molecular medicines for treating human cancer in the near future. JF - Current pharmaceutical design AU - Cho-Chung, Y S AD - BRL, CCR, National Cancer Institute, Bethesda, MD 20892-1750, USA. yc12b@nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 2811 EP - 2823 VL - 11 IS - 22 SN - 1381-6128, 1381-6128 KW - Antineoplastic Agents KW - 0 KW - Oligonucleotides KW - Oligonucleotides, Antisense KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Oligonucleotides -- pharmacology KW - Combined Modality Therapy KW - Humans KW - Clinical Trials as Topic KW - Molecular Mimicry KW - Oligonucleotides, Antisense -- pharmacology KW - Genetic Therapy KW - Oligonucleotides, Antisense -- chemical synthesis KW - Oligonucleotides -- chemical synthesis KW - DNA -- chemistry KW - Antineoplastic Agents -- chemical synthesis KW - Drug Design KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68481706?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+pharmaceutical+design&rft.atitle=DNA+drug+design+for+cancer+therapy.&rft.au=Cho-Chung%2C+Y+S&rft.aulast=Cho-Chung&rft.aufirst=Y&rft.date=2005-01-01&rft.volume=11&rft.issue=22&rft.spage=2811&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-08 N1 - Date created - 2005-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Beyond single pathway inhibition: MEK inhibitors as a platform for the development of pharmacological combinations with synergistic anti-leukemic effects. AN - 68481661; 16101455 AB - The MEK/MAPK signaling module is a key integration point along signal transduction cascades that regulate cell growth, survival, and differentiation, and is aberrantly activated in many human tumors. In tumor cells, constitutive MAPK activation affords increased proliferation and resistance to apoptotic stimuli, including classical cytotoxic drugs. In most instances, however, MAPK inhibition has cytostatic rather than cytotoxic effects, which may explain the lack of objective responses observed in early clinical trials of MEK inhibitors. Nevertheless, amenability of the MAPK pathway to pharmacodynamic evaluation and negligible clinical toxicity make MEK inhibitors an ideal platform to build pharmacological combinations with synergistic antitumor activity. In AML, the MEK/MAPK pathway is constitutively activated in the majority of cases (75%), conferring a uniformly poor prognosis; in preclinical models of AML, MEK blockade profoundly inhibits cell growth and proliferation and downregulates the expression of several anti-apoptotic players, thereby lowering the apoptotic threshold. Apoptosis induction, however, requires concentrations of MEK inhibitors much higher than those required to inhibit proliferation. Nevertheless, MEK blockade efficiently and selectively sensitizes leukemic cells to sub-optimal doses of other apoptotic stimuli, including classical cytotoxics (nucleoside analogs, microtubule-targeted drugs, gamma-irradiation), biologicals (retinoids, interferons, arsenic trioxide), and, most interestingly, other signal transduction/apoptosis modulators (UCN-01, STI571, Bcl-2 antagonists). In most instances, these MEK inhibition-based combinations result in a striking pro-apoptotic synergism in preclinical models. Here we briefly discuss evidence suggesting that MAPK pathway inhibition could play a prominent role in the development of integrated therapeutic strategies aimed at synergistic anti-leukemic effects. JF - Current pharmaceutical design AU - Milella, M AU - Precupanu, C M AU - Gregorj, C AU - Ricciardi, M R AU - Petrucci, M T AU - Kornblau, S M AU - Tafuri, A AU - Andreeff, M AD - Division of Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy. milella@ifo.it Y1 - 2005 PY - 2005 DA - 2005 SP - 2779 EP - 2795 VL - 11 IS - 21 SN - 1381-6128, 1381-6128 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - Index Medicus KW - Animals KW - Humans KW - Apoptosis -- drug effects KW - Drug Synergism KW - Leukemia -- drug therapy KW - Leukemia -- radiotherapy KW - Signal Transduction -- drug effects KW - Mitogen-Activated Protein Kinase Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Leukemia -- physiopathology KW - Signal Transduction -- radiation effects KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68481661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+pharmaceutical+design&rft.atitle=Beyond+single+pathway+inhibition%3A+MEK+inhibitors+as+a+platform+for+the+development+of+pharmacological+combinations+with+synergistic+anti-leukemic+effects.&rft.au=Milella%2C+M%3BPrecupanu%2C+C+M%3BGregorj%2C+C%3BRicciardi%2C+M+R%3BPetrucci%2C+M+T%3BKornblau%2C+S+M%3BTafuri%2C+A%3BAndreeff%2C+M&rft.aulast=Milella&rft.aufirst=M&rft.date=2005-01-01&rft.volume=11&rft.issue=21&rft.spage=2779&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-31 N1 - Date created - 2005-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Biweekly docetaxel-irinotecan treatment with filgrastim support is highly active in antracycline-Paclitaxel-refractory breast cancer patients. AN - 68481633; 16020968 AB - To evaluate the feasibility and activity of combination treatment with docetaxel (DTX) and irinotecan (CPT-11), given together every other week, combined with filgrastim support, in anthracycline- and paclitaxel-pretreated breast cancer (BC) patients. Advanced BC patients pretreated with anthracycline- and paclitaxel-based chemotherapy were eligible. DTX (80 mg/m2) and CPT-11 (100 mg/m2) were given biweekly with filgrastim support (300 microg/day on days 4-7). Fifty patients (48 with metastatic and 2 with locally advanced cancer) were enrolled, with a total of 318 cycles being delivered. Thirty-one patients had visceral localizations. All patients had received epirubicin plus paclitaxel, with or without cisplatin, as front-line treatment for advanced disease. Overall, fatigue and diarrhea were the main chemotherapy-related toxicities in this study, being severe in 10 (20%) and 4 (8%) patients. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 18 (36%) and 6 (12%) patients, respectively. Red blood cell transfusions were required in 4 patients. A total of 32 objective responses were registered (overall response rate, ORR = 64%, 95% confidence interval = 49-77%), including 8 complete responses (16%). An additional 8 patients showed stable disease. After a median follow-up of 18 (range 4-29) months, 30 patients were still alive, and 19 were progression free; median progression-free and overall survivals were 10 and 23 months, respectively. Biweekly DTX/CPT-11 with G-CSF support is a well-tolerated and highly effective approach in anthracycline-/paclitaxel-pretreated patients. The very promising ORR and survival outcome observed in this subset of patients with a poor prognosis suggest that this regimen might play a major role in the management of this disease. JF - Oncology AU - Frasci, Giuseppe AU - D'Aiuto, Giuseppe AU - Thomas, Renato AU - Comella, Pasquale AU - Di Bonito, Maurizio AU - Lapenta, Liliana AU - D'Aiuto, Massimiliano AU - Botti, Gerardo AU - Vallone, Paolo AU - De Rosa, Vincenzo AU - D'Aniello, Roberta AU - Giordano, Renato AU - Comella, Giuseppe AD - Division of Medical Oncology A, National Cancer Institute of Naples, Naples, and Department of Surgery, Pagani General Hospital, Salerno, Italy. giuseppefrasci@libero.it Y1 - 2005 PY - 2005 DA - 2005 SP - 391 EP - 397 VL - 68 IS - 4-6 SN - 0030-2414, 0030-2414 KW - Anthracyclines KW - 0 KW - Recombinant Proteins KW - Taxoids KW - irinotecan KW - 0H43101T0J KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - docetaxel KW - 15H5577CQD KW - Paclitaxel KW - P88XT4IS4D KW - Filgrastim KW - PVI5M0M1GW KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Disease-Free Survival KW - Neoplasm Staging KW - Dose-Response Relationship, Drug KW - Humans KW - Salvage Therapy KW - Aged KW - Camptothecin -- administration & dosage KW - Taxoids -- administration & dosage KW - Feasibility Studies KW - Adult KW - Camptothecin -- analogs & derivatives KW - Middle Aged KW - Granulocyte Colony-Stimulating Factor -- administration & dosage KW - Maximum Tolerated Dose KW - Anthracyclines -- administration & dosage KW - Female KW - Breast Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Breast Neoplasms -- secondary UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68481633?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology&rft.atitle=Biweekly+docetaxel-irinotecan+treatment+with+filgrastim+support+is+highly+active+in+antracycline-Paclitaxel-refractory+breast+cancer+patients.&rft.au=Frasci%2C+Giuseppe%3BD%27Aiuto%2C+Giuseppe%3BThomas%2C+Renato%3BComella%2C+Pasquale%3BDi+Bonito%2C+Maurizio%3BLapenta%2C+Liliana%3BD%27Aiuto%2C+Massimiliano%3BBotti%2C+Gerardo%3BVallone%2C+Paolo%3BDe+Rosa%2C+Vincenzo%3BD%27Aniello%2C+Roberta%3BGiordano%2C+Renato%3BComella%2C+Giuseppe&rft.aulast=Frasci&rft.aufirst=Giuseppe&rft.date=2005-01-01&rft.volume=68&rft.issue=4-6&rft.spage=391&rft.isbn=&rft.btitle=&rft.title=Oncology&rft.issn=00302414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-20 N1 - Date created - 2005-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intracellular chloride channels: critical mediators of cell viability and potential targets for cancer therapy. AN - 68480213; 16101453 AB - The passage of ions to form and maintain electrochemical gradients is a key element for regulating cellular activities and is dependent on specific channel proteins or complexes. Certain ion channels have been the targets of pharmaceuticals that have had impact on a variety of cardiovascular and neurological diseases. Chloride channels regulate the movement of a major cellular anion, and in so doing they in part determine cell membrane potential, modify transepithelial transport, and maintain intracellular pH and cell volume. There are multiple families of chloride channel proteins, and respiratory, neuromuscular, and renal dysfunction may result from mutations in specific family members. Interest in chloride channels related to cancer first arose when the multidrug resistance protein (MDR/P-glycoprotein) was linked to volume-activated chloride channel activity in cancer cells from patients undergoing chemotherapy. More recently, CLC, CLIC, and CLCA intracellular chloride channels have been recognized for their contributions in modifying cell cycle, apoptosis, cell adhesion, and cell motility. Moreover, advances in structural biology and high-throughput screening provide a platform to identify chemical compounds that modulate the activities of intracellular chloride channels thereby influencing chloride ion transport and altering cell behavior. This review will focus on several chloride channel families that may contribute to the cancer phenotype and suggest how they may serve as novel targets for primary cancer therapy. JF - Current pharmaceutical design AU - Suh, Kwang S AU - Yuspa, Stuart H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 2753 EP - 2764 VL - 11 IS - 21 SN - 1381-6128, 1381-6128 KW - Antineoplastic Agents KW - 0 KW - CFTR protein, human KW - Chloride Channels KW - Chlorides KW - Cystic Fibrosis Transmembrane Conductance Regulator KW - 126880-72-6 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Cell Survival -- drug effects KW - Humans KW - Neoplasms -- physiopathology KW - Molecular Sequence Data KW - Calcium -- physiology KW - Chlorides -- metabolism KW - Amino Acid Sequence KW - Neoplasms -- genetics KW - Cystic Fibrosis Transmembrane Conductance Regulator -- physiology KW - Cell Survival -- physiology KW - Neoplasms -- metabolism KW - Chloride Channels -- classification KW - Chloride Channels -- physiology KW - Chloride Channels -- drug effects KW - Chloride Channels -- genetics KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68480213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+pharmaceutical+design&rft.atitle=Intracellular+chloride+channels%3A+critical+mediators+of+cell+viability+and+potential+targets+for+cancer+therapy.&rft.au=Suh%2C+Kwang+S%3BYuspa%2C+Stuart+H&rft.aulast=Suh&rft.aufirst=Kwang&rft.date=2005-01-01&rft.volume=11&rft.issue=21&rft.spage=2753&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-31 N1 - Date created - 2005-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assignment of murine placental cathepsin R to mouse chromosome bands 13B2-B3 by fluorescence in situ hybridization. AN - 68474480; 16097084 JF - Cytogenetic and genome research AU - Zimonjic, D B AU - Liu, J AU - Xu, W-H AU - Zhou, X AU - Popescu, N C AU - Shi, G P AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 96 VL - 111 IS - 1 KW - DNA Primers KW - 0 KW - ribosomal neutral proteinase KW - Serine Endopeptidases KW - EC 3.4.21.- KW - Index Medicus KW - Animals KW - Base Sequence KW - Chromosome Banding KW - In Situ Hybridization, Fluorescence KW - Mice KW - Chromosomes, Artificial, Bacterial KW - Chromosomes, Mammalian KW - Female KW - Pregnancy KW - Cloning, Molecular KW - Placenta -- enzymology KW - Serine Endopeptidases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68474480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytogenetic+and+genome+research&rft.atitle=Assignment+of+murine+placental+cathepsin+R+to+mouse+chromosome+bands+13B2-B3+by+fluorescence+in+situ+hybridization.&rft.au=Zimonjic%2C+D+B%3BLiu%2C+J%3BXu%2C+W-H%3BZhou%2C+X%3BPopescu%2C+N+C%3BShi%2C+G+P&rft.aulast=Zimonjic&rft.aufirst=D&rft.date=2005-01-01&rft.volume=111&rft.issue=1&rft.spage=96&rft.isbn=&rft.btitle=&rft.title=Cytogenetic+and+genome+research&rft.issn=1424-859X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-11-21 N1 - Date created - 2005-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Respiratory and general health impairments of workers employed in a municipal solid waste disposal at an open landfill site in Delhi. AN - 68442423; 16078639 AB - The objective of this study was to examine the respiratory and general health of workers employed in a municipal solid waste (MSW) disposal at an open landfill site in India. Ninety-six landfill workers of Okhla landfill site, Delhi, and 90 controls matched for age, sex, and socioeconomic conditions were enrolled. Health data was obtained from questionnaire surveys, clinical examination and laboratory investigations. Lung function was evaluated by spirometry. Compared with matched controls, landfill workers had significantly higher prevalences of both upper and lower respiratory symptoms, and they suffered more often from diarrhea, fungal infection and ulceration of the skin, burning sensation in the extremities, tingling or numbness, transient loss of memory, and depression. Spirometry revealed impairment of lung function in 62% of the landfill workers compared to 27% of the controls. Sputum cytology showed squamous metaplasia, abundance of inflammatory cells, alveolar macrophages (AM) and siderophages (macrophages with iron deposits), and high elastase enzyme activity in neutrophils and AM of a majority of landfill workers, indicating adverse cellular lung reaction. Hematological profiles of these workers depicted low hemoglobin and erythrocyte levels with high total leukocyte, eosinophil and monocyte counts. Erythrocytes with target cell morphology were abundant in 42% of the landfill workers compared to 10% of the controls. Toxic granulation in neutrophils, an indication of infection and inflammation, was recorded in 94% of the landfill workers and in 49% of the controls. The results demonstrated higher prevalence of respiratory symptoms, inflammation of the airways, lung function decrement and a wide range of general health problems in MSW disposal workers. JF - International journal of hygiene and environmental health AU - Ray, Manas Ranjan AU - Roychoudhury, Sanghita AU - Mukherjee, Gopeshwar AU - Roy, Senjuti AU - Lahiri, Twisha AD - Experimental Hematology Unit, Chittaranjan National Cancer Institute, Kolkata, India. manasrray@rediffmail.com Y1 - 2005 PY - 2005 DA - 2005 SP - 255 EP - 262 VL - 208 IS - 4 SN - 1438-4639, 1438-4639 KW - Air Pollutants, Occupational KW - 0 KW - Index Medicus KW - India -- epidemiology KW - Hematologic Tests KW - Cities KW - Sputum -- cytology KW - Spirometry KW - Humans KW - Health Surveys KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Male KW - Erythrocytes -- pathology KW - Occupational Exposure KW - Respiratory Tract Diseases -- etiology KW - Health Status KW - Respiratory Tract Diseases -- epidemiology KW - Refuse Disposal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68442423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Respiratory+and+general+health+impairments+of+workers+employed+in+a+municipal+solid+waste+disposal+at+an+open+landfill+site+in+Delhi.&rft.au=Ray%2C+Manas+Ranjan%3BRoychoudhury%2C+Sanghita%3BMukherjee%2C+Gopeshwar%3BRoy%2C+Senjuti%3BLahiri%2C+Twisha&rft.aulast=Ray&rft.aufirst=Manas&rft.date=2005-01-01&rft.volume=208&rft.issue=4&rft.spage=255&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 - 2005-12-20 N1 - Date created - 2005-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Black tea extract can modulate protein expression of H-ras, c-Myc, p53, and Bcl-2 genes during pulmonary hyperplasia, dysplasia, and carcinoma in situ. AN - 68092103; 16050805 AB - Lung cancer has emerged as one of the leading causes of cancer death in most developed and many developing countries of the world. In the absence of effective screening and early detection methods of lung cancer and overall poor prognosis, the 5-year survival following treatment has not improved significantly over the last two decades. It is hoped that the risk of the disease can be minimized by preventive measures. One aspect of lung cancer prevention emphasizes the cessation of tobacco smoking, and another strategy envisages reversal or restriction of the process of lung carcinogenesis by chemopreventive intervention. The latter strategy, however, demands a deeper understanding of the pathogenesis of the disease and the identification of the ideal point of intervention. In the present investigation, we assessed the role of the antioxidant tea components theaflavins (TF) and epigallocatechin gallate (EGCG) for their chemopreventive potential and molecular mechanism of action when administered at the post-initiation phase of lung carcinogenesis in an experimental mouse model. We serially examined the histopathological changes in the lung of mice administered benzo(a)pyrene and correlated them with the frequency of proliferative and apoptotic cells in situ as well as with the expression of H-ras, c-Myc, p53, and Bcl-2 genes, which play key roles in the histopathogenesis of neoplasia. Our findings indicate that both TF and EGCG can influence gene expression to modulate the process of carcinogenesis through the regulation of apoptosis. This results in a lowered incidence and delayed onset of preinvasive lung lesions. JF - Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer AU - Saha, Prosenjit AU - Banerjee, Sarmistha AU - Ganguly, Chaiti AU - Manna, Sugata AU - Panda, Chinmay K AU - Das, Sukta AD - Department of Cancer Chemoprevention, Chittarajan National Cancer Institute, Kolkata, India. Y1 - 2005 PY - 2005 DA - 2005 SP - 211 EP - 224 VL - 24 IS - 3 SN - 0731-8898, 0731-8898 KW - Anticarcinogenic Agents KW - 0 KW - Biflavonoids KW - Plant Extracts KW - Proto-Oncogene Proteins KW - Tea KW - theaflavin KW - 1IA46M0D13 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Catechin KW - 8R1V1STN48 KW - epigallocatechin gallate KW - BQM438CTEL KW - Index Medicus KW - Cell Proliferation -- drug effects KW - Animals KW - Anticarcinogenic Agents -- therapeutic use KW - Catechin -- analogs & derivatives KW - Disease Models, Animal KW - Mice KW - Catechin -- therapeutic use KW - Animals, Newborn KW - Hyperplasia KW - Plant Extracts -- therapeutic use KW - Apoptosis -- drug effects KW - Benzo(a)pyrene -- toxicity KW - Biflavonoids -- therapeutic use KW - Male KW - Female KW - Carcinoma in Situ -- pathology KW - Lung Neoplasms -- prevention & control KW - Proto-Oncogene Proteins -- metabolism KW - Lung -- drug effects KW - Carcinoma in Situ -- genetics KW - Tea -- chemistry KW - Lung -- pathology KW - Lung -- metabolism KW - Carcinoma in Situ -- metabolism KW - Proto-Oncogenes KW - Proto-Oncogene Proteins -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68092103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+pathology%2C+toxicology+and+oncology+%3A+official+organ+of+the+International+Society+for+Environmental+Toxicology+and+Cancer&rft.atitle=Black+tea+extract+can+modulate+protein+expression+of+H-ras%2C+c-Myc%2C+p53%2C+and+Bcl-2+genes+during+pulmonary+hyperplasia%2C+dysplasia%2C+and+carcinoma+in+situ.&rft.au=Saha%2C+Prosenjit%3BBanerjee%2C+Sarmistha%3BGanguly%2C+Chaiti%3BManna%2C+Sugata%3BPanda%2C+Chinmay+K%3BDas%2C+Sukta&rft.aulast=Saha&rft.aufirst=Prosenjit&rft.date=2005-01-01&rft.volume=24&rft.issue=3&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Journal+of+environmental+pathology%2C+toxicology+and+oncology+%3A+official+organ+of+the+International+Society+for+Environmental+Toxicology+and+Cancer&rft.issn=07318898&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-27 N1 - Date created - 2005-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental cardiovascular disease. AN - 68077658; 16046786 AB - The last decade has seen a remarkable growth in the evidence establishing exposure to environmental agents as a risk factor for cardiovascular disease (CVD). Most of this has come from research linking exposure to ambient particulate matter with CVD, although more recent evidence suggests that the ozone might also be contributing factor. Research on the cardiovascular toxicity of other pollutants, notably arsenic, has also grown during this period. In addition to their effects in adults, environmental agents, such as dioxin, have also been shown to adversely affect development of the heart in laboratory animals. Taken together, these results suggest that environmental exposure must be considered as an important risk factor for CVD and that further research to determine mechanisms of action and susceptible populations is needed. This research will require interdisciplinary approaches, and should yield data not only on the toxic effects of pollutants on the cardiovascular system, but on the basic pathophysiology of cardiovascular diseases as well. JF - Cardiovascular toxicology AU - Mastin, J Patrick AD - National Institute of Environmental Health, Research Triangle Park, NC 27709, USA. mastin@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 91 EP - 94 VL - 5 IS - 2 SN - 1530-7905, 1530-7905 KW - Air Pollutants KW - 0 KW - Environmental Pollutants KW - Index Medicus KW - Animals KW - Risk Factors KW - Humans KW - Arteriosclerosis -- pathology KW - Air Pollutants -- adverse effects KW - Cardiovascular Diseases -- etiology KW - Environmental Health KW - Cardiovascular Diseases -- epidemiology KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68077658?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cardiovascular+toxicology&rft.atitle=Environmental+cardiovascular+disease.&rft.au=Mastin%2C+J+Patrick&rft.aulast=Mastin&rft.aufirst=J&rft.date=2005-01-01&rft.volume=5&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Cardiovascular+toxicology&rft.issn=15307905&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-26 N1 - Date created - 2005-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Scorpion venom peptides without disulfide bridges. AN - 68063809; 16036557 AB - Several hundred disulfide-bridged neurotoxic peptides have been characterized from scorpion venom; however, only few scorpion venom peptides without disulfide bridges have been identified and characterized. These non-disulfide-bridged peptides (NDBPs) are a novel class of molecules because of their unique antimicrobial, immunological or cellular signaling activities. This review provides an overview of their structural simplicity, precursor processing, biological activities and evolution, and sheds insight into their potential clinical and agricultural applications. Based on their pharmacological activities and peptide size similarity, we have classified these peptides into six subfamilies. JF - IUBMB life AU - Zeng, Xian-Chun AU - Corzo, Gerardo AU - Hahin, Richard AD - Department of Biotechnology, Key Laboratory of MOE for Virology, Institute of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, P. R. China. zengx@mail.nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 13 EP - 21 VL - 57 IS - 1 SN - 1521-6543, 1521-6543 KW - Anti-Bacterial Agents KW - 0 KW - Immunologic Factors KW - Peptides KW - Scorpion Venoms KW - Bradykinin KW - S8TIM42R2W KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Anti-Bacterial Agents -- metabolism KW - Gene Components KW - Hemolysis -- physiology KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Immunologic Factors -- metabolism KW - Bradykinin -- metabolism KW - Scorpion Venoms -- chemistry KW - Phylogeny KW - Scorpion Venoms -- genetics KW - Scorpions -- chemistry KW - Peptides -- metabolism KW - Peptides -- classification KW - Peptides -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68063809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IUBMB+life&rft.atitle=Scorpion+venom+peptides+without+disulfide+bridges.&rft.au=Zeng%2C+Xian-Chun%3BCorzo%2C+Gerardo%3BHahin%2C+Richard&rft.aulast=Zeng&rft.aufirst=Xian-Chun&rft.date=2005-01-01&rft.volume=57&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=IUBMB+life&rft.issn=15216543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-24 N1 - Date created - 2005-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incidences of selected lesions in control female Harlan Sprague-Dawley rats from two-year studies performed by the National Toxicology Program. AN - 68062938; 16036865 AB - The NTP has a long history of using Fischer rats and has compiled a large database of incidences of lesions seen in control animals. Such a database is lacking for Harlan Sprague-Dawley (SD) rats. The intention of this paper is to report spontaneous lesions observed in female vehicle control Harlan SD rats, and to compare the incidence in 2 strains of rats (Fischer and Harlan SD) used in NTP studies. Female Harlan SD rats served as the test animals for a special series of 2-year studies. Male rats were not used in these studies. Complete histopathology was performed on all animals, and the pathology results underwent comprehensive NTP pathology peer review. The most commonly observed neoplasms in these female control Harlan SD rats were mammary gland fibroadenoma (71%), tumors of the pars distalis of the pituitary (41%) and thyroid gland C-cell tumors (30%). Female Fischer rats had incidences of 44% for mammary gland fibroadenomas, 34% for tumors of the pars distalis, and 16% for thyroid gland C-cell tumors. Fischer rats had a 15% incidence of clitoral gland tumors, while the Harlan SD rats had an incidence of < 1%. In contrast to Fischer F344 rats, the Harlan SD rats had a high incidence of squamous metaplasia of the uterus (44.2%). Squamous metaplasia is not a lesion commonly observed in NTP control Fischer rats. The Harlan SD rats had a very low incidence of mononuclear cell leukemia (0.5%), compared with an incidence of 24% in female Fischer rats. JF - Toxicologic pathology AU - Brix, Amy E AU - Nyska, Abraham AU - Haseman, Joseph K AU - Sells, Donald M AU - Jokinen, Micheal P AU - Walker, Nigel J AD - Experimental Pathology Laboratories, PO Box 12766, Research Triangle Park, NC 27709, USA. brix@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 477 EP - 483 VL - 33 IS - 4 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Rats KW - Animals KW - United States Dept. of Health and Human Services -- organization & administration KW - Toxicity Tests, Chronic KW - Carcinogenicity Tests KW - United States -- epidemiology KW - Female KW - Neoplasms -- veterinary KW - Rats, Sprague-Dawley KW - Neoplasms -- pathology KW - Rodent Diseases -- epidemiology KW - Neoplasms -- epidemiology KW - Rodent Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68062938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Incidences+of+selected+lesions+in+control+female+Harlan+Sprague-Dawley+rats+from+two-year+studies+performed+by+the+National+Toxicology+Program.&rft.au=Brix%2C+Amy+E%3BNyska%2C+Abraham%3BHaseman%2C+Joseph+K%3BSells%2C+Donald+M%3BJokinen%2C+Micheal+P%3BWalker%2C+Nigel+J&rft.aulast=Brix&rft.aufirst=Amy&rft.date=2005-01-01&rft.volume=33&rft.issue=4&rft.spage=477&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 - 2005-09-19 N1 - Date created - 2005-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of azoxymethane-induced aberrant crypt foci in rat by diphenylmethyl selenocyanate through downregulation of COX-2 and modulation of glutathione-S-transferase and lipid peroxidation. AN - 68058852; 16034162 AB - Preventive intervention of colorectal cancer has become essential, as a major portion of the population could develop the disease at some point during their lives. An inverse association between dietary intake of selenium, an important biological trace element, and colorectal cancer risk has been observed through epidemiological and experimental studies. Inhibitory activity of an organoselenocyanate, diphenylmethylselenocyanate, was tested on azoxymethane (15 mg/kg body wt) induced colon carcinogenesis in Sprague-Dawley rats. Pretreatment and concomitant treatment, at a dose of 2 mg/kg body wt, was carried out and the effect was observed on aberrant crypt foci, the preneoplastic lesion. To investigate the mechanism of action of the compound, lipid peroxidation level and glutathione-S-transferase (GST) activities were assessed in the liver as well as in the colon. Expression of cyclooxygenase-2 protein, inducible during colon carcinogenesis, was also analyzed in the colon. Inhibitory activity of the compound was shown by the reduced incidences of aberrant crypt foci in the treated groups (by 63.3%, p=0.00044 in the pretreated group, and by 44%, p=0.0067 in the concomitant treatment group). Significant induction of GST activities and significant reduction in lipid peroxidation level both in the liver as well as in the colon and suppression of cyclooxygenase-2 expression in the colon of the treated groups suggest that the compound could exert its preventive effect at different levels of the carcinogenic process. The preventive effect was better in the pretreatment group than in the concomitant treatment group, suggesting some added protection to the target tissue resulting from preadministration of the compound. JF - Biological trace element research AU - Ghosh, Samit AU - Das, Rajat Kumar AU - Sengupta, Archana AU - Bhattacharya, Sudin AD - Department of Cancer Chemoprevention, Chittaranajan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata-700026, India. Y1 - 2005 PY - 2005 DA - 2005 SP - 171 EP - 185 VL - 105 IS - 1-3 SN - 0163-4984, 0163-4984 KW - Organoselenium Compounds KW - 0 KW - diphenylmethyl selenocyanate KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Selenium KW - H6241UJ22B KW - Azoxymethane KW - MO0N1J0SEN KW - Index Medicus KW - Animals KW - Liver -- enzymology KW - Electrophoresis, Polyacrylamide Gel KW - Lipid Peroxidation KW - Rats KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Colon -- enzymology KW - Neoplasms, Experimental -- chemically induced KW - Colon -- metabolism KW - Models, Chemical KW - Neoplasms, Experimental -- drug therapy KW - Time Factors KW - Colorectal Neoplasms -- prevention & control KW - Male KW - Organoselenium Compounds -- pharmacology KW - Down-Regulation KW - Azoxymethane -- toxicity KW - Glutathione Transferase -- metabolism KW - Glutathione Transferase -- biosynthesis KW - Selenium -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68058852?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+trace+element+research&rft.atitle=Inhibition+of+azoxymethane-induced+aberrant+crypt+foci+in+rat+by+diphenylmethyl+selenocyanate+through+downregulation+of+COX-2+and+modulation+of+glutathione-S-transferase+and+lipid+peroxidation.&rft.au=Ghosh%2C+Samit%3BDas%2C+Rajat+Kumar%3BSengupta%2C+Archana%3BBhattacharya%2C+Sudin&rft.aulast=Ghosh&rft.aufirst=Samit&rft.date=2005-01-01&rft.volume=105&rft.issue=1-3&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Biological+trace+element+research&rft.issn=01634984&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-11-03 N1 - Date created - 2005-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Daubert motion: a legal strategy to exclude essential scientific evidence in toxic tort litigation. AN - 68056797; 16030335 AB - In the US Supreme Court's Daubert v Merrell Dow Pharmaceuticals, Inc decision, federal judges were directed to examine the scientific method underlying expert evidence and admit that which is scientifically reliable and relevant. However, if a judge does not have adequate training or experience in dealing with scientific uncertainty, understand the full value or limit of currently used methodologies, or recognize hidden assumptions, misrepresentations of scientific data, or the strengths of scientific inferences, he or she may reach an incorrect decision on the reliability and relevance of evidence linking environmental factors to human disease. This could lead to the unfair exclusion of valid scientific evidence, particularly that which is essential to a plaintiff's case in toxic tort litigation. JF - American journal of public health AU - Melnick, Ronald L AD - Environmental Toxicology Program, National Institute for Environmental Health Sciences, National Institutes of Health, Bethesda, MD, USA. melnickr@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - S30 EP - S34 VL - 95 Suppl 1 SN - 0090-0036, 0090-0036 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Causality KW - Uncertainty KW - Humans KW - Supreme Court Decisions KW - Government Regulation KW - Judicial Role KW - Environmental Exposure -- legislation & jurisprudence KW - Science -- legislation & jurisprudence KW - Public Policy KW - Liability, Legal KW - Science -- methods KW - Expert Testimony -- legislation & jurisprudence KW - Drug Industry -- legislation & jurisprudence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68056797?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+public+health&rft.atitle=A+Daubert+motion%3A+a+legal+strategy+to+exclude+essential+scientific+evidence+in+toxic+tort+litigation.&rft.au=Melnick%2C+Ronald+L&rft.aulast=Melnick&rft.aufirst=Ronald&rft.date=2005-01-01&rft.volume=95+Suppl+1&rft.issue=&rft.spage=S30&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-22 N1 - Date created - 2005-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - "A doctors' war": expert witnesses in late 19th-century America. AN - 68055930; 16030334 JF - American journal of public health AU - Fee, Elizabeth AU - Brown, Theodore M AD - History of Medicine Division, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. elizabeth_fee@nlm.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - S28 EP - S29 VL - 95 Suppl 1 SN - 0090-0036, 0090-0036 KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Baltimore KW - Lawyers KW - Humans KW - History, 19th Century KW - Female KW - Forensic Medicine -- history KW - Forensic Medicine -- legislation & jurisprudence KW - Homicide -- legislation & jurisprudence KW - Poisoning -- history KW - Homicide -- history KW - Expert Testimony -- legislation & jurisprudence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68055930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+public+health&rft.atitle=%22A+doctors%27+war%22%3A+expert+witnesses+in+late+19th-century+America.&rft.au=Fee%2C+Elizabeth%3BBrown%2C+Theodore+M&rft.aulast=Fee&rft.aufirst=Elizabeth&rft.date=2005-01-01&rft.volume=95+Suppl+1&rft.issue=&rft.spage=S28&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-22 N1 - Date created - 2005-07-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein engineering of interferon alphas. AN - 68010361; 16000855 AB - Interferon (IFN)-alphas constitute a family of proteins exhibiting high degree of homology in primary, secondary, and tertiary structure and display a high level of species specificity in their biological properties. However, small structural differences in these proteins may be responsible for a significant variety of biological actions. Understanding the structure and function of human IFN-alpha is very important. Recombinant techniques are important tools for the production and modification of IFN proteins. The first IFN hybrid, IFN-alpha1/alpha2 was constructed using recombinant technology in 1981. Subsequently, a number of IFN hybrids and mutants have been constructed, expressed and characterized. These hybrids and mutants have resulted in novel IFNs that either combine different biological properties from the parental proteins or have significantly different biological activity. Therefore, IFN hybrids and mutants have provided a powerful tool for studying the structure and function of these molecules. Also, these engineered IFNs may have important new therapeutic applications and may provide greater sights into understanding of the clinical activities of these molecules. JF - Methods in molecular medicine AU - Hu, Renqiu AU - Lei, Ke-Jian AU - Bekisz, Joseph AU - Zoon, Kathryn C AD - Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 69 EP - 80 VL - 116 SN - 1543-1894, 1543-1894 KW - Interferon-alpha KW - 0 KW - Protein Isoforms KW - Recombinant Fusion Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Humans KW - Polymerase Chain Reaction -- methods KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Conformation KW - Recombinant Fusion Proteins -- metabolism KW - Interferon-alpha -- metabolism KW - Protein Isoforms -- chemistry KW - Interferon-alpha -- chemistry KW - Protein Isoforms -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Protein Engineering -- methods KW - Interferon-alpha -- genetics KW - Protein Isoforms -- genetics KW - Protein Engineering -- instrumentation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/68010361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Methods+in+molecular+medicine&rft.atitle=Protein+engineering+of+interferon+alphas.&rft.au=Hu%2C+Renqiu%3BLei%2C+Ke-Jian%3BBekisz%2C+Joseph%3BZoon%2C+Kathryn+C&rft.aulast=Hu&rft.aufirst=Renqiu&rft.date=2005-01-01&rft.volume=116&rft.issue=&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Methods+in+molecular+medicine&rft.issn=15431894&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-27 N1 - Date created - 2005-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A study on immunological responses to exposures encountered in corn farming. AN - 67993278; 15977189 JF - Journal of biochemical and molecular toxicology AU - Vermeulen, R AU - De Roos, A J AU - Bakke, B AU - Blair, A AU - Hildesheim, A AU - Pinto, L AU - Gillette, P P AU - Lynch, C F AU - Allen, R H AU - Alavanja, M C AD - Division of Cancer Epidemiology and Genetics, NCI, Rockville, MD-20892, USA. vermeulr@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 172 VL - 19 IS - 3 SN - 1095-6670, 1095-6670 KW - Biomarkers KW - 0 KW - Pesticides KW - Index Medicus KW - T-Lymphocytes -- metabolism KW - Humans KW - Biomarkers -- analysis KW - Adult KW - Surveys and Questionnaires KW - Middle Aged KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- immunology KW - Male KW - Agriculture KW - Immunity -- immunology KW - Zea mays KW - Pesticides -- pharmacology KW - Immunity -- drug effects KW - Pesticides -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67993278?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biochemical+and+molecular+toxicology&rft.atitle=A+study+on+immunological+responses+to+exposures+encountered+in+corn+farming.&rft.au=Vermeulen%2C+R%3BDe+Roos%2C+A+J%3BBakke%2C+B%3BBlair%2C+A%3BHildesheim%2C+A%3BPinto%2C+L%3BGillette%2C+P+P%3BLynch%2C+C+F%3BAllen%2C+R+H%3BAlavanja%2C+M+C&rft.aulast=Vermeulen&rft.aufirst=R&rft.date=2005-01-01&rft.volume=19&rft.issue=3&rft.spage=172&rft.isbn=&rft.btitle=&rft.title=Journal+of+biochemical+and+molecular+toxicology&rft.issn=10956670&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-20 N1 - Date created - 2005-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Agricultural Health Study biomarker workshop on cancer etiology. Introduction: overview of study design, results, and goals of workshop. AN - 67992365; 15977198 JF - Journal of biochemical and molecular toxicology AU - Bonner, Matthew R AU - Alavanja, Michael C R AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892-7240, USA. bonnerm@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 169 EP - 171 VL - 19 IS - 3 SN - 1095-6670, 1095-6670 KW - Biomarkers, Tumor KW - 0 KW - Pesticides KW - Index Medicus KW - Risk Factors KW - Humans KW - Cohort Studies KW - North Carolina -- epidemiology KW - Iowa -- epidemiology KW - Pesticides -- toxicity KW - Goals KW - Agriculture KW - Health Surveys KW - Neoplasms -- epidemiology KW - Research Design KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67992365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biochemical+and+molecular+toxicology&rft.atitle=The+Agricultural+Health+Study+biomarker+workshop+on+cancer+etiology.+Introduction%3A+overview+of+study+design%2C+results%2C+and+goals+of+workshop.&rft.au=Bonner%2C+Matthew+R%3BAlavanja%2C+Michael+C+R&rft.aulast=Bonner&rft.aufirst=Matthew&rft.date=2005-01-01&rft.volume=19&rft.issue=3&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Journal+of+biochemical+and+molecular+toxicology&rft.issn=10956670&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-20 N1 - Date created - 2005-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA replication and repair reactions relevant to the AHS. AN - 67992136; 15977194 JF - Journal of biochemical and molecular toxicology AU - Kunkel, Thomas A AD - Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS Research Triangle Park, NC 27709, USA. kunkel@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 190 EP - 191 VL - 19 IS - 3 SN - 1095-6670, 1095-6670 KW - DNA KW - 9007-49-2 KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Animals KW - Humans KW - Mutagenesis -- genetics KW - DNA-Directed DNA Polymerase -- metabolism KW - Agriculture KW - DNA Repair KW - DNA -- metabolism KW - Health Surveys KW - DNA -- genetics KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67992136?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biochemical+and+molecular+toxicology&rft.atitle=DNA+replication+and+repair+reactions+relevant+to+the+AHS.&rft.au=Kunkel%2C+Thomas+A&rft.aulast=Kunkel&rft.aufirst=Thomas&rft.date=2005-01-01&rft.volume=19&rft.issue=3&rft.spage=190&rft.isbn=&rft.btitle=&rft.title=Journal+of+biochemical+and+molecular+toxicology&rft.issn=10956670&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-20 N1 - Date created - 2005-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polyamines stimulate the formation of mutagenic 1,N2-propanodeoxyguanosine adducts from acetaldehyde. AN - 67967507; 15972793 AB - Alcoholic beverage consumption is associated with an increased risk of upper gastrointestinal cancer. Acetaldehyde (AA), the first metabolite of ethanol, is a suspected human carcinogen, but the molecular mechanisms underlying AA carcinogenicity are unclear. In this work, we tested the hypothesis that polyamines could facilitate the formation of mutagenic alpha-methyl-gamma-hydroxy-1,N2-propano-2'-deoxyguanosine (Cr-PdG) adducts from biologically relevant AA concentrations. We found that Cr-PdG adducts could be formed by reacting deoxyguanosine with muM concentrations of AA in the presence of spermidine, but not with either AA or spermidine alone. The identities of the Cr-PdG adducts were confirmed by both liquid and gas chromatography-mass spectrometry. Using a novel isotope-dilution liquid chromatography-mass spectrometry assay, we found that in the presence of 5 mM spermidine, AA concentrations of 100 microM and above resulted in the formation of Cr-PdG in genomic DNA. These AA levels are within the range that occurs in human saliva after alcoholic beverage consumption. We also showed that spermidine directly reacts with AA to generate crotonaldehyde (CrA), most likely via an enamine aldol condensation mechanism. We propose that AA derived from ethanol metabolism is converted to CrA by polyamines in dividing cells, forming Cr-PdG adducts, which may be responsible for the carcinogenicity of alcoholic beverage consumption. JF - Nucleic acids research AU - Theruvathu, Jacob A AU - Jaruga, Pawel AU - Nath, Raghu G AU - Dizdaroglu, Miral AU - Brooks, P J AD - Section on Molecular Neurobiology, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH 5625 Fishers Lane, Room 3S32, MSC 9412, Bethesda, MD 20952-9412, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 3513 EP - 3520 VL - 33 IS - 11 KW - Aldehydes KW - 0 KW - DNA Adducts KW - alpha-methyl-gamma-hydroxy-1,N2-propano-2'-deoxyguanosine KW - 1,N(2)-propanodeoxyguanosine KW - 120667-07-4 KW - 2-butenal KW - 9G72074TUW KW - Deoxyguanosine KW - G9481N71RO KW - Acetaldehyde KW - GO1N1ZPR3B KW - Spermidine KW - U87FK77H25 KW - Index Medicus KW - Aldehydes -- chemistry KW - Humans KW - Gas Chromatography-Mass Spectrometry KW - Deoxyguanosine -- metabolism KW - Spermidine -- chemistry KW - DNA Adducts -- chemistry KW - Spermidine -- pharmacology KW - Acetaldehyde -- chemistry KW - Acetaldehyde -- metabolism KW - Deoxyguanosine -- chemistry KW - DNA Adducts -- metabolism KW - Mutagenesis KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67967507?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Polyamines+stimulate+the+formation+of+mutagenic+1%2CN2-propanodeoxyguanosine+adducts+from+acetaldehyde.&rft.au=Theruvathu%2C+Jacob+A%3BJaruga%2C+Pawel%3BNath%2C+Raghu+G%3BDizdaroglu%2C+Miral%3BBrooks%2C+P+J&rft.aulast=Theruvathu&rft.aufirst=Jacob&rft.date=2005-01-01&rft.volume=33&rft.issue=11&rft.spage=3513&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 - 2005-07-11 N1 - Date created - 2005-06-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: IARC Sci Publ. 1999;(150):219-32 [10626223] Carcinogenesis. 1998 Aug;19(8):1383-7 [9744533] Alcohol Clin Exp Res. 2000 Jun;24(6):873-7 [10888077] Chem Res Toxicol. 2000 Nov;13(11):1149-57 [11087437] J Biol Chem. 2001 Mar 23;276(12):9077-82 [11054428] Biochemistry. 2001 Apr 3;40(13):4106-14 [11300791] Chem Res Toxicol. 2001 Nov;14(11):1506-12 [11712908] Pathol Biol (Paris). 2001 Nov;49(9):676-82 [11762128] Biochemistry. 2002 Mar 19;41(11):3703-11 [11888287] Chem Res Toxicol. 2002 Mar;15(3):367-72 [11896684] Methods Enzymol. 2002;353:523-36 [12078524] Science. 2002 Jul 26;297(5581):606-9 [12065746] Carcinogenesis. 2002 Nov;23(11):1781-9 [12419825] Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16660-5 [12486230] J Am Chem Soc. 2003 Jan 8;125(1):50-61 [12515506] Annu Rev Pharmacol Toxicol. 2003;43:485-520 [12415124] J Biol Chem. 2003 Feb 21;278(8):5970-6 [12502710] Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2261-5 [12591940] Jpn J Clin Oncol. 2003 Mar;33(3):111-21 [12672787] Crit Rev Clin Lab Sci. 2003 Apr;40(2):183-208 [12755455] Bioorg Med Chem Lett. 2003 Oct 20;13(20):3497-8 [14505656] Chem Res Toxicol. 2003 Dec;16(12):1616-23 [14680376] Biol Pharm Bull. 2004 Mar;27(3):273-6 [14993787] Environ Mol Mutagen. 2005 Jun;45(5):455-9 [15690339] Alcohol Alcohol. 2004 May-Jun;39(3):155-65 [15082451] Gut. 2004 Jun;53(6):871-6 [15138216] Nucleic Acids Res. 2004;32(11):e87 [15215337] DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1063-9 [15279794] Nucleic Acids Res. 2004;32(18):5685-92 [15498925] Nat Rev Cancer. 2004 Oct;4(10):781-92 [15510159] Mutat Res. 1979 Nov;68(3):291-4 [514307] Mutat Res. 1980 Dec;73(2):377-86 [7464846] Annu Rev Biochem. 1984;53:749-90 [6206782] Toxicology. 1986 Oct;41(2):213-31 [3764943] Mutat Res. 1987 Nov;186(3):177-200 [3313027] Mutat Res. 1988 Jan;195(1):1-20 [3122032] Biochemistry. 1999 Jan 19;38(3):929-35 [9893988] Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6615-20 [10359760] Am J Hum Genet. 1999 Sep;65(3):795-807 [10441588] Environ Mol Mutagen. 2005;45(1):62-9 [15611981] Chem Res Toxicol. 2005 Apr;18(4):711-21 [15833031] Gastroenterology. 1990 Feb;98(2):406-13 [2295396] Biol Chem Hoppe Seyler. 1989 Dec;370(12):1279-84 [2482746] Carcinogenesis. 1992 Nov;13(11):2095-100 [1423881] Alcohol Alcohol Suppl. 1991;1:271-6 [1845549] Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7491-5 [8052609] Alcohol. 1995 Mar-Apr;12(2):111-5 [7772260] Carcinogenesis. 1995 Sep;16(9):2177-85 [7554072] Chem Biol Interact. 1995 Oct 20;98(1):51-67 [7586051] Radiat Res. 1996 Jun;145(6):776-80 [8643839] Carcinogenesis. 1997 Apr;18(4):627-32 [9111191] Carcinogenesis. 1997 Sep;18(9):1739-43 [9328169] Radiat Res. 1998 Jun;149(6):543-9 [9611092] Alcohol Clin Exp Res. 1998 Aug;22(5):1161-4 [9726290] Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11140-5 [9736703] Int J Biochem Cell Biol. 2000 Mar;32(3):289-301 [10716626] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of a complex 125I-induced DNA double-strand break: implications for repair. AN - 67944445; 15962759 AB - To examine the role of radiation-induced DNA double-strand break (DSB) structural organization in DSB repair, and characterize the structural features of 125I-induced DSBs that may impact the repair process. Plasmid DNA was linearized by sequence-specific targeting using an 125I-labeled triplex-forming oligonucleotide (TFO). Following isolation from agarose gels, base damage structures associated with the DSB ends in plasmids linearized by the 125I-TFO were characterized by probing with the E. coli DNA damage-specific endonuclease and DNA-glycosylases, endonuclease IV (endo IV), endonuclease III (endo III), and formamidopyrimidine-glycosylase (Fpg). Plasmid DNA containing DSBs produced by the high-LET-like effects of 125I-TFO has been shown to support at least 2-fold lower end joining than gamma-ray linearized plasmid, and this may be a consequence of the highly complex structure expected near an 125I-induced DSB end. Therefore, to determine if a high density of base damage exists proximal to the DSBs produced by 125I-TFOs, short fragments of DNA recovered from the DSB end of 125I-TFO-linearized plasmid were enzymatically probed. Base damage and AP site clustering was demonstrated within 3 bases downstream and 7 bases upstream of the targeted base. Furthermore, the pattern and extent of base damage varied depending upon the presence or absence of 2 M DMSO during irradiation. 125I-TFO-induced DSBs exhibit a high degree of base damage clustering proximal to the DSB end. At least 60% of the nucleotides within 10 bp of the 125I decay site are sensitive to cleavage by endo IV, endo III, or Fpg following damage accumulation in the presence of DMSO, whereas > or = 80% are sensitive in the absence of DMSO. The high degree of base damage clustering associated with the 125I-TFO-induced DSB end may be a major factor leading to its negligible in vitro repair by the non-homologous end-joining pathway (NHEJ). JF - International journal of radiation biology AU - Datta, Kamal AU - Neumann, Ronald D AU - Winters, Thomas A AD - Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 13 EP - 21 VL - 81 IS - 1 SN - 0955-3002, 0955-3002 KW - DNA, Circular KW - 0 KW - Iodine Radioisotopes KW - Oligonucleotide Probes KW - Oligonucleotides KW - Index Medicus KW - Space life sciences KW - Humans KW - DNA, Circular -- physiology KW - Plasmids -- physiology KW - DNA, Circular -- radiation effects KW - Plasmids -- radiation effects KW - DNA Repair -- radiation effects KW - DNA Repair -- physiology KW - DNA Damage -- physiology KW - Iodine Radioisotopes -- adverse effects KW - DNA Damage -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67944445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Characterization+of+a+complex+125I-induced+DNA+double-strand+break%3A+implications+for+repair.&rft.au=Datta%2C+Kamal%3BNeumann%2C+Ronald+D%3BWinters%2C+Thomas+A&rft.aulast=Datta&rft.aufirst=Kamal&rft.date=2005-01-01&rft.volume=81&rft.issue=1&rft.spage=13&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 - 2005-07-15 N1 - Date created - 2005-06-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Int J Radiat Biol. 2005 Jan;81(1):table of contents N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Chernobyl disaster: cancer following the accident at the Chernobyl nuclear power plant. AN - 67938339; 15958427 JF - Epidemiologic reviews AU - Hatch, M AU - Ron, E AU - Bouville, A AU - Zablotska, L AU - Howe, G AD - National Cancer Institute, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Institutes of Health, Department of Health and Human Services, Rockville, MD 20852, USA. hatchm@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 56 EP - 66 VL - 27 SN - 0193-936X, 0193-936X KW - Index Medicus KW - Ukraine -- epidemiology KW - Chernobyl Nuclear Accident KW - Radiometry KW - Humans KW - Radioactive Hazard Release KW - Neoplasms, Radiation-Induced -- epidemiology KW - Neoplasms, Radiation-Induced -- classification KW - Nuclear Reactors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67938339?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiologic+reviews&rft.atitle=The+Chernobyl+disaster%3A+cancer+following+the+accident+at+the+Chernobyl+nuclear+power+plant.&rft.au=Hatch%2C+M%3BRon%2C+E%3BBouville%2C+A%3BZablotska%2C+L%3BHowe%2C+G&rft.aulast=Hatch&rft.aufirst=M&rft.date=2005-01-01&rft.volume=27&rft.issue=&rft.spage=56&rft.isbn=&rft.btitle=&rft.title=Epidemiologic+reviews&rft.issn=0193936X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-20 N1 - Date created - 2005-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The biochemistry of Parkinson's disease. AN - 67930213; 15952880 AB - Several genes have been identified for monogenic disorders that variably resemble Parkinson's disease. Dominant mutations in the gene encoding alpha-synuclein enhance the propensity of this protein to aggregate. As a consequence, these patients have a widespread disease with protein inclusion bodies in several brain areas. In contrast, mutations in several recessive genes (parkin, DJ-1, and PINK1) produce neuronal cell loss but generally without protein aggregation pathology. Progress has been made in understanding some of the mechanisms of toxicity: Parkin is an E3 ubiquitin ligase and DJ-1 and PINK1 appear to protect against mitochondrial damage. However, we have not yet fully resolved how the recessive genes relate to alpha-synuclein, or whether they represent different ways to induce a similar phenotype. JF - Annual review of biochemistry AU - Cookson, Mark R AD - Cell Biology Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland 20892, USA. cookson@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 29 EP - 52 VL - 74 SN - 0066-4154, 0066-4154 KW - Intracellular Signaling Peptides and Proteins KW - 0 KW - Multiprotein Complexes KW - Nerve Tissue Proteins KW - Oncogene Proteins KW - SNCA protein, human KW - Synucleins KW - alpha-Synuclein KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - parkin protein KW - Protein Kinases KW - EC 2.7.- KW - PTEN-induced putative kinase KW - EC 2.7.11.1 KW - PARK7 protein, human KW - EC 3.1.2.- KW - Protein Deglycase DJ-1 KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Proteasome Endopeptidase Complex -- chemistry KW - Humans KW - Oncogene Proteins -- chemistry KW - Oncogene Proteins -- genetics KW - Nerve Tissue Proteins -- genetics KW - Models, Biological KW - Ubiquitin-Protein Ligases -- chemistry KW - Phenotype KW - Ubiquitin-Protein Ligases -- genetics KW - Protein Kinases -- genetics KW - Proteasome Endopeptidase Complex -- genetics KW - Nerve Tissue Proteins -- chemistry KW - Mutation KW - Genes, Recessive KW - Protein Kinases -- chemistry KW - Parkinson Disease -- metabolism KW - Parkinson Disease -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67930213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+biochemistry&rft.atitle=The+biochemistry+of+Parkinson%27s+disease.&rft.au=Cookson%2C+Mark+R&rft.aulast=Cookson&rft.aufirst=Mark&rft.date=2005-01-01&rft.volume=74&rft.issue=&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+biochemistry&rft.issn=00664154&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-29 N1 - Date created - 2005-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lifestyle factors, exposures, genetic susceptibility, and renal cell cancer risk: a review. AN - 67922531; 15945510 AB - Malignant kidney tumors account for approximately 2% of all new primary cancer cases diagnosed in the United States, with an estimated 30,000 cases occurring annually. Although a variety of agents, chemical and biological, have been implicated as causal agents in the development of renal cell carcinoma (RCC), the etiology remains enigmatic. The strongest association has been developed between cigarette smoking and renal cancer however consistent, positive associations between RCC and obesity, diabetes, and hypertension have also been reported. In addition, more recent investigations of familial kidney cancer syndromes indicate that a strong genetic component contributes to RCC development. Several genes have been identified through investigation of familial kidney cancer syndromes. This review article describes recent trends in RCC incidence and the currently identifiable etiological causes that account for approximately half of the RCC cases diagnoses. The remainder of this review then focuses on additional risk factors that have thus far not been well examined but may be helpful in explaining the increasing incidence trends and the geographic or racial variation observed nationally and worldwide. JF - Cancer investigation AU - Moore, Lee E AU - Wilson, Robin T AU - Campleman, Sharan L AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA. moorele@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 240 EP - 255 VL - 23 IS - 3 SN - 0735-7907, 0735-7907 KW - Index Medicus KW - Risk Factors KW - Humans KW - Life Style KW - Carcinoma, Renal Cell -- etiology KW - Occupational Exposure -- adverse effects KW - Kidney Neoplasms -- etiology KW - Genetic Predisposition to Disease KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67922531?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+investigation&rft.atitle=Lifestyle+factors%2C+exposures%2C+genetic+susceptibility%2C+and+renal+cell+cancer+risk%3A+a+review.&rft.au=Moore%2C+Lee+E%3BWilson%2C+Robin+T%3BCampleman%2C+Sharan+L&rft.aulast=Moore&rft.aufirst=Lee&rft.date=2005-01-01&rft.volume=23&rft.issue=3&rft.spage=240&rft.isbn=&rft.btitle=&rft.title=Cancer+investigation&rft.issn=07357907&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-28 N1 - Date created - 2005-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cripto-1: an oncofetal gene with many faces. AN - 67921275; 15949532 AB - Human Cripto-1 (CR-1), a member of the epidermal growth factor (EGF)-CFC family, has been implicated in embryogenesis and in carcinogenesis. During early vertebrate development, CR-1 functions as a co-receptor for Nodal, a transforming growth factor beta (TGFbeta) family member and is essential for mesoderm and endoderm formation and anterior-posterior and left-right axis establishment. In adult tissues, CR-1 is expressed at a low level in all stages of mammary gland development and expression increases during pregnancy and lactation. Overexpression of CR-1 in mouse mammary epithelial cells leads to their transformation in vitro and, when injected into mammary glands, produces ductal hyperplasias. CR-1 can also enhance migration, invasion, branching morphogenesis and epithelial to mesenchymal transition (EMT) of several mouse mammary epithelial cell lines. Furthermore, transgenic mouse studies have shown that overexpression of a human CR-1 transgene in the mammary gland under the transcriptional control of the mouse mammary tumor virus (MMTV) promoter results in mammary hyperplasias and papillary adenocarcinomas. Finally, CR-1 is expressed at high levels in approximately 50 to 80% of different types of human carcinomas, including breast, cervix, colon, stomach, pancreas, lung, ovary, and testis. In conclusion, EGF-CFC proteins play dual roles as embryonic pattern formation genes and as oncogenes. While during embryogenesis EGF-CFC proteins perform specific and regulatory functions related to cell and tissue patterning, inappropriate expression of these molecules in adult tissues can lead to cellular proliferation and transformation and therefore may be important in the etiology and/or progression of cancer. JF - Current topics in developmental biology AU - Bianco, Caterina AU - Strizzi, Luigi AU - Normanno, Nicola AU - Khan, Nadia AU - Salomon, David S AD - Tumor Growth Factor Section, Mammary Biology & Tumorigenesis Laboratory Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 85 EP - 133 VL - 67 KW - GPI-Linked Proteins KW - 0 KW - Growth Substances KW - Intercellular Signaling Peptides and Proteins KW - Membrane Glycoproteins KW - Neoplasm Proteins KW - TDGF1 protein, human KW - Epidermal Growth Factor KW - 62229-50-9 KW - Index Medicus KW - Humans KW - Growth Substances -- physiology KW - Neoplasm Proteins -- physiology KW - Membrane Glycoproteins -- physiology KW - Neoplasms -- etiology KW - Neoplasms -- metabolism KW - Epidermal Growth Factor -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67921275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+topics+in+developmental+biology&rft.atitle=Cripto-1%3A+an+oncofetal+gene+with+many+faces.&rft.au=Bianco%2C+Caterina%3BStrizzi%2C+Luigi%3BNormanno%2C+Nicola%3BKhan%2C+Nadia%3BSalomon%2C+David+S&rft.aulast=Bianco&rft.aufirst=Caterina&rft.date=2005-01-01&rft.volume=67&rft.issue=&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Current+topics+in+developmental+biology&rft.issn=1557-8933&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2009-09-22 N1 - Date created - 2005-06-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic profiling of human hepatocellular carcinoma. AN - 67871484; 15918141 AB - The underlying molecular basis for the heterogeneity in human liver cancer, hepatocellular carcinoma (HCC), is largely unknown. As with most other human cancers, the heterogeneous nature of HCC has hampered both treatment and prognostic predictions. Global gene expression profiling of human cancers is a promising new technology for refining the diagnosis and prognosis of HCC as well as for identifying potential therapeutic targets. Improved molecular characterization of HCC from gene expression profiling studies will undoubtedly improve the prediction of treatment responses, improve the selection of treatments for specific molecular subtypes of HCC, and ultimately improve the clinical outcome of HCC patients. We review the recent advances in gene expression profiling of HCC and discuss the biological and clinical insights obtained from these studies. JF - Seminars in liver disease AU - Lee, Ju-Seog AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4262, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 125 EP - 132 VL - 25 IS - 2 SN - 0272-8087, 0272-8087 KW - Index Medicus KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Prognosis KW - Disease Models, Animal KW - Mice KW - Gene Expression Profiling KW - Carcinoma, Hepatocellular -- diagnosis KW - Carcinoma, Hepatocellular -- drug therapy KW - Liver Neoplasms -- drug therapy KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- mortality KW - Liver Neoplasms -- diagnosis KW - Carcinoma, Hepatocellular -- mortality KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67871484?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+profiling+of+human+hepatocellular+carcinoma.&rft.au=Lee%2C+Ju-Seog%3BThorgeirsson%2C+Snorri+S&rft.aulast=Lee&rft.aufirst=Ju-Seog&rft.date=2005-01-01&rft.volume=25&rft.issue=2&rft.spage=125&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 - 2005-09-13 N1 - Date created - 2005-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preclinical manufacture of anti-HER2 liposome-inserting, scFv-PEG-lipid conjugate. 2. Conjugate micelle identity, purity, stability, and potency analysis. AN - 67843562; 15903261 AB - Analytical methods optimized for micellar F5cys-MP-PEG(2000)-DPSE protein-lipopolymer conjugate are presented. The apparent micelle molecular weight, determined by size exclusion chromatography, ranged from 330 to 960 kDa. The F5cys antibody and conjugate melting points, determined by differential scanning calorimetry, were near 82 degrees C. Traditional methods for characterizing monodisperse protein species were inapplicable to conjugate analysis. The isoelectric point of F5cys (9.2) and the conjugate (8.9) were determined by capillary isoelectric focusing (cIEF) after addition of the zwitterionic detergent CHAPS to the buffer. Conjugate incubation with phospholipase B selectively removed DSPE lipid groups and dispersed the conjugate prior to separation by chromatographic methods. Alternatively, adding 2-propanol (29.4 vol %) and n-butanol (4.5 vol %) to buffers for salt-gradient cation exchange chromatography provided gentler, nonenzymatic dispersion, resulting in well-resolved peaks. This method was used to assess stability, identify contaminants, establish lot-to-lot comparability, and determine the average chromatographic purity (93%) for conjugate lots, described previously. The F5cys amino acid content was confirmed after conjugation. The expected conjugate avidity for immobilized HER-2/neu was measured by bimolecular interaction analysis (BIAcore). Mock therapeutic assemblies were made by conjugate insertion into preformed doxorubicin-encapsulating liposomes for antibody-directed uptake of doxorubicin by HER2-overexpressing cancer cells in vitro. Together these developed assays established that the manufacturing method as described in the first part of this study consistently produced F5cys-MP-PEG(2000)-DSPE having sufficient purity, stability, and functionality for use in preclinical toxicology investigations. JF - Biotechnology progress AU - Nellis, David F AU - Giardina, Steven L AU - Janini, George M AU - Shenoy, Shilpa R AU - Marks, James D AU - Tsai, Richard AU - Drummond, Daryl C AU - Hong, Keelung AU - Park, John W AU - Ouellette, Thomas F AU - Perkins, Shelley C AU - Kirpotin, Dmitri B AD - SAIC-Frederick, Inc., National Cancer Institute at Frederick, PO Box B, Frederick, Maryland 21702, USA. PY - 2005 SP - 221 EP - 232 VL - 21 IS - 1 SN - 8756-7938, 8756-7938 KW - Immunoglobulin Fragments KW - 0 KW - Liposomes KW - Micelles KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Lysophospholipase KW - EC 3.1.1.5 KW - Index Medicus KW - Chromatography, Ion Exchange -- methods KW - Electrophoresis, Polyacrylamide Gel KW - Receptor, ErbB-2 -- antagonists & inhibitors KW - Particle Size KW - Temperature KW - Models, Biological KW - Chromatography, High Pressure Liquid KW - Molecular Weight KW - Sequence Analysis, Protein KW - Lysophospholipase -- metabolism KW - Receptor, ErbB-2 -- immunology KW - Time Factors KW - Calorimetry, Differential Scanning KW - Liposomes -- chemistry KW - Immunoglobulin Fragments -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67843562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biotechnology+progress&rft.atitle=Preclinical+manufacture+of+anti-HER2+liposome-inserting%2C+scFv-PEG-lipid+conjugate.+2.+Conjugate+micelle+identity%2C+purity%2C+stability%2C+and+potency+analysis.&rft.au=Nellis%2C+David+F%3BGiardina%2C+Steven+L%3BJanini%2C+George+M%3BShenoy%2C+Shilpa+R%3BMarks%2C+James+D%3BTsai%2C+Richard%3BDrummond%2C+Daryl+C%3BHong%2C+Keelung%3BPark%2C+John+W%3BOuellette%2C+Thomas+F%3BPerkins%2C+Shelley+C%3BKirpotin%2C+Dmitri+B&rft.aulast=Nellis&rft.aufirst=David&rft.date=2005-01-01&rft.volume=21&rft.issue=1&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Biotechnology+progress&rft.issn=87567938&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-07 N1 - Date created - 2005-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of p53 tumor suppressor gene, H-ras protooncogene and proliferating cell nuclear antigen (PCNA) in squamous cell carcinomas of HRA/Skh mice following exposure to 8-methoxypsoralen (8-MOP) and UVA radiation (PUVA therapy). AN - 67841578; 15902973 AB - Treatment with 8-methoxypsoralen (8-MOP) and ultraviolet radiation (primarily UVA), called PUVA therapy, has been used to treat different chronic skin diseases but led to a significant increased risk for skin cancer. The National Toxicology Program (NTP) performed a study in mice treated with PUVA that showed a significant increase in squamous cell carcinomas of the skin. In the present study, we evaluated the protein expression of p53 and PCNA and DNA mutations of p53 and H-ras genes in both hyperplastic and neoplastic squamous cell lesions from the NTP study. By immunohistochemical staining, protein expression of both p53 and PCNA was detected in 3/16 (19%) of hyperplastic lesions and 14/17 (82%) of SCCs in groups treated with both 8-MOP and UVA. The mutation frequency of p53 in SCCs from mice administered 8-MOP plus UVA was 15/17 (88%) with a predominant distribution of mutations in exon 6 (14/15 - 93%). No H-ras mutations were detected in the hyperplastic lesions/tumors. The mutagenic effect of PUVA on the p53 tumor suppressor gene may lead to a conformational modification and inactivation of the p53 protein, which are considered critical steps in PUVA-induced skin carcinogenesis. The p53 mutational frequency and patterns from our study were different from those reported in human PUVA-type tumors. JF - Toxicologic pathology AU - Lambertini, Luca AU - Surin, Kezia AU - Ton, Thai-Vu T AU - Clayton, Natasha AU - Dunnick, June K AU - Kim, Yongbaek AU - Hong, Hue-Hua L AU - Devereux, Theodora R AU - Sills, Robert C AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 292 EP - 299 VL - 33 IS - 2 SN - 0192-6233, 0192-6233 KW - DNA, Neoplasm KW - 0 KW - Proliferating Cell Nuclear Antigen KW - Tumor Suppressor Protein p53 KW - Proto-Oncogene Proteins p21(ras) KW - EC 3.6.5.2 KW - Methoxsalen KW - U4VJ29L7BQ KW - Index Medicus KW - Animals KW - Hyperplasia -- pathology KW - Proto-Oncogene Proteins p21(ras) -- metabolism KW - Skin -- metabolism KW - DNA Mutational Analysis KW - Skin -- pathology KW - Hyperplasia -- metabolism KW - DNA, Neoplasm -- analysis KW - Mice KW - Mice, Nude KW - Tumor Suppressor Protein p53 -- metabolism KW - Methoxsalen -- toxicity KW - Hyperplasia -- genetics KW - Ultraviolet Rays -- adverse effects KW - Tumor Suppressor Protein p53 -- genetics KW - Immunoenzyme Techniques KW - Proto-Oncogene Proteins p21(ras) -- genetics KW - Skin Neoplasms -- genetics KW - Genes, ras KW - PUVA Therapy -- adverse effects KW - Carcinoma, Squamous Cell -- etiology KW - Genes, p53 KW - Carcinoma, Squamous Cell -- pathology KW - Skin Neoplasms -- etiology KW - Carcinoma, Squamous Cell -- genetics KW - Skin Neoplasms -- pathology KW - Mutation KW - Proliferating Cell Nuclear Antigen -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67841578?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+p53+tumor+suppressor+gene%2C+H-ras+protooncogene+and+proliferating+cell+nuclear+antigen+%28PCNA%29+in+squamous+cell+carcinomas+of+HRA%2FSkh+mice+following+exposure+to+8-methoxypsoralen+%288-MOP%29+and+UVA+radiation+%28PUVA+therapy%29.&rft.au=Lambertini%2C+Luca%3BSurin%2C+Kezia%3BTon%2C+Thai-Vu+T%3BClayton%2C+Natasha%3BDunnick%2C+June+K%3BKim%2C+Yongbaek%3BHong%2C+Hue-Hua+L%3BDevereux%2C+Theodora+R%3BSills%2C+Robert+C&rft.aulast=Lambertini&rft.aufirst=Luca&rft.date=2005-01-01&rft.volume=33&rft.issue=2&rft.spage=292&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 - 2005-06-02 N1 - Date created - 2005-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2-Butoxyethanol female-rat model of hemolysis and disseminated thrombosis: X-ray characterization of osteonecrosis and growth-plate suppression. AN - 67839414; 15902971 AB - We recently proposed a chemically induced rat model for human hemolytic disorders associated with thrombosis. The objective of the present investigation was to apply a noninvasive, high-magnification X-ray analysis, the Faxitron radiography system, to characterize the protracted bone damage associated with this 2-butoxyethanol model and to validate it by histopathology. Groups of female Fischer 344 rats were given 0, 250, or 300 mg of 2-butoxyethanol/kg body weight daily for 4 consecutive days. Groups were then sacrificed 2 hours or 26 days after the final treatment. The treated animals displayed a darkened purple-red discoloration on the distal tail. Histopathological evaluation, including phosphotungstic acid-hematoxylin staining of animals sacrificed 2 hours after the final treatment, revealed disseminated thrombosis and infarction in multiple organs, including bones. The Faxitron MX-20 specimen radiography system was used to image selected bones of rats sacrificed 26 days posttreatment. Premature thinning of the growth plate occurred in the calcaneus, lumbar and coccygeal vertebrae, femur, and ilium of the treated animals. Areas of decreased radiographic densities were seen in the diaphysis of the femur of all treated animals. The bones were then examined histologically and showed a range of changes, including loss or damage to growth plates and necrosis of cortical bone. No thrombi were seen in the animals sacrificed at 30 days, but bone and growth plate changes consistent with prior ischemia were noted. The Faxitron proved to be an excellent noninvasive tool that can be used in future studies with this animal model to examine treatment modalities for the chronic effects of human thrombotic disorders. JF - Toxicologic pathology AU - Lewis, Danielle N AU - Nyska, Abraham AU - Johnson, Kennita AU - Malarkey, David E AU - Ward, Sandy AU - Streicker, Michael AU - Shabat, Shay AU - Peddada, Shyamal AU - Nyska, Meir AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-9998, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 272 EP - 282 VL - 33 IS - 2 SN - 0192-6233, 0192-6233 KW - Ethylene Glycols KW - 0 KW - Solvents KW - n-butoxyethanol KW - I0P9XEZ9WV KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Reproducibility of Results KW - Dose-Response Relationship, Drug KW - Radiography -- instrumentation KW - Body Weight -- drug effects KW - Bone and Bones -- diagnostic imaging KW - Female KW - Solvents -- toxicity KW - Osteonecrosis -- chemically induced KW - Ethylene Glycols -- toxicity KW - Growth Plate -- pathology KW - Growth Plate -- diagnostic imaging KW - Disseminated Intravascular Coagulation -- pathology KW - Disease Models, Animal KW - Osteonecrosis -- etiology KW - Disseminated Intravascular Coagulation -- complications KW - Disseminated Intravascular Coagulation -- chemically induced KW - Osteonecrosis -- pathology KW - Growth Plate -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67839414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=2-Butoxyethanol+female-rat+model+of+hemolysis+and+disseminated+thrombosis%3A+X-ray+characterization+of+osteonecrosis+and+growth-plate+suppression.&rft.au=Lewis%2C+Danielle+N%3BNyska%2C+Abraham%3BJohnson%2C+Kennita%3BMalarkey%2C+David+E%3BWard%2C+Sandy%3BStreicker%2C+Michael%3BShabat%2C+Shay%3BPeddada%2C+Shyamal%3BNyska%2C+Meir&rft.aulast=Lewis&rft.aufirst=Danielle&rft.date=2005-01-01&rft.volume=33&rft.issue=2&rft.spage=272&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 - 2005-06-02 N1 - Date created - 2005-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of COX-2 in acute pain and the use of selective COX-2 inhibitors for acute pain relief. AN - 67826789; 15892672 AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain. Cyclooxygenase (COX) enzyme is of particular interest because it is the major target of NSAIDs. Although NSAIDs are remarkably effective in the management of pain and inflammation, their use is limited by several adverse effects including gastrointestinal bleeding and ulceration, impaired renal function, and inhibition of platelet aggregation. Discovery of a second cyclooxygenase, COX-2, led to the hypothesis that NSAID side effects could be decreased, as the inhibition of COX-2 is more directly implicated in ameliorating inflammation while the inhibition of COX-1 is related to adverse effects in the GI tract. This stimulated the development of selective COX-2 inhibitors (coxibs) that are better tolerated than nonselective NSAIDs but comparable in analgesic efficacy. This article provides an overview on the therapeutic use of selective COX-2 inhibitors for relief of acute pain, largely based on clinical trials in patients undergoing the surgical removal of impacted third molars, with focus on analgesic efficacy and the potential safety associated with their use compared to dual COX-1/COX-2 inhibitors. JF - Current pharmaceutical design AU - Lee, Y AU - Rodriguez, C AU - Dionne, R A AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, National Institute of Health, Building 10 Rm 1N103, 10 Center Drive, Bethesda, MD 20892, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 1737 EP - 1755 VL - 11 IS - 14 SN - 1381-6128, 1381-6128 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Membrane Proteins KW - Arachidonic Acid KW - 27YG812J1I KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - PTGS1 protein, human KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Acute Disease KW - Animals KW - Oral Surgical Procedures KW - Humans KW - Arachidonic Acid -- metabolism KW - Cyclooxygenase Inhibitors -- therapeutic use KW - Cyclooxygenase Inhibitors -- adverse effects KW - Pain -- etiology KW - Prostaglandin-Endoperoxide Synthases -- physiology KW - Pain -- drug therapy KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67826789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+pharmaceutical+design&rft.atitle=The+role+of+COX-2+in+acute+pain+and+the+use+of+selective+COX-2+inhibitors+for+acute+pain+relief.&rft.au=Lee%2C+Y%3BRodriguez%2C+C%3BDionne%2C+R+A&rft.aulast=Lee&rft.aufirst=Y&rft.date=2005-01-01&rft.volume=11&rft.issue=14&rft.spage=1737&rft.isbn=&rft.btitle=&rft.title=Current+pharmaceutical+design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-02 N1 - Date created - 2005-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of formyl peptide receptor-like 1 (FPRL1/FPR2) in mononuclear phagocyte responses in Alzheimer disease. AN - 67822532; 15888909 AB - Alzheimer disease (AD) is the most common neurodegenerative disease, affecting approx 4 million people in the United States in the year 2000 alone. Amyloid beta (Abeta) deposition, activated glial cells, and neuritic degeneration are the characteristic features of AD. Although the precise cause of AD has yet to be determined, a bulk of evidence suggests that inflammatory responses elicited by elevated Abeta peptides play an important role in the pathogenic process of the disease. In AD brain, mononuclear phagocytes (microglia) accumulate at the sites of Abeta peptide deposition. In vitro, Abeta peptides activate mononuclear phagocytes to release neurotoxic mediators. A number of cell-surface molecules have been reported to act as putative receptors for Abeta peptides, among which the G protein-coupled formyl peptide receptor-like 1 (FPRL1) and its mouse homolog FPR2 have been shown to be expressed by activated microglial cells and mediate the chemotactic activity of the 42 amino acid form of Abeta (Abeta42). FPRL1 also participates in Abeta42 internalization in macrophages and its cytotoxicity for neuronal cells. Therefore, FPRL1 may be involved in the inflammatory aspects of AD. This review discusses recent findings relevant to the function and regulation of FPRL1/FPR2 in mononuclear phagocytes by pro- and antiinflammatory signals and its potential as a therapeutic target in AD. JF - Immunologic research AU - Iribarren, Pablo AU - Zhou, Ye AU - Hu, Jinyue AU - Le, Yingying AU - Wang, Ji Ming AD - Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, Bldg. 560, Frederick, MD 21702, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 165 EP - 176 VL - 31 IS - 3 SN - 0257-277X, 0257-277X KW - Cytokines KW - 0 KW - FPR2 protein, human KW - FPR3 protein, human KW - Receptors, Formyl Peptide KW - Receptors, Lipoxin KW - formyl peptide receptor 2, mouse KW - Index Medicus KW - Animals KW - Humans KW - Cytokines -- metabolism KW - Signal Transduction KW - Receptors, Formyl Peptide -- metabolism KW - Phagocytes -- pathology KW - Receptors, Formyl Peptide -- immunology KW - Phagocytes -- metabolism KW - Receptors, Lipoxin -- immunology KW - Alzheimer Disease -- metabolism KW - Alzheimer Disease -- immunology KW - Receptors, Lipoxin -- metabolism KW - Microglia -- pathology KW - Microglia -- metabolism KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67822532?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunologic+research&rft.atitle=Role+of+formyl+peptide+receptor-like+1+%28FPRL1%2FFPR2%29+in+mononuclear+phagocyte+responses+in+Alzheimer+disease.&rft.au=Iribarren%2C+Pablo%3BZhou%2C+Ye%3BHu%2C+Jinyue%3BLe%2C+Yingying%3BWang%2C+Ji+Ming&rft.aulast=Iribarren&rft.aufirst=Pablo&rft.date=2005-01-01&rft.volume=31&rft.issue=3&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Immunologic+research&rft.issn=0257277X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-02-27 N1 - Date created - 2005-05-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gemcitabine plus cisplatine and paclitaxel (GCP) in second-line treatment of germ cell tumors (GCT): a phase II study. AN - 67799540; 15875087 AB - The aim of the study was to determine the efficacy and toxicity of gemcitabine, cisplatin and paclitaxel (GCP) combination as a first salvage treatment of patients with relapsed GCT. Four courses of paclitaxel 175 mg/m(2) and cisplatin 50 mg/m(2), both on day 1, and gemcitabine 1000 mg/m(2), on days 1 and 8, every 3 weeks, were given to 12 consecutive patients who had failed standard 1st line treatment. Six patients (50%; 95% CI 21-79%) achieved favourable response and two of them are maintained 38+ and 29+ months. Median survival time was 16 months (range, 0.77-38+). All, but two patients had hematological toxicity Gr3-4 with infectious complication seen only in 6 courses of therapy. GCP is an active second-line combination regimen for relapsed GCTs with acceptable toxicity profile. However the results of this study did not show expected treatment efficacy and we raise the idea of cisplatin dosage relevance in this combination. JF - Neoplasma AU - Mardiak, J AU - Sálek, T AU - Sycová-Milá, Z AU - Obertová, J AU - Hlavatá, Z AU - Mego, M AU - Recková, M AU - Koza, I AD - Department of Medical Oncology, National Cancer Institute, 83310 Bratislava, Slovak Republic. jozef.mardiak@nou.sk Y1 - 2005 PY - 2005 DA - 2005 SP - 243 EP - 247 VL - 52 IS - 3 SN - 0028-2685, 0028-2685 KW - Deoxycytidine KW - 0W860991D6 KW - gemcitabine KW - B76N6SBZ8R KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Drug Administration Schedule KW - Humans KW - Adult KW - Treatment Outcome KW - Neoplasm Recurrence, Local -- blood KW - Male KW - Cisplatin -- administration & dosage KW - Testicular Neoplasms -- drug therapy KW - Testicular Neoplasms -- blood KW - Germinoma -- blood KW - Deoxycytidine -- analogs & derivatives KW - Deoxycytidine -- administration & dosage KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Germinoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67799540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Gemcitabine+plus+cisplatine+and+paclitaxel+%28GCP%29+in+second-line+treatment+of+germ+cell+tumors+%28GCT%29%3A+a+phase+II+study.&rft.au=Mardiak%2C+J%3BS%C3%A1lek%2C+T%3BSycov%C3%A1-Mil%C3%A1%2C+Z%3BObertov%C3%A1%2C+J%3BHlavat%C3%A1%2C+Z%3BMego%2C+M%3BReckov%C3%A1%2C+M%3BKoza%2C+I&rft.aulast=Mardiak&rft.aufirst=J&rft.date=2005-01-01&rft.volume=52&rft.issue=3&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-21 N1 - Date created - 2005-05-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The health of foreign workers in Italy. AN - 67787549; 15859193 AB - At the beginning of 2002, there were 1,600,000 foreign-born persons living in Italy; the majority from countries outside Europe. Those residing in the country for working purposes were 800,680. Italy's shift to a tertiary and service-oriented economy has considerably modified the working market, concentrating demand at two extremes: on one hand, a highly specialized workforce, and on the other, a totally unqualified, mobile, and flexible one, which includes most immigrants. JF - International journal of occupational and environmental health AU - Capacci, Fabio AU - Carnevale, Francesco AU - Gazzano, Noel AD - Unità Funzionale Prevenzione Igiene e Sicurezza nei Luoghi di Lavoro (PISLL) G. Pieraccini-Azienda Sanitaria di Firenze, Florence, Italy. fabio.capacci@asf.toscana.it PY - 2005 SP - 64 EP - 69 VL - 11 IS - 1 SN - 1077-3525, 1077-3525 KW - Index Medicus KW - Humans KW - Accidents, Occupational -- statistics & numerical data KW - Commerce KW - Italy -- epidemiology KW - Occupations KW - Human Rights KW - China -- ethnology KW - Occupational Health KW - Emigration and Immigration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67787549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+health+of+foreign+workers+in+Italy.&rft.au=Capacci%2C+Fabio%3BCarnevale%2C+Francesco%3BGazzano%2C+Noel&rft.aulast=Capacci&rft.aufirst=Fabio&rft.date=2005-01-01&rft.volume=11&rft.issue=1&rft.spage=64&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 - 2005-07-11 N1 - Date created - 2005-04-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amelioration of sodium arsenite-induced clastogenicity by tea extracts in Chinese hamster v79 cells. AN - 67739343; 15831085 AB - Since the early 1980s, an alarming problem of groundwater arsenic (As) contamination has devastated many districts of West Bengal in India. People drinking As-contaminated water have been suffering severe health problems such as hyperkeratosis, blackfoot disease, neuropathy, and cancer of various sites. DNA damage and genetic instability induced by the inorganic arsenicals present in water are thought to be prerequisites for the initiation of carcinogenesis. Many natural polyphenols, which are consumed through our daily diet, possess excellent cancer chemopreventive properties. Tea, a popular beverage worldwide and rich in polyphenols, has exhibited many health benefits. The present study was conducted to examine the anticlastogenic action of tea extracts (both green and black) against the As-induced chromosomal aberrations. We also evaluated the role of tea in inducing antioxidant enzymes such as superoxide dismutase and catalase to provide protection against the oxidative stress induced by As. Our results demonstrated that tea extracts, particularly Darjeeling tea extract, are effective in counteracting the clastogenicity (chromatid breaks, in particular) of the most potent form of As, sodium arsenite. The antioxidant function of tea in reducing clastogenicity may be partly due to the induction of phase II detoxification enymes, such as superoxide dismutase and catalase. Our results suggest that the use of tea may be an effective approach in combating the health crisis generated by As. JF - Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer AU - Sinha, Dona AU - Bhattacharya, Rathin K AU - Siddiqi, Maqsood AU - Roy, Madhumita AD - Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Kolkata 700 026, India. Y1 - 2005 PY - 2005 DA - 2005 SP - 129 EP - 140 VL - 24 IS - 2 SN - 0731-8898, 0731-8898 KW - Antimutagenic Agents KW - 0 KW - Antioxidants KW - Arsenites KW - Biflavonoids KW - Plant Extracts KW - Sodium Compounds KW - Tea KW - Water Pollutants, Chemical KW - theaflavin KW - 1IA46M0D13 KW - sodium arsenite KW - 48OVY2OC72 KW - Catechin KW - 8R1V1STN48 KW - epigallocatechin gallate KW - BQM438CTEL KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Index Medicus KW - Animals KW - Fibroblasts -- drug effects KW - Cricetulus KW - Superoxide Dismutase -- metabolism KW - Fibroblasts -- ultrastructure KW - Plant Extracts -- chemistry KW - Superoxide Dismutase -- biosynthesis KW - Catalase -- metabolism KW - Plant Extracts -- pharmacology KW - Catalase -- biosynthesis KW - Biflavonoids -- analysis KW - Camellia sinensis KW - Cell Line KW - Cricetinae KW - Chromosome Aberrations -- chemically induced KW - DNA Repair KW - Antimutagenic Agents -- pharmacology KW - Antioxidants -- pharmacology KW - Sodium Compounds -- antagonists & inhibitors KW - Catechin -- analogs & derivatives KW - Catechin -- analysis KW - Arsenites -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67739343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+pathology%2C+toxicology+and+oncology+%3A+official+organ+of+the+International+Society+for+Environmental+Toxicology+and+Cancer&rft.atitle=Amelioration+of+sodium+arsenite-induced+clastogenicity+by+tea+extracts+in+Chinese+hamster+v79+cells.&rft.au=Sinha%2C+Dona%3BBhattacharya%2C+Rathin+K%3BSiddiqi%2C+Maqsood%3BRoy%2C+Madhumita&rft.aulast=Sinha&rft.aufirst=Dona&rft.date=2005-01-01&rft.volume=24&rft.issue=2&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Journal+of+environmental+pathology%2C+toxicology+and+oncology+%3A+official+organ+of+the+International+Society+for+Environmental+Toxicology+and+Cancer&rft.issn=07318898&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-27 N1 - Date created - 2005-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlation of apoptosis with comet formation induced by tea polyphenols in human leukemia cells. AN - 67738882; 15831084 AB - Induction of apoptosis is an important approach to cancer control. Apart from morphological changes in cells, apoptosis is characterized by fragmentation of nuclear DNA. The characteristic DNA ladder formation that is observed on gel electrophoresis does not reflect the DNA breakdown in individual cells; contributions from small subpopulations are usually overlooked. On the other hand, alkaline comet assay as measured by single cell gel electrophoresis accurately measures DNA fragmentation at a single cell level. The comet assay was originally developed as a cytogenetic test to measure the genotoxicity of various chemicals. However, the comet image generated by an apoptotic cell is different from that obtained with a cell treated for a short time with a genotoxic agent. In the present study using human leukemic cells, typical apoptotic features such as morphological characteristics, FACS analysis, caspase activation, and expression of apoptosis-related genes as induced by tea polyphenols have been found to correlate with the comet tail formation. It is apparent from the high degree of correlation observed between the comet tail moment and each parameter of apoptosis that the comet assay can accurately reflect the measure of DNA fragmentation and, hence, can be used to detect a cell undergoing apoptosis. JF - Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer AU - Kundu, Trina AU - Bhattacharya, Rathin K AU - Siddiqi, Maqsood AU - Roy, Madhumita AD - Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, Kolkata 700 026, India. Y1 - 2005 PY - 2005 DA - 2005 SP - 115 EP - 128 VL - 24 IS - 2 SN - 0731-8898, 0731-8898 KW - Antioxidants KW - 0 KW - Biflavonoids KW - Flavonoids KW - Phenols KW - Polyphenols KW - Tea KW - theaflavin KW - 1IA46M0D13 KW - Catechin KW - 8R1V1STN48 KW - epigallocatechin gallate KW - BQM438CTEL KW - CASP3 protein, human KW - EC 3.4.22.- KW - CASP8 protein, human KW - Caspase 3 KW - Caspase 8 KW - Caspases KW - Index Medicus KW - HL-60 Cells KW - Humans KW - Biflavonoids -- pharmacology KW - Flow Cytometry KW - K562 Cells KW - Caspases -- metabolism KW - Comet Assay KW - Antioxidants -- pharmacology KW - Phenols -- pharmacology KW - Catechin -- analogs & derivatives KW - Apoptosis -- drug effects KW - Flavonoids -- pharmacology KW - Catechin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67738882?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+pathology%2C+toxicology+and+oncology+%3A+official+organ+of+the+International+Society+for+Environmental+Toxicology+and+Cancer&rft.atitle=Correlation+of+apoptosis+with+comet+formation+induced+by+tea+polyphenols+in+human+leukemia+cells.&rft.au=Kundu%2C+Trina%3BBhattacharya%2C+Rathin+K%3BSiddiqi%2C+Maqsood%3BRoy%2C+Madhumita&rft.aulast=Kundu&rft.aufirst=Trina&rft.date=2005-01-01&rft.volume=24&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Journal+of+environmental+pathology%2C+toxicology+and+oncology+%3A+official+organ+of+the+International+Society+for+Environmental+Toxicology+and+Cancer&rft.issn=07318898&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-27 N1 - Date created - 2005-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic alterations in brain tumors following 1,3-butadiene exposure in B6C3F1 mice. AN - 67721365; 15814359 AB - The nervous system of the B6C3F1 mouse has rarely been a target for chemical carcinogenesis in the National Toxicology Program (NTP) bioassays. However, 6 malignant gliomas and 2 neuroblastomas were observed in B6C3F1 mice exposed to 625 ppm 1,3-butadiene (NTP technical reports 288 and 434). These mouse brain tumors were evaluated with regard to the profile of genetic alterations that are observed in human brain tumors. Alterations in the p53 tumor suppressor gene were common. Missense mutations were observed in 3/6 malignant gliomas and 2/2 neuroblastomas and were associated with loss of heterozygosity. Most of the mutations occurred in exons 5-8 of the p53 gene and were G-->A transitions, and did not involve CpG sites. Loss of heterozygosity at the Ink4a/Arf gene locus was observed in 5/5 malignant gliomas and 1/1 neuroblastoma, while the PTEN(phosphatase and tensin homologue) gene locus was unaffected by deletions. One of 2 neuroblastomas had a mutation in codon 61 of H-ras, while H-ras mutations were not observed in the malignant gliomas examined. Only 1 brain tumor has been reported from control mice of over 500 NTP studies. This malignant glioma showed no evidence of alterations in the p53 gene or K- and H-ras mutations. It is likely that the specific genetic alterations observed were induced or selected for by 1,3-butadiene treatment that contributed to the development of mouse brain tumors. The observed findings are similar in part to the genetic alterations reported in human brain tumors. JF - Toxicologic pathology AU - Kim, Yongbaek AU - Hong, Hue-Hua L AU - Lachat, Yan AU - Clayton, Natasha P AU - Devereux, Theodora R AU - Melnick, Ronald L AU - Hegi, Monika E AU - Sills, Robert C AD - Laboratory of Experimental Pathology National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 307 EP - 312 VL - 33 IS - 3 SN - 0192-6233, 0192-6233 KW - Butadienes KW - 0 KW - Carcinogens KW - Codon KW - DNA, Neoplasm KW - Tumor Suppressor Protein p53 KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Exons KW - Mice KW - DNA, Neoplasm -- isolation & purification KW - Mutation, Missense KW - Gene Deletion KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Loss of Heterozygosity KW - Tumor Suppressor Protein p53 -- drug effects KW - DNA, Neoplasm -- genetics KW - Tumor Suppressor Protein p53 -- genetics KW - Immunohistochemistry KW - Female KW - Male KW - Neuroblastoma -- pathology KW - Brain Neoplasms -- pathology KW - Neuroblastoma -- genetics KW - Glioma -- pathology KW - Glioma -- chemically induced KW - Butadienes -- toxicity KW - Brain Neoplasms -- genetics KW - Carcinogens -- toxicity KW - Neuroblastoma -- chemically induced KW - Glioma -- genetics KW - Brain Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67721365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Genetic+alterations+in+brain+tumors+following+1%2C3-butadiene+exposure+in+B6C3F1+mice.&rft.au=Kim%2C+Yongbaek%3BHong%2C+Hue-Hua+L%3BLachat%2C+Yan%3BClayton%2C+Natasha+P%3BDevereux%2C+Theodora+R%3BMelnick%2C+Ronald+L%3BHegi%2C+Monika+E%3BSills%2C+Robert+C&rft.aulast=Kim&rft.aufirst=Yongbaek&rft.date=2005-01-01&rft.volume=33&rft.issue=3&rft.spage=307&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 - 2005-07-21 N1 - Date created - 2005-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High exposure to polycyclic aromatic hydrocarbons may contribute to high risk of esophageal cancer in northeastern Iran. AN - 67719851; 15816606 AB - The northeastern region of Iran has some of the highest rates of esophageal squamous cell carcinoma (ESCC) in the world. To investigate the role of polycyclic aromatic hydrocarbons (PAHs) in the etiology of ESCC in northeastern Iran, we measured urine 1-hydroxypyrene glucuronide (1-OHPG), a stable PAH metabolite, in 99 inhabitants of this area. The median urine 1-OHPG in participants of this study was 4.2 pmol/ml. Forty-two subjects (42%) had levels ranging from 1 to 5 pmol/ml, indicative of moderate PAH exposure, and 41 (41%) had levels above 5 pmol/ml, indicative of very high exposure. Further analysis showed that 1-OHPG levels were high in all subgroups of our study subjects, including both sexes, rural and urban dwellers, and smokers and non-smokers. Only 15% of the variance in 1-OHPG was explained by age, sex, residence, smoking, nass, or opium consumption. This pattern of PAH exposure parallels the ESCC incidence pattern seen in this area. We conclude that people in northeastern Iran are exposed to widespread and very high levels of PAH, largely from unknown sources, and this may contribute to the high rates of ESCC observed in this area. JF - Anticancer research AU - Kamangar, Farin AU - Strickland, Paul T AU - Pourshams, Akram AU - Malekzadeh, Reza AU - Boffetta, Paolo AU - Roth, Mark J AU - Abnet, Christian C AU - Saadatian-Elahi, Mitra AU - Rakhshani, Nasser AU - Brennan, Paul AU - Etemadi, Arash AU - Dawsey, Sanford M AD - Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 21218, USA. kamangaf@mail.nih.gov PY - 2005 SP - 425 EP - 428 VL - 25 IS - 1B SN - 0250-7005, 0250-7005 KW - 1-hydroxypyrene-glucuronide KW - 0 KW - Glucuronates KW - Polycyclic Aromatic Hydrocarbons KW - Pyrenes KW - Index Medicus KW - Risk KW - Iran KW - Humans KW - Glucuronates -- urine KW - Adult KW - Environmental Exposure KW - Aged KW - Pilot Projects KW - Middle Aged KW - Male KW - Female KW - Esophageal Neoplasms -- chemically induced KW - Carcinoma, Squamous Cell -- etiology KW - Carcinoma, Squamous Cell -- chemically induced KW - Polycyclic Aromatic Hydrocarbons -- adverse effects KW - Esophageal Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67719851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=High+exposure+to+polycyclic+aromatic+hydrocarbons+may+contribute+to+high+risk+of+esophageal+cancer+in+northeastern+Iran.&rft.au=Kamangar%2C+Farin%3BStrickland%2C+Paul+T%3BPourshams%2C+Akram%3BMalekzadeh%2C+Reza%3BBoffetta%2C+Paolo%3BRoth%2C+Mark+J%3BAbnet%2C+Christian+C%3BSaadatian-Elahi%2C+Mitra%3BRakhshani%2C+Nasser%3BBrennan%2C+Paul%3BEtemadi%2C+Arash%3BDawsey%2C+Sanford+M&rft.aulast=Kamangar&rft.aufirst=Farin&rft.date=2005-01-01&rft.volume=25&rft.issue=1B&rft.spage=425&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 - 2005-05-03 N1 - Date created - 2005-04-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New insights into functional aspects of liver morphology. AN - 67703183; 15805053 AB - The liver is structurally and functionally complex and has been considered second only to brain in its complexity. Many mysteries still exist in this heterogeneous tissue whose functional unit of the lobule has continued to stump morphologists for over 300 years. The primary lobule, proposed by Matsumoto in 1979, has been gaining acceptance as the functional unit of the liver over other conceptual views because it's based on vessel architecture and includes the classic lobule as a secondary feature. Although hepatocytes comprise almost 80% of the liver, there are at least another dozen cell types, many of which provide "cross-talk" and play important functional roles in the normal and diseased liver. The distribution and functional roles of all cells in the liver must be carefully considered in both the analysis and interpretation of research data, particularly data in the area of genomics and "phenotypic anchoring" of gene expression results. Discoveries regarding the functional heterogeneity of the various liver cell types, including hepatocytes, hepatic stellate cells, sinusoidal endothelia, and Kupffer cells, are providing new insights into our understanding of the development, prevention and treatment of liver disease. For example, functional differences along zonal patterns (centrilobular or periportal) have been demonstrated for sinusoidal endothelium, Kupffer cells, and hepatocytes and can explain the gradients and manifestations of disease observed within lobules. Intralobular gradients of bile uptake, glycogen depletion, glutamine synthetase, and carboxylesterase by hepatocytes; widened fenestrations in centrilobular sinusoidal lining cells; and differences in the components of centrilobular extracellular matrix or function of Kupffer cells have been demonstrated. Awareness of the complexities and heterogeneity of the liver will add to a greater understanding of liver function and disease processes that lead to toxicity, cancer, and other diseases. JF - Toxicologic pathology AU - Malarkey, David E AU - Johnson, Kennita AU - Ryan, Linda AU - Boorman, Gary AU - Maronpot, Robert R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. malarkey@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 27 EP - 34 VL - 33 IS - 1 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Imaging, Three-Dimensional KW - Animals KW - Humans KW - Transcription, Genetic KW - Liver -- anatomy & histology KW - Liver -- cytology KW - Liver -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67703183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=New+insights+into+functional+aspects+of+liver+morphology.&rft.au=Malarkey%2C+David+E%3BJohnson%2C+Kennita%3BRyan%2C+Linda%3BBoorman%2C+Gary%3BMaronpot%2C+Robert+R&rft.aulast=Malarkey&rft.aufirst=David&rft.date=2005-01-01&rft.volume=33&rft.issue=1&rft.spage=27&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 - 2005-06-06 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Olfactory epithelial metaplasia and hyperplasia in female Harlan Sprague-Dawley rats following chronic treatment with polychlorinated biphenyls. AN - 67702425; 15805076 AB - The National Toxicology Program recently completed a series of studies to evaluate the relative potency for toxicity and carcinogenicity of several polyhalogenated aromatic hydrocarbons including dioxin-like compounds (DLCs) and polychlorinated biphenyls. Female Sprague-Dawley rats were administered by gavage for up to 2 years with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); 3,3',4,4',5-pentachlorobiphenyl (PCB126); 2,3,4,7,8-pentachlorodibenzofuran (PeCDF); 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153); a tertiary mixture of TCDD, PCB126, and PeCDF; a binary mixture of PCB126 and 153; or a binary mixture of PCB126 and 2,3',4,4',5-pentachlorobiphenyl (PCB118); control animals received corn oil-acetone vehicle (99:1) alone. Nasal epithelial changes were observed only in animals exposed for 2 years to the higher doses of the binary mixtures of PCB126 + PCB153 (1000 ng/kg and 1000 microg/kg) and PCB126 + PCB118 (216 and 360 ng TCDD equivalents/kg). In both studies, the changes were of the same nonneoplastic nature, localized to nasal sections II and III located, respectively, at the level of the incisive papilla anterior to the first palatial ridge (section II) and through the middle of the second molar teeth (section III). The changes consisted of hyperplasia of the respiratory epithelium (level II) and metaplasia of olfactory epithelium to respiratory epithelium with further hyperplasia of the metaplastic respiratory epithelium (levels II and III). Variable amounts of acute inflammatory exudate appeared within the lumen of the nasal cavity, overlying the affected epithelium. Occasionally, the inflammation eroded through the skull and into the adjacent olfactory bulbs. JF - Toxicologic pathology AU - Nyska, Abraham AU - Yoshizawa, Katsuhiko AU - Jokinen, Micheal P AU - Brix, Amy E AU - Sells, Donald M AU - Wyde, Michael E AU - Orzech, Denise P AU - Kissling, Grace E AU - Walker, Nigel J AD - Laboratory of Experimental Pathology National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709-9998, USA. nyska@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 371 EP - 377 VL - 33 IS - 3 SN - 0192-6233, 0192-6233 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Rats KW - Molecular Structure KW - Administration, Oral KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Female KW - Hyperplasia -- pathology KW - Hyperplasia -- chemically induced KW - Polychlorinated Biphenyls -- toxicity KW - Polychlorinated Biphenyls -- chemistry KW - Toxicity Tests, Chronic KW - Olfactory Mucosa -- pathology KW - Metaplasia -- pathology KW - Metaplasia -- chemically induced KW - Polychlorinated Biphenyls -- administration & dosage KW - Olfactory Mucosa -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67702425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Olfactory+epithelial+metaplasia+and+hyperplasia+in+female+Harlan+Sprague-Dawley+rats+following+chronic+treatment+with+polychlorinated+biphenyls.&rft.au=Nyska%2C+Abraham%3BYoshizawa%2C+Katsuhiko%3BJokinen%2C+Micheal+P%3BBrix%2C+Amy+E%3BSells%2C+Donald+M%3BWyde%2C+Michael+E%3BOrzech%2C+Denise+P%3BKissling%2C+Grace+E%3BWalker%2C+Nigel+J&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=2005-01-01&rft.volume=33&rft.issue=3&rft.spage=371&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 - 2005-07-21 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular mechanisms of hepatocarcinogenesis in transgenic mouse models of liver cancer. AN - 67702276; 15805070 AB - Overexpression of c-myc and transforming growth factor-alpha (TGF-alpha) has been frequently observed in human hepatocellular carcinoma (HCC),suggesting a pivotal role played by these protooncogenes in liver oncogenesis. In order to investigate the molecular events underlying human hepatic malignant transformation, we have generated c-myc and c-myc/ TGF-alpha transgenic mice that are prone to liver cancer. These transgenic mice develop HCCs with different incidence, kinetics and histopathological features. Indeed, co-expression of c-myc and TGF-alpha transgenes results in a dramatic synergistic effect on liver tumor development when compared with respective single transgenic lines, including a shorter latency period and a more aggressive phenotype. The more malignant histopathological features characteristic of c-myc/ TGF-alpha HCCs are the result of the increased proliferation and reduced apoptosis in this model of liver cancer when compared with single parental lines. Accordingly, c-myc and c-myc/l TGF-alpha transgenic mice display a different molecular pathogenesis of HCC. Importantly, the genetic and molecular mechanisms that are involved in c-myc and c-myc/ TGF-alpha liver cancer development are major oncogenic events in human hepatocarcinogenesis, indicating that these mouse models represent a useful tool to dissect and elucidate the molecular basis of human HCC. JF - Toxicologic pathology AU - Calvisi, Diego F 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 - 2005 PY - 2005 DA - 2005 SP - 181 EP - 184 VL - 33 IS - 1 SN - 0192-6233, 0192-6233 KW - Proto-Oncogene Proteins c-myc KW - 0 KW - Transforming Growth Factor alpha KW - Index Medicus KW - Animals KW - Transgenes KW - Mice KW - Mice, Transgenic KW - Transforming Growth Factor alpha -- genetics KW - Molecular Biology KW - Liver Neoplasms, Experimental -- etiology KW - Models, Genetic KW - Proto-Oncogene Proteins c-myc -- genetics KW - Proto-Oncogene Proteins c-myc -- metabolism KW - Transforming Growth Factor alpha -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67702276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+mechanisms+of+hepatocarcinogenesis+in+transgenic+mouse+models+of+liver+cancer.&rft.au=Calvisi%2C+Diego+F%3BThorgeirsson%2C+Snorri+S&rft.aulast=Calvisi&rft.aufirst=Diego&rft.date=2005-01-01&rft.volume=33&rft.issue=1&rft.spage=181&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 - 2005-06-06 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional profiling of the left and median liver lobes of male f344/n rats following exposure to acetaminophen. AN - 67702225; 15805062 AB - The liver is a common organ for transcriptional profiling because of its role in xenobiotic metabolism and because hepatotoxicity is a common response to chemical exposure. To explore the impact that sampling different lobes may have on transcriptional profiling experiments we have examined and compared gene expression profiles of the left and median lobes of livers from male F344 rats exposed to toxic and nontoxic doses of acetaminophen. Transcript profiling using micorarrays revealed clear differences in the response of the left and median liver lobes of F344 rats to acetaminophen exposure both at low doses as well as doses that caused hepatotoxicity. Differences were found in the total number of differentially expressed genes in the left and median lobes, the number and identity of genes that were differentially expressed uniquely only in the left or median lobe, and in the patterns of gene expression. While it is not possible to generalize these results to compounds other than acetaminophen or other strains of rat, these results highlight the potential impact of sampling differences on the interpretation of gene expression profiles in the liver. JF - Toxicologic pathology AU - Irwin, Richard D AU - Parker, Joel S AU - Lobenhofer, Edward K AU - Burka, Leo T AU - Blackshear, Pamela E AU - Vallant, Molly K AU - Lebetkin, Edward H AU - Gerken, Diane F AU - Boorman, Gary A AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. irwin@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 111 EP - 117 VL - 33 IS - 1 SN - 0192-6233, 0192-6233 KW - Analgesics, Non-Narcotic KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Necrosis KW - Oligonucleotide Array Sequence Analysis KW - Dose-Response Relationship, Drug KW - Male KW - Inflammation KW - Liver -- anatomy & histology KW - Gene Expression Profiling KW - Liver -- pathology KW - Liver -- drug effects KW - Analgesics, Non-Narcotic -- toxicity KW - Liver -- metabolism KW - Acetaminophen -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67702225?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transcriptional+profiling+of+the+left+and+median+liver+lobes+of+male+f344%2Fn+rats+following+exposure+to+acetaminophen.&rft.au=Irwin%2C+Richard+D%3BParker%2C+Joel+S%3BLobenhofer%2C+Edward+K%3BBurka%2C+Leo+T%3BBlackshear%2C+Pamela+E%3BVallant%2C+Molly+K%3BLebetkin%2C+Edward+H%3BGerken%2C+Diane+F%3BBoorman%2C+Gary+A&rft.aulast=Irwin&rft.aufirst=Richard&rft.date=2005-01-01&rft.volume=33&rft.issue=1&rft.spage=111&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 - 2005-06-06 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microarray data analysis of mouse neoplasia. AN - 67700322; 15805064 AB - Microarray gene expression analysis offers great promise to help us understand the molecular events of experimental carcinogenesis, but have such promises been fulfilled? Studies of gene expression profiles of rodent are being published and demonstrate that yes, indeed, gene array data is furthering our understanding of tumor biology. Recent studies have identified differentially expressed genes in rodent mammary, colon, lung, and liver tumors. Although relatively few genes on the rodent arrays have been fully characterized, information has been generated to better identify signatures of histologic type and grade, understand invasion and metastasis, identify candidate biomarkers of early development, identify gene networks in carcinogenesis, understand responses to therapy, and decifer overlap with molecular events in human cancers. Data from mouse lung, mammary gland, and liver tumor studies are reviewed as examples of how to approach and interpret gene array data. Methods of gene array data analysis were also applied for discovery of genes involved in the regression of mouse liver tumors induced by chlordane, a nongenotoxic murine hepatocarcinogen. Promises are beginning to be fulfilled and it is clear that pathologists and toxicologists, in collaboration with molecular biologists, bioinformatists,and other scientists are making great strides in the design, analysis, and interpretation of microarray data for cancer studies. JF - Toxicologic pathology AU - Malarkey, David E AU - Parker, Joel S AU - Turman, Coral A AU - Scott, Allyson M AU - Paules, Richard S AU - Collins, Jennifer AU - Maronpot, Robert R AD - Laboratory of Experimental Pathology, Research Triangle Park, North Carolina 27709, USA. malarkey@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 127 EP - 135 VL - 33 IS - 1 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Humans KW - Neoplasms -- pathology KW - Microarray Analysis KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67700322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Microarray+data+analysis+of+mouse+neoplasia.&rft.au=Malarkey%2C+David+E%3BParker%2C+Joel+S%3BTurman%2C+Coral+A%3BScott%2C+Allyson+M%3BPaules%2C+Richard+S%3BCollins%2C+Jennifer%3BMaronpot%2C+Robert+R&rft.aulast=Malarkey&rft.aufirst=David&rft.date=2005-01-01&rft.volume=33&rft.issue=1&rft.spage=127&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 - 2005-06-06 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Variation in the hepatic gene expression in individual male Fischer rats. AN - 67700285; 15805061 AB - A new tool beginning to have wider application in toxicology studies is transcript profiling using microarrays. Microarrays provide an opportunity to directly compare transcript populations in the tissues of chemical-exposed and unexposed animals. While several studies have addressed variation between microarray platforms and between different laboratories, much less effort has been directed toward individual animal differences especially among control animals where RNA samples are usually pooled. Estimation of the variation in gene expression in tissues from untreated animals is essential for the recognition and interpretation of subtle changes associated with chemical exposure. In this study hepatic gene expression as well as standard toxicological parameters were evaluated in 24 rats receiving vehicle only in 2 independent experiments. Unsupervised clustering demonstrated some individual variation but supervised clustering suggested that differentially expressed genes were generally random. The level of hepatic gene expression under carefully controlled study conditions is less than 1.5-fold for most genes. The impact of individual animal variability on microarray data can be minimized through experimental design. JF - Toxicologic pathology AU - Boorman, Gary A AU - Irwin, Richard D AU - Vallant, Molly K AU - Gerken, Diane K AU - Lobenhofer, Edward K AU - Hejtmancik, Milton R AU - Hurban, Patrick AU - Brys, April M AU - Travlos, Greg S AU - Parker, Joel S AU - Portier, Christopher J AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. boorman@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 102 EP - 110 VL - 33 IS - 1 SN - 0192-6233, 0192-6233 KW - RNA, Messenger KW - 0 KW - Index Medicus KW - Rats KW - Gene Expression Profiling KW - Animals KW - Rats, Inbred F344 KW - RNA, Messenger -- metabolism KW - Oligonucleotide Array Sequence Analysis KW - Male KW - Genetic Variation KW - Gene Expression KW - Liver -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67700285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Variation+in+the+hepatic+gene+expression+in+individual+male+Fischer+rats.&rft.au=Boorman%2C+Gary+A%3BIrwin%2C+Richard+D%3BVallant%2C+Molly+K%3BGerken%2C+Diane+K%3BLobenhofer%2C+Edward+K%3BHejtmancik%2C+Milton+R%3BHurban%2C+Patrick%3BBrys%2C+April+M%3BTravlos%2C+Greg+S%3BParker%2C+Joel+S%3BPortier%2C+Christopher+J&rft.aulast=Boorman&rft.aufirst=Gary&rft.date=2005-01-01&rft.volume=33&rft.issue=1&rft.spage=102&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 - 2005-06-06 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strategies for quitting among non-treatment-seeking marijuana smokers. AN - 67573413; 15804875 AB - This study examines self-reported quitting strategies used by adult, non-treatment-seeking marijuana smokers. Sixty-five subjects rated the use and effectiveness of thirteen strategies on a self-developed instrument, the Marijuana Quit Questionnaire. The strategies clustered into three categories/factors, whether grouped by principal components analysis, mean helpfulness rating, or frequency of endorsement: Change Environment, Seeking Organized/Professional Help, and Social Support. Changing one's environment was rated as most helpful while seeking help from professionals was the least helpful. Clinicians are likely to see marijuana users in their practice and should be proactive in offering assistance, incorporating the strategies reported here into treatment plans for their marijuana-using patients. JF - The American journal on addictions AU - Boyd, Susan J AU - Tashkin, Donald P AU - Huestis, Marilyn A AU - Heishman, Stephen J AU - Dermand, John C AU - Simmons, Michael S AU - Gorelick, David A AD - Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD 21224, USA. PY - 2005 SP - 35 EP - 42 VL - 14 IS - 1 SN - 1055-0496, 1055-0496 KW - Index Medicus KW - Environment KW - Self Care KW - Humans KW - Principal Component Analysis KW - Adult KW - Health Behavior KW - Social Support KW - Male KW - Female KW - Motivation KW - Marijuana Smoking -- psychology KW - Marijuana Abuse -- rehabilitation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67573413?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Strategies+for+quitting+among+non-treatment-seeking+marijuana+smokers.&rft.au=Boyd%2C+Susan+J%3BTashkin%2C+Donald+P%3BHuestis%2C+Marilyn+A%3BHeishman%2C+Stephen+J%3BDermand%2C+John+C%3BSimmons%2C+Michael+S%3BGorelick%2C+David+A&rft.aulast=Boyd&rft.aufirst=Susan&rft.date=2005-01-01&rft.volume=14&rft.issue=1&rft.spage=35&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 - 2005-06-14 N1 - Date created - 2005-04-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention of febrile neutropenia in cancer patients by probiotic strain Enterococcus faecium M-74. Pilot study phase I. AN - 67568195; 15800715 AB - Febrile neutropenia (FN) remains a potentially life-threatening complication of anticancer chemotherapy. Bacterial translocation via intestinal mucosa is a significant mechanism of FN development. Competitive inhibition of bowel colonization by pathogenic microorganisms by lactic acid bacteria could be a useful prevention of FN. The aim of the study was the evaluation of dose and safety of probiotic strain Enterococcus faecium M-74 enriched with organic selenium in patients with solid and hematological malignancies. Eleven (9 M/2F) patients were included in the study. In the first phase six patients with germ cell tumors treated by chemotherapy were included. They received prophylaxis by nonpathogenic strain E. faecium M-74 during 2 cycles of chemotherapy. The planned daily dose was 6 x 10(9) bacteria. Regarding the insufficient colonization of the gut, the dose was further increased up to 18 x 10(9) tid. After safety evaluation, five patients were included with relapse of acute leukemia. In patients with germ cell cancer, severe neutropenia G3/4 was noted in 10 of 12 cycles of chemotherapy. The febrile episode was not observed in any of the patients. The gut colonization by enterococci reaches 10(6) CFU/g stool. In 5 patients with acute leukemia during 127 days of severe neutropenia 12 febrile episodes occurred. There was not noted any febrile episode or infection provoked by the tested strain. Tolerance of therapy was excellent without significant undesirable effects. Optimal dose was assessed and safety of probiotic strain was evaluated in neutropenic patients with solid, or hematological malignancies. Based on these results we plan phase II study to evaluate the effectiveness of this strain in FN prophylaxis. JF - Neoplasma AU - Mego, M AU - Ebringer, L AU - Drgona, L AU - Mardiak, J AU - Trupl, J AU - Greksak, R AU - Nemova, I AU - Oravcova, E AU - Zajac, V AU - Koza, I AD - Department of Medical Oncology, National Cancer Institute, 83310 Bratislava, Slovak Republic. michal.mego@nou.sk Y1 - 2005 PY - 2005 DA - 2005 SP - 159 EP - 164 VL - 52 IS - 2 SN - 0028-2685, 0028-2685 KW - Antineoplastic Agents KW - 0 KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Administration, Oral KW - Leukemia -- drug therapy KW - Humans KW - Adult KW - Intestinal Mucosa -- microbiology KW - Middle Aged KW - Male KW - Female KW - Fever -- chemically induced KW - Enterococcus faecium -- growth & development KW - Probiotics KW - Fever -- prevention & control KW - Neutropenia -- prevention & control KW - Neutropenia -- chemically induced KW - Neoplasms, Germ Cell and Embryonal -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67568195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Prevention+of+febrile+neutropenia+in+cancer+patients+by+probiotic+strain+Enterococcus+faecium+M-74.+Pilot+study+phase+I.&rft.au=Mego%2C+M%3BEbringer%2C+L%3BDrgona%2C+L%3BMardiak%2C+J%3BTrupl%2C+J%3BGreksak%2C+R%3BNemova%2C+I%3BOravcova%2C+E%3BZajac%2C+V%3BKoza%2C+I&rft.aulast=Mego&rft.aufirst=M&rft.date=2005-01-01&rft.volume=52&rft.issue=2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-21 N1 - Date created - 2005-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protracted lithium treatment protects against the ER stress elicited by thapsigargin in rat PC12 cells: roles of intracellular calcium, GRP78 and Bcl-2. AN - 67525943; 15668729 AB - We investigated the cytoprotective effects of lithium, the mood-stabilizer, on thapsigargin-induced stress on the endoplasmic reticulum (ER) in rat PC12 cells. Protracted lithium pretreatment of PC12 cells elicited cytoprotection against thapsigargin-induced cytotoxicity. Lithium protection was concurrent with inhibition of thapsigargin-induced intracellular calcium increase and with elevated expression of the molecular chaperone GRP78. Moreover, lithium pretreatment upregulated the antiapoptotic protein Bcl-2, and blocked Bcl-2 downregulation elicited by thapsigargin. Prior to the induction of GRP78, lithium treatment alone increased the expression of c-Fos whose induction by ER stress is necessary for GRP78 induction. Curcumin, an inhibitor of transcription factor AP-1, blocked lithium cytoprotection against thapsigargin cytotoxicity. Thus, the induction of GRP78 and Bcl-2, and activation of AP-1 likely contribute to lithium-induced protection against cytotoxicity resulting from ER stress. Additionally, thapsigargin-induced cytotoxicity was suppressed by pretreatment with another mood-stabilizer, valproate, indicating that cytoprotection against ER stress is a common action of mood-stabilizing drugs. JF - The pharmacogenomics journal AU - Hiroi, T AU - Wei, H AU - Hough, C AU - Leeds, P AU - Chuang, D-M AD - Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1363, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 102 EP - 111 VL - 5 IS - 2 SN - 1470-269X, 1470-269X KW - Enzyme Inhibitors KW - 0 KW - Heat-Shock Proteins KW - Hspa5 protein, rat KW - Molecular Chaperones KW - Neuroprotective Agents KW - Proto-Oncogene Proteins c-bcl-2 KW - Proto-Oncogene Proteins c-fos KW - RNA, Messenger KW - Transcription Factor AP-1 KW - Valproic Acid KW - 614OI1Z5WI KW - Thapsigargin KW - 67526-95-8 KW - Lithium KW - 9FN79X2M3F KW - Calcium-Transporting ATPases KW - EC 3.6.3.8 KW - Curcumin KW - IT942ZTH98 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Transcription Factor AP-1 -- antagonists & inhibitors KW - Electrophoretic Mobility Shift Assay KW - Calcium-Transporting ATPases -- antagonists & inhibitors KW - Reverse Transcriptase Polymerase Chain Reaction KW - Transcription Factor AP-1 -- genetics KW - RNA, Messenger -- biosynthesis KW - Curcumin -- pharmacology KW - Valproic Acid -- pharmacology KW - Rats KW - Blotting, Western KW - Cell Survival -- drug effects KW - PC12 Cells KW - Proto-Oncogene Proteins c-fos -- biosynthesis KW - Endoplasmic Reticulum -- enzymology KW - Endoplasmic Reticulum -- metabolism KW - Molecular Chaperones -- physiology KW - Enzyme Inhibitors -- toxicity KW - Proto-Oncogene Proteins c-bcl-2 -- physiology KW - Heat-Shock Proteins -- physiology KW - Thapsigargin -- toxicity KW - Thapsigargin -- antagonists & inhibitors KW - Calcium -- metabolism KW - Calcium -- physiology KW - Endoplasmic Reticulum -- drug effects KW - Lithium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67525943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+pharmacogenomics+journal&rft.atitle=Protracted+lithium+treatment+protects+against+the+ER+stress+elicited+by+thapsigargin+in+rat+PC12+cells%3A+roles+of+intracellular+calcium%2C+GRP78+and+Bcl-2.&rft.au=Hiroi%2C+T%3BWei%2C+H%3BHough%2C+C%3BLeeds%2C+P%3BChuang%2C+D-M&rft.aulast=Hiroi&rft.aufirst=T&rft.date=2005-01-01&rft.volume=5&rft.issue=2&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=The+pharmacogenomics+journal&rft.issn=1470269X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-12 N1 - Date created - 2005-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recent marijuana blunt smoking impacts carbon monoxide as a measure of adolescent tobacco abstinence. AN - 67522983; 15770886 AB - Adolescent tobacco smokers have a higher prevalence of marijuana (MJ) smoking than adolescents who do not smoke tobacco. As part of an adolescent smoking cessation trial, we examined whether MJ smoking, and specifically "blunt" (gutted cigars filled with MJ) smoking, elevated participants' likelihood of a false indication of cigarette smoking on the basis of breath carbon monoxide (CO) testing. Using clinical data from 37 adolescents (mean age 15.1+/-1.4 years, 78% female) who participated in a smoking-cessation trial in Baltimore between 1999 and 2002, and who on at least one occasion, reported abstinence from tobacco smoking for at least 7 days, we analyzed 146 cigarette-abstinent-visit exhaled CO concentrations classified into blunt occasions (12 participants, 33 visits), nonblunt MJ occasions (seven participants, 20 visits), and non-MJ occasions (27 paricipants, 93 visits). Repeated-measures logistic regression revealed that blunt occasions were associated with CO > or = 8 ppm, compared to nonblunt occasions (p = 0.013). Blunt occasions also tended to be associated with the more youth-appropriate cutoff CO > or = 6 ppm, compared to non-MJ occasions (p =0.054). Blunt smoking impacted the interpretation of measures of exhaled CO for tobacco cessation. JF - Substance use & misuse AU - Moolchan, Eric T AU - Zimmerman, Darin AU - Sehnert, Shelley S AU - Zimmerman, Debra AU - Huestis, Marilyn A AU - Epstein, David H AD - Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA. emoolcha@intra.nida.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 231 EP - 240 VL - 40 IS - 2 SN - 1082-6084, 1082-6084 KW - Carbon Monoxide KW - 7U1EE4V452 KW - Index Medicus KW - Humans KW - Surveys and Questionnaires KW - Adolescent KW - Male KW - Female KW - Cognitive Therapy -- methods KW - Breath Tests KW - Carbon Monoxide -- analysis KW - Tobacco Use Disorder -- therapy KW - Smoking Cessation -- methods KW - Tobacco Use Disorder -- prevention & control KW - Marijuana Abuse -- epidemiology KW - Smoking -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67522983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Substance+use+%26+misuse&rft.atitle=Recent+marijuana+blunt+smoking+impacts+carbon+monoxide+as+a+measure+of+adolescent+tobacco+abstinence.&rft.au=Moolchan%2C+Eric+T%3BZimmerman%2C+Darin%3BSehnert%2C+Shelley+S%3BZimmerman%2C+Debra%3BHuestis%2C+Marilyn+A%3BEpstein%2C+David+H&rft.aulast=Moolchan&rft.aufirst=Eric&rft.date=2005-01-01&rft.volume=40&rft.issue=2&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Substance+use+%26+misuse&rft.issn=10826084&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-10 N1 - Date created - 2005-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactive oxygen species and lung tumorigenesis by mutant K-ras: a working hypothesis. AN - 67512632; 15765920 AB - Wild-type K-ras is tumor suppressive in mouse lung, but mutant K-ras is actively oncogenic. Thus, the mutant protein must acquire new, dominant protumorigenic properties. Generation of reactive oxygen species could be one such property. The authors demonstrate increased peroxides in lung epithelial cells (E10)-transfected with mutant hK-ras(va112). An associated increase in DNA damage (comet assay) correlates with increased cyclooxygenase-2 protein. This DNA damage is completely abrogated by a specific cyclooxygenase-2 inhibitor (SC58125) or by a cell-permeable modified catalase. Literature is reviewed regarding generation of reactive oxygen and cyclooxygenase-2 induction by ras, cyclooxygenase-2 release of DNA-damaging reactive oxygen, and involvement of cyclooxygenase-2 and reactive oxygen in lung cancer JF - Experimental lung research AU - Maciag, Anna AU - Anderson, Lucy M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. PY - 2005 SP - 83 EP - 104 VL - 31 IS - 1 SN - 0190-2148, 0190-2148 KW - Membrane Proteins KW - 0 KW - Reactive Oxygen Species KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Animals KW - DNA Damage KW - Humans KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Genes, ras KW - Gene Expression Regulation, Neoplastic KW - Reactive Oxygen Species -- metabolism KW - Adenocarcinoma -- metabolism KW - Mutation -- genetics KW - Lung Neoplasms -- genetics KW - Adenocarcinoma -- genetics KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67512632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Reactive+oxygen+species+and+lung+tumorigenesis+by+mutant+K-ras%3A+a+working+hypothesis.&rft.au=Maciag%2C+Anna%3BAnderson%2C+Lucy+M&rft.aulast=Maciag&rft.aufirst=Anna&rft.date=2005-01-01&rft.volume=31&rft.issue=1&rft.spage=83&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 - 2005-04-28 N1 - Date created - 2005-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mouse models incorporating alterations in the major tumor suppressor genes P53 and P16: their use in screening for potential carcinogens, developing further relevant mouse models, and screening for potential chemopreventive and chemotherapetutic agents. AN - 67511338; 15765922 AB - This review is primarily a follow up to an initial review on this subject that the authors published 4 years ago [Lubet et al., Exp Lung Res. 2000; 581-593]. The present review gives a brief discussion of certain background points and rationale for development of these specific models, which had been presented in greater detail in the earlier article. In that initial article the authors identified the potential use of mutant mice in screening for carcinogens as well as preventive or therapeutic agents, discussed the relevance of the dominant-negative P53 mutation, as contrasted with knockout P53 mice, and briefly discussed the pros and cons of mice with a germline mutation in tumor suppressor genes in developing mouse models. The primary objective of the present review is to describe more recent studies using mice the dominant-negative P53 mutation as well as to introduce studies with mice with a heterozygous knockout of the P16/Ink4A ARF locus. JF - Experimental lung research AU - Lubet, Ronald AU - Wang, Yian AU - Zhang, Zhongqiu AU - You, Ming AD - Chemoprevention Agent Development Research Group, National Cancer Institute, Rockville, MD 20892, USA. lubetr@mail.nih.gov PY - 2005 SP - 117 EP - 133 VL - 31 IS - 1 SN - 0190-2148, 0190-2148 KW - Anticarcinogenic Agents KW - 0 KW - Index Medicus KW - Animals KW - Mice, Mutant Strains KW - Carcinogenicity Tests -- methods KW - Lung Neoplasms -- therapy KW - Lung Neoplasms -- genetics KW - Mice KW - Adenocarcinoma -- therapy KW - Adenocarcinoma -- genetics KW - Drug Screening Assays, Antitumor -- methods KW - Lung Neoplasms -- pathology KW - Adenocarcinoma -- pathology KW - Anticarcinogenic Agents -- therapeutic use KW - Genes, p53 KW - Disease Models, Animal KW - Chemoprevention KW - Anticarcinogenic Agents -- classification KW - Genes, p16 KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67511338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mouse+models+incorporating+alterations+in+the+major+tumor+suppressor+genes+P53+and+P16%3A+their+use+in+screening+for+potential+carcinogens%2C+developing+further+relevant+mouse+models%2C+and+screening+for+potential+chemopreventive+and+chemotherapetutic+agents.&rft.au=Lubet%2C+Ronald%3BWang%2C+Yian%3BZhang%2C+Zhongqiu%3BYou%2C+Ming&rft.aulast=Lubet&rft.aufirst=Ronald&rft.date=2005-01-01&rft.volume=31&rft.issue=1&rft.spage=117&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 - 2005-04-28 N1 - Date created - 2005-03-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - From context-dependence of mutations to molecular mechanisms of mutagenesis. AN - 67506657; 15759646 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 nucleotide sequence context of mutational hotspots is a fingerprint of interactions between DNA and repair/replication/modification enzymes, and the analysis of hotspot context provides evidence of such interactions. The hotspots might also reflect structural and functional features of the respective DNA sequences and provide information about natural selection. We discuss analysis of 8-oxoguanine-induced mutations in pro- and eukaryotic genes, polymorphic positions in the human mitochondrial DNA and mutations in the HIV-1 retrovirus. Comparative analysis of 8-oxoguanine-induced mutations and spontaneous mutation spectra suggested that a substantial fraction of spontaneous A x T-->C x T mutations is caused by 8-oxoGTP in nucleotide pools. In the case of human mitochondrial DNA, significant differences between molecular mechanisms of mutations in hypervariable segments and coding part of DNA were detected. Analysis of mutations in the HIV-1 retrovirus suggested a complex interplay between molecular mechanisms of mutagenesis and natural selection. JF - Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing AU - Rogozin, Igor B AU - Malyarchuk, Boris A AU - Pavlov, Youri I AU - Milanesi, Luciano AD - National Center for Biotechnology Information NLM, National Institutes of Health, Bethesda, MD 20894, USA. rogozin@ncbi.nlm.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 409 EP - 420 SN - 2335-6936, 2335-6936 KW - DNA Primers KW - 0 KW - DNA, Mitochondrial KW - DNA, Viral KW - Mutagens KW - DNA KW - 9007-49-2 KW - Index Medicus KW - DNA Repair -- genetics KW - HIV-1 -- genetics KW - DNA Replication -- genetics KW - Base Sequence KW - Models, Genetic KW - Humans KW - DNA -- genetics KW - Molecular Sequence Data KW - Templates, Genetic KW - DNA, Viral -- genetics KW - DNA, Mitochondrial -- genetics KW - Mutation KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67506657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pacific+Symposium+on+Biocomputing.+Pacific+Symposium+on+Biocomputing&rft.atitle=From+context-dependence+of+mutations+to+molecular+mechanisms+of+mutagenesis.&rft.au=Rogozin%2C+Igor+B%3BMalyarchuk%2C+Boris+A%3BPavlov%2C+Youri+I%3BMilanesi%2C+Luciano&rft.aulast=Rogozin&rft.aufirst=Igor&rft.date=2005-01-01&rft.volume=&rft.issue=&rft.spage=409&rft.isbn=&rft.btitle=&rft.title=Pacific+Symposium+on+Biocomputing.+Pacific+Symposium+on+Biocomputing&rft.issn=23356936&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-11 N1 - Date created - 2005-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucocorticoid-induced osteoporosis: from basic mechanisms to clinical aspects. AN - 67501143; 15756049 AB - Glucocorticoid (GC)-induced osteoporosis (GCOP) is the most common cause of osteoporosis in adults aged 20-45 years as well as the most common cause of iatrogenic osteoporosis. GC excess, either endogenous or exogenous, induces bone loss in 30-50% of cases. Indeed, bone loss leading to fractures is perhaps the most incapacitating, sometimes partially irreversible, complication of GC therapy. Nevertheless, GCOP is often underdiagnosed and left untreated. The following article provides an update on the cellular and molecular mechanisms implicated in the pathophysiology of GC-induced bone loss, as well as some guidelines on diagnostic, preventive and therapeutic strategies for this medical condition, in an effort to promote a better knowledge and greater awareness of GCOP by both the patient and the physician. JF - Neuroimmunomodulation AU - Alesci, Salvatore AU - De Martino, Massimo U AU - Ilias, Ioannis AU - Gold, Philip W AU - Chrousos, George P AD - Clinical Neuroendocrinology Branch, National Institute of Mental Health, Bethesda, MD 20892-1284, USA. alescisa@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 1 EP - 19 VL - 12 IS - 1 SN - 1021-7401, 1021-7401 KW - Glucocorticoids KW - 0 KW - Growth Substances KW - Index Medicus KW - Osteoblasts -- metabolism KW - Osteoblasts -- drug effects KW - Animals KW - Osteogenesis -- physiology KW - Humans KW - Osteoclasts -- metabolism KW - Osteoclasts -- drug effects KW - Osteogenesis -- drug effects KW - Growth Substances -- metabolism KW - Glucocorticoids -- metabolism KW - Bone and Bones -- physiopathology KW - Bone and Bones -- drug effects KW - Glucocorticoids -- adverse effects KW - Bone and Bones -- metabolism KW - Osteoporosis -- therapy KW - Osteoporosis -- physiopathology KW - Osteoporosis -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67501143?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroimmunomodulation&rft.atitle=Glucocorticoid-induced+osteoporosis%3A+from+basic+mechanisms+to+clinical+aspects.&rft.au=Alesci%2C+Salvatore%3BDe+Martino%2C+Massimo+U%3BIlias%2C+Ioannis%3BGold%2C+Philip+W%3BChrousos%2C+George+P&rft.aulast=Alesci&rft.aufirst=Salvatore&rft.date=2005-01-01&rft.volume=12&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Neuroimmunomodulation&rft.issn=10217401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-30 N1 - Date created - 2005-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A clinical and biological overview of gastrointestinal stromal tumors. AN - 67487926; 15750190 AB - In the last few years a body of knowledge has been generated on the molecular basis of gastrointestinal stromal tumors (GIST). These mesenchymal tumors are characterized by the expression of KIT protein and because they have an activating mutation in a class III receptor tyrosine kinase gene (KIT or PDGFRA). Several KIT-activating mutations, which are largely responsible for the development of this tumor, promote cell survival, proliferation, and migration through different pathways such as MAPK p42/44, AKT, S6K, STAT1, and STAT3. Likewise, gene-activating mutations in the gene PDGFRalpha which codes for the receptor tyrosine kinase, Platelet-derived growth factor receptor alpha have been identified in GIST lacking KIT mutations. This means that KIT and PDGFRalpha mutations appear to be alternative and mutually exclusive oncogenic pathways for GIST development. These tumors may occur anywhere along the gastrointestinal tract (GI). The most frequently involved sites are stomach and small intestine. They are typically chemo- and radioresistant. The discovery of a specific inhibitor of this tyrosine kinase, imatinib mesylate, has radically changed the prognosis of patients with unresectable disease. Only 4 yr after the first patient was successfully treated with imatinib, multiple phase II and III trials have been published and, currently, imatinib mesylate is the only effective systemic treatment available of these tumors. Response rates are approximately 70-90% with acceptable toxicity. GIST are the first model of a solid tumor efficiently treated with a molecular-targeted agent. This review summarizes the clinical and biological aspects of this unique neoplasm. JF - Medical oncology (Northwood, London, England) AU - Candelaria, Myrna AU - de la Garza, Jaime AU - Duenas-Gonzalez, Alfonso AD - Division of Clinical Research, National Cancer Institute, Mexico City. mcandelariah@incan.edu.mx Y1 - 2005 PY - 2005 DA - 2005 SP - 1 EP - 10 VL - 22 IS - 1 SN - 1357-0560, 1357-0560 KW - Benzamides KW - 0 KW - Piperazines KW - Pyrimidines KW - Imatinib Mesylate KW - 8A1O1M485B KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Proto-Oncogene Proteins c-kit KW - EC 2.7.10.1 KW - Index Medicus KW - Pyrimidines -- therapeutic use KW - Positron-Emission Tomography KW - Piperazines -- therapeutic use KW - Phosphatidylinositol 3-Kinases -- physiology KW - Humans KW - Prognosis KW - Mutation KW - Proto-Oncogene Proteins c-kit -- genetics KW - Gastrointestinal Neoplasms -- drug therapy KW - Gastrointestinal Neoplasms -- diagnosis KW - Stromal Cells -- pathology KW - Gastrointestinal Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67487926?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+oncology+%28Northwood%2C+London%2C+England%29&rft.atitle=A+clinical+and+biological+overview+of+gastrointestinal+stromal+tumors.&rft.au=Candelaria%2C+Myrna%3Bde+la+Garza%2C+Jaime%3BDuenas-Gonzalez%2C+Alfonso&rft.aulast=Candelaria&rft.aufirst=Myrna&rft.date=2005-01-01&rft.volume=22&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Medical+oncology+%28Northwood%2C+London%2C+England%29&rft.issn=13570560&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-08 N1 - Date created - 2005-03-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduction of hematotoxicity and augmentation of antitumor efficacy of cyclophosphamide by dopamine. AN - 67477497; 15739030 AB - Modulatory effects of dopamine (DA) on hematotoxicity and antitumor efficacy of cyclophosphamide (CY) were studied in Swiss mice bearing transplantable Ehrlich ascites carcinoma (EAC). DA was administered i.p. at a dose of 50 mg/kg/day for 5 consecutive days beginning day 3 after tumor transplantation. CY (200 mg/kg i.p.) was injected 24 hour after completion of DA treatment. DA pretreatment reduced the suppressive effects of CY on hemoglobin, RBC, total WBC, neutrophil, platelet, and bone marrow nucleated cell counts. Likewise, DA partially prevented the CY-induced fall in pluripotent (CFU-S12) and lineage-specific stem cells for granulocytes (CFU-C) in bone marrow. Moreover, mice receiving a combination of DA and CY illustrated greater reduction in tumor volume, viable tumor cell count and mitotic index along with upregulation of tumor cell apoptosis than CY-only group. As a result, the former group demonstrated prolonged hosts survival. Thus, DA protected to a great extent the hematopoietic cells of tumor bearing hosts from the suppressive action of CY and concomitantly augmented its antitumor efficacy resulting in improved hosts survival. JF - Neoplasma AU - Lakshmi, C AU - Deb, C AU - Ray, C AU - Ray, M R AD - Experimental Hematology Unit, Chittaranjan National Cancer Institute, Kolkata 700026, India. Y1 - 2005 PY - 2005 DA - 2005 SP - 68 EP - 73 VL - 52 IS - 1 SN - 0028-2685, 0028-2685 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Cardiotonic Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Injections, Intraperitoneal KW - Animals KW - Drug Interactions KW - Apoptosis KW - Mitotic Index KW - Mice KW - Up-Regulation KW - Cell Proliferation KW - Male KW - Survival Analysis KW - Cell Survival KW - Dopamine -- pharmacology KW - Cardiotonic Agents -- administration & dosage KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Cardiotonic Agents -- pharmacology KW - Hematopoietic Stem Cells -- drug effects KW - Dopamine -- administration & dosage KW - Cyclophosphamide -- pharmacology KW - Cyclophosphamide -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67477497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neoplasma&rft.atitle=Reduction+of+hematotoxicity+and+augmentation+of+antitumor+efficacy+of+cyclophosphamide+by+dopamine.&rft.au=Lakshmi%2C+C%3BDeb%2C+C%3BRay%2C+C%3BRay%2C+M+R&rft.aulast=Lakshmi&rft.aufirst=C&rft.date=2005-01-01&rft.volume=52&rft.issue=1&rft.spage=68&rft.isbn=&rft.btitle=&rft.title=Neoplasma&rft.issn=00282685&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-03 N1 - Date created - 2005-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phloxine B phototoxicity: a mechanistic study using HaCaT keratinocytes. AN - 67472016; 15473832 AB - Phloxine B (PhB) (2',4',5',7'-tetrabromo-4,5,6,7-tetrachlorofluorescein; D&C Red No. 28) is a red dye found in drugs, cosmetics and foods; it is also currently being evaluated as a phototoxin for the potential control of fruit flies. Previous studies have shown that PhB is an efficient photosensitizer of damage to cellular membranes; thus, exposure of the skin to the dye and sunlight or artificial light may result in phototoxicity. Therefore, we have studied the phototoxicity of PhB and its structural analogue 2',7'-dichlorofluorescein (DCF) to HaCaT keratinocytes. Anaerobic visible irradiation (>400 nm) of PhB generated a semiquinone type radical, as detected by direct electron paramagnetic resonance. Aerobic visible irradiation of a reaction mixture containing PhB, the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and nicotinamide adenine dinucleotide (reduced) generated a superoxide dismutase-sensitive DMPO/O(2)(.-) adduct. Irradiation of PhB and DCF in D(2)O generated singlet oxygen with quantum yields of 0.59 and 0.06, respectively. PhB was much more phototoxic than DCF when cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Visible irradiation of HaCaT keratinocytes in the presence of PhB (5 micro M) resulted in a 90% decrease in cell viability. 3beta-Hydroxy-5alpha-cholest-6-ene-5-hydroperoxide, a singlet oxygen photoproduct of cholesterol, was isolated from HaCaT keratinocytes irradiated in the presence of PhB. Furthermore, PhB phototoxicity was inhibited by histidine and cysteine, quenchers of singlet oxygen. PhB (0.5 microM) and light irradiation also resulted in DNA damage, as measured by the Comet assay. The phototoxicity mechanism of PhB most probably initially involves a Type-II reaction with free radicals playing a minor role. However, secondary oxidative species such as radicals generated as a result of lipid peroxidation may serve to further promote oxidative damage. Our findings suggest that concern is warranted about the use of this dye in cosmetic products, as a food additive and in insecticidal sprays. JF - Photochemistry and photobiology AU - Inbaraj, Johnson J AU - Kukielczak, Barbara M AU - Chignell, Colin F AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. PY - 2005 SP - 81 EP - 88 VL - 81 IS - 1 SN - 0031-8655, 0031-8655 KW - Singlet Oxygen KW - 17778-80-2 KW - Eosine I Bluish KW - OMS4XQD1T0 KW - Index Medicus KW - Comet Assay KW - Spectrometry, Fluorescence KW - DNA Damage KW - Humans KW - Electron Spin Resonance Spectroscopy KW - Cell Line, Transformed KW - Lipid Peroxidation KW - Eosine I Bluish -- toxicity KW - Keratinocytes -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67472016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phloxine+B+phototoxicity%3A+a+mechanistic+study+using+HaCaT+keratinocytes.&rft.au=Inbaraj%2C+Johnson+J%3BKukielczak%2C+Barbara+M%3BChignell%2C+Colin+F&rft.aulast=Inbaraj&rft.aufirst=Johnson&rft.date=2005-01-01&rft.volume=81&rft.issue=1&rft.spage=81&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 - 2005-06-30 N1 - Date created - 2005-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ATP-dependent chromatin remodeling complexes and their role in nuclear receptor-dependent transcription in vivo. AN - 67461218; 15727808 AB - Nuclear receptors (NRs) are ligand-dependent transcription factors that mediate transcription of target genes in chromatin. Modulation of chromatin structure plays an important part in the NR-mediated transcription process. ATP-dependent chromatin remodeling complexes have been shown to be intimately involved in NR-mediated transcription. In this review, we examine the role of chromatin remodeling complexes in facilitating the recruitment of coregulators and basal transcription factors. In addition, the role of subunit specificity within the chromatin remodeling complexes, the complexes' influence on remodeling activity, and complexes' recruitment to the NR-responsive promoters are discussed. JF - Vitamins and hormones AU - Aoyagi, Sayura AU - Trotter, Kevin W AU - Archer, Trevor K AD - Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 281 EP - 307 VL - 70 SN - 0083-6729, 0083-6729 KW - Chromatin KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Chromatin -- metabolism KW - Chromatin -- chemistry KW - Transcription, Genetic KW - Chromatin -- ultrastructure KW - Adenosine Triphosphate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67461218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vitamins+and+hormones&rft.atitle=ATP-dependent+chromatin+remodeling+complexes+and+their+role+in+nuclear+receptor-dependent+transcription+in+vivo.&rft.au=Aoyagi%2C+Sayura%3BTrotter%2C+Kevin+W%3BArcher%2C+Trevor+K&rft.aulast=Aoyagi&rft.aufirst=Sayura&rft.date=2005-01-01&rft.volume=70&rft.issue=&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Vitamins+and+hormones&rft.issn=00836729&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-21 N1 - Date created - 2005-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Co-occurrence of DSM-IV personality disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. AN - 67436982; 15714187 AB - The objective of this study was to determine the co-occurrence of 7 of the 10 Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision ( DSM-IV-TR ) personality disorders (PDs) in the US population. Face-to-face interviews were conducted with 43 093 respondents in the National Institute on Alcohol Abuse and Alcoholism's 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative survey of the US population. Odds ratios were calculated to determine associations among PDs. All associations among PDs were positive and statistically significant. PDs were significantly associated with other PDs within the same cluster, in addition to being highly associated with PDs of other DSM-IV PD clusters. Co-occurrence between DSM-IV PDs is pervasive in the US general population. Future research is needed on the creation of dimensional representations of DSM-IV PDs as an adjunct to categorical diagnoses. JF - Comprehensive psychiatry AU - Grant, Bridget F AU - Stinson, Frederick S AU - Dawson, Deborah A AU - Chou, S Patricia AU - Ruan, W June AD - Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD 20892-9304, USA. bgrant@wilco.niaaa.nih.gov PY - 2005 SP - 1 EP - 5 VL - 46 IS - 1 SN - 0010-440X, 0010-440X KW - Index Medicus KW - Reproducibility of Results KW - Humans KW - Comorbidity KW - Population Surveillance -- methods KW - Epidemiologic Studies KW - Adult KW - Sampling Studies KW - Adolescent KW - United States -- epidemiology KW - Cluster Analysis KW - Female KW - Male KW - Substance-Related Disorders -- epidemiology KW - Prevalence KW - Personality Disorders -- epidemiology KW - Alcoholism -- epidemiology KW - Surveys and Questionnaires KW - Diagnostic and Statistical Manual of Mental Disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67436982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Comprehensive+psychiatry&rft.atitle=Co-occurrence+of+DSM-IV+personality+disorders+in+the+United+States%3A+results+from+the+National+Epidemiologic+Survey+on+Alcohol+and+Related+Conditions.&rft.au=Grant%2C+Bridget+F%3BStinson%2C+Frederick+S%3BDawson%2C+Deborah+A%3BChou%2C+S+Patricia%3BRuan%2C+W+June&rft.aulast=Grant&rft.aufirst=Bridget&rft.date=2005-01-01&rft.volume=46&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Comprehensive+psychiatry&rft.issn=0010440X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-19 N1 - Date created - 2005-02-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arsenic-induced micronuclei formation in mammalian cells and its counteraction by tea. AN - 67435137; 15715508 AB - The Gangetic plain of West Bengal, India, has been engulfed by a disastrous environmental calamity of arsenic contamination of the ground water. Chronic arsenic toxicity caused by drinking arsenic-contaminated water has been one of the worst health hazards gradually affecting nine districts of West Bengal since the early 1980s. Over and above hyperpigmentation and keratosis,weakness, burning sensation of the eyes, swelling of the legs, liver fibrosis, chronic lung disease, gangrene of the toes, neuropathy, and skin cancer are other manifestations. Induction of cancer is frequently associated with DNA damage, changes in ploidy of cells, and non-random chromosome aberrations. Counteraction of these genotoxic and cytogenetic abnormalities with natural dietary polyphenols could be a useful strategy to combat arsenic-induced DNA damage and thereby cancer. A review of the literature showed that it is the antioxidant property of tea polyphenols that affords protection against various types of cancer. The present study was conducted to investigate whether the extracts of green tea and black tea (Darjeeling and Assam) as well as their polyphenols could ameliorate this arsenic-induced genotoxicity. The normal mammalian cell culture derived from male Chinese hamster lung fibroblast cells (V79) was used as the test system to assess the genotoxicity by micronucleus assay. The results showed that both green tea and black tea extracts have equal potential in modulating the arsenic-induced genotoxicity. This effect was perhaps induced by the constituent polyphenols present in green and black tea. In addition, the repair activity of the damaged cells was enhanced when treated with these tea extracts and their polyphenols. Thus, tea and its polyphenols may have a promising role in counteracting the devastating effects of arsenic. JF - Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer AU - Sinha, Dona AU - Roy, Madhumita AU - Siddiqi, Maqsood AU - Bhattacharya, Rathin K AD - Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, Kolkata, India. Y1 - 2005 PY - 2005 DA - 2005 SP - 45 EP - 56 VL - 24 IS - 1 SN - 0731-8898, 0731-8898 KW - Antioxidants KW - 0 KW - Arsenates KW - Arsenites KW - Plant Extracts KW - Sodium Compounds KW - Tea KW - sodium arsenite KW - 48OVY2OC72 KW - sodium arsenate KW - 7631-89-2 KW - Cacodylic Acid KW - AJ2HL7EU8K KW - Index Medicus KW - Plant Extracts -- pharmacology KW - Animals KW - Micronucleus Tests KW - Cricetulus KW - Male KW - Cell Line KW - Cricetinae KW - Micronuclei, Chromosome-Defective -- drug effects KW - Antioxidants -- pharmacology KW - Micronuclei, Chromosome-Defective -- chemically induced KW - Arsenites -- toxicity KW - Sodium Compounds -- toxicity KW - Arsenates -- toxicity KW - Cacodylic Acid -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67435137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+pathology%2C+toxicology+and+oncology+%3A+official+organ+of+the+International+Society+for+Environmental+Toxicology+and+Cancer&rft.atitle=Arsenic-induced+micronuclei+formation+in+mammalian+cells+and+its+counteraction+by+tea.&rft.au=Sinha%2C+Dona%3BRoy%2C+Madhumita%3BSiddiqi%2C+Maqsood%3BBhattacharya%2C+Rathin+K&rft.aulast=Sinha&rft.aufirst=Dona&rft.date=2005-01-01&rft.volume=24&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Journal+of+environmental+pathology%2C+toxicology+and+oncology+%3A+official+organ+of+the+International+Society+for+Environmental+Toxicology+and+Cancer&rft.issn=07318898&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-28 N1 - Date created - 2005-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhancement of amphetamine-induced locomotor response in rats on different regimens of diet restriction and 2-deoxy-D-glucose treatment. AN - 67425825; 15708486 AB - Diet restriction (DR) in rodents increases lifespan, reduces age-related disease and pathology, increases stress responses, and maintains better function later into life compared with conventional ad libitum (AL) feeding. We have been investigating different DR regimens and also DR mimetics that stimulate stress response pathways that are activated by DR. By inhibiting glycolysis, feeding or injection of 2-deoxy-D-glucose (2DG) has been proposed as a DR mimetic and has been shown to provide neuroprotection. In the current study, we examined whether 2DG treatment produces behavioral changes similar to those observed in DR rats following stimulation of the dopaminergic (DA) system by D-amphetamine (AMPH). Male Fischer 344 rats were maintained on different dietary regimens: 40% daily DR (40% DR); every-other-day feeding (EOD); or AL with some groups provided food containing 0.4% 2DG or injected i.p. with 2DG. In addition, we examined the persistence of effects of DR or 2DG feeding after switching rats to AL. When locomotor activity was assessed at different time points following initiation of dietary treatments, we noted that the enhancement of AMPH-induced locomotor responses emerged earlier in DR rats than observed in 2DG fed rats, but 40% DR and EOD rats responded in a similar manner. Enhanced locomotor responses persisted in 2DG fed rats even when returned to normal diet for 1 month and in the case of DR rats even after 2 months of AL feeding. Three weeks of 2DG injections also enhanced AMPH response, but this effect was transient. The most important finding was that 2DG did not affect body weight or diet intake yet had effects similar to DR. Thus, 2DG appears to activate DA pathways in the same direction as DR does but without the necessity of reducing caloric intake. JF - Neuroscience AU - Mamczarz, J AU - Bowker, J L AU - Duffy, K AU - Zhu, M AU - Hagepanos, A AU - Ingram, D K AD - Behavioral Neuroscience Section, Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 451 EP - 464 VL - 131 IS - 2 SN - 0306-4522, 0306-4522 KW - Deoxyglucose KW - 9G2MP84A8W KW - Amphetamine KW - CK833KGX7E KW - Index Medicus KW - Rats KW - Eating -- drug effects KW - Eating -- physiology KW - Animals KW - Rats, Inbred F344 KW - Dose-Response Relationship, Drug KW - Body Weight -- drug effects KW - Body Weight -- physiology KW - Drug Synergism KW - Caloric Restriction -- methods KW - Motor Activity -- physiology KW - Motor Activity -- drug effects KW - Deoxyglucose -- pharmacology KW - Amphetamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67425825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Enhancement+of+amphetamine-induced+locomotor+response+in+rats+on+different+regimens+of+diet+restriction+and+2-deoxy-D-glucose+treatment.&rft.au=Mamczarz%2C+J%3BBowker%2C+J+L%3BDuffy%2C+K%3BZhu%2C+M%3BHagepanos%2C+A%3BIngram%2C+D+K&rft.aulast=Mamczarz&rft.aufirst=J&rft.date=2005-01-01&rft.volume=131&rft.issue=2&rft.spage=451&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-03 N1 - Date created - 2005-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct binding of estradiol enhances Slack (sequence like a calcium-activated potassium channel) channels' activity. AN - 67421992; 15708472 AB - 17Beta-estradiol (E2) is a major neuroregulator, exerting both genomic and non-genomic actions. E2 regulation of Slack (sequence like a calcium-activated potassium channel) potassium channels has not been identified in the CNS. We demonstrate E2-induced activation of Slack channels, which display a unitary conductance of about 60 pS, are inhibited by intracellular calcium, and are abundantly expressed in the nervous system. In lipid bilayers derived from rat cortical neuronal membranes, E2 increases Slack open probability and appears to decrease channel inactivation. Additionally, E2 binds to the Slack channel and activates outward currents in human embryonic kidney-293 cells that express Slack channels but not classical estrogen receptors (i.e. ERalpha or ERbeta). Neither E2-induced activation nor the binding intensity of E2 to the Slack channel is blocked by tamoxifen, an ER antagonist/agonist. Thus, E2 activates a potassium channel, Slack, through a non-traditional membrane binding site, adding to known non-genomic mechanisms by which E2 exerts pharmacological and toxicological effects in the CNS. JF - Neuroscience AU - Zhang, L AU - Sukhareva, M AU - Barker, J L AU - Maric, D AU - Hao, Y AU - Chang, Y H AU - Ma, W AU - O'Shaughnessy, T AU - Rubinow, D R AD - Behavioral Endocrinology Branch, NIMH/NIH, Building 10, Room 65340, MSC 1276, Bethesda, MD 20892-1276, USA. lezhang@usuhs.mil Y1 - 2005 PY - 2005 DA - 2005 SP - 275 EP - 282 VL - 131 IS - 2 SN - 0306-4522, 0306-4522 KW - Nerve Tissue Proteins KW - 0 KW - Potassium Channels KW - Slack protein, rat KW - Estradiol KW - 4TI98Z838E KW - Index Medicus KW - Protein Binding -- physiology KW - Animals KW - Neurons -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Line KW - Potassium Channels -- metabolism KW - Potassium Channels -- genetics KW - Nerve Tissue Proteins -- metabolism KW - Nerve Tissue Proteins -- genetics KW - Estradiol -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67421992?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Direct+binding+of+estradiol+enhances+Slack+%28sequence+like+a+calcium-activated+potassium+channel%29+channels%27+activity.&rft.au=Zhang%2C+L%3BSukhareva%2C+M%3BBarker%2C+J+L%3BMaric%2C+D%3BHao%2C+Y%3BChang%2C+Y+H%3BMa%2C+W%3BO%27Shaughnessy%2C+T%3BRubinow%2C+D+R&rft.aulast=Zhang&rft.aufirst=L&rft.date=2005-01-01&rft.volume=131&rft.issue=2&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-03 N1 - Date created - 2005-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53: traffic cop at the crossroads of DNA repair and recombination. AN - 67395943; 15688066 AB - p53 mutants that lack DNA-binding activities, and therefore, transcriptional activities, are among the most common mutations in human cancer. Recently, a new role for p53 has come to light, as the tumour suppressor also functions in DNA repair and recombination. In cooperation with its function in transcription, the transcription-independent roles of p53 contribute to the control and efficiency of DNA repair and recombination. JF - Nature reviews. Molecular cell biology AU - Sengupta, Sagar AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Building 37, Room 3068, Bethesda, Maryland, 20892-4255, USA. Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 44 EP - 55 VL - 6 IS - 1 SN - 1471-0072, 1471-0072 KW - DNA-Binding Proteins KW - 0 KW - Tumor Suppressor Protein p53 KW - XPC protein, human KW - 156533-34-5 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - RECQL protein, human KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - Index Medicus KW - Animals KW - DNA Helicases -- physiology KW - Adenosine Triphosphatases -- physiology KW - Humans KW - DNA-Binding Proteins -- physiology KW - DNA Repair -- physiology KW - Tumor Suppressor Protein p53 -- physiology KW - Recombination, Genetic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67395943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Molecular+cell+biology&rft.atitle=p53%3A+traffic+cop+at+the+crossroads+of+DNA+repair+and+recombination.&rft.au=Sengupta%2C+Sagar%3BHarris%2C+Curtis+C&rft.aulast=Sengupta&rft.aufirst=Sagar&rft.date=2005-01-01&rft.volume=6&rft.issue=1&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Molecular+cell+biology&rft.issn=14710072&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-02 N1 - Date created - 2005-02-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutamate enhances survival and proliferation of neural progenitors derived from the subventricular zone. AN - 67392426; 15680691 AB - Extracellular glutamate levels increase as a consequence of perinatal hypoxia/ischemia, causing the death of neurons and oligodendrocytes. Precursors in the subventricular zone (SVZ) also die following perinatal hypoxia/ischemia; therefore we hypothesized that glutamate would stimulate the death of neural precursors. Here we demonstrate using calcium imaging that SVZ derived neural stem/progenitor cells respond to both ionotropic and metabotropic excitatory amino acids. Therefore, we tested the effects of high levels of glutamate receptor agonists on the proliferation, survival, and differentiation of SVZ derived neural stem/progenitor cells in vitro. We show that high levels of glutamate, up to 1 mM, are not toxic to neural precursor cultures. In fact, stimulation of either the kainate receptor or group 2 metabotropic glutamate receptors (group 2 mGluR) reduces basal levels of apoptosis and increases neural precursor proliferation. Furthermore, group 2 mGluR activation expands the number of multipotent progenitor cells present in these cultures while maintaining equivalent mature cell production. We conclude that the glutamate released following perinatal hypoxia/ischemia may act to acutely promote the proliferation of multipotent precursors in the subventricular zone. JF - Neuroscience AU - Brazel, C Y AU - Nuñez, J L AU - Yang, Z AU - Levison, S W AD - Stem Cell Biology Unit, Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Center, Baltimore, MD 21224, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 55 EP - 65 VL - 131 IS - 1 SN - 0306-4522, 0306-4522 KW - Gdnf protein, rat KW - 0 KW - Glial Cell Line-Derived Neurotrophic Factor KW - Nerve Growth Factors KW - Receptors, Kainic Acid KW - Receptors, Metabotropic Glutamate KW - metabotropic glutamate receptor 2 KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Glutamic Acid KW - 3KX376GY7L KW - Nerve Growth Factor KW - 9061-61-4 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - L-Lactate Dehydrogenase -- analysis KW - Fibroblast Growth Factor 2 -- genetics KW - Receptors, Metabotropic Glutamate -- drug effects KW - Receptors, Metabotropic Glutamate -- physiology KW - Receptors, Kainic Acid -- physiology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Calcium -- metabolism KW - Rats KW - Animals, Newborn KW - Necrosis KW - Nerve Growth Factors -- genetics KW - Rats, Wistar KW - Nerve Growth Factor -- genetics KW - Stem Cells -- drug effects KW - Oligodendroglia -- drug effects KW - Stem Cells -- cytology KW - Cell Survival -- drug effects KW - Neurons -- drug effects KW - Neurons -- cytology KW - Cell Division -- drug effects KW - Glutamic Acid -- pharmacology KW - Oligodendroglia -- cytology KW - Cerebral Ventricles -- drug effects KW - Cerebral Ventricles -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67392426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Glutamate+enhances+survival+and+proliferation+of+neural+progenitors+derived+from+the+subventricular+zone.&rft.au=Brazel%2C+C+Y%3BNu%C3%B1ez%2C+J+L%3BYang%2C+Z%3BLevison%2C+S+W&rft.aulast=Brazel&rft.aufirst=C&rft.date=2005-01-01&rft.volume=131&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-25 N1 - Date created - 2005-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling. AN - 67387526; 15671525 AB - Constitutive activation of the NF-kappaB pathway is required for survival of the activated B cell-like (ABC) subgroup of diffuse large B-cell lymphoma (DLBCL). Here we show that a small molecule IkappaB kinase (IKK) inhibitor, PS-1145, and related compounds are toxic for ABC DLBCL cell lines but not for cell lines derived from the other prevalent form of DLBCL, germinal center B cell-like DLBCL. Treatment of ABC lines with these inhibitors rapidly induced a series of gene expression changes that were attributable to cessation of constitutive IKK activity, similar to changes induced by acute expression of genetic inhibitors of NF-kappaB, confirming the effectiveness and specificity of this compound. Before cell death, inhibition of IKK also induced features of apoptosis and an arrest in the G1 phase of the cell cycle. To test further the specificity of this toxicity, an inducible form of NF-kappaB was created by fusing the p65 NF-kappaB subunit with the ligand-binding domain of the estrogen receptor (p65-ERD). In the presence of tamoxifen, p65-ERD reversed the toxicity of IKK inhibition and restored expression of many NF-kappaB target genes. Another subgroup of DLBCL, primary mediastinal B-cell lymphoma (PMBL), also expresses NF-kappaB target genes, and treatment of a PMBL cell line with an IKK inhibitor was toxic and induced gene expression changes of a distinct group of NF-kappaB target genes. These studies validate the NF-kappaB pathway as a promising therapeutic target in ABC DLBCL, PMBL, and other lymphomas that depend on the activity of NF-kappaB for survival and proliferation. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Lam, Lloyd T AU - Davis, R Eric AU - Pierce, Jackie AU - Hepperle, Michael AU - Xu, Yajun AU - Hottelet, Maria AU - Nong, Yuhua AU - Wen, Danyi AU - Adams, Julian AU - Dang, Lenny AU - Staudt, Louis M AD - Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA. Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - 28 EP - 40 VL - 11 IS - 1 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Carbolines KW - Enzyme Inhibitors KW - Heterocyclic Compounds, 3-Ring KW - MLX105 KW - NF-kappa B KW - PS1145 KW - Pyridines KW - Receptors, Estrogen KW - Tamoxifen KW - 094ZI81Y45 KW - L-Lactate Dehydrogenase KW - EC 1.1.1.27 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CHUK protein, human KW - EC 2.7.11.10 KW - I-kappa B Kinase KW - IKBKB protein, human KW - IKBKE protein, human KW - Index Medicus KW - Apoptosis KW - Humans KW - Cell Proliferation KW - Cell Survival KW - Genes, Dominant KW - Down-Regulation KW - Inhibitory Concentration 50 KW - Cell Cycle KW - Time Factors KW - L-Lactate Dehydrogenase -- metabolism KW - Leukocytes, Mononuclear -- cytology KW - Tamoxifen -- pharmacology KW - Dose-Response Relationship, Drug KW - Cell Line, Tumor KW - Receptors, Estrogen -- metabolism KW - Heterocyclic Compounds, 3-Ring -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Up-Regulation KW - Carbolines -- pharmacology KW - Protein Structure, Tertiary KW - Antineoplastic Agents -- pharmacology KW - Pyridines -- pharmacology KW - Cell Line KW - NF-kappa B -- metabolism KW - Gene Expression Regulation, Neoplastic KW - Protein-Serine-Threonine Kinases -- chemistry KW - Lymphoma, B-Cell -- drug therapy KW - Protein-Serine-Threonine Kinases -- metabolism KW - Lymphoma, Large B-Cell, Diffuse -- drug therapy KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67387526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Small+molecule+inhibitors+of+IkappaB+kinase+are+selectively+toxic+for+subgroups+of+diffuse+large+B-cell+lymphoma+defined+by+gene+expression+profiling.&rft.au=Lam%2C+Lloyd+T%3BDavis%2C+R+Eric%3BPierce%2C+Jackie%3BHepperle%2C+Michael%3BXu%2C+Yajun%3BHottelet%2C+Maria%3BNong%2C+Yuhua%3BWen%2C+Danyi%3BAdams%2C+Julian%3BDang%2C+Lenny%3BStaudt%2C+Louis+M&rft.aulast=Lam&rft.aufirst=Lloyd&rft.date=2005-01-01&rft.volume=11&rft.issue=1&rft.spage=28&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 - 2005-06-28 N1 - Date created - 2005-01-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Cancer Res. 2005 Jan 1;11(1):2-6 [15671521] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer. AN - 67381134; 15658101 AB - Convection-enhanced delivery (CED) is increasingly used to distribute therapeutic agents to locations in the central nervous system. The optimal application of convective distribution of various agents requires the development of imaging tracers to monitor CED in vivo in real time. The authors examined the safety and utility of an iodine-based low-molecular-weight surrogate tracer for computerized tomography (CT) scanning during CED. Various volumes (total volume range 90-150 microl) of iopamidol (MW 777 D) were delivered to the cerebral white matter of four primates (Macaca mulatta) by using CED. The distribution of this imaging tracer was determined by in vivo real-time and postinfusion CT scanning (< or = 5 days after infusion [one animal]) as well as by quantitative autoradiography (14C-sucrose [all animals] and 14C-dextran [one animal]), and compared with a mathematical model. Clinical observation (- 5 months) and histopathological analyses were used to evaluate the safety and toxicity of the tracer delivery. Real-time CT scanning of the tracer during infusion revealed a clearly definable region of perfusion. The volume of distribution (Vd) increased linearly (r2 = 0.97) with an increasing volume of infusion (V.). The overall Vd/Vi ratio was 4.1+/-0.7 (mean+/-standard deviation) and the distribution of infusate was homogeneous. Quantitative autoradiography confirmed the accuracy of the imaged distribution for a small (sucrose, MW 359 D) and a large (dextran, MW 70 kD) molecule. The distribution of the infusate was identifiable up to 72 hours after infusion. There was no clinical or histopathological evidence of toxicity in any animal. Real-time in vivo CT scanning of CED of iopamidol appears to be safe, feasible, and suitable for monitoring convective delivery of drugs with certain features and low infusion volumes. JF - Journal of neurosurgery AU - Croteau, David AU - Walbridge, Stuart AU - Morrison, Paul F AU - Butman, John A AU - Vortmeyer, Alexander O AU - Johnson, Dennis 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 - 2005/01// PY - 2005 DA - January 2005 SP - 90 EP - 97 VL - 102 IS - 1 SN - 0022-3085, 0022-3085 KW - Contrast Media KW - 0 KW - Iopamidol KW - JR13W81H44 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Osmolar Concentration KW - Magnetic Resonance Imaging KW - Convection KW - Animals KW - Rats, Sprague-Dawley KW - Feasibility Studies KW - Tomography, X-Ray Computed KW - Macaca mulatta KW - Tissue Distribution KW - Autoradiography -- methods KW - Time Factors KW - Male KW - Iopamidol -- pharmacokinetics KW - Contrast Media -- pharmacokinetics KW - Brain -- anatomy & histology KW - Contrast Media -- administration & dosage KW - Brain -- metabolism KW - Iopamidol -- administration & dosage KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67381134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Real-time+in+vivo+imaging+of+the+convective+distribution+of+a+low-molecular-weight+tracer.&rft.au=Croteau%2C+David%3BWalbridge%2C+Stuart%3BMorrison%2C+Paul+F%3BButman%2C+John+A%3BVortmeyer%2C+Alexander+O%3BJohnson%2C+Dennis%3BOldfield%2C+Edward+H%3BLonser%2C+Russell+R&rft.aulast=Croteau&rft.aufirst=David&rft.date=2005-01-01&rft.volume=102&rft.issue=1&rft.spage=90&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 - 2005-02-17 N1 - Date created - 2005-01-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer risk and exposure in early life to polycyclic aromatic hydrocarbons using total suspended particulates as a proxy measure. AN - 67376382; 15668476 AB - Polycyclic aromatic hydrocarbons (PAH) are ubiquitous in the environment. We hypothesized that early life exposure to PAHs may have particular importance in the etiology of breast cancer. We conducted a population-based, case-control study of ambient exposure to PAHs in early life in relation to the risk of breast cancer. Total suspended particulates (TSP), a measure of ambient air pollution, was used as a proxy for PAHs exposure. Cases (n = 1,166) were women with histologically confirmed, primary, incident breast cancer. Controls (n = 2,105) were frequency matched by age, race, and county of residence to cases. Annual average TSP concentrations (1959-1997) by location were obtained from the New York State Department of Environmental Conservation for Erie and Niagara Counties. Based on the monitor readings, prediction maps of TSP concentrations were generated with ArcGIS 8.0 (ESRI, Inc., Redlands, CA) using inverse distance squared weighted interpolation. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals. In postmenopausal women, exposure to high concentrations of TSP (>140 microg/m(3)) at birth was associated with an adjusted odds ratio of 2.42 (95% confidence interval, 0.97-6.09) compared with exposure to low concentrations (<84 microg/m(3)). However, in premenopausal women, where exposures were generally lower, the results were inconsistent with our hypothesis and in some instances were suggestive of a reduction in the risk of breast cancer. Our study suggests that exposure in early life to high levels of PAHs may increase the risk of postmenopausal breast cancer; however, other confounders related to geography cannot be ruled out. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Bonner, Matthew R AU - Han, Daikwon AU - Nie, Jing AU - Rogerson, Peter AU - Vena, John E AU - Muti, Paola AU - Trevisan, Maurizio AU - Edge, Stephen B AU - Freudenheim, Jo L AD - Department of Social and Preventive Medicine, School of Public Health and Professions, University at Buffalo, Buffalo, NY, USA. bonnerm@mail.nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 53 EP - 60 VL - 14 IS - 1 SN - 1055-9965, 1055-9965 KW - Air Pollutants KW - 0 KW - Polycyclic Aromatic Hydrocarbons KW - Index Medicus KW - Data Collection -- methods KW - Premenopause KW - Particle Size KW - Humans KW - Aged KW - New York -- epidemiology KW - Environmental Monitoring KW - Postmenopause KW - Logistic Models KW - Risk Factors KW - Adult KW - Confounding Factors (Epidemiology) KW - Case-Control Studies KW - Epidemiological Monitoring KW - Middle Aged KW - Female KW - Polycyclic Aromatic Hydrocarbons -- analysis KW - Polycyclic Aromatic Hydrocarbons -- adverse effects KW - Breast Neoplasms -- epidemiology KW - Breast Neoplasms -- chemically induced KW - Air Pollutants -- analysis KW - Environmental Exposure -- adverse effects KW - Air Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67376382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Breast+cancer+risk+and+exposure+in+early+life+to+polycyclic+aromatic+hydrocarbons+using+total+suspended+particulates+as+a+proxy+measure.&rft.au=Bonner%2C+Matthew+R%3BHan%2C+Daikwon%3BNie%2C+Jing%3BRogerson%2C+Peter%3BVena%2C+John+E%3BMuti%2C+Paola%3BTrevisan%2C+Maurizio%3BEdge%2C+Stephen+B%3BFreudenheim%2C+Jo+L&rft.aulast=Bonner&rft.aufirst=Matthew&rft.date=2005-01-01&rft.volume=14&rft.issue=1&rft.spage=53&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 - 2005-04-20 N1 - Date created - 2005-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microsomal epoxide hydrolase polymorphisms and risk for advanced colorectal adenoma. AN - 67373858; 15668489 AB - Cigarette smoking is a risk factor for colorectal adenoma, a precursor of colorectal cancer. Microsomal epoxide hydrolase (EPHX1) metabolizes polycyclic aromatic hydrocarbons, carcinogens found in cigarette smoke. Nonsynonymous variants of EPHX1 at Tyr(113)His (exon 3) and His(139)Arg (exon 4) are associated, respectively, with low ((113)His) and high ((139)Arg) predicted activity. Among participants randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we evaluated risks for advanced adenoma in relation to cigarette use and these two EPHX1 variants. We compared 772 cases with advanced adenoma (adenoma >/=1 cm or containing high-grade dysplasia or villous, including tubulovillous, elements) of the distal colon (left-sided, descending colon and sigmoid or rectum) to 777 gender- and age-matched controls who were screen-negative for left-sided adenoma. Compared to those with homozygous genotypes predicting low EPHX1 activity, advanced adenoma risks tended to be elevated for carriers of (113)TyrTyr [odds ratios (OR), 1.5; 95% confidence intervals (CI), 1.0-2.2] and (139)ArgArg (OR, 1.4; 95% CI, 0.8-2.5) and for subjects who carried a greater number of the alleles ((113)Tyr or (139)Arg) associated with high predicted enzymatic activity (P(trend) = 0.03). The increased risk associated with the increasing number of putative high-activity alleles was most apparent among current and recent (quit <10 years) cigarette smokers (P(trend) = 0.02). In conclusion, EPHX1 variants at codon 113 and 139 associated with high predicted enzymatic activity appear to increase risk for colorectal adenoma, particularly among recent and current smokers. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Huang, Wen-Yi AU - Chatterjee, Nilanjan AU - Chanock, Stephen AU - Dean, Michael AU - Yeager, Meredith AU - Schoen, Robert E AU - Hou, Li-Fang AU - Berndt, Sonja I AU - Yadavalli, Sunita AU - Johnson, Christine C AU - Hayes, Richard B AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, EPS 8113, MSC 7240, Bethesda, MD 20892, USA. huangw@mail.nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 152 EP - 157 VL - 14 IS - 1 SN - 1055-9965, 1055-9965 KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - Index Medicus KW - Genotype KW - Logistic Models KW - Exons KW - Risk Factors KW - Humans KW - Chi-Square Distribution KW - Surveys and Questionnaires KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Epoxide Hydrolases -- genetics KW - Epoxide Hydrolases -- metabolism KW - Polymorphism, Genetic KW - Smoking -- adverse effects 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/67373858?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Microsomal+epoxide+hydrolase+polymorphisms+and+risk+for+advanced+colorectal+adenoma.&rft.au=Huang%2C+Wen-Yi%3BChatterjee%2C+Nilanjan%3BChanock%2C+Stephen%3BDean%2C+Michael%3BYeager%2C+Meredith%3BSchoen%2C+Robert+E%3BHou%2C+Li-Fang%3BBerndt%2C+Sonja+I%3BYadavalli%2C+Sunita%3BJohnson%2C+Christine+C%3BHayes%2C+Richard+B&rft.aulast=Huang&rft.aufirst=Wen-Yi&rft.date=2005-01-01&rft.volume=14&rft.issue=1&rft.spage=152&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 - 2005-04-20 N1 - Date created - 2005-01-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression-based discovery of variation in the human glutathione S-transferase M3 promoter and functional analysis in a glioma cell line using allele-specific chromatin immunoprecipitation. AN - 67370850; 15665284 AB - Discovery and functional evaluation of biologically significant regulatory single nucleotide polymorphisms (SNP) in carcinogen metabolism genes is a difficult challenge because the phenotypic consequences may be both transient and subtle. We have used a gene expression screening approach to identify a functional regulatory SNP in glutathione S-transferase M3 (GSTM3). Anttila et al. proposed that variation in GSTM3 expression was affected by exposure to cigarette smoke and inheritance of the GSTM1-null genotype. To investigate the mechanism of GSTM3 expression was affected by exposure to cigarette smoke and inheritance of the GSTM1-null genotype. To investigate the mechanism of GSTM3 expression variation, we measured GSTM3 expression in lymphoblast cells from a human Centre d'Etude du Polymorphisme Humain family and observed a low expression phenotype. Promoter sequencing revealed two novel GSTM3 promoter SNPs: A/C and A/G SNPs, 63 and 783 bp upstream of the codon 1 start site, respectively. In this pedigree, the two children homozygous for the -63C/C genotype had 8-fold lower GSTM3 expression relative to the two children with the -63A/A genotype, with no association between A-783G SNP and GSTM3 expression. Further evaluation using genotyped glioma cell lines and with luciferase reporter constructs showed that the -63C allele was associated with lower GSTM3 expression (P < 0.0001 and P < 0.003). RNA pol II chromatin immunoprecipitation was combined with quantitative probed-based allelic discrimination genotyping to provide direct evidence of a 9-fold reduced RNA pol II binding capacity for the -63C allele. These results show that the GSTM3 -63C allele strongly affects gene expression in human cell lines and suggests that individuals who carry the low expression allele may be deficient in glutathione transferase catalyzed biological functions. JF - Cancer research AU - Liu, Xuemei AU - Campbell, Michelle R AU - Pittman, Gary S AU - Faulkner, Eric C AU - Watson, Mary A AU - Bell, Douglas A AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - 99 EP - 104 VL - 65 IS - 1 SN - 0008-5472, 0008-5472 KW - Chromatin KW - 0 KW - DNA Primers KW - DNA, Neoplasm KW - GSTM3 protein, human KW - EC 2.5.1.18 KW - Glutathione Transferase KW - Index Medicus KW - Pedigree KW - Humans KW - Cell Line, Tumor KW - Chromatin -- genetics KW - Phenotype KW - Gene Expression Regulation, Neoplastic KW - Genotype KW - Polymerase Chain Reaction KW - Base Sequence KW - Gene Expression Regulation, Enzymologic KW - DNA, Neoplasm -- genetics KW - Glioma KW - Female KW - Male KW - Promoter Regions, Genetic -- genetics KW - Glutathione Transferase -- genetics KW - Genetic Variation -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67370850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Expression-based+discovery+of+variation+in+the+human+glutathione+S-transferase+M3+promoter+and+functional+analysis+in+a+glioma+cell+line+using+allele-specific+chromatin+immunoprecipitation.&rft.au=Liu%2C+Xuemei%3BCampbell%2C+Michelle+R%3BPittman%2C+Gary+S%3BFaulkner%2C+Eric+C%3BWatson%2C+Mary+A%3BBell%2C+Douglas+A&rft.aulast=Liu&rft.aufirst=Xuemei&rft.date=2005-01-01&rft.volume=65&rft.issue=1&rft.spage=99&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 - 2005-03-02 N1 - Date created - 2005-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk. AN - 67369749; 15654286 AB - Alcoholism is a complex, genetically influenced disorder the cause of which may be better understood through the study of genetically influenced phenotypes that mediate the risk. One such intermediate phenotype is the low level of response (LR) to alcohol. This project used a case-control approach to search for genes that may contribute to LR. Data were available from alcohol challenges at approximately age 20 and regarding the development of alcohol use disorders over the subsequent 20 years for 85 men, including 40 reported in a previous genetic analysis. LR was evaluated using oral consumption of 0.75 ml/kg of alcohol, after which changes in subjective feelings of intoxication and body sway were measured. Alcohol abuse and dependence were diagnosed by DSM-III-R criteria through structured interviews administered to both the participant and an informant (usually the spouse) 10, 15, and 20 years after initial testing. Four polymorphisms were evaluated, including the serotonin transporter HTTLPR promoter ins/del, GABAAalpha6 Pro385Ser, NPY Leu7Pro, and catalase 262C>T. Two of these, HTTLPR and GABAAalpha6 Pro385Ser, had been previously associated with LR and alcoholism in a preliminary study. The HTTLPR L allele was significantly related to both the LR and alcoholism in an allele-dosage (stepwise) manner. Furthermore, the association remained when L alleles were subdivided into recently reported functional subtypes: the lowest LR was associated with genotypes correlated with the highest serotonin transporter expression. The GABAAalpha6 Ser385 allele showed a nonsignificant trend for association to a low LR, as had been previously observed, although the Ser385 allele is uncommon, and only 18 heterozygotes were in the current group. However, the six men with both LL and Pro385/Ser385 genotypes had the lowest LR, and each had developed alcoholism during follow-up. Neither NPY nor catalase was associated with either LR or alcoholic outcomes, although the sample did not have sufficient power for definitive conclusions. This report strengthens the support for a relationship between the HTTLPR L and GABAAalpha6 Ser385 alleles to low alcohol LR and to alcoholism in a prospectively studied cohort evaluated for LR in young adulthood and before the onset of alcohol dependence. JF - Alcoholism, clinical and experimental research AU - Hu, Xianzhang AU - Oroszi, Gabor AU - Chun, Jeffrey AU - Smith, Tom L AU - Goldman, David AU - Schuckit, Marc A AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA. Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 8 EP - 16 VL - 29 IS - 1 SN - 0145-6008, 0145-6008 KW - Membrane Glycoproteins KW - 0 KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Receptors, GABA-A KW - SLC6A4 protein, human KW - Serotonin Plasma Membrane Transport Proteins KW - Index Medicus KW - Receptors, GABA-A -- genetics KW - Prospective Studies KW - Risk Factors KW - Humans KW - Adult KW - Follow-Up Studies KW - Nerve Tissue Proteins -- genetics KW - Membrane Transport Proteins -- genetics KW - Male KW - Membrane Glycoproteins -- genetics KW - Alleles KW - Alcohol Drinking -- genetics KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67369749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=An+expanded+evaluation+of+the+relationship+of+four+alleles+to+the+level+of+response+to+alcohol+and+the+alcoholism+risk.&rft.au=Hu%2C+Xianzhang%3BOroszi%2C+Gabor%3BChun%2C+Jeffrey%3BSmith%2C+Tom+L%3BGoldman%2C+David%3BSchuckit%2C+Marc+A&rft.aulast=Hu&rft.aufirst=Xianzhang&rft.date=2005-01-01&rft.volume=29&rft.issue=1&rft.spage=8&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 - 2005-05-25 N1 - Date created - 2005-01-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional roles of carboxylate residues comprising the DNA polymerase active site triad of Ty3 reverse transcriptase. AN - 67368017; 15647500 AB - Aspartic acid residues comprising the -D-(aa) n -Y-L-D-D- DNA polymerase active site triad of reverse transcriptase from the Saccharomyces cerevisiae long terminal repeat-retrotransposon Ty3 (Asp151, Asp213 and Asp214) were evaluated via site-directed mutagenesis. An Asp151-->Glu substitution showed a dramatic decrease in catalytic efficiency and a severe translocation defect following initiation of DNA synthesis. In contrast, enzymes harboring the equivalent alteration at Asp213 and Asp214 retained DNA polymerase activity. Asp151-->Asn and Asp213-->Asn substitutions eliminated both polymerase activities. However, while Asp214 of the triad could be replaced by either Asn or Glu, introducing Gln seriously affected processivity. Mutants of the carboxylate triad at positions 151 and 213 also failed to catalyze pyrophosphorolysis. Finally, alterations to the DNA polymerase active site affected RNase H activity, suggesting a close spatial relationship between these N- and C-terminal catalytic centers. Taken together, our data reveal a critical role for Asp151 and Asp213 in catalysis. In contrast, the second carboxylate of the Y-L-D-D motif (Asp214) is not essential for catalysis, and possibly fulfills a structural role. Although Asp214 was most insensitive to substitution with respect to activity of the recombinant enzyme, all alterations at this position were lethal for Ty3 transposition. JF - Nucleic acids research AU - Bibillo, Arkadiusz AU - Lener, Daniela AU - Klarmann, George J AU - Le Grice, Stuart F J AD - Resistance Mechanisms Laboratory, RT Biochemistry Section, HIV Drug Resistance Program, National Cancer Institute at Frederick Frederick, MD 21702, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 171 EP - 181 VL - 33 IS - 1 KW - Phosphoric Acids KW - 0 KW - Retroelements KW - Saccharomyces cerevisiae Proteins KW - Aspartic Acid KW - 30KYC7MIAI KW - Manganese KW - 42Z2K6ZL8P KW - DNA KW - 9007-49-2 KW - RNA-Directed DNA Polymerase KW - EC 2.7.7.49 KW - reverse transcriptase Ty3, S cerevisiae KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Ribonuclease H KW - EC 3.1.26.4 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Kinetics KW - DNA -- metabolism KW - Phosphoric Acids -- metabolism KW - Manganese -- chemistry KW - Ribonuclease H -- metabolism KW - Amino Acid Substitution KW - DNA-Directed DNA Polymerase -- metabolism KW - Binding Sites KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Saccharomyces cerevisiae Proteins -- genetics KW - RNA-Directed DNA Polymerase -- chemistry KW - RNA-Directed DNA Polymerase -- metabolism KW - Saccharomyces cerevisiae Proteins -- chemistry KW - RNA-Directed DNA Polymerase -- genetics KW - Aspartic Acid -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67368017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Functional+roles+of+carboxylate+residues+comprising+the+DNA+polymerase+active+site+triad+of+Ty3+reverse+transcriptase.