FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Piknova, B Keszler, A Hogg, N Schechter, AN AF Piknova, Barbara Keszler, Agnes Hogg, Neil Schechter, Alan N. TI A model to describe the reaction of oxyhemoglobin solutions with nitrite ions SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 5th International Conference on Biology, Chemistry, and Therapeutic Applications of Nitric Oxide CY AUG 24-28, 2008 CL Bregenz, AUSTRIA C1 [Piknova, Barbara; Schechter, Alan N.] NIDDK, MMB, NIH, Bethesda, MD 20892 USA. [Keszler, Agnes; Hogg, Neil] Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2008 VL 19 SU S BP S51 EP S51 DI 10.1016/j.niox.2008.06.132 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 334WY UT WOS:000258253500130 ER PT J AU Raat, NJ Noguchi, AC Liu, V Raghavachari, N Liu, DL Xu, XL Shiva, S Munson, PM Gladwin, MT AF Raat, Nicolaas J. Noguchi, Audrey C. Liu, Virginia Raghavachari, Nalini Liu, Delong Xu, Xiuli Shiva, Sruti Munson, Peter M. Gladwin, Mark T. TI Dietary nitrate and nitrite modulate the cellular response to ischemic stress SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 5th International Conference on Biology, Chemistry, and Therapeutic Applications of Nitric Oxide CY AUG 24-28, 2008 CL Bregenz, AUSTRIA C1 [Raat, Nicolaas J.; Noguchi, Audrey C.; Liu, Virginia; Raghavachari, Nalini; Xu, Xiuli; Shiva, Sruti; Gladwin, Mark T.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Liu, Delong; Munson, Peter M.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. [Gladwin, Mark T.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2008 VL 19 SU S BP S55 EP S55 DI 10.1016/j.niox.2008.06.149 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 334WY UT WOS:000258253500146 ER PT J AU Rassaf, T Hendgen-Cotta, U Merx, M Schmitz, J Shiva, S Klare, J Goedecke, A Schrader, J Gladwin, MT Kelm, M AF Rassaf, Tienush Hendgen-Cotta, Ulrike Merx, Marc Schmitz, Joel Shiva, Sruti Klare, Johann Goedecke, Axel Schrader, Juergen Gladwin, Mark T. Kelm, Malte TI Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 5th International Conference on Biology, Chemistry, and Therapeutic Applications of Nitric Oxide CY AUG 24-28, 2008 CL Bregenz, AUSTRIA C1 [Rassaf, Tienush; Hendgen-Cotta, Ulrike; Merx, Marc; Schmitz, Joel; Kelm, Malte] Univ Hosp Aachen, Dept Cardiol, Aachen, Germany. [Shiva, Sruti; Gladwin, Mark T.] NIH, Bethesda, MD 20892 USA. [Klare, Johann] Univ Osnabruck, D-4500 Osnabruck, Germany. [Goedecke, Axel; Schrader, Juergen] Univ Duesseldorf, Dusseldorf, Germany. RI Klare, Johann/C-1428-2009 OI Klare, Johann/0000-0002-5761-5968 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2008 VL 19 SU S BP S52 EP S52 DI 10.1016/j.niox.2008.06.138 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 334WY UT WOS:000258253500135 ER PT J AU Rizzatti, FG Qasi, M Stroncek, D Sibmooh, N Piknova, B Schechter, AN AF Rizzatti, Fabiola G. Qasi, Melissa Stroncek, David Sibmooh, Nathawut Piknova, Barbara Schechter, Alan N. TI Retention of nitric oxide metabolites by stored human erythrocytes SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 5th International Conference on Biology, Chemistry, and Therapeutic Applications of Nitric Oxide CY AUG 24-28, 2008 CL Bregenz, AUSTRIA C1 [Rizzatti, Fabiola G.; Qasi, Melissa; Sibmooh, Nathawut; Piknova, Barbara; Schechter, Alan N.] NIDDK, NIH, Bethesda, MD 20892 USA. [Stroncek, David] NIH, Div Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2008 VL 19 SU S BP S54 EP S54 DI 10.1016/j.niox.2008.06.147 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 334WY UT WOS:000258253500144 ER PT J AU Shiva, S Gladwin, MT AF Shiva, Sruti Gladwin, Mark T. TI Nitrite mediates cytoprotection after ischernia/reperfusion through the modulation of mitochondrial function SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 5th International Conference on Biology, Chemistry, and Therapeutic Applications of Nitric Oxide CY AUG 24-28, 2008 CL Bregenz, AUSTRIA C1 [Shiva, Sruti; Gladwin, Mark T.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2008 VL 19 SU S BP S28 EP S28 DI 10.1016/i.niox.2008.06.035 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 334WY UT WOS:000258253500035 ER PT J AU Tiso, M Wang, X Shiva, S Mendelsohn, L Gladwin, MT AF Tiso, Mauro Wang, Xunde Shiva, Stud Mendelsohn, Laurel Gladwin, Mark T. TI Human neuroglobin functions as an allosteric nitrite reductase in hypoxia SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 5th International Conference on Biology, Chemistry, and Therapeutic Applications of Nitric Oxide CY AUG 24-28, 2008 CL Bregenz, AUSTRIA C1 [Tiso, Mauro; Wang, Xunde; Shiva, Stud; Mendelsohn, Laurel; Gladwin, Mark T.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2008 VL 19 SU S BP S28 EP S28 DI 10.1016/j.niox.2008.06.037 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 334WY UT WOS:000258253500037 ER PT J AU Wood, KC Liu, VB Gladwin, MT AF Wood, Katherine C. Liu, Virginia B. Gladwin, Mark T. TI Anesthetic modulation of physiological nitric oxide species SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 5th International Conference on Biology, Chemistry, and Therapeutic Applications of Nitric Oxide CY AUG 24-28, 2008 CL Bregenz, AUSTRIA C1 [Wood, Katherine C.; Liu, Virginia B.; Gladwin, Mark T.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Gladwin, Mark T.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PY 2008 VL 19 SU S BP S53 EP S54 DI 10.1016/j.niox.2008.06.144 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 334WY UT WOS:000258253500141 ER PT S AU Basu, S Wang, XD Gladwin, MT Kim-Shapiro, DB AF Basu, Swati Wang, Xunde Gladwin, Mark T. Kim-Shapiro, Daniel B. BE Cadenas, E Packer, L TI Chemiluminescent detection of S-nitrosated proteins: Comparison of tri-iodide, copper/CO/cysteine, and modified copper/cysteine methods SO NITRIC OXIDE, PART F: OXIDATIVE AND NITROSATIVE STRESS IN REDOX REGULATION OF CELL SIGNALING SE Methods in Enzymology LA English DT Review; Book Chapter ID RED-BLOOD-CELL; NITRIC-OXIDE; IN-VIVO; CIRCULATING NITRITE; GLYCERYL TRINITRATE; BIOLOGICAL-SYSTEMS; SERUM-ALBUMIN; NITROSOTHIOLS; NO; NITROSYLATION AB The precise quantification of high and low molecular weight S-nitrosothiols (RSNOs) in biological samples is necessary for the study of nitric oxide-dependent posttranslational signal transduction. Several chemiluminescence-based methods are used for the detection of S-nitrosothiols using the nitric oxide analyzer, including the tri-iodide method and the Cu/CO/cysteine (3C) method. Despite the fact that the tri-idodide method is the most widely used and validated methodology, the levels of S-nitrosated hemoglobin (SNO-Hb) and S-nitrosated albumin have been lower than those reported using photolysis coupled to chemiluminescence. This chapter demonstrates that the tri-iodide method and a newly developed modified copper/cysteine (2C) method compare favorably with the 3C method. Our comparisons include physiologically relevant conditions where the ratio of SNO to heme is low and the frequency of nitrosation of a given Hb tetramer is less than 1. In our studies, the tri-iodide method, the 3C method, and the modified 2C method give consistent and reproducible results. These studies suggest that the proper use of any of these methods can be effective in the accurate measurement of S-nitrosothiols in biological samples. Using more than one in combination has the potential to resolve controversies related to the role of hemoglobin in the generation of RSNOs or the role of RSNOs in biology, whether the RSNOs derive from nitrite or other nitrosative pathways. C1 [Basu, Swati; Kim-Shapiro, Daniel B.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. [Wang, Xunde; Gladwin, Mark T.] NHLBI, Pulm & Vasc Med Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Gladwin, Mark T.] Natl Inst Hlth, Dept Crit Care Med, Ctr Clin, Bethesda, MD USA. RP Basu, S (reprint author), Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. NR 55 TC 19 Z9 19 U1 0 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-373967-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 440 BP 137 EP 156 DI 10.1016/S0076-6879(07)00808-7 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BHR79 UT WOS:000255834700008 PM 18423215 ER PT B AU Bumb, A Dobson, PJ Fugger, L Choyke, P Brechbiel, MW AF Bumb, A. Dobson, P. J. Fugger, L. Choyke, P. Brechbiel, M. W. BE Laudon, M Romanowicz, B TI Nanomedicine: Engineering of a Tri-Imageable Nanoparticle for Cancer Diagnostics SO NSTI NANOTECH 2008, VOL 2, TECHNICAL PROCEEDINGS: LIFE SCIENCES, MEDICINE, AND BIO MATERIALS LA English DT Proceedings Paper CT Nanotechnology Conference and Trade Show (Nanotech 2008) CY JUN 01-05, 2008 CL Boston, MA SP Accelrys Software, Ace Glass, Advance Reprod Corp, Adv Mat Technolog Pte Ltd, Agilent Technol, AIXTRON AG, AJA Int, ALM, Amuneal Mfg Corp, ANSYS, Anton Paar, Appl MicroStruct, Appl Surface Technol, Arkalon Chem Technolog, LLC, Arkema Grp, Artech House Publishers, Asemblon, ASML, Asylum Res, AZoNano, Banner & Witcoff, Beckman Coulter, Bio Nano Counsulting, BioForce Nanosci, Boneer Corp, Birck Nanotechnol Ctr, Purdue Univ, Discovery Pk, Brookhaven Instruments Corp, Buchanan Ingersoll & Rooney PC, Buhler AG, Business Week, Calif NanoSyst Inst, Capovani Brothers, Los Alamos, Ctr Integrated Nanotechnologies, Sandia Natl Labs, Ctr Integrated Nanotechnologies, Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Argonne Natl Lab, Ctr Nanoscale Mat, Cheap tubes, Clean Technol & Sustainable Ind Org, COMSOL, Cooley Godward Kronish LLP, Core Technol Grp, CRESTEC Corp, CSEM, CVI Melles Griot, Dept Innovat, Ind, Sci & Res, Digital Matrix, Draiswerke, ETH Zurich, Eulitha AG, Marks & Clerk, Marubent Techno Syst Corp, Massachusetts Technol Transfer Ctr, Mat Res Soc, Merck & Co, Microfluidics, Micromerit Instrument Corp, Microtrac, MINAT 2008, Messe Stuttgart, Minus K Technol, Misonix, Lawrence Berkeley Natl Lab, Mol Foundry, Motorola, Nano Korea 2008, Nano Sci & Technol Inst, nano tech 2009 Japan, Nano Technol Res Assoc Korea, NanoAndMore USA, NanoDynamics, NanoEurope 2008, NanoInk, Nanomotion, Nanon Imaging Ltd, NANOSENSORS, Nanosyst Initiat Munich, Nanotech No Europe 2008, nano Tox, Nano World AG, NCI, Natl Inst Stand & Technol, NIH, Natl Nanomfg Network, Natl Nanotechnol Infrastruct, GATech, Microelect Res Ctr, Nat Nano, Nat Publishing Grp, NETZSCH Fine Particle Technol LLC, NIL Technol ApS, Novomer, NTT Adv Technol Corp, Olympus Ind Amer, OSEC, Business Network Switzerland, Oxford Instruments, Particle Technol Labs, Penn State Univ, Photon Spectra, Physik Instrumente LP, picoDrill SA, Piezo Inst, PVD Prod, Q Sense, Quantum Analyt, Raith USA, European Patent Off, Evans Analyt Grp, EXAKT Technologies, First Nano, Flow Sci, FDA, Goodwin Procter LLP, Greater Houston Partnership, Greenberg Traurig LLP, Halcyonics, Headwaters Technol Innovat LLC, Heidelberg Instruments, Hielscher USA, HighNano Analyti, Hiscock & Barclay LLP, Hitachi High Technologies Amer, Hochschule Offenburg Univ Appl Sci, HOCKMEYER Equipment Corp, HORIBA Jobin Yvon, IBU-tec adv mat GmbH, IDA Ireland, ImageXpert, Inspec, Inc, IEEE, Inst Nanoscale & Quantum Sci & Technol Adv Res, IntelliSense Software Corp, Invest Germany, IOP Publishing, Italian Trade Commiss, JENOPTIK, Justus Liebig Univ, KAUST, Keithley Instruments, Kelvin Nanotechnol Ltd, Kodak, Kotobuki Ind Co, Ltd, Lake Shore Cryotron, MACRO M, NanoClay, Res Germany Land Ideas, RKS Legal Solut LLC, Dandia Natl Labs, Scottish Enterprise, SEMTech Solut, Serendip, Silvix Corp, SNS Nano Fiber Technol LLC, SoftMEMS LLC, Son & Mat, SW Nano Technologies, Specialty Coating Syst, Spectrum Labs, SPEX SamplePrep LLC, Springer, Sterne, Kessler, Goldstein & Fox PLLC, Strem Chem, Sukgyung A T Co, Lts, Surrey NanoSyst, SUSS MicroTec, Swissnanotech Pavilion, Taylor & Francis Grp LLC, CRC Press, TechConnect, Technovel Corp, Tekna Plasma Syst, Thinky Corp, Thomas Swan & Co Ltd, UGL Unicco, UK Trade & Investment, UniJet, Univ Munster, Univ Appl Sci, Univ Duisburg, Ctr Nanointegrat Duisburg, Vecco Instruments, Wasatch Mol Inc, Weidmann Plast Technol, Whiteman Osterman & Hanna LLP, Willy A Bachofen AG, WITec GmbH, World Gold Council DE Cancer Diagnostics; Imaging; Nanoparticle; Tri-Imaging ID ANTIBODY; RADIOIMMUNOTHERAPY; ENCAPSULATION; RECEPTOR; ANTIGEN; GROWTH; AGENT AB We have created a potential targeted drug delivery platform with three imaging reporters by coupling the magnetic properties of USPIOs with near infrared fluorescence of Cy5.5 and gamma-emissions of In-111 that is chelated to a conjugated antibody. The nanoparticle will allow for not only triple verification of localization, but also quantification. During each phase of development, the nanoparticles have been characterized for surface charge and structure by transmission electron microscopy and dynamic light scattering. Magnetic properties including hysteresis measurements and field cooling analyses were conducted using a superconducting quantum interference device. In vitro analyses of flow cytometry and cell viability as well as in vivo imaging studies have been conducted. C1 [Bumb, A.; Choyke, P.; Brechbiel, M. W.] Natl Canc Inst, Bethesda, MD 20892 USA. [Dobson, P. J.; Fugger, L.] Univ Oxford, Oxford OX1 2JD, England. RP Bumb, A (reprint author), Natl Canc Inst, Bethesda, MD 20892 USA. EM bumba@mail.nih.gov; peter.dobson@eng.ox.ac.uk; lars.fugger@imm.ox.ac.uk; pchoyke@mail.nih.gov; martinwb@mail.nih.gov NR 17 TC 0 Z9 0 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4200-8504-4 PY 2008 BP 1 EP + PG 2 WC Nanoscience & Nanotechnology; Medicine, General & Internal; Medicine, Research & Experimental; Materials Science, Biomaterials SC Science & Technology - Other Topics; General & Internal Medicine; Research & Experimental Medicine; Materials Science GA BMF49 UT WOS:000272169900001 ER PT J AU Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Wheeler, DL AF Benson, Dennis A. Karsch-Mizrachi, Ilene Lipman, David J. Ostell, James Wheeler, David L. TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE AB GenBank (R) is a comprehensive database that contains publicly available nucleotide sequences for more than 260 000 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 European Molecular Biology Laboratory Nucleotide Sequence Database in Europe and the DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through NCBIs 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, begin at the NCBI Homepage: www.ncbi.nlm.nih.gov. C1 [Benson, Dennis A.; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Wheeler, David L.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wheeler, DL (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM wheeler@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 12 TC 574 Z9 592 U1 2 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2008 VL 36 SI SI BP D25 EP D30 DI 10.1093/nar/gkm929 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253VJ UT WOS:000252545400006 PM 18073190 ER PT J AU Bindewald, E Hayes, R Yingling, YG Kasprzak, W Shapiro, BA AF Bindewald, Eckart Hayes, Robert Yingling, Yaroslava G. Kasprzak, Wojciech Shapiro, Bruce A. TI RNAJunction: a database of RNA junctions and kissing loops for three-dimensional structural analysis and nanodesign SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEIC-ACIDS; BUILDING-BLOCKS; CLASSIFICATION; SCOR; DNA; VERSION-2.0; DESIGN; MOTIFS AB We developed a database called RNAJunction that contains structure and sequence information for RNA structural elements such as helical junctions, internal loops, bulges and loop-loop interactions. Our database provides a user- friendly way of searching structural elements by PDB code, structural classification, sequence, keyword or inter-helix angles. In addition, the structural data was subjected to energy minimization. This database is useful for analyzing RNA structures as well as for designing novel RNA structures on a nanoscale. The database can be accessed at: http://rnajunction.abcc.ncifcrf.gov/. C1 [Hayes, Robert; Yingling, Yaroslava G.; Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Bindewald, Eckart; Kasprzak, Wojciech] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM bshapiro@ncifcrf.gov RI Yingling, Yaroslava/B-2901-2008 OI Yingling, Yaroslava/0000-0002-8557-9992 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO-12400] NR 28 TC 78 Z9 79 U1 3 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2008 VL 36 SI SI BP D392 EP D397 DI 10.1093/nar/gkm842 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253VJ UT WOS:000252545400071 PM 17947325 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI The molecular biology database collection: 2008 update SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RESOURCE; MOUSE AB The Nucleic Acids Research online Molecular Biology Database Collection is a public repository that lists more than 1000 databases described in this and previous Nucleic Acids Research annual database issues, as well as a selection of molecular biology databases described in other journals. All databases included in this Collection are freely available to the public. The 2008 update includes 1078 databases, 110 more than the previous one. The links to more than 80 databases have been updated and 25 obsolete databases have been removed from the list. The complete database list and summaries are available online at the Nucleic Acids Research web site, http://nar.oxfordjournals.org/. C1 Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS [Z99 LM999999] NR 25 TC 57 Z9 62 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2008 VL 36 SI SI BP D2 EP D4 DI 10.1093/nar/gkm1037 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253VJ UT WOS:000252545400002 PM 18025043 ER PT J AU Pugalenthi, G Suganthan, PN Sowdhamini, R Chakrabarti, S AF Pugalenthi, Ganesan Suganthan, P. N. Sowdhamini, R. Chakrabarti, Saikat TI MegaMotifBase: a database of structural motifs in protein families and superfamilies SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SEQUENCE; ALIGNMENTS AB Structural motifs are important for the integrity of a protein fold and can be employed to design and rationalize protein engineering and folding experiments. Such conserved segments represent the conserved core of a family or superfamily and can be crucial for the recognition of potential new members in sequence and structure databases. We present a database, MegaMotifBase, that compiles a set of important structural segments or motifs for protein structures. Motifs are recognized on the basis of both sequence conservation and preservation of important structural features such as amino acid preference, solvent accessibility, secondary structural content, hydrogen-bonding pattern and residue packing. This database provides 3D orientation patterns of the identified motifs in terms of inter-motif distances and torsion angles. Important applications of structural motifs are also provided in several crucial areas such as similar sequence and structure search, multiple sequence alignment and homology modeling. MegaMotifBase can be a useful resource to gain knowledge about structure and functional relationship of proteins. The database can be accessed from the URL http://caps.ncbs.res.in/MegaMotifbase/index.html. C1 [Sowdhamini, R.] Natl Ctr Biol Sci, Bangalore 560065, Karnataka, India. [Pugalenthi, Ganesan; Suganthan, P. N.] Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore. [Chakrabarti, Saikat] Natl Lib Med, NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Sowdhamini, R (reprint author), Natl Ctr Biol Sci, UAS-GKVK Campus,Bellary Rd, Bangalore 560065, Karnataka, India. EM mini@ncbs.res.in; chakraba@mail.nlm.nih.gov RI Suganthan, .Ponnuthurai /A-5023-2011 OI Suganthan, .Ponnuthurai /0000-0003-0901-5105 FU Intramural NIH HHS; Wellcome Trust NR 16 TC 15 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2008 VL 36 SI SI BP D218 EP D221 DI 10.1093/nar/gkm794 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253VJ UT WOS:000252545400040 PM 17933773 ER PT J AU Raghavachari, B Tasneem, A Przytycka, TM Jothi, R AF Raghavachari, Balaji Tasneem, Asba Przytycka, Teresa M. Jothi, Raja TI DOMINE: a database of protein domain interactions SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; INTERACTION MAP; COMPLEXES; PREDICTION; NETWORK AB DOMINE is a database of known and predicted protein domain interactions compiled from a variety of sources. The database contains domaindomain interactions observed in PDB entries, and those that were predicted by eight different computational approaches. DOMINE contains a total of 20 513 unique domaindomain interactions among 4036 Pfam domains, out of which 4349 are inferred from PDB entries and 17 781 were predicted by at least one computational approach. This database will serve as a valuable resource to those working in the field of protein and domain interactions. DOMINE may not only serve as a reference to experimentalists who test for new protein and domain interactions, but also offers a consolidated dataset for analysis by bioinformaticians who seek to test ideas regarding the underlying factors that control the topological structure of interaction networks. DOMINE is freely available at http://domine.utdallas.edu. C1 [Raghavachari, Balaji] Univ Texas Dallas, Dept Comp Sci, Richardson, TX 75083 USA. [Przytycka, Teresa M.; Jothi, Raja] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Jothi, R (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM jothi@mail.nih.gov RI Jothi, Raja/G-3780-2015 FU Intramural NIH HHS NR 29 TC 69 Z9 73 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2008 VL 36 SI SI BP D656 EP D661 DI 10.1093/nar/gkm761 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253VJ UT WOS:000252545400118 PM 17913741 ER PT J AU Tanaka, T Antonio, BA Kikuchi, S Matsumoto, T Nagamura, Y Numa, H Sakai, H Wu, J Itoh, T Sasaki, T Aono, R Fujii, Y Habara, T Harada, E Kanno, M Kawahara, Y Kawashima, H Kubooka, H Matsuya, A Nakaoka, H Saichi, N Sanbonmatsu, R Sato, Y Shinso, Y Suzuki, M Takeda, JI Tanino, M Todokoro, F Yamaguchi, K Yamamoto, N Yamasaki, C Imanishi, T Okido, T Tada, M Ikeo, K Tateno, Y Gojobori, T Lin, YC Wei, FJ Hsing, YI Zhao, Q Han, B Kramer, MR McCombie, RW Lonsdale, D O'Donovan, CC Whitfield, EJ Apweiler, R Koyanagi, KO Khurana, JP Raghuvanshi, S Singh, NK Tyagi, AK Haberer, G Fujisawa, M Hosokawa, S Ito, Y Ikawa, H Shibata, M Yamamoto, M Bruskiewich, RM Hoen, DR Bureau, TE Namiki, N Ohyanagi, H Sakai, Y Nobushima, S Sakata, K Barrero, RA Sato, Y Souvorov, A Smith-White, B Tatusova, T An, S An, G OOta, S Fuks, G Messing, J Christie, KR Lieberherr, D Kim, H Zuccolo, A Wing, RA Nobuta, K Green, PJ Lu, C Meyers, BC Chaparro, C Piegu, B Panaud, O Echeverria, M AF Tanaka, Tsuyoshi Antonio, Baltazar A. Kikuchi, Shoshi Matsumoto, Takashi Nagamura, Yoshiaki Numa, Hisataka Sakai, Hiroaki Wu, Jianzhong Itoh, Takeshi Sasaki, Takuji Aono, Ryo Fujii, Yasuyuki Habara, Takuya Harada, Erimi Kanno, Masako Kawahara, Yoshihiro Kawashima, Hiroaki Kubooka, Hiromi Matsuya, Akihiro Nakaoka, Hajime Saichi, Naomi Sanbonmatsu, Ryoko Sato, Yoshiharu Shinso, Yuji Suzuki, Mami Takeda, Jun-Ichi Tanino, Motohiko Todokoro, Fusano Yamaguchi, Kaori Yamamoto, Naoyuki Yamasaki, Chisato Imanishi, Tadashi Okido, Toshihisa Tada, Masahito Ikeo, Kazuho Tateno, Yoshio Gojobori, Takashi Lin, Yao-Cheng Wei, Fu-Jin Hsing, Yue-Ie Zhao, Qiang Han, Bin Kramer, Melissa R. McCombie, Richard W. Lonsdale, David O'Donovan, Claire C. Whitfield, Eleanor J. Apweiler, Rolf Koyanagi, Kanako O. Khurana, Jitendra P. Raghuvanshi, Saurabh Singh, Nagendra K. Tyagi, Akhilesh K. Haberer, Georg Fujisawa, Masaki Hosokawa, Satomi Ito, Yukiyo Ikawa, Hiroshi Shibata, Michie Yamamoto, Mayu Bruskiewich, Richard M. Hoen, Douglas R. Bureau, Thomas E. Namiki, Nobukazu Ohyanagi, Hajime Sakai, Yasumichi Nobushima, Satoshi Sakata, Katsumi Barrero, Roberto A. Sato, Yutaka Souvorov, Alexandre Smith-White, Brian Tatusova, Tatiana An, Suyoung An, Gynheung OOta, Satoshi Fuks, Galina Messing, Joachim Christie, Karen R. Lieberherr, Damien Kim, HyeRan Zuccolo, Andrea Wing, Rod A. Nobuta, Kan Green, Pamela J. Lu, Cheng Meyers, Blake C. Chaparro, Cristian Piegu, Benoit Panaud, Olivier Echeverria, Manuel TI The rice annotation project database (RAP-DB): 2008 update SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SATIVA SSP JAPONICA; DNA TAGGING LINES; T-DNA; ORYZA-SATIVA; FUNCTIONAL GENOMICS; INSERTIONAL MUTAGENESIS; ARABIDOPSIS-THALIANA; REVERSE GENETICS; GENERATION; SEQUENCE AB The Rice Annotation Project Database (RAP-DB) was created to provide the genome sequence assembly of the International Rice Genome Sequencing Project (IRGSP), manually curated annotation of the sequence, and other genomics information that could be useful for comprehensive understanding of the rice biology. Since the last publication of the RAP-DB, the IRGSP genome has been revised and reassembled. In addition, a large number of rice-expressed sequence tags have been released, and functional genomics resources have been produced worldwide. Thus, we have thoroughly updated our genome annotation by manual curation of all the functional descriptions of rice genes. The latest version of the RAP-DB contains a variety of annotation data as follows: clone positions, structures and functions of 31 439 genes validated by cDNAs, RNA genes detected by massively parallel signature sequencing (MPSS) technology and sequence similarity, flanking sequences of mutant lines, transposable elements, etc. Other annotation data such as Gnomon can be displayed along with those of RAP for comparison. We have also developed a new keyword search system to allow the user to access useful information.TheRAP-DB is available at: http://rapdb.dna.affrc.go.jp/ and http://rapdb.lab.nig.ac.jp/. C1 [Tanaka, Tsuyoshi; Antonio, Baltazar A.; Kikuchi, Shoshi; Matsumoto, Takashi; Nagamura, Yoshiaki; Numa, Hisataka; Sakai, Hiroaki; Wu, Jianzhong; Itoh, Takeshi; Sasaki, Takuji] Natl Inst Agrobiol Sci, Tsukuba 3058602, Japan. [Itoh, Takeshi; Imanishi, Tadashi] Natl Inst Adv Ind Sci & Technol, Biol Informat Res Ctr, Nagoya, Aichi, Japan. [Aono, Ryo; Fujii, Yasuyuki; Habara, Takuya; Harada, Erimi; Kanno, Masako; Kawahara, Yoshihiro; Kawashima, Hiroaki; Kubooka, Hiromi; Matsuya, Akihiro; Nakaoka, Hajime; Saichi, Naomi; Sanbonmatsu, Ryoko; Sato, Yoshiharu; Shinso, Yuji; Suzuki, Mami; Takeda, Jun-Ichi; Tanino, Motohiko; Todokoro, Fusano; Yamaguchi, Kaori; Yamamoto, Naoyuki; Yamasaki, Chisato] Japan Biol Informat Consortium, Tokyo 1350064, Japan. [Fujii, Yasuyuki] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Innovat Ctr Okayama Nanobiotargeted Therapy, Okayama 7008558, Japan. [Kawahara, Yoshihiro] Tokyo Metropolitan Univ, Dept Biol Sci, Tokyo 1920397, Japan. Natl Inst Genet, Res Org Informat & Syst, Ctr Informat Biol, Shizuoka 4118540, Japan. [Okido, Toshihisa; Tada, Masahito; Ikeo, Kazuho; Tateno, Yoshio; Gojobori, Takashi; Barrero, Roberto A.] Natl Inst Genet, Res Org Informat & Syst, DNA Data Bank Japan, Shizuoka 4118540, Japan. [Lin, Yao-Cheng; Wei, Fu-Jin] Acad Sinica, Inst Bot, Taipei 11529, Taiwan. [Zhao, Qiang; Han, Bin] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200233, Peoples R China. [Kramer, Melissa R.; McCombie, Richard W.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11723 USA. [Lonsdale, David; O'Donovan, Claire C.; Whitfield, Eleanor J.; Apweiler, Rolf] European Bioinformat Inst, Cambridge CB10 1SD, England. [Koyanagi, Kanako O.] Hokkaido Univ, Grad Sch Informat Sci & Technol, Hokkaido 0600814, Japan. [Khurana, Jitendra P.; Raghuvanshi, Saurabh; Tyagi, Akhilesh K.] Univ Delhi, Dept Plant Mol Biol, New Delhi 110021, India. [Singh, Nagendra K.] Indian Agr Res Inst, Natl Res Ctr Plant Biotechnol, New Delhi 110012, India. [Haberer, Georg] GSF Natl Res Ctr Environm & Hlth, MIPS, Inst Bioinformat, D-85764 Neuherberg, Germany. [Fujisawa, Masaki; Hosokawa, Satomi; Ito, Yukiyo; Ikawa, Hiroshi; Shibata, Michie; Yamamoto, Mayu] Inst Soc Technoinnovat Agr Forestry & Fisheries, Tsukuba 3050854, Japan. [Bruskiewich, Richard M.] Int Rice Res Inst, Crop Res Informat Lab, Manila, Philippines. [Hoen, Douglas R.; Bureau, Thomas E.] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada. [Namiki, Nobukazu; Ohyanagi, Hajime; Sakai, Yasumichi; Nobushima, Satoshi; Sakata, Katsumi] Mitsubishi Space Software Co Ltd, Tsukuba Div, Tsukuba 3050032, Japan. [Barrero, Roberto A.] Murdoch Univ, Ctr Comparat Genom, Murdoch, WA 6150, Australia. [Sato, Yutaka] Nagoya Univ, Grad Sch Bioagr Sci, Nagoya, Aichi 4648601, Japan. [Souvorov, Alexandre; Smith-White, Brian; Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [An, Suyoung; An, Gynheung] Pohang Univ Sci & Technol, Pohang 790784, South Korea. [OOta, Satoshi] RIKEN Tsukuba Inst, RIKEN BioResource Ctr, Tsukuba 3050074, Japan. [Fuks, Galina; Messing, Joachim] Rutgers State Univ, Waksman Inst Microbiol, Piscataway, NJ 08854 USA. [Christie, Karen R.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Lieberherr, Damien] Swiss Inst Bioinformat, Swiss Port Grp, CH-1206 Geneva, Switzerland. [Kim, HyeRan; Zuccolo, Andrea; Wing, Rod A.] Univ Arizona, Arizona Genom Inst, Tucson, AZ 85721 USA. [Nobuta, Kan; Green, Pamela J.; Lu, Cheng; Meyers, Blake C.] Univ Delaware, Newark, DE 19711 USA. [Chaparro, Cristian; Piegu, Benoit; Panaud, Olivier; Echeverria, Manuel] Univ Perpignan, CNRS, UMR, IRD, F-66860 Perpignan, France. RP Itoh, T (reprint author), Natl Inst Agrobiol Sci, Tsukuba 3058602, Japan. EM taitoh@affrc.go.jp RI LIN, Yao-Cheng/B-4394-2008; TYAGI, AKHILESH KUMAR/D-2649-2009; Koyanagi, Kanako/D-6354-2012; Jun-ichi, Takeda/I-7483-2014; Meyers, Blake/B-6535-2012; OI LIN, Yao-Cheng/0000-0002-9390-795X; Koyanagi, Kanako/0000-0003-1615-5077; Jun-ichi, Takeda/0000-0001-5367-5608; Meyers, Blake/0000-0003-3436-6097; Christie, Karen/0000-0001-5501-853X; O'Donovan, Claire/0000-0001-8051-7429 NR 32 TC 196 Z9 1940 U1 4 U2 31 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2008 VL 36 SI SI BP D1028 EP D1033 DI 10.1093/nar/gkm978 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253VJ UT WOS:000252545400179 ER PT J AU Waters, M Stasiewicz, S Merrick, BA Tomer, K Bushel, P Paules, R Stegman, N Nehls, G Yost, KJ Johnson, CH Gustafson, SF Xirasagar, S Xiao, N Huang, CC Boyer, P Chan, DD Pan, Q Gong, H Taylor, J Choi, D Rashid, A Ahmed, A Howle, R Selkirk, J Tennant, R Fostel, J AF Waters, Michael Stasiewicz, Stanley Merrick, B. Alex Tomer, Kenneth Bushel, Pierre Paules, Richard Stegman, Nancy Nehls, Gerald Yost, Kenneth J. Johnson, C. Harris Gustafson, Scott F. Xirasagar, Sandhya Xiao, Nianqing Huang, Cheng-Cheng Boyer, Paul Chan, Denny D. Pan, Qinyan Gong, Hui Taylor, John Choi, Danielle Rashid, Asif Ahmed, Ayazaddin Howle, Reese Selkirk, James Tennant, Raymond Fostel, Jennifer TI CEBS - Chemical Effects in Biological Systems: a public data repository integrating study design and toxicity data with microarray and proteomics data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION PATTERNS; LIVED DAF-2 MUTANTS; RAT-LIVER; CAENORHABDITIS-ELEGANS; OBJECT MODEL; PROFILES; RESOURCE; MIAME; ACETAMINOPHEN; INFORMATION AB CEBS (Chemical Effects in Biological Systems) is an integrated public repository for toxicogenomics data, including the study design and timeline, clinical chemistry and histopathology findings and microarray and proteomics data. CEBS contains data derived from studies of chemicals and of genetic alterations, and is compatible with clinical and environmental studies. CEBS is designed to permit the user to query the data using the study conditions, the subject responses and then, having identified an appropriate set of subjects, to move to the microarray module of CEBS to carry out gene signature and pathway analysis. Scope of CEBS: CEBS currently holds 22 studies of rats, four studies of mice and one study of Caenorhabditis elegans. CEBS can also accommodate data from studies of human subjects. Toxicogenomics studies currently in CEBS comprise over 4000 microarray hybridizations, and 75 2D gel images annotated with protein identification performed by MALDI and MS/MS. CEBS contains raw microarray data collected in accordance with MIAME guidelines and provides tools for data selection, pre-processing and analysis resulting in annotated lists of genes of interest. Additionally, clinical chemistry and histopathology findings from over 1500 animals are included in CEBS. CEBS/BID: The BID (Biomedical Investigation Database) is another component of the CEBS system. BID is a relational database used to load and curate study data prior to export to CEBS, in addition to capturing and displaying novel data types such as PCR data, or additional fields of interest, including those defined by the HESI Toxicogenomics Committee (in preparation). BID has been shared with Health Canada and the US Environmental Protection Agency. CEBS is available at http://cebs.niehs.nih.gov. BID can be accessed via the user interface from https://dir-apps.niehs.nih.gov/arc/. Requests for a copy of BID and for depositing data into CEBS or BID are available at http://www.niehs.nih.gov/cebs-df/. C1 [Choi, Danielle; Rashid, Asif; Fostel, Jennifer] Lockheed Martin Informat Technol, Res Triangle Pk, NC 27709 USA. [Waters, Michael; Stasiewicz, Stanley; Merrick, B. Alex; Tomer, Kenneth; Bushel, Pierre; Paules, Richard; Stegman, Nancy; Nehls, Gerald; Selkirk, James; Tennant, Raymond] NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. [Yost, Kenneth J.; Johnson, C. Harris; Gustafson, Scott F.; Xirasagar, Sandhya; Xiao, Nianqing; Huang, Cheng-Cheng; Boyer, Paul; Chan, Denny D.; Pan, Qinyan; Gong, Hui] Sci Applicat Int Corp, Mclean, VA 22101 USA. [Taylor, John] Large Scale Biol Corp, Vacaville, CA 95688 USA. [Choi, Danielle] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Ahmed, Ayazaddin; Howle, Reese] Alpha Gamma Technol Inc, Raleigh, NC 27609 USA. RP Fostel, J (reprint author), Lockheed Martin Informat Technol, POB 12233, Res Triangle Pk, NC 27709 USA. EM fostel@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS NR 38 TC 77 Z9 78 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2008 VL 36 SI SI BP D892 EP D900 DI 10.1093/nar/gkm755 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253VJ UT WOS:000252545400157 PM 17962311 ER PT J AU Wheeler, DL Barrett, T Benson, DA Bryant, SH Canese, K Chetvernin, V Church, DM DiCuccio, M Edgar, R Federhen, S Feolo, M Geer, LY Helmberg, W Kapustin, Y Khovayko, O Landsman, D Lipman, DJ Madden, TL Maglott, DR Miller, V Ostell, J Pruitt, KD Schuler, GD Shumway, M Sequeira, E Sherry, ST Sirotkin, K Souvorov, A Starchenko, G Tatusov, RL Tatusova, TA Wagner, L Yaschenko, E AF Wheeler, David L. Barrett, Tanya Benson, Dennis A. Bryant, Stephen H. Canese, Kathi Chetvernin, Vyacheslav Church, Deanna M. DiCuccio, Michael Edgar, Ron Federhen, Scott Feolo, Michael Geer, Lewis Y. Helmberg, Wolfgang Kapustin, Yuri Khovayko, Oleg Landsman, David Lipman, David J. Madden, Thomas L. Maglott, Donna R. Miller, Vadim Ostell, James Pruitt, Kim D. Schuler, Gregory D. Shumway, Martin Sequeira, Edwin Sherry, Steven T. Sirotkin, Karl Souvorov, Alexandre Starchenko, Grigory Tatusov, Roman L. Tatusova, Tatiana A. Wagner, Lukas Yaschenko, Eugene TI Database resources of the national center for biotechnology information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SEARCH; SEQUENCE; ENTREZ; ALGORITHM; GENES; TOOL AB In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data available through NCBIs web site. NCBI resources include Entrez, the Entrez Programming Utilities, My NCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link, Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genome, Genome Project and related tools, the Trace, Assembly, and Short Read Archives, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups, Influenza Viral Resources, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus, Entrez Probe, GENSAT, Database of Genotype and Phenotype, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool and the PubChem suite of small molecule databases. Augmenting the web applications are custom implementations of the BLAST program optimized to search specialized data sets. These resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov. C1 [Wheeler, David L.; Barrett, Tanya; Benson, Dennis A.; Bryant, Stephen H.; Canese, Kathi; Chetvernin, Vyacheslav; Church, Deanna M.; DiCuccio, Michael; Edgar, Ron; Federhen, Scott; Feolo, Michael; Geer, Lewis Y.; Helmberg, Wolfgang; Kapustin, Yuri; Khovayko, Oleg; Landsman, David; Lipman, David J.; Madden, Thomas L.; Maglott, Donna R.; Miller, Vadim; Ostell, James; Pruitt, Kim D.; Schuler, Gregory D.; Shumway, Martin; Sequeira, Edwin; Sherry, Steven T.; Sirotkin, Karl; Souvorov, Alexandre; Starchenko, Grigory; Tatusov, Roman L.; Tatusova, Tatiana A.; Wagner, Lukas; Yaschenko, Eugene] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wheeler, DL (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM wheeler@ncbi.nlm.nih.gov RI Landsman, David/C-5923-2009; Geer, Lewis/H-2714-2014; OI Landsman, David/0000-0002-9819-6675 FU Intramural NIH HHS [Z99 LM999999] NR 40 TC 437 Z9 450 U1 2 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2008 VL 36 SI SI BP D13 EP D21 DI 10.1093/nar/gkm1000 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253VJ UT WOS:000252545400004 PM 18045790 ER PT J AU Yamasaki, C Murakami, K Fujii, Y Sato, Y Harada, E Takeda, JI Taniya, T Sakate, R Kikugawa, S Shimada, M Tanino, M Koyanagi, KO Barrero, RA Gough, C Chun, HW Habara, T Hanaoka, H Hayakawa, Y Hilton, PB Kaneko, Y Kanno, M Kawahara, Y Kawamura, T Matsuya, A Nagata, N Nishikata, K Noda, AO Nurimoto, S Saichi, N Sakai, H Sanbonmatsu, R Shiba, R Suzuki, M Takabayashi, K Takahashi, A Tamura, T Tanaka, M Tanaka, S Todokoro, F Yamaguchi, K Yamamoto, N Okido, T Mashima, J Hashizume, A Jin, L Lee, KB Lin, YC Nozaki, A Sakai, K Tada, M Miyazaki, S Makino, T Ohyanagi, H Osato, N Tanaka, N Suzuki, Y Ikeo, K Saitou, N Sugawara, H O'Donovan, C Kulikova, T Whitfield, E Halligan, B Shimoyama, M Twigger, S Yura, K Kimura, K Yasuda, T Nishikawa, T Akiyama, Y Motono, C Mukai, Y Nagasaki, H Suwa, M Horton, P Kikuno, R Ohara, O Lancet, D Eveno, E Graudens, E Imbeaud, S Debily, MA Hayashizaki, Y Amid, C Han, M Osanger, A Endo, T Thomas, MA Hirakawa, M Makalowski, W Nakao, M Kim, NS Yoo, HS De Souza, SJ Bonaldo, MD Niimura, Y Kuryshev, V Schupp, I Wiemann, S Bellgard, M Shionyu, M Jia, L Thierry-Mieg, D Thierry-Mieg, J Wagner, L Zhang, Q Go, M Minoshima, S Ohtsubo, M Hanada, K Tonellato, P Isogai, T Zhang, J Lenhard, B Kim, S Chen, Z Hinz, U Estreicher, A Nakai, K Makalowska, I Hide, W Tiffin, N Wilming, L Chakraborty, R Soares, MB Chiusano, ML Suzuki, Y Auffray, C Yamaguchi-Kabata, Y Itoh, T Hishiki, T Fukuchi, S Nishikawa, K Sugano, S Nomura, N Tateno, Y Imanishi, T Gojobori, T AF Yamasaki, Chisato Murakami, Katsuhiko Fujii, Yasuyuki Sato, Yoshiharu Harada, Erimi Takeda, Jun-Ichi Taniya, Takayuki Sakate, Ryuichi Kikugawa, Shingo Shimada, Makoto Tanino, Motohiko Koyanagi, Kanako O. Barrero, Roberto A. Gough, Craig Chun, Hong-Woo Habara, Takuya Hanaoka, Hideki Hayakawa, Yosuke Hilton, Phillip B. Kaneko, Yayoi Kanno, Masako Kawahara, Yoshihiro Kawamura, Toshiyuki Matsuya, Akihiro Nagata, Naoki Nishikata, Kensaku Noda, Akiko Ogura Nurimoto, Shin Saichi, Naomi Sakai, Hiroaki Sanbonmatsu, Ryoko Shiba, Rie Suzuki, Mami Takabayashi, Kazuhiko Takahashi, Aiko Tamura, Takuro Tanaka, Masayuki Tanaka, Susumu Todokoro, Fusano Yamaguchi, Kaori Yamamoto, Naoyuki Okido, Toshihisa Mashima, Jun Hashizume, Aki Jin, Lihua Lee, Kyung-Bum Lin, Yi-Chueh Nozaki, Asami Sakai, Katsunaga Tada, Masahito Miyazaki, Satoru Makino, Takashi Ohyanagi, Hajime Osato, Naoki Tanaka, Nobuhiko Suzuki, Yoshiyuki Ikeo, Kazuho Saitou, Naruya Sugawara, Hideaki O'Donovan, Claire Kulikova, Tamara Whitfield, Eleanor Halligan, Brian Shimoyama, Mary Twigger, Simon Yura, Kei Kimura, Kouichi Yasuda, Tomohiro Nishikawa, Tetsuo Akiyama, Yutaka Motono, Chie Mukai, Yuri Nagasaki, Hideki Suwa, Makiko Horton, Paul Kikuno, Reiko Ohara, Osamu Lancet, Doron Eveno, Eric Graudens, Esther Imbeaud, Sandrine Debily, Marie Anne Hayashizaki, Yoshihide Amid, Clara Han, Michael Osanger, Andreas Endo, Toshinori Thomas, Michael A. Hirakawa, Mika Makalowski, Wojciech Nakao, Mitsuteru Kim, Nam-Soon Yoo, Hyang-Sook De Souza, Sandro J. Bonaldo, Maria de Fatima Niimura, Yoshihito Kuryshev, Vladimir Schupp, Ingo Wiemann, Stefan Bellgard, Matthew Shionyu, Masafumi Jia, Libin Thierry-Mieg, Danielle Thierry-Mieg, Jean Wagner, Lukas Zhang, Qinghua Go, Mitiko Minoshima, Shinsei Ohtsubo, Masafumi Hanada, Kousuke Tonellato, Peter Isogai, Takao Zhang, Ji Lenhard, Boris Kim, Sangsoo Chen, Zhu Hinz, Ursula Estreicher, Anne Nakai, Kenta Makalowska, Izabela Hide, Winston Tiffin, Nicola Wilming, Laurens Chakraborty, Ranajit Soares, Marcelo Bento Chiusano, Maria Luisa Suzuki, Yutaka Auffray, Charles Yamaguchi-Kabata, Yumi Itoh, Takeshi Hishiki, Teruyoshi Fukuchi, Satoshi Nishikawa, Ken Sugano, Sumio Nomura, Nobuo Tateno, Yoshio Imanishi, Tadashi Gojobori, Takashi TI The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENOMIC DNA; PROTEINS; PREDICTION; SEQUENCE AB Here we report the new features and improvements in our latest release of the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/), a comprehensive annotation resource for human genes and transcripts. H-InvDB, originally developed as an integrated database of the human transcriptome based on extensive annotation of large sets of full-length cDNA (FLcDNA) clones, now provides annotation for 120 558 human mRNAs extracted from the International Nucleotide Sequence Databases (INSD), in addition to 54 978 human FLcDNAs, in the latest release H-InvDB_4.6. We mapped those human transcripts onto the human genome sequences (NCBI build 36.1) and determined 34 699 human gene clusters, which could define 34 057 (98.1%) protein-coding and 642 (1.9%) non-protein-coding loci; 858 (2.5%) transcribed loci overlapped with predicted pseudogenes. For all these transcripts and genes, we provide comprehensive annotation including gene structures, gene functions, alternative splicing variants, functional non-protein-coding RNAs, functional domains, predicted sub cellular localizations, metabolic pathways, predictions of protein 3D structure, mapping of SNPs and microsatellite repeat motifs, co-localization with orphan diseases, gene expression profiles, orthologous genes, proteinprotein interactions (PPI) and annotation for gene families. The current H-InvDB annotation resources consist of two main views: Transcript view and Locus view and eight sub-databases: the DiseaseInfo Viewer, H-ANGEL, the Clustering Viewer, G-integra, the TOPO Viewer, Evola, the PPI view and the Gene family/group. C1 [Yamasaki, Chisato; Murakami, Katsuhiko; Sato, Yoshiharu; Harada, Erimi; Takeda, Jun-Ichi; Taniya, Takayuki; Sakate, Ryuichi; Kikugawa, Shingo; Shimada, Makoto; Gough, Craig; Chun, Hong-Woo; Hilton, Phillip B.; Kanno, Masako; Kawahara, Yoshihiro; Noda, Akiko Ogura; Saichi, Naomi; Sanbonmatsu, Ryoko; Shiba, Rie; Suzuki, Mami; Takahashi, Aiko; Tanaka, Masayuki; Yamaguchi-Kabata, Yumi; Itoh, Takeshi; Hishiki, Teruyoshi; Sugano, Sumio; Nomura, Nobuo; Imanishi, Tadashi; Gojobori, Takashi] Natl Inst Adv Ind Sci & Technol, Biol Informat Res Ctr, Tokyo, Japan. [Yamasaki, Chisato; Murakami, Katsuhiko; Harada, Erimi; Takeda, Jun-Ichi; Taniya, Takayuki; Sakate, Ryuichi; Kikugawa, Shingo; Shimada, Makoto; Gough, Craig; Chun, Hong-Woo; Habara, Takuya; Hayakawa, Yosuke; Hilton, Phillip B.; Kanno, Masako; Kawahara, Yoshihiro; Matsuya, Akihiro; Nishikata, Kensaku; Noda, Akiko Ogura; Saichi, Naomi; Sanbonmatsu, Ryoko; Shiba, Rie; Suzuki, Mami; Takahashi, Aiko; Todokoro, Fusano; Yamaguchi, Kaori; Yamamoto, Naoyuki] Japan Biol Informat Consortium, Japan Biol Informat Res Ctr, Tokyo, Japan. [Fujii, Yasuyuki] Okayama Univ, Grad Sch Med, Dent & Pharmaceut Sci, Okayama, Japan. [Tanino, Motohiko] DNA Chip Res Inc, Kanagawa, Japan. [Koyanagi, Kanako O.; Endo, Toshinori; Imanishi, Tadashi] Hokkaido Univ, Sapporo, Hokkaido 060, Japan. [Bellgard, Matthew] Murdoch Univ, Ctr Comparat Genom, Murdoch, WA 6150, Australia. [Hanaoka, Hideki] Univ Tokyo, Biotechnol Res Ctr, Tokyo, Japan. [Hayakawa, Yosuke] Hitachi Software Engn Co Ltd, Tokyo, Japan. [Kaneko, Yayoi] Mitsubishi Kagaku Inst Life Sci, Tokyo, Japan. [Kawamura, Toshiyuki] Fujitsu Ltd, Tokyo, Japan. [Matsuya, Akihiro] Hitachi Co Ltd, Hatoyama, Saitama, Japan. [Nagata, Naoki] Japan Sci & Technol Agcy, Tokyo, Japan. [Nishikata, Kensaku] NEC Soft Ltd, Tokyo, Japan. [Nurimoto, Shin] Mitsui Knowledge Ind Co Ltd, Tokyo, Japan. [Sakai, Hiroaki] Natl Inst Agrobiol Sci, Ibaraki, Japan. [Tamura, Takuro] BITS Co Ltd, Shizuoka, Japan. [Tanaka, Susumu] Tokyo Inst Psychiatry, Tokyo, Japan. [Todokoro, Fusano] Dynacom Co Ltd, Chiba, Japan. [Okido, Toshihisa; Mashima, Jun; Hashizume, Aki; Jin, Lihua; Lee, Kyung-Bum; Lin, Yi-Chueh; Nozaki, Asami; Sakai, Katsunaga; Ohyanagi, Hajime; Osato, Naoki; Tanaka, Nobuhiko; Suzuki, Yoshiyuki; Ikeo, Kazuho; Sugawara, Hideaki; Hishiki, Teruyoshi; Fukuchi, Satoshi; Nishikawa, Ken; Tateno, Yoshio; Gojobori, Takashi] Natl Inst Genet, DNA Data Bank, Shizuoka, Japan. [Okido, Toshihisa; Mashima, Jun; Hashizume, Aki; Jin, Lihua; Lee, Kyung-Bum; Lin, Yi-Chueh; Nozaki, Asami; Sakai, Katsunaga; Tada, Masahito; Ohyanagi, Hajime; Osato, Naoki; Tanaka, Nobuhiko; Suzuki, Yoshiyuki; Ikeo, Kazuho; Sugawara, Hideaki; Fukuchi, Satoshi; Nishikawa, Ken; Tateno, Yoshio; Gojobori, Takashi] Ctr Informat Biol, Shizuoka, Japan. [Miyazaki, Satoru] Tokyo Univ Sci, Chiba, Japan. [Makino, Takashi] Dublin City Univ, Trinity Coll, Dublin, Ireland. [Ohyanagi, Hajime] Mitsubhishi Space Software Co Ltd, Ibaraki, Japan. [Saitou, Naruya] Natl Inst Genet, Div Populat Genet, Shizuoka, Japan. [O'Donovan, Claire; Kulikova, Tamara; Whitfield, Eleanor] EMBL Outstn Hinxton, European Bioinformat Inst, Cambridge, England. [Halligan, Brian; Shimoyama, Mary; Twigger, Simon] Med Coll Wisconsin, Bioinformat Res Ctr, Milwaukee, WI USA. [Yura, Kei] Japan Atom Energy Agcy, Ctr Computat Sci & Engn, Kyoto, Japan. [Kimura, Kouichi; Yasuda, Tomohiro; Nishikawa, Tetsuo] Hitachi Ltd, Cent Res Lab, Hatoyama, Saitama, Japan. [Akiyama, Yutaka; Motono, Chie; Mukai, Yuri; Nagasaki, Hideki; Suwa, Makiko; Horton, Paul] Natl Inst Adv Ind Sci & Technol, Computat Biol Res Ctr, Tokyo, Japan. [Kikuno, Reiko; Ohara, Osamu] Kazusa DNA Res Inst, Dept Human Gene, Chiba, Japan. [Lancet, Doron] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. [Eveno, Eric; Graudens, Esther; Imbeaud, Sandrine; Debily, Marie Anne] CNRS, Villejuif, France. [Eveno, Eric; Graudens, Esther; Imbeaud, Sandrine; Debily, Marie Anne] Univ Paris 06, Villejuif, France. [Eveno, Eric; Graudens, Esther; Imbeaud, Sandrine; Debily, Marie Anne; Zhang, Qinghua] Sino French Lab Lif Sci & Genom, Shanghai, Peoples R China. [Imbeaud, Sandrine] CNRS, Ctr Gent Mol, Gif Sur Yvette, France. [Imbeaud, Sandrine] Gif Orsay DNA Microarray Platform, Gif Sur Yvette, France. [Debily, Marie Anne] IRCM, DSV, CEA, Lab Genomes Funct Explorat, Evry, France. [Hayashizaki, Yoshihide] RIKEN, Yokohama Inst, Genom Sci Ctr, Kanagawa, Japan. [Hayashizaki, Yoshihide] RIKEN, Wako Inst, Discovery & Res Inst, Genome Sci Lab, Saitama, Japan. [Amid, Clara; Han, Michael; Osanger, Andreas] GSF, Natl Res Ctr Environm & Hlth, Inst Bioinformat, Neuherberg, Germany. [Thomas, Michael A.] Idaho State Univ, Pocatello, ID 83209 USA. [Hirakawa, Mika] Kyoto Univ, Inst Chem Res, Kyoto, Japan. [Makalowski, Wojciech] Univ Munster, Inst Bioinformat, Munster, Germany. [Nakao, Mitsuteru] Kazusa DNA Res Inst, Chiba, Japan. [Kim, Nam-Soon; Yoo, Hyang-Sook] Korea Res Inst Biosci & Biotechnol, Taejon, South Korea. [De Souza, Sandro J.] Ludwig Inst Canc Res, Sao Paulo, Brazil. [Bonaldo, Maria de Fatima] Univ Iowa, Med Educ & Biomed Res Facility, Iowa City, IA 52242 USA. [Niimura, Yoshihito] Tokyo Med & Dent Univ, Inst Med Res, Tokyo, Japan. [Kuryshev, Vladimir; Schupp, Ingo; Wiemann, Stefan] German Canc Res Ctr, Mol Genome Anal, D-6900 Heidelberg, Germany. [Shionyu, Masafumi] Nagahama Inst Bio Sci & Technol, Shiga, Japan. [Jia, Libin] Natl Inst Hlth, Natl Canc Inst, Baltimore, MD USA. [Thierry-Mieg, Danielle; Thierry-Mieg, Jean; Wagner, Lukas] Natl Lib Med, Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Zhang, Qinghua] Natl Engn Ctr Biochips, Shanghai, Peoples R China. [Go, Mitiko] Ochanomizu Univ, Tokyo 112, Japan. [Minoshima, Shinsei; Ohtsubo, Masafumi] Hamamatsu Univ Sch Med, Photon Med Res Ctr, Shizuoka, Japan. [Hanada, Kousuke] RIKEN, Yokohama Inst, Plant Sci Ctr, Kanagawa, Japan. [Tonellato, Peter] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Zhang, Ji] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China. [Lenhard, Boris] Karolinska Inst, Ctr Genom & Bioinformat, Stockholm, Sweden. [Kim, Sangsoo] Soongsil Univ, Seoul, South Korea. [Chen, Zhu] Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, Shanghai Inst Hematol,State Key Lab Med Genom, Shanghai, Peoples R China. [Chen, Zhu] Chinese Natl Human Genome Ctr, Shanghai, Peoples R China. [Hinz, Ursula; Estreicher, Anne] Swiss Ins Bioinformat, Geneva, Switzerland. [Nakai, Kenta] Univ Tokyo, Inst Med Sci, Tokyo, Japan. [Makalowska, Izabela] Penn State Univ, University Pk, PA 16802 USA. [Hide, Winston; Tiffin, Nicola] Univ Western Cape, S African Natl Bioinformat Inst, Cape Town, South Africa. [Wilming, Laurens] Well Trust Sanger Inst, Cambridge, England. [Chakraborty, Ranajit] Univ Cincinnati, Cincinnati, OH 45221 USA. [Soares, Marcelo Bento] Northwestern Univ, Feinberg Sch med, Childrens Mem Res Ctr, Evanston, IL 60208 USA. [Chiusano, Maria Luisa] Univ Naples Federico II, Naples, Italy. [Suzuki, Yutaka; Sugano, Sumio] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Tokyo, Japan. RP Imanishi, T (reprint author), Natl Inst Adv Ind Sci & Technol, Biol Informat Res Ctr, Tokyo, Japan. EM t.imanishi@aist.go.jp; tgojobor@genes.nig.ac.jp RI Paulini, Michael/E-8289-2017; THIERRY-MIEG, Jean/F-1975-2017; Shimada, Makoto/K-4613-2015; Ohara, Osamu/G-5448-2015; Nakai, Kenta/B-7293-2009; Hide, Winston Hide/C-7217-2009; Makalowski, Wojciech/I-2843-2016; murakami, katsuhiko/C-2083-2009; Ohara, Osamu/A-9119-2012; Koyanagi, Kanako/D-6354-2012; Thomas, Michael/B-7489-2008; Tiffin, Nicki/A-5914-2013; Imunologia, Inct/I-2124-2013; Wiemann, Stefan/E-4424-2013; Halligan, Brian/N-5166-2015; Jun-ichi, Takeda/I-7483-2014; Hayashizaki, Yoshihide/N-6590-2015 OI O'Donovan, Claire/0000-0001-8051-7429; Paulini, Michael/0000-0002-6968-2340; THIERRY-MIEG, Jean/0000-0002-0396-6789; Amid, Clara/0000-0001-6534-7425; Shimada, Makoto/0000-0003-0067-0082; Wilming, Laurens/0000-0002-4154-7358; Chiusano, Maria Luisa/0000-0002-6296-7132; Lenhard, Boris/0000-0002-1114-1509; Ohara, Osamu/0000-0002-3328-9571; Nakai, Kenta/0000-0002-8721-8883; Hide, Winston Hide/0000-0002-8621-3271; Koyanagi, Kanako/0000-0003-1615-5077; Thomas, Michael/0000-0003-2982-0291; Wiemann, Stefan/0000-0003-4683-3174; Halligan, Brian/0000-0002-9553-4253; Jun-ichi, Takeda/0000-0001-5367-5608; NR 22 TC 48 Z9 52 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2008 VL 36 SI SI BP D793 EP D799 DI 10.1093/nar/gkm999 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253VJ UT WOS:000252545400141 ER PT J AU Zeng, J Yan, J Wang, T Mosbrook-Davis, D Dolan, KT Christensen, R Stormo, GD Haussler, D Lathrop, RH Brachmann, RK Burgess, SM AF Zeng, Jue Yan, Jizhou Wang, Ting Mosbrook-Davis, Deborah Dolan, Kyle T. Christensen, Ryan Stormo, Gary D. Haussler, David Lathrop, Richard H. Brachmann, Rainer K. Burgess, Shawn M. TI Genome wide screens in yeast to identify potential binding sites and target genes of DNA-binding proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION-FACTOR; SACCHAROMYCES-CEREVISIAE; NF-Y; P53; SYSTEM; EXPRESSION; MICROARRAY; ZEBRAFISH; SELECTION; IDENTIFICATION AB Knowledge of all binding sites for transcriptional activators and repressors is essential for computationally aided identification of transcriptional networks. The techniques developed for defining the binding sites of transcription factors tend to be cumbersome and not adaptable to high throughput. We refined a versatile yeast strategy to rapidly and efficiently identify genomic targets of DNA-binding proteins. Yeast expressing a transcription factor is mated to yeast containing a library of genomic fragments cloned upstream of the reporter gene URA3. DNA fragments with target-binding sites are identified by growth of yeast clones in media lacking uracil. The experimental approach was validated with the tumor suppressor protein p53 and the forkhead protein FoxI1 using genomic libraries for zebrafish and mouse generated by shotgun cloning of short genomic fragments. Computational analysis of the genomic fragments recapitulated the published consensus-binding site for each protein. Identified fragments were mapped to identify the genomic context of each binding site. Our yeast screening strategy, combined with bioinformatics approaches, will allow both detailed and high-throughput characterization of transcription factors, scalable to the analysis of all putative DNA-binding proteins. C1 [Yan, Jizhou; Mosbrook-Davis, Deborah; Dolan, Kyle T.; Burgess, Shawn M.] NHGRI, Gen Technol Branch, Bethesda, MD 20892 USA. [Yan, Jizhou; Wang, Ting; Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. [Zeng, Jue; Brachmann, Rainer K.] Univ Calif Irvine, Div Hematol Oncol, Irvine, CA USA. [Wang, Ting; Christensen, Ryan; Stormo, Gary D.] Washington Univ, Dept Genet, St Louis, MO 63110 USA. [Stormo, Gary D.; Lathrop, Richard H.] Univ Calif Irvine, Dept Comp Sci & Biomed Engn, Irvine, CA USA. [Lathrop, Richard H.; Brachmann, Rainer K.] Univ Calif Irvine, Inst Genom & Bioinformat, Irvine, CA USA. [Lathrop, Richard H.; Brachmann, Rainer K.] Univ Calif Irvine, Dept Lab Med, Irvine, CA USA. RP Burgess, SM (reprint author), NHGRI, Gen Technol Branch, Bethesda, MD 20892 USA. EM burgess@mail.nih.gov RI Stormo, Gary/C-5367-2013; OI Stormo, Gary/0000-0001-6896-1850; Burgess, Shawn/0000-0003-1147-0596 FU Intramural NIH HHS; NHGRI NIH HHS [R01 HG000249, HG00249] NR 57 TC 15 Z9 15 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2008 VL 36 IS 1 AR e8 DI 10.1093/nar/gkm1117 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253VG UT WOS:000252545100008 PM 18086703 ER PT J AU Dowd, CL Sutch, BT Haworth, IS Eritja, R Marquez, VE Yang, AS AF Dowd, Casimir L. Sutch, Brian T. Haworth, Ian S. Eritja, Ramon Marquez, Victor E. Yang, Allen S. TI Incorporation of zebularine from its 2'-deoxyribonucleoside triphosphate derivative and activity as a template-coding nucleobase SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article DE zebularine; DNA methylation; 5-azacytidine; epigenetics ID DNA METHYLATION INHIBITOR; MYELODYSPLASTIC SYNDROME; HYPOMETHYLATING AGENT; CYTIDINE ANALOGS; CANCER-THERAPY; METHYLTRANSFERASE; 5-AZA-2'-DEOXYCYTIDINE; MECHANISM; CELLS; BASE AB Zebularine (1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one) was studied as both a 2'-deoxyribosyl 5'-triphosphate derivative and as a template incorporated into an oligonucleotide. Using a novel pyrosequencing assay, zebularine acted as cytosine analog and was incorporated into DNA with a template pairing profile most similar to cytosine, pairing with greatest efficiency opposite guanine in the template strand. Guanine was incorporated with greater affinity than adenine opposite a zebularine in the template strand. Computer modeling of base-pairing structures supported a better fit of zebularine opposite guanine than adenine. Zebularine acts as a cytosine analog, which supports its activity as an inhibitor of cytosine methyltransferase. C1 [Dowd, Casimir L.; Yang, Allen S.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Sutch, Brian T.; Haworth, Ian S.] Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90033 USA. [Haworth, Ian S.; Eritja, Ramon] CSIC, Inst Mol Biol, Barcelona, Spain. [Marquez, Victor E.] NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21701 USA. RP Yang, AS (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Jane Anne Nohl Div Hematol, 1441 Eastlake Ave, Los Angeles, CA 90033 USA. EM allenyan@usc.edu RI eritja, ramon/B-5613-2008 OI eritja, ramon/0000-0001-5383-9334 NR 39 TC 7 Z9 7 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2008 VL 27 IS 2 BP 131 EP 145 DI 10.1080/15257770701795888 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253KG UT WOS:000252516500004 PM 18205068 ER PT J AU Chun, MW Choi, SW Kang, TK Choi, WJ Kim, HO Gao, ZG Jacobson, KA Jeong, LS AF Chun, Moon Woo Choi, Sung Wook Kang, Tae Kyung Choi, Won Jun Kim, Hea Ok Gao, Zhan-Guo Jacobson, Kenneth A. Jeong, Lak Shin TI Synthesis of 3 '-acetamidoadenosine derivatives as potential A(3) adenosine receptor agonists SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article DE 3 '-acetamidoadenosines; human A(3) adenosine receptor; hydrogen bonding donor; hydroboration-oxidation; steric effects ID NUCLEOSIDES; SELECTIVITY; EFFICACY; BINDING; DESIGN AB On the basis of high binding affinity of 3'-aminoadenosine derivatives 2b at the human A(3) adenosine receptor (AR), 3'-acetamidoadenosine derivatives 3a-e were synthesized from 1,2:5,6-di-O-isopropylidene-D-glucose via stereoselective hydroboration as a key step. Although all synthesized compounds were totally devoid of binding affinity at the human A(3)AR, our results revealed that 3'-position of adenosine can only be tolerated with small size of a hydrogen bonding donor like hydroxyl or amino group in the binding site of human A(3)AR. C1 [Chun, Moon Woo; Choi, Sung Wook; Kang, Tae Kyung] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea. [Choi, Won Jun; Kim, Hea Ok; Jeong, Lak Shin] Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul, South Korea. [Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA. RP Chun, MW (reprint author), Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea. EM mwchun@snu.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 13 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2008 VL 27 IS 4 BP 408 EP 420 DI 10.1080/15257770801944436 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 286TC UT WOS:000254867900007 PM 18404574 ER PT J AU Talsma, A Grady, PA Feetham, S Heinrich, J Steinwachs, DM AF Talsma, AkkeNeel Grady, Patricia A. Feetham, Suzanne Heinrich, Jan Steinwachs, Donald M. TI The perfect storm - Patient safety and nursing shortages within the context of health policy and evidence-based practice SO NURSING RESEARCH LA English DT Article; Proceedings Paper CT Symposium in Tribute to Ada Sue Hinshaw CY MAY 11, 2006 CL Ann Arbor, MI SP Agcy Healthcare Res & Qual, Off Provost Univ Michigan, Univ Michigan Hlth Syst DE evidence-based practice; health policy; health system issues; nursing workforce shortages; patient safety ID CARE; INTERVENTIONS; MANAGEMENT; MORTALITY; TRIAL AB Dr. Ada Sue Hinshaw stepped down from her deanship at the University of Michigan School of Nursing, leading to a conference in honor of her legacy held in May 2006. The topic of the conference highlighted Dr. Hinshaw's accomplishments in the area of health policy and patient safety. The proceedings of the afternoon included four presentations. The common themes of the presentations incorporated the importance of public policy for patient safety, the need for health systems reforms, and the use of appropriate evidence-based practice to advance the nursing sciences. These and other perspectives of the speakers are discussed within the context of the broad categories of system reform, contributions from nursing research, and health policy focus. Finally, recommendations were given for the preferred future. C1 [Talsma, AkkeNeel] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Grady, Patricia A.] NINR, Bethesda, MD 20892 USA. [Steinwachs, Donald M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Heinrich, Jan] Hlth Policy Res & Dev, Washington, DC USA. [Feetham, Suzanne] Univ Wisconsin, Milwaukee, WI 53201 USA. [Feetham, Suzanne] US Hlth Resources & Serv Adm, US Hlth & Human Serv, Ctr Qual, Rockville, MD 20857 USA. RP Talsma, A (reprint author), Univ Michigan, Sch Nursing, Room 4154,400 N Ingalls, Ann Arbor, MI 48109 USA. EM antalsma@umich.edu NR 22 TC 5 Z9 5 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD JAN-FEB PY 2008 VL 57 IS 1 SU S BP S15 EP S21 DI 10.1097/01.NNR.0000280650.76191.ab PG 7 WC Nursing SC Nursing GA 250WU UT WOS:000252332800004 PM 18091297 ER PT J AU Stewart, J Ware, J Boysen, C Gulati, S Zhou, ZZ Rosenfeld, S Kopelovich, L Kennedy, AR AF Stewart, Jelena Ware, Jeffrey Boysen, Cecilie Gulati, Sandeep Zhou, Zhaozong Rosenfeld, Simon Kopelovich, Levy Kennedy, Ann R. TI Effects of Selenomethionine on the Gene Expression Profile of Cloned Human Prostate Cancer Cells Representing a Phenotypic Continuum of Cancer Progression SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article AB We previously characterized three cell clones that were derived by limiting dilution from a human prostate cancer cell line (LNCaP) representing a phenotypic continuum of cancer progression (1). The present study was undertaken to examine the effects of L-selenomethionine (SeM), a potential cancer chemopreventive agent, on the gene expression profile of the cultured cell clones. Following a three-day incubation period with SeM, total RNA was extracted, and the gene expression profile was evaluated using Affymetrix human HG U133A microarrays and analyzed by ViaLogy's (Altadena, CA) VMAxS (R) platform deploying quantum resonance interferometry (QRI) processing. The differentially expressed genes and corresponding biological processes were compared across the different treatments and cell types. Whereas SeM significantly affected RNA-DNA metabolism and protein transport and metabolism in all of the cell types evaluated, significant effects of SeM on genes mainly involved in the pathways of cell cycle, growth, differentiation, and apoptosis were observed only in the cell clone with a more malignant phenotype. C1 [Stewart, Jelena; Ware, Jeffrey; Zhou, Zhaozong; Kennedy, Ann R.] Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Boysen, Cecilie; Gulati, Sandeep] ViaLogy, Altadena, CA USA. [Rosenfeld, Simon; Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Ware, J (reprint author), Univ Penn, Sch Med, Dept Radiat Oncol, 195 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM jhware@mail.med.upenn.edu FU National Cancer Institute [N01-CN-15134] FX We thank Paolo Fortina (Professor of Medicine at Jefferson Medical College, Thomas Jefferson University in Philadelphia, PA) and Eric Rappaport (Scientific Director, Nuclei Acid/Protein Core Facility, Children's Hospital of Philadelphia, PA) for the preparation and hybridization of our RNA samples for the microarray analyses. We thank Kung-Hua Chang, Dhondup Pemba, and James K. Breaux, of ViaLogy for processing our data using the VMAxS platform as well as for help in the data analysis. This work was supported by a contract from the National Cancer Institute (N01-CN-15134). NR 10 TC 0 Z9 0 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2008 VL 60 IS 6 BP 826 EP 836 DI 10.1080/01635580802090193 PG 11 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 389QI UT WOS:000262109200014 PM 19005982 ER PT J AU Stratton, P Sinaii, N Segars, J Koziol, D Wesley, R Zimmer, C Winkel, C Nieman, LK AF Stratton, Pamela Sinaii, Ninet Segars, James Koziol, Deloris Wesley, Robert Zimmer, Carolyn Winkel, Craig Nieman, Lynnette K. TI Return of chronic pelvic pain from endometriosis after raloxifene treatment - A randomized controlled trial SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 9th World Congress on Endometriosis CY SEP 14-18, 2005 CL Maastricht, NETHERLANDS ID ESTROGEN-RECEPTOR MODULATORS; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; LAPAROSCOPIC EXCISION; HEALTH PROFILE; DRUG-THERAPY; FOLLOW-UP; CLASSIFICATION; PREMENOPAUSAL; AGONIST AB OBJECTIVE: To evaluate whether 6 months of raloxifene was effective in treatment of chronic pelvic pain in women with endometriosis. METHODS: Women with chronic pelvic pain and no endometriosis treatment for 6 months underwent laparoscopy for excision of all lesions. Those with biopsy-proven endometriosis were randomly allocated to raloxifene (180 mg) or placebo daily. A second laparoscopy was performed at 2 years, or earlier, if pain returned. Return of pain was defined as 2 months of pain equal to or more severe than that at study entry. Menstrual cycles and adverse events were recorded. The log rank test was used to compare the time to return of pain by drug group. Analyses were done as intent-to-treat. RESULTS: A total of 127 of 158 women underwent surgery. Of these, 93 had biopsy-confirmed endometriosis and were randomly assigned to study treatment, Menstrual cycle length, pelvic pain severity, quality of life, bone mineral density, and adverse events did not differ between treatment groups. The Data Safety Monitoring Committee terminated the study early when the raloxifene group experienced pain (P=.03) and had second surgery (P=.016) significantly sooner than the placebo group. Interestingly, biopsy-proven endometriosis was not associated with return of pain (P=.6). CONCLUSION: Raloxifene significantly shortened the time to return of chronic pelvic pain. Because recurrence of endometriosis lesions did not correlate with return of pain, other factors are implicated in pelvic pain. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www. clinicaltrials.gov, NCT00001848. C1 NICHD, RBMB, NIH, CRC,Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC USA. RP Stratton, P (reprint author), NICHD, RBMB, NIH, CRC,Biostat & Clin Epidemiol Serv, 10 Ctr Dr,MSC 1109,Bldg 10,1-3140, Bethesda, MD 20892 USA. EM ps79c@nih.gov FU Intramural NIH HHS [Z01 HD008737-07] NR 39 TC 51 Z9 53 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2008 VL 111 IS 1 BP 88 EP 96 DI 10.1097/01.AOG.0000297307.35024.b5 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 249AV UT WOS:000252199900012 PM 18165396 ER PT J AU Lowder, JL Park, AJ Ellison, R Ghetti, C Moalli, P Zyczynski, H Weber, AM AF Lowder, Jerry L. Park, Amy J. Ellison, Rennique Ghetti, Chiara Moalli, Pamela Zyczynski, Halina Weber, Anne M. TI The role of apical vaginal support in the appearance of anterior and posterior vaginal prolapse SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PELVIC ORGAN PROLAPSE; URINARY-INCONTINENCE; REPAIR AB OBJECTIVE: To describe how simulated apical support affects the appearance of prolapse in the anterior and posterior vagina using a modification of the Pelvic Organ Prolapse Quantification (POP-Q) examination. METHODS: Women with prolapse stage II or greater were examined using the POP-Q. To simulate apical support, the posterior blade of a standard Graves speculum was positioned over the posterior vagina to support the vaginal apex while remeasuring points Aa and Ba and over the anterior vagina to support the apex while remeasuring points Ap and Bp. Change in anterior and posterior POP-Q points and prolapse stage with apical support were calculated. RESULTS: One hundred ninety-seven women were enrolled with mean age of 62 +/- 14 years, median parity of 2 (range 0-8), and mean body mass index of 28 +/- 5 kg/m(2). By standard POP-Q, 36% had stage II prolapse, 54% had stage III, and 10% had stage IV prolapse. With simulated apical support, point Ba changed to stage 0 or I in 55% of cases and point Bp changed to stage 0 or I in 30% (P<.001 for each point). Mean change for point Ba with apical support was 3.5 +/- 2.6 cm and point Bp was 1.9 +/- 2.9 cm (P<.001). CONCLUSION: When the POP-Q examination is performed with simulated apical support, the critical role of level I vaginal support on the position of the anterior and posterior vagina, particularly the anterior vagina, becomes apparent. C1 Univ Pittsburgh, Magee Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Sci,Div Urogynecol, Pittsburgh, PA 15213 USA. Cleveland Clin, Sect Female Pelv Med & Reconstruct Surg, Cleveland, OH 44106 USA. NICHHD, Bethesda, MD 20892 USA. RP Lowder, JL (reprint author), Univ Pittsburgh, Magee Womens Hosp, Sch Med, Dept Obstet & Gynecol,Div Urogynecol, 300 Halket St, Pittsburgh, PA 15213 USA. EM jlowder@mail.magee.edu NR 13 TC 40 Z9 45 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2008 VL 111 IS 1 BP 152 EP 157 DI 10.1097/01.AOG.0000297309.25091.a0 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 249AV UT WOS:000252199900020 PM 18165404 ER PT J AU Castano-Vinyals, G Cantor, KP Malats, N Tardon, A Garcia-Closas, R Serra, C Carrato, A Rothman, N Vermeulen, R Silverman, D Dosemeci, M Kogevinas, M AF Castano-Vinyals, Gemma Cantor, Kenneth P. Malats, Nuria Tardon, Adonina Garcia-Closas, Reina Serra, Consol Carrato, Alfredo Rothman, Nathaniel Vermeulen, Roel Silverman, Debra Dosemeci, Mustafa Kogevinas, Manolis TI Air pollution and risk of urinary bladder cancer in a case-control study in Spain SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; LUNG-CANCER; EXPOSURE; MORTALITY; AEROSOL; EUROPE; COHORT; MEN AB Objectives: Air pollution has been associated with an increased risk for lung cancer. We examined whether long-term air pollution is associated with bladder cancer risk. Methods: Information from a case-control study in Spain that included 1219 incident cases and 1271 hospital controls was used. Information on residential history including several indicators of exposure to air pollution and other potential risk factors was collected in a face-to-face computerised personal interview. Odds ratios (OR) and 95% confidence intervals (95% CI) were adjusted for age, gender, region, smoking, occupation, water contaminants and diet. Results: Living more than 40 years in a city with a population of more than 100 000 was associated with an increased risk for bladder cancer overall (OR 1.30, 95% CI 1.04 to 1.63). Emissions of polycyclic aromatic hydrocarbons and diesel from industries near the residence, as evaluated by experts, were associated with an increased risk (OR 1.29, 95% CI 0.85 to 1.98), while lower or no excess risks were observed for other pollution-related variables. Odds ratios among never smokers tended to be higher than among smokers. Conclusions: The small to moderate positive associations found for several indices of air pollution and bladder cancer, while suggestive of excess risk, require further evaluation in other settings. C1 [Castano-Vinyals, Gemma; Malats, Nuria; Kogevinas, Manolis] Municipal Inst Med Res, Ctr Res Environm Epidemiol, Barcelona 08003, Spain. [Cantor, Kenneth P.; Rothman, Nathaniel; Silverman, Debra; Dosemeci, Mustafa] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Tardon, Adonina] Univ Oviedo, Oviedo, Spain. [Garcia-Closas, Reina] Hosp Univ Canarias, Unidad Invest, Tenerife, Spain. [Serra, Consol] Univ Pompeu Fabra, Barcelona, Spain. [Serra, Consol] Consorci Hosp Parc Tauli, Sabadell, Spain. [Carrato, Alfredo] Hosp Gen Elche, Elche, Spain. [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Kogevinas, Manolis] Univ Crete, Sch Med, Dept Social Med, Iraklion, Crete, Greece. [Kogevinas, Manolis] CIBERESP, Barcelona, Spain. RP Castano-Vinyals, G (reprint author), Municipal Inst Med Res, Ctr Res Environm Epidemiol, C Doctor Aiguader 88, Barcelona 08003, Spain. EM gcastano@imim.es RI Serra, C/E-6879-2014; Vermeulen, Roel/F-8037-2011; Kogevinas, Manolis/C-3918-2017; OI Serra, C/0000-0001-8337-8356; Vermeulen, Roel/0000-0003-4082-8163; Castano-Vinyals, Gemma/0000-0003-4468-1816; Malats, Nuria/0000-0003-2538-3784 FU Intramural NIH HHS; NCI NIH HHS [N02-CP-11015] NR 26 TC 21 Z9 22 U1 1 U2 12 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JAN PY 2008 VL 65 IS 1 BP 56 EP 60 DI 10.1136/oem.2007.034348 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 242MH UT WOS:000251728700010 PM 17634245 ER PT J AU Deschenes, J Murray, PI Rao, NA Nussenblatt, RB AF Deschenes, Jean Murray, Philip I. Rao, Narsing A. Nussenblatt, Robert B. TI International Uveitis Study Group (IUSG) clinical classification of uveitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE classification; clinical; uveitis ID RETINAL NECROSIS SYNDROME; DIAGNOSTIC-CRITERIA; NOMENCLATURE; DISEASE AB A simplified clinical classification system of uveitis has been proposed by the International Uveitis Study Group. Its aim is to assist in the diagnosis and evaluation of patients with uveitis. Used in conjunction with other recognized classification systems it will also enable enrollment of patients for clinical trials, and contribute to clinical guidelines. C1 [Murray, Philip I.] Univ Birmingham, Birmingham & Midland Eye Ctr, City Hosp, Acad Unit Ophthalmol, Birmingham B18 7QU, W Midlands, England. [Deschenes, Jean] McGill Univ, Montreal, PQ, Canada. [Rao, Narsing A.] Doheny Eye Inst, Los Angeles, CA 90033 USA. [Nussenblatt, Robert B.] NEI, Bethesda, MD 20892 USA. RP Murray, PI (reprint author), Univ Birmingham, Birmingham & Midland Eye Ctr, City Hosp, Acad Unit Ophthalmol, Dudley Rd, Birmingham B18 7QU, W Midlands, England. EM p.i.murray@bham.ac.uk OI Murray, Philip/0000-0001-8491-3795 NR 10 TC 59 Z9 61 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD JAN-APR PY 2008 VL 16 IS 1-2 BP 1 EP 2 DI 10.1080/09273940801899822 PG 2 WC Ophthalmology SC Ophthalmology GA 289OW UT WOS:000255064800001 PM 18379933 ER PT J AU Sen, HN Chan, CC Byrnes, G Fariss, RN Nussenblatt, RB Buggage, RR AF Sen, H. Nida Chan, Chi-Chao Byrnes, Gordon Fariss, Robert N. Nussenblatt, Robert B. Buggage, Ronald R. TI Intravitreal methotrexate resistance in a patient with primary Intraocular lymphoma SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE CNS lymphoma; cytokine; drug resistance; methotrexate; multidrug resistance protein AB Purpose: To describe the clinical course of a patient with multiple recurrences of primary intraocular lymphoma (PIOL). Design: Interventional case report, Methods: Retrospective chart review. Results: A 57-year-old female treated with multiple intravitreal methotrexate injections became refractory to intravitreal methotrexate after a year. Lymphoma cells evaluated using immunocytochemistry and confocal microscopy showed aberrant multidrug resistance-related protein (MRP) and decreased reduced folate carrier (RFC) and folate binding protein (FBP) expression compared to PIOL cells from another patient clinically responsive to methotrexate. Conclusions: This case suggests that alterations in the transport of methotrexate across the cell membrane might contribute to resistance following repeated intravitreal injections. C1 [Sen, H. Nida; Chan, Chi-Chao; Nussenblatt, Robert B.; Buggage, Ronald R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Byrnes, Gordon] Natl Naval Med Ctr, Dept Ophthalmol, Retina Sect, Bethesda, MD USA. [Fariss, Robert N.] NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Sen, HN (reprint author), George Washington Univ, Dept Ophthalmol, 2150 Penn Ave 2A, Washington, DC 20052 USA. EM nidasen@gwu.edu FU Intramural NIH HHS [Z01 EY000222-22] NR 9 TC 13 Z9 14 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD JAN-APR PY 2008 VL 16 IS 1-2 BP 29 EP 33 DI 10.1080/09273940801899764 PG 5 WC Ophthalmology SC Ophthalmology GA 289OW UT WOS:000255064800007 PM 18379939 ER PT J AU John, S Niederhuber, JE AF John, Simone Niederhuber, John E. TI Keeping pace SO ONCOLOGIST LA English DT Editorial Material ID CONTINUING MEDICAL-EDUCATION C1 [Niederhuber, John E.] NCI, Off Director, Bethesda, MD 20892 USA. [John, Simone] NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. RP Niederhuber, JE (reprint author), NCI, Off Director, 31 Ctr Dr,Bldg 31,Room 11A48,MSC 2590, Bethesda, MD 20892 USA. EM niederj@mail.nih.gov NR 5 TC 5 Z9 5 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 1 BP 4 EP 5 DI 10.1634/theoncologist.2007-0213 PG 2 WC Oncology SC Oncology GA 259IT UT WOS:000252933700002 PM 18245007 ER PT J AU Jaffe, CC AF Jaffe, C. Carl TI Response assessment in clinical trials: Implications for sarcoma clinical trial design SO ONCOLOGIST LA English DT Article DE RECIST; response assessment; clinical trial design; imaging response ID SOLID TUMORS; CANCER; MRI AB Response assessment and design of clinical trials require careful consideration of many factors, especially as validated response criteria can ultimately lead to the approval of an anticancer agent. Current anatomic imaging criteria are difficult to apply for evaluation of certain types of tumors, including soft tissue sarcomas. The emergence of new molecular imaging techniques, such as 64-slice computed tomography scanners and dynamic contrast magnetic resonance imaging, provide complementary information to conventional anatomical imaging. Currently the U. S. National Cancer Institute and the U. S. Food and Drug Administration are aiming to revise existing response criteria based on the development of volumetric anatomic imaging for oncology. Reviewing existing and new approaches in the design of clinical trials will help to optimize the clinical development and evaluation of new therapies for sarcomas. C1 NCI, NIH, Div Canc Treatment & Diag, Diagnost Imaging Branch,Canc Imaging Program, Bethesda, MD 20892 USA. RP Jaffe, CC (reprint author), NCI, NIH, Div Canc Treatment & Diag, Diagnost Imaging Branch,Canc Imaging Program, 6116 Execut Blvd, Bethesda, MD 20892 USA. EM jaffec1@mail.nih.gov NR 14 TC 19 Z9 22 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 SU 2 BP 14 EP 18 DI 10.1634/theoncologist.13-S2-14 PG 5 WC Oncology SC Oncology GA 293PS UT WOS:000255347800004 PM 18434633 ER PT J AU Niederhuber, JE AF Niederhuber, John E. TI Tribute to Judah Folkman SO ONCOLOGIST LA English DT Biographical-Item C1 NCI, Bethesda, MD 20892 USA. RP Niederhuber, JE (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 2 BP 210 EP 210 PG 1 WC Oncology SC Oncology GA 268LJ UT WOS:000253581000017 ER PT J AU Fojo, T AF Fojo, Tito TI Commentary: Novel therapies for cancer: Why dirty might be better SO ONCOLOGIST LA English DT Editorial Material DE targeted agents; drug resistance; tyrosine kinase inhibitors; imatinib; Bcr-Abl; c-KIT; epidermal growth factor receptor (EGFR) inhibitors; gefitinib; erlotinib; stem cells ID CHRONIC MYELOID-LEUKEMIA; RENAL-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; BCR-ABL; LUNG-CANCER; IMATINIB MESYLATE; BREAST-CANCER; ACTIVATING MUTATIONS C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Med Oncol Branch, Bldg 10,Room 12N226,9000 Rock Ville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 61 TC 35 Z9 36 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 3 BP 277 EP 283 DI 10.1634/theoncologist.2007-0090 PG 7 WC Oncology SC Oncology GA 285UQ UT WOS:000254802100008 PM 18378537 ER PT J AU Trimble, EL Thompson, S Christian, MC Minasian, L AF Trimble, Edward L. Thompson, Sharon Christian, Michaele C. Minasian, Lori TI Intraperitoneal chemotherapy for women with epithelial ovarian cancer SO ONCOLOGIST LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; INTRAVENOUS CISPLATIN; PHASE-III; CYCLOPHOSPHAMIDE; METAANALYSIS; PACLITAXEL; TRIAL; CARBOPLATIN; MANAGEMENT; CARCINOMA AB In 2006, i.p. chemotherapy re-emerged as a controversial topic in debates about the optimal treatment for women with advanced epithelial ovarian cancer. In this paper, we address the rationale behind i.p. chemotherapy, the data supporting its use, the selection of appropriate patients for i.p. chemotherapy, how best to avoid and manage the toxicities observed with i.p. chemotherapy, and directions for future research. C1 [Trimble, Edward L.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Trimble, Edward L.; Thompson, Sharon] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Trimble, EL (reprint author), NCI, Div Canc Treatment & Diag, 6130 Execut Blvd,Suite 7025,MSC 7436, Bethesda, MD 20892 USA. EM trimblet@ctep.nci.nih.gov NR 26 TC 13 Z9 13 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 4 BP 403 EP 409 DI 10.1634/theoncologist.2007-0058 PG 7 WC Oncology SC Oncology GA 294QU UT WOS:000255421400008 PM 18448554 ER PT J AU Kim, A Fox, E Warren, K Blaney, SM Berg, SL Adamson, PC Libucha, M Byrley, E Balis, FM Widemann, BC AF Kim, AeRang Fox, Elizabeth Warren, Katherine Blaney, Susan M. Berg, Stacey L. Adamson, Peter C. Libucha, Madeleine Byrley, Elena Balis, Frank M. Widemann, Brigitte C. TI Characteristics and outcome of pediatric patients enrolled in phase I oncology trials SO ONCOLOGIST LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 01-05, 2007 CL Chicago, IL SP Amer Soc Clin Oncol DE phase I; pediatric oncology; toxicity; survival ID NATIONAL-CANCER-INSTITUTE; REFRACTORY SOLID TUMORS; BIOAVAILABLE TUBULIN INHIBITOR; TRANS-RETINOIC ACID; CHILDREN; BRANCH; DOCETAXEL; THERAPY; CONDUCT; ABT-751 AB Purpose. To describe the characteristics of pediatric subjects who enroll in phase I trials, to determine the associations between pre-enrollment characteristics and the risk for toxicity, and to analyze response and survival outcomes. Experimental Design. Pre-enrollment characteristics and study outcomes were retrospectively analyzed for children with refractory solid tumors treated in one of 16 phase I trials with similar eligibility criteria at the National Cancer Institute between 1992 and 2005. Results. The 262 subjects analyzed had received a median of two (range, 0 - 9) prior chemotherapy regimens, and were on one (range, 0 - 12) concomitant medication. The Eastern Cooperative Oncology Group performance status scores for subjects were 0 (29%), 1 (48%), and 2 (19%); 19% had received a prior stem cell transplantation and 73% had received prior radiation. Approximately 90% of subjects were evaluable for the primary trial endpoints (toxicity and pharmacokinetics). Seventeen percent of subjects experienced a dose-limiting toxicity (DLT), 5% discontinued the study drug because of toxicity, and a drug-related death occurred in one subject (0.4%). Variables associated with a higher risk for developing a DLT, by multiple logistic regression analysis, were drug dose and prior radiation, for myelosuppressive agents, and drug dose and performance status, for nonmyelosuppressive agents. The complete and partial response rate was 4%; however, 17% of subjects had stable disease ( received three or more cycles). The median overall survival time from the time of enrollment was five months. Conclusions. Primary trial objectives are achieved in approximately 90% of subjects with the standard phase I trial design and eligibility criteria despite the intensification of frontline and salvage therapies in pediatric subjects with cancer. C1 [Kim, AeRang; Fox, Elizabeth; Warren, Katherine; Libucha, Madeleine; Byrley, Elena; Balis, Frank M.; Widemann, Brigitte C.] NCI, Pediatr Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Blaney, Susan M.; Berg, Stacey L.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Kim, A (reprint author), NCI, Pediatr Oncol Branch, Ctr Canc Res, 10 Ctr Dr,Bldg 10-CRC,Room 1-3872, Bethesda, MD 20892 USA. EM kimaer@mail.nih.gov FU Intramural NIH HHS NR 33 TC 17 Z9 17 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 6 BP 679 EP 689 DI 10.1634/theoncologist.2008-0046 PG 11 WC Oncology SC Oncology GA 323FA UT WOS:000257428500007 PM 18586923 ER PT J AU Doroshow, JH AF Doroshow, James H. TI Commentary: Publishing Cancer Clinical Trial Results: A Scientific and Ethical Imperative SO ONCOLOGIST LA English DT Editorial Material DE Cancer clinical trials; Publication bias; Clinical trials database; NCI clinical trials working group C1 [Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Doroshow, James H.] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, NIH, Bldg 31,Room 3A-44,31 Ctr Dr, Bethesda, MD 20892 USA. EM doroshoj@mail.nih.gov NR 9 TC 2 Z9 2 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 9 BP 930 EP 932 DI 10.1634/theoncologist.2008-0168 PG 3 WC Oncology SC Oncology GA 358BZ UT WOS:000259892800004 PM 18794215 ER PT J AU Lacouture, ME Wu, SH Robert, C Atkins, MB Kong, HH Guitart, J Garbe, C Hauschild, A Puzanov, I Alexandrescu, DT Anderson, RT Wood, L Dutcher, JP AF Lacouture, Mario E. Wu, Shenhong Robert, Caroline Atkins, Michael B. Kong, Heidi H. Guitart, Joan Garbe, Claus Hauschild, Axel Puzanov, Igor Alexandrescu, Doru T. Anderson, Roger T. Wood, Laura Dutcher, Janice P. TI Evolving Strategies for the Management of Hand-Foot Skin Reaction Associated with the Multitargeted Kinase Inhibitors Sorafenib and Sunitinib SO ONCOLOGIST LA English DT Article DE Sorafenib; Sunitinib; Hand-foot skin reaction; Forum consensus; Skin ID RENAL-CELL CARCINOMA; QUALITY-OF-LIFE; HEPATOCELLULAR-CARCINOMA; THERAPY; PSORIASIS; CANCER; ERYTHRODYSESTHESIA; ANGIOGENESIS; KERATODERMA; DOXORUBICIN AB The multitargeted kinase inhibitors (MKIs) sorafenib and sunitinib have shown benefit in patients with renal cell carcinoma, hepatocellular carcinoma (sorafenib), and gastrointestinal stromal tumor (sunitinib). Their efficacy in other malignancies is currently being investigated because of their broad range of activity. The effectiveness of these drugs is somewhat diminished by the development of a variety of toxicities, most notably hand-foot skin reaction (HFSR). Although HFSR does not appear to directly affect survival, it can impact quality of life and lead to MKI dose modification or interruption, potentially limiting the antitumor effect. Currently, no standard guidelines exist for the prevention and management of MKI-associated HFSR. To address this issue, an international, interdisciplinary panel of experts gathered in January 2008 to discuss and evaluate the best-practice management of these reactions. Based on these proceedings, recommendations for the management of HFSR have been provided to offer patients the best possible quality of life while taking these drugs and to optimize the patient benefit associated with MKI therapy. The Oncologist 2008; 13: 1001-1011 C1 [Lacouture, Mario E.; Guitart, Joan] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA. [Wu, Shenhong] SUNY Stony Brook, Ctr Canc, Dept Med, Div Med Oncol, Stony Brook, NY 11794 USA. [Robert, Caroline] Inst Gustave Roussy, Dermatol Unit, Villejuif, France. [Atkins, Michael B.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Kong, Heidi H.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Garbe, Claus] Univ Tubingen, Dept Dermatol, Tubingen, Germany. [Hauschild, Axel] Univ Kiel, Dept Dermatol, D-2300 Kiel, Germany. [Puzanov, Igor] Vanderbilt Ingram Canc Ctr, Div Hematol Oncol, Nashville, TN USA. [Anderson, Roger T.] Penn State Coll Med, Hershey, PA USA. [Wood, Laura] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. [Dutcher, Janice P.] New York Med Coll, Ctr Comprehens Canc, Our Lady Mercy Med Ctr, Bronx, NY USA. RP Lacouture, ME (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Dermatol, 676 N St Clair St,Suite 1600, Chicago, IL 60611 USA. EM m-lacouture@northwestern.edu RI Puzanov, Igor/A-7179-2009; Hauschild, Axel/B-3185-2010; OI Kong, Heidi/0000-0003-4424-064X FU Onyx Pharmaceuticals, Inc.; Bayer HealthCare Pharmaceuticals; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois FX The authors take full responsibility for the content of the paper but thank Leslie A. Moody, Ph.D., from the Center for Biomedical Continuing Education, supported by an educational grant from Onyx Pharmaceuticals, Inc., and Bayer HealthCare Pharmaceuticals, for her assistance in organizing the published literature, preparing the initial draft of the manuscript, and collating the comments of the authors. M. E. L. is supported by a Zell Scholarship from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois. NR 57 TC 161 Z9 165 U1 0 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 9 BP 1001 EP 1011 DI 10.1634/theoncologist.2008-0131 PG 11 WC Oncology SC Oncology GA 358BZ UT WOS:000259892800011 PM 18779536 ER PT J AU Stein, WD Figg, WD Dahut, W Stein, AD Hoshen, MB Price, D Bates, SE Fojo, T AF Stein, Wilfred D. Figg, William Doug Dahut, William Stein, Aryeh D. Hoshen, Moshe B. Price, Doug Bates, Susan E. Fojo, Tito TI Tumor Growth Rates Derived from Data for Patients in a Clinical Trial Correlate Strongly with Patient Survival: A Novel Strategy for Evaluation of Clinical Trial Data SO ONCOLOGIST LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; CANCER-SPECIFIC MORTALITY; PHASE-II TRIAL; RADICAL PROSTATECTOMY; RADIATION-THERAPY; DOUBLING TIME; DOCETAXEL; VELOCITY; UTILITY; RISK AB Purpose. The slow progress in developing new cancer therapies can be attributed in part to the long time spent in clinical development. To hasten development, new paradigms especially applicable to patients with metastatic disease are needed. Patients and Methods. We present a new method to predict survival using tumor measurement data gathered while a patient with cancer is receiving therapy in a clinical trial. We developed a two-phase equation to estimate the concomitant rates of tumor regression (regression rate constant d) and tumor growth (growth rate constant g). Results. We evaluated the model against serial levels of prostate-specific antigen (PSA) in 112 patients undergoing treatment for prostate cancer. Survival was strongly correlated with the log of the growth rate constant, log(g) (Pearson r = -0.72) but not with the log of the regression rate constants, log(d) (r = -0.218). Values of log(g) exhibited a bimodal distribution. Patients with log(g) values above the median had a mortality hazard of 5.14 (95% confidence interval, 3.10-8.52) when compared with those with log(g) values below the median. Mathematically, the minimum PSA value (nadir) and the time to this minimum are determined by the kinetic parameters d and g, and can be viewed as surrogates. Conclusions. This mathematical model has applications to many tumor types and may aid in evaluating patient outcomes. Modeling tumor progression using data gathered while patients are on study, may help evaluate the ability of therapies to prolong survival and assist in drug development. The Oncologist 2008; 13: 1046-1054 C1 [Stein, Wilfred D.; Figg, William Doug; Dahut, William; Price, Doug; Bates, Susan E.; Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Stein, Wilfred D.] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel. [Stein, Aryeh D.] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30322 USA. [Hoshen, Moshe B.] Hebrew Univ Jerusalem, Hadassah Sch Publ Hlth, Ein Kerem Med Ctr, Jerusalem, Israel. RP Fojo, T (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov RI Figg Sr, William/M-2411-2016; OI Stein, Aryeh/0000-0003-1138-6458 FU National Cancer Institute FX The authors thank Maha Hussain (University of Michigan Comprehensive Cancer Center, Ann Arbor, MI) and Cathy Tangen (Fred Hutchinson Cancer Center, Seattle, WA) for their kind help and cooperation in providing the data from the Southwest Oncology Group study used to validate the methodology and for reading and commenting on the manuscript.; This work was supported by the intramural program of the National Cancer Institute.; For the convenience of future users of this approach, a file in Excel into which data on tumor sizes at given times can be uploaded and the parameters g and d extracted is available in the Supplementary Material as an Excel File. NR 27 TC 35 Z9 35 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 10 BP 1046 EP 1054 DI 10.1634/theoncologist.2008-0075 PG 9 WC Oncology SC Oncology GA 369VL UT WOS:000260721900004 PM 18838440 ER PT J AU Stein, WD Yang, J Bates, SE Fojo, T AF Stein, Wilfred D. Yang, James Bates, Susan E. Fojo, Tito TI Bevacizumab Reduces the Growth Rate Constants of Renal Carcinomas: A Novel Algorithm Suggests Early Discontinuation of Bevacizumab Resulted in a Lack of Survival Advantage SO ONCOLOGIST LA English DT Article DE Bevacizumab; Chemotherapy efficacy; Clear-cell carcinoma; Drug efficacy; Growth rate constant; Premature discontinuation; RECIST; Renal cell carcinoma; Tumor assessment; Tumor measurements ID CANCER-SPECIFIC MORTALITY; RADIATION-THERAPY; PROSTATE-CANCER; CELL CARCINOMA; RADICAL PROSTATECTOMY; INTERFERON-ALPHA AB Background. To hasten cancer drug development, new paradigms are needed to assess therapeutic efficacy. In a randomized phase II study in patients with renal cell carcinoma, 10 mu g/kg bevacizumab (Avastin (R); Genentech, Inc., South San Francisco, CA) administered every 2 weeks resulted in a longer time to progression but a statistically significant difference in overall survival could not be demonstrated. Methods. We developed a novel two-phase equation to estimate concomitant rates of tumor regression (regression rate constant) and tumor growth (growth rate constant). This method allows us to assess therapeutic efficacy using tumor measurements gathered while a patient receives therapy in a clinical trial. Results. The growth rate constants of renal cell carcinomas were significantly lower during therapy with 10 mu g/kg bevacizumab than those of tumors in patients receiving placebo. In all cohorts the tumor growth rate constants were correlated with survival. That a survival advantage was not demonstrated with bevacizumab appears to have been a result of early discontinuation of bevacizumab. Conclusions. Single-agent bevacizumab significantly affects the growth rate constants of renal cell carcinoma. Extrapolating from the growth rate constants, we conclude that the failure to demonstrate a survival advantage in the original study was a result of premature discontinuation of bevacizumab. The mathematical model described herein has applications to many tumor types and should aid in evaluating the relative efficacies of different therapies. Quantitating tumor growth rate constants using data gathered while patients are enrolled in a clinical trial, as in the present study, may streamline and assist in drug development. The Oncologist 2008; 13: 1055-1062 C1 [Stein, Wilfred D.; Bates, Susan E.; Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Yang, James] NCI, Surg Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Stein, Wilfred D.] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel. RP Fojo, T (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov FU Intramural NIH HHS [Z01 BC010620-04] NR 14 TC 40 Z9 40 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 10 BP 1055 EP 1062 DI 10.1634/theoncologist.2008-0016 PG 8 WC Oncology SC Oncology GA 369VL UT WOS:000260721900005 PM 18827177 ER PT J AU Aragon-Ching, JB Dahut, WL AF Aragon-Ching, Jeanny B. Dahut, William L. TI Osteonecrosis of the Jaw and the Use of Antiangiogenic Agents: Just an Association? SO ONCOLOGIST LA English DT Letter C1 [Aragon-Ching, Jeanny B.] George Washington Univ, Med Ctr, Med Fac Associates, Div Hematol Oncol, Washington, DC 20037 USA. [Dahut, William L.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Aragon-Ching, JB (reprint author), George Washington Univ, Med Ctr, Med Fac Associates, Div Hematol Oncol, 2150 Penn Ave,Suite 3-428, Washington, DC 20037 USA. EM jaragonching@mfa.gwu.edu OI Aragon-Ching, Jeanny/0000-0002-6714-141X NR 6 TC 6 Z9 6 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 12 BP 1314 EP 1314 DI 10.1634/theoncologist.2008-0206 PG 1 WC Oncology SC Oncology GA 388BZ UT WOS:000261996600011 PM 19088325 ER PT J AU Letchoumy, PV Mohan, KVPC Stegeman, JJ Gelboin, HV Hara, Y Nagini, S AF Letchoumy, P. Vidjaya Mohan, K. V. P. Chandra Stegeman, J. J. Gelboin, H. V. Hara, Y. Nagini, S. TI Pretreatment with black tea polyphenols modulates xenobiotic-metabolizing enzymes in an experimental oral carcinogenesis model SO ONCOLOGY RESEARCH LA English DT Article DE black tea polyphenols; chemoprevention; DMBA; hamster buccal pouch carcinogenesis; xenobiotic-metabolizing enzymes; 8-OH-dG ID HAMSTER BUCCAL POUCH; POLYCYCLIC AROMATIC-HYDROCARBONS; LIVER S9 FRACTION; GREEN TEA; CHEMICAL CARCINOGENESIS; BREAST-CANCER; DNA-ADDUCTS; MOUSE-LIVER; IN-VITRO; CYTOCHROME-P450 AB The objective of this study was to evaluate the chemopreventive potential of the black tea polyphenols Polyphenon-B and BTF-35 during the preinitiation phase of 7,12-dimethylbenz[a]anthracene (DMBA)induced hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided into six groups. Animals in groups 2 and 3 received diet containing Polyphenon-B and BTF-35, respectively, 4 weeks before carcinogen administration when they were 6 weeks of age and continued until the final exposure to carcinogen. At 10 weeks of age, animals in groups 1, 2, and 3 were painted with 0.5% DMBA three times a week for 14 weeks. Animals in groups 4 and 5 were given Polyphenon-B and BTF-35 alone, respectively, as in groups 2 and 3. Animals in group 6 served as control. All the animals were sacrificed after an experimental period of 18 weeks. Phase I and phase II xenobiotic-metabolizing enzymes and 8-hydroxy-deoxyguanosine (8-OHdG) in the buccal pouch and liver were used as biomarkers of chemoprevention. Hamsters painted with DMBA showed increased expression of 8-OH-dG and enhanced activities of phase I (CYP450; total as well as CYPIA1, 1A2, and 2B isoforms and cytochrome b5) and phase 11 (GST and quinone reductase) xenobiotic-metabolizing enzymes with increased immunohistochemical expression of CYP1A1, and CYP1B1 isoforms in the buccal pouch. This was accompanied by increased phase I and decreased phase 11 enzyme activities in the liver. Administration of Polyphenon-B and BTF-35 significantly decreased tumor incidence, oxidative DNA damage, phase I enzyme activities as well as expression of CYP1A1 and CYP1B1 isoforms, while enhancing phase II enzyme activities in the buccal pouch and liver. Our results provide a mechanistic basis for the chemopreventive potential of black tea polyphenols. Furthermore, the greater efficacy of BTF-35 in chemoprevention of HBP carcinomas via inhibition of oxidative DNA damage and modulation of xenobiotic-metabolizing enzymes may have a major impact in human oral cancer prevention. C1 [Letchoumy, P. Vidjaya; Mohan, K. V. P. Chandra; Nagini, S.] Annamalai Univ, Fac Sci, Dept Biochem & Biotechnol, Annamalainagar 608002, Tamil Nadu, India. [Stegeman, J. J.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. [Gelboin, H. V.] NCI, Bethesda, MD 20892 USA. [Hara, Y.] Mitsui Norin Co, Shizuoka, Japan. RP Nagini, S (reprint author), Annamalai Univ, Fac Sci, Dept Biochem & Biotechnol, Annamalainagar 608002, Tamil Nadu, India. EM s_nagini@yahoo.com NR 53 TC 12 Z9 12 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0965-0407 EI 1555-3906 J9 ONCOL RES JI Oncol. Res. PY 2008 VL 17 IS 2 BP 75 EP 85 PG 11 WC Oncology SC Oncology GA 302LN UT WOS:000255969900004 ER PT J AU Letchoumy, PV Mohan, KVPC Stegeman, JJ Gelboin, HV Hara, Y Nagini, S AF Letchoumy, P. Vidjaya Mohan, K. V. P. Chandra Stegeman, J. J. Gelboin, H. V. Hara, Y. Nagini, S. TI In Vitro Antioxidative Potential of Lactoferrin and Black Tea Polyphenols and Protective Effects In Vivo on Carcinogen Activation, DNA Damage, Proliferation, Invasion, and Angiogenesis During Experimental Oral Carcinogenesis SO ONCOLOGY RESEARCH LA English DT Article DE Antioxidants; Chemoprevention; Carcinogen activation; Cell proliferation; Angiogenesis ID BUCCAL POUCH CARCINOGENESIS; GREEN TEA; CANCER PREVENTION; BOVINE LACTOFERRIN; GROWTH; CELL; CHEMOPREVENTION; COMBINATION; MECHANISMS; EXPRESSION AB The present study was designed to evaluate the in vitro antioxidant potential of bovine lactoferrin (bLF) and black tea polyphenols [Polyphenon-B (P-B)] as well as in vivo inhibitory effects on the development of 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinomas. Antioxidant activity was screened using a panel of assays including 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS), hydroxyl radical anion (OH center dot), superoxide anion (O-2(center dot-)), and nitric oxide (NO) radical scavenging assays as well as assay for reducing power. The chemopreventive potential of bLF and P-B was assessed in the HBP model based on the modulatory effects on DMBA-induced oxidative DNA damage as well as the expression of proteins associated with carcinogen activation (CYPIAI, CYPIBI), cell proliferation [cyclin Dl, proliferating cell nuclear antigen (PCNA), glutathione S-transferase pi (GST-P)], angiogenesis [vascular endothelial growth factor (VEGF), VEGF receptor I (VEGFRI)], and invasion and metastasis [matrix metalloproteinase-9 (NIMP-9) and tissue inhibitors of MMP-2 (TIMP-2)]. Both bLF and P-B showed high radical scavenging activity and reductive potential. Although administration of bLF and P-B alone suppressed DMBA-induced HBP tumors, combined administration of bLF and P-B was more effective in inhibiting HBP carcinogenesis by inhibiting oxidative DNA damage, carcinogen activation, cell proliferation, invasion, and angiogenesis. Our study suggests that the antioxidative property of bLF and P-B may be responsible for chemoprevention of HBP carcinogenesis by modulating multiple molecular targets. C1 [Letchoumy, P. Vidjaya; Mohan, K. V. P. Chandra; Nagini, S.] Annamalai Univ, Fac Sci, Dept Biochem & Biotechnol, Annamalainagar 608002, Tamil Nadu, India. [Stegeman, J. J.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. [Gelboin, H. V.] NCI, Bethesda, MD 20892 USA. [Hara, Y.] Mitsui Norin Co Ltd, Shizuoka, Japan. RP Nagini, S (reprint author), Annamalai Univ, Fac Sci, Dept Biochem & Biotechnol, Annamalainagar 608002, Tamil Nadu, India. EM s_nagini@yahoo.com FU NIEHS NIH HHS [R01 ES015912] NR 35 TC 19 Z9 20 U1 1 U2 1 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0965-0407 EI 1555-3906 J9 ONCOL RES JI Oncol. Res. PY 2008 VL 17 IS 5 BP 193 EP 203 DI 10.3727/096504008786111365 PG 11 WC Oncology SC Oncology GA 361DG UT WOS:000260107100001 PM 18980016 ER PT J AU Dunleavy, K AF Dunleavy, Kieron TI Angioimmunoblastic T-Cell Lymphoma (AILT): A Unique Clinical and Pathobiological Entity SO ONKOLOGIE LA English DT Editorial Material ID EXPRESSION; AITL C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Dunleavy, K (reprint author), NCI, Ctr Canc Res, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dunleavk@mail.nih.gov NR 11 TC 0 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PY 2008 VL 31 IS 10 BP 509 EP 510 DI 10.1159/000157973 PG 2 GA 362YL UT WOS:000260233000002 PM 18854648 ER PT J AU Sapkota, YD Adhikari, BN Pokharel, GP Poudyal, BK Ellwein, LB AF Sapkota, Yuddha D. Adhikari, Bishwa Nath Pokharel, Gopal P. Poudyal, Bimal K. Ellwein, Leon B. TI The prevalence of visual impairment in school children of upper-middle socioeconomic status in Kathmandu SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article ID REFRACTIVE ERROR; SOUTHERN CHINA; MYOPIA; SCHOOLCHILDREN; POPULATION; DISTRICT; NEPAL; WORK AB Purpose: Assess visual impairment in school children of upper-middle socioeconomic status in Kathmandu for comparison with rural Jhapa District. Methods: Random selection of classes from secondary private schools in Kathmandu was used to identify the study sample. Children in 130 classes at 43 schools were enumerated using school records and examined between January-May 2006. Examinations included visual acuity testing, ocular motility evaluation, cycloplegic refraction, and examination of the external eye, anterior segment, media, and fundus. The principal cause was determined for eyes with uncorrected visual acuity <= 20/40. Results: A total of 4,501 children in grades 5-9 were enumerated; 4282 (95.1%) were examined. The prevalence of uncorrected, presenting, and best-corrected visual impairment (<= 20/40) in the better eye was 18.6%, 9.1%, and 0.86%, respectively. Refractive error was a cause in 93.3% of children with uncorrected visual impairment, amblyopia 1.8%, retinal disorders 1.3%, other causes 0.3%, and unexplained causes 4.4%. Among children correctable in at least one eye, 46.3% presented without the necessary spectacles. Visual impairment with myopia (-0.50 diopters) ranged from 10.9% in 10 year-olds to 27.3% in 15 year-olds, compared to 0.5%-3.0% in rural Jhapa District. Myopic visual impairment was associated with grade level, female gender, parental education, parental spectacle usage, and Mongol ethnicity. Conclusions: Visual impairment with myopia among upper-middle socioeconomic school children in Kathmandu is higher than that in rural Nepal, and a public health problem because nearly half are without corrective spectacles. Effective strategies are needed to eliminate this easily treatable cause of visual impairment. C1 [Ellwein, Leon B.] NEI, NIH, Bethesda, MD 20892 USA. [Sapkota, Yuddha D.; Adhikari, Bishwa Nath; Pokharel, Gopal P.; Poudyal, Bimal K.] Nepal Netra Jyoti Sangh, Kathmandu, Nepal. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. EM ellweinl@nei.nih.gov NR 22 TC 31 Z9 33 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD JAN-FEB PY 2008 VL 15 IS 1 BP 17 EP 23 DI 10.1090/09286590701772011 PG 7 WC Ophthalmology SC Ophthalmology GA 268MN UT WOS:000253584000004 PM 18300085 ER PT J AU Kempen, JH Daniel, E Gangaputra, S Dreger, K Jabs, DA Kacmaz, RO Pujari, SS Anzaar, F Foster, CS Helzlsouer, KJ Levy-Clarke, GA Nussenblatt, RB Llesegang, T Rosenbaum, JT Suhler, EB AF Kempen, John H. Daniel, Ebenezer Gangaputra, Sapna Dreger, Kurt Jabs, Douglas A. Kacmaz, R. Oktay Pujari, Siddharth S. Anzaar, Fahd Foster, C. Stephen Helzlsouer, Kathy J. Levy-Clarke, Grace A. Nussenblatt, Robert B. Llesegang, Teresa Rosenbaum, James T. Suhler, Eric B. TI Methods for identifying long-term adverse effects of treatment in patients with eye diseases: The systemic immunosuppressive therapy for eye diseases (SITE) cohort study SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article ID NATIONAL DEATH INDEX; RHEUMATOID-ARTHRITIS; CARE CENTER; UVEITIS; PATTERNS; EPIDEMIOLOGY; DATABASES; CANCER AB Purpose: To evaluate potential epidemiologic methods for studying long-term effects of immunosuppression on the risk of mortality and fatal malignancy, and present the methodological details of the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study. Methods: Advantages and disadvantages of potential study designs for evaluating rare, late-occurring events are reviewed, and the SITE Cohort Study approach is presented. Results: The randomized, controlled trial is the most robust method for evaluating treatment effects, but long study duration, high costs, and ethical concerns when studying toxicity limit its use in this setting. Retrospective cohort studies are potentially more cost-effective and timely, if records exist providing the desired information over sufficient follow-up time in the past. Case-control methods require extremely large sample sizes to evaluate risk associated with rare exposures, and recall bias is problematic when studying mortality. The SITE Cohort Study is a retrospective cohort study. Past use of antimetabolites, T-cell inhibitors, alkylating agents, and other immuno-suppressives is ascertained from medical records of 9,250 ocular inflammation patients at five tertiary centers over up to 30 years. Mortality and cause-specific mortality outcomes over similar to 100,000 person-years are ascertained using the National Death Index. Immunosuppressed and non-immunosuppressed groups of patients are compared with each other and general population mortality rates from US vital statistics. Calculated detectable differences for mortality/fatal malignancy with respect to the general population are 22%/49% for antimetabolites, 28%/62% for T-cell inhibitors, and 36%/81% for alkylating agents. Conclusions: Information from the SITE Cohort Study should clarify whether use of these immunosuppressive drugs for ocular inflammation increases the risk of mortality and fatal cancer. This epidemiologic approach may be useful for evaluating long-term risks of systemic therapies for other ocular diseases. C1 [Kempen, John H.] Univ Penn, Sch Med, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Daniel, Ebenezer; Gangaputra, Sapna; Dreger, Kurt; Jabs, Douglas A.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Kacmaz, R. Oktay; Pujari, Siddharth S.; Anzaar, Fahd; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Helzlsouer, Kathy J.] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Llesegang, Teresa; Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Div Rheumatol, Portland, OR USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Kempen, JH (reprint author), 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU Intramural NIH HHS; NEI NIH HHS [EY014943, R01 EY014943, R56 EY014943] NR 37 TC 47 Z9 48 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD JAN-FEB PY 2008 VL 15 IS 1 BP 47 EP 55 DI 10.1080/09286580701585892 PG 9 WC Ophthalmology SC Ophthalmology GA 268MN UT WOS:000253584000008 PM 18300089 ER PT J AU Salomao, SR Cinoto, RW Berezovsky, A Araujo-Filho, A Mitsuhiro, MRKH Mendieta, L Morales, PHA Pokharel, GP Belfort, R Ellwein, LB AF Salomao, Solange R. Cinoto, Rafael W. Berezovsky, Adriana Araujo-Filho, Arnaud Mitsuhiro, Marcia R. K. H. Mendieta, Luana Morales, Paulo H. A. Pokharel, Gopal P. Belfort, Rubens Ellwein, Leon B. TI Prevalence and causes of vision impairment and blindness in older adults in Brazil: The Sao Paulo eye study SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE adults; prevalence; vision impairment; blindness; low-income ID CATARACT-SURGERY; VISUAL IMPAIRMENT; DISTRICT; COUNTY; CHINA AB Purpose: Investigate prevalence and causes of vision impairment/blindness in older adults in a low-middle income area of Sao Paulo, Brazil. Methods: Cluster sampling, based on geographically defined census sectors, was used in randomly selecting cross-sectionally persons 50 years of age or older. Subjects were enumerated through a door-to-door survey and invited for measurement of presenting and best-corrected visual acuity and an ocular examination. The principal cause was identified for eyes with presenting visual acuity less than 20/32. Results: A total of 4,224 eligible persons in 2,870 households were enumerated, and 3,678 (87.1%) examined. The prevalence of presenting visual acuity 20/32 in both eyes was 61.6% (95% confidence interval [CI]: 59.4%-63.9%), and 80.4% (95% CI: 78.8%-82.1%) with best correction. The prevalence of visual impairment ( 20/63 to 20/200) in the better eye was 4.74% (95% CI: 3.97%-5.53%), and 2.00% (95% CI: 1.52%-2.49%) with best correction. The prevalence of presenting bilateral blindness ( 20/200) was 1.51% (95% CI: 1.20%-1.82%), and 1.07% (95% CI: 0.79%-1.35%) with best correction. Presenting blindness was associated with older age and lack of schooling. Retinal disorders (35.3%) and cataract (28.3%) were the most common causes of blind eyes. Cataract (33.2%), refractive error (32.3%), and retinal disorders (20.3%) were the main causes of vision impairment 20/63 to 20/200, with refractive error (76.8%) and cataract (12.2%) as main causes for eyes with acuity 20/32 to 20/63. Conclusions: Vision impairment is a significant problem in older Brazilians reinforcing the need to implement prevention of blindness programs for elderly people with emphasis on those without schooling. C1 [Salomao, Solange R.; Cinoto, Rafael W.; Berezovsky, Adriana; Araujo-Filho, Arnaud; Mitsuhiro, Marcia R. K. H.; Mendieta, Luana; Morales, Paulo H. A.; Belfort, Rubens] Univ Fed Sao Paulo, Dept Ophthalmol, Vis Inst, UNIFESP Paulista Sch Med, BR-04023062 Sao Paulo, Brazil. [Pokharel, Gopal P.] Nepal Netra Jyoti Singh, Kathmandu, Nepal. [Ellwein, Leon B.] NEI, NIH, Bethesda, MD 20892 USA. RP Salomao, SR (reprint author), Univ Fed Sao Paulo, Dept Ophthalmol, Vis Inst, UNIFESP Paulista Sch Med, Rua Botucatu 862, BR-04023062 Sao Paulo, Brazil. EM ssalomao@oftalmo.epm.br RI Salomao, Solange/G-9500-2012; Belfort Jr, Rubens/E-2252-2012; Berezovsky, Adriana/F-2341-2013; Mitsuhiro, Marcia/H-7872-2013 OI Salomao, Solange/0000-0002-3436-5599; Belfort Jr, Rubens/0000-0002-8422-3898; FU NEI NIH HHS [N01-EY-2103] NR 15 TC 14 Z9 16 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PY 2008 VL 15 IS 3 BP 167 EP 175 DI 10.1080/09286580701843812 PG 9 WC Ophthalmology SC Ophthalmology GA 318CN UT WOS:000257069300006 PM 18569812 ER PT J AU Bonilha, VL Trzupek, KM Li, Y Francis, PJ Holly, JG Rayborn, ME Smaoui, N Weleber, RG AF Bonilha, Vera L. Trzupek, Karmen M. Li, Yong Francis, Peter J. Holly, Joe G. Rayborn, Mary E. Smaoui, Nizar Weleber, Richard G. TI Choroideremia: Analysis of the retina from a female symptomatic carrier SO OPHTHALMIC GENETICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 06-10, 2007 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol DE choroideremia; carrier state; immunohistochemistry; cone opsins; rhodopsin ID 3 CONE CLASSES; DEGENERATION; GENE; PHOTORECEPTORS; ARRANGEMENT; PIGMENT; MODEL; CHM; EYE AB Purpose: To define the retinal pathology in a 91 year-old affected matriarch of a three-generation choroideremia family with multiple manifesting carriers. Methods: Tissue from three different retinal areas was processed for immunohistochemistry. The macular area was processed for transmission electron microscopy. Cryosections were studied by indirect immunofluorescence, using well-characterized antibodies to cone cytoplasm, rhodopsin and cone opsins. The affected donor eyes were compared to a postmortem matched normal eye. Results: The retina displayed areas of severe degeneration, with no photoreceptor outer segments, photoreceptor nuclear atrophy, and atrophy of the inner retina. Other retinal areas were near to normal. The RPE was severely degenerated, with thinning, pigment clumping and sub-epithelial debris deposition in all the areas examined. The choroid displayed depigmentation. Labeling with cone opsin antibodies revealed that cones were drastically affected: blue opsin was almost completely absent, while red/green opsins were distributed along the entire plasma membrane of the cell. Rhodopsin was also distributed along the entire rod plasma membrane. Ultrastructural analysis of the affected macula revealed the absence of RPE apical microvilli and basal infoldings. Instead, RPE's basal surface and choroid displayed the presence of banded fibers composed of clumps of wide-spacing collagen. Bruch's membrane was filled with vesicular structures, some smooth and others with bristle-like projections. Conclusions: The histological data suggests that the clinical manifestation in this donor is related to degenerative changes in the retina, RPE, and choroid. C1 [Bonilha, Vera L.; Li, Yong; Holly, Joe G.; Rayborn, Mary E.] Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. [Trzupek, Karmen M.; Francis, Peter J.; Weleber, Richard G.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. [Smaoui, Nizar] NIH, NEI DNA Diagnost Lab, Bethesda, MD 20892 USA. RP Bonilha, VL (reprint author), Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave,I31, Cleveland, OH 44195 USA. EM bonilhav@ccf.org FU NEI NIH HHS [EY015638, R24 EY015638] NR 27 TC 16 Z9 18 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1381-6810 J9 OPHTHALMIC GENET JI Ophthalmic Genet. PY 2008 VL 29 IS 3 BP 99 EP 110 DI 10.1080/13816810802206499 PG 12 WC Genetics & Heredity; Ophthalmology SC Genetics & Heredity; Ophthalmology GA 344DI UT WOS:000258905600003 PM 18766988 ER PT J AU Chan, CC Ross, RJ Shen, DF Ding, XY Majumdar, Z Bojanowski, CM Zhou, M Salem, N Bonner, R Tuo, JS AF Chan, Chi-Chao Ross, Robert J. Shen, Defen Ding, Xiaoyan Majumdar, Zigurts Bojanowski, Christine M. Zhou, Min Salem, Norman, Jr. Bonner, Robert Tuo, Jingsheng TI Ccl2/Cx3cr1-deficient mice: An animal model for age-related macular degeneration SO OPHTHALMIC RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Animal Models of Ocular Inflammation CY SEP, 2007 CL Paris, FRANCE SP Int Ocular Inflammat Soc DE age-related macular degeneration; animal model; CCL2; CX3CR1; retinal pigment epithelium; N-retinylidene-N-retinylethanolamine; chaperone; omega-3 long-chain polyunsaturated fatty acids ID DOCOSAHEXAENOIC ACID; PROTEIN; RETINA; STRESS; ERP29 AB Background/Aims: Senescent Ccl2(-/-) mice develop cardinal features of human age-related macular degeneration (AMD). Loss-of-function single-nucleotide polymorphisms within CX3CR1 are associated with AMD. Methods: We generated Ccl2(-/-)/Cx3cr1(-/-) [double-knockout (DKO)] mice and evaluated the eyes using fundoscopy routine histology, immunochemistry, biochemistry and proteomics. Results: At 6 weeks old, all DKO mice developed AMD-like retinal lesions such as abnormal retinal pigment epithelium cells, drusen, photoreceptor atrophy and choroidal neovascularization, which progressed with age and reversed with high omega-3 long-chain polyunsaturated fatty acid diet. N-retinylidene-N-retinylethanolamine (A2E), a major lipofuscin fluorophore, illustrated by an emission peak at similar to 600 nm, was significantly higher in DKO retinal pigment epithelium. Decreased ERp29 was found in the retina of DKO mice. Conclusion: A broad spectrum of AMD pathologies with early onset and high penetrance in these mice implicate certain chemokines, A2E and endoplasmic reticulum proteins in AMD pathogenesis. Copyright (c) 2008 S. Karger AG, Basel. C1 [Chan, Chi-Chao; Ross, Robert J.; Shen, Defen; Ding, Xiaoyan; Bojanowski, Christine M.; Zhou, Min; Tuo, Jingsheng] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Majumdar, Zigurts; Bonner, Robert] NICHHD, Sect Med Biophys, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. [Salem, Norman, Jr.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov RI Bonner, Robert/C-6783-2015; OI Tuo, Jingsheng/0000-0002-1372-7810 FU Intramural NIH HHS [Z01 EY000418-04] NR 24 TC 57 Z9 60 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHAL RES JI Ophthalmic Res. PY 2008 VL 40 IS 3-4 BP 124 EP 128 DI 10.1159/000119862 PG 5 WC Ophthalmology SC Ophthalmology GA 289UK UT WOS:000255079200004 PM 18421225 ER PT J AU Caspi, RR Silver, PB Luger, D Tang, J Cortes, LM Pennesi, G Mattapallil, MJ Chan, CC AF Caspi, Rachel R. Silver, Phyllis B. Luger, Dror Tang, Jun Cortes, Lizette M. Pennesi, Giuseppina Mattapallil, Mary J. Chan, Chi-Chao TI Mouse models of experimental autoimmune uveitis SO OPHTHALMIC RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Animal Models of Ocular Inflammation CY SEP, 2007 CL Paris, FRANCE SP Int Ocular Inflammat Soc DE uveitis, mouse; uveoretinitis; autoimmune disease; Th1; Th17 ID RETINOID-BINDING PROTEIN; II TRANSGENIC MICE; UVEORETINITIS EAU; ANTIGENS; DISEASE; CELLS; IDENTIFICATION; RESPONSES; THYMUS; IRBP AB The mouse model of experimental autoimmune uveitis, induced by immunization of mice with the retinal protein IRBP, was developed in our laboratory 20 years ago and published in 1988. Since that time it has been adopted by many investigators and has given rise to many studies that helped elucidate genetic influences, dissect the basic mechanisms of pathogenesis and test novel immunotherapeutic paradigms. The current overview will summarize the salient features of the experimental autoimmune uveitis model and discuss its mechanisms. Copyright (c) 2008 S. Karger AG, Basel. C1 [Caspi, Rachel R.; Silver, Phyllis B.; Luger, Dror; Tang, Jun; Cortes, Lizette M.; Pennesi, Giuseppina; Mattapallil, Mary J.; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N222, Bethesda, MD 20892 USA. OI Caspi, Rachel/0000-0002-7140-7671 FU Intramural NIH HHS [Z01 EY000222-22] NR 23 TC 36 Z9 38 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHAL RES JI Ophthalmic Res. PY 2008 VL 40 IS 3-4 BP 169 EP 174 DI 10.1159/000119871 PG 6 WC Ophthalmology SC Ophthalmology GA 289UK UT WOS:000255079200013 PM 18421234 ER PT J AU Fujimoto, C Shi, GP Gery, I AF Fujimoto, Chiaki Shi, Guangpu Gery, Igal TI Microbial products trigger autoimmune ocular inflammation SO OPHTHALMIC RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Animal Models of Ocular Inflammation CY SEP, 2007 CL Paris, FRANCE SP Int Ocular Inflammat Soc DE ocular inflammation; autoimmunity; microbial products; Toll-like receptors; Toll-like receptor ligands; cytokines; pertussis toxin ID MOLECULAR MIMICRY; T-CELLS; UVEITOPATHOGENIC SITE; SELF-TOLERANCE; S-ANTIGEN; INDUCTION; DISEASE; UVEITIS; RECOGNITION; LYMPHOCYTES AB Purpose: Microbial products stimulate the immune system by interacting with Toll-like receptors (TLR) on antigen-presenting cells. This study examined the hypothesis that microbial products, which function as TLR ligands, are playing a major role in triggering pathogenic autoimmunity. Methods: An experimental system was developed in which microbial TLR ligands were tested in vivo for their capacity to stimulate naive CD4 cells specific against hen egg lysozyme (HEL) to become effector cells capable of inducing inflammation in eyes in which HEL is expressed. The ligands' mode of action was analyzed by determining their effects on the proliferation, acquisition of tissue-invading capacity, i.e. elevated CD49d and decreased CD62L expression, and production of interferon-gamma by the HEL-specific cells. Results: All the 7 tested TLR ligands triggered ocular inflammation in the experimental system used here, with pertussis toxin surpassing all other ligands in its activities. A correlation was found between the capacity of the ligands to trigger pathogenic immunity and to stimulate the proliferation, modification of cell surface and interferon-gamma production by T cells. Conclusions: This study provides direct evidence to support the notion that microbial products are capable of triggering pathogenic autoimmunity. Copyright (c) 2008 S. Karger AG, Basel. C1 [Fujimoto, Chiaki; Shi, Guangpu; Gery, Igal] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N 112, Bethesda, MD 20892 USA. EM geryi@nei.nih.gov FU Intramural NIH HHS [Z01 EY000069-30] NR 24 TC 5 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHAL RES JI Ophthalmic Res. PY 2008 VL 40 IS 3-4 BP 193 EP 199 DI 10.1159/000119875 PG 7 WC Ophthalmology SC Ophthalmology GA 289UK UT WOS:000255079200017 PM 18421238 ER PT J AU Wong, WT Agron, E Coleman, HR Tran, T Reed, GF Csaky, K Chew, EY AF Wong, Wai T. Agron, Elvira Coleman, Hanna R. Tran, Tam Reed, George F. Csaky, Karl Chew, Emily Y. TI Clinical characterization of retinal capillary hemangioblastomas in a large population of patients with von Hippel-Lindau disease SO OPHTHALMOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; MUTATION; CANCER AB Objective: To report the epidemiology and ocular phenotype of retinal capillary hemangioblastomas associated with von Hippel-Lindau (VHL) disease in a large cohort of patients and to correlate patient and ocular characteristics to visual morbidity in this population. Design: Cross-sectional study. Participants: In 220 unrelated pedigrees, 335 patients affected with VHL disease and retinal capillary hemangioblastomas (RCHs) in at least 1 eye. Methods: Demographics of the patient population were recorded and the ocular phenotype of each patient was obtained with a comprehensive ocular examination. Main Outcome Measures: The patient population was characterized and the ocular phenotype described in relationship to tumor location, number, and extent of retinal involvement. Correlations between patient demographics, ocular phenotype, and visual function were analyzed. Results: We detected RCHs unilaterally in 42.1 % and bilaterally in 57.9% of patients. No correlation was detected between the age, gender, or laterality of involvement. Of involved eyes, 86.6% had tumors that could be individually visualized; of these, tumors were commonly found in the peripheral retina (84.7%) only, and less commonly in the juxtapapillary area (15.3%). The tumor count in the periphery averaged 2.5 +/- 1.8 per eye, with 25.2% of eyes having >1 quadrant of retinal involvement. Of involved eyes, 13.4% were enucleated or prephthsical; approximately 1 in 5 patients had :l eyes so affected. Severe visual impairment (visual acuity :<=;20/160) in affected eyes were more likely to be associated with increasing age, the presence of juxtapapillary lesions, and an increasing number and extent of peripheral lesions. Conclusions: This large cohort of VHL patients with RCHs has enabled a systematic and quantitative characterization of the demographics, ocular features, and visual function in VHL disease. Clinical correlations between the visual morbidity and ocular features of the disease were also performed, producing measures that can help clinicians to estimate visual prognoses better based on the ocular phenotype of the disease. Ophthalmology 2008; 115:181-188 (c) 2008 by the American Academy of Ophthalmology. C1 [Wong, Wai T.; Agron, Elvira; Coleman, Hanna R.; Tran, Tam; Reed, George F.; Csaky, Karl; Chew, Emily Y.] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Res, NIH, 10 Ctr Dr MSC 1204,10 CRC,Room 3-2531, Bethesda, MD 20892 USA. RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU Intramural NIH HHS [Z99 EY999999] NR 14 TC 27 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2008 VL 115 IS 1 BP 181 EP 188 DI 10.1016/j.ophtha.2007.03.009 PG 8 WC Ophthalmology SC Ophthalmology GA 248FK UT WOS:000252137300027 PM 17543389 ER PT J AU Modi, AA Liang, TJ AF Modi, A. A. Liang, T. J. TI Hepatitis C: a clinical review SO ORAL DISEASES LA English DT Review DE natural history; therapy; genotype; peginterferon; ribavirin ID COMBINATION THERAPY; VIRAL CLEARANCE; VIRUS-INFECTION; PLUS RIBAVIRIN; UNITED-STATES; PEGINTERFERON; MANAGEMENT; CIRRHOSIS; INTERFERON-ALPHA-2B; HISTORY AB Hepatitis C is a major cause of chronic liver disease. It has been recognized as a global health problem because of the progression to cirrhosis and hepatocellular cancer. Chronic hepatitis C is usually asymptomatic but can cause considerable liver damage before its recognition. This review discusses the natural history, clinical features, diagnosis, therapy, treatment responses and the side effects associated with the treatment of hepatitis C. C1 [Modi, A. A.; Liang, T. J.] NIDDK, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDK, Natl Inst Hlth, 10 Ctr Dr,Room 9B-16, Bethesda, MD 20892 USA. EM Jakel@bdg10.niddk.nih.gov FU Intramural NIH HHS [Z01 DK054503-12, Z01 DK054505-12, Z01 DK054511-02, Z99 DK999999, ZIA DK054505-13, ZIA DK054511-03, Z01 DK054504-12, ZIA DK054504-13] NR 34 TC 30 Z9 35 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1354-523X J9 ORAL DIS JI Oral Dis. PD JAN PY 2008 VL 14 IS 1 BP 10 EP 14 DI 10.1111/j.1601-0825.2007.01419.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 243AD UT WOS:000251766400003 PM 18173443 ER PT J AU Domingo, DL Freeman, AF Davis, J Puck, JM Tianxia, W Holland, SM Hart, TC AF Domingo, D. L. Freeman, A. F. Davis, J. Puck, J. M. Tianxia, W. Holland, S. M. Hart, T. C. TI Novel intraoral phenotypes in hyperimmunoglobulin-E syndrome SO ORAL DISEASES LA English DT Article DE hyper-IgE; immunodeficiency; mucosa; gingiva; dentition ID HYPER-IGE SYNDROME; PREVALENCE; CHILDREN; TONGUE AB AIM: Hyperimmunoglobulin-E syndrome (HIES) is a primary immunodeficiency characterized by eczema, recurrent skin and lung infections with pneumatocoele formation, and extremely elevated serum immunoglobulin-E. The precise immunologic defect and genetic etiology remain unknown. Non-immunologic findings include characteristic facial features (prominent forehead, fleshy nasal tip, and increased interalar distance); skeletal involvement (pathological fractures, scoliosis, and craniosynostosis); and retention of primary teeth. This study aims to characterize intraoral soft tissue findings in HIES patients. METHODS: Sixty HIES patients (4-54 years, 27 males, 33 females) received intraoral and radiographic evaluations. Chronological dental development was also assessed. RESULTS: Lesions of the hard palate and dorsal tongue were found in 55% and 60% of patients, respectively. Palatal lesions ranged from a generalized surface keratosis to a midline sagittal fibrotic bridge. Tongue lesions consisted of multiple fissures and a midline cleft. On the lip and buccal mucosa, keratotic plaques and/or surface fissures were found in 8% and 23% of patients, respectively. Manifested in 76.7% of patients, the intraoral lesions were significantly more prevalent than the characteristic facial traits (P = 0.0013). CONCLUSIONS: Alterations in oral mucosa and gingiva were present in the majority of HIES patients. These novel intraoral findings may facilitate the diagnosis of HIES. C1 [Domingo, D. L.; Tianxia, W.; Hart, T. C.] Natl Inst Dent & Craniofacial Res, Clin Res Core, Natl Inst Hlth, Bethesda, MD 20892 USA. [Freeman, A. F.] NIAID, Bethesda, MD 20892 USA. [Davis, J.; Puck, J. M.] NHGRI, Bethesda, MD 20892 USA. RP Domingo, DL (reprint author), Natl Inst Dent & Craniofacial Res, Clin Res Core, Natl Inst Hlth, 10 Ctr Dr,Bldg 10,Room 1N-117 MSC 1191, Bethesda, MD 20892 USA. EM ddomingo@mail.nih.gov FU Intramural NIH HHS NR 13 TC 12 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1354-523X J9 ORAL DIS JI Oral Dis. PD JAN PY 2008 VL 14 IS 1 BP 73 EP 81 DI 10.1111/j.1601-0825.2007.01363.