&rft.au=Bibillo%2C+Arkadiusz%3BLener%2C+Daniela%3BKlarmann%2C+George+J%3BLe+Grice%2C+Stuart+F+J&rft.aulast=Bibillo&rft.aufirst=Arkadiusz&rft.date=2005-01-01&rft.volume=33&rft.issue=1&rft.spage=171&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 - 2005-02-10 N1 - Date created - 2005-01-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1994 Oct 28;243(3):472-83 [7525967] J Biol Chem. 2004 Nov 12;279(46):47840-8 [15333632] Science. 1995 Jan 6;267(5194):96-9 [7528942] Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1222-6 [7532306] Biochemistry. 1995 Apr 25;34(16):5343-56 [7537089] Biochemistry. 1995 May 30;34(21):7207-16 [7539293] Biochemistry. 1995 Aug 8;34(31):9936-43 [7543283] Structure. 1995 Sep 15;3(9):879-92 [8535782] Methods Enzymol. 1995;262:130-44 [8594344] Biochemistry. 1996 Jul 2;35(26):8553-62 [8679616] Biochemistry. 1996 Sep 10;35(36):11536-46 [8794733] Methods Enzymol. 1996;275:398-424 [9026652] J Biol Chem. 1997 Apr 25;272(17):11157-64 [9111014] Cell. 1997 Jun 27;89(7):1087-99 [9215631] Nature. 1998 Jan 15;391(6664):251-8 [9440688] EMBO J. 1998 Aug 17;17(16):4873-80 [9707446] J Mol Biol. 1998 Oct 30;283(3):633-42 [9784372] J Biol Chem. 1998 Nov 13;273(46):30435-42 [9804810] Biochemistry. 1999 Mar 2;38(9):2617-27 [10052931] J Biol Chem. 1999 Jun 18;274(25):17395-8 [10364165] J Virol. 2000 Apr;74(7):3245-52 [10708441] Biochemistry. 2000 Mar 21;39(11):2912-20 [10715111] J Biol Inorg Chem. 2000 Feb;5(1):67-74 [10766438] Eur J Biochem. 2000 May;267(9):2658-65 [10785387] J Biol Chem. 2000 May 5;275(18):13879-87 [10788512] Chem Biol. 2000 May;7(5):355-64 [10801473] Biochem J. 2000 Jun 1;348 Pt 2:337-42 [10816427] Eur J Biochem. 2000 Aug;267(15):4740-4 [10903507] EMBO J. 2001 Mar 15;20(6):1449-61 [11250910] Virology. 2001 Mar 30;282(1):206-13 [11259203] Methods Mol Biol. 2001;160:335-54 [11265294] J Virol. 2001 Jul;75(14):6337-47 [11413300] Genome Res. 2001 Jul;11(7):1187-97 [11435400] J Biol Chem. 2001 Dec 14;276(50):47695-701 [11595735] J Biol Chem. 2002 Jul 19;277(29):26486-95 [11994277] EMBO J. 2002 Dec 2;21(23):6614-24 [12456667] Biochemistry. 2002 Dec 17;41(50):14831-42 [12475231] J Biol Chem. 2003 Jul 18;278(29):26526-32 [12730227] Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 [3881765] Nature. 1987 Jun 25-Jul 1;327(6124):716-7 [2439916] Proc Natl Acad Sci U S A. 1988 Feb;85(4):1218-22 [2448794] J Biol Chem. 1988 Oct 25;263(30):15657-65 [2459125] J Biol Chem. 1989 Mar 15;264(8):4669-78 [2466838] Mol Cell Biol. 1988 Dec;8(12):5245-56 [2854194] EMBO J. 1989 Dec 1;8(12):3867-74 [2555175] J Virol. 1990 Jun;64(6):2599-607 [2159534] Protein Eng. 1990 May;3(6):461-7 [2196557] EMBO J. 1991 Jan;10(1):25-33 [1989886] J Biol Chem. 1991 Jul 25;266(21):14128-34 [1713216] EMBO J. 1991 Dec;10(12):3905-11 [1718745] Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9652-6 [1384059] J Virol. 1992 Dec;66(12):7533-7 [1279205] J Biol Chem. 1992 Dec 25;267(36):25988-97 [1281479] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5909-13 [7687057] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6320-4 [7687065] J Biol Chem. 1994 Oct 21;269(42):26472-8 [7523408] RNA. 1999 Jul;5(7):929-38 [10411136] Mol Cell Biol. 1994 Dec;14(12):8229-40 [7969160] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Can animal models help us select specific compounds for cancer prevention trials? AN - 67365803; 15648184 AB - Animal models provide unparalleled mechanistic insights into cancer development and potential opportunity for cancer prevention. Nevertheless, species differ markedly with regard to dietary exposures, cancer development, drug effects, and toxicity thresholds; therefore, testing in a single animal system may not predict human responses. Although replication of human cancer in animal models remains inexact, more than two decades of research have clearly yielded significant gains, as is evident in agents tested--and in certain cases, approved--for the prevention of epithelial cancers. Research efficiencies achievable through preliminary testing in genetically engineered and carcinogen-induced animal models enable us to probe genetic and signaling pathways that drive normal and neoplastic processes, and thereby figure prominently in decision trees for agent development. JF - Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer AU - Hawk, Ernest T AU - Umar, Asad AU - Lubet, Ronald A AU - Kopelovich, Levy AU - Viner, Jaye L AD - GI and Other Cancers Research Group, National Cancer Institute, Suite 2141, 6130 Executive Boulevard, Bethesda, MD 20892-7317, USA. hawke@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 71 EP - 87 VL - 166 SN - 0080-0015, 0080-0015 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Clinical Trials as Topic KW - Models, Animal KW - Neoplasms, Experimental -- prevention & control KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67365803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.atitle=Can+animal+models+help+us+select+specific+compounds+for+cancer+prevention+trials%3F&rft.au=Hawk%2C+Ernest+T%3BUmar%2C+Asad%3BLubet%2C+Ronald+A%3BKopelovich%2C+Levy%3BViner%2C+Jaye+L&rft.aulast=Hawk&rft.aufirst=Ernest&rft.date=2005-01-01&rft.volume=166&rft.issue=&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Recent+results+in+cancer+research.+Fortschritte+der+Krebsforschung.+Progres+dans+les+recherches+sur+le+cancer&rft.issn=00800015&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-10 N1 - Date created - 2005-01-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Working with transmissible spongiform encephalopathy agents. AN - 67360031; 15644563 AB - The family of illnesses called transmissible spongiform encephalopathies (TSEs), or "prion" diseases, is composed of a small number of human and animal neurodegenerative diseases caused by unique pathogenic agents that are still not fully defined. They are best considered as "protein-misfolding diseases" (together with Alzheimer's disease, Parkinson's disease, and a few other rare examples) resulting from the conversion of a normal body protein into a misfolded amyloid multimer. The pathogenic agents display a unique resistance to conventional disinfection methods and an extraordinary environmental durability, which has led the US Department of Agriculture to designate the causative agent of bovine spongiform encephalopathy as a bioterrorism security threat. In this review, precautions and regulations concerning the handling of TSE agents are discussed in relation to personnel and environmental biosafety. JF - ILAR journal AU - Brown, Paul AU - Abee, Christian R AD - National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2005 PY - 2005 DA - 2005 SP - 44 EP - 52 VL - 46 IS - 1 SN - 1084-2020, 1084-2020 KW - Hazardous Substances KW - 0 KW - Prions KW - Index Medicus KW - Animals KW - Humans KW - Social Control, Formal KW - Prion Diseases -- etiology KW - Prion Diseases -- prevention & control KW - Containment of Biohazards -- methods KW - Prion Diseases -- transmission UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67360031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ILAR+journal&rft.atitle=Working+with+transmissible+spongiform+encephalopathy+agents.&rft.au=Brown%2C+Paul%3BAbee%2C+Christian+R&rft.aulast=Brown&rft.aufirst=Paul&rft.date=2005-01-01&rft.volume=46&rft.issue=1&rft.spage=44&rft.isbn=&rft.btitle=&rft.title=ILAR+journal&rft.issn=10842020&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-15 N1 - Date created - 2005-01-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin-7 deficiency in rheumatoid arthritis. AN - 67359209; 15642153 AB - Interleukin-7 (IL-7) is a stromal factor that is crucial for the development of T lymphocytes in humans and mice, and also B lymphocytes in mice. IL-7 can act as a T cell growth factor as well as a critical anti-apoptotic survival factor. The essential non-redundant role of this cytokine for T cell development in vivo is indicated by the phenotype of murine knockout models as well as by humans with a T-B+NK+ form of severe combined immunodeficiency (SCID) resulting from mutations in IL-7 receptor alpha chain. IL-7 deficiency has now been found in patients with rheumatoid arthritis, a finding that relates not only to the T-lymphocyte status in this disease but also to the ability of patients with rheumatoid arthritis to recover from therapy-induced lymphopenia. JF - Arthritis research & therapy AU - Leonard, Warren J AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. wjl@helix.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 42 EP - 43 VL - 7 IS - 1 KW - Antirheumatic Agents KW - 0 KW - Interleukin-7 KW - Receptors, Interleukin-7 KW - Tumor Necrosis Factor-alpha KW - interleukin-7 receptor, alpha chain KW - Index Medicus KW - Receptors, Interleukin-7 -- deficiency KW - Severe Combined Immunodeficiency -- metabolism KW - Humans KW - Receptors, Interleukin-7 -- physiology KW - Bone Marrow -- metabolism KW - Tumor Necrosis Factor-alpha -- physiology KW - Severe Combined Immunodeficiency -- genetics KW - Gene Rearrangement, T-Lymphocyte KW - Tumor Necrosis Factor-alpha -- antagonists & inhibitors KW - Stromal Cells -- metabolism KW - Antirheumatic Agents -- therapeutic use KW - Bone Marrow Transplantation KW - Female KW - Male KW - Arthritis, Rheumatoid -- drug therapy KW - Lymphopenia -- chemically induced KW - Arthritis, Rheumatoid -- blood KW - Interleukin-7 -- deficiency KW - Lymphocyte Depletion KW - Interleukin-7 -- blood KW - Interleukin-7 -- biosynthesis KW - Autoimmune Diseases -- drug therapy KW - CD4-Positive T-Lymphocytes -- pathology KW - Autoimmune Diseases -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67359209?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+research+%26+therapy&rft.atitle=Interleukin-7+deficiency+in+rheumatoid+arthritis.&rft.au=Leonard%2C+Warren+J&rft.aulast=Leonard&rft.aufirst=Warren&rft.date=2005-01-01&rft.volume=7&rft.issue=1&rft.spage=42&rft.isbn=&rft.btitle=&rft.title=Arthritis+research+%26+therapy&rft.issn=1478-6362&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-03-24 N1 - Date created - 2005-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 2000 Sep 4;192(5):659-70 [10974032] Immunity. 2004 Aug;21(2):289-302 [15308108] Annu Rev Immunol. 2001;19:163-96 [11244034] Nat Immunol. 2000 Jul;1(1):59-64 [10881176] Nat Rev Immunol. 2001 Dec;1(3):200-8 [11905829] Blood. 2002 Jun 1;99(11):3892-904 [12010786] Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13759-64 [12354940] Science. 2002 Nov 22;298(5598):1630-4 [12446913] Nat Rev Immunol. 2003 Apr;3(4):269-79 [12669018] Nat Immunol. 2004 Apr;5(4):426-34 [14991051] Arthritis Rheum. 2004 Jun;50(6):1761-9 [15188351] Arthritis Rheum. 2004 Jul;50(7):2041-3 [15248200] J Exp Med. 2004 Jul 19;200(2):159-68 [15263024] Nat Immunol. 2004 Oct;5(10):1036-44 [15361867] Annu Rev Immunol. 1996;14:397-440 [8717520] Nat Genet. 1998 Dec;20(4):394-7 [9843216] Arthritis Res Ther. 2005;7(1):R80-92 [15642146] Comment On: Arthritis Res Ther. 2005;7(1):R80-92 [15642146] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiation and breast cancer: a review of current evidence. AN - 67358854; 15642178 AB - This paper summarizes current knowledge on ionizing radiation-associated breast cancer in the context of established breast cancer risk factors, the radiation dose-response relationship, and modifiers of dose response, taking into account epidemiological studies and animal experiments. Available epidemiological data support a linear dose-response relationship down to doses as low as about 100 mSv. However, the magnitude of risk per unit dose depends strongly on when radiation exposure occurs: exposure before the age of 20 years carries the greatest risk. Other characteristics that may influence the magnitude of dose-specific risk include attained age (that is, age at observation for risk), age at first full-term birth, parity, and possibly a history of benign breast disease, exposure to radiation while pregnant, and genetic factors. JF - Breast cancer research : BCR AU - Ronckers, Cécile M AU - Erdmann, Christine A AU - Land, Charles E AD - National Cancer Institute, Division of Cancer Epidemiology and Genetics, NIH, HHS, Bethesda, Maryland, USA. ronckerc@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 21 EP - 32 VL - 7 IS - 1 KW - Index Medicus KW - Age Factors KW - Epidemiologic Studies KW - Risk Factors KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Genetic Predisposition to Disease KW - Dose-Response Relationship, Radiation KW - Adolescent KW - Female KW - Pregnancy KW - Neoplasms, Radiation-Induced -- physiopathology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- epidemiology KW - Radiation, Ionizing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67358854?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+%3A+BCR&rft.atitle=Radiation+and+breast+cancer%3A+a+review+of+current+evidence.&rft.au=Ronckers%2C+C%C3%A9cile+M%3BErdmann%2C+Christine+A%3BLand%2C+Charles+E&rft.aulast=Ronckers&rft.aufirst=C%C3%A9cile&rft.date=2005-01-01&rft.volume=7&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+%3A+BCR&rft.issn=1465-542X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-01-31 N1 - Date created - 2005-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Natl Cancer Inst. 1980 Sep;65(3):559-69 [6931935] Prev Med. 1980 Nov;9(6):815-22 [7454704] Cancer Res. 1982 Jan;42(1):50-3 [7053866] Cancer Res. 1982 Aug;42(8):3232-9 [7046921] Nature. 1983 Jun 30;303(5920):767-70 [6866078] J Natl Cancer 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15;526(1-2):93-125 [12714187] Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5057-62 [12679524] Cancer. 2003 Jun 15;97(12):3080-9 [12784345] J Natl Cancer Inst. 2003 Jul 2;95(13):971-80 [12837833] Health Phys. 2003 Jul;85(1):43-6 [12852470] JAMA. 2003 Jul 23;290(4):465-75 [12876089] Mol Cell Biol. 2003 Aug;23(16):5706-15 [12897142] Expert Rev Anticancer Ther. 2003 Aug;3(4):546-62 [12934666] Mayo Clin Proc. 2003 Jun;78(6):708-15 [12934780] Br J Cancer. 2003 Oct 20;89(8):1513-6 [14562025] Genes Chromosomes Cancer. 1999 Aug;25(4):393-5 [10398434] Ann ICRP. 1998;28(1-2):1-157 [10406427] J Clin Oncol. 2003 Dec 1;21(23):4386-94 [14645429] Radiat Res. 2003 Dec;160(6):707-17 [14640793] CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29 [14974761] J Natl Cancer Inst. 2004 Mar 3;96(5):357-63 [14996857] Am J Epidemiol. 2004 Apr 1;159(7):671-82 [15033645] Int J Radiat Oncol Biol Phys. 2004 Apr 1;58(5):1474-9 [15050326] Br J Cancer. 2004 Apr 5;90(7):1297-301 [15054444] J Natl Cancer Inst. 2004 Apr 7;96(7):539-46 [15069116] Mol Carcinog. 1999 Nov;26(3):143-9 [10559788] J Clin Oncol. 2000 Feb;18(3):487-97 [10653864] J Clin Oncol. 2000 Feb;18(3):498-509 [10653865] Am J Hum Genet. 2000 Feb;66(2):494-500 [10677309] Arch Dis Child. 2000 May;82(5):400-6 [10799436] J Natl Cancer Inst. 2000 May 17;92(10):795-802 [10814674] J Clin Oncol. 2000 Jun;18(12):2435-43 [10856104] N Engl J Med. 2000 Jul 13;343(2):78-85 [10891514] J Natl Cancer Inst. 2000 Jul 19;92(14):1114-5 [10904078] Spine (Phila Pa 1976). 2000 Aug 15;25(16):2052-63 [10954636] Int J Radiat Oncol Biol Phys. 2000 Nov 1;48(4):959-65 [11072151] J Mammary Gland Biol Neoplasia. 2000 Apr;5(2):119-37 [11149569] Int J Radiat Oncol Biol Phys. 2001 Feb 1;49(2):539-46 [11173152] J Natl Cancer Inst. 2001 Jan 17;93(2):121-7 [11208881] J Natl Cancer Inst. 2001 Apr 18;93(8):618-29 [11309438] Ophthalmology. 2001 Jun;108(6):1109-14 [11382638] Oncogene. 2001 Jul 19;20(32):4409-11 [11466622] Int J Cancer. 2001 Aug 20;96(4):238-42 [11474498] Br J Cancer. 2001 Aug 3;85(3):362-6 [11487266] Lancet. 2001 Oct 27;358(9291):1389-99 [11705483] Lancet Oncol. 2001 Sep;2(9):533-43 [11905707] J Natl Cancer Inst. 2002 Apr 17;94(8):606-16 [11959894] Int J Radiat Biol. 2002 Apr;78(4):285-95 [12020440] Hum Mol Genet. 2002 Jun 1;11(12):1399-407 [12023982] Cancer Causes Control. 2002 May;13(4):295-8 [12074498] Cancer Causes Control. 2002 May;13(4):299-305 [12074499] Radiat Res. 2002 Aug;158(2):220-35 [12105993] J Clin Oncol. 2002 Aug 15;20(16):3484-94 [12177110] Am J Epidemiol. 2003 Dec 1;158(11):1108-13 [14630607] Breast Cancer Res. 2004;6(3):R199-214 [15084244] BMC Cancer. 2004 Mar 12;4:9 [15113441] Ann Intern Med. 2004 Oct 19;141(8):590-7 [15492338] Bull World Health Organ. 1970;43(2):209-21 [5312521] J Natl Cancer Inst. 1975 Aug;55(2):485-7 [1159830] J Natl Cancer Inst. 1977 Sep;59(3):799-811 [894745] J Natl Cancer Inst. 1979 Jun;62(6):1347-59 [286106] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TP-3 immunotoxins improve antitumor activity in mice with osteosarcoma. AN - 67356618; 15662316 AB - We measured the antitumor activity of two types of TP-3 immunotoxins that target an antigen expressed in tumors associated with osteosarcoma. Development of novel agents for treatment of patients with osteosarcoma is important. We previously described a monovalent-disulfide-stabilized recombinant immunotoxin made from the TP-3 antibody. This agent is called TP-3(dsFv)-PE38 and is cytotoxic to human osteosarcoma cells in vitro. To improve antigen binding, we designed and produced a bivalent immunotoxin, TP-3(dsFv)2-PE38. We evaluated the activity of both molecules in vitro and in vivo using tumor-bearing mice. Compared with the monovalent TP-3 immunotoxin, the bivalent TP-3 immunotoxin showed an approximately sevenfold increase in cytotoxic activity against three osteosarcoma cell lines which react with the TP-3 monoclonal antibody. The apparent affinity of the bivalent TP-3 immunotoxin was 12-fold greater than that of the monovalent TP-3 immunotoxin. The antitumor activities of both TP-3 immunotoxins were measured using severe combined immunodeficient mice bearing osteosarcoma cell line OHS-M1 tumors. The dose at which the bivalent TP-3 immunotoxin produces complete regressions of tumors is (1/2) that of the monovalent TP-3 immunotoxin. Increasing the avidity of TP-3(dsFv)-PE38 significantly improves its cytotoxic activity in vitro and results in a twofold increase in antitumor activity in vivo. Because TP-3-based immunotoxins have good antitumor activity in mice, these molecules merit additional development for possible treatment of osteosarcoma in humans. JF - Clinical orthopaedics and related research AU - Onda, Masanori AU - Bruland, Øyvind S AU - Pastan, Ira AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA. ondam@pop.nci.nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 142 EP - 148 IS - 430 SN - 0009-921X, 0009-921X KW - Immunotoxins KW - 0 KW - Peptide Fragments KW - Thymopoietins KW - splenotritin KW - 105803-00-7 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Xenograft Model Antitumor Assays -- methods KW - Dose-Response Relationship, Drug KW - Humans KW - Treatment Outcome KW - Disease Models, Animal KW - Mice KW - Mice, SCID KW - Osteosarcoma -- drug therapy KW - Thymopoietins -- immunology KW - Peptide Fragments -- therapeutic use KW - Bone Neoplasms -- immunology KW - Thymopoietins -- therapeutic use KW - Bone Neoplasms -- drug therapy KW - Immunotoxins -- therapeutic use KW - Peptide Fragments -- immunology KW - Osteosarcoma -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67356618?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+orthopaedics+and+related+research&rft.atitle=TP-3+immunotoxins+improve+antitumor+activity+in+mice+with+osteosarcoma.&rft.au=Onda%2C+Masanori%3BBruland%2C+%C3%98yvind+S%3BPastan%2C+Ira&rft.aulast=Onda&rft.aufirst=Masanori&rft.date=2005-01-01&rft.volume=&rft.issue=430&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Clinical+orthopaedics+and+related+research&rft.issn=0009921X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-15 N1 - Date created - 2005-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene-environment interactions in asthma and other respiratory diseases. AN - 67355191; 15660518 AB - It is generally agreed that many lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) have polygenic inheritance, and that the association of a specific genotype or genotypes with the disease is likely to vary between populations. Furthermore, it is recognized that the etiology of many lung diseases involves a complex interplay between genetic background and exposure to multiple environmental stimuli, and understanding the mechanisms through which genes and environment interact represents a major challenge for pulmonary researchers. We discuss experimental approaches and challenges that must be overcome to identify disease genes for asthma, COPD and chronic bronchitis, and occupational lung diseases. In particular, common polymorphisms in CD14, glutathione S-transferase, and tumor necrosis factor alpha have been found to be important in gene-environment interaction and asthma pathogenesis. An understanding of gene-environment interactions in complex lung diseases is essential to the development of new strategies for lung disease prevention and treatment. JF - Annual review of medicine AU - Kleeberger, Steven R AU - Peden, David AD - Laboratory of Respiratory Biology, Environmental Genetics Group, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina 27709, USA. kleeber1@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 383 EP - 400 VL - 56 SN - 0066-4219, 0066-4219 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Risk Factors KW - Humans KW - Statistics as Topic KW - Pulmonary Disease, Chronic Obstructive -- genetics KW - Pneumoconiosis -- genetics KW - Genetic Predisposition to Disease -- genetics KW - Asthma -- genetics KW - Bronchitis, Chronic -- genetics KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67355191?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+review+of+medicine&rft.atitle=Gene-environment+interactions+in+asthma+and+other+respiratory+diseases.&rft.au=Kleeberger%2C+Steven+R%3BPeden%2C+David&rft.aulast=Kleeberger&rft.aufirst=Steven&rft.date=2005-01-01&rft.volume=56&rft.issue=&rft.spage=383&rft.isbn=&rft.btitle=&rft.title=Annual+review+of+medicine&rft.issn=00664219&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-19 N1 - Date created - 2005-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bone mineral density in lymphangioleiomyomatosis. AN - 67350337; 15466255 AB - Estrogen deficiency and pulmonary diseases are associated with bone mineral density (BMD) loss. Lymphangioleiomyomatosis (LAM), a disorder affecting women that is characterized by cystic lung lesions, is frequently treated with antiestrogen therapy, i.e., progesterone and/or oophorectomy. Therefore, we evaluated BMD yearly in 211 LAM patients to determine the prevalence of BMD abnormalities, whether antiestrogen therapy decreased BMD, and if treatment with bisphosphonates prevented bone loss. Abnormal BMD was found in 70% of the patients and correlated with severity of lung disease and age. Greater severity of lung disease, menopause, and oophorectomy were associated with greater decline in BMD. After adjusting for differences in initial lung function and BMD, we found similar rates of BMD decline in progesterone-treated (n = 122) and untreated patients (n = 89). After similar adjustments, we found that bisphosphonate-treated patients (n = 98) had lower rates of decline in lumbar spine BMD (-0.004 +/- 0.003 vs. -0.015 +/- 0.003 gm/cm(2), p = 0.036) and T-scores (-0.050 +/- 0.041 vs. -0.191 +/- 0.041, p < 0.001) than untreated patients (n = 113). We conclude that abnormal BMD was frequent in LAM. Progesterone therapy was not associated with changes in BMD; bisphosphonate therapy was associated with lower rates of bone loss. We recommend systematic evaluation of BMD and early treatment with bisphosphonates for patients with LAM. JF - American journal of respiratory and critical care medicine AU - Taveira-Dasilva, Angelo M AU - Stylianou, Mario P AU - Hedin, Carolyn J AU - Hathaway, Olanda AU - Moss, Joel 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. dasilvaa@nhlbi.nih.gov Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - 61 EP - 67 VL - 171 IS - 1 SN - 1073-449X, 1073-449X KW - Diphosphonates KW - 0 KW - Progesterone KW - 4G7DS2Q64Y KW - Abridged Index Medicus KW - Index Medicus KW - Diphosphonates -- therapeutic use KW - Ovariectomy -- adverse effects KW - Progesterone -- therapeutic use KW - Premenopause KW - Menopause, Premature KW - Humans KW - Adult KW - Progesterone -- adverse effects KW - Aged KW - Middle Aged KW - Lung -- physiopathology KW - Osteoporosis, Postmenopausal -- prevention & control KW - Female KW - Bone Density -- drug effects KW - Lung Neoplasms -- therapy KW - Lymphangioleiomyomatosis -- physiopathology KW - Lymphangioleiomyomatosis -- pathology KW - Lung Neoplasms -- physiopathology KW - Lymphangioleiomyomatosis -- therapy KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67350337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Bone+mineral+density+in+lymphangioleiomyomatosis.&rft.au=Taveira-Dasilva%2C+Angelo+M%3BStylianou%2C+Mario+P%3BHedin%2C+Carolyn+J%3BHathaway%2C+Olanda%3BMoss%2C+Joel&rft.aulast=Taveira-Dasilva&rft.aufirst=Angelo&rft.date=2005-01-01&rft.volume=171&rft.issue=1&rft.spage=61&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 - 2005-01-25 N1 - Date created - 2004-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Haplotype-based localization of an alcohol dependence gene to the 5q34 {gamma}-aminobutyric acid type A gene cluster. AN - 67338784; 15630072 AB - Pharmacobehavioral and pharmacogenetic evidence links gamma-aminobutyric acid type A (GABA(A)) receptors and chromosomal regions containing GABA(A) receptor genes to ethanol-related responses. The GABA(A) gene cluster on chromosome 5q34 is of particular interest in the genetics of alcohol dependence because of the gamma2 subunit requirement for ethanol's modulatory action on GABA(A) receptors, previous linkage findings in mice and humans implicating both GABRA6 and GABRG2, and reported associations of GABRA6, GABRB2, and GABRG2 alleles with alcohol dependence. To determine whether variation at the 5q34 GABA(A) gene cluster is implicated in differential susceptibility to alcohol dependence. Two large psychiatrically interviewed samples, a Southwestern Native American population sample (N = 433) and a Finnish sample (N = 511) with alcohol-dependent subjects and unaffected individuals, were genotyped for 6 single nucleotide polymorphisms at the 5q34 GABA(A) gene cluster. In addition to sib-pair linkage and case-control association analyses, linkage disequilibrium mapping with haplotypes was used. Sib-pair linkage of GABRG2 to alcohol dependence was observed in Finns (P = .008). Association of the GABRB2 1412T allele with alcohol dependence was detected in both populations (Finns, P = .01; Southwestern Native Americans, P = .008), and the GABRA6 1519T allele was associated in both Finns (P = .01) and Southwestern Native Americans (P = .03). Linkage disequilibrium mapping with 3-locus haplotypes yielded evidence for an alcohol-dependence locus at the GABA(A) gene cluster region in both populations. The most highly significant signals were at 3-locus haplotypes that included 1 or more GABRA6 polymorphisms, with the peak signal at a GABRA6 3-locus haplotype (Finns, empirical P = .004; Southwestern Native Americans, empirical P = .02). We detected sib-pair linkage of 5q34 GABA(A) receptor genes to alcohol dependence in Finns and found association both in Finns and in Southwestern Native Americans. In both populations, the haplotype localization implicates the region containing the Pro385Ser GABRA6 polymorphism and 2 other polymorphisms at GABRA6. JF - Archives of general psychiatry AU - Radel, Marta AU - Vallejo, Roger L AU - Iwata, Nakao AU - Aragon, Richard AU - Long, Jeffrey C AU - Virkkunen, Matti AU - Goldman, David AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA. martaradel@verizon.net Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 47 EP - 55 VL - 62 IS - 1 SN - 0003-990X, 0003-990X KW - Receptors, GABA-A KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Genetic Variation KW - Humans KW - Linkage Disequilibrium -- genetics KW - European Continental Ancestry Group -- genetics KW - Finland -- ethnology KW - Genotype KW - Polymerase Chain Reaction KW - Multigene Family -- genetics KW - Southwestern United States -- ethnology KW - Polymorphism, Restriction Fragment Length KW - Indians, South American -- genetics KW - Adult KW - Genetic Predisposition to Disease KW - Adolescent KW - Polymorphism, Single Nucleotide -- genetics KW - Female KW - Male KW - Receptors, GABA-A -- genetics KW - Haplotypes -- genetics KW - Chromosomes, Human, Pair 5 -- genetics KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67338784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Haplotype-based+localization+of+an+alcohol+dependence+gene+to+the+5q34+%7Bgamma%7D-aminobutyric+acid+type+A+gene+cluster.&rft.au=Radel%2C+Marta%3BVallejo%2C+Roger+L%3BIwata%2C+Nakao%3BAragon%2C+Richard%3BLong%2C+Jeffrey+C%3BVirkkunen%2C+Matti%3BGoldman%2C+David&rft.aulast=Radel&rft.aufirst=Marta&rft.date=2005-01-01&rft.volume=62&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-04 N1 - Date created - 2005-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of germ cell mutagenicity in male CYP2E1-null and wild-type mice treated with acrylamide: evidence supporting a glycidamide-mediated effect. AN - 67338672; 15355880 AB - Acrylamide is an animal carcinogen and probable human carcinogen present in appreciable amounts in heated carbohydrate-rich foodstuffs. It is also a germ cell mutagen, inducing dominant lethal mutations and heritable chromosomal translocations in postmeiotic sperm of treated mice. Acrylamide's affinity for male germ cells has sometimes been overlooked in assessing its toxicity and defining human health risks. Previous investigations of acrylamide's germ cell activity in mice showed stronger effects after repeated administration of low doses compared with a single high dose, suggesting the possible involvement of a stable metabolite. A key oxidative metabolite of acrylamide is the epoxide glycidamide, generated by cytochrome P4502E1 (CYP2E1). To explore the role of CYP2E1 metabolism in the germ cell mutagenicity of acrylamide, CYP2E1-null and wild-type male mice were treated by intraperitoneal injection with 0, 12.5, 25, or 50 mg acrylamide (5 ml saline)(-1) kg(-1) day(-1) for 5 consecutive days. At defined times after exposure, males were mated to untreated B6C3F1 females. Females were killed in late gestation and uterine contents were examined. Dose-related increases in resorption moles (chromosomally aberrant embryos) and decreases in the numbers of pregnant females and the proportion of living fetuses were seen in females mated to acrylamide-treated wild-type mice. No changes in any fertility parameters were seen in females mated to acrylamide-treated CYP2E1-null mice. Our results constitute the first unequivocal demonstration that acrylamide-induced germ cell mutations in male mice require CYP2E1-mediated epoxidation of acrylamide. Thus, CYP2E1 polymorphisms in human populations, resulting in variable enzyme metabolic activities, may produce differential susceptibilities to acrylamide toxicities. JF - Biology of reproduction AU - Ghanayem, B I AU - Witt, K L AU - El-Hadri, L AU - Hoffler, U AU - Kissling, G E AU - Shelby, M D AU - Bishop, J B AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. ghanayem@niehs.nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 157 EP - 163 VL - 72 IS - 1 SN - 0006-3363, 0006-3363 KW - Acrylamides KW - 0 KW - Mutagens KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Index Medicus KW - Animals KW - Embryo Implantation KW - Animals, Inbred Strains KW - Fetal Development -- drug effects KW - Mice KW - Pregnancy KW - Pregnancy Rate KW - Mice, Mutant Strains KW - Mutagenicity Tests KW - Fetal Development -- genetics KW - Genes, Lethal KW - Female KW - Male KW - Spermatozoa -- physiology KW - Spermatozoa -- drug effects KW - Acrylamides -- toxicity KW - Mutagens -- toxicity KW - Mutation KW - Cytochrome P-450 CYP2E1 -- genetics KW - Cytochrome P-450 CYP2E1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67338672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Comparison+of+germ+cell+mutagenicity+in+male+CYP2E1-null+and+wild-type+mice+treated+with+acrylamide%3A+evidence+supporting+a+glycidamide-mediated+effect.&rft.au=Ghanayem%2C+B+I%3BWitt%2C+K+L%3BEl-Hadri%2C+L%3BHoffler%2C+U%3BKissling%2C+G+E%3BShelby%2C+M+D%3BBishop%2C+J+B&rft.aulast=Ghanayem&rft.aufirst=B&rft.date=2005-01-01&rft.volume=72&rft.issue=1&rft.spage=157&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 - 2005-07-19 N1 - Date created - 2004-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of functional D2 receptors prevents the effects of the D3-preferring agonist (+)-PD 128907 on dialysate dopamine levels. AN - 67338173; 15617726 AB - Substantial pharmacological evidence is consistent with an inhibitory effect of D3 receptor activation on dopamine (DA) release. Although receptor selectivity of the ligands employed in initial studies has been questioned, studies employing new, more selective, compounds continue to support an involvement of this receptor subtype in regulating extracellular dopamine levels in the dorsal striatum and nucleus accumbens. Consistent with this hypothesis, microdialysis studies have shown that the dose-effect curve for (+)-PD 128907, a moderately selective D3 agonist, is shifted to the right in D3 knock out mice. The present microdialysis studies sought to further examine the role of D2 vs. D3 receptors in mediating (+)-PD 128907-evoked alterations in basal and depolarization-evoked DA levels. Dialysate DA levels were determined in D2 knock out mice and wild type littermate controls following both systemic and local administration of (+)-PD 128907. In view of regional differences in D3 receptor localization, studies were conducted in the nucleus accumbens, a D3 receptor rich area, and in the dorsal striatum, a region with low D3 receptor abundance. Systemic or reverse dialysis of (+)-PD 128907 into the nucleus accumbens significantly decreased basal and depolarization-evoked DA levels in wild type mice. A similar effect was observed in the dorsal striatum. Regardless of the route of administration, (+)-PD 128907 was ineffective in modulating DA levels in either brain region of D2 knock out mice. These data contrast with previous results in D3 knock out mice and indicate that the D2 receptor is necessary for the inhibition of presynaptic DA neurotransmission produced by a preferential D3 agonist. Based on the documented physical interaction of D2 and D3 receptors in heterologous expression systems, we put forth a hypothesis that reconciles the seemingly paradoxical results of this and previous microdialysis studies. JF - Neuropharmacology AU - Zapata, Agustin AU - Shippenberg, Toni S AD - Integrative Neuroscience Section, Behavioral Neuroscience Branch, National Institute on Drug Abuse Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. azapata@intra.nida.nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 43 EP - 50 VL - 48 IS - 1 SN - 0028-3908, 0028-3908 KW - Benzopyrans KW - 0 KW - Dialysis Solutions KW - Drd3 protein, mouse KW - Oxazines KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D3 KW - 3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol KW - 123594-64-9 KW - Potassium Chloride KW - 660YQ98I10 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Drug Interactions KW - Potassium Chloride -- pharmacology KW - Mice KW - Microdialysis -- methods KW - Mice, Knockout KW - Electrochemistry -- methods KW - Chromatography, High Pressure Liquid -- methods KW - Dialysis Solutions -- metabolism KW - Mice, Inbred C57BL KW - Basal Ganglia -- drug effects KW - Receptors, Dopamine D2 -- deficiency KW - Brain Chemistry -- drug effects KW - Receptors, Dopamine D2 -- agonists KW - Benzopyrans -- pharmacology KW - Dopamine -- metabolism KW - Receptors, Dopamine D2 -- genetics KW - Oxazines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67338173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=Lack+of+functional+D2+receptors+prevents+the+effects+of+the+D3-preferring+agonist+%28%2B%29-PD+128907+on+dialysate+dopamine+levels.&rft.au=Zapata%2C+Agustin%3BShippenberg%2C+Toni+S&rft.aulast=Zapata&rft.aufirst=Agustin&rft.date=2005-01-01&rft.volume=48&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-28 N1 - Date created - 2004-12-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-additive carcinogenicity of a defined mixture of "dioxin-like compounds". AN - 67337575; 15626646 AB - Use of the dioxin toxic equivalency factor (TEF) approach in human risk assessments assumes that the combined effects of dioxin-like compounds in a mixture can be predicted based on a potency-adjusted dose-additive combination of constituents of the mixture. In this study, we evaluated the TEF approach in experimental 2-year rodent cancer bioassays with female Harlan Sprague-Dawley rats receiving 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3 ,4,4 ,5-pentachlorobiphenyl (PCB-126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of the three compounds. Statistically based dose-response modeling indicated that the shape of the dose-response curves for hepatic, lung, and oral mucosal neoplasms was the same in studies of the three individual chemicals and the mixture. In addition, the dose response for the mixture could be predicted from a combination of the potency-adjusted doses of the individual compounds. Finally, we showed that use of the current World Health Organization dioxin TEF values adequately predicted the increased incidence of liver tumors (hepatocellular adenoma and cholangiocarcinoma) induced by exposure to the mixture. These data support the use of the TEF approach for dioxin cancer risk assessments. JF - Environmental health perspectives AU - Walker, Nigel J AU - Crockett, Patrick W AU - Nyska, Abraham AU - Brix, Amy E AU - Jokinen, Michael P AU - Sells, Donald M AU - Hailey, James R AU - Easterling, Micheal AU - Haseman, Joseph K AU - Yin, Ming AU - Wyde, Michael E AU - Bucher, John R AU - Portier, Christopher J AD - National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27705, USA. walker3@niehs.nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 43 EP - 48 VL - 113 IS - 1 SN - 0091-6765, 0091-6765 KW - Carcinogens KW - 0 KW - Dioxins KW - Environmental Pollutants KW - Polychlorinated Dibenzodioxins KW - Index Medicus KW - Rats KW - Animals KW - Reference Values KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Humans KW - Polychlorinated Dibenzodioxins -- administration & dosage KW - Environmental Pollutants -- poisoning KW - Biological Assay KW - Polychlorinated Dibenzodioxins -- poisoning KW - Environmental Pollutants -- administration & dosage KW - Female KW - Risk Assessment KW - Mouth Neoplasms -- chemically induced KW - Dioxins -- poisoning KW - Lung Neoplasms -- veterinary KW - Mouth Neoplasms -- veterinary KW - Liver Neoplasms -- veterinary KW - Carcinogens -- administration & dosage KW - Liver Neoplasms -- chemically induced KW - Dioxins -- administration & dosage KW - Lung Neoplasms -- chemically induced KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67337575?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Dose-additive+carcinogenicity+of+a+defined+mixture+of+%22dioxin-like+compounds%22.&rft.au=Walker%2C+Nigel+J%3BCrockett%2C+Patrick+W%3BNyska%2C+Abraham%3BBrix%2C+Amy+E%3BJokinen%2C+Michael+P%3BSells%2C+Donald+M%3BHailey%2C+James+R%3BEasterling%2C+Micheal%3BHaseman%2C+Joseph+K%3BYin%2C+Ming%3BWyde%2C+Michael+E%3BBucher%2C+John+R%3BPortier%2C+Christopher+J&rft.aulast=Walker&rft.aufirst=Nigel&rft.date=2005-01-01&rft.volume=113&rft.issue=1&rft.spage=43&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 - 2005-03-22 N1 - Date created - 2004-12-31 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 2003 Apr 17;422(6933):681-7 [12700752] Toxicol Sci. 2003 Jul;74(1):182-91 [12730615] Science. 2004 Jan 9;303(5655):226-9 [14716013] Toxicol Appl Pharmacol. 2004 Jan 15;194(2):156-68 [14736496] Toxicol Appl Pharmacol. 1978 Nov;46(2):279-303 [734660] Biometrics. 1988 Jun;44(2):417-31 [3390507] Environ Health Perspect. 1998 Dec;106(12):775-92 [9831538] Pharmacol Toxicol. 1991 Dec;69(6):450-8 [1766921] Eur J Pharmacol. 1992 Dec 1;228(4):179-99 [1335882] Toxicology. 1995 Dec 28;105(2-3):391-401 [8571375] Annu Rev Cell Dev Biol. 1996;12:55-89 [8970722] Toxicol Appl Pharmacol. 1997 Dec;147(2):267-80 [9439722] Crit Rev Toxicol. 1990;21(1):51-88 [2124811] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bayesian latent variable models for mixed discrete outcomes. AN - 67336645; 15618524 AB - In studies of complex health conditions, mixtures of discrete outcomes (event time, count, binary, ordered categorical) are commonly collected. For example, studies of skin tumorigenesis record latency time prior to the first tumor, increases in the number of tumors at each week, and the occurrence of internal tumors at the time of death. Motivated by this application, we propose a general underlying Poisson variable framework for mixed discrete outcomes, accommodating dependency through an additive gamma frailty model for the Poisson means. The model has log-linear, complementary log-log, and proportional hazards forms for count, binary and discrete event time outcomes, respectively. Simple closed form expressions can be derived for the marginal expectations, variances, and correlations. Following a Bayesian approach to inference, conditionally-conjugate prior distributions are chosen that facilitate posterior computation via an MCMC algorithm. The methods are illustrated using data from a Tg.AC mouse bioassay study. JF - Biostatistics (Oxford, England) AU - Dunson, David B AU - Herring, Amy H AD - Biostatistics Branch, National Institute of Environmental Health Sciences, MD A3-03, PO Box 12233, Research Triangle Park, NC 27709, USA. dunson1@niehs.nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 11 EP - 25 VL - 6 IS - 1 SN - 1465-4644, 1465-4644 KW - Acrylates KW - 0 KW - Organic Chemicals KW - Propylene Glycols KW - pentaerythrityl triacrylate KW - PJJ1161ULF KW - Index Medicus KW - Animals KW - Computer Simulation KW - Organic Chemicals -- toxicity KW - Mice KW - Poisson Distribution KW - Acrylates -- toxicity KW - Mice, Transgenic KW - Monte Carlo Method KW - Skin Neoplasms -- chemically induced KW - Propylene Glycols -- toxicity KW - Markov Chains KW - Papilloma -- chemically induced KW - Proportional Hazards Models KW - Bayes Theorem KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67336645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biostatistics+%28Oxford%2C+England%29&rft.atitle=Bayesian+latent+variable+models+for+mixed+discrete+outcomes.&rft.au=Dunson%2C+David+B%3BHerring%2C+Amy+H&rft.aulast=Dunson&rft.aufirst=David&rft.date=2005-01-01&rft.volume=6&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Biostatistics+%28Oxford%2C+England%29&rft.issn=14654644&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-24 N1 - Date created - 2004-12-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Response to 5% carbon dioxide in children and adolescents: relationship to panic disorder in parents and anxiety disorders in subjects. AN - 67335700; 15630075 AB - Carbon dioxide (CO(2)) sensitivity is postulated to be a familial risk marker of panic disorder (PD). Exaggerated responses to CO(2) inhalation have been reported in adults with PD and their unaffected adult relatives, as well as in clinic-referred children with anxiety disorders. To test in a family-based design whether CO(2) hypersensitivity is a familial risk marker for PD and associated with current anxiety disorders in children and adolescents. One hundred forty-two offspring (aged 9-19 years) of parents with PD, major depressive disorder, or no disorder. Forty-five (32%) had a current anxiety disorder, excluding specific phobia. Parents and offspring received diagnostic assessments. Offspring underwent 5% CO(2) inhalation at home. Panic symptoms and panic attacks were rated with the Acute Panic Inventory at baseline, while anticipating CO(2) delivery ("threat"), and during CO(2) inhalation. Respiratory rate and volume were measured with spirometry. No group differences were found in Acute Panic Inventory ratings at baseline or in respiratory measures during threat. Risk for PD was not associated with CO(2) sensitivity (panic symptoms and respiratory physiologic response). During CO(2) inhalation, offspring with anxiety disorders, relative to offspring without anxiety disorders, experienced significantly more panic symptoms and panic attacks, as well as elevated respiratory rates. During threat, panic symptoms were significantly and independently associated with both parental PD and offspring anxiety disorders. No support was obtained for CO(2) hypersensitivity as a familial risk marker for PD in children and adolescents. Links between childhood anxiety disorders and CO(2) sensitivity were replicated. Familial risk for PD in children and adolescents may be associated with vulnerability to anticipatory anxiety. JF - Archives of general psychiatry AU - Pine, Daniel S AU - Klein, Rachel G AU - Roberson-Nay, Roxann AU - Mannuzza, Salvatore AU - Moulton, John L AU - Woldehawariat, Girma AU - Guardino, Mary AD - Section on Development and Affective Neuroscience, National Institute of Mental Health Intramural Research Program, Bethesda, MD 20817, USA. daniel.pine@nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 73 EP - 80 VL - 62 IS - 1 SN - 0003-990X, 0003-990X KW - Genetic Markers KW - 0 KW - Carbon Dioxide KW - 142M471B3J KW - Abridged Index Medicus KW - Index Medicus KW - Age Factors KW - Psychiatric Status Rating Scales KW - Respiratory Physiological Phenomena -- drug effects KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Adult KW - Personality Inventory KW - Child KW - Adolescent KW - Panic Disorder -- chemically induced KW - Anxiety Disorders -- genetics KW - Carbon Dioxide -- administration & dosage KW - Anxiety Disorders -- diagnosis KW - Anxiety Disorders -- chemically induced KW - Child of Impaired Parents KW - Panic Disorder -- genetics KW - Carbon Dioxide -- pharmacology KW - Panic Disorder -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67335700?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Response+to+5%25+carbon+dioxide+in+children+and+adolescents%3A+relationship+to+panic+disorder+in+parents+and+anxiety+disorders+in+subjects.&rft.au=Pine%2C+Daniel+S%3BKlein%2C+Rachel+G%3BRoberson-Nay%2C+Roxann%3BMannuzza%2C+Salvatore%3BMoulton%2C+John+L%3BWoldehawariat%2C+Girma%3BGuardino%2C+Mary&rft.aulast=Pine&rft.aufirst=Daniel&rft.date=2005-01-01&rft.volume=62&rft.issue=1&rft.spage=73&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-04 N1 - Date created - 2005-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment. AN - 67335353; 15626454 AB - Despite years of research, delayed cerebral vasospasm remains the feared complication of a ruptured intracranial aneurysm. Worldwide effort has led to many promising experimental treatments that reverse or prevent cerebral vasospasm but none were confirmed to be effective in clinical trials. There are several sources for this failure: (1) the pathophysiology of delayed cerebral vasospasm remains poorly understood, (2) many experimental models of subarachnoid hemorrhage (SAH) do not mimic the actual clinical entity, and (3) many researchers erroneously extrapolate the data of peripheral and cerebral vascular physiological responses to the post-SAH situation. Thus, to explain the uniqueness of vasospasm and to address nitric oxide (NO) involvement in delayed vasospasm development, the following issues are addressed in this paper: (1) pathophysiological mechanisms of vasospasm, (2) NO-related contribution to its development. In addition, (3) a two-stage hypothesis of pathogenesis of delayed cerebral vasospasm is presented developed in the Vascular Laboratory of Surgical Neurology Branch of the National Institute of Neurological Disorders and Stroke using a primate model of SAH. According to this hypothesis, initially (Phase I) NO-releasing neurons are destroyed by oxyhemoglobin (oxyHb) leading to diminished availability of NO in the vessel wall and constriction of the vessels (Phase I). Increased shear stress evoked by narrowing of the arterial lumen should stimulate endothelial nitric oxide synthase (eNOS). But further metabolism of hemoglobin to bilirubin oxidized fragments (BOXes) increases asymmetric dimethylarginine (ADMA), an endogenous inhibitor of eNOS, in the vicinity of the artery further decreasing of NO availability and sustaining vasospasm (Phase II). In Phase III, the resolution of vasospasm, elimination of BOXes increases NO production by eNOS resulting in recovery of dilatory activity of endothelium. This hypothesis suggests that the key treatment to prevent delayed cerebral vasospasm should be focused on preventing oxyHb neurotoxicity, inhibiting BOX production, and exogenous NO delivery. JF - Pharmacology & therapeutics AU - Pluta, Ryszard M AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, 10 Center Drive, Room 5D37, MD 20892, USA. rysiek@ninds.nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 23 EP - 56 VL - 105 IS - 1 SN - 0163-7258, 0163-7258 KW - Nitric Oxide KW - 31C4KY9ESH KW - Index Medicus KW - Animals KW - Humans KW - Intracranial Aneurysm -- complications KW - Subarachnoid Hemorrhage -- complications KW - Vasospasm, Intracranial -- physiopathology KW - Vasospasm, Intracranial -- prevention & control KW - Vasospasm, Intracranial -- etiology KW - Nitric Oxide -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67335353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Delayed+cerebral+vasospasm+and+nitric+oxide%3A+review%2C+new+hypothesis%2C+and+proposed+treatment.&rft.au=Pluta%2C+Ryszard+M&rft.aulast=Pluta&rft.aufirst=Ryszard&rft.date=2005-01-01&rft.volume=105&rft.issue=1&rft.spage=23&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 - 2005-04-29 N1 - Date created - 2004-12-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental PCB exposure and risk of endometriosis. AN - 67327353; 15513976 AB - Hormonally active environmental agents have recently been associated with the development of endometriosis. We undertook a study to assess the relationship between endometriosis, an estrogen-dependent gynaecological disease, and 62 individual polychlorinated biphenyl (PCBs) congeners. We enrolled 84 eligible women aged 18-40 years undergoing laparoscopy for study, which included an interview and blood specimen (n=79; 94%). Thirty-two women had visually confirmed endometriosis at laparoscopy while 52 did not. Blood specimens were run in batches of 14 including four quality control samples for toxicological analysis. Each PCB congener was adjusted for recovery; batch-specific reagent blanks were subtracted. All PCB concentrations were log transformed and expressed in ng/g serum first as a sum and then as tertiles by purported estrogenic or anti-estrogenic activity of PCB congeners. Using unconditional logistic regression analysis, a significantly elevated odds ratio (OR) was observed for women in the third tertile of anti-estrogenic PCBs [OR 3.77; 95% confidence interval (CI) 1.12-12.68]. Risk remained elevated after controlling for gravidity, current cigarette smoking and serum lipids (OR 3.30; 95% CI 0.87-12.46). These data suggest that anti-estrogenic PCBs may be associated with the development of endometriosis. JF - Human reproduction (Oxford, England) AU - Louis, G M Buck AU - Weiner, J M AU - Whitcomb, B W AU - Sperrazza, R AU - Schisterman, E F AU - Lobdell, D T AU - Crickard, K AU - Greizerstein, H AU - Kostyniak, P J AD - Epidemiology Branch, Division of Epidemiology, Statistics & Prevention Research, National Institute of Child Health & Human Development, Rockville, MD 20852, USA. gb156i@nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 279 EP - 285 VL - 20 IS - 1 SN - 0268-1161, 0268-1161 KW - Environmental Pollutants KW - 0 KW - Estrogen Receptor Modulators KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Odds Ratio KW - Risk Factors KW - Humans KW - Cohort Studies KW - Adult KW - Adolescent KW - Female KW - Endometriosis -- blood KW - Estrogen Receptor Modulators -- toxicity KW - Environmental Pollutants -- toxicity KW - Estrogen Receptor Modulators -- chemistry KW - Polychlorinated Biphenyls -- toxicity KW - Polychlorinated Biphenyls -- chemistry KW - Polychlorinated Biphenyls -- blood KW - Estrogen Receptor Modulators -- blood KW - Endometriosis -- etiology KW - Environmental Pollutants -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67327353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Environmental+PCB+exposure+and+risk+of+endometriosis.&rft.au=Louis%2C+G+M+Buck%3BWeiner%2C+J+M%3BWhitcomb%2C+B+W%3BSperrazza%2C+R%3BSchisterman%2C+E+F%3BLobdell%2C+D+T%3BCrickard%2C+K%3BGreizerstein%2C+H%3BKostyniak%2C+P+J&rft.aulast=Louis&rft.aufirst=G+M&rft.date=2005-01-01&rft.volume=20&rft.issue=1&rft.spage=279&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 - 2005-06-13 N1 - Date created - 2004-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacological and toxicological evaluation of 2-fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-F-A-85380), a ligand for imaging cerebral nicotinic acetylcholine receptors with positron emission tomography. AN - 67323920; 15331657 AB - 2-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[(18)F]F-A-85380), a positron emission tomography (PET) radioligand for neuronal alpha4beta2(*) nicotinic acetylcholine receptors, was evaluated for its pharmacology and safety. In the Ames test for mutagenicity, 2-F-A-85380 was without effect in five bacterial strains. No evidence of gross pathology or histopathological changes occurred in either 2-day acute (0.4-4000 nmol/kg i.v.) or 14-day expanded acute (40-4000 nmol/kg i.v.) toxicity studies in mice. Similarly, hematology and serum chemistry values in rhesus monkeys administered 60 nmol/kg i.v. were not affected over 14 days. Like nicotine, 2-F-A-85380 produced convulsions in mice at very high doses. The ED(50) value of 2-F-A-85380 for eliciting tonic-clonic convulsions (5.0 micromol/kg i.v.) was nearly 4 times greater than that of nicotine (ED(50) = 1.4 micromol/kg i.v.). Lower doses of 2-F-A-85380 (30-300 nmol/kg i.v.) and nicotine (20-400 nmol/kg i.v.) increased systolic and diastolic blood pressure, heart rate, and cardiac contractility in rats. Notably, the PR, QRS, or QTc intervals of the rat electrocardiogram were unaffected by either drug. Dosimetry studies indicated that the urinary bladder wall was the critical organ and total radiation exposure was within acceptable limits. Estimated doses of 2-F-A-85380 required to elevate blood pressure and heart rate by 10% ranged from 40 to 58 nmol/kg i.v. Nevertheless, the estimated radiopharmaceutically relevant dose of [(18)F]2-F-A-8380 required for initial PET imaging studies, 10 pmol/kg, is less than 1/4000th of the doses calculated (40-58 nmol/kg i.v.) to elevate blood pressure and heart rate by 10% in humans and should elicit no clinically significant effects and have acceptable dosimetry. JF - The Journal of pharmacology and experimental therapeutics AU - Vaupel, D Bruce AU - Tella, Srihari R AU - Huso, David L AU - Wagner, Valentine O AU - Mukhin, Alexey G AU - Chefer, Svetlana I AU - Horti, Andrew G AU - London, Edythe D AU - Koren, Andrei O AU - Kimes, Alane S AD - NIDA IRP, Neuroimaging Research Branch, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. bvaupel@intra.nida.nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 355 EP - 365 VL - 312 IS - 1 SN - 0022-3565, 0022-3565 KW - 2-fluoro-3-(2(S)-azetidinylmethoxy)pyridine KW - 0 KW - Convulsants KW - Fluorine Radioisotopes KW - Pyridines KW - Receptors, Nicotinic KW - Index Medicus KW - Animals KW - Positron-Emission Tomography KW - Body Temperature -- drug effects KW - Dose-Response Relationship, Drug KW - Myocardial Contraction -- drug effects KW - Mice KW - Cardiovascular System -- drug effects KW - Primates KW - Convulsants -- toxicity KW - Rats KW - Behavior, Animal -- drug effects KW - Rats, Sprague-Dawley KW - Heart Rate -- drug effects KW - Body Weight -- drug effects KW - Motor Activity -- drug effects KW - Blood Pressure -- drug effects KW - Male KW - Female KW - Electrocardiography -- drug effects KW - Cerebral Cortex -- metabolism KW - Receptors, Nicotinic -- metabolism KW - Pyridines -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67323920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Pharmacological+and+toxicological+evaluation+of+2-fluoro-3-%282%28S%29-azetidinylmethoxy%29pyridine+%282-F-A-85380%29%2C+a+ligand+for+imaging+cerebral+nicotinic+acetylcholine+receptors+with+positron+emission+tomography.&rft.au=Vaupel%2C+D+Bruce%3BTella%2C+Srihari+R%3BHuso%2C+David+L%3BWagner%2C+Valentine+O%3BMukhin%2C+Alexey+G%3BChefer%2C+Svetlana+I%3BHorti%2C+Andrew+G%3BLondon%2C+Edythe+D%3BKoren%2C+Andrei+O%3BKimes%2C+Alane+S&rft.aulast=Vaupel&rft.aufirst=D&rft.date=2005-01-01&rft.volume=312&rft.issue=1&rft.spage=355&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 - 2005-04-13 N1 - Date created - 2004-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ebola virus glycoprotein toxicity is mediated by a dynamin-dependent protein-trafficking pathway. AN - 67322858; 15596847 AB - Ebola virus infection causes a highly lethal hemorrhagic fever syndrome associated with profound immunosuppression through its ability to induce widespread inflammation and cellular damage. Though GP, the viral envelope glycoprotein, mediates many of these effects, the molecular events that underlie Ebola virus cytopathicity are poorly understood. Here, we define a cellular mechanism responsible for Ebola virus GP cytotoxicity. GP selectively decreased the expression of cell surface molecules that are essential for cell adhesion and immune function. GP dramatically reduced levels of alphaVbeta3 without affecting the levels of alpha2beta1 or cadherin, leading to cell detachment and death. This effect was inhibited in vitro and in vivo by brefeldin A and was dependent on dynamin, the GTPase. GP also decreased cell surface expression of major histocompatibility complex class I molecules, which alters recognition by immune cells, and this effect was also dependent on the mucin domain previously implicated in GP cytotoxicity. By altering the trafficking of select cellular proteins, Ebola virus GP inflicts cell damage and may facilitate immune escape by the virus. JF - Journal of virology AU - Sullivan, Nancy J AU - Peterson, Mary AU - Yang, Zhi-yong AU - Kong, Wing-pui AU - Duckers, Heinricus AU - Nabel, Elizabeth AU - Nabel, Gary J AD - Vaccine Research Center, National Institute for Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20814, USA. Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 547 EP - 553 VL - 79 IS - 1 SN - 0022-538X, 0022-538X KW - Histocompatibility Antigens Class I KW - 0 KW - Integrin alphaVbeta3 KW - Mucins KW - Viral Envelope Proteins KW - envelope glycoprotein, Ebola virus KW - Dynamins KW - EC 3.6.5.5 KW - Index Medicus KW - Swine KW - Carotid Arteries KW - Animals KW - Endothelium, Vascular -- cytology KW - Down-Regulation KW - Transfection KW - Mucins -- metabolism KW - Humans KW - Endothelium, Vascular -- pathology KW - Dynamins -- metabolism KW - Histocompatibility Antigens Class I -- metabolism KW - Integrin alphaVbeta3 -- metabolism KW - Ebolavirus -- pathogenicity KW - Ebolavirus -- metabolism KW - Viral Envelope Proteins -- toxicity KW - Viral Envelope Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67322858?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Ebola+virus+glycoprotein+toxicity+is+mediated+by+a+dynamin-dependent+protein-trafficking+pathway.&rft.au=Sullivan%2C+Nancy+J%3BPeterson%2C+Mary%3BYang%2C+Zhi-yong%3BKong%2C+Wing-pui%3BDuckers%2C+Heinricus%3BNabel%2C+Elizabeth%3BNabel%2C+Gary+J&rft.aulast=Sullivan&rft.aufirst=Nancy&rft.date=2005-01-01&rft.volume=79&rft.issue=1&rft.spage=547&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 - 2005-01-14 N1 - Date created - 2004-12-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 2000 Dec 5;278(1):20-6 [11112476] J Cell Biol. 1998 Apr 6;141(1):101-14 [9531551] J Virol. 2002 Mar;76(5):2518-28 [11836430] Science. 1998 Feb 13;279(5353):1034-7 [9461435] J Comp Neurol. 1997 Jan 20;377(3):324-40 [8989649] Science. 1998 Apr 10;280(5361):248-53 [9535648] Nat Med. 1999 Apr;5(4):423-6 [10202932] Science. 1999 Aug 13;285(5430):1028-32 [10446041] Mol Med. 1999 Apr;5(4):224-31 [10448644] J Cell Biol. 1993 Aug;122(3):565-78 [8335685] J Immunol. 2000 Jan 15;164(2):953-8 [10623844] Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8051-6 [10859362] Nat Med. 2000 Aug;6(8):886-9 [10932225] J Gen Virol. 2000 Sep;81(Pt 9):2155-9 [10950971] J Immunol. 2000 Oct 15;165(8):4667-75 [11035110] Virology. 1994 Mar;199(2):469-73 [8122375] Science. 1994 Dec 16;266(5192):1865-9 [7997879] Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3602-7 [8622982] Science. 2001 Mar 9;291(5510):1965-9 [11239157] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Primate Retinal Signaling Pathways: Suppressing ON-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-NYX Genetic Night Blindness. AN - 67319411; 15331616 AB - Retinal on-pathway dysfunction is implicated in human complete-type congenital stationary night blindness (CSNB1), a Mendelian genetic condition that results from mutations in the NYX gene encoding the protein nyctalopin. We probed cone pathway dysfunction in four human genotyped CSNB1 affected males by electroretinogram (ERG) recordings elicited with photopic sinusoidal and rapid-on/off-ramp flicker stimuli that are reputed to elicit on/off-pathway activity selectively. Results were analyzed in relation to ERG abnormalities created in anesthetized non-human primates by intravitreal application of glutamate analogues that selectively suppress retinal on- or off-pathway bipolar cell activity. 2-amino-4-phosphonobutyric acid (APB), which selectively blocks light responses of on-pathway depolarizing bipolar cells, fully recreated the essential ERG abnormalities found for human CSNB1 under the condition that the off-pathway remained active. Both CSNB1-NYX humans and APB-treated monkey retina lacked the normal amplitude dip and the phase deflection that occurs in the fundamental component near 12 Hz for sinusoidal flicker stimuli. The off-pathway suppressing agent, cis-2,3-piperidine-dicarboxylic acid (PDA), gave results in monkey quite discordant to CSNB1 human for sinusoidal stimulation. The results implicated a specific on-pathway signaling deficiency in CSNB1-NYX males with no evidence of off-pathway involvement. Likewise, rapid-on/off ramping stimuli also indicated that the functional deficit was localized to the on pathway. Analysis of non-human primate retinal responses after drug application demonstrated a complexity to on/off-pathway contributions to ramping on/off ERG responses not previously anticipated. These results support the hypothesis that nyctalopin acts principally or exclusively within the on pathway at the level of depolarizing bipolar cells, and thus human CSNB1-NYX subjects provide an opportunity to probe the primate visual system for consequences of on-pathway deficits. JF - Journal of neurophysiology AU - Khan, Naheed W AU - Kondo, Mineo AU - Hiriyanna, Kelaginamane T AU - Jamison, Jeff A AU - Bush, Ronald A AU - Sieving, Paul A AD - National Eye Institute, Bldg 31 -Room 6A03,31 Center Drive, MSC 2510, Bethesda, MD 20892-2110, USA. Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 481 EP - 492 VL - 93 IS - 1 SN - 0022-3077, 0022-3077 KW - Aminobutyrates KW - 0 KW - Excitatory Amino Acid Agonists KW - Excitatory Amino Acid Antagonists KW - NYX protein, human KW - Pipecolic Acids KW - Proteoglycans KW - Glutamic Acid KW - 3KX376GY7L KW - 2,3-piperidinedicarboxylic acid KW - 46026-75-9 KW - 2-amino-4-phosphonobutyric acid KW - 6323-99-5 KW - Index Medicus KW - Animals KW - Drug Interactions KW - DNA Mutational Analysis -- methods KW - Humans KW - Dose-Response Relationship, Radiation KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Photic Stimulation KW - Aminobutyrates -- pharmacology KW - Electroretinography -- methods KW - Pipecolic Acids -- pharmacology KW - Adult KW - Excitatory Amino Acid Agonists -- pharmacology KW - Middle Aged KW - Macaca mulatta KW - Adolescent KW - Mutation KW - Male KW - Female KW - Proteoglycans -- genetics KW - Glutamic Acid -- analogs & derivatives KW - Retina -- drug effects KW - Visual Pathways -- physiopathology KW - Retina -- physiopathology KW - Night Blindness -- physiopathology KW - Glutamic Acid -- pharmacology KW - Visual Pathways -- drug effects KW - Night Blindness -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67319411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Primate+Retinal+Signaling+Pathways%3A+Suppressing+ON-Pathway+Activity+in+Monkey+With+Glutamate+Analogues+Mimics+Human+CSNB1-NYX+Genetic+Night+Blindness.&rft.au=Khan%2C+Naheed+W%3BKondo%2C+Mineo%3BHiriyanna%2C+Kelaginamane+T%3BJamison%2C+Jeff+A%3BBush%2C+Ronald+A%3BSieving%2C+Paul+A&rft.aulast=Khan&rft.aufirst=Naheed&rft.date=2005-01-01&rft.volume=93&rft.issue=1&rft.spage=481&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-28 N1 - Date created - 2004-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of myristoylated alanine-rich C kinase substrate (MARCKS) in astrocytes. AN - 67306979; 15574358 AB - We have characterized membrane-associated substrates of Ca2+-dependent kinases in primary rat astrocytes by in vitro phosphorylation, 2-dimensional gel electrophoresis and autoradiography. The most prominent among these were three acidic, protein kinase C (PKC) substrates. These are important because they likely transduce cytokine and other neuro-immune modulatory signals mediated by PKC. We now show that one of these phosphoproteins is myristoylated alanine-rich PKC kinase substrate (MARCKS) or phosphomyristin C. The identity was corroborated by one- and 2- dimensional immunoblotting with an MARCKS-specific polyclonal antibody. Exposing primary astrocytes to phorbol 12-myristate 13-acetate stimulated phosphorylation of this protein. The level of MARCKS appeared inversely proportional to the proliferative potential of astrocytes because it was lower in spontaneously transformed as compared to passaged or confluent cells. These data are consistent with previous reports and indicate that one of three major acidic membrane-associated PKC substrates in astrocytes is MARCKS. Thus, MARCKS is likely near-proximal transducer of PKC-mediated signals in astrocytes. JF - Frontiers in bioscience : a journal and virtual library AU - Vitkovic, Ljubisa AU - Aloyo, Vincent J AU - Maeda, Shigeru AU - Benzil, Deborha L AU - Bressler, Joseph P AU - Hilt, Dana C AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. vitkovic@hotmail.com Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - 160 EP - 165 VL - 10 SN - 1093-9946, 1093-9946 KW - Cytokines KW - 0 KW - GAP-43 Protein KW - Intracellular Signaling Peptides and Proteins KW - Membrane Proteins KW - myristoylated alanine-rich C kinase substrate KW - 125267-21-2 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Rats KW - Protein Kinase C -- metabolism KW - Neuroglia -- metabolism KW - Animals KW - Cells, Cultured KW - GAP-43 Protein -- chemistry KW - Electrophoresis, Gel, Two-Dimensional KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cytokines -- metabolism KW - Cell Membrane -- metabolism KW - Cell Proliferation KW - Autoradiography KW - Astrocytes -- cytology KW - Intracellular Signaling Peptides and Proteins -- metabolism KW - Membrane Proteins -- metabolism KW - Intracellular Signaling Peptides and Proteins -- physiology KW - Membrane Proteins -- physiology KW - Astrocytes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67306979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Identification+of+myristoylated+alanine-rich+C+kinase+substrate+%28MARCKS%29+in+astrocytes.&rft.au=Vitkovic%2C+Ljubisa%3BAloyo%2C+Vincent+J%3BMaeda%2C+Shigeru%3BBenzil%2C+Deborha+L%3BBressler%2C+Joseph+P%3BHilt%2C+Dana+C&rft.aulast=Vitkovic&rft.aufirst=Ljubisa&rft.date=2005-01-01&rft.volume=10&rft.issue=&rft.spage=160&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 - 2006-07-07 N1 - Date created - 2004-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of synthetic polymer on the filamentous bacteria in activated sludge. AN - 67276581; 15364077 AB - Filamentous bulking is one of the solid-liquid separation problems always seen in activated sludge process. The addition of synthetic polymer is always one of the popular ways for the treatment plant operator to immediately solve the poor sludge settling problem. Therefore, it may be interesting to understand the effects of synthetic polymer on the filamentous bacteria in activated sludge. In this study, synthetic polymer was applied to a lab-scale wastewater treatment system with the filamentous bulking problem. The population structure of filamentous bacteria and sludge characteristics were investigated under different conditions. When synthetic polymer was added into the system, it was found that poor sludge settleability caused by filamentous bulking was temporarily solved and filamentous branches growing outside the flocs were damaged or inhibited. However, filamentous growth was still observed inside the flocs. After the addition of polymer was halted, filamentous branches extended out of the flocs immediately. Very serious filamentous bulking occurred and sludge settleability became much worse than that occurring before the addition of polymer. And, it took several weeks for the system to return to normal operation. JF - Bioresource technology AU - Juang, Der-Fong 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 - 2005/01// PY - 2005 DA - January 2005 SP - 31 EP - 40 VL - 96 IS - 1 SN - 0960-8524, 0960-8524 KW - Polymers KW - 0 KW - Sewage KW - Index Medicus KW - Biodegradation, Environmental KW - Flocculation KW - Time Factors KW - Bacteria -- metabolism KW - Sewage -- analysis KW - Waste Disposal, Fluid -- instrumentation KW - Sewage -- microbiology KW - Bacteria -- growth & development KW - Waste Disposal, Fluid -- methods KW - Polymers -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67276581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioresource+technology&rft.atitle=Effects+of+synthetic+polymer+on+the+filamentous+bacteria+in+activated+sludge.&rft.au=Juang%2C+Der-Fong&rft.aulast=Juang&rft.aufirst=Der-Fong&rft.date=2005-01-01&rft.volume=96&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Bioresource+technology&rft.issn=09608524&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-08 N1 - Date created - 2004-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prevention and therapy of colorectal cancer. AN - 67266220; 15527810 AB - Colorectal cancer is expected to affect more than 146,000 and kill more than 57,000 Americans in 2004. Increased understanding of carcinogenesis is transforming clinical approaches to all stages of this disease. During the last 5 years, four new drugs have been approved for colorectal cancer treatment, and substantial progress has been made in identifying and developing agents that prevent or delay carcinogenesis. These advances substantiate target-driven approaches to cancer prevention and treatment, and provide fruitful opportunities for future investigations. JF - The Medical clinics of North America AU - Hawk, Ernest T AU - Umar, Asad AU - Richmond, Ellen AU - Viner, Jaye L AD - Gastrointestinal and Other Cancers Research Group, Division of Cancer Prevention, National Cancer Institute, EPN, Suite 2141, 6130 Executive Boulevard, Bethesda, MD 20892-7317, USA. eh51p@nih.gov Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 85 EP - 110, viii VL - 89 IS - 1 SN - 0025-7125, 0025-7125 KW - Abridged Index Medicus KW - Index Medicus KW - Neoplasm Staging KW - Humans KW - Cell Transformation, Neoplastic KW - Colorectal Neoplasms -- therapy KW - Colorectal Neoplasms -- physiopathology KW - Colorectal Neoplasms -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67266220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Medical+clinics+of+North+America&rft.atitle=Prevention+and+therapy+of+colorectal+cancer.&rft.au=Hawk%2C+Ernest+T%3BUmar%2C+Asad%3BRichmond%2C+Ellen%3BViner%2C+Jaye+L&rft.aulast=Hawk&rft.aufirst=Ernest&rft.date=2005-01-01&rft.volume=89&rft.issue=1&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=The+Medical+clinics+of+North+America&rft.issn=00257125&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-08 N1 - Date created - 2004-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurotrophins protect against cytosine arabinoside-induced apoptosis of immature rat cerebellar neurons. AN - 67258806; 15567516 AB - Neurotrophin-induced neuroprotection against apoptosis was investigated using immature cultured cerebellar granule cells (CGC) from newborn rat pups. Apoptotic cell death induced by treatment with cytosine arabinoside (AraC) was confirmed by DNA fragmentation and quantified by cell survival assays. AraC was most effective in inducing apoptosis when added to CGC on the day of culture preparation, while less or no effect was observed when added at 24 or 48h after plating, respectively. Pretreatment of CGC cultures for 24h with brain-derived neurotrophic factor (BDNF) or neurotrophin-4 (NT-4), but not neurotrophin-3 (NT-3), robustly protected against AraC neurotoxicity. K252a, an inhibitor of the tropomyosin-related kinase (Trk) tyrosine kinase receptor family which showed no toxicity by itself, blocked BDNF protection of AraC-induced apoptosis in a concentration-dependent manner. Neither protein kinase C activation nor inhibition mimicked or affected BDNF protection against AraC neurotoxicity. BDNF, but not NT-3, treatment of immature CGC caused a marked, but transient activation of Akt through phosphatidylinositol (PI) 3-kinase. The neuroprotective effects of BDNF were suppressed by pretreatment with LY 294002 (a PI 3-kinase inhibitor). BDNF neuroprotection was also preceded by activation of mitogen activated protein kinase (MAPK) and suppressed by two MAPK/ERK (MEK)-selective inhibitors, PD 98059 and U-0126. Moreover, inhibitors of PI 3-kinase and MEK potentiated AraC-induced neurotoxicity. These results show that neurotrophins protect against AraC-induced apoptosis, at least in part, through TrkB-mediated activation of the PI 3-kinase/Akt and MEK signaling pathways. JF - Neurochemistry international AU - Leeds, P AU - Leng, Y AU - Chalecka-Franaszek, E AU - Chuang, D-M AD - Molecular Neurobiology Section, National Institute of Mental Health/NIH, 10 Center Drive, MSC 1363, Bethesda, MD 20892-1363, USA. Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 61 EP - 72 VL - 46 IS - 1 SN - 0197-0186, 0197-0186 KW - Antimetabolites, Antineoplastic KW - 0 KW - Brain-Derived Neurotrophic Factor KW - Nerve Growth Factors KW - Proto-Oncogene Proteins KW - Cytarabine KW - 04079A1RDZ KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Akt1 protein, rat KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Protein Kinase C KW - EC 2.7.11.13 KW - MAP Kinase Kinase Kinases KW - EC 2.7.11.25 KW - neurotrophin 4 KW - P658DCA9XD KW - Index Medicus KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Proto-Oncogene Proteins -- metabolism KW - Rats KW - MAP Kinase Kinase Kinases -- metabolism KW - Protein Kinase C -- metabolism KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Cell Survival -- drug effects KW - Brain-Derived Neurotrophic Factor -- pharmacology KW - Cytoplasmic Granules -- drug effects KW - DNA Fragmentation KW - Cerebellum -- cytology KW - Nerve Growth Factors -- pharmacology KW - Cytarabine -- antagonists & inhibitors KW - Neurons -- drug effects KW - Cerebellum -- drug effects KW - Cytarabine -- toxicity KW - Apoptosis -- drug effects KW - Antimetabolites, Antineoplastic -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67258806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurochemistry+international&rft.atitle=Neurotrophins+protect+against+cytosine+arabinoside-induced+apoptosis+of+immature+rat+cerebellar+neurons.&rft.au=Leeds%2C+P%3BLeng%2C+Y%3BChalecka-Franaszek%2C+E%3BChuang%2C+D-M&rft.aulast=Leeds&rft.aufirst=P&rft.date=2005-01-01&rft.volume=46&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Neurochemistry+international&rft.issn=01970186&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-22 N1 - Date created - 2004-11-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Status of Health Services Research on Adjudicated Drug-Abusing Juveniles: Selected Findings and Remaining Questions AN - 61523522; 200505293 AB - This article focuses on the factors that affect the availability, accessibility, & opportunity of effective treatment for the adjudicated adolescent drug user. The social & developmental context of "drug abuse" & its treatment in adolescents, & particularly in adjudicated adolescents, is reviewed & compared with that in adults. Selected health services research findings on this population are discussed in terms of the effectiveness of delivering treatment services; the organization, management, & financing of services; & adoption of best practices (technology transfer). 101 References. Adapted from the source document. JF - Substance Use & Misuse AU - Flanzer, Jerry AD - Division Epidemiology, National Instit Drug Abuse, Bethesda, MD JF199I@nih.gov Y1 - 2005///0, PY - 2005 DA - 0, 2005 SP - 887 EP - 911 VL - 40 IS - 7 SN - 1082-6084, 1082-6084 KW - adolescents KW - drug abuse KW - juvenile justice KW - health services KW - recovery relapse, treatment effectiveness KW - Treatment Programs KW - Treatment Methods KW - Juvenile Justice KW - Adolescents KW - Drug Abuse KW - article KW - 6129: addiction KW - 6146: crime & corrections UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61523522?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Substance+Use+%26+Misuse&rft.atitle=The+Status+of+Health+Services+Research+on+Adjudicated+Drug-Abusing+Juveniles%3A+Selected+Findings+and+Remaining+Questions&rft.au=Flanzer%2C+Jerry&rft.aulast=Flanzer&rft.aufirst=Jerry&rft.date=2005-01-01&rft.volume=40&rft.issue=7&rft.spage=887&rft.isbn=&rft.btitle=&rft.title=Substance+Use+%26+Misuse&rft.issn=10826084&rft_id=info:doi/10.1081%2FJA-200058862 LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Number of references - 101 N1 - Last updated - 2016-09-28 N1 - CODEN - SUMIFL N1 - SubjectsTermNotLitGenreText - Adolescents; Juvenile Justice; Drug Abuse; Treatment Methods; Treatment Programs DO - http://dx.doi.org/10.1081/JA-200058862 ER - TY - JOUR T1 - Innovative Approaches to Measuring Outcomes and Providing Feedback: The Opioid Agonist Therapy Effectiveness (OpiATE) Initiative AN - 57199236; 200611926 AB - Nine Veterans Affairs (VA) opioid agonist therapy (OAT), or methadone maintenance, clinics were selected to participate in a multi-site facilitated quality improvement (QI) project focused on implementing evidence-based best practice guidelines. At baseline, project staff faced the challenge of developing a method for identifying and continuously monitoring clinical practices and associated outcomes of interest. The resulting method consisted of a Monthly Log used to track OAT patients and produce immediate, monthly performance feedback for clinic staff, and required minimal effort on the part of busy counseling staff. Combined with an educational toolkit and training, the QI package was named the Opioid Agonist Therapy Monitoring System (OMS). The OMS proved useful to clinics in tailoring and monitoring their QI efforts, and most clinics plan to continue using the revised stand-alone OMS after the project period ends. The following report describes the OMS and the evolution of the Monthly Log over a two-year period. 4 Figures, 28 References. Adapted from the source document. COPIES ARE AVAILABLE FROM: HAWORTH DOCUMENT DELIVERY CENTER, The Haworth Press, Inc., 10 Alice Street, Binghamton, NY 13904-1580 JF - Journal of Maintenance in the Addictions AU - Willenbring, Mark L AU - Postier, Andrea C AU - Kenny, Marie E AU - Hagedorn, Hildi J AD - Division Treatment & Recovery Research, NIAAA/National Instit. Health, Bethesda, MD Y1 - 2005///0, PY - 2005 DA - 0, 2005 SP - 13 EP - 32 PB - Haworth Press, Binghamton NY VL - 3 IS - 1 SN - 1091-1332, 1091-1332 KW - Outcome process and assessment (health care), health care evaluation mechanisms, treatment outcomes, opiate addiction and opiate dependence KW - Clinical outcomes KW - Methadone KW - Opioids KW - Monitoring KW - Drug addiction KW - Quality management KW - article UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57199236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Maintenance+in+the+Addictions&rft.atitle=Innovative+Approaches+to+Measuring+Outcomes+and+Providing+Feedback%3A+The+Opioid+Agonist+Therapy+Effectiveness+%28OpiATE%29+Initiative&rft.au=Willenbring%2C+Mark+L%3BPostier%2C+Andrea+C%3BKenny%2C+Marie+E%3BHagedorn%2C+Hildi+J&rft.aulast=Willenbring&rft.aufirst=Mark&rft.date=2005-01-01&rft.volume=3&rft.issue=1&rft.spage=13&rft.isbn=&rft.btitle=&rft.title=Journal+of+Maintenance+in+the+Addictions&rft.issn=10911332&rft_id=info:doi/10.1300%2FJ126v03n01_03 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2006-07-28 N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Opioids; Methadone; Clinical outcomes; Drug addiction; Quality management; Monitoring DO - http://dx.doi.org/10.1300/J126v03n01_03 ER - TY - JOUR T1 - Predicting individual differences in attention, memory, and planning in first graders from experiences at home, child care, and school AN - 57134465; 348251 AB - This study adds to the growing literature linking children's experiences in the environment to individual differences in their developing skills' in attention, memory, and planning. The authors asked about the extent to which stimulating and sensitive care in the family and in the child-care or school environments would predict these cognitive outcomes. The authors also questioned the primacy of experiences in the first 3 years of life. Data from a sample of 700 first graders whose experiences in the home and in child care or school were evaluated since early infancy revealed that the cumulative quality of the child-rearing environment was related to attention and memory but not to planning and that the quality of the family environment was more strongly associated with outcomes than was the quality of child care and of school. The quality of both children's early (6 through 36 months) and later (54 months and first grade) environments predicted performance on the attention and memory tasks. (Original abstract) JF - Developmental Psychology AU - NICHD Early Child Care Research Network AD - NICHD Early Child Care Research Network Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 99 EP - 114 VL - 41 IS - 1 SN - 0012-1649, 0012-1649 KW - Early life experiences KW - Predictors KW - Young children KW - Home environment KW - Memory functioning KW - Cognitive development KW - Child care KW - Attentional processes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57134465?accountid=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=Predicting+individual+differences+in+attention%2C+memory%2C+and+planning+in+first+graders+from+experiences+at+home%2C+child+care%2C+and+school&rft.au=NICHD+Early+Child+Care+Research+Network&rft.aulast=NICHD+Early+Child+Care+Research+Network&rft.aufirst=&rft.date=2005-01-01&rft.volume=41&rft.issue=1&rft.spage=99&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 - 2005-06-13 N1 - Document feature - refs. tbls. N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Young children; Cognitive development; Attentional processes; Memory functioning; Predictors; Home environment; Early life experiences; Child care ER - TY - JOUR T1 - Basic and Applied Decision Making in Cancer Control AN - 57111375; 200601792 AB - Decision making is fundamental to all aspects of cancer care - prevention, detection, treatment, survivorship, and end of life - yet researchers and clinicians have limited knowledge of the ways in which patients and their health care providers make critical health decisions. Recognizing how important it is to understand how patients and their providers make potentially life-altering decisions, the National Cancer Institute developed a decision making in cancer control initiative. The goal of this initiative is to enhance understanding of human decision-making processes so that individuals can make more informed and satisfying choices regarding their health. This article describes the multidisciplinary meeting that provided the scientific foundation for this initiative. References. [Copyright 2005 The American Psychological Association.] JF - Health Psychology AU - Nelson, Wendy AU - Stefanek, Michael AU - Peters, Ellen AU - McCaul, Kevin D AD - National Cancer Instit, Bethesda, MD nelsonw@mail.nih.gov Y1 - 2005///0, PY - 2005 DA - 0, 2005 SP - S3 EP - S8 VL - 24 IS - 4 SN - 0278-6133, 0278-6133 KW - cancer KW - decision making KW - judgment and decision making KW - Interdisciplinary team work KW - Collaborative decision making KW - Doctor-Patient communication KW - Cancer KW - article UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57111375?accountid=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=Health+Psychology&rft.atitle=Basic+and+Applied+Decision+Making+in+Cancer+Control&rft.au=Nelson%2C+Wendy%3BStefanek%2C+Michael%3BPeters%2C+Ellen%3BMcCaul%2C+Kevin+D&rft.aulast=Nelson&rft.aufirst=Wendy&rft.date=2005-01-01&rft.volume=24&rft.issue=4&rft.spage=S3&rft.isbn=&rft.btitle=&rft.title=Health+Psychology&rft.issn=02786133&rft_id=info:doi/10.1037%2F0278-6133.24.4.S3 LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2006-04-07 N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Cancer; Collaborative decision making; Doctor-Patient communication; Interdisciplinary team work DO - http://dx.doi.org/10.1037/0278-6133.24.4.S3 ER - TY - JOUR T1 - A molecular phylogeny for bats illuminates biogeography and the fossil record AN - 51740885; 2005-022421 AB - Bats make up more than 20% of extant mammals, yet their evolutionary history is largely unknown because of a limited fossil record and conflicting or incomplete phylogenies. Here, we present a highly resolved molecular phylogeny for all extant bat families. Our results support the hypothesis that megabats are nested among four major microbat lineages, which originated in the early Eocene [52 to 50 million years ago (Mya)], coincident with a significant global rise in temperature, increase in plant diversity and abundance, and the zenith of Tertiary insect diversity. Our data suggest that bats originated in Laurasia, possibly in North America, and that three of the major microbat lineages are Laurasian in origin, whereas the fourth is Gondwanan. Combining principles of ghost lineage analysis with molecular divergence dates, we estimate that the bat fossil record underestimates (unrepresented basal branch length, UBBL) first occurrences by, on average, 73% and that the sum of missing fossil history is 61%. JF - Science AU - Teeling, Emma C AU - Springer, Mark S AU - Madsen, Ole AU - Bates, Paul AU - O'Brien, Stephen J AU - Murphy, William J Y1 - 2005/01// PY - 2005 DA - January 2005 SP - 580 EP - 584 PB - American Association for the Advancement of Science, Washington, DC VL - 307 IS - 5709 SN - 0036-8075, 0036-8075 KW - Chordata KW - Eocene KW - phylogeny KW - Mammalia KW - biologic evolution KW - Paleogene KW - biogeography KW - Yinpterochiroptera KW - Cenozoic KW - Yangochiroptera KW - Theria KW - Tertiary KW - Chiroptera KW - speciation KW - paleotemperature KW - Gondwana KW - extinction KW - reconstruction KW - mass extinctions KW - Vertebrata KW - fossil record KW - Eutheria KW - Tetrapoda KW - 11:Vertebrate paleontology KW - 12:Stratigraphy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/51740885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science&rft.atitle=A+molecular+phylogeny+for+bats+illuminates+biogeography+and+the+fossil+record&rft.au=Teeling%2C+Emma+C%3BSpringer%2C+Mark+S%3BMadsen%2C+Ole%3BBates%2C+Paul%3BO%27Brien%2C+Stephen+J%3BMurphy%2C+William+J&rft.aulast=Teeling&rft.aufirst=Emma&rft.date=2005-01-01&rft.volume=307&rft.issue=5709&rft.spage=580&rft.isbn=&rft.btitle=&rft.title=Science&rft.issn=00368075&rft_id=info:doi/10.1126%2Fscience.1105113 L2 - http://www.sciencemag.org/ LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 2005-01-01 N1 - Number of references - 32 N1 - PubXState - DC N1 - Document feature - illus. N1 - Last updated - 2012-06-07 N1 - CODEN - SCIEAS N1 - SubjectsTermNotLitGenreText - biogeography; biologic evolution; Cenozoic; Chiroptera; Chordata; Eocene; Eutheria; extinction; fossil record; Gondwana; Mammalia; mass extinctions; Paleogene; paleotemperature; phylogeny; reconstruction; speciation; Tertiary; Tetrapoda; Theria; Vertebrata; Yangochiroptera; Yinpterochiroptera DO - http://dx.doi.org/10.1126/science.1105113 ER - TY - JOUR T1 - A woolly mammoth (Mammuthus primigenius) nuclear DNA phylogeny AN - 51540637; 2006-074436 JF - Short Papers and Abstracts - World of Elephants Congress AU - Capelli, Cristian AU - MacPhee, Ross D E AU - Roca, Alfred L AU - Brisighelli, Francesca AU - Georgiadis, Nicholas AU - O'Brien, Stephen J AU - Greenwood, Alex D A2 - Agenbroad, Larry D. A2 - Symington, R. L. Y1 - 2005 PY - 2005 DA - 2005 SP - 34 PB - World of Elephants International Congress VL - 2 KW - experimental studies KW - Chordata KW - extinct taxa KW - living taxa KW - phylogeny KW - Mammalia KW - Proboscidea KW - biologic evolution KW - molecular biology KW - genetics KW - Elephantoidea KW - Theria KW - Mammuthus primigenius KW - DNA KW - Elephantidae KW - Africa KW - Vertebrata KW - Mammuthus KW - Eutheria KW - Tetrapoda KW - 11:Vertebrate paleontology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/51540637?accountid=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=Short+Papers+and+Abstracts+-+World+of+Elephants+Congress&rft.atitle=A+woolly+mammoth+%28Mammuthus+primigenius%29+nuclear+DNA+phylogeny&rft.au=Capelli%2C+Cristian%3BMacPhee%2C+Ross+D+E%3BRoca%2C+Alfred+L%3BBrisighelli%2C+Francesca%3BGeorgiadis%2C+Nicholas%3BO%27Brien%2C+Stephen+J%3BGreenwood%2C+Alex+D&rft.aulast=Capelli&rft.aufirst=Cristian&rft.date=2005-01-01&rft.volume=2&rft.issue=&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Short+Papers+and+Abstracts+-+World+of+Elephants+Congress&rft.issn=&rft_id=info:doi/ LA - English DB - GeoRef N1 - Conference title - 2nd world of elephants congress N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 2006-01-01 N1 - Last updated - 2012-06-07 N1 - CODEN - #06643 N1 - SubjectsTermNotLitGenreText - Africa; biologic evolution; Chordata; DNA; Elephantidae; Elephantoidea; Eutheria; experimental studies; extinct taxa; genetics; living taxa; Mammalia; Mammuthus; Mammuthus primigenius; molecular biology; phylogeny; Proboscidea; Tetrapoda; Theria; Vertebrata ER - TY - JOUR T1 - Cyto-nuclear genomic dissociation in African elephant species AN - 50275785; 2006-074477 JF - Short Papers and Abstracts - World of Elephants Congress AU - Roca, Alfred L AU - Georgiadis, Nicholas AU - O'Brien, Stephen J A2 - Agenbroad, Larry D. A2 - Symington, R. L. Y1 - 2005 PY - 2005 DA - 2005 SP - 148 PB - World of Elephants International Congress VL - 2 KW - terrestrial environment KW - dissociation KW - Elephas KW - reproduction KW - Elephantoidea KW - Theria KW - Elephantidae KW - ecology KW - Eutheria KW - forests KW - Chordata KW - living taxa KW - biochemistry KW - Mammalia KW - Proboscidea KW - molecular biology KW - genome KW - habitat KW - populations KW - DNA KW - Africa KW - savannas KW - Vertebrata KW - Tetrapoda KW - 11:Vertebrate paleontology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/50275785?accountid=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=Short+Papers+and+Abstracts+-+World+of+Elephants+Congress&rft.atitle=Cyto-nuclear+genomic+dissociation+in+African+elephant+species&rft.au=Roca%2C+Alfred+L%3BGeorgiadis%2C+Nicholas%3BO%27Brien%2C+Stephen+J&rft.aulast=Roca&rft.aufirst=Alfred&rft.date=2005-01-01&rft.volume=2&rft.issue=&rft.spage=148&rft.isbn=&rft.btitle=&rft.title=Short+Papers+and+Abstracts+-+World+of+Elephants+Congress&rft.issn=&rft_id=info:doi/ LA - English DB - GeoRef N1 - Conference title - 2nd world of elephants congress N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 2006-01-01 N1 - Number of references - 1 N1 - Last updated - 2012-06-07 N1 - CODEN - #06643 N1 - SubjectsTermNotLitGenreText - Africa; biochemistry; Chordata; dissociation; DNA; ecology; Elephantidae; Elephantoidea; Elephas; Eutheria; forests; genome; habitat; living taxa; Mammalia; molecular biology; populations; Proboscidea; reproduction; savannas; terrestrial environment; Tetrapoda; Theria; Vertebrata ER - TY - JOUR T1 - Statistics for weighing benefits and harms in a proposed genetic substudy of a randomized cancer prevention trial AN - 38197015; 2983659 AB - When evaluating potential interventions for cancer prevention, it is necessary to compare benefits and harms. With new study designs, new statistical approaches may be needed to facilitate this comparison. A case in point arose in a proposed genetic substudy of a randomized trial of tamoxifen versus placebo in asymptomatic women who were at high risk for breast cancer. Although the randomized trial showed that tamoxifen substantially reduced the risk of breast cancer, the harms from tamoxifen were serious and some were life threatening. In hopes of finding a subset of women with inherited risk genes who derive greater benefits from tamoxifen, we proposed a nested case-control study to test some trial subjects for various genes and new statistical methods to extrapolate benefits and harms to the general population. An important design question is whether or not the study should target common low penetrance genes. Our calculations show that useful results are only likely with rare high penetrance genes. Reprinted by permission of Blackwell Publishers JF - Journal of the Royal Statistical Society AU - Baker, S G AU - Kramer, B S AD - National Institutes of Health Y1 - 2005 PY - 2005 DA - 2005 SP - 941 EP - 954 VL - 54 IS - 5 SN - 0035-9254, 0035-9254 KW - Sociology KW - Risk KW - Genetics KW - Social science research KW - Data collection KW - Medical research KW - Data analysis KW - Statistical methods KW - Cancer KW - Methodology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/38197015?accountid=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=Journal+of+the+Royal+Statistical+Society&rft.atitle=Statistics+for+weighing+benefits+and+harms+in+a+proposed+genetic+substudy+of+a+randomized+cancer+prevention+trial&rft.au=Baker%2C+S+G%3BKramer%2C+B+S&rft.aulast=Baker&rft.aufirst=S&rft.date=2005-01-01&rft.volume=54&rft.issue=5&rft.spage=941&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Royal+Statistical+Society&rft.issn=00359254&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 - 11919 10902; 12228 10919; 7886 10902; 1939 3617 6220; 5460 1615 8573 11325; 7994; 3279 971 3286; 3286; 11035 ER - TY - JOUR T1 - Bayesian model selection for join point regression with application to age-adjusted cancer rates AN - 38194761; 2983658 AB - The method of Bayesian model selection for join point regression models is developed. Given a set of K + 1 join point models M0, M1,...,MK with 0, 1,..., K join points respectively, the posterior distributions of the parameters and competing models Mk are computed by Markov chain Monte Carlo simulations. The Bayes information criterion BIC is used to select the model Mk with the smallest value of BIC as the best model. Another approach based on the Bayes factor selects the model Mk with the largest posterior probability as the best model when the prior distribution of Mk is discrete uniform. Both methods are applied to analyse the observed US cancer incidence rates for some selected cancer sites. The graphs of the join point models fitted to the data are produced by using the methods proposed and compared with the method of Kim and co-workers that is based on a series of permutation tests. The analyses show that the Bayes factor is sensitive to the prior specification of the variance [sigma]2, and that the model which is selected by BIC fits the data as well as the model that is selected by the permutation test and has the advantage of producing the posterior distribution for the join points. The Bayesian join point model and model selection method that are presented here will be integrated in the National Cancer Institute's join point software (http://www.srab.cancer.gov/joinpoint/) and will be available to the public. Reprinted by permission of Blackwell Publishers JF - Journal of the Royal Statistical Society AU - Tiwari, R C AU - Cronin, K A AU - Davis, W AU - Feuer, E J AU - Yu, B. AU - Chib, S AD - National Cancer Institute ; Washington University Y1 - 2005 PY - 2005 DA - 2005 SP - 919 EP - 939 VL - 54 IS - 5 SN - 0035-9254, 0035-9254 KW - Sociology KW - Monte Carlo simulation KW - Probability KW - Social science research KW - Model testing KW - Medical research KW - Regression analysis KW - Statistical methods KW - Cancer KW - Methodology KW - Bayesian method UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/38194761?accountid=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=Journal+of+the+Royal+Statistical+Society&rft.atitle=Bayesian+model+selection+for+join+point+regression+with+application+to+age-adjusted+cancer+rates&rft.au=Tiwari%2C+R+C%3BCronin%2C+K+A%3BDavis%2C+W%3BFeuer%2C+E+J%3BYu%2C+B.%3BChib%2C+S&rft.aulast=Tiwari&rft.aufirst=R&rft.date=2005-01-01&rft.volume=54&rft.issue=5&rft.spage=919&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Royal+Statistical+Society&rft.issn=00359254&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 - 11919 10902; 12228 10919; 7886 10902; 1939 3617 6220; 10739 12228 10919; 1512 3865 4025; 7994; 8268 12265 3865 4025 10214 12224 971 12228 10919; 8160 8163; 10214 12224 971 ER - TY - JOUR T1 - Resolving paradoxes involving surrogate end points AN - 38192738; 2980086 AB - We define a surrogate end point as a measure or indicator of a biological process that is obtained sooner, at less cost or less invasively than a true end point of health outcome and is used to make conclusions about the effect of an intervention on the true end point. Prentice presented criteria for valid hypothesis testing of a surrogate end point that replaces a true end point. For using the surrogate end point to estimate the predicted effect of intervention on the true end point, Day and Duffy assumed the Prentice criterion and arrived at two paradoxical results: the estimated predicted intervention effect by using a surrogate can give more precise estimates than the usual estimate of the intervention effect by using the true end point and the variance is greatest when the surrogate end point perfectly predicts the true end point. Begg and Leung formulated similar paradoxes and concluded that they indicate a flawed conceptual strategy arising from the Prentice criterion. We resolve the paradoxes as follows. Day and Duffy compared a surrogate-based estimate of the effect of intervention on the true end point with an estimate of the effect of intervention on the true end point that uses the true end point. Their paradox arose because the former estimate assumes the Prentice criterion whereas the latter does not. If both or neither of these estimates assume the Prentice criterion, there is no paradox. The paradoxes of Begg and Leung, although similar to those of Day and Duffy, arise from ignoring the variability of the parameter estimates irrespective of the Prentice criterion and disappear when the variability is included. Our resolution of the paradoxes provides a firm foundation for future meta-analytic extensions of the approach of Day and Duffy. Reprinted by permission of Blackwell Publishers JF - Journal of the Royal Statistical Society AU - Baker, S G AU - Izmirlian, G AU - Kipnis, V AD - National Cancer Institute Y1 - 2005 PY - 2005 DA - 2005 SP - 753 EP - 762 VL - 168 IS - 4 SN - 0964-1998, 0964-1998 KW - Sociology KW - Measurement KW - Medical sociology KW - Statistical models KW - Statistical analysis KW - Patients KW - Health KW - Data analysis KW - Statistical methods KW - Methodology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/38192738?accountid=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=Journal+of+the+Royal+Statistical+Society&rft.atitle=Resolving+paradoxes+involving+surrogate+end+points&rft.au=Baker%2C+S+G%3BIzmirlian%2C+G%3BKipnis%2C+V&rft.aulast=Baker&rft.aufirst=S&rft.date=2005-01-01&rft.volume=168&rft.issue=4&rft.spage=753&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+Royal+Statistical+Society&rft.issn=09641998&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 - 12228 10919; 7887 12008; 12224 971; 3279 971 3286; 5772; 9271 7890 5792 10484; 7854; 7994; 12230 8163 ER - TY - JOUR T1 - The CIS model for collaborative research in health communications: a brief retrospective from the current generation of research AN - 37759173; 3283940 AB - The Cancer Information Service (CIS) of the National Cancer Institute (NCI) is the premiere organization for providing cancer information to the nation. The CIS provides a stellar example of how a service organization dedicated to health communications also can serve as a laboratory for research. This journey by the CIS into health communication research is described briefly, along with the current generation of research summarized in this issue of the Journal of Health Communication (JHC). The CIS model for collaborative research is presented as an exemplar that other service organizations might embrace as a strategic tool for quality improvement in health communications. Reprinted by permission of Taylor & Francis Ltd. JF - Journal of health communication AU - Marcus, Alfred C AU - Morra, Marion E AU - Bright, Mary Anne AU - Fleisher, Linda AU - Kreps, Gary AU - Perocchia, Rosemarie AD - AMC Cancer Research Center ; Morra Communications ; National Cancer Institute ; Fox Chase Cancer Center ; George Mason University Y1 - 2005 PY - 2005 DA - 2005 SP - 235 EP - 245 VL - 10 IS - Suppl SN - 1081-0730, 1081-0730 KW - Sociology KW - Information services KW - Quality of service KW - Medical research KW - Health education KW - Communication KW - Medical treatment KW - U.S.A. KW - Cancer KW - Information exchange UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/37759173?accountid=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=Journal+of+health+communication&rft.atitle=The+CIS+model+for+collaborative+research+in+health+communications%3A+a+brief+retrospective+from+the+current+generation+of+research&rft.au=Marcus%2C+Alfred+C%3BMorra%2C+Marion+E%3BBright%2C+Mary+Anne%3BFleisher%2C+Linda%3BKreps%2C+Gary%3BPerocchia%2C+Rosemarie&rft.aulast=Marcus&rft.aufirst=Alfred&rft.date=2005-01-01&rft.volume=10&rft.issue=Suppl&rft.spage=235&rft.isbn=&rft.btitle=&rft.title=Journal+of+health+communication&rft.issn=10810730&rft_id=info:doi/10.1080%2F10810730500263612 LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 5779 4049; 7886 10902; 6532 6515; 1939 3617 6220; 6522 4577 3872 554 971; 7890 5792 10484; 2572; 10526; 433 293 14 DO - http://dx.doi.org/10.1080/10810730500263612 ER - TY - JOUR T1 - A case study in dissemination: lessons learned from a pilot study involving the national cancer institute's cancer information service AN - 37759126; 3283939 AB - The Cancer Information Service Research Consortium (CISRC) was funded by the National Cancer Institute to disseminate as a pilot study a longitudinally tailored print intervention to promote the 5 A Day for Better Health program among callers to the National Cancer Institute's Cancer Information Service (CIS). Using a one-group (intervention-only) study design, 1,022 eligible CIS callers were enrolled to receive the intervention consisting of four mailings of tailored print materials over a 3-month period. Program evaluation focused on process and implementation evaluation, including adherence to the baseline interviews by CIS information specialists based on live-call monitoring (n = 55 eligible callers), and the timeliness of the intervention mailouts (4,088 scheduled mailouts). Adherence to the baseline interviews by CIS information specialists was extremely high, exceeding 90% for all indicators of quality control. Of the 4,088 intervention mailings, 75% occurred on or before the target date, while 95% occurred within 21 days of the target date. All delays in the scheduled mailouts occurred in the first mailing, due to changes made in the production process (batch printing of all tailored print materials at baseline). This change required additional system upgrades and more intensive and time-consuming quality control than originally anticipated, which was exacerbated by the faster-than-expected accrual of eligible participants. Based on this pilot study, the CIS is now positioned for widespread dissemination of the 5 A Day tailored print intervention. Several key lessons learned are also identified to facilitate the transition from research to dissemination. Reprinted by permission of Taylor & Francis Ltd. JF - Journal of health communication AU - Marcus, Alfred C AU - Heimendinger, Jerianne AU - Berman, Ellen AU - Strecher, Victor AU - Bright, Mary Anne AU - Allen, Amy Reasinger AU - Davis, Sharon W AU - Julesberg, Karen AU - Mowad, Linda Z AU - Nguyen, Lynne H AU - Perocchia, Rosemarie AU - Thomsen, Chris AD - AMC Cancer Research Center ; Aspen Systems Corporation ; University of Michigan ; National Cancer Institute ; West Virginia University ; Northern California Cancer Center ; University of Wisconsin ; Yale University ; M.D. Anderson Cancer Center ; Memorial Sloan-Kettering Cancer Center Y1 - 2005 PY - 2005 DA - 2005 SP - 219 EP - 234 VL - 10 IS - Suppl SN - 1081-0730, 1081-0730 KW - Sociology KW - Case studies KW - Health care KW - Information services KW - Health education KW - Medical research KW - Health policy KW - Medical treatment KW - Policy implementation KW - Interviews KW - U.S.A. UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/37759126?accountid=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=Journal+of+health+communication&rft.atitle=A+case+study+in+dissemination%3A+lessons+learned+from+a+pilot+study+involving+the+national+cancer+institute%27s+cancer+information+service&rft.au=Marcus%2C+Alfred+C%3BHeimendinger%2C+Jerianne%3BBerman%2C+Ellen%3BStrecher%2C+Victor%3BBright%2C+Mary+Anne%3BAllen%2C+Amy+Reasinger%3BDavis%2C+Sharon+W%3BJulesberg%2C+Karen%3BMowad%2C+Linda+Z%3BNguyen%2C+Lynne+H%3BPerocchia%2C+Rosemarie%3BThomsen%2C+Chris&rft.aulast=Marcus&rft.aufirst=Alfred&rft.date=2005-01-01&rft.volume=10&rft.issue=Suppl&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Journal+of+health+communication&rft.issn=10810730&rft_id=info:doi/10.1080%2F10810730500257689 LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 2056 10902; 6532 6515; 7886 10902; 5779 4049; 7890 5792 10484; 6832 10919; 9624 9625 9628; 5788 11888 10472; 5775 13521; 433 293 14 DO - http://dx.doi.org/10.1080/10810730500257689 ER - TY - JOUR T1 - Use and impact of ehealth system by low-income women with breast cancer AN - 37758433; 3283938 AB - This article is the second of a two-part series reporting on a population-based study intended to use an eHealth system to examine the feasibility of reaching underserved women with breast cancer (Gustafson, McTavish et al., Reducing the digital divide for low-income women with breast cancer, 2004; Madison Center for Health Systems Research and Analysis, University of Wisconsin; Comprehensive Health Enhancement Support System [CHESS]) and determine how they use the system and what impact it had on them. Participants included women recently diagnosed with breast cancer whose income was at or below 250% of poverty level and were living in rural Wisconsin (n = 144; all Caucasian) or Detroit (n = 85; all African American). Because this was a population-based study all 229 participants received CHESS. A comparison group of patients (n = 51) with similar demographics was drawn from a separate recently completed randomized clinical trial. Use rates (e.g., frequency and length of use as well as type of use) as well as impact on several dimensions of quality of life and participation in health care are reported. Low-income subjects in this study logged on and spent more time on CHESS than more affluent women in a previous study. Urban African Americans used information and analysis services more and communication services less than rural Caucasians. When all low-income women from this study are combined and compared with a low-income control group from another study, the CHESS group was superior to that control group in 4 of 8 outcome variables at both statistically and practically significant levels (social support, negative emotions, participation in health care, and information competence). When African Americans and Caucasians are separated the control group's sample size becomes 30 and 21 thus reducing power. Statistical significance is retained, however, in all four outcomes for Caucasians Reprinted by permission of Taylor & Francis Ltd. JF - Journal of health communication AU - Gustafson, David H AU - McTavish, Fiona M AU - Stengle, William AU - Ballard, Denise AU - Hawkins, Robert AU - Shaw, Bret R AU - Jones, Ellen AU - Julèsberg, Karen AU - McDowell, Helene AU - Chen, Wei Chih AU - Volrathongchai, Kanittha AU - Landucci, Gina AD - University of Wisconsin ; National Cancer Institute ; University of Wisconsin-Madison Y1 - 2005 PY - 2005 DA - 2005 SP - 195 EP - 218 VL - 10 IS - Suppl SN - 1081-0730, 1081-0730 KW - Sociology KW - Breast cancer KW - Demography KW - New technology KW - Information services KW - Health care KW - Ethnicity KW - U.S.A. KW - Low income KW - Cancer KW - Urban areas KW - Quality of life KW - Communications technology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/37758433?accountid=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=Journal+of+health+communication&rft.atitle=Use+and+impact+of+ehealth+system+by+low-income+women+with+breast+cancer&rft.au=Gustafson%2C+David+H%3BMcTavish%2C+Fiona+M%3BStengle%2C+William%3BBallard%2C+Denise%3BHawkins%2C+Robert%3BShaw%2C+Bret+R%3BJones%2C+Ellen%3BJul%C3%A8sberg%2C+Karen%3BMcDowell%2C+Helene%3BChen%2C+Wei+Chih%3BVolrathongchai%2C+Kanittha%3BLanducci%2C+Gina&rft.aulast=Gustafson&rft.aufirst=David&rft.date=2005-01-01&rft.volume=10&rft.issue=Suppl&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Journal+of+health+communication&rft.issn=10810730&rft_id=info:doi/10.1080%2F10810730500263257 LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 5775 13521; 8662 12622; 2592 12622; 6532 6515; 1939 3617 6220; 7553 6271; 3412; 10525 12162 3898; 4435; 13161 1247; 433 293 14 DO - http://dx.doi.org/10.1080/10810730500263257 ER - TY - JOUR T1 - The national cancer institute's cancer information service: a new generation of service and research to the nation AN - 37758399; 3283927 AB - The national Cancer Institute (NCI), the nation's leading agency for cancer information and research, mandated by the U.S. Congress to provide accurate, up-to-date information about cancer to all segments of the U.S. population, established the Cancer Information Service (CIS) on July 1, 1975. Using a two-pronged approach, the telephone information service and education programs for the public and health professionals, the CIS was designed to maximize its reach. In 1982, the CIS implemented three tools: the Call Record Form to record data about each call to the service, a national user survey, and a system of national test calls. These resulted in a rich data source and an infrastructure that allowed collaborative health communications research with the CIS to emerge later in the decade. As the CIS embarks on a new generation of service to the nation, it is now characterized by three vital components that advance the NCI's overall mission of cancer prevention and control: a Partnership Program, Multichannel Contact Centers, and a Health Communications Research Program. Reprinted by permission of Taylor & Francis Ltd. JF - Journal of health communication AU - Bright, Mary Anne AD - National Cancer Institute Y1 - 2005 PY - 2005 DA - 2005 SP - 7 EP - 14 VL - 10 IS - Suppl SN - 1081-0730, 1081-0730 KW - Sociology KW - Health care KW - Information services KW - Public interest KW - Medical research KW - Medical treatment KW - U.S.A. KW - Data analysis KW - Cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/37758399?accountid=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=Journal+of+health+communication&rft.atitle=The+national+cancer+institute%27s+cancer+information+service%3A+a+new+generation+of+service+and+research+to+the+nation&rft.au=Bright%2C+Mary+Anne&rft.aulast=Bright&rft.aufirst=Mary&rft.date=2005-01-01&rft.volume=10&rft.issue=Suppl&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Journal+of+health+communication&rft.issn=10810730&rft_id=info:doi/10.1080%2F10810730500263687 LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 1939 3617 6220; 7886 10902; 7890 5792 10484; 10454; 6532 6515; 3279 971 3286; 5775 13521; 433 293 14 DO - http://dx.doi.org/10.1080/10810730500263687 ER - TY - JOUR T1 - Exploring e-health usage and interest among cancer information service users: the need for personalized interactions and multiple channels remains AN - 37756430; 3283929 AB - Since searching for health information is among the most popular uses of the Internet, we analyzed a survey of 6,019 callers to the National Cancer Institute's (NCI's) Cancer Information Service (CIS) to assess Internet usage and interest in technologies to access health and cancer information. Findings suggest that about 40% of CIS callers used the Internet to obtain cancer information and, of these, only about 20% found all the information they sought. Nearly 33% of Internet users called the CIS to discuss information found on the Internet; most (>90%) reported that the CIS was helpful. Those who sought cancer information on the Internet were more likely to call the CIS about this information if they found all or most of the information they were seeking, compared with those who found some or little of the information. New communication services endorsed by most CIS callers included e-mails from an information specialist and telephone support from the CIS while on the Internet. The survey results indicate the importance of multiple access points, both traditional and technology based, and that there is still a need for more traditional, personalized forms of health communication. A crucial question is how best to harness and integrate these new technologies within the current generation of mediated health information systems. Reprinted by permission of Taylor & Francis Ltd. JF - Journal of health communication AU - Bright, Mary Anne AU - Fleisher, Linda AU - Thomsen, Chris AU - Morra, Marion E AU - Marcus, Al AU - Gehring, Wendy AD - National Cancer Institute ; Fox Chase Cancer Center ; National Institutes of Health ; Morra Communications ; University of Colorado ; Cooper Institute Denver Y1 - 2005 PY - 2005 DA - 2005 SP - 35 EP - 52 VL - 10 IS - Suppl SN - 1081-0730, 1081-0730 KW - Sociology KW - New technology KW - Telephone KW - Information services KW - Surveys KW - Health KW - U.S.A. KW - Data analysis KW - Internet KW - Communications technology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/37756430?accountid=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=Journal+of+health+communication&rft.atitle=Exploring+e-health+usage+and+interest+among+cancer+information+service+users%3A+the+need+for+personalized+interactions+and+multiple+channels+remains&rft.au=Bright%2C+Mary+Anne%3BFleisher%2C+Linda%3BThomsen%2C+Chris%3BMorra%2C+Marion+E%3BMarcus%2C+Al%3BGehring%2C+Wendy&rft.aulast=Bright&rft.aufirst=Mary&rft.date=2005-01-01&rft.volume=10&rft.issue=Suppl&rft.spage=35&rft.isbn=&rft.btitle=&rft.title=Journal+of+health+communication&rft.issn=10810730&rft_id=info:doi/10.1080%2F10810730500265609 LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 6532 6515; 6813 6518; 2592 12622; 12429; 3279 971 3286; 8662 12622; 12647 12641 2572; 5772; 433 293 14 DO - http://dx.doi.org/10.1080/10810730500265609 ER - TY - JOUR T1 - Cancer patients' information needs across the cancer care continuum: evidence from the cancer information service AN - 37756387; 3283928 AB - This study examines the information needs of cancer patients who contacted the National Cancer Institute's (NCI's) Cancer Information Service (CIS) via a toll-free telephone number. Records from 19,030 calls received from cancer patients between September 2002 and August 2003 were analyzed to determine differences in subjects of interaction (main topics of inquiry and discussion) for subgroups of patients based on demographic characteristics and stage along the cancer care continuum (pretreatment, in-treatment, post-treatment, recurrence). Females were more likely than males to inquire about cancer screening/diagnosis, support services, psychosocial issues, and general cancer site information, but they were less likely to seek specific cancer treatment information. Older patients were more likely than younger patients to seek specific treatment information, but they were less interested in support services, psychosocial issues, and prevention/risk factors. Compared with White callers, Hispanics and most minorities were more likely to seek support service information, and African Americans were more likely to have questions related to psychosocial issues. Compared with patients in treatment, patients in recurrence were more likely to seek specific treatment information; patients not in treatment were more likely to seek medical referral information; and patients in post-treatment were more likely to seek screening/diagnosis and prevention/risk risk factor information. Findings will help the CIS and other cancer-focused organizations address the distinct information needs of different subsets of cancer patients. Reprinted by permission of Taylor & Francis Ltd. JF - Journal of health communication AU - Squiers, Linda AU - Rutten, Lila J. Finney AU - Treiman, Katherine AU - Bright, Mary Anne AU - Hesse, Bradford AD - National Cancer Institute Y1 - 2005 PY - 2005 DA - 2005 SP - 15 EP - 34 VL - 10 IS - Suppl SN - 1081-0730, 1081-0730 KW - Sociology KW - Age KW - Health care KW - Information services KW - Ethnicity KW - Psychology KW - Social problems KW - Gender differentiation KW - Medical treatment KW - Patients KW - U.S.A. KW - Cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/37756387?accountid=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=Journal+of+health+communication&rft.atitle=Cancer+patients%27+information+needs+across+the+cancer+care+continuum%3A+evidence+from+the+cancer+information+service&rft.au=Squiers%2C+Linda%3BRutten%2C+Lila+J.+Finney%3BTreiman%2C+Katherine%3BBright%2C+Mary+Anne%3BHesse%2C+Bradford&rft.aulast=Squiers&rft.aufirst=Linda&rft.date=2005-01-01&rft.volume=10&rft.issue=Suppl&rft.spage=15&rft.isbn=&rft.btitle=&rft.title=Journal+of+health+communication&rft.issn=10810730&rft_id=info:doi/10.1080%2F10810730500263620 LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 1939 3617 6220; 9271 7890 5792 10484; 6532 6515; 7890 5792 10484; 5423 3549 2688 2449 10404; 646; 10404; 11893 11979; 4435; 5775 13521; 433 293 14 DO - http://dx.doi.org/10.1080/10810730500263620 ER - TY - JOUR T1 - Reducing the digital divide for low-income women with breast cancer: a feasibility study of a population-based intervention AN - 37755890; 3283937 AB - A fundamental challenge to helping underserved women and their families cope with breast cancer is providing them with easily accessible, reliable health care information and support. This is specially true for low-income families living in rural areas where resources are few and frequently distant as well as low-income families in urban areas where access to information and support can be complex and overwhelming. The Internet is one mechanism that has tremendous potential to help these families cope with breast cancer. This article describes a feasibility test of the potential for the National Cancer Institute's (NCI's) Cancer Information Service (CIS) to provide access to an Internet-based system that has been shown to improve quality of life for underserved breast cancer patients. The test was conducted in rural Wisconsin (low socioeconomic status [SES] Caucasian women) and in Detroit, Michigan (low SES African American women), and compares the effectiveness of several different dissemination strategies. Using these results we propose a model for how CIS telephone and partnership program services could efficiently disseminate such information and support systems. In doing so we believe that important steps can be taken to close the digital divide that separates low-income families from the resources they need to effectively face cancer. This is the first of two articles coming from this study. A companion article reports on an evaluation of the use and impact of this system on the women who were given access to it. Reprinted by permission of Taylor & Francis Ltd. JF - Journal of health communication AU - Gustafson, David H AU - McTavish, Fiona M AU - Stengle, William AU - Ballard, Denise AU - Jones, Ellen AU - Julesberg, Karen AU - McDowell, Helene AU - Landucci, Gina AU - Hawkins, Robert AD - University of Wisconsin ; National Cancer Institute Y1 - 2005 PY - 2005 DA - 2005 SP - 173 EP - 194 VL - 10 IS - Suppl SN - 1081-0730, 1081-0730 KW - Sociology KW - Breast cancer KW - Digital technology KW - Health care KW - Information services KW - Women KW - Medical treatment KW - U.S.A. KW - Family relations KW - Internet KW - Low income KW - Cancer UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/37755890?accountid=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=Journal+of+health+communication&rft.atitle=Reducing+the+digital+divide+for+low-income+women+with+breast+cancer%3A+a+feasibility+study+of+a+population-based+intervention&rft.au=Gustafson%2C+David+H%3BMcTavish%2C+Fiona+M%3BStengle%2C+William%3BBallard%2C+Denise%3BJones%2C+Ellen%3BJulesberg%2C+Karen%3BMcDowell%2C+Helene%3BLanducci%2C+Gina%3BHawkins%2C+Robert&rft.aulast=Gustafson&rft.aufirst=David&rft.date=2005-01-01&rft.volume=10&rft.issue=Suppl&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Journal+of+health+communication&rft.issn=10810730&rft_id=info:doi/10.1080%2F10810730500263281 LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 13598 5421 6091; 1939 3617 6220; 7553 6271; 3557 12622; 6813 6518; 4777 6093; 7890 5792 10484; 6532 6515; 5775 13521; 433 293 14 DO - http://dx.doi.org/10.1080/10810730500263281 ER - TY - JOUR T1 - Quality of life in HIV-infected individuals receiving antiretroviral therapy is related to adherence AN - 36687918; 3436142 AB - This study assesses changes in quality of life (QoL) over time among HIV-infected individuals receiving antiretroviral therapy (ART) and evaluates how this relates to ART adherence. Prospective, longitudinal data were examined from 1050 participants in two large, randomized, multi-centre antiretroviral clinical trials. QoL was assessed by the SF-12; adherence by the Terry Beirn Community Programs for Clinical Research on AIDS Antiretroviral Medication Self-report. Participants included 20% women, 53% African Americans, 16% Latinos; mean age was 39 years; mean baseline CD4 + cell count 230 cels/mm3; 89% were ART-naïve at entry. Baseline physical and mental health summary QoL scores were 45.4 and 42.9, comparable to scores reported in other advanced HIV populations. Significant improvements in mean QoL scores were seen for the group as a whole after 1 to 4 months on new ART regimens, and persisted for 12 months. Participants reporting 100% ART adherence achieved significantly higher QoL scores at 12 months compared to those with poorer adherence, particularly if 100% adherence was consistent (p <0.001). Those with at least 80% ART adherence had smaller gains in QoL at 12 months when compared to baseline, while those with <80% adherence had worsening of QoL. In this analysis, ART adherence was associated with improved QoL, particularly if adherence was sustained. Reprinted by permission of Routledge, Taylor & Francis Ltd. JF - AIDS care AU - Mannheimer, S B AU - Matts, J AU - Telzak, E AU - Chesney, M AU - Child, C AU - Wu, A W AU - Friedland, G AD - Columbia University ; University of Minnesota ; Albert Einstein College of Medicine ; National Institutes of Health ; University of California, San Francisco ; Johns Hopkins University ; Yale University Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 10 EP - 22 VL - 17 IS - 1 SN - 0954-0121, 0954-0121 KW - Sociology KW - Qualitative analysis KW - Longitudinal studies KW - AIDS KW - Mental health KW - Medical treatment KW - HIV KW - Quality of life UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/36687918?accountid=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=AIDS+care&rft.atitle=Quality+of+life+in+HIV-infected+individuals+receiving+antiretroviral+therapy+is+related+to+adherence&rft.au=Mannheimer%2C+S+B%3BMatts%2C+J%3BTelzak%2C+E%3BChesney%2C+M%3BChild%2C+C%3BWu%2C+A+W%3BFriedland%2C+G&rft.aulast=Mannheimer&rft.aufirst=S&rft.date=2005-01-01&rft.volume=17&rft.issue=1&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=AIDS+care&rft.issn=09540121&rft_id=info:doi/10.1080%2F09540120412331305098 LA - English DB - International Bibliography of the Social Sciences (IBSS) N1 - Date revised - 2013-06-12 N1 - Last updated - 2013-09-16 N1 - SubjectsTermNotLitGenreText - 7541 7537 971; 5703 3617 6220; 482 3617 6220; 10525 12162 3898; 7890 5792 10484; 7947 5772 7954; 10519 3279 971 3286 DO - http://dx.doi.org/10.1080/09540120412331305098 ER - TY - JOUR T1 - SLIM: an alternative Web interface for MEDLINE/PubMed searches - a preliminary study AN - 21240366; 7679391 AB - Background With the rapid growth of medical information and the pervasiveness of the Internet, online search and retrieval systems have become indispensable tools in medicine. The progress of Web technologies can provide expert searching capabilities to non-expert information seekers. The objective of the project is to create an alternative search interface for MEDLINE/PubMed searches using JavaScript slider bars. SLIM, or Slider Interface for MEDLINE/PubMed searches, was developed with PHP and JavaScript. Interactive slider bars in the search form controlled search parameters such as limits, filters and MeSH terminologies. Connections to PubMed were done using the Entrez Programming Utilities (E-Utilities). Custom scripts were created to mimic the automatic term mapping process of Entrez. Page generation times for both local and remote connections were recorded. Results Alpha testing by developers showed SLIM to be functionally stable. Page generation times to simulate loading times were recorded the first week of alpha and beta testing. Average page generation times for the index page, previews and searches were 2.94 milliseconds, 0.63 seconds and 3.84 seconds, respectively. Eighteen physicians from the US, Australia and the Philippines participated in the beta testing and provided feedback through an online survey. Most users found the search interface user-friendly and easy to use. Information on MeSH terms and the ability to instantly hide and display abstracts were identified as distinctive features. Conclusion SLIM can be an interactive time-saving tool for online medical literature research that improves user control and capability to instantly refine and refocus search strategies. With continued development and by integrating search limits, methodology filters, MeSH terms and levels of evidence, SLIM may be useful in the practice of evidence-based medicine. JF - BMC Medical Informatics and Decision Making AU - Muin, Michael AU - Fontelo, Paul AU - Liu, Fang AU - Ackerman, Michael AD - 1 Office of High Performance Computing and Communications, National Library of Medicine, 8600 Rockville Pike, Bethesda, Maryland 20894, USA, mmuin@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 37 PB - BioMed Central Ltd., Middlesex House VL - 5 KW - Biotechnology and Bioengineering Abstracts KW - Filters KW - Decision making KW - Informatics KW - Feedback KW - Mapping KW - Internet KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21240366?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Medical+Informatics+and+Decision+Making&rft.atitle=SLIM%3A+an+alternative+Web+interface+for+MEDLINE%2FPubMed+searches+-+a+preliminary+study&rft.au=Muin%2C+Michael%3BFontelo%2C+Paul%3BLiu%2C+Fang%3BAckerman%2C+Michael&rft.aulast=Muin&rft.aufirst=Michael&rft.date=2005-01-01&rft.volume=5&rft.issue=&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=BMC+Medical+Informatics+and+Decision+Making&rft.issn=1472-6947&rft_id=info:doi/10.1186%2F1472-6947-5-37 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Filters; Mapping; Feedback; Internet; Informatics; Decision making DO - http://dx.doi.org/10.1186/1472-6947-5-37 ER - TY - JOUR T1 - Current practices in cancer spatial data analysis: a call for guidance AN - 21233684; 7249901 AB - There has long been a recognition that place matters in health, from recognition of clusters of yellow fever and cholera in the 1800s to modern day analyses of regional and neighborhood effects on cancer patterns. Here we provide a summary of discussions about current practices in the spatial analysis of georeferenced cancer data by a panel of experts recently convened at the National Cancer Institute. JF - International Journal of Health Geographics AU - Pickle, Linda Williams AU - Waller, Lance A AU - Lawson, Andrew B AD - Division of Cancer Control and Population Sciences, National Cancer Institute, 6116 Executive Blvd., Suite 504, Bethesda, MD 20892, USA, picklel@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 4 SN - 1476-072X, 1476-072X KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - Article No. 3 KW - Data processing KW - Yellow fever KW - Cholera KW - Cancer KW - V 22490:Miscellaneous KW - J 02490:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21233684?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Health+Geographics&rft.atitle=Current+practices+in+cancer+spatial+data+analysis%3A+a+call+for+guidance&rft.au=Pickle%2C+Linda+Williams%3BWaller%2C+Lance+A%3BLawson%2C+Andrew+B&rft.aulast=Pickle&rft.aufirst=Linda&rft.date=2005-01-01&rft.volume=4&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Health+Geographics&rft.issn=1476072X&rft_id=info:doi/10.1186%2F1476-072X-4-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-02-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Data processing; Yellow fever; Cholera; Cancer DO - http://dx.doi.org/10.1186/1476-072X-4-3 ER - TY - JOUR T1 - HIV Vaccine DEVELOPMENT AN - 21220123; 11188814 AB - For the past two decades, scientists have aggressively pursued the development of a vaccine against human immunodeficiency virus (HIV). The magnitude of this effort is unprecedented in the history of infectious diseases. However, difficulties in finding promising candidate vaccines have limited the number of clinical efficacy trials. The macaque model is well suited for the evaluation of potential vaccines, but comparison of results among studies is often complicated by the use of different macaque species and/or challenge viruses. This review discusses current results obtained in the macaque model and human vaccine trials. JF - Frontiers in Bioscience AU - Singh, M AU - Jeang, K-T AU - Smith, S M AD - Molecular Virology Section, Laboratory of Molecular Medicine, NIAID, NIH, Bethesda, Maryland, USA Y1 - 2005 PY - 2005 DA - 2005 SP - 2064 EP - 2031 VL - 10 SN - 1093-9946, 1093-9946 KW - Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts KW - Infectious diseases KW - Human immunodeficiency virus KW - Macaca KW - Reviews KW - Vaccines KW - Clinical trials KW - Models KW - V 22360:AIDS and HIV KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21220123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Frontiers+in+Bioscience&rft.atitle=HIV+Vaccine+DEVELOPMENT&rft.au=Singh%2C+M%3BJeang%2C+K-T%3BSmith%2C+S+M&rft.aulast=Singh&rft.aufirst=M&rft.date=2005-01-01&rft.volume=10&rft.issue=&rft.spage=2064&rft.isbn=&rft.btitle=&rft.title=Frontiers+in+Bioscience&rft.issn=10939946&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Infectious diseases; Reviews; Vaccines; Clinical trials; Models; Human immunodeficiency virus; Macaca ER - TY - JOUR T1 - Complexities in Understanding the Nature of the Dose-Response for Dioxins and Related Compounds AN - 21115080; 11327635 JF - Dose-Response AU - Walker, N J AU - Yang, J-H AD - National Institute of Environmental Health Sciences, P.O. Box 12233. MD EC-34, 111 T.W. Alexander Dr., Research Triangle Park. NC 27709, USA, walker3@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 267 EP - 272 VL - 3 IS - 3 SN - 1559-3258, 1559-3258 KW - Toxicology Abstracts KW - Dioxin KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21115080?accountid=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=Dose-Response&rft.atitle=Complexities+in+Understanding+the+Nature+of+the+Dose-Response+for+Dioxins+and+Related+Compounds&rft.au=Walker%2C+N+J%3BYang%2C+J-H&rft.aulast=Walker&rft.aufirst=N&rft.date=2005-01-01&rft.volume=3&rft.issue=3&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Dose-Response&rft.issn=15593258&rft_id=info:doi/10.2203%2Fdose-response.003.03.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-12-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Dioxin DO - http://dx.doi.org/10.2203/dose-response.003.03.001 ER - TY - JOUR T1 - Analysis of Nonlinear Regression Models: A Cautionary Note AN - 21114049; 11327640 AB - Regression models are routinely used in many applied sciences for describing the relationship between a response variable and an independent variable. Statistical inferences on the regression parameters are often performed using the maximum likelihood estimators (MLE). In the case of nonlinear models the standard errors of MLE are often obtained by linearizing the nonlinear function around the true parameter and by appealing to large sample theory. In this article we demonstrate, through computer simulations, that the resulting asymptotic Wald confidence intervals cannot be trusted to achieve the desired confidence levels. Sometimes they could underestimate the true nominal level and are thus liberal. Hence one needs to be cautious in using the usual linearized standard errors of MLE and the associated confidence intervals. JF - Dose-Response AU - Peddada, S D AU - Haseman, J K AD - Biostatistics Branch, National institute of Environmental Health Sciences (NIH), Research Triangle Park, NC 27709, USA, peddada@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 342 EP - 352 VL - 3 IS - 3 SN - 1559-3258, 1559-3258 KW - Toxicology Abstracts KW - Mathematical models KW - Statistics KW - Regression analysis KW - Models KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21114049?accountid=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=Dose-Response&rft.atitle=Analysis+of+Nonlinear+Regression+Models%3A+A+Cautionary+Note&rft.au=Peddada%2C+S+D%3BHaseman%2C+J+K&rft.aulast=Peddada&rft.aufirst=S&rft.date=2005-01-01&rft.volume=3&rft.issue=3&rft.spage=342&rft.isbn=&rft.btitle=&rft.title=Dose-Response&rft.issn=15593258&rft_id=info:doi/10.2203%2Fdose-response.003.03.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-12-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Statistics; Mathematical models; Regression analysis; Models DO - http://dx.doi.org/10.2203/dose-response.003.03.005 ER - TY - JOUR T1 - Center for the Evaluation of Risks to Human Reproduction-The First Five Years AN - 21033402; 6152605 AB - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR) was established by the NTP and the National Institute of Environmental Health Sciences (NIEHS) in 1998 to address the impact of chemical exposures on human reproductive and developmental health and to serve as an environmental and reproductive health resource for government agencies and the general public. The purpose of this report is to provide an overview of the Center activities and a summary of NTP conclusions on chemicals evaluated during this time period. CERHR evaluations involve the critical review of reproductive, developmental, and other relevant toxicity data by independent panels of scientists. The products of these evaluations are expert panel reports. The public has opportunities to provide oral comments at the panel meeting and written comments on draft and final expert panel reports. The NTP evaluates these comments, the conclusions of the expert panel, and any new data not available at the time of the panel meeting, and prepares an NTP brief that describes in plain language the NTP's conclusions on the reproductive and developmental hazard from specified chemical exposures. The NTP brief, expert panel report, and public comments comprise the NTP monograph on the chemical. Monographs are sent to federal regulatory agencies, the NTP Executive Committee, and the NTP Board of Scientific Counselors, and are publicly available. Over the last five years, CERHR conducted expert panel evaluations on 14 chemicals. At this time, 13 panel reports have been published and 12 NTP-CERHR monographs have been issued. Additionally, CERHR conducted a 2-day workshop on the role of thyroid hormones in reproductive and developmental health. JF - Birth Defects Research Part B: Developmental and Reproductive Toxicology AU - Jahnke, Gloria D AU - Iannucci, Annette R AU - Scialli, Anthony R AU - Shelby, Michael D AD - Sciences International, Inc. Research Triangle Park, North Carolina, Jahnke@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 1 EP - 8 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 74 IS - 1 SN - 1542-9733, 1542-9733 KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - reproduction KW - fertility KW - development KW - birth defects KW - panel review KW - Data processing KW - Conferences KW - Sensory evaluation KW - Thyroid KW - Environmental health KW - committees KW - Toxicity KW - Hormones KW - Thyroid hormones KW - Reviews KW - Congenital defects KW - plains KW - Language KW - Reproduction KW - Toxicology KW - Government agencies KW - H 12000:Epidemiology and Public Health KW - X 24350:Industrial Chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21033402?accountid=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=Birth+Defects+Research+Part+B%3A+Developmental+and+Reproductive+Toxicology&rft.atitle=Center+for+the+Evaluation+of+Risks+to+Human+Reproduction-The+First+Five+Years&rft.au=Jahnke%2C+Gloria+D%3BIannucci%2C+Annette+R%3BScialli%2C+Anthony+R%3BShelby%2C+Michael+D&rft.aulast=Jahnke&rft.aufirst=Gloria&rft.date=2005-01-01&rft.volume=74&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Birth+Defects+Research+Part+B%3A+Developmental+and+Reproductive+Toxicology&rft.issn=15429733&rft_id=info:doi/10.1002%2Fbdrb.20028 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Thyroid hormones; Data processing; Conferences; Sensory evaluation; Reviews; Congenital defects; Reproduction; Language; Toxicity; Thyroid; committees; Environmental health; plains; Hormones; Toxicology; Government agencies DO - http://dx.doi.org/10.1002/bdrb.20028 ER - TY - JOUR T1 - Source identification of groundwater pollution with the aid of multivariate statistical analysis AN - 20967006; 11049283 AB - With the aid of multivariate statistical analysis, this study attempted to predict possible underlying processes, attribute their influence, and isolate the distribution of sources that might threaten groundwater quality. Tainan County, Taiwan was employed as a case study, and 34 monitoring wells were sampled for routine lab analysis. Lab data of groundwater quality including pH, EC, hardness, chloride, sulfate, ammonia, nitrate, Fe, Mn, As, Zn, TOC and TDS were subjected to factor and cluster analysis. Principal component analysis (PCA) was utilized to reflect those chemical data with the greatest correlation, whereas cluster analysis (CA) was used to evaluate the similarities of water quality in groundwater samples. By utilizing PCA, the identified four major principal components (PCs) representing 78.8% of cumulative variance were able to interpret the most information contained in the data. PC 1 reflects the dominance of salinization, which was characterized by the elevated concentrations of EC, hardness, chloride and sulfate in groundwater. PC 2 with the positive loadings of TOC and pH but negative loading of nitrate is thought to be representative of organic pollution within the aquifer. PC 3 is regarded as mineralization factor on the basis of the loadings of manganese and zinc. PC 4 shows a strong monotonic relationship with ammonia concentration in the groundwater revealing the linkage with agricultural activity. CA results illustrated that coastal area was partially salinized as a result of seawater intrusion and part of salinization zone was also subjected to the impact of mineral dissolution. JF - Water Science & Technology: Water Supply AU - Wu, T N AU - Huang, Y C AU - Lee, M S AU - Kao, C M AD - *Department of Environmental Engineering, Kun Shan University, 949 Da Wan Road, Yung-Kang City, Tainan Hsien 710, Chinese Taiwan, (E-mail: wutn[at]mail.ksut.edu.tw)**Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, 1 Hsueh Fu Road, Nei-Pu Hsiang, Pingtung Hsien 912, Chinese Taiwan***Environmental Protection Bureau of Tainan County, 78, sec 2 Chang Jung Road, Hsing-Ying City, Tainan Hsien 730, Chinese Taiwan****Institute of Environmental Engineering, National Sun Yat-sen University, 70 Lien Hi Road, Kaoshiung City 804, Chinese Taiwan Y1 - 2005 PY - 2005 DA - 2005 SP - 281 EP - 288 VL - 5 IS - 6 SN - 1606-9749, 1606-9749 KW - Aqualine Abstracts; Pollution Abstracts; Water Resources Abstracts; Environment Abstracts KW - Aquifers KW - Sulfates KW - water quality KW - dominance KW - Seawater KW - Organic Loading KW - Chlorides KW - Groundwater Pollution KW - Mineralization KW - Water supplies KW - Total organic carbon KW - Zinc KW - Statistical Analysis KW - Manganese KW - pH KW - groundwater recharge KW - Nitrates KW - principal components analysis KW - Ammonia KW - Pollution Load KW - Hydrogen Ion Concentration KW - Salinization KW - case studies KW - ISEW, Taiwan KW - Groundwater KW - salinization KW - P 2000:FRESHWATER POLLUTION KW - SW 3020:Sources and fate of pollution KW - ENA 12:Oceans & Estuaries KW - AQ 00003:Monitoring and Analysis of Water and Wastes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20967006?accountid=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=Water+Science+%26+Technology%3A+Water+Supply&rft.atitle=Source+identification+of+groundwater+pollution+with+the+aid+of+multivariate+statistical+analysis&rft.au=Wu%2C+T+N%3BHuang%2C+Y+C%3BLee%2C+M+S%3BKao%2C+C+M&rft.aulast=Wu&rft.aufirst=T&rft.date=2005-01-01&rft.volume=5&rft.issue=6&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Water+Science+%26+Technology%3A+Water+Supply&rft.issn=16069749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-10-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Sulfates; Aquifers; water quality; dominance; groundwater recharge; Nitrates; principal components analysis; Seawater; Ammonia; Chlorides; Mineralization; Water supplies; case studies; Total organic carbon; Zinc; Groundwater; Manganese; salinization; pH; Organic Loading; Statistical Analysis; Hydrogen Ion Concentration; Pollution Load; Salinization; Groundwater Pollution; ISEW, Taiwan ER - TY - JOUR T1 - Favorable scaffolds: proteins with different sequence, structure and function may associate in similar ways AN - 20863883; 6186637 AB - Proteins with similar structures may have different functions. Here, using a non-redundant two-chain protein-protein interface dataset containing 103 clusters, we show that this paradigm extends to interfaces. Whereas usually similar interfaces are obtained from globally similar chains, this is not always the case. Remarkably, in some interface clusters, although the interfaces are similar, the overall structures and functions of the chains are different. Hence, our work suggests that different folds may combinatorially assemble to yield similar local interface motifs. The preference of different folds to associate in similar ways illustrates that the paradigm is universal, whether for single chains in folding or for protein-protein association in binding. We analyze and compare the two types of clusters. Type I, with similar interfaces, similar global structures and similar functions, is better packed, less planar, has larger total and non-polar buried surface areas, better complementarity and more backbone-backbone hydrogen bonds than Type II (similar interfaces, different global structures and different functions). The dataset clusters may provide rich data for protein-protein recognition, cellular networks and drug design. In particular, they should be useful in addressing the difficult question of what the favorable ways for proteins to interact are. JF - Protein Engineering Design and Selection AU - Keskin, Ozlem AU - Nussinov, Ruth AD - Koc University, Center of Computational Biology and Bioinformatics, and College of Engineering, Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey, Basic Research Program, SAIC-Frederick, Inc., Laboratory of Experimental and Computational Biology, NCI-Frederick, Frederick, MD Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 11 EP - 24 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 18 IS - 1 SN - 1741-0126, 1741-0126 KW - Biotechnology and Bioengineering Abstracts KW - Data processing KW - Hydrogen bonding KW - Structure-function relationships KW - Surface area KW - Drug development KW - Complementarity KW - scaffolds KW - W 30925:Genetic Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20863883?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Design+and+Selection&rft.atitle=Favorable+scaffolds%3A+proteins+with+different+sequence%2C+structure+and+function+may+associate+in+similar+ways&rft.au=Keskin%2C+Ozlem%3BNussinov%2C+Ruth&rft.aulast=Keskin&rft.aufirst=Ozlem&rft.date=2005-01-01&rft.volume=18&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Protein+Engineering+Design+and+Selection&rft.issn=17410126&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-09-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Drug development; scaffolds; Data processing; Structure-function relationships; Complementarity; Surface area; Hydrogen bonding ER - TY - JOUR T1 - Inhibition of prolidase activity by nickel causes decreased growth of proline auxotrophic CHO cells AN - 20847563; 6182448 AB - Occupational exposure to nickel has been epidemiologically linked to increased cancer risk in the respiratory tract. Nickel-induced cell transformation is associated with both genotoxic and epigenetic mechanisms that are poorly understood. Prolidase [E.C.3.4.13.9] is a cytosolic Mn(II)-activated metalloproteinase that specifically hydrolyzes imidodipeptides with C-terminal proline or hydroxyproline and plays an important role in the recycling of proline for protein synthesis and cell growth. Prolidase also provides free proline as substrate for proline oxidase, whose gene is activated by p53 during apoptosis. The inhibition of prolidase activity by nickel has not yet been studied. We first showed that Ni(II) chloride specifically inhibited prolidase activity in CHO-K1 cells in situ. This interpretation was possible because CHO- K1 cells are proline auxotrophs requiring added free proline or proline released from added Gly-Pro by prolidase. In a dose-dependent fashion, Ni(II) inhibited growth on Gly-Pro but did not inhibit growth on proline, thereby showing inhibition of prolidase in situ in the absence of nonspecific toxicity. Studies using cell-free extracts showed that Ni(II) inhibited prolidase activity when present during prolidase activation with Mn(II) or during incubation with Gly- Pro. In kinetic studies, we found that Ni(II) inhibition of prolidase varied with respect to Mn(II) concentration. Analysis of these data suggested that increasing concentrations of Mn(II) stabilized the enzyme protein against Ni(II) inhibition. Because prolidase is an important enzyme in collagen metabolism, inhibition of the enzyme activity by nickel could alter the metabolism of collagen and other matrix proteins, and thereby alter cell-matrix and cell-cell interactions involved in gene expression, genomic stability, cellular differentiation, and cell proliferation. Published 2005 Wiley-Liss, Inc. JF - Journal of Cellular Biochemistry AU - Miltyk, Wojciech AU - Surazynski, Arkadiusz AU - Kasprzak, Kazimierz S AU - Fivash, Matthew J AU - Buzard, Gregory S AU - Phang, James M AD - Metabolism and Cancer Susceptibility Section, National Cancer Institute at Frederick, Frederick, Maryland 21702, phang@mail.ncifcrf.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 1210 EP - 1217 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 94 IS - 6 SN - 0730-2312, 0730-2312 KW - Health & Safety Science Abstracts KW - prolidase KW - nickel KW - CHO cells KW - proline KW - Nickel KW - Genotoxicity KW - Chlorides KW - Enzymes KW - enzymatic activity KW - Toxicity KW - Recycling KW - Cancer KW - Waste management KW - protein synthesis KW - Growth KW - Kinetics KW - Proteins KW - Occupational exposure KW - Metabolism KW - Respiratory tract KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20847563?accountid=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=Journal+of+Cellular+Biochemistry&rft.atitle=Inhibition+of+prolidase+activity+by+nickel+causes+decreased+growth+of+proline+auxotrophic+CHO+cells&rft.au=Miltyk%2C+Wojciech%3BSurazynski%2C+Arkadiusz%3BKasprzak%2C+Kazimierz+S%3BFivash%2C+Matthew+J%3BBuzard%2C+Gregory+S%3BPhang%2C+James+M&rft.aulast=Miltyk&rft.aufirst=Wojciech&rft.date=2005-01-01&rft.volume=94&rft.issue=6&rft.spage=1210&rft.isbn=&rft.btitle=&rft.title=Journal+of+Cellular+Biochemistry&rft.issn=07302312&rft_id=info:doi/10.1002%2Fjcb.20384 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-10-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Genotoxicity; Nickel; Chlorides; enzymatic activity; Enzymes; Toxicity; Recycling; Cancer; Waste management; protein synthesis; Growth; Kinetics; Proteins; Metabolism; Occupational exposure; Respiratory tract DO - http://dx.doi.org/10.1002/jcb.20384 ER - TY - JOUR T1 - Gene expression profiling in the mammary gland of rats treated with 7,12- dimethylbenz[a]anthracene AN - 20730106; 6723574 AB - Identification of molecular markers of early-stage breast cancer development is important for the diagnosis and prevention of the disease. In the present study, we used microarray analysis to examine the differential expression of genes in the rat mammary gland soon after treatment with a known chemical carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), and prior to tumor development. Six weeks after DMBA, differential expression of multiple genes involved in cell growth, differentiation and microtubule dynamics were observed. Gene expression changes were further validated by a combination of techniques, including real-time PCR, RT-PCR, Western blotting and immunohistochemistry. An inhibition of differentiation in this early stage was suggested by the lower expression of [beta]-casein and transferrin and higher expression of hsp27 in glands from DMBA-treated rats. Possible cell cycle deregulation was indicated by an increased expression of cyclin D1 and hsp86, a heat shock protein associated with cyclin D1. Prior to tumor development, DMBA increased cellular proliferation as detected by Ki-67 and stathmin immunostaining in histologically normal mammary gland. Genes regulating microtubule function, including stathmin, Ran, [alpha]-tubulin and hsp27, were all overexpressed in the mammary gland of DMBA-treated rats, raising the possibility that disruption of microtubule dynamics and abnormal mitosis may be critical events preceding breast cancer development. Several of the altered proteins, including hsp27, hsp86 and stathmin, may ultimately serve as markers of early breast cancer development. Published 2005 Wiley-Liss, Inc. JF - International Journal of Cancer AU - Papaconstantinou, Andriana D AU - Shanmugam, Ilanchezhian AU - Shan, Liang AU - Schroeder, Insa S AU - Qiu, Cunping AU - Yu, Minshu AU - Snyderwine, Elizabeth G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, elizabeth_snyderwine@nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 17 EP - 24 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 118 IS - 1 SN - 0020-7136, 0020-7136 KW - 7,12- dimethylbenz[a]anthracene KW - Genetics Abstracts; Toxicology Abstracts KW - 7,12-dimethylbenz[a]anthracene (DMBA) KW - rat mammary gland KW - microarray analysis KW - microtubule KW - heat shock protein KW - Western blotting KW - Heat shock proteins KW - Microtubules KW - Mammary gland KW - Cell cycle KW - stathmin KW - Carcinogens KW - Tumors KW - Gene expression KW - Differentiation KW - Transferrin KW - 9,10-Dimethyl-1,2-benzanthracene KW - Hsp27 protein KW - Mitosis KW - Polymerase chain reaction KW - Breast cancer KW - Immunohistochemistry KW - cyclin D1 KW - X 24190:Polycyclic hydrocarbons KW - G 07730:Development & Cell Cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20730106?accountid=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+Cancer&rft.atitle=Gene+expression+profiling+in+the+mammary+gland+of+rats+treated+with+7%2C12-+dimethylbenz%5Ba%5Danthracene&rft.au=Papaconstantinou%2C+Andriana+D%3BShanmugam%2C+Ilanchezhian%3BShan%2C+Liang%3BSchroeder%2C+Insa+S%3BQiu%2C+Cunping%3BYu%2C+Minshu%3BSnyderwine%2C+Elizabeth+G&rft.aulast=Papaconstantinou&rft.aufirst=Andriana&rft.date=2005-01-01&rft.volume=118&rft.issue=1&rft.spage=17&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.21247 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-07-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Western blotting; Microtubules; Heat shock proteins; Mammary gland; Cell cycle; stathmin; Tumors; Carcinogens; Gene expression; Differentiation; Transferrin; Mitosis; Hsp27 protein; 9,10-Dimethyl-1,2-benzanthracene; Breast cancer; Polymerase chain reaction; Immunohistochemistry; cyclin D1 DO - http://dx.doi.org/10.1002/ijc.21247 ER - TY - JOUR T1 - Is it time to change the standard of care from CT to MRI for defining the apex of the prostate to accomplish potency-sparing radiotherapy? AN - 20532628; 8067110 AB - Abstract not available. JF - International Journal of Radiation Oncology, Biology, & Physics AU - Roach III, Mack AD - Department of Radiation Oncology, University of California San Francisco, UCSF/Mt. Zion NCI-Designated Comprehensive Cancer, San Francisco, CA, roach@radonc17.ucsf.edu Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 1 EP - 2 PB - Elsevier Science, Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 61 IS - 1 SN - 0360-3016, 0360-3016 KW - Biotechnology and Bioengineering Abstracts KW - Magnetic resonance imaging KW - Radiotherapy KW - Prostate KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20532628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.atitle=Is+it+time+to+change+the+standard+of+care+from+CT+to+MRI+for+defining+the+apex+of+the+prostate+to+accomplish+potency-sparing+radiotherapy%3F&rft.au=Roach+III%2C+Mack&rft.aulast=Roach+III&rft.aufirst=Mack&rft.date=2005-01-01&rft.volume=61&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.issn=03603016&rft_id=info:doi/10.1016%2Fj.ijrobp.2004.05.038 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-04-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Magnetic resonance imaging; Radiotherapy; Prostate DO - http://dx.doi.org/10.1016/j.ijrobp.2004.05.038 ER - TY - JOUR T1 - Fixation and cryopreservation of whole blood and isolated mononuclear cells: Influence of different procedures on lymphocyte subset analysis by flow cytometry AN - 20523025; 7760290 AB - Background Immunophenotyping of whole blood (WB) and isolated peripheral blood mononuclear cells (PBMCs) is a common tool used to evaluate immune system changes in clinical studies. The development of methods that would allow preservation of samples for flow cytometric analysis is important for the extension of this technology to field testing in settings where the equipment might be not readily accessible. Methods Three-color flow cytometric analysis was used to determine percentages of T cells and their subsets (CD3+, CD4+, CD8+), B cells (CD19+), and natural killer cells (CD16+/56+) in WB and PBMCs using variations of a standard stain/fix WB staining procedure (Optilyse) that included staining following fixation and freezing of fixed samples before or after staining. Results Comparable lymphocyte subset percentages in WB or PBMCs were observed regardless of Optliyse method used (all Ps 0.8). However, differences in fluorescence intensity for several markers were observed across procedures. Compared with the standard stain/fix procedures, fix/stain decreased the mean fluorescence intensities for CD4, CD8, CD19 and CD16/56 in WB and PBMCs (P 0.03 for these markers P = 0.105 for CD8 in PBMCs). Further decreases in mean fluorescence intensity were seen with the fix/stain/freeze procedure. The stain/fix/freeze yielded intensities largely comparable to those seen with standard stain/fix procedure (P 0.13), suggesting that, when the markers of interest are known at the time of field collection, implementation of this procedure might be desirable. Fix/freeze/stain resulted in diminution of intensity in general, but they tended to be more modest than those seen for fix/stain/freeze and therefore might be applicable to field studies in instances when the specific markers of interest cannot be defined upfront. Conclusions Freezing of fixed WB and PBMCs before or after cell surface staining is a reliable method for preserving specimens in field sites for later determination of lymphocyte subset percentages, which are commonly assessed in immunodeficient and cancer patients. JF - Cytometry Part B AU - Pinto, Ligia A AU - Trivett, Matthew T AU - Wallace, Dora AU - Higgins, Jeanette AU - Baseler, Michael AU - Terabe, Masaki AU - Belyakov, Igor M AU - Berzofsky, Jay A AU - Hildesheim, Allan AD - NCI-Frederick/SAIC-Frederick, Frederick, Maryland, lpinto@ncifcrf.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 47 EP - 55 PB - John Wiley & Sons, Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 63B IS - 1 SN - 1552-4949, 1552-4949 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts KW - Cell surface KW - CD16 antigen KW - Immune system KW - Immunodeficiency KW - Stains KW - Flow cytometry KW - Peripheral blood mononuclear cells KW - CD4 antigen KW - Lymphocytes T KW - CD19 antigen KW - Leukocytes (mononuclear) KW - Fluorescence KW - Lymphocytes B KW - Natural killer cells KW - Freezing KW - CD8 antigen KW - Cryopreservation KW - CD3 antigen KW - F 06965:Immune Cells KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20523025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytometry+Part+B&rft.atitle=Fixation+and+cryopreservation+of+whole+blood+and+isolated+mononuclear+cells%3A+Influence+of+different+procedures+on+lymphocyte+subset+analysis+by+flow+cytometry&rft.au=Pinto%2C+Ligia+A%3BTrivett%2C+Matthew+T%3BWallace%2C+Dora%3BHiggins%2C+Jeanette%3BBaseler%2C+Michael%3BTerabe%2C+Masaki%3BBelyakov%2C+Igor+M%3BBerzofsky%2C+Jay+A%3BHildesheim%2C+Allan&rft.aulast=Pinto&rft.aufirst=Ligia&rft.date=2005-01-01&rft.volume=63B&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Cytometry+Part+B&rft.issn=15524949&rft_id=info:doi/10.1002%2Fcyto.b.20038 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Stains; Flow cytometry; Fluorescence; CD8 antigen; CD4 antigen; Freezing; Cryopreservation; Leukocytes (mononuclear); Lymphocytes T; Natural killer cells; CD19 antigen; CD3 antigen; CD16 antigen; Lymphocytes B; Immunodeficiency; Peripheral blood mononuclear cells; Immune system; Cell surface DO - http://dx.doi.org/10.1002/cyto.b.20038 ER - TY - JOUR T1 - Detection of low level genomic alterations by comparative genomic hybridization based on cDNA micro-arrays AN - 20492429; 7873071 AB - Motivation: The accumulation of genomic alterations is an important process in tumor formation and progression. Comparative genomic hybridization performed on cDNA arrays (cDNA aCGH) is a common method to investigate the genomic alterations on a genome-wide scale. However, when detecting low-level DNA copy number changes this technology requires the use of noise reduction strategies due to a low signal to noise ratio. Results: Currently a running average smoothing filter is the most frequently used noise reduction strategy. We analyzed this strategy theoretically and experimentally and found that it is not sensitive to very low level genomic alterations. The presence of systematic errors in the data is one of the main reasons for this failure. We developed a novel algorithm which efficiently reduces systematic noise and allows for the detection of low-level genomic alterations. The algorithm is based on comparison of the biological relevant data to data from so-called self-self hybridizations, additional experiments which contain no biological information but contain systematic errors. We find that with our algorithm the effective resolution for plus or minus 1 DNA copy number changes is about 2 Mb. For copy number changes larger than three the effective resolution is on the level of single genes. JF - Bioinformatics AU - Bilke, Sven AU - Chen, Qing-Rong AU - Whiteford, Craig C AU - Khan, Javed Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 1138 PB - Oxford University Press, Oxford Journals, Great Clarendon Street VL - 21 IS - 7 SN - 1367-4803, 1367-4803 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Filters KW - Data processing KW - Algorithms KW - DNA KW - genomics KW - Bioinformatics KW - Tumors KW - DNA microarrays KW - copy number KW - Information systems KW - G 07880:Human Genetics KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20492429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Detection+of+low+level+genomic+alterations+by+comparative+genomic+hybridization+based+on+cDNA+micro-arrays&rft.au=Bilke%2C+Sven%3BChen%2C+Qing-Rong%3BWhiteford%2C+Craig+C%3BKhan%2C+Javed&rft.aulast=Bilke&rft.aufirst=Sven&rft.date=2005-01-01&rft.volume=21&rft.issue=7&rft.spage=1138&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-01-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Filters; Data processing; DNA; Algorithms; Tumors; Bioinformatics; genomics; DNA microarrays; Information systems; copy number ER - TY - JOUR T1 - Quality assessment of microarrays: Visualization of spatial artifacts and quantitation of regional biases AN - 20349089; 9022899 AB - Background Quality-control is an important issue in the analysis of gene expression microarrays. One type of problem is regional bias, in which one region of a chip shows artifactually high or low intensities (or ratios in a two-channel array) relative to the majority of the chip. Current practice in quality assessment for microarrays does not address regional biases. Results We present methods implemented in R for visualizing regional biases and other spatial artifacts on spotted microarrays and Affymetrix chips. We also propose a statistical index to quantify regional bias and investigate its typical distribution on spotted and Affymetrix arrays. We demonstrate that notable regional biases occur on both Affymetrix and spotted arrays and that they can make a significant difference in the case of spotted microarray results. Although strong biases are also seen at the level of individual probes on Affymetrix chips, the gene expression measures are less affected, especially when the RMA method is used to summarize intensities for the probe sets. A web application program for visualization and quantitation of regional bias is provided at . Conclusion Researchers should visualize and measure the regional biases and should estimate their impact on gene expression measurements obtained. Here, we (i) introduce pictorial visualizations of the spatial biases; (ii) present for Affymetrix chips a useful resolution of the biases into two components, one related to background, the other to intensity scale factor; (iii) introduce a single parameter to reflect the global bias present across an array. We also examine the pattern distribution of such biases and conclude that algorithms based on smoothing are unlikely to compensate adequately for them. JF - BMC Bioinformatics AU - Reimers, Mark AU - Weinstein, John N AD - Genomics & Bioinformatics Group, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda Maryland, 20892 USA, reimersm@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 166 PB - BioMed Central Ltd., Middlesex House VL - 6 KW - Biotechnology and Bioengineering Abstracts KW - Gene expression KW - Statistics KW - Quality control KW - Probes KW - Algorithms KW - Bioinformatics KW - DNA microarrays KW - Quantitation KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20349089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Bioinformatics&rft.atitle=Quality+assessment+of+microarrays%3A+Visualization+of+spatial+artifacts+and+quantitation+of+regional+biases&rft.au=Reimers%2C+Mark%3BWeinstein%2C+John+N&rft.aulast=Reimers&rft.aufirst=Mark&rft.date=2005-01-01&rft.volume=6&rft.issue=&rft.spage=166&rft.isbn=&rft.btitle=&rft.title=BMC+Bioinformatics&rft.issn=1471-2105&rft_id=info:doi/10.1186%2F1471-2105-6-166 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-03-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Gene expression; Statistics; Quality control; Algorithms; Probes; Bioinformatics; Quantitation; DNA microarrays DO - http://dx.doi.org/10.1186/1471-2105-6-166 ER - TY - JOUR T1 - Flow cytometric immunophenotypic profiles of mature gamma delta T-cell malignancies involving peripheral blood and bone marrow AN - 20336373; 6433150 AB - In this study we compared clinical findings with flow cytometric immunophenotypic results in a series of patients with aggressive and indolent gamma delta T-cell malignancies with peripheral blood and/or bone marrow involvement. Gamma delta T-cell malignancies were detected based on flow cytometric demonstration of an abnormal T-cell population staining positive with T-cell receptor gamma delta and confirmed by morphologic and clinical reviews. Clinical data were obtained through chart review and discussion with the patients' physicians. Blood or bone marrow involvement was present in all patients. Hepatosplenic and cutaneous gamma delta T-cell lymphomas had an aggressive clinical course, whereas the gamma delta T-cell large granular lymphocyte (LGL) leukemias had an indolent course. Expressions of CD5, CD8, CD16, and CD57 differed in gamma delta T-cell LGL leukemia compared with hepatosplenic and cutaneous gamma delta T-cell lymphomas. Gamma delta T-cell malignancies have a poor prognosis with the exception of gamma delta T-cell LGL leukemia (indolent process). Because CD57 expression is specific for gamma delta T-cell LGL leukemias, expression of this antigen may be associated with a more indolent clinical course. Because cutaneous gamma delta T-cell lymphoma can present with peripheral blood involvement, flow cytometric evaluation of peripheral blood is important in staging these patients. JF - Cytometry Part B AU - Ahmad, Ejaz AU - Kingma, Douglas W AU - Jaffe, Elaine S AU - Schrager, Jeffrey A AU - Janik, John AU - Wilson, Wyndham AU - Stetler-Stevenson, Maryalice AD - Department of Pathology, Good Samaritan Hospital, Dayton, Ohio, stetler@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 6 EP - 12 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 67B IS - 1 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts KW - gamma delta T cell KW - lymphoma KW - large granular lymphocyte leukemia KW - flow cytometry KW - CD16 antigen KW - double prime T-cell receptor KW - Bone marrow KW - Prognosis KW - Peripheral blood KW - CD8 antigen KW - Lymphocytes KW - Cytometry KW - Flow cytometry KW - Leukemia KW - Malignancy KW - CD57 antigen KW - Reviews KW - double prime T-cell lymphoma KW - CD5 antigen KW - Lymphocytes T KW - W 30920:Tissue Engineering KW - F 06314:Clinical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20336373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytometry+Part+B&rft.atitle=Flow+cytometric+immunophenotypic+profiles+of+mature+gamma+delta+T-cell+malignancies+involving+peripheral+blood+and+bone+marrow&rft.au=Ahmad%2C+Ejaz%3BKingma%2C+Douglas+W%3BJaffe%2C+Elaine+S%3BSchrager%2C+Jeffrey+A%3BJanik%2C+John%3BWilson%2C+Wyndham%3BStetler-Stevenson%2C+Maryalice&rft.aulast=Ahmad&rft.aufirst=Ejaz&rft.date=2005-01-01&rft.volume=67B&rft.issue=1&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=Cytometry+Part+B&rft.issn=&rft_id=info:doi/10.1002%2Fcyto.b.20063 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - CD16 antigen; double prime T-cell receptor; Prognosis; Bone marrow; Peripheral blood; Lymphocytes; CD8 antigen; Cytometry; Flow cytometry; Leukemia; Malignancy; CD57 antigen; double prime T-cell lymphoma; Reviews; CD5 antigen; Lymphocytes T DO - http://dx.doi.org/10.1002/cyto.b.20063 ER - TY - JOUR T1 - Pharmacologic profiling of transcriptional targets deciphers promoter logic AN - 20247737; 6737246 AB - The blueprint for cellular diversity and response to environmental change is encoded in the cis-acting regulatory sequences of most genes. Deciphering this'cis-regulatory code' requires multivariate data sets that examine how these regions coordinate transcription in response to diverse environmental stimuli and therapeutic treatments. We describe a transcriptional approach that profiles the activation of multiple transcriptional targets against combinatorial arrays of therapeutic and signal transducing agents. Application of this approach demonstrates how cis-element composition and promoter context combine to influence transcription downstream of mitogen-induced signaling networks. Computational dissection of these transcriptional profiles in activated T cells uncovers a novel regulatory synergy between IGF-1 and CD28 costimulation that modulates NF- Kappa B and AP1 pathways through signaling cascades sensitive to cyclosporin A and wortmannin. This approach provides a broader view of the hierarchical signal integration governing gene expression and will facilitate a practical design of combinatorial therapeutic strategies for exploiting critical control points in transcriptional regulation. JF - Pharmacogenomics Journal AU - Freebern, W J AU - Haggerty, C M AU - Montano, I AU - McNutt, M C AU - Collins, I AU - Graham, A AU - Chandramouli, GVR AU - Stewart, D H AU - Biebuyck, HA AU - Taub, D D AU - Gardner, K AD - Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, The Advanced Technology Center, Room 133, 8717 Grovemont Circle, Bethesda, MD 20892-4605, USA, gardnerk@nnail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 305 EP - 323 VL - 5 IS - 5 SN - 1470-269X, 1470-269X KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Insulin-like growth factor I KW - Data processing KW - Regulatory sequences KW - Activator protein 1 KW - Computer applications KW - NF- Kappa B protein KW - Transcription factors KW - Lymphocytes T KW - Cyclosporin A KW - Transcription activation KW - Signal transduction KW - Wortmannin KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20247737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenomics+Journal&rft.atitle=Pharmacologic+profiling+of+transcriptional+targets+deciphers+promoter+logic&rft.au=Freebern%2C+W+J%3BHaggerty%2C+C+M%3BMontano%2C+I%3BMcNutt%2C+M+C%3BCollins%2C+I%3BGraham%2C+A%3BChandramouli%2C+GVR%3BStewart%2C+D+H%3BBiebuyck%2C+HA%3BTaub%2C+D+D%3BGardner%2C+K&rft.aulast=Freebern&rft.aufirst=W&rft.date=2005-01-01&rft.volume=5&rft.issue=5&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=Pharmacogenomics+Journal&rft.issn=1470269X&rft_id=info:doi/10.1038%2Fsj.tpj.6500325 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Insulin-like growth factor I; Data processing; Regulatory sequences; Transcription factors; Activator protein 1; Lymphocytes T; Cyclosporin A; Computer applications; Transcription activation; Wortmannin; NF- Kappa B protein; Signal transduction DO - http://dx.doi.org/10.1038/sj.tpj.6500325 ER - TY - JOUR T1 - Nano-sized MRI contrast agents with dendrimer cores AN - 20219678; 7199784 AB - Gadolinium-based MRI contrast agents (CAs) can be effective at a 100-fold lower concentration of Gadolinium ions in comparison to the concentration of Iodine atoms required for CT imaging. Therefore, a number of dendrimer based macromolecular MRI CAs of various sizes and properties prepared employing relatively simple chemistry are readily available that can provide sufficient contrast enhancement for various applications. Molecules up to 20 nm in diameter behave differently in the body depending on their size. Even if these molecules possess similar chemical properties, small changes in size can greatly impact their pharmacokinetics. Changes in molecular size up to 15 nm in diameter altered permeability across the vascular wall, excretion route, and recognition by the reticuloendothelial system. Smaller sized polyamidoamine (PAMAM) dendrimer-based contrast agents, i.e., less than 3 nm in diameter, easily "leak" across the vascular wall resulting in rapid perfusion throughout the body. Contrast agents 3-6 nm in diameter were quickly excreted through the kidney indicating these agents to be potentially suitable as functional renal contrast agents. Contrast agents 7-12 nm in diameter were retained in circulation and were better suited for use as blood pool contrast agents. Hydrophobic variants of CAs formed with polypropylenimine diaminobutane (DAB) dendrimer cores quickly accumulated in the liver and potentially have use as liver contrast agents. Larger hydrophilic agents have suitable characteristics for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents and might also be employed as either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy. JF - Advanced Drug Delivery Reviews AU - Kobayashi, Hisataka AU - Brechbiel, Martin W AD - Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 1B40, 10 Center Drive, Bethesda, MD 20892-1088, USA, Kobayash@mail.nih.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 2271 EP - 2286 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 57 IS - 1 SN - 0169-409X, 0169-409X KW - Biotechnology Research Abstracts (through 1992) KW - Drug delivery KW - Ions KW - Macromolecules KW - Perfusion KW - Monoclonal antibodies KW - polyamidoamines KW - Gadolinium KW - Magnetic resonance imaging KW - Hydrophobicity KW - Reticuloendothelial system KW - Pharmacokinetics KW - Neutrons KW - Blood KW - Avidin KW - Permeability KW - Reviews KW - Computed tomography KW - Liver KW - Kidney KW - Contrast media KW - Iodine KW - Excretion KW - Vascular system KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20219678?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advanced+Drug+Delivery+Reviews&rft.atitle=Nano-sized+MRI+contrast+agents+with+dendrimer+cores&rft.au=Kobayashi%2C+Hisataka%3BBrechbiel%2C+Martin+W&rft.aulast=Kobayashi&rft.aufirst=Hisataka&rft.date=2005-01-01&rft.volume=57&rft.issue=1&rft.spage=2271&rft.isbn=&rft.btitle=&rft.title=Advanced+Drug+Delivery+Reviews&rft.issn=0169409X&rft_id=info:doi/10.1016%2Fj.addr.2005.09.016 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Contrast media; Magnetic resonance imaging; Kidney; Gadolinium; Liver; Vascular system; Macromolecules; Hydrophobicity; Reticuloendothelial system; Neutrons; Ions; Perfusion; Excretion; Permeability; Reviews; Avidin; Monoclonal antibodies; Iodine; Drug delivery; Pharmacokinetics; polyamidoamines; Computed tomography; Blood DO - http://dx.doi.org/10.1016/j.addr.2005.09.016 ER - TY - JOUR T1 - Effects of DNA mass on multiple displacement whole genome amplification and genotyping performance AN - 20197116; 6491127 AB - Whole genome amplification (WGA) promises to eliminate practical molecular genetic analysis limitations associated with genomic DNA (gDNA) quantity. We evaluated the performance of multiple displacement amplification (MDA) WGA using gDNA extracted from lymphoblastoid cell lines (N = 27) with a range of starting gDNA input of 1-200 ng into the WGA reaction. Yield and composition analysis of whole genome amplified DNA (wgaDNA) was performed using three DNA quantification methods (OD, PicoGreen super( registered )uand RT-PCR). Two panels of N = 15 STR (using the AmpFliSTR super( registered )uIdentifiler super( registered )upanel) and N = 49 SNP (TaqMan super( registered )u) genotyping assays were performed on each gDNA and wgaDNA sample in duplicate. gDNA and wgaDNA masses of 1, 4 and 20 ng were used in the SNP assays to evaluate the effects of DNA mass on SNP genotyping assay performance. A total of N = 6,880 STR and N = 56,448 SNP genotype attempts provided adequate power to detect differences in STR and SNP genotyping performance between gDNA and wgaDNA, and among wgaDNA produced from a range of gDNA templates inputs. The proportion of double-stranded wgaDNA and human-specific PCR amplifiable wgaDNA increased with increased gDNA input into the WGA reaction. Increased amounts of gDNA input into the WGA reaction improved wgaDNA genotyping performance. Genotype completion or genotype concordance rates of wgaDNA produced from all gDNA input levels were observed to be reduced compared to gDNA, although the reduction was not always statistically significant. Reduced wgaDNA genotyping performance was primarily due to the increased variance of allelic amplification, resulting in loss of heterozygosity or increased undetermined genotypes. MDA WGA produces wgaDNA from no template control samples; such samples exhibited substantial false-positive genotyping rates. The amount of gDNA input into the MDA WGA reaction is a critical determinant of genotyping performance of wgaDNA. At least 10 ng of lymphoblastoid gDNA input into MDA WGA is required to obtain wgaDNA TaqMan super( registered )uSNP assay genotyping performance equivalent to that of gDNA. Over 100 ng of lymphoblastoid gDNA input into MDA WGA is required to obtain optimal STR genotyping performance using the AmpFliSTR super( registered )uIdentifiler super( registered )upanel from wgaDNA equivalent to that of gDNA. JF - BMC Biotechnology AU - Bergen, Andrew W AU - Qi, Ying AU - Haque, Kashif A AU - Welch, Robert A AU - Chanock, Stephen J AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 5 IS - 1 KW - Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Biotechnology and Bioengineering Abstracts KW - Article No. 24 KW - Genomes KW - Lymphoblastoid cell lines KW - Single-nucleotide polymorphism KW - Genotyping KW - Genetic analysis KW - Statistical analysis KW - Polymerase chain reaction KW - Genotypes KW - genomics KW - Loss of heterozygosity KW - G 07730:Development & Cell Cycle KW - N 14810:Methods KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20197116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Biotechnology&rft.atitle=Effects+of+DNA+mass+on+multiple+displacement+whole+genome+amplification+and+genotyping+performance&rft.au=Bergen%2C+Andrew+W%3BQi%2C+Ying%3BHaque%2C+Kashif+A%3BWelch%2C+Robert+A%3BChanock%2C+Stephen+J&rft.aulast=Bergen&rft.aufirst=Andrew&rft.date=2005-01-01&rft.volume=5&rft.issue=1&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Biotechnology&rft.issn=1472-6750&rft_id=info:doi/10.1186%2F1472-6750-5-24 L2 - http://www.biomedcentral.com/1472-6750/5/24 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Genomes; Lymphoblastoid cell lines; Single-nucleotide polymorphism; Genotyping; Genetic analysis; Statistical analysis; Polymerase chain reaction; genomics; Genotypes; Loss of heterozygosity DO - http://dx.doi.org/10.1186/1472-6750-5-24 ER - TY - JOUR T1 - Emerging infectious diseases: A 10-year perspective from the National Institute of Allergy and Infectious Diseases AN - 20104487; 6706728 AB - Although optimists once imagined that serious infectious disease threats would by now be conquered, newly emerging (e.g., severe acute respiratory syndrome [SARS]), re-emerging (e.g., West Nile virus), and even deliberately disseminated infectious diseases (e.g., anthrax bioterrorism) continue to appear throughout the world. Over the past decade, the global effort to identify and characterize infectious agents, decipher the underlying pathways by which they cause disease, and develop preventive measures and treatments for many of the world's most dangerous pathogens has resulted in considerable progress. Intramural and extramural investigators supported by the National Institute of Allergy and Infectious Diseases (NIAID) have contributed substantially to this effort. This overview highlights selected NIAID-sponsored research advances over the past decade, with a focus on progress in combating HIV/AIDS, malaria, tuberculosis, influenza, SARS, West Nile virus, and potential bioterror agents. Many basic research discoveries have been translated into novel diagnostics, antiviral and antimicrobial compounds, and vaccines, often with extraordinary speed. JF - International Journal of Risk and Safety in Medicine AU - Fauci, A S AU - Touchette, NA AU - Folkers, G K AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Building 31, Room 7A05, Bethesda, MD 20892, USA, ntouchette@niaid.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 157 EP - 167 VL - 17 IS - 3-4 SN - 0924-6479, 0924-6479 KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Mycobacterium KW - bioterrorism KW - Severe acute respiratory syndrome KW - Malaria KW - Pathogens KW - Antimicrobial agents KW - Influenza KW - Hypersensitivity KW - Infectious diseases KW - Human immunodeficiency virus KW - Reviews KW - Anthrax KW - Tuberculosis KW - Vaccines KW - SARS coronavirus KW - West Nile virus KW - A 01340:Antibiotics & Antimicrobials KW - V 22360:AIDS and HIV KW - J 02320:Cell Biology KW - K 03420:Plant Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20104487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Risk+and+Safety+in+Medicine&rft.atitle=Emerging+infectious+diseases%3A+A+10-year+perspective+from+the+National+Institute+of+Allergy+and+Infectious+Diseases&rft.au=Fauci%2C+A+S%3BTouchette%2C+NA%3BFolkers%2C+G+K&rft.aulast=Fauci&rft.aufirst=A&rft.date=2005-01-01&rft.volume=17&rft.issue=3-4&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Risk+and+Safety+in+Medicine&rft.issn=09246479&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-07-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Acquired immune deficiency syndrome; bioterrorism; Severe acute respiratory syndrome; Malaria; Pathogens; Antimicrobial agents; Influenza; Hypersensitivity; Infectious diseases; Reviews; Anthrax; Tuberculosis; Vaccines; Mycobacterium; Human immunodeficiency virus; West Nile virus; SARS coronavirus ER - TY - JOUR T1 - Research hurdles complicating the analysis of infertility treatment and child health AN - 19935242; 6117597 AB - Research aimed at the empirical evaluation of infertility treatment including assisted reproductive technologies (ART) on child health and development is hampered by investigators' inability to methodologically separate possible treatment effects from underlying fecundity impairments. While the literature continues to identify ART as a risk factor for many child health outcomes, less attention has been paid to the methodologic rigor needed to answer this question. We identify aspects of fecundity and the nuances of medical practice that need to be considered and captured when designing epidemiologic investigations aimed at assessing ART and child health. These include: (i) the use of prospective study designs in which the unit of analysis (cycle versus individual versus couple) is defined; (ii) data collection on relevant time-varying covariates at, before and during treatment; and (iii) the use of statistical techniques appropriate for hierarchical data and correlated exposures. While none of these issues in and by itself is unique to ART research, attention to these issues has been lacking in much of the published research limiting our ability to evaluate health consequences for children. Longitudinal studies of children conceived with ART will benefit from attention to these issues and, hopefully, produce answers to lingering questions about safety. JF - Human Reproduction AU - Buck Louis, GM AU - Schisterman, E F AU - Dukic, V M AU - Schieve, LA AD - Epidemiology Branch, Division of Epidemiology, Statistics & Prevention Research, National Institute of Child Health & Human Development, The National Institutes of Health, Department of Health & Human Services, 6100 Executive Boulevard, Room 7B03, Rockville, MD Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 12 EP - 18 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 20 IS - 1 SN - 0268-1161, 0268-1161 KW - Sustainability Science Abstracts; Human Population KW - Longitudinal studies KW - Infertility KW - Data collection KW - Fecundity KW - Health KW - Research KW - Reproductive technology KW - Children KW - Attention KW - M3 1010:Issues in Sustainable Development KW - M1 125:Population Health-Environment Relations UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19935242?accountid=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=Human+Reproduction&rft.atitle=Research+hurdles+complicating+the+analysis+of+infertility+treatment+and+child+health&rft.au=Buck+Louis%2C+GM%3BSchisterman%2C+E+F%3BDukic%2C+V+M%3BSchieve%2C+LA&rft.aulast=Buck+Louis&rft.aufirst=GM&rft.date=2005-01-01&rft.volume=20&rft.issue=1&rft.spage=12&rft.isbn=&rft.btitle=&rft.title=Human+Reproduction&rft.issn=02681161&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-01-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Longitudinal studies; Infertility; Data collection; Fecundity; Health; Reproductive technology; Research; Children; Attention ER - TY - JOUR T1 - Intramucosal Bacteria in Colon Cancer and Their Elimination by Probiotic Strain Enterococcus faecium M-74 with Organic Selenium AN - 19833099; 6702312 AB - Intraepithelial bacteria were isolated by the gentamicin protection assay (GPA) from biopsy samples obtained at colonoscopy (colon cancer, n = 10 patients; colonic adenoma, n = 20; control group, n = 20; cancer patients without gastrointestinal tract GIT malignancy, n = 10). After a three-month administration of E. faecium M-74 to patients with positive GPA biopsies, 172 biopsy specimens from 60 patients were examined with the GPA. The number of biopsies with intracellular bacteria was significantly higher in adenoma and carcinoma group than in control group (26 vs. 10%; p = 0.004); in cancer patients without GIT malignancy the difference was nonsignificant. E. faecium M-74 was also administered to 5 patients with colonic adenoma; according to a control colonoscopy the number of biopsies with intracellular bacteria was significantly lower after probiotic administration (48 vs. 16%; p = 0.03). A striking prevalence of intraepithelial bacteria was also showed in patients with large bowel adenoma and carcinoma. The administration of probiotic strain M-74 can thus be considered to be an effective and promising method for elimination of pathogenic bacteria in the case of inflammatory bowel disease and colon cancer. JF - Folia Microbiologica AU - Mego, M AU - Majek, J AU - Koncekova, R AU - Ebringer, L AU - Ciernikova, S AU - Rauko, P AU - Kovac, M AU - Trupl, J AU - Slezak, P AU - Zajac, V AD - Department of Medical Oncology, National Cancer Institute, Klenova 1, 833 10 Bratislava, Slovakia, misomego@mediclub.sk Y1 - 2005 PY - 2005 DA - 2005 SP - 443 EP - 447 VL - 50 IS - 5 SN - 0015-5632, 0015-5632 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - probiotics KW - Biopsy KW - Colon cancer KW - Enterococcus faecium KW - Carcinoma KW - Gentamicin KW - Selenium KW - Malignancy KW - Digestive tract KW - Inflammatory bowel diseases KW - Intestine KW - Gastrointestinal tract KW - Adenoma KW - J 02841:Microflora KW - A 01330:Food Microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19833099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Folia+Microbiologica&rft.atitle=Intramucosal+Bacteria+in+Colon+Cancer+and+Their+Elimination+by+Probiotic+Strain+Enterococcus+faecium+M-74+with+Organic+Selenium&rft.au=Mego%2C+M%3BMajek%2C+J%3BKoncekova%2C+R%3BEbringer%2C+L%3BCiernikova%2C+S%3BRauko%2C+P%3BKovac%2C+M%3BTrupl%2C+J%3BSlezak%2C+P%3BZajac%2C+V&rft.aulast=Mego&rft.aufirst=M&rft.date=2005-01-01&rft.volume=50&rft.issue=5&rft.spage=443&rft.isbn=&rft.btitle=&rft.title=Folia+Microbiologica&rft.issn=00155632&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Gentamicin; Selenium; Malignancy; Digestive tract; Inflammatory bowel diseases; Intestine; probiotics; Biopsy; Gastrointestinal tract; Colon cancer; Adenoma; Carcinoma; Enterococcus faecium ER - TY - JOUR T1 - Long dynamics simulations of proteins using atomistic force fields and a continuum representation of solvent effects: Calculation of structural and dynamic properties AN - 19817780; 6383975 AB - Long dynamics simulations were carried out on the B1 immunoglobulin-binding domain of streptococcal protein G (ProtG) and bovine pancreatic trypsin inhibitor (BPTI) using atomistic descriptions of the proteins and a continuum representation of solvent effects. To mimic frictional and random collision effects, Langevin dynamics (LD) were used. The main goal of the calculations was to explore the stability of tens-of-nanosecond trajectories as generated by this molecular mechanics approximation and to analyze in detail structural and dynamical properties. Conformational fluctuations, order parameters, cross correlation matrices, residue solvent accessibilities, pKa values of titratable groups, and hydrogen-bonding (HB) patterns were calculated from all of the trajectories and compared with available experimental data. The simulations comprised over 40 ns per trajectory for ProtG and over 30 ns per trajectory for BPTI. For comparison, explicit water molecular dynamics simulations (EW/MD) of 3 ns and 4 ns, respectively, were also carried out. Two continuum simulations were performed on each protein using the CHARMM program, one with the all-atom PAR22 representation of the protein force field (here referred to as PAR22/LD simulations) and the other with the modifications introduced by the recently developed CMAP potential (CMAP/LD simulations). The explicit solvent simulations were performed with PAR22 only. Solvent effects are described by a continuum model based on screened Coulomb potentials (SCP) reported earlier, i.e. the SCP- based implicit solvent model (SCP-ISM). For ProtG, both the PAR22/LD and the CMAP/LD 40-ns trajectories were stable, yielding C sub( alpha ) root mean square deviations (RMSD) of about 1.0 and 0.8 Aa respectively along the entire simulation time, compared to 0.8 Aa for the EW/MD simulation. For BPTI, only the CMAP/LD trajectory was stable for the entire 30-ns simulation, with a C sub( alpha ) RMSD of [ap]1.4 Aa, while the PAR22/LD trajectory became unstable early in the simulation, reaching a C sub( alpha ) RMSD of about 2.7 Aa and remaining at this value until the end of the simulation; the C sub( alpha ) RMSD of the EW/MD simulation was about 1.5 Aa. The source of the instabilities of the BPTI trajectories in the PAR22/LD simulations was explored by an analysis of the backbone torsion angles. To further validate the findings from this analysis of BPTI, a 35-ns SCP-ISM simulation of Ubiquitin (Ubq) was carried out. For this protein, the CMAP/LD simulation was stable for the entire simulation time (C sub( alpha ) RMSD of [ap]1.0 Aa), while the PAR22/LD trajectory showed a trend similar to that in BPTI, reaching a C sub( alpha ) RMSD of [ap]1.5 Aa at 7 ns. All the calculated properties were found to be in agreement with the corresponding experimental values, although local deviations were also observed. HB patterns were also well reproduced by all the continuum solvent simulations with the exception of solvent-exposed side chain-side chain (sc-sc) HB in ProtG, where several of the HB interactions observed in the crystal structure and in the EW/MD simulation were lost. The overall analysis reported in this work suggests that the combination of an atomistic representation of a protein with a CMAP/CHARMM force field and a continuum representation of solvent effects such as the SCP-ISM provides a good description of structural and dynamic properties obtained from long computer simulations. Although the SCP-ISM simulations (CMAP/LD) reported here were shown to be stable and the properties well reproduced, further refinement is needed to attain a level of accuracy suitable for more challenging biological applications, particularly the study of protein- protein interactions. Proteins 2005. JF - Proteins: Structure, Function & Bioinformatics AU - Li, Xianfeng AU - Hassan, Sergio A AU - Mehler, Ernest L AD - Department of Physiology and Biophysics, Weill Medical College, Cornell University, New York, New York, mago@helix.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 464 EP - 484 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 60 IS - 3 SN - 0887-3585, 0887-3585 KW - Microbiology Abstracts B: Bacteriology KW - continuum model KW - implicit solvent model KW - screened Coulomb potentials KW - Langevin dynamics KW - molecular dynamics simulation KW - protein G KW - BPTI KW - Ubiquitin KW - Streptococcus KW - Protein kinase A KW - Mathematical models KW - Data processing KW - Trypsin KW - Pancreas KW - Solvents KW - Single-cell protein KW - Models KW - Protein structure KW - streptococcal protein G KW - Crystal structure KW - Bioinformatics KW - Protein interaction KW - J 02450:Ecology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19817780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteins%3A+Structure%2C+Function+%26+Bioinformatics&rft.atitle=Long+dynamics+simulations+of+proteins+using+atomistic+force+fields+and+a+continuum+representation+of+solvent+effects%3A+Calculation+of+structural+and+dynamic+properties&rft.au=Li%2C+Xianfeng%3BHassan%2C+Sergio+A%3BMehler%2C+Ernest+L&rft.aulast=Li&rft.aufirst=Xianfeng&rft.date=2005-01-01&rft.volume=60&rft.issue=3&rft.spage=464&rft.isbn=&rft.btitle=&rft.title=Proteins%3A+Structure%2C+Function+%26+Bioinformatics&rft.issn=08873585&rft_id=info:doi/10.1002%2Fprot.20470 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Protein kinase A; Data processing; Mathematical models; Trypsin; Pancreas; Solvents; Single-cell protein; Models; Protein structure; streptococcal protein G; Crystal structure; Bioinformatics; Protein interaction; Ubiquitin; Streptococcus DO - http://dx.doi.org/10.1002/prot.20470 ER - TY - JOUR T1 - Identifying natural substrates for chaperonins using a sequence-based approach AN - 19803591; 6172562 AB - The Escherichia coli chaperonin machinery, GroEL, assists the folding of a number of proteins. We describe a sequence-based approach to identify the natural substrate proteins (SPs) for GroEL. Our method is based on the hypothesis that natural SPs are those that contain patterns of residues similar to those found in either GroES mobile loop and/or strongly binding peptide in complex with GroEL. The method is validated by comparing the predicted results with experimentally determined natural SPs for GroEL. We have searched for such patterns in five genomes. In the E. coli genome, we identify 1422 (about one- third) sequences that are putative natural SPs. In Saccharomyces cerevisiae, 2885 (32%) of sequences can be natural substrates for Hsp60, which is the analog of GroEL. The precise number of natural SPs is shown to be a function of the number of contacts an SP makes with the apical domain (N sub(C)) and the number of binding sites (N sub(B)) in the oligomer with which it interacts. For known SPs for GroEL, we find approximately 4 < N sub(C) < 5 and 2 < N sub(B) < 4. A limited analysis of the predicted binding sequences shows that they do not adopt any preferred secondary structure. Our method also predicts the putative binding regions in the identified SPs. The results of our study show that a variety of SPs, associated with diverse functions, can interact with GroEL. JF - Protein Science AU - Stan, George AU - Brooks, Bernard R AU - Lorimer, George H AU - Thirumalai, D AD - Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, Maryland Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 193 EP - 201 PB - Cold Spring Harbor Laboratory Press, [mailto:cshpress@cshl.org], [URL:http://www.cshl.org/] VL - 14 IS - 1 SN - 0961-8368, 0961-8368 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts B: Bacteriology KW - Genomes KW - Protein structure KW - Protein folding KW - Chaperonins KW - Secondary structure KW - Escherichia coli KW - Hsp60 protein KW - Substance P KW - Saccharomyces cerevisiae KW - J 02310:Genetics & Taxonomy KW - K 03330:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19803591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+Science&rft.atitle=Identifying+natural+substrates+for+chaperonins+using+a+sequence-based+approach&rft.au=Stan%2C+George%3BBrooks%2C+Bernard+R%3BLorimer%2C+George+H%3BThirumalai%2C+D&rft.aulast=Stan&rft.aufirst=George&rft.date=2005-01-01&rft.volume=14&rft.issue=1&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=Protein+Science&rft.issn=09618368&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 - Protein structure; Genomes; Protein folding; Secondary structure; Chaperonins; Hsp60 protein; Substance P; Escherichia coli; Saccharomyces cerevisiae ER - TY - JOUR T1 - Origin-independent plasmid replication occurs in vaccinia virus cytoplasmic factories and requires all five known poxvirus replication factors AN - 19771076; 7156423 AB - Background Replication of the vaccinia virus genome occurs in cytoplasmic factory areas and is dependent on the virus-encoded DNA polymerase and at least four additional viral proteins. DNA synthesis appears to start near the ends of the genome, but specific origin sequences have not been defined. Surprisingly, transfected circular DNA lacking specific viral sequences is also replicated in poxvirus-infected cells. Origin-independent plasmid replication depends on the viral DNA polymerase, but neither the number of additional viral proteins nor the site of replication has been determined. Results Using a novel real-time polymerase chain reaction assay, we detected a >400-fold increase in newly replicated plasmid in cells infected with vaccinia virus. Studies with conditional lethal mutants of vaccinia virus indicated that each of the five proteins known to be required for viral genome replication was also required for plasmid replication. The intracellular site of replication was determined using a plasmid containing 256 repeats of the Escherichia coli lac operator and staining with an E. coli lac repressor-maltose binding fusion protein followed by an antibody to the maltose binding protein. The lac operator plasmid was localized in cytoplasmic viral factories delineated by DNA staining and binding of antibody to the viral uracil DNA glycosylase, an essential replication protein. In addition, replication of the lac operator plasmid was visualized continuously in living cells infected with a recombinant vaccinia virus that expresses the lac repressor fused to enhanced green fluorescent protein. Discrete cytoplasmic fluorescence was detected in cytoplasmic juxtanuclear sites at 6 h after infection and the area and intensity of fluorescence increased over the next several hours. Conclusion Replication of a circular plasmid lacking specific poxvirus DNA sequences mimics viral genome replication by occurring in cytoplasmic viral factories and requiring all five known viral replication proteins. Therefore, small plasmids may be used as surrogates for the large poxvirus genome to study trans-acting factors and mechanism of viral DNA replication. JF - Virology Journal AU - De Silva, Frank S AU - Moss, Bernard AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0445, USA Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 2 SN - 1743-422X, 1743-422X KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - Article No. 23 KW - Genomes KW - DNA biosynthesis KW - Circular DNA KW - Fluorescence KW - Replication KW - Nucleotide sequence KW - DNA glycosylase KW - Green fluorescent protein KW - Infection KW - Plasmids KW - Lethal mutant KW - Operators KW - Antibodies KW - Vaccinia virus KW - Lac repressor KW - Poxvirus KW - DNA-directed DNA polymerase KW - Uracil-DNA glycosidase KW - Escherichia coli KW - Polymerase chain reaction KW - Fusion protein KW - maltose-binding protein KW - J 02310:Genetics & Taxonomy KW - V 22320:Replication KW - G 07770:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19771076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology+Journal&rft.atitle=Origin-independent+plasmid+replication+occurs+in+vaccinia+virus+cytoplasmic+factories+and+requires+all+five+known+poxvirus+replication+factors&rft.au=De+Silva%2C+Frank+S%3BMoss%2C+Bernard&rft.aulast=De+Silva&rft.aufirst=Frank&rft.date=2005-01-01&rft.volume=2&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Virology+Journal&rft.issn=1743422X&rft_id=info:doi/10.1186%2F1743-422X-2-23 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Genomes; DNA biosynthesis; Circular DNA; Fluorescence; Replication; DNA glycosylase; Nucleotide sequence; Green fluorescent protein; Plasmids; Infection; Lethal mutant; Operators; Antibodies; Lac repressor; Uracil-DNA glycosidase; DNA-directed DNA polymerase; Polymerase chain reaction; Fusion protein; maltose-binding protein; Vaccinia virus; Poxvirus; Escherichia coli DO - http://dx.doi.org/10.1186/1743-422X-2-23 ER - TY - JOUR T1 - Development of antibodies to human embryonic stem cell antigens AN - 19768063; 6573725 AB - Using antibodies to specific protein antigens is the method of choice to assign and identify cell lineage through simultaneous analysis of surface molecules and intracellular markers. Embryonic stem cell research can be benefited from using antibodies specific to transcriptional factors/markers that contribute to the "stemness" phenotype or critical for cell lineage. In this report, we have developed and validated antibodies (either monoclonal or polyclonal) specific to human embryonic stem cell antigens and early differentiation transcriptional factors/markers that are critical for cell differentiation into definite lineage. These antibodies enable stem cell biologists to conveniently identify stem cell characteristics and to quantitatively assess differentiation. JF - BMC Developmental Biology AU - Cai, Jingli AU - Olson, Judith M AU - Rao, Mahendra S AU - Stanley, Marisa AU - Taylor, Eva AU - Ni, Hsiao-Tzu AD - Stem Cell Biology Unit, Laboratory of Neurosciences, National Institute on Aging, 333 Cassell Dr, Rm406A, Baltimore, MD 21224, USA Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 5 IS - 1 SN - 1471-213X, 1471-213X KW - Biotechnology and Bioengineering Abstracts KW - Article No. 26 KW - Cell lineage KW - Differentiation KW - Antibodies KW - Stem cells KW - Embryo cells KW - Monoclonal antibodies KW - Transcription factors KW - Transcription KW - W 30940:Products UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19768063?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Developmental+Biology&rft.atitle=Development+of+antibodies+to+human+embryonic+stem+cell+antigens&rft.au=Cai%2C+Jingli%3BOlson%2C+Judith+M%3BRao%2C+Mahendra+S%3BStanley%2C+Marisa%3BTaylor%2C+Eva%3BNi%2C+Hsiao-Tzu&rft.aulast=Cai&rft.aufirst=Jingli&rft.date=2005-01-01&rft.volume=5&rft.issue=1&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Developmental+Biology&rft.issn=1471213X&rft_id=info:doi/10.1186%2F1471-213X-5-26 L2 - http://www.biomedcentral.com/1471-213X/5/26 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Cell lineage; Differentiation; Stem cells; Antibodies; Embryo cells; Monoclonal antibodies; Transcription factors; Transcription DO - http://dx.doi.org/10.1186/1471-213X-5-26 ER - TY - JOUR T1 - Medical Nanotechnology: Shortening Clinical Trials and Regulatory Pathways? AN - 19695109; 7478911 AB - Nanotechnology, the science of creating structures, devices, and systems with a length scale of approximately 1-100 nanometers, is poised to have a revolutionary effect on biomedical research and clinical science. By operating at the same scale as most biomacromolecules, nanoscale devices can afford a detailed view of the molecules and events that drive cellular systems and that lie at the heart of disease, and thus, nanotechnology can impact the drug discovery, development, and clinical testing of novel pharmaceuticals. Already, nanoscale drug delivery vehicles are in clinical use, but those successes represent just one way in which nanotechnology will prove useful. One promising nanoscale technology under development may provide real-time, in vivo measurements of apoptosis, and thus may afford an early signal of therapeutic efficacy, both in human clinical trials and in preclinical screening. Microfluidic systems, built of nanoscale components, can enable a host of rapid, massively parallel, high-throughput screening systems, while nanoscale sensors in a wide variety of formats are ready to provide multiplexed biochemical and genetic measurements in living systems. These advances could be utilized to shave time and expense from multiple stages of the drug discovery and development effort. JF - BioDrugs AU - Ferrari, Mauro AU - Downing, Gregory AD - 1 National Cancer Institute, Bethesda, Maryland, USA Y1 - 2005 PY - 2005 DA - 2005 SP - 203 EP - 210 PB - Adis International Ltd., 41 Centorian Drive Private Bay 65901, Mairangi Bay Auckland 10 New Zealand, [mailto:sportsmed@adis.co.nz], [URL:http://www.adis.com] VL - 19 IS - 4 SN - 1173-8804, 1173-8804 KW - Biotechnology and Bioengineering Abstracts KW - Nanoparticles KW - Research and development KW - Drug discovery KW - Drug delivery KW - Microfluidics KW - Apoptosis KW - Pharmaceuticals KW - high-throughput screening KW - Clinical trials KW - nanotechnology KW - Heart diseases KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19695109?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioDrugs&rft.atitle=Medical+Nanotechnology%3A+Shortening+Clinical+Trials+and+Regulatory+Pathways%3F&rft.au=Ferrari%2C+Mauro%3BDowning%2C+Gregory&rft.aulast=Ferrari&rft.aufirst=Mauro&rft.date=2005-01-01&rft.volume=19&rft.issue=4&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=BioDrugs&rft.issn=11738804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Drug delivery; Drug discovery; Microfluidics; Apoptosis; Pharmaceuticals; high-throughput screening; Clinical trials; Heart diseases; nanotechnology ER - TY - JOUR T1 - Nomenclature-Based Data Retrieval without Prior Annotation: Facilitating Biomedical Data Integration with Fast Doublet Matching AN - 19552158; 8720431 AB - Assigning nomenclature codes to biomedical data is an arduous, expensive and error-prone task. Data records are coded to to provide a common representation of contained concepts, allowing facile retrieval of records via a standard terminology. In the medical field, cancer registrars, nurses, pathologists, and private clinicians all understand the importance of annotating medical records with vocabularies that codify the names of diseases, procedures, billing categories, etc. Molecular biologists need codified medical records so that they can discover or validate relationships between experimental data and clinical data.This paper introduces a new approach to retrieving data records without prior coding. The approach achieves the same result as a search over pre-coded records. It retrieves all records that contain any terms that are synonymous with a user's query-term. A recently described fast algorithm (the doublet method) permits quick iterative searches over every synonym for any term from any nomenclature occurring in a dataset of any size.As a demonstration, a 105+ Megabyte corpus of Pubmed abstracts was searched for medical terms. Query terms were matched against either of two vocabularies and expanded as an array of equivalent search items. A single search term may have over one hundred nomenclature synonyms, all of which were searched against the full database. Iterative searches of a list of concept-equivalent terms involves many more operations than a single search over pre-annotated concept codes. Nonetheless, the doublet method achieved fast query response times (0.05 seconds using Snomed and 5 seconds using the Developmental Lineage Classification of Neoplasms, on a computer with a 2.89 GHz processor).Pre-annotated datasets lose their value when the chosen vocabulary is replaced by a different vocabulary or by a different version of the same vocabulary. The doublet method can employ any version of any vocabulary with no pre-annotation. In many instances, the enormous effort and expense associated with data annotation can be eliminated by on-the-fly doublet matching.The algorithm for nomenclature-based database searches using the doublet method is described. Perl scripts for implementing the algorithm and testing execution speed are provided as open source documents available from the Association for Pathology Informatics (www.pathologyinformatics.org/informatics_r.htm). JF - In Silico Biology AU - Berman, Jules J AD - Cancer Diagnosis Program, National Cancer Insititute, National Institutes of Health, Bethesda, MD, USA. E-mail: bermanj[at]mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 313 EP - 322 PB - IOS Press, Nieuwe Hemweg 6B VL - 5 IS - 3 SN - 1386-6338, 1386-6338 KW - Biotechnology and Bioengineering Abstracts KW - Nomenclature KW - Integration KW - Databases KW - Data processing KW - Classification KW - medical records KW - Computers KW - Algorithms KW - Cancer KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19552158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=In+Silico+Biology&rft.atitle=Nomenclature-Based+Data+Retrieval+without+Prior+Annotation%3A+Facilitating+Biomedical+Data+Integration+with+Fast+Doublet+Matching&rft.au=Berman%2C+Jules+J&rft.aulast=Berman&rft.aufirst=Jules&rft.date=2005-01-01&rft.volume=5&rft.issue=3&rft.spage=313&rft.isbn=&rft.btitle=&rft.title=In+Silico+Biology&rft.issn=13866338&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-01-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Data processing; Nomenclature; Algorithms; medical records; Databases; Classification; Computers; Cancer; Integration ER - TY - JOUR T1 - The promise and potential challenges of intermittent preventive treatment for malaria in infants (IPTi) AN - 19503579; 7198637 AB - Intermittent preventive treatment (IPT) administers a full therapeutic course of an anti-malarial drug at predetermined intervals, regardless of infection or disease status. It is recommended by the World Health Organization (WHO) for protecting pregnant women from the adverse effects of malaria (IPTp) and shows great potential as a strategy for reducing illness from malaria during infancy (IPTi). Administered concurrently with standard immunizations, IPTi is expected to reduce the frequency of clinical disease, but to allow blood-stage infections to occur between treatments, thus allowing parasite-specific immunity to develop. While wide deployment of IPTi is being considered, it is important to assess other potential effects. Transmission conditions, drug choice and administration schedule will likely affect the possibility of post-treatment rebound in child morbidity and mortality and the increased spread of parasite drug resistance and should be considered when implementing IPTi. JF - Malaria Journal AU - O'Meara, Wendy Prudhomme AU - Breman, Joel G AU - McKenzie, F Ellis AD - Division of Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, MD 20892 USA Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 4 SN - 1475-2875, 1475-2875 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Health & Safety Science Abstracts KW - Article No. 33 KW - Mortality KW - Parasites KW - Drug resistance KW - Malaria KW - Immunity KW - Infection KW - Morbidity KW - Immunization KW - Pregnancy KW - immunization KW - malaria KW - infection KW - Drugs KW - Side effects KW - Infants KW - H 11000:Diseases/Injuries/Trauma KW - K 03400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19503579?accountid=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=Malaria+Journal&rft.atitle=The+promise+and+potential+challenges+of+intermittent+preventive+treatment+for+malaria+in+infants+%28IPTi%29&rft.au=O%27Meara%2C+Wendy+Prudhomme%3BBreman%2C+Joel+G%3BMcKenzie%2C+F+Ellis&rft.aulast=O%27Meara&rft.aufirst=Wendy&rft.date=2005-01-01&rft.volume=4&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Malaria+Journal&rft.issn=14752875&rft_id=info:doi/10.1186%2F1475-2875-4-33 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Parasites; Mortality; Drug resistance; Malaria; Immunity; Infection; Immunization; Morbidity; Side effects; Pregnancy; Infants; immunization; malaria; infection; Drugs DO - http://dx.doi.org/10.1186/1475-2875-4-33 ER - TY - JOUR T1 - Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines AN - 19501433; 7198659 AB - Background: Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi), stimulating this re- analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP) vaccines. Methods In 1975, six villages divided into two groups of children 0.05). The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05) and 77% and 91% for tetanus toxoid (P > 0.05). In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05). While analysis for pertussis showed a 43% (CH+) and 67% (CH-) response (P < 0.05), analyses using logistic regression to control for sex, age, chemoprophylaxis, weight-for-height Z-score, and pre-vaccination geometric mean titer (GMT), demonstrated that chemoprophylaxis was not associated with a significantly different conversion rate following DTP and measles vaccines. Seven months of chemoprophylaxis decreased significantly the malaria IFA and ELISA GMTs in the CH+ group. Conclusion Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine. JF - Malaria Journal AU - Rosen, Jennifer B AU - Breman, Joel G AU - Manclark, Charles R AU - Meade, Bruce D AU - Collins, William E AU - Lobel, Hans O AU - Saliou, Pierre AU - Roberts, Jacquelin M AU - Campaore, Pierre AU - Miller, Mark A AD - Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 4 SN - 1475-2875, 1475-2875 KW - Virology & AIDS Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology; Microbiology Abstracts B: Bacteriology KW - Article No. 53 KW - Pertussis KW - Amodiaquine KW - Enzyme-linked immunosorbent assay KW - Data processing KW - Measles KW - Malaria KW - Toxoids KW - Diphtheria KW - Antibody response KW - Children KW - Tetanus KW - Immunogenicity KW - Seroconversion KW - Vaccines KW - Salmonella KW - Drugs KW - K 03350:Immunology KW - V 22350:Immunology KW - J 02350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19501433?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Malaria+Journal&rft.atitle=Malaria+chemoprophylaxis+and+the+serologic+response+to+measles+and+diphtheria-tetanus-whole-cell+pertussis+vaccines&rft.au=Rosen%2C+Jennifer+B%3BBreman%2C+Joel+G%3BManclark%2C+Charles+R%3BMeade%2C+Bruce+D%3BCollins%2C+William+E%3BLobel%2C+Hans+O%3BSaliou%2C+Pierre%3BRoberts%2C+Jacquelin+M%3BCampaore%2C+Pierre%3BMiller%2C+Mark+A&rft.aulast=Rosen&rft.aufirst=Jennifer&rft.date=2005-01-01&rft.volume=4&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Malaria+Journal&rft.issn=14752875&rft_id=info:doi/10.1186%2F1475-2875-4-53 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Pertussis; Enzyme-linked immunosorbent assay; Amodiaquine; Data processing; Measles; Malaria; Antibody response; Diphtheria; Toxoids; Tetanus; Children; Immunogenicity; Seroconversion; Vaccines; Drugs; Salmonella DO - http://dx.doi.org/10.1186/1475-2875-4-53 ER - TY - JOUR T1 - Social contracts and precautions activate different neurological systems: An fMRI investigation of deontic reasoning AN - 19456173; 6968256 AB - We conducted an event-related, functional MRI investigation of 12 male's and 12 female's reasoning about conditional deontic rules, rules regulating people's behavior. We employed two different types of rules: social contracts and nonsocial, precautionary rules. Although the rules and the demands of the task were matched in terms of their logical structure, reasoning about social contracts and precautions activated a different constellation of neurological structures. The regions differentially activated by social contracts included dorsomedial PFC (BA 6/8), bilateral ventrolateral PFC (BA 47), the left angular gyrus (BA 39), and left orbitofrontal cortex (BA 10). The regions differentially activated by precautions included bilateral insula, the left lentiform nucleus, posterior cingulate (BA 29/31), anterior cingulate (BA 24) and right postcentral gyrus (BA 3). Collectively, reasoning about prescriptive rules activated the dorsomedial PFC (BA 6/8). The results reinforce the view that human reasoning is not a unified phenomenon, but is content-sensitive. JF - NeuroImage AU - Fiddick, Laurence AU - Spampinato, Maria Vittoria AU - Grafman, Jordan AD - Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, Building 10, Room 5C205MSC 1440 Bethesda, MD 20892-1440, United States, grafmanj@ninds.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 778 EP - 786 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 28 IS - 4 SN - 1053-8119, 1053-8119 KW - CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - Lentiform nucleus KW - Cortex KW - Functional magnetic resonance imaging KW - postcentral gyrus KW - Cortex (cingulate) KW - Social interactions KW - W 30910:Imaging KW - N3 11001:Behavioral and Cognitive Neuroscience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19456173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NeuroImage&rft.atitle=Social+contracts+and+precautions+activate+different+neurological+systems%3A+An+fMRI+investigation+of+deontic+reasoning&rft.au=Fiddick%2C+Laurence%3BSpampinato%2C+Maria+Vittoria%3BGrafman%2C+Jordan&rft.aulast=Fiddick&rft.aufirst=Laurence&rft.date=2005-01-01&rft.volume=28&rft.issue=4&rft.spage=778&rft.isbn=&rft.btitle=&rft.title=NeuroImage&rft.issn=10538119&rft_id=info:doi/10.1016%2Fj.neuroimage.2005.05.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Functional magnetic resonance imaging; postcentral gyrus; Lentiform nucleus; Social interactions; Cortex (cingulate); Cortex DO - http://dx.doi.org/10.1016/j.neuroimage.2005.05.033 ER - TY - JOUR T1 - Task-relevant modulation of primary somatosensory cortex suggests a prefrontal-cortical sensory gating system AN - 19452273; 6965374 AB - Increasing evidence suggests that somatosensory information is modulated cortically for task-specific sensory inflow: Several studies report short-term adaptation of representational maps in primary somatosensory cortex (SI) due to attention or induced by task-related motor activity such as handwriting. Recently, it has been hypothesized that the frontal or prefrontal cortex may modulate SI. In order to test this hypothesis, we studied the functional organization of SI while subjects performed the Tower of Hanoi task. This task is known to be related to activation of frontal or prefrontal areas. The functional organization of SI while performing the Tower of Hanoi task was compared to the organization of SI during performing the same movements but without the Tower of Hanoi task and with rest. Topography of SI was assessed using neuromagnetic source imaging based on tactile stimulation of the first (D1) and fifth digits (D5). Performing the Tower of Hanoi task was accompanied by plastic changes in SI as indicated by significant shifts in the cortical representations of D1 and D5: They moved further apart during the Tower of Hanoi task compared to the control task containing the same movements but without the cognitive characteristic. Thus, we conclude that SI maps undergo dynamic modulation depending on motor tasks with different cognitive demands. The results suggest that this short-term plasticity may be regulated by a prefrontal-cortical sensory gating system. JF - NeuroImage AU - Schaefer, Michael AU - Heinze, Hans-Jochen AU - Rotte, Michael AD - Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5N234, Bethesda, MD 20892, USA, schaefem@ninds.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 130 EP - 135 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 27 IS - 1 SN - 1053-8119, 1053-8119 KW - CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - Neuroimaging KW - Plasticity KW - Maps KW - Neuromodulation KW - Cortex KW - Motor activity KW - Functional morphology KW - Topography KW - Adaptations KW - Cognitive ability KW - Gating KW - Tactile stimuli KW - Cortex (prefrontal) KW - Cortex (somatosensory) KW - W 30910:Imaging KW - N3 11001:Behavioral and Cognitive Neuroscience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19452273?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NeuroImage&rft.atitle=Task-relevant+modulation+of+primary+somatosensory+cortex+suggests+a+prefrontal-cortical+sensory+gating+system&rft.au=Schaefer%2C+Michael%3BHeinze%2C+Hans-Jochen%3BRotte%2C+Michael&rft.aulast=Schaefer&rft.aufirst=Michael&rft.date=2005-01-01&rft.volume=27&rft.issue=1&rft.spage=130&rft.isbn=&rft.btitle=&rft.title=NeuroImage&rft.issn=10538119&rft_id=info:doi/10.1016%2Fj.neuroimage.2005.04.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Maps; Functional morphology; Cortex (somatosensory); Cognitive ability; Neuromodulation; Gating; Topography; Motor activity; Neuroimaging; Cortex (prefrontal); Plasticity; Cortex; Adaptations; Tactile stimuli DO - http://dx.doi.org/10.1016/j.neuroimage.2005.04.005 ER - TY - JOUR T1 - Differential effects of paroxetine on raphe and cortical 5-HT sub(1A) binding: A PET study in monkeys AN - 19452195; 6968227 AB - Positron emission tomography (PET) ligands that are sensitive to transient changes in serotonin (5-HT) concentration are desirable for studies of neuropsychiatric diseases. Few studies, however, have sought to demonstrate that variations in 5-HT concentration can be closely tracked with available serotonergic ligands. Microdialysis studies in rats have shown a maximal increase in 5-HT concentration in raphe nuclei after systemic infusion of selective serotonergic re-uptake inhibitors (SSRIs). We performed PET scans with [ super(18)F]FPWAY, an intermediate-affinity antagonist of 5-HT sub(1A) receptors, in 4 anesthetized rhesus monkeys in control studies and after systemic paroxetine administration (5 mg/kg, i.v.). In addition, a paired [ super(11)C]DASB study revealed that this paroxetine regimen produced an occupancy of 54-83% of the serotonin transporters. According to the conventional receptor competition model, increased 5-HT concentration produces decreased binding of the radioactive ligand. Over a 3-h period following paroxetine infusion, a progressively increasing reduction (ranging from 8 +/- 6% to 27 +/- 10%) of [ super(18)F]FPWAY-specific binding was found in the raphe nuclei. This result is interpreted as an SSRI-induced increase in 5-HT concentration, potentially combined with reduced binding to internalized 5-HT sub(1A) receptors. In addition, a transient (1 h) increase in cerebral cortical binding was observed, attributed primarily to a reduction in cortical 5-HT due to the effects of raphe autoreceptor inhibition. This study is the first demonstration of the feasibility of quantifying dynamic changes in 5-HT neurotransmission in the raphe and the cortex with PET. These results lend promise to the use of these serotonergic neuroimaging techniques to study neuropsychiatric disorders. JF - NeuroImage AU - Giovacchini, Giampiero AU - Lang, Lixin AU - Ma, Ying AU - Herscovitch, Peter AU - Eckelman, William C AU - Carson, Richard E AD - PET Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA, richard.e.carson@yale.edu Y1 - 2005 PY - 2005 DA - 2005 SP - 238 EP - 248 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 28 IS - 1 SN - 1053-8119, 1053-8119 KW - CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - Neuroimaging KW - Microdialysis KW - Mental disorders KW - Cortex KW - Neurotransmission KW - Serotonin S1 receptors KW - Positron emission tomography KW - Macaca mulatta KW - Competition KW - Raphe nuclei KW - Serotonin uptake inhibitors KW - Serotonin KW - paroxetine KW - Serotonin transporter KW - W 30910:Imaging KW - N3 11001:Behavioral and Cognitive Neuroscience UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19452195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NeuroImage&rft.atitle=Differential+effects+of+paroxetine+on+raphe+and+cortical+5-HT+sub%281A%29+binding%3A+A+PET+study+in+monkeys&rft.au=Giovacchini%2C+Giampiero%3BLang%2C+Lixin%3BMa%2C+Ying%3BHerscovitch%2C+Peter%3BEckelman%2C+William+C%3BCarson%2C+Richard+E&rft.aulast=Giovacchini&rft.aufirst=Giampiero&rft.date=2005-01-01&rft.volume=28&rft.issue=1&rft.spage=238&rft.isbn=&rft.btitle=&rft.title=NeuroImage&rft.issn=10538119&rft_id=info:doi/10.1016%2Fj.neuroimage.2005.05.042 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Macaca mulatta; Positron emission tomography; paroxetine; Cortex; Serotonin S1 receptors; Mental disorders; Raphe nuclei; Serotonin uptake inhibitors; Microdialysis; Neuroimaging; Competition; Serotonin transporter; Neurotransmission; Serotonin DO - http://dx.doi.org/10.1016/j.neuroimage.2005.05.042 ER - TY - JOUR T1 - The effect of stimulus duty cycle and "off" duration on BOLD response linearity AN - 19450880; 6965369 AB - An ongoing question in functional MRI is precisely how measured signal changes relate to neuronal activity. While this question has been probed using animal models and electrophysiologic measures of neuronal activity, it has also been probed by examining, in humans, the spatial location, magnitude, and temporal dynamics of signal changes to well understood stimuli. With regard to dynamics, several earlier studies have revealed a larger than expected response to brief stimuli, hypothesized to result from nonlinearities in either the hemodynamics or the neuronal activity. In this study, we investigate the linearity of the increase in blood oxygenation level dependent (BOLD) contrast as a function of stimulus duty cycle, as well as the linearity of the decrease in BOLD as a function stimulus "off" duration. These findings not only shed further light on the mechanisms behind BOLD contrast but also give practical information as to what to keep in mind when performing and interpreting event related fMRI experiments. These experiments demonstrated: a) the BOLD signal decrease, on stimulus cessation, was smaller than predicted by a linear system - opposite to what has been reported in the literature associated with a signal increase, and b) the deconvolved event-related BOLD signal is highly dependent on duty cycle (the fraction of time activated vs. non-activated), Several potential mechanisms explaining these dynamics are discussed and modeled. We find that the experimental results are most consistent with a nonlinear neuronal response, but do not rule out significant effects of nonlinear hemodynamic factors, in particular the nonlinear relationship between oxygen extraction fraction and blood flow. JF - NeuroImage AU - Birn, Rasmus M AU - Bandettini, Peter A AD - Laboratory of Brain and Cognition, National Institute of Mental Health, 10 Center Dr., Building 10, Room 1D80, Bethesda, MD 20892-1148, USA, rbirn@nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 70 EP - 82 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 27 IS - 1 SN - 1053-8119, 1053-8119 KW - CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - Functional magnetic resonance imaging KW - Animal models KW - Hemodynamics KW - Oxygen KW - Blood flow KW - nonlinear systems KW - W 30910:Imaging KW - N3 11145:Methodology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19450880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NeuroImage&rft.atitle=The+effect+of+stimulus+duty+cycle+and+%22off%22+duration+on+BOLD+response+linearity&rft.au=Birn%2C+Rasmus+M%3BBandettini%2C+Peter+A&rft.aulast=Birn&rft.aufirst=Rasmus&rft.date=2005-01-01&rft.volume=27&rft.issue=1&rft.spage=70&rft.isbn=&rft.btitle=&rft.title=NeuroImage&rft.issn=10538119&rft_id=info:doi/10.1016%2Fj.neuroimage.2005.03.040 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Functional magnetic resonance imaging; Hemodynamics; Animal models; Oxygen; nonlinear systems; Blood flow DO - http://dx.doi.org/10.1016/j.neuroimage.2005.03.040 ER - TY - JOUR T1 - Head motion suppression using real-time feedback of motion information and its effects on task performance in fMRI AN - 19450310; 6965377 AB - A voluntary head motion suppression method using feedback to subjects of their own head motion information is demonstrated. A real-time fMRI system was developed on standard MR imaging hardware for this purpose. The head motion information was simplified as a four-way arrow display that changed color from green to red when a composite head motion index went beyond a specified threshold. The arrow indicators were integrated into a version of the commonly used visual N-BACK task. Results suggest a significant suppression of head motion consistently in all subjects while the influence on task performance and brain activation was minimal. It is proposed that under certain experimental conditions, voluntary head motion suppression may feasibly be employed without significant compromise of fMRI data. JF - NeuroImage AU - Yang, Shaolin AU - Ross, Thomas J AU - Zhang, Yanqiong AU - Stein, Elliot A AU - Yang, Yihong AD - Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Room 383, Baltimore, MD 21224, USA, yihongyang@intra.nida.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 153 EP - 162 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 27 IS - 1 SN - 1053-8119, 1053-8119 KW - CSA Neurosciences Abstracts; Biotechnology and Bioengineering Abstracts KW - Head KW - Functional magnetic resonance imaging KW - Magnetic resonance imaging KW - Brain KW - Color KW - Feedback KW - W 30910:Imaging KW - N3 11145:Methodology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19450310?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NeuroImage&rft.atitle=Head+motion+suppression+using+real-time+feedback+of+motion+information+and+its+effects+on+task+performance+in+fMRI&rft.au=Yang%2C+Shaolin%3BRoss%2C+Thomas+J%3BZhang%2C+Yanqiong%3BStein%2C+Elliot+A%3BYang%2C+Yihong&rft.aulast=Yang&rft.aufirst=Shaolin&rft.date=2005-01-01&rft.volume=27&rft.issue=1&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=NeuroImage&rft.issn=10538119&rft_id=info:doi/10.1016%2Fj.neuroimage.2005.02.050 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Head; Functional magnetic resonance imaging; Feedback; Magnetic resonance imaging; Brain; Color DO - http://dx.doi.org/10.1016/j.neuroimage.2005.02.050 ER - TY - JOUR T1 - Importance of the surface area ratio on cytokines production by human monocytes in vitro induced by various hydroxyapatite particles AN - 19445213; 6967126 AB - A possible complication associated with the implantation of hydroxyapatite (HA)-based prosthesis is the release of particles. Those particles can be phagocyted by monocytes that are among the first cells to colonize the inflammatory site. The activated monocytes produce inflammatory mediators, such as cytokines, which cause osteoclasts activation. It has previously been demonstrated using a surface area ratio (ratio of the total surface of the given particles to the surface area of cells) of 1 to 1 that there was a correlation between the expression and production of cytokines induced by HA. The present work studies the effect of physical characteristics of HA particles on the production of various inflammatory cytokines (tumour necrosis factor-alpha, interleukin (IL)-6, and IL-8) and anti-inflammatory cytokine (IL-10). However, the experiments were performed using a surface area ratio of 10 to 1. Our data demonstrate that all the particles, whatever their characteristics, induced a high expression of cytokines but the production was different, meaning that there was a post-transcriptional regulation. The size and sintering temperature seemed to be a characteristics that were less important compared to the shape; the needle particles appeared to induce the most important production of all the cytokines studied. JF - Biomaterials AU - Grandjean-Laquerriere, Alexia AU - Laquerriere, Patrice AU - Guenounou, Moncef AU - Laurent-Maquin, Dominique AU - Phillips, Terry M AD - Ultramicro Analytical Immunochemistry Resource, Division of Bioengineering and Physical Science, Office of Research Services, National Institutes of Health, Bethesda, MD 20892, USA, patrice.laquerriere@univ-reims.fr Y1 - 2005 PY - 2005 DA - 2005 SP - 2361 EP - 2369 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 26 IS - 15 SN - 0142-9612, 0142-9612 KW - Biotechnology and Bioengineering Abstracts KW - Hydroxyapatite KW - Cytokines KW - Inflammation KW - Physical characteristics KW - Temperature effects KW - Osteoclasts KW - Surface area KW - Interleukin 10 KW - Interleukin 8 KW - Cell activation KW - Biomaterials KW - Monocytes KW - Post-transcription KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19445213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+the+surface+area+ratio+on+cytokines+production+by+human+monocytes+in+vitro+induced+by+various+hydroxyapatite+particles&rft.au=Grandjean-Laquerriere%2C+Alexia%3BLaquerriere%2C+Patrice%3BGuenounou%2C+Moncef%3BLaurent-Maquin%2C+Dominique%3BPhillips%2C+Terry+M&rft.aulast=Grandjean-Laquerriere&rft.aufirst=Alexia&rft.date=2005-01-01&rft.volume=26&rft.issue=15&rft.spage=2361&rft.isbn=&rft.btitle=&rft.title=Biomaterials&rft.issn=01429612&rft_id=info:doi/10.1016%2Fj.biomaterials.2004.07.036 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Temperature effects; Physical characteristics; Surface area; Osteoclasts; Interleukin 8; Interleukin 10; Inflammation; Cell activation; Hydroxyapatite; Biomaterials; Cytokines; Monocytes; Post-transcription DO - http://dx.doi.org/10.1016/j.biomaterials.2004.07.036 ER - TY - JOUR T1 - Linking pathway gene expressions to the growth inhibition response from the National Cancer Institute's anticancer screen and drug mechanism of action AN - 19442951; 6737253 AB - Novel strategies are proposed to quantitatively analyze and relate biological pathways to drug responses using gene expression and small-molecule growth inhibition data (GI sub(50)) derived from the National Cancer Institute's 60 cancer cells (NCI sub(60)). We have annotated groups of drug GI sub(50) responses with pathways defined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta, and functional categories defined by Gene Ontology (GO), through correlations between pathway gene expression patterns and drug GI sub(50) profiles. Drug-gene-pathway relationships may then be utilized to find drug targets or target-specific drugs. Significantly correlated pathways and the gene products involved represent interesting targets for further exploration, whereas drugs that are significantly correlated with only certain pathways are more likely to be target specific. Separate pathway clustering finds that pathways engaged in the same biological process tend to have similar drug correlation patterns. The biological and statistical significances of our method are established by comparison to known small-molecule inhibitor-gene target relationships reported in the literature and by standard randomization procedures. The results of our pathway, gene expression and drug-induced growth inhibition associations, can serve as a basis for proposing testable hypotheses about potential anticancer drugs, their targets, and mechanisms of action. JF - Pharmacogenomics Journal AU - Huang, R AU - Wallqvist, A AU - Thanki, N AU - Covell, D G AD - Developmental Therapeutics Program, Screening Technologies Branch, Laboratory of Computational Technologies, National Cancer Institute-Frederick, BIdg. 1052/235, Frederick, MD 21702, USA, covell@ncifcrf.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 381 EP - 399 VL - 5 IS - 6 SN - 1470-269X, 1470-269X KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Drug metabolism KW - Statistical analysis KW - Antitumor agents KW - Cancer KW - Gene expression KW - Bioinformatics KW - Antitumor activity KW - W 30915:Pharmaceuticals & Vaccines KW - G 07300:Theoretical genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19442951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenomics+Journal&rft.atitle=Linking+pathway+gene+expressions+to+the+growth+inhibition+response+from+the+National+Cancer+Institute%27s+anticancer+screen+and+drug+mechanism+of+action&rft.au=Huang%2C+R%3BWallqvist%2C+A%3BThanki%2C+N%3BCovell%2C+D+G&rft.aulast=Huang&rft.aufirst=R&rft.date=2005-01-01&rft.volume=5&rft.issue=6&rft.spage=381&rft.isbn=&rft.btitle=&rft.title=Pharmacogenomics+Journal&rft.issn=1470269X&rft_id=info:doi/10.1038%2Fsj.tpj.6500331 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-01-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Gene expression; Drug metabolism; Antitumor agents; Cancer; Antitumor activity; Statistical analysis; Bioinformatics DO - http://dx.doi.org/10.1038/sj.tpj.6500331 ER - TY - JOUR T1 - Human promoter genomic composition demonstrates non-random groupings that reflect general cellular function AN - 19421562; 6531675 AB - The purpose of this study is to determine whether or not there exists nonrandom grouping of cis-regulatory elements within gene promoters that can be perceived independent of gene expression data and whether or not there is any correlation between this grouping and the biological function of the gene. Using ProSpector, a web-based promoter search and annotation tool, we have applied an unbiased approach to analyze the transcription factor binding site frequencies of 1400 base pair genomic segments positioned at 1200 base pairs upstream and 200 base pairs downstream of the transcriptional start site of 7298 commonly studied human genes. Partitional clustering of the transcription factor binding site composition within these promoter segments reveals a small number of gene groups that are selectively enriched for gene ontology terms consistent with distinct aspects of cellular function. Significance ranking of the class- determining transcription factor binding sites within these clusters show substantial overlap between the gene ontology terms of the transcriptions factors associated with the binding sites and the gene ontology terms of the regulated genes within each group. Thus, gene sorting by promoter composition alone produces partitions in which the "regulated" and the "regulators" cosegregate into similar functional classes. These findings demonstrate that the transcription factor binding site composition is non-randomly distributed between gene promoters in a manner that reflects and partially defines general gene class function. JF - BMC Bioinformatics AU - McNutt, Markey C AU - Tongbai, Ron AU - Cui, Wenwu AU - Collins, Irene AU - Freebern, Wendy J AU - Montano, Idalia AU - Haggerty, Cynthia M AU - Chandramouli, GVR AU - Gardner, Kevin AD - The Advanced Technology Center, Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, Maryland 20892-4605, USA Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 6 IS - 1 SN - 1471-2105, 1471-2105 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts KW - Article No. 259 KW - Gene expression KW - Promoters KW - Data processing KW - Transcription factors KW - genomics KW - Bioinformatics KW - Base pairs KW - G 07880:Human Genetics KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19421562?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Bioinformatics&rft.atitle=Human+promoter+genomic+composition+demonstrates+non-random+groupings+that+reflect+general+cellular+function&rft.au=McNutt%2C+Markey+C%3BTongbai%2C+Ron%3BCui%2C+Wenwu%3BCollins%2C+Irene%3BFreebern%2C+Wendy+J%3BMontano%2C+Idalia%3BHaggerty%2C+Cynthia+M%3BChandramouli%2C+GVR%3BGardner%2C+Kevin&rft.aulast=McNutt&rft.aufirst=Markey&rft.date=2005-01-01&rft.volume=6&rft.issue=1&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Bioinformatics&rft.issn=14712105&rft_id=info:doi/10.1186%2F1471-2105-6-259 L2 - http://www.biomedcentral.com/1471-2105/6/259 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Gene expression; Promoters; Data processing; Transcription factors; Bioinformatics; genomics; Base pairs DO - http://dx.doi.org/10.1186/1471-2105-6-259 ER - TY - JOUR T1 - Automatic extraction of candidate nomenclature terms using the doublet method AN - 19415472; 6495816 AB - New terminology continuously enters the biomedical literature. How can curators identify new terms that can be added to existing nomenclatures? The most direct method, and one that has served well, involves reading the current literature. The scholarly curator adds new terms as they are encountered. Present-day scholars are severely challenged by the enormous volume of biomedical literature. Curators of medical nomenclatures need computational assistance if they hope to keep their terminologies current. The purpose of this paper is to describe a method of rapidly extracting new, candidate terms from huge volumes of biomedical text. The resulting lists of terms can be quickly reviewed by curators and added to nomenclatures, if appropriate. The candidate term extractor uses a variation of the previously described doublet coding method. The algorithm, which operates on virtually any nomenclature, derives from the observation that most terms within a knowledge domain are composed entirely of word combinations found in other terms from the same knowledge domain. Terms can be expressed as sequences of overlapping word doublets that have more specific meaning than the individual words that compose the term. The algorithm parses through text, finding contiguous sequences of word doublets that are known to occur somewhere in the reference nomenclature. When a sequence of matching word doublets is encountered, it is compared with whole terms already included in the nomenclature. If the doublet sequence is not already in the nomenclature, it is extracted as a candidate new term. Candidate new terms can be reviewed by a curator to determine if they should be added to the nomenclature. An implementation of the algorithm is demonstrated, using a corpus of published abstracts obtained through the National Library of Medicine's PubMed query service and using "The developmental lineage classification and taxonomy of neoplasms" as a reference nomenclature. A 31+ Megabyte corpus of pathology journal abstracts was parsed using the doublet extraction method. This corpus consisted of 4,289 records, each containing an abstract title. The total number of words included in the abstract titles was 50,547. New candidate terms for the nomenclature were automatically extracted from the titles of abstracts in the corpus. Total execution time on a desktop computer with CPU speed of 2.79 GHz was 2 seconds. The resulting output consisted of 313 new candidate terms, each consisting of concatenated doublets found in the reference nomenclature. Human review of the 313 candidate terms yielded a list of 285 terms approved by a curator. A final automatic extraction of duplicate terms yielded a final list of 222 new terms (71% of the original 313 extracted candidate terms) that could be added to the reference nomenclature. The doublet method for automatically extracting candidate nomenclature terms can be used to quickly find new terms from vast amounts of text. The method can be immediately adapted for virtually any text and any nomenclature. An implementation of the algorithm, in the Perl programming language, is provided with this article. JF - BMC Medical Informatics and Decision Making AU - Berman, Jules J AD - Cancer Diagnosis Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 5 IS - 1 SN - 1472-6947, 1472-6947 KW - Biotechnology and Bioengineering Abstracts KW - Article No. 35 KW - Decision making KW - Classification KW - Computers KW - Reviews KW - Algorithms KW - Taxonomy KW - Language KW - Computer applications KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19415472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Medical+Informatics+and+Decision+Making&rft.atitle=Automatic+extraction+of+candidate+nomenclature+terms+using+the+doublet+method&rft.au=Berman%2C+Jules+J&rft.aulast=Berman&rft.aufirst=Jules&rft.date=2005-01-01&rft.volume=5&rft.issue=1&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Medical+Informatics+and+Decision+Making&rft.issn=14726947&rft_id=info:doi/10.1186%2F1472-6947-5-35 L2 - http://www.biomedcentral.com/1472-6947/5/35 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Algorithms; Reviews; Language; Classification; Computers; Decision making; Computer applications; Taxonomy DO - http://dx.doi.org/10.1186/1472-6947-5-35 ER - TY - JOUR T1 - Motion-corrected free-breathing delayed enhancement imaging of myocardial infarction AN - 19410244; 6496272 AB - Following administration of Gd-DTPA, infarcted myocardium exhibits delayed enhancement and can be imaged using an inversion-recovery sequence. A conventional segmented acquisition requires a number of breath-holds to image the heart. Single-shot phase-sensitive inversion-recovery (PSIR) true-FISP may be combined with parallel imaging using SENSE to achieve high spatial resolution. SNR may be improved by averaging multiple motion-corrected images acquired during free breathing. PSIR techniques have demonstrated a number of benefits including consistent contrast and appearance over a relatively wide range of inversion recovery times (TI), improved contrast-to-noise ratio, and consistent size of the enhanced region. Comparison between images acquired using segmented breath-held turbo-FLASH and averaged, motion-corrected, free-breathing true-FISP show excellent agreement of measured CNR and infarct size. In this study, motion correction was implemented using image registration post-processing rather than navigator correction of individual frames. Navigator techniques may be incorporated as well. JF - Magnetic Resonance in Medicine AU - Kellman, Peter AU - Larson, Andrew C AU - Hsu, Li-Yueh AU - Chung, Yiu-Cho AU - Simonetti, Orlando P AU - McVeigh, Elliot R AU - Arai, Andrew E AD - Laboratory of Cardiac Energetics, National Institutes of Health, National Heart, Lung, and Blood Institute, 10 Center Drive, MSC-1061, Building 10, Room B1D416, Bethesda, MD 20892-1061, USA, kellman@nih.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 194 EP - 200 PB - John Wiley & Sons, Ltd. VL - 53 IS - 1 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts KW - Heart KW - Inversion KW - Respiration KW - N.M.R. KW - imaging KW - Myocardial infarction KW - Myocardium KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19410244?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Motion-corrected+free-breathing+delayed+enhancement+imaging+of+myocardial+infarction&rft.au=Kellman%2C+Peter%3BLarson%2C+Andrew+C%3BHsu%2C+Li-Yueh%3BChung%2C+Yiu-Cho%3BSimonetti%2C+Orlando+P%3BMcVeigh%2C+Elliot+R%3BArai%2C+Andrew+E&rft.aulast=Kellman&rft.aufirst=Peter&rft.date=2005-01-01&rft.volume=53&rft.issue=1&rft.spage=194&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20333 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - imaging; N.M.R.; Myocardium; Myocardial infarction; Respiration; Heart; Inversion DO - http://dx.doi.org/10.1002/mrm.20333 ER - TY - JOUR T1 - Recent Developments in Leishmaniasis: Epidemiology, Diagnosis, and Treatment. AN - 1859465524; 15610669 AB - The outbreaks of cutaneous disease caused by Leishmania tropica in Afghan refugees, visceral disease in Sudanese refugees, and cutaneous disease caused by Leishmania major in American forces in Iraq are examples of the large number of cases of leishmaniasis that can result when naive human populations intrude into regions where transmission is endemic. Injections of pentavalent antimony for 20 to 30 days have been the standard treatment for all forms of leishmaniasis, but resistance is growing and antimonials have moderate toxicity. Two major advances in the treatment of visceral leishmaniasis have been made in the past few years. Liposomal amphotericin B cures virtually all patients, with little side effects. Miltefosine is the first oral agent that is effective. For cutaneous disease, alternatives to antimony have been effective in certain regions but have not yet been generally evaluated. JF - Current infectious disease reports 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 - 2005/01// PY - 2005 DA - January 2005 SP - 33 EP - 38 VL - 7 IS - 1 SN - 1523-3847, 1523-3847 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859465524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Recent+Developments+in+Leishmaniasis%3A+Epidemiology%2C+Diagnosis%2C+and+Treatment.&rft.au=Berman%2C+Jonathan&rft.aulast=Berman&rft.aufirst=Jonathan&rft.date=2005-01-01&rft.volume=7&rft.issue=1&rft.spage=33&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 - 2004-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DETERMINING DISEASE CAUSALITY FROM EXPERIMENTAL TOXICOLOGY STUDIES. AN - 1835542561; 18496612 JF - Journal of law and policy AU - Melnick, Ronald L AU - Bucher, John R AD - Ronald L. Melnick is Director of Special Programs, Environmental Toxicology Program (ETP), National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS); John R. Bucher is Deputy Director ETP, NTP/NIEHS. Y1 - 2005 PY - 2005 DA - 2005 SP - 113 EP - 133 VL - 14 IS - 1 SN - 1074-0635, 1074-0635 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1835542561?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+law+and+policy&rft.atitle=DETERMINING+DISEASE+CAUSALITY+FROM+EXPERIMENTAL+TOXICOLOGY+STUDIES.&rft.au=Melnick%2C+Ronald+L%3BBucher%2C+John+R&rft.aulast=Melnick&rft.aufirst=Ronald&rft.date=2005-01-01&rft.volume=14&rft.issue=1&rft.spage=113&rft.isbn=&rft.btitle=&rft.title=Journal+of+law+and+policy&rft.issn=10740635&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2011-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epididymal Sperm Granuloma Induced by Chronic Administration of 2-Methylimidazole in B6C3F sub(1) Mice AN - 17868322; 6248750 AB - Two-year mouse and rat bioassay studies of 2-methylimidazole (2-MI) conducted by the National Toxicology Program revealed that epididymal sperm granuloma(SG)s occurred only in male B6C3F sub(1) mice in a dose-related manner. The present study characterized 2-MI-induced SGs in these epididymides. Groups of 50 male B6C3F sub(1) mice were fed diets containing 0, 625, 1250, or 2500 ppm 2-MI for 105 weeks; the doses were equivalent to average daily doses of approximately 13, 40, or 130 mg/kg. Testes and epididymides were histopathologically reexamined. 2-Methylimidazole increased the incidence of epididymal SGs (0%, 0%, 6%, 12%, respectively). Histologically, most of the SGs exhibited rupture of epididymal ducts with focal aggregations of macrophages in interstitia. Lesions occurred in the proximal caput of the epididymis and/or efferent ducts, not in the corpus and cauda. In the testis, incidences of germinal epithelial atrophy (GEA) increased dose-relatedly (2%, 8%, 16%, 28%, respectively). All mice with epididymal SG developed testicular GEA. The grading scores of testicular GEA tended to be more severe in mice with SGs than those without. No epididymal SG or testicular GEA was observed in 6-month-interim-sacrificed mice. The results imply that 2-year treatment of B6C3F sub(1) mice with 2-MI can induce epididymal SGs, primarily followed by more severe testicular GEA. The potential mechanism of SG induction by 2-MI is discussed. JF - Toxicologic Pathology AU - Tani, Y AU - Foster, P M AU - Sills, R C AU - Chan, P C AU - Peddada, S D AU - Nyska, A AD - Laboratory of Experimental Pathology, Laboratory of Molecular Toxicology, Toxicology Operations Branch, Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, 27709, USA Y1 - 2005 PY - 2005 DA - 2005 SP - 313 EP - 319 VL - 33 IS - 3 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - Macrophages KW - Diets KW - Testes KW - Epididymis KW - Rupture KW - Atrophy KW - Sperm KW - Granuloma KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17868322?accountid=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=Epididymal+Sperm+Granuloma+Induced+by+Chronic+Administration+of+2-Methylimidazole+in+B6C3F+sub%281%29+Mice&rft.au=Tani%2C+Y%3BFoster%2C+P+M%3BSills%2C+R+C%3BChan%2C+P+C%3BPeddada%2C+S+D%3BNyska%2C+A&rft.aulast=Tani&rft.aufirst=Y&rft.date=2005-01-01&rft.volume=33&rft.issue=3&rft.spage=313&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1080%2F01926230590922866 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sperm; Testes; Rupture; Diets; Atrophy; Epididymis; Macrophages; Granuloma DO - http://dx.doi.org/10.1080/01926230590922866 ER - TY - JOUR T1 - Relationship of hepatocellular carcinoma to soya food consumption: A cohort-based, case-control study in Japan AN - 17863803; 6192005 AB - To determine if the risk of hepatocellular carcinoma (HCC) is reduced by consumption of soya foods, we conducted a case-control study within a cohort of Japanese A-bomb survivors. We compared the prediagnosis consumption of isoflavone-rich miso soup and tofu to HCC risk, adjusting for hepatitis B (HBV) and C (HCV) viral infections, the major HCC risk factors in this p JF - International Journal of Cancer AU - Sharp, Gerald B AU - Lagarde, Frederic AU - Mizuno, Terumi AU - Sauvaget, Catherine AU - Fukuhara, Toshiyuki AU - Allen, Naomi AU - Suzuki, Gen AU - Tokuoka, Shoji AD - Department of Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan, gsharp@niaid.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 290 EP - 295 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 115 IS - 2 SN - 0020-7136, 0020-7136 KW - soya KW - Risk Abstracts KW - Food KW - Risk reduction KW - Cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17863803?accountid=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=Relationship+of+hepatocellular+carcinoma+to+soya+food+consumption%3A+A+cohort-based%2C+case-control+study+in+Japan&rft.au=Sharp%2C+Gerald+B%3BLagarde%2C+Frederic%3BMizuno%2C+Terumi%3BSauvaget%2C+Catherine%3BFukuhara%2C+Toshiyuki%3BAllen%2C+Naomi%3BSuzuki%2C+Gen%3BTokuoka%2C+Shoji&rft.aulast=Sharp&rft.aufirst=Gerald&rft.date=2005-01-01&rft.volume=115&rft.issue=2&rft.spage=290&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Food; Cancer; Risk reduction ER - TY - JOUR T1 - Risk factors for Kaposi's sarcoma among HHV-8 seropositive homosexual men with AIDS AN - 17862422; 6192006 AB - Kaposi's sarcoma (KS) is a frequent complication of the acquired immunodeficiency syndrome (AIDS) in homosexual men. Risk factors for developing this malignancy are uncertain, other than immunosuppression and coinfection with human herpesvirus 8 (HHV-8). We therefore examined factors associated with KS in a cross-sectional analysis of 99 cases among 503 HHV-8 seropositive homosexual men with AIDS. Data were collected by computer-assisted personal interviews and medical chart reviews. HHV-8 seroreactivity was determined by enzyme-linked immunosorbent assay for antibodies against HHV-8 K8.1 glycoprotein. KS was significantly less common in blacks compared to whites [risk ratio (RR) = 0.4; 95% CI = 0.2 =0.8] and more common in subjects who had completed college (RR = 1.7; 95% CI = 1.1-2.7) or had annual income greater than $30,000 (RR = 1.5; 95% CI = 1.1-2.2). KS was less common in cigarette smokers (RR = 0.6; 95% CI = 0.5- 0.9) and users of crack cocaine (RR = 0.4; 95% CI = 0.1-0.8). KS was less common in bisexual men compared to men who were exclusively homosexual (estimated RR = 0.6; 95% CI = 0.4-0.9) and inversely associated with number of female partners. KS was also less common in men who had received pay for sex (RR = 0.6; 95% CI = 0.4-1.0). These cross-sectional associations could be biased by potential differences in relative timing of HHV-8 and HIV infection, a postulated determinant of KS risk. Alternatively, our findings may reflect factors protective against KS in individuals infected with HHV-8. Future research should focus on identifying practical measures for countering KS that do not increase the risk of other diseases. Published 2005 Wiley-Liss, Inc. JF - International Journal of Cancer AU - Nawar, Eric AU - Mbulaiteye, Sam M AU - Gallant, Joel E AU - Wohl, David A AU - Ardini, Marianne AU - Hendershot, Tabitha AU - Goedert, James J AU - Rabkin, Charles S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA, rabkinc@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 296 EP - 300 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 115 IS - 2 SN - 0020-7136, 0020-7136 KW - HIV KW - Kaposi's sarcoma KW - Risk Abstracts; Virology & AIDS Abstracts KW - human herpesvirus KW - AIDS-related malignancy KW - Enzyme-linked immunosorbent assay KW - Acquired immune deficiency syndrome KW - Cigarettes KW - Human herpesvirus 8 KW - Immunodeficiency KW - Homosexuality KW - Drug abuse KW - Antibodies KW - Malignancy KW - Human immunodeficiency virus KW - Bisexuality KW - Reviews KW - Risk factors KW - Bisexual KW - Glycoproteins KW - Cocaine KW - Immunosuppression KW - V 22006:AIDS: Other aspects KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17862422?accountid=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=Risk+factors+for+Kaposi%27s+sarcoma+among+HHV-8+seropositive+homosexual+men+with+AIDS&rft.au=Nawar%2C+Eric%3BMbulaiteye%2C+Sam+M%3BGallant%2C+Joel+E%3BWohl%2C+David+A%3BArdini%2C+Marianne%3BHendershot%2C+Tabitha%3BGoedert%2C+James+J%3BRabkin%2C+Charles+S&rft.aulast=Nawar&rft.aufirst=Eric&rft.date=2005-01-01&rft.volume=115&rft.issue=2&rft.spage=296&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.20887 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Acquired immune deficiency syndrome; Enzyme-linked immunosorbent assay; Cigarettes; Immunodeficiency; Homosexuality; Malignancy; Antibodies; Kaposi's sarcoma; Risk factors; Reviews; Bisexual; Glycoproteins; Cocaine; Immunosuppression; Bisexuality; Drug abuse; Human immunodeficiency virus; Human herpesvirus 8 DO - http://dx.doi.org/10.1002/ijc.20887 ER - TY - JOUR T1 - Comparative Immunogenicity of Human Immunodeficiency Virus Particles and Corresponding Polypeptides in a DNA Vaccine AN - 17862409; 6174058 AB - The immunogenicity of a plasmid DNA expression vector encoding both Gag and envelope (Env), which produced human immunodeficiency virus (HIV) type 1 virus- like particles (VLP), was compared to vectors expressing Gag and Env individually, which presented the same gene products as polypeptides. Vaccination with plasmids that generated VLP showed cellular immunity comparable to that of Gag and cell-mediated or humoral responses similar to those of Env as immunization with separate vectors. These data suggest that DNA vaccines encoding separated HIV polypeptides generate immune responses similar to those generated by viral particles. JF - Journal of Virology AU - Akahata, Wataru AU - Yang, Zhi-Yong AU - Nabel, Gary J AD - Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, Maryland Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - 626 EP - 631 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 79 IS - 1 SN - 0022-538X, 0022-538X KW - HIV-1 KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Expression vectors KW - Envelopes KW - DNA vaccines KW - Human immunodeficiency virus 1 KW - Plasmids KW - Vaccination KW - Immunity (cell-mediated) KW - Immunogenicity KW - N 14025:RNA/DNA role in infection & immune response KW - W3 33345:DNA vaccines KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews KW - F 06104:Virus UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17862409?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Comparative+Immunogenicity+of+Human+Immunodeficiency+Virus+Particles+and+Corresponding+Polypeptides+in+a+DNA+Vaccine&rft.au=Akahata%2C+Wataru%3BYang%2C+Zhi-Yong%3BNabel%2C+Gary+J&rft.aulast=Akahata&rft.aufirst=Wataru&rft.date=2005-01-01&rft.volume=79&rft.issue=1&rft.spage=626&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Expression vectors; DNA vaccines; Immunogenicity; Envelopes; Vaccination; Immunity (cell-mediated); Plasmids ER - TY - JOUR T1 - Comparative Efficacy and Immunogenicity of Replication-Defective, Recombinant Glycoprotein, and DNA Vaccines for Herpes Simplex Virus 2 Infections in Mice and Guinea Pigs AN - 17861586; 6173486 AB - Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. dl5-29 was also effective in treating established infections. Moreover, latent dl5-29 virus could not be detected by PCR in sacral ganglia from guinea pigs vaccinated intravaginally. Finally, dl5- 29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8 super(+) T cells in trigeminal ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8 super(+)-T-cell responses, the dl5-29 vaccine may be a good candidate for early-phase human trials. JF - Journal of Virology AU - Hoshino, Yo AU - Dalai, Sarat K AU - Wang, Kening AU - Pesnicak, Lesley AU - Lau, Tsz Y AU - Knipe, David M AU - Cohen, Jeffrey I AU - Straus, Stephen E AD - Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - 410 EP - 418 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 79 IS - 1 SN - 0022-538X, 0022-538X KW - mice KW - guinea pigs KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - DNA vaccines KW - Lymphocytes T KW - Glycoproteins KW - CD8 antigen KW - Plasmids KW - Lipid A KW - Vaccines KW - glycoprotein D KW - Herpes simplex virus 1 KW - Trigeminal ganglion KW - Herpes simplex virus 2 KW - Sacrum KW - Genital diseases KW - Ganglia KW - W3 33365:Vaccines (other) KW - N 14025:RNA/DNA role in infection & immune response KW - V 22097:Immunization: Vaccines & vaccination: Human KW - V 22150:Animal models & experimentally-induced viral infections KW - F 06100:Vaccines - active immunity KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17861586?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Comparative+Efficacy+and+Immunogenicity+of+Replication-Defective%2C+Recombinant+Glycoprotein%2C+and+DNA+Vaccines+for+Herpes+Simplex+Virus+2+Infections+in+Mice+and+Guinea+Pigs&rft.au=Hoshino%2C+Yo%3BDalai%2C+Sarat+K%3BWang%2C+Kening%3BPesnicak%2C+Lesley%3BLau%2C+Tsz+Y%3BKnipe%2C+David+M%3BCohen%2C+Jeffrey+I%3BStraus%2C+Stephen+E&rft.aulast=Hoshino&rft.aufirst=Yo&rft.date=2005-01-01&rft.volume=79&rft.issue=1&rft.spage=410&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Herpes simplex virus 2; Herpes simplex virus 1; Vaccines; Plasmids; Lipid A; Glycoproteins; Sacrum; Lymphocytes T; Ganglia; CD8 antigen; Trigeminal ganglion; Genital diseases; glycoprotein D; DNA vaccines ER - TY - JOUR T1 - Toenail selenium and risk of hepatocellular carcinoma mortality in Haimen City, China AN - 17859957; 6207391 AB - Selenium (Se) is an essential trace mineral with known anticarcinogenic properties in humans. However, few studies have examined the association between Se nutrient status and risk of liver cancer. We conducted a nested case-control study comparing the Se content in toenail clippings of 166 individuals (154 men, 12 women) with hepatocellular carcinoma (HCC) to 394 healthy controls (360 men, 34 women) in Haimen City, China, where HCC is a leading cause of mortality. Toenail Se concentration was measured by inductively coupled plasma-optical emission spectroscopy. Median toenail Se was lower for HCC cases than controls (p = 0.03). Adjusted odds ratios and 95% confidence intervals for HCC mortality by increasing quartile of toenail Se were 1.00 (reference), 0.58 (0.32-1.03), 0.83 (0.48-1.42) and 0.50 (0.28-0.90), with a marginally significant trend in risk observed (p for trend = 0.06). This inverse association appeared stronger among those who did not consume alcohol and among women. Future studies are needed to examine the interrelationship between Se, viral hepatitis infection and HCC in order to better understand the etiologic mechanisms involved and evaluate the true chemopreventive potential of Se compounds for liver diseases. JF - International Journal of Cancer AU - Sakoda, Lori C AU - Graubard, Barry I AU - Evans, Alison A AU - London, WThomas AU - Lin, Wen-Yao AU - Shen, Fu-Min AU - McGlynn, Katherine A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA, sakodal@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 618 EP - 624 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 115 IS - 4 SN - 0020-7136, 0020-7136 KW - hepatocellular carcinoma KW - Risk Abstracts; Toxicology Abstracts KW - Toenail KW - Bioindicators KW - Mortality KW - Liver diseases KW - Liver cancer KW - Nutrients KW - Infection KW - Spectroscopy KW - Cancer KW - Selenium KW - alcohols KW - Minerals KW - Nutrient status KW - Hepatocellular carcinoma KW - X 24166:Environmental impact KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17859957?accountid=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=Toenail+selenium+and+risk+of+hepatocellular+carcinoma+mortality+in+Haimen+City%2C+China&rft.au=Sakoda%2C+Lori+C%3BGraubard%2C+Barry+I%3BEvans%2C+Alison+A%3BLondon%2C+WThomas%3BLin%2C+Wen-Yao%3BShen%2C+Fu-Min%3BMcGlynn%2C+Katherine+A&rft.aulast=Sakoda&rft.aufirst=Lori&rft.date=2005-01-01&rft.volume=115&rft.issue=4&rft.spage=618&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.20937 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mortality; Selenium; Nutrients; Bioindicators; Cancer; Toenail; Hepatocellular carcinoma; Nutrient status; Liver diseases; alcohols; Spectroscopy; Liver cancer; Infection; Minerals DO - http://dx.doi.org/10.1002/ijc.20937 ER - TY - JOUR T1 - Oxygen, Metabolism, and Gene Expression: The T-Rex Connection AN - 17852597; 6138222 AB - In this issue of Structure, Sickmier et al. (2005), report the structure of the redox-sensing repressor from the gram-positive bacterium Thermus aquaticus (T-Rex), a protein that links gene expression to oxygen limitation and the metabolic state of the cell. JF - Structure AU - Wood, MJ AU - Storz, G AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, storz@helix.nih.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 2 EP - 4 PB - Cell Press, 1100 Massachusetts Avenue Cambridge MA 02138 USA, [mailto:subs@cell.com], [URL:http://www.cellpress.com] VL - 13 IS - 1 SN - 0969-2126, 0969-2126 KW - Microbiology Abstracts B: Bacteriology KW - Gene expression KW - Oxygen KW - Thermus aquaticus KW - Repressors KW - Metabolism KW - J 02727:Amino acids, peptides and proteins KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17852597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Structure&rft.atitle=Oxygen%2C+Metabolism%2C+and+Gene+Expression%3A+The+T-Rex+Connection&rft.au=Wood%2C+MJ%3BStorz%2C+G&rft.aulast=Wood&rft.aufirst=MJ&rft.date=2005-01-01&rft.volume=13&rft.issue=1&rft.spage=2&rft.isbn=&rft.btitle=&rft.title=Structure&rft.issn=09692126&rft_id=info:doi/10.1016%2Fj.str.2004.12.002 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Gene expression; Oxygen; Repressors; Metabolism; Thermus aquaticus DO - http://dx.doi.org/10.1016/j.str.2004.12.002 ER - TY - JOUR T1 - Glucose metabolism at high density growth of E. coli B and E. coli K: Differences in metabolic pathways are responsible for efficient glucose utilization in E. coli B as determined by microarrays and Northern blot analyses AN - 17848198; 6248011 AB - In a series of previous reports it was established by implementing metabolic flux, NMR/MS, and Northern blot analysis that the glyoxylate shunt, the TCA cycle, and acetate uptake by acetyl-CoA synthetase are more active in Escherichia coli BL21 than in Escherichia coli JM109. These differences were accepted as the reason for the differences in the glucose metabolism and acetate excretion of these two strains. Examination of the bacterial metabolism by microarrays and time course Northern blot showed that in addition to the glyoxylate shunt, the TCA cycle and the acetate uptake, other metabolic pathways are active differently in the two strains. These are gluconeogenesis, sfcA shunt, ppc shunt, glycogen biosynthesis, and fatty acid degradation. It was found that in E. coli JM109, acetate is produced by pyruvate oxidase (poxB) using pyruvate as a substrate rather than by phosphotransacetylase-acetate kinase (Pta-AckA) system which uses acetyl-CoA. The inactivation of the gluconeogenesis enzyme phosphoenolpyruvate synthetase (ppsA), the activation of the anaplerotic sfcA shunt, and low and stable pyruvate dehydrogenase (aceE, aceF) cause pyruvate accumulation which is converted to acetate by pyruvate oxidase B. The behavior of the ppsA, acs, and aceBAK in JM109 was dependent on the glucose supply strategy. When the glucose concentration was high, no transcription of these genes was observed and acetate concentration increased, but at low glucose concentrations these genes were expressed and the acetate concentration decreased. It is possible that there is a major regulatory molecule that controls not only ppsA and aceBAK but also acs. The gluconeogenesis pathway (fbp, pckA, and ppsA) which leads to glycogen accumulation is constitutively active in E. coli BL21 regardless of glucose feeding strategy. Published 2005 Wiley Periodicals, Inc. JF - Biotechnology and Bioengineering AU - Phue, Je-Nie AU - Noronha, Santosh B AU - Hattacharyya, Ritabrata AU - Wolfe, Alan J AU - Shiloach, Joseph AD - Biotechnology Unit, NIH NIDDK, Bethesda, Maryland 20892-2715, yossi@nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 805 EP - 820 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 90 IS - 7 SN - 0006-3592, 0006-3592 KW - Microbiology Abstracts A: Industrial & Applied Microbiology KW - Escherichia coli KW - acetate KW - glucose KW - Northern blot KW - gluconeogenesis KW - Feeding KW - Biodegradation KW - Glucose KW - Enzymes KW - Transcription KW - Glucose metabolism KW - Acetic acid KW - Glycogen KW - dehydrogenase KW - Pyruvic acid KW - Behavior KW - Shunts KW - Gluconeogenesis KW - Fatty acids KW - Metabolic pathways KW - Excretion KW - N.M.R. KW - Tricarboxylic acid cycle KW - Pyruvate oxidase KW - metabolic flux KW - A 01015:Fermentation & related processes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17848198?accountid=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=Biotechnology+and+Bioengineering&rft.atitle=Glucose+metabolism+at+high+density+growth+of+E.+coli+B+and+E.+coli+K%3A+Differences+in+metabolic+pathways+are+responsible+for+efficient+glucose+utilization+in+E.+coli+B+as+determined+by+microarrays+and+Northern+blot+analyses&rft.au=Phue%2C+Je-Nie%3BNoronha%2C+Santosh+B%3BHattacharyya%2C+Ritabrata%3BWolfe%2C+Alan+J%3BShiloach%2C+Joseph&rft.aulast=Phue&rft.aufirst=Je-Nie&rft.date=2005-01-01&rft.volume=90&rft.issue=7&rft.spage=805&rft.isbn=&rft.btitle=&rft.title=Biotechnology+and+Bioengineering&rft.issn=00063592&rft_id=info:doi/10.1002%2Fbit.20478 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Feeding; Biodegradation; Glucose; Transcription; Enzymes; Glucose metabolism; Acetic acid; dehydrogenase; Glycogen; Pyruvic acid; Behavior; Shunts; Gluconeogenesis; Metabolic pathways; Fatty acids; N.M.R.; Excretion; Tricarboxylic acid cycle; Pyruvate oxidase; metabolic flux; Escherichia coli DO - http://dx.doi.org/10.1002/bit.20478 ER - TY - JOUR T1 - Perceived job stress of women workers in diverse manufacturing industries AN - 17847029; 6247863 AB - An investigation of the impact of organizational factors on perceived job stress among women workers in the IT-dominated garment and electronics industries in the Philippines was undertaken. The sample included 23 establishments with 630 women respondents. Questionnaires, walk-through surveys of the industries, and interviews were done. The workplace factors included the content of the job, the nature of tasks, job autonomy, hazard exposure, and management and supervisory styles. Chi-square analysis showed that there were interactions among the organizational factors (P = 0.05 and 0.10). These factors included the need for better quality and new products; tasks requiring intense concentration; exposure to radiation, chemical, noise, and vapor hazards; standing for prolonged periods of time; and highly monitored, repetitious work. Workers experienced job stress (P = .05) when they were subjected to low job autonomy, poor work quality, close monitoring, and hazardous work pressure. JF - Human Factors and Ergonomics in Manufacturing AU - Lu, Jinky Leilanie AD - Department of Social Sciences, National Institutes of Health and Affiliate- College of Arts and Sciences, University of the Philippines, Manila, jinky_lu@yahoo.com Y1 - 2005 PY - 2005 DA - 2005 SP - 275 EP - 291 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 15 IS - 3 SN - 1090-8471, 1090-8471 KW - Health & Safety Science Abstracts KW - Manufacturing industry KW - Philippines KW - Stress KW - working conditions KW - Vapors KW - Human factors KW - Females KW - Electronics industry KW - Ergonomics KW - Occupational exposure KW - Occupational health KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17847029?accountid=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=Human+Factors+and+Ergonomics+in+Manufacturing&rft.atitle=Perceived+job+stress+of+women+workers+in+diverse+manufacturing+industries&rft.au=Lu%2C+Jinky+Leilanie&rft.aulast=Lu&rft.aufirst=Jinky&rft.date=2005-01-01&rft.volume=15&rft.issue=3&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Human+Factors+and+Ergonomics+in+Manufacturing&rft.issn=10908471&rft_id=info:doi/10.1002%2Fhfm.20026 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Philippines; Occupational exposure; Stress; Females; Electronics industry; Human factors; Vapors; working conditions; Ergonomics; Manufacturing industry; Occupational health DO - http://dx.doi.org/10.1002/hfm.20026 ER - TY - JOUR T1 - Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate AN - 17841568; 6257826 AB - Gestational exposure to di-n-butyl phthalate (DBP), a ubiquitous environmental contaminant, has been shown to interfere with the development of the male reproductive tract by acting as an antiandrogen. This study was conducted to identify the critical days for the abnormal development of the male reproductive tract, specifically the testis and epididymis. Timed-pregnant Sprague-Dawley rats were dosed with DBP at 500 mg/kg/day on gestation day (GD) 14 and 15, 15 and 16, 16 and 17, 17 and 18, 18 and 19, or 19 and 20 (GD 0=plug day). Anogenital distance (AGD) was measured on postnatal day (PND) 1 and 13, while areloa number was recorded on PND 13 only. After weaning, males were allowed to mature to PND 90 at which time they were necropsied. Areloa number and AGD were recorded and testes, epididymides, seminal vesicles, prostate gland, kidneys, and liver weighed. Blood serum was collected and assayed for total testosterone concentration. There were no observable effects on litter size, sex ratio, serum testosterone concentration, or mortality of pups. Statistically significant permanent reductions in AGD were seen in males exposed prenatally to DBP on GD 15 and 16 or GD 18 and 19. On PND 13, areola were present in males exposed to DBP on GD 15 and 16, 16 and 17, 17 and 18, and 19 and 20. However, permanent retention occurred only in males after DBP exposure on GD 16 and 17. Exposure to DBP on only GD 17 and 18 elicited a reduction in epididymal weights; while exposure on only GD 16 and 17 caused a significant increase in the weights of the testes due to edema. In this study, epididymal and testicular malformations were most prevalent after exposure to DBP on any gestational day. Epididymal malformations, characterized by agenesis of various regions and small or flaccid testes were significantly increased in DBP-exposed males only on GD 16 and 17. These findings suggest that 2-day DBP exposure is highly detrimental to the developing reproductive tract of the male fetus and the critical window for abnormal development is GD 16-18. JF - Birth Defects Research Part B: Developmental and Reproductive Toxicology AU - Carruthers, Christina M AU - Foster, Paul MD AD - National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, carruth1@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 277 EP - 285 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 74 IS - 3 SN - 1542-9733, 1542-9733 KW - Toxicology Abstracts KW - Testes KW - Sex ratio KW - Epididymis KW - Statistical analysis KW - Edema KW - Weaning KW - Blood KW - phthalates KW - Testosterone KW - antiandrogens KW - seminal vesicles KW - Glands KW - Gestation KW - Liver KW - Kidney KW - Congenital defects KW - Contaminants KW - Prostate KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17841568?accountid=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=Birth+Defects+Research+Part+B%3A+Developmental+and+Reproductive+Toxicology&rft.atitle=Critical+window+of+male+reproductive+tract+development+in+rats+following+gestational+exposure+to+di-n-butyl+phthalate&rft.au=Carruthers%2C+Christina+M%3BFoster%2C+Paul+MD&rft.aulast=Carruthers&rft.aufirst=Christina&rft.date=2005-01-01&rft.volume=74&rft.issue=3&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Birth+Defects+Research+Part+B%3A+Developmental+and+Reproductive+Toxicology&rft.issn=15429733&rft_id=info:doi/10.1002%2Fbdrb.20050 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Testes; phthalates; Testosterone; Sex ratio; antiandrogens; Gestation; Congenital defects; Contaminants; Weaning; Statistical analysis; seminal vesicles; Kidney; Edema; Prostate; Glands; Epididymis; Liver; Blood DO - http://dx.doi.org/10.1002/bdrb.20050 ER - TY - JOUR T1 - The Salmonella SPI1 effector SopB stimulates nitric oxide production long after invasion AN - 17841085; 6231248 AB - The ability of Salmonella enterica to invade and replicate within host cells depends on two type III secretion systems (TTSSs) encoded on pathogenicity islands 1 and 2 (SPI1 and SPI2). The current paradigm holds that these systems translocate two classes of effectors that operate sequentially and independently. In essence, the SPI1 TTSS mediates early events (i.e. invasion) whereas the SPI2 TTSS mediates post-invasion processes (i.e. replication, vacuole maturation). Contrary to this model, we have found in infected macrophages that a SPI1 effector, SopB-SigD, increased inducible nitric oxide synthase levels and nitric oxide production, host cell process previously known only to be a target of the SPI2 TTSS. Furthermore, SopB protein and message persist many hours after invasion. Our findings reveal an unanticipated potential for dialogue between the SPI1 and SPI2 TTSS and the host cell response. JF - Cellular Microbiology AU - Drecktrah, Dan AU - Knodler, Leigh A AU - Galbraith, Kendal AU - Steele-Mortimer, Olivia AD - Laboratory of Intracellular Parasites, National Institutes of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840, USA, omortimer@niaid.nih.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 105 EP - 113 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 7 IS - 1 SN - 1462-5814, 1462-5814 KW - SigD protein KW - SopB protein KW - secretion system (type III) KW - Microbiology Abstracts B: Bacteriology KW - pathogenicity islands KW - Macrophages KW - Nitric-oxide synthase KW - Replication KW - Salmonella enterica KW - Vacuoles KW - Nitric oxide KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17841085?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+Salmonella+SPI1+effector+SopB+stimulates+nitric+oxide+production+long+after+invasion&rft.au=Drecktrah%2C+Dan%3BKnodler%2C+Leigh+A%3BGalbraith%2C+Kendal%3BSteele-Mortimer%2C+Olivia&rft.aulast=Drecktrah&rft.aufirst=Dan&rft.date=2005-01-01&rft.volume=7&rft.issue=1&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Cellular+Microbiology&rft.issn=14625814&rft_id=info:doi/10.1111%2Fj.1462-5822.2004.00436.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Figures, 6; tables, 1; references, 36. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Salmonella enterica; Nitric oxide; Replication; Vacuoles; Nitric-oxide synthase; Macrophages; pathogenicity islands DO - http://dx.doi.org/10.1111/j.1462-5822.2004.00436.x ER - TY - JOUR T1 - NCBI GEO: mining millions of expression profiles-database and tools AN - 17840806; 6174725 AB - The Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) is the largest fully public repository for high-throughput molecular abundance data, primarily gene expression data. The database has a flexible and open design that allows the submission, storage and retrieval of many data types. These data include microarray-based experiments measuring the abundance of mRNA, genomic DNA and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. GEO currently holds over 30 000 submissions representing approximately half a billion individual molecular abundance measurements, for over 100 organisms. Here, we describe recent database developments that facilitate effective mining and visualization of these data. Features are provided to examine data from both experiment-and gene-centric perspectives using user-friendly Web-based interfaces accessible to those without computational or microarray-related analytical expertise. The GEO database is publicly accessible through the World Wide Web at http://www.ncbi.nlm.nih.gov/geo. JF - Nucleic Acids Research AU - Barrett, Tanya AU - Suzek, Tugba O AU - Troup, Dennis B AU - Wilhite, Stephen E AU - Ngau, Wing-Chi AU - Ledoux, Pierre AU - Rudnev, Dmitry AU - Lash, Alex E AU - Fujibuchi, Wataru AU - Edgar, Ron AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 45 Center Drive, Bethesda, MD, USA Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - D562 EP - D566 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 33 SN - 0305-1048, 0305-1048 KW - Gene expression omnibus KW - NCBI KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Gene expression KW - Databases KW - genomics KW - proteomics KW - DNA microarrays KW - N 14010:Physical & Computer Methods & Assays KW - W 30965:Miscellaneous, Reviews KW - G 07300:Theoretical genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17840806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=NCBI+GEO%3A+mining+millions+of+expression+profiles-database+and+tools&rft.au=Barrett%2C+Tanya%3BSuzek%2C+Tugba+O%3BTroup%2C+Dennis+B%3BWilhite%2C+Stephen+E%3BNgau%2C+Wing-Chi%3BLedoux%2C+Pierre%3BRudnev%2C+Dmitry%3BLash%2C+Alex+E%3BFujibuchi%2C+Wataru%3BEdgar%2C+Ron&rft.aulast=Barrett&rft.aufirst=Tanya&rft.date=2005-01-01&rft.volume=33&rft.issue=&rft.spage=D562&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene expression; proteomics; genomics; DNA microarrays; Databases ER - TY - JOUR T1 - The Molecular Biology Database Collection: 2005 update AN - 17839549; 6174710 AB - The Nucleic Acids Research Molecular Biology Database Collection is a public online resource that lists the databases described in this and previous issues of Nucleic Acids Research together with other databases of value to the biologist and available throughout the world. All databases included in this Collection are freely available to the public. The 2005 update includes 719 databases, 171 more than the 2004 one. The databases are organized in a hierarchical classification that simplifies the process of finding the right database for any given task. The growing number of databases related to immunology, plant and organelle research have been accommodated by separating them into three new categories. The database summaries provide brief descriptions of the databases, contact details, appropriate references and acknowledgements. The online summaries also serve as a venue for the maintainers of each database to introduce database updates and other improvements in the scope and tools. These updates are particularly important for those databases that have not been described in print in the recent past. The database list and summaries are available online at the Nucleic Acids Research web site, http://nar.oupjournals.org/. JF - Nucleic Acids Research AU - Galperin, Michael Y AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - D5 EP - D24 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 33 SN - 0305-1048, 0305-1048 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Databases KW - nucleic acids KW - Classification KW - Collections KW - Organelles KW - N 14100:Reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17839549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=The+Molecular+Biology+Database+Collection%3A+2005+update&rft.au=Galperin%2C+Michael+Y&rft.aulast=Galperin&rft.aufirst=Michael&rft.date=2005-01-01&rft.volume=33&rft.issue=&rft.spage=D5&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Collections; Databases; nucleic acids; Classification; Organelles ER - TY - JOUR T1 - Database resources of the National Center for Biotechnology Information AN - 17839448; 6174685 AB - In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data retrieval systems and computational resources for the analysis of data in GenBank and other biological data made available through NCBI's website. NCBI resources include Entrez, Entrez Programming Utilities, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs), Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD) and the Conserved Domain Architecture Retrieval Tool (CDART). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of the resources can be accessed through the NCBI home page at http://www.ncbi.nlm.nih.gov. JF - Nucleic Acids Research AU - Wheeler, David L AU - Barrett, Tanya AU - Benson, Dennis A AU - Bryant, Stephen H AU - Canese, Kathi AU - Church, Deanna M AU - Dicuccio, Michael AU - Edgar, Ron AU - Federhen, Scott AU - Helmberg, Wolfgang AU - Kenton, David L AU - Khovayko, Oleg AU - Lipman, David J AU - Madden, Thomas L AU - Maglott, Donna R AU - Ostell, James AU - Pontius, Joan U AU - Pruitt, Kim D AU - Schuler, Gregory D AU - Schriml, Lynn M AU - Sequeira, Edwin AU - Sherry, Steven T AU - Sirotkin, Karl AU - Starchenko, Grigory AU - Suzek, Tugba O AU - Tatusov, Roman AU - Tatusova, Tatiana A AU - Wagner, Lukas AU - Yaschenko, Eugene AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A, 8600 Rockville Pike, Bethesda, MD Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - D39 EP - D45 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 33 SN - 0305-1048, 0305-1048 KW - NCBI KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Databases KW - Nucleotide sequence KW - Bioinformatics KW - Biotechnology KW - N 14010:Physical & Computer Methods & Assays KW - W 30965:Miscellaneous, Reviews KW - G 07300:Theoretical genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17839448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Database+resources+of+the+National+Center+for+Biotechnology+Information&rft.au=Wheeler%2C+David+L%3BBarrett%2C+Tanya%3BBenson%2C+Dennis+A%3BBryant%2C+Stephen+H%3BCanese%2C+Kathi%3BChurch%2C+Deanna+M%3BDicuccio%2C+Michael%3BEdgar%2C+Ron%3BFederhen%2C+Scott%3BHelmberg%2C+Wolfgang%3BKenton%2C+David+L%3BKhovayko%2C+Oleg%3BLipman%2C+David+J%3BMadden%2C+Thomas+L%3BMaglott%2C+Donna+R%3BOstell%2C+James%3BPontius%2C+Joan+U%3BPruitt%2C+Kim+D%3BSchuler%2C+Gregory+D%3BSchriml%2C+Lynn+M%3BSequeira%2C+Edwin%3BSherry%2C+Steven+T%3BSirotkin%2C+Karl%3BStarchenko%2C+Grigory%3BSuzek%2C+Tugba+O%3BTatusov%2C+Roman%3BTatusova%2C+Tatiana+A%3BWagner%2C+Lukas%3BYaschenko%2C+Eugene&rft.aulast=Wheeler&rft.aufirst=David&rft.date=2005-01-01&rft.volume=33&rft.issue=&rft.spage=D39&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Databases; Nucleotide sequence; Biotechnology; Bioinformatics ER - TY - JOUR T1 - CDD: a Conserved Domain Database for protein classification AN - 17838919; 6174184 AB - The Conserved Domain Database (CDD) is the protein classification component of NCBI's Entrez query and retrieval system. CDD is linked to other Entrez databases such as Proteins, Taxonomy and PubMed[reg.], and can be accessed at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=cdd. CD-Search, which is available at http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi, is a fast, interactive tool to identify conserved domains in new protein sequences. CD- Search results for protein sequences in Entrez are pre-computed to provide links between proteins and domain models, and computational annotation visible upon request. Protein-protein queries submitted to NCBI's BLAST search service at http://www.ncbi.nlm.nih.gov/BLAST are scanned for the presence of conserved domains by default. While CDD started out as essentially a mirror of publicly available domain alignment collections, such as SMART, Pfam and COG, we have continued an effort to update, and in some cases replace these models with domain hierarchies curated at the NCBI. Here, we report on the progress of the curation effort and associated improvements in the functionality of the CDD information retrieval system. JF - Nucleic Acids Research AU - Marchler-Bauer, Aron AU - Anderson, John B AU - Cherukuri, Praveen F AU - Deweese-Scott, Carol AU - Geer, Lewis Y AU - Gwadz, Marc AU - He, Siqian AU - Hurwitz, David I AU - Jackson, John D AU - Ke, Zhaoxi AU - Lanczycki, Christopher J AU - Liebert, Cynthia A AU - Liu, Chunlei AU - Lu, Fu AU - Marchler, Gabriele H AU - Mullokandov, Mikhail AU - Shoemaker, Benjamin A AU - Simonyan, Vahan AU - Song, James S AU - Thiessen, Paul A AU - Yamashita, Roxanne A AU - Yin, Jodie J AU - Zhang, Dachuan AU - Bryant, Stephen H AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38 A, Room 8N805, 8600 Rockville Pike, Bethesda, MD Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - D192 EP - D196 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 33 SN - 0305-1048, 0305-1048 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Protein structure KW - Databases KW - Information processing KW - Taxonomy KW - proteomics KW - Computer applications KW - N 14010:Physical & Computer Methods & Assays KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17838919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=CDD%3A+a+Conserved+Domain+Database+for+protein+classification&rft.au=Marchler-Bauer%2C+Aron%3BAnderson%2C+John+B%3BCherukuri%2C+Praveen+F%3BDeweese-Scott%2C+Carol%3BGeer%2C+Lewis+Y%3BGwadz%2C+Marc%3BHe%2C+Siqian%3BHurwitz%2C+David+I%3BJackson%2C+John+D%3BKe%2C+Zhaoxi%3BLanczycki%2C+Christopher+J%3BLiebert%2C+Cynthia+A%3BLiu%2C+Chunlei%3BLu%2C+Fu%3BMarchler%2C+Gabriele+H%3BMullokandov%2C+Mikhail%3BShoemaker%2C+Benjamin+A%3BSimonyan%2C+Vahan%3BSong%2C+James+S%3BThiessen%2C+Paul+A%3BYamashita%2C+Roxanne+A%3BYin%2C+Jodie+J%3BZhang%2C+Dachuan%3BBryant%2C+Stephen+H&rft.aulast=Marchler-Bauer&rft.aufirst=Aron&rft.date=2005-01-01&rft.volume=33&rft.issue=&rft.spage=D192&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Protein structure; proteomics; Databases; Taxonomy; Information processing; Computer applications ER - TY - JOUR T1 - NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins AN - 17838049; 6174711 AB - The National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) database (http://www.ncbi.nlm.nih.gov/RefSeq/) provides a non-redundant collection of sequences representing genomic data, transcripts and proteins. Although the goal is to provide a comprehensive dataset representing the complete sequence information for any given species, the database pragmatically includes sequence data that are currently publicly available in the archival databases. The database incorporates data from over 2400 organisms and includes over one million proteins representing significant taxonomic diversity spanning prokaryotes, eukaryotes and viruses. Nucleotide and protein sequences are explicitly linked, and the sequences are linked to other resources including the NCBI Map Viewer and Gene. Sequences are annotated to include coding regions, conserved domains, variation, references, names, database cross-references, and other features using a combined approach of collaboration and other input from the scientific community, automated annotation, propagation from GenBank and curation by NCBI staff. JF - Nucleic Acids Research AU - Pruitt, Kim D AU - Tatusova, Tatiana AU - Maglott, Donna R AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Rm 6An.12J, 45 Center Drive, Bethesda, MD Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - D501 EP - D504 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 33 SN - 0305-1048, 0305-1048 KW - NCBI KW - RefSeq KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Nucleotide sequence KW - Viruses KW - Eukaryotes KW - proteomics KW - Prokaryotes KW - genomics KW - Genetic mapping KW - N 14010:Physical & Computer Methods & Assays KW - W 30965:Miscellaneous, Reviews KW - G 07300:Theoretical genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17838049?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=NCBI+Reference+Sequence+%28RefSeq%29%3A+a+curated+non-redundant+sequence+database+of+genomes%2C+transcripts+and+proteins&rft.au=Pruitt%2C+Kim+D%3BTatusova%2C+Tatiana%3BMaglott%2C+Donna+R&rft.aulast=Pruitt&rft.aufirst=Kim&rft.date=2005-01-01&rft.volume=33&rft.issue=&rft.spage=D501&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - genomics; Genetic mapping; Nucleotide sequence; Viruses; Eukaryotes; Prokaryotes; proteomics ER - TY - JOUR T1 - Entrez Gene: gene-centered information at NCBI AN - 17836338; 6174720 AB - Entrez Gene (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene) is NCBI's database for gene-specific information. It does not include all known or predicted genes; instead Entrez Gene focuses on the genomes that have been completely sequenced, that have an active research community to contribute gene- specific information, or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases, and from many other databases available from NCBI. Records are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes, and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is updated as new information becomes available. Entrez Gene is a step forward from NCBI's LocusLink, with both a major increase in taxonomic scope and improved access through the many tools associated with NCBI Entrez. JF - Nucleic Acids Research AU - Maglott, Donna AU - Ostell, Jim AU - Pruitt, Kim D AU - Tatusova, Tatiana AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Room 5AS.13B, 45 Center Drive, Bethesda, MD Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - D54 EP - D58 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 33 SN - 0305-1048, 0305-1048 KW - Entrez Gene KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Genetics Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Nomenclature KW - Loci KW - Gene expression KW - Genetic markers KW - Taxonomy KW - genomics KW - proteomics KW - Genetic mapping KW - N 14010:Physical & Computer Methods & Assays KW - W 30965:Miscellaneous, Reviews KW - G 07300:Theoretical genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17836338?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=Entrez+Gene%3A+gene-centered+information+at+NCBI&rft.au=Maglott%2C+Donna%3BOstell%2C+Jim%3BPruitt%2C+Kim+D%3BTatusova%2C+Tatiana&rft.aulast=Maglott&rft.aufirst=Donna&rft.date=2005-01-01&rft.volume=33&rft.issue=&rft.spage=D54&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Taxonomy; Gene expression; Genetic markers; Genetic mapping; proteomics; Nomenclature; Loci; genomics ER - TY - JOUR T1 - Breast Cancer Risk Among Women Who Start Smoking as Teenagers AN - 17833477; 6167242 AB - Objective: To examine the effect of smoking on breast cancer risk in a large population-based cohort of women, many of whom started smoking as teenagers. Methods: We followed 102,098 women, ages 30 to 50 years, completing a mailed questionnaire at recruitment to the Norwegian-Swedish Cohort Study in 1991/1992, through December 2000. We used Cox proportional hazard regression models to estimate relative risk (RR) of breast cancer associated with different measures of smoking initiation, duration, and intensity adjusting for confounding variables. We conducted analyses on the entire study population, among women who had smoked for at least 20 years, among nondrinkers, and separately for each country. Results: Altogether, 1,240 women were diagnosed with incident, invasive breast cancer. Compared with never smokers, women who smoked for at least 20 years and who smoked 10 cigarettes or more daily had a RR of 1.34 (95% CI, 1.06- 1.70). Likewise, those who initiated smoking prior to their first birth (1.27, 1.00-1.62), before menarche (1.39, 1.03-1.87), or before age 15 (1.48, 1.03- 2.13) had an increased risk. In contrast, women who had smoked for at least 20 years, but started after their first birth, did not experience an increased breast cancer risk. The increased RR associated with smoking was observed among nondrinkers of alcohol, women with and without a family history of breast cancer, premenopausal and postmenopausal women, and in both countries. Conclusion: Our results support the notion that women who start smoking as teenagers and continue to smoke for at least 20 years may increase their breast cancer risk. JF - Cancer Epidemiology, Biomarkers & Prevention AU - Gram, Inger T AU - Braaten, Tonje AU - Terry, Paul D AU - Sasco, Annie J AU - Adami, Hans-Olov AU - Lund, Eiliv AU - Weiderpass, Elisabete AD - Institute of Community Medicine, University of Tromsoe, NIEHS, Epidemiology Branch, Research Triangle Park, North Carolina Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 61 EP - 66 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 14 IS - 1 SN - 1055-9965, 1055-9965 KW - Toxicology Abstracts KW - Risk assessment KW - Birth KW - Smoking KW - Invasiveness KW - Post-menopause KW - Recruitment KW - Menarche KW - alcohols KW - Population studies KW - Breast cancer KW - biomarkers KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17833477?accountid=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+Epidemiology%2C+Biomarkers+%26+Prevention&rft.atitle=Breast+Cancer+Risk+Among+Women+Who+Start+Smoking+as+Teenagers&rft.au=Gram%2C+Inger+T%3BBraaten%2C+Tonje%3BTerry%2C+Paul+D%3BSasco%2C+Annie+J%3BAdami%2C+Hans-Olov%3BLund%2C+Eiliv%3BWeiderpass%2C+Elisabete&rft.aulast=Gram&rft.aufirst=Inger&rft.date=2005-01-01&rft.volume=14&rft.issue=1&rft.spage=61&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.issn=10559965&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 - Breast cancer; Smoking; Birth; biomarkers; alcohols; Recruitment; Invasiveness; Post-menopause; Menarche; Risk assessment; Population studies ER - TY - JOUR T1 - Cadmium-induced malignant transformation in rat liver cells: Role of aberrant oncogene expression and minimal role of oxidative stress AN - 17828126; 6153034 AB - Our study examined the role of oxidative stress and aberrant gene expression in malignant transformation induced by chronic, low-level cadmium exposure in non-tumorigenic rat liver epithelial cell line, TRL 1215. Cells were cultured in 1.0 mu M cadmium (as CdCl sub(2)) for up to 28 weeks and compared to passage- matched control cells. The level of cadmium used for transformation produced no evidence of increased superoxide (O sub(2) super(-.)) or hydrogen peroxide (H sub(2)O sub(2)) levels in the early stages of exposure (<=24 hr). The chronic cadmium exposed liver epithelial cells (CCE-LE) were hyperproliferative with a growth rate about 3-fold higher than control cells. CCE-LE cells produced highly aggressive tumors upon inoculation into mice confirming malignant transformation. Analysis of cellular reactive oxygen species (ROS) showed that CCE-LE cells possessed markedly lower basal levels of intracellular O sub(2) super(- .)and H sub(2)O sub(2) and were very tolerant to high-dose (50 mu M) cadmium-induced ROS. Time course studies showed the production of ROS by high-dose cadmium was abolished well in advance of malignant transformation. In contrast, marked overexpression of the oncogenes c-myc and c-jun occurred in transformed CCE-LE cells as evidenced by up to 10-fold increases in both transcript and protein. A significant increase in DNA-binding activity of the transcription factors AP-1 and NF- Kappa B occurred in CCE-LE cells. Increases in oncogene expression and transcription factor activity occurred concurrently with malignant transformation. Thus, cadmium-induced ROS occurs as an early, high-dose event but is abolished well in advance of malignant transformation. Low-level chronic cadmium triggers oncogene overexpression possibly by altering critical transcription factor activity. Such changes in cellular gene expression likely culminate in the loss of growth control and cadmium-induced neoplastic transformation in CCE-LE cells, whereas generation of ROS by cadmium seemed to play a minimal role in this transformation. JF - International Journal of Cancer AU - Qu, Wei AU - Diwan, Bhalchandra A AU - Reece, Jeffrey M AU - Bortner, Carl D AU - Pi, Jingbo AU - Liu, Jie AU - Waalkes, Michael P AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA, waalkes@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 346 EP - 355 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 114 IS - 3 SN - 0020-7136, 0020-7136 KW - Toxicology Abstracts KW - Growth rate KW - Transformation KW - Epithelial cells KW - Hepatocytes KW - Activator protein 1 KW - Transcription KW - NF-^KB protein KW - c-Jun protein KW - Gene expression KW - Oncogenes KW - Reactive oxygen species KW - Oxidative stress KW - Hydrogen peroxide KW - Superoxide KW - Transcription factors KW - Inoculation KW - Cadmium KW - c-Myc protein KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17828126?accountid=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+Cancer&rft.atitle=Cadmium-induced+malignant+transformation+in+rat+liver+cells%3A+Role+of+aberrant+oncogene+expression+and+minimal+role+of+oxidative+stress&rft.au=Qu%2C+Wei%3BDiwan%2C+Bhalchandra+A%3BReece%2C+Jeffrey+M%3BBortner%2C+Carl+D%3BPi%2C+Jingbo%3BLiu%2C+Jie%3BWaalkes%2C+Michael+P&rft.aulast=Qu&rft.aufirst=Wei&rft.date=2005-01-01&rft.volume=114&rft.issue=3&rft.spage=346&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.20736 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Transformation; Cadmium; Transcription factors; Oncogenes; Hepatocytes; Hydrogen peroxide; Reactive oxygen species; Epithelial cells; Gene expression; Oxidative stress; Inoculation; c-Jun protein; NF-^KB protein; Growth rate; c-Myc protein; Activator protein 1; Transcription; Superoxide DO - http://dx.doi.org/10.1002/ijc.20736 ER - TY - JOUR T1 - Parental occupational exposures and Ewing's sarcoma AN - 17825924; 6153053 AB - A case-control study of Ewing's sarcoma (ES) was conducted to search for occupational exposures associated with ES. The study consisted of 196 cases and 196 random-digit controls matched on geographical region, gender, ethnic origin and birth date. A questionnaire was administered to mothers of participants to obtain information on medical conditions, medications, and parental occupations during and after the index pregnancy. An occupational exposure expert coded jobs and industries for possible and probable exposure to selected occupational hazards. Risk of ES was increased with probable parental exposure to wood dusts during their usual occupation post pregnancy (odds ration [OR] = 3.2; 95% confidence interval [CI] = 1.1-9.2). Other exposures, including a priori suspected risk factors such as exposure to pesticides and farm animals, were not significantly associated with ES. A history of household pesticide extermination was associated with ES among boys aged 15 or younger (OR = 3.0; 95% CI = 1.1- 8.1), but not among girls or older boys. Our results suggest that earlier reports of associations of ES with parental farm employment may have been describing risks associated with organic dusts encountered when working on a farm, rather than agricultural exposures or other farming related exposures. JF - International Journal of Cancer AU - Moore, Lee E AU - Gold, Laura AU - Stewart, Patricia A AU - Gridley, Gloria AU - Prince, Jacqueline R AU - Zahm, Shelia Hoar AD - Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, MD, USA, moorele@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 472 EP - 478 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 114 IS - 3 SN - 0020-7136, 0020-7136 KW - Ewing's sarcoma KW - Risk Abstracts; Health & Safety Science Abstracts KW - Organic matter KW - Dust KW - Pesticides KW - Occupational exposure 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/17825924?accountid=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=Parental+occupational+exposures+and+Ewing%27s+sarcoma&rft.au=Moore%2C+Lee+E%3BGold%2C+Laura%3BStewart%2C+Patricia+A%3BGridley%2C+Gloria%3BPrince%2C+Jacqueline+R%3BZahm%2C+Shelia+Hoar&rft.aulast=Moore&rft.aufirst=Lee&rft.date=2005-01-01&rft.volume=114&rft.issue=3&rft.spage=472&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.20734 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Occupational exposure; Pesticides; Dust; Organic matter DO - http://dx.doi.org/10.1002/ijc.20734 ER - TY - JOUR T1 - Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China AN - 17825035; 6084909 AB - Esophageal cancer incidence and mortality rates in Linxian, China are among the highest in the world. We examined risk factors for esophageal squamous cell carcinoma (ESCC), gastric cardia cancer (GCC), and gastric noncardia cancer (GNCC) in a population-based, prospective study of 29,584 adults who participated in the Linxian General Population Trial. All study participants completed a baseline questionnaire that included questions on demographic characteristics, personal and family history of disease, and lifestyle factors. After 15 years of follow-up, a total of 3,410 incident upper gastrointestinal cancers were identified, including 1,958 ESCC, 1,089 GCC and 363 GNCC. Cox proportional hazard models were used to estimate risks. Increased age and a positive family history of esophageal cancer (including ESCC or GCC) were significantly associated with risk at all 3 cancer sites. Additional risk factors for ESCC included being born in Linxian, increased height, cigarette smoking and pipe smoking; for GCC, male gender, consumption of moldy breads and pipe smoking; and for GNCC, male gender and cigarette smoking. Protective factors for ESCC included formal education, water piped into the home, increased consumption of meat, eggs and fresh fruits and increased BMI; for GCC, formal education, water piped into the home, increased consumption of eggs and fresh fruits and alcohol consumption; and for GNCC, increased weight and BMI. General socioeconomic status (SES) is a common denominator in many of these factors and improving SES is a promising approach for reducing the tremendous burden of upper gastrointestinal cancers in Linxian. JF - International Journal of Cancer AU - Tran, Gina D AU - Sun, Xiu-Di AU - Abnet, Christian C AU - Fan, Jin-Hu AU - Dawsey, Sanford M AU - Dong, Zhi-Wei AU - Mark, Steven D AU - Qiao, You-Lin AU - Taylor, Philip R AD - Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA, ptaylor@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 456 EP - 463 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 113 IS - 3 SN - 0020-7136, 0020-7136 KW - esophagus KW - Risk Abstracts KW - Diets KW - Socioeconomics KW - Cancer KW - Demographics KW - Genetics KW - Gastrointestinal tract KW - China, People's Rep. KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17825035?accountid=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=Prospective+study+of+risk+factors+for+esophageal+and+gastric+cancers+in+the+Linxian+general+population+trial+cohort+in+China&rft.au=Tran%2C+Gina+D%3BSun%2C+Xiu-Di%3BAbnet%2C+Christian+C%3BFan%2C+Jin-Hu%3BDawsey%2C+Sanford+M%3BDong%2C+Zhi-Wei%3BMark%2C+Steven+D%3BQiao%2C+You-Lin%3BTaylor%2C+Philip+R&rft.aulast=Tran&rft.aufirst=Gina&rft.date=2005-01-01&rft.volume=113&rft.issue=3&rft.spage=456&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.20616 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - China, People's Rep.; Genetics; Demographics; Socioeconomics; Diets; Gastrointestinal tract; Cancer DO - http://dx.doi.org/10.1002/ijc.20616 ER - TY - JOUR T1 - GenBank AN - 17803796; 6174221 AB - GenBank super([reg.]) is a comprehensive database that contains publicly available DNA sequences for more than 165 000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web- based BankIt or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in the UK and the DNA Data Bank of Japan helps to ensure worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at http://www.ncbi.nlm.nih.gov. JF - Nucleic Acids Research AU - Benson, Dennis A AU - Karsch-Mizrachi, Ilene AU - Lipman, David J AU - Ostell, James AU - Wheeler, David L AD - Department of Health and Human Services, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A, 8600 Rockville Pike, Bethesda, MD Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - D34 EP - D38 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 33 SN - 0305-1048, 0305-1048 KW - GenBank KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Genomes KW - Peptide mapping KW - Nucleotide sequence KW - Protein structure KW - Data banks KW - Computer programs KW - Blast KW - Databases KW - Taxonomy KW - Amino acid sequence KW - Gene mapping KW - G 07120:Recombinant DNA/Genetic engineering KW - N 14020:DNA/RNA genomics sequence KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17803796?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=GenBank&rft.au=Benson%2C+Dennis+A%3BKarsch-Mizrachi%2C+Ilene%3BLipman%2C+David+J%3BOstell%2C+James%3BWheeler%2C+David+L&rft.aulast=Benson&rft.aufirst=Dennis&rft.date=2005-01-01&rft.volume=33&rft.issue=&rft.spage=D34&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Databases; Nucleotide sequence; Blast; Data banks; Peptide mapping; Computer programs; Genomes; Gene mapping; Taxonomy; Protein structure; Amino acid sequence ER - TY - JOUR T1 - PCR Testing of Pooled Longitudinally Collected Cervical Specimens of Women to Increase the Efficiency of Studying Human Papillomavirus Infection AN - 17803076; 6167098 AB - In large active cohort studies of women investigating human papillomavirus (HPV) and cervical neoplasia, many women will be HPV-negative at all time points and testing of all their cervical specimens is an inefficient use of laboratory resources. The aim of this pilot study was to evaluate whether pooling cervical specimens from the same woman might provide a useful pretest of specimens from women unlikely to have high-grade cervical neoplasia or significant HPV exposure. We selected women (n = 187) participating in the Guanacaste Project for whom we already had HPV testing data on all their specimens from multiple visits (median = 8 visits), who were HPV DNA-negative at enrollment and at their 5-to 7-year exit from the cohort, and had no evidence of high-grade cervical neoplasia. Equal aliquots of cervical specimens from these women were pooled to create a proportional pooled specimen. Aliquots of pooled specimens were tested in a masked fashion by MY09/11 L1 consensus primer PCR. Second aliquots of some pooled specimens (n = 83) were included to assess the reliability of pooled testing. Results were compared with the predicted (expected) results based on the obtained test results of the individual specimens collected at interim visits. There was good overall agreement between observed and expected HPV DNA positivity, with a Kappa of 0.63 [95% confidence interval (95% CI), 0.51-0.75] and a percent agreement of 83.4% (95% CI, 77.3-88.5%) although the HPV DNA positivity in the pooled specimen was less than expected (P = 0.001). The agreement between observed and expected HPV DNA positivity was related to the number of aliquots pooled, suggesting that positivity was related to viral genome concentrations. The Kappa and percent agreement for intra-batch reliability of testing pooled specimens were 0.68 (95% CI, 0.53-0.84) and 84.3% (95% CI, 74.7-91.4%), respectively. We conclude that pooling specimens and testing by PCR may be useful for discriminating HPV DNA-positive from completely negative specimen sets in women who are likely to have been HPV DNA-negative.> JF - Cancer Epidemiology, Biomarkers & Prevention AU - Castle, Philip E AU - Schiffman, Mark AU - Herrero, Rolando AU - Hildesheim, Allan AU - Rodriguez, Ana-Cecilia AU - Bratti, MConcepcion AU - Wacholder, Sholom AU - Kendal, Hortense AU - Breheny, Anne M AU - Prior, Andrew AU - Pfeiffer, Ruth AU - Burk, Robert D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 256 EP - 260 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 14 IS - 1 SN - 1055-9965, 1055-9965 KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Genomes KW - biomarkers KW - Neoplasia KW - Polymerase chain reaction KW - Primers KW - Cervix KW - Human papillomavirus KW - A 01114:Viruses KW - V 22121:Diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17803076?accountid=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=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.atitle=PCR+Testing+of+Pooled+Longitudinally+Collected+Cervical+Specimens+of+Women+to+Increase+the+Efficiency+of+Studying+Human+Papillomavirus+Infection&rft.au=Castle%2C+Philip+E%3BSchiffman%2C+Mark%3BHerrero%2C+Rolando%3BHildesheim%2C+Allan%3BRodriguez%2C+Ana-Cecilia%3BBratti%2C+MConcepcion%3BWacholder%2C+Sholom%3BKendal%2C+Hortense%3BBreheny%2C+Anne+M%3BPrior%2C+Andrew%3BPfeiffer%2C+Ruth%3BBurk%2C+Robert+D&rft.aulast=Castle&rft.aufirst=Philip&rft.date=2005-01-01&rft.volume=14&rft.issue=1&rft.spage=256&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.issn=10559965&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 papillomavirus; Cervix; Neoplasia; Polymerase chain reaction; Genomes; Primers; biomarkers ER - TY - JOUR T1 - National Toxicology Program Center for the Evaluation of Risks to Human Reproduction: Guidelines for CERHR Expert Panel members AN - 17799793; 6152606 AB - No Abstract JF - Birth Defects Research Part B: Developmental and Reproductive Toxicology AU - Shelby, Michael D AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, Shelby@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 9 EP - 16 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 74 IS - 1 SN - 1542-9733, 1542-9733 KW - Toxicology Abstracts KW - Guidelines KW - Congenital defects KW - Reproduction KW - X 24230:Legislation & recommended standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17799793?accountid=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=Birth+Defects+Research+Part+B%3A+Developmental+and+Reproductive+Toxicology&rft.atitle=National+Toxicology+Program+Center+for+the+Evaluation+of+Risks+to+Human+Reproduction%3A+Guidelines+for+CERHR+Expert+Panel+members&rft.au=Shelby%2C+Michael+D&rft.aulast=Shelby&rft.aufirst=Michael&rft.date=2005-01-01&rft.volume=74&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Birth+Defects+Research+Part+B%3A+Developmental+and+Reproductive+Toxicology&rft.issn=15429733&rft_id=info:doi/10.1002%2Fbdrb.20029 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Guidelines; Congenital defects; Reproduction DO - http://dx.doi.org/10.1002/bdrb.20029 ER - TY - JOUR T1 - The Diphtheria and Pertussis Components of Diphtheria-Tetanus Toxoids-Pertussis Vaccine Should Be Genetically Inactivated Mutant Toxins AN - 17799392; 6129911 AB - Replacement of cellular with acellular pertussis (aP) vaccines has considerably reduced the systemic reactions observed with diphtheria-tetanus toxoids-pertussis vaccine but has not eliminated the extensive swelling (sometimes involving an entire limb) observed after the fifth injection of diphtheria-tetanus toxoids-aP (DTaP) vaccine. This local reaction, which is likely an Arthus hypersensitivity reaction caused by high levels of antibodies reacting with DTaP vaccine, could discourage its use in adults, who serve as the major reservoir of pertussis for infants. That a critical level of antibodies to pertussis toxin is both essential and sufficient to prevent infection with Bordetella pertussis is derived from data from animal and clinical studies, including data showing the similarities between the immunity induced by diphtheria and pertussis toxoids. The genetically inactivated diphtheria and pertussis mutant toxins are more immunogenic and, therefore, induce comparable levels of antitoxin at lower protein levels than do the formalin-treated native toxins. Replacement of the diphtheria and aP components with these improved antigens will reduce the amount of protein in DTaP vaccine and, most likely, the incidence and severity of local reactions in teenagers and adults. JF - Journal of Infectious Diseases AU - Robbins, J B AU - Schneerson, R AU - Trollfors, B AU - Sato, H AU - Sato, Y AU - Rappuoli, R AU - Keith, J M AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - 81 EP - 88 VL - 191 IS - 1 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts B: Bacteriology KW - Antitoxins KW - Pertussis KW - Antibodies KW - Bordetella pertussis KW - Limbs KW - Toxoids KW - Diphtheria KW - Vaccines KW - Swelling KW - Infants KW - pertussis toxin KW - J 02834:Vaccination and immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17799392?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+Diphtheria+and+Pertussis+Components+of+Diphtheria-Tetanus+Toxoids-Pertussis+Vaccine+Should+Be+Genetically+Inactivated+Mutant+Toxins&rft.au=Robbins%2C+J+B%3BSchneerson%2C+R%3BTrollfors%2C+B%3BSato%2C+H%3BSato%2C+Y%3BRappuoli%2C+R%3BKeith%2C+J+M&rft.aulast=Robbins&rft.aufirst=J&rft.date=2005-01-01&rft.volume=191&rft.issue=1&rft.spage=81&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 - Bordetella pertussis; Pertussis; Vaccines; Diphtheria; Antibodies; Swelling; Toxoids; pertussis toxin; Antitoxins; Limbs; Infants ER - TY - JOUR T1 - Genome-genome interactions: bacterial communities in initial dental plaque AN - 17796365; 6136136 AB - The usual context for genome-genome interactions is DNA-DNA interactions, but the manifestation of the genome is the cell. Here we focus on cell-cell interactions and relate them to the process of building multi-species biofilm communities. We propose that dental plaque communities originate as a result of intimate interactions between cells (genomes) of different species and not through clonal growth of genetically identical cells. Although DNA exchange might occur between cells within these communities, we limit our opinions to discussions of the spatiotemporal and metabolic relationships that exist here. We believe the multi-species interactions occurring during the early stages of biofilm formation determine the species composition and nature of the mature biofilm. The human oral cavity provides easy access to natural biofilms on a retrievable enamel chip, which is an excellent model for the study of genome- genome interactions. JF - Trends in Microbiology AU - Kolenbrander, P E AU - Egland, P G AU - Diaz, P I AU - Palmer, R J AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20902, USA, pkolenbrander@dir.nidcr.nih.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 11 EP - 15 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 13 IS - 1 SN - 0966-842X, 0966-842X KW - Microbiology Abstracts B: Bacteriology KW - Genomes KW - Enamel KW - Reviews KW - DNA KW - Species composition KW - Biofilms KW - Dental plaque KW - Oral cavity KW - J 02844:Dental and oral KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17796365?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+Microbiology&rft.atitle=Genome-genome+interactions%3A+bacterial+communities+in+initial+dental+plaque&rft.au=Kolenbrander%2C+P+E%3BEgland%2C+P+G%3BDiaz%2C+P+I%3BPalmer%2C+R+J&rft.aulast=Kolenbrander&rft.aufirst=P&rft.date=2005-01-01&rft.volume=13&rft.issue=1&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Trends+in+Microbiology&rft.issn=0966842X&rft_id=info:doi/10.1016%2Fj.tim.2004.11.005 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Biofilms; Genomes; Dental plaque; Enamel; Reviews; Species composition; DNA; Oral cavity DO - http://dx.doi.org/10.1016/j.tim.2004.11.005 ER - TY - JOUR T1 - Gingival Carcinogenicity in Female Harlan Sprague-Dawley Rats following Two-Year Oral Treatment with 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Dioxin-Like Compounds AN - 17776837; 6177464 AB - We evaluated gingival toxicities induced by chronic exposure of female Harlan Sprague-Dawley rats to dioxin and dioxin-like compounds (DLCs) and compared them to similarly induced oral lesions reported in the literature. This investigation represents part of an ongoing initiative of the National Toxicology Program to determine the relative potency of chronic toxicity and carcinogenicity of polychlorinated dioxins, furans, and biphenyls. For two years, animals were administered by gavage 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); 3,3',4,4',5-pentachlorobiphenyl (PCB126); 2,3,4,7,8- pentachlorodibenzofuran (PeCDF); 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153); a tertiary mixture of TCDD, PCB126, and PeCDF; a binary mixture of PCB126 and 153; or a binary mixture of PCB126 and 2,3',4,4',5-pentachlorobiphenyl (PCB118); control animals received corn oil-acetone vehicle (99:1) alone. A full complement of tissues, including the palate with teeth, was examined microscopically. In the groups treated with TCDD and the mixtures of TCDD, PCB126, and PeCDF; PCB126 and 153; and PCB126 and 118, the incidences of gingival squamous hyperplasia increased significantly. Moreover, in the groups treated with TCDD, PCB126, and the mixture of PCB126 and 153, squamous cell carcinoma (SCC) in the oral cavity increased significantly. This investigation constitutes the first report documenting that chronic administration of dioxin- like PCBs can induce gingival SCC in rats. These results indicate that dioxin and DLCs target the gingiva of the oral cavity, in particular the junctional epithelium of molars. JF - Toxicological Sciences AU - Yoshizawa, Katsuhiko AU - Walker, Nigel J AU - Jokinen, Micheal P AU - Brix, Amy E AU - Sells, Donald M AU - Marsh, Tiwanda AU - Wyde, Michael E AU - Orzech, Denise AU - Haseman, Joseph K AU - Nyska, Abraham AD - Laboratory of Experimental Pathology, Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 64 EP - 77 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 83 IS - 1 SN - 1096-6080, 1096-6080 KW - Toxicology Abstracts KW - Molars KW - Gingiva KW - 3,3',4,4',5-Pentachlorobiphenyl KW - TCDD KW - squamous cell carcinoma KW - Palate KW - Oral cavity KW - Hyperplasia KW - Chronic exposure KW - Carcinogenicity KW - Chronic toxicity KW - Epithelium KW - PCB KW - Dioxin KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17776837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Gingival+Carcinogenicity+in+Female+Harlan+Sprague-Dawley+Rats+following+Two-Year+Oral+Treatment+with+2%2C3%2C7%2C8-Tetrachlorodibenzo-p-dioxin+and+Dioxin-Like+Compounds&rft.au=Yoshizawa%2C+Katsuhiko%3BWalker%2C+Nigel+J%3BJokinen%2C+Micheal+P%3BBrix%2C+Amy+E%3BSells%2C+Donald+M%3BMarsh%2C+Tiwanda%3BWyde%2C+Michael+E%3BOrzech%2C+Denise%3BHaseman%2C+Joseph+K%3BNyska%2C+Abraham&rft.aulast=Yoshizawa&rft.aufirst=Katsuhiko&rft.date=2005-01-01&rft.volume=83&rft.issue=1&rft.spage=64&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gingiva; TCDD; Dioxin; Molars; Carcinogenicity; Oral cavity; squamous cell carcinoma; Chronic exposure; Hyperplasia; 3,3',4,4',5-Pentachlorobiphenyl; Palate; PCB; Epithelium; Chronic toxicity ER - TY - JOUR T1 - Chlamydia pneumoniae Enhances Cytokine-Stimulated Human Monocyte Matrix Metalloproteinases through a Prostaglandin E sub(2)-Dependent Mechanism AN - 17773284; 6117749 AB - Exposure of human monocytes to Chlamydia pneumoniae resulted in a significant enhancement of matrix metalloproteinase (MMP) 1 and 9 production following stimulation with tumor necrosis factor alpha and granulocyte monocyte- colony stimulating factor. The effect of C. pneumoniae on monocyte MMPs was mediated through the induction of prostaglandin E sub(2). These findings may have implications for atherosclerotic plaque rupture. JF - Infection and Immunity AU - Kim, Min P AU - Gaydos, Charlotte A AU - Wood, Billie Jo AU - Hardick, Justin P AU - Zhang, Yahong AU - Wahl, Larry M AD - National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 632 EP - 634 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 73 IS - 1 SN - 0019-9567, 0019-9567 KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Matrix metalloproteinase KW - Arteriosclerosis KW - Prostaglandin E2 KW - Tumor necrosis factor-a KW - Leukocytes (granulocytic) KW - Chlamydia pneumoniae KW - Tumor necrosis factor-^a KW - Monocytes KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17773284?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chlamydia+pneumoniae+Enhances+Cytokine-Stimulated+Human+Monocyte+Matrix+Metalloproteinases+through+a+Prostaglandin+E+sub%282%29-Dependent+Mechanism&rft.au=Kim%2C+Min+P%3BGaydos%2C+Charlotte+A%3BWood%2C+Billie+Jo%3BHardick%2C+Justin+P%3BZhang%2C+Yahong%3BWahl%2C+Larry+M&rft.aulast=Kim&rft.aufirst=Min&rft.date=2005-01-01&rft.volume=73&rft.issue=1&rft.spage=632&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia pneumoniae; Monocytes; Matrix metalloproteinase; Tumor necrosis factor-a; Leukocytes (granulocytic); Prostaglandin E2; Arteriosclerosis; Tumor necrosis factor-^a ER - TY - JOUR T1 - Both Innate Immunity and Type 1 Humoral Immunity to Streptococcus pneumoniae Are Mediated by MyD88 but Differ in Their Relative Levels of Dependence on Toll-Like Receptor 2 AN - 17766848; 6117687 AB - Little is known regarding the role of Toll-like receptors (TLRs) in regulating protein-and polysaccharide-specific immunoglobulin (Ig) isotype production in response to an in vivo challenge with an extracellular bacterium. In this report we demonstrate that MyD88 super(-/-), but not TLR2 super(-/-), mice are markedly defective in their induction of multiple splenic proinflammatory cytokine-and chemokine-specific mRNAs after intraperitoneal (i.p.) challenge with heat-killed Streptococcus pneumoniae capsular type 14 (S. pneumoniae type 14). This is correlated with analogous responses in splenic cytokine protein release in vitro following addition of S. pneumoniae type 14. Consistent with these data, naive MyD88 super(-/-), but not TLR2 super(-/-), mice are more sensitive to killing following i.p. challenge with live S. pneumoniae type 14, relative to responses in wild-type mice. However, prior immunization of MyD88 super(-/-) mice with heat-killed S. pneumoniae type 14 protects against an otherwise-lethal challenge with live S. pneumoniae type 14. Surprisingly, both MyD88 super(-/-) and TLR2 super(-/-) mice exhibit striking and equivalent defects in elicitation of type 1 IgG isotypes (IgG3, IgG2b, and IgG2a), but not the type 2 IgG isotype, IgG1, specific for several protein and polysaccharide antigens, in response to i.p. challenge with heat-killed S. pneumoniae type 14. Of note, the type 1 IgG isotype titers specific for pneumococcal surface protein A are reduced in MyD88 super(-/-) mice but not TLR2 super(-/-) mice. These data suggest that distinct TLRs may differentially regulate innate versus adaptive humoral immunity to intact S. pneumoniae and are the first to implicate a role for TLR2 in shaping an in vivo type 1 IgG humoral immune response to a gram-positive extracellular bacterium. JF - Infection and Immunity AU - Khan, Abdul Q AU - Chen, Quanyi AU - Wu, Zheng-Qi AU - Paton, James C AU - Snapper, Clifford M AD - Department of Pathology, Uniformed Services University of the Health Sciences. Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 298 EP - 307 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 73 IS - 1 SN - 0019-9567, 0019-9567 KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - MyD88 protein KW - TLR2 protein KW - Spleen KW - Inflammation KW - Immunity (humoral) KW - surface protein A KW - Streptococcus pneumoniae KW - Immunoglobulin G KW - Cytokines KW - Immune response (humoral) KW - Toll-like receptors KW - F 06807:Active immunization KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17766848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Both+Innate+Immunity+and+Type+1+Humoral+Immunity+to+Streptococcus+pneumoniae+Are+Mediated+by+MyD88+but+Differ+in+Their+Relative+Levels+of+Dependence+on+Toll-Like+Receptor+2&rft.au=Khan%2C+Abdul+Q%3BChen%2C+Quanyi%3BWu%2C+Zheng-Qi%3BPaton%2C+James+C%3BSnapper%2C+Clifford+M&rft.aulast=Khan&rft.aufirst=Abdul&rft.date=2005-01-01&rft.volume=73&rft.issue=1&rft.spage=298&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Streptococcus pneumoniae; Toll-like receptors; Immunoglobulin G; Spleen; Immunity (humoral); Inflammation; MyD88 protein; Cytokines; TLR2 protein; Immune response (humoral); surface protein A ER - TY - JOUR T1 - Absence of toxic effects in F344/N rats and B6C3F sub(1) mice following subchronic administration of chromium picolinate monohydrate AN - 17762505; 6132545 AB - Chromium picolinate monohydrate (CPM) is a synthetic compound heavily marketed to consumers in the United States for use as a dietary supplement for muscle building and weight loss. The National Toxicology Program (NTP) tested the toxicity of this compound based on the potential for widespread consumer exposure and lack of information about its toxicity. Groups of 10 male and 10 female F344/N rats and B6C3F sub(1) mice were exposed to 0, 80, 240, 2000, 10, 000, or 50, 000 ppm CPM in feed for 13 weeks. CPM administration produced no effect on body weight gain or survival of rats or mice. Organ weights and organ/body weight ratios in exposed animals were generally unaffected by CPM. No compound-related changes in hematology and clinical chemistry parameters were observed. There were no histopathological lesions attributed to CPM in rats or mice. JF - Food and Chemical Toxicology AU - Rhodes, M C AU - Hebert, C D AU - Herbert, R A AU - Morinello, E J AU - Roycroft, J H AU - Travlos, G S AU - Abdo, K M AD - National Institute of Environmental Health Sciences, Mail Drop EC-34, 79 TW Alexander Drive, Research Triangle Park, NC 27709, United States, rhodes2@niehs.nih.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 21 EP - 29 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 - 43 IS - 1 SN - 0278-6915, 0278-6915 KW - mice KW - rats KW - Toxicology Abstracts KW - Chromium KW - Feed KW - Mice KW - NTP KW - Picolinate KW - Rats KW - Subchronic KW - Supplement KW - Toxicity KW - CPM, chromium picolinate monohydrate KW - NTP, National Toxicology Program KW - 8-OHdG, 8-hydroxydeoxyguanosine KW - Body weight KW - Dietary supplements KW - Survival KW - Lesions KW - Consumers KW - Body weight gain KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17762505?accountid=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=Food+and+Chemical+Toxicology&rft.atitle=Absence+of+toxic+effects+in+F344%2FN+rats+and+B6C3F+sub%281%29+mice+following+subchronic+administration+of+chromium+picolinate+monohydrate&rft.au=Rhodes%2C+M+C%3BHebert%2C+C+D%3BHerbert%2C+R+A%3BMorinello%2C+E+J%3BRoycroft%2C+J+H%3BTravlos%2C+G+S%3BAbdo%2C+K+M&rft.aulast=Rhodes&rft.aufirst=M&rft.date=2005-01-01&rft.volume=43&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Food+and+Chemical+Toxicology&rft.issn=02786915&rft_id=info:doi/10.1016%2Fj.fct.2004.08.006 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Body weight; Chromium; Dietary supplements; Lesions; Survival; Consumers; Toxicity; Body weight gain DO - http://dx.doi.org/10.1016/j.fct.2004.08.006 ER - TY - JOUR T1 - An enriched look at tyrosine phosphorylation AN - 17723242; 6133546 AB - Immunoaffinity isolation enables the identification of phosphotyrosine peptides on a global level. JF - Nature Biotechnology AU - Conrads, Thomas P AU - Veenstra, Timothy D AD - Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., National Cancer Institute at Frederick, P.O. Box B, Frederick, MD 21702-1201, USA, conrads@ncifcrf.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 36 EP - 37 PB - Nature Publishing Group VL - 23 IS - 1 SN - 1087-0156, 1087-0156 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - Cell survival KW - phosphotyrosine KW - Tumor cell lines KW - Phosphorylation KW - Protein-tyrosine kinase KW - phosphoproteomes KW - Spectrometry KW - Antibodies KW - Reviews KW - proteomics KW - Cell proliferation KW - Signal transduction KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - W3 33240:Immunology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17723242?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=An+enriched+look+at+tyrosine+phosphorylation&rft.au=Conrads%2C+Thomas+P%3BVeenstra%2C+Timothy+D&rft.aulast=Conrads&rft.aufirst=Thomas&rft.date=2005-01-01&rft.volume=23&rft.issue=1&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2Fnbt0105-36 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Protein-tyrosine kinase; proteomics; Signal transduction; Tumor cell lines; Cell survival; Spectrometry; Cell proliferation; Antibodies; phosphoproteomes; Reviews; Phosphorylation; phosphotyrosine DO - http://dx.doi.org/10.1038/nbt0105-36 ER - TY - JOUR T1 - Depolymerization of beta-1,6-N-Acetyl-D-Glucosamine Disrupts the Integrity of Diverse Bacterial Biofilms AN - 17698291; 6117899 AB - Polymeric beta-1,6-N-acetyl-D-glucosamine (poly-beta-1,6-GlcNAc) has been implicated as an Escherichia coli and Staphylococcus epidermidis biofilm adhesin, the formation of which requires the pgaABCD and icaABCD loci, respectively. Enzymatic hydrolysis of poly-beta-1,6-GlcNAc, demonstrated for the first time by chromatography and mass spectrometry, disrupts biofilm formation by these species and by Yersinia pestis and Pseudomonas fluorescens, which possess pgaABCD homologues. JF - Journal of Bacteriology AU - Itoh, Yoshikane AU - Wang, Xin AU - Hinnebusch, BJoseph AU - Preston, James F AU - Romeo, Tony AD - Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia. Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana. Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida Y1 - 2005/01/01/ PY - 2005 DA - 2005 Jan 01 SP - 382 EP - 387 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 187 IS - 1 SN - 0021-9193, 0021-9193 KW - Microbiology Abstracts B: Bacteriology KW - Pseudomonas fluorescens KW - Adhesins KW - Depolymerization KW - Chromatography KW - Escherichia coli KW - Yersinia pestis KW - N-Acetyl-D-glucosamine KW - Biofilms KW - Staphylococcus epidermidis KW - Hydrolysis KW - Spectrometry KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17698291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Depolymerization+of+beta-1%2C6-N-Acetyl-D-Glucosamine+Disrupts+the+Integrity+of+Diverse+Bacterial+Biofilms&rft.au=Itoh%2C+Yoshikane%3BWang%2C+Xin%3BHinnebusch%2C+BJoseph%3BPreston%2C+James+F%3BRomeo%2C+Tony&rft.aulast=Itoh&rft.aufirst=Yoshikane&rft.date=2005-01-01&rft.volume=187&rft.issue=1&rft.spage=382&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Adhesins; Depolymerization; Chromatography; N-Acetyl-D-glucosamine; Biofilms; Hydrolysis; Spectrometry; Pseudomonas fluorescens; Escherichia coli; Yersinia pestis; Staphylococcus epidermidis ER - TY - JOUR T1 - Chemical-Induced Atrial Thrombosis in NTP Rodent Studies AN - 17662692; 6539062 AB - Cardiac thrombosis, one of the causes of sudden death throughout the world, plays a principal role in several cardiovascular diseases, such as myocardial infarction and stroke in humans. Data from studies of induction of chemical thrombosis in rodents help to identify substances in our environment that may contribute to cardiac thrombosis. Results for more than 500 chemicals tested in rodents in 2-year bioassays have been published as Technical Reports of the National Toxicology Program (NTP) http://ntp-server.niehs.nih.gov/index. We evaluated atrial thrombosis induced by these chemical exposures and compared it to similarly induced lesions reported in the literature. Spontaneous rates of cardiac thrombosis were determined for control Fischer 344 rats and B6C3F1 mice: 0% in rats and mice in 90-day studies and, in 2-year studies, 0.7% in both genders of mice, 4% in male rats, and 1% in female rats. Incidences of atrial thrombosis were increased in high-dosed groups involving 13 compounds (incidence rate: 20-100%): 2-butoxyethanol, C.I. Direct Blue 15, bis(2-chloroethoxy)methane, diazoaminobenzene, diethanolamine, 3,3'-dimethoxybenzidine dihydrochloride, hexachloroethane, isobutene, methyleugenol, oxazepam, C.I. Pigment Red 23, C.I. Acid Red 114, and 4,4'-thiobis(6-t-butyl-m-cresol). The main localization of spontaneously occurring and chemically induced thromboses occurred in the left atrium. The literature survey suggested that chemical-induced atrial thrombosis might be closely related to myocardial injury, endothelial injury, circulatory stasis, hypercoagulability, and impaired atrial mechanical activity, such as atrial fibrillation, which could cause stasis of blood within the left atrial appendage, contributing to left atrial thrombosis. JF - Toxicologic Pathology AU - Yoshizawa, K AU - Kissling, GE AU - Johnson, JA AU - Clayton, N P AU - Flagler, N D AU - Nyska, A AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, 27709, USA Y1 - 2005 PY - 2005 DA - 2005 SP - 517 EP - 532 VL - 33 IS - 5 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17662692?accountid=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=Chemical-Induced+Atrial+Thrombosis+in+NTP+Rodent+Studies&rft.au=Yoshizawa%2C+K%3BKissling%2C+GE%3BJohnson%2C+JA%3BClayton%2C+N+P%3BFlagler%2C+N+D%3BNyska%2C+A&rft.aulast=Yoshizawa&rft.aufirst=K&rft.date=2005-01-01&rft.volume=33&rft.issue=5&rft.spage=517&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1080%2F01926230591034429 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-12-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1080/01926230591034429 ER - TY - JOUR T1 - Cancer incidence in the Agricultural Health Study AN - 17661821; 6515221 AB - This large, prospective cohort study of private applicators, commercial applicators, and spouses of farmer applicators was undertaken to ascertain the etiology of cancers elevated in agriculture. The participants were matched to cancer registry files in Iowa and North Carolina. Incident cases were identified from enrollment through 31 December 2002. Standardized incidence ratios (SIR) were used to compare the cancer incidence of the participants with that of the total population in the two states. The overall cancer incidence among farmers [SIR 0.88, 95% confidence interval (95% CI) 0.84-0.91] and their spouses (SIR 0.84, 95% CI 0.80-0.90) were significantly lower than expected, particularly for respiratory and urinary cancers. Commercial pesticide applicators had an overall cancer incidence comparable with the expected (SIR 1.01, 95% CI 0.84-1.20). Smoking prevalence was significantly lower than the national average. Prostate cancer was elevated among private applicators (SIR 1.24, 95% CI 1.18-1.33) and commercial applicators (SIR 1.37, 0.98-1.86). Excess ovarian cancer was observed for female applicators (SIR 2.97, 95% CI 1.28-5.85), but not for female spouses (SIR 0.55, 95% CI 0.38-0.78). Female spouses had a significant excess of melanoma (SIR 1.64, 95% CI 1.24-2.09), which was not observed among pesticide applicators. Low overall cancer incidence rates seem to be a result of low overall smoking prevalence and other lifestyle factors, while excess cancer of the prostate and ovaries among applicators may be occupationally related. The excess risk of melanoma observed among spouses was unexpected. JF - Scandinavian Journal of Work, Environment & Health AU - Alavanja, MCR AU - Sandler, D P AU - Lynch, C F AU - Knott, C AU - Lubin, J H AU - Tarone, R AU - Thomas, K AU - Dosemeci, M AU - Barker, J AU - Hoppin, JA AU - Blair, A AD - Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Room 8000, Rockville, MD 20892, USA, alavanjm@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 39 EP - 45 VL - 31 SN - 0355-3140, 0355-3140 KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - H 5000:Pesticides KW - X 24136:Environmental impact UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17661821?accountid=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=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.atitle=Cancer+incidence+in+the+Agricultural+Health+Study&rft.au=Alavanja%2C+MCR%3BSandler%2C+D+P%3BLynch%2C+C+F%3BKnott%2C+C%3BLubin%2C+J+H%3BTarone%2C+R%3BThomas%2C+K%3BDosemeci%2C+M%3BBarker%2C+J%3BHoppin%2C+JA%3BBlair%2C+A&rft.aulast=Alavanja&rft.aufirst=MCR&rft.date=2005-01-01&rft.volume=31&rft.issue=&rft.spage=39&rft.isbn=&rft.btitle=&rft.title=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-12-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Integrating exposure measurements into epidemiologic studies in agriculture AN - 17658227; 6515231 AB - Agricultural epidemiology studies frequently rely on questionnaires to assess pesticide exposure. Farmers can provide accurate information regarding their pesticide use history. However, pesticide exposure is influenced not only by the pesticide, but also by factors related to pesticide application and behavior; estimates of exposure can be improved by incorporating data on these factors. Exposure measurement studies help to elucidate influential factors with regard to pesticide dose. These factors can be incorporated into exposure estimates to reduce measurement error and allow for better resolution of the exposure distribution. In the Agricultural Health Study, two exposure algorithms were developed to evaluate exposure intensity; this exposure intensity score was used to modify the lifetime days of pesticide application. This metric, along with additional refinement as a result of on-going field studies, will allow better assignment of exposure levels in the cohort. Future work to develop exposure metrics that incorporate both chemical and behavior characteristics for all farmworkers and farm residents will further improve epidemiologic studies in agriculture. JF - Scandinavian Journal of Work, Environment & Health AU - Hoppin, JA AD - NIEHS, Epidemiology Branch, MD A3-05, PO Box 12233, Research Triangle Park, NC 27709-2233, USA, hoppin1@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 115 EP - 117 VL - 31 SN - 0355-3140, 0355-3140 KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - H 5000:Pesticides KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17658227?accountid=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=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.atitle=Integrating+exposure+measurements+into+epidemiologic+studies+in+agriculture&rft.au=Hoppin%2C+JA&rft.aulast=Hoppin&rft.aufirst=JA&rft.date=2005-01-01&rft.volume=31&rft.issue=&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-12-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - The plasmids of Borrelia burgdorferi: essential genetic elements of a pathogen AN - 17638590; 6387784 AB - The spirochete Borrelia burgdorferi, the causative agent of Lyme disease, has an unusual genome comprised of a linear chromosome and the largest plasmid complement of any characterized bacterium. Certain plasmid-encoded elements are required for virulence and viability, both in vitro and in vivo. The genetic tools to manipulate B. burgdorferi are sufficiently developed for precise molecular genetic investigations. B. burgdorferi now represents a prime system with which to address basic questions of plasmid biology and plasmid contributions to bacterial virulence and disease pathogenesis. JF - Plasmid AU - Stewart, P E AU - Byram, R AU - Grimm, D AU - Tilly, K AU - Rosa, P A AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840, USA, pestewart@niaid.nih.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 1 EP - 13 VL - 53 IS - 1 SN - 0147-619X, 0147-619X KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - J 02760:Plasmids KW - G 07320:Bacterial genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17638590?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Plasmid&rft.atitle=The+plasmids+of+Borrelia+burgdorferi%3A+essential+genetic+elements+of+a+pathogen&rft.au=Stewart%2C+P+E%3BByram%2C+R%3BGrimm%2C+D%3BTilly%2C+K%3BRosa%2C+P+A&rft.aulast=Stewart&rft.aufirst=P&rft.date=2005-01-01&rft.volume=53&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Plasmid&rft.issn=0147619X&rft_id=info:doi/10.1016%2Fj.plasmid.2004.10.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.plasmid.2004.10.006 ER - TY - JOUR T1 - In Vitro Antibody Evolution Targeting Germline Hot Spots to Increase Activity of an Anti-CD22 Immunotoxin AN - 17637261; 6437226 AB - Recombinant immunotoxin BL22, containing the Fv portion of an anti-CD22 antibody, produced complete remissions in most patients with drug-resistant hairy cell leukemia but had less activity in leukemias with low CD22 expression. Complementarity-determining region (CDR) mutagenesis is used to increase antibody affinity but can be difficult to perform successfully. We previously showed that antibodies with increased affinity and immunotoxins with increased activity could be obtained by directing mutations at specific DNA residues called hot spots. Because hot spots can arise either by somatic mutation or be present in the germline, we examined which type of hot spot is preferred for increasing antibody affinity. Initially, a second generation antibody phage-display library targeting a germline hot spot (Ser super(30)-Asn super(31)) within CDR1 of the antibody light chain was mutated. Substitution of serine 30 or asparagine 31 with arginine produced mutant immunotoxins with an affinity (0.8 nM) increased 7-fold over BL22 (5.8 nM) and 3-fold over the first generation mutant HA22 (2.3 nM). More importantly, a 10-fold increase in activity over BL22 and a 2-3-fold increase over HA22 were observed in various B lymphoma cell lines including WSU-CLL that contains only 5500 CD22 sites per cell. For comparison, two phage-display libraries targeting non-germline hot spots in heavy chain CDR1 and CDR3 were generated but did not produce Fv with increased affinity. Our results demonstrate that germline hot spots but not non-germline hot spots are effective for in vitro antibody affinity maturation. JF - Journal of Biological Chemistry AU - Ho, M AU - Kreitman, R J AU - Onda, M AU - Pastan, I AD - Laboratory of Molecular Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 607 EP - 617 VL - 280 IS - 1 SN - 0021-9258, 0021-9258 KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - N 14025:RNA/DNA role in infection & immune response KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17637261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=In+Vitro+Antibody+Evolution+Targeting+Germline+Hot+Spots+to+Increase+Activity+of+an+Anti-CD22+Immunotoxin&rft.au=Ho%2C+M%3BKreitman%2C+R+J%3BOnda%2C+M%3BPastan%2C+I&rft.aulast=Ho&rft.aufirst=M&rft.date=2005-01-01&rft.volume=280&rft.issue=1&rft.spage=607&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.M409783200 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1074/jbc.M409783200 ER - TY - JOUR T1 - Polymorphisms in the DNA nucleotide excision repair genes and lung cancer risk in Xuan Wei, China AN - 17590984; 6399107 AB - The lung cancer mortality rate in Xuan Wei County is among the highest in China and has been attributed to exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision repair (NER) plays a key role in reversing DNA damage from exposure to environmental carcinogens, such as PAHs, that form bulky DNA adducts. We studied single nucleotide polymorphisms (SNPs) and their corresponding haplotypes in 6 genes (ERCC1, ERCC2/XPD, ERCC4/XPF, ERCC5/XPG, RAD23B and XPC) involved in NER in a population-based case-control study of lung cancer in Xuan Wei. A total of 122 incident primary lung cancer cases and 122 individually matched controls were enrolled. Three linked SNPs in ERCC2 were associated with lung cancer with similar ORs; e.g. persons with the Gln allele at codon 751 had a 60% reduction of lung cancer (OR = 0.40, 95% CI 0.18-0.89). Moreover, one haplotype in ERCC2 was associated with a decreased risk of lung cancer (OR = 0.40, 95% CI 0.19- 0.85) compared to the most common haplotype. In addition, subjects with one or 2 copies of the Val allele at codon 249 of RAD23B had a 2-fold increased risk of lung cancer (OR = 1.91, 95% CI 1.12-3.24). In summary, our results suggest that genetic variants in genes involved in the NER pathway may play a role in lung cancer susceptibility in Xuan Wei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and in other populations with substantial environmental exposure to PAHs. JF - International Journal of Cancer AU - Shen, Min AU - Berndt, Sonja I AU - Rothman, Nathaniel AU - DeMarini, David M AU - Mumford, Judy L AU - He, Xingzhou AU - Bonner, Matthew R AU - Tian, Linwei AU - Yeager, Meredith AU - Welch, Robert AU - Chanock, Stephen AU - Zheng, Tongzhang AU - Caporaso, Neil AU - Lan, Qing AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, shenmi@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 768 EP - 773 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 116 IS - 5 SN - 0020-7136, 0020-7136 KW - Risk Abstracts; Oncogenes & Growth Factors Abstracts KW - Gene polymorphism KW - Indoor air pollution KW - Pollution effects KW - Carcinogens KW - Coal KW - Genetics KW - Nucleotide excision repair KW - Haplotypes KW - Lung cancer KW - DNA adducts KW - Mortality KW - Polycyclic aromatic hydrocarbons KW - DNA repair KW - DNA damage KW - Single-nucleotide polymorphism KW - Codons KW - China, People's Rep. KW - B 26248:DNA repair KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17590984?accountid=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=Polymorphisms+in+the+DNA+nucleotide+excision+repair+genes+and+lung+cancer+risk+in+Xuan+Wei%2C+China&rft.au=Shen%2C+Min%3BBerndt%2C+Sonja+I%3BRothman%2C+Nathaniel%3BDeMarini%2C+David+M%3BMumford%2C+Judy+L%3BHe%2C+Xingzhou%3BBonner%2C+Matthew+R%3BTian%2C+Linwei%3BYeager%2C+Meredith%3BWelch%2C+Robert%3BChanock%2C+Stephen%3BZheng%2C+Tongzhang%3BCaporaso%2C+Neil%3BLan%2C+Qing&rft.aulast=Shen&rft.aufirst=Min&rft.date=2005-01-01&rft.volume=116&rft.issue=5&rft.spage=768&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.21117 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - China, People's Rep.; Indoor air pollution; Pollution effects; Genetics; Polycyclic aromatic hydrocarbons; Mortality; Lung cancer; Haplotypes; Single-nucleotide polymorphism; Codons; Nucleotide excision repair; DNA damage; Coal; Gene polymorphism; Carcinogens; DNA adducts; DNA repair DO - http://dx.doi.org/10.1002/ijc.21117 ER - TY - JOUR T1 - Production of Recombinant Protein Using the HeLa S3-Vaccinia Virus Expression System: Bioreactor Perfusion and Effects of Post-Infection Temperature AN - 17576888; 6433336 AB - Adaptation of the vaccinia virus expression system to HeLa S3 suspension bioreactor culture for the production of recombinant protein was conducted. Evaluation of hollow fiber perfusion of suspension culture demonstrated its potential for increased cell density prior to infection. The hollow fiber was also used for medium manipulations prior to infection. Two process parameters, multiplicity of infection (MOI) and temperature during the protein production phase, were evaluated to determine their effect on expression of the reporter protein, enhanced green fluorescent protein (EGFP). An MOI of 1.0 was sufficient for infection and led to the highest level of intracellular EGFP expression. Reducing the temperature to 34 not equal to during the protein production phase increased production of the protein two-fold compared to 37 not equal to in spinner flask culture. Scaling up the process to a 1.5-liter bioreactor with hollow fiber perfusion led to an overall production level of 9.9 mu g EGFP/10 super(6) infected cells, or 27 mg EGFP per liter. JF - Bioscience, Biotechnology, and Biochemistry AU - Bleckwenn, Nicole A AU - Bentley, William E AU - Shiloach, Joseph AD - Biotechnology Unit, NIDDK, National Institutes of Health Y1 - 2005 PY - 2005 DA - 2005 SP - 1065 EP - 1072 PB - Japan Society for Bioscience, Biotechnology, and Agrochemistry - Nippon Nogeikagaku Kai, 2-4-16 Yayoi bunkyo-ku Tokyo 113-0032 Japan, [URL:http://www.jsbba.or.jp] VL - 69 IS - 6 SN - 0916-8451, 0916-8451 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Temperature effects KW - Fibers KW - Perfusion KW - Vaccinia virus KW - Bioreactors KW - Cell density KW - Green fluorescent protein KW - Suspension culture KW - Cell culture KW - Multiplicity of infection KW - Scaling KW - W3 33580:Process engineering KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17576888?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioscience%2C+Biotechnology%2C+and+Biochemistry&rft.atitle=Production+of+Recombinant+Protein+Using+the+HeLa+S3-Vaccinia+Virus+Expression+System%3A+Bioreactor+Perfusion+and+Effects+of+Post-Infection+Temperature&rft.au=Bleckwenn%2C+Nicole+A%3BBentley%2C+William+E%3BShiloach%2C+Joseph&rft.aulast=Bleckwenn&rft.aufirst=Nicole&rft.date=2005-01-01&rft.volume=69&rft.issue=6&rft.spage=1065&rft.isbn=&rft.btitle=&rft.title=Bioscience%2C+Biotechnology%2C+and+Biochemistry&rft.issn=09168451&rft_id=info:doi/10.1271%2Fbbb.69.1065 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccinia virus; Temperature effects; Bioreactors; Fibers; Perfusion; Cell culture; Multiplicity of infection; Cell density; Suspension culture; Scaling; Green fluorescent protein DO - http://dx.doi.org/10.1271/bbb.69.1065 ER - TY - JOUR T1 - The stabilizing contribution of thymine in duplexes of (dA) sub(24) with (dU) sub(24), (dT) sub(24), (dU sub(12)-dT sub(12)), (dU-dT) sub(12), (dU sub(2)-dT sub(2)) sub(6), or (dU sub(3)-dT sub(3)) sub(4): Nearest neighbor and next-nearest neighbor effects AN - 17555645; 6262552 AB - Ultraviolet melting curves are used to determine the effect of the pyrimidine 5-methyl group on the stability of duplexes of (dA) sub(24) with (dU) sub(24), (dT) sub(24), (dU sub(12)-dT sub(12)), (dU-dT) sub(12), (dU sub(2)- dT sub(2)) sub(6), and (dU sub(3)-dT sub(3)) sub(4). Substitution of a T for a U results in an increase in stability, which is attributed to an increase in strength of dipole-induced dipole and dispersion (van der Waals) interactions. Significant additional enhancement occurs when two T residues are adjacent. A further increase in the number of adjacent T's has a relatively slight effect on T sub(m). The sequence effect appears to be largely attributable to an increment in dispersion forces. The CD spectra of the duplexes are all closely similar except in the region between 260 and 290 nm. A band near 272 nm associated with the presence of U in the spectrum of (dA) sub(24).(dU) sub(24) decreases in intensity when T's are incorporated in the pyrimidine strand. The band is completely replaced in the spectrum of (dA) sub(24).(dT) sub(24) with a new maximum at 282 nm and a minimum at 268 nm, both of lower magnitude. The emergence of the two new bands is correlated with the presence of adjacent T's once more, and only two adjacent T's appear necessary for a major part of the change to occur. The degree of cation release on thermal dissociation of the oligomer dimers ranges from [Delta]i = 0.14 to 0.16, about the same or slightly less than values reported for polynucleotide duplexes and less than predicted from theoretical calculations. JF - Biopolymers AU - Howard, Frank B AD - Laboratory of Molecular Biology, NIDDK, NIH, Bethesda, MD 20892, FrankH@intra.niddk.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 221 EP - 229 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 78 IS - 4 SN - 0006-3525, 0006-3525 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Melting KW - U.V. radiation KW - Cations KW - Biopolymers KW - pyrimidines KW - polynucleotides KW - Thymine KW - W4 330:Biopolymers & Food Biotechnology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17555645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biopolymers&rft.atitle=The+stabilizing+contribution+of+thymine+in+duplexes+of+%28dA%29+sub%2824%29+with+%28dU%29+sub%2824%29%2C+%28dT%29+sub%2824%29%2C+%28dU+sub%2812%29-dT+sub%2812%29%29%2C+%28dU-dT%29+sub%2812%29%2C+%28dU+sub%282%29-dT+sub%282%29%29+sub%286%29%2C+or+%28dU+sub%283%29-dT+sub%283%29%29+sub%284%29%3A+Nearest+neighbor+and+next-nearest+neighbor+effects&rft.au=Howard%2C+Frank+B&rft.aulast=Howard&rft.aufirst=Frank&rft.date=2005-01-01&rft.volume=78&rft.issue=4&rft.spage=221&rft.isbn=&rft.btitle=&rft.title=Biopolymers&rft.issn=00063525&rft_id=info:doi/10.1002%2Fbip.20289 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - pyrimidines; U.V. radiation; polynucleotides; Thymine; Cations; Melting; Biopolymers DO - http://dx.doi.org/10.1002/bip.20289 ER - TY - JOUR T1 - A census of membrane-bound and intracellular signal transduction proteins in bacteria: Bacterial IQ, extroverts and introverts AN - 17540429; 6412007 AB - Background: Analysis of complete microbial genomes showed that intracellular parasites and other microorganisms that inhabit stable ecological niches encode relatively primitive signaling systems, whereas environmental microorganisms typically have sophisticated systems of environmental sensing and signal transduction. Results: This paper presents results of a comprehensive census of signal transduction proteins - histidine kinases, methyl-accepting chemotaxis receptors, Ser/Thr/Tyr protein kinases, adenylate and diguanylate cyclases and c-di-GMP phosphodiesterases - encoded in 167 bacterial and archaeal genomes, sequenced by the end of 2004. The data have been manually checked to avoid false-negative and false-positive hits that commonly arise during large-scale automated analyses and compared against other available resources. The census data show uneven distribution of most signaling proteins among bacterial and archaeal phyla. The total number of signal transduction proteins grows approximately as a square of genome size. While histidine kinases are found in representatives of all phyla and are distributed according to the power law, other signal transducers are abundant in certain phylogenetic groups but virtually absent in others. Conclusions: The complexity of signaling systems differs even among closely related organisms. Still, it usually can be correlated with the phylogenetic position of the organism, its lifestyle, and typical environmental challenges it encounters. The number of encoded signal transducers (or their fraction in the total protein set) can be used as a measure of the organism's ability to adapt to diverse conditions, the 'bacterial IQ', while the ratio of transmembrane receptors to intracellular sensors can be used to define whether the organism is an 'extrovert', actively sensing the environmental parameters, or an 'introvert', more concerned about its internal homeostasis. Some of the microorganisms with the highest IQ, including the current leader Wolinella succinogenes, are found among the poorly studied beta-, delta- and epsilon-proteobacteria. Among all bacterial phyla, only cyanobacteria appear to be true introverts, probably due to their capacity to conduct oxygenic photosynthesis, using a complex system of intracellular membranes. The census data, available at http://www.ncbi.nlm.nih.gov/Complete_Genomes/SignalCensus.html, can be used to get an insight into metabolic and behavioral propensities of each given organism and improve prediction of the organism's properties based solely on its genome sequence. JF - BMC Microbiology AU - Galperin, MY AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 5 KW - Microbiology Abstracts B: Bacteriology KW - Phylogeny KW - Histidine kinase KW - Genomes KW - Intracellular signalling KW - Photosynthesis KW - Nucleotide sequence KW - Niches KW - Homeostasis KW - Wolinella succinogenes KW - Chemotaxis KW - Protein kinase KW - Census KW - phosphodiesterase KW - Adenylate cyclase KW - Signal transduction KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17540429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Microbiology&rft.atitle=A+census+of+membrane-bound+and+intracellular+signal+transduction+proteins+in+bacteria%3A+Bacterial+IQ%2C+extroverts+and+introverts&rft.au=Galperin%2C+MY&rft.aulast=Galperin&rft.aufirst=MY&rft.date=2005-01-01&rft.volume=5&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Microbiology&rft.issn=1471-2180&rft_id=info:doi/10.1186%2F1471-2180-5-35 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Wolinella succinogenes; Signal transduction; Census; Genomes; Histidine kinase; Phylogeny; Protein kinase; phosphodiesterase; Adenylate cyclase; Homeostasis; Photosynthesis; Niches; Nucleotide sequence; Chemotaxis; Intracellular signalling DO - http://dx.doi.org/10.1186/1471-2180-5-35 ER - TY - JOUR T1 - An adaptive method for cDNA microarray normalization AN - 17529305; 6234358 AB - Background: Normalization is a critical step in analysis of gene expression profiles. For dual-labeled arrays, global normalization assumes that the majority of the genes on the array are non-differentially expressed between the two channels and that the number of over-expressed genes approximately equals the number of under-expressed genes. These assumptions can be inappropriate for custom arrays or arrays in which the reference RNA is very different from the experimental samples. Results: We propose a mixture model based normalization method that adaptively identifies non-differentially expressed genes and thereby substantially improves normalization for dual-labeled arrays in settings where the assumptions of global normalization are problematic. The new method is evaluated using both simulated and real data. Conclusions: The new normalization method is effective for general microarray platforms when samples with very different expression profile are co-hybridized and for custom arrays where the majority of genes are likely to be differentially expressed. JF - BMC Bioinformatics AU - Zhao, Yingdong AU - Li, Ming-Chung AU - Simon, Richard AD - Biometric Research Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA, zhaoy@helix.nih.gov Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 6 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Gene expression KW - Mathematical models KW - RNA KW - Bioinformatics KW - DNA microarrays KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17529305?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Bioinformatics&rft.atitle=An+adaptive+method+for+cDNA+microarray+normalization&rft.au=Zhao%2C+Yingdong%3BLi%2C+Ming-Chung%3BSimon%2C+Richard&rft.aulast=Zhao&rft.aufirst=Yingdong&rft.date=2005-01-01&rft.volume=6&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Bioinformatics&rft.issn=1471-2105&rft_id=info:doi/10.1186%2F1471-2105-6-28 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene expression; DNA microarrays; RNA; Mathematical models; Bioinformatics DO - http://dx.doi.org/10.1186/1471-2105-6-28 ER - TY - JOUR T1 - askMEDLINE: a free-text, natural language query tool for MEDLINE/PubMed AN - 17523444; 6215701 AB - Background: Plain language search tools for MEDLINE/PubMed are few. We wanted to develop a search tool that would allow anyone using a free-text, natural language query and without knowing specialized vocabularies that an expert searcher might use, to find relevant citations in MEDLINE/PubMed. This tool would translate a question into an efficient search. Results: The accuracy and relevance of retrieved citations were compared to references cited in BMJ POEMs and CATs (critically appraised topics) questions from the University of Michigan Department of Pediatrics. askMEDLINE correctly matched the cited references 75.8% in POEMs and 89.2 % in CATs questions on first pass. When articles that were deemed to be relevant to the clinical questions were included, the overall efficiency in retrieving journal articles was 96.8% (POEMs) and 96.3% (CATs.) Conclusions: askMEDLINE might be a useful search tool for clinicians, researchers, and other information seekers interested in finding current evidence in MEDLINE/PubMed. The text-only format could be convenient for users with wireless handheld devices and those with low-bandwidth connections in remote locations. JF - BMC Medical Informatics and Decision Making AU - Fontelo, Paul AU - Liu, Fang AU - Ackerman, Michael AD - Office of High Performance Computing and Communications, National Library of Medicine, 8600 Rockville Pike, Bethesda, Maryland 20894, USA, fontelo@nlm.nih.gov Y1 - 2005 PY - 2005 DA - 2005 PB - BioMed Central Ltd., Middlesex House 34-42 Cleveland Street London W1T 4LB UK, [mailto:info@biomedcentral.com], [URL:http://www.biomedcentral.com] VL - 5 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Decision making KW - Pediatrics 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/17523444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMC+Medical+Informatics+and+Decision+Making&rft.atitle=askMEDLINE%3A+a+free-text%2C+natural+language+query+tool+for+MEDLINE%2FPubMed&rft.au=Fontelo%2C+Paul%3BLiu%2C+Fang%3BAckerman%2C+Michael&rft.aulast=Fontelo&rft.aufirst=Paul&rft.date=2005-01-01&rft.volume=5&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=BMC+Medical+Informatics+and+Decision+Making&rft.issn=1472-6947&rft_id=info:doi/10.1186%2F1472-6947-5-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Language; Pediatrics; Decision making; Bioinformatics DO - http://dx.doi.org/10.1186/1472-6947-5-5 ER - TY - JOUR T1 - Reproductive and hormonal factors and risk of brain tumors in adult females AN - 17520572; 6152163 AB - Causes of brain tumors are largely unknown, and there is an urgent need to identify possible risk factors. Several observations point to a possible role of reproductive hormones, but few epidemiologic studies have examined whether reproductive factors, such as age at menarche and parity, are associated with brain tumor risk. We conducted a multi-center case-control study of newly diagnosed glioma (n = 212) and meningioma (n = 151) and frequency-matched controls (n = 436) in women from hospitals in Phoenix, Arizona; Boston, Massachusetts; and Pittsburgh, Pennsylvania between 1994 and 1998. Research nurses interviewed patients regarding potential risk factors for brain tumors, including reproductive factors and hormone use. Unconditional logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Risk of glioma increased with older age at menarche [OR = 1.90 (95% CI = 1.09-3.32) for age at menarche =>14 vs. <12 years]. Early age at first birth was associated with reduced risk of glioma [OR = 0.43 (95% CI = 0.23-0.83) for a first birth before age 20 vs. nulliparity], but there was little effect of number of births. Exogenous hormone use was also associated with a lower risk of glioma, but risks did not vary systematically according to duration of use or age at first use. Possibly owing to low statistical power, there were few noteworthy associations between meningioma and reproductive factors, other than a nonsignificant (p = 0.09) trend of increasing risk with increasing age at menopause. The findings suggest that hormonal exposures early in life may be associated with risk of glioma, but the evidence is inconsistent and does not point clearly to a specific causal or protective hypothesis. JF - International Journal of Cancer AU - Hatch, Elizabeth E AU - Linet, Martha S AU - Zhang, Jianying AU - Fine, Howard A AU - Shapiro, William R AU - Selker, Robert G AU - Black, Peter M AU - Inskip, Peter D AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, MD, USA, eehatch@bu.edu Y1 - 2005 PY - 2005 DA - 2005 SP - 797 EP - 805 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 114 IS - 5 SN - 0020-7136, 0020-7136 KW - tumors KW - Risk Abstracts; Oncogenes & Growth Factors Abstracts KW - Age KW - USA, Massachusetts KW - Brain KW - Adults KW - Tumors KW - Hormones KW - USA, Pennsylvania KW - USA, Arizona KW - Reproduction KW - Glioma KW - Females KW - meningioma KW - Menopause KW - R2 23060:Medical and environmental health KW - B 26225:Steroid hormone receptors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17520572?accountid=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=Reproductive+and+hormonal+factors+and+risk+of+brain+tumors+in+adult+females&rft.au=Hatch%2C+Elizabeth+E%3BLinet%2C+Martha+S%3BZhang%2C+Jianying%3BFine%2C+Howard+A%3BShapiro%2C+William+R%3BSelker%2C+Robert+G%3BBlack%2C+Peter+M%3BInskip%2C+Peter+D&rft.aulast=Hatch&rft.aufirst=Elizabeth&rft.date=2005-01-01&rft.volume=114&rft.issue=5&rft.spage=797&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.20776 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA, Pennsylvania; USA, Massachusetts; USA, Arizona; Menopause; Age; Reproduction; Hormones; Brain; Tumors; Adults; Females; Glioma; meningioma DO - http://dx.doi.org/10.1002/ijc.20776 ER - TY - JOUR T1 - Family history as a co-factor for adenocarcinoma and squamous cell carcinoma of the uterine cervix: Results from two studies conducted in Costa Rica and the United States AN - 17496823; 6271091 AB - Previous work suggests that cervical cancer may aggregate in families. We evaluated the association between a family history of gynecological tumors and risk of squamous cell and adenocarcinomas of the cervix in 2 studies conducted in Costa Rica and the United States. The Costa Rican study consisted of 2,073 women (85 diagnosed with CIN3 or cancer, 55 diagnosed with CIN2 and 1,933 controls) selected from a population-based study of 10,049 women. The U.S. study consisted of 570 women (124 with in situ or invasive adenocarcinomas, 139 with in situ or invasive squamous cell carcinomas of the cervix and 307 community- based controls) recruited as part of a multicentric case-control study in the eastern part of the United States. Information on family history of cervical and other cancers among first-degree relatives was ascertained via questionnaire. Information on other risk factors for cervical cancer was obtained via questionnaire. Human papillomavirus (HPV) exposure was assessed in both studies using broad spectrum HPV L1-based PCR testing of exfoliated cervicovaginal cells and in Costa Rica by additional testing of plasma collected from participants for antibodies against the L1 protein of HPV types 16, 18, 31 and 45 by ELISA. A family history of cervical cancer in a first-degree relative was associated with increased risk of squamous tumors in both studies (odds ration [OR] = 3.2 for CIN3/cancer vs. controls; 95% confidence interval [CI] = 1.1-9.4 in Costa Rica; OR = 2.6 for in situ/invasive squamous cell carcinoma cases vs. controls, 95% CI = 1.1-6.4 in the Eastern United States study). These associations were evident regardless of whether the affected relative was a mother, sister or daughter of the study participant. Furthermore, observed effects were not strongly modified by age. In Costa Rica, the effect persisted in analysis restricted to HPV- exposed individuals (OR = 3.0; 95% CI = 1.0-9.0), whereas in the Eastern United States study there was evidence of attenuation of risk in analysis of squamous carcinoma cases restricted to HPV positive women (OR = 1.4; 95% CI = 0.29-6.6). No significant association was observed between a family history of cervical cancer in a first-degree relative and adenocarcinomas (OR = 1.3; 95% CI = 0.43- 3.9). History of gynecological tumors other than cervical cancer in a first- degree relative was not significantly associated with risk of disease in either study. These results are consistent with a role of host factors in the pathogenesis of squamous cell cervical cancer, although familial aggregation due to shared environmental exposures cannot be ruled out. JF - International Journal of Cancer AU - Zelmanowicz, Alice de M AU - Schiffman, Mark AU - Herrero, Rolando AU - Goldstein, Alisa M AU - Sherman, Mark E AU - Burk, Robert D AU - Gravitt, Patti AU - Viscidi, Ray AU - Schwartz, Peter AU - Barnes, Willard AU - Mortel, Rodrigue AU - Silverberg, Steven G AU - Buckland, Julie AU - Hildesheim, Allan AD - Programa de Pos-graduacAo em Epidemiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, Hildesha@exchange.nih.gov Y1 - 2005 PY - 2005 DA - 2005 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 116 IS - 4 SN - 0020-7136, 0020-7136 KW - cervix KW - Risk Abstracts KW - Genetics KW - Historical account KW - USA KW - Costa Rica KW - Cancer KW - Family studies KW - Human papillomavirus KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17496823?accountid=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=Family+history+as+a+co-factor+for+adenocarcinoma+and+squamous+cell+carcinoma+of+the+uterine+cervix%3A+Results+from+two+studies+conducted+in+Costa+Rica+and+the+United+States&rft.au=Zelmanowicz%2C+Alice+de+M%3BSchiffman%2C+Mark%3BHerrero%2C+Rolando%3BGoldstein%2C+Alisa+M%3BSherman%2C+Mark+E%3BBurk%2C+Robert+D%3BGravitt%2C+Patti%3BViscidi%2C+Ray%3BSchwartz%2C+Peter%3BBarnes%2C+Willard%3BMortel%2C+Rodrigue%3BSilverberg%2C+Steven+G%3BBuckland%2C+Julie%3BHildesheim%2C+Allan&rft.aulast=Zelmanowicz&rft.aufirst=Alice+de&rft.date=2005-01-01&rft.volume=116&rft.issue=4&rft.spage=&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.21048 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human papillomavirus; USA; Costa Rica; Cancer; Historical account; Family studies; Genetics DO - http://dx.doi.org/10.1002/ijc.21048 ER - TY - JOUR T1 - The interactive online SKY/M-FISH & CGH Database and the Entrez Cancer Chromosomes search database: Linkage of chromosomal aberrations with the genome sequence AN - 17496526; 6271071 AB - To catalog data on chromosomal aberrations in cancer derived from emerging molecular cytogenetic techniques and to integrate these data with genome maps, we have established two resources, the NCI and N SKY/M-FISH & CGH Database and the Cancer Chromosomes database. The goal of the former is to allow investigators to submit and analyze clinical and research cytogenetic data. It contains a karyotype parser tool, which automatically converts the ISCN short- form karyotype into an internal representation displayed in detailed form and as a colored ideogram with band overlay, and also has a tool to compare CGH profiles from multiple cases. The Cancer Chromosomes database integrates the SKY/M-FISH & CGH Database with the Mitelman Database of Chromosome Aberrations in Cancer and the Recurrent Chromosome Aberrations in Cancer database. These three datasets can now be searched seamlessly by use of the Entrez search and retrieval system for chromosome aberrations, clinical data, and reference citations. Common diagnoses, anatomic sites, chromosome breakpoints, junctions, numerical and structural abnormalities, and bands gained and lost among selected cases can be compared by use of the "similarity" report. Because the model used for CGH data is a subset of the karyotype data, it is now possible to examine the similarities between CGH results and karyotypes directly. All chromosomal bands are directly linked to the Entrez Map Viewer database, providing integration of cytogenetic data with the sequence assembly. These resources, developed as a part of the Cancer Chromosome Aberration Project (CCAP) initiative, aid the search for new cancer-associated genes and foster insights into the causes and consequences of genetic alterations in cancer. Published 2005 Wiley-Liss, Inc. JF - Genes, Chromosomes and Cancer AU - Knutsen, Turid AU - Gobu, Vasuki AU - Knaus, Rodger AU - Padilla-Nash, Hesed AU - Augustus, Meena AU - Strausberg, Robert L AU - Kirsch, Ilan R AU - Sirotkin, Karl AU - Ried, Thomas AD - Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, knutsent@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 52 EP - 64 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 44 IS - 1 SN - 1045-2257, 1045-2257 KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Genomes KW - Catalogs KW - Nucleotide sequence KW - Karyotypes KW - Cancer KW - Models KW - Integration KW - Breakpoints KW - Databases KW - Chromosomes KW - Chromosome aberrations KW - Gene mapping KW - G 07470:Cytogenetics & general KW - W3 33080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17496526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+Chromosomes+and+Cancer&rft.atitle=The+interactive+online+SKY%2FM-FISH+%26amp%3B+CGH+Database+and+the+Entrez+Cancer+Chromosomes+search+database%3A+Linkage+of+chromosomal+aberrations+with+the+genome+sequence&rft.au=Knutsen%2C+Turid%3BGobu%2C+Vasuki%3BKnaus%2C+Rodger%3BPadilla-Nash%2C+Hesed%3BAugustus%2C+Meena%3BStrausberg%2C+Robert+L%3BKirsch%2C+Ilan+R%3BSirotkin%2C+Karl%3BRied%2C+Thomas&rft.aulast=Knutsen&rft.aufirst=Turid&rft.date=2005-01-01&rft.volume=44&rft.issue=1&rft.spage=52&rft.isbn=&rft.btitle=&rft.title=Genes%2C+Chromosomes+and+Cancer&rft.issn=10452257&rft_id=info:doi/10.1002%2Fgcc.20224 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Databases; Cancer; Chromosome aberrations; Chromosomes; Karyotypes; Genomes; Models; Nucleotide sequence; Breakpoints; Gene mapping; Integration; Catalogs DO - http://dx.doi.org/10.1002/gcc.20224 ER - TY - JOUR T1 - Nonmelanoma skin cancer in relation to ionizing radiation exposure among U.S. radiologic technologists AN - 17495625; 6247674 AB - Ionizing radiation (IR) is an established cause of nonmelanoma skin cancer, but there is uncertainty about the risk associated with chronic occupational exposure to IR and how it is influenced by ultraviolet radiation (UVR) exposure. We studied 1,355 incident cases with basal cell carcinoma (BCC) and 270 with squamous cell carcinoma (SCC) of the skin in a cohort of 65,304 U.S. white radiologic technologists who responded to the baseline questionnaire survey in 1983-1989 and the follow-up survey in 1994-1998. Cox's proportional-hazards model was used to estimate relative risks of BCC and SCC associated with surrogate measures of occupational exposure to IR and residential UVR exposure during childhood and adulthood, adjusted for potential confounders including pigmentation characteristics. Relative risks of BCC, but not of SCC, were elevated among technologists who first worked during the 1950s (RR = 1.42; 95% CI = 1.12-1.80), 1940s (RR = 2.04; 95% CI = 1.44-2.88) and before 1940 (RR = 2.16; 95% CI = 1.14-4.09), when IR exposures were high, compared to those who first worked after 1960 (p for trend < 0.01). The effect of year first worked on BCC risk was not modified by UVR exposure, but was significantly stronger among individuals with lighter compared to darker eye and hair color (p = 0.013 and 0.027, respectively). This study provides some evidence that chronic occupational exposure to IR at low to moderate levels can increase the risk of BCC, and that this risk may be modified by pigmentation characteristics. JF - International Journal of Cancer AU - Yoshinaga, Shinji AU - Hauptmann, Michael AU - Sigurdson, Alice J AU - Doody, Michele Morin AU - Freedman, DMichal AU - Alexander, Bruce H AU - Linet, Martha S AU - Ron, Elaine AU - Mabuchi, Kiyohiko AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA, yosinaga@nirs.go.jp Y1 - 2005 PY - 2005 DA - 2005 SP - 828 EP - 834 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 115 IS - 5 SN - 0020-7136, 0020-7136 KW - Risk Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Eye KW - Skin cancer KW - U.V. radiation KW - Ultraviolet radiation KW - Occupational exposure KW - Pigmentation KW - Skin KW - squamous cell carcinoma KW - Children KW - Hair KW - Cancer KW - Color KW - Basal cells KW - USA KW - Ionizing radiation KW - R2 23080:Industrial and labor KW - H 8000:Radiation Safety/Electrical Safety KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17495625?accountid=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=Nonmelanoma+skin+cancer+in+relation+to+ionizing+radiation+exposure+among+U.S.