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 243AD UT WOS:000251766400012 PM 18173452 ER PT J AU Lucas-Lopez, C Allingham, JS Lebl, T Lawson, CPAT Brenk, R Sellers, JR Rayment, I Westwood, NJ AF Lucas-Lopez, Cristina Allingham, John S. Lebl, Tomas Lawson, Christopher P. A. T. Brenk, Ruth Sellers, James R. Rayment, Ivan Westwood, Nicholas J. TI The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID BLEBBISTATIN INHIBITION; MOTOR DOMAIN; CONTRACTILE RING; II INHIBITOR; CYTOKINESIS; MECHANISM; CELLS; SPECIFICITY; KINASE; ACTIN AB The small molecule blebbistatin is now a front line tool in the study of myosin function. Chemical modi. cation of the tricyclic core of blebbistatin could deliver the next generation of myosin inhibitors and to help address this we report here on the impact of structural changes in the methyl-substituted aromatic ring of blebbistatin on its biological activity. Chemical methods for the preparation of isomeric methyl-containing analogues are reported and a series of co-crystal structures are used to rationalise the observed variations in their biological activity. These studies further support the view that the previously identified binding mode of blebbistatin to Dictyostelium discoideum myosin II is of relevance to its mode of action. A discussion of the role that these observations have on planning the synthesis of focused libraries of blebbistatin analogues is also provided including an assessment of possibilities by computational methods. These studies are ultimately directed at the development of novel myosin inhibitors with improved affinity and different selectivity profiles from blebbistatin itself. C1 [Lucas-Lopez, Cristina; Lebl, Tomas; Lawson, Christopher P. A. T.; Westwood, Nicholas J.] Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland. [Lucas-Lopez, Cristina; Lebl, Tomas; Lawson, Christopher P. A. T.; Westwood, Nicholas J.] Univ St Andrews, Ctr Biomol Sci, St Andrews KY16 9ST, Fife, Scotland. [Allingham, John S.; Rayment, Ivan] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. [Brenk, Ruth] Univ Dundee, Div Biol Chem & Drug Discovery, Coll Life Sci, Dundee DD1 5EH, Scotland. [Sellers, James R.] NHLBI, Lab Mol Physiol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Westwood, NJ (reprint author), Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland. EM njw3@st-andrews.ac.uk RI Lawson, Christopher/M-6010-2016; OI Lawson, Christopher/0000-0002-0729-182X; rayment, ivan/0000-0001-9279-7835; Brenk, Ruth/0000-0002-6204-5488 FU Biotechnology and Biological Sciences Research Council; NIAMS NIH HHS [AR35186, R01 AR035186] NR 33 TC 12 Z9 12 U1 1 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2008 VL 6 IS 12 BP 2076 EP 2084 DI 10.1039/b801223g PG 9 WC Chemistry, Organic SC Chemistry GA 309QP UT WOS:000256475600008 PM 18528569 ER PT J AU Li, H Miller, PS Seidman, MM AF Li, Hong Miller, Paul S. Seidman, Michael M. TI Selectivity and affinity of DNA triplex forming oligonucleotides containing the nucleoside analogues 2 '-O-methyl-5-(3-amino-1-propynyl)uridine and 2 '-O-methyl-5-propynyluridine SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID TARGETED GENE KNOCKOUT; DOUBLE-STRANDED DNA; 3RD STRAND; 2'-AMINOETHOXY-MODIFIED OLIGONUCLEOTIDES; 2'-O-(2-AMINOETHYL) RESIDUES; DUAL RECOGNITION; HELIX FORMATION; BASE-PAIRS; STABILITY; SEQUENCE AB Triplex forming oligonucleotides (TFOs) containing the nucleoside analogues 2'-O-methyl-5-propynyluridine (1) and 2'-O-methyl-5-(3-amino-1-propynyl) uridine (2) were synthesized. The affinity and selectivity of triplex formation by these TFOs were studied by gel shift analysis, T(m) value measurement, and association rate assays. The results show that the introduction of 1 and 2 into TFOs can improve the stability of the triplexes under physiological conditions. Optimized distribution of 1 or 2 in the TFOs combined with a cluster of contiguous nucleosides with 2'-aminoethoxy sugars resulted in formation of triplexes with further enhanced stability and improved selectivity. C1 [Li, Hong; Seidman, Michael M.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Miller, Paul S.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA. RP Seidman, MM (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM pmiller@jhsph.edu; seid-manm@grc.nia.nih.gov FU Intramural Research Program of the NIH; National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 30 TC 6 Z9 6 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2008 VL 6 IS 22 BP 4212 EP 4217 DI 10.1039/b810709b PG 6 WC Chemistry, Organic SC Chemistry GA 384KW UT WOS:000261744700019 PM 18972052 ER PT J AU Kelly, MH Brillante, B Collins, MT AF Kelly, M. H. Brillante, B. Collins, M. T. TI Pain in fibrous dysplasia of bone: age-related changes and the anatomical distribution of skeletal lesions SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE analgesia; biophosphonates; fibrous dysplasia; Gs alpha; McCune-Albright syndrome; pain ID MCCUNE-ALBRIGHT-SYNDROME; STIMULATORY G-PROTEIN; PAMIDRONATE TREATMENT; INTRAVENOUS PAMIDRONATE; CHILDREN; DYSFUNCTION; MUTATIONS; GENE; HYPERTHYROIDISM; ABNORMALITIES AB To determine the prevalence, distribution, age-related changes and treatment of pain in fibrous dysplasia, we studied 78 children and adults. Pain was common, more prevalent and intense in adults, sometimes requiring narcotic analgesia. It was often untreated, especially in children, and surprisingly severity did not correlate with skeletal disease burden. Introduction Pain is common in fibrous dysplasia (FD), but relatively unstudied. We studied a well-characterized population of patients with a spectrum of disease. Methods Thirty-five children (16 male, 19 female, mean age 11.4 (range 5-18)) and 43 adults (15 male, 28 female, 23-62 yrs, mean age 40.3 (range 23-62)) were studied. Bone scans were used to identify the location and extent of disease. The Brief Pain Inventory was used to determine severity. Results Pain at sites of FD was common, reported by 67% of the population, but more prevalent and severe in the adult group than the children (81% and 49%, respectively p < 0.005, severity 4.1/10, and 2.8/10, respectively, p < 0.01). Surprisingly, there was no correlation between pain severity and skeletal disease burden. Children were more likely than adults to be untreated for pain (44% vs. 26%). Conclusions Pain, which was sometimes severe, was common in subjects with FD. It was often un- or under-treated, especially in children. The prevalence and severity of pain was greater in the adult group, but unrelated to the burden of FD. C1 NIDCR, Skeletal Clin Studies Unit, CSDB, NIH, Bethesda, MD 20892 USA. RP Collins, MT (reprint author), NIDCR, Skeletal Clin Studies Unit, CSDB, NIH, Bldg 30 Room 228 MSC 4320, Bethesda, MD 20892 USA. EM mc247k@nih.gov FU Intramural NIH HHS NR 40 TC 23 Z9 26 U1 0 U2 3 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JAN PY 2008 VL 19 IS 1 BP 57 EP 63 DI 10.1007/s00198-007-0425-x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 236RS UT WOS:000251321700007 PM 17622477 ER PT J AU Zhu, W Robey, PG Boskey, AL AF Zhu, Wei Robey, Pamela Gehron Boskey, Adele L. BE Marcus, R Feldman, D Nelson, DA Rosen, CJ TI The Regulatory Role of Matrix Proteins in Mineralization of Bone SO OSTEOPOROSIS, VOLS I AND II, 3RD EDITION LA English DT Article; Book Chapter ID OSTEOBLAST-LIKE CELLS; ALKALINE-PHOSPHATASE GENE; GAMMA-CARBOXYGLUTAMIC ACID; RAT OSTEOCALCIN GENE; GROWTH-FACTOR-BETA; HUMAN FIBRONECTIN GENE; HUMAN ALPHA-2-HS GLYCOPROTEIN; PRO-ALPHA-1(I) COLLAGEN GENE; KERATAN SULFATE PROTEOGLYCAN; MESSENGER-RNA EXPRESSION C1 [Zhu, Wei] Hosp Special Surg, New York, NY 10021 USA. [Robey, Pamela Gehron] NIDR, Bone Res Branch, NIH, Bethesda, MD 20892 USA. [Boskey, Adele L.] Cornell Univ, Hosp Special Surg, Weill Med Coll, New York, NY 10021 USA. RP Zhu, W (reprint author), Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. OI Boskey, Adele/0000-0002-6181-2219 NR 623 TC 6 Z9 7 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-055347-4 PY 2008 BP 191 EP 240 PG 50 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BDH03 UT WOS:000313195400010 ER PT J AU McGowan, JA Stefanick, ML AF McGowan, Joan A. Stefanick, Marcia L. BE Marcus, R Feldman, D Nelson, DA Rosen, CJ TI Estrogen Therapy: Prevention and Treatment of Osteoporosis SO OSTEOPOROSIS, VOLS I AND II, 3RD EDITION LA English DT Article; Book Chapter ID HORMONE REPLACEMENT THERAPY; BONE-MINERAL DENSITY; EARLY POSTMENOPAUSAL WOMEN; INTERVENTIONS PEPI TRIAL; CORONARY-HEART-DISEASE; INITIATIVE RANDOMIZED-TRIAL; SEX STEROID-LEVELS; HIP FRACTURE; BIOCHEMICAL MARKERS; ELDERLY-WOMEN C1 [McGowan, Joan A.] NIAMS, Musculoskeletal Dis Branch, NIH, DHHS, Bethesda, MD USA. [Stefanick, Marcia L.] Stanford Univ, Stanford, CA 94305 USA. [Stefanick, Marcia L.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. RP McGowan, JA (reprint author), NIAMS, Musculoskeletal Dis Branch, NIH, DHHS, Bethesda, MD USA. NR 109 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-055347-4 PY 2008 BP 1687 EP 1703 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BDH03 UT WOS:000313195400073 ER PT J AU Falanga, V Brem, H Ennis, WJ Wolcott, R Gould, LJ Ayello, EA AF Falanga, Vincent Brem, Harold Ennis, William J. Wolcott, Randall Gould, Lisa J. Ayello, Elizabeth A. TI Maintenance debridement in the treatment of difficult-to-heal chronic wounds SO OSTOMY WOUND MANAGEMENT LA English DT Article ID QUALITY-OF-LIFE; VENOUS LEG ULCERS; BED PREPARATION; TISSUE INHIBITOR; PRESSURE ULCERS; DIABETIC FOOT; GUIDELINES; EXPRESSION; BIOFILMS; FIBROBLASTS AB Introduction: Maintenance debridement has been proposed as a therapeutic intervention to address the problem of chronic wounds characterized by an adequate wound bed but absent or slow healing. A panel of experts convened to address the rationale and method of maintenance debridement. Purpose: The goals of the panel were to summarize the scientific rationale for maintenance debridement, discuss the biochemical and cellular abnormalities in the wound bed, and provide a working algorithm for how maintenance debridement should be used. Methods: A multidisciplinary panel of wound healing and wound care exerts comprising the fields of nursing, dermatology, internal medicine, and surgery was assembled to address maintenance debridement from different points of view and offer a unified approach. Findings: The chronic wound contains a number of microbial, biochemical, and cellular features and abnormalities that prevent or slow its progression to healing despite a seemingly adequate wound bed. Under these circumstances, maintenance debridement is proposed as a way to remove tissues that colonized with an excessive bacterial burden and diminish what can be described as a biochemical and cellular burden that impairs healing. A working clinical algorithm is proposed. Conclusion: Maintenance debridement is a proactive way to "jump-start" the wound arid keep it in a healing mode, even when traditional debridement may not appear necessary because of a seemingly "healthy" wound bed. C1 [Falanga, Vincent] Roger Williams Med Ctr, Dept Dermatol, NIH Ctr Biomed Res Excellence, Providence, RI 02908 USA. [Falanga, Vincent] Boston Univ, Dept Dermatol, Boston, MA 02215 USA. [Falanga, Vincent] Boston Univ, Dept Biochem, Boston, MA 02215 USA. [Brem, Harold] NYU, Sch Med, Dept Surg, Div Wound Healing & Regenerat Med, New York, NY USA. [Ennis, William J.] Univ Illinois, Chicago, IL USA. [Wolcott, Randall] SW Reg Wound Care Ctr, Lubbock, TX USA. [Gould, Lisa J.] James A Haley Vet Hosp, Tampa, FL 33612 USA. [Ayello, Elizabeth A.] Excelsior Coll Sch Nursing, Albany, NY USA. RP Falanga, V (reprint author), Roger Williams Med Ctr, Dept Dermatol, NIH Ctr Biomed Res Excellence, 50 Maude St, Providence, RI 02908 USA. EM vfalanga@bu.edu NR 51 TC 22 Z9 23 U1 1 U2 3 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 0889-5899 J9 OSTOMY WOUND MANAG JI Ostomy Wound Manag. PY 2008 SU S BP 2 EP 13 PG 12 WC Surgery SC Surgery GA 323UW UT WOS:000257474900001 ER PT S AU Mohanty, JG Eckley, DM Williamson, JD Launer, LJ Rifkind, JM AF Mohanty, Joy G. Eckley, D. Mark Williamson, J. D. Launer, L. J. Rifkind, Joseph M. BE Kang, KA Harrison, DK Bruley, DF TI Do red blood cell beta-amyloid interactions alter oxygen delivery in Alzheimer's disease? SO OXYGEN TRANSPORT TO TISSUE XXIX SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 34th Annual Conference of the International-Society-on-Oxygen-Transport-to-Tissue CY AUG 12-17, 2006 CL Univ Louisville, Louisville, KY SP Int Soc Oxygen Transport Tissue, Off Univ Provost, Univ Louisville, Off Senior Vice President Res, Univ Louisville, Speed Sch Eng, Univ Louisville, Sch Med & Hlth Sci Ctr, Univ Louisville, Chem Eng Dept, Univ Louisville, Ctr Modeling Integrated Metabolic Syst HO Univ Louisville ID PEPTIDE AB Oxygen delivery requires that Red Blood Cells (RBCs) must be deformable to pass through the microcirculation. Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by abnormal extracellular deposition of beta-amyloid peptide (A beta) and neuronal loss. We have analyzed RBC morphology in blood from subjects with AD and found that > 15% of the RBCs are elongated as compared to 5.9% in normal controls (p<0.0001). To determine whether these morphology changes can be associated with the greater exposure of RBCs to A beta in AD subjects, we investigated the in vitro effect of A beta fibrils on blood. Morphological analysis of RBCs treated with A beta(1-40) or A beta(1-42) fibrils show 8.6% or 11.1 % elongated cells, respectively. In contrast, only 2.9% or 1.3% of RBCs are elongated when blood is treated with buffer or mock fibrils generated from A beta(42-1). Elongated RBCs are expected to be less deformable. This prediction is consistent with our earlier studies showing impaired deformability of RBCs treated with A fibrils. An additional factor previously reported by us, expected to impair the flow of RBCs through the microcirculation is their adherence to endothelial cells (ECs) when A beta(1-40) fibrils are bound to either RBCs or ECs. This factor would be more pronounced in AD subjects with elevated levels of A beta on the vasculature. These results suggest that A beta interactions with RBCs in AD subjects can result in impaired oxygen transport and delivery, which will have important implications for AD. C1 [Mohanty, Joy G.; Rifkind, Joseph M.] NIA, NIH, Mol Dynam Sect, Bethesda, MD 20892 USA. RP Mohanty, JG (reprint author), NIA, NIH, Mol Dynam Sect, Bethesda, MD 20892 USA. EM MOHANTYJ@MAIL.NIH.GOV FU Intramural NIH HHS NR 10 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-74910-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2008 VL 614 BP 29 EP 35 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BHH10 UT WOS:000253182800004 PM 18290311 ER PT J AU Daniels, JL Rowland, AS Longnecker, MP Crawford, P Golding, J AF Daniels, J. L. Rowland, A. S. Longnecker, M. P. Crawford, P. Golding, J. TI Early cognitive development and maternal dental mercury exposure: why not consider ethylmercury exposure? Reply SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Letter C1 [Daniels, J. L.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Daniels, J. L.] Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC 27599 USA. [Longnecker, M. P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Dept Hlth & Human Ser, Res Triangle Pk, NC USA. [Rowland, A. S.] Univ New Mexico, Dept Family & Community Med, MPH Program, Albuquerque, NM 87131 USA. [Crawford, P.] Univ Bristol, Sch Dent, Dept Paediat Dent, Bristol, Avon, England. [Golding, J.] Univ Bristol, Dept Community Based Med, Bristol, Avon, England. RP Daniels, JL (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435, Chapel Hill, NC 27599 USA. EM Julie_daniels@unc.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 2008 VL 22 IS 1 BP 110 EP 111 PG 2 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 263CF UT WOS:000253194500013 ER PT J AU Mitchell, K Yang, HYT Tessier, PA Muhly, WT Swaim, WD Szalayova, I Keller, JM Mezey, E Iadarola, MJ AF Mitchell, Kendall Yang, Hsiu-Ying T. Tessier, Philippe A. Muhly, W. Taylor Swaim, William D. Szalayova, Ildiko Keller, Jason M. Mezey, Eva Iadarola, Michael J. TI Localization of S100A8 and S100A9 expressing neutrophils to spinal cord during peripheral tissue inflammation SO PAIN LA English DT Article DE neutrophils; inflammation; neuroimmunology; innate immune system; nociception; blood-brain barrier ID BLOOD-BRAIN-BARRIER; CALCIUM-BINDING PROTEINS; IN-SITU HYBRIDIZATION; RHEUMATOID-ARTHRITIS; INDUCED HYPERALGESIA; ENDOTHELIAL-CELLS; GLIAL ACTIVATION; FREUNDS-ADJUVANT; ARACHIDONIC-ACID; GENE-EXPRESSION AB Investigation of hyperalgesia at the spinal transcriptome level indicated that carrageenan-induced inflammation of rat hind paws leads to a rapid but sustained increase in S100A8 and S100A9 expression, two genes implicated in the pathology of numerous inflammatory diseases including rheumatoid arthritis and gout. In situ hybridization revealed that the elevation occurred in neutrophils that migrate to the spinal cord vasculature during peripheral inflammation, not in spinal neurons or glial cells. Immunohistochemical analysis suggests, but does not prove, that these neutrophils abundantly release S100A8 and S100A9. Consistent with this, we detected an increase in ICAM and VCAM, both indicators of endothelial activation, a known trigger for secretion of S100A8 and S100A9. Migration of S100A8- and S100A9-expressing neutrophils to spinal cord is selective, since MCP-1- and CD68-expressing leukocytes do not increase in spinal cord vasculature during hind paw inflammation. Examination of many neutrophil granule mediators in spinal cord indicated that they are not regulated to the same degree as S100A8 and S100A9. Neutrophil migration also occurs in the vasculature of brain and pituitary gland during peripheral inflammation. Together, these findings suggest an interaction between a subpopulation of leukocytes and the CNS during peripheral tissue inflammation, as implied by an apparent release and possible diffusion of S100A8 and S100A9 through the endothelial blood-brain barrier. Although the present findings do not establish the neurophysiological or behavioral relevance of these observations to nociceptive processing, the data raise the possibility that selective populations of leukocytes may communicate the presence of disease or tissue damage from the periphery to cells in the central nervous system. (c) 2007 Published by Elsevier B.V. on behalf of International Association for the Study of Pain. C1 [Mitchell, Kendall; Yang, Hsiu-Ying T.; Muhly, W. Taylor; Keller, Jason M.; Iadarola, Michael J.] NIH, Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Tessier, Philippe A.] Univ Laval, Ctr Hosp, Infect Dis Res Ctr, Ste Foy, PQ G1V 4G2, Canada. [Muhly, W. Taylor] NIH, Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD USA. [Swaim, William D.] NIH, Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Gene Transfer Sect,DHHS, Bethesda, MD 20892 USA. [Szalayova, Ildiko; Mezey, Eva] NIH, Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. RP Iadarola, MJ (reprint author), NIH, Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Dept Hlth & Human Serv, 49 Convent Dr, Bethesda, MD 20892 USA. EM miadarola@dir.nidcr.nih.gov RI Tessier, Philippe/A-4466-2010; OI Tessier, Philippe/0000-0001-7177-7763 FU Intramural NIH HHS NR 61 TC 17 Z9 18 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2008 VL 134 IS 1-2 BP 216 EP 231 DI 10.1016/j.pain.2007.10.024 PG 16 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 255YC UT WOS:000252693400025 PM 18063312 ER PT J AU Cookson, MR Greggio, E Lewis, P AF Cookson, Mark R. Greggio, Elisa Lewis, Patrick BE Nass, R Przedborski, S TI THE ROLE OF LRRK2 KINASE ACTIVITY IN CELLULAR PD MODELS SO PARKINSON'S DISEASE: MOLECULAR AND THERAPEUTIC INSIGHTS FROM MODEL SYSTEMS LA English DT Article; Book Chapter ID DISEASE-ASSOCIATED MUTATIONS; FAMILIAL PARKINSONS-DISEASE; GENE LRRK2; NEURONAL TOXICITY; GTP-BINDING; PROTEIN; LRRK2/DARDARIN; DOMAIN; ROC C1 [Cookson, Mark R.; Greggio, Elisa; Lewis, Patrick] NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA. RI Greggio, Elisa/H-6119-2013; OI Greggio, Elisa/0000-0002-8172-3598; Lewis, Patrick/0000-0003-4537-0489 NR 26 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-055958-2 PY 2008 BP 423 EP 431 DI 10.1016/B978-0-12-374028-1.00032-4 PG 9 WC Neurosciences SC Neurosciences & Neurology GA BFF36 UT WOS:000319657700034 ER PT J AU Kittappa, R Chang, W McKay, R AF Kittappa, Raja Chang, Wendy McKay, Ronald BE Nass, R Przedborski, S TI THE ROLE OF THE FOXA2 GENE IN THE BIRTH AND DEATH OF DOPAMINE NEURONS SO PARKINSON'S DISEASE: MOLECULAR AND THERAPEUTIC INSIGHTS FROM MODEL SYSTEMS LA English DT Article; Book Chapter ID CENTRAL-NERVOUS-SYSTEM; EMBRYONIC STEM-CELLS; FLOOR PLATE DIFFERENTIATION; NIGRO-STRIATAL NEURONS; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; TYROSINE-HYDROXYLASE; TRANSCRIPTION FACTOR; SONIC-HEDGEHOG; VENTRAL MIDBRAIN C1 [Kittappa, Raja; Chang, Wendy; McKay, Ronald] Natl Inst Neurol Disorders, Mol Biol Lab, Bethesda, MD 20892 USA. RP Kittappa, R (reprint author), Natl Inst Neurol Disorders, Mol Biol Lab, Bethesda, MD 20892 USA. NR 91 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-055958-2 PY 2008 BP 449 EP 460 DI 10.1016/B978-0-12-374028-1.00034-8 PG 12 WC Neurosciences SC Neurosciences & Neurology GA BFF36 UT WOS:000319657700036 ER PT J AU Goker-Alpan, Z AF Goker-Alpan, Zlem TI Treating patients with Gaucher disease and parkinsonism: Misrepresentation in a title SO PARKINSONISM & RELATED DISORDERS LA English DT Letter ID GLUCOCEREBROSIDASE MUTATIONS C1 NHGRI, Sect Mol Neurogenet Med Genet Branch, Bethesda, MD 20892 USA. RP Goker-Alpan, Z (reprint author), NHGRI, Sect Mol Neurogenet Med Genet Branch, Bldg 35,Room 1A213,35 Convent Dr, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PY 2008 VL 14 IS 1 BP 81 EP 82 DI 10.1016/j.parkreldis.2007.01.002 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 270VG UT WOS:000253747700019 ER PT J AU Houghton, PJ Morton, CL Kolb, EA Lock, R Carol, H Reynolds, CP Keshelava, N Maris, JM Keir, ST Wu, J Smith, MA AF Houghton, Peter J. Morton, Christopher L. Kolb, E. Anders Lock, Richard Carol, Hernan Reynolds, C. Patrick Keshelava, Nino Maris, John M. Keir, Stephen T. Wu, Jianrong Smith, Malcolm A. TI Initial testing (stage 1) of the proteasome inhibitor bortezomib by the pediatric preclinical testing program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE bortezomib; developmental therapeutics; preclinical testing ID FACTOR-KAPPA-B; SQUAMOUS-CELL CARCINOMA; NON-HODGKINS-LYMPHOMA; PHASE-II TRIAL; IN-VIVO; MULTIPLE-MYELOMA; CANCER MODELS; PS-341; APOPTOSIS; INDUCTION AB Background. Bortezomib is a proteasome inhibitor that has been approved by FDA for the treatment of multiple myeloma and that has completed phase 1 testing in children. The purpose of the current study was to evaluate the antitumor activity of bortezomib against the in vitro and in vivo childhood cancer preclinical models of the Pediatric Preclinical Testing Program (PPTP). Procedures. Bortezomib was tested against the PPTP in vitro panel at concentrations ranging from 0.1 nM to 1.0 mu M and was tested in vivo at a dose of 1 mg/kg for a planned duration of 6 weeks. Results. Bortezomib was uniformly active against the PPTP's in vitro panel, with a median IC50 of 23 nM and with a steep dose-response curve. The four acute lymphoblastic leukemia (ALL) cell lines had significantly lower IC50 values compared to the remaining lines of the in vitro panel. Limited in vivo activity was observed for bortezomib against the solid tumor xenografts tested, with one line meeting criteria for intermediate activity for the time to event measure and with the remaining lines showing low activity for this measure. Bortezomib demonstrated in vivo activity against the ALL panel, inducing two complete and two partial responses among seven evaluable lines. Conclusions. Administered at its MTD in mice, bortezomib demonstrated activity against selected lines of the PPTP's ALL in vivo panel. Further studies are indicated to determine the activity of bortezomib when combined with standard agents to treat childhood ALL. C1 St Jude Childrens Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. Childrens Hosp Montefiore, Bronx, NY USA. Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. Abramson Family Canc Res Inst, Philadelphia, PA USA. Duke Univ, Med Ctr, Durham, NC USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Houghton, PJ (reprint author), St Jude Childrens Hosp, Dept Mol Pharmacol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM peter.houghton@stjude.org RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013; OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C. Patrick/0000-0002-2827-8536 FU NCI NIH HHS [N01-CM-42216] NR 50 TC 79 Z9 80 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2008 VL 50 IS 1 BP 37 EP 45 DI 10.1002/pbc.21214 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 237XT UT WOS:000251410400007 PM 17420992 ER PT J AU Meert, KL Eggly, S Pollack, M Anand, KJS Zimmerman, J Carcillo, J Newth, CJL Dean, JM Willson, DF Nicholson, C AF Meert, Kathleen L. Eggly, Susan Pollack, Murray Anand, K. J. S. Zimmerman, Jerry Carcillo, Joseph Newth, Christopher J. L. Dean, J. Michael Willson, Douglas F. Nicholson, Carol CA Natl Inst Child Hlth TI Parents' perspectives on physician-parent communication near the time of a child's death in the pediatric intensive care unit SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE communication; critical care; physicians; parents; prognosis; death ID OF-LIFE CARE; PALLIATIVE CARE; BAD-NEWS; FAMILY PERSPECTIVES; CANCER-PATIENTS; END; PROGNOSIS; QUALITY; EDUCATION AB Objective: Communicating bad news about a child's illness is a difficult task commonly faced by intensive care physicians. Greater understanding of parents' scope of experiences with bad news during their child's hospitalization will help physicians communicate more effectively. Our objective is to describe parents' perceptions of their conversations with physicians regarding their child's terminal illness and death in the pediatric intensive care unit (PICU). Design: A secondary analysis of a qualitative interview study. Setting: Six children's hospitals in the National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Participants: Fifty-six parents of 48 children who died in the PICU 3-12 months before the study. Interventions. Parents participated in audio recorded semi-structured telephone interviews. Interviews were analyzed using established qualitative methods. Measurements and Main Results: Of the 56 parents interviewed, 40 (71%) wanted to provide feedback on the way information about their child's terminal illness and death was communicated by PICU physicians. The most common communication issue identified by parents was the physicians' availability and attentiveness to their informational needs. Other communication issues included honesty and comprehensiveness of information, affect with which information was provided, withholding of information, provision of false hope, complexity of vocabulary, pace of providing information, contradictory information, and physicians' body language. Conclusions: The way bad news is discussed by physicians is extremely important to most parents. Parents want physicians to be accessible and to provide honest and complete information with a caring affect, using lay language, and at a pace in accordance with their ability to comprehend. Withholding prognostic information from parents often leads to false hopes and feelings of anger, betrayal, and distrust. Future research is needed to investigate whether the way bad news is discussed influences psychological adjustment and family functioning among bereaved parents. C1 [Meert, Kathleen L.] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Eggly, Susan] Karmanos Canc Inst, Detroit, MI USA. [Pollack, Murray] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Anand, K. J. S.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Zimmerman, Jerry] Seattle Childrens Hosp, Seattle, WA USA. [Carcillo, Joseph] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Newth, Christopher J. L.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Dean, J. Michael] Univ Utah, Salt Lake City, UT 84112 USA. [Willson, Douglas F.] Univ Virginia, Childrens Hosp, Charlottesville, VA 22903 USA. [Nicholson, Carol] NICHHD, Bethesda, MD 20892 USA. RP Meert, KL (reprint author), Childrens Hosp Michigan, 3901 Beaubien Blvd, Detroit, MI 48201 USA. EM kmeert@med.wayne.edu OI Anand, Kanwaljeet/0000-0001-6498-1483; Eggly, Susan/0000-0002-8137-6098 FU NICHD NIH HHS [U10 HD049945, U01 HD049934, U01HD049934, U10 HD049981, U10 HD049983, U10 HD050012, U10 HD050096, U10HD049945, U10HD049981, U10HD049983, U10HD050012, U10HD050096, U10HD500009, UG1 HD050096] NR 28 TC 83 Z9 83 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD JAN PY 2008 VL 9 IS 1 BP 2 EP 7 DI 10.1097/01.PCC.0000298644.13882.88 PG 6 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 252QR UT WOS:000252462200002 PM 18477906 ER PT J AU Honda, M Nagamine, T Yamashiro, K Shimoji, T AF Honda, Masaru Nagamine, Tomoaki Yamashiro, Katsumi Shimoji, Takeyoshi TI An intracranial pseudoaneurysm in the distal middle cerebral artery in a child SO PEDIATRIC NEUROSURGERY LA English DT Article DE intracranial aneurysm; pseudoaneurysm ID ANEURYSMS; ADOLESCENCE; TRAUMA AB Intracranial pseudoaneurysms are rare, particularly in children and adolescents. They are characterized by the presence of organizing hematoma and fibrosis without true vascular elements. Most pseudoaneurysms result from events such as major trauma or infectious illness, and the development of pseudoaneurysm without a preceding incident is rare. We here describe a patient with a large pseudoaneurysm arising in the distal middle cerebral artery. A 10-year-old boy experienced a sudden onset of headache, nausea, and vomiting followed by loss of consciousness and was referred to our medical center. Brain computed tomography showed massive subcortical hemorrhage in the left temporal lobe. Digital cerebral angiography revealed a huge aneurysmal dilatation of the distal left M1 segment of the middle cerebral artery, with delayed filling and emptying of contrast media. Surgical resection of the aneurysm with evacuation of the hematoma yielded restoration of consciousness. Although the cause of aneurysm in this case is uncertain, this type of patient is seldom encountered; its etiology and mechanisms of onset are discussed with reference to the literature. Copyright (C) 2008 S. Karger AG, Basel. C1 Okinawa Nanbu Med Ctr, Dept Neurosurg, Haebaru, Japan. Childrens Med Ctr, Haebaru, Japan. RP Honda, M (reprint author), NIMH, Pharmacol Sect, NIH, Bldg 10,Rm 2D57,10 Ctr Dr,MSC 1514,9000 Rockville, Bethesda, MD 20892 USA. EM hmasaru@mail.nih.gov NR 17 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-2291 J9 PEDIATR NEUROSURG JI Pediatr. Neurosurg. PY 2008 VL 44 IS 5 BP 426 EP 429 DI 10.1159/000149914 PG 4 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 356NX UT WOS:000259786000015 PM 18703893 ER PT J AU Hunt, CE Corwin, MJ Lister, G Weese-Mayer, DE Ward, SLD Tinsley, LR Neuman, MR Willinger, M Ramanathan, R Rybin, D AF Hunt, Carl E. Corwin, Michael J. Lister, George Weese-Mayer, Debra E. Ward, Sally L. Davidson Tinsley, Larry R. Neuman, Michael R. Willinger, Marian Ramanathan, Rangasamy Rybin, Denis CA Study Grp TI Precursors of cardiorespiratory events in infants detected by home memory monitor SO PEDIATRIC PULMONOLOGY LA English DT Article DE apnea; bradycardia; sudden infant death syndrome (SIDS); hemoglobin O-2; saturation (SpO(2)); prematurity ID DEATH-SYNDROME; HEALTHY INFANTS; APNEA; RISK AB In 1,079 infants monitored for > 700,000 hr at home for apnea or bradycardia, we found an association between infants having multiple events exceeding conventional or a priori defined more extreme thresholds and less favorable developmental outcome at 1 year of age than infants with few or no events. If it is necessary to prevent such events to minimize risk for developmental morbidity, there is reason to determine whether there are disturbances in advance of the apnea or bradycardia that herald their onset. In the 85 infants with at least 1 extreme event and 1 conventional event, we hypothesized that apnea and bradycardia do not occur de novo but rather are preceded by cardiorespiratory and hemoglobin O-2 saturation changes. We compared recorded time intervals preceding these events, and we analyzed three preceding time intervals for each conventional and extreme event, and each non-event recording: Time-2 hr: up to 2 hr before; Time-1 hr: up to 1 hr before; and Time-75 sec: the 75 sec immediately preceding each event. O-2 saturation progressively decreased preceding both conventional and extreme events, and progressive increases occurred in heart and breathing rate variability Duration of respiratory pauses and of periodic breathing progressively increased preceding conventional events, respiratory rate variability increased immediately preceding conventional events and at 1 hr preceding extreme events, and O-2 saturation decreased immediately preceding both conventional and extreme events. Thus, conventional and extreme events do not occur de novo but rather are preceded by autonomic instability of the cardiorespiratory system. C1 [Hunt, Carl E.] Univ Toledo, Ctr Hlth Sci, Dept Pediat, Toledo, OH 43606 USA. [Corwin, Michael J.; Rybin, Denis] Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Corwin, Michael J.; Rybin, Denis] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Corwin, Michael J.; Rybin, Denis] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Lister, George] UTSW Med Sch, Dept Pediat, Dallas, TX USA. [Weese-Mayer, Debra E.] Rush Univ, Rush Med Coll, Dept Pediat, Chicago, IL 60612 USA. [Ward, Sally L. Davidson; Ramanathan, Rangasamy] USC, Childrens Hosp Los Angeles, Keck Sch Med, Dept Pediat, Los Angeles, CA USA. [Tinsley, Larry R.] Univ Hawaii, John A Burns Sch Med, Dept Pediat, Honolulu, HI 96822 USA. [Neuman, Michael R.] Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH USA. [Willinger, Marian] NICHHD, NIH, Bethesda, MD 20892 USA. [Corwin, Michael J.; Rybin, Denis] Boston Univ, Sch Publ Hlth, Dept Pediat, Boston, MA 02215 USA. [Corwin, Michael J.; Rybin, Denis] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Corwin, Michael J.; Rybin, Denis] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Hunt, CE (reprint author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20892 USA. EM huntc@mail.nih.gov OI Rybin, Denis/0000-0002-3657-4829; Corwin, Michael/0000-0002-6591-209X FU NICHD NIH HHS [HD 29067, HD 20056, HD 28971, HD 29060, HD 29071, HD 29073, HD 34625] NR 16 TC 15 Z9 16 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD JAN PY 2008 VL 43 IS 1 BP 87 EP 98 DI 10.1002/ppul.20745 PG 12 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 254LL UT WOS:000252588000012 PM 18041078 ER PT J AU Aune, CN Chatterjee, B Zhao, XQ Francis, R Bracero, L Yu, Q Rosenthal, J Leatherbury, L Lo, CW AF Aune, Christine N. Chatterjee, Bishwanath Zhao, Xiao-Qing Francis, Richard Bracero, Luciann Yu, Qing Rosenthal, Julie Leatherbury, Linda Lo, Cecilia W. TI Mouse model of heterotaxy with single ventricle spectrum of cardiac anomalies SO PEDIATRIC RESEARCH LA English DT Article ID PRIMARY CILIARY DYSKINESIA; LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS; CONGENITAL HEART-DISEASE; SITUS-INVERSUS; NODAL FLOW; DEFECTS; MUTATIONS; MICE; NUMB AB Heterotaxy arises from a failure of the embryo to establish normal left-right asymmetry and is known to affect 3% of infants with congenital heart disease. A recessive mutation causing heterotaxy was recovered in a mouse mutagenesis screen focused on congenital heart defects. Homozygote mutants exhibit abnormal situs in the thoracic and abdominal cavities. Dextrocardia, levocardia, or mesocardia was seen together with right pulmonary isomerism and complex structural heart defects in the single ventricle spectrum. A dominant chamber of left ventricular morphology positioned on the left or right is seen together with transposition of the great arteries. Right atrial isomerism with or without total anomalous pulmonary venous connection was observed in half of the mutants. Because ciliary motion at the embryonic node is required for the specification of laterality, we examined the tracheal epithelia of newborn mice as a proxy for the nodal cilia. However, videomicroscopy showed no defect in ciliary motion. Genome scanning using polymorphic microsatellite markers mapped the mutation to a 3.3 Mb interval on mouse chromosome 7. None of the genes previously described for familial heterotaxy were found in this interval, indicating a novel mutation in this mouse model of heterotaxy. C1 [Aune, Christine N.; Chatterjee, Bishwanath; Zhao, Xiao-Qing; Francis, Richard; Bracero, Luciann; Yu, Qing; Rosenthal, Julie; Leatherbury, Linda; Lo, Cecilia W.] NHLBI, NIH, Dev Biol Lab, Bethesda, MD 20892 USA. [Aune, Christine N.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. [Aune, Christine N.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Lo, CW (reprint author), NHLBI, NIH, 10 Ctr Dr MSC 1583, Bethesda, MD 20809 USA. EM loc@nhlbi.nih.gov RI Francis, Richard/P-2524-2015 FU NHLBI NIH HHS [ZO1-HL005701] NR 40 TC 10 Z9 10 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2008 VL 63 IS 1 BP 9 EP 14 PG 6 WC Pediatrics SC Pediatrics GA 244SK UT WOS:000251885400003 PM 18043505 ER PT J AU Jansson, LM Choo, R Velez, ML Harrow, C Schroeder, JR Shakleya, DM Huestis, MA AF Jansson, Lauren M. Choo, Robin Velez, Martha L. Harrow, Cheryl Schroeder, Jennifer R. Shakleya, Diaa M. Huestis, Marilyn A. TI Methadone maintenance and breastfeeding in the neonatal period SO PEDIATRICS LA English DT Article DE lactation; breast milk; methadone ID 2-ETHYLIDENE-1,5-DIMETHYL-3,3-DIPHENYLPYRROLIDINE EDDP; PERINATAL-PERIOD; PREGNANT-WOMEN; MANAGEMENT; MILK; PLASMA; QUANTIFICATION; WITHDRAWAL; ADDICTION; LACTATION AB OBJECTIVE. In a sample of methadone-maintained breastfeeding women and a matched group of formula-feeding women, this study evaluated concentrations of methadone in breast milk among breastfeeding women and concentrations of methadone in maternal and infant plasma in both groups. METHODS. Eight methadone-maintained (dose: 50-105 mg/day), lactating women provided blood and breast milk specimens on days 1, 2, 3, 4, 14, and 30 after delivery, at the times of trough and peak maternal methadone levels. Paired specimens of foremilk and hindmilk were obtained at each sampling time. Eight matched formula-feeding subjects provided blood samples on the same days. Infant blood samples for both groups were obtained on day 14. Urine toxicological screening between 36 weeks of gestation and 30 days after the birth confirmed that subjects were not using illicit substances in the perinatal period. RESULTS. Concentrations of methadone in breast milk were low (range: 21.0-462.0 ng/mL) and not related to maternal dose. There was a significant increase in methadone concentrations in breast milk over time for all 4 sampling times. Concentrations of methadone in maternal plasma were not different between groups and were unrelated to maternal dose. Concentrations of methadone in infant plasma were low (range: 2.2-8.1 ng/mL) in all samples. Infants in both groups underwent neurobehavioral assessments on days 3, 14, and 30; there were no significant effects of breastfeeding on neurobehavioral outcomes. Fewer infants in the breastfed group required pharmacotherapy for neonatal abstinence syndrome, but this was not a statistically significant finding. CONCLUSION. Results contribute to the recommendation of breastfeeding for methadone-maintained women. C1 [Jansson, Lauren M.; Velez, Martha L.] Johns Hopkins Univ, Sch Med, Ctr Addict & Pregnancy, Dept Pediat, Baltimore, MD 21224 USA. [Choo, Robin; Shakleya, Diaa M.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Chem & Drug Metab Sect, Intramural Res Program, Baltimore, MD USA. [Schroeder, Jennifer R.] Natl Inst Drug Abuse, Off Clin Director, Intramural Res Program, Baltimore, MD USA. [Choo, Robin] Univ Pittsburgh, Div Nat Sci, Titusville, PA USA. [Harrow, Cheryl] Johns Hopkins Bayview Med Ctr, Div Neonatol, Baltimore, MD USA. RP Jansson, LM (reprint author), Johns Hopkins Univ, Sch Med, Ctr Addict & Pregnancy, Dept Pediat, 4940 Eastern Ave,D5, Baltimore, MD 21224 USA. EM ljansson@jhmi.edu FU Intramural NIH HHS; NIDA NIH HHS [R01 DA019934, K08 DA00495] NR 45 TC 58 Z9 60 U1 1 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2008 VL 121 IS 1 BP 106 EP 114 DI 10.1542/peds.2007-1182 PG 9 WC Pediatrics SC Pediatrics GA 247RC UT WOS:000252096300014 PM 18166563 ER PT J AU Vergura, R Balboni, G Spagnolo, B Gavioli, E Lambert, DG McDonald, J Trapella, C Lazarus, LH Regoli, D Guerrini, R Salvadori, S Calo, G AF Vergura, Raffaella Balboni, Gianfranco Spagnolo, Barbara Gavioli, Elaine Lambert, David G. McDonald, John Trapella, Claudio Lazarus, Lawrence H. Regoli, Domenico Guerrini, Remo Salvadori, Severo Calo, Girolamo TI Anxiolytic- and antidepressant-like activities of H-Dmt-Tic-NH-CH(CH2-COOH)-Bid (UFP-512), a novel selective delta opioid receptor agonist SO PEPTIDES LA English DT Article DE UFP-512; DOP receptor; receptor binding; bioassay; forced swimming test; light-dark aversion; elevated plus-maze test ID FORCED-SWIMMING TEST; LEARNED HELPLESSNESS MODEL; MESSENGER-RNA EXPRESSION; DMT-TIC PHARMACOPHORE; IN-VIVO; ENDOGENOUS ENKEPHALINS; EMOTIONAL RESPONSES; MICE DEFICIENT; RAT-BRAIN; FQ AB Knockout and pharmacological studies have shown that delta opioid peptide (DOP) receptor signalling regulates emotional responses. In the present study, the in vitro and in vivo pharmacological profile of the DOP ligand, H-Dmt-Tic-NH-CH(CH2-COOH)-Bid (UFP-512) was investigated. In receptor binding experiments performed on membranes of CHO cells expressing the human recombinant opioid receptors, UFP-512 displayed very high affinity (pK(i) 10.20) and selectivity (>150-fold) for DOP sites. In functional studies ([S-35]GTP gamma S binding in CHOhDOP membranes and electrically stimulated mouse vas deferens) UFP-512 behaved as a DOP selective full agonist showing potency values more than 100-fold higher than DPDPE. In vivo, in the mouse forced swimming test, UFP-512 reduced immobility time both after intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration. Similar effects were recorded in rats. Moreover, UFP-512 evoked anxiolytic-like effects in the mouse elevated plus maze and light-dark aversion assays. All these in vivo actions of UFP-512 were fully prevented by the selective DOP antagonist naltrindole (3 mg/kg, s.c.). In conclusion, the present findings demonstrate that UFP-512 behaves as a highly potent and selective agonist at DOP receptors and corroborate the proposal that the selective activation of DOP receptors elicits robust anxiolytic- and antidepressant-like effects in rodents. (C) 2007 Elsevier Inc. All rights reserved. C1 [Vergura, Raffaella; Spagnolo, Barbara; Gavioli, Elaine; Regoli, Domenico; Calo, Girolamo] Univ Ferrara, Dept Expt & Clin Med, Pharmacol Sect, I-44100 Ferrara, Italy. [Vergura, Raffaella; Spagnolo, Barbara; Gavioli, Elaine; Regoli, Domenico; Calo, Girolamo] Univ Ferrara, Natl Inst Neurosci, I-44100 Ferrara, Italy. [Balboni, Gianfranco; Guerrini, Remo; Salvadori, Severo] Univ Ferrara, Dept Pharmaceut Sci & Biotechnol Ctr, I-44100 Ferrara, Italy. [Balboni, Gianfranco] Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. [Lambert, David G.; McDonald, John] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England. [Trapella, Claudio] UFPeptides srl, Ferrara, Italy. [Lazarus, Lawrence H.] Natl Inst Environm Hlth Sci, Chem Pharmacol Lab, Med Chem Grp, Res Triangle Pk, NC USA. RP Calo, G (reprint author), Univ Ferrara, Dept Expt & Clin Med, Pharmacol Sect, Via Fossato Mortara 19, I-44100 Ferrara, Italy. EM g.calo@unife.it RI Gavioli, Elaine/G-5075-2012; Lambert, David/B-2629-2012; Trapella, Claudio/I-2128-2012; OI Gavioli, Elaine/0000-0001-8967-1369; Trapella, Claudio/0000-0002-6666-143X; Guerrini, Remo/0000-0002-7619-0918; SALVADORI, Severo/0000-0002-8224-2358 FU Intramural NIH HHS [NIH0010172798, Z01 ES090053-20, Z01 ES100472-06] NR 43 TC 39 Z9 41 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JAN PY 2008 VL 29 IS 1 BP 93 EP 103 DI 10.1016/j.peptides.2007.10.012 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 254LR UT WOS:000252588600013 PM 18069089 ER PT J AU Kohler, A Weigelt, S Muckli, L Singer, W Kriegeskorte, N AF Kohler, A. Weigelt, S. Muckli, L. Singer, W. Kriegeskorte, N. TI Patterns of fMRI activity representing perceived direction in apparent motion SO PERCEPTION LA English DT Meeting Abstract C1 [Kohler, A.; Weigelt, S.; Singer, W.] Max Planck Inst Brain Res, Dept Neurophysiol, D-60528 Frankfurt, Germany. [Muckli, L.] Univ Glasgow, Dept Psychol, Glasgow G12 8QQ, Lanark, Scotland. [Muckli, L.] Univ Glasgow, CCNI, Glasgow G12 8QQ, Lanark, Scotland. [Kriegeskorte, N.] NIMH, Lab Brain & Cognit, Sect Funct Imaging Methods, Bethesda, MD 20892 USA. EM akohler@mpih-franfurt.mpg.de RI Muckli, Lars/B-3119-2009; Singer, Wolf/D-6874-2012 OI Muckli, Lars/0000-0002-0143-4324; NR 0 TC 0 Z9 0 U1 0 U2 2 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2008 VL 37 SU S BP 25 EP 25 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 406BL UT WOS:000263269900088 ER PT J AU Sommer, MA Wurtz, RH AF Sommer, Marc A. Wurtz, Robert H. TI Visual perception and corollary discharge SO PERCEPTION LA English DT Article; Proceedings Paper CT Interdisciplinary Conference on Pre-Emptive Perception CY OCT 15-18, 2005 CL Hanse Inst Adv Studies, Delmenhorst, GERMANY HO Hanse Inst Adv Studies ID FRONTAL EYE FIELD; BRAIN-STEM TELLS; SUPERIOR COLLICULUS; RHESUS-MONKEY; CORTEX; PARIETAL; THALAMUS; MOVEMENTS; NUCLEUS; NEURONS AB Perception depends not only on sensory input but also on the state of the brain receiving that input. A classic example is perception of a stable visual world in spite of the saccadic eye movements that shift the images on the retina. A long-standing hypothesis is that the brain compensates for the disruption of visual input by using advance knowledge of the impending saccade, an internally generated corollary discharge. One possible neuronal mechanism for this compensation has been previously identified in parietal and frontal cortex of monkeys, but the origin of the necessary corollary discharge remained unknown. Here, we consider recent experiments that identified a pathway for a corollary discharge for saccades that extends from the superior colliculus in the midbrain to the frontal eye fields in the cerebral cortex with a relay in the medial dorsal nucleus of the thalamus. We first review the nature of the evidence used to identify a corollary discharge signal in the complexity of the primate brain and show its use for guiding a rapid sequence of eye movements. We then consider two experiments that show this same corollary signal may provide the input to the frontal cortex neurons that alters their activity with saccades in ways that could compensate for the displacements in the visual input produced by saccadic eye movements. The first experiment shows that the corollary discharge signal is spatially and temporally appropriate to produce the alterations in the frontal-cortex neurons. The second shows that this signal is necessary for this alteration because inactivation of the corollary reduces the compensation by frontal-cortex neurons. The identification of this relatively simple circuit specifies the organization of a corollary discharge in the primate brain for the first time and provides a specific example upon which consideration of the roles of corollary activity in other systems and for other functions can be evaluated. C1 [Sommer, Marc A.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA. [Sommer, Marc A.] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15260 USA. [Sommer, Marc A.; Wurtz, Robert H.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Sommer, MA (reprint author), Univ Pittsburgh, Dept Neurosci, A210 Langley Hall, Pittsburgh, PA 15260 USA. EM masommer@pitt.edu FU Intramural NIH HHS [Z01 EY000109-27]; NEI NIH HHS [R01 EY017592] NR 20 TC 26 Z9 26 U1 1 U2 7 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2008 VL 37 IS 3 BP 408 EP 418 DI 10.1068/p5873 PG 11 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 300TF UT WOS:000255847400009 PM 18491718 ER PT S AU Scholtz, J Theofanos, M Consolvo, S AF Scholtz, Jean Theofanos, Mary Consolvo, Sunny BE Kourouthanassis, PE Giaglis, GM TI A FRAMEWORK FOR THE EVALUATION OF PERVASIVE INFORMATION SYSTEMS SO PERVASIVE INFORMATION SYSTEMS SE Advances in Management Information Systems LA English DT Article; Book Chapter DE Evaluation; Measures; Methodologies; Metrics; Pervasive Computing ID COMPUTER; TECHNOLOGY; ACCEPTANCE; DESIGN; ISSUES; MODELS AB As pervasive information systems weave their way into society, it is critical that these new systems are accepted and utilized. However, it is difficult to determine what makes for a good design and a successful interaction because evaluation methodologies and metrics are in their infancy for these types of systems. The complexity and diversity of these systems has made it difficult to establish common evaluation techniques and practices. However, the necessity for such a framework is overwhelmingly apparent. A framework will make it easier for researchers to learn from each other's results, create effective discount evaluation techniques and design guidelines for pervasive computing, provide a mechanism for researchers to share what they have learned about the appropriateness of different evaluation techniques, and provide structure so that key areas of evaluation are not overlooked. In this chapter, we present a framework of areas of evaluation for pervasive information systems. The framework includes nine evaluation areas that include elements of usability, interaction, and values (such as privacy and trust). We present sample metrics and measures and examples for each area from the literature. We review a number of methodologies that have been used in evaluation and provide a case study of an evaluation using a number of the evaluation areas in the framework. We conclude with a discussion of future needs to enable researchers to share evaluation results. C1 [Scholtz, Jean; Theofanos, Mary] NIST, Visualizat & Usabil Grp, Ind Usabil Reporting Project, Gaithersburg, MD 20899 USA. [Scholtz, Jean] Berkeleys Endeavor Project, Berkeley, CA USA. [Scholtz, Jean] Intel Corp, Santa Clara, CA 95051 USA. [Scholtz, Jean] Portland State Univ, Fac Comp Sci, Portland, OR 97207 USA. [Theofanos, Mary] Natl Canc Inst, Commun Technol Res Ctr, Bethesda, MD 20892 USA. [Theofanos, Mary] US DOE, Washington, DC 20585 USA. RP Scholtz, J (reprint author), NIST, Visualizat & Usabil Grp, Ind Usabil Reporting Project, Gaithersburg, MD 20899 USA. NR 49 TC 0 Z9 0 U1 0 U2 1 PU M E SHARPE INC PI ARMONK PA 80 BUSINESS PARK DRIVE, ARMONK, NY 10504 USA SN 1554-6152 BN 978-0-7656-1689-0 J9 ADV MANAG INFORM SYS PY 2008 VL 10 BP 210 EP 231 PG 22 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA BRQ88 UT WOS:000283438800012 ER PT J AU Zhang, L Ding, H Yan, J Hui, R Wang, W Kissling, GE Zeldin, DC Wang, DW AF Zhang, Laxi Ding, Hu Yan, Jiangtao Hui, Rutai Wang, Wei Kissling, Grace E. Zeldin, Darryl C. Wang, Dao Wen TI Genetic variation in cytochrorne P450 2J2 and soluble epoxide hydrolase and risk of ischemic stroke in a Chinese population SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE CYP2J2; cytochrorne P450; EPHX2; genetics; ischemic stroke; polymorphism ID NITRIC-OXIDE SYNTHASE; EPOXYGENASE-DERIVED EICOSANOIDS; ACTIVATED PROTEIN-KINASE; ARACHIDONIC-ACID; EPOXYEICOSATRIENOIC ACIDS; SIGNALING PATHWAYS; BLOOD-PRESSURE; CYTOCHROME-P450; DISEASE; ATHEROSCLEROSIS AB Objective Epoxyeicosatrienoic acids have been recognized for their protective effects on the cardiovascular system. This study investigated whether two common polymorphisms in genes believed to be influential in regulating circulating levels of epoxyeicosatrienoic acids, namely cytochrome P450 2J2 (CYP2J2) G-50T and soluble epoxide hydrolase (EPHX2) G860A, were associated with ischemic stroke risk in a Chinese population. Methods and results Screening of 200 patients with ischernic stroke and 350 control participants revealed that CYP2J2-50T allele frequency was not significantly different in ischernic stroke cases versus controls. In contrast, EPHX2 860A allele frequency was 16.8% in ischemic stroke cases versus 21.7% in controls (P=0.047), and the presence of this variant allele was associated with a significantly lower risk of ischernic stroke after adjustment for sex, age and multiple cardiovascular risk factors (adjusted odds ratio=0.50, 95% confidence interval 0.29-0.86). Moreover, there was a significant interaction between the EPHX2 G860A polymorphism, smoking and ischernic stroke risk such that nonsmokers carrying the EPHX2 G860A variant allele were at the lowest risk of ischernic stroke (odds ratio= 0.33, 95% confidence interval, Conclusions Collectively, these data indicate a protective influence of the G860A polymorphism of EPHX2 on ischemic stroke in Chinese nonsmokers. Pharmacogenetics and Genomics 18:45-51 (c) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Zhang, Laxi; Ding, Hu; Yan, Jiangtao; Wang, Wei; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Inst Hypertens, Wuhan 430030, Peoples R China. [Hui, Rutai] Chinese Acad Med Sci, Beijing 100037, Peoples R China. [Hui, Rutai] Fuwai Hosp, Peking Union Med Coll, Beijing 100037, Peoples R China. [Kissling, Grace E.; Zeldin, Darryl C.] Natl Inst Hlth, Natl Inst Environm Hlth Sci, Div Intramural Res, Res Triangle Pk, NC USA. RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Inst Hypertens, 1095 Jiefang Ave, Wuhan 430030, Peoples R China. EM dwwang@tjh.tjmu.edu.cn FU Intramural NIH HHS [Z01 ES025034-13] NR 42 TC 38 Z9 41 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD JAN PY 2008 VL 18 IS 1 BP 45 EP 51 DI 10.1097/FPC.0b013e3282f313e8 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 246KM UT WOS:000252005900005 PM 18216721 ER PT J AU Reissig, CJ Eckler, JR Rabin, RA Rice, KC Winter, JC AF Reissig, C. J. Eckler, J. R. Rabin, R. A. Rice, K. C. Winter, J. C. TI The stimulus effects of 8-OH-DPAT: Evidence for a 5-HT2A receptor-mediated component SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE 8-OH-DPAT; 5-HT2A receptor; Stimulus control; M100907; 5-HT1A ID PREFRONTAL CORTEX; FUNCTIONAL INTERACTION; 5-HYDROXYTRYPTAMINE1A RECEPTORS; SEROTONIN(2A) RECEPTOR; DISCRIMINATIVE STIMULI; HALLUCINOGENIC DRUGS; HUMAN BRAIN; ANTAGONIST; RAT; SCHIZOPHRENIA AB A previous investigation in our laboratory found that the stimulus effects of the 5-HT2A agonist, LSD, are potentiated by 5-HT1A receptor agonists including the prototypic agonist, 8-OH-DPAT Also suggestive of behaviorally relevant interactions between 5-HT1A and 5-HT2A receptors are behavioral analyses of locomotor activity, head-twitch response, forepaw treading and production of the serotonin syndrome; in some instances effects are augmented, in other, diminished. These observations led us in the present investigation to test the hypothesis that stimulus control by 8-OH-DPAT [0.2 mg/kg; 15 min pretreatment time] is modulated by 5-HT2A ligands. Stimulus control was established with 8-OH-DPAT in a group of 10 rats. A two-lever, fixed ratio 10, positively reinforced task with saline controls was employed. As shown previously, stimulus control by 8-OH-DPAT and the generalization of 8-OH-DPAT to the 5-HT1A partial agonist, buspirone, was completely blocked by the selective 5-HT1A antagonist, WAY-100635. In contrast, antagonism by the selective 5-HT2A antagonist, M100907 [0.1 mg/kg; 30 min pretreatment time], of 8-OH-DPAT and of the generalization of 8-OH-DPAT to buspirone was statistically significant but less than complete. In light of our previous conclusions regarding the interactions of 5-HT1A agonists with LSD-induced stimulus control, the present data suggest that the interaction between 5-HT1A and 5-HT2A receptors is bidirectional in drug discrimination studies. (C) 2007 Elsevier Inc. All rights reserved. C1 [Reissig, C. J.; Eckler, J. R.; Rabin, R. A.; Winter, J. C.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA. [Rice, K. C.] NIH, NIDDK, Med Chem Lab, Bethesda, MD 20892 USA. RP Winter, JC (reprint author), SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, 102 Farber Hall, Buffalo, NY 14214 USA. EM jcwinter@buffalo.edu FU NIDA NIH HHS [R01 DA003385-18] NR 54 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 2008 VL 88 IS 3 BP 312 EP 317 DI 10.1016/j.pbb.2007.09.011 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 260RB UT WOS:000253026700016 PM 17936346 ER PT J AU Fantegrossi, WE Reissig, CJ Katz, EB Yarosh, HL Rice, KC Winter, JC AF Fantegrossi, William E. Reissig, Chad J. Katz, Elyse B. Yarosh, Haley L. Rice, Kenner C. Winter, Jerrold C. TI Hallucinogen-like effects of N,N-dipropyltryptamine (DPT): Possible mediation by serotonin 5-HT1A and 5-HT2A receptors in rodents SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE hallucinogens; drug discrimination; head-twitch response; serotonin receptors ID INDUCED STIMULUS-CONTROL; HEAD-TWITCH RESPONSE; LSD; DRUGS; RATS; MICE; 5-HYDROXYTRYPTAMINE; ANTAGONIST; BEHAVIOR; BRAIN AB N,N-dipropyltryptamine (DPT) is a synthetic tryptamine hallucinogen which has been used psychotherapeutically in humans, but has been studied preclinically only rarely. In the present studies, DPT was tested in a drug-elicited head-twitch assay in mice, and in rats trained to discriminate lysergic acid diethylamide (LSD), N,N-dimethyl-4-phosphoryloxytryptamine (psilocybin), or 3,4-methylenedioxymethamphetamine (MDMA). A separate group of rats was also trained to recognize DPT itself as a discriminative stimulus, and in all cases, the behavioral effects of DPT were challenged with the selective serotonin (5-HT)(2A) antagonist M100907, the 5-HT1A selective antagonist WAY-100635, or their combination. In the head-twitch assay, DPT elicited dose-dependent effects, producing a biphasic dose-effect curve. WAY-100635 produced a parallel rightward shift in the dose-effect curve for head twitches, indicative of surmountable antagonism, but the antagonist effects of M100907 were functionally insurmountable. DPT produced partial to full substitution when tested in rats trained to discriminate LSD, psilocybin or MDMA, and served as a discriminative stimulus. In all cases, the antagonist effects of M100907 were more profound than were those of WAY-100635. DPT is thus active in two rodent models relevant to 5-HT2 agonist activity. The effectiveness with which M100907 antagonizes the behavioral actions of this compound strongly suggest that the 5-HT2A receptor is an important site of action for DPT, but the modulatory actions of WAY-100635 also imply a 5-HT1A-mediated component to the actions of this compound. (C) 2007 Elsevier Inc. All rights reserved. C1 [Fantegrossi, William E.; Katz, Elyse B.; Yarosh, Haley L.] Yerkes Natl Primate Res Ctr, Div Neurosci, Atlanta, GA 30322 USA. [Reissig, Chad J.; Winter, Jerrold C.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, Buffalo, NY 14260 USA. [Rice, Kenner C.] NIH, Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD 20892 USA. RP Fantegrossi, WE (reprint author), Yerkes Natl Primate Res Ctr, Div Neurosci, 954 Gatewood Rd, Atlanta, GA 30322 USA. EM wfanteg@emory.edu FU NIDA NIH HHS [R01 DA003385, DA03385, R21 DA020645, R21 DA020645-02, DA016457, R56 DA003385, F31 DA016457, DA020645] NR 46 TC 24 Z9 24 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 2008 VL 88 IS 3 BP 358 EP 365 DI 10.1016/j.pbb.2007.09.007 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 260RB UT WOS:000253026700021 PM 17905422 ER PT J AU He, YY Council, SE Feng, L Bonini, MG Chignell, CF AF He, Yu-Ying Council, Sarah E. Feng, Li Bonini, Marcelo G. Chignell, Colin F. TI Spatial distribution of protein damage by singlet oxygen in keratinocytes SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ROSE-BENGAL ACETATE; HYDROGEN-PEROXIDE; MOLECULAR-OXYGEN; CELLS; PHOTOSENSITIZATION; RADICALS; MITOCHONDRIA; GLUTATHIONE; APOPTOSIS; O-1(2) AB Singlet oxygen may be generated in cells by either endogenous or exogenous photosensitizers as a result of exposure to UV or visible irradiation. We have used immuno-spin trapping (Free Radic. Biol. Med. 36: 1214, 2004) to identify the subcellular targets of singlet oxygen generated by rose bengal (RB). Confocal fluorescence microscopy of HaCaT keratinocytes incubated with RB clearly showed that the dye entered the cells and was located mainly in the perinuclear region, probably associated with the Golgi apparatus and endoplasmic reticulum. Previous studies by Wright et al. (Free Radic. Biol. Med. 34: 637, 2003) have shown that long-lived protein hydroperoxides (POOH) are present in cells exposed to singlet oxygen-generating dyes. The addition of reducing metal ions such as Cu(+) to POOH results in the generation of protein-derived radicals, POO(center dot) and PO(center dot) which react with the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) to give relatively stable spin adducts. In order to determine the subcellular localization of the protein-DMPO adducts, we exposed keratinocytes to RB/light exposure and then incubated the cells with Cu+ and DMPO. After staining with antibody against DMPO followed by a secondary Alexa Fluor 488 goat anti-rabbit IgG, the intracellular distribution of protein-DMPO adducts was determined by confocal microscopy. The subcellular localization of the protein DMPO adducts was coincident with that of RB. This approach may provide information on the spatial distribution of singlet oxygen generated in cells. C1 [He, Yu-Ying; Council, Sarah E.; Feng, Li; Bonini, Marcelo G.; Chignell, Colin F.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM chignell@niehs.nih.gov FU Intramural NIH HHS [NIH0010085416, Z01 ES050046-29] NR 25 TC 16 Z9 16 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2008 VL 84 IS 1 BP 69 EP 74 DI 10.1111/j.1751-1097.2007.00199.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 253GO UT WOS:000252506900011 PM 18173704 ER PT J AU Wang, BD Strunnikov, A AF Wang, Bi-Dar Strunnikov, Alexander TI Transcriptional homogenization of rDNA repeats in the episome-based nucleolus induces genome-wide changes in the chromosomal distribution of condensin SO PLASMID LA English DT Article DE condensin; rDNA; episome; chromosome; chromatin; nucleolus; telomeres ID SACCHAROMYCES-CEREVISIAE; CHROMATID SEGREGATION; PROTEIN COMPLEXES; RIBOSOMAL DNA; ANAPHASE; ARCHITECTURE; DROSOPHILA; SUBUNITS; DISTINCT; MITOSIS AB Condensin activity establishes and maintains mitotic chromosome condensation, however the mechanisms of condensin recognition of specific chromosomal sites remain unknown. rDNA is the chief condensin binding locus in Saccharomyces cerevisiae, and the level of nucleolar transcription is one of the key factors determining condensin loading to the nucleolar organizer. A new aspect of this transcriptional control is demonstrated in cells with a diffuse (episomal) nucleolar organizer, where active transcription excludes condensin from the transcribed regions of rDNA. Genome-wide ChIP-chip analysis showed that these cells acquire an altered and a more robust pattern of chromosomal condensin distribution, with increased enrichment of wild-type hotspots and with emergence of new sites, most notably in the subtelomeric regions. This genome-wide condensin relocalization induced by the increase in rDNA transcription and, possibly, nucleolar architecture uncovers a novel potential role of the nucleolus in the general chromosome organization. Published by Elsevier Inc. C1 [Wang, Bi-Dar; Strunnikov, Alexander] NICHD, NIH, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Strunnikov, A (reprint author), NICHD, NIH, Lab Gene Regulat & Dev, 18T Library Dr,Room 106, Bethesda, MD 20892 USA. EM strunnik@mail.nih.gov OI Strunnikov, Alexander/0000-0002-9058-2256 FU Intramural NIH HHS [Z01 HD001903-11] NR 34 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0147-619X J9 PLASMID JI Plasmid PD JAN PY 2008 VL 59 IS 1 BP 45 EP 53 DI 10.1016/j.plasmid.2007.09.003 PG 9 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 261JG UT WOS:000253074300005 PM 18023874 ER PT J AU Simeonov, A Jadhav, A Sayed, AA Wang, YH Nelson, ME Thomas, CJ Inglese, J Williams, DL Austin, CP AF Simeonov, Anton Jadhav, Ajit Sayed, Ahmed A. Wang, Yuhong Nelson, Michael E. Thomas, Craig J. Inglese, James Williams, David L. Austin, Christopher P. TI Quantitative High-Throughput Screen Identifies Inhibitors of the Schistosoma mansoni Redox Cascade SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID THIOREDOXIN GLUTATHIONE-REDUCTASE; STATISTICAL PARAMETER; PRAZIQUANTEL; ASSAYS; PEROXIREDOXINS; PLATYHELMINTHS; SUSCEPTIBILITY; INFECTION; LIBRARIES; FUROXANS AB Schistosomiasis is a tropical disease associated with high morbidity and mortality, currently affecting over 200 million people worldwide. Praziquantel is the only drug used to treat the disease, and with its increased use the probability of developing drug resistance has grown significantly. The Schistosoma parasites can survive for up to decades in the human host due in part to a unique set of antioxidant enzymes that continuously degrade the reactive oxygen species produced by the host's innate immune response. Two principal components of this defense system have been recently identified in S. mansoni as thioredoxin/glutathione reductase (TGR) and peroxiredoxin (Prx) and as such these enzymes present attractive new targets for anti-schistosomiasis drug development. Inhibition of TGR/Prx activity was screened in a dual-enzyme format with reducing equivalents being transferred from NADPH to glutathione via a TGR-catalyzed reaction and then to hydrogen peroxide via a Prx-catalyzed step. A fully automated quantitative high-throughput (qHTS) experiment was performed against a collection of 71,028 compounds tested as 7- to 15-point concentration series at 5 mu L reaction volume in 1536-well plate format. In order to generate a robust data set and to minimize the effect of compound autofluorescence, apparent reaction rates derived from a kinetic read were utilized instead of end-point measurements. Actives identified from the screen, along with previously untested analogues, were subjected to confirmatory experiments using the screening assay and subsequently against the individual targets in secondary assays. Several novel active series were identified which inhibited TGR at a range of potencies, with IC(50)s ranging from micromolar to the assay response limit (similar to 25 nM). This is, to our knowledge, the first report of a large-scale HTS to identify lead compounds for a helminthic disease, and provides a paradigm that can be used to jump-start development of novel therapeutics for other neglected tropical diseases. C1 [Simeonov, Anton; Jadhav, Ajit; Wang, Yuhong; Nelson, Michael E.; Thomas, Craig J.; Inglese, James; Austin, Christopher P.] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Sayed, Ahmed A.; Williams, David L.] Illinois State Univ, Dept Biol Sci, Normal, IL 61761 USA. RP Simeonov, A (reprint author), NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. EM dlwilli@ilstu.edu; austinc@mail.nih.gov FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research; Intramural Research Program of the NHGRI; NIH; NIH/NIMH [1R03MH076449] FX This research was supported by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research and the Intramural Research Program of the NHGRI, NIH, and in part by NIH/NIMH grant 1R03MH076449 (DLW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 64 Z9 66 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2008 VL 2 IS 1 AR e127 DI 10.1371/journal.pntd.0000127 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 385HX UT WOS:000261806400014 PM 18235848 ER PT J AU Nielsen, KLC Hill, DJT Watson, KA Connell, JW Ikeda, S Kudo, H Whittaker, AK AF Nielsen, Kresten L. C. Hill, David J-T. Watson, Kent A. Connell, John W. Ikeda, Shigetoshi Kudo, Hisaaki Whittaker, Andrew K. TI The radiation degradation of a nanotube-polyimide nanocomposite SO POLYMER DEGRADATION AND STABILITY LA English DT Article DE SWNT; carbon nanotubes; polyimide; LaRC CP-2; tensile; UV-Vis spectroscopy ID WALL CARBON NANOTUBES; ELECTROSTATIC CHARGE MITIGATION; IONIZING-RADIATION; POLYMER COMPOSITES; GAMMA-RADIATION; FILMS; SPECTROSCOPY; DISPERSION; PROTON AB The radiation degradation of a nanotube-polyimide nanocomposite was studied. Radiation chemistry was observed that was not present in the unmodified polymer or in the imbedded single-walled carbon nanotubes (SWNTs) themselves. The tensile properties were found to be improved by the addition of SWNTs in the unirradiated materials, and no deterioration in these properties with irradiation was observed. The SWNTs were found to have a detrimental effect on the optical properties however. The transparency of the composite was degraded significantly faster by electron-beam radiation than the neat polymer was. This may make the SWNT/polyimide composites unsuitable for some space applications. Electron Spin Resonance (ESR) measurements determined that the SWNTs interfere with the radical chemistry in the irradiated materials. This could be due to energy dissipation by the SWNT network, preventing the formation of radical species, or alternatively, preferential reaction or termination of radicals by the nanotubes. FT-Raman spectroscopy was found to be a very useful tool for examining SWNTs embedded at low concentrations. It revealed no signs of SWNT degradation up to 10 MGy. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Nielsen, Kresten L. C.; Hill, David J-T.; Whittaker, Andrew K.] Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia. [Nielsen, Kresten L. C.; Hill, David J-T.; Whittaker, Andrew K.] Univ Queensland, Ctr Magnet Resonance, Brisbane, Qld 4072, Australia. [Watson, Kent A.] NIA, Hampton, VA 23666 USA. [Connell, John W.] NASA, Langley Res Ctr, Hampton, VA 23681 USA. [Ikeda, Shigetoshi; Kudo, Hisaaki] Univ Tokyo, Nucl Professional Sch, Tokai, Ibaraki 3191188, Japan. RP Whittaker, AK (reprint author), Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia. EM andrew.whittaker@cmr.uq.edu.au RI Nielsen, Kres/M-8962-2015; Whittaker, Andrew/E-6172-2011 OI Nielsen, Kres/0000-0001-6375-684X; Whittaker, Andrew/0000-0002-1948-8355 NR 36 TC 18 Z9 18 U1 1 U2 24 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0141-3910 J9 POLYM DEGRAD STABIL JI Polym. Degrad. Stabil. PD JAN PY 2008 VL 93 IS 1 BP 169 EP 175 DI 10.1016/j.polymdegradstab.2007.10.010 PG 7 WC Polymer Science SC Polymer Science GA 264RB UT WOS:000253305500021 ER PT J AU Rao, SS Kong, WP Wei, CJ Perez, D Styles, DK Yang, ZZ Murray, C Ault, A Andrews, C Nabel, GJ AF Rao, S. S. Kong, W. -P. Wei, C. -J. Perez, D. Styles, D. K. Yang, Z. Z. Murray, C. Ault, A. Andrews, C. Nabel, G. J. TI A gene-based avian influenza vaccine SO POULTRY SCIENCE LA English DT Meeting Abstract DE avian influenza; gene-based vaccine; poultry C1 [Rao, S. S.; Kong, W. -P.; Wei, C. -J.; Yang, Z. Z.; Murray, C.; Ault, A.; Andrews, C.; Nabel, G. J.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Perez, D.] Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PY 2008 VL 87 BP 2 EP 2 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA 409XH UT WOS:000263538600005 ER PT J AU Post, DJ AF Post, D. J. TI CEIRSSurveillance efforts through the NIAID Influenza Centers of Excellence (CEIRS) and resources available to the scientific community SO POULTRY SCIENCE LA English DT Meeting Abstract DE influenza; surveillance; CEIRS C1 [Post, D. J.] NIAID, DMID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PY 2008 VL 87 BP 3 EP 3 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA 409XH UT WOS:000263538600009 ER PT J AU Herzlich, AA Tuo, JS Chan, CC AF Herzlich, Alexandra A. Tuo, Jingsheng Chan, Chi-Chao TI Peroxisome Proliferator-Activated Receptor and Age-Related Macular Degeneration SO PPAR RESEARCH LA English DT Review AB Age-related macular degeneration (AMD) is the leading cause of new blindness in the western world and is becoming more of a socio-medical problem as the proportion of the aged population increases. There are multiple efforts underway to better understand this disease process. AMD involves the abnormal retinal pigment epithelium (RPE), drusen formation, photoreceptor atrophy, and choroidal neovascularization. Peroxisome proliferator-activated receptors (PPARs) play an important role in lipid degeneration, immune regulation, regulation of reactive oxygen species (ROSs), as well as regulation of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and docosahexaenoic acid (DHA). These molecules have all been implicated in the pathogenesis of AMD. In addition, PPAR gamma is expressed in RPE, an essential cell in photoreceptor regeneration and vision maintenance. This review summarizes the interactions between PPAR, AMD-related molecules, and AMD-related disease processes. Copyright (C) 2008 Alexandra A. Herzlich et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. C1 [Herzlich, Alexandra A.; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 NR 116 TC 18 Z9 18 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2008 AR 389507 DI 10.1155/2008/389507 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V13ZA UT WOS:000207703500001 ER PT J AU Phang, JM Pandhare, J Zabirnyk, O Liu, YM AF Phang, James M. Pandhare, Jui Zabirnyk, Olga Liu, Yongmin TI PPAR gamma and Proline Oxidase in Cancer SO PPAR RESEARCH LA English DT Review AB Proline is metabolized by its own specialized enzymes with their own tissue and subcellular localizations and mechanisms of regulation. The central enzyme in this metabolic system is proline oxidase, a flavin adenine dinucleotide-containing enzyme which is tightly bound to mitochondrial inner membranes. The electrons from proline can be used to generate ATP or can directly reduce oxygen to form superoxide. Although proline may be derived from the diet and biosynthesized endogenously, an important source in the microenvironment is from degradation of extracellular matrix by matrix metalloproteinases. Previous studies showed that proline oxidase is a p53-induced gene and its overexpression can initiate proline-dependent apoptosis by both intrinsic and extrinsic pathways. Another important factor regulating proline oxidase is peroxisome proliferator activated receptor gamma (PPAR gamma). Importantly, in several cancer cells, proline oxidase may be an important mediator of the PPAR gamma-stimulated generation of ROS and induction of apoptosis. Knockdown of proline oxidase expression by antisense RNA markedly decreased these PPAR gamma-stimulated effects. These findings suggest an important role in the proposed antitumor effects of PPAR gamma. Moreover, it is possible that proline oxidase may contribute to the other metabolic effects of PPAR gamma. Copyright (C) 2008 James M. Phang et al. C1 [Phang, James M.; Pandhare, Jui; Zabirnyk, Olga] NCI, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Liu, Yongmin] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. RP Phang, JM (reprint author), NCI, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM phang@mail.ncifcrf.gov FU NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [N01-CO-12400] FX This research is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project also has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health under Contract no. N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 68 TC 9 Z9 9 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2008 AR 542694 DI 10.1155/2008/542694 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V13WZ UT WOS:000207698200001 ER PT J AU Yang, XY Wang, LH Farrar, WL AF Yang, Xiao Yi Wang, Li Hua Farrar, William L. TI A Role for PPAR gamma in the Regulation of Cytokines in Immune Cells and Cancer SO PPAR RESEARCH LA English DT Review AB Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. PPAR. and its ligands appear to serve diverse biological functions. In addition to the well-studied effects of PPAR. on metabolism and cellular differentiation, abundant evidence suggests that PPAR. is an important regulator of the immune system and cancers. Since cytokines are not only key modulators of inflammation with pro-and anti-inflammatory functions but they also can either stimulate or inhibit tumor growth and progression, this review summarizes the role for PPAR. in the regulation of cytokine production and cytokine-mediated signal transduction pathways in immune cells and cancer. Copyright (C) 2008 Xiao Yi Yang et al. C1 [Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Div Basic Sci, Frederick, MD 21702 USA. [Yang, Xiao Yi; Wang, Li Hua] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. RP Farrar, WL (reprint author), NCI, Canc Stem Cell Sect, Lab Canc Prevent, Div Basic Sci, Frederick, MD 21702 USA. EM farrar@ncifcrf.gov FU NCI/NIH [NO1-CO-12400] FX This project has been funded in whole or in part with Federal funds from the NCI/NIH under Contract NO1-CO-12400. NR 112 TC 5 Z9 5 U1 1 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2008 AR 961753 DI 10.1155/2008/961753 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V13YH UT WOS:000207701600001 ER PT B AU Newman, DJ Cragg, GM Kingston, DGI AF Newman, David J. Cragg, Gordon M. Kingston, David G. I. BE Wermuth, CG TI Natural Products as Pharmaceuticals and Sources for Lead Structures SO PRACTICE OF MEDICINAL CHEMISTRY, 3RD EDITION LA English DT Article; Book Chapter ID BIOSYNTHETIC GENE-CLUSTER; MICROTUBULE-STABILIZING AGENTS; SPONGE KIRKPATRICKIA-VARIALOSA; ANGIOTENSIN-CONVERTING ENZYME; SOLID-PHASE SYNTHESIS; ANTI-HIV AGENTS; DRUG DISCOVERY; ENDOPHYTIC FUNGUS; COMBINATORIAL LIBRARIES; BIOLOGICAL EVALUATION C1 [Newman, David J.; Cragg, Gordon M.] NCI, Nat Prod Branch, Frederick, MD 21701 USA. [Kingston, David G. I.] Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. RP Newman, DJ (reprint author), NCI, Nat Prod Branch, 1003 W 7th St,Suite 206, Frederick, MD 21701 USA. RI Kingston, David/B-4272-2009 OI Kingston, David/0000-0001-8944-246X NR 235 TC 2 Z9 4 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056877-5; 978-0-12-374194-3 PY 2008 BP 159 EP 186 DI 10.1016/B978-0-12-374194-3.00008-1 PG 28 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA BCS40 UT WOS:000311276600011 ER PT B AU Langer, T Bryant, SD AF Langer, Thierry Bryant, Sharon D. BE Wermuth, CG TI In Silico Screening: Hit Finding from Database Mining SO PRACTICE OF MEDICINAL CHEMISTRY, 3RD EDITION LA English DT Article; Book Chapter ID COMBINATORIAL LIBRARY DESIGN; MOLECULAR DIVERSITY ANALYSIS; BOUND LIGAND CONFORMATIONS; RATIONAL DRUG DESIGN; HIGH-THROUGHPUT; GENETIC ALGORITHM; PHARMACOPHORE MODEL; MULTIOBJECTIVE OPTIMIZATION; INCREMENTAL CONSTRUCTION; HISTORICAL-PERSPECTIVE C1 [Langer, Thierry] Inte Ligand GmbH, A-2344 Maria Enzersdorf, Austria. [Bryant, Sharon D.] NIEHS, Med Chem Grp, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Langer, T (reprint author), Inte Ligand GmbH, Clemens Maria Hofbauer G6, A-2344 Maria Enzersdorf, Austria. NR 184 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056877-5; 978-0-12-374194-3 PY 2008 BP 210 EP 227 DI 10.1016/B978-0-12-374194-3.00010-X PG 18 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA BCS40 UT WOS:000311276600013 ER PT J AU Langer, T Bryant, SD AF Langer, Thierry Bryant, Sharon D. BE Wermuth, CG TI 3D Quantitative Structure-Property Relationships SO PRACTICE OF MEDICINAL CHEMISTRY, 3RD EDITION LA English DT Article; Book Chapter ID GRID-INDEPENDENT DESCRIPTORS; MULTIVARIATE DATA-ANALYSIS; MOLECULAR-FIELD ANALYSIS; BOUND LIGAND CONFORMATIONS; ACETYLCHOLINESTERASE INHIBITORS; DRUG MOLECULES; SIMILARITY DETERMINATION; PRINCIPAL PROPERTIES; IN-SILICO; QSAR C1 [Langer, Thierry] Inte Ligand GmbH, A-2344 Maria Enzersdorf, Austria. [Bryant, Sharon D.] NIEHS, Med Chem Grp, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Langer, T (reprint author), Inte Ligand GmbH, Clemens Maria Hofbauer G-6, A-2344 Maria Enzersdorf, Austria. NR 118 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056877-5 PY 2008 BP 587 EP 604 DI 10.1016/B978-0-12-374194-3.00029-9 PG 18 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA BCS40 UT WOS:000311276600032 ER PT J AU Bader, JL Nemhauser, J Chang, F Mashayekhi, B Sczcur, M Knebel, A Hrdina, C Coleman, N AF Bader, Judith L. Nemhauser, Jeffrey Chang, Florence Mashayekhi, Bijan Sczcur, Marti Knebel, Ann Hrdina, Chad Coleman, Norman TI Radiation event medical management (REMM): Website guidance for health care providers SO PREHOSPITAL EMERGENCY CARE LA English DT Article DE radiological event; nuclear event; terrorism; improvised nuclear device; radiological dispersal device; acute radiation syndrome; medical countermeasures; radiation exposure; radiation contamination; biodosimetry AB Planning for and exercising the medical response to potential chemical, biological, radiological, nuclear, and explosive (CBRNE) terrorist events are new responsibilities for most health care providers. Among potential CBRNE events, radiological and/or nuclear (rad/nuc) events are thought to have received the least attention from health care providers and planners. To assist clinicians, the U.S. Department of Health and Human Services (HHS) has created a new, innovative tool kit, the Radiation Event Medical Management (REMM) web portal (http://remm.nlm.gov). Goals of REMM include providing (1) algorithm-style, evidence-based, guidance about clinical diagnosis and treatment during mass casualty rad/nuc events; (2) just-in-time, peer-reviewed, usable information supported by sufficient background material and context to make complex diagnosis and management issues understandable to those without formal radiation medicine expertise; (3) a zip-file of complete web portal files downloadable in advance so the site would be available offline without an Internet connection; (4) a concise collection of the printable, key documents that can be taken into the field during an event; (5) a framework for medical teams and individuals to initiate rad/nuc planning and training; and (6) an extensive bibliography of key, peer-reviewed, and official guidance documents relevant to rad/nuc responses. Since its launch, REMM has been well received by individual responders and teams across the country and internationally. It has been accessed extensively, particularly during training exercises. Regular content updates and addition of new features are ongoing. The article reviews the development of REMM and some of its key content areas, features, and plans for future development. C1 [Bader, Judith L.; Coleman, Norman] NCI, NIH, Bethesda, MD 20892 USA. [Nemhauser, Jeffrey] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Radiat Studies Branch, Atlanta, GA 30333 USA. [Chang, Florence; Mashayekhi, Bijan; Sczcur, Marti] Natl Lib Med, NIH, Specialized Informat Syst Div, Bethesda, MD 20892 USA. [Bader, Judith L.; Knebel, Ann; Hrdina, Chad; Coleman, Norman] US Dept HHS, Off Assistant Secretary Preparedness & Response, Off Preparedness & Emergency Operat, Washington, DC USA. RP Bader, JL (reprint author), 6116 Execut Blvd,Suite 300, Rockville, MD 20852 USA. EM jbader@mail.nih.gov NR 18 TC 13 Z9 14 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1090-3127 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PY 2008 VL 12 IS 1 BP 1 EP 11 DI 10.1080/10903120701710595 PG 11 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA 251CB UT WOS:000252347100001 PM 18189170 ER PT J AU Robey, PG AF Robey, Pamela Gehron BE Bilezikian, JP Raisz, LG Martin, TJ TI Noncollagenous Bone Matrix Proteins SO PRINCIPLES OF BONE BIOLOGY, VOL 1, 3RD EDITION LA English DT Article; Book Chapter ID LINKED GLYCOPROTEINS SIBLINGS; GAMMA-CARBOXYGLUTAMIC ACID; RICH REPEAT PROTEINS; TARGETED DISRUPTION; GLA PROTEIN; EXTRACELLULAR-MATRIX; DEFICIENT MICE; AGGRECAN GENE; SMALL PROTEOGLYCANS; MOLECULAR-CLONING C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Robey, PG (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 92 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056875-1 PY 2008 BP 335 EP 349 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BCS73 UT WOS:000311294700020 ER PT J AU Brandi, ML Bordi, C Tonelli, F Falchetti, A Marx, SJ AF Brandi, Maria Luisa Bordi, Cesare Tonelli, Francesco Falchetti, Alberto Marx, Stephen J. BE Bilezikian, JP Raisz, LG Martin, TJ TI Multiple Endocrine Neoplasia Type 1 SO PRINCIPLES OF BONE BIOLOGY, VOL 2, 3RD EDITION LA English DT Article; Book Chapter ID ZOLLINGER-ELLISON-SYNDROME; FAMILIAL ISOLATED HYPERPARATHYROIDISM; TUMOR-SUPPRESSOR MENIN; PRIMARY PARATHYROID HYPERPLASIA; GASTRIC CARCINOID-TUMORS; FIBROBLAST-GROWTH-FACTOR; GERM-LINE MUTATIONS; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; HISTONE METHYLTRANSFERASE COMPLEX; DEPENDENT KINASE INHIBITORS C1 [Brandi, Maria Luisa; Falchetti, Alberto] Univ Florence, Dept Internal Med, Azienda Osped Univ Careggi, I-650139 Florence, Italy. [Brandi, Maria Luisa; Falchetti, Alberto] Univ Florence, Reg Ctr Hereditary Endocrine Tumors, Azienda Osped Univ Careggi, I-650139 Florence, Italy. [Bordi, Cesare] Univ Parma, Dept Pathol & Lab Med, Sect Anat Pathol, I-143100 Parma, Italy. [Tonelli, Francesco] Univ Florence, Surg Unit, Dept Clin Physiopathol, I-650139 Florence, Italy. [Marx, Stephen J.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Brandi, ML (reprint author), Univ Florence, Dept Internal Med, Azienda Osped Univ Careggi, I-650139 Florence, Italy. RI FALCHETTI, ALBERTO/Q-1787-2016 OI FALCHETTI, ALBERTO/0000-0002-6739-4417 NR 282 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056875-1 PY 2008 BP 1345 EP 1374 DI 10.1016/B978-0-12-373884-4.00075-6 PG 30 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BCS75 UT WOS:000311296900021 ER PT B AU Weinstein, LS Collins, MT AF Weinstein, Lee S. Collins, Michael T. BE Bilezikian, JP Raisz, LG Martin, TJ TI Diseases Resulting from Defects in the G Protein G(s)alpha SO PRINCIPLES OF BONE BIOLOGY, VOL 2, 3RD EDITION LA English DT Article; Book Chapter ID ALBRIGHT-HEREDITARY-OSTEODYSTROPHY; STIMULATORY-G-PROTEIN; PSEUDOHYPOPARATHYROIDISM-TYPE-IB; GUANINE-NUCLEOTIDE-BINDING; XL-ALPHA-S; POLYOSTOTIC FIBROUS DYSPLASIA; PROGRESSIVE OSSEOUS HETEROPLASIA; CYCLASE COUPLING PROTEIN; RECEPTOR-MEDIATED ACTIVATION; HUMAN GNAS1 GENE C1 [Weinstein, Lee S.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov NR 309 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056875-1; 978-0-12-373884-4 PY 2008 BP 1453 EP 1477 DI 10.1016/B978-0-12-373884-4.00018-5 PG 25 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BCS75 UT WOS:000311296900026 ER PT B AU Zhang, L Zhang, JQ Zhou, XB Wang, HH Huang, YF Liu, H Wong, S AF Zhang, Lin Zhang, Jian-Qiu Zhou, Xiao-Bo Wang, Hong-Hui Huang, Yu-Fei Liu, Hui Wong, Stephen GP IEEE TI Feature selection and classification of pro-TOF data based on soft information SO PROCEEDINGS OF 2008 INTERNATIONAL CONFERENCE ON MACHINE LEARNING AND CYBERNETICS, VOLS 1-7 LA English DT Proceedings Paper CT 7th International Conference on Machine Learning and Cybernetics CY JUL 12-15, 2008 CL Kunming, PEOPLES R CHINA SP Hebei Univ, IEEE Syst, Man & Cybernet Soc, Yunnan Univ, Machine Learning & Cybernet Res Inst AB In this paper, we introduce a feature selection and classification method for prOTOF Mass Spectrometry (MS) data profiles of diseased and healthy patients. The method is based on a special statistical measure, which quantifies the probability of the existence of peptidepeaks. A special ranking score that is based on the statistical measure is used for selecting features that can best distinguish diseased and healthy data profiles. Based on the selected features, we applied a variety of classification algorithms and the results are compared with that of a method which selects features only based on peak heights. The results show a significant improvement in classification error rate with our proposed method. C1 [Zhang, Lin; Liu, Hui] China Univ Min & Technol, Sch Informat & Elect Engn, Xuzhou 221008, Peoples R China. [Zhang, Jian-Qiu; Huang, Yu-Fei] Univ Texas San Antonio, Dept Elect & Comp Engn, San Antonio, TX 78249 USA. [Zhou, Xiao-Bo; Wong, Stephen] Texas Methodist Hosp Res Inst, Houston, TX 77030 USA. [Wang, Hong-Hui] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. [Huang, Yu-Fei] Univ Texas San Antonio, Dept Bioengn, San Antonio, TX 78249 USA. [Huang, Yu-Fei] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Huang, Yu-Fei] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. RP Zhang, L (reprint author), China Univ Min & Technol, Sch Informat & Elect Engn, Xuzhou 221008, Peoples R China. EM michelle.zhang@utsa.edu; xiaobo.zhou@tmhs.org FU Methodist Hospital Scholarship; NIH [R01LM08696, R01LM009161, R01AG028928]; NSF [CCF-0546345]; Chinese Scholarship Council FX The authors will thank Dr. Lisa Sapp in PerkinElmer (Boston MA) for acquiring all prOTOF MS data. Dr. Zhou is partially funded by The Methodist Hospital Scholarship Award. He and Dr Wong are also partially funded by NIH grants R01LM08696, R01LM009161, and R01AG028928. Y. Huang is supported by an NSF Grant CCF-0546345. MS. L. Zhang and H. Liu are supported by the Chinese Scholarship Council. NR 6 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-2095-7 PY 2008 BP 4018 EP + DI 10.1109/ICMLC.2008.4621105 PG 2 WC Computer Science, Cybernetics; Engineering, Electrical & Electronic; Robotics SC Computer Science; Engineering; Robotics GA BII01 UT WOS:000259604902171 ER PT B AU Liu, HC Yih, JM Wu, DB Liu, SW AF Liu, Hsiang-Chuan Yih, Jeng-Ming Wu, Der-Bang Liu, Shin-Wu GP IEEE TI FUZZY POSSIBILITY C-MEAN CLUSTERING ALGORITHMS BASED ON COMPLETE MAHALANOBIS DISTANCES SO PROCEEDINGS OF 2008 INTERNATIONAL CONFERENCE ON WAVELET ANALYSIS AND PATTERN RECOGNITION, VOLS 1 AND 2 SE International Conference on Wavelet Analysis and Pattern Recognition LA English DT Proceedings Paper CT 6th International Conference on Wavelet Analysis and Pattern Recognition CY AUG 30-31, 2008 CL Hong Kong, PEOPLES R CHINA SP Hebei Univ, IEEE Syst, Man & Cybernet Soc, Chongqing Univ, Hong Kong Baptist Univ DE FCM; CM; FCM-M; PCM-M; FPCM-CM AB Two well known fuzzy partition clustering algorithms, FCM and FPCM are based on Euclidean distance function, which can only be used to detect spherical structural clusters. GK clustering algorithm and GG clustering algorithm, were developed to detect non-spherical structural clusters, but both of them fail to consider the relationships between cluster centers in the objective function, needing additional prior information.. In our previous studies, we developed two improved algorithms, FCM-M and FPCM-M, based on unsupervised Mahalanobis distance without any additional prior information. And FPCM-M is better than FCM-M, since the former has the more information about the typicalities than the later. In this paper, an improved new unsupervised algorithm, "fuzzy possibility c-mean based on complete Mahalanobis distance without any prior information (FPCM-CM)", is proposed. In our new algorithm, not only the local covariance matrix of each cluster but also the overall covariance matrix was considered. It can get more information and higher accuracy by considering the additional overall covariance matrix than FPCM-M. A real data set was applied to prove that the performance of the FPCM-CM algorithm is better than those of the traditional FCM and FPCM algorithm and our previous FCM-M. C1 [Liu, Hsiang-Chuan] Asia Univ, Dept Bioinformat, Taichung, Taiwan. [Yih, Jeng-Ming] Taichung Univ, Grad Inst Educ Measurement, Taichung, Taiwan. [Wu, Der-Bang] Taichung Univ, Dept Math Educ, Taichung, Taiwan. [Liu, Shin-Wu] Natl Inst Hlth, NIAID, Bethesda, MD 20892 USA. RP Liu, HC (reprint author), Asia Univ, Dept Bioinformat, Taichung, Taiwan. EM lhc@asia.edu.tw; yih@mail.ntcu.edu.tw; wudb@hotmail.com; fpan0366@yahoo.com.tw FU National Science Council [96-2413--H-468-001] FX This paper is partially supported by the National Science Council grant (NSC 96-2413--H-468-001). NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-2238-8 J9 INT C WAVEL ANAL PAT PY 2008 BP 50 EP + DI 10.1109/ICWAPR.2008.4635749 PG 3 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BIJ92 UT WOS:000260168200010 ER PT B AU Liu, HC Liu, SW Chang, PC Huang, WC Liao, CH AF Liu, Hsiang-Chuan Liu, Shin-Wu Chang, Pei-Chun Huang, Wen-Chun Liao, Chien-Hsiung GP IEEE TI A NOVEL CLASSIFIER FOR INFLUENZA A VIRUSES BASED ON SVM AND LOGISTIC REGRESSION SO PROCEEDINGS OF 2008 INTERNATIONAL CONFERENCE ON WAVELET ANALYSIS AND PATTERN RECOGNITION, VOLS 1 AND 2 SE International Conference on Wavelet Analysis and Pattern Recognition LA English DT Proceedings Paper CT 6th International Conference on Wavelet Analysis and Pattern Recognition CY AUG 30-31, 2008 CL Hong Kong, PEOPLES R CHINA SP Hebei Univ, IEEE Syst, Man & Cybernet Soc, Chongqing Univ, Hong Kong Baptist Univ DE Influenza A viruses; Hurst exponent; SVM; Logistic regression; SVM-Logistic regression AB In search of good classifier of hosts of influenza A viruses is an important issue to prevent pandemic flu. The hemagglutinin protein in the virus genome is the major molecule that determining the range of hosts. In this paper, a novel classification algorithm of hemagglutinin proteins integrating SVM and logistic regression based on 4 kinds of Hurst exponents for each protein sequence is proposed. This method not used before is the first one integrating the physicochemical properties, fractal property, SVM and logistic regression classifier. For evaluating the performance of this new algorithm, a real data experiment by using 5-fold Cross-Validation accuracy is conducted. Experimental result shows that this new classification algorithm is useful and batter than SVM and logistic regression, respectively.. C1 [Liu, Hsiang-Chuan; Chang, Pei-Chun; Liao, Chien-Hsiung] Asia Univ, Dept Bioinformat, Taichung, Taiwan. [Liu, Shin-Wu] Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Bethesda, MD USA. [Huang, Wen-Chun] Taichung Univ, Grad Inst Educ Measurement & Stat, Taichung, Taiwan. RP Liu, HC (reprint author), Asia Univ, Dept Bioinformat, Taichung, Taiwan. EM lhc@asia.edu.tw; liushin@mail.nih.gov; pcchang@asia.edu.tw; huang.hwc@gmail.com; ace.liao@gmail.com FU National Science Council [96-2413--H-468-001] FX This paper is partially supported by the National Science Council grant (NSC 96-2413--H-468-001). NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-2238-8 J9 INT C WAVEL ANAL PAT PY 2008 BP 287 EP + DI 10.1109/ICWAPR.2008.4635791 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BIJ92 UT WOS:000260168200052 ER PT B AU Agarwal, SK Ozawa, A Rice, TS Burns, AL Mateo, C Cochran, C Simonds, WF Libutti, SK Kaur, S Chandrasekharappa, SC Marx, SJ AF Agarwal, S. K. Ozawa, A. Rice, T. S. Burns, A. L. Mateo, C. Cochran, C. Simonds, W. F. Libutti, S. K. Kaur, S. Chandrasekharappa, S. C. Marx, S. J. BE GodoyMatos, A Wass, J TI Hyperparathyroidism and MEN1 SO PROCEEDINGS OF THE 13TH INTERNATIONAL CONGRESS OF ENDOCRINOLOGY LA English DT Proceedings Paper CT 13th International Congress of Endocrinology CY NOV 08-12, 2008 CL Rio de Janeiro, BRAZIL ID FAMILIAL ISOLATED HYPERPARATHYROIDISM; MULTIPLE ENDOCRINE NEOPLASIA; JAW TUMOR SYNDROME; KINASE INHIBITORS; MUTATIONS; TYPE-1; HRPT2; GENE; DRUGS; CELLS AB Most hyperparathyroid (HPT) states are initiated by a germline or somatic gene mutation. The analysis of hereditary HPT, such as multiple endocrine neoplasia type 1 (MEN1), has uncovered most of the major genes involved in hereditary and even some in non-hereditary HPT. Knowledge about a mutated HPT gene or about other clinical details helps predict important clinical features of its HPT syndrome. This in turn helps to plan special managements, including development of useful drugs. For example, identification of the MEN1 gene has helped clarify the rare MEN1 tumors as well as this gene's role in many common endocrine tumors. C1 [Agarwal, S. K.; Ozawa, A.; Rice, T. S.; Burns, A. L.; Mateo, C.; Cochran, C.; Simonds, W. F.; Marx, S. J.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Agarwal, SK (reprint author), NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NR 25 TC 0 Z9 0 U1 0 U2 1 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-472-8 PY 2008 BP 101 EP 107 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BIY34 UT WOS:000263685200018 ER PT B AU Ma, X Idle, JR Gonzalez, FJ AF Ma, X. Idle, J. R. Gonzalez, F. J. BE Kaminsky, LS TI Defining the Role of Pregnane X Receptor in vivo Using Genetically Engineered Mouse Models SO PROCEEDINGS OF THE 17TH INTERNATIONAL SYMPOSIUM ON MICROSOMES AND DRUG OXIDATIONS LA English DT Proceedings Paper CT 17th International Symposium on Microsomes and Drug Oxidations CY JUL 06-10, 2008 CL Saratoga Springs, NY AB The pregnane X receptor (PXR, NRII2), a member of the nuclear receptor superfamily, regulates a large network of genes including those encoding metabolic enzymes and transporters (1). While considerable work has been done in characterizing PXR using Cultured cells and transfection studies, genetically engineered PXR mouse models have led to the study of human PXR function in whole animals. PXR-humanized mouse models serve to overcome the species differences in response to PXR ligands. These mice respond to known human PXR ligands Such as rifampicin and can thus can serve to predict human response to drugs that activate PXR and to investigate possible drug-drug interactions involving the PXR target gene CYP3A4. C1 [Ma, X.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-476-6 PY 2008 BP 19 EP 23 PG 5 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Pharmacology & Pharmacy GA BIZ61 UT WOS:000263985900004 ER PT S AU Antani, SL Thoma, GR AF Antani, Sameer L. Thoma, George R. BE Puuronen, S Pechenizkiy, M Tsymbal, A Lee, DJ TI Bridging the gap: Enabling CBIR in medical applications SO PROCEEDINGS OF THE 21ST IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE COMPUTER-BASED MEDICAL SYSTEMS : PROCEEDINGS OF THE ANNUAL IEEE SYMPOSIUM LA English DT Proceedings Paper CT 21st IEEE International Symposium on Computer-Based Medical Systems CY JUN 17-19, 2008 CL Jyvaskyla, FINLAND SP IEEE Comp Soc, TCCM, Univ Jyvaskyla, Dept Comp Sci & Informat Syst, ACM SIGAPP AB Content-based Image Retrieval (CBIR) for medical images has received a significant research interest over the past decade as a promising approach to address the data management challenges posed by the rapidly increasing volume of medical image data in use. Articles published in the literature detail the benefits and present impressive results to substantiate potential impact of the technology. However, the benefits have yet to make it to mainstream clinical, biomedical research, or educational use. No major commercial software tools are available for use in medical imaging products, although several are available for commercial stock photo collections. CBIR has had some success in isolated instances in applications on limited data sets addressing specialized medical problems and at biomedical research laboratories and hospitals that are tightly coupled with software developers. This article explores some possible causes of this "gap" in the lack of translation of research into widespread biomedical use and provides some directions to alleviate the problem. C1 [Antani, Sameer L.; Thoma, George R.] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Antani, SL (reprint author), NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 2 TC 5 Z9 6 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1063-7125 BN 978-0-7695-3165-6 J9 COMP MED SY PY 2008 BP 4 EP 6 DI 10.1109/CBMS.2008.133 PG 3 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Biomedical; Mathematical & Computational Biology SC Computer Science; Engineering; Mathematical & Computational Biology GA BHZ14 UT WOS:000257577600001 ER PT S AU Zhu, Y Huang, X Lopresti, D Long, R Antani, S Xue, Z Thoma, G AF Zhu, Yaoyao Huang, Xiaolei Lopresti, Daniel Long, Rodeny Antani, Sameer Xue, Zhiyun Thoma, George BE Puuronen, S Pechenizkiy, M Tsymbal, A Lee, DJ TI Web-based multi-observer segmentation evaluation tool SO PROCEEDINGS OF THE 21ST IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 21st IEEE International Symposium on Computer-Based Medical Systems CY JUN 17-19, 2008 CL Jyvaskyla, FINLAND SP IEEE Comp Soc, TCCM, Univ Jyvaskyla, Dept Comp Sci & Informat Syst, ACM SIGAPP AB Multi-observer segmentation evaluation is useful in the imaging community. We have developed web-based software for automatic performance evaluation of multiple image segmentations which is based on the Baysian Decision framework. It computes a probabilistic estimate of the true segmentation(ground truth map) and performance measures for the individual segmentations (sensitivity and specificity). The strength of the tool is that it integrates the two kinds of prior knowledge of segmentations: the truth prior (the prior probability) and the observer prior (the performance measures of observers), which can generate more accurate evaluations. C1 [Zhu, Yaoyao; Huang, Xiaolei; Lopresti, Daniel] Lehigh Univ, Dept Comp Sci & Engn, Bethlehem, PA 18015 USA. [Long, Rodeny; Antani, Sameer; Xue, Zhiyun; Thoma, George] Natl Lib Med, Natl Inst Hlth, Bethesda, MD 20894 USA. RP Zhu, Y (reprint author), Lehigh Univ, Dept Comp Sci & Engn, Bethlehem, PA 18015 USA. EM yaz304@lehigh.edu; xih206@lehigh.edu; dal9@lehigh.edu; rlong@mail.nih.gov; santani@mail.nih.gov; xuez@mail.nih.gov; gthoma@mail.nih.gov OI Antani, Sameer/0000-0002-0040-1387 NR 4 TC 1 Z9 1 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2372-9198 BN 978-0-7695-3165-6 J9 COMP MED SY PY 2008 BP 167 EP + DI 10.1109/CBMS.2008.121 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Biomedical; Mathematical & Computational Biology SC Computer Science; Engineering; Mathematical & Computational Biology GA BHZ14 UT WOS:000257577600035 ER PT S AU Chang, YC Antani, S Lee, DJ Gledhill, K Long, LR Christensen, P AF Chang, Yuchou Antani, Sarneer Lee, Dah-Jye Gledhill, Kent Long, L. Rodney Christensen, Paul BE Puuronen, S Pechenizkiy, M Tsymbal, A Lee, DJ TI CBIR of spine X-ray images on inter-vertebral disc space and shape profiles SO PROCEEDINGS OF THE 21ST IEEE INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS SE IEEE International Symposium on Computer-Based Medical Systems LA English DT Proceedings Paper CT 21st IEEE International Symposium on Computer-Based Medical Systems CY JUN 17-19, 2008 CL Jyvaskyla, FINLAND SP IEEE Comp Soc, TCCM, Univ Jyvaskyla, Dept Comp Sci & Informat Syst, ACM SIGAPP ID RETRIEVAL AB There is very limited research published in the literature that applies content-based image retrieval (CBIR) techniques to retrieval of digitized spine X-ray images using a combination of inter-vertebral disc space and shape profiles. We present a novel technique to retrieve vertebra pairs that exhibit a specified disc space narrowing (DSN) and inter-vertebral disc shape profile. DSN is characterized using spatial and geometrical features between two adjacent vertebrae. Initial retrieval results are clustered and used to construct a voting committee to retrieve vertebra pairs with the highest DSN similarity. Experimental results show that the proposed algorithm is a promising approach for disc space-based spine X-ray image retrieval. The overall retrieval accuracy validated by a radiologist is 82.25%. C1 [Chang, Yuchou; Lee, Dah-Jye; Christensen, Paul] Brigham Young Univ, Dept Elect & Comp Engn, Provo, UT 84602 USA. [Antani, Sarneer; Long, L. Rodney] Natl Inst Hlth, Natl Lib Med, Bethesda, MD 20894 USA. [Gledhill, Kent] Utah Valley Reg Med Ctr, Provo, UT 84604 USA. RP Chang, YC (reprint author), Brigham Young Univ, Dept Elect & Comp Engn, Provo, UT 84602 USA. EM yuchou.chang@gmail.com; antani@nlm.nih.gov; djlee@ee.byu.edu; kmgtmg@comcast.net; long@nlm.nih.gov; paulchst@gmail.com OI Antani, Sameer/0000-0002-0040-1387 FU National Library of Medicine (NLM) [HHSN276200700335P]; National Institutes of Health (NIH) FX This work research was supported in part by the National Library of Medicine (NLM) under Grant contract HHSN276200700335P and intramural research funds of the Lister Hill National Center for Biomedical Communications, the National Library of Medicine (NLM), and the National Institutes of Health (NIH). NR 19 TC 2 Z9 2 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 2372-9198 BN 978-0-7695-3165-6 J9 COMP MED SY PY 2008 BP 224 EP + DI 10.1109/CBMS.2008.58 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Biomedical; Mathematical & Computational Biology SC Computer Science; Engineering; Mathematical & Computational Biology GA BHZ14 UT WOS:000257577600048 ER PT B AU Brann, TW Frank, AC Yang, J Huang, DW Lempicki, RA Baseler, MW Kottilili, S Lane, HC Imamichi, T AF Brann, T. W. Frank, A. C. Yang, J. Huang, D. W. Lempicki, R. A. Baseler, M. W. Kottilili, S. Lane, H. C. Imamichi, T. BE Hiscott, J TI Interleukin-27 Is a Novel Anti-Viral Cytokine That Inhibits Replication of HIV-1 and HCV SO PROCEEDINGS OF THE 7TH JOINT MEETING OF THE INTERNATIONAL MEETING OF THE INTERNATIONAL CYTOKINE SOCIETY AND THE INTERNATIONAL SOCIETY FOR INTERFERON AND CYTOKINE RESEARCH LA English DT Proceedings Paper CT 7th Joint Conference of the International-Cytokines-Society/International-Society-for-Interferon-and -Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokines Soc, Int Soc Interferon & Cytokin Res ID INTERFERONS; IL-27 AB IL-27 inhibits HIV-1 replication in T cells and macrophages as IFN-alpha does. In this study, the anti-viral effect was compared between the two cytokines. Both cytokines preferentially inhibited HIV-1 replication in macrophages compared with T cells. The gene-expression profiles demonstrated that IL-27 and IFN-alpha induced 28 and 33 IFN-inducible genes in macrophages, respectively, while IL-27 had any impacts on the induction of neither IFN-alpha/beta/gamma proteins from macrophages. These results suggested that IFN-a-like signals but not IFNs appear to be involved in the IL-27-mediated HIV-1 inhibition in macrophages. To expand anti-viral spectrum, impact of IL-27 on HCV replication was assessed. IL-27 suppressed HCV replication in dose dependent manners; therefore, IL-27 is a novel anti-viral cytokine that can inhibit HIV-1 and HCV replication. C1 [Brann, T. W.; Yang, J.; Huang, D. W.; Lempicki, R. A.; Baseler, M. W.; Imamichi, T.] NCI Frederick, Appl & Dev Res Support Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Brann, TW (reprint author), NCI Frederick, Appl & Dev Res Support Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NR 7 TC 0 Z9 0 U1 0 U2 2 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-496-4 PY 2008 BP 15 EP 22 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA BLX48 UT WOS:000271286600003 ER PT B AU Petrenko, L Klaschik, S Shirota, H Klinman, DM AF Petrenko, L. Klaschik, S. Shirota, H. Klinman, D. M. BE Hiscott, J TI Synergistic Up-regulation of Cytokine Genes by CpG Oligonucleotides Plus Poly (I:C) SO PROCEEDINGS OF THE 7TH JOINT MEETING OF THE INTERNATIONAL MEETING OF THE INTERNATIONAL CYTOKINE SOCIETY AND THE INTERNATIONAL SOCIETY FOR INTERFERON AND CYTOKINE RESEARCH LA English DT Proceedings Paper CT 7th Joint Conference of the International-Cytokines-Society/International-Society-for-Interferon-and -Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokines Soc, Int Soc Interferon & Cytokin Res ID DOUBLE-STRANDED-RNA; DENDRITIC CELLS; EXPRESSION; ACTIVATION; INTERLEUKIN-12; MACROPHAGES AB RAW264.7 mouse macrophages were incubated with immunostimulatory CpG ODN and/or poly (I:C), and changes in global mRNA expression levels monitored at 4 and 12 hr using a 36 K mouse microarray. Genes encoding the cytokines IL6, IL1A, IFNA6, IFNB1, and CSF3 were synergistically up-regulated at 4 hours while those encoding IL33, IL6, IL12A, IL12B, IL19, IL10, and IL1F6 were synergistically activated at 12 hours. The interleukins IL33, IL19, IL12A, the chemokine S100A8 and the neurotransmitter NPY genes were not activated individually by either CpG ODN or poly(I:C) but were strongly up-regulated following combined stimulation. These data represent the first evidence of synergistic transcriptional activation of the interleukin genes IL33 and IL19, and help to explain the mechanism by which CpG ODN and poly(I:C) combine to enhance immune responses in vitro and in vivo. C1 [Petrenko, L.; Klaschik, S.; Shirota, H.; Klinman, D. M.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. RP Petrenko, L (reprint author), NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-496-4 PY 2008 BP 65 EP 71 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA BLX48 UT WOS:000271286600012 ER PT B AU Bray, M AF Bray, M. BE Neugebauer, EAM TI Severe Viral Infections SO PROCEEDINGS OF THE INTERNATIONAL SHOCK CONGRESS LA English DT Proceedings Paper CT 6th Congress of the International-Federation-of-Shock-Societies/31st Annual Conference of the Shock-Society/7th Int Conf Complexity in Acute Illness CY JUN 28-JUL 02, 2008 CL Cologne, GERMANY SP Int Federat Shock Soc, Shock Soc ID PATHOGENESIS; INFLUENZA; VIRUS AB Most viruses that circulate among animals fall to cause disease in humans, but a few are fortuitously capable of evading innate immune defenses to produce overwhelming infection. A prime example is Ebola virus, which spreads quickly to monocytes, macrophages and dendritic cells throughout the body, inducing an inflammatory syndrome resembling septic shock. Massive lymphocyte apoptosis contributes to the failure of adaptive immune responses to contain the pathogen. The recently emerged H5N1 avian influenza Virus also causes lethal disease in previously healthy persons. The agent replicates rapidly both within and outside the respiratory tract, inducing acute respiratory distress syndrome and an intense systemic inflammatory response. Management of these diseases should benefit from progress in treating more common types of shock. C1 NIAID, Integrated Res Facil, NIH, Bethesda, MD 20892 USA. RP Bray, M (reprint author), NIAID, Integrated Res Facil, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 2 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-413-1 PY 2008 BP 125 EP 128 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA BIW01 UT WOS:000263264200023 ER PT B AU Deterding, L Bhattacharjee, S Mason, R Tomer, K AF Deterding, L. Bhattacharjee, S. Mason, R. Tomer, K. BE Zhao, B Davies, M Cadeans, E TI Mass Spectrometric Identification of Spin-trapped Protein Free Radicals SO PROCEEDINGS OF THE XIV BIENNIAL MEETING OF THE SOCIETY FOR FREE RADICAL RESEARCH INTERNATIONAL LA English DT Proceedings Paper CT 14th Biennial Meeting of the Society-for-Free-Radical-Research-International CY OCT 18-22, 2008 CL Beijing, PEOPLES R CHINA SP Soc Free Rad Res Int ID HUMAN MYOGLOBIN; ELECTRON-TRANSFER; DAMAGE; H2O2 AB Peptide mapping and MS is powerful technique for detection and determination of protein radicals MS, ESR, and antibody detection are complementary Mass Spectrometry is useful for protein identification and for assignment of sites of spin trapping in protein sequences C1 [Deterding, L.; Tomer, K.] NIEHS, Mass Spectrometry Grp, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Tomer, K (reprint author), NIEHS, Mass Spectrometry Grp, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-498-8 PY 2008 BP 23 EP 29 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BMF36 UT WOS:000272106600004 ER PT B AU Namiki, T Valencia, JC Hearing, VJ AF Namiki, T. Valencia, J. C. Hearing, V. J. BE Jimbow, K TI Approaches to Characterize the Localization and Functions of P and MATP in Melanocytes SO PROCEEDINGS OF THE XXTH INTERNATIONAL PIGMENT CELL CONFERENCE - IPCC AND VTH INTERNATIONAL MELANOMA RESEARCH CONGRESS - IMRC LA English DT Proceedings Paper CT 20th International Pigment Cell Conference/5th International Melanoma Research Congress CY MAY 07-12, 2008 CL Sapporo, JAPAN ID ALBINISM; TYROSINASE AB Oculocutaneous albinism types 2 and 4 are thought to be quite similar in mechanism, but are not well understood at this time. One of the reasons is that efficient antibodies against the P and MATP proteins have not been generated so far. In this study, we attempted to generate antibodies against the P and MATP proteins to detect clear and specific bands corresponding to these proteins. Four antibodies against the P protein and 5 antibodies against the MATP protein were generated by immunization of rabbits with target peptides. Only one antibody for each protein successfully detected a clear and specific band for these proteins. These antibodies will be useful in studies to elucidate the functions of the P and MATP proteins by western blotting and other approaches. C1 [Namiki, T.; Valencia, J. C.; Hearing, V. J.] NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20841 USA. RP Namiki, T (reprint author), NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20841 USA. NR 6 TC 1 Z9 1 U1 1 U2 1 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-474-2 PY 2008 BP 23 EP 27 PG 5 WC Oncology; Dermatology SC Oncology; Dermatology GA BJB33 UT WOS:000264425300006 ER PT B AU Le Pape, E Wakamatsu, K Giubellino, A Valencia, JC Passeron, T Ito, S Wolber, R Hearing, VJ AF Le Pape, E. Wakamatsu, K. Giubellino, A. Valencia, J. C. Passeron, T. Ito, S. Wolber, R. Hearing, V. J. BE Jimbow, K TI Regulation of Melanocyte Fate by Agouti Signal Protein SO PROCEEDINGS OF THE XXTH INTERNATIONAL PIGMENT CELL CONFERENCE - IPCC AND VTH INTERNATIONAL MELANOMA RESEARCH CONGRESS - IMRC LA English DT Proceedings Paper CT 20th International Pigment Cell Conference/5th International Melanoma Research Congress CY MAY 07-12, 2008 CL Sapporo, JAPAN AB The melanocortin 1 receptor (MC1R) is a key regulator of pigmentation that is associated with melanoma risk. Various agonist ligands bind to MC1R and stimulate its activity while agouti signal protein (ASP) is an inverse agonist of MC1R and is responsible for the lighter pigment phenotype both in mice and in humans. In addition, increasing evidence suggests a role for ASP in skin cancer risk. In this study, we demonstrate that ASP is able to inhibit the production of eumelanin in melanocytes within I day of treatment. This dramatic inhibition correlates with the significant reduction of mRNAs encoding various melanogenic factors involved in pigmentation, as revealed by DNA microarrays, which were confirmed at the protein level. Overall, these data emphasize the dedifferentiating role of ASP and provide new targets of MC1R signaling. C1 [Le Pape, E.; Valencia, J. C.; Passeron, T.; Hearing, V. J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Le Pape, E (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-474-2 PY 2008 BP 73 EP 77 PG 5 WC Oncology; Dermatology SC Oncology; Dermatology GA BJB33 UT WOS:000264425300016 ER PT B AU Choi, W Wolber, R Gerwat, W Mann, T Hearing, VJ AF Choi, W. Wolber, R. Gerwat, W. Mann, T. Hearing, V. J. BE Jimbow, K TI Characterization of the Influence of Fibroblasts on Melanocyte Function and Pigmentation SO PROCEEDINGS OF THE XXTH INTERNATIONAL PIGMENT CELL CONFERENCE - IPCC AND VTH INTERNATIONAL MELANOMA RESEARCH CONGRESS - IMRC LA English DT Proceedings Paper CT 20th International Pigment Cell Conference/5th International Melanoma Research Congress CY MAY 07-12, 2008 CL Sapporo, JAPAN ID SKIN PIGMENTATION; DICKKOPF-1; EXPRESSION AB Many paracrine factors produced by keratinocytes and fibroblasts regulate melanocyte function. We hypothesized that fibroblasts might play important roles in regulating constitutive skin color and responses to the environment. Fibroblasts derived from different skin phototypes (I, III and VI) were used to examine their effects on the pigmentation of the MelanoDerm skin model. Further, cDNA microarray analyses revealed that the 3 types of fibroblasts had distinct mRNA expression patterns, and that some secreted factors were expressed differently in fibroblasts from the different skin types that might act as potential melanogenic factors. Overall, this study Suggests that fibroblasts in the dermis play an important role in regulating constitutive skin color via their secreted paracrine factors. C1 [Choi, W.; Hearing, V. J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Choi, W (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-474-2 PY 2008 BP 79 EP 82 PG 4 WC Oncology; Dermatology SC Oncology; Dermatology GA BJB33 UT WOS:000264425300017 ER PT B AU Coelho, SG Zhou, Y Bushar, HF Miller, SA Zmudzka, BZ Hearing, VJ Beer, JZ AF Coelho, S. G. Zhou, Y. Bushar, H. F. Miller, S. A. Zmudzka, B. Z. Hearing, V. J. Beer, J. Z. BE Jimbow, K TI Insights into UV-induced Long-lasting Pigmentation (LLP) in Human Skin SO PROCEEDINGS OF THE XXTH INTERNATIONAL PIGMENT CELL CONFERENCE - IPCC AND VTH INTERNATIONAL MELANOMA RESEARCH CONGRESS - IMRC LA English DT Proceedings Paper CT 20th International Pigment Cell Conference/5th International Melanoma Research Congress CY MAY 07-12, 2008 CL Sapporo, JAPAN ID ULTRAVIOLET-RADIATION; MECHANISMS; ERYTHEMA AB Ultraviolet (UV) exposure stimulates pigmentation of human skin, but little is known about the perseverance of UV-induced tans. UV responses in individuals with different levels of skin pigmentation were initially monitored for 16 clays. Long-lasting pigmentation (LLP) was then evaluated in 60 subjects >= 9 months after UV exposures, and occurred in a considerable segment of these subjects. The physiological role of LLP is under investigation, but it is obvious that predisposition to LLP should be taken into consideration when patients are treated with UV for pigmentary disorders and other skin diseases. The ability to predict LLP may reduce unnecessary radiation exposure from therapeutic and cosmetic devices. Our observations indicate that LLP merits further exploration at the cellular and molecular levels. C1 [Coelho, S. G.; Hearing, V. J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Coelho, SG (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-474-2 PY 2008 BP 137 EP 141 PG 5 WC Oncology; Dermatology SC Oncology; Dermatology GA BJB33 UT WOS:000264425300026 ER PT J AU Maltsev, VA Undrovinas, A AF Maltsev, Victor A. Undrovinas, Albertas TI Late sodium current in failing heart: Friend or foe? SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE late sodium current; heart failure; calcium; action potential; numerical model; sodium-calcium exchanger ID CARDIAC PURKINJE-FIBERS; LATE NA+ CURRENT; HUMAN VENTRICULAR CARDIOMYOCYTES; ACTION-POTENTIAL REPOLARIZATION; HODGKIN-HUXLEY EQUATIONS; SUPPRESSION TRIAL CAST; HUMAN MYOCARDIUM; INTRACELLULAR CALCIUM; SLOW INACTIVATION; MOLECULAR-BASIS AB Most cardiac Na+ channels open transiently upon membrane depolarization and then are quickly inactivated. However, some channels remain active, carrying the so-called persistent or late Na+ current (I-NaL) throughout the action potential (AP) plateau. Experimental data and the results of numerical modeling accumulated over the past decade show the emerging importance of this late current component for the function of both normal and failing myocardium. I-NaL is produced by special gating modes of the cardiac-specific Na+ channel isoform. Heart failure (HF) slows channel gating and increases I-NaL, but HF-specific Na+ channel isoform underlying these changes has not been found. Na+ channels represent a multi-protein complex and its activity is determined not only by the pore-forming alpha subunit but also by its auxiliary beta subunits, cytoskeleton, calmodulin, regulatory kinases and phosphatases, and trafficking proteins. Disruption of the integrity of this protein complex may lead to alterations of I-NaL in pathological conditions. Increased I-NaL and the corresponding Na+ flux in failing myocardium contribute to abnormal repolarization and an increased cell Ca2+ load. Interventions designed to correct I-NaL rescue normal repolarization and improve Ca2+ handling and contractility of the failing cardiomyocytes. This review considers (1) quantitative integration of I-NaL into the established electrophysiological and Ca2+ regulatory mechanisms in normal and failing cardiomyocytes and (2) a new therapeutic strategy utilizing a selective inhibition of I-NaL to target both arrhythmias and impaired contractility in HF. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Undrovinas, Albertas] Henry Ford Hosp, Henry Ford Hlth Syst, Detroit, MI 48202 USA. [Maltsev, Victor A.