+radiologic+technologists&rft.au=Yoshinaga%2C+Shinji%3BHauptmann%2C+Michael%3BSigurdson%2C+Alice+J%3BDoody%2C+Michele+Morin%3BFreedman%2C+DMichal%3BAlexander%2C+Bruce+H%3BLinet%2C+Martha+S%3BRon%2C+Elaine%3BMabuchi%2C+Kiyohiko&rft.aulast=Yoshinaga&rft.aufirst=Shinji&rft.date=2005-01-01&rft.volume=115&rft.issue=5&rft.spage=828&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.20939 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA; Occupational exposure; Skin; Cancer; Pigmentation; Ionizing radiation; Ultraviolet radiation; Risk assessment; Skin cancer; Basal cells; Color; Eye; squamous cell carcinoma; Hair; U.V. radiation; Children DO - http://dx.doi.org/10.1002/ijc.20939 ER - TY - JOUR T1 - International patterns and trends in testis cancer incidence AN - 17491089; 6247673 AB - Although the incidence of testis cancer has risen markedly in many Western populations over the past half-century, it is not clear whether rates in other populations also have increased. To clarify this issue, we examined testis cancer incidence rates over the 25-year time period of 1973-1997 for selected populations around the world. Age-standardized incidence rates for 21 registries in the Americas, Asia, Europe and Oceania over successive 5-year time periods were obtained from volumes 4-8 of Cancer Incidence in Five Continents. Testis cancer rates rose between 1973 and 1997 in most populations worldwide, although the increases were strongest and most consistent among populations of European ancestry. Rates appear to be leveling off in some populations. The increases in testis cancer remain unexplained, although changes in the prevalence of important risk factors for this disease may be responsible. Published 2005 Wiley-Liss, Inc. JF - International Journal of Cancer AU - Purdue, Mark P AU - Devesa, Susan S AU - Sigurdson, Alice J AU - McGlynn, Katherine A AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA, purduem@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 822 EP - 827 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 115 IS - 5 SN - 0020-7136, 0020-7136 KW - testes KW - Risk Abstracts KW - Europe KW - Population dynamics KW - Cancer KW - Ethnic groups KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17491089?accountid=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=International+patterns+and+trends+in+testis+cancer+incidence&rft.au=Purdue%2C+Mark+P%3BDevesa%2C+Susan+S%3BSigurdson%2C+Alice+J%3BMcGlynn%2C+Katherine+A&rft.aulast=Purdue&rft.aufirst=Mark&rft.date=2005-01-01&rft.volume=115&rft.issue=5&rft.spage=822&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.20931 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Europe; Population dynamics; Ethnic groups; Cancer DO - http://dx.doi.org/10.1002/ijc.20931 ER - TY - JOUR T1 - A cis-acting sequence involved in chromosome segregation in Escherichia coli AN - 17488763; 6230046 AB - Eukaryotic chromosomes contain a locus, the centromere, at which force is applied to separate replicated chromosomes. A centromere analogue is also found in some bacterial plasmids and chromosomes, although not yet identified in the well-studied Escherichia coli chromosome. We aimed to identify centromere-like sequences in E. coli with the premise that such sequences would be the first to migrate towards the cell poles, away from the cell centre where DNA replication is believed to occur. We have labelled different loci on the chromosome by integrating arrays of binding sites for LacI-EYFP and phage lambda cI-ECFP and supplying these fusion proteins in trans. Comparison of such pairs of loci suggests the presence of a centromere-like site close to the origin of replication. Polar migration of the site was dependent on migS, a locus recently implicated in chromosome migration, thus providing strong support for migS being the E. coli centromere. JF - Molecular Microbiology AU - Fekete, Richard A AU - Chattoraj, Dhruba K AD - Laboratory of Biochemistry, CCR, NCI, NIH, Bldg. 37, Bethesda, MD 20892-4255, USA, chattord@mail.nih.gov Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 175 EP - 183 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 55 IS - 1 SN - 0950-382X, 0950-382X KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Phages KW - DNA biosynthesis KW - Replication KW - Nucleotide sequence KW - Plasmids KW - Centromeres KW - Chromosomes KW - Replication origins KW - Escherichia coli KW - Fusion protein KW - Cell migration KW - N 14030:DNA: biosynthesis, repair & replication cycle KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17488763?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=A+cis-acting+sequence+involved+in+chromosome+segregation+in+Escherichia+coli&rft.au=Fekete%2C+Richard+A%3BChattoraj%2C+Dhruba+K&rft.aulast=Fekete&rft.aufirst=Richard&rft.date=2005-01-01&rft.volume=55&rft.issue=1&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04392.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Figures, 6; tables, 1; references, 32. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Chromosomes; Centromeres; Replication; Cell migration; Replication origins; Plasmids; Fusion protein; Phages; Nucleotide sequence; DNA biosynthesis DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04392.x ER - TY - JOUR T1 - Low level, long-term inorganic arsenite exposure causes generalized resistance to apoptosis in cultured human keratinocytes: Potential role in skin co-carcinogenesis AN - 17484424; 6247227 AB - Inorganic arsenic is a human carcinogen that targets the skin. Carcinogenesis is a multistep process in which acquired apoptotic resistance is a common event and prior work in non-skin cells shows acquired resistance to apoptosis occurs with chronic arsenite exposure. In the present study, when HaCaT cells, an immortalized, non-tumorigenic human keratinocyte cell line, were continuously exposed to low-level inorganic arsenite (as sodium arsenite; 100 nM) for 28 weeks, the cells acquired a generalized resistance to apoptosis. This included resistance to apoptosis induced by acute high concentrations of arsenite, ultraviolet A (UVA) irradiation, and several chemotherapeutic compounds (cisplatin, etoposide and doxorubicin). These arsenite-tolerant (As- TL) cells showed similar levels of UVA-induced reactive oxygen species (ROS) and oxidative DNA damage when compared to passage match control cells. Because cellular apoptosis is dependent on the balance between proapoptotic and survival pathways, the roles of protein kinase B (PKB), a key antiapoptotic molecule, in this acquired apoptotic resistance were investigated. Stimulation of apoptosis markedly decreased nuclear phosphorylated PKB (P-PKB) levels in control cells, but As-TL cells showed greatly increased stability of nuclear P-PKB. Pretreatment of the As-TL cells with LY294002 or Wortmannin, which specifically inhibit PKB phosphorylation, completely blocked apoptotic resistance in As-TL cells, indicating acquired apoptotic resistance is associated with increased stability of nuclear P-PKB. Because arsenic and UV irradiation are co- carcinogenic in mouse skin, resistance to UV-induced apoptosis in As-TL cells may allow UV-damaged cells to escape normal cell population controls and initiate the carcinogenic cascade. The observation that As-TL cells show no lessening of UV-induced genotoxicity supports this possibility. JF - International Journal of Cancer AU - Pi, Jingbo AU - He, Yuying AU - Bortner, Carl AU - Huang, Jianli AU - Liu, Jie AU - Zhou, Tong AU - Qu, Wei AU - North, Susan L AU - Kasprzak, Kazimierz S AU - Diwan, Bhalchandra A AU - Chignell, Colin F AU - Waalkes, Michael P AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA, waalkes@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 20 EP - 26 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 116 IS - 1 SN - 0020-7136, 0020-7136 KW - Toxicology Abstracts KW - Cell survival KW - Arsenic KW - Sodium arsenite KW - Skin KW - Apoptosis KW - Genotoxicity KW - Arsenite KW - Carcinogens KW - Doxorubicin KW - DNA damage KW - U.V. radiation KW - Reactive oxygen species KW - Cisplatin KW - Phosphorylation KW - Carcinogenesis KW - AKT protein KW - Protein kinase KW - Keratinocytes KW - Etoposide KW - Wortmannin KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17484424?accountid=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+Cancer&rft.atitle=Low+level%2C+long-term+inorganic+arsenite+exposure+causes+generalized+resistance+to+apoptosis+in+cultured+human+keratinocytes%3A+Potential+role+in+skin+co-carcinogenesis&rft.au=Pi%2C+Jingbo%3BHe%2C+Yuying%3BBortner%2C+Carl%3BHuang%2C+Jianli%3BLiu%2C+Jie%3BZhou%2C+Tong%3BQu%2C+Wei%3BNorth%2C+Susan+L%3BKasprzak%2C+Kazimierz+S%3BDiwan%2C+Bhalchandra+A%3BChignell%2C+Colin+F%3BWaalkes%2C+Michael+P&rft.aulast=Pi&rft.aufirst=Jingbo&rft.date=2005-01-01&rft.volume=116&rft.issue=1&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.20990 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Apoptosis; Arsenite; Skin; Keratinocytes; Arsenic; U.V. radiation; Sodium arsenite; Carcinogens; DNA damage; Phosphorylation; AKT protein; Wortmannin; Doxorubicin; Carcinogenesis; Cell survival; Cisplatin; Genotoxicity; Etoposide; Protein kinase; Reactive oxygen species DO - http://dx.doi.org/10.1002/ijc.20990 ER - TY - JOUR T1 - Higher magnitude accumbal phasic firing changes among core neurons exhibiting tonic firing increases during cocaine self-administration AN - 17452568; 6644641 AB - Studies using i.v. cocaine self-administration in rats have documented rapid-phasic changes in the firing rate of nucleus accumbens neurons within seconds of cocaine-reinforced lever presses, as well as changes that occur over the course of the cocaine self-administration experiment, i.e. tonic changes in firing rate. During the self-administration period of the experiment, individual neurons exhibit either a tonic increase, a tonic decrease, or no tonic change in firing rate, relative to the neuron's firing rate during the pre-drug period. We evaluated whether rapid-phasic changes in firing were differentially associated with tonically reduced or tonically elevated firing of nucleus accumbens core and shell neurons in cocaine self-administering rats. Rapid-phasic firing patterns within seconds of the cocaine-reinforced lever press were exhibited predominantly by core neurons that also exhibited tonic increases in firing. Conversely, core neurons that did not exhibit such rapid- phasic firing patterns were more likely to show tonically reduced firing. Moreover, core neurons were more likely than shell neurons to exhibit: 1) tonic increases in firing and 2) rapid-phasic increases in firing preceding the cocaine-reinforced lever press. These differences between accumbens subterritories may be related to their distinct involvement in operant responding; the present findings are consistent with an emerging literature which implicates shell in contextual stimulus-induced responding, and core in processing the instrumental response via its discrete output to classic basal ganglia structures. The distinct tendency of the core to exhibit increased firing, coupled with its dichotomous firing outputs (i.e. tonic decreases without rapid phasic responses or tonic increases with rapid phasic responses), may reflect particular sensitivity of these neurons to excitatory limbic afferent signaling involved in instrumental responding. Enhanced phasic responsivity in the core may be an integral component of the mechanism inherent in normal reward processing which is subverted by chronic drug exposure. JF - Neuroscience AU - Ghitza, U E AU - Prokopenko, V F AU - West, MO AU - Fabbricatore, A T AD - Behavioral Neuroscience, Clinical Pharmacology and Therapeutics Research Branches, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, tonio@rci.rutgers.edu Y1 - 2005 PY - 2005 DA - 2005 SP - 1075 EP - 1085 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 137 IS - 3 SN - 0306-4522, 0306-4522 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - addiction KW - electrophysiology KW - reward KW - motivation KW - conditioned KW - ventral striatum KW - Nucleus accumbens KW - Neurons KW - Reinforcement KW - Self-administration KW - Cocaine KW - Drug abuse KW - Firing pattern KW - Basal ganglia KW - Drug self-administration KW - Signal transduction 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/17452568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Higher+magnitude+accumbal+phasic+firing+changes+among+core+neurons+exhibiting+tonic+firing+increases+during+cocaine+self-administration&rft.au=Ghitza%2C+U+E%3BProkopenko%2C+V+F%3BWest%2C+MO%3BFabbricatore%2C+A+T&rft.aulast=Ghitza&rft.aufirst=U&rft.date=2005-01-01&rft.volume=137&rft.issue=3&rft.spage=1075&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/10.1016%2Fj.neuroscience.2005.10.026 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Nucleus accumbens; Neurons; Reinforcement; Self-administration; Drug abuse; Cocaine; Firing pattern; Basal ganglia; Signal transduction; Drug self-administration DO - http://dx.doi.org/10.1016/j.neuroscience.2005.10.026 ER - TY - JOUR T1 - Statistical Criteria in fMRI Studies of Multisensory Integration AN - 17434218; 6538887 AB - Inferences drawn from functional magnetic resonance imaging (fMRI) studies are depen-dent on the statistical criteria used to define different brain regions as "active" or "inactive" under the experimental manipulation. In fMRI studies of multisensory integration, additional criteria are used to classify a subset of the active brain regions as "multisensory." Because there is no general agreement in the literature on the optimal criteria for performing this classification, we investigated the effects of seven different multisensory statistical criteria on a single test dataset collected as human subjects performed auditory, visual, and auditory--visual object recognition. Activation maps created using the different criteria differed dramatically. The classification of the superior temporal sulcus (STS) was used as a performance measure, because a large body of converging evidence demonstrates that the STS is important for auditory-visual integration. A commonly proposed criterion, "supra-additivity" or "super-additivity", which requires the multisensory response to be larger than the summed unisensory responses, did not classify STS as multisensory. Alternative criteria, such as requiring the multisensory response to be larger than the maximum or the mean of the unisensory responses, successfully classified STS as multisensory. This practical demonstration strengthens theoretical arguments that the super-additivity is not an appropriate criterion for all studies of multisensory integration. Moreover, the importance of examining evoked fMRI responses, whole brain activation maps, maps from multiple individual subjects, and mixed-effect group maps are discussed in the context of selecting statistical criteria. JF - Neuroinformatics AU - Beauchamp AD - Laboratory of Brain and Cognition, National Institute of Mental Health Intramural Research Program, National institutes of Health, Department of Health and Human Services, Bethesda, MD, USA Y1 - 2005 PY - 2005 DA - 2005 SP - 93 EP - 114 VL - 3 IS - 2 SN - 1539-2791, 1539-2791 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Brain mapping KW - Statistics KW - Functional magnetic resonance imaging KW - Brain KW - Pattern recognition KW - superior temporal sulcus KW - Classification KW - Sensory integration KW - Bioinformatics KW - N3 11004:Motor & sensory systems KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17434218?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroinformatics&rft.atitle=Statistical+Criteria+in+fMRI+Studies+of+Multisensory+Integration&rft.au=Beauchamp&rft.aulast=Beauchamp&rft.aufirst=&rft.date=2005-01-01&rft.volume=3&rft.issue=2&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Neuroinformatics&rft.issn=15392791&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Functional magnetic resonance imaging; Sensory integration; Statistics; Brain mapping; Classification; Brain; Bioinformatics; superior temporal sulcus; Pattern recognition ER - TY - JOUR T1 - The Rcs Phosphorelay: A Complex Signal Transduction System AN - 17422482; 6537888 AB - RcsC, RcsB, and RcsA were first identified as a sensor kinase, a response regulator, and an auxiliary regulatory protein, respectively, regulating the genes of capsular polysaccharide synthesis. Recent advances have demonstrated that these proteins are part of a complex phosphorelay, in which phosphate travels from the histidine kinase domain in RcsC to a response regulator domain in the same protein; from there to a phosphotransfer protein, RcsD; and from there to RcsB. In addition to capsule synthesis, which requires the unstable regulatory protein RcsA, RcsB also stimulates transcription of a small RNA, RprA; the cell division gene ftsZ; and genes encoding membrane and periplasmic proteins, including the osmotically inducible genes osmB and osmC. The Rcs system appears to play an important role in the later stages of biofilm development; induction of Rcs signaling by surfaces is consistent with this role. JF - Annual Review of Microbiology AU - Majdalani, N AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA, susang@helix.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 379 EP - 405 VL - 59 SN - 0066-4227, 0066-4227 KW - Rcs protein KW - Microbiology Abstracts B: Bacteriology KW - Histidine kinase KW - Cell division KW - regulatory proteins KW - Phosphate KW - Reviews KW - Transcription KW - Developmental stages KW - Biofilms KW - Polysaccharides KW - Signal transduction KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17422482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annual+Review+of+Microbiology&rft.atitle=The+Rcs+Phosphorelay%3A+A+Complex+Signal+Transduction+System&rft.au=Majdalani%2C+N%3BGottesman%2C+S&rft.aulast=Majdalani&rft.aufirst=N&rft.date=2005-01-01&rft.volume=59&rft.issue=&rft.spage=379&rft.isbn=&rft.btitle=&rft.title=Annual+Review+of+Microbiology&rft.issn=00664227&rft_id=info:doi/10.1146%2Fannurev.micro.59.050405.101230 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Histidine kinase; Cell division; Phosphate; regulatory proteins; Reviews; Developmental stages; Transcription; Biofilms; Polysaccharides; Signal transduction DO - http://dx.doi.org/10.1146/annurev.micro.59.050405.101230 ER - TY - JOUR T1 - alpha -Particle Radioimmunotherapy of Disseminated Peritoneal Disease Using a super(212)Pb-Labeled Radioimmunoconjugate Targeting HER2 AN - 17418043; 6537241 AB - These studies demonstrate the feasibility of targeted therapy for the treatment of disseminated peritoneal disease using super(212)Pb-labeled Herceptin as an in vivo generator of super(212)Bi. In vitro studies compare the potential of the bismuth radioisotopes, super(213)Bi and super(212)Bi, to that of super(212)Pb. Overall, super(212)Pb results in a higher therapeutic index than either bismuth radioisotope, requiring lower radioactivity ( mu Ci) for effective cytotoxic response. A pilot radioimmunotherapy (RIT) experiment treating mice bearing 5 d LS-174T intraperitoneally (i.p.) xenografts determined a maximum tolerated dose (MTD) of 20-40 mu Ci with i.p. administration. A specific dose response was observed and 10 mu Ci was selected as the effective operating dose for future experiments. Median survival of tumor-bearing mice receiving 10 mu Ci increased from 19 to 56 days (p = 0.008). The efficacy of super(212)Pb- Herceptin was also assessed in a human pancreatic carcinoma xenograft (Shaw; i.p.) animal model previously reported as unresponsive to super(213)Bi- Herceptin (p = 0.002). Multiple dosing of super(212)Pb-Herceptin was evaluated in both animal models. The median survival of mice bearing 3 d LS-174T i.p. xenografts increased to 110 days, with up to 3 doses of super(212)Pb-Herceptin given at approximately monthly intervals; however, there was no evidence of a correlation with the second and third doses (p = 0.98). No improvement in median survival was noted with a similar regimen in the Shaw xenograft model. JF - Cancer Biotherapy and Radiopharmaceuticals AU - Milenic, DE AU - Garmestani, K AU - Brady, ED AU - Albert, P S AU - Ma, D AU - Abdulla, A AU - Brechbiel, M W AD - National Institutes of Health; 10 Center Drive, MSC-1088, Building 10, Room 1B40, Bethesda, MD 20892, USA, dm71q@nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 557 EP - 559 VL - 20 IS - 5 SN - 1084-9785, 1084-9785 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Cytotoxicity KW - Pancreatic carcinoma KW - ErbB-2 protein KW - Radioisotopes KW - Animal models KW - Survival KW - Radioactivity KW - Peritoneal diseases KW - Xenografts KW - Immunoconjugates KW - Lead KW - W3 33160:Antibody based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17418043?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Biotherapy+and+Radiopharmaceuticals&rft.atitle=alpha+-Particle+Radioimmunotherapy+of+Disseminated+Peritoneal+Disease+Using+a+super%28212%29Pb-Labeled+Radioimmunoconjugate+Targeting+HER2&rft.au=Milenic%2C+DE%3BGarmestani%2C+K%3BBrady%2C+ED%3BAlbert%2C+P+S%3BMa%2C+D%3BAbdulla%2C+A%3BBrechbiel%2C+M+W&rft.aulast=Milenic&rft.aufirst=DE&rft.date=2005-01-01&rft.volume=20&rft.issue=5&rft.spage=557&rft.isbn=&rft.btitle=&rft.title=Cancer+Biotherapy+and+Radiopharmaceuticals&rft.issn=10849785&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Xenografts; Survival; Animal models; Peritoneal diseases; Radioisotopes; Pancreatic carcinoma; Radioactivity; Cytotoxicity; Lead; Immunoconjugates; ErbB-2 protein ER - TY - JOUR T1 - Altered brain tissue composition in heavy marijuana users AN - 17415074; 6539411 AB - Marijuana is the most widely used illicit substance in the United States; however, previous imaging studies have not detected altered brain structure in marijuana users compared to non-users. Voxel-based morphometry was used to investigate possible differences in brain tissue composition in a group of 11 heavy marijuana users and a group of 8 non-users. All participants were male. Statistical comparisons were made at the voxel level on T1-weighted magnetic resonance images to determine differences in gray matter and white matter tissue density. Compared to non-users, marijuana users had lower gray matter density in a cluster of voxels in the right parahippocampal gyrus (P = 0.0001), and greater density bilaterally near the precentral gyrus and the right thalamus (P < 0.04). Marijuana users also had lower white matter density in the left parietal lobe (P = 0.03), and higher density around the parahippocampal and fusiform gyri on the left side compared to non-users (P < 0.002). Longer duration of marijuana use (in years) was significantly correlated with higher white matter tissue density in the left precentral gyrus (P = 0.045). Our preliminary results suggest evidence of possible structural differences in the brain of heavy marijuana users, and localize regions for further investigation of the effects of marijuana in the brain. JF - Drug and Alcohol Dependence AU - Matochik, JA AU - Eldreth, DA AU - Cadet, J-L AU - Bolla, KI AD - Intramural Research Program, Neuroimaging Research Branch, National Institute on Drug Abuse, NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224-6823, USA Y1 - 2005/01// PY - 2005 DA - Jan 2005 SP - 23 EP - 30 VL - 77 IS - 1 SN - 0376-8716, 0376-8716 KW - Toxicology Abstracts KW - Neuroimaging KW - Statistics KW - Magnetic resonance imaging KW - Brain KW - Substantia alba KW - Drug abuse KW - Thalamus KW - Cannabis KW - parahippocampal gyrus KW - Parietal lobe KW - precentral gyrus KW - Substantia grisea KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17415074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+Alcohol+Dependence&rft.atitle=Altered+brain+tissue+composition+in+heavy+marijuana+users&rft.au=Matochik%2C+JA%3BEldreth%2C+DA%3BCadet%2C+J-L%3BBolla%2C+KI&rft.aulast=Matochik&rft.aufirst=JA&rft.date=2005-01-01&rft.volume=77&rft.issue=1&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Drug+and+Alcohol+Dependence&rft.issn=03768716&rft_id=info:doi/10.1016%2Fj.drugalcdep.2004.06.011 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Neuroimaging; Statistics; Magnetic resonance imaging; Brain; Cannabis; parahippocampal gyrus; Substantia alba; Drug abuse; Parietal lobe; Thalamus; Substantia grisea; precentral gyrus DO - http://dx.doi.org/10.1016/j.drugalcdep.2004.06.011 ER - TY - JOUR T1 - The eIF1A C-terminal domain promotes initiation complex assembly, scanning and AUG selection in vivo AN - 17386012; 6496125 AB - Translation initiation factor 1A stimulates 40S-binding of the eukaryotic initiation factor 2 (eIF2)/GTP/Met-tRNA sub(i) super(Met) ternary complex (TC) and promotes scanning in vitro. eIF1A contains an OB-fold present in bacterial IF1 plus N- and C-terminal extensions. Truncating the C-terminus ([Delta]C) or mutating OB-fold residues (66-70) of eIF1A reduced general translation in vivo but increased GCN4 translation (Gcd super(-) phenotype) in a manner suppressed by overexpressing TC. Consistent with this, both mutations diminished 40S-bound TC, eIF5 and eIF3 in vivo, and [Delta]C impaired TC recruitment in vitro. The assembly defects of the OB-fold mutation can be attributed to reduced 40S-binding of eIF1A, whereas [Delta]C impairs eIF1A function on the ribosome. A substitution in the C-terminal helix (98- 101) also reduced 43S assembly in vivo. Rather than producing a Gcd super(-) phenotype, however, 98-101 impairs GCN4 derepression in a manner consistent with defective scanning by reinitiating ribosomes. Indeed, 98- 101 allows formation of aberrant 48S complexes in vitro and increases utilization of non-AUG codons in vivo. Thus, the OB-fold is crucial for ribosome-binding and the C-terminal domain of eIF1A has eukaryotic-specific functions in TC recruitment and scanning. JF - EMBO Journal AU - Fekete, Christie A AU - Applefield, Drew J AU - Blakely, Stephen A AU - Shirokikh, Nikolay AU - Pestova, Tatyana AU - Lorsch, Jon R AU - Hinnebusch, Alan G AD - Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA, ahinnebusch@nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 3588 EP - 3601 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 24 IS - 20 SN - 0261-4189, 0261-4189 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - eIF1A KW - eIF2 KW - GCN4 KW - scanning KW - translation KW - Initiation factors KW - Initiation complex KW - Scanning KW - Translation initiation KW - Recruitment KW - C-Terminus KW - Derepression KW - Codons KW - GTP KW - Ribosomes KW - Mutation KW - J 02410:Animal Diseases KW - N 14050:Post-transcriptional regulation and other UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17386012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EMBO+Journal&rft.atitle=The+eIF1A+C-terminal+domain+promotes+initiation+complex+assembly%2C+scanning+and+AUG+selection+in+vivo&rft.au=Fekete%2C+Christie+A%3BApplefield%2C+Drew+J%3BBlakely%2C+Stephen+A%3BShirokikh%2C+Nikolay%3BPestova%2C+Tatyana%3BLorsch%2C+Jon+R%3BHinnebusch%2C+Alan+G&rft.aulast=Fekete&rft.aufirst=Christie&rft.date=2005-01-01&rft.volume=24&rft.issue=20&rft.spage=3588&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/10.1038%2Fsj.emboj.7600821 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Initiation factors; Initiation complex; Scanning; Translation initiation; C-Terminus; Recruitment; Codons; Derepression; GTP; Ribosomes; Mutation DO - http://dx.doi.org/10.1038/sj.emboj.7600821 ER - TY - JOUR T1 - The perceived onset of dieting and loss of control eating behaviors in overweight children AN - 17367593; 6432775 AB - The current study investigated the self-reported temporal relationships of dieting, binge eating, and overweight in childhood. One hundred five non- treatment-seeking overweight children ages 6-13 years were interviewed with the children's Eating Disorder Examination (ChEDE) and queried regarding dieting, loss of control (LOC) eating, and overweight history. Questionnaires of depressive symptoms, trait anxiety, and parent-reported problems were completed. Sixty percent of the children reported having attempted at least one diet. These children had higher ChEDE scores (global, p < .001), greater body mass index (BMI) and body fat mass (p <= .001), and a trend towards an earlier reported age of overweight onset (p = .06) compared with children who had never dieted. The 29.5% of children who reported LOC eating had significantly higher ChEDE scores (global, p < .001), ineffectiveness, negative self-esteem, and externalizing scores (all ps < .05) compared with those who had never experienced LOC eating. Most children reported becoming overweight before either dieting (79.4%) or experiencing LOC eating (63.6%). Among the 25.7% reporting both dieting and LOC eating, two thirds reported LOC eating before dieting. Participants who reported dieting before overweight had higher negative mood scores (p < .01). Children reporting dieting before LOC eating had higher ChEDE Weight Concern (p < .01) and global (p < .05) scores. For overweight, non- treatment-seeking children, both dieting and LOC eating are common. Dieting precedes the development of LOC eating only one third of the time, but is associated with greater disordered eating cognitions. The relationship between childhood-onset dieting and LOC eating in overweight children requires further investigation to determine the causal pathways for the subsequent development of eating disorders. JF - International Journal of Eating Disorders AU - Tanofsky-Kraff, Marian AU - Faden, Dara AU - Yanovski, Susan Z AU - Wilfley, Denise E AU - Yanovski, Jack A AD - Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, tanofskm@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 112 EP - 122 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 38 IS - 2 SN - 0276-3478, 0276-3478 KW - Physical Education Index KW - middle childhood KW - overweight KW - dieting KW - loss of control KW - binge eating KW - Obesity KW - Age KW - Anxiety KW - Eating disorders KW - Body mass KW - Diet (weight control) KW - Surveys KW - Health (history) KW - Children KW - Cognition KW - Evaluation KW - Moods KW - Trends KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17367593?accountid=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=International+Journal+of+Eating+Disorders&rft.atitle=The+perceived+onset+of+dieting+and+loss+of+control+eating+behaviors+in+overweight+children&rft.au=Tanofsky-Kraff%2C+Marian%3BFaden%2C+Dara%3BYanovski%2C+Susan+Z%3BWilfley%2C+Denise+E%3BYanovski%2C+Jack+A&rft.aulast=Tanofsky-Kraff&rft.aufirst=Marian&rft.date=2005-01-01&rft.volume=38&rft.issue=2&rft.spage=112&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Eating+Disorders&rft.issn=02763478&rft_id=info:doi/10.1002%2Feat.20158 LA - English DB - Physical Education Index N1 - Date revised - 2006-12-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Obesity; Age; Anxiety; Eating disorders; Body mass; Diet (weight control); Health (history); Surveys; Children; Cognition; Evaluation; Moods; Trends DO - http://dx.doi.org/10.1002/eat.20158 ER - TY - JOUR T1 - Linking tumor cell cytotoxicity to mechanism of drug action: An integrated analysis of gene expression, small-molecule screening and structural databases AN - 17323350; 6221466 AB - An integrated, bioinformatic analysis of three databases comprising tumor- cell-based small molecule screening data, gene expression measurements, and PDB (Protein Data Bank) ligand-target structures has been developed for probing mechanism of drug action (MOA). Clustering analysis of GI sub(50) profiles for the NCI's database of compounds screened across a panel of tumor cells (NCI sub(60)) was used to select a subset of unique cytotoxic responses for about 4000 small molecules. Drug-gene-PDB relationships for this test set were examined by correlative analysis of cytotoxic response and differential gene expression profiles within the NCI sub(60) and structural comparisons with known ligand- target crystallographic complexes. A survey of molecular features within these compounds finds thirteen conserved Compound Classes, each class exhibiting chemical features important for interactions with a variety of biological targets. Protein targets for an additional twelve Compound Classes could be directly assigned using drug-protein interactions observed in the crystallographic database. Results from the analysis of constitutive gene expressions established a clear connection between chemo-resistance and overexpression of gene families associated with the extracellular matrix, cytoskeletal organization, and xenobiotic metabolism. Conversely, chemo- sensitivity implicated overexpression of gene families involved in homeostatic functions of nucleic acid repair, aryl hydrocarbon metabolism, heat shock response, proteasome degradation and apoptosis. Correlations between chemo- responsiveness and differential gene expressions identified chemotypes with nonselective (i.e. many) molecular targets from those likely to have selective (i.e. few) molecular targets. Applications of data mining strategies that jointly utilize tumor cell screening, genomic, and structural data are presented for hypotheses generation and identifying novel anticancer candidates. Proteins 2005. Published 2005 Wiley-Liss, Inc. JF - Proteins: Structure, Function & Bioinformatics AU - Covell, David G AU - Wallqvist, Anders AU - Huang, Ruili AU - Thanki, Narmada AU - Rabow, Alfred A AU - Lu, Xiang-Jun AD - National Cancer Institute-Frederick, Developmental Therapeutics Program, Screening Technologies Branch, Laboratory of Computational Technologies, Frederick, Maryland, covell@ncifcrf.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 403 EP - 433 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 59 IS - 3 SN - 0887-3585, 0887-3585 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/17323350?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteins%3A+Structure%2C+Function+%26+Bioinformatics&rft.atitle=Linking+tumor+cell+cytotoxicity+to+mechanism+of+drug+action%3A+An+integrated+analysis+of+gene+expression%2C+small-molecule+screening+and+structural+databases&rft.au=Covell%2C+David+G%3BWallqvist%2C+Anders%3BHuang%2C+Ruili%3BThanki%2C+Narmada%3BRabow%2C+Alfred+A%3BLu%2C+Xiang-Jun&rft.aulast=Covell&rft.aufirst=David&rft.date=2005-01-01&rft.volume=59&rft.issue=3&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=Proteins%3A+Structure%2C+Function+%26+Bioinformatics&rft.issn=08873585&rft_id=info:doi/10.1002%2Fprot.20392 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1002/prot.20392 ER - TY - JOUR T1 - Comparing Participants' Rating and Compendium Coding to Estimate Physical Activity Intensities AN - 17314146; 6199730 AB - This study assessed agreement between participants' rating (PMET) and compendium coding (CMET) of estimating physical activity intensity in a population of older minority women. As part of the Women on the Move study, 224 women completed a 7-day activity diary and wore an accelerometer for 7 days. All activities recorded were coded using PMET and CMET methodologies. MET-mins were computed for total activity in 10 activity dimensions (MET = metabolic equivalent, where 1 MET is the amount of energy expended at rest). Results revealed that correlations between the two methods were high (ranging from .81 to .98) but the means were significantly different (p < .05) for total activity and for 7 of the 10 activity dimensions. In general, MET-mins based on PMET were higher than those based on CMET, and agreement between methods was low (ranging from .26 to .31). Revising the MET values assigned to PMET improved agreement with CMET. Accelerometer MET-mins were significantly associated with total activity for both methods; however, their correlations were low. Agreement with accelerometer MET-mins was low and was similar for revised PMET and CMET. The revised participants' rating provides an alternative method to rank individuals because it provides similar results to the compendium coding; however, neither method accurately estimates accelerometer MET-mins. JF - Measurement in Physical Education and Exercise Science AU - Maasse, L C AU - Eason, KE AU - Tortolero AU - Kelder, SH AD - Health Promotion Research Branch, Division of Cancer Control and Population Sciences, 6130 Executive Blvd., EPN 4080, MSC 7335, Bethesda, MD 20892-7335, USA, massel@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 1 EP - 20 VL - 9 IS - 1 SN - 1091-367X, 1091-367X KW - Physical Education Index KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17314146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Measurement+in+Physical+Education+and+Exercise+Science&rft.atitle=Comparing+Participants%27+Rating+and+Compendium+Coding+to+Estimate+Physical+Activity+Intensities&rft.au=Maasse%2C+L+C%3BEason%2C+KE%3BTortolero%3BKelder%2C+SH&rft.aulast=Maasse&rft.aufirst=L&rft.date=2005-01-01&rft.volume=9&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Measurement+in+Physical+Education+and+Exercise+Science&rft.issn=1091367X&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-02-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Investigation of nontypeable Haemophilus influenzae outer membrane protein P6 as a new carrier for lipooligosaccharide conjugate vaccines AN - 17246244; 6972828 AB - Nontypeable Haemophilus influenzae (NTHi) outer membrane protein P6 was used as a new protein carrier for NTHi detoxified lipooligosaccharide (dLOS) conjugates due to its conservation and potential to elicit bactericidal antibodies. P6 was covalently conjugated to dLOS of strain 9274 through adipic acid dihydrazide with different ratios of dLOS to P6, which resulted in two conjugate formulations with weight ratios of dLOS to P6 of 3.7 for dLOS-P6 (I) and 1.6 for dLOS-P6 (II). Binding activity of the conjugates was examined by an enzyme-linked immunosorbent assay with mouse monoclonal antibodies specific to LOS and P6 and a rabbit anti-P6 serum. The results showed that the conjugates bound not only to the LOS antibody but also to both P6 antibodies, suggesting that the conjugates retained epitopes of both LOS and P6 antigens. Animal studies revealed that dLOS-P6 (II) induced high levels of anti-LOS and anti-P6 IgGs in mice and rabbits. However, dLOS-P6 (I) induced lower levels of anti-LOS IgGs in mice and rabbits and anti-P6 IgGs in rabbits with no anti-P6 IgGs in mice. In addition, all rabbit, but not mouse, antisera elicited by the conjugates showed bactericidal activity against the homologous strain, and two of them elicited by each conjugate plus Ribi adjuvant showed cross-bactericidal activity against three of five major serotype stains. These data indicate that P6 could serve as an effective carrier for dLOS or other carbohydrate conjugates and that the ratio of carbohydrate to P6 might contribute to immune responses in vivo. JF - Vaccine AU - Wu, Tinghuai AU - Chen, Jing AU - Murphy, Timothy F AU - Green, Bruce A AU - Gu, Xin-Xing AD - Vaccine Research Section, National Institute on Deafness and Other Communication Disorders, Rockville, MD, USA, guxx@nidcd.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 5177 EP - 5185 PB - Butterworth-Heinemann, 313 Washington St. Newton MA 02158 USA VL - 23 IS - 44 SN - 0264-410X, 0264-410X KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts B: Bacteriology; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Serotypes KW - outer membrane proteins KW - Stains KW - Adjuvants KW - Adipic acid dihydrazide KW - Carbohydrates KW - Bactericidal activity KW - Epitopes KW - Enzyme-linked immunosorbent assay KW - Haemophilus influenzae KW - Monoclonal antibodies KW - Lipooligosaccharides KW - Antisera KW - Immunoglobulin G KW - Vaccines KW - F 06100:Vaccines - active immunity KW - J 02350:Immunology KW - W 30965:Miscellaneous, Reviews KW - W3 33360:Adjuvants and carriers UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17246244?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Investigation+of+nontypeable+Haemophilus+influenzae+outer+membrane+protein+P6+as+a+new+carrier+for+lipooligosaccharide+conjugate+vaccines&rft.au=Wu%2C+Tinghuai%3BChen%2C+Jing%3BMurphy%2C+Timothy+F%3BGreen%2C+Bruce+A%3BGu%2C+Xin-Xing&rft.aulast=Wu&rft.aufirst=Tinghuai&rft.date=2005-01-01&rft.volume=23&rft.issue=44&rft.spage=5177&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2Fj.vaccine.2005.06.014 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Haemophilus influenzae; Immunoglobulin G; outer membrane proteins; Vaccines; Carbohydrates; Lipooligosaccharides; Adipic acid dihydrazide; Serotypes; Enzyme-linked immunosorbent assay; Adjuvants; Antisera; Bactericidal activity; Monoclonal antibodies; Stains; Epitopes DO - http://dx.doi.org/10.1016/j.vaccine.2005.06.014 ER - TY - JOUR T1 - Prenatal diethylstilbestrol (DES) exposure is associated with uterine leiomyoma development AN - 17240512; 6976182 AB - Early life exposure to DES causes uterine leiomyomata in laboratory animals. We examined the relationship between prenatal DES exposure and development of uterine leiomyomata in women. Among randomly selected study participants (819 black women, 504 white women), leiomyoma status was determined by ultrasound screening (70%) or surgical record review (7%). We relied on self-report of prior diagnosis in 13%. Leiomyoma status could not be ascertained for 10% and they were excluded from analyses. Prenatal DES exposure was assessed by interview. All five of the black women who reported DES exposure had leiomyomata. Among white women, 76% who reported prenatal DES exposure had leiomyomata compared with 52% of the unexposed (adjusted odds ratio for whites: 2.4; 95% confidence interval CI: 1.1-5.4). Exposed women tended to have larger tumors. Results were robust to sensitivity analyses. Findings support experimental animal data and indicate a role for prenatal estrogen exposure in the etiology of human uterine leiomyoma. JF - Reproductive Toxicology AU - Baird, Donna Day AU - Newbold, Retha AD - Epidemiology Branch, A3-05, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, Research Triangle Park, NC 27709, USA, baird@niehs.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 81 EP - 84 PB - Elsevier Science Inc., Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 20 IS - 1 SN - 0890-6238, 0890-6238 KW - diethylstilbestrol KW - Health & Safety Science Abstracts; Toxicology Abstracts KW - Diethylstilbestrol KW - Prenatal exposure KW - Uterine leiomyoma KW - Uterine fibroids KW - Epidemiology KW - Environmental estrogens KW - Endocrine disrupters KW - Uterus KW - Estrogens KW - Etiology KW - Prenatal experience KW - Laboratory testing KW - Laboratory animals KW - Tumors KW - Reviews KW - Females KW - Ultrasound KW - Toxicology KW - Ethnic groups KW - estrogens KW - X 24310:Pharmaceuticals KW - H 14000:Toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17240512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Reproductive+Toxicology&rft.atitle=Prenatal+diethylstilbestrol+%28DES%29+exposure+is+associated+with+uterine+leiomyoma+development&rft.au=Baird%2C+Donna+Day%3BNewbold%2C+Retha&rft.aulast=Baird&rft.aufirst=Donna&rft.date=2005-01-01&rft.volume=20&rft.issue=1&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Reproductive+Toxicology&rft.issn=08906238&rft_id=info:doi/10.1016%2Fj.reprotox.2005.01.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Etiology; Estrogens; Uterus; Prenatal experience; Reviews; Laboratory animals; Tumors; Diethylstilbestrol; Ultrasound; Ethnic groups; Laboratory testing; Females; Toxicology; estrogens DO - http://dx.doi.org/10.1016/j.reprotox.2005.01.002 ER - TY - JOUR T1 - Transcallosal inhibition in chronic subcortical stroke AN - 17239860; 6968267 AB - Movements of the paretic hand in patients with chronic subcortical stroke are associated with high interhemispheric inhibition (IHI) targeting the motor cortex in the lesioned hemisphere relative to healthy controls. The purpose of this investigation was to determine whether this abnormality also involves IHI operating during movements of the non-paretic hand. Here, we studied IHI in the process of generation of voluntary index finger movements by the paretic and non-paretic hands in a simple reaction time paradigm in a group of patients with chronic subcortical stroke. With movements of the non-paretic index finger, IHI targeting the contralateral primary motor cortex ( sub(c)M1) decreased progressively to turn into facilitation at around movement onset, similar to healthy controls. In contrast, movements of the paretic index finger resulted in significantly deeper inhibition at all premovement timings relative to the non- paretic hand. In conclusion, these results document a deeper premovement IHI with paretic than non-paretic hand movements of patients with chronic subcortical stroke, a possible mechanism underlying deficits in motor control. JF - NeuroImage AU - Duque, Julie AU - Hummel, Friedhelm AU - Celnik, Pablo AU - Murase, Nagako AU - Mazzocchio, Riccardo AU - Cohen, Leonardo G AD - Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20817, USA, cohenl@ninds.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 940 EP - 946 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 28 IS - 4 SN - 1053-8119, 1053-8119 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts; Bioengineering Abstracts KW - Cortex (motor) KW - Cerebral hemispheres KW - Stroke KW - Hand KW - Corpus callosum KW - Finger KW - Reaction time task KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews KW - N3 11127:Cerebral blood flow and stroke UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17239860?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=NeuroImage&rft.atitle=Transcallosal+inhibition+in+chronic+subcortical+stroke&rft.au=Duque%2C+Julie%3BHummel%2C+Friedhelm%3BCelnik%2C+Pablo%3BMurase%2C+Nagako%3BMazzocchio%2C+Riccardo%3BCohen%2C+Leonardo+G&rft.aulast=Duque&rft.aufirst=Julie&rft.date=2005-01-01&rft.volume=28&rft.issue=4&rft.spage=940&rft.isbn=&rft.btitle=&rft.title=NeuroImage&rft.issn=10538119&rft_id=info:doi/10.1016%2Fj.neuroimage.2005.06.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-09-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hand; Stroke; Finger; Cortex (motor); Reaction time task; Cerebral hemispheres; Corpus callosum DO - http://dx.doi.org/10.1016/j.neuroimage.2005.06.033 ER - TY - JOUR T1 - Thyroid cancer and multiple primary tumors in the SEER cancer registries AN - 17231712; 6930585 AB - Thyroid cancer incidence rates have increased steadily in the United States and elsewhere. Radiation exposure at a young age is a strong risk factor, but otherwise the etiology is unclear. To explore etiologic clues, we studied the risk of thyroid cancer after an earlier primary cancer, as well as the risk of developing multiple primaries after an earlier thyroid cancer in the U.S. Surveillance, Epidemiology and End-Results (SEER) cancer registries program (1973-2000). In 2,036,597 patients diagnosed with any invasive cancer who survived for a minimum of 2 months, we observed a 42% increased risk compared to the general population for second thyroid cancer based on 1,366 cases (95% confidence interval (CI) = 35-50%; excess absolute risk (EAR) = 0.38/10,000 person-years (PY)). Elevated risks were observed after most cancer sites studied. The most pronounced excess (observed/expected (O/E) = 2.86) was seen for second thyroid cancers detected in the year after diagnosis of the first cancer. Among 29,456 2-month thyroid cancer survivors, 2,214 second cancers occurred (O/E = 1.11, 95% CI = 1.06-1.15; EAR = 7.64/10,000 PY). Again, the highest risk was seen in the first year (O/E = 1.26). Patients <40 years of age at diagnosis of thyroid cancer had a 39% increased risk of a second cancer, whereas for older patients the risk was elevated 6%. We observed consistently increased risks for cancers of the breast, prostate, and kidney, and a likely radiation treatment-related excess of leukemia. Based on small numbers of cases, cancers of the salivary glands, trachea, scrotum, adrenal glands, and brain and central nervous system (CNS) also occurred in excess. A decreased risk was observed for smoking-related malignancies. Thyroid cancer is associated with primary cancers of many different organs. Although enhanced medical surveillance likely plays a role, 2-way, positive associations between thyroid cancer and cancers of the breast, prostate, kidney, salivary glands, brain and CNS, scrotum, and leukemia suggest etiologic similarities and possible treatment effects. JF - International Journal of Cancer AU - Ronckers, Cecile M AU - McCarron, Peter AU - Ron, Elaine AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA, ronckerc@mail.nih.gov Y1 - 2005 PY - 2005 DA - 2005 SP - 281 EP - 288 PB - John Wiley & Sons, Inc., 111 River Street Hoboken NJ 07030 USA, [mailto:custserv@wiley.com], [URL:http://www.wiley.com/] VL - 117 IS - 2 SN - 0020-7136, 0020-7136 KW - Risk Abstracts KW - multiple primary cancers KW - thyroid cancer KW - epidemiology KW - radiotherapy KW - Leukemia KW - Central nervous system KW - USA KW - Etiology KW - Radiation KW - Epidemiology KW - Thyroid KW - Brain KW - Kidney KW - Cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17231712?accountid=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=Thyroid+cancer+and+multiple+primary+tumors+in+the+SEER+cancer+registries&rft.au=Ronckers%2C+Cecile+M%3BMcCarron%2C+Peter%3BRon%2C+Elaine&rft.aulast=Ronckers&rft.aufirst=Cecile&rft.date=2005-01-01&rft.volume=117&rft.issue=2&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2Fijc.21064 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-08-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Central nervous system; Leukemia; Etiology; Epidemiology; Radiation; Kidney; Brain; Thyroid; Cancer; USA DO - http://dx.doi.org/10.1002/ijc.21064 ER - TY - JOUR T1 - Classification of Proliferative Hepatocellular Lesions in Harlan Sprague-Dawley Rats Chronically Exposed to Dioxin-Like Compounds AN - 17095293; 6726032 AB - Over the years, the most appropriate classification scheme for nodular proliferative lesions of the hepatocyte has been heavily debated. In the most recent guidelines there appears to be a consensus for classifying these lesions as hepatocellular adenoma, hepatocellular carcinoma, or regenerative hyperplasia. Also, large foci of cellular alteration may appear somewhat nodular. Some nodular hepatocellular lesions from a group of 7 studies of dioxin and dioxin-like compounds conducted by the National Toxicology Program did not readily fit into these categories. Some of these lesions had morphologic features consistent with hyperplasia. However, there was not sufficient morphological or biological evidence to conclude that the entire response was regenerative. In other instances, these lesions had some features resembling adenoma, but contained a prominent component of biliary epithelium and/or oval cells. This component does not appear to be well described in the literature, and while its presence suggested a nodule to be nonneoplastic, this is inconclusive. This paper describes the morphology of these lesions, as well as the diagnostic approach taken in this series of studies. JF - Toxicologic Pathology AU - Hailey, J R AU - Walker, N J AU - Sells, D M AU - Brix, A E AU - Jokinen, M P AU - Nyska, A AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA Y1 - 2005 PY - 2005 DA - 2005 SP - 165 EP - 174 VL - 33 IS - 1 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - Hyperplasia KW - Hepatocytes KW - Epithelium KW - Adenoma KW - Dioxin KW - Nodules KW - Hepatocellular carcinoma KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17095293?accountid=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=Classification+of+Proliferative+Hepatocellular+Lesions+in+Harlan+Sprague-Dawley+Rats+Chronically+Exposed+to+Dioxin-Like+Compounds&rft.au=Hailey%2C+J+R%3BWalker%2C+N+J%3BSells%2C+D+M%3BBrix%2C+A+E%3BJokinen%2C+M+P%3BNyska%2C+A&rft.aulast=Hailey&rft.aufirst=J&rft.date=2005-01-01&rft.volume=33&rft.issue=1&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1080%2F01926230590888324 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-05-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Hyperplasia; Hepatocytes; Epithelium; Adenoma; Nodules; Dioxin; Hepatocellular carcinoma DO - http://dx.doi.org/10.1080/01926230590888324 ER - TY - JOUR T1 - Overview of the Molecular Biology of Hepatocellular Neoplasms and Hepatoblastomas of the Mouse Liver AN - 17094123; 6726033 AB - The molecular pathogenesis of chemically induced hepatocellular neoplasms and hepatoblastomas in the B6C3F1 mouse is unclear but may involve alterations in the beta -catenin/Wnt signaling pathway as was recently described for human liver neoplasms. The objectives of this research were to characterize the mutation frequency and spectrum of beta -catenin mutations and the intracellular localization of beta -catenin protein accumulation in chemically induced hepatoblastomas and hepatocellular neoplasms. In the majority of the hepatoblastomas examined by immunohistochemical methods, both nuclear and cytoplasmic localization of beta -catenin protein were detected, whereas in hepatocellular adenomas and carcinomas and normal liver only membrane staining was observed. Genomic DNA was isolated from paraffin sections of each liver tumor. beta -catenin exon 2 (corresponds to exon 3 in humans) genetic alterations were identified in the majority of hepatoblastomas from exposed mice. Deletion mutations were identified more frequently than point mutations in hepatoblastomas. Hepatocellular adenomas and carcinomas from treated mice had mutations in exon 2 of the beta -catenin gene which ranged from 32-43%, while 10% beta -catenin mutations were detected in spontaneous neoplasms. By immunohistochemical methods cyclin D1 was observed in most nuclei of hepatoblastomas and strong expression of cyclin D1 was confirmed by Western analysis regardless of treatment. The cumulative data suggests that beta -catenin mutations with upregulation of the beta -catenin protein and Wnt signaling most likely increased cyclin D1 expression. Cyclin D1 may provide an advantage during tumor progression of hepatocellular neoplasms and hepatoblastomas. The review will also focus on other genes which are important in mouse and human liver tumors. JF - Toxicologic Pathology AU - Kim, Y AU - Sills, R C AU - Houle, C D AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA Y1 - 2005 PY - 2005 DA - 2005 SP - 175 EP - 180 VL - 33 IS - 1 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - Deletion KW - Paraffin KW - Wnt protein KW - Exons KW - Point mutation KW - catenin KW - Reviews KW - Liver KW - DNA KW - genomics KW - Nuclei KW - Adenoma KW - Hepatocellular carcinoma KW - Signal transduction KW - cyclin D1 KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17094123?accountid=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=Overview+of+the+Molecular+Biology+of+Hepatocellular+Neoplasms+and+Hepatoblastomas+of+the+Mouse+Liver&rft.au=Kim%2C+Y%3BSills%2C+R+C%3BHoule%2C+C+D&rft.aulast=Kim&rft.aufirst=Y&rft.date=2005-01-01&rft.volume=33&rft.issue=1&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1080%2F01926230590522130 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-05-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Paraffin; Deletion; Wnt protein; Exons; Point mutation; catenin; Reviews; DNA; Liver; genomics; Nuclei; Adenoma; cyclin D1; Signal transduction; Hepatocellular carcinoma DO - http://dx.doi.org/10.1080/01926230590522130 ER - TY - JOUR T1 - Hormonal contraceptive use, pregnancy and parity, and the risk of cervical intraepithelial neoplasia 3 among oncogenic HPV DNA-positive women with equivocal or mildly abnormal cytology AN - 17093612; 6723828 AB - Oral contraceptive (OC) use, hormonal contraceptive use and multiparity are potential risk factors for cervical precancer, cervical intraepithelial neoplasia 3 (CIN3), but a limited number of studies have adequately accounted for possible confounding effect of oncogenic human papillomavirus (HPV) infection. To examine the relationships of these factors with CIN3, we conducted an analysis of women (n = 5,060) with minimally abnormal Pap smears who were enrolled in the ASCUS and LSIL Triage Study (ALTS), a clinical trial to evaluate management strategies. Cervical specimens collected at enrollment were tested for HPV DNA using 2 methods. Multivariate logistics regression models were used to assess associations (odds ratio [OR] with 95% confidence intervals [CI]) of the potential risk factors (e.g., OC use and parity) with testing oncogenic HPV positive among controls ( 1.0) and has a unique unpaired cysteine near the carboxy-terminus of the protein. The high catalytic efficiency of recombinant mEar 6 (k(cat)/K(m) = 0.9 x 10(6)/M/s) is similar to that of the cluster's closest human ortholog, eosinophil-derived neurotoxin (EDN/RNase 2). In summary, we have identified mEar 6 as one of only two RNase A superfamily ribonucleases known to be expressed specifically in response to pathophysiologic stress in vivo. JF - Genes and immunity AU - Nitto, T AU - Dyer, K D AU - Mejia, R A AU - Byström, J AU - Wynn, T A AU - Rosenberg, H F AD - Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, room 11N104, 9000 Rockville Pike, Bethesda, MD 20892, USA. tnitto@niaid.nih.gov Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 668 EP - 674 VL - 5 IS - 8 SN - 1466-4879, 1466-4879 KW - DNA Primers KW - 0 KW - Recombinant Proteins KW - Eosinophil Cationic Protein KW - EC 3.1.27.- KW - Index Medicus KW - Animals KW - Immunoblotting KW - Liver -- pathology KW - Blotting, Northern KW - Spleen -- metabolism KW - Spleen -- pathology KW - Liver -- metabolism KW - Amino Acid Sequence KW - Mice KW - Sequence Analysis, DNA KW - Selection, Genetic KW - Evolution, Molecular KW - Base Sequence KW - Sequence Alignment KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Schistosoma mansoni KW - Eosinophil Cationic Protein -- metabolism KW - Eosinophil Cationic Protein -- genetics KW - Schistosomiasis mansoni -- pathology KW - Gene Expression KW - Schistosomiasis mansoni -- metabolism KW - Schistosomiasis mansoni -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67141855?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+and+immunity&rft.atitle=Characterization+of+the+divergent+eosinophil+ribonuclease%2C+mEar+6%2C+and+its+expression+in+response+to+Schistosoma+mansoni+infection+in+vivo.&rft.au=Nitto%2C+T%3BDyer%2C+K+D%3BMejia%2C+R+A%3BBystr%C3%B6m%2C+J%3BWynn%2C+T+A%3BRosenberg%2C+H+F&rft.aulast=Nitto&rft.aufirst=T&rft.date=2004-12-01&rft.volume=5&rft.issue=8&rft.spage=668&rft.isbn=&rft.btitle=&rft.title=Genes+and+immunity&rft.issn=14664879&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-18 N1 - Date created - 2004-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - G-CSF-mobilized CD34+ cells cultured in interleukin-2 and stem cell factor generate a phenotypically novel monocyte. AN - 67141216; 15345723 AB - To study the early stages of development from stem cells of the CD56+ cell population [which includes natural killer (NK) cells], granulocyte-colony stimulating factor-mobilized peripheral blood CD34+ cells from healthy donors were sorted to >99% purity and cultured in the presence of stem cell factor and interleukin (IL)-2. After 3 weeks in culture, the majority of cells acquired CD33, with or without human leukocyte antigen-DR and CD14. In 20 stem cell donors tested, 8.7 +/- 8.8% of cells were CD56+. Two major CD56+ subsets were identified: CD56(bright), mainly CD33- cells (7+/-10%, n=11) with large, granular lymphocyte morphology, and CD56dim, mainly CD33+ (2.5+/-2, n=11) cells with macrophage morphology. The CD56bright population had cytoplasmic granzyme A but lacked killer inhibitory receptor, suggesting they were immature NK cells. The CD56dim, CD33+, population lacked NK markers. They may represent a minor subset of normal monocytes at a developmental stage comparable with the rare CD56+ CD33+ hybrid myeloid/NK cell leukemia. Consistent with a monocyte nature, CD56dimCD33+ proliferated and produced a variety of cytokines upon lipopolysaccharide stimulation, including IL-8, IL-6, monocyte chemoattractant protein-1, and macrophage-derived chemokine but not interferon-gamma. In a short-term cytotoxicity assay, they failed to kill but powerfully inhibited the proliferation of the NK-resistant cell line P815. The generation of CD56+ cells was negatively regulated by hyaluronic acid and IL-4, indicating that extracellular matrix may play an important role in the commitment of CD34+ cells into CD56 myeloid and lymphoid lineages. JF - Journal of leukocyte biology AU - Sconocchia, Giuseppe AU - Fujiwara, Hiroshi AU - Rezvani, Katayoun AU - Keyvanfar, Keyvan AU - El Ouriaghli, Frank AU - Grube, Matthias AU - Melenhorst, Jos AU - Hensel, Nancy AU - Barrett, A John AD - Hematopoietic Stem Cell Transplantation Section, National Heart Lung and Blood Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda MD 20892-0001, USA. giuseppe.sconocchia@roswellpark.org Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 1214 EP - 1219 VL - 76 IS - 6 SN - 0741-5400, 0741-5400 KW - Antigens, CD KW - 0 KW - Antigens, CD34 KW - Antigens, CD56 KW - Antigens, Differentiation, Myelomonocytic KW - Biomarkers KW - CD33 protein, human KW - Cytokines KW - Interleukin-2 KW - Sialic Acid Binding Ig-like Lectin 3 KW - Stem Cell Factor KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Hyaluronic Acid KW - 9004-61-9 KW - Granzymes KW - EC 3.4.21.- KW - Serine Endopeptidases KW - GZMA protein, human KW - EC 3.4.21.78 KW - Index Medicus KW - Macrophages -- immunology KW - Extracellular Matrix -- metabolism KW - Cytokines -- biosynthesis KW - Humans KW - Macrophages -- drug effects KW - Lymphocyte Activation -- drug effects KW - Lymphocytes -- immunology KW - Stem Cell Factor -- pharmacology KW - Lymphocytes -- cytology KW - Antigens, Differentiation, Myelomonocytic -- immunology KW - Lymphocytes -- drug effects KW - Cell Proliferation -- drug effects KW - Macrophages -- cytology KW - Interleukin-2 -- pharmacology KW - Granulocyte Colony-Stimulating Factor -- pharmacology KW - Hyaluronic Acid -- metabolism KW - Cell Lineage -- immunology KW - Hyaluronic Acid -- pharmacology KW - Serine Endopeptidases -- metabolism KW - Cells, Cultured KW - Lymphocyte Activation -- immunology KW - Extracellular Matrix -- immunology KW - Cell Lineage -- drug effects KW - Cytotoxicity Tests, Immunologic KW - Immunophenotyping KW - Antigens, CD -- immunology KW - Antigens, CD34 -- immunology KW - Myeloid Progenitor Cells -- immunology KW - Antigens, CD56 -- immunology KW - Killer Cells, Natural -- cytology KW - Killer Cells, Natural -- drug effects KW - Cell Differentiation -- immunology KW - Myeloid Progenitor Cells -- drug effects KW - Monocytes -- cytology KW - Monocytes -- immunology KW - Monocytes -- drug effects KW - Myeloid Progenitor Cells -- cytology KW - Cell Differentiation -- drug effects KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67141216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=G-CSF-mobilized+CD34%2B+cells+cultured+in+interleukin-2+and+stem+cell+factor+generate+a+phenotypically+novel+monocyte.&rft.au=Sconocchia%2C+Giuseppe%3BFujiwara%2C+Hiroshi%3BRezvani%2C+Katayoun%3BKeyvanfar%2C+Keyvan%3BEl+Ouriaghli%2C+Frank%3BGrube%2C+Matthias%3BMelenhorst%2C+Jos%3BHensel%2C+Nancy%3BBarrett%2C+A+John&rft.aulast=Sconocchia&rft.aufirst=Giuseppe&rft.date=2004-12-01&rft.volume=76&rft.issue=6&rft.spage=1214&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 - 2005-01-25 N1 - Date created - 2004-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk. AN - 67139321; 15308583 AB - In the human colon, arachidonic acid is metabolized primarily by cyclooxygenase (COX) and arachidonate lipoxygenase (ALOX) to bioactive lipids, which are implicated in colon cancer risk. Several polymorphisms in ALOX and COX genes have been identified, including G-1752A, G-1699A and Glu254Lys in ALOX5; Gln261Arg in ALOX12; Leu237Met and Val481Ile in COX1; and C-645T and Val511Ala in COX2. Because of the significant role of arachidonic acid metabolism in colon cancer, we hypothesized that these polymorphisms could influence susceptibility to colon cancer. We addressed this hypothesis in African-Americans and Caucasians using colon cancer cases (n = 293) and hospital- (n = 229) and population-based (n = 304) control groups. Polymorphisms did not differ between the control groups (P > 0.05); thus, they are combined for all analyses presented. ALOX5 Glu254Lys and COX2 C-645T and Val511Ala allele frequencies differed between Caucasians and African-American controls (P < 0.001). The ALOX5 -1752 and -1699 polymorphisms were in linkage disequilibrium (P < 0.001) and associated with a decreased risk in Caucasians in ALOX5 haplotype analyses (P = 0.03). Furthermore, an inverse association was observed between A alleles at positions -1752 and -1699 of ALOX5 and colon cancer risk in Caucasians, but not in African-Americans. Caucasians with A alleles at ALOX5 -1752 had a reduced odds of colon cancer versus those with G alleles [odds ratio (OR) (GA versus GG), 0.63; 95% confidence interval (CI), 0.39-1.01; OR (AA versus GG), 0.33; 95% CI, 0.07-1.65, P(trend) = 0.02]. Similar results were observed for ALOX5 G-1699A [OR (GA versus GG), 0.59, 95% CI, 0.37-0.94; OR (AA versus GG), 0.27, 95% CI, 0.06-1.32, P(trend) = 0.01]. Statistically significant associations with colon cancer were not observed for the other polymorphisms investigated. We have shown for the first time that a haplotype containing ALOX5 G-1752A and G-1699A in a negative regulatory region of the promoter may influence colon cancer risk in Caucasians. JF - Carcinogenesis AU - Goodman, Julie E AU - Bowman, Elise D AU - Chanock, Stephen J AU - Alberg, Anthony J AU - Harris, Curtis C AD - Laboratory of Human Carcinogensis, Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 2467 EP - 2472 VL - 25 IS - 12 SN - 0143-3334, 0143-3334 KW - Isoenzymes KW - 0 KW - Membrane Proteins KW - Arachidonate Lipoxygenases KW - EC 1.13.11.- KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - PTGS1 protein, human KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Humans KW - African Americans KW - Aged KW - Linkage Disequilibrium KW - Haplotypes -- genetics KW - Risk Factors KW - European Continental Ancestry Group KW - Case-Control Studies KW - Middle Aged KW - Genetic Predisposition to Disease KW - Female KW - Male KW - Colonic Neoplasms -- epidemiology KW - Colonic Neoplasms -- genetics KW - Polymorphism, Genetic -- genetics KW - Arachidonate Lipoxygenases -- genetics KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Isoenzymes -- genetics KW - Colonic Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67139321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Arachidonate+lipoxygenase+%28ALOX%29+and+cyclooxygenase+%28COX%29+polymorphisms+and+colon+cancer+risk.&rft.au=Goodman%2C+Julie+E%3BBowman%2C+Elise+D%3BChanock%2C+Stephen+J%3BAlberg%2C+Anthony+J%3BHarris%2C+Curtis+C&rft.aulast=Goodman&rft.aufirst=Julie&rft.date=2004-12-01&rft.volume=25&rft.issue=12&rft.spage=2467&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-13 N1 - Date created - 2004-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicogenomics and systems toxicology: aims and prospects. AN - 67134915; 15573125 AB - Toxicogenomics combines transcript, protein and metabolite profiling with conventional toxicology to investigate the interaction between genes and environmental stress in disease causation. The patterns of altered molecular expression that are caused by specific exposures or disease outcomes have revealed how several toxicants act and cause disease. Despite these success stories, the field faces noteworthy challenges in discriminating the molecular basis of toxicity. We argue that toxicology is gradually evolving into a systems toxicology that will eventually allow us to describe all the toxicological interactions that occur within a living system under stress and use our knowledge of toxicogenomic responses in one species to predict the modes-of-action of similar agents in other species. JF - Nature reviews. Genetics AU - Waters, Michael D AU - Fostel, Jennifer M AD - National Center for Toxicogenomics, National Institute of Environmental Health Sciences, PO Box 12233, MD F1-05, 111 Alexander Drive, Research Triangle Park, North Carolina 27709-2233, USA. waters2@niehs.nih.gov Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 936 EP - 948 VL - 5 IS - 12 SN - 1471-0056, 1471-0056 KW - Index Medicus KW - Ecology KW - Gene Expression Profiling KW - Animals KW - Humans KW - Proteomics KW - Databases, Factual KW - Forecasting KW - Genetic Predisposition to Disease KW - Computational Biology KW - Systems Theory KW - Toxicogenetics KW - Toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67134915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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.+Genetics&rft.atitle=Toxicogenomics+and+systems+toxicology%3A+aims+and+prospects.&rft.au=Waters%2C+Michael+D%3BFostel%2C+Jennifer+M&rft.aulast=Waters&rft.aufirst=Michael&rft.date=2004-12-01&rft.volume=5&rft.issue=12&rft.spage=936&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Genetics&rft.issn=14710056&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-17 N1 - Date created - 2004-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of energy balance on cancer in genetically altered mice. AN - 67126709; 15570044 AB - Evidence has accumulated from laboratory-based animal experiments and population-based human epidemiological studies that lifestyle factors that affect energy balance, such as caloric intake, nutritional status, and exercise, act in concert with genetic susceptibility to influence cancer development and progression. The use of animal models with specific genetic alterations, in combination with lifestyle modifications that alter overall energy balance, has contributed to a greater understanding of the mechanistic changes occurring during carcinogenesis and to the identification of points of intervention. Studies in our laboratory focusing on the role of energy balance and genetic susceptibility in mice deficient in one (+/-) or both (-/-) alleles of the p53 tumor suppressor gene and mice with a mutant APC allele (APC(Min)) showed that calorie restriction decreases tumor burden, increases tumor latency, and decreases serum insulin-like growth factor (IGF)-1 and leptin levels. Data from our studies, combined with results from other animal and human studies, have established a role for IGF-1 in carcinogenesis. Studies using genetic models of cancer that have been interbred with mice with abnormal levels of IGF-1 will enable the examination of combined effects of energy balance and genetic alterations on the cancer process. Models that integrate lifestyle and genetic effects in a single system provide a physiologically intact system in which combination interventions and therapies for cancer prevention can be tested and validated, thus building a strong preclinical foundation that will inform the development of clinical trials and add perspective to epidemiological studies. JF - The Journal of nutrition AU - Patel, Arti C AU - Nunez, Nomeli P AU - Perkins, Susan N AU - Barrett, J Carl AU - Hursting, Stephen D AD - Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 3394S EP - 3398S VL - 134 IS - 12 Suppl SN - 0022-3166, 0022-3166 KW - Tumor Suppressor Protein p53 KW - 0 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - Animals KW - Insulin-Like Growth Factor I -- physiology KW - Humans KW - Energy Intake KW - Insulin-Like Growth Factor I -- analysis KW - Mice KW - Mice, Transgenic KW - Mice, Knockout KW - Genes, APC KW - Life Style KW - Alleles KW - Heterozygote KW - Genes, p53 -- genetics KW - Mutation KW - Female KW - Male KW - Tumor Suppressor Protein p53 -- deficiency KW - Neoplasms -- prevention & control KW - Genetic Predisposition to Disease KW - Neoplasms -- therapy KW - Energy Metabolism KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67126709?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Effects+of+energy+balance+on+cancer+in+genetically+altered+mice.&rft.au=Patel%2C+Arti+C%3BNunez%2C+Nomeli+P%3BPerkins%2C+Susan+N%3BBarrett%2C+J+Carl%3BHursting%2C+Stephen+D&rft.aulast=Patel&rft.aufirst=Arti&rft.date=2004-12-01&rft.volume=134&rft.issue=12+Suppl&rft.spage=3394S&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 - 2005-01-13 N1 - Date created - 2004-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Doxorubicin inhibits DNMT1, resulting in conditional apoptosis. AN - 67107835; 15340041 AB - Chemotherapy using DNA intercalators is one of the most successful approaches to cancer treatment. Although DNA intercalators are believed to inhibit DNA polymerases and topoisomerases, resulting in the induction of apoptosis in tumor cells, other factors potentially inhibited by the anthracycline antibiotics remain to be elucidated. Herein, we show that the enzymatic activity of DNMT1, the primary DNA methyltransferase in mammalian cells, is inhibited by DNA intercalators, such as doxorubicin, in an in vitro assay. Enzymatic analyses indicate that doxorubicin inhibits the catalytic activity of DNMT1 via DNA intercalation. We also found that apoptosis was induced in DNMT1(+/+) HCT116 cells by only a limited range of doxorubicin dose, meaning that apoptotic cell death is "conditional" with respect to the concentration of the DNA intercalating drug. It is noteworthy that conditional apoptosis is not observed in human colorectal cancer cells lacking DNMT1 but can be induced in DNMT1(-/-) cells by transfection of a plasmid expressing DNMT1. Our results suggest that DNMT1 is one of the major targets of doxorubicin resulting in drug-induced apoptosis in human cancer cells. We propose that expression levels of DNMT1 in tumor cells may affect the effectiveness of doxorubicin in chemotherapy. JF - Molecular pharmacology AU - Yokochi, Tomoki AU - Robertson, Keith D AD - Epigenetic Gene Regulation and Cancer Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 1415 EP - 1420 VL - 66 IS - 6 SN - 0026-895X, 0026-895X KW - Intercalating Agents KW - 0 KW - Recombinant Proteins KW - S-Adenosylmethionine KW - 7LP2MPO46S KW - Doxorubicin KW - 80168379AG KW - DNA (Cytosine-5-)-Methyltransferase KW - EC 2.1.1.37 KW - DNA (cytosine-5-)-methyltransferase 1 KW - Index Medicus KW - Intercalating Agents -- pharmacology KW - Cell Survival -- drug effects KW - Dose-Response Relationship, Drug KW - Kinetics KW - Humans KW - S-Adenosylmethionine -- pharmacology KW - Cell Line, Tumor KW - Recombinant Proteins -- antagonists & inhibitors KW - Colorectal Neoplasms KW - DNA (Cytosine-5-)-Methyltransferase -- genetics KW - DNA (Cytosine-5-)-Methyltransferase -- antagonists & inhibitors KW - Apoptosis -- drug effects KW - Doxorubicin -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67107835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Doxorubicin+inhibits+DNMT1%2C+resulting+in+conditional+apoptosis.&rft.au=Yokochi%2C+Tomoki%3BRobertson%2C+Keith+D&rft.aulast=Yokochi&rft.aufirst=Tomoki&rft.date=2004-12-01&rft.volume=66&rft.issue=6&rft.spage=1415&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 - 2005-03-24 N1 - Date created - 2004-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Application of comparative functional genomics to identify best-fit mouse models to study human cancer. AN - 67107708; 15565109 AB - Genetically modified mice have been extensively used for analyzing the molecular events that occur during tumor development. In many, if not all, cases, however, it is uncertain to what extent the mouse models reproduce features observed in the corresponding human conditions. This is due largely to lack of precise methods for direct and comprehensive comparison at the molecular level of the mouse and human tumors. Here we use global gene expression patterns of 68 hepatocellular carcinomas (HCCs) from seven different mouse models and 91 human HCCs from predefined subclasses to obtain direct comparison of the molecular features of mouse and human HCCs. Gene expression patterns in HCCs from Myc, E2f1 and Myc E2f1 transgenic mice were most similar to those of the better survival group of human HCCs, whereas the expression patterns in HCCs from Myc Tgfa transgenic mice and in diethylnitrosamine-induced mouse HCCs were most similar to those of the poorer survival group of human HCCs. Gene expression patterns in HCCs from Acox1(-/-) mice and in ciprofibrate-induced HCCs were least similar to those observed in human HCCs. We conclude that our approach can effectively identify appropriate mouse models to study human cancers. JF - Nature genetics AU - Lee, Ju-Seog AU - Chu, In-Sun AU - Mikaelyan, Arsen AU - Calvisi, Diego F AU - Heo, Jeonghoon AU - Reddy, Janardan K AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4262, USA. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 1306 EP - 1311 VL - 36 IS - 12 SN - 1061-4036, 1061-4036 KW - Index Medicus KW - Animals KW - Apoptosis -- genetics KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Mice, Transgenic KW - Immunohistochemistry KW - Cluster Analysis KW - Gene Expression Profiling KW - Genomics -- methods KW - Carcinoma, Hepatocellular -- genetics KW - Disease Models, Animal KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67107708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Application+of+comparative+functional+genomics+to+identify+best-fit+mouse+models+to+study+human+cancer.&rft.au=Lee%2C+Ju-Seog%3BChu%2C+In-Sun%3BMikaelyan%2C+Arsen%3BCalvisi%2C+Diego+F%3BHeo%2C+Jeonghoon%3BReddy%2C+Janardan+K%3BThorgeirsson%2C+Snorri+S&rft.aulast=Lee&rft.aufirst=Ju-Seog&rft.date=2004-12-01&rft.volume=36&rft.issue=12&rft.spage=1306&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 - 2005-02-04 N1 - Date created - 2004-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ENU induced mutations causing congenital cardiovascular anomalies. AN - 67107370; 15548583 AB - We used non-invasive high frequency ultrasound to screen N-ethyl-N-nitrosourea mutagenized mouse fetuses for congenital cardiovascular anomalies. We ultrasound scanned 7546 mouse fetuses from 262 mutagenized families, and identified 124 families with cardiovascular defects. Represented were most of the major congenital cardiovascular anomalies seen clinically. The ENU-induced mutations in several families were mapped using polymorphic microsatellite DNA markers. One family with forelimb anomalies and ventricular septal defects, phenotypes similar to Holt-Oram syndrome, and one family with transposition of the great arteries and heart situs anomalies were mapped to different regions of mouse chromosome 4. A third mutation causing persistent truncus arteriosus and craniofacial defects, phenotypes reminiscent of DiGeorge syndrome, was mapped to mouse chromosome 2. We note that mouse chromosomes 4 and 2 do not contain Tbx5 or Tbx1, genes previously linked to Holt-Oram and DiGeorge syndromes, respectively. In two other families, the ENU-induced mutation was identified--Sema3CL605P was associated with persistent truncus arteriosus with interrupted aortic arch, and the Gja1W45X connexin43 mutation caused conotruncal malformation and coronary aneurysms. Although our screen was designed as a recessive screen, a number of the mutations showed cardiovascular phenotypes in both heterozygote and homozygote animals. These studies show the efficacy of ENU mutagenesis and high-throughput ultrasound phenotyping in recovering mutations causing a wide spectrum of congenital heart defects. These ENU-induced mutations hold promise in yielding new insights into the genetic basis for human congenital heart disease. JF - Development (Cambridge, England) AU - Yu, Qing AU - Shen, Yuan AU - Chatterjee, Bishwanath AU - Siegfried, Brett H AU - Leatherbury, Linda AU - Rosenthal, Julie AU - Lucas, John F AU - Wessels, Andy AU - Spurney, Chris F AU - Wu, Ying-Jie AU - Kirby, Margaret L AU - Svenson, Karen AU - Lo, Cecilia W AD - Laboratory of Developmental Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-8019, USA. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 6211 EP - 6223 VL - 131 IS - 24 SN - 0950-1991, 0950-1991 KW - Connexin 43 KW - 0 KW - T-Box Domain Proteins KW - T-box transcription factor 5 KW - Tbx1 protein, mouse KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Animals KW - Amino Acid Sequence KW - Mice KW - Truncus Arteriosus, Persistent -- diagnostic imaging KW - Ultrasonography KW - Limb Deformities, Congenital -- diagnostic imaging KW - Connexin 43 -- genetics KW - Truncus Arteriosus, Persistent -- genetics KW - Chromosomes, Mammalian -- genetics KW - T-Box Domain Proteins -- genetics KW - Molecular Sequence Data KW - Female KW - Limb Deformities, Congenital -- genetics KW - Mutation -- drug effects KW - DiGeorge Syndrome -- diagnostic imaging KW - Heart Defects, Congenital -- diagnostic imaging KW - Ethylnitrosourea -- toxicity KW - DiGeorge Syndrome -- genetics KW - Fetus -- abnormalities KW - Heart Defects, Congenital -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67107370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=ENU+induced+mutations+causing+congenital+cardiovascular+anomalies.&rft.au=Yu%2C+Qing%3BShen%2C+Yuan%3BChatterjee%2C+Bishwanath%3BSiegfried%2C+Brett+H%3BLeatherbury%2C+Linda%3BRosenthal%2C+Julie%3BLucas%2C+John+F%3BWessels%2C+Andy%3BSpurney%2C+Chris+F%3BWu%2C+Ying-Jie%3BKirby%2C+Margaret+L%3BSvenson%2C+Karen%3BLo%2C+Cecilia+W&rft.aulast=Yu&rft.aufirst=Qing&rft.date=2004-12-01&rft.volume=131&rft.issue=24&rft.spage=6211&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-18 N1 - Date created - 2004-11-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene expression profiling identifies a unique androgen-mediated inflammatory/immune signature and a PTEN (phosphatase and tensin homolog deleted on chromosome 10)-mediated apoptotic response specific to the rat ventral prostate. AN - 67106091; 15358834 AB - Understanding androgen regulation of gene expression is critical for deciphering mechanisms responsible for the transition from androgen-responsive (AR) to androgen-independent (AI) prostate cancer (PCa). To identify genes differentially regulated by androgens in each prostate lobe, the rat castration model was used. Microarray analysis was performed to compare dorsolateral (DLP) and ventral prostate (VP) samples from sham-castrated, castrated, and testosterone-replenished castrated rats. Our data demonstrate that, after castration, the VP and the DLP differed in the number of genes with altered expression (1496 in VP vs. 256 in DLP) and the nature of pathways modulated. Gene signatures related to apoptosis and immune response specific to the ventral prostate were identified. Microarray and RT-PCR analyses demonstrated the androgen repression of IGF binding protein-3 and -5, CCAAT-enhancer binding protein-delta, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) genes, previously implicated in apoptosis. We show that PTEN protein was increased only in the luminal epithelial cells of the VP, suggesting that it may be a key mediator of VP apoptosis in the absence of androgens. The castration-induced immune/inflammatory gene cluster observed specifically in the VP included IL-15 and IL-18. Immunostaining of the VP, but not the DLP, showed an influx of T cells, macrophages, and mast cells, suggesting that these cells may be the source of the immune signature genes. Interestingly, IL-18 was localized mainly to the basal epithelial cells and the infiltrating macrophages in the regressing VP, whereas IL-15 was induced in the luminal epithelium. The VP castration model exhibits immune cell infiltration and loss of PTEN that is often observed in progressive PCa, thereby making this model useful for further delineation of androgen-regulated gene expression with relevance to PCa. JF - Molecular endocrinology (Baltimore, Md.) AU - Desai, Kartiki V AU - Michalowska, Aleksandra M AU - Kondaiah, Paturu AU - Ward, Jerrold M AU - Shih, Joanna H AU - Green, Jeffrey E AD - Laboratory of Cell Regulation and Carcinogenesis, 41 Medlar's Drive, Room C619, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 2895 EP - 2907 VL - 18 IS - 12 SN - 0888-8809, 0888-8809 KW - Androgens KW - 0 KW - CCAAT-Enhancer-Binding Proteins KW - Cebpd protein, rat KW - Insulin-Like Growth Factor Binding Protein 3 KW - Interleukin-15 KW - Interleukin-18 KW - Interleukins KW - RNA, Messenger KW - Transcription Factors KW - Tumor Suppressor Proteins KW - CCAAT-Enhancer-Binding Protein-delta KW - 142662-43-9 KW - Testosterone KW - 3XMK78S47O KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - PTEN Phosphohydrolase KW - EC 3.1.3.67 KW - Index Medicus KW - Animals KW - Oligonucleotide Array Sequence Analysis KW - Immune System -- cytology KW - Interleukin-15 -- genetics KW - Disease Models, Animal KW - Testosterone -- physiology KW - Castration KW - Rats KW - Down-Regulation KW - Neoplasms, Hormone-Dependent -- immunology KW - CCAAT-Enhancer-Binding Proteins -- genetics KW - Interleukin-18 -- genetics KW - Male KW - Insulin-Like Growth Factor Binding Protein 3 -- analysis KW - Insulin-Like Growth Factor Binding Protein 3 -- genetics KW - Prostatic Neoplasms -- immunology KW - RNA, Messenger -- analysis KW - Prostatic Neoplasms -- genetics KW - Transcription Factors -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Gene Expression Profiling KW - Testosterone -- pharmacology KW - RNA, Messenger -- metabolism KW - Neoplasms, Hormone-Dependent -- genetics KW - Gene Expression Regulation, Neoplastic -- genetics KW - Prostate -- immunology KW - Apoptosis KW - Tumor Suppressor Proteins -- analysis KW - Androgens -- physiology KW - Tumor Suppressor Proteins -- genetics KW - Prostate -- metabolism KW - Phosphoric Monoester Hydrolases -- genetics KW - Phosphoric Monoester Hydrolases -- analysis KW - Androgens -- pharmacology KW - Interleukins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67106091?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Gene+expression+profiling+identifies+a+unique+androgen-mediated+inflammatory%2Fimmune+signature+and+a+PTEN+%28phosphatase+and+tensin+homolog+deleted+on+chromosome+10%29-mediated+apoptotic+response+specific+to+the+rat+ventral+prostate.&rft.au=Desai%2C+Kartiki+V%3BMichalowska%2C+Aleksandra+M%3BKondaiah%2C+Paturu%3BWard%2C+Jerrold+M%3BShih%2C+Joanna+H%3BGreen%2C+Jeffrey+E&rft.aulast=Desai&rft.aufirst=Kartiki&rft.date=2004-12-01&rft.volume=18&rft.issue=12&rft.spage=2895&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 - 2005-03-25 N1 - Date created - 2004-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of ATP-binding cassette transporter expression in drug-selected cell lines by a microarray dedicated to multidrug resistance. AN - 67105316; 15342794 AB - Discovery of the multidrug resistance protein 1 (MDR1), an ATP-binding cassette (ABC) transporter able to transport many anticancer drugs, was a clinically relevant breakthrough in multidrug resistance research. Although the overexpression of ABC transporters such as P-glycoprotein/ABCB1, MRP1/ABCC1, and MXR/ABCG2 seems to be a major cause of failure in the treatment of cancer, acquired resistance to multiple anticancer drugs may also be multifactorial, involving alteration of detoxification processes, apoptosis, DNA repair, drug uptake, and overexpression of other ABC transporters. As a tool for the study of such phenomena, we designed and created a microarray platform, the ABC-ToxChip, to evaluate relative levels of transcriptional activation among genes involved in the various mechanisms of resistance. In the ABC-ToxChip, a comprehensive set of genes important in toxicological responses (represented by 2200 cDNA probes) is complemented with probes specifically matching ABC transporters as well as oligonucleotides representing 18,000 unique human genes. By comparing the transcriptional profiles of KB-3-1 and DU-145 parental cells with resistant derivatives selected in colchicine (KB-8-5), and 9-nitro-camptothecin (RCO.1), respectively, we demonstrate that ABC transporters (ABCB1/MDR1 and ABCC2/MRP2, respectively) show dramatic overexpression, whereas the glutathione S-transferase gene GST-Pi shows the strongest decrease in expression among the 20,000 genes studied. The results were confirmed by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. The custom-designed ABC-Tox microarray presented here will be helpful to elucidate mechanisms leading to anticancer drug resistance. JF - Molecular pharmacology AU - Annereau, Jean-Philippe AU - Szakács, Gergely AU - Tucker, Charles J AU - Arciello, Angela AU - Cardarelli, Carol AU - Collins, Jennifer AU - Grissom, Sherry AU - Zeeberg, Barry R AU - Reinhold, William AU - Weinstein, John N AU - Pommier, Yves AU - Paules, Richard S AU - Gottesman, Michael M AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4256, USA. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 1397 EP - 1405 VL - 66 IS - 6 SN - 0026-895X, 0026-895X KW - DNA Probes KW - 0 KW - Index Medicus KW - DNA Repair KW - Apoptosis KW - Exons KW - Humans KW - Biological Transport KW - Cell Line KW - Oligonucleotide Array Sequence Analysis KW - ATP-Binding Cassette Transporters -- metabolism KW - ATP-Binding Cassette Transporters -- genetics KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67105316?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analysis+of+ATP-binding+cassette+transporter+expression+in+drug-selected+cell+lines+by+a+microarray+dedicated+to+multidrug+resistance.&rft.au=Annereau%2C+Jean-Philippe%3BSzak%C3%A1cs%2C+Gergely%3BTucker%2C+Charles+J%3BArciello%2C+Angela%3BCardarelli%2C+Carol%3BCollins%2C+Jennifer%3BGrissom%2C+Sherry%3BZeeberg%2C+Barry+R%3BReinhold%2C+William%3BWeinstein%2C+John+N%3BPommier%2C+Yves%3BPaules%2C+Richard+S%3BGottesman%2C+Michael+M&rft.aulast=Annereau&rft.aufirst=Jean-Philippe&rft.date=2004-12-01&rft.volume=66&rft.issue=6&rft.spage=1397&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 - 2005-03-24 N1 - Date created - 2004-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective nonsteroidal anti-inflammatory drugs induce thymosin beta-4 and alter actin cytoskeletal organization in human colorectal cancer cells. AN - 67095404; 15292456 AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory effects and have been shown to have chemopreventive effects as well. NSAIDs inhibit cyclooxygenase (COX) activity to exert their anti-inflammatory effects, but it is not clear whether their antitumorigenic ability is through COX inhibition. Using subtractive hybridization, we previously identified a novel member of the transforming growth factor-beta superfamily that has antitumorigenic activity from indomethacin-treated HCT-116 human colorectal cancer cells. On further investigation of this library, we now report the identification of a new cDNA corresponding to the thymosin beta-4 gene. Thymosin beta-4 is a small peptide that is known for its actin-sequestering function, and it is associated with the induction of angiogenesis, accelerated wound healing, and metastatic potential of tumor cells. However, only selective NSAIDs induce thymosin beta-4 expression in a time- and concentration-dependent manner. For example, indomethacin and SC-560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole] induce thymosin beta-4 expression whereas sulindac sulfide does not. We show that selective NSAIDs induce actin cytoskeletal reorganization, a precursory step to many dynamic processes regulating growth and motility including tumorigenesis. This is the first report to link thymosin beta-4 induction with NSAIDs. These data suggest that NSAIDs alter the expression of a diverse number of genes and provide new insights into the chemopreventive and biological activity of these drugs. JF - The Journal of pharmacology and experimental therapeutics AU - Jain, Anshu K AU - Moore, Scott M AU - Yamaguchi, Kiyoshi AU - Eling, Thomas E AU - Baek, Seung Joon AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 885 EP - 891 VL - 311 IS - 3 SN - 0022-3565, 0022-3565 KW - Actins KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - Cytokines KW - GDF15 protein, human KW - Growth Differentiation Factor 15 KW - Indicators and Reagents KW - Pyrazoles KW - RNA, Neoplasm KW - SC 560 KW - thymosin beta(4) KW - 549LM7U24W KW - Thymosin KW - 61512-21-8 KW - Prostaglandin-Endoperoxide Synthases KW - EC 1.14.99.1 KW - Dinoprostone KW - K7Q1JQR04M KW - Indomethacin KW - XXE1CET956 KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Cytokines -- genetics KW - Dinoprostone -- pharmacology KW - Blotting, Northern KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Line, Tumor KW - Chromatography, High Pressure Liquid KW - Indomethacin -- pharmacology KW - Pyrazoles -- pharmacology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Fluorescent Antibody Technique KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Cytoskeleton -- metabolism KW - Colorectal Neoplasms -- metabolism KW - Actins -- metabolism KW - Thymosin -- genetics KW - Thymosin -- biosynthesis KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67095404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Selective+nonsteroidal+anti-inflammatory+drugs+induce+thymosin+beta-4+and+alter+actin+cytoskeletal+organization+in+human+colorectal+cancer+cells.&rft.au=Jain%2C+Anshu+K%3BMoore%2C+Scott+M%3BYamaguchi%2C+Kiyoshi%3BEling%2C+Thomas+E%3BBaek%2C+Seung+Joon&rft.aulast=Jain&rft.aufirst=Anshu&rft.date=2004-12-01&rft.volume=311&rft.issue=3&rft.spage=885&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 - 2005-01-13 N1 - Date created - 2004-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug addiction: the neurobiology of behaviour gone awry. AN - 67089597; 15550951 AB - Drug addiction manifests as a compulsive drive to take a drug despite serious adverse consequences. This aberrant behaviour has traditionally been viewed as bad "choices" that are made voluntarily by the addict. However, recent studies have shown that repeated drug use leads to long-lasting changes in the brain that undermine voluntary control. This, combined with new knowledge of how environmental, genetic and developmental factors contribute to addiction, should bring about changes in our approach to the prevention and treatment of addiction. JF - Nature reviews. Neuroscience AU - Volkow, Nora D AU - Li, Ting-Kai AD - National Institute on Drug Abuse/NIH, Bethesda, MD 20892, USA. nvolkow@nida.nih.gov Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 963 EP - 970 VL - 5 IS - 12 SN - 1471-003X, 1471-003X KW - Index Medicus KW - Animals KW - Humans KW - Brain -- metabolism KW - Behavior, Addictive -- psychology KW - Behavior, Addictive -- metabolism KW - Substance-Related Disorders -- metabolism KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67089597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+reviews.+Neuroscience&rft.atitle=Drug+addiction%3A+the+neurobiology+of+behaviour+gone+awry.&rft.au=Volkow%2C+Nora+D%3BLi%2C+Ting-Kai&rft.aulast=Volkow&rft.aufirst=Nora&rft.date=2004-12-01&rft.volume=5&rft.issue=12&rft.spage=963&rft.isbn=&rft.btitle=&rft.title=Nature+reviews.+Neuroscience&rft.issn=1471003X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-06 N1 - Date created - 2004-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of highly active antiretroviral therapy (HAART) on pharmacokinetics and pharmacodynamics of doxorubicin in patients with HIV-associated non-Hodgkin's lymphoma. AN - 67085071; 15550586 AB - We demonstrated that highly active antiretroviral therapy (HAART) increases the toxic effect of cyclophosphamide, vincristine, doxorubicin (DOX) and prednisone (CHOP) in HIV-patients with non-Hodgkin's lymphoma (NHL). To ascertain the cause of increased toxicity, we investigated the pharmacokinetics of DOX in HIV-patients with NHL treated with CHOP with and without HAART. Complete pharmacokinetics and pharmacodynamic analysis was determined in 19 patients during 38 cycles of chemotherapy: 19 cycles with CHOP and 19 CHOP + HAART in a crossover-designed study. HAART included protease inhibitors indinavir (IDV) in nine patients, saquinavir (SQV) hard gel in six patients and nelfinavir (NFV) in four patients. No significant effects of HAART on pharmacokinetics parameters of DOX were observed. Similarly, no differential effect on DOX pharmacokinetics among IDV, SQV, and NFV was evidenced. Significant associations (P=0.012) were observed between DOX AUC0-infinity (area under the concentration curve) and G3-G4 WHO haematologic toxicity, in patients treated with CHOP alone, but not in those treated with CHOP + HAART (P = not significant). We demonstrated that HAART therapy has no significant effect on DOX pharmacokinetics. DOX AUC appears to be a predictor of toxicity only in patients treated with CHOP alone. Other factors beside DOX plasma levels are detrimental for toxicity after CHOP + HAART. Therefore, pharmacodynamic interactions between HAART and DOX should be considered. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Toffoli, G AU - Corona, G AU - Cattarossi, G AU - Boiocchi, M AU - Di Gennaro, G AU - Tirelli, U AU - Vaccher, E AD - Experimental and Clinical Pharamcology Unit, National Cancer Institute, Aviano, Italy. gtoffoli@cro.it Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 1805 EP - 1809 VL - 15 IS - 12 SN - 0923-7534, 0923-7534 KW - Antibiotics, Antineoplastic KW - 0 KW - Vincristine KW - 5J49Q6B70F KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Drug Interactions KW - Area Under Curve KW - Humans KW - Adult KW - Vincristine -- administration & dosage KW - Cross-Over Studies KW - Middle Aged KW - Prednisone -- administration & dosage KW - Male KW - Female KW - Doxorubicin -- pharmacokinetics KW - Doxorubicin -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- administration & dosage KW - Doxorubicin -- administration & dosage KW - Lymphoma, AIDS-Related -- virology KW - Antibiotics, Antineoplastic -- pharmacokinetics KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Doxorubicin -- pharmacology KW - HIV Infections -- complications KW - Antibiotics, Antineoplastic -- pharmacology KW - HIV Infections -- drug therapy KW - Antiretroviral Therapy, Highly Active KW - Lymphoma, AIDS-Related -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Lymphoma, Non-Hodgkin -- virology KW - Antibiotics, Antineoplastic -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67085071?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Topics+in+Language+Disorders&rft.atitle=Reading%2C+Writing%2C+and+Spoken+Language+Assessment+Profiles+for+Students+Who+Are+Deaf+and+Hard+of+Hearing+Compared+with+Students+with+Language+Learning+Disabilities&rft.au=Nelson%2C+Nickola+Wolf%3BCrumpton%2C+Teresa&rft.aulast=Nelson&rft.aufirst=Nickola&rft.date=2015-01-01&rft.volume=35&rft.issue=2&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Topics+in+Language+Disorders&rft.issn=02718294&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-28 N1 - Date created - 2004-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Models for evaluating agents intended for the prophylaxis, mitigation and treatment of radiation injuries. Report of an NCI Workshop, December 3-4, 2003. AN - 67085021; 15548121 AB - To develop approaches to prophylaxis/protection, mitigation and treatment of radiation injuries, appropriate models are needed that integrate the complex events that occur in the radiation-exposed organism. While the spectrum of agents in clinical use or preclinical development is limited, new research findings promise improvements in survival after whole-body irradiation and reductions in the risk of adverse effects of radiotherapy. Approaches include agents that act on the initial radiochemical events, agents that prevent or reduce progression of radiation damage, and agents that facilitate recovery from radiation injuries. While the mechanisms of action for most of the agents with known efficacy are yet to be fully determined, many seem to be operating at the tissue, organ or whole animal level as well as the cellular level. Thus research on prophylaxis/protection, mitigation and treatment of radiation injuries will require studies in whole animal models. Discovery, development and delivery of effective radiation modulators will also require collaboration among researchers in diverse fields such as radiation biology, inflammation, physiology, toxicology, immunology, tissue injury, drug development and radiation oncology. Additional investment in training more scientists in radiation biology and in the research portfolio addressing radiological and nuclear terrorism would benefit the general population in case of a radiological terrorism event or a large-scale accidental event as well as benefit patients treated with radiation. JF - Radiation research AU - Stone, Helen B AU - Moulder, John E AU - Coleman, C Norman AU - Ang, K Kian AU - Anscher, Mitchell S AU - Barcellos-Hoff, Mary Helen AU - Dynan, William S AU - Fike, John R AU - Grdina, David J AU - Greenberger, Joel S AU - Hauer-Jensen, Martin AU - Hill, Richard P AU - Kolesnick, Richard N AU - Macvittie, Thomas J AU - Marks, Cheryl AU - McBride, William H AU - Metting, Noelle AU - Pellmar, Terry AU - Purucker, Mary AU - Robbins, Mike E AU - Schiestl, Robert H AU - Seed, Thomas M AU - Tomaszewski, Joseph E AU - Travis, Elizabeth L AU - Wallner, Paul E AU - Wolpert, Mary AU - Zaharevitz, Daniel AD - National Cancer Institute, Bethesda, Maryland 20892, USA. stoneh@mail.nih.gov Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 711 EP - 728 VL - 162 IS - 6 SN - 0033-7587, 0033-7587 KW - Index Medicus KW - Space life sciences KW - Kidney -- radiation effects KW - Animals KW - Gastrointestinal Tract -- radiation effects KW - Skin -- radiation effects KW - Central Nervous System -- radiation effects KW - Humans KW - Zebrafish KW - Lung -- radiation effects KW - Hematopoietic System -- radiation effects KW - Radiation Injuries -- drug therapy KW - Radiation Injuries -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67085021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Models+for+evaluating+agents+intended+for+the+prophylaxis%2C+mitigation+and+treatment+of+radiation+injuries.+Report+of+an+NCI+Workshop%2C+December+3-4%2C+2003.&rft.au=Stone%2C+Helen+B%3BMoulder%2C+John+E%3BColeman%2C+C+Norman%3BAng%2C+K+Kian%3BAnscher%2C+Mitchell+S%3BBarcellos-Hoff%2C+Mary+Helen%3BDynan%2C+William+S%3BFike%2C+John+R%3BGrdina%2C+David+J%3BGreenberger%2C+Joel+S%3BHauer-Jensen%2C+Martin%3BHill%2C+Richard+P%3BKolesnick%2C+Richard+N%3BMacvittie%2C+Thomas+J%3BMarks%2C+Cheryl%3BMcBride%2C+William+H%3BMetting%2C+Noelle%3BPellmar%2C+Terry%3BPurucker%2C+Mary%3BRobbins%2C+Mike+E%3BSchiestl%2C+Robert+H%3BSeed%2C+Thomas+M%3BTomaszewski%2C+Joseph+E%3BTravis%2C+Elizabeth+L%3BWallner%2C+Paul+E%3BWolpert%2C+Mary%3BZaharevitz%2C+Daniel&rft.aulast=Stone&rft.aufirst=Helen&rft.date=2004-12-01&rft.volume=162&rft.issue=6&rft.spage=711&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 - 2004-12-30 N1 - Date created - 2004-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analgesic effect of sustained-release flurbiprofen administered at the site of tissue injury in the oral surgery model. AN - 67072657; 15545314 AB - Nonsteroidal anti-inflammatory drugs produce their analgesic and adverse effects through interaction with cyclooxygenase in a variety of tissues. The authors evaluated the therapeutic potential of administering a sustained-release formulation of flurbiprofen into a surgical wound following oral surgery to produce analgesia at the site of injury while minimizing exposure to potential targets for toxicity. Subjects (N = 98) received 1 of 8 treatments: flurbiprofen in a microparticle formulation in doses of 3.125 mg, 6.25 mg, 12.5 mg, 25 mg, or 50 mg; PO flurbiprofen 25 mg or 50 mg; or placebo. The flurbiprofen microparticle formulation or matching placebo was placed into the extraction sites at the end of surgery (removal of 2 lower impacted third molars). The sum of the pain visual analog scale over the 6-hour observation period demonstrated significantly less pain (P < .05) for flurbiprofen microparticle in comparison with placebo. Fewer subjects remedicated in the flurbiprofen microparticle drug groups, primarily for the 12.5-mg and higher doses. The incidence of adverse effects and local complications did not differ across groups. These data suggest that direct administration of flurbiprofen in a microparticle formulation at a site of tissue injury delays the onset and lowers the intensity of postoperative pain at lower doses than usually administered orally. JF - Journal of clinical pharmacology AU - Dionne, Raymond A AU - Haynes, Duncan AU - Brahim, Jaime S AU - Rowan, Janet S AU - Guivarc'h, Pol-Henri AD - National Institute of Dental and Craniofacial Research, National Institute of Health, 10 Center Drive, 1N-103, Bethesda, MD 20892-1197, USA. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 1418 EP - 1424 VL - 44 IS - 12 SN - 0091-2700, 0091-2700 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - Delayed-Action Preparations KW - Flurbiprofen KW - 5GRO578KLP KW - Index Medicus KW - Chemistry, Pharmaceutical -- classification KW - Periodontium -- surgery KW - Anti-Inflammatory Agents, Non-Steroidal -- therapeutic use KW - Pain Measurement -- methods KW - Pain, Postoperative -- etiology KW - Dose-Response Relationship, Drug KW - Humans KW - Particle Size KW - Periodontium -- injuries KW - Chemistry, Pharmaceutical -- methods KW - Pain, Postoperative -- classification KW - Pain, Postoperative -- drug therapy KW - Periodontium -- drug effects KW - Treatment Outcome KW - Peripheral Nerves -- drug effects KW - Peripheral Nerves -- physiology KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology KW - Dental Models KW - Delayed-Action Preparations -- therapeutic use KW - Flurbiprofen -- therapeutic use KW - Delayed-Action Preparations -- pharmacokinetics KW - Surgery, Oral KW - Flurbiprofen -- pharmacology KW - Delayed-Action Preparations -- administration & dosage KW - Analgesia -- methods KW - Administration, Topical KW - Flurbiprofen -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67072657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+pharmacology&rft.atitle=Analgesic+effect+of+sustained-release+flurbiprofen+administered+at+the+site+of+tissue+injury+in+the+oral+surgery+model.&rft.au=Dionne%2C+Raymond+A%3BHaynes%2C+Duncan%3BBrahim%2C+Jaime+S%3BRowan%2C+Janet+S%3BGuivarc%27h%2C+Pol-Henri&rft.aulast=Dionne&rft.aufirst=Raymond&rft.date=2004-12-01&rft.volume=44&rft.issue=12&rft.spage=1418&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+pharmacology&rft.issn=00912700&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-08 N1 - Date created - 2004-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucolipidosis IV. AN - 67063329; 15523648 AB - A patient with mucolipidosis-IV heterozygous for two mutations in MCOLN1 expressed only her father's cDNA mutation c.1207C>T predicting an R403C change in mucolipin. She inherited a 93bp segment from mitochondrial NADH dehydrogenase 5 (MTND5) from her mother that was inserted in-frame prior to the last nucleotide of exon 2 of MCOLN1 (c.236_237ins93). This alteration abolished proper splicing of MCOLN1. The splice site at the end of the exon was not used due to an inhibitory effect of the inserted segment, resulting in two aberrant splice products containing stop codons in the downstream intron. These products were eliminated via nonsense-mediated decay. This is the first report of an inherited transfer of mitochondrial nuclear DNA causing a genetic disease. The elimination of the splice site by the mitochondrial DNA requires a change in splicing prediction models. Copyright 2004 Wiley-Liss, Inc. JF - Human mutation AU - Goldin, Ehud AU - Stahl, Stefanie AU - Cooney, Adele M AU - Kaneski, Christine R AU - Gupta, Surya AU - Brady, Roscoe O AU - Ellis, James R AU - Schiffmann, Raphael AD - Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892-1260, USA. goldine@ninds.nih.gov Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 460 EP - 465 VL - 24 IS - 6 KW - DNA, Complementary KW - 0 KW - DNA, Mitochondrial KW - MCOLN1 protein, human KW - Membrane Proteins KW - TRPM Cation Channels KW - Transient Receptor Potential Channels KW - Index Medicus KW - DNA Mutational Analysis KW - Humans KW - Mutation, Missense KW - Child, Preschool KW - RNA Splicing -- genetics KW - Base Sequence KW - Models, Genetic KW - Molecular Sequence Data KW - Female KW - Mutagenesis, Insertional KW - Membrane Proteins -- genetics KW - Mucolipidoses -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67063329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+mutation&rft.atitle=Transfer+of+a+mitochondrial+DNA+fragment+to+MCOLN1+causes+an+inherited+case+of+mucolipidosis+IV.&rft.au=Goldin%2C+Ehud%3BStahl%2C+Stefanie%3BCooney%2C+Adele+M%3BKaneski%2C+Christine+R%3BGupta%2C+Surya%3BBrady%2C+Roscoe+O%3BEllis%2C+James+R%3BSchiffmann%2C+Raphael&rft.aulast=Goldin&rft.aufirst=Ehud&rft.date=2004-12-01&rft.volume=24&rft.issue=6&rft.spage=460&rft.isbn=&rft.btitle=&rft.title=Human+mutation&rft.issn=1098-1004&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-24 N1 - Date created - 2004-11-11 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 25650; OMIM; 516005; 605248 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Simian parvovirus infection: a potential zoonosis. AN - 67050210; 15529252 AB - Simian parvovirus (SPV) causes severe anemia in immunocompromised macaques. The closely related erythrovirus, parvovirus B19, causes anemia in susceptible humans and can be grown in human bone marrow mononuclear cells in vitro. We hypothesized that SPV may infect humans and replicate in human bone marrow mononuclear cells. Serum samples from handlers of an SPV-seropositive macaque colony were tested by Western blot for evidence of antibodies to SPV. SPV capsid protein was expressed in insect cells, and SPV was cultured in human and macaque bone marrow mononuclear cells. Fifty-one percent of exposed handlers (n=65) were found to be SPV seropositive, compared with 35% of nonexposed individuals (n=124). In 17% of exposed handlers, compared with 6% of nonexposed individuals, antibodies were directed to SPV but not to B19. SPV capsid proteins, like those of B19, self-assembled to form parvovirus-like particles, and these capsids, like B19 capsids, bound to globoside, suggesting that globoside is also the receptor for SPV. We demonstrated that SPV could replicate in vitro in both human and macaque bone marrow mononuclear cells and that it was cytotoxic to erythroid progenitor cells. Our data suggest that SPV may infect human bone marrow mononuclear cells in vitro and in vivo and should be considered a potential zoonosis. JF - The Journal of infectious diseases AU - Brown, Kevin E AU - Liu, Zhengwen AU - Gallinella, Giorgio AU - Wong, Susan AU - Mills, Ian P AU - O'Sullivan, M Gerard AD - Hematology Branch, National Heart, Lung, and Blood Institute, Building 10, Room CRC-3-5130, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-1202, USA. brownk@nhlbi.nih.gov Y1 - 2004/12/01/ PY - 2004 DA - 2004 Dec 01 SP - 1900 EP - 1907 VL - 190 IS - 11 SN - 0022-1899, 0022-1899 KW - Antibodies, Viral KW - 0 KW - Capsid Proteins KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Macaca KW - Seroepidemiologic Studies KW - Parvovirus B19, Human -- metabolism KW - Capsid Proteins -- genetics KW - Capsid Proteins -- biosynthesis KW - Parvovirus B19, Human -- genetics KW - Zoonoses KW - Blotting, Western KW - Cells, Cultured KW - Risk Factors KW - Cohort Studies KW - Species Specificity KW - Erythrovirus -- growth & development KW - Antibodies, Viral -- blood KW - Bone Marrow Cells -- metabolism KW - Parvoviridae Infections -- blood KW - Erythrovirus -- isolation & purification KW - Parvoviridae Infections -- epidemiology KW - Occupational Diseases -- blood KW - Bone Marrow Cells -- virology KW - Occupational Diseases -- epidemiology KW - Erythrovirus -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67050210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Simian+parvovirus+infection%3A+a+potential+zoonosis.&rft.au=Brown%2C+Kevin+E%3BLiu%2C+Zhengwen%3BGallinella%2C+Giorgio%3BWong%2C+Susan%3BMills%2C+Ian+P%3BO%27Sullivan%2C+M+Gerard&rft.aulast=Brown&rft.aufirst=Kevin&rft.date=2004-12-01&rft.volume=190&rft.issue=11&rft.spage=1900&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 - 2004-12-30 N1 - Date created - 2004-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Crystallography and mutagenesis point to an essential role for the N-terminus of human mitochondrial ClpP. AN - 67039471; 15522782 AB - We have determined a 2.1 A crystal structure for human mitochondrial ClpP (hClpP), the proteolytic component of the ATP-dependent ClpXP protease. HClpP has a structure similar to that of the bacterial enzyme, with the proteolytic active sites sequestered within an aqueous chamber formed by face-to-face assembly of the two heptameric rings. The hydrophobic N-terminal peptides of the subunits are bound within the narrow (12 A) axial channel, positioned to interact with unfolded substrates translocated there by the associated ClpX chaperone. Mutation or deletion of these residues causes a drastic decrease in ClpX-mediated protein and peptide degradation. Residues 8-16 form a mobile loop that extends above the ring surface and is also required for activity. The 28 amino acid C-terminal domain, a unique feature of mammalian ClpP proteins, lies on the periphery of the ring, with its proximal portion forming a loop that extends out from the ring surface. Residues at the start of the C-terminal domain impinge on subunit interfaces within the ring and affect heptamer assembly and stability. We propose that the N-terminal peptide of ClpP is a structural component of the substrate translocation channel and may play an important functional role as well. JF - Journal of structural biology AU - Kang, Sung Gyun AU - Maurizi, Michael R AU - Thompson, Mark AU - Mueser, Timothy AU - Ahvazi, Bijan AD - Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 338 EP - 352 VL - 148 IS - 3 SN - 1047-8477, 1047-8477 KW - Escherichia coli Proteins KW - 0 KW - Peptides KW - ClpP protease, E coli KW - EC 3.4.21.92 KW - Endopeptidase Clp KW - Index Medicus KW - Protein Structure, Secondary KW - Dose-Response Relationship, Drug KW - Models, Molecular KW - Humans KW - Amino Acid Sequence KW - Binding Sites KW - Gene Deletion KW - Mutagenesis, Site-Directed KW - Kinetics KW - Molecular Sequence Data KW - Peptides -- chemistry KW - Crystallography, X-Ray KW - Sequence Homology, Amino Acid KW - Protein Structure, Tertiary KW - Mutation KW - Protein Conformation KW - Catalysis KW - Escherichia coli Proteins -- chemistry KW - Endopeptidase Clp -- physiology KW - Mitochondria -- enzymology KW - Mitochondria -- metabolism KW - Endopeptidase Clp -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67039471?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+structural+biology&rft.atitle=Crystallography+and+mutagenesis+point+to+an+essential+role+for+the+N-terminus+of+human+mitochondrial+ClpP.&rft.au=Kang%2C+Sung+Gyun%3BMaurizi%2C+Michael+R%3BThompson%2C+Mark%3BMueser%2C+Timothy%3BAhvazi%2C+Bijan&rft.aulast=Kang&rft.aufirst=Sung&rft.date=2004-12-01&rft.volume=16&rft.issue=4&rft.spage=185&rft.isbn=&rft.btitle=&rft.title=Deafness+and+Education+International&rft.issn=14643154&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-15 N1 - Date created - 2004-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BAY 50-4798, a novel, high-affinity receptor-specific recombinant interleukin-2 analog, induces dose-dependent increases in CD25 expression and proliferation among unstimulated, human peripheral blood mononuclear cells in vitro. AN - 67011950; 15507389 AB - Interleukin-2 administration induces CD4 T cell expansion in HIV-infected patients, however, toxicity can limit dosing. BAY 50-4798 is a recombinant IL-2 analog with >1000-fold specificity for the high-affinity IL-2 receptor. The effects of this compound on unstimulated human PBMC were evaluated. PBMC from HIV(-) and HIV(+) donors were cultured in vitro with incremental doses of BAY 50-4798 or aldesleukin. CD25 expression and proliferation were evaluated with flow cytometry. Cytokine levels were measured by ELISA in culture supernatants. BAY 50-4798 induced dose-dependent increases in CD25 expression and proliferation of T cells, NK, and B cells and showed selectivity for CD4 T cells expressing CD25. Induction of pro-inflammatory cytokines was also dose-dependent and was observed at the concentrations of BAY 50-4798 with the highest biologic activity. These data suggest that BAY 50-4798 can induce proliferation of unstimulated T cells but loss of T cell selectivity and induction of pro-inflammatory cytokines occur at concentrations exerting the highest biologic activity. JF - Clinical immunology (Orlando, Fla.) AU - Matthews, Lynn AU - Chapman, Sherita AU - Ramchandani, Meena S AU - Lane, H Clifford AU - Davey, Richard T AU - Sereti, Irini AD - Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 248 EP - 255 VL - 113 IS - 3 SN - 1521-6616, 1521-6616 KW - Interleukin-2 KW - 0 KW - Ki-67 Antigen KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - aldesleukin KW - M89N0Q7EQR KW - Index Medicus KW - Cell Proliferation -- drug effects KW - B-Lymphocytes -- cytology KW - Dose-Response Relationship, Drug KW - Humans KW - Ki-67 Antigen -- metabolism KW - B-Lymphocytes -- immunology KW - Killer Cells, Natural -- cytology KW - B-Lymphocytes -- metabolism KW - HIV Infections -- pathology KW - Killer Cells, Natural -- drug effects KW - B-Lymphocytes -- drug effects KW - T-Lymphocytes -- metabolism KW - Cells, Cultured KW - HIV Infections -- immunology KW - Up-Regulation -- drug effects KW - Inflammation -- immunology KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- virology KW - Killer Cells, Natural -- metabolism KW - T-Lymphocytes -- immunology KW - Killer Cells, Natural -- immunology KW - Interleukin-2 -- pharmacology KW - Receptors, Interleukin-2 -- metabolism KW - Recombinant Proteins -- pharmacology KW - Interleukin-2 -- analogs & derivatives KW - Leukocytes, Mononuclear -- virology KW - Leukocytes, Mononuclear -- metabolism KW - Leukocytes, Mononuclear -- drug effects KW - Leukocytes, Mononuclear -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67011950?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+immunology+%28Orlando%2C+Fla.%29&rft.atitle=BAY+50-4798%2C+a+novel%2C+high-affinity+receptor-specific+recombinant+interleukin-2+analog%2C+induces+dose-dependent+increases+in+CD25+expression+and+proliferation+among+unstimulated%2C+human+peripheral+blood+mononuclear+cells+in+vitro.&rft.au=Matthews%2C+Lynn%3BChapman%2C+Sherita%3BRamchandani%2C+Meena+S%3BLane%2C+H+Clifford%3BDavey%2C+Richard+T%3BSereti%2C+Irini&rft.aulast=Matthews&rft.aufirst=Lynn&rft.date=2004-12-01&rft.volume=113&rft.issue=3&rft.spage=248&rft.isbn=&rft.btitle=&rft.title=Clinical+immunology+%28Orlando%2C+Fla.%29&rft.issn=15216616&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-15 N1 - Date created - 2004-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Peroxisome proliferator-activated receptor alpha regulates B lymphocyte development via an indirect pathway in mice. AN - 66996027; 15498504 AB - Peroxisome proliferator-activator receptor alpha (PPARalpha), a member of the nuclear receptor superfamily, has been implicated in the regulation of inflammation and immune response. Adaptive immune responses are suppressed by exposure to PPARalpha agonists, resulting in severe thymus and spleen atrophy. In addition, the decline in both T and B cells is due in part to the loss of splenocytes upon exposure to PPARalpha agonists. Thus, the current study was designed to examine the effect of Wy-14,643, a potent PPARalpha agonist, on B cell development in bone marrow from wild-type and PPARalpha-null mice. Significantly decrease in pro/pre-B cell and total B220(+) cell was observed in wild-type mice in bone marrow upon Wy-14,643 treatment, but not in PPARalpha-null mice. Immature and mature B cell populations are not affected. This suggests that PPARalpha is involved in the development of B cell during lymphoid lineage. However, surprisingly, PPARalpha mRNA was absent in bone marrow as revealed by RT-PCR. Therefore, the effect of PPARalpha on B cell development is by an indirect mechanism. JF - Biochemical pharmacology AU - Yang, Qian AU - Gonzalez, Frank J AD - Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Building 37, Room 3106B, Bethesda, MD 20892, USA. Y1 - 2004/12/01/ PY - 2004 DA - 2004 Dec 01 SP - 2143 EP - 2150 VL - 68 IS - 11 SN - 0006-2952, 0006-2952 KW - PPAR alpha KW - 0 KW - Pyrimidines KW - RNA, Messenger KW - pirinixic acid KW - 86C4MRT55A KW - Index Medicus KW - Animals KW - RNA, Messenger -- metabolism KW - Pyrimidines -- pharmacology KW - Bone Marrow -- metabolism KW - Mice KW - Myeloid Cells -- physiology KW - Myeloid Cells -- drug effects KW - Mice, Knockout KW - B-Lymphocytes -- drug effects KW - PPAR alpha -- physiology KW - B-Lymphocytes -- physiology KW - PPAR alpha -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66996027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Peroxisome+proliferator-activated+receptor+alpha+regulates+B+lymphocyte+development+via+an+indirect+pathway+in+mice.&rft.au=Yang%2C+Qian%3BGonzalez%2C+Frank+J&rft.aulast=Yang&rft.aufirst=Qian&rft.date=2004-12-01&rft.volume=68&rft.issue=11&rft.spage=2143&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 - 2005-02-28 N1 - Date created - 2004-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A multistate trial of pharmacy syringe purchase. AN - 66945162; 15466847 AB - Pharmacies are a potential site for access to sterile syringes as a means for preventing human immunodeficiency virus (HIV), but the type and extent of their utility is uncertain. To examine pharmacy syringe purchase, we conducted a standardized, multistate study in urban and rural areas of four states in which attempts to purchase syringes were documented. Of 1,600 overall purchase attempts, 35% were refused. Colorado (25%) and Connecticut (28%) had significantly lower rates of refusal than Kentucky (41%) and Missouri (47%). Furthermore, urban settings had higher rates of refusal (40%) than rural settings (31%, P < .01). Race and gender did not have a consistent impact on rates of refusal. Despite potential advantages of pharmacies as sites for access to sterile syringes, pharmacy purchase of syringes faces significant obstacles in terms of the practices in different jurisdictions. JF - Journal of urban health : bulletin of the New York Academy of Medicine AU - Compton, Wilson M AU - Horton, Joe C AU - Cottler, Linda B AU - Booth, Robert AU - Leukefeld, Carl G AU - Singer, Merrill AU - Cunningham-Williams, Renee AU - Reich, Wendy AU - Fortuin Corsi, Karen AU - Staton, Michele AU - Fink, Joseph L AU - Stopka, Thomas J AU - Spitznagel, Edward L AD - National Institute on Drug Abuse, 6001 Executive Boulevard, MSC 9589, Bethesda, MD 20892-9589, USA. wcompton@nida.nih.gov. Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 661 EP - 670 VL - 81 IS - 4 SN - 1099-3460, 1099-3460 KW - Index Medicus KW - United States KW - HIV Infections KW - Humans KW - Surveys and Questionnaires KW - Substance-Related Disorders KW - Male KW - Female KW - Pharmacies KW - Syringes -- supply & distribution KW - Commerce UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66945162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infants+and+Young+Children&rft.atitle=Mission+I%27m+Possible%3A+Effects+of+a+Community-Based+Project+on+the+Basic+Literacy+Skills+of+At-Risk+Kindergarteners&rft.au=Chong%2C+Wan+Har%3BMoore%2C+Dennis+W.%3BNonis%2C+Karen+P.%3BTang%2C+Hui+Nee%3BKoh%2C+Patricia%3BWee%2C+Sharon&rft.aulast=Chong&rft.aufirst=Wan&rft.date=2014-01-01&rft.volume=27&rft.issue=1&rft.spage=60&rft.isbn=&rft.btitle=&rft.title=Infants+and+Young+Children&rft.issn=08963746&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-10 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Public Health. 2001 May;91(5):791-3 [11344889] Eur Addict Res. 2001 Mar;7(1):40-5 [11316925] Subst Use Misuse. 2001 Apr;36(5):535-50 [11419486] J Acquir Immune Defic Syndr. 2001 Aug 1;27(4):398-404 [11468429] J Urban Health. 2001 Dec;78(4):679-89 [11796814] J Public Health Policy. 2002;23(3):324-43 [12325289] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S6-9 [12489602] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S10-2 [12489603] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S13-8 [12489604] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S19-20 [12489605] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S34-9 [12489613] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S40-5 [12489614] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S46-51 [12489615] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S52-7 [12489616] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S62-7 [12489618] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S68-72 [12489619] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S77-82 [12489621] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S83-7 [12489622] J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6 Suppl 2):S94-8 [12489625] Body Posit. 2003 Jan-Feb;16(1):15-7 [12739507] Am J Public Health. 1992 Apr;82(4):595-6 [1546784] JAMA. 1997 Sep 17;278(11):946-7 [9302251] Public Health Rep. 1998 Jun;113 Suppl 1:81-9 [9722813] J Urban Health. 2000 Mar;77(1):113-20 [10741847] J Acquir Immune Defic Syndr. 2001 Jun 1;27(2):183-92 [11404541] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estrogen receptor-alpha mediates the detrimental effects of neonatal diethylstilbestrol (DES) exposure in the murine reproductive tract. AN - 66932620; 15458790 AB - It is generally believed that estrogen receptor-dependent and -independent pathways are involved in mediating the developmental effects of the synthetic estrogen, diethylstilbestrol (DES). However, the precise role and extent to which each pathway contributes to the resulting pathologies remains unknown. We have employed the estrogen receptor knockout (ERKO) mice, which lack either estrogen receptor-alpha (alphaERKO or estrogen receptor-beta (betaERKO), to gain insight into the contribution of each ER-dependent pathway in mediating the effects of neonatal DES exposure in the female and male reproductive tract tissues of the mouse. Estrogen receptor-alpha female mice exhibited complete resistance to the chronic effects of neonatal DES exposure that were obvious in exposed wild-type animals, including atrophy and epithelial squamous metaplasia in the uterus; proliferative lesions of the oviduct; and persistent cornification of the vaginal epithelium. DES-mediated reduction in uterine Hoxa10, Hoxa11 and Wnt7a expression that occurs wild-type females during the time of exposure was also absent in alphaERKO females. In the male, alphaERKO mice exhibited complete resistance to the chronic effects of neonatal DES exposure on the prostate, including decreased androgen receptor levels, epithelial hyperplasia, and increased basal cell proliferation. Although ERbeta is highly expressed in the prostate epithelium, DES-exposed betaERKO males exhibited all of the effects of neonatal DES exposure that were observed in similarly exposed wild-type males. Therefore, the lack of DES-effects on gene expression and tissue differentiation in the alphaERKO uterus and prostate provides unequivocal evidence of an obligatory role for ERalpha in mediating the detrimental actions of neonatal DES exposure in the murine reproductive tract. JF - Toxicology AU - Couse, John F AU - Korach, Kenneth S AD - Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, PO Box 12233, MD B3-02, NC 27709, USA. Y1 - 2004/12/01/ PY - 2004 DA - 2004 Dec 01 SP - 55 EP - 63 VL - 205 IS - 1-2 SN - 0300-483X, 0300-483X KW - Estrogen Receptor alpha KW - 0 KW - Estrogen Receptor beta KW - Diethylstilbestrol KW - 731DCA35BT KW - Index Medicus KW - Animals, Newborn KW - Animals KW - Estrogen Receptor beta -- physiology KW - Mice KW - Male KW - Female KW - Mice, Knockout KW - Genitalia -- drug effects KW - Genitalia -- pathology KW - Diethylstilbestrol -- toxicity KW - Genitalia -- metabolism KW - Estrogen Receptor alpha -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66932620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Estrogen+receptor-alpha+mediates+the+detrimental+effects+of+neonatal+diethylstilbestrol+%28DES%29+exposure+in+the+murine+reproductive+tract.&rft.au=Couse%2C+John+F%3BKorach%2C+Kenneth+S&rft.aulast=Couse&rft.aufirst=John&rft.date=2004-12-01&rft.volume=205&rft.issue=1-2&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-23 N1 - Date created - 2004-10-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fathers' and mothers' parenting behavior and beliefs as predictors of children's social adjustment in the transition to school AN - 57170571; 341035 AB - The current study focuses on the association between children's social adjustment in the transition to school and the early elementary school years and their fathers' and mothers' parenting behaviors and beliefs and quality of marital relationship. The authors found that the most competent and least problematic children from the teachers' perspectives are those whose fathers are sensitive and supportive of their children's autonomy, whose mothers' parenting beliefs support self-directed child behavior, and whose parents maintain an emotionally intimate relationship. These findings have implications for efforts to prevent early school problems in children and support the children's transitions into formal schooling. (Original abstract) JF - Journal of Family Psychology 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 - 2004/12// PY - 2004 DA - December 2004 SP - 628 EP - 638 VL - 18 IS - 4 SN - 0893-3200, 0893-3200 KW - Parenting style KW - USA KW - Predictors KW - Young children KW - Parent-Child relationships KW - School adjustment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57170571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Family+Psychology&rft.atitle=Fathers%27+and+mothers%27+parenting+behavior+and+beliefs+as+predictors+of+children%27s+social+adjustment+in+the+transition+to+school&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=2004-12-01&rft.volume=18&rft.issue=4&rft.spage=628&rft.isbn=&rft.btitle=&rft.title=Journal+of+Family+Psychology&rft.issn=08933200&rft_id=info:doi/ LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2005-09-19 N1 - Document feature - refs. tbls. N1 - Last updated - 2016-09-27 N1 - SubjectsTermNotLitGenreText - Young children; School adjustment; Predictors; Parent-Child relationships; Parenting style; USA ER - TY - JOUR T1 - Are stem cells and T cells best transplanted separately? AN - 21286729; 7347684 JF - Cytotherapy AU - Barrett, John AD - Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 529 EP - 532 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 6 IS - 6 SN - 1465-3249, 1465-3249 KW - Biotechnology and Bioengineering Abstracts KW - Stem cells KW - Lymphocytes T KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21286729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Child+Psychology+and+Psychiatry&rft.atitle=Learning+to+Read+in+Williams+Syndrome+and+Down+Syndrome%3A+Syndrome-Specific+Precursors+and+Developmental+Trajectories&rft.au=Steele%2C+Ann%3BScerif%2C+Gaia%3BCornish%2C+Kim%3BKarmiloff-Smith%2C+Annette&rft.aulast=Steele&rft.aufirst=Ann&rft.date=2013-07-01&rft.volume=54&rft.issue=7&rft.spage=754&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Psychology+and+Psychiatry&rft.issn=00219630&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-03-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Stem cells; Lymphocytes T DO - http://dx.doi.org/10.1080/14653240410011927 ER - TY - JOUR T1 - Conditional Maximum Likelihood Estimation Following a Group Sequential Test AN - 21091810; 11132728 AB - We consider estimation after a group sequential test. An estimator that is unbiased or has small bias may have substantial conditional bias (Troendle and Yu, 1999, Coburger and Wassmer, 2001). In this paper we derive the conditional maximum likelihood estimators of both the primary parameter and a secondary parameter, and investigate their properties within a conditional inference framework. The method applies to both the usual and adaptive group sequential test designs. JF - Biometrical Journal AU - Liu, Aiyi AU - Troendle, James F AU - Yu, Kai F AU - Yuan, Vivian W AD - Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, Department of Health and Human Services, 6100 Executive Blvd., Rockville, MD 20852, USA, liua@mail.nih.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 760 EP - 768 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 USA VL - 46 IS - 6 SN - 0323-3847, 0323-3847 KW - Biotechnology and Bioengineering Abstracts KW - Statistics KW - Biometrics KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21091810?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Conditional+Maximum+Likelihood+Estimation+Following+a+Group+Sequential+Test&rft.au=Liu%2C+Aiyi%3BTroendle%2C+James+F%3BYu%2C+Kai+F%3BYuan%2C+Vivian+W&rft.aulast=Liu&rft.aufirst=Aiyi&rft.date=2004-12-01&rft.volume=46&rft.issue=6&rft.spage=760&rft.isbn=&rft.btitle=&rft.title=Biometrical+Journal&rft.issn=03233847&rft_id=info:doi/10.1002%2Fbimj.200410076 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Biometrics; Statistics DO - http://dx.doi.org/10.1002/bimj.200410076 ER - TY - JOUR T1 - Long-Chain (n-3) Fatty Acid Intake and Risk of Cancers of the Breast and the Prostate: Recent Epidemiological Studies, Biological Mechanisms, and Directions for Future Research AN - 20712940; 6093628 AB - The association between dietary (n-3) fatty acids and hormone-responsive cancers continues to attract considerable attention in epidemiological, clinical, and experimental studies. We previously reviewed the epidemiological literature on the association between hormone-responsive cancers and the long- chain fatty acids eicosapentaenoic acid and docosahexaenoic acid. We concluded that the compelling evidence from ecological studies, animal models, and mechanistic experiments in vitro was not supported clearly by the available epidemiological data. To various degrees, epidemiological studies published more recently attempted to address some of the methodological limitations plaguing earlier studies by using validated questionnaires, examining specific fatty acids and their interrelationships, and adjusting estimates for a wider range of potentially confounding factors than in previous studies. In this review, our aim was to update the previous review with the results of recent epidemiological studies and to discuss possible biological mechanisms and directions for future research. JF - Journal of Nutrition AU - Terry, Paul D AU - Terry, Jennifer B AU - Rohan, Thomas E AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 3412S EP - 3420S PB - American Institute of Nutrition VL - 134 IS - 12 SN - 0022-3166, 0022-3166 KW - Risk Abstracts KW - Diets KW - Reviews KW - Fatty acids KW - Animal models KW - Cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20712940?accountid=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+Nutrition&rft.atitle=Long-Chain+%28n-3%29+Fatty+Acid+Intake+and+Risk+of+Cancers+of+the+Breast+and+the+Prostate%3A+Recent+Epidemiological+Studies%2C+Biological+Mechanisms%2C+and+Directions+for+Future+Research&rft.au=Terry%2C+Paul+D%3BTerry%2C+Jennifer+B%3BRohan%2C+Thomas+E&rft.aulast=Terry&rft.aufirst=Paul&rft.date=2004-12-01&rft.volume=134&rft.issue=12&rft.spage=3412S&rft.isbn=&rft.btitle=&rft.title=Journal+of+Nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-10-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Diets; Reviews; Animal models; Fatty acids; Cancer ER - TY - JOUR T1 - Using stem cells in multiple sclerosis therapies AN - 20470956; 7347697 AB - Stem cell transplantation approaches offer for the first time the opportunity to design therapeutic approaches for multiple sclerosis (MS) with curative intent. Here we discuss key observations and questions emerging from clinical trials of hematopoietic stem cell transplantation for MS and from studies of myelin/neural repair in experimental models of demyelinating disorders. JF - Cytotherapy AU - Muraro, P A AU - Cassiani-Ingoni, R AU - Martin, R AD - Neuroimmunology Branch, NINDS, NIH, Bethesda, Maryland, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 615 EP - 620 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 6 IS - 6 SN - 1465-3249, 1465-3249 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Myelin KW - Multiple sclerosis KW - Clinical trials KW - W 30920:Tissue Engineering KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20470956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotherapy&rft.atitle=Using+stem+cells+in+multiple+sclerosis+therapies&rft.au=Muraro%2C+P+A%3BCassiani-Ingoni%2C+R%3BMartin%2C+R&rft.aulast=Muraro&rft.aufirst=P&rft.date=2004-12-01&rft.volume=6&rft.issue=6&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/10.1080%2F14653240410005311 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-05-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Multiple sclerosis; Myelin; Clinical trials DO - http://dx.doi.org/10.1080/14653240410005311 ER - TY - JOUR T1 - Stem and progenitor cell therapies: insights from non-human primate models AN - 20250314; 7347691 AB - Genetic marking strategies in the non-human primate model have elucidated a number of principles relevant to implementation of clinical stem cell therapies, including the lineage potential, number and lifespan of hematopoietic stem and progenitor cells, and differences in the functional properties of marrow cells mobilized into the peripheral blood utilizing different regimens. JF - Cytotherapy AU - Dunbar, CE AD - Molecular Hematopoiesis Section, Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 586 EP - 588 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 6 IS - 6 SN - 1465-3249, 1465-3249 KW - Biotechnology and Bioengineering Abstracts KW - Stem cells KW - Life span KW - Hemopoiesis KW - Peripheral blood KW - Primates KW - W 30905:Medical Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20250314?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotherapy&rft.atitle=Stem+and+progenitor+cell+therapies%3A+insights+from+non-human+primate+models&rft.au=Dunbar%2C+CE&rft.aulast=Dunbar&rft.aufirst=CE&rft.date=2004-12-01&rft.volume=6&rft.issue=6&rft.spage=586&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/10.1080%2F14653240410005320 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Primates; Stem cells; Hemopoiesis; Peripheral blood; Life span DO - http://dx.doi.org/10.1080/14653240410005320 ER - TY - JOUR T1 - Cardiovascular potential of BM-derived stem and progenitor cells AN - 20249344; 7347695 AB - Observational and experimental studies suggest that BM-derived stem and progenitor cells may have the capacity to repair damaged cardiovascular tissue and initiate blood vessel growth in regions of ischemia. Despite controversies regarding transdifferentiation potential of adult stem cells, clinical trials are underway testing the hypothesis that BM cell-based approaches to a broad spectrum of cardiovascular diseases and disease presentations will be safe and effective strategies for patient management. JF - Cytotherapy AU - Cannon, RO AD - Cardiovascular Branch, NHLBI, NIH, Bethesda, Maryland, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 602 EP - 607 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 6 IS - 6 SN - 1465-3249, 1465-3249 KW - Biotechnology and Bioengineering Abstracts KW - Stem cells KW - Blood vessels KW - Hemopoiesis KW - Cardiovascular diseases KW - Ischemia KW - Clinical trials KW - W 30905:Medical Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20249344?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotherapy&rft.atitle=Cardiovascular+potential+of+BM-derived+stem+and+progenitor+cells&rft.au=Cannon%2C+RO&rft.aulast=Cannon&rft.aufirst=RO&rft.date=2004-12-01&rft.volume=6&rft.issue=6&rft.spage=602&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/10.1080%2F14653240410005294 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Stem cells; Ischemia; Hemopoiesis; Blood vessels; Clinical trials; Cardiovascular diseases DO - http://dx.doi.org/10.1080/14653240410005294 ER - TY - JOUR T1 - Delivery and tracking of therapeutic cell preparations for clinical cardiovascular applications AN - 20247795; 7347696 AB - Experimental observations suggesting adult stem cell plasticity and cross- lineage transdifferentiation have underpinned the investigation of cell therapy for cardiovascular disease. Many challenges still face the full realization of cardiovascular regenerative medicine. This brief review will highlight some of these, with emphasis on the choice of cell preparation, route of cell delivery and tracking of delivered cells. JF - Cytotherapy AU - De Silva, R AU - Lederman, R J AD - Cardiovascular Branch, National Heart Lung and Blood Institute, NIH, Bethesda, Maryland, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 608 EP - 614 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 6 IS - 6 SN - 1465-3249, 1465-3249 KW - Biotechnology and Bioengineering Abstracts KW - Stem cells KW - Reviews KW - Cardiovascular diseases KW - Plasticity KW - W 30905:Medical Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20247795?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotherapy&rft.atitle=Delivery+and+tracking+of+therapeutic+cell+preparations+for+clinical+cardiovascular+applications&rft.au=De+Silva%2C+R%3BLederman%2C+R+J&rft.aulast=De+Silva&rft.aufirst=R&rft.date=2004-12-01&rft.volume=6&rft.issue=6&rft.spage=608&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/10.1080%2F14653240410005339 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Plasticity; Cardiovascular diseases; Stem cells DO - http://dx.doi.org/10.1080/14653240410005339 ER - TY - JOUR T1 - Using Endogenous Neural Stem Cells to Enhance Recovery from Ischemic Brain Injury AN - 20014703; 7733071 AB - The use of cell-based therapy may be a valid therapeutic approach to ischemic brain injury. Stem cells have been proposed as a new form of cell based therapy in a variety of disorders, including acute and degenerative brain diseases. Up to date most efforts have concentrated on transplantation of embryonic stem cells (ESC) or neural stem cells (NSCs) obtained from immortalized cell lines into the diseased brain. These procedures require harvesting the appropriate stem cell, expansion in vitro and transplantation. Endogenous NSCs have been identified in the central nervous system where they reside largely in the subventricular zone and in the subgranular zone of the hippocampus. Endogenous NSCs may be capable of self-renewal and differentiation into functional glia and neurons. Manipulation of endogenous NSCs may bypass the need to use ESC as a form of therapy thus avoiding the complex ethical and biological issues involved with ES cells or immortalized cell lines. This review summarizes the evidence recently gathered in support of a therapeutic role for endogenous NSCs in acute experimental stroke. JF - Current Neurovascular Research AU - Leker, Ronen R AU - McKay, RDG AD - Laboratory of Molecular Biology, NIH / NINDS Building 36, room 3c12, 36 Convent Drive, MSC 4092, Bethesda, MD 20892, USA. Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 421 EP - 427 PB - Bentham Science Publishers B.V., P.O. Box 1673 Hilversum 1200 BR The Netherlands, [mailto:shidding@worldonline.nl], [URL:http://www.bentham.org] VL - 1 IS - 5 SN - 1567-2026, 1567-2026 KW - Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - neural stem cells KW - neurogenesis KW - stroke KW - ischemia KW - growth-factors KW - Central nervous system KW - Transplantation KW - Brain injury KW - Hippocampus KW - subventricular zone KW - Stroke KW - Ischemia KW - Differentiation KW - Stem cells KW - Embryo cells KW - Neurons KW - Ethics KW - Reviews KW - Glia KW - Neural stem cells KW - Harvesting KW - N3 11001:Behavioral and Cognitive Neuroscience KW - W 30945:Fermentation & Cell Culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20014703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Neurovascular+Research&rft.atitle=Using+Endogenous+Neural+Stem+Cells+to+Enhance+Recovery+from+Ischemic+Brain+Injury&rft.au=Leker%2C+Ronen+R%3BMcKay%2C+RDG&rft.aulast=Leker&rft.aufirst=Ronen&rft.date=2004-12-01&rft.volume=1&rft.issue=5&rft.spage=421&rft.isbn=&rft.btitle=&rft.title=Current+Neurovascular+Research&rft.issn=15672026&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-12-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Central nervous system; Brain injury; Transplantation; Hippocampus; subventricular zone; Stroke; Ischemia; Differentiation; Stem cells; Embryo cells; Reviews; Ethics; Neurons; Glia; Neural stem cells; Harvesting ER - TY - JOUR T1 - Factors affecting engraftment of allogeneic hematopoietic stem cells after reduced-intensity conditioning AN - 19984070; 7347692 AB - Several factors influence the engraftment of allogeneic hematopoietic stem cells (HSC). Recently, there has been increased utilization of transplant- conditioning regimens that use reduced doses of chemotherapy and radiation that are considered to be non-myeloablative. These non-myeloablative (or reduced- intensity) allogeneic HSC transplants (RIST) decrease early post-transplant complications, but they are associated with higher incidences of mixed chimerism and graft rejection compared with transplantation after myeloablative conditioning. RIST provides a unique opportunity to study allogeneic HSC engraftment. In particular, host immune status and stem cell graft composition have emerged as important factors affecting engraftment after RIST. Based on these observations, it has been hypothesized that conditioning regimens and allograft composition can be tailored to an individual patients immune and disease status prior to transplant. JF - Cytotherapy AU - Walshe, J AU - Bishop, M R AD - Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 589 EP - 592 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 6 IS - 6 SN - 1465-3249, 1465-3249 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts KW - Immune status KW - Stem cells KW - Radiation KW - Graft rejection KW - Chemotherapy KW - Chimerism KW - W 30965:Miscellaneous, Reviews KW - F 06920:Transplantation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19984070?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotherapy&rft.atitle=Factors+affecting+engraftment+of+allogeneic+hematopoietic+stem+cells+after+reduced-intensity+conditioning&rft.au=Walshe%2C+J%3BBishop%2C+M+R&rft.aulast=Walshe&rft.aufirst=J&rft.date=2004-12-01&rft.volume=6&rft.issue=6&rft.spage=589&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/10.1080%2F14653240410005285 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-05-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Immune status; Stem cells; Graft rejection; Radiation; Chemotherapy; Chimerism DO - http://dx.doi.org/10.1080/14653240410005285 ER - TY - JOUR T1 - Possible role of Stat5a in rat mammary gland carcinogenesis AN - 19819067; 6382349 AB - Signal transducer and activator of transcription (Stat) 5a is a transcription factor mediating the action of specific cytokines, growth factors and hormones on gene expression. In the mammary gland, Stat5a is well recognized for its function in prolactin signaling, lobuloalveolar development, and milk protein expression during pregnancy and lactation. Latent cytoplasmic Stat5a is activated by tyrosine phosphorylation and following dimerization undergoes nuclear import. In the current study, Stat5a expression was examined immunohistochemically in carcinomas induced by the chemical carcinogens 7,12-dimethylbenz[a]anthracene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. A high percentage of carcinomas showed nuclear labeling of Stat5a [44 of 68 (65%)] with Stat5a nuclear labeling index ranging from 18 to 77%. In contrast, control normal mammary gland tissue displayed cytosolic expression. Carcinomas with different Stat5a staining patterns (cytoplasmic or nuclear) showed a statistical difference for the proliferating cell nuclear antigen (PCNA) labeling, tumor differentiation, nuclear grade, mitotic activity, and tumor size. High Stat5a nuclear expression was closely correlated with the higher-grade carcinomas. Stat5a nuclear expression was also detected in intraductal proliferations (10 of 21 lesions) and in ductal carcinomas in situ (13 of 15 lesions). Immunohistochemical analysis was further carried out in human breast cancers. Stat5a nuclear expression was detected in ductal and lobular carcinomas and DCIS at a frequency of 48% (15/31), 33% (2/6), and 40% (2/5), respectively. Nuclear expression of Stat5a in human breast cancers also correlated with the PCNA nuclear labeling index. The findings implicate activated Stat5a in mammary gland cancer development in the rat and human. JF - Breast Cancer Research and Treatment AU - Shan, Liang AU - Yu, Minshu AU - Clark, Bradly D AU - Snyderwine, Elizabeth G AD - CCR, NCI, Building 37, Room 4146, 37 Convent Dr., Bethesda, MD, 20892-4262, USA, elizabeth_snyderwine@nih.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 263 EP - 272 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 88 IS - 3 SN - 0167-6806, 0167-6806 KW - Toxicology Abstracts; Oncogenes & Growth Factors Abstracts KW - Statistics KW - Milk KW - Mammary gland KW - Tyrosine KW - Carcinogens KW - Tumors KW - Proliferating cell nuclear antigen KW - Hormones KW - Carcinoma KW - Pregnancy KW - Lactation KW - Prolactin KW - Gene expression KW - Nuclear transport KW - Differentiation KW - Phosphorylation KW - 9,10-Dimethyl-1,2-benzanthracene KW - Transcription factors KW - Carcinogenesis KW - Breast cancer KW - Cytokines KW - Growth factors KW - Signal transduction KW - X 24320:Food Additives & Contaminants KW - B 26640:Cell Cycle & DNA Repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19819067?accountid=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=Breast+Cancer+Research+and+Treatment&rft.atitle=Possible+role+of+Stat5a+in+rat+mammary+gland+carcinogenesis&rft.au=Shan%2C+Liang%3BYu%2C+Minshu%3BClark%2C+Bradly+D%3BSnyderwine%2C+Elizabeth+G&rft.aulast=Shan&rft.aufirst=Liang&rft.date=2004-12-01&rft.volume=88&rft.issue=3&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Breast+Cancer+Research+and+Treatment&rft.issn=01676806&rft_id=info:doi/10.1007%2Fs10549-004-0805-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-06-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Milk; Statistics; Mammary gland; Tyrosine; Tumors; Carcinogens; Proliferating cell nuclear antigen; Hormones; Lactation; Pregnancy; Carcinoma; Gene expression; Prolactin; Differentiation; Nuclear transport; Phosphorylation; Transcription factors; 9,10-Dimethyl-1,2-benzanthracene; Carcinogenesis; Cytokines; Breast cancer; Growth factors; Signal transduction DO - http://dx.doi.org/10.1007/s10549-004-0805-2 ER - TY - JOUR T1 - Echocardiographic Findings in the PANDAS Subgroup AN - 19816340; 6099710 AB - BACKGROUND: Sydenham's chorea is the neurologic manifestation of rheumatic fever and is a diagnosis of exclusion requiring only the presence of frank chorea in the absence of another neurologic disorder. Two thirds of children with Sydenham's chorea also have rheumatic carditis (pathologic mitral valve regurgitation). Although there are similar neuropsychiatric symptoms and preceding group A beta-hemolytic streptococcal infection associated with both Sydenham's chorea and the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) subgroup, it is unknown whether patients in the PANDAS subgroup have any cardiac involvement. METHODS: Sixty children meeting the criteria for PANDAS were entered into protocols at National Institute of Mental Health between 1993 and 2002. Doppler and 2- dimensional echocardiograms were performed on these subjects to assess valvular heart disease. RESULTS: Of these 60 children, no echocardiographic evidence of significant mitral or aortic valve regurgitation was found. One patient was found to have mild mitral regurgitation, and all patients had normal left atrial size and normal left ventricular size and function. Follow-up echocardiograms on 20 children showed no significant valvular regurgitation. CONCLUSION: The evidence of a clear lack of rheumatic carditis in these children supports the hypothesis that PANDAS is a distinct neuropsychiatric diagnosis separate from Sydenham's chorea. JF - Pediatrics AU - Snider, Lisa A AU - Sachdev, Vandana AU - Mackaronis, Julia E AU - Peter, Marilyn St AU - Swedo, Susan E AD - Pediatrics and Developmental Neuropsychiatry Branch, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services. National Heart Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - e748 EP - e751 PB - American Academy of Pediatrics, 141 Northwest Point Blvd. Elk Grove Village IL 60007-1098 USA, [mailto:journals@aap.org], [URL:http://www.aap.org] VL - 114 IS - 6 SN - 0031-4005, 0031-4005 KW - Microbiology Abstracts B: Bacteriology KW - Streptococcus KW - Heart KW - Rheumatic fever KW - Aortic valve KW - Pediatrics KW - Echocardiography KW - Infection KW - Children KW - Mitral valve KW - Chorea KW - Ventricle KW - Mental disorders KW - Regurgitation KW - Carditis KW - Heart diseases KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19816340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pediatrics&rft.atitle=Echocardiographic+Findings+in+the+PANDAS+Subgroup&rft.au=Snider%2C+Lisa+A%3BSachdev%2C+Vandana%3BMackaronis%2C+Julia+E%3BPeter%2C+Marilyn+St%3BSwedo%2C+Susan+E&rft.aulast=Snider&rft.aufirst=Lisa&rft.date=2004-12-01&rft.volume=114&rft.issue=6&rft.spage=e748&rft.isbn=&rft.btitle=&rft.title=Pediatrics&rft.issn=00314005&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 - Heart; Rheumatic fever; Pediatrics; Aortic valve; Echocardiography; Children; Infection; Mitral valve; Chorea; Mental disorders; Ventricle; Regurgitation; Carditis; Heart diseases; Streptococcus ER - TY - JOUR T1 - Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock AN - 19770446; 6092098 AB - During sepsis, limited data on the survival effects of vasopressors are available to guide therapy. Therefore, we compared the effects of three vasopressors on survival in a canine septic shock model. Seventy-eight awake dogs infected with differing doses of intraperitoneal Escherichia coli to produce increasing mortality were randomized to receive epinephrine (0.2, 0.8, or 2.0 mu g.kg super(-1).min super(-1)), norepinephrine (0.2, 1.0, or 2.0 mu g.kg super(- 1).min super(-1)), vasopressin (0.01 or 0.04 U/min), or placebo in addition to antibiotics and fluids. Serial hemodynamic and biochemical variables were measured. Increasing doses of bacteria caused progressively greater decreases in survival (P < 0.06), mean arterial pressure (MAP) (P < 0.05), cardiac index (CI) (P < 0.02), and ejection fraction (EF) (P = 0.02). The effects of epinephrine on survival were significantly different from those of norepinephrine and vasopressin (P = 0.03). Epinephrine had a harmful effect on survival that was significantly related to drug dose (P = 0.02) but not bacterial dose. Norepinephrine and vasopressin had beneficial effects on survival that were similar at all drug and bacteria doses. Compared with concurrent infected controls, epinephrine caused greater decreases in CI, EF, and pH, and greater increases in systemic vascular resistance and serum creatinine than norepinephrine and vasopressin. These epinephrine-induced changes were significantly related to the dose of epinephrine administered. In this study, the effects of vasopressors were independent of severity of infection but dependent on the type and dose of vasopressor used. Epinephrine adversely affected organ function, systemic perfusion, and survival compared with norepinephrine and vasopressin. In the ranges studied, norepinephrine and vasopressin have more favorable risk-benefit profiles than epinephrine during sepsis. JF - American Journal of Physiology: Heart and Circulatory Physiology AU - Minneci, Peter C AU - Deans, Katherine J AU - Banks, Steven M AU - Costello, Renee AU - Csako, Gyorgy AU - Eichacker, Peter Q AU - Danner, Robert L AU - Natanson, Charles AU - Solomon, Steven B AD - Critical Care Medicine Department and Department of Laboratory Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - H2545 EP - H2554 PB - American Physiological Society, 9650 Rockville Pike Bethesda MD 20814-3991 USA, [mailto:webmaster@the-aps.org], [URL:http://www.the-aps.org/] VL - 287 IS - 6 SN - 0363-6135, 0363-6135 KW - Microbiology Abstracts B: Bacteriology KW - Heart KW - Mortality KW - Perfusion KW - Data processing KW - Hemodynamics KW - Survival KW - Antibiotics KW - Septic shock KW - Infection KW - Blood pressure KW - Models KW - Sepsis KW - Creatinine KW - Vasopressin KW - Norepinephrine KW - Escherichia coli KW - Epinephrine KW - pH effects KW - Vascular system KW - J 02410:Animal Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19770446?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Physiology%3A+Heart+and+Circulatory+Physiology&rft.atitle=Differing+effects+of+epinephrine%2C+norepinephrine%2C+and+vasopressin+on+survival+in+a+canine+model+of+septic+shock&rft.au=Minneci%2C+Peter+C%3BDeans%2C+Katherine+J%3BBanks%2C+Steven+M%3BCostello%2C+Renee%3BCsako%2C+Gyorgy%3BEichacker%2C+Peter+Q%3BDanner%2C+Robert+L%3BNatanson%2C+Charles%3BSolomon%2C+Steven+B&rft.aulast=Minneci&rft.aufirst=Peter&rft.date=2004-12-01&rft.volume=287&rft.issue=6&rft.spage=H2545&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Physiology%3A+Heart+and+Circulatory+Physiology&rft.issn=03636135&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 - Heart; Mortality; Data processing; Perfusion; Survival; Hemodynamics; Antibiotics; Septic shock; Infection; Blood pressure; Models; Sepsis; Creatinine; Vasopressin; Norepinephrine; Epinephrine; pH effects; Vascular system; Escherichia coli ER - TY - JOUR T1 - Future Vaccine Development at NICHD AN - 19766720; 6244212 AB - Using published data and the results of our studies, we hypothesized that a critical level of serum IgG antibodies to the surface structures of invasive pathogens (capsular polysaccharides of Haemophilus influenzae type b, pneumococcus, meningococcus, Salmonella typhi, Escherichia coli, and Staphylococcus aureus, the O-specific polysaccharide LPS domain of the LPS of Shigella, non-typhoidal Salmonella, and E. coli, and the capsular polypeptide of Bacillus anthraces) confer immunity to these pathogens. Covalent attachment to a protein increases their immunogenicity and bestows T-cell properties to these antigens. We have also shown that a critical level of serum IgG antibodies to pertussis toxin alone induces immunity on both an individual and on a community basis (herd immunity) to Bordetella pertussis. It is likely that all the above conjugates and pertussis toxoid will be incorporated into vaccines for routine infant immunization. JF - Annals of the New York Academy of Sciences AU - Robbins, John B AU - Schneerson, Rachel AD - Chief, Laboratory of Developmental and Molecular Immunity, Chief, Section on Bacterial Disease, Pathogenesis and Immunity, Laboratory of Developmental and Molecular Immunity, NICHD, NIH, Bethesda, Maryland 20892, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 49 EP - 59 PB - New York Academy of Sciences, 2 East 63rd Street New York NY 10021 USA, [mailto:publications@nyas.org], [URL:http://www.nyas.org] VL - 1038 SN - 0077-8923, 0077-8923 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Pertussis KW - Haemophilus influenzae KW - Data processing KW - Salmonella typhi KW - Shigella KW - Neisseria meningitidis KW - Toxoids KW - Pathogens KW - Immunity KW - Immunization KW - pertussis toxin KW - Bordetella pertussis KW - Immunogenicity KW - Escherichia coli KW - Lymphocytes T KW - Immunoglobulin G KW - Lipopolysaccharides KW - Vaccines KW - Staphylococcus aureus KW - Bacillus KW - Capsular polysaccharides KW - Infants KW - F 06905:Vaccines KW - J 02350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19766720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Future+Vaccine+Development+at+NICHD&rft.au=Robbins%2C+John+B%3BSchneerson%2C+Rachel&rft.aulast=Robbins&rft.aufirst=John&rft.date=2004-12-01&rft.volume=1038&rft.issue=&rft.spage=49&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 revised - 2007-04-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Pertussis; Data processing; Immunity; Pathogens; Toxoids; Immunization; pertussis toxin; Immunogenicity; Immunoglobulin G; Lymphocytes T; Lipopolysaccharides; Vaccines; Capsular polysaccharides; Infants; Bordetella pertussis; Haemophilus influenzae; Salmonella typhi; Escherichia coli; Shigella; Neisseria meningitidis; Staphylococcus aureus; Bacillus ER - TY - JOUR T1 - Immortalization of mouse melanocytes carrying mutations in various pigmentation genes AN - 19734449; 7536405 JF - Analytical Biochemistry AU - Costin, Gertrude-E AU - Vieira, Wilfred D AU - Valencia, Julio C AU - Rouzaud, Francois AU - Lamoreux, M Lynn AU - Hearing, Vincent 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 - 2004/12// PY - 2004 DA - Dec 2004 SP - 171 EP - 174 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 335 IS - 1 SN - 0003-2697, 0003-2697 KW - Biotechnology and Bioengineering Abstracts KW - Pigmentation KW - Melanocytes KW - Mutation KW - Immortalization KW - W 30905:Medical Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19734449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Immortalization+of+mouse+melanocytes+carrying+mutations+in+various+pigmentation+genes&rft.au=Costin%2C+Gertrude-E%3BVieira%2C+Wilfred+D%3BValencia%2C+Julio+C%3BRouzaud%2C+Francois%3BLamoreux%2C+M+Lynn%3BHearing%2C+Vincent+J&rft.aulast=Costin&rft.aufirst=Gertrude-E&rft.date=2004-12-01&rft.volume=335&rft.issue=1&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Analytical+Biochemistry&rft.issn=00032697&rft_id=info:doi/10.1016%2Fj.ab.2004.07.035 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-09-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pigmentation; Mutation; Immortalization; Melanocytes DO - http://dx.doi.org/10.1016/j.ab.2004.07.035 ER - TY - JOUR T1 - Mesenchymal stem cell-based cartilage tissue engineering: cells, scaffold and biology AN - 19615247; 7347694 AB - Cartilage repair and regeneration by stem cell-based tissue engineering could be of enormous therapeutic and economic potential benefit for an aging population. However, to use stem cells effectively, their natural environment must be understood in order to expand them in vitro without compromising their multilineage potential and their specific differentiation program. Collaboration between diverse academic disciplines and between research and regulatory government agencies and industry is crucial before cell-based cartilage tissue engineering can achieve its full therapeutic potential. JF - Cytotherapy AU - Song, L AU - Baksh, D AU - Tuan, R S AD - Cartilage Biology and Orthopedics Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, Department and Health and Human Services, NIH, Bethesda, Maryland, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 596 EP - 601 PB - Taylor & Francis Ltd., 11 New Fetter Lane London EC4P 4EE UK, [mailto:info@tandf.co.uk], [URL:http://www.tandf.co.uk] VL - 6 IS - 6 SN - 1465-3249, 1465-3249 KW - Biotechnology and Bioengineering Abstracts; Calcium & Calcified Tissue Abstracts KW - Cartilage KW - Aging KW - Tissue engineering KW - scaffolds KW - Differentiation KW - Stem cells KW - Economics KW - Mesenchyme KW - T 2030:Cartilage and Cartilage Diseases KW - W 30920:Tissue Engineering UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19615247?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytotherapy&rft.atitle=Mesenchymal+stem+cell-based+cartilage+tissue+engineering%3A+cells%2C+scaffold+and+biology&rft.au=Song%2C+L%3BBaksh%2C+D%3BTuan%2C+R+S&rft.aulast=Song&rft.aufirst=L&rft.date=2004-12-01&rft.volume=6&rft.issue=6&rft.spage=596&rft.isbn=&rft.btitle=&rft.title=Cytotherapy&rft.issn=14653249&rft_id=info:doi/10.1080%2F14653240410005276 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-05-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tissue engineering; Cartilage; Economics; scaffolds; Differentiation; Aging; Mesenchyme; Stem cells DO - http://dx.doi.org/10.1080/14653240410005276 ER - TY - JOUR T1 - Case Report: Cysticercal chronic basal arachnoiditis with infarcts, mimicking tuberculous pathology in endemic areas AN - 19407356; 6225180 AB - Neurocysticercosis (NCC) is the most common of the parasitic diseases affecting the CNS, with protean clinical manifestations. Stroke as a complication of NCC occurs in a very small percentage of cases, mostly involving small perforating vessels while major intracranial vessel involvement is extremely rare. The present report involves two autopsied cases of chronic cysticercal basal arachnoiditis causing large arterial territory infarcts and, in the second case, a hypothalamic mass. They were diagnosed and managed, clinically and by neuroimaging, as stroke and neurotuberculosis, respectively. The diagnosis was established only at autopsy, which revealed NCC causing basal arachnoiditis, major vessel vasculitis and infarcts. Histologically, case 1 showed degenerating racemose cysticercal cyst within the thick basal exudate. In the second case, remnants of the degenerated cysticercal cyst in the form of hooklets and calcareous corpuscles were identified within the giant cell inciting a granulomatous response to form a hypothalamic mass lesion mimicking tuberculoma. The present case report highlights the importance of considering the non-tuberculous etiologies of chronic basal arachnoiditis like NCC before initiating therapy especially in countries endemic to both NCC and tuberculosis, like India. JF - Neuropathology AU - Aditya, Gopaliah Shivane AU - Mahadevan, Anita AU - Santosh, Vani AU - Chickabasaviah, Yasha Thagadur AU - Ashwathnarayanarao, Chandramouli Bangalore AU - Krishna, Shankar Susarla AD - Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India, shankar@nimhans.kar.nic.in Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 320 EP - 325 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 24 IS - 4 SN - 0919-6544, 0919-6544 KW - Microbiology Abstracts B: Bacteriology; CSA Neurosciences Abstracts KW - Giant cells KW - Central nervous system KW - Mimicry KW - Autopsy KW - Neuroimaging KW - Hypothalamus KW - Etiology KW - Vasculitis KW - Mycobacterium KW - cysticercosis KW - Stroke KW - Territory KW - Arachnoiditis KW - Cysts KW - Tuberculoma KW - Exudates KW - Case reports KW - Corpuscles KW - Cysticercosis KW - Tuberculosis KW - Parasitic diseases KW - Taenia KW - J 02400:Human Diseases KW - N3 11027:Neurology & neuropathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19407356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropathology&rft.atitle=Case+Report%3A+Cysticercal+chronic+basal+arachnoiditis+with+infarcts%2C+mimicking+tuberculous+pathology+in+endemic+areas&rft.au=Aditya%2C+Gopaliah+Shivane%3BMahadevan%2C+Anita%3BSantosh%2C+Vani%3BChickabasaviah%2C+Yasha+Thagadur%3BAshwathnarayanarao%2C+Chandramouli+Bangalore%3BKrishna%2C+Shankar+Susarla&rft.aulast=Aditya&rft.aufirst=Gopaliah&rft.date=2004-12-01&rft.volume=24&rft.issue=4&rft.spage=320&rft.isbn=&rft.btitle=&rft.title=Neuropathology&rft.issn=09196544&rft_id=info:doi/10.1111%2Fj.1440-1789.2004.00564.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-05-01 N1 - SuppNotes - Figures, 5; references, 13. N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Giant cells; Autopsy; Mimicry; Central nervous system; Etiology; Hypothalamus; Neuroimaging; Vasculitis; cysticercosis; Stroke; Territory; Arachnoiditis; Cysts; Tuberculoma; Exudates; Case reports; Corpuscles; Cysticercosis; Tuberculosis; Parasitic diseases; Mycobacterium; Taenia DO - http://dx.doi.org/10.1111/j.1440-1789.2004.00564.x ER - TY - JOUR T1 - Biologically active substances from amphibians: preliminary studies on anurans from twenty-one genera of Thailand AN - 19405167; 6094264 AB - Amphibian skin has been the source of a wide variety of biologically active substances, but less than one-third of the known genera of amphibians have been probed for such active substances. Skins of 21 genera of anurans from Thailand have now been investigated for noxious secretions, toxic substances, and alkaloids. Four genera of bufonid toads (Bufo, Ansonia, Leptophryne, Pedostipes) were toxic due to the presence of bufadienolides or bufadienolide- like compounds. Two species of ranid frogs (Rana raniceps, Rana signata) were toxic, perhaps due to the presence of toxic peptide(s). Two species of rhacophorid frogs (Polypedates) were slightly noxious/toxic. One species of microhylid frog (Kaloula pulchra) was noxious. Trace amounts of pumiliotoxin alkaloids were detected in a ranid frog (Limnonectes kuhli). A further 18 species did not exhibit noxious or toxic properties to a significant extent. JF - Toxicon AU - Daly, J W AU - Noimai, N AU - Kongkathip, B AU - Kongkathip, N AU - Wilham, J M AU - Garraffo, H M AU - Kaneko, T AU - Spande, T F AU - Nimit, Y AU - Nabhitabhata, J AU - Chan-Ard, T AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, DHHS, NIH, Bldg. 8, Rm. 1A17, Bethesda, MD 20892 USA, jdaly@nih.gov Y1 - 2004/12// PY - 2004 DA - December 2004 SP - 805 EP - 815 PB - Elsevier Science Ltd., Pergamon, P.O. Box 800 Kidlington Oxford OX5 1DX UK, [mailto:nlinfo-f@elsevier.nl] VL - 44 IS - 8 SN - 0041-0101, 0041-0101 KW - Amphibians KW - Frogs KW - Toads KW - True frogs KW - ASFA 1: Biological Sciences & Living Resources; Toxicology Abstracts KW - Toxicity KW - Bufadienolides KW - Pumiliotoxins KW - Serotonin KW - Skin KW - Amphibiotic species KW - Thailand KW - Secretion KW - Secretions KW - Anura KW - Kaloula pulchra KW - Rana KW - Animal physiology KW - Kaloula KW - Freshwater KW - Ansonia KW - Amphibia KW - Bufo KW - Polypedates KW - Alkaloids KW - Limnonectes kuhli KW - Limnonectes KW - Raniceps KW - Q1 08326:Physiology, biochemistry, biophysics KW - X 24173:Animals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19405167?accountid=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=Toxicon&rft.atitle=Biologically+active+substances+from+amphibians%3A+preliminary+studies+on+anurans+from+twenty-one+genera+of+Thailand&rft.au=Daly%2C+J+W%3BNoimai%2C+N%3BKongkathip%2C+B%3BKongkathip%2C+N%3BWilham%2C+J+M%3BGarraffo%2C+H+M%3BKaneko%2C+T%3BSpande%2C+T+F%3BNimit%2C+Y%3BNabhitabhata%2C+J%3BChan-Ard%2C+T&rft.aulast=Daly&rft.aufirst=J&rft.date=2004-12-01&rft.volume=44&rft.issue=8&rft.spage=805&rft.isbn=&rft.btitle=&rft.title=Toxicon&rft.issn=00410101&rft_id=info:doi/10.1016%2Fj.toxicon.2004.08.016 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-02-01 N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Alkaloids; Amphibiotic species; Secretion; Animal physiology; Skin; Secretions; Amphibia; Polypedates; Bufo; Limnonectes kuhli; Limnonectes; Kaloula pulchra; Anura; Rana; Kaloula; Ansonia; Raniceps; Thailand; Freshwater DO - http://dx.doi.org/10.1016/j.toxicon.2004.08.016 ER - TY - JOUR T1 - Cadmium at a non-toxic dose alters gene expression in mouse testes AN - 18066499; 6065280 AB - The testes are important targets of cadmium (Cd)-induced toxicity and carcinogenicity in rodents. Exposure to Cd at environmentally relevant low levels is a significant human health concern, but the effects of Cd on the rodent testes at doses that do not cause overt lesions are poorly defined. We used cDNA microarray and quantitative real-time RT-PCR assays to determine gene expression profiles in the testes of CD-1 mice 12-72 h after a single s.c. injection of 5 mu mol/kg CdCl sub(2). This dose of Cd did not produce overt histopathological changes, but clearly altered the expression of some genes that are likely to be important in toxicity responses. The most significant changes in gene expression occurred 24 h after treatment, corresponding to when the highest level of Cd was detected in the testes. Increased expression of the C-myc and Egr1 genes strongly suggests acute stress responses. Repressed expression of cell cycle-regulated cyclin B1 and CDC2 proteins indicates a potential for causing G2/M arrest and disturbance of meiosis. Decreased expression of pro-apoptotic genes, particularly Casp3, and DNA repair genes possibly contributes to Cd-induced carcinogenesis. These results indicate that changes in gene expression occur well before overt effects of Cd- induced testicular toxicity and carcinogenicity are apparent. JF - Toxicology Letters AU - Zhou, T AU - Jia, X AU - Chapin, R E AU - Maronpot, R R AU - Harris, M W AU - Liu, J AU - Waalkes, M P AU - Eddy, E M AD - Gamete Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA, eddy@niehs.nih.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 191 EP - 200 PB - Elsevier Science Ireland Ltd., Elsevier House, Brookvale Plaza East Park Shannon, Co. Clare Ireland, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 154 IS - 3 SN - 0378-4274, 0378-4274 KW - Toxicology Abstracts KW - Testes KW - EGR-1 gene KW - c-myc gene KW - Toxicity KW - DNA repair KW - DNA microarrays KW - Gene expression KW - Meiosis KW - Cyclin B1 KW - Carcinogenicity KW - Carcinogenesis KW - Polymerase chain reaction KW - Cadmium KW - Cdc2 protein KW - X 24165:Biochemistry KW - X 24162:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18066499?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Cadmium+at+a+non-toxic+dose+alters+gene+expression+in+mouse+testes&rft.au=Zhou%2C+T%3BJia%2C+X%3BChapin%2C+R+E%3BMaronpot%2C+R+R%3BHarris%2C+M+W%3BLiu%2C+J%3BWaalkes%2C+M+P%3BEddy%2C+E+M&rft.aulast=Belur&rft.aufirst=Jyoti&rft.date=2009-05-01&rft.volume=25&rft.issue=2&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Journal+of+Contemporary+Criminal+Justice&rft.issn=10439862&rft_id=info:doi/10.1177%2F1043986209333594 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Testes; Gene expression; Toxicity; Carcinogenicity; Cadmium; Cdc2 protein; EGR-1 gene; Cyclin B1; c-myc gene; DNA microarrays; Carcinogenesis; DNA repair; Meiosis; Polymerase chain reaction DO - http://dx.doi.org/10.1016/j.toxlet.2004.07.015 ER - TY - JOUR T1 - Mercury concentrations in brain and kidney following ethylmercury, methylmercury and Thimerosal administration to neonatal mice AN - 18062735; 6065283 AB - The distribution of mercury to the brain following an injection of methylmercury (MeHg) or ethylmercury (EtHg) was examined in immature mice. Postnatal day (PND) 16 CD1 mice received MeHg chloride either by IM injection or by gavage. At 24 h and 7 days post-injection, total mercury concentrations were determined in blood, kidney, brain, and muscle by cold vapor atomic fluorescence spectrometry. At 24 h, an IM injection of MeHg chloride (17.4 mu g) produced total mercury concentrations in the blood (6.2 plus or minus 0.9 mu g/g), brain (5.6 plus or minus 1.3 mu g; 0.6% delivered dose), and kidney (25.2 plus or minus 5.6 mu g; 1.1%), approximately 30% of that obtained from oral administration (blood: 17.9 plus or minus 1.0 mu g; brain: 16.1 plus or minus 1.2 mu g, 1.5%; kidney: 64.9 [plus-or-minus- sign] 6.3 mu g, 2.7%). For comparison, PND 16 mice received an IM injection of concentrated dosing suspensions (2 mu l dosing vol.) for EtHg chloride (6 mu g) or Thimerosal (15.4 mu g). For EtHg, approximately 0.39 [plus-or-minus- sign] 0.06% of the injected mercury was detected in the brain and 3.5 [plus-or- minus-sign] 0.6% in the kidney at 24 h. Thimerosal IM injection resulted in 0.22 plus or minus 0.04% in the brain, and 1.7 plus or minus 0.3% in the kidney. By 7 days, mercury levels decreased in the blood but were unchanged in the brain. An acute IM injection to adult mice of each suspension at a 10- fold higher dose resulted an average 0.1% mercury in the brain, and higher levels in the blood, kidney, and muscle as compared to the young. In immature mice, MeHg delivered via oral route of administration resulted in significantly greater tissue levels as compared to levels from IM injection. Comparisons of tissue distribution following IM administration suggest that an oral route of administration for mercury is not comparable to an IM delivery and that MeHg does not appear to be a good model for EtHg-containing compounds. JF - Toxicology Letters AU - Harry, G J AU - Harris, M W AU - Burka, L T AD - Laboratory of Neurobiology, Neurotoxicology Group, National Institute of Environmental Health Sciences, P.O. Box 12233, MD C1-04, Research Triangle Park, NC 27709, USA, harry@niesh.nih.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 183 EP - 189 PB - Elsevier Science Ireland Ltd., Elsevier House, Brookvale Plaza East Park Shannon, Co. Clare Ireland, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 154 IS - 3 SN - 0378-4274, 0378-4274 KW - ethylmercury chloride KW - ethylmercury KW - Toxicology Abstracts KW - thimerosal KW - Blood KW - Oral administration KW - Animal models KW - Dimethylmercury KW - Kidney KW - Mercury KW - Neonates KW - Spectrometry KW - X 24163:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18062735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Mercury+concentrations+in+brain+and+kidney+following+ethylmercury%2C+methylmercury+and+Thimerosal+administration+to+neonatal+mice&rft.au=Harry%2C+G+J%3BHarris%2C+M+W%3BBurka%2C+L+T&rft.aulast=Harry&rft.aufirst=G&rft.date=2004-12-01&rft.volume=154&rft.issue=3&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/10.1016%2Fj.toxlet.2004.07.014 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mercury; Kidney; Dimethylmercury; Blood; thimerosal; Neonates; Spectrometry; Animal models; Oral administration DO - http://dx.doi.org/10.1016/j.toxlet.2004.07.014 ER - TY - JOUR T1 - Ethosuximide and valproate display high efficacy against lindane-induced seizures in mice AN - 18060341; 6034980 AB - Both lindane ( gamma -hexachlorocyclohexane), an organochlorine ectoparasiticide and pentylenetetrazol, used as a model of experimental epilepsy, produce convulsive seizures resulting from the blockade of the gamma -aminobutyric acid (GABA sub(A)) receptor. In the present study we established the protective effects of ethosuximide and valproate against seizures induced by lindane and compared them with the well-known protective effects of these drugs against pentylenetetrazol-induced seizures in mice. Both ethosuximide and valproate afforded complete and dose-dependent protection against seizures induced by lindane. However, the potencies of these drugs were lower than those obtained against pentylenetetrazol seizures. Nevertheless, the protective efficacy of ethosuximide and valproate against experimentally induced lindane seizures may suggest possible efficacy of these drugs against seizures in lindane-poisoned patients. JF - Toxicology Letters AU - Kaminski, R M AU - Tochman, A M AU - Dekundy, A AU - Turski, WA AU - Czuczwar, S J AD - Isotope Laboratory, Institute of Agricultural Medicine, Jaczewskiego 8, 20- 950 Lublin, Poland, kaminskr@ninds.nih.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 55 EP - 60 PB - Elsevier Science Ireland Ltd., Elsevier House, Brookvale Plaza East Park Shannon, Co. Clare Ireland, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 154 IS - 1-2 SN - 0378-4274, 0378-4274 KW - mice KW - ethosuximide KW - Toxicology Abstracts KW - Organochlorine compounds KW - Pentylenetetrazole KW - Epilepsy KW - Valproic acid KW - Seizures KW - Animal models KW - ^g-Aminobutyric acid KW - Lindane KW - Drugs KW - X 24135:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18060341?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Ethosuximide+and+valproate+display+high+efficacy+against+lindane-induced+seizures+in+mice&rft.au=Kaminski%2C+R+M%3BTochman%2C+A+M%3BDekundy%2C+A%3BTurski%2C+WA%3BCzuczwar%2C+S+J&rft.aulast=Kaminski&rft.aufirst=R&rft.date=2004-12-01&rft.volume=154&rft.issue=1-2&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/10.1016%2Fj.toxlet.2004.07.002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Seizures; Lindane; Drugs; ^g-Aminobutyric acid; Valproic acid; Epilepsy; Animal models; Pentylenetetrazole; Organochlorine compounds DO - http://dx.doi.org/10.1016/j.toxlet.2004.07.002 ER - TY - JOUR T1 - Cancer Incidence Among Pesticide Applicators Exposed to Chlorpyrifos in the Agricultural Health Study AN - 17853625; 6099164 AB - BACKGROUND: Chlorpyrifos is one of the most widely used insecticides in the United States. We evaluated the incidence of cancer among pesticide applicators exposed to chlorpyrifos in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. METHODS: A total of 54 383 pesticide applicators were included in this analysis. Detailed information on pesticide exposure and lifestyle factors was obtained from self- administered questionnaires completed at the time of enrollment (December 1993- December 1997). Poisson regression analysis was used to evaluate the association between chlorpyrifos exposure and cancer incidence after adjustment for potential confounders. All statistical tests were two-sided. RESULTS: A total of 2070 incident malignant neoplasms were diagnosed through 2001. The rate ratio for all cancers combined among chlorpyrifos-exposed applicators compared with nonexposed applicators was 0.97 (95% confidence interval = 0.87 to 1.08). For most cancers analyzed, there was no evidence of an exposure-response relationship. However, the incidence of lung cancer was statistically significantly associated with both chlorpyrifos lifetime exposure-days (P sub(trend) = .002) and chlorpyrifos intensity-weighted exposure-days (P sub(trend) = .036). After adjustment for other pesticide exposures and demographic factors, individuals in the highest quartile of chlorpyrifos lifetime exposure-days (>56 days) had a relative risk of lung cancer 2.18 (95% confidence interval = 1.31 to 3.64) times that of those with no chlorpyrifos exposure. CONCLUSION: Our findings suggest an association between chlorpyrifos use and incidence of lung cancer that deserves further evaluation. JF - Journal of the National Cancer Institute AU - Lee, Won Jin AU - Blair, Aaron AU - Hoppin, Jane A AU - Lubin, Jay H AU - Rusiecki, Jennifer A AU - Sandler, Dale P AU - Dosemeci, Mustafa AU - Alavanja, Michael CR AD - Occupational and Environmental Epidemiology Branch, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD Y1 - 2004/12/01/ PY - 2004 DA - 2004 Dec 01 SP - 1781 EP - 1789 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 96 IS - 23 SN - 0027-8874, 0027-8874 KW - Risk Abstracts; Health & Safety Science Abstracts KW - USA, North Carolina KW - Chlorpyrifos KW - Insecticides KW - USA, Iowa KW - Occupational exposure KW - Lung cancer KW - R2 23080:Industrial and labor KW - H 5000:Pesticides UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17853625?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Cancer+Incidence+Among+Pesticide+Applicators+Exposed+to+Chlorpyrifos+in+the+Agricultural+Health+Study&rft.au=Lee%2C+Won+Jin%3BBlair%2C+Aaron%3BHoppin%2C+Jane+A%3BLubin%2C+Jay+H%3BRusiecki%2C+Jennifer+A%3BSandler%2C+Dale+P%3BDosemeci%2C+Mustafa%3BAlavanja%2C+Michael+CR&rft.aulast=Lee&rft.aufirst=Won&rft.date=2004-12-01&rft.volume=96&rft.issue=23&rft.spage=1781&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - USA, Iowa; USA, North Carolina; Insecticides; Lung cancer; Chlorpyrifos; Occupational exposure ER - TY - JOUR T1 - Contralateral Breast Cancer and Thromboembolic Events in African American Women Treated With Tamoxifen AN - 17851893; 6099162 AB - BACKGROUND: Information about breast cancer treatment and prevention in African American women is scant, and recommendations for therapy from clinical trials for breast cancer are based primarily on data obtained from white women. METHODS: We compared the effects of tamoxifen on risk of contralateral breast cancer and thromboembolic events in African American women and white women with a history of primary breast cancer. Data from 13 National Surgical Adjuvant Breast and Bowel Project clinical trials were pooled for analyses of time to contralateral breast cancer as a first event (eight trials and 10 619 patients) and of time to any thromboembolic phenomenon as a first event (all 13 trials and 20 878 patients). Risk factors for contralateral breast cancer and thromboembolic events among all women were determined using univariate proportional hazards models. (For each racial group, the rate of events associated with tamoxifen use was calculated as the ratio of the incidence rate with tamoxifen to that without tamoxifen.) Proportional hazards regression models were used to calculate 95% confidence intervals (CIs) and risk ratios. All statistical tests were two-sided. RESULTS: Risk factors for contralateral breast cancer were body mass index (BMI) and lymph node positivity; those for thromboembolic events were BMI and age. In women of both ethnicities with estrogen receptor-positive breast cancer, those who took tamoxifen experienced a similar reduction in contralateral breast cancer (risk ratio for African American women = 0.74, 95% CI = 0.46 to 1.17, n = 690; risk ratio for white women = 0.76, 95% CI = 0.59 to 0.98, n = 9929; P = .92). Tamoxifen was also associated with an increase in thromboembolic events. The relative risk for thromboembolic events was higher in both African American and white women treated with tamoxifen and chemotherapy than in those who were treated with tamoxifen alone (risk ratio for African American women = 10.70, 95% CI = 5.94 to 19.28 versus 2.16, 95% CI = 1.26 to 3.71; n = 1842; risk ratio for white women = 15.49, 95% CI = 9.53 to 25.17 versus 3.13, 95% CI = 2.04 to 4.79, n = 19 036), and this effect was similar between the races (P = .10). CONCLUSIONS: African American and white women appear to have the same risks of contralateral breast cancer and thromboembolic events in response to tamoxifen treatment. JF - Journal of the National Cancer Institute AU - Mccaskill-Stevens, Worta AU - Wilson, John AU - Bryant, John AU - Mamounas, Eleftherios AU - Garvey, Lori AU - James, Joan AU - Cronin, Walter AU - Wickerham, DLawrence AD - Division of Cancer Prevention, National Cancer Institute, Bethesda, MD (WMS) Y1 - 2004/12/01/ PY - 2004 DA - 2004 Dec 01 SP - 1762 EP - 1769 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 96 IS - 23 SN - 0027-8874, 0027-8874 KW - tamoxifen KW - Risk Abstracts; Health & Safety Science Abstracts KW - Thromboembolism KW - Breast cancer KW - Side effects KW - Ethnic groups 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/17851893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Contralateral+Breast+Cancer+and+Thromboembolic+Events+in+African+American+Women+Treated+With+Tamoxifen&rft.au=Mccaskill-Stevens%2C+Worta%3BWilson%2C+John%3BBryant%2C+John%3BMamounas%2C+Eleftherios%3BGarvey%2C+Lori%3BJames%2C+Joan%3BCronin%2C+Walter%3BWickerham%2C+DLawrence&rft.aulast=Mccaskill-Stevens&rft.aufirst=Worta&rft.date=2004-12-01&rft.volume=96&rft.issue=23&rft.spage=1762&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Ethnic groups; Breast cancer; Side effects; Thromboembolism ER - TY - JOUR T1 - Antisense radiotherapy: targeting full-size mdr1 mRNA with super(125)I-labelled oligonucleotides AN - 17834312; 6199091 AB - Purpose: Antisense radiotherapy is an approach based on the targeting of mRNA of specific genes by complementary oligonucleotide probes labelled with an Auger-electron-emitting radioisotope. Decay of the Auger emitter should specifically destroy the targeted mRNA while producing minimal damage to the rest of mRNA pool and the nuclear DNA. The feasibility of this approach was investigated by using full-length human multidrug-resistance gene (mdr1) mRNA as a target. Materials and methods: Antisense oligonucleotides were labelled with [ super(125)I] I-dCTP by primer extension and annealed to target mRNA. Breaks in the target mRNA were analysed by denaturing polyacrylamide gel electriphoresis. Results: The efficiency of super(125)I-labelled antisense oligonucleotides in producing RNA strand breaks was tested on short synthetic RNA and DNA targets. The position and specificity of super(125)I-induced breaks in the full-length mRNA were then tested and compared with the cleavage of the target by RNase H. The distribution of the breaks in the longer mRNA is different from that in the short RNA targets, most likely due to a complex folding of RNA strands in the full-length mRNA. Conclusions: The authors posit that super(125)I-labelled antisense probes could be useful not only for targeting mRNA, but also as probes for mRNA folding in vivo. JF - International Journal of Radiation Biology AU - Gaidamakova, E K AU - Neumann, R D AU - Panyutin, I G AD - Nuclear Medicine Department National Institutes of Health Bethesda MD 20892-1180 USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 889 EP - 893 VL - 80 IS - 11-12 SN - 0955-3002, 0955-3002 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Antisense oligonucleotides KW - MDR gene KW - DNA probes KW - Ribonuclease H KW - Radioisotopes KW - Radiotherapy KW - DNA breaks KW - mRNA KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17834312?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Radiation+Biology&rft.atitle=Antisense+radiotherapy%3A+targeting+full-size+mdr1+mRNA+with+super%28125%29I-labelled+oligonucleotides&rft.au=Gaidamakova%2C+E+K%3BNeumann%2C+R+D%3BPanyutin%2C+I+G&rft.aulast=Gaidamakova&rft.aufirst=E&rft.date=2004-12-01&rft.volume=80&rft.issue=11-12&rft.spage=889&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Biology&rft.issn=09553002&rft_id=info:doi/10.1080%2F09553000400007706 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - mRNA; MDR gene; DNA probes; DNA breaks; Antisense oligonucleotides; Radiotherapy; Ribonuclease H; Radioisotopes DO - http://dx.doi.org/10.1080/09553000400007706 ER - TY - JOUR T1 - Assessment of DNA damage produced by super(125)I-triplex-forming oligonucleotides in cells AN - 17832035; 6199093 AB - Purpose: Triplex-forming oligodeoxyribonucleotides (TFOs) bind specifically to their target sequences by forming hydrogen bonds within the major groove of the target duplex. When labeled with Auger-electron-emitting radioisotopes, TFOs are able to damage the target gene in a process named antigene radiotherapy. We compared radiotoxicity and the amount of DNA damage produced within cultured cells by two super(125)I-labeled TFOs, one with a single target in the genome and another with multiple targets. Materials and methods: Radiotoxicity was measured by clonogenic assay while DNA damage was assessed by the number of histone Y-H2AX foci formed at the sites of DNA double strand breaks (DSBs). Results: The TFO with multiple nuclear targets was 1.7 fold more radiotoxic and produced on average 1.9 fold more Y-H2AX foci per cell than the TFO with a single target. Conclusion: Since the two methods gave comparable results, measuring the number of Y-H2AX foci per decay may be a useful procedure for the assessment of cytotoxic effects and the intranuclear localization of radionuclides when they produce DSBs. JF - International Journal of Radiation Biology AU - Sedelnikova, O A AU - Panyutin, I V AU - Neumann, R D AU - Bonner, WM AU - Panyutin, I G AD - Laboratory of Molecular Pharmacology, CCR NCI, Department of Nuclear Medicine, Clinical Center NIH Bethesda MD 20892, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 927 EP - 931 VL - 80 IS - 11-12 SN - 0955-3002, 0955-3002 KW - Toxicology Abstracts KW - DNA damage KW - Cytotoxicity KW - Histones KW - Hydrogen bonding KW - Radioisotopes KW - Radiotherapy KW - Iodine KW - Decay KW - Oligonucleotides KW - X 24210:Radiation & radioactive materials KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17832035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Radiation+Biology&rft.atitle=Assessment+of+DNA+damage+produced+by+super%28125%29I-triplex-forming+oligonucleotides+in+cells&rft.au=Sedelnikova%2C+O+A%3BPanyutin%2C+I+V%3BNeumann%2C+R+D%3BBonner%2C+WM%3BPanyutin%2C+I+G&rft.aulast=Sedelnikova&rft.aufirst=O&rft.date=2004-12-01&rft.volume=80&rft.issue=11-12&rft.spage=927&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Biology&rft.issn=09553002&rft_id=info:doi/10.1080%2F09553000400017648 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA damage; Oligonucleotides; Radioisotopes; Hydrogen bonding; Histones; Decay; Iodine; Cytotoxicity; Radiotherapy DO - http://dx.doi.org/10.1080/09553000400017648 ER - TY - JOUR T1 - Analysis of Phenanthrols in Human Urine by Gas Chromatography-Mass Spectrometry: Potential Use in Carcinogen Metabolite Phenotyping AN - 17824601; 6115824 AB - Phenanthrene is the simplest polycyclic aromatic hydrocarbon (PAH) containing a bay region, a feature closely associated with carcinogenicity. We have proposed that measurement of phenanthrene metabolites in human urine could be used to identify interindividual differences in metabolic activation and detoxification of PAH, and that these differences may be related to cancer susceptibility in smokers and other exposed individuals. Previously, we reported a method for quantitation of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4- tetrahydrophenanthrene (trans, anti-PheT) in human urine. trans, anti-PheT is the ultimate product of the diol epoxide metabolic activation pathway of phenanthrene. In this study, we have extended our carcinogen metabolite phenotyping approach by developing a method for quantitation of phenanthrols in human urine. PAH phenols such as phenanthrols are considered as detoxification products. After treatment of the urine by beta-glucuronidase and arylsulfatase, a fraction enriched in phenanthrols was prepared by partitioning and solid phase extraction. The phenanthrols were silylated and analyzed by gas chromatography- positive ion chemical ionization-mass spectrometry with selected ion monitoring. [ring- super(13)C sub(6)]3-phenanthrol was used as an internal standard. Accurate and reproducible quantitation of four phenanthrols, 1-phenanthrol (1-HOPhe), 2- HOPhe, 3-HOPhe, and 4-HOPhe, was readily achieved. In smokers, mean levels of 1- HOPhe (0.96 +/-1.2 pmol/mg creatinine) and 3-HOPhe (0.82 +/-0.62 pmol/mg creatinine) were greater than those of 2-HOPhe (0.47 +/-0.29 pmol/mg creatinine), and 4-HOPhe (0.11 +/-0.07 pmol/mg creatinine). There were no significant differences between the levels of any of the phenanthrols in smokers and nonsmokers. Total levels of the quantified phenanthrols were highly correlated with those of 3-HOPhe. Ratios of phenanthrene metabolites representing activation and detoxification were calculated as trans, anti-PheT divided by 3-HOPhe. There was a 7.5-fold spread of ratios in smokers, and a 12.3-fold spread in nonsmokers, suggesting that this may be a useful parameter for distinguishing individual metabolic responses to PAH exposure. JF - Cancer Epidemiology, Biomarkers & Prevention AU - Carmella, Steven G AU - Chen, Menglan AU - Yagi, Haruhiko AU - Jerina, Donald M AU - Hecht, Stephen S AD - The Cancer Center, University of Minnesota, Minneapolis, Minnesota and Department of Health and Human Services, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 2167 EP - 2174 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 13 IS - 12 SN - 1055-9965, 1055-9965 KW - Toxicology Abstracts KW - Cerebroside-sulfatase KW - Polycyclic aromatic hydrocarbons KW - Epoxides KW - Carcinogens KW - Cancer KW - Phenols KW - Mass spectroscopy KW - Phenanthrene KW - Creatinine KW - Gas chromatography KW - Carcinogenicity KW - Urine KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17824601?accountid=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+Epidemiology%2C+Biomarkers+%26+Prevention&rft.atitle=Analysis+of+Phenanthrols+in+Human+Urine+by+Gas+Chromatography-Mass+Spectrometry%3A+Potential+Use+in+Carcinogen+Metabolite+Phenotyping&rft.au=Carmella%2C+Steven+G%3BChen%2C+Menglan%3BYagi%2C+Haruhiko%3BJerina%2C+Donald+M%3BHecht%2C+Stephen+S&rft.aulast=Carmella&rft.aufirst=Steven&rft.date=2004-12-01&rft.volume=13&rft.issue=12&rft.spage=2167&rft.isbn=&rft.btitle=&rft.title=Cancer+Epidemiology%2C+Biomarkers+%26+Prevention&rft.issn=10559965&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 - Urine; Creatinine; Phenanthrene; Carcinogens; Epoxides; Carcinogenicity; Cerebroside-sulfatase; Gas chromatography; Mass spectroscopy; Phenols; Cancer; Polycyclic aromatic hydrocarbons ER - TY - JOUR T1 - Three-dimensional Model of the Pore Form of Anthrax Protective Antigen. Structure and Biological Implications AN - 17822737; 6121742 AB - Although pore formation by protective antigen (PA) is critical to cell intoxication by anthrax toxin (AT), the structure of the pore form of PA (the PA63 pore) has not been determined. Hence, in this study, the PA63 pore was modeled using the X-ray structures of monomeric PA and heptameric alpha -hemolysin ( alpha -HL) as templates. The PA63 pore model consists of two weakly associated domains, namely the cap and stem domains. The ring-like cap domain has a length of 80 AA and an outside diameter of 120 AA, while the cylinder-like stem domain has a length of 100 AA and outside diameter of similar to 28 AA. This provides the PA63 pore model with a length of 180 AA. Based on experimental results, the channel in the PA63 pore model was built to have a minimum diameter of similar to 12 AA, depending on side chain conformations. Because of its large size and structural complexity, the all-atom model of the PA63 pore is the end-stage construction of four separate modeling projects described herein. The final model is consistent with published experimental results, including mutational analysis and channel conductance experiments. In addition, the model was energetically and hydropathically refined to optimize molecular packing within the protomers and at the protomer-protomer interfaces. By providing atomic detail to biochemical and biophysical data, the PA63 pore model may afford new insights into the binding mode of PA on the membrane surface, the prepore-pore transition, and the mechanism of cell entry by anthrax toxin. JF - Journal of Biomolecular Structure and Dynamics AU - Nguyen, T L AD - Developmental Therapeutics, Program, National Cancer Institute, 378 Ware Drive, Frederick MD 21702, USA, nguyent@ncifcrf.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 253 EP - 266 VL - 22 IS - 3 SN - 0739-1102, 0739-1102 KW - Toxicology Abstracts KW - Intoxication KW - Molecular modelling KW - Channel pores KW - Conductance KW - protective antigen KW - Crystal structure KW - Anthrax KW - Bacillus anthracis KW - Toxins KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17822737?accountid=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+Biomolecular+Structure+and+Dynamics&rft.atitle=Three-dimensional+Model+of+the+Pore+Form+of+Anthrax+Protective+Antigen.+Structure+and+Biological+Implications&rft.au=Nguyen%2C+T+L&rft.aulast=Nguyen&rft.aufirst=T&rft.date=2004-12-01&rft.volume=22&rft.issue=3&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+Structure+and+Dynamics&rft.issn=07391102&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Intoxication; Molecular modelling; Conductance; Channel pores; protective antigen; Crystal structure; Anthrax; Toxins; Bacillus anthracis ER - TY - JOUR T1 - Alcohol and road traffic injuries in South Asia: Challenges for prevention AN - 17781376; 6193420 AB - Among the one million people killed on the roads during 2000, nearly 75% died in developing countries of the world, about half of them in Asia. A selective examination of RTIs in the region indicate that they constitute the second or third leading cause of death in the 5-44 years age group. The increase in direct and indirect health risk associated with alcohol usage has been well-documented in recent years. Alcohol is a major risk factor for RTIs as it impairs judgment and increases the possibility of involvement in other high risk behaviours (e.g., speeding, violating traffic rules, etc.). Precise information on the involvement of alcohol in RTIs and deaths is clearly not available from South Asian countries. With the recognition that road safety needs to focus on reducing drinking and driving, many high-income countries have formulated and implemented a number of coordinated, integrated and sustainable programmes based on scientific research. Considering the gravity of the situation, ongoing efforts to reduce the problem and lessons learnt from high-income countries, it is important to change strategies and mechanisms to reduce drink driving in South Asia. JF - Journal of the College of Physicians and Surgeons, Pakistan AU - Gururaj, G AD - National Institute of Mental Health and Neuro Sciences; Bangalore-560029, India, guru@nimhans.kar.nic.in Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 713 EP - 718 VL - 14 IS - 12 SN - 1022-386X, 1022-386X KW - Risk Abstracts; Health & Safety Science Abstracts KW - Injuries KW - Motor vehicles KW - Accidents KW - prevention KW - Asia KW - Highways KW - Pakistan KW - Developing countries KW - Age KW - driving ability KW - traffic safety KW - Mortality KW - Alcohol 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/17781376?accountid=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+Criminal+Justice&rft.atitle=Police+officers%27+perceptions+of+the+Nigeria+police+force%3A+Its+effects+on+the+social+organization+of+policing&rft.au=Okereke%2C+Godpower+O.&rft.aulast=Okereke&rft.aufirst=Godpower&rft.date=1995-01-01&rft.volume=23&rft.issue=3&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Journal+of+Criminal+Justice&rft.issn=00472352&rft_id=info:doi/10.1016%2F0047-2352%2895%2900014-H LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Asia; Pakistan; Alcohol; Mortality; Highways; driving ability; prevention; Age; traffic safety; Developing countries; Injuries; Accidents; Motor vehicles ER - TY - JOUR T1 - Evaluation of the Role of Constitutive Isocitrate Lyase Activity in Yersinia pestis Infection of the Flea Vector and Mammalian Host AN - 17761720; 6093192 AB - Yersinia pestis, unlike the closely related Yersinia pseudotuberculosis, constitutively produces isocitrate lyase (ICL). Here we show that the Y. pestis aceA homologue encodes ICL and is required for growth on acetate but not for flea infection or virulence in mice. Thus, deregulation of the glyoxylate pathway does not underlie the recent adaptation of Y. pestis to arthropod-borne transmission. JF - Infection and Immunity AU - Sebbane, Florent AU - Jarrett, Clayton O AU - Linkenhoker, Jan R AU - Hinnebusch, BJoseph AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 7334 EP - 7337 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 72 IS - 12 SN - 0019-9567, 0019-9567 KW - Fleas KW - Microbiology Abstracts B: Bacteriology KW - Virulence KW - Adaptations KW - Siphonaptera KW - Isocitrate lyase KW - Vectors KW - Yersinia pseudotuberculosis KW - Yersinia pestis KW - Pseudotuberculosis KW - Acetic acid KW - Disease transmission KW - J 02870:Invertebrate bacteriology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17761720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evaluation+of+the+Role+of+Constitutive+Isocitrate+Lyase+Activity+in+Yersinia+pestis+Infection+of+the+Flea+Vector+and+Mammalian+Host&rft.au=Sebbane%2C+Florent%3BJarrett%2C+Clayton+O%3BLinkenhoker%2C+Jan+R%3BHinnebusch%2C+BJoseph&rft.aulast=Sebbane&rft.aufirst=Florent&rft.date=2004-12-01&rft.volume=72&rft.issue=12&rft.spage=7334&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Yersinia pestis; Yersinia pseudotuberculosis; Siphonaptera; Isocitrate lyase; Vectors; Acetic acid; Virulence; Adaptations; Disease transmission; Pseudotuberculosis ER - TY - JOUR T1 - Phenotypic Profiles of Enterotoxigenic Escherichia coli Associated with Early Childhood Diarrhea in Rural Egypt AN - 17759271; 6098776 AB - Enterotoxigenic Escherichia coli (ETEC) causes substantial diarrheal morbidity and mortality in young children in countries with limited resources. We determined the phenotypic profiles of 915 ETEC diarrheal isolates derived from Egyptian children under 3 years of age who participated in a 3-year population-based study. For each strain, we ascertained enterotoxin and colonization factor (CF) expression, the O:H serotype, and antimicrobial susceptibility. Sixty-one percent of the strains expressed heat-stable enterotoxin (ST) only, 26% expressed heat-labile enterotoxin (LT) alone, and 12% expressed both toxins. The most common CF phenotypes were colonization factor antigen I (CFA/I) (10%), coli surface antigen 6 (CS6) (9%), CS14 (6%), and CS1 plus CS3 (4%). Fifty-nine percent of the strains did not express any of the 12 CFs included in our test panel. Resistance of ETEC strains to ampicillin (63%), trimethoprim-sulfamethoxazole (52%), and tetracycline (43%) was common, while resistance to quinolone antibiotics was rarely detected. As for the distribution of observed serotypes, there was an unusually wide diversity of O antigens and H types represented among the 915 ETEC strains. The most commonly recognized composite ETEC phenotypes were ST CS14 O78:H18 (4%), ST (or LTST) CFA/I O128:H12 (3%), ST CS1+CS3 O6:H16 (2%), and ST CFA/I O153:H45 (1.5%). Temporal plots of diarrheal episodes associated with ETEC strains bearing common composite phenotypes were consistent with discrete community outbreaks either within a single or over successive warm seasons. These data suggest that a proportion of the disease that is endemic to young children in rural Egypt represents the confluence of small epidemics by clonally related ETEC strains that are transiently introduced or that persist in a community reservoir. JF - Journal of Clinical Microbiology AU - Shaheen, Hind I AU - Khalil, Sami B AU - Rao, Malla R AU - Abu Elyazeed, Remon AU - Wierzba, Thomas F AU - Peruski, Leonard F AU - Putnam, Shannon AU - Navarro, Armando AU - Morsy, Badria Z AU - Cravioto, Alejandro AU - Clemens, John D AU - Svennerholm, Ann-Mari AU - Savarino, Stephen J AD - U.S. Naval Medical Research Unit Number 3, Cairo. Egyptian Ministry of Health and Population, Abu Homos, Beheira Governorate, Egypt. U.S. Naval Medical Research Center, Silver Spring. Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, Bethesda, Maryland. National Autonomous University, Mexico City, Mexico Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 5588 EP - 5595 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 42 IS - 12 SN - 0095-1137, 0095-1137 KW - Microbiology Abstracts B: Bacteriology KW - Diarrhea KW - Serotypes KW - Escherichia coli KW - trimethoprim-sulfamethoxazole KW - Enterotoxins KW - Tetracyclines KW - Children KW - Toxins KW - Colonization factor KW - J 02710:Identification, taxonomy and typing KW - J 02823:In vitro and in vivo effects KW - J 02846:Gastrointestinal tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17759271?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Police+Quarterly&rft.atitle=Conducted+energy+device+use+in+municipal+policing%3A+Results+of+a+national+survey+on+policy+and+effectiveness+assessments&rft.au=Thomas%2C+Kyle+J.%3BCollins%2C+Peter+A.%3BLovrich%2C+Nicholas+P.&rft.aulast=Thomas&rft.aufirst=Kyle&rft.date=2010-09-01&rft.volume=13&rft.issue=3&rft.spage=290&rft.isbn=&rft.btitle=&rft.title=Police+Quarterly&rft.issn=10986111&rft_id=info:doi/10.1177%2F1098611110373995 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Children; Enterotoxins; Colonization factor; Serotypes; Tetracyclines; trimethoprim-sulfamethoxazole; Diarrhea; Toxins ER - TY - JOUR T1 - CXCR4-Transgene Expression Significantly Improves Marrow Engraftment of Cultured Hematopoietic Stem Cells AN - 17757442; 6099754 AB - Hematopoietic stem cells (HSCs) lose marrow reconstitution potential during ex vivo culture. HSC migration to stromal cell-derived factor (SDF)-1 (CXCL12) correlates with CXC chemokine receptor 4 (CXCR4) expression and marrow engraftment. We demonstrate that mobilized human CD34 super(+) peripheral blood stem cells (CD34 super(+) PBSCs) lose CXCR4 expression during prolonged culture. We transduced CD34 super(+) PBSCs with retrovirus vector encoding human CXCR4 and achieved 18-fold more CXCR4 expression in over 87% of CD34 super(+) cells. CXCR4- transduced cells yielded increased calcium flux and up to a 10-fold increase in migration to SDF-1. Six-day cultured CXCR4-transduced cells demonstrated significant engraftment in nonobese diabetic/severe combined immunodeficient mice under conditions in which control transduced cells resulted in low or no engraftment. We conclude that transduction-mediated overexpression of CXCR4 significantly improves marrow engraftment of cultured PBSCs. JF - Stem Cells AU - Brenner, Sebastian AU - Whiting-Theobald, Narda AU - Kawai, Toshinao AU - Linton, Gilda F AU - Rudikoff, Andrew G AU - Choi, Uimook AU - Ryser, Martin F AU - Murphy, Philip M AU - Sechler, Joan MG AU - Malech, Harry L AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 1128 EP - 1133 VL - 22 IS - 7 SN - 1066-5099, 1066-5099 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Bioengineering Abstracts KW - SDF-1 protein KW - CXC chemokine receptors KW - CXCR4 protein KW - Cell culture KW - Diabetes mellitus KW - Expression vectors KW - Stem cells KW - Retrovirus KW - Hemopoiesis KW - Cell migration KW - CXCL12 protein KW - W 30965:Miscellaneous, Reviews KW - W4 120:Genetic Engineering in Medicine KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17757442?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+Cells&rft.atitle=CXCR4-Transgene+Expression+Significantly+Improves+Marrow+Engraftment+of+Cultured+Hematopoietic+Stem+Cells&rft.au=Brenner%2C+Sebastian%3BWhiting-Theobald%2C+Narda%3BKawai%2C+Toshinao%3BLinton%2C+Gilda+F%3BRudikoff%2C+Andrew+G%3BChoi%2C+Uimook%3BRyser%2C+Martin+F%3BMurphy%2C+Philip+M%3BSechler%2C+Joan+MG%3BMalech%2C+Harry+L&rft.aulast=Brenner&rft.aufirst=Sebastian&rft.date=2004-12-01&rft.volume=22&rft.issue=7&rft.spage=1128&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&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 - CXCR4 protein; Stem cells; Cell migration; Cell culture; Hemopoiesis; CXCL12 protein; CXC chemokine receptors; Expression vectors; Diabetes mellitus; Retrovirus; SDF-1 protein ER - TY - JOUR T1 - Epitope Determinants of a Chimpanzee Fab Antibody That Efficiently Cross- Neutralizes Dengue Type 1 and Type 2 Viruses Map to Inside and in Close Proximity to Fusion Loop of the Dengue Type 2 Virus Envelope Glycoprotein AN - 17737595; 6079082 AB - The epitope determinants of chimpanzee Fab antibody 1A5, which have been shown to be broadly reactive to flaviviruses and efficient for cross- neutralization of dengue virus type 1 and type 2 (DENV-1 and DENV-2), were studied by analysis of DENV-2 antigenic variants. Sequence analysis showed that one antigenic variant contained a Gly-to-Val substitution at position 106 within the flavivirus-conserved fusion peptide loop of the envelope protein (E), and another variant contained a His-to-Gln substitution at position 317 in E. Substitution of Gly sub(106)Val in DENV-2 E reduced the binding affinity of Fab 1A5 by approximately 80-fold, whereas substitution of His sub(317)Gln had little or no effect on antibody binding compared to the parental virus. Treatment of DENV-2 with beta-mercaptoethanol abolished binding of Fab 1A5, indicating that disulfide bridges were required for the structural integrity of the Fab 1A5 epitope. Binding of Fab 1A5 to DENV-2 was competed by an oligopeptide containing the fusion peptide sequence as shown by competition enzyme-linked immunosorbent assay. Both DENV-2 antigenic variants were shown to be attenuated, or at least similar to the parental virus, when evaluated for growth in cultured cells or for neurovirulence in mice. Fab 1A5 inhibited low pH-induced membrane fusion of mosquito C6/36 cells infected with DENV-1 or DENV-2, as detected by reduced syncytium formation. Both substitutions in DENV-2 E lowered the pH threshold for membrane fusion, as measured in a fusion-from-within assay. In the three- dimensional structure of E, Gly sub(106) in domain II and His sub(317) in domain III of the opposite E monomer were spatially close. From the locations of these amino acids, Fab 1A5 appears to recognize a novel epitope that has not been mapped before with a flavivirus monoclonal antibody. JF - Journal of Virology AU - Goncalvez, Ana P AU - Purcell, Robert H AU - Lai, Ching-Juh AD - Molecular Viral Biology Section. Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Y1 - 2004/12/01/ PY - 2004 DA - 2004 Dec 01 SP - 12919 EP - 12928 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 78 IS - 23 SN - 0022-538X, 0022-538X KW - Chimpanzee KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Antigenic variants KW - Flavivirus KW - Envelopes KW - Dengue KW - Envelope protein KW - Glycoproteins KW - Dengue virus type 1 KW - Dengue virus type 2 KW - Epitopes KW - Enzyme-linked immunosorbent assay KW - Membrane fusion KW - Monoclonal antibodies KW - Neurovirulence KW - Pan troglodytes KW - Immunization (passive) KW - Fab KW - F 06002:Viruses KW - W3 33160:Antibody based KW - V 22093:Antigen-antibody interaction KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17737595?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Epitope+Determinants+of+a+Chimpanzee+Fab+Antibody+That+Efficiently+Cross-+Neutralizes+Dengue+Type+1+and+Type+2+Viruses+Map+to+Inside+and+in+Close+Proximity+to+Fusion+Loop+of+the+Dengue+Type+2+Virus+Envelope+Glycoprotein&rft.au=Goncalvez%2C+Ana+P%3BPurcell%2C+Robert+H%3BLai%2C+Ching-Juh&rft.aulast=Goncalvez&rft.aufirst=Ana&rft.date=2004-12-01&rft.volume=78&rft.issue=23&rft.spage=12919&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dengue virus type 1; Dengue virus type 2; Flavivirus; Pan troglodytes; Monoclonal antibodies; Fab; Glycoproteins; Envelopes; Enzyme-linked immunosorbent assay; Immunization (passive); Epitopes; Antigenic variants; Membrane fusion; Envelope protein; Neurovirulence; Dengue ER - TY - JOUR T1 - Chimpanzee Fab Fragments and a Derived Humanized Immunoglobulin G1 Antibody That Efficiently Cross-Neutralize Dengue Type 1 and Type 2 Viruses AN - 17732666; 6079081 AB - Passive immunization with monoclonal antibodies from humans or nonhuman primates represents an attractive alternative to vaccines for prevention of illness caused by dengue viruses (DENV) and other flaviviruses, including the West Nile virus. In a previous study, repertoire cloning to recover Fab fragments from bone marrow mRNA of chimpanzees infected with all four DENV serotypes (dengue virus serotype 1 [DENV-1] to DENV-4) was described. In that study, a humanized immunoglobulin G1 (IgG1) antibody that efficiently neutralized DENV-4 was recovered and characterized. In this study, the phage library constructed from the chimpanzees was used to recover Fab antibodies against the other three DENV serotypes. Serotype-specific neutralizing Fabs were not identified. Instead, we recovered DENV-neutralizing Fabs that specifically precipitated the envelope protein and were cross-reactive with all four DENV serotypes. Three of the Fabs competed with each other for binding to DENV-1 and DENV-2, although each of these Fabs contained a distinct complementarity determining region 3 (CDR3)-H sequence. Fabs that shared an identical or nearly identical CDR3-H sequences cross-neutralized DENV-1 and DENV-2 at a similar high 50% plaque reduction neutralization test (PRNT sub(50)) titer, ranging from 0.26 to 1.33 mu g/ml, and neutralized DENV-3 and DENV-4 but at a titer 10- to 20- fold lower. One of these Fabs, 1A5, also neutralized the West Nile virus most efficiently among other flaviviruses tested. Fab 1A5 was converted to a full- length antibody in combination with human sequences for production in mammalian CHO cells. Humanized IgG1 1A5 proved to be as efficient as Fab 1A5 for cross- neutralization of DENV-1 and DENV-2 at a titer of 0.48 and 0.95 mu g/ml, respectively. IgG1 1A5 also neutralized DENV-3, DENV-4, and the West Nile virus at a PRNT sub(50) titer of approximately 3.2 to 4.2 mu g/ml. This humanized antibody represents an attractive candidate for further development of immunoprophylaxis against DENV and perhaps other flavivirus-associated diseases. JF - Journal of Virology AU - Goncalvez, Ana P AU - Men, Ruhe AU - Wernly, Claire AU - Purcell, Robert H AU - Lai, Ching-Juh AD - Molecular Viral Biology Section. Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Y1 - 2004/12/01/ PY - 2004 DA - 2004 Dec 01 SP - 12910 EP - 12918 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 78 IS - 23 SN - 0022-538X, 0022-538X KW - Chimpanzee KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Dengue virus KW - Serotypes KW - Immunoprophylaxis KW - Bone marrow KW - Immunoglobulin G1 KW - Dengue KW - Envelope protein KW - Dengue virus type 1 KW - Dengue virus type 2 KW - Monoclonal antibodies KW - Primates KW - Pan troglodytes KW - Immunoglobulin G KW - Immunization (passive) KW - Fab KW - West Nile virus KW - W3 33160:Antibody based KW - F 06806:Passive immunization KW - V 22093:Antigen-antibody interaction KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17732666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chimpanzee+Fab+Fragments+and+a+Derived+Humanized+Immunoglobulin+G1+Antibody+That+Efficiently+Cross-Neutralize+Dengue+Type+1+and+Type+2+Viruses&rft.au=Goncalvez%2C+Ana+P%3BMen%2C+Ruhe%3BWernly%2C+Claire%3BPurcell%2C+Robert+H%3BLai%2C+Ching-Juh&rft.aulast=Goncalvez&rft.aufirst=Ana&rft.date=2004-12-01&rft.volume=78&rft.issue=23&rft.spage=12910&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - West Nile virus; Dengue virus; Primates; Dengue virus type 1; Dengue virus type 2; Pan troglodytes; Immunization (passive); Monoclonal antibodies; Fab; Immunoglobulin G; Serotypes; Dengue; Immunoglobulin G1; Bone marrow; Envelope protein; Immunoprophylaxis ER - TY - JOUR T1 - Recombinant Human Metapneumovirus Lacking the Small Hydrophobic SH and/or Attachment G Glycoprotein: Deletion of G Yields a Promising Vaccine Candidate AN - 17732179; 6079078 AB - Human metapneumovirus (HMPV) has recently been identified as a significant cause of serious respiratory tract disease in humans. In particular, the emerging information on the contribution of HMPV to pediatric respiratory tract disease suggests that it will be important to develop a vaccine against this virus for use in conjunction with those being developed for human respiratory syncytial virus and the human parainfluenza viruses. A recently described reverse genetic system (S. Biacchesi, M. H. Skiadopoulos, K. C. Tran, B. R. Murphy, P. L. Collins, and U. J. Buchholz, Virology 321:247-259, 2004) was used to generate recombinant HMPVs (rHMPVs) that lack the G gene, the SH gene, or both. The delta SH, delta G, and delta SH/G deletion mutants were readily recovered and were found to replicate efficiently during multicycle growth in cell culture. Thus, the SH and G proteins are not essential for growth in cell culture. Apart from the absence of the deleted protein(s), the virions produced by the gene deletion mutants were similar by protein yield and gel electrophoresis protein profile to wild-type HMPV. When administered intranasally to hamsters, the delta G and delta SH/G mutants replicated in both the upper and lower respiratory tracts, showing that HMPV containing F as the sole viral surface protein is competent for replication in vivo. However, both viruses were at least 40-fold and 600-fold restricted in replication in the lower and upper respiratory tract, respectively, compared to wild-type rHMPV. They also induced high titers of HMPV-neutralizing serum antibodies and conferred complete protection against replication of wild-type HMPV challenge virus in the lungs. Surprisingly, G is dispensable for protection, and the delta G and delta SH/G viruses represent promising vaccine candidates. In contrast, delta SH replicated somewhat more efficiently in hamster lungs compared to wild-type rHMPV (20-fold increase on day 5 postinfection). This indicates that SH is completely dispensable in vivo and that its deletion does not confer an attenuating effect, at least in this rodent model. JF - Journal of Virology AU - Biacchesi, Stephane AU - Skiadopoulos, Mario H AU - Yang, Lijuan AU - Lamirande, Elaine W AU - Tran, Kim C AU - Murphy, Brian R AU - Collins, Peter L AU - Buchholz, Ursula J AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland Y1 - 2004/12/01/ PY - 2004 DA - 2004 Dec 01 SP - 12877 EP - 12887 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 78 IS - 23 SN - 0022-538X, 0022-538X KW - man KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Virions KW - Replication KW - Pediatrics KW - Cell culture KW - Human respiratory syncytial virus KW - Gel electrophoresis KW - Parainfluenza KW - human parainfluenza virus KW - Respiratory tract diseases KW - Gene deletion KW - Lung KW - Human metapneumovirus KW - Glycoproteins KW - Vaccines KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17732179?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Recombinant+Human+Metapneumovirus+Lacking+the+Small+Hydrophobic+SH+and%2For+Attachment+G+Glycoprotein%3A+Deletion+of+G+Yields+a+Promising+Vaccine+Candidate&rft.au=Biacchesi%2C+Stephane%3BSkiadopoulos%2C+Mario+H%3BYang%2C+Lijuan%3BLamirande%2C+Elaine+W%3BTran%2C+Kim+C%3BMurphy%2C+Brian+R%3BCollins%2C+Peter+L%3BBuchholz%2C+Ursula+J&rft.aulast=Biacchesi&rft.aufirst=Stephane&rft.date=2004-12-01&rft.volume=78&rft.issue=23&rft.spage=12877&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 revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human respiratory syncytial virus; Human metapneumovirus; human parainfluenza virus; Vaccines; Respiratory tract diseases; Pediatrics; Replication; Cell culture; Lung; Gene deletion; Parainfluenza; Glycoproteins; Virions; Gel electrophoresis ER - TY - JOUR T1 - Ultraviolet light selection assay to optimize oligonucleotide correction of mutations in endogenous xeroderma pigmentosum genes AN - 17731960; 6091530 AB - Various oligonucleotide (ODN)-based approaches have been proposed for their ability to correct mutated genes at the normal chromosomal locations. However, the reported gene correction frequencies of these approaches have varied markedly in different experimental settings, including when different tissues or cell types are targeted. In order to find the optimal ODN-based approach for a specific target tissue, an assay system that allows direct comparison of the different methods on that tissue is necessary. Herein, we describe an XP-UVC selection assay that can be used to evaluate and compare gene correction frequencies in different cell types obtained from a xeroderma pigmentosum (XP) patient, following treatment by different ODN-based approaches. As an experimental example, the XP-UVC selection assay was used to assess the ability of chimeric RNA/DNA ODN to correct point mutations in the XPA gene. This assay can be used to assess and evaluate other types of ODN-based approaches, and to further optimize them. JF - Gene Therapy AU - Terunuma, A AU - Ye, J AU - Emmert, S AU - Khan, S G AU - Kraemer, KH AU - Vogel, J C AD - National Cancer Institute, Dermatology Branch, 10 Center Drive, MSC 1908, Building 10/Room 12N260, Bethesda, MD 20892-1908, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 1729 EP - 1734 VL - 11 IS - 23 SN - 0969-7128, 0969-7128 KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - X chromosome KW - Oligonucleotides KW - Chromosomes KW - U.V. radiation KW - Gene therapy KW - Point mutation KW - Light effects KW - Skin diseases KW - RNA KW - DNA KW - Xeroderma pigmentosum KW - W 30965:Miscellaneous, Reviews KW - N 14055:Techniques - Artificial, transgenic, antisense, other 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/17731960?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Ultraviolet+light+selection+assay+to+optimize+oligonucleotide+correction+of+mutations+in+endogenous+xeroderma+pigmentosum+genes&rft.au=Terunuma%2C+A%3BYe%2C+J%3BEmmert%2C+S%3BKhan%2C+S+G%3BKraemer%2C+KH%3BVogel%2C+J+C&rft.aulast=Terunuma&rft.aufirst=A&rft.date=2004-12-01&rft.volume=11&rft.issue=23&rft.spage=1729&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/10.1038%2Fsj.gt.3302344 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Oligonucleotides; Xeroderma pigmentosum; U.V. radiation; RNA; Gene therapy; X chromosome; Point mutation; Light effects; Skin diseases; Chromosomes; DNA DO - http://dx.doi.org/10.1038/sj.gt.3302344 ER - TY - JOUR T1 - A new harvest of fluorescent proteins AN - 17717503; 6133424 AB - In this issue, Shaner et al. describe a veritable cornucopia of new fluorescent proteins, including mCherry, mBanana, mOrange, mStrawberry, mTangerine and mHoneydew. Fluorescent proteins make possible the relatively straightforward study of favorite proteins within living cells, and cell biologists have become increasingly dependent on them as research tools. Why should this latest crop interest the average cell biologist? The limitations of existing fluorescent proteins have direct consequences for experimental design and interpretation. Shaner et al. address some of these drawbacks and present new variants that should extend our capabilities. JF - Nature Biotechnology AU - Patterson, George H AD - Cell Biology and Metabolism Branch of the National Institutes of Health, Bldg. 18T Rm. 101, 18 Library Drive, Bethesda, Maryland 20892-5430, USA, pattersg@mail.nih.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 1524 EP - 1525 PB - Nature Publishing Group VL - 22 IS - 12 SN - 1087-0156, 1087-0156 KW - orange fluorescent protein KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - Fluorescence KW - directed evolution KW - yellow fluorescent protein KW - red fluorescent protein KW - Reviews KW - Protein interaction KW - Discosoma KW - Color KW - W2 32340:Other peptides, proteins, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17717503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=A+new+harvest+of+fluorescent+proteins&rft.au=Patterson%2C+George+H&rft.aulast=Patterson&rft.aufirst=George&rft.date=2004-12-01&rft.volume=22&rft.issue=12&rft.spage=1524&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2Fnbt1204-1524 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Discosoma; directed evolution; Color; Protein interaction; Reviews; Fluorescence; red fluorescent protein; yellow fluorescent protein DO - http://dx.doi.org/10.1038/nbt1204-1524 ER - TY - JOUR T1 - EGR1 Is a Novel Target for AhR Agonists in Human Lung Epithelial Cells AN - 17710672; 6080034 AB - The transcription factor early growth response 1 (EGR1) was previously identified as a potential novel target of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in human lung epithelial cells by toxicogenomic analysis. EGR1 has been implicated in the pathogenesis of vascular disease and is altered by a number of factors that include stress, inflammation, and hypoxia. Depending on its downstream targets or protein interactions, EGR1 regulates important biological processes that include cell growth, apoptosis, and differentiation. The following experiments were conducted to determine if EGR1 is indeed a target of TCDD and polycyclic aromatic hydrocarbons (PAHs) that can act through a similar mechanism. Pulmonary epithelial cells were exposed to TCDD for 24 h and an increase in EGR1 mRNA was measured. In addition, EGR1 protein was increased by TCDD and PAHs that have binding affinity to the aryl hydrocarbon receptor. The transcriptional activity of the EGR1 promoter was measured with a luciferase construct; however, no increases in luciferase activity were detected in TCDD or PAH-treated cells. Using actinomycin to inhibit RNA synthesis, we found that TCDD increased the half-life of EGR1 mRNA from 13 to 22 min. Thus, the increase in EGR1 expression appears to be mediated through a post-transcriptional mechanism that leads to the higher EGR1 protein levels in TCDD and PAH treated cells, compared to vehicle treated cells. Increased expression of a transcription factor EGR1 with tumorigenic and other biological activities could contribute to the deleterious pulmonary effects of exposure to these environmental agents. JF - Toxicological Sciences AU - Martinez, Jeanelle M AU - Baek, Seung Joon AU - Mays, Donna M AU - Tithof, Patricia K AU - Eling, Thomas E AU - Walker, Nigel J AD - Laboratory of Computational Biology and Risk Analysis, NIEHS, Research Triangle Park, North Carolina, 27709 Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 429 EP - 435 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 82 IS - 2 SN - 1096-6080, 1096-6080 KW - Toxicology Abstracts KW - Epithelial cells KW - Polycyclic aromatic hydrocarbons KW - Apoptosis KW - TCDD KW - Vascular diseases KW - Inflammation KW - Differentiation KW - Lung KW - Hypoxia KW - Transcription factors KW - Aryl hydrocarbon receptors KW - Post-transcription KW - EGR-1 protein KW - Protein interaction KW - X 24155:Biochemistry KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17710672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=EGR1+Is+a+Novel+Target+for+AhR+Agonists+in+Human+Lung+Epithelial+Cells&rft.au=Martinez%2C+Jeanelle+M%3BBaek%2C+Seung+Joon%3BMays%2C+Donna+M%3BTithof%2C+Patricia+K%3BEling%2C+Thomas+E%3BWalker%2C+Nigel+J&rft.aulast=Martinez&rft.aufirst=Jeanelle&rft.date=2004-12-01&rft.volume=82&rft.issue=2&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - EGR-1 protein; TCDD; Lung; Epithelial cells; Transcription factors; Polycyclic aromatic hydrocarbons; Hypoxia; Inflammation; Vascular diseases; Differentiation; Post-transcription; Protein interaction; Apoptosis; Aryl hydrocarbon receptors ER - TY - JOUR T1 - Human Carcinogenic Risk Evaluation, Part V: The National Toxicology Program Vision for Assessing the Human Carcinogenic Hazard of Chemicals AN - 17708502; 6080025 AB - The National Toxicology Program (NTP) has over 25 years of experience in the design, performance, and interpretation of assays for identifying carcinogenic hazards to humans. Through the years we have examined alternative assays and adjunct assays to the standard rodent cancer bioassay including batteries of genetic toxicity tests and genetically modified mouse models. As our collective understanding of carcinogenesis advances, toxicologists and regulatory scientists will at some point begin to rely on mechanism-based biological observations rather than the two-year rodent bioassay to predict human cancer hazards. The goal of the NTP Vision for the 21st Century is to develop the science base that will advance the use of mechanism-based biological observations, eventually providing a replacement for disease-specific toxicology models in the protection of public health. JF - Toxicological Sciences AU - Bucher, John R AU - Portier, Christopher AD - National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 363 EP - 366 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 82 IS - 2 SN - 1096-6080, 1096-6080 KW - Health & Safety Science Abstracts; Toxicology Abstracts KW - Genotoxicity KW - Animal models KW - Cancer KW - Public health KW - Carcinogenesis KW - X 24230:Legislation & recommended standards KW - H 14000:Toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17708502?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Human+Carcinogenic+Risk+Evaluation%2C+Part+V%3A+The+National+Toxicology+Program+Vision+for+Assessing+the+Human+Carcinogenic+Hazard+of+Chemicals&rft.au=Bucher%2C+John+R%3BPortier%2C+Christopher&rft.aulast=Bucher&rft.aufirst=John&rft.date=2004-12-01&rft.volume=82&rft.issue=2&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Animal models; Genotoxicity; Carcinogenesis; Public health ER - TY - JOUR T1 - Resveratrol-Associated Renal Toxicity AN - 17702050; 6080099 AB - Resveratrol, (3,5,4'-trihydoxystilbene) a compound found in grapes, mulberries, and peanuts, has antimycotic, antiviral, and beneficial cardiovascular and cancer preventive activities. It is being developed for several clinical indications. To evaluate the potential toxicity of resveratrol, rats were administered by gavage 0, 300, 1000, and 3000 mg trans-resveratrol per kilogram body weight per day for 4 weeks. Most of the adverse events occurred in the rats administered 3000 mg per kilogram body weight per day. These included increased clinical signs of toxicity; reduced final body weights and food consumption; elevated BUN, creatinine, alkaline phosphatase, alanine aminotransferase, total bilirubin, and albumin; reduced hemoglobin, hematocrit, and red cell counts; and increased white cell counts. Increases in kidney weights and clinically significant renal lesions, including an increased incidence and severity of nephropathy, were observed. Diffuse epithelial hyperplasia in the bladder was considered, equivocal and of limited biological significance. No histological effects on the liver were observed, despite the clinical chemistry changes and increased liver weights in the females. Effects seen in the group administered 1000 mg resveratrol per kilogram body weight per day included reduced body weight gain (females only) and elevated white blood cell count (males only). Plasma resveratrol concentrations in blood collected 1 h after dose administration during week 4 were dose related but were relatively low given the high dosage levels; conjugates were not measured. Under the conditions of this study, the no observed adverse effect level was 300 mg resveratrol per kilogram body weight per day in rats. JF - Toxicological Sciences AU - Crowell, James A AU - Korytko, Peter J AU - Morrissey, Robert L AU - Booth, Tristan D AU - Levine, Barry S AD - Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 614 EP - 619 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 82 IS - 2 SN - 1096-6080, 1096-6080 KW - Peanut KW - Grapes KW - Toxicology Abstracts KW - Arachis hypogaea KW - Urinary bladder KW - trans-resveratrol KW - Toxicity KW - Alanine transaminase KW - Resveratrol KW - Food consumption KW - Hyperplasia KW - Creatinine KW - Alkaline phosphatase KW - Body weight KW - Nephropathy KW - Albumin KW - Liver KW - Kidney KW - Hematocrit KW - Body weight gain KW - Vitaceae KW - Side effects KW - X 24172:Plants KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17702050?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Resveratrol-Associated+Renal+Toxicity&rft.au=Crowell%2C+James+A%3BKorytko%2C+Peter+J%3BMorrissey%2C+Robert+L%3BBooth%2C+Tristan+D%3BLevine%2C+Barry+S&rft.aulast=Crowell&rft.aufirst=James&rft.date=2004-12-01&rft.volume=82&rft.issue=2&rft.spage=614&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vitaceae; Arachis hypogaea; Resveratrol; Body weight; Toxicity; Kidney; Liver; Alkaline phosphatase; Albumin; trans-resveratrol; Food consumption; Nephropathy; Alanine transaminase; Body weight gain; Side effects; Hyperplasia; Creatinine; Urinary bladder; Hematocrit ER - TY - JOUR T1 - Enhanced Acetaminophen Toxicity by Activation of the Pregnane X Receptor AN - 17701544; 6080027 AB - The pregnane X receptor (PXR) is a ligand-activated transcription factor and member of the nuclear receptor superfamily. Activation of PXR represents an important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl- p-benzoquinone imine (NAPQI). Therefore, it was hypothesized that activation of PXR plays a major role in APAP-induced hepatotoxicity. Pretreatment with the PXR activator, pregnenolone 16alpha-carbonitrile (PCN), markedly enhanced APAP- induced hepatic injury, as revealed by increased serum ALT levels and hepatic centrilobular necrosis, in wild-type but not in PXR-null mice. Further analysis showed that following PCN treatment, PXR-null mice had lower CYP3A11 expression, decreased NAPQI formation, and increased maintenance of hepatic glutathione content compared to wild-type mice. Thus, these results suggest that PXR plays a critical role in APAP-induced hepatic toxicity, probably by inducing CYP3A11 expression and hence increasing bioactivation. JF - Toxicological Sciences AU - Guo, Grace L AU - Moffit, Jeff S AU - Nicol, Christopher J AU - Ward, Jerrold M AU - Aleksunes, Lauren A AU - Slitt, Angela L AU - Kliewer, Steven A AU - Manautou, Jose E AU - Gonzalez, Frank J AD - Laboratory of Metabolism, CCR, NCI, NIH, Bethesda, Maryland Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 374 EP - 380 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 82 IS - 2 SN - 1096-6080, 1096-6080 KW - pregnenolone 16^a-carbonitrile KW - N-acetyl-p-benzoquinone imine KW - pregnenolone 16 alpha -carbonitrile KW - Toxicology Abstracts KW - Necrosis KW - Glutathione KW - Nuclear receptors KW - Transcription factors KW - Cytochrome P450 KW - pregnane X receptors KW - hepatotoxicity KW - Acetaminophen KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17701544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Enhanced+Acetaminophen+Toxicity+by+Activation+of+the+Pregnane+X+Receptor&rft.au=Guo%2C+Grace+L%3BMoffit%2C+Jeff+S%3BNicol%2C+Christopher+J%3BWard%2C+Jerrold+M%3BAleksunes%2C+Lauren+A%3BSlitt%2C+Angela+L%3BKliewer%2C+Steven+A%3BManautou%2C+Jose+E%3BGonzalez%2C+Frank+J&rft.aulast=Guo&rft.aufirst=Grace&rft.date=2004-12-01&rft.volume=82&rft.issue=2&rft.spage=374&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Acetaminophen; pregnane X receptors; Necrosis; Cytochrome P450; Transcription factors; hepatotoxicity; Nuclear receptors; Glutathione ER - TY - JOUR T1 - The Accuracy of Extended Histopathology to Detect Immunotoxic Chemicals AN - 17699086; 6080056 AB - The accuracy of extended histopathology to detect immunotoxic chemicals in female B6C3F1 mice was evaluated under the auspices of the National Toxicology Program (NTP). A workgroup was formed consisting of four pathologists who conducted extended histopathological evaluation of lymphoid tissues obtained from a subset of NTP toxicology studies, in which previously detailed immunotoxicity assessment was performed. In addition, a positive control data set of three known immunosuppressive agents, one negative control data set, and an additional negative control group composed of the vehicle only treated groups were included. Data obtained from extended histopathology evaluations were compared to more traditional immune test results (both functional and nonfunctional) from previously conducted immunotoxicity assessments. Analyses of the data indicated that the ability to identify immunotoxic chemicals using histological endpoints decreased linearly as the level of stringency used to determine significant histopathological changes increased. A relatively high (80%) accuracy level was achieved when histological changes were considered in toto (i.e., any histological abnormality in the three tissues examined), using minimal or mild criteria for scoring. When minimal or mild histological changes were considered significant for a specific tissue, a 60% level of accuracy in identifying immunotoxic chemicals was obtained as compared to a 90% accuracy level that was achieved with this data set using the antibody plaque forming cell response, considered to represent the most predictive functional test. A minimal classification was obtained in the analyses of the negative control groups, suggesting that use of the minimal classification for hazard identification is inappropriate as it will likely result in a high incidence of false positives. This was not the case when mild classifications were used as an indicator of significance, which in most instances allowed the successful identification of negatives. When moderate to marked histopathological changes were used to identify immunotoxic chemicals, the level of accuracy that could be achieved was poor. A considerably higher level of accuracy was obtained for the positive control data set than the test chemical data set suggesting that the ability to detect an immunotoxic agent histologically is proportional to the potency of the immunotoxic agent. Comparison of immune function test results and histopathological results obtained from the high-dose treatment groups and the lower-dose treatment group did not reveal any significant differences between the two endpoints to predict immunotoxicity as a function of dose. Of the three lymphoid organs examined, (i.e., lymph node, thymus, and spleen), the most consistent and discernible histological lesions were observed in the thymus cortical region. These lesions correlated with thymus: body weight ratios and to a slightly lesser extent, the antibody plaque forming cell response. Addition of general toxicological endpoints such as body weight and leukocyte counts did not significantly improve the sensitivity of extended histopathology for this data set. Taken together, these data suggest that, while not as sensitive as functional analyses, extended histopathology may provide a reasonable level of accuracy as a screening test to identify immunotoxic chemicals, provided the level of stringency used to score histological lesions is carefully considered to allow for detection of immunotoxic agents while limiting false positives. JF - Toxicological Sciences AU - Germolec AU - Kashon, M AU - Nyska, A AU - Kuper, C F AU - Portier, C AU - Kommineni, C AU - Johnson, KA AU - Luster, MI AD - Laboratory of Molecular Toxicology/National Toxicology Program, National Institute of Environmental Health Sciences, RTP, North Carolina Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 504 EP - 514 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 82 IS - 2 SN - 1096-6080, 1096-6080 KW - Toxicology Abstracts KW - Immunotoxicity KW - Histology KW - Body weight KW - Leukocytes KW - Thymus KW - Spleen KW - Immunosuppressive agents KW - Lymph nodes KW - Lymphoid tissue KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17699086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=The+Accuracy+of+Extended+Histopathology+to+Detect+Immunotoxic+Chemicals&rft.au=Germolec%3BKashon%2C+M%3BNyska%2C+A%3BKuper%2C+C+F%3BPortier%2C+C%3BKommineni%2C+C%3BJohnson%2C+KA%3BLuster%2C+MI&rft.aulast=Germolec&rft.aufirst=&rft.date=2004-12-01&rft.volume=82&rft.issue=2&rft.spage=504&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Immunotoxicity; Thymus; Body weight; Immunosuppressive agents; Lymphoid tissue; Lymph nodes; Histology; Leukocytes; Spleen ER - TY - JOUR T1 - The effect of the physical characteristics of hydroxyapatite particles on human monocytes IL-18 production in vitro AN - 17572736; 5929295 AB - Hydroxyapatite (HA) is widely used to coat the metal parts of prosthetic implants in order to improve their biocompatibility and as a bone defect filling material. HA has been demonstrated to produce particles at the prosthetic interface that lead to an activation of phagocytic cells that induce a cascade reaction leading to bone resorption and aseptic loosening. Monocytes/macrophages are commonly observed in the interface tissue, and are among the first cells to colonize the inflammatory site where they play a key role in the immune response. IL-18 is a pro-inflammatory cytokine. Monocytes/macrophages were described as IL-18 producing cells. IL-18 works antagonistically to IL-6, which activates osteoclastogenesis. In the present study, we investigated the ability of HA particles to induce the production of active IL-18 by human monocytes according to particle characteristics (size, sintering temperature and shape). Our study demonstrates, for the first time, that HA particles are capable of stimulating the production of the proinflammatory cytokine IL-18 in human monocytes according to their particle characteristics. The expression and the production of IL-18 was modified by the parameter studied. The difference observed between the expression and the production could be explain by the production of ICE. The needle shaped particles induced the larger production of IL-18. JF - Biomaterials AU - Grandjean-Laquerriere, A AU - Laquerriere, P AU - Laurent-Maquin, D AU - Guenounou, M AU - Phillips, T M AD - Ultramicro Analytical Immunochemistry Resource, Division of Bioengineering and Physical Science, Office of Research Services, National Institutes of Health, Bethesda, MD 20892, USA, alexia.grandjean@univ-reims.fr Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 5921 EP - 5927 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 25 IS - 28 SN - 0142-9612, 0142-9612 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Interleukin 6 KW - Macrophages KW - Metals KW - Inflammation KW - Hydroxyapatite KW - Interleukin 18 KW - Biomaterials KW - Bone resorption KW - Monocytes KW - Osteoclastogenesis KW - Bone implants KW - Prosthetics 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/17572736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+effect+of+the+physical+characteristics+of+hydroxyapatite+particles+on+human+monocytes+IL-18+production+in+vitro&rft.au=Grandjean-Laquerriere%2C+A%3BLaquerriere%2C+P%3BLaurent-Maquin%2C+D%3BGuenounou%2C+M%3BPhillips%2C+T+M&rft.aulast=Grandjean-Laquerriere&rft.aufirst=A&rft.date=2004-12-01&rft.volume=25&rft.issue=28&rft.spage=5921&rft.isbn=&rft.btitle=&rft.title=Biomaterials&rft.issn=01429612&rft_id=info:doi/10.1016%2Fj.biomaterials.2004.02.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Interleukin 18; Monocytes; Hydroxyapatite; Prosthetics; Inflammation; Macrophages; Bone implants; Metals; Interleukin 6; Biomaterials; Bone resorption; Osteoclastogenesis DO - http://dx.doi.org/10.1016/j.biomaterials.2004.02.003 ER - TY - JOUR T1 - Physical Activity as a Predictor of Body Composition in American Indian Children AN - 17522644; 6173626 AB - OBJECTIVE: To examine physical activity in second grade American Indian children as a predictor of percentage body fat 3 years later. RESEARCH METHODS AND PROCEDURES: Physical activity was assessed as average vector magnitude (AVM) counts from an accelerometer in 454 second grade children as part of the Pathways study. BMI was assessed, and skinfolds and bioelectrical impedance were used to estimate fat mass, fat-free body mass, and percentage body fat in validated prediction equations. Associations were examined using mixed models regression controlling for baseline body composition. RESULTS: In normal-weight children, higher AVM counts were significantly associated with decreases in percentage body fat. Among overweight children, higher AVM counts were significantly associated with increases in BMI, fat mass, and fat-free mass but not percentage body fat. DISCUSSION: Higher physical activity levels in second grade were associated with lower levels of percentage body fat in fifth grade in normal-weight but not in overweight children. BMI showed no association with physical activity among normal-weight children, and increases in BMI were associated with increasing amounts of physical activity among overweight children. These findings emphasize the importance of valid body composition measures and may indicate important differences in associations between physical activity and adiposity in normal-weight as compared with overweight children. JF - Obesity Research AU - Stevens, June AU - Suchindran, Chirayath AU - Ring, Kim AU - Baggett, Christopher D AU - Jobe, Jared B AU - Story, Mary AU - Thompson, Janice AU - Going, Scott B AU - Caballero, Benjamin AD - Departments of Nutrition and Epidemiology, Biostatistics, and. Epidemiology, University of North Carolina, Chapel Hill, North Carolina. National Heart, Lung, and Blood Institute. Division of Epidemiology, University of Minnesota, Minneapolis, Minnesota. Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico. Department of Physiology, University of Arizona, Tucson, Arizona. Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland. Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 1974 EP - 1980 PB - North American Association for the Study of Obesity, 1090 Amsterdam Ave., Ste. 14K New York NY 10025 USA, [mailto:helener@mindspring.com], [URL:http://www.naaso.org] VL - 12 IS - 12 SN - 1071-7323, 1071-7323 KW - Physical Education Index KW - Body composition (measurement) KW - Obesity KW - Body mass KW - Exercise KW - Children KW - Ethnic groups KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17522644?accountid=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+Research&rft.atitle=Physical+Activity+as+a+Predictor+of+Body+Composition+in+American+Indian+Children&rft.au=Stevens%2C+June%3BSuchindran%2C+Chirayath%3BRing%2C+Kim%3BBaggett%2C+Christopher+D%3BJobe%2C+Jared+B%3BStory%2C+Mary%3BThompson%2C+Janice%3BGoing%2C+Scott+B%3BCaballero%2C+Benjamin&rft.aulast=Stevens&rft.aufirst=June&rft.date=2004-12-01&rft.volume=12&rft.issue=12&rft.spage=1974&rft.isbn=&rft.btitle=&rft.title=Obesity+Research&rft.issn=10717323&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Children; Exercise; Obesity; Body composition (measurement); Ethnic groups; Body mass ER - TY - JOUR T1 - Assay for Ubiquitin Ligase Activity: High-Throughput Screen for Inhibitors of HDM2 AN - 17415068; 6536043 AB - An assay for the autoubiquitination activity of the E3 ligase HDM2 (Mdm2) was developed and adapted to a high-throughput format to identify inhibitors of this activity. The assay can also be used to measure the activity of other E3s and may be useful in finding both inhibitors and activators of a wide range of different ubiquitin ligases. JF - Journal of Biomolecular Screening AU - Davydov, I V AU - Woods, D AU - Safiran, Y J AU - Oberoi, P AU - Fearnhead, HO AU - Fang, S AU - Jensen, J P AU - Weissman, A M AU - Kenten, J H AU - Vousden, KH AD - Regulation of Cell Growth Laboratory and Laboratory of Protein Dynamics and Signaling, NCI Center for Cancer Research, Frederick, MD, USA, k.vousden@beatson.gla.ac.uk Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 695 EP - 703 VL - 9 IS - 8 SN - 1087-0571, 1087-0571 KW - Ubiquitin-protein ligase inhbitors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - MDM2 protein KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17415068?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biomolecular+Screening&rft.atitle=Assay+for+Ubiquitin+Ligase+Activity%3A+High-Throughput+Screen+for+Inhibitors+of+HDM2&rft.au=Davydov%2C+I+V%3BWoods%2C+D%3BSafiran%2C+Y+J%3BOberoi%2C+P%3BFearnhead%2C+HO%3BFang%2C+S%3BJensen%2C+J+P%3BWeissman%2C+A+M%3BKenten%2C+J+H%3BVousden%2C+KH&rft.aulast=Davydov&rft.aufirst=I&rft.date=2004-12-01&rft.volume=9&rft.issue=8&rft.spage=695&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biomolecular+Screening&rft.issn=10870571&rft_id=info:doi/10.1177%2F1087057104267956 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - MDM2 protein DO - http://dx.doi.org/10.1177/1087057104267956 ER - TY - JOUR T1 - Simultaneous MRI acquisition of blood volume, blood flow, and blood oxygenation information during brain activation AN - 17390133; 6495929 AB - Simultaneous acquisition of complementary functional hemodynamic indices reflecting different aspects of brain activity would be a valuable tool for functional brain-imaging studies offering enhanced detection power and improved data interpretation. As such, a new MRI technique is presented that is able to achieve concurrent acquisition of three hemodynamic images based primarily on the changes of cerebral blood volume, blood flow, and blood oxygenation, respectively, associated with brain activation. Specifically, an inversion recovery pulse sequence has been designed to measure VASO (vascular space occupancy), ASL (arterial spin labeling) perfusion, and BOLD (blood-oxygenation-level-dependent) signals in a single scan. The MR signal characteristics in this sequence were analyzed, and image parameters were optimized for the simultaneous acquisition of these functional images. The feasibility and efficacy of the new technique were assessed by brain activation experiments with visual stimulation paradigms. Experiments on healthy volunteers showed that this technique provided efficient image acquisition, and thus higher contrast-to-noise ratio per unit time, compared with conventional techniques collecting these functional images separately. In addition, it was demonstrated that the proposed technique was able to be utilized in event-related functional MRI experiments, with potential advantages of obtaining accurate transient information of the activation-induced hemodynamic responses. JF - Magnetic Resonance in Medicine AU - Yang, Yihong AU - Gu, Hong AU - Stein, Elliot A AD - Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, 5500 Nathan Shock Drive, Building C, Room 383, Baltimore, MD 21224, USA, yihongyang@intra.nida.nih.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 1407 EP - 1417 PB - John Wiley & Sons, Ltd. VL - 52 IS - 6 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Visual stimuli KW - Perfusion KW - Blood flow KW - Functional magnetic resonance imaging KW - Magnetic resonance imaging KW - Brain KW - Hemodynamics KW - N.M.R. 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/17390133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Simultaneous+MRI+acquisition+of+blood+volume%2C+blood+flow%2C+and+blood+oxygenation+information+during+brain+activation&rft.au=Yang%2C+Yihong%3BGu%2C+Hong%3BStein%2C+Elliot+A&rft.aulast=Yang&rft.aufirst=Yihong&rft.date=2004-12-01&rft.volume=52&rft.issue=6&rft.spage=1407&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20302 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-05-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Visual stimuli; Perfusion; Blood flow; Functional magnetic resonance imaging; Magnetic resonance imaging; Brain; Hemodynamics; N.M.R.; Vascular system DO - http://dx.doi.org/10.1002/mrm.20302 ER - TY - JOUR T1 - Functional optical detection based on pH dependent fluorescence lifetime AN - 17381245; 6473047 AB - Detection of possible alterations of physiological parameters (e.g., pH and temperature), resulting from malignant transformation of initially healthy tissue, can be a powerful diagnostic tool for earlier cancer detection. Such variations can be observed by comparing these parameters with those of healthy tissue surrounding the abnormality. Time-resolved spectroscopy of specifically targeted fluorescent-labeled antibodies can be sensitive to such variations and provide a high-resolution functional image of the region of interest. The goal of this study was to establish a forward experimental setup for calibration of the lifetime dependencies of near-IR fluorescent dyes on physiological parameters, and to develop analytical solutions, taking into account the effects of light propagation in turbid media (e.g., tissue), that was able to extract an original lifetime fluorescence signal from time-of-flight intensity distributions, measured in vivo from a deeply embedded live organ for further analysis. Tissue-like phantoms with embedded fluorescent dyes and background optical properties simulating those of live tissues were designed and created. Fluorescence decay curves were measured for different fluorophore positions, and pH values. Those measurements were made with a system based on a time-correlated single photon counting (TCSPC) instrument and a tunable femtosecond Ti-Sapphire system built by our group. Decay curves were recorded for fluorophore depths of up to 5 mm and source-detector separation of 7 mm. It was shown that a forward model, based on the random walk theory, adequately described the experimental data. Measured pH dependencies of the fluorescence lifetime were characterized for two different dyes. Good correlation between experimental data and predictions of the theoretical model allows the use of close-form analytical solutions to separate the effects of photon time delays due to multiple scattering in tissues from the original intensity fluorescence time decay curve, determined by the fluorophore itself and its immediate surroundings. It is the latter dependence that can be diagnostically important. Experimentally obtained scaling between lifetime and a parameter of interest can be used in vivo to obtain a map of physiological parameter changes which can serve as a base for an in vivo specific diagnostic system. JF - Lasers in Surgery and Medicine AU - Gannot, Israel AU - Ron, Izhar AU - Hekmat, Farid AU - Chernomordik, Victor AU - Gandjbakhche, Amir AD - Lasers and Optics in Medicine Laboratory, Department of Biomedical Engineering, Faculty of Engineering Tel-Aviv University, Tel-Aviv 69978, Israel, gannoti@mail.nih.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 342 EP - 348 PB - John Wiley & Sons, Ltd. VL - 35 IS - 5 SN - 0196-8092, 0196-8092 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Temperature effects KW - Fluorescence KW - Photons KW - Optical properties KW - fluorophores KW - Spectroscopy KW - Cancer KW - Antibodies KW - Dyes KW - Fluorescent indicators KW - Lasers KW - pH effects 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/17381245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lasers+in+Surgery+and+Medicine&rft.atitle=Functional+optical+detection+based+on+pH+dependent+fluorescence+lifetime&rft.au=Gannot%2C+Israel%3BRon%2C+Izhar%3BHekmat%2C+Farid%3BChernomordik%2C+Victor%3BGandjbakhche%2C+Amir&rft.aulast=Gannot&rft.aufirst=Israel&rft.date=2004-12-01&rft.volume=35&rft.issue=5&rft.spage=342&rft.isbn=&rft.btitle=&rft.title=Lasers+in+Surgery+and+Medicine&rft.issn=01968092&rft_id=info:doi/10.1002%2Flsm.20101 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-03-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Fluorescence; pH effects; fluorophores; Fluorescent indicators; Photons; Optical properties; Lasers; Dyes; Temperature effects; Antibodies; Spectroscopy; Cancer DO - http://dx.doi.org/10.1002/lsm.20101 ER - TY - JOUR T1 - Manganese Enhanced Magnetic Resonance Imaging AN - 17329788; 6204174 AB - Manganese is an essential metal that participates as a co-factor in a number of critical biological functions such as electron transport, detoxification of free radicals, and synthesis of neurotransmitters. Like other heavy metals, high concentrations of manganese are toxic. For example, chronic overexposure to manganese leads to movement disorders. In order to maintain this balance between being an essential participant in enzyme function and being a toxic heavy metal, a rich biology has evolved to transport and store manganese. Paramagnetic forms of manganese ions are potent MRI relaxation agents. Indeed, Mn2+ was the first contrast agent proposed for use in MRI. Recently, there is renewed interest in combining the strong MRI relaxation effects of Mn2+ with its unique biology in order to expand the range of information that can be measured by MRI. Manganese Enhanced MRI is being developed to give unique tissue contrast, assess tissue viability, act as a surrogate marker of calcium influx into cells and trace neuronal connections. In this article we review recent work and point out prospects for the future uses of manganese enhanced MRI. JF - Current Pharmaceutical Biotechnology AU - Lee, J H AU - Koretsky AD - LFMI, NINDS, Building 10, B1D118, 10 Center Drive, Bethesda, MD 20812, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 529 EP - 537 VL - 5 IS - 6 SN - 1389-2010, 1389-2010 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/17329788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Pharmaceutical+Biotechnology&rft.atitle=Manganese+Enhanced+Magnetic+Resonance+Imaging&rft.au=Lee%2C+J+H%3BKoretsky&rft.aulast=Lee&rft.aufirst=J&rft.date=2004-12-01&rft.volume=5&rft.issue=6&rft.spage=529&rft.isbn=&rft.btitle=&rft.title=Current+Pharmaceutical+Biotechnology&rft.issn=13892010&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-02-01 N1 - SuppNotes - MR Contrast Agents for Molecular and Cellular Imaging. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Dendrimer-Based Nanosized MRI Contrast Agents AN - 17321210; 6204175 AB - Paramagnetic metals can induce T1 shortening by interaction with free water molecules. Two metal ions, Gadolinium and Manganese, are currently available for human use. Gadolinium-based MRI contrast agents (CAs) can operate using a similar to 100-fold lower concentration of Gadolinium ions in comparison to the necessary concentration of Iodine atoms employed in CT imaging in the tissues. Therefore, numerous macromolecular MRI CAs prepared employing relatively simple chemistry are readily available that can provide sufficient enhancement for multiple applications. Herein, we describe the synthesis, characteristics, and potential applications of dendrimer-based macromolecular MRI CAs in our recently reported libraries. This entire series of dendrimer-based macromolecular MRI CAs have a spherical shape and possess similar surface charges. Changes in molecular size altered the route of excretion. Smaller sized contrast agents, of less than 60 kD molecular weight, were excreted through the kidney resulting in these agents being potentially suitable as functional renal contrast agents. Less hydrophilic and larger sized contrast agents were found better suited for use as blood pool contrast agents. Hydrophobic variants of CAs formed with polypropylenimine diaminobutane dendrimer cores quickly accumulated in the liver and can function as liver contrast agents. Larger hydrophilic agents are also useful for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents and might also be employed as therapeutic drugs for either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy. JF - Current Pharmaceutical Biotechnology AU - Kobayashi, H AU - Brechbiel, M W AD - Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bldg. 10, Room B3B69, MCS 1002, 10 Center Dr., Bethesda, MD 20892-1002, USA Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 539 EP - 549 VL - 5 IS - 6 SN - 1389-2010, 1389-2010 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/17321210?accountid=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=Criminal+Justice+and+Behavior&rft.atitle=Less+lethal+force+policy+and+police+officer+perceptions%3A+A+multisite+examination&rft.au=Terrill%2C+William%3BPaoline%2C+Eugene+A.%2C+III&rft.aulast=Terrill&rft.aufirst=William&rft.date=2013-10-01&rft.volume=40&rft.issue=10&rft.spage=1109&rft.isbn=&rft.btitle=&rft.title=Criminal+Justice+and+Behavior&rft.issn=00938548&rft_id=info:doi/10.1177%2F0093854813485074 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-02-01 N1 - SuppNotes - MR Contrast Agents for Molecular and Cellular Imaging. N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Retrieving definitional content for ontology development AN - 17311096; 6102298 AB - Ontology construction requires an understanding of the meaning and usage of its encoded concepts. While definitions found in dictionaries or glossaries may be adequate for many concepts, the actual usage in expert writing could be a better source of information for many others. The goal of this paper is to describe an automated procedure for finding definitional content in expert writing. The approach uses machine learning on phrasal features to learn when sentences in a book contain definitional content, as determined by their similarity to glossary definitions provided in the same book. The end result is not a concise definition of a given concept, but for each sentence, a predicted probability that it contains information relevant to a definition. The approach is evaluated automatically for terms with explicit definitions, and manually for terms with no available definition. JF - Computational Biology and Chemistry AU - Smith, L AU - Wilbur, W J AD - National Center for Biotechnology Information, NIH, NLM, Building 38A, 8600 Rockville Pike, Bethesda, MD 20894, USA, lsmith@ncbi.nlm.nih.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 387 EP - 391 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 28 IS - 5-6 SN - 1476-9271, 1476-9271 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/17311096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Computational+Biology+and+Chemistry&rft.atitle=Retrieving+definitional+content+for+ontology+development&rft.au=Smith%2C+L%3BWilbur%2C+W+J&rft.aulast=Smith&rft.aufirst=L&rft.date=2004-12-01&rft.volume=28&rft.issue=5-6&rft.spage=387&rft.isbn=&rft.btitle=&rft.title=Computational+Biology+and+Chemistry&rft.issn=14769271&rft_id=info:doi/10.1016%2Fj.compbiolchem.2004.09.007 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.compbiolchem.2004.09.007 ER - TY - JOUR T1 - Prenatal diagnosis of membranous ventricular septal aneurysms and their association with absence of atrioventricular valve 'offsetting' AN - 17137210; 6786557 AB - Congenital aneurysm of the membranous portion of the ventricular septum in association with absence of atrioventricular valve 'offsetting' was diagnosed in two fetuses at 29 and 34 weeks. In the first case the fetus had a normal karyotype and no other structural heart defects, whereas in the second case there was a partial deletion of the long arm of chromosome 5 and an absent pulmonary valve syndrome. The association of absence of 'offsetting' with aneurysms of the membranous ventricular septum may represent spontaneous closure of ventricular septal defects initially extended to the inlet. JF - Ultrasound in Obstetrics and Gynecology AU - Espinoza, J AU - Kalache, K AU - Goncalves, L F AU - Lee, W AU - Chaiworapongsa, T AU - Schoen, M L AU - Devers, P AU - Treadwell, M AU - Mazor, M AU - Romero, R AD - Perinatology Research Branch, NICHD, NIH, DHHS, 4707 St Antoine Boulevard, Detroit, MI 48201, USA, warfiela@mail.nih.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 787 EP - 792 PB - John Wiley & Sons, Ltd. VL - 24 IS - 7 SN - 0960-7692, 0960-7692 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Heart KW - Aneurysm KW - Gynecology KW - Prenatal diagnosis KW - chromosome 5 KW - Karyotypes KW - Fetuses KW - Lung KW - Chromosome deletion KW - Septum KW - Ultrasound KW - Obstetrics KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17137210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Ultrasound+in+Obstetrics+and+Gynecology&rft.atitle=Prenatal+diagnosis+of+membranous+ventricular+septal+aneurysms+and+their+association+with+absence+of+atrioventricular+valve+%27offsetting%27&rft.au=Espinoza%2C+J%3BKalache%2C+K%3BGoncalves%2C+L+F%3BLee%2C+W%3BChaiworapongsa%2C+T%3BSchoen%2C+M+L%3BDevers%2C+P%3BTreadwell%2C+M%3BMazor%2C+M%3BRomero%2C+R&rft.aulast=Espinoza&rft.aufirst=J&rft.date=2004-12-01&rft.volume=24&rft.issue=7&rft.spage=787&rft.isbn=&rft.btitle=&rft.title=Ultrasound+in+Obstetrics+and+Gynecology&rft.issn=09607692&rft_id=info:doi/10.1002%2Fuog.1769 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-07-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Heart; Gynecology; Aneurysm; Lung; Chromosome deletion; Prenatal diagnosis; Septum; Obstetrics; Karyotypes; chromosome 5; Ultrasound; Fetuses DO - http://dx.doi.org/10.1002/uog.1769 ER - TY - JOUR T1 - Model of full-length HIV-1 integrase complexed with viral DNA as template for anti-HIV drug design AN - 17098322; 6732686 AB - We report structural models of the full-length integrase enzyme (IN) of the human immunodeficiency virus type 1 (HIV-1) and its complex with viral and human DNA. These were developed by means of molecular modeling techniques using all available experimental evidence, including X-ray crystallographic and NMR structures of portions of the full-length protein. Special emphasis was placed on obtaining a model of the enzyme's active site with the viral DNA apposed to it, based on the hypothesis that such a model would allow structure-based design of inhibitors that retain activity in vivo. This was because bound DNA might be present in vivo after 3'-processing but before strand transfer. These structural models were used to study the potential binding modes of various diketo-acid HIV-1 IN inhibitors (many of them preferentially inhibiting strand transfer) for which no experimentally derived complexed structures are available. The results indicate that the diketo-acid IN inhibitors probably chelate the metal ion in the catalytic site and also prevent the exposure of the 3'-processed end of the viral DNA to human DNA. JF - Journal of Computer-Aided Molecular Design AU - Karki, Rajeshri G AU - Tang, Yun AU - Burke, Terrence R AU - Nicklaus, Marc C AD - National Institutes of Health, DHHS, 376 Boyles Street, Frederick, MD, 21702, USA, mn1@helix.nih.gov Y1 - 2004/12// PY - 2004 DA - Dec 2004 SP - 739 EP - 760 PB - Springer-Verlag (Heidelberg), Tiergartenstrasse 17 Heidelberg 69121 Germany, [mailto:subscriptions@springer.de], [URL:http://www.springer.de/] VL - 18 IS - 12 SN - 0920-654X, 0920-654X KW - HIV-1 KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Metals KW - Molecular modelling KW - Enzymes KW - Drug development KW - Models KW - Human immunodeficiency virus KW - Ionizing radiation KW - Human immunodeficiency virus 1 KW - DNA KW - N.M.R. KW - Chelates KW - Active sites KW - Integrase KW - W4 130:General Biomedical Engineering: Tools & Techniques KW - V 22002:AIDS: Molecular and in vitro aspects KW - W3 33310:Enzymes and cofactors KW - W 30965:Miscellaneous, Reviews KW - N 14810:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17098322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Computer-Aided+Molecular+Design&rft.atitle=Model+of+full-length+HIV-1+integrase+complexed+with+viral+DNA+as+template+for+anti-HIV+drug+design&rft.au=Karki%2C+Rajeshri+G%3BTang%2C+Yun%3BBurke%2C+Terrence+R%3BNicklaus%2C+Marc+C&rft.aulast=Karki&rft.aufirst=Rajeshri&rft.date=2004-12-01&rft.volume=18&rft.issue=12&rft.spage=739&rft.isbn=&rft.btitle=&rft.title=Journal+of+Computer-Aided+Molecular+Design&rft.issn=0920654X&rft_id=info:doi/10.1007%2Fs10822-005-0365-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Molecular modelling; Metals; Ionizing radiation; DNA; Enzymes; N.M.R.; Drug development; Active sites; Chelates; Integrase; Models; Human immunodeficiency virus; Human immunodeficiency virus 1 DO - http://dx.doi.org/10.1007/s10822-005-0365-5 ER - TY - JOUR T1 - Interspecies communication in Streptococcus gordonii-Veillonella atypica biofilms: Signaling in flow conditions requires juxtaposition AN - 20218769; 6099134 AB - During the development of human oral biofilm communities, the spatial arrangement of the bacteria is thought to be driven by metabolic interactions between them. Streptococcus gordonii and Veillonella atypica, two early colonizing members of the dental plaque biofilm, have been postulated to participate in metabolic communication; S. gordonii ferments carbohydrates to form lactic acid, which is a preferred fermentation substrate for V. atypica. We found that, during agar-plate coculture of these organisms, a signaling event occurs that results in increased expression of the S. gordonii alpha-amylase- encoding gene amyB. Confocal scanning laser microscopy of coculture flowcell- grown biofilms using human saliva as the sole nutrient showed that V. atypica caused S. gordonii to increase expression of a PamyB-'gfp transcriptional fusion in a spatially resolved fashion. In this open system, only those streptococci in mixed-species microcolonies containing V. atypica expressed GFP; nearby S. gordonii colonies that lacked V. atypica did not express GFP. In a closed system containing S. gordonii and V. atypica, flow cytometric analysis showed that S. gordonii containing the PamyB-'gfp reporter plasmid exhibited mean fluorescence levels 20-fold higher than did S. gordonii that had not been incubated with V. atypica. Thus, in a closed system where a diffusible signal can accumulate above a required threshold, interspecies signaling mediates a change in gene expression. We provide evidence that, in open systems like those that predominate in natural biofilms, diffusible signals between species are designed to function over short distances, on the order of 1 mu m. JF - Proceedings of the National Academy of Sciences, USA AU - Egland, Paul G AU - Palmer, Robert J AU - Kolenbrander, Paul E AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD Y1 - 2004/11/30/ PY - 2004 DA - 2004 Nov 30 SP - 16917 EP - 16922 PB - National Academy of Sciences, 2101 Constitution Ave. Washington DC 20418 USA VL - 101 IS - 48 SN - 0027-8424, 0027-8424 KW - Ecology Abstracts; Biotechnology and Bioengineering Abstracts; ASFA 1: Biological Sciences & Living Resources; Oceanic Abstracts; Microbiology Abstracts B: Bacteriology KW - Teeth KW - Fermentation KW - Communication KW - Nutrients KW - Flow cytometry KW - Gene expression KW - Veillonella atypica KW - Colonies KW - Streptococcus gordonii KW - Substrate preferences KW - Biofilms KW - Carbohydrates KW - Fluorescence KW - Lactate KW - Transcription KW - Dental plaque KW - Plasmids KW - Veillonella KW - Lactic acid KW - Saliva KW - Open systems KW - Signal transduction KW - Q1 08206:Physiology, biochemistry, biophysics KW - O 1070:Ecology/Community Studies KW - W 30950:Waste Treatment & Pollution Clean-up KW - D 04040:Ecosystem and Ecology Studies KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20218769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interspecies+communication+in+Streptococcus+gordonii-Veillonella+atypica+biofilms%3A+Signaling+in+flow+conditions+requires+juxtaposition&rft.au=Egland%2C+Paul+G%3BPalmer%2C+Robert+J%3BKolenbrander%2C+Paul+E&rft.aulast=Egland&rft.aufirst=Paul&rft.date=2004-11-30&rft.volume=101&rft.issue=48&rft.spage=16917&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-08-01 N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Gene expression; Teeth; Substrate preferences; Fermentation; Lactate; Carbohydrates; Biofilms; Plasmids; Open systems; Fluorescence; Communication; Transcription; Nutrients; Dental plaque; Flow cytometry; Colonies; Lactic acid; Saliva; Signal transduction; Veillonella atypica; Streptococcus gordonii; Veillonella ER - TY - JOUR T1 - GalR represses galP1 by inhibiting the rate-determining open complex formation through RNA polymerase contact: a GalR negative control mutant. AN - 67062995; 15533432 AB - GalR represses the galP1 promoter by a DNA looping-independent mechanism. Equilibrium binding of GalR and RNA polymerase to DNA, and real-time kinetics of base-pair distortion (isomerization) showed that the equilibrium dissociation constant of RNA polymerase-P1 closed complexes is largely unaffected in the presence of saturating GalR, indicating that mutual antagonism (steric hindrance) of the regulator and the RNA polymerase does not occur at this promoter. In fluorescence kinetics with 2-AP labeled P1 DNA, GalR inhibited the slower of the two-step base-pair distortion process. We isolated a negative control GalR mutant, S29R, which while bound to the operator DNA was incapable of repression of P1. Based on these results and previous demonstration that repression requires the C-terminal domain of the alpha subunit (alpha-CTD) of RNA polymerase, we propose that GalR establishes contact with alpha-CTD at the last resolved isomerization intermediate, forming a kinetic trap. JF - Journal of molecular biology AU - Roy, Siddhartha AU - Semsey, Szabolcs AU - Liu, Mofang AU - Gussin, Gary N AU - Adhya, Sankar AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/11/26/ PY - 2004 DA - 2004 Nov 26 SP - 609 EP - 618 VL - 344 IS - 3 SN - 0022-2836, 0022-2836 KW - Escherichia coli Proteins KW - 0 KW - Galactose repressor proteins KW - Repressor Proteins KW - DNA KW - 9007-49-2 KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Index Medicus KW - Promoter Regions, Genetic KW - Base Sequence KW - Fluorescence Polarization KW - Electrophoresis, Polyacrylamide Gel KW - Kinetics KW - DNA Footprinting KW - Molecular Sequence Data KW - Transcription, Genetic KW - Protein Binding KW - Mutagenesis KW - Repressor Proteins -- physiology KW - DNA-Directed RNA Polymerases -- metabolism KW - Repressor Proteins -- metabolism KW - Repressor Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67062995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=GalR+represses+galP1+by+inhibiting+the+rate-determining+open+complex+formation+through+RNA+polymerase+contact%3A+a+GalR+negative+control+mutant.&rft.au=Roy%2C+Siddhartha%3BSemsey%2C+Szabolcs%3BLiu%2C+Mofang%3BGussin%2C+Gary+N%3BAdhya%2C+Sankar&rft.aulast=Roy&rft.aufirst=Siddhartha&rft.date=2004-11-26&rft.volume=1&rft.issue=4&rft.spage=441&rft.isbn=&rft.btitle=&rft.title=Criminal+Justice%3A+International+Journal+of+Policy+and+Practice&rft.issn=14668025&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-22 N1 - Date created - 2004-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protection from cytosolic prion protein toxicity by modulation of protein translocation. AN - 67096580; 15526034 AB - Failure to promptly dispose of undesirable proteins is associated with numerous diseases. In the case of cellular prion protein (PrP), inhibition of the proteasome pathway can generate a highly aggregation-prone, cytotoxic form of PrP implicated in neurodegeneration. However, the predominant mechanisms that result in delivery of PrP, ordinarily targeted to the secretory pathway, to cytosolic proteasomes have been unclear. By accurately measuring the in vivo fidelity of protein translocation into the endoplasmic reticulum (ER), we reveal a slight inefficiency in PrP signal sequence function that generates proteasomally degraded cytosolic PrP. Attenuating this source of cytosolic PrP completely eliminates the dependence on proteasomes for PrP degradation. This allows cells to tolerate both higher expression levels and decreased proteasomal capacity without succumbing to the adverse consequences of misfolded PrP. Thus, the generation of potentially toxic cytosolic PrP is controlled primarily during its initial translocation into the ER. These results suggest that a substantial proportion of the cell's constitutive proteasomal burden may consist of proteins that, like PrP, fail to cotranslationally enter the secretory pathway with high fidelity. JF - The EMBO journal AU - Rane, Neena S AU - Yonkovich, Jesse L AU - Hegde, Ramanujan S AD - Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, MD 20892-5430, USA. Y1 - 2004/11/24/ PY - 2004 DA - 2004 Nov 24 SP - 4550 EP - 4559 VL - 23 IS - 23 SN - 0261-4189, 0261-4189 KW - PrPC Proteins KW - 0 KW - Protein Sorting Signals KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Cell Death -- physiology KW - Animals KW - Proteasome Endopeptidase Complex -- metabolism KW - Cells, Cultured KW - Protein Binding KW - Protein Transport KW - Endoplasmic Reticulum -- metabolism KW - PrPC Proteins -- biosynthesis KW - Cytosol -- metabolism KW - PrPC Proteins -- metabolism KW - Protein Folding UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67096580?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Protection+from+cytosolic+prion+protein+toxicity+by+modulation+of+protein+translocation.&rft.au=Rane%2C+Neena+S%3BYonkovich%2C+Jesse+L%3BHegde%2C+Ramanujan+S&rft.aulast=Rane&rft.aufirst=Neena&rft.date=2004-11-24&rft.volume=23&rft.issue=23&rft.spage=4550&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 - 2005-06-28 N1 - Date created - 2004-11-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Histol Histopathol. 2003 Apr;18(2):509-17 [12647802] Mol Biol Cell. 2005 Jan;16(1):279-91 [15496459] J Biol Chem. 2003 Jun 13;278(24):21732-43 [12663673] Trends Neurosci. 2003 Jul;26(7):337-9 [12850426] J Neurosci. 2003 Aug 6;23(18):7183-93 [12904479] Sci Aging Knowledge Environ. 2003 Aug 27;2003(34):RE6 [12944592] Annu Rev Neurosci. 2003;26:267-98 [12704221] J Biol Chem. 2003 Oct 17;278(42):40877-81 [12917444] Neuron. 2003 Oct 9;40(2):427-46 [14556719] J Cell Biol. 2003 Oct 27;163(2):257-69 [14581454] Science. 2003 Oct 31;302(5646):814-8 [14593165] Nature. 1999 Dec 16;402(6763):822-6 [10617204] EMBO J. 2000 Dec 15;19(24):6704-12 [11118205] J Biol Chem. 2001 Jan 19;276(3):2212-20 [11053411] Physiol Rev. 2001 Apr;81(2):741-66 [11274343] Mol Biol Cell. 2001 Apr;12(4):881-9 [11294893] N Engl J Med. 2001 May 17;344(20):1516-26 [11357156] Science. 2001 May 25;292(5521):1552-5 [11375494] Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7823-8 [11416167] J Biol Chem. 2001 Jul 13;276(28):26132-40 [11359769] Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8838-43 [11447277] EMBO J. 2001 Oct 1;20(19):5383-91 [11574470] Neurobiol Dis. 2001 Oct;8(5):743-63 [11592845] Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14955-60 [11742063] Dev Cell. 2002 Feb;2(2):207-17 [11832246] Mol Biol Cell. 2002 Nov;13(11):3775-86 [12429823] Science. 2002 Nov 29;298(5599):1785-8 [12386336] Science. 2002 Nov 29;298(5599):1781-5 [12386337] EMBO J. 2003 Feb 3;22(3):404-17 [12554642] Neurosignals. 2002 Sep-Oct;11(5):236-50 [12566925] Science. 2003 Oct 31;302(5646):871-4 [14593181] J Biol Chem. 2003 Nov 14;278(46):45960-8 [12933795] J Pathol. 2004 May;203(1):603-8 [15095484] J Cell Biol. 1988 Apr;106(4):1093-104 [3283145] J Virol. 1989 Dec;63(12):5238-43 [2585603] Cell. 1992 Oct 2;71(1):87-96 [1394433] EMBO J. 1994 Jun 1;13(11):2686-98 [8013467] Brain Pathol. 1995 Jan;5(1):53-9 [7767491] Nature. 1996 Jan 25;379(6563):339-43 [8552188] Neurology. 1996 Feb;46(2):532-7 [8614527] Annu Rev Biochem. 1996;65:271-303 [8811181] Science. 1998 Feb 6;279(5352):827-34 [9452375] Trends Cell Biol. 1999 Apr;9(4):132-7 [10203789] J Cell Biol. 2003 Apr 14;161(1):41-54 [12695498] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Role of Ventral Tegmental Area Glutamate in Contextual Cue-Induced Relapse to Heroin Seeking AN - 17594035; 6093317 AB - The environmental context previously associated with opiate use plays an important role in human relapse, but the neuronal mechanisms involved in context-induced drug relapse are not known. Using a rat relapse model, we determined the effect of a group II metabotropic glutamate receptor agonist [LY379268 ((-)-2-oxa-4-aminobicylco hexane-4,6-dicarboxylic acid)] on contextual cue-induced reinstatement of heroin seeking. LY379268, which acts centrally to reduce evoked glutamate release, was injected systemically or directly into the ventral tegmental area (VTA), a brain area involved in opiate reward and conditioned drug effects. Rats were trained to self-administer intravenous heroin for 12 d; drug infusions were paired with a discrete tone-light cue. Subsequently, lever pressing was extinguished in the presence of the discrete cue in a context that differed from the drug self-administration context in terms of visual, auditory, tactile, and circadian cues. After extinction of lever responding, LY379268 was injected systemically or into the VTA, and nonreinforced responding was determined in the extinction context or the drug context. Exposure to the heroin-associated context induced robust reinstatement of drug seeking, and this effect was attenuated by systemic or intra-VTA injections of LY379268. Results indicate that glutamate transmission in the VTA plays an important role in contextual cue-induced relapse to heroin seeking. JF - Journal of Neuroscience AU - Bossert, Jennifer M AU - Liu, Shirley Y AU - Lu, Lin AU - Shaham, Yavin AD - Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland Y1 - 2004/11/24/ PY - 2004 DA - 2004 Nov 24 SP - 10726 EP - 10730 PB - Society for Neuroscience, 11 Dupont Circle, N.W. Suite 500 Washington DC 20036 USA, [mailto:info@sfn.org], [URL:http://apu.sfn.org/] VL - 24 IS - 47 SN - 0270-6474, 0270-6474 KW - LY 379268 KW - rats KW - CSA Neurosciences Abstracts; Animal Behavior Abstracts; Toxicology Abstracts KW - Y 25807:Mammals (excluding primates) 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/17594035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neuroscience&rft.atitle=A+Role+of+Ventral+Tegmental+Area+Glutamate+in+Contextual+Cue-Induced+Relapse+to+Heroin+Seeking&rft.au=Bossert%2C+Jennifer+M%3BLiu%2C+Shirley+Y%3BLu%2C+Lin%3BShaham%2C+Yavin&rft.aulast=Bossert&rft.aufirst=Jennifer&rft.date=2004-11-24&rft.volume=24&rft.issue=47&rft.spage=10726&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-05-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Protein kinase C mediates phosphorylation, desensitization, and trafficking of the D2 dopamine receptor. AN - 67069157; 15347675 AB - Previously, D2 dopamine receptors (D2 DARs) have been shown to undergo G-protein-coupled receptor kinase phosphorylation in an agonist-specific fashion. We have now investigated the ability of the second messenger-activated protein kinases, protein kinase A (PKA) and protein kinase C (PKC), to mediate phosphorylation and desensitization of the D2 DAR. HEK293T cells were transiently transfected with the D2 DAR and then treated with intracellular activators and inhibitors of PKA or PKC. Treatment with agents that increase cAMP, and activate PKA, had no effect on the phosphorylation state of the D2 DAR, suggesting that PKA does not phosphorylate the D2 DAR in HEK293T cells. In contrast, cellular treatment with phorbol 12-myristate 13-acetate (PMA), a PKC activator, resulted in an approximately 3-fold increase in D2 DAR phosphorylation. The phosphorylation was specific for PKC as the PMA effect was mimicked by phorbol 12,13-dibutyrate, but not by 4alpha-phorbol 12,13-didecanoate, active and inactive, phorbol diesters, respectively. The PMA-mediated D2 DAR phosphorylation was completely blocked by co-treatment with the PKC inhibitor, bisindolylmaleimide II, and augmented by co-transfection with PKCbetaI. In contrast, PKC inhibition had no effect on agonist-promoted phosphorylation, suggesting that PKC is not involved in this response. PKC phosphorylation of the D2 DAR was found to promote receptor desensitization as reflected by a decrease in agonist potency for inhibiting cAMP accumulation. Most interestingly, PKC phosphorylation also promoted internalization of the D2 DAR through a beta-arrestin- and dynamin-dependent pathway, a response not usually associated with PKC phosphorylation of G-protein-coupled receptors. Site-directed mutagenesis experiments resulted in the identification of two domains of PKC phosphorylation sites within the third intracellular loop of the receptor. Both of these domains are involved in regulating sequestration of the D2 DAR, whereas only one domain is involved in receptor desensitization. These results indicate that PKC can mediate phosphorylation of the D2 DAR, resulting in both functional desensitization and receptor internalization. JF - The Journal of biological chemistry AU - Namkung, Yoon AU - Sibley, David R AD - Molecular Neuropharmacology Section, NINDS, National Institutes of Health, Bethesda, Maryland 20892-1406, USA. Y1 - 2004/11/19/ PY - 2004 DA - 2004 Nov 19 SP - 49533 EP - 49541 VL - 279 IS - 47 SN - 0021-9258, 0021-9258 KW - Protein Isoforms KW - 0 KW - Receptors, Dopamine D2 KW - Colforsin KW - 1F7A44V6OU KW - Cyclic AMP KW - E0399OZS9N KW - Protein Kinase C KW - EC 2.7.11.13 KW - GTP-Binding Protein alpha Subunits, Gq-G11 KW - EC 3.6.5.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Plasmids -- metabolism KW - Dose-Response Relationship, Drug KW - Enzyme Activation KW - Humans KW - GTP-Binding Protein alpha Subunits, Gq-G11 -- metabolism KW - Dopamine -- metabolism KW - Amino Acid Sequence KW - Binding Sites KW - Rats KW - Mutagenesis, Site-Directed KW - Colforsin -- pharmacology KW - Phosphorylation KW - Genes, Dominant KW - Transfection KW - Molecular Sequence Data KW - Cyclic AMP -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Membrane -- metabolism KW - Protein Structure, Tertiary KW - Mutation KW - Cell Line KW - Protein Transport KW - Protein Kinase C -- metabolism KW - Receptors, Dopamine D2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67069157?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Protein+kinase+C+mediates+phosphorylation%2C+desensitization%2C+and+trafficking+of+the+D2+dopamine+receptor.&rft.au=Namkung%2C+Yoon%3BSibley%2C+David+R&rft.aulast=Namkung&rft.aufirst=Yoon&rft.date=2004-11-19&rft.volume=279&rft.issue=47&rft.spage=49533&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 - 2005-01-11 N1 - Date created - 2004-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interleukin (IL)-15 and IL-2 reciprocally regulate expression of the chemokine receptor CX3CR1 through selective NFAT1- and NFAT2-dependent mechanisms. AN - 67066898; 15347678 AB - We have recently reported that interleukin (IL)-15 and IL-2, which signal through IL-2Rbetagamma, oppositely regulate expression of the proinflammatory chemokine receptor CX3CR1. Here we delineate molecular mechanisms responsible for this paradox. By using a luciferase reporter plasmid, we identified a 433-bp region spanning the major transcriptional start point of human CX3CR1 that, when expressed in human peripheral blood mononuclear cells (PBMCs), possessed strong constitutive promoter activity. IL-2 and IL-15 treatment increased and abolished this activity, respectively, mimicking their effects on endogenous CX3CR1. IL-2 and IL-15 have been reported to also have opposite effects on the immunoregulatory transcription factor NFAT (nuclear factor of activated T cells), and the 433-bp region contains a kappaB-like NFAT site. The effects of IL-15 and IL-2 on both CX3CR1 reporter activity and endogenous CX3CR1 transcription in PBMCs were abolished by the NFAT inhibitors cyclosporin A and VIVIT. Moreover, mutation of the kappaB-like NFAT sequence markedly attenuated IL-2 and IL-15 modulation of CX3CR1 promoter-reporter activity in PBMCs. Furthermore, chromatin immunoprecipitation revealed that IL-15 promoted specific recruitment of NFAT1 but not NFAT2 to the CX3CR1 promoter, whereas IL-2 had the converse effect. This appears to be relevant in vivo because mouse CX3CR1 mRNA was expressed in both PBMCs and splenocytes from NFAT1-/- mice injected with recombinant IL-15 but was undetectable in cells from IL-15-injected NFAT1+/+ BALB/c mice; as predicted, IL-2 up-regulated cx3cr1 in both mouse strains to a similar extent. Thus, by pharmacologic, genetic, and biochemical criteria in vitro and in vivo, our results suggest that IL-15 and IL-2 oppositely regulate CX3CR1 gene expression by differentially recruiting NFAT1 and NFAT2 to a kappaB-like NFAT site within the CX3CR1 promoter. We propose that expression of CX3CR1 and possibly other immunoregulatory genes may be determined in part by the balance of NFAT1 and NFAT2 activity in leukocytes. JF - The Journal of biological chemistry AU - Barlic, Jana AU - McDermott, David H AU - Merrell, Maya N AU - Gonzales, Jacqueline AU - Via, Laura E AU - Murphy, Philip M AD - Molecular Signaling Section, Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/11/19/ PY - 2004 DA - 2004 Nov 19 SP - 48520 EP - 48534 VL - 279 IS - 47 SN - 0021-9258, 0021-9258 KW - CX3CR1 protein, human KW - 0 KW - Chromatin KW - DNA-Binding Proteins KW - Interleukin-15 KW - Interleukin-2 KW - Membrane Proteins KW - NFATC Transcription Factors KW - NFATC1 protein, human KW - NFATC2 protein, human KW - Nfatc1 protein, mouse KW - Nfatc2 protein, mouse KW - Nuclear Proteins KW - Receptors, Chemokine KW - Recombinant Proteins KW - Transcription Factors KW - RNA KW - 63231-63-0 KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Animals KW - Chromatin -- metabolism KW - Humans KW - Open Reading Frames KW - Transcription, Genetic KW - Mice, Inbred BALB C KW - Mice, Transgenic KW - Mutagenesis KW - Promoter Regions, Genetic KW - RNA -- metabolism KW - Genes, Reporter KW - Chromatin Immunoprecipitation KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Time Factors KW - Plasmids -- metabolism KW - Exons KW - Dose-Response Relationship, Drug KW - Immunoprecipitation KW - Luciferases -- metabolism KW - Mice KW - Base Sequence KW - Transfection KW - Models, Genetic KW - Leukocytes, Mononuclear -- metabolism KW - Crosses, Genetic KW - Up-Regulation KW - Protein Structure, Tertiary KW - Mutation KW - Cell Line KW - Interleukin-2 -- metabolism KW - Transcription Factors -- metabolism KW - Membrane Proteins -- metabolism KW - Interleukin-15 -- physiology KW - Receptors, Chemokine -- metabolism KW - Gene Expression Regulation KW - Nuclear Proteins -- metabolism KW - Interleukin-2 -- physiology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67066898?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Law+and+Psychiatry&rft.atitle=The+influence+of+neighborhood+characteristics+on+police+officers%27+encounters+with+persons+suspected+to+have+a+serious+mental+illness&rft.au=Krishan%2C+Shaily%3BBakeman%2C+Roger%3BBroussard%2C+Beth%3BCristofaro%2C+Sarah+L.%3BHankerson-Dyson%2C+Dana%3BHusbands%2C+Letheshia%3BWatson%2C+Amy+C.%3BCompton%2C+Michael+T.&rft.aulast=Krishan&rft.aufirst=Shaily&rft.date=2014-07-01&rft.volume=37&rft.issue=4&rft.spage=359&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Law+and+Psychiatry&rft.issn=01602527&rft_id=info:doi/10.1016%2Fj.ijlp.2014.02.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-11 N1 - Date created - 2004-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Ga-dependent pathway that antagonizes multiple chemoattractant responses that regulate directional cell movement AN - 40037756; 3890033 AU - Brzostowski, JA AU - Parent, CA AU - Kimmel, A R Y1 - 2004/11/19/ PY - 2004 DA - 2004 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/40037756?accountid=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=Ga-dependent+pathway+that+antagonizes+multiple+chemoattractant+responses+that+regulate+directional+cell+movement&rft.au=Brzostowski%2C+JA%3BParent%2C+CA%3BKimmel%2C+A+R&rft.aulast=Brzostowski&rft.aufirst=JA&rft.date=2004-11-19&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 of Differentiation, P.O. Box 131854, Saint Paul, Minnesota 55113-1318, USA; phone: 651-659-9493; email: office@isdifferentiation.org; URL: www.isdifferentiation.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Identification of opioid receptor-ligand interactions using structurally related delta opioid receptor agonists and antagonists and molecular modeling AN - 39958875; 3890311 AU - Bryant, S D AU - Jinsmaa, Y AU - Lazarus, L H Y1 - 2004/11/19/ PY - 2004 DA - 2004 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39958875?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acpi&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=&rft.atitle=Identification+of+opioid+receptor-ligand+interactions+using+structurally+related+delta+opioid+receptor+agonists+and+antagonists+and+molecular+modeling&rft.au=Bryant%2C+S+D%3BJinsmaa%2C+Y%3BLazarus%2C+L+H&rft.aulast=Bryant&rft.aufirst=S&rft.date=2004-11-19&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: Kenes International, 17 rue de Cendrier, Geneva CH-1211, Switzerland; URL: www.kenes.com N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Regulation of Dictyostelium discoideum chemotaxis, the role of tumor suppressor TSC2 AN - 39925875; 3891838 AU - Rosel, D AU - Kimmel, A R Y1 - 2004/11/19/ PY - 2004 DA - 2004 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39925875?accountid=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+Dictyostelium+discoideum+chemotaxis%2C+the+role+of+tumor+suppressor+TSC2&rft.au=Rosel%2C+D%3BKimmel%2C+A+R&rft.aulast=Rosel&rft.aufirst=D&rft.date=2004-11-19&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 of Differentiation, P.O. Box 131854, Saint Paul, Minnesota 55113-1318, USA; phone: 651-659-9493; email: office@isdifferentiation.org; URL: www.isdifferentiation.org N1 - Last updated - 2010-05-03 ER - TY - CPAPER T1 - Partner-dependent interaction of IRF8 with chromatin visualized in live differentiating macrophages AN - 39849856; 3891420 AU - Robbio, L L AU - Tamura, T AU - Remoli, A AU - Karpova, T AU - McNally, J AU - Ozato, K Y1 - 2004/11/19/ PY - 2004 DA - 2004 Nov 19 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39849856?accountid=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=Partner-dependent+interaction+of+IRF8+with+chromatin+visualized+in+live+differentiating+macrophages&rft.au=Robbio%2C+L+L%3BTamura%2C+T%3BRemoli%2C+A%3BKarpova%2C+T%3BMcNally%2C+J%3BOzato%2C+K&rft.aulast=Robbio&rft.aufirst=L&rft.date=2004-11-19&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 of Differentiation, P.O. Box 131854, Saint Paul, Minnesota 55113-1318, USA; phone: 651-659-9493; email: office@isdifferentiation.org; URL: www.isdifferentiation.org N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Neurodevelopmental and Growth Impairment Among Extremely Low-Birth-Weight Infants With Neonatal Infection AN - 211314526; 15547163 AB - Stoll et al aim to determine if neonatal infections in extremely low-birth-weight (ELBW) infants are associated with increased risks of adverse neurodevelopmental and growth sequelae in early childhood. This large cohort study suggests that neonatal infections among ELBW infants are associated with poor neurodevelopmental and growth outcomes in early childhood. Additional studies are needed to elucidate the pathogenesis of brain injury in infants with infection so that novel interventions to improve these outcomes can be explored. JF - JAMA AU - Stoll, Barbara J AU - Hansen, Nellie I AU - Adams-Chapman, Ira AU - Fanaroff, Avroy A AU - et al Y1 - 2004/11/17/ PY - 2004 DA - 2004 Nov 17 SP - 2357 EP - 65 CY - Chicago PB - American Medical Association VL - 292 IS - 19 SN - 00987484 KW - Meetings And Congresses KW - Babies KW - Birth weight KW - Critical care KW - Child development KW - Brain damage KW - /article.aspx?articleid=199811 KW - Enterocolitis, Necrotizing -- complications KW - Humans KW - Infant, Newborn KW - Meningitis -- complications KW - Cerebral Palsy -- etiology KW - Infant KW - Growth KW - Vision Disorders -- etiology KW - Hearing Loss -- epidemiology KW - Cohort Studies KW - Developmental Disabilities -- epidemiology KW - Cerebral Palsy -- epidemiology KW - Hearing Loss -- etiology KW - Male KW - Infection -- complications KW - Female KW - Vision Disorders -- epidemiology KW - Developmental Disabilities -- etiology KW - Sepsis -- complications KW - Infant, Premature, Diseases KW - Infant, Very Low Birth Weight -- growth & development UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/211314526?accountid=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=JAMA&rft.atitle=Neurodevelopmental+and+Growth+Impairment+Among+Extremely+Low-Birth-Weight+Infants+With+Neonatal+Infection%3A+The+Journal+of+the+American+Medical+Association+The+Journal+of+the+American+Medical+Association&rft.au=Stoll%2C+Barbara+J%3BHansen%2C+Nellie+I%3BAdams-Chapman%2C+Ira%3BFanaroff%2C+Avroy+A%3Bet+al&rft.aulast=Stoll&rft.aufirst=Barbara&rft.date=2004-11-17&rft.volume=292&rft.issue=19&rft.spage=2357&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Central N1 - Copyright - Copyright American Medical Association Nov 17, 2004 N1 - Document feature - Tables; References N1 - Last updated - 2016-12-07 N1 - CODEN - JAMAAP ER - TY - JOUR T1 - Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation. AN - 67142210; 15570005 AB - Permeability of tumor vasculature can be a major barrier to successful drug delivery, particularly for high molecular weight agents such as monoclonal antibodies and their diagnostic or therapeutic conjugates. In this study, changes in permeability of SCCVII tumor vessels after radiation treatment were evaluated by dynamic magnetic resonance imaging as a function of time after irradiation using a generation-8 polyamidoamine dendrimer (G8-Gd-D)-based magnetic resonance imaging contrast agent shown previously to be confined to tumor blood vessels. Tumor irradiation consisted of either single doses (2-15 Gy) or various daily fractionated doses (5 days). A single radiation dose of 15 Gy resulted in significant transient image enhancement of the tumor tissue with a maximum occurring between 7 and 24 hours after radiation treatment. No observable enhancement was recorded for fractionated radiation doses. Use of dynamic magnetic resonance imaging coupled with G8-Gd-D provides an exquisite methodology capable of defining the timing of enhanced permeability of macromolecules in tumors after irradiation. Such information might be applied to optimize the efficacy of subsequent or concurrent therapies including radiolabeled antibodies or other anticancer agents in combination with external beam therapies. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Kobayashi, Hisataka AU - Reijnders, Koen AU - English, Sean AU - Yordanov, Alexander T AU - Milenic, Diane E AU - Sowers, Anastasia L AU - Citrin, Deborah AU - Krishna, Murali C AU - Waldmann, Thomas A AU - Mitchell, James B AU - Brechbiel, Martin W AD - Metabolism Branch, Radiation Biology Branch, and Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1002, USA. kobayash@mail.nih.gov Y1 - 2004/11/15/ PY - 2004 DA - 2004 Nov 15 SP - 7712 EP - 7720 VL - 10 IS - 22 SN - 1078-0432, 1078-0432 KW - Amines KW - 0 KW - Antibodies, Monoclonal KW - Antineoplastic Agents KW - Contrast Media KW - Macromolecular Substances KW - Nylons KW - Index Medicus KW - Neoplasm Transplantation KW - Magnetic Resonance Imaging KW - Animals KW - Mice, Inbred C3H KW - Mice KW - Antibodies, Monoclonal -- chemistry KW - Antineoplastic Agents -- therapeutic use KW - Time Factors KW - Image Processing, Computer-Assisted KW - Female KW - Nylons -- chemistry KW - Neoplasms -- blood supply KW - Neoplasms, Radiation-Induced -- pathology KW - Amines -- pharmacology KW - Nylons -- pharmacology KW - Amines -- chemistry KW - Neovascularization, Pathologic KW - Contrast Media -- pharmacology KW - Macromolecular Substances -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67142210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Application+of+a+macromolecular+contrast+agent+for+detection+of+alterations+of+tumor+vessel+permeability+induced+by+radiation.&rft.au=Kobayashi%2C+Hisataka%3BReijnders%2C+Koen%3BEnglish%2C+Sean%3BYordanov%2C+Alexander+T%3BMilenic%2C+Diane+E%3BSowers%2C+Anastasia+L%3BCitrin%2C+Deborah%3BKrishna%2C+Murali+C%3BWaldmann%2C+Thomas+A%3BMitchell%2C+James+B%3BBrechbiel%2C+Martin+W&rft.aulast=Kobayashi&rft.aufirst=Hisataka&rft.date=2004-11-15&rft.volume=10&rft.issue=22&rft.spage=7712&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 - 2005-05-17 N1 - Date created - 2004-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Infectivity studies of both ash and air emissions from simulated incineration of scrapie-contaminated tissues. AN - 67136119; 15575075 AB - We investigated the effectiveness of 15 min exposures to 600 and 1000 degrees C in continuous flow normal and starved-air incineration-like conditions to inactivate samples of pooled brain macerates from hamsters infected with the 263K strain of hamster-adapted scrapie with an infectivity titer in excess of 10(9) mean lethal doses (LD50) per g. Bioassays of the ash, outflow tubing residues, and vented emissions from heating 1 g of tissue samples yielded a total of two transmissions among 21 inoculated animals from the ash of a single specimen burned in normal air at 600 degrees C. No other ash, residue, or emission from samples heated at either 600 or 1000 degrees C, under either normal or starved-air conditions, transmitted disease. We conclude that at temperatures approaching 1000 degrees C under the air conditions and combustion times used in these experiments, contaminated tissues can be completely inactivated, with no release of infectivity into the environment from emissions. The extent to which this result can be realized in actual incinerators and other combustion devices will depend on equipment design and operating conditions during the heating process. JF - Environmental science & technology AU - Brown, Paul AU - Rau, Edward H AU - Lemieux, Paul AU - Johnson, Bruce K AU - Bacote, Alfred E AU - Gajdusek, D Carleton AD - Laboratory of CNS Studies, National Institute of Neurological Disorders and Stroke, and Div. of Environmental Protection, Office of Research Facilities Development and Operations, NIH, US Dept. of HHS, Bethesda, MD 20892, USA. paulwbrown@comcast.net Y1 - 2004/11/15/ PY - 2004 DA - 2004 Nov 15 SP - 6155 EP - 6160 VL - 38 IS - 22 SN - 0013-936X, 0013-936X KW - Air Pollutants KW - 0 KW - PrPSc Proteins KW - Index Medicus KW - Animals KW - Brain -- metabolism KW - Time Factors KW - Cricetinae KW - PrPSc Proteins -- pathogenicity KW - Hot Temperature KW - Scrapie -- transmission KW - Incineration -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67136119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+science+%26+technology&rft.atitle=Infectivity+studies+of+both+ash+and+air+emissions+from+simulated+incineration+of+scrapie-contaminated+tissues.&rft.au=Brown%2C+Paul%3BRau%2C+Edward+H%3BLemieux%2C+Paul%3BJohnson%2C+Bruce+K%3BBacote%2C+Alfred+E%3BGajdusek%2C+D+Carleton&rft.aulast=Brown&rft.aufirst=Paul&rft.date=2004-11-15&rft.volume=38&rft.issue=22&rft.spage=6155&rft.isbn=&rft.btitle=&rft.title=Environmental+science+%26+technology&rft.issn=0013936X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-06-16 N1 - Date created - 2004-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol use disorders and mood disorders: a National Institute on Alcohol Abuse and Alcoholism perspective. AN - 67093184; 15556112 JF - Biological psychiatry AU - Li, Ting-Kai AU - Hewitt, Brenda G AU - Grant, Bridget F AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, U.S. Department of Health and Human Services, 5635 Fishers Lane, Room 2000, Bethesda, MD 20892-9304, USA. Y1 - 2004/11/15/ PY - 2004 DA - 2004 Nov 15 SP - 718 EP - 720 VL - 56 IS - 10 SN - 0006-3223, 0006-3223 KW - Index Medicus KW - Models, Psychological KW - Humans KW - National Institutes of Health (U.S.) KW - Adult KW - Child KW - Research KW - Adolescent KW - United States -- epidemiology KW - Research Design KW - Comorbidity KW - Risk Assessment KW - Alcoholism -- epidemiology KW - Mood Disorders -- complications KW - Mood Disorders -- epidemiology KW - Alcoholism -- genetics KW - Alcoholism -- complications KW - Mood Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67093184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alcohol+use+disorders+and+mood+disorders%3A+a+National+Institute+on+Alcohol+Abuse+and+Alcoholism+perspective.&rft.au=Li%2C+Ting-Kai%3BHewitt%2C+Brenda+G%3BGrant%2C+Bridget+F&rft.aulast=Li&rft.aufirst=Ting-Kai&rft.date=2004-11-15&rft.volume=56&rft.issue=10&rft.spage=718&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 - 2005-01-11 N1 - Date created - 2004-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The reality of comorbidity: depression and drug abuse. AN - 67093160; 15556111 JF - Biological psychiatry AU - Volkow, Nora D AD - National Institute on Drug Abuse, 6001 Executive Boulevard, Suite 5274, Bethesda, MD 20892, USA. Y1 - 2004/11/15/ PY - 2004 DA - 2004 Nov 15 SP - 714 EP - 717 VL - 56 IS - 10 SN - 0006-3223, 0006-3223 KW - Index Medicus KW - Environment KW - Health Services KW - Humans KW - Mood Disorders -- therapy KW - Research KW - Mood Disorders -- epidemiology KW - Adolescent KW - Mood Disorders -- psychology KW - Mood Disorders -- genetics KW - Comorbidity KW - Depressive Disorder -- epidemiology KW - Substance-Related Disorders -- therapy KW - Depressive Disorder -- psychology KW - Depressive Disorder -- genetics KW - Substance-Related Disorders -- psychology KW - Depressive Disorder -- therapy KW - Substance-Related Disorders -- genetics KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67093160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+reality+of+comorbidity%3A+depression+and+drug+abuse.&rft.au=Volkow%2C+Nora+D&rft.aulast=Volkow&rft.aufirst=Nora&rft.date=2004-11-15&rft.volume=56&rft.issue=10&rft.spage=714&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 - 2005-01-11 N1 - Date created - 2004-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The conundrum of co-occurring mental and substance use disorders: opportunities for research. AN - 67092015; 15556114 JF - Biological psychiatry AU - Gonzales, Junius J AU - Insel, Thomas R AD - National Institute of Mental Health, 6001 Executive Boulevard, Room 8235, Bethesda, MD 20892, USA. Y1 - 2004/11/15/ PY - 2004 DA - 2004 Nov 15 SP - 723 EP - 725 VL - 56 IS - 10 SN - 0006-3223, 0006-3223 KW - Index Medicus KW - Health Services KW - Humans KW - Prognosis KW - Research KW - United States -- epidemiology KW - Health Services Accessibility KW - Comorbidity KW - Substance-Related Disorders -- physiopathology KW - Substance-Related Disorders -- therapy KW - Mental Disorders -- therapy KW - Mental Disorders -- epidemiology KW - Substance-Related Disorders -- epidemiology KW - Mental Disorders -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67092015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=The+conundrum+of+co-occurring+mental+and+substance+use+disorders%3A+opportunities+for+research.&rft.au=Gonzales%2C+Junius+J%3BInsel%2C+Thomas+R&rft.aulast=Gonzales&rft.aufirst=Junius&rft.date=2004-11-15&rft.volume=56&rft.issue=10&rft.spage=723&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 - 2005-01-11 N1 - Date created - 2004-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elevated serum-soluble interleukin-2 receptor levels in patients with anaplastic large cell lymphoma. AN - 67041498; 15205267 AB - Levels of serum soluble interleukin 2 receptor (sIL-2R) provide a reliable marker of disease activity in patients with hairy cell leukemia and adult T-cell leukemia/lymphoma. The malignant cells in patients with anaplastic large cell lymphoma (ALCL) express CD30 and are usually positive for expression of CD25. We measured serum sIL-2R and soluble CD30 (sCD30) levels in patients with ALCL treated with EPOCH (etoposide, prednisone, Oncovin, Cytoxan, hydroxydaunorubicin) infusional chemotherapy. Serum sCD30 levels were elevated and decreased in response to therapy as previously reported. Serum sIL-2R levels were elevated in 7 of 9 patients with ALCL and decreased in response to treatment. Baseline serum sIL-2R levels varied but correlated well with serum sCD30 levels (r = 0.97). Patients positive for the anaplastic lymphoma kinase (ALK) gene showed elevated sIL-2R levels, whereas those negative for ALK had normal serum sIL-2R levels and their tumors lacked CD25 expression. Serum sIL-2R levels were elevated in both patients with recurrent disease. JF - Blood AU - Janik, John E AU - Morris, John C AU - Pittaluga, Stefania AU - McDonald, Kristin AU - Raffeld, Mark AU - Jaffe, Elaine S AU - Grant, Nicole AU - Gutierrez, Martin AU - Waldmann, Thomas A AU - Wilson, Wyndham H AD - Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. janikj@mail.nih.gov. Y1 - 2004/11/15/ PY - 2004 DA - 2004 Nov 15 SP - 3355 EP - 3357 VL - 104 IS - 10 SN - 0006-4971, 0006-4971 KW - Antigens, CD30 KW - 0 KW - Biomarkers, Tumor KW - Receptors, Interleukin-2 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Abridged Index Medicus KW - Index Medicus KW - Antigens, CD30 -- blood KW - Solubility KW - Humans KW - Prednisone -- therapeutic use KW - Etoposide -- therapeutic use KW - Aged KW - Recurrence KW - Cyclophosphamide -- therapeutic use KW - Vincristine -- therapeutic use KW - Adult KW - Doxorubicin -- therapeutic use KW - Middle Aged KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Female KW - Male KW - Receptors, Interleukin-2 -- blood KW - Lymphoma, Large B-Cell, Diffuse -- drug therapy KW - Lymphoma, Large B-Cell, Diffuse -- blood KW - Lymphoma, Large B-Cell, Diffuse -- immunology KW - Biomarkers, Tumor -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67041498?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Elevated+serum-soluble+interleukin-2+receptor+levels+in+patients+with+anaplastic+large+cell+lymphoma.&rft.au=Janik%2C+John+E%3BMorris%2C+John+C%3BPittaluga%2C+Stefania%3BMcDonald%2C+Kristin%3BRaffeld%2C+Mark%3BJaffe%2C+Elaine+S%3BGrant%2C+Nicole%3BGutierrez%2C+Martin%3BWaldmann%2C+Thomas+A%3BWilson%2C+Wyndham+H&rft.aulast=Janik&rft.aufirst=John&rft.date=2004-11-15&rft.volume=104&rft.issue=10&rft.spage=3355&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-23 N1 - Date created - 2004-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel Identification of a Sulfur-Centered, Radical-Derived 5,5-Dimethyl-1-pyrroline N-Oxide Nitrone Adduct Formed from the Oxidation of DTT by LC/ELISA, LC/Electrospray Ionization-MS, and LC/Tandem MS AN - 17736612; 6091501 AB - The detection of highly reactive free radicals generated in biological systems by an ESR spin-trapping technique is always difficult and limited due to the short lifetimes of ESR active spin-trapping radical adducts and poor structural information provided by ESR spectra. In this investigation, we have for the first time employed anti-5,5-dimethyl-1-pyrroline N-oxide (DMPO) polyclonal antiserum that specifically recognizes stable, ESR silent end products of DMPO radical adducts and combined HPLC with ELISA, electrospray ionization mass spectrometry (ESI-MS), and tandem mass spectrometry (MS/MS) to separate and characterize DMPO nitrone adducts derived from free radical metabolites. When mircoperoxidase-11 (MP-11) reacted with DTT in the presence of DMPO with or without H sub(2)O sub(2), we detected radical-derived DMPO nitrone adducts by ELISA. Similar results were obtained when MP-11 was replaced by hemin. To identify the DMPO nitrone adducts formed in both reaction systems, LC separation was carried out, and the fractions eluted from the LC column were collected and analyzed by ELISA. In both reaction mixtures, we found that only one peak with the same retention time showed a strong positive ELISA signal, suggesting that this peak was from radical-derived DMPO nitrone adducts and that both systems produced the same free radical metabolites. Using online LC/ESI-MS, LC/MS/MS, and super(1)H NMR, we demonstrated that the DMPO nitrone adducts formed are from the DMPO adducts of the sulfur-centered radical of DTT. The successful application of LC/ELISA, LC/MS, and LC/MS/MS in this study makes it possible to separate and identify the stable DMPO nitrone adducts derived from free radical metabolites generated in biological systems. JF - Chemical Research in Toxicology AU - Guo, Q AU - Gao, G AU - Qian, SY AU - Mason, R P AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA Y1 - 2004/11/15/ PY - 2004 DA - 2004 Nov 15 SP - 1481 EP - 1490 VL - 17 IS - 11 SN - 0893-228X, 0893-228X KW - Toxicology Abstracts KW - High-performance liquid chromatography KW - Enzyme-linked immunosorbent assay KW - Adducts KW - Free radicals KW - N-Oxides KW - Metabolites KW - Hemin KW - Spectrometry KW - Hydrogen peroxide KW - Oxidation KW - N.M.R. KW - Ionization KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17736612?accountid=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=Novel+Identification+of+a+Sulfur-Centered%2C+Radical-Derived+5%2C5-Dimethyl-1-pyrroline+N-Oxide+Nitrone+Adduct+Formed+from+the+Oxidation+of+DTT+by+LC%2FELISA%2C+LC%2FElectrospray+Ionization-MS%2C+and+LC%2FTandem+MS&rft.au=Guo%2C+Q%3BGao%2C+G%3BQian%2C+SY%3BMason%2C+R+P&rft.aulast=Guo&rft.aufirst=Q&rft.date=2004-11-15&rft.volume=17&rft.issue=11&rft.spage=1481&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/10.1021%2Ftx049837o LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - High-performance liquid chromatography; Enzyme-linked immunosorbent assay; Hydrogen peroxide; Free radicals; Adducts; Oxidation; N-Oxides; Hemin; N.M.R.; Metabolites; Ionization; Spectrometry DO - http://dx.doi.org/10.1021/tx049837o ER - TY - JOUR T1 - Trastuzumab Down-Regulates Bcl-2 Expression and Potentiates Apoptosis Induction by Bcl-2/Bcl-X sub(L) Bispecific Antisense Oligonucleotides in HER- 2Gene-Amplified Breast Cancer Cells AN - 17300780; 6092621 AB - PURPOSE: To investigate the possible existence of an antiapoptotic cross- talk between HER-2 and antiapoptotic Bcl-2 family members. Experimental Design: Bcl-2 and Bcl-X sub(L) expression and apoptosis induction were analyzed in HER- 2gene-amplified (BT474) and nonamplified (ZR 75-1) breast cancer cell lines exposed to trastuzumab, alone or in combination with either Bcl-2/Bcl-X sub(L) bispecific antisense oligonucleotides (AS-4625) or the small-molecule Bcl-2 antagonist HA14-1. RESULTS: In addition to HER-2 and epidermal growth factor receptor, trastuzumab down-regulated Bcl-2, but not Bcl-X sub(L), protein, and mRNA expression in BT474 cells. Interestingly, trastuzumab-induced down- regulation of HER-2 and Bcl-2 was also observed in three of five and two of three breast cancer patients undergoing trastuzumab treatment, respectively. Despite Bcl-2 down-regulation, however, trastuzumab only marginally increased the rate of apoptosis (7.3 +/- 3.5%). We therefore investigated whether a combination of AS-4625 and trastuzumab might increase proapoptotic efficiency. AS-4625 treatment of BT474 cells decreased both Bcl-2 and Bcl-X sub(L) expression, resulting in a 21 +/- 7% net apoptosis induction; the combination of AS-4625 followed by trastuzumab resulted in a significantly stronger induction of apoptosis (37 +/- 6%, P < 0.01) that was not observed with the reverse treatment sequence (trastuzumab followed by AS-4625). Similar results were obtained with the Bcl-2 antagonist HA14-1; indeed, exposure of BT474 cells to HA14-1 followed by trastuzumab resulted in a striking proapoptotic synergism (combination index = 0.58 +/- 0.18), as assessed by isobologram analysis. CONCLUSIONS: Altogether our findings suggest that combined targeting of HER-2 and Bcl-2 may represent a novel, rational approach to more effective breast cancer therapy. JF - Clinical Cancer Research AU - Milella, Michele AU - Trisciuoglio, Daniela AU - Bruno, Tiziana AU - Ciuffreda, Ludovica AU - Mottolese, Marcella AU - Cianciulli, Anna AU - Cognetti, Francesco AU - Zangemeister-Wittke, Uwe AU - Del Bufalo, Donatella AU - Zupi, Gabriella AD - Division of Medical Oncology A, Laboratory of Experimental Preclinical Chemotherapy, Laboratory B, Division of Pathology, and Division of Clinical Pathology, Regina Elena National Cancer Institute, Rome, Italy Y1 - 2004/11/15/ PY - 2004 DA - 2004 Nov 15 SP - 7747 EP - 7756 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 10 IS - 22 SN - 1078-0432, 1078-0432 KW - Oncogenes & Growth Factors Abstracts; Biotechnology and Bioengineering Abstracts KW - W 30915:Pharmaceuticals & Vaccines KW - B 26640:Cell Cycle & DNA Repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17300780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Cancer+Research&rft.atitle=Trastuzumab+Down-Regulates+Bcl-2+Expression+and+Potentiates+Apoptosis+Induction+by+Bcl-2%2FBcl-X+sub%28L%29+Bispecific+Antisense+Oligonucleotides+in+HER-+2Gene-Amplified+Breast+Cancer+Cells&rft.au=Milella%2C+Michele%3BTrisciuoglio%2C+Daniela%3BBruno%2C+Tiziana%3BCiuffreda%2C+Ludovica%3BMottolese%2C+Marcella%3BCianciulli%2C+Anna%3BCognetti%2C+Francesco%3BZangemeister-Wittke%2C+Uwe%3BDel+Bufalo%2C+Donatella%3BZupi%2C+Gabriella&rft.aulast=Milella&rft.aufirst=Michele&rft.date=2004-11-15&rft.volume=10&rft.issue=22&rft.spage=7747&rft.isbn=&rft.btitle=&rft.title=Clinical+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - AMP-activated protein kinase-regulated phosphorylation and acetylation of importin alpha1: involvement in the nuclear import of RNA-binding protein HuR. AN - 67056936; 15342649 AB - Nuclear import of HuR, a shuttling RNA-binding protein, is associated with reduced stability of its target mRNAs. Increased function of the AMP-activated protein kinase (AMPK), an enzyme involved in responding to metabolic stress, was recently shown to reduce the cytoplasmic levels of HuR. Here, we provide evidence that importin alpha1, an adaptor protein involved in nuclear import, contributes to the nuclear import of HuR through two AMPK-modulated mechanisms. First, AMPK triggered the acetylation of importin alpha1 on Lys(22), a process dependent on the acetylase activity of p300. Second, AMPK phosphorylated importin alpha1 on Ser(105). Accordingly, expression of importin alpha1 proteins bearing K22R or S105A mutations failed to mediate the nuclear import of HuR in intact cells. Our results point to importin alpha1 as a critical downstream target of AMPK and key mediator of AMPK-triggered HuR nuclear import. JF - The Journal of biological chemistry AU - Wang, Wengong AU - Yang, Xiaoling AU - Kawai, Tomoko AU - López de Silanes, Isabel AU - Mazan-Mamczarz, Krystyna AU - Chen, Peili AU - Chook, Yuh Min AU - Quensel, Christina AU - Köhler, Matthias AU - Gorospe, Myriam AD - Laboratory of Cellular and Molecular Biology, NIA Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2004/11/12/ PY - 2004 DA - 2004 Nov 12 SP - 48376 EP - 48388 VL - 279 IS - 46 SN - 0021-9258, 0021-9258 KW - Antigens, Surface KW - 0 KW - ELAV Proteins KW - ELAV-Like Protein 1 KW - ELAVL1 protein, human KW - Histone Deacetylase Inhibitors KW - Multienzyme Complexes KW - Nuclear Proteins KW - RNA, Messenger KW - RNA-Binding Proteins KW - Recombinant Fusion Proteins KW - Ribonucleotides KW - Trans-Activators KW - alpha Karyopherins KW - karyopherin alpha 2 KW - Aminoimidazole Carboxamide KW - 360-97-4 KW - Serine KW - 452VLY9402 KW - AMP-Activated Protein Kinases KW - EC 2.7.11.1 KW - PRKAA1 protein, human KW - Protein-Serine-Threonine Kinases KW - Histone Deacetylases KW - EC 3.5.1.98 KW - AICA ribonucleotide KW - F0X88YW0YK KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Trans-Activators -- metabolism KW - Nuclear Proteins -- genetics KW - Enzyme Activation KW - Humans KW - RNA Stability KW - Serine -- metabolism KW - Lysine -- metabolism KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Acetylation KW - RNA, Messenger -- metabolism KW - Phosphorylation KW - Trans-Activators -- genetics KW - Ribonucleotides -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Histone Deacetylases -- metabolism KW - Nuclear Proteins -- metabolism KW - Cell Line KW - alpha Karyopherins -- metabolism KW - Multienzyme Complexes -- metabolism KW - Aminoimidazole Carboxamide -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - RNA-Binding Proteins -- metabolism KW - Active Transport, Cell Nucleus -- physiology KW - Aminoimidazole Carboxamide -- analogs & derivatives KW - Protein-Serine-Threonine Kinases -- genetics KW - Antigens, Surface -- metabolism KW - alpha Karyopherins -- genetics KW - Multienzyme Complexes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67056936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=AMP-activated+protein+kinase-regulated+phosphorylation+and+acetylation+of+importin+alpha1%3A+involvement+in+the+nuclear+import+of+RNA-binding+protein+HuR.&rft.au=Wang%2C+Wengong%3BYang%2C+Xiaoling%3BKawai%2C+Tomoko%3BL%C3%B3pez+de+Silanes%2C+Isabel%3BMazan-Mamczarz%2C+Krystyna%3BChen%2C+Peili%3BChook%2C+Yuh+Min%3BQuensel%2C+Christina%3BK%C3%B6hler%2C+Matthias%3BGorospe%2C+Myriam&rft.aulast=Wang&rft.aufirst=Wengong&rft.date=2004-11-12&rft.volume=279&rft.issue=46&rft.spage=48376&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 - 2005-01-21 N1 - Date created - 2004-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor cells resistant to a microtubule-depolymerizing hemiasterlin analogue, HTI-286, have mutations in alpha- or beta-tubulin and increased microtubule stability. AN - 67028611; 15518543 AB - Hemiasterlins are sponge-derived tripeptides that inhibit cell growth by depolymerizing existing microtubules and inhibiting microtubule assembly. Since hemiasterlins are poor substrates for P-glycoprotein, they are attractive candidates for cancer therapy and have been undergoing clinical trials. The basis of resistance to a synthetic analogue of hemiasterlin, HTI-286 (HTI), was examined in cell populations derived from ovarian carcinoma (A2780/1A9) cells selected in HTI-286. 1A9-HTI-resistant cells (1A9-HTI(R) series) were 57-89-fold resistant to HTI. Cross-resistance (3-186-fold) was observed to other tubulin depolymerizing drugs, with collateral sensitivity (2-14-fold) to tubulin polymerizing agents. Evaluation of the percentage of polymerized and soluble tubulin in 1A9 parental and 1A9-HTI(R) cells corroborated the HTI cytotoxicity data. At 22 degrees C or 37 degrees C, in the absence of any drug, the percentage of polymerized microtubules for each of the 1A9-HTI(R) populations was greater than that in the 1A9 parental cells, consistent with more stable microtubules. Furthermore, microtubules in the 1A9-HTI(R) populations were also more resistant to depolymerization at 4 degrees C and had more acetylated and detyrosinated (Glu-tubulin) alpha-tubulin, all characteristic of more stable microtubules. The 1A9-HTI(R) cell populations exhibited either a single nucleotide change in the M40 beta-tubulin isotype, S172A, or in two cell populations where no beta-tubulin mutation was detected, mutations in the Kalpha-1 alpha-tubulin isotype, S165P and R221H in one resistant cell population and I384V in another. Unlike reports of mutations resulting in reduced drug affinity, the experimental data and location of mutations are consistent with resistance to HTI-286 mediated by microtubule-stabilizing mutations in beta- or alpha-tubulin. JF - Biochemistry AU - Poruchynsky, Marianne S AU - Kim, Jong-Hyeok AU - Nogales, Eva AU - Annable, Tami AU - Loganzo, Frank AU - Greenberger, Lee M AU - Sackett, Dan L AU - Fojo, Tito AD - Cancer Therapeutics Branch, The NCI Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. mporuch@helix.nih.gov Y1 - 2004/11/09/ PY - 2004 DA - 2004 Nov 09 SP - 13944 EP - 13954 VL - 43 IS - 44 SN - 0006-2960, 0006-2960 KW - Growth Inhibitors KW - 0 KW - HTI-286 KW - Oligopeptides KW - Tubulin KW - hemiasterlin KW - Tyrosine KW - 42HK56048U KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Ovarian Neoplasms -- metabolism KW - Ovarian Neoplasms -- genetics KW - Dimerization KW - Humans KW - Cell Line, Tumor KW - Cold Temperature KW - Paclitaxel -- pharmacology KW - Acetylation KW - Protein Structure, Tertiary -- genetics KW - Ovarian Neoplasms -- pathology KW - Tyrosine -- metabolism KW - Protein Structure, Secondary -- genetics KW - Female KW - Tubulin -- chemistry KW - Microtubules -- metabolism KW - Growth Inhibitors -- pharmacology KW - Tubulin -- genetics KW - Tubulin -- metabolism KW - Oligopeptides -- pharmacology KW - Drug Resistance, Neoplasm KW - Microtubules -- drug effects KW - Microtubules -- genetics KW - Oligopeptides -- toxicity KW - Mutation KW - Growth Inhibitors -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67028611?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Tumor+cells+resistant+to+a+microtubule-depolymerizing+hemiasterlin+analogue%2C+HTI-286%2C+have+mutations+in+alpha-+or+beta-tubulin+and+increased+microtubule+stability.&rft.au=Poruchynsky%2C+Marianne+S%3BKim%2C+Jong-Hyeok%3BNogales%2C+Eva%3BAnnable%2C+Tami%3BLoganzo%2C+Frank%3BGreenberger%2C+Lee+M%3BSackett%2C+Dan+L%3BFojo%2C+Tito&rft.aulast=Poruchynsky&rft.aufirst=Marianne&rft.date=2004-11-09&rft.volume=43&rft.issue=44&rft.spage=13944&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-11 N1 - Date created - 2004-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A method for cloning and sequencing long palindromic DNA junctions. AN - 67063285; 15534362 AB - DNA sequences containing long adjacent inverted repeats (palindromes) are inherently unstable and are associated with many types of chromosomal rearrangements. The instability associated with palindromic sequences also creates difficulties in their molecular analysis: long palindromes (>250 bp/arm) are highly unstable in Escherichia coli, and cannot be directly PCR amplified or sequenced due to their propensity to form intra-strand hairpins. Here, we show that DNA molecules containing long palindromes (>900 bp/arm) can be transformed and stably maintained in Saccharomyces cerevisiae cells lacking a functional SAE2 gene. Treatment of the palindrome-containing DNA with sodium bisulfite at high temperature results in deamination of cytosine, converting it to uracil and thus reducing the propensity to form intra-strand hairpins. The bisulfite-treated DNA can then be PCR amplified, cloned and sequenced, allowing determination of the nucleotide sequence of the junctions. Our data demonstrates that long palindromes with either no spacer (perfect) or a 2 bp spacer can be stably maintained, recovered and sequenced from sae2Delta yeast cells. Since DNA sequences from mammalian cells can be gap repaired by their co-transformation into yeast cells with an appropriate vector, the methods described in this manuscript should provide some of the necessary tools to isolate and characterize palindromic junctions from mammalian cells. JF - Nucleic acids research AU - Rattray, Alison J AD - GRCBL/NCI-FCRDC, PO Box B/ Building 539 Room 151, Frederick, MD 21702, USA. rattray@ncifcrf.gov Y1 - 2004/11/08/ PY - 2004 DA - 2004 Nov 08 SP - 1 VL - 32 IS - 19 KW - SAE2 protein, S cerevisiae KW - 0 KW - Saccharomyces cerevisiae Proteins KW - Sulfites KW - DNA KW - 9007-49-2 KW - Endonucleases KW - EC 3.1.- KW - sodium bisulfite KW - TZX5469Z6I KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Polymerase Chain Reaction KW - Base Sequence KW - Sequence Alignment KW - Sulfites -- chemistry KW - Saccharomyces cerevisiae Proteins -- genetics KW - Molecular Sequence Data KW - Plasmids -- chemistry KW - Sequence Analysis, DNA -- methods KW - DNA -- chemistry KW - Cloning, Molecular -- methods KW - Repetitive Sequences, Nucleic Acid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67063285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+method+for+cloning+and+sequencing+long+palindromic+DNA+junctions.&rft.au=Rattray%2C+Alison+J&rft.aulast=Rattray&rft.aufirst=Alison&rft.date=2004-11-08&rft.volume=32&rft.issue=19&rft.spage=e155&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 - 2004-11-19 N1 - Date created - 2004-11-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genetics. 1989 May;122(1):19-27 [2659436] Gene. 1987;57(2-3):267-72 [3319781] Ann N Y Acad Sci. 1999 May 18;870:45-57 [10415472] Yeast. 1993 Apr;9(4):351-61 [8511965] Mol Cell Biol. 1993 Sep;13(9):5315-22 [8395002] Nucleic Acids Res. 1994 Aug 11;22(15):2990-7 [8065911] Bioessays. 1994 Dec;16(12):893-900 [7840768] Mol Cell Biol. 1995 Oct;15(10):5607-17 [7565712] Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11274-8 [7479978] EMBO J. 1996 Mar 1;15(5):1163-71 [8605887] Genetics. 1997 Jul;146(3):781-95 [9215887] Genetics. 1997 Jul;146(3):797-816 [9215888] Genetics. 1997 Jul;146(3):835-47 [9215890] Mol Cell Biol. 1997 Sep;17(9):5559-70 [9271431] Genetics. 1998 Apr;148(4):1507-24 [9560370] Mol Cell. 1998 Jun;1(7):969-79 [9651580] Mol Gen Genet. 1998 Oct;259(6):639-44 [9819057] Mol Cell Biol. 1999 Jan;19(1):556-66 [9858579] Trends Biochem Sci. 2002 Aug;27(8):410-8 [12151226] BMC Genomics. 2003 Apr 29;4(1):16 [12720573] Genetics. 2003 Aug;164(4):1279-89 [12930739] Mol Cell Biol. 2000 May;20(10):3449-58 [10779335] EMBO J. 2000 Jul 17;19(14):3822-30 [10899135] Am J Hum Genet. 2001 Jan;68(1):1-13 [11095996] Genetics. 2001 May;158(1):109-22 [11333222] Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8326-33 [11459971] J Biol Chem. 2001 Sep 21;276(38):35458-64 [11454871] Cell. 2002 Jan 25;108(2):183-93 [11832209] Mol Cell. 2002 Apr;9(4):835-46 [11983174] Nat Rev Mol Cell Biol. 2002 May;3(5):317-27 [11988766] Genetics. 2002 May;161(1):461-8 [12019258] Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8772-7 [12060719] Methods. 2002 Jun;27(2):101-7 [12095266] Anal Biochem. 2002 Aug 1;307(1):13-7 [12137773] Mol Cell Biol. 2003 Dec;23(23):8740-50 [14612414] Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):204-9 [14673087] J Bacteriol. 1983 Jan;153(1):163-8 [6336730] Cell. 1986 May 9;45(3):425-30 [2870814] Proc Natl Acad Sci U S A. 1986 Jul;83(14):5194-8 [2425363] EMBO J. 1987 Aug;6(8):2401-8 [3665882] Nucleic Acids Res. 1990 May 25;18(10):2887-90 [2161516] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - QT interval increased after single dose of lofexidine. AN - 67046514; 15528619 JF - BMJ (Clinical research ed.) AU - Schmittner, John AU - Schroeder, Jennifer R AU - Epstein, David H AU - Preston, Kenzie L AD - National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. jschmitt@intra.nida.nih.gov Y1 - 2004/11/06/ PY - 2004 DA - 2004 Nov 06 SP - 1075 VL - 329 IS - 7474 KW - Narcotic Antagonists KW - 0 KW - Clonidine KW - MN3L5RMN02 KW - Methadone KW - UC6VBE7V1Z KW - lofexidine KW - UI82K0T627 KW - Abridged Index Medicus KW - Index Medicus KW - Methadone -- therapeutic use KW - Humans KW - Adult KW - Female KW - Long QT Syndrome -- chemically induced KW - Narcotic Antagonists -- therapeutic use KW - Narcotic Antagonists -- adverse effects KW - Clonidine -- analogs & derivatives KW - Clonidine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67046514?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BMJ+%28Clinical+research+ed.%29&rft.atitle=QT+interval+increased+after+single+dose+of+lofexidine.&rft.au=Schmittner%2C+John%3BSchroeder%2C+Jennifer+R%3BEpstein%2C+David+H%3BPreston%2C+Kenzie+L&rft.aulast=Schmittner&rft.aufirst=John&rft.date=2004-11-06&rft.volume=329&rft.issue=7474&rft.spage=1075&rft.isbn=&rft.btitle=&rft.title=BMJ+%28Clinical+research+ed.%29&rft.issn=1756-1833&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-24 N1 - Date created - 2004-11-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Prog Cardiovasc Dis. 2001 Mar-Apr;43(5 Suppl 1):1-45 [11269621] Arzneimittelforschung. 1982;32(8a):955-62 [6890369] Clin Pharmacol Ther. 1981 Dec;30(6):752-07 [7030578] N Engl J Med. 2004 Mar 4;350(10):1013-22 [14999113] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TIMP-1 stimulates proliferation of human aortic smooth muscle cells and Ras effector pathways. AN - 66936075; 15465038 AB - Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a multifunctional protein, which is found in most tissues and body fluids. Here, we demonstrated that recombinant TIMP-1 but not the synthetic matrix metalloproteinase inhibitor, GM6001, stimulated proliferation of human aortic smooth muscle cells (AoSMC) in a dose-dependent manner. The mitogenic effect was associated with activation of Ras, increased phosphorylation of ERK, and stimulation of cyclin D1 expression. The phosphatidylinositol 3-kinase (PI3K) signaling pathway was also involved since the PI3K inhibitor, LY294002, abolished the TIMP-1-mediated growth stimulation. These data suggest that TIMP-1 activates Ras, which then turns on the ERK and PI3K signaling pathways to promote cell cycle progression of the AoSMC. JF - Biochemical and biophysical research communications AU - Akahane, Takemi AU - Akahane, Manabu AU - Shah, Amy AU - Thorgeirsson, Unnur P AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. akahane@m5.kcn.ne.jp Y1 - 2004/11/05/ PY - 2004 DA - 2004 Nov 05 SP - 440 EP - 445 VL - 324 IS - 1 SN - 0006-291X, 0006-291X KW - Chromones KW - 0 KW - Dipeptides KW - Morpholines KW - N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide KW - Protease Inhibitors KW - Recombinant Proteins KW - Tissue Inhibitor of Metalloproteinase-1 KW - Cyclin D1 KW - 136601-57-5 KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Extracellular Signal-Regulated MAP Kinases KW - EC 2.7.11.24 KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Protease Inhibitors -- pharmacology KW - Animals KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Enzyme Activation KW - Humans KW - Morpholines -- pharmacology KW - Extracellular Signal-Regulated MAP Kinases -- metabolism KW - Cyclin D1 -- metabolism KW - Chromones -- pharmacology KW - Recombinant Proteins -- metabolism KW - Aorta -- anatomy & histology KW - Cell Line KW - Dipeptides -- pharmacology KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Myocytes, Smooth Muscle -- drug effects KW - Cell Proliferation -- drug effects KW - Tissue Inhibitor of Metalloproteinase-1 -- physiology KW - Myocytes, Smooth Muscle -- cytology KW - Tissue Inhibitor of Metalloproteinase-1 -- pharmacology KW - Myocytes, Smooth Muscle -- physiology KW - ras Proteins -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66936075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=TIMP-1+stimulates+proliferation+of+human+aortic+smooth+muscle+cells+and+Ras+effector+pathways.&rft.au=Akahane%2C+Takemi%3BAkahane%2C+Manabu%3BShah%2C+Amy%3BThorgeirsson%2C+Unnur+P&rft.aulast=Akahane&rft.aufirst=Takemi&rft.date=2004-11-05&rft.volume=324&rft.issue=1&rft.spage=440&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 - 2004-12-28 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression, purification, and biochemical characterization of the antiinflammatory tristetraprolin: a zinc-dependent mRNA binding protein affected by posttranslational modifications. AN - 67004324; 15504035 AB - Tristetraprolin (TTP) is a hyperphosphorylated protein that destabilizes mRNA by binding to an AU-rich element (ARE). Mice deficient in TTP develop a severe inflammatory syndrome. The biochemical properties of TTP have not been adequately characterized, due to the difficulties in protein purification and lack of a high-titer antiserum. Full-length human TTP was expressed in human HEK293 cells and purified to at least 70% homogeneity. The purified protein was free of endogenous ARE binding activity, and was used for investigating its size, zinc dependency, and binding kinetics for tumor necrosis factor alpha mRNA ARE. A high-titer rabbit antiserum was raised against the MBP-hTTP fusion protein expressed in Escherichia coli. Cellular localization studies of the transfected cells indicated that approximately 80% of the expressed TTP was in the cytosol, with 20% in the nuclei. TTP from both locations bound to the ARE and formed similar complexes. The purified TTP was shown to be intact by N-terminal His-tag purification, C-terminal peptide sequencing, and mass spectrometry analysis. Results from size exclusion chromatography are consistent with the predominant form of active TTP being a tetramer. TTP's ARE binding activity was increased by 10 microM Zn(2+). The half-maximal binding of TTP from HEK293 cells was approximately 30 nM in assays containing 10 nM ARE. This value was about twice that of TTP from E. coli. TTP from HEK293 cells was highly phosphorylated, and its electrophoretic mobility was increased by alkaline phosphatase treatment and somewhat by T271A mutation, but not by PNGase F or S186A mutation. The gel mobility of TTP from E. coli was decreased by in vitro phosphorylation with p42/ERK2 and p38 mitogen-activated protein kinases. These results suggest that TTP's zinc-dependent ARE binding affinity is reduced by half by posttranslational modifications, mainly by phosphorylation but not by glycosylation, in mammalian cells. The results support a model in which each subunit of the TTP tetramer binds to one of the five overlapping UUAUUUAUU sequences of the ARE, resulting in a stable TTP-ARE complex. JF - Biochemistry AU - Cao, Heping AD - Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. cao2@niehs.nih.gov Y1 - 2004/11/02/ PY - 2004 DA - 2004 Nov 02 SP - 13724 EP - 13738 VL - 43 IS - 43 SN - 0006-2960, 0006-2960 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Immediate-Early Proteins KW - Immune Sera KW - Inflammation Mediators KW - Maltose-Binding Proteins KW - RNA, Messenger KW - RNA-Binding Proteins KW - Recombinant Fusion Proteins KW - Tristetraprolin KW - ZFP36 protein, human KW - Zfp36 protein, mouse KW - Sodium Dodecyl Sulfate KW - 368GB5141J KW - Edetic Acid KW - 9G34HU7RV0 KW - Index Medicus KW - Animals KW - Recombinant Fusion Proteins -- biosynthesis KW - Carrier Proteins -- chemistry KW - Carrier Proteins -- immunology KW - Humans KW - Carrier Proteins -- genetics KW - Molecular Weight KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Recombinant Fusion Proteins -- genetics KW - Edetic Acid -- chemistry KW - Immune Sera -- chemistry KW - Immune Sera -- biosynthesis KW - Recombinant Fusion Proteins -- immunology KW - Sodium Dodecyl Sulfate -- chemistry KW - Mice KW - Plasmids KW - Carrier Proteins -- biosynthesis KW - Regulatory Sequences, Nucleic Acid KW - Transfection KW - Kinetics KW - Protein Binding -- genetics KW - Cell Line KW - Inflammation Mediators -- isolation & purification KW - RNA-Binding Proteins -- metabolism KW - RNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- chemistry KW - Immediate-Early Proteins -- metabolism KW - DNA-Binding Proteins -- genetics KW - Inflammation Mediators -- immunology KW - Immediate-Early Proteins -- chemistry KW - RNA-Binding Proteins -- chemistry KW - RNA-Binding Proteins -- isolation & purification KW - Immediate-Early Proteins -- isolation & purification KW - Inflammation Mediators -- metabolism KW - Immediate-Early Proteins -- genetics KW - RNA, Messenger -- metabolism KW - Protein Processing, Post-Translational -- genetics KW - Zinc Fingers -- genetics KW - DNA-Binding Proteins -- isolation & purification KW - Inflammation Mediators -- chemistry KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67004324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Expression%2C+purification%2C+and+biochemical+characterization+of+the+antiinflammatory+tristetraprolin%3A+a+zinc-dependent+mRNA+binding+protein+affected+by+posttranslational+modifications.&rft.au=Cao%2C+Heping&rft.aulast=Cao&rft.aufirst=Heping&rft.date=2004-11-02&rft.volume=43&rft.issue=43&rft.spage=13724&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-30 N1 - Date created - 2004-10-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Methods Enzymol. 1990;182:50-68 [2314256] Nucleic Acids Res. 1985 Jun 25;13(12):4417-29 [2989794] J Biol Chem. 1990 Nov 5;265(31):19185-91 [1699942] J Biol Chem. 1995 Jun 2;270(22):13341-7 [7768935] J Biol Chem. 1995 Oct 20;270(42):25266-72 [7559666] J Biol Chem. 1996 May 24;271(21):12179-84 [8647811] Immunity. 1996 May;4(5):445-54 [8630730] Anal Chem. 1996 Mar 1;68(5):850-8 [8779443] Mol Endocrinol. 1996 Feb;10(2):140-6 [8825554] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13754-9 [8943007] Science. 1997 Sep 5;277(5331):1453-62 [9278503] Science. 1998 Aug 14;281(5379):1001-5 [9703499] Plant Physiol. 1999 May;120(1):205-16 [10318698] Mol Cell Biol. 1999 Jun;19(6):4311-23 [10330172] Methods Mol Biol. 1999;118:115-28 [10549519] Arch Biochem Biophys. 2000 Jan 1;373(1):135-46 [10620332] J Biol Chem. 2000 Feb 11;275(6):4290-7 [10660597] Blood. 2000 Mar 15;95(6):1891-9 [10706852] J Biol Chem. 2000 Apr 7;275(14):10463-71 [10744736] Oncogene. 2000 Mar 23;19(13):1657-64 [10763822] J Biol Chem. 2000 Sep 1;275(35):27414-20 [10851244] Biochemistry. 2000 Oct 10;39(40):12303-11 [11015209] Nucleic Acids Res. 2001 Jan 1;29(1):246-54 [11125104] J Biol Chem. 2001 Apr 27;276(17):13530-40 [11152464] J Biol Chem. 2001 Jun 22;276(25):23144-54 [11279239] Am J Physiol Lung Cell Mol Physiol. 2001 Aug;281(2):L499-508 [11435226] Nucleic Acids Res. 2001 Jul 15;29(14):3020-9 [11452027] Mol Cell Biol. 2001 Oct;21(19):6461-9 [11533235] J Biol Chem. 2001 Nov 9;276(45):42580-7 [11546803] Cell. 2001 Nov 16;107(4):451-64 [11719186] J Biol Chem. 2002 Mar 29;277(13):11606-13 [11796723] J Biol Chem. 2002 May 17;277(20):18029-36 [11886850] Biochem Biophys Res Commun. 2002 May 17;293(4):1242-7 [12054509] Arthritis Rheum. 2002 May;46(5):1362-70 [12115244] Biochem Soc Trans. 2002 Nov;30(Pt 6):945-52 [12440952] J Biol Chem. 2002 Dec 13;277(50):48558-64 [12324455] Biochemistry. 2003 Jan 14;42(1):217-21 [12515557] Arch Biochem Biophys. 2003 Apr 1;412(1):106-20 [12646273] J Biol Chem. 2003 Apr 18;278(16):13912-8 [12578825] J Biol Chem. 2003 Apr 18;278(16):13928-35 [12578839] Biochemistry. 2003 Apr 29;42(16):4626-30 [12705825] Mol Cell Biol. 2003 Jun;23(11):3798-812 [12748283] J Biol Chem. 2003 May 30;278(22):19947-55 [12639954] J Natl Cancer Inst. 2003 Dec 17;95(24):1846-59 [14679154] Biochem Biophys Res Commun. 2004 Mar 5;315(2):445-9 [14766228] Curr Pharm Des. 2004;10(6):635-46 [14965326] Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2011-6 [14769925] Nat Struct Mol Biol. 2004 Mar;11(3):257-64 [14981510] J Biol Chem. 2004 Mar 12;279(11):10176-84 [14688255] EMBO J. 2004 Mar 24;23(6):1313-24 [15014438] J Biol Chem. 2004 May 14;279(20):21489-99 [15010466] J Immunol. 2004 Jun 15;172(12):7263-71 [15187101] J Biol Chem. 2004 Jul 2;279(27):27870-7 [15117938] J Biol Chem. 2004 Jul 30;279(31):32393-400 [15187092] J Virol. 2004 Aug;78(16):8582-92 [15280467] J Biol Chem. 1990 Sep 25;265(27):16556-63 [2204625] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of moderate alcohol consumption on folate and vitamin B sub(12) status in postmenopausal women AN - 954598944; 14031626 AB - BACKGROUND:: Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, a causal relationship has not been established, and the mechanisms mediating this association are speculative. Alcohol may act through altered status of folate and vitamin B sub(12), two vitamins required for DNA methylation and nucleotide synthesis, and thus cell integrity. Although the effects of heavy alcohol intake on folate and vitamin B sub(12) status have been well-documented, few studies have addressed the effects of moderate alcohol intake in a controlled setting. OBJECTIVE:: The objective of this study was to determine the effects of moderate alcohol intake on folate and vitamin B sub(12) status in healthy, well-nourished, postmenopausal women. DESIGN:: The study design was a randomized, diet-controlled crossover intervention. Postmenopausal women (n=53) received three 8-week alcohol treatments in random order: 0, 15, and 30g/day. Treatment periods were preceded by 2-5-week washout periods. Blood collected at baseline and week 8 of each treatment period was analyzed for serum folate, vitamin B sub(12), homocysteine (HCY), and methylmalonic acid (MMA) concentrations. RESULTS:: After adjusting for body mass index (BMI), a significant 5% decrease was observed in mean serum vitamin B sub(12) concentrations from 0 to 30g of alcohol/day (461.45 plus or minus 30.26 vs 440.25 plus or minus 30.24pg/ml; P=0.03). Mean serum HCY concentrations tended to increase by 3% from 0 to 30g of alcohol/day (9.44 plus or minus 0.37 vs 9.73 plus or minus 0.37 mu mol/l; P=0.05). Alcohol intake had no significant effects on serum folate or MMA concentrations. CONCLUSIONS:: Among healthy, well-nourished, postmenopausal women, moderate alcohol intake may diminish vitamin B sub(12) status. SPONSORSHIP:: NCI, NIH and ARS, USDA.European Journal of Clinical Nutrition (2004) 58, 1518-1524. doi:10.1038/sj.ejcn.1602002 Published online 12 May 2004 JF - European Journal of Clinical Nutrition AU - Laufer, E M AU - Hartman, T J AU - Baer, D J AU - Gunter, E W AU - Dorgan, J F AU - Campbell, W S AU - Clevidence, B A AU - Brown, E D AU - Albanes, D AU - Judd, J T AU - Taylor, P R AD - 5 The National Cancer Institute, Bethesda, MD, USA Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 1518 EP - 1524 PB - Nature Publishing Group VL - 58 IS - 11 SN - 0954-3007, 0954-3007 KW - Risk Abstracts KW - Alcohol KW - post-menopause KW - Nutrition KW - Cancer KW - vitamins KW - body mass KW - intervention KW - Breast cancer KW - Females KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954598944?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Clinical+Nutrition&rft.atitle=Effects+of+moderate+alcohol+consumption+on+folate+and+vitamin+B+sub%2812%29+status+in+postmenopausal+women&rft.au=Laufer%2C+E+M%3BHartman%2C+T+J%3BBaer%2C+D+J%3BGunter%2C+E+W%3BDorgan%2C+J+F%3BCampbell%2C+W+S%3BClevidence%2C+B+A%3BBrown%2C+E+D%3BAlbanes%2C+D%3BJudd%2C+J+T%3BTaylor%2C+P+R&rft.aulast=Laufer&rft.aufirst=E&rft.date=2004-11-01&rft.volume=58&rft.issue=11&rft.spage=1518&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Clinical+Nutrition&rft.issn=09543007&rft_id=info:doi/10.1038%2Fsj.ejcn.1602002 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2012-03-30 N1 - SubjectsTermNotLitGenreText - Alcohol; vitamins; post-menopause; body mass; intervention; Breast cancer; Females; Nutrition; Cancer DO - http://dx.doi.org/10.1038/sj.ejcn.1602002 ER - TY - JOUR T1 - Vocabulary Competence in First- and Secondborn Siblings of the Same Chronological Age AN - 85614011; 200504883 AB - We explored vocabulary competence in 55 firstborn & secondborn sibling pairs when each child reached 1;8 using multiple measures of maternal report, child speech, & experimenter assessment. Measures from each of the three sources were interrelated. Firstborns' vocabulary competence exceeded secondborns' only in maternal reports, not in child speech or in experimenter assessments. Firstborn girls outperformed boys on all vocabulary competence measures, & secondborn girls outperformed boys on most measures. Vocabulary competence was independent of the gender composition &, generally, of the age difference in sibling pairs. Vocabulary competence in firstborns & secondborns was only weakly related. 2 Tables, 41 References. Adapted from the source document JF - Journal of Child Language AU - Bornstein, Marc H AU - Leach, Diane B AU - Haynes, O Maurice AD - National Instit Health, Bethesda, MD Marc_H_Bornstein@nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 855 EP - 873 VL - 31 IS - 4 SN - 0305-0009, 0305-0009 KW - birth order KW - Siblings (78220) KW - Infants (35660) KW - Speech Perception (82700) KW - Linguistic Competence (47400) KW - Language Acquisition (41600) KW - Parents (62770) KW - Lexicon (47150) KW - Sex Differences (77850) KW - article KW - 4015: psycholinguistics; child language acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85614011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Child+Language&rft.atitle=Vocabulary+Competence+in+First-+and+Secondborn+Siblings+of+the+Same+Chronological+Age&rft.au=Bornstein%2C+Marc+H%3BLeach%2C+Diane+B%3BHaynes%2C+O+Maurice&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=2004-11-01&rft.volume=31&rft.issue=4&rft.spage=855&rft.isbn=&rft.btitle=&rft.title=Journal+of+Child+Language&rft.issn=03050009&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2005-05-01 N1 - Last updated - 2016-09-27 N1 - CODEN - JCLGBJ N1 - SubjectsTermNotLitGenreText - Language Acquisition (41600); Siblings (78220); Infants (35660); Speech Perception (82700); Parents (62770); Sex Differences (77850); Lexicon (47150); Linguistic Competence (47400) ER - TY - JOUR T1 - Connectionist approaches to understanding aphasic perseveration. AN - 85411807; pmid-15599822 AB - Aphasic patients make a variety of speech errors, including perseverations, in tasks that involve a linguistic component. What do perseverative and other errors imply about the nature of the neurologically damaged and intact language systems? Here we discuss the insights into the mechanisms of aphasic perseveration afforded by connectionist models. As a base for discussion, we review the Plaut and Shallice model of optic aphasic errors in object naming, which relies primarily on short-term learning mechanisms to produce perseverations. We then point out limitations of the model in addressing more recent data collected on aphasic perseveration and explain how incorporating information about the interaction of neuromodulatory systems and learning in the brain may help to overcome these limitations. JF - Seminars in speech and language AU - Gotts, Stephen J AU - Plaut, David C AD - Department of Psychology, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA. gotts@nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 323 EP - 334 VL - 25 IS - 4 SN - 0734-0478, 0734-0478 KW - Index Medicus KW - National Library of Medicine KW - Aphasia: complications KW - *Aphasia: physiopathology KW - Brain Damage, Chronic: complications KW - Brain Damage, Chronic: physiopathology KW - Computer Simulation KW - Humans KW - Language Disorders: etiology KW - Language Disorders: physiopathology KW - Learning: physiology KW - *Models, Neurological KW - Neurotransmitter Agents: physiology KW - Recurrence KW - Speech Disorders: etiology KW - Speech Disorders: physiopathology KW - Verbal Behavior: physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85411807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+speech+and+language&rft.atitle=Connectionist+approaches+to+understanding+aphasic+perseveration.&rft.au=Gotts%2C+Stephen+J%3BPlaut%2C+David+C&rft.aulast=Gotts&rft.aufirst=Stephen&rft.date=2004-11-01&rft.volume=25&rft.issue=4&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=Seminars+in+speech+and+language&rft.issn=07340478&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Clinical features of adult GM1 gangliosidosis: report of three Indian patients and review of 40 cases. AN - 85372330; pmid-15389993 AB - Deficiency of enzyme acid beta-galactosidase causes GM1 gangliosidosis. Patients with adult GM1 gangliosidosis typically present with generalized dystonia. We describe clinical, bone marrow, and radiological features of adult GM1 gangliosidosis to help improve its recognition. We report 3 Indian patients and review of reports between 1981 and October 2002. The disease frequently is reported in the Japanese literature (75%). Patients are normal at birth and have normal early motor and mental development. Onset is within the first decade with abnormal gait, or worsening of speech is an initial symptom. Dystonia occurs in 97% of patients. Facial dystonia described as "facial grimacing" observed in approximately 90% could be an important clinical clue. Dysarthria/anarthria (97%) is frequent, and eye movements are normal. Bone marrow examination may show Gaucher-like foam cells (39%). Magnetic resonance imaging (MRI) frequently (90.9%) shows bilateral symmetrical putamenal hyperintensities on T2-weighted and proton density images. Diagnosis is confirmed by demonstrating deficiency of beta-galactosidase. Adult (Type 3) GM1 Gangliosidosis commonly presents with generalized dystonia with prominent facial dystonia, severe speech disturbances, and normal eye movements. Bone marrow frequently shows Gaucher-like foam cells. MRI shows typical lesions in the putamen. Deficiency of beta-galactosidase in fibroblasts confirms the diagnosis. JF - Movement disorders : official journal of the Movement Disorder Society AU - Muthane, Uday AU - Chickabasaviah, Yasha AU - Kaneski, Chris AU - Shankar, Susurla K AU - Narayanappa, Gayathri AU - Christopher, Rita AU - Govindappa, Srikanth Subbamma AD - Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. umuthane@usa.net Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 1334 EP - 1341 VL - 19 IS - 11 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Adolescent KW - Adult KW - Bone Marrow: pathology KW - Consanguinity KW - Diagnosis, Differential KW - Dominance, Cerebral: physiology KW - *Dystonia: diagnosis KW - Dystonia: genetics KW - Dystonia: therapy KW - Female KW - *Gangliosidosis, GM1: diagnosis KW - Gangliosidosis, GM1: genetics KW - Gangliosidosis, GM1: therapy KW - Humans KW - India KW - Intellectual Disability: diagnosis KW - Intellectual Disability: genetics KW - Intellectual Disability: therapy KW - Magnetic Resonance Imaging KW - Male KW - Neurologic Examination KW - Neuropsychological Tests KW - Parkinsonian Disorders: diagnosis KW - Parkinsonian Disorders: genetics KW - Parkinsonian Disorders: therapy KW - Putamen: pathology KW - Speech Disorders: diagnosis KW - Speech Disorders: genetics KW - Speech Disorders: therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85372330?accountid=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=Clinical+features+of+adult+GM1+gangliosidosis%3A+report+of+three+Indian+patients+and+review+of+40+cases.&rft.au=Muthane%2C+Uday%3BChickabasaviah%2C+Yasha%3BKaneski%2C+Chris%3BShankar%2C+Susurla+K%3BNarayanappa%2C+Gayathri%3BChristopher%2C+Rita%3BGovindappa%2C+Srikanth+Subbamma&rft.aulast=Muthane&rft.aufirst=Uday&rft.date=2004-11-01&rft.volume=19&rft.issue=11&rft.spage=1334&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 - Processing of Complex Sentences in a Case of Aphasia in Indonesian: Thematic vs. Linear Strategies AN - 85332679; llba-200501737 AB - The comprehension of HS, an Indonesian-speaking man with non-fluent aphasia, was investigated using an act-out task. HS was tested on VP-conjoined & center-embedded constructions in Indonesian that contained either two active verbs or two passive verbs, an active verb in the first clause & a passive verb in the second clause, or vice versa. Another type of center-embedded construction contained an object-preposed verb in the embedded clause & either an active or passive verb in the matrix clause. HS enacted the first clause accurately on all sentence types, yet he consistently predicated the second verb of the NP with the role of agent in the first clause. This strategy resulted in appropriate enactments of sentences with an active verb in the first clause, but it led to ungrammatical interpretations of sentences whose first clause contained a passive or object-preposed verb, since in these constructions the subject of the second verb is the NP with the role of theme in the first clause. HS's response pattern supports a new computational model, the Thematic Prominence Model, which posits that in thematically oriented, free word order languages like Indonesian, the thematic prominence of arguments is more important for predication than their linear positions. 4 Figures, 1 Appendix, 41 References. [Copyright 2004 Elsevier Ltd.] JF - Journal of Neurolinguistics AU - Postman, Whitney Anne AD - National Instit Deafness & Communication Disorders, National Instit Health, Bethesda, MD postmanw@nidcd.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 455 EP - 489 VL - 17 IS - 6 SN - 0911-6044, 0911-6044 KW - *Voice (Grammatical) (94950) KW - *Brocas Aphasia (09750) KW - *Comprehension (13950) KW - *Word Order (97800) KW - *Argument Structure (03970) KW - *Thematic Roles (89300) KW - *Malay (50740) KW - *Embedded Construction (21550) KW - *Verbs (93900) KW - article KW - 6414: language-pathological and normal; aphasia UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85332679?accountid=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+Neurolinguistics&rft.atitle=Processing+of+Complex+Sentences+in+a+Case+of+Aphasia+in+Indonesian%3A+Thematic+vs.+Linear+Strategies&rft.au=Postman%2C+Whitney+Anne&rft.aulast=Postman&rft.aufirst=Whitney&rft.date=2004-11-01&rft.volume=17&rft.issue=6&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurolinguistics&rft.issn=09116044&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2005-02-01 N1 - Last updated - 2014-06-17 N1 - CODEN - JONEE8 N1 - SubjectsTermNotLitGenreText - *Comprehension (13950); *Brocas Aphasia (09750); *Malay (50740); *Verbs (93900); *Voice (Grammatical) (94950); *Embedded Construction (21550); *Thematic Roles (89300); *Argument Structure (03970); *Word Order (97800) ER - TY - JOUR T1 - Oral administration of an AT1 receptor antagonist prevents the central effects of angiotensin II in spontaneously hypertensive rats. AN - 85300267; pmid-15518636 AB - Peripheral and brain angiotensin II AT(1) receptor blockade decreases high blood pressure, stress, and neuronal injury. To clarify the effects of long-term brain Ang II receptor blockade, the AT(1) blocker, candesartan, was orally administered to spontaneously hypertensive rats (SHRs) for 40 days, followed by intraventricular injection of 25 ng of Ang II. Before Ang II injection, AT(1) receptor blockade normalized blood pressure and decreased plasma adrenocorticotropic hormone (ACTH) and corticosterone. After central administration of excess Ang II, the reduction of ACTH and corticosterone release induced by AT(1) receptor blockade no longer occurred. Central Ang II administration to vehicle-treated SHRs further increased blood pressure, provoked drinking, increased tyrosine hydroxylase (TH) mRNA expression in the locus coeruleus, and stimulated sympathoadrenal catecholamine release. Pretreatment with the AT(1) receptor antagonist eliminated Ang II-induced increases in blood pressure, water intake, and sympathoadrenal catecholamine release; inhibited peripheral and brain AT(1) receptors; increased AT(2) receptor binding in the locus coeruleus, inferior olive, and adrenal cortex; and decreased AT(2) receptor binding in the adrenal medulla. Inhibition of brain AT(1) receptors correlated with decreased TH transcription in the locus coeruleus, indicating a decreased central sympathetic drive. This, and the diminished adrenomedullary AT(1) and AT(2) receptor stimulation, result in decreased sympathoadrenomedullary stimulation. Oral administration of AT(1) antagonists can effectively block central actions of Ang II, regulating blood pressure and reaction to stress, and selectively and differentially modulating sympathoadrenal response and the hypothalamic-pituitary-adrenal stimulation produced by brain Ang II--effects of potential therapeutic importance. JF - Brain Research AU - Seltzer, Alicia AU - Bregonzio Claudia AU - Armando Inés AU - Baiardi Gustavo AU - Saavedra, Juan M AD - Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bldg 10, Rm 2D57, 10 Center Dr, MSC-1514, Bethesda, MD 20892, USA. PY - 2004 SP - 9 EP - 18 VL - 1028 IS - 1 SN - 0006-8993, 0006-8993 KW - Administration, Oral KW - Animals KW - Catechols KW - Drug Interactions KW - Analysis of Variance KW - Drug Administration Schedule KW - Rats, Inbred SHR KW - Blood Pressure KW - Receptor, Angiotensin, Type 1 KW - Locus Coeruleus KW - Tyrosine 3-Monooxygenase KW - Angiotensin II KW - Corticotropin KW - Injections, Intraventricular KW - Benzimidazoles KW - Angiotensin II Type 1 Receptor Blockers KW - RNA, Messenger KW - Rats KW - Research Support, Non-U.S. Gov't KW - Corticosterone KW - Comparative Study KW - Adrenal Glands KW - Tetrazoles KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85300267?accountid=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=Oral+administration+of+an+AT1+receptor+antagonist+prevents+the+central+effects+of+angiotensin+II+in+spontaneously+hypertensive+rats.&rft.au=Seltzer%2C+Alicia%3BBregonzio+Claudia%3BArmando+In%C3%A9s%3BBaiardi+Gustavo%3BSaavedra%2C+Juan+M&rft.aulast=Seltzer&rft.aufirst=Alicia&rft.date=2004-11-01&rft.volume=1028&rft.issue=1&rft.spage=9&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 - Bipolar depression: the role of atypical antipsychotics. AN - 67314267; 16279863 AB - Acute manic episodes in bipolar disorder require rapid and effective relief. Bipolar depression is a major component of the bipolar disorder spectrum. Existing treatment options for bipolar depression include lithium, lamotrigine and conventional antidepressants. However, lithium is more effective in treating mania or hypomania than depression, both acutely and prophylactically, lamotrigine has only been demonstrated to be effective in one adequately powered study in acute bipolar I depression, and conventional antidepressants have been associated with emergent mania and cycle acceleration. Symptomatic outpatients can expect to spend, on average, 33% of their time in the depressive phase compared with 11% in the manic phase. Consequently, there is a need for additional agents to effectively treat bipolar depression. The atypical agents olanzapine, risperidone and quetiapine have demonstrated efficacy against the manic phase of bipolar disorder and appear also to have potential in the depressive phase. Olanzapine monotherapy significantly improved depressive symptoms compared with placebo in patients with bipolar disorder in an 8-week randomized, controlled clinical study, but the magnitude of the clinical effect was small. The observed improvement in depressive symptoms became moderately large when olanzapine was combined with the antidepressant fluoxetine. Quetiapine monotherapy also resulted in significant improvements compared with placebo in patients with either bipolar I or bipolar II disorder in another 8-week randomized, controlled clinical study, but the effect size was large. A 6-month open-label study of risperidone added to ongoing therapy demonstrated improvements in depressive symptoms in patients with bipolar and schizoaffective disorders experiencing a manic, hypomanic, mixed or depressive episode. The receptor-binding profile of these agents supports a role in the treatment of depressive symptoms and clinical data are beginning to emerge of their efficacy in both the acute and maintenance setting. JF - Expert review of neurotherapeutics AU - Post, Robert M AU - Calabrese, Joseph R AD - robert.post@nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - S27 EP - S33 VL - 4 IS - 6 Suppl 2 KW - Antipsychotic Agents KW - 0 KW - Benzodiazepines KW - 12794-10-4 KW - Risperidone KW - L6UH7ZF8HC KW - olanzapine KW - N7U69T4SZR KW - Index Medicus KW - Drug Tolerance KW - Benzodiazepines -- therapeutic use KW - Humans KW - Follow-Up Studies KW - Time Factors KW - Risperidone -- therapeutic use KW - Psychotic Disorders -- drug therapy KW - Antipsychotic Agents -- therapeutic use KW - Bipolar Disorder -- drug therapy KW - Antipsychotic Agents -- adverse effects KW - Antipsychotic Agents -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67314267?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+review+of+neurotherapeutics&rft.atitle=Bipolar+depression%3A+the+role+of+atypical+antipsychotics.&rft.au=Post%2C+Robert+M%3BCalabrese%2C+Joseph+R&rft.aulast=Post&rft.aufirst=Robert&rft.date=2004-11-01&rft.volume=4&rft.issue=6+Suppl+2&rft.spage=S27&rft.isbn=&rft.btitle=&rft.title=Expert+review+of+neurotherapeutics&rft.issn=1744-8360&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-04-14 N1 - Date created - 2005-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Building a collaborative research agenda: drug abuse and HIV/AIDS in the Caribbean 2002-2004. AN - 67269124; 15819335 JF - The West Indian medical journal AU - National Institute on Drug Abuse AU - Caribbean Epidemiology Centre AU - Pan American Health Organization AU - World Health Organization AD - National Institute on Drug Abuse ; Caribbean Epidemiology Centre ; Pan American Health Organization ; World Health Organization Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 1 EP - 78 VL - 53 Suppl 4 SN - 0043-3144, 0043-3144 KW - Crack Cocaine KW - 0 KW - Index Medicus KW - Caribbean Region -- epidemiology KW - Humans KW - Research KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - HIV Infections -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67269124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+West+Indian+medical+journal&rft.atitle=Building+a+collaborative+research+agenda%3A+drug+abuse+and+HIV%2FAIDS+in+the+Caribbean+2002-2004.&rft.au=National+Institute+on+Drug+Abuse%3BCaribbean+Epidemiology+Centre%3BPan+American+Health+Organization%3BWorld+Health+Organization&rft.aulast=National+Institute+on+Drug+Abuse&rft.aufirst=&rft.date=2004-11-01&rft.volume=53+Suppl+4&rft.issue=&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=The+West+Indian+medical+journal&rft.issn=00433144&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-27 N1 - Date created - 2005-04-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Survey on health status of workers exposed in the past to carcinogens in a glass factory in Leghorn, Italy]. TT - Indagine sullo stato di salute di ex-esposti ad agenti cancerogeni di una vetreria industriale. AN - 67267817; 15732256 AB - For a few years now in Italy there has been wide discussion on the advisability of developing health surveillance programmes for workers who were exposed to occupational carcinogens in the past (incompliance with Italian D.Lgs. 626/94, art. No. 69). The purpose of the present paper was to contribute to the discussion on operative guidelines for public or private Occupational Health Services intending to address this issue. A cross-sectional survey was undertaken on former workers of a glass factory located in Leghorn, Italy. Six hundred and seventy-seven workers discharged in the period 1/1/1942 - 30/6/1992, with at least 1 year of service, resident in the area of Leghorn, were identified from the personnel records of the company and invited to medical examination at the local public Occupational Health Service. A structured questionnaire was developed in order to standardize the collection of occupational and health histories. 370 subjects were examined and for each of them occupational and health histories were collected. Occupational exposure to carcinogens in the factory in the last decades was reconstructed using the workers' occupational histories and the available plant records: 3 periods with different production activities (1942/49, 1950/69, 1970/92), and 4 main carcinogens (asbestos, PAH, silica and glass fibres) were identified. Thirty cancers were recorded and 10 of these were occupationally related. The health survey allowed occupational exposures to carcinogens to be defined in a factory where historical environmental data were not available. It was also possible to assess individual past occupational risk and provide information to each former worker on his risk, on available preventive measures, and on possible diagnostic, therapeutic and insurance procedures available in relation to diseases related to the different hazards. Via this survey it was also possible to identify and notify the Italian Institute of Insurance against Occupational Diseases and Accidents of 6 cases of bladder cancer, i.e., cancers with long survival that would be impossible to identify via current health data bases. JF - La Medicina del lavoro AU - Rossi, Oriana AU - Turini, L AU - Chellini, Elisabetta AU - Buonocore, C AU - Loi, Anna Maria AD - UO Prevenzione Igiene e Salute nei Luoghi di Lavoro, Azienda USL 6 Livorno. o.rossi@usl6.toscana.it PY - 2004 SP - 465 EP - 474 VL - 95 IS - 6 SN - 0025-7818, 0025-7818 KW - Carcinogens KW - 0 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Humans KW - Aged KW - Male KW - Italy KW - Occupational Exposure KW - Health Surveys KW - Health Status KW - Asbestos -- adverse effects KW - Glass KW - Industry KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67267817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=%5BSurvey+on+health+status+of+workers+exposed+in+the+past+to+carcinogens+in+a+glass+factory+in+Leghorn%2C+Italy%5D.&rft.au=Rossi%2C+Oriana%3BTurini%2C+L%3BChellini%2C+Elisabetta%3BBuonocore%2C+C%3BLoi%2C+Anna+Maria&rft.aulast=Rossi&rft.aufirst=Oriana&rft.date=2004-11-01&rft.volume=95&rft.issue=6&rft.spage=465&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 - 2005-09-29 N1 - Date created - 2005-02-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Uridine diphosphoglucuronosyl transferase and methylenetetrahydrofolate reductase polymorphisms as genomic predictors of toxicity and response to irinotecan-, antifolate- and fluoropyrimidine-based chemotherapy. AN - 67243206; 15688606 AB - Pharmacogenetics could be a useful tool for performing tailored anticancer chemotherapy. Several polymorphisms potentially affecting enzymes responsible for metabolism, transport and mechanism of action of irinotecan, fluoropyrimidines and antifolate agents have been investigated and sometimes associated with toxicity and response. In particular, uridine diphosphoglucuronosyl transferase 1A1 (UGT1A1) enzyme is responsible for detoxification of irinotecan active metabolite, SN38. A polymorphic structure in the promoter region (UGT1A1*28) may affect irinotecan toxicity and SN38 plasma level. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate cycle, presenting two common polymorphisms (677C>T and 1298 A>C) which have impact on toxicity and efficacy of methotrexate and 5-fluorouracil. JF - Journal of chemotherapy (Florence, Italy) AU - Toffoli, G AU - Cecchin, E AD - Experimental and Clinical Pharmacology, CRO - National Cancer Institute, Via Pedemontana Occidentale 12, 33081 Aviano, Italy. gtoffoli@cro.it Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 31 EP - 35 VL - 16 Suppl 4 SN - 1120-009X, 1120-009X KW - irinotecan KW - 0H43101T0J KW - Methylenetetrahydrofolate Reductase (NADPH2) KW - EC 1.5.1.20 KW - UGT1A1 enzyme KW - EC 2.4.1.- KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Fluorouracil KW - U3P01618RT KW - Camptothecin KW - XT3Z54Z28A KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Sensitivity and Specificity KW - Fluorouracil -- therapeutic use KW - Fluorouracil -- adverse effects KW - Methotrexate -- adverse effects KW - Humans KW - Methotrexate -- therapeutic use KW - Toxicogenetics KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Glucuronosyltransferase -- genetics KW - Polymorphism, Genetic KW - Camptothecin -- analogs & derivatives KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Camptothecin -- therapeutic use KW - Camptothecin -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Pharmacogenetics KW - Neoplasms -- genetics KW - Methylenetetrahydrofolate Reductase (NADPH2) -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67243206?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chemotherapy+%28Florence%2C+Italy%29&rft.atitle=Uridine+diphosphoglucuronosyl+transferase+and+methylenetetrahydrofolate+reductase+polymorphisms+as+genomic+predictors+of+toxicity+and+response+to+irinotecan-%2C+antifolate-+and+fluoropyrimidine-based+chemotherapy.&rft.au=Toffoli%2C+G%3BCecchin%2C+E&rft.aulast=Toffoli&rft.aufirst=G&rft.date=2004-11-01&rft.volume=16+Suppl+4&rft.issue=&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Journal+of+chemotherapy+%28Florence%2C+Italy%29&rft.issn=1120009X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-01 N1 - Date created - 2005-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TNFa-based isolated hyperthermic limb perfusion (HILP) in the treatment of limb recurrent melanoma: update 16 years after its first clinical application. AN - 67225317; 15675482 AB - Hyperthermic Limb Perfusion (HILP) with Tumor Necrosis Factor alpha (TNFalpha) and interferon gamma (IFNgamma) was pioneered by Liénard and Lejeune in 1988. TNFalpha was empirically employed at a dosage of 3-4 mg that is ten times the systemic maximum tolerated dose (MTD). Sixteen years after its first clinical application more than 300 patients have been treated and some clarifications can be made regarding three major questions: the real role of IFNgamma, the TNFalpha dose and eligibility criteria for patient selection. A randomized phase II study has demonstrated that IFNgamma does not increase significantly the efficacy but does increase side-effects. Experimental and clinical results seem to indicate that patients with bulky melanoma disease can really benefit from TNFalpha HILP carried out with only 1 mg. JF - Journal of chemotherapy (Florence, Italy) AU - Di Filippo, F AU - Cavaliere, F AU - Garinei, R AU - Anzà, M AU - Di Angelo, P AU - Psaila, A AU - Piarulli, L AU - Callopoli, A AU - Bruno, P AU - Di Filippo, S AU - Priore, F AD - Regina Elena National Cancer Institute, Rome, Italy. difilippo@ifo.it Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 62 EP - 65 VL - 16 Suppl 5 SN - 1120-009X, 1120-009X KW - Tumor Necrosis Factor-alpha KW - 0 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Extremities KW - Animals KW - Humans KW - Interferon-gamma -- pharmacology KW - Maximum Tolerated Dose KW - Recurrence KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Melanoma -- drug therapy KW - Hyperthermia, Induced KW - Chemotherapy, Cancer, Regional Perfusion -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67225317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+chemotherapy+%28Florence%2C+Italy%29&rft.atitle=TNFa-based+isolated+hyperthermic+limb+perfusion+%28HILP%29+in+the+treatment+of+limb+recurrent+melanoma%3A+update+16+years+after+its+first+clinical+application.&rft.au=Di+Filippo%2C+F%3BCavaliere%2C+F%3BGarinei%2C+R%3BAnz%C3%A0%2C+M%3BDi+Angelo%2C+P%3BPsaila%2C+A%3BPiarulli%2C+L%3BCallopoli%2C+A%3BBruno%2C+P%3BDi+Filippo%2C+S%3BPriore%2C+F&rft.aulast=Di+Filippo&rft.aufirst=F&rft.date=2004-11-01&rft.volume=16+Suppl+5&rft.issue=&rft.spage=62&rft.isbn=&rft.btitle=&rft.title=Journal+of+chemotherapy+%28Florence%2C+Italy%29&rft.issn=1120009X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-10 N1 - Date created - 2005-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A review of the effect of an accommodation program to support nurses with functional limitations. AN - 67220657; 15651590 AB - The National Institutes of Health Clinical Center, Nursing and Patient Care Services, has developed a program to manage staff with functional restrictions using consistent processes and assignments that support the goals of the department while helping to contain costs. JF - Nursing economic$ AU - Koviack, Pamela AD - National Institutes of Health, Clinical Center, Nursing and Patient Care Services, NPCS Medical and Reasonable Accommodation Program, Bethesda, MD, USA. PY - 2004 SP - 291 EP - 4, 355, 291 VL - 22 IS - 6 SN - 0746-1739, 0746-1739 KW - Nursing KW - Workers' Compensation -- economics KW - United States KW - Attitude of Health Personnel KW - Humans KW - Job Description KW - Cost Savings KW - Eligibility Determination KW - Research Personnel -- supply & distribution KW - National Institutes of Health (U.S.) KW - Program Development KW - Program Evaluation KW - Social Support KW - Accidents, Occupational KW - Wounds and Injuries -- rehabilitation KW - Rehabilitation, Vocational -- methods KW - Occupational Health Services -- organization & administration KW - Nursing Staff -- supply & distribution KW - Activities of Daily Living KW - Occupational Diseases -- rehabilitation KW - Nursing Staff -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67220657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nursing+economic%24&rft.atitle=A+review+of+the+effect+of+an+accommodation+program+to+support+nurses+with+functional+limitations.&rft.au=Koviack%2C+Pamela&rft.aulast=Koviack&rft.aufirst=Pamela&rft.date=2004-11-01&rft.volume=22&rft.issue=6&rft.spage=291&rft.isbn=&rft.btitle=&rft.title=Nursing+economic%24&rft.issn=07461739&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-04 N1 - Date created - 2005-01-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nurs Econ. 2005 May-Jun;23(3):140 [16033146] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lung cancer in Mayak workers. AN - 67205702; 15624305 AB - The cohort of nuclear workers at the Mayak Production Association, located in the Russian Federation, is a unique resource for providing information on the health effects of exposure to plutonium as well as the effects of protracted external dose. Lung cancer mortality risks were evaluated in 21,790 Mayak workers, a much larger group than included in previous evaluations of lung cancer risks in this cohort. These analyses, which included 655 lung cancer deaths occurring in the period 1955-2000, were the first to evaluate both excess relative risk (ERR) and excess absolute risk (EAR) models and to give detailed attention to the modifying effects of gender, attained age and age at hire. Lung cancer risks were found to be significantly related to both internal dose to the lung from plutonium and external dose, and risks were described adequately by linear functions. For internal dose, the ERR per gray for females was about four times higher than that for males, whereas the EAR for females was less than half that for males; the ERR showed a strong decline with attained age, whereas the EAR increased with attained age until about age 65 and then decreased. Parallel analyses of lung cancer mortality risks in Mayak workers and Japanese A-bomb survivors were also conducted. Efforts currently under way to improve both internal and external dose estimates, and to develop data on smoking, should result in more accurate risk estimates in the future. JF - Radiation research AU - Gilbert, E S AU - Koshurnikova, N A AU - Sokolnikov, M E AU - Shilnikova, N S AU - Preston, D L AU - Ron, E AU - Okatenko, P V AU - Khokhryakov, V F AU - Vasilenko, E K AU - Miller, S AU - Eckerman, K AU - Romanov, S A AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20852, USA. gilberte@exchange.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 505 EP - 516 VL - 162 IS - 5 SN - 0033-7587, 0033-7587 KW - Plutonium KW - 53023GN24M KW - Index Medicus KW - Space life sciences KW - Occupational Exposure KW - Age Factors KW - Sex Factors KW - Humans KW - Models, Statistical KW - Nuclear Reactors KW - Risk KW - Nuclear Warfare KW - Plutonium -- adverse effects KW - Adult KW - Cohort Studies KW - Middle Aged KW - Russia KW - Adolescent KW - Time Factors KW - Female KW - Japan KW - Male KW - Lung -- radiation effects KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Neoplasms, Radiation-Induced -- mortality KW - Lung Neoplasms -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67205702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Lung+cancer+in+Mayak+workers.