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Undrovinas, A (reprint author), Henry Ford Hosp, Henry Ford Hlth Syst, Educ & Res Bldg,Room 4015,2799 W Grand Blvd, Detroit, MI 48202 USA. EM aundrov1@hfhs.org FU Intramural NIH HHS; NHLBI NIH HHS [HL-53819, HL074238, R01 HL074328-04] NR 142 TC 50 Z9 50 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD JAN-APR PY 2008 VL 96 IS 1-3 BP 421 EP 451 DI 10.1016/j.pbiomolbio.2007.07.010 PG 31 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 282WN UT WOS:000254598000024 PM 17854868 ER PT J AU Caldwell, HK Lee, HJ Macbeth, AH Young, WS AF Caldwell, Heather K. Lee, Heon-Jin Macbeth, Abbe H. Young, W. Scott, III TI Vasopressin: Behavioral roles of an "original" neuropeptide SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE aggression; stress; circadian; knockout; transgenic; behavior; anxiety; review; paraventricular; supraoptic; suprachiasmatic; Avpr1a; Avpr1b; affiliation; maternal behavior; learning; memory; hippocampus; oxytocin ID RECEPTOR KNOCKOUT MICE; ANXIETY-RELATED BEHAVIOR; VOLES MICROTUS-OCHROGASTER; LATERAL SEPTAL VASOPRESSIN; PASSIVE-AVOIDANCE BEHAVIOR; MESSENGER-RNA EXPRESSION; MALE PRAIRIE VOLES; HOSPITAL CARDIOPULMONARY-RESUSCITATION; ANTERIOR HYPOTHALAMIC VASOPRESSIN; PERVASIVE DEVELOPMENTAL DISORDERS AB Vasopressin (Avp) is mainly synthesized in the magnocellular cells of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN) whose axons project to the posterior pituitary. Avp is then released into the blood stream upon appropriate stimulation (e.g., hemorrhage or dehydration) to act at the kidneys and blood vessels. The brain also contains several populations of smaller, parvocellular neurons whose projections remain within the brain. These populations are located within the PVN, bed nucleus of the stria terminalis (BNST), medial amygdala (MeA) and suprachiasmatic nucleus (SCN). Since the 1950s, research examining the roles of Avp in the brain and periphery has intensified. The development of specific agonists and antagonists for Avp receptors has allowed for a better elucidation of its contributions to physiology and behavior. Anatomical, pharmacological and transgenic, including "knockout," animal studies have implicated Avp in the regulation of various social behaviors across species. Avp plays a prominent role in the regulation of aggression, generally of facilitating or promoting it. Affiliation and certain aspects of pair-bonding are also influenced by Avp. Memory, one of the first brain functions of Avp that was investigated, has been implicated especially strongly in social recognition. The roles of Avp in stress, anxiety, and depressive states are areas of active exploration. In this review, we concentrate on the scientific progress that has been made in understanding the role of Avp in regulating these and other behaviors across species. We also discuss the implications for human behavior. Published by Elsevier Ltd. C1 [Caldwell, Heather K.; Lee, Heon-Jin; Macbeth, Abbe H.; Young, W. Scott, III] NIMH, Sect Neural Gene Express, DHHS, NIH, Bethesda, MD 20892 USA. RP Young, WS (reprint author), 9000 Rockville Pike,Bldg 49,Room 5A60, Bethesda, MD 20892 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009; chen, xuanlan/H-4158-2011; OI Young, W Scott/0000-0001-6614-5112; , Heon-Jin/0000-0002-1911-5014 FU Intramural NIH HHS [Z01 MH002498-18]; NIMH NIH HHS [Z01 MH002498] NR 320 TC 229 Z9 239 U1 7 U2 49 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD JAN PY 2008 VL 84 IS 1 BP 1 EP 24 DI 10.1016/j.pneurobio.2007.10.007 PG 24 WC Neurosciences SC Neurosciences & Neurology GA 259BK UT WOS:000252913900001 PM 18053631 ER PT S AU Pursell, ZF Kunkel, TA AF Pursell, Zachary F. Kunkel, Thomas A. BE Conn, PM TI DNA Polymerase epsilon: A Polymerase of Unusual Size (and Complexity) SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 82 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY LA English DT Review; Book Chapter ID BASE-EXCISION-REPAIR; XENOPUS EGG EXTRACTS; REPLICATION CHECKPOINT RESPONSE; YEAST SACCHAROMYCES-CEREVISIAE; CHROMATIN-REMODELING COMPLEX; STRAND BREAK REPAIR; S-PHASE CHECKPOINT; HISTONE-FOLD PROTEINS; HUMAN MISMATCH REPAIR; CELL NUCLEAR ANTIGEN AB DNA polymerase epsilon (Pol epsilon) is a large, multi-subunit polymerase that is conserved throughout all eukaryotes. In addition to its role as one of the three DNA polymerases responsible for bulk chromosomal replication, Pot epsilon is implicated in a wide variety of important cellular processes, including the repair of damaged DNA, DNA recombination and the regulation of proper cell cycle progression. Additionally, recent work has suggested that Pol epsilon is linked to chromatin remodeling and the regulation of epigenetic inheritance. Though much has been learned in the past two decades about the various functions of Pol epsilon, a great deal remains unknown due in large Part to the complexities of both the various implicated pathways and the Pol epsilon holoenzyme itself. While most of the progress in understanding Pol epsilon has come from work using the human and bakers yeast systems, the Xenopus and fission yeast systems have provided valuable insights. Here we discuss what is currently known about this unique DNA polymerase, from its initial identification through the present. C1 [Pursell, Zachary F.] NIEHS, Dept Hlth & Human Serv, Genet Mol Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Pursell, ZF (reprint author), NIEHS, Dept Hlth & Human Serv, Genet Mol Lab, Natl Inst Hlth, POB 12233, Res Triangle Pk, NC 27709 USA. OI Pursell, Zachary/0000-0001-5871-7192 FU National Institutes of Health; National Institute of Environmental Health Sciences FX The authors thank Drs. Kasia Bebenck and Stephanie Nick McElhinny for thoughtful discussion and comments on the manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 213 TC 39 Z9 39 U1 3 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0079-6603 BN 978-0-12-374549-1 J9 PROG NUCLEIC ACID RE JI Prog. Nucl. Res. Molec. Biol. PY 2008 VL 82 BP 101 EP 145 DI 10.1016/S0079-6603(08)00004-4 PG 45 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIM36 UT WOS:000260775200004 PM 18929140 ER PT B AU Prins, GS Korach, KS AF Prins, Gail S. Korach, Kenneth S. BE Pestell, RG Nevalainen, MT TI Estrogen Action in Normal Prostate Epithelium and in Prostate Cancer SO PROSTATE CANCER: SIGNALING NETWORKS, GENETICS, AND NEW TREATMENT STATEGIES SE Current Clinical Oncology Series LA English DT Article; Book Chapter ID HUMAN ANDROGEN RECEPTOR; BETA ER-BETA; SIGNAL-TRANSDUCTION PATHWAYS; MESSENGER-RIBONUCLEIC-ACID; GUINEA-PIG PROSTATE; GENE-EXPRESSION; RAT PROSTATE; DIFFERENTIAL EXPRESSION; RESPONSIVE GENES; NOBLE RATS C1 [Prins, Gail S.] Univ Illinois, Dept Urol, Chicago, IL 60607 USA. [Korach, Kenneth S.] NIEHS, Environm Dis & Med Program, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Prins, GS (reprint author), Univ Illinois, Dept Urol, Chicago, IL 60607 USA. NR 180 TC 0 Z9 0 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-58829-741-9 J9 CURR CLIN ONCOL PY 2008 BP 181 EP 207 DI 10.1007/978-1-60327-079-3_9 D2 10.1007/978-1-60327-079-3 PG 27 WC Oncology SC Oncology GA BJY12 UT WOS:000267393300009 ER PT J AU Sharma, S Sommers, JA Brosh, RM AF Sharma, Sudha Sommers, Joshua A. Brosh, Robert M., Jr. TI Processing of DNA replication and repair intermediates by the concerted action of RecQ helicases and Rad2 structure-specific nucleases SO PROTEIN AND PEPTIDE LETTERS LA English DT Review DE helicase; nuclease; Werner syndrome; Bloom syndrome; DNA repair; replication ID WERNER-SYNDROME PROTEIN; STIMULATES FLAP ENDONUCLEASE-1; OKAZAKI FRAGMENT MATURATION; ROTHMUND-THOMSON-SYNDROME; SINGLE-STRANDED-DNA; SACCHAROMYCES-CEREVISIAE; BLOOMS-SYNDROME; ESCHERICHIA-COLI; S-PHASE; MISMATCH REPAIR AB Processing of DNA replication and repair intermediates is a critical aspect of genome stability maintenance. The coordinated action of RecQ-like helicases with structure-specific nucleases such as Flap Endonuclease 1 plays an important role in the processing of certain DNA structures associated with the replication fork, DNA repair, or telomeres. We will summarize our current understanding of how and in what context these interactions take place, with a particular emphasis on the mechanisms of RecQ helicases in processing of key DNA replication and repair intermediates by their protein interactions with FEN-1 and related structure-specific nucleases. C1 [Sharma, Sudha; Sommers, Joshua A.; Brosh, Robert M., Jr.] NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, NIH, Lab Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BroshR@grc.nia.nih.gov OI Sharma, Sudha/0000-0003-2765-2482 FU Intramural NIH HHS NR 131 TC 7 Z9 7 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PD JAN PY 2008 VL 15 IS 1 BP 89 EP 102 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 275NV UT WOS:000254079800014 PM 18221018 ER PT S AU Bai, YW AF Bai, Yawen BE Munoz, V TI Hydrogen Exchange Experiments: Detection and Characterization of Protein Folding Intermediates SO PROTEIN FOLDING, MISFOLDING AND AGGREGATION: CLASSICAL THEMES AND NOVEL APPROACHES SE RSC Biomolecular Sciences LA English DT Article; Book Chapter ID MASS-SPECTROMETRY; RIBONUCLEASE-A; CYTOCHROME-C; STRUCTURAL-CHARACTERIZATION; 2-PROCESS MODEL; MOLTEN GLOBULE; PATHWAY; NMR; STATE; APOMYOGLOBIN C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 6114E, Bethesda, MD 20892 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 1757-7152 BN 978-1-84755-828-2; 978-0-85404-257-9 J9 RSC BIOMOL SCI JI RSC Biomol. Sci. PY 2008 BP 70 EP 84 DI 10.1039/9781847558282-00070 D2 10.1039/9781847558282-FP001 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ64 UT WOS:000328508200005 ER PT S AU Dyda, F Hickman, AB AF Dyda, Fred Hickman, Alison Burgess BE Rice, PA Correll, CC TI DNA Transposases SO PROTEIN-NUCLEIC ACID INTERACTIONS: STRUCTURAL BIOLOGY SE RSC Biomolecular Sciences LA English DT Article; Book Chapter ID TRANSPOSITION IN-VITRO; PHAGE MU TRANSPOSASE; SINGLE ACTIVE-SITE; CUT-AND-PASTE; BINDING DOMAIN; V(D)J RECOMBINATION; BACTERIOPHAGE-MU; CRYSTAL-STRUCTURE; SLEEPING-BEAUTY; BACTERIAL TRANSPOSITION C1 [Dyda, Fred; Hickman, Alison Burgess] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dyda, F (reprint author), NIDDKD, Mol Biol Lab, NIH, 5 Ctr Dr,MSC 0560, Bethesda, MD 20892 USA. NR 89 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 1757-7152 BN 978-1-84755-826-8; 978-0-85404-272-2 J9 RSC BIOMOL SCI JI RSC Biomol. Sci. PY 2008 BP 270 EP 302 D2 10.1039/9781847558268-FP001 PG 33 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ09 UT WOS:000328390400012 ER PT J AU Monteiro, RQ Rezaie, AR Bae, JS Calvo, E Andersen, JF Francischetti, IMB AF Monteiro, Robson Q. Rezaie, Alireza R. Bae, Jong-Sup Calvo, Eric Andersen, John F. Francischetti, Ivo M. B. TI Ixolaris binding to factor X reveals a precursor state of factor Xa heparin-binding exosite SO PROTEIN SCIENCE LA English DT Article DE tissue factor; heparin-binding exosite; proexosite; intrinsic tenase; prothrombinase ID FACTOR PATHWAY INHIBITOR; TISSUE FACTOR EXPRESSION; PROTHROMBINASE COMPLEX; PROEXOSITE-I; FACTOR-VIIIA; SUBSTRATE RECOGNITION; CRYSTAL-STRUCTURE; A1 SUBUNIT; COAGULATION; THROMBIN AB Ixolaris is a two-Kunitz tick salivary gland tissue factor pathway inhibitor (TFPI). In contrast to human TFPI, Ixolaris specifically binds to factor Xa (FXa) heparin-binding exosite (HBE). In addition, Ixolaris interacts with zymogen FX. In the present work we characterized the interaction of Ixolaris with human FX quantitatively, and identified a precursor state of the heparin- binding exosite (proexosite, HBPE) as the Ixolaris-binding site on the zymogen. Gel-filtration chromatography demonstrated 1:1 complex formation between fluorescein-labeled Ixolaris and FX. Isothermal titration calorimetry confirmed that the binding of Ixolaris to FX occurs at stoichiometric concentrations in a reaction which is characteristically exothermic, with a favorable enthalpy (Delta H) of -10.78 kcal/mol. ELISA and plasmon resonance experiments also indicate that Ixolaris binds to plasma FX and FXa, or to recombinant Gla domain-containing FX/FXa with comparable affinities (similar to 1nM). Using a series of mutants on the HBPE, we identified the most important amino acids involved in zymogen/Ixolaris interaction-Arg-93 >>> Arg-165 >= Lys-169 > Lys-236 > Arg-125-which was identical to that observed for FXa/ Ixolaris interaction. Remarkably, Ixolaris strongly inhibited FX activation by factor IXa in the presence but not in the absence of factor VIIIa, suggesting a specific interference in the cofactor activity. Further, solid phase assays demonstrated that Ixolaris inhibits FX interaction with immobilized FVIIIa. Altogether, Ixolaris is the first inhibitor characterized to date that specifically binds to FX HBPE. Ixolaris may be a useful tool to study the physiological role of the FX HBPE and to evaluate this domain as a target for anticoagulant drugs. C1 [Calvo, Eric; Andersen, John F.; Francischetti, Ivo M. B.] NIH, Natl Inst All & Infect Dis, Lab Malaria Vector Res, Bethesda, MD 20892 USA. [Monteiro, Robson Q.] Univ Fed Rio de Janeiro, Ctr Ciencias Saude, Inst Bioquim Med, Rio De Janeiro, Brazil. [Rezaie, Alireza R.; Bae, Jong-Sup] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA. RP Francischetti, IMB (reprint author), NIH, Natl Inst All & Infect Dis, Lab Malaria Vector Res, Bldg 10, Bethesda, MD 20892 USA. EM ifrancischetti@niaid.nih.gov RI Monteiro, Robson/B-8007-2014; OI Calvo, Eric/0000-0001-7880-2730 FU Intramural NIH HHS; NHLBI NIH HHS [HL 68571, R01 HL068571] NR 38 TC 27 Z9 27 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 2008 VL 17 IS 1 BP 146 EP 153 DI 10.1110/ps.073016308 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243YZ UT WOS:000251834500016 PM 18042685 ER PT J AU Lobanov, AV Hatfield, DL Gladyshev, VN AF Lobanov, Alexey V. Hatfield, Dolph L. Gladyshev, Vadim N. TI Selenoproteinless animals: Selenophosphate synthetase SPS1 functions in a pathway unrelated to selenocysteine biosynthesis SO PROTEIN SCIENCE LA English DT Article DE selenophosphate synthetase; selenocysteine; selenoproteome; Sec-insertion machinery ID DROSOPHILA-MELANOGASTER; OXIDATIVE STRESS; INSERTION SYSTEM; CELL SYSTEM; IN-SILICO; SEQUENCE; HOMOLOG; GENOME; IDENTIFICATION; GENES AB Proteins containing the 21st amino acid, selenocysteine (Sec), have been described in all three domains of life, but the composition of selenoproteomes in organisms varies significantly. Here, we report that aquatic arthropods possess many selenoproteins also detected in other animals and unicellular eukaryotes, and that most of these proteins were either lost or replaced with cysteine-containing homologs in insects. As a result of this selective selenoproteome reduction, fruit flies and mosquitoes have three known selenoproteins, and the honeybee, Apis mellifera, a single detected candidate selenoprotein. Moreover, we identified the red flour beetle, Tribolium castaneum, and the silkworm, Bombyx mori, as the first animals that lack any Sec-containing proteins. These insects also lost the Sec biosynthesis and insertion machinery, but selenophosphate synthetase 1 (SPS1), an enzyme previously implicated in Sec biosynthesis, is present in all insects, including T. castaneum and B. mori. These data indicate that SPS1 functions in a pathway unrelated to selenoprotein synthesis. Since SPS1 evolved from a protein that utilizes selenium for Sec biosynthesis, an attractive possibility is that SPS1 may define a new pathway of selenium utilization in animals. C1 [Lobanov, Alexey V.; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Hatfield, Dolph L.] NCI, NIH, Lab Canc Prevent, Sect Mol Biol Selenium, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI Gladyshev, Vadim/A-9894-2013 FU Intramural NIH HHS; NIGMS NIH HHS [GM061603, R01 GM061603] NR 27 TC 37 Z9 37 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 2008 VL 17 IS 1 BP 176 EP 182 DI 10.1110/ps.073261508 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243YZ UT WOS:000251834500020 PM 18156471 ER PT J AU Buchete, NV Straub, JE Thirumalai, D AF Buchete, N. -V. Straub, J. E. Thirumalai, D. TI Dissecting contact potentials for proteins: Relative contributions of individual amino acids SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE amino acid ranking; protein folding; contact interactions; amino acid substitution; minimal alphabet for proteins; protein binding; protein design; eigenvalue analysis ID FOLD RECOGNITION; PAIR POTENTIALS; HYDROPHOBICITY PROFILES; STATISTICAL POTENTIALS; PRINCIPAL EIGENVECTOR; DRIVING-FORCE; MATRICES; SIMULATION; STABILITY; SEQUENCES AB Knowledge-based contact potentials are routinely used in fold recognition, binding of peptides to proteins, structure prediction, and coarse-grained models to probe protein folding kinetics. The dominant physical forces embodied in the contact potentials are revealed by eigenvalue analysis of the matrices, whose elements describe the strengths of interaction between amino acid side chains. We propose a general method to rank quantitatively the importance of various inter-residue interactions represented in the currently popular pair contact potentials. Eigenvalue analysis and correlation diagrams are used to rank the inter-residue pair interactions with respect to the magnitude of their relative contributions to the contact potentials. The amino acid ranking is shown to be consistent with a mean field approximation that is used to reconstruct the original contact potentials from the most relevant amino acids for several contact potentials. By providing a general, relative ranking score for amino acids, this method permits a detailed, quantitative comparison of various contact interaction schemes. For most contact potentials, between 7 and 9 amino acids of varying chemical character are needed to accurately reconstruct the full matrix. By correlating the identified important amino acid residues in contact potentials and analysis of about 7800 structural domains in the CATH database we predict that it is important to model accurately interactions between small hydrophobic residues. In addition, only potentials that take interactions involving the protein backbone into account can predict dense packing in protein structures. C1 [Buchete, N. -V.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Straub, J. E.] Boston Univ, Dept Chem, Boston, MA 02215 USA. [Thirumalai, D.] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. RP Buchete, NV (reprint author), NIDDK, Chem Phys Lab, NIH, 9000 Rokville Pike,Bldg 5,Rm 137A, Bethesda, MD 20892 USA. EM buchete@nih.gov RI Buchete, Nicolae-Viorel/C-6200-2015 OI Buchete, Nicolae-Viorel/0000-0001-9861-1157 FU Intramural NIH HHS NR 50 TC 13 Z9 14 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD JAN PY 2008 VL 70 IS 1 BP 119 EP 130 DI 10.1002/prot.21538 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 242BI UT WOS:000251699100012 PM 17640067 ER PT J AU Peisach, E Wang, LB Burroughs, AM Aravind, L Dunaway-Mariano, D Allen, KN AF Peisach, Ezra Wang, Liangbing Burroughs, A. Maxwell Aravind, L. Dunaway-Mariano, Debra Allen, Karen N. TI The X-ray crystallographic structure and activity analysis of a Pseudamonas-specific subfamily of the HAD enzyme superfamily evidences a novel biochemical function SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE haloacid dehalogenase; Pseudomonas; protein : protein interactions; functional genomics; substrate screening; HNOB domain; phosphonatase ID MULTIPLE SEQUENCE ALIGNMENT; PHOSPHONOACETALDEHYDE HYDROLASE; CRYSTAL-STRUCTURE; DEPENDENT PHOSPHOHYDROLASES; DEHALOGENASE SUPERFAMILY; BINDING; PHOSPHATASE; GENOMICS; DIVERSIFICATION; INFORMATION AB The haloacid dehalogenase (HAD) superfamily is a large family of proteins dominated by phosphotransferases. Thirty-three sequence families within the HAD superfamily (HADSF) have been identified to assist in function assignment. One such family includes the enzyme phosphoacetaldehyde hydrolase (phosphonatase). Phosphonatase possesses the conserved Rossmanniod core domain and a Cl-type cap domain. Other members of this family do not possess a cap domain and because the cap domain of phosphonatase plays an important role in active site desolvation and catalysis, the function of the capless family members must be unique. A representative of the capless subfamily, PSPTO_2114, from the plant pathogen Pseudomonas syringae, was targeted for catalytic activity and structure analyses. The X-ray structure of PSPTO_2114 reveals a capless homodimer that conserves some but not all of the inter-subunit contacts contributed by the core domains of the phosphonatase homodimer. The region of the PSPTO_2114 that corresponds to the catalytic scaffold of phosphonatase (and other HAD phosphotransfereases) positions amino acid residues that are ill suited for Mg+2 cofactor binding and mediation of phosphoryl group transfer between donor and acceptor substrates. The absence of phosphotransferase activity in PSPTO_2114 was confirmed by kinetic assays. To explore PSPTO_ 2114 function, the conservation of sequence motifs extending outside of the HADSF catalytic scaffold was examined. The stringently conserved residues among PSPTO_2114 homologs were mapped onto the PSPTO_2114 three-dimensional structure to identify a surface region unique to the family members that do not possess a cap domain. The hypothesis that this region is used in protein-protein recognition is explored to define, for the first time, HADSF proteins which have acquired a function other than that of a catalyst. C1 [Wang, Liangbing; Dunaway-Mariano, Debra] Univ New Mexico, Dept Chem, Albuquerque, NM 87131 USA. [Peisach, Ezra; Allen, Karen N.] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. [Burroughs, A. Maxwell; Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Burroughs, A. Maxwell; Allen, Karen N.] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. RP Dunaway-Mariano, D (reprint author), Univ New Mexico, Dept Chem, Albuquerque, NM 87131 USA. EM dd39@unm.edu; drkallen@bu.edu OI Peisach, Ezra/0000-0002-7905-6327 FU Intramural NIH HHS; NIGMS NIH HHS [GM61099] NR 37 TC 4 Z9 4 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD JAN PY 2008 VL 70 IS 1 BP 197 EP 207 DI 10.1002/prot.21583 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 242BI UT WOS:000251699100019 PM 17654544 ER PT J AU Xiang, Y Goodman, MF Beard, WA Wilson, SH Warshel, A AF Xiang, Yun Goodman, Myron F. Beard, William A. Wilson, Samuel H. Warshel, Arieh TI Exploring the role of large conformational changes in the fidelity of DNA polymerase beta SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE replication fidelity; conformational change; induced fit; enzyme catalysis; free energy landscape. ID MOLECULAR-DYNAMICS SIMULATIONS; FREE-ENERGY SIMULATIONS; STATE KINETIC-ANALYSIS; INDUCED-FIT MECHANISM; REPLICATION FIDELITY; COMPUTER-SIMULATION; ENZYMATIC-REACTIONS; NUCLEOTIDE INCORPORATION; DIHYDROFOLATE-REDUCTASE; CATALYTIC EFFICIENCY AB The relationships between the conformational landscape, nucleotide insertion catalysis and fidelity of DNA polymerase P are explored by means of computational simulations. The simulations indicate that the transition states for incorporation of right (R) and wrong (W) nucleotides reside in substantially different protein conformations. The protein conformational changes that reproduce the experimentally observed fidelity are significantly larger than the small rearrangements that usually accompany motions from the reactant state to the transition state in common enzymatic reactions. Once substrate binding has occurred, different constraints imposed on the transition states for insertion of R and W nucleotides render it highly unlikely that both transition states can occur in the same closed structure, because the predicted fidelity would then be many orders of magnitude too large. Since the conformational changes reduce the transition state energy of W incorporation drastically they decrease fidelity rather than increase it. Overall, a better agreement with experimental data is attained when the R is incorporated through a transition state in a closed conformation and W is incorporated through a transition state in one or perhaps several partially open conformations. The generation of free energy surfaces for R and W also allow us to analyze proposals about the relationship between induced fit and fidelity. C1 [Xiang, Yun; Goodman, Myron F.; Warshel, Arieh] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. [Goodman, Myron F.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. [Beard, William A.; Wilson, Samuel H.] NIEHS, NIH, DHHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Xiang, Y (reprint author), Univ So Calif, Dept Chem, SGM 418,3620 McClintock Ave, Los Angeles, CA 90089 USA. EM yunxiang@usc.edu; warshel@usc.edu FU NCI NIH HHS [U19 CA105010, 5U19CA105010, U19 CA105010-040001]; NIGMS NIH HHS [R01 GM021422, R01 GM021422-23, R01GM21422] NR 81 TC 37 Z9 38 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD JAN PY 2008 VL 70 IS 1 BP 231 EP 247 DI 10.1002/prot.21668 PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 242BI UT WOS:000251699100022 PM 17671961 ER PT S AU Hoorn, EJ Pisitkun, T Yu, MJ Knepper, MA AF Hoorn, Ewout J. Pisitkun, Trairak Yu, Ming-Jiun Knepper, Mark A. BE Thongboonkerd, V TI Proteomic approaches for the study of cell signaling in the renal collecting duct SO PROTEOMICS IN NEPHROLOGY - TOWARDS CLINICAL APPLICATIONS SE Contributions to Nephrology LA English DT Article ID MASS-SPECTROMETRY; AQUAPORIN-2 TRAFFICKING; URINARY BIOMARKERS; LC-MS/MS; VASOPRESSIN; IDENTIFICATION; KIDNEY; PHOSPHORYLATION; EXOSOMES; LABEL AB In the current era of large-scale biology, proteomics has evolved as a powerful, new technique that aims to identify, quantify, and analyze a large number of proteins in a functional context. Therefore, proteomics can be used to study cellular pathways and identify disease biomarkers. In this review, we first outline the principles of two important proteomics techniques that either use difference gel electrophoresis (DIGE) or liquid chromatography (LC) for protein separation, followed by tandem mass spectrometry (MS/MS). The advantages and limitations of each technique are discussed, emphasizing the ability of DIGE to perform quantitative proteomics and the high-throughput and high-sensitivity characteristics of LGMS/MS. We have employed both techniques to unravel the molecular machinery of vasopressin signaling, which governs water homeostasis by recruiting aquaporin-2 (AQP2) water channels after activation of the vasopressin-2 receptor by vasopressin. Several aspects of vasopressin signaling in the inner medullary collecting duct (IMCD) were investigated, including the short- and long-term regulation of AQP2, phosphoproteomics, signaling during vasopressin escape, and the proteomes of AQP2-bearing vesicles and the IMCD plasma membranes. We also emphasize that proteomics of body fluids will be the strategy to identify disease biomarkers, and therefore conclude the review by highlighting the perspectives of biomarker discovery in urinary exosomes. Copyright (c) 2008 S. Karger AG, Basel. C1 [Hoorn, Ewout J.; Pisitkun, Trairak; Yu, Ming-Jiun; Knepper, Mark A.] NHLBI, Lab Kidney & Electrolyte Metab, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Lab Kidney & Electrolyte Metab, NIH, 10 Ctr Dr,Bldg 10,Room 6N260, Bethesda, MD 20892 USA. EM knep@helix.nih.gov OI YU, MING-JIUN/0000-0003-0393-4696 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 32 TC 3 Z9 4 U1 1 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 BN 978-3-8055-8544-6 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2008 VL 160 BP 172 EP 185 DI 10.1159/000125981 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA BHX13 UT WOS:000257140500013 PM 18401169 ER PT J AU Goldstein, MS Lee, JH Ballard-Barbash, R Brown, ER AF Goldstein, Michael S. Lee, Jennifer H. Ballard-Barbash, Rachel Brown, E. Richard TI The use and perceived benefit of complementary and alternative medicine among Californians with cancer SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; complementary and alternative medicine; cancer survivors; coping strategies ID LOCALIZED PROSTATE-CANCER; BREAST-CANCER; THERAPIES; PREVALENCE; TRENDS; WOMEN; MEN AB Population-based data on complementary and alternative medicine (CAM) use among cancer sufferers is lacking. In a telephone survey representative of California households (response rate = 68.9%, N = 1845) those who reported a diagnosis of cancer (excluding non-melanoma skin cancers) were asked about CAM use. CAM use is substantial, although with few exceptions, it is approximately that found among those with non-malignant chronic conditions. Those with cancer are more likely to report praying for their health, using support groups, and taking multiple dietary supplements. They are less apt to use CAM providers or special diets. Socio-demographic factors associated with CAM use vary by specific CAM modality. Site of the cancer was not associated with any particular CAM modality. The use of CAM therapies specifically promoted as cancer therapies was not common, especially among those diagnosed recently. The use of CAM providers and mind-body techniques specifically for the purpose of treating cancer is unusual (<10%), while special diets are more frequently employed for the purpose of treatment and/or prevention of the cancer itself. A clear majority of those who do use CAM for treating cancer report at least some benefit from the treatment, and are likely to inform their physicians of such use. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Goldstein, Michael S.; Brown, E. Richard] Univ Calif Los Angeles, Ctr Hlth Policy Res, Los Angeles, CA 90024 USA. [Ballard-Barbash, Rachel] NCI, NIH, Bethesda, MD 20892 USA. RP Goldstein, MS (reprint author), Univ Calif Los Angeles, Ctr Hlth Policy Res, Los Angeles, CA 90024 USA. EM msgold@ucla.edu RI Lee, Jennifer/C-2698-2008 FU NCI NIH HHS [N02-PC-95057] NR 25 TC 24 Z9 24 U1 4 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2008 VL 17 IS 1 BP 19 EP 25 DI 10.1002/pon.1193 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 253RT UT WOS:000252536000003 PM 17410526 ER PT J AU Button, TMM Lau, JYF Maughan, B Eley, TC AF Button, T. M. M. Lau, J. Y. F. Maughan, B. Eley, T. C. TI Parental punitive discipline, negative life events and gene-environment interplay in the development of externalizing behavior SO PSYCHOLOGICAL MEDICINE LA English DT Article DE externalizing behavior; gene-environment correlation; gene-environment interaction; negative life events; punitive discipline ID ANTISOCIAL-BEHAVIOR; EARLY ADOLESCENCE; HARSH DISCIPLINE; CHILDHOOD; GENOTYPE; TWIN; PERSONALITY; CHILDREN; PSYCHOPATHOLOGY; PREDICTORS AB Background. To investigate the extent to which three putative 'environmental' risk factors, maternal punitive discipline (MPD), paternal punitive discipline (PPD) and negative life events (NLEs), share genetic influences with, and moderate the heritability of, externalizing behavior. Methods. The sample consisted of 2647 participants, aged 12-19 years, from the G1219 and G1219Twins longitudinal studies. Externalizing behavior was measured using the Youth Self-Report, MPD, PPD and exposure to NLEs were assessed using the Negative Sanctions Scale and the Life Event Scale for Adolescents respectively. Results. Genetic influences overlapped for externalizing behavior and each 'environmental' risk, indicating gene-environment correlation. When controlling for the gene-environment correlation, genetic variance decreased, and both shared and non-shared environmental influences increased, as a function of MPD. Genetic variance increased as a function of PPD, and for NLEs the only interaction effect was on the level of non-shared environment influence unique to externalizing behavior. Conclusions. The magnitude of the influence of genetic risk on externalizing behavior is contextually dependent, even after controlling for gene-environment correlation. C1 [Button, T. M. M.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Lau, J. Y. F.] NIMH, NIH, Bethesda, MD 20892 USA. [Lau, J. Y. F.; Maughan, B.; Eley, T. C.] Kings Coll London, Inst Psychiat, Genet & Dev Psychiat Ctr, MRC Social, London WC2R 2LS, England. RP Button, TMM (reprint author), Univ Colorado, Inst Behav Genet, 447 UCB, Boulder, CO 80309 USA. EM tanya.button@colorado.edu RI Eley, Thalia/D-4811-2011 FU Medical Research Council [G0500953, G120/635, G9901475]; NIAAA NIH HHS [T32 AA007464, T32 AA007464-34]; NIDA NIH HHS [DA-011015, P60 DA011015, P60 DA011015-10] NR 40 TC 36 Z9 36 U1 2 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2008 VL 38 IS 1 BP 29 EP 39 DI 10.1017/S0033291707001328 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 269RF UT WOS:000253666100003 PM 17803832 ER PT J AU Blair, KS Finger, E Marsh, AA Morton, J Mondillo, K Buzas, B Goldman, D Drevets, WC Blair, RJR AF Blair, K. S. Finger, E. Marsh, A. A. Morton, J. Mondillo, K. Buzas, B. Goldman, D. Drevets, W. C. Blair, R. J. R. TI The role of 5-HTTLPR in choosing the lesser of two evils, the better of two goods: examining the impact of 5-HTTLPR genotype and tryptophan depletion in object choice SO PSYCHOPHARMACOLOGY LA English DT Article DE decision; tryptophan depletion; 5-HTTLPR genotype; reward; punishment ID PREFRONTAL SEROTONIN DEPLETION; HEALTHY-VOLUNTEERS; GENETIC-VARIATION; DECISION-MAKING; TRANSPORTER POLYMORPHISM; COGNITIVE INFLEXIBILITY; PROMOTER REGION; HUMAN AMYGDALA; RECOGNITION; DEPRESSION AB Rationale The serotonin (5-HT) system is considered important for decision-making. However, its role in reward- and punishment-based processing has not yet been clearly determined. Objectives The present study examines the effect of 5-HTTLPR genotype and tryptophan depletion on reward- and punishment-related processing, using a task that considers decision-making in situations of subtlety of choice. Thus, it considers that response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or creme caramel cheesecake from a menu) or undesirable. It also considers that response choice is easier when the reinforcements associated with the options are far apart, rather than close, in value. Materials and methods Healthy volunteers underwent acute tryptophan depletion (ATD) or control procedures and genotyping of the 5-HTTLPR for long and short allele variants. We then examined the effects and interactions of ATD and the serotonin promoter polymorphism genotype on two aspects of decision-making: (a) decision form, choosing between two objects to gain the greater reward or lesser punishment and (b) between-object reinforcement distance, the difference in reinforcements associated with two options. Results ATD and LL homozygosity had comparable interactions with decision form and between-object reinforcement distance. Specifically, both modulated the effect of between-object reinforcement distance when deciding between objects both associated with punishment. Moreover, ATD and genotype interacted with ATD disproportionately affecting the performance of the LL homozygous group. Conclusions These results suggest that serotonin is particularly associated with punishment, rather than reward-related processing, and that individual sensitivity to punishment-related information and tryptophan depletion varies with genotype. C1 [Blair, K. S.; Finger, E.; Marsh, A. A.; Mondillo, K.; Buzas, B.; Drevets, W. C.; Blair, R. J. R.] NIH, NIMH, Mood & Anxiety Program, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Morton, J.] UCL, Inst Cognit Neurosci, London, England. [Goldman, D.] NIH, Natl Inst Alcohol Abuse & Alcoholism, Neurogenet Lab, Bethesda, MD 20892 USA. RP Blair, KS (reprint author), NIH, NIMH, Mood & Anxiety Program, Dept Hlth & Human Serv, 15K N Dr,Room 300A,MSC 2670, Bethesda, MD 20892 USA. EM peschark@mail.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU Intramural NIH HHS NR 35 TC 19 Z9 20 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2008 VL 196 IS 1 BP 29 EP 38 DI 10.1007/s00213-007-0920-y PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 250KN UT WOS:000252298900003 PM 17940752 ER PT J AU Walsh, SL Chausmer, AE Strain, EC Bigelow, GE AF Walsh, S. L. Chausmer, A. E. Strain, E. C. Bigelow, G. E. TI Evaluation of the mu and kappa opioid actions of butorphanol in humans through differential naltrexone blockade SO PSYCHOPHARMACOLOGY LA English DT Article DE opioid; opioid receptor; opiate; agonist; human; antagonist; drug abuse ID AGONIST-ANTAGONIST OPIOIDS; RHESUS-MONKEYS; RECEPTOR; MORPHINE; HYDROMORPHONE; DISCRIMINATION; PHARMACOLOGY; NALBUPHINE; VOLUNTEERS; MECHANISM AB Rationale Butorphanol exerts activity at mu, kappa, and delta opiate receptors in rats and monkeys but produces predominant mu-like effects in humans. Objectives The aim of this study was to determine if the kappa receptor-mediated actions of butorphanol could be unmasked or enhanced by giving it in combination with naltrexone, an opioid antagonist with higher affinity for mu vs kappa receptors. Materials and methods Ten healthy adult inpatient volunteers (eight men, two women), with opioid abuse histories, completed this double-blind, randomized, placebo-controlled study. Naltrexone (0, 1, 3, 10, or 30 mg, p.o.) was administered 1 h before butorphanol (0, 6, or 12 mg/70 kg, i.m.) during 15 test sessions. An array of physiological (e.g., vital signs, urine output, and subject- and observer-rated) measures was collected before and for 4 h after drug administration. Results Naltrexone alone produced no direct effects. Butorphanol alone produced typical mu-, but not kappa-, related physiological effects (e.g., miosis, respiratory depression) and produced mood and drug effects considered typical of both mu (e.g., "liking," "good drug effects") and kappa agonists (e.g., increases in perceptual disturbances). Naltrexone pretreatment led to significant butorphanol-induced diuresis (i.e., increased urine output and decreased urine osmolality). Naltrexone generally produced a dose-dependent blockade of subjective responses. Conclusion These data suggest that naltrexone antagonism unveiled the kappaergic activity of butorphanol as measured by diuresis, while subjective responses generally attributed to mu vs kappa receptors were not dissociable. Moreover, these data demonstrate that butorphanol exerts physiologically relevant kappa agonist activity at these supraanalgesic doses in humans. C1 [Chausmer, A. E.] Natl Inst Drug Abuse, Behav & Cognit Sci Res Branch, Rockville, MD USA. [Strain, E. C.; Bigelow, G. E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. RP Walsh, SL (reprint author), Univ Kentucky, Coll Med, Dept Behav Sci, Lexington, KY 40536 USA. EM sharon.walsh@uky.edu FU NIDA NIH HHS [K02DA00332, R01 DA016718-03, R01DA016718, R01 DA010753-07, K02 DA000332-05, R01 DA016718, R01 DA010753, R01DA100753, K02 DA000332] NR 45 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2008 VL 196 IS 1 BP 143 EP 155 DI 10.1007/s00213-007-0948-z PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 250KN UT WOS:000252298900014 PM 17909753 ER PT J AU Karlsson, RM Choe, JS Cameron, HA Thorsell, A Crawley, JN Holmes, A Heilig, M AF Karlsson, Rose-Marie Choe, Jessica S. Cameron, Heather A. Thorsell, Annika Crawley, Jacqueline N. Holmes, Andrew Heilig, Markus TI The neuropeptide YY1 receptor subtype is necessary for the anxiolytic-like effects of neuropeptide Y, but not the antidepressant-like effects of fluoxetine, in mice SO PSYCHOPHARMACOLOGY LA English DT Article DE neuropeptide Y; Y1; receptor; knockout; mouse; fear; anxiety; depression; neurogenesis ID CENTRAL-NERVOUS-SYSTEM; ELEVATED PLUS-MAZE; DENTATE GYRUS; HIPPOCAMPAL NEUROGENESIS; KNOCKOUT MICE; ANIMAL-MODELS; C57BL/6J MICE; FOOD-INTAKE; SHORT-TERM; ANXIETY AB Rationale Neuropeptide Y (NPY) is implicated in the pathophysiology of affective illness. Multiple receptor subtypes (Y1R, Y2R, and Y5R) have been suggested to contribute to NPY's effects on rodent anxiety and depression-related behaviors. Objectives To further elucidate the role of Y1R in (1) NPY's anxiolytic-like effects and (2) fluoxetine's antidepressant-like and neurogenesis-inducing effects. Methods Mice lacking Y1R were assessed for spontaneous anxiety-like behavior (open field, elevated plus-maze, and light/dark exploration test) and Pavlovian fear conditioning, and for the anxiolytic-like effects of intracerebroventricularly (icv)-administrated NPY (elevated plus-maze). Next, Y1R -/- were assessed for the antidepressant-like effects of acute fluoxetine in the forced swim test and chronic fluoxetine in the novelty-induced hypophagia test, as well as for chronic fluoxetine-induced hippocampal neurogenesis. Results Y1R -/- exhibited largely normal baseline behavior as compared to +/+ littermate controls. Intraventricular administration of NPY in Y1R -/- mice failed to produce the normal anxiolytic-like effect in the elevated plus-maze test seen in +/+ mice. Y1R mutant mice showed higher immobility in the forced swim test and longer latencies in the novelty-induced hypophagia test. In addition, Y1R -/- mice responded normally to the acute and chronic effects of fluoxetine treatment in the forced swim test and the novelty-induced hypophagia test, respectively, as well as increased neuronal precursor cell proliferation in the hippocampus. Conclusions These data demonstrate that Y1R is necessary for the anxiolytic-like effects of icv NPY, but not for the antidepressant-like or neurogenesis-inducing effects of fluoxetine. The present study supports targeting Y1R as a novel therapeutic target for anxiety disorders. C1 NIAAA, NIH, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. Karolinska Inst, Dept Clin Neurosci, Sect Psychiat, Stockholm, Sweden. NIAAA, NIH, Lab Integrat Neurosci, Sect Behavioral Sci & Genet, Bethesda, MD USA. NIMH, NIH, Unit Neuroplast Mood & Anxiety Disorder Program, Bethesda, MD USA. NIMH, NIH, Lab Behav Neurosci, Bethesda, MD USA. RP Karlsson, RM (reprint author), NIAAA, NIH, Lab Clin & Translat Studies, 10 Ctr Dr,1-5330, Bethesda, MD 20892 USA. EM karlssonr@mail.nih.gov RI Cameron, Heather/E-6221-2011; OI Cameron, Heather/0000-0002-3245-5777; Heilig, Markus/0000-0003-2706-2482; Thorsell, Annika/0000-0003-3535-3845 FU NIH HHS [NH002784, NH02177] NR 64 TC 60 Z9 65 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2008 VL 195 IS 4 BP 547 EP 557 DI 10.1007/s00213-007-0945-2 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 234GD UT WOS:000251147800011 PM 17891380 ER PT J AU Trivedi, MH Kocsis, JH Thase, ME Morris, DW Wisniewski, SR Leon, AC Gelenberg, AJ Klein, DN Niederehe, G Schatzberg, AF Ninan, PT Keller, MB AF Trivedi, Madhukar H. Kocsis, James H. Thase, Michael E. Morris, David W. Wisniewski, Stephen R. Leon, Andrew C. Gelenberg, Alan J. Klein, Daniel N. Niederehe, George Schatzberg, Alan F. Ninan, Philip T. Keller, Martin B. TI REVAMP - Research Evaluating the Value of Augmenting Medication with Psychotherapy: Rationale and Design SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article DE antidepressant; algorithm; pharmacotherapy; psychotherapy; augmentation; remission; response; measurement-based care; personalized care AB This report presents the rationale, design, and baseline sample characteristics for the REVAMP study. This project is a multisite clinical trial designed to evaluate the efficacy of augmenting state-of-the-art pharmacotherapy with psychotherapy in chronically depressed patients who fail to respond or respond incompletely to an initial trial of antidepressant medication. Background: Chronic forms of major depression disorder (cMDD) are longitudinally continuous forms of major depressive disorder (MDD), and may account for a significant portion of the societal burden of disease associated with MDD. Antidepressant medications and depression-focused psychotherapies have been shown to be effective for cMDD, though the majority fail to achieve remission following an acute course of treatment. There is a pressing need to evaluate whether the outcomes obtained from a well implemented medication algorithm combined with depression-focused psychotherapy can significantly enhance outcomes for cMDD. Rationale: Although there is evidence for the effectiveness of depression-focused psychotherapy for the treatment of cMDD, this is the first prospective, randomized, controlled trial investigating psychotherapy as an augmentation strategy for patients with cMDD incompletely responsive to a trial of antidepressant medication. Specific Aims: The REVAMP study has three specific aims: first, to compare the efficacy of adding psychotherapy to a medication change versus changing medication alone in chronic depressives with partial response or nonresponse to an initial trial of antidepressant medication; second, to test efficacy of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) as an augmentation strategy by comparing it to Supportive Psychotherapy (SP); and third, to test a hypothesized mechanism of therapeutic action of CBASP by examining whether patients receiving CBASP exhibit significantly greater improvements in social problem solving than patients receiving adjunctive SP or continued medication alone. As a subsidiary aim, the study also compares the effects of the three randomized treatments on psychosocial outcomes. Design: The study involves two 12-week phases. During Phase 1, patients with cMDD receive antidepressant monotherapy selected according to an algorithm that takes into account their prior treatment history. Their pattern of response is evaluated, those with no response at 8 weeks or less than a full response at 12 weeks advance to Phase 2. At the beginning of Phase 2, patients who did not respond to the initial antidepressant monotherapy during Phase 1 are switched to the next medication in the pharmacotherapy algorithm and randomly assigned in a 2:2: ratio to one of three treatment cells: 16 sessions of either CBASP (40% of randomizations) or SP (40%) added to pharmacotherapy, or medication alone (20%) with no added psychotherapy. Similarly, patients achieving a partial response during Phase 1 have their initial medication augmented with a second antidepressant agent during Phase 2 and are randomly assigned to either CBASP, SP, or medication alone. Patients who achieve remission during Phase 1 are not randomized to Phase 2, but rather are monitored monthly for an additional 12 weeks. Comment: Recent sequential treatment studies have provided state-of-the-art knowledge about the need for multiple steps in order to achieve remission. The current study, therefore, provides an important next step in understanding the role of depression-focused psychotherapy in a treatment algorithm so essential in the management of difficul-to-treat depression such as chronic forms of major depression. Psychopharmacology Bulletin. 2008; 41(4): 5-33. C1 [Trivedi, Madhukar H.; Morris, David W.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Kocsis, James H.; Leon, Andrew C.] Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY USA. [Thase, Michael E.] Univ Penn Sch Med, Philadelphia, PA USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Dept Psychiat, Pittsburgh, PA USA. [Gelenberg, Alan J.] Univ Arizona, Dept Psychiat, Tucson, AZ USA. [Klein, Daniel N.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Niederehe, George] NIMH, Geriatr Res Branch, Bethesda, MD 20892 USA. [Schatzberg, Alan F.] Stanford Univ Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Ninan, Philip T.] Emory Univ Sch Med, Dept Psychiat, Mood & Anxiety Disorders Program, Collegeville, PA USA. [Keller, Martin B.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP Trivedi, MH (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM madhukar.trivedi@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860 FU Cornell University [UO1 MH62475]; University of Pittsburgh [UO1 MH61587]; University of Stony Brook [UO1 MH62546]; University of Texas Southwestern Medical Center [UO1 MH61562]; Emory University School of Medicine [UO1 MH63481]; University of Arizona [UO1 MH62465]; Brown Medical School [UO1 MH61590]; Stanford University [UO1 MH61504]; Agency for Healthcare Research and Quality; Corcept Therapeutics, Inc.; Cyberonics, Inc.; Merck; National Alliance for Research MedAvante, Inc.; Neuronetics, Inc.; Novartis; Organon Inc.; Sepracor, Inc.; Shire US, Inc.; Transcept; Wyeth Pharmaceuticals; AstraZeneca; Bristol-Myers Squibb; Eli Lilly Co.; GlaxoSmithKline; Sepracor; American Psychiatric Publishing, Inc; Guilford Publications and Herald House FX Cornell University (UO1 MH62475): James H. Kocsis, M.D.; John C. Markowitz, M.D.; Andrew C. Leon, Ph.D.; Richard A. Friedman, M.D.; University of Pittsburgh (UO1 MH61587): Michael E. Thase, M.D.; Edward S. Friedman, M.D.; Robert H. Howland, M.D.; Stephen R. Wisniewski, Ph.D.; Jennifer Barkin, M.S.; University of Stony Brook (UO1 MH62546): Daniel N. Klein, Ph.D.; Dina Vivian, Ph.D.; Frank Dowling, M. D.; Thomas D'Zurilla, Ph.D.; University of Texas Southwestern Medical Center (UO1 MH61562): Madhukar H. Trivedi, M. D.; Prabha Sunderajan, M.D.; David W. Morris, Ph.D.; Beverly Kleiber, Ph.D.; Emory University School of Medicine (UO1 MH63481): Barbara O. Rothbaum, Ph.D.; Broadie Dunlop, M.D.; Philip T. Ninan, M.D.; Steven J. Garlow, M.D., Ph.D.; University of Arizona (UO1 MH62465): Alan J. Gelenberg, M.D.; John Misiazek, M.D.; Brown Medical School (UO1 MH61590): Martin B. Keller, M. D.; Ivan Miller, M.D.; Gabor Keitner, M. D.; Susan Raffa, Ph.D.; Stanford University (UO1 MH61504): Alan Schatzberg, M.D.; Bruce Arnow, Ph.D.; Rachel Manber, Ph.D.; Brent Solvason, M.D., Ph.D.; NIMH collaborators: George Niederehe, Ph.D; Louise Ritz, M.B.A.; Elizabeth Zachariah, M.S.; Madhukar H. Trivedi, M. D. has been a consultant or served on speakers bureaus for Abbott Laboratories, Inc.; Abdi Brahim; Akzo (Organon Pharmaceuticals Inc.); AstraZeneca; Bristol-Myers Squibb Company; Cephalon, Inc.; Fabre-Kramer Pharmaceuticals, Inc. Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products, LP; Johnson & Johnson PRD; Eli Lilly & Company; Meade Johnson; Neuronetics; Parke-Davis Pharmaceuticals, Inc.; Pfizer, Inc.; Sepracor; VantagePoint; and Wyeth-Ayerst Laboratories. He has received research support from the Agency for Healthcare Research and Quality; Corcept Therapeutics, Inc.; Cyberonics, Inc.; Merck; National Alliance for Research MedAvante, Inc., Neuronetics, Inc., Novartis, Organon Inc., Sepracor, Inc., Shire US, Inc., Transcept, and Wyeth Pharmaceuticals. Dr Thase has received honoraria for talks sponsored by: AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., and Wyeth Pharmaceuticals. Dr Thase has received grants from Eli Lilly & Co., GlaxoSmithKline, and Sepracor. He has equity holdings in MedAvante, Inc and receives income from royalties from American Psychiatric Publishing, Inc., Guilford Publications and Herald House. NR 105 TC 4 Z9 4 U1 1 U2 5 PU MEDWORKS MEDIA GLOBAL, LLC PI HERMOS BEACH PA 670 FIFTH STREET, STE A, HERMOS BEACH, CA 90254 USA SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 2008 VL 41 IS 4 BP 5 EP 33 PG 29 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA V15HJ UT WOS:000207792800001 PM 19015627 ER PT J AU Dunning, JP Hajcak, G Parvaz, MA Maloney, T Alia-Klein, N Woicik, PA Telaug, F Wang, GJ Volkow, ND Goldstein, RZ AF Dunning, Jonathan P. Hajcak, Greg Parvaz, Muhammad A. Maloney, Thomas Alia-Klein, Nelly Woicik, Patricia A. Telaug, Frank Wang, Gelle-Jack Volkow, Nora D. Goldstein, Rita Z. TI Differential electrocortical response to drug stimuli between cocaine addicts and healthy controls SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 01-05, 2008 CL Austin, TX SP Soc Psychophysiol Res C1 [Dunning, Jonathan P.; Hajcak, Greg] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Parvaz, Muhammad A.; Maloney, Thomas; Alia-Klein, Nelly; Woicik, Patricia A.; Telaug, Frank; Wang, Gelle-Jack; Goldstein, Rita Z.] Brookhaven Natl Lab, Upton, NY 11973 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2008 VL 45 SU 1 BP S53 EP S53 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 347LX UT WOS:000259144200225 ER PT J AU Ernst, M Maheu, FS Pine, DS Dozier, M AF Ernst, Monique Maheu, Francoise S. Pine, Daniel S. Dozier, Mary TI Early adverse care-giving may damage the functional integrity of the medial temporal cortex as evidenced by an fMRI study of adopted adolescents with history of early maltreatment SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 48th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 01-05, 2008 CL Austin, TX SP Soc Psychophysiol Res C1 [Ernst, Monique; Maheu, Francoise S.; Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA. [Dozier, Mary] Univ Delaware, Newark, DE 19716 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2008 VL 45 SU 1 BP S4 EP S5 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 347LX UT WOS:000259144200017 ER PT J AU Vaccarino, V McClure, C Johnson, BD Sheps, DS Bittner, V Rutledge, T Shaw, LJ Sopko, G Olson, MB Krantz, DS Parashar, S Marroqui, OC Merz, CNB AF Vaccarino, Viola McClure, Candace Johnson, B. Delia Sheps, David S. Bittner, Vera Rutledge, Thomas Shaw, Leslee J. Sopko, George Olson, Marian B. Krantz, David S. Parashar, Susmita Marroqui, Oscar C. Merz, C. Noel Bairey TI Depression, the metabolic syndrome and cardiovascular risk SO PSYCHOSOMATIC MEDICINE LA English DT Article DE depression; cardiovascular disease; women; metabolic syndrome; obesity ID CORONARY-ARTERY-DISEASE; SYNDROME EVALUATION WISE; INSULIN-RESISTANCE; HEART-DISEASE; MYOCARDIAL-INFARCTION; MAJOR DEPRESSION; YOUNG-ADULTS; WOMEN; MORTALITY; SYMPTOMS AB Background: The relationship between depression and the metabolic syndrome is unclear, and whether metabolic syndrome explains the association between depression and cardiovascular disease (CVD) risk is unknown. Methods: We studied 652 women who received coronary angiography as part of the Women's Ischemia Syndrome Evaluation (WISE) study and completed the Beck Depression Inventory (BDI). Women who had both elevated depressive symptoms (BD1 >= 10) and a previous diagnosis of depression were considered at highest risk, whereas those with one of the two conditions represented an intermediate group. The metabolic syndrome was defined according to the ATP-III criteria. The main outcome was incidence of adverse CVD events (hospitalizations for myocardial infarction, stroke, congestive heart failure, and CVD-related mortality) over a median follow-up of 5.9 years. Results: After adjusting for demographic factors, lifestyle and functional status, both depression categories were associated with about 60% increased odds for metabolic syndrome compared with no depression (p = .03). The number of metabolic syndrome risk factors increased gradually across the three depression categories (p = .003). During follow-up, 104 women (15.9%) experienced CVD events. In multivariable analysis, women with both elevated symptoms and a previous diagnosis of depression had 2.6 times higher risk of CVD. When metabolic syndrome was added to the model, the risk associated with depression only decreased by 7%, and both depression and metabolic syndrome remained significant predictors of CVD. Conclusions: In women with suspected coronary artery disease, the metabolic syndrome is independently associated with depression but explains only a small portion of the association between depression and incident CVD. C1 [Vaccarino, Viola; Shaw, Leslee J.] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA 30306 USA. [Parashar, Susmita] Emory Univ, Sch Med, Dept Med, Div Gen Med, Atlanta, GA USA. [McClure, Candace; Johnson, B. Delia; Olson, Marian B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Marroqui, Oscar C.] Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA USA. [Sheps, David S.] Univ Florida, Dept Med, Div Cardiovasc Med, Gainesville, FL USA. [Bittner, Vera] Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Rutledge, Thomas] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA. [Krantz, David S.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Merz, C. Noel Bairey] Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA. RP Vaccarino, V (reprint author), Emory Univ, Sch Med, Dept Med, Div Cardiol, 1256 Briarcliff Rd NE,Suite-1 N, Atlanta, GA 30306 USA. EM viola.vaccarino@emory.edu RI Krantz, David/L-5364-2015; Marroquin, Oscar/F-2214-2015; OI Krantz, David/0000-0002-1671-1355; Marroquin, Oscar/0000-0002-0909-0319; Bittner, Vera/0000-0001-9456-850X FU NCRR NIH HHS [M01-RR00425]; NHLBI NIH HHS [N01-HV-68162, K24HL077506, N01-HV-68161, N01-HV-68163, N01-HV-68164, R01-HL68630]; NIA NIH HHS [R01 AG026255] NR 40 TC 82 Z9 85 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN PY 2008 VL 70 IS 1 BP 40 EP 48 DI 10.1097/PSY.0b013e31815c1b85 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 253GM UT WOS:000252506700007 PM 18158378 ER PT J AU Cowan, MJ Freedland, KE Burg, MM Saab, PG Youngblood, ME Cornel, CE Powell, LH Czajkowski, SM AF Cowan, Marie J. Freedland, Kenneth E. Burg, Matthew M. Saab, Patrice G. Youngblood, Marston E. Cornel, Carol E. Powell, Lynda H. Czajkowski, Susan M. TI Predictors of treatment response for depression and inadequate social support - The ENRICHD Randomized clinical trial SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE depression, outcome; low perceived social support; cognitive behavioral therapy; psychosocial intervention ID COGNITIVE-BEHAVIORAL-THERAPY; HEART-DISEASE ENRICHD; PSYCHODYNAMIC-INTERPERSONAL PSYCHOTHERAPY; ENHANCING RECOVERY; MYOCARDIAL-INFARCTION; HOMEWORK COMPLIANCE; TREATMENT DURATION; MORTALITY; MODERATE; DISORDERS AB Objective: To determine whether the 'dose' of treatment exposure, delivery of specific components of cognitive behavior therapy (CBT), patient adherence and/or use of antidepressants predict favorable depression and social support outcomes after 6 months of cognitive behavioral treatment. Methods: Secondary analyses of the intervention arm of the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial involving persons with acute myocardial infarction (MI): n = 641 for the depression outcomes and n = 523 for the social support outcomes. The outcome measures were, for depression: the Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAM-D); for social support: the ENRICHD Social Support Instrument (ESSI) and Perceived Social Support Scale (PSSS). Results: Better depression outcomes (measured by the BDI) were receiving a high number of depression- specific intervention components, p < 0.01, and completing a high proportion of homework assignments, p < 0.02. Better depression outcomes (measured by the HAM-D) were receiving a high number of the social communication and assertiveness components of the intervention, p < 0.01, and completing a high proportion of homework assignments, p < 0.01. Better social support outcomes (measured by the ESSI and PSSS) were predicted by membership in a racial or ethnic minority group, p < 0.02 and p < 0.01, respectively; and by completing a higher number of homework assignments, p < 0.01 and p < 0.05, respectively. Delivery of the social communication and assertiveness components of the intervention was an independent predictor of a worse social support outcome, p < 0.01 ( measured by the PSSS). Conclusions: The standard components of CBT for depression are useful in treating comorbid depression in post-MI patients. Working on communication skills may help to improve depression but not necessarily social support outcomes in this patient population, while adherence to cognitive- behavioral homework assignments is important for both outcomes. Other components of the ENRICHD intervention that were designed to improve social support had no discernible effects on outcomes. Intervention refinements may be needed in order to achieve better results in future post- MI clinical trials. A greater emphasis on CBT homework adherence could improve both depression and social support outcomes. Copyright (c) 2008 S. Karger AG, Basel. C1 [Cowan, Marie J.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. [Freedland, Kenneth E.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Burg, Matthew M.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Burg, Matthew M.] Columbia Univ, Sch Med, New York, NY USA. [Saab, Patrice G.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Youngblood, Marston E.] Univ N Carolina, Dept Biostat, CSCC, Chapel Hill, NC USA. [Cornel, Carol E.] Univ Arkansas Med Sci, Coll Publ Hlth, Dept Hlth Behav & Hlth Educ, Little Rock, AR 72205 USA. [Powell, Lynda H.] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. [Czajkowski, Susan M.] NHLBI, Bethesda, MD 20892 USA. RP Cowan, MJ (reprint author), Univ Calif Los Angeles, Sch Nursing, POB 951702, Los Angeles, CA 90095 USA. EM mcowan@sonnet.ucla.edu FU NHLBI NIH HHS [N01-HC-55140, N01-HC-55141, N01-HC-55142, N01-HC-55143, N01-HC-55144, N01-HC-55145, N01-HC-55146, N01-HC-55147, N01-HC-55148] NR 37 TC 27 Z9 27 U1 3 U2 21 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2008 VL 77 IS 1 BP 27 EP 37 DI 10.1159/000110057 PG 11 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 241NF UT WOS:000251662400005 PM 18087205 ER PT J AU Wittchen, HU Nocon, A Beesdo, K Pine, DS Hofler, M Lieb, R Gloster, AT AF Wittchen, Hans-Ulrich Nocon, Agnes Beesdo, Katja Pine, Daniel S. Hoefler, Michael Lieb, Roselind Gloster, Andrew T. TI Agoraphobia and panic SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE panic disorder; agoraphobia; longitudinal; anxiety; DSM ID NATIONAL-COMORBIDITY-SURVEY; EARLY DEVELOPMENTAL-STAGES; PSYCHIATRIC-DISORDERS; DSM-IV; UNITED-STATES; LIFETIME PREVALENCE; GENERAL-POPULATION; SURVEY REPLICATION; ANXIETY DISORDERS; MENTAL-DISORDERS AB Background: The relationship of panic attacks (PA), panic disorder (PD) and agoraphobia (AG) is controversial. The aim of the current study is to prospectively examine the 10-year natural course of PA, PD and AG in the first three decades of life, their stability and their reciprocal transitions. Methods: DSM-IV syndromes were assessed via Composite International Diagnostic Interview -Munich version in a 10-year prospective-longitudinal community study of 3,021 subjects aged 14 -24 years at baseline. Results: (1) Incidence patterns for PA (9.4%), PD (with and without AG: 3.4%) and AG (5.3%) revealed differences in age of onset, incidence risk and gender differentiation. (2) Temporally primary PA and PD revealed only a moderately increased risk for subsequent onset of AG, and primary AG had an even lower risk for subsequent PA and PD. (3) In strictly prospective analyses, all baseline groups (PA, PD, AG) had low remission rates (0 -23%). Baseline PD with AG or AG with PA were more likely to have follow-up AG, PA and other anxiety disorders and more frequent complications (impairment, disability, help-seeking, comorbidity as compared to PD without AG and AG without PA. Conclusions: Differences in incidence patterns, syndrome progression and outcome, and syndrome stability over time indicate that AG exists as a clinically significant phobic condition independent of PD. The majority of agoraphobic subjects in this community sample never experienced PA, calling into question the current pathogenic assumptions underlying the classification of AG as merely a consequence of panic. The findings point to the necessity of rethinking diagnostic concepts and DSM diagnostic hierarchies. Copyright (C) 2008 S. Karger AG, Basel. C1 [Wittchen, Hans-Ulrich; Beesdo, Katja; Hoefler, Michael; Gloster, Andrew T.] Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, DE-01187 Dresden, Germany. [Wittchen, Hans-Ulrich; Nocon, Agnes; Lieb, Roselind] Max Planck Inst Psychiat, Res Grp Mol Psychol, D-80804 Munich, Germany. [Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, Div Intramural Res Programs, Bethesda, MD 20892 USA. [Lieb, Roselind] Univ Basel, Inst Psychol Epidemiol & Hlth Psychol, Basel, Switzerland. RP Wittchen, HU (reprint author), Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, Chemnitzer Str 46, DE-01187 Dresden, Germany. EM wittchen@psychologie.tu-dresden.de RI Beesdo-Baum, Katja/A-5793-2012; Wittchen, Hans-Ulrich/A-8507-2014 NR 67 TC 59 Z9 60 U1 2 U2 17 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2008 VL 77 IS 3 BP 147 EP 157 DI 10.1159/000116608 PG 11 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 273EB UT WOS:000253912100003 PM 18277061 ER PT J AU Harris, RK Becker, ED De Menezes, SMC Granger, P Hoffman, RE Zilm, KW AF Harris, Robin K. Becker, Edwin D. De Menezes, Sonia M. Cabral Granger, Pierre Hoffman, Roy E. Zilm, Kurt W. TI Further conventions for NMR shielding and chemical shifts (IUPAC recommendations 2008) SO PURE AND APPLIED CHEMISTRY LA English DT Article DE nuclear magnetic resonance; recommendations; chemical shifts; conventions; IUPAC Physical and Biophysical Chemistry Division; shielding tensors ID NUCLEAR-QUADRUPOLE RESONANCE; ABSOLUTE TEMPERATURE-DEPENDENCE; MAGNETIC DIPOLE-MOMENTS; HIGH-RESOLUTION NMR; GAS-PHASE; SUSCEPTIBILITY; TETRAMETHYLSILANE; SPECTRA; STANDARDIZATION; SPECTROSCOPY AB IUPAC has published a number of recommendations regarding the reporting of nuclear magnetic resonance (NMR) data, especially chemical shifts. The most recent publication [Pure Appl. Chem. 73, 1795 (2001)] recommended that tetramethyl si lane (TMS) serve as a universal reference for reporting the shifts of all nuclides, but it deferred recommendations for several aspects of this subject. This document first examines the extent to which the H-1 shielding in TMS itself is subject to change by variation in temperature, concentration, and solvent. On the basis of recently published results, it has been established that the shielding of TMS in solution [along with that of sodium-3-(trimethylsilyl)propanesulfonate, DSS, often used as a reference for aqueous solutions] varies only slightly with temperature but is subject to solvent perturbations of a few tenths of a part per million (ppm). Recommendations are given for reporting chemical shifts under most routine experimental conditions and for quantifying effects of temperature and solvent variation, including the use of magnetic susceptibility corrections and of magic-angle spinning (MAS). This document provides the first IUPAC recommendations for referencing and reporting chemical shifts in solids, based on high-resolution MAS studies. Procedures are given for relating C-13 NMR chemical shifts in solids to the scales used for high-resolution studies in the liquid phase. The notation and terminology used for describing chemical shift and shielding tensors in solids are reviewed in some detail, and recommendations are given for best practice. C1 [Harris, Robin K.] Univ Durham, Dept Chem, Durham DH1 3LE, England. [Becker, Edwin D.] NIH, Bethesda, MD 20892 USA. [De Menezes, Sonia M. Cabral] PETROBRAS CENPES QM, BR-21941598 Rio De Janeiro, Brazil. [Granger, Pierre] Univ Strasbourg 1, Inst Chem, F-67008 Strasbourg, France. [Hoffman, Roy E.] Hebrew Univ Jerusalem, Dept Organ Chem, IL-91904 Jerusalem, Israel. [Zilm, Kurt W.] Yale Univ, Dept Chem, New Haven, CT 06520 USA. RP Harris, RK (reprint author), Univ Durham, Dept Chem, South Rd, Durham DH1 3LE, England. EM r.k.harris@durham.ac.uk NR 44 TC 182 Z9 184 U1 7 U2 63 PU INT UNION PURE APPLIED CHEMISTRY PI RES TRIANGLE PK PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD JAN PY 2008 VL 80 IS 1 BP 59 EP 84 DI 10.1351/pac200880010059 PG 26 WC Chemistry, Multidisciplinary SC Chemistry GA 254AH UT WOS:000252558200005 ER PT J AU Blair, RJR AF Blair, R. J. R. TI Fine cuts of empathy and the amygdala: Dissociable deficits in psychopathy and autism SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT Festschrift held in Honor of Occasion of Uta Friths Retirement CT Royal-Society Conference on Uta Frith CY JAN 02-03, 2007 CY JAN 02-03, 2007 CL Royal Soc, London, ENGLAND CL London, ENGLAND SP Expt Psychol Soc, British Psychol Soc, Univ Coll London, British Acad, Jessica Kingsley Publishers SP Expt Psychol Soc, British Psychol Soc, British Acad, Univ Coll London, Jessica Kingsley Publishers HO Royal Soc ID ANTISOCIAL PERSONALITY-DISORDERS; FACIAL EXPRESSIONS; ASPERGER-SYNDROME; SPECTRUM DISORDER; NEURAL RESPONSES; SOCIAL-BEHAVIOR; RHESUS-MONKEYS; RECOGNITION DEFICITS; FEARFUL EXPRESSIONS; DOMAIN SPECIFICITY AB In the current paper, the "fine cuts" approach advocated by Uta Frith is applied to our understanding of empathy and amygdala dysfunction in two disorders, psychopathy and autism. A fine cut is made between cognitive (i.e., Theory of Mind) and emotional empathy. The literature with respect to psychopathy and autism and these two functions is then considered. A fine cut is also made between the amygdala's role in stimulus-reinforcement association and specific aspects of social cognition. Again the literature with respect to psychopathy and autism and these two functions of the amygdala is considered. It is concluded that while both conditions can be considered disorders of social cognition, fine cuts can be made dissociating the impairments associated with each. C1 NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Program, Room 206,15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov NR 139 TC 99 Z9 99 U1 10 U2 61 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1747-0218 EI 1747-0226 J9 Q J EXP PSYCHOL JI Q. J. Exp. Psychol. PD JAN PY 2008 VL 61 IS 1 BP 157 EP 170 DI 10.1080/17470210701508855 PG 14 WC Psychology, Biological; Physiology; Psychology; Psychology, Experimental SC Psychology; Physiology GA 249HH UT WOS:000252218400013 PM 18038346 ER PT J AU Trzeciak, AR Barnes, J Evans, MK AF Trzeciak, Andrzej R. Barnes, Janice Evans, Michele K. TI A modified alkaline comet assay for measuring DNA repair capacity in human populations SO RADIATION RESEARCH LA English DT Article ID BREAST-CANCER PATIENTS; DOUBLE-STRAND BREAKS; RADIATION-INDUCED APOPTOSIS; PERIPHERAL-BLOOD; IN-VIVO; CRYOPRESERVED LYMPHOCYTES; MUTAGEN SENSITIVITY; IONIZING-RADIATION; SINGLE-STRAND; DAMAGE AB Use of the alkaline comet assay to assess DNA repair capacity in human populations has been limited by several factors, including lack of methodology for use of unstimulated cryopreserved peripheral blood mononuclear cells (PBMCs), insufficient control of interexperimental variability, and limited analysis of DNA repair kinetics. We show that unstimulated cryopreserved PBMCs can be used in DNA repair studies performed using the comet assay. We have applied data standardization for the analysis of DNA repair capacity using negative and positive internal standards as controls for interexperimental variability. Our standardization procedure also uses negative controls, which provides a way to minimize the interference of interindividual variation in baseline DNA damage levels on DNA repair capacity measurements in populations. DNA repair capacity was assessed in a small human cohort using the parameters described in the literature including initial DNA damage, half-time of DNA repair, and residual DNA damage after 30 and 60 min. We have also introduced new DNA repair capacity parameter, initial rate of DNA repair. There was no difference in DNA repair capacity between fresh and cryopreserved PBMCs when measured by the Olive tail moment and tail DNA. The use of DNA repair capacity parameters in assessment of fast and slow single-strand break repair components is discussed. (c) 2008 by Radiation Research Society. C1 [Trzeciak, Andrzej R.; Barnes, Janice; Evans, Michele K.] NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. [Trzeciak, Andrzej R.; Barnes, Janice; Evans, Michele K.] NIH, NIA, Baltimore, MD 21224 USA. RP Evans, MK (reprint author), NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. EM evansmi@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000513-07, ] NR 54 TC 18 Z9 18 U1 0 U2 1 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 2008 VL 169 IS 1 BP 110 EP 121 DI 10.1667/RR1101.1 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 247WH UT WOS:000252112800012 PM 18159959 ER PT J AU Petrella, JR Mattay, VS Doraiswamy, PM AF Petrella, Jeffrey R. Mattay, Venkata S. Doraiswamy, P. Murali TI Imaging genetics of brain longevity and mental wellness: The next frontier? SO RADIOLOGY LA English DT Review ID MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E EPSILON-4; FACTOR VAL66MET POLYMORPHISM; AFFECTS HUMAN-MEMORY; ALZHEIMERS-DISEASE; GROWTH-FACTOR; DOPAMINE TRANSPORTER; PREFRONTAL CORTEX; HUMAN GENOME; SCHIZOPHRENIA AB The advent of new "omics" technologies (genomics, proteomics, and metabolomics) has ushered in a new era of biomedical discovery that is already affecting every field of medicine. With the rapid growth of the older population worldwide, there is great interest in applying these technologies not only to diagnose and prevent disease, but also to enhance brain longevity and mental wellness. Nearly two-thirds of the approximately 30 000 genes in the human genome are related to brain function, and up to half of the variance in age-related changes in cognition, brain volume, and neuronal function appears to be genetically determined. Selected examples will be used to illustrate how neuroimaging is being employed to study the effects of genes and how neurogenetics may affect future radiology research and practice. C1 [Petrella, Jeffrey R.] Duke Univ, Med Ctr, Alzheimer Imaging Res Lab, Dept Radiol, Durham, NC 27710 USA. [Doraiswamy, P. Murali] Duke Univ, Med Ctr, Dept Psychiat & Med, Durham, NC 27710 USA. [Mattay, Venkata S.] NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. RP Petrella, JR (reprint author), Duke Univ, Med Ctr, Alzheimer Imaging Res Lab, Dept Radiol, Box 3808, Durham, NC 27710 USA. EM jeffrey.petrella@duke.edu NR 75 TC 16 Z9 17 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2008 VL 246 IS 1 BP 20 EP 32 DI 10.1148/radiol.2461061994 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JN UT WOS:000252795300006 PM 18096526 ER PT J AU Petrick, N Haider, M Summers, RM Yeshwant, SC Brown, L Iuliano, EM Louie, A Choi, JR Pickhardt, PJ AF Petrick, Nicholas Haider, Maruf Summers, Ronald M. Yeshwant, Srinath C. Brown, Linda Iuliano, Edward M. Louie, Adeline Choi, J. Richard Pickhardt, Perry J. TI CT colonography with computer-aided detection as a second reader: Observer performance study SO RADIOLOGY LA English DT Article; Proceedings Paper CT 91st Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 27-DEC 02, 2005 CL Chicago, IL SP Radiol Soc N Amer ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; POLYP DETECTION; COLONIC POLYPS; LUNG NODULES; POPULATION; FEASIBILITY; DIAGNOSIS; ISSUES; ROC AB Purpose: To evaluate the effect of computer-aided detection (CAD) as second reader on radiologists' diagnostic performance in interpreting computed tomographic (CT) colonographic examinations by using a primary two-dimensional (2D) approach, with segmental, unblinded optical colonoscopy as the reference standard. Materials and Methods: This HIPAA-compliant study was IRB-approved with written informed consent. Four board-certified radiologists analyzed 60 CT examinations with a commercially available review system. Two-dimensional transverse views were used for initial polyp detection, while three-dimensional (3D) endoluminal and 2D multiplanar views were available for problem solving. After initial review without CAD, the reader was shown CAD-identified polyp candidates. The readers were then allowed to add to or modify their original diagnoses. Polyp location, CT Colonography Reporting and Data System categorization, and reader confidence as to the likelihood of a candidate being a polyp were recorded before and after CAD reading. The area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity were estimated for CT examinations with and without CAD readings by using multireader multicase analysis. Results: Use of CAD led to nonsignificant average reader AUC increases of 0.03, 0.03, and 0.04 for patients with adenomatous polyps 6 mm or larger, 6-9 mm, and 10 mm or larger, respectively (P >=.25); likewise, CAD increased average reader sensitivity by 0.15, 0.16, and 0.14 for those respective groups, with a corresponding decrease in specificity of 0.14. These changes achieved significance for the 6 mm or larger group (P <.01), 6-9 mm group (P <.02), and for specificity (P <.01), but not for the 10 mm or larger group (P <.16). The average reading time was 5.1 minutes +/- 3.4 (standard deviation) without CAD. CAD added an average of 3.1 minutes +/- 4.3 (62%) to each reading (supine and prone positions combined); average total reading time, 8.2 minutes +/- 5.8. Conclusion: Use of CAD led to a significant increase in sensitivity for detecting polyps in the 6 mm or larger and 6-9 mm groups at the expense of a similar significant reduction in specificity. C1 [Haider, Maruf; Summers, Ronald M.; Yeshwant, Srinath C.; Brown, Linda; Louie, Adeline] NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Petrick, Nicholas] US FDA, Natl Inst Biomed Imaging & Bioengn, Ctr Devices & Radiol Hlth, Joint Lab Assessment Med Imaging Syst, Rockville, MD USA. [Iuliano, Edward M.] Georgetown Univ, Sch Med, Dept Radiol, Washington, DC USA. [Choi, J. Richard] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. [Pickhardt, Perry J.] Univ Wisconsin, Dept Radiol, Sch Med, Madison, WI 53706 USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bldg 10,Room 1C351, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS NR 22 TC 66 Z9 67 U1 2 U2 7 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2008 VL 246 IS 1 BP 148 EP 156 DI 10.1148/radiol.2453062161 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JN UT WOS:000252795300020 PM 18096536 ER PT J AU Wen, H Marsolo, KA Bennett, EE Kutten, KS Lewis, RP Lipps, DB Epstein, ND Plehn, JF Croisille, P AF Wen, Han Marsolo, Keith A. Bennett, Eric E. Kutten, Kwame S. Lewis, Ryan P. Lipps, David B. Epstein, Neal D. Plehn, Jonathan F. Croisille, Pierre TI Adaptive postprocessing techniques for myocardial tissue tracking with displacement-encoded MR imaging SO RADIOLOGY LA English DT Article ID PHASE-UNWRAPPING ALGORITHM; MAGNETIC-RESONANCE; COMPUTED-TOMOGRAPHY; ACC/AHA GUIDELINES; HEART-ASSOCIATION; MOTION; IMAGES; CONTRAST; OPTIMIZATION; DEFORMATION AB The purpose of this study was to prospectively assess the effects of two adaptive postprocessing techniques on the evaluation of myocardial function with displacement-encoded magnetic resonance (MR) imaging, including sensitivity for abnormal wall motion, with two-dimensional echocardiography as the reference standard. Sixteen patients (11 men, five women; age range, 26-74 years) and 12 volunteers (six men, six women; age range, 29-53 years) underwent breath-hold MR imaging. Institutional review board approval and informed consent were obtained. Adaptive phase-unwrapping and spatial filtering techniques were compared with conventional phase-unwrapping and spatial filtering techniques. Use of the adaptive techniques led to a reduced rate of failure with the phase-unwrapping technique from 18.9% to 0.6% (P < .001), resulted in lower variability of segmental strain measurements among healthy volunteers (P < .001 to P < .02), and increased the sensitivity of quantitative detection of abnormal segments in patients from 82.5% to 87.7% (P = .034). The adaptive techniques improved the semiautomated postprocessing of displacement-encoded cardiac images and increased the sensitivity of detection of abnormal wall motion in patients. (c) RSNA, 2008. C1 [Wen, Han; Bennett, Eric E.; Lewis, Ryan P.; Epstein, Neal D.] Natl Inst Hlth, NHLBI, Bethesda, MD 20892 USA. [Marsolo, Keith A.] Ohio State Univ, Dept Comp Sci & Engn, Columbus, OH USA. [Plehn, Jonathan F.] George Washington Univ, Sch Med, Div Cardiol, Washington, DC USA. [Kutten, Kwame S.] Rensselaer Polytech Inst, Dept Biomed Engn, Troy, NY USA. [Lipps, David B.] Tulane Univ, Dept Biomed Engn, New Orleans, LA 70118 USA. [Croisille, Pierre] Hop Cardiol & Pneumol, Dept Radiol, Lyon, France. RP Wen, H (reprint author), Natl Inst Hlth, NHLBI, Bldg 10,B1D416,10 Ctr Dr, Bethesda, MD 20892 USA. EM wenh@nhlbi.nih.gov RI Lipps, David/A-7080-2013; Lipps, David/C-3964-2014; Croisille, Pierre/H-4928-2014; Wen, Han/G-3081-2010 OI Lipps, David/0000-0003-1140-9891; Croisille, Pierre/0000-0003-4019-3460; Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [ZIA HL004606-13] NR 52 TC 26 Z9 26 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2008 VL 246 IS 1 BP 229 EP 240 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JN UT WOS:000252795300030 PM 18096537 ER PT J AU Gierada, DS Pilgram, TK Ford, M Fagerstrom, RM Church, TR Nath, H Garg, K Strollo, DC AF Gierada, David S. Pilgram, Thomas K. Ford, Melissa Fagerstrom, Richard M. Church, Timothy R. Nath, Hrudaya Garg, Kavita Strollo, Diane C. TI Lung cancer: Interobserver agreement on interpretation of pulmonary findings at low-dose CT screening SO RADIOLOGY LA English DT Article; Proceedings Paper CT 91st Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 27-DEC 02, 2005 CL Chicago, IL SP Radiol Soc N Amer ID SPIRAL COMPUTED-TOMOGRAPHY; INTRAOBSERVER VARIABILITY; RANDOMIZED FEASIBILITY; ASYMPTOMATIC SMOKERS; CHEST RADIOGRAPHY; NODULE DETECTION; ACTION PROJECT; TRIAL; RADIOLOGISTS; DIAGNOSIS AB Purpose: To evaluate agreement among radiologists on the interpretation of pulmonary findings at low-dose computed tomographic (CT) screening examinations for lung cancer. Materials and Methods: Institutional review board approval and informed consent were obtained. HIPAA guidelines were followed. Sixteen radiologists from the 10 National Lung Screening Trial screening centers of the National Cancer Institute's Lung Screening Study network reviewed image subsets from 135 baseline low-dose screening CT examinations in 135 trial participants (89 men, 46 women; mean age, 62.7 years +/- 5.4 [standard deviation]). Interpretations were classified into one of four of the following categories: non-classified nodule 4 mm or larger in greatest transverse dimension (positive screening result); noncalcified nodule smaller than 4 mm in greatest transverse dimension (negative screening result); calcified, benign nodule (negative screening result); or no nodule (negative screening result). A recommendation for follow-up evaluation was obtained for each case. Interobserver agreement was evaluated by using the multirater kappa statistic and by using response frequencies and descriptive statistics. Results: Multirater kappa values ranged from 0.58 (for agreement among all four classifications; 95% confidence interval: 0.55, 0.61) to 0.64 (for agreement on classification as a positive or negative screening result; 95% confidence interval: 0.62, 0.65). The average percentage of reader pairs in agreement on the screening result per case (percentage agreement) was 82%. There was wide variation in the total number of abnormalities detected and classified as pulmonary nodules, with differences of up to more than twofold among radiologists. For cases classified as positive, multirater kappa for follow-up recommendations was 0.35. Conclusion: Interobserver agreement was moderate to substantial; potential for considerable improvement exists. (c) RSNA, 2007. C1 [Gierada, David S.; Pilgram, Thomas K.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63105 USA. [Ford, Melissa] Westat Corp, Rockville, MD USA. [Fagerstrom, Richard M.] Natl Canc Inst, Bethesda, MD USA. [Church, Timothy R.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Nath, Hrudaya] Univ Alabama, Med Sch Birmingham, Tuscaloosa, AL 35487 USA. [Garg, Kavita] Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. [Strollo, Diane C.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Gierada, DS (reprint author), Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, 510 S Kingshighway Blvd, St Louis, MO 63105 USA. EM gieradad@wustl.edu OI Church, Timothy R./0000-0003-3292-5035 FU NCI NIH HHS [N01-CN-25516] NR 41 TC 50 Z9 56 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2008 VL 246 IS 1 BP 265 EP 272 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JN UT WOS:000252795300034 PM 18024436 ER PT J AU Badal, A Kyprianou, L Badano, A Sempau, J AF Badal, Andreu Kyprianou, Lacovos Badano, Aldo Sempau, Josep TI Monte Carlo simulation of a realistic anatomical phantom described by triangle meshes: Application to prostate brachytherapy imaging SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Monte Carlo; PENELOPE; penMesh; triangle mesh; NCAT; computer-aided design ID ESTRO/EAU/EORTC RECOMMENDATIONS; PACKAGE; PHOTON AB Purpose: Monte Carlo codes can simulate the transport of radiation within matter with high accuracy and can be used to study medical applications of ionising radiations. The aim of our work was to develop a Monte Carlo code capable of generating projection images of the human body. In order to obtain clinically realistic images a detailed anthropomorphic phantom was prepared. These two simulation tools are intended to study the multiple applications of imaging in radiotherapy, from image guided treatments to portal imaging. Methods: We adapted the general-purpose code PENELOPE 2006 to simulate a radiation source, an ideal digital detector, and a realistic model of the patient anatomy. The anthropomorphic phantom was developed using computer-aided design tools, and is based on the NCAT phantom. The surface of each organ is modelled using a closed triangle mesh, and the full phantom contains 330 organs and more than 5 million triangles. A novel object-oriented geometry package, which includes an octree structure to sort the triangles, has been developed to use this complex geometry with PENELOPE. Results: As an example of the capabilities of the new code, projection images of the human pelvis region were simulated. Radioactive seeds were included inside the phantom's prostate. Therefore, the resulting simulated images resemble what would be obtained in a clinical procedure to assess the positioning of the seeds in a prostate brachytherapy treatment. Conclusions: The new code can produce projection images of the human body that are comparable to those obtained by a real imaging system (within the limitations of the anatomical phantom and the detector model). The simulated images can be used to study and optimise an imaging task (i.e., maximise the object detectability, minimise the delivered dose, find the optimum beam energy, etc.). Since PENELOPE can simulate radiation from 50 eV to 1 GeV, the code can also be used to simulate radiotherapy treatments and portal imaging. Using the octree data structure, the new geometry model does not significantly increase the computing time when compared to the simulation of a much simpler quadric geometry. In conclusion, we have shown that it is feasible to use PENELOPE and a complex triangle mesh geometry to simulate real medical physics applications. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Badal, Andreu; Sempau, Josep] Univ Politecn Cataluna, Inst Tech Energet, E-08028 Barcelona, Spain. [Kyprianou, Lacovos; Badano, Aldo] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Washington, DC 20204 USA. RP Badal, A (reprint author), Univ Politecn Cataluna, Inst Tech Energet, Avinguda Diagonal 647, E-08028 Barcelona, Spain. EM andreu.badal@upc.edu RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 FU NCI NIH HHS [224-07-6030]; None [224-04-6055]; PHS HHS [224-04-6055, 224-07-6030] NR 17 TC 9 Z9 9 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD JAN PY 2008 VL 86 IS 1 BP 99 EP 103 DI 10.1016/j.radonc.2007.11.009 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 264QG UT WOS:000253303000016 PM 18061695 ER PT B AU Dunson, DB AF Dunson, David B. BE Dunson, DB TI Random Effect and Latent Variable Model Selection Preface SO RANDOM EFFECT AND LATENT VARIABLE MODEL SELECTION SE Lecture Notes in Statistics LA English DT Editorial Material; Book Chapter C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Dunson, DB (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. EM dunson@stat.duke.edu; dunson@stat.duke.edu NR 2 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-76720-8 J9 LECT NOTES STAT PY 2008 VL 192 BP V EP VII D2 10.1007/978-0-387-76721-5 PG 3 WC Statistics & Probability SC Mathematics GA BKF18 UT WOS:000267943100001 ER PT B AU Cai, B Dunson, DB AF Cai, Bo Dunson, David B. BE Dunson, DB TI Bayesian Variable Selection in Generalized Linear Mixed Models SO RANDOM EFFECT AND LATENT VARIABLE MODEL SELECTION SE Lecture Notes in Statistics LA English DT Article; Book Chapter ID LONGITUDINAL DATA; COVARIANCE-SELECTION; HIERARCHICAL-MODELS; COMPONENT; MATRICES C1 [Cai, Bo] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Dunson, David B.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. RP Cai, B (reprint author), Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. EM bocai@gwm.sc.edu NR 36 TC 3 Z9 3 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-76720-8 J9 LECT NOTES STAT PY 2008 VL 192 BP 63 EP 91 D2 10.1007/978-0-387-76721-5 PG 29 WC Statistics & Probability SC Mathematics GA BKF18 UT WOS:000267943100005 ER PT B AU Ghosh, J Dunson, DB AF Ghosh, Joyee Dunson, David B. BE Dunson, DB TI Bayesian Model Selection in Factor Analytic Models SO RANDOM EFFECT AND LATENT VARIABLE MODEL SELECTION SE Lecture Notes in Statistics LA English DT Article; Book Chapter ID APPROXIMATIONS; DIMENSION C1 [Ghosh, Joyee; Dunson, David B.] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA. [Dunson, David B.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Ghosh, J (reprint author), Duke Univ, Dept Stat Sci, Durham, NC 27708 USA. EM joyee@stat.duke.edu; dunson1@niehs.nih.gov; dunson1@niehs.nih.gov NR 28 TC 6 Z9 6 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-76720-8 J9 LECT NOTES STAT PY 2008 VL 192 BP 151 EP 163 D2 10.1007/978-0-387-76721-5 PG 13 WC Statistics & Probability SC Mathematics GA BKF18 UT WOS:000267943100008 ER PT J AU Perdivara, I Sisu, E Sisu, I Dinca, N Tomer, KB Przybylski, M Zamfir, AD AF Perdivara, Irina Sisu, Eugen Sisu, Ioana Dinca, Nicolae Tomer, Kenneth B. Przybylski, Michael Zamfir, Alina D. TI Enhanced electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry of long-chain polysaccharides SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID COIL BLOCK-COPOLYMERS; O-GLCNAC; OLIGOSACCHARIDES; CHROMATOGRAPHY; ACCURACY; DEXTRAN AB A novel strategy was developed to extend the application of electrospray ionization (ESI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) to the analysis of long-chain polysaccharides. High molecular weight polydisperse maltodextrins (poly-alpha(1-4) glucose) and dextrans (poly-alpha(1-6) glucose) were chosen as model compounds in the present study. Increased ionization efficiency of these mixtures in the positive ion mode was achieved upon modification of their reducing end with nitrogen-containing groups. The derivatization method is based on the formation of a new C-N bond between 1,6-hexamethylenediamine (HMD) and the reducing end of the polysaccharide, which exists in solution as an equilibrium between the hemiacetal and the open-ring aldehyde form. To achieve the chemical modification of the reducing end, two synthetic pathways were developed: (D coupling of HMD by reductive amination and (ii) oxidation of the hemiacetal to lactone, followed by ring opening by HMD to yield the maltodextrin lactonamide of 1,6-hexanediamine (HMMD). Amino-functionalized polysaccharides were analyzed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FTICR-MS) in the positive ion mode by direct flow injection. The hexamethylenediamine (HMD) and maltodextrin lactonamide of 1,6-hexanediamine (HMMD) moieties provide increased proton affinities which dramatically improve the detection of the long-chain polysaccharides by FTICR-MS. The present approach allowed for identification of single components in mixtures with prominent heterogeneity in the degree of polymerization (DP), without the need for chromatographic separation prior to MS. The high mass accuracy was essential for the unambiguous characterization of the species observed in the analyzed mixtures. Furthermore, molecular components containing up to 42 glucose residues were detected, representing the largest polysaccharide chains analyzed so far by ESI FTICR-MS. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Perdivara, Irina; Przybylski, Michael] Univ Konstanz, Lab Analy Chem & Biopolymer Struct Anal, Dept Chem, D-7750 Constance, Germany. [Perdivara, Irina; Tomer, Kenneth B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Sisu, Eugen] Victor Babes Univ Med & Pharm, Timisoara, Romania. [Sisu, Eugen; Sisu, Ioana] Acad Romana, Inst Chem, Timisoara, Romania. [Dinca, Nicolae; Zamfir, Alina D.] Aurel Vlaicu Univ Arad, Dept Chem & Biol Sci, Timisoara, Romania. [Zamfir, Alina D.] Natl Inst Res & Dev Electrochem & Condensed Matte, Mass Spectrometry Lab, Timisoara, Romania. RP Zamfir, AD (reprint author), Plautius Andronescu Str 1, RO-300224 Timisoara, Romania. EM zamfir@uav.ro RI Zamfir, Alina/B-6548-2011; Dinca, Nicolae/B-9077-2013; Tomer, Kenneth/E-8018-2013; OI Sisu, Eugen/0000-0002-4530-0272 FU Intramural NIH HHS NR 32 TC 10 Z9 10 U1 3 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2008 VL 22 IS 6 BP 773 EP 782 DI 10.1002/rcm.3435 PG 10 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 282UW UT WOS:000254593700004 PM 18275094 ER PT S AU Vijayasarathy, C Takada, Y Zeng, Y Bush, RA Sieving, PA AF Vijayasarathy, Camasamudram Takada, Yuichiro Zeng, Yong Bush, Ronald A. Sieving, Paul A. BE Anderson, RE LaVail, MM Hollyfield, JG TI Organization and molecular interactions of retinoschisin in photoreceptors SO RECENT ADVANCES IN RETINAL DEGENERATION SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 12th International Symposium on Retinal Degeneration CY OCT, 2006 CL Bariloche, ARGENTINA ID LINKED JUVENILE RETINOSCHISIS; EXTRACELLULAR-MATRIX; MEMBRANE-PROTEIN; GENE; EXPRESSION; MUTATIONS; DISCOIDIN; KNOCKOUT; BINDING; RS1H C1 [Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. RP Sieving, PA (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM camasamudramv@nidcd.nih.gov; pas@nei.nih.gov FU Intramural NIH HHS NR 20 TC 4 Z9 4 U1 0 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-74902-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2008 VL 613 BP 291 EP 297 PG 7 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BHF26 UT WOS:000252649500034 PM 18188957 ER PT S AU Harvey, BK Wang, Y Hoffer, BJ AF Harvey, B. K. Wang, Y. Hoffer, B. J. BE Chiu, WT Kao, MC Hung, CC Lin, SZ Chen, HJ Tang, SFT Hoffer, B Chiang, YH TI Transgenic rodent models of Parkinson's disease SO RECONSTRUCTIVE NEUROSURGERY SE ACTA NEUROCHIRURGICA SUPPLEMENTA LA English DT Proceedings Paper CT 5th Scientific Meeting of the Neurorehabilitation and Reconstructive Neurosurgery Committee of the World-Federation-of-Neurosurgical-Societies held in conjunction with the 2nd Congress of the International-Society-of-Reconstructive-Neurosurgery CY SEP 13-16, 2007 CL Taipei, TAIWAN SP World Federat Neurosurg Soc, Neurorehabilitat & Reconstruct Neurosurg Comm, Int Soc Reconstruct Neurosurg DE Parkinson's disease; DJ-1; PINK1; parkin; transgenic; mitopark ID EARLY-ONSET PARKINSONISM; UBIQUITIN-PROTEIN LIGASE; DEFICIENT MICE; PINK1 MUTATIONS; MITOCHONDRIAL DYSFUNCTION; RECESSIVE PARKINSONISM; DOPAMINE RELEASE; DJ-1 MUTATIONS; NULL MICE; GENE AB In the case of Parkinson's disease (PD), classical animal models have utilized dopaminergic neurotoxins such as 6-hydroxydopamine (6OHDA) and 1-methyl 4-phenyl 1.2.3.6-tetrahydropyrindine (MPTP). more recently, human genetic linkage studies have identified several genes in familial forms of PD. Transgenic models have been made that explore the function of PD-linked genes (e.g. 0-synuclein, DJ-1. LRRK2. Parkin, UCII-L1. PINK1). Recent evidence suggests mitochondrial dysfunction may play a major role in PD. Manipulation of mitochondrial repiratory genes (e.g. mitochondrial transcription factor A or TFAM) also elicits a PD phenotype in mice. Transgenic mice (MitoPark) were developed that have TFAM selectively knocked cut in dopaminergic neurons. The nigral dopamine neurons of MitoPark mice show respiratory chain dysfunction, accompanied by the development of intrancuronal inclusions and eventual cell death. In early adulthood, the MitoPark mice show a slowly progressing loss of motor function that accompanies these cellular chage. The MitoPark mouse enables further study of the role of miochondrial dysfunction in DA neurons as an important mechanism in the development of PD. Transgenic technology has allowed new insights into mechanisms of neurodegeneration for a number of neurological disorders. This paper will summarize recent studies on several transgenic models of PD. C1 [Harvey, B. K.; Wang, Y.; Hoffer, B. J.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Hoffer, BJ (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RI Harvey, Brandon/A-5559-2010 FU Intramural NIH HHS [Z99 DA999999, Z01 DA000443-07] NR 47 TC 26 Z9 28 U1 0 U2 2 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 978-3-211-78204-0 J9 ACT NEUR S JI Acta Neurochir. Suppl. PY 2008 VL 101 BP 89 EP 92 PG 4 WC Surgery SC Surgery GA BID05 UT WOS:000258497500015 PM 18642640 ER PT S AU Chou, J Harvey, BK Ebendal, T Hoffer, B Wang, Y AF Chou, J. Harvey, B. K. Ebendal, T. Hoffer, B. Wang, Y. BE Chiu, WT Kao, MC Hung, CC Lin, SZ Chen, HJ Tang, SFT Hoffer, B Chiang, YH TI Nigrostriatal alterations in bone morphogenetic protein receptor II dominant negative mice SO RECONSTRUCTIVE NEUROSURGERY SE Acta Neurochirurgica Supplementum LA English DT Proceedings Paper CT 5th Scientific Meeting of the Neurorehabilitation and Reconstructive Neurosurgery Committee of the World-Federation-of-Neurosurgical-Societies CY SEP 13-16, 2007 CL Taipei, TAIWAN SP World Federat Neurosurg Soc, Neurorehabilitat & Reconstruct Neurosurg Comm, Int Soc Reconstruct Neurosurg DE bone morphogenetic protein; BMPRII; mecthamphet-amine; apoptosis ID BRAIN; EXPRESSION AB Background. We previously demonstrated that exogenous application of bone morphogenetic protein 7 (BMP7) reduced 6-hydroxydopamine-mediated neurodegrneration in a redent model of Parkinson's disease. The purpose of this study is to examine the endogenous neurotrophic properties of BMP Receptor II in dopaminergic neurons of the nigrostriatal pathway. Methods. Adult male BMPRII dominant negative (BMPRIIDN) mice and their wild type controles (WT) were placed in the activity chambers for 3 days to monitor ocomotor activity. Animals were sacrificed for tyrosine hydroxylase (TH) immunostaining. A subgroup of BMPRIIDN and WT mice were injected with high doses of methamphetamine (MA) and were sacrificed for terminal deoxy-nucleotidel transferase-mediate dUTP nick-end labeling (TUNEL) histochemistry at 4 days after injection. Results. BMPRIIDN mine had lower locomotor activity than the WT. There is a significant decrease in TH neuronal number in substantianigra compacta. TH fiber density in the substantia nigra reticulata, and TH immunoreactivity in striatum in the BMPRIIDN mice, suggesting that definciency in endogenous BMP signaling reduces dopaminergic innervation and motor function in the nigrostriatal pathway. Administration of MA increased TUNEL labeling in the substantia nigra in the BMPRIIDN mice. Conclusions. Endogenous BMPs have trophic effects on nigrostriatal dopaminergic neurons. Deficiency in BMP signaling increases vulnerability to insults induced by high doses of MA. C1 [Chou, J.; Harvey, B. K.; Hoffer, B.; Wang, Y.] Natl Inst Drug Abuse, Neural Protect & Regenerat Sect, NIH, IRP 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. [Ebendal, T.] Uppsala Univ, BMC, Dept Neurosci, Uppsala, Sweden. RP Wang, Y (reprint author), Natl Inst Drug Abuse, Neural Protect & Regenerat Sect, NIH, IRP 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ywang@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000429-09] NR 9 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 978-3-211-78204-0 J9 ACTA NEUROCHIR SUPPL JI Acta Neurochir. Suppl. PY 2008 VL 101 BP 93 EP + PG 2 WC Surgery SC Surgery GA BID05 UT WOS:000258497500016 PM 18642641 ER PT J AU Cokic, VP Schechtert, AN AF Cokic, Vladan P. Schechtert, Alan N. TI Effects of nitric oxide on red blood cell development and phenotype SO RED CELL DEVELOPMENT SE CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY LA English DT Review ID SOLUBLE GUANYLATE-CYCLASE; ACTIVATED PROTEIN-KINASE; GLOBIN GENE-EXPRESSION; NECROSIS-FACTOR-ALPHA; VASCULAR SMOOTH-MUSCLE; HEMATOPOIETIC PROGENITOR CELLS; UBIQUITIN-PROTEASOME PATHWAY; FETAL-HEMOGLOBIN INDUCTION; COLONY-STIMULATING FACTORS; ENDOTHELIAL GROWTH-FACTOR AB Nitric oxide (NO) is a diffusible free radical generated primarily by NO synthases (NOS), isoenzymes that convert the L-arginine and molecular oxygen to citrulline and NO in cells. Endothelial cells as well as macrophages, components of hematopoietic microenvironment and potent NO producers, play an active role in the modulation of human hematopoietic cell growth and differentiation. A role of NO in erythroid cell differentiation has been postulated based on demonstration that NO inhibits growth, differentiation, and hemoglobinization of erythroid primary cells. Endothelial NOS (eNOS) mRNA and protein levels, as well as bioactivity, decrease during erythroid differentiation, concomitantly with the elevation of hemoglobin levels. Human red blood cells (RBCs) have been reported to contain some eNOS activity; NO appears to affect RBC's deformability. Generally, NO activates cellular soluble guanylyl cyclase (sGC) to produce a second messenger molecule cGMR NO increases cGMP, gamma-globin, and HbF levels in human erythroid cells whereas inhibition of sGC prevents NO-induced increase in gamma-globin gene expression. Activation of sGC increases gamma-globin gene expression in primary human erythroblasts. High cAMP levels continuously decrease in contrast to steady but low levels of cGMP during erythroid differentiation. The activation of the cAMP pathway has also been reported to induce expression of the gamma-globin gene in human erythroid cells. NO is hydrophobic and accumulates in lipid membranes, and most autoxidation to nitrite in vivo occurs there. The reaction of NO with deoxyhemoglobin produces nitrosythemoglobin (HbFe(II)NO), while that with oxyhemoglobin produced methemoglobin and nitrate. Nitrite can also react with deoxyhemoglobin to produce NO. This reaction as well as the postulated formation of a thiot-NO derivative of hemoglobin (SNO-Hb) appears to be major mechanisms for the preservation and transport of NO bioactivity by red cells-making NO act as a "hormone." Thus, RBCs and hemoglobin molecules are essential factors in regulating the bioactivity of NO throughout the mammalian body and may be important in the pathophysiology of several circulatory diseases and be the basis for new therapeutic approaches to these diseases. C1 [Cokic, Vladan P.] Med Res Inst, Lab Expt Hematol, Belgrade, Serbia. [Schechtert, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Cokic, VP (reprint author), Med Res Inst, Lab Expt Hematol, Belgrade, Serbia. OI Schechter, Alan N/0000-0002-5235-9408 NR 258 TC 8 Z9 10 U1 1 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 J9 CURR TOP DEV BIOL PY 2008 VL 82 BP 169 EP + DI 10.1016/S0070-2153(07)00007-5 PG 50 WC Developmental Biology SC Developmental Biology GA BHN05 UT WOS:000254417500007 PM 18282521 ER PT J AU Kaler, SG AF Kaler, Stephen G. TI Diseases of poverty with high mortality in infants and children - Malaria, measles, lower respiratory infections, and diarrheal illnesses SO REDUCING THE IMPACT OF POVERTY ON HEALTH AND HUMAN DEVELOPMENT: SCIENTIFIC APPROACHES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE malaria; measles; genotype; pneumonia; diarrhea; undernutrition ID PNEUMOCOCCAL CONJUGATE VACCINE; PNEUMONIA; AFRICA; BURDEN; IMPACT; VIRUS; WORLD AB Malaria, measles, lower respiratory infections, and diarrheal illnesses are common pediatric medical problems that are often fatal in the context of extreme poverty. In nonpoor environments, however, these infections are controlled and managed in ways that minimize mortality. From a scientific perspective, genetic variation among microbes is a frequent and important component of their epidemiology, pathophysiology, treatment, and prevention. From a public health perspective, relatively simple measures can reduce the mortal effects of these diseases until successful vaccines become available and immunizations programs are established. Infants and children are especially vulnerable to poor outcomes from infections when undernutrition and other circumstances of poverty are present. C1 Eunice Kennedy Shriver NICHHD, Unit Pediat Genet, Program Mol Med, NIH, Bethesda, MD 20892 USA. RP Kaler, SG (reprint author), Eunice Kennedy Shriver NICHHD, Unit Pediat Genet, Program Mol Med, NIH, 10 Ctr Dr,Rm 5-2571,MSC 1832, Bethesda, MD 20892 USA. EM kalers@mail.nih.gov NR 24 TC 9 Z9 10 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1136 BP 28 EP 31 DI 10.1196/annals.1425.035 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHY28 UT WOS:000257430500004 PM 18579873 ER PT J AU Clark, RL King, RB AF Clark, Rebecca L. King, Rosalind Berkowitz TI Social and economic aspects of immigration SO REDUCING THE IMPACT OF POVERTY ON HEALTH AND HUMAN DEVELOPMENT: SCIENTIFIC APPROACHES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE socioeconomic status; immigrants; children of immigrants; legal immigrants; poverty ID UNDOCUMENTED IMMIGRANTS; OCCUPATIONAL-STATUS; UNITED-STATES; ASSIMILATION; CHILDREN; POPULATION; ETHNICITY; GENDER; TRENDS AB The absolute size of the foreign-born U.S. population is at a historical high, but neither the share of the population that is foreign born nor the share of children in immigrant families is high compared with the beginning of the 20th century. While poverty rates for immigrants and children in immigrant families are substantial, poverty is concentrated among certain groups, particularly Hispanics and blacks, non-citizens, and recent arrivals. The general economic well-being of immigrants improves with the move to the United States and as time in the United States increases. However, immigrants remain disadvantaged in terms of health insurance coverage. The economic situation of children in immigrant families has declined since the late 1960s, despite the high labor force participation of immigrant men and the lower prevalence of single-parent households among immigrant families. Still, children in immigrant families are at least as healthy as children in native families and are less likely to engage in risky behaviors. With socioeconomic factors taken into account, children in immigrant families do as well as other children in school. Analyses of the socioeconomic well-being of immigrants have been hampered by lack of information in major data sets about legal status and about the visa status of legally present immigrants, as well as by limited availability of longitudinal data. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Bethesda, MD 20814 USA. US Dept Hlth & Human Serv, Washington, DC 20201 USA. RP Clark, RL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, 6100 Execut Blvd Room 8B07F MSC 7510, Bethesda, MD 20814 USA. EM rclark@mail.nih.gov NR 43 TC 8 Z9 8 U1 5 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1136 BP 289 EP 297 DI 10.1196/annals.1425.021 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BHY28 UT WOS:000257430500029 PM 18579888 ER PT J AU Bytautiene, E Vedernikov, YP Saade, GR Romero, R Garfield, RE AF Bytautiene, Egle Vedernikov, Yurl P. Saade, George R. Romero, Roberto Garfield, Robert E. TI The effect of a mast cell degranulating agent on vascular resistance in the human placental vascular bed and on the tone of water placental vessels SO REPRODUCTIVE SCIENCES LA English DT Article DE mast cells; placenta; chorionic vessels; human; pregnancy ID INTRAUTERINE GROWTH RESTRICTION; PIG PULMONARY-ARTERY; UTERINE ARTERY; PROSTANOID RECEPTORS; CHORIONIC VEINS; IN-VITRO; HISTAMINE; CONTRACTION; PROSTAGLANDIN-F2-ALPHA; PREECLAMPSIA AB The objective of this study is to investigate the effect of a mast cell degranulating agent, compound 48180, on vascular resistance in the perfused human placenta and on the tone of isolated human chorionic vessels. Human placenta was obtained from term nonlaboring women undergoing cesarean delivery. Placental vascular bed perfusion pressure and isometric tension for sigments of chorionic plate artery and vein were obtained in response to potassium chloride, compound 48180, a mast cell stabilizer (cromolyn), and thromboxane A2 mimetic (U46619). Compound 48180 significantly increased perfusion pressure in isolated human placental cotyledons. This effect was significantly potentiated further after induction of active vascular tone by thromboxane A2 mimetic U46619. Cromolyn significantly attenuated responses to compound 48180 in these preparations. Compound 48180 also significantly increased tone in isolated human chorionic artery and vein rings, and responses were abolished by cromolyn. In conclusion, degranulation of placental and intravascular mast cells by compound 48180 leads to the release of vasoconstrictive substances. This could impair placental blood flow and result in growth restriction in fetuses of women with type 1 hypersensitivity reactions. C1 [Bytautiene, Egle; Vedernikov, Yurl P.; Saade, George R.; Garfield, Robert E.] Univ Texas Galveston, Med Branch, Dept Obstet & Gynaecol, Galveston, TX 77555 USA. [Romero, Roberto] NICHHD, Perinatol Res Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bytautiene, E (reprint author), Univ Texas Galveston, Med Branch, Dept Obstet & Gynaecol, 301 Univ Blvd,Rt J-62, Galveston, TX 77555 USA. EM egbytaut@utmb.edu NR 28 TC 3 Z9 3 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD JAN PY 2008 VL 15 IS 1 BP 26 EP 32 DI 10.1177/1933719107309645 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 255CD UT WOS:000252633400005 PM 18212351 ER PT S AU Zhang, Y Song, G Vinar, T Green, ED Siepel, A Miller, W AF Zhang, Yu Song, Giltae Vinar, Tomas Green, Eric D. Siepel, Adam Miller, Webb BE Vingron, M Wong, L TI Reconstructing the evolutionary history of complex human gene clusters SO RESEARCH IN COMPUTATIONAL MOLECULAR BIOLOGY, PROCEEDINGS SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 12th Annual International Conference on Research Computational Molecular Biology CY MAR 30-APR 02, 2008 CL Singapore, SINGAPORE SP Natl Univ Singapore, NUS Bioinformat Programme, Lilly, IBM, ISCB, World Sci, Taylor & Francis ID TANDEMLY REPEATED GENES; HUMAN GENOME; SEQUENCE; IDENTIFICATION; DUPLICATION; ALIGNMENTS; DIVERGENCE; DATABASE; MOUSE AB Clusters of genes that evolved from single progenitors via repeated segmental duplications present significant challenges to the generation of a truly complete human genome sequence. Such clusters can confound both accurate sequence assembly and downstream computational analysis, yet tliey represent a hotbed of functional innovation, making them of extreme interest. We have developed an algorithm for reconstructing the evolutionary history of gene clusters using only human genomic sequence data. This method allows the tempo of large-scale evolutionary events in human gene clusters to be estimated, which in turn will facilitate primate comparative sequencing studies that will aim to reconstruct their evolutionary history more fully. C1 [Zhang, Yu; Song, Giltae; Miller, Webb] Penn State Univ, Ctr Comparat Genom & Bioinformat, 506B Wartik Lab, University Pk, PA 16802 USA. [Zhang, Yu] Penn State Univ, Dept Stat, University Pk, PA 16802 USA. [Vinar, Tomas; Siepel, Adam] Cornell Univ, Dept Biol Stat & Comp Biol, Ithaca, NY 14853 USA. [Green, Eric D.] Natl Inst Hlth, Natl Human Genome Res Inst, Genome Technol Branch & NIH Intramural Sequencing, Bethesda, MD 20892 USA. RP Zhang, Y (reprint author), Penn State Univ, Ctr Comparat Genom & Bioinformat, 506B Wartik Lab, University Pk, PA 16802 USA. RI Vinar, Tomas/I-3695-2014; OI Vinar, Tomas/0000-0003-3898-3447; Song, Giltae/0000-0001-8796-4678 NR 27 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-78838-6 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2008 VL 4955 BP 29 EP + PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Information Systems; Mathematical & Computational Biology; Mathematics, Applied SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology; Mathematics GA BHM89 UT WOS:000254391500003 ER PT J AU Giger, RJ Venkatesh, K Chivatakarn, O Raiker, SJ Robak, L Hofer, T Lee, HJ Rader, C AF Giger, Roman J. Venkatesh, Karthik Chivatakarn, Onanong Raiker, Stephen J. Robak, Laurie Hofer, Thomas Lee, Hakjoo Rader, Christoph TI Mechanisms of CNS myelin inhibition: Evidence for distinct and neuronal cell type specific receptor systems SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Review DE spinal cord injury; myelin associated glycoprotein; Nogo-A; receptor; NgR1; NgR2; integrin; ganglioside ID CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD-INJURY; NEURITE GROWTH-INHIBITORS; ACID-BINDING-SITE; CORTICOSPINAL TRACT LESIONS; P75 NEUROTROPHIN RECEPTOR; NOGO-66 RECEPTOR; AXONAL REGENERATION; WALLERIAN DEGENERATION; FUNCTIONAL RECOVERY AB Following injury to the adult mammalian central nervous system, regenerative growth of severed axons is very limited. The lack of neuronal repair is often associated with significant functional deficits, and depending on the severity of injury, may result in permanent paralysis distal to the site of injury. A detailed understanding of the molecular mechanisms that limit neuronal growth in the injured spinal cord is an important step toward the development of specific strategies aimed at restoring functional connectivity lost as a consequence of injury. While rapid progress is being made in defining the molecular identity of CNS growth inhibitory constituents, comparatively little is known about their receptors and downstream signaling mechanisms. Emerging new evidence suggests that the mechanisms for myelin inhibition are likely to be complex, involving multiple and distinct receptor systems that may operate in a redundant manner. Furthermore, the relative contribution of a specific ligand-receptor system to bring about growth inhibition may greatly vary among different neuronal cell types. Myelin-associated glycoprotein (MAG), for example, employs different mechanisms to inhibit neurite outgrowth of cerebellar, sensory, and retinal ganglion neurons in vitro. Nogo-A harbors distinct growth inhibitory regions, which employ different signaling mechanisms. The Nogo-66 receptor 1 (NgR1), a shared ligand binding component in a receptor complex for Nogo-66, MAG, and OMgp, participates in neuronal growth cone collapse to acutely presented myelin inhibitors, but is dispensable for longitudinal neurite outgrowth inhibition on substrate-bound Nogo-66, MAG, OMgp, or crude CNS myelin in vitro. Consistent with the idea of cell-type specific mechanisms for myelin inhibition, different types of CNS neurons possess very different regenerative capacities and respond differently to experimental treatment strategies in vivo. We speculate that differences in regenerative axonal growth among different fiber systems are a reflection of their intrinsic ability to elongate axons and their distinct cell surface receptor profiles to respond to the growth inhibitory extracellular milieu. The existence of cell type specific mechanisms to impair regenerative axonal growth in the CNS may have important implications for the development of treatment strategies. Depending on the fiber tract injured, different ligand-receptor systems may need to be targeted in order to elicit robust and long-distance regenerative axonal growth. C1 [Giger, Roman J.; Chivatakarn, Onanong; Raiker, Stephen J.; Robak, Laurie; Lee, Hakjoo] Univ Rochester, Sch Med & Dent, Dept Biomed Genet, Ctr Neural Dev & Disorder, Rochester, NY 14642 USA. [Hofer, Thomas; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Venkatesh, Karthik] Univ Michigan, Multiple Sclerosis Ctr, Holtom Garrett Program Neuroimmunol, Ann Arbor, MI 48109 USA. RP Giger, RJ (reprint author), Univ Rochester, Sch Med & Dent, Dept Biomed Genet, Ctr Neural Dev & Disorder, 601 Elmwood Ave, Rochester, NY 14642 USA. EM Roman_Giger@URMC.Rochester.edu FU New York State Spinal Cord Injury Research Program; National Research Service Award Ruth Kirschstein Fellowship [F31NS056558, F31NS07489]; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation's Adelson Program in Neural Repair and Rehabilitation (APNRR); National Institute of Neurological Disorders and Stroke [NS047333] FX We thank Marc Tessier- Lavigne for the NgR1taulacZ mice. Current support, the New York State Spinal Cord Injury Research Program (R.J.G. and C.R.), National Research Service Award Ruth Kirschstein Fellowship F31NS056558 (O.C.) and F31NS07489 (K.V.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation's Adelson Program in Neural Repair and Rehabilitation (APNRR), National Institute of Neurological Disorders and Stroke NS047333 (R.J.G.). NR 150 TC 50 Z9 57 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2008 VL 26 IS 2-3 BP 97 EP 115 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 355QH UT WOS:000259722900004 PM 18820405 ER PT J AU Vazin, T Chen, J Spivak, CE Amable, R Gabitzsch, E Lee, CT Lupica, CR Freed, WJ AF Vazin, Tandis Chen, Jia Spivak, Charles E. Amable, Rose Gabitzsch, Emily Lee, Chun-Ting Lupica, Carl R. Freed, William J. TI Dopaminergic neurons derived from BG01V2, a variant of human embryonic stem cell line BG01 SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE SDIA; embryonic stem cells; human; dopaminergic neuron; PA6 cells; BG01V2; trisomy 17; stem cell ID SODIUM-CHANNELS; CEREBELLUM DEVELOPMENT; ES CELLS; MIDBRAIN; DIFFERENTIATION; CULTURE; GENE; SPECIFICATION; INDUCTION; STABILITY AB Background and Purpose: Human embryonic stem cells (hESC) are considered a renewable source of dopamine producing neurons, and are of particular interest for their potential clinical use in Parkinson's disease. In this study, we characterized human dopaminergic neurons generated by stromal-derived inducing activity (SDIA) from BG01V2, a strain of human embryonic stem cell line, BG01, characterized by a chromosome 17 trisomy. Similar chromosomal changes have been repeatedly observed in hESC cultures in different laboratories, indicating the importance of chromosome 17 for growth and adaptation of hESC to culture. Methods: We investigated in vitro proliferation of differentiating cells using a BrDU incorporation assay, and monitored the cell population in long term cultures. Despite the cytogenetic abnormality, TH+ neurons were postmitotic at all stages of differentiation. After 30 days of differentiation, cell division ceased in 91% of the overall population of cells in the culture, indicating intact cell cycle regulation. Results: Expression of midbrain specific marker genes (Otx2, Pax5, Msx-1) showed differentiation of hESC-derived neural progenitor cells into midbrain specific dopamine neurons. These neurons expressed the dopamine transporter (DAT), and displayed functional DAT activity and electrical excitability. Conclusions: TH+ cells derived from the BG01V2 hESC line using SDIA are postmitotic and have functional characteristics of normal dopaminergic neurons. C1 [Vazin, Tandis; Chen, Jia; Amable, Rose; Gabitzsch, Emily; Lee, Chun-Ting; Freed, William J.] Natl Inst Drug Abuse, Dev & Plast Sect, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Spivak, Charles E.; Lupica, Carl R.] Natl Inst Drug Abuse, Cellular Neurophysiol Sect, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Vazin, Tandis] AlbaNova Univ Ctr, Royal Inst Technol, KTH, Dept Gene Technol,Sch Biotechnol, Stockholm, Sweden. RP Vazin, T (reprint author), Natl Inst Drug Abuse, Dev & Plast Sect, Cellular Neurobiol Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 333 Cassell Dr,Triad Bldg,Room 3303, Baltimore, MD 21224 USA. EM vazint@mail.nih.gov FU NIDA, NIH, DHHS FX Research supported by the Intramural Research Program of NIDA, NIH, DHHS. NR 43 TC 8 Z9 8 U1 0 U2 13 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2008 VL 26 IS 6 BP 447 EP 458 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 390KO UT WOS:000262162900001 PM 19096132 ER PT B AU Amaral, J Becerra, SP AF Amaral, Juan Becerra, S. Patricia BE Penn, JS TI Pigment epithelium-derived factor and angiogenesis - Therapeutic implications SO RETINAL AND CHOROIDAL ANGIOGENESIS LA English DT Proceedings Paper CT Retinal and Choroidal Angiogenesis Scientific Symposium CY OCT 15-16, 2005 CL Nashville, TN ID ENDOTHELIAL GROWTH-FACTOR; INHIBITS CHOROIDAL NEOVASCULARIZATION; CEREBELLAR GRANULE CELLS; INTRAOCULAR GENE-TRANSFER; FACTOR PEDF; NEUROTROPHIC ACTIVITY; DIABETIC-RETINOPATHY; CRYSTAL-STRUCTURE; AQUEOUS-HUMOR; IN-VIVO AB Pigment epithelium-derived factor (PEDF), an extracellular glycoprotein of 50 kDa, is one of the main anti-angiogenic factors of the eye. Its main source is the retinal pigment epithelium, from which the mature protein is secreted in a polarized fashion toward the retina. PEDF is present at high concentrations in the interphotoreceptor matrix, the vitreous and the aqueous humor. Pathologies like retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration lead to severe visual loss due to neovessel formation and are accompanied by decreases in PEDF levels during their active phase. Pathological generation of blood vessels is also a key component of the growth and spread of tumors. Two of the main steps in the process of angiogenesis are endothelial cell migration and proliferation. PEDF has been shown to inhibit both, and to induce apoptotic endothelial cell death. These observations have led to its use as an anti-angiogenic substance, not only in animal models of eye diseases but also in clinical trials. Viral-mediated gene transfer, genetically engineered cells, and protein delivery systems located in the periocular or intraocular compartments are used to deliver PEDF to its target. PEDF is well tolerated and targets only new vessel formation. This chapter discusses the effects of PEDF in angiogenic models and the different approaches used in its delivery for the treatment of angiogenic eye diseases. C1 [Amaral, Juan; Becerra, S. Patricia] NEI, NIH, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. RP Amaral, J (reprint author), NEI, NIH, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. NR 103 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-1-4020-6779-2 PY 2008 BP 311 EP 337 DI 10.1007/978-1-4020-6780-8_17 PG 27 WC Ophthalmology SC Ophthalmology GA BHM98 UT WOS:000254410500017 ER PT J AU Davis, M Antoniadis, EA Amaral, DG Winslow, JT AF Davis, Michael Antoniadis, Elena A. Amaral, David G. Winslow, James T. TI Acoustic startle reflex in rhesus monkeys: A review SO REVIEWS IN THE NEUROSCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Primate Models for Psychiatric Disorder held at the 16th International Behavioral Neuroscience Meeting CY JUN, 2007 CL Joao Pressoa, BRAZIL DE fear; habituation; prepulse inhibition; amygdala; conditioned inhibition; rhesus monkey ID FEAR-POTENTIATED STARTLE; CONDITIONED FEAR; ANIMAL-MODELS; BASOLATERAL AMYGDALA; MACACA-MULATTA; PARADIGM; LESIONS; INHIBITION; NUCLEUS; ANXIETY AB Modulation of the acoustic startle response is a simple and objective indicator of emotionality and attention in rodents and humans. This finding has proven extremely valuable for the analysis of neural systems associated with fear and anxiety. Until recently, there have been few efforts to develop acoustic startle measurement in non-human primates. Here we review recent work in which whole body acoustic startle amplitude has been measured in rhesus monkeys. Initial studies revealed that the amplitude of whole body startle in monkeys, as in rodents and humans, is directly proportional to acoustic stimulus intensity and gradually habituates with repeated exposures. Presentation of a weak acoustic stimulus 25-5,000 msec before a startle stimulus reduces startle amplitude by 40-50% depending on inter-stimulus interval. length (prepulse inhibition). We have also measured significant fear-potentiated startle in the presence of a visual stimulus after pairing it with an inescapable pulse of pressurized air (fear-potentiated startle). This effect was reduced by diazepam and morphine, but not by buspirone. Ibotenic acid-induced lesions of the amygdala prevented the acquisition of fear-potentiated startle but, remarkably, did not prevent the expression of fear-potentiated startle when fear conditioning was carried out prior to the lesion. Finally, we have developed an objective measure of fear inhibition in monkeys using a novel conditioned inhibition procedure identical to one used in rats and humans. Our data demonstrate that acoustic startle in, non-human primates successfully bridges rodent and human research. The opportunity now emerges to link concepts developed in rodents to the more complex neuroanatomical and cognitive processes common to monkeys and humans. C1 [Davis, Michael] Emory Clin, Yerkes Reg Primate Res Ctr, Dept Psychiat & Behav Sci, Ctr Behav Neurosci, Atlanta, GA 30322 USA. [Antoniadis, Elena A.; Amaral, David G.] Univ Calif Davis, Med Invest Neurodev Disorders Inst, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. Univ Calif Davis, Med Invest Neurodev Disorders Inst, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Winslow, James T.] NIMH, Bethesda, MD 20892 USA. RP Davis, M (reprint author), Emory Clin, Yerkes Reg Primate Res Ctr, Dept Psychiat & Behav Sci, Ctr Behav Neurosci, 954 Gatewood Rd, Atlanta, GA 30322 USA. EM mdavis4@emory.edu FU Intramural NIH HHS; NCRR NIH HHS [RR00165, RR00169]; NIMH NIH HHS [R37 MH057502, MH 057502, MH 47840, MH 58922, R37 MH057502-11] NR 46 TC 37 Z9 38 U1 3 U2 18 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2008 VL 19 IS 2-3 BP 171 EP 185 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 334RX UT WOS:000258240000009 PM 18751523 ER PT J AU Geisler, S Wise, RA AF Geisler, Stefanie Wise, Roy A. TI Functional Implications of Glutamatergic Projections to the Ventral Tegmental Area SO REVIEWS IN THE NEUROSCIENCES LA English DT Review DE dopamine; reward; addiction; network; afferents; lateral hypothalamus; prefrontal cortex ID MIDBRAIN DOPAMINE NEURONS; NUCLEUS-ACCUMBENS DOPAMINE; METHYL-D-ASPARTATE; CORTICOTROPIN-RELEASING-FACTOR; HYPOTHALAMIC OREXIN NEURONS; LONG-TERM POTENTIATION; STRESS-INDUCED RELAPSE; IN-SITU HYBRIDIZATION; RAT SUBSTANTIA-NIGRA; CRF-BINDING-PROTEIN AB Glutamatergic afferents of the ventral tegmental area (VTA) play an important role in the functioning of the VTA and are involved in the pathophysiology of drug addiction. It has recently been demonstrated that the VTA is densely innervated by glutamatergic axons and that glutamatergic neurons projecting to the VTA are situated in almost all structures that project there. While the projection from the prefrontal cortex is essentially entirely glutamatergic, subcortical glutamatergic neurons innervating the VTA intermingle with non-glutamatergic, most likely GABAergic and/or peptidergic VTA-projecting neurons. The first part of this review focuses on the origins and putative functional implications of various glutamatergic projections to the VTA. In the second part we consider how different neuropeptides via different mechanisms modulate glutamatergic actions in the VTA. We conclude by developing a model of how the glutamatergic afferents might together contribute to the functions of the VTA. C1 [Geisler, Stefanie; Wise, Roy A.] Natl Inst Drug Abuse, Behav Neurosci Branch, Dept Hlth & Human Serv, NIH,Intramural Res Program, Baltimore, MD 21224 USA. RP Geisler, S (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Dept Hlth & Human Serv, NIH,Intramural Res Program, 251 Bayview Blvd,Suite 200,R 08A729, Baltimore, MD 21224 USA. EM GeislerS@mail.nih.gov FU NIDA/NIH/DHHS FX The authors wish to thank Daniel S. Zahm for many stimulating discussions about the ideas conveyed herein. The authors were supported by intramural funds from NIDA/NIH/DHHS. NR 192 TC 47 Z9 48 U1 1 U2 7 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0334-1763 EI 1607-8470 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2008 VL 19 IS 4-5 BP 227 EP 244 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 380OV UT WOS:000261475900003 PM 19145985 ER PT J AU Maguire, BA Wondrack, LM Contillo, LG Xu, ZY AF Maguire, Bruce A. Wondrack, Lillian M. Contillo, Leonard G. Xu, Zuoyu TI A novel chromatography system to isolate active ribosomes from pathogenic bacteria SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE ribosomes; chromatography; purification; pathogens ID ESCHERICHIA-COLI; AFFINITY PURIFICATION; CRYSTAL-STRUCTURE; NUCLEIC-ACIDS; TRANSFER-RNA; SEPARATION; SUBUNITS; COMPLEX AB We have developed a novel chromatography for the rapid isolation of active ribosomes from bacteria without the use of harsh conditions or lengthy procedures that damage ribosomes. Ribosomes interact with an alkyl linker attached to the resin, apparently through their RNA component. Examples are given with ribosomes from Escherichia coli, Deinococcus radiodurans, and with clinical isolates of Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA). The ribosomes obtained by this method are unusually intact, so that highly active ribosomes can now be isolated from the clinical isolates, enabling significantly improved in vitro functional assays that will greatly assist the discovery and development of new ribosomally targeted antibiotics. C1 [Maguire, Bruce A.; Contillo, Leonard G.] Groton Labs, Pfizer Global Res & Dev, Dept Exploratory Med Sci, Groton, CT 06340 USA. [Wondrack, Lillian M.] Groton Labs, Pfizer Global Res & Dev, Dept Infect Dis, Groton, CT 06340 USA. [Xu, Zuoyu] NIAID, NIH, Bacteriol & Mycol Branch, Bethesda, MD 20892 USA. RP Maguire, BA (reprint author), Groton Labs, Pfizer Global Res & Dev, Dept Exploratory Med Sci, Groton, CT 06340 USA. EM Bruce.Maguire@pfizer.com; xuzuoyu@niaid.nih.gov NR 19 TC 15 Z9 15 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD JAN PY 2008 VL 14 IS 1 BP 188 EP 195 DI 10.1261/rna.692408 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 242AZ UT WOS:000251698200019 PM 17998293 ER PT J AU Ji, XH AF Ji, Xinhua TI The mechanism of RNase III action: How Dicer dices SO RNA INTERFERENCE SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID DOUBLE-STRANDED-RNA; COLI RIBONUCLEASE-III; ARGONAUTE2 PAZ DOMAIN; ESCHERICHIA-COLI; BINDING DOMAIN; SUBSTRATE-SPECIFICITY; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; DSRNA-BINDING; GENE-EXPRESSION AB Members of the Ribonuclease Ill (RNase 111) family are double-stranded (ds) RNA-specific endoribonucleases, characterized by a signature motif in their active centers and a 2-nucleotide (nt) 3' overhang in their products. Dicer functions as a dsRNA-processing enzyme, producing small interfering RNA (siRNA) of approx. 24 nt in length (approx. 20-basepair RNA duplex with a 2-nt 3' overhang on each end). Bacterial RNase Ill functions not only as a processing enzyme, but also as a binding protein that binds dsRNA without cleaving it. As a processing enzyme it produces siRNA-like RNA of approx. 13 nt in length (approx. 