&rft.au=Gilbert%2C+E+S%3BKoshurnikova%2C+N+A%3BSokolnikov%2C+M+E%3BShilnikova%2C+N+S%3BPreston%2C+D+L%3BRon%2C+E%3BOkatenko%2C+P+V%3BKhokhryakov%2C+V+F%3BVasilenko%2C+E+K%3BMiller%2C+S%3BEckerman%2C+K%3BRomanov%2C+S+A&rft.aulast=Gilbert&rft.aufirst=E&rft.date=2004-11-01&rft.volume=162&rft.issue=5&rft.spage=505&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 - 2005-01-13 N1 - Date created - 2004-12-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phototoxicity in human lens epithelial cells promoted by St. John's Wort. AN - 67193931; 15623347 AB - St. John's Wort (SJW), an over-the-counter antidepressant, contains hypericin, which absorbs light in the UV and visible ranges and is phototoxic to skin. To determine if it also could be phototoxic to the eye, we exposed human lens epithelial cells to 0.1-10 microM hypericin and irradiated them with 4 J/cm2 UV-A or 0.9 J/cm2 visible light. Neither hypericin exposure alone nor light exposure alone reduced cell viability. In contrast, cells exposed to hypericin in combination with UV-A or visible light underwent necrosis and apoptosis. The ocular antioxidants lutein and N-acetyl cysteine did not prevent damage. Thus, ingested SJW is potentially phototoxic to the eye and could contribute to early cataractogenesis. Precautions should be taken to protect the eye from intense sunlight while taking SJW. JF - Photochemistry and photobiology AU - He, Yu-Ying AU - Chignell, Colin F AU - Miller, David S AU - Andley, Usha P AU - Roberts, Joan E AD - Laboratory of Chemistry and Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 10023, USA. PY - 2004 SP - 583 EP - 586 VL - 80 IS - 3 SN - 0031-8655, 0031-8655 KW - Photosensitizing Agents KW - 0 KW - Perylene KW - 5QD5427UN7 KW - hypericin KW - 7V2F1075HD KW - Index Medicus KW - Perylene -- pharmacology KW - Perylene -- analogs & derivatives KW - Humans KW - Cell Death -- radiation effects KW - Cell Death -- drug effects KW - Cell Line KW - Photosensitizing Agents -- toxicity KW - Epithelial Cells -- cytology KW - Epithelial Cells -- drug effects KW - Lens, Crystalline -- cytology KW - Lens, Crystalline -- drug effects KW - Hypericum -- toxicity KW - Lens, Crystalline -- radiation effects KW - Epithelial Cells -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67193931?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Phototoxicity+in+human+lens+epithelial+cells+promoted+by+St.+John%27s+Wort.&rft.au=He%2C+Yu-Ying%3BChignell%2C+Colin+F%3BMiller%2C+David+S%3BAndley%2C+Usha+P%3BRoberts%2C+Joan+E&rft.aulast=He&rft.aufirst=Yu-Ying&rft.date=2004-11-01&rft.volume=80&rft.issue=3&rft.spage=583&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 - 2006-11-29 N1 - Date created - 2004-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lubberts effect in columnar phosphors. AN - 67169332; 15587665 AB - Noise transfer in granular x-ray imaging phosphor screens is not proportional to the square of the magnitude of the signal transfer when the transfer properties are considered for the entire screen thickness, unless appropriately weighted at each depth of interaction. This property, known as the Lubberts effect, has not yet been studied in columnar structured screens because of a lack of a generalized description of the depth-dependent light transport. In this paper, we investigate the signal and noise transfer characteristics of columnar phosphors used in digital mammography detectors using DETECT-II, an optical Monte Carlo light transport simulation code. We first validate our choice of optical parameters for the description of granular and columnar screens using published normalized modulation transfer (MTF) experimental data. Our calculations of MTF match empirically measured MTFs for a granular film/screen analog system, and for an indirect x-ray digital imaging system with CsI:Tl screen representative of digital mammography systems. Using the depth-dependent spread functions and collection efficiencies, we calculate the signal and noise transfer functions and the Lubberts fraction, which is the ratio of the signal transfer function to the noise transfer function, for different screen thicknesses of granular and columnar phosphors. We find that the Lubberts fraction of a 85 microm granular screen model corresponding to a Gd2O2S:Tb screen is similar to the fraction for a 100 microm columnar CsI:Tl screen. JF - Medical physics AU - Badano, Aldo AU - Gagne, Robert M AU - Gallas, Brandon D AU - Jennings, Robert J AU - Boswell, Jonathan S AU - Myers, Kyle J AD - Laboratory for the Assessment of Medical Imaging Systems, Center for Devices and Radiological Health (FDA) and National Institute of Biomedical Imaging and Bioengineering (NIH), Rockville, Maryland 20857, USA. aldo.badano@fda.hhs.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 3122 EP - 3131 VL - 31 IS - 11 SN - 0094-2405, 0094-2405 KW - Phosphorus KW - 27YLU75U4W KW - Index Medicus KW - Sensitivity and Specificity KW - Radiation Dosage KW - Computer Simulation KW - Reproducibility of Results KW - Radiometry -- instrumentation KW - Equipment Failure Analysis -- methods KW - X-Ray Intensifying Screens KW - Radiographic Image Enhancement -- instrumentation KW - Phosphorus -- radiation effects KW - Radiographic Image Enhancement -- methods KW - Radiometry -- methods KW - Models, Theoretical UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67169332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+physics&rft.atitle=Lubberts+effect+in+columnar+phosphors.&rft.au=Badano%2C+Aldo%3BGagne%2C+Robert+M%3BGallas%2C+Brandon+D%3BJennings%2C+Robert+J%3BBoswell%2C+Jonathan+S%3BMyers%2C+Kyle+J&rft.aulast=Badano&rft.aufirst=Aldo&rft.date=2004-11-01&rft.volume=31&rft.issue=11&rft.spage=3122&rft.isbn=&rft.btitle=&rft.title=Medical+physics&rft.issn=00942405&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-31 N1 - Date created - 2004-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rabies encephalitis following fox bite--histological and immunohistochemical evaluation of lesions caused by virus. AN - 67153261; 15584211 AB - Rabies caused by fox bite is uncommon, most cases being caused by bite of rabid dogs (95%). We report a 45-year-old lady with rabies encephalomyelitis caused by bite of a rabid wild fox (Vulpes vulpes), a species prevalent in the Deccan plateaus of Central India. Though foxes are known to be susceptible to rabies, literature on the pathological changes caused by fox bite rabies in humans is scarce. Unlike the mild histological alterations described in canine rabies, a florid encephalitic process evolved in fox bite rabies, in our case, with intense microglial reaction, neuronophagia and perivascular inflammatory infiltrates despite clinical manifestation as a paralytic rabies. Immunostaining using polyclonal antibodies to the rabies viral nucleocapsid antigen and to the whole virion demonstrated high viral load within neurons with extensive spread along dendritic arborization and axonal tracts. Genomic sequence analysis demonstrated close homology with canine virus strain with only minor variations. JF - Clinical neuropathology AU - Suja, M S AU - Mahadevan, A AU - Sundaram, C AU - Mani, J AU - Sagar, B Chandrashekhar AU - Hemachudha, T AU - Wacharapluesadee, S AU - Madhusudana, S N AU - Shankar, S K AD - Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore, India. PY - 2004 SP - 271 EP - 276 VL - 23 IS - 6 SN - 0722-5091, 0722-5091 KW - Index Medicus KW - Microscopy, Electron, Transmission KW - Animals KW - Neurons -- metabolism KW - Humans KW - Middle Aged KW - Animals, Wild -- virology KW - Microscopy, Immunoelectron KW - Neurons -- ultrastructure KW - Immunohistochemistry KW - Female KW - Neurons -- pathology KW - Foxes -- virology KW - Brain -- pathology KW - Rabies -- pathology KW - Rabies -- complications KW - Brain -- metabolism KW - Bites and Stings KW - Encephalitis, Viral -- pathology KW - Brain -- ultrastructure KW - Encephalitis, Viral -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67153261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+neuropathology&rft.atitle=Rabies+encephalitis+following+fox+bite--histological+and+immunohistochemical+evaluation+of+lesions+caused+by+virus.&rft.au=Suja%2C+M+S%3BMahadevan%2C+A%3BSundaram%2C+C%3BMani%2C+J%3BSagar%2C+B+Chandrashekhar%3BHemachudha%2C+T%3BWacharapluesadee%2C+S%3BMadhusudana%2C+S+N%3BShankar%2C+S+K&rft.aulast=Suja&rft.aufirst=M&rft.date=2004-11-01&rft.volume=23&rft.issue=6&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Clinical+neuropathology&rft.issn=07225091&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-28 N1 - Date created - 2004-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicoproteomics: proteomics applied to toxicology and pathology. AN - 67150520; 15580702 AB - Global measurement of proteins and their many attributes in tissues and biofluids defines the field of proteomics. Toxicoproteomics, as part of the larger field of toxicogenomics. seeks to identify critical proteins and pathways in biological systems that are affected by and respond to adverse chemical and environmental exposures using global protein expression technologies. Toxicoproteomics integrates 3 disciplinary areas: traditional toxicology and pathology, differential protein and gene expression analysis, and systems biology. Key topics to be reviewed are the evolution of proteomics, proteomic technology platforms and their capabilities with exemplary studies from biology and medicine, a review of over 50 recent studies applying proteomic analysis to toxicological research, and the recent development of databases designed to integrate -Omics technologies with toxicology and pathology. Proteomics is examined for its potential in discovery of new biomarkers and toxicity signatures, in mapping serum,plasma. and other biofluid proteomes, and in parallel proteomic and transcriptomic studies. The new field of toxicoproteomics is uniquely positioned toward an expanded understanding of protein expression during toxicity and environmental disease for the advancement of public health. JF - Toxicologic pathology AU - Wetmore, Barbara A AU - Merrick, B Alex AD - National Center for Toxicogenomics, National Institute of Environmental Health Sciences, Research Triangle Park, North Caroline 27709, USA. PY - 2004 SP - 619 EP - 642 VL - 32 IS - 6 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Mass Spectrometry KW - Animals KW - Humans KW - Electrophoresis, Gel, Two-Dimensional KW - Chromatography, Liquid KW - Pathology KW - Proteomics KW - Toxicology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67150520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Toxicoproteomics%3A+proteomics+applied+to+toxicology+and+pathology.&rft.au=Wetmore%2C+Barbara+A%3BMerrick%2C+B+Alex&rft.aulast=Wetmore&rft.aufirst=Barbara&rft.date=2004-11-01&rft.volume=32&rft.issue=6&rft.spage=619&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 - 2005-03-10 N1 - Date created - 2004-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Killing the messenger: antisense DNA and siRNA. AN - 67147379; 15578949 AB - Among the technologies available for gene knockdown RNase H-dependent antisense oligonucleotides and RNAi are very popular. Both offer specificity and efficient knockdown of the genes; both are useful tools to study gene functions. Antisense and RNAi methods share many practical problems such as site selection, toxicity at high concentration, and the difficulty of transfection in certain cell types. We will focus in this review on the most important issues in the development of both methods and their possible use in gene-silencing therapy. JF - Current drug targets AU - Nesterova, M AU - Cho-Chung, Y S AD - Cellular Biochem. Section, BRL, CCR, National Cancer Institute, Head, NIH Therapeutic Oligo. Int. Group, Bldg. 10, Rm. 5B05, 9000 Rockville Pike, Bethesda, MD 20892-1750, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 683 EP - 689 VL - 5 IS - 8 SN - 1389-4501, 1389-4501 KW - DNA, Antisense KW - 0 KW - RNA, Small Interfering KW - Index Medicus KW - Gene Silencing KW - Humans KW - DNA, Antisense -- therapeutic use KW - RNA, Small Interfering -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67147379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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&rft.atitle=Killing+the+messenger%3A+antisense+DNA+and+siRNA.&rft.au=Nesterova%2C+M%3BCho-Chung%2C+Y+S&rft.aulast=Nesterova&rft.aufirst=M&rft.date=2004-11-01&rft.volume=5&rft.issue=8&rft.spage=683&rft.isbn=&rft.btitle=&rft.title=Current+drug+targets&rft.issn=13894501&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-27 N1 - Date created - 2004-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distinct incidence patterns among in situ and invasive breast carcinomas,with possible etiologic implications. AN - 67107332; 15564798 AB - Incidence patterns are well-established for invasive breast carcinoma (InvBC) overall and for InvBC defined by estrogen receptor (ER) expression, but are not as well-defined for breast carcinoma in situ (CIS). We, therefore, examined and compared the incidence patterns for CIS and InvBC in the SEER program to define these patterns and to generate etiologic hypotheses. Data were stratified by age or =50 years to approximate menopause. During the years 1973-2000, annual age-adjusted incidence rates rose 660% for CIS and 36% for InvBC, with the most rapid increases occurring in women age > or =50 years. Age-specific incidence rate curves for CIS increased until age 50 years, and then flattened, irrespective of ER expression. On the other hand, rates for InvBC overall and for InvBC defined by ER-positive expression increased continuously with aging, whereas rates for InvBC defined by ER-negative expression flattened after 50 years. Age frequency distribution for CIS and for ER-negative InvBC demonstrated bimodal populations, with a predominant early onset peak incidence at age 50 years. Age frequency distribution for ER-positive InvBC showed bimodal populations with a predominant late-onset mode at age 71 years. Over the last three decades, age-adjusted incidence trends differed for CIS and InvBC in the United States, possibly due to screening mammography and/or etiologic diversity. Indeed, age-specific incidence patterns suggested that carcinogenic events operating early in reproductive life had greater impact upon CIS and InvBC defined by ER-negative expression than upon InvBC overall and InvBC defined by ER-positive expression. JF - Breast cancer research and treatment AU - Anderson, William F AU - Chu, Kenneth C AU - Devesa, Susan S AD - DHHS/NIH/NCI/Division of Cancer Prevention, EPN, Suite 2141, 6130 Executive Boulevard, Bethesda, MD 20892, USA. wanders@mail.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 149 EP - 159 VL - 88 IS - 2 SN - 0167-6806, 0167-6806 KW - Receptors, Estrogen KW - 0 KW - Index Medicus KW - Mammography -- utilization KW - Age Factors KW - Receptors, Estrogen -- biosynthesis KW - Age of Onset KW - Humans KW - Adult KW - Mass Screening -- utilization KW - Incidence KW - Aged KW - Receptors, Estrogen -- analysis KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Neoplasm Invasiveness KW - Carcinoma, Intraductal, Noninfiltrating -- pathology KW - Breast Neoplasms -- pathology KW - Breast Neoplasms -- etiology KW - Carcinoma, Intraductal, Noninfiltrating -- epidemiology KW - Breast Neoplasms -- epidemiology KW - SEER Program -- statistics & numerical data KW - Carcinoma, Intraductal, Noninfiltrating -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67107332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Distinct+incidence+patterns+among+in+situ+and+invasive+breast+carcinomas%2Cwith+possible+etiologic+implications.&rft.au=Anderson%2C+William+F%3BChu%2C+Kenneth+C%3BDevesa%2C+Susan+S&rft.aulast=Anderson&rft.aufirst=William&rft.date=2004-11-01&rft.volume=88&rft.issue=2&rft.spage=149&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 - 2005-03-15 N1 - Date created - 2004-11-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The risk of a mosquito-borne infection in a heterogeneous environment. AN - 67089299; 15510228 AB - A common assumption about malaria, dengue, and other mosquito-borne infections is that the two main components of the risk of human infection--the rate at which people are bitten (human biting rate) and the proportion of mosquitoes that are infectious--are positively correlated. In fact, these two risk factors are generated by different processes and may be negatively correlated across space and time in heterogeneous environments. Uneven distribution of blood-meal hosts and larval habitat creates a spatial mosaic of demograPhic sources and sinks. Moreover, mosquito populations fluctuate temporally, forced by environmental variables such as rainfall, temperature, and humidity. These sources of spatial and temporal heterogeneity in the distribution of mosquito populations generate variability in the human biting rate, in the proportion of mosquitoes that are infectious, and in the risk of human infection. To understand how heterogeneity affects the epidemiology of mosquito-borne infections, we developed a set of simple models that incorporate heterogeneity in a stepwise fashion. These models predict that the human biting rate is highest shortly after the mosquito densities peak, near breeding sites where adult mosquitoes emerge, and around the edges of areas where humans are aggregated. In contrast, the proportion of mosquitoes that are infectious reflects the age structure of mosquito populations; it peaks where old mosquitoes are found, far from mosquito breeding habitat, and when mosquito population density is declining. Finally, we show that estimates for the average risk of infection that are based on the average entomological inoculation rate are strongly biased in heterogeneous environments. JF - PLoS biology AU - Smith, David L AU - Dushoff, Jonathan AU - McKenzie, F Ellis AD - Fogarty International Center, National Institutes of Health, Bethesda, Maryland, USA. smitdave@mail.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 1 VL - 2 IS - 11 KW - Index Medicus KW - Environment KW - Sensitivity and Specificity KW - Weather KW - Animals KW - Larva KW - Humans KW - Population Dynamics KW - Temperature KW - Population Density KW - Risk Factors KW - Seasons KW - Time Factors KW - Models, Theoretical KW - Communicable Diseases -- parasitology KW - Insect Vectors KW - Communicable Diseases -- epidemiology KW - Culicidae -- parasitology KW - Insect Bites and Stings -- epidemiology KW - Communicable Diseases -- transmission UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67089299?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=PLoS+biology&rft.atitle=The+risk+of+a+mosquito-borne+infection+in+a+heterogeneous+environment.&rft.au=Smith%2C+David+L%3BDushoff%2C+Jonathan%3BMcKenzie%2C+F+Ellis&rft.aulast=Smith&rft.aufirst=David&rft.date=2004-11-01&rft.volume=2&rft.issue=11&rft.spage=e368&rft.isbn=&rft.btitle=&rft.title=PLoS+biology&rft.issn=1545-7885&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-02-03 N1 - Date created - 2004-11-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Entomol. 1999;44:131-57 [9990718] J Med Entomol. 1997 Mar;34(2):193-205 [9103763] Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):338-42 [8990210] Trends Ecol Evol. 1999 Sep;14(9):361-366 [10441312] Am J Trop Med Hyg. 1997 Jan;56(1):99-106 [9063370] Parasitology. 1991 Apr;102 Pt 2:167-77 [1852484] Trans R Soc Trop Med Hyg. 1998 Jul-Aug;92(4):381-5 [9850385] J Med Entomol. 1998 Jul;35(4):435-45 [9701925] Trans R Soc Trop Med Hyg. 2002 Mar-Apr;96(2):113-6 [12055794] Bull World Health Organ. 1996;74(3):299-305 [8789928] Trans R Soc Trop Med Hyg. 2002 Sep-Oct;96(5):499-506 [12474476] Am J Trop Med Hyg. 2003 Mar;68(3):357-65 [12685645] Lancet Infect Dis. 2003 May;3(5):297-303 [12726980] Popul Bull UN. 1988;(25):6-26 [12342009] Am J Trop Med Hyg. 2003 Feb;68(2):177-81 [12641408] Am J Trop Med Hyg. 2002 Jul;67(1):32-8 [12363061] Ecol Appl. 1994 Feb;4(1):81-90 [11539870] Annu Rev Microbiol. 1987;41:677-701 [3318682] Malar J. 2002 Dec 6;1:17 [12513703] Trends Parasitol. 2001 Dec;17(12):578-81 [11756041] Am J Trop Med Hyg. 1999 Oct;61(4):513-7 [10548282] Parasitol Today. 2000 Dec;16(12):511-6 [11121847] Am J Trop Med Hyg. 1992 Aug;47(2):181-9 [1354414] Trans R Soc Trop Med Hyg. 1989;83 Suppl:25-9 [2576161] Med Vet Entomol. 2000 Jun;14(2):171-80 [10872861] Am J Trop Med Hyg. 2000 May;62(5):535-44 [11289661] Nature. 2002 Feb 7;415(6872):710-5 [11832960] Am J Trop Med Hyg. 2003 Sep;69(3):244-6 [14628938] Int J Parasitol. 2002 Dec 4;32(13):1617-24 [12435446] J Am Mosq Control Assoc. 1985 Sep;1(3):328-48 [2906674] Am J Trop Med Hyg. 2000 May;62(5):545-51 [11289662] Nature. 1984 Jul 19-25;310(5974):224-5 [6462207] Parasitol Today. 1987 Aug;3(8):231-2 [15462964] Trans R Soc Trop Med Hyg. 1986;80(1):69-77 [3727001] Int J Epidemiol. 2003 Apr;32(2):280-5 [12714550] Trans R Soc Trop Med Hyg. 2000 Jan-Feb;94(1):17-21 [10748890] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A perspective on the new mechanism of antidepressants: neuritogenesis through sigma-1 receptors. AN - 67086991; 15547787 AB - Sigma receptors were first described as one of the opiate receptor subtypes. Now it is well established that sigma receptors, existing as subtypes sigma-1 and sigma-2, are unique non-opioid receptors which are implicated in higher-ordered brain functions. Sigma-1 receptors have high to moderate affinities for (+)benzomorphans and also many psychotrophic drugs and neurosteroids. Sigma-1 receptor agonists and certain neurosteroids such as dehydroepiandrosterone sulfate (DHEA-S) have antidepressant-like effects in animal behavioral models of depression. The antidepressant-like effect induced by sigma-1 receptor agonists may involve intracellular Ca (2+) mobilization such that sigma-1 receptor agonists modulate Ca (2+) release from endoplasmic reticulum (ER) in a cytoskeletal protein-dependent manner. In addition, growth factor-induced neurite outgrowth is mediated through sigma-1 receptors, suggesting a role of antidepressants in neuroplasticity. Igmesine (JO1783), OPC-14 523 and SA4503, have recently been developed as sigma-1 agonists and are found to have antidepressant-like activity perhaps with fewer side effects. This article reviews the new potential use of sigma-1 receptor ligands in the treatment of mood disorder. JF - Pharmacopsychiatry AU - Takebayashi, M AU - Hayashi, T AU - Su, T-P AD - Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, National Institute on Drug Abuse, NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - S208 EP - S213 VL - 37 Suppl 3 SN - 0176-3679, 0176-3679 KW - Antidepressive Agents KW - 0 KW - Receptors, sigma KW - Steroids KW - sigma-1 receptor KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Endoplasmic Reticulum -- metabolism KW - Calcium -- metabolism KW - Animals KW - Drug Interactions KW - Mental Disorders -- drug therapy KW - Humans KW - Binding Sites -- drug effects KW - Steroids -- pharmacokinetics KW - Disease Models, Animal KW - Endoplasmic Reticulum -- drug effects KW - Antidepressive Agents -- pharmacology KW - Receptors, sigma -- physiology KW - Depression -- drug therapy KW - Antidepressive Agents -- therapeutic use KW - Receptors, sigma -- agonists UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67086991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacopsychiatry&rft.atitle=A+perspective+on+the+new+mechanism+of+antidepressants%3A+neuritogenesis+through+sigma-1+receptors.&rft.au=Takebayashi%2C+M%3BHayashi%2C+T%3BSu%2C+T-P&rft.aulast=Takebayashi&rft.aufirst=M&rft.date=2004-11-01&rft.volume=37+Suppl+3&rft.issue=&rft.spage=S208&rft.isbn=&rft.btitle=&rft.title=Pharmacopsychiatry&rft.issn=01763679&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-04 N1 - Date created - 2004-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sepsis associated with immunosuppressive medications: an evidence-based review. AN - 67069158; 15542967 AB - In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for sepsis associated with immunosuppressive medications that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. Immunosuppressed patients, by definition, are susceptible to a wider spectrum of infectious agents than immunologically normal patients and, thus, require a broader spectrum antimicrobial regimen when they present with sepsis or septic shock. Special expertise managing immunosuppressed patient populations is needed to predict and establish the correct diagnosis and to choose appropriate empiric and specific agents and maximize the likelihood that patients will survive these microbial challenges. JF - Critical care medicine AU - Gea-Banacloche, Juan C AU - Opal, Steven M AU - Jorgensen, James AU - Carcillo, Joseph A AU - Sepkowitz, Kent A AU - Cordonnier, Catherine AD - National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - S578 EP - S590 VL - 32 IS - 11 Suppl SN - 0090-3493, 0090-3493 KW - Adrenal Cortex Hormones KW - 0 KW - Anti-Bacterial Agents KW - Antibodies, Monoclonal KW - Antifungal Agents KW - Antiviral Agents KW - Immunosuppressive Agents KW - Tumor Necrosis Factor-alpha KW - Immunophilins KW - EC 5.2.1.8 KW - Mycophenolic Acid KW - HU9DX48N0T KW - Abridged Index Medicus KW - Index Medicus KW - Antiviral Agents -- therapeutic use KW - Anti-Bacterial Agents -- therapeutic use KW - Evidence-Based Medicine KW - Hepatitis, Viral, Human -- drug therapy KW - Humans KW - Aspergillosis -- drug therapy KW - Shock, Septic -- etiology KW - Pneumonia -- drug therapy KW - Adrenal Cortex Hormones -- adverse effects KW - Antifungal Agents -- therapeutic use KW - Candidiasis -- drug therapy KW - Practice Guidelines as Topic KW - Consensus Development Conferences as Topic KW - Tumor Necrosis Factor-alpha -- antagonists & inhibitors KW - Immunophilins -- metabolism KW - Immunocompromised Host KW - Antibodies, Monoclonal -- adverse effects KW - Immune Tolerance -- immunology KW - Mycophenolic Acid -- adverse effects KW - Sepsis -- immunology KW - Sepsis -- etiology KW - Sepsis -- drug therapy KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67069158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+care+medicine&rft.atitle=Sepsis+associated+with+immunosuppressive+medications%3A+an+evidence-based+review.&rft.au=Gea-Banacloche%2C+Juan+C%3BOpal%2C+Steven+M%3BJorgensen%2C+James%3BCarcillo%2C+Joseph+A%3BSepkowitz%2C+Kent+A%3BCordonnier%2C+Catherine&rft.aulast=Gea-Banacloche&rft.aufirst=Juan&rft.date=2004-11-01&rft.volume=32&rft.issue=11+Suppl&rft.spage=S578&rft.isbn=&rft.btitle=&rft.title=Critical+care+medicine&rft.issn=00903493&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-04 N1 - Date created - 2004-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Minocycline-induced hyperpigmentation masquerading as alkaptonuria in individuals with joint pain. AN - 67064175; 15529343 AB - Alkaptonuria, a rare autosomal-recessive disorder caused by mutations in the HGD gene and a deficiency of homogentisate 1,2-dioxygenase, is characterized by accumulation of homogentisic acid (HGA), ochronosis, and destruction of connective tissue resulting in joint disease. Certain medications have been reported to cause cutaneous hyperpigmentation resembling that of alkaptonuria. We present 5 such cases. Eighty-eight patients with a possible diagnosis of alkaptonuria were examined at the National Institutes of Health Clinical Center between June 2000 and March 2004. The diagnosis of alkaptonuria was confirmed or ruled out by measurement of HGA in the urine. Five patients with findings consistent with ochronosis, including pigmentary changes of the ear and mild degenerative disease of the spine and large joints, were diagnosed clinically as having alkaptonuria, but the diagnosis was withdrawn based on normal urine HGA levels. All 5 patients were women who had taken minocycline for dermatologic or rheumatologic disorders for extended periods. Minocycline-induced hyperpigmentation should be considered in the differential diagnosis of ochronosis. This could be of increased significance now that minocycline and other tetracyclines have been proposed as therapeutic options for rheumatoid arthritis, bringing a new population of patients with ochronosis and arthritis to medical attention with the potential, but incorrect, diagnosis of alkaptonuria. JF - Arthritis and rheumatism AU - Suwannarat, Pim AU - Phornphutkul, Chanika AU - Bernardini, Isa AU - Turner, Maria AU - Gahl, William A AD - Section on Human Biochemical Genetics, National Human Genome Research Institute, NIH Building 10, 10 Center Drive, Bethesda, MD 20892, USA. suwannar@nhgri.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 3698 EP - 3701 VL - 50 IS - 11 SN - 0004-3591, 0004-3591 KW - Minocycline KW - FYY3R43WGO KW - Abridged Index Medicus KW - Index Medicus KW - Arthritis, Rheumatoid -- drug therapy KW - Abscess -- drug therapy KW - Diagnosis, Differential KW - Acne Vulgaris -- drug therapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Radiography KW - Facial Dermatoses -- drug therapy KW - Arthralgia KW - Female KW - Hyperpigmentation -- diagnostic imaging KW - Hyperpigmentation -- pathology KW - Hyperpigmentation -- diagnosis KW - Alkaptonuria -- diagnosis KW - Minocycline -- adverse effects KW - Hyperpigmentation -- chemically induced KW - Minocycline -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67064175?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=Minocycline-induced+hyperpigmentation+masquerading+as+alkaptonuria+in+individuals+with+joint+pain.&rft.au=Suwannarat%2C+Pim%3BPhornphutkul%2C+Chanika%3BBernardini%2C+Isa%3BTurner%2C+Maria%3BGahl%2C+William+A&rft.aulast=Suwannarat&rft.aufirst=Pim&rft.date=2004-11-01&rft.volume=50&rft.issue=11&rft.spage=3698&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-17 N1 - Date created - 2004-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunization of HLA-A*0201 and/or HLA-DPbeta1*04 patients with metastatic melanoma using epitopes from the NY-ESO-1 antigen. AN - 67062423; 15534491 AB - HLA class I-restricted peptides are often used in peptide vaccine regimens. There is strong evidence that many of these peptides can generate specific CD8 T-cell responses in vivo; however, only occasional objective clinical responses have been reported. To test whether provision of "help" would enhance antitumor immunity, the authors initiated a clinical trial in which patients with metastatic melanoma were immunized against the NY-ESO-1 tumor antigen, using an HLA-A2-restricted peptide (ESO-1:165V), an HLA-DP4-restricted peptide (NY-ESO-1:161-180), or both peptides given concomitantly. The first cohorts received only ESO-1:165V, using three vaccination schedules. Immunologically, most patients developed immune responses to the HLA-A2-restricted native ESO-1 epitope after vaccination. Peptide vaccine given daily for 4 days appeared to induce immunologic responses more rapidly than if given once a week or once every 3 weeks. In contrast, vaccination using the NY-ESO-1:161-180 peptide induced immune responses in only a few patients. Clinically, one patient who received NY-ESO-1:161-180 peptide alone had a partial response lasing 12 months. Concomitant vaccination with the HLA class II-restricted peptide did not alter the immune response to the HLA class I-restricted peptide form NY-ESO-1. However, vaccination with the HLA-A2-restricted epitope generated primarily T cells that did not recognize tumor after in vitro sensitization. This result raises questions about the use of synthetic peptides derived from NY-ESO-1 as a sole form of immunization. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Khong, Hung T AU - Yang, James C AU - Topalian, Suzanne L AU - Sherry, Richard M AU - Mavroukakis, Sharon A AU - White, Donald E AU - Rosenberg, Steven A AD - Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1502, USA. PY - 2004 SP - 472 EP - 477 VL - 27 IS - 6 SN - 1524-9557, 1524-9557 KW - Antigens, Neoplasm KW - 0 KW - CTAG1B protein, human KW - Cancer Vaccines KW - ESO-1:165V peptide, human KW - HLA-A Antigens KW - HLA-A*02:01 antigen KW - HLA-A2 Antigen KW - HLA-DP Antigens KW - HLA-DP beta-Chains KW - HLA-DPw4 antigen KW - Immunodominant Epitopes KW - Interleukin-2 KW - Membrane Proteins KW - NY-ESO-1:161-180 peptide, human KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Immunodominant Epitopes -- immunology KW - Interleukin-2 -- therapeutic use KW - Humans KW - Cohort Studies KW - Interferon-gamma -- immunology KW - T-Lymphocytes -- immunology KW - Male KW - Female KW - HLA-DP Antigens -- therapeutic use KW - Cancer Vaccines -- immunology KW - Membrane Proteins -- immunology KW - Melanoma -- drug therapy KW - HLA-DP Antigens -- immunology KW - HLA-A Antigens -- toxicity KW - Cancer Vaccines -- therapeutic use KW - HLA-A Antigens -- therapeutic use KW - HLA-DP Antigens -- toxicity KW - Melanoma -- immunology KW - HLA-A Antigens -- immunology KW - Antigens, Neoplasm -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67062423?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Immunization+of+HLA-A*0201+and%2For+HLA-DPbeta1*04+patients+with+metastatic+melanoma+using+epitopes+from+the+NY-ESO-1+antigen.&rft.au=Khong%2C+Hung+T%3BYang%2C+James+C%3BTopalian%2C+Suzanne+L%3BSherry%2C+Richard+M%3BMavroukakis%2C+Sharon+A%3BWhite%2C+Donald+E%3BRosenberg%2C+Steven+A&rft.aulast=Khong&rft.aufirst=Hung&rft.date=2004-11-01&rft.volume=27&rft.issue=6&rft.spage=472&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 - 2005-04-18 N1 - Date created - 2004-11-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int J Cancer. 2001 Oct 15;94(2):252-6 [11668506] Nature. 1998 Jun 4;393(6684):474-8 [9624003] J Exp Med. 1998 Jan 19;187(2):265-70 [9432985] Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1914-8 [9050879] J Immunother. 2003 Jul-Aug;26(4):349-56 [12843797] J Clin Invest. 2002 Dec;110(12):1813-22 [12488431] J Immunol. 2002 Jan 15;168(2):951-6 [11777994] Nature. 1998 Jun 4;393(6684):480-3 [9624005] Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3964-9 [11259659] J Immunother. 2001 Jan-Feb;24(1):1-9 [11211143] Curr Opin Immunol. 1998 Oct;10(5):588-94 [9794842] J Exp Med. 1998 Dec 21;188(12):2357-68 [9858522] Immunity. 1999 Mar;10(3):281-7 [10204484] Nat Med. 1998 Mar;4(3):321-7 [9500606] J Exp Med. 1998 Apr 20;187(8):1349-54 [9547346] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - All trans-retinoic acid acts synergistically with hydroxytamoxifen and transforming-growth factor beta to stimulate apoptosis in MCF-7 breast cancer cells. AN - 67059893; 15531727 AB - The anti-estrogen 4-hydroxytamoxifen (TAM) and vitamin A-related compounds, the retinoids, in combination act synergistically to inhibit growth of breast cancer cells in vitro and in vivo. To clarify the mechanism of this synergism, the effect of TAM and all trans-retinoic acid (AT) on proliferation of MCF-7 breast cancer cells was studied in vitro. TAM and AT acted synergistically to cause a time-dependent and dose-dependent inhibition of MCF-7 cell growth. In a temporally related manner, TAM+AT acted synergistically to downregulate Bcl-2 mRNA and Bcl-2 protein expression, and to stimulate apoptosis. TAM and AT each blocked cell cycle progression throughout 7 days of treatment but without any synergistic or additive effect on this process, indicating a selective synergism for apoptosis. The negative growth factor-transforming growth factor beta (TGFbeta) is secreted by these cells and was studied as a potential mediator of the synergistic effects of TAM+AT on apoptosis. TAM+AT acted synergistically to induce a fivefold increase in TGFbeta1 secretion over 72 h. TGFbeta1 alone had no apoptotic effects on these cells; however, TGFbeta1 in combination with AT acted synergistically to inhibit growth, to downregulate Bcl-2 mRNA and Bcl-2 protein expression, and to stimulate apoptosis of these cells in a manner comparable with that noted for TAM+AT. The synergism of both TAM+AT and TGFbeta1+AT for apoptosis was suppressed by estradiol. Co-incubation of TAM+AT with anti-TGFbeta antibody did not block down-regulation of Bcl-2 protein expression or stimulation of apoptosis. The synergistic effects of TAM+AT on apoptosis therefore occur independently of TGFbeta, although TGFbeta may interact with AT in a novel manner to provide another important anti-proliferative mechanism for breast cancer cells. JF - The Journal of endocrinology AU - Danforth, D N AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bldg. 10/Rm 2B42, Bethesda, Maryland 20892, USA. David_Danforth@nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 395 EP - 404 VL - 183 IS - 2 SN - 0022-0795, 0022-0795 KW - Estrogen Receptor Modulators KW - 0 KW - Transforming Growth Factor beta KW - Tamoxifen KW - 094ZI81Y45 KW - afimoxifene KW - 17197F0KYM KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Stimulation, Chemical KW - Cell Proliferation -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Apoptosis -- drug effects KW - Cell Line, Tumor KW - Drug Synergism KW - Time Factors KW - DNA Fragmentation KW - Female KW - Tretinoin -- pharmacology KW - Tamoxifen -- pharmacology KW - Breast Neoplasms -- pathology KW - Breast Neoplasms -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - Tamoxifen -- analogs & derivatives KW - Estrogen Receptor Modulators -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67059893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+endocrinology&rft.atitle=All+trans-retinoic+acid+acts+synergistically+with+hydroxytamoxifen+and+transforming-growth+factor+beta+to+stimulate+apoptosis+in+MCF-7+breast+cancer+cells.&rft.au=Danforth%2C+D+N&rft.aulast=Danforth&rft.aufirst=D&rft.date=2004-11-01&rft.volume=183&rft.issue=2&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+endocrinology&rft.issn=00220795&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-01 N1 - Date created - 2004-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of a novel transcriptional activator and small RNA in post-transcriptional regulation of the glucose phosphoenolpyruvate phosphotransferase system. AN - 67038510; 15522088 AB - RyaA is a small non-coding RNA in Escherichia coli that was identified by its ability to bind tightly to the RNA chaperone Hfq. This study reports the role of RyaA in mediating the cellular response to glucose-specific phosphoenolypyruvate phosphotransferase system (PTS)-dependent phosphosugar stress. Aiba and co-workers have shown that a block in the metabolism of glucose 6-phosphate causes transient growth inhibition and post-transcriptional regulation of ptsG, encoding the glucose-specific PTS transporter. We found that RyaA synthesis was induced by a non-metabolizable glucose phosphate analogue and was necessary for relief of the toxicity of glucose phosphate stress. Expression of RyaA was sufficient to cause a rapid loss of ptsG mRNA, probably reflecting degradation of the message mediated by RyaA:ptsG pairing. The ryaA gene was renamed sgrS, for sugar transport-related sRNA. Expression of sgrS is regulated by a novel transcriptional activator, SgrR (formerly YabN), which has a putative DNA-binding domain and a solute-binding domain similar to those found in certain transport proteins. Our results suggest that under conditions of glucose phosphate accumulation, SgrR activates SgrS synthesis, causing degradation of ptsG mRNA. Decreased ptsG mRNA results in decreased production of glucose transport machinery, thus limiting further accumulation of glucose phosphate. JF - Molecular microbiology AU - Vanderpool, Carin K AU - Gottesman, Susan AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 1076 EP - 1089 VL - 54 IS - 4 SN - 0950-382X, 0950-382X KW - Escherichia coli Proteins KW - 0 KW - RNA, Bacterial KW - Sugar Phosphates KW - Trans-Activators KW - Phosphoenolpyruvate Sugar Phosphotransferase System KW - EC 2.7.1.- KW - phosphoenolpyruvate-glucose phosphotransferase KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Phenotype KW - Sugar Phosphates -- metabolism KW - Promoter Regions, Genetic KW - Glucose -- analogs & derivatives KW - Escherichia coli -- metabolism KW - Base Sequence KW - Sequence Alignment KW - Glucose -- metabolism KW - Molecular Sequence Data KW - Escherichia coli -- genetics KW - Transcription, Genetic KW - RNA Processing, Post-Transcriptional KW - Gene Expression Regulation, Bacterial KW - Trans-Activators -- metabolism KW - Escherichia coli Proteins -- metabolism KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- genetics KW - Trans-Activators -- genetics KW - Phosphoenolpyruvate Sugar Phosphotransferase System -- metabolism KW - RNA, Bacterial -- metabolism KW - Escherichia coli Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67038510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+microbiology&rft.atitle=Involvement+of+a+novel+transcriptional+activator+and+small+RNA+in+post-transcriptional+regulation+of+the+glucose+phosphoenolpyruvate+phosphotransferase+system.&rft.au=Vanderpool%2C+Carin+K%3BGottesman%2C+Susan&rft.aulast=Vanderpool&rft.aufirst=Carin&rft.date=2004-11-01&rft.volume=54&rft.issue=4&rft.spage=1076&rft.isbn=&rft.btitle=&rft.title=Molecular+microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-08-16 N1 - Date created - 2004-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo imaging detects a transient increase in brain arachidonic acid metabolism: a potential marker of neuroinflammation. AN - 67035934; 15525347 AB - In a rat model of neuroinflammation produced by an intracerebral ventricular infusion of bacterial lipopolysaccaride (LPS), we measured the coefficients of incorporation (k*) of arachidonic acid (AA, 20 : 4n-6) from plasma into each of 80 brain regions, using quantitative autoradiography and intravenously injected [1-(14)C]AA. Compared with control rats infused with artificial cerebrospinal fluid (aCSF), k* was increased significantly in 25 brain areas, many of them close to the CSF compartments, following 6-days of LPS infusion. The increases, ranging from 31 to 76%, occurred in frontal, motor, somatosensory, and olfactory cortex, thalamus, hypothalamus, and septal nuclei, and basal ganglia. Following 28 days of LPS infusion, k* was increased significantly in only two brain regions. Direct analyses of microwaved brain showed that 93 +/- 3 (SD) and 94 +/- 4% of brain radioactivity was in the organic extract as radiolabeled AA in the 6-day control and LPS-infused animals, respectively, compared with 91 +/- 3 and 87 +/- 6% in the 28-day control and LPS-infused animals. These results confirm that brain AA metabolism is disturbed after 6 days of LPS exposure, show this increase is transient, and that these changes can be detected and localized using in vivo imaging with radiolabeled AA. JF - Journal of neurochemistry AU - Lee, Helen AU - Villacreses, Nelly E AU - Rapoport, Stanley I AU - Rosenberger, Thad A AD - Brain Physiology and Metabolism Section, National Institutes on Aging, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 936 EP - 945 VL - 91 IS - 4 SN - 0022-3042, 0022-3042 KW - Biomarkers KW - 0 KW - Carbon Radioisotopes KW - Lipids KW - Arachidonic Acid KW - 27YG812J1I KW - Index Medicus KW - Lipids -- blood KW - Animals KW - Injections, Intravenous KW - Brain Chemistry KW - Disease Progression KW - Disease Models, Animal KW - Autoradiography KW - Injections, Intraventricular KW - Lipids -- analysis KW - Rats KW - Biomarkers -- metabolism KW - Time Factors KW - Lipid Metabolism KW - Brain -- drug effects KW - Arachidonic Acid -- pharmacokinetics KW - Brain -- metabolism KW - Encephalitis -- chemically induced KW - Encephalitis -- metabolism KW - Arachidonic Acid -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67035934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=In+vivo+imaging+detects+a+transient+increase+in+brain+arachidonic+acid+metabolism%3A+a+potential+marker+of+neuroinflammation.&rft.au=Lee%2C+Helen%3BVillacreses%2C+Nelly+E%3BRapoport%2C+Stanley+I%3BRosenberger%2C+Thad+A&rft.aulast=Lee&rft.aufirst=Helen&rft.date=2004-11-01&rft.volume=91&rft.issue=4&rft.spage=936&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 - 2005-05-25 N1 - Date created - 2004-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA methylation, cancer susceptibility, and nutrient interactions. AN - 67035226; 15522834 AB - DNA methylation is an important epigenetic mechanism of transcriptional control. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of cancer. Aberrant methylation of DNA (global hypomethylation accompanied by region-specific hypermethylation) is frequently found in tumor cells. Global hypomethylation can result in chromosome instability, and hypermethylation has been associated with the inaction of tumor suppressor genes. Preclinical and clinical studies suggest that part of the cancer-protective effects associated with several bioactive food components may relate to DNA methylation patterns. Dietary factors that are involved in one-carbon metabolism provide the most compelling data for the interaction of nutrients and DNA methylation because they influence the supply of methyl groups, and therefore the biochemical pathways of methylation processes. These nutrients include folate, vitamin B(12), vitamin B(6), methionine, and choline. However, looking at individual nutrients may be too simplistic. Dietary methyl (folate, choline, and methionine) deficiency in combination causes decreased tissue S-adeno-sylmethionine, global DNA hypomethylation, hepatic steatosis, cirrhosis, and ultimately hepatic tumorigenesis in rodents in the absence of carcinogen treatment. Other dietary components such as vitamin B(12), alcohol, and selenium may modify the response to inadequate dietary folate. JF - Experimental biology and medicine (Maywood, N.J.) AU - Davis, Cindy D AU - Uthus, Eric O AD - Nutritional Sciences Research Group, Division of Cancer Prevention, National Cancer Institute, 6130 Executive Boulevard, Suite 3159, Rockville, MD 20892-7328, USA. davisci@mail.nih.gov. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 988 EP - 995 VL - 229 IS - 10 SN - 1535-3702, 1535-3702 KW - Folic Acid KW - 935E97BOY8 KW - Methionine KW - AE28F7PNPL KW - Selenium KW - H6241UJ22B KW - Index Medicus KW - Animals KW - Folic Acid Deficiency -- pathology KW - Disease Susceptibility KW - Humans KW - Methionine -- metabolism KW - Choline Deficiency -- metabolism KW - Folic Acid -- administration & dosage KW - Selenium -- deficiency KW - Deficiency Diseases -- metabolism KW - Folic Acid Deficiency -- metabolism KW - Deficiency Diseases -- pathology KW - Deficiency Diseases -- genetics KW - Methionine -- deficiency KW - Choline Deficiency -- pathology KW - Selenium -- administration & dosage KW - DNA Methylation KW - Diet KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67035226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+biology+and+medicine+%28Maywood%2C+N.J.%29&rft.atitle=DNA+methylation%2C+cancer+susceptibility%2C+and+nutrient+interactions.&rft.au=Davis%2C+Cindy+D%3BUthus%2C+Eric+O&rft.aulast=Davis&rft.aufirst=Cindy&rft.date=2004-11-01&rft.volume=229&rft.issue=10&rft.spage=988&rft.isbn=&rft.btitle=&rft.title=Experimental+biology+and+medicine+%28Maywood%2C+N.J.%29&rft.issn=15353702&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-19 N1 - Date created - 2004-11-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vitamin E down-modulates iNOS and NADPH oxidase in c-Myc/TGF-alpha transgenic mouse model of liver cancer. AN - 67034042; 15519655 AB - Co-expression of c-Myc and TGF-alpha in the mouse liver accelerates hepatocarcinogenesis and enhances DNA damage due to chronic oxidative stress. Dietary supplementation with vitamin E (VE) inhibits hepatocarcinogenesis and reduces chromosomal alterations in the same mice. Here we investigated the sources of reactive oxygen species (ROS) production in c-Myc/TGF-alpha transgenic mice. Inducible nitric oxide synthase (iNOS) and NADPH oxidase levels were determined in c-Myc, TGF-alpha and c-Myc/TGF-alpha mice by RT-PCR, western blot analysis and immunohistochemistry. iNOS and nitrotyrosines levels were higher in the three transgenic lines when compared with wild-type mice. Preneoplastic and neoplastic lesions from c-Myc, TGF-alpha and c-Myc/TGF-alpha transgenic mice displayed upregulation of NADPH oxidase subunits p47-, 67-phox, Rac1, HSP 70, and HO-1. Importantly, dietary supplementation with vitamin E abolished iNOS expression, lowered nitrotyrosines, p47-, p67-phox, and Rac1 levels, and suppressed HSP 70 and HO-1 proteins in c-Myc/TGF-alpha livers. The results suggest that iNOS and NADPH oxidase are involved in ROS generation during c-Myc/TGF-alpha hepatocarcinogenesis and are inhibited by VE treatment. The data provide additional evidence for the potential use of VE in treatment of chronic liver diseases and HCC prevention. JF - Journal of hepatology AU - Calvisi, Diego F AU - Ladu, Sara AU - Hironaka, Koji AU - Factor, Valentina M AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 4146A1, 37 Convent Drive MSC 4262, Bethesda, MD 20892-4258, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 815 EP - 822 VL - 41 IS - 5 SN - 0168-8278, 0168-8278 KW - Antioxidants KW - 0 KW - HSP70 Heat-Shock Proteins KW - Membrane Proteins KW - Proto-Oncogene Proteins c-myc KW - Transforming Growth Factor alpha KW - Vitamin E KW - 1406-18-4 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 - Heme Oxygenase (Decyclizing) KW - EC 1.14.14.18 KW - Heme Oxygenase-1 KW - Hmox1 protein, mouse KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Index Medicus KW - HSP70 Heat-Shock Proteins -- metabolism KW - Animals KW - Heme Oxygenase (Decyclizing) -- metabolism KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Male KW - NADPH Oxidase -- metabolism KW - Liver Neoplasms -- metabolism KW - Liver Neoplasms -- prevention & control KW - Transforming Growth Factor alpha -- genetics KW - Antioxidants -- pharmacology KW - Liver Neoplasms -- drug therapy KW - Vitamin E -- pharmacology KW - Proto-Oncogene Proteins c-myc -- genetics KW - Tyrosine -- metabolism KW - Tyrosine -- analogs & derivatives KW - Nitric Oxide Synthase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67034042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+hepatology&rft.atitle=Vitamin+E+down-modulates+iNOS+and+NADPH+oxidase+in+c-Myc%2FTGF-alpha+transgenic+mouse+model+of+liver+cancer.&rft.au=Calvisi%2C+Diego+F%3BLadu%2C+Sara%3BHironaka%2C+Koji%3BFactor%2C+Valentina+M%3BThorgeirsson%2C+Snorri+S&rft.aulast=Calvisi&rft.aufirst=Diego&rft.date=2004-11-01&rft.volume=41&rft.issue=5&rft.spage=815&rft.isbn=&rft.btitle=&rft.title=Journal+of+hepatology&rft.issn=01688278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-15 N1 - Date created - 2004-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction between serotonin transporter gene variation and rearing condition in alcohol preference and consumption in female primates. AN - 67031948; 15520362 AB - Serotonin neurotransmission and limbic-hypothalamic-pituitary-adrenal (LHPA) axis hormones are thought to be involved in the reinforcement of alcohol intake and contribute to the risk for alcoholism. In humans and macaques, a promoter polymorphism that decreases transcription of the serotonin transporter gene is associated with anxiety and altered LHPA-axis responses to stress, and in female macaques, exposure to early-life stress alters LHPA-axis activation in response to alcohol. We wanted to determine whether serotonin transporter gene promoter variation (rh-5HTTLPR) and rearing condition would interact to influence alcohol preference in female rhesus macaques. Because of the involvement of stress and LHPA-axis activity in symptoms of withdrawal and relapse, we also wanted to determine whether serotonin transporter gene variation and rearing condition would influence changes in the patterns of alcohol consumption across a 6-week alcohol consumption paradigm. Female macaques were reared with their mothers in social groups (n = 18) or in peer-only groups (n = 14). As young adults, they were given access to an aspartame-sweetened 8.4% alcohol solution and vehicle for 1 hour per day, and volumes of consumption of alcoholic and nonalcoholic solutions were recorded. Serotonin transporter genotype (l/l and l/s) was determined using polymerase chain reaction followed by gel electrophoresis. We found interactions between rearing condition and serotonin transporter genotype, such that l/s peer-reared females demonstrated higher levels of ethanol preference. We also found an effect of rearing condition on the percentage change in alcohol consumed during the 6 weeks as well as a phase by rearing interaction, such that peer-reared animals progressively increased their levels of consumption across the course of the study. This was especially evident for peer-reared females with the l/s rh5-HTTLPR genotype. These data suggest a potential interaction between serotonin transporter gene variation and early experience in vulnerability to alcoholism. JF - Archives of general psychiatry AU - Barr, Christina S AU - Newman, Timothy K AU - Lindell, Stephen AU - Shannon, Courtney AU - Champoux, Maribeth AU - Lesch, Klaus Peter AU - Suomi, Stephen J AU - Goldman, David AU - Higley, J Dee AD - National Institute on Alcoholism and Alcohol Abuse, Laboratory of Clinical Studies and National Institute of Child Health and Human Development, Laboratory of Comparative Ethology, National Institutes of Health, Poolesville, MD, USA. cbarr@mail.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 1146 EP - 1152 VL - 61 IS - 11 SN - 0003-990X, 0003-990X KW - Membrane Glycoproteins KW - 0 KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - SLC6A4 protein, human KW - Serotonin Plasma Membrane Transport Proteins KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Sex Factors KW - Animal Husbandry -- methods KW - Polymorphism, Genetic KW - Humans KW - Macaca KW - Reinforcement (Psychology) KW - Disease Models, Animal KW - Alcoholism -- genetics KW - Genotype KW - Genetic Predisposition to Disease -- genetics KW - Promoter Regions, Genetic -- genetics KW - Female KW - Male KW - Social Environment KW - Nerve Tissue Proteins -- physiology KW - Genetic Variation KW - Membrane Glycoproteins -- physiology KW - Stress, Psychological -- genetics KW - Conditioning, Operant -- physiology KW - Membrane Transport Proteins -- physiology KW - Nerve Tissue Proteins -- genetics KW - Animals, Newborn -- genetics KW - Alcohol Drinking -- psychology KW - Behavior, Animal -- physiology KW - Alcohol Drinking -- genetics KW - Animals, Newborn -- growth & development KW - Membrane Transport Proteins -- genetics KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67031948?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Interaction+between+serotonin+transporter+gene+variation+and+rearing+condition+in+alcohol+preference+and+consumption+in+female+primates.&rft.au=Barr%2C+Christina+S%3BNewman%2C+Timothy+K%3BLindell%2C+Stephen%3BShannon%2C+Courtney%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=2004-11-01&rft.volume=61&rft.issue=11&rft.spage=1146&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-24 N1 - Date created - 2004-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evidence of reperfusion injury, exacerbated by thrombolytic therapy, in human focal brain ischemia using a novel imaging marker of early blood-brain barrier disruption. AN - 67030764; 15472105 AB - Loss of integrity of the blood-brain barrier (BBB) resulting from ischemia and reperfusion is a hypothesized precursor to hemorrhagic transformation (HT) and worse clinical outcome than would be expected from the beneficial effects of reperfusion. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in acute focal brain ischemia and tested associations with reperfusion, HT, and poor outcome (modified Rankin score >2). The BBB disruption was evident as delayed gadolinium enhancement of cerebrospinal fluid space on fluid-attenuated inversion recovery (FLAIR) images and, for convenience, has been termed hyperintense acute reperfusion marker (HARM). HARM was found in 47 of 144 (33%) ischemic stroke patients. Reperfusion was found to be the strongest independent predictor of early BBB disruption (P=0.018) in multivariate analysis. HARM was associated with HT and worse clinical outcome (after adjustment for initial severity). It was also associated with more severe strokes at onset and greater age. Because the timing of the disruption was early enough (median estimate 3.8 hours from onset) to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by HARM may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome. JF - Stroke AU - Warach, Steven AU - Latour, Lawrence L AD - National Institute of Neurological Disorders & Stroke, 10 Center Drive, MSC 1063, Building 10, Room B1D733, Bethesda, MD 20892-1063, USA. warachs@ninds.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 2659 EP - 2661 VL - 35 IS - 11 Suppl 1 KW - Fibrinolytic Agents KW - 0 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Humans KW - Cerebral Hemorrhage -- etiology KW - Brain Ischemia -- drug therapy KW - Reperfusion Injury -- physiopathology KW - Fibrinolytic Agents -- adverse effects KW - Thrombolytic Therapy -- adverse effects KW - Brain Ischemia -- physiopathology KW - Blood-Brain Barrier UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67030764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Evidence+of+reperfusion+injury%2C+exacerbated+by+thrombolytic+therapy%2C+in+human+focal+brain+ischemia+using+a+novel+imaging+marker+of+early+blood-brain+barrier+disruption.&rft.au=Warach%2C+Steven%3BLatour%2C+Lawrence+L&rft.aulast=Warach&rft.aufirst=Steven&rft.date=2004-11-01&rft.volume=35&rft.issue=11+Suppl+1&rft.spage=2659&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 - 2005-05-19 N1 - Date created - 2004-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. AN - 67029048; 15520358 AB - No information is available on the co-occurrence of DSM-IV nicotine dependence and Axis I and II psychiatric disorders in the US population. To present national data on the co-occurrence of current DSM-IV nicotine dependence and other psychiatric disorders by sex and to estimate the burden of all US tobacco consumption carried by nicotine-dependent and psychiatrically ill individuals. Face-to-face interviews. The United States. Household and group-quarters adults (N = 43 093). Prevalence and comorbidity of current nicotine dependence and Axis I and II disorders and the percentage of cigarettes consumed in the United States among psychiatrically vulnerable subgroups. Among US adults, 12.8% (95% confidence interval, 12.0-13.6) were nicotine dependent. Associations between nicotine dependence and specific Axis I and II disorders were all strong and statistically significant (P<.05) in the total population and among men and women. Nicotine-dependent individuals made up only 12.8% (95% confidence interval, 12.0-13.6) of the population yet consumed 57.5% of all cigarettes smoked in the United States. Nicotine-dependent individuals with a comorbid psychiatric disorder made up 7.1% (95% confidence interval, 6.6-7.6) of the population yet consumed 34.2% of all cigarettes smoked in the United States. Nicotine-dependent and psychiatrically ill individuals consume about 70% of all cigarettes smoked in the United States. The results of this study highlight the importance of focusing smoking cessation efforts on individuals who are nicotine dependent, individuals who have psychiatric disorders, and individuals who have comorbid nicotine dependence and other psychiatric disorders. Further, awareness of industry segmentation strategies can improve smoking cessation efforts of clinicians and other health professionals among all smokers and especially among the most vulnerable. JF - Archives of general psychiatry AU - Grant, Bridget F AU - Hasin, Deborah S AU - Chou, S Patricia AU - Stinson, Frederick S AU - Dawson, Deborah A AD - Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. bgrant@willco.niaaa.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 1107 EP - 1115 VL - 61 IS - 11 SN - 0003-990X, 0003-990X KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Diagnosis, Dual (Psychiatry) KW - Smoking -- psychology KW - Smoking -- prevention & control KW - Smoking -- epidemiology KW - Comorbidity KW - Alcohol-Related Disorders -- diagnosis KW - Substance-Related Disorders -- diagnosis KW - Personality Disorders -- epidemiology KW - Personality Disorders -- diagnosis KW - Adult KW - Health Surveys KW - Smoking Cessation -- methods KW - Confidence Intervals KW - Tobacco -- adverse effects KW - Adolescent KW - United States -- epidemiology KW - Female KW - Male KW - Substance-Related Disorders -- epidemiology KW - Prevalence KW - Alcohol-Related Disorders -- epidemiology KW - Mental Disorders -- diagnosis KW - Tobacco Use Disorder -- epidemiology KW - Mental Disorders -- epidemiology KW - Tobacco Use Disorder -- prevention & control KW - Tobacco Use Disorder -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67029048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Nicotine+dependence+and+psychiatric+disorders+in+the+United+States%3A+results+from+the+national+epidemiologic+survey+on+alcohol+and+related+conditions.&rft.au=Grant%2C+Bridget+F%3BHasin%2C+Deborah+S%3BChou%2C+S+Patricia%3BStinson%2C+Frederick+S%3BDawson%2C+Deborah+A&rft.aulast=Grant&rft.aufirst=Bridget&rft.date=2004-11-01&rft.volume=61&rft.issue=11&rft.spage=1107&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-24 N1 - Date created - 2004-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions. AN - 67028474; 15284179 AB - Lung cancer rates among men and particularly among women, almost all of whom are non-smokers, in Xuan Wei County, China are among the highest in China and have been causally associated with exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). As such, this population provides a unique opportunity to study the pathogenesis of PAH-induced lung cancer that is not substantially influenced by the large number of other carcinogenic constituents of tobacco smoke. Aldo-keto reductases (AKRs) activate PAH dihydrodiols to yield their corresponding reactive and redox-active o-quinones, which can then generate reactive oxygen species that cause oxidative DNA damage. We therefore examined the association between single nucleotide polymorphisms (SNPs) in four genes (AKR1C3-Gln5His, NQO1-Pro187Ser, MnSOD-Val16Ala and OGG1-Ser326Cys) that play a role in the generation, prevention or repair of oxidative damage and lung cancer risk in a population-based, case-control study of 119 cases and 113 controls in Xuan Wei, China. The AKR1C3-Gln/Gln genotype was associated with a 1.84-fold [95% confidence interval (CI) = 0.98-3.45] increased risk and the combined OGG1-Cys/Cys and Ser/Cys genotypes were associated with a 1.93-fold (95% CI = 1.12-3.34) increased risk of lung cancer. Subgroup analysis revealed that the effects were particularly elevated among women who had relatively high cumulative exposure to smoky coal. SNPs in MnSOD and NQO1 were not associated with lung cancer risk. These results suggest that SNPs in the oxidative stress related-genes AKR1C3 and OGG1 may play a role in the pathogenesis of lung cancer in this population, particularly among heavily exposed women. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and other populations with substantial exposure to PAHs. JF - Carcinogenesis AU - Lan, Qing AU - Mumford, Judy L AU - Shen, Min AU - Demarini, David M AU - Bonner, Matthew R AU - He, Xingzhou AU - Yeager, Meredith AU - Welch, Robert AU - Chanock, Stephen AU - Tian, Linwei AU - Chapman, Robert S AU - Zheng, Tongzhang AU - Keohavong, Phouthone AU - Caporaso, Neil AU - Rothman, Nathaniel AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892, USA. qingl@mail.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 2177 EP - 2181 VL - 25 IS - 11 SN - 0143-3334, 0143-3334 KW - Coal KW - 0 KW - Polycyclic Aromatic Hydrocarbons KW - 3-Hydroxysteroid Dehydrogenases KW - EC 1.1.- KW - AKR1C3 protein, human KW - EC 1.1.1.- KW - Hydroxyprostaglandin Dehydrogenases KW - DNA Glycosylases KW - EC 3.2.2.- KW - oxoguanine glycosylase 1, human KW - Index Medicus KW - United States KW - Genotype KW - Sex Characteristics KW - Humans KW - Case-Control Studies KW - Smoking -- adverse effects KW - Oxidative Stress -- genetics KW - Middle Aged KW - Mutation KW - Male KW - Female KW - Amino Acid Substitution KW - Occupational Exposure KW - Lung Neoplasms -- prevention & control KW - 3-Hydroxysteroid Dehydrogenases -- genetics KW - Hydroxyprostaglandin Dehydrogenases -- genetics KW - DNA Glycosylases -- genetics KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67028474?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Oxidative+damage-related+genes+AKR1C3+and+OGG1+modulate+risks+for+lung+cancer+due+to+exposure+to+PAH-rich+coal+combustion+emissions.&rft.au=Lan%2C+Qing%3BMumford%2C+Judy+L%3BShen%2C+Min%3BDemarini%2C+David+M%3BBonner%2C+Matthew+R%3BHe%2C+Xingzhou%3BYeager%2C+Meredith%3BWelch%2C+Robert%3BChanock%2C+Stephen%3BTian%2C+Linwei%3BChapman%2C+Robert+S%3BZheng%2C+Tongzhang%3BKeohavong%2C+Phouthone%3BCaporaso%2C+Neil%3BRothman%2C+Nathaniel&rft.aulast=Lan&rft.aufirst=Qing&rft.date=2004-11-01&rft.volume=25&rft.issue=11&rft.spage=2177&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2007-03-12 N1 - Date created - 2004-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutant K-rasV12 increases COX-2, peroxides and DNA damage in lung cells. AN - 67028417; 15284181 AB - K-ras is frequently mutated in lung adenocarcinomas. Recent discovery that wild-type K-ras is tumor suppressive in the lung raises a question: how is mutant K-ras aggressively oncogenic? We hypothesized that mutant K-ras might lead to generation of reactive oxygen species (ROS) and DNA damage, contributing to malignant transformation. We stably transfected human mutant K-ras(V12) into non-transformed peripheral mouse lung epithelial cells (E10 line). Constitutively active mutant K-ras(V12) in E10 cells led to a highly significant (P < 0.001) increased level of peroxides, and a corresponding increase in the amount of DNA strand-break damage, compared with the parental line E10 and the vector control. Levels of superoxide were not increased, suggesting a direct source of peroxides, such as cyclooxygenase-2 (COX-2). COX-2 protein and activity measured as prostaglandin E(2) level were up-regulated in cells expressing mutant K-ras(V12); COX-2 activity correlated with K-ras activity (K-ras p21-GTP). Both peroxide generation and DNA single strand breaks were significantly reduced by pre-treatment with COX-2-specific inhibitor SC 58125, confirming COX-2 as the source of the ROS. COX-2 has been repeatedly implicated in lung cancer, and is known to be regulated by ras and to release ROS. Our data suggest that up-regulation of COX-2, with a consequent increase in peroxides and DNA damage, contributes to the dominant oncogenicity of mutant K-ras. JF - Carcinogenesis AU - Maciag, Anna AU - Sithanandam, Gunamani AU - Anderson, Lucy M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Inc., Frederick, MD 21702, USA. amaciag@mail.ncifcrf.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 2231 EP - 2237 VL - 25 IS - 11 SN - 0143-3334, 0143-3334 KW - Membrane Proteins KW - 0 KW - Peroxides KW - Reactive Oxygen Species KW - Superoxides KW - 11062-77-4 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Index Medicus KW - Animals KW - Superoxides -- metabolism KW - Genetic Vectors KW - Mice KW - Cell Line, Tumor KW - Mice, Inbred BALB C KW - Female KW - Genes, ras KW - Lung Neoplasms -- enzymology KW - Peroxides -- metabolism KW - DNA Damage KW - Membrane Proteins -- metabolism KW - Cyclooxygenase 2 -- metabolism KW - Mutation KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67028417?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Mutant+K-rasV12+increases+COX-2%2C+peroxides+and+DNA+damage+in+lung+cells.&rft.au=Maciag%2C+Anna%3BSithanandam%2C+Gunamani%3BAnderson%2C+Lucy+M&rft.aulast=Maciag&rft.aufirst=Anna&rft.date=2004-11-01&rft.volume=25&rft.issue=11&rft.spage=2231&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2007-03-12 N1 - Date created - 2004-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pathogenesis of hepatitis C-associated hepatocellular carcinoma. AN - 67018830; 15508105 AB - Epidemiologic, clinical, and virologic data have shown a close association between chronic infection with hepatitis C virus (HCV) and the development of hepatocellular carcinoma (HCC). In many countries of the developed world, HCV infection accounts for more than half of the cases of HCC. HCC usually arises after 2-4 decades of infection, typically in the context of an underlying cirrhosis. Treatment of hepatitis C with interferon-alfa can lead to sustained clearance of HCV, and small prospective studies as well as larger retrospective analyses suggest that interferon therapy leads to a decrease in the incidence of HCC. Without a reliable tissue culture system or a small animal model of HCV infection, analysis of the mechanisms by which HCV leads to cancer has been difficult. Nevertheless, both in vitro expression systems and in vivo transgenic mice studies suggest that HCV has an inherent carcinogenic potential. Understanding the pathogenesis of HCV-associated HCC is important in developing effective means of prevention and treatment of this highly malignant form of cancer. JF - Gastroenterology AU - Liang, T Jake AU - Heller, Theo AD - Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. Jakel@intra.niddk.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - S62 EP - S71 VL - 127 IS - 5 Suppl 1 SN - 0016-5085, 0016-5085 KW - Antiviral Agents KW - 0 KW - Interferon-alpha KW - Abridged Index Medicus KW - Index Medicus KW - Antiviral Agents -- therapeutic use KW - Animals KW - Interferon-alpha -- therapeutic use KW - Risk Factors KW - Humans KW - Incidence KW - Disease Models, Animal KW - Mice KW - Mice, Transgenic KW - Cell Transformation, Neoplastic KW - Carcinoma, Hepatocellular -- virology KW - Hepacivirus -- pathogenicity KW - Hepatitis C -- complications KW - Liver Neoplasms -- virology KW - Liver Neoplasms -- physiopathology KW - Liver Neoplasms -- epidemiology KW - Carcinoma, Hepatocellular -- physiopathology KW - Carcinoma, Hepatocellular -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67018830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gastroenterology&rft.atitle=Pathogenesis+of+hepatitis+C-associated+hepatocellular+carcinoma.&rft.au=Liang%2C+T+Jake%3BHeller%2C+Theo&rft.aulast=Liang&rft.aufirst=T&rft.date=2004-11-01&rft.volume=127&rft.issue=5+Suppl+1&rft.spage=S62&rft.isbn=&rft.btitle=&rft.title=Gastroenterology&rft.issn=00165085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-02 N1 - Date created - 2004-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genome-scale profiling of gene expression in hepatocellular carcinoma: classification, survival prediction, and identification of therapeutic targets. AN - 67017473; 15508103 AB - The heterogeneous nature of human hepatocellular carcinoma (HCC) has hampered both treatment and prognostic predictions. Gene expression profiles of human HCC were analyzed to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. By applying global gene expression analyses, including unsupervised and supervised methods, 2 distinctive subclasses of HCC that were highly homogeneous for both the underlying biology and the clinical outcome were discovered. Tumors from the low survival subclass had strong cell proliferation and antiapoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and sumoylation, suggesting an etiologic involvement of these processes in accelerating the progression of HCC. Genes most strongly associated with survival were identified by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provided new molecular insights into the pathogenesis of HCC. Future studies will evaluate potential diagnostic markers and therapeutic targets identified during the global gene expression studies. Furthermore, cross-species similarity of gene expression patterns will also allow prioritization of a long list of genes obtained from human gene expression profiling studies and focus on genes whose expression is altered during tumorigenesis in both species. JF - Gastroenterology AU - Lee, Ju-Seog AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - S51 EP - S55 VL - 127 IS - 5 Suppl 1 SN - 0016-5085, 0016-5085 KW - Biomarkers, Tumor KW - 0 KW - DNA, Neoplasm KW - Abridged Index Medicus KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Humans KW - Prognosis KW - Biomarkers, Tumor -- analysis KW - Cell Proliferation KW - Cell Transformation, Neoplastic KW - Cell Survival KW - Gene Expression Profiling KW - Oligonucleotide Array Sequence Analysis KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- physiopathology KW - DNA, Neoplasm -- analysis KW - Carcinoma, Hepatocellular -- classification KW - Carcinoma, Hepatocellular -- physiopathology KW - Liver Neoplasms -- classification KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67017473?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gastroenterology&rft.atitle=Genome-scale+profiling+of+gene+expression+in+hepatocellular+carcinoma%3A+classification%2C+survival+prediction%2C+and+identification+of+therapeutic+targets.&rft.au=Lee%2C+Ju-Seog%3BThorgeirsson%2C+Snorri+S&rft.aulast=Lee&rft.aufirst=Ju-Seog&rft.date=2004-11-01&rft.volume=127&rft.issue=5+Suppl+1&rft.spage=S51&rft.isbn=&rft.btitle=&rft.title=Gastroenterology&rft.issn=00165085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-02 N1 - Date created - 2004-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel host range and cytopathic variant of ecotropic Friend murine leukemia virus. AN - 67016904; 15507605 AB - A variant ecotropic Friend murine leukemia virus, F-S MLV, is capable of inducing the formation of large multinucleated syncytia in Mus dunni cells. This cytopathicity resembles that of Spl574 MLV, a novel variant recently isolated from the spleen of a Mus spicilegus mouse neonatally inoculated with Moloney MLV. F-S MLV is an N-tropic Friend MLV that also has the unusual ability to infect hamster cells, which are normally resistant to mouse ecotropic MLVs. Syncytium induction by both F-S MLV and Spl574 is accompanied by the accumulation of large amounts of unintegrated viral DNA, a hallmark of pathogenic retroviruses, but not previously reported for mouse ecotropic gammaretroviruses. Sequencing and site-specific mutagenesis determined that the syncytium-inducing phenotype of F-S MLV can be attributed to a single amino acid substitution (S84A) in the VRA region of the viral env gene. This site corresponds to that of the single substitution previously shown to be responsible for the cytopathicity of Spl574, S82F. The S84A substitution in F-S MLV also contributes to the ability of this virus to infect hamster cells, but Spl574 MLV is unable to infect hamster cells. Because this serine residue is one of the critical amino acids that form the CAT-1 receptor binding site, and because M. dunni and hamster cells have variant CAT-1 receptors, these results suggest that syncytium formation as well as altered host range may be a consequence of altered interaction between virus and receptor. JF - Journal of virology AU - Jung, Yong Tae AU - Wu, Tiyun AU - Kozak, Christine A AD - Labotratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases/NIH, Bldg. 4, Room 329, 4 Center Drive, MSC 0460, Bethesda, MD 20892-0460, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 12189 EP - 12197 VL - 78 IS - 22 SN - 0022-538X, 0022-538X KW - DNA, Viral KW - 0 KW - Index Medicus KW - Animals KW - Moloney murine leukemia virus -- pathogenicity KW - Cricetulus KW - Genes, env KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - NIH 3T3 Cells KW - DNA, Viral -- metabolism KW - Cricetinae KW - Cloning, Molecular KW - Friend murine leukemia virus -- pathogenicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67016904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Novel+host+range+and+cytopathic+variant+of+ecotropic+Friend+murine+leukemia+virus.&rft.au=Jung%2C+Yong+Tae%3BWu%2C+Tiyun%3BKozak%2C+Christine+A&rft.aulast=Jung&rft.aufirst=Yong&rft.date=2004-11-01&rft.volume=78&rft.issue=22&rft.spage=12189&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 - 2004-11-23 N1 - Date created - 2004-10-27 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AY563028; GENBANK; AY563029 N1 - SuppNotes - Cited By: J Virol. 1998 Apr;72(4):2686-96 [9525586] Science. 1997 Sep 12;277(5332):1662-6 [9287219] J Virol. 2001 Jul;75(13):6007-15 [11390602] J Virol. 1999 May;73(5):3758-63 [10196270] J Virol. 2003 May;77(9):5065-72 [12692209] J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] Virology. 1970 Dec;42(4):1136-9 [4099080] Genetics. 1972 Oct;72(2):239-52 [4345996] Virology. 1975 May;65(1):128-34 [167514] J Virol. 1980 Jan;33(1):475-86 [6245244] J Virol. 1981 Sep;39(3):713-21 [6270346] Nature. 1981 Oct 15-21;293(5833):543-8 [6169994] J Virol. 1984 Mar;49(3):828-40 [6321768] J Virol. 1984 Jun;50(3):970-3 [6328027] J Virol. 1984 Nov;52(2):695-8 [6092693] Cell. 1986 May 9;45(3):365-74 [3009025] Science. 1988 Apr 1;240(4848):80-2 [2832945] Rev Infect Dis. 1988 Mar-Apr;10(2):399-405 [2836939] J Virol. 1990 Feb;64(2):467-75 [2296075] J Virol. 1991 Nov;65(11):5975-82 [1717711] J Virol. 1992 Jan;66(1):78-84 [1370096] Nucleic Acids Res. 1992 Jun 25;20(12):3249 [1620621] 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 Nov;68(11):7516-24 [7933135] Virology. 1996 Jan 15;215(2):142-51 [8560761] J Virol. 1996 Dec;70(12):8534-9 [8970977] Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13813-8 [12370415] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular mechanisms of primary resistance to flucytosine in Candida albicans. AN - 67004636; 15504867 AB - Primary resistance in Candida albicans to flucytosine (5-FC) was investigated in 25 strains by identifying and sequencing the genes FCA1, FUR1, FCY21, and FCY22, which code for cytosine deaminase, uracil phosphoribosyltransferase (UPRT), and two purine-cytosine permeases, respectively. These proteins are involved in pyrimidine salvage and 5-FC metabolism. An association between a polymorphic nucleotide and resistance to 5-FC was found within FUR1 where the substitution of cytidylate for thymidylate at nucleotide position 301 results in the replacement of arginine with cysteine at amino acid position 101 in UPRT. Isolates that are homozygous for this mutation display increased levels of resistance to 5-FC, whereas heterozygous isolates have reduced susceptibility. Three-dimensional protein modeling of UPRT suggests that the Arg101Cys mutation disturbs the quaternary structure of the enzyme, which is postulated to compromise optimal enzyme activity. A single resistant isolate, lacking the above polymorphism in FUR1, has a homozygous polymorphism in FCA1 that results in a glycine-to-aspartate substitution at position 28 in cytosine deaminase. JF - Antimicrobial agents and chemotherapy AU - Hope, William W AU - Tabernero, Lydia AU - Denning, David W AU - Anderson, Michael J AD - Immunocompromised Host Section POB, NCI, NIH CRC, Room 1-5700, 10 Center Dr., MSC 1100, Bethesda, MD 20892-1100, USA. hopew@mail.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 4377 EP - 4386 VL - 48 IS - 11 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Antimetabolites KW - DNA Primers KW - DNA, Fungal KW - FCY2 protein, S cerevisiae KW - Membrane Transport Proteins KW - Nucleobase Transport Proteins KW - Saccharomyces cerevisiae Proteins KW - Flucytosine KW - D83282DT06 KW - Pentosyltransferases KW - EC 2.4.2.- KW - uracil phosphoribosyltransferase KW - EC 2.4.2.9 KW - Cytosine Deaminase KW - EC 3.5.4.1 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Models, Molecular KW - Polymorphism, Genetic -- genetics KW - Amino Acid Sequence KW - Reverse Transcriptase Polymerase Chain Reaction KW - Antimetabolites -- pharmacology KW - Genes, Fungal -- genetics KW - Drug Resistance, Fungal KW - Pentosyltransferases -- metabolism KW - Molecular Sequence Data KW - Fluorouracil -- pharmacology KW - Cytosine Deaminase -- metabolism KW - DNA, Fungal -- genetics KW - Membrane Transport Proteins -- metabolism KW - Microbial Sensitivity Tests KW - DNA, Fungal -- biosynthesis KW - Flucytosine -- pharmacology KW - Antifungal Agents -- pharmacology KW - Candida albicans -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67004636?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Molecular+mechanisms+of+primary+resistance+to+flucytosine+in+Candida+albicans.&rft.au=Hope%2C+William+W%3BTabernero%2C+Lydia%3BDenning%2C+David+W%3BAnderson%2C+Michael+J&rft.aulast=Hope&rft.aufirst=William&rft.date=2004-11-01&rft.volume=48&rft.issue=11&rft.spage=4377&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 - 2004-12-21 N1 - Date created - 2004-10-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Antimicrob Chemother. 2000 Mar;45(3):408-9 [10702571] Chemotherapy. 1977;23(4):243-59 [324722] Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):78-83 [11773618] Antimicrob Agents Chemother. 2002 Nov;46(11):3518-21 [12384359] J Biol Chem. 2003 May 23;278(21):18990-6 [12649274] Antimicrob Agents Chemother. 2004 Jan;48(1):262-6 [14693548] Antimicrob Agents Chemother. 2004 Jun;48(6):2223-7 [15155225] J Bacteriol. 1970 Jun;102(3):607-15 [5429721] Antimicrob Agents Chemother. 1972 Sep;2(3):114-21 [4597703] J Biol Chem. 1979 Mar 10;254(5):1558-63 [216696] Antimicrob Agents Chemother. 1983 Jan;23(1):79-85 [6338821] J Antimicrob Chemother. 1984 Jul;14(1):1-8 [6480540] Proc Natl Acad Sci U S A. 1984 Oct;81(20):6276-80 [6387700] Antimicrob Agents Chemother. 1984 Oct;26(4):570-4 [6393861] Ann N Y Acad Sci. 1988;544:260-3 [3063172] Gene. 1990 Apr 16;88(2):149-57 [2189783] Mol Microbiol. 1990 Apr;4(4):585-96 [2191181] Curr Genet. 1991 May;19(5):333-7 [1913872] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915-9 [1438297] Comput Appl Biosci. 1996 Aug;12(4):357-8 [8902363] Curr Genet. 1997 Jan;31(1):1-6 [9000374] Protein Expr Purif. 1997 Aug;10(3):356-64 [9268683] EMBO J. 1998 Jun 15;17(12):3219-32 [9628859] Chemotherapy. 1975;21(3-4):113-30 [1098864] J Antimicrob Chemother. 2000 Aug;46(2):171-9 [10933638] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Validated gas chromatographic-negative ion chemical ionization mass spectrometric method for delta(9)-tetrahydrocannabinol in sweat patches. AN - 67002147; 15271860 AB - A sensitive gas chromatography-negative ion chemical ionization mass spectrometry (GC/MS-NICI) method was developed and validated for the measurement of Delta(9)-tetrahydrocannabinol (THC) in human sweat patches. THC-d(0) and THC-d(3) were added to worn blank sweat patches (PharmChek; PharmChem Incorporated) and extracted with 3 mL of methanol-0.2 mol/L sodium acetate buffer (pH 5.0, 3:1 by volume) on a reciprocating shaker at ambient temperature for 30 min. Extracted solution (2 mL) was diluted with 8 mL of 0.1 mol/L sodium acetate buffer (pH 4.5) and extracted by use of solid-phase extraction columns (CleanScreen; United Chemical Technologies). Dried extracts were derivatized with trifluoroacetic acid and analyzed with an Agilent 6890 gas chromatograph interfaced with an Agilent 5973 mass selective detector operated in NICI-selected ion-monitoring mode. The lower limits of detection and quantification for THC in human sweat were 0.2 and 0.4 ng/patch, respectively. The calibration curve was linear from 0.4 to 10 ng/patch (R(2) >0.995). Overall recovery of THC from blank worn patches to which 0.6, 4.0, and 8.0 ng of THC had been added was 44-46%. Assay imprecision, expressed as CV, was <10% for 0.6, 4.0, and 8.0 ng/patch quality-control samples. Twenty-one potential interfering compounds (50 ng/patch) added to low quality-control samples (0.6 ng/patch) did not influence THC quantification. This GC/MS-NICI assay for THC in human sweat provides adequate sensitivity and performance characteristics for analyzing THC in sweat patches and meets the requirements of the proposed Substance Abuse and Mental Health Administration's guidelines for sweat testing. JF - Clinical chemistry AU - Saito, Takeshi AU - Wtsadik, Abraham AU - Scheidweiler, Karl B AU - Fortner, Neil AU - Takeichi, Sanae AU - Huestis, Marilyn A AD - Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 2083 EP - 2090 VL - 50 IS - 11 SN - 0009-9147, 0009-9147 KW - Dronabinol KW - 7J8897W37S KW - Index Medicus KW - Sensitivity and Specificity KW - Reproducibility of Results KW - Humans KW - Marijuana Abuse -- diagnosis KW - Gas Chromatography-Mass Spectrometry KW - Calibration KW - Dronabinol -- analysis KW - Sweat -- chemistry KW - Substance Abuse Detection -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67002147?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+chemistry&rft.atitle=Validated+gas+chromatographic-negative+ion+chemical+ionization+mass+spectrometric+method+for+delta%289%29-tetrahydrocannabinol+in+sweat+patches.&rft.au=Saito%2C+Takeshi%3BWtsadik%2C+Abraham%3BScheidweiler%2C+Karl+B%3BFortner%2C+Neil%3BTakeichi%2C+Sanae%3BHuestis%2C+Marilyn+A&rft.aulast=Saito&rft.aufirst=Takeshi&rft.date=2004-11-01&rft.volume=50&rft.issue=11&rft.spage=2083&rft.isbn=&rft.btitle=&rft.title=Clinical+chemistry&rft.issn=00099147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-02 N1 - Date created - 2004-10-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Chem. 2004 Nov;50(11):1961-2 [15502075] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions. AN - 66995351; 15495253 AB - The association between anabolic androgenic steroids and liver tumors was first noted in patients with Fanconi's anemia (FA). The hypotheses which led to this review were as follows: (1) androgen-treated individuals who do not have FA are also at risk of liver tumors; (2) parenteral as well as oral androgens may be responsible for liver tumors; (3) FA patients develop liver tumors after smaller and briefer androgen exposure than non-FA individuals; (4) the risk of hepatic neoplasms may depend on the specific androgen. Medline and Web of Science were searched for all cases of liver tumors associated with androgens. Information from individual cases was entered into a spreadsheet and descriptive statistical analyses were performed. Thirty-six FA cases and 97 non-FA cases with both nonhematologic disorders and acquired aplastic anemia (non-FA AA) were identified. The most common androgens were oxymetholone, methyltestosterone, and danazol. Hepatocellular carcinomas (HCC) were more often associated with oxymetholone and methyltestosterone, while adenomas were associated with danazol. Tumors were reported in six patients who received only parenteral and not oral androgens. FA patients were younger than non-FA patients when androgen use was initiated, and the FA patients developed tumors at younger ages. Non-AA patients were treated with androgens for longer periods of time, compared with FA and non-FA AA patients. All patients on anabolic androgenic steroids are at risk of liver tumors, regardless of underlying diagnosis. The magnitude of the risk cannot be determined from currently available data, because the number of patients receiving androgens is unknown. JF - American journal of hematology AU - Velazquez, Isela AU - Alter, Blanche P AD - Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland 20892, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 257 EP - 267 VL - 77 IS - 3 SN - 0361-8609, 0361-8609 KW - Anabolic Agents KW - 0 KW - Androgens KW - Estrogen Antagonists KW - Oxymetholone KW - L76T0ZCA8K KW - Danazol KW - N29QWW3BUO KW - Methyltestosterone KW - V9EFU16ZIF KW - Index Medicus KW - Anemia, Aplastic -- complications KW - Humans KW - Neoplasms, Hormone-Dependent -- pathology KW - Aged KW - Methyltestosterone -- adverse effects KW - Neoplasms, Hormone-Dependent -- chemically induced KW - Danazol -- adverse effects KW - Anabolic Agents -- adverse effects KW - Risk Factors KW - Anemia, Aplastic -- drug therapy KW - Estrogen Antagonists -- adverse effects KW - Adult KW - Middle Aged KW - Oxymetholone -- adverse effects KW - Female KW - Male KW - Liver Neoplasms -- pathology KW - Fanconi Anemia -- complications KW - Fanconi Anemia -- drug therapy KW - Androgens -- adverse effects KW - Liver Neoplasms -- chemically induced KW - Carcinoma, Hepatocellular -- pathology KW - Adenoma, Liver Cell -- pathology KW - Adenoma, Liver Cell -- chemically induced KW - Carcinoma, Hepatocellular -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66995351?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+hematology&rft.atitle=Androgens+and+liver+tumors%3A+Fanconi%27s+anemia+and+non-Fanconi%27s+conditions.&rft.au=Velazquez%2C+Isela%3BAlter%2C+Blanche+P&rft.aulast=Velazquez&rft.aufirst=Isela&rft.date=2004-11-01&rft.volume=77&rft.issue=3&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hematology&rft.issn=03618609&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-03 N1 - Date created - 2004-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intact signaling by transforming growth factor beta is not required for termination of liver regeneration in mice. AN - 66994728; 15389868 AB - Transforming growth factor beta (TGF-beta) is a potent inhibitor of hepatocyte proliferation in vitro and is suggested to be a key negative regulator of liver growth. To directly address the role of TGF-beta signaling in liver regeneration in vivo, the TGF-beta type II receptor gene (Tgfbr2) was selectively deleted in hepatocytes by crossing "floxed" Tgfbr2 conditional knockout mice with transgenic mice expressing Cre under control of the albumin promoter. Hepatocytes isolated from liver-specific Tgfbr2 knockout (R2LivKO) mice were refractory to the growth inhibitory effects of TGF-beta1. The peak of DNA synthesis after 70% partial hepatectomy occurred earlier (36 vs. 48 hours) and was 1.7-fold higher in R2LivKO mice compared with controls. Accelerated S-phase entry by proliferating R2LivKO hepatocytes coincided with the hyperphosphorylation of Rb protein and the early upregulation of cyclin D1 and cyclin E. However, by 120 hours after partial hepatectomy, hepatocyte proliferation was back to baseline in both control and R2LivKO liver. Regenerating R2LivKO liver showed evidence of increased signaling by activin A and persistent activity of the Smad pathway. Blockage of activin A signaling by the specific inhibitor follistatin resulted in increased hepatocyte proliferation at 120 hours, particularly in R2LivKO livers. In conclusion, TGF-beta regulates G(1) to S phase transition of hepatocytes, but intact signaling by TGF-beta is not required for termination of liver regeneration. Increased signaling by activin A may compensate to regulate liver regeneration when signaling through the TGF-beta pathway is abolished, and may be a principal factor in the termination of liver regeneration. JF - Hepatology (Baltimore, Md.) AU - Oe, Shoshiro AU - Lemmer, Eric R AU - Conner, Elizabeth A AU - Factor, Valentina M AU - Levéen, Per AU - Larsson, Jonas AU - Karlsson, Stefan AU - Thorgeirsson, Snorri S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4262, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 1098 EP - 1105 VL - 40 IS - 5 SN - 0270-9139, 0270-9139 KW - DNA-Binding Proteins KW - 0 KW - Follistatin KW - Receptors, Transforming Growth Factor beta KW - Smad Proteins KW - Tgfb1 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Transforming Growth Factor beta1 KW - activin A KW - Activins KW - 104625-48-1 KW - DNA KW - 9007-49-2 KW - Inhibin-beta Subunits KW - 93443-12-0 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Animals KW - Activins -- physiology KW - Cell Division -- drug effects KW - Cell Division -- physiology KW - Inhibin-beta Subunits -- physiology KW - Mice KW - DNA -- biosynthesis KW - Receptors, Transforming Growth Factor beta -- deficiency KW - Mice, Knockout KW - Activins -- antagonists & inhibitors KW - Follistatin -- pharmacology KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology KW - Hepatocytes -- cytology KW - Inhibin-beta Subunits -- antagonists & inhibitors KW - Transforming Growth Factor beta -- pharmacology KW - Signal Transduction -- physiology KW - Transforming Growth Factor beta -- physiology KW - Signal Transduction -- drug effects KW - Liver Regeneration -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66994728?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Intact+signaling+by+transforming+growth+factor+beta+is+not+required+for+termination+of+liver+regeneration+in+mice.&rft.au=Oe%2C+Shoshiro%3BLemmer%2C+Eric+R%3BConner%2C+Elizabeth+A%3BFactor%2C+Valentina+M%3BLev%C3%A9en%2C+Per%3BLarsson%2C+Jonas%3BKarlsson%2C+Stefan%3BThorgeirsson%2C+Snorri+S&rft.aulast=Oe&rft.aufirst=Shoshiro&rft.date=2004-11-01&rft.volume=40&rft.issue=5&rft.spage=1098&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 - 2004-11-19 N1 - Date created - 2004-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A model of inverse agonist action at thyrotropin-releasing hormone receptor type 1: role of a conserved tryptophan in helix 6. AN - 66993850; 15306657 AB - A binding pocket for thyrotropin-releasing hormone (TRH) within the transmembrane helices of the TRH receptor type 1 (TRH-R1) has been identified based on experimental evidence and computer simulations. To determine the binding site for a competitive inverse agonist, midazolam, three of the four residues that directly contact TRH and other residues that restrain TRH-R1 in an inactive conformation were screened by mutagenesis and binding assays. We found that two residues that directly contact TRH, Asn-110 in transmembrane helix 3 (3.37) and Arg-306 in transmembrane helix 7 (7.39), were important for midazolam binding but another, Tyr-282 in transmembrane helix 6 (6.51), was not. A highly conserved residue, Trp-279 in transmembrane helix 6 (6.48), which was reported to be critical in stabilizing TRH-R1 in an inactive state but not for TRH binding, was critical for midazolam binding. We used our previous model of the unoccupied TRH-R1 to generate a model of the TRH-R1/midazolam complex. The experimental results and the molecular model of the complex suggest that midazolam binds to TRH-R1 within a transmembrane helical pocket that partially overlaps the TRH binding pocket. This result is consistent with the competitive antagonism of midazolam binding. We suggest that the mechanism of inverse agonism effected by midazolam involves its direct interaction with Trp-279, which contributes to the stabilization of the inactive conformation of TRH-R1. JF - Molecular pharmacology AU - Lu, Xinping AU - Huang, Wei AU - Worthington, Sharon AU - Drabik, Piotr AU - Osman, Roman AU - Gershengorn, Marvin C AD - Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-1818, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 1192 EP - 1200 VL - 66 IS - 5 SN - 0026-895X, 0026-895X KW - Receptors, Thyrotropin-Releasing Hormone KW - 0 KW - Benzodiazepines KW - 12794-10-4 KW - Thyrotropin-Releasing Hormone KW - 5Y5F15120W KW - Tryptophan KW - 8DUH1N11BX KW - Midazolam KW - R60L0SM5BC KW - Index Medicus KW - Protein Structure, Secondary KW - Transfection KW - Models, Molecular KW - Cells, Cultured KW - Humans KW - Thyrotropin-Releasing Hormone -- metabolism KW - Signal Transduction -- drug effects KW - Benzodiazepines -- pharmacology KW - Receptors, Thyrotropin-Releasing Hormone -- chemistry KW - Receptors, Thyrotropin-Releasing Hormone -- drug effects KW - Tryptophan -- metabolism KW - Midazolam -- pharmacology KW - Receptors, Thyrotropin-Releasing Hormone -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66993850?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+model+of+inverse+agonist+action+at+thyrotropin-releasing+hormone+receptor+type+1%3A+role+of+a+conserved+tryptophan+in+helix+6.&rft.au=Lu%2C+Xinping%3BHuang%2C+Wei%3BWorthington%2C+Sharon%3BDrabik%2C+Piotr%3BOsman%2C+Roman%3BGershengorn%2C+Marvin+C&rft.aulast=Lu&rft.aufirst=Xinping&rft.date=2004-11-01&rft.volume=66&rft.issue=5&rft.spage=1192&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 - 2004-12-06 N1 - Date created - 2004-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Racial difference in lung function in African-American and White children: effect of anthropometric, socioeconomic, nutritional, and environmental factors. AN - 66992904; 15496542 AB - African-American children have lower lung volumes than White children. However, the contributions of anthropometric, socioeconomic, nutritional, and environmental factors to this difference are unknown. From participants in the Third National Health and Nutrition Examination Survey (1988-1994), the authors selected 1,462 healthy nonsmoking children (623 White and 839 African-American) aged 8-17 years. The African-American children were taller and heavier but had lower lung function. African Americans were poorer and had lower levels of the antioxidant vitamins A and C and alpha-carotene. The authors performed regression analyses using data on anthropometric, socioeconomic, and nutritional factors and smoke exposure. Adjustment for sitting height explained 42-53% of the racial difference. Socioeconomic factors and antioxidant vitamin levels accounted for an additional 7-10%. Overall, the authors could account for only 50-63% of the racial difference. Exposure to tobacco in the home was weakly associated with forced expiratory volume in 1 second in girls, accounting for 1% of the difference. In children aged 8-12 years (n = 752), birth weight explained 3-5% of the racial difference, whereas in-utero exposure to maternal smoking had no significant effect. The authors conclude that in healthy children, the major explanatory variable for the racial difference in lung function is body habitus; socioeconomic, nutritional, and environmental confounders play a smaller role. JF - American journal of epidemiology AU - Harik-Khan, Raida I AU - Muller, Denis C AU - Wise, Robert A AD - Clinical Research Branch, National Institute on Aging, Baltimore, MD, USA. Y1 - 2004/11/01/ PY - 2004 DA - 2004 Nov 01 SP - 893 EP - 900 VL - 160 IS - 9 SN - 0002-9262, 0002-9262 KW - Antioxidants KW - 0 KW - Tobacco Smoke Pollution KW - Index Medicus KW - Nutritional Status KW - Regression Analysis KW - Reference Values KW - Body Height KW - Child Nutritional Physiological Phenomena KW - Nutrition Assessment KW - Humans KW - Nutrition Surveys KW - Child KW - Multivariate Analysis KW - Socioeconomic Factors KW - Anthropometry KW - Body Weight KW - Cross-Sectional Studies KW - Antioxidants -- metabolism KW - Confounding Factors (Epidemiology) KW - Tobacco Smoke Pollution -- adverse effects KW - Surveys and Questionnaires KW - Adolescent KW - Environmental Exposure -- adverse effects KW - Poverty -- statistics & numerical data KW - Vital Capacity KW - African Americans -- statistics & numerical data KW - European Continental Ancestry Group -- statistics & numerical data KW - African Americans -- genetics KW - Forced Expiratory Volume KW - European Continental Ancestry Group -- ethnology KW - African Americans -- ethnology KW - European Continental Ancestry Group -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66992904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Racial+difference+in+lung+function+in+African-American+and+White+children%3A+effect+of+anthropometric%2C+socioeconomic%2C+nutritional%2C+and+environmental+factors.&rft.au=Harik-Khan%2C+Raida+I%3BMuller%2C+Denis+C%3BWise%2C+Robert+A&rft.aulast=Harik-Khan&rft.aufirst=Raida&rft.date=2004-11-01&rft.volume=160&rft.issue=9&rft.spage=893&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 - 2004-11-16 N1 - Date created - 2004-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Developing effective evidence-based interventions for adolescents with alcohol use disorders. AN - 66983495; 15488101 JF - Addiction (Abingdon, England) AU - Lowman, Cherry AD - Division of Treatment and Recovery Research, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2051, Bethesda, MD 20892-9304, USA. clowman@willco.niaaa.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 1 EP - 4 VL - 99 Suppl 2 SN - 0965-2140, 0965-2140 KW - Index Medicus KW - Humans KW - Psychology, Adolescent KW - Research KW - Adolescent KW - Evidence-Based Medicine KW - Alcoholism -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66983495?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Developing+effective+evidence-based+interventions+for+adolescents+with+alcohol+use+disorders.&rft.au=Lowman%2C+Cherry&rft.aulast=Lowman&rft.aufirst=Cherry&rft.date=2004-11-01&rft.volume=99+Suppl+2&rft.issue=&rft.spage=1&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 - 2005-05-03 N1 - Date created - 2004-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Uterus hyperplasia and increased carcinogen-induced tumorigenesis in mice carrying a targeted mutation of the Chk2 phosphorylation site in Brca1. AN - 66979990; 15485917 AB - The tumor suppressor BRCA1 contains multiple functional domains that interact with many proteins. After DNA damage, BRCA1 is phosphorylated by CHK2 at serine 988, followed by a change in its intracellular location. To study the functions of CHK2-dependent phosphorylation of BRCA1, we generated a mouse model carrying the mutation S971A (S971 in mouse Brca1 corresponds to S988 in human BRCA1) by gene targeting. Brca1(S971A/S971A) mice were born at the expected ratio without a developmental defect, unlike previously reported Brca1 mutant mice. However, Brca1(S971A/S971A) mice suffered a moderately increased risk of spontaneous tumor formation, with a majority of females developing uterus hyperplasia and ovarian abnormalities by 2 years of age. After treatment with DNA-damaging agents, Brca1(S971A/S971A) mice exhibited several abnormalities, including increased body weight, abnormal hair growth pattern, lymphoma, mammary tumors, and endometrial tumors. In addition, the onset of tumor formation became accelerated, and 80% of the mutant mice had developed tumors by 1 year of age. We demonstrated that the Brca1(S971A/S971A) cells displayed reduced ability to activate the G(2)/M cell cycle checkpoint upon gamma-irradiation and to stabilize p53 following N-methyl-N'-nitro-N-nitrosoguanidine treatment. These observations suggest that Chk2 phosphorylation of S971 is involved in Brca1 function in modulating the DNA damage response and repressing tumor formation. JF - Molecular and cellular biology AU - Kim, Sang Soo AU - Cao, Liu AU - Li, Cuiling AU - Xu, Xiaoling AU - Huber, L Julie AU - Chodosh, Lewis A AU - Deng, Chu-Xia AD - Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, 10/9N105, 10 Center Dr., Bethesda, MD 20892, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 9498 EP - 9507 VL - 24 IS - 21 SN - 0270-7306, 0270-7306 KW - BRCA1 Protein KW - 0 KW - Carcinogens KW - Methylnitronitrosoguanidine KW - 12H3O2UGSF KW - Serine KW - 452VLY9402 KW - Checkpoint Kinase 2 KW - EC 2.7.1.11 KW - CHEK2 protein, human KW - EC 2.7.11.1 KW - Chek2 protein, mouse KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Animals KW - Mammary Glands, Animal -- drug effects KW - Gamma Rays KW - Mammary Glands, Animal -- radiation effects KW - DNA Damage KW - Aging KW - Mice KW - Serine -- metabolism KW - Serine -- genetics KW - Phenotype KW - Survival Rate KW - Phosphorylation KW - Mammary Glands, Animal -- pathology KW - Methylnitronitrosoguanidine -- pharmacology KW - Mutation -- genetics KW - Cell Cycle -- radiation effects KW - Female KW - Hyperplasia -- pathology KW - Protein-Serine-Threonine Kinases -- metabolism KW - Cell Transformation, Neoplastic -- pathology KW - Mutagenesis, Site-Directed -- genetics KW - BRCA1 Protein -- genetics KW - Cell Transformation, Neoplastic -- metabolism KW - Carcinogens -- toxicity KW - Hyperplasia -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - BRCA1 Protein -- chemistry KW - Uterus -- drug effects KW - Uterus -- metabolism KW - Hyperplasia -- chemically induced KW - Cell Transformation, Neoplastic -- radiation effects KW - Hyperplasia -- genetics KW - BRCA1 Protein -- metabolism KW - Cell Transformation, Neoplastic -- chemically induced KW - Uterus -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66979990?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Uterus+hyperplasia+and+increased+carcinogen-induced+tumorigenesis+in+mice+carrying+a+targeted+mutation+of+the+Chk2+phosphorylation+site+in+Brca1.&rft.au=Kim%2C+Sang+Soo%3BCao%2C+Liu%3BLi%2C+Cuiling%3BXu%2C+Xiaoling%3BHuber%2C+L+Julie%3BChodosh%2C+Lewis+A%3BDeng%2C+Chu-Xia&rft.aulast=Kim&rft.aufirst=Sang&rft.date=2004-11-01&rft.volume=24&rft.issue=21&rft.spage=9498&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 - 2004-12-03 N1 - Date created - 2004-10-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1999 Nov 5;286(5442):1162-6 [10550055] J Clin Invest. 1999 Dec;104(11):1517-25 [10587515] Science. 1999 Dec 24;286(5449):2528-31 [10617473] Science. 2000 Mar 10;287(5459):1824-7 [10710310] Nature. 2000 Mar 9;404(6774):201-4 [10724175] Nat Genet. 2000 May;25(1):115-9 [10802669] Bioessays. 2000 Aug;22(8):728-37 [10918303] Curr Biol. 2000 Jul 27-Aug 10;10(15):886-95 [10959836] Cancer Res. 2000 Sep 1;60(17):4689-92 [10987268] Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10389-94 [10973490] Nature. 2000 Nov 23;408(6811):433-9 [11100718] Oncogene. 2000 Dec 11;19(53):6159-75 [11156530] Leuk Res. 2001 Apr;25(4):333-8 [11248330] Gynecol Oncol. 2001 Mar;80(3):395-8 [11263938] Nature. 2001 Apr 12;410(6830):842-7 [11298456] Mol Cell Biol. 2001 May;21(10):3445-50 [11313470] Genes Dev. 2001 May 15;15(10):1188-93 [11358863] Mol Cell Biol. 2001 Jun;21(12):4005-15 [11359908] Nat Genet. 2001 Jul;28(3):266-71 [11431698] Br J Cancer. 2001 Jul 20;85(2):209-12 [11461078] Breast Cancer Res. 2003;5(3):123-5 [12793891] Mol Cell Biol. 2004 Jan;24(2):708-18 [14701743] Hum Mol Genet. 1994 Feb;3(2):253-6 [8004091] Science. 1994 Oct 7;266(5182):66-71 [7545954] Genes Dev. 1994 Dec 15;8(24):3045-57 [8001823] Cell. 1995 Aug 25;82(4):675-84 [7664346] Genes Dev. 1995 Nov 1;9(21):2712-22 [7590247] Cell. 1996 Mar 22;84(6):911-21 [8601314] Cell Growth Differ. 1996 Jun;7(6):711-5 [8780884] Cancer Res. 1997 Mar 15;57(6):1171-9 [9067289] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7138-43 [9207057] Curr Opin Oncol. 1997 Nov;9(6):505-11 [9370070] Medicine (Baltimore). 1998 May;77(3):208-26 [9653432] Eur J Cancer. 1998 Oct;34(11):1770-6 [9893667] EMBO J. 1999 Mar 1;18(5):1280-91 [10064594] Nat Genet. 1999 Apr;21(4):359-60 [10192382] Mol Cell. 1999 Mar;3(3):389-95 [10198641] Nat Genet. 1999 May;22(1):37-43 [10319859] Oncogene. 2001 Nov 8;20(51):7514-23 [11709723] Genes Chromosomes Cancer. 2002 Jan;33(1):17-21 [11746983] Cell. 2002 Jan 25;108(2):171-82 [11832208] Oncogene. 2002 Feb 21;21(9):1316-24 [11857075] Br J Cancer. 2002 Mar 4;86(5):756-60 [11875739] Environ Mol Mutagen. 2002;39(2-3):171-7 [11921186] Blood. 2002 Apr 15;99(8):3075-7 [11949635] Nat Genet. 2002 May;31(1):55-9 [11967536] J Biol Chem. 2002 Aug 9;277(32):28641-7 [12039951] Cancer Res. 2002 Aug 15;62(16):4588-91 [12183412] Oncogene. 2002 Sep 9;21(40):6222-7 [12214252] EMBO J. 2002 Oct 1;21(19):5195-205 [12356735] Cell. 2002 Oct 4;111(1):41-50 [12372299] J Biol Chem. 2003 Jan 17;278(3):2015-20 [12427729] Genes Dev. 2003 Jan 15;17(2):201-13 [12533509] Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R113-23 [12668603] J Biol Chem. 2003 Apr 18;278(16):13599-602 [12611903] Am J Hum Genet. 2003 May;72(5):1308-14 [12690581] Cancer Cell. 2003 May;3(5):421-9 [12781359] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of the proteins required for biosynthesis of diphthamide, the target of bacterial ADP-ribosylating toxins on translation elongation factor 2. AN - 66979076; 15485916 AB - Diphthamide, a posttranslational modification of translation elongation factor 2 that is conserved in all eukaryotes and archaebacteria and is the target of diphtheria toxin, is formed in yeast by the actions of five proteins, Dph1 to -5, and a still unidentified amidating enzyme. Dph2 and Dph5 were previously identified. Here, we report the identification of the remaining three yeast proteins (Dph1, -3, and -4) and show that all five Dph proteins have either functional (Dph1, -2, -3, and -5) or sequence (Dph4) homologs in mammals. We propose a unified nomenclature for these proteins (e.g., HsDph1 to -5 for the human proteins) and their genes based on the yeast nomenclature. We show that Dph1 and Dph2 are homologous in sequence but functionally independent. The human tumor suppressor gene OVCA1, previously identified as homologous to yeast DPH2, is shown to actually be HsDPH1. We show that HsDPH3 is the previously described human diphtheria toxin and Pseudomonas exotoxin A sensitivity required gene 1 and that DPH4 encodes a CSL zinc finger-containing DnaJ-like protein. Other features of these genes are also discussed. The physiological function of diphthamide and the basis of its ubiquity remain a mystery, but evidence is presented that Dph1 to -3 function in vivo as a protein complex in multiple cellular processes. JF - Molecular and cellular biology AU - Liu, Shihui AU - Milne, G Todd AU - Kuremsky, Jeffrey G AU - Fink, Gerald R AU - Leppla, Stephen H AD - Microbial Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 9487 EP - 9497 VL - 24 IS - 21 SN - 0270-7306, 0270-7306 KW - DPH1 protein, human KW - 0 KW - Diphtheria Toxin KW - Dph1 protein, S cerevisiae KW - Iron-Sulfur Proteins KW - Minor Histocompatibility Antigens KW - Peptide Elongation Factor 2 KW - Proteins KW - Saccharomyces cerevisiae Proteins KW - Tumor Suppressor Proteins KW - Histidine KW - 4QD397987E KW - Adenosine Diphosphate KW - 61D2G4IYVH KW - diphthamide KW - 75645-22-6 KW - Index Medicus KW - Animals KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Drug Resistance -- drug effects KW - Saccharomyces cerevisiae Proteins -- genetics KW - Humans KW - Tumor Suppressor Proteins -- genetics KW - Iron-Sulfur Proteins -- genetics KW - Iron-Sulfur Proteins -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - Saccharomyces cerevisiae -- metabolism KW - Sequence Alignment KW - Tumor Suppressor Proteins -- metabolism KW - Genetic Complementation Test KW - Molecular Sequence Data KW - CHO Cells KW - Adenosine Diphosphate -- metabolism KW - Molecular Structure KW - Phylogeny KW - Amino Acid Sequence KW - Mice KW - Protein Binding KW - Cloning, Molecular KW - Genes, Fungal -- genetics KW - Mutation -- genetics KW - Cricetinae KW - Histidine -- chemistry KW - Peptide Elongation Factor 2 -- metabolism KW - Histidine -- deficiency KW - Histidine -- biosynthesis KW - Diphtheria Toxin -- pharmacology KW - Histidine -- analogs & derivatives KW - Proteins -- metabolism KW - Proteins -- genetics KW - Histidine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66979076?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Identification+of+the+proteins+required+for+biosynthesis+of+diphthamide%2C+the+target+of+bacterial+ADP-ribosylating+toxins+on+translation+elongation+factor+2.&rft.au=Liu%2C+Shihui%3BMilne%2C+G+Todd%3BKuremsky%2C+Jeffrey+G%3BFink%2C+Gerald+R%3BLeppla%2C+Stephen+H&rft.aulast=Liu&rft.aufirst=Shihui&rft.date=2004-11-01&rft.volume=24&rft.issue=21&rft.spage=9487&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 - 2004-12-03 N1 - Date created - 2004-10-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Microbiol. 2003 Sep;49(5):1297-307 [12940988] EMBO J. 2003 May 1;22(9):1953-8 [12727863] Nature. 2003 Oct 16;425(6959):686-91 [14562095] Genes Dev. 2004 Feb 1;18(3):320-32 [14744934] Somatic Cell Genet. 1979 Jul;5(4):453-68 [494060] Proc Natl Acad Sci U S A. 1980 Feb;77(2):1010-4 [6928655] J Biol Chem. 1980 Nov 25;255(22):10710-6 [7430147] J Biol Chem. 1983 Apr 25;258(8):4754-8 [6339504] Mol Cell Biol. 1984 Apr;4(4):642-50 [6717439] Proc Natl Acad Sci U S A. 1984 May;81(9):2703-7 [6326138] Mol Cell Biol. 1985 Dec;5(12):3357-60 [3915773] Gene. 1987;60(2-3):237-43 [3327750] J Biol Chem. 1988 Aug 25;263(24):11692-6 [3042777] Methods Enzymol. 1988;165:68-76 [3148099] Mol Cell Biol. 1992 Sep;12(9):4026-37 [1508200] Nucleic Acids Res. 1993 Jul 11;21(14):3329-30 [8341614] Gene. 1993 Sep 30;132(1):149-54 [8406038] J Biol Chem. 1994 May 6;269(18):13497-501 [8175783] Genes Dev. 1994 May 1;8(9):1087-105 [7926789] Cancer Res. 1996 Feb 1;56(3):606-11 [8564979] Cancer Lett. 1996 Apr 19;102(1-2):85-90 [8603384] Cancer Res. 1996 May 1;56(9):1997-2002 [8616839] J Mol Biol. 1996 Jul 12;260(2):236-50 [8764403] Physiol Rev. 1999 Apr;79(2):425-49 [10221986] Cancer Res. 1999 Oct 1;59(19):4973-83 [10519411] Gene. 2001 Aug 8;273(2):267-74 [11595173] J Mol Microbiol Biotechnol. 2002 May;4(3):243-8 [11931554] Mol Microbiol. 2002 May;44(3):865-75 [11994165] Nucleic Acids Res. 2003 Jan 1;31(1):383-7 [12520028] Nat Struct Biol. 2003 May;10(5):379-85 [12692531] Mol Cell. 2003 Sep;12(3):603-13 [14527407] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interactions of eukaryotic translation initiation factor 3 (eIF3) subunit NIP1/c with eIF1 and eIF5 promote preinitiation complex assembly and regulate start codon selection. AN - 66976516; 15485912 AB - The N-terminal domain (NTD) of NIP1/eIF3c interacts directly with eIF1 and eIF5 and indirectly through eIF5 with the eIF2-GTP-Met-tRNA(i)(Met) ternary complex (TC) to form the multifactor complex (MFC). We investigated the physiological importance of these interactions by mutating 16 segments spanning the NIP1-NTD. Mutations in multiple segments reduced the binding of eIF1 or eIF5 to the NIP1-NTD. Mutating a C-terminal segment of the NIP1-NTD increased utilization of UUG start codons (Sui(-) phenotype) and was lethal in cells expressing eIF5-G31R that is hyperactive in stimulating GTP hydrolysis by the TC at AUG codons. Both effects of this NIP1 mutation were suppressed by eIF1 overexpression, as was the Sui(-) phenotype conferred by eIF5-G31R. Mutations in two N-terminal segments of the NIP1-NTD suppressed the Sui(-) phenotypes produced by the eIF1-D83G and eIF5-G31R mutations. From these and other findings, we propose that the NIP1-NTD coordinates an interaction between eIF1 and eIF5 that inhibits GTP hydrolysis at non-AUG codons. Two NIP1-NTD mutations were found to derepress GCN4 translation in a manner suppressed by overexpressing the TC, indicating that MFC formation stimulates TC recruitment to 40S ribosomes. Thus, the NIP1-NTD is required for efficient assembly of preinitiation complexes and also regulates the selection of AUG start codons in vivo. JF - Molecular and cellular biology AU - Valásek, Leos AU - Nielsen, Klaus H AU - Zhang, Fan AU - Fekete, Christie A AU - Hinnebusch, Alan G AD - Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. valasekl@biomed.cas.cz Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 9437 EP - 9455 VL - 24 IS - 21 SN - 0270-7306, 0270-7306 KW - Codon, Initiator KW - 0 KW - DNA-Binding Proteins KW - Eukaryotic Initiation Factor-1 KW - Eukaryotic Initiation Factor-3 KW - Eukaryotic Initiation Factor-5 KW - NIP1 protein, S cerevisiae KW - Nuclear Proteins KW - Prokaryotic Initiation Factor-3 KW - Protein Subunits KW - RNA, Transfer, Met KW - Saccharomyces cerevisiae Proteins KW - Guanosine Triphosphate KW - 86-01-1 KW - Protein Kinases KW - EC 2.7.- KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Gene Expression Regulation, Fungal KW - Ribosomes -- metabolism KW - Models, Molecular KW - Protein Kinases -- biosynthesis KW - DNA-Binding Proteins -- biosynthesis KW - DNA-Binding Proteins -- genetics KW - Amino Acid Sequence KW - Protein Subunits -- metabolism KW - Protein Binding KW - Protein Structure, Quaternary KW - Guanosine Triphosphate -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - Mutagenesis, Site-Directed KW - Phenotype KW - Saccharomyces cerevisiae -- metabolism KW - RNA, Transfer, Met -- metabolism KW - Alanine -- metabolism KW - Protein Kinases -- genetics KW - Molecular Sequence Data KW - Alanine -- genetics KW - Saccharomyces cerevisiae Proteins -- metabolism KW - Nuclear Proteins -- genetics KW - Codon, Initiator -- genetics KW - Saccharomyces cerevisiae Proteins -- genetics KW - Prokaryotic Initiation Factor-3 -- chemistry KW - Eukaryotic Initiation Factor-5 -- metabolism KW - Prokaryotic Initiation Factor-3 -- genetics KW - Eukaryotic Initiation Factor-1 -- metabolism KW - Protein Biosynthesis -- genetics KW - Prokaryotic Initiation Factor-3 -- metabolism KW - Saccharomyces cerevisiae Proteins -- biosynthesis KW - Nuclear Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66976516?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Interactions+of+eukaryotic+translation+initiation+factor+3+%28eIF3%29+subunit+NIP1%2Fc+with+eIF1+and+eIF5+promote+preinitiation+complex+assembly+and+regulate+start+codon+selection.&rft.au=Val%C3%A1sek%2C+Leos%3BNielsen%2C+Klaus+H%3BZhang%2C+Fan%3BFekete%2C+Christie+A%3BHinnebusch%2C+Alan+G&rft.aulast=Val%C3%A1sek&rft.aufirst=Leos&rft.date=2004-11-01&rft.volume=24&rft.issue=21&rft.spage=9437&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 - 2004-12-03 N1 - Date created - 2004-10-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genes Dev. 1997 Sep 15;11(18):2396-413 [9308967] EMBO J. 1999 May 4;18(9):2631-7 [10228174] Genes Dev. 2000 Oct 1;14(19):2534-46 [11018020] EMBO J. 2001 May 1;20(9):2326-37 [11331597] RNA. 2002 Mar;8(3):382-97 [12008673] EMBO J. 2002 Nov 1;21(21):5886-98 [12411506] Genes Dev. 2002 Nov 15;16(22):2906-22 [12435632] Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16689-94 [12471154] EMBO J. 2003 Jan 15;22(2):193-204 [12514125] J Biol Chem. 2003 Feb 21;278(8):6580-7 [12493757] Genes Dev. 2003 Mar 15;17(6):786-99 [12651896] J Mol Biol. 2003 Jul 25;330(5):917-24 [12860115] Mol Cell Biol. 2003 Aug;23(15):5431-45 [12861028] Genes Dev. 2003 Nov 15;17(22):2786-97 [14600024] EMBO J. 2004 Mar 10;23(5):1166-77 [14976554] Cell. 1986 Apr 25;45(2):201-7 [3516411] Proc Natl Acad Sci U S A. 1987 Jul;84(14):4767-71 [3474623] Mol Cell Biol. 1988 Jul;8(7):2964-75 [3043201] Gene. 1988 Dec 30;74(2):527-34 [3073106] Mol Cell Biol. 1991 May;11(5):2723-35 [2017175] Mol Cell Biol. 1992 Jan;12(1):248-60 [1729602] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10355-9 [1332047] J Biol Chem. 1995 Mar 3;270(9):4288-92 [7876188] Mol Cell Biol. 1998 Aug;18(8):4935-46 [9671501] Nature. 1998 Aug 27;394(6696):854-9 [9732867] EMBO J. 1999 Mar 15;18(6):1673-88 [10075937] Nature. 2000 Jan 20;403(6767):332-5 [10659855] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)pyridine and its analogues as PET radioligands for imaging nicotinic acetylcholine receptors. AN - 66975862; 15485491 AB - A novel series of compounds derived from the high-affinity nicotinic acetylcholine receptor (nAChR) ligand, 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-((1-methyl-2-(S)-pyrrolidinyl)methoxy)pyridine (Me-p-PVC), originally developed by Abbott Laboratories, was characterized in vitro in nAChR binding assays at 37 degrees C to show K(i) values in the range of 9-611 pm. Several compounds of this series were radiolabeled with (11)C and evaluated in vivo in mice and monkeys as potential candidates for PET imaging of nAChRs. [(11)C]Me-p-PVC (K(i) =56 pm at 37 degrees C; logD = 1.6) was identified as a radioligand suitable for the in vivo imaging of the alpha 4 beta 2* nAChR subtype. Compared with 2-[(18)F]FA, a PET radioligand that has been successfully used in humans and is characterized by a slow kinetic of brain distribution, [(11)C]Me-p-PVC is more lipophilic. As a result, [(11)C]Me-p-PVC accumulated in the brain more rapidly than 2-[(18)F]FA. Pharmacological evaluation of Me-p-PVC in mice demonstrated that the toxicity of this compound was comparable with or lower than that of 2-FA. Taken together, these results suggest that [(11)C]Me-p-PVC is a promising PET radioligand for studying nAChR occupancy by endogenous and exogenous ligands in the brain in vivo. JF - Journal of neurochemistry AU - Brown, LaVerne AU - Chefer, Svetlana AU - Pavlova, Olga AU - Vaupel, D Bruce AU - Koren, Andrei O AU - Kimes, Alane S AU - Horti, Andrew G AU - Mukhin, Alexey G AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 600 EP - 612 VL - 91 IS - 3 SN - 0022-3042, 0022-3042 KW - 2-fluoro-3-(2-azetidinylmethoxy)pyridine KW - 0 KW - 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-methyl-2-pyrrolidinylmethoxy)pyridine KW - Azetidines KW - Carbon Radioisotopes KW - Pyridines KW - Pyrrolidines KW - Receptors, Nicotinic KW - nicotinic receptor alpha4beta2 KW - Index Medicus KW - Rats KW - Animals KW - Azetidines -- pharmacokinetics KW - Dose-Response Relationship, Drug KW - Mice KW - Macaca mulatta KW - Drug Evaluation, Preclinical KW - Male KW - Carbon Radioisotopes -- chemistry KW - Pyridines -- chemistry KW - Receptors, Nicotinic -- metabolism KW - Positron-Emission Tomography -- methods KW - Pyrrolidines -- chemistry KW - Pyridines -- pharmacokinetics KW - Pyrrolidines -- pharmacokinetics KW - Receptors, Nicotinic -- drug effects KW - Pyrrolidines -- pharmacology KW - Binding, Competitive -- drug effects KW - Brain -- metabolism KW - Pyridines -- pharmacology KW - Brain -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66975862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Evaluation+of+5-%282-%284-pyridinyl%29vinyl%29-6-chloro-3-%281-methyl-2-%28S%29-pyrrolidinylmethoxy%29pyridine+and+its+analogues+as+PET+radioligands+for+imaging+nicotinic+acetylcholine+receptors.&rft.au=Brown%2C+LaVerne%3BChefer%2C+Svetlana%3BPavlova%2C+Olga%3BVaupel%2C+D+Bruce%3BKoren%2C+Andrei+O%3BKimes%2C+Alane+S%3BHorti%2C+Andrew+G%3BMukhin%2C+Alexey+G&rft.aulast=Brown&rft.aufirst=LaVerne&rft.date=2004-11-01&rft.volume=91&rft.issue=3&rft.spage=600&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 - 2005-03-24 N1 - Date created - 2004-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exendin-4 pharmacodynamics: insights from the hyperglycemic clamp technique. AN - 66975132; 15199095 AB - The purpose of this study is to ascertain the pharmacodynamic properties of exendin-4, a glucose-dependent insulinotropic agent, from plasma glucose and insulin concentration-time profiles following a 60-min intravenous infusion in healthy and type 2 diabetic subjects. Plasma glucose and insulin concentrations were obtained from a previous clinical study, whereby a hyperglycemic clamp was established and maintained in healthy (n = 7) and type 2 diabetic (n = 7) volunteers (plasma glucose raised 5.4 mM above fasting level). Exendin-4 was infused (0.15 pmol/kg/min) during the 2nd hour of a 5-h clamp. A physiological pharmacodynamic model was developed and fitted to individual glucose and insulin responses simultaneously. Because drug concentrations were unavailable, hypothetical pharmacokinetic driving functions were approximated during the modeling process and used to enhance a proportionality constant relating elevated glucose and the rate of second-phase insulin release. Exendin-4 infusions produced substantial insulin release in both subject populations that required higher glucose infusion rates to maintain stable hyperglycemia. Observed plasma glucose-insulin profiles were well characterized by the final pharmacodynamic model. Apparent exendin-4 elimination rate constants for healthy and diabetic subjects were similar (0.0386 +/- 0.0192 and 0.0460 +/- 0.0145 min(-1)). Capacity and sensitivity parameters of drug effect were 2-fold lower in diabetic subjects, but mean differences were not statistically significant. Simulations confirm that diabetic subjects exhibit a reduced capacity to enhance second-phase insulin release in response to exendin-4 compared with healthy subjects. Type 2 diabetic subjects demonstrate a significant response to exendin-4, but to a lesser extent than nondiabetic subjects, despite comparable measures of apparent drug exposure and efficacy. JF - The Journal of pharmacology and experimental therapeutics AU - Mager, Donald E AU - Abernethy, Darrell R AU - Egan, Josephine M AU - Elahi, Dariush AD - Gerontology Research Center, National Institute on Aging/NIH, 5600 Nathan Shock Dr., Baltimore, MD 21224-6825, USA. magerdo@grc.nia.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 830 EP - 835 VL - 311 IS - 2 SN - 0022-3565, 0022-3565 KW - Insulin KW - 0 KW - Peptides KW - Venoms KW - exenatide KW - 9P1872D4OL KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Humans KW - Models, Biological KW - Hyperglycemia -- metabolism KW - Glucose -- metabolism KW - Insulin -- metabolism KW - Venoms -- pharmacokinetics KW - Diabetes Mellitus, Type 2 -- metabolism KW - Peptides -- pharmacology KW - Homeostasis -- drug effects KW - Peptides -- pharmacokinetics KW - Venoms -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66975132?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Exendin-4+pharmacodynamics%3A+insights+from+the+hyperglycemic+clamp+technique.&rft.au=Mager%2C+Donald+E%3BAbernethy%2C+Darrell+R%3BEgan%2C+Josephine+M%3BElahi%2C+Dariush&rft.aulast=Mager&rft.aufirst=Donald&rft.date=2004-11-01&rft.volume=311&rft.issue=2&rft.spage=830&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 - 2005-01-25 N1 - Date created - 2004-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pyridoxine-induced toxicity in rats: a stereological quantification of the sensory neuropathy. AN - 66960326; 15473987 AB - Excess ingestion of pyridoxine (vitamin B6) causes a severe sensory neuropathy in humans. The mechanism of action has not been fully elucidated, and studies of pyridoxine neuropathy in experimental animals have yielded disparate results. Pyridoxine intoxication appears to produce a neuropathy characterized by necrosis of dorsal root ganglion (DRG) sensory neurons and degeneration of peripheral and central sensory projections, with large diameter neurons being particularly affected. The major determinants affecting the severity of the pyridoxine neuropathy appear to be duration and dose of pyridoxine administration, differential neuronal vulnerability, and species susceptibility. The present study used design-based stereological techniques in conjunction with electrophysiological measures to quantify the morphological and physiological changes that occur in the DRG and the distal myelinated axons of the sciatic nerve following pyridoxine intoxication. This combined stereological and electrophysiological method demonstrates a general approach that could be used for assessing the correlation between pathophysiological and functional parameters in animal models of toxic neuropathy. JF - Experimental neurology AU - Perry, Tracy Ann AU - Weerasuriya, Ananda AU - Mouton, Peter R AU - Holloway, Harold W AU - Greig, Nigel H AD - Section of Drug Design and Development, Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. tracyann.perry@nia.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 133 EP - 144 VL - 190 IS - 1 SN - 0014-4886, 0014-4886 KW - Pyridoxine KW - KV2JZ1BI6Z KW - Index Medicus KW - Animals KW - Neural Conduction -- drug effects KW - Cell Count -- statistics & numerical data KW - Disease Progression KW - Disease Models, Animal KW - Electrophysiology KW - Sciatic Nerve -- drug effects KW - Cell Size -- drug effects KW - H-Reflex -- drug effects KW - Rats KW - Motor Neurons -- pathology KW - Rats, Sprague-Dawley KW - Psychomotor Performance -- drug effects KW - Ganglia, Spinal -- pathology KW - Nerve Fibers, Myelinated -- pathology KW - Sciatic Nerve -- pathology KW - Nerve Fibers, Myelinated -- drug effects KW - Motor Neurons -- drug effects KW - Male KW - Sensation Disorders -- pathology KW - Neurodegenerative Diseases -- physiopathology KW - Neurodegenerative Diseases -- chemically induced KW - Sensation Disorders -- physiopathology KW - Sensation Disorders -- chemically induced KW - Pyridoxine -- toxicity KW - Neurodegenerative Diseases -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66960326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Pyridoxine-induced+toxicity+in+rats%3A+a+stereological+quantification+of+the+sensory+neuropathy.&rft.au=Perry%2C+Tracy+Ann%3BWeerasuriya%2C+Ananda%3BMouton%2C+Peter+R%3BHolloway%2C+Harold+W%3BGreig%2C+Nigel+H&rft.aulast=Perry&rft.aufirst=Tracy&rft.date=2004-11-01&rft.volume=190&rft.issue=1&rft.spage=133&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 - 2005-01-13 N1 - Date created - 2004-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IFN-gamma/STAT1 acts as a proinflammatory signal in T cell-mediated hepatitis via induction of multiple chemokines and adhesion molecules: a critical role of IRF-1. AN - 66951083; 15246962 AB - We have previously shown that IFN-gamma/STAT1 plays an essential role in concanavalin A (ConA)-induced T cell hepatitis via activation of apoptotic signaling pathways. Here we demonstrate that IFN-gamma/STAT1 also plays a crucial role in leukocyte infiltration into the liver in T cell hepatitis. After injection of ConA, leukocytes were significantly infiltrated into the liver, which was suppressed in IFN-gamma(-/-) and STAT1(-/-) mice. Disruption of the IFN regulatory factor-1 (IRF-1) gene, a downstream target of IFN-gamma/STAT1, abolished ConA-induced liver injury and suppressed leukocyte infiltration into the liver. Additionally, ConA injection induced expression of a wide variety of chemokines and adhesion molecules in the liver. Among them, expression of ICAM-1, VCAM-1, monokine induced by IFN-gamma (Mig), CC chemokine ligand-20, epithelial cell-derived neutrophil-activating peptide (ENA)-78, IFN-inducible T cell-alpha chemoattractant (I-TAC), and IFN-inducible protein-10 (IP-10) was markedly attenuated in IFN-gamma(-/-), STAT1(-/-), and IRF-1(-/-) mice. In primary mouse hepatocytes, Kupffer cells, and endothelial cells, in vitro treatment with IFN-gamma activated STAT1, STAT3, and IRF-1, and induced expression of VCAM-1, ICAM-1, Mig, ENA-78, I-TAC, and IP-10 mRNA. Induction of these chemokines and adhesion molecules was markedly diminished in STAT1(-/-) and IRF-1(-/-) hepatic cells compared with wild-type hepatic cells. These findings suggest that in addition to induction of apoptosis, previously well documented, IFN-gamma also stimulated hepatocytes, sinusoidal endothelial cells, and Kupffer cells partly via an STAT1/IRF-1-dependent mechanism to produce multiple chemokines and adhesive molecules responsible for promoting infiltration of leukocytes and, ultimately, resulting in hepatitis. JF - American journal of physiology. Gastrointestinal and liver physiology AU - Jaruga, Barbara AU - Hong, Feng AU - Kim, Won-Ho 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 - 2004/11// PY - 2004 DA - November 2004 SP - G1044 EP - G1052 VL - 287 IS - 5 SN - 0193-1857, 0193-1857 KW - Cell Adhesion Molecules KW - 0 KW - Chemokines KW - DNA-Binding Proteins KW - Inflammation Mediators KW - Interferon Regulatory Factor-1 KW - Irf1 protein, mouse KW - Phosphoproteins KW - STAT1 Transcription Factor KW - Stat1 protein, mouse KW - Trans-Activators KW - Concanavalin A KW - 11028-71-0 KW - Interferon-gamma KW - 82115-62-6 KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Liver -- immunology KW - Chemokines -- biosynthesis KW - Mice KW - Neutrophil Infiltration KW - Mice, Knockout KW - Liver -- drug effects KW - Eosinophils KW - Mice, Inbred C57BL KW - Kupffer Cells -- metabolism KW - Cell Adhesion Molecules -- biosynthesis KW - Male KW - Endothelial Cells -- metabolism KW - Hepatocytes -- metabolism KW - Trans-Activators -- metabolism KW - Hepatitis, Animal -- metabolism KW - Hepatitis, Animal -- pathology KW - Hepatitis, Animal -- chemically induced KW - Hepatitis, Animal -- immunology KW - Interferon-gamma -- metabolism KW - Interferon-gamma -- pharmacology KW - T-Lymphocytes -- immunology KW - Signal Transduction KW - Phosphoproteins -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66951083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=IFN-gamma%2FSTAT1+acts+as+a+proinflammatory+signal+in+T+cell-mediated+hepatitis+via+induction+of+multiple+chemokines+and+adhesion+molecules%3A+a+critical+role+of+IRF-1.&rft.au=Jaruga%2C+Barbara%3BHong%2C+Feng%3BKim%2C+Won-Ho%3BGao%2C+Bin&rft.aulast=Jaruga&rft.aufirst=Barbara&rft.date=2004-11-01&rft.volume=287&rft.issue=5&rft.spage=G1044&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 - 2004-11-24 N1 - Date created - 2004-10-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. AN - 66922164; 15457404 AB - Catechol-O-methyltransferase (COMT) is a key enzyme in the elimination of dopamine in the prefrontal cortex of the human brain. Genetic variation in the COMT gene (MIM 116790) has been associated with altered prefrontal cortex function and higher risk for schizophrenia, but the specific alleles and their functional implications have been controversial. We analyzed the effects of several single-nucleotide polymorphisms (SNPs) within COMT on mRNA expression levels (using reverse-transcriptase polymerase chain reaction analysis), protein levels (using Western blot analysis), and enzyme activity (using catechol methylation) in a large sample (n = 108) of postmortem human prefrontal cortex tissue, which predominantly expresses the -membrane-bound isoform. A common coding SNP, Val158Met (rs4680), significantly affected protein abundance and enzyme activity but not mRNA expression levels, suggesting that differences in protein integrity account for the difference in enzyme activity between alleles. A SNP in intron 1 (rs737865) and a SNP in the 3' flanking region (rs165599)--both of which have been reported to contribute to allelic expression differences and to be associated with schizophrenia as part of a haplotype with Val--had no effect on mRNA expression levels, protein immunoreactivity, or enzyme activity. In lymphocytes from 47 subjects, we confirmed a similar effect on enzyme activity in samples with the Val/Met genotype but no effect in samples with the intron 1 or 3' SNPs. Separate analyses revealed that the subject's sex, as well as the presence of a SNP in the P2 promoter region (rs2097603), had small effects on COMT enzyme activity. Using site-directed mutagenesis of mouse COMT cDNA, followed by in vitro translation, we found that the conversion of Leu at the homologous position into Met or Val progressively and significantly diminished enzyme activity. Thus, although we cannot exclude a more complex genetic basis for functional effects of COMT, Val is a predominant factor that determines higher COMT activity in the prefrontal cortex, which presumably leads to lower synaptic dopamine levels and relatively deleterious prefrontal function. JF - American journal of human genetics AU - Chen, Jingshan AU - Lipska, Barbara K AU - Halim, Nader AU - Ma, Quang D AU - Matsumoto, Mitsuyuki AU - Melhem, Samer AU - Kolachana, Bhaskar S AU - Hyde, Thomas M AU - Herman, Mary M AU - Apud, Jose AU - Egan, Michael F AU - Kleinman, Joel E AU - Weinberger, Daniel R AD - Clinical Brain Disorders Branch, Genes, Cognition, and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 807 EP - 821 VL - 75 IS - 5 SN - 0002-9297, 0002-9297 KW - DNA Primers KW - 0 KW - Proteins KW - RNA, Messenger KW - Catechol O-Methyltransferase KW - EC 2.1.1.6 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Genotype KW - Animals KW - Polymorphism, Single Nucleotide KW - Blotting, Western KW - Analysis of Variance KW - Sex Factors KW - Humans KW - Lymphocytes -- enzymology KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Methylation KW - Genetic Variation KW - Catechol O-Methyltransferase -- genetics KW - RNA, Messenger -- metabolism KW - Prefrontal Cortex -- enzymology KW - Prefrontal Cortex -- pathology KW - Gene Expression Regulation, Enzymologic -- physiology KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66922164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+human+genetics&rft.atitle=Functional+analysis+of+genetic+variation+in+catechol-O-methyltransferase+%28COMT%29%3A+effects+on+mRNA%2C+protein%2C+and+enzyme+activity+in+postmortem+human+brain.&rft.au=Chen%2C+Jingshan%3BLipska%2C+Barbara+K%3BHalim%2C+Nader%3BMa%2C+Quang+D%3BMatsumoto%2C+Mitsuyuki%3BMelhem%2C+Samer%3BKolachana%2C+Bhaskar+S%3BHyde%2C+Thomas+M%3BHerman%2C+Mary+M%3BApud%2C+Jose%3BEgan%2C+Michael+F%3BKleinman%2C+Joel+E%3BWeinberger%2C+Daniel+R&rft.aulast=Chen&rft.aufirst=Jingshan&rft.date=2004-11-01&rft.volume=75&rft.issue=5&rft.spage=807&rft.isbn=&rft.btitle=&rft.title=American+journal+of+human+genetics&rft.issn=00029297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-03 N1 - Date created - 2004-09-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 2003 May 13;100(10):6186-91 [12716966] J Biol Chem. 2003 Mar 28;278(13):11546-53 [12540849] Neuropsychopharmacology. 2003 Aug;28(8):1521-30 [12799619] Mol Psychiatry. 2003 Sep;8(9):797-810 [12931207] Arch Gen Psychiatry. 2003 Sep;60(9):889-96 [12963670] Synapse. 2004 Feb;51(2):112-8 [14618678] Am J Psychiatry. 2004 Jan;161(1):125-32 [14702260] Am J Psychiatry. 2004 Feb;161(2):359-61 [14754787] Mol Psychiatry. 2004 Feb;9(2):151-60 [14966473] Mol Psychiatry. 2004 Mar;9(3):299-307 [14569272] Breast Cancer Res Treat. 2004 May;85(2):121-31 [15111770] J Neurosci. 2004 Jun 9;24(23):5331-5 [15190105] Psychopharmacology (Berl). 2004 Jun;174(1):3-16 [15118803] Mol Psychiatry. 2004 Sep;9(9):859-70 [15098000] Am J Hum Genet. 1977 Mar;29(2):125-35 [848488] Science. 1979 Jan 5;203(4375):63-5 [758679] Clin Genet. 1981 May;19(5):426-37 [7296933] Am J Med Genet. 1981;10(3):279-90 [7304673] Biochem Genet. 1981 Dec;19(11-12):1037-53 [7337686] J Neurochem. 1982 Jan;38(1):191-5 [7108526] Clin Pharmacol Ther. 1990 Oct;48(4):381-9 [2225698] DNA Cell Biol. 1993 Apr;12(3):253-63 [8466648] J Neurochem. 1993 Aug;61(2):637-47 [8336146] Nature. 1994 Mar 24;368(6469):354-8 [8127373] Biochemistry. 1995 Apr 4;34(13):4202-10 [7703232] Biochim Biophys Acta. 1995 Aug 16;1251(1):1-10 [7647086] Biotechniques. 1997 Apr;22(4):624-6, 628, 630 [9105609] J Neurosci. 1998 Apr 1;18(7):2697-708 [9502827] Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9991-6 [9707588] Annu Rev Pharmacol Toxicol. 1999;39:19-52 [10331075] J Biol Chem. 1958 Sep;233(3):702-5 [13575440] Mol Psychiatry. 2005 Jan;10(1):40-68; image 5 [15263907] Am J Hum Genet. 2003 Jul;73(1):152-61 [12802784] Nat Struct Biol. 2001 Mar;8(3):271-9 [11224575] J Comp Neurol. 2001 Mar 26;432(1):119-36 [11241381] Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6917-22 [11381111] Biol Psychiatry. 2001 Dec 1;50(11):825-44 [11743939] Eur J Neurosci. 2002 Jan;15(2):246-56 [11849292] Mol Psychiatry. 2002;7(4):405-11 [11986984] Hum Genet. 2002 Dec;111(6):521-37 [12436243] J Pharmacol Exp Ther. 2002 Dec;303(3):1309-16 [12438556] Am J Hum Genet. 2002 Dec;71(6):1296-302 [12402217] Psychiatr Genet. 2003 Mar;13(1):33-41 [12605099] Protein Eng. 2003 Jan;16(1):19-25 [12646689] Erratum In: Am J Hum Genet. 2005 Jun;76(6):1089 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Global gene expression profiles of human head and neck squamous carcinoma cell lines. AN - 66852555; 15352037 AB - For genomewide monitoring and identification of biomarkers of head and neck squamous cell carcinoma (HNSCC), we have conducted a systematic characterization of gene expression profiles, using human cDNA microarrays containing 9K clones, in 25 HNSCC cell lines and 1 immortalized human oral keratinocyte cell line. We used normal human oral keratinocytes (NHOKs) as a reference. Our study showed that genes primarily involved in cell cycle regulation, oncogenesis, cell proliferation, differentiation, apoptosis and cell adhesion were widely altered in the 26 cell lines. Upregulated genes included known oncogenes, protein kinases, DNA-binding proteins and cell cycle regulators, while those commonly downregulated included differentiation markers, cell adhesion proteins, extracellular matrix proteins, structural proteins (keratins) and protease inhibitor proteins. Compared to NHOK, we observed a striking reduction in the expression of genes involved in terminal differentiation, suggesting that a loss in this process is an important signature of HNSCC. In addition, hierarchical clustering analysis as well as principal component analysis revealed 2 distinctive subtypes of gene expression patterns among the 26 cell lines, reflecting a degree of heterogeneity in HNSCC. By applying significance analysis of microarrays, 128 genes were selected for being distinctively expressed between the 2 groups. Genes differentially expressed in the 2 subgroups include cell proliferation-related genes, IGFBP6, EGFR and VEGFC; tumor suppression and apoptosis-related genes such as Tp53, Tp63; as well as cell cycle regulators such as CCND1 and CCND2 (cyclins D1 and D2), suggesting that the 2 subgroups might have undergone different pathways of carcinogenesis. JF - International journal of cancer AU - Jeon, Geoung A AU - Lee, Ju-Seog AU - Patel, Vyomesh AU - Gutkind, J Silvio AU - Thorgeirsson, Snorri S AU - Kim, Eun Cheol AU - Chu, In-Sun AU - Amornphimoltham, Panomwat AU - Park, Myung Hee AD - Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIDCR, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/11/01/ PY - 2004 DA - 2004 Nov 01 SP - 249 EP - 258 VL - 112 IS - 2 SN - 0020-7136, 0020-7136 KW - Biomarkers, Tumor KW - 0 KW - Neoplasm Proteins KW - Index Medicus KW - Apoptosis KW - Tumor Cells, Cultured KW - Genes, Tumor Suppressor KW - Humans KW - Keratinocytes KW - Cell Cycle KW - Cell Division KW - Cell Adhesion KW - Neoplasm Proteins -- biosynthesis KW - Gene Expression Profiling KW - Carcinoma, Squamous Cell -- pathology KW - Carcinoma, Squamous Cell -- genetics KW - Biomarkers, Tumor -- analysis KW - Head and Neck Neoplasms -- pathology KW - Head and Neck Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66852555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Global+gene+expression+profiles+of+human+head+and+neck+squamous+carcinoma+cell+lines.&rft.au=Jeon%2C+Geoung+A%3BLee%2C+Ju-Seog%3BPatel%2C+Vyomesh%3BGutkind%2C+J+Silvio%3BThorgeirsson%2C+Snorri+S%3BKim%2C+Eun+Cheol%3BChu%2C+In-Sun%3BAmornphimoltham%2C+Panomwat%3BPark%2C+Myung+Hee&rft.aulast=Jeon&rft.aufirst=Geoung&rft.date=2004-11-01&rft.volume=112&rft.issue=2&rft.spage=249&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 - 2004-10-05 N1 - Date created - 2004-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicology and carcinogenesis studies of microencapsulated trans-cinnamaldehyde in rats and mice. AN - 66849769; 15350673 AB - trans-Cinnamaldehyde is a widely used natural ingredient that is added to foods and cosmetics as a flavoring and fragrance agent. Male and female F344/N rats and B6C3F(1) mice were exposed to microencapsulated trans-cinnamaldehyde in the feed for three months or two years. All studies included untreated and vehicle control groups. In the three-month studies, rats and mice were given diets containing 4100, 8200, 16,500, or 33,000 ppm trans-cinnamaldehyde. In rats, feed consumption was reduced in all exposed groups. In mice, feed consumption was reduced in the highest dose groups. Body weights of all treated males were less than controls. Body weights were reduced in female rats exposed to 16,500 or 33,000 ppm and female mice exposed to 8200 ppm or greater. All rats survived to the end of the study but some male mice in the highest dose groups died due to inanition from unpalatability of the dosed feed. The incidence of squamous epithelial hyperplasia of the forestomach was significantly increased in rats exposed to 8200 ppm or greater and female mice exposed to 33,000 ppm. In mice, the incidence of olfactory epithelial degeneration of the nasal cavity was significantly increased in males and females exposed to 16,500 ppm and females exposed to 33,000 ppm. In the two-year studies, rats and mice were exposed to 1000, 2100, or 4100 ppm trans-cinnamaldehyde. Body weights were reduced in mice exposed to 2100 ppm and in rats and mice exposed to 4100 ppm. In rats, hippuric acid excretion was dose proportional indicating that absorption, metabolism, and excretion were not saturated. No neoplasms were attributed to trans-cinnamaldehyde in rats or mice. Squamous cell papillomas and carcinomas of the forestomach were observed in male and female mice but the incidences were within the NTP historical control range and were not considered to be related to trans-cinnamaldehyde exposure. JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association AU - Hooth, M J AU - Sills, R C AU - Burka, L T AU - Haseman, J K AU - Witt, K L AU - Orzech, D P AU - Fuciarelli, A F AU - Graves, S W AU - Johnson, J D AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Mail Drop EC-35, 79 TW Alexander Drive, Research Triangle Park, NC 27709, USA. hooth@niehs.nih.gov Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 1757 EP - 1768 VL - 42 IS - 11 SN - 0278-6915, 0278-6915 KW - Carcinogens KW - 0 KW - Flavoring Agents KW - Acrolein KW - 7864XYD3JJ KW - cinnamic aldehyde KW - SR60A3XG0F KW - Index Medicus KW - Administration, Oral KW - Animals KW - Drug Compounding KW - Dose-Response Relationship, Drug KW - Random Allocation KW - Mice KW - Longitudinal Studies KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Body Weight -- drug effects KW - Carcinogenicity Tests KW - Female KW - Male KW - Survival Analysis KW - Stomach -- pathology KW - Flavoring Agents -- toxicity KW - Acrolein -- analogs & derivatives KW - Carcinogens -- toxicity KW - Stomach -- drug effects KW - Acrolein -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66849769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.atitle=Toxicology+and+carcinogenesis+studies+of+microencapsulated+trans-cinnamaldehyde+in+rats+and+mice.&rft.au=Hooth%2C+M+J%3BSills%2C+R+C%3BBurka%2C+L+T%3BHaseman%2C+J+K%3BWitt%2C+K+L%3BOrzech%2C+D+P%3BFuciarelli%2C+A+F%3BGraves%2C+S+W%3BJohnson%2C+J+D%3BBucher%2C+J+R&rft.aulast=Hooth&rft.aufirst=M&rft.date=2004-11-01&rft.volume=42&rft.issue=11&rft.spage=1757&rft.isbn=&rft.btitle=&rft.title=Food+and+chemical+toxicology+%3A+an+international+journal+published+for+the+British+Industrial+Biological+Research+Association&rft.issn=02786915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-21 N1 - Date created - 2004-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs. AN - 66754710; 15292713 AB - CCI-779 is an ester of the immunosuppressive agent sirolimus (rapamycin) that causes cell-cycle arrest at G1 via inhibition of key signaling pathways resulting in inhibition of RNA translation. Antitumor activity has been demonstrated using cell lines and animal models of malignant glioma. Patients receiving enzyme-inducing anti-epileptic drugs (EIAEDs) can have altered metabolism of drugs like CCI-779 that are metabolized through the hepatic cytochrome P450 enzyme system. The objectives of this study were to determine the pharmacokinetic profile and the maximum tolerated dose of CCI-779 in patients with recurrent malignant gliioma taking EIAEDs. The starting dose of CCI-779 was 250 mg intravenously (IV) administered weekly on a continuous basis. Standard dose escalation was performed until the maximum tolerated dose was established. Toxicity was assessed using the National Cancer Institute common toxicity criteria. Two of 6 patients treated at the second dose level of 330 mg sustained a dose-limiting toxicity: grade III stomatitis, grade 3 hypercholesterolemia, or grade 4 hypertriglyceridemia. The maximum tolerated dose was reached at 250 mg IV. Pharmacokinetic profiles were similar to those previously described, but the area under the whole blood concentration-time curve of rapamycin was 1.6 fold lower for patients on EIAEDs. The recommended phase II dose of CCI 779 for patients on enzyme-inducing antiepileptic drugs is 250 mg IV weekly. A phase II study is ongoing to determine the efficacy of this agent. JF - Investigational new drugs AU - Chang, Susan M AU - Kuhn, John AU - Wen, Patrick AU - Greenberg, Harry AU - Schiff, David AU - Conrad, Charles AU - Fink, Karen AU - Robins, H Ian AU - Cloughesy, Timothy AU - De Angelis, Lisa AU - Razier, Jeffrey AU - Hess, Kenneth AU - Dancey, Janet AU - Prados, Michael D AU - North American Brain Tumor Consortium And The National Cancer Institute AD - Neuro-Oncology Service, University of California, San Francisco, CA 94143, USA. changs@neurosurg.ucsf.edu ; North American Brain Tumor Consortium And The National Cancer Institute Y1 - 2004/11// PY - 2004 DA - November 2004 SP - 427 EP - 435 VL - 22 IS - 4 SN - 0167-6997, 0167-6997 KW - Anticonvulsants KW - 0 KW - Antineoplastic Agents KW - temsirolimus KW - 624KN6GM2T KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Sirolimus KW - W36ZG6FT64 KW - Index Medicus KW - Drug Administration Schedule KW - Drug Interactions KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Anticonvulsants -- toxicity KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Anticonvulsants -- administration & dosage KW - Anticonvulsants -- pharmacokinetics KW - Adult KW - Cohort Studies KW - Treatment Outcome KW - Enzyme Induction KW - Middle Aged KW - Neoplasm Recurrence, Local KW - Maximum Tolerated Dose KW - Male KW - Female KW - Sirolimus -- administration & dosage KW - Glioma -- drug therapy KW - Brain Neoplasms -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- pharmacokinetics KW - Antineoplastic Agents -- toxicity KW - Sirolimus -- pharmacokinetics KW - Sirolimus -- toxicity KW - Sirolimus -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66754710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigational+new+drugs&rft.atitle=Phase+I%2Fpharmacokinetic+study+of+CCI-779+in+patients+with+recurrent+malignant+glioma+on+enzyme-inducing+antiepileptic+drugs.&rft.au=Chang%2C+Susan+M%3BKuhn%2C+John%3BWen%2C+Patrick%3BGreenberg%2C+Harry%3BSchiff%2C+David%3BConrad%2C+Charles%3BFink%2C+Karen%3BRobins%2C+H+Ian%3BCloughesy%2C+Timothy%3BDe+Angelis%2C+Lisa%3BRazier%2C+Jeffrey%3BHess%2C+Kenneth%3BDancey%2C+Janet%3BPrados%2C+Michael+D%3BNorth+American+Brain+Tumor+Consortium+And+The+National+Cancer+Institute&rft.aulast=Chang&rft.aufirst=Susan&rft.date=2004-11-01&rft.volume=22&rft.issue=4&rft.spage=427&rft.isbn=&rft.btitle=&rft.title=Investigational+new+drugs&rft.issn=01676997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-09-07 N1 - Date created - 2004-08-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunogenetic differences between Caucasian women with and those without silicone implants in whom myositis develops AN - 19936382; 6073645 AB - To determine whether patients in whom myositis develops after they receive silicone breast implants have distinct clinical, serologic, and/or immunogenetic features compared with patients with myositis who do not have silicone implants. A preliminary case series study was followed by a larger, independent, matched case-control study to evaluate women in whom myositis developed after they received silicone implants (MASI patients) compared with healthy women with silicone implants and women with myositis but without silicone implants (idiopathic inflammatory myopathy; IIM patients). In a preliminary study, 11 MASI patients differed from 76 IIM patients in having an increased frequency of HLA-DQA1*0102 (odds ratio [OR] 9.8, 95% confidence interval [95% CI] 1.77-96.79) and decreased frequencies of the myositis-associated risk factor DRB1*0301 (OR 0.1 [95% CI 0.002-0.63]) and its linked allele DQA1*0501 (OR 0.2 [95% CI 0.02- 0.87]). A subsequent independent, matched case-control study revealed that although clinical features and autoantibodies did not differ significantly between the MASI and IIM groups, MASI patients again had decreased frequencies of DRB1*0301 (OR 0.2 [95% CI 0.07-0.72]) and DQA1*0501 (OR 0.2 [95% CI 0.08- 0.84]) compared with IIM patients. Additional comparisons between MASI patients from both studies combined (n = 37) and a larger population of IIM patients (n = 453) suggested that HLA-DQA1*0102 may be uniquely associated with MASI (OR 2.6 [95% CI 1.25-5.46]). Women in whom inflammatory myopathy develops after they receive silicone implants constitute an immunogenetically distinct group of patients with myositis. These and other data suggest that autoimmune diseases as now defined may consist of multiple distinct entities, each of which is characterized by different genes and environmental exposures. JF - Arthritis & Rheumatism AU - O'Hanlon, Terrance AU - Koneru, Bhanu AU - Bayat, Elham AU - Love, Lori AU - Targoff, Ira AU - Malley, James AU - Malley, Karen AU - Miller, Frederick AD - National Institute of Environmental Health Sciences, NIH, Bethesda, MD, ohanlon@niehs.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 3646 EP - 3650 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 50 IS - 11 SN - 0004-3591, 0004-3591 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts; Immunology Abstracts KW - Histocompatibility antigen HLA KW - Myositis KW - Immunogenetics KW - Data processing KW - Silicones KW - Autoantibodies KW - Risk factors KW - Autoimmune diseases KW - Inflammation KW - Myopathy KW - G 07880:Human Genetics KW - F 06930:Autoimmunity KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19936382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+%26+Rheumatism&rft.atitle=Immunogenetic+differences+between+Caucasian+women+with+and+those+without+silicone+implants+in+whom+myositis+develops&rft.au=O%27Hanlon%2C+Terrance%3BKoneru%2C+Bhanu%3BBayat%2C+Elham%3BLove%2C+Lori%3BTargoff%2C+Ira%3BMalley%2C+James%3BMalley%2C+Karen%3BMiller%2C+Frederick&rft.aulast=O%27Hanlon&rft.aufirst=Terrance&rft.date=2004-11-01&rft.volume=50&rft.issue=11&rft.spage=3646&rft.isbn=&rft.btitle=&rft.title=Arthritis+%26+Rheumatism&rft.issn=00043591&rft_id=info:doi/10.1002%2Fart.20587 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-06-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Histocompatibility antigen HLA; Myositis; Data processing; Immunogenetics; Autoantibodies; Silicones; Risk factors; Autoimmune diseases; Myopathy; Inflammation DO - http://dx.doi.org/10.1002/art.20587 ER - TY - JOUR T1 - Metallothionein-I/II Double Knockout Mice Are Hypersensitive to Lead-Induced Kidney Carcinogenesis: Role of Inclusion Body Formation AN - 19815487; 6077466 AB - Lead is an environmental nephrotoxicant and probable human carcinogen. Elucidating factors predisposing populations to lead toxicity is an important public health issue. Recently, we found that metallothionein-I/-II double knockout (metallothionein-null) mice that are unable to produce the major forms of metallothionein do not produce lead inclusion bodies, which are thought to mitigate lead toxicity, and were sensitive to the subchronic toxic effects of lead exposure (10 weeks), showing modestly diminished renal function and nephromegaly compared with wild-type (WT) mice. It is unclear how this knockout might impact lead carcinogenesis. Thus, the effects of lead(II) acetate were tested in groups (n = 25) of male metallothionein-null and WT mice receiving drinking water with 0, 1,000, 2,000, or 4,000 parts per million lead for up to 104 weeks. Renal proliferative lesions (adenoma and cystic tubular atypical hyperplasia) were much more common and more severe in lead-exposed metallothionein-null mice than in WT mice. A metastatic renal cell carcinoma also occurred in a lead-treated metallothionein-null mouse, whereas none occurred in WT mice. Lead-induced renal proliferative lesions showed marked overexpression of cyclin D1, a common feature of human renal tumors. Renal lead- containing nuclear inclusion bodies were frequently observed in WT mice but did not form in metallothionein-null mice. Metallothionein was often found associated with the outer portion of these inclusion bodies. Thus, the metallothionein-null mice cannot form renal inclusion bodies, even after protracted lead exposure, and this increases the carcinogenic potential of lead. Poor production of metallothionein may predispose human populations to lead carcinogenicity. JF - Cancer Research AU - Waalkes, Michael P AU - Liu, Jie AU - Goyer, Robert A AU - Diwan, Bhalchandra A AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina Y1 - 2004/11/01/ PY - 2004 DA - 2004 Nov 01 SP - 7766 EP - 7772 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 64 IS - 21 SN - 0008-5472, 0008-5472 KW - Toxicology Abstracts KW - Metallothionein KW - Tumors KW - Toxicity KW - Carcinogens KW - Acetic acid KW - Lead KW - Public health KW - Metastases KW - Hyperplasia KW - Renal function KW - renal cell carcinoma KW - Carcinogenesis KW - Inclusion bodies KW - Drinking water KW - Adenoma KW - cyclin D1 KW - X 24360:Metals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19815487?accountid=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+Research&rft.atitle=Metallothionein-I%2FII+Double+Knockout+Mice+Are+Hypersensitive+to+Lead-Induced+Kidney+Carcinogenesis%3A+Role+of+Inclusion+Body+Formation&rft.au=Waalkes%2C+Michael+P%3BLiu%2C+Jie%3BGoyer%2C+Robert+A%3BDiwan%2C+Bhalchandra+A&rft.aulast=Waalkes&rft.aufirst=Michael&rft.date=2004-11-01&rft.volume=64&rft.issue=21&rft.spage=7766&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 - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Metallothionein; Carcinogens; Toxicity; Tumors; Acetic acid; Lead; Public health; Metastases; Hyperplasia; renal cell carcinoma; Renal function; Carcinogenesis; Inclusion bodies; Drinking water; Adenoma; cyclin D1 ER - TY - JOUR T1 - Phloridzin Improves Hyperglycemia But Not Hepatic Insulin Resistance in a Transgenic Mouse Model of Type 2 Diabetes AN - 19805209; 6061690 AB - The chronic hyperglycemia that occurs in type 2 diabetes may cause deterioration of beta-cell function and insulin resistance in peripheral tissues. Mice that express a dominant-negative IGF-1 receptor, specifically in skeletal muscle (MKR mice), exhibit severe insulin resistance, hyperinsulinemia, dyslipidemia, and hyper-glycemia. To determine the role of hyperglycemia in the worsening of the diabetes state in these animals, MKR mice were treated with phloridzin (PHZ), which inhibits intestinal glucose uptake and renal glucose reabsorption. Blood glucose levels were decreased and urine glucose levels were increased in response to PHZ treatment in MKR mice. PHZ treatment also increased food intake in MKR mice; however, the fat mass was decreased and lean body mass did not change. Serum insulin, fatty acid, and triglyceride levels were not affected by PHZ treatment in MKR mice. Hyperinsulinemic-euglycemic clamp analysis demonstrated that glucose uptake in white adipose tissue was significantly increased in response to PHZ treatment. Despite the reduction in blood glucose following PHZ treatment, there was no improvement in insulin- stimulated whole-body glucose uptake in MKR mice and neither was there suppression of endogenous glucose production by insulin. These results suggest that glucotoxicity plays little or no role in the worsening of insulin resistance that occurs in the MKR mouse model of type 2 diabetes. JF - Diabetes AU - Zhao, Hong AU - Yakar, Shoshana AU - Gavrilova, Oksana AU - Sun, Hui AU - Zhang, Yang AU - Kim, Hyunsook AU - Setser, Jennifer AU - Jou, William AU - Leroith, Derek AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. Mouse Metabolic Core Facility, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 2901 EP - 2909 VL - 53 IS - 11 SN - 0012-1797, 0012-1797 KW - Biotechnology and Bioengineering Abstracts KW - Insulin-like growth factor I KW - Animal models KW - Glucose KW - Hyperinsulinemia KW - Transgenic mice KW - Insulin KW - Diabetes mellitus KW - Blood KW - Hyperglycemia KW - Urine KW - Food intake KW - Triglycerides KW - Dyslipidemia KW - Kidney KW - Fatty acids KW - Liver KW - Intestine KW - Adipose tissue KW - Body fat KW - Skeletal muscle KW - Lean body mass KW - Reabsorption KW - W 30935:Food Biotechnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19805209?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes&rft.atitle=Phloridzin+Improves+Hyperglycemia+But+Not+Hepatic+Insulin+Resistance+in+a+Transgenic+Mouse+Model+of+Type+2+Diabetes&rft.au=Zhao%2C+Hong%3BYakar%2C+Shoshana%3BGavrilova%2C+Oksana%3BSun%2C+Hui%3BZhang%2C+Yang%3BKim%2C+Hyunsook%3BSetser%2C+Jennifer%3BJou%2C+William%3BLeroith%2C+Derek&rft.aulast=Zhao&rft.aufirst=Hong&rft.date=2004-11-01&rft.volume=53&rft.issue=11&rft.spage=2901&rft.isbn=&rft.btitle=&rft.title=Diabetes&rft.issn=00121797&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 - Insulin-like growth factor I; Glucose; Animal models; Hyperinsulinemia; Transgenic mice; Insulin; Diabetes mellitus; Blood; Hyperglycemia; Food intake; Urine; Triglycerides; Dyslipidemia; Intestine; Liver; Fatty acids; Kidney; Body fat; Adipose tissue; Skeletal muscle; Lean body mass; Reabsorption ER - TY - JOUR T1 - Antimicrobial proteins act as "alarmins" in joint immune defense AN - 19726173; 6073615 AB - No abstract. JF - Arthritis & Rheumatism AU - Yang, De AU - Oppenheim, Joost J AD - Science Applications and International Corporation-Frederick, Center for Cancer Research, National Cancer Institute, NIH, Frederick, Maryland, dyang@mail.ncifcrf.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 3401 EP - 3403 PB - John Wiley & Sons, Ltd., Baffins Lane Chichester W. Sussex PO19 1UD UK, [mailto:customer@wiley.co.uk], [URL:http://www.wiley.com/] VL - 50 IS - 11 SN - 0004-3591, 0004-3591 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Immunology Abstracts KW - Joint diseases KW - Antimicrobial agents KW - A 01340:Antibiotics & Antimicrobials KW - F 06930:Autoimmunity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19726173?accountid=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=Arthritis+%26+Rheumatism&rft.atitle=Antimicrobial+proteins+act+as+%22alarmins%22+in+joint+immune+defense&rft.au=Yang%2C+De%3BOppenheim%2C+Joost+J&rft.aulast=Yang&rft.aufirst=De&rft.date=2004-11-01&rft.volume=50&rft.issue=11&rft.spage=3401&rft.isbn=&rft.btitle=&rft.title=Arthritis+%26+Rheumatism&rft.issn=00043591&rft_id=info:doi/10.1002%2Fart.20604 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-12-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Joint diseases; Antimicrobial agents DO - http://dx.doi.org/10.1002/art.20604 ER - TY - JOUR T1 - Correcting log ratios for signal saturation in cDNA microarrays AN - 19697140; 6076892 AB - MOTIVATION: Pixel saturation occurs when the pixel intensity exceeds a threshold and the recorded pixel intensity is truncated. Microarray experiments are commonly afflicted with saturated pixels. As a result, estimators of gene expression are biased, with the amount of bias increasing as a function of the proportion of pixels saturated. Saturation is directly related to the photomultiplier tube (PMT) voltage settings and RNA abundance and is not necessarily associated with poor array or poor spot quality. When choosing PMT settings, higher PMT settings are desired because of improved signal-to-noise ratios of low-intensity spots. This improved signal is somewhat offset by saturation of high-intensity spots. In practice, spots with saturated pixels are discarded or the biased value is used. Neither of these approaches is appealing, particularly the former approach when a highly expressed gene is discarded because of saturation. RESULTS: We present a method to correct for saturation using pixel-level data. The method is based on a censored regression model. Evaluations on several arrays indicate that the method performs well. Simulation studies suggest that the method is robust under certain model violations. Supplementary material: Supplementary tables and figures can be found at http://linus.nci.nih.gov/Data/doddl/saturation/extras.pdf JF - Bioinformatics AU - Dodd, Lori E AU - Korn, Edward L AU - Mcshane, Lisa M AU - Chandramouli, GVR AU - Chuang, Eric Y AD - Biometric Research Branch, DCTD, National Cancer Institute, Bethesda, MD Y1 - 2004/11/01/ PY - 2004 DA - 2004 Nov 01 SP - 2685 EP - 2693 PB - Oxford University Press, [URL:http://www3.oup.co.uk/jnls/] VL - 20 IS - 16 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Mathematical models KW - DNA microarrays KW - Gene expression KW - RNA KW - Regression analysis KW - Bioinformatics KW - W 30965:Miscellaneous, Reviews KW - W4 350:Bioinformatics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19697140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Correcting+log+ratios+for+signal+saturation+in+cDNA+microarrays&rft.au=Dodd%2C+Lori+E%3BKorn%2C+Edward+L%3BMcshane%2C+Lisa+M%3BChandramouli%2C+GVR%3BChuang%2C+Eric+Y&rft.aulast=Dodd&rft.aufirst=Lori&rft.date=2004-11-01&rft.volume=20&rft.issue=16&rft.spage=2685&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Mathematical models; Bioinformatics; Gene expression; Regression analysis; RNA; DNA microarrays ER - TY - JOUR T1 - Modulatory Effects of l-Carnitine on Glucocorticoid Receptor Activity AN - 19418306; 6116981 AB - l-Carnitine (3-hydroxy-4-N,N,N-trimethylaminobutyrate) is a conditionally essential nutrient with a major role in cellular energy metabolism. It is available in the United States as both a prescription drug and an over-the- counter nutritional supplement. Accumulating evidence from both animal and human studies indicates that pharmacologic doses of l-carnitine (LCAR) have immunomodulatory effects resembling those of glucocorticoids (GC). On the other hand, in contrast to GC, which cause bone loss, LCAR seems to have positive effects on bone metabolism. To explore the molecular bases of this GC-like activity of LCAR, we investigated its effects on glucocorticoid receptor (GR)- modulated cytokine release ex vivo, and on the transcriptional activity, intracellular trafficking, and binding of GR in vitro. At high noncytotoxic doses, LCAR (a) suppressed the lipopolysaccharide-stimulated release of tumor necrosis factor alpha and interleukin-12 from primary human monocytes in a GC-like fashion, (b) stimulated the transcriptional activity of GR on the GC-responsive promoters, (c) triggered nuclear translocation of green fluorescent protein (GFP)-fused GR, and (d) reduced the whole cell binding of [ super(3)H]-dexamethasone to GR. These results suggest that LCAR is a "nutritional modulator" of the GR, by acting as an agonist-like compound. Since LCAR appears to have positive effects on bone metabolism, in contrast to GC, LCAR may share some of the therapeutic properties of GC, particularly on the immune system, but not their deleterious side effects on some of other organs/tissues. Thus, LCAR is potentially a useful alternative compound of GC in particular therapeutic situations. The clinical and therapeutic implications of these findings, as well as a better understanding of their mechanisms, warrant further research. JF - Annals of the New York Academy of Sciences AU - Manoli, Irini AU - De Martino, Massimo U AU - Kino, Tomoshige AU - Alesci, Salvatore AD - Endocrine Section, Laboratory of Clinical Investigation, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 147 EP - 157 PB - The New York Academy of Sciences VL - 1033 SN - 0077-8923, 0077-8923 KW - Health & Safety Science Abstracts; Immunology Abstracts KW - immune system KW - Immune system KW - Green fluorescent protein KW - L-Carnitine KW - tumors KW - Nutrients KW - Nutrition KW - Interleukin 12 KW - Promoters KW - Nuclear transport KW - Monocytes KW - Drugs KW - Energy metabolism KW - trafficking KW - Transcription KW - Organs KW - Glucocorticoids KW - Bone KW - Glucocorticoid receptors KW - Dietary supplements KW - Bone loss KW - Proteins KW - Bone turnover KW - translocation KW - Tumor necrosis factor- alpha KW - Metabolism KW - Side effects KW - F 06955:Immunomodulation & Immunopharmacology KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19418306?accountid=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=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Modulatory+Effects+of+l-Carnitine+on+Glucocorticoid+Receptor+Activity&rft.au=Manoli%2C+Irini%3BDe+Martino%2C+Massimo+U%3BKino%2C+Tomoshige%3BAlesci%2C+Salvatore&rft.aulast=Manoli&rft.aufirst=Irini&rft.date=2004-11-01&rft.volume=1033&rft.issue=&rft.spage=147&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 revised - 2007-04-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Energy metabolism; Immune system; L-Carnitine; Green fluorescent protein; Transcription; Nutrients; Glucocorticoids; Nuclear transport; Promoters; Interleukin 12; Glucocorticoid receptors; Dietary supplements; Bone loss; Bone turnover; Monocytes; Tumor necrosis factor- alpha; Drugs; Side effects; Bone; immune system; trafficking; Proteins; tumors; translocation; Organs; Nutrition; Metabolism ER - TY - JOUR T1 - Temporal Analysis of Coxiella burnetii Morphological Differentiation AN - 18063158; 6062423 AB - Coxiella burnetii undergoes a poorly defined developmental cycle that generates morphologically distinct small-cell variants (SCV) and large-cell variants (LCV). We developed a model to study C. burnetii morphogenesis that uses Vero cells synchronously infected with homogeneous SCV (Nine Mile strain in phase II) harvested from aged infected cell cultures. A time course transmission electron microscopic analysis over 8 days of intracellular growth was evaluated in conjunction with one-step growth curves to correlate morphological differentiations with growth cycle phase. Lag phase occurred during the first 2 days postinfection (p.i.) and was primarily composed of SCV-to-LCV morphogenesis. LCV forms predominated over the next 4 days, during which exponential growth was observed. Calculated generation times during exponential phase were 10.2 h (by quantitative PCR assay) and 11.7 h (by replating fluorescent focus-forming unit assay). Stationary phase began at approximately 6 days p.i. and coincided with the reappearance of SCV, which increased in number at 8 days p.i. Quantitative reverse transcriptase-PCR demonstrated maximal expression of scvA, which encodes an SCV-specific protein, at 8 days p.i., while immunogold transmission electron microscopy revealed degradation of ScvA throughout lag and exponential phases, with increased expression observed at the onset of stationary phase. Collectively, these results indicate that the overall growth cycle of C. burnetii is characteristic of a closed bacterial system and that the replicative form of the organism is the LCV. The experimental model described in this report will allow a global transcriptome and proteome analysis of C. burnetii developmental forms. JF - Journal of Bacteriology AU - Coleman, Sherry A AU - Fischer, Elizabeth R AU - Howe, Dale AU - Mead, David J AU - Heinzen, Robert A AD - Coxiella Pathogenesis Unit, Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana Y1 - 2004/11/01/ PY - 2004 DA - 2004 Nov 01 SP - 7344 EP - 7352 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 186 IS - 21 SN - 0021-9193, 0021-9193 KW - Microbiology Abstracts B: Bacteriology KW - Lag phase KW - Biodegradation KW - Vero cells KW - Transmission electron microscopy KW - Morphogenesis KW - Replicative form KW - Cell culture KW - proteomes KW - stationary phase KW - Coxiella burnetii KW - Differentiation KW - Growth curves KW - Morphology KW - Polymerase chain reaction KW - J 02721:Cell cycle, morphology and motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18063158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Temporal+Analysis+of+Coxiella+burnetii+Morphological+Differentiation&rft.au=Coleman%2C+Sherry+A%3BFischer%2C+Elizabeth+R%3BHowe%2C+Dale%3BMead%2C+David+J%3BHeinzen%2C+Robert+A&rft.aulast=Coleman&rft.aufirst=Sherry&rft.date=2004-11-01&rft.volume=186&rft.issue=21&rft.spage=7344&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Lag phase; Biodegradation; Vero cells; Transmission electron microscopy; Morphogenesis; Replicative form; Cell culture; stationary phase; proteomes; Differentiation; Growth curves; Morphology; Polymerase chain reaction; Coxiella burnetii ER - TY - JOUR T1 - Toxicology and carcinogenesis studies of dipropylene glycol in rats and mice AN - 18055751; 6033875 AB - Dipropylene glycol (DPG) is a component of many commercial products such as antifreeze, air fresheners, cosmetic products, solvents, and plastics. Male and female F344/N rats and B6C3F sub(1) mice were exposed to DPG in the drinking water for 2 weeks, 3 months, or 2 years. In the 2-week and 3-month studies, rats and mice were exposed to 0, 5000, 10, 000, 20, 000, 40, 000, or 80, 000 ppm DPG. There was no mortality in the 2-week studies. In the 3-month rat study, all animals survived to the end of the study. Liver weights of rats exposed to 10, 000 ppm or greater and kidney weights of rats exposed to 40, 000 and 80, 000 ppm were greater than those of the controls. The incidences of liver and kidney lesions were significantly increased in males exposed to 20, 000 ppm or greater and females exposed to 80, 000 ppm. Focal olfactory epithelial degeneration was present in all rats exposed to 80, 000 ppm. In males, the incidences of testicular atrophy, epididymal hypospermia, and preputial gland atrophy were significantly increased in the 80, 000 ppm group. In the 3-month mouse study, three males and one female exposed to 80, 000 ppm died. Liver weights were increased, as was the incidence of centrilobular hypertrophy in males exposed to 40, 000 ppm and males and females exposed to 80, 000 ppm. In the 2-year studies, exposure groups were 0, 2500 (rats only), 10, 000, 20, 000 (mice only) or 40, 000 ppm DPG. Survival of male rats exposed to 40, 000 ppm and mean body weights of males and females exposed to 40, 000 ppm were significantly less than controls. In male rats, exposure to DPG resulted in increased incidences and severities of nephropathy and secondary lesions in the parathyroid and forestomach. Increased incidences of focal histiocytic and focal granulomatous inflammation of the liver were also observed. In male and female rats, there were increased incidences of bile duct hyperplasia and changes in the olfactory epithelium of the nose. In mice, survival of males and females was similar to controls. Mean body weights and water consumption of males exposed to 40, 000 ppm were less than that of the controls. Treatment-related nonneoplastic lesions did not occur in mice. Treatment-related neoplastic lesions did not occur in rats or mice. JF - Toxicology AU - Hooth, MJ AU - Herbert, R A AU - Haseman, J K AU - Orzech, D P AU - Johnson, J D AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Mail Drop EC-35, 79 TW Alexander Drive, Research Triangle Park, NC 27709, USA, hooth@niehs.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 123 EP - 140 PB - Elsevier Science Ireland Ltd., P.O. Box 85 Limerick Ireland VL - 204 IS - 2-3 SN - 0300-483X, 0300-483X KW - mice KW - Toxicology Abstracts KW - Mortality KW - Bile duct KW - Antifreezes KW - Inflammation KW - Preputial gland KW - Hyperplasia KW - Hypertrophy KW - Body weight KW - Carcinogenesis KW - Nephropathy KW - Kidney KW - Liver KW - Degeneration KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18055751?accountid=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=Toxicology+and+carcinogenesis+studies+of+dipropylene+glycol+in+rats+and+mice&rft.au=Hooth%2C+MJ%3BHerbert%2C+R+A%3BHaseman%2C+J+K%3BOrzech%2C+D+P%3BJohnson%2C+J+D%3BBucher%2C+J+R&rft.aulast=Hooth&rft.aufirst=MJ&rft.date=2004-11-01&rft.volume=204&rft.issue=2-3&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/10.1016%2Fj.tox.2004.06.019 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Liver; Body weight; Kidney; Bile duct; Inflammation; Antifreezes; Degeneration; Hypertrophy; Nephropathy; Mortality; Preputial gland; Hyperplasia; Carcinogenesis DO - http://dx.doi.org/10.1016/j.tox.2004.06.019 ER - TY - JOUR T1 - Racial and Ethnic Differences in the Seroprevalence of 6 Infectious Diseases in the United States: Data From NHANES III, 1988-1994 AN - 18030359; 6076151 AB - OBJECTIVES: We examined racial/ethnic differences in the seroprevalence of selected infectious agents in analyses stratified according to risk categories to identify patterns and to determine whether demographic, socioeconomic, and behavioral characteristics explain these differences. METHODS: We analyzed data from the third National Health and Nutrition Examination Survey, comparing differences among groups in regard to the prevalence of infection with hepatitis A, B, and C viruses, Toxoplasma gondii, Helicobacter pylori, and herpes simplex virus type 2. RESULTS: Racial/ethnic differences were greater among those in the low-risk category. In the case of most infectious agents, odds associated with race/ethnicity were almost 2 times greater in that category than in the high- risk category. CONCLUSIONS: Stratification and adjustment for socioeconomic factors reduced or eliminated racial/ethnic differences in the prevalence of infection in the high-risk but not the low-risk group, wherein race/ethnicity remained significant and might have been a surrogate for unmeasured risk factors. JF - American Journal of Public Health AU - Mcquillan, Geraldine M AU - Kruszon-Moran, Deanna AU - Kottiri, Benny J AU - Curtin, Lester R AU - Lucas, Jacqueline W AU - Kington, Raynard S AD - Geraldine M. McQuillan, Deanna Kruszon-Moran, Benny J. Kottiri, and Lester R. Curtin are with the Division of Health Examination Surveys, and Jacqueline B. Lucas is with the Division of Health Interview Statistics, National Center for Health Statistics, Hyattsville, Md. Raynard S. Kington is with the National Institutes of Health, Bethesda, Md. Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 1952 EP - 1958 PB - American Public Health Association, 1015 15th St., N.W. Washington DC 20005 USA VL - 94 IS - 11 SN - 0090-0036, 0090-0036 KW - HSV KW - Risk Abstracts; Health & Safety Science Abstracts KW - Helicobacter pylori KW - Hepatitis A virus KW - Socioeconomics KW - hepatitis A KW - infectious diseases KW - Hepatitis B KW - Hepatitis C KW - Herpes simplex virus KW - Ethnic groups KW - Hepatitis B virus KW - Behavior KW - Hepatitis C virus KW - Toxoplasma gondii 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/18030359?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Public+Health&rft.atitle=Racial+and+Ethnic+Differences+in+the+Seroprevalence+of+6+Infectious+Diseases+in+the+United+States%3A+Data+From+NHANES+III%2C+1988-1994&rft.au=Mcquillan%2C+Geraldine+M%3BKruszon-Moran%2C+Deanna%3BKottiri%2C+Benny+J%3BCurtin%2C+Lester+R%3BLucas%2C+Jacqueline+W%3BKington%2C+Raynard+S&rft.aulast=Mcquillan&rft.aufirst=Geraldine&rft.date=2004-11-01&rft.volume=94&rft.issue=11&rft.spage=1952&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Public+Health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Herpes simplex virus; Toxoplasma gondii; Hepatitis A virus; Hepatitis B virus; Hepatitis C virus; Helicobacter pylori; Socioeconomics; Behavior; Hepatitis B; Hepatitis C; hepatitis A; Ethnic groups; infectious diseases ER - TY - JOUR T1 - Cancer Risks among Radiologists and Radiologic Technologists: Review of Epidemiologic Studies AN - 17884430; 6079726 AB - Radiologists and radiologic technologists were among the earliest occupational groups exposed to ionizing radiation and represent a large segment of the working population exposed to radiation from human-made sources. The authors reviewed epidemiologic data on cancer risks from eight cohorts of over 270 000 radiologists and technologists in various countries. The most consistent finding was increased mortality due to leukemia among early workers employed before 1950, when radiation exposures were high. This, together with an increasing risk of leukemia with increasing duration of work in the early years, provided evidence of an excess risk of leukemia associated with occupational radiation exposure in that period. While findings on several types of solid cancers were less consistent, several studies provided evidence of a radiation effect for breast cancer and skin cancer. To date, there is no clear evidence of an increased cancer risk in medical radiation workers exposed to current levels of radiation doses. However, given a relatively short period of time for which the most recent workers have been followed up and in view of the increasing uses of radiation in modern medical practices, it is important to continue to monitor the health status of medical radiation workers. RSNA, 2004 JF - Radiology AU - Yoshinaga, Shinji AU - Mabuchi, Kiyohiko AU - Sigurdson, Alice J AU - Doody, Michele Morin AU - Ron, Elaine AD - Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Md (S.Y., K.M., A.J.S., M.M.D., E.R.) Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 313 EP - 321 PB - Radiological Society of North America, 820 Jorie Blvd. Oak Brook Illinois 60523-2251 USA VL - 233 IS - 2 SN - 0033-8419, 0033-8419 KW - Health & Safety Science Abstracts; Risk Abstracts KW - Leukemia KW - Occupational exposure KW - Mortality KW - Skin KW - Cancer KW - Reviews KW - Ionizing radiation KW - Breast cancer KW - R2 23080:Industrial and labor KW - H 8000:Radiation Safety/Electrical Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17884430?accountid=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=Radiology&rft.atitle=Cancer+Risks+among+Radiologists+and+Radiologic+Technologists%3A+Review+of+Epidemiologic+Studies&rft.au=Yoshinaga%2C+Shinji%3BMabuchi%2C+Kiyohiko%3BSigurdson%2C+Alice+J%3BDoody%2C+Michele+Morin%3BRon%2C+Elaine&rft.aulast=Yoshinaga&rft.aufirst=Shinji&rft.date=2004-11-01&rft.volume=233&rft.issue=2&rft.spage=313&rft.isbn=&rft.btitle=&rft.title=Radiology&rft.issn=00338419&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 - Ionizing radiation; Cancer; Occupational exposure; Leukemia; Reviews; Skin; Mortality; Breast cancer ER - TY - JOUR T1 - Vaccination by Genetically Modified Dendritic Cells Expressing a Truncated neu Oncogene Prevents Development of Breast Cancer in Transgenic Mice AN - 17855543; 6077500 AB - Dendritic cells (DCs) are powerful antigen-presenting cells that process antigens and present peptide epitopes in the context of the major histocompatibility complex molecules to generate immune responses. DCs are being studied as potential anticancer vaccines because of their ability to present antigens to naive T cells and to stimulate the expansion of antigen-specific T- cell populations. We investigated an antitumor vaccination using DCs modified by transfer of a nonsignaling neu oncogene, a homologue of human HER-2/neu, in a transgenic model of breast cancer. BALB-neuT mice develop breast cancers as a consequence of mammary gland-specific expression of an activated neu oncogene. We vaccinated BALB-neuT mice with bone marrow-derived DCs transduced with Ad.Neu, a recombinant adenovirus expressing a truncated neu oncoprotein. The vaccine stimulated the production of specific anti-neu antibodies, enhanced interferon- gamma expression by T cells, and prevented or delayed the onset of mammary carcinomas in the mice. Over 65% of vaccinated mice remained tumor free at 28 weeks of age, whereas all of the mice in the control groups developed tumors. When challenged with a neu-expressing breast cancer cell line, vaccinated tumor-free animals had delayed tumor growth compared with controls. The antitumor effect of the vaccine was specific for expression of neu. Studies showed that CD4+ T cells were required in order to generate antitumor immunity. Importantly, the effectiveness of the vaccine was not diminished by preexisting immunity to adenovirus, whereas the protection afforded by vaccination that used direct injection of Ad.Neu was markedly reduced in mice with anti-adenovirus antibody titers. DCs modified by recombinant adenoviruses expressing tumor- associated antigens may provide an effective antitumor vaccination strategy. JF - Cancer Research AU - Sakai, Yoshio AU - Morrison, Brian J AU - Burke, JDouglas AU - Park, Jong-Myun AU - Terabe, Masaki AU - Janik, John E AU - Forni, Guido AU - Berzofsky, Jay A AU - Morris, John C AD - Cancer Gene Therapy Section, Metabolism Branch, Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, and Clinical Trials, Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland Y1 - 2004/11/01/ PY - 2004 DA - 2004 Nov 01 SP - 8022 EP - 8028 PB - American Association for Cancer Research, 615 Chestnut St., 17th Floor Philadelphia PA 19106-4404 USA, [URL:http://www.aacr.org/] VL - 64 IS - 21 SN - 0008-5472, 0008-5472 KW - mice KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Oncogenes & Growth Factors Abstracts KW - Major histocompatibility complex KW - Dendritic cells KW - HER2 protein KW - CD4 antigen KW - Oncogenes KW - Neu protein KW - Lymphocytes T KW - Antigen-presenting cells KW - Adenovirus KW - Neu gene KW - Vaccination KW - Antibodies KW - ^g-Interferon KW - Breast cancer KW - B 26020:EGF & EGF receptor family/TGF alpha /Her/ErbB-2 (Neu)/ErbB-3/ErbB-4/amphiregulin KW - W3 33350:Cancer vaccines KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17855543?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Vaccination+by+Genetically+Modified+Dendritic+Cells+Expressing+a+Truncated+neu+Oncogene+Prevents+Development+of+Breast+Cancer+in+Transgenic+Mice&rft.au=Sakai%2C+Yoshio%3BMorrison%2C+Brian+J%3BBurke%2C+JDouglas%3BPark%2C+Jong-Myun%3BTerabe%2C+Masaki%3BJanik%2C+John+E%3BForni%2C+Guido%3BBerzofsky%2C+Jay+A%3BMorris%2C+John+C&rft.aulast=Sakai&rft.aufirst=Yoshio&rft.date=2004-11-01&rft.volume=64&rft.issue=21&rft.spage=8022&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 - Adenovirus; Dendritic cells; Antigen-presenting cells; Breast cancer; Vaccination; Neu gene; Oncogenes; Neu protein; Lymphocytes T; Antibodies; CD4 antigen; HER2 protein; ^g-Interferon; Major histocompatibility complex ER - TY - JOUR T1 - A geometric approach to determine association and coherence of the activation times of cell-cycling genes under differing experimental conditions AN - 17854074; 6076872 AB - Differing arresting agents and protocols can be used to synchronize cells in cultures to specific phases of the cell when studying cell-cycle gene expressions. Often, data derived from individual experiments are analyzed separately, since no appropriate statistical methodology is available at the moment to analyze the data from all such experiments simultaneously. The focus of this paper is to determine the association and coherence of the relative activation times of cell-cycling genes under different experimental conditions. Using a circular-circular regression model, we define two parameters, a rotation parameter for the angular difference between cells' arresting times (phases) in two cell-cycle experiments, and an association parameter to describe the correspondence between the cycle times of maximal expression (phase angles) for a set of genes studied in two experiments. Further, we propose a procedure to assess coherence across multiple experiments, i.e. to what extent the circular ordering of the phase angles of genes is maintained across multiple experiments. Coherence of genes across experiments suggests that functionally these genes tend to respond in a stereotypically sequenced way under different experimental conditions. Our proposed methodology is illustrated by applying it to a HeLa cell-cycle gene-expression data. JF - Bioinformatics AU - Liu, Delong AU - Weinberg, Clarice R AU - Peddada, Shyamal D AD - Biostatistics Branch, MD:A3-03, National Institute of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC Y1 - 2004/11/01/ PY - 2004 DA - 2004 Nov 01 SP - 2521 EP - 2528 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 20 IS - 16 SN - 1367-4803, 1367-4803 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Genetics Abstracts KW - Gene expression KW - Statistics KW - Data processing KW - Cell culture KW - Bioinformatics KW - W 30965:Miscellaneous, Reviews KW - W4 320:Cell Culture & Batch Fermentation KW - G 07300:Theoretical genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17854074?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+geometric+approach+to+determine+association+and+coherence+of+the+activation+times+of+cell-cycling+genes+under+differing+experimental+conditions&rft.au=Liu%2C+Delong%3BWeinberg%2C+Clarice+R%3BPeddada%2C+Shyamal+D&rft.aulast=Liu&rft.aufirst=Delong&rft.date=2004-11-01&rft.volume=20&rft.issue=16&rft.spage=2521&rft.isbn=&rft.btitle=&rft.title=Bioinformatics&rft.issn=13674803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene expression; Cell culture; Data processing; Statistics; Bioinformatics ER - TY - JOUR T1 - The TAO-Gen Algorithm for Identifying Gene Interaction Networks with Application to SOS Repair in E. coli AN - 17853428; 6130403 AB - One major unresolved issue in the analysis of gene expression data is the identification and quantification of gene regulatory networks. Several methods have been proposed for identifying gene regulatory networks, but these methods predominantly focus on the use of multiple pairwise comparisons to identify the network structure. In this article, we describe a method for analyzing gene expression data to determine a regulatory structure consistent with an observed set of expression profiles. Unlike other methods this method goes beyond pairwise evaluations by using likelihood-based statistical methods to obtain the network that is most consistent with the complete data set. The proposed algorithm performs accurately for moderate-sized networks with most errors being minor additions of linkages. However, the analysis also indicates that sample sizes may need to be increased to uniquely identify even moderate-sized networks. The method is used to evaluate interactions between genes in the SOS signaling pathway in Escherichia coli using gene expression data where each gene in the network is over-expressed using plasmids inserts. JF - Environmental Health Perspectives AU - Yamanaka, Takeharu AU - Toyoshiba, Hiroyoshi AU - Sone, H AU - Parham, F M AU - Portier, C J AD - Laboratory of Computational Biology and Risk Analysis, NIEHS, P.O. Box 12233, MD A3-06, 111 Alexander Dr., Research Triangle Park, NC 27709, USA, portier@niehs.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 1614 EP - 1621 VL - 112 IS - 16 SN - 0091-6765, 0091-6765 KW - Microbiology Abstracts B: Bacteriology KW - Gene expression KW - Data processing KW - Statistics KW - Escherichia coli KW - Algorithms KW - Plasmids KW - SOS repair KW - Signal transduction KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17853428?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=The+TAO-Gen+Algorithm+for+Identifying+Gene+Interaction+Networks+with+Application+to+SOS+Repair+in+E.+coli&rft.au=Yamanaka%2C+Takeharu%3BToyoshiba%2C+Hiroyoshi%3BSone%2C+H%3BParham%2C+F+M%3BPortier%2C+C+J&rft.aulast=Yamanaka&rft.aufirst=Takeharu&rft.date=2004-11-01&rft.volume=112&rft.issue=16&rft.spage=1614&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/10.1289%2Ftxg.7105 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Gene expression; Statistics; Data processing; Algorithms; Plasmids; SOS repair; Signal transduction; Escherichia coli DO - http://dx.doi.org/10.1289/txg.7105 ER - TY - JOUR T1 - Identification of oxidized mitochondrial proteins in alcohol-exposed human hepatoma cells and mouse liver AN - 17833387; 6074202 AB - Heavy alcohol consumption can damage various cells and organs partly through production of reactive oxygen species (ROS) and mitochondrial dysfunction. Treatment with antioxidants can significantly reduce the degree of damage. Despite well established roles of ROS in alcohol-induced cell injury, the proteins that are selectively oxidized by ROS are poorly characterized. We hypothesized that certain cysteinyl residues of target proteins are oxidized by ROS upon alcohol exposure, and these modified proteins may play roles in mitochondrial dysfunction. A targeted proteomics approach utilizing biotin-N- maleimide (biotin-NM) as a specific probe to label oxidized cysteinyl residues was employed to investigate which mitochondrial proteins are modified during and after alcohol exposure. Human hepatoma HepG2 cells with transduced CYP2E1 (E47 cells) were used as a model to generate ROS through CYP2E1-mediated ethanol metabolism. Following exposure to 100 mM ethanol for 4 and 8 h, the biotin-NM- labeled oxidized proteins were purified with agarose coupled to either streptavidin or monoclonal antibody against biotin. The purified proteins were resolved by two-dimensional gel electrophoresis and protein spots that displayed differential abundances were excised from the gel, in-gel digested with trypsin and analyzed for identity utilizing either matrix-assisted laser desorption-time of flight mass spectrometry or microcapillary reversed-phase liquid chromatography-tandem mass spectrometry. The results demonstrate that heat shock protein 60, protein disulfide isomerase, mitochondrial aldehyde dehydrogenases, prohibitin, and other proteins were oxidized after alcohol exposure. The identity of some of the proteins purified with streptavidin-agarose was also confirmed by immunoblot analyses using the specific antibody to each target protein. This method was also used to identify oxidized mitochondrial proteins in the alcohol-fed mouse liver. These results suggest that exposure to ethanol causes oxidation of various mitochondrial proteins that may negatively affect their function and contribute to alcohol-induced mitochondrial dysfunction and cellular injury. JF - Proteomics AU - Suh, Soo-Kyung AU - Hood, Brian L AU - Kim, Bong-Jo AU - Conrads, Thomas P AU - Veenstra, Timothy D AU - Song, Byoung J AD - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA, bjs@mail.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 3401 EP - 3412 PB - Wiley-VCH, Postfach 101161 Weinheim 69451 Germany, [mailto:info@wiley-vch.de], [URL:http://www.wiley-vch.de/publish/en/] VL - 4 IS - 11 SN - 1615-9853, 1615-9853 KW - Toxicology Abstracts KW - Heat shock proteins KW - Antioxidants KW - Monoclonal antibodies KW - Hepatocytes KW - Mitochondria KW - Hepatoma KW - Reactive oxygen species KW - Liver KW - proteomics KW - Aldehydes KW - streptavidin KW - Ethanol KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17833387?accountid=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=Proteomics&rft.atitle=Identification+of+oxidized+mitochondrial+proteins+in+alcohol-exposed+human+hepatoma+cells+and+mouse+liver&rft.au=Suh%2C+Soo-Kyung%3BHood%2C+Brian+L%3BKim%2C+Bong-Jo%3BConrads%2C+Thomas+P%3BVeenstra%2C+Timothy+D%3BSong%2C+Byoung+J&rft.aulast=Suh&rft.aufirst=Soo-Kyung&rft.date=2004-11-01&rft.volume=4&rft.issue=11&rft.spage=3401&rft.isbn=&rft.btitle=&rft.title=Proteomics&rft.issn=16159853&rft_id=info:doi/10.1002%2Fpmic.200400971 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mitochondria; Ethanol; proteomics; Hepatoma; Reactive oxygen species; Aldehydes; streptavidin; Hepatocytes; Monoclonal antibodies; Antioxidants; Heat shock proteins; Liver DO - http://dx.doi.org/10.1002/pmic.200400971 ER - TY - JOUR T1 - The effects of antioxidants on radiation-induced apoptosis pathways in TK6 cells AN - 17820377; 6047003 AB - This study was designed to determine if radiation-mediated activation of the apoptotic pathways would be influenced by antioxidants and if a correlation would be found between radioprotection and changes in transduction pathways. Human lymphoblastoid TK6 cells, known to undergo apoptosis as a result of radiation, were irradiated (6 Gy) with and without antioxidants, and then whole- cell lysates were collected. Parallel studies were conducted to assess the survival (clonogenic assay) and apoptotic index. The impacts of two nitroxide antioxidants, tempol and CAT-1, differing in cell permeability, as well as the sulfhydryl antioxidant N-acetyl-L-cysteine (L-NAC), were estimated. Changes in apoptotic pathway proteins and p53 were assessed by Western blotting. Fraction of apoptotic cells was determined by flow cytometry. Tempol (10 mM), which readily enters cells, partially radioprotected TK6 cells against clonogenic killing, but had no effect on radiation-induced apoptotic parameters such as cleaved caspase 3 or cleaved PARP. Tempol alone did not induce cytotoxicity, yet did increase cleaved PARP levels. The radiation-induced increase in p53 protein was partly inhibited by tempol, but was unaffected by CAT-1 and L-NAC. Both CAT-1 (10 mM), which does not enter cells, and L-NAC (10 mM) had no radioprotective effect on cell survival. Although L-NAC did not protect against radiation-induced cytotoxicity, it completely inhibited radiation-induced increase in cleaved caspase 3 and cleaved PARP. Collectively, the results question the validity of using selected apoptosis pathway members as sole indicators of cytotoxicity. JF - Free Radical Biology and Medicine AU - Samuni, A M AU - DeGraff, W AU - Cook, JA AU - Krishna, M C AU - Russo, A AU - Mitchell, J B AD - Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, jbm@helix.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 1648 EP - 1655 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl] VL - 37 IS - 10 SN - 0891-5849, 0891-5849 KW - Toxicology Abstracts KW - Western blotting KW - tempol KW - ^a Radiation KW - Apoptosis KW - Antioxidants KW - p53 protein KW - Flow cytometry KW - N-Acetyl-L-cysteine KW - Poly(ADP-ribose) polymerase KW - Radioprotection KW - Caspase KW - Nitroxide KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17820377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+Radical+Biology+and+Medicine&rft.atitle=The+effects+of+antioxidants+on+radiation-induced+apoptosis+pathways+in+TK6+cells&rft.au=Samuni%2C+A+M%3BDeGraff%2C+W%3BCook%2C+JA%3BKrishna%2C+M+C%3BRusso%2C+A%3BMitchell%2C+J+B&rft.aulast=Samuni&rft.aufirst=A&rft.date=2004-11-01&rft.volume=37&rft.issue=10&rft.spage=1648&rft.isbn=&rft.btitle=&rft.title=Free+Radical+Biology+and+Medicine&rft.issn=08915849&rft_id=info:doi/10.1016%2Fj.freeradbiomed.2004.08.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antioxidants; tempol; Poly(ADP-ribose) polymerase; Apoptosis; p53 protein; Caspase; ^a Radiation; Flow cytometry; Radioprotection; Nitroxide; Western blotting; N-Acetyl-L-cysteine DO - http://dx.doi.org/10.1016/j.freeradbiomed.2004.08.006 ER - TY - JOUR T1 - Comparison of PCR-southern hybridization and quantitative real-time PCR for the detection of JC and BK viral nucleotide sequences in urine and cerebrospinal fluid AN - 17789069; 6143849 AB - The presence of the human polyomaviruses JCV and BKV in immunocompromised patients can lead to lethal diseases and conditions including progressive multifocal leukoencephalopathy (PML), interstitial nephritis, hemorrhagic cystitis, and kidney allograft rejection. Typically, detection of JCV and BKV in clinical samples has employed standard PCR amplification for viral nucleotide sequences, with subsequent confirmation for viral genome specificity of PCR products by southern blot hybridization. Here, we directly tested a validated PCR-southern protocol with a TaqMan real-time PCR protocol (Applied Biosystems) to assay clinical samples of urine and cerebrospinal fluid. We found equal specificity and sensitivity with both methods. However, real-time allowed for absolute viral-genome quantitation without the use of radionucleotides and was performed more rapidly, in as little as 24h. Such advantages are important to consider in the effort to establish international standardization of controls for the detection of JCV and BKV, which would aid in screening confidence and the reliable assessment of anti-viral therapies. JF - Journal of Virological Methods AU - Ryschkewitsch, C AU - Jensen, P AU - Hou, J AU - Fahle, G AU - Fischer, S AU - Major, E O AD - Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 36 Convent Drive, Bethesda, MD 20892-4164, USA, majorg@ninds.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 217 EP - 221 VL - 121 IS - 2 SN - 0166-0934, 0166-0934 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Graft rejection KW - Kidney transplantation KW - Progressive multifocal leukoencephalopathy KW - Standardization KW - Cerebrospinal fluid KW - Antiviral agents KW - Hemorrhagic cystitis KW - Polymerase chain reaction KW - Quantitation KW - JC virus KW - BK virus KW - Urine KW - Nephritis KW - A 01114:Viruses KW - V 22121:Diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17789069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virological+Methods&rft.atitle=Comparison+of+PCR-southern+hybridization+and+quantitative+real-time+PCR+for+the+detection+of+JC+and+BK+viral+nucleotide+sequences+in+urine+and+cerebrospinal+fluid&rft.au=Ryschkewitsch%2C+C%3BJensen%2C+P%3BHou%2C+J%3BFahle%2C+G%3BFischer%2C+S%3BMajor%2C+E+O&rft.aulast=Ryschkewitsch&rft.aufirst=C&rft.date=2004-11-01&rft.volume=121&rft.issue=2&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virological+Methods&rft.issn=01660934&rft_id=info:doi/10.1016%2Fj.jviromet.2004.06.021 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - JC virus; BK virus; Polymerase chain reaction; Urine; Cerebrospinal fluid; Kidney transplantation; Antiviral agents; Progressive multifocal leukoencephalopathy; Hemorrhagic cystitis; Nephritis; Standardization; Graft rejection; Quantitation DO - http://dx.doi.org/10.1016/j.jviromet.2004.06.021 ER - TY - JOUR T1 - Nocardia kruczakiae sp. nov., a Pathogen in Immunocompromised Patients and a Member of the "N. nova Complex" AN - 17759115; 6078738 AB - Molecular methodologies have become useful techniques for the identification of pathogenic Nocardia species and for the recognition of novel species that are capable of causing human disease. Two isolates recovered from immunocompromised patients were characterized as Nocardia nova by biochemical and susceptibility testing results. The restriction fragment length polymorphism (RFLP) patterns obtained by restriction endonuclease analysis (REA) of an amplified portion of the heat shock protein gene were identical to those obtained with the type strain of N. nova. REA of an amplified portion of the 16S rRNA gene showed RFLP patterns that were unlike those obtained for the type strain of N. nova but that were similar to those obtained for the type strains of N. africana and N. veterana. Subsequent sequencing of a portion of the 16S rRNA gene produced identical results for the two patient isolates. Sequence analysis of 1,352-bp portions of the 16S rRNA gene indicated that these isolates were 99.8% similar to the recently described species N. veterana but were only 99.3, 98.1, and 98.1% similar to the type strains of N. africana, N. nova, and N. vaccinii, respectively. DNA-DNA hybridization studies confirmed that the two patient isolates belonged to the same species but were not closely related to N. africana, N. nova, N. vaccinii, or N. veterana. The patient isolates have been designated N. kruczakiae sp. nov. Because N. africana, N. veterana, and the new species are not readily differentiated from N. nova by phenotypic methods alone, the designation "N. nova complex" can be used to designate isolates such as these that phenotypically resemble N. nova but that have not been definitively characterized by 16S rRNA gene sequencing or DNA-DNA hybridization. JF - Journal of Clinical Microbiology AU - Conville, Patricia S AU - Brown, June M AU - Steigerwalt, Arnold G AU - Lee, Judy W AU - Anderson, Victoria L AU - Fishbain, Joel T AU - Holland, Steven M AU - Witebsky, Frank G AD - Microbiology Service, Department of Laboratory Medicine, Warren G. Magnuson Clinical Center. Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland. Meningitis and Special Pathogens Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, Georgia. Walter Reed Army Medical Center, Washington, D.C. Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 5139 EP - 5145 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 42 IS - 11 SN - 0095-1137, 0095-1137 KW - Microbiology Abstracts B: Bacteriology KW - Nocardia veterana KW - Heat shock proteins KW - Nocardia africana KW - Immunocompromised hosts KW - Restriction fragment length polymorphism KW - Nocardia nova KW - Endonuclease KW - Nocardia vaccinia KW - rRNA 16S KW - Nocardia kruczakiae KW - New species KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17759115?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+kruczakiae+sp.+nov.%2C+a+Pathogen+in+Immunocompromised+Patients+and+a+Member+of+the+%22N.+nova+Complex%22&rft.au=Conville%2C+Patricia+S%3BBrown%2C+June+M%3BSteigerwalt%2C+Arnold+G%3BLee%2C+Judy+W%3BAnderson%2C+Victoria+L%3BFishbain%2C+Joel+T%3BHolland%2C+Steven+M%3BWitebsky%2C+Frank+G&rft.aulast=Conville&rft.aufirst=Patricia&rft.date=2004-11-01&rft.volume=42&rft.issue=11&rft.spage=5139&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Nocardia africana; Nocardia vaccinia; Nocardia veterana; Nocardia kruczakiae; Nocardia nova; rRNA 16S; Restriction fragment length polymorphism; Heat shock proteins; Endonuclease; New species; Immunocompromised hosts ER - TY - JOUR T1 - Effect of Dosage on Immunogenicity of a Vi Conjugate Vaccine Injected Twice into 2- to 5-Year-Old Vietnamese Children AN - 17755638; 6062314 AB - In a double-blind, randomized, and placebo-controlled previous trial, the efficacy of Vi-rEPA for typhoid fever in 2- to 5-year-olds was 89.0% for 46 months. Vi-rEPA contained 25 mu g of Vi and induced a greater-than-eightfold rise in immunoglobulin G (IgG) anti-Vi in all of the vaccinees tested. In this investigation, we conducted a dosage-immunogenicity study of 5, 12.5, and 25 mu g of Vi-rEPA in this age group. Two doses of Vi-rEPA were injected 6 weeks apart. Blood samples were taken before and at 10 weeks (4 weeks after the second injection) and 1 year later. All postimmunization geometric mean (GM) levels were higher than the preimmune levels (P 3.52 EU/ml (estimated minimum protective level). One year later, the levels declined about sevenfold (13.3 and 11.3 versus 6.43 EU/ml, P 96% of the children had a greater-than-eightfold rise. This study also confirmed the safety and consistent immunogenicity of the four lots of Vi-rEPA used in this and previous trials. JF - Infection and Immunity AU - Canh, Do Gia AU - Lin, Feng-Ying (Kimi) AU - Thiem, Vu Dinh AU - Trach, Dang Duc AU - Trong, Nguyen Dinh AU - Mao, Nguyen Duc AU - Hunt, Steven AU - Schneerson, Rachel AU - Robbins, John B AU - Chu, Chiayung AU - Shiloach, Joseph AU - Bryla, Dolores A AU - Bonnet, Marie-Claude AU - Schulz, Dominique AU - Szu, Shousun C AD - Diarrhea Diseases Epidemiology and Field Research Section, National Institute of Hygiene & Epidemiology, Hanoi. Centre for Preventive Medicine, Phu Tho Province, Vietnam. National Institute of Child Health and Human Development. National Institute of Digestive, Diabetes, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. Aventis Pasteur, Lyon, France Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 6586 EP - 6588 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 72 IS - 11 SN - 0019-9567, 0019-9567 KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Immunity KW - Children KW - Vietnam KW - Immunogenicity KW - Immunoglobulin G KW - Vaccines KW - Typhoid fever KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17755638?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+Dosage+on+Immunogenicity+of+a+Vi+Conjugate+Vaccine+Injected+Twice+into+2-+to+5-Year-Old+Vietnamese+Children&rft.au=Canh%2C+Do+Gia%3BLin%2C+Feng-Ying+%28Kimi%29%3BThiem%2C+Vu+Dinh%3BTrach%2C+Dang+Duc%3BTrong%2C+Nguyen+Dinh%3BMao%2C+Nguyen+Duc%3BHunt%2C+Steven%3BSchneerson%2C+Rachel%3BRobbins%2C+John+B%3BChu%2C+Chiayung%3BShiloach%2C+Joseph%3BBryla%2C+Dolores+A%3BBonnet%2C+Marie-Claude%3BSchulz%2C+Dominique%3BSzu%2C+Shousun+C&rft.aulast=Canh&rft.aufirst=Do&rft.date=2004-11-01&rft.volume=72&rft.issue=11&rft.spage=6586&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vietnam; Children; Immunoglobulin G; Vaccines; Immunogenicity; Immunity; Typhoid fever ER - TY - JOUR T1 - Comparison of Retroviral Transduction Efficiency in CD34 super(+) Cells Derived from Bone Marrow versus G-CSF-Mobilized or G-CSF Plus Stem Cell Factor-Mobilized Peripheral Blood in Nonhuman Primates AN - 17731276; 6079947 AB - Hematopoietic stem cells (HSCs) are ideal targets for genetic manipulation in the treatment of several congenital and acquired disorders affecting the hematopoietic compartment. Although G-CSF-mobilized peripheral blood CD34 super(+) cells are the favored source of hematopoietic stem cells in clinical transplantation, this source of stem cells does not provide meaningful engraftment levels of genetically modified cells compared with G-CSF + stem cell factor (SCF)-mobilized cells in nonhuman primates. Furthermore, the use of G-CSF mobilization can have disastrous consequences in patients with sickle cell disease, a long-held target disorder for HSC-based gene therapy approaches. We therefore conducted a study to compare the levels of genetically modified cells attainable after retroviral transduction of CD34 super(+) cells collected from a bone marrow (BM) harvest with CD34 super(+) cells collected from a leukapheresis product after mobilization with G-CSF (n = 3) or G-CSF in combination with SCF (n = 3) in the rhesus macaque autologous transplantation model. Transductions were performed using retroviral vector supernatant on fibronectin-coated plates for 96 hours in the presence of stimulatory cytokines. BM was equal to or better than G-CSF-mobilized peripheral blood as a source of HSCs for retroviral transduction. Although the highest marking observed was derived from G-SCF + SCF-mobilized peripheral blood in two animals, marking in the third originated only from the BM fraction. These results demonstrate that steady-state BM is at least equivalent to G-CSF-mobilized peripheral blood as a source of HSCs for retroviral gene transfer and the only currently available source for patients with sickle cell disease. JF - Stem Cells AU - Hematti, Peiman AU - Tuchman, Sascha AU - Larochelle, Andre AU - Metzger, Mark E AU - Donahue, Robert E AU - Tisdale, John F AD - Hematology Branch, NHLBI, National Institutes of Health, and Molecular and Clinical Hematology Branch, NIDDK, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 1062 EP - 1069 VL - 22 IS - 6 SN - 1066-5099, 1066-5099 KW - Primates KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Animal models KW - Bone marrow KW - Granulocyte colony-stimulating factor KW - Stem cells KW - Retrovirus KW - Stem cell factor KW - Allografts KW - Sickle cell disease KW - Autografts KW - Leukapheresis KW - Gene therapy KW - Macaca KW - Peripheral blood KW - CD34 antigen KW - Hemopoiesis KW - Transduction KW - W3 33181:Gene therapy vectors KW - F 06828:Allograft KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - G 07419:Primates (except man) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17731276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Stem+Cells&rft.atitle=Comparison+of+Retroviral+Transduction+Efficiency+in+CD34+super%28%2B%29+Cells+Derived+from+Bone+Marrow+versus+G-CSF-Mobilized+or+G-CSF+Plus+Stem+Cell+Factor-Mobilized+Peripheral+Blood+in+Nonhuman+Primates&rft.au=Hematti%2C+Peiman%3BTuchman%2C+Sascha%3BLarochelle%2C+Andre%3BMetzger%2C+Mark+E%3BDonahue%2C+Robert+E%3BTisdale%2C+John+F&rft.aulast=Hematti&rft.aufirst=Peiman&rft.date=2004-11-01&rft.volume=22&rft.issue=6&rft.spage=1062&rft.isbn=&rft.btitle=&rft.title=Stem+Cells&rft.issn=10665099&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 - Primates; Macaca; Retrovirus; CD34 antigen; Transduction; Stem cell factor; Granulocyte colony-stimulating factor; Bone marrow; Sickle cell disease; Gene therapy; Leukapheresis; Stem cells; Peripheral blood; Hemopoiesis; Allografts; Autografts; Animal models ER - TY - JOUR T1 - Finding time for allosteric interactions AN - 17714020; 6130848 AB - Drug discovery programs generally look for compounds that bind to orthosteric sites--binding sites for the endogenous agonist--on target receptors. However, drug targets often have secondary, allosteric sites, and binding at these sites can affect the affinity of agonists and antagonists at the orthosteric site. Although the importance of allosteric modifiers is increasingly recognized, quantification of allosteric interactions has proven difficult. In this issue, Chen and Hage describe an alternative approach for determining the allosteric interactions of compounds that bind to human serum albumin (HSA). Using bioinformatic chromatography, they show that allosteric interactions can be readily identified and the extent of the interactions between orthosteric and allosteric sites determined. JF - Nature Biotechnology AU - Wainer, Irving W AD - National Institute on Aging, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA, Wainerir@grc.nia.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 1376 EP - 1377 PB - Nature Publishing Group VL - 22 IS - 11 SN - 1087-0156, 1087-0156 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Biopolymers KW - Antagonists KW - Drug discovery KW - Phenytoin KW - Allosteric properties KW - L-Tryptophan KW - Drug interaction KW - Ibuprofen KW - Chromatography KW - human serum albumin KW - Acetic acid KW - Blood KW - Reviews KW - Bioinformatics KW - W4 140:Bioinformatics & Computers in Health & Medicine KW - W3 33080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17714020?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Finding+time+for+allosteric+interactions&rft.au=Wainer%2C+Irving+W&rft.aulast=Wainer&rft.aufirst=Irving&rft.date=2004-11-01&rft.volume=22&rft.issue=11&rft.spage=1376&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2Fnbt1104-1376 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Blood; Acetic acid; Phenytoin; Ibuprofen; Biopolymers; L-Tryptophan; Drug interaction; Allosteric properties; Reviews; Bioinformatics; Drug discovery; Chromatography; human serum albumin; Antagonists DO - http://dx.doi.org/10.1038/nbt1104-1376 ER - TY - JOUR T1 - Commuting Physical Activity and Risk of Colon Cancer in Shanghai, China AN - 17706090; 6061696 AB - Colon cancer incidence rates have been rapidly increasing in Shanghai, China, for reasons still unclear. Low physical activity is a known risk factor for colon cancer. The authors examined the effects of physical activity, particularly commuting physical activity, and its joint effects with body mass index on colon cancer risk in a population-based, case-control study. The study included 931 incident colon cancer patients and 1,552 randomly selected controls in Shanghai between 1990 and 1993. Colon cancer risk was significantly reduced among subjects with high commuting physical activity (odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.27, 0.87 for men; OR = 0.56, 95% CI: 0.21, 0.91 for women), particularly among those who had high commuting physical activity for at least 35 years (OR = 0.34, 95% CI: 0.09, 0.76 for men; OR = 0.31, 95% CI: 0.07, 0.72 for women). Commuting physical activity significantly modified the risk conferred by high body mass index, with the highest risk observed among those at the highest quintile of body mass index and the lowest activity level (OR = 6.43, 95% CI: 1.82, 8.54 for men; OR = 7.42, 95% CI: 2.84, 10.01 for women). Our results suggest that regular and frequent physical activity over a long period of time protects from colon cancer and significantly modifies the body mass index-associated risk. JF - American Journal of Epidemiology AU - Hou, Lifang AU - Ji, Bu-Tian AU - Blair, Aaron AU - Dai, Qi AU - Gao, Yu-Tang AU - Chow, Wong-Ho AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. Y1 - 2004/11/01/ PY - 2004 DA - 2004 Nov 01 SP - 860 EP - 867 PB - Johns Hopkins University, School of Hygiene and Public Health VL - 160 IS - 9 SN - 0002-9262, 0002-9262 KW - commuting KW - colon cancer KW - Physical Education Index; Risk Abstracts KW - Body mass KW - Risk factors KW - China, People's Rep., Shanghai KW - Exercise KW - Adults KW - physical activity KW - Cancer KW - R2 23060:Medical and environmental health KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17706090?accountid=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=Commuting+Physical+Activity+and+Risk+of+Colon+Cancer+in+Shanghai%2C+China&rft.au=Hou%2C+Lifang%3BJi%2C+Bu-Tian%3BBlair%2C+Aaron%3BDai%2C+Qi%3BGao%2C+Yu-Tang%3BChow%2C+Wong-Ho&rft.aulast=Hou&rft.aufirst=Lifang&rft.date=2004-11-01&rft.volume=160&rft.issue=9&rft.spage=860&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - Physical Education Index; ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adults; Exercise; Risk factors; Body mass; Cancer; China, People's Rep., Shanghai; physical activity ER - TY - JOUR T1 - Arsenic Concentrations in Prediagnostic Toenails and the Risk of Bladder Cancer in a Cohort Study of Male Smokers AN - 17702762; 6061695 AB - At high concentrations, inorganic arsenic can cause bladder cancer in humans. However, it is unclear whether low exposure to inorganic arsenic in drinking water (<100 mu g/liter) is related to bladder cancer risk. No study has been known to use biomarkers to assess the relation between individual arsenic exposure and bladder cancer risk. Toenail samples provide an integrated measure of internal arsenic exposure and reflect long-term exposure. The authors examined the relation between toenail arsenic levels and bladder cancer risk among participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a cohort of Finnish male smokers aged 50-69 years. Data for 280 incident bladder cancer cases, identified between baseline (1985-1988) and April 1999, were available for analysis. One control was matched to each case on the basis of age, toenail collection date, intervention group, and smoking duration. Arsenic levels in toenail samples were determined by using neutron activation analysis. Logistic regression analyses were performed to estimate odds ratios. Arsenic toenail concentrations in this Finnish study were similar to those reported in US studies (range: 0.02-17.5 mu g/g). The authors observed no association between inorganic arsenic concentration and bladder cancer risk (odds ratio = 1.13, 95% confidence interval: 0.70, 1.81 for the highest vs. lowest quartile). These findings suggest that low-level arsenic exposure is unlikely to explain a substantial excess risk of bladder cancer. JF - American Journal of Epidemiology AU - Michaud, Dominique S AU - Wright, Margaret E AU - Cantor, Kenneth P AU - Taylor, Philip R AU - Virtamo, Jarmo AU - Albanes, Demetrius AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD. Y1 - 2004/11/01/ PY - 2004 DA - 2004 Nov 01 SP - 853 EP - 859 PB - Johns Hopkins University, School of Hygiene and Public Health VL - 160 IS - 9 SN - 0002-9262, 0002-9262 KW - urinary bladder KW - Risk Abstracts; Health & Safety Science Abstracts; Toxicology Abstracts KW - Heavy metals KW - Smoking KW - Arsenic KW - Urinary bladder KW - males KW - Cancer KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health KW - X 24163:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17702762?accountid=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=Arsenic+Concentrations+in+Prediagnostic+Toenails+and+the+Risk+of+Bladder+Cancer+in+a+Cohort+Study+of+Male+Smokers&rft.au=Michaud%2C+Dominique+S%3BWright%2C+Margaret+E%3BCantor%2C+Kenneth+P%3BTaylor%2C+Philip+R%3BVirtamo%2C+Jarmo%3BAlbanes%2C+Demetrius&rft.aulast=Michaud&rft.aufirst=Dominique&rft.date=2004-11-01&rft.volume=160&rft.issue=9&rft.spage=853&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 - Arsenic; Heavy metals; Cancer; males; Smoking; Urinary bladder ER - TY - JOUR T1 - Pesticides and Lung Cancer Risk in the Agricultural Health Study Cohort AN - 17702410; 6061698 AB - The authors examined the relation between 50 widely used agricultural pesticides and lung cancer incidence in the Agricultural Health Study, a prospective cohort study of 57,284 pesticide applicators and 32,333 spouses of farmer applicators with no prior history of lung cancer. Self-administered questionnaires were completed at enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 2001. A lung cancer standardized incidence ratio of 0.44 (95% confidence interval: 0.39, 0.49) was observed overall, due in large part to a low cigarette smoking prevalence. Two widely used herbicides, metolachlor and pendimethalin (for low-exposed groups to four higher exposure categories: odds ratio (OR) = 1.0, 1.6, 1.2, 5.0; p sub(trend) = 0.0002; and OR = 1.0, 1.6, 2.1, 4.4; p sub(trend) = 0.003, respectively), and two widely used insecticides, chlorpyrifos and diazinon (OR = 1.0, 1.1, 1.7, 1.9; p sub(trend) = 0.03; and OR = 1.0, 1.6, 2.7, 3.7; p sub(trend) = 0.04, respectively), showed some evidence of exposure response for lung cancer. These excesses could not be explained by previously identified lung cancer risk factors. The usage levels in this cohort are considerably higher than those typically experienced by the general population. An excess risk among spouses directly exposed to pesticides could not be evaluated at this time. JF - American Journal of Epidemiology AU - Alavanja, Michael CR AU - Dosemeci, Mustafa AU - Samanic, Claudine AU - Lubin, Jay AU - Lynch, Charles F AU - Knott, Charles AU - Barker, Joseph AU - Hoppin, Jane A AU - Sandler, Dale P AU - Coble, Joseph AU - Thomas, Kent AU - Blair, Aaron AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD. Y1 - 2004/11/01/ PY - 2004 DA - 2004 Nov 01 SP - 876 EP - 885 PB - Johns Hopkins University, School of Hygiene and Public Health VL - 160 IS - 9 SN - 0002-9262, 0002-9262 KW - Health & Safety Science Abstracts; Risk Abstracts; Toxicology Abstracts KW - Historical account KW - Agrochemicals KW - Chlorpyrifos KW - Insecticides KW - Pesticides KW - Cigarette smoking KW - Diazinon KW - Occupational exposure KW - Lung cancer KW - R2 23080:Industrial and labor KW - X 24134:Pathology KW - H 5000:Pesticides UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17702410?accountid=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=Pesticides+and+Lung+Cancer+Risk+in+the+Agricultural+Health+Study+Cohort&rft.au=Alavanja%2C+Michael+CR%3BDosemeci%2C+Mustafa%3BSamanic%2C+Claudine%3BLubin%2C+Jay%3BLynch%2C+Charles+F%3BKnott%2C+Charles%3BBarker%2C+Joseph%3BHoppin%2C+Jane+A%3BSandler%2C+Dale+P%3BCoble%2C+Joseph%3BThomas%2C+Kent%3BBlair%2C+Aaron&rft.aulast=Alavanja&rft.aufirst=Michael&rft.date=2004-11-01&rft.volume=160&rft.issue=9&rft.spage=876&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 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Chlorpyrifos; Insecticides; Cigarette smoking; Pesticides; Agrochemicals; Diazinon; Occupational exposure; Lung cancer; Historical account ER - TY - JOUR T1 - Oral and Dermal Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Induces Cutaneous Papillomas and Squamous Cell Carcinomas in Female Hemizygous Tg.AC Transgenic Mice AN - 17700425; 6080021 AB - Tg.AC mice develop epidermal papillomas in response to treatment with dermally applied nongenotoxic and complete carcinogens. The persistent environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a multi- site rodent carcinogen and tumor promoter that induces the formation of papillomas in Tg.AC mice. To examine the dose-response relationship and compare dermal and oral routes of exposure for TCDD-induced skin papillomas, female Tg.AC mice were exposed dermally to average daily doses of 0, 2.1, 7.3, 15, 33, 52, 71, 152, and 326 ng TCDD/kg/day or 0, 75, 321, and 893 ng TCDD/kg body weight by gavage for 26 weeks. The incidence of cutaneous papillomas was increased in a dose-dependent manner, and tumors developed earlier with higher exposure to TCDD regardless of route of administration. Increased incidences of cutaneous squamous cell carcinomas were observed in mice exposed to dermal (=>52 ng/kg) and oral (893 ng/kg) TCDD. Higher gavage doses than dermal exposure doses were required to induce papillomas and squamous cell carcinomas. Despite a linear correlation between administered dose and terminal skin concentrations, the incidence of tumor formation was lower in the gavage study than in the dermal study with respect to mean terminal skin TCDD concentrations. These studies demonstrate that, although Tg.AC mice are less responsive to TCDD by gavage than by dermal exposure, the induction of skin neoplasms is a response to systemic exposure and not solely a local response at the site of dermal application. Differences in response between the routes of exposure may reflect pharmacokinetic differences in the delivery of TCDD to the skin over the duration of the study. JF - Toxicological Sciences AU - Wyde, Michael E AU - Braen, Angelique PJM AU - Hejtmancik, Milton AU - Johnson, Jerry D AU - Toft, John D AU - Blake, James C AU - Cooper, Stephen D AU - Mahler, Joel AU - Vallant, Molly AU - Bucher, John R AU - Walker, Nigel J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 34 EP - 45 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 82 IS - 1 SN - 1096-6080, 1096-6080 KW - Toxicology Abstracts KW - Body weight KW - Skin cancer KW - TCDD KW - squamous cell carcinoma KW - Carcinogens KW - Contaminants KW - Transgenic mice KW - Pharmacokinetics KW - X 24222:Analytical procedures UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17700425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Oral+and+Dermal+Exposure+to+2%2C3%2C7%2C8-Tetrachlorodibenzo-p-Dioxin+%28TCDD%29+Induces+Cutaneous+Papillomas+and+Squamous+Cell+Carcinomas+in+Female+Hemizygous+Tg.AC+Transgenic+Mice&rft.au=Wyde%2C+Michael+E%3BBraen%2C+Angelique+PJM%3BHejtmancik%2C+Milton%3BJohnson%2C+Jerry+D%3BToft%2C+John+D%3BBlake%2C+James+C%3BCooper%2C+Stephen+D%3BMahler%2C+Joel%3BVallant%2C+Molly%3BBucher%2C+John+R%3BWalker%2C+Nigel+J&rft.aulast=Wyde&rft.aufirst=Michael&rft.date=2004-11-01&rft.volume=82&rft.issue=1&rft.spage=34&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - TCDD; Skin cancer; squamous cell carcinoma; Carcinogens; Body weight; Transgenic mice; Pharmacokinetics; Contaminants ER - TY - JOUR T1 - Origin pairing ('handcuffing') and unpairing in the control of P1 plasmid replication AN - 17489117; 6225319 AB - The P1 plasmid origin has an array of five binding sites (iterons) for the plasmid-encoded initiator protein RepA. Saturation of these sites is required for initiation. Iterons can also pair via their bound RepAs. The reaction, called handcuffing, is believed to be the key to control initiation negatively. Here we have determined some of the mechanistic details of the reaction. We show that handcuffed RepA-iteron complexes dissociate when they are diluted or challenged with cold competitor iterons, suggesting spontaneous reversibility of the handcuffing reaction. The complex formation increases with increased RepA binding, but decreases upon saturation of binding. Complex formation also decreases in the presence of molecular chaperones (DnaK and DnaJ) that convert RepA dimers to monomers. This indicates that dimers participate in handcuffing, and that chaperones are involved in reversing handcuffing. They could play a direct role by reducing dimers and an indirect role by increasing monomers that would compete out the weaker binding dimers from the origin. We propose that an increased monomer to dimer ratio is the key to reverse handcuffing. JF - Molecular Microbiology AU - Das, Nilangshu AU - Chattoraj, Dhruba K AD - Laboratory of Biochemistry, CCR, NCI, NIH, Bethesda, MD 20892-4255, USA, chattord@mail.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 836 EP - 849 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 54 IS - 3 SN - 0950-382X, 0950-382X KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Replication KW - DnaJ protein KW - repA gene KW - Plasmids KW - Monomers KW - Replication initiation KW - Replication origins KW - DnaK protein KW - Chaperones KW - J 02760:Plasmids KW - N 14030:DNA: biosynthesis, repair & replication cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17489117?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Origin+pairing+%28%27handcuffing%27%29+and+unpairing+in+the+control+of+P1+plasmid+replication&rft.au=Das%2C+Nilangshu%3BChattoraj%2C+Dhruba+K&rft.aulast=Das&rft.aufirst=Nilangshu&rft.date=2004-11-01&rft.volume=54&rft.issue=3&rft.spage=836&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04322.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Figures, 8; references, 45. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Monomers; Chaperones; repA gene; DnaJ protein; DnaK protein; Plasmids; Replication origins; Replication; Replication initiation DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04322.x ER - TY - JOUR T1 - Axiom of determining transcription start points by RNA polymerase in Escherichia coli AN - 17487334; 6225308 AB - To investigate the determining factors in the selection of the transcription start points (tsp) by RNA polymerase of Escherichia coli, we systematically deleted or substituted single base pairs (bps) at 25 putative critical positions in the two extended -10 promoters, P1 and P2, of the gal operon. These changes extend downstream from -24 to +1 of the P1 promoter. In vitro transcription assays using supercoiled DNA templates revealed a preference for a purine in the non-template strand for tsp in both promoters. The optimal tsp is the 11th bp counting downstream from the -10 position. A single bp deletion anywhere from -10 to +1 switched the tsp to the next available purine 2-3 bp downstream on the non-template strand whereas deleting a single bp at position from -24 to -11 did not affect the tsp. The nature of the 10 bp sequence of the -10 to -1 region, while affecting promoter strength, did not influence tsp. The cAMP-CRP complex, which stimulates P1 and represses P2, did not affect the tsp selection process. The rules of tsp selection by RNA polymerase containing sigma super(70) in gal and pyr promoters discussed here may be applicable to others. JF - Molecular Microbiology AU - Lewis, Dale EA AU - Adhya, Sankar AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA, sadhya@helix.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 692 EP - 701 PB - Blackwell Publishing Ltd., 9600 Garsington Road Oxford OX4 2DQ UK, [URL:http://www.blackwellpublishing.com] VL - 54 IS - 3 SN - 0950-382X, 0950-382X KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Deletion KW - Transcription KW - Enumeration KW - purines KW - Transcription initiation KW - Promoters KW - DNA-directed RNA polymerase KW - DNA KW - Escherichia coli KW - Galactose operon KW - Base pairs KW - J 02726:RNA and ribosomes KW - N 14010:Physical & Computer Methods & Assays UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17487334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Axiom+of+determining+transcription+start+points+by+RNA+polymerase+in+Escherichia+coli&rft.au=Lewis%2C+Dale+EA%3BAdhya%2C+Sankar&rft.aulast=Lewis&rft.aufirst=Dale&rft.date=2004-11-01&rft.volume=54&rft.issue=3&rft.spage=692&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/10.1111%2Fj.1365-2958.2004.04318.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Figures, 7; tables, 1; references, 32. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Promoters; Transcription initiation; DNA-directed RNA polymerase; purines; Deletion; Galactose operon; Enumeration; Transcription; DNA; Base pairs DO - http://dx.doi.org/10.1111/j.1365-2958.2004.04318.x ER - TY - JOUR T1 - "Squashing peanuts and smashing pumpkins": How noise distorts diffusion-weighted MR data AN - 17394397; 6495614 AB - New diffusion-weighted imaging (DWI) methods, including high-b, q-space, and high angular resolution MRI methods, attempt to extract information about non-Gaussian diffusion in tissue that is not provided by low-b-value (b approximately 1000 s/mm super(2)) diffusion or diffusion tensor magnetic resonance imaging (DT-MRI). Additionally, DWI data with higher spatial resolution are being acquired to resolve fine anatomic structures, such as white matter fasciculi. Increasing diffusion-weighting or decreasing voxel size can reduce the signal-to-noise ratio so that some DWI signals are close to the background noise level. Here we report several new artifacts that can be explained by considering how background noise affects the peanut-shaped angular apparent diffusion coefficient (ADC) profile. These include an orientationally dependent deviation from Gaussian behavior of the ADC profile, an underestimation of indices of diffusion anisotropy, and a correlation between estimates of mean diffusivity and diffusion anisotropy. We also discuss how noise can cause increased gray/white matter DWI contrast at higher b values and an apparent elevation of diffusion anisotropy in acute ischemia. Importantly, all of these artifacts are negligible in the b-value range typically used in DT-MRI of brain (b approximately 1000 s/mm super(2)). Finally, we demonstrate a strategy for ameliorating the rectified noise artifact in data collected at higher b values. JF - Magnetic Resonance in Medicine AU - Jones, Derek K AU - Basser, Peter J AD - National Institutes of Health, Building 13, Room 3W16E, 13 South Drive, Bethesda, MD 20892-5772 USA, jonesde@mail.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 979 EP - 993 PB - John Wiley & Sons, Ltd. VL - 52 IS - 5 SN - 0740-3194, 0740-3194 KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - Neuroimaging KW - Anisotropy KW - Information processing KW - Magnetic resonance imaging KW - Brain KW - Substantia alba KW - Diffusion KW - N.M.R. KW - Ischemia KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17394397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=%22Squashing+peanuts+and+smashing+pumpkins%22%3A+How+noise+distorts+diffusion-weighted+MR+data&rft.au=Jones%2C+Derek+K%3BBasser%2C+Peter+J&rft.aulast=Jones&rft.aufirst=Derek&rft.date=2004-11-01&rft.volume=52&rft.issue=5&rft.spage=979&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20283 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-05-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Neuroimaging; Anisotropy; Information processing; Magnetic resonance imaging; Brain; Substantia alba; N.M.R.; Diffusion; Ischemia DO - http://dx.doi.org/10.1002/mrm.20283 ER - TY - JOUR T1 - Respiratory and general health impairments of ragpickers in India: a study in Delhi AN - 17359547; 6436986 AB - Objective: This study attempted to assess the respiratory and general health of ragpickers who rummage through the garbage dumps and landfill sites in India to collect and sell recyclable materials for a living. Methods: 98 ragpickers and 60 controls from Delhi, matched for age, sex, and socioeconomic conditions, were examined. Health data were obtained from questionnaire survey, clinical examination, and laboratory investigations. Lung function was evaluated by spirometry. Results: After controlling for smoking as a confounder, respiratory symptoms and lung function decrement were recorded in 94% and 52% of the ragpickers, respectively, compared with 56% and 34% of controls. The ragpickers showed a higher prevalence of low hemoglobin, high circulating eosinophil and monocyte counts, unhealthy gums, frequent diarrhea, and dermatitis, when compared with controls. Their sputum showed an abundance of alveolar macrophages, siderophages and inflammatory cells, and a very high frequency of squamous metaplasia and dysplasia of bronchial epithelial cells, suggesting inflammation and cellular changes in the airways. Conclusion: The ragpickers suffer from a multitude of health problems which seem related to their occupation. JF - International Archives of Occupational and Environmental Health AU - Ray, M R AU - Mukherjee, G AU - Roychowdhury, S AU - Lahiri, T AD - Experimental Hematology Unit, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata, 700 026, West Bengal, India, manasrray@rediffmail.com Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 595 EP - 598 VL - 77 IS - 8 SN - 0340-0131, 0340-0131 KW - ragpickers KW - Health & Safety Science Abstracts; Pollution Abstracts KW - Smoking KW - Refuse KW - Landfills KW - Waste disposal sites KW - Socioeconomics KW - dermatitis KW - Environmental health KW - India, Delhi KW - Respiratory function 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/17359547?accountid=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=International+Archives+of+Occupational+and+Environmental+Health&rft.atitle=Respiratory+and+general+health+impairments+of+ragpickers+in+India%3A+a+study+in+Delhi&rft.au=Ray%2C+M+R%3BMukherjee%2C+G%3BRoychowdhury%2C+S%3BLahiri%2C+T&rft.aulast=Ray&rft.aufirst=M&rft.date=2004-11-01&rft.volume=77&rft.issue=8&rft.spage=595&rft.isbn=&rft.btitle=&rft.title=International+Archives+of+Occupational+and+Environmental+Health&rft.issn=03400131&rft_id=info:doi/10.1007%2Fs00420-004-0564-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Smoking; Refuse; Landfills; Waste disposal sites; Environmental health; dermatitis; Socioeconomics; Respiratory function; India, Delhi DO - http://dx.doi.org/10.1007/s00420-004-0564-8 ER - TY - JOUR T1 - Minimal influence of metallothionein over-expression on nickel carcinogenesis in mice AN - 17218048; 6906724 AB - Metallothionein (MT) is a metal-binding protein associated with tolerance to metals and oxidative stress. Nickel is a metal carcinogen potentially acting through oxidative attack on critical biomolecules. We investigated the role of MT in nickel carcinogenesis using MT-transgenic mice that constitutively over- express MT-I in all tissues tested. Groups of 25 male MT-transgenic and wild type (C57BL/6; WT) mice received intramuscular injections of nickel subsulfide (Ni sub(3)S sub(2)) in both thighs at doses of 0 (control), 0.5, or 1.0 mg/site at 12 weeks of age and were observed for 104 weeks. Injection site tumors (ISTs; primarily fibrosarcomas) started occurring 45 weeks after nickel injection and IST incidence was similar in the WT (control - 0%, 0.5 mg/site - 20%, 1.0 mg/site - 40%) and MT-transgenic mice (control - 0%, 0.5 mg/site - 28%, 1.0 mg/site - 29%.). At the 0.5 mg/site dose the average time to IST in MT- transgenic mice was 13 weeks shorter than in WT mice. Spontaneous lung tumors developed in 25% of control WT mice but none developed in control MT-transgenic mice. A nickel dose-related trend for increased lung tumors occurred in MT- transgenic mice but not in WT mice. Thus, the over-expression of MT did not significantly mitigate the carcinogenic response to nickel. JF - Toxicology Letters AU - Waalkes, Michael P AU - Liu, Jie AU - Kasprzak, Kazimierz S AU - Diwan, Bhalchandra A AD - Laboratory of Comparative Carcinogenesis, Inorganic Carcinogenesis Section, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, waalkes@niehs.nih.gov Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 357 EP - 364 PB - Elsevier Science Ireland Ltd., Elsevier House, Brookvale Plaza East Park Shannon, Co. Clare Ireland, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 153 IS - 3 SN - 0378-4274, 0378-4274 KW - mice KW - Toxicology Abstracts KW - Nickel KW - Carcinogenesis KW - Metallothionein KW - Mice KW - Sarcoma KW - Metals KW - Fibrosarcoma KW - Lung KW - Oxidative stress KW - Overexpression KW - Carcinogens KW - Transgenic mice KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17218048?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+Letters&rft.atitle=Minimal+influence+of+metallothionein+over-expression+on+nickel+carcinogenesis+in+mice&rft.au=Waalkes%2C+Michael+P%3BLiu%2C+Jie%3BKasprzak%2C+Kazimierz+S%3BDiwan%2C+Bhalchandra+A&rft.aulast=Waalkes&rft.aufirst=Michael&rft.date=2004-11-01&rft.volume=153&rft.issue=3&rft.spage=357&rft.isbn=&rft.btitle=&rft.title=Toxicology+Letters&rft.issn=03784274&rft_id=info:doi/10.1016%2Fj.toxlet.2004.06.003 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Fibrosarcoma; Metals; Metallothionein; Oxidative stress; Lung; Overexpression; Carcinogenesis; Nickel; Carcinogens; Transgenic mice DO - http://dx.doi.org/10.1016/j.toxlet.2004.06.003 ER - TY - JOUR T1 - Characteristics of particles sampled in southern Taiwan during the Asian dust storm periods in 2000 and 2001 AN - 16182733; 6034593 AB - Intensive field samplings followed by laboratory measurements were performed to characterize the particles collected at urban and rural sites in southern Taiwan during the Asian dust storm (ADS) periods in 2000 and 2001. These particles were size-resolvedly (cut sizes of eight-and ten-stages) sampled by two side-by-side micro-orifice uniform-deposited impactors (MOUDI). Results show that the concentrations of PM sub(2.5), PM sub(2.5-10) and PM sub(10) increased during the ADS periods and these PM sub(10) concentrations, >150 mu g m super(-3), were roughly 2 to 3 times higher than the average PM sub(10) concentrations measured in non-ADS periods. The concentrations of particle-bearing water-soluble ions including four crust-related species (Ca super(2+), Mg super(2+), Na super(+), and K super(+)), three secondary aerosol-associated species (SO sub(4) super(2-), NO sub(3) super(-), and NH sub(4) super(+)), and one sea-connected species (Cl super(-)) increased and their size distributions changed during the ADS periods in comparison with those during non-ADS periods, implying that they were partially from foreign sources. This supports the increasing health concerns for ADS. The SO sub(4) super(2-) had a major mode in fine size range (0.56-1.0 mu m) while the Ca super(2+) obtained a major mode in coarse size (3.2-5.6 mu m) at both sites. JF - Atmospheric Environment AU - Chen, S-J AU - Hsieh, L-T AU - Kao, M-J AU - Lin, W-Y AU - Huang, K-L AU - Lin, C-C AD - Department of Environmental Engineering and Science, National Pingtung University of Science and Technology, Nei Pu, PingTung 91201, Taiwan, chensj@mail.npust.edu.tw Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 5925 EP - 5934 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 38 IS - 35 SN - 1352-2310, 1352-2310 KW - Meteorological & Geoastrophysical Abstracts; Pollution Abstracts KW - Asian dust storm KW - PM sub(2.5) KW - PM sub(2.5-10) KW - Size distribution KW - Particle size KW - Ions KW - Taiwan KW - Atmospheric pollution KW - Dust storms KW - Particulate matter in urban air KW - Storms KW - Dust KW - Air pollution KW - Particle analysis KW - Air sampling KW - Urban atmospheric pollution KW - Air samples KW - Urban areas KW - Rural areas 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/16182733?accountid=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=Atmospheric+Environment&rft.atitle=Characteristics+of+particles+sampled+in+southern+Taiwan+during+the+Asian+dust+storm+periods+in+2000+and+2001&rft.au=Chen%2C+S-J%3BHsieh%2C+L-T%3BKao%2C+M-J%3BLin%2C+W-Y%3BHuang%2C+K-L%3BLin%2C+C-C&rft.aulast=Chen&rft.aufirst=S-J&rft.date=2004-11-01&rft.volume=38&rft.issue=35&rft.spage=5925&rft.isbn=&rft.btitle=&rft.title=Atmospheric+Environment&rft.issn=13522310&rft_id=info:doi/10.1016%2Fj.atmosenv.2004.07.006 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-07-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Atmospheric pollution; Dust storms; Particle analysis; Urban atmospheric pollution; Particulate matter in urban air; Air samples; Rural areas; Air pollution; Particle size; Ions; Air sampling; Storms; Dust; Urban areas; Taiwan DO - http://dx.doi.org/10.1016/j.atmosenv.2004.07.006 ER - TY - JOUR T1 - Laser capture microdissection, microarrays and the precise definition of a cancer cell AN - 1257725375; 16579559 AB - Most expression profiling studies of solid tumors have used biopsy samples containing large numbers of contaminating stromal and other cell types, thereby complicating any precise delineation of gene expression in nontumor versus tumor cell types. Combining laser capture microdissection, RNA amplification protocols, microarray technologies and our knowledge of the human genome sequence, it is possible to isolate pure populations of cells or even a single cell and interrogate the expression of thousands of sequences for the purpose of more precisely defining the biology of the tumor cell. Although many of the studies that currently allow for characterization of small sample preparations and single cells were performed utilizing noncancer cell types, and in some cases isolation protocols other than laser capture microdissection, a list of protocols are described that could be used for the expression analysis of individual tumor cells. Application of these experimental approaches to cancer studies may permit a more accurate definition of the biology of the cancer cell, so that ultimately, more specific targeted therapies can be developed. JF - Expert Review of Molecular Diagnostics AU - Player, Audrey AU - Barrett, J Carl AU - Kawasaki, Ernest S AD - National Cancer Institute, Advanced Technology Center, Microarray Facility, Gaithersburg, MD 20877, USA. Y1 - 2004/11// PY - 2004 DA - Nov 2004 SP - 831 EP - 840 PB - Future Science Group (FSG), Unitec House, 2 Albert Place London N3 1QB United Kingdom VL - 4 IS - 6 SN - 1473-7159, 1473-7159 KW - Biotechnology and Bioengineering Abstracts KW - Biopsy KW - Cancer KW - DNA microarrays KW - Gene expression KW - Genomes KW - Lasers KW - Nucleotide sequence KW - RNA KW - Solid tumors KW - Tumor cells KW - W 30900:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1257725375?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Laser+capture+microdissection%2C+microarrays+and+the+precise+definition+of+a+cancer+cell&rft.au=Player%2C+Audrey%3BBarrett%2C+J+Carl%3BKawasaki%2C+Ernest+S&rft.aulast=Player&rft.aufirst=Audrey&rft.date=2004-11-01&rft.volume=4&rft.issue=6&rft.spage=831&rft.isbn=&rft.btitle=&rft.title=Expert+Review+of+Molecular+Diagnostics&rft.issn=14737159&rft_id=info:doi/10.1586%2F14737159.4.6.831 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-12-01 N1 - Last updated - 2013-02-08 N1 - SubjectsTermNotLitGenreText - Gene expression; Genomes; RNA; Solid tumors; Nucleotide sequence; Biopsy; Lasers; DNA microarrays; Tumor cells; Cancer DO - http://dx.doi.org/10.1586/14737159.4.6.831 ER - TY - JOUR T1 - Structural mechanism for lipid activation of the Rac-specific GAP, beta2-chimaerin. AN - 67011434; 15507211 AB - The lipid second messenger diacylglycerol acts by binding to the C1 domains of target proteins, which translocate to cell membranes and are allosterically activated. Here we report the crystal structure at 3.2 A resolution of one such protein, beta2-chimaerin, a GTPase-activating protein for the small GTPase Rac, in its inactive conformation. The structure shows that in the inactive state, the N terminus of beta2-chimaerin protrudes into the active site of the RacGAP domain, sterically blocking Rac binding. The diacylglycerol and phospholipid membrane binding site on the C1 domain is buried by contacts with the four different regions of beta2-chimaerin: the N terminus, SH2 domain, RacGAP domain, and the linker between the SH2 and C1 domains. Phospholipid binding to the C1 domain triggers the cooperative dissociation of these interactions, allowing the N terminus to move out of the active site and thereby activating the enzyme. JF - Cell AU - Canagarajah, Bertram AU - Leskow, Federico Coluccio AU - Ho, Jonathan Yew Seng AU - Mischak, Harald AU - Saidi, Layla F AU - Kazanietz, Marcelo G AU - Hurley, James H AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD 20892, USA. Y1 - 2004/10/29/ PY - 2004 DA - 2004 Oct 29 SP - 407 EP - 418 VL - 119 IS - 3 SN - 0092-8674, 0092-8674 KW - Diglycerides KW - 0 KW - Neoplasm Proteins KW - beta-chimaerin KW - Protein Kinase C KW - EC 2.7.11.13 KW - rac GTP-Binding Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Mutagenesis, Site-Directed KW - Animals KW - COS Cells KW - Cercopithecus aethiops KW - Cell Membrane -- metabolism KW - Protein Structure, Tertiary KW - Mutation KW - Protein Transport -- physiology KW - rac GTP-Binding Proteins -- metabolism KW - Second Messenger Systems -- physiology KW - Neoplasm Proteins -- genetics KW - Neoplasm Proteins -- chemistry KW - Neoplasm Proteins -- metabolism KW - Diglycerides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67011434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Structural+mechanism+for+lipid+activation+of+the+Rac-specific+GAP%2C+beta2-chimaerin.&rft.au=Canagarajah%2C+Bertram%3BLeskow%2C+Federico+Coluccio%3BHo%2C+Jonathan+Yew+Seng%3BMischak%2C+Harald%3BSaidi%2C+Layla+F%3BKazanietz%2C+Marcelo+G%3BHurley%2C+James+H&rft.aulast=Canagarajah&rft.aufirst=Bertram&rft.date=2004-10-29&rft.volume=119&rft.issue=3&rft.spage=407&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-12-17 N1 - Date created - 2004-10-27 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1XA6; PDB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unveiling functional protein motions with picosecond x-ray crystallography and molecular dynamics simulations. AN - 67017909; 15489270 AB - A joint analysis of all-atom molecular dynamics (MD) calculations and picosecond time-resolved x-ray structures was performed to gain single-molecule insights into mechanisms of protein function. Ensemble-averaged MD simulations of the L29F mutant of myoglobin after ligand dissociation reproduce the direction, amplitude, and time scales of crystallographically determined structural changes. This close agreement with experiments at comparable resolution in space and time validates the individual MD trajectories. From 1,700 single-molecule trajectories, we identified and structurally characterized a conformational switch that directs dissociated ligands to one of two nearby protein cavities. Subsequent ligand migration proceeds through a network of transiently interconnected internal cavities, with passage between them involving correlated protein-ligand motions. The simulations also suggest how picosecond protein motions modulate the functional dissociation of oxygen and suppress the geminate recombination of toxic carbon monoxide. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hummer, Gerhard AU - Schotte, Friedrich AU - Anfinrud, Philip A AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA. hummer@helix.nih.gov Y1 - 2004/10/26/ PY - 2004 DA - 2004 Oct 26 SP - 15330 EP - 15334 VL - 101 IS - 43 SN - 0027-8424, 0027-8424 KW - Proteins KW - 0 KW - Carbon Monoxide KW - 7U1EE4V452 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Oxygen -- chemistry KW - Crystallography, X-Ray KW - Carbon Monoxide -- chemistry KW - Protein Conformation KW - Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67017909?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Unveiling+functional+protein+motions+with+picosecond+x-ray+crystallography+and+molecular+dynamics+simulations.&rft.au=Hummer%2C+Gerhard%3BSchotte%2C+Friedrich%3BAnfinrud%2C+Philip+A&rft.aulast=Hummer&rft.aufirst=Gerhard&rft.date=2004-10-26&rft.volume=101&rft.issue=43&rft.spage=15330&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 - 2004-12-09 N1 - Date created - 2004-10-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 2001 Nov 20;40(46):13802-15 [11705369] Nature. 2000 Feb 24;403(6772):921-3 [10706294] Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8704-9 [12847289] J Am Chem Soc. 2003 Nov 12;125(45):13804-18 [14599220] Biophys J. 2003 Dec;85(6):3612-23 [14645054] Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5998-6002 [15067128] Biophys J. 2004 Jun;86(6):3855-62 [15189882] Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2058-63 [10681426] Nature. 1964 Jul 11;203:182-3 [14207238] Nature. 2000 Mar 9;404(6774):205-8 [10724176] Acc Chem Res. 2001 Feb;34(2):137-44 [11263872] J Mol Biol. 1966 Oct 28;21(1):199-202 [5969763] Biochemistry. 1975 Dec 2;14(24):5355-73 [1191643] J Mol Biol. 1979 Aug 15;132(3):343-68 [533895] Biochemistry. 1984 Jun 19;23(13):2849-57 [6466620] Proc Natl Acad Sci U S A. 1985 Apr;82(7):2034-8 [3856881] Science. 1991 Dec 13;254(5038):1598-603 [1749933] J Biol Chem. 1992 Jul 15;267(20):14443-50 [1629229] J Biol Chem. 1993 Aug 25;268(24):17908-16 [8349675] Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9135-9 [8415667] Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9547-51 [8415739] J Mol Biol. 1993 Nov 5;234(1):140-55 [8230194] Nature. 1994 Oct 27;371(6500):808-12 [7935843] Science. 1995 Aug 18;269(5226):962-6 [7638619] J Mol Biol. 1996 Mar 8;256(4):762-74 [8642596] Science. 1996 Dec 6;274(5293):1726-9 [8939867] Nat Struct Biol. 1997 Mar;4(3):202-8 [9164461] Nat Struct Biol. 1997 Mar;4(3):209-14 [9164462] Biophys J. 1998 Feb;74(2 Pt 1):789-802 [9533692] Science. 1999 Apr 16;284(5413):473-6 [10205052] Science. 2003 Jun 20;300(5627):1944-7 [12817148] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ceramide, a target for antiretroviral therapy. AN - 67014609; 15489273 AB - Studies of ceramide metabolism and function in a wide range of biological processes have revealed a role for this lipid in regulating key cellular responses. Our research on the role of sphingolipids in HIV entry has led to the hypothesis that modulation of ceramide levels in target cells affects their susceptibility to HIV infection by rearranging HIV receptors. Cellular ceramide levels were modulated by application of pharmacological agents such as N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide), by treatment with sphingomyelinase (Smase), or by exogenous addition of long-chain ceramide, and determined after metabolic incorporation of [3H]sphingosine. Infectivity assays were performed by using a HeLa-derived indicator cell line, TZM-bl, CD4+ lymphocytes, and monocytes. We observed a dose-dependent inhibition by 4-HPR of infection of TZM-bl cells by a broad range of HIV-1 isolates at low micromolar concentrations with an IC50 of <1 microM for most isolates tested. Nearly complete inhibition was seen at 5 microM, a dose that enhanced ceramide levels by 50-100%, yet was nontoxic to the cells. Treating cells with other pharmacological agents that enhanced ceramide levels, with Smase, or exogenous addition of long-chain ceramide also resulted in inhibition of HIV-1 infection. Enhancing ceramide levels in CD4+ lymphocytes and in monocyte-derived macrophages with 4-HPR or Smase significantly reduced infectivity without toxicity. The minimal toxicity of normal cells exposed to 4-HPR should make the drug exceedingly suitable as an anti-HIV therapeutic. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Finnegan, Catherine M AU - Rawat, Satinder S AU - Puri, Anu AU - Wang, Ji Ming AU - Ruscetti, Francis W AU - Blumenthal, Robert AD - Laboratories of Experimental and Computational Biology, Molecular Immunoregulation, and Experimental Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. Y1 - 2004/10/26/ PY - 2004 DA - 2004 Oct 26 SP - 15452 EP - 15457 VL - 101 IS - 43 SN - 0027-8424, 0027-8424 KW - Anti-HIV Agents KW - 0 KW - Ceramides KW - Fenretinide KW - 187EJ7QEXL KW - Index Medicus KW - Fenretinide -- pharmacology KW - Cells, Cultured KW - Humans KW - CD4-Positive T-Lymphocytes -- virology KW - Adult KW - Membrane Fusion -- drug effects KW - Chemotaxis, Leukocyte KW - Anti-HIV Agents -- pharmacology KW - Ceramides -- antagonists & inhibitors KW - HIV-1 -- physiology KW - Ceramides -- biosynthesis KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67014609?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Ceramide%2C+a+target+for+antiretroviral+therapy.&rft.au=Finnegan%2C+Catherine+M%3BRawat%2C+Satinder+S%3BPuri%2C+Anu%3BWang%2C+Ji+Ming%3BRuscetti%2C+Francis+W%3BBlumenthal%2C+Robert&rft.aulast=Finnegan&rft.aufirst=Catherine&rft.date=2004-10-26&rft.volume=101&rft.issue=43&rft.spage=15452&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 - 2004-12-09 N1 - Date created - 2004-10-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Antimicrob Agents Chemother. 2002 Jun;46(6):1896-905 [12019106] Blood. 2002 Jun 15;99(12):4298-306 [12036855] J Biol Chem. 2002 Jul 19;277(29):25847-50 [12011103] J Exp Med. 2002 Aug 5;196(3):293-301 [12163558] J Virol. 2002 Nov;76(22):11584-95 [12388719] FEBS Lett. 2002 Oct 30;531(1):47-53 [12401201] Nat Biotechnol. 2002 Nov;20(11):1151-4 [12355096] J Biol Chem. 2003 Jan 31;278(5):3153-61 [12431990] Nat Med. 2003 Mar;9(3):322-30 [12563314] Biochim Biophys Acta. 2003 Jul 11;1614(1):36-50 [12873764] Mol Membr Biol. 2003 Jul-Sep;20(3):243-54 [12893532] Exp Cell Res. 2003 Nov 15;291(1):36-45 [14597406] J Biol Chem. 2004 Jan 2;279(1):704-12 [14570906] J Virol. 2004 Feb;78(3):1375-83 [14722292] Cancer Res. 1993 Nov 15;53(22):5374-6 [8221674] J Lipid Res. 1999 Nov;40(11):1978-89 [10553001] J Biol Chem. 2000 Mar 24;275(12):9078-84 [10722759] EMBO Rep. 2000 Aug;1(2):190-6 [11265761] J Virol. 2001 Apr;75(8):3779-90 [11264367] Cancer Res. 2001 Jul 1;61(13):5102-5 [11431347] AIDS Res Hum Retroviruses. 2001 Jul 20;17(11):1009-19 [11485618] J Clin Virol. 2001 Oct;22(3):217-27 [11564586] J Virol. 2002 Feb;76(4):1802-15 [11799176] J Immunol. 2002 Apr 15;168(8):4121-6 [11937572] Cell. 1995 Aug 11;82(3):405-14 [7634330] J Lipid Res. 1997 May;38(5):969-80 [9186914] Biophys J. 1999 Jan;76(1 Pt 1):342-50 [9876146] Can J Biochem Physiol. 1959 Aug;37(8):911-7 [13671378] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial AN - 199008553; 15500895 AB - The issue of whether regular use of an inhaled beta2-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial. Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine (Arg/Arg), rather than glycine (Gly/Gly), at aminoacid residue 16 of the beta2-adrenergic receptor. However, the existence of any genotype-dependent difference has not been tested in a prospective clinical trial. Patients with mild asthma, not using a controller medication, were enrolled in pairs matched for forced expiratory volume in 1 s (FEV1) according to whether they had the Arg/Arg (n=37; four of 41 matches withdrew before randomisation) or Gly/Gly (n=41) genotype. Regularly scheduled treatment with albuterol or placebo was given in a masked, cross-over design, for 16-week periods. During the study, as-needed albuterol use was discontinued and ipratropium bromide was used as needed. Morning peak expiratory flow rate (PEFR) was the primary outcome variable. The primary comparisons were between treatment period for each genotype; the secondary outcome was a treatment by genotype effect. Analyses were by intention to treat. During the run-in period, when albuterol use was kept to a minimum, patients with the Arg/Arg genotype had an increase in morning PEFR of 23 L/min (p=0.0162); the change in patients with the Gly/Gly genotype was not significant (2 L/min; p=0.8399). During randomised treatment, patients with the Gly/Gly genotype had an increase in morning PEFR during treatment with regularly scheduled albuterol compared with placebo (14 L/min [95% CI 3 to 25]; p=0.0175). By contrast, patients with the Arg/Arg genotype had lower morning PEFR during treatment with albuterol than during the placebo period, when albuterol use was limited (-10 L/min [-19 to -2]; p=0.0209). The genotype-attributable treatment difference was therefore -24 L/min (-37 to -12; p=0.0003). There were similar genotype-specific effects in FEV1, symptoms, and use of supplementary reliever medication. Genotype at the 16th aminoacid residue of the beta2-adrenergic receptor affects the long-term response to albuterol use. Bronchodilator treatments avoiding albuterol may be appropriate for patients with the Arg/Arg genotype. JF - The Lancet AU - Israel, Elliot AU - Chinchilli, Vernon M AU - Ford, Jean G AU - Boushey, Homer A AU - et al Y1 - 2004///Oct 23-Oct 29, PY - 2004 DA - Oct 23-Oct 29, 2004 SP - 1505 EP - 12 CY - London PB - Elsevier Limited VL - 364 IS - 9444 SN - 01406736 KW - Medical Sciences KW - Adrenergic beta-Agonists KW - Receptors, Adrenergic, beta-2 KW - Albuterol KW - Asthma KW - Medical treatment KW - Genotype & phenotype KW - Clinical trials KW - Prescription drugs KW - Drug Administration Schedule KW - Peak Expiratory Flow Rate KW - Double-Blind Method KW - Polymorphism, Genetic KW - Humans KW - Asthma -- genetics KW - Forced Expiratory Volume KW - Asthma -- physiopathology KW - Genotype KW - Single-Blind Method KW - Adult KW - Cross-Over Studies KW - Middle Aged KW - Metered Dose Inhalers KW - Administration, Inhalation KW - Adolescent KW - Male KW - Female KW - Albuterol -- administration & dosage KW - Asthma -- drug therapy KW - Receptors, Adrenergic, beta-2 -- genetics KW - Adrenergic beta-Agonists -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/199008553?accountid=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=Use+of+regularly+scheduled+albuterol+treatment+in+asthma%3A+genotype-stratified%2C+randomised%2C+placebo-controlled+cross-over+trial&rft.au=Israel%2C+Elliot%3BChinchilli%2C+Vernon+M%3BFord%2C+Jean+G%3BBoushey%2C+Homer+A%3Bet+al&rft.aulast=Israel&rft.aufirst=Elliot&rft.date=2004-10-23&rft.volume=364&rft.issue=9444&rft.spage=1505&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. Oct 23-Oct 29, 2004 N1 - Document feature - Diagrams; Charts; Tables; Graphs; References N1 - Last updated - 2015-02-07 N1 - CODEN - LANCAO ER - TY - JOUR T1 - Analyzing the Handoff of DNA from UvrA to UvrB Utilizing DNA-Protein Photoaffinity Labeling AN - 17756248; 6062262 AB - To better define the molecular architecture of nucleotide excision repair intermediates it is necessary to identify the specific domains of UvrA, UvrB, and UvrC that are in close proximity to DNA damage during the repair process. One key step of nucleotide excision repair that is poorly understood is the transfer of damaged DNA from UvrA to UvrB, prior to incision by UvrC. To study this transfer, we have utilized two types of arylazido-modified photoaffinity reagents that probe residues in the Uvr proteins that are closest to either the damaged or non-damaged strands. The damaged strand probes consisted of dNTP analogs linked to a terminal arylazido moiety. These analogs were incorporated into double-stranded DNA using DNA polymerase beta and functioned as both the damage site and the cross-linking reagent. The non-damaged strand probe contained an arylazido moiety coupled to a phosphorothioate-modified backbone of an oligonucleotide opposite the damaged strand, which contained an internal fluorescein adduct. Six site-directed mutants of Bacillus caldotenax UvrB located in different domains within the protein (Y96A, E99A, R123A, R183E, F249A, and D510A), and two domain deletions (delta2 and deltabeta-hairpin), were assayed. Data gleaned from these mutants suggest that the handoff of damaged DNA from UvrA to UvrB proceeds in a three-step process: 1) UvrA and UvrB bind to the damaged site, with UvrA in direct contact; 2) a transfer reaction with UvrB contacting mostly the non-damaged DNA strand; 3) lesion engagement by the damage recognition pocket of UvrB with concomitant release of UvrA. JF - Journal of Biological Chemistry AU - Dellavecchia, Matthew J AU - Croteau, Deborah L AU - Skorvaga, Milan AU - Dezhurov, Sergey V AU - Lavrik, Olga I AU - Van Houten, Bennett AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina Y1 - 2004/10/22/ PY - 2004 DA - 2004 Oct 22 SP - 45245 EP - 45256 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 - 279 IS - 43 SN - 0021-9258, 0021-9258 KW - UvrB protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Bacillus caldotenax KW - DNA adducts KW - Deletion KW - uvrA protein KW - Probes KW - Oligonucleotides KW - fluorescein KW - DNA damage KW - Nucleotide excision repair KW - DNA-directed DNA polymerase KW - Fluorescent indicators KW - Bacillus KW - J 02725:DNA KW - N 14030:DNA: biosynthesis, repair & replication cycle UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17756248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Analyzing+the+Handoff+of+DNA+from+UvrA+to+UvrB+Utilizing+DNA-Protein+Photoaffinity+Labeling&rft.au=Dellavecchia%2C+Matthew+J%3BCroteau%2C+Deborah+L%3BSkorvaga%2C+Milan%3BDezhurov%2C+Sergey+V%3BLavrik%2C+Olga+I%3BVan+Houten%2C+Bennett&rft.aulast=Dellavecchia&rft.aufirst=Matthew&rft.date=2004-10-22&rft.volume=279&rft.issue=43&rft.spage=45245&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus caldotenax; Bacillus; DNA-directed DNA polymerase; Nucleotide excision repair; Fluorescent indicators; Oligonucleotides; DNA damage; Deletion; uvrA protein; DNA adducts; Probes; fluorescein ER - TY - JOUR T1 - Architecture of P2Y nucleotide receptors: structural comparison based on sequence analysis, mutagenesis, and homology modeling. AN - 66973866; 15481977 AB - Human P2Y receptors encompass at least eight subtypes of Class A G protein-coupled receptors (GPCRs), responding to adenine and/or uracil nucleotides. Using a BLAST search against the Homo sapiens subset of the SWISS-PROT and TrEMBL databases, we identified 68 proteins showing high similarity to P2Y receptors. To address the problem of low sequence identity between rhodopsin and the P2Y receptors, we performed a multiple-sequence alignment of the retrieved proteins and the template bovine rhodopsin, combining manual identification of the transmembrane domains (TMs) with automatic techniques. The resulting phylogenetic tree delineated two distinct subgroups of P2Y receptors: Gq-coupled subtypes (e.g., P2Y1) and those coupled to Gi (e.g., P2Y12). On the basis of sequence comparison we mutated three Tyr residues of the putative P2Y1 binding pocket to Ala and Phe and characterized pharmacologically the mutant receptors expressed in COS-7 cells. The mutation of Y306 (7.35, site of a cationic residue in P2Y12) or Y203 in the second extracellular loop selectively decreased the affinity of the agonist 2-MeSADP, and the Y306F mutation also reduced antagonist (MRS2179) affinity by 5-fold. The Y273A (6.48) mutation precluded the receptor activation without a major effect on the ligand-binding affinities, but the Y273F mutant receptor still activated G proteins with full agonist affinity. Thus, we have identified new recognition elements to further define the P2Y1 binding site and related these to other P2Y receptor subtypes. Following sequence-based secondary-structure prediction, we constructed complete models of all the human P2Y receptors by homology to rhodopsin. Ligand docking on P2Y1 and P2Y12 receptor models was guided by mutagenesis results, to identify the residues implicated in the binding process. Different sets of cationic residues in the two subgroups appeared to coordinate phosphate-bearing ligands. Within the P2Y1 subgroup these residues are R3.29, K/R6.55, and R7.39. Within the P2Y12 subgroup, the only residue in common with P2Y1 is R6.55, and the role of R3.29 in TM3 seems to be fulfilled by a Lys residue in EL2, whereas the R7.39 in TM7 seems to be substituted by K7.35. Thus, we have identified common and distinguishing features of P2Y receptor structure and have proposed modes of ligand binding for the two representative subtypes that already have well-developed ligands. JF - Journal of medicinal chemistry AU - Costanzi, Stefano AU - Mamedova, Liaman AU - Gao, Zhan-Guo 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 - 2004/10/21/ PY - 2004 DA - 2004 Oct 21 SP - 5393 EP - 5404 VL - 47 IS - 22 SN - 0022-2623, 0022-2623 KW - Membrane Proteins KW - 0 KW - P2RY1 protein, human KW - P2RY12 protein, human KW - Purinergic P2 Receptor Agonists KW - Purinergic P2 Receptor Antagonists KW - Receptors, Purinergic P2 KW - Receptors, Purinergic P2Y1 KW - Receptors, Purinergic P2Y12 KW - Rhodopsin KW - 9009-81-8 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - COS Cells KW - Membrane Proteins -- chemistry KW - Models, Molecular KW - Humans KW - Amino Acid Sequence KW - Radioligand Assay KW - Membrane Proteins -- agonists KW - Mutagenesis, Site-Directed KW - Cattle KW - Sequence Alignment KW - Molecular Sequence Data KW - Membrane Proteins -- antagonists & inhibitors KW - Rhodopsin -- chemistry KW - Hydrogen Bonding KW - Receptors, Purinergic P2 -- metabolism KW - Receptors, Purinergic P2 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66973866?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Architecture+of+P2Y+nucleotide+receptors%3A+structural+comparison+based+on+sequence+analysis%2C+mutagenesis%2C+and+homology+modeling.&rft.au=Costanzi%2C+Stefano%3BMamedova%2C+Liaman%3BGao%2C+Zhan-Guo%3BJacobson%2C+Kenneth+A&rft.aulast=Costanzi&rft.aufirst=Stefano&rft.date=2004-10-21&rft.volume=47&rft.issue=22&rft.spage=5393&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 - 2004-12-03 N1 - Date created - 2004-10-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Trends Biochem Sci. 2000 Mar;25(3):147-50 [10694887] Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11023-7 [10500117] J Biol Chem. 2000 Apr 14;275(15):10767-71 [10753868] Science. 2000 Aug 4;289(5480):739-45 [10926528] Mol Pharmacol. 2001 Jul;60(1):1-19 [11408595] Biochemistry. 2001 Jul 3;40(26):7761-72 [11425302] J Med Chem. 2001 Sep 13;44(19):3092-108 [11543678] Biochemistry. 2001 Oct 2;40(39):11932-7 [11570894] Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5982-7 [11972040] Biochim Biophys Acta. 2002 May 23;1582(1-3):81-8 [12069813] J Med Chem. 2002 Sep 12;45(19):4057-93 [12213051] J Med Chem. 2002 Sep 26;45(20):4471-84 [12238926] Mol Pharmacol. 2002 Nov;62(5):1249-57 [12391289] J Mol Graph Model. 2003 Jan;21(4):253-62 [12479925] Trends Pharmacol Sci. 2003 Feb;24(2):52-5 [12559763] Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1978-83 [12578987] Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2290-5 [12601165] J Biol Chem. 2003 Mar 14;278(11):9869-74 [12522134] Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4903-8 [12679517] Blood. 2003 May 15;101(10):3908-14 [12560222] Mol Pharmacol. 2003 Jun;63(6):1256-72 [12761335] Mol Pharmacol. 2003 Jun;63(6):1356-63 [12761346] J Biol Chem. 2003 Jul 11;278(28):25600-6 [12724320] Nature. 2004 May 13;429(6988):188-93 [15141213] FEBS Lett. 1986 Sep 15;205(2):303-8 [3743779] Mol Biol Evol. 1987 Jul;4(4):406-25 [3447015] Proteins. 1992 Apr;12(4):345-64 [1579569] Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915-9 [1438297] J Mol Biol. 1993 Dec 5;234(3):779-815 [8254673] Nucleic Acids Res. 1994 Nov 11;22(22):4673-80 [7984417] Protein Sci. 1994 Sep;3(9):1582-96 [7833817] Methods Enzymol. 1996;266:540-53 [8743705] Comput Appl Biosci. 1995 Dec;11(6):681-4 [8808585] Drug Des Discov. 1995 Nov;13(2):133-54 [8872457] Mol Pharmacol. 1997 Sep;52(3):499-507 [9281613] Nucleic Acids Res. 1997 Dec 15;25(24):4876-82 [9396791] J Med Chem. 1998 Apr 23;41(9):1456-66 [9554879] Biochemistry. 1999 Mar 23;38(12):3498-507 [10090736] J Biol Chem. 1999 May 21;274(21):14639-47 [10329657] Bioinformatics. 1999 May;15(5):413-21 [10366661] J Med Chem. 2000 Mar 9;43(5):829-42 [10715151] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2. AN - 66995524; 15494606 AB - The bacterial enzyme carboxypeptidase G2 (CPDG2) rapidly hydrolyzes methotrexate to inactive metabolites. We administered recombinant CPDG2 (2000 U) intrathecally to seven cancer patients 3 to 9 hours after they had received an accidental overdose of intrathecal methotrexate (median dose = 364 mg; range = 155-600 mg). Four of the seven patients had cerebrospinal fluid (CSF) exchange to remove methotrexate before CPDG2 administration. Immediate symptoms of the methotrexate overdoses included seizures (n = 5), coma (n = 2), and cardiopulmonary compromise (n = 2). Before CPDG2 administration, the median concentrations of methotrexate in CSF were 264 microM (range = 97-510 microM) among patients who had CSF exchange and 8050 microM (range = 2439-16 500 microM) among patients who did not. After intrathecal CPDG2 administration, methotrexate concentrations in CSF declined by more than 98%. All patients recovered completely from the intrathecal methotrexate overdose except for two patients who had memory impairments. Antibodies to CPDG2 were not detected in plasma after treatment with intrathecal CPDG2. Intrathecal CPDG2 is well tolerated, rapidly decreases CSF methotrexate concentrations, and appears to be efficacious for treating accidental intrathecal methotrexate overdoses. JF - Journal of the National Cancer Institute AU - Widemann, Brigitte C AU - Balis, Frank M AU - Shalabi, Aiman AU - Boron, Matthew AU - O'Brien, Michelle AU - Cole, Diane E AU - Jayaprakash, Nalini AU - Ivy, Percy AU - Castle, Valerie AU - Muraszko, Karin AU - Moertel, Christopher L AU - Trueworthy, Robert AU - Hermann, Robert C AU - Moussa, Ali AU - Hinton, Stuart AU - Reaman, Gregory AU - Poplack, David AU - Adamson, Peter C AD - Pediatric Oncology Branch, Pediatric Oncology Branch, National Cancer Institute, 10 Center Dr., Bldg. 10, Rm. 13C103, Bethesda, MD 20892-1920, USA. bw42y@nih.gov Y1 - 2004/10/20/ PY - 2004 DA - 2004 Oct 20 SP - 1557 EP - 1559 VL - 96 IS - 20 KW - Antimetabolites, Antineoplastic KW - 0 KW - Recombinant Proteins KW - gamma-Glutamyl Hydrolase KW - EC 3.4.19.9 KW - Methotrexate KW - YL5FZ2Y5U1 KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Drainage KW - Humans KW - Clinical Trials as Topic KW - Aged KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Injections, Spinal KW - Adult KW - Drug Overdose KW - Middle Aged KW - Recombinant Proteins -- therapeutic use KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma -- drug therapy KW - Female KW - Male KW - Neoplasms -- drug therapy KW - gamma-Glutamyl Hydrolase -- administration & dosage KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Antimetabolites, Antineoplastic -- cerebrospinal fluid KW - Neoplasms -- cerebrospinal fluid KW - Methotrexate -- adverse effects KW - Antimetabolites, Antineoplastic -- adverse effects KW - Methotrexate -- cerebrospinal fluid KW - gamma-Glutamyl Hydrolase -- therapeutic use KW - Methotrexate -- administration & dosage KW - Medication Errors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66995524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Treatment+of+accidental+intrathecal+methotrexate+overdose+with+intrathecal+carboxypeptidase+G2.&rft.au=Widemann%2C+Brigitte+C%3BBalis%2C+Frank+M%3BShalabi%2C+Aiman%3BBoron%2C+Matthew%3BO%27Brien%2C+Michelle%3BCole%2C+Diane+E%3BJayaprakash%2C+Nalini%3BIvy%2C+Percy%3BCastle%2C+Valerie%3BMuraszko%2C+Karin%3BMoertel%2C+Christopher+L%3BTrueworthy%2C+Robert%3BHermann%2C+Robert+C%3BMoussa%2C+Ali%3BHinton%2C+Stuart%3BReaman%2C+Gregory%3BPoplack%2C+David%3BAdamson%2C+Peter+C&rft.aulast=Widemann&rft.aufirst=Brigitte&rft.date=2004-10-20&rft.volume=96&rft.issue=20&rft.spage=1557&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 - 2004-11-02 N1 - Date created - 2004-10-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 2005 Apr 20;97(8):609-10; author reply 610-1 [15840887] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase II trial of neoadjuvant docetaxel and capecitabine for locally advanced breast cancer. AN - 67002697; 15501952 AB - This study evaluated the toxicity and efficacy of docetaxel/capecitabine as neoadjuvant treatment for stage 2/3 breast cancer. Subjects with newly diagnosed invasive stage 2 and 3 breast cancer were eligible. The first cohort of patients was treated at dose A with neoadjuvant docetaxel (75 mg/m(2) i.v. day 1) and capecitabine (1000 mg/m(2) orally twice daily days 2-15) for four cycles. A second cohort of subjects was treated with a reduced dose, dose B, of docetaxel (60 mg/m(2) i.v. day 1) and capecitabine (937.5 mg/m(2) orally twice daily days 2-15). Thirty patients were enrolled. Eight of 10 patients treated at dose A required dose reductions of either docetaxel or capecitabine secondary to grade 3 or 4 toxicities: mucositis (1), hand-foot syndrome (3), diarrhea (2), perirectal abscess (1), and neutropenia (2). Because of a high rate of dose reductions, the next 20 patients were treated at dose B. The mean cumulative administered dose of docetaxel was 285 and 231 mg/m(2) at dose A and dose B, respectively. For capecitabine, the mean cumulative dose at dose A and B were similar at 1585 and 1627 mg/m(2)/day, respectively. The overall clinical response rate was 90% with 31% of patients having a complete response and 59% having a partial response. A pathological complete response in the breast was achieved in 10% of patients after four cycles of docetaxel/capecitabine. Docetaxel/capecitabine is a highly active regimen in the neoadjuvant setting. Neoadjuvant therapy with 75 mg/m(2) docetaxel and 1600 mg/m(2)/day days 2-15 is recommended. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Lebowitz, Peter F AU - Eng-Wong, Jennifer AU - Swain, Sandra M AU - Berman, Arlene AU - Merino, Maria J AU - Chow, Catherine K AU - Venzon, David AU - Zia, Farah AU - Danforth, David AU - Liu, Edison AU - Zujewski, Joanne AD - Medical Oncology Clinical Research Unit, Cancer Therapeutics Branch, Laboratory of Pathology, Biostatistics and Data Management, and Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 6764 EP - 6769 VL - 10 IS - 20 SN - 1078-0432, 1078-0432 KW - Taxoids KW - 0 KW - Deoxycytidine KW - 0W860991D6 KW - docetaxel KW - 15H5577CQD KW - Capecitabine KW - 6804DJ8Z9U KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Administration, Oral KW - Infusions, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Neoadjuvant Therapy KW - Aged KW - Peripheral Nervous System Diseases -- chemically induced KW - Neutropenia KW - Diarrhea -- chemically induced KW - Adult KW - Fluorouracil -- analogs & derivatives KW - Treatment Outcome KW - Middle Aged KW - Female KW - Breast Neoplasms -- drug therapy KW - Deoxycytidine -- adverse effects KW - Breast Neoplasms -- pathology KW - Deoxycytidine -- analogs & derivatives KW - Taxoids -- adverse effects KW - Deoxycytidine -- therapeutic use KW - Deoxycytidine -- administration & dosage KW - Taxoids -- therapeutic use KW - Breast Neoplasms -- surgery KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Taxoids -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67002697?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+phase+II+trial+of+neoadjuvant+docetaxel+and+capecitabine+for+locally+advanced+breast+cancer.&rft.au=Lebowitz%2C+Peter+F%3BEng-Wong%2C+Jennifer%3BSwain%2C+Sandra+M%3BBerman%2C+Arlene%3BMerino%2C+Maria+J%3BChow%2C+Catherine+K%3BVenzon%2C+David%3BZia%2C+Farah%3BDanforth%2C+David%3BLiu%2C+Edison%3BZujewski%2C+Joanne&rft.aulast=Lebowitz&rft.aufirst=Peter&rft.date=2004-10-15&rft.volume=10&rft.issue=20&rft.spage=6764&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 - 2005-03-29 N1 - Date created - 2004-10-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The orphan nuclear receptor constitutive active/androstane receptor is essential for liver tumor promotion by phenobarbital in mice. AN - 66986289; 15492232 AB - Hepatocellular carcinoma (HCC) is known to progress through a step often called tumor promotion. Phenobarbital (PB) is the prototype of nongenotoxic cacinogens that promote HCC in rodents. The molecular target of PB to elicit the promotion has been the subject of intense investigations over the last 30 years since it was discovered. The nuclear receptor constitutive active/androstane receptor (CAR) is activated by PB as well as by various other xenobiotics such as therapeutic drugs and environmental pollutants. CAR activation results in the transcriptional induction of numerous hepatic genes including those that encode xenobiotic-metabolizing enzymes such as a set of cytochrome P450s. In addition to PB, many CAR activators are nongenotoxic carcinogens, but the role of CAR in liver tumor promotion remains unexplored. Using Car(-/-) mice, we have here examined tumor promotion by chronic treatment with PB in drinking water after tumor initiation with a single dose of the genotoxic carcinogen diethylnitrosamine. None of the Car(-/-) mice developed either eosinophilic foci or advanced liver tumors, whereas all Car(+/+) mice developed HCC and/or adenoma by 39 weeks. The results indicate that CAR is the molecular target of promotion by PB and that activation of this receptor is an essential requirement for liver tumor development. JF - Cancer research AU - Yamamoto, Yukio AU - Moore, Rick AU - Goldsworthy, Thomas L AU - Negishi, Masahiko AU - Maronpot, Robert R AD - Laboratories of Reproductive and Developmental Toxicology and Experimental Pathology, National Institute of Environmental Health Sciences, National Institutes of Health, Research TrianglePark, NC, USA. Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 7197 EP - 7200 VL - 64 IS - 20 SN - 0008-5472, 0008-5472 KW - Receptors, Cytoplasmic and Nuclear KW - 0 KW - Transcription Factors KW - constitutive androstane receptor KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Genotype KW - Animals KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Mice KW - Receptors, Cytoplasmic and Nuclear -- physiology KW - Transcription Factors -- physiology KW - Liver Neoplasms, Experimental -- genetics KW - Liver Neoplasms, Experimental -- pathology KW - Liver Neoplasms, Experimental -- etiology KW - Liver Neoplasms, Experimental -- chemically induced KW - Transcription Factors -- deficiency KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Receptors, Cytoplasmic and Nuclear -- deficiency KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66986289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+orphan+nuclear+receptor+constitutive+active%2Fandrostane+receptor+is+essential+for+liver+tumor+promotion+by+phenobarbital+in+mice.&rft.au=Yamamoto%2C+Yukio%3BMoore%2C+Rick%3BGoldsworthy%2C+Thomas+L%3BNegishi%2C+Masahiko%3BMaronpot%2C+Robert+R&rft.aulast=Yamamoto&rft.aufirst=Yukio&rft.date=2004-10-15&rft.volume=64&rft.issue=20&rft.spage=7197&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 - 2004-12-03 N1 - Date created - 2004-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Restoration of bone morphogenetic protein receptor type II expression leads to a decreased rate of tumor growth in bladder transitional cell carcinoma cell line TSU-Pr1. AN - 66983447; 15492256 AB - Bone morphogenetic proteins (BMPs), potential regulators of cellular growth and metastasis that signal through an interaction with plasma membrane receptors, have been suggested to be important regulators of malignant cells. The present study was carried out to evaluate the potential role of BMP receptor (BMP-R) types IA, IB, and II in bladder transitional cell carcinoma (TCC) cells. Initially, we investigated the expression of these BMP-Rs in 30 archival tissues of human bladder TCC using immunohistochemistry; 10 benign bladder specimens were used for comparison. The results demonstrated that the expression of BMP-Rs is localized preferentially to the transitional epithelium and that there was a significant association between loss of BMP-RII expression and tumor grade. To find a cell line that can serve as a model system for clinical observation, we subsequently examined sensitivity to BMP-4 and expression of BMP-RII, BMP-RIA, and BMP-RIB in three human bladder cancer cell lines, TCC-Sup, RT4, and TSU-Pr1. Of the three cell lines, TSU-Pr1 exhibited a decreased level of BMP-RII expression and was resistant to the growth-inhibitory effect of BMP-4. Overexpression of BMP-RII in TSU-Pr1 cells not only restored BMP-4 responsiveness but also significantly decreased tumorigenicity in vivo. Taken together, these results demonstrate that human bladder TCC tissues have a frequent loss of BMP-RII expression and that overexpression of BMP-RII leads to restoration of BMP signaling and decreased tumor growth in the human bladder TCC cell line TSU-Pr1. JF - Cancer research AU - Kim, Isaac Yi AU - Lee, Dong-Hyeon AU - Lee, Dug Keun AU - Kim, Wun Jae AU - Kim, Moses M AU - Morton, Ronald A AU - Lerner, Seth P AU - Kim, Seong Jin AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland, USA. kis@dce41.nci.nih.gov Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 7355 EP - 7360 VL - 64 IS - 20 SN - 0008-5472, 0008-5472 KW - BMP4 protein, human KW - 0 KW - Bmp4 protein, mouse KW - Bone Morphogenetic Protein 4 KW - Bone Morphogenetic Proteins KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - BMPR2 protein, human KW - EC 2.7.11.30 KW - Bmpr2 protein, mouse KW - Bone Morphogenetic Protein Receptors, Type II KW - Index Medicus KW - Animals KW - Transfection KW - Bone Morphogenetic Proteins -- pharmacology KW - Humans KW - Cell Division -- physiology KW - Mice, Nude KW - Mice KW - Cell Line, Tumor KW - Signal Transduction KW - Male KW - Protein-Serine-Threonine Kinases -- biosynthesis KW - Carcinoma, Transitional Cell -- pathology KW - Urinary Bladder Neoplasms -- pathology KW - Urinary Bladder Neoplasms -- genetics KW - Carcinoma, Transitional Cell -- metabolism KW - Protein-Serine-Threonine Kinases -- genetics KW - Urinary Bladder Neoplasms -- metabolism KW - Carcinoma, Transitional Cell -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66983447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Restoration+of+bone+morphogenetic+protein+receptor+type+II+expression+leads+to+a+decreased+rate+of+tumor+growth+in+bladder+transitional+cell+carcinoma+cell+line+TSU-Pr1.&rft.au=Kim%2C+Isaac+Yi%3BLee%2C+Dong-Hyeon%3BLee%2C+Dug+Keun%3BKim%2C+Wun+Jae%3BKim%2C+Moses+M%3BMorton%2C+Ronald+A%3BLerner%2C+Seth+P%3BKim%2C+Seong+Jin&rft.aulast=Kim&rft.aufirst=Isaac&rft.date=2004-10-15&rft.volume=64&rft.issue=20&rft.spage=7355&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 - 2004-12-03 N1 - Date created - 2004-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sustained beta1-adrenergic stimulation modulates cardiac contractility by Ca2+/calmodulin kinase signaling pathway. AN - 66974520; 15375008 AB - A tenet of beta1-adrenergic receptor (beta1AR) signaling is that stimulation of the receptor activates the adenylate cyclase-cAMP-protein kinase A (PKA) pathway, resulting in positive inotropic and relaxant effects in the heart. However, recent studies have suggested the involvement of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in beta1AR-stimulated cardiac apoptosis. In this study, we determined roles of CaMKII and PKA in sustained versus short-term beta1AR modulation of excitation-contraction (E-C) coupling in cardiac myocytes. Short-term (10-minute) and sustained (24-hour) beta1AR stimulation with norepinephrine similarly enhanced cell contraction and Ca2+ transients, in contrast to anticipated receptor desensitization. More importantly, the sustained responses were largely PKA-independent, and were sensitive to specific CaMKII inhibitors or adenoviral expression of a dominant-negative CaMKII mutant. Biochemical assays revealed that a progressive and persistent CaMKII activation was associated with a rapid desensitization of the cAMP/PKA signaling. Concomitantly, phosphorylation of phospholamban, an SR Ca2+ cycling regulatory protein, was shifted from its PKA site (16Ser) to CaMKII site (17Thr). Thus, beta1AR stimulation activates dual signaling pathways mediated by cAMP/PKA and CaMKII, the former undergoing desensitization and the latter exhibiting sensitization. This finding may bear important etiological and therapeutical ramifications in understanding beta1AR signaling in chronic heart failure. JF - Circulation research AU - Wang, Wang AU - Zhu, Weizhong AU - Wang, Shiqiang AU - Yang, Dongmei AU - Crow, Michael T AU - Xiao, Rui-Ping AU - Cheng, Heping AD - Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 798 EP - 806 VL - 95 IS - 8 KW - Adrenergic alpha-Agonists KW - 0 KW - Calcium-Binding Proteins KW - Receptors, Adrenergic, beta-1 KW - Recombinant Fusion Proteins KW - phospholamban KW - Cyclic AMP KW - E0399OZS9N KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2 KW - EC 2.7.11.17 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - Norepinephrine KW - X4W3ENH1CV KW - Prazosin KW - XM03YJ541D KW - Index Medicus KW - Animals KW - Myocytes, Cardiac -- drug effects KW - Myocytes, Cardiac -- physiology KW - Adrenergic alpha-Agonists -- pharmacology KW - Norepinephrine -- pharmacology KW - Humans KW - Protein Processing, Post-Translational KW - Cells, Cultured -- drug effects KW - Recombinant Fusion Proteins -- physiology KW - Cell Size -- drug effects KW - Rats KW - Mutagenesis, Site-Directed KW - Rats, Sprague-Dawley KW - Phosphorylation KW - Prazosin -- pharmacology KW - Cells, Cultured -- physiology KW - Calcium-Binding Proteins -- metabolism KW - Male KW - Calcium-Calmodulin-Dependent Protein Kinases -- genetics KW - Receptors, Adrenergic, beta-1 -- physiology KW - Cyclic AMP-Dependent Protein Kinases -- physiology KW - Myocardial Contraction -- drug effects KW - Cyclic AMP -- physiology KW - Calcium Signaling -- drug effects KW - Second Messenger Systems -- physiology KW - Calcium Signaling -- physiology KW - Calcium-Calmodulin-Dependent Protein Kinases -- antagonists & inhibitors KW - Second Messenger Systems -- drug effects KW - Myocardial Contraction -- physiology KW - Calcium-Calmodulin-Dependent Protein Kinases -- physiology KW - Receptors, Adrenergic, beta-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66974520?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation+research&rft.atitle=Sustained+beta1-adrenergic+stimulation+modulates+cardiac+contractility+by+Ca2%2B%2Fcalmodulin+kinase+signaling+pathway.&rft.au=Wang%2C+Wang%3BZhu%2C+Weizhong%3BWang%2C+Shiqiang%3BYang%2C+Dongmei%3BCrow%2C+Michael+T%3BXiao%2C+Rui-Ping%3BCheng%2C+Heping&rft.aulast=Wang&rft.aufirst=Wang&rft.date=2004-10-15&rft.volume=95&rft.issue=8&rft.spage=798&rft.isbn=&rft.btitle=&rft.title=Circulation+research&rft.issn=1524-4571&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-28 N1 - Date created - 2004-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-term follow-up for locally advanced and inflammatory breast cancer patients treated with multimodality therapy. AN - 66971237; 15483018 AB - To determine long-term event-free (EFS) and overall survival (OS) for patients with stage III breast cancer treated with combined-modality therapy. Between 1980 and 1988, 107 patients with stage III breast cancer were prospectively enrolled for study at the National Cancer Institute and stratified by whether or not they had features of inflammatory breast cancer (IBC). Patients were treated to best response with cyclophosphamide, doxorubicin, methotrexate, fluorouracil, leucovorin, and hormonal synchronization with conjugated estrogens and tamoxifen. Patients with pathologic complete response received definitive radiotherapy to the breast and axilla, whereas patients with residual disease underwent mastectomy, lymph node dissection, and radiotherapy. All patients underwent six additional cycles of adjuvant chemotherapy. OS and EFS were obtained with a median live patient follow-up time of 16.8 years. The 46 IBC patients had a median OS of 3.8 years and EFS of 2.3 years, compared with 12.2 and 9.0 years, respectively, in stage IIIA breast cancer patients. Fifteen-year OS survival was 20% for IBC versus 50% for stage IIIA patients and 23% for stage IIIB non-IBC. Pathologic response was not associated with improved survival for stage IIIA or IBC patients. Presence of dermal lymphatic invasion did not change the probability of survival in clinical IBC patients. Fifteen-year follow-up of stage IIIA and inflammatory breast cancer is rarely reported; IBC patients have a poor long-term outlook. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Low, Jennifer A AU - Berman, Arlene W AU - Steinberg, Seth M AU - Danforth, David N AU - Lippman, Marc E AU - Swain, Sandra M AD - Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bldg 8, Rm 5101, 8901 Wisconsin Ave, Bethesda, MD 20889-5015, USA. Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 4067 EP - 4074 VL - 22 IS - 20 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Alkylating KW - 0 KW - Index Medicus KW - Disease-Free Survival KW - Survival Rate KW - Humans KW - Neoadjuvant Therapy KW - Adult KW - Aged KW - Middle Aged KW - Mastectomy KW - Follow-Up Studies KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Female KW - Inflammation KW - Breast Neoplasms -- mortality KW - Breast Neoplasms -- pathology KW - Combined Modality Therapy KW - Breast Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66971237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Long-term+follow-up+for+locally+advanced+and+inflammatory+breast+cancer+patients+treated+with+multimodality+therapy.&rft.au=Low%2C+Jennifer+A%3BBerman%2C+Arlene+W%3BSteinberg%2C+Seth+M%3BDanforth%2C+David+N%3BLippman%2C+Marc+E%3BSwain%2C+Sandra+M&rft.aulast=Low&rft.aufirst=Jennifer&rft.date=2004-10-15&rft.volume=22&rft.issue=20&rft.spage=4067&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 - 2004-11-04 N1 - Date created - 2004-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neurotoxicity of carbonyl sulfide in F344 rats following inhalation exposure for up to 12 weeks. AN - 66962564; 15476866 AB - Carbonyl sulfide (COS), a high-priority Clean Air Act chemical, was evaluated for neurotoxicity in short-term studies. F344 rats were exposed to 75-600 ppm COS 6 h per day, 5 days per week for up to 12 weeks. In rats exposed to 500 or 600 ppm for up to 4 days, malacia and microgliosis were detected in numerous neuroanatomical regions of the brain by conventional optical microscopy and magnetic resonance microscopy (MRM). After a 2-week exposure to 400 ppm, rats were evaluated using a functional observational battery. Slight gait abnormality was detected in 50% of the rats and hypotonia was present in all rats exposed to COS. Decreases in motor activity, and forelimb and hindlimb grip strength were also detected. In rats exposed to 400 ppm for 12 weeks, predominant lesions were in the parietal cortex area 1 (necrosis) and posterior colliculus (neuronal loss, microgliosis, hemorrhage), and occasional necrosis was present in the putamen, thalamus, and anterior olivary nucleus. Carbonyl sulfide specifically targeted the auditory system including the olivary nucleus, nucleus of the lateral lemniscus, and posterior colliculus. Consistent with these findings were alterations in the amplitude of the brainstem auditory evoked responses (BAER) for peaks N3, P4, N4, and N5 that represented changes in auditory transmission between the anterior olivary nucleus to the medial geniculate nucleus in animals after exposure for 2 weeks to 400 ppm COS. A concentration-related decrease in cytochrome oxidase activity was detected in the posterior colliculus and parietal cortex of exposed rats as early as 3 weeks. Cytochrome oxidase activity was significantly decreased at COS concentrations that did not cause detectable lesions, suggesting that disruption of the mitochondrial respiratory chain may precede these brain lesions. Our studies demonstrate that this environmental air contaminant has the potential to cause a wide spectrum of brain lesions that are dependent on the degree and duration of exposure. JF - Toxicology and applied pharmacology AU - Morgan, Daniel L AU - Little, Peter B AU - Herr, David W AU - Moser, Virginia C AU - Collins, Bradley AU - Herbert, Ronald AU - Johnson, G Allan AU - Maronpot, Robert R AU - Harry, G Jean AU - Sills, Robert C AD - Laboratory of Molecular Toxicology, NIEHS, Research Triangle Park, NC 27709, USA. Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 131 EP - 145 VL - 200 IS - 2 SN - 0041-008X, 0041-008X KW - Air Pollutants KW - 0 KW - Neurotoxins KW - Sulfur Oxides KW - carbonyl sulfide KW - 871UI0ET21 KW - Electron Transport Complex IV KW - EC 1.9.3.1 KW - Index Medicus KW - Animals KW - Blood Chemical Analysis KW - Random Allocation KW - Histocytochemistry KW - Rats KW - Behavior, Animal -- drug effects KW - Rats, Inbred F344 KW - Electron Transport Complex IV -- analysis KW - Inhalation Exposure KW - Evoked Potentials, Auditory, Brain Stem -- drug effects KW - Motor Activity -- drug effects KW - Female KW - Male KW - Brain Diseases -- chemically induced KW - Brain Diseases -- pathology KW - Sulfur Oxides -- toxicity KW - Air Pollutants -- toxicity KW - Neurotoxins -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66962564?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Neurotoxicity+of+carbonyl+sulfide+in+F344+rats+following+inhalation+exposure+for+up+to+12+weeks.&rft.au=Morgan%2C+Daniel+L%3BLittle%2C+Peter+B%3BHerr%2C+David+W%3BMoser%2C+Virginia+C%3BCollins%2C+Bradley%3BHerbert%2C+Ronald%3BJohnson%2C+G+Allan%3BMaronpot%2C+Robert+R%3BHarry%2C+G+Jean%3BSills%2C+Robert+C&rft.aulast=Morgan&rft.aufirst=Daniel&rft.date=2004-10-15&rft.volume=200&rft.issue=2&rft.spage=131&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 - 2004-11-23 N1 - Date created - 2004-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterizing complex peptide mixtures using a multi-dimensional liquid chromatography-mass spectrometry system: Saccharomyces cerevisiae as a model system. AN - 66860767; 15358309 AB - A rugged, reproducible, multi-dimensional LC-MS system was developed to identify and characterize proteins involved in protein-protein interactions and/or protein complexes. Our objective was to optimize chromatographic parameters for complex protein mixture analyses using automated peptide sequence recognition as an analytical end-point. The chromatographic system uses orthogonal separation mechanisms by employing strong cation exchange (SCX) in the first dimension and reversed phase (RP) in the second dimension. The system is fully automated and sufficiently robust to handle direct injections of protein digests. This system incorporates a streamlined post analysis results comparison, called DBParser, which permitted comprehensive evaluation of sample loading and chromatographic conditions to optimize the performance and reproducibility. Peptides obtained from trypsin digestion of a yeast soluble extract provided an open-ended model system containing a wide variety and dynamic range of components. Conditions are described that resulted in an average (n = 4) of 1489 unique peptide identifications, corresponding to 459 non-redundant protein sequence database records (SDRs) in the 20 microg soluble fraction digest. JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences AU - Maynard, Dawn M AU - Masuda, Junichi AU - Yang, Xiaoyu AU - Kowalak, Jeffrey A AU - Markey, Sanford P AD - Laboratory of Neurotoxicology, National Institute of Mental Health, NIH, Bethesda, MD 20892-1262, USA. maynardd@mail.nih.gov Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 69 EP - 76 VL - 810 IS - 1 SN - 1570-0232, 1570-0232 KW - Indicators and Reagents KW - 0 KW - Peptides KW - Protein Hydrolysates KW - Trypsin KW - EC 3.4.21.4 KW - Index Medicus KW - Trypsin -- chemistry KW - Spectrometry, Mass, Electrospray Ionization KW - Protein Hydrolysates -- analysis KW - Chromatography, Liquid KW - Databases, Genetic KW - Saccharomyces cerevisiae -- growth & development KW - Peptides -- analysis KW - Saccharomyces cerevisiae -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66860767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Characterizing+complex+peptide+mixtures+using+a+multi-dimensional+liquid+chromatography-mass+spectrometry+system%3A+Saccharomyces+cerevisiae+as+a+model+system.&rft.au=Maynard%2C+Dawn+M%3BMasuda%2C+Junichi%3BYang%2C+Xiaoyu%3BKowalak%2C+Jeffrey+A%3BMarkey%2C+Sanford+P&rft.aulast=Maynard&rft.aufirst=Dawn&rft.date=2004-10-15&rft.volume=810&rft.issue=1&rft.spage=69&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 - 2005-02-25 N1 - Date created - 2004-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic Analysis Reveals that Thyroid Hormone Receptor Is Sufficient To Mediate the Thyroid Hormone Signal in Frog Metamorphosis AN - 19815719; 6043353 AB - Thyroid hormone (T3) has long been known to be important for vertebrate development and adult organ function. Whereas thyroid hormone receptor (TR) knockout and transgenic studies of mice have implicated TR involvement in mammalian development, the underlying molecular bases for the resulting phenotypes remain to be determined in vivo, especially considering that T3 is known to have both genomic, i.e., through TRs, and nongenomic effects on cells. Amphibian metamorphosis is an excellent model for studying the role of TR in vertebrate development because of its total dependence on T3. Here we investigated the role of TR in metamorphosis by developing a dominant positive mutant thyroid hormone receptor (dpTR). In the frog oocyte transcription system, dpTR bound a T3-responsive promoter and activated the promoter independently of T3. Transgenic expression of dpTR under the control of a heat shock-inducible promoter in premetamorphic tadpoles led to precocious metamorphic transformations. Molecular analyses showed that dpTR induced metamorphosis by specifically binding to known T3 target genes, leading to increased local histone acetylation and gene activation, similar to T3-bound TR during natural metamorphosis. Our experiments indicated that the metamorphic role of T3 is through genomic action of the hormone, at least on the developmental parameters tested. They further provide the first example where TR is shown to mediate directly and sufficiently these developmental effects of T3 in individual organs by regulating target gene expression in these organs. JF - Molecular and Cellular Biology AU - Buchholz, Daniel R AU - Tomita, Akihiro AU - Fu, Liezhen AU - Paul, Bindu D AU - Shi, Yun-Bo AD - Section on Molecular Morphogenesis, Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 9026 EP - 9037 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA VL - 24 IS - 20 SN - 0270-7306, 0270-7306 KW - True frogs KW - Biotechnology and Bioengineering Abstracts; ASFA 1: Biological Sciences & Living Resources; Genetics Abstracts KW - Transformation KW - Histones KW - Amphibiotic species KW - Life cycle KW - Rana KW - Hormones KW - Thyroid hormones KW - Promoters KW - Thyroid hormone receptors KW - Heat shock KW - Oocytes KW - Metamorphosis KW - genomics KW - Cell fate KW - Biological development KW - Developmental genetics KW - Anura KW - Thyroid KW - Receptors KW - Transcription KW - Triiodothyronine KW - Transgenic mice KW - Acetylation KW - Heat KW - Transcription factors KW - Gene regulation KW - Pattern formation KW - Transcription activation KW - W 30925:Genetic Engineering KW - G 07373:Amphibians KW - Q1 08375:Genetics and evolution KW - G 07250:Developmental genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19815719?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+and+Cellular+Biology&rft.atitle=Transgenic+Analysis+Reveals+that+Thyroid+Hormone+Receptor+Is+Sufficient+To+Mediate+the+Thyroid+Hormone+Signal+in+Frog+Metamorphosis&rft.au=Buchholz%2C+Daniel+R%3BTomita%2C+Akihiro%3BFu%2C+Liezhen%3BPaul%2C+Bindu+D%3BShi%2C+Yun-Bo&rft.aulast=Buchholz&rft.aufirst=Daniel&rft.date=2004-10-15&rft.volume=24&rft.issue=20&rft.spage=9026&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 revised - 2007-01-01 N1 - Last updated - 2016-05-27 N1 - SubjectsTermNotLitGenreText - Promoters; Biological development; Histones; Amphibiotic species; Receptors; Thyroid; Life cycle; Metamorphosis; Hormones; Transformation; Developmental genetics; Transcription; Triiodothyronine; Transgenic mice; Acetylation; Thyroid hormones; Thyroid hormone receptors; Heat; Gene regulation; Transcription factors; Oocytes; Heat shock; Cell fate; genomics; Transcription activation; Pattern formation; Anura; Rana ER - TY - JOUR T1 - GadY, a Small-RNA Regulator of Acid Response Genes in Escherichia coli AN - 18060999; 6041678 AB - A previous bioinformatics-based search for small RNAs in Escherichia coli identified a novel RNA named IS183. The gene encoding this small RNA is located between and on the opposite strand of genes encoding two transcriptional regulators of the acid response, gadX (yhiX) and gadW (yhiW). Given that IS183 is encoded in the gad gene cluster and because of its role in regulating acid response genes reported here, this RNA has been renamed GadY. We show that GadY exists in three forms, a long form consisting of 105 nucleotides and two processed forms, consisting of 90 and 59 nucleotides. The expression of this small RNA is highly induced during stationary phase in a manner that is dependent on the alternative sigma factor capital sigma super(S). Overexpression of the three GadY RNA forms resulted in increased levels of the mRNA encoding the GadX transcriptional activator, which in turn caused increased levels of the GadA and GadB glutamate decarboxylases. A promoter mutation which abolished gadY expression resulted in a reduction in the amount of gadX mRNA during stationary phase. The gadY gene was shown to overlap the 3' end of the gadX gene, and this overlap region was found to be necessary for the GadY-dependent accumulation of gadX mRNA. We suggest that during stationary phase, GadY forms base pairs with the 3'-untranslated region of the gadX mRNA and confers increased stability, allowing for gadX mRNA accumulation and the increased expression of downstream acid resistance genes. JF - Journal of Bacteriology AU - Opdyke, Jason A AU - Kang, Ju-Gyeong AU - Storz, Gisela AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 6698 EP - 6705 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 186 IS - 20 SN - 0021-9193, 0021-9193 KW - gadW gene KW - gadX gene KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - s factor KW - mRNA stability KW - ^s factor KW - RNA KW - S phase KW - Acids KW - Gene clusters KW - Transcription activators KW - Escherichia coli KW - Bioinformatics KW - Glutamate decarboxylase KW - J 02726:RNA and ribosomes KW - G 07320:Bacterial genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18060999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=GadY%2C+a+Small-RNA+Regulator+of+Acid+Response+Genes+in+Escherichia+coli&rft.au=Opdyke%2C+Jason+A%3BKang%2C+Ju-Gyeong%3BStorz%2C+Gisela&rft.aulast=Opdyke&rft.aufirst=Jason&rft.date=2004-10-15&rft.volume=186&rft.issue=20&rft.spage=6698&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Bioinformatics; RNA; Gene clusters; S phase; s factor; mRNA stability; Transcription activators; Glutamate decarboxylase; Acids; ^s factor ER - TY - JOUR T1 - Chemical Structure, Conjugation, and Cross-Reactivity of Bacillus pumilus Sh18 Cell Wall Polysaccharide AN - 18060710; 6041701 AB - Bacillus pumilus strain Sh18 cell wall polysaccharide (CWP), cross-reactive with the capsular polysaccharide of Haemophilus influenzae type b, was purified and its chemical structure was elucidated using fast atom bombardment mass spectrometry, nuclear magnetic resonance techniques, and sugar-specific degradation procedures. Two major structures, 1,5-poly(ribitol phosphate) and 1,3-poly(glycerol phosphate), with the latter partially substituted by 2- acetamido-2-deoxy- alpha -galactopyranose (13%) and 2-acetamido-2-deoxy- alpha - glucopyranose (6%) on position O-2, were found. A minor component was established to be a polymer of right arrow3-O-(2-acetamido-2-deoxy-beta- glucopyranosyl)-1right arrow4-ribitol-1-OPO sub(3)right arrow. The ratios of the three components were 56, 34, and 10 mol%, respectively. The Sh18 CWP was covalently bound to carrier proteins, and the immunogenicity of the resulting conjugates was evaluated in mice. Two methods of conjugation were compared: (i) binding of 1-cyano-4-dimethylaminopyridinium tetrafluoroborate-activated hydroxyl groups of the CWP to adipic acid dihydrazide (ADH)-derivatized protein, and (ii) binding of the carbodiimide-activated terminal phosphate group of the CWP to ADH-derivatized protein. The conjugate-induced antibodies reacted in an enzyme-linked immunosorbent assay with the homologous polysaccharide and with a number of other bacterial polysaccharides containing ribitol and glycerol phosphates, including H. influenzae types a and b and strains of Staphylococcus aureus and Staphylococcus epidermidis. JF - Journal of Bacteriology AU - Kubler-Kielb, Joanna AU - Coxon, Bruce AU - Schneerson, Rachel AD - Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 6891 EP - 6901 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 186 IS - 20 SN - 0021-9193, 0021-9193 KW - 1,5-poly(ribitol phosphate) KW - Microbiology Abstracts B: Bacteriology KW - Enzyme-linked immunosorbent assay KW - Biodegradation KW - Cross-reactivity KW - Haemophilus influenzae KW - Adipic acid dihydrazide KW - Polysaccharides KW - Antibodies KW - Glycerol KW - Phosphate KW - Immunogenicity KW - N.M.R. KW - Polymers KW - Staphylococcus aureus KW - Staphylococcus epidermidis KW - Cell walls KW - Bacillus pumilus KW - J 02730:Carbohydrates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18060710?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemical+Structure%2C+Conjugation%2C+and+Cross-Reactivity+of+Bacillus+pumilus+Sh18+Cell+Wall+Polysaccharide&rft.au=Kubler-Kielb%2C+Joanna%3BCoxon%2C+Bruce%3BSchneerson%2C+Rachel&rft.aulast=Kubler-Kielb&rft.aufirst=Joanna&rft.date=2004-10-15&rft.volume=186&rft.issue=20&rft.spage=6891&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus pumilus; Haemophilus influenzae; Staphylococcus aureus; Staphylococcus epidermidis; Polysaccharides; Phosphate; Cell walls; Cross-reactivity; Adipic acid dihydrazide; N.M.R.; Biodegradation; Immunogenicity; Polymers; Glycerol; Antibodies; Enzyme-linked immunosorbent assay ER - TY - JOUR T1 - Increased Colonization of Indwelling Medical Devices by Quorum-Sensing Mutants of Staphylococcus epidermidis In Vivo AN - 17729061; 6068255 AB - Infections with the leading nosocomial pathogen Staphylococcus epidermidis are characterized by biofilm development on indwelling medical devices. We demonstrate that the quorum-sensing regulator agr affects the biofilm development of S. epidermidis in an unexpected fashion and is likely involved in promoting biofilm detachment. An isogenic agr mutant showed increased biofilm development and colonization in a rabbit model. In addition, nonfunctional agr occurred more frequently among strains isolated from infections of joint prostheses. Lack of functionality was based on mutations, including insertion of an IS256 element. Relative to other bacterial pathogens, quorum sensing in S. epidermidis thus has a different role during biofilm development and biofilm-associated infection. Our results indicate that disabling agr likely enhances the success of S. epidermidis during infection of indwelling medical devices. The permanent elimination of quorum-sensing regulation used by S. epidermidis represents a surprising and unusual means to adapt to a certain environment and type of infection. JF - Journal of Infectious Diseases AU - Vuong, C AU - Kocianova, S AU - Yao, Y AU - Carmody, AB AU - Otto, M AD - Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 1498 EP - 1505 VL - 190 IS - 8 SN - 0022-1899, 0022-1899 KW - rabbits KW - Microbiology Abstracts B: Bacteriology; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Colonization KW - Adaptations KW - quorum sensing KW - Animal models KW - Biofilms KW - Development KW - Infection KW - Insertion sequences KW - Staphylococcus epidermidis KW - Joints KW - Prosthetics KW - A 01110:Environmental KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17729061?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Increased+Colonization+of+Indwelling+Medical+Devices+by+Quorum-Sensing+Mutants+of+Staphylococcus+epidermidis+In+Vivo&rft.au=Vuong%2C+C%3BKocianova%2C+S%3BYao%2C+Y%3BCarmody%2C+AB%3BOtto%2C+M&rft.aulast=Vuong&rft.aufirst=C&rft.date=2004-10-15&rft.volume=190&rft.issue=8&rft.spage=1498&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 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Colonization; Adaptations; quorum sensing; Animal models; Development; Biofilms; Insertion sequences; Infection; Prosthetics; Joints; Staphylococcus epidermidis ER - TY - JOUR T1 - MicC, a Second Small-RNA Regulator of Omp Protein Expression in Escherichia coli AN - 17696184; 6041677 AB - In a previous bioinformatics-based search for novel small-RNA genes encoded by the Escherichia coli genome, we identified a region, IS063, located between the ompN and ydbK genes, that encodes an -100-nucleotide small-RNA transcript. Here we show that the expression of this small RNA is increased at a low temperature and in minimal medium. Twenty-two nucleotides at the 5' end of this transcript have the potential to form base pairs with the leader sequence of the mRNA encoding the outer membrane protein OmpC. The deletion of IS063 increased the expression of an ompC-luc translational fusion 1.5- to 2-fold, and a 10-fold overexpression of the small RNA led to a 2- to 3-fold repression of the fusion. Deletion and overexpression of the IS063 RNA also resulted in increases and decreases, respectively, in OmpC protein levels. Taken together, these results suggest that IS063 is a regulator of OmpC expression; thus, the small RNA has been renamed MicC. The antisense regulation was further demonstrated by the finding that micC mutations were suppressed by compensatory mutations in the ompC mRNA. MicC was also shown to inhibit ribosome binding to the ompC mRNA leader in vitro and to require the Hfq RNA chaperone for its function. We suggest that the MicF and MicC RNAs act in conjunction with the EnvZ-OmpR two- component system to control the OmpF/OmpC protein ratio in response to a variety of environmental stimuli. JF - Journal of Bacteriology AU - Chen, Shuo AU - Zhang, Aixia AU - Blyn, Lawrence B AU - Storz, Gisela AD - IBIS Therapeutics, ISIS Pharmaceuticals, Inc., Carlsbad, California. Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland Y1 - 2004/10/15/ PY - 2004 DA - 2004 Oct 15 SP - 6689 EP - 6697 PB - American Society for Microbiology, 1752 N Street N.W. Washington, DC 20036 USA, [URL:http://www.asm.org/] VL - 186 IS - 20 SN - 0021-9193, 0021-9193 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids; Genetics Abstracts KW - Genomes KW - Translation KW - outer membrane proteins KW - Nucleotide sequence KW - Antisense KW - Escherichia coli KW - OmpC protein KW - Temperature effects KW - Deletion KW - 5' Untranslated regions KW - Transcription KW - Ribosomes KW - mRNA KW - OmpF protein KW - EnvZ protein KW - RNA KW - Overexpression KW - Chaperones KW - Mutation KW - J 02726:RNA and ribosomes KW - G 07320:Bacterial genetics KW - N 14070:Ribosomes: rRNA, ribosomal proteins, and translation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17696184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=MicC%2C+a+Second+Small-RNA+Regulator+of+Omp+Protein+Expression+in+Escherichia+coli&rft.au=Chen%2C+Shuo%3BZhang%2C+Aixia%3BBlyn%2C+Lawrence+B%3BStorz%2C+Gisela&rft.aulast=Chen&rft.aufirst=Shuo&rft.date=2004-10-15&rft.volume=186&rft.issue=20&rft.spage=6689&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Temperature effects; OmpC protein; OmpF protein; EnvZ protein; Antisense; Overexpression; Deletion; RNA; mRNA; Mutation; Transcription; Genomes; Chaperones; Ribosomes; outer membrane proteins; Translation; 5' Untranslated regions; Nucleotide sequence ER - TY - JOUR T1 - Intrastriatal transforming growth factor alpha delivery to a model of Parkinson's disease induces proliferation and migration of endogenous adult neural progenitor cells without differentiation into dopaminergic neurons. AN - 66975192; 15483111 AB - We examined the cell proliferative, neurogenic, and behavioral effects of transforming growth factor alpha (TGFalpha) in a 6-OHDA Parkinson's disease model when compared with naive rats. Intrastriatal TGFalpha infusion induced significant proliferation, hyperplastic nodules, and substantial migratory waves of nestin-positive progenitor cells from the adult subventricular zone (SVZ) of dopamine-denervated rats. Interestingly, SVZ cells in naive rats displayed proliferation but minimal migration in response to the TGFalpha infusion. The cells in the expanded SVZ accumulated cytoplasmic beta-catenin, indicating activation of classical Wnt signaling. However, no evidence of any neuronal differentiation was found of these recruited progenitor cells anywhere examined in the brain. Consequently, no evidence of dopaminergic (DA) neurogenesis was found in the striatum or substantia nigra in any experimental group, and amphetamine-induced behavioral rotations did not improve. In summary, the cells in the TGFalpha-induced migratory cellular wave remain undifferentiated and do not differentiate into midbrain-like DA neurons. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Cooper, Oliver AU - Isacson, Ole AD - Harvard University and McLean Hospital, National Institute of Neurological Disorders and Stroke Udall Parkinson's Disease Research Center of Excellence, Belmont, Massachusetts 02478, USA. Y1 - 2004/10/13/ PY - 2004 DA - 2004 Oct 13 SP - 8924 EP - 8931 VL - 24 IS - 41 KW - Ctnnb1 protein, rat KW - 0 KW - Cytoskeletal Proteins KW - Intermediate Filament Proteins KW - Nerve Tissue Proteins KW - Nes protein, rat KW - Nestin KW - Trans-Activators KW - Transforming Growth Factor alpha KW - beta Catenin KW - Oxidopamine KW - 8HW4YBZ748 KW - Tyrosine 3-Monooxygenase KW - EC 1.14.16.2 KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Cell Proliferation -- drug effects KW - Trans-Activators -- metabolism KW - Animals KW - Disease Models, Animal KW - Dopamine -- metabolism KW - Tyrosine 3-Monooxygenase -- biosynthesis KW - Nerve Tissue Proteins -- biosynthesis KW - Lateral Ventricles -- drug effects KW - Lateral Ventricles -- metabolism KW - Lateral Ventricles -- cytology KW - Drug Administration Routes KW - Rats KW - Behavior, Animal -- drug effects KW - Rats, Sprague-Dawley KW - Intermediate Filament Proteins -- biosynthesis KW - Cytoskeletal Proteins -- metabolism KW - Male KW - Stem Cells -- drug effects KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Parkinsonian Disorders -- chemically induced KW - Transforming Growth Factor alpha -- administration & dosage KW - Cell Movement -- drug effects KW - Stem Cells -- pathology KW - Corpus Striatum -- drug effects KW - Corpus Striatum -- pathology KW - Parkinsonian Disorders -- drug therapy KW - Parkinsonian Disorders -- pathology KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66975192?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Intrastriatal+transforming+growth+factor+alpha+delivery+to+a+model+of+Parkinson%27s+disease+induces+proliferation+and+migration+of+endogenous+adult+neural+progenitor+cells+without+differentiation+into+dopaminergic+neurons.&rft.au=Cooper%2C+Oliver%3BIsacson%2C+Ole&rft.aulast=Cooper&rft.aufirst=Oliver&rft.date=2004-10-13&rft.volume=24&rft.issue=41&rft.spage=8924&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 - 2005-01-12 N1 - Date created - 2004-10-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Neurosci. 2000 Nov;3(11):1091-7 [11036265] Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13883-8 [11095732] Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14686-91 [11121069] Neuron. 2000 Dec;28(3):713-26 [11163261] Nat Rev Neurosci. 2001 Apr;2(4):287-93 [11283751] Curr Opin Genet Dev. 2001 Oct;11(5):547-53 [11532397] Brain Res Bull. 2001 Jul 1;55(4):541-8 [11543955] Development. 2001 Nov;128(21):4203-16 [11684657] Exp Neurol. 2001 Dec;172(2):363-76 [11716560] Science. 2001 Dec 7;294(5549):2127-30 [11739948] J Neurosci. 2002 Feb 1;22(3):614-8 [11826088] Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2344-9 [11782534] Brain Res Dev Brain Res. 2002 Mar 31;134(1-2):13-21 [11947933] Histochem Cell Biol. 2002 Jun;117(6):535-40 [12107504] J Neurosci Res. 2002 Sep 15;69(6):763-71 [12205670] Clin Cancer Res. 2002 Oct;8(10):3054-64 [12374672] Neuron. 2002 Dec 19;36(6):1021-34 [12495619] J Neurosci. 2003 Apr 1;23(7):2840-50 [12684471] J Comp Neurol. 2003 Jun 9;460(4):563-72 [12717714] Glia. 2003 Jul;43(1):19-32 [12761862] Dev Biol. 2003 Jun 15;258(2):406-18 [12798297] Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7925-30 [12792021] J Comp Neurol. 2003 Dec 1;467(1):1-10 [14574675] Brain Res. 2003 Dec 19;994(1):81-90 [14642451] Nature. 2004 Feb 19;427(6976):740-4 [14973487] J Neurosci. 2004 Mar 3;24(9):2133-42 [14999064] Science. 2004 Mar 5;303(5663):1483-7 [15001769] Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10177-82 [15210991] J Pharmacol Exp Ther. 1979 Feb;208(2):203-9 [762652] Proc Natl Acad Sci U S A. 1980 Sep;77(9):5258-62 [6254071] N Engl J Med. 1988 Sep 1;319(9):525-32 [2841597] Exp Brain Res. 1988;71(2):411-24 [2901978] Cell. 1990 Feb 23;60(4):585-95 [1689217] Science. 1991 Nov 29;254(5036):1359-61 [1962194] Science. 1992 Mar 27;255(5052):1707-10 [1553558] Brain Res. 1995 Jan 23;670(1):157-64 [7719717] J Neurosci. 1996 Apr 15;16(8):2649-58 [8786441] J Neurosci. 1997 May 1;17(9):3254-61 [9096158] J Comp Neurol. 1997 Apr 7;380(2):243-61 [9100135] Neuron. 1997 May;18(5):779-91 [9182802] J Neurosci. 1997 Aug 1;17(15):5820-9 [9221780] J Neurosci. 1997 Oct 15;17(20):7850-9 [9315905] Exp Neurol. 1997 Nov;148(1):388-92 [9398481] J Neurobiol. 1998 Aug;36(2):287-306 [9712310] J Comp Neurol. 1999 Mar 22;405(4):508-28 [10098942] Nat Neurosci. 1998 Sep;1(5):374-7 [10196526] Cell. 1999 Jun 11;97(6):703-16 [10380923] J Neurosci. 1999 Jul 15;19(14):6006-16 [10407038] Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11619-24 [10500226] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A 4'-C-ethynyl-2',3'-dideoxynucleoside analogue highlights the role of the 3'-OH in anti-HIV active 4'-C-ethynyl-2'-deoxy nucleosides. AN - 66930187; 15456247 AB - 4'-C-ethynyl-2'-deoxynucleosides belong to a novel class of nucleoside analogues endowed with potent activity against a wide spectrum of HIV viruses, including a variety of resistant clones. Although favorable selectivity indices were reported for several of these analogues, some concern still exists regarding the 3'-OH group and its role in cellular toxicity. To address this problem, we removed the 3'-OH group from 4'-C-ethynyl-2'-deoxycytidine (1a). This compound was chosen because of its combined high potency and low selectivity index. The removal of the 3'-OH was not straightforward; it required a different synthetic approach from the one used to synthesize the parent compound. Starting with glycidyl-4-methoxyphenyl ether, the target 4'-C-ethynyl-2',3'-dideoxycytidine analogue (rac-1h) was obtained after 13 steps. In a cellular assay, rac-1h was completely inactive (0.001-10 microM) against HIV(LAI), demonstrating the critical importance of the 3'-OH for antiviral activity. To determine whether the role of the 3'-OH was essential for the phosphorylation of the compound by cellular kinases or for inhibition of DNA polymerization, we synthesized and tested the 5'-triphosphate (rac-1h-TP) for its ability to inhibit HIV reverse transcriptase (RT). rac-1h-TP was slightly more potent than AZT-5'-triphosphate against wild-type HIV RT, suggesting that the role of the 3'-OH is crucial only for the activation of the drug by cellular kinases. The lipase-catalyzed resolution of rac-1h into ent-1h (beta-D-dideoxyribo) and ent-14 (beta-L-dideoxyribo) and the synthesis of the corresponding 5'-triphosphates established the stereochemical assignment based on HIV RT's preference for the beta-D-enantiomer, which was confirmed by assaying against the M184V variant, an RT mutant with a marked preference for incorporating nucleosides in the D-configuration. JF - Journal of medicinal chemistry AU - Siddiqui, Maqbool A AU - Hughes, Stephen H AU - Boyer, Paul L AU - Mitsuya, Hiroaki AU - Van, Que N AU - George, Clifford AU - Sarafinanos, Stefan G AU - Marquez, Victor E AD - Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute-Frederick, NIH, Frederick, MD 21702, USA. Y1 - 2004/10/07/ PY - 2004 DA - 2004 Oct 07 SP - 5041 EP - 5048 VL - 47 IS - 21 SN - 0022-2623, 0022-2623 KW - 6-amino-3-(5-ethynyl-5-(hydroxymethyl)oxolan-2-yl)-3-hydroxypyrimidin-2-one KW - 0 KW - Alkynes KW - Anti-HIV Agents KW - DNA, Viral KW - Dideoxynucleosides KW - Organophosphates KW - Prodrugs KW - Zalcitabine KW - 6L3XT8CB3I KW - Phosphotransferases KW - EC 2.7.- KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Index Medicus KW - Molecular Structure KW - HIV-1 -- genetics KW - Stereoisomerism KW - Prodrugs -- chemistry KW - Organophosphates -- chemical synthesis KW - Models, Molecular KW - Humans KW - HIV Reverse Transcriptase -- antagonists & inhibitors KW - HIV Reverse Transcriptase -- chemistry KW - Structure-Activity Relationship KW - Prodrugs -- chemical synthesis KW - Binding Sites KW - Organophosphates -- pharmacology KW - DNA, Viral -- chemistry KW - Phosphorylation KW - Organophosphates -- chemistry KW - Prodrugs -- pharmacology KW - Crystallography, X-Ray KW - HIV-1 -- drug effects KW - Cell Line KW - Phosphotransferases -- chemistry KW - Anti-HIV Agents -- chemistry KW - Dideoxynucleosides -- chemical synthesis KW - Alkynes -- chemical synthesis KW - Dideoxynucleosides -- chemistry KW - Alkynes -- pharmacology KW - Zalcitabine -- chemistry KW - Anti-HIV Agents -- chemical synthesis KW - Dideoxynucleosides -- pharmacology KW - Anti-HIV Agents -- pharmacology KW - Zalcitabine -- pharmacology KW - Alkynes -- chemistry KW - Zalcitabine -- analogs & derivatives KW - Zalcitabine -- chemical synthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66930187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+4%27-C-ethynyl-2%27%2C3%27-dideoxynucleoside+analogue+highlights+the+role+of+the+3%27-OH+in+anti-HIV+active+4%27-C-ethynyl-2%27-deoxy+nucleosides.&rft.au=Siddiqui%2C+Maqbool+A%3BHughes%2C+Stephen+H%3BBoyer%2C+Paul+L%3BMitsuya%2C+Hiroaki%3BVan%2C+Que+N%3BGeorge%2C+Clifford%3BSarafinanos%2C+Stefan+G%3BMarquez%2C+Victor+E&rft.aulast=Siddiqui&rft.aufirst=Maqbool&rft.date=2004-10-07&rft.volume=47&rft.issue=21&rft.spage=5041&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 - 2004-11-10 N1 - Date created - 2004-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synthesis and Potent Antitumor Activities of Novel 1,3,5-cis,cis- Triaminocyclohexane N-Pyridyl Derivatives AN - 19385320; 7151002 AB - The iron chelator N,N,N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (tachpyr) was recently reported to display potent antitumor activity. The present study was focused on identifying an adequate bifunctional version of tachpyr as a lead compound for use in antibody-targeted iron depletion tumor therapy. Preparation of tachpyr derivatives having a side chain is reported, and their cytotoxic activity is evaluated in the HeLa cell line. The observed cytotoxity appears dependent on the functionalization site of the tachpyr employed for introducing the protein conjugation. Tachpyr derivatives 14 and 15 having a side chain introduced into the 5-position of the pyridyl ring display more potent cytotoxicity than tachpyr derivatives 7 and 8 having a side chain introduced onto one of the secondary amines. BOC-protected tachpyr derivative 14 exhibited the most potent cytotoxicity against this cancer cell line, which was reasonably comparable to the parent tachpyr. Tachpyr derivative 14 was further converted into bifunctional tachpyr 17 possessing a maleimide linker for conjugation with thiolated monoclonal antibodies (mAbs). JF - Journal of Medicinal Chemistry AU - Chong, H-S AU - Torti, S V AU - Ma, R AU - Torti, F M AU - Brechbiel, M W AD - Chemistry Section, National Cancer Institute, NIH, Bethesda, Maryland, USA Y1 - 2004/10/07/ PY - 2004 DA - 2004 Oct 07 SP - 5230 EP - 5234 VL - 47 IS - 21 SN - 0022-2623, 0022-2623 KW - Biotechnology and Bioengineering Abstracts KW - amines KW - Tumor cell lines KW - Cytotoxicity KW - Monoclonal antibodies KW - Tumors KW - Chelating agents KW - Iron KW - Cancer KW - Antitumor activity KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19385320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Medicinal+Chemistry&rft.atitle=Synthesis+and+Potent+Antitumor+Activities+of+Novel+1%2C3%2C5-cis%2Ccis-+Triaminocyclohexane+N-Pyridyl+Derivatives&rft.au=Chong%2C+H-S%3BTorti%2C+S+V%3BMa%2C+R%3BTorti%2C+F+M%3BBrechbiel%2C+M+W&rft.aulast=Chong&rft.aufirst=H-S&rft.date=2004-10-07&rft.volume=47&rft.issue=21&rft.spage=5230&rft.isbn=&rft.btitle=&rft.title=Journal+of+Medicinal+Chemistry&rft.issn=00222623&rft_id=info:doi/10.102l%2Fjm040076w LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-12-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cytotoxicity; Antitumor activity; Iron; Monoclonal antibodies; Tumor cell lines; Chelating agents; Cancer; Tumors; amines DO - http://dx.doi.org/10.102l/jm040076w ER - TY - JOUR T1 - Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. AN - 66934440; 15451779 AB - Endocannabinoids are novel lipid mediators with hypotensive and cardiodepressor activity. Here, we examined the possible role of the endocannabinergic system in cardiovascular regulation in hypertension. In spontaneously hypertensive rats (SHR), cannabinoid-1 receptor (CB1) antagonists increase blood pressure and left ventricular contractile performance. Conversely, preventing the degradation of the endocannabinoid anandamide by an inhibitor of fatty acid amidohydrolase reduces blood pressure, cardiac contractility, and vascular resistance to levels in normotensive rats, and these effects are prevented by CB1 antagonists. Similar changes are observed in 2 additional models of hypertension, whereas in normotensive control rats, the same parameters remain unaffected by any of these treatments. CB1 agonists lower blood pressure much more in SHR than in normotensive Wistar-Kyoto rats, and the expression of CB1 is increased in heart and aortic endothelium of SHR compared with Wistar-Kyoto rats. We conclude that endocannabinoids tonically suppress cardiac contractility in hypertension and that enhancing the CB1-mediated cardiodepressor and vasodilator effects of endogenous anandamide by blocking its hydrolysis can normalize blood pressure. Targeting the endocannabinoid system offers novel therapeutic strategies in the treatment of hypertension. JF - Circulation AU - Bátkai, Sándor AU - Pacher, Pál AU - Osei-Hyiaman, Douglas AU - Radaeva, Svetlana AU - Liu, Jie AU - Harvey-White, Judith AU - Offertáler, László AU - Mackie, Ken AU - Rudd, M Audrey AU - Bukoski, Richard D AU - Kunos, George AD - Laboratory of Physiologic Studies, National Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, Bethesda, Md 20892-8115, USA. Y1 - 2004/10/05/ PY - 2004 DA - 2004 Oct 05 SP - 1996 EP - 2002 VL - 110 IS - 14 KW - Arachidonic Acids KW - 0 KW - Benzamides KW - Benzyl Compounds KW - Bornanes KW - Carbamates KW - Endocannabinoids KW - N-(4-hydroxyphenyl)arachidonylamide KW - OMDM-2 cpd KW - Piperidines KW - Polyunsaturated Alkamides KW - Pyrazoles KW - Receptor, Cannabinoid, CB1 KW - SR 144528 KW - cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester KW - Angiotensin II KW - 11128-99-7 KW - AM 251 KW - 3I4FA44MAI KW - Dronabinol KW - 7J8897W37S KW - Amidohydrolases KW - EC 3.5.- KW - fatty-acid amide hydrolase KW - EC 3.5.1.- KW - HU 211 KW - R6VT8U5372 KW - rimonabant KW - RML78EN3XE KW - anandamide KW - UR5G69TJKH KW - Abridged Index Medicus KW - Index Medicus KW - Ventricular Function, Left -- drug effects KW - Benzyl Compounds -- pharmacology KW - Carbamates -- pharmacology KW - Animals KW - Rats, Inbred WKY KW - Rats, Inbred SHR KW - Endothelium, Vascular -- metabolism KW - Vasodilation -- physiology KW - Rats, Inbred Dahl KW - Ventricular Function, Left -- physiology KW - Myocardium -- metabolism KW - Angiotensin II -- toxicity KW - Rats KW - Piperidines -- pharmacology KW - Models, Cardiovascular KW - Pyrazoles -- pharmacology KW - Rats, Sprague-Dawley KW - Benzamides -- pharmacology KW - Bornanes -- pharmacology KW - Vasodilation -- drug effects KW - Amidohydrolases -- antagonists & inhibitors KW - Up-Regulation KW - Male KW - Blood Pressure -- physiology KW - Hypertension -- physiopathology KW - Dronabinol -- pharmacology KW - Receptor, Cannabinoid, CB1 -- drug effects KW - Hypertension -- genetics KW - Vascular Resistance -- drug effects KW - Myocardial Contraction -- drug effects KW - Arachidonic Acids -- metabolism KW - Arachidonic Acids -- pharmacology KW - Dronabinol -- analogs & derivatives KW - Hypertension -- chemically induced KW - Receptor, Cannabinoid, CB1 -- physiology KW - Myocardial Contraction -- physiology KW - Blood Pressure -- drug effects KW - Vascular Resistance -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66934440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Endocannabinoids+acting+at+cannabinoid-1+receptors+regulate+cardiovascular+function+in+hypertension.&rft.au=B%C3%A1tkai%2C+S%C3%A1ndor%3BPacher%2C+P%C3%A1l%3BOsei-Hyiaman%2C+Douglas%3BRadaeva%2C+Svetlana%3BLiu%2C+Jie%3BHarvey-White%2C+Judith%3BOffert%C3%A1ler%2C+L%C3%A1szl%C3%B3%3BMackie%2C+Ken%3BRudd%2C+M+Audrey%3BBukoski%2C+Richard+D%3BKunos%2C+George&rft.aulast=B%C3%A1tkai&rft.aufirst=S%C3%A1ndor&rft.date=2004-10-05&rft.volume=110&rft.issue=14&rft.spage=1996&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=1524-4539&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-05-27 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-14 N1 - SuppNotes - Cited By: Hypertension. 2000 Feb;35(2):679-84 [10679517] Biochem J. 2000 Mar 15;346 Pt 3:835-40 [10698714] Eur J Pharmacol. 2001 Jul 6;423(2-3):203-10 [11448486] Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9371-6 [11470906] Hypertension. 2002 Feb;39(2):251-7 [11847193] Br J Pharmacol. 2002 Mar;135(5):1191-8 [11877326] Hypertension. 2002 Feb;39(2 Pt 2):690-4 [11882632] Am J Physiol Heart Circ Physiol. 2002 Jun;282(6):H2046-54 [12003810] J Biol Chem. 2002 Jun 7;277(23):20927-33 [11919181] J Am Coll Cardiol. 2002 Sep 4;40(5):1006-16 [12225730] J Neurosci. 2002 Nov 1;22(21):9612-7 [12417686] Chem Phys Lipids. 2002 Dec 31;121(1-2):83-9 [12505693] Nat Med. 2003 Jan;9(1):76-81 [12461523] Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1393-8 [12538878] Hypertension. 2003 Feb;41(2):249-54 [12574090] Circulation. 2003 Feb 18;107(6):896-904 [12591762] Mol Pharmacol. 2003 Mar;63(3):699-705 [12606780] Hypertension. 2003 Mar;41(3 Pt 2):757-62 [12623992] J Cardiovasc Pharmacol. 2003 Apr;41(4):657-64 [12658069] Br J Pharmacol. 2003 Apr;138(7):1320-32 [12711633] Eur J Pharmacol. 2004 Jan 26;484(2-3):249-57 [14744610] J Physiol. 2004 Jul 15;558(Pt 2):647-57 [15121805] Am J Med. 1973 Sep;55(3):281-94 [4746556] J Pharm Pharmacol. 1974 Mar;26(3):186-92 [4151077] Clin Pharmacol Ther. 1975 Sep;18(3):287-97 [1164818] Arch Int Pharmacodyn Ther. 1978 May;233(1):76-81 [686909] Circ Res. 1983 Aug;53(2):150-7 [6309428] Nature. 1990 Aug 9;346(6284):561-4 [2165569] Biochem J. 1992 Nov 15;288 ( Pt 1):79-85 [1445283] Nature. 1993 Sep 2;365(6441):61-5 [7689702] Eur J Pharmacol. 1995 May 24;278(3):279-83 [7589169] Br J Pharmacol. 1996 Aug;118(8):2023-8 [8864538] Hypertension. 1997 May;29(5):1204-10 [9149688] J Pharmacol Exp Ther. 1997 Jun;281(3):1030-7 [9190833] J Clin Invest. 1997 Sep 15;100(6):1538-46 [9294122] Eur J Pharmacol. 1997 Oct 15;337(1):R1-2 [9389389] Science. 1999 Jan 15;283(5400):401-4 [9888857] Am J Physiol. 1999 Jun;276(6 Pt 2):H2085-93 [10362691] Nature. 1999 Jul 29;400(6743):452-7 [10440374] Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14136-41 [10570211] N1 - Last updated - 2017-01-19 ER - TY - JOUR T1 - Effect of the Met344His mutation on the conformational dynamics of bovine beta-1,4-galactosyltransferase: crystal structure of the Met344His mutant in complex with chitobiose. AN - 66913406; 15449940 AB - Beta-1,4-galactosyltransferase (beta4Gal-T1) in the presence of manganese ion transfers galactose from UDP-galactose (UDP-Gal) to N-acetylglucosamine (GlcNAc) that is either free or linked to an oligosaccharide. Crystallographic studies on bovine beta4Gal-T1 have shown that the primary metal binding site is located in the hinge region of a long flexible loop, which upon Mn(2+) and UDP-Gal binding changes from an open to a closed conformation. This conformational change creates an oligosaccharide binding site in the enzyme. Neither UDP nor UDP analogues efficiently induce these conformational changes in the wild-type enzyme, thereby restricting the structural analysis of the acceptor binding site. The binding of Mn(2+) involves an uncommon coordination to the Sdelta atom of Met344; when it is mutated to His, the mutant M344H, in the presence of Mn(2+) and UDP-hexanolamine, readily changes to a closed conformation, facilitating the structural analysis of the enzyme bound with an oligosaccharide acceptor. Although the mutant M344H loses 98% of its Mn(2+)-dependent activity, it exhibits 25% of its activity in the presence of Mg(2+). The crystal structures of M344H-Gal-T1 in complex with either UDP-Gal.Mn(2+) or UDP-Gal.Mg(2+), determined at 2.3 A resolution, show that the mutant enzyme in these complexes is in a closed conformation, and the coordination stereochemistry of Mg(2+) is quite similar to that of Mn(2+). Although either Mn(2+) or Mg(2+), together with UDP-Gal, binds and changes the conformation of the M344H mutant to the closed one, it is the Mg(2+) complex that engages efficiently in catalyses. Thus, this property enabled us to crystallize the M344H mutant for the first time with the acceptor substrate chitobiose in the presence of UDP-hexanolamine and Mn(2+). The crystal structure determined at 2.3 A resolution reveals that the GlcNAc residue at the nonreducing end of chitobiose makes extensive hydrophobic interactions with the highly conserved Tyr286 residue. JF - Biochemistry AU - Ramakrishnan, Boopathy AU - Boeggeman, Elizabeth AU - Qasba, Pradman K AD - Structural Glycobiology Section, Laboratory of Experimental and Computational Biology, SAIC-Frederick, Inc., Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702-1201, USA. Y1 - 2004/10/05/ PY - 2004 DA - 2004 Oct 05 SP - 12513 EP - 12522 VL - 43 IS - 39 SN - 0006-2960, 0006-2960 KW - Disaccharides KW - 0 KW - Hexanes KW - Monosaccharides KW - Uridine Diphosphate Galactose KW - 2956-16-3 KW - Tyrosine KW - 42HK56048U KW - Manganese KW - 42Z2K6ZL8P KW - Histidine KW - 4QD397987E KW - chitobiose KW - 577-76-4 KW - Methionine KW - AE28F7PNPL KW - N-Acetyllactosamine Synthase KW - EC 2.4.1.90 KW - Magnesium KW - I38ZP9992A KW - Acetylglucosamine KW - V956696549 KW - Index Medicus KW - Crystallization KW - Animals KW - Acetylglucosamine -- metabolism KW - Hexanes -- chemistry KW - Structure-Activity Relationship KW - Cattle KW - Uridine Diphosphate Galactose -- chemistry KW - Manganese -- chemistry KW - Monosaccharides -- chemistry KW - Crystallography, X-Ray KW - Tyrosine -- metabolism KW - Magnesium -- chemistry KW - Carbohydrate Conformation KW - Catalysis KW - Protein Conformation KW - Mutagenesis, Site-Directed KW - Methionine -- genetics KW - N-Acetyllactosamine Synthase -- genetics KW - N-Acetyllactosamine Synthase -- chemistry KW - Thermodynamics KW - Histidine -- genetics KW - Disaccharides -- chemistry KW - N-Acetyllactosamine Synthase -- metabolism KW - Disaccharides -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66913406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+the+Met344His+mutation+on+the+conformational+dynamics+of+bovine+beta-1%2C4-galactosyltransferase%3A+crystal+structure+of+the+Met344His+mutant+in+complex+with+chitobiose.&rft.au=Ramakrishnan%2C+Boopathy%3BBoeggeman%2C+Elizabeth%3BQasba%2C+Pradman+K&rft.aulast=Ramakrishnan&rft.aufirst=Boopathy&rft.date=2004-10-05&rft.volume=43&rft.issue=39&rft.spage=12513&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-15 N1 - Date created - 2004-09-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1TW5; PDB; 1TVY; 1TW1 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Usefulness of Exercise Testing in the Prediction of Coronary Disease Risk Among Asymptomatic Persons as a Function of the Framingham Risk Score AN - 17849410; 6040011 AB - BACKGROUND: The purpose of this study is to determine the usefulness of exercise treadmill testing (ETT) among asymptomatic persons in predicting coronary heart disease (CHD) events over and above the Framingham CHD risk score. METHOD:S: and Results- Subjects included 3043 members of the Framingham Heart Study offspring cohort without CHD (1431 men and 1612 women; age, 45+/-9 years) who underwent ETT and were followed up for 18.2 years. The risk of developing CHD was evaluated relative to 3 exercise test variables: (1) ST- segment depression =>1 mm, (2) failure to achieve target heart rate (THR) of 85% predicted maximum, and (3) exercise capacity. In multivariable analyses that adjusted for age and Framingham CHD risk score, among men, ST-segment depression (hazard ratio [HR], 1.88; 95% CI, 1.21 to 2.91) and failure to achieve THR (HR, 1.70; 95% CI, 1.18 to 2.45) predicted higher CHD risk, whereas a greater exercise capacity predicted lower CHD risk (HR per MET, 0.94; 95% CI, 0.89 to 0.99). Although similar HRs were seen in women, those results were not statistically significant. Among men with 10-year predicted risk =>20%, failure to reach THR and ST-segment depression both more than doubled the risk of an event (HR, 2.66 and HR, 2.11, respectively), and each MET increment in exercise capacity reduced risk by 13% (HR, 0.87). CONCLUSIONS: Among asymptomatic men, ST-segment depression, failure to reach THR, and exercise capacity during ETT provided additional prognostic information in age- and Framingham risk score- adjusted models, particularly among those in the highest risk group (10-year predicted CHD risk of =>20%). The evaluation of exercise test variables in women is limited, given our sample size and the few CHD events in women. JF - Circulation AU - Balady, Gary J AU - Larson, Martin G AU - Vasan, Ramachandran S AU - Leip, Eric P AU - O'donnell, Christopher J AU - Levy, Daniel AD - NHLBI's Framingham Heart Study, Framingham, Mass (M.G.L., R.S.V., E.P.L., C.J.O., D.L.) Y1 - 2004/10/05/ PY - 2004 DA - 2004 Oct 05 SP - 1920 EP - 1925 PB - Lippincott Williams & Wilkins, Inc, 530 Walnut Street Philadelphia PA 19106-3621 USA, [URL:http://www.lww.com/] VL - 110 IS - 14 SN - 0009-7322, 0009-7322 KW - Physical Education Index KW - Evaluation KW - Age KW - Analysis KW - Risk factors KW - Heart rate KW - Failure KW - Exercise KW - Treadmill ergometry KW - Heart diseases KW - Circulatory system KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17849410?accountid=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=Circulation&rft.atitle=Usefulness+of+Exercise+Testing+in+the+Prediction+of+Coronary+Disease+Risk+Among+Asymptomatic+Persons+as+a+Function+of+the+Framingham+Risk+Score&rft.au=Balady%2C+Gary+J%3BLarson%2C+Martin+G%3BVasan%2C+Ramachandran+S%3BLeip%2C+Eric+P%3BO%27donnell%2C+Christopher+J%3BLevy%2C+Daniel&rft.aulast=Balady&rft.aufirst=Gary&rft.date=2004-10-05&rft.volume=110&rft.issue=14&rft.spage=1920&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=00097322&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Exercise; Risk factors; Age; Failure; Heart rate; Evaluation; Analysis; Circulatory system; Heart diseases; Treadmill ergometry ER - TY - JOUR T1 - The mutagenic effects of 7,12-dimethylbenz[a]anthacene, 3-methylcholanthrene and benzo[a]pyrene to the developing Syrian hamster fetus measured by an in vivo/in vitro mutation assay. AN - 66922669; 15450409 AB - The transplacental mutagenicity of three polycylic aromatic hydrocarbons, 7,12-dimethylbenz[a]anthacene (DMBA), 3-methylcholanthrene (MC) and benzo[a]pyrene (BP), was measured by an in vivo/in vitro mutation assay. Fetal sensitivity and dose-response characteristics with regard to transplacental mutagenesis by these compounds have never been quantified. In the current experiment, pregnant Syrian hamsters were exposed to these compounds at day 12 of gestation. Twenty-four hours later the fetuses were removed and their cells were allowed a 5-day expression time in culture. They were then seeded for colony formation and also for mutation selection by diphtheria toxin. DMBA at 0.2 mmol/kg (51.3 mg/kg) had an induced mutant frequency of 1.56 x 10(-4) mutants per surviving cell. This was 598 times the historical control. DMBA at 0.2 mmol/kg was 3.6 times more potent than the highly mutagenic positive control, ethylnitrosourea, at 1 mmol/kg. DMBA also caused a dose-dependent increase in cloning efficiency, which was highly correlated with mutation rate. BP and MC were less effective than DMBA, causing increased mutations that were 31.6 and 17.7 times the historical control, respectively, and for neither was there any correlation of mutation rate with cloning efficiency. The special effectiveness of DMBA as a transplacental mutagen may relate to its ability to cause increased cell division and fixation of DNA lesions as mutations. JF - Mutation research AU - Donovan, Paul J AU - Smith, George T AU - Nardone, Roland AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Building 538, Room 205E, MD 21702-1201, USA. donovapa@mail.ncifcrf.gov Y1 - 2004/10/04/ PY - 2004 DA - 2004 Oct 04 SP - 111 EP - 120 VL - 554 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Mutagens KW - 0 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Methylcholanthrene KW - 56-49-5 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Animals KW - Mesocricetus KW - Cricetinae KW - Fetus -- drug effects KW - Methylcholanthrene -- toxicity KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Benzo(a)pyrene -- toxicity KW - Mutagens -- toxicity KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66922669?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=The+mutagenic+effects+of+7%2C12-dimethylbenz%5Ba%5Danthacene%2C+3-methylcholanthrene+and+benzo%5Ba%5Dpyrene+to+the+developing+Syrian+hamster+fetus+measured+by+an+in+vivo%2Fin+vitro+mutation+assay.&rft.au=Donovan%2C+Paul+J%3BSmith%2C+George+T%3BNardone%2C+Roland&rft.aulast=Donovan&rft.aufirst=Paul&rft.date=2004-10-04&rft.volume=554&rft.issue=1-2&rft.spage=111&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 - 2004-11-02 N1 - Date created - 2004-09-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific and General Language Performance across Early Childhood: Stability and Gender Considerations AN - 85592209; 200413449 AB - Altogether 329 children participated in four longitudinal studies of specific & general language performance cumulatively from 1:1 to 6:10. Data were drawn from age-appropriate maternal questionnaires, maternal interviews, teacher reports, experimenter assessments & transcripts of children's own spontaneous speech. Language performance at each age & stability of individual differences across age in girls & boys were assessed separately & together. Across age, including the important transition from preschool to school, across multiple tests at each age & across multiple reporters, children showed moderate to strong stability of individual differences; girls & boys alike were stable. In the second through fifth years, but not before or after, girls consistently outperformed boys in multiple specific & general measures of language. 11 Tables, 97 References. [Reprinted by permission of Sage Publications, Ltd., copyright 2004.] JF - First Language AU - Bornstein, Marc H AU - Hahn, Chun-Shin AU - Haynes, O Maurice AD - National Instit Child Health & Human Development, Bethesda, MD Marc_H_Bornstein@nih.gov Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 267 EP - 304 VL - 24 IS - 3 SN - 0142-7237, 0142-7237 KW - Language Tests (44250) KW - Language Acquisition (41600) KW - Surveys (86000) KW - Sex Differences (77850) KW - Interviews (37950) KW - Spontaneous Speech (83500) KW - Longitudinal Studies (49900) KW - Communicative Competence (13650) KW - Children (11850) KW - article KW - 4015: psycholinguistics; child language acquisition UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85592209?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=First+Language&rft.atitle=Specific+and+General+Language+Performance+across+Early+Childhood%3A+Stability+and+Gender+Considerations&rft.au=Bornstein%2C+Marc+H%3BHahn%2C+Chun-Shin%3BHaynes%2C+O+Maurice&rft.aulast=Bornstein&rft.aufirst=Marc&rft.date=2004-10-01&rft.volume=24&rft.issue=3&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=First+Language&rft.issn=01427237&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2004-12-01 N1 - Last updated - 2016-09-27 N1 - CODEN - FILAE2 N1 - SubjectsTermNotLitGenreText - Language Tests (44250); Children (11850); Interviews (37950); Surveys (86000); Sex Differences (77850); Communicative Competence (13650); Language Acquisition (41600); Longitudinal Studies (49900); Spontaneous Speech (83500) ER - TY - JOUR T1 - Effect of monoamine reuptake inhibitor NS 2330 in advanced Parkinson's disease. AN - 85393619; pmid-15390018 AB - Dopamine reuptake blockers, by enhancing and stabilizing intrasynaptic transmitter levels, could help palliate motor dysfunction in Parkinson's disease. This randomized, double-blind, placebo-controlled study compared the acute effects of the monoamine uptake inhibitor NS 2330 to those of placebo in 9 relatively advanced parkinsonian patients. At the dose administered, no change in parkinsonian scores was found when NS 2330 was given alone or with levodopa. Moreover, NS 2330 coadministration did not appear to alter dyskinesia severity or the duration of the antiparkinsonian response to levodopa. The drug was well tolerated. Under the conditions of this study, the present results failed to support the usefulness of dopamine reuptake inhibition in the treatment of advanced Parkinson's disease.(c) 2004 Movement Disorder Society. JF - Movement disorders : official journal of the Movement Disorder Society AU - Bara-Jimenez, William AU - Dimitrova, Tzvetelina AU - Sherzai, Abdulah AU - Favit, Antonella AU - Mouradian, M M AU - Chase, Thomas N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 2004/10// PY - 2004 DA - Oct 2004 SP - 1183 EP - 1186 VL - 19 IS - 10 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Aged KW - *Antiparkinson Agents: therapeutic use KW - Benzothiazoles KW - Carbidopa: therapeutic use KW - Dopamine Plasma Membrane Transport Proteins KW - *Dopamine Uptake Inhibitors: therapeutic use KW - Double-Blind Method KW - Drug Combinations KW - Drug Therapy, Combination KW - Female KW - Humans KW - Indoles: therapeutic use KW - Levodopa: therapeutic use KW - Male KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Middle Aged KW - Nerve Tissue Proteins KW - Parkinson Disease: diagnosis KW - *Parkinson Disease: drug therapy KW - Pilot Projects KW - Thiazoles: therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85393619?accountid=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+monoamine+reuptake+inhibitor+NS+2330+in+advanced+Parkinson%27s+disease.&rft.au=Bara-Jimenez%2C+William%3BDimitrova%2C+Tzvetelina%3BSherzai%2C+Abdulah%3BFavit%2C+Antonella%3BMouradian%2C+M+M%3BChase%2C+Thomas+N&rft.aulast=Bara-Jimenez&rft.aufirst=William&rft.date=2004-10-01&rft.volume=19&rft.issue=10&rft.spage=1183&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 - Task-specific dystonia in tabla players. AN - 85387358; pmid-15389991 AB - Task-specific dystonia significantly impairs the performance of approximately 8% of musicians [Lederman RJ. Muscle Nerve 2003;27:549-561]. We describe hand dystonia in two professional musicians experienced while playing tabla, a percussion instrument.(c) 2004 Movement Disorder Society. JF - Movement disorders : official journal of the Movement Disorder Society AU - Ragothaman, Mona AU - Sarangmath, Nagaraja AU - Jayaram, Sachi AU - Swaminath, Pazhayannur V AU - Muthane, Uday AD - Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 2004/10// PY - 2004 DA - Oct 2004 SP - 1254 EP - 1256 VL - 19 IS - 10 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Adult KW - Botulinum Toxins, Type A: therapeutic use KW - Dystonia: drug therapy KW - *Dystonia: physiopathology KW - Humans KW - Injections, Intramuscular KW - Male KW - Middle Aged KW - Muscle Cramp: drug therapy KW - Muscle Cramp: physiopathology KW - *Music KW - Neuromuscular Agents: therapeutic use KW - *Wrist: physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85387358?accountid=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=Task-specific+dystonia+in+tabla+players.&rft.au=Ragothaman%2C+Mona%3BSarangmath%2C+Nagaraja%3BJayaram%2C+Sachi%3BSwaminath%2C+Pazhayannur+V%3BMuthane%2C+Uday&rft.aulast=Ragothaman&rft.aufirst=Mona&rft.date=2004-10-01&rft.volume=19&rft.issue=10&rft.spage=1254&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 - Founders of child neurology in Japan--Masaki Suzuki. AN - 85376144; pmid-15351074 JF - Brain & development AU - Kaga, Makiko AU - Nihei, Kenji AD - Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3, Kohnodai, Ichikawa, Chiba 272-0827, Japan. Y1 - 2004/10// PY - 2004 DA - Oct 2004 SP - 423 EP - 424 VL - 26 IS - 7 SN - 0387-7604, 0387-7604 KW - Index Medicus KW - National Library of Medicine KW - History, 20th Century KW - Humans KW - Japan KW - *Neurology: history KW - Neuropsychology: history KW - *Pediatrics: history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85376144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+%26+development&rft.atitle=Founders+of+child+neurology+in+Japan--Masaki+Suzuki.&rft.au=Kaga%2C+Makiko%3BNihei%2C+Kenji&rft.aulast=Kaga&rft.aufirst=Makiko&rft.date=2004-10-01&rft.volume=26&rft.issue=7&rft.spage=423&rft.isbn=&rft.btitle=&rft.title=Brain+%26+development&rft.issn=03877604&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2011-12-15 N1 - Last updated - 2012-07-13 ER - TY - JOUR T1 - Cadmium and cancer of prostate and testis AN - 787173266; 13661059 AB - Cancer of the prostate is an important and potentially fatal disease in humans but the etiology is yet undefined. Cadmium and cadmium compounds are known to be human carcinogens based on findings of increased risk to lung cancer among exposed workers, but a relationship between cancer of the prostate and/or testis in humans is unclear in spite of suggestive results in rats. Parenteral administration or oral exposure to cadmium can result in proliferate lesions and tumors of the prostate in rats. The ability of cadmium to produce neoplasms in the prostate of rats is atypically dose-related and only occurs in rats at doses below the threshold for significant testicular toxicity. Testicular androgen production is essential for the maintenance of the prostate and prostate tumors. The rat testis may also develop tumors if cadmium is given parenterally at high doses. Subsequent to testicular hemorrhagic necrosis, there will be loss of testosterone production and hyperplasia and neoplasia of testicular interstitial cells, thought to be a response to trophic hormone release from the pituitary. The pathogenesis of prostatic cadmium carcinogenesis might include aberrant gene expression resulting in stimulation of cell proliferation or blockage of apoptosis. Activation of transcription factors such as the metallothionein gene and activation of some proto-oncogenes may enhance cell proliferation with damaged DNA. Suppression of DNA repair would add to the population of cells with damaged DNA. Chemically induced apoptosis can be blocked by cadmium, facilitating aberrant cell accumulation. JF - BioMetals AU - Goyer, Robert A AU - Liu, Jie AU - Waalkes, Michael P AD - NCI at NIEHS, Research Triangle Park, NC, 27709, U.S.A Y1 - 2004/10// PY - 2004 DA - Oct 2004 SP - 555 EP - 558 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 17 IS - 5 SN - 0966-0844, 0966-0844 KW - Toxicology Abstracts KW - Testes KW - Apoptosis KW - Metallothionein KW - Carcinogens KW - Hemorrhage KW - Neoplasia KW - Gene expression KW - Necrosis KW - Interstitial cells KW - Pituitary KW - Hormone release KW - Cadmium KW - Proto-oncogenes KW - Lung cancer KW - Etiology KW - Tumors KW - Toxicity KW - DNA repair KW - Testosterone KW - Hyperplasia KW - Prostate cancer KW - Transcription factors KW - Carcinogenesis KW - Cell proliferation KW - Prostate KW - Transcription activation KW - Androgens KW - X 24360:Metals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/787173266?accountid=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=BioMetals&rft.atitle=Cadmium+and+cancer+of+prostate+and+testis&rft.au=Goyer%2C+Robert+A%3BLiu%2C+Jie%3BWaalkes%2C+Michael+P&rft.aulast=Goyer&rft.aufirst=Robert&rft.date=2004-10-01&rft.volume=17&rft.issue=5&rft.spage=555&rft.isbn=&rft.btitle=&rft.title=BioMetals&rft.issn=09660844&rft_id=info:doi/10.1023%2FB%3ABIOM.0000045738.59708.20 LA - Dutch DB - ProQuest Environmental Science Collection N1 - Date revised - 2012-03-01 N1 - Last updated - 2015-04-09 N1 - SubjectsTermNotLitGenreText - Testes; Apoptosis; Metallothionein; Carcinogens; Hemorrhage; Neoplasia; Gene expression; Necrosis; Pituitary; Interstitial cells; Hormone release; Cadmium; Proto-oncogenes; Lung cancer; Etiology; Toxicity; Tumors; DNA repair; Hyperplasia; Testosterone; Prostate cancer; Transcription factors; Carcinogenesis; Cell proliferation; Prostate; Transcription activation; Androgens DO - http://dx.doi.org/10.1023/B:BIOM.0000045738.59708.20 ER - TY - JOUR T1 - A large vision with a small focus: from the organ to the cell. AN - 67300261; 17411690 JF - Journal of the American College of Radiology : JACR AU - Wallner, Paul E AD - NCI/DCTD/RRP/CROB, EPN/6002, Rockville, MD 20892-7440, USA. wallnerp@mail.nih.gov Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 719 VL - 1 IS - 10 KW - Index Medicus KW - Sensitivity and Specificity KW - Radiology -- trends KW - Humans KW - Forecasting KW - Radiography KW - Research Design KW - Radiology -- methods KW - Radiation Genetics KW - Molecular Biology KW - Diagnostic Imaging -- trends KW - Cells -- diagnostic imaging KW - Diagnostic Imaging -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67300261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+College+of+Radiology+%3A+JACR&rft.atitle=A+large+vision+with+a+small+focus%3A+from+the+organ+to+the+cell.&rft.au=Wallner%2C+Paul+E&rft.aulast=Wallner&rft.aufirst=Paul&rft.date=2004-10-01&rft.volume=1&rft.issue=10&rft.spage=719&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+College+of+Radiology+%3A+JACR&rft.issn=1558-349X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2007-08-23 N1 - Date created - 2007-04-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Impulsivity in abstinent alcohol-dependent patients: relation to control subjects and type 1-/type 2-like traits. AN - 67284382; 15902907 AB - Extensive literature has linked behavior control problems in childhood to risk for alcoholism, but impulsivity in alcohol-dependent adults has not been well characterized. Using a variety of laboratory measures of impulsivity, we assessed whether detoxified alcohol-dependent patients [(ADP); n = 130] were more impulsive than control subjects [(CS); n = 41]. In comparison with CS, ADP demonstrated (1) increased rates of commission errors, but not omission errors, in a continuous performance test, (2) a more severe devaluation of delayed reward, (3) increased rates of risky responses in a new risk-taking paradigm, and (4) higher psychometric scores of impulsivity and aggression. Across all subjects, aggressiveness correlated significantly with severity of delay discounting. A post hoc analysis of data obtained for male ADP indicated that, in comparison with patients with late onset of problem drinking and no problem-drinking parent, those ADP with earlier age of problem drinking and who reported a problem-drinking father (type 2-like alcohol dependence) demonstrated faster response latencies and more responses to non-target stimuli (commission errors) in the continuous performance test, as well as higher psychometric aggression. In contrast, these subtypes of male ADP did not differ in delay discounting and risk taking. These findings collectively indicate that, in comparison with CS, ADP are more impulsive in several dimensions, with elevated impulsivity in a working memory task as well as aggressivity characteristic of alcohol-dependent men with type 2-like features. JF - Alcohol (Fayetteville, N.Y.) AU - Bjork, James M AU - Hommer, Daniel W AU - Grant, Steven J AU - Danube, Cinnamon AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Drive, Room 3C-103, Bethesda, MD 20892, USA. jbjork@mail.nih.gov PY - 2004 SP - 133 EP - 150 VL - 34 IS - 2-3 SN - 0741-8329, 0741-8329 KW - Index Medicus KW - Risk-Taking KW - Humans KW - Adult KW - Middle Aged KW - Neuropsychological Tests KW - Adolescent KW - Reaction Time -- physiology KW - Male KW - Female KW - Psychomotor Performance -- physiology KW - Impulsive Behavior -- psychology KW - Temperance -- psychology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67284382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+%28Fayetteville%2C+N.Y.%29&rft.atitle=Impulsivity+in+abstinent+alcohol-dependent+patients%3A+relation+to+control+subjects+and+type+1-%2Ftype+2-like+traits.&rft.au=Bjork%2C+James+M%3BHommer%2C+Daniel+W%3BGrant%2C+Steven+J%3BDanube%2C+Cinnamon&rft.aulast=Bjork&rft.aufirst=James&rft.date=2004-10-01&rft.volume=34&rft.issue=2-3&rft.spage=133&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 - 2005-07-11 N1 - Date created - 2005-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemotherapy dose density in early-stage breast cancer and non-Hodgkin's lymphoma. AN - 67213917; 15628832 AB - Delivering standard-dose chemotherapy on schedule is important for survival in early-stage breast cancer and non-Hodgkin's lymphoma. Trials of dose-escalated regimens, in which higher-than-standard doses of chemotherapy are used, have produced equivocal results. In contrast, dose-dense regimens, in which standard doses are given with shorter (usually 14-day) intervals between cycles, have been more efficacious than standard 21-day regimens in trials in both early-stage breast cancer and non-Hodgkin's lymphoma. Furthermore, a shorter course of chemotherapy is likely to cause less disruption in patients' lives. Despite the evidence of the importance of maintaining chemotherapy dose intensity (the amount of drug administered/unit of time), undertreatment of patients with early-stage breast cancer and non-Hodgkin's lymphoma is common. Neutropenia is the primary dose-limiting toxicity of many chemotherapy regimens, and it is frequently managed by dose reductions and delays that decrease dose intensity. Colony-stimulating factors reduce the prevalence and severity of neutropenia and its complications, and their proactive use can improve adherence to the planned schedule of both standard-dose and dose-dense chemotherapy The promising results with dose-dense chemotherapy in early-stage breast cancer and non-Hodgkin's lymphoma indicate that it should be tested in patients with other chemosensitive tumors. JF - Pharmacotherapy AU - Goldspiel, Barry R AD - Department of Pharmacy, National Institutes of Health Clinical Center, Bethesda, Maryland 20892-1196, USA. bgoldspiel@nih.gov Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 1347 EP - 1357 VL - 24 IS - 10 SN - 0277-0008, 0277-0008 KW - Antineoplastic Agents KW - 0 KW - Index Medicus KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Humans KW - Drug-Related Side Effects and Adverse Reactions KW - Breast Neoplasms -- drug therapy KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Antineoplastic Agents -- therapeutic use KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67213917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Chemotherapy+dose+density+in+early-stage+breast+cancer+and+non-Hodgkin%27s+lymphoma.&rft.au=Goldspiel%2C+Barry+R&rft.aulast=Goldspiel&rft.aufirst=Barry&rft.date=2004-10-01&rft.volume=24&rft.issue=10&rft.spage=1347&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-04 N1 - Date created - 2005-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of alcoholic fatty liver and fibrosis in rhesus monkeys fed a low n-3 fatty acid diet. AN - 67178187; 15597091 AB - The amount and type of dietary fat seem to be important factors that modulate the development of alcohol-induced liver steatosis and fibrosis. Various alcohol-feeding studies in animals have been used to model some of the symptoms that occur in liver disease in humans. Rhesus monkeys (Macaca mulatta) were maintained on a diet that had a very low concentration of alpha-linolenic acid and were given free access to an artificially sweetened 7% ethanol solution. Control and ethanol-consuming animals were maintained on a diet in which the linoleate content was adequate (1.4% of energy); however, alpha-linoleate represented only 0.08% of energy. Liver specimens were obtained, and the fatty acid composition of the liver phospholipids, cholesterol esters, and triglycerides of the two groups were compared at 5 years and histopathology of tissue samples were compared at 3 and 5 years. The mean consumption of ethanol for this group over a 5-year period was 2.4 g.kg.day. As a consequence of the ethanol-dietary treatment, there were significantly lower concentrations of several polyunsaturated fatty acids in the liver phospholipids of the alcohol-treated group, including arachidonic acid and most of the n-3 fatty acids and particularly docosahexaenoic acid, when compared with dietary controls. Liver specimens from animals in the ethanol group at 5 years showed a marked degree of steatosis, both focal and diffuse cellular necrosis, and an increase in the development of fibrosis compared with specimens obtained at 3 years and with those from dietary controls, in which there was no evidence of fibrotic lesions. These findings suggest that the advancement of ethanol-induced liver disease in rhesus monkeys may be modulated by the amount and type of dietary essential fatty acids and that a marginal intake of n-3 fatty acids may be a permissive factor in the development of liver disease in primates. JF - Alcoholism, clinical and experimental research AU - Pawlosky, Robert J AU - Salem, Norman AD - Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Rockville, Maryland 20852, USA. bpawl@mail.nih.gov Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 1569 EP - 1576 VL - 28 IS - 10 SN - 0145-6008, 0145-6008 KW - Dietary Fats, Unsaturated KW - 0 KW - Fatty Acids, Omega-3 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Dietary Fats, Unsaturated -- pharmacology KW - Animals KW - Macaca mulatta KW - Dietary Fats, Unsaturated -- therapeutic use KW - Male KW - Liver Cirrhosis -- prevention & control KW - Liver -- pathology KW - Liver -- drug effects KW - Fatty Liver, Alcoholic -- prevention & control KW - Fatty Liver, Alcoholic -- metabolism KW - Fatty Liver, Alcoholic -- etiology KW - Fatty Acids, Omega-3 -- therapeutic use KW - Fatty Acids, Omega-3 -- pharmacology KW - Liver Cirrhosis -- metabolism KW - Liver -- metabolism KW - Ethanol -- toxicity KW - Liver Cirrhosis -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67178187?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Development+of+alcoholic+fatty+liver+and+fibrosis+in+rhesus+monkeys+fed+a+low+n-3+fatty+acid+diet.&rft.au=Pawlosky%2C+Robert+J%3BSalem%2C+Norman&rft.aulast=Pawlosky&rft.aufirst=Robert&rft.date=2004-10-01&rft.volume=28&rft.issue=10&rft.spage=1569&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 - 2005-01-18 N1 - Date created - 2004-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Substituted amphetamines that produce long-term serotonin depletion in rat brain ("neurotoxicity") do not decrease serotonin transporter protein expression. AN - 67065788; 15542713 AB - Administration of high-dose D-fenfluramine (D-FEN) or parachloroamphetamine (PCA) produces 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 few studies have measured SERT protein levels. Thus, 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 to 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 D-FEN- and PCA-induced decreases in tissue 5-HT and SERT binding sites reflect neuroadaptive changes rather than neurotoxic effects. JF - Annals of the New York Academy of Sciences AU - Rothman, Richard B AU - Jayanthi, Subramaniam AU - Cadet, Jean L AU - Wang, Xiaoying AU - Dersch, Christina M AU - Baumann, Michael H AD - Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. rrothman@intra.nida.nih.gov Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 151 EP - 161 VL - 1025 SN - 0077-8923, 0077-8923 KW - Amphetamines KW - 0 KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Serotonin Plasma Membrane Transport Proteins KW - Slc6a4 protein, rat KW - Serotonin KW - 333DO1RDJY KW - Index Medicus KW - Rats KW - Protein Binding -- physiology KW - Animals KW - Rats, Sprague-Dawley KW - Time KW - Gene Expression Regulation -- physiology KW - Protein Binding -- drug effects KW - Gene Expression Regulation -- drug effects KW - Male KW - Membrane Glycoproteins -- biosynthesis KW - Brain -- drug effects KW - Nerve Tissue Proteins -- biosynthesis KW - Membrane Transport Proteins -- biosynthesis KW - Brain -- metabolism KW - Serotonin -- metabolism KW - Nerve Tissue Proteins -- genetics KW - Membrane Transport Proteins -- genetics KW - Membrane Glycoproteins -- genetics KW - Amphetamines -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67065788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Substituted+amphetamines+that+produce+long-term+serotonin+depletion+in+rat+brain+%28%22neurotoxicity%22%29+do+not+decrease+serotonin+transporter+protein+expression.&rft.au=Rothman%2C+Richard+B%3BJayanthi%2C+Subramaniam%3BCadet%2C+Jean+L%3BWang%2C+Xiaoying%3BDersch%2C+Christina+M%3BBaumann%2C+Michael+H&rft.aulast=Rothman&rft.aufirst=Richard&rft.date=2004-10-01&rft.volume=1025&rft.issue=&rft.spage=151&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 - 2005-02-18 N1 - Date created - 2004-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular genetics of substance abuse vulnerability: remarkable recent convergence of genome scan results. AN - 67064123; 15542694 AB - Classical genetic studies document strong complex genetic contributions to abuse of multiple addictive substances. Goals of molecular genetic studies of addiction include: (1) locating chromosomal regions that contain allelic gene variants that contribute to vulnerability to drug dependence and (2) discovering which alleles of which gene markers and which genes provide these enhanced vulnerabilities. Genome scanning provides an approach to these goals. Until recently, data from genome scanning studies did not convincingly identify chromosomal positions for allelic variants predisposing to substance dependence. Nominal results of initial genome scans for alcohol and nicotine dependence failed to display much agreement; no two studies' results seemed to identify the same chromosomal regions for addiction vulnerability alleles. However, recent data from our association-based genome scans for illegal addictions, reanalyses of prior linkage-based results, and data from even newer linkage-based genome scans now provide a striking body of converging results. Sixteen chromosomal regions are identified by reproducible positive results obtained in multiple populations. These 16 regions are thus good candidates to harbor common allelic variants that confer human vulnerability to addiction to several classes of substances. Genomic markers that identify allelic variants that reproducibly alter addiction vulnerability in studies in several populations provide powerful tools for clinical research in addictions and addiction treatments. JF - Annals of the New York Academy of Sciences AU - Uhl, George R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse-International Research Program, National Institutes of Health, Baltimore, MD 21224, USA. guhl@intra.nida.nih.gov Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 1 EP - 13 VL - 1025 SN - 0077-8923, 0077-8923 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Genetic Markers -- genetics KW - Humans KW - Genetic Variation -- genetics KW - Gene Frequency -- genetics KW - Genome, Human KW - Genetic Linkage -- genetics KW - Genetic Predisposition to Disease KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67064123?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Molecular+genetics+of+substance+abuse+vulnerability%3A+remarkable+recent+convergence+of+genome+scan+results.&rft.au=Uhl%2C+George+R&rft.aulast=Uhl&rft.aufirst=George&rft.date=2004-10-01&rft.volume=1025&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 - 2005-02-18 N1 - Date created - 2004-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Progression of cisplatin-induced nephrotoxicity in a carnitine-depleted rat model. AN - 67045818; 15347908 AB - This study has been initiated to investigate whether endogenous carnitine depletion and/or carnitine deficiency is an additional risk factor and/or a mechanism in cisplatin-induced nephrotoxicity and to gain insights into the possibility of a mechanism-based protection by L-carnitine against this toxicity. 60 male Sprague-Dawley rats were divided into six groups of 10 animals each and received one of the following treatments: The first three groups were injected intraperitoneally with normal saline, L-carnitine (500 mg/kg), and D-carnitine (750 mg/kg), respectively, for 10 successive days. The 4th, 5th, and 6th groups were injected intraperitoneally with the same doses of normal saline, L-carnitine and D-carnitine, respectively, for 5 successive days before and after a single dose of cisplatin (7 mg/kg). Six days after cisplatin treatment, the animals were sacrificed, and serum as well as kidneys were isolated and analyzed. A single dose of cisplatin resulted in a significant increase in blood urea nitrogen (BUN), serum creatinine, malondialdehyde (MDA) and nitric oxide (NO) and a significant decrease in total carnitine, reduced glutathione (GSH) and adenosine triphosphate (ATP) content in kidney tissues. Interestingly, L-carnitine supplementation attenuated cisplatin-induced nephrotoxicity manifested by normalizing the increase of serum creatinine, BUN, MDA and NO and the decrease in total carnitine, GSH and ATP content in kidney tissues. In the carnitine-depleted rat model, cisplatin induced a progressive increase in serum creatinine and BUN as well as a progressive reduction in total carnitine and ATP content in kidney tissue. Histopathological examination of kidney tissues confirmed the biochemical data, i.e. L-carnitine supplementation protected against cisplatin-induced kidney damage, whereas D-carnitine aggravated cisplatin-induced renal injury. Data from this study suggest that: (1) oxidative stress plays an important role in cisplatin-induced kidney damage; (2) carnitine deficiency should be viewed as an additional risk factor and/or a mechanism in cisplatin-induced renal dysfunction, and (3) L-carnitine supplementation attenuates cisplatin-induced renal dysfunction. Copyright (c) 2004 S. Karger AG, Basel. JF - Chemotherapy AU - Sayed-Ahmed, Mohamed M AU - Eissa, Maha A AU - Kenawy, Sanaa A AU - Mostafa, Nadia AU - Calvani, Menotti AU - Osman, Abdel-Moneim M AD - Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Fum El-Khalig, Kasr El-Aini Street, Cairo, Egypt. mmsayedahmed@hotmail.com Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 162 EP - 170 VL - 50 IS - 4 SN - 0009-3157, 0009-3157 KW - Antineoplastic Agents KW - 0 KW - Cisplatin KW - Q20Q21Q62J KW - Carnitine KW - S7UI8SM58A KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Kidney -- pathology KW - Risk Factors KW - Oxidative Stress KW - Kidney -- drug effects KW - Disease Models, Animal KW - Male KW - Carnitine -- deficiency KW - Cisplatin -- toxicity KW - Carnitine -- metabolism KW - Antineoplastic Agents -- toxicity KW - Kidney Diseases -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67045818?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemotherapy&rft.atitle=Progression+of+cisplatin-induced+nephrotoxicity+in+a+carnitine-depleted+rat+model.&rft.au=Sayed-Ahmed%2C+Mohamed+M%3BEissa%2C+Maha+A%3BKenawy%2C+Sanaa+A%3BMostafa%2C+Nadia%3BCalvani%2C+Menotti%3BOsman%2C+Abdel-Moneim+M&rft.aulast=Sayed-Ahmed&rft.aufirst=Mohamed&rft.date=2004-10-01&rft.volume=50&rft.issue=4&rft.spage=162&rft.isbn=&rft.btitle=&rft.title=Chemotherapy&rft.issn=00093157&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-02-07 N1 - Date created - 2004-11-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel antimicrobial indolizinium alkaloid from Aniba panurensis. AN - 67000454; 15497951 AB - Activity-guided fractionation of an Aniba panurensis organic solvent extract has led to the isolation of the novel alkaloid 6,8-didec-(1Z)-enyl-5,7-dimethyl-2,3-dihydro-1H-indolizinium, as the trifluoroacetic acid salt (1). Its structure was determined by NMR and mass spectrometry. Bioassays performed in vitro demonstrated toxicity of compound 1 to a drug-resistant strain of Candida albicans. JF - Journal of natural products AU - Klausmeyer, Paul AU - Chmurny, Gwendolyn N AU - McCloud, Thomas G AU - Tucker, Kenneth D AU - Shoemaker, Robert H AD - Natural Products Support Group, Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc, National Cancer Institute-Frederick, Maryland 21702-1201, USA. Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 1732 EP - 1735 VL - 67 IS - 10 SN - 0163-3864, 0163-3864 KW - 6,8-didec-(1Z)-enyl-5,7-dimethyl-2,3-dihydro-1H-indolizinium, trifluoroacetic acid salt KW - 0 KW - Antifungal Agents KW - Indole Alkaloids KW - Index Medicus KW - Molecular Structure KW - Nuclear Magnetic Resonance, Biomolecular KW - Enterococcus faecium -- drug effects KW - Cryptococcus neoformans -- drug effects KW - Staphylococcus aureus -- drug effects KW - Microbial Sensitivity Tests KW - Guyana KW - Indole Alkaloids -- isolation & purification KW - Antifungal Agents -- pharmacology KW - Antifungal Agents -- chemistry KW - Antifungal Agents -- isolation & purification KW - Indole Alkaloids -- chemistry KW - Lauraceae -- chemistry KW - Indole Alkaloids -- pharmacology KW - Plants, Medicinal -- chemistry KW - Candida albicans -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/67000454?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=A+novel+antimicrobial+indolizinium+alkaloid+from+Aniba+panurensis.&rft.au=Klausmeyer%2C+Paul%3BChmurny%2C+Gwendolyn+N%3BMcCloud%2C+Thomas+G%3BTucker%2C+Kenneth+D%3BShoemaker%2C+Robert+H&rft.aulast=Klausmeyer&rft.aufirst=Paul&rft.date=2004-10-01&rft.volume=67&rft.issue=10&rft.spage=1732&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 - 2004-12-09 N1 - Date created - 2004-10-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of carboxypeptidase E and gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray. AN - 66985030; 15492986 AB - Pulmonary neuroendocrine tumors vary dramatically in their malignant behavior. Their classification, based on histological examination, is often difficult. In search of molecular and prognostic markers for these tumors, we used cDNA microarray analysis of human transcripts against reference RNA from a well-characterized immortalized bronchial epithelial cell line, BEAS-2B. Tumor cells were isolated by laser-capture microdissection from primary tumors of 17 typical carcinoids, small cell lung cancers, and large cell neuroendocrine carcinomas. An unsupervised, hierarchical clustering algorithm resulted in a precise classification of each tumor subtype according to the proposed histological classification. Selection of genes, using supervised analysis, resulted in the identification of 198 statistically significant genes (P <.004) that also accurately discriminated between 3 predefined tumor subtypes. Two-by-two comparisons of these genes identified classifier genes that distinguished each tumor subtype from the others. Changes in expression of selected differentially expressed genes for each tumor subtype were internally validated by real-time reverse-transcription polymerase chain reaction. Expression of 2 potential classifier gene products, carboxypeptidase E (CPE) and gamma-glutamyl hydrolase (GGH), was validated by immunohistochemistry and cross-validated on additional archival samples of pulmonary neuroendocrine tumors. Kaplan-Meier survival analysis revealed that immunostaining for CPE was a statistically significant predictor of good prognosis, whereas GGH expression correlated with poor prognosis. Thus, cDNA microarray analysis led to the identification of 2 novel biomarkers that should facilitate molecular diagnosis and further study of pulmonary neuroendocrine tumors. JF - Human pathology AU - He, Ping AU - Varticovski, Lyuba AU - Bowman, Elise D AU - Fukuoka, Junya AU - Welsh, Judith A AU - Miura, Koh AU - Jen, Jin AU - Gabrielson, Edward AU - Brambilla, Elisabeth AU - Travis, William D AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 1196 EP - 1209 VL - 35 IS - 10 SN - 0046-8177, 0046-8177 KW - Biomarkers, Tumor KW - 0 KW - Carboxypeptidase H KW - EC 3.4.17.10 KW - gamma-Glutamyl Hydrolase KW - EC 3.4.19.9 KW - Index Medicus KW - Gene Expression Profiling KW - Survival Rate KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Prognosis KW - Immunohistochemistry KW - Lung Neoplasms -- diagnosis KW - gamma-Glutamyl Hydrolase -- genetics KW - Neuroendocrine Tumors -- genetics KW - Neuroendocrine Tumors -- diagnosis KW - Carboxypeptidase H -- genetics KW - Lung Neoplasms -- genetics KW - Lung Neoplasms -- mortality KW - Neuroendocrine Tumors -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66985030?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+pathology&rft.atitle=Identification+of+carboxypeptidase+E+and+gamma-glutamyl+hydrolase+as+biomarkers+for+pulmonary+neuroendocrine+tumors+by+cDNA+microarray.&rft.au=He%2C+Ping%3BVarticovski%2C+Lyuba%3BBowman%2C+Elise+D%3BFukuoka%2C+Junya%3BWelsh%2C+Judith+A%3BMiura%2C+Koh%3BJen%2C+Jin%3BGabrielson%2C+Edward%3BBrambilla%2C+Elisabeth%3BTravis%2C+William+D%3BHarris%2C+Curtis+C&rft.aulast=He&rft.aufirst=Ping&rft.date=2004-10-01&rft.volume=35&rft.issue=10&rft.spage=1196&rft.isbn=&rft.btitle=&rft.title=Human+pathology&rft.issn=00468177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-10 N1 - Date created - 2004-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of angiogenesis by growth factor receptor bound protein 2-Src homology 2 domain bound antagonists. AN - 66976302; 15486196 AB - Growth factor receptor bound protein 2 (Grb2) is an intracellular adaptor protein that participates in the signal transduction cascades of several angiogenic factors, including hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor. We described previously the potent blockade of hepatocyte growth factor-stimulated cell motility, matrix invasion, and epithelial tubulogenesis by synthetic Grb2-Src homology 2 (SH2) domain binding antagonists. Here, we show that these binding antagonists block basic morphogenetic events required for angiogenesis, including hepatocyte growth factor-, vascular endothelial growth factor-, and basic fibroblast growth factor-stimulated endothelial cell proliferation and migration, as well as phorbol 12-myristate 13-acetate-stimulated endothelial cell migration and matrix invasion. The Grb2-SH2 domain binding antagonists also impair angiogenesis in vitro, as shown by the inhibition of cord formation by macrovascular endothelial cells on Matrigel. We further show that a representative compound inhibits angiogenesis in vivo as measured using a chick chorioallantoic membrane assay. These results suggest that Grb2 is an important mediator of key proangiogenic events, with potential application to pathologic conditions where neovascularization contributes to disease progression. In particular, the well-characterized role of Grb2 in signaling cell cycle progression together with our present findings suggests that Grb2-SH2 domain binding antagonists have the potential to act as anticancer drugs that target both tumor and vascular cell compartments. JF - Molecular cancer therapeutics AU - Soriano, Jesus V AU - Liu, Ningfei AU - Gao, Yang AU - Yao, Zhu-Jun AU - Ishibashi, Toshio AU - Underhill, Charles AU - Burke, Terrence R AU - Bottaro, Donald P AD - Cellular and Molecular Biology, National Cancer Institute, Building 10, Room 2B47, 9000 Rockville Pike, Bethesda, MD 20892-1501, USA. Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 1289 EP - 1299 VL - 3 IS - 10 SN - 1535-7163, 1535-7163 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Drug Combinations KW - GRB2 Adaptor Protein KW - GRB2 protein, human KW - Growth Substances KW - Laminin KW - Proteoglycans KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - matrigel KW - 119978-18-6 KW - Collagen KW - 9007-34-5 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Fibroblast Growth Factor 2 -- metabolism KW - Cell Movement KW - Animals KW - Endothelium, Vascular -- metabolism KW - Extracellular Matrix -- metabolism KW - Humans KW - Chick Embryo KW - Disease Progression KW - Cell Line, Tumor KW - Cell Proliferation KW - Protein Binding KW - src Homology Domains KW - Proteoglycans -- pharmacology KW - Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Models, Chemical KW - Collagen -- pharmacology KW - Laminin -- pharmacology KW - Signal Transduction KW - Cell Line KW - Adaptor Proteins, Signal Transducing -- metabolism KW - Adaptor Proteins, Signal Transducing -- physiology KW - Neovascularization, Pathologic KW - Growth Substances -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66976302?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Inhibition+of+angiogenesis+by+growth+factor+receptor+bound+protein+2-Src+homology+2+domain+bound+antagonists.&rft.au=Soriano%2C+Jesus+V%3BLiu%2C+Ningfei%3BGao%2C+Yang%3BYao%2C+Zhu-Jun%3BIshibashi%2C+Toshio%3BUnderhill%2C+Charles%3BBurke%2C+Terrence+R%3BBottaro%2C+Donald+P&rft.aulast=Soriano&rft.aufirst=Jesus&rft.date=2004-10-01&rft.volume=3&rft.issue=10&rft.spage=1289&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 - 2005-04-21 N1 - Date created - 2004-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonmyeloablative transplantation for solid tumors: a new frontier for allogeneic immunotherapy. AN - 66974158; 15485320 AB - The failure of conventional chemotherapy to improve survival in a large percentage of patients with advanced solid tumors has prompted the development of alternative anticancer approaches. Conventional allogeneic hematopoietic stem cell transplantation (HSCT) relies on myeloablative conditioning to eradicate the underlying disease, as well as suppress the patient's immune response, allowing engraftment of the donor's lymphohematopoietic system. Such preparative regimens are frequently associated with serious hematologic and nonhematologic toxicities, resulting in substantial morbidity and mortality. A significant curative component of allogeneic HSCT is the immune-mediated graft-versus-tumor (GVT) effect. Nonmyeloablative preparative regimens were designed to suppress host immunity to allow for sufficient engraftment of the donor immune system for the subsequent generation of GVT effects. These relatively low-dose preparative regimens are generally well tolerated and are associated with a reduction in the risk of transplant-related mortality. Nonmyeloablative HSCT provides a safer platform to explore the efficacy of allogeneic HSCT in patients with solid tumors. Initial reports have demonstrated that GVT may occur against several different solid tumors, including renal cell carcinoma, ovarian cancer, breast cancer and others. Based on these preliminary encouraging results, further exploration of nonmyeloablative HSCT for solid tumors is clearly warranted. The development of strategies to decrease graft-versus-host disease while enhancing post-transplant antitumor immunity will hopefully be forthcoming in the near future. JF - Expert review of anticancer therapy AU - Espinoza-Delgado, Igor AU - Childs, Richard W AD - National Institute on Aging, Section of Hematology-Oncology, 5600 Nathan Shock Drive, Room 4C10, Baltimore, MD 21224, USA. espinozaig@grc.nia.nih.gov Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 865 EP - 875 VL - 4 IS - 5 KW - Index Medicus KW - Graft vs Host Disease -- immunology KW - Humans KW - Transplantation, Homologous KW - Neoplasms -- therapy KW - Neoplasms -- immunology KW - Graft vs Tumor Effect -- immunology KW - Hematopoietic Stem Cell Transplantation KW - Immunotherapy -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66974158?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+review+of+anticancer+therapy&rft.atitle=Nonmyeloablative+transplantation+for+solid+tumors%3A+a+new+frontier+for+allogeneic+immunotherapy.&rft.au=Espinoza-Delgado%2C+Igor%3BChilds%2C+Richard+W&rft.aulast=Espinoza-Delgado&rft.aufirst=Igor&rft.date=2004-10-01&rft.volume=4&rft.issue=5&rft.spage=865&rft.isbn=&rft.btitle=&rft.title=Expert+review+of+anticancer+therapy&rft.issn=1744-8328&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2006-02-07 N1 - Date created - 2004-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Blockade of mesolimbic dopamine D3 receptors inhibits stress-induced reinstatement of cocaine-seeking in rats. AN - 66964991; 15083257 AB - The dopamine (DA) D3 receptor is preferentially expressed in the mesolimbic system. We have previously shown that selective D3 receptor blockade by the novel D3 antagonist SB-277011A inhibits cocaine's reinforcing action and cocaine-induced reinstatement of cocaine-seeking behavior. In the present study, we investigated whether SB-277011A similarly inhibits stress-induced reinstatement of cocaine-seeking behavior. Rats were allowed to self-administer cocaine (0.5 mg/kg per infusion, 3 h per session) for 10-14 days, followed by a once-daily extinction session for 7-14 days during which saline was substituted for cocaine. Extinction criteria were fewer than ten lever-presses per 3-h session for at least 3 consecutive days. After cocaine-seeking behavior was extinguished, each animal was tested twice for footshock-stress-induced reinstatement, once with vehicle (25% hydroxypropyl-beta-cyclodextrin) and once with one of three doses of SB-277011A in counterbalanced fashion. During the last 3 days of cocaine self-administration (SA), active lever-presses were approximately 100 per session under fixed-ratio 2 reinforcement (approximately 25 mg/kg cocaine per session). After extinction, intermittent footshock (10 min, 0.5 mA, 0.5 s on with a mean inter-shock interval of 40 s) robustly reinstated the cocaine-seeking behavior (8.4+/-3.6 active lever-presses in last extinction session to 35.3+/-5.2 in animals after footshock stress). Intraperitoneal (i.p.) injections of SB-277011A (3, 6, and 12 mg/kg) dose-dependently blocked stress-induced reinstatement of cocaine-seeking. Reinstatement was also blocked by microinjections of SB-277011A (1.5 microg/0.5 microl per side) bilaterally into the nucleus accumbens, but not into the dorsal striatum. The mesolimic DA D3 receptor plays an important role in mediating stress-induced reinstatement. JF - Psychopharmacology AU - Xi, Zheng-Xiong AU - Gilbert, Jeremy AU - Campos, Arlene C AU - Kline, Nicole AU - Ashby, Charles R AU - Hagan, Jim J AU - Heidbreder, Christian A AU - Gardner, Eliot L AD - Neuropsychopharmacology Section, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. zxi@intra.nida.nih.gov Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 57 EP - 65 VL - 176 IS - 1 SN - 0033-3158, 0033-3158 KW - Dopamine D2 Receptor Antagonists KW - 0 KW - Drd3 protein, rat KW - Nitriles KW - Receptors, Dopamine D2 KW - Receptors, Dopamine D3 KW - SB 277011 KW - Tetrahydroisoquinolines KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Tetrahydroisoquinolines -- therapeutic use KW - Conditioning, Operant -- drug effects KW - Animals KW - Substance Withdrawal Syndrome -- complications KW - Rats, Long-Evans KW - Conditioning, Operant -- physiology KW - Nucleus Accumbens -- ultrastructure KW - Rats KW - Self Administration -- methods KW - Corpus Striatum -- drug effects KW - Extinction, Psychological -- drug effects KW - Male KW - Nitriles -- pharmacology KW - Infusions, Intravenous KW - Nucleus Accumbens -- drug effects KW - Substance Withdrawal Syndrome -- prevention & control KW - Reinforcement (Psychology) KW - Tetrahydroisoquinolines -- pharmacology KW - Extinction, Psychological -- physiology KW - Microinjections KW - Nitriles -- therapeutic use KW - Cocaine -- administration & dosage KW - Nucleus Accumbens -- physiology KW - Cocaine -- pharmacokinetics KW - Stress, Psychological -- physiopathology KW - Cocaine-Related Disorders -- physiopathology KW - Receptors, Dopamine D2 -- drug effects KW - Receptors, Dopamine D2 -- physiology KW - Cocaine-Related Disorders -- complications KW - Secondary Prevention KW - Cocaine-Related Disorders -- prevention & control KW - Stress, Psychological -- prevention & control KW - Stress, Psychological -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66964991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Blockade+of+mesolimbic+dopamine+D3+receptors+inhibits+stress-induced+reinstatement+of+cocaine-seeking+in+rats.&rft.au=Xi%2C+Zheng-Xiong%3BGilbert%2C+Jeremy%3BCampos%2C+Arlene+C%3BKline%2C+Nicole%3BAshby%2C+Charles+R%3BHagan%2C+Jim+J%3BHeidbreder%2C+Christian+A%3BGardner%2C+Eliot+L&rft.aulast=Xi&rft.aufirst=Zheng-Xiong&rft.date=2004-10-01&rft.volume=176&rft.issue=1&rft.spage=57&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-03-29 N1 - Date created - 2004-10-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Behav Pharmacol. 2002 Sep;13(5-6):355-66 [12394411] Psychopharmacology (Berl). 2002 Oct;163(3-4):265-82 [12373428] Neuropsychopharmacology. 2003 Feb;28(2):329-38 [12589386] Synapse. 2003 Jun 1;48(3):154-6 [12645041] Neuropsychopharmacology. 2003 Jul;28(7):1272-80 [12700694] Psychopharmacology (Berl). 2003 Jul;168(1-2):3-20 [12402102] Psychopharmacology (Berl). 2003 Jul;168(1-2):21-30 [12695875] Psychopharmacology (Berl). 2003 Jul;168(1-2):31-41 [12721778] J Med Chem. 2003 Aug 28;46(18):3822-39 [12930145] Biochem Pharmacol. 1992 Feb 18;43(4):659-66 [1347215] Brain Res. 1991 Nov 15;564(2):203-19 [1839781] J Psychoactive Drugs. 1992 Apr-Jun;24(2):213-22 [1507002] J Neurochem. 1993 Feb;60(2):602-12 [7678287] Neuroscience. 1993 Apr;53(3):695-703 [7683777] Science. 1993 Jun 18;260(5115):1814-6 [8099761] Brain Res. 1993 Sep 3;621(1):65-70 [8221074] Eur J Neurosci. 1993 Feb 1;5(2):145-53 [8261096] Addiction. 1994 Nov;89(11):1559-63 [7841871] Brain Res. 1995 Mar 27;675(1-2):325-8 [7796146] Neuroscience. 1995 Apr;65(3):731-45 [7609872] Psychopharmacology (Berl). 1995 Jun;119(3):334-41 [7675970] Mol Neurobiol. 1995 Aug-Dec;11(1-3):1-19 [8561954] Psychopharmacology (Berl). 1996 Apr;124(4):306-14 [8739545] Curr Opin Neurobiol. 1996 Apr;6(2):243-51 [8725967] Psychopharmacology (Berl). 1996 May;125(1):13-22 [8724444] J Neurochem. 1996 Sep;67(3):1078-89 [8752115] Psychopharmacology (Berl). 1996 Jun;125(4):385-91 [8826544] J Neurosci. 1997 Apr 1;17(7):2605-14 [9065520] Neuroreport. 1997 Jul 7;8(9-10):2373-7 [9243643] Pharmacol Rev. 1997 Sep;49(3):231-52 [9311022] Science. 1997 Oct 3;278(5335):66-70 [9311929] Psychopharmacology (Berl). 1999 Mar;142(3):221-9 [10208313] Psychopharmacology (Berl). 1999 Mar;142(4):343-51 [10229058] Nature. 1999 Jul 22;400(6742):371-5 [10432116] Addiction. 1999 Mar;94(3):327-40 [10605857] Eur J Neurosci. 2000 Jan;12(1):292-302 [10651884] J Psychiatry Neurosci. 2000 Mar;25(2):125-36 [10740986] Eur Psychiatry. 2000 Mar;15(2):140-6 [10881212] J Pharmacol Exp Ther. 2000 Sep;294(3):1154-65 [10945872] Brain Res Brain Res Rev. 2000 Aug;33(1):13-33 [10967352] Eur J Pharmacol. 2000 Oct 27;407(1-2):47-51 [11050289] Curr Opin Investig Drugs. 2000 Sep;1(1):110-5 [11249586] Nat Rev Neurosci. 2001 Feb;2(2):119-28 [11252991] Eur J Pharmacol. 2001 Jul 20;424(2):85-90 [11476753] Xenobiotica. 2001 Aug-Sep;31(8-9):677-86 [11569533] Psychopharmacology (Berl). 2001 Dec;158(4):343-59 [11797055] Pharmacol Rev. 2002 Mar;54(1):1-42 [11870259] Biosci Rep. 2001 Jun;21(3):247-69 [11892993] Biol Psychiatry. 2002 May 15;51(10):775-87 [12007451] J Neurosci. 2002 Jul 1;22(13):5713-8 [12097523] J Neurosci. 2002 Nov 1;22(21):9595-603 [12417684] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational risk factors for the development of systemic lupus erythematosus. AN - 66946128; 15468355 AB - There have been few studies of occupational exposures and systemic lupus erythematosus (SLE). We examined the association between the risk of SLE and occupational exposures (mercury, solvents, and pesticides), specific jobs (ever worked in teaching, healthcare, and cosmetology), and working night or rotating shifts. Patients with recently diagnosed SLE (n = 265) were recruited through 4 university based and 30 community based rheumatology practices in North Carolina and South Carolina, USA. Controls (n = 355) were identified through driver's license records and were frequency matched to patients by age, sex, and state. Data collection included an in-person interview with detailed farming and work histories. Associations were seen with self-reported occupational exposure to mercury (OR 3.6, 95% CI 1.3, 10.0), mixing pesticides for agricultural work (OR 7.4, 95% CI 1.4, 40.0), and among dental workers (OR 7.1, 95% CI 2.2, 23.4). Although these associations were fairly strong and statistically significant, the prevalence of these exposures was very low and thus these estimates are based on a small number of exposed cases and controls. Weaker associations were seen between SLE and shift work (OR 1.6, 95% CI 0.99, 2.7) and among healthcare workers with patient contact (OR 1.7, 95% CI 0.99, 2.9). There was no association of SLE with use of solvents or among teachers or cosmetologists. This study reveals the potential contribution of occupational exposures to the development of SLE, and highlights some exposures and experiences that should be examined in other studies using more extensive exposure assessment techniques and in experimental studies of autoimmunity. JF - The Journal of rheumatology AU - Cooper, Glinda S AU - Parks, Christine G AU - Treadwell, Edward L AU - St Clair, E William AU - Gilkeson, Gary S AU - Dooley, Mary Anne AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina 27709, USA. copper1@niehs.nih.gov Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 1928 EP - 1933 VL - 31 IS - 10 SN - 0315-162X, 0315-162X KW - Solvents KW - 0 KW - Mercury KW - FXS1BY2PGL KW - Index Medicus KW - Mercury -- adverse effects KW - South Carolina KW - Risk Factors KW - Humans KW - North Carolina KW - Case-Control Studies KW - Solvents -- adverse effects KW - Lupus Erythematosus, Systemic -- immunology KW - Occupational Exposure -- adverse effects KW - Lupus Erythematosus, Systemic -- diagnosis KW - Lupus Erythematosus, Systemic -- physiopathology KW - Employment UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66946128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+rheumatology&rft.atitle=Occupational+risk+factors+for+the+development+of+systemic+lupus+erythematosus.&rft.au=Cooper%2C+Glinda+S%3BParks%2C+Christine+G%3BTreadwell%2C+Edward+L%3BSt+Clair%2C+E+William%3BGilkeson%2C+Gary+S%3BDooley%2C+Mary+Anne&rft.aulast=Cooper&rft.aufirst=Glinda&rft.date=2004-10-01&rft.volume=31&rft.issue=10&rft.spage=1928&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+rheumatology&rft.issn=0315162X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-07-21 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Delayed DMSO administration protects the kidney from mercuric chloride-induced injury. AN - 66939628; 15466269 AB - Reactive oxygen species are implicated as mediators of tissue damage in ischemic and toxic acute renal failure. Whereas many agents can inhibit renal ischemic injury, only hepatocyte growth factor, melatonin, N-acetylcysteine, and DMSO inhibit injury after mercuric chloride administration. Although it has been suggested that DMSO may chelate the mercuric ion, more recent studies suggest that it has anti-inflammatory and antioxidant effects. Acute renal failure was induced by 5 mg/kg subcutaneous injection of mercuric chloride in BALB/c mice. DMSO (3.8 ml/kg, 40% in PBS) or vehicle (PBS) was injected intraperitoneally at 0 and 24 h after mercuric chloride injection, or DMSO treatment was delayed 3 or 5 h. DMSO prevented increases in serum creatinine and tubular damage at 24 and 48 h. When DMSO treatment was delayed by 3 h, it was still beneficial; however, with a 5-h delay, the histology score and serum creatinine were not significantly decreased. DMSO partially prevented a mercuric chloride-induced decrease in glutathione peroxidase activity and completely prevented the transient decrease in superoxide dismutase activity. Neither mercuric chloride nor DMSO affected catalase activity significantly. For investigating possible effects of DMSO on cellular mercuric ion uptake, MDCK cells that were transfected with human organic anion transporter-1 were used. 203Hg uptake was inhibited 90% by N-acetylcysteine but only 5% by DMSO, indicating that the effect of DMSO is not related to chelating mercuric ion or inhibiting its uptake. It is concluded that DMSO acts in part as an antioxidant to inhibit mercuric chloride-induced acute renal injury. JF - Journal of the American Society of Nephrology : JASN AU - Jo, Sang-Kyung AU - Hu, Xuzhen AU - Yuen, Peter S T AU - Aslamkhan, Amy G AU - Pritchard, John B AU - Dear, James W AU - Star, Robert A AD - Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA. Y1 - 2004/10// PY - 2004 DA - October 2004 SP - 2648 EP - 2654 VL - 15 IS - 10 SN - 1046-6673, 1046-6673 KW - Mercuric Chloride KW - 53GH7MZT1R KW - Dimethyl Sulfoxide KW - YOW8V9698H KW - Index Medicus KW - Sensitivity and Specificity KW - Injections, Intraperitoneal KW - Animals KW - Kidney Function Tests KW - Probability KW - Reference Values KW - Drug Administration Schedule KW - Random Allocation KW - Disease Models, Animal KW - Mice KW - Biopsy, Needle KW - Mice, Inbred BALB C KW - Time Factors KW - Immunohistochemistry KW - Male KW - Dimethyl Sulfoxide -- pharmacology KW - Acute Kidney Injury -- pathology KW - Acute Kidney Injury -- chemically induced KW - Oxidative Stress -- drug effects KW - Acute Kidney Injury -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66939628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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+Society+of+Nephrology+%3A+JASN&rft.atitle=Delayed+DMSO+administration+protects+the+kidney+from+mercuric+chloride-induced+injury.&rft.au=Jo%2C+Sang-Kyung%3BHu%2C+Xuzhen%3BYuen%2C+Peter+S+T%3BAslamkhan%2C+Amy+G%3BPritchard%2C+John+B%3BDear%2C+James+W%3BStar%2C+Robert+A&rft.aulast=Jo&rft.aufirst=Sang-Kyung&rft.date=2004-10-01&rft.volume=15&rft.issue=10&rft.spage=2648&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Society+of+Nephrology+%3A+JASN&rft.issn=10466673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-27 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Am Soc Nephrol. 2004 Oct;15(10):2756-8 [15466282] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide, a mediator of inflammation, suppresses tumorigenesis. AN - 66936960; 15466171 AB - Inflammation influences the development of cancer. The nitric oxide synthase (NOS2) is induced by inflammatory cytokines, e.g., tumor necrosis factor alpha and interleukin 1beta, and produces nitric oxide (NO*), a critical mediator of the inflammatory response. Because p53 governs NO* production by transcriptionally transrepressing NOS2, we used a genetic strategy to determine whether NO* and p53 cooperatively regulate tumorigenesis. Lymphomas developed more rapidly in p53-/-NOS2-/- or p53-/-NOS2+/- mice than in p53-/-NOS2+/+ mice that were cross-bred into a >95% C57BL6 background and maintained in a pathogen-free condition. Likewise, sarcomas and lymphomas developed faster in p53+/-NOS2-/- or p53+/-NOS2+/- than in p53+/-NOS2+/+ mice. When compared with the double knockout mice, p53-/-NOS2+/+ mice showed a higher apoptotic index and a decreased proliferation index with an increased expression of death receptor ligands, CD95-L and tumor necrosis factor-related apoptosis-inducing ligand, and the cell cycle checkpoint protein, p21(waf1), in the spleen and thymus before tumor development. Furthermore, mice deficient in both p53 and NOS2 produced a high level of anti-inflammatory interleukin 10 when compared with p53-deficient mice. These studies provide genetic and mechanistic evidence that NO* can suppress tumorigenesis. JF - Cancer research AU - Hussain, S Perwez AU - Trivers, Glennwood E AU - Hofseth, Lorne J AU - He, Peijun AU - Shaikh, Irfan AU - Mechanic, Leah E AU - Doja, Saira AU - Jiang, Weidong AU - Subleski, Jeffrey AU - Shorts, Lynnette AU - Haines, Diana AU - Laubach, Victor E AU - Wiltrout, Robert H AU - Djurickovic, Draginja AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 2004/10/01/ PY - 2004 DA - 2004 Oct 01 SP - 6849 EP - 6853 VL - 64 IS - 19 SN - 0008-5472, 0008-5472 KW - Apoptosis Regulatory Proteins KW - 0 KW - Cdkn1a protein, mouse KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Inflammation Mediators KW - Ki-67 Antigen KW - Membrane Glycoproteins KW - TNF-Related Apoptosis-Inducing Ligand KW - Tnfsf10 protein, mouse KW - Tumor Necrosis Factor-alpha KW - Tumor Suppressor Protein p53 KW - Interleukin-10 KW - 130068-27-8 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 - Index Medicus KW - Animals KW - Ki-67 Antigen -- biosynthesis KW - Nitric Oxide Synthase -- deficiency KW - Cyclins -- biosynthesis KW - Apoptosis -- physiology KW - Disease Models, Animal KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Mice KW - Mice, Knockout KW - Membrane Glycoproteins -- biosynthesis KW - Nitric Oxide Synthase -- genetics KW - Mice, Inbred C57BL KW - Inbreeding KW - Interleukin-10 -- biosynthesis KW - Tumor Suppressor Protein p53 -- genetics KW - Nitric Oxide Synthase -- metabolism KW - Female KW - Male KW - Tumor Suppressor Protein p53 -- deficiency KW - Lymphoma, T-Cell -- pathology KW - Sarcoma, Experimental -- metabolism KW - Nitric Oxide -- metabolism KW - Sarcoma, Experimental -- pathology KW - Lymphoma, T-Cell -- enzymology KW - Lymphoma, T-Cell -- metabolism KW - Sarcoma, Experimental -- enzymology KW - Inflammation Mediators -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66936960?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Nitric+oxide%2C+a+mediator+of+inflammation%2C+suppresses+tumorigenesis.&rft.au=Hussain%2C+S+Perwez%3BTrivers%2C+Glennwood+E%3BHofseth%2C+Lorne+J%3BHe%2C+Peijun%3BShaikh%2C+Irfan%3BMechanic%2C+Leah+E%3BDoja%2C+Saira%3BJiang%2C+Weidong%3BSubleski%2C+Jeffrey%3BShorts%2C+Lynnette%3BHaines%2C+Diana%3BLaubach%2C+Victor+E%3BWiltrout%2C+Robert+H%3BDjurickovic%2C+Draginja%3BHarris%2C+Curtis+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=2004-10-01&rft.volume=64&rft.issue=19&rft.spage=6849&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 - 2004-11-16 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Schedule-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE glioblastoma xenografts. AN - 66935766; 15466170 AB - We have previously shown that topotecan, a topoisomerase I poison, inhibits hypoxia-inducible factor (HIF)-1alpha protein accumulation by a DNA damage-independent mechanism. Here, we report that daily administration of topotecan inhibits HIF-1alpha protein expression in U251-HRE glioblastoma xenografts. Concomitant with HIF-1alpha inhibition, topotecan caused a significant tumor growth inhibition associated with a marked decrease of angiogenesis and expression of HIF-1 target genes in tumor tissue. These results provide a compelling rationale for testing topotecan in clinical trials to target HIF-1 in cancer patients. JF - Cancer research AU - Rapisarda, Annamaria AU - Zalek, Jessica AU - Hollingshead, Melinda AU - Braunschweig, Till AU - Uranchimeg, Badarch AU - Bonomi, Carrie A AU - Borgel, Suzanne D AU - Carter, John P AU - Hewitt, Stephen M AU - Shoemaker, Robert H AU - Melillo, Giovanni AD - Science Applications International Corporation-Frederick, Inc., National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. melillog@ncifcrd.gov Y1 - 2004/10/01/ PY - 2004 DA - 2004 Oct 01 SP - 6845 EP - 6848 VL - 64 IS - 19 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - HIF1A protein, human KW - Hypoxia-Inducible Factor 1, alpha Subunit KW - Topoisomerase I Inhibitors KW - Transcription Factors KW - Topotecan KW - 7M7YKX2N15 KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Humans KW - Cell Division -- drug effects KW - Mice, Nude KW - Cell Line, Tumor KW - Mice KW - Luciferases -- biosynthesis KW - Luciferases -- antagonists & inhibitors KW - Xenograft Model Antitumor Assays KW - Enzyme Inhibitors -- pharmacology KW - Luciferases -- genetics KW - Female KW - Neovascularization, Pathologic -- drug therapy KW - Glioblastoma -- blood supply KW - Transcription Factors -- antagonists & inhibitors KW - Antineoplastic Agents -- administration & dosage KW - Glioblastoma -- pathology KW - Glioblastoma -- metabolism KW - Topotecan -- administration & dosage KW - Neovascularization, Pathologic -- metabolism KW - Glioblastoma -- drug therapy KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66935766?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Schedule-dependent+inhibition+of+hypoxia-inducible+factor-1alpha+protein+accumulation%2C+angiogenesis%2C+and+tumor+growth+by+topotecan+in+U251-HRE+glioblastoma+xenografts.&rft.au=Rapisarda%2C+Annamaria%3BZalek%2C+Jessica%3BHollingshead%2C+Melinda%3BBraunschweig%2C+Till%3BUranchimeg%2C+Badarch%3BBonomi%2C+Carrie+A%3BBorgel%2C+Suzanne+D%3BCarter%2C+John+P%3BHewitt%2C+Stephen+M%3BShoemaker%2C+Robert+H%3BMelillo%2C+Giovanni&rft.aulast=Rapisarda&rft.aufirst=Annamaria&rft.date=2004-10-01&rft.volume=64&rft.issue=19&rft.spage=6845&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 - 2004-11-16 N1 - Date created - 2004-10-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Warfarin and aspirin use and the predictors of major bleeding complications in atrial fibrillation (the Framingham Heart Study). AN - 66935561; 15464686 AB - The Framingham Heart Study records of participants with atrial fibrillation (AF) during 1980 and 1994 were retrospectively reviewed to determine the prevalence of warfarin and aspirin use in AF. Anticoagulant use increased significantly in the 393 men and women (mean ages 72.5 and 79.0 years, respectively) who developed AF over the observation period: aspirin use increased from 14% to 39% in men and from 19% to 33% in women, and warfarin use increased from 10% to 39% in men and from 17% to 38% in women. There were no significant gender differences in anticoagulant use (p = 0.61), but participants using warfarin were younger. A total of 65 participants (17%) had major bleeding complications 64 microg/ml) clinical isolates from patients with refractory esophageal candidiasis. Antifungal therapy was administered for 7 days. Study groups consisted of untreated controls; animals receiving PLD-118 at 4, 10, 25, or 50 mg/kg of body weight/day via intravenous (i.v.) twice daily (BID) injections; animals receiving FLC at 2 mg/kg/day via i.v. BID injections; and animals receiving desoxycholate amphotericin B (DAMB) i.v. at 0.5 mg/kg/day. PLD-118- and DAMB-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, and esophagus in comparison to untreated controls (P 0.05). These data show that widening the range of applied stimuli to carotid sinus baroreceptors does not induce a change in FBF. However, the small transient changes reported previously cannot be discounted. JF - European Journal of Applied Physiology AU - Howden, R AU - Lightfoot, J T AU - Turner, MJ AU - Brown, S J AU - Swaine, IL AD - National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Building 101, MD D2-01, Research Triangle Park, NC 27709, USA, howden@niehs.nih.gov Y1 - 2004/10// PY - 2004 DA - Oct 2004 SP - 124 EP - 129 VL - 93 IS - 1-2 SN - 1439-6319, 1439-6319 KW - Physical Education Index KW - Reflexes KW - Blood flow KW - Stimuli KW - Stress KW - Neck KW - Arms KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17485038?accountid=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=European+Journal+of+Applied+Physiology&rft.atitle=A+wide+range+of+baroreflex+stimulation+does+not+alter+forearm+blood+flow&rft.au=Howden%2C+R%3BLightfoot%2C+J+T%3BTurner%2C+MJ%3BBrown%2C+S+J%3BSwaine%2C+IL&rft.aulast=Howden&rft.aufirst=R&rft.date=2004-10-01&rft.volume=93&rft.issue=1-2&rft.spage=124&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Applied+Physiology&rft.issn=14396319&rft_id=info:doi/10.1007%2Fs00421-004-1181-7 LA - English DB - Physical Education Index N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neck; Reflexes; Stress; Stimuli; Arms; Blood flow DO - http://dx.doi.org/10.1007/s00421-004-1181-7 ER - TY - JOUR T1 - Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase AN - 17438570; 6589077 AB - The contributing role of environmental factors to the development of Parkinson's disease has become increasingly evident. We report that mesencephalic neuron-glia cultures treated with diesel exhaust particles (DEP; 0.22 mu M) (5-50 mu g/ml) resulted in a dose-dependent decrease in dopaminergic (DA) neurons, as determined by DA-uptake assay and tyrosine-hydroxylase immunocytochemistry (ICC). The selective toxicity of DEP for DA neurons was demonstrated by the lack of DEP effect on both GABA uptake and Neu-N immunoreactive cell number. The critical role of microglia was demonstrated by the failure of neuron-enriched cultures to exhibit DEP-induced DA neurotoxicity, where DEP-induced DA neuron death was reinstated with the addition of microglia to neuron-enriched cultures. OX-42 ICC staining of DEP treated neuron-glia cultures revealed changes in microglia morphology indicative of activation. Intracellular reactive oxygen species and superoxide were produced from enriched-microglia cultures in response to DEP. Neuron-glia cultures from NADPH oxidase deficient (PHOX super(-/-)) mice were insensitive to DEP neurotoxicity when compared with control mice (PHOX super(+/+)). Cytochalasin D inhibited DEP-induced superoxide production in enriched-microglia cultures, implying that DEP must be phagocytized by microglia to produce superoxide. Together, these in vitro data indicate that DEP selectively damages DA neurons through the phagocytic activation of microglial NADPH oxidase and consequent oxidative insult. JF - FASEB Journal AU - Block, M L AU - Wu, X AU - Pei, Z AU - Li, G AU - Wang, T AU - Qin, L AU - Wilson, B AU - Yang, J AU - Hong, J S AU - Veronesi, B Y1 - 2004/10// PY - 2004 DA - Oct 2004 SP - 1618 EP - 1620 PB - Federation of American Societies for Experimental Biology VL - 18 IS - 13 SN - 0892-6638, 0892-6638 KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - Cell number KW - Parkinson's disease KW - gamma -Aminobutyric acid KW - Microglia KW - Environmental factors KW - Exhausts KW - Neurodegenerative diseases KW - Movement disorders KW - cytochalasin D KW - Dopamine KW - Reactive oxygen species KW - Superoxide KW - Neurons KW - Neurotoxicity KW - Diesel KW - Phagocytosis KW - NADPH oxidase KW - X 24155:Biochemistry KW - N3 11011:Motor systems and movement disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17438570?accountid=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=Nanometer+size+diesel+exhaust+particles+are+selectively+toxic+to+dopaminergic+neurons%3A+the+role+of+microglia%2C+phagocytosis%2C+and+NADPH+oxidase&rft.au=Block%2C+M+L%3BWu%2C+X%3BPei%2C+Z%3BLi%2C+G%3BWang%2C+T%3BQin%2C+L%3BWilson%2C+B%3BYang%2C+J%3BHong%2C+J+S%3BVeronesi%2C+B&rft.aulast=Block&rft.aufirst=M&rft.date=2004-10-01&rft.volume=18&rft.issue=13&rft.spage=1618&rft.isbn=&rft.btitle=&rft.title=FASEB+Journal&rft.issn=08926638&rft_id=info:doi/10.1096%2Ffj.04-1945fje LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-04-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - Cell number; Parkinson's disease; gamma -Aminobutyric acid; Microglia; Environmental factors; Exhausts; Neurodegenerative diseases; Dopamine; cytochalasin D; Movement disorders; Reactive oxygen species; Neurons; Superoxide; Neurotoxicity; Diesel; Phagocytosis; NADPH oxidase DO - http://dx.doi.org/10.1096/fj.04-1945fje ER - TY - JOUR T1 - Pharmacokinetics of a triarylmethyl-type paramagnetic spin probe used in EPR oximetry AN - 17388652; 6495186 AB - The paramagnetic spin probe Oxo63 is used in oximetric imaging studies based on electron paramagnetic resonance (EPR) methods by monitoring the oxygen-dependent line-width while minimizing the contributions from self-broadening seen at high probe concentrations. Therefore, it is necessary to determine a suitable dose of Oxo63 for EPR-based oxygen mapping where the self-broadening effects are minimized while signal intensity adequate for imaging can be realized. A constant tissue concentration of spin probe would be useful to image a subject and assess changes in pO sub(2) over time; accumulation or elimination of the compound in specific anatomical regions could translate to and be mistaken for changes in local pO sub(2), especially in OMRI-based oximetry. The in vivo pharmacokinetics of the spin probe, Oxo63, after bolus and/or continuous intravenous infusion was investigated in mice using a novel approach with X-band EPR spectroscopy. The results show that the half-life in blood was 17-21 min and the clearance by excretion was 0.033-0.040/min. Continuous infusion following a bolus injection of the probe was found to be effective to obtain stable plasma concentration as well as image intensity to permit reliable pO sub(2) estimates. JF - Magnetic Resonance in Medicine AU - Matsumoto, Ken-Ichiro AU - English, Sean AU - Yoo, John AU - Yamada, Ken-Ichi AU - Devasahayam, Nallathamby AU - Cook, John A AU - Mitchell, James B AU - Subramanian, Sankaran AU - Krishna, Murali C AD - Building 10, Room B3B69, NIH, Bethesda, MD 20892-1002, USA, murali@helix.nih.gov Y1 - 2004/10// PY - 2004 DA - Oct 2004 SP - 885 EP - 892 PB - John Wiley & Sons, Ltd. VL - 52 IS - 4 SN - 0740-3194, 0740-3194 KW - triarylmethyl KW - Biotechnology and Bioengineering Abstracts; Bioengineering Abstracts KW - E.S.R. KW - Blood KW - Oxygen KW - Intravenous administration KW - Excretion KW - N.M.R. KW - Spectroscopy KW - imaging KW - Spin probes KW - Pharmacokinetics KW - W4 150:Medical Imaging KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17388652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Magnetic+Resonance+in+Medicine&rft.atitle=Pharmacokinetics+of+a+triarylmethyl-type+paramagnetic+spin+probe+used+in+EPR+oximetry&rft.au=Matsumoto%2C+Ken-Ichiro%3BEnglish%2C+Sean%3BYoo%2C+John%3BYamada%2C+Ken-Ichi%3BDevasahayam%2C+Nallathamby%3BCook%2C+John+A%3BMitchell%2C+James+B%3BSubramanian%2C+Sankaran%3BKrishna%2C+Murali+C&rft.aulast=Matsumoto&rft.aufirst=Ken-Ichiro&rft.date=2004-10-01&rft.volume=52&rft.issue=4&rft.spage=885&rft.isbn=&rft.btitle=&rft.title=Magnetic+Resonance+in+Medicine&rft.issn=07403194&rft_id=info:doi/10.1002%2Fmrm.20222 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-05-01 N1 - Last updated - 2015-03-25 N1 - SubjectsTermNotLitGenreText - E.S.R.; Oxygen; Blood; Intravenous administration; N.M.R.; Excretion; Spectroscopy; imaging; Pharmacokinetics; Spin probes DO - http://dx.doi.org/10.1002/mrm.20222 ER - TY - JOUR T1 - Effects of habitual exercise on sleep habits and sleep health in middle-aged and older Japanese women AN - 17316772; 6199363 AB - The present study performed a cross-sectional survey to investigate sleep habits and sleep health in Japanese women aged 40 to 69 years with and without a habit of exercise. A standardized questionnaire evaluating sleep was administered to two subject groups. One was the "exercise group" who habitually performed aerobic exercise at mild to moderate intensity with a frequency of =~. 2 times/week and duration of =~. 30 minutes/one session (n = 207). The other was the age-matched "non-exercise group" who had no exercise habit (n = 567). Two-way ANOVA was employed for comparing the two subject groups and examining the effects of exercise on aging. Regarding sleep habits, as bed time significantly advanced with advancing age, sleep habits (bed time, waking time and sleep duration) were significantly more regular in the exercise group than in the non-exercise group. Concerning independent sleep health risk factors consisting of sleep initiation, sleep maintenance, sleep apnea, parasomnia, and waking-up, the factor score for sleep maintenance significantly deteriorated with advancing age; and was significantly better in the exercise group than in the non-exercise group. These results suggest that an exercise habit may improve sleep health in middle-aged and older Japanese women among which a higher prevalence of sleep problems has been reported. JF - Japanese Journal of Physical Fitness and Sports Medicine AU - Mizuno, K AU - Kunii, M AU - Seita, T AU - Ono, S AU - Komada, Y AU - Shirakawa, S AD - Geriatric Mental Health, National Institute of Mental Health Y1 - 2004/10// PY - 2004 DA - Oct 2004 SP - 527 EP - 536 VL - 53 IS - 5 SN - 0039-906X, 0039-906X KW - Physical Education Index KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17316772?accountid=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=unknown&rft.jtitle=S%C3%A9quences&rft.atitle=Mulan.+Esquisse.&rft.au=V%C3%A9zina%2C+Alain&rft.aulast=V%C3%A9zina&rft.aufirst=Alain&rft.date=1998-09-01&rft.volume=&rft.issue=198&rft.spage=50&rft.isbn=&rft.btitle=&rft.title=S%C3%A9quences&rft.issn=00372412&rft_id=info:doi/ LA - English DB - Physical Education Index N1 - Date revised - 2006-01-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Scale-free networks versus evolutionary drift AN - 17304102; 6096325 AB - Recent studies of properties of various biological networks revealed that many of them display scale-free characteristics. Since the theory of scale-free networks is applicable to evolving networks, one can hope that it provides not only a model of a biological network in its current state but also sheds some insight into the evolution of the network. In this work, we investigate the probability distributions and scaling properties underlying some models for biological networks and protein domain evolution. The analysis of evolutionary models for domain similarity networks indicates that models which include evolutionary drift are typically not scale free. Instead they adhere quite closely to the Yule distribution. This finding indicates that the direct applicability of scale-free models in understanding the evolution of biological network may not be as wide as it has been hoped for. JF - Computational Biology and Chemistry AU - Przytycka, T M AU - Yu, Y-K AD - NCBI/NLM/NIH 8600 Rockville Pike, Bethesda, MD 20894, USA, przytyck@ncbi.nlm.nih.gov Y1 - 2004/10// PY - 2004 DA - Oct 2004 SP - 257 EP - 264 PB - Elsevier Science Ltd., The Boulevard Langford Lane Kidlington Oxford OX5 1GB UK, [mailto:usinfo-f@elsevier.com], [URL:http://www.elsevier.nl] VL - 28 IS - 4 SN - 1476-9271, 1476-9271 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/17304102?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Computational+Biology+and+Chemistry&rft.atitle=Scale-free+networks+versus+evolutionary+drift&rft.au=Przytycka%2C+T+M%3BYu%2C+Y-K&rft.aulast=Przytycka&rft.aufirst=T&rft.date=2004-10-01&rft.volume=28&rft.issue=4&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Computational+Biology+and+Chemistry&rft.issn=14769271&rft_id=info:doi/10.1016%2Fj.compbiolchem.2004.07.001 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-06-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/j.compbiolchem.2004.07.001 ER - TY - JOUR T1 - Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. AN - 66935870; 15459300 AB - Patients with persistent fever and neutropenia often receive empirical therapy with conventional or liposomal amphotericin B for the prevention and early treatment of invasive fungal infections. Caspofungin, a member of the new echinocandin class of compounds, may be an effective alternative that is better tolerated than amphotericin B. In this randomized, double-blind, multinational trial, we assessed the efficacy and safety of caspofungin as compared with liposomal amphotericin B as empirical antifungal therapy. At study entry, patients were stratified according to risk and according to whether they had previously received antifungal prophylaxis. A successful outcome was defined as the fulfillment of all components of a five-part composite end point. Efficacy was evaluated in 1095 patients (556 receiving caspofungin and 539 receiving liposomal amphotericin B). After adjustment for strata, the overall success rates were 33.9 percent for caspofungin and 33.7 percent for liposomal amphotericin B (95.2 percent confidence interval for the difference, -5.6 to 6.0 percent), fulfilling statistical criteria for the noninferiority of caspofungin. Among patients with baseline fungal infections, a higher proportion of those treated with caspofungin had a successful outcome (51.9 percent vs. 25.9 percent, P=0.04). The proportion of patients who survived at least seven days after therapy was greater in the caspofungin group (92.6 percent vs. 89.2 percent, P=0.05). Premature study discontinuation occurred less often in the caspofungin group than in the amphotericin B group (10.3 percent vs. 14.5 percent, P=0.03). The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in the two groups. Fewer patients who received caspofungin sustained a nephrotoxic effect (2.6 percent vs. 11.5 percent, P<0.001), an infusion-related event (35.1 percent vs. 51.6 percent, P<0.001), or a drug-related adverse event or discontinued therapy because of drug-related adverse events. Caspofungin is as effective as and generally better tolerated than liposomal amphotericin B when given as empirical antifungal therapy in patients with persistent fever and neutropenia. Copyright 2004 Massachusetts Medical Society JF - The New England journal of medicine AU - Walsh, Thomas J AU - Teppler, Hedy AU - Donowitz, Gerald R AU - Maertens, Johan A AU - Baden, Lindsey R AU - Dmoszynska, Anna AU - Cornely, Oliver A AU - Bourque, Michael R AU - Lupinacci, Robert J AU - Sable, Carole A AU - dePauw, Ben E AD - National Cancer Institute, National Institutes of Health, Bethesda, Md 20892, USA. Y1 - 2004/09/30/ PY - 2004 DA - 2004 Sep 30 SP - 1391 EP - 1402 VL - 351 IS - 14 KW - Antifungal Agents KW - 0 KW - Echinocandins KW - Lipopeptides KW - Liposomes KW - Peptides KW - Peptides, Cyclic KW - Amphotericin B KW - 7XU7A7DROE KW - caspofungin KW - F0XDI6ZL63 KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Neoplasms -- mortality KW - Neutropenia -- etiology KW - Humans KW - Aged KW - Neoplasms -- therapy KW - Fever -- etiology KW - Neoplasms -- complications KW - Survival Rate KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Kidney Diseases -- chemically induced KW - Antifungal Agents -- adverse effects KW - Mycoses -- prevention & control KW - Amphotericin B -- adverse effects KW - Amphotericin B -- administration & dosage KW - Mycoses -- drug therapy KW - Peptides -- adverse effects KW - Mycoses -- etiology KW - Peptides -- therapeutic use KW - Amphotericin B -- therapeutic use KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66935870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=Caspofungin+versus+liposomal+amphotericin+B+for+empirical+antifungal+therapy+in+patients+with+persistent+fever+and+neutropenia.&rft.au=Walsh%2C+Thomas+J%3BTeppler%2C+Hedy%3BDonowitz%2C+Gerald+R%3BMaertens%2C+Johan+A%3BBaden%2C+Lindsey+R%3BDmoszynska%2C+Anna%3BCornely%2C+Oliver+A%3BBourque%2C+Michael+R%3BLupinacci%2C+Robert+J%3BSable%2C+Carole+A%3BdePauw%2C+Ben+E&rft.aulast=Walsh&rft.aufirst=Thomas&rft.date=2004-09-30&rft.volume=351&rft.issue=14&rft.spage=1391&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 - 2004-10-06 N1 - Date created - 2004-10-01 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 2005 Jan 27;352(4):410-4; author reply 410-4 [15675094] N Engl J Med. 2005 Jan 27;352(4):410-4; author reply 410-4 [15675093] N Engl J Med. 2005 Jan 27;352(4):410-4; author reply 410-4 [15675091] N Engl J Med. 2005 Jan 27;352(4):410-4; author reply 410-4 [15673808] N Engl J Med. 2005 Jan 27;352(4):410-4; author reply 410-4 [15675092] N Engl J Med. 2004 Sep 30;351(14):1445-7 [15459307] ACP J Club. 2005 Mar-Apr;142(2):33 [15739980] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic polymorphisms in three Iranian populations with different risks of esophageal cancer, an ecologic comparison. AN - 66814269; 15327835 AB - The age-standardized incidence of esophageal cancer (EC) varies from 3 to >100/100,000 per year in different provinces of Iran. This striking variation of incidence is associated with differences in ethnic backgrounds, raising the possibility that genetic factors are involved in the pathogenesis of EC. We compared the frequencies of polymorphisms in ten genes that have been hypothesized to have a role in risk of EC (CYP1A1, CYP2A6, CYP2E1, GSTM1, GSTP1, GSTT1, ADH2, ADH3, ALDH2, and O6-MGMT) among three Iranian ethnic groups with highly varying rates of EC. These three groups included high-risk Turkomans, medium-risk Turks, and low-risk Zoroastrian Persians. Compared to Zoroastrians, Turkomans had higher frequency of four alleles that are speculated to favor carcinogenesis (CYP1A1 m1, CYP1A1 m2, CYP2A6*9, and ADH2*1); these results are consistent with an influence of these allele variants on the population risk of EC. However, none of these four alleles had a high enough prevalence in Turkomans to explain the high rates of EC in this group. Three of these four alleles (CYP1A1 m1, CYP1A1 m2, CYP2A6*9) were less frequent among Turkomans than in some Asian populations with lower risks of EC. We conclude that it is unlikely that variations in these polymorphic genes are major contributors to the high incidence of EC among Turkomans in Iran. JF - Cancer letters AU - Sepehr, Alireza AU - Kamangar, Farin AU - Abnet, Christian C AU - Fahimi, Saman AU - Pourshams, Akram AU - Poustchi, Hossein AU - Zeinali, Sirous AU - Sotoudeh, Masood AU - Islami, Farhad AU - Nasrollahzadeh, Dariush AU - Malekzadeh, Reza AU - Taylor, Philip R AU - Dawsey, Sanford M AD - The US National Cancer Institute, Bethesda, MD, USA. Y1 - 2004/09/30/ PY - 2004 DA - 2004 Sep 30 SP - 195 EP - 202 VL - 213 IS - 2 SN - 0304-3835, 0304-3835 KW - Enzymes KW - 0 KW - Index Medicus KW - Ecology KW - Risk Factors KW - Iran -- ethnology KW - Iran -- epidemiology KW - Humans KW - Asia -- epidemiology KW - Incidence KW - Enzymes -- genetics KW - Genetics, Population KW - Polymorphism, Genetic KW - Esophageal Neoplasms -- ethnology KW - Esophageal Neoplasms -- genetics KW - Genetic Predisposition to Disease KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66814269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+polymorphisms+in+three+Iranian+populations+with+different+risks+of+esophageal+cancer%2C+an+ecologic+comparison.&rft.au=Sepehr%2C+Alireza%3BKamangar%2C+Farin%3BAbnet%2C+Christian+C%3BFahimi%2C+Saman%3BPourshams%2C+Akram%3BPoustchi%2C+Hossein%3BZeinali%2C+Sirous%3BSotoudeh%2C+Masood%3BIslami%2C+Farhad%3BNasrollahzadeh%2C+Dariush%3BMalekzadeh%2C+Reza%3BTaylor%2C+Philip+R%3BDawsey%2C+Sanford+M&rft.aulast=Sepehr&rft.aufirst=Alireza&rft.date=2004-09-30&rft.volume=213&rft.issue=2&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-01 N1 - Date created - 2004-08-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A distal region in the interferon-gamma gene is a site of epigenetic remodeling and transcriptional regulation by interleukin-2. AN - 66891741; 15271977 AB - Interferon-gamma (IFN-gamma) is a multifunctional cytokine that defines the development of Th1 cells and is critical for host defense against intracellular pathogens. IL-2 is another key immunoregulatory cytokine that is involved in T helper differentiation and is known to induce IFN-gamma expression in natural killer (NK) and T cells. Despite concerted efforts to identify the one or more transcriptional control mechanisms by which IL-2 induces IFN-gamma mRNA expression, no such genomic regulatory regions have been described. We have identified a DNase I hypersensitivity site approximately 3.5-4.0 kb upstream of the transcriptional start site. Using chromatin immunoprecipitation assays we found constitutive histone H3 acetylation in this distal region in primary human NK cells, which is enhanced by IL-2 treatment. This distal region is also preferentially acetylated on histones H3 and H4 in primary Th1 cells as compared with Th2 cells. Within this distal region we found a Stat5-like motif, and in vitro DNA binding assays as well as in vivo chromosomal immunoprecipitation assays showed IL-2-induced binding of both Stat5a and Stat5b to this distal element in the IFNG gene. We examined the function of this Stat5-binding motif by transfecting human peripheral blood mononuclear cells with -3.6 kb of IFNG-luciferase constructs and found that phorbol 12-myristate 13-acetate/ionomycin-induced transcription was augmented by IL-2 treatment. The effect of IL-2 was lost when the Stat5 motif was disrupted. These data led us to conclude that this distal region serves as both a target of chromatin remodeling in the IFNG locus as well as an IL-2-induced transcriptional enhancer that binds Stat5 proteins. Copyright 2004 American Society for Biochemistry and Molecular Biology, Inc. JF - The Journal of biological chemistry AU - Bream, Jay H AU - Hodge, Deborah L AU - Gonsky, Rivkah AU - Spolski, Rosanne AU - Leonard, Warren J AU - Krebs, Stephanie AU - Targan, Stephan AU - Morinobu, Akio AU - O'Shea, John J AU - Young, Howard A AD - Lymphocyte and Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (NIH), Bethesda, Maryland 20892-1820, USA. jbream@jhsph.edu Y1 - 2004/09/24/ PY - 2004 DA - 2004 Sep 24 SP - 41249 EP - 41257 VL - 279 IS - 39 SN - 0021-9258, 0021-9258 KW - Chromatin KW - 0 KW - DNA-Binding Proteins KW - Histones KW - Interleukin-2 KW - Milk Proteins KW - RNA, Messenger KW - STAT5 Transcription Factor KW - STAT5A protein, human KW - STAT5B protein, human KW - Trans-Activators KW - Tumor Suppressor Proteins KW - Interleukin-12 KW - 187348-17-0 KW - Ionomycin KW - 56092-81-0 KW - Interferon-gamma KW - 82115-62-6 KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Trans-Activators -- metabolism KW - Chromatin -- metabolism KW - Cell Nucleus -- metabolism KW - Humans KW - Transcription, Genetic KW - Ionomycin -- pharmacology KW - Th1 Cells -- metabolism KW - Th2 Cells -- metabolism KW - Promoter Regions, Genetic KW - Amino Acid Motifs KW - Genes, Reporter KW - DNA-Binding Proteins -- metabolism KW - Cell Division KW - Milk Proteins -- metabolism KW - Precipitin Tests KW - Cloning, Molecular KW - Interleukin-12 -- metabolism KW - RNA, Messenger -- metabolism KW - Transfection KW - Deoxyribonuclease I -- metabolism KW - Histones -- metabolism KW - Enhancer Elements, Genetic KW - Leukocytes, Mononuclear -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line KW - Interferon-gamma -- genetics KW - Interleukin-2 -- metabolism KW - Interferon-gamma -- metabolism KW - Gene Expression Regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66891741?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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=A+distal+region+in+the+interferon-gamma+gene+is+a+site+of+epigenetic+remodeling+and+transcriptional+regulation+by+interleukin-2.&rft.au=Bream%2C+Jay+H%3BHodge%2C+Deborah+L%3BGonsky%2C+Rivkah%3BSpolski%2C+Rosanne%3BLeonard%2C+Warren+J%3BKrebs%2C+Stephanie%3BTargan%2C+Stephan%3BMorinobu%2C+Akio%3BO%27Shea%2C+John+J%3BYoung%2C+Howard+A&rft.aulast=Bream&rft.aufirst=Jay&rft.date=2004-09-24&rft.volume=279&rft.issue=39&rft.spage=41249&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 - 2004-10-26 N1 - Date created - 2004-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Depletion of Intracellular Ascorbate by the Carcinogenic Metals Nickel and Cobalt Results in the Induction of Hypoxic Stress AN - 19823174; 6030031 AB - Exposure of cells to carcinogenic compounds of nickel(II) and cobalt(II) causes activation of the HIF-1 transcription factor and up-regulates a battery of hypoxia-inducible genes. However, the mechanism of HIF-1 activation by these metals is not known. It was shown recently that hydroxylation of prolines in the HIFalpha subunit of HIF-1 is required for its binding with the von Hippel-Lindau tumor suppressor protein and the subsequent proteasomal destruction. Here we show that responsible prolyl hydroxylases are targets for both nickel(II) and cobalt(II) because degradation of a reporter protein containing the oxygen- dependent degradation domain (Pro-402/564) of HIFalpha was abolished in a von Hippel-Lindau-dependent manner in cells exposed to nickel(II) or cobalt(II). The enzymatic activity of prolyl hydroxylases depends on iron as the activating metal, 2-oxoglutarate as a co-substrate, and ascorbic acid as a cofactor. Hydroxylase activity can be impaired by the depletion of any of these factors. We found that exposure of cells to nickel(II) or cobalt(II) did not affect the level of intracellular iron. Instead, nickel(II) or cobalt(II) exposure greatly depleted intracellular ascorbate. Co-exposure of cells to metals and ascorbate resulted in the increase of intracellular ascorbate and reversed both metal- induced stabilization of HIF-1alpha and HIF-1-dependent gene transcription. Because ascorbate is essential for maintaining iron in prolyl hydroxylases in the active iron(II) state, we suggest that the observed depletion of ascorbate by nickel(II) or cobalt(II) favors iron oxidation and thus inactivation of the enzyme. JF - Journal of Biological Chemistry AU - Salnikow, Konstantin AU - Donald, Steven P AU - Bruick, Richard K AU - Zhitkovich, Anatoly AU - Phang, James M AU - Kasprzak, Kazimierz S AD - NCI-Frederick, National Institutes of Health, Frederick, Maryland Y1 - 2004/09/24/ PY - 2004 DA - 2004 Sep 24 SP - 40337 EP - 40344 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 - 279 IS - 39 SN - 0021-9258, 0021-9258 KW - Toxicology Abstracts KW - Tumor suppressor genes KW - Proline KW - prolyl hydroxylase KW - Heavy metals KW - Nickel KW - proteasomes KW - Stress KW - Hypoxia-inducible factor 1 alpha KW - VHL protein KW - Hydroxylation KW - Ascorbic acid KW - Cofactors KW - Transcription factors KW - Cobalt KW - Hypoxia KW - Oxidation KW - Enzymatic activity KW - Hydroxylase KW - Iron KW - alpha -Ketoglutaric acid KW - X 24360:Metals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19823174?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Depletion+of+Intracellular+Ascorbate+by+the+Carcinogenic+Metals+Nickel+and+Cobalt+Results+in+the+Induction+of+Hypoxic+Stress&rft.au=Salnikow%2C+Konstantin%3BDonald%2C+Steven+P%3BBruick%2C+Richard+K%3BZhitkovich%2C+Anatoly%3BPhang%2C+James+M%3BKasprzak%2C+Kazimierz+S&rft.aulast=Salnikow&rft.aufirst=Konstantin&rft.date=2004-09-24&rft.volume=279&rft.issue=39&rft.spage=40337&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Tumor suppressor genes; Proline; Heavy metals; prolyl hydroxylase; Nickel; proteasomes; Stress; VHL protein; Hypoxia-inducible factor 1 alpha; Ascorbic acid; Hydroxylation; Cofactors; Hypoxia; Cobalt; Transcription factors; Oxidation; Enzymatic activity; Hydroxylase; alpha -Ketoglutaric acid; Iron ER - TY - JOUR T1 - Conformationally constrained analogues of diacylglycerol (DAG). 23. Hydrophobic ligand-protein interactions versus ligand-lipid interactions of DAG-lactones with protein kinase C (PK-C). AN - 66883149; 15369389 AB - The constrained glycerol backbone of DAG-lactones, when combined with highly branched alkyl chains, has engendered a series of DAG-lactone ligands capable of binding protein kinase C (PK-C) with affinities that approximate those of phorbol esters. These branched chains not only appear to be involved in making important hydrophobic contacts with the protein (specific interactions) but also provide adequate lipophilicity to facilitate partitioning into the lipid-rich membrane environment (nonspecific interactions). With the idea of minimizing the nonspecific interactions without reducing lipophilicity, the present work explores the strategy of relocating lipophilicity from the side chain to the lactone "core". Such a transfer of lipophilicity, exemplified by compounds 1 and 3, was conceived to allow the new hydrophobic groups on the lactone to engage in specific hydrophobic contacts inside the binding pocket without any expectation of interfering with the hydrogen-bonding network of the DAG-lactone pharmacophore. Surprisingly, both (E)-3 and (Z)-3 showed a significant decrease in binding affinity. From the molecular docking studies performed with the new ligands, we conclude that the binding pocket of the C1 domain of PK-C is sterically restricted and prevents the methyl groups at the C-3 position of the lactone from engaging in productive hydrophobic contacts with the receptor. JF - Journal of medicinal chemistry AU - Tamamura, Hirokazu AU - Sigano, Dina M AU - Lewin, Nancy E AU - Peach, Megan L AU - Nicklaus, Marc C AU - Blumberg, Peter M AU - Marquez, Victor E AD - Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Building 376, Room 104, Frederick, Maryland 21702, USA. Y1 - 2004/09/23/ PY - 2004 DA - 2004 Sep 23 SP - 4858 EP - 4864 VL - 47 IS - 20 SN - 0022-2623, 0022-2623 KW - 1,2-diacylglycerol KW - 0 KW - Diglycerides KW - Lactones KW - Ligands KW - Lipids KW - Phorbol Esters KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Phorbol Esters -- chemistry KW - Hydrophobic and Hydrophilic Interactions KW - Phorbol Esters -- metabolism KW - Models, Molecular KW - Lipids -- chemistry KW - Molecular Conformation KW - Protein Binding KW - Hydrogen Bonding KW - Structure-Activity Relationship KW - Protein Conformation KW - Binding Sites KW - Protein Kinase C -- metabolism KW - Diglycerides -- chemistry KW - Lactones -- chemistry KW - Protein Kinase C -- chemistry KW - Lipid Metabolism KW - Lactones -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66883149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Conformationally+constrained+analogues+of+diacylglycerol+%28DAG%29.+23.+Hydrophobic+ligand-protein+interactions+versus+ligand-lipid+interactions+of+DAG-lactones+with+protein+kinase+C+%28PK-C%29.&rft.au=Tamamura%2C+Hirokazu%3BSigano%2C+Dina+M%3BLewin%2C+Nancy+E%3BPeach%2C+Megan+L%3BNicklaus%2C+Marc+C%3BBlumberg%2C+Peter+M%3BMarquez%2C+Victor+E&rft.aulast=Tamamura&rft.aufirst=Hirokazu&rft.date=2004-09-23&rft.volume=47&rft.issue=20&rft.spage=4858&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 - 2004-11-01 N1 - Date created - 2004-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alternative modalities of adenovirus-mediated gene expression in hippocampal neurons cultured on microisland substrate. AN - 66851459; 15351453 AB - Previously, we have used CsCl gradient-purified recombinant adenovirus (AdV) to successfully transfer genes into hippocampal neurons cultured on microisland substrate. Here, we report that purification of AdV particles is not required and efficient gene expression can be achieved using either crude AdV lysates or HEK 293 cells infected with AdV. The advantages of the simplified procedure are greatly reduced preparation time and reduced requirements for equipment and expertise. JF - Neuroscience letters AU - Chen, Huanmian AU - Honse, Yumiko AU - Ikeda, Stephen R AD - Laboratory of Molecular Physiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Park Bldg. Room 150, 12420 Parklawn Drive, MSC 8115, Bethesda, MD 20892-8815, USA. huanchen@mail.nih.gov Y1 - 2004/09/23/ PY - 2004 DA - 2004 Sep 23 SP - 221 EP - 225 VL - 368 IS - 2 SN - 0304-3940, 0304-3940 KW - GABA Agonists KW - 0 KW - Pertussis Toxin KW - EC 2.4.2.31 KW - GTP-Binding Protein alpha Subunits, Gq-G11 KW - EC 3.6.5.1 KW - Baclofen KW - H789N3FKE8 KW - Index Medicus KW - Animals KW - Drug Interactions KW - Excitatory Postsynaptic Potentials -- genetics KW - Gene Transfer Techniques KW - Humans KW - Pertussis Toxin -- pharmacology KW - GTP-Binding Protein alpha Subunits, Gq-G11 -- pharmacology KW - Rats KW - Animals, Newborn KW - Rats, Sprague-Dawley KW - Patch-Clamp Techniques KW - Membrane Potentials -- genetics KW - Excitatory Postsynaptic Potentials -- drug effects KW - GABA Agonists -- pharmacology KW - Cells, Cultured KW - Genetic Vectors KW - Embryo, Mammalian KW - Baclofen -- pharmacology KW - Adenoviridae -- metabolism KW - Neurons -- metabolism KW - Hippocampus -- cytology KW - Neurons -- virology KW - Hippocampus -- virology KW - Gene Expression -- physiology KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66851459?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Alternative+modalities+of+adenovirus-mediated+gene+expression+in+hippocampal+neurons+cultured+on+microisland+substrate.&rft.au=Chen%2C+Huanmian%3BHonse%2C+Yumiko%3BIkeda%2C+Stephen+R&rft.aulast=Chen&rft.aufirst=Huanmian&rft.date=2004-09-23&rft.volume=368&rft.issue=2&rft.spage=221&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 - 2004-11-29 N1 - Date created - 2004-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CPAPER T1 - Juxtaposition of veillonellae and streptococci in undisturbed human dental plaque AN - 39862100; 3882018 AU - Palmer, R J AU - Kolenbrander, P E Y1 - 2004/09/21/ PY - 2004 DA - 2004 Sep 21 KW - CPI, Conference Papers Index KW - U 2000:Biology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/39862100?accountid=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=Juxtaposition+of+veillonellae+and+streptococci+in+undisturbed+human+dental+plaque&rft.au=Palmer%2C+R+J%3BKolenbrander%2C+P+E&rft.aulast=Palmer&rft.aufirst=R&rft.date=2004-09-21&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 International, 17 Rue du Cendrier, P.O. Box 1726, CH-1211, Geneva 1, Switzerland; email: isme@kenes.com; URL: www.kenes.com N1 - Last updated - 2010-05-03 ER - TY - JOUR T1 - Disulfiram is a potent modulator of multidrug transporter Cdr1p of Candida albicans. AN - 66806737; 15325261 AB - To find novel drugs for effective antifungal therapy in candidiasis, we examined disulfiram, a drug used for the treatment of alcoholism, for its role as a potential modulator of Candida multidrug transporter Cdr1p. We show that disulfiram inhibits the oligomycin-sensitive ATPase activity of Cdr1p and 2.5mM dithiothreitol reverses this inhibition. Disulfiram inhibited the binding of photoaffinity analogs of both ATP ([alpha-(32)P]8-azidoATP; IC(50)=0.76 microM) and drug-substrates ([(3)H]azidopine and [(125)I]iodoarylazidoprazosin; IC(50) approximately 12 microM) to Cdr1p in a concentration-dependent manner, suggesting that it can interact with both ATP and substrate-binding site(s) of Cdr1p. Furthermore, a non-toxic concentration of disulfiram (1 microM) increased the sensitivity of Cdr1p expressing Saccharomyces cerevisiae cells to antifungal agents (fluconazole, miconazole, nystatin, and cycloheximide). Collectively these results demonstrate that disulfiram reverses Cdr1p-mediated drug resistance by interaction with both ATP and substrate-binding sites of the transporter and may be useful for antifungal therapy. JF - Biochemical and biophysical research communications AU - Shukla, Suneet AU - Sauna, Zuben E AU - Prasad, Rajendra AU - Ambudkar, Suresh V AD - Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4256, USA. Y1 - 2004/09/17/ PY - 2004 DA - 2004 Sep 17 SP - 520 EP - 525 VL - 322 IS - 2 SN - 0006-291X, 0006-291X KW - Azides KW - 0 KW - CDR1 protein, Candida albicans KW - Enzyme Inhibitors KW - Fungal Proteins KW - Membrane Transport Proteins KW - Phosphorus Radioisotopes KW - 8-azidoadenosine 5'-triphosphate KW - 53696-59-6 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Disulfiram KW - TR3MLJ1UAI KW - Index Medicus KW - Azides -- metabolism KW - Adenosine Triphosphate -- analogs & derivatives KW - Adenosine Triphosphate -- metabolism KW - Genes, Reporter KW - Phosphorus Radioisotopes -- metabolism KW - Saccharomyces cerevisiae KW - Cloning, Molecular KW - Candida albicans -- drug effects KW - Candidiasis -- drug therapy KW - Fungal Proteins -- metabolism KW - Fungal Proteins -- drug effects KW - Membrane Transport Proteins -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Disulfiram -- pharmacology KW - Membrane Transport Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66806737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Disulfiram+is+a+potent+modulator+of+multidrug+transporter+Cdr1p+of+Candida+albicans.&rft.au=Shukla%2C+Suneet%3BSauna%2C+Zuben+E%3BPrasad%2C+Rajendra%3BAmbudkar%2C+Suresh+V&rft.aulast=Shukla&rft.aufirst=Suneet&rft.date=2004-09-17&rft.volume=322&rft.issue=2&rft.spage=520&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 - 2004-10-27 N1 - Date created - 2004-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extracellular Mycobacterial DNA-binding Protein 1 Participates in Mycobacterium-Lung Epithelial Cell Interaction through Hyaluronic Acid AN - 17762360; 6030630 AB - Mycobacterium tuberculosis infects not only host macrophages but also nonprofessional phagocytes, such as alveolar epithelial cells. Glycosaminoglycans (GAGs) are considered as the component of mycobacterial adherence to epithelial cells. Here we show that extracellularly occurring mycobacterial DNA-binding protein 1 (MDP1) promotes mycobacterial infection to A549 human lung epithelial cells through hyaluronic acid (HA). Both surface plasmon resonance analysis and enzyme-linked immunosorbent assay revealed that MDP1 bound to HA, heparin, and chondroitin sulfate. Utilizing synthetic peptides, we next defined heparin-binding site of 20 amino acids from 31 to 50 of MDP1, which is responsible for the specific DNA-binding site of MDP1. MDP1 bound to A549 cells, and exogenous DNA and HA interfered with the interaction. The binding was also abolished by treatment of A549 cells with hyaluronidase, suggesting that HA participates in the MDP1-A549 cell interaction. Adherence of bacillus Calmette-Guerin (BCG) and M. tuberculosis to A549 cells was inhibited by addition of HA, DNA, and anti-MDP1 antibody, showing that MDP1 participates in the interaction between mycobacteria-alveolar epithelial cells. Simultaneous treatment of intratracheal BCG-infected mice with HA reduced the growth of BCG in vivo. Taken together, theses results suggest that HA participates in Mycobacterium-lung epithelium interaction and has potential for therapeutic and prophylactic interventions in mycobacterial infection. JF - Journal of Biological Chemistry AU - Aoki, Keiko AU - Matsumoto, Sohkichi AU - Hirayama, Yukio AU - Wada, Takayuki AU - Ozeki, Yuriko AU - Niki, Makoto AU - Domenech, Pilar AU - Umemori, Kiyoko AU - Yamamoto, Saburo AU - Mineda, Amao AU - Matsumoto, Makoto AU - Kobayashi, Kazuo AD - Department of Host Defense, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan, the Osaka City Institute of Public Health and Environmental Sciences, Osaka 545-8585, Japan, Osaka International College for Woman, 6-21-57 Tohdacho, Moriguchi, Osaka 570- 8555, Japan, the Tuberculosis Research Section, Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, Maryland Y1 - 2004/09/17/ PY - 2004 DA - 2004 Sep 17 SP - 39798 EP - 39806 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 - 279 IS - 38 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Macrophages KW - Hyaluronic acid KW - Epithelial cells KW - synthetic peptides KW - Chondroitin sulfate KW - Hyaluronidase KW - DNA-binding protein KW - Infection KW - Alveoli KW - Antibodies KW - surface plasmon resonance KW - Glycosaminoglycans KW - BCG KW - Tuberculosis KW - Epithelium KW - Cell interactions KW - Trachea KW - Heparin KW - Mycobacterium tuberculosis KW - N 14025:RNA/DNA role in infection & immune response KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17762360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Extracellular+Mycobacterial+DNA-binding+Protein+1+Participates+in+Mycobacterium-Lung+Epithelial+Cell+Interaction+through+Hyaluronic+Acid&rft.au=Aoki%2C+Keiko%3BMatsumoto%2C+Sohkichi%3BHirayama%2C+Yukio%3BWada%2C+Takayuki%3BOzeki%2C+Yuriko%3BNiki%2C+Makoto%3BDomenech%2C+Pilar%3BUmemori%2C+Kiyoko%3BYamamoto%2C+Saburo%3BMineda%2C+Amao%3BMatsumoto%2C+Makoto%3BKobayashi%2C+Kazuo&rft.aulast=Aoki&rft.aufirst=Keiko&rft.date=2004-09-17&rft.volume=279&rft.issue=38&rft.spage=39798&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Macrophages; Epithelial cells; Hyaluronic acid; Hyaluronidase; Chondroitin sulfate; synthetic peptides; DNA-binding protein; Infection; Alveoli; Antibodies; Glycosaminoglycans; surface plasmon resonance; BCG; Epithelium; Tuberculosis; Cell interactions; Heparin; Trachea; Mycobacterium tuberculosis ER - TY - JOUR T1 - The Transcriptional Responses of Mycobacterium tuberculosis to Inhibitors of Metabolism: Novel Insights into Drug Mechanisms of Action AN - 17760239; 6030994 AB - The differential transcriptional response of Mycobacterium tuberculosis to drugs and growth-inhibitory conditions was monitored to generate a data set of 430 microarray profiles. Unbiased grouping of these profiles independently clustered agents of known mechanism of action accurately and was successful at predicting the mechanism of action of several unknown agents. These predictions were validated biochemically for two agents of previously uncategorized mechanism, pyridoacridones and phenothiazines. Analysis of this data set further revealed 150 underlying clusters of coordinately regulated genes offering the first glimpse at the full metabolic potential of this organism. A signature subset of these gene clusters was sufficient to classify all known agents as to mechanism of action. Transcriptional profiling of both crude and purified natural products can provide critical information on both mechanism and detoxification prior to purification that can be used to guide the drug discovery process. Thus, the transcriptional profile generated by a crude marine natural product recapitulated the mechanistic prediction from the pure active component. The underlying gene clusters further provide fundamental insights into the metabolic response of bacteria to drug-induced stress and provide a rational basis for the selection of critical metabolic targets for screening for new agents with improved activity against this important human pathogen. JF - Journal of Biological Chemistry AU - Boshoff, Helena IM AU - Myers, Timothy G AU - Copp, Brent R AU - Mcneil, Michael R AU - Wilson, Michael A AU - Barry, Clifton E AD - Tuberculosis Research Section, NIAID, National Institutes of Health, Rockville, Maryland Y1 - 2004/09/17/ PY - 2004 DA - 2004 Sep 17 SP - 40174 EP - 40184 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 - 279 IS - 38 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Detoxification KW - Data processing KW - phenothiazine KW - Stress KW - Transcription KW - natural products KW - Pathogens KW - DNA microarrays KW - Drug discovery KW - Purification KW - Drugs KW - Metabolism KW - Metabolic response KW - Mycobacterium tuberculosis KW - N 14941:Miscellaneous KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17760239?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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+Transcriptional+Responses+of+Mycobacterium+tuberculosis+to+Inhibitors+of+Metabolism%3A+Novel+Insights+into+Drug+Mechanisms+of+Action&rft.au=Boshoff%2C+Helena+IM%3BMyers%2C+Timothy+G%3BCopp%2C+Brent+R%3BMcneil%2C+Michael+R%3BWilson%2C+Michael+A%3BBarry%2C+Clifton+E&rft.aulast=Boshoff&rft.aufirst=Helena&rft.date=2004-09-17&rft.volume=279&rft.issue=38&rft.spage=40174&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Transcription; natural products; Data processing; Drug discovery; DNA microarrays; Detoxification; phenothiazine; Metabolic response; Drugs; Pathogens; Purification; Metabolism; Stress ER - TY - JOUR T1 - Rimonabant, a CB1 antagonist, blocks nicotine-conditioned place preferences. AN - 66977384; 15486497 AB - The effects of Rimonabant (SR141716), an antagonist at cannabinoid CB1 receptors, were evaluated in animal models for subjective and rewarding effects of nicotine. Acute administration of 1 or 3 mg/kg SR141716 blocked expression of nicotine-induced conditioned place preferences. SR141716 (0.3-3 mg/kg) was also studied in rats trained to discriminate nicotine from saline under a fixed-ratio schedule of food delivery. In contrast to nicotine replacement therapy and bupropion, SR141716 did not have nicotine-like discriminative effects and did not alter the dose-response curve for nicotine discrimination. These findings support the proposed use of SR141716 for smoking cessation and indicate that it would selectively reduce the influence of environmental stimuli that contribute to persistent smoking behavior, without affecting subjective responses to nicotine. JF - Neuroreport AU - Le Foll, Bernard AU - Goldberg, Steven R AD - Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. blefoll@intra.nida.nih.gov Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 2139 EP - 2143 VL - 15 IS - 13 SN - 0959-4965, 0959-4965 KW - Nicotinic Agonists KW - 0 KW - Piperidines KW - Pyrazoles KW - Receptor, Cannabinoid, CB1 KW - Nicotine KW - 6M3C89ZY6R KW - rimonabant KW - RML78EN3XE KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Male KW - Behavior, Animal KW - Piperidines -- pharmacology KW - Conditioning, Operant -- drug effects KW - Pyrazoles -- pharmacology KW - Receptor, Cannabinoid, CB1 -- antagonists & inhibitors KW - Nicotine -- pharmacology KW - Reinforcement (Psychology) KW - Nicotinic Agonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66977384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=Rimonabant%2C+a+CB1+antagonist%2C+blocks+nicotine-conditioned+place+preferences.&rft.au=Le+Foll%2C+Bernard%3BGoldberg%2C+Steven+R&rft.aulast=Le+Foll&rft.aufirst=Bernard&rft.date=2004-09-15&rft.volume=15&rft.issue=13&rft.spage=2139&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-01-13 N1 - Date created - 2004-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bevacizumab for patients with metastatic renal cancer: an update. AN - 66913240; 15448032 AB - Most clear cell renal cell cancer (RCC) is caused by biallelic loss of the von Hippel-Lindau gene. One consequence of this loss is up-regulation of vascular endothelial growth factor via a pathway involving accumulation of hypoxia inducible factor. Vascular endothelial growth factor, a potent angiogenic factor, is secreted by many human cancers, but clear cell RCC as a group produces particularly high levels and has a highly vascular histologic appearance. In a randomized, placebo-controlled, double-blind trial, we tested the use of a neutralizing antibody to vascular endothelial growth factor, bevacizumab, in patients with metastatic RCC. At 3 or 10 mg/kg every 2 weeks, toxic effects were minimal, with hypertension and proteinuria the most substantial events. There were four partial responses (10% response rate) and a highly substantial prolongation of time to tumor progression in patients who received the higher dose of bevacizumab. With a crossover design and very sensitive criteria for disease progression, no difference in survival was shown. Four patients have been undergoing long-term bevacizumab therapy without tumor progression for 3 to 5 years. Three have substantial proteinuria but retain normal renal function. A small pilot trial combining bevacizumab and thalidomide showed no unexpected toxic effects. Future trials should consider combination therapies and strategies in which patients are treated through initial disease progression with antiangiogenic agents such as bevacizumab. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Yang, James C AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. james_yang@nih.gov Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 6367S EP - 70S VL - 10 IS - 18 Pt 2 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Monoclonal, Humanized KW - Antineoplastic Agents KW - Tumor Suppressor Proteins KW - Bevacizumab KW - 2S9ZZM9Q9V 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 - Randomized Controlled Trials as Topic KW - Neoplasm Staging KW - Humans KW - Ubiquitin-Protein Ligases -- genetics KW - von Hippel-Lindau Disease -- genetics KW - Tumor Suppressor Proteins -- genetics KW - Neoplasm Metastasis KW - Kidney Neoplasms -- genetics KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- pathology KW - Kidney Neoplasms -- drug therapy KW - Carcinoma, Renal Cell -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Carcinoma, Renal Cell -- immunology KW - Carcinoma, Renal Cell -- genetics KW - Kidney Neoplasms -- immunology KW - Antibodies, Monoclonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66913240?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Bevacizumab+for+patients+with+metastatic+renal+cancer%3A+an+update.&rft.au=Yang%2C+James+C&rft.aulast=Yang&rft.aufirst=James&rft.date=2004-09-15&rft.volume=10&rft.issue=18+Pt+2&rft.spage=6367S&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 - 2004-12-01 N1 - Date created - 2004-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transforming growth factor-beta pathway serves as a primary tumor suppressor in CD8+ T cell tumorigenesis. AN - 66885017; 15374963 AB - Tumorigenesis in rodents, as well as in humans, has been shown to be a multistep process, with each step reflecting an altered gene product or gene regulatory process leading to autonomy of cell growth. Initial genetic mutations are often associated with dysfunctional growth regulation, as is demonstrated in several transgenic mouse models. These changes are often followed by alterations in tumor suppressor gene function, allowing unchecked cell cycle progression and, by genomic instability, additional genetic mutations responsible for tumor metastasis. Here we show that reduced transforming growth factor-beta signaling in T lymphocytes leads to a rapid expansion of a CD8+ memory T-cell population and a subsequent transformation to leukemia/lymphoma as shown by multiple criteria, including peripheral blood cell counts histology, T-cell receptor monoclonality, and host transferability. Furthermore, spectral karyotype analysis of the tumors shows that the tumors have various chromosomal aberrations. These results suggest that reduced transforming growth factor-beta signaling acts as a primary carcinogenic event, allowing uncontrolled proliferation with consequent accumulation of genetic defects and leukemic transformation. JF - Cancer research AU - Lucas, Philip J AU - McNeil, Nicole AU - Hilgenfeld, Eva AU - Choudhury, Baishakhi AU - Kim, Seong-Jin AU - Eckhaus, Michael A AU - Ried, Thomas AU - Gress, Ronald E AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 6524 EP - 6529 VL - 64 IS - 18 SN - 0008-5472, 0008-5472 KW - Receptors, Antigen, T-Cell KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Animals KW - Cell Transformation, Neoplastic -- pathology KW - Receptors, Transforming Growth Factor beta -- immunology KW - Mice, Inbred C57BL KW - Immunologic Memory KW - Chromosome Aberrations KW - Receptors, Antigen, T-Cell -- immunology KW - Mice KW - Mice, Transgenic KW - Cell Transformation, Neoplastic -- immunology KW - Signal Transduction KW - Lymphoproliferative Disorders -- genetics KW - Leukemia, T-Cell -- genetics KW - CD8-Positive T-Lymphocytes -- pathology KW - CD8-Positive T-Lymphocytes -- immunology KW - Lymphoproliferative Disorders -- pathology KW - Lymphoproliferative Disorders -- immunology KW - Transforming Growth Factor beta -- immunology KW - Leukemia, T-Cell -- immunology KW - Leukemia, T-Cell -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66885017?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Transforming+growth+factor-beta+pathway+serves+as+a+primary+tumor+suppressor+in+CD8%2B+T+cell+tumorigenesis.&rft.au=Lucas%2C+Philip+J%3BMcNeil%2C+Nicole%3BHilgenfeld%2C+Eva%3BChoudhury%2C+Baishakhi%3BKim%2C+Seong-Jin%3BEckhaus%2C+Michael+A%3BRied%2C+Thomas%3BGress%2C+Ronald+E&rft.aulast=Lucas&rft.aufirst=Philip&rft.date=2004-09-15&rft.volume=64&rft.issue=18&rft.spage=6524&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 - 2004-11-04 N1 - Date created - 2004-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A functional polymorphism in RGS6 modulates the risk of bladder cancer. AN - 66884847; 15375002 AB - RGS proteins negatively regulate heterotrimeric G protein signaling. Recent reports have shown that RGS proteins modulate neuronal, cardiovascular, and lymphocytic activity, yet their role in carcinogenesis has not been explored. In an epidemiologic study of 477 bladder cancer patients and 446 matched controls, three noncoding single-nucleotide polymorphisms (SNPs) in RGS2 and RGS6 were each associated with a statistically significant reduction in bladder cancer risk. The risk of bladder cancer was reduced by 74% in those individuals with the variant genotype at all three SNPs (odds ratio, 0.26; 95% confidence interval, 0.09-0.71). When the SNPs were analyzed separately, the RGS6-rs2074647 (C-->T) polymorphism conferred the greatest overall reduction in risk of bladder cancer (odds ratio, 0.66; 95% confidence interval, 0.46-0.95). These reductions in risk were more pronounced in ever smokers, suggesting a gene-environment interaction. In transfection assays, the RGS6-rs2074647 (C-->T) polymorphism increased the activity of a luciferase-RGS fusion protein by 2.9-fold, suggesting that this SNP is functionally significant. Finally, we demonstrate that RGS2 transcripts and several splice variants of RGS6 are expressed in bladder cancer cells. These data provide the first evidence that RGS proteins may be important modulators of cancer risk and validate RGS6 as a target for further study. JF - Cancer research AU - Berman, David M AU - Wang, Yunfei AU - Liu, Zhengyu AU - Dong, Qiong AU - Burke, Lorri-Anne AU - Liotta, Lance A AU - Fisher, Rory AU - Wu, Xifeng AD - Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA. bermand@mail.nih.gov Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 6820 EP - 6826 VL - 64 IS - 18 SN - 0008-5472, 0008-5472 KW - RGS Proteins KW - 0 KW - RGS2 protein, human KW - RGS6 protein, human KW - Index Medicus KW - Smoking KW - Polymorphism, Single Nucleotide KW - Humans KW - Case-Control Studies KW - Middle Aged KW - Genetic Predisposition to Disease KW - Male KW - Female KW - RGS Proteins -- genetics KW - Urinary Bladder Neoplasms -- genetics KW - Urinary Bladder Neoplasms -- metabolism KW - RGS Proteins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66884847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+functional+polymorphism+in+RGS6+modulates+the+risk+of+bladder+cancer.&rft.au=Berman%2C+David+M%3BWang%2C+Yunfei%3BLiu%2C+Zhengyu%3BDong%2C+Qiong%3BBurke%2C+Lorri-Anne%3BLiotta%2C+Lance+A%3BFisher%2C+Rory%3BWu%2C+Xifeng&rft.aulast=Berman&rft.aufirst=David&rft.date=2004-09-15&rft.volume=64&rft.issue=18&rft.spage=6820&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 - 2004-11-04 N1 - Date created - 2004-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study. AN - 66875694; 15367568 AB - Men treated for clinically localized prostate cancer with either radical prostatectomy or external beam radiotherapy usually survive many years with the side effects of these treatments. We present treatment-specific quality-of-life outcomes for prostate cancer patients 5 years after initial diagnosis. The cohort consisted of men aged 55-74 years who were newly diagnosed with clinically localized prostate cancer in 1994-1995 and were treated with radical prostatectomy (n = 901) or external beam radiotherapy (n = 286). We used clinical and quality-of-life data previously collected at the time of diagnosis (i.e., baseline) and at the 2-year follow-up and data newly collected at 5 years after diagnosis to compare urinary, bowel, and sexual function and to examine temporal changes in those functions. Odds ratios (ORs) and adjusted percentages were calculated by logistic regression. All statistical tests were two-sided. At 5 years after diagnosis, overall sexual function declined in both groups to approximately the same level. However, at 5 years after diagnosis, erectile dysfunction was more prevalent in the radical prostatectomy group than in the external beam radiotherapy group (79.3% versus 63.5%; OR = 2.5, 95% confidence interval [CI] = 1.6 to 3.8). Approximately 14%-16% of radical prostatectomy and 4% of external beam radiotherapy patients were incontinent at 5 years (OR = 4.4, 95% CI = 2.2 to 8.6). Bowel urgency and painful hemorrhoids were more common in the external beam radiotherapy group than in the radical prostatectomy group. All of these differences remained statistically significant after adjustment for confounders and for differences between treatment groups in some baseline characteristics. At 5 years after diagnosis, men treated with radical prostatectomy for localized prostate cancer continue to experience worse urinary incontinence than men treated with external beam radiotherapy. However, the two treatment groups were more similar to each other with respect to overall sexual function, mostly because of a continuing decline in erectile function among the external beam radiotherapy patients between years 2 and 5. JF - Journal of the National Cancer Institute AU - Potosky, Arnold L AU - Davis, William W AU - Hoffman, Richard M AU - Stanford, Janet L AU - Stephenson, Robert A AU - Penson, David F AU - Harlan, Linda C AD - Division of Cancer Control and Population Sciences, National Cancer Institute, EPN Rm. 4005, 6130 Executive Blvd., MSC 7344, Bethesda, MD 20892-7344, USA. potosky@nih.gov Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 1358 EP - 1367 VL - 96 IS - 18 KW - Index Medicus KW - Socioeconomic Factors KW - Prospective Studies KW - Logistic Models KW - Humans KW - Surveys and Questionnaires KW - Aged KW - Middle Aged KW - Selection Bias KW - Research Design KW - Male KW - Urinary Incontinence -- etiology KW - Prostatectomy -- adverse effects KW - Prostatic Neoplasms -- surgery KW - Quality of Life KW - Fecal Incontinence -- etiology KW - Erectile Dysfunction -- etiology KW - Radiotherapy, Adjuvant -- adverse effects KW - Prostatic Neoplasms -- therapy KW - Prostatic Neoplasms -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66875694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Five-year+outcomes+after+prostatectomy+or+radiotherapy+for+prostate+cancer%3A+the+prostate+cancer+outcomes+study.&rft.au=Potosky%2C+Arnold+L%3BDavis%2C+William+W%3BHoffman%2C+Richard+M%3BStanford%2C+Janet+L%3BStephenson%2C+Robert+A%3BPenson%2C+David+F%3BHarlan%2C+Linda+C&rft.aulast=Potosky&rft.aufirst=Arnold&rft.date=2004-09-15&rft.volume=96&rft.issue=18&rft.spage=1358&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 - 2004-09-29 N1 - Date created - 2004-09-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 2004 Sep 15;96(18):1348-9 [15367562] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - LFA-1 contributes an early signal for NK cell cytotoxicity. AN - 66861472; 15356110 AB - Cytotoxicity of human NK cells is activated by receptors that bind ligands on target cells, but the relative contribution of the many different activating and inhibitory NK cell receptors is difficult to assess. In this study, we describe an experimental system that circumvents some of the difficulties. Adhesion through beta2 integrin LFA-1 is a common requirement of CTLs and NK cells for efficient lysis of target cells. However, the contribution of LFA-1 to activation signals for NK cell cytotoxicity, besides its role in adhesion, is unclear. The role of LFA-1 was evaluated by exposing NK cells to human ICAM-1 that was either expressed on a Drosophila insect cell line, or directly coupled to beads. Expression of ICAM-1 on insect cells was sufficient to induce lysis by NK cells through LFA-1. Coexpression of peptide-loaded HLA-C with ICAM-1 on insect cells blocked the LFA-1-dependent cytotoxicity of NK cells that expressed HLA-C-specific inhibitory receptors. Polarization of cytotoxic granules in NK cells toward ICAM-1- and ICAM-2-coated beads showed that engagement of LFA-1 alone is sufficient to initiate activation signals in NK cells. Thus, in contrast to T cells, in which even adhesion through LFA-1 is dependent on signals from other receptors, NK cells receive early activation signals directly through LFA-1. Copyright 2004 The American Association of Immunologists, Inc. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Barber, Domingo F AU - Faure, Mathias AU - Long, Eric O AD - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 3653 EP - 3659 VL - 173 IS - 6 SN - 0022-1767, 0022-1767 KW - Lymphocyte Function-Associated Antigen-1 KW - 0 KW - Membrane Glycoproteins KW - Pore Forming Cytotoxic Proteins KW - Protein Isoforms KW - Receptors, Immunologic KW - Receptors, KIR KW - Perforin KW - 126465-35-8 KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - Abridged Index Medicus KW - Index Medicus KW - Clone Cells KW - Animals KW - Cytotoxicity Tests, Immunologic -- methods KW - Receptors, Immunologic -- physiology KW - Humans KW - Intercellular Adhesion Molecule-1 -- biosynthesis KW - Protein Isoforms -- physiology KW - Intercellular Adhesion Molecule-1 -- genetics KW - Protein Isoforms -- toxicity KW - Cell Death -- immunology KW - Cytoplasmic Granules -- metabolism KW - Drosophila -- cytology KW - Intercellular Adhesion Molecule-1 -- physiology KW - Transfection KW - Lymphocyte Activation -- immunology KW - Cell Adhesion -- immunology KW - Drosophila -- genetics KW - Cell Line KW - Membrane Glycoproteins -- metabolism KW - Lymphocyte Function-Associated Antigen-1 -- metabolism KW - Signal Transduction -- immunology KW - Cytotoxicity, Immunologic -- genetics KW - Killer Cells, Natural -- cytology KW - Killer Cells, Natural -- metabolism KW - Lymphocyte Function-Associated Antigen-1 -- physiology KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66861472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=LFA-1+contributes+an+early+signal+for+NK+cell+cytotoxicity.&rft.au=Barber%2C+Domingo+F%3BFaure%2C+Mathias%3BLong%2C+Eric+O&rft.aulast=Barber&rft.aufirst=Domingo&rft.date=2004-09-15&rft.volume=173&rft.issue=6&rft.spage=3653&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 - 2004-10-19 N1 - Date created - 2004-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of a dipeptide motif regulating IFN-gamma receptor 2 plasma membrane accumulation and IFN-gamma responsiveness. AN - 66858252; 15356148 AB - The IFN-gammaR complex is composed of two IFN-gammaR1 and two IFN-gammaR2 polypeptide chains. Although IFN-gammaR1 is constitutively expressed on all nucleated cells, IFN-gammaR2 membrane display is selective and tightly regulated. We created a series of fluorescent-tagged IFN-gammaR2 expression constructs to follow the molecule's cell surface expression and intracellular distribution. Truncation of the receptor immediately upstream of Leu-Ile 255-256 (254X) created a receptor devoid of signaling that overaccumulated on the cell surface. In addition, this truncated receptor inhibited wild-type IFN-gammaR2 activity and therefore exerted a dominant negative effect. In-frame deletion (255Delta2) or alanine substitution (LI255-256AA) of these amino acids created mutants that overaccumulated on the plasma membrane, but had enhanced function. Single amino acid substitutions (L255A or I256A) had a more modest effect. In-frame deletions upstream (253Delta2), but not downstream (257Delta2), of Leu-Ile 255-256 also led to overaccumulation. A truncation within the IFN-gammaR2 Jak2 binding site (270X) led to a mutant devoid of function that did not overaccumulate and did not affect wild-type IFN-gammaR2 signaling. We have created a series of novel mutants of IFN-gammaR2 that have facilitated the identification of intracellular domains that control IFN-gammaR2 accumulation and IFN-gamma responsiveness. In contrast to IFN-gammaR1, not only dominant negative, but also dominant gain-of-function, mutations were created through manipulation of IFN-gammaR2 Leu-Ile 255-256. These IFN-gammaR2 mutants will allow fine dissection of the role of IFN-gamma signaling in immunity. Copyright 2004 The American Association of Immunologists, Inc. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Rosenzweig, Sergio D AU - Schwartz, Owen M AU - Brown, Margaret R AU - Leto, Thomas L AU - Holland, Steven M AD - Laboratory of Host Defenses, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 3991 EP - 3999 VL - 173 IS - 6 SN - 0022-1767, 0022-1767 KW - Dipeptides KW - 0 KW - IFNGR2 protein, human KW - Luminescent Proteins KW - Protein Sorting Signals KW - Receptors, Interferon KW - Recombinant Fusion Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Interferon-gamma KW - 82115-62-6 KW - Mannosidases KW - EC 3.2.1.- KW - endo-1,4-beta-D-mannanase KW - EC 3.2.1.78 KW - Abridged Index Medicus KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Amino Acid Motifs -- immunology KW - Protein Sorting Signals -- genetics KW - Amino Acid Motifs -- genetics KW - Humans KW - Intracellular Fluid -- metabolism KW - Recombinant Fusion Proteins -- physiology KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Cell Aggregation -- genetics KW - Down-Regulation -- genetics KW - Transfection KW - Genetic Vectors KW - Mannosidases -- pharmacology KW - Intracellular Fluid -- chemistry KW - Signal Transduction -- genetics KW - Intracellular Fluid -- immunology KW - Signal Transduction -- immunology KW - Mannosidases -- metabolism KW - Cell Aggregation -- immunology KW - Cell Line, Transformed KW - Luminescent Proteins -- genetics KW - Cell Line KW - Receptors, Interferon -- physiology KW - Dipeptides -- chemistry KW - Interferon-gamma -- antagonists & inhibitors KW - Cell Membrane -- immunology KW - Dipeptides -- physiology KW - Cell Membrane -- genetics KW - Receptors, Interferon -- genetics KW - Interferon-gamma -- metabolism KW - Interferon-gamma -- physiology KW - Cell Membrane -- metabolism KW - Receptors, Interferon -- metabolism KW - Dipeptides -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66858252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc: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=Characterization+of+a+dipeptide+motif+regulating+IFN-gamma+receptor+2+plasma+membrane+accumulation+and+IFN-gamma+responsiveness.&rft.au=Rosenzweig%2C+Sergio+D%3BSchwartz%2C+Owen+M%3BBrown%2C+Margaret+R%3BLeto%2C+Thomas+L%3BHolland%2C+Steven+M&rft.aulast=Rosenzweig&rft.aufirst=Sergio&rft.date=2004-09-15&rft.volume=173&rft.issue=6&rft.spage=3991&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 - 2004-10-19 N1 - Date created - 2004-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 3,4-methylenedioxymethamphetamine (MDMA) administration to rats decreases brain tissue serotonin but not serotonin transporter protein and glial fibrillary acidic protein. AN - 66731479; 15266556 AB - Previous experiments conducted in this laboratory showed that administration of high-dose D-fenfluramine (D-FEN) and p-chloroamphetamine (PCA) decreased 5-HT transporter (SERT) binding and tissue 5-HT by 30-60% in caudate and whole brain tissue 2 days and 2 weeks after drug administration. However, protein expression as determined by Western blot analysis did not change in either tissue or time point, except for a 30% decrease in the caudate 2 days after PCA administration. In the present study, we studied the effect of MDMA and 5,7-dihydroxytryptamine (5,7-DHT) on tissue 5-HT levels and the protein expression level of SERT and glial fibrillary acidic protein (GFAP), a validated neurotoxicity marker. MDMA administration decreases SERT expression. Two weeks after MDMA administration (7.5 mg/kg i.p., q 2 h x 3 doses) or 2 weeks after i.c.v. administration of 5,7,-DHT (150 microg/rat), male Sprague-Dawley rats were sacrificed and the caudate, cortex, and hippocampal tissue collected. Western blots for SERT and GFAP were generated using published methods. Tissue 5-HT levels were determined by HPLC coupled to electrochemical detection. MDMA treatment decreased tissue 5-HT in cortex, hippocampus, and caudate by about 50%. However, MDMA treatment had no significant effect on expression level of SERT and GFAP in any brain region. In contrast, 5,7-DHT reduced tissue 5-HT by more than 90%, decreased SERT protein expression by 20-35%, and increased GFAP by 30-39%. These data suggest the MDMA treatment regimen used here does not cause degeneration of 5-HT nerve terminals. Viewed collectively with our previous results and other published data, these data indicate that MDMA-induced persistent 5-HT depletion may occur in the absence of axotomy. JF - Synapse (New York, N.Y.) AU - Wang, Xiaoying AU - Baumann, Michael H AU - Xu, Heng AU - Rothman, Richard B AD - Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 240 EP - 248 VL - 53 IS - 4 SN - 0887-4476, 0887-4476 KW - Carrier Proteins KW - 0 KW - Glial Fibrillary Acidic Protein KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Neurotoxins KW - Serotonin Plasma Membrane Transport Proteins KW - Slc6a4 protein, rat KW - 3,4-Dihydroxyphenylacetic Acid KW - 102-32-9 KW - 5,7-Dihydroxytryptamine KW - 31363-74-3 KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - N-Methyl-3,4-methylenedioxyamphetamine KW - KE1SEN21RM KW - Norepinephrine KW - X4W3ENH1CV KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Animals KW - Neurons -- metabolism KW - Astrocytes -- drug effects KW - Hydroxyindoleacetic Acid -- metabolism KW - Neurons -- drug effects KW - Neurotoxins -- pharmacology KW - Homovanillic Acid -- metabolism KW - Up-Regulation -- physiology KW - Rats KW - Rats, Sprague-Dawley KW - Down-Regulation -- physiology KW - 3,4-Dihydroxyphenylacetic Acid -- metabolism KW - Norepinephrine -- metabolism KW - Up-Regulation -- drug effects KW - 5,7-Dihydroxytryptamine -- pharmacology KW - Down-Regulation -- drug effects KW - Male KW - Astrocytes -- metabolism KW - Nerve Tissue Proteins -- drug effects KW - Membrane Glycoproteins -- drug effects KW - Carrier Proteins -- metabolism KW - Brain -- drug effects KW - Brain Chemistry -- drug effects KW - Glial Fibrillary Acidic Protein -- metabolism KW - Brain -- metabolism KW - N-Methyl-3,4-methylenedioxyamphetamine -- pharmacology KW - Carrier Proteins -- drug effects KW - Glial Fibrillary Acidic Protein -- drug effects KW - Nerve Tissue Proteins -- metabolism KW - Serotonin -- metabolism KW - Brain Chemistry -- physiology KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66731479?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=3%2C4-methylenedioxymethamphetamine+%28MDMA%29+administration+to+rats+decreases+brain+tissue+serotonin+but+not+serotonin+transporter+protein+and+glial+fibrillary+acidic+protein.&rft.au=Wang%2C+Xiaoying%3BBaumann%2C+Michael+H%3BXu%2C+Heng%3BRothman%2C+Richard+B&rft.aulast=Wang&rft.aufirst=Xiaoying&rft.date=2004-09-15&rft.volume=53&rft.issue=4&rft.spage=240&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 - 2004-11-10 N1 - Date created - 2004-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thioredoxin Reductase as a Potential Molecular Target for Anticancer Agents That Induce Oxidative Stress AN - 20217733; 6030454 AB - Redox-sensitive signaling factors regulate multiple cellular processes, including proliferation, cell cycle, and prosurvival signaling cascades, suggesting their potential as molecular targets for anticancer agents. It is logical to set constraints that a molecular target should meet at least one of the following criteria: (1) inhibition of prosurvival signaling pathways; (2) inhibition of cell cycle progression; or (3) enhancement of the cytotoxic effects of anticancer agents. Therefore, we hypothesized that thioredoxin reductase 1 (TR), a component of several redox-regulated pathways, might represent a potential molecular target candidate in response to agents that induce oxidative stress. To address this issue, permanent cell lines overexpressing either the wild-type (pCXN2-myc-TR-wt) or a Cys-Ser mutant (pCXN2-myc-mTR) TR gene were used, as were parental HeLa cells treated with 1- methyl-1-propyl-2-imidazolyl disulfide (IV-2), a pharmacologic inhibitor of TR. Cells were exposed to the oxidative stressors, H sub(2)O sub(2) and ionizing radiation (IR), and analyzed for changes in signal transduction, cell cycle, and cytotoxicity. Analysis of HeLa cells overexpressing the pCXN2-myc-TR-wt gene showed increased basal activity of nuclear factor Kappa B (NF Kappa B) and activator protein (AP-1), whereas HeLa cells expressing a pCXN2-myc-mTR gene and HeLa cells treated with IV-2 were unable to induce NF Kappa B or AP-1 activity following H sub(2)O sub(2) or IR exposure. Fluorescence-activated cell sorting analysis showed a marked accumulation of pCXN2-myc-mTR cells in the late G sub(1) phase, whereas pCXN2-myc-TR-wt cells showed a decreased G sub(1) subpopulation. Chemical inhibition of TR with IV-2 also completely inhibited cellular proliferation at concentrations between 10 and 25 mu mol/L, resulting in a G sub(1) phase cell cycle arrest consistent with the results from cells expressing the pCXN2-myc-mTR gene. Following exposure to H sub(2)O sub(2) and IR, pCXN2-myc- mTR- and IV-2-treated cells were significantly more sensitive to oxidative stress-induced cytotoxicity as measured by clonogenic survival assays. Finally, IV-2-treated cells showed increased tumor cell death when treated with H sub(2)O sub(2) and IR. These results identify TR as a potential target to enhance the cytotoxic effects of agents that induce oxidative stress, including IR. JF - Cancer Research AU - Smart, Deedee K AU - Ortiz, Karen L AU - Mattson, David AU - Bradbury, CMatthew AU - Bisht, Kheem S AU - Sieck, Leah K AU - Brechbiel, Martin W AU - Gius, David AD - Molecular Radiation Oncology Section and Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, Radiation Oncology Sciences Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 6716 EP - 6724 PB - Maclean-Hunter Ltd. VL - 64 IS - 18 SN - 0008-5472, 0008-5472 KW - Biotechnology and Bioengineering Abstracts KW - Cell survival KW - Activator protein 1 KW - Cell cycle KW - Thioredoxin-disulfide reductase KW - Antitumor agents KW - Tumor cells KW - Cancer KW - Flow cytometry KW - Cytotoxicity KW - Oxidative stress KW - Hydrogen peroxide KW - Ionizing radiation KW - Transcription factors KW - G1 phase KW - thioredoxin reductase KW - Cell proliferation KW - Signal transduction KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20217733?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Thioredoxin+Reductase+as+a+Potential+Molecular+Target+for+Anticancer+Agents+That+Induce+Oxidative+Stress&rft.au=Smart%2C+Deedee+K%3BOrtiz%2C+Karen+L%3BMattson%2C+David%3BBradbury%2C+CMatthew%3BBisht%2C+Kheem+S%3BSieck%2C+Leah+K%3BBrechbiel%2C+Martin+W%3BGius%2C+David&rft.aulast=Smart&rft.aufirst=Deedee&rft.date=2004-09-15&rft.volume=64&rft.issue=18&rft.spage=6716&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 - 2009-09-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Cell survival; Cell cycle; Activator protein 1; Thioredoxin-disulfide reductase; Tumor cells; Antitumor agents; Cancer; Flow cytometry; Cytotoxicity; Hydrogen peroxide; Oxidative stress; Transcription factors; Ionizing radiation; G1 phase; thioredoxin reductase; Cell proliferation; Signal transduction ER - TY - JOUR T1 - Future Research Directions in Asthma An NHLBI Working Group Report AN - 199575912; 15215155 AB - Over the last 20 years, the prevalence of asthma has nearly doubled and now affects 8-10% of the population in the United States. Asthma also remains a major illness in terms of morbidity and suffering, and is the leading cause of hospitalizations in children under 15 years of age. Because asthma poses a lifelong burden to patients and society, efforts to increase the understanding of its pathogenesis are a key factor leading to its control and cure. Consequently, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of extramural experts, entitled "Future Research Directions in Asthma," on April 9-10, 2003, to identify research areas of greatest promise and opportunity in the field of asthma. The priority areas identified for research in asthma include: (1) innate immunity, adaptive immunity, and tolerance; (2) mechanisms and consequences of persistent asthma and asthma exacerbations; (3) airway remodeling: clinical consequences and reversibility (clinical relevance and resolution); (4) genetics/gene-environment interactions, pharmacogenetics; (5) intervention/prevention/therapeutics; and (6) vascular basis of asthma. JF - American Journal of Respiratory and Critical Care Medicine AU - Busse, William AU - Banks-Schlegel, Susan AU - Noel, Patricia AU - Ortega, Hector AU - et al Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 683 EP - 90 CY - New York PB - American Thoracic Society VL - 170 IS - 6 SN - 1073449X KW - Medical Sciences--Respiratory Diseases KW - United States KW - Humans KW - National Institutes of Health (U.S.) KW - Asthma -- genetics KW - Forecasting KW - Asthma -- therapy KW - Asthma -- immunology KW - Research -- trends KW - Asthma -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/199575912?accountid=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=conference&rft.jtitle=American+Journal+of+Respiratory+and+Critical+Care+Medicine&rft.atitle=Future+Research+Directions+in+Asthma+An+NHLBI+Working+Group+Report&rft.au=Busse%2C+William%3BBanks-Schlegel%2C+Susan%3BNoel%2C+Patricia%3BOrtega%2C+Hector%3Bet+al&rft.aulast=Busse&rft.aufirst=William&rft.date=2004-09-15&rft.volume=170&rft.issue=6&rft.spage=683&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 Central N1 - Copyright - Copyright American Thoracic Society Sep 15, 2004 N1 - Last updated - 2017-01-07 ER - TY - JOUR T1 - Cancer Incidence Among Pesticide Applicators Exposed to Atrazine in the Agricultural Health Study AN - 17861132; 6031526 AB - BACKGROUND: Atrazine is the most heavily applied agricultural pesticide for crop production in the United States. Both animal and human studies have suggested that atrazine is possibly carcinogenic, but results have been mixed. We evaluated cancer incidence in atrazine-exposed pesticide applicators among 53 943 participants in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. METHODS: We obtained detailed pesticide exposure information using a self-administered questionnaire completed at the time of enrollment (1993-1997). Cancer incidence was followed through December 31, 2001. We used adjusted Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) of multiple types of cancer among atrazine exposed applicators. P sub(trend) values were calculated using atrazine exposure as a continuous variable, and all statistical tests were two- sided. Two exposure metrics were used: quartiles of lifetime days of exposure and quartiles of intensity-weighted lifetime days of exposure. RESULTS: 36 513 (68%) applicators reported ever using atrazine; exposure was not associated with overall cancer incidence. Comparisons of cancer incidence in applicators with the highest atrazine exposure and those with the lowest exposure, assessed by lifetime days (RR sub(LD)) and intensity-weighted lifetime days (RR sub(IWLD)) of exposure yielded the following results: prostate cancer, RR sub(LD) = 0.88, 95% CI = 0.63 to 1.23, P sub(trend) = .26, and RR sub(IWLD) = 0.89, 95% CI = 0.63 to 1.25, P sub(trend) = .35; lung cancer, RR sub(LD) = 1.91, 95% CI = 0.93 to 3.94, P sub(trend) = .08, and RR sub(IWLD) = 1.37, 95% CI = 0.65 to 2.86, P sub(trend) = .19; bladder cancer, RR sub(LD) = 3.06, 95% CI = 0.86 to 10.81, P sub(trend) =.18, and RR sub(IWLD) = 0.85, 95% CI = 0.24 to 2.94, P sub(trend) = .71; non-Hodgkin lymphoma, RR sub(LD) = 1.61, 95% CI = 0.62 to 4.16, P sub(trend) = .35, and RR sub(IWLD) = 1.75, 95% CI = 0.73 to 4.20, P sub(trend) = .14; and multiple myeloma, RR sub(LD) = 1.60, 95% CI = 0.37 to 7.01, P sub(trend) = .41, and RR sub(IWLD) = 2.17, 95% CI = 0.45 to 10.32, P sub(trend) = .21. CONCLUSIONS: Our analyses did not find any clear associations between atrazine exposure and any cancer analyzed. However, further studies are warranted for tumor types in which there was a suggestion of trend (lung, bladder, non-Hodgkin lymphoma, and multiple myeloma). JF - Journal of the National Cancer Institute AU - Rusiecki, Jennifer A AU - De Roos, Anneclaire AU - Lee, Won Jin AU - Dosemeci, Mustafa AU - Lubin, Jay H AU - Hoppin, Jane A AU - Blair, Aaron AU - Alavanja, Michael CR AD - Occupational and Environmental Epidemiology Branch and Biostatistics Branch, National Institutes of Health, Department of Health and Human Services, Rockville, MD Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 1375 EP - 1382 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 96 IS - 18 SN - 0027-8874, 0027-8874 KW - Health & Safety Science Abstracts KW - Pesticides KW - Atrazine KW - Agrochemicals KW - Cancer KW - Occupational exposure KW - H 5000:Pesticides UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17861132?accountid=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=Journal+of+the+National+Cancer+Institute&rft.atitle=Cancer+Incidence+Among+Pesticide+Applicators+Exposed+to+Atrazine+in+the+Agricultural+Health+Study&rft.au=Rusiecki%2C+Jennifer+A%3BDe+Roos%2C+Anneclaire%3BLee%2C+Won+Jin%3BDosemeci%2C+Mustafa%3BLubin%2C+Jay+H%3BHoppin%2C+Jane+A%3BBlair%2C+Aaron%3BAlavanja%2C+Michael+CR&rft.aulast=Rusiecki&rft.aufirst=Jennifer&rft.date=2004-09-15&rft.volume=96&rft.issue=18&rft.spage=1375&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Agrochemicals; Atrazine; Pesticides; Occupational exposure; Cancer ER - TY - JOUR T1 - Human In vivo Radiation-Induced Biomarkers: Gene Expression Changes in Radiotherapy Patients AN - 17798889; 6030313 AB - After initially identifying potential biomarkers of radiation exposure through microarray studies of ex vivo irradiated human peripheral white blood cells, we have now measured the in vivo responses of several of these biomarker genes in patients undergoing total body irradiation. Microarray analysis has identified additional in vivo radiation-responsive genes, although the general in vivo patterns of stress-gene induction appear similar to those obtained from ex vivo white blood cell experiments. Additional studies may reveal correlations between responses and either diagnosis or prognosis, and such in vivo validation marks an important step in the development of potentially informative radiation exposure biomarkers. JF - Cancer Research AU - Amundson, Sally A AU - Grace, Marcy B AU - McLeland, Christopher B AU - Epperly, Michael W AU - Yeager, Andrew AU - Zhan, Qimin AU - Greenberger, Joel S AU - Fornace, Albert J AD - Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 6368 EP - 6371 PB - Maclean-Hunter Ltd. VL - 64 IS - 18 SN - 0008-5472, 0008-5472 KW - Biochemistry Abstracts 2: Nucleic Acids; Toxicology Abstracts KW - Gene expression KW - Radiation KW - Leukocytes KW - Prognosis KW - Radiotherapy KW - biomarkers KW - Cancer KW - X 24210:Radiation & radioactive materials KW - N 14045:Transcriptional regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17798889?accountid=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+Research&rft.atitle=Human+In+vivo+Radiation-Induced+Biomarkers%3A+Gene+Expression+Changes+in+Radiotherapy+Patients&rft.au=Amundson%2C+Sally+A%3BGrace%2C+Marcy+B%3BMcLeland%2C+Christopher+B%3BEpperly%2C+Michael+W%3BYeager%2C+Andrew%3BZhan%2C+Qimin%3BGreenberger%2C+Joel+S%3BFornace%2C+Albert+J&rft.aulast=Amundson&rft.aufirst=Sally&rft.date=2004-09-15&rft.volume=64&rft.issue=18&rft.spage=6368&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Gene expression; Radiation; Leukocytes; Prognosis; Radiotherapy; biomarkers; Cancer ER - TY - JOUR T1 - SJG-136 (NSC 694501), A Novel Rationally Designed DNA Minor Groove Interstrand Cross-Linking Agent with Potent and Broad Spectrum Antitumor Activity: Part 2: Efficacy Evaluations AN - 17739881; 6030452 AB - Pyrrolo[2,1-c][1,4]benzodiazepine dimer SJG-136 (NSC 694501) selectively cross-links guanine residues located on opposite strands of DNA, and exhibits potent in vitro cytotoxicity. In addition, SJG-136 is highly active in vivo in hollow fiber assays. In the current investigation, SJG-136 was evaluated for in vivo efficacy in 10 tumor models selected on the basis of sensitivity of cells grown in the hollow fiber and in vitro time course assays: LOX IMVI and UACC-62 (melanomas); OVCAR-3 and OVCAR-5 (ovarian carcinomas); MDA-MB-435 (breast carcinoma); SF-295 and C-6 (gliomas); LS-174T (colon carcinoma); HL-60 TB (promyelocytic leukemia); and NCI-H522 (lung carcinoma). SJG-136 was active against small (150 mg) and large (250-400 mg) xenografts with tumor mass reductions in all 10 models. In addition, significant growth delays occurred in nine models, cell kill in six models ranged between 1.9 and 7.2 logs, and there were 1 to 4/6 tumor-free responses in six models. SJG-136 is active following i.v. bolus injections, as well as by 5-day continuous infusions. Of all of the schedules tested, bolus administrations for 5 consecutive days (qdx5) conferred the greatest efficacy. SJG-136 is active over a wide dosage range in athymic mouse xenografts: on a qdx5 schedule, the maximum-tolerated dose was -120 mu g/kg/dose (total dose: 0.6 mg/kg = 1.8 mg/m super(2)) and the minimum effective dose in the most sensitive model (SF-295) was -16 mu g/kg/dose (total dose: 0.08 mg/kg = 0.24 mg/m super(2)). Results of this study extend the initial in vivo observations reported in the reference above and confirm the importance of expediting more detailed preclinical evaluations on this novel agent in support of phase I clinical trials in the United Kingdom and the United States, which are planned to commence shortly. JF - Cancer Research AU - Alley, Michael C AU - Hollingshead, Melinda G AU - Pacula-Cox, Christine M AU - Waud, William R AU - Hartley, John A AU - Howard, Philip W AU - Gregson, Stephen J AU - Thurston, David E AU - Sausville, Edward A AD - Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda and Frederick, Maryland Y1 - 2004/09/15/ PY - 2004 DA - 2004 Sep 15 SP - 6700 EP - 6706 PB - Maclean-Hunter Ltd. VL - 64 IS - 18 SN - 0008-5472, 0008-5472 KW - cross-linking KW - man KW - animal models KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Antitumor agents KW - Melanoma KW - DNA KW - Breast carcinoma KW - Ovarian carcinoma KW - Glioma KW - Xenografts KW - Antitumor activity KW - N 14025:RNA/DNA role in infection & immune response KW - W3 33374:Antitumor agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17739881?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=SJG-136+%28NSC+694501%29%2C+A+Novel+Rationally+Designed+DNA+Minor+Groove+Interstrand+Cross-Linking+Agent+with+Potent+and+Broad+Spectrum+Antitumor+Activity%3A+Part+2%3A+Efficacy+Evaluations&rft.au=Alley%2C+Michael+C%3BHollingshead%2C+Melinda+G%3BPacula-Cox%2C+Christine+M%3BWaud%2C+William+R%3BHartley%2C+John+A%3BHoward%2C+Philip+W%3BGregson%2C+Stephen+J%3BThurston%2C+David+E%3BSausville%2C+Edward+A&rft.aulast=Alley&rft.aufirst=Michael&rft.date=2004-09-15&rft.volume=64&rft.issue=18&rft.spage=6700&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 - DNA; Antitumor activity; Antitumor agents; Melanoma; Ovarian carcinoma; Xenografts; Breast carcinoma; Glioma ER - TY - JOUR T1 - Effect of D-penicillamine on neuromuscular junction in patients with Wilson disease. AN - 66876103; 15365158 JF - Neurology AU - Komal Kumar, R N AU - Patil, S A AU - Taly, A B AU - Nirmala, M AU - Sinha, S AU - Arunodaya, G R AD - Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India. Y1 - 2004/09/14/ PY - 2004 DA - 2004 Sep 14 SP - 935 EP - 936 VL - 63 IS - 5 KW - Autoantibodies KW - 0 KW - Receptors, Cholinergic KW - Penicillamine KW - GNN1DV99GX KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Autoantibodies -- blood KW - Autoantibodies -- immunology KW - Child KW - Prospective Studies KW - Single-Blind Method KW - Adult KW - Cohort Studies KW - Enzyme-Linked Immunosorbent Assay KW - Follow-Up Studies KW - Adolescent KW - Receptors, Cholinergic -- immunology KW - Female KW - Male KW - Penicillamine -- adverse effects KW - Neuromuscular Junction -- drug effects KW - Myasthenia Gravis -- immunology KW - Myasthenia Gravis -- chemically induced KW - Hepatolenticular Degeneration -- complications KW - Hepatolenticular Degeneration -- drug therapy KW - Penicillamine -- therapeutic use KW - Hepatolenticular Degeneration -- immunology KW - Myasthenia Gravis -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66876103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Effect+of+D-penicillamine+on+neuromuscular+junction+in+patients+with+Wilson+disease.&rft.au=Komal+Kumar%2C+R+N%3BPatil%2C+S+A%3BTaly%2C+A+B%3BNirmala%2C+M%3BSinha%2C+S%3BArunodaya%2C+G+R&rft.aulast=Komal+Kumar&rft.aufirst=R&rft.date=2004-09-14&rft.volume=63&rft.issue=5&rft.spage=935&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 - 2005-04-08 N1 - Date created - 2004-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. AN - 66870920; 15364958 AB - Bloom's syndrome is a rare autosomal recessive genetic disorder characterized by chromosomal aberrations, genetic instability, and cancer predisposition, all of which may be the result of abnormal signal transduction during DNA damage recognition. Here, we show that BLM is an intermediate responder to stalled DNA replication forks. BLM colocalized and physically interacted with the DNA damage response proteins 53BP1 and H2AX. Although BLM facilitated physical interaction between p53 and 53BP1, 53BP1 was required for efficient accumulation of both BLM and p53 at the sites of stalled replication. The accumulation of BLM/53BP1 foci and the physical interaction between them was independent of gamma-H2AX. The active Chk1 kinase was essential for both the accurate focal colocalization of 53BP1 with BLM and the consequent stabilization of BLM. Once the ATR/Chk1- and 53BP1-mediated signal from replicational stress is received, BLM functions in multiple downstream repair processes, thereby fulfilling its role as a caretaker tumor suppressor. JF - The Journal of cell biology AU - Sengupta, Sagar AU - Robles, Ana I AU - Linke, Steven P AU - Sinogeeva, Natasha I AU - Zhang, Ran AU - Pedeux, Remy AU - Ward, Irene M AU - Celeste, Arkady AU - Nussenzweig, André AU - Chen, Junjie AU - Halazonetis, Thanos D AU - Harris, Curtis C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 2004/09/13/ PY - 2004 DA - 2004 Sep 13 SP - 801 EP - 813 VL - 166 IS - 6 SN - 0021-9525, 0021-9525 KW - Carrier Proteins KW - 0 KW - Intracellular Signaling Peptides and Proteins KW - Phosphoproteins KW - RNA, Small Interfering KW - TP53BP1 protein, human KW - Tumor Suppressor p53-Binding Protein 1 KW - Protein Kinases KW - EC 2.7.- KW - CHEK1 protein, human KW - EC 2.7.11.1 KW - Checkpoint Kinase 1 KW - DNA Helicases KW - EC 3.6.4.- KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Hydroxyurea KW - X6Q56QN5QC KW - Index Medicus KW - Microscopy, Confocal KW - Fibroblasts -- drug effects KW - DNA Damage KW - Humans KW - Fibroblasts -- cytology KW - Hydroxyurea -- pharmacology KW - Precipitin Tests KW - Fibroblasts -- metabolism KW - Blotting, Western KW - Phosphorylation KW - Kinetics KW - Cell Line KW - Bromodeoxyuridine -- metabolism KW - Protein Kinases -- metabolism KW - DNA Helicases -- metabolism KW - DNA Helicases -- genetics KW - S Phase KW - Bloom Syndrome -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66870920?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+cell+biology&rft.atitle=Functional+interaction+between+BLM+helicase+and+53BP1+in+a+Chk1-mediated+pathway+during+S-phase+arrest.&rft.au=Sengupta%2C+Sagar%3BRobles%2C+Ana+I%3BLinke%2C+Steven+P%3BSinogeeva%2C+Natasha+I%3BZhang%2C+Ran%3BPedeux%2C+Remy%3BWard%2C+Irene+M%3BCeleste%2C+Arkady%3BNussenzweig%2C+Andr%C3%A9%3BChen%2C+Junjie%3BHalazonetis%2C+Thanos+D%3BHarris%2C+Curtis+C&rft.aulast=Sengupta&rft.aufirst=Sagar&rft.date=2004-09-13&rft.volume=166&rft.issue=6&rft.spage=801&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+cell+biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-25 N1 - Date created - 2004-09-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 2002 Apr 1;157(1):19-30 [11916980] J Cell Biol. 1999 Sep 6;146(5):905-16 [10477747] Cancer Res. 2002 May 15;62(10):2766-70 [12019152] Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8173-8 [12034884] J Biol Chem. 2002 Aug 23;277(34):30515-23 [12034743] Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14795-800 [12399544] Science. 2002 Nov 15;298(5597):1435-8 [12364621] Nat Cell Biol. 2002 Dec;4(12):998-1002 [12447382] Nat Cell Biol. 2002 Dec;4(12):993-7 [12447390] EMBO J. 2003 Mar 3;22(5):1210-22 [12606585] Nat Rev Cancer. 2003 Mar;3(3):169-78 [12612652] Mol Cell Biol. 2003 Apr;23(7):2556-63 [12640136] Cancer Cell. 2003 Mar;3(3):247-58 [12676583] Methods Mol Med. 2003;85:49-56 [12710196] Cancer Res. 2003 May 15;63(10):2596-605 [12750285] J Biol Chem. 2003 May 30;278(22):19579-82 [12697768] Cancer Cell. 2003 May;3(5):421-9 [12781359] J Cell Biol. 2003 Sep 29;162(7):1197-209 [14517203] Nature. 2003 Dec 18;426(6968):870-4 [14685245] Cancer Res. 2003 Dec 15;63(24):8586-91 [14695167] Genes Dev. 2000 Feb 1;14(3):289-300 [10673501] Genes Dev. 2000 Apr 15;14(8):927-39 [10783165] Cancer Res. 2000 Apr 15;60(8):2108-12 [10786669] Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6504-8 [10823897] Curr Biol. 2000 Jul 27-Aug 10;10(15):886-95 [10959836] Genes Dev. 2000 Nov 15;14(22):2855-68 [11090133] J Cell Biol. 2000 Dec 25;151(7):1381-90 [11134068] Mol Cell Biol. 2001 Mar;21(5):1719-29 [11238909] J Cell Biol. 2001 Apr 16;153(2):367-80 [11309417] J Cell Biol. 2001 Apr 30;153(3):613-20 [11331310] J Biol Chem. 2001 Jun 1;276(22):19375-81 [11278509] Oncogene. 2001 May 3;20(20):2551-8 [11420665] J Biol Chem. 2001 Aug 31;276(35):32948-55 [11399766] Genes Dev. 2001 Sep 1;15(17):2177-96 [11544175] Annu Rev Genomics Hum Genet. 2000;1:409-59 [11701636] J Biol Chem. 2002 Feb 8;277(6):4428-34 [11711532] Mol Cell Biol. 2004 Feb;24(3):1279-91 [14729972] J Biol Chem. 2004 Mar 12;279(11):9677-80 [14742437] Oncogene. 2004 May 6;23(21):3749-56 [15064730] Trends Genet. 2004 Jun;20(6):235-43 [15145576] J Biol Chem. 1988 Dec 25;263(36):19263-6 [2974036] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6098-102 [8016121] Science. 2002 May 3;296(5569):922-7 [11934988] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Atomic Architecture of a Gas Channel AN - 19815839; 6028701 AB - Both prokaryotic and eukaryotic cells need to be able to transport ammonia gas. In their Perspective, Knepper and Agre discuss an exciting study (Khademi et al.) that reports resolution of the crystallographic structure of a bacterial ammonia transport channel, AmtB, to an astonishing 1.35 angstroms, an amazing feat for an integral membrane protein. The structure reveals how ammonia is transported in bacteria and sheds light on how related ammonia transport proteins work in eukaryotic cells. JF - Science (Washington) AU - Knepper, Mark A AU - Agre, Peter AD - M. A. Knepper is in the Laboratory of Kidney and Electrolyte Metabolism, National Institutes of Health, Bethesda, MD 20892, USA, pagre@jhmi.edu Y1 - 2004/09/10/ PY - 2004 DA - 2004 Sep 10 SP - 1573 EP - 1574 PB - American Association for the Advancement of Science, 1200 New York Avenue, NW Washington DC 20005 USA, [mailto:membership@aaas.org], [URL:http://www.aaas.org] VL - 305 IS - 5690 SN - 0036-8075, 0036-8075 KW - Microbiology Abstracts B: Bacteriology KW - Ammonia KW - Membrane proteins KW - J 02330:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19815839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28Washington%29&rft.atitle=The+Atomic+Architecture+of+a+Gas+Channel&rft.au=Knepper%2C+Mark+A%3BAgre%2C+Peter&rft.aulast=Knepper&rft.aufirst=Mark&rft.date=2004-09-10&rft.volume=305&rft.issue=5690&rft.spage=1573&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/10.1126%2Fscience.1103191 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-05-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Ammonia; Membrane proteins DO - http://dx.doi.org/10.1126/science.1103191 ER - TY - JOUR T1 - Pathogenic Bacteria Prefer Heme AN - 18060337; 6028710 AB - Bloodletting by physicians before the era of antibiotics may seem like a barbaric practice, but it may have been of some benefit to patients suffering from bacterial infections. In her Perspective, Rouault explains that most bacteria depend on a source of iron to grow and survive inside their animal hosts. A new study (Skaar et al.) shows that the pathogenic bacterium Staphylococcus aureus uses several ingenious strategies to obtain iron from heme stored as hemoglobin in the red blood cells of its mammalian hosts. JF - Science (Washington) AU - Rouault, Tracey A AD - Section on Human Iron Metabolism, Cell Biology and Metabolism Branch, the National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA, trou@helix.nih.gov Y1 - 2004/09/10/ PY - 2004 DA - 2004 Sep 10 SP - 1577 EP - 1578 PB - American Association for the Advancement of Science, 1200 New York Avenue, NW Washington DC 20005 USA, [mailto:membership@aaas.org], [URL:http://www.aaas.org] VL - 305 IS - 5690 SN - 0036-8075, 0036-8075 KW - Microbiology Abstracts B: Bacteriology KW - Hemoglobin KW - Heme KW - Reviews KW - Gene clusters KW - Erythrocytes KW - Staphylococcus aureus KW - Iron KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18060337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28Washington%29&rft.atitle=Pathogenic+Bacteria+Prefer+Heme&rft.au=Rouault%2C+Tracey+A&rft.aulast=Rouault&rft.aufirst=Tracey&rft.date=2004-09-10&rft.volume=305&rft.issue=5690&rft.spage=1577&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/10.1126%2Fscience.1102975 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-05-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Hemoglobin; Heme; Reviews; Erythrocytes; Gene clusters; Iron; Staphylococcus aureus DO - http://dx.doi.org/10.1126/science.1102975 ER - TY - JOUR T1 - Novel Protein-Protein Interactions of the Yersinia pestis Type III Secretion System Elucidated with a Matrix Analysis by Surface Plasmon Resonance and Mass Spectrometry AN - 17824141; 6006590 AB - Binary complexes formed by components of the Yersinia pestis type III secretion system were investigated by surface plasmon resonance (SPR) and matrix-assisted laser desorption time-of-flight mass spectrometry. Pairwise interactions between 15 recombinant Yersinia outer proteins (Yops), regulators, and chaperones were first identified by SPR. Mass spectrometry confirmed over 80% of the protein-protein interactions suggested by SPR, and new binding partners were further characterized. The Yop secretion protein (Ysc) M2 of Yersinia enterocolitica and LcrQ of Y. pestis, formerly described as ligands only for the specific Yop chaperone (Syc) H, formed stable complexes with SycE. Additional previously unreported complexes of YscE with the translocation regulator protein TyeA and the thermal regulator protein YmoA and multiple potential protein contacts by YscE, YopK, YopH, and LcrH were also identified. Because only stably folded proteins were examined, the interactions we identified are likely to occur either before or after transfer through the injectosome to mammalian host cells and may have relevance to understanding disease processes initiated by the plague bacterium. JF - Journal of Biological Chemistry AU - Swietnicki, Wieslaw AU - O'Brien, Sarah AU - Holman, Kari AU - Cherry, Scott AU - Brueggemann, Ernst AU - Tropea, Joseph E AU - Hines, Harry B AU - Waugh, David S AU - Ulrich, Robert G AD - United States Army Medical Research Institute of Infectious Diseases and the Macromolecular Crystallography Laboratory, NCI, National Institutes of Health, Frederick, Maryland Y1 - 2004/09/10/ PY - 2004 DA - 2004 Sep 10 SP - 38693 EP - 38700 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 - 279 IS - 37 SN - 0021-9258, 0021-9258 KW - TyeA protein KW - YmoA protein KW - YopK protein KW - YscE protein KW - secretion system (type III) KW - Microbiology Abstracts B: Bacteriology KW - surface plasmon resonance KW - Chromosome translocations KW - Yersinia enterocolitica KW - Yersinia pestis KW - LcrH protein KW - Chaperones KW - Plague KW - Protein interaction KW - Mass spectroscopy KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17824141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Novel+Protein-Protein+Interactions+of+the+Yersinia+pestis+Type+III+Secretion+System+Elucidated+with+a+Matrix+Analysis+by+Surface+Plasmon+Resonance+and+Mass+Spectrometry&rft.au=Swietnicki%2C+Wieslaw%3BO%27Brien%2C+Sarah%3BHolman%2C+Kari%3BCherry%2C+Scott%3BBrueggemann%2C+Ernst%3BTropea%2C+Joseph+E%3BHines%2C+Harry+B%3BWaugh%2C+David+S%3BUlrich%2C+Robert+G&rft.aulast=Swietnicki&rft.aufirst=Wieslaw&rft.date=2004-09-10&rft.volume=279&rft.issue=37&rft.spage=38693&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - surface plasmon resonance; Chromosome translocations; LcrH protein; Chaperones; Plague; Mass spectroscopy; Protein interaction; Yersinia pestis; Yersinia enterocolitica ER - TY - JOUR T1 - Three-dimensional Solution Structure of the Cytoplasmic B Domain of the Mannitol Transporter II super(Mannitol) of the Escherichia coli Phosphotransferase System AN - 17821331; 6006639 AB - The solution structure of the cytoplasmic B domain of the mannitol (Mtl) transporter (II super(Mtl)) from the mannitol branch of the Escherichia coli phosphotransferase system has been solved by multidimensional NMR spectroscopy with extensive use of residual dipolar couplings. The ordered IIB super(Mtl) domain (residues 375-471 of II super(Mtl)) consists of a four-stranded parallel beta-sheet flanked by two helices (alpha sub(1) and alpha sub(3)) on one face and helix alpha sub(2) on the opposite face with a characteristic Rossmann fold comprising two right-handed beta sub(1)alpha sub(1)beta sub(2) and beta sub(3)alpha sub(2)beta sub(4) motifs. The active site loop is structurally very similar to that of the eukaryotic protein tyrosine phosphatases, with the active site cysteine (Cys- 384) primed in the thiolate state (pK sub(a) < 5.6) for nucleophilic attack at the phosphorylated histidine (His-554) of the IIA super(Mtl) domain through stabilization by hydrogen bonding interactions with neighboring backbone amide groups at positions i + 2/3/4 from Cys-384 and with the hydroxyl group of Ser- 391 at position i + 7. Modeling of the phosphorylated state of IIB super(Mtl) suggests that the phosphoryl group can be readily stabilized by hydrogen bonding interactions with backbone amides in the i + 2/4/5/6/7 positions as well as with the hydroxyl group of Ser390 at position i + 6. Despite the absence of any significant sequence identity, the structure of IIB super(Mtl) is remarkably similar to the structures of bovine protein tyrosine phosphatase (which contains two long insertions relative to IIB super(Mtl)) and the cytoplasmic B component of enzyme II super(Chb), which fulfills an analogous role to IIB super(Mtl) in the N,N'- diacetylchitobiose branch of the phosphotransferase system. All three proteins utilize a cysteine residue in the nucleophilic attack of a phosphoryl group covalently bound to another protein. JF - Journal of Biological Chemistry AU - Legler, Patricia M AU - Cai, Mengli AU - Peterkofsky, Alan AU - Clore, GMarius AD - Laboratory of Chemical Physics, NIDDK, National Institutes of Health and the Laboratory of Cell Biology, NHLBI, National Institutes of Health, Bethesda, Maryland Y1 - 2004/09/10/ PY - 2004 DA - 2004 Sep 10 SP - 39115 EP - 39121 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 - 279 IS - 37 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts B: Bacteriology KW - Protein structure KW - Protein kinase A KW - Mannitol KW - Hydrogen bonding KW - Cysteine KW - Histidine KW - Magnetic resonance spectroscopy KW - Escherichia coli KW - phosphotransferase KW - amides KW - Protein-tyrosine-phosphatase KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17821331?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Three-dimensional+Solution+Structure+of+the+Cytoplasmic+B+Domain+of+the+Mannitol+Transporter+II+super%28Mannitol%29+of+the+Escherichia+coli+Phosphotransferase+System&rft.au=Legler%2C+Patricia+M%3BCai%2C+Mengli%3BPeterkofsky%2C+Alan%3BClore%2C+GMarius&rft.aulast=Legler&rft.aufirst=Patricia&rft.date=2004-09-10&rft.volume=279&rft.issue=37&rft.spage=39115&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Protein structure; Protein kinase A; Cysteine; Hydrogen bonding; Mannitol; Magnetic resonance spectroscopy; Histidine; phosphotransferase; amides; Protein-tyrosine-phosphatase; Escherichia coli ER - TY - JOUR T1 - Finding fusion genes resulting from chromosome rearrangement by analyzing the expressed sequence databases. AN - 66858379; 15326299 AB - Chromosomal rearrangements resulting in gene fusions are frequently involved in carcinogenesis. Here, we describe a semiautomatic procedure for identifying fusion gene transcripts by using publicly available mRNA and EST databases. With this procedure, we have identified 96 transcript sequences that are derived from 60 known fusion genes. Also, 47 or more additional sequences appear to be derived from 20 or more previously unknown putative fusion genes. We have experimentally verified the presence of a previously unknown IRA1/RGS17 fusion in the breast cancer cell line MCF7. The fusion gene encodes the full-length RGS17 protein, a regulator of G protein-coupled signaling, under the control of the IRA1 gene promoter. This study demonstrates that databases of ESTs can be used to discover fusion genes resulting from structural rearrangement of chromosomes. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Hahn, Yoonsoo AU - Bera, Tapan Kumar AU - Gehlhaus, Kristen AU - Kirsch, Ilan R AU - Pastan, Ira H AU - Lee, Byungkook AD - Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA. Y1 - 2004/09/07/ PY - 2004 DA - 2004 Sep 07 SP - 13257 EP - 13261 VL - 101 IS - 36 SN - 0027-8424, 0027-8424 KW - BCAS3-BCAS4 fusion protein, human KW - 0 KW - Oncogene Proteins, Fusion KW - RNA, Messenger KW - Index Medicus KW - Humans KW - Databases as Topic KW - RNA, Messenger -- analysis KW - In Situ Hybridization, Fluorescence KW - Cell Line, Tumor KW - Reverse Transcriptase Polymerase Chain Reaction KW - Female KW - Oncogene Proteins, Fusion -- genetics KW - Chromosome Aberrations KW - Expressed Sequence Tags UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66858379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Finding+fusion+genes+resulting+from+chromosome+rearrangement+by+analyzing+the+expressed+sequence+databases.&rft.au=Hahn%2C+Yoonsoo%3BBera%2C+Tapan+Kumar%3BGehlhaus%2C+Kristen%3BKirsch%2C+Ilan+R%3BPastan%2C+Ira+H%3BLee%2C+Byungkook&rft.aulast=Hahn&rft.aufirst=Yoonsoo&rft.date=2004-09-07&rft.volume=101&rft.issue=36&rft.spage=13257&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 - 2004-09-30 N1 - Date created - 2004-09-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Cancer. 2000 Nov;83(10):1309-17 [11044355] J Biol Chem. 1999 Apr 16;274(16):11060-71 [10196189] J Biol Chem. 2001 May 11;276(19):16561-6 [11278528] Mol Cell. 2002 Jul;10(1):21-33 [12150904] Genes Chromosomes Cancer. 2002 Dec;35(4):311-7 [12378525] J Cell Sci. 2002 Dec 1;115(Pt 23):4483-93 [12414994] Oncogene. 2002 Dec 9;21(56):8652-67 [12476311] Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16899-903 [12477932] Nucleic Acids Res. 2003 Feb 15;31(4):e17 [12582262] EMBO J. 2003 Mar 17;22(6):1336-46 [12628926] Cancer Res. 2003 Dec 15;63(24):8634-47 [14695175] Nat Genet. 2004 Jan;36(1):40-5 [14702039] Sci STKE. 2004 Jan 20;2004(216):re2 [14734786] Brain Res Mol Brain Res. 2004 Mar 17;122(1):24-34 [14992813] Nat Rev Cancer. 2004 Mar;4(3):177-83 [14993899] Nat Genet. 2004 Apr;36(4):331-4 [15054488] Curr Pharm Des. 2004;10(16):1937-58 [15180530] J Biol Chem. 2004 Jun 18;279(25):26314-22 [15096504] Clin Genet. 1975 Aug;8(2):112-6 [1175316] Science. 1982 Apr 16;216(4543):301-3 [6801764] Am J Med Genet. 1994 Nov 15;53(3):255-63 [7856662] Genome Res. 1998 Sep;8(9):967-74 [9750195] Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12185-90 [9770461] Genome Res. 2001 Mar;11(3):422-35 [11230166] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - PCR expression mutagenesis: a high-throughput mutation assay applied to the glucocorticoid receptor ligand-binding domain. AN - 66864668; 15358110 AB - Glucocorticoid receptors (GRs) are extensively studied members of the steroid hormone receptor superfamily that regulate the transcription rates of numerous genes. Notwithstanding, the role of each GR amino acid in the various steps of transactivation is still unknown. A recent report shows that linear DNA has the same capacity as super-helical plasmid DNA for gene expression in transient transfection assays. Based on this observation, we describe a high-throughput assay to analyze a large set of alanine point mutations that are introduced by two rounds of PCR. The PCR products are then directly transfected into cells. This PCR expression mutagenesis (PEM) technique is used to identify several new residues of the GR ligand binding domain that influence ligand binding and/or transactivation. PEM thus provides a quick method for screening large quantities of mutant proteins. In combination with automation, PEM provides a more rapid and efficient tool for probing the role of each amino acid in the biological functions of a given protein. JF - Biochemical and biophysical research communications AU - Chen, Jun AU - Blackford, John A AU - Simons, S Stoney AD - Steroid Hormones Section, NIDDK/LMCB, National Institutes of Health, Bethesda, MD, USA. jchen@usuhs.mil Y1 - 2004/09/03/ PY - 2004 DA - 2004 Sep 03 SP - 893 EP - 899 VL - 321 IS - 4 SN - 0006-291X, 0006-291X KW - Ligands KW - 0 KW - Receptors, Glucocorticoid KW - Recombinant Proteins KW - Index Medicus KW - Animals KW - COS Cells KW - Models, Molecular KW - Recombinant Proteins -- genetics KW - Transcriptional Activation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Point Mutation KW - Binding Sites -- genetics KW - Recombinant Proteins -- chemistry KW - Protein Structure, Tertiary KW - Cell Line KW - Receptors, Glucocorticoid -- chemistry KW - Polymerase Chain Reaction -- methods KW - Receptors, Glucocorticoid -- metabolism KW - Receptors, Glucocorticoid -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66864668?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=PCR+expression+mutagenesis%3A+a+high-throughput+mutation+assay+applied+to+the+glucocorticoid+receptor+ligand-binding+domain.&rft.au=Chen%2C+Jun%3BBlackford%2C+John+A%3BSimons%2C+S+Stoney&rft.aulast=Chen&rft.aufirst=Jun&rft.date=2004-09-03&rft.volume=321&rft.issue=4&rft.spage=893&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 - 2004-10-14 N1 - Date created - 2004-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serious ophthalmic pathology compromising vision in HCV/HIV co-infected patients treated with peginterferon alpha-2b and ribavirin. AN - 66795582; 15316341 AB - To characterize the ocular changes associated with peginterferon alpha 2b (peg-IFN alpha-2b) and ribavirin therapy for chronic hepatitis C infection in HIV co-infected individuals. A prospective, open-label trial treating HIV/hepatitis C (HCV) co-infected individuals with peg-IFN alpha-2b and ribavirin at the Warren Grant Magnusson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Twenty-three patients with a high mean CD4+ T-cell count were treated with peg-IFN alpha-2b and ribavirin and followed for 40 to 88 weeks. Ophthalmologic evaluations including visual acuity, visual field testing, color vision examination and indirect ophthalmoscopy were performed at baseline and every 3 months. Eight of the 23 patients (35%) developed ophthalmologic pathology, including cotton wool spots, cataracts, and two patients developed decreased color vision. These two patients regained their color vision, one after cessation of anti-HCV therapy. Although retinal pathologies have been reported in patients treated with interferon-alpha, they have not been reported during peg-IFN alpha-2b therapy nor in HIV/HCV co-infected patients. The incidence of serious ocular pathology associated with anti-HCV therapy may be very high and is probably associated with peg-IFN alpha-2b. Increased monitoring of patients treated with peg-IFN alpha-2b for retinal and visual changes is warranted. JF - AIDS (London, England) AU - Farel, Claire AU - Suzman, Daniel L AU - McLaughlin, Mary AU - Campbell, Colleen AU - Koratich, Chad AU - Masur, Henry AU - Metcalf, Julia A AU - Robinson, Michael R AU - Polis, Michael A AU - Kottilil, Shyam AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. Y1 - 2004/09/03/ PY - 2004 DA - 2004 Sep 03 SP - 1805 EP - 1809 VL - 18 IS - 13 SN - 0269-9370, 0269-9370 KW - Interferon-alpha KW - 0 KW - Recombinant Proteins KW - Polyethylene Glycols KW - 30IQX730WE KW - interferon alfa-2b KW - 43K1W2T1M6 KW - Ribavirin KW - 49717AWG6K KW - peginterferon alfa-2b KW - G8RGG88B68 KW - Index Medicus KW - AIDS/HIV KW - Color Vision Defects -- chemically induced KW - Prospective Studies KW - Humans KW - Cataract -- chemically induced KW - Adult KW - Middle Aged KW - Vision Disorders -- chemically induced KW - Interferon-alpha -- adverse effects KW - HIV Infections -- complications KW - Hepatitis C, Chronic -- drug therapy KW - Eye Diseases -- chemically induced KW - Ribavirin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66795582?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Serious+ophthalmic+pathology+compromising+vision+in+HCV%2FHIV+co-infected+patients+treated+with+peginterferon+alpha-2b+and+ribavirin.&rft.au=Farel%2C+Claire%3BSuzman%2C+Daniel+L%3BMcLaughlin%2C+Mary%3BCampbell%2C+Colleen%3BKoratich%2C+Chad%3BMasur%2C+Henry%3BMetcalf%2C+Julia+A%3BRobinson%2C+Michael+R%3BPolis%2C+Michael+A%3BKottilil%2C+Shyam&rft.aulast=Farel&rft.aufirst=Claire&rft.date=2004-09-03&rft.volume=18&rft.issue=13&rft.spage=1805&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 - 2004-11-22 N1 - Date created - 2004-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced Postischemic Functional Recovery in CYP2J2 Transgenic Hearts Involves Mitochondrial ATP-Sensitive K super(+) Channels and p42/p44 MAPK Pathway AN - 17743024; 6025776 AB - Human CYP2J2 is abundant in heart and active in the biosynthesis of epoxyeicosatrienoic acids (EETs); however, the functional role of this P450 and its eicosanoid products in the heart remains unknown. Transgenic mice with cardiomyocyte-specific overexpression of CYP2J2 were generated. CYP2J2 transgenic (Tr) mice have normal heart anatomy and basal contractile function. CYP2J2 Tr hearts have improved recovery of left ventricular developed pressure (LVDP) compared with wild-type (WT) hearts after 20 minutes ischemia and 40 minutes reperfusion. Perfusion with the selective P450 epoxygenase inhibitor N- methylsulphonyl-6-(2-proparglyloxyphenyl)hexanamide (MS-PPOH) for 20 minutes before ischemia results in reduced postischemic LVDP recovery in WT hearts and abolishes the improved postischemic LVDP recovery in CYP2J2 Tr hearts. Perfusion with the ATP-sensitive K super(+) channel (K sub(ATP)) inhibitor glibenclamide (GLIB) or the mitochondrial K sub(ATP) (mitoK sub(ATP)) inhibitor 5-hydroxydecanoate (5-HD) for 20 minutes before ischemia abolishes the cardioprotective effects of CYP2J2 overexpression. Flavoprotein fluorescence, a marker of mitoK sub(ATP) activity, is higher in cardiomyocytes from CYP2J2 Tr versus WT mice. Moreover, CYP2J2-derived EETs (1 to 5 mu mol/L) increase flavoprotein fluorescence in WT cardiomyocytes. CYP2J2 Tr mice exhibit increased expression of phospho-p42/p44 mitogen-activated protein kinase (MAPK) after ischemia, and addition of the p42/p44 MAPK kinase (MEK) inhibitor PD98059 during reperfusion abolishes the cardioprotective effects of CYP2J2 overexpression. Together, these data suggest that CYP2J2- derived metabolites are cardioprotective after ischemia, and the mechanism for this cardioprotection involves activation of mitoK sub(ATP) and p42/p44 MAPK. JF - Circulation Research AU - Seubert, John AU - Yang, Baichun AU - Bradbury, JAlyce AU - Graves, Joan AU - Degraff, Laura M AU - Gabel, Scott AU - Gooch, Rebecca AU - Foley, Julie AU - Newman, John AU - Mao, Lan AU - Rockman, Howard A AU - Hammock, Bruce D AU - Murphy, Elizabeth AU - Zeldin, Darryl C AD - Division of Intramural Research (J.S., B.Y., J.A.B., J.G., L.M.D, S.G., R.G., J.F., E.M., D.C.Z.), NIEHS/NIH, Research Triangle Park, NC Y1 - 2004/09/03/ PY - 2004 DA - 2004 Sep 03 SP - 506 EP - 514 PB - Lippincott Williams & Wilkins, Inc, 530 Walnut Street Philadelphia PA 19106-3621 USA, [URL:http://www.lww.com/] VL - 95 IS - 5 SN - 0009-7330, 0009-7330 KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Heart KW - Mitochondria KW - Contraction KW - Protein kinase KW - Potassium channels KW - W3 33056:Animal models of human disease KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17743024?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation+Research&rft.atitle=Enhanced+Postischemic+Functional+Recovery+in+CYP2J2+Transgenic+Hearts+Involves+Mitochondrial+ATP-Sensitive+K+super%28%2B%29+Channels+and+p42%2Fp44+MAPK+Pathway&rft.au=Seubert%2C+John%3BYang%2C+Baichun%3BBradbury%2C+JAlyce%3BGraves%2C+Joan%3BDegraff%2C+Laura+M%3BGabel%2C+Scott%3BGooch%2C+Rebecca%3BFoley%2C+Julie%3BNewman%2C+John%3BMao%2C+Lan%3BRockman%2C+Howard+A%3BHammock%2C+Bruce+D%3BMurphy%2C+Elizabeth%3BZeldin%2C+Darryl+C&rft.aulast=Seubert&rft.aufirst=John&rft.date=2004-09-03&rft.volume=95&rft.issue=5&rft.spage=506&rft.isbn=&rft.btitle=&rft.title=Circulation+Research&rft.issn=00097330&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 - Protein kinase; Potassium channels; Heart; Contraction; Mitochondria ER - TY - JOUR T1 - Role of extracellular histidines in antagonist sensitivity of the rat P2X4 receptor. AN - 66818940; 15331152 AB - The pharmacological property that most distinguishes rat P2X4 receptors from other P2X receptors is their insensitivity to the purinoceptor antagonists, suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). The molecular basis of this insensitivity is not known. Here, we investigated the possibility that histidine residues in the extracellular loop of P2X4 receptors may be involved in the antagonist sensitivity of these receptors. We found that histidine mutation H241A in the rat P2X4 receptor produced receptors that are sensitive to suramin and PPADS. In contrast, mutation H140A or H286A did not significantly alter antagonist sensitivity. In addition, mutation H241A in the human P2X4 receptor significantly increased antagonist sensitivity. The results suggest that histidine 241of P2X4 receptors is involved in regulating the antagonist sensitivity of these receptors. JF - Neuroscience letters AU - Xiong, Keming AU - Stewart, Randall R AU - Weight, Forrest F AU - Li, Chaoying AD - Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892-8115, USA. Y1 - 2004/09/02/ PY - 2004 DA - 2004 Sep 02 SP - 197 EP - 200 VL - 367 IS - 2 SN - 0304-3940, 0304-3940 KW - P2RX4 protein, human KW - 0 KW - P2rx4 protein, rat KW - Purinergic P2 Receptor Antagonists KW - Receptors, Purinergic P2 KW - Receptors, Purinergic P2X4 KW - pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid KW - 149017-66-3 KW - Histidine KW - 4QD397987E KW - Pyridoxal Phosphate KW - 5V5IOJ8338 KW - Suramin KW - 6032D45BEM KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Index Medicus KW - Patch-Clamp Techniques -- methods KW - Animals KW - Analysis of Variance KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Humans KW - Membrane Potentials -- physiology KW - Suramin -- pharmacology KW - Rats KW - Transfection -- methods KW - Mutagenesis, Site-Directed -- physiology KW - Xenopus KW - Oocytes KW - Membrane Potentials -- drug effects KW - Adenosine Triphosphate -- pharmacology KW - Extracellular Space -- metabolism KW - Receptors, Purinergic P2 -- metabolism KW - Pyridoxal Phosphate -- pharmacology KW - Pyridoxal Phosphate -- analogs & derivatives KW - Extracellular Space -- drug effects KW - Histidine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66818940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Role+of+extracellular+histidines+in+antagonist+sensitivity+of+the+rat+P2X4+receptor.&rft.au=Xiong%2C+Keming%3BStewart%2C+Randall+R%3BWeight%2C+Forrest+F%3BLi%2C+Chaoying&rft.aulast=Xiong&rft.aufirst=Keming&rft.date=2004-09-02&rft.volume=367&rft.issue=2&rft.spage=197&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 - 2004-11-15 N1 - Date created - 2004-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response AN - 18056619; 5998308 AB - Fifty million new infections with Mycobacterium tuberculosis occur annually, claiming 2-3 million lives from tuberculosis worldwide. Despite the apparent lack of significant genetic heterogeneity between strains of M. tuberculosis, there is mounting evidence that considerable heterogeneity exists in molecules important in disease pathogenesis. These differences may manifest in the ability of some isolates to modify the host cellular immune response, thereby contributing to the observed diversity of clinical outcomes. Here we describe the identification and functional relevance of a highly biologically active lipid species: a polyketide synthase-derived phenolic glycolipid (PGL) produced by a subset of M. tuberculosis isolates belonging to the W-Beijing family that show 'hyperlethality' in murine disease models. Disruption of PGL synthesis results in loss of this hypervirulent phenotype without significantly affecting bacterial load during disease. Loss of PGL was found to correlate with an increase in the release of the pro-inflammatory cytokines tumour-necrosis factor- alpha and interleukins 6 and 12 in vitro. Furthermore, the overproduction of PGL by M. tuberculosis or the addition of purified PGL to monocyte-derived macrophages was found to inhibit the release of these pro-inflammatory mediators in a dose-dependent manner. JF - Nature AU - Reed, Michael B AU - Domenech, Pilar AU - Manca, Claudia AU - Su, Hua AU - Barczak, Amy K AU - Kreiswirth, Barry N AU - Kaplan, Gilla AU - Barry, Clifton E AD - Tuberculosis Research Section, NIAID, National Institutes of Health, 12441 Parklawn Drive, Rockville, Maryland 20852, USA, clifton_barry@nih.gov Y1 - 2004/09/02/ PY - 2004 DA - 2004 Sep 02 SP - 84 EP - 87 PB - Nature Publishing Group, The Macmillan Building 4 Crinan Street London N1 9XW UK, [mailto:feedback@nature.com], [URL:http://www.nature.com/] VL - 431 IS - 7004 SN - 0028-0836, 0028-0836 KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Interleukin 6 KW - Macrophages KW - Tumor necrosis factor-a KW - Inflammation KW - Glycolipids KW - Interleukin 12 KW - Tumor necrosis factor-^a KW - Tuberculosis KW - Mycobacterium tuberculosis KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18056619?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=A+glycolipid+of+hypervirulent+tuberculosis+strains+that+inhibits+the+innate+immune+response&rft.au=Reed%2C+Michael+B%3BDomenech%2C+Pilar%3BManca%2C+Claudia%3BSu%2C+Hua%3BBarczak%2C+Amy+K%3BKreiswirth%2C+Barry+N%3BKaplan%2C+Gilla%3BBarry%2C+Clifton+E&rft.aulast=Reed&rft.aufirst=Michael&rft.date=2004-09-02&rft.volume=431&rft.issue=7004&rft.spage=84&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2Fnature02837 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium tuberculosis; Inflammation; Macrophages; Tumor necrosis factor-a; Interleukin 6; Interleukin 12; Tuberculosis; Glycolipids; Tumor necrosis factor-^a DO - http://dx.doi.org/10.1038/nature02837 ER - TY - JOUR T1 - Recombinant human activated protein C in sepsis: previous concerns and current usage AN - 888093868; 14610340 AB - Recombinant human activated protein C (rhAPC) was approved by the FDA for clinical use in severely septic patients approximately 2 years ago. This approval, based upon the results of the Phase III clinical trial, Phase III Protein C Worldwide Evaluation in Severe Sepsis (PROWESS), was not without opposition as concerns regarding rhAPCE14s inconsistent effects during the trial, incomplete understanding of its mechanism of action, and its safety profile within various subgroups were questioned during the FDAE14s evaluation. In light of these concerns, we have attempted to assess rhAPCE14s cost effectiveness by first comparing its performance in recent clinical use to that of the Phase III trial and then by examining other potentially less expensive treatments with effects that may overlap with rhAPC. Recent postmarketing analysis suggests a higher mortality rate in patients with similar disease severity (number of injured organs) during the clinical use of rhAPC when compared with the Phase III trial. Furthermore, the clinical use of rhAPC may also be associated with a higher incidence of bleeding risk or other adverse events that necessitate the discontinuation of treatment with rhAPC. A recent meta-analysis and other Phase III trials assessing agents with antithrombotic or anti-inflammatory properties, suggest that both heparin and physiologic-dose steroids may offer less expensive alternatives to rhAPC. The results of recently completed and ongoing Phase IV trials will be helpful in defining rhAPCE14s role in the treatment of sepsis. JF - Therapy AU - Haley, Michael AU - Cui, Xizhong AU - Minneci, Peter C AU - Deans, Katherine J AU - Natanson, Charles AU - Eichacker, Peter Q AD - Critical Care Medicine Department, National Institutes of Health, Building 10, Room 7D43, Bethesda, MD 20892, USA., PEichacker@cc.nih.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 123 EP - 129 PB - Future Science Group (FSG), Unitec House, 2 Albert Place London N3 1QB UK VL - 1 IS - 1 SN - 1475-0708, 1475-0708 KW - Microbiology Abstracts B: Bacteriology KW - Mortality KW - Sepsis KW - activated protein C KW - Reviews KW - Bleeding KW - Steroid hormones KW - Clinical trials KW - Antiinflammatory agents KW - Heparin KW - J 02400:Human Diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/888093868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Therapy&rft.atitle=Recombinant+human+activated+protein+C+in+sepsis%3A+previous+concerns+and+current+usage&rft.au=Haley%2C+Michael%3BCui%2C+Xizhong%3BMinneci%2C+Peter+C%3BDeans%2C+Katherine+J%3BNatanson%2C+Charles%3BEichacker%2C+Peter+Q&rft.aulast=Haley&rft.aufirst=Michael&rft.date=2004-09-01&rft.volume=1&rft.issue=1&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Therapy&rft.issn=14750708&rft_id=info:doi/10.2217%2F14750708.1.1.123 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-09-01 N1 - Last updated - 2012-03-29 N1 - SubjectsTermNotLitGenreText - Mortality; activated protein C; Sepsis; Reviews; Bleeding; Steroid hormones; Heparin; Antiinflammatory agents; Clinical trials DO - http://dx.doi.org/10.2217/14750708.1.1.123 ER - TY - JOUR T1 - Diet-gene interactions in p53-deficient mice: insulin-like growth factor-1 as a mechanistic target. AN - 66826841; 15333746 AB - Progress in cancer prevention research is being facilitated by the use of animal models displaying specific genetic susceptibilities for cancer, such as mice deficient in one (+/-) or both (-/-) alleles of the p53 tumor suppressor gene. Our lab, which focuses on nutrition (particularly energy balance/obesity) and molecular carcinogenesis, has shown in p53-/- mice that calorie restriction (CR) increases the latency of spontaneous tumor development (mostly lymphomas) approximately 75%, decreases serum insulin-like growth factor (IGF)-1 and leptin levels, and induces apoptosis in immature (lymphoma-susceptible) thymocytes. In heterozygous p53-deficient (p53+/-) mice, CR and a one day/wk fast each significantly delay spontaneous tumor development (a mix of lymphomas, sarcomas, and epithelial tumors) and decreases serum IGF-1 and leptin levels, even when begun late in life. We are presently comparing and combining CR and exercise (treadmill and running wheel) to further elucidate the relationships between energy balance, p53, and tumorigenesis in these models. Furthermore, we have capitalized on the susceptibility of p53+/- mice to chronic, low-dose aromatic amine-induced bladder carcinogenesis to develop a model for evaluating bladder cancer prevention approaches. Using this model, we have established that IGF-1 mediates many of the anti-cancer effects of CR. We are currently conducting oligonucleotide microarray studies to further characterize diet-gene interactions underlying the anti-cancer effects of CR and to determine which of the CR-responsive genes are IGF-1 dependent. JF - The Journal of nutrition AU - Hursting, Stephen D AU - Lavigne, Jackie A AU - Berrigan, David AU - Donehower, Lawrence A AU - Davis, Barbara J AU - Phang, James M AU - Barrett, J Carl AU - Perkins, Susan N AD - Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. hurstins@mail.nih.gov Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 2482S EP - 2486S VL - 134 IS - 9 SN - 0022-3166, 0022-3166 KW - Tumor Suppressor Protein p53 KW - 0 KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Index Medicus KW - Animals KW - Mice KW - Mice, Knockout KW - Genes KW - Insulin-Like Growth Factor I -- metabolism KW - Diet KW - Tumor Suppressor Protein p53 -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66826841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=Diet-gene+interactions+in+p53-deficient+mice%3A+insulin-like+growth+factor-1+as+a+mechanistic+target.&rft.au=Hursting%2C+Stephen+D%3BLavigne%2C+Jackie+A%3BBerrigan%2C+David%3BDonehower%2C+Lawrence+A%3BDavis%2C+Barbara+J%3BPhang%2C+James+M%3BBarrett%2C+J+Carl%3BPerkins%2C+Susan+N&rft.aulast=Hursting&rft.aufirst=Stephen&rft.date=2004-09-01&rft.volume=134&rft.issue=9&rft.spage=2482S&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 - 2004-10-14 N1 - Date created - 2004-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk factors for heart failure. AN - 66823601; 15331311 AB - Despite remarkable therapeutic advances in the management of patients with heart failure (HF), the mortality due to this syndrome remains high. Identifying free-living individuals who are at high risk for developing HF may allow implementing strategies that can prevent HF. Prospective epidemiologic studies have identified several risk factors and risk markers for HF. This article reviews current knowledge regarding conventional and newer risk markers for HF, outlines possible underlying mechanisms for the increased HF risk, and provides a framework for clinical multivariate risk prediction using HF risk factors. JF - The Medical clinics of North America AU - Kenchaiah, Satish AU - Narula, Jagat AU - Vasan, Ramachandran S AD - The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 1145 EP - 1172 VL - 88 IS - 5 SN - 0025-7125, 0025-7125 KW - Biomarkers KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Heart Valve Diseases -- complications KW - Humans KW - Smoking -- adverse effects KW - Biomarkers -- urine KW - Predictive Value of Tests KW - Risk Assessment KW - Obesity -- complications KW - Multivariate Analysis KW - Age Distribution KW - Hypertension -- complications KW - Sleep Apnea Syndromes -- complications KW - Epidemiologic Studies KW - Risk Factors KW - Myocardial Infarction -- complications KW - Kidney Diseases -- complications KW - Hypertrophy, Left Ventricular -- complications KW - Hyperlipidemias -- complications KW - Sex Distribution KW - Alcoholism -- complications KW - Biomarkers -- blood KW - Male KW - Diabetes Complications KW - Female KW - Heart Failure -- etiology KW - Heart Failure -- prevention & control KW - Heart Failure -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66823601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Medical+clinics+of+North+America&rft.atitle=Risk+factors+for+heart+failure.&rft.au=Kenchaiah%2C+Satish%3BNarula%2C+Jagat%3BVasan%2C+Ramachandran+S&rft.aulast=Kenchaiah&rft.aufirst=Satish&rft.date=2004-09-01&rft.volume=88&rft.issue=5&rft.spage=1145&rft.isbn=&rft.btitle=&rft.title=The+Medical+clinics+of+North+America&rft.issn=00257125&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-10-14 N1 - Date created - 2004-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Particulate matter from tobacco versus diesel car exhaust: an educational perspective. AN - 66822815; 15333875 AB - Air pollution is a common alibi used by adolescents taking up smoking and by smokers uncertain about quitting. However, environmental tobacco smoke (ETS) causes fine particulate matter (PM) indoor pollution exceeding outdoor limits, while new engines and fuels have reduced particulate emissions by cars. Data comparing PM emission from ETS and a recently released diesel car are presented. A 60 m3 garage was chosen to assess PM emission from three smouldering cigarettes (lit sequentially for 30 minutes) and from a TDCi 2000cc, idling for 30 minutes. Particulate was measured with a portable analyser with readings every two minutes. Background PM10, PM2.5, and PM1 levels (mean (SD)) were 15 (1), 13 (0.7), and 7 (0.6) microg/m3 in the car experiment and 36 (2), 28 (1), and 14 (0.8) microg/m3 in the ETS experiment, respectively. Mean (SD) PM recorded in the first hour after starting the engine were 44 (9), 31 (5), and 13 (1) microg/m3, while mean PM in the first hour after lighting cigarettes were 343 (192), 319 (178), and 168 (92) microg/m3 for PM(10), PM2.5, and PM1, respectively (p < 0.001, background corrected). ETS is a major source of PM pollution, contributing to indoor PM concentrations up to 10-fold those emitted from an idling ecodiesel engine. Besides its educational usefulness, this knowledge should also be considered from an ecological perspective. JF - Tobacco control AU - Invernizzi, G AU - Ruprecht, A AU - Mazza, R AU - Rossetti, E AU - Sasco, A AU - Nardini, S AU - Boffi, R AD - Tobacco Control Unit, National Cancer Institute SIMG-Italian Academy of GPs, Milan, Italy. ginverni@clavis.it Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 219 EP - 221 VL - 13 IS - 3 KW - Air Pollutants KW - 0 KW - Tobacco Smoke Pollution KW - Vehicle Emissions KW - Index Medicus KW - Tobacco Smoke Pollution -- analysis KW - Air Pollutants -- analysis KW - Vehicle Emissions -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66822815?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Tobacco+control&rft.atitle=Particulate+matter+from+tobacco+versus+diesel+car+exhaust%3A+an+educational+perspective.&rft.au=Invernizzi%2C+G%3BRuprecht%2C+A%3BMazza%2C+R%3BRossetti%2C+E%3BSasco%2C+A%3BNardini%2C+S%3BBoffi%2C+R&rft.aulast=Invernizzi&rft.aufirst=G&rft.date=2004-09-01&rft.volume=13&rft.issue=3&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Tobacco+control&rft.issn=1468-3318&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-04-15 N1 - Date created - 2004-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Introduction and overview. Perinatal carcinogenesis: growing a node for epidemiology, risk management, and animal studies. AN - 66794598; 15313581 AB - Perinatal carcinogenesis as a cross-disciplinary concern is the subject of this special issue of Toxicology and Applied Pharmacology, which consists of a total of eight reviews or commentaries in the areas of epidemiology, risk assessment, and animal models. Some of the conclusions from these articles, and the Questions and Answers section that follows most of them, are summarized here. There is adequate reason to suspect that perinatal exposures contribute to human cancer risk, both childhood cancers, and those appearing later in life. The latter type of risk may actually be quantitatively the more important, and involve a wide range of types of effects, but has received only limited attention. With regard to childhood cancers, fetal irradiation and diethylstilbestrol exposure are known etiological agents, and it is likely, but not yet certain, there are additional external causes of a portion of these. Some current focal points of interest here include nitroso compounds, DNA topoisomerase inhibitors, viruses, anti-AIDS drugs, and endocrine disruptors. Regulatory agencies must rely heavily on animal data for estimation of human risk due to perinatal exposures to chemicals, and the quantity and quality of these data presently available for this purpose are greatly limiting. Correctly designed conventional animal studies with suspect chemicals are still needed. Furthermore, genetically engineered mouse models for childhood cancers, especially medulloblastoma, have become available, and could be used for screening of candidate causative agents for this cancer type, and for better understanding of gene-environment interactions. JF - Toxicology and applied pharmacology AU - Anderson, Lucy M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702, USA. Andersol@mail.ncifcrf.gov Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 85 EP - 90 VL - 199 IS - 2 SN - 0041-008X, 0041-008X KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Neoplasms, Radiation-Induced -- epidemiology KW - Humans KW - Risk Management KW - Infant, Newborn KW - Environmental Exposure KW - Disease Models, Animal KW - Research KW - Neoplasms -- chemically induced KW - Neoplasms -- epidemiology KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66794598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Introduction+and+overview.+Perinatal+carcinogenesis%3A+growing+a+node+for+epidemiology%2C+risk+management%2C+and+animal+studies.&rft.au=Anderson%2C+Lucy+M&rft.aulast=Anderson&rft.aufirst=Lucy&rft.date=2004-09-01&rft.volume=199&rft.issue=2&rft.spage=85&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 - 2004-09-20 N1 - Date created - 2004-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perinatal genotoxicity and carcinogenicity of anti-retroviral nucleoside analog drugs. AN - 66792191; 15313587 AB - The current worldwide spread of the human immunodeficiency virus-1 (HIV-1) to the heterosexual population has resulted in approximately 800,000 children born yearly to HIV-1-infected mothers. In the absence of anti-retroviral intervention, about 25% of the approximately 7,000 children born yearly to HIV-1-infected women in the United States are HIV-1 infected. Administration of zidovudine (AZT) prophylaxis during pregnancy reduces the rate of infant HIV-1 infection to approximately 7%, and further reductions are achieved with the addition of lamivudine (3TC) in the clinical formulation Combivir. Whereas clinically this is a remarkable achievement, AZT and 3TC are DNA replication chain terminators known to induce various types of genotoxicity. Studies in rodents have demonstrated AZT-DNA incorporation, HPRT mutagenesis, telomere shortening, and tumorigenicity in organs of fetal mice exposed transplacentally to AZT. In monkeys, both AZT and 3TC become incorporated into the DNA from multiple fetal organs taken at birth after administration of human-equivalent protocols to pregnant dams during gestation, and telomere shortening has been found in monkey fetuses exposed to both drugs. In human infants, AZT-DNA and 3TC-DNA incorporation as well as HPRT and GPA mutagenesis have been documented in cord blood from infants exposed in utero to Combivir. In infants of mice, monkeys, and humans, levels of AZT-DNA incorporation were remarkably similar, and in newborn mice and humans, mutation frequencies were also very similar. Given the risk-benefit ratio, these highly successful drugs will continue to be used for prevention of vertical viral transmission, however evidence of genotoxicity in mouse and monkey models and in the infants themselves would suggest that exposed children should be followed well past adolescence for early detection of potential cancer hazard. JF - Toxicology and applied pharmacology AU - Poirier, Miriam C AU - Olivero, Ofelia A AU - Walker, Dale M AU - Walker, Vernon E AD - Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. poirierm@exchange.nih.gov Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 151 EP - 161 VL - 199 IS - 2 SN - 0041-008X, 0041-008X KW - Anti-HIV Agents KW - 0 KW - Carcinogens KW - Mutagens KW - Nucleosides KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - Maternal-Fetal Exchange KW - Animals, Newborn KW - Animals KW - Zidovudine -- toxicity KW - HIV Infections -- complications KW - Humans KW - Adult KW - Infant, Newborn KW - Placenta -- metabolism KW - Female KW - Pregnancy KW - Anti-HIV Agents -- toxicity KW - Nucleosides -- metabolism KW - Nucleosides -- toxicity KW - Anti-HIV Agents -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66792191?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Perinatal+genotoxicity+and+carcinogenicity+of+anti-retroviral+nucleoside+analog+drugs.&rft.au=Poirier%2C+Miriam+C%3BOlivero%2C+Ofelia+A%3BWalker%2C+Dale+M%3BWalker%2C+Vernon+E&rft.aulast=Poirier&rft.aufirst=Miriam&rft.date=2004-09-01&rft.volume=199&rft.issue=2&rft.spage=151&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 - 2004-09-20 N1 - Date created - 2004-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tobacco smoking trajectory and associated ethnic differences among adolescent smokers seeking cessation treatment. AN - 66790395; 15313503 AB - To examine smoking trajectories in a clinical sample of adolescent smokers seeking cessation treatment, including: (a) smoking onset (initial, daily) and time intervals from initial to daily smoking and from daily smoking to treatment request, (b) associations between current level of tobacco dependence and smoking history, and (c) differences in smoking trajectory between African-American and non-African-American youth. Four hundred and thirty-two adolescent smokers (aged 13-17 years, 61.8% female, 32% African-American) responding to various media advertisement completed a telephone interview as part of pre-eligibility screening for a smoking cessation trial. Smoking trajectory data included age at onset of initial and daily smoking, intervals between those time points, and cigarettes smoked per day (CPD). Tobacco dependence was assessed using the Fagerström Test for Nicotine Dependence (FTND). Data were analyzed using regression models and multiple analyses of covariance. Initial smoking occurred at a mean age of less than 12 years and daily smoking at age 13 years. Earlier onset of daily smoking was associated with higher FTND scores and longer duration from daily smoking to treatment request. For the entire sample, the time interval from initial to daily smoking was 1.14 years. When the sample was divided into early (before age 14 years) and later (at or after age 14 years) initiators, early initiators showed a slower progression from initial to daily smoking compared with late initiators (16 months vs. 6 months). Compared with non-African-American teen smokers, African-American youth reported a 1-year delay in onset of both initial and daily smoking. Early age of daily smoking and short time interval from initial to daily smoking highlight a brief window of opportunity to prevent the development of tobacco addiction and its consequences. Ethnic differences in smoking trajectory uncovered in this report call for ethnically tailored interventions to reduce youth smoking. JF - The Journal of adolescent health : official publication of the Society for Adolescent Medicine AU - Robinson, Miqun L AU - Berlin, Ivan AU - Moolchan, Eric T AD - Teen Tobacco Addiction Treatment Research Clinic, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 2004/09// PY - 2004 DA - September 2004 SP - 217 EP - 224 VL - 35 IS - 3 SN - 1054-139X, 1054-139X KW - Index Medicus KW - Regression Analysis KW - Age of Onset KW - Humans KW - European Continental Ancestry Group -- psychology KW - Interviews as Topic KW - Baltimore -- epidemiology KW - Adolescent KW - Time Factors KW - Male KW - Female KW - Patient Acceptance of Health Care -- ethnology KW - Smoking Cessation -- psychology KW - African Americans -- psychology KW - Adolescent Behavior -- psychology KW - Adolescent Behavior -- ethnology KW - Tobacco Use Disorder -- psychology KW - Tobacco Use Disorder -- ethnology KW - Smoking -- ethnology KW - Smoking -- psychology KW - Smoking Cessation -- ethnology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/66790395?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/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+adolescent+health+%3A+official+publication+of+the+Society+for+Adolescent+Medicine&rft.atitle=Tobacco+smoking+trajectory+and+associated+ethnic+differences+among+adolescent+smokers+seeking+cessation+treatment.&rft.au=Robinson%2C+Miqun+L%3BBerlin%2C+Ivan%3BMoolchan%2C+Eric+T&rft.aulast=Robinson&rft.aufirst=Miqun&rft.date=2004-09-01&rft.volume=35&rft.issue=3&rft.spage=217&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+adolescent+health+%3A+official+publication+of+the+Society+for+Adolescent+Medicine&rft.issn=1054139X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-11-26 N1 - Date created - 2004-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Predictive values of traditional animal bioassay studies for human perinatal carcinogenesis risk determination AN - 18056136; 6054515 AB - The many physiological, biochemical, and structure differences between rodents and humans, especially with regard to gestation and fetal development, invite questions as to the utility of rodent models for the prediction of risk of perinatal carcinogenesis in humans and for extrapolation of mechanistic studies. Here, the relevance of basic generalities, derived from rodent perinatal studies, to human contexts is considered. The cross-species usefulness of these generalities was upheld by the example of carcinogen activation and detoxification as determining factors. These have been established in rodent studies and recently indicted in humans by investigations of genetic polymorphisms in cytochromes P450, N-acetyltransferase, myeloperoxidase, quinone reductase, and glutathione S-transferase. Also, published data have been analyzed comparatively for diethylstilbestrol and irradiation, the two known human transplacental carcinogenic agents. At similar doses to those experienced by humans, both diethylstilbestrol and X- and gamma-irradiation in rodents and dogs yielded increased tumors at rates similar to those for humans. In rodents, there was a clearly negative relationship between total diethylstilbestrol dose and tumors per dose unit, and a similar pattern was suggested for radiation. Diethylstilbestrol had transgenerational effects that did not diminish over three generations. Overall, this analysis of the published literature indicates that there are basic qualitative and quantitative similarities in the responsiveness of human and rodent fetuses to carcinogens, and that dose effects may be complex and in need of further investigation. JF - Toxicology and Applied Pharmacology AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702, USA Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 162 EP - 174 VL - 199 IS - 2 SN - 0041-008X, 0041-008X KW - Toxicology Abstracts KW - Detoxification KW - ^g Radiation KW - quinone reductase KW - Gene polymorphism KW - Animal models KW - Carcinogens KW - Glutathione transferase KW - Myeloperoxidase KW - Fetuses KW - Gestation KW - Carcinogenesis KW - Cytochrome P450 KW - Diethylstilbestrol KW - N-Acetyltransferase KW - X 24210:Radiation & radioactive materials KW - X 24221:Toxicity testing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18056136?accountid=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=Predictive+values+of+traditional+animal+bioassay+studies+for+human+perinatal+carcinogenesis+risk+determination&rft.au=Anderson%2C+L+M&rft.aulast=Anderson&rft.aufirst=L&rft.date=2004-09-01&rft.volume=199&rft.issue=2&rft.spage=162&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1016%2Fj.taap.2004.02.008 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Diethylstilbestrol; Carcinogenesis; Carcinogens; Fetuses; quinone reductase; Glutathione transferase; Myeloperoxidase; Cytochrome P450; Detoxification; N-Acetyltransferase; ^g Radiation; Gene polymorphism; Gestation; Animal models DO - http://dx.doi.org/10.1016/j.taap.2004.02.008 ER - TY - JOUR T1 - Lessons learned from perinatal exposure to diethylstilbestrol AN - 18053512; 6054521 AB - The synthetic estrogen diethylstilbestrol (DES) is well documented to be a perinatal carcinogen in both humans and experimental animals. Exposure to DES during critical periods of differentiation permanently alters the programming of estrogen target tissues resulting in benign and malignant abnormalities in the reproductive tract later in life. Using the perinatal DES-exposed rodent model, cellular and molecular mechanisms have been identified that play a role in these carcinogenic effects. Although DES is a potent estrogenic chemical, effects of low doses of the compound are being used to predict health risks of weaker environmental estrogens. Therefore, it is of particular interest that developmental exposure to very low doses of DES has been found to adversely affect fertility and to increase tumor incidence in murine reproductive tract tissues. These adverse effects are seen at environmentally relevant estrogen dose levels. New studies from our lab verify that DES effects are not unique; when numerous environmental chemicals with weak estrogenic activity are tested in the experimental neonatal mouse model, developmental exposure results in an increased incidence of benign and malignant tumors including uterine leiomyomas and adenocarcinomas that are similar to those shown following DES exposure. Finally, growing evidence in experimental animals suggests that some adverse effects can be passed on to subsequent generations, although the mechanisms involved in these trans-generational events remain unknown. Although the complete spectrum of risks to DES-exposed humans are uncertain at this time, the scientific community continues to learn more about cellular and molecular mechanisms by which perinatal carcinogenesis occurs. These advances in knowledge of both genetic and epigenetic mechanisms will be significant in ultimately predicting risks to other environmental estrogens and understanding more about the role of estrogens in normal and abnormal development. JF - Toxicology and Applied Pharmacology AU - Newbold, R R AD - Developmental Endocrinology Section, Laboratory of Toxicology, Environmental Toxicology Program, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 2004/09/01/ PY - 2004 DA - 2004 Sep 01 SP - 142 EP - 150 VL - 199 IS - 2 SN - 0041-008X, 0041-008X KW - Toxicology Abstracts KW - Fertility KW - Estrogens KW - Animal models KW - Carcinogens KW - estrogenic activity KW - Differentiation KW - Perinatal exposure KW - epigenetics KW - Carcinogenesis KW - Neonates KW - Adenocarcinoma KW - Diethylstilbestrol KW - Side effects KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18053512?accountid=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=Lessons+learned+from+perinatal+exposure+to+diethylstilbestrol&rft.au=Newbold%2C+R+R&rft.aulast=Newbold&rft.aufirst=R&rft.date=2004-09-01&rft.volume=199&rft.issue=2&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1016%2Fj.taap.2003.11.033 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Estrogens; Side effects; Animal models; Diethylstilbestrol; Fertility; Perinatal exposure; Neonates; epigenetics; Carcinogenesis; Carcinogens; Differentiation; estrogenic activity; Adenocarcinoma DO - http://dx.doi.org/10.1016/j.taap.2003.11.033 ER - TY - JOUR T1 - Bis(2-chloroethoxy)methane-Induced Mitochondrial and Myofibrillar Damage: Short-Term Time-Course Study AN - 18028220; 5992154 AB - Cardiotoxicity induced by 2-, 3-, 5-, and 12-day dermal administration of 400 and 600 mg/kg/day of bis(2-chloroethoxy)methane to F344/N male and female rats was characterized. The severity and incidence of lesions were similar among males and females and in all three regions of the heart examined (atrium, ventricle, interventricular septum). Damage induced by bis(2- chloroethoxy)methane consisted of time-related development of myofiber vacuolation, necrosis, mononuclear-cell infiltration, fibrosis, and atrial thrombosis. Changes were pronounced at day 2, increased in severity at day 3, appeared to decrease at day 5, and resolved by study-day 16 that corresponded to 12 dosings. Ultrastructural analysis of 2- and 5-day 600 mg/kg/day-treated females elucidated the primary site of damage, the mitochondrion, and two types of vacuolation, one that formed as damaged mitochondria became devoid of cristae and their bounding double membranes became reduced to singleness, and the other manifested as distention of the sarcoplasmic reticulum. After the initial damage induced by bis(2-chloroethoxy)methane, or its metabolite, thiodiglycolic acid, protective mechanisms within the heart were apparently initiated, enabling it to cope with the continued exposure to the toxicant while eliminating some damaged myofibers. JF - Toxicological Sciences AU - Dunnick, June AU - Johnson, Joanne AU - Horton, John AU - Nyska, Abraham AD - Environmental Toxicology Program, and Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 243 EP - 252 PB - Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, [mailto:jnl.samples@oup.co.uk], [URL:http://www3.oup.co.uk/jnls/] VL - 81 IS - 1 SN - 1096-6080, 1096-6080 KW - bis(2-chloroethoxy)methane KW - rats KW - Toxicology Abstracts KW - Sarcoplasmic reticulum KW - Necrosis KW - Fibrosis KW - thiodiglycolic acid KW - Infiltration KW - Mitochondria KW - Lesions KW - Metabolites KW - Thrombosis KW - Myofibrils KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18028220?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Bis%282-chloroethoxy%29methane-Induced+Mitochondrial+and+Myofibrillar+Damage%3A+Short-Term+Time-Course+Study&rft.au=Dunnick%2C+June%3BJohnson%2C+Joanne%3BHorton%2C+John%3BNyska%2C+Abraham&rft.aulast=Dunnick&rft.aufirst=June&rft.date=2004-09-01&rft.volume=81&rft.issue=1&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Sarcoplasmic reticulum; Necrosis; Fibrosis; Infiltration; thiodiglycolic acid; Lesions; Mitochondria; Metabolites; Thrombosis; Myofibrils ER - TY - JOUR T1 - Crystal Structure of A. fulgidus Rio2 Defines a New Family of Serine Protein Kinases AN - 17796323; 6004950 AB - The RIO family of atypical serine/threonine kinases contains two subfamilies, Rio1 and Rio2, highly conserved from archaea to man. Both RIO proteins from Saccharomyces cerevisiae catalyze serine phosphorylation in vitro, and the presence of conserved catalytic residues is required for cell viability. The activity of Rio2 is necessary for rRNA cleavage in 40S ribosomal subunit maturation. We solved the X-ray crystal structure of Archaeoglobus fulgidus Rio2, with and without bound nucleotides, at 2.0 Aa resolution. The C- terminal RIO domain is indeed structurally homologous to protein kinases, although it differs from known serine kinases in ATP binding and lacks the regions important for substrate binding. Unexpectedly, the N-terminal Rio2- specific domain contains a winged helix fold, seen primarily in DNA-binding proteins. These discoveries have implications in determining the target and function of RIO proteins and define a distinct new family of protein kinases. JF - Structure AU - LaRonde-LeBlanc, N AU - Wlodawer, A AD - Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute, NCI-Frederick, Frederick, MD 21702, USA, wlodawer@ncifcrf.gov Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 1585 EP - 1594 PB - Cell Press, 1100 Massachusetts Avenue Cambridge MA 02138 USA, [mailto:subs@cell.com], [URL:http://www.cellpress.com] VL - 12 IS - 9 SN - 0969-2126, 0969-2126 KW - Rio2 protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Archaea KW - Protein-serine/threonine kinase KW - RNA-binding protein KW - Archaeoglobus fulgidus KW - ATP KW - Ribosomal subunits KW - Nucleotides KW - Saccharomyces cerevisiae KW - rRNA KW - Phosphorylation KW - Crystal structure KW - Protein kinase KW - Serine KW - J 02728:Enzymes KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17796323?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Structure&rft.atitle=Crystal+Structure+of+A.+fulgidus+Rio2+Defines+a+New+Family+of+Serine+Protein+Kinases&rft.au=LaRonde-LeBlanc%2C+N%3BWlodawer%2C+A&rft.aulast=LaRonde-LeBlanc&rft.aufirst=N&rft.date=2004-09-01&rft.volume=12&rft.issue=9&rft.spage=1585&rft.isbn=&rft.btitle=&rft.title=Structure&rft.issn=09692126&rft_id=info:doi/10.1016%2Fj.str.2004.06.016 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - rRNA; Phosphorylation; RNA-binding protein; Protein-serine/threonine kinase; Crystal structure; ATP; Protein kinase; Ribosomal subunits; Nucleotides; Serine; Archaea; Archaeoglobus fulgidus; Saccharomyces cerevisiae DO - http://dx.doi.org/10.1016/j.str.2004.06.016 ER - TY - JOUR T1 - Research Opportunities on Human Neuroborreliosis AN - 17641777; 6417965 AB - A workshop, sponsored by the National Institutes of Health, was convened in September 2001 to evaluate the current knowledge in neurological Lyme disease. The meeting was centered into discussion of both clinical and basic aspects of the disease. Participants included researchers from the fields of infectious diseases, neurology, rheumatology, autoimmunity and basic immunology, largely but not exclusively focused on Lyme disease. This report summarizes the presentations made at the meeting. JF - Vector Borne and Zoonotic Diseases AU - Gelderblom, H AU - Martin, R AU - Marques, A R AD - Cellular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 261 EP - 272 VL - 4 IS - 3 SN - 1530-3667, 1530-3667 KW - neuroborreliosis KW - Microbiology Abstracts B: Bacteriology KW - J 02848:Nervous system UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17641777?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vector+Borne+and+Zoonotic+Diseases&rft.atitle=Research+Opportunities+on+Human+Neuroborreliosis&rft.au=Gelderblom%2C+H%3BMartin%2C+R%3BMarques%2C+A+R&rft.aulast=Gelderblom&rft.aufirst=H&rft.date=2004-09-01&rft.volume=4&rft.issue=3&rft.spage=261&rft.isbn=&rft.btitle=&rft.title=Vector+Borne+and+Zoonotic+Diseases&rft.issn=15303667&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2005-09-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Live vaccinia-rabies virus recombinants, but not an inactivated rabies virus cell culture vaccine, protect B-lymphocyte-deficient A/WySnJ mice against rabies: considerations of recombinant defective poxviruses for rabies immunization of immunocompromised individuals AN - 1500773671; 19046260 AB - Presently, commercially available cell culture rabies vaccines for humans and animals consist of the five inactivated rabies virus proteins. The vaccines elicit a CD4+ helper T-cell response and a humoral B-cell response against the viral glycoprotein (G) resulting in the production of virus neutralizing antibody. Antibody against the viral nucleoprotein (N) is also present, but the mechanism(s) of its protection is unclear. HIV-infected individuals with low CD4+ T-lymphocyte counts and individuals undergoing treatment with immunosuppressive drugs have an impaired neutralizing antibody response after pre- and post-exposure immunization with rabies cell culture vaccines. Here we show the efficacy of live vaccinia-rabies virus recombinants, but not a cell culture vaccine consisting of inactivated rabies virus, to elicit elevated levels of neutralizing antibody in B-lymphocyte deficient A/WySnJ mice. The cell culture vaccine also failed to protect the mice, whereas a single immunization of a vaccinia recombinant expressing the rabies virus G or co-expressing G and N equally protected the mice up to 18 months after vaccination. The data suggest that recombinant poxviruses expressing the rabies virus G, in particular replication defective poxviruses such as canarypox or MVA vaccinia virus that undergo abortive replication in non-avian cells, or the attenuated vaccinia virus NYVAC, should be evaluated as rabies vaccines in immunocompromised individuals. JF - Vaccine AU - Lodmell, Donald L AU - Esposito, Joseph J AU - Ewalt, Larry C AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA Y1 - 2004/09// PY - 2004 DA - Sep 2004 SP - 3329 EP - 3333 PB - Elsevier B.V., The Boulevard Kidlington Oxford OX5 1GB United Kingdom VL - 22 IS - 25 SN - 0264-410X, 0264-410X KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - glycoprotein G KW - Data processing KW - Vaccinia KW - Lymphocytes B KW - Replication KW - Nucleoproteins KW - Cell culture KW - Antibody response KW - Immunosuppressive agents KW - Recombinants KW - CD4 antigen KW - Vaccinia virus KW - Human immunodeficiency virus KW - Rabies KW - Lymphocytes T KW - Rabies virus KW - Vaccines KW - V 22360:AIDS and HIV KW - F 06905:Vaccines KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1500773671?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info: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=Live+vaccinia-rabies+virus+recombinants%2C+but+not+an+inactivated+rabies+virus+cell+culture+vaccine%2C+protect+B-lymphocyte-deficient+A%2FWySnJ+mice+against+rabies%3A+considerations+of+recombinant+defective+poxviruses+for+rabies+immunization+of+immunocompromised+individuals&rft.au=Lodmell%2C+Donald+L%3BEsposito%2C+Joseph+J%3BEwalt%2C+Larry+C&rft.aulast=Lodmell&rft.aufirst=Donald&rft.date=2004-09-01&rft.volume=22&rft.issue=25&rft.spage=3329&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/10.1016%2Fj.vaccine.2004.02.039 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2014-02-01 N1 - Last updated - 2014-06-12 N1 - SubjectsTermNotLitGenreText - glycoprotein G; Data processing; Replication; Lymphocytes B; Vaccinia; Nucleoproteins; Cell culture; Antibody response; Immunosuppressive agents; Recombinants; CD4 antigen; Rabies; Lymphocytes T; Vaccines; Vaccinia virus; Human immunodeficiency virus; Rabies virus DO - http://dx.doi.org/10.1016/j.vaccine.2004.02.039 ER -