9-basepair duplex with a 2-nt 3' overhang on each end) as well as various types of mature RNA. Dicer is structurally most complicated member of the family; bacterial RNase Ill is comparatively much simpler. One structure is known for Dicer in its RNA-free form (MacRae, Zhou, Li, Repic, Brooks, Cande, Adams, and Doudna, Science 311:195-198); many structures are available for bacterial RNase III, including the first catalytic complex of the entire family (Gan, Tropea, Austin, Court, Waugh, and Ji, Cell 124:355-366). In light of the structural and biochemical information on the RNase III proteins and the structure of a non-Dicer PAZ (Piwi Argonaute Zwille) domain in complex with a 7-basepair RNA duplex with a 2-nt 3' overhang on each end (Ma, Ye, and Patel, Nature 429:318-322), the structure and function of Dicer is being elucidated. C1 NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. RP Ji, XH (reprint author), NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. EM jix@ncifcrf.gov RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU Intramural NIH HHS NR 66 TC 49 Z9 50 U1 0 U2 22 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2008 VL 320 BP 99 EP 116 PG 18 WC Immunology; Microbiology SC Immunology; Microbiology GA BHI61 UT WOS:000253430500005 PM 18268841 ER PT S AU Malecki, M Jedrzejczak, R Puchta, O Stepien, PP Golik, P AF Malecki, Michal Jedrzejczak, Robert Puchta, Olga Stepien, Piotr P. Golik, Pawel BE Maquat, LE Arraiano, CM TI IN VIVO AND IN VITRO APPROACHES FOR STUDYING THE YEAST MITOCHONDRIAL RNA DEGRADOSOME COMPLEX SO RNA TURNOVER IN BACTERIA, ARCHAEA AND ORGANELLES SE Methods in Enzymology LA English DT Review; Book Chapter ID SACCHAROMYCES-CEREVISIAE GENOME; GENE; HELICASE; TRANSCRIPTION; STABILITY; EUKARYOTES; TURNOVER; EXORIBONUCLEASE; RECONSTITUTION; DEGRADATION AB The mitochondrial degradosome (mtEXO) of S. cerevisiae is the main exoribonuclease of yeast mitochondria. It is involved in many pathways of mitochondrial RNA metabolism, including RNA degradation, surveillance, and processing, and its activity is essential for mitochondrial gene function. The mitochondrial degradosome is a very simple example of a 3' to 5'-exoribonucleolytic complex. It is composed of only two subunits: Dss1p, which is an RNR (RNase II-like) family exoribonuclease, and Suv3p, which is a DExH/D-box RNA helicase. The two subunits form a tight complex and their activities are highly interdependent, with the RNase activity greatly enhanced in the presence of the helicase subunit, and the helicase activity entirely dependent on the presence of the ribonuclease subunit. In this chapter, we present methods for studying the function of the yeast mitochondrial degradosome in vivo, through the analysis of degradosome-deficient mutant yeast strains, and in vitro, through heterologous expression in E. coli and purification of the degradosome subunits and reconstitution of a functional complex. We provide the protocols for studying ribonuclease, ATPase, and helicase activities and for measuring the RNA binding capacity of the complex and its subunits. C1 [Malecki, Michal; Puchta, Olga; Stepien, Piotr P.; Golik, Pawel] Warsaw Univ, Dept Genet & Biotechnol, Warsaw, Poland. [Jedrzejczak, Robert] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Puchta Lab, Argonne, IL USA. [Puchta, Olga; Stepien, Piotr P.; Golik, Pawel] PAS, Inst Biochem & Biophys, Warsaw, Poland. RP Malecki, M (reprint author), Warsaw Univ, Dept Genet & Biotechnol, Warsaw, Poland. RI Golik, Pawel/D-7788-2011 OI Golik, Pawel/0000-0001-7814-482X FU Ministry of Science and Higher Education of Poland [2P04A 002 29, 2P04A 054 26, N N301 2380 33]; Faculty of Biology, Warsaw University [BW 1720/46, BW 1680/40]; National Cancer Institute; CoE BioExploratorium project [WKP_1/1.4.3/1/2004/44/44/115/2005] FX This work Was supported by the Ministry of Science and Higher Education of Poland through the Faculty of Biology, Warsaw University Intramural Grants BW#1720/46 and BW#1680/40, by the Intramural Research Program of the National Cancer Institute, the CoE BioExploratorium project: WKP_1/1.4.3/1/2004/44/44/115/2005, and by grants 2P04A 002 29, 2P04A 054 26, and N N301 2380 33 from the Ministry of Science and Higher Education of Poland. We are grateful to Prof. Ewa Bartnik for critical reading of the manuscript. NR 48 TC 7 Z9 9 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374377-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 447 BP 463 EP 488 DI 10.1016/S0076-6879(08)02222-2 PG 26 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIS49 UT WOS:000262438300022 PM 19161856 ER PT S AU Cuthbertson, BJ Blacksheart, PJ AF Cuthbertson, Brandon J. Blacksheart, Perry J. BE Maquat, LE Kiledjian, M TI EVALUATING THE CONTROL OF MRNA DECAY IN FISSION YEAST SO RNA TURNOVER IN EUKARYOTES: ANALYSIS OF SPECIALIZED AND QUALITY CONTROL RNA DECAY PATHWAYS SE Methods in Enzymology LA English DT Review; Book Chapter ID AU-RICH ELEMENT; ZINC-FINGER PROTEINS; FACTOR-ALPHA PRODUCTION; SCHIZOSACCHAROMYCES-POMBE; GENE-EXPRESSION; MAMMALIAN-CELLS; POLYMERASE-II; CONFORMATIONAL-CHANGES; TRANSCRIPTION FACTOR; IRON-DEFICIENCY AB Abnormalities in rates of m RNA decay can lead to changes in steady-state levels of transcripts, which in turn can result in changes in protein production and abnormal phenotypes. For example, mice deficient in the gene encoding tristetraprolin (TTP), a tandem CCCH zinc finger domain protein, develop a complex syndrome that includes wasting, arthritis, and myeloid hyperplasia, all secondary to elevated levels of tumor necrosis factor (TNF). This in turn reflects elevated levels of TNF mRNA, which is a direct "target" of TTP binding and TTP-promoted deadenytation and decay. Three TTP-like proteins are expressed in human and four in mice, all of which bind mRNA and control transcript decay. In contrast, the Schizosoccharomyces pombe genome contains only one TTP-like protein, named Zfs1. Microarray analysis revealed that S. pombe cells deficient in zfs1 overexpress the arz1 mRNA, which has several ideal TTP-like binding sites in its 3'-untranslated region (UTR). We used the "no message in thiamine (nmt)" repressible system, in which thiamine rapidly shuts off gene transcription, to evaluate the relative stability of the arz1 mRNA in wild-type and zfs1-deficient cells. We found that the arz1 mRNA decayed much more rapidly in the presence of endogenous zfs1 than in its absence. The nmt system also proved useful for the study of mRNA sequence elements that are essential for interactions with zfs1, which eventually results in accelerated transcript decay. These studies illustrate the utility of the S. pombe nmt system for evaluating protein-mRNA interactions that affect mRNA decay in vivo and provide an alternative to the use of transcription inhibitors or heat-sensitive polymerase promoters that are used more commonly to evaluate mRNA decay in Saccharomyces cerevesiae. We hope to use this convenient experimental system to unravel the mechanism by which TTP family members, in this and other organisms, bind to mRNAs and promote their instability. C1 [Cuthbertson, Brandon J.; Blacksheart, Perry J.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA. [Blacksheart, Perry J.] Natl Inst Environm Hlth Sci, Clin Res Program, Res Triangle Pk, NC USA. RP Cuthbertson, BJ (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA. FU NIH; NIEHS FX We thank Debbie Stumpo for help with Norhern blots and helpful discussions, Yanhong Liao for help with S. pombe system, and Wi Lai for insightful discussions. We also acknowledge the help of the NIEHS Microarray Core. This work was supported by the Intramural Research Program of the NIH, NIEHS. NR 56 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374584-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 449 BP 73 EP 95 DI 10.1016/S0076-6879(08)02404-X PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIR48 UT WOS:000262253100004 PM 19215754 ER PT J AU Resnik, DB AF Resnik, David B. BE Psillos, S Curd, M TI ETHICS OF SCIENCE SO ROUTLEDGE COMPANION TO PHILOSOPHY OF SCIENCE SE Routledge Philosophy Companion LA English DT Article; Book Chapter C1 NIEHS, NIH, Bethesda, MD 20892 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-00050-2 J9 ROUTL PHILOS COMPAN PY 2008 BP 149 EP 158 PG 10 WC History & Philosophy Of Science; Philosophy SC History & Philosophy of Science; Philosophy GA BMZ54 UT WOS:000273989500015 ER PT J AU Sitzmann, M Filippov, IV Nicklaus, MC AF Sitzmann, M. Filippov, I. V. Nicklaus, M. C. TI Internet resources integrating many small-molecule databases SO SAR AND QSAR IN ENVIRONMENTAL RESEARCH LA English DT Article; Proceedings Paper CT Conference on Computational Methods in Toxicology and Pharmacology Integrating Internet Resources CY SEP 01-05, 2007 CL Moscow, RUSSIA DE databases; small molecule databases; Chemical Structure Lookup Service; structure identifiers AB New data, tools and services recently made available on the web server (http://cactus.nci.nih.gov) of the Computer-Aided Drug Design (CADD) Group, NCI, NIH, developed in the context of chemoinformatics and drug development work, are presented. These tools are designed for searching for structures in very large databases of small molecules. One of them is a web service-the Chemical Structure Lookup Service (CSLS)-for very rapid structure lookup in an aggregated collection of more than 80 databases comprising more than 27 million unique structures at the time of this writing. CSLS contains pointers to the entries in toxicology-related databases, catalogues of commercially available samples, drugs, assay results data sets, and databases in several other categories. CSLS allows the user to find out very rapidly in which one(s) of all these databases a given structure occurs independent of the representation of the input structure, by making use of InChIs as well as new CACTVS hashcode-based identifiers. These latter, calculable, identifiers are designed to take into account tautomerism, different resonance structures drawn for charged species, and presence of additional fragments. They make possible fine-tunable yet rapid compound identification and database overlap analyses in very large compound collections. C1 [Sitzmann, M.; Nicklaus, M. C.] NCI, Comp Aided Drug Design Grp, Med Chem Lab, Ctr Canc Res,NIH,DHHS, Frederick, MD 21701 USA. [Filippov, I. V.] NCI Frederick SAIC, Comp Aided Drug Design Grp, Med Chem Lab, Frederick, MD USA. RP Nicklaus, MC (reprint author), NCI, Comp Aided Drug Design Grp, Med Chem Lab, Ctr Canc Res,NIH,DHHS, Frederick, MD 21701 USA. EM mn1@helix.nih.gov RI Nicklaus, Marc/N-4183-2014; OI Nicklaus, Marc/0000-0002-4775-7030 FU NCI NIH HHS [N01-CO-12400] NR 11 TC 26 Z9 26 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1062-936X J9 SAR QSAR ENVIRON RES JI SAR QSAR Environ. Res. PY 2008 VL 19 IS 1-2 BP 1 EP 9 DI 10.1080/10629360701843540 PG 9 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications; Environmental Sciences; Mathematical & Computational Biology; Toxicology SC Chemistry; Computer Science; Environmental Sciences & Ecology; Mathematical & Computational Biology; Toxicology GA 269PC UT WOS:000253660300001 PM 18311630 ER PT S AU Goldfarb, LG Olive, M Vicart, P Goebel, HH AF Goldfarb, Lev G. Olive, Montse Vicart, Patrick Goebel, Hans H. BE Laing, NG TI Intermediate Filament Diseases: Desminopathy SO SARCOMERE AND SKELETAL MUSCLE DISEASE SE Advances in Experimental Medicine and Biology LA English DT Article ID ALPHA-B-CRYSTALLIN; DOMINANT MYOFIBRILLAR MYOPATHY; POSTERIOR POLAR CATARACT; HELICAL COILED COILS; MICE LACKING DESMIN; SKELETAL MYOPATHY; DILATED CARDIOMYOPATHY; ELECTRON-MICROSCOPY; MUSCULAR-DYSTROPHY; MISSENSE MUTATIONS AB Desminopathy is one of the most common intermediate filament human disorders associated with mutations in closely interacting proteins, desmin and alphaB-crystallin. The inheritance pattern in familial desminopathy is characterized as autosomal dominant or autosomal recessive, but many cases have no family history. At least some and likely most sporadic desminopathy cases arc associated with de novo DES mutations. The age of disease onset and rate of progression may vary depending on the type of inheritance and location of the causative mutation. Typically, the illness presents with lower and later upper limb muscle weakness slowly spreading to involve truncal, neck-flexor, facial and bulbar muscles. Skeletal myopathy is often combined with cardiomyopathy manifested by conduction blocks, arrhythmias and chronic heart failure resulting in premature sudden death. Respiratory muscle weakness is a major complication in some patients. Sections of the affected skeletal and cardiac muscles show abnormal fibre areas containing chimeric aggregates consisting of desmin and other cytoskeletal proteins. Various DES gene mutations: point mutations, an insertion, small in-frame deletions and a larger exon-skipping deletion, have been identified in desminopathy patients. The majority of these mutations are located in conserved alpha-helical segments, but additional mutations have recently been identified in the tail domain. Filament and network assembly studies indicate that most but not an disease-causing mutations make desmin assembly-incompetent and able to disrupt a pre-existing filamentous network in dominant-negative fashion. AlphaB-crystallin serves as a chaperone for desmin preventing its aggregation under various forms of stress; mutant CRYAB causes cardiac and skeletal myopathies identical to those resulting from DES mutations. C1 [Goldfarb, Lev G.] NIH, Bethesda, MD 20892 USA. RP Goldfarb, LG (reprint author), NIH, 5625 Fishers Lane,Room 4S06, Bethesda, MD 20892 USA. EM goldfarbl@ninds.nih.gov OI Olive, Montse/0000-0001-5727-0165 FU National Institute of Neurological Disorders and Stroke; National Institutes of Health, USA; FIS [PI051213]; Association Francaise contre les Myopathics (AFM); Universite Paris Diderot FX This work was supported in part by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, USA (LGG). MO was supported by a grant PI051213 from FIS. PV team was supported by the Association Francaise contre les Myopathics (AFM) and the Universite Paris Diderot. NR 117 TC 48 Z9 54 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-84846-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2008 VL 642 BP 131 EP 164 PG 34 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BIP66 UT WOS:000261700300012 PM 19181099 ER PT J AU Narva, AS AF Narva, Andrew S. TI The National Kidney Disease Education Program and other related efforts in the United States SO SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION LA English DT Article; Proceedings Paper CT 11th Bergmeyer Conference on Markers of Kidney Diseases CY MAR 03-05, 2008 CL Grainau, GERMANY DE albumin; chronic kidney disease; creatinine; estimated glomerular filtration rate AB The National Kidney Disease Education Program (NKDEP) works to reduce the morbidity and mortality caused by chronic kidney disease (CKD) and its complications through educational efforts targeted towards at-risk communities, patients and health-care professionals. NKDEP aims to improve early detection of CKD, facilitate identification of patients at greatest risk for progression to kidney failure and promote evidence-based interventions. Barriers to achieving these goals include confusion and misunderstanding of the laboratory tests used to identify and monitor patients with CKD. Through the Laboratory Working Group, NKDEP has collaborated with the clinical chemistry community to standardize creatinine measurements, promote the routine reporting of eGFR and standardize the measurement and reporting of urine albumin. It is hoped that these efforts will improve screening, clinical care and research in CKD and facilitate the implementation of evidence-based care recommended by the National Kidney Foundation and others. C1 [Narva, Andrew S.] NIDDK, Bethesda, MD USA. RP Narva, AS (reprint author), 2 Democracy Plaza,Room 645,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA. EM narvaa@niddk.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0036-5513 J9 SCAND J CLIN LAB INV JI Scand. J. Clin. Lab. Invest. PY 2008 VL 68 SU 241 BP 12 EP 15 DI 10.1080/00365510802144870 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 312PG UT WOS:000256682700003 ER PT J AU Gao, Y Linet, MS Gridley, G Mellemkjaer, L Hemminki, K Goldin, LR Landgren, O AF Gao, Ying Linet, Martha S. Gridley, Gloria Mellemkjaer, Lene Hemminki, Kari Goldin, Lynn R. Landgren, Ola TI Shared susceptibility for celiac disease and inflammatory bowel disease? SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter C1 [Gao, Ying] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Mellemkjaer, Lene] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Hemminki, Kari] Ctr Family & Community Med, Div Mol Genet Epidemiol, Heidelberg, Germany. RP Gao, Y (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Bldg EPS,Room 7016, Bethesda, MD 20892 USA. EM gaoying@mail.nih.gov FU Intramural NIH HHS [Z01 CP004410-31] NR 5 TC 1 Z9 1 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 2008 VL 43 IS 10 BP 1279 EP 1280 DI 10.1080/00365520802158630 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 349YC UT WOS:000259318200017 PM 18609125 ER PT J AU Ramos, HL Valencia-Pacheco, G Alcocer-Varela, J AF Ramos, H. L. Valencia-Pacheco, G. Alcocer-Varela, J. TI Constitutive STAT3 activation in peripheral CD3(+) cells from patients with primary Sjogren's syndrome SO SCANDINAVIAN JOURNAL OF RHEUMATOLOGY LA English DT Article ID T-CELLS; RHEUMATOID-ARTHRITIS; GENE-EXPRESSION; SALIVARY-GLANDS; IN-VIVO; INTERLEUKIN-10; DISEASE; FAMILY; IL-10; CYTOKINES AB Objective: Signal transducers and activators of transcription (STATs) are crucial mediators of cytokine signalling. Constitutive activation of STATs, especially STAT3, has been reported in several diseases. Primary Sjgren's syndrome (pSS) is associated with overproduction of cytokines such as interleukin-10 (IL-10), although the mechanism by which this occurs is unknown. As STAT3 is a potent inducer of IL-10, this study focused on determining the pattern of STAT3 activation in peripheral lymphocytes from patients with pSS. Methods: Twelve pSS patients and 12 healthy age-matched control subjects were studied. Peripheral blood mononuclear cells (PBMCs) were isolated by gradient centrifugation. Phosphorylated STAT3 (pSTAT3) and also STAT3 expression were determined by flow cytometry in gated CD3(+) and CD19(+) lymphocytes. Similarly, pJak1 and pTyk2 were also determined in gated CD3(+) lymphocytes. Results: Although the protein expression of STAT3 was similar among controls and pSS patients, we found that STAT3 was constitutively activated in CD3+ lymphocytes from pSS patients. Neither Jak1 nor Tyk2 (the upstream activators of STAT3) was activated in pSS CD3(+) lymphocytes, suggesting that the constitutive activation of STAT3 observed in pSS patients might not depend on cytokine stimulation but instead might be the result of an abnormal inactivation of pSTAT3. Conclusions: These data provide evidence of abnormal STAT3 signalling in T cells from pSS patients. C1 [Ramos, H. L.; Alcocer-Varela, J.] Natl Inst Med Sci & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico. RP Ramos, HL (reprint author), NIH, NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. EM ramosh@mail.nih.gov; jalcocer@quetzal.innsz.mx NR 31 TC 13 Z9 13 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0300-9742 J9 SCAND J RHEUMATOL JI Scand. J. Rheumatol. PY 2008 VL 37 IS 1 BP 35 EP 39 DI 10.1080/03009740701606010 PG 5 WC Rheumatology SC Rheumatology GA 251FK UT WOS:000252356900007 PM 18189193 ER PT J AU Gogtay, N AF Gogtay, Nitin TI Cortical brain development in schizophrenia: Insights from neuroimaging studies in childhood-onset schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE childhood-onset schizophrenia; structural brain imaging ID 1ST EPISODE SCHIZOPHRENIA; GRAY-MATTER LOSS; 1ST-EPISODE SCHIZOPHRENIA; NONPSYCHOTIC CHILDREN; SPECTRUM DISORDER; HEALTHY SIBLINGS; CEREBRAL-CORTEX; VOLUME CHANGES; ABNORMALITIES; HALLUCINATIONS AB Childhood-onset schizophrenia (COS; defined as onset by age 12 years) is rare, difficult to diagnose, and represents a severe and chronic phenotype of the adult-onset illness. A study of childhood-onset psychoses has been ongoing at the National Institute of Mental Health (NIMH) since 1990, where children with COS and severe atypical psychoses (provisionally labeled "multidimensionally impaired" or MDI by the NIMH team) are studied prospectively along with all first-degree relatives. COS subjects have robust cortical gray matter (GM) loss during adolescence, which appears to be an exaggeration of the normal cortical GM developmental pattern and eventually mimics the pattern seen in adult-onset cases as the children become young adults. These cortical GM changes in COS are diagnostically specific and seemingly unrelated to the effects of medications. Furthermore, the cortical GM loss is also shared by healthy full siblings of COS pro-bands suggesting a genetic influence on the abnormal brain development. C1 NIMH, NIH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Gogtay, N (reprint author), NIMH, NIH, Child Psychiat Branch, Bldg 10,Room 3N202,10 Ctr Dr, Bethesda, MD 20892 USA. EM gogtayn@mail.nih.gov RI Gogtay, Nitin/A-3035-2008 FU Intramural NIH HHS NR 82 TC 58 Z9 58 U1 6 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2008 VL 34 IS 1 BP 30 EP 36 DI 10.1093/schbul/sbm103 PG 7 WC Psychiatry SC Psychiatry GA 248JE UT WOS:000252148800008 PM 17906336 ER PT J AU McClure, RK Carew, K Greeter, S Maushauer, E Steen, G Weinberger, DR AF McClure, Robert K. Carew, Khary Greeter, Stacy Maushauer, Emily Steen, Grant Weinberger, Daniel R. TI Absence of regional brain volume change in schizophrenia associated with short-term atypical antipsychotic treatment SO SCHIZOPHRENIA RESEARCH LA English DT Article DE treatment naive; first episode; chronic schizophrenia; caudate; atypical antipsychotic; ITK-SNAP; voxel-based morphometry; VBM ID EARLY-ONSET SCHIZOPHRENIA; VOXEL-BASED MORPHOMETRY; CAUDATE NUCLEI VOLUMES; BASAL GANGLIA VOLUMES; GRAY-MATTER LOSS; 1ST EPISODE; TYPICAL ANTIPSYCHOTICS; PSYCHOTIC-PATIENTS; WHITE-MATTER; GREY-MATTER AB The first aim of this pilot study was to determine if longitudinal change in caudate volume could be detected in chronic schizophrenic patients after 12 weeks of atypical antipsychotic treatment. A sub-aim of the first aim was to determine if similar results could be obtained from an operator-assisted segmentation tool for volumetric imaging (ITK-SNAP) and voxel-based morphometry (VBM) methods in the caudate. The second aim was to determine if frontal and temporal lobe grey matter, white matter, ventricular and sulcal cerebrospinal fluid volume change could be detected after 12 weeks of atypical antipsychotic treatment with VBM. Ten chronic schizophrenic inpatients, with illness duration averaging 10.6 years, underwent two MRI scans. The first scan was obtained after a mean of 39.4 days of antipsychotic withdrawal. The second MRI was obtained following twelve weeks of atypical antipsychotic treatment. Caudate volume change was first measured with ITK-SNAP. Then the location of grey matter volume change in the caudate was identified with VBM. Finally, the location of frontal and temporal lobe grey matter, white matter, ventricular and sulcal cerebrospinal fluid volume changes were identified with VBM. No longitudinal change in caudate volume or grey matter volume was observed after brief periods of atypical antipsychotic treatment. ITK-SNAP and VBM methods showed very similar results in the caudate. No statistically significant change was identified in the volume of frontal or temporal lobe grey matter, white matter, and lateral, third, or fourth ventricular cerebrospinal fluid. Although the results do not directly show that brief periods of atypical antipsychotic treatment are associated with basal ganglia and cortical volume change, there is much evidence to suggest that such an association exists. (C) 2007 Published by Elsevier B.V. C1 [McClure, Robert K.; Carew, Khary; Greeter, Stacy; Maushauer, Emily; Steen, Grant] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27510 USA. [Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP McClure, RK (reprint author), Univ N Carolina, Dept Psychiat, CB 7160,Room 247,Wing C, Chapel Hill, NC 27510 USA. EM robert_mcclure@med.unc.edu NR 61 TC 25 Z9 25 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2008 VL 98 IS 1-3 BP 29 EP 39 DI 10.1016/j.schres.2007.05.012 PG 11 WC Psychiatry SC Psychiatry GA 253BQ UT WOS:000252494100004 PM 17976957 ER PT J AU Weickert, CS Rothmond, DA Hyde, TA Kleinman, JE Straub, RE AF Weickert, Cynthia Shannon Rothmond, Debora A. Hyde, Thomas A. Kleinman, Joel E. Straub, Richard E. TI Reduced DTNBP1 (dysbindin-1) mRNA in the hippocampal formation of schizophrenia patients SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; postmortem; hippocampus; spinophilin; synaptophysin; candidate gene; synapse; synaptic pathology ID GENETIC-VARIATION; 6P22.3 GENE; HUMAN BRAIN; EXPRESSION; SYNAPTOPHYSIN; CORTEX AB Genetic and molecular studies indicate that dysbindin-1 plays a role in the pathophysiology of schizophrenia. We examined dysbindin-1 mRNA in the hippocampal formation of patients with schizophrenia and found reduced expression in dentate granule and polymorph cells and in hippocampal field CA3, but not in CA1. Furthermore, there were positive correlations between dysbindin-1 mRNA and expression of synaptic markers known to be reduced in schizophrenia. Our results indicate that previously reported dysbindin-1 protein reductions may be due in part to decreased dysbindin-1 mRNA and that reduced dysbindin-1 may contribute to hippocampal formation synaptic pathology in schizophrenia. (C) 2007 Elsevier B.V. All rights reserved. C1 [Weickert, Cynthia Shannon] Univ New S Wales, Prince Wales Med Res Inst, Schizophrenia Res Inst, Dept Psychiat, Randwick, NSW 2031, Australia. [Weickert, Cynthia Shannon; Rothmond, Debora A.] NIMH, MiNDS Unit, Clin Brain Disorders Branch, IRP,NIH, Bethesda, MD 20892 USA. [Hyde, Thomas A.; Kleinman, Joel E.] NIMH, Neuropathol Sect, Clin Brain Disorders Branch, IRP,NIH, Bethesda, MD 20892 USA. [Straub, Richard E.] NIMH, Genes Cognit & Psychosis Program, IRP, NIH, Bethesda, MD 20892 USA. RP Weickert, CS (reprint author), Univ New S Wales, Prince Wales Med Res Inst, Schizophrenia Res Inst, Dept Psychiat, Barker St, Randwick, NSW 2031, Australia. EM c.shannonweickert@unsw.edu.au RI Shannon Weickert, Cynthia/G-3171-2011 FU Intramural NIH HHS [NIH0011264699]; PHS HHS [NIH0011264699] NR 17 TC 76 Z9 78 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2008 VL 98 IS 1-3 BP 105 EP 110 DI 10.1016/j.schres.2007.05.041 PG 6 WC Psychiatry SC Psychiatry GA 253BQ UT WOS:000252494100013 PM 17961984 ER PT J AU Mitkus, SN Hyde, TM Vakkalanka, R Kolachana, B Weinberger, DR Kleinman, JE Lipska, BK AF Mitkus, Shruti N. Hyde, Thomas M. Vakkalanka, Radhakrishna Kolachana, Bhaskar Weinberger, Daniel R. Kleinman, Joel E. Lipska, Barbara K. TI Expression of oligodendrocyte-associated genes in dorsolateral prefrontal cortex of patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; myelin; oligodendrocytes; MOBP; CNP; OLIG2; postmortem studies ID 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; ANTERIOR CINGULATE CORTEX; MYELINATION-RELATED GENES; FAMILY-BASED ASSOCIATION; BIPOLAR DISORDER; MESSENGER-RNA; JAPANESE POPULATION; CONVERGENT EVIDENCE; PROTEIN EXPRESSION; CHINESE POPULATION AB Prior studies have found decreased mRNA expression of oligodendrocyte-associated genes in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia. However, it is unclear which specific genes are affected and whether the changes occur in the cortical white or grey matter. We assessed the mRNA expression levels of four oligodendrocyte-related genes: myelin-associated basic protein (MOBP), myelin-associated glycoprotein (MAG), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and oligodendrocyte-lineage transcription factor 2 (OLIG2) in DLPFC white and grey matter using quantitative-PCR (similar to 70 controls and similar to 30 patients with schizophrenia). We also examined the effects of high-risk polymorphisms in CNP and OLIG2 on mRNA levels of these genes. We found that genetic polymorphisms in CNP (rs2070106) and OLIG2 (rs1059004 and rs9653711), previously associated with schizophrenia, predicted low expression of these genes. Expression of MAG, CNP and OLIG2 did not differ between patients with schizophrenia and controls in the grey or white matter but MOBP mRNA levels were increased in the DLPFC white matter in patients with a history of substance abuse. MOBP and CNP protein in the white matter was not altered. Although previously reported reductions in the expression of myelin-related genes in the DLPFC were not detected, we show that individuals carrying risk-associated alleles in oligodendrocyte-related genes had relatively lower transcript levels. These data illustrate the importance of genetic background in gene expression studies in schizophrenia. Published by Elsevier B.V. C1 [Mitkus, Shruti N.; Hyde, Thomas M.; Vakkalanka, Radhakrishna; Kolachana, Bhaskar; Weinberger, Daniel R.; Kleinman, Joel E.; Lipska, Barbara K.] NIMH, Clin Brain Disorders Branch, Sect Neuropathol, DIRP,NIH, Bethesda, MD 20892 USA. RP Lipska, BK (reprint author), 10 Ctr Dr,Room 4N306, Bethesda, MD 20892 USA. EM lipskab@intra.nimh.nih.gov FU Intramural NIH HHS [Z01 MH002399-18, Z99 MH999999] NR 38 TC 50 Z9 50 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2008 VL 98 IS 1-3 BP 129 EP 138 DI 10.1016/j.schres.2007.09-032 PG 10 WC Psychiatry SC Psychiatry GA 253BQ UT WOS:000252494100016 PM 17964117 ER PT J AU Sharma, A AF Sharma, Ajay TI Manna from Hell SO SCIENTIST LA English DT Letter C1 NICHHD, Bethesda, MD 20892 USA. RP Sharma, A (reprint author), NICHHD, Bethesda, MD 20892 USA. EM sharmaa@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD JAN PY 2008 VL 22 IS 1 BP 16 EP 16 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 248GO UT WOS:000252140900003 ER PT J AU Vydelingum, NA AF Vydelingum, Nadarajen A. TI Bringing order to authorship SO SCIENTIST LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Vydelingum, NA (reprint author), NCI, Bethesda, MD 20892 USA. EM vydelinn@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD JAN PY 2008 VL 22 IS 1 BP 17 EP 17 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 248GO UT WOS:000252140900010 ER PT J AU Sloand, EM AF Sloand, Elaine M. TI Myelodysplastic syndromes: Introduction SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material ID CELL TRANSPLANTATION; LEUKEMIA C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Sloand, EM (reprint author), NHLBI, Hematol Branch, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HL999999] NR 12 TC 4 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2008 VL 45 IS 1 BP 1 EP 2 DI 10.1053/j.seminhmatol.2007.11.008 PG 2 WC Hematology SC Hematology GA 250UM UT WOS:000252326600001 PM 18179962 ER PT J AU Sloand, EM Rezvani, K AF Sloand, Elaine M. Rezvani, Katayoun TI The role of the immune system in myelodysplasia: Implications for therapy SO SEMINARS IN HEMATOLOGY LA English DT Review ID WILMS-TUMOR GENE; CYTOTOXIC T-LYMPHOCYTES; ACUTE MYELOID-LEUKEMIA; MINIMAL RESIDUAL DISEASE; BONE-MARROW-CELLS; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; CHRONIC MYELOGENOUS LEUKEMIA; X-CHROMOSOME INACTIVATION; ANTI-THYMOCYTE-GLOBULIN; CYCLOSPORINE-A THERAPY AB Patients with myelodysplastic syndrome (MDS) have intrinsic, usually acquired genetic defects in their hematopoietic stem cells, but some others exhibit T-cell-mediated inhibition of hematopoiesis and good responses to immunosuppression. In these cases, MDS shares a similar pathophysiology with aplastic anemia (AA). Here, we review the evidence supporting a role of the immune system in the pathophysiology of MDS and the results of clinical trials of immunosuppressive agents. C1 [Sloand, Elaine M.; Rezvani, Katayoun] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Sloand, EM (reprint author), NHLBI, Hematol Branch, Bldg 10 CRC,4E Room 5230, Bethesda, MD 20892 USA. EM sloande@nih.gov NR 115 TC 39 Z9 41 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2008 VL 45 IS 1 BP 39 EP 48 DI 10.1053/j.seminhematol.2007.11.006 PG 10 WC Hematology SC Hematology GA 250UM UT WOS:000252326600007 PM 18179968 ER PT J AU Barrett, AJ Savani, BN AF Barrett, A. John Savani, Bipin N. TI Allogeneic stem cell transplantation for myelodysplastic syndrome SO SEMINARS IN HEMATOLOGY LA English DT Article ID ACUTE-MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; CORD BLOOD TRANSPLANTATION; VERSUS-HOST-DISEASE; INTENSITY CONDITIONING REGIMENS; IDENTICAL SIBLING DONORS; PROGNOSTIC-FACTORS; MULTILINEAGE DYSPLASIA; LONG-TERM AB Although it is only used to treat a minority of patients with myelodysplastic syndromes, stem cell transplantation (SCT) is the only proven curative treatment for this condition. Because MDS occurs in a population of older adults with significant comorbidities, reduced-intensity conditioning (RIC) regimens have been particularly important in extending safe SCT to the large MDS population over the age of 60 years. Extension of the unrelated donor pool together with the introduction of umbilical cord blood transplants in adults has extended the number of patients with suitable donors. Nevertheless overall mortality from SCT is greater than 50% because of relapse and non-relapse mortality (NRM). New developments to improve outcome include the tailoring of the transplant approach to the individual based on age and comorbidity, and the use of pretransplant chemotherapy to reduce disease bulk prior to transplant, as well as the introduction of post-transplant immunotherapy (pre-emptive donor lymphocyte infusions) and chemotherapy to prevent relapse. Further improvements in transplant outcome await better ways to reconstitute immunity and amplify the graft-versus-leukemia (GVL) effect without causing graft-versus-host disease (GVHD), as well as further extension of the donor pool and exploration of risk-adapted regimens for the population of MDS in their seventh to eighth decade. C1 [Barrett, A. John] NHLBI, NIH, Hematol Branch, Stem Cell Allogenet Transplantat Sect, Bethesda, MD 20892 USA. [Savani, Bipin N.] Vanderbilt Univ Transplant Program, Nashville, TN USA. [Savani, Bipin N.] Vet Affairs Med Ctr, Nashville, TN 37212 USA. RP Barrett, AJ (reprint author), NHLBI, NIH, Hematol Branch, Stem Cell Allogenet Transplantat Sect, Bldg 10,Hatfield CRC,Room 3-5330,10 Ctr Dr,MSC 12, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov NR 79 TC 22 Z9 25 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2008 VL 45 IS 1 BP 49 EP 59 DI 10.1053/j.seminhematol.2007.1.0.005 PG 11 WC Hematology SC Hematology GA 250UM UT WOS:000252326600008 PM 18179969 ER PT S AU Rothman, RB Blough, BE Baumann, MH AF Rothman, Richard B. Blough, Bruce E. Baumann, Michael H. BE DiGiovanni, G DiMatteo, V Esposito, E TI Dopamine/serotonin releasers as medications for stimulant addictions SO SEROTONIN-DOPAMINE INTERACTION: EXPERIMENTAL EVIDENCE AND THERAPEUTIC RELEVANCE SE Progress in Brain Research LA English DT Review; Book Chapter DE alcohol; amphetamine; cocaine; dopamine; serotonin; treatment; transporter ID PRIMARY PULMONARY-HYPERTENSION; VALVULAR HEART-DISEASE; CENTRAL-NERVOUS-SYSTEM; SMOOTH-MUSCLE-CELLS; SEROTONIN TRANSPORTER INHIBITORS; PROGRESSIVE-RATIO SCHEDULE; INDUCED LOCOMOTOR-ACTIVITY; COCAINE-SEEKING BEHAVIOR; D-AMPHETAMINE TREATMENT; VENTRAL TEGMENTAL AREA AB The use of 'agonist therapy' for cocaine and methamphetamine addiction involves administration of stimulant-like medications (e. g. monoamine releasers) to reduce withdrawal symptoms and prevent relapse. A significant problem with this strategy is that many candidate medications possess abuse liability due to activation of mesolimbic dopamine (DA) neurons in the brain. One way to reduce DA-mediated abuse liability of candidate drugs might be to add in serotonin (5-HT)-releasing properties, since substantial evidence shows that 5-HT neurons provide an inhibitory influence over mesolimbic DA neurons. This chapter addresses several key issues related to the development of dual DA/5-HT releasers for the treatment of substance use disorders. First, we briefly summarize the evidence supporting a dual deficit in DA and 5-HT function during withdrawal from chronic cocaine or alcohol abuse. Second, we discuss data demonstrating that 5-HT release can dampen DA-mediated stimulant effects, and the 'anti-stimulant' role of 5-HT(2C) receptors is considered. Next, the mechanisms underlying potential adverse effects of 5-HT releasers are described. Finally, we discuss recently published data with PAL-287, a novel non-amphetamine DA/5-HT-releasing agent that suppresses cocaine self-administration but lacks positive reinforcing properties. It is concluded that DA/5-HT releasers could be useful therapeutic adjuncts for the treatment of cocaine and alcohol addictions as well as for obesity, attention deficit disorder and depression. C1 [Rothman, Richard B.; Baumann, Michael H.] Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD USA. [Blough, Bruce E.] Res Triangle Inst Int, Chem & Life Sci Grp, Res Triangle Pk, NC USA. RP Rothman, RB (reprint author), Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD USA. EM rrothman@mail.nih.gov FU Intramural NIH HHS; NIDA NIH HHS [R01 DA12970] NR 173 TC 28 Z9 28 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53235-0 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2008 VL 172 BP 385 EP 406 DI 10.1016/S0079-6123(08)00919-9 PG 22 WC Neurosciences SC Neurosciences & Neurology GA BQB94 UT WOS:000280603200020 PM 18772043 ER PT S AU Hempel, LU Kalamegham, R Smith, JE Oliver, B AF Hempel, Leonie U. Kalamegham, Rasika Smith, John E., III Oliver, Brian BE VanDoren, M TI DROSOPHILA GERMLINE SEX DETERMINATION: INTEGRATION OF GERMLINE AUTONOMOUS CUES AND SOMATIC SIGNALS SO SEX DETERMINATION AND SEXUAL DEVELOPMENT SE CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY LA English DT Review ID BAG-OF-MARBLES; OVARIAN-TUMOR GENE; CELL SELF-RENEWAL; MELANOGASTER MEIGEN DIPTERA; ALTERNATIVE SPLICE-SITE; GAP-JUNCTION PROTEINS; EGG CHAMBER FORMATION; LINE STEM-CELLS; FEMALE GERMLINE; PRIMARY TRANSCRIPT AB The Drosophila testis and ovary are major genetically tractable systems for studying stem cells and their regulation. This has resulted in a deep understanding of germline stem cell regulation by the microenvironment, or niche. The male and female germline niches differ. Since sex is determined through different mechanisms in the soma than in the germline, genetic or physical manipulations can be used to experimentally mismatch somatic and germline sexual identities. The phenotypic consequences of these mismatches have striking similarities to those resulting from manipulations of signals within the niche. A critical role of the germline sex determination pathway may therefore be to ensure the proper receipt and processing of signals from the niche. C1 [Hempel, Leonie U.; Kalamegham, Rasika; Smith, John E., III; Oliver, Brian] NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hempel, LU (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, 50 S Dr, Bethesda, MD 20892 USA. RI Smith, John/I-9077-2012 OI Smith, John/0000-0002-0888-1274 FU NIH; NIDDK FX We thank members of the Oliver lab, Mary Lilly, Elissa Lei, and jur-rien Dean for helpful comments. This research was supported by the Intramural Research Program of the NIH, NIDDK. NR 133 TC 9 Z9 10 U1 1 U2 8 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 978-0-12-374496-8 J9 CURR TOP DEV BIOL PY 2008 VL 83 BP 109 EP + DI 10.1016/S0070-2153(08)00404-3 PG 44 WC Developmental Biology SC Developmental Biology GA BIP74 UT WOS:000261716300004 PM 19118665 ER PT J AU Singh, AP Castranio, T Scott, G Guo, D Harris, MA Ray, M Harris, SE Mishina, Y AF Singh, A. P. Castranio, T. Scott, G. Guo, D. Harris, M. A. Ray, M. Harris, S. E. Mishina, Y. TI Influences of reduced expression of maternal bone morphogenetic protein 2 on mouse embryonic development SO SEXUAL DEVELOPMENT LA English DT Article DE BMP2; decidualization; hypomorphic; neural tube closure; omphalocele ID NEURAL CREST; WALL DEFECTS; BMP2; NEURULATION; MICE; RNA; DECIDUALIZATION; DEFICIENT; CLOSURE; CELLS AB Bone morphogenetic protein 2 (BMP2) was originally found by its osteoinductive ability, and recent genetic analyses have revealed that it plays critical roles during early embryogenesis, cardiogenesis, decidualization as well as skeletogenesis. In the course of evaluation of the conditional allele for Bmp2, we found that the presence of a neo cassette, a selection marker needed for gene targeting events in embryonic stem cells, in the 3' untranslated region of exon 3 of Bmp2, reduced the expression levels of Bmp2 both in embryonic and maternal mouse tissues. Some of the embryos that were genotyped as transheterozygous for the floxed allele with the neo cassette over the conventional null allele (fn/-) showed a lethal phenotype including defects in cephalic neural tube closure and ventral abdominal wall closure. The number of embryos exhibiting these abnormalities was increased when, due to different genotypes, expression levels of Bmp2 in maternal tissues were lower. These results suggest that the expression levels of Bmp2 in both embryonic and maternal tissues influence the normal neural tube closure and body wall closure with different thresholds. Copyright (C) 2008 S. Karger AG, Basel. C1 [Singh, A. P.; Castranio, T.; Mishina, Y.] Natl Inst Environm Hlth Sci, Mol Dev Biol Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. [Scott, G.; Ray, M.; Mishina, Y.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. [Harris, M. A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Mishina, Y (reprint author), Natl Inst Environm Hlth Sci, Mol Dev Biol Grp, Lab Reprod & Dev Toxicol, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM mishina@niehs.nih.gov RI Singh, Ajeet/G-3935-2013 FU NIEHS/NIH [ES071003-10] FX We gratefully thank Drs. Hongbing Zhang and Allan Bradley for Bmp2 conventional null mice. We thank Ms. Leigh E. Davis, Ijeoma Nwosu, Gloria MacDonald, and Kelly McCann for their technical support, Ms. Tonya Miller for her excellent service of maintenance of the mouse colonies. This work was supported by the Intramural Research Program of the NIEHS/NIH to Y.M. (ES071003-10). NR 25 TC 17 Z9 17 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-5425 J9 SEX DEV JI Sex. Dev. PY 2008 VL 2 IS 3 BP 134 EP 141 DI 10.1159/000143431 PG 8 WC Developmental Biology SC Developmental Biology GA 345GM UT WOS:000258984300003 PM 18769073 ER PT J AU Hobbs, MM van der Pol, B Totten, P Gaydos, CA Wald, A Warren, T Winer, RL Cook, RL Deal, CD Rogers, ME Schachter, J Holmes, KK Martin, DH AF Hobbs, Marcia M. van der Pol, Barbara Totten, Patricia Gaydos, Charlotte A. Wald, Anna Warren, Terri Winer, Rachel L. Cook, Robert L. Deal, Carolyn D. Rogers, M. Elizabeth Schachter, Julius Holmes, King K. Martin, David H. TI From the NIH: Proceedings of a workshop on the importance of self-obtained vaginal specimens for detection of sexually transmitted infections SO SEXUALLY TRANSMITTED DISEASES LA English DT Article; Proceedings Paper CT Workshop on the Importance of Self-Obtained Vaginal Specimens for Detection of Sexually Transmitted Infections CY JUN 27, 2006 CL Bethesda, MD SP NIH ID LIGASE CHAIN-REACTION; HERPES-SIMPLEX-VIRUS; TRANSCRIPTION-MEDIATED AMPLIFICATION; NEISSERIA-GONORRHOEAE INFECTIONS; CHLAMYDIA-TRACHOMATIS INFECTIONS; HUMAN-PAPILLOMAVIRUS INFECTION; COLLECTED CERVICAL SAMPLES; RECURRENT GENITAL HERPES; FEMALE SEX WORKERS; PAPUA-NEW-GUINEA AB On June 27, 2006, the NIH conducted a workshop to review published data and current field practices supporting the use of self-obtained vaginal swabs (SOVs) as specimens for diagnosis of sexually transmitted infections (STIs). The workshop also explored the design of studies that could support FDA clearance of SOVs for STI testing, particularly for specimens collected in nonclinical settings including patients' homes. This report summarizes the workshop findings and recommendations. Participants concluded that self-obtained vaginal swabs are well accepted by women of all ages and that SOVs perform as well as or better than other specimen types for Chlamydia trachomatis and Neisseria gonorrhoeae detection using transcription-mediated amplification. In addition, workshop participants recommended the validation of SOV testing by public health practitioners and manufacturers of STI diagnostic tests to expedite incorporation of SOVs as a diagnostic option in clinical and nonclinical settings for Chlamydia trachomatis and Neisseria gonorrhoeae testing. Similarly, SOVs should be explored for use in the diagnosis of other sexually transmitted pathogens. C1 [Hobbs, Marcia M.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA. [van der Pol, Barbara] Indiana Univ, Indianapolis, IN 46204 USA. [Totten, Patricia; Wald, Anna; Winer, Rachel L.; Holmes, King K.] Univ Washington, Seattle, WA 98195 USA. [Gaydos, Charlotte A.] Johns Hopkins Univ, Baltimore, MD USA. [Warren, Terri] Westover Hts Clin, Portland, OR USA. [Cook, Robert L.] Univ Florida, Gainesville, FL USA. [Deal, Carolyn D.; Rogers, M. Elizabeth] NIAID, Bethesda, MD 20892 USA. [Schachter, Julius] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Martin, David H.] Louisiana State Univ, New Orleans, LA USA. RP Hobbs, MM (reprint author), Univ N Carolina, Sch Med, Dept Med, CB 7031, Chapel Hill, NC 27599 USA. EM mmhobbs@med.unc.edu RI Gaydos, Charlotte/E-9937-2010; Wald, Anna/B-6272-2012 OI Wald, Anna/0000-0003-3486-6438 FU NIAID NIH HHS [U19-AI031494, U19 AI031448, U19 AI031494, U19 AI031496, U19 AI045429, U19 AI061972, U19 AI062150, U19-AI031448, U19-AI031496, U19-AI045429, U19-AI061972, U19-AI062150] NR 70 TC 53 Z9 53 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JAN PY 2008 VL 35 IS 1 BP 8 EP 13 DI 10.1097/OLQ.0b013e31815d968d PG 6 WC Infectious Diseases SC Infectious Diseases GA 245YE UT WOS:000251973900002 PM 18157061 ER PT J AU Blake, DR Quinn, TC Gaydos, CA AF Blake, Diane R. Quinn, Thomas C. Gaydos, Charlotte A. TI Should asymptomatic men be included in chlamydia screening programs? Cost-effectiveness of chlamydia screening among male and female entrants to a national job training program SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID LIGASE CHAIN-REACTION; PELVIC-INFLAMMATORY-DISEASE; SEXUALLY-TRANSMITTED-DISEASES; NUCLEIC-ACID AMPLIFICATION; URINE LEUKOCYTE ESTERASE; HIGH-RISK YOUTH; PACE 2 ASSAY; TRACHOMATIS INFECTION; NEISSERIA-GONORRHOEAE; COBAS AMPLICOR AB Objective: To compare the cost-effectiveness of various chlamydia screening strategies within a population of male and female youth entering a national job training program. Study Design: Cost-effectiveness analysis of various chlamydia screening strategies among a cohort of 4000 female and male New England job training students. Strategies for women include (a) no screening, (b) universal endocervileal DNA probe screening, (c) universal urine based NAAT screening, and (d) universal endocervical NAAT screening. Strategies for men include (a) no screening, (b) selective urine NAAT screening of leukocyte esterase (LE)-positive urines, and (c) universal urine-based NAAT screening. Results: Universal endocervical NAAT screening of Women and universal urine NAAT screening of men Were the most effective and cost-effective strategies individually and in combination. Endocervical NAAT screening of women prevented 23 more cases of PID and saved $27,000 more than endocervical DNA probe screening. Likewise, universal urine NAAT screening of men prevented 21 more cases of PID in their female partners and saved $16,000 more than selective urine NAAT screening of LE positive men. Conclusions: Use of a sensitive NAAT to screen both men and women for chlamydia upon entry to a National Job Training Program is cost-effective, cost-saving, and provides a public health opportunity to substantially reduce chlamydia C1 [Blake, Diane R.] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01655 USA. [Quinn, Thomas C.; Gaydos, Charlotte A.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA. RP Blake, DR (reprint author), Univ Massachusetts, Sch Med, Dept Pediat, 55 Lake Ave N, Worcester, MA 01655 USA. EM Diane.Blake@umassmed.edu RI Gaydos, Charlotte/E-9937-2010 FU NIAID NIH HHS [AI42845, K23 AI01750] NR 96 TC 13 Z9 14 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JAN PY 2008 VL 35 IS 1 BP 91 EP 101 DI 10.1097/OLQ.0b013e31814b86f5 PG 11 WC Infectious Diseases SC Infectious Diseases GA 245YE UT WOS:000251973900019 PM 18217229 ER PT S AU Groll, AH Walsh, TJ AF Groll, Andreas H. Walsh, Thomas J. BE Aronson, JK TI Antifungal drugs SO SIDE EFFECTS OF DRUGS ANNUAL 30: A WORLDWIDE YEARLY SURVEY OF NEW DATA AND TRENDS IN ADVERSE DRUG REACTIONS AND INTERACTIONS SE Side Effects of Drugs Annual LA English DT Article; Book Chapter ID B LIPID COMPLEX; INVASIVE FUNGAL-INFECTIONS; HUMAN LIVER-MICROSOMES; LIPOSOMAL AMPHOTERICIN-B; STEM-CELL TRANSPLANT; HEALTHY-VOLUNTEERS; MICAFUNGIN PHARMACOKINETICS; HEMATOLOGICAL MALIGNANCIES; IMMUNOCOMPROMISED PATIENTS; PLASMA-CONCENTRATIONS C1 [Groll, Andreas H.] Univ Childrens Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, Munster, Germany. [Groll, Andreas H.] Univ Childrens Hosp, Dept Hematol Oncol, Munster, Germany. [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Groll, AH (reprint author), Univ Childrens Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, Munster, Germany. EM grollan@ukmuenster.de; walsht@mail.nih.gov NR 89 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBLISHERS BV BIOMEDICAL DIVISION PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-6080 BN 978-0-08-093151-7 J9 SIDE EFFECT JI Side Eff. Drug Annu. PY 2008 VL 30 BP 316 EP 335 DI 10.1016/S0378-6080(08)00027-5 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCW81 UT WOS:000311795700028 ER PT J AU Boyce, S MacAuslan, J Carr, W Picchioni, D Braun, A Balkin, T AF Boyce, S. MacAuslan, J. Carr, W. Picchioni, D. Braun, A. Balkin, T. TI Automatic detection of changes in speech clarity during sleep deprivation SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Carr, W.] USN, Med Res Ctr, Silver Spring, MD USA. [Boyce, S.] Univ Cincinnati, Cincinnati, OH USA. [MacAuslan, J.] Speech Technol & Appl Res Corp, Bedford, MA USA. [Picchioni, D.; Balkin, T.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Carr, W.; Picchioni, D.; Braun, A.] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 341 BP A113 EP A114 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000341 ER PT J AU Carr, W Picchioni, D Balkin, TJ Matute, F Deng, H Paggi, M Braun, AR AF Carr, W. Picchioni, D. Balkin, T. J. Matute, F. Deng, H. Paggi, M. Braun, A. R. TI Effect of sleep deprivation on neural activation during language comprehension and production SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Carr, W.; Picchioni, D.; Matute, F.; Braun, A. R.] USN, Med Res Ctr, Silver Spring, MD USA. [Carr, W.; Picchioni, D.; Matute, F.; Braun, A. R.] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. [Picchioni, D.; Balkin, T. J.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Matute, F.] George Washington Univ, Washington, DC USA. [Deng, H.] Thomas Jefferson High Sch Sci & Technol, Alexandria, VA USA. [Paggi, M.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 342 BP A114 EP A114 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000342 ER PT J AU Flynn, KE Shelby, R Krystal, A Reeve, BB Mitchell, S Buysse, D Keefe, F Weinfurt, KP AF Flynn, K. E. Shelby, R. Krystal, A. Reeve, B. B. Mitchell, S. Buysse, D. Keefe, F. Weinfurt, K. P. CA PROMIS Sleep Wake Functioning Subc TI Sleep/wake functioning during and following cancer SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Flynn, K. E.; Shelby, R.; Krystal, A.; Keefe, F.; Weinfurt, K. P.; PROMIS Sleep Wake Functioning Subc] Duke Univ, Sch Med, Durham, NC USA. [Reeve, B. B.; PROMIS Sleep Wake Functioning Subc] NCI, Bethesda, MD 20892 USA. [PROMIS Sleep Wake Functioning Subc] Evanston NW Healthcare, Evanston, IL USA. [Mitchell, S.] NIH, Bethesda, MD 20892 USA. [Buysse, D.; PROMIS Sleep Wake Functioning Subc] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RI Flynn, Kathryn/M-5346-2013 OI Flynn, Kathryn/0000-0002-4427-3583 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 0906 BP A298 EP A298 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001335 ER PT J AU Griswold, BF Sloper, L Francomano, CA McDonnell, NB AF Griswold, B. F. Sloper, L. Francomano, C. A. McDonnell, N. B. TI Sleep abnormalities in patients with ehlers danlos syndromes: Related to chronic pain or an independent entity? SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Griswold, B. F.; Sloper, L.; McDonnell, N. B.] NIA, NIH, Baltimore, MD 21224 USA. [Francomano, C. A.] Greater Baltimore Med Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 0943 BP A310 EP A310 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001372 ER PT J AU Gulyani, S Maudsley, S Ferre, S Martin, B Allen, RP Mattson, MP Earley, CJ AF Gulyani, S. Maudsley, S. Ferre, S. Martin, B. Allen, R. P. Mattson, M. P. Earley, C. J. TI Iron deficiency results in increased adenosine A2A receptor signaling in human neuroblastoma cells SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Gulyani, S.; Allen, R. P.; Earley, C. J.] Johns Hopkins Univ, Baltimore, MD USA. [Maudsley, S.] NIA, IRP, NIH, DHHS,Receptor Pharmacol Unit, Baltimore, MD 21224 USA. [Ferre, S.] Natl Inst Drug Abuse, IRP, NIH, DHHS, Baltimore, MD USA. [Maudsley, S.; Martin, B.; Mattson, M. P.] NIA, IRP, NIH, DHHS,Lab Neurosci, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 840 BP A275 EP A275 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001269 ER PT J AU Kay, D Higley, J Suomi, SJ AF Kay, D. Higley, J. Suomi, S. J. TI Biological and behavioral correlates of daytime sleep/wake states in neonatal Rhesus Macaques SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD SP Amer Acad Sleep Med, Sleep Res Soc C1 [Kay, D.] Univ Florida, Gainesville, FL USA. [Higley, J.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Suomi, S. J.] NICHD, NIH, Comparat Ethol Lab, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 267 BP A88 EP A88 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000267 ER PT J AU Mancao, C Maudsley, S Gulyani, S Ferre, S Allen, RP Mattson, MP Earley, CJ AF Mancao, C. Maudsley, S. Gulyani, S. Ferre, S. Allen, R. P. Mattson, M. P. Earley, C. J. TI Regulation of neuronal dopamine receptor signaling by iron chelation SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Mancao, C.; Gulyani, S.; Allen, R. P.; Earley, C. J.] Johns Hopkins Univ, Baltimore, MD USA. [Maudsley, S.] NIA, Receptor Pharmacol Unit, IRP, NIH,DHHS, Baltimore, MD USA. [Maudsley, S.; Mattson, M. P.] NIA, Neurosci Lab, IRP, NIH,DHHS, Baltimore, MD USA. [Ferre, S.] Natl Inst Drug Abuse, IRP, NIH, DHHS, Baltimore, MD USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 810 BP A265 EP A266 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001239 ER PT J AU Pearson, V Quiroz, C Gulyani, S Allen, RP Earley, CJ Ferre, S AF Pearson, V Quiroz, C. Gulyani, S. Allen, R. P. Earley, C. J. Ferre, S. TI Iron deficiency in rats results in functional up-regulation of adenosine A2A receptors and functional down-regulation of adenosine A1 receptors SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Pearson, V; Gulyani, S.; Allen, R. P.; Earley, C. J.] Johns Hopkins Univ, Baltimore, MD USA. [Pearson, V; Quiroz, C.; Ferre, S.] NIDA IRP NIH DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 811 BP A266 EP A266 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419001240 ER PT J AU Picchioni, D Carr, WS Krugler, AL Smith, KL Shamim, SA Sato, S Braun, AR Balkin, TJ AF Picchioni, D. Carr, W. S. Krugler, A. L. Smith, K. L. Shamim, S. A. Sato, S. Braun, A. R. Balkin, T. J. TI Baseline sleep propensity predicts individual differences in performance during subsequent sleep deprivation SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Picchioni, D.; Krugler, A. L.; Smith, K. L.; Balkin, T. J.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Carr, W. S.] USN, Med Res Ctr, Silver Spring, MD USA. [Shamim, S. A.; Sato, S.; Braun, A. R.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 359 BP A120 EP A120 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000359 ER PT J AU Scharf, SM Williams, AL Chen, L Wu, J AF Scharf, S. M. Williams, A. L. Chen, L. Wu, J. TI Short term chronic intermittent hypoxia leads to cardiac dysfunction and oxidative stress SO SLEEP LA English DT Meeting Abstract CT 22nd Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 07-12, 2008 CL Baltimore, MD C1 [Scharf, S. M.; Williams, A. L.; Chen, L.; Wu, J.] Univ Maryland, Baltimore, MD 21201 USA. [Williams, A. L.] NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2008 VL 31 SU S MA 550 BP A182 EP A182 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 294PW UT WOS:000255419000550 ER PT S AU Esteban, PF Caprari, P Yoon, HY Randazzo, PA Tessarollo, L AF Esteban, Pedro F. Caprari, Paola Yoon, Hye-Young Randazzo, Paul A. Tessarollo, Lino BE Balch, WE Der, CJ Hall, A TI In vitro and in vivo analysis of neurotrophin-3 activation of Arf6 and Rac-1 SO SMALL GTPASES IN DISEASE, PART A SE Methods in Enzymology LA English DT Review; Book Chapter ID SCHWANN-CELL MIGRATION; EXCHANGE FACTOR; NEURONAL DEVELOPMENT; NERVOUS-SYSTEM; TRKC; RECEPTORS; MEMBRANE; PROTEIN; PHOSPHORYLATES; REQUIREMENT AB Arf GTP-binding proteins and Rho-family GTPases play key roles in regulating membrane remodeling and cytoskeletal reorganization involved in cell movement. Several studies have implicated neurotrophins and their receptors as upstream activators of these small GTP-binding proteins, however, the mechanisms and the cell type specificity of this neurotrophin activity are still under investigation. Here we describe the rationale and protocols used for the dissection of an NT3 activated pathway that leads to the specific activation of Arf6 and Rac1. C1 [Esteban, Pedro F.; Caprari, Paola; Tessarollo, Lino] NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Yoon, Hye-Young; Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP Esteban, PF (reprint author), NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 USA. FU Intramural NIH HHS NR 30 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-373968-1 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 438 BP 171 EP 183 DI 10.1016/S0076-6879(07)38012-9 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BHR78 UT WOS:000255834100012 PM 18413248 ER PT J AU Kim-Shapiro, DB Gladwin, MT Patel, RP Hogg, N AF Kim-Shapiro, Daniel B. Gladwin, Mark T. Patel, Rakesh P. Hogg, Neil BE Ghosh, A TI The Reaction between Nitrite and Hemoglobin: The Role of Nitrite in Hemoglobin-mediated Hypoxic Vasodilation SO SMALLEST BIOMOLECULES: DIATOMICS AND THEIR INTERACTIONS WITH HEME PROTEINS LA English DT Article; Book Chapter ID RED-BLOOD-CELLS; S-NITROSOHEMOGLOBIN; AUTOCATALYTIC OXIDATION; ISCHEMIA-REPERFUSION; HYDROGEN-PEROXIDE; IN-VIVO; OXIDE; MECHANISM; DEOXYHEMOGLOBIN; MYOGLOBIN C1 [Kim-Shapiro, Daniel B.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. [Gladwin, Mark T.] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Gladwin, Mark T.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Patel, Rakesh P.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Patel, Rakesh P.] Univ Alabama Birmingham, Ctr Free Radical Biol, Birmingham, AL 35294 USA. [Hogg, Neil] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. [Hogg, Neil] Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA. RP Kim-Shapiro, DB (reprint author), Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. OI Patel, Rakesh/0000-0002-1526-4303 NR 60 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-055632-1 PY 2008 BP 269 EP 289 DI 10.1016/B978-044452839-1.50012-7 PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEH47 UT WOS:000316610500012 ER PT J AU Brownell, C Belsky, J Booth-LaForce, C Bradley, R Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Hartup, W Houts, R Kelly, J Knoke, B McCartney, K Marshall, N O'Brien, M Owen, MT Parke, R Payne, C Pianta, R Robeson, WW Spieker, S Vandell, DL Weinraub, M AF Brownell, Celia Belsky, Jay Booth-LaForce, Cathryn Bradley, Robert Campbell, Susan B. Clarke-Stewart, K. Alison Cox, Martha Friedman, Sarah L. Hirsh-Pasek, Kathryn Hartup, Willard Houts, Renate Kelly, Jean Knoke, Bonnie McCartney, Kathleen Marshall, Nancy O'Brien, Marion Owen, Margaret Tresch Parke, Ross Payne, Chris Pianta, Robert Robeson, Wendy Wagner Spieker, Susan Vandell, Deborah Lowe Weinraub, Marsha CA NICHD TI Social competence with peers in third grade: Associations with earlier peer experiences in childcare SO SOCIAL DEVELOPMENT LA English DT Article DE peer relations; childcare; friendship; social competence ID INFANT DAY-CARE; CORTISOL CONCENTRATIONS; PRESCHOOLERS; QUALITY; BEHAVIOR; EMOTIONALITY; TEMPERAMENT; ADJUSTMENT; TODDLERS; OUTCOMES AB The early developmental antecedents of individual differences in children's social functioning with peers in third grade were examined using longitudinal data from the large-scale National Institute of Child Health and Human Development (NICHD) study of early child care. In a sample of 1,364 children, with family and child factors controlled, the frequency of positive and negative peer interactions in childcare between 24 and 54 months and the number of hours spent in childcare peer groups of different sizes (alone, dyad, small, medium, large) predicted third graders' peer competence at three levels of analysis: individual social skills, dyadic friendships, and peer-group acceptance. Children who had more positive experiences with peers in childcare had better social and communicative skills with peers in third grade, were more sociable and co-operative and less aggressive, had more close friends, and were more accepted and popular. Children with more frequent negative experiences with peers in childcare were more aggressive in third grade, had lower social and communicative skills, and reported having fewer friends. When children spent more time in small-sized peer groups in childcare (four or fewer children at 24 months of age up to seven or fewer at 54 months), they were more sociable and co-operative in third grade, but their teachers rated them as more aggressive, suggesting that such children may be more socially outgoing and active both positively and negatively. Like those who spent more time in small peer groups, children who spent more hours in medium-sized groups received higher ratings for peer aggression by their third-grade teachers. Children who spent more time with one other child in childcare or in small peer groups had fewer classroom friends in third grade as reported by the teacher but not according to maternal report or self-report. There were no significant associations between the amount of time children spent in large childcare-based peer groups and third-grade peer social competence. C1 [Brownell, Celia; Campbell, Susan B.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Belsky, Jay] Birkbeck Univ London, London, England. [Booth-LaForce, Cathryn; Kelly, Jean; Spieker, Susan] Univ Washington, Seattle, WA 98195 USA. [Bradley, Robert] Univ Arkansas, Little Rock, AR 72204 USA. [Clarke-Stewart, K. Alison] Univ Calif Irvine, Irvine, CA USA. [Cox, Martha] Univ N Carolina, Chapel Hill, NC USA. [Friedman, Sarah L.] NICHD, Bethesda, MD USA. [Hirsh-Pasek, Kathryn; Weinraub, Marsha] Temple Univ, Philadelphia, PA 19122 USA. [Houts, Renate; Knoke, Bonnie] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [McCartney, Kathleen] Harvard Univ, Cambridge, MA 02138 USA. [Marshall, Nancy; Robeson, Wendy Wagner] Wellesley Coll, Wellesley, MA 02181 USA. [O'Brien, Marion; Payne, Chris] Univ N Carolina, Greensboro, NC 27412 USA. [Owen, Margaret Tresch] Univ Texas Dallas, Dallas, TX 75230 USA. [Parke, Ross] Univ Calif Riverside, Riverside, CA 92521 USA. [Pianta, Robert] Univ Virginia, Charlottesville, VA 22903 USA. [Vandell, Deborah Lowe] Univ Wisconsin Madison, Madison, WI USA. RP Brownell, C (reprint author), Univ Pittsburgh, Dept Psychol, 3137 Sennott Sq, Pittsburgh, PA 15260 USA. EM brownell@pitt.edu RI Marshall, Nancy/C-3428-2012 NR 89 TC 3 Z9 3 U1 6 U2 33 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0961-205X J9 SOC DEV JI Soc. Dev. PY 2008 VL 17 IS 3 BP 419 EP 453 DI 10.1111/j.1467-9507.2007.00446.x PG 35 WC Psychology, Developmental SC Psychology GA 327AD UT WOS:000257700200002 ER PT J AU Mayer, KH Pizer, HF AF Mayer, Kenneth H. Pizer, H. F. BE Mayer, KH Pizer, HF TI Introduction: What constitutes the social ecology of infectious diseases? SO SOCIAL ECOLOGY OF INFECTIOUS DISEASES LA English DT Editorial Material; Book Chapter AB Infectious disease is one of the great tragedies of living things - the struggle for existence between different forms of life. Man sees it from his own prejudiced point of view; but clams, oysters, insects, fish, flowers, tobacco, potatoes, tomatoes, fruit, shrubs, trees, have their own varieties of smallpox, measles, cancer, or tuberculosis. Incessantly, the pitiless war goes on, without quarter or armistice - a nationalism of species against species. The important point is that infectious disease is merely a disagreeable instance of a widely prevalent tendency of all living creatures to save themselves the bother of building, by their own efforts, the things they require. Whenever they find it possible to take advantage of the constructive labors of others, this is the direction of the least resistance. About the only genuine sporting proposition that remains unimpaired by the relentless domestication of a once free-living human species is the war against these ferocious little fellow creatures, which lurk in the dark corners and stalk us in the bodies of rats, mice, and all kinds of domestic animals; which fly and crawl with the insects, and waylay us in our food and drink and even in our love. C1 [Mayer, Kenneth H.] Brown Univ, Providence, RI 02912 USA. [Mayer, Kenneth H.] Brown Univ, AIDS Program, Providence, RI 02912 USA. [Mayer, Kenneth H.] Miriam Hosp, Div Infect Dis, Providence, RI 02906 USA. [Mayer, Kenneth H.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Mayer, Kenneth H.] Bostons Fenway Community Hlth Ctr, Boston, MA USA. [Mayer, Kenneth H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Mayer, Kenneth H.] Brown Univ, Fogarty NIH AIDS Int Res & Training Program, Providence, RI 02912 USA. [Mayer, Kenneth H.] Tufts Univ, Fogarty NIH AIDS Int Res & Training Program, Medford, MA 02155 USA. [Mayer, Kenneth H.] NIH, Data Safety & Monitoring Board, AIDS Clin Trials Grp, Bethesda, MD USA. RP Mayer, KH (reprint author), Brown Univ, Providence, RI 02912 USA. NR 4 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-055714-4 PY 2008 BP 1 EP 16 PG 16 WC Infectious Diseases SC Infectious Diseases GA BFE74 UT WOS:000319510600002 ER PT J AU Gardner, P Primack, A Rosenthal, JP Bridbord, K AF Gardner, Pierce Primack, Aron Rosenthal, Joshua P. Bridbord, Kenneth BE Mayer, KH Pizer, HF TI Principles of building the global health workforce SO SOCIAL ECOLOGY OF INFECTIOUS DISEASES LA English DT Article; Book Chapter C1 [Gardner, Pierce] SUNY Stony Brook, Sch Med, New York, NY USA. [Gardner, Pierce] Ctr Dis Control, Amer Coll Phys, Advisory Comm Immunizat Practices, Atlanta, GA 30333 USA. [Gardner, Pierce] CDC, Epidem Intelligence Serv, Atlanta, GA 30333 USA. [Gardner, Pierce] CDC, Cent Nervous Syst Viral Surveillance Unit, Atlanta, GA 30333 USA. [Gardner, Pierce] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gardner, Pierce] Univ Chicago, Chicago, IL 60637 USA. [Gardner, Pierce] SUNY Stony Brook, Stony Brook, NY USA. [Primack, Aron] NIH, Fogarty Int Ctr, Bethesda, MD USA. [Primack, Aron] US Hlth Care Financing Adm, Program Integr, Washington, DC USA. [Primack, Aron] US Hlth Care Financing Adm, Ctr Hlth Plans & Providers, Washington, DC USA. [Primack, Aron] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Bridbord, Kenneth] US EPA, Washington, DC USA. RP Gardner, P (reprint author), SUNY Stony Brook, Sch Med, New York, NY USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-055714-4 PY 2008 BP 449 EP 463 DI 10.1016/B978-012370466-5.50022-4 PG 15 WC Infectious Diseases SC Infectious Diseases GA BFE74 UT WOS:000319510600019 ER PT J AU Vinikoor, LC Kaufman, JS MacLehose, RF Laraia, BA AF Vinikoor, Lisa C. Kaufman, Jay S. MacLehose, Richard F. Laraia, Barbara A. TI Effects of racial density and income incongruity on pregnancy outcomes in less segregated communities SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE pregnancy; segregation; social class; low birth weight; preterm delivery; Bayesian logistic regression; USA; ethnicity AB A previous publication in this journal documented a decreased risk of adverse birth outcomes when African-American women have a positive income incongruity (defined as mothers living in a census tract with a higher household income than would be expected based on their individual education and marital status) and live in a census tract with "predominately African-American" residents [Pickett, K. E., Collins, J. W. Jr., Masi, C. M., & Wilkinson, R. G. (2005). The effects of racial density and income incongruity on pregnancy outcomes. Social Science & Medicine, 60(10), 2229-2238.]. The communities included in that study were from Chicago and were highly segregated by race. Our objective was to repeat this analysis in a less severely segregated environment: two urban counties (Wake and Durham) in central North Carolina. Rather than assuming an absence of knowledge about the effects of interest, we used the previously published results to inform our prior distributions in a Bayesian logistic regression analysis. This approach, which is analogous to a meta-analysis of the two studies, revealed a protective effect of positive income incongruity for African-American women living in census tracts with high relative African-American density across a much wider range of residential segregation patterns. Positive income incongruity was not associated with a decreased risk of low birth weight or preterm delivery for women living in tracts with a low relative density of African-Americans. These estimates are comparable to those that might have been observed had the original authors included a much more diverse set of communities with respect to degree of segregation, and so these new results provide important information about the generality of this intriguing finding. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Vinikoor, Lisa C.; Kaufman, Jay S.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA. [MacLehose, Richard F.] NIEHS, Bethesda, MD USA. RP Vinikoor, LC (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA. EM vinikoor@email.unc.edu; jay_kaufman@unc.edu; maclehoser@niehs.nih.gov; laraiab@chc.ucsf.edu FU Intramural NIH HHS; NICHD NIH HHS [K01 HD047122]; PHS HHS [R40 MC 07841-01] NR 6 TC 17 Z9 17 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JAN PY 2008 VL 66 IS 2 BP 255 EP 259 DI 10.1016/j.socscimed.2007.08.016 PG 5 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 257TS UT WOS:000252822000005 PM 17920176 ER PT J AU Mokuau, N Braun, KL Wong, LK Higuchi, P Gotay, CC AF Mokuau, Noreen Braun, Kathryn L. Wong, Linda K. Higuchi, Paula Gotay, Carolyn C. TI Development of a family intervention for native Hawaiian women with cancer: A pilot study SO SOCIAL WORK LA English DT Article DE culture; feasibility study; Hawai'i; kinship networks; oncology services; social values ID SURVIVAL; SPIRITUALITY; BREAST AB Native Hawaiian women have high cancer rates and low survival rates. As with other women, a major source of support for Native Hawaiian women is their families. This pilot study reports on the feasibility of providing and measuring a culturally appropriate intervention designed to help Native Hawaiian women and their families deal with cancer. The feasibility evaluation indicated that a major strength of the intervention was its incorporation of Hawaiian values and practices, and a major limitation reflected the difficulties in recruiting Native Hawaiians for research studies. Despite the small sample size, the six Native Hawaiian women and their 10 family members in the intervention group showed improved self-efficacy and coping when compared with the four Native Hawaiian women and their eight family members in the control group. Pilot study data established the feasibility and potential effectiveness of this culturally tailored intervention for Native Hawaiians, and feasibility findings will be useful in designing follow-up studies. Steps taken to incorporate cultural values into an intervention also provide a model for other social workers in developing culturally appropriate interventions for minority populations. C1 [Mokuau, Noreen; Braun, Kathryn L.] Univ Hawaii, Sch Social Work, Honolulu, HI 96822 USA. [Braun, Kathryn L.] Imi Hale Nat Hawaiian Canc Network, Honolulu, HI USA. [Wong, Linda K.] Nat Hawaiian Hlth Care Syst, Honolulu, HI USA. [Higuchi, Paula; Gotay, Carolyn C.] Univ Hawaii, Canc Res Ctr Hawaii, Canc Informat Serv, Natl Canc Inst, Honolulu, HI 96813 USA. RP Mokuau, N (reprint author), Univ Hawaii, Sch Social Work, 1800 East West Rd, Honolulu, HI 96822 USA. EM noreen@hawaii.edu FU NCI NIH HHS [U01-CA86105-03] NR 33 TC 13 Z9 14 U1 3 U2 6 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 USA SN 0037-8046 J9 SOC WORK JI Soc. Work PD JAN PY 2008 VL 53 IS 1 BP 9 EP 19 PG 11 WC Social Work SC Social Work GA 282UI UT WOS:000254592300002 PM 18610817 ER PT J AU O'Donnell, P Farrar, A BrintzenhofeSzoc, K Conrad, AP Danis, M Grady, C Taylor, C Ulrich, CM AF O'Donnell, Patricia Farrar, Adrienne BrintzenhofeSzoc, Karlynn Conrad, Ann Patrick Danis, Marion Grady, Christine Taylor, Carol Ulrich, Connie M. TI Predictors of ethical stress, moral action and job satisfaction in health care social workers SO SOCIAL WORK IN HEALTH CARE LA English DT Article DE ethical stress; moral action; health care social workers; job satisfaction ID GENERAL HOSPITALS; DECISION-MAKING; HOME-CARE; DILEMMAS; LIFE; END; ENVIRONMENT; MANAGEMENT; DISTRESS; AUTONOMY AB Value conflicts can be a source of ethical stress for social workers in health care settings. That stress, unless mediated by the availability of ethical resource services, can lead to social workers' dissatisfaction with their positions and careers, and possibly result in needed professionals leaving the field.. This study explored social workers experiences in dealing with-ethical issues in health care settings. Findings showed the inter-relationship between selected individual and organizational factors and overall ethical stress, the ability to take moral actions; the impact of ethical stress on job satisfaction, and the intent to leave position. C1 [O'Donnell, Patricia] Inova Hlth Syst, Ctr Eth, Springfield, VA 22151 USA. [Farrar, Adrienne] NIH, Ctr Clin, Dept Social Work, Bethesda, MD 20892 USA. [BrintzenhofeSzoc, Karlynn; Conrad, Ann Patrick] Catholic Univ Amer, Natl Catholic Sch Social Serv, Washington, DC 20064 USA. [Danis, Marion; Grady, Christine] NIH, Clin Bioeth Dept, Bethesda, MD 20892 USA. [Taylor, Carol] Georgetown Univ, Ctr Clin Bioeth, Washington, DC USA. [Ulrich, Connie M.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP O'Donnell, P (reprint author), Inova Hlth Syst, Ctr Eth, 8003 Forbes Pl, Springfield, VA 22151 USA. EM patricia.o'donnell@inova.com FU Intramural NIH HHS [Z01 CL010523-06] NR 57 TC 10 Z9 10 U1 1 U2 15 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0098-1389 J9 SOC WORK HEALTH CARE JI Soc. Work Health Care PY 2008 VL 46 IS 3 BP 29 EP 51 DI 10.1300/J010v46n03_02 PG 23 WC Social Work SC Social Work GA 277EW UT WOS:000254196500002 PM 18551828 ER PT J AU Lin, DC Horkay, F AF Lin, David C. Horkay, Ferenc TI Nanomechanics of polymer gels and biological tissues: A critical review of analytical approaches in the Hertzian regime and beyond SO SOFT MATTER LA English DT Review ID ATOMIC-FORCE MICROSCOPY; LIVING CELLS; MICROMECHANICAL PROPERTIES; MECHANICAL-PROPERTIES; ELASTIC-MODULUS; ELECTROLYTE-SOLUTIONS; SENSING INDENTATION; ROBUST STRATEGIES; CURVE ANALYSIS; ADHESION AB We survey recent progress in the application of nanoindentation to characterize the local mechanical properties of polymer gels and biological tissues. We review the theories, analytical models based thereon, and data processing techniques commonly used to determine elastic properties of these classes of materials by instrumented nanoindentation. Examples from the testing of synthetic and biological gels are used to illustrate the limitations of existing theories and approaches. Emphasis is placed on the need for contact mechanics models that more accurately represent the large-strain behaviour of soft matter. C1 [Lin, David C.; Horkay, Ferenc] Natl Inst Hlth, Natl Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Lin, DC (reprint author), Natl Inst Hlth, Natl Integrat & Med Biophys, Bethesda, MD 20892 USA. EM lindavid@mail.nih.gov; horkay@helix.nih.gov NR 81 TC 74 Z9 74 U1 3 U2 62 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X J9 SOFT MATTER JI Soft Matter PY 2008 VL 4 IS 4 BP 669 EP 682 DI 10.1039/b714637j PG 14 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 279WV UT WOS:000254386800005 ER PT J AU Dhungana, S Crumbliss, AL AF Dhungana, Suraj Crumbliss, Alvin L. BE Kaim, W Klein, A TI UV-Vis Spectroelectrochemistry of Selected Iron-Containing Proteins SO SPECTROELECTROCHEMISTRY LA English DT Article; Book Chapter ID HUMAN TRANSFERRIN RECEPTOR; FERRIC BINDING-PROTEIN; REDOX PROPERTIES; CRYSTAL-STRUCTURE; BACTERIAL TRANSFERRIN; SERUM TRANSFERRIN; ELECTRON-TRANSFER; NITRIC-OXIDE; HEMOGLOBIN; REDUCTION C1 [Dhungana, Suraj] Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Crumbliss, Alvin L.] Duke Univ, Dept Chem, Durham, NC 27708 USA. RP Dhungana, S (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, DHHS, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. NR 73 TC 3 Z9 3 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND BN 978-1-84755-840-4 PY 2008 BP 31 EP 67 DI 10.1039/9781847558404-00031 D2 10.1039/9781847558404 PG 37 WC Chemistry, Physical SC Chemistry GA BKW88 UT WOS:000269492400003 ER PT J AU Rogers, CJ Colbert, LH Greiner, JW PerkinS, SN Hursting, SD AF Rogers, Connie J. Colbert, Lisa H. Greiner, John W. PerkinS, Susan N. Hursting, Stephen D. TI Physical activity and cancer prevention - Pathways and targets for intervention SO SPORTS MEDICINE LA English DT Review ID NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; RAT SKELETAL-MUSCLE; BLOOD MONONUCLEAR-CELLS; MACROPHAGE ANTITUMOR CYTOTOXICITY; INDUCED MAMMARY TUMORIGENESIS; INDUCED OXIDATIVE STRESS; GROWTH-FACTOR-I; MALE F344 RATS; NF-KAPPA-B AB The prevalence of obesity, an established epidemiological risk factor for many cancers, has risen steadily for the past several decades in the US and many other countries. Particularly alarming are the increasing rates of obesity among children, portending continuing increases in the rates of obesity and obesity-related cancers for many years to come. Modulation of energy balance, via increased physical activity, has been shown in numerous comprehensive epidemiological reviews to reduce cancer risk. Unfortunately, the effects and mechanistic targets of physical activity interventions on the carcinogenesis process have not been thoroughly characterized. Studies to date suggest that exercise can exert its cancer-preventive effects at many stages during the process of carcinogenesis, including both tumour initiation and progression. As discussed in this review, exercise may be altering tumour initiation events by modifying carcinogen activation, specifically by enhancing the cytochrome P450 system and by enhancing selective enzymes in the carcinogen detoxification pathway, including, but not limited to, glutathione-S-transferases. Furthermore, exercise may reduce oxidative damage by increasing a variety of anti-oxidant enzymes, enhancing DNA repair systems and improving intracellular protein repair systems. In addition to altering processes related to turnout initiation, exercise may also exert a cancer-preventive effect by dampening the processes involved in the promotion and progression stages of carcinogenesis, including scavenging reactive oxygen species (ROS); altering cell proliferation, apoptosis and differentiation; decreasing inflammation; enhancing immune function; and suppressing angiogenesis. A paucity of data exists as to whether exercise may be working as an anti-promotion strategy via altering ROS in initiated or preneoplastic models; therefore, no conclusions can be made about this possible mechanism. The studies directly examining cell proliferation and apoptosis have shown that exercise can enhance both processes, which is difficult to interpret in the context of carcinogenesis. Studies examining the relationship between exercise and chronic inflammation suggest that exercise may reduce pro-inflammatory mediators and reduce the state of low-grade, chronic inflammation. Additionally, exercise has been shown to enhance components of the innate immune response (i.e. macrophage and natural killer cell function). Finally, only a limited number of studies have explored the relationship between exercise and angiogenesis; therefore, no conclusions can be made currently about the role of exercise in the angiogenesis process as it relates to tumour progression. In summary, exercise can alter biological processes that contribute to both anti-initiation and anti-progression events in the carcinogenesis process. However, more sophisticated, detailed studies are needed to examine each of the potential mechanisms contributing to an exercise-induced decrease in carcinogenesis in order to determine the minimum dose, duration and frequency of exercise needed to yield significant cancer-preventive effects, and whether exercise can be used prescriptively to reverse the obesity-induced physiological changes that increase cancer risk. C1 [PerkinS, Susan N.; Hursting, Stephen D.] Univ Texas Austin, MD Anderson Canc Ctr, Div Nutr Sci, Univ Stn 1, Austin, TX 78712 USA. [Rogers, Connie J.; Greiner, John W.] Natl Canc Inst, Tumor Immunol & Biol Lab, Canc Res Ctr, Bethesda, MD USA. [Rogers, Connie J.] Natl Canc Inst, Canc Prevent Div, Canc Prevent Fellowship Program, Bethesda, MD USA. [Colbert, Lisa H.] Univ Wisconsin, Dept Kinesiol, Madison, WI USA. [Hursting, Stephen D.] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA. RP Hursting, SD (reprint author), Univ Texas Austin, MD Anderson Canc Ctr, Div Nutr Sci, Univ Stn 1, A2700,Painter Hall,Room 5-32, Austin, TX 78712 USA. EM shursting@mail.utexas.edu NR 245 TC 63 Z9 64 U1 0 U2 13 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0112-1642 J9 SPORTS MED JI Sports Med. PY 2008 VL 38 IS 4 BP 271 EP 296 PG 26 WC Sport Sciences SC Sport Sciences GA 291PZ UT WOS:000255210600002 PM 18348589 ER PT S AU Zou, SG He, HJ Zong, YP Shi, LM Wang, LL AF Zou, Sige He, Hua-Jun Zong, Yaping Shi, Leming Wang, Lili BE ReschGenger, U TI DNA Microarrays: Applications, Future Trends, and the Need for Standardization SO STANDARDIZATION AND QUALITY ASSURANCE IN FLUORESCENCE MEASUREMENTS II: BIOANALYTICAL AND BIOMEDICAL APPLICATIONS SE Springer Series on Fluorescence LA English DT Article; Book Chapter DE Bead-based arrays; cDNA arrays; Expression profiling; External RNA control; Genotyping; Oligonucleotide arrays; Scanner performance validation ID GENE-EXPRESSION PATTERNS; NF-KAPPA-B; GENOME-WIDE; DROSOPHILA-MELANOGASTER; POINT MUTATIONS; OLIGONUCLEOTIDE MICROARRAY; PROTEIN EXPRESSION; OXIDATIVE STRESS; CELL MICROARRAYS; GLASS SLIDES AB Microarray technology allows high-throughput analysis of tens or even hundreds of thousands of genes in a single experiment, and has been applied broadly to address a wide variety of questions in basic and applied sciences. The applications of the microarray technology range from gene-expression profiling and genotyping to DNA-protein interactions and genome sequencing, and the list of applications keeps growing, especially when combined with other technologies such as proteomic technologies. However, many steps are involved in each microarray experiment and a number of microarray platforms exist, each with its unique features. The challenge is how to standardize the methods and materials to allow intra- and inter-comparison of microarray data collected in the same or different set of experiments. With the challenge in mind, we address the need for standardization for each step of the microarray experiments with emphasis on quality control of array fabrication and scanner calibration and verification. The proposed standards are designed for checking the quality of mRNA, fabricating slides, hybridization, and collecting, analyzing, and storing data. By implementing standards for each step of the microarray process, the full potential of the microarray technology will be realized, especially in the area of disease diagnosis and drug development. C1 [He, Hua-Jun; Wang, Lili] Natl Inst Stand & Technol, Div Biochem Sci, Gaithersburg, MD 20899 USA. [Zou, Sige; Wang, Lili] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Zong, Yaping] Full Moon Biosyst, Sunnyvale, CA 94085 USA. [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wang, LL (reprint author), Natl Inst Stand & Technol, Div Biochem Sci, 100 Bur Dr MS 8312, Gaithersburg, MD 20899 USA. EM lili.wang@nist.gov NR 83 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1617-1306 BN 978-3-540-70570-3 J9 SPRINGER SER FLUORES PY 2008 VL 06 BP 215 EP 237 DI 10.1007/4243_2008_036 D2 10.1007/978-3-540-70571-0 PG 23 WC Biochemistry & Molecular Biology; Chemistry, Analytical; Optics; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Optics; Spectroscopy GA BJV84 UT WOS:000267284000008 ER PT S AU Gaigalas, AK Wang, LL AF Gaigalas, A. K. Wang, Lili BE ReschGenger, U TI Approaches to Quantitation in Flow Cytometry SO STANDARDIZATION AND QUALITY ASSURANCE IN FLUORESCENCE MEASUREMENTS II: BIOANALYTICAL AND BIOMEDICAL APPLICATIONS SE Springer Series on Fluorescence LA English DT Article; Book Chapter DE Antibodies; Calibration; Flow cytometry; Fluorescence; MESF; Microspheres; Quantitative ID ANTIBODY-BINDING CAPACITY; INDIRECT IMMUNOFLUORESCENCE; FLUORESCENCE INTENSITY; MONOCLONAL-ANTIBODIES; ANTIGEN-EXPRESSION; STANDARDS; TRACEABILITY; LYMPHOCYTES; PERFORMANCE; FLUOROMETRY AB Flow cytometry is used to measure the fluorescence intensity (FI) from labels bound to antigens present on the surface of T and B cells. The T and B cells are associated with the human adaptive immune system and the amounts of surface antigens, such as CD4, CD8, and CD20, are used for diagnostic purposes. To estimate the number of a specific antigen expressed on the surface, the cells are incubated in a solution containing antibodies specific to that antigen and the antibodies are conjugated to fluorophores that provide the fluorescence signals used to detect the presence of the antibodies on the cell surface. The fluorophore on the antibody, microsphere, or cell is called a label. The antibody gives biological specificity and the fluorophore provides a mechanism for readout. Quantitation of cytometer measurements is accomplished by the comparison of the fluorescence signal of labeled cells with the fluorescence signal of labeled reference microspheres. The fluorescence signals from labeled cells and labeled microspheres are converted to a fluorescence yield (FY) where FY is defined as the product of the number of fluorophores and the fluorophore quantum yield. The comparison of fluorescence provides the basis for an estimate of the number of molecules of equivalent soluble fluorophores (MESF) associated with the labels bound on the cell surface. A procedure is outlined for assigning MESF values to microspheres followed by a demonstration of the assignment of MESF values to microspheres with immobilized R-phycoerythrin. The MESF values are used to obtain an estimate of the antibodies bound to the cell (ABCe). The final step in the quantitation process is the conversion of the ABCe values to an estimate of the number of specific antigens on a surface of a cell. With proper care, the ABCe value may be a good indicator of the total number of specific antigens present on the cell surface. Examples are given of the determination of the number of CD4 and CD20 antigens on lymphocytes. The MESF quantitation strategy has been applied to the calibration of multicolor flow cytometers. C1 [Gaigalas, A. K.; Wang, Lili] Natl Inst Stand & Technol, Div Biochem Sci, Gaithersburg, MD 20899 USA. [Wang, Lili] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Gaigalas, AK (reprint author), Natl Inst Stand & Technol, Div Biochem Sci, 100 Bur Dr MS 8312, Gaithersburg, MD 20899 USA. EM adolfas.gaigalas@nist.gov NR 39 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1617-1306 BN 978-3-540-70570-3 J9 SPRINGER SER FLUORES PY 2008 VL 06 BP 371 EP 398 DI 10.1007/4243_2008_042 D2 10.1007/978-3-540-70571-0 PG 28 WC Biochemistry & Molecular Biology; Chemistry, Analytical; Optics; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Optics; Spectroscopy GA BJV84 UT WOS:000267284000014 ER PT S AU Holden, MJ Wang, LL AF Holden, Marcia J. Wang, Lili BE ReschGenger, U TI Quantitative Real-Time PCR: Fluorescent Probe Options and Issues SO STANDARDIZATION AND QUALITY ASSURANCE IN FLUORESCENCE MEASUREMENTS II: BIOANALYTICAL AND BIOMEDICAL APPLICATIONS SE Springer Series on Fluorescence LA English DT Article; Book Chapter DE FRET; Hybridization probe; Molecular beacon; Real-time quantitative PCR; Scorpion primer; SYBR Green I; TaqMan probe ID RESONANCE ENERGY-TRANSFER; SYBR-GREEN-I; POLYMERASE-CHAIN-REACTION; MOLECULAR BEACONS; SCORPION PRIMERS; RT-PCR; ENZYMATIC AMPLIFICATION; DNA AMPLIFICATION; QUANTIFICATION; VIRUS AB Fluorescence has played a vital role in the development of polymerase chain reaction (PCR)-based DNA amplification. In qualitative PCR, an end point reaction, the amplified DNA, is visualized using DNA intercalating fluorescent dyes. Creative uses of nucleotide probes with fluorescent tags have been developed for real-time quantitative PCR. These probes take advantage of the behavior and properties of fluorophores. There are advantages and disadvantages to various probe types as well as design considerations. Attention to these issues will help in the development of robust and accurate DNA quantification using real-time PCR. C1 [Holden, Marcia J.; Wang, Lili] Natl Inst Stand & Technol, Div Biochem Sci, Gaithersburg, MD 20899 USA. [Wang, Lili] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Holden, MJ (reprint author), Natl Inst Stand & Technol, Div Biochem Sci, 100 Bur Dr,Mail Stop 8311, Gaithersburg, MD 20899 USA. EM marcia.holden@nist.gov NR 50 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1617-1306 BN 978-3-540-70570-3 J9 SPRINGER SER FLUORES PY 2008 VL 06 BP 489 EP 508 DI 10.1007/4243_2008_046 PG 20 WC Biochemistry & Molecular Biology; Chemistry, Analytical; Optics; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Optics; Spectroscopy GA BJV84 UT WOS:000267284000019 ER PT J AU Berger, V Zhang, S Zhou, YY AF Berger, Vance Zhang, Shu Zhou, Yan Yan TI Modeling and predicting extrapolated probabilities with outlooks - Comments SO STATISTICA SINICA LA English DT Editorial Material C1 [Berger, Vance] Natl Canc Inst, Rockville, MD 20892 USA. [Zhang, Shu] Univ Maryland, Dept Math, College Pk, MD 20742 USA. [Zhou, Yan Yan] Calif State Univ Hayward, Dept Stat, Hayward, CA 94542 USA. RP Berger, V (reprint author), Natl Canc Inst, 6130 Execut Blvd, Rockville, MD 20892 USA. EM bergerv@mail.nih.gov; zhangshu@math.umd.edu; yanyan.zhou@csueastbay.edu NR 1 TC 1 Z9 1 U1 0 U2 0 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD JAN PY 2008 VL 18 IS 1 BP 55 EP 57 PG 3 WC Statistics & Probability SC Mathematics GA 261RW UT WOS:000253098700008 ER PT S AU Sundaram, R AF Sundaram, Rajeshwari BE Biswas, A Datta, S Fine, JP Segal, MR TI Robust Estimation for Analyzing Recurrent-Event Data in the Presence of Terminal Events SO STATISTICAL ADVANCES IN THE BIOMEDICAL SCIENCES: CLINICAL TRIALS, EPIDEMIOLOGY, SURVIVAL ANALYSIS, AND BIOINFORMATICS SE Wiley Series in Probability and Statistics LA English DT Article; Book Chapter ID MINIMUM DISTANCE ESTIMATION; REGRESSION-MODEL; SEMIPARAMETRIC INFERENCE; TRANSFORMATION MODELS; LINEAR-REGRESSION; TIME C1 NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. RP Sundaram, R (reprint author), NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. EM sundaramr2@mail.nih.gov NR 29 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND SN 1940-6517 BN 978-0-470-18121-8; 978-0-471-94753-0 J9 WILEY SER PROBAB ST PY 2008 BP 245 EP 264 PG 20 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BEE43 UT WOS:000316287100016 ER PT S AU Chatterjee, N AF Chatterjee, Nilanjan BE Biswas, A Datta, S Fine, JP Segal, MR TI Analysis of Case-Control Studies in Genetic Epidemiology SO STATISTICAL ADVANCES IN THE BIOMEDICAL SCIENCES: CLINICAL TRIALS, EPIDEMIOLOGY, SURVIVAL ANALYSIS, AND BIOINFORMATICS SE Wiley Series in Probability and Statistics LA English DT Article; Book Chapter ID DISEASE ASSOCIATIONS; LOGISTIC-REGRESSION; GENOTYPE DATA; INFERENCE; INDEPENDENCE; INFORMATION; POPULATION; HAPLOTYPES; EXPOSURE; MODELS C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. RP Chatterjee, N (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd, Rockville, MD 20852 USA. EM chattern@mail.nih.gov NR 24 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND SN 1940-6517 BN 978-0-470-18121-8 J9 WILEY SER PROBAB ST PY 2008 BP 405 EP 418 PG 14 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BEE43 UT WOS:000316287100024 ER PT J AU Guo, WG Peddada, S AF Guo, Wenge Peddada, Shyamal TI Adaptive choice of the number of bootstrap samples in large scale multiple testing SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE BH procedure; bootstrap; confidence interval; false discovery rate; multiple testing; p-value ID FALSE DISCOVERY RATE; DIFFERENTIALLY EXPRESSED GENES; ORDER-RESTRICTED INFERENCE; CONFIDENCE-INTERVALS; MICROARRAY; RATES; PROPORTION AB It is a common practice to use resampling methods such as the bootstrap for calculating the p-value for each test when performing large scale multiple testing. The precision of the bootstrap p-values and that of the false discovery rate (FDR) relies on the number of bootstraps used for testing each hypothesis. Clearly, the larger the number of bootstraps the better the precision. However, the required number of bootstraps can be computationally burdensome, and it multiplies the number of tests to be performed. Further adding to the computational challenge is that in some applications the calculation of the test statistic itself may require considerable computation time. As technology improves one can expect the dimension of the problem to increase as well. For instance, during the early days of microarray technology, the number of probes on a cDNA chip was less than 10,000. Now the Affymetrix chips come with over 50,000 probes per chip. Motivated by this important need, we developed a simple adaptive bootstrap methodology for large scale multiple testing, which reduces the total number of bootstrap calculations while ensuring the control of the FDR. The proposed algorithm results in a substantial reduction in the number of bootstrap samples. Based on a simulation study we found that, relative to the number of bootstraps required for the Benjamini-Hochberg (BH) procedure, the standard FDR methodology which was the proposed methodology achieved a very substantial reduction in the number of bootstraps. In some cases the new algorithm required as little as 1/6th the number of bootstraps as the conventional BH procedure. Thus, if the conventional BH procedure used 1,000 bootstraps, then the proposed method required only 160 bootstraps. This methodology has been implemented for time-course/dose-response data in our software, ORIOGEN, which is available from the authors upon request. C1 [Guo, Wenge; Peddada, Shyamal] Natl Inst Environm Hlth Sci, Bethesda, MD USA. RP Guo, WG (reprint author), Natl Inst Environm Hlth Sci, Bethesda, MD USA. EM wenge.guo@gmail.com; peddada@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 NR 39 TC 4 Z9 4 U1 1 U2 1 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2194-6302 EI 1544-6115 J9 STAT APPL GENET MOL JI Stat. Appl. Genet. Mol. Biol. PY 2008 VL 7 IS 1 AR 13 PG 21 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 282KY UT WOS:000254567900010 ER PT J AU Jiang, WY Varma, S Simon, R AF Jiang, Wenyu Varma, Sudhir Simon, Richard TI Calculating confidence intervals for prediction error in microarray classification using resampling SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE microarray study; class prediction; prediction error; confidence interval; resampling; bootstrap; cross-validation ID GENE-EXPRESSION DATA; CROSS-VALIDATION AB Cross-validation based point estimates of prediction accuracy are frequently reported in microarray class prediction problems. However these point estimates can be highly variable, particularly for small sample numbers, and it would be useful to provide confidence intervals of prediction accuracy. We performed an extensive study of existing confidence interval methods and compared their performance in terms of empirical coverage and width. We developed a bootstrap case cross-validation (BCCV) resampling scheme and defined several confidence interval methods using BCCV with and without bias-correction. The widely used approach of basing confidence intervals on an independent binomial assumption of the leave-one-out cross-validation errors results in serious under-coverage of the true prediction error. Two split-sample based methods previously proposed in the literature tend to give overly conservative confidence intervals. Using BCCV resampling, the percentile confidence interval method was also found to be overly conservative without bias-correction, while the bias corrected accelerated (BCa) interval method of Efron returns substantially anti-conservative confidence intervals. We propose a simple bias reduction on the BCCV percentile interval. The method provides mildly conservative inference under all circumstances studied and outperforms the other methods in microarray applications with small to moderate sample sizes. C1 [Jiang, Wenyu] Concordia Univ, Dept Math & Stat, Montreal, PQ H3G 1M8, Canada. [Varma, Sudhir] Natl Canc Inst, Genom & Bioinformat Grp, Mol Pharmacol Lab, Bethesda, MD 20892 USA. [Simon, Richard] Natl Canc Inst, Biomet Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Jiang, WY (reprint author), Concordia Univ, Dept Math & Stat, 1455 Maisonneuve Blvd W, Montreal, PQ H3G 1M8, Canada. EM wjiang@mathstat.concordia.ca; varmas@mail.nih.gov; rsimon@mail.nih.gov NR 20 TC 15 Z9 16 U1 0 U2 0 PU BERKELEY ELECTRONIC PRESS PI BERKELEY PA 2809 TELEGRAPH AVENUE, STE 202, BERKELEY, CA 94705 USA SN 1544-6115 J9 STAT APPL GENET MOL JI Stat. Appl. Genet. Mol. Biol. PY 2008 VL 7 IS 1 AR 8 PG 21 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 282KY UT WOS:000254567900005 ER PT J AU Hu, ZH Wang, NY AF Hu, Zonghui Wang, Naisyin TI Semiparametric latent covariate mixed-effects models with application to a colon carcinogenesis study SO STATISTICS AND ITS INTERFACE LA English DT Article DE Carcinogenesis; Consistency; Generalized estimating equation; Local linear smoothing; Mixed-effects model ID DNA ADDUCT LEVELS; LINEAR-MODELS; ERROR; APOPTOSIS AB We study a mixed-effects model in which the response and the main covariate are linked by position. While the covariate corresponding to the observed response is not directly observable, there exists a latent covariate process that represents the underlying positional features of the covariate. When the positional features and the underlying distributions are parametric, the expectation-maximization (EM) is the most commonly used procedure. Though without the parametric assumptions, the practical feasibility of a semiparametric EM algorithm and the corresponding inference procedures remain to be investigated. In this paper, we propose a semiparametric approach, and identify the conditions under which the semiparametric estimators share the same asymptotic properties as the unachievable estimators using the true values of the latent covariate; that is, the oracle property is achieved. We propose a Monte Carlo graphical evaluation tool to assess the adequacy of the sample size for achieving the oracle property. The semiparametric approach is later applied to data from a colon carcinogenesis study on the effects of cell DNA damage on the expression level of oncogene bcl-2. The graphical evaluation shows that, with moderate size of subunits, the numerical performance of the semiparametric estimator is very close to the asymptotic limit. It indicates that a complex EM-based implementation may at most achieve minimal improvement and is thus unnecessary. C1 [Hu, Zonghui] NIAID, NIH, Bethesda, MD 20817 USA. [Wang, Naisyin] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Hu, ZH (reprint author), NIAID, NIH, Bethesda, MD 20817 USA. EM huzo@niaid.nih.gov; nwang@stat.tamu.edu FU US National Cancer Institute [CA74552]; Texas AM Foundation FX This research was supported by a grant, CA74552, from the US National Cancer Institute. It was also partially supported by the Texas A&M Foundation LINK program. NR 19 TC 0 Z9 0 U1 0 U2 0 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 J9 STAT INTERFACE JI Stat. Interface PY 2008 VL 1 IS 1 BP 75 EP 86 PG 12 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA V13GG UT WOS:000207654700008 PM 20148130 ER PT S AU Jabbi, M Korf, J Ormel, J Kema, IP den Boer, JA AF Jabbi, Mbemba Korf, Jaalp Ormel, Johan Kema, Ido P. den Boer, Johan A. BE Kvetnansky, R Aguilera, G Goldstein, D Jezova, D Krizanova, O Sabban, EL Pacak, K TI Investigating the Molecular Basis of Major Depressive Disorder Etiology SO STRESS, NEUROTRANSMITTERS, AND HORMONES: NEUROENDOCRINE AND GENETIC MECHANISMS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 9th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 16-21, 2007 CL Bethesda, MD SP Inst Exptl Endocrinol, Ctr Excellence European Commiss, Slovak Acad Sci, Natl Inst Hlth DE stress; genes; monoamines; MDD; convergent ID CATECHOL-O-METHYLTRANSFERASE; CORTICOTROPIN-RELEASING HORMONE; NATIONAL COMORBIDITY SURVEY; PITUITARY-ADRENAL AXIS; STRESSFUL LIFE EVENTS; GENE-ENVIRONMENT INTERACTION; ANXIETY-LIKE BEHAVIOR; SECRETION IN-VITRO; SEROTONIN TRANSPORTER; MONOAMINE-OXIDASE AB Genes play a major role in behavioral adaptation to challenging environmental stimuli, but the complexity of their contribution remains unclear. There is growing evidence linking disease phenotypes with genes on the one hand, and the genesis of stress-related disorders like major depression, as a result of exposure to stressful environmental pathogens on the other. Here we illustrate the convergent role of monoaminergic genes in regulating the underlying biological mechanisms of stress and the emotions. By reviewing data that support a role of monoaminergic and other related genes in environmental adaptation, we conclude by advocating the use of convergent approaches in examining the genetic modulation of disease phenotypes. C1 [Kema, Ido P.] Univ Med Ctr Groningen, Dept Lab Med, Groningen, Netherlands. [Jabbi, Mbemba] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands. RP Jabbi, M (reprint author), NIMH IRP, Sect Integrat Neuroimaging, CBDB, NIH,DHHS, Bethesda, MD 20892 USA. EM jabbim@mail.nih.gov RI Ormel, Johan/C-6094-2013 FU Intramural NIH HHS [Z99 MH999999] NR 112 TC 14 Z9 14 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-692-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1148 BP 42 EP 56 DI 10.1196/annals.1410.018 PG 15 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIS00 UT WOS:000262398300003 PM 19120090 ER PT S AU Thorsell, A AF Thorsell, Annika BE Kvetnansky, R Aguilera, G Goldstein, D Jezova, D Krizanova, O Sabban, EL Pacak, K TI Central Neuropeptide Y in Anxiety- and Stress-related Behavior and in Ethanol Intake SO Stress, Neurotransmitters, and Hormones: Neuroendocrine and Genetic Mechanisms SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 16-21, 2007 CL Bethesda, MD SP Inst Exptl Endocrinol, Ctr Excellence European Commiss, Slovak Acad Sci, Natl Inst Hlth DE neuropeptide Y; animal model; anxiety; stress; Y1 receptor; alcohol ID RECEPTOR ANTAGONIST BIBP3226; MESSENGER-RNA EXPRESSION; ANXIOLYTIC-LIKE ACTION; ALCOHOL-PREFERRING P; INNATE DIFFERENCES; RESTRAINT STRESS; CENTRAL NUCLEUS; KNOCKOUT MICE; CONFLICT TEST; NPY AB One of the most profound properties of central neuropeptide Y (NPY) is its anxiolytic, or anti-anxiety, effect. This has been demonstrated repeatedly in a number of animal models. In addition, stressors affect NPY expression in the central nervous system, with acute and repeated (chronic) stress having differential effects. Here, a brief summary of some work performed in our laboratory is presented that supports a role for NPY in regulation of stress responses and behaviors. C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. RP Thorsell, A (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, Bldg 10-CRC Room 1-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM annika.thorsell@mail.nih.gov OI Thorsell, Annika/0000-0003-3535-3845 NR 41 TC 20 Z9 21 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-692-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1148 BP 136 EP 140 DI 10.1196/annals.1410.083 PG 5 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIS00 UT WOS:000262398300014 PM 19120101 ER PT S AU Goldstein, DS AF Goldstein, David S. BE Kvetnansky, R Aguilera, G Goldstein, D Jezova, D Krizanova, O Sabban, EL Pacak, K TI Computer Models of Stress, Allostasis, and Acute and Chronic Diseases SO Stress, Neurotransmitters, and Hormones: Neuroendocrine and Genetic Mechanisms SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 16-21, 2007 CL Bethesda, MD SP Inst Exptl Endocrinol, Ctr Excellence European Commiss, Slovak Acad Sci, Natl Inst Hlth DE stress; allostasis; catecholamines; homeostasis AB The past century has seen a profound shift in diseases of humankind. Acute, unifactorial diseases are being replaced increasingly by multifactorial disorders that arise from complex interactions among genes, environment, concurrent morbidities and treatments, and time. According to the concept of allostasis, there is no single, ideal set of steady-state conditions in life. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators-"homeostats." Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a set point for response leads to activation of effectors, reducing the discrepancy. "Allostatic load" refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of a home temperature control system, the temperature can be maintained at any of a variety of levels (allostatic states) by multiple means (effectors), regulated by a comparator thermostat (homeostat). Stress might exert adverse health consequences via allostatic load. This presentation describes models of homeostatic systems that incorporate negative feedback regulation, multiple effectors, effector sharing, environmental influences, intrinsic obsolescence, and destabilizing positive feedback loops. These models can be used to predict effects of environmental and genetic alterations on allostatic load and therefore on the development of multisystem disorders and failures. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr,MSC-1620,Bldg 10,Room 6N252, Bethesda, MD 20892 USA. EM goldstein@ninds.nih.gov FU Intramural NIH HHS [Z01 NS003034-01, Z01 NS003033-01] NR 3 TC 9 Z9 9 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-692-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1148 BP 223 EP 231 DI 10.1196/annals.1410.061 PG 9 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIS00 UT WOS:000262398300027 PM 19120114 ER PT S AU Ebert, SN Rong, Q Boe, S Pfeifer, K AF Ebert, Steven N. Rong, Qi Boe, Steve Pfeifer, Karl BE Kvetnansky, R Aguilera, G Goldstein, D Jezova, D Krizanova, O Sabban, EL Pacak, K TI Catecholamine-Synthesizing Cells in the Embryonic Mouse Heart SO STRESS, NEUROTRANSMITTERS, AND HORMONES: NEUROENDOCRINE AND GENETIC MECHANISMS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 9th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 16-21, 2007 CL Bethesda, MD SP Inst Exptl Endocrinol, Ctr Excellence European Commiss, Slovak Acad Sci, Natl Inst Hlth DE Pnmt; epinephrine; Cre-recombinase; progenitor cell; mouse; LAC-Z ID PHENYLETHANOLAMINE N-METHYLTRANSFERASE; RAT-HEART; FETAL DEVELOPMENT; ADRENERGIC CELLS; FORMING FIELD; EPINEPHRINE; PACEMAKING; MYOCARDIUM; EXPRESSION; REVEALS AB The heart is a primary source of epinephrine and norepinephrine during embryonic development, yet little is known about the cardiac cells that produce these catecholamine hormones. To identify when and where catecholamine-synthesizing cells are found in the embryonic heart, we developed a novel mouse genetic model by "knocking-in" the Cre-recombinase gene to the locus encoding for the epinephrine biosynthetic enzyme, phenylethanolamine n-methyltransferase. When crossed with ROSA26 reporter mice, the P-galactosidase gene is activated in adrenergic cells. A major advantage of this approach is that it allows detection of adrenergic cells and their progeny, regardless of whether the progeny cells retain an adrenergic phenotype or not. Our data show that adrenergic cells appear as early as embryonic day 8.5 and continue to accumulate in substantial numbers through birth in the mouse heart, where they appear to share common ancestry with myocardial lineages. Large numbers of atrial and especially ventricular myocytes appear to be derived from embryonic adrenergic cells in the heart. In addition, many of the pacemaking cells in the sinoatrial and atrioventricular nodes also appear to be derived from an adrenergic lineage. Thus, our results suggest that catecholamine-synthesizing cells serve as cardiomyocyte progenitors in the embryonic heart. C1 [Ebert, Steven N.] Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, Biomol Sci Ctr, Orlando, FL 32816 USA. [Rong, Qi; Boe, Steve; Pfeifer, Karl] NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD USA. RP Ebert, SN (reprint author), Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, Biomol Sci Ctr, 4000 Cent Florida Blvd, Orlando, FL 32816 USA. EM ebert@mail.ucf.edu OI Pfeifer, Karl/0000-0002-0254-682X FU NIH [HL78716]; Stem Cell Research Foundation; division of the American Cell Therapy Research Foundation; NICHD/NIH FX This work was supported by NIH Grant HL78716 (SNE), a grant from the Stem Cell Research Foundation, a division of the American Cell Therapy Research Foundation (SNE), and intramural funds from the NICHD/NIH (K.P). NR 22 TC 9 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-692-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1148 BP 317 EP 324 DI 10.1196/annals.1410.008 PG 8 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIS00 UT WOS:000262398300037 PM 19120124 ER PT S AU Chen, J Young, S Subburaju, S Sheppard, J Kiss, A Atkinson, H Wood, S Lightman, S Gal, CSL Aguilera, G AF Chen, Jun Young, Sharla Subburaju, Sivan Sheppard, Jack Kiss, Alexander Atkinson, Helen Wood, Susan Lightman, Stafford Gal, Claudine Serradeil-Le Aguilera, Greti BE Kvetnansky, R Aguilera, G Goldstein, D Jezova, D Krizanova, O Sabban, EL Pacak, K TI Vasopressin Does Not Mediate Hypersensitivity of the Hypothalamic Pituitary Adrenal Axis during Chronic Stress SO Stress, Neurotransmitters, and Hormones: Neuroendocrine and Genetic Mechanisms SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 16-21, 2007 CL Bethesda, MD SP Inst Exptl Endocrinol, Ctr Excellence European Commiss, Slovak Acad Sci, Natl Inst Hlth DE stress; vasopressin; HPA axis; vasopressin antagonists; vasopressin V1b receptor ID CORTICOTROPIN-RELEASING HORMONE; V-1B RECEPTOR ANTAGONIST; RAT ANTERIOR-PITUITARY; ARGININE-VASOPRESSIN; REPEATED RESTRAINT; IMMOBILIZATION STRESS; RESPONSES; ADRENOCORTICOTROPIN; SECRETION; CORTICOSTERONE AB The hypothesis that vasopressin (VP) becomes the main mediator of pituitary corticotroph responsiveness during chronic hypothalamic pituitary adrenal (HPA) axis activation was tested by examining the effect of pharmacologic VP receptor blockade on the adrenocorticotropic hormone (ACTH) and corticosterone responses of 14-day repeatedly restrained rats. In spite of the increased vasopressinergic activity, repeatedly restrained rats showed lower ACTH and corticosterone responses to 10 min white noise compared with handled controls. These responses were unchanged by injection of the nonpeptide-selective V1b receptor antagonist SSR149415 i.v., 1 h before noise application. In contrast to noise stress, plasma ACTH responses to i.p. hypertonic saline injection were enhanced in the repeatedly restrained rats compared with handled controls, but responses were also unaffected by SSR149415 administered orally, daily 1 h before restraint. Since SSR149415 effectiveness was low, we used minipump infusion of the peptide V1 receptor antagonist, dGly[Phaa1,D-tyr(et), Lys, Arg]VP (V1-Ant) for 14 days, which effectively blocked ACTH responses to exogenous VP Chronic V1-Ant infusion reduced plasma ACTH responses to i.p. hypertonic saline in handled controls but not in repeatedly restrained rats. These data suggest that the increased vasopressinergic activity characteristic of chronic stress plays roles other than mediating the hypersensitivity of the HPA axis to a novel stress. C1 [Aguilera, Greti] NICHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,CRC, Bethesda, MD 20892 USA. [Kiss, Alexander] Slovak Acad Sci, Inst Expt Endocrinol, Bratislava, Slovakia. [Atkinson, Helen; Wood, Susan; Lightman, Stafford] Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Dept Med, Bristol, Avon, England. [Gal, Claudine Serradeil-Le] Sanofi Aventis, Exploratory Res Dept, Toulouse, France. RP Aguilera, G (reprint author), NICHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH,CRC, Rm 1E-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM Greti_Aguilera@uih.gov; Greti_Aguilera@uih.gov RI Atkinson, Helen/B-9246-2015 OI Atkinson, Helen/0000-0002-2172-3780 FU National Institute of Child Health and Human Development, NIH FX This work was supported by the Intramural Research Program of the National Institute of Child Health and Human Development, NIH. NR 34 TC 24 Z9 25 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-692-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1148 BP 349 EP 359 DI 10.1196/annals.1410.037 PG 11 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIS00 UT WOS:000262398300041 PM 19120128 ER PT S AU Pavel, J Benicky, J Murakami, Y Sanchez-Lemus, E Saavedra, JM AF Pavel, Jaroslav Benicky, Julius Murakami, Yuki Sanchez-Lemus, Enrique Saavedra, Juan M. BE Kvetnansky, R Aguilera, G Goldstein, D Jezova, D Krizanova, O Sabban, EL Pacak, K TI Peripherally Administered Angiotensin II AT(1) Receptor Antagonists Are Anti-stress Compounds in Vivo SO Stress, Neurotransmitters, and Hormones: Neuroendocrine and Genetic Mechanisms SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 16-21, 2007 CL Bethesda, MD SP Inst Exptl Endocrinol, Ctr Excellence European Commiss, Slovak Acad Sci, Natl Inst Hlth DE renin angiotensin system; inflammation; brain; gastric ulcers; corticotropin-releasing hormone; GABA(A); sympathetic system ID RAT-BRAIN; PARAVENTRICULAR NUCLEUS; ISOLATION STRESS; BENZODIAZEPINE BINDING; AT(2) RECEPTORS; PITUITARY; EXPRESSION; SUBTYPES; HORMONE; CANDESARTAN AB Angiotensin II AT(1) receptor blockers (ARBs) are commonly used in the clinical treatment of hypertension. Subcutaneous or oral administration of the ARB candesartan inhibits brain as well as peripheral AT(1) receptors, indicating transport across the blood-brain barrier. Pretreatment with candesartan profoundly modifies the response to stress. The ARB prevents the peripheral and central sympathetic activation characteristic of isolation stress and abolishes the activation of the hypothalamic-pituitary-adrenal axis during isolation. In addition, candesartan prevents the isolation-induced decrease in cortical corticotropin-releasing factor 1 and benzodiazepine receptors induced by isolation. When administered before cold-restraint stress, candesartan totally prevents the production of gastric ulcerations. This preventive effect of candesartan is the consequence of profound anti-inflammatory effects, reduction of sympathetic stimulation, and preservation of blood flow to the gastric mucosa. The ARB does not reduce the hypothalamic-pituitary-adrenal axis stimulation during cold restraint. Preservation of the effects of endogenous glucocorticoids is essential for protection of the gastric mucosa during cold restraint. Administration of the ARB to nonstressed rats decreases anxiety in the elevated plus-maze. Our results demonstrate that Angiotensin II, through AT, receptor stimulation, is a major stress hormone, and that ARBs, in addition to their antihypertensive effects, may be considered for the treatment of stress-related disorders. C1 [Pavel, Jaroslav; Benicky, Julius; Murakami, Yuki; Sanchez-Lemus, Enrique; Saavedra, Juan M.] NIH, Pharmacol Sect, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIH, Pharmacol Sect, 10 Ctr Dr,Room 2D 57, Bethesda, MD 20892 USA. EM saavedrj@mail.nih.gov FU Intramural NIH HHS [Z01 MH002762-11, Z99 MH999999] NR 37 TC 30 Z9 30 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-692-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1148 BP 360 EP 366 DI 10.1196/annals.1410.006 PG 7 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIS00 UT WOS:000262398300042 PM 19120129 ER PT S AU Kantorovich, V Eisenhofer, G Pacak, K AF Kantorovich, Vitaly Eisenhofer, Graeme Pacak, Karel BE Kvetnansky, R Aguilera, G Goldstein, D Jezova, D Krizanova, O Sabban, EL Pacak, K TI Pheochromocytoma An Endocrine Stress Mimicking Disorder SO Stress, Neurotransmitters, and Hormones: Neuroendocrine and Genetic Mechanisms SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 16-21, 2007 CL Bethesda, MD SP Inst Exptl Endocrinol, Ctr Excellence European Commiss, Slovak Acad Sci, Natl Inst Hlth DE pheochromocytoma; stress; general adaptation syndrome; adrenoceptors; catecholamines; hypothalamic-pituitary-adrenocortical axis; glucocorticoids ID BETA-ADRENERGIC RECEPTORS; CATECHOLAMINE CARDIOMYOPATHY; DESENSITIZATION; LYMPHOCYTES; ADRENALINE; FEATURES; FAILURE; LESIONS AB A pheochromocytoma is an endocrine tumor that can uniquely mimic numerous stress-associated disorders, with variations in clinical manifestations resulting from different patterns of catecholamine secretion and actions of released catecholamines on physiological systems. C1 [Pacak, Karel] NICHHD, NIH, Sec Med Neuroendocrinol, Reprod & Adult Endocrinol Program, Bethesda, MD 20892 USA. [Kantorovich, Vitaly] Univ Arkansas Med Sci, Div Endocrinol, Little Rock, AR 72205 USA. [Eisenhofer, Graeme] Univ Dresden, Dept Med, Dept Clin Chem & Lab Med, Dresden, Germany. RP Kantorovich, V (reprint author), NICHHD, NIH, Sec Med Neuroendocrinol, Reprod & Adult Endocrinol Program, Bldg 10,CRC,Room 1E-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.mih.gov FU National institute of Child Health and Human Development FX This work was supported in part by the Intramural Research Program of the National institute of Child Health and Human Development. NR 38 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-692-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1148 BP 462 EP 468 DI 10.1196/annals.1410.081 PG 7 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIS00 UT WOS:000262398300055 PM 19120142 ER PT S AU Eisenhofer, G Sharabi, Y Pacak, K AF Eisenhofer, Graeme Sharabi, Yehonatan Pacak, Karel BE Kvetnansky, R Aguilera, G Goldstein, D Jezova, D Krizanova, O Sabban, EL Pacak, K TI Unexplained Symptomatic Paroxysmal Hypertension in Pseudopheochromocytoma A Stress Response Disorder? SO STRESS, NEUROTRANSMITTERS, AND HORMONES: NEUROENDOCRINE AND GENETIC MECHANISMS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 9th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 16-21, 2007 CL Bethesda, MD SP Inst Exptl Endocrinol, Ctr Excellence European Commiss, Slovak Acad Sci, Natl Inst Hlth DE pheochromocytoma; catecholamines; sympathetic nervous system; adrenal medulla ID ADRENAL-MEDULLARY HYPERPLASIA; OBSTRUCTIVE SLEEP-APNEA; RESISTANT HYPERTENSION; PARKINSONS-DISEASE; SURGICAL TECHNIQUE; FEASIBILITY TRIAL; PANIC DISORDER; PAGES-SYNDROME; PHEOCHROMOCYTOMA; PSEUDOPHAEOCHROMOCYTOMA AB Among overall numbers of patients tested for pheochromocytoma, less than 2% harbor the tumor. Among the rest, there is often no satisfactory explanation for the signs and symptoms leading to suspicion of pheochromocytoma. This group includes patients with severe symptomatic paroxysmal hypertension, often referred to as pseudopheochromocytoma, a condition that can be debilitating for patients and perplexing for clinicians. Similar to patients with the real tumor, patients with pseudopheochromocytomacan be misdiagnosed with panic disorder. However, pseudopheochromocytoma is characterized by an absence of panic or emotional distress preceding the onset of hypertension and symptoms of catecholamine excess. Because the clinical manifestations of pseudopheochromocytoma are similar, if not identical, to those due to excess circulating catecholamines in patients with the tumor, the most attractive explanation for the disorder is that it involves altered function of the autonomic nervous system. In line with this hypothesis, recent findings suggest that enhanced adrenal release of epinephrine and exaggerated cardiovascular responsiveness to catecholamines both contribute to the paroxysmal hypertension and symptoms of catecholamine excess in pseudopheochromocytoma. From this pattern, one would predict that therapeutic interventions that inhibit adrenal secretion of epinephrine or block adrenoceptor-mediated responses to catecholamines might provide a logical approach to therapy. C1 [Eisenhofer, Graeme] Univ Dresden, Dept Med, Div Clin Neurochem, D-01307 Dresden, Germany. [Eisenhofer, Graeme] Univ Dresden, Dept Clin Chem & Lab Med, D-01307 Dresden, Germany. [Sharabi, Yehonatan] Tel Aviv Univ, Chaim Sheba Med Ctr, Hypertens Unit, IL-69978 Tel Aviv, Israel. [Pacak, Karel] NICHHD, NIH, Reprod & Adult Endocrinol Program, Bethesda, MD 20892 USA. RP Eisenhofer, G (reprint author), Univ Dresden, Dept Med, Div Clin Neurochem, Fetscherstr 74, D-01307 Dresden, Germany. EM graeme.eisenhofer@uniklinikum-dresden.de NR 46 TC 5 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 978-1-57331-692-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1148 BP 469 EP 478 DI 10.1196/annals.1410.019 PG 10 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIS00 UT WOS:000262398300056 PM 19120143 ER PT S AU Imrich, R Eldadah, BA Bentho, O Pechnik, S Sharabi, Y Holmes, C Goldstein, DS AF Imrich, Richard Eldadah, Basil A. Bentho, Oladi Pechnik, Sandra Sharabi, Yehonatan Holmes, Courtney Goldstein, David S. BE Kvetnansky, R Aguilera, G Goldstein, D Jezova, D Krizanova, O Sabban, EL Pacak, K TI Attenuated Pre-ejection Period Response to Tyramine in Patients with Cardiac Sympathetic Denervation SO Stress, Neurotransmitters, and Hormones: Neuroendocrine and Genetic Mechanisms SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 9th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 16-21, 2007 CL Bethesda, MD SP Inst Exptl Endocrinol, Ctr Excellence European Commiss, Slovak Acad Sci, Natl Inst Hlth DE Parkinson disease; pure autonomic failure; multiple system atrophy; sympathetic denervation; pre-ejection period ID PARKINSONS-DISEASE AB Stress is a well-known factor affecting cardiac contractility through the cardiac sympathetic nerves. A positive inotropic effect of the cardiac sympathetic nerves on the myocardium is reflected by pre-ejection period (PEP) shortening. Patients with Parkinson disease (PD) and neurogenic orthostatic hypotension (NOH) (PD + NOH) or with pure autonomic failure (PAF) have markedly decreased myocardial 6-[(18)F]Fluorodopamine-derived radioactivity, reflecting cardiac sympathetic denervation. The functional effects of the cardiac sympathetic denervation have been unknown. We measured PEP and heart rate-corrected PEP (PEPI) responses to i.v. tyramine: (1 mg/min) in 13 patients (9 PD + NOH and 4 PAF) with low 6-[(18)F]Fluorodopamine-derived radioactivity and in subjects with normal radioactivity (15 multiple system atrophy with NOS patients (MSA + NOS). Baseline PEP and PEPI did not differ between the groups. By 10 min alter initiation of tyramine infusion, PEP and PEPI were significantly lower (P < 0.01) in MSA + NOS, compared to base line, whereas PEP and PEPI remained unchanged in the PD + NOH/PAF group. The PEP and PEPI decrease was larger in the MSA + NOS group than in the PD + NOH/PAF group (P < 0.05). One of the functional consequences of cardiac sympathetic denervation is failure to increase contractility in response to stimuli that depend on endogenous norepinephrine release. C1 [Imrich, Richard; Eldadah, Basil A.; Bentho, Oladi; Pechnik, Sandra; Sharabi, Yehonatan; Holmes, Courtney; Goldstein, David S.] Natl Inst Neurol Disorders & Stroke, NIH, Clin Neurocardiol Sect, Bethesda, MD USA. RP Imrich, R (reprint author), Ctr Mol Med, Vlarska 7, Bratislava 83101, Slovakia. EM richard.imrich@savba.sk FU NIH FX The research reported here was supported by the intramural research program of the NIH. NR 9 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-692-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1148 BP 486 EP 489 DI 10.1196/annals.1410.066 PG 4 WC Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Physiology SC Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIS00 UT WOS:000262398300058 PM 19120145 ER PT J AU Bregonzio, C Seltzer, A Armando, I Pavel, J Saavedra, JM AF Bregonzio, C. Seltzer, A. Armando, I. Pavel, J. Saavedra, J. M. TI Angiotensin II AT(1) receptor blockade selectively enhances brain AT(2) receptor expression, and abolishes the cold-restraint stress-induced increase in tyrosine hydroxylase mRNA in the locus coeruleus of spontaneously hypertensive rats SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Article DE Angiotensin II receptors; brain; central sympathetic system; locus coeruleus; renin angiotensin system; stress ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; IMMOBILIZATION STRESS; ANTAGONIST PREVENTS; SUBFORNICAL ORGAN; BINDING-SITES; PITUITARY; NEURONS; SUBTYPES; GENE; VASOPRESSIN AB Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated orally for 14 days with the AT(1) receptor antagonist candesartan before submission to 2 h of cold-restraint stress. In non-treated rats, stress decreased AT(1) receptor binding in the median eminence and basolateral amygdala, increased AT(2) receptor binding in the medial subnucleus of the inferior olive, decreased AT(2) binding in the ventrolateral thalamic nucleus and increased tyrosine hydroxylase mRNA level in the locus coeruleus. In non-stressed rats, AT(1) receptor blockade reduced AT(1) receptor binding in all areas studied and enhanced AT(2) receptor binding in the medial subnucleus of the inferior olive. Candesartan pretreatment produced a similar decrease in brain AT(1) binding after stress, and prevented the stress-induced AT(2) receptor binding decrease in the ventrolateral thalamic nucleus. In the locus coeruleus and adrenal medulla, AT(1) blockade abolished the stress-induced increase in tyrosine hydroxylase mRNA level. Our results demonstrate that oral administration of candesartan effectively blocked brain AT(1) receptors, selectively increased central AT(2) receptor expression and prevented the stress-induced central stimulation of tyrosine hydroxylase transcription. The present results support a role of brain AT(1) and AT(2) receptors in the regulation of the stress response, and the hypothesis that AT(1) receptor antagonists may be considered as potential therapeutic compounds in stress related disorders in addition to their anti-hypertensive properties. C1 [Saavedra, J. M.] NIMH, Pharmacol Sect, DIRP, NIH,DHHS, Bethesda, MD 20892 USA. [Bregonzio, C.; Seltzer, A.; Armando, I.] Natl Univ Cordoba, Fac Chem Sci, Dept Pharmacol, Cordoba, Argentina. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, DIRP, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. EM Saavedrj@mail.nih.gov FU Division of Intramural Research Programs; National Institute of Mental Health; National Institutes of Health; Department of Health and Human Services, USA FX This study was supported by the Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, USA. NR 54 TC 24 Z9 24 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1025-3890 J9 STRESS JI Stress PY 2008 VL 11 IS 6 BP 457 EP 466 DI 10.1080/10253890801892040 PG 10 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA 389QN UT WOS:000262109700005 PM 18609298 ER PT J AU Milner, R Hung, S Wang, X Berg, GI Spatz, M del Zoppo, GJ AF Milner, Richard Hung, Stephanie Wang, Xiaoyun Berg, Greta I. Spatz, Maria del Zoppo, Gregory J. TI Responses of endothelial cell and astrocyte matrix-integrin receptors to ischemia mimic those observed in the neurovascular unit SO STROKE LA English DT Article DE astrocytes; endothelial cells; integrins; ischemic stroke; matrix ID BLOOD-BRAIN-BARRIER; FOCAL CEREBRAL-ISCHEMIA; EXTRACELLULAR-MATRIX; ADHESION MOLECULES; EXPRESSION; DIFFERENTIATION; LAMININ; ALPHA; RAT; ISCHEMIA/REPERFUSION AB Background and Purpose-Apposition of endothelial cells and astrocyte foot processes to the basal lamina matrix is postulated to underlie the cerebral microvessel permeability barrier. Focal cerebral ischemia induces rapid loss of select matrix-binding integrins from both cell compartments in the nonhuman primate. This study is the first to examine the conditions underlying integrin loss from these cell-types during ischemia in vitro and their relation to the changes in vivo. Methods-The impact of normoxia or standardized oxygen-glucose deprivation on integrin expression by murine primary cerebral endothelial cells and astrocytes grown on matrix substrates ( collagen IV, laminin, and perlecan) of the basal lamina were quantitatively assessed by flow cytometry. Results-Endothelial cell expression of the beta 1 and alpha 5 subunits significantly increased on all matrix ligands, whereas astrocytes displayed modest significant decreases in alpha 5 and alpha 6 subunits. Oxygen-glucose deprivation produced a further significant increase in subunit beta 1 expression by both cell types, but a clear decrease in both alpha 1 and alpha 6 subunits by murine astrocytes. Conclusions-Ischemia in vitro significantly increased endothelial cell beta 1 expression, which is consistent with the increase in beta 1 transcription by microvessels peripheral to the ischemic core. The loss of alpha 1 and alpha 6 integrins from murine astrocytes is identical to that seen in the nonhuman primate in vivo. These findings establish both isolated murine cerebral endothelial cells and astrocytes as potential integrin response cognates of microvascular cells of the neurovascular unit in primates, and allow determination of the mechanisms of their changes to ischemia. C1 [del Zoppo, Gregory J.] Univ Washington, Harborview Med Ctr, Dept Med Neurol, Seattle, WA 98104 USA. [Milner, Richard; Hung, Stephanie; Wang, Xiaoyun; Berg, Greta I.; del Zoppo, Gregory J.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA. [del Zoppo, Gregory J.] Univ Washington, Dept Med Neurol, Seattle, WA 98195 USA. [Spatz, Maria] Natl Inst Neurol Disorders & Stroke, Stroke Branch, Bethesda, MD USA. RP del Zoppo, GJ (reprint author), Univ Washington, Harborview Med Ctr, Dept Med Neurol, 325 9Th Ave, Seattle, WA 98104 USA. EM grgdlzop@u.washington.edu FU NINDS NIH HHS [R01 NS026945, R01 NS053716, R01 NS053716-04, R37 NS038710, R37 NS038710-08] NR 40 TC 61 Z9 62 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2008 VL 39 IS 1 BP 191 EP 197 DI 10.1161/STROKEAHA.107.486134 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 245HB UT WOS:000251924600032 PM 18032737 ER PT J AU Lengyel, JS Stott, KM Wu, XW Brooks, BR Balbo, A Schuck, P Perham, RN Subramaniam, S Milne, JLS AF Lengyel, Jeffrey S. Stott, Katherine M. Wu, Xiongwu Brooks, Bernard R. Balbo, Andrea Schuck, Peter Perham, Richard N. Subramaniam, Sriram Milne, Jacqueline L. S. TI Extended polypeptide linkers establish the spatial architecture of a pyruvate dehydrogenase multienzyme complex SO STRUCTURE LA English DT Article ID SUBUNIT-BINDING DOMAIN; NMR CHEMICAL-SHIFTS; BACILLUS-STEAROTHERMOPHILUS; ESCHERICHIA-COLI; CRYOELECTRON MICROSCOPY; E1 COMPONENT; E3 COMPONENTS; DIHYDROLIPOAMIDE ACETYLTRANSFERASE; PROTEIN DOMAIN; LIPOYL DOMAIN AB Icosahedral pyruvate dehydrogenase (PDH) enzyme complexes are molecular machines consisting of a central E2 core decorated by a shell of peripheral enzymes (E1 and E3) found localized at a distance of similar to 75-90 angstrom from the core. Using a combination of biochemical, biophysical, and cryo-electron microscopic techniques, we show here that the gap between the E2 core and the shell of peripheral enzymes is maintained by the flexible but extended conformation adopted by 60 linker polypeptides that radiate outwards from the inner E2 core, irrespective of the E1 or E3 occupancy. The constancy of the gap is thus not due to protein-protein interactions in the outer protein shell. The extended nature of the E2 inner-linker regions thereby creates the restricted annular space in which the lipoyl domains of E2 that carry catalytic intermediates shuttle between E1, E2, and E3 active sites, while their conformational flexibility facilitates productive encounters. C1 [Lengyel, Jeffrey S.; Subramaniam, Sriram; Milne, Jacqueline L. S.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Lengyel, Jeffrey S.; Stott, Katherine M.; Perham, Richard N.] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England. [Wu, Xiongwu; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Balbo, Andrea; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Milne, JLS (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM jmilne@nih.gov OI Schuck, Peter/0000-0002-8859-6966 NR 60 TC 11 Z9 12 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD JAN PY 2008 VL 16 IS 1 BP 93 EP 103 DI 10.1016/j.str.2007.10.017 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 250FZ UT WOS:000252286700015 PM 18184587 ER PT J AU Khalsa, JH Treisman, G McCance-Katz, E Tedaldi, E AF Khalsa, Jag H. Treisman, Glenn McCance-Katz, Elinore Tedaldi, Ellen TI Medical Consequences of Drug Abuse and Co-Occurring Infections: Research at the National Institute on Drug Abuse SO SUBSTANCE ABUSE LA English DT Article DE Medical consequences; drug abuse; infections AB Substance abuse still remains one of the major problems in the world today, with millions of people abusing legal and illegal drugs. In addition, a billion people may also be infected with one or more infections. Both drugs of abuse and infections are associated with enormous burden of social, economic, and health consequences. This article briefly discusses a few medical consequences of drugs of abuse and infections such as human immunodeficiency virus, hepatitis C virus, psychiatric complications in hepatitis C infection, pharmacokinetic drug-drug interactions among medications used in the treatment of addiction and infections, and new drugs in development for the treatment of infections. Research is encouraged to study interactions between infections, drugs of abuse, and underlying pathophysiologic and molecular/genetic mechanisms of these interactions. C1 [Khalsa, Jag H.] Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. [Treisman, Glenn] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [McCance-Katz, Elinore] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tedaldi, Ellen] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. RP Khalsa, JH (reprint author), Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Room 4137, Bethesda, MD 20892 USA. EM jk98p@nih.gov RI Reis, Aline/G-9573-2012 FU Intramural NIH HHS [Z99 DA999999] NR 76 TC 17 Z9 18 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2008 VL 29 IS 3 BP 5 EP 16 DI 10.1080/08897070802218661 PG 12 WC Substance Abuse SC Substance Abuse GA V14AX UT WOS:000207708400002 PM 19042203 ER PT J AU Elkashef, A Vocci, F Huestis, M Haney, M Budney, A Gruber, A El-Guebaly, N AF Elkashef, Ahmed Vocci, Frank Huestis, Marilyn Haney, Margaret Budney, Alan Gruber, Amanda el-Guebaly, Nady TI Marijuana Neurobiology and Treatment SO SUBSTANCE ABUSE LA English DT Article DE Marijuana; behavioral; pharmacotherapy; neurobiology AB Marijuana is the number one illicit drug of abuse worldwide and a major public health problem, especially in the younger population. The objective of this article is to update and review the state of the science and treatments available for marijuana dependence based on a pre-meeting workshop that was presented at ISAM 2006. At the workshop, several papers were presented addressing the neurobiology and pharmacology of marijuana and treatment approaches, both psychotherapy and medications, for marijuana withdrawal. Medicolegal and ethical issues concerning marijuana medical use were also discussed. Concise summaries of these presentations are incorporated in this article, which is meant to be an updated review of the state of the science. Major advances have been made in understanding the underpinning of marijuana dependence and the role of the CNS cannabinoid system, which is a major area for targeting medications to treat marijuana withdrawal and dependence, as well as other addictions. Behavioral therapies are efficacious for facilitating abstinence from marijuana. Nefazadone, Marinol, and buspirone are showing early positive signals for efficacy in ameliorating marijuana withdrawal symptoms. Effective psychotherapeutic approaches are available and promising medications studies need to be confirmed in outpatient trials. The next few years looking promising for translational research efforts to make treatment widely accessible to patients with marijuana dependence. C1 [Elkashef, Ahmed] Natl Inst Drug Abuse, Clin Med Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Vocci, Frank] Natl Inst Drug Abuse, Div Treatment Res & Dev, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Huestis, Marilyn] NIDA IRP, Baltimore, MD 21224 USA. [Haney, Margaret] Columbia Univ, Dept Psychiat, NYSPI, New York, NY 10032 USA. [Budney, Alan] Univ Arkansas Med Sci, Addict Res Ctr, Little Rock, AR 72206 USA. [Gruber, Amanda] McLean Hosp, Belmont, MA 02478 USA. [el-Guebaly, Nady] Foothills Prov Gen Hosp, Addict Ctr, Calgary, AB T2N 2T9, Canada. RP Elkashef, A (reprint author), Natl Inst Drug Abuse, Clin Med Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH,Dept Hlth & Human Serv, 6001 Execut Blvd,Room 4151, Bethesda, MD 20892 USA. EM ae8a@nih.gov FU Intramural NIH HHS [NIH0010134921]; PHS HHS [NIH0010134921] NR 68 TC 36 Z9 39 U1 11 U2 22 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2008 VL 29 IS 3 BP 17 EP 29 DI 10.1080/08897070802218166 PG 13 WC Substance Abuse SC Substance Abuse GA V14AX UT WOS:000207708400003 PM 19042204 ER PT J AU Elkashef, A Vocci, F Hanson, G White, J Wickes, W Tiihonen, J AF Elkashef, Ahmed Vocci, Frank Hanson, Glen White, Jason Wickes, Wendy Tiihonen, Jari TI Pharmacotherapy of Methamphetamine Addiction: An Update SO SUBSTANCE ABUSE LA English DT Article DE Methamphetamine; pharmacotherapy; bupropion; aripiprazole; methylphenidate; D-amphetamine AB Methamphetamine dependence is a serious public health problem worldwide for which there are no approved pharmacological treatments. Psychotherapy is still the mainstay of treatment; however, relapse rates are high. The search for effective pharmacological treatment has intensified in the last decade. This review will highlight progress in pharmacological interventions to treat methamphetamine dependence as well as explore new pharmacological targets. Published data from clinical trials for stimulant addiction were searched using PubMed and summarized, as well as highlights from a recent symposium on methamphetamine pharmacotherapy presented at the ISAM 2006 meeting, including interim analysis data from an ongoing D-amphetamine study in Australia. Early pilot data are encouraging for administering D-amphetamine and methylphenidate as treatment for heavy amphetamine users. Abilify at 15 mg/day dose increased amphetamine use in an outpatient pilot study. Sertraline, ondansetron, baclofen, tyrosine, and imipramine were ineffective in proof-of-concept studies. Development of pharmacotherapy for methamphetamine dependence is still in an early stage. Data suggesting D-amphetamine and methylphenidate as effective pharmacotherapy for methamphetamine addiction will need to be confirmed by larger trials. Preclinical data suggest that use of GVG, CB1 antagonist, and lobeline are also promising therapeutic strategies. C1 [Elkashef, Ahmed] Natl Inst Drug Abuse, Clin Med Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Vocci, Frank] Natl Inst Drug Abuse, Div Treatment Res & Dev, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hanson, Glen] Univ Utah, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA. [White, Jason; Wickes, Wendy] Univ Adelaide, Discipline Pharmacol, Pharmacotherapies Res Unit, Drug & Alcohol Serv S Australia, Adelaide, SA 5005, Australia. [Tiihonen, Jari] Univ Kuopio, Dept Forens Psychiat, Niuvanniemi Hosp, FI-70240 Kuopio, Finland. RP Elkashef, A (reprint author), Natl Inst Drug Abuse, Clin Med Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH,Dept Hlth & Human Serv, 6001 Execut Blvd,Room 4151, Bethesda, MD 20892 USA. EM ae8a@nih.gov RI White, Jason /A-2795-2011; Tiihonen, Jari/G-3078-2012 OI White, Jason /0000-0001-6750-1078; Tiihonen, Jari/0000-0002-0400-6798 FU Intramural NIH HHS [NIH0010134921]; PHS HHS [NIH0010134921] NR 99 TC 63 Z9 65 U1 2 U2 14 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 J9 SUBST ABUS JI Subst. Abus. PY 2008 VL 29 IS 3 BP 31 EP 49 DI 10.1080/08897070802218554 PG 19 WC Substance Abuse SC Substance Abuse GA V14AX UT WOS:000207708400004 PM 19042205 ER PT J AU Riggs, P Levin, F Green, AI Vocci, F AF Riggs, Paula Levin, Frances Green, Alan I. Vocci, Frank TI Comorbid Psychiatric and Substance Abuse Disorders: Recent Treatment Research SO SUBSTANCE ABUSE LA English DT Article DE Adolescence; comorbidity; depression; attention deficit hyperactivity disorder; schizophrenia AB Psychiatric comorbidity is defined as the co-occurrence of a psychiatric disorder in a patient with a substance use disorder. Psychiatric disorders in substance abuse patients can antedate the substance use disorder or be a consequence of the substance abuse. There is emerging evidence that drug use in adolescence may alter the onset of certain psychiatric disorders in vulnerable individuals. Patients with concurrent comorbid disorders present special challenges for the substance abuse treatment system in terms of diagnosis and management because each disorder has the capability of exacerbating the other. This manuscript is a summary of an ISAM symposium that featured three speakers who discussed the following topics: 1. Etiology and treatment of comorbid psychiatric and substance use disorders in adolescents; 2. Treatment of ADHD and substance use disorders in adults; 3. Effects of substance abuse on the onset, severity, and treatment of schizophrenia. Recommendations for further research will be presented. C1 [Vocci, Frank] Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Riggs, Paula] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80224 USA. [Levin, Frances] Columbia Univ, Ctr Med, Dept Psychiat, New York State Psychiat Inst,Div Subst Abuse, New York, NY 10032 USA. [Green, Alan I.] Dartmouth Med Sch, Dept Psychiat, Lebanon, NH 03756 USA. RP Vocci, F (reprint author), Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv, 6001 Execut Blvd,Room 4133, Bethesda, MD 20892 USA. EM fv6k@nih.gov FU NIH [DA-13196, AA-014644, MH-62197, R21 DA-019215, DA K0200465]; Eli Lilly; Janssen; Bristol Myers; Forest; AstraZeneca; NIDA [R01 DA 13176, U10-DA-1-3716] FX Dr. Green is supported in part by NIH grants DA-13196, AA-014644, MH-62197, and R21 DA-019215. Dr. Green reports grant support, honoraria, or advisory board service for Eli Lilly, Janssen, Bristol Myers, Forest, and AstraZeneca. Dr. Levin is supported in part by NIH grant DA K0200465. Dr. Riggs is supported by NIDA R01 DA 13176 and NIDA U10-DA-1-3716 and also receives honoraria from Shire as a consultant and advisory board member. NR 80 TC 14 Z9 15 U1 1 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0889-7077 EI 1547-0164 J9 SUBST ABUS JI Subst. Abus. PY 2008 VL 29 IS 3 BP 51 EP 63 DI 10.1080/08897070802218794 PG 13 WC Substance Abuse SC Substance Abuse GA V14AX UT WOS:000207708400005 PM 19042206 ER PT J AU Delany, P Shields, JJ Willenbring, ML Huebner, RB AF Delany, Peter J. Shields, Joseph J. Willenbring, Mark L. Huebner, Robert B. TI Expanding the Role of Health Services Research as a Tool to Reduce the Public Health Burden of Alcohol Use Disorders SO SUBSTANCE USE & MISUSE LA English DT Article DE health services; alcohol user treatment; alcohol diagnosis; context of treatment ID NATIONAL EPIDEMIOLOGIC SURVEY; GENERAL-POPULATION SAMPLE; SUBSTANCE USE DISORDERS; PRIMARY-CARE SETTINGS; RISK BEHAVIORS; UNITED-STATES; HIV-INFECTION; ADDICTION TREATMENT; BRIEF INTERVENTION; MENTAL-DISORDERS AB The public and private cost of heavy alcohol use1 is estimated to be more than 187 billion in lost productivity, health care and criminal justice expenditures, and other costs. This does not include the emotional and psychological costs to family, friends, and the community. Investments by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) have led to a number of important advances in pharmacological and behavioral treatments for alcohol disorders. Yet, there continues to be a significant gap between research findings and progress in community-based care. Additionally, limited capacity, a lack of acknowledged standards, and a separation between the specialty substance use treatment sector and general medical practice contribute to this gap. As part of its ongoing efforts to encourage translation from clinical research to practice, NIAAA undertook a review of its alcohol related health services research program for the purpose of creating a vision for the next 10 yr that is sensitive to the changing needs of both the clinical and research communities. Central to the development of a new research agenda is a reconceptualization of alcohol use and misuse along a continuum that takes into account quantity and frequency of use as well as the consequences from heavy use and misuse of alcohol. This public health approach recommends a number of high priority areas to expand and improve the system of care for heavy alcohol users who may be at-risk or who may have developed an alcohol use disorder. These recommendations include research on dissemination and implementation of evidence-based practices, and improving access and utilization to care for individuals who are heavy users. The paper concludes by outlining some of the steps taken by NIAAA to further the continuing development of alcohol health services research. C1 [Delany, Peter J.] Subst Abuse & Mental Hlth Serv Adm, Off Appl Studies, Rockville, MD 20857 USA. [Shields, Joseph J.] Catholic Univ Amer, Washington, DC 20064 USA. [Shields, Joseph J.; Willenbring, Mark L.; Huebner, Robert B.] NIAAA, Rockville, MD 20852 USA. RP Delany, P (reprint author), Subst Abuse & Mental Hlth Serv Adm, Off Appl Studies, 1 Choke Cherry Rd, Rockville, MD 20857 USA. EM Peter.Delany@samhsa.hhs.gov NR 64 TC 2 Z9 2 U1 5 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2008 VL 43 IS 12-13 BP 1729 EP 1746 AR PII 905628853 DI 10.1080/10826080802345341 PG 18 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 374CL UT WOS:000261019900004 PM 19016162 ER PT J AU Else, IRN Andrade, NN AF Else, Iwalani R. N. Andrade, Naleen N. BE Leong, FTL Leach, MM TI Suicide Among Indigenous Pacific Islanders in the United States A Historical Perspective SO SUICIDE AMONG RACIAL AND ETHNIC MINORITY GROUPS: THEORY, RESEARCH, AND PRACTICE SE Series in Death Dying and Bereavement LA English DT Article; Book Chapter ID NATIVE HAWAIIAN ADOLESCENTS; PEOPLE; STRESS; HEALTH C1 [Else, Iwalani R. N.; Andrade, Naleen N.] Univ Hawaii Manoa, John A Burns Sch Med, Dept Psychiat, Honolulu, HI 96822 USA. [Andrade, Naleen N.] NIMH, Bethesda, MD 20892 USA. RP Else, IRN (reprint author), Univ Hawaii Manoa, John A Burns Sch Med, Dept Psychiat, Honolulu, HI 96822 USA. NR 53 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-93819-5 J9 SER DEATH DYING PY 2008 BP 143 EP 172 PG 30 WC Psychology, Clinical; Ethnic Studies; Psychiatry SC Psychology; Ethnic Studies; Psychiatry GA BUM41 UT WOS:000289776200008 ER PT J AU Molock, SD Matlin, S Prempeh, H AF Molock, Sherry Davis Matlin, Samantha Prempeh, Henry BE Leong, FTL Leach, MM TI Clinical and Research Training in Suicidality in Ethnic Communities SO SUICIDE AMONG RACIAL AND ETHNIC MINORITY GROUPS: THEORY, RESEARCH, AND PRACTICE SE Series in Death Dying and Bereavement LA English DT Article; Book Chapter ID MENTAL-HEALTH-SERVICES; AMERICAN COMMUNITY; PUBLIC-HEALTH; UNITED-STATES; RISK-FACTORS; INTERVENTION; ADOLESCENTS; COMPETENCE; PREVALENCE; PSYCHOLOGY C1 [Molock, Sherry Davis; Matlin, Samantha] George Washington Univ, Doctoral Program Clin Community Psychol, Washington, DC 20052 USA. [Molock, Sherry Davis] NIMH, Bethesda, MD USA. RP Molock, SD (reprint author), George Washington Univ, Doctoral Program Clin Community Psychol, Washington, DC 20052 USA. NR 77 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-203-93819-5 J9 SER DEATH DYING PY 2008 BP 275 EP 295 PG 21 WC Psychology, Clinical; Ethnic Studies; Psychiatry SC Psychology; Ethnic Studies; Psychiatry GA BUM41 UT WOS:000289776200013 ER PT J AU Martinic, M Measham, F AF Martinic, Marjana Measham, Fiona BE Martinic, M Measham, F TI Extreme Drinking SO SWIMMING WITH CROCODILES: THE CULTURE OF EXTREME DRINKING SE ICAP Series on Alcohol in Society LA English DT Article; Book Chapter ID BINGE-DRINKING; ALCOHOL; COLLEGE; CONSEQUENCES; DRUNKENNESS; CONSUMPTION; STUDENTS; LEVEL; UK C1 [Martinic, Marjana] ICAP, London, England. [Martinic, Marjana] Univ Virginia, Sch Med, Charlottesville, VA 22903 USA. [Martinic, Marjana] Natl Inst Hlth, Bethesda, MD USA. [Measham, Fiona] Univ Lancaster, Dept Appl Social Sci, Lancaster LA1 4YW, England. RP Martinic, M (reprint author), ICAP, London, England. NR 35 TC 17 Z9 18 U1 0 U2 0 PU ROUTLEDGE PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-415-95548-5 J9 ICAP SER ALCOHOL SOC PY 2008 BP 1 EP 12 PG 12 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA BUW13 UT WOS:000290486300001 ER PT J AU Thanos, PK Michaelides, M Piyis, YK Wang, GJ Volkow, ND AF Thanos, Panayotis K. Michaelides, Michael Piyis, Yiannis K. Wang, Gene-Jack Volkow, Nora D. TI Food restriction markedly increases dopamine d2 receptor (D2R) in a rat model of obesity as assessed with in-vivo mu PET Imaging ([C-11] raclopride) and in-vitro ([H-3] spiperone) autoradiography SO SYNAPSE LA English DT Article DE drug abuse; addiction; gene therapy; reward; environment; mu PET; beta-imager ID POSITRON-EMISSION-TOMOGRAPHY; DECREASES EXTRACELLULAR DOPAMINE; ZUCKER RATS; NUCLEUS-ACCUMBENS; AUTOMATED ALGORITHM; GLUCOSE-METABOLISM; HARDERIAN GLANDS; DORSAL STRIATUM; DRUG-ADDICTION; MESSENGER-RNA AB Introduction: Dopamine (DA) regulates food intake by modulating food reward and motivation but its involvement in obesity is much less understood. Recent evidence points to the involvement of leptin in the DA-related modulation of food intake. Here we assess DA D2 receptors (D2R) in a genetic rodent obesity model characterized by leptin-receptor deficiency and assess the influence of food restriction on these receptors. Methods: We compared D2R levels between Zucker Obese (fa/fa) and Lean (Fa/Fa) rats at 1 and 4 months of age and in two different feeding conditions (restricted and unrestricted food access) using in-vivo mu PET imaging ([C-11] raclopride, which is a method sensitive to competition with endogenous DA) and in-vitro ([H-3] spiperone washed to ensure no competition with endogenous DA) autoradiography (ARG). Results: Both ARG and mu PET showed that D2R were higher at 1 month than at 4 months of age and that food restricted animals had higher D2R than unrestricted animals. However there were significant differences in the results obtained at 4 months between ARG and mu PET. ARG showed that at 1 month and at 4 months unrestricted lean rats (Le U) had significantly higher D2R binding than obese unrestricted rats (Ob U) but showed no differences between restricted obese (Ob R) and restricted lean rats (Le R). It also showed that D2R decline between 1 and 4 months of age was significantly attenuated in food restricted rats [both obese and lean]. In contrast, mu PET showed that at 4 months of age, Ob U showed greater D2R availability than Le U rats but like ARG showed no differences between Ob R and Le R rats. Conclusion: The lower D2R binding in Ob U than Le U rats observed with ARG most likely reflects decreases in striatal D2 receptors levels whereas the increased availability observed with mu PET is likely to reflect reduced DA release (resulting in decreased competition with endogenous DA). Lack of a significant difference between Ob R and Le R suggests that the differences in dopamine activity and D2R levels between Ob and Le Zucker rats are modulated by access to food. The ARG finding of an attenuation of the age-related loss of D2R binding corroborates previous studies of the salutary effects of food restriction in the aging process. Because [C-11] raclopride is sensitive to competition with endogenous DA, the higher D2R binding in obese rats with raclopride despite the lower D2R levels shown with spiperone could reflect lower extracellular DA in the Ob rats and merits further investigation. C1 Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol Lab, Upton, NY 11973 USA. NIH, NIAAA, Dept Hlth & Human Serv, Lab Neuroimaging, Bethesda, MD 20892 USA. RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol Lab, Upton, NY 11973 USA. EM thanos@bnl.gov RI Michaelides, Michael/K-4736-2013 OI Michaelides, Michael/0000-0003-0398-4917 FU Intramural NIH HHS; NIAAA NIH HHS [AA07574, AA07611, AA 11034] NR 59 TC 75 Z9 76 U1 0 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JAN PY 2008 VL 62 IS 1 BP 50 EP 61 DI 10.1002/syn.20468 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 233PE UT WOS:000251102000007 PM 17960763 ER PT J AU Kumar, V Tomar, S Patel, R Yousaf, A Parmar, VS Malhotra, SV AF Kumar, Vineet Tomar, Shilpi Patel, Ronak Yousaf, Ahmad Parmar, Virinder S. Malhotra, Sanjay V. TI FeCl(3)-catalyzed Pechmann synthesis of coumarins in ionic liquids SO SYNTHETIC COMMUNICATIONS LA English DT Article DE coumarins; ionic liquids; pachmann condensation; recyclability ID SELECTIVE BENZOYLATION; EFFICIENT; CONDENSATION; NUCLEOSIDES; DERIVATIVES; ALKYLATION; CATALYSIS AB The synthesis of coumarin derivatives via Pechmann reaction using anhydrous FeCl(3) as Lewis acid catalyst in ionic liquid medium has been carried out. The best results were obtained (yields as high as 89%) with ionic liquids having bis(triflic)imide as a counteranion. The ionic liquid could easily be recovered and reused. C1 [Kumar, Vineet; Patel, Ronak; Yousaf, Ahmad; Malhotra, Sanjay V.] New Jersey Inst Technol, Dept Chem & Environm Sci, Newark, NJ 07102 USA. [Tomar, Shilpi; Parmar, Virinder S.] Univ Delhi, Dept Chem, Delhi 110007, India. RP Malhotra, SV (reprint author), NCI, Lab Synthet Chem, SAIC Frederick Inc, 1050 Boyles St, Frederick, MD 21702 USA. EM malhotrasa@mail.nih.gov FU Bristol Myers Squibb; American Chemical Society SEED FX A. Y. acknowledges Bristol Myers Squibb for partial support through an undergraduate research grant. R. P. thanks the American Chemical Society SEED program for summer support. NR 35 TC 25 Z9 25 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0039-7911 J9 SYNTHETIC COMMUN JI Synth. Commun. PY 2008 VL 38 IS 15 BP 2646 EP 2654 DI 10.1080/00397910802219569 PG 9 WC Chemistry, Organic SC Chemistry GA 345ES UT WOS:000258979500016 ER PT J AU Malhotra, S Andal, R Kumar, V AF Malhotra, Sanjay V. Andal, Richard P. Kumar, Vineet TI Aminolysis of Epoxides in Ionic Liquid 1-Ethylpyridinium Trifluoroacetate as Green and Efficient Reaction Medium SO SYNTHETIC COMMUNICATIONS LA English DT Article DE -Amino alcohols; aminolysis; epoxides; ionic liquids ID PRESSURE ORGANIC-CHEMISTRY; AROMATIC-AMINES; MESO-EPOXIDES; ASYMMETRIC AMINOHYDROXYLATION; STEREOSELECTIVE-SYNTHESIS; CATALYZED AMINOLYSIS; ALCOHOLS; OXIRANES; CLEAVAGE; ALKYLAMIDES AB Aminolysis of epoxides has been carried out using the ionic liquid 1-ethylpyridinium trifluoroacetate ([EtPy][TFA]) as reaction medium. The reactions went smoothly under mild conditions without any catalyst to afford corresponding -aminoalcohols in high conversions. Moreover, further enhancement in the conversions was observed when AlCl3 was used as Lewis acid catalyst. C1 [Malhotra, Sanjay V.; Andal, Richard P.; Kumar, Vineet] New Jersey Inst Technol, Dept Chem & Environm Sci, Newark, NJ 07102 USA. RP Malhotra, SV (reprint author), NCI, Lab Synthet Chem, SAIC Frederick Inc, 1050 Boyles St, Frederick, MD 21702 USA. EM malhotrasa@mail.nih.gov FU ristol-Myers Squibb, Lawrenceville FX R. P.A. acknowledge Bristol-Myers Squibb, Lawrenceville, N. J. USA, for summer undergraduate research support. NR 48 TC 5 Z9 5 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0039-7911 J9 SYNTHETIC COMMUN JI Synth. Commun. PY 2008 VL 38 IS 23 BP 4160 EP 4169 AR PII 905011607 DI 10.1080/00397910802323056 PG 10 WC Chemistry, Organic SC Chemistry GA 368GD UT WOS:000260608700010 ER PT S AU Reid, E Chen, HC AF Reid, Edna Chen, Hsinchun BE Chen, H Reid, E Sinai, J Silke, A Ganor, B TI DOMAIN MAPPING OF CONTEMPORARY TERRORISM RESEARCH SO TERRORISM INFORMATICS: KNOWLEDGE MANAGEMENT AND DATA MINING FOR HOMELAND SECURITY SE Integrated Series in Information Systems LA English DT Article; Book Chapter ID AUTHOR COCITATION ANALYSIS AB Mapping a domain involves mining, analyzing, charting, and visualizing a research area according to experts, institutions, topics, publications, and social networks. This chapter presents an overview of contemporary terrorism research by applying domain visualization techniques to the literature and author citation data from the years 1965 to 2003. The data were gathered from ten databases such as the ISI Web of Science then analyzed using an integrated knowledge mapping framework that includes selected techniques such as self-organizing map (SOM), content map analysis, and co-citation analysis. The analysis revealed (1) 42 key terrorism researchers and their institutional affiliations; (2) their influential publications; (3) a shift from focusing on terrorism as a low-intensity conflict to an emphasis on it as a strategic threat to world powers with increased focus on Osama Bin Laden; and (4) clusters of terrorism researchers who work in similar research areas as identified by co-citation and block-modeling maps. C1 [Reid, Edna] Clarion Univ Pennsylvania, Dept Lib Sci, Clarion, PA USA. [Chen, Hsinchun] Univ Arizona, MIS Dept, Tucson, AZ USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. [Chen, Hsinchun] Natl Lib China, Beijing, Peoples R China. [Reid, Edna] Univ Arizona, Artificial Intelligence Lab, Tucson, AZ USA. [Reid, Edna] Nanyang Technol Univ, Nanyang Business Sch, Div Informat Studies, Singapore, Singapore. [Reid, Edna] Soc Competit Intelligence Profess Singapore SCIPS, Singapore, Singapore. [Reid, Edna] Rutgers State Univ, Sch Commun Informat & Lib Studies, Piscataway, NJ 08855 USA. [Reid, Edna] Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Reid, E (reprint author), Clarion Univ Pennsylvania, Dept Lib Sci, Clarion, PA USA. EM ereid@clarion.edu; hchen@eller.arizona.edu NR 36 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-71613-8 J9 INTEGR SER INFORM SY PY 2008 VL 18 BP 3 EP 26 D2 10.1007/978-0-387-71613-8 PG 24 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Political Science SC Computer Science; Information Science & Library Science; Government & Law GA BLM35 UT WOS:000270526000002 ER PT S AU Chen, HC Qin, JL Reid, E Zhou, YL Sageman, M AF Chen, Hsinchun Qin, Jialun Reid, Edna Zhou, Yilu Sageman, Marc BE Chen, H Reid, E Sinai, J Silke, A Ganor, B TI CASE STUDY OF JIHAD ON THE WEB A Web Mining Approach SO TERRORISM INFORMATICS: KNOWLEDGE MANAGEMENT AND DATA MINING FOR HOMELAND SECURITY SE Integrated Series in Information Systems LA English DT Article; Book Chapter AB Terrorist and extremist groups and their sympathizers have found a cost-effective resource to advance their courses by posting high-impact Websites with short shelf-lives. Because of their evanescent nature, terrorism research communities require unrestrained access to digitally archived Websites to mine their contents and pursue various types of analyses. Organizations that specialize in capturing, archiving, and analyzing Jihad terrorist Websites employ different, manual-based analysis techniques that are 'hidden' from the research communities. This chapter proposes the development of automated or semi-automated procedures and systematic methodologies for capturing Jihad terrorist Website data and its subsequent analyses. By analyzing the content of hyperlinked terrorist Websites and constructing visual social network maps, our study is able to generate an integrated approach to the study of Jihad terrorism, their network structure, component clusters, and cluster affinity. C1 [Chen, Hsinchun; Reid, Edna; Zhou, Yilu] Univ Arizona, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Qin, Jialun] Univ Massachusetts Lowell, Dept Management, Lowell, MA USA. [Reid, Edna] Clarion Univ Pennsylvania, Dept Lib Sci, Clarion, PA USA. [Zhou, Yilu] George Washington Univ, Informat Syst & Technol Management Dept, Washington, DC USA. [Sageman, Marc] Sageman Consulting LLC, Rockville, MD USA. [Sageman, Marc] Ctr Strateg & Int Studies, Washington, DC 20006 USA. [Reid, Edna] Nanyang Technol Univ, Nanyang Business Sch, Div Informat Studies, Singapore, Singapore. [Reid, Edna] Rutgers State Univ, Sch Commun Informat & Lib Studies, Piscataway, NJ 08855 USA. [Reid, Edna] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Chen, HC (reprint author), Univ Arizona, Artificial Intelligence Lab, Tucson, AZ 85721 USA. EM hchen@eller.arizona.edu; jialun_qin@uml.edu; ereid@clarion.edu; yzhou@gwu.edu; sageman@post.harvard.edu; ereid@clarion.edu NR 20 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-71613-8 J9 INTEGR SER INFORM SY PY 2008 VL 18 BP 221 EP 235 D2 10.1007/978-0-387-71613-8 PG 15 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Political Science SC Computer Science; Information Science & Library Science; Government & Law GA BLM35 UT WOS:000270526000012 ER PT S AU Qin, JL Zhou, YL Reid, E Chen, HC AF Qin, Jialun Zhou, Yilu Reid, Edna Chen, Hsinchun BE Chen, H Reid, E Sinai, J Silke, A Ganor, B TI STUDYING GLOBAL EXTREMIST ORGANIZATIONS' INTERNET PRESENCE USING THE DARK WEB ATTRIBUTE SYSTEM A Three Region Comparison Study SO TERRORISM INFORMATICS: KNOWLEDGE MANAGEMENT AND DATA MINING FOR HOMELAND SECURITY SE Integrated Series in Information Systems LA English DT Article; Book Chapter AB Nowadays, global extremist organizations are heavily utilizing Internet technologies to increase their abilities to influence the world. Studying those global extremist organizations' Internet presence would allow us to better understand extremist organizations' technical sophistication and their propaganda plans. However, due to the lack of efficient automatic methodologies, few previous researches have attempted to study the extremist organizations' online presence on a global scale. In this work, we explore an integrated approach for collecting and analyzing extremist online presence. We employed automatic Web crawling techniques to build a comprehensive extremist Web collection which contains around 1.7 million multimedia Web documents. We then used a systematic content analysis tool called the Dark Web Attribute System to study these extremist organizations' Internet usage from three perspectives: technical sophistication, content richness, and Web interactivity. We also conducted statistical analysis to cross-compare the technical sophistication and effectiveness of Web sites created by extremist groups from different regions. Our analysis results showed that all extremist organizations covered in this study demonstrated high level of technical sophistication in their Web presence but extremist organizations from different regions have different patterns in their Internet technology deployment and online content delivery. Our analysis results would help domain experts deepen their understanding on the global extremism movements and make better counter-extremism measures on the Internet. C1 [Qin, Jialun] Univ Massachusetts Lowell, Dept Management, Lowell, MA USA. [Zhou, Yilu] George Washington Univ, Dept Informat Syst & Technol Management, Washington, DC USA. [Reid, Edna] Clarion Univ Pennsylvania, Dept Lib Sci, Clarion, PA USA. [Chen, Hsinchun] Univ Arizona, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Reid, Edna] Univ Arizona, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Reid, Edna] Nanyang Technol Univ, Nanyang Business Sch, Div Informat Studies, Singapore, Singapore. [Reid, Edna] Soc Competit Intelligence Profess Singapore SCIPS, Singapore, Singapore. [Reid, Edna] Rutgers State Univ, Sch Commun Informat & Lib Studies, Piscataway, NJ 08855 USA. [Reid, Edna] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Qin, JL (reprint author), Univ Massachusetts Lowell, Dept Management, Lowell, MA USA. EM jialun_qin@uml.edu; yzhou@gwu.edu; ereid@clarion.edu; hchen@eller.arizona.edu NR 43 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-71613-8 J9 INTEGR SER INFORM SY PY 2008 VL 18 BP 237 EP 266 D2 10.1007/978-0-387-71613-8 PG 30 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Political Science SC Computer Science; Information Science & Library Science; Government & Law GA BLM35 UT WOS:000270526000013 ER PT S AU Salem, A Reid, E Chen, HC AF Salem, Arab Reid, Edna Chen, Hsinchun BE Chen, H Reid, E Sinai, J Silke, A Ganor, B TI CONTENT ANALYSIS OF JIHADI EXTREMIST GROUPS' VIDEOS SO TERRORISM INFORMATICS: KNOWLEDGE MANAGEMENT AND DATA MINING FOR HOMELAND SECURITY SE Integrated Series in Information Systems LA English DT Article; Book Chapter ID VIOLENCE AB This paper presents an exploratory study of jihadi extremist groups' videos using content analysis and a multimedia coding tool to explore the types of video, groups' modus operandi, and production features that lend support to extremist groups. The videos convey messages powerful enough to mobilize members, sympathizers, and even new recruits to launch attacks that are once again captured (on video) and disseminated globally via the Internet. They communicate the effectiveness of the campaigns and have a much wider impact because they are media rich with nonverbal cues and vivid images of events that can evoke not only a multitude of psychological and emotional responses but also violent reactions. The videos are important for jihadi extremist groups' learning, training, and recruitment. In addition, the content collection and analysis of extremist groups' videos can help policy makers, intelligence analysts, and researchers better understand the extremist groups' terror campaigns and modus operandi, and help suggest counter-intelligence strategies and tactics for troop training. C1 [Chen, Hsinchun] Univ Arizona, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Reid, Edna] Clarion Univ Pennsylvania, Dept Lib Sci, Clarion, PA USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. [Chen, Hsinchun] Natl Lib China, Beijing, Peoples R China. [Reid, Edna] Univ Arizona, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Reid, Edna] Nanyang Technol Univ, Nanyang Business Sch, Div Informat Studies, Singapore, Singapore. [Reid, Edna] Rutgers State Univ, Sch Commun Informat & Lib Studies, Piscataway, NJ 08855 USA. [Reid, Edna] Univ Calif Berkeley, Berkeley, CA 94720 USA. EM arabsalem@gmail.com; reid@clarion.edu; hchen@eller.arizona.edu NR 44 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-71613-8 J9 INTEGR SER INFORM SY PY 2008 VL 18 BP 267 EP 284 D2 10.1007/978-0-387-71613-8 PG 18 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Political Science SC Computer Science; Information Science & Library Science; Government & Law GA BLM35 UT WOS:000270526000014 ER PT S AU Abbasi, A Chen, HC AF Abbasi, Ahmed Chen, Hsinchun BE Chen, H Reid, E Sinai, J Silke, A Ganor, B TI ANALYSIS OF AFFECT INTENSITIES IN EXTREMIST GROUP FORUMS SO TERRORISM INFORMATICS: KNOWLEDGE MANAGEMENT AND DATA MINING FOR HOMELAND SECURITY SE Integrated Series in Information Systems LA English DT Article; Book Chapter ID VIOLENCE; WEB AB Affects play an important role in influencing people's perceptions and decision making. Affect analysis is useful for measuring the presence of hate, violence, and the resulting propaganda dissemination across extremist groups. In this study we performed affect analysis of U. S. and Middle Eastern extremist group forum postings. We constructed an affect lexicon using a probabilistic disambiguation technique to measure and visualize usage of violence and hate affects. These techniques facilitate in depth analysis of multilingual content. The proposed approach was evaluated by applying it across 16 U.S. supremacist and Middle Eastern extremist group forums. Analysis across regions reveals that the Middle Eastern test bed forums have considerably greater violence intensity than the U. S. groups. There is also a strong linear relationship between the usage of hate and violence across the Middle Eastern messages. C1 [Abbasi, Ahmed; Chen, Hsinchun] Univ Arizona, Dept Management Informat Syst, Tucson, AZ 85721 USA. [Chen, Hsinchun] Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Hsinchun] Natl Lib China, Beijing, Peoples R China. [Abbasi, Ahmed] Univ Arizona, Artificial Intelligence Lab, Tucson, AZ 85721 USA. [Chen, Hsinchun] Acad Sinica, Taipei, Taiwan. RP Abbasi, A (reprint author), Univ Arizona, Dept Management Informat Syst, Tucson, AZ 85721 USA. EM aabbasi@email.arizona.edu; hchen@eller.arizona.edu NR 43 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1571-0270 BN 978-0-387-71613-8 J9 INTEGR SER INFORM SY PY 2008 VL 18 BP 285 EP 307 D2 10.1007/978-0-387-71613-8 PG 23 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Political Science SC Computer Science; Information Science & Library Science; Government & Law GA BLM35 UT WOS:000270526000015 ER PT J AU Ventegodt, S Kandel, I Merrick, J AF Ventegodt, Soren Kandel, Isack Merrick, Joav TI Clinical holistic medicine: Avoiding the freudian trap of sexual transference and countertransference in psychodynamic therapy SO THESCIENTIFICWORLDJOURNAL LA English DT Article DE sexuality; sexual healing; infantile autoerotism; schizophrenia; spontaneous regression; physical holding; therapeutic touch; clinical holistic medicine; psychodynamic psychotherapy; STPP; CAM; psychoanalysis; sexual transference and countertransference; vaginal acupressure; Freud's trap; Denmark ID HIPPOCRATIC PELVIC MASSAGE; SCALE SOC-II; PHYSICAL HEALTH; BIOLOGICAL INFORMATION; CASE STORY; ANTONOVSKYS SENSE; COHERENCE; PSYCHOTHERAPY; CONSCIOUSNESS; BODYWORK AB Sexual transference and countertransference can make therapy slow and inefficient when libidinous gratification becomes more important for both the patient and the therapist than real therapeutic progress. Sexual transference is normal when working with a patient's repressed sexuality, but the therapeutic rule of not touching often hinders the integration of sexual traumas, as this needs physical holding. So the patient is often left with sexual, Oedipal energies projected onto the therapist as an "idealized father" figure. The strong and lasting sexual desire for the therapist without any healing taking place can prolong therapy for many years, as it often does in psychodynamic psychotherapy and psychoanalysis. We call this problem "Freud's Trap". Freud used intimate bodywork, such as massage, in the beginning of his career, but stopped, presumably for moral and political reasons. In the tradition of psychoanalysis, touch is therefore not allowed. Recent research in clinical holistic medicine (CHM), salutogenesis, and sexual healing has shown that touch and bodywork (an integral part of medicine since Hippocrates) are as important for healing as conversational therapy. CHM allows the patient to regress spontaneously to early sexual and emotional traumas, and to heal the deep wounds on body, soul, and sexual character from arrested psychosexual development. CHM treats sexuality in therapy more as the patient's internal affair (i.e., energy work) and less as a thing going on between the patient and the therapist (i.e., transference). This accelerates healing, and reduces sexual transference and the need for mourning at the end of therapy. C1 [Ventegodt, Soren] Qual Life Res Ctr, DK-2100 Copenhagen, Denmark. [Ventegodt, Soren] Res Clin Hoilist Med, Copenhagen, Denmark. [Ventegodt, Soren] Nord Sch Holist Med, Copenhagen, Denmark. [Ventegodt, Soren] Scandavian Fdn Holist Med, Sandviken, Sweden. [Ventegodt, Soren] Interuniv Coll, Graz, Austria. [Kandel, Isack] Ariel Univ, Ctr Samaria, Ariel, Israel. [Kandel, Isack; Merrick, Joav] NICHHD, Bethesda, MD USA. [Merrick, Joav] Off Med Director, Div Mental Retardat, Minist Social Affairs, Jerusalem, Israel. [Merrick, Joav] Univ Kentucky, Kentucky Childrens Hosp, Lexington, KY USA. RP Ventegodt, S (reprint author), Qual Life Res Ctr, Classensgade 11C,1 Sal, DK-2100 Copenhagen, Denmark. EM ventegodt@livskvalitet.org NR 63 TC 0 Z9 0 U1 0 U2 5 PU THESCIENTIFICWORLD LTD PI NEWBURY PA 29-34, VENTURE WEST, NEW GREENHAM PARK, NEWBURY, BERKSHIRE RG19 6HX, ENGLAND SN 1537-744X J9 THESCIENTIFICWORLDJO JI TheScientificWorldJOURNAL PY 2008 VL 8 BP 371 EP 383 DI 10.1100/tsw.2008.27 PG 13 WC Environmental Sciences; Multidisciplinary Sciences SC Environmental Sciences & Ecology; Science & Technology - Other Topics GA 288KJ UT WOS:000254985000040 PM 18454245 ER PT J AU Anderson, JM Valenzuela, JG AF Anderson, J. M. Valenzuela, J. G. BE Bowman, AS Nuttall, PA TI Tick saliva: from pharmacology and biochemistry to transcriptome analysis and functional genomics SO TICKS: BIOLOGY, DISEASE AND CONTROL LA English DT Article; Book Chapter ID LONE STAR TICK; ORNITHODOROS-SAVIGNYI ACARI; AMBLYOMMA-AMERICANUM L.; PLATELET-AGGREGATION INHIBITOR; ANTI-COMPLEMENT ACTIVITY; IXODES-SCAPULARIS TICKS; FACTOR XA INHIBITOR; BOOPHILUS-MICROPLUS; DERMACENTOR-ANDERSONI; SOFT TICK C1 [Anderson, J. M.; Valenzuela, J. G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Anderson, JM (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Room 2E-22, Rockville, MD 20852 USA. NR 107 TC 10 Z9 10 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-86761-0 PY 2008 BP 92 EP 107 DI 10.1017/CBO9780511551802.005 D2 10.1017/CBO9780511551802 PG 16 WC Entomology; Parasitology SC Entomology; Parasitology GA BDX36 UT WOS:000315527800005 ER PT J AU Grubhoffer, L Rego, ROM Hajdusek, O Hypsa, V Kovar, V Rudenko, N Oliver, JH AF Grubhoffer, L. Rego, R. O. M. Hajdusek, O. Hypsa, V. Kovar, V. Rudenko, N. Oliver, J. H., Jr. BE Bowman, AS Nuttall, PA TI Tick lectins and fibrinogen-related proteins SO TICKS: BIOLOGY, DISEASE AND CONTROL LA English DT Article; Book Chapter ID CARBOHYDRATE-RECOGNITION DOMAINS; LYME-DISEASE SPIROCHETE; ORNITHODOROS-MOUBATA ACARI; INNATE IMMUNE-RESPONSE; MANNAN-BINDING-LECTIN; BORRELIA-BURGDORFERI; IXODES-RICINUS; ANIMAL LECTINS; SOFT TICK; HEMOLYMPH LECTIN C1 [Grubhoffer, L.; Kovar, V.; Rudenko, N.] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic. [Rego, R. O. M.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Hajdusek, O.; Hypsa, V.] Univ South Bohemia, Fac Biol Sci, Ceske Budejovice 37005, Czech Republic. [Oliver, J. H., Jr.] Georgia So Univ, Inst Arthropodol & Parasitol, Statesboro, GA 30460 USA. RP Grubhoffer, L (reprint author), Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, Branisovska 31, CR-37005 Ceske Budejovice, Czech Republic. RI Rego, Ryan/G-9773-2014; Rudenko, Nataliia (Natasha)/J-8571-2012; Grubhoffer, Libor/G-9762-2014; Hajdusek, Ondrej/G-7911-2014; Hypsa, Vaclav/G-9847-2014 OI Rego, Ryan/0000-0001-6932-0940; NR 124 TC 4 Z9 4 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-86761-0 PY 2008 BP 127 EP 142 DI 10.1017/CBO9780511551802.007 D2 10.1017/CBO9780511551802 PG 16 WC Entomology; Parasitology SC Entomology; Parasitology GA BDX36 UT WOS:000315527800007 ER PT J AU Bianco, P Robey, PG Pennesi, G Cancedda, R AF Bianco, Paolo Robey, Pamela Gehron Pennesi, Giuseppina Cancedda, Ranieri BE Thomsen, P Lindahl, A Hubbell, J Williams, D Cancedda, R DeBruijn, J Sohier, J TI Cell source SO TISSUE ENGINEERING SE Academic Press Series in Biomedical Engineering LA English DT Article; Book Chapter ID MESENCHYMAL STEM-CELLS; BONE MARROW CELLS; CORD-BLOOD; LYMPHOCYTE-PROLIFERATION; MUSCLE REGENERATION; UNRELATED DONORS; CLONAL ANALYSIS; VASCULAR NICHE; HAIR-FOLLICLES; T-CELLS C1 [Bianco, Paolo] Univ Roma La Sapienza, Rome, Italy. [Robey, Pamela Gehron] NIH, Bethesda, MD 20892 USA. [Pennesi, Giuseppina; Cancedda, Ranieri] Univ Genoa, Genoa, Italy. [Cancedda, Ranieri] Ist Nazl Ric Canc, I-16132 Genoa, Italy. RP Bianco, P (reprint author), Univ Roma La Sapienza, Rome, Italy. NR 80 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-055919-3 J9 ACAD PR SER BIOM ENG PY 2008 BP 279 EP 306 DI 10.1016/B978-0-12-370869-4.00010-0 PG 28 WC Cell & Tissue Engineering; Engineering, Biomedical; Materials Science, Biomaterials SC Cell Biology; Engineering; Materials Science GA BCW80 UT WOS:000311795600012 ER PT J AU Cotrim, AP Baum, BJ AF Cotrim, Ana P. Baum, Bruce J. TI Gene Therapy: Some History, Applications, Problems, and Prospects SO TOXICOLOGIC PATHOLOGY LA English DT Article DE Salivary gland; animal models; cell(ular) pathology ID SEVERE COMBINED IMMUNODEFICIENCY; RAT SALIVARY-GLANDS; SJOGRENS-SYNDROME; SUPEROXIDE-DISMUTASE; MEDIATED TRANSFER; MURINE MODEL; THERAPEUTICS; DISEASE; CDNA; TRANSDUCTION AB The concept of transferring genes to tissues for clinical applications has been discussed for nearly half a century, but our ability to manipulate genetic material via recombinant DNA technology has brought this goal to reality. While originally conceived as a way to treat life-threatening disorders (inborn errors, cancers) refractory to conventional treatment, gene therapy now is considered for many non-life-threatening conditions, including those adversely affecting a patient's quality of life. The lack of suitable treatment has become a rational basis for extending the scope of gene therapy. This manuscript reviews the general methods by which genes are transferred as well as diverse examples of clinical applications (acquired tissue damage, upper gastrointestinal tract infection, autoimmune disease, systemic protein deficiency). Despite some well-publicized problems, gene therapy has made substantive progress, including tangible success, albeit much slower than was initially predicted. Although gene therapy is still at a fairly primitive stage, it is firmly science based. There is justifiable optimism that with increased pathobiological understanding and biotechnological improvements, gene therapy will become a standard part of clinical practice within 20 years. C1 [Cotrim, Ana P.; Baum, Bruce J.] NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. RP Cotrim, AP (reprint author), NIDCR, GTTB, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM acotrim@nidcr.nih.gov FU National Institute of Dental and Craniofacial Research FX The authors' research is supported by the intramural research program of the National Institute of Dental and Craniofacial Research. NR 41 TC 47 Z9 52 U1 4 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 BP 97 EP 103 DI 10.1177/0192623307309925 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900012 PM 18337227 ER PT J AU Therrien, JP Pfutzner, W Vogel, JC AF Therrien, Jean-Philippe Pfuetzner, Wolfgang Vogel, Jonathan C. TI An Approach to Achieve Long-Term Expression in Skin Gene Therapy SO TOXICOLOGIC PATHOLOGY LA English DT Article DE Human skin; gene therapy; multidrug resistance gene; bicistronic retroviral vectors; systemic delivery; topical selection ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; MULTIDRUG-RESISTANCE GENE; EPIDERMAL STEM-CELLS; BICISTRONIC RETROVIRAL VECTOR; ATRIAL-NATRIURETIC-PEPTIDE; GENETICALLY-MODIFIED SKIN; X-LINKED ICHTHYOSIS; HEMATOPOIETIC-CELLS; VII COLLAGEN; IN-VIVO AB For gene therapy purposes, the skin is an attractive organ to target for systemic delivery of therapeutic proteins to treat systemic diseases, skin diseases, or skin cancer. To achieve long-term stable expression of a therapeutic gene in keratinocytes (KC), we have developed an approach using a bicistronic retroviral vector expressing the desired therapeutic gene linked to a selectable marker (multidrug resistant gene, MDR) that is then introduced into KC and fibroblasts (FB) to create genetically modified human skin equivalent (HSE). After grafting the HSE onto immunocompromised mice, topical colchicine treatment is used to select and enrich for genetically modified keratinocyte stem cells (KSC) that express MDR and are resistant to colchicine's antimitotic effects. Both the apparatus for topical colchicine delivery and the colchicine doses have been optimized for application to human skin. This approach can be validated by systemic delivery of therapeutic factors such as erythropoietin and the antihypertensive atrial natriuretic peptide. C1 [Therrien, Jean-Philippe; Vogel, Jonathan C.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Pfuetzner, Wolfgang] Univ Marburg, Dept Dermatol & Allergol, Marburg, Germany. RP Therrien, JP (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N254,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. EM therriej@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; Canadian Institutes of Health Research (CIHR) FX We thank Carole Yee and Girish Patel for their advice and suggestions to improve this manuscript. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. JPT was a recipient of a postdoctoral fellowship from the Canadian Institutes of Health Research (CIHR). NR 60 TC 6 Z9 6 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 BP 104 EP 111 DI 10.1177/0192623307312705 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900013 PM 18337228 ER PT J AU Heatherly, A Yoshizawa, K Malarkey, DE Walker, NJ Nyska, A AF Heatherly, Allison Yoshizawa, Katsuhiko Malarkey, David E. Walker, Nigel J. Nyska, Abraham TI A Critical Comparison of Murine Pathology and Epidemiological Data of Dioxins and PCBs SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Heatherly, Allison; Malarkey, David E.] NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. [Yoshizawa, Katsuhiko] Astellas Pharma Inc, Drug Safety Res Labs, Osaka, Japan. [Walker, Nigel J.] NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P1 BP 149 EP 149 DI 10.1177/0192623307312230 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900020 ER PT J AU Kolenda-Roberts, H Elwell, M Ernst, H Greaves, P Hardisty, J Malarkey, D Mann, P Tellier, P AF Kolenda-Roberts, Holly Elwell, Michael Ernst, Heinrich Greaves, Peter Hardisty, Jerry Malarkey, David Mann, Peter Tellier, Pierre TI Diagnostic Criteria for Selected Peroxisome Proliferator-Activated Receptor (PPAR) Agonist-Induced Mesenchymal Lesions in the Rat SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Kolenda-Roberts, Holly; Hardisty, Jerry] Expt Pathol Labs Inc, Res Triangle Pk, NC USA. [Mann, Peter] Expt Pathol Labs Inc, NW, Seattle, WA USA. [Elwell, Michael] Covance Labs, Vienna, VA USA. [Ernst, Heinrich] Fraunhofer Inst Toxicol & Expt Med, Hannover, Germany. [Greaves, Peter] Univ Leicester, Leicester, Leics, England. [Malarkey, David] NIEHS, Res Triangle Pk, NC 27709 USA. [Tellier, Pierre] Charles River Labs, Senneville, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P7 BP 151 EP 151 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900026 ER PT J AU Kolenda-Roberts, H Elwell, M Ernst, H Greaves, P Hardisty, J Malarkey, D Mann, P Tellier, P AF Kolenda-Roberts, Holly Elwell, Michael Ernst, Heinrich Greaves, Peter Hardisty, Jerry Malarkey, David Mann, Peter Tellier, Pierre TI Diagnostic Criteria for Selected Peroxisome Proliferator-Activated Receptor (PPAR) Agonist-Induced Vascular Lesions in the Mouse SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Kolenda-Roberts, Holly; Hardisty, Jerry] Expt Pathol Labs Inc, Res Triangle Pk, NC USA. [Mann, Peter] Expt Pathol Labs Inc, NW, Seattle, WA USA. [Elwell, Michael] Covance Labs, Vienna, VA USA. [Ernst, Heinrich] Fraunhofer Inst Toxicol & Expt Med, Hannover, Germany. [Greaves, Peter] Univ Leicester, Leicester, Leics, England. [Malarkey, David] NIEHS, Res Triangle Pk, NC 27709 USA. [Tellier, Pierre] Charles River Labs, Senneville, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P8 BP 151 EP 152 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900027 ER PT J AU Dixon, D Castro, L Moore, A Kissling, G AF Dixon, Darlene Castro, Lysandra Moore, Alicia Kissling, Grace TI Genistein-Induced Cell Death in Uterine Leiomyoma (UtLM) Cells Is Not by Apoptosis SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Dixon, Darlene; Castro, Lysandra; Moore, Alicia; Kissling, Grace] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P15 BP 154 EP 154 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900034 ER PT J AU Painter, JT Veit, A Flagler, N Miller, R Hardisty, J Dixon, D AF Painter, J. Todd Veit, Allison Flagler, Norris Miller, Rodney Hardisty, Jerry Dixon, Darlene TI Histomorphologic and Immunohistochemical Evaluation of Granular Cell Tumors in B6C3F1 Mice SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Painter, J. Todd; Veit, Allison; Miller, Rodney; Hardisty, Jerry] Expt Pathol Labs Inc, Res Triangle Pk, NC USA. [Veit, Allison; Flagler, Norris; Dixon, Darlene] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P16 BP 154 EP 154 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900035 ER PT J AU Surin, K Williams, K Woody, S Latorre, J Marsh, T Flagler, N Sills, R Ton, T AF Surin, Kezia Williams, Kathryn Woody, Shelly Latorre, John Marsh, Tiwanda Flagler, Norris Sills, Robert Ton, Thai TI Immunohistochemical Analysis of beta-Catenin, Cyclin D1, PCNA, and Cox-2 in Large Intestinal Proliferative Lesions of the F344 Rat Demonstrate that Nuclear beta-Catenin May Represent a Marker for Differentiating Complex Hyperplastic Lesions from Neoplastic Lesions SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Surin, Kezia; Williams, Kathryn; Woody, Shelly; Latorre, John; Marsh, Tiwanda; Flagler, Norris; Sills, Robert; Ton, Thai] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P17 BP 154 EP 155 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900036 ER PT J AU Hoenerhoff, M Datta, S Dimri, G Simpson, M Green, J AF Hoenerhoff, Mark Datta, Sonal Dimri, Goberdhan Simpson, Mark Green, Jeff TI The Polycomb Group Protein Bmi-1 Collaborates with H-Ras to Promote Transformation of Mammary Epithelial Cells and Development of Poorly Differentiated Metastatic Mammary Tumors In Vivo SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Hoenerhoff, Mark; Simpson, Mark; Green, Jeff] NCI, Bethesda, MD 20892 USA. [Datta, Sonal; Dimri, Goberdhan] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Evanston, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P25 BP 157 EP 158 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900044 ER PT J AU Keenan, C Elmore, S Franckecarroll, S Kemp, R Kerlin, R Pletcher, J Rinke, M Schmidt, P Taylor, I Wolf, D AF Keenan, Charlotte Elmore, Susan Franckecarroll, Sabine Kemp, Ramon Kerlin, Roy Pletcher, John Rinke, Matthias Schmidt, Peter Taylor, Ian Wolf, Douglas TI STP Working Group for Historical Control Data of Proliferative Rodent Lesions SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Keenan, Charlotte] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Elmore, Susan] NIEHS, Res Triangle Pk, NC 27709 USA. [Franckecarroll, Sabine] US FDA, Silver Spring, MD USA. [Kemp, Ramon] Merck Res Labs, West Point, PA USA. [Kerlin, Roy] Pfizer Global Res & Dev, Groton, CT USA. [Pletcher, John] Charles River Labs, Frederick, MD USA. [Rinke, Matthias] BayerHealthCare AG, Wuppertal, Germany. [Schmidt, Peter] Pfizer Inc, Kalamazoo, MI USA. [Wolf, Douglas] US EPA, Res Triangle Pk, NC 27711 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P24 BP 157 EP 157 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900043 ER PT J AU Yoshizawa, K Walker, NJ Miller, RA Brix, AE Sells, DM Jokinen, MP Wyde, ME Nyska, A AF Yoshizawa, Katsuhiko Walker, Nigel J. Miller, Rodney A. Brix, Amy E. Sells, Donald M. Jokinen, Michael P. Wyde, Michael E. Nyska, Abraham TI Pulmonary Lesions in Female Harlan SD Rats Following Two-Year Oral Treatment with Dioxins SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Yoshizawa, Katsuhiko] Astellas Pharma Inc, Osaka, Japan. [Yoshizawa, Katsuhiko] Kansai Med Univ, Moriguchi, Osaka 570, Japan. [Walker, Nigel J.; Wyde, Michael E.] NIEHS, Res Triangle Pk, NC 27709 USA. [Miller, Rodney A.; Brix, Amy E.] Expt Pathol Labs Inc, Durham, NC USA. [Sells, Donald M.] Battelle Columbus Labs, Columbus, OH USA. [Jokinen, Michael P.] Pathol Associates Inc, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P52 BP 166 EP 167 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900071 ER PT J AU Yoshizawa, K Brix, AE Sells, DM Jokinen, MP Wyde, ME Walker, NJ Nyska, A AF Yoshizawa, Katsuhiko Brix, Amy E. Sells, Donald M. Jokinen, Michael P. Wyde, Michael E. Walker, Nigel J. Nyska, Abraham TI Reproductive Lesions in Female Harlan Sprague-Dawley Rats Following Two-Year Oral Treatment with Dioxin and Dioxin-Like Compounds SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Yoshizawa, Katsuhiko] Astellas Pharma Inc, Osaka, Japan. [Yoshizawa, Katsuhiko] Kansai Med Univ, Moriguchi, Osaka 570, Japan. [Brix, Amy E.] Expt Pathol Labs Inc, Durham, NC USA. [Sells, Donald M.] Battelle Columbus Labs, Columbus, OH USA. [Jokinen, Michael P.] Pathol Associates Inc, Durham, NC USA. [Wyde, Michael E.; Walker, Nigel J.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P53 BP 167 EP 167 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900072 ER PT J AU Wyde, ME Bordelon, NR Mann, J Hill, G Painter, JT Yoshizawa, K Hebert, CD Bucher, JR Nyska, A AF Wyde, Michael E. Bordelon, Nancy R. Mann, Jill Hill, Georgette Painter, J. Todd Yoshizawa, Katsuhiko Hebert, Charles D. Bucher, John R. Nyska, Abraham TI Subchronic Administration of Indole-3-Carbinol in B6C3F1 Mice and Fischer 344 Rats Is Associated with Increased Hepatic CYP 1A1 and 1A2 Activities, but without Liver Toxicity SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Wyde, Michael E.; Bucher, John R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Hill, Georgette] ILS, Res Triangle Pk, NC USA. [Painter, J. Todd] EPL, Res Triangle Pk, NC USA. [Yoshizawa, Katsuhiko] Astellas Pharma Inc, Osaka, Japan. [Nyska, Abraham] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P57 BP 168 EP 168 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900076 ER PT J AU Flagler, N Ney, E Johnson, K Malarkey, D AF Flagler, Norris Ney, Eli Johnson, Kennita Malarkey, David TI Comparison of Current Technologies for Capturing Photomicrographs for Journal Submission SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Flagler, Norris; Ney, Eli; Johnson, Kennita; Malarkey, David] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P65 BP 171 EP 171 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900084 ER PT J AU Flagler, N Ney, E Mahler, B Malarkey, D AF Flagler, Norris Ney, Eli Mahler, Beth Malarkey, David TI Publication Images: To Adjust or Not to Adjust SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Flagler, Norris; Ney, Eli; Malarkey, David] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Mahler, Beth] Expt Pathol Labs Inc, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2008 VL 36 IS 1 MA P74 BP 174 EP 174 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900093 ER PT J AU Stern, ST McNeil, SE AF Stern, Stephan T. McNeil, Scott E. TI Nanotechnology safety concerns revisited SO TOXICOLOGICAL SCIENCES LA English DT Review DE nanotechnology; nanomaterials; nanoparticles; ultrafines; particle toxicology; safety evaluation ID WALLED-CARBON-NANOTUBES; TITANIUM-DIOXIDE PARTICLES; IN-VIVO EVALUATION; INDUCE OXIDATIVE STRESS; MACROPHAGE CELL-LINE; ULTRAFINE PARTICLES; PULMONARY TOXICITY; FULLERENE C-60; QUANTUM DOTS; POLYMERIC NANOPARTICLES AB Nanotechnology is an emerging science involving manipulation of matter at the nanometer scale. Due to concerns over nanomaterial risks, there has been a dramatic increase in focused safety research. The present review provides a summary of these published findings, identifying areas of agreement and discordance with regard to: (1) the potential for nanomaterial exposure, (2) the relative hazard nanomaterials pose to humans and the environment, and (3) the present deficits in our understanding of risk. Special attention is paid to study design and methodologies, offering valuable insight into the complexities encountered with nanomaterial safety assessment. Recent data highlight the impact of surface characteristics on nanomaterial biocompatibility and point to the inadequacy of the current size-dependent mechanistic paradigms, with nanoscale materials lacking unique or characteristic toxicity profiles. The available data support the ability of the lung, gastrointestinal tract, and skin to act as a significant barrier to the systemic exposure of many nanomaterials. Furthermore, the acute systemic toxicity of many nanomaterials appear to be low. By contrast, the potential pulmonary toxicity of certain nanomaterials, such as carbon nanotubes, is significant, requiring a better understanding of exposure to further evaluate their risk. While these findings arrive at an overall picture of material-specific rather than nanogeneralized risk, any conclusions should clearly be tempered by the fact that nanomaterial safety data are limited. Until such time as the exposures, hazards, and environmental life cycle of nanornaterials have been more clearly defined, cautious development and implementation of nanotechnology is the most prudent course. C1 [Stern, Stephan T.; McNeil, Scott E.] SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, NCI Frederick, Frederick, MD 21702 USA. RP Stern, ST (reprint author), SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, NCI Frederick, Frederick, MD 21702 USA. EM sternstephan@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400] NR 165 TC 271 Z9 288 U1 10 U2 142 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2008 VL 101 IS 1 BP 4 EP 21 DI 10.1093/toxsci/kfm169 PG 18 WC Toxicology SC Toxicology GA 242HY UT WOS:000251717400002 PM 17602205 ER PT J AU Yang, Q Nagano, T Shah, Y Cheung, C Ito, S Gonzalez, FJ AF Yang, Qian Nagano, Tomokazu Shah, Yatrik Cheung, Connie Ito, Shinji Gonzalez, Frank J. TI The PPAR alpha-humanized mouse: A model to investigate species differences in liver toxicity mediated by PPAR alpha SO TOXICOLOGICAL SCIENCES LA English DT Article DE humanized; PAC; PPAR alpha; hepatomegaly; peroxisome proliferators ID PROLIFERATOR-ACTIVATED-RECEPTOR; GENE-EXPRESSION CHANGES; PEROXISOME PROLIFERATORS; HEPATOCELLULAR PROLIFERATION; TRIGLYCERIDE-METABOLISM; AGONIST CIPROFIBRATE; MICROARRAY ANALYSIS; MICE; CLOFIBRATE; HEPATOCARCINOGENESIS AB To determine the impact of the species difference between rodents and humans in response to peroxisome proliferators (PPs) mediated by peroxisome proliferator-activated receptor (PPAR)alpha, PPAR alpha-humanized transgenic mice were generated using a P1 phage artificial chromosome (PAC) genomic clone bred onto a ppar alpha-null mouse background, designated hPPAR alpha(PAC). In hPPAR alpha(PAC) mice, the human PPAR alpha gene is expressed in tissues with high fatty acid catabolism and induced upon fasting, similar to mouse PPAR alpha in wild-type (Wt) mice. Upon treatment with the PP fenofibrate, hPPAR alpha(PAC) mice exhibited responses similar to Wt mice, including peroxisome proliferation, lowering of serum triglycerides, and induction of PPAR alpha target genes encoding enzymes involved in fatty acid metabolism in liver, kidney, and heart, suggesting that human PPAR alpha (hPPAR alpha) functions in the same manner as mouse PPAR alpha in regulating fatty acid metabolism and lowering serum triglycerides. However, in contrast to Wt mice, treatment of hPPAR alpha(PAC) mice with fenofibrate did not cause significant hepatomegaly and hepatocyte proliferation, thus indicating that the mechanisms by which PPAR alpha affects lipid metabolism are distinct from the hepatocyte proliferation response, the latter of which is only induced by mouse PPAR alpha. In addition, a differential regulation of several genes, including the oncogenic let-7C miRNA by PPs, was observed between Wt and hPPAR alpha(PAC) mice that may contribute to the inherent difference between mouse and human PPAR alpha in activation of hepatocellular proliferation. The hPPAR alpha(PAC) mouse model provides an in vivo platform to investigate the species difference mediated by PPAR alpha and an ideal model for human risk assessment PPs exposure. C1 [Yang, Qian; Nagano, Tomokazu; Shah, Yatrik; Cheung, Connie; Ito, Shinji; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS [Z01 BC005561-19] NR 36 TC 81 Z9 85 U1 3 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2008 VL 101 IS 1 BP 132 EP 139 DI 10.1093/toxsci/kfm206 PG 8 WC Toxicology SC Toxicology GA 242HY UT WOS:000251717400012 PM 17690133 ER PT J AU Ouimet, MC Morton, BGS Noelcke, EA Williams, AF Leaf, WA Preusser, DF Hartos, JL AF Ouimet, Marie Claude Morton, Bruce G. Simons Noelcke, Elizabeth A. Williams, Allan F. Leaf, William A. Preusser, David F. Hartos, Jessica L. TI Perceived Risk and Other Predictors and Correlates of Teenagers' Safety Belt Use During the First Year of Licensure SO TRAFFIC INJURY PREVENTION LA English DT Article DE Protection Motivation Theory; Risk Perception; Seat Belt; Adolescent ID HIGH-SCHOOL-STUDENTS; PROTECTION MOTIVATION THEORY; SEAT-BELTS; DRIVERS; PASSENGERS; PERCEPTION; BEHAVIOR; USAGE; INTERVENTION; ADOLESCENTS AB Objectives. Teenagers have the lowest rate of safety belt use and the highest crash rate compared to other age groups. Past studies on teenagers' belt use have mostly been cross-sectional. The first goals of this study were to examine, at licensure, teenagers' and parents' perceptions of risk of crash/injury for newly licensed teenagers when driving unbelted and teenagers' perceived and parents' intended consequences for safety belt rule violations. In addition, the comparability of these variables to other risky driving behaviors was explored. The second goal was to evaluate the importance of these variables in the prediction of teenagers' belt use during the first year of licensure, relative to other factors related to belt use, including demographics and substance use. Methods. More than 2,000 parent-teenager dyads were interviewed by telephone, parents at permit and licensure and teenagers at permit, licensure, and 3, 6, and 12 months after licensure. Results. Approximately a third of the teenagers reported at least once at 3, 6, or 12 months post-licensure not always using their safety belt in the past week. At licensure, participants' perceived risk of safety belt non-use was high and ranked among the behaviors most related to crash/injury for newly licensed teenagers, behind driving under the influence of alcohol or drugs. Parent-imposed consequences for safety belt rule violations were not as highly rated as parent-imposed consequences for driving under the influence of alcohol or drugs. Sequential logistic regression modeled the relationship between safety belt use and perceived risk and consequences of non-use, as well as other prospective predictors assessed at permit and licensure, and driving correlates measured after licensure. Teenagers' extreme perceived risk and parents' intended sure consequences for non-use were significant prospective predictors of regular use during the first year of licensure. Other significant predictors and correlates were race ( White), high school grade average of "A," not smoking cigarettes, driving a passenger vehicle, and never receiving a traffic citation or engaging in risky driving behaviors, including driving under the influence of alcohol or drugs and running a red light. Conclusions. While the effect size was small for perceived risk of non-use, it is amodifiable factor and focused intervention contrived to enhance perceived risk could increase teenagers' belt use. Perceived risk is discussed as a target for intervention in relation to the Protection Motivation Theory. This theory appears helpful in guiding future research into the modifiable factors studied here as well as other factors, including perceived rewards and costs associated with non-use. C1 [Ouimet, Marie Claude; Morton, Bruce G. Simons; Noelcke, Elizabeth A.] NICHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. [Leaf, William A.; Preusser, David F.] Preusser Res Grp Inc, Trumbull, CT USA. [Hartos, Jessica L.] Univ N Carolina, Charlotte, NC 28223 USA. RP Ouimet, MC (reprint author), NICHHD, 6100 Bldg,Room 7B13 MSC 7510, Bethesda, MD 20892 USA. EM ouimetm@mail.nih.gov FU National Institute of Child Health and Human Development FX This research was supported by the Intramural Research Program of the National Institute of Child Health and Human Development. A research postdoctoral fellowship from the Fonds quebecois de la recherche sur la societe et la culture [Quebec Research Funds on Society and Culture] was awarded to the first author. NR 55 TC 14 Z9 15 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1538-9588 J9 TRAFFIC INJ PREV JI Traffic Inj. Prev. PY 2008 VL 9 IS 1 BP 1 EP 10 DI 10.1080/15389580701638793 PG 10 WC Public, Environmental & Occupational Health; Transportation SC Public, Environmental & Occupational Health; Transportation GA 383XE UT WOS:000261706900001 PM 18338289 ER PT J AU Brown, TG Ouimet, MC Nadeau, L Lepage, M Tremblay, J Dongier, M Kin, NMKNY AF Brown, Thomas G. Ouimet, Marie Claude Nadeau, Louise Lepage, Martin Tremblay, Jacques Dongier, Maurice Kin, N. M. K. Ng Ying TI DUI Offenders Who Delay Relicensing: A Quantitative and Qualitative Investigation SO TRAFFIC INJURY PREVENTION LA English DT Article DE Driving Under the Influence; DUI; Recidivism; Alcohol; Assessment; Compliance ID COGNITIVE IMPAIRMENT; TIMELINE FOLLOWBACK; DRINKING DRIVERS; SUBSTANCE-ABUSE; ALCOHOL; INTERVENTIONS; RELIABILITY; VALIDITY; PROGRAM; QUESTIONNAIRE AB Objectives. As in many jurisdictions, individuals convicted of driving under the influence ( DUI) in the province of Quebec are mandated to relicensing programs, which include obligatory participation in intervention programs. However, prolonged delay in relicensing is widespread, potentially contributing to unlicensed driving, untreated substance misuse problems, and drink-driving risk. Information about the characteristics of DUI offenders who delay relicensing (DR) is sparse. This investigation compares the characteristics of DR offenders with those offenders who do not delay (NoDR). In addition, the rationales of DR offenders for delaying relicensing are explored qualitatively. Methods. Two studies were conducted to explore the characteristics of DR offenders. In Study 1, DR offenders (n = 46) were compared to NoDR offenders (n = 74) on multidimensional measures of psychosocial functioning, driving behavior, substance use, and psychological and neurocognitive characteristics. In Study 2, a qualitative examination of 20 DR offenders' reasons underlying delayed relicensing was undertaken, with verbatims content analyzed to identify major themes. A questionnaire, based upon this preliminary analysis, was then administered to another sample of DR participants (N = 37) to appraise and confirm thematic comprehensiveness. Results. The main findings of Study 1 were that, compared to NoDR offenders, DR offenders had more past DUI convictions, were at greater risk for drink driving per kilometer ( km) driven, were more likely to have received substance abuse treatment, and exhibited indices of poorer neurocognitive performance in visual memory and behavioral inhibition domains. No group differences were uncovered on substance use measures. The findings of Study 2 revealed that the expense of participation, availability of alternate transportation, lack of interest, and no access to a vehicle were the most frequent explanations for delayed relicensing. Conclusions. Overall, these findings suggest that both individual and contextual factors influence timely fulfillment of relicensing requirements. While the cost of relicensing may succeed in removing some offenders from the road, it may also be a barrier for others at risk for drink driving, preventing exposure to needed intervention programs. Reducing this barrier may need to be weighted against the risks of relicensing more DUI offenders. Neurocognitive factors may need to be taken into account to not only decrease delay in relicensing but also increase the benefits from participation in interventions that are part of current relicensing programs. C1 [Brown, Thomas G.; Ouimet, Marie Claude; Lepage, Martin; Tremblay, Jacques; Dongier, Maurice; Kin, N. M. K. Ng Ying] Douglas Hosp, Res Ctr, Montreal, PQ H4H 1R3, Canada. [Brown, Thomas G.; Lepage, Martin; Tremblay, Jacques; Dongier, Maurice; Kin, N. M. K. Ng Ying] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Brown, Thomas G.] Pavillon Foster Addicat Rehabil Ctr, St Philippe Laprairie, PQ, Canada. [Ouimet, Marie Claude] NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. [Nadeau, Louise] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. RP Brown, TG (reprint author), Douglas Hosp, Res Ctr, 6875 LaSalle Blvd,Perry 4109, Montreal, PQ H4H 1R3, Canada. EM thomas.brown@mcgill.ca FU Fonds de recherche sur la nature et les technologies [Research funds on nature and technologies]; Ministere des Transports du Quebec [Quebec Ministry of Transport]; Societe de l'assurance automobile du Quebec [SAAQ; Quebec Licensing and Insurance Bureau]; Canadian Safety Council,; Conseil Quebecois de la Recherche Sociale [Quebec Social Research Council] FX The authors would like to acknowledge the exemplary collaboration of Lyne Vezina and Andree Brassard of the Quebec Licensing and Insurance Bureau, Candide Beaumont of the Federation quebecoise des centres de readaptation pour personnes alcooliques et autres toxicomanes [Quebec Federation of Addiction Treatment Centers], as well as the efforts of Lucie Legault in the management and oversight of the study protocol. NR 48 TC 7 Z9 7 U1 3 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1538-9588 J9 TRAFFIC INJ PREV JI Traffic Inj. Prev. PY 2008 VL 9 IS 2 BP 109 EP 118 DI 10.1080/15389580801907908 PG 10 WC Public, Environmental & Occupational Health; Transportation SC Public, Environmental & Occupational Health; Transportation GA 387DC UT WOS:000261930900004 PM 18398773 ER PT B AU Adams, JP Robinson, RA Dudek, SM AF Adams, J. Paige Robinson, Rachel A. Dudek, Serena M. BE Dudek, SM TI Role of action potentials in regulating gene transcription: Relevance to LTP SO TRANSCRIPTIONAL REGULATION BY NEURONAL ACTIVITY: TO THE NUCLEUS AND BACK LA English DT Proceedings Paper CT 35th Annual Meeting of the Society-for-Neuroscience CY NOV 12-16, 2005 CL Washington, DC SP Soc Neurosci ID LONG-TERM POTENTIATION; IMMEDIATE-EARLY GENE; ACTIVATED PROTEIN-KINASE; NMDA RECEPTOR ACTIVATION; CA1 PYRAMIDAL NEURONS; RAT DENTATE GYRUS; LATE-PHASE; HIPPOCAMPAL-NEURONS; MESSENGER-RNA; SYNAPTIC PLASTICITY AB The late phase of Long Term Potentiation (LTP) appears to require transcription, but how the nucleus is informed remains unknown. We propose that calcium elevation from multiple action potentials serves as the signal rather than an NMDA receptor-dependent signal transported from synapses. We find that NMDA receptor antagonists interfere with action potential generation and thus do not resolve the issue. Pharmacologic restoration of action potentials in the presence of NMDA receptor antagonists shows that ERK activation, transcription factor binding, and arc gene expression, previously all shown or thought to be NMDA receptor dependent, are maintained. These data demonstrate that types of signaling in the nucleus, previously attributed to NMDA-receptor dependent synapse-to-nucleus signals, can be initiated by action potentials. Action potential-mediated calcium increases can provide a fast and effective signal in the nucleus that may be an important factor in LTP consolidation. C1 [Adams, J. Paige; Robinson, Rachel A.; Dudek, Serena M.] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Adams, JP (reprint author), NIEHS, Neurobiol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. RI yu, yan/C-2322-2012; OI Dudek, Serena M./0000-0003-4094-8368 NR 66 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-73608-2 PY 2008 BP 91 EP 110 DI 10.1007/978-0-387-73609-9_5 PG 20 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA BGY30 UT WOS:000251315700005 ER PT J AU Kirimlioglu, H Ecevit, A Yilmaz, S Kirimlioglu, V Karabulut, AB AF Kirimlioglu, H. Ecevit, A. Yilmaz, S. Kirimlioglu, V. Karabulut, A. Bay TI Effect of resveratrol and melatonin on oxidative stress enzymes, regeneration, and hepatocyte ultrastructure in rats subjected to 70% partial hepatectomy SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Annual Meeting of the Turkish-Transplantation-Society CY JUL 04-06, 2007 CL Ankara, TURKEY SP Turkish Transplantat Soc ID BREAST-CANCER CELLS; ACID INDUCES APOPTOSIS; LIPID-PEROXIDATION; LIVER-INJURY; MICE; POLYPHENOLS; REGIMEN; TUMOR AB Aim. We sought to compare the antioxidant effects of resveratrol (R) and melatonin (M) after 70% partial hepatectomy (PH) as evidenced by ultrastructural alterations and effects on hepatocyte proliferation and apoptosis. Methods. Twenty-six male Wistar albino rats were randomized into four groups: group A (n = 8) resveratrol (R); group B (n = 8) melatonin (M); group C (n = 5) control PH; group D (n = 5) sham operated animals. The rats that received either R or M were sacrificed a week after PH. The malondialdehyde, glutathione, glutathione S-transferase, and nitric oxide levels were estimated in liver homogenates. The morphological changes were investigated using light and electron microscopy (EM). Cell proliferation was detected by immunohistochemical staining with monoclonal antibodies to Ki-67. Apoptosis was detected by the transferase-mediated dUTP nick end-labeling method. Results. PH induced hepatic LP, decreased GSH and NO, and inhibited GST activity (P < .05). R and M completely prevented PH-induced lipid peroxidation, decreased hepatic GSH and NO levels (P < .05). The inhibition of GST activity was prevented by R (P < .05), but not with M (P > .05). In the PH group EM showed severe morphological changes: mitochondrial degeneration, vacuoles, lipid droplets, and myelin-like figures. In both the R and M groups, morphological alterations repaired protective effects more prominently in the R group. Ki-67 indices (KI) were increased in the PH group and decreased in both R and M groups (P < .001). In the M group, KI was the lowest, but the difference compared with R was not significant (P > .05). Apoptosis was slightly increased in PH, but in either the R or M groups, apoptosis was intensively increased (P < .001). Increased apoptosis was greatest in the M group and the difference compared with the R group was statistically significant (P < .05). Conclusion. R and M suppressed PH-induced oxidative damage, attenuated proliferation, and stimulated apoptosis. When we compared R and M, R showed more potent antioxidative effects and was morphologically more protective to hepatocytes. Antiproliferative effects of M were more potent. Because of their potent antioxidative effects, R and M can be effective for oxidative damage like ischemia-reperfusion injury; however, because of the adverse effects on proliferation and apoptosis more studies are needed in states in which regeneration is critical. C1 Inonu Univ, Malatya, Turkey. NIH, Res Ctr, Washington, DC USA. RP Kirimlioglu, V (reprint author), PK 89, TR-44100 Malatya, Turkey. EM vkirimlioglu@inonu.edu.tr OI bay karabulut, aysun/0000-0002-7873-2805 NR 24 TC 24 Z9 24 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD JAN-FEB PY 2008 VL 40 IS 1 BP 285 EP 289 DI 10.1016/j.transproceed.2007.11.050 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 263PR UT WOS:000253229500073 PM 18261607 ER PT J AU Lee, SE Klauer, SG Olsen, ECB Simons-Morton, BG Dingus, TA Ramsey, DJ Ouimet, MC AF Lee, Suzanne E. Klauer, Sheila G. Olsen, Erik C. B. Simons-Morton, Bruce G. Dingus, Thomas A. Ramsey, David J. Ouimet, Marie Claude TI Detection of Road Hazards by Novice Teen and Experienced Adult Drivers SO TRANSPORTATION RESEARCH RECORD LA English DT Article ID EYE-MOVEMENT PATTERNS; DRIVING SIMULATOR; RISK PERCEPTION; EVALUATE; AWARENESS; CRASH AB Previous laboratory and simulator research has indicated that hazard detection skills and abilities are less developed among novice drivers compared with experienced adult drivers. Novices tend to miss some relevant cues and may be less able to process important elements in the environment while driving. It was hypothesized that novices would have lower hazard detection skills and would react less appropriately to hazards than older and more experienced drivers. Three hazard perception scenarios were simulated on a test track, and data were collected on newly licensed teen drivers (within 2 weeks of licensure) and a comparison group of adults. The scenarios included a hidden stop sign, hidden pedestrian, and hidden pedestrian with lane closure (this last included a text-messaging task). Discrete quantitative performance metrics were evaluated for this analysis, including the following: (a) Did the participant glance at the potential hazard (e.g., stop sign, pedestrian)? (b) Did the participant stop (for the stop sign scenario)? (c) Did the participant show signs of indecision, caution, or awareness (for all hazards)? Significant differences between teen drivers and more experienced adult drivers were found in a combined hazard detection analysis. Results indicated that the adult drivers observed hazards and demonstrated overt recognition of hazards more frequently than the teen drivers did. Results indicated that a large portion of teen drivers failed to disengage from peripheral task engagement in the presence of hazards. The results will be compared with naturalistic data for the same set of drivers to see whether these test track results are predictive of real-world behavior. C1 [Lee, Suzanne E.; Klauer, Sheila G.; Dingus, Thomas A.; Ramsey, David J.] Virginia Polytech Inst & State Univ, Transportat Inst, Blacksburg, VA 24061 USA. [Olsen, Erik C. B.; Simons-Morton, Bruce G.; Ouimet, Marie Claude] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Lee, SE (reprint author), Virginia Polytech Inst & State Univ, Transportat Inst, 3500 Transportat Res Plaza, Blacksburg, VA 24061 USA. EM slee@vtti.vt.edu OI Simons-Morton, Bruce/0000-0003-1099-6617 FU National Institute of Child Health and Human Development FX The research team and authors are indebted to Jennifer Mullen and Dana Condon of VTTI for help in data collection and logistics; Julie Jermeland, Scott Stone, and others at VTTI for help in keeping the research vehicle and roadway operating correctly; Don Fisher of UMass for his help in designing the hazard detection portion of the protocol; and the National Institute of Child Health and Human Development for funding this research and working collaboratively to ensure its success. NR 26 TC 17 Z9 17 U1 3 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0361-1981 J9 TRANSPORT RES REC JI Transp. Res. Record PY 2008 IS 2078 BP 26 EP 32 DI 10.3141/2078-04 PG 7 WC Engineering, Civil; Transportation; Transportation Science & Technology SC Engineering; Transportation GA 391WP UT WOS:000262265200004 ER PT J AU Covell, DG AF Covell, David G. TI Connecting chemosensitivity, gene expression and disease SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID INSTITUTES ANTICANCER SCREEN; CHEMICAL GENETICS; GROWTH-INHIBITION; DRUG DISCOVERY; CANCER GENES; CELL-LINES; IN-VITRO; MECHANISM; PROFILES; IDENTIFICATION AB Omics-based investigations offer potentially powerful readouts that might be useful for probing the underlying biology of normal and diseased states, identifying novel therapeutic targets and proposing relevant markers for designing treatment strategies. A vital component of these investigations involves a systematic analysis of gene expression and chemosensitivity data in the context of disease states and small molecule probes into the function of targets responsible for a disease phenotype. Systematic analysis of chemical and pharmacogenetics data offers a possible means to identify novel, small-molecule, potentially therapeutic, agents that affect the phenotype of a particular target. Elegantly simple in concept, the covariation of genetic and chemosensitivity readouts provide a hypothetical link for relating compounds through genomic expression profiles to underlying biology. C1 NCI, Div Canc Treatment & Diagnosis, Dev Therapeut Program, Screening Technol Branch,Lab Computat Technol, Frederick, MD 21702 USA. RP Covell, DG (reprint author), NCI, Div Canc Treatment & Diagnosis, Dev Therapeut Program, Screening Technol Branch,Lab Computat Technol, Frederick, MD 21702 USA. EM covell@mail.ncifcrfgov NR 55 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JAN PY 2008 VL 29 IS 1 BP 1 EP 5 DI 10.1016/j.tips.2007.10.015 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 256ZG UT WOS:000252767800001 PM 18055024 ER PT J AU Schetter, AJ Leung, SY Sohn, JJ Croce, CM Harris, CC AF Schetter, Aaron J. Leung, Suet Yi Sohn, Jane J. Croce, Carlo M. Harris, Curtis C. TI MicroRNA Expression Profiles Associated with Prognosis and Therapeutic Outcome in Colon Adenocarcinoma SO TUMOR BIOLOGY LA English DT Meeting Abstract CT 36th Meeting of the International-Society-of-Oncology-and-BioMarkers CY OCT 05-09, 2008 CL Tokyo, JAPAN SP Int Soc Oncol & BioMarkers C1 [Schetter, Aaron J.; Sohn, Jane J.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Leung, Suet Yi] Univ Hong Kong, Queen Mary Hosp, Pokfulam, Hong Kong, Peoples R China. [Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PY 2008 VL 29 BP 19 EP 19 PG 1 WC Oncology SC Oncology GA 355RA UT WOS:000259724800023 ER PT J AU Ismail, SAM Fahmy, IA Farrag, SAM AF Ismail, Soher A. Mohammed Fahmy, Iman A. Farrag, Samah Ali Mostafa TI Inverse Correlation of Low Vitamin B-12, Folic Acid and Homocysteine Levels in Diabetic Retinopathy SO TURKISH JOURNAL OF BIOCHEMISTRY-TURK BIYOKIMYA DERGISI LA English DT Article DE Homocysteine; Vitamin B 12; Folic acid; Diabetic retinopathy; Type I diabetes ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SERUM METHYLMALONIC ACID; ENDOTHELIAL-CELL INJURY; PROTEIN-C ACTIVATION; COBALAMIN DEFICIENCY; PLASMA HOMOCYSTEINE; ATHEROGENIC STIMULUS; THROMBOGENIC AGENT; FOLATE-DEFICIENCY; EXPRESSION AB Purpose: Evaluation of total plasma homocysteine, serum vitamin B-12 and folic acid levels in patients with diabetic retinopathy. Materials and Methods: Fifty patients having insulin dependent diabetes mellitus were included and subdivided into 3 groups: Diabetics without retinopathy (n=10), with background retinopathy (n=20), and proliferative retinopathy (n=20). Ten normal subjects served as controls. Plasma total homocysteine levels were measured using HPLC. Serum vitamin B-12 and folic acid levels were carried out using radioimmunoassay technique. Results: There was a statistically significant increase of plasma total homocysteine in diabetics without retinopathy compared to controls, as well as decrease in serum levels of both serum folate and B-12. There was a statistically significant decrease of serum B-12 and folic acid levels and a significant increase of plasma total homocysteine level in diabetics with retinopathy in comparison to those without retinopathy. There was no association between the different degrees of retinopathy studied and plasma total homocysteine concentrations, nor serum B-12 and folic acid concentrations. Conclusion: Diabetic patients with retinopathy are most prone to develop an increase in plasma total homocysteine which may be caused by a deficiency of both blood folate and vitamin B-12 concentrations. This finding directs physicians to the benefit of recommending the use of those vitamins as replacement therapy in diabetics to prevent future atherogenic processes and diabetic complications due to hyperhomocysteinemia. C1 [Ismail, Soher A. Mohammed] Res Inst Ophthalmol, Dept Biochem, Giza, Egypt. [Farrag, Samah Ali Mostafa] Natl Canc Inst, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Ismail, SAM (reprint author), Ophthalmol Res Ctr, Cairo, Egypt. EM nahedw7@hotmail.com NR 48 TC 0 Z9 0 U1 0 U2 0 PU TURKISH BIOCHEM SOC PI ANKARA PA HIRFANLI SOKAK BANU, APT 9-3 GAZIOSMANPASA, ANKARA, 06700, TURKEY SN 0250-4685 J9 TURK J BIOCHEM JI Turk. J. Biochem. PY 2008 VL 33 IS 1 BP 14 EP 18 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 367VP UT WOS:000260581000003 ER PT J AU Singhal, AB Koroshetz, WJ Caplan, LR AF Singhal, Aneesh B. Koroshetz, Walter J. Caplan, Louis R. BE Caplan, LR TI REVERSIBLE CEREBRAL VASOCONSTRICTION SYNDROMES SO UNCOMMON CAUSES OF STROKE, 2ND EDITION LA English DT Article; Book Chapter ID CENTRAL-NERVOUS-SYSTEM; CALL-FLEMING-SYNDROME; POSTERIOR LEUKOENCEPHALOPATHY SYNDROME; GUILLAIN-BARRE-SYNDROME; THUNDERCLAP HEADACHE; INTRACRANIAL HEMORRHAGE; INTRACEREBRAL HEMORRHAGE; CAROTID-ENDARTERECTOMY; TRANSCRANIAL DOPPLER; MIGRAINOUS VASOSPASM C1 [Singhal, Aneesh B.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA. [Caplan, Louis R.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Singhal, AB (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 121 TC 5 Z9 5 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-87437-3 PY 2008 BP 505 EP 514 DI 10.1017/CBO9780511544897.068 D2 10.1017/CBO9780511544897 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BDP59 UT WOS:000314314600068 ER PT S AU Quaia, C Shan, XY Tian, J Ying, H Optican, LM Walker, M Tamargo, R Zee, DS AF Quaia, Christian Shan, Xiaoyan Tian, Jing Ying, Howard Optican, Lance M. Walker, Mark Tamargo, Rafael Zee, David S. BE Kennard, C Leigh, RJ TI Acute superior oblique palsy in the monkey: effects of viewing conditions on ocular alignment and modelling of the ocular motor plant SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE superior oblique palsy; strabismus; eye plant; ocular motor; adaptation; eye movements ID TROCHLEAR NERVE PALSY; HEAD-TILT TEST; OCULOMOTOR PLANT; MUSCLE PATHS; POSITION; PULLEYS; LAW AB We investigated the immediate and long-term changes in static eye alignment with acute superior oblique palsy (SOP) in the monkey. When the paretic eye was patched immediately after the lesion for 6-9 days, vertical alignment slowly improved. When the patch was removed and binocular viewing was allowed, alignment slowly worsened. In contrast when a monkey was not patched immediately after the lesion vertical alignment did not improve. We also show that a model of the eye plant can reproduce the observed acute deficit induced by SOP, but only by abandoning Robinson's symmetric simplification of the reciprocal innervation relationship within pairs of agonist-antagonist muscles. The model also demonstrated that physiologic variability in orbital geometry can have a large impact on SOP deficits. C1 [Shan, Xiaoyan; Tian, Jing; Ying, Howard; Tamargo, Rafael; Zee, David S.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. [Optican, Lance M.] NEI, Sensorimotor Res Lab, NIH, DHHS, Bethesda, MD 20892 USA. [Walker, Mark] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Walker, Mark] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Walker, Mark] Case Western Reserve Univ, Dept Neurol, Daroff DellOsso Lab, Vet Affairs Med Ctr, Cleveland, OH 44106 USA. [Walker, Mark] Case Western Reserve Univ, Univ Hosp, Cleveland, OH 44106 USA. RP Zee, DS (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM dzee@dizzy.med.jhu.edu NR 26 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 47 EP 52 DI 10.1016/S0079-6123(08)00607-9 PG 6 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400008 PM 18718281 ER PT S AU Optican, LM AF Optican, Lance M. BE Kennard, C Leigh, RJ TI The role of omnipause neurons: why glycine? SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE glycine; burst neurons; brainstem; saccades ID SACCADIC EYE-MOVEMENTS; PONTINE RETICULAR-FORMATION; OCULOMOTOR SYSTEM; BURST NEURONS; PAUSE NEURONS; ALERT CATS; NUCLEUS; MONKEY; NEUROTRANSMITTER; SYNAPSES AB The anatomy and neurophysiology of the saccadic eye movement system have been well studied, but the roles of certain key neurons in this system are not fully appreciated. Important clues about the functional interactions in the saccadic system can be gleaned from the histochemistry of different saccadic neurons. The most prominent inhibitory neurons in the circuit are the omnidirectional pause neurons (OPN), which inhibit the premotor burst neurons that drive the eye. Most inhibitory neurons in the brain transmit gamma-aminobutyric acid (GABA), but OPN transmit glycine (Gly). It is interesting to ask whether the saccadic system would work any differently if OPN were GABA-ergic. Gly and GABA receptors both provide a channel for a hyperpolarizing Cl(-) current that inhibits its target neuron. Depolarizing currents that excite the neurons come through several channels, including the NMDA receptor (NMDAR). The NMDAR is unique among receptors in that it has active sites for two different neurotransmitters, glutamate (Glu) and Gly. Gly is a co-agonist that acts to amplify the current produced by Glu. We have proposed a model of the saccadic brain stem circuitry that exploits this dual role of Gly to produce both inhibition of the saccadic circuit during fixation, and to increase its responsiveness, or gain, during movements. This suggests that OPNs act more as a regulator of the saccadic circuit's gain, rather than as a gate for allowing saccades. We propose a new hypothesis: the OPNs play a general role as a modulator of arousal in orienting subsystems, such as saccades, pursuit, head movements, etc. C1 [Optican, Lance M.] NEI, Sensorimotor Res Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Optican, LM (reprint author), NEI, Sensorimotor Res Lab, NIH, DHHS, Bldg 10, Bethesda, MD 20892 USA. EM LanceOptican@nih.gov FU NEI FX This work was supported by the Intramural Research Program of the NEI. NR 22 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 115 EP 121 DI 10.1016/S0079-6123(08)00615-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400016 PM 18718289 ER PT S AU Ramat, S Leigh, RJ Zee, DS Shaikh, AG Optican, LM AF Ramat, S. Leigh, R. J. Zee, D. S. Shaikh, A. G. Optican, L. M. BE Kennard, C Leigh, RJ TI Applying saccade models to account for oscillations SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE saccadic system; saccade models; saccadic Oscillations ID EXCITATORY BURST NEURONS; ALERT SQUIRREL-MONKEY; EYE-MOVEMENTS; SUPERIOR COLLICULUS; OCULAR OSCILLATIONS; OMNIPAUSE NEURONS; PHYSIOLOGY; DISORDERS; PATHWAYS; ANATOMY AB Saccadic oscillations are unwanted back-to-back saccades occurring one upon the other that produce a high-frequency oscillation of the eyes (usually 15-30 Hz). These may occur transiently in normal subjects, for example, around the orthogonal axis of a purely horizontal or vertical saccade, during combined saccade-vergence gaze shifts or during blinks. Some subjects may produce saccadic oscillations at will, usually with convergence. Pathological, involuntary saccadic oscillations such as flutter and opsoclonus are prominent in certain diseases. Our recent mathematical model of the premotor circuit for generating saccades includes brainstem burst neurons in the paramedian pontine reticular formation (PPRF), which show the physiological phenomenon of post-inhibitory rebound (PIR). This model makes saccadic oscillations because of the positive feedback among excitatory and inhibitory burst neurons. Here we review our recent findings and hypotheses and show how they may be reproduced using our lumped model of the saccadic premotor circuitry by reducing the inhibitory efficacy of omnipause neurons. C1 [Ramat, S.] Univ Pavia, Dipartimento Informat & Sistemist, I-27100 Pavia, Italy. [Leigh, R. J.] Case Western Reserve Univ, Dept Neurol, Vet Affairs Med Ctr, Dept Biomed Engn,Daroff DellOsso Lab, Cleveland, OH 44106 USA. [Leigh, R. J.] Case Western Reserve Univ, Univ Hosp, Cleveland, OH 44106 USA. [Zee, D. S.; Shaikh, A. G.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Optican, L. M.] NEI, Sensorimotor Res Lab, IRP, Bethesda, MD 20892 USA. [Zee, D. S.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. RP Ramat, S (reprint author), Univ Pavia, Dipartimento Informat & Sistemist, I-27100 Pavia, Italy. EM stefano.ramat@unipv.it RI Ramat, Stefano/E-6495-2011 OI Ramat, Stefano/0000-0001-5932-186X NR 24 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 123 EP 130 DI 10.1016/S0079-6123(08)00616-X PG 8 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400017 PM 18718290 ER PT S AU Hong, S Leigh, RJ Zee, DS Optican, LM AF Hong, Simon Leigh, R. John Zee, David S. Optican, Lance M. BE Kennard, C Leigh, RJ TI Inferior olive hypertrophy and cerebellar learning are both needed to explain ocular oscillations in oculopalatal tremor SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE Purkinje cell; interneuron; interaction; waveform; mGluR; classical conditioning; gap junction ID PURKINJE-CELL DENDRITES; RECEPTOR; RABBITS; PROJECTIONS; MEFLOQUINE; NEURONS; MEMORY AB A new model of cerebellar learning explains how the cerebellum can generate arbitrary output waveforms to adjust output timing in the classical delay conditioning. This model can also reproduce the low frequency ocular oscillations seen in oculopalatal tremor (OPT). A novel circuit in the cerebellum uses both interneurons (INs) and Purkinje cells (PC) to control timing. Brain lesions that cause OPT give rise to hypertrophy of the inferior olive (IO) and an increase in conductance through gap junctions among IO neurons. When our model is changed in this way, the heavily coupled IO becomes an oscillator and generates synchronous spike trains at 1-2 Hz. These synchronized spikes do not produce the large amplitude, aperiodic waveforms of OPT. However, the synchronized IO signal goes to the cerebellar cortex (flocculus) directly, on climbing fibres, and indirectly, on mossy fibres from the vestibular nuclei. This creates a pathological association between the IO pulse trains on mossy and climbing fibres in PC. Variable pendular ocular oscillations emerged from the cerebellum model after learning this association. Since electrotonic coupling of IO cells depends on connexin proteins, drugs that block gap junctions, such as antimalarial agents, might provide a novel therapy for OPT. C1 [Hong, Simon; Optican, Lance M.] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. [Leigh, R. John] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Leigh, R. John] Vet Affairs Med Ctr, Cleveland, OH USA. [Zee, David S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Optican, LM (reprint author), NEI, Sensorimotor Res Lab, Bldg 10, Bethesda, MD 20892 USA. EM LanceOptican@nih.gov NR 20 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 219 EP 226 DI 10.1016/S0079-6123(08)00631-6 PG 8 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400032 PM 18718305 ER PT S AU Liao, K Hong, S Zee, DS Optican, LM Leigh, RJ AF Liao, Ke Hong, Simon Zee, David S. Optican, Lance M. Leigh, R. J. BE Kennard, C Leigh, RJ TI Impulsive head rotation resets oculopalatal tremor: examination of a model SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE inferior olive; wavelets; vestibulo-ocular reflex; gap junctions; clonazepam; memantine ID PALATAL TREMOR; MYOCLONUS; ATAXIA AB We have described a neuromimetic model of the interaction between the inferior olive (IO) and the cerebellum that accounts for symptomatic oculopalatal tremor (OPT), a disorder characterized by oscillations of the eyes (nystagmus), palate and other branchial muscles. OPT develops months after some brainstem strokes, in association with hypertrophic degeneration of the inferior olivary nucleus (IO). We hypothesized that OPT requires both (1) a pulsatile oscillator created by tighter electrotonic coupling between cells in the IO, and (2) a learned response from the cerebellar cortex that combines with the IO pulses to generate the quasi-pendular oscillations. Since the vestibular nuclei project to both IO and vestibulocerebellum, one prediction of the model is that rapid head rotations could interrupt the oscillator, effectively resetting the timing of the ocular nystagmus. The ocular oscillations in OPT vary in amplitude and phase, making it difficult to determine by Fourier analysis whether head perturbations phase-shift the nystagmus. We applied complex wavelet analysis to data from four patients with OPT and checked whether vestibular stimuli induced a change in phase of the nystagmus. First we calculated a threshold for the spontaneous rate of change of phase of OPT by comparing many segments of nystagmus waveform with their time-shifted versions, bootstrapping these arrays, and computing 95% prediction intervals for each patient. Then we compared the rate of change of phase due to each head perturbation with the threshold for that patient. To minimize the effects of the head perturbation itself on the wavelet analysis, we measured effects in a plane orthogonal to the head rotation, e. g., effects of horizontal head rotations on the torsional component of OPT. In all four patients, the rate of change of phase shift increased sharply at the time of the head perturbation, and in three the change was judged to be statistically significant. Thus, the experimental tests supported the prediction of our model for OPT. C1 [Liao, Ke; Leigh, R. J.] Case Western Reserve Univ, Daroff Dell Osso Lab, Vet Affairs Med Ctr, Cleveland, OH 44106 USA. [Liao, Ke; Leigh, R. J.] Case Western Reserve Univ, Dept Neurol, Univ Hosp, Cleveland, OH 44106 USA. [Hong, Simon; Optican, Lance M.] NEI, Sensorimotor Res Lab, NIH, DHHS, Bethesda, MD 20892 USA. [Zee, David S.] Johns Hopkins Univ, Baltimore, MD USA. RP Leigh, RJ (reprint author), Case Western Reserve Univ, Daroff Dell Osso Lab, Vet Affairs Med Ctr, Cleveland, OH 44106 USA. EM rjl4@case.edu; rjl4@case.edu RI liao, ke/B-1453-2010 FU NIH [EY06717]; Office of Research and Department of Veterans Affairs; Evenor Armington Fund; Intramural Division of the National Eye Institute, NIH, DHHS FX This work is supported by NIH grant EY06717; the Office of Research and Department of Veterans Affairs; Evenor Armington Fund; Intramural Division of the National Eye Institute, NIH, DHHS. NR 17 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 227 EP 234 DI 10.1016/S0079-6123(08)00632-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400033 PM 18718306 ER PT S AU Sheliga, BM FitzGibbon, EJ Miles, FA AF Sheliga, B. M. FitzGibbon, E. J. Miles, F. A. BE Kennard, C Leigh, RJ TI Human ocular following: evidence that responses to large-field stimuli are limited by local and global inhibitory influences SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE ocular following response (OFR); response normalization; surround inhibition ID VERGENCE EYE-MOVEMENTS; VISUAL AREA MT; SPATIAL SUMMATION; MOTION; NORMALIZATION; CORTEX; DEPENDENCE; NEURONS; MACAQUE; ENERGY AB Large-field visual motion elicits tracking eye movements at ultra-short latency, often termed ocular following responses (OFRs). We recorded the initial OFRs of three human subjects when vertical sine-wave gratings were subject to horizontal motion in the form of successive 1/4-wavelength steps. The gratings could occupy the full screen (45 degrees wide, 30 degrees high) or a number of horizontal strips, each 1 degrees high and extending the full width of the display. These strips were always equally spaced vertically. In a first experiment, the gratings always had a contrast of 32%. Increasing the number of strips could reduce the response latency by up to 20 ms, so the magnitude of the initial OFRs was estimated from the change in eye position over the initial open-loop period measured with respect to response onset. A single (centred) strip (covering 3.3% of the screen) always elicited robust OFRs, and three strips (10% coverage) were sufficient to elicit the maximum OFR. Increasing the number of strips to 15 (50% coverage) had little impact, i.e., responses had asymptoted, and further increasing the coverage to 100% (full screen image) actually decreased the OFR so that it was now less than that elicited with only one strip. In a second experiment, the contrast of the gratings could be fixed at one of the four levels ranging from 8% to 64%, and the OFR showed essentially the same pattern of dependence on screen coverage except that the lower the contrast, the lower the level at which the response asymptoted. This indicated that the asymptote was not due simply to some upper limit on the magnitude of the eye movement or the underlying motion signals. We postulate that this asymptote is the result of normalization due to global divisive inhibition, which has often been described in visual-motion-selective neurons in the cortex. We further suggest that the decrease in the OFR when the image filled the screen was due to the increased continuity of the gratings which we postulate would favour the local inhibitory surround mechanisms over the central excitatory ones. This study indicates that robust OFRs can be elicited by much smaller motion stimuli than is commonly supposed and that introducing spatial discontinuities can increase the efficacy of the motion stimuli even while decreasing the area stimulated. C1 [Sheliga, B. M.; FitzGibbon, E. J.; Miles, F. A.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Sheliga, BM (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM bms@lsr.nei.nih.gov FU National Eye Institute at the National Institutes of Health FX This research was supported by the intramural programme of the National Eye Institute at the National Institutes of Health. NR 23 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 237 EP 243 DI 10.1016/S0079-6123(08)00633-X PG 7 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400034 PM 18718307 ER PT S AU Rambold, HA Miles, FA AF Rambold, H. A. Miles, F. A. BE Kennard, C Leigh, RJ TI Short-latency disparity vergence eye movements: dependence on the preexisting vergence angle SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE disparity vergence eye movements ID VIEWING DISTANCE; OCULAR RESPONSES; HUMANS; TRANSLATION; SCENE AB We recorded the vergence eye movements that are elicited at ultra-short latencies when binocular disparities are applied to large-field patterns (Busettini, C., Miles, F. A. and Krauzlis, R.J. (1996). J. Neurophysiol., 75: 1392-1410) and determined their dependence on the preexisting vergence angle (PVA). The search coil technique was used to record the movements of both eyes in four healthy subjects (two with presbyopia). Using dichoptic viewing, the two eyes saw identical images each consisting of a fixation cross at the centre of a random-dot pattern in a circular aperture. The subject fixated the crosses and then the images (crosses, random dots, windows) moved horizontally (1.5 degrees/s) in opposite directions so as to bring the eyes to the desired horizontal vergence position without changing the accommodation demand. After a further 800-1200 ms to permit fusion at this new vergence angle (now, the PVA), a disparity step was applied and, 200 ms later, the screen changed to uniform grey, marking the end of the trial. The disparity steps could have one of six magnitudes and four directions (crossed, uncrossed, right-hyper, left-hyper) while the PVA was varied systematically. The horizontal and vertical disparity vergence responses (DVRs) of one of the presbyopes consistently showed robust linear dependence on the PVA (r(2) > 0.96). The horizontal DVRs of the other three subjects showed no sensitivity to the PVA and their vertical DVRs showed only very weak dependence. The experiment was repeated on one of the non-presbyopes after cycloplegia, but the outcome was the same, indicating that the negative findings were not due to the influence of the vergence-accommodation response. Our data indicate that the DVRs can be scaled by the PVA, but most subjects do not show this effect, perhaps because they relied on other distance cues that are uninformative in our experimental situation. C1 [Rambold, H. A.; Miles, F. A.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Rambold, H. A.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. RP Rambold, HA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM ramboldh@nei.nih.gov OI Rambold, Holger/0000-0002-8056-9429 FU Alexander von Humboldt Foundation (Germany); National Eye Institute of the National Institutes of Health FX The authors thank B.M. Sheliga and E. Fitzgibbon for technical and experimental support and B.M. Sheliga, S. Tanabe, and D.S. Zee for taking part in the experiments. This study was supported by the Alexander von Humboldt Foundation (Germany) and the Intramural Program of the National Eye Institute of the National Institutes of Health. NR 16 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 245 EP 251 DI 10.1016/S0079-6123(08)00634-1 PG 7 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400035 PM 18718308 ER PT S AU Hikosaka, O Isoda, M AF Hikosaka, Okihide Isoda, Masaki BE Kennard, C Leigh, RJ TI Brain mechanisms for switching from automatic to controlled eye movements SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE presupplementary motor area; medial frontal cortex; subthalamic nucleus; substantia nigra pars reticulata; basal ganglia; monkeys; saccadic eye movement; habitual action; conscious control; decision-making ID MEDIAL FRONTAL-CORTEX; PRESUPPLEMENTARY MOTOR AREA; SUBTHALAMIC NUCLEUS; SEQUENTIAL-PROCEDURES; NEURONAL-ACTIVITY; BASAL GANGLIA; MONKEY; TASK; COMPETITION; ACTIVATION AB Human behaviour is mostly composed of habitual actions that require little conscious control. Such actions may become invalid if the environment changes, at which point we need to switch behaviour by overcoming habitual actions that are otherwise triggered automatically. It is unclear how the brain controls this type of behavioural switching. Here we show that the presupplementary motor area (pre-SMA) in the medial frontal cortex has a function in switching from automatic to volitionally controlled action. This was demonstrated using colour-matching saccade tasks performed by rhesus monkeys. We found that a group of pre-SMA neurons was selectively activated when subjects successfully switched from a habitual saccade to a controlled alternative saccade. Electrical stimulation in the pre-SMA replaced automatic incorrect saccades with slower correct saccades. A further test suggested that the pre-SMA enabled switching by first suppressing an automatic unwanted saccade and then boosting a controlled desired saccade. Our data suggest that the pre-SMA resolves response conflict so that the desired action can be selected. Possible neuronal circuits through which the pre-SMA might exert its switching functions will be discussed. C1 [Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Isoda, Masaki] RIKEN Brain Sci Inst, Lab Symbol Cognit Dev, Saitama, Japan. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM oh@lsr.nei.nih.gov; isodam@brain.riken.jp FU Intramural NIH HHS [Z01 EY000415-05] NR 24 TC 13 Z9 13 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 375 EP 382 DI 10.1016/S0079-6123(08)00655-9 PG 8 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400056 PM 18718329 ER PT S AU Matsumoto, M Hikosaka, O AF Matsumoto, Masayuki Hikosaka, Okihide BE Kennard, C Leigh, RJ TI Negative motivational control of saccadic eye movement by the lateral habenula SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE reward; lateral habenula; dopamine neuron; saccade; monkey ID REWARD; RAT; CONNECTIONS; NEURONS; COMPLEX; NUCLEI AB Reward is crucial for survival of animals and influences animal behaviours. For example, an approaching behaviour to reward is more frequently and quickly elicited when a big reward is expected than when a small reward is expected. Midbrain dopamine neurons are thought to be crucial for such reward-based control of motor behaviour. Indeed, dopamine neurons are excited by cues predicting reward and inhibited by cues predicting no-reward. These excitatory and inhibitory signals would then be used for enhancing and depressing sensorimotor processing, respectively, in the brain areas targeted by dopamine neurons (e.g., striatum). However, it was unknown which parts of the brain provide dopamine neurons with reward-related signals necessary for their responses. We recently showed evidence that the lateral habenula transmits reward-related signals to dopamine neurons, especially to inhibit dopamine neurons. This recent study suggested that the lateral habenula suppresses less rewarding saccadic eye movements by inhibiting dopamine neurons. In the present review, we first summarize anatomical and functional aspects of the lateral habenula. We will then describe our own study. Finally, we will discuss how the lateral habenula, as well as dopamine neurons, contributes to the reward-based control of saccadic eye movements. C1 [Matsumoto, Masayuki; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM oh@lsr.nei.nih.gov FU Intramural NIH HHS [Z01 EY000415-05] NR 9 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 399 EP 402 DI 10.1016/S0079-6123(08)00658-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400059 PM 18718332 ER PT S AU Rambold, HA Sander, T Sprenger, A Helmchen, C AF Rambold, H. A. Sander, T. Sprenger, A. Helmchen, C. BE Kennard, C Leigh, RJ TI Tracking in 3-D space under natural viewing condition SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE vergence; eye movements; smooth pursuit ID VERGENCE EYE-MOVEMENTS; SMOOTH-PURSUIT; RESPONSES; HUMANS; STEREOPSIS; INITIATION; DISPARITY; SACCADES; STIMULUS; MONKEYS AB To track a small visual target in 3-D space, the two eyes have to move in different directions and/or at different velocities. This tracking might be accomplished by a disjunctive pursuit system, which uses separate motion processing of each individual eye but no disparity signal (hypothesis 1), or by the conjugate pursuit and the vergence system (hypothesis 2). To test the validity of the two hypotheses we recorded eye movements in five healthy human subjects with the scleral search-coil method. A small dim laser stimulus was presented on an earth horizontal platform. A position-ramp stimulus was presented in eight different directions: rightward or leftward, convergence or divergence, or a combination of them. We compared a fusible with an un-fused and a monocular viewing condition to assess whether a disparity signal is needed for 3-D tracking. Fusion was prevented by a vertical prism. We compared the monocular with the prism viewing condition to examine the effect of retinal motion signals of either one or both eyes on the tracking performance in the absence of disparity signals. Results revealed severe impairment of tracking in depth, while tracking in pure horizontal directions remained unaffected during the prism and monocular as compared to the binocular viewing condition. These data support hypothesis 2. C1 [Rambold, H. A.; Sander, T.; Sprenger, A.; Helmchen, C.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Rambold, H. A.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Rambold, HA (reprint author), Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. EM ramboldh@nei.nih.gov RI Sprenger, Andreas/C-7612-2009; OI Sprenger, Andreas/0000-0001-9255-7911; Rambold, Holger/0000-0002-8056-9429 NR 24 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 459 EP 465 DI 10.1016/S0079-6123(08)00667-5 PG 7 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400068 PM 18718341 ER PT S AU Berman, RA Wurtz, RH AF Berman, Rebecca A. Wurtz, Robert H. BE Kennard, C Leigh, RJ TI Exploring the pulvinar path to visual cortex SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE pulvinar; superior colliculus; MT; two visual pathways; monkey visual pathways ID SUPERIOR COLLICULUS; INFERIOR PULVINAR; MACAQUE MONKEY; RHESUS-MONKEY; AREA-MT; PROJECTIONS; ORGANIZATION; THALAMUS AB The primary pathway for visual signals from the retina to cerebral cortex is through the lateral geniculate nucleus of the thalamus to primary visual cortex. A second visual pathway has been postulated to pass through the thalamic pulvinar nucleus and to project to multiple regions of visual cortex. We have explored this second visual pathway using a method that allows us to identify the inputs and outputs of pulvinar neurons. Specifically, we applied microstimulation in the superficial layers of superior colliculus (SC) to test for orthodromic activation of pulvinar neurons receiving input from SC. We also microstimulated the cortical motion area MT and tested for antidromic activation of pulvinar to identify neurons projecting to MT (and to determine the presence of orthodromic input back to pulvinar). In this initial report, we concentrate on two observations. First, we find that there are clusters of neurons in the pulvinar that receive input from SC along with neurons that project to MT or receive input from MT. Second, we find that neurons with input from SC have characteristics of the SC superficial layers: they respond to visual stimuli but do not discharge before saccadic eye movements. Neurons projecting to MT respond similarly to these SC-input neurons, while those receiving input from MT more frequently show directional selectivity as does MT. These findings indicate the visual nature of the signals conveyed in this pathway and shed light on the functional role of the thalamus in a possible second visual pathway. C1 [Berman, Rebecca A.; Wurtz, Robert H.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Berman, RA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM bermanr@nei.nih.gov FU Intramural NIH HHS [Z01 EY000109-28] NR 18 TC 29 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 467 EP 473 DI 10.1016/S0079-6123(08)00668-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400069 PM 18718342 ER PT S AU Rucker, JC Leigh, RJ Optican, LM Keller, EL Buttner-Ennever, JA AF Rucker, Janet C. Leigh, R. John Optican, Lance M. Keller, Edward L. Buettner-Ennever, Jean A. BE Kennard, C Leigh, RJ TI Ocular motor anatomy in a case of interrupted saccades SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE fastigial nucleus; omnipause neurons; burst neurons; latch circuit; brainstem ID PARVALBUMIN; MONKEY AB Saccades normally place the eye on target with one smooth movement. In late-onset Tay-Sachs (LOTS), intrasaccadic transient decelerations occur that may result from (1) premature omnipause neuron (OPN) re-activation due to malfunction of the latch circuit that inhibits OPNs for the duration of the saccade or (2) premature inhibitory burst neuron (IBN) activation due to fastigial nucleus (FN) dysregulation by the dorsal cerebellar vermis. Neuroanatomic analysis of a LOTS brain was performed. Purkinje cells were absent and gliosis of the granular cell layer was present in the dorsal cerebellar vermis. Deep cerebellar nuclei contained large inclusions. IBNs were present with small inclusions. The sample did not contain the complete OPN region; however, neurons in the OPN region contained massive inclusions. Pathologic findings suggest that premature OPN re-activation and/or inappropriate firing of IBNs may be responsible for interrupted saccades in LOTS. Cerebellar clinical dysfunction, lack of saccadic slowing, and significant loss of cerebellar cells suggest that the second cause is more likely. C1 [Rucker, Janet C.] Rush Presbyterian St Lukes Med Ctr, Chicago, IL USA. [Leigh, R. John] Vet Affairs Med Ctr, Daroff DellOsso Lab, Dept Biomed Engn, Dept Neurol, Cleveland, OH USA. [Leigh, R. John] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Optican, Lance M.] NEI, Sensorimotor Res Lab, NIH, DHHS, Bethesda, MD 20892 USA. [Keller, Edward L.] Smith Kettlewell Eye Inst, San Francisco, CA USA. [Buettner-Ennever, Jean A.] Univ Munich, Inst Anat, Munich, Germany. [Leigh, R. John] Case Western Reserve Univ, Univ Hosp, Cleveland, OH 44106 USA. RP Rucker, JC (reprint author), Rush Presbyterian St Lukes Med Ctr, Chicago, IL USA. EM janet_rucker@rush.edu FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs; NIH [EY06717]; Evenor Armington Fund; NEI IRP FX This work was supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs; NIH grant EY06717; the Evenor Armington Fund (R.J.L.); and the NEI IRP. NR 4 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 563 EP 566 DI 10.1016/S0079-6123(08)00680-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400081 PM 18718354 ER PT S AU Optican, LM Rucker, JC Keller, EL Leigh, RJ AF Optican, Lance M. Rucker, Janet C. Keller, Edward L. Leigh, R. John BE Kennard, C Leigh, RJ TI Mechanism of interrupted saccades in patients with late-onset Tay-Sachs disease SO USING EYE MOVEMENTS AS AN EXPERIMENTAL PROBE OF BRAIN FUNCTION - A SYMPOSIUM IN HONOR OF JEAN BUTTNER-ENNEVER SE Progress in Brain Research LA English DT Review CT Symposium on Using Eye Movements as an Experimental Probe of Brain Function held in honor of Jean Buttner Ennever CY DEC 05-06, 2007 CL Imperial College, Charing Cross Hosp Campus, London, ENGLAND HO Imperial College, Charing Cross Hosp Campus DE fastigial nucleus; omnipause neurons; burst neurons; latch circuit AB In late-onset Tay-Sachs disease (LOTS), saccades are interrupted by one or more transient decelerations. Some saccades reaccelerate and continue on before eye velocity reaches zero, even in darkness. Intervals between successive decelerations are not regularly spaced. Peak decelerations of horizontal and vertical components of oblique saccades in LOTS is more synchronous than those in control subjects. We hypothesize that these decelerations are caused by dysregulation of the fastigial nuclei (FN) of the cerebellum, which fire brain stem inhibitory burst neurons (IBNs). C1 [Optican, Lance M.] NEI, Sensorimotor Res Lab, NIH, DHHS, Bethesda, MD 20892 USA. [Rucker, Janet C.] Rush Med Coll, Chicago, IL 60612 USA. [Keller, Edward L.] Smith Kettlewell Eye Res Inst, San Francisco, CA 94115 USA. [Leigh, R. John] Case Western Reserve Univ, Univ Hosp, Cleveland, OH 44106 USA. [Leigh, R. John] Vet Affairs Med Ctr, Daroff Dellosso Lab, Dept Biomed Engn, Dept Neurol, Cleveland, OH USA. [Rucker, Janet C.] Rush Presbyterian St Lukes Med Ctr, Chicago, IL USA. RP Optican, LM (reprint author), NEI, Sensorimotor Res Lab, NIH, DHHS, Bldg 10, Bethesda, MD 20892 USA. EM LanceOptican@nih.gov FU Office of Research and Development, Medical Research Service, Department of Veterans Affairs; National Eye Institute [EY06717, EY08060]; Evenor Armington Fund; Intramural Division of the National Eye Institute, NIH, DHHS FX This research was supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs; National Eye Institute grants EY06717 and EY08060; the Evenor Armington Fund; and the Intramural Division of the National Eye Institute, NIH, DHHS. NR 4 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-53163-6 J9 PROG BRAIN RES PY 2008 VL 171 BP 567 EP 570 DI 10.1016/S0079-6123(08)00681-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA BQC47 UT WOS:000280686400082 PM 18718355 ER PT J AU El Sahly, HM Patel, SM Atmar, RL Long, C Zhou, H Keitel, WA AF El Sahly, H. M. Patel, S. M. Atmar, R. L. Long, C. Zhou, H. Keitel, W. A. TI Phase 1, Double-Blinded, Placebo-Controlled, Dosage-Escalation Study of the Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly SO VACCINE LA English DT Meeting Abstract CT 2nd Vaccine Congress CY DEC 07-09, 2008 CL Boston, MA DE Malaria; Vaccine; Clinical Trial; Phase I C1 [El Sahly, H. M.; Patel, S. M.; Atmar, R. L.; Keitel, W. A.] Baylor Coll Med, Houston, TX 77030 USA. [Long, C.; Zhou, H.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PY 2008 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 480QF UT WOS:000268750600025 ER PT J AU Kubler-Kielb, J Vinogradov, E Mocca, C Schneerson, R Robbins, JB AF Kubler-Kielb, J. Vinogradov, E. Mocca, C. Schneerson, R. Robbins, J. B. TI Shigella sonnei oligosaccharide-protein conjugates SO VACCINE LA English DT Meeting Abstract CT 2nd Vaccine Congress CY DEC 07-09, 2008 CL Boston, MA DE shigella; vaccine; LPS; conjugate C1 [Kubler-Kielb, J.; Mocca, C.; Schneerson, R.; Robbins, J. B.] NIH, Bethesda, MD 20892 USA. [Vinogradov, E.] NRC, Ottawa, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PY 2008 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 480QF UT WOS:000268750600155 ER PT J AU Kwissa, M Amara, RR Robinson, HL Moss, B Alkan, S Pulendran, B AF Kwissa, M. Amara, R. R. Robinson, H. L. Moss, B. Alkan, S. Pulendran, B. TI Adjuvanting a DNA Vaccine With a TLR9 Ligand Plus FIt3 Ligand Results in Enhanced Cellular Immunity Against the Simian Immunodeficiency Virus SO VACCINE LA English DT Meeting Abstract CT 2nd Vaccine Congress CY DEC 07-09, 2008 CL Boston, MA DE Toll Like Receptors (TLR); Dendritic Cells; HIV; CpG C1 [Kwissa, M.; Amara, R. R.; Robinson, H. L.; Pulendran, B.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Kwissa, M.; Amara, R. R.; Robinson, H. L.; Pulendran, B.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Moss, B.] NIAID, Viral Dis Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PY 2008 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 480QF UT WOS:000268750600011 ER PT J AU von Briesen, H Fenyo, EM Holmes, H Karamov, EV Meyerhans, A Morgado, M AF von Briesen, H. Fenyo, E. M. Holmes, H. Karamov, E. V. Meyerhans, A. Morgado, M. TI Global HIV Vaccine Research Cryorepository - GHRC SO VACCINE LA English DT Meeting Abstract CT 2nd Vaccine Congress CY DEC 07-09, 2008 CL Boston, MA DE HIV-1 Cryobank; Cryorepository; CAVD; Technology platform C1 [Fenyo, E. M.] Lund Univ, S-22100 Lund, Sweden. [Holmes, H.] NIBSC, Potters Bar, Herts, England. [Meyerhans, A.] Univ Saarland, Saarbrucken, Germany. WHO, Geneva, Switzerland. Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa. NIH, Bethesda, MD 20892 USA. Siriraj Hosp, Bangkok, Thailand. RI Meyerhans, Andreas/D-3382-2014 OI Meyerhans, Andreas/0000-0003-0620-5317 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PY 2008 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 480QF UT WOS:000268750600205 ER PT J AU Parra, GI Vidales, G Gomez, JA Fernandez, FM Parreno, V Bok, K AF Parra, Gabriel I. Vidales, Graciela Gomez, Jorge A. Fernandez, Fernando M. Parreno, Viviana Bok, Karin TI Phylogenetic analysis of porcine rotavirus in Argentina: Increasing diversity of G4 strains and evidence of interspecies transmission SO VETERINARY MICROBIOLOGY LA English DT Article DE porcine rotavirus; genetic diversity; G genotype; Argentina ID POLYMERASE CHAIN-REACTION; GROUP-A ROTAVIRUSES; CAPSID PROTEIN VP7; MOLECULAR CHARACTERIZATION; SWINE ROTAVIRUSES; SEQUENCE-ANALYSIS; P-GENOTYPE; IDENTIFICATION; BOVINE; GENES AB Group A rotaviruses are one of the most frequently detected viral agents associated with neonatal diarrhea in piglets. In order to characterize rotavirus (RV) strains circulating in Argentinean swine, four porcine production farms located in Buenos Aires were studied. RV strains genotyped as P[6]G4, P[6]G8 and P[1]G6 were found in piglets under 30 days of age, without diarrhea. Phylogenetic and sequence analysis of the VP7 gene from G4 strains available in databases, reveals five porcine new lineages (III-VII) and three sublineages (VIIa-VIIc). The G4 porcine Argentinean strains were grouped with a porcine RV strain isolated in Brazil and another RV strain isolated from a child with diarrhea in Mexico, constituting an American lineage (VII). On the other hand, porcine G6 and G8 were closely related to RV's circulating in Argentinean cattle and South-American camelids, respectively. The fact that G4 porcine lineages were epidemiologically related to human strains, and G6 and G8 Argentinean porcine strains were found related to bovine and South-American camelids, respectively, suggests that pigs might play a crucial role as reservoir and generator of newly adapted emerging RV strains for human and other species. (C) 2007 Elsevier B.V. All rights reserved. C1 [Parra, Gabriel I.] Natl Univ Asuncion, IICS, Dept Biol Mol, Asuncion, Paraguay. [Vidales, Graciela] Natl Univ Lujan, Buenos Aires, DF, Argentina. [Gomez, Jorge A.; Bok, Karin] ANLIS, Natl Inst Infect Dis, Viral Gastroenteritis Lab, Buenos Aires, DF, Argentina. [Fernandez, Fernando M.; Parreno, Viviana] INTA, Natl Inst Agr Technol, Inst Virol, CICV y A, Buenos Aires, DF, Argentina. RP Bok, K (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike,Bldg 50,Room 6316, Bethesda, MD 20892 USA. EM bokk@niaid.nih.gov OI Parra, Gabriel/0000-0002-1102-4740 NR 37 TC 44 Z9 45 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 EI 1873-2542 J9 VET MICROBIOL JI Vet. Microbiol. PD JAN 1 PY 2008 VL 126 IS 1-3 BP 243 EP 250 DI 10.1016/j.vetmic.2007.06.06 PG 8 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 245HC UT WOS:000251924700026 PM 17659850 ER PT S AU Taub, DD AF Taub, Dennis D. BE Litwack, G TI Novel connections between the neuroendocrine and immune systems: The ghrelin immunoregulatory network SO VITAMINS AND HORMONES, GHRELIN SE Vitamins and Hormones LA English DT Review; Book Chapter ID GROWTH-HORMONE SECRETAGOGUE; T-CELL DEVELOPMENT; ADIPOSE-TISSUE; FOOD-INTAKE; ENDOTHELIAL-CELLS; RECEPTOR FAMILY; WEIGHT-LOSS; LEPTIN; OBESITY; RATS AB There appears to be bidirectional communication between the neuroendocrine and immune systems. This communication is mediated by way of an array of cytokines, hormones, and neuropeptides. Inflammatory cytokines released by immune cells have been shown to act on the central nervous system to control food intake and energy homeostasis. Decrease in food intake or anorexia is one of the most common symptoms of illness, injury, or inflammation. The adipocyte-derived hormone, leptin, is considered a critical sensory anorexigenic mediator that signals to the brain changes in stored energy, determined by an altered balance between food intake and energy expenditure and has been shown to exert certain proinflammatory effects on immune cells. In contrast, ghrelin, the endogenous ligand for growth hormone secretagogue receptors (GHSRs), is produced primarily from stomach serving as a potent circulating orexigen controlling energy expenditure, adiposity, and GH secretion. However, the functional role of ghrelin and GHS in immune cell function remains unclear. Here, we review the current literature supporting a role for ghrelin in controlling inflammation and immunity and the potential therapeutic use of ghrelin and GHSR agonists in the management of inflammation and in restoration of thymic function in im munocom promised individuals. (C) 2008 Elsevier Inc. C1 NIH, NIA, Immunol Lab, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), NIH, NIA, Immunol Lab, Baltimore, MD 21224 USA. FU Intramural NIH HHS NR 70 TC 27 Z9 32 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 978-0-12-373685-7 J9 VITAM HORM JI Vitam. Horm. PY 2008 VL 77 BP 325 EP + DI 10.1016/S0083-6729(06)77014-5 PG 24 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BGX34 UT WOS:000251127500014 PM 17983863 ER PT J AU Muniz, M Sheldon, S Schuller, RM Young, NS Klein, HG Leitman, SF Stroncek, DF AF Muniz, M. Sheldon, S. Schuller, R. M. Young, N. S. Klein, H. G. Leitman, S. F. Stroncek, D. F. TI Patient-specific transfusion-related acute lung injury SO VOX SANGUINIS LA English DT Article DE neutrophil antibodies; platelet; platelet transfusions; transfusion reactions; transfusion-related acute lung injury ID ANTIBODIES; PLASMA; TRALI; LEUKOPENIA; MODEL; BACK; 5B AB Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-associated mortality. The inadvertent transfusion of neutrophil antibodies can cause pulmonary transfusion reactions and TRALI. However, not all patients transfused with neutrophil antibodies experience transfusion reactions. A 22-year-old man with severe aplastic anaemia (SAA) experienced TRALI after a platelet transfusion. The donor was found to be alloimmunized to human neutrophil antigen (HNA)-3a, an antigen expressed by neutrophils from approximately 90% of Caucasians. Eleven other platelet components from this donor were transfused prior to this event and two caused reactions: one chills and one TRALI. Both episodes of TRALI occurred in the same male patient with SAA. The fact that one patient experienced TRALI following both exposures to anti-HNA-3a from the same donor whereas nine other recipients did not adds evidence to the observation that patient factors make a significant contribution to neutrophil antibody-mediated transfusion reactions. C1 [Muniz, M.; Sheldon, S.; Klein, H. G.; Leitman, S. F.; Stroncek, D. F.] NHLBI, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Young, N. S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Schuller, R. M.] Amer Red Cross, N Cent Blood Serv, St Paul, MN USA. RP Stroncek, DF (reprint author), NHLBI, Dept Transfus Med, Ctr Clin, NIH, 10 Ctr Dr MSC-1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov NR 14 TC 23 Z9 25 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JAN PY 2008 VL 94 IS 1 BP 70 EP 73 DI 10.1111/j.1423-0410.2007.00982.x PG 4 WC Hematology SC Hematology GA 241VO UT WOS:000251684100009 PM 18171330 ER PT J AU Reesink, HW Engelfriet, CP Hyland, CA Coghlan, P Tait, B Wsolak, M Keller, AJ Henn, G Mayr, WR Thomas, I Osselaer, JC Lambermont, M Beaten, M Wendel, S Qiu, Y Georgsen, J Krusius, T Maki, T Andreu, G Morel, P Lefrere, JJ Rebulla, P Giovanelli, S Butti, B Lecchi, L Mozzi, F van Hilten, JA Zwaginga, JJ Flanagan, P Flesland, O Brojer, E Letowska, M Akerblom, O Norda, R Prowse, C Dow, B Jarvis, L Davidson, F Kleinman, S Bianco, C Stramer, SL Dodd, RY Busch, MP AF Reesink, H. W. Engelfriet, C. P. Hyland, C. A. Coghlan, P. Tait, B. Wsolak, M. Keller, A. J. Henn, G. Mayr, W. R. Thomas, I. Osselaer, J. -C. Lambermont, M. Beaten, M. Wendel, S. Qiu, Y. Georgsen, J. Krusius, T. Maki, T. Andreu, G. Morel, P. Lefrere, J. -J. Rebulla, P. Giovanelli, S. Butti, B. Lecchi, L. Mozzi, F. van Hilten, J. A. Zwaginga, J. J. Flanagan, P. Flesland, O. Brojer, E. Letowska, M. Akerblom, O. Norda, R. Prowse, C. Dow, B. Jarvis, L. Davidson, F. Kleinman, S. Bianco, C. Stramer, S. L. Dodd, R. Y. Busch, M. P. TI Biobanks of blood from donors and recipients of blood products SO VOX SANGUINIS LA English DT Article ID HEPATITIS-C VIRUS; ALANINE AMINOTRANSFERASE LEVELS; HUMAN-IMMUNODEFICIENCY-VIRUS; C/HEPATITIS-G VIRUS; LIVER-DISEASE; TRANSFUSION; INFECTION; TRANSMISSION; FREQUENCY; COMPONENTS C1 [Reesink, H. W.] Sanquin Consulting Serv, NL-1600 AC Amsterdam, Netherlands. [Reesink, H. W.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands. [Engelfriet, C. P.] Sanquin Res & Sanquin Diagnost Serv, NL-1600 AD Amsterdam, Netherlands. [Hyland, C. A.; Coghlan, P.; Tait, B.; Wsolak, M.; Keller, A. J.] Australian Red Cross Blood Serv, Brisbane, Qld 4000, Australia. [Henn, G.; Mayr, W. R.] Osterreich Rotes Kreuz, Blutspendezentrale, A-1040 Vienna, Austria. [Thomas, I.] Sci Inst Publ Hlth Virol, B-1050 Brussels, Belgium. [Osselaer, J. -C.] Clin Mon Godinne UCL, Ctr Transfus, B-5530 Yvoir, Belgium. [Lambermont, M.] ULB Hop Erasme, Ctr Transfu, B-1070 Brussels, Belgium. [Beaten, M.] Bloedtransfus, Dienst Het Bloed, Rode Kruis Vlaanderen, B-2650 Edegem, Belgium. [Wendel, S.] Hosp Sirio Libanes, Sao Paulo, Brazil. [Qiu, Y.] Beijing Red Cross Blood Ctr, Beijing 100088, Peoples R China. [Georgsen, J.] Odense Univ Hosp, Dept Clin Immunol, Funen Transfus Serv, DK-5000 Odense C, Denmark. [Krusius, T.; Maki, T.] Finnish Red Cross Blood Serv, Helsinki, Finland. [Andreu, G.] Inst Natl Transfus Sanguine, F-75739 Paris, France. [Morel, P.] Estab Francais Sang Bourgogne Franche Comte, F-25000 Besancon, France. [Lefrere, J. -J.] Inst Natl Transfus Sanguine, F-75739 Paris, France. [Rebulla, P.; Giovanelli, S.; Butti, B.; Lecchi, L.] Ctr Med Trasfus Terapia Cellulare & Criobiol & Bi, Rome, Italy. [Mozzi, F.] Osped Maggiore, Policlin Mangiagalli & Regina Elena, Fdn IRCCS, Dept Regenerat Med,Ctr Transfus & Immunoematol, I-20122 Milan, Italy. [van Hilten, J. A.] Sanquin Blood Bank SW, NL-2333 BZ Leiden, Netherlands. [Zwaginga, J. J.] Sanquin Res, NL-1066 CX Amsterdam, Netherlands. [Zwaginga, J. J.] Leiden Univ, Med Ctr, Dept Immunol & Blood Transfus, NL-2300 RC Leiden, Netherlands. [Flanagan, P.] New Zealand Blood Serv, Auckland, New Zealand. [Flanagan, P.] Natl Off, Auckland, New Zealand. [Flesland, O.] Asker & Baerum Hosp, Lab Ctr, NO-1309 Rud, Norway. [Brojer, E.; Letowska, M.] Inst Haematol & Transfus Med, PL-02776 Warsaw, Poland. [Akerblom, O.; Norda, R.] Uppsala Univ, Akad Sjukhuset, Klin Immunol Transfus Med, S-75185 Uppsala, Sweden. [Prowse, C.; Dow, B.; Jarvis, L.; Davidson, F.] Scottish Natl Blood Transfus, Edinburgh EH17 7QT, Midlothian, Scotland. [Kleinman, S.] Univ British Columbia, NHLBI Repository Allocat Committee, Victoria, BC, Canada. [Kleinman, S.] NHCOI Repository Allocat Committee, Victoria, BC, Canada. [Bianco, C.] Amer Blood Ctr, Washington, DC 20005 USA. [Stramer, S. L.] Amer Red Cross, Sci Support Off, Gaithersburg, MD 20877 USA. [Dodd, R. Y.] Amer Red Cross, Jerome H Holland Lab Biomed Res, Rockville, MD 20855 USA. [Busch, M. P.] NHLBI Repository Allocat Comm, San Francisco, CA 94904 USA. [Busch, M. P.] Blood Syst Res Inst, Res & Sci Programs Blood Syst, San Francisco, CA 94904 USA. RP Reesink, HW (reprint author), Sanquin Consulting Serv, POB 9137, NL-1600 AC Amsterdam, Netherlands. EM h.reesink@sanquin.nl; p.engelfriet@sanquin.nl; chyland@arcbs.redcross.org.au; gabriela.henn@roteskreuz.at; isabelle.thomas@iph.fgov.be; snwendel@uninet.com.br; qiu444cn@yahoo.com.cn; georgsen@dadlnet.dk; tom.krusius@bts.redcross.fi; tiina.maki@bts.redcross.fi; gandreu@ints.fr; pascal.morel@efs.sante.fr; jjlefrere@ints.fr; prebulla@policlinico.mi.it; joost.vanhilten@sanquin.nl; j.zwaginga@sanquin.nl; peter.flanagan@nzblood.co.nz; oystein.flesland@sabhf.no; ebrojer@ihit.waw.pl; letowska@ihit.waw.pl; olof.akerblom@lul.se; rut.norda@akademiska.se; chris.prowse@snbts.csa.scot.nhs.uk; skleinman@shaw.ca; cbianco@americasblood.org; stramerS@usa.redcross.org; dodd@usa.redcross.org; mbusch@bloodsystems.org RI Rebulla, Paolo/I-7684-2015 OI Rebulla, Paolo/0000-0002-3875-5754 NR 47 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2008 VL 94 IS 3 BP 242 EP 260 DI 10.1111/j.1423-0410.2007.01020.x PG 19 WC Hematology SC Hematology GA 274DH UT WOS:000253981500012 PM 18225990 ER PT J AU Fadeyi, EA Adams, S Sheldon, S Leitman, SF Wesley, R Klein, HG Stroncek, DF AF Fadeyi, E. A. Adams, S. Sheldon, S. Leitman, S. F. Wesley, R. Klein, H. G. Stroncek, D. F. TI A preliminary comparison of the prevalence of transfusion reactions in recipients of platelet components from donors with and without human leucocyte antigen antibodies SO VOX SANGUINIS LA English DT Article DE HLA antibodies; neutrophil antibodies; platelets; transfusion reactions ID ACUTE LUNG INJURY; BLOOD-DONORS; PLASMA; BACK AB Background Human leucocyte antigen (HLA) antibodies have been implicated in transfusion-related acute lung injury, but the probability that the transfusion of a blood component containing HLA antibodies will cause a reaction is not known. This study compared the prevalence of reactions associated with the transfusion of platelet components with and without HLA antibodies. Study Design and Methods This retrospective study tested 96 consecutive apheresis platelet donors for HLA class I and II antibodies. Matched control donors without HLA antibodies were selected and records were reviewed to determine the proportion of components from each group that caused reactions. In addition, all apheresis platelet donors involved with two or more reactions were identified and tested for HLA class I antibodies. Results Five of the 96 donors had antibodies to class I or class II antigens and, of these, four had components transfused. The prevalence of reactions to components from these four donors with HLA antibodies and the 12 matched control donors without antibodies was similar (three reactions to 167 transfusions or 1.8% vs. three to 295 or 1.0%, respectively, P = 0.32). A retrospective review of the transfusion records from all platelet donors found that components from 22 caused two or more reactions and three (13.6%) had antibodies to HLA class I compared to 4.2% of the consecutively selected donors (P = 0.12). None of the patients experienced transfusion-related acute lung injury. Conclusion Reactions associated with transfusion of apheresis platelets containing HLA antibodies are unusual. C1 [Fadeyi, E. A.; Adams, S.; Sheldon, S.; Leitman, S. F.; Wesley, R.; Klein, H. G.; Stroncek, D. F.] NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Room 3C720,10 Ctr Dr MSC-1184, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov FU Intramural NIH HHS [Z01 CL002095-11] NR 13 TC 12 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2008 VL 94 IS 4 BP 324 EP 328 DI 10.1111/j.1423-0410.2008.01041.x PG 5 WC Hematology SC Hematology GA 288PN UT WOS:000254998400008 PM 18282262 ER PT B AU Emanuel, EJ Fuchs, VR AF Emanuel, Ezekiel J. Fuchs, Victor R. BE Furman, J TI A Comprehensive Cure The Guaranteed Health Care Access Plan-A Voucher-Style Reform SO WHO HAS THE CURE?: HAMILTON PROJECT IDEAS ON HEALTH CARE LA English DT Article; Book Chapter ID CONSUMER-CHOICE; PROMOTE QUALITY; UNITED-STATES; INSURANCE; PROPOSAL; COVERAGE; ECONOMY; 1990S C1 [Emanuel, Ezekiel J.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Emanuel, Ezekiel J.] Johns Hopkins Med Sch, Baltimore, MD USA. [Emanuel, Ezekiel J.] Stanford Med Sch, Stanford, CA USA. [Fuchs, Victor R.] Stanford Univ, Stanford, CA 94305 USA. RP Emanuel, EJ (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 23 TC 0 Z9 0 U1 0 U2 1 PU BROOKINGS INST PI WASHINGTON PA 1775 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA BN 978-0-8157-0199-6; 978-0-8157-3008-8 PY 2008 BP 91 EP 119 PG 29 WC Health Policy & Services; Political Science SC Health Care Sciences & Services; Government & Law GA BIC87 UT WOS:000327429500004 ER PT J AU Soyka, M Kranzler, HR Berglund, M Gorelick, D Hesselbrock, V Johnson, BA Moller, HJ AF Soyka, Michael Kranzler, Henry R. Berglund, Mats Gorelick, David Hesselbrock, Victor Johnson, Bankole A. Moeller, Hans-Juergen CA WFSBP Task Force TI World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of substance use and related disorders, Part 1: Alcoholism SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Review DE Alcoholism; pharmacotherapy; acamprosate; naltrexone; topiramate; carbamazepine; disulfiram; ondansetron; benzodiazepine ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; COGNITIVE-BEHAVIORAL THERAPY; DRUG-USE DISORDERS; TESTING COMBINED PHARMACOTHERAPIES; NATIONAL EPIDEMIOLOGIC SURVEY; CONTROLLED CLINICAL-TRIAL; PITUITARY BETA-ENDORPHIN; BLIND CONTROLLED TRIAL; RELAPSE PREVENTION AB These practice guidelines for the biological treatment of substance use disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal during the development of these guidelines was to review systematically all available evidence pertaining to the treatment of substance use disorders, and to reach a consensus on a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by physicians evaluating and treating people with substance use disorders and are primarily concerned with the biological treatment of adults suffering from substance use disorders. The data used to develop these guidelines were extracted primarily from various national treatment guidelines for substance use disorders, as well as from meta-analyses, reviews and randomized clinical trials on the efficacy of pharmacological and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorized into four levels of evidence (A-D). This first part of the guidelines covers the treatment of alcohol dependence; Part 2 will be devoted to the treatment of drug dependence. C1 [Soyka, Michael] Psychiat Hosp Meiringen, Meiringen, Switzerland. [Kranzler, Henry R.; Hesselbrock, Victor] Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT USA. [Berglund, Mats] Univ Hosp MAS, Dept Clin Alcohol Res, Malmo, Sweden. [Gorelick, David] Natl Inst Drug Abuse, Baltimore, MD USA. [Johnson, Bankole A.] Univ Virginia, Dept Psychiat Med, Charlottesville, VA USA. [Moeller, Hans-Juergen] Univ Munich, Dept Psychiat, Munich, Germany. RP Soyka, M (reprint author), Psychiat Hosp Meiringen, Meiringen, Switzerland. RI Wittchen, Hans-Ulrich/A-8507-2014 FU Medical Research Council [G0400575] NR 204 TC 45 Z9 45 U1 8 U2 17 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1562-2975 J9 WORLD J BIOL PSYCHIA JI World J. Biol. Psychiatry PY 2008 VL 9 IS 1 BP 6 EP 23 DI 10.1080/15622970801896390 PG 18 WC Psychiatry SC Psychiatry GA 262BD UT WOS:000253123100002 PM 18273737 ER PT J AU Bhatia, P Kolinski, M Moaddel, R Jozwiak, K Wainer, IW AF Bhatia, P. Kolinski, M. Moaddel, R. Jozwiak, K. Wainer, I. W. TI Determination and modelling of stereoselective interactions of ligands with drug transporters: A key dimension in the understanding of drug disposition SO XENOBIOTICA LA English DT Article DE P-glycoprotein; organic cation transporter; cellular membrane affinity chromatography; quantitative structure-activity relationship (QSAR); pharmacophore modelling; enantioselectivity; chirality ID CHROMATOGRAPHIC STATIONARY-PHASE; ORGANIC CATION TRANSPORTER; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; NONCOMPETITIVE INHIBITORS; ENANTIOSELECTIVE BINDING; AFFINITY-CHROMATOGRAPHY; MOLECULAR DOCKING; CELL-LINE; RECEPTOR AB 1. Stereochemistry is an important dimension in pharmacology and plays a role in every aspect of the pharmacological fate of chiral xenobiotics. This includes small molecule-drug transporter binding. 2. This paper reviews the reported stereoselectivities of substrate and inhibitor interactions with P-glycoprotein and the organic cation transporter obtained using standard functional and binding studies, as well as data obtained from online cellular membrane affinity chromatography studies. 3. The use of stereochemical data in quantitative structure-activity relationship (QSAR) and pharmacophore modelling is also addressed as is the effect of ignoring the fact that small molecule-drug transporter interactions take place in three-dimensional and asymmetric space. C1 [Bhatia, P.; Moaddel, R.; Wainer, I. W.] NIA, Natl Inst Hlth, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Kolinski, M.] Int Inst Mol & Cell Biol, Warsaw, Poland. [Jozwiak, K.] Med Univ Lublin, Lublin, Poland. RP Wainer, IW (reprint author), NIA, Natl Inst Hlth, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Wainerir@grc.nia.nih.gov FU Intramural NIH HHS [ZIA AG000297-13, Z99 AG999999] NR 45 TC 8 Z9 8 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PY 2008 VL 38 IS 7-8 BP 656 EP 675 DI 10.1080/00498250802109207 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 332JP UT WOS:000258079600003 PM 18668426 ER PT J AU Srimaroeng, C Perry, JL Pritchard, JB AF Srimaroeng, C. Perry, J. L. Pritchard, J. B. TI Physiology, structure, and regulation of the cloned organic anion transporters SO XENOBIOTICA LA English DT Review DE organic ion transporters; drug transporters; cloning; transport mechanisms; tissue distribution; SLC22A family; expression levels; structure-function ID SINGLE-NUCLEOTIDE POLYMORPHISMS; BLOOD-BRAIN-BARRIER; PROTEIN-KINASE-C; BASOLATERAL MEMBRANE-VESICLES; RENAL PROXIMAL TUBULES; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SHORT-TERM REGULATION; P-AMINOHIPPURIC ACID; MOLECULAR-CLONING; SUBSTRATE-SPECIFICITY AB 1. The transport of negatively charged drugs, xenobiotics, and metabolites by epithelial tissues, particularly the kidney, plays critical roles in controlling their distribution, concentration, and retention in the body. Thus, organic anion transporters (OATs) impact both their therapeutic efficacy and potential toxicity. 2. This review summarizes current knowledge of the properties and functional roles of the cloned OATs, the relationships between transporter structure and function, and those factors that determine the efficacy of transport. Such factors include plasma protein binding of substrates, genetic polymorphisms among the transporters, and regulation of transporter expression. 3. Clearly, much progress has been made in the decade since the first OAT was cloned. However, unresolved questions remain. Several of these issues - drug-drug interactions, functional characterization of newly cloned OATs, tissue differences in expression and function, and details of the nature and consequences of transporter regulation at genomic and intracellular sites - are discussed in the concluding Perspectives section. C1 [Srimaroeng, C.; Perry, J. L.; Pritchard, J. B.] NIEHS, Pharmacol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Pritchard, JB (reprint author), NIEHS, Pharmacol Lab, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM pritcha3@niehs.nih.gov OI Srimaroeng, Chutima/0000-0002-5537-1023 FU Intramural NIH HHS [Z01 ES080031-31] NR 214 TC 67 Z9 67 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PY 2008 VL 38 IS 7-8 BP 889 EP 935 DI 10.1080/00498250801927435 PG 47 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 332JP UT WOS:000258079600011 PM 18668434 ER PT J AU Funada, M Aoo, N Akitake, Y Kikura-Hanajiri, R Goda, Y Wada, K AF Funada, Masahiko Aoo, Naoya Akitake, Yoshiharu Kikura-Hanajiri, Ruri Goda, Yukihiro Wada, Kiyoshi TI Involvement of dopamine system on behavioral and pharmacological properties of p-fluoroamphetamine SO YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN LA Japanese DT Article DE dopamine; p-fluoroamphetamine; place conditioning; reward ID AMPHETAMINE AB The aim of the present study was to investigate the behavioral and neurochemical proper-ties of the amphetamine analogue p-fluoroamphetamine in mice. Administration of p-fluoroamphetamine produced marked hyperlocomotion. In a place conditioning study, p-fluoroamphetamine produced a significant conditioned place preference. The stimulus and rewarding effects of p-fluoroamphetamine were completely suppressed by dopamine D1 receptor antagonist SCH23390. In the drug discrimination substitution test, p-fluoroamphetamine fully substituted for the methamphetamine cue. p-Fluoroamphetamine also significantly increased the dopamine content in the limbic forebrain (containing the nucleus accumbens). Monoamine oxidase (MAO) activities in the limbic forebrain were suppressed by p-fluoroamphetamine, indicating that inhibitory effects of MAO may play an important role in the elevation of dopamine levels. Our findings demonstrated that the dopamine D1 receptors might be involved in the expression of p-fluoroamphetamine-induced hyperlocomotion and the rewarding effect. The present study also indicated that p-fluoroamphetamine resembles a psychostimulant, and may have a psychological dependence liability. C1 [Funada, Masahiko; Aoo, Naoya; Akitake, Yoshiharu; Wada, Kiyoshi] NCNP, NIMH, Dept Drug Dependence Res, Bethesda, MD 20892 USA. [Kikura-Hanajiri, Ruri; Goda, Yukihiro] NIHS, Div Pharmacognosy Phytochem & Narcot, Bethesda, MD 20892 USA. RP Funada, M (reprint author), NCNP, NIMH, Dept Drug Dependence Res, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 5 U2 5 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0031-6903 J9 YAKUGAKU ZASSHI JI Yakugaku Zasshi-J. Pharm. Soc. Jpn. PY 2008 VL 128 SU 3 BP 122 EP 125 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 348AD UT WOS:000259182300032 ER PT J AU Yang, JY Yang, MQ AF Yang, Jack Y. Yang, Mary Qu TI Predicting protein disorder by analyzing amino acid sequence SO BMC GENOMICS LA English DT Article AB Background: Many protein regions and some entire proteins have no definite tertiary structure, presenting instead as dynamic, disorder ensembles under different physiochemical circumstances. These proteins and regions are known as Intrinsically Unstructured Proteins (IUP). IUP have been associated with a wide range of protein functions, along with roles in diseases characterized by protein misfolding and aggregation. Results: Identifying IUP is important task in structural and functional genomics. We exact useful features from sequences and develop machine learning algorithms for the above task. We compare our IUP predictor with PONDRs (mainly neural-network-based predictors), disEMBL (also based on neural networks) and Globplot (based on disorder propensity). Conclusion: We find that augmenting features derived from physiochemical properties of amino acids (such as hydrophobicity, complexity etc.) and using ensemble method proved beneficial. The IUP predictor is a viable alternative software tool for identifying IUP protein regions and proteins. C1 [Yang, Jack Y.] Harvard Univ, Sch Med, Cambridge, MA 02115 USA. [Yang, Mary Qu] Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20852 USA. RP Yang, JY (reprint author), Harvard Univ, Sch Med, POB 400888, Cambridge, MA 02115 USA. EM jyang@bwh.Harvard.edu; yangma@mail.nih.gov NR 15 TC 5 Z9 6 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PY 2008 VL 9 SU 2 AR S8 DI 10.1186/1471-2164-9-S2-S8 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V92JQ UT WOS:000206244200009 PM 18831799 ER PT J AU Kumar, BM Yoo, JG Ock, SA Kim, JG Song, HJ Kan, EJ Cho, SK Lee, SL Cho, JH Balasubramanian, S Rho, GJ AF Kumar, Basavarajappa Mohana Yoo, Jae-Gyu Ock, Sun-A Kim, Jung-Gon Song, Hye-Jin Kan, Eun-Ju Cho, Seong-Keun Lee, Sung-Lim Cho, Jae-Hyeon Balasubramanian, Sivasankaran Rho, Gyu-Jin TI In vitro differentiation of mesenchymal progenitor cells derived from porcine umbilical cord blood SO MOLECULES AND CELLS LA English DT Article DE mesenchymal progenitor cells; in vitro differentiation; porcine; umbilical cord blood ID HUMAN BONE-MARROW; STEM-CELLS; STROMAL CELLS; MULTILINEAGE DIFFERENTIATION; NUCLEAR TRANSFER; ADIPOSE-TISSUE; EXPRESSION; BOVINE; SWINE AB Mesenchymal stem/progenitor cells (MPCs) were isolated from porcine umbilical cord blood (UCB) and their morphology, proliferation, cell cycle status, cell-surface antigen profile and expression of hematopoietic cytokines were characterized. Their capacity to differentiate in vitro into osteocytes, adipocytes and chondrocytes was also evaluated. Primary cultures of adherent porcine MPCs (pMPCs) exhibited a typical fibroblast-like morphology with significant renewal capacity and proliferative ability. Subsequent robust cell growth was indicated by the high percentage of quiescent (G0/G1) cells. The cells expressed the mesenchymal surface markers, CD29, CD49b and CD105, but not the hematopoietic markers, CD45 and CD133 and synthesized hematopoietic cytokines. Over 21 days of induction, the cells differentiated into osteocytes adipocytes and chondrocytes. The expression of lineage specific genes was gradually upregulated during osteogenesis, adipogenesis and chondrogenesis. We conclude that porcine umbilical cord blood contains a population of MPCs capable of self-renewal and of differentiating in vitro into three classical mesenchymal lineages. C1 [Kumar, Basavarajappa Mohana; Yoo, Jae-Gyu; Ock, Sun-A; Kim, Jung-Gon; Song, Hye-Jin; Kan, Eun-Ju; Lee, Sung-Lim; Cho, Jae-Hyeon; Balasubramanian, Sivasankaran; Rho, Gyu-Jin] Gyeongsang Natl Univ, Coll Vet Med, Jinju 660701, South Korea. [Cho, Seong-Keun] Gyeongsang Natl Univ, Div Appl Life Sci, Jinju 660701, South Korea. [Lee, Sung-Lim] NIA, NIH, Genet Lab, Dev Gen & Aging Sect, Baltimore, MD 21224 USA. [Balasubramanian, Sivasankaran] Tamil Nadu Vet & Anim Sci Univ, Madras Vet Coll, Dept Clin, Madras 600007, Tamil Nadu, India. RP Rho, GJ (reprint author), Gyeongsang Natl Univ, Coll Vet Med, Jinju 660701, South Korea. EM jinrho@gnu.ac.kr NR 33 TC 21 Z9 23 U1 0 U2 8 PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY PI SEOUL PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD DEC 31 PY 2007 VL 24 IS 3 BP 343 EP 350 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249RS UT WOS:000252248000006 PM 18182849 ER PT J AU Geissler, E Hecht, AM Horkay, F AF Geissler, Erik Hecht, Anne-Marie Horkay, Ferenc TI Scaling equations for a biopolymer in salt solution SO PHYSICAL REVIEW LETTERS LA English DT Article ID SEMIDILUTE POLYELECTROLYTE SOLUTIONS; LIGHT-SCATTERING; COUNTERION CONDENSATION; DNA CONDENSATION; MOLECULAR-WEIGHT; SELF-DIFFUSION; MOLAR-MASS; SMALL IONS; DEPENDENCE; DENSITY AB The effect of the simultaneous presence of monovalent and divalent cations on the thermodynamics of polyelectrolyte solutions is an incompletely solved problem. In physiological conditions, combinations of these ions affect structure formation in biopolymer systems. Dynamic light scattering measurements of the collective diffusion coefficient D and the osmotic compressibility of semidilute hyaluronan solutions containing different ratios of sodium and calcium ions are compared with simple polyelectrolyte models. Scaling relationships are proposed in terms of polymer concentration and ionic strength J of the added salt. Differences in the effects of sodium and calcium ions are found to be expressed only through J. C1 [Geissler, Erik; Hecht, Anne-Marie] Univ Grenoble 1, CNRS, Spectrometrie Phys Lab, UMR 5588, F-38402 St Martin Dheres, France. [Horkay, Ferenc] NICHD, Lab Integrat & Med Biophys, Sect Tissue Biophys & Biomimet, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Geissler, E (reprint author), Univ Grenoble 1, CNRS, Spectrometrie Phys Lab, UMR 5588, BP 87, F-38402 St Martin Dheres, France. FU Intramural NIH HHS NR 27 TC 5 Z9 5 U1 1 U2 13 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD DEC 31 PY 2007 VL 99 IS 26 AR 267801 DI 10.1103/PhysRevLett.99.267801 PG 4 WC Physics, Multidisciplinary SC Physics GA 246DE UT WOS:000251986900046 PM 18233606 ER PT J AU Konig, IR Malley, JD Weimar, C Diener, HC Ziegler, A AF Koenig, I. R. Malley, J. D. Weimar, C. Diener, H. -C. Ziegler, A. CA German Stroke Study Collaboration TI Practical experiences on the necessity of external validation SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Conference of the International-Society-for-Clinical-Biostatistics CY AUG 27-31, 2006 CL Geneva, SWITZERLAND SP Int Soc Clin Biostat DE prognosis; random forest; regression; stroke; support vector machine; validation ID LOGISTIC-REGRESSION MODELS; ACUTE ISCHEMIC-STROKE; PROGNOSTIC MODELS; PREDICTIVE MODELS; CLASSIFICATION; SURVIVAL AB The validity of prognostic models is an important prerequisite for their applicability in practical clinical settings. Here, we report on a specific prognostic study on stroke patients and describe how we explored the prediction performance of our model. We considered two practically highly relevant generalization aspects, namely, the model's performance in patients recruited at a later time point (temporal transportability) and in medical centers different from those used for model building (geographic transportability). To estimate the accuracy of the model, we investigated classical internal validation techniques and leave-one-center-out cross validation (CV). Prognostic models predicting functional independence of stroke patients were developed in a training set using logistic regression, support vector machines, and random forests (RFs). Tenfold CV and leave-one-center-out CV were employed to estimate temporal and geographic transportability of the models. For temporal and external validation, the resulting models were used to classify patients from a later time point and from different clinics. When applying the regression model or the RFs, accuracy in the temporal validation data was well predicted from classical internal validation. However, when predicting geographic transportability all approaches had difficulties. We observed that the leave-one-center-out CV yielded better estimates than classical CV. On the basis of our results, we conclude that external validation in patients from different clinics is required before a prognostic model can be applied in practice. Even validating the model in patients recruited merely at a later time point does not suffice to predict how it may fare with regard to another clinic. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Koenig, I. R.; Ziegler, A.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Malley, J. D.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. [Weimar, C.; Diener, H. -C.] Univ Duisburg Essen, Neurol Klin & Poliklin, Essen, Germany. RP Ziegler, A (reprint author), Med Univ Lubeck, Inst Med Biometrie & Stat, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM ziegler@imbs.uni-luebeck.de RI Konig, Inke/A-4544-2009; OI Ziegler, Andreas/0000-0002-8386-5397 NR 30 TC 39 Z9 40 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 30 PY 2007 VL 26 IS 30 BP 5499 EP 5511 DI 10.1002/sim.3069 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 254OJ UT WOS:000252595600013 PM 17907249 ER PT J AU Mattson, BJ Crombag, HS Mitchell, T Simmons, DE Kreuter, JD Morales, M Hope, BT AF Mattson, Brandi J. Crombag, Hans S. Mitchell, Tim Simmons, Danielle E. Kreuter, Justin D. Morales, Marisela Hope, Bruce T. TI Repeated amphetamine administration outside the home cage enhances drug-induced Fos expression in rat nucleus accumbens SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE sensitization; locomotor activity; stereotypy; striatum; environmental modulation; enkephalin; in situ hybridization ID MESSENGER-RNA EXPRESSION; EARLY GENE-EXPRESSION; COCAINE-SENSITIZED RATS; DOPAMINE-RECEPTOR GENE; VENTRAL TEGMENTAL AREA; C-FOS; STRIATAL NEURONS; ENVIRONMENTAL CONTEXT; BASAL GANGLIA; SUBTHALAMIC NUCLEUS AB Induction of the immediate early gene protein product Fos has been used extensively to assess neural activation in the striatum after repeated amphetamine administration to rats in their home cages. However, this technique has not been used to examine striatal activation after repeated administration outside the home cage, an environment where repeated drug administration produces more robust psychomotor sensitization. We determined the dose-response relationship for amphetamine-induced psychomotor activity and Fos expression in nucleus accumbens and caudate-putamen 1 week after repeated administration of amphetamine or saline in locomotor activity chambers. Repeated administration of amphetamine enhanced amphetamine-induced locomotor activity and stereotypy and Fos expression in nucleus accumbens, but not in caudate-putamen. In comparison, levels of Fos expression induced by 1 mg/kg amphetamine were not altered in nucleus accumbens or caudate-putamen by repeated amphetamine administration in the home cage. Double-labeling of Fos protein and enkephalin mRNA indicates that Fos is expressed in approximately equal numbers of enkephalin-negative and enkephalin-positive neurons in nucleus accumbens and caudate-putamen following injections outside the home cage. Furthermore, repeated amphetamine administration increased drug-induced Fos expression in enkephalin-positive, but not enkephalin-negative, neurons in nucleus accumbens. We conclude that repeated amphetamine administration outside the home cage recruits the activation of enkephalin-containing nucleus accumbens neurons during sensitized amphetamine-induced psychomotor activity. Published by Elsevier B.V. C1 NIDA, NIH, Dept Hlth & Human Serv, Behav Neurosci Branch,Intramural Res Program, Baltimore, MD 21224 USA. RP Hope, BT (reprint author), NIDA, NIH, Dept Hlth & Human Serv, Behav Neurosci Branch,Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bhope@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 FU Intramural NIH HHS [Z01 DA000467-04] NR 77 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD DEC 28 PY 2007 VL 185 IS 2 BP 88 EP 98 DI 10.1016/j.bbr.2007.07.024 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 237WI UT WOS:000251406700004 PM 17720257 ER PT J AU Kawasaki, BT Mistree, T Hurt, EM Kalathur, M Farrar, WL AF Kawasaki, Brian T. Mistree, Tashan Hurt, Elaine M. Kalathur, Madhuri Farrar, William L. TI Co-expression of the toleragenic glycoprotein, CD200, with markers for cancer stem cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE tumor immunity; cell surface molecules; tolerance; CD200; cancer stem cells ID ACUTE MYELOID-LEUKEMIA; PROSPECTIVE IDENTIFICATION; BREAST-CANCER; HAIR FOLLICLE; EXPRESSION; IMMUNITY; TISSUE; TUMORS AB Tumor immunology fundamentals suggest immunological surveillance has the ability to recognize malignant cells and kill them before a tumor develops. However, cancer cells employ evasion mechanisms whereby the immune system may be actively suppressed or even tolerized to the tumor. Recently cancer stem cells were linked to tumor initiation and formation. However, no reports have addressed whether these cells participate in a tumor's ability to evade immune surveillance. Recently the glycoprotein CD200, expressed within the innate immune system and other tissues and cells, was shown to be involved in tolerance. Here we describe CD200 co-expression with stem cell markers found on prostate, breast, brain, and colon cancers. This is the first report describing an immunomodulatory molecule on epithelial cancer stem cells. This important finding suggests a mechanism by which a tumor might evades immune system detection. Published by Elsevier Inc. C1 Ctr Canc Res, Natl Canc Inst, Natl Inst Hlth, Lab Canc Prevent, Frederick, MD 21702 USA. Ctr Canc Res, Canc Stem Cell Sect, Frederick, MD 21702 USA. RP Kawasaki, BT (reprint author), Ctr Canc Res, Natl Canc Inst, Natl Inst Hlth, Lab Canc Prevent, 1050 Boyles St, Bldg 560, Room 21-81, Frederick, MD 21702 USA. EM kawasakib@mail.nih.gov OI kalathur, madhuri/0000-0002-1534-5664 FU Intramural NIH HHS [NIH0011366921]; NCI NIH HHS [N01-CO-12400, N01CO12400]; PHS HHS [NIH0011366921] NR 26 TC 48 Z9 51 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 28 PY 2007 VL 364 IS 4 BP 778 EP 782 DI 10.1016/j.bbrc.2007.10.067 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 237FB UT WOS:000251358500011 PM 17964286 ER PT J AU Saroff, HA AF Saroff, Harry A. TI The model of Monod, Wyman, and Changeux generates two sets of parameters when applied to oxygen binding in hemoglobin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE mathematical model; hemoglobin; oxygen binding; fitting parameters AB The model of Monod, Wyman and Changeux is applied to binding phenomena where the Mass Law and its expansion are employed. In this communication the model of Monod, Wyman and Changeux (MWC) is applied to analyze the oxygen binding reaction in hemoglobin. The symmetrical structure of the MWC model with its three parameters is such that two sets of these parameters, rather than one, fit experimental data for the binding of oxygen to hemoglobin. Published by Elsevier Inc. C1 NIH, NIDDK, Biochim Genet Lab, Bethesda, MD 20892 USA. RP Saroff, HA (reprint author), NIH, NIDDK, Biochim Genet Lab, Bethesda, MD 20892 USA. EM saroff@helix.nih.gov FU Intramural NIH HHS [NIH0010042125]; PHS HHS [NIH0010042125] NR 6 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 28 PY 2007 VL 364 IS 4 BP 867 EP 869 DI 10.1016/j.bbrc.2007.10.078 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 237FB UT WOS:000251358500025 PM 17977512 ER PT J AU Zhu, A Huang, JB Clark, A Romero, R Petty, HR AF Zhu, Alping Huang, Ji-Biao Clark, Andrea Romero, Roberto Petty, Howard R. TI 2,5-deoxyfructosazine, a D-glucosamine derivative, inhibits T-cell interleukin-2 production better than D-glucosamine SO CARBOHYDRATE RESEARCH LA English DT Article DE immune cell; cytokine release; D-glucosamine; fructosazine ID POROUS GRAPHITIC CARBON; LINKED OLIGOSACCHARIDES; GLYCOPROTEINS; PYRAZINE; POLAR AB D-Glucosamine has been widely reported to have immuno suppressive actions on neutrophils, lymphocytes, and other cells of the immune system. However, under conditions used in biological experiments (e.g., neutral pH, and phosphate buffers), we have found that D-glucosamine self-reacts to form 2,5-deoxyfructosazine [2-(D-arabino-tetrahydroxybutyl)-5-(D-erythro-2,3,4-trihydroxybutyl)pyrazine] (1) and 2,5-fructosazine [2,5-biS(D-arabino-tetrahydroxybutyl)pyrazine] (2). When tested for bioactivity at nontoxic concentrations, these D-glucosamine derivatives were more effective inhibitors of IL-2 release from PHA-activated T cells than D-glucosamine. Hence, fructosazines constitute a novel class of immunomodulators. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Zhu, Alping; Huang, Ji-Biao; Clark, Andrea; Petty, Howard R.] Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. [Romero, Roberto] Hutzel Hosp, NICHHD, Perinatol Res Branch, Detroit, MI 48201 USA. [Petty, Howard R.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48105 USA. RP Petty, HR (reprint author), Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. EM hpetty@umich.edu FU Intramural NIH HHS; NIAID NIH HHS [R01 AI051789-05]; PHS HHS [51789] NR 15 TC 12 Z9 12 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD DEC 28 PY 2007 VL 342 IS 18 BP 2745 EP 2749 DI 10.1016/j.carres.2007.08.025 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 244NG UT WOS:000251872000006 PM 17892867 ER PT J AU Okada, T Ohzeki, JI Nakano, M Yoda, K Brinkley, WR Larionov, V Masumoto, H AF Okada, Teruaki Ohzeki, Jun-Ichirou Nakano, Megumi Yoda, Kinya Brinkley, William R. Larionov, Vladimir Masumoto, Hiroshi TI CENP-B controls centromere formation depending on the chromatin context SO CELL LA English DT Article ID ARTIFICIAL CHROMOSOME FORMATION; HISTONE H3 METHYLTRANSFERASE; ALPHA-SATELLITE ARRAY; DNA METHYLATION; NULL MICE; PROTEIN; COMPLEX; HETEROCHROMATIN; KINETOCHORE; IDENTIFICATION AB The centromere is a chromatin region that serves as the spindle attachment point and directs accurate inheritance of eukaryotic chromosomes during cell divisions. However, the mechanism by which the centromere assembles and stabilizes at a specific genomic region is not clear. The de novo formation of a human/mammalian artificial chromosome (HAC/MAC) with a functional centromere assembly requires the presence of alpha-satellite DNA containing binding motifs for the centromeric CENP-B protein. We demonstrate here that de novo centromere assembly on HAC/MAC is dependent on CENP-B. In contrast, centromere formation is suppressed in cells expressing CENP-B when alpha-satellite DNA was integrated into a chromosomal site. Remarkably, on those integration sites CENP-B enhances histone H3-K9 trimethylation and DNA methylation, thereby stimulating heterochromatin formation. Thus, we propose that CENP-B plays a dual role in centromere formation, ensuring de novo formation on DNA lacking a functional centromere but preventing the formation of excess centromeres on chromosomes. C1 [Okada, Teruaki; Masumoto, Hiroshi] Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan. [Ohzeki, Jun-Ichirou; Nakano, Megumi; Larionov, Vladimir; Masumoto, Hiroshi] NCI, Mol Pharmacol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Yoda, Kinya] Nagoya Univ, Biosci & Biotechnol Ctr, Chikusa Ku, Nagoya, Aichi 4648601, Japan. [Brinkley, William R.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Masumoto, H (reprint author), Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan. EM g44478a@nucc.cc.nagoya-u.ac.jp FU Intramural NIH HHS [, NIH0011582802]; PHS HHS [NIH0011582802] NR 45 TC 105 Z9 109 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 28 PY 2007 VL 131 IS 7 BP 1287 EP 1300 DI 10.1016/j.cell.2007.10.045 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249GV UT WOS:000252217200018 PM 18160038 ER PT J AU Di Padova, M Caretti, G Zhao, P Hoffman, EP Sartorelli, V AF Di Padova, Monica Caretti, Giuseppina Zhao, Po Hoffman, Eric P. Sartorelli, Vittorio TI MyoD acetylation influences temporal patterns of skeletal muscle gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYOCYTE ENHANCER FACTOR-2; MYOGENIC DIFFERENTIATION; TRANSCRIPTIONAL ACTIVATION; REGULATORY FACTORS; DISTINCT ROLES; DNA-BINDING; IN-VITRO; CHROMATIN; PROTEINS; COMPLEX AB MyoD is sufficient to initiate the skeletal muscle gene expression program. Transcription of certain MyoD target genes occurs in the early phases, whereas that of others is induced only at later stages, although MyoD is present throughout the differentiation process. MyoD acetylation regulates transcriptional competency, yet whether this post-translational modification is equally relevant for activation of all the MyoD targets is unknown. Moreover, the molecular mechanisms through which acetylation ensures that MyoD achieves its optimal activity remain unexplored. To address these two outstanding issues, we have coupled genome- wide expression profiling and chromatin immunoprecipitation in a model system in which MyoD or its nonacetylatable version was inducibly activated in mouse embryonic fibroblasts derived from MyoD(-/-) /Myf5 (-/-) mice. Our results reveal that MyoD acetylation influences transcription of selected genes expressed at defined stages of the muscle program by regulating chromatin access of MyoD, histone acetylation, and RNA polymerase II recruitment. C1 [Di Padova, Monica; Caretti, Giuseppina; Sartorelli, Vittorio] NIH, NIAMS, Lab Muscle Stem Cells & Gene Regulat, Bethesda, MD 20892 USA. [Zhao, Po; Hoffman, Eric P.] Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. RP Sartorelli, V (reprint author), NIH, NIAMS, Lab Muscle Stem Cells & Gene Regulat, 50 S Dr,Rm 1351, Bethesda, MD 20892 USA. EM sartorev@mail.nih.gov OI DI PADOVA, Monica/0000-0003-3808-7159 FU Intramural NIH HHS NR 44 TC 26 Z9 26 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2007 VL 282 IS 52 BP 37650 EP 37659 DI 10.1074/jbc.M707309200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243YQ UT WOS:000251833600041 PM 17965412 ER PT J AU Zhang, J Suzuki, K Hitomi, T Siragahan, RP AF Zhang, Juan Suzuki, Katsuhiro Hitomi, Tomohiro Siragahan, Reuben P. TI TOM1L1 is a Lyn substrate involved in Fc epsilon RI signaling in mast cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AFFINITY IGE RECEPTOR; PROTEIN-TYROSINE KINASE; BASOPHILIC LEUKEMIA-CELLS; ANTIGEN RECEPTOR; ADAPTER PROTEIN; CROSS-LINKING; VHS DOMAIN; SYK; ACTIVATION; PHOSPHORYLATION AB Protein- tyrosine kinase Lyn and Syk are critical for antigenreceptor-induced signal transduction in mast cells. To identify novel Lyn/Syk substrates, we screened an RBL-2H3 bacterial expression library for proteins that were tyrosine phosphorylated with baculoviral expressed Lyn or Syk. Five clones as potential Lyn substrates and eight clones as Syk substrates were identified including known substrates such as SLP-76, LAT, and alpha-tubulin. A potential substrate of Lyn identified was the molecule TOM1L1, which has several domains thought to be important for membrane trafficking and protein-protein interactions. Because the function of TOM1L1 is unclear, the rat TOM1L1 full-length cDNAwas isolated and used to express the protein in COS-1 and RBL-2H3 mast cells. In COS-1 cells, the co-transfection of TOM1L1 and Lyn, but not Syk, resulted in the tyrosine phosphorylation of TOM1L1. In RBL-2H3 mast cells, the overexpressed TOM1L1 was strongly tyrosine phosphorylated in non-stimulated cells, and this phosphorylation was enhanced by Fc epsilon RI aggregation. By subcellular fractionation, wild-type TOM1L1 was mainly in the cytoplasm with a small fraction constitutively associated with the membrane; this association was markedly reduced in deletion mutants lacking several of the protein interaction domains. The overexpression of TOM1L1 enhanced antigen-induced tumor necrosis factor (TNF) alpha generation and release. Both protein interaction domains (VHS and the coiled-coil domains) were required for the increased TNF alpha release, but not the increased TNF alpha generation. These results suggest that TOM1L1 is a novel protein involved in the Fc epsilon RI signal transduction for the generation of cytokines. C1 [Zhang, Juan; Suzuki, Katsuhiro; Hitomi, Tomohiro; Siragahan, Reuben P.] NIH, NIDCR, RAST Sect, Bethesda, MD 20892 USA. RP Siragahan, RP (reprint author), NIH, NIDCR, RAST Sect, OIIB,Bldg 10,Rm 1N106, Bethesda, MD 20892 USA. EM rs53x@nih.gov NR 40 TC 7 Z9 9 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2007 VL 282 IS 52 BP 37669 EP 37677 DI 10.1074/jbc.M705168200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243YQ UT WOS:000251833600043 PM 17977829 ER PT J AU Simonsen, L Viboud, C Taylor, RJ AF Simonsen, Lone Viboud, Cecile Taylor, Robert J. TI Effectiveness of influenza vaccination SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID MORTALITY C1 George Washington Univ, Sch Publ Hlth, Washington, DC 20037 USA. Fogarty Int Ctr, Bethesda, MD 20892 USA. SAGE Analytica, Bethesda, MD 20814 USA. RP Simonsen, L (reprint author), George Washington Univ, Sch Publ Hlth, Washington, DC 20037 USA. EM lone@gwu.edu OI Simonsen, Lone/0000-0003-1535-8526 NR 4 TC 9 Z9 12 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 27 PY 2007 VL 357 IS 26 BP 2729 EP 2730 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 245UO UT WOS:000251964500017 PM 18163274 ER PT J AU Garraux, G Peigneux, P Carson, RE Hallett, M AF Garraux, Gaetan Peigneux, Philippe Carson, Richard E. Hallett, Mark TI Task-related interaction between basal ganglia and cortical dopamine release SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; PET; C-11-raclopride; pallidum; SMA; motor skill learning ID TRANSCRANIAL MAGNETIC STIMULATION; SUPPLEMENTARY MOTOR AREA; MEDIAL PREFRONTAL CORTEX; PARKINSONS-DISEASE; CAUDATE-NUCLEUS; 6-HYDROXYDOPAMINE LESIONS; CEREBRAL-CORTEX; FRONTAL-CORTEX; STRIATUM; PET AB Dopamine (DA) is a powerful neuromodulator for a wide variety of behaviors. Considerable evidence accumulated from rodent and monkey experiments over the last two decades suggests that DA activity in the frontal cortex is reciprocally linked to that in functionally related basal ganglia (BG) structures. However, the functional importance of this in humans is still unknown. To address this issue, we measured endogenous DA release using positron emission tomography in 15 healthy subjects as they practiced the first training session of a finger sequence learning task. Significant results were observed not only in striatal areas but also in extrastriatal "motor" regions, bilaterally. Faster learning was specifically coupled to lower DA release in the sensorimotor part of the globus pallidus pars interna (GPi) contralateral to the moving hand, which was paralleled by a higher increase in DA levels in the pre-supplementary motor area (pre-SMA). This finding provides original evidence supporting a motor-learning-related interaction between DA release in left GPi and pre-SMA, a mechanism that may also apply to other anatomically and functionally interconnected BG and frontal cortical areas as a function of behavior. C1 [Garraux, Gaetan; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Carson, Richard E.] NIH, Ctr Clin, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. [Garraux, Gaetan; Peigneux, Philippe] Univ Liege, Cyclotron Res Ctr, B-4000 Liege, Belgium. [Garraux, Gaetan] Univ Liege, Dept Neurol, B-4000 Liege, Belgium. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,Ctr Dr 10,MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov RI Garraux, Gaetan/G-9050-2011; Carson, Richard/H-3250-2011; OI Carson, Richard/0000-0002-9338-7966; Peigneux, Philippe/0000-0003-4745-1434 FU Intramural NIH HHS NR 57 TC 28 Z9 28 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 26 PY 2007 VL 27 IS 52 BP 14434 EP 14441 DI 10.1523/JNEUROSCI.1595-07.2007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 245CB UT WOS:000251911100023 PM 18160651 ER PT J AU Laabs, TL Wang, H Katagiri, Y McCann, T Fawcett, JW Geller, HM AF Laabs, Tracy L. Wang, Hang Katagiri, Yasuhiro McCann, Thomas Fawcett, James W. Geller, Herbert M. TI Inhibiting glycosaminoglycan chain polymerization decreases the inhibitory activity of astrocyte-derived chondroitin sulfate proteoglycans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE axon guidance; granule neuron; siRNA; chondroitin polymerizing factor; Neu7 cells; matrix ID RAT SPINAL-CORD; CENTRAL-NERVOUS-SYSTEM; CREST CELL-MIGRATION; ADULT-RAT; AXON GROWTH; NEURITE OUTGROWTH; GLIAL SCAR; IN-VITRO; EXTRACELLULAR-MATRIX; REACTIVE ASTROCYTES AB Chondroitin sulfate proteoglycans (CSPGs) are upregulated in the CNS after injury and participate in the inhibition of axon regeneration mainly through their glycosaminoglycan (GAG) side chains. In the present study, we have identified a new way to alleviate the inhibition of axonal regeneration by CSPG GAGs. We have successfully decreased the amount of CSPG GAG produced by astrocytes by targeting chondroitin polymerizing factor (ChPF), a key enzyme in the CSPG biosynthetic pathway. Using short interfering RNA (siRNA), we reduced ChPF mRNA levels by 70% in both the Neu7 astrocyte cell line and primary rat astrocytes. This reduction leads to a decrease in ChPF protein levels and a reduced amount of CSPG GAG chains in the conditioned media (CM) of these cells. Secretion of neurocan by primary astrocytes and NG2 core protein by Neu7 cells transfected with ChPF siRNA is not decreased, suggesting that inhibiting GAG chain synthesis does not affect core protein trafficking from these cells. CM from siRNA-treated Neu7 cells is a less repulsive substrate for axons than CM from control cells. In addition, axonal outgrowth from cerebellar granule neurons is increased on or in CM from ChPF siRNA-treated Neu7 cells. These data indicate that targeting the biosynthesis of CSPG GAG is a potentially new therapeutic avenue for decreasing CSPG GAG produced by astrocytes after CNS injury. C1 [Laabs, Tracy L.; Wang, Hang; Katagiri, Yasuhiro; McCann, Thomas; Geller, Herbert M.] NHLBI, NIH, Dev Neurobiol Sect, Bethesda, MD 20892 USA. [Laabs, Tracy L.; Fawcett, James W.] Univ Cambridge, Ctr Brain Repair, Cambridge CB2 2PY, England. RP Geller, HM (reprint author), NHLBI, NIH, Dev Neurobiol Sect, 10 Ctr Dr,MSC 1754, Bethesda, MD 20892 USA. EM geller@helix.nih.gov OI Geller, Herbert/0000-0002-7048-6144; Fawcett, James/0000-0002-7990-4568 FU Intramural NIH HHS; Wellcome Trust [070467] NR 51 TC 73 Z9 77 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 26 PY 2007 VL 27 IS 52 BP 14494 EP 14501 DI 10.1523/JNEUROSCI.2807-07.2007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 245CB UT WOS:000251911100029 PM 18160657 ER PT J AU Reshetnyak, AV Armentano, MF Ponomarenko, NA Vizzuso, D Durova, OM Ziganshin, F Serebryakova, M Govorun, V Gololobov, G Morse, HC Friboulet, A Makker, SP Gabibov, AG Tramontano, A AF Reshetnyak, Andrey V. Armentano, Maria Francesca Ponomarenko, Natalia A. Vizzuso, Donnenica Durova, Oxana M. Ziganshin, Flustarn Serebryakova, Marina Govorun, Vadirn Gololobov, Gennady Morse, Herbert C., III Friboulet, Alain Makker, Sudesh P. Gabibov, Alexander G. Tramontano, Alfonso TI Routes to covalent catalysis by reactive selection for nascent protein nucleophiles SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID COMBINATORIAL ANTIBODY LIBRARIES; TRANSITION-STATE ANALOG; IN-VITRO SELECTION; PHAGE DISPLAY; IRREVERSIBLE INHIBITORS; MECHANISM; AFFINITY; ENZYMES; SERINE; SITE AB Reactivity-based selection strategies have been used to enrich combinatorial libraries for encoded biocatalysts having revised substrate specificity or altered catalytic activity. This approach can also assist in artificial evolution of enzyme catalysis from protein templates without bias for predefined catalytic sites. The prevalence of covalent intermediates in enzymatic mechanisms suggests the universal utility of the covalent complex as the basis for selection. Covalent selection by phosphonate ester exchange was applied to a phage display library of antibody variable fragments (scFv) to sample the scope and mechanism of chemical reactivity in a naive molecular library. Selected scFv segregated into structurally related covalent and noncovalent binders. Clones that reacted covalently' utilized tyrosine residues exclusively as the nucleophile. Two motifs were identified by structural analysis, recruiting distinct Tyr residues of the light chain. Most clones employed Tyr32 in CDR-L1, whereas a unique clone (A.17) reacted at Tyr36 in FR-L2. Enhanced phosphonylation kinetics and modest amidase activity of A.17 suggested a primitive catalytic site. Covalent selection may thus provide access to protein molecules that approximate an early apparatus for covalent catalysis. C1 [Armentano, Maria Francesca; Vizzuso, Donnenica; Makker, Sudesh P.] Univ Calif Davis, Sch Med, Davis, CA 95616 USA. [Reshetnyak, Andrey V.; Ponomarenko, Natalia A.; Durova, Oxana M.; Ziganshin, Flustarn; Gabibov, Alexander G.] Shemyakin & Ovchinikov Inst Bioorgan Chem RAS, Moscow 117871, Russia. [Reshetnyak, Andrey V.; Gabibov, Alexander G.] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119899, Russia. [Serebryakova, Marina; Govorun, Vadirn] Proteom Ctr Russian Acad Med Sci, Moscow, Russia. [Gololobov, Gennady] Univ Texas Houston, Sch Med, Houston, TX 77037 USA. [Morse, Herbert C., III] Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Immunopathol Lab, Rockville, MD 20852 USA. [Friboulet, Alain] Compiegne Technol Univ, CNRS UMR 6022, Compiegne, France. [Gabibov, Alexander G.] Russian Acad Sci, Inst Gene Biol, Moscow, Russia. RP Tramontano, A (reprint author), Univ Calif Davis, Sch Med, Davis, CA 95616 USA. EM tramontano@ucdavis.edu RI Serebryakova, Marina/E-2986-2012; OI Ponomarenko, Natalia/0000-0003-3129-3515; Morse, Herbert/0000-0002-9331-3705 FU Intramural NIH HHS; NCI NIH HHS [CA90564, R01 CA090564, R01 CA090564-01A2, R01 CA090564-02, R01 CA090564-03, R01 CA090564-04]; NIDDK NIH HHS [R01 DK033941-13S1, R21 DK070256-01A1] NR 33 TC 28 Z9 32 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 26 PY 2007 VL 129 IS 51 BP 16175 EP 16182 DI 10.1021/ja076528m PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 245YF UT WOS:000251974000071 PM 18044899 ER PT J AU Kanakry, CG Li, Z Nakai, Y Sei, Y Weinberger, DR AF Kanakry, Christopher G. Li, Zhen Nakai, Yoko Sei, Yoshitatsu Weinberger, Daniel R. TI Neuregulin-1 Regulates Cell Adhesion via an ErbB2/Phosphoinositide-3 Kinase/Akt-Dependent Pathway: Potential Implications for Schizophrenia and Cancer SO PLOS ONE LA English DT Article AB Background. Neuregulin-1 (NRG1) is a putative schizophrenia susceptibility gene involved extensively in central nervous system development as well as cancer invasion and metastasis. Using a B lymphoblast cell model, we previously demonstrated impairment in NRG1 alpha-mediated migration in cells derived from patients with schizophrenia as well as effects of risk alleles in NRG1 and catechol-O-methyltransferase (COMT), a second gene implicated both in schizophrenia susceptibility and in cancer. Methodology/Principal Findings. Here, we examine cell adhesion, an essential component process of cell motility, using an integrin-mediated cell adhesion assay based on an interaction between ICAM-1 and the CD11a/CD18 integrin heterodimer expressed on lymphoblasts. In our assay, NRG1 alpha induces lymphoblasts to assume varying levels of adhesion characterized by time-dependent fluctuations in the firmness of attachment. The maximum range of variation in adhesion over sixty minutes correlates strongly with NRG1a alpha-induced migration (r(2) = 0.61). NRG1 alpha-induced adhesion variation is blocked by erbB2, P13K, and Akt inhibitors, but not by PLC, ROCK, MLCK, or MEK inhibitors, implicating the erbB2/P13K/Akt1 signaling pathway in NRG1-stimulated, integrin-mediated cell adhesion. In cell lines from 20 patients with schizophrenia and 20 normal controls, cells from patients show a significant deficiency in the range of NRG1 alpha-induced adhesion (p = 0.0002). In contrast, the response of patient-derived cells to phorbol myristate acetate is unimpaired. The COMT Val108/158Met genotype demonstrates a strong trend towards predicting the range of the NRG1 alpha-induced adhesion response with risk homozygotes having decreased variation in cell adhesion even in normal subjects (p = 0.063). Conclusion/Significance. Our findings suggest that a mechanism of the NRG1 genetic association with schizophrenia may involve the molecular biology of cell adhesion. C1 [Kanakry, Christopher G.; Li, Zhen; Nakai, Yoko; Sei, Yoshitatsu; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Kanakry, Christopher G.] NIH, Howard Hughes Med Inst, Res Scholars Program, Chevy Chase, MD USA. RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov FU National Institute of Mental Health; NIH; The Howard Hughes Medical Institute FX The Intramural Research Program of the National Institute of Mental Health, NIH, provided the majority of the funding as well as the laboratory space in which these experiments were conducted. The Howard Hughes Medical Institute-NIH Research Scholars Program also provided funding that supported this research project. Neither sponsor was involved in the design or conducting of the research itself, the collection, analysis, or interpretation of data, or in the preparation or review of the resulting manuscript. NR 69 TC 40 Z9 40 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 26 PY 2007 VL 2 IS 12 AR e1369 DI 10.1371/journal.pone.0001369 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JG UT WOS:000207459700026 PM 18159252 ER PT J AU Kaneda, A Wang, CJ Cheong, R Timp, W Onyango, P Wen, B Lacobuzio-Donahuel, CA Ohlsson, R Andraos, R Pearson, MA Sharov, AA Longol, DL Ko, MSH Levchenko, A Feinberg, AP AF Kaneda, Atsushi Wang, Chiaochun J. Cheong, Raymond Timp, Winston Onyango, Patrick Wen, Bo Lacobuzio-Donahuel, Christine A. Ohlsson, Rolf Andraos, Rita Pearson, Mark A. Sharov, Alexei A. Longol, Dan L. Ko, Minoru S. H. Levchenko, Andre Feinberg, Andrew P. TI Enhanced sensitivity to IGF-II signalling links loss of imprinting of IGF2 to increased cell proliferation and tumour risk SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Akt; cancer; chemoprevention; epigenetics; signal transduction ID DNA-REPLICATION; GROWTH-FACTOR; H19 GENE; CANCER; MICE; PURIFICATION; ACTIVATION; EXPRESSION; INITIATION; RECEPTORS AB Loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2), leading to abnormal activation of the normally silent maternal allele, is a common human epigenetic population variant associated with a 5-fold increased frequency of colorectal neoplasia. Here, we show first that LOI leads specifically to increased expression of proliferation-related genes in mouse intestinal crypts. Surprisingly, LOI(+) mice also have enhanced sensitivity to IGF-II signaling, not simply increased IGF-II levels, because in vivo blockade with NVP-AEW541, a specific inhibitor of the IGF-II signaling receptor, showed reduction of proliferation-related gene expression to levels half that seen in LOI(-) mice. Signal transduction assays in microfluidic chips confirmed this enhanced sensitivity with marked augmentation of Akt/PKB signaling in LOI(+) cells at low doses of IGF-II, which was reduced in the presence of the inhibitor to levels below those found in LOI(-) cells, and was associated with increased expression of the IGF1 and insulin receptor genes. We exploited this increased IGF-II sensitivity to develop an in vivo chemopreventive strategy using the azoxymethane (AOM) mutagenesis model. LOI(+) mice treated with AOM showed a 60% increase in premalignant aberrant crypt foci (ACF) formation over LOI(-) mice. In vivo IGF-II blockade with NVP-AEW541 abrogated this effect, reducing ACF to a level 30% lower even than found in exposed LOI(-) mice. Thus, LOI increases cancer risk in a counterintuitive way, by increasing the sensitivity of the IGF-II signaling pathway itself, providing a previously undescribed epigenetic chemoprevention strategy in which cells with LOI are "IGF-II addicted" and undergo reduced tumorigenesis in the colon upon IGF-II pathway blockade. C1 [Kaneda, Atsushi; Timp, Winston; Onyango, Patrick; Wen, Bo; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Dept Med, Baltimore, MD 21205 USA. [Wang, Chiaochun J.; Cheong, Raymond; Timp, Winston; Levchenko, Andre] Johns Hopkins Univ, Sch Engn, Dept Biomed Engn, Baltimore, MD 21218 USA. [Lacobuzio-Donahuel, Christine A.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. [Ohlsson, Rolf] Uppsala Univ, Dept Genet & Dev, S-75236 Uppsala, Sweden. [Andraos, Rita; Pearson, Mark A.] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. [Sharov, Alexei A.; Longol, Dan L.; Ko, Minoru S. H.] NIA, Baltimore, MD 21224 USA. RP Levchenko, A (reprint author), Johns Hopkins Univ, Sch Med, Ctr Epigenet, Dept Med, 1064 Ross, 720 Rutland Ave, Baltimore, MD 21205 USA. EM afeinberg@jhu.edu; alev@jhu.edu RI Timp, Winston/B-5215-2008; Ko, Minoru/B-7969-2009 OI Timp, Winston/0000-0003-2083-6027; Ko, Minoru/0000-0002-3530-3015 FU Intramural NIH HHS; NCI NIH HHS [CA65145, R01 CA065145] NR 42 TC 64 Z9 67 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 26 PY 2007 VL 104 IS 52 BP 20926 EP 20931 DI 10.1073/pnas.0710359105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 247KJ UT WOS:000252077400056 PM 18087038 ER PT J AU Kovalevsky, AY Chumanevich, AA Liu, F Louis, JM Weber, IT AF Kovalevsky, Andrey Y. Chumanevich, Alexander A. Liu, Fengling Louis, John M. Weber, Irene T. TI Caught in the act: The 1.5 angstrom resolution crystal structures of the HIV-1 protease and the 154V mutant reveal a tetrahedral reaction lntermediate SO BIOCHEMISTRY LA English DT Article ID IMMUNODEFICIENCY VIRUS-1 PROTEASE; DRUG-RESISTANT MUTANTS; SUBSTRATE RECOGNITION; MOLECULAR-DYNAMICS; MECHANISM; COMPLEX; INHIBITOR; MUTATIONS; INSIGHTS; INTERMEDIATE AB HIV-1 protease (PR) is the target for several important antiviral drugs used in AIDS therapy. The drugs bind inside the active site cavity of PR where normally the viral polyprotein substrate is bound and hydrolyzed. We report two high-resolution crystal structures of wild-type PR (PRWT) and the multidrug-resistant variant with the 154V mutation (PR154V in complex with a peptide at 1.46 and 1.50 angstrom resolution, respectively. The peptide forms a gem-diol tetrahedral reaction intermediate (TI) in the crystal structures. Distinctive interactions are observed for the TI binding in the active site cavity of PRWT and PR154V. The mutant PR154V/Tl complex has lost water-mediated hydrogen bond interactions with the amides of Ile5O and Ile5O' in the flap. Hence, the structures provide insight into the mechanism of drug resistance arising from this mutation. The structures also illustrate an intermediate state in the hydrolysis reaction. One of the gern-diol hydroxide groups in the PRWT complex forms a very short (2.3 angstrom) hydrogen bond with the outer carboxylate oxygen of Asp25. Quantum chemical calculations based on this TI structure are consistent with protonation of the inner carboxylate oxygen of Asp25', in contrast to several theoretical studies. These TI complexes and quantum calculations are discussed in relation to the chemical mechanism of the peptide bond hydrolysis catalyzed by PR. C1 [Kovalevsky, Andrey Y.; Chumanevich, Alexander A.; Liu, Fengling; Weber, Irene T.] Georgia State Univ, Dept Biol, Mol Basis Dis Program, Atlanta, GA 30303 USA. [Louis, John M.] Georgia State Univ, Dept Chem, Mol Basis Dis Program, Atlanta, GA 30303 USA. [Weber, Irene T.] NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. RP Weber, IT (reprint author), Georgia State Univ, Dept Biol, Mol Basis Dis Program, Atlanta, GA 30303 USA. EM iweber@gsu.edu OI Kovalevsky, Andrey/0000-0003-4459-9142 FU Intramural NIH HHS [Z99 DK999999]; NIGMS NIH HHS [R01 GM062920-08, R01 GM062920-09, R01 GM062920-10, GM62920, U01 GM062920, R01 GM062920] NR 53 TC 33 Z9 36 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 25 PY 2007 VL 46 IS 51 BP 14854 EP 14864 DI 10.1021/bi700822g PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 242OG UT WOS:000251734500013 PM 18052235 ER PT J AU Krahn, JM Jackson, MR DeRose, EF Howell, EE London, RE AF Krahn, Joseph M. Jackson, Michael R. DeRose, Eugene F. Howell, Elizabeth E. London, Robert E. TI Crystal structure of a type II dihydrofolate reductase catalytic ternary complex SO BIOCHEMISTRY LA English DT Article ID SUBSTRATE-ASSISTED CATALYSIS; HYDRIDE TRANSFER STEP; ESCHERICHIA-COLI; TRANSITION-STATE; LIGAND-BINDING; ACTIVE-SITE; DISSOCIATION-CONSTANTS; PYRIDINE-NUCLEOTIDES; ENZYME CATALYSIS; R67 AB Type 11 dihydrofolate reductase (DHFR) is a plasmid-encoded enzyme that confers resistance to bacterial DHFR-targeted antifolate drugs. It forms a symmetric homotetramer with a central pore which functions as the active site. Its unusual structure, which results in a promiscuous binding surface that accommodates either the dihydrofolate (DHF) substrate or the NADPH cofactor, has constituted a significant limitation to efforts to understand its substrate specificity and reaction mechanism. We describe here the first structure of a ternary R67 DHFR center dot DHF center dot NADP(+) catalytic complex, resolved to 1.26 angstrom. This structure provides the first clear picture of how this enzyme, which lacks the active site carboxyl residue that is ubiquitous in Type I DHFRs, is able to function. In the catalytic complex, the polar backbone atoms of two symmetry-related 168 residues provide recognition motifs that interact with the carboxamide on the nicotinamide ring, and the N3-O4 amide function on the pteridine ring. This set of interactions orients the aromatic rings of substrate and cofactor in a relative endo geometry in which the reactive centers are held in close proximity. Additionally, a central, hydrogen-bonded network consisting of two pairs of Y69-Q67-Q67'-Y69' residues provides an unusually tight interface, which appears to serve as a "molecular clamp" holding the substrates in place in an orientation conducive to hydride transfer. In addition to providing the first clear insight regarding how this extremely unusual enzyme is able to function, the structure of the ternary complex provides general insights into how a mutationally challenged enzyme, i.e., an enzyme whose evolution is restricted to four-residues-at-a-time active site mutations, overcomes this fundamental limitation. C1 [Krahn, Joseph M.; DeRose, Eugene F.; London, Robert E.] Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Jackson, Michael R.; Howell, Elizabeth E.] Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN 37996 USA. RP London, RE (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov FU Intramural NIH HHS [Z01 ES050147-13, Z01 ES050111-19]; PHS HHS [HHSN273200700046U] NR 67 TC 20 Z9 21 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 25 PY 2007 VL 46 IS 51 BP 14878 EP 14888 DI 10.1021/bi701532r PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 242OG UT WOS:000251734500015 PM 18052202 ER PT J AU Song, C Wang, Q Li, CCH AF Song, Changcheng Wang, Qing Li, Chou-Chi H. TI Characterization of the aggregation-prevention activity of p97/valosin-containing protein SO BIOCHEMISTRY LA English DT Article ID VALOSIN-CONTAINING PROTEIN; TRANSCRIPTION FACTOR; ATPASE; PROTEASOME; CHAPERONE; UBIQUITIN; CDC48/P97; HOMOLOG; COMPLEX; P97-VCP AB The 97 kDa valosin-containing protein (VCP) belongs to a highly conserved AAA (ATPases associated with a variety of activities) family and contains two ATPase domains, D1 and D2. VCP participates in numerous cellular activities, such as membrane fusion, postmitotic Golgi reassembly, endoplasmic reticulum-associated degradation, ubiquitin-proteasome-mediated proteolysis, and many others. In performing these activities, VCP presumably acts as a molecular chaperone that prevents protein aggregation and modifies protein conformation. In this study, we characterized the aggregation-prevention activity of VCP and identified the structural requirement for this activity. We used multiple methods to treat aggregation-prone luciferase (Luc) and showed that VCP prevents the aggregation of Luc in vitro. These results are in agreement; in vivo RNA interference analyses showed that a reduction of VCP level results in more aggregation of Luc in cells. Structural and functional analyses further demonstrated that the D I domain of VCP is sufficient to mediate the aggregation-prevention activity, which does not require ATP binding, ATP hydrolysis, or a hexameric structure of VCP. Together, these results indicate that (1) VCP prevents protein aggregation in vitro and in vivo, (2) this aggregation-prevention activity is mediated mainly through the D I domain of VCP, and (3) this activity does not require ATPase activity or a hexameric structure of VCP. C1 [Song, Changcheng; Wang, Qing; Li, Chou-Chi H.] NCI, Lab Canc Prevent, Frederick, MD 21702 USA. [Song, Changcheng; Li, Chou-Chi H.] SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. RP Song, C (reprint author), NCI, Lab Canc Prevent, Frederick, MD 21702 USA. EM songc@nciferf.gov FU NCI NIH HHS [N01-CO-12400] NR 43 TC 24 Z9 24 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 25 PY 2007 VL 46 IS 51 BP 14889 EP 14898 DI 10.1021/bi700499j PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 242OG UT WOS:000251734500016 PM 18044963 ER PT J AU Wimalasena, DS Cramer, JC Janowiak, BE Juris, SJ Melnyk, RA Anderson, DE Kirk, KL Collier, RJ Bann, JG AF Wimalasena, D. Shyamali Cramer, John C. Janowiak, Blythe E. Juris, Stephen J. Melnyk, Roman A. Anderson, D. Eric Kirk, Kenneth L. Collier, R. John Bann, James G. TI Effect of 2-fluorohistidine labeling of the anthrax protective antigen on stability, pore formation, and translocation SO BIOCHEMISTRY LA English DT Article ID TOXIN RECEPTOR; CAPILLARY MORPHOGENESIS; DIAZONIUM SALTS; LETHAL FACTOR; PROTEIN; HISTIDINE; PHOTOCHEMISTRY; IDENTIFICATION; APOMYOGLOBIN; MUTATIONS AB The action of anthrax toxin relies in part upon the ability of the protective antigen (PA) moiety to form a heptameric pore in the endosomal membrane, providing a portal for entry of the enzymic moieties of the toxin into the cytosol. Pore formation is dependent on a conformational change in the heptameric prepore that occurs in the neutral to mildly acidic pH range, and it has been hypothesized that protonation of one or more histidine residues triggers this transition. To test this hypothesis, we used biosynthetic methods to incorporate the unnatural amino acid analogue 2-fluorohistidine (2-FHis) into PA. 2-FHis is isosteric with histidine but resists protonation at physiological pH values due to a dramatically reduced side-chain pK(a) (similar to 1). We found that 2-FHis-labeled PA was biologically inactive, as judged by its inability to deliver a model intracellular effector, LFN-DTA, to the cytosol of CHO-K1 cells. However, whereas 2-FHis blocked a conformational transition in the full-length PA(83) protein in the pH 5-6 range, the pH dependence of prepore-to-pore conversion of (PA(63))7 was unchanged from the wild-type protein, implying that this conversion is not dependent on His protonation. Consistent with this result, the labeled, trypsin-activated PA was able to permeabilize liposomes to K+ and retained pore-forming activity in planar phospholipid bilayers. The pores in planar bilayers were incapable, however, of translocating a model ligand in response to a transmembrane pH gradient or elevated voltage. The results indicate that protonation of residues other than His, presumably Glu and/or Asp side chains, triggers pore formation in vitro, but His residues are nonetheless important for PA functioning in vivo. C1 [Wimalasena, D. Shyamali; Bann, James G.] Wichita State Univ, Dept Chem, Wichita, KS 67260 USA. [Cramer, John C.; Kirk, Kenneth L.] NIDDK, NIH, Lab Bioorgan Chem, Bethesda, MD 20892 USA. [Anderson, D. Eric] NIDDK, NIH, Proteom & Mass Spectrom Facil, Bethesda, MD 20892 USA. [Juris, Stephen J.; Collier, R. John] Harvard Med Sch, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Bann, JG (reprint author), Wichita State Univ, Dept Chem, Wichita, KS 67260 USA. EM Jim.Bann@wichita.edu OI Collier, R John/0000-0002-2427-4239 FU Intramural NIH HHS; NIAID NIH HHS [AI22021, U54 AI057160] NR 41 TC 20 Z9 20 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 25 PY 2007 VL 46 IS 51 BP 14928 EP 14936 DI 10.1021/bi701763z PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 242OG UT WOS:000251734500020 PM 18044973 ER PT J AU Skoumbourdis, AP Moore, S Landsman, M Thomas, CJ AF Skoumbourdis, Amanda P. Moore, Susanna Landsman, Marc Thomas, Craig J. TI Synthesis of substituted 2-phenylhistamines via a microwave promoted Suzuki coupling SO TETRAHEDRON LETTERS LA English DT Article ID HISTAMINE H-1-RECEPTOR; RECEPTOR; ANALOGS; IDENTIFICATION; LIGANDS; AGONIST AB Substitutions on the 2-position of the imidazole ring of histamine have proven useful in a number of biochemical settings. Current art for the synthesis of these constructs relies upon a cumbersome and low-yielding condensation reaction. Here-in we report a new procedure for the synthesis of a series of substituted 2-phenylhistamines utilizing a microwave-promoted Suzuki coupling. Published by Elsevier Ltd. C1 [Skoumbourdis, Amanda P.; Moore, Susanna; Landsman, Marc; Thomas, Craig J.] NIH, NHGRI, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. RP Thomas, CJ (reprint author), NIH, NHGRI, NIH Chem Genom Ctr, NIH 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA. EM craigt@nhgri.nih.gov FU Intramural NIH HHS [Z99 HG999999] NR 14 TC 8 Z9 8 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD DEC 24 PY 2007 VL 48 IS 52 BP 9140 EP 9143 DI 10.1016/j.tetlet.2007.10.119 PG 4 WC Chemistry, Organic SC Chemistry GA 244DO UT WOS:000251846400018 PM 19112479 ER PT J AU Ahn, BH Park, MH Lee, YH Min, DS AF Ahn, Bong-Hyun Park, Mi Hee Lee, Young Han Min, Do Sik TI Phorbol myristate acetate-induced Egr-1 expression is suppressed by phospholipase D isozymes in human glioma cells SO FEBS LETTERS LA English DT Article DE glioma; phospholipse D; PMA; Egr-1; PI3K ID EARLY GROWTH RESPONSE-1; TRANSCRIPTION FACTOR; GENE EGR-1; APOPTOSIS; TRANSFORMATION; PROTEIN; CANCER; P53 AB Early growth response-1 (Egr-1) is involved in the regulation of cell growth. Here, we found that overexpression of phospholipase D (PLD) isozymes decreased tumor promoter phorbol myristate acetate (PMA)-induced Egr-1 expression and transactivation in glioma cells. Suppression of PMA-induced Egr-1 was dependent on the expression level of PLD isozymes. Overexpression of catalytically inactive PLD, treatment with PA, and prevention of PA dephosphorylation by 1-propranolol significantly suppressed PMA-induced Egr-1 expression. PLD-induced suppression of Egr-1 was reversed by inhibition of phosphatidylinositol 3-kinase (PI3K). Taken together, these results suggest that elevated expression and activity of PLD attenuate PMA-induced Egr-1 expression via PI3K pathway. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved. C1 [Park, Mi Hee; Min, Do Sik] Pusan Natl Univ, Coll Nat Sci, Dept Mol Biol, Pusan 609735, South Korea. [Ahn, Bong-Hyun; Min, Do Sik] NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. [Lee, Young Han] Konkuk Univ, IBST, Dept Biomed Sci & Technol, Seoul, South Korea. RP Min, DS (reprint author), Pusan Natl Univ, Coll Nat Sci, Dept Mol Biol, 30 Jangjeon Dong, Pusan 609735, South Korea. EM minds@pusan.ac.kr NR 16 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 22 PY 2007 VL 581 IS 30 BP 5940 EP 5944 DI 10.1016/j.febslet.2007.11.077 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 267CX UT WOS:000253488200034 PM 18067864 ER PT J AU Nallamsetty, S Waugh, DS AF Nallamsetty, Sreedevi Waugh, David S. TI Mutations that alter the equilibrium between open and closed conformations of Escherichia coli maltose-binding protein impede its ability to enhance the solubility of passenger proteins SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE maltose-bin ding protein; solubility enhancer; affinity tag; fusion protein; solubility tag ID FUSION PROTEINS; SOLUBLE-PROTEIN; IN-VITRO; AFFINITY; EXPRESSION; PARTNERS; TAGS AB Certain highly soluble proteins, such as Escherichia coli maltose-binding protein (MBP), have the ability to enhance the solubility of their fusion partners, making them attractive vehicles for the production of recombinant proteins, yet the mechanism of solubility enhancement remains poorly understood. Here, we report that the solubility-enhancing properties of MBP are dramatically affected by amino acid substitutions that alter the equilibrium between its "open" and "closed" conformations. Our findings indicate that the solubility-enhancing activity of MBP is mediated by its open conformation and point to a likely role for the ligand-binding cleft in the mechanism of solubility enhancement. Published by Elsevier Inc. C1 NCI, Canc Res Ctr, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Canc Res Ctr, Macromol Crystallog Lab, POB B, Frederick, MD 21702 USA. EM waughd@ncifcrf.gov FU Intramural NIH HHS [Z01 BC010341-07] NR 24 TC 16 Z9 18 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 21 PY 2007 VL 364 IS 3 BP 639 EP 644 DI 10.1016/j.bbrc.2007.10.060 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 232PB UT WOS:000251030500036 PM 17964542 ER PT J AU Kadyrov, FA Holmes, SF Arana, ME Lukianova, OA O'Donnell, M Kunkel, TA Modrich, P AF Kadyrov, Farid A. Holmes, Shannon F. Arana, Mercedes E. Lukianova, Olga A. O'Donnell, Mike Kunkel, Thomas A. Modrich, Paul TI Saccharomyces cerevisiae MutL alpha is a mismatch repair endonuclease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; MUTATOR PHENOTYPES; ATP BINDING; DNA-BINDING; YEAST; REPLICATION; SYSTEM; EXCISION; CLAMP; GENE AB MutL homologs are crucial for mismatch repair and genetic stability, but their function is not well understood. Human MutL alpha (MLH1-PMS2 heterodimer) harbors a latent endonuclease that is dependent on the integrity of a PMS2 DQHA(X)(2)E(X)(4)E motif (Kadyrov, F. A., Dzantiev, L., Constantin, N., and Modrich, P. (2006) Cell 126, 297-308). This sequence element is conserved in many MutL homologs, including the PMS1 subunit of Saccharomyces cerevisiae MutL alpha, but is absent in MutL proteins from bacteria like Escherichia coli that rely on d(GATC) methylation for strand directionality. We show that yeast MutL alpha is a strand-directed endonuclease that incises DNA in a reaction that depends on a mismatch, yMutS alpha, yRFC, yPCNA, ATP, and a pre-existing strand break, whereas E. coli MutL is not. Amino acid substitution within the PMS1 DQHA(X)(2)E(X)(4)E motif abolishes yMutL alpha endonuclease activity in vitro and confers strong genetic instability in vivo, but does not affect yMutL alpha ATPase activity or the ability of the protein to support assembly of the yMutL alpha center dot yMutS alpha center dot heteroduplex ternary complex. The loaded form of yPCNA may play an important effector role in directing yMutL alpha incision to the discontinuous strand of a nicked heteroduplex. C1 [Kadyrov, Farid A.; Lukianova, Olga A.; Modrich, Paul] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. [Modrich, Paul] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. [Holmes, Shannon F.; Arana, Mercedes E.; Kunkel, Thomas A.] Natl Inst Hlth, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Holmes, Shannon F.; Arana, Mercedes E.; Kunkel, Thomas A.] Natl Inst Hlth, Genet Mol Lab, NIEHS, Res Triangle Pk, NC 27709 USA. [O'Donnell, Mike] Rockefeller Univ, Lab DNA Replicat, New York, NY 10021 USA. [O'Donnell, Mike] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. RP Modrich, P (reprint author), Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. EM modrich@biochem.duke.edu OI O'Donnell, Michael/0000-0001-9002-4214 FU Howard Hughes Medical Institute; Intramural NIH HHS [Z01 ES065089-11]; NIGMS NIH HHS [GM 38839, GM45190, R01 GM038839, R01 GM045190, R01 GM045190-17, R37 GM038839] NR 42 TC 122 Z9 122 U1 0 U2 15 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 21 PY 2007 VL 282 IS 51 BP 37181 EP 37190 DI 10.1074/jbc.M707617200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241GX UT WOS:000251646000044 PM 17951253 ER PT J AU Yagi, H Jerina, DM AF Yagi, Haruhiko Jerina, Donald M. TI Fluorinated alcohol mediated displacement of the C-10 acetoxy group of benzo[a]pyrene-7,8,9,10-tetrahydrotetraol tetraacetates: A new route to diol epoxide - Deoxyguanosine adducts SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID 7,8-DIOL 9,10-EPOXIDE ADDUCTS; PALLADIUM-CATALYZED SYNTHESIS; SYNDROME HELICASE ACTIVITY; VACCINIA TOPOISOMERASE; DNA-POLYMERASE; EFFICIENT SYNTHESIS; NUCLEOSIDE ADDUCTS; CIS; DEOXYADENOSINE; TRANSESTERIFICATION AB We describe a novel trifluoroethanol (TFE) or hexafluoropropan-2-ol (HFP) mediated substitution reaction of the bay-region C-10 acetoxy group in four stereoisomeric 7,8,9, 10-tetraacetoxy-7,8,9, 10-tetrahydrobenzo[a]pyrenes (tetraol tetraacetates, two pairs of cis and trans isomers at the 9, 10 positions) by the exocyclic N-2-amino group of O-6-allyl-3',5'-di-O-(tert-butyidimethylsilyt)-2'-deoxyguanosine (3). The tetraacetates are derived from cis and trans hydrolysis of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P DE-1) and of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P DE-2) at C-10 followed by acetylation. Excellent yields and high regioselectivity were observed. Similar cis/trans product ratios were observed for each set of cis and trans tetraol tetraacetates derived from DE-1 (similar to 75/25) and from DE-2 (similar to 67/33) in HFP. This strongly suggests that the substitution proceeds via an S(N)1 mechanism involving a carbocation intermediate that is common to the cis and trans tetraacetates. Since it is likely that the cis and trans products from 3 arise from different conformations of the carbocation, its lifetime must be sufficiently long to permit conformational equilibration before its capture by the purine nucleophile. The corresponding reaction of (+/-)-9 alpha-bromo-7 beta,8 alpha,10 beta-triacetoxy-7,8,9,10-tetrahydrobenzo[a]pyrene with 3 in HFP was highly regio- and stereoselective and gave exclusively trans 10 beta-adducts. This newly developed substitution reaction provides an attractive alternative synthetic strategy for the preparation of polycyclic hydrocarbon adducted oligonucleotide building blocks. C1 [Yagi, Haruhiko; Jerina, Donald M.] NIDDK, Natl Inst Hlth, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Jerina, DM (reprint author), NIDDK, Natl Inst Hlth, Sect Oxidat Mechanisms, Bldg 8A,Room 1A01, Bethesda, MD 20892 USA. EM dmjerina@nih.gov NR 35 TC 3 Z9 3 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD DEC 21 PY 2007 VL 72 IS 26 BP 9983 EP 9990 DI 10.1021/jo701705c PG 8 WC Chemistry, Organic SC Chemistry GA 241JP UT WOS:000251653000015 PM 18047370 ER PT J AU Millum, J Emanuel, EJ AF Millum, Joseph Emanuel, Ezekiel J. TI Ethics - The ethics of international research with abandoned children SO SCIENCE LA English DT Editorial Material ID CLINICAL-RESEARCH; TRIALS; TRANSMISSION; CARE C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM eemanuel@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 14 TC 35 Z9 35 U1 3 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 21 PY 2007 VL 318 IS 5858 BP 1874 EP 1875 DI 10.1126/science.1153822 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 243HE UT WOS:000251786600041 PM 18096792 ER PT J AU Lathia, JD Patton, B Eckley, DM Magnus, T Mughal, MR Sasaki, T Caldwell, MA Rao, MS Mattson, MP Ffrench-Constant, C AF Lathia, Justin D. Patton, Bruce Eckley, D. Mark Magnus, Tim Mughal, Mohamed R. Sasaki, Takako Caldwell, Maeve A. Rao, Mahendra S. Mattson, Mark P. Ffrench-Constant, Charles TI Patterns of laminins and integrins in the embryonic ventricular zone of the CNS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE neural stem cell; stem cell niche; extracellular matrix; laminin; integrin; syndecan; dystroglycan; neurogenesis; radial glia ID NEURAL STEM-CELLS; HEPARAN-SULFATE PROTEOGLYCANS; CONGENITAL MUSCULAR-DYSTROPHY; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; ALPHA-4 CHAIN; CHROMOSOME CONDENSATION; MONOCLONAL-ANTIBODY; PROGENITOR CELLS; PLASMA-MEMBRANE AB The extracellular matrix (ECM) provides both a physical framework and a microenvironment that supplies instructive signals from the earliest stages of multicellular development. As a first step toward understanding the role of the ECM in regulating the behavior of neural stem cells (NSCs), here we show the localization of laminins, a heterotrimeric family of ECM molecules expressed in many different stem cell microenviromnents, and their corresponding receptors in the embryonic murine ventricular zone (VZ) within which the NSCs undergo symmetrical and asymmetrical divisions required for cortical development. In addition to the presence of laminins containing both the alpha 2 and alpha 4 chains, we find distinct patterns of ECM receptor expression in the VZ and in the overlying cortex. Neural stem cells derived from the VZ express high levels of the integrin laminin receptor alpha 6 beta 1. At developmental stages at which NSCs undergo asymmetrical divisions, integrin beta 1 was unevenly distributed in some mitotic pairs at the ventricular wall. These results suggest a significant role in the regulation of NSC fate for laminin/integrin signaling within the microenvironment of the VZ and provide a framework for future molecular and cellular analyses of the role of the ECM in neural development. C1 Univ Cambridge, Ctr Brain Repair, Dept Pathol, Cambridge CB2 1QP, England. Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97239 USA. NIA, Genet Lab, Baltimore, MD 21224 USA. Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. Invitrogen Corp, Corp Res Labs, Carlsbad, CA 92008 USA. Johns Hopkins Sch Med, Baltimore, MD 21287 USA. RP Ffrench-Constant, C (reprint author), Univ Cambridge, Ctr Brain Repair, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England. EM cfc@mole.bio.cam.ac.uk RI Mattson, Mark/F-6038-2012; Eckley, Mark/M-3526-2014 OI Eckley, Mark/0000-0003-2296-5164 FU Intramural NIH HHS; NINDS NIH HHS [NS40759]; Wellcome Trust NR 88 TC 72 Z9 74 U1 0 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 20 PY 2007 VL 505 IS 6 BP 630 EP 643 DI 10.1002/ene.21520 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 232AX UT WOS:000250991600002 PM 17948866 ER PT J AU Curco, D Nussinov, R Aleman, C AF Curco, David Nussinov, Ruth Aleman, Carlos TI Coarse-graining the self-assembly of beta-helical protein building blocks SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; NANOSTRUCTURE DESIGN; AMINO-ACIDS; DNA COMPLEX; MEMBRANES; BIOLOGY; SYSTEMS; MODEL AB Nanotubular structures constructed using self-assembled P-helical protein building blocks one atop the other have been coarsened to develop a mesoscopic potential that reproduces the intermolecular interaction energies provided by atomistic force-fields. The resulting potential consists of an analytical expression that depends exclusively on the distance and the relative orientation between the two interacting entities. In spite of its complexity, this coarse-grained potential reproduces satisfactorily the energetic properties of two interacting building blocks. The coarse-grained potential has been used to predict that the interaction between building blocks formed by residues 131-165 of E. coli galactoside acteyltransferase becomes repulsive when the size of the nanotube is larger than a threshold, that is, about 45 self-assembled building blocks. C1 [Curco, David] Univ Barcelona, Fac Quim, Dept Engn Quim, E-08028 Barcelona, Spain. [Nussinov, Ruth] SAIC Frederick Inc, NCI, Ctr Canc Res Nanobiol Program, Basic Res Program, Ft Detrick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sch Med, Dept Human Genet Sackler, IL-69978 Tel Aviv, Israel. [Aleman, Carlos] Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain. RP Curco, D (reprint author), Univ Barcelona, Fac Quim, Dept Engn Quim, Marti & Franques 1, E-08028 Barcelona, Spain. EM curco@angel.qui.ub.es; carlos.aleman@upc.es FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 26 TC 9 Z9 9 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 20 PY 2007 VL 111 IS 50 BP 14006 EP 14011 DI 10.1021/jp075386f PG 6 WC Chemistry, Physical SC Chemistry GA 240VD UT WOS:000251615400022 PM 18027921 ER PT J AU Jiang, WY Simon, R AF Jiang, Wenyu Simon, Richard TI A comparison of bootstrap methods and an adjusted bootstrap approach for estimating the prediction error in microarray classification SO STATISTICS IN MEDICINE LA English DT Article DE bootstrap; prediction error; class prediction; microarray data; learning curve; feature selection ID GENE-EXPRESSION DATA; B-CELL LYMPHOMA; CROSS-VALIDATION AB This paper first provides a critical review on some existing methods for estimating the prediction error in classifying microarray data where the number of genes greatly exceeds the number of specimens. Special attention is given to the bootstrap-related methods. When the sample size n is small, we find that all the reviewed methods suffer from either substantial bias or variability. We introduce a repeated leave-one-out bootstrap (RLOOB) method that predicts for each specimen in the sample using bootstrap learning sets of size ln. We then propose an adjusted bootstrap (ABS) method that fits a learning curve to the RLOOB estimates calculated with different bootstrap learning set sizes. The ABS method is robust across the situations we investigate and provides a slightly conservative estimate for the prediction error. Even with small samples, it does not suffer from large upward bias as the leave-one-out bootstrap and the 0.632+bootstrap, and it does not suffer from large variability as the leave-one-out cross-validation in microarray applications. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 [Jiang, Wenyu] Concordia Univ, Dept Math & Stat, Montreal, PQ H3G 1M8, Canada. [Jiang, Wenyu; Simon, Richard] NCI, NIH, Div Canc Treatment & Diag, Biometr Res Branch, Rockville, MD 20852 USA. RP Jiang, WY (reprint author), Concordia Univ, Dept Math & Stat, 1455 Maisonneuve Blvd W, Montreal, PQ H3G 1M8, Canada. EM wjiang@mathstat.concordia.ca NR 21 TC 46 Z9 47 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 20 PY 2007 VL 26 IS 29 BP 5320 EP 5334 DI 10.1002/sim.2968 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 241HR UT WOS:000251648000007 PM 17624926 ER PT J AU Kao, S Goila-Gaur, R Miyagi, E Khan, MA Opi, S Takeuchi, H Strebel, K AF Kao, Sandra Goila-Gaur, Ritu Miyagi, Eri Khan, Mohammad A. Opi, Sandrine Takeuchi, Hiroaki Strebel, Klaus TI Production of infectious virus and degradation of APOBEC3G are separable functional properties of human immunodeficiency virus type 1 Vif SO VIROLOGY LA English DT Article DE Vif; APOBEC3G; protein degradation; virus-host interactions ID ANTIVIRAL PROTEIN APOBEC3G; EDITING ENZYME APOBEC3G; HIV-1 VIRIONS; VIRAL INFECTIVITY; STRESS GRANULES; T-CELLS; RNA; PROTEASOME; DNA; EXPRESSION AB HIV-1 Vif regulates viral infectivity by inhibiting the encapsidation of APOBEC3G (APO3G) through proteasomal degradation of the protein. Here we compared various Vif proteins for their ability to induce APO3G degradation and rescue viral infectivity. We found that Vif expressed from proviral vectors caused relatively inefficient degradation of APO3G in HeLa cells yet was very effective in inhibiting APO3G's antiviral activity. On the other hand, Vif expressed autonomously from a codon-optimized vector caused very efficient APO3G degradation and also effectively inhibited APO3G's antiviral effects. In contrast, a Vif chimera containing an N-terminal fluorescent tag efficiently induced APO3G degradation but was unable to restore viral infectivity. The lack of a direct correlation between APO3G degradation and rescue of viral infectivity suggests that these two properties of Vif are functionally separable. Our data imply that intracellular degradation of APO3G may not be the sole activity of Vif required for the production of infectious virions from APO3G-expressing cells. Published by Elsevier Inc. C1 NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bldg 4,Room 310,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA. EM kstrebel@nih.gov RI Takeuchi, Hiroaki/F-9728-2012 FU Intramural NIH HHS [Z01 AI000669-15] NR 43 TC 25 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 20 PY 2007 VL 369 IS 2 BP 329 EP 339 DI 10.1016/j.virol.2007.08.005 PG 11 WC Virology SC Virology GA 235VU UT WOS:000251263200010 PM 17825339 ER PT J AU Bar-Magen, T Spencer, E Patton, JT AF Bar-Magen, Tamara Spencer, Eugenio Patton, John T. TI An ATPase activity associated with the rotavirus phosphoprotein NSP5 SO VIROLOGY LA English DT Article DE rotavirus; phosphoprotein; NSP5; ATPase ID NONSTRUCTURAL PROTEIN NSP5; DOUBLE-STRANDED-RNA; TRIPHOSPHATASE ACTIVITIES; CRYOELECTRON MICROSCOPY; 3-DIMENSIONAL STRUCTURE; ENDOPLASMIC-RETICULUM; GENOME REPLICATION; PHOSPHORYLATION; HELICASE; HYPERPHOSPHORYLATION AB Interactions between NSP5 and NSP2 drive the formation of viroplasms, sites of genome replication and packaging in rotavirus-infected cells. The serine-threonine-rich NSP5 transitions between hypo- and hyper-phosphorylated isomers during the replication cycle. In this study, we determined that purified recombinant NSP5 has a Mg2+-dependent ATP-specific triphosphatase activity that generates free ADP and Pi (V-max Of 19.33 fmol of product/min/pmol of enzyme). The ATPase activity was correlated with low levels of NSP5 phosphorylation, suggestive of a possible link between ATP hydrolysis and an NSP5 autokinase activity. Mutagenesis showed that the critical residue (Ser67) needed for NSP5 hyperphosphorylation by cellular casein kinase-like enzymes has no role in the ATPase or autokinase activities of NSP5. Through its NDP kinase activity, the NSP2 octamer may support NSP5 phosphorylation by creating a constant source of ATP molecules for the autokinase activity of NSP5 and for cellular kinases associated with NSP5. (c) 2007 Elsevier Inc. All rights reserved. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Santiago Chile, Fac Quim & Biol, Virol Lab, Santiago, Chile. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 50 S Drive,MSC 8026,Room 6314, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000754-12] NR 45 TC 8 Z9 9 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 20 PY 2007 VL 369 IS 2 BP 389 EP 399 DI 10.1016/j.virol.2007.07.029 PG 11 WC Virology SC Virology GA 235VU UT WOS:000251263200015 PM 17825341 ER PT J AU Pinsky, PF AF Pinsky, Paul F. TI Claims of sex-gene interactions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID DISEASES C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 19 PY 2007 VL 298 IS 23 BP 2741 EP 2742 DI 10.1001/jama.298.23.2741-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 242HK UT WOS:000251716000017 PM 18165666 ER PT J AU Lai, C Lin, X Chandran, J Shim, H Yang, WJ Cai, HB AF Lai, Chen Lin, Xian Chandran, Jayanth Shim, Hoon Yang, Wan-Jou Cai, Huaibin TI The G59S mutation in p150(glued) causes dysfunction of dynactin in mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dynactin; dynein; p150(glued); motor neuron disease; mouse model; ALS ID MOTOR-NEURON DEGENERATION; CYTOPLASMIC DYNEIN; AXONAL-TRANSPORT; SOD1(G93A) MICE; DCTN1 GENE; PROTEINS; NEUROFILAMENTS; MICROTUBULES; DISEASE; ALS AB The G59S missense mutation at the conserved microtubule-binding domain of p150(glued), a major component of dynein/dynactin complex, has been linked to an autosomal dominant form of motor neuron disease (MND). To study how this mutation affects the function of the dynein/dynactin complex and contributes to motor neuron degeneration, we generated p150(glued) G59S knock-in mice. We found that the G59S mutation destabilizes p150(glued) and disrupts the function of dynein/dynactin complex, resulting in early embryonic lethality of homozygous knock-in mice. Heterozygous knock-in mice, which developed normally, displayed MND-like phenotypes after 10 months of age, including excessive accumulation of cytoskeletal and synaptic vesicle proteins at neuromuscular junctions, loss of spinal motor neurons, increase of reactive astrogliosis, and shortening of gait compared with wild-type littermates and age-matched p150(glued) heterozygous knock-out mice. Our findings indicate that the G59S mutation in p150(glued) abrogates the normal function of p150(glued) and accelerates motor neuron degeneration. C1 [Lai, Chen; Lin, Xian; Chandran, Jayanth; Shim, Hoon; Yang, Wan-Jou; Cai, Huaibin] NIA, Natl Inst Hlth, Neurogenet Lab, Unit Transgenesis, Bethesda, MD 20892 USA. [Lin, Xian] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Anat, Guangzhou 510089, Peoples R China. RP Cai, HB (reprint author), NIA, Natl Inst Hlth, Neurogenet Lab, Unit Transgenesis, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA. EM caih@mail.nih.gov RI Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 FU Intramural NIH HHS [Z01 AG000959-04, Z99 AG999999] NR 36 TC 64 Z9 65 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 19 PY 2007 VL 27 IS 51 BP 13982 EP 13990 DI 10.1523/JNEUROSCI.4226-07.2007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 245BZ UT WOS:000251910800009 PM 18094236 ER PT J AU McKenna, CE Kashemirov, BA Upton, TG Batra, VK Goodman, MF Pedersen, LC Beard, WA Wilson, SH AF McKenna, Charles E. Kashemirov, Boris A. Upton, Thomas G. Batra, Vinod K. Goodman, Myron F. Pedersen, Lars C. Beard, William A. Wilson, Samuel H. TI (R)-beta,gamma-fluoromethylene-dGTP-DNA ternary complex with DNA polymerase beta SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID FLUORINE; DOCKING; CANCER; 5'-TRIPHOSPHATES; CONSEQUENCES; PHOSPHATES; STABILITY; CHEMISTRY; MECHANISM; AUTODOCK AB beta,gamma-Fluoromethylene analogues of nucleotides are generally considered to be useful mimics of the natural substrates for DNA polymerases, but direct structural evidence defining their active site interactions has not been available. In addition, the effect of introducing a new chiral center (the CHF carbon) has been unexplored. We report here structural studies of the diastereomeric beta,gamma- CHF analogues (R, 3; S, 4) of dGTP interacting with the active site of DNA pol beta, a repair enzyme that plays an important role in base excision repair (BER) and oncogenesis. The conjugation of dGMP 5'-morpholidate with a tetrabutylammonium salt of (fluoromethylene)bisphosphonic acid (6b, prepared like its difluoro analogue 7b via fluorination of tetraisopropyl methylenebisphosphonate carbanion with Selectfluor) gives a 1:1 mixture of 3 and 4 (by F-19 NMR, pH 10). The beta,gamma-CF2 (2) and beta,gamma-CH2 (1) dGTP analogues were also synthesized. Crystallization from a solution containing 3 + 4 together with a preformed DNA pol beta complex of a 16-mer template DNA and a one-nucleotide gapped primer produced crystals containing the (R)-analogue 3, as shown by the X-ray structure (2.1 angstrom), which revealed a 3.0 angstrom (bonding) distance between a guanidine N of Arg 183 and the CHF fluorine atom. Ligand docking simulations of 3 vs 4 using Autodock 3.0 predicted that both 3 and 4 can adopt an overall orientation closely overlaying that of dGTP itself in the active site; however, a polar C-F center dot center dot Arg183 bonding interaction is favored only with 3. A similar orientation of one fluorine atom in 2 is observed. The results suggest that introduction of a single fluorine atom at the bridging carbon atom of a beta,gamma-methylene-dNTP analogue may enable a new, stereospecific interaction within the pre-organized active site complex. C1 [McKenna, Charles E.; Kashemirov, Boris A.; Upton, Thomas G.; Goodman, Myron F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. [Batra, Vinod K.; Pedersen, Lars C.; Beard, William A.; Wilson, Samuel H.] NIEHS, NIH, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP McKenna, CE (reprint author), Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. EM mckenna@usc.edu RI Upton, Thomas/E-3749-2012 FU Intramural NIH HHS [Z01 ES050158-11, Z01 ES050159-11]; NCI NIH HHS [U19 CA105010, 5-U19-CA105010] NR 37 TC 39 Z9 39 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 19 PY 2007 VL 129 IS 50 BP 15412 EP + DI 10.1021/ja072127v PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 240IS UT WOS:000251581900001 PM 18031037 ER PT J AU Hjalgrim, H Edgren, G Rostgaard, K Reilly, M Tran, TN Titlestad, KE Shanwell, A Jersild, C Adami, J Wikman, A Gridley, G Wideroff, L Nyren, O Melbye, M AF Hjalgrim, Henrik Edgren, Gustaf Rostgaard, Klaus Reilly, Marie Tran, Trung Nam Titlestad, Kjell Einar Shanwell, Agneta Jersild, Casper Adami, Johanna Wikman, Agneta Gridley, Gloria Wideroff, Louise Nyren, Oiof Melbye, Mads TI Cancer incidence in blood transfusion recipients SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NON-HODGKINS-LYMPHOMA; FRANCISCO BAY AREA; RISK-FACTOR; POPULATION; TRANSMISSION; MORBIDITY; HISTORY; COHORT; DONORS; WOMEN AB Background Blood transfusions may influence the recipients' cancer risks both through transmission of biologic agents and by modulation of the immune system. However, cancer occurrence in transfusion recipients remains poorly characterized. Methods We used computerized files from Scandinavian blood banks to identify a cohort of 888843 cancer-free recipients transfused after 1968. The recipients were followed from first registered transfusion until the date of death, emigration, cancer diagnosis, or December 31, 2002, whichever came first. Relative risks were expressed as ratios of the observed to the expected numbers of cancers, that is, standardized incidence ratios (SIRs), using incidence rates for the general Danish and Swedish populations as a reference. All statistical tests were two-sided. Results During 5652918 person-years of follow-up, 80990 cancers occurred in the transfusion recipients, corresponding to a SIR of 1.45 (95% confidence interval [CI] = 1.44 to 1.46). The SIR for cancer overall decreased from 5.36 (95% CI = 5.29 to 5.43) during the first 6 months after transfusion to 1.10 or less for follow-up periods more than 2 years after the transfusion. However, the standardized incidence ratios for cancers of the tongue, mouth, pharynx, esophagus, liver, and respiratory and urinary tracts and for squamous cell skin carcinoma remained elevated beyond 10 years after the transfusion. Conclusions The marked increase in cancer risk shortly after a blood transfusion may reflect the presence of undiagnosed occult cancers with symptoms that necessitated the blood transfusion. The continued increased risk of tobacco- and alohol-related cancers suggests that lifestyle and other risk factors related to conditions prompting transfusion rather than transfusion-related exposures per se are important to the observed cancer occurrence in the recipients. C1 [Hjalgrim, Henrik; Rostgaard, Klaus; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Edgren, Gustaf; Reilly, Marie; Tran, Trung Nam; Adami, Johanna; Nyren, Oiof] Karolinska Inst, Stockholm, Sweden. [Tran, Trung Nam] Merck Res Labs, Dept Epidemiol, Philadelphia, PA USA. [Titlestad, Kjell Einar] Odense Univ Hosp, Dept Clin Immunol, DK-5000 Odense, Denmark. [Shanwell, Agneta; Wikman, Agneta] Karolinska Univ Hosp, Dept Clin Immunol & Transfus Med, Stockholm, Sweden. [Jersild, Casper] Aarhus Univ Hosp, Dept Clin Immunol, DK-8000 Aarhus, Denmark. [Adami, Johanna] Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden. [Gridley, Gloria] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wideroff, Louise] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Hjalgrim, H (reprint author), Statens Serum Inst, Dept Epidemiol Res, Artillerivej 5, DK-2300 Copenhagen, Denmark. EM hhj@ssi.dk RI Hernandez, Jessica/G-6527-2011; Edgren, Gustaf/F-4013-2014; OI Edgren, Gustaf/0000-0002-2198-4745; Rostgaard, Klaus/0000-0001-6220-9414 FU NCI NIH HHS [N01-CP-21175] NR 43 TC 26 Z9 26 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 19 PY 2007 VL 99 IS 24 BP 1864 EP 1874 DI 10.1093/jnci/djm248 PG 11 WC Oncology SC Oncology GA 245IL UT WOS:000251928200009 PM 18073377 ER PT J AU Reddy, NM Kleeberger, SR Yamamoto, M Kensler, TW Scollick, C Biswal, S Reddy, SP AF Reddy, Narsa M. Kleeberger, Steven R. Yamamoto, Masayuki Kensler, Thomas W. Scollick, Catherine Biswal, Shyam Reddy, Sekhar P. TI Genetic dissection of the Nrf2-dependent redox signaling-regulated transcriptional programs of cell proliferation and cytoprotection SO PHYSIOLOGICAL GENOMICS LA English DT Article DE oxidative stress; antioxidants; lung; glutathione ID OXIDATIVE STRESS; NRF2; LUNG; RECEPTOR; GLUTATHIONYLATION; INFLAMMATION; ACTIVATION; EXPRESSION; PROTECTS; BETA AB The beta zipper (bZip) transcription factor, nuclear factor erythroid 2, like 2 (Nrf2), acting via an antioxidant/electrophile response element, regulates the expression of several antioxidant enzymes and maintains cellular redox homeostasis. Nrf2 deficiency diminishes pulmonary expression of several antioxidant enzymes, rendering them highly susceptible to various mouse models of prooxidant-induced lung injury. We recently demonstrated that Nrf2 deficiency impairs primary cultured pulmonary epithelial cell proliferation and greatly enhances sensitivity to prooxidant-induced cell death. Glutathione (GSH) supplementation rescued cells from these defects associated with Nrf2 deficiency. To further delineate the mechanisms by which Nrf2, via redox signaling, regulates cellular protection and proliferation, we compared the global expression profiling of Nrf2-deficient cells with and without GSH supplementation. We found that GSH regulates the expression of various networks of transcriptional programs including 1) several antioxidant enzymes involved in cellular detoxification of reactive oxygen species and recycling of thiol status and 2) several growth factors, growth factor receptors, and integrins that are critical for cell growth and proliferation. We also found that Nrf2 deficiency enhances the expression levels of several genes encoding proinflammatory cytokines; however, GSH supplementation markedly suppressed their expression. Collectively, these findings uncover an important insight into the nature of genes regulated by Nrf2-dependent redox signaling through GSH that are involved in cellular detoxification and proliferation. C1 [Reddy, Narsa M.; Kensler, Thomas W.; Scollick, Catherine; Biswal, Shyam; Reddy, Sekhar P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. [Kleeberger, Steven R.] Natl Inst Hlth, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Yamamoto, Masayuki] Tohoku Univ, Grad Sch Med, Dept Biochem Med, Sendai, Miyagi, Japan. RP Reddy, NM (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Rm E7547,615 N Wolfe St, Baltimore, MD 21205 USA. EM sreddy@jhsph.edu RI Yamamoto, Masayuki/A-4873-2010; Kensler, Thomas/D-8686-2014 OI Kensler, Thomas/0000-0002-6676-261X FU NCI NIH HHS [CA-94076]; NHLBI NIH HHS [HL-66109, HL-81205, P50-HL-073994, R01 HL081205, R01 HL081205-03]; NIEHS NIH HHS [P30-ES-038819] NR 32 TC 61 Z9 64 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD DEC 19 PY 2007 VL 32 IS 1 BP 74 EP 81 DI 10.1152/physiolgenomics.00126.2007 PG 8 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 243FP UT WOS:000251780900008 PM 17895394 ER PT J AU Huang, AM Rudelius, M Sharan, S McAllister, JM Raffeld, M Christenson, LK Sterneck, E AF Huang, A-Mei Rudelius, Martina Sharan, Shikha McAllister, Jan M. Raffeld, Mark Christenson, Lane K. Sterneck, Esta TI The Cebpd (C/EBP delta) Gene Is Induced by Luteinizing Hormones in Ovarian Theca and Interstitial Cells But Is Not Essential for Mouse Ovary Function SO PLOS ONE LA English DT Article AB The CCAAT/enhancer binding protein (CEBP) family of transcription factors includes five genes. In the ovary, both Cebpa and Cebpb are essential for granulosa cell function. In this study we have explored the role of the Cebpd gene in ovarian physiology by expression and functional studies. Here we report that Cebpd (C/EBPd) is expressed in the mouse ovary in a highly restricted temporal and spatial pattern. In response to luteinizing hormone (LH/hCG), CEBPD expression is transiently induced in interstitial cells and in theca cells of follicles from the primary to pre-ovulatory stage, and overlaps in part with expression of the alpha-smooth muscle actin protein. Efficient down-regulation of CEBPD was dependent on a functional Cebpb gene. Proliferating human theca cells in culture also express Cebpd. Cells from patients with polycystic ovarian syndrome (PCOS) exhibited higher Cebpd expression levels. However, deletion of Cebpd in mice had no overt effect on ovarian physiology and reproductive function. Very little is known at present about the molecular mechanisms underlying theca/interstitial cell functions. The expression pattern of CEBPD reported here identifies a novel functional unit of mouse theca cells of primary through tertiary follicles responding to LH/hCG together with a subset of interstitial cells. This acute stimulation of CEBPD expression may be exploited to further characterize the hormonal regulation and function of theca and interstitial cells. C1 [Huang, A-Mei; Sharan, Shikha; Sterneck, Esta] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Rudelius, Martina; Raffeld, Mark] NCI, Pathol Lab, Bethesda, MD 20892 USA. [McAllister, Jan M.] Penn State Univ, Dept Cellular & Mol Physiol, Coll Med, Hershey, PA USA. [Christenson, Lane K.] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66103 USA. RP Sterneck, E (reprint author), NCI, Ctr Canc Res, Frederick, MD 21701 USA. EM sterneck@ncifcrf.gov RI Christenson, Lane/G-6435-2013 FU Intramural Research Program of the NIH; National Cancer Institute; National Institutes of Child Health and Human Development [HD045519] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, and the National Institutes of Child Health and Human Development (HD045519; L.K.C). NR 37 TC 7 Z9 7 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 19 PY 2007 VL 2 IS 12 AR e1334 DI 10.1371/journal.pone.0001334 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JF UT WOS:000207459600018 PM 18092000 ER PT J AU Ma, X Liu, YH Gowen, BB Graviss, EA Clark, AG Musser, JM AF Ma, Xin Liu, Yuhua Gowen, Brian B. Graviss, Edward A. Clark, Andrew G. Musser, James M. TI Full-Exon Resequencing Reveals Toll-Like Receptor Variants Contribute to Human Susceptibility to Tuberculosis Disease SO PLOS ONE LA English DT Article AB Tuberculosis (TB) is the leading cause of death worldwide due to an infectious agent. Data have accumulated over decades suggesting that variability in human susceptibility to TB disease has a genetic component. Toll-like receptors (TLRs) play a critical role in initiating the innate immune response to many pathogens in mouse models, but little is known about their role in human infections. Human TLRs have been reported to recognize mycobacterial antigens and initiate an immune response. We tested the hypothesis that amino acid-altering polymorphisms in five TLRs were associated with susceptibility to TB disease using a population-based case-control study with 1,312 adult TB patients and controls. Full-coding region sequencing of the five TLR genes in all 1,312 subjects yielded a data set in excess of 16 Mb. Rare nonsynonymous polymorphisms in TLR6-TLR1-TLR10 were significantly overrepresented among African-American TB cases compared with ethnically-matched control subjects. Common nonsynonymous polymorphisms in TLR6-TLR1-TLR10 also were significantly associated with TB disease in certain ethnic groups. Among African Americans, homozygotes for the common-variant haplotype TLR1-248S, TLR1-6021, and TLR6-249S had a significantly increased TB disease risk. A transmission/disequilibrium test on an independent sample found that the TLR1-248S variant was preferentially transmitted to diseased children, thereby confirming disease association. These results are consistent with recent reports implicating TLR1 variants, including TLR1-602, in significantly altered innate immune responses. Also consistent with disease association, rare TLR6 variants were defective in their ability to mediate NF-kappa B signal transduction in transfected human cells. Taken together, the data suggest that variant TLRs contribute to human susceptibility to TB disease. Extensive full-exon resequencing was critical for revealing new information about the role of TLRs in human-pathogen interactions and the genetic basis of innate immune function. C1 [Liu, Yuhua; Gowen, Brian B.; Musser, James M.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Ma, Xin; Graviss, Edward A.] Baylor Coll Med, Dept Pathol, Ctr Human Bacterial Pathogenesis, Houston, TX 77030 USA. [Clark, Andrew G.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY USA. [Musser, James M.] Methodist Hosp, Res Inst, Ctr Human Mol & Translat Infect Dis Res, Houston, TX 77030 USA. RP Musser, JM (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM jmmusser@tmhs.org FU The Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institute of Health FX The Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health NR 65 TC 106 Z9 111 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 19 PY 2007 VL 2 IS 12 AR e1318 DI 10.1371/journal.pone.0001318 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JF UT WOS:000207459600006 PM 18091991 ER PT J AU Quignon, P Herbin, L Cadieu, E Kirkness, EF Hedan, B Mosher, DS Galibert, F Andre, C Ostrander, EA Hitte, C AF Quignon, Pascale Herbin, Laetitia Cadieu, Edouard Kirkness, Ewen F. Hedan, Benoit Mosher, Dana S. Galibert, Francis Andre, Catherine Ostrander, Elaine A. Hitte, Christophe TI Canine Population Structure: Assessment and Impact of Intra-Breed Stratification on SNP-Based Association Studies SO PLOS ONE LA English DT Article AB Background. In canine genetics, the impact of population structure on whole genome association studies is typically addressed by sampling approximately equal numbers of cases and controls from dogs of a single breed, usually from the same country or geographic area. However one way to increase the power of genetic studies is to sample individuals of the same breed but from different geographic areas, with the expectation that independent meiotic events will have shortened the presumed ancestral haplotype around the mutation differently. Little is known, however, about genetic variation among dogs of the same breed collected from different geographic regions. Methodology/Principal Findings. In this report, we address the magnitude and impact of genetic diversity among common breeds sampled in the U.S. and Europe. The breeds selected, including the Rottweiler, Bernese mountain dog, flat-coated retriever, and golden retriever, share susceptibility to a class of soft tissue cancers typified by malignant histiocytosis in the Bernese mountain dog. We genotyped 722 SNPs at four unlinked loci (between 95 and 271 per locus) on canine chromosome 1 (CFA1). We showed that each population is characterized by distinct genetic diversity that can be correlated with breed history. When the breed studied has a reduced intra-breed diversity, the combination of dogs from international locations does not increase the rate of false positives and potentially increases the power of association studies. However, over-sampling cases from one geographic location is more likely to lead to false positive results in breeds with significant genetic diversity. Conclusions. These data provide new guidelines for association studies using purebred dogs that take into account population structure. C1 [Quignon, Pascale; Cadieu, Edouard; Mosher, Dana S.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Herbin, Laetitia; Hedan, Benoit; Galibert, Francis; Andre, Catherine; Hitte, Christophe] Univ Rennes 1, CNRS, UMR Genet & Dev 6061, IFR140, CS-34317 Rennes, France. [Kirkness, Ewen F.] J Craig Venter Inst, Rockville, MD USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov; hitte@univ-rennes1.fr OI Ostrander, Elaine/0000-0001-6075-9738 FU American Kennel Club Canine Health Foundation; French Centre National de la Recherche Scientifique (CNRS); National Human Genome Research Institute; National Institutes of Health FX We would like to thank the American Kennel Club Canine Health Foundation, the French Centre National de la Recherche Scientifique (CNRS) and the intramural program of the National Human Genome Research Institute of the National Institutes of Health for supporting this work. NR 38 TC 37 Z9 39 U1 0 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 19 PY 2007 VL 2 IS 12 AR e1324 DI 10.1371/journal.pone.0001324 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JF UT WOS:000207459600012 PM 18091995 ER PT J AU Lauer, MS Pothier, CE Magid, DJ Smith, SS Kaftan, MW AF Lauer, Michael S. Pothier, Claire E. Magid, David J. Smith, S. Scott Kaftan, Michael W. TI An externally validated model for predicting long-term survival after exercise treadmill testing in patients with suspected coronary artery disease and a normal electrocardiogram SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HEART-RATE RECOVERY; ALL-CAUSE MORTALITY; PROGNOSTIC VALUE; SCORE; DEATH; SYMPTOMS; ECG AB Background: The exercise treadmill test is recommended for risk stratification among patients with intermediate to high pretest probability of coronary artery disease. Posttest risk stratification is based on the Duke treadmill score, which includes only functional capacity and measures of ischemia. Objective: To develop and externally validate a post-treadmill test, multivariable mortality prediction rule for adults with suspected coronary artery disease and normal electrocardiograms. Design: Prospective cohort study conducted from September 1990 to May 2004. Setting: Exercise treadmill laboratories in a major medical center (derivation set) and a separate HMO (validation set). Patients: 33 268 patients in the derivation set and 5821 in the validation set. All patients had normal electrocardiograms and were referred for evaluation of suspected coronary artery disease. Measurements: The derivation set patients were followed for a median of 6.2 years. A nomogram-illustrated model was derived on the basis of variables easily obtained in the stress laboratory, including age; sex; history of smoking, hypertension, diabetes, or typical angina; and exercise findings of functional capacity, ST-segment changes, symptoms, heart rate recovery, and frequent ventricular ectopy in recovery. Results: The derivation data set included 1619 deaths. Although both the Duke treadmill score and our nomogram-illustrated model were significantly associated with death (P < 0.001), the nomogram was better at discrimination (concordance index for right-censored data, 0.83 vs. 0.73) and calibration. We reclassified many patients with intermediate- to high-risk Duke treadmill scores as low risk on the basis of the nomogram. The model also predicted 3-year mortality rates well in the validation set: Based on an optimal cut-point for a negative predictive value of 0.97, derivation and validation rates were, respectively, 1.7% and 2.5% below the cut-point and 25% and 29% above the cut-point. Limitations: Blood test-based measures or left ventricular ejection fraction were not included. The nomogram can be applied only to patients with a normal electrocardiogram. Clinical utility remains to be tested. Conclusion: A simple nomogram based on easily obtained pretest and exercise test variables predicted all-cause mortality in adults with suspected coronary artery disease and normal electrocardiograms. C1 [Lauer, Michael S.; Pothier, Claire E.; Magid, David J.; Smith, S. Scott; Kaftan, Michael W.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Lauer, Michael S.; Pothier, Claire E.; Magid, David J.; Smith, S. Scott; Kaftan, Michael W.] Cleveland Clin Fdn, Cleveland, OH USA. [Lauer, Michael S.; Pothier, Claire E.; Magid, David J.; Smith, S. Scott; Kaftan, Michael W.] NHLBI, Bethesda, MD USA. [Lauer, Michael S.; Pothier, Claire E.; Magid, David J.; Smith, S. Scott; Kaftan, Michael W.] Kaiser Permanente, Denver, CO USA. RP Lauer, MS (reprint author), NHLBI, Div Prevent & Populat Sci, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM lauerm@nhlbi.nih.gov RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 FU NHLBI NIH HHS [HL072771, HL66004] NR 30 TC 36 Z9 38 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 18 PY 2007 VL 147 IS 12 BP 821 EP 828 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 243HO UT WOS:000251787600001 PM 18087052 ER PT J AU Schmeisser, H Gorshkova, I Brown, PH Kontsek, P Schuck, P Zoon, KC AF Schmeisser, Hana Gorshkova, Inna Brown, Patrick H. Kontsek, Peter Schuck, Peter Zoon, Kathryn C. TI Two interferons alpha influence each other during their interaction with the extracellular domain of human type interferon receptor subunit 2 SO BIOCHEMISTRY LA English DT Article ID MUTATIONAL ANALYSIS; BINDING INTERFACE; LIGAND-BINDING; I INTERFERONS; IFN-BETA; RECEPTOR; PROTEIN; IFN-ALPHA-2; AFFINITY; IDENTIFICATION AB The interaction between two human interferons alpha (IFN-alpha s) and the extracellular (EC) domain of human type I IFN receptor subunit 2 (IFNAR2) was analyzed. Previous experiments using Daudi cells showed that IFN-alpha 21b and some IFN-alpha hybrids (made from IFN-alpha 2c and 21b) competed poorly for the IFN-alpha 2b binding site. This study examined the causes of the poor competition between these IFN-alpha s. IFN-alpha 2c and the IFN hybrid CM3 {IFN-alpha 21b(1-75)(81-95)/IFN-alpha 2c(76-80) (96-166), Y86K} were selected for this study based on their cell binding and biological properties. Competitive binding ELISA, native electrophoresis followed by Western blot, electrospray ionization mass spectrometry (ESI-MS), surface plasmon resonance biosensor (SPR) analysis, as well as neutralization of antiproliferative activities on Daudi cells in the presence of soluble IFNAR2-EC show evidence that each of the described IFN-alpha subtypes affected the binding of the other IFN-alpha to IFNAR2-EC by affecting the stability of the complex, i.e., dissociation of the complex. Moreover, native electrophoresis with different IFNAR2-EC mutants showed that IFN-alpha 2c and CM3 utilize different amino acids in the binding domain of IFNAR2-EC. In addition to that, analytical ultracentrifugation (AUC) revealed differences in the oligomeric state of the two studied interferons. Our results demonstrated that two individual IFN-alpha s interact differentially with IFNAR2-EC and influence each other during this interaction. This study contributes to the understanding of the mutual interaction between multiple IFN-alpha subtypes during the competition for binding to the receptor. C1 NIAID, NIH, Bethesda, MD 20892 USA. NIH, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. SAS, Inst Neuroimmunol, Bratislava, Slovakia. RP Schmeisser, H (reprint author), NIAID, NIH, HFM 8001,50 Ctr Dr,Bldg 50,Room 5515, Bethesda, MD 20892 USA. EM hschmeisser@niaid.nih.gov OI Schuck, Peter/0000-0002-8859-6966 FU Intramural NIH HHS [Z01 AI000944-04] NR 38 TC 7 Z9 7 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 18 PY 2007 VL 46 IS 50 BP 14638 EP 14649 DI 10.1021/bi7012036 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 239VZ UT WOS:000251547700030 PM 18027911 ER PT J AU Hu, YH Ying, H Xu, YH AF Hu, Yihong Ying, Hao Xu, Yonghua TI HF-LANa, a human homologue of Derlin family, regulating the expression of cancer-related genes promotes NIH3T3 cell transformation SO CANCER LETTERS LA English DT Article DE hF-LANa; Transformation; oncogene/proto-oncogene; tumor suppressor gene; mouse oligo cDNA expression assay ID ENDOPLASMIC-RETICULUM MEMBRANE; HEPATOCELLULAR-CARCINOMA; MISFOLDED PROTEINS; DEGRADATION; GROWTH; RB; ER; IDENTIFICATION; TUMORIGENESIS; DISLOCATION AB hF-LANa, a member of Derlin family, is a putative proto-oncogene and has a direct role in oncogenic transformation. hF-LANa over-expressed NIH3T3 cells grow 20% quicker than parent cells. Especially, hF-LANa over-expression promotes anchorage-independent growth of NIH3T3 cells in soft agar and tumorigenesis in nude mice. Analysis by cDNA microarray finds 252 up-regulated genes and 354 down-regulated genes in hF-LANa over-expressed NIH3T3 cells including 19 oncogenes/proto-oncogenes and 13 tumor suppressor genes/putative tumor suppressors. These experiments show the oncogenic transformation role of hF-LANa both in vitro and in vivo, and highlight the genes that might be related to hF-LANa's oncogenic effects. (c) 2007 Published by Elsevier Ireland Ltd. C1 [Hu, Yihong; Xu, Yonghua] Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol,Lab Mol & Cellular Oncol, Shanghai 200031, Peoples R China. [Ying, Hao] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Xu, YH (reprint author), Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol,Lab Mol & Cellular Oncol, 320 YueYang Rd, Shanghai 200031, Peoples R China. EM yhxu@sibs.ac.cn NR 32 TC 1 Z9 1 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 18 PY 2007 VL 258 IS 2 BP 171 EP 180 DI 10.1016/j.canlet.2007.08.017 PG 10 WC Oncology SC Oncology GA 244FU UT WOS:000251852600003 PM 17977649 ER PT J AU Shroff, H Galbraith, CG Galbraith, JA White, H Gillette, J Olenych, S Davidson, MW Betzig, E AF Shroff, Hari Galbraith, Catherine G. Galbraith, James A. White, Helen Gillette, Jennifer Olenych, Scott Davidson, Michael W. Betzig, Eric TI Dual-color superresolution imaging of genetically expressed probes within individual adhesion complexes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fluorescent proteins; multi-label ID FIELD FLUORESCENCE NANOSCOPY; SCANNING OPTICAL MICROSCOPY; MATRIX ADHESIONS; PROTEIN; LOCALIZATION; MULTICOLOR; TRACKING; EMITTERS; CELLS; EOSFP AB Accurate determination of the relative positions of proteins within localized regions of the cell is essential for understanding their biological function. Although fluorescent fusion proteins are targeted with molecular precision, the position of these genetically expressed reporters is usually known only to the resolution of conventional optics (approximate to 200 nm). Here, we report the use of two-color photoactivated localization microscopy (PALM) to determine the ultrastructural relationship between different proteins fused to spectrally distinct photoactivatable fluorescent proteins (PA-FPs). The nonperturbative incorporation of these endogenous tags facilitates an imaging resolution in whole, fixed cells of approximate to 20-30 nm at acquisition times of 5-30 min. We apply the technique to image different pairs of proteins assembled in adhesion complexes, the central attachment points between the cytoskeleton and the substrate in migrating cells. For several pairs, we find that proteins that seem colocalized when viewed by conventional optics are resolved as distinct interlocking nano-aggregates when imaged via PALM. The simplicity, minimal invasiveness, resolution, and speed of the technique all suggest its potential to directly visualize molecular interactions within cellular structures at the nanometer scale. C1 [Shroff, Hari; White, Helen; Betzig, Eric] Howard Hughes Med Inst, Ashburn, VA 20147 USA. [Galbraith, James A.] Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. [Galbraith, James A.] NINDS, Bethesda, MD 20892 USA. [Gillette, Jennifer] NIH, NICHHD, Bethesda, MD 20892 USA. [Olenych, Scott; Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. RP Shroff, H (reprint author), Howard Hughes Med Inst, Ashburn, VA 20147 USA. EM shroffh@janelia.hhmi.org RI Shroff, Hari/E-7247-2016 OI Shroff, Hari/0000-0003-3613-8215 FU Intramural NIH HHS NR 34 TC 280 Z9 290 U1 10 U2 101 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2007 VL 104 IS 51 BP 20308 EP 20313 DI 10.1073/pnas.0710517105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 244SG UT WOS:000251885000030 PM 18077327 ER PT J AU Nikolaev, SI Montoya-Burgos, JI Popadin, K Parand, L Margulies, EH Antonarakis, SE AF Nikolaev, Sergey I. Montoya-Burgos, Juan I. Popadin, Konstantin Parand, Leila Margulies, Elliott H. Antonarakis, Stylianos E. CA NIHISCCS Program TI Life-history traits drive the evolutionary rates of mammalian coding and noncoding genomic elements SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE constrains; generation time; genome; population size ID SLIGHTLY DELETERIOUS MUTATIONS; MOLECULAR EVOLUTION; NUCLEOTIDE SUBSTITUTION; CONSERVED SEQUENCES; NATURAL-SELECTION; POPULATION-SIZE; GENERATION TIME; DNA; IDENTIFICATION; REGIONS AB A comprehensive phylogenetic framework is indispensable for investigating the evolution of genomic features in mammals as a whole, and particularly in humans. Using the ENCODE sequence data, we estimated mammalian neutral evolutionary rates and selective pressures acting on conserved coding and noncoding elements. We show that neutral evolutionary rates can be explained by the generation time (GT) hypothesis. Accordingly, primates (especially humans), having longer GTs than other mammals, display slower rates of neutral evolution. The evolution of constrained elements, particularly of nonsynonymous sites, is in agreement with the expectations of the nearly neutral theory of molecular evolution. We show that rates of nonsynonymous substitutions (dN) depend on the population size of a species. The results are robust to the exclusion of hypermutable CpG prone sites. The average rate of evolution in conserved noncoding sequences (CNCs) is 1.7 times higher than in nonsynonymous sites. Despite this, CNCs evolve at similar or even lower rates than nonsynonymous sites in the majority of basal branches of the eutherian tree. This observation could be the result of an overall gradual or, alternatively, lineage-specific relaxation of CNCs. The latter hypothesis was supported by the finding that 3 of the 20 longest CNCs displayed significant relaxation of individual branches. This observation may explain why the evolution of CNCs fits the expectations of the nearly neutral theory less well than the evolution of nonsynonymous sites. C1 [Nikolaev, Sergey I.; Parand, Leila; Antonarakis, Stylianos E.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Montoya-Burgos, Juan I.] Univ Geneva, Dept Anim Biol, CH-1211 Geneva, Switzerland. [Popadin, Konstantin] Russian Acad Sci, Inst Informat Tranmiss Problems, Moscow 127994, Russia. [Margulies, Elliott H.; NIHISCCS Program] NIH, Genome Technol Branch, Bethesda, MD 20892 USA. [NIHISCCS Program] NIH, Intramural Sequencing Ctr, Natl Human Genom Res Inst, Bethesda, MD 20892 USA. RP Nikolaev, SI (reprint author), Univ Geneva, Sch Med, Dept Genet Med & Dev, 1 Rue Michel-Servet, CH-1211 Geneva, Switzerland. EM sergey.nikolaev@medecine.unige.ch RI Nikolaev, Sergey/F-3148-2012; Antonarakis, Stylianos/N-8866-2014 OI Antonarakis, Stylianos/0000-0001-8907-5823 FU Intramural NIH HHS NR 59 TC 57 Z9 57 U1 2 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2007 VL 104 IS 51 BP 20443 EP 20448 DI 10.1073/pnas.0705658104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 244SG UT WOS:000251885000053 PM 18077382 ER PT J AU Adermark, L Lovinger, DM AF Adermark, Louise Lovinger, David M. TI Retrograde endocannabinoid signaling at striatal synapses requires a regulated postsynaptic release step SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE anandamide; basal ganglia; synaptic plasticity; CB1 receptor ID LONG-TERM DEPRESSION; DEPOLARIZATION-INDUCED SUPPRESSION; ENDOGENOUS CANNABINOID ANANDAMIDE; HUMAN ENDOTHELIAL-CELLS; SYNAPTIC PLASTICITY; MEMBRANE-TRANSPORT; NITRIC-OXIDE; DOPAMINE; MODULATION; ACTIVATION AB Endocannabinoids (eCBs) mediate short- and long-term depression of synaptic strength by retrograde transsynaptic signaling. Previous studies have suggested that an eCB mobilization or release step in the postsynaptic neuron is involved in this retrograde signaling. However, it is not known whether this release process occurs automatically upon eCB synthesis or whether it is regulated by other synaptic factors. To address this issue, we loaded postsynaptic striatal medium spiny neurons (MSNs) with the eCBs anandamide (AEA) or 2-arachidonoylglycerol and determined the conditions necessary for presynaptic inhibition. We found that presynaptic depression of glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) induced by postsynaptic eCB loading required a certain level of afferent activation that varied between the different synaptic types. Synaptic depression at excitatory synapses was temperature-dependent and blocked by the eCB membrane transport blockers, VDM11 and UCM707, but did not require activation of metabotropic glutamate receptors, L-calcium channels, nitric oxide, voltage-activated Na+ channels, or intracellular calcium. Application of the CB1R antagonist, AM251, after depression was established, reversed the decrease in EPSC, but not in IPSC, amplitude. Direct activation of the CB1 receptor by WIN 55,212-2 initiated synaptic depression that was independent of afferent stimulation. These findings indicate that retrograde eCB signaling requires a postsynaptic release step involving a transporter or carrier that is activated by afferent stimulation/synaptic activation. C1 [Adermark, Louise; Lovinger, David M.] NIH, Natl Inst Alcohol Abuse & Alcoholism, Lab Integrat Neurosci, Sect Synap Pharmacol, Bethesda, MD 20892 USA. RP Lovinger, DM (reprint author), NIH, Natl Inst Alcohol Abuse & Alcoholism, Lab Integrat Neurosci, Sect Synap Pharmacol, Bldg 10, Bethesda, MD 20892 USA. EM lovindav@mail.nih.gov RI Adermark, Louise/D-2297-2014 OI Adermark, Louise/0000-0002-7165-9908 FU Intramural NIH HHS NR 48 TC 60 Z9 61 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2007 VL 104 IS 51 BP 20564 EP 20569 DI 10.1073/pnas.0706873104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 244SG UT WOS:000251885000074 PM 18077376 ER PT J AU Kriegeskorte, N Formisano, E Sorger, B Goebel, R AF Kriegeskorte, Nikolaus Formisano, Elia Sorger, Bettina Goebel, Rainer TI Individual faces elicit distinct response patterns in human anterior temporal cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fMRI; information-based; population code ID HUMAN VISUAL-CORTEX; HUMAN NEURAL SYSTEM; CONGENITAL PROSOPAGNOSIA; OCCIPITOTEMPORAL CORTEX; INFEROTEMPORAL CORTEX; DETAILED EXPLORATION; CORTICAL REGION; FUNCTIONAL MRI; FUSIFORM GYRUS; FMRI EVIDENCE AB Visual face identification requires distinguishing between thousands of faces we know. This computational feat involves a network of brain regions including the fusiform face area (FIFA) and anterior inferotemporal cortex (aIT), whose roles in the process are not well understood. Here, we provide the first demonstration that it is possible to discriminate cortical response patterns elicited by individual face images with high-resolution functional magnetic resonance imaging (fMRI). Response patterns elicited by the face images were distinct in aIT but not in the FFA. Individual-level face information is likely to be present in both regions, but our data suggest that it is more pronounced in aIT. One interpretation is that the FIFA detects faces and engages aIT for identification. C1 [Kriegeskorte, Nikolaus] Natl Inst Mental Hlth, Lab Brain Cognit, Sect Funct Imaging Methods, Bethesda, MD 20892 USA. [Formisano, Elia; Sorger, Bettina; Goebel, Rainer] Univ Maastricht, Fac Psychol, Dept Cognit Neurosci, NL-6200 MD Maastricht, Netherlands. RP Kriegeskorte, N (reprint author), Natl Inst Mental Hlth, Lab Brain Cognit, Sect Funct Imaging Methods, Bethesda, MD 20892 USA. EM kriegeskorten@mail.nih.gov OI Kriegeskorte, Nikolaus/0000-0001-7433-9005 FU Intramural NIH HHS NR 81 TC 246 Z9 249 U1 1 U2 23 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2007 VL 104 IS 51 BP 20600 EP 20605 DI 10.1073/pnas.0705654104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 244SG UT WOS:000251885000080 PM 18077383 ER PT J AU Dundr, M Ospina, JK Sung, MH John, S Upender, M Ried, T Hager, GL Matera, AG AF Dundr, Miroslav Ospina, Jason K. Sung, Myong-Hee John, Sam Upender, Madhvi Ried, Thomas Hager, Gordon L. Matera, A. Gregory TI Actin-dependent intranuclear repositioning of an active gene locus in vivo SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CAJAL BODIES; LAMPBRUSH CHROMOSOMES; CHROMATIN DYNAMICS; INTERPHASE NUCLEI; HISTONE GENES; COILED BODIES; SPHERE LOCI; HUMAN-CELLS; ASSOCIATION; BODY AB Although bulk chromatin is thought to have limited mobility within the interphase eukaryotic nucleus, directed long-distance chromosome movements are not unknown. Cajal bodies (CBs) are nuclear sub-organelles that nonrandomly associate with small nuclear RNA ( snRNA) and histone gene loci in human cells during interphase. However, the mechanism responsible for this association is uncertain. In this study, we present an experimental system to probe the dynamic interplay of CBs with a U2 snRNA target gene locus during transcriptional activation in living cells. Simultaneous four-dimensional tracking of CBs and U2 genes reveals that target loci are recruited toward relatively stably positioned CBs by long-range chromosomal motion. In the presence of a dominant-negative mutant of beta-actin, the repositioning of activated U2 genes is markedly inhibited. This supports a model in which nuclear actin is required for these rapid, long-range chromosomal movements. C1 Rosalind Franklin Univ Med & Sci, Dept Cell Biol, N Chicago, IL 60064 USA. [Ospina, Jason K.; Matera, A. Gregory] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Sung, Myong-Hee; John, Sam; Hager, Gordon L.] NIH, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. [Upender, Madhvi; Ried, Thomas] Natl Canc Inst, Ctr Canc Res, NIH, Genet Branch, Bethesda, MD 20892 USA. [Matera, A. Gregory] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Matera, A. Gregory] Univ N Carolina, Program Mol Biol & Biotechnol, Chapel Hill, NC 27599 USA. RP Dundr, M (reprint author), Rosalind Franklin Univ Med & Sci, Dept Cell Biol, N Chicago, IL 60064 USA. EM mirek.dundr@rosalindfranklin.edu; agmatera@email.unc.edu OI Matera, A. Gregory/0000-0002-6406-0630 FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM053034, R01-GM53034, T32 GM008613, T32-GM08613]; NINDS NIH HHS [R01 NS041617, R01-NS41617] NR 23 TC 166 Z9 171 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 17 PY 2007 VL 179 IS 6 BP 1095 EP 1103 DI 10.1083/jcb.200710058 PG 9 WC Cell Biology SC Cell Biology GA 242AQ UT WOS:000251697300004 PM 18070915 ER PT J AU Jablonska, B Aguirre, A Vandenbosch, R Belachew, S Berthet, C Kaldis, P Gallo, V AF Jablonska, Beata Aguirre, Adan Vandenbosch, Renaud Belachew, Shibeshih Berthet, Cyril Kaldis, Philipp Gallo, Vittorio TI Cdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ROSTRAL MIGRATORY STREAM; CYCLIN-DEPENDENT KINASES; OLIGODENDROCYTE PROGENITORS; NG2-EXPRESSING CELLS; DNA-REPLICATION; NERVOUS-SYSTEM; OLFACTORY-BULB; IN-VIVO; S-PHASE; NEUROGENESIS AB We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)-expressing progenitor cells of the subventricular zone (SVZ) show no significant difference in density and proliferation between Cdk2(-/-) and wild-type mice at perinatal ages and are reduced only in adult Cdk2(-/-) mice. Adult Cdk2(-/-) SVZ cells in culture display decreased self-renewal capacity and enhanced differentiation. Compensatory mechanisms in perinatal Cdk2(-/-) SVZ cells, which persist until postnatal day 15, involve increased Cdk4 expression that results in retinoblastoma protein inactivation. A subsequent decline in Cdk4 activity to wild-type levels in postnatal day 28 Cdk2(-/-) cells coincides with lower NG2(+) proliferation and self-renewal capacity similar to adult levels. Cdk4 silencing in perinatal Cdk2(-/-) SVZ cells abolishes Cdk4 up-regulation and reduces cell proliferation and self-renewal to adult levels. Conversely, Cdk4 overexpression in adult SVZ cells restores proliferative capacity to wildtype levels. Thus, although Cdk2 is functionally redundant in perinatal SVZ, it is important for adult progenitor cell proliferation and self-renewal through age-dependent regulation of Cdk4. C1 [Jablonska, Beata; Aguirre, Adan; Gallo, Vittorio] Childrens Natl Med Ctr, Neurosci Res Ctr, Washington, DC 20010 USA. [Vandenbosch, Renaud; Belachew, Shibeshih] Univ Liege, Ctr Cellular & Mol Neurobiol, Dept Neurol, B-4000 Liege, Belgium. [Berthet, Cyril; Kaldis, Philipp] Natl Canc Inst, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Gallo, V (reprint author), Childrens Natl Med Ctr, Neurosci Res Ctr, Washington, DC 20010 USA. EM vgallo@cnmcresearch.org RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU NICHD NIH HHS [P30 HD040677, P30HD40677]; NINDS NIH HHS [R01 NS045702, R01NS045702] NR 53 TC 51 Z9 56 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 17 PY 2007 VL 179 IS 6 BP 1231 EP 1245 DI 10.1083/jcb.200702031 PG 15 WC Cell Biology SC Cell Biology GA 242AQ UT WOS:000251697300016 PM 18086919 ER PT J AU Jin, H Manetz, S Leininger, J Luke, C Subbarao, K Murphy, B Kemble, G Coelingh, KL AF Jin, H. Manetz, S. Leininger, J. Luke, C. Subbarao, K. Murphy, B. Kemble, G. Coelingh, K. L. TI Toxicological evaluation of live attenuated, cold-adapted H5N1 vaccines in ferrets SO VACCINE LA English DT Article DE influenza; vaccine; H5N1; toxicology; ferrets ID INFLUENZA-VIRUS VACCINE; A VIRUS; TRIVALENT; CHILDREN; INTRANASAL; PROTECTION; EFFICACY; VOLUNTEERS; MICE AB Live attenuated influenza vaccines (LAIV) have several attributes related to safety, immunogenicity, cross-protection against antigenic drift strains, high yield and needle-free administration that make them attractive candidates for control of pandemic influenza. H5N1 LAIV vaccine candidates are attenuated in ferrets, chickens and mice. These vaccine candidates were further characterized in the ferret model to evaluate their toxicity at doses comparable to seasonal LAIV and at doses up to 100-fold higher. The results demonstrated that H5N1 LAIV, even when administered at high doses, is restricted in replication in the lower respiratory tract of ferrets. However, intranasal administration of 0.5 mL can result in deposition of H5N1 LAIV in the ferret lung, where it induces a pulmonary inflammatory response in the absence of significant local replication of the vaccine virus. Thus, smaller vaccine dose volumes should be considered for evaluation of LAIV in animal models. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Jin, H.; Kemble, G.] Medimmune Inc, Mountain View, CA 94043 USA. [Manetz, S.; Leininger, J.; Coelingh, K. L.] Medimmune Inc, Gaithersburg, MD 20878 USA. [Luke, C.; Subbarao, K.; Murphy, B.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Jin, H (reprint author), Medimmune Inc, 297 N Bernardo Ave, Mountain View, CA 94043 USA. EM jinh@medimmune.com FU Intramural NIH HHS NR 23 TC 21 Z9 23 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 17 PY 2007 VL 25 IS 52 BP 8664 EP 8672 DI 10.1016/j.vaccine.2007.10.032 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 253DC UT WOS:000252497900004 PM 18031873 ER PT J AU Zaharoff, DA Rogers, CJ Hance, KW Schlom, J Greiner, JW AF Zaharoff, David A. Rogers, Connie J. Hance, Kenneth W. Schlom, Jeffrey Greiner, John W. TI Chitosan solution enhances the immunoadjuvant properties of GM-CSF SO VACCINE LA English DT Article DE chitosan; immunoadjuvant; GM-CSF; controlled release; cytokine ID COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; SYSTEMIC ANTITUMOR IMMUNITY; REGIONAL LYMPH-NODES; FACTOR RHGM-CSF; CONTROLLED-RELEASE; INTERFERON-GAMMA; LOCAL-DELIVERY; INTRANASAL IMMUNIZATION; LOADED MICROSPHERES AB Sustained, local delivery of immunomodulatory cytokines is under investigation for its ability to enhance vaccine and anti-tumor responses both clinically and preclinically. This study evaluates the ability of chitosan, a biocompatible polysaccharicle, to (1) control the dissemination of a cytokine, GM-CSF, and (2) enhance the immunoadjuvant properties of GM-CSF. While cytokines have previously been delivered in lipid-based adjuvants and other vehicles, these do not have the clinical safety profile or unique properties of chitosan. We found that chitosan solution maintained a measurable depot of recombinant GM-CSF (rGM-CSF) at a subcutaneous injection site for up to 9 days. In contrast, when delivered in a saline vehicle, rGM-CSF was undetectable in 12-24 h. Furthermore, a single s.c. injection of 20 mu g rGM-CSF in chitosan solution (chitosan/rGM-CSF(20 mu g)) transiently expanded lymph nodes up to 4.6-fold and increased the number of MHC class II expressing cells and dendritic cells by 7.4-fold and 6.8-fold, respectively. These increases were significantly greater than those measured when rGM-CSF was administered in saline at the standard preclinical dose and schedule, i.e. 4 daily s.c. injections of 20 mu g. Furthermore, lymph node cells from mice injected with chitosan/rGM-CSF(20 mu g) induced greater allogeneic T cell proliferation, indicating enhanced antigen presenting capability, than lymph node cells from mice injected with rGM-CSF alone. Finally, in vaccination experiments, chitosan/rGM-CSF was superior to either chitosan or rGM-CSF alone in enhancing the induction of antigen-specific CD4(+) proliferation, peptide-specific CD8(+) pentamer staining and cytotoxic T cell lysis. Altogether, chitosan/rGM-CSF outperformed standard rGM-CSF administrations in dendritic cell recruitment, antigen presentation and vaccine enhancement. We conclude that chitosan solution is a promising delivery platform for the sustained, local delivery of rGM-CSF. Published by Elsevier Ltd. C1 [Zaharoff, David A.; Rogers, Connie J.; Hance, Kenneth W.; Schlom, Jeffrey; Greiner, John W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Greiner, JW (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Center Dr,Room 8B09, Bethesda, MD 20892 USA. EM jg117s@nih.gov OI Zaharoff, David/0000-0001-6885-6727 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010598-04] NR 57 TC 32 Z9 35 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 17 PY 2007 VL 25 IS 52 BP 8673 EP 8686 DI 10.1016/j.vaccine.2007.10.037 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 253DC UT WOS:000252497900005 PM 18037196 ER PT J AU Sapp, JC Turner, JT van de Kamp, JM van Dijk, FS Lowry, RB Biesecker, LG AF Sapp, Julie C. Turner, Joyce T. van de Kamp, Jiddeke M. van Dijk, Fleur S. Lowry, R. Brian Biesecker, Leslie G. TI Newly delineated syndrome of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome) in seven patients SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article; Proceedings Paper CT Festschrift Symposium 2007 held in Honor of M Michael Cohen CY MAR 31, 2007 CL Univ Utah, Salt Lake City, UT HO Univ Utah DE overgrowth; asymmetric overgrowth; hemihyperplasia; bone distortion; Proteus syndrome; hemihyperplasia-multiple lipomatosis syndrome (HHML); Klippel-Trenaunay syndrome ID PROTEUS-SYNDROME; DIAGNOSTIC-CRITERIA; CHALLENGES AB We present a series of seven patients who were previously diagnosed with Proteus syndrome, but who do not meet published diagnostic criteria for this disorder and whose natural history is distinct from that of Proteus syndrome. This newly recognized phenotype comprises progressive, complex, and mixed truncal vascular malformations, dysregulated adipose tissue, varying degrees of scoliosis, and enlarged bony structures without progressive bony overgrowth. We have named this condition congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome) on a heuristic basis. in contrast to the bony distortion so characteristic of Proteus syndrome, distortion in CLOVE syndrome occurs only following major or radical surgery. Here, we contrast differences and similarities of CLOVE syndrome to Proteus syndrome. (C) 2007 Wiley-Liss, Inc. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, VU Univ Med Ctr, Amsterdam, Netherlands. Univ Calgary, Dept Med Genet, Calgary, AB, Canada. Alberta Childrens Prov Gen Hosp, Calgary, AB T2T 5C7, Canada. RP Biesecker, LG (reprint author), Bldg 49,Room 4A80, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov FU Intramural NIH HHS NR 11 TC 84 Z9 86 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 15 PY 2007 VL 143A IS 24 BP 2944 EP 2958 DI 10.1002/ajmg.a.32023 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 237VS UT WOS:000251405100015 PM 17963221 ER PT J AU Doherty, ES Lacbawan, F Hadley, DW Brewer, C Zalewski, C Kim, HJ Solomon, B Rosenbaum, K Domingo, DL Hart, TC Brooks, BP Immken, L Lowry, RB Kimonis, V Shanske, AL Jehee, FS Bueno, MRP Knightly, C McDonald-McGinn, D Zackai, EH Muenke, M AF Doherty, Emily S. Lacbawan, Felicitas Hadley, Donald W. Brewer, Carmen Zalewski, Christopher Kim, H. Jeff Solomon, Beth Rosenbaum, Kenneth Domingo, Demetrio L. Hart, Thomas C. Brooks, Brian P. Immken, LaDonna Lowry, R. Brian Kimonis, Virginia Shanske, Alan L. Jehee, Fernanda Sarquis Bueno, Maria Rita Passos Knightly, Carol McDonald-McGinn, Donna Zackai, Elaine H. Muenke, Maximilian TI Muenke syndrome (FGFR3-related craniosynostosis): Expansion of the phenotype and review of the literature SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article; Proceedings Paper CT Festschrift Symposium 2007 held in Honor of M Michael Cohen CY MAR 31, 2007 CL Univ Utah, Salt Lake City, UT HO Univ Utah DE craniosynostosis; Muenke syndrome; fibroblastgrowth factor receptor 3; coronal suture synostosis; hearing loss; developmental delay; speech delay ID FIBROBLAST-GROWTH-FACTOR; SAETHRE-CHOTZEN-SYNDROME; UNILATERAL CORONAL SYNOSTOSIS; SENSORINEURAL HEARING-LOSS; FACTOR RECEPTOR-3 GENE; UNIQUE POINT MUTATION; PRO250ARG MUTATION; MISSENSE MUTATION; FGFR3 MUTATION; P250R AB Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. Reduced penetrance and variable expressivity contribute to the wide spectrum of clinical findings in Muenke syndrome. To better define the clinical features of this syndrome, we initiated a study of the natural history of Muenke syndrome. To date, we have conducted a standardized evaluation of nine patients with a confirmed Pro250Arg mutation in FGFR3. We reviewed audiograms from an additional 13 patients with Muenke syndrome. A majority of the patients (95%) demonstrated a mild-to-moderate, low frequency sensorineural hearing loss. This pattern of heating loss was not previously recognized as characteristic of Muenke syndrome. We also report on feeding and swallowing difficulties in children with Muenke syndrome. Combining 312 reported cases of Muenke syndrome with data from the nine NIH patients, we found that females with the Pro250Arg mutation were significantly more likely to be reported with craniosynostosis than males (P<0.01). Based on our findings, we propose that the clinical management should include audiometric and developmental assessment in addition to standard clinical care and appropriate genetic Counseling. Published 2007 Wiley-Liss, Inc.dagger. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NEI, NIH, Bethesda, MD 20892 USA. Specially Children, Austin, TX USA. Alberta Childrens Prov Gen Hosp, Dept Med Genet, Calgary, AB T2T 5C7, Canada. Univ Calgary, Calgary, AB, Canada. Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp Montefiore, Bronx, NY USA. Univ Sao Paulo, Sao Paulo, Brazil. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Caril Clin, Roanoke, VA USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,Rm 1B203,MSC 3717, Bethesda, MD 20892 USA. EM muenke@nih.gov FU Intramural NIH HHS NR 50 TC 54 Z9 54 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 15 PY 2007 VL 143A IS 24 BP 3204 EP 3215 DI 10.1002/ajmg.a.32078 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 237VS UT WOS:000251405100043 PM 18000976 ER PT J AU Kimani, JW Shi, M Daack-Hirsch, S Christensen, K Moretti-Ferreira, D Marazita, ML Field, LL Canady, JW Murray, JC AF Kimani, Jane W. Shi, Min Daack-Hirsch, Sandra Christensen, Kaare Moretti-Ferreira, Danilo Marazita, Mary L. Field, L. Leigh Canady, John W. Murray, Jeffrey C. TI X-chromosome inactivation patterns in monozygotic twins and sib pairs discordant for nonsyndromic cleft lip and/or palate SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article; Proceedings Paper CT Festschrift Symposium 2007 held in Honor of M Michael Cohen CY MAR 31, 2007 CL Univ Utah, Salt Lake City, UT HO Univ Utah DE cleft palate; cleft lip; X inactivation; monozygotic twins; discordant ID PHENOTYPIC DISCORDANCE; GENOME SCAN; MZ TWINS; MUTATIONS; MSX1; DISEASE; HUMANS; LOCI AB Nonsyndromic clefts of the lip and/or palate are common birth defects with a strong genetic component. Based on unequal gender ratios for clefting phenotypes, evidence for linkage to the X chromosome and the occurrence of several X-linked clefting syndromes, we investigated the role of skewed X chromosome inactivation (XCI) in orofacial clefts. Our samples consisted of female monozygotic (MZ) twins (n = 8) and sister pairs (n = 152) discordant for nonsyndromic clefting. We measured the XCI pattern in peripheral blood lymphocyte DNA using a methylation based androgen receptor gene assay. Skewing of XCI was defined as the deviation in inactivation pattern from a 50:50 ratio. Our analysis revealed no significant difference in the degree of skewing between twin pairs (P = 0.3). However, borderline significant differences were observed in the sister pairs (P = 0.02), with the cleft lip with cleft palate group showing the most significant result (P=0.01). We did not find evidence for involvement of skewed XCI in the discordance for clefting in our sample of female MZ twins. However, results from the paired sister study suggest the potential contribution of skewed XCI to orofacial clefting, particularly cleft lip and palate. (C) 2007 Wiley-Liss, Inc. C1 Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ So Denmark, Dept Epidemiol, Odense, Denmark. Genet Univ Estadual Paulista, Serv Aconselhamento, Botucatu, SP, Brazil. Univ Pittsburgh, Dept Oral Biol, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. Univ Iowa, Dept Otolaryngol Plast Surg & Orthopedic Surg, Iowa City, IA USA. RP Murray, JC (reprint author), Univ Iowa, Dept Pediat, 2182 Med Labs, Iowa City, IA 52242 USA. EM jeff-murray@uiowa.edu RI Christensen, Kaare/C-2360-2009; Moretti-Ferreira, Danilo/F-9565-2012; OI Christensen, Kaare/0000-0002-5429-5292; Moretti-Ferreira, Danilo/0000-0002-9256-7623 FU Intramural NIH HHS [Z99 ES999999]; NIDCR NIH HHS [R01 DE011948, K02 DE015291, K02 DE015291-01, K02 DE015291-02, K02 DE015291-03, K02 DE015291-04, K02 DE015291-05, P50 DE016215, P50 DE016215-04, P50-DE016215, P60 DE013076, P60 DE013076-010005, P60 DE013076-01S10005, P60 DE013076-020005, P60 DE013076-030005, P60 DE013076-03S10005, P60 DE013076-040005, P60 DE013076-050005, R01 DE009886, R01 DE014667, R01 DE014667-01, R01 DE014667-02, R01 DE014667-03, R01 DE014667-04, R01 DE014667-05, R01 DE014667-06, R01 DE014667-07, R01 DE014667-08, R01 DE015197, R01 DE015197-04, R01 DE016148, R01-DE-015197, R01-DE-09886, R01-DE011948, R01-DE014667, R01-DE016148, R21 DE016930, R21-DE016930, R37 DE008559, R37 DE008559-18, R37-DE-08559] NR 33 TC 11 Z9 12 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 15 PY 2007 VL 143A IS 24 BP 3267 EP 3272 DI 10.1002/ajmg.a.32098 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 237VS UT WOS:000251405100049 PM 18000982 ER PT J AU Nabel, EG AF Nabel, Elizabeth G. TI Notes from the NHLBI director: Shaping the future of research - The NHLBI strategic plan SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 [Nabel, Elizabeth G.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 15 PY 2007 VL 176 IS 12 BP 1178 EP 1178 DI 10.1164/rccm.200709-1382ED PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 243PZ UT WOS:000251811100003 PM 18057424 ER PT J AU Nguyen, KT Wu, JC Boylan, JA Gherardini, FC Pei, D AF Nguyen, Kiet T. Wu, Jen-Chieh Boylan, Julie A. Gherardini, Frank C. Pei, Dehua TI Zinc is the metal cofactor of Borrelia burgdorferi peptide deformylase SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE peptide deformylase; hydrolase; iron; zinc; metal specificity; catalysis ID ATOMIC-ABSORPTION-SPECTROMETRY; BACTERIUM LEPTOSPIRA-INTERROGANS; ACTIVE-SITE METAL; ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; METHIONINE AMINOPEPTIDASE; SPECTROPHOTOMETRIC ASSAY; CRYSTAL-STRUCTURE; PROTEIN; IRON AB Peptide deformylase (PDF, E.C. 3.5.1.88) catalyzes the removal of N-terminal formyl groups from nascent ribosome-synthesized polypeptides. PDF contains a catalytically essential divalent metal ion, which is tetrahedrally coordinated by three protein ligands (His, His, and Cys) and a water molecule. Previous studies revealed that the metal cofactor is a Fe2+ ion in Escherichia coli and many other bacterial PDFs. In this work, we found that PDFs from two iron-deficient bacteria, Borrelia burgdorferi and Lactobacillus plantarum, are stable and highly active under aerobic conditions. The native B. burgdoiferi PDF (BbPDF) was purified 1200-fold and metal analysis revealed that it contains similar to 1.1 Zn2+ ion/polypeptide but no iron. Our studies suggest that PDF utilizes different metal ions in different organisms. These data have important implications in designing PDF inhibitors and should help address some of the unresolved issues regarding PDF structure and catalytic function. (c) 2007 Elsevier Inc. All rights reserved. C1 Ohio State Univ, Dept Chem, Ohio State Biochem Program, Columbus, OH 43210 USA. NIAID, Rocky Mt Lab, Lab Zoon Pathogens, Hamilton, MT 59840 USA. RP Pei, D (reprint author), Ohio State Univ, Dept Chem, Ohio State Biochem Program, 100 W 18th Ave, Columbus, OH 43210 USA. EM pei.3@osu.edu FU NIAID NIH HHS [AI62901, R01 AI040575-09, R01 AI062901-03, R01 AI062901, AI40575, R01 AI040575] NR 62 TC 25 Z9 25 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC 15 PY 2007 VL 468 IS 2 BP 217 EP 225 DI 10.1016/j.abb.2007.09.023 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 238TA UT WOS:000251469300008 PM 17977509 ER PT J AU Brehm, MA Schenk, TMH Zhou, X Fanick, W Lin, H Windhorst, S Nalaskowski, MM Kobras, M Shears, SB Mayr, GW AF Brehm, Maria A. Schenk, Tobias M. H. Zhou, Xuefei Fanick, Werner Lin, Hongying Windhorst, Sabine Nalaskowski, Marcus M. Kobras, Mario Shears, Stephen B. Mayr, Georg W. TI Intracellular localization of human Ins(1,3,4,5,6)P-5 2-kinase SO BIOCHEMICAL JOURNAL LA English DT Article DE euchromatin; Ins(1,3,4,5,6)P-5 2-kinase (IP5K); in situ hybridization; nuclear localization; stress granule ID INOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE 2-KINASE; MESSENGER-RNA; NUCLEAR-LOCALIZATION; STRESS GRANULES; MYOINOSITOL HEXAKISPHOSPHATE; EXPORT; CELLS; 1,4,5-TRISPHOSPHATE; POLYPHOSPHATES; KINASES AB InSP6 is an intracellular signal with several proposed functions that is synthesized by IP5K [Ins(1,3,4,5,6)P-5 2-kinase]. In the present study, we overexpressed EGFP (enhanced green fluorescent protein)-IP5K fusion proteins in NRK (normal rat kidney), COS7 and H1299 cells. The results indicate that there is spatial microheterogeneity in the intracellular localization of IP5K that could also be confirmed for the endogenous enzyme. This may facilitate changes in InSP6 levels at its sites of action. For example, overexpressed IP5K showed a structured organization within the nucleus. The kinase was preferentially localized in euchromatin and nucleoli, and co-localized with mRNA. In the cytoplasm, the overexpressed IP5K showed locally high concentrations in discrete foci. The latter were attributed to stress granules by using mRNA, PABP [poly(A)-binding protein] and TIAR (TIA-1-related protein) as markers. The incidence of stress granules, in which IP5K remained highly concentrated, was further increased by puromycin treatment. Using FRAP (fluorescence recovery after photobleaching) we established that IP5K was actively transported into the nucleus. By site-directed mutagenesis we identified a nuclear import signal and a peptide segment mediating the nuclear export of IP5K. C1 [Brehm, Maria A.; Shears, Stephen B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Schenk, Tobias M. H.; Zhou, Xuefei; Fanick, Werner; Lin, Hongying; Windhorst, Sabine; Nalaskowski, Marcus M.; Kobras, Mario; Mayr, Georg W.] Univ Klinikum Hamburg Eppendorf, Inst Med Biochem & Mol Biol 1, D-20246 Hamburg, Germany. RP Shears, SB (reprint author), NIEHS, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov; mayr@uke.uni-hamburg.de NR 55 TC 24 Z9 27 U1 1 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 15 PY 2007 VL 408 BP 335 EP 345 DI 10.1042/BJ20070382 PN 3 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244SA UT WOS:000251884400004 PM 17705785 ER PT J AU Insel, TR AF Insel, Thomas R. TI From animal models to model animals SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID BEHAVIOR; BRAIN C1 NIMH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, 6001 Execut Blvd,Room 8235,MSC 9669, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov NR 22 TC 48 Z9 50 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2007 VL 62 IS 12 BP 1337 EP 1339 DI 10.1016/j.biopsych.2007.10.001 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 239CQ UT WOS:000251496400001 PM 18054535 ER PT J AU Ghosh, AK Dawson, ZL Mitsuya, H AF Ghosh, Arun K. Dawson, Zachary L. Mitsuya, Hiroaki TI Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE protease inhibitors; darunavir; design and synthesis ID VIRUS TYPE-1 PROTEASE; CRYSTAL-STRUCTURE; IN-VITRO; POTENT; THERAPY; PI; SAQUINAVIR; INFECTION; DISCOVERY; SELECTION AB Our structure-based design strategies which specifi. cally target the HIV-1 protease backbone, resulted in a number of exceedingly potent nonpeptidyl inhibitors. One of these inhibitors, darunavir (TMC114), contains a privileged, structure-based designed high-affinity P2 ligand, 3(R), 3a(S), 6a(R) bis-tetrahydrofuranylurethane (bis-THF). Darunavir has recently been approved for the treatment of HIV/AIDS patients harboring multidrug-resistant HIV-1 variants that do not respond to previously existing HAART regimens. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Ghosh, Arun K.; Dawson, Zachary L.] Purdue Univ, Dept Chem & Med Chem, W Lafayette, IN 47907 USA. [Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol & Infect Dis, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem & Med Chem, W Lafayette, IN 47907 USA. EM akghosh@purdue.edu FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM053386, GM 53386, R01 GM053386-12, R37 GM053386] NR 31 TC 86 Z9 87 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD DEC 15 PY 2007 VL 15 IS 24 BP 7576 EP 7580 DI 10.1016/j.bmc.2007.09.010 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 267DH UT WOS:000253489200008 PM 17900913 ER PT J AU Nabel, EG AF Nabel, Elizabeth G. TI Shaping the future of research: The NHLBI strategic plan SO BLOOD LA English DT Editorial Material C1 NHLBI, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2007 VL 110 IS 13 BP 4143 EP 4143 DI 10.1182/blood-2007-09-113621 PG 1 WC Hematology SC Hematology GA 246IR UT WOS:000252001200009 PM 18056844 ER PT J AU Little, RF Aleman, K Kumar, P Wyvill, KM Pluda, JM Read-Connole, E Wang, V Pittaluga, S Catanzaro, AT Steinberg, SM Yarchoan, R AF Little, Richard F. Aleman, Karen Kumar, Pallavi Wyvill, Kathleen M. Pluda, James M. Read-Connole, Elizabeth Wang, Victoria Pittaluga, Stefania Catanzaro, Andrew T. Steinberg, Seth M. Yarchoan, Robert TI Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin-12 for AIDS-related Kaposi sarcoma SO BLOOD LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; PROTEIN-COUPLED RECEPTOR; ENDOTHELIAL GROWTH-FACTOR; NON-HODGKINS-LYMPHOMA; INTERFERON-GAMMA; CLINICAL-TRIALS; IFN-GAMMA; CELL LUNG; ANGIOGENESIS; HERPESVIRUS AB Thirty-six patients with AIDS-associated Kaposi sarcoma (KS) requiring chemotherapy were treated for six 3-week cycles of pegylated liposomal doxorubicin (20 mg/m(2)) plus interieukin-12 (IL-12; 300 ng/kg subcutaneously twice weekly), followed by 500 ng/kg subcutaneous IL-12 twice weekly for up to 3 years. All received highly active antiretroviral therapy (HAART). Twenty-two had poor-prognosis KS (T1S1). Thirty patients had a major response, including 9 with complete response, yielding an 83.3% major response rate (95% confidence interval: 67.2%-93.6%). Median time to first response was 2 cycles. Median progression was not reached at median potential follow-up of 46.9 months. Of 27 patients with residual disease when starting maintenance IL-12, 15 had a new major response compared with this new baseline. The regimen was overall well tolerated; principal toxicities were neutropenia, anemia, transaminitis, and neuropsychiatric toxicity. Patients had increases in serum IL-12, interferon gamma, and inducible protein-10 (IP-10), and these remained increased at weeks 18 and 34. The regimen of IL-12 plus liposomal doxorubicin yielded rapid tumor responses and a high response rate in patients with AIDS-KS receiving HAART, and responses were sustained on IL-12 maintenance therapy. A randomized trial of IL-12 in this setting may be warranted. This study is registered at http://www.clinicaltrials.gov as no. NCT00020449. C1 [Little, Richard F.; Aleman, Karen; Kumar, Pallavi; Wyvill, Kathleen M.; Pluda, James M.; Read-Connole, Elizabeth; Wang, Victoria; Catanzaro, Andrew T.; Yarchoan, Robert] NCI, Ctr Canc Res, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Ctr Canc Res, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), Bldg 10,Rm 10N106,MSC 1868 NIH, Bethesda, MD 20892 USA. EM yarchoan@helix.nih.gov FU Intramural NIH HHS NR 51 TC 16 Z9 18 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2007 VL 110 IS 13 BP 4165 EP 4171 DI 10.1182/blood-2007-06-097568 PG 7 WC Hematology SC Hematology GA 246IR UT WOS:000252001200014 PM 17846226 ER PT J AU Wang, LH Yang, XY Zhang, XH Farrar, WL AF Wang, Li Hua Yang, Xiao Yi Zhang, Xiaohu Farrar, William L. TI Inhibition of adhesive interaction between multiple myeloma and bone marrow stromal cells by PPAR gamma cross talk with NF-kappa B and C/EBP beta SO BLOOD LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; SOLUBLE INTERLEUKIN-6 RECEPTOR; ENDOTHELIAL GROWTH-FACTOR; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); GLUCOCORTICOID-RECEPTOR; SIGNALING PATHWAY; FACTORS NF-IL6; C-JUN; EXPRESSION; MOLECULES AB Binding of multiple myeloma (MM) cells to bone marrow stromal cells (BMSCs) triggers expression of adhesive molecules and secretion of interleukin-6 (IL-6), promoting MM cell growth, survival, drug resistance, and migration, which highlights the possibility of developing and validating novel anti-MM therapeutic strategies targeting MM cells-host BMSC interactions and their sequelae. Recently, we have found that expression of the peroxisome proliferator-activated receptor gamma (PPAR gamma) and its ligands can potently inhibit IL-6-regulated MM cell growth. Here we demonstrate that PPAR gamma agonists 15-d-PGJ2 and troglitazone significantly suppress cell-cell adhesive events, including expression of adhesion molecules and IL-6 secretion from BMSCs triggered by adhesion of MM cells, as well as overcome drug resistance by a PPAR gamma-dependent mechanism. The synthetic and natural PPAR gamma agonists have diverging and overlapping mechanisms blocking transactivation of transcription factors NF-kappa B and 5'-CCAAT/enhancer-binding protein beta (C/EBP beta). Both 15-d-PGJ2 and troglilazone blocked C/EBP beta transcriptional activity by forming PPAR gamma complexes with C/EBP beta. 15-d-PGJ2 and trogiltazone also blocked NF-kappa B activation by recruiting the coactivator PGC-1 from p65/ p50 complexes. In addition, 15-d-PGJ2 had a non-PPAR gamma-dependent effect by inactivation of phosphorylation of IKK and I kappa B. These studies provide the framework for PPAR gamma-based pharmacological strategies targeting adhesive interactions of MM cells with the bone marrow microenvironment. C1 [Wang, Li Hua; Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Frederick, MD 21701 USA. [Wang, Li Hua; Yang, Xiao Yi; Zhang, Xiaohu] NCI, NIH, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. RP Wang, LH (reprint author), NCI, NIH, Basic Res Program, SAIC Frederick, POB B, Frederick, MD 21702 USA. EM lhwang@ncifcrf.gov; faffar@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01 CO12400] NR 56 TC 38 Z9 42 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2007 VL 110 IS 13 BP 4373 EP 4384 DI 10.1182/blood-2006-07-038026 PG 12 WC Hematology SC Hematology GA 246IR UT WOS:000252001200044 PM 17785586 ER PT J AU Young, KH Weisenburger, DD Dave, BJ Smith, L Sanger, W Iqbal, J Campo, E Delabie, J Gascoyne, RD Ott, G Rimsza, L Mueller-Hermelink, HK Jaffe, ES Rosenwald, A Staudt, LM Chan, WC Greiner, TC AF Young, Ken H. Weisenburger, Dennis D. Dave, Bhavana J. Smith, Lynette Sanger, Warren Iqbal, Javeed Campo, Elias Delabie, Jan Gascoyne, Randy D. Ott, German Rimsza, Lisa Mueller-Hermelink, H. Konrad Jaffe, Elaine S. Rosenwald, Andreas Staudt, Louis M. Chan, Wing C. Greiner, Timothy C. TI Mutations in the DNA-binding codons of TP53, which are associated with decreased expression of TRAIL receptor-2, predict for poor survival in diffuse large B-cell lymphoma SO BLOOD LA English DT Article ID P53 GENE-MUTATIONS; NON-HODGKINS-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; CHEMOTHERAPY PLUS RITUXIMAB; TUMOR-SUPPRESSOR GENE; QUANTITATIVE PCR; DEATH RECEPTORS; CANCER-CELLS; PROGNOSIS; APOPTOSIS AB Mutations of the TP53 tumor suppressor gene have been associated with poor survival in some series of diffuse large B-cell lymphoma (DLBCL) but not in other studies. The purpose of this study was to identify the frequency of TP53 alterations (mutations or deletions), characterize the gene expression of mutant/deleted cases, and determine the effects of mutations on survival. In a series of DLBCL that had previous gene expression profiling, we identified 24 mutations in 113 cases (21%). There was no difference in the frequency of mutations in the molecular subgroups of DLBCL. Twelve (50%) of the 24 cases had mutations localized to the DNA-binding codons in the core domain of TP53. The presence of any TP53 mutation correlated with poor overall survival (OS; P =.044), but DNA-binding mutations were the most significant predictor of poor OS (P <.001). Multivariate, analysis confirmed that the International Prognostic Index, tumor size, and TP53 DNA-binding mutations were independent predictors of OS. Gene expression analysis showed that TRAIL receptor-2 (DR5) was the most differentially underexpressed gene in the TP53 mutated cases. Investigation is warranted into targeted therapy toward TRAIL receptor-2, to potentially bypass the adverse effect of mutated TP53 in DLBCL. C1 [Young, Ken H.; Weisenburger, Dennis D.; Iqbal, Javeed; Chan, Wing C.; Greiner, Timothy C.] Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. [Dave, Bhavana J.; Sanger, Warren] Univ Nebraska, Med Ctr, Human Genet Lab, Munroe Meyer Inst Genet & Rehabil, Omaha, NE 68198 USA. [Smith, Lynette] Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE 68198 USA. [Campo, Elias] Univ Barcelona, Barcelona, Spain. [Delabie, Jan] Norwegian Radium Hosp, Oslo, Norway. [Delabie, Jan] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Ott, German; Mueller-Hermelink, H. Konrad; Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. [Rimsza, Lisa] Univ Arizona, Dept Pathol, Tucson, AZ USA. [Jaffe, Elaine S.] NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. [Staudt, Louis M.] NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. RP Greiner, TC (reprint author), Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, 983135 Nebraska Med Ctr, Omaha, NE 68198 USA. EM tgreiner@unmc.edu RI TOMBLIN, Bruce/I-2257-2012; OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 FU Intramural NIH HHS; NCI NIH HHS [CA36727, CA84967, P30 CA036727, U01 CA084967] NR 65 TC 47 Z9 50 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2007 VL 110 IS 13 BP 4396 EP 4405 DI 10.1182/blood-2007-02-072082 PG 10 WC Hematology SC Hematology GA 246IR UT WOS:000252001200046 PM 17881637 ER PT J AU Morton, LM Landgren, O Chatterjee, N Castenson, D Parsons, R Hoover, RN Engels, EA AF Morton, Lindsay M. Landgren, Ola Chatterjee, Nilanjan Castenson, David Parsons, Ruth Hoover, Robert N. Engels, Eric A. TI Hepatitis C virus infection and risk of posttransplantation lymphoproliferative disorder among solid organ transplant recipients SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS; LIVER-TRANSPLANTATION; HCV INFECTION; UNITED-STATES; B-CELLS; AIDS; IMMUNOSUPPRESSION; TRENDS; METAANALYSIS AB Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Hepatitis C virus (HCV) infection has been linked to increased risk of lymphoma among immunocompetent individuals. We therefore investigated the association between HCV infection and PTLD in a retrospective cohort study of all individuals in the United States who received their first solid organ transplant from 1994 to 2005 (N = 210 763) using Scientific Registry of Transplant Recipients data. During followup, 1630 patients with PTLD were diagnosed. HCV prevalence at transplantation was 11.3%. HCV infection did not increase PTLD risk in the total cohort (Cox regression model, hazard ratio [HR] = 0.84; 95% confidence interval [Cl] 0.68-1.05), even after adjustment for type of organ transplanted, indication for transplantation, degree of HLA mismatch, donor type, or use of immunosuppression medications. Additional analyses also revealed no association by PTLD subtype (defined by site, pathology, cell type, and tumor Epstein-Barr virus [EBV] status). HCV infection did increase PTLD risk among the 2.8% of patients (N = 5959) who were not reported to have received immunosuppression maintenance medications prior to hospital discharge (HR = 3.09; 95% Cl, 1.14-8.42; P interaction = .007). Our findings suggest that HCV is not a major risk factor for PTLD, which is consistent with the model in which an intact immune system is necessary for development of HCV-related lymphoproliferation. C1 [Morton, Lindsay M.; Landgren, Ola; Chatterjee, Nilanjan; Hoover, Robert N.; Engels, Eric A.] NIH, Natl Canc Inst, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Rockville, MD USA. [Castenson, David; Parsons, Ruth] Informat Management Serv Inc, Rockville, MD USA. RP Morton, LM (reprint author), NIH, Natl Canc Inst, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Rockville, MD USA. RI Morton, Lindsay/B-5234-2015 OI Morton, Lindsay/0000-0001-9767-2310 FU Intramural NIH HHS; PHS HHS [231-00-0116] NR 43 TC 23 Z9 26 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2007 VL 110 IS 13 BP 4599 EP 4605 DI 10.1182/blood-2007-07-101956 PG 7 WC Hematology SC Hematology GA 246IR UT WOS:000252001200069 PM 17855632 ER PT J AU Yang, Q Zhang, R Horikawa, I Fujita, K Afshar, Y Kokko, A Laiho, P Aaltonen, LA Harris, CC AF Yang, Qin Zhang, Ran Horikawa, Izumi Fujita, Kaori Afshar, Yalda Kokko, Antti Laiho, Paivi Aaltonen, Lauri A. Harris, Curtis C. TI Functional diversity of human protection of telomeres 1 isoforms in telomere protection and cellular senescence SO CANCER RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; ABERRANT HOMOLOGOUS RECOMBINATION; NONPOLYPOSIS COLORECTAL-CANCER; DNA-DAMAGE CHECKPOINT; HUMAN-CELLS; MISMATCH REPAIR; G-QUADRUPLEXES; TUMOR-CELLS; IN-VITRO; POT1 AB Protection of telomeres 1 (POT1) proteins in various organisms bind telomeres and regulate their structure and function. In contrast to mice carrying two distinct POT1 genes encoding two POT1 proteins (POT1a and POT1b), humans have the single POT1 gene. In addition to full-length POT1 protein (variant v1), the human POT1 gene encodes four other variants due to alternative RNA splicing (variants v2, v3, v4, and v5), whose functions are poorly understood. The functional analyses of the NH2-terminally and COOH-terminally truncated POT1 variants in this study showed that neither the single-stranded telomere-binding ability of the NH2-terminal oligonucleotide-binding (OB) folds nor the telomerase dependent telomere elongation activity mediated by the COOH-terminal TPPI-interacting domain was telomere protective by itself. Importantly, a COOH-terminally truncated variant (v5), which consists of the NH2-terminal OB folds and the central region of unknown function, was found to protect telomeres and prevent cellular senescence as efficiently as v1. Our data revealed mechanistic and functional differences between vi and v5: (a) v1, but not v5, functions through the maintenance of telomeric 3 ' overhangs; (b) p53 is indispensable to v5 knockdown-induced senescence; and (c) v5 functions at only a fraction of telomeres to prevent DNA damage signaling. Furthermore, v5 was preferentially expressed in mismatch repair (MMR)-deficient cells and tumor tissues, suggesting its role in chromosome stability associated with MMR deficiency. This study highlights a human-specific complexity in telomere protection and damage signaling conferred by functionally distinct isoforms from the single POT1 gene. C1 [Yang, Qin; Zhang, Ran; Horikawa, Izumi; Fujita, Kaori; Afshar, Yalda; Harris, Curtis C.] NIH, Natl Canc Inst, Canc Res Ctr, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Kokko, Antti; Laiho, Paivi; Aaltonen, Lauri A.] Univ Helsinki, Dept Med Genet, Mol & Canc Biol Res Program, Helsinki, Finland. RP Harris, CC (reprint author), NIH, Natl Canc Inst, Canc Res Ctr, Human Carcinogenesis Lab, Bldg 37,Room 3068A,37 Convent Dr, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov FU Intramural NIH HHS NR 48 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2007 VL 67 IS 24 BP 11677 EP 11686 DI 10.1158/0008-5472.CAN-07-1390 PG 10 WC Oncology SC Oncology GA 244HV UT WOS:000251857900027 PM 18089797 ER PT J AU Horak, CE Mendoza, A Vega-Valle, E Albaugh, M Graff-Cherry, C McDermott, WG Hua, E Merino, MJ Steinberg, SM Khanna, C Steeg, PS AF Horak, Christine E. Mendoza, Arnulfo Vega-Valle, Eleazar Albaugh, Mary Graff-Cherry, Cari McDermott, William G. Hua, Emily Merino, Maria J. Steinberg, Seth M. Khanna, Chand Steeg, Patricia S. TI Nm23-H1 suppresses metastasis by inhibiting expression of the lysophosphatidic acid receptor EDG2 SO CANCER RESEARCH LA English DT Article ID BREAST-CARCINOMA CELLS; KINASE ALPHA-ISOFORM; DIPHOSPHATE KINASE; CANCER CELLS; IN-VITRO; ADENOCARCINOMA CELLS; BONE METASTASES; SRC ACTIVATION; MELANOMA-CELLS; TRANSFECTION AB Nm23-H1 transcriptionally down-regulates expression of the lysophosphatidic acid receptor EDG2 and this down-regulation is critical for Nm23-H1-mediated motility suppression in vitro. We investigated the effect of altered EDG2 expression on Nm23-H1-mediated metastasis suppression in vivo. Clonal MDA-MB-435-derived tumor cell lines transfected with Nm23-H1 together with either a vector control or EDG2 had similar anchorage-dependent and anchorage-independent growth rates in vitro. However, a 45- and 300-fold inhibition of motility and invasion (P < 0.0001), respectively, was observed in Nm23-H1/vector lines, whereas coexpression of EDG2 restored activity to levels observed in the parental line. Using fluorescently labeled cells and ex vivo microscopy, the capacity of these cells to adhere, arrest, extravasate, and survive in the murine lung over a 24-h time course was measured. Only 5% of Nm23-H1/vector-transfected cells were retained in the murine lung 6 h following tail vein injection; coexpression of EDG2 enhanced retention 8- to 13-fold (P < 0.01). In a spontaneous metastasis assay, the primary tumor size of Nm23-H1/vector and Nm23-H1/EDG2 clones was not significantly different. However, restoration of EDG2 expression augmented the incidence of pulmonary metastasis from 51.9% to 90.4% (P = 2.4 X 10(-5)), comparable with parental MDA-MB-435 cells. To determine the relevance of this model system to human breast cancer, a cohort of breast carcinomas was stained for Nm23-H1 and EDG2 and a statistically significant inverse correlation between these two proteins was revealed (r = -0.73; P = 0.004). The data indicate that Nm23-H1 down-regulation of EDG2 is functionally important to suppression of tumor metastasis. C1 [Horak, Christine E.; Hua, Emily; Steeg, Patricia S.] NCI, Canc Res Ctr, Mol Pharmacol Lab, Womens Canc Sect, Bethesda, MD 20892 USA. [Mendoza, Arnulfo; Khanna, Chand] NCI, Canc Res Ctr, Pediat Oncol Branch, Tumor & Metastasis Biol Sect, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Canc Res Ctr, Pathol Lab, Surg Pathol Sect, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Canc Res Ctr, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Vega-Valle, Eleazar; Albaugh, Mary; Graff-Cherry, Cari] NCI, Sci Applicat Int Corp Frederick Inc, Ctr Canc Res, Frederick, MD 21701 USA. RP Horak, CE (reprint author), NCI, Canc Res Ctr, Mol Pharmacol Lab, Womens Canc Sect, 37 Convent Dr, Bethesda, MD 20892 USA. EM horakc@mail.nin.gov FU Intramural NIH HHS NR 45 TC 56 Z9 58 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2007 VL 67 IS 24 BP 11751 EP 11759 DI 10.1158/0008-5472.CAN-07-3175 PG 9 WC Oncology SC Oncology GA 244HV UT WOS:000251857900035 PM 18089805 ER PT J AU Ganguly, A Das, B Roy, A Sen, N Dasgupta, SB Mukhopadhayay, S Majumder, HK AF Ganguly, Agneyo Das, Benubrata Roy, Amit Sen, Nilkantha Dasgupta, Somdeb Bose Mukhopadhayay, Sibabrata Majumder, Hemanta K. TI Betulinic acid, a catalytic inhibitor of topoisomerase I, inhibits reactive oxygen species-mediated apoptotic topolsomerase I-DNA cleavable complex formation in prostate cancer cells but does not affect the process of cell death SO CANCER RESEARCH LA English DT Article ID MITOCHONDRIAL DYSFUNCTION; LEISHMANIA-DONOVANI; RADICALS; THERAPY; DAMAGE AB The ubiquitious enzyme topoisomerase I can be targeted by drugs which turn these enzymes into cellular poisons and subsequently induce cell death. Drugs like staurosporine, which do not target topoisomerase I directly, can also lead to stabilization of topoisomerase I-DNA cleavable complexes by an indirect process of reactive oxygen species (ROS) generation and subsequent oxidative DNA damage. In this study, we show that betulinic acid, a catalytic inhibitor of topoisomerases, inhibits the formation of apoptotic topoisomerase I-DNA cleavable complexes in prostate cancer cells induced by drugs like camptothecin, staurosporine, and etoposide. Although events like ROS generation, oxidative DNA damage, and DNA fragmentation were observed after betulinic acid treatment, there is no topoisomerase I-DNA cleavable complex formation, which is a key step in ROS-induced apoptotic processes. We have shown that betulinic acid interacts with cellular topoisomerase I and prohibits its interaction with the oxidatively damaged DNA. Using oligonucleotide containing 8-oxoguanosine modification, we have shown that betulinic acid inhibits its cleavage by topoisomerase I in vitro. Whereas silencing of topoisomerase I gene by small interfering RNA reduces cell death in the case of staurosporine and camptothecin, it cannot substantially reduce betulinic acid-induced cell death. Thus, our study provides evidence that betulinic acid inhibits formation of apoptotic topoisomerase I-DNA complexes and prevents the cellular topoisomerase I from directly participating in the apoptotic process. C1 [Ganguly, Agneyo; Roy, Amit; Dasgupta, Somdeb Bose; Majumder, Hemanta K.] Indian Inst Chem Biol, Mol Parasitol Lab, Kolkata, W Bengal, India. [Mukhopadhayay, Sibabrata] Indian Inst Chem Biol, Dept Med Chem, Kolkata, W Bengal, India. [Das, Benubrata] NIH, Natl Canc Inst, Mol Pharmacol Lab, Bethesda, MD USA. [Sen, Nilkantha] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD USA. RP Majumder, HK (reprint author), Indian Inst Chem Biol, 4 Raja Sc Mullick Rd, Kolkata 700032, W Bengal, India. EM hkmajumder@iicb.res.in NR 26 TC 47 Z9 47 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2007 VL 67 IS 24 BP 11848 EP 11858 DI 10.1158/0008-5472.CAN-07-1615 PG 11 WC Oncology SC Oncology GA 244HV UT WOS:000251857900045 PM 18089815 ER PT J AU Pereira-Faca, SR Kuick, R Puravs, E Zhang, Q Krasnoselsky, AL Phanstiel, D Qiu, J Misek, DE Hinderer, R Tammemagi, M Landi, MT Caporaso, N Pfeiffer, R Edelstein, C Goodman, G Barnett, M Thornquist, M Brenner, D Hanash, SM AF Pereira-Faca, Sandra R. Kuick, Rork Puravs, Eric Zhang, Qing Krasnoselsky, Alexei L. Phanstiel, Douglas Qiu, Ji Misek, David E. Hinderer, Robert Tammemagi, Martin Landi, Maria Teresa Caporaso, Neil Pfeiffer, Ruth Edelstein, Cim Goodman, Gary Barnett, Matt Thornquist, Mark Brenner, Dean Hanash, Samir M. TI Identification of 14-3-3 theta as an antigen that induces a humoral response in lung cancer SO CANCER RESEARCH LA English DT Article ID IMMUNE-RESPONSE; TUMOR-ANTIGEN; AUTOANTIBODIES; PROTEOMICS; PROTEINS; PHOSPHORYLATION; 14-3-3-ZETA; BINDING; MARKER; SYSTEM AB We have implemented a strategy to identify tumor antigens that induce a Immoral immune response in lung cancer based on the analysis of tumor cell proteins. Chromatographically fractionated protein extracts from three lung cancer cell lines were subjected to Western blotting and hybridization with individual sera to determine serum antibody binding. Two sets of sera were initially investigated. One set consisted of sera from 19 newly diagnosed subjects with lung adenocarcinoma and 19 matched controls. A second independent set consisted of sera from 26 newly diagnosed subjects with lung adenocarcinoma and 24 controls matched for age, gender, and smoking history. One protein that exhibited significant reactivity with both sets of cancer sera (P = 0.0008) was confidently identified by mass spectrometry as 14-3-3 theta. Remarkably, significant autoantibody reactivity against 14-3-3 theta was also observed in an analysis of a third set consisting of IS prediagnostic lung cancer sera collected as part of the Beta-Carotene and Retinol Efficacy Trial cohort study, relative to 19 matched controls (P = 0.0042). A receiver operating characteristic curve constructed with a panel of three proteins consisting of 14-3-3 theta identified in this study, plus annexin I and protein gene product 9.5 proteins previously identified as associated with autoantibodies in lung cancer, gave a sensitivity of 55% at 95% specificity (area under the curve, 0.838) in discriminating lung cancer at the preclinical stage from matched controls. C1 [Pereira-Faca, Sandra R.; Zhang, Qing; Krasnoselsky, Alexei L.; Phanstiel, Douglas; Qiu, Ji; Edelstein, Cim; Goodman, Gary; Barnett, Matt; Thornquist, Mark; Hanash, Samir M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Kuick, Rork; Puravs, Eric; Misek, David E.; Hinderer, Robert] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Kuick, Rork; Brenner, Dean] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Tammemagi, Martin] Brock Univ, St Catharines, ON L2S 3A1, Canada. [Landi, Maria Teresa; Caporaso, Neil; Pfeiffer, Ruth] NIH, Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hanash, SM (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M5-C800, Seattle, WA 98109 USA. EM shanash@fhcrc.org RI Pfeiffer, Ruth /F-4748-2011 NR 34 TC 54 Z9 55 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2007 VL 67 IS 24 BP 12000 EP 12006 DI 10.1158/0008-5472.CAN-07-2913 PG 7 WC Oncology SC Oncology GA 244HV UT WOS:000251857900061 PM 18089831 ER PT J AU Vandenbosch, R Borgs, L Beukelaers, P Foidart, A Nguyen, L Moonen, G Berthet, C Kaldis, P Gallo, V Belachew, S Malgrange, B AF Vandenbosch, Renaud Borgs, Laurence Beukelaers, Pierre Foidart, Agnes Nguyen, Laurent Moonen, Gustave Berthet, Cyril Kaldis, Philipp Gallo, Vittorio Belachew, Shibeshih Malgrange, Brigitte TI CDK2 is dispensable for adult hippocampal neurogenesis SO CELL CYCLE LA English DT Article DE cell cycle; adult neurogenesis; hippocampus; apoptosis; seizure ID INJURY-INDUCED NEUROGENESIS; CYCLIN-DEPENDENT KINASES; CELL-CYCLE; DENTATE GYRUS; PROLIFERATION; NEURONS; PROGENITORS; INHIBITION; PLASTICITY; APOPTOSIS AB Granule neurons of the dentate gyrus (DG) of the hippocampus undergo continuous renewal throughout life. Among cell cycle regulators, cyclin-dependent kinase 2 (Cdk2) is considered as a major regulator of S-phase entry. We used Cdk2-deficient mice to decipher the requirement of Cdk2 for the generation of new neurons in the adult hippocampus. The quantification of cell cycle markers first revealed that the lack of Cdk2 activity does not influence spontaneous or seizure-induced proliferation of neural progenitor cells (NPC) in the adult DG. Using bromodeoxyuridine incorporation assays, we showed that the number of mature newborn granule neurons generated de novo was similar in both wild-type (WT) and Cdk2-deficient adult mice. Moreover, the apparent lack of cell output reduction in Cdk2(-/)-mice DG did not result from a reduction in apoptosis of newborn granule cells as analyzed by TUNEL assays. Our results therefore suggest that Cdk2 is dispensable for NPC proliferation, differentiation and survival of adult-born DG granule neurons in vivo. These data emphasize that functional redundancies between Cdks also occur in the adult brain at the level of neural progenitor cell cycle regulation during hippocampal neurogenesis. C1 [Vandenbosch, Renaud; Borgs, Laurence; Beukelaers, Pierre; Foidart, Agnes; Nguyen, Laurent; Moonen, Gustave; Belachew, Shibeshih; Malgrange, Brigitte] Univ Liege, Ctr Cellular & Mol Neurosci, B-4000 Liege, Belgium. [Moonen, Gustave; Belachew, Shibeshih] CHU Sart Tilman, Dept Neurol, B-4000 Liege, Belgium. [Berthet, Cyril; Kaldis, Philipp] NIH, NCI, Frederick, MD USA. [Gallo, Vittorio] Childrens Natl Med Ctr, Ctr Res Neurosci, Washington, DC 20010 USA. RP Vandenbosch, R (reprint author), Univ Liege, Ctr Cellular & Mol Neurosci, Ave Hop 1, Batiment B36, B-4000 Liege, Belgium. EM renaud.vandenbosch@student.ulg.ac.be RI Kaldis, Philipp/G-2714-2010; OI Kaldis, Philipp/0000-0002-7247-7591; Malgrange, Brigitte/0000-0002-8957-2528 NR 34 TC 15 Z9 15 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC 15 PY 2007 VL 6 IS 24 BP 3065 EP 3069 PG 5 WC Cell Biology SC Cell Biology GA 258OK UT WOS:000252877000013 PM 18073538 ER PT J AU Dmitrieva, NI Burg, MB AF Dmitrieva, Natalia I. Burg, Maurice B. TI High NaCl promotes cellular senescence SO CELL CYCLE LA English DT Article DE NaCl; senescence; aging; DNA damage; osmotic stress; C. elegans; kidney ID MURINE KIDNEY-CELLS; RENAL-CELLS; IN-VIVO; CHROMOSOMAL-ABERRATIONS; MOLECULAR CHAPERONES; SERIAL CULTIVATION; SODIUM-CHLORIDE; TUMOR-CELLS; DNA-DAMAGE; LIFE-SPAN AB High extracellular NaCl was previously shown to increase the number of DNA breaks in mammalian cells in tissue culture, renal medullary cells in vivo, C. elegans and marine invertebrates. It was also shown to increase reactive oxygen species in renal cells, resulting in oxidation of proteins and DNA. Cellular senescence is a common response to such damage. Therefore, in the present studies we looked for signs of senescence in cells exposed to high NaCl. We find that (1) the rate of proliferation of HeLa cells exposed to high NaCl decreases gradually to the point of arrest, and the cells display signs of senescence, including hypertrophy and increased auto fluorescence. (2) High NaCl accelerates the appearance of senescence in primary mouse embryonic fibroblasts, as measured by senescence-associated beta-galactosidase activity (SA-beta-gal). (3) High NaCl retards growth and markedly decreases the life span of C. elegans, accompanied by features of accelerated aging, such as decreased locomotion and increased number of SA-beta-gal positive cells. (4) Mouse renal medullary cells, which are normally continuously exposed to high NaCl, express increased p16(INK4) (another indicator of senescence) much earlier than do cells in the renal cortex, which has the same level of NaCl as peripheral blood. We conclude that high NaCl accelerates cellular senescence and aging, most likely secondary to the DNA breaks and oxidative damage that it causes. C1 [Dmitrieva, Natalia I.; Burg, Maurice B.] NIH, NHLBI, Dept Hlth & Human Serv, Lab Kidney & Electrolyte Metab, Bethesda, MD 20892 USA. RP Dmitrieva, NI (reprint author), NIH, NHLBI, Lab Kidney & Electrolyte Metab, 9000 Rockville Pike,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. EM dmitrien@nhlbi.nih.gov RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 FU Intramural NIH HHS NR 63 TC 15 Z9 15 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC 15 PY 2007 VL 6 IS 24 BP 3108 EP 3113 PG 6 WC Cell Biology SC Cell Biology GA 258OK UT WOS:000252877000019 PM 18073528 ER PT J AU Wang, E Selleri, S Marincola, FM AF Wang, Ena Selleri, Silvia Marincola, Francesco M. TI The requirements for CTL-mediated rejection of cancer in humans: NKG2D and its role in the immune responsiveness of melanoma SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID T-CELL SUBSETS; PERIPHERAL-BLOOD; IMMUNOTHERAPY; IMMUNIZATION; PEPTIDE C1 [Wang, Ena; Selleri, Silvia; Marincola, Francesco M.] NIH, Ctr Clin, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Ctr Clin, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bldg 10,Room 1C-711,10 Ctr Dr MSA 1502, Bethesda, MD 20892 USA. EM Fmarincola@mail.cc.nih.gov NR 25 TC 6 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2007 VL 13 IS 24 BP 7228 EP 7231 DI 10.1158/1078-0432.CCR-07-2150 PG 4 WC Oncology SC Oncology GA 245RT UT WOS:000251954200002 PM 18094399 ER PT J AU Rixe, O Fojo, T AF Rixe, Olivier Fojo, Tito TI Is cell death a critical end point for anticancer therapies or is cytostasis sufficient? SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; BREAST-CANCER CELLS; OVARIAN-CANCER; IN-VITRO; SIGNALING PATHWAYS; LAPATINIB GW572016; INHIBITOR; APOPTOSIS; AGENTS; FLAVOPIRIDOL AB Since the discovery of conventional chemotherapy and the development of new target-based agents, the importance of cytostasis in anticancer activity has been debated. This review examines the relative importance of both cytostasis and cytotoxicity based on both preclinical data and clinical reports. Several limitations of our basic and clinical methods to evaluate cytostasis and cytotoxicity will be highlighted. Molecular mechanisms of cytostasis will be analyzed, including interference with the cell cycle as well as putative links with necrosis and autophagy. Finally, we will cite evidence that most older and newer compounds are both cytostatic and cytotoxic. The relative role of cytostasis and cytotoxicity on future drug screening and clinical development will be explored. C1 [Rixe, Olivier] Univ Paris 06, Salpetriere Hosp, Dept Med Oncol, Paris, France. [Fojo, Tito] Natl Canc Inst, Med Oncol Branch, Canc Res Ctr, Bethesda, MD USA. RP Rixe, O (reprint author), Hop La Pitie Salpetriere, Med Oncol Serv, 47 Bd Hop, F-75013 Paris, France. EM olivier.rixe@yahoo.com NR 56 TC 68 Z9 68 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2007 VL 13 IS 24 BP 7280 EP 7287 DI 10.1158/1078-0432.CCR-07-2141 PG 8 WC Oncology SC Oncology GA 245RT UT WOS:000251954200012 PM 18094408 ER PT J AU Kuhn, JG Chang, SM Wen, PY Cloughesy, TF Greenberg, H Schiff, D Conrad, C Fink, KL Robins, HI Mehta, M DeAngelis, L Raizer, J Hess, K Lamborn, KR Dancey, J Praclos, MD AF Kuhn, John G. Chang, Susan M. Wen, Patrick Y. Cloughesy, Timothy F. Greenberg, Harry Schiff, David Conrad, Charles Fink, Karen L. Robins, H. Ian Mehta, Minesh DeAngelis, Lisa Raizer, Jeffrey Hess, Kenneth Lamborn, Kathleen R. Dancey, Janet Praclos, Michael D. TI Pharmacokinetic and tumor distribution characteristics of temsirolimus in patients with recurrent malignant glioma SO CLINICAL CANCER RESEARCH LA English DT Article ID MAMMALIAN TARGET; PHASE-II; GLIOBLASTOMA-MULTIFORME; CCI-779; CANCER; MTOR; INHIBITOR; SAFETY AB Purpose: To characterize the pharmacokinetics of temsirolimus and its major metabolite, sirolimus, in patients receiving enzyme-inducing antiepileptic drugs (EIAED) compared with patients receiving non-EIAEDs. An additional objective was to determine whether concentrations of temsirolimus or sirolimus were achieved in brain tumor tissue. Experimental Design: Patients with recurrent malignant gliomas not receiving EIAEDs initially received temsirolimus weekly at a dose of 250 mg i.v. The dose was subsequently reduced to 170 mg due to intolerable side effects. For patients taking EIAEDs, the starting dose of temsirolimus was 250 mg with standard dose escalation until the maximal tolerated dose was established. Ten whole blood samples were obtained over a period of 24 h after administration of temsirolimus for pharmacokinetic assessments. Patients eligible for cytoreductive surgery received temsirolimus before tumor resection. Whole blood and tumor tissue were obtained for analysis. Results: Significant differences in the pharmacokinetic variables for temsirolimus and sirolimus were observed between the two patient groups at a comparable dose level of 250 mg. For patients receiving EIAEDs, the systemic exposure to temsirolimus was lower by 1.5-fold. Likewise, peak concentrations and exposure to sirolimus were lower by 2-fold. Measurable concentrations of ternsirolimus and sirolimus were observed in brain tumor specimens. The average tissue to whole blood ratio for ternsirolimus was 1.43 and 0.84 for sirolimus. Conclusions: Drugs that induce cytochrome P450 3A4, such as EIAEDs, significantly affect the pharmacokinetics of ternsirolimus and its active metabolite, sirolimus. Total exposure to temsirolimus and sirolimus was lower in the EIAED group at the maximum tolerated dose of 250 mg compared with the non-EIAED group at the maximum tolerated dose of 170 mg. However, brain tumor tissue concentrations of ternsirolimus and sirolimus were relatively comparable in both groups of patients at their respective dose levels. Correlative analyses of the tissue for the inhibition of the key regulators (p70(S6) kinase and 4E-binding protein 1) of mammalian target of rapamycin are necessary to define the therapeutic significance of the altered exposure to temsirolimus. C1 [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Chang, Susan M.; Lamborn, Kathleen R.; Praclos, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Greenberg, Harry] Univ Michigan Hosp, Ann Arbor, MI 48109 USA. [Schiff, David] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22903 USA. [Conrad, Charles; Hess, Kenneth] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fink, Karen L.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Robins, H. Ian; Mehta, Minesh] Univ Wisconsin Hosp, Madison, WI USA. [DeAngelis, Lisa] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Raizer, Jeffrey] Northwestern Univ, Chicago, IL 60611 USA. [Dancey, Janet] NIH, Cancer Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Kuhn, JG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, 7703 Floyd Curl Dr,MSC 6220, San Antonio, TX 78229 USA. EM Kuhn@uthscsa.edu OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [U01CA62422, CA16672, CA62412, CA62455, P30 CA016672, P30 CA054174, P30CA54174, U01 CA062399, U01 CA062407, U01 CA062412, U01 CA062421, U01 CA062422, U01 CA062426, U01CA62339, U01CA62399, U01CA62407, U01CA62421, U01CA62426, UM1 CA137443]; NCRR NIH HHS [M01 RR000042, M01 RR000079, M01 RR000633, M01 RR000865, M01 RR003186, M01-RR00042, M01-RR00079, M01-RR00633, M01-RR03186, M01-RR0865] NR 17 TC 37 Z9 37 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2007 VL 13 IS 24 BP 7401 EP 7406 DI 10.1158/1078-0432.CCR-07-0781 PG 6 WC Oncology SC Oncology GA 245RT UT WOS:000251954200027 PM 18094423 ER PT J AU Zhuang, SH Hung, YE Hung, L Robey, RW Sackett, DL Linehan, WM Bates, SE Fojo, T Poruchynsky, MS AF Zhuang, Sen H. Hung, Y. Elizabeth Hung, Laura Robey, Robert W. Sackett, Dan L. Linehan, W. Marston Bates, Susan E. Fojo, Tito Poruchynsky, Marianne S. TI Evidence for microtubule target engagement in tumors of patients receiving ixabepilone SO CLINICAL CANCER RESEARCH LA English DT Article ID ALPHA-TUBULIN; POSTTRANSLATIONAL MODIFICATION; PACLITAXEL TAXOL(R); DESOXYEPOTHILONE-B; STABILIZING AGENTS; PURIFIED TUBULIN; EPOTHILONE-B; CANCER-CELLS; PHASE-I; RESISTANT AB Purpose: Microtubule-stabilizing agents, such as taxanes, have been shown to be effective anticancer drugs. alpha-Tubulin, a basic unit of microtubules, can undergo several posttranslational modifications after assembly into stabilized microtubules, including acetylation and detyrosination. These modifications have been observed in cell cultures after exposure to microtubule stabilizers. Our objective was to develop a straightforward and dependable assay to show tubulin target engagement in tumor tissue after treatment of patients with ixabepilone (BMS-247550; Ixempra). Experimental Design: Levels of posttranslationally modified alpha-tubulin were assessed in lysates of cultured malignant cell lines, as well as in both tumor tissue and peripheral blood mononuclear cells derived from patients before and after treatment with ixabepilone. Modification-specific antibodies permitted quantitative Western blot analysis. Results: In cultured cell lines, the levels of detyrosinated (glu-terminated) and acetylated a-tubulin increased after microtubule stabilization induced by ixabepilone. Ixabepilone treatment also induced a 2-fold to 25-fold increase in detyrosinated alpha-tubulin levels in 11 of 13 serial biopsies and a 2-fold to 100-fold increase in acetylated a-tubulin in 11 of 12 serial biopsies obtained from patients receiving ixabepilone. Overall, little or no difference in tubulin modifications were observed between the before and after ixabepilone treatment in lysates from their peripheral blood mononuclear cells at the time point examined. Conclusion: Assessing the levels of detyrosinated and/or acetylated alpha-tubulin seems to provide a simple and reliable assay to show target engagement by the microtubule-stabilizing agent ixabepilone. Such analyses may provide further understanding of therapeutic success or failure of microtubule-stabilizing agents in cancer therapy. C1 [Zhuang, Sen H.; Hung, Y. Elizabeth; Hung, Laura; Robey, Robert W.; Bates, Susan E.; Fojo, Tito; Poruchynsky, Marianne S.] NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. [Linehan, W. Marston] NIH, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD 20892 USA. [Sackett, Dan L.] NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NIH, Ctr Canc Res, Med Oncol Branch, Bldg 10,Room 12N226,Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov FU Intramural NIH HHS NR 38 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2007 VL 13 IS 24 BP 7480 EP 7486 DI 10.1158/1078-0432.CCR-06-2883 PG 7 WC Oncology SC Oncology GA 245RT UT WOS:000251954200036 PM 18094432 ER PT J AU Goulet, JL Fultz, SL Rimland, D Butt, A Gibert, C Rodriguez-Barradas, M Bryant, K Justice, AC AF Goulet, Joseph L. Fultz, Shawn L. Rimland, David Butt, Adeel Gibert, Cynthia Rodriguez-Barradas, Maria Bryant, Kendall Justice, Amy C. TI Do patterns of comorbidity vary by HIV status, age, and HIV severity? SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; VETERANS AGING COHORT; INFECTED VETERANS; PSYCHIATRIC COMORBIDITY; ADMINISTRATIVE DATA; POST-HAART; DISEASE; PERSPECTIVE; PROGNOSIS; ALCOHOL AB Patterns of comorbidity among persons with human immunodeficiency virus (HIV) are not well described. We compared comorbidity among veterans with and without HIV infection. The sample consisted of 33,420 HIV-infected veterans and 66,840 HIV-uninfected veterans. We identified and clustered 11 comorbid conditions using validated International Classification of Diseases, 9th Revision, Clinical Modification codes. We defined multimorbidity as the presence of conditions in all clusters. Models restricted to HIV-infected veterans were adjusted for CD4 cell count and viral load. Comorbidity was common (prevalence, 60%-63%), and prevalence varied by HIV status. Differences remained when the veterans were stratified by age. In multivariable analyses, older HIV-infected veterans were more likely to have substance use disorder and multimorbidity. Renal, vascular, and pulmonary diseases were associated with CD4 cell count < 200 cells/mm(3); hypertension was associated with CD4 cell count > 200 cells/mm(3). Comorbidity is the rule, and multimorbidity is common among veterans with HIV infection. Patterns of comorbidity differ substantially by HIV status, age, and HIV severity. Primary care guidelines require adaptation for persons with HIV infection. C1 [Goulet, Joseph L.; Justice, Amy C.] VA CT Hlthcare Syst, West Haven, CT 06516 USA. [Goulet, Joseph L.; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Fultz, Shawn L.] George Washington Univ, Med Ctr, Vet Hlth Adm, Washington, DC 20037 USA. [Gibert, Cynthia] George Washington Univ, Med Ctr, Vet Affairs Med Ctr, Washington, DC 20037 USA. [Rimland, David] Vet Affairs Med Ctr, Atlanta, GA 30033 USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Butt, Adeel] Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Butt, Adeel] Univ Pittsburgh, Pittsburgh, PA USA. [Rodriguez-Barradas, Maria] Michael E De Bakey Vet Affairs Med Ctr, Houston, TX USA. [Rodriguez-Barradas, Maria] Baylor Coll Med, Houston, TX 77030 USA. [Bryant, Kendall] NIH, NIAAA, Bethesda, MD 20892 USA. RP Goulet, JL (reprint author), VA CT Hlthcare Syst, 11ACSLG,Bldg 35A,Rm 2-207 950 Campbell Ave, West Haven, CT 06516 USA. EM joseph.goulet@med.va.gov OI Goulet, Joseph/0000-0002-0842-804X FU NIA NIH HHS [K23 AG00826]; NIAAA NIH HHS [U10 AA013566, U01 AA 13566, U01 AA013566, U10 AA 13566, U24 AA020794] NR 34 TC 134 Z9 136 U1 3 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2007 VL 45 IS 12 BP 1593 EP 1601 DI 10.1086/523577 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233HI UT WOS:000251081000011 PM 18190322 ER PT J AU Fauci, AS AF Fauci, Anthony S. TI Pathogenesis of HIV disease: Opportunities for new prevention interventions SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Conference on Opportunities for Improving HIV Diagnosis, Prevention and Access to Care in the United States CY NOV 29-30, 2006 CL Washington, DC SP Amer Acad HIV Med, amfAR, Ctr Dis Control & Prevent, Forum Collaborat HIV Res, HIV Med Assoc Infect Dis Soc Amer, NIAID ID IMMUNODEFICIENCY-VIRUS TYPE-1; MALE CIRCUMCISION; AIDS VACCINE; COITAL ACT; INFECTION; TRANSMISSION; STRATEGIES; UGANDA; RAKAI; TRIAL AB Current efforts to prevent human immunodeficiency virus (HIV) disease, which largely focus on altering human behavior, have had some notable successes yet have failed to halt the spread of the acquired immunodeficiency syndrome pandemic. A greater understanding of the pathogenesis of HIV disease is providing us with the scientific rationale for additional approaches to prevention. Some of the approaches discussed in this article are available now. For example, we have the means to screen for and treat other sexually transmitted diseases that increase vulnerability to HIV, adult male circumcision is readily available in most properly equipped hospitals, and antiretroviral agents that decrease the viral load help prevent transmission from pregnant women to their infants. Other approaches discussed are under investigation. For instance, numerous topical microbicides are in various stages of development, incremental progress is being made toward creation of an HIV vaccine designed to prevent HIV transmission or slow the course of disease in people who become infected, and studies are under way to evaluate the risks and benefits of prophylactic antiretroviral therapy in individuals at high risk for HIV disease. C1 [Fauci, Anthony S.] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, Natl Inst Hlth, Bldg 31, Rm 7A-03, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 41 TC 14 Z9 14 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2007 VL 45 SU 4 BP S206 EP S212 DI 10.1086/522540 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 240VA UT WOS:000251615100002 PM 18190288 ER PT J AU Estrada, B Gisselbrecht, SS Michelson, AM AF Estrada, Beatriz Gisselbrecht, Stephen S. Michelson, Alan M. TI The transmembrane protein Perdido interacts with Grip and integrins to mediate myotube projection and attachment in the Drosophila embryo SO DEVELOPMENT LA English DT Article DE muscle attachment; myotendinous junction; myogenesis; NG2; MCSP; integrins; Drosophila ID PS INTEGRINS; NG2 PROTEOGLYCAN; SITE SELECTION; PDZ DOMAINS; GUIDANCE; MORPHOGENESIS; EXPRESSION; RECEPTOR; EMBRYOGENESIS; INTERFERENCE AB The molecular mechanisms underlying muscle guidance and formation of myotendinous junctions are poorly understood both in vertebrates and in Drosophila. We have identified a novel gene that is essential for Drosophila embryonic muscles to form proper projections and stable attachments to epidermal tendon cells. Loss-of-function of this gene - which we named perdido (perd) results in rounded, unattached muscles. perd is expressed prior to myoblast fusion in a subset of muscle founder cells, and it encodes a conserved single-pass transmembrane cell adhesion protein that contains laminin globular extracellular domains and a small intracellular domain with a C-terminal PDZ-binding consensus sequence. Biochemical experiments revealed that the Perd intracellular domain interacts directly with one of the PDZ domains of the Glutamate receptor interacting protein (Grip), another factor required for formation of proper muscle projections. In addition, Perd is necessary to localize Grip to the plasma membrane of developing myofibers. Using a newly developed, whole-embryo RNA interference assay to analyze genetic interactions, perd was shown to interact not only with Grip but also with multiple edematous wings, which encodes one subunit of the alpha PS1-beta PS integrin expressed in tendon cells. These experiments uncovered a previously unrecognized role for the alpha PS1-beta PS integrin in the formation of muscle projections during early stages of myotendinous junction development. We propose that Perd regulates projection of myotube processes toward and subsequent differentiation of the myotendinous junction by priming formation of a protein complex through its intracellular interaction with Grip and its transient engagement with the tendon cell-expressed laminin-binding alpha PS1-beta PS integrin. C1 Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Genet, Boston, MA 02115 USA. Univ Pablo Olavide, CSIC, Ctr Andaluz Biol Desarrollo, E-41013 Seville, Spain. NIH, NHLBI, Bethesda, MD 20892 USA. RP Estrada, B (reprint author), Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM bestmar@upo.es; michelsonam@nhlbi.nih.gov OI Gisselbrecht, Stephen/0000-0001-8723-902X NR 41 TC 26 Z9 27 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC 15 PY 2007 VL 134 IS 24 BP 4469 EP 4478 DI 10.1242/dev.014027 PG 10 WC Developmental Biology SC Developmental Biology GA 235NI UT WOS:000251240700015 PM 18039972 ER PT J AU Rodriguez, CI Stewart, CL AF Rodriguez, Clara I. Stewart, Colin L. TI Disruption of the ubiquitin ligase HERC4 causes defects in spermatozoon maturation and impaired fertility SO DEVELOPMENTAL BIOLOGY LA English DT Article DE HERC4; HERC family; E3 ubiquitin ligase; spermatogenesis; male fertility defect ID GUANINE-NUCLEOTIDE EXCHANGE; CYTOPLASMIC DROPLETS; PROTEIN LIGASE; GIANT PROTEIN; RAB PROTEINS; HECT DOMAIN; MICE; SPERM; CELLS; SPERMATOGENESIS AB Spermatogenesis in mammals necessitates an extensive remodeling and loss of many cellular organelles and proteins as the spermatozoa undergo maturation. The removal of proteins and orgarrelles depends on the ubiquitin-proteasome pathway. Here we show that the E3 ubiquitin ligase Herc4, though ubiquitously expressed in all tissues, is most highly expressed in the testis, specifically during spermiogenesis. Mice homozygous for a Herc4 mutation are overtly normal; however, overall the males produce litter sizes some 50% smaller whereas female homozygotes show normal fertility. The reduced fertility in males is associated with about 50% of mature spermatozoa having reduced motility. Many of the spermatozoa possess an angulated tail with a cytoplasmic droplet being retained at the angulation. Our results show that Herc4 ligase is required for proper maturation and removal of the cytoplasmic droplet for the spermatozoon to become fully functional. Published by Elsevier Inc. C1 [Rodriguez, Clara I.; Stewart, Colin L.] NCI, Div Basic Sci, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Stewart, CL (reprint author), Inst Med Biol, 8A Biomed Grove,06-06 Immunos, Singapore 138648, Singapore. EM colin.stewart@imb.a-star.edu.sg RI Rodriguez, Clara/E-4835-2012; Rodriguez, Clara/E-5402-2012 NR 46 TC 26 Z9 31 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 15 PY 2007 VL 312 IS 2 BP 501 EP 508 DI 10.1016/j.ydbio.2007.09.053 PG 8 WC Developmental Biology SC Developmental Biology GA 242OF UT WOS:000251734300003 PM 17967448 ER PT J AU Coppey, M Berezhkovskii, AM Kim, Y Boettiger, AN Shvartsman, SY AF Coppey, Mathieu Berezhkovskii, Alexander M. Kim, Yoosik Boettiger, Alistair N. Shvartsman, Stanislav Y. TI Modeling the bicold gradient: Diffusion and reversible nuclear trapping of a stable protein SO DEVELOPMENTAL BIOLOGY LA English DT Article DE morphogen; pattern formation; dynamics; modelling; syncytium; bicoid; Drosophila; analysis ID EARLY DROSOPHILA EMBRYO; MORPHOGEN GRADIENT; GENE-EXPRESSION; BINDING; ESTABLISHMENT; TRANSPORT; DOMAINS; PATTERN AB The Bicoid gradient in the Drosophila embryo provided the first example of a morphogen gradient studied at the molecular level. The exponential shape of the Bicoid gradient had always been interpreted within the framework of the localized production, diffusion, and degradation model. We propose an alternative mechanism, which assumes no Bicoid degradation. The medium where the Bicoid gradient is formed and interpreted is very dynamic. Most notably, the number of nuclei changes over three orders of magnitude from fertilization, when Bicoid synthesis is initiated, to nuclear cycle 14 when most of the measurements were taken. We demonstrate that a model based on Bicoid diffusion and nucleocytoplasmic shuttling in the presence of the growing number of nuclei can account for most of the properties of the Bicoid concentration profile. Consistent with experimental observations, the Bicoid gradient in our model is established before nuclei migrate to the periphery of the embryo and remains stable during subsequent nuclear divisions. Published by Elsevier Inc. C1 [Coppey, Mathieu; Kim, Yoosik; Shvartsman, Stanislav Y.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Dept Chem & Chem Engn, Princeton, NJ 08544 USA. [Berezhkovskii, Alexander M.] NIH, Ctr Informat Technol, Div Computat Biosci, Math & Stat Computat Lab, Bethesda, MD 20892 USA. [Boettiger, Alistair N.] Univ Calif Berkeley, Dept Cell Biol & Mol, Berkeley, CA 94720 USA. RP Shvartsman, SY (reprint author), Princeton Univ, Lewis Sigler Inst Integrat Genom, Dept Chem & Chem Engn, Princeton, NJ 08544 USA. EM stas@priceton.edu RI Boettiger, Alistair/G-1988-2011 FU Intramural NIH HHS [Z99 CT999999] NR 28 TC 52 Z9 54 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 15 PY 2007 VL 312 IS 2 BP 623 EP 630 DI 10.1016/j.ydbio.2007.09.058 PG 8 WC Developmental Biology SC Developmental Biology GA 242OF UT WOS:000251734300013 PM 18001703 ER PT J AU Hayden, PJ Tewari, P Morris, DW Staines, A Crowley, D Nieters, A Becker, N de Sanjose, S Foretova, L Maynadie, M Cocco, PL Boffetta, P Brennan, P Chanock, SJ Browne, PV Lawler, M AF Hayden, Patrick J. Tewari, Prerna Morris, Derek W. Staines, Anthony Crowley, Dominique Nieters, Alexandra Becker, Nikolaus de Sanjose, Silvia Foretova, Lenka Maynadie, Marc Cocco, Pier Luigi Boffetta, Paolo Brennan, Paul Chanock, Stephen J. Browne, Paul V. Lawler, Mark TI Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma SO HUMAN MOLECULAR GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; CLASS SWITCH RECOMBINATION; NECROSIS-FACTOR-ALPHA; BREAST-CANCER RISK; TAG SNP SELECTION; MULTIPLE-MYELOMA; ASSOCIATION; HAPLOTYPES; VARIANTS; LYMPHOMA AB Cytogenetic analysis in myeloma reveals marked chromosomal instability. Both widespread genomic alterations and evidence of aberrant class switch recombination, the physiological process that regulates maturation of the antibody response, implicate the DNA repair pathway in disease pathogenesis. We therefore assessed 27 SNPs in three genes (XRCC3, XRCC4 and XRCC5) central to DNA repair in patients with myeloma and controls from the EpiLymph study and from an Irish hospital registry (n = 306 cases, 263 controls). For the haplotype-tagging SNP (htSNP) rs963248 in XRCC4, Allele A was significantly more frequent in cases than in controls (86.4 versus 80.8%; odds ratio 1.51; 95% confidence interval 1.10-2.08; P = 0.0133), as was the AA genotype (74 versus 65%) (P = 0.026). Haplotype analysis was performed using Unphased for rs963248 in combination with additional SNPs in XRCC4. The strongest evidence of association came from the A-T haplotype from rs963248-rs2891980 (P = 0.008). For XRCC5, the genotype GG from rs1051685 was detected in 10 cases from different national populations but in only one control (P = 0.015). This SNP is located in the 3'-UTR of XRCC5. Overall, these data provide support for the hypothesis that common variation in the genes encoding DNA repair proteins contributes to susceptibility to myeloma. C1 Univ Dublin Trinity Coll, Inst Mol Med, Durkan Leukaemia Labs, Dept Haematol, Dublin 2, Ireland. Univ Dublin Trinity Coll, Inst Mol Med, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 2, Ireland. Univ Coll Dublin, Sch Publ Hlth & Populat Sci, Dublin 2, Ireland. German Canc Res Ctr, Div Epidemiol, D-6900 Heidelberg, Germany. Municipal Inst Med Res, Barcelona, Spain. Masaryk Mem Canc Inst, Brno, Czech Republic. Dijon Univ Hosp, Unit Biol Haematol, Dijon, France. Univ Cagliari, Inst Occupat Med, Cagliari, Italy. Int Agcy Res Canc, F-69372 Lyon, France. NCI, Core Genotyping Facil, Adv Technol Corp, Gaithersburg, MD USA. RP Lawler, M (reprint author), St James Hosp, Trinity Ctr, Inst Mol Med, Durkan Leukaemia Labs, Dublin 8, Ireland. EM mplawler@tcd.ie RI ODOnnell, Jim/C-2454-2009; de Sanjose Llongueras, Silvia/H-6339-2014; OI Morris, Derek/0000-0002-3413-570X; Staines, Anthony/0000-0001-9161-1357; Browne, Paul/0000-0001-5310-1487 NR 49 TC 36 Z9 39 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2007 VL 16 IS 24 BP 3117 EP 3127 DI 10.1093/hmg/ddm273 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 232RH UT WOS:000251036500014 PM 17901044 ER PT J AU Kopf, H De la Rosa, GM Howard, OMZ Chen, X AF Kopf, Heather De la Rosa, Gonzalo M. Howard, O. M. Zack Chen, Xin TI Rapamycin inhibits differentiation of Th17 cells and promotes generation of FoxP3+T regulatory cells SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE rapamycin; CD4(+)CD25(+)FoxP3(+) T regulatory cells; Th17 cells ID T-CELLS; TGF-BETA; AUTOIMMUNE-DISEASE; PERTUSSIS TOXIN; CYCLOSPORINE; T(H)17; IL-2; INDUCTION; TOLERANCE; LINEAGE AB Reciprocal differentiation of immunosuppressive CD4(+)CD25(+)FoxP3(+) T regulatory cells (Tregs) and proinflammatory IL-17-producing cells (Th17) from naive CD4 cells is contingent upon the cytokine environment. Using MACS-putified CD4 cells, we found that rapamycin and cyclosporine A (CsA) potently inhibited the TGF beta and IL-6-induced generation of IL-17-producing cells. Intriguingly, rapamycin promoted, while CsA markedly inhibited, TGF beta-mediated generation of Tregs. The aforementioned effects of rapamycin and CsA were also observed for Flow-sorted CD4(+)CD25(-) T cells, indicating that the effect of these two immunosuppressive agents was based on their action on de novo generation of Tregs and Th17 cells from naive CD4 cells. Our observation suggests a distinct mode of immunosuppressive action and tolerance induction by rapamycin and CsA. The capacity of rapamycin to generate immunosuppressive Tregs and to suppress differentiation of pathogenic Th17 cells furthers our understanding of the basis for the therapeutic immunosuppressive effects of rapamycin in patients with autoimmune diseases and allo-transplantation reactions. Published by Elsevier B.V. C1 [Chen, Xin] NCI Frederick, SAIC Frederick, Basic Res Program, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. [Kopf, Heather; De la Rosa, Gonzalo M.; Howard, O. M. Zack] NCI Frederick, Canc Res Ctr, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. RP Chen, X (reprint author), NCI Frederick, SAIC Frederick, Basic Res Program, Mol Immunoregulat Lab, POB B,Bldg 560,Rm 31-19, Ft Detrick, MD 21702 USA. EM chenxin@mail.nih.gov RI Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015 OI Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027 FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N01CO12400] NR 21 TC 126 Z9 140 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD DEC 15 PY 2007 VL 7 IS 13 BP 1819 EP 1824 DI 10.1016/j.intimp.2007.08.027 PG 6 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 240AV UT WOS:000251560300027 PM 17996694 ER PT J AU Srivastava, M Torosyan, Y Raffeld, M Eidelman, O Pollard, HB Bubendorf, L AF Srivastava, Meera Torosyan, Yelizaveta Raffeld, Mark Eidelman, Ofer Pollard, Harvey B. Bubendorf, Lukas TI ANXA7 expression represents hormone-relevant tumor suppression in different cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE annexin A7 (synexin); NKX3.1; cancer biomarker; tumor suppressor; tissue microarrays ID HOMEOBOX GENE NKX3.1; PROSTATE-CANCER; ANNEXIN-VII; CHROMAFFIN GRANULES; PROTEIN EXPRESSION; STEROID SULFATASE; MEMBRANE-VESICLES; CHROMOGRANIN-A; CELLS; PHENOTYPE AB Tumor suppressor function of ubiquitously expressed Annexin-A7, ANXA7 (10q21) that is involved in exocytosis and membrane fusion was based on cancer prone phenotype in Anxa7(+/-) mice as well as ANXA7 role in human prostate and breast cancers. To clarify ANXA7 biomarker and tumor suppressor function, we analyzed its expression pattern in comparison to the prostate-specific biomarker NKX3.1. lmmunohistochemistry-based ANXA7 and NKX3.1 protein expression was analyzed on human tissue microarrays of 4,061 specimens from a wide spectrum of the histopathologically well-characterized tumors in different stages compared to corresponding normal tissues. Decreased ANXA7 expression was mostly associated with high invasive potential in multiple tumors. Although some metastases retained relatively high ANXA7 rates compared to primary cancer tissues, the lymph node metastases from different sites (including prostate and breast) had decreased ANXA7 expression in comparison to the intact lymphatic tissues. Major ANXA7 downregulation pattern was deviated in tumors of glandular (especially neuroendocrine) origin. ANXA7 and NKX3.1 proteins were synexpressed in the male urogenital system and adrenal gland. Gene expression profiling in prostate and breast cancers (SMD) revealed distinct hormone-related profiles for NKX3.1 and ANXA7, where ANXA7 expression correlated with steroid sulfatase which has a pivotal role in steroidogenesis. Abundant protein presence in adrenal gland and its loss in hormone-refractory prostate cancer indicated that ANXA7 can be relevant to steroidogenesis and androgen sensitivity in particular. With tumor suppressor pattern validated in different tumors, ANXA7 can be an attractive diagnostic and therapeutic target associated with the hormone and/or neurotransmitter-mediated modulation of tumorigenesis. (c) 2007 Wiley-Liss, Inc. C1 Uniformed Serv Univ Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. Uniformed Serv Univ Sch Med, Inst Mol Med, Bethesda, MD 20814 USA. NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. Univ Hosp, Inst Pathol, Basel, Switzerland. RP Srivastava, M (reprint author), Uniformed Serv Univ Sch Med, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM msrivastava@usuhs.mil RI Bubendorfl, Lukas/H-5880-2011 NR 57 TC 28 Z9 37 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 2007 VL 121 IS 12 BP 2628 EP 2636 DI 10.1002/ijc.23008 PG 9 WC Oncology SC Oncology GA 233RW UT WOS:000251109000007 PM 17708571 ER PT J AU Bell, DW Kim, SH Godwin, AK Schiripo, TA Harris, PL Haserlat, SM Wahrer, DCR Haiman, CA Daly, MB Niendorf, KB Smith, MR Sgroi, DC Garber, JE Olopade, OI Le Marchand, L Henderson, BE Altshuler, D Haber, DA Freedman, ML AF Bell, Daphne W. Kim, Sang H. Godwin, Andrew K. Schiripo, Taryn A. Harris, Patricia L. Haserlat, Sara M. Wahrer, Doke C. R. Haiman, Christopher A. Daly, Mary B. Niendorf, Kristin B. Smith, Matthew R. Sgroi, Dennis C. Garber, Judy E. Olopade, Olufunmilayo I. Le Marchand, Loic Henderson, Brian E. Altshuler, David Haber, Daniel A. Freedman, Matthew L. TI Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cHEK2; susceptibility; breast; cancer; mutation ID DNA-DAMAGE CHECKPOINT; HEREDITARY BREAST-CANCER; TUMOR-SUPPRESSOR; PROSTATE-CANCER; PROTEIN-KINASE; FHA DOMAIN; MUTATION ANALYSIS; BRCA1 MUTATIONS; CHEK2-ASTERISK-1100DELC; RISK AB The CHEK2-1100delC mutation is recurrent in the population and is a moderate risk factor for breast cancer. To identify additional CHEK2 mutations potentially contributing to breast cancer susceptibility, we sequenced 248 cases with early-onset disease; functionally characterized new variants and conducted a population-based case-control analysis to evaluate their contribution to breast cancer risk. We identified 1 additional null mutation and 5 missense variants in the germline of cancer patients. In vitro, the CHEK2-H143Y variant resulted in gross protein destabilization, while others had variable suppression of in vitro kinase activity using BRCA1 as a substrate. The germline CHEK2-1100delC mutation was present among 8/1,646 (0.5%) sporadic, 2/400 (0.5%) early-onset and 3/302 (1%) familial breast cancer cases, but undetectable amongst 2,105 multiethnic controls, including 633 from the US. CHEK2-positive breast cancer families also carried a deleterious BRCA1 mutation. 1100delC appears to be the only recurrent CHEK2 mutation associated with a potentially significant contribution to breast cancer risk in the general population. Another recurrent mutation with attenuated in vitro function, CHEK2-P85L, is not associated with increased breast cancer susceptibility, but exhibits a striking difference in frequency across populations with different ancestral histories. These observations illustrate the importance of genotyping ethnically diverse groups when assessing the impact of low-penetrance susceptibility alleles on population risk. Our findings highlight the notion that clinical testing for rare missense mutations within CHEK2 may have limited value in predicting breast cancer risk, but that testing for the 1100delC variant may be valuable in phenotypically- and geographically-selected populations. (c) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Dana Farber Canc Inst, Ctr Populat Sci, Dept Oncol, Boston, MA 02115 USA. Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Broad Inst Biomed Res, Boston, MA USA. RP Bell, DW (reprint author), NHGRI, NIH, Canc Genet Branch, Room 5339,Bldg 50,50 S Dr,MSC 8000, Bethesda, MD 20892 USA. EM belldaph@mail.nih.gov RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU Intramural NIH HHS; NCI NIH HHS [K24 CA121990, R01 CA063464, K24 CA121990-02, CA63464, CA87691, U01 CA063464] NR 52 TC 39 Z9 39 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 2007 VL 121 IS 12 BP 2661 EP 2667 DI 10.1002/ijc.23026 PG 7 WC Oncology SC Oncology GA 233RW UT WOS:000251109000011 PM 17721994 ER PT J AU Freedman, ND Park, Y Subar, AF Hollenbeck, AR Leitzmann, MF Schatzkin, A Abnet, CC AF Freedman, Neal D. Park, Yikyung Subar, Amy F. Hollenbeck, Albert R. Leitzmann, Michael F. Schatzkin, Arthur Abnet, Christian C. TI Fruit and vegetable intake and esophageal cancer in a large prospective cohort study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE esophageal cancer; fruits; vegetables; cohort ID BODY-MASS INDEX; GASTRIC CARDIA; FOOD GROUPS; DIETARY-INTAKE; UNITED-STATES; RISK; ADENOCARCINOMA; POPULATION; PREVENTION; CLASSIFICATION AB Changing patterns of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) incidence worldwide suggest distinct etiologies. Although associations between fruit and vegetable intake and both ESCC and EAC have been found in multiple ecological and case-control studies, few prospective studies have investigated these associations. We prospectively examined these associations in 490,802 participants of the National Institutes of Health (NIH)-AARP Diet and Health Study using Cox models adjusted for age, alcohol intake, body mass index, cigarette smoking, education, physical activity and total energy intake. We present hazard ratios and 95% confidence intervals per serving per 1,000 calories. During 2,193,751 person years of follow-up, 103 participants were diagnosed with ESCC and 213 participants with EAC. We found a significant inverse association between total fruit and vegetable intake and ESCC risk (HR: 0.78, 95% CI: 0.67-0.91), but not EAC risk (0.98, 0.90-1.08). In models mutually adjusted for fruit and vegetable intake, the protective association with ESCC was stronger for fruits (0.73, 0.57-0.93) than for vegetables (0.84, 0.66-1.07). When we examined botanical subgroups, we observed significant protective associations for ESCC and intake of Rosacea (apples, peaches, nectarines, plums, pears and strawberries) and Rutaceae (citrus fruits). A significant inverse association between EAC and Chenopodiaceae (spinach) intake was observed. Results from our study suggest that the relation of fruit and vegetable intake and esophageal cancer risk may vary by histologic type. (c) 2007 Wiley-Liss, Inc. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, NIH, DHHS, Rockville, MD USA. AARP, Washington, DC USA. RP Freedman, ND (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS-320,MSC 7232, Rockville, MD 20852 USA. EM freedmanne@mail.nih.gov RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015; OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098; Park, Yikyung/0000-0002-6281-489X FU Intramural NIH HHS NR 46 TC 72 Z9 76 U1 1 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 2007 VL 121 IS 12 BP 2753 EP 2760 DI 10.1002/ijc.22993 PG 8 WC Oncology SC Oncology GA 233RW UT WOS:000251109000025 PM 17691111 ER PT J AU Gravitt, PE Kovacic, MB Herrero, R Schiffman, M Bratti, C Hildesheim, A Morales, J Alfaro, M Sherman, ME Wacholder, S Rodriguez, AC Burk, RD AF Gravitt, Patti E. Kovacic, Melinda Butsch Herrero, Rolando Schiffman, Mark Bratti, Concepcion Hildesheim, Allan Morales, Jorge Alfaro, Mario Sherman, Mark E. Wacholder, Sholorn Rodriguez, Ana-Cecilia Burk, Robert D. TI High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE human papillomavirus; viral load; genotype; screening ID CARCINOMA IN-SITU; VIRAL LOAD; INTRAEPITHELIAL NEOPLASIA; COSTA-RICA; INFECTION; WOMEN; LESIONS; HPV-16; DNA; CARCINOGENICITY AB Cervicovaginal human papillomavirus (HPV) viral load has been purported as a potential marker for the detection of high-grade cervical intraepithelial neoplasia or cancer (>= CIN2). To examine disease association with type-specific viral load for the full-range of anogenital HPV infections, we conducted cross-sectional and prospective analyses of similar to 2,000 HPV-infected women from a 10,000-woman population-based study in Guanacaste, Costa Rica with 7 years of follow-up. Cervical specimens were tested for > 40 HPV types using a MY09/MY11 L1 consensus primer PCR method with type-specific dot blot hybridization and PCR signal intensity as a measure of viral load. A positive association was observed between prevalent >= CIN2 and high viral load compared to low viral load for women with baseline single HPV16 infections (OR = 19.2, 95% CI = 4.4-83.2) and single non-16 carcinogenic infections (OR = 9.2, 95% CI = 2.1-39.9). Inclusion of women with multiple HPV types did not substantially change these associations. In prospective follow-up, only women infected with HPV16 alone (OR = 27.2, 95% = 3.5-213.5) had a strong association between high viral load and incident >= CIN2; non-16 carcinogenic high viral load was not associated with incident >= CIN2 (OR = 0.7, 95% CI = 0.2-1.9). Single noncarcinogenic type viral load was not associated with increased risk of prevalent or incident >= CIN2 (OR = 1.2 and 1.1, respectively). In conclusion, carcinogenic high viral load was associated with prevalent > CIN2; however HPV16 was uniquely associated with incident > CIN2. The extent to which these observations can be translated into clinical practice must be rigorously examined in the context of the method of viral load measurement and the type-specific differences observed for incident > CIN2. (c) 2007 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA. Fdn INCIENSA, San Jose, Costa Rica. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA. RP Gravitt, PE (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6535, Baltimore, MD 21205 USA. EM pgravitt@jhsph.edu FU NCI NIH HHS [N01-CP-21081, CA78527, N01-CP-33061, N01-CP-40542, N01-CP-50535, N01-CP-81023, P50 CA098252, R01 CA078527, U01 CA078527] NR 30 TC 86 Z9 94 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 2007 VL 121 IS 12 BP 2787 EP 2793 DI 10.1002/ijc.23012 PG 7 WC Oncology SC Oncology GA 233RW UT WOS:000251109000030 PM 17722112 ER PT J AU Johnson, MO Charlebois, E Morin, SF Remien, RH Chesney, MA AF Johnson, Mallory O. Charlebois, Edwin Morin, Stephen F. Remien, Robert H. Chesney, Margaret A. CA Natl Inst Mental Hlth Hlthy LPT TI Effects of a behavioral intervention on antiretroviral medication adherence among people living with HIV - The healthy living project randomized controlled study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adherence; antiretroviral therapy compliance; randomized controlled trial ID THERAPY ADHERENCE; VIRAL LOAD; NONADHERENCE; PROTEASE; TRIALS; RESISTANCE; INHIBITORS; EFFICACY; CITIES; WOMEN AB Objective: To examine the effect of a 15-session individually delivered cognitive behavioral intervention on anfiretroviral (ART) medication adherence. Design: A multisite, 2-group, randomized controlled trial. Participants: Two hundred four HIV-infected participants with selfreported ART adherence < 85% from a total of 3818 participants screened were randomized into the trial. Potential participants were recruited for the main trial based on sexual risk criteria in Los Angeles, Milwaukee, New York, and San Francisco. Intervention: The primary outcome of the intervention was a reduction in HIV transmission risk behaviors. Fifteen 90-minute individually delivered sessions were divided into 3 modules: Stress, Coping, and Adjustment; Safer Behaviors; and Health Behaviors, including an emphasis on ART adherence. Controls received no intervention until trial completion. Both groups completed follow-up assessments at 5, 10, 15, 20, and 25 months after randomization. Main Outcome Measure: Self-reported ART adherence as measured by 3-day computerized assessment. Results: A significance difference in rates of reported adherence was observed between intervention and control participants at months 5 and 15, corresponding to the assessments after the Stress, Coping, and Adjustment module (5-month time point) and after the Health Behaviors module (15-month time point). The relative improvements among the intervention group compared with the control group dissipated at follow-up. Conclusions: Cognitive behavioral intervention programs may effectively improve ART adherence, but the effects of intervention may be short-lived. C1 Univ Calif San Francisco, Ctr AIDS Studies, San Francisco, CA 95105 USA. Columbia Univ, New State Psychiat Inst, HIV Ctr Clin & Behav Studies, New York, NY USA. Univ Calif Los Angeles, Ctr Community Hlth, Los Angeles, CA 90024 USA. Med Coll Wisconsin, Ctr AIDS Intervent Res, Milwaukee, WI 53226 USA. NIMH, Bethesda, MD 20892 USA. RP Johnson, MO (reprint author), Univ Calif San Francisco, Ctr AIDS Studies, 50 Beale St,Suite 1300, San Francisco, CA 95105 USA. FU NIMH NIH HHS [U10MH057631, U10MH057636, U10 MH057636, U10 MH057631, U10MH057616, U10MH057615, U10 MH057616, P30 MH043520, U10 MH057615, U10 MH057616-07] NR 24 TC 42 Z9 42 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2007 VL 46 IS 5 BP 574 EP 580 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 236YA UT WOS:000251338200008 PM 18193499 ER PT J AU Waters, L Kambugu, A Tibenderana, H Meya, D John, L Mandalia, S Nabankema, M Namugga, I Quinn, TC Gazzard, B Reynolds, SJ Nelson, M AF Waters, Laura Kambugu, Andrew Tibenderana, Hilda Meya, David John, Laurence Mandalia, Sundhiva Nabankema, Maggie Namugga, Irene Quinn, Thomas C. Gazzard, Brian Reynolds, Steven J. Nelson, Mark TI Evaluation of filter paper transfer of whole-blood and plasma samples for quantifying HIV RNA in subjects on antiretroviral therapy in Uganda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT Annual Conference of the British-HIV-Association CY APR 25-28, 2007 CL Glasgow, SCOTLAND SP British HIV Assoc DE dried blood spot; viral load; developing world; antiretroviral monitoring; virologic ID DRIED BLOOD; LOAD AB Background: Most HIV-infected subjects on antiretroviral therapy (ART) in resource-limited settings do not undergo virologic monitoring. There is an urgent need for cheap, accessible HIV RNA assays for early diagnosis of virologic failure. We investigated filter paper transfer (FPT) of whole blood and plasma as an alternative to standard plasma-based assays for virologic monitoring in Uganda. Methods: Whole blood (n = 306) and plasma (n - 218) from 402 subjects established on ART were spotted onto filter paper and transported to Europe for HIV RNA extraction and quantification. These results were compared to a gold standard plasma assay in Kampala. Results: Of 402 ART-treated subjects, 39 (9.7%) had viremia detectable (> 500 copies/mL) by local methods. Plasma FPT showed excellent agreement with gold standard, whereas whole blood yielded a large number of false-positive viral loads. Conclusions: This is the first study to investigate the use of FPT in ART-treated subjects and demonstrates that it may provide a practical, reliable method for virologic monitoring in resource-poor settings. Plasma FPT was accurate but requires centrifuge; whole blood produced a high number of false-positive results, but these were lowlevel. Whole blood may be sufficiently accurate if higher HIV RNA cut-offs were used to define virologic failure. C1 Chelsea & Wistminster Hosp, St Stephens AIDS Trust, London, England. Makerere Univ, Infect Dis Inst, Kampala, Uganda. NIH, NIAID, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Waters, L (reprint author), St Marys Hosp, London W2 1NY, England. EM laura.waters@btintemet.com NR 7 TC 30 Z9 30 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 15 PY 2007 VL 46 IS 5 BP 590 EP 593 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 236YA UT WOS:000251338200010 PM 18193501 ER PT J AU Shaner, NC Patterson, GH Davidson, MW AF Shaner, Nathan C. Patterson, George H. Davidson, Michael W. TI Advances in fluorescent protein technology SO JOURNAL OF CELL SCIENCE LA English DT Article DE fluorescent proteins; mutagenesis; optical highlighters; photoactivation; photoconversion; photoswitching; live-cell imaging ID TO-RED CONVERSION; MONOMERIC RED; CRYSTAL-STRUCTURE; IMPROVED GREEN; DIRECTED EVOLUTION; STRUCTURAL BASIS; GFP; CELLS; FRET; CYAN AB Current fluorescent protein ( FP) development strategies are focused on fine-tuning the photophysical properties of blue to yellow variants derived from the Aequorea victoria jellyfish green fluorescent protein (GFP) and on the development of monomeric FPs from other organisms that emit in the yellow-orange to far-red regions of the visible light spectrum. Progress toward these goals has been substantial, and near-infrared emitting FPs may loom over the horizon. The latest efforts in jellyfish variants have resulted in new and improved monomeric BFP, CFP, GFP and YFP variants, and the relentless search for a bright, monomeric and fast-maturing red FP has yielded a host of excellent candidates, although none is yet optimal for all applications. Meanwhile, photoactivatable FPs are emerging as a powerful class of probes for intracellular dynamics and, unexpectedly, as useful tools for the development of superresolution microscopy applications. C1 [Shaner, Nathan C.] Salk Inst Biol Studies, La Jolla, CA 92037 USA. [Patterson, George H.] NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. [Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. [Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32310 USA. RP Shaner, NC (reprint author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM shaner@salk.edu; pattersg@mail.nih.gov; davidson@magnet.fsu.edu RI Shaner, Nathan/C-1331-2011 NR 79 TC 431 Z9 445 U1 15 U2 175 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD DEC 15 PY 2007 VL 120 IS 24 BP 4247 EP 4260 DI 10.1242/jcs.005801 PG 14 WC Cell Biology SC Cell Biology GA 249QG UT WOS:000252243300003 PM 18057027 ER PT J AU Kobayashi, T Hearing, VJ AF Kobayashi, Takeshi Hearing, Vincent J. TI Direct interaction of tyrosinase with Tyrp1 to form heterodimeric complexes in vivo SO JOURNAL OF CELL SCIENCE LA English DT Article DE tyrosinase; Tyrp1; heterodimer; melanosome; crosslinking ID OCULOCUTANEOUS ALBINISM; 5,6-DIHYDROXYINDOLE-2-CARBOXYLIC ACID; ENDOPLASMIC-RETICULUM; MELANOGENIC PROTEINS; MAMMALIAN TYROSINASE; OXIDASE ACTIVITY; LOCUS PROTEIN; DHICA OXIDASE; BROWN LOCUS; MELANOCYTES AB Mutations of the critical and rate-limiting melanogenic enzyme tyrosinase (Tyr) result in hypopigmentation of the hair, skin and eyes. Two other related enzymes, Tyrp1 and Dct, catalyze distinct post-Tyr reactions in melanin biosynthesis. Tyr, Tyrp1 and Dct have been proposed to interact with and stabilize each other in multi-enzyme complexes, and in vitro, Tyr activity is more stable in the presence of Tyrp1 and/or Dct. We recently reported that Tyr is degraded more quickly in mutant Tyrp1 mouse melanocytes than in wild-type Tyrp1 melanocytes, and that decreased stability of Tyr can be partly rescued by infection with wild-type Tyrp1. Although interactions between Tyr and Tyrp1 have been demonstrated in vitro, there is no direct evidence for Tyr interaction with Tyrp1 in vivo. In this study, we use in vivo chemical crosslinking to stabilize the association of Tyr with other cellular proteins. Western blot analysis revealed that Tyrp1, but not Dct, associates with Tyr in murine melanocytes in vivo, and more specifically, in melanosomes. Two-dimensional SDS-PAGE analysis detected heterodimeric species of Tyr and Tyrp1. Taken together, these data demonstrate that Tyrp1 interacts directly with Tyr in vivo, which may regulate the stability and trafficking of melanogenic enzymes and thus pigment synthesis. C1 [Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Kobayashi, Takeshi] Nagoya Univ, Sch Med, Dept Physiol, Nagoya, Aichi 4668550, Japan. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM hearingv@nih.gov FU Intramural NIH HHS NR 46 TC 31 Z9 33 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD DEC 15 PY 2007 VL 120 IS 24 BP 4261 EP 4268 DI 10.1242/jcs.017913 PG 8 WC Cell Biology SC Cell Biology GA 249QG UT WOS:000252243300004 PM 18042623 ER PT J AU Singh, NJ Cox, M Schwartz, RH AF Singh, Nevil J. Cox, Maureen Schwartz, Ronald H. TI TLR ligands differentially modulate T cell responses to acute and chronic antigen presentation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-II; DENDRITIC CELLS; IN-VIVO; ADAPTIVE TOLERANCE; CLONAL EXPANSION; IMMUNE-RESPONSES; PLASMA-MEMBRANE; PROTEIN ANTIGEN; SELF-ANTIGENS; CUTTING EDGE AB The outcome of peripheral T cell activation is thought to be largely determined by the context in which the cognate Ag is initially presented. In this framework, microbial products that can activate APCs via TLRs are considered critical in converting an otherwise tolerogenic context to an immunogenic one. We examine this idea using a model system where naive T cells are stimulated in the periphery by a persistent self Ag. The addition of multiple TLR ligands to this context, acutely or chronically, failed to significantly alter the tolerogenic phenotype in the responding T cells. This contrasts with the ability of such adjuvants to improve T cell responses to soluble peptide immunizations. We reconcile this difference by revealing a hitherto poorly appreciated property of TLR ligands, which extends the duration of soluble Ag presentation in vivo by an additional two to three days. Finally, we could replace the requirement for TLR-mediated APC activation in soluble-Ag-induced T cell expansion and differentiation, by maintaining the Ag depot in vivo using repeated immunizations. These data suggest a novel process by which TLR ligands modulate T cell responses to acute Ags, without disrupting the induction of tolerance to persistent self Ags. C1 [Singh, Nevil J.; Schwartz, Ronald H.] NIAID, NIH, Cellular & Mol Immunol Lab, Bethesda, MD 20892 USA. [Cox, Maureen] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Singh, NJ (reprint author), NIAID, NIH, Cellular & Mol Immunol Lab, Bldg 4,Room 111,4 Ctr Dr, Bethesda, MD 20892 USA. EM nsingh@naiaid.nih.gov OI Cox, Maureen/0000-0001-8030-3340 FU Intramural NIH HHS NR 70 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2007 VL 179 IS 12 BP 7999 EP 8008 PG 10 WC Immunology SC Immunology GA 240LV UT WOS:000251590000002 PM 18056339 ER PT J AU Vallbracht, S Jessen, B Mrusek, S Enders, A Collins, PL Ehl, S Krempl, CD AF Vallbracht, Simone Jessen, Birthe Mrusek, Sonja Enders, Anselm Collins, Peter L. Ehl, Stephan Krempl, Christine D. TI Influence of a single viral epitope on T cell response and disease after infection of mice with respiratory syncytial virus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; VACCINIA VIRUS; M2 PROTEIN; CTL RESPONSE; CLEAR VIRUS; PEPTIDE; IMMUNODOMINANCE; RESISTANCE; LUNG; GLYCOPROTEIN AB CTL are important for virus clearance but also contribute to immunopathology after the infection of BALB/c mice with respiratory syncytial virus (RSV). The pulmonary immune response to RSV is dominated by a CTL population directed against the CTL epitope M2-1 82-90. Infection with a virus carrying an M2-1 N89A mutation introduced by reverse genetics failed to activate this immunodominant CTL population, leading to a significant decrease in the overall antiviral CTL response. There was no compensatory increase in responses to the mutated epitope, to the subdominant epitope F 85-93, or to yet undefined minor epitopes in the N or the P protein. However, there was some increase in the response to the subdominant epitope M2-1 127-135, which is located in the same protein and presented by the same H-2K(d) MHC molecule. Infection with the mutant virus reversed the oligoclonality of the T cell response elicited by the wild-type virus. These changes in the pattern and composition of the antiviral CTL response only slightly impaired virus clearance but significantly reduced RSV-induced weight loss. These data illustrate how T cell epitope mutations can influence the virus-host relationship and determine disease after an acute respiratory virus infection. C1 [Vallbracht, Simone; Jessen, Birthe; Mrusek, Sonja; Enders, Anselm; Ehl, Stephan] Univ Hosp Freiburg, Ctr Pediat & Adolescent Med, Freiburg, Germany. [Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Krempl, Christine D.] Univ Hosp Freiburg, Dept Virol, Inst Med Microbiol & Hyg, Freiburg, Germany. RP Ehl, S (reprint author), Zentrum Kinderheilkunde & Jugendmed, Mathildenstr 1, Freiburg, Germany. EM stephan.ehl@uniklinik-freiburg.de RI Enders, Anselm/B-1165-2011; Krempl, Christine/O-2081-2015 OI Enders, Anselm/0000-0001-5933-6463; FU Intramural NIH HHS NR 42 TC 13 Z9 14 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2007 VL 179 IS 12 BP 8264 EP 8273 PG 10 WC Immunology SC Immunology GA 240LV UT WOS:000251590000033 PM 18056370 ER PT J AU Martin, JE Pierson, TC Hubka, S Rucker, S Gordon, IJ Enama, ME Andrews, CA Xu, Q Davis, BS Nason, MC Fay, MP Koup, RA Roederer, M Bailer, RT Gomez, PL Mascola, JR Chang, GJJ Nabel, GJ Graham, BS AF Martin, Julie E. Pierson, Theodore C. Hubka, Sarah Rucker, Steve Gordon, Ingelise J. Enama, Mary E. Andrews, Charla A. Xu, Qing Davis, Brent S. Nason, Martha C. Fay, Michael P. Koup, Richard A. Roederer, Mario Bailer, Robert T. Gomez, Phillip L. Mascola, John R. Chang, Gwong-Jen J. Nabel, Gary J. Graham, Barney S. CA Vaccine Res Ctr 302 Study Team TI A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the American-Society-of-Gene-Therapy CY MAY 31-JUN 04, 2006 CL Baltimore, MD SP Amer Soc Gene Therapy ID CANDIDATE VACCINE; INFECTION; ENCEPHALITIS; PROTECTS; EPIDEMIOLOGY; FEVER; PALMS AB Background. West Nile virus (WNV) is a mosquitoborne flavivirus that can cause severe meningitis and encephalitis in infected individuals. We report the safety and immunogenicity of a WNV DNA vaccine in its first phase 1 human study. Methods. A single-plasmid DNA vaccine encoding the premembrane and the envelope glycoproteins of the NY99 strain of WNV was evaluated in an open-label study in 15 healthy adults. Twelve subjects completed the 3-dose vaccination schedule, and all subjects completed 32 weeks of evaluation for safety and immunogenicity. The development of a vaccine-induced immune response was assessed by enzyme-linked immunosorbant assay, neutralization assays, intracelluar cytokine staining, and enzyme-linked immunospot assay. Results. The vaccine was safe and well tolerated, with no significant adverse events. Vaccine-induced T cell and antibody responses were detected in the majority of subjects. Neutralizing antibody to WNV was detected in all subjects who completed the 3-dose vaccination schedule, at levels shown to be protective in studies of horses, an incidental natural host for WNV. Conclusions. Further assessment of this DNA platform for human immunization against WNV is warranted. C1 [Martin, Julie E.; Hubka, Sarah; Rucker, Steve; Gordon, Ingelise J.; Enama, Mary E.; Andrews, Charla A.; Nason, Martha C.; Fay, Michael P.; Koup, Richard A.; Roederer, Mario; Bailer, Robert T.; Gomez, Phillip L.; Mascola, John R.; Nabel, Gary J.; Graham, Barney S.] NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Pierson, Theodore C.; Xu, Qing] NIAID, NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD USA. [Davis, Brent S.; Chang, Gwong-Jen J.] Ctr Dis Control & Prevent, Natl Ctr Zoonot Vector Borne & Enter Dis, Div Vector Borne Infect Dis, Arboviral Dis Branch, Ft Collins, CO USA. RP Graham, BS (reprint author), NIAID, NIH, Vaccine Res Ctr, 40 Convent Dr, Bethesda, MD 20892 USA. EM bgraham@nih.gov RI Roederer, Mario/G-1887-2011; OI Fay, Michael P./0000-0002-8643-9625 FU Intramural NIH HHS [Z99 AI999999] NR 32 TC 100 Z9 108 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2007 VL 196 IS 12 BP 1732 EP 1740 DI 10.1086/523650 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 245GH UT WOS:000251922600005 PM 18190252 ER PT J AU Permar, SR Rao, SS Sun, Y Bao, S Buzby, AP Kang, HH Letvin, NL AF Permar, Sallie R. Rao, Srinivas S. Sun, Yue Bao, Saran Buzby, Adam P. Kang, Helen H. Letvin, Norman L. TI Clinical measles after measles virus challenge in simian immunodeficiency virus-infected measles virus-vaccinated rhesus monkeys SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies/Society-of-Pediatric-Research CY APR 29-MAY 02, 2006 CL San Francisco, CA SP Pediat Acad Soc, Soc Pediat Res ID GIANT-CELL PNEUMONIA; POLYMERASE CHAIN-REACTION; CD8(+) LYMPHOCYTES; VIRAL REPLICATION; ATYPICAL MEASLES; CHILDREN; ANTIBODY; IMMUNIZATION; MACAQUES; TYPE-1 AB Understanding the impact of human immunodeficiency virus (HIV) infection on the clinical manifestations and kinetics of measles virus (MV) replication in MV-vaccinated and unvaccinated individuals is important for developing successful vaccine strategies for measles eradication. To model the pathogenesis of MV infection in MV-vaccinated and unvaccinated individuals infected with HIV, previously vaccinated and unvaccinated rhesus monkeys infected with simian immunodeficiency virus (SIV) were challenged with MV and monitored for clinical, virologic, and immunologic sequelae of infection. The magnitude and duration of MV viremia were unchanged by SIV infection. Nevertheless, clinical manifestations of MV infection were altered in animals with significant CD4(+) T lymphocyte loss. Importantly, 2 of the 3 SIV-infected monkeys with high titers of vaccine-induced MV-neutralizing antibody developed clinical evidence of MV infection. Thus, in this experimental animal model, a high-titer vaccine-induced MV-neutralizing antibody response does not protect against clinical manifestations of measles in the setting of a chronic acquired immunodeficiency syndrome virus infection. C1 [Permar, Sallie R.; Sun, Yue; Buzby, Adam P.; Kang, Helen H.; Letvin, Norman L.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. [Permar, Sallie R.] Childrens Hosp, Harvard Med Sch, Dept Med, Boston, MA USA. [Rao, Srinivas S.; Bao, Saran] Vaccine Res Ctr, NIH, Lab Anim Med, Bethesda, MD USA. RP Letvin, NL (reprint author), Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, 330 Brookline Ave, Boston, MA 02115 USA. EM nletvin@bidmc.harvard.edu FU Intramural NIH HHS; NIAID NIH HHS [AI 20729] NR 43 TC 3 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2007 VL 196 IS 12 BP 1784 EP 1793 DI 10.1086/522967 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 245GH UT WOS:000251922600012 PM 18190259 ER PT J AU Henriquez, VM Schulz, GM Bielamowicz, S Ludlow, CL AF Henriquez, Victor M. Schulz, Geralyn M. Bielamowicz, Steven Ludlow, Christy L. TI Laryngeal reflex responses are not modulated during human voice and respiratory tasks SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID THYROARYTENOID MUSCLE RESPONSES; AIR-PRESSURE STIMULATION; LONG-LATENCY RESPONSES; NERVE-STIMULATION; AWAKE HUMANS; SPASMODIC DYSPHONIA; STRETCH REFLEXES; SUPPRESSION; AFFERENTS; MOVEMENT AB The laryngeal adductor response (LAR) is a protective reflex that prevents aspiration and can be elicited either by electrical stimulation of afferents in the superior laryngeal nerve (SLN) or by deflection of mechanoreceptors in the laryngeal mucosa. We hypothesized that because this reflex is life-sustaining, laryngeal muscle responses to sensory stimuli would not be suppressed during volitional laryngeal tasks when compared to quiet respiration. Unilateral electrical superior laryngeal nerve stimulation was used to elicit early (R1) and late (R2) responses in the ipsilateral thyroarytenoid muscle in 10 healthy subjects. The baseline levels of muscle activity before stimulation, R1 and R2 response occurrence and the integrals of responses were measured during each task: quiet inspiration, prolonged vowels, humming, forced inhalation and effort closure. We tested whether R1 response integrals during tasks were equal to either: (1) baseline muscle activity during the task added to the response integral at rest; (2) the response integral at rest minus the baseline muscle activity during the task; or (3) the response integral at rest. R1 response occurrence was not altered by task from rest while fewer R2 responses occurred only during effort closure and humming compared to rest. Because the R1 response integrals did not change from rest, task increases in motor neuron firing did not alter the LAR. These findings demonstrate that laryngeal motor neuron responses to sensory inputs are not gated during volitional tasks confirming the robust life-sustaining protective mechanisms provided by this airway reflex. C1 [Henriquez, Victor M.; Schulz, Geralyn M.; Bielamowicz, Steven; Ludlow, Christy L.] NINDS, Laryngeal & Speech Sect, NIH, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), NINDS, Laryngeal & Speech Sect, NIH, Bldg 10,Room 5D 38,10 Ctr Dr MSC 1416, Bethesda, MD 20892 USA. EM ludlowc@ninds.nih.gov OI Schulz, Geralyn/0000-0003-3831-8105; Ludlow, Christy/0000-0002-2015-6171 FU Intramural NIH HHS [Z01 NS002980-09] NR 33 TC 8 Z9 8 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 15 PY 2007 VL 585 IS 3 BP 779 EP 789 DI 10.1113/jphysiol.2007.143438 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 243AF UT WOS:000251766600019 PM 17962327 ER PT J AU Friedly, J Deyo, RA Chan, L AF Friedly, Janna Deyo, Richard A. Chan, Leighton TI Increases in lumbosacral injections in the medicare population - Response SO SPINE LA English DT Letter ID EPIDURAL STEROID INJECTION; CONTROLLED-TRIAL C1 [Friedly, Janna] Univ Washington, Ctr Clin Effectiveness Costs & Outcomes, Dept Rehabil Med, Seattle, WA 98195 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Portland, OR USA. [Chan, Leighton] Natl Inst Hlth, Dept Rehabil Med, Bethesda, MD USA. RP Friedly, J (reprint author), Univ Washington, Ctr Clin Effectiveness Costs & Outcomes, Dept Rehabil Med, Seattle, WA 98195 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD DEC 15 PY 2007 VL 32 IS 26 BP 3091 EP 3092 PG 2 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 242AL UT WOS:000251696800036 ER PT J AU Friedly, J Deyo, RA Chan, L AF Friedly, Janna Deyo, Richard A. Chan, Leighton TI Increases in lumbosacral injections in the medicare population - Response SO SPINE LA English DT Letter ID CONTROLLED-TRIAL C1 [Friedly, Janna] Univ Washington, Ctr Clin Effectiveness Costs & Outcomes, Dept Rehabil Med, Seattle, WA 98195 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Portland, OR USA. [Chan, Leighton] Natl Inst Hlth, Dept Rehabil Med, Bethesda, MD USA. RP Friedly, J (reprint author), Univ Washington, Ctr Clin Effectiveness Costs & Outcomes, Dept Rehabil Med, Seattle, WA 98195 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD DEC 15 PY 2007 VL 32 IS 26 BP 3092 EP 3093 PG 2 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 242AL UT WOS:000251696800038 ER PT J AU Di Iorio, A Abate, M Guralnik, JM Bandinelli, S Cecchi, F Cherubini, A Corsonello, A Foschini, N Guglielmi, M Lauretani, F Volpato, S Abate, G Ferrucci, L AF Di Iorio, Angelo Abate, Michele Guralnik, Jack M. Bandinelli, Stefania Cecchi, Francesca Cherubini, Antonio Corsonello, Andrea Foschini, Nunzia Guglielmi, Marianna Lauretani, Fulvio Volpato, Stefano Abate, Giuseppe Ferrucci, Luigi TI From chronic low back pain to disability, a multifactorial mediated pathway - The InCHIANTI Study SO SPINE LA English DT Article DE back pain; physical performance; disability; elderly; InCHIANTI study ID DWELLING OLDER PERSONS; PHYSICAL FUNCTION; PSYCHOLOGICAL-FACTORS; COMMUNITY SAMPLE; PERFORMANCE; HEALTH; WOMEN; ADULTS; EPIDEMIOLOGY; PREVALENCE AB Study Design. Clinicoepidemiologic study in the Chianti area (Tuscany, Italy). Objective. To evaluate whether performance measures of lower extremity function confounds the association of low back pain (LBP) with self-report disability in specific basic and instrumental activities of daily living (IADLs). Summary of Background Data. LBP is high prevalent in older population and has a negative impact on functional status. Studies on the pathway leading from LBP to disability are limited and often the role played by important confounders is not considered. Methods. A total of 956 InCHIANTI study participants aged 65 and older able to complete performance based tests of lower extremity function were include in this analysis. LBP was defined as a self report of back pain "quite often-almost every day" in the past 12 months. Lower extremity function was evaluated administering the Short Physical Performance Battery. In addition, participants were asked to walk on a 7-m course and collect an object from the ground. Depressive symptoms (CES-D score), trunk flexion-extension range of motion, and hip-knee-foot pain were also considered in the pathway from LBP to disability. Results. Compared with participants who did not report LBP, those with LBP were more likely to report difficulty in performing most activities of daily living. LBP was also associated with disability in the activities of bathing, doing the laundry, performing heavy household chores, cutting toenails, shopping, and carrying a shopping bag. The association between LBP and disability in selected ADLs and IADLs was no longer statistical significant, aster adjustment for performance in lower extremity function, with exception of the activity of "carrying a shopping bag". Conclusion. The cross-sectional association between LBP and self-reported disability in specific tasks is modulated by performance measures. Specific performance based tests that explore the functional consequences of LBP may help design specific interventions of disability prevention and treatment in patients with LBP. C1 [Di Iorio, Angelo; Foschini, Nunzia; Guglielmi, Marianna; Abate, Giuseppe] Univ G DAnnunzio, Lab Clin Epidemiol, Dept Med Sci Aging, Geriatr Unit, I-66013 Chieti, Italy. [Abate, Michele] Univ G DAnnunzio, Post Grad Sch Phys Med & Rehabil, Dept Med & Sci Aging, I-66013 Chieti, Italy. [Guralnik, Jack M.] NIH, Natl Inst Aging, Lab Epidemiol, Bethesda, MD 20892 USA. [Bandinelli, Stefania] Geriatr Rehabil Unit, Azienda Sanitaria Firenze, Florence, Italy. [Cecchi, Francesca] Inst Recovery & Care Sci Character, Fdn Don Carlo Gnocchi, Florence, Italy. [Cherubini, Antonio] Univ Perugia, Inst Gerontol & Geriatr, Perugia, Italy. [Corsonello, Andrea] Ist Nazl Ric & Cura Anziani, Geriatr Unit, Cosenza, Italy. [Lauretani, Fulvio] Tuscany Reg Hlth Agcy, Lab Clin Epidemiol, Florence, Italy. [Volpato, Stefano] Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. [Ferrucci, Luigi] NIH, Natl Inst Aging, Longitudinal Studies Sect, Baltimore, MD USA. RP Di Iorio, A (reprint author), Univ G DAnnunzio, Lab Clin Epidemiol, Dept Med Sci Aging, Geriatr Unit, Via dei Vestini 5, I-66013 Chieti, Italy. EM a.diiorio@unich.it RI Corsonello, Andrea/A-5637-2013; VOLPATO, STEFANO/H-2977-2014 OI Corsonello, Andrea/0000-0002-7276-3256; VOLPATO, STEFANO/0000-0003-4335-6034 FU Intramural NIH HHS [Z99 AG999999] NR 25 TC 20 Z9 20 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD DEC 15 PY 2007 VL 32 IS 26 BP E809 EP E815 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 242AL UT WOS:000251696800003 PM 18091475 ER PT J AU Woods, CG Kosyk, O Bradford, BU Ross, PK Burns, AM Cunningham, ML Qu, PP Ibrahim, JG Rusyn, I AF Woods, Courtney G. Kosyk, Oksana Bradford, Blair U. Ross, Pamela K. Burns, Amanda M. Cunningham, Michael L. Qu, Pingping Ibrahim, Joseph G. Rusyn, Ivan TI Time course investigation of PPAR alpha- and Kupffer cell-dependent effects of WY-14,643 in mouse liver using microarray gene expression SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE peroxisome proliferators; PPAR alpha; kupffer cells; toxicogenomics; microarrays ID ACTIVATED RECEPTOR-ALPHA; TUMOR-NECROSIS-FACTOR; PEROXISOME PROLIFERATOR; IN-VIVO; NADPH OXIDASE; HEPATOCYTE PROLIFERATION; NONGENOTOXIC CARCINOGEN; NUCLEAR RECEPTORS; OXIDATIVE STRESS; RAT HEPATOCYTES AB Administration of peroxisome proliferators to rodents causes proliferation of peroxisomes, induction of beta-oxidation enzymes, hepatocellular hypertrophy and hyperplasia, with chronic exposure ultimately leading to hepatocellular carcinomas. Many responses associated with peroxisome proliferators are nuclear receptor-mediated events involving peroxisome proliferators-activated receptor alpha (PPAR alpha). A role for nuclear receptor-independent events has also been shown, with evidence of Kupffer cell-mediated free radical production, presumably through NAPDH oxidase, induction of redox-sensitive transcription factors involved in cytokine production and cytokine-mediated cell replication following acute treatment with peroxisome proliferators in rodents. Recent studies have demonstrated, by using p47(phox)-null mice which are deficient in NADPH oxidase, that this enzyme is not related to the phenotypic events caused by prolonged administration of peroxisome proliferators. In an effort to determine the timing of the transition from Kupffer cell-to PPAR alpha-dependent modulation of peroxisome proliferator effects, gene expression was assessed in liver from Ppar alpha-null, p47(phox)-null and corresponding wild-type mice following treatment with 4-chloro-6-(2,3-xylidino)-pyrimidynylthioacetic acid (WY-14,643) for 8 h, 24 h, 72 h, 1 week or 4 weeks. WY-14,643-induced gene expression in p47(phox)-null mouse liver differed substantially from wild-type mice at acute doses and striking differences in baseline expression of immune related genes were evident. Pathway mapping of genes that respond to WY-14,643 in a time-and dose-dependent manner demonstrates suppression of immune response, cell death and signal transduction and promotion of lipid metabolism, cell cycle and DNA repair. Furthermore, these pathways were largely dependent on PPAR alpha, not NADPH oxidase demonstrating a temporal shift in response to peroxisome proliferators. Overall, this study shows that NADPH oxidase-dependent events, while detectable following acute treatment, are transient. To the contrary, a strong PPAR alpha-specific gene signature was evident in mice that were continually exposed to WY-14,643. (c) 2007 Elsevier Inc. All rights reserved. C1 Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA. Univ N Carolina, Dept Environm Sci & Engn, Michael Hooker Res Ctr 0031, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Michael Hooker Res Ctr 0031, CB 7431, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016 FU NIEHS NIH HHS [P42 ES005948-160010, P42 ES005948, P42 ES005948-150010, R01 ES012686, R01 ES012686-04, R01 ES015241, R01 ES015241-02, U19 ES011391, U19 ES011391-05] NR 52 TC 12 Z9 12 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 15 PY 2007 VL 225 IS 3 BP 267 EP 277 DI 10.1016/j.taap.2007.08.028 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 239RI UT WOS:000251535000005 PM 17950772 ER PT J AU Koonin, EV Makarova, KS Elkins, JG AF Koonin, Eugene V. Makarova, Kira S. Elkins, James G. TI Orthologs of the small RPB8 subunit of the eukaryotic RNA polymerases are conserved in hyperthermophilic Crenarchaeota and "Korarchaeota" SO BIOLOGY DIRECT LA English DT Article ID TRANSCRIPTION; SULFOLOBUS; SEQUENCES AB Although most of the key components of the transcription apparatus, and in particular, RNA polymerase ( RNAP) subunits, are conserved between archaea and eukaryotes, no archaeal homologs of the small RPB8 subunit of eukaryotic RNAP have been detected. We report that orthologs of RPB8 are encoded in all sequenced genomes of hyperthermophilic Crenarchaeota and a recently sequenced "korarchaeal" genome, but not in Euryarchaeota or the mesophilic crenarchaeon Cenarchaeum symbiosum. These findings suggest that all 12 core subunits of eukaryotic RNAPs were already present in the last common ancestor of the extant archaea. C1 [Koonin, Eugene V.; Makarova, Kira S.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Elkins, James G.] Oak Ridge Natl Lab, Biosci Div, Microbila Ecol & Physiol Grp, Oak Ridge, TN 37831 USA. RP Koonin, EV (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov; makarova@ncbi.nlm.nih.gov; elkinsjg@ornl.gov RI Elkins, James/A-6199-2011 OI Elkins, James/0000-0002-8052-5688 FU Intramural NIH HHS NR 19 TC 27 Z9 27 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD DEC 14 PY 2007 VL 2 AR 38 DI 10.1186/1745-6150-2-38 PG 5 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 274QO UT WOS:000254016100001 PM 18081935 ER PT J AU Munch, J Rucker, E Standker, L Adermann, K Goffinet, C Schindler, M Wildum, S Chinnadurai, R Rajan, D Specht, A Gimenez-Gallego, G Sanchez, PC Fowler, DM Koulov, A Kelly, JW Mothes, W Grivel, JC Margolis, L Keppler, OT Forssmann, WG Kirchhoff, F AF Muench, Jan Ruecker, Elke Staendker, Ludger Adermann, Knut Goffinet, Christine Schindler, Michael Wildum, Steffen Chinnadurai, Raghavan Rajan, Devi Specht, Anke Gimenez-Gallego, Guillermo Cuevas Sanchez, Pedro Fowler, Douglas M. Koulov, Atanas Kelly, Jeffery W. Mothes, Walther Grivel, Jean-Charles Margolis, Leonid Keppler, Oliver T. Forssmann, Wolf-Georg Kirchhoff, Frank TI Semen-derived amyloid fibrils drastically enhance HIV infection SO CELL LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SEXUAL TRANSMISSION; ACID-PHOSPHATASE; VIRAL LOAD; IN-VITRO; PROTEIN; CELLS; MEN; MODEL; QUANTIFICATION AB Sexual intercourse is the major route of HIV transmission. To identify endogenous factors that affect the efficiency of sexual viral transmission, we screened a complex peptide/protein library derived from human semen. We show that naturally occurring fragments of the abundant semen marker prostatic acidic phosphatase (PAP) form amyloid fibrils. These fibrils, termed Semen-derived Enhancer of Virus Infection (SEVI), capture HIV virions and promote their attachment to target cells, thereby enhancing the infectious virus titer by several orders of magnitude. Physiological concentrations of SEVI amplified HIV infection of T cells, macrophages, ex vivo human tonsillar tissues, and transgenic rats in vivo, as well as trans-HIV infection of T cells by dendritic or epithelial cells. Amyloidogenic PAP fragments are abundant in seminal fluid and boost semen-mediated enhancement of HIV infection. Thus, they may play an important role in sexual transmission of HIV and could represent new targets for its prevention. C1 [Staendker, Ludger; Adermann, Knut; Forssmann, Wolf-Georg] IPF PharmaCeut GmbH, D-30625 Hannover, Germany. [Muench, Jan; Ruecker, Elke; Schindler, Michael; Wildum, Steffen; Chinnadurai, Raghavan; Rajan, Devi; Specht, Anke; Kirchhoff, Frank] Univ Clin Ulm, Inst Virol, D-89081 Ulm, Germany. [Staendker, Ludger; Adermann, Knut; Forssmann, Wolf-Georg] Hannover Med Sch, Ctr Pharmacol, D-30625 Hannover, Germany. [Adermann, Knut] VIRO Pharmaceut GmbH & Co KG, D-30625 Hannover, Germany. [Goffinet, Christine; Keppler, Oliver T.] Univ Heidelberg, Dept Virol, D-69120 Heidelberg, Germany. [Gimenez-Gallego, Guillermo] CSIC, Ctr Invest Biol, Madrid 28040, Spain. [Cuevas Sanchez, Pedro] Hosp Ramon & Cajal, E-28034 Madrid, Spain. [Fowler, Douglas M.; Koulov, Atanas; Kelly, Jeffery W.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Fowler, Douglas M.; Koulov, Atanas; Kelly, Jeffery W.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Mothes, Walther] Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06536 USA. [Grivel, Jean-Charles; Margolis, Leonid] NICHHD, Bethesda, MD 20892 USA. RP Forssmann, WG (reprint author), IPF PharmaCeut GmbH, D-30625 Hannover, Germany. EM wg.forssman@pharis.de; frank.kirchhoff@uniklinik-ulm.de RI Schindler, Michael/C-1647-2015; OI Schindler, Michael/0000-0001-8989-5813; Koulov, Atanas/0000-0003-0262-7002 FU Intramural NIH HHS; NIAID NIH HHS [1R01AI067057-01A2] NR 44 TC 279 Z9 289 U1 3 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD DEC 14 PY 2007 VL 131 IS 6 BP 1059 EP 1071 DI 10.1016/j.cell.2007.10.014 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249GU UT WOS:000252217100015 PM 18083097 ER PT J AU Harrigan, JA Piotrowski, J Di Noto, L Levine, RL Bohr, VA AF Harrigan, Jeanine A. Piotrowski, Jason Di Noto, Luca Levine, Rodney L. Bohr, Vilhelm A. TI Metal-catalyzed oxidation of the Werner syndrome protein causes loss of catalytic activities and impaired protein-protein interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MIXED-FUNCTION OXIDATION; DNA-DAMAGE; BINDING-SITE; WRN PROTEIN; MECHANISM; HELICASE; COMPLEX; IRON; AGE; KU AB Metal-catalyzed oxidation reactions target amino acids in the metal binding pocket of proteins. Such oxidation reactions generally result in either preferential degradation of the protein or accumulation of a catalytically inactive pool of protein with age. Consistently, levels of oxidized proteins have been shown to increase with age. The segmental, progeroid disorder Werner syndrome results from loss of the Werner syndrome protein (WRN). WRN is a member of the RecQ family of DNA helicases and possesses exonuclease and ATP-dependent helicase activities. Furthermore, each of the helicase and exonuclease domains of WRN contains a metal binding pocket. In this report we examined for metal-catalyzed oxidation of WRN in the presence of iron or copper. We found that WRN was oxidized in vitro by iron but not by copper. Iron-mediated oxidation resulted in the inhibition of both WRN helicase and exonuclease activities. Oxidation of WRN also inhibited binding to several known protein partners. In addition, we did not observe degradation of oxidized WRN by the 20 S proteasome in vitro. Finally, exposure of cells to hydrogen peroxide resulted in oxidation of WRN in vivo. Therefore, our results demonstrate that WRN undergoes metal-catalyzed oxidation in the presence of iron, and iron-mediated oxidation of WRN likely results in the accumulation of a catalytically inactive form of the protein, which may contribute to age-related phenotypes. C1 NIH, NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. NIH, NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Bohr, VA (reprint author), NIH, NIA, Lab Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov RI Levine, Rodney/D-9885-2011 FU Intramural NIH HHS NR 40 TC 10 Z9 10 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2007 VL 282 IS 50 BP 36403 EP 36411 DI 10.1074/jbc.M706107200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238OY UT WOS:000251458300032 PM 17911100 ER PT J AU Berdiev, BK Cormet-Boyaka, E Tousson, A Qadri, YJ Oosterveld-Hut, HMJ Hong, JS Gonzales, PA Fuller, CM Sorscher, EJ Lukacs, GL Benos, DJ AF Berdiev, Bakhrom K. Cormet-Boyaka, Estelle Tousson, Albert Qadri, Yawar J. Oosterveld-Hut, Henderika M. J. Hong, Jeong S. Gonzales, Patricia A. Fuller, Cathy M. Sorscher, Eric J. Lukacs, Gergely L. Benos, Dale J. TI Molecular proximity of cystic fibrosis transmembrane conductance regulator and epithelial sodium channel assessed by fluorescence resonance energy transfer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SENSITIVE NA+ CHANNELS; CFTR CHLORIDE CHANNEL; SURFACE EXPRESSION; LUNG-DISEASE; GAMMA-ENAC; PROTEIN; GENE; IDENTIFICATION; SUBUNITS; INHIBITION AB We present the evidence for a direct physical association of cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC), two major ion channels implicated in the pathophysiology of cystic fibrosis, a devastating inherited disease. We employed fluorescence resonance energy transfer, a distance-dependent imaging technique with capability to detect molecular complexes with near angstrom resolution, to estimate the proximity of CFTR and ENaC, an essential variable for possible physical interaction to occur. Fluorescence resonance energy transfer studies were complemented with a classic biochemical approach: coimmunoprecipitation. Our results place CFTR and ENaC within reach of each other, suggestive of a direct interaction between these two proteins. C1 Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Univ Alabama, High Resolut Imaging Facil, Birmingham, AL 35294 USA. Univ Alabama, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35294 USA. Ohio State Univ, Davis Heart & Lung Res Inst, Div Pulm & Crit Care & Sleep Med, Columbus, OH 43210 USA. Lambert Instruments, NL-9313 TH Leutingewolde, Netherlands. NIH, NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. Univ Toronto, Hosp Sick Children, Res Inst, Dept Lab Med & Pathobiol Program Cell & Lung Biol, Toronto, ON M5G 1X8, Canada. RP Berdiev, BK (reprint author), Univ Alabama, Dept Cell Biol, 1918 Univ Blvd,MCLM 725, Birmingham, AL 35294 USA. EM berdiev@uab.edu RI Fuller, Cathy/B-4046-2011; Cormet-Boyaka, Estelle/H-5624-2011; OI Qadri, Yawar/0000-0003-2138-4018; Lukacs, Gergely/0000-0003-0900-0675 FU NIDDK NIH HHS [2R01-DK37206-15, P50 DK53090-05, R01-DK075302] NR 49 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2007 VL 282 IS 50 BP 36481 EP 36488 DI 10.1074/jbc.M708089200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238OY UT WOS:000251458300040 PM 17913705 ER PT J AU Lee, KS Raymond, LD Schoen, B Raymond, GJ Kett, L Moore, RA Johnson, LM Taubner, L Speare, JO Onwubiko, HA Baron, GS Caughey, WS Caughey, B AF Lee, Kil S. Raymond, Lynne D. Schoen, Brianna Raymond, Gregory J. Kett, Lauren Moore, Roger A. Johnson, Lisa M. Taubner, Lara Speare, Jonathan O. Onwubiko, Henry A. Baron, Gerald S. Caughey, Winslow S. Caughey, Byron TI Hemin interactions and alterations of the subcellular localization of prion protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELLULAR PRION; CASPASE-3 ACTIVATION; NEUROBLASTOMA-CELLS; OCTAREPEAT REGION; SULFATED GLYCANS; OXIDATIVE STRESS; PLASMA-MEMBRANE; CULTURED-CELLS; ENDOCYTOSIS; DISEASE AB Hemin (iron protoporphyrin IX) is a crucial component of many physiological processes acting either as a prosthetic group or as an intracellular messenger. Some unnatural, synthetic porphyrins have potent anti-scrapie activity and can interact with normal prion protein (PrPC). These observations raised the possibility that hemin, as a natural porphyrin, is a physiological ligand for PrPC. Accordingly, we evaluated PrPC interactions with hemin. When hemin (3-10 mu M) was added to the medium of cultured cells, clusters of PrPC formed on the cell surface, and the detergent solubility of PrPC decreased. The addition of hemin also induced PrPC internalization and turnover. The ability of hemin to bind directly to PrPC was demonstrated by hemin-agarose affinity chromatography and UV-visible spectroscopy. Multiple hemin molecules bound primarily to the N-terminal third of PrPC, with reduced binding to PrPC lacking residues 34-94. These hemin-PrPC interactions suggest that PrPC may participate in hemin homeostasis, sensing, and/or uptake and that hemin might affect PrPC functions. C1 NIAID, NIH, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM bcaughey@nih.gov RI Lee, Kil/D-3678-2012 FU Intramural NIH HHS NR 63 TC 29 Z9 31 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2007 VL 282 IS 50 BP 36525 EP 36533 DI 10.1074/jbc.M705620200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238OY UT WOS:000251458300045 PM 17925394 ER PT J AU Mans, BJ Calvo, E Ribeiro, JMC Andersen, JF AF Mans, Ben J. Calvo, Eric Ribeiro, Jose M. C. Andersen, John F. TI The crystal structure of D7r4, a salivary biogenic amine-binding protein from the malaria mosquito anopheles gambiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADULT FEMALE MOSQUITO; HISTAMINE-BINDING; PHEROMONE-BINDING; AEDES-AEGYPTI; DENSITY MODIFICATION; RHODNIUS-PROLIXUS; NMR STRUCTURE; GLAND; SIALOME; CLONING AB The D7-related (D7r) proteins of the malaria vector Anopheles gambiae have been shown to bind the biogenic amines serotonin, norepinephrine, and histamine with high affinity. One member of the group (D7r1 or hamadarin) has also been shown to have an anticoagulant/antikinin activity. To understand the mechanistic details of its antihemostatic/anti-inflammatory effects, we have determined the crystal structure of one member of this group, D7r4, along with the structures of ligand complexes with serotonin, tryptamine, histamine, and norepinephrine. The D7 fold consists of an arrangement of eight alpha-helices stabilized by three disulfide bonds. The structure is similar to those of the arthropod odorant-binding proteins, a relationship that had been predicted based on sequence comparisons. Although odorant-binding proteins commonly have six alpha-helices, D7r4 has eight, resulting in significantly different positioning and structure of the ligand binding pocket. The pocket itself is lined by hydrophobic side chains along with polar and charged groups oriented to form hydrogen bonds with the aliphatic amino group and with groups on the aromatic portions of the ligands. These structures, along with accompanying mutagenesis studies, have allowed us to identify critical residues for biogenic amine binding and to predict which members of the large D7 protein family found in blood-feeding nematocerous Diptera will function as biogenic amine-binding proteins. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Andersen, JF (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rm 2E32B,Twinbrook 3 Bldg,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM jandersen@niaid.nih.gov OI Mans, Ben/0000-0002-0177-0029; Calvo, Eric/0000-0001-7880-2730; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS NR 42 TC 31 Z9 31 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2007 VL 282 IS 50 BP 36626 EP 36633 DI 10.1074/jbc.M706410200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238OY UT WOS:000251458300055 PM 17928288 ER PT J AU List, K Currie, B Scharschmidt, TC Szabo, R Shireman, J Molinolo, A Cravatt, BF Segre, J Bugge, TH AF List, Karin Currie, Brooke Scharschmidt, Tiffany C. Szabo, Roman Shireman, Jessica Molinolo, Alfredo Cravatt, Benjamin F. Segre, Julia Bugge, Thomas H. TI Autosomal ichthyosis with hypotrichosis syndrome displays low matriptase proteolytic activity and is phenocopied in ST14 hypomorphic mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSMEMBRANE SERINE-PROTEASE; EPIDERMAL BARRIER FUNCTION; NETHERTON-SYNDROME; FILAGGRIN; SKIN; DIFFERENTIATION; CANCER; PROFILAGGRIN; DEGRADATION; INITIATION AB Human autosomal recessive ichthyosis with hypotrichosis (ARIH) is an inherited disorder recently linked to homozygosity for a point mutation in the ST14 gene that causes a G827R mutation in the matriptase serine protease domain (G216 in chymotrypsin numbering). Here we show that human G827R matriptase has strongly reduced proteolytic activity toward small molecule substrates, as well as toward its candidate epidermal target, prostasin. To further investigate the possible contribution of low matriptase activity to ARIH, we generated an ST14 hypomorphic mouse strain that displays a 100-fold reduction in epidermal matriptase mRNA levels. Interestingly, unlike ST14 null mice, ST14 hypomorphic mice were viable and fertile but displayed a spectrum of abnormalities that strikingly resembled ARIH. Thus, ST14 hypomorphic mice developed hyperproliferative and retention ichthyosis with impaired desquamation, hypotrichosis with brittle, thin, uneven, and sparse hair, and tooth defects. Biochemical analysis of ST14 hypomorphic epidermis revealed reduced prostasin proteolytic activation and profilaggrin proteolytic processing, compatible with a primary role of matriptase in this process. This work strongly indicates that reduced activity of a matriptase-prostasin proteolytic cascade is the etiological origin of human ARIH and provides an important mouse model for the exploration of matriptase function in ARIH, as well as multiple other physiological and pathological processes. C1 NIDCR, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Res Scholars Program, Chevy Chase, MD 20815 USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Bugge, TH (reprint author), NIDCR, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Rm 211, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov OI Scharschmidt, Tiffany/0000-0001-5517-089X FU Intramural NIH HHS NR 47 TC 56 Z9 57 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2007 VL 282 IS 50 BP 36714 EP 36723 DI 10.1074/jbc.M705521200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238OY UT WOS:000251458300064 PM 17940283 ER PT J AU Dagdug, L Berezhkovskii, AM Makhnovskii, YA Zitserman, VY AF Dagdug, Leonardo Berezhkovskii, Alexander M. Makhnovskii, Yurii A. Zitserman, Vladimir Yu. TI Transient diffusion in a tube with dead ends SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID BRAIN EXTRACELLULAR-SPACE; VENTRICULAR MYOCARDIUM; POROUS-MEDIA; TORTUOSITY; MICRODOMAINS; CHANNEL; WATER AB A particle diffusing in a tube with dead ends, from time to time enters a dead end, spends some time in the dead end, and then comes back to the tube. As a result, the particle spends in the tube only a part of the entire observation time that leads to slowdown of its diffusion along the tube. We study the transient diffusion in a tube with periodic identical dead ends formed by cavities of volume V(cav) connected to the tube by cylindrical channels of length L and radius a, which is assumed to be much smaller than the tube radius R and the distance l between neighboring dead ends. Assuming that the particle initial position is uniformly distributed over the tube, we analyze the monotonic decrease of the particle diffusion coefficient D(t) from its initial value D(0)=D, which characterizes diffusion in the tube without dead ends, to its asymptotic long-time value D(infinity)=D(eff)< D. We derive an expression for the Laplace transform of D(t), denoted by D(s), where s is the Laplace parameter. Although the expression is too complicated to be inverted analytically, we use it to find the relaxation time of the process as a function of the geometric parameters of the system mentioned above. To check the accuracy of our results, we ran Brownian dynamics simulations and found the mean squared displacement of the particle as a function of time by averaging over 5x10(4) realizations of the particle trajectory. The time-dependent mean squared displacement found in simulations is compared with that obtained by numerically inverting the Laplace transform of the mean squared displacement predicted by the theory, which is given by 2D(s)/s. Comparison shows excellent agreement between the two time dependences that support the approximations used when developing the theory. (c) 2007 American Institute of Physics. C1 [Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico. [Berezhkovskii, Alexander M.] Ctr Informat Technol, NIH, Div Computat Biosci, Math & Stat Computing Lab, Bethesda, MD 20892 USA. [Makhnovskii, Yurii A.] Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Moscow 119991, Russia. [Zitserman, Vladimir Yu.] Russian Acad Sci, Joint Inst High Temperatures, Moscow 125412, Russia. RP Dagdug, L (reprint author), Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Apartado Postal 55-534, Mexico City 09340, DF, Mexico. EM ldagdug@helix.nih.gov RI Makhnovskii, Yurii/B-1223-2014 OI Makhnovskii, Yurii/0000-0002-1517-536X NR 21 TC 28 Z9 28 U1 0 U2 4 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 14 PY 2007 VL 127 IS 22 AR 224712 DI 10.1063/1.2805068 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 241TO UT WOS:000251678900042 PM 18081419 ER PT J AU Sonenberg, N Hinnebusch, AG AF Sonenberg, Nahum Hinnebusch, Alan G. TI New modes of translational control in development, behavior, and disease SO MOLECULAR CELL LA English DT Article ID MESSENGER-RNA TRANSLATION; LOCAL PROTEIN-SYNTHESIS; DIET-INDUCED OBESITY; RIBOSOME ENTRY SITE; VIRUS IRES RNA; INITIATION-FACTOR; EUKARYOTIC TRANSLATION; BINDING-PROTEIN; INHIBITS TRANSLATION; SYNAPTIC PLASTICITY AB Over the last 10 years, the field of translational control has been enriched by atomic resolution structures of ribosomal complexes and factors in different functional states, and increased in sophistication by wedding genetics, reconstituted systems, and structural biology to elucidate basic reactions and mRNA-specific control mechanisms. New regulatory principles have emerged, including repression by micro-RNAs (miRNAs) and mRNA sequestration in cytoplasmic granules, and the field has extended its reach into development, brain function, and human disease. Here we seek to highlight some of the exciting developments of the last decade from the perspectives of our own approaches and expertise; accordingly, many highly noteworthy achievements could not be mentioned and we refer interested readers to the numerous excellent reviews cited below. C1 [Sonenberg, Nahum] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. [Sonenberg, Nahum] McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada. [Hinnebusch, Alan G.] NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Sonenberg, N (reprint author), McGill Univ, Dept Biochem, 3655 Drummond St, Montreal, PQ H3G 1Y6, Canada. EM nahum.sonenberg@mcgill.ca NR 79 TC 122 Z9 122 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 14 PY 2007 VL 28 IS 5 BP 721 EP 729 DI 10.1016/j.molcel.2007.11.018 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 245HP UT WOS:000251926000005 PM 18082597 ER PT J AU Song, SH Hou, CH Dean, A AF Song, Sang-Hyun Hou, Chunhui Dean, Ann TI A positive role for NLI/Ldb1 in long-range beta-globin locus control region function SO MOLECULAR CELL LA English DT Article ID DOMAIN INTERACTOR NLI; WING MARGIN ENHANCER; BINDING-PROTEIN LDB1; RNA-POLYMERASE-II; C-KIT EXPRESSION; ACTIVITY IN-VIVO; ERYTHROID-DIFFERENTIATION; CHROMATIN-STRUCTURE; GENE-EXPRESSION; HOMEODOMAIN PROTEINS AB Long-range interactions between distant regulatory elements, such as enhancers, and their target genes underlie the specificity of gene expression in many developmentally regulated gene families. NLI/Ldb1, a widely expressed nuclear factor, is a potential mediator of long-range interactions. Here, we show that NLI/ Ldb1 and erythroid-binding partners GATA-1/ SCL/LMO2 bind in vivo to the beta-globin locus control region (LCR). The C-terminal LIM interaction domain of NLI is required for formation of the complex on chromatin. Loss of the LIM domain converts NLI into a dominant-negative inhibitor of globin gene expression, and knockdown of NLI by using shRNA results in failure to activate beta-globin expression. Kinetic studies reveal that the NLI/GATA-1/SCL/LMO2 complex is detected at the beta-globin promoter coincident with RNA Pol II recruitment, beta-globin transcription, and chromatin loop formation during erythroid differentiation, providing evidence that NLI facilitates long-range gene activation. C1 [Song, Sang-Hyun; Hou, Chunhui; Dean, Ann] NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dean, A (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM anndean@helix.nih.gov RI Hou, Chunhui/A-6596-2009 FU Intramural NIH HHS [Z01 DK015508-19] NR 55 TC 122 Z9 127 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 14 PY 2007 VL 28 IS 5 BP 810 EP 822 DI 10.1016/j.molcel.2007.09.025 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 245HP UT WOS:000251926000014 PM 18082606 ER PT J AU Madon, T Hofman, KJ Kupfer, L Glass, RI AF Madon, Temina Hofman, Karen J. Kupfer, Linda Glass, Roger I. TI Public health - Implementation science SO SCIENCE LA English DT Editorial Material ID MALARIA; TRANSMISSION; CIRCUMCISION; COVERAGE C1 NIH, Div Adv Sci & Policy Anal, John E Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Hofman, KJ (reprint author), NIH, Div Adv Sci & Policy Anal, John E Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM hofmank@mail.nih.gov OI Kupfer, Linda/0000-0002-6886-6818 NR 19 TC 157 Z9 160 U1 2 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD DEC 14 PY 2007 VL 318 IS 5857 BP 1728 EP 1729 DI 10.1126/science/1150009 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 240VR UT WOS:000251616800022 PM 18079386 ER PT J AU Ryan, JF Baxevanis, AD AF Ryan, Joseph F. Baxevanis, Andreas D. TI Hox, Wnt, and the evolution of the primary body axis: insights from the early-divergent phyla SO BIOLOGY DIRECT LA English DT Review ID 18S RIBOSOMAL-RNA; PHYLOGENETIC POSITION; HOMEOBOX GENES; SEA-ANEMONE; TRICHOPLAX-ADHAERENS; MITOCHONDRIAL GENOME; BILATERAL SYMMETRY; METAZOAN EVOLUTION; ANIMAL DEVELOPMENT; MOLECULAR EVIDENCE AB The subkingdom Bilateria encompasses the overwhelming majority of animals, including all but four early-branching phyla: Porifera, Ctenophora, Placozoa, and Cnidaria. On average, these early-branching phyla have fewer cell types, tissues, and organs, and are considered to be significantly less specialized along their primary body axis. As such, they present an attractive outgroup from which to investigate how evolutionary changes in the genetic toolkit may have contributed to the emergence of the complex animal body plans of the Bilateria. This review offers an up-to-date glimpse of genome-scale comparisons between bilaterians and these early-diverging taxa. Specifically, we examine these data in the context of how they may explain the evolutionary development of primary body axes and axial symmetry across the Metazoa. Next, we re-evaluate the validity and evolutionary genomic relevance of the zootype hypothesis, which defines an animal by a specific spatial pattern of gene expression. Finally, we extend the hypothesis that Wnt genes may be the earliest primary body axis patterning mechanism by suggesting that Hox genes were co-opted into this patterning network prior to the last common ancestor of cnidarians and bilaterians. Open peer review: Reviewed by Pierre Pontarotti, Gaspar Jekely, and L Aravind. For the full reviews, please go to the Reviewers' comments section. C1 [Ryan, Joseph F.; Baxevanis, Andreas D.] NIH, Genome Technol Branch, NHGRI, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), NIH, Genome Technol Branch, NHGRI, Bethesda, MD 20892 USA. EM jfryan@mail.nih.gov; andy@mail.nih.gov FU Intramural NIH HHS NR 99 TC 27 Z9 28 U1 1 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD DEC 13 PY 2007 VL 2 AR 37 DI 10.1186/1745-6150-2-37 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 259FI UT WOS:000252924100001 PM 18078518 ER PT J AU Nolan, KA Zhao, H Faulder, PF Frenkel, AD Timson, DJ Siegel, D Ross, D Burke, TR Stratford, IJ Bryce, RA AF Nolan, Karen A. Zhao, He Faulder, Paul F. Frenkel, A. David Timson, David J. Siegel, David Ross, David Burke, Terrence R., Jr. Stratford, Ian J. Bryce, Richard A. TI Coumarin-based inhibitors of human NAD(P)H : quinone oxidoreductase-1. Identification, structure-activity, off-target effects and in vitro human pancreatic cancer toxicity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MECHANISM-BASED INHIBITOR; QUINONE OXIDOREDUCTASE-1; FORCE-FIELD; NQO1; DOCKING; GROWTH; CELLS; NAD(P)H-QUINONE-OXIDOREDUCTASE-1; CHEMOPROTECTION; DEGRADATION AB The enzyme human NAD(P)H quinone oxidoreductase-1 (NQO1), which is overexpressed in several types of tumor cell, is considered a design target for cancer therapeutics. We identify new coumarin-based competitive inhibitors of NQO1, one of which is nanomolar. Using computational docking and molecular dynamics, we obtain insights into the structural basis of inhibition. Selected inhibitors were then assessed for off-target effects associated with dicoumarol and were found to have differing effects on superoxide formation and mitochondrial respiration. A comparison of NQO1 inhibition and off-target effects for dicoumarol and its derivatives suggests that the ability of dicoumarol to kill cancer cells is independent of NQO1 inhibition, that cellular superoxide production by dicoumarol does not seem linked to NQO1 inhibition but may be related to mitochondrial decoupling, and that superoxide does not appear to be a major determinant of cytotoxicity. Implications are discussed for NQO1 inhibition as an anticancer drug design target and superoxide generation as the dicoumarol-mediated mechanism of cytotoxicity. C1 Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PT, Lancs, England. NCI, Med Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Queens Univ Belfast, Ctr Med Biol, Sch Biol Sci, Belfast BT9 7BL, Antrim, North Ireland. Univ Colorado, Sch Pharm, Dept Pharmaceut Sci, Denver, CO 80220 USA. Univ Colorado, Sch Pharm, Ctr Canc, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80220 USA. RP Stratford, IJ (reprint author), Univ Manchester, Sch Pharm & Pharmaceut Sci, Oxford Rd, Manchester M13 9PT, Lancs, England. EM Ian.Stratford@manchester.ac.uk; Richard.Bryce@manchester.ac.uk RI Burke, Terrence/N-2601-2014; Bryce, Richard/F-9955-2015; OI Bryce, Richard/0000-0002-8145-2345; stratford, ian/0000-0002-5222-4765; Timson, David/0000-0002-0985-8818 FU Intramural NIH HHS; Medical Research Council [G0500366] NR 41 TC 34 Z9 36 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 13 PY 2007 VL 50 IS 25 BP 6316 EP 6325 DI 10.1021/jm070472p PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 239LD UT WOS:000251518900006 PM 17999461 ER PT J AU Metaferia, BB Fetterolf, BJ Shazad-Ul-Hussan, S Moravec, M Smith, JA Ray, S Gutierrez-Lugo, MT Bewley, CA AF Metaferia, Belhu B. Fetterolf, Brandon J. Shazad-ul-Hussan, Syed Moravec, Matthew Smith, Jeremy A. Ray, Satyajit Gutierrez-Lugo, Maria-Teresa Bewley, Carole A. TI Synthesis of natural product-inspired inhibitors of Mycobacterium tuberculosis mycothiol-associated enzymes: The first inhibitors of GlcNAc-Ins deacetylase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID S-CONJUGATE AMIDASE; CRYSTAL-STRUCTURE; BIOSYNTHESIS; EXPRESSION; DOCKING; PATHWAY; ANALOGS; ERDMAN; THIOLS; GROWTH AB Synthesis and evaluation of a chemical library of inhibitors of the mycothiol biosynthesis enzyme GlcNAc-Ins deacetylase (MshB) and the mycothiol-dependent detoxification enzyme mycothiol-S-conjugate amidase (MCA) from Mycobacterium tuberculosis are reported. The library was biased to include structural features of a group of natural products previously shown to competitively inhibit MCA. Molecular docking studies that reproducibly placed the inhibitors in the active site of the enzyme MshB reveal the mode of binding and are consistent with observed biological activity. C1 NIDDKD, Bioorgan Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDKD, Bioorgan Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov FU Intramural NIH HHS NR 35 TC 32 Z9 36 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 13 PY 2007 VL 50 IS 25 BP 6326 EP 6336 DI 10.1021/jm070669h PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 239LD UT WOS:000251518900007 PM 18020307 ER PT J AU Fishelovitch, D Hazan, C Hirao, H Wolfson, HJ Nussinov, R Shaik, S AF Fishelovitch, Dan Hazan, Carina Hirao, Hajime Wolfson, Haim J. Nussinov, Ruth Shaik, Sason TI QM/MM study of the active species of the human cytochrome p450 3A4, and the influence thereof of the multiple substrate binding SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID CHLOROPEROXIDASE COMPOUND-I; ELECTRON-PARAMAGNETIC-RESONANCE; HEME-CONTAINING OXYGENASES; HUMAN LIVER-MICROSOMES; KINETIC CHARACTERIZATION; HORSERADISH-PEROXIDASE; REACTIVE INTERMEDIATE; ALPHA-NAPHTHOFLAVONE; COOPERATIVE BINDING; ELUSIVE OXIDANT AB Cytochrome P450 3A4 is involved in the metabolism of 50% of all swallowed drugs. The enzyme functions by means of a high-valent iron-oxo species, called compound I (Cpd I), which is formed after entrance of the substrate to the active site. We explored the features of Cpd I using hybrid quantum mechanic at/molecular mechanical calculations on various models that are either substrate-free or containing one and two molecules Z of diazepam as a substrate. Mossbauer parameters of Cpd I were computed. Our major finding shows that without the substrate, Cpd I tends to elongate its Fe-S bond, localize the radical on the sulfur, and form hydrogen bonds with A305 and T309, which may hypothetically lead to Cpd I consumption by H-abstraction. However, the positioning of diazepam close to Cpd I, as enforced by the effector molecule, was found to strengthen the NH center dot center dot center dot S interactions of the conserved 1443 and G444 residues with the proximal cysteinate ligand. These interactions are known to stabilize the Fe-S bond, and as such, the presence of the substrate leads to a shorter Fe-S bond and it prevents the localization of the radical on the sulfur. This diazepam-Cpd I stabilization was manifested in the 1 WOE conformer. The effector substrate did not influence Cpd I directly but rather by positioning the active substrate close to Cpd I, thus displacing the hydrogen bonds with A305 and T309, and thereby giving preference to substrate oxidation. It is hypothesized that these effects on Cpd I, promoted by the restrained substrate, may be behind the special metabolic behavior observed in cases of multiple substrate binding (also called cooperative binding). This restraint constitutes a mechanism whereby substrates stabilize Cpd I sufficiently long to affect monooxygenation by P450s at the expense of Cpd I destruction by the protein residues. C1 Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel. Hebrew Univ Jerusalem, Lise Meitner Minerva Ctr Computat Quantum Chem, IL-91904 Jerusalem, Israel. Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. NCI, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. RP Shaik, S (reprint author), Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. EM sason@yfaat.ch.huji.ac.il RI Wolfson, Haim/A-1837-2011; Hirao, Hajime/B-7030-2011 OI Hirao, Hajime/0000-0002-8239-3471 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400, N01 CO012400]; NIAID NIH HHS [1UC1AI067231] NR 72 TC 26 Z9 26 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 13 PY 2007 VL 111 IS 49 BP 13822 EP 13832 DI 10.1021/jp076401j PG 11 WC Chemistry, Physical SC Chemistry GA 239KV UT WOS:000251518100020 PM 18020326 ER PT J AU Matthews, AGW Kuo, AJ Ramon-Maiques, S Han, SM Champagne, KS Ivanov, D Gallardo, M Carney, D Cheung, P Ciccone, DN Walter, KL Utz, PJ Shi, Y Kutateladze, TG Yang, W Gozani, O Oettinger, MA AF Matthews, Adam G. W. Kuo, Alex J. Ramon-Maiques, Santiago Han, Sunmi Champagne, Karen S. Ivanov, Dmitri Gallardo, Mercedes Carney, Dylan Cheung, Peggie Ciccone, David N. Walter, Kay L. Utz, Paul J. Shi, Yang Kutateladze, Tatiana G. Yang, Wei Gozani, Or Oettinger, Marjorie A. TI RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination SO NATURE LA English DT Article ID C-TERMINUS; B-CELL; GENE REARRANGEMENT; PLANT HOMEODOMAIN; PRE-B; METHYLATION; BINDING; TRANSPOSITION; TRANSCRIPTION; ACTIVATION AB Nuclear processes such as transcription, DNA replication and recombination are dynamically regulated by chromatin structure. Eukaryotic transcription is known to be regulated by chromatin-associated proteins containing conserved protein domains that specifically recognize distinct covalent post- translational modifications on histones. However, it has been unclear whether similar mechanisms are involved in mammalian DNA recombination. Here we show that RAG2 - an essential component of the RAG1/2 V(D)J recombinase, which mediates antigen- receptor gene assembly(1) - contains a plant homeodomain ( PHD) finger that specifically recognizes histone H3 trimethylated at lysine 4 ( H3K4me3). The high- resolution crystal structure of the mouse RAG2 PHD finger bound to H3K4me3 reveals the molecular basis of H3K4me3- recognition by RAG2. Mutations that abrogate RAG2's recognition of H3K4me3 severely impair V( D) J recombination in vivo. Reducing the level of H3K4me3 similarly leads to a decrease in V(D)J recombination in vivo. Notably, a conserved tryptophan residue ( W453) that constitutes a key structural component of the K4me3- binding surface and is essential for RAG2's recognition of H3K4me3 is mutated in patients with immunodeficiency syndromes. Together, our results identify a new function for histone methylation in mammalian DNA recombination. Furthermore, our results provide the first evidence indicating that disrupting the read- out of histone modifications can cause an inherited human disease. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Aurora, CO 80045 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ogozani@stanford.edu; oettinger@frodo.mgh.harvard.edu RI Ivanov, Dmitri/B-4600-2011; Yang, Wei/D-4926-2011; OI Yang, Wei/0000-0002-3591-2195; Glass, Karen/0000-0002-2761-733X FU NIAID NIH HHS [P30 AI060354]; NIGMS NIH HHS [R01 GM048026-12, R01 GM048026] NR 40 TC 286 Z9 292 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 13 PY 2007 VL 450 IS 7172 BP 1106 EP U18 DI 10.1038/nature06431 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 240HY UT WOS:000251579900092 PM 18033247 ER PT J AU Remmers, EF Plenge, RM Gregersen, PK AF Remmers, Elaine F. Plenge, Robert M. Gregersen, Peter K. TI Rheumatoid arthritis, systemic lupus erythematosus, and STAT4 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID AUTOIMMUNE-DISEASES C1 NIAMSD, Bethesda, MD 20892 USA. Broad Inst, Cambridge, MA 02142 USA. Feinstein Inst Med Res, Manhasset, NY 11030 USA. RP Remmers, EF (reprint author), NIAMSD, Bethesda, MD 20892 USA. EM peterg@nshs.edu NR 2 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 13 PY 2007 VL 357 IS 24 BP 2518 EP 2518 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 240CK UT WOS:000251564400023 ER PT J AU Lee, JH Yedavalli, VRK Jeang, KT AF Lee, Jia Hai Yedavalli, Venkat R. K. Jeang, Kuan-Teh TI Activation of HIV-I expression and replication by cGMP dependent protein kinase type I-beta (PKGI beta) SO RETROVIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; FACTOR-KAPPA-B; NONDIVIDING CELLS; CYCLIC-GMP; TRANSCRIPTION; TAT; PHOSPHORYLATION; PROMOTER; INFECTION AB The effect of cGMP (cyclic GMP) dependent protein kinase 1-beta (PKGI-beta) and cGMP analogues on transcriptional activity and replication of human immunodeficiency virus type I (HIV-I) was investigated. Transfection of PKGI beta expression plasmid increased expression from an HIV-I LTR-reporter as well as from an infectious HIV-I molecular clone, pNL4-3. Treatment of HIV-I AD8-infected monocyte derived macrophages (MDMs) with cGMP agonists and cGMP antagonists caused respectively increased and decreased virus replication. These findings provide evidence that cGMP and PKG serve to regulate HIV-I infection in human cells. C1 [Lee, Jia Hai; Yedavalli, Venkat R. K.; Jeang, Kuan-Teh] NIAID, NIH, Mol Microbiol Lab, Mol Virol Sect, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, NIH, Mol Microbiol Lab, Mol Virol Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jiahai@yahoo.com; vyedavalli@mail.nih.gov; kjeang@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 24 TC 4 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD DEC 13 PY 2007 VL 4 AR 91 DI 10.1186/1742-4690-4-91 PG 6 WC Virology SC Virology GA 260EU UT WOS:000252994400002 PM 18078512 ER PT J AU Blackinton, JG Anuret, A Beilina, A Olson, L Cookson, MR Galter, D AF Blackinton, Jeff G. Anuret, Anna Beilina, Alexandra Olson, Lars Cookson, Mark R. Galter, Dagmar TI Expression of PINK1 mRNA in human and rodent brain and in Parkinson's disease SO BRAIN RESEARCH LA English DT Article DE in situ hybridization; neurodegeneration; PARK6 ID MOUSE-BRAIN; RECESSIVE PARKINSONISM; ALPHA-SYNUCLEIN; LOCALIZATION; PROTEIN; RAT; MUTATIONS; DYSFUNCTION; ABSENCE; LRRK2 AB Mutations in PINK1 (PTEN-induced putative kinase 1) are causal for early onset recessive parkinsonism in humans, characterized by damage to the nigrostriatal system. In situ hybridization studies in rodent brains have suggested a predominantly neuronal expression of PINK1 mRNA but immunocytochemistry of human brain tissue has shown PINK1-like immunoreactivity in both neurons and glia. In this study, we assessed the comparative distribution of PINK1 mRNA in human, rat and mouse brain. We observe that in humans PINK1 message is expressed in neurons with very little to no signal in glia and confirms similar findings in rodent tissue. Highest levels of expression were observed in hippocampus, substantia nigra and cerebellar Purkinje cells. We also show that PINK1 mRNA expression is similar in nigral neurons from neurologically normal controls and sporadic Parkinson's disease cases. (C) 2007 Elsevier B.V. All rights reserved. C1 [Blackinton, Jeff G.; Anuret, Anna; Olson, Lars; Galter, Dagmar] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. [Blackinton, Jeff G.; Beilina, Alexandra; Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Galter, D (reprint author), Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden. EM Dagmar.Galter@ki.se RI Galter, Dagmar/C-4826-2011 OI Galter, Dagmar/0000-0001-6485-6244 FU Intramural NIH HHS; NIMH NIH HHS [MH/NS31862] NR 25 TC 27 Z9 27 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 12 PY 2007 VL 1184 BP 10 EP 16 DI 10.1016/j.brainres.2007.09.056 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 247RF UT WOS:000252096600002 PM 17950257 ER PT J AU Schweinberger, SR Kaufmann, JM Moratti, S Keil, A Burton, AM AF Schweinberger, Stefan R. Kaufmann, Juergen M. Moratti, Stephan Keil, Andreas Burton, A. Mike TI Brain responses to repetitions of human and animal faces, inverted faces, and objects - An MEG study SO BRAIN RESEARCH LA English DT Article DE face perception; specificity; MEG; M170; M250r; repetition ID PERSONALLY FAMILIAR FACES; HUMAN EXTRASTRIATE CORTEX; EVENT-RELATED POTENTIALS; LONG-TERM-MEMORY; VISUAL-CORTEX; NEURAL SYSTEM; RECOGNITION; PERCEPTION; MECHANISMS; LOCALIZATION AB Recent studies have identified a prominent face-selective ERP response to immediate repetitions of faces similar to 250 ms (N250r) which was strongly attenuated or eliminated for control stimuli (Schweinberger, Huddy, and Burton 2004, NeuroReport, 15, 1501-1505). In the present study we used a 148-channel whole head neuromagnetometer to investigate event-related magnetic fields (ERMFs) elicited by repetitions of exemplars of human faces, inverted human faces, primate faces, and car fronts. Participants counted rare pictures of butterflies interspersed in a series of pairs of one of these categories. The second stimulus of each pair could either be a repetition or a non-repetition of the first stimulus. We observed prominent M100 (90-140 ms) and M170 (140-220 ms) responses. Both M100 and M170 were insensitive to repetition and showed little differences between stimulus categories, except for a slight increase and delay of M170 to inverted faces. By contrast, we observed a repetition-sensitive M250r response (220-330 ms). This M250r was larger for upright human and primate faces when compared to both inverted human faces and cars, a finding that was specific for right hemispheric sensors. Source localization suggested different generators for M170 and M250r in occipitotemporal and fusiform areas, respectively. These findings suggest that repetition-sensitive brain activity similar to 250 ms reflects the transient activation of object representations, with largest responses for upright faces, in the right hemisphere. (c) 2007 Elsevier B.V. All rights reserved. C1 [Schweinberger, Stefan R.; Kaufmann, Juergen M.] Univ Jena, Dept Gen Psychol, D-07743 Jena, Germany. [Moratti, Stephan; Keil, Andreas] Univ Konstanz, Dept Psychol, D-7750 Constance, Germany. [Schweinberger, Stefan R.; Kaufmann, Juergen M.; Burton, A. Mike] Univ Glasgow, Dept Psychol, Glasgow G12 8QQ, Lanark, Scotland. [Moratti, Stephan] Univ Complutense Madrid, Ctr Magnetoencephalog, Madrid, Spain. [Keil, Andreas] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. [Keil, Andreas] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL 32611 USA. RP Schweinberger, SR (reprint author), Univ Jena, Dept Gen Psychol, Steiger,3 Haus 1, D-07743 Jena, Germany. EM stefan.schweinberger@uni-jena.de RI Burton, A. Mike/A-9491-2008; Schweinberger, Stefan/A-1860-2009; Keil, Andreas/F-9427-2011; OI Burton, A. Mike/0000-0002-2035-2084; Keil, Andreas/0000-0002-4064-1924; Moratti, Stephan/0000-0003-0824-8759 NR 54 TC 42 Z9 42 U1 4 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 12 PY 2007 VL 1184 BP 226 EP 233 DI 10.1016/j.brainres.2007.09.079 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 247RF UT WOS:000252096600026 PM 17976538 ER PT J AU Bian, QM Shi, T Chuang, DM Qian, YI AF Bian, Qingming Shi, Tao Chuang, De-Maw Qian, Yanning TI Lithium reduces ischemia-induced hippocampal CA1 damage and behavioral deficits in gerbils SO BRAIN RESEARCH LA English DT Article DE lithium; neuroprotection; global ischernia; habituation; working memory; gerbil ID CEREBRAL-ISCHEMIA; GLUTAMATE EXCITOTOXICITY; TRANSIENT ISCHEMIA; PROTECTS NEURONS; CORTICAL-NEURONS; RAT; NEUROPROTECTION; BRAIN; INDUCTION; MODEL AB Lithium is a major drug used for the treatment of bipolar mood disorder and has recently been shown to have neuroprotective properties. in this study we investigated the neuroprotective effects of lithium in gerbils subjected to global cerebral ischemia, an animal model of stroke. The ischemia-induced exploratory behavior changes, measured by open field testing, were largely suppressed by lithium treatment for 7 days prior to ischemic onset. Similarly, memory impairments, measured by T-maze testing, were prevented by lithium pretreatment. This is believed to be the first report of lithium-induced protection against hyperactivity in a novel open field and memory impairment in a gerbil model of global ischemia. These behavioral benefits were associated with an increase in viable cells as measured by hernatoxylin and eosin staining and a decrease in apoptotic TUNEL-positive cells in the CA1 hippocampal area of ischemic gerbils. Moreover, the lithium-induced neuroprotection was accompanied by down-regulation of pro-apoptotic p53 in the CA1 but up-regulation of anti-apoptotic Bcl-2 and heat shock protein 70 (HSP70) in the ischemic brain. These results underscore the ability of lithium to improve functional behavioral outcome in gerbil and rodent cerebral ischemic models and further indicate the potential therapeutic use of lithium in certain human stroke conditions. (c) 2007 Elsevier B.V. All rights reserved. C1 [Bian, Qingming; Shi, Tao; Qian, Yanning] First Affiliated Hosp Nanjing Med Univ, Dept Anesthesiol, Nanjing 210029, Peoples R China. [Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Qian, YI (reprint author), First Affiliated Hosp Nanjing Med Univ, Dept Anesthesiol, Nanjing 210029, Peoples R China. EM yanning_qian@yahoo.com.cn FU Intramural NIH HHS NR 35 TC 48 Z9 55 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 12 PY 2007 VL 1184 BP 270 EP 276 DI 10.1016/j.brainres.2007.09.054 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 247RF UT WOS:000252096600031 PM 18028886 ER PT J AU Waguespack, J Salles, FT Kachar, B Ricci, AJ AF Waguespack, Jessica Salles, Felipe T. Kachar, Bechara Ricci, Anthony J. TI Stepwise morphological and functional maturation of mechanotransduction in rat outer hair cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE outer hair cells; mechanoelectrical transduction; auditory; adaptation; myosin Ic; myosin IIIa; stereocilium links ID MECHANOELECTRICAL TRANSDUCTION; FAST ADAPTATION; MYOSIN IIIA; TIP LINKS; STEREOCILIA; BUNDLES; LOCALIZATION; RECEPTORS; CALCIUM; CHANNEL AB Inner ear mechanosensory hair cells convert mechanical vibrations into electrical signals via the coordinated interaction of multiple proteins precisely positioned within the sensory hair bundle. Present work identifies the time course for the acquisition and maturation of mechanoelectric transduction (MET) in rat cochlea outer hair cells maintained in organotypic cultures. A spatiotemporal developmental progression was observed morphologically and functionally with basal cochlea maturation preceding apical cochlea by 2-3 d in all measured properties. The fraction of mechanosensitive cells increased rapidly, with a midpoint at postnatal day 0 for basal cells, and correlated with myosin IIIa immunoreactivity. MET current magnitude increased over several days. Adaptation lagged the onset of transduction by a day and matured more slowly, overlapping but preceding the rise in myosin Ic immunoreactivity. Less than similar to 25% of myosin Ic expression was required for the mature adaptation response, suggesting multiple roles for this protein in hair bundle function. Directional sensitivity, lacking in immature responses, developed rapidly and correlated with the pruning of radial links and an increase in tenting of stereociliary tips. Morphological and electrophysiological data support a hypothesis in which key elements arrive independently at the site of MET, with a mature response occurring as membrane tension increases, likely by the increased tensioning of the tip link with the onset of adaptation. Organotypic cultures developed normal, tonotopically specific, MET response properties, suggesting that maturation was not influenced significantly by external factors such as innervation, endolymph, normal mechanical stimulation, or an intact organ of Corti. C1 [Ricci, Anthony J.] Stanford Univ, Dept Otolaryngol, Stanford, CA 94305 USA. [Waguespack, Jessica; Ricci, Anthony J.] Louisiana State Hlth Sci Ctr, Ctr Neurosci, New Orleans, LA 70112 USA. [Waguespack, Jessica; Salles, Felipe T.; Kachar, Bechara; Ricci, Anthony J.] Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Ricci, AJ (reprint author), Stanford Univ, Dept Otolaryngol, 801 Welch Rd, Stanford, CA 94305 USA. EM aricci@stanford.edu RI Salles, Felipe/H-7544-2013 FU Intramural NIH HHS; NIDCD NIH HHS [R01 DC003896, DC03896] NR 41 TC 69 Z9 69 U1 0 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 12 PY 2007 VL 27 IS 50 BP 13890 EP 13902 DI 10.1523/JNEUROSCI.2159-07.2007 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 240VJ UT WOS:000251616000033 PM 18077701 ER PT J AU Sun, HY Nikolovska-Coleska, Z Lu, JF Meagher, JL Yang, CY Qiu, S Tomita, Y Ueda, Y Jiang, S Krajewski, K Roller, PP Stuckey, JA Wang, SM AF Sun, Haiying Nikolovska-Coleska, Zaneta Lu, Jianfeng Meagher, Jennifer L. Yang, Chao-Yie Qiu, Su Tomita, York Ueda, Yumi Jiang, Sheng Krajewski, Krzysztof Roller, Peter P. Stuckey, Jeanne A. Wang, Shaomeng TI Design, synthesis, and characterization of a potent, nonpeptide, cell-permeable, bivalent smac mimetic that concurrently targets both the BIR2 and BIR3 domains in XIAP SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID X-LINKED INHIBITOR; STRUCTURAL BASIS; CASPASE INHIBITION; IAP PROTEINS; APOPTOSIS; SMAC/DIABLO; BINDING; CANCER; ANTAGONISTS; ACTIVATION AB XIAP is a central apoptosis regulator that inhibits apoptosis by binding to and inhibiting the effectors caspase-3/-7 and an initiator caspase-9 through its BIR2 and BIR3 domains, respectively. Smac protein in its dimeric form effectively antagonizes XIAP by concurrently, targeting both its BIR2 and BIR3 domains. We report the design, synthesis, and characterization of a nonpeptide, cell-permeable, bivalent small-molecule (SM-164) which mimics Smac protein for targeting XIAP. Our study shows that SM-164 binds to XIAP containing both BIR domains with an IC50 value of 1.39 nM, being 300 and 7000 times more potent than its monovalent counterparts and the natural Smac AVPI peptide, respectively. SM-164 concurrently interacts with both BIR domains in XIAP and functions as an ultrapotent antagonist of XIAP in both cell-free functional and cell-based assays. SM-164 targets cellular XIAP and effectively induces apoptosis at concentrations as low as 1 nM in the HL-60 leukemia cell line. The potency of bivalent SM-164 in binding, functional, and cellular assays is 2-3 orders of magnitude higher than its corresponding monovalent Smac mimetics. C1 Univ Michigan, Ctr Comprehens Canc, Dept Internal Med, Inst Life Sci,Biophys Res Div, Ann Arbor, MI 48109 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. NIH, Natl Canc Inst, Lab Med Chem, Ft Detrick, MD 21702 USA. RP Wang, SM (reprint author), Univ Michigan, Ctr Comprehens Canc, Dept Internal Med, Inst Life Sci,Biophys Res Div, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM shaomeng@med.umich.edu RI Wang, Shaomeng/E-9686-2010 FU NCI NIH HHS [R01 CA109025, R01 CA109025-01, R01 CA109025-02, R01 CA109025-03, R01 CA109025-04, R01 CA127551, R01CA109025] NR 46 TC 113 Z9 120 U1 1 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 12 PY 2007 VL 129 IS 49 BP 15279 EP 15294 DI 10.1021/ja074725f PG 16 WC Chemistry, Multidisciplinary SC Chemistry GA 238VX UT WOS:000251477400041 PM 17999504 ER PT J AU Tao-Cheng, JH AF Tao-Cheng, J. -H. TI Ultrastructural localization of active zone and synaptic vesicle proteins in a preassembled multi-vesicle transport aggregate SO NEUROSCIENCE LA English DT Article DE bassoon; piccolo; VAMP; SV2; synaptotagmin; synapsin l ID CULTURED HIPPOCAMPAL-NEURONS; PRESYNAPTIC CYTOMATRIX; MEMBRANE-PROTEINS; AXONS; PICCOLO; BASSOON; ASSOCIATION; DYNAMICS; RELEASE; SNAP-25 AB Although it has been suggested that presynaptic active zone (AZ) may be preassembled, it is still unclear which entities carry the various proteins to the AZ during synaptogenesis. Here, I propose that aggregates of dense core vesicles (DCV) and small clear vesicles in the axons of young rat hippocampal cultures are carriers containing preformed AZ and synaptic vesicle (SV) components on their way to developing synapses. The aggregates were positively labeled with antibodies against Bassoon and Piccolo (two AZ cytomatrix proteins), VAMP, SV2, synaptotagmin (three SV membrane proteins), and synapsin I (a SV-associated protein). Bassoon and Piccolo labeling were localized at dense material both in the aggregates and at the AZ. In addition to the SV at the synapses, the SV membrane proteins labeled the clear vesicles in the aggregate as well as many other SV-Iike and pleiomorphic vesicular structures in the axons, and synapsin I labeling was associated with the vesicles in the aggregates. In single sections, these axonal vesicle aggregates were similar to 0.22 by 0.13 mu m in average dimensions and contain one to two DCV and five to six small clear vesicles. Serial sections confirmed that the aggregates were not synaptic junctions sectioned en face. Labeling intensities of Bassoon and Piccolo measured from serially sectioned transport aggregates and AZ were within range of each other, suggesting that one or a few aggregates, but not individual DCV, can carry sufficient Bassoon and Piccolo to form an AZ. The present findings provide the first ultrastructural evidence localizing various AZ and SV proteins in a preassembled multi-vesicle transport aggregate that has the potential to quickly form a functional active zone. Published by Elsevier Ltd on behalf of IBRO. C1 [Tao-Cheng, J. -H.] NIH, NINDS, EM Facil, Bethesda, MD 20892 USA. RP Tao-Cheng, JH (reprint author), NIH, NINDS, EM Facil, Bldg 49, Rm 3A50, Bethesda, MD 20892 USA. EM chengs@ninds.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 24 TC 44 Z9 44 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC 12 PY 2007 VL 150 IS 3 BP 575 EP 584 DI 10.1016/j.neuroscience.2007.09.031 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 244JU UT WOS:000251863000007 PM 17977664 ER PT J AU Finkelman, BS Viboud, C Koelle, K Ferrari, MJ Bharti, N Grenfell, BT AF Finkelman, Brian S. Viboud, Cecile Koelle, Katia Ferrari, Matthew J. Bharti, Nita Grenfell, Bryan T. TI Global Patterns in Seasonal Activity of Influenza A/H3N2, A/H1N1, and B from 1997 to 2005: Viral Coexistence and Latitudinal Gradients SO PLOS ONE LA English DT Article AB Despite a mass of research on the epidemiology of seasonal influenza, overall patterns of infection have not been fully described on broad geographic scales and for specific types and subtypes of the influenza virus. Here we provide a descriptive analysis of laboratory-confirmed influenza surveillance data by type and subtype (A/H3N2, A/H1N1, and B) for 19 temperate countries in the Northern and Southern hemispheres from 1997 to 2005, compiled from a public database maintained by WHO (FluNet). Key findings include patterns of large scale co-occurrence of influenza type A and B, interhemispheric synchrony for subtype A/H3N2, and latitudinal gradients in epidemic timing for type A. These findings highlight the need for more countries to conduct year-round viral surveillance and report reliable incidence data at the type and subtype level, especially in the Tropics. C1 [Finkelman, Brian S.; Ferrari, Matthew J.; Bharti, Nita; Grenfell, Bryan T.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Eberly Coll Sci, University Pk, PA 16802 USA. [Viboud, Cecile; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Koelle, Katia] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. RP Finkelman, BS (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Eberly Coll Sci, University Pk, PA 16802 USA. EM bsf143@psu.edu OI Finkelman, Brian/0000-0002-4348-8208 FU Schreyer Honors College Summer 2007 Research Scholarship FX Funding for this work was provided by the Schreyer Honors College Summer 2007 Research Scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 105 Z9 106 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 12 PY 2007 VL 2 IS 12 AR e1296 DI 10.1371/journal.pone.0001296 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JE UT WOS:000207459500015 PM 18074020 ER PT J AU Sharma, S Brosh, RM AF Sharma, Sudha Brosh, Robert M., Jr. TI Human RECQ1 Is a DNA Damage Responsive Protein Required for Genotoxic Stress Resistance and Suppression of Sister Chromatid Exchanges SO PLOS ONE LA English DT Article AB Background. DNA helicases are ubiquitous enzymes that unwind DNA in an ATP-dependent and directionally specific manner. Unwinding of double-stranded DNA is essential for the processes of DNA repair, recombination, transcription, and DNA replication. Five human DNA helicases sharing sequence similarity with the E. coli RecQ helicase have been identified. Three of the human RecQ helicases are implicated in hereditary diseases (Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome) which display clinical symptoms of premature aging and cancer. RECQ1 helicase is the most highly expressed of the human RecQ helicases; however, a genetic disease has yet not been linked to mutations in the RECQ1 gene, and the biological functions of human RECQ1 in cellular DNA metabolism are not known. Methodology/Principal Findings. In this study, we report that RECQ1 becomes phosphorylated upon DNA damage and forms irradiation-induced nuclear foci that associate with chromatin in human cells. Depletion of RECQ1 renders human cells sensitive to DNA damage induced by ionizing radiation or the topoisomerase inhibitor camptothecin, and results in spontaneous gamma-H2AX foci and elevated sister chromatid exchanges, indicating aberrant repair of DNA breaks. Consistent with a role in homologous recombinational repair, endogenous RECQ1 is associated with the strand exchange protein Rad51 and the two proteins directly interact with high affinity. Conclusion/Significance. Collectively, these results provide the first evidence for a role of human RECQ1 in the response to DNA damage and chromosomal stability maintenance and point to the vital importance of RECQ1 in genome homeostasis. C1 [Sharma, Sudha; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA. EM BroshR@grc.nia.nih.gov OI Sharma, Sudha/0000-0003-2765-2482 FU Intramural Research Program of the NIH-NIA FX This research was supported by the Intramural Research Program of the NIH-NIA. NR 62 TC 52 Z9 53 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 12 PY 2007 VL 2 IS 12 AR e1297 DI 10.1371/journal.pone.0001297 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JE UT WOS:000207459500016 PM 18074021 ER PT J AU Yates, A Graw, F Barber, DL Ahmed, R Regoes, RR Antia, R AF Yates, Andrew Graw, Frederik Barber, Daniel L. Ahmed, Rafi Regoes, Roland R. Antia, Rustom TI Revisiting Estimates of CTL Killing Rates In Vivo SO PLOS ONE LA English DT Article AB Recent experimental advances have allowed the estimation of the in vivo rates of killing of infected target cells by cytotoxic T lymphocytes (CTL). We present several refinements to a method applied previously to quantify killing of targets in the spleen using a dynamical model. We reanalyse data previously used to estimate killing rates of CTL specific for two epitopes of lymphocytic choriomeningitis virus (LCMV) in mice and show that, contrary to previous estimates the "killing rate'' of effector CTL is approximately twice that of memory CTL. Further, our method allows the fits to be visualized, and reveals one potentially interesting discrepancy between fits and data. We discuss extensions to the basic CTL killing model to explain this discrepancy and propose experimental tests to distinguish between them. C1 [Yates, Andrew; Antia, Rustom] Emory Univ, Dept Biol, Atlanta, GA 30322 USA. [Graw, Frederik; Regoes, Roland R.] ETH, Inst Integrat Biol, Zurich, Switzerland. [Barber, Daniel L.] NIAID, Bethesda, MD 20892 USA. [Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA USA. RP Yates, A (reprint author), Emory Univ, Dept Biol, Atlanta, GA 30322 USA. EM ayates2@emory.edu RI Regoes, Roland/A-6538-2008 FU Swiss National Science Foundation; NIH [RO1 AI 49334] FX RRR and FG gratefully acknowledge the financial support of the Swiss National Science Foundation. AY and Rustom Antia were supported by NIH grant RO1 AI 49334 to Rustom Antia. The funders played no other role in the study. NR 25 TC 28 Z9 28 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 12 PY 2007 VL 2 IS 12 AR e1301 DI 10.1371/journal.pone.0001301 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JE UT WOS:000207459500020 PM 18074025 ER PT J AU Frey, SE Newman, FK Kennedy, JS Sobek, V Ennis, FA Hill, H Yan, LK Chaplin, P Vollmar, J Chaitman, BR Belshe, RB AF Frey, Sharon E. Newman, Frances K. Kennedy, Jeffrey S. Sobek, Vera Ennis, Francis A. Hill, Heather Yan, Lihan K. Chaplin, Paul Vollmar, Jens Chaitman, Bernard R. Belshe, Robert B. TI Clinical and immunologic responses to multiple doses of IMVAMUNE (R) (Modified Vaccinia Ankara) followed by Dryvax (R) challenge SO VACCINE LA English DT Article DE IMVAMUNE (R); MVA; Dryvax (R) ID SMALLPOX VACCINE; MONKEYPOX VIRUS; STRAIN MVA; IMMUNOGENICITY; INDIVIDUALS; VARIOLA; SAFETY AB Smallpox vaccination with replication deficient vaccinia strains such as Modified Vaccinia Ankara (MVA) may induce protective immunity with improved safety and tolerability profiles compared with currently available smallpox vaccines. Ninety subjects were randomized equally to six groups in a partially blinded, randomized, controlled clinical trial. lMVAMUNE (R) (MVA-BN (R), Bavarian Nordic A/S, Kvistgard, Denmark) vaccine or placebo was administered at Study Days 0 and 28 by subcutaneous or intramuscular injection and five groups were challenged with Dryvax (R) at study Day 112. Vaccination with two doses of IMVAMUNE (R) was safe and well tolerated compared to Dryvax (R). INIVAMUNE (R) produced comparable cellular and Immoral immune responses to one dose of Dryvax (R) and the immunity induced appears robust 90 days post-vaccination by evidence of attenuated primary cutaneous reaction responses following Dryvax (R). IMVAMUNE (R) vaccination prior to Dryvax (R) reduced virus replication at the Dryvax (R) site, decreased the size of the primary cutaneous lesion, and decreased the time to healing but did not completely ameliorate the immune response. (c) 2007 Elsevier Ltd. All fights reserved. C1 [Frey, Sharon E.; Newman, Frances K.; Belshe, Robert B.] St Louis Univ, Sch Med, Dept Med, St Louis, MO 63104 USA. [Frey, Sharon E.; Newman, Frances K.; Belshe, Robert B.] NIAID, Vaccine Treatment & Evaluat Unit, St Louis, MO 63104 USA. [Kennedy, Jeffrey S.; Ennis, Francis A.] Univ Massachusetts, Med Ctr, Ctr Infect Dis & Vaccine Res, Worcester, MA 01655 USA. [Hill, Heather; Yan, Lihan K.] EMMES Corp, Rockville, MD 20850 USA. [Sobek, Vera; Chaplin, Paul; Vollmar, Jens] Bavarian Nord AS, DK-3490 Kvistgard, Denmark. [Chaitman, Bernard R.] St Louis Univ, Sch Med, Div Cardiol, Dept Med, St Louis, MO 63103 USA. RP Frey, SE (reprint author), St Louis Univ, Sch Med, Dept Med, 1100 S Grand Blvd DRC-8, St Louis, MO 63104 USA. EM freyse@slu.edu FU NIAID NIH HHS [N01-AI-25464, N01 AI025464, N01AI25464, U10-AI-05719] NR 19 TC 54 Z9 54 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 12 PY 2007 VL 25 IS 51 BP 8562 EP 8573 DI 10.1016/j.vaccine.2007.10.017 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 250EY UT WOS:000252284000010 PM 18036708 ER PT J AU McFeeters, RL Altieri, AS Cherry, S Tropea, JE Waugh, DS Byrd, RA AF McFeeters, Robert L. Altieri, Amanda S. Cherry, Scott Tropea, Joseph E. Waugh, David S. Byrd, R. Andrew TI The high-precision solution structure of Yersinia modulating protein YmoA provides insight into interaction with H-NS SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; HHA PROTEIN; OLIGOMERIZATION DOMAIN; CHEMICAL-SHIFT; CURVED DNA; EXPRESSION; NMR; ENTEROCOLITICA; GENE; BINDING AB The high-resolution solution structure of Yersinia modulating protein YmoA is presented. The protein is all helical with the first three of four helices forming the central core. Structures calculated with only NOE and dihedral restraints exhibit a backbone root-mean-square deviation (rmsd) of 0.77 angstrom. Upon refinement against H-alpha-C-alpha, H-N-N, and C-alpha-C' J-modulated residual dipolar couplings, the backbone rmsd improves to 0.22 angstrom. YmoA has a high amino acid sequence identity to and a similar overall fold to Escherichia coli hemolysin expression modulating protein Hha; however, structural differences do occur. YmoA is also found to be structurally similar to the histone-like nucleoid structuring protein H-NS, indicating that YmoA may intercalate into higher-order H-NS suprastructuting by substituting for an H-NS dimer. C1 NCI, Ctr Canc Res, Struc Biophys Lab & Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Byrd, RA (reprint author), NCI, Ctr Canc Res, Struc Biophys Lab & Macromol Crystallog Lab, Frederick, MD 21702 USA. EM rabyrd@ncifcrf.gov RI Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 FU Intramural NIH HHS; NCI NIH HHS [NC01-CO-12400] NR 46 TC 15 Z9 16 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 11 PY 2007 VL 46 IS 49 BP 13975 EP 13982 DI 10.1021/bi701210j PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238BI UT WOS:000251421900004 PM 18001134 ER PT J AU Taylor, RA Lord, CI Riesselman, MH Gripentrog, JM Leto, TL McPhail, LC Berdichevsky, Y Pick, E Jesaitis, AJ AF Taylor, Ross A. Lord, Connie I. Riesselman, Marcia H. Gripentrog, Jeannie M. Leto, Thomas L. McPhail, Linda C. Berdichevsky, Yevgeny Pick, Edgar Jesaitis, Algirdas J. TI Characterization of surface structure and p47(phox) SH3 domain-mediated conformational changes for human neutrophil flavocytochrome b SO BIOCHEMISTRY LA English DT Article ID PHAGOCYTE NADPH OXIDASE; CHRONIC GRANULOMATOUS-DISEASE; RESONANCE ENERGY-TRANSFER; RESPIRATORY BURST OXIDASE; PHAGE-DISPLAY LIBRARIES; SRC HOMOLOGY-3 DOMAINS; CELL-FREE SYSTEM; CYTOCHROME B(558); PHOSPHATIDIC-ACID; P22(PHOX) SUBUNIT AB The heterodimeric, integral membrane protein flavocytochrome b (Cyt b) is the catalytic core of the phagocyte NADPH oxidase and generates superoxide which plays a critical role in host defense. To better define the activation of superoxide production by this multisubunit enzyme complex, Cyt b-specific monoclonal antibodies (mAbs) and the p47(phox) SH3 domains (p47SH3(AB)) were used in the present study as probes to map surface structure and conformational dynamics in human neutrophil Cyt b. In pull-down and co-immunoprecipitation studies with detergent-solubilized Cyt b, the oxidase-inhibitory mAb CS9 was shown to share an overlapping binding site with p47SH3(AB) on the C-terminal region of the p22(phox) subunit. Similar studies demonstrated a surprising lack of overlap between the mAb 44.1 and CS9/p47SH3(AB) binding sites, and they indicated that the oxidase-inhibitory mAb NL7 binds a region physically separated from the p22phox C-terminal domain. Resonance energy transfer and size exclusion chromatography confirmed the above results for functionally reconstituted Cyt b and provided evidence that binding of both mAb CS9 and p47SH3(AB) altered the conformation of Cyt b. Further support that binding of the p47(phox) SH3 domains modulates the structure of Cyt b was obtained using a cell-free assay system where p47SH3(AB) enhanced superoxide production in the presence of a p67(phoz) (1-212)-Rac1(Q61L) fusion protein. Taken together, this study further characterizes the structure of human neutrophil Cyt b in both detergent micelles and reconstituted membrane bilayers, and it provides evidence that the cytosolic regulatory subunit P47(phox) modulates the conformation of Cyt b (in addition to serving as an adapter protein) during oxidase activation. C1 Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. NIAID, Mol Def Sect, Host Def Lab, NIH, Rockville, MD 20852 USA. Wake Forest Univ, Dept Biochem, Winston Salem, NC 27157 USA. Tel Aviv Univ, Sackler Fac Med, Julius Friedrich Cohnheim Minerva Ctr Phagocyte R, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, Ela Kodesz Inst Host Def Infect Dis, IL-69978 Tel Aviv, Israel. RP Taylor, RA (reprint author), Montana State Univ, Dept Microbiol, 109 Lewis Hall, Bozeman, MT 59717 USA. EM rosst@montana.edu RI McPhail, Linda/D-9505-2013; Pick, Edgar/B-1795-2008 OI McPhail, Linda/0000-0002-8670-306X; Pick, Edgar/0000-0003-4625-3233 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI 26711, R01 AI 22564, R01 AI022564] NR 72 TC 10 Z9 10 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 11 PY 2007 VL 46 IS 49 BP 14291 EP 14304 DI 10.1021/bi701626p PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238BI UT WOS:000251421900035 PM 18004884 ER PT J AU Singh, S Plassmeyer, M Gaur, D Miller, LH AF Singh, Subhash Plassmeyer, Matthew Gaur, Deepak Miller, Louis H. TI Mononeme: A new secretory organelle in Plasmodium falciparum merozoites identified by localization of rhomboid-1 protease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE malaria ID APICAL MEMBRANE ANTIGEN-1; MALARIA PARASITE; INVASION; MICROTUBULES; ERYTHROCYTES; ORGANIZATION; MICRONEMES; PROTEINS; FAMILY; SPECIFICITY AB Compartmentalization of proteins into subcellular organelles in eukaryotic cells is a fundamental mechanism of regulating complex cellular functions. Many proteins of Plasmodium, falciparum merozoites involved in invasion are compartmentalized into apical organelles. We have identified a new merozoite organelle that contains P. falciparum rhomboid-1 (PfROM1), a protease that cleaves the transmembrane regions of proteins involved in invasion. By immunoconfocal microscopy, PfROM1 was localized to a single, thread-like structure on one side of the merozoites that appears to be in close proximity to the subpellicular microtubules. PfROM1 was not found associated with micronemes, rhoptries, or dense granules, the three identified secretory organelles of invasion. Release of merozoites from schizonts resulted in the movement of PfROM1 from the lateral asymmetric localization to the merozoite apical pole and the posterior pole. We have named this single thread-like organelle in merozoites, the mononeme. C1 [Singh, Subhash; Plassmeyer, Matthew; Gaur, Deepak; Miller, Louis H.] NIAID, Malaria Cell Biol Sect, Lab Malaria & Vector Res, Natl Inst Hlth, Rockville, MD 20852 USA. RP Singh, S (reprint author), NIAID, Malaria Cell Biol Sect, Lab Malaria & Vector Res, Natl Inst Hlth, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM susingh@mail.nih.gov; lomiller@mail.nih.gov FU Intramural NIH HHS NR 33 TC 37 Z9 37 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 11 PY 2007 VL 104 IS 50 BP 20043 EP 20048 DI 10.1073/pnas.0709999104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 242UR UT WOS:000251752200071 PM 18048320 ER PT J AU Krueger, F McCabe, K Moll, J Kriegeskorte, N Zahn, R Strenziok, M Heinecke, A Grafman, J AF Krueger, Frank McCabe, Kevin Moll, Jorge Kriegeskorte, Nikolaus Zahn, Roland Strenziok, Maren Heinecke, Armin Grafman, Jordan TI Neural correlates of trust SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE attachment; neuroeconomics; reward; social; functional MRI ID ROMANTIC LOVE; COOPERATION; OXYTOCIN; GAME; RESPONSES; CORTEX; REWARD; EXCHANGE; SYSTEMS; BRAIN AB Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became idirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species. C1 [Krueger, Frank; Strenziok, Maren; Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [McCabe, Kevin] George Mason Univ, Ctr Study Neuroecon, Fairfax, VA 22030 USA. [Moll, Jorge] LABS D Or Hosp Network, Cognit & Behav Neurosci Unit, BR-2228080 Rio De Janeiro, Brazil. [Kriegeskorte, Nikolaus] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Zahn, Roland] Univ Manchester, Neurosci & Aphasia Res Unit, Sch Psychol Sci, Manchester M13 9PL, Lancs, England. [Heinecke, Armin] Brain Innovat BV, NL-6201 BC Maastricht, Netherlands. RP Grafman, J (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA. EM GrafmanJ@ninds.nih.gov RI Zahn, Roland/C-4665-2008; Moll, Jorge/B-2654-2013; OI Zahn, Roland/0000-0002-8447-1453; Kriegeskorte, Nikolaus/0000-0001-7433-9005; Grafman, Jordan H./0000-0001-8645-4457; McCabe, Kevin/0000-0003-0544-157X FU Intramural NIH HHS NR 44 TC 130 Z9 134 U1 3 U2 30 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 11 PY 2007 VL 104 IS 50 BP 20084 EP 20089 DI 10.1073/pnas.0710103104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 242UR UT WOS:000251752200078 PM 18056800 ER PT J AU Canto, JG Goldberg, RJ Hand, MM Bonow, RO Sopko, G Pepine, CJ Long, T AF Canto, John G. Goldberg, Robert J. Hand, Mary M. Bonow, Robert O. Sopko, George Pepine, Carl J. Long, Terry TI Symptom presentation of women with acute coronary syndromes - Myth vs reality SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; MULTICENTER CHEST PAIN; ACUTE CARDIAC ISCHEMIA; GENDER-DIFFERENCES; SEX-DIFFERENCES; HEART-DISEASE; CLINICAL CHARACTERISTICS; ANGINA-PECTORIS; UNSTABLE ANGINA; RISK-FACTORS AB Background: Optimal diagnosis and timely treatment of patients with an acute coronary syndrome (ACS) depends on distinguishing differences between popular "myths" about ischemic symptoms in women and men. Chest pain or discomfort is regarded as the hallmark symptom of ACS, and its absence is regarded as "atypical" presentation. This review describes the presenting symptoms of ACS in women compared with men and ascertains whether women should have a symptom message that is separate or different from that for men. Methods: MEDLINE (1970-2005), bibliographies of articles, and pertinent abstracts were reviewed, focusing on studies of ACS presentation, especially those reporting differences in symptoms by sex. This analysis included 69 of 361 possible studies. Data regarding symptom presentation were recorded. Results: The published literature lacks standardization in characterizing ACS presentation, data collection, and reporting of symptoms. Approximately one-third of patients in the large cohort studies and one-quarter of patients in the smaller reports and direct patient interviews presented without chest pain or discomfort. The absence of chest pain or discomfort with ACS was noted more commonly in women than in men in both the cumulative summary from large cohort studies (37% vs 27%) and the single-center and small reports or interviews (30% vs 17%). Conclusions: Women are significantly less likely to report chest pain or discomfort compared with men. These differences, however, are not likely large enough to warrant sex-specific public health messages regarding the symptoms of ACS at the present time. Further research must systematically investigate sex differences in the clinical presentation of ACS symptoms and must include standardized data collection efforts. C1 Watson Clin, Lakeland, FL 33805 USA. Univ Alabama, Birmingham, AL USA. Univ Massachusetts, Sch Med, Worcester, MA USA. NHLBI, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Florida, Coll Med, Gainesville, FL USA. RP Canto, JG (reprint author), Watson Clin, 1600 Lakeland Hill Blvd, Lakeland, FL 33805 USA. EM jcanto@watsonclinic.com NR 86 TC 144 Z9 145 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 10 PY 2007 VL 167 IS 22 BP 2405 EP 2413 DI 10.1001/archinte.167.22.2405 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 239SI UT WOS:000251537600004 PM 18071161 ER PT J AU Leitzmann, MF Park, Y Blair, A Ballard-Barbash, R Mouw, T Hollenbeck, AR Schatzkin, A AF Leitzmann, Michael F. Park, Yikyung Blair, Aaron Ballard-Barbash, Rachel Mouw, Traci Hollenbeck, Albert R. Schatzkin, Arthur TI Physical activity recommendations and decreased risk of mortality SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ALL-CAUSE MORTALITY; CORONARY-HEART-DISEASE; HARVARD ALUMNI HEALTH; LEISURE-TIME; CANCER PREVENTION; ACTIVITY SCALE; ELDERLY PASE; OLDER-ADULTS; MEN; FITNESS AB Background: Whether national physical activity recommendations are related to mortality benefit is incompletely understood. Methods: We prospectively examined physical activity guidelines in relation to mortality among 252 925 women and men aged 50 to 71 years in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Physical activity was assessed using 2 self-administered baseline questionnaires. Results: During 1 265 347 person-years of follow-up, 7900 participants died. Compared with being inactive, achievement of activity levels that approximate the recommendations for moderate activity ( at least 30 minutes on most days of the week) or vigorous exercise ( at least 20 minutes 3 times per week) was associated with a 27% ( relative risk [RR], 0.73; 95% confidence interval [ CI], 0.68-0.78) and 32% ( RR, 0.68; 95% CI, 0.64-0.73) decreased mortality risk, respectively. Physical activity reflective of meeting both recommendations was related to substantially decreased mortality risk overall ( RR, 0.50; 95% CI, 0.46-0.54) and in subgroups, including smokers ( RR, 0.48; 95% CI, 0.44-0.53) and nonsmokers ( RR, 0.54; 95% CI, 0.45-0.64), normal weight ( RR, 0.45; 95% CI, 0.39-0.52) and overweight or obese individuals ( RR, 0.48; 95% CI, 0.44-0.54), and those with 2 h/d ( RR, 0.53; 95% CI, 0.44-0.63) and more than 2 h/d of television or video watching ( RR, 0.50; 95% CI, 0.45-0.55). Engaging in physical activity at less than recommended levels was also related to reduced mortality risk ( RR, 0.81; 95% CI, 0.76-0.86). Conclusions: Following physical activity guidelines is associated with lower risk of death. Mortality benefit may also be achieved by engaging in less than recommended activity levels. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. AARP, Knowledge Management, Washington, DC USA. RP Leitzmann, MF (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM leitzmann@mailnih.gov OI Park, Yikyung/0000-0002-6281-489X FU Intramural NIH HHS NR 54 TC 184 Z9 186 U1 3 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 10 PY 2007 VL 167 IS 22 BP 2453 EP 2460 DI 10.1001/archinte.167.22.2453 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 239SI UT WOS:000251537600011 PM 18071167 ER PT J AU Mitrou, PN Kipnis, V Thiebaut, ACM Reedy, J Subar, AF Wirfalt, E Flood, A Mouw, T Hollenbeck, AR Leitzmann, MF Schatzkin, A AF Mitrou, Panagiota N. Kipnis, Victor Thiebaut, Anne C. M. Reedy, Jill Subar, Amy F. Wirfalt, Elisabet Flood, Andrew Mouw, Traci Hollenbeck, Albert R. Leitzmann, Michael F. Schatzkin, Arthur TI Mediterranean dietary pattern and prediction of all-cause mortality in a US population - Results from the NIH-AARP diet and health study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ELDERLY-PEOPLE; COHORT; SURVIVAL; INFLAMMATION; CANCER; LIFE; QUESTIONNAIRE; ASSOCIATION; ADHERENCE; LONGEVITY AB Background: The Mediterranean diet has been suggested to play a beneficial role for health and longevity. However, to our knowledge, no prospective US study has investigated the Mediterranean dietary pattern in relation to mortality. Methods: Study participants included 214 284 men and 166 012 women in the National Institutes of Health (NIH)-AARP ( formerly known as the American Association of Retired Persons) Diet and Health Study. During follow-up for all-cause mortality (1995-2005), 27 799 deaths were documented. In the first 5 years of follow-up, 5985 cancer deaths and 3451 cardiovascular disease (CVD) deaths were reported. We used a 9-point score to assess conformity with the Mediterranean dietary pattern ( components included vegetables, legumes, fruits, nuts, whole grains, fish, monounsaturated fat saturated fat ratio, alcohol, and meat). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using age- and multivariate-adjusted Cox models. Results: The Mediterranean diet was associated with reduced all-cause and cause-specific mortality. In men, the multivariate HRs comparing high to low conformity for all-cause, CVD, and cancer mortality were 0.79 ( 95% CI, 0.76-0.83), 0.78 ( 95% CI, 0.69-0.87), and 0.83 ( 95% CI, 0.76-0.91), respectively. In women, an inverse association was seen with high conformity with this pattern: decreased risks that ranged from 12% for cancer mortality to 20% for all-cause mortality (P=.04 and P <.001, respectively, for the trend). When we restricted our analyses to never smokers, associations were virtually unchanged. Conclusion: These results provide strong evidence for a beneficial effect of higher conformity with the Mediterranean dietary pattern on risk of death from all causes, including deaths due to CVD and cancer, in a US population. C1 Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Appl Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Lund Univ, Dept Clin Sci, Malmo, Sweden. Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. AARP, Washington, DC USA. RP Mitrou, PN (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. EM pm277@medschl.cam.ac.uk FU Intramural NIH HHS NR 35 TC 237 Z9 242 U1 5 U2 29 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 10 PY 2007 VL 167 IS 22 BP 2461 EP 2468 DI 10.1001/archinte.167.22.2461 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 239SI UT WOS:000251537600012 PM 18071168 ER PT J AU Bacchetti, P Tien, PC Seaberg, EC O'Brien, TR Augenbraun, MH Kral, AH Busch, MP Edlin, BR AF Bacchetti, Peter Tien, Phyllis C. Seaberg, Eric C. O'Brien, Thomas R. Augenbraun, Michael H. Kral, Alex H. Busch, Michael P. Edlin, Brian R. TI Estimating past hepatitis C infection risk from reported risk factor histories: implications for imputing age of infection and modeling fibrosis progression SO BMC INFECTIOUS DISEASES LA English DT Article ID INJECTION-DRUG USERS; NEW-YORK-CITY; IMMUNODEFICIENCY-VIRUS-INFECTION; WOMENS INTERAGENCY HIV; SAN-FRANCISCO; NATURAL-HISTORY; LIVER FIBROSIS; REGRESSION-ANALYSIS; VIRAL-INFECTIONS; HCV INFECTION AB Background: Chronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure. Study of fibrosis progression often relies on imputing the time of infection, often as the reported age of first injection drug use. We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates. Methods: We analyzed cross-sectional data on hepatitis C antibody status and reported risk factor histories from two large studies, the Women's Interagency HIV Study and the Urban Health Study, using modern survival analysis methods for current status data to model past infection risk year by year. We compared fitted distributions of past infection risk to reported age of first injection drug use. Results: Although injection drug use appeared to be a very strong risk factor, models for both studies showed that many subjects had considerable probability of having been infected substantially before or after their reported age of first injection drug use. Persons reporting younger age of first injection drug use were more likely to have been infected after, and persons reporting older age of first injection drug use were more likely to have been infected before. Conclusion: In cross-sectional studies of fibrosis progression where date of HCV infection is estimated from risk factor histories, modern methods such as multiple imputation should be used to account for the substantial uncertainty about when infection occurred. The models presented here can provide the inputs needed by such methods. Using reported age of first injection drug use as the time of infection in studies of fibrosis progression is likely to produce a spuriously strong association of younger age of infection with slower rate of progression. C1 [Bacchetti, Peter] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Tien, Phyllis C.] Univ Calif San Francisco, Vet Affairs Med Ctr, Dept Med, Infect Dis Sect, San Francisco, CA 94121 USA. [Seaberg, Eric C.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [O'Brien, Thomas R.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Augenbraun, Michael H.] Suny Downstate Med Ctr, Div Infect Dis, Brooklyn, NY 11203 USA. [Kral, Alex H.] Univ Calif San Francisco, Dept Family & Community Med, RTI Int, San Francisco, CA 94143 USA. [Busch, Michael P.] Univ Calif San Francisco, Blood Syst Res Inst, Dept Lab Med, San Francisco, CA 94143 USA. [Edlin, Brian R.] Cornell Univ, Weill Med Coll, Ctr Study Hepatitis C, New York, NY 10021 USA. [Edlin, Brian R.] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. RP Bacchetti, P (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. EM peter@biostat.ucsf.edu; ptien@ucsf.edu; eseaberg@jhsph.edu; obrient@exchange.nih.gov; Michael.Augenbraun@downstate.edu; akral@rti.org; mbusch@bloodsystems.org; bre2002@med.cornell.edu OI Edlin, Brian/0000-0001-8172-8797 FU CSAT SAMHSA HHS [H79-TI12103]; Intramural NIH HHS; NCI NIH HHS [N02-CP-91027]; NCRR NIH HHS [M01 RR000071, M01 RR000079, M01-RR-00071, M01 RR000083, M01-RR-00083, M01-RR-00079]; NIAID NIH HHS [U01 AI034989, U01 AI031834, U01 AI034994, UO1-AI-34993, UO1-AI-42590, K23 AI066943, K23 AI066943-05, R01 AI055085, R01 AI069952, R01 AI069952-01, R01 AI55085, U01 AI034993, U01 AI035004, U01 AI042590, U01-AI-35004, UO1-AI-31834, UO1-AI-34989, UO1-AI-34994]; NICHD NIH HHS [U01 HD032632, UO1-HD-32632]; NIDA NIH HHS [R01 DA016159, R01-DA13245, R01 DA012109, R01 DA013245, R01-DA16159] NR 47 TC 17 Z9 17 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD DEC 10 PY 2007 VL 7 AR 145 DI 10.1186/1471-2334-7-145 PG 11 WC Infectious Diseases SC Infectious Diseases GA 262IK UT WOS:000253142000002 PM 18070362 ER PT J AU Callen, E Nussenzweig, MC Nussenzweig, A AF Callen, E. Nussenzweig, M. C. Nussenzweig, A. TI Breaking down cell cycle checkpoints and DNA repair during antigen receptor gene assembly SO ONCOGENE LA English DT Review DE DNA repair; cell cycle checkpoints; class-switching; V(D)J recombination; ATM; lymphoma ID CLASS-SWITCH RECOMBINATION; ATM-DEFICIENT MICE; DOUBLE-STRAND BREAKS; GENOMIC INSTABILITY; V(D)J RECOMBINATION; HISTONE H2AX; CHROMOSOME ABERRATIONS; REGION RECOMBINATION; DAMAGE CHECKPOINT; HUMAN LYMPHOCYTES AB Double-strand breaks (DSBs) are intermediates in several physiological processes including V(D)J and class switch recombination. They are also potent substrates for chromosomal translocations that arise as by-products of antigen receptor gene assembly in lymphocytes. ATM is one among several key proteins involved in the detection, signaling and repair of DNA breaks. Despite redundancies in DSB signaling pathways, it has recently been demonstrated that ATM deficient lymphocytes can survive and proliferate several generations in vitro and in vivo despite harboring terminally deleted chromosomes produced by V(D)J recombination. In this review, we discuss how two complementary genome maintenance functions mediated by ATM prevent lymphocytes from adapting to persistent DNA damage. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Howard Hughes Med Inst, New York, NY USA. RP Callen, E (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM callene@mail.nih.gov NR 57 TC 19 Z9 19 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 10 PY 2007 VL 26 IS 56 BP 7759 EP 7764 DI 10.1038/sj.onc.1210873 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 239SL UT WOS:000251537900006 PM 18066088 ER PT J AU Lin, B Chernomordik, V Gandjbakhche, A Matthews, D Demos, S AF Lin, Bevin Chernomordik, Victor Gandjbakhche, Amir Matthews, Dennis Demos, Stavros TI Investigation of signal dependence on tissue thickness in near infrared spectral imaging SO OPTICS EXPRESS LA English DT Article ID LIGHT-SCATTERING; IN-VIVO; FLUORESCENCE SPECTROSCOPY; OPTICAL SPECTROSCOPY; POLARIZATION; REFLECTANCE; DIAGNOSIS; CANCER; MODELS; CELLS AB The signal intensity in near infrared autofluorescence and polarization sensitive light scattering imaging is explored as a function of tissue thickness using homogeneous porcine cardiac tissue samples as a model system. Eight images are recorded from each tissue sample including two autofluorescence images obtained under 408 nm and 633 nm excitation and six light scattering images acquired with alternating linear polarization orientations (parallel or perpendicular) under 700 nm, 850 nm, and 1000 nm linearly polarized illumination. The mean image intensity of each sample for each imaging method is plotted as a function of tissue thickness. The experimental results indicate a strong dependence of the detected signal on tissue thickness up to approximately 2 mm. Furthermore, the intensity of the spectral ratio images also exhibit thickness-dependent changes up to about 3 mm. The behavior of the light scattering experimental data was reproduced using a mathematical model based on a modified version of the random walk theory of photon migration. (C) 2007 Optical Society of America. C1 [Lin, Bevin; Matthews, Dennis; Demos, Stavros] Univ Calif Davis, Ctr Biophoton Sci & Technol, Sacramento, CA 95817 USA. [Matthews, Dennis; Demos, Stavros] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA. [Chernomordik, Victor; Gandjbakhche, Amir] NIH, Bethesda, MD 20892 USA. RP Lin, B (reprint author), Univ Calif Davis, Ctr Biophoton Sci & Technol, 2700 Stockton Blvd,Suite 1400, Sacramento, CA 95817 USA. EM belin@ucdavis.edu NR 23 TC 3 Z9 3 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 10 PY 2007 VL 15 IS 25 BP 16581 EP 16595 DI 10.1364/OE.15.016581 PG 15 WC Optics SC Optics GA 240YT UT WOS:000251624800030 PM 19550947 ER PT J AU Schindler, CW Graczyk, Z Gilman, JP Negus, SS Bergman, J Mello, NK Goldberg, SR AF Schindler, Charles W. Graczyk, Zofi Gilman, Joanne P. Negus, S. Stevens Bergman, Jack Mello, Nancy K. Goldberg, Steven R. TI Effects of kappa opioid agonists alone and in combination with cocaine on heart rate and blood pressure in conscious squirrel monkeys SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE kappa opioid; blood pressure; heart rate; cocaine; Squirrel monkey ID CARDIOVASCULAR-RESPONSES; ANESTHETIZED RAT; OPIATE AGONISTS; RECEPTOR; ETHYLKETOCYCLAZOCINE; ETHYLKETAZOCINE; DISCRIMINATION; MECHANISMS; DYNORPHIN AB As kappa agonists have been proposed as treatments for cocaine abuse, the cardiovascular effects of the kappa opioid receptor agonists ethylketocyclazocine (EKC) and enadoline were investigated in conscious squirrel monkeys. Both EKC and enadoline increased heart rate with little effect on blood pressure. This effect appeared to be specific for kappa receptors as the mu opioid agonist morphine did not mimic the effects of the kappa agonists. The opioid antagonist naltrexone, at a dose of 1.0 mg/kg, blocked the effect of EKC. An action at both central and peripheral receptors may be responsible for the heart rate increase following kappa agonist treatment. The ganglionic blocker chlorisondamine partially antagonized the effect of EKC on heart rate, suggesting central involvement, while the peripherally-acting agonist ICI 204,448 ((+/-)-1-[2,3- (Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) also increased heart rate, supporting a peripheral site of action. When given in combination with cocaine, EKC produced effects that were sub-additive, suggesting that the kappa agonists may be used safely as cocaine abuse treatments. (c) 2007 Elsevier B.V. All rights reserved. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, DHHS,NIH,Intramural Res Program, Baltimore, MD 21224 USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, DHHS,NIH,Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM cschindl@helix.nih.gov FU Intramural NIH HHS [Z01 DA000009-22]; NIDA NIH HHS [K05 DA000101, K05-DA00101, P01 DA014528, P01-DA14528, U19-DA11007] NR 39 TC 4 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD DEC 8 PY 2007 VL 576 IS 1-3 BP 107 EP 113 DI 10.1016/j.ejphar.2007.07.053 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 231JO UT WOS:000250943200013 PM 17707792 ER PT J AU Yoshioka, J Imahashi, K Gabel, SA Chutkow, WA Burds, AA Gannon, J Schulze, PC MacGillivray, C London, RE Murphy, E Lee, RT AF Yoshioka, Jun Imahashi, Kenichi Gabel, Scott A. Chutkow, William A. Burds, Aurora A. Gannon, Joseph Schulze, P. Christian MacGillivray, Catherine London, Robert E. Murphy, Elizabeth Lee, Richard T. TI Targeted deletion of Thioredoxin-Interacting Protein regulates cardiac dysfunction in response to pressure overload SO CIRCULATION RESEARCH LA English DT Article DE cardiac hypertrophy; reactive oxygen species; glucose ID OXIDATIVE STRESS; HYPERTROPHY; HEART; INHIBITION; CELLS; MICE AB Biomechanical overload induces cardiac hypertrophy and heart failure, and reactive oxygen species (ROS) play a role in both processes. Thioredoxin-Interacting Protein (Txnip) is encoded by a mechanically-regulated gene that controls cell growth and apoptosis in part through interaction with the endogenous dithiol antioxidant thioredoxin. Here we show that Txnip is a critical regulator of the cardiac response to pressure overload. We generated inducible cardiomyocyte-specific and systemic Txnip-null mice (Txnip-KO) using Flp/frt and Cre/loxP technologies. Compared with littermate controls, Txnip-KO hearts had attenuated cardiac hypertrophy and preserved left ventricular (LV) contractile reserve through 4 weeks of pressure overload; however, the beneficial effects were not sustained and Txnip deletion ultimately led to maladaptive LV remodeling at 8 weeks of pressure overload. Interestingly, these effects of Txnip deletion on cardiac performance were not accompanied by global changes in thioredoxin activity or ROS; instead, Txnip-KO hearts had a robust increase in myocardial glucose uptake. Thus, deletion of Txnip plays an unanticipated role in myocardial energy homeostasis rather than redox regulation. These results support the emerging concept that the function of Txnip is not as a simple thioredoxin inhibitor but as a metabolic control protein. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RP Lee, RT (reprint author), 65 Landsdowne St 279, Cambridge, MA 02139 USA. EM rlee@partners.org FU NHLBI NIH HHS [HL073809, HL048743]; NIGMS NIH HHS [U54 GM0646346] NR 19 TC 55 Z9 57 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC 7 PY 2007 VL 101 IS 12 BP 1328 EP 1338 DI 10.1161/CIRCRESAHA.106.160515 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 238KC UT WOS:000251445500016 PM 17916779 ER PT J AU Watanabe, K Hamada, S Bianco, C Mancino, M Nagaoka, T Gonzales, M Bailly, V Strizzi, L Salomon, DS AF Watanabe, Kazuhide Hamada, Shin Bianco, Caterina Mancino, Mario Nagaoka, Tadahiro Gonzales, Monica Bailly, Veronique Strizzi, Luigi Salomon, David S. TI Requirement of Glycosylphosphatidylinositol anchor of cripto-1 for trans activity as a nodal co-receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RIGHT ASYMMETRIC EXPRESSION; ONE-EYED-PINHEAD; EGF-CFC FAMILY; INTERCELLULAR TRANSFER; SIGNALING PATHWAY; PRION PROTEIN; MOUSE; CELLS; IDENTIFICATION; CANCER AB Cripto-1 (CR-1) has an indispensable role as a Nodal coreceptor for patterning of body axis in embryonic development. CR-1 is reported to have a paracrine activity as a Nodal co-receptor, although CR-1 is primarily produced as a glycosylphosphatidylinositol (GPI)-anchored membrane protein. Regulation of cis and trans function of CR-1 should be important to establish the precise body patterning. However, the mechanism by which GPI-anchored CR-1 can act in trans is not well known. Here we confirmed the paracrine activity of CR-1 by fluorescent cell-labeling and immunofluorescent staining. We generated COOH-terminal-truncated soluble forms of CR-1 based on the attachment site for the GPI moiety (omega-site), which we identified in the present study. GPI-anchored CR-1 has a significantly higher activity than COOH-terminal-truncated soluble forms to induce Nodal signal in trans as well as in cis. Moreover, transmembrane forms of CR-1 partially retained their ability to induce Nodal signaling only when type I receptor Activin-like kinase 4 was overexpressed. NTERA2/D1 cells, which express endogenous CR-1, lost the cell-surface expression of CR-1 after phosphatidylinositol-phospholipase C treatment and became refractory to stimulation of Nodal. These observations suggest that GPI attachment of CR-1 is required for the paracrine activity as a Nodal co-receptor. C1 NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Biogen Idec Inc, Cambridge, MA 02142 USA. RP Salomon, DS (reprint author), Bldg 37,Rm 1118B,37 Convent Dr, Bethesda, MD 20892 USA. EM salomond@mail.nih.gov OI Nagaoka, Tadahiro/0000-0002-9391-0243 FU Intramural NIH HHS NR 43 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 7 PY 2007 VL 282 IS 49 BP 35772 EP 35786 DI 10.1074/jbc.M707351200 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238OW UT WOS:000251458100039 PM 17925387 ER PT J AU Zapata, A Kivell, B Han, Y Javitch, JA Bolan, EA Kuraguntla, D Jaligam, V Oz, M Jayanthi, LD Samuvel, DJ Ramamoorthy, S Shippenberg, TS AF Zapata, Agustin Kivell, Bronwyn Han, Yang Javitch, Jonathan A. Bolan, Elizabeth A. Kuraguntla, David Jaligam, Vanaja Oz, Murat Jayanthi, Lankupalle D. Samuvel, Devadoss J. Ramamoorthy, Sammanda Shippenberg, Toni S. TI Regulation of dopamine transporter function and cell surface expression by D3 dopamine receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; ELEMENT-BINDING PROTEIN; WILD-TYPE MICE; D-3 RECEPTOR; IN-VIVO; PHOSPHATIDYLINOSITOL 3-KINASE; DEPENDENT MECHANISM; PHORBOL ESTERS; NEUROTRANSMITTER TRANSPORTERS; NOREPINEPHRINE TRANSPORTER AB D-3 dopamine receptors are expressed by dopamine neurons and are implicated in the modulation of presynaptic dopamine neurotransmission. The mechanisms underlying this modulation remain ill defined. The dopamine transporter, which terminates dopamine transmission via reuptake of released neurotransmitter, is regulated by receptor- and second messenger-linked signaling pathways. Whether D3 receptors regulate dopamine transporter function is unknown. We addressed this issue using a fluorescent imaging technique that permits real time quantification of dopamine transporter function in living single cells. Accumulation of the fluorescent dopamine transporter substrate trans-4-[4-(dimethylamino) styryl]-1-methylpyridinium (ASP(+)) in human embryonic kidney cells expressing human dopamine transporter was saturable and temperature-dependent. In cells co-expressing dopamine transporter and D3 receptors, the D2/D3 agonist quinpirole produced a rapid, concentration-dependent, and pertussis toxin-sensitive increase of ASP(+) uptake. Similar agonist effects were observed in Neuro2A cells and replicated in human embryonic kidney cells using a radioligand uptake assay in which binding to and activation of D3 receptors by [H-3] dopamine was prevented. D3 receptor stimulation activated phosphoinositide 3-kinase and MAPK. Inhibition of either kinase prevented the quinpirole-induced increase in uptake. D3 receptor activation differentially affected dopamine transporter function and subcellular distribution depending on the duration of agonist exposure. Biotinylation experiments revealed that the rapid increase of uptake was associated with increased cell surface and decreased intracellular expression and increased dopamine transporter exocytosis. In contrast, prolonged agonist exposure reduced uptake and transporter cell surface expression. These results demonstrate that D3 receptors regulate dopamine transporter function and identify a novel mechanism by which D3 receptors regulate extracellular dopamine concentrations. C1 NIDA, Integrat Neurosci Sect, NIH, Intramural Res Program,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Columbia Univ, Coll Phys & Surg, Ctr Mol Recognit, Dept Psychiat, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Ctr Mol Recognit, Dept Pharmacol, New York, NY 10032 USA. Med Univ S Carolina, Dept Neurosci, Div Neurosci Res, Charleston, SC 29425 USA. RP Shippenberg, TS (reprint author), NIDA, Integrat Neurosci Sect, NIH, Intramural Res Program,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM tshippen@intra.nida.nih.gov RI Oz, Murat/E-2148-2012; Kivell, Bronwyn/P-3140-2014 OI Kivell, Bronwyn/0000-0001-9699-553X FU Intramural NIH HHS; NIDA NIH HHS [K05 DA022413, DA11495, P50DA015369]; NIGMS NIH HHS [GM081054]; NIMH NIH HHS [MH062612, MH54137, MH57324] NR 71 TC 55 Z9 55 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 7 PY 2007 VL 282 IS 49 BP 35842 EP 35854 DI 10.1074/jbc.M611758200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238OW UT WOS:000251458100046 PM 17923483 ER PT J AU Liu, F Worthy, KM Bindu, LK Fisher, RJ Burke, TR AF Liu, Fa Worthy, Karen M. Bindu, Lakshman K. Fisher, Robert J. Burke, Terrence R., Jr. TI Structural examination of ring-closing metathesis-derived 15-member macrocycles as Grb2 SH2 domain-binding tetrapeptide mimetics SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID OLEFIN METATHESIS; LIGANDS; DESIGN; ANALOGS; INHIBITORS; PEPTIDES; RECEPTOR; SYSTEMS; AMINES; POTENT AB [GRAPHICS] Ring-closing metathesis (RCM) was employed to join carboxy-terminal alkenyl glycine side chains together with vinyl- and allyl-functionality appended to the P-methylene of amino-terminal phosphotyrosyl (pTyr) mimetics. This required the synthesis of a variety of new pTyr mimetics, including a novel aza-containing analogue. Many of the resulting 15-member macrocyclic tetrapeptide mimetics exhibited low nanomolar Grb2 SH2 domain-binding affinities in spite of the fact that differing ring junction stereochemistries and geometries of the RCM-derived double bond were employed. The finding that significant latitude exists in the structural requirements for ring closure may facilitate the development of therapeutically relevant macrocyle-based Grb2 SH2 domain-binding antagonists. The synthetic approaches used in this study may also find application to peptide mimetics directed at other biological targets. C1 NCI, NIH, Med Chem Lab, CCR, Ft Detrick, MD 21702 USA. SAIC Frederick, Lab Adv Technol Program, Ft Detrick, MD 21702 USA. RP Burke, TR (reprint author), NCI, NIH, Med Chem Lab, CCR, Ft Detrick, MD 21702 USA. EM tburke@helix.nih.gov RI Fisher, Robert/B-1431-2009; Burke, Terrence/N-2601-2014 FU Intramural NIH HHS [Z01 BC006198-18]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 25 TC 9 Z9 9 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD DEC 7 PY 2007 VL 72 IS 25 BP 9635 EP 9642 DI 10.1021/jo701831q PG 8 WC Chemistry, Organic SC Chemistry GA 236OW UT WOS:000251313600028 PM 17990895 ER PT J AU Berg, JM AF Berg, Jeremy M. TI The age-old question of researcher innovation - Response SO SCIENCE LA English DT Letter C1 Natl Inst Gen Med Sci, NIH, Bethesda, MD 20892 USA. RP Berg, JM (reprint author), Natl Inst Gen Med Sci, NIH, Bethesda, MD 20892 USA. OI Berg, Jeremy/0000-0003-3022-0963 NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 7 PY 2007 VL 318 IS 5856 BP 1549 EP 1550 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 238BG UT WOS:000251421700013 ER PT J AU Weir, BA Woo, MS Getz, G Perner, S Ding, L Beroukhim, R Lin, WM Province, MA Kraja, A Johnson, LA Shah, K Sato, M Thomas, RK Barletta, JA Borecki, IB Broderick, S Chang, AC Chiang, DY Chirieac, LR Cho, J Fujii, Y Gazdar, AF Giordano, T Greulich, H Hanna, M Johnson, BE Kris, MG Lash, A Lin, L Lindeman, N Mardis, ER McPherson, JD Minna, JD Morgan, MB Nadel, M Orringer, MB Osborne, JR Ozenberger, B Ramos, AH Robinson, J Roth, JA Rusch, V Sasaki, H Shepherd, F Sougnez, C Spitz, MR Tsao, MS Twomey, D Verhaak, RGW Weinstock, GM Wheeler, DA Winckler, W Yoshizawa, A Yu, SY Zakowski, MF Zhang, QY Beer, DG Wistuba, II Watson, MA Garraway, LA Ladanyi, M Travis, WD Pao, W Rubin, MA Gabriel, SB Gibbs, RA Varmus, HE Wilson, RK Lander, ES Meyerson, M AF Weir, Barbara A. Woo, Michele S. Getz, Gad Perner, Sven Ding, Li Beroukhim, Rameen Lin, William M. Province, Michael A. Kraja, Aldi Johnson, Laura A. Shah, Kinjal Sato, Mitsuo Thomas, Roman K. Barletta, Justine A. Borecki, Ingrid B. Broderick, Stephen Chang, Andrew C. Chiang, Derek Y. Chirieac, Lucian R. Cho, Jeonghee Fujii, Yoshitaka Gazdar, Adi F. Giordano, Thomas Greulich, Heidi Hanna, Megan Johnson, Bruce E. Kris, Mark G. Lash, Alex Lin, Ling Lindeman, Neal Mardis, Elaine R. McPherson, John D. Minna, John D. Morgan, Margaret B. Nadel, Mark Orringer, Mark B. Osborne, John R. Ozenberger, Brad Ramos, Alex H. Robinson, James Roth, Jack A. Rusch, Valerie Sasaki, Hidefumi Shepherd, Frances Sougnez, Carrie Spitz, Margaret R. Tsao, Ming-Sound Twomey, David Verhaak, Roel G. W. Weinstock, George M. Wheeler, David A. Winckler, Wendy Yoshizawa, Akihiko Yu, Soyoung Zakowski, Maureen F. Zhang, Qunyuan Beer, David G. Wistuba, Ignacio I. Watson, Mark A. Garraway, Levi A. Ladanyi, Marc Travis, William D. Pao, William Rubin, Mark A. Gabriel, Stacey B. Gibbs, Richard A. Varmus, Harold E. Wilson, Richard K. Lander, Eric S. Meyerson, Matthew TI Characterizing the cancer genome in lung adenocarcinoma SO NATURE LA English DT Article ID HIGH-RESOLUTION ANALYSIS; TRANSCRIPTION FACTOR-I; COPY-NUMBER; HOMOZYGOUS DELETIONS; LENTIVIRAL VECTOR; SOMATIC MUTATIONS; FREQUENT TARGET; GENE DELIVERY; WIDE ANALYSIS; ARRAY CGH AB Somatic alterations in cellular DNA underlie almost all human cancers(1). The prospect of targeted therapies(2) and the development of high-resolution, genome-wide approaches(3-8) are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize copy-number alterations in primary lung adenocarcinomas. By analysis of a large collection of tumours ( n = 371) using dense single nucleotide polymorphism arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent large-scale copy-number gain or loss, of which only a handful have been linked to a specific gene. We also identify 31 recurrent focal events, including 24 amplifications and 7 homozygous deletions. Only six of these focal events are currently associated with known mutations in lung carcinomas. The most common event, amplification of chromosome 14q13.3, is found in similar to 12% of samples. On the basis of genomic and functional analyses, we identify NKX2-1 ( NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung adenocarcinomas. More generally, our results indicate that many of the genes that are involved in lung adenocarcinoma remain to be discovered. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. Harvard Univ, Canc Program, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Genome Biol Program, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Ulm, Inst Pathol, D-89081 Ulm, Germany. Washington Univ, Genome Sequencing Ctr, St Louis, MO 63130 USA. Washington Univ, Div Stat Genom, St Louis, MO 63130 USA. Washington Univ, Dept Pathol & Immunol, St Louis, MO 63130 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Cologne, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, Max Planck Soc, D-50931 Cologne, Germany. Univ Cologne, Fac Med, D-50931 Cologne, Germany. Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany. Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Dept Computat Biol, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA. Univ Michigan, Thorac Surg Sect, Dept Surg, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Nagoya City Univ, Sch Med, Dept Surg, Nagoya, Aichi 4678602, Japan. Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Univ Hlth Network, Toronto, ON M5G 2C4, Canada. Princess Margaret Hosp, Toronto, ON M5G 2C4, Canada. MIT, Dept Biol, Cambridge, MA 02142 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Sato, MITSUO/I-7280-2014; OI Kris, Mark/0000-0002-7317-5341; Chang, Andrew/0000-0001-9506-0425; Lash, Alex/0000-0003-3787-1590; Rubin, Mark/0000-0002-8321-9950; Giordano, Thomas/0000-0003-0641-8873 FU NCI NIH HHS [F32 CA113126-01A1, F32 CA113126-02, K08 CA122833-01A1, P50 CA070907] NR 40 TC 661 Z9 679 U1 5 U2 43 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 6 PY 2007 VL 450 IS 7171 BP 893 EP U22 DI 10.1038/nature06358 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 237RU UT WOS:000251394900059 PM 17982442 ER PT J AU Ting, CY Herman, T Yonekura, S Gao, S Wang, J Serpe, M O'Connor, MB Zipursky, SL Lee, CH AF Ting, Chun-Yuan Herman, Tory Yonekura, Shinichi Gao, Shuying Wang, Jian Serpe, Mihaela O'Connor, Michael B. Zipursky, S. Lawrence Lee, Chi-Hon TI Tiling of R7 axons in the Drosophila visual system is mediated both by transduction of an activin signal to the nucleus and by mutual repulsion SO NEURON LA English DT Article ID TGF-BETA; TARGET SPECIFICITY; LIPRIN-ALPHA; OPTIC LOBE; C-ELEGANS; GUIDANCE; MELANOGASTER; RECEPTOR; BMP; EXPRESSION AB The organization of neuronal wiring into layers and columns is a common feature of both vertebrate and invertebrate brains. In the Drosophila visual system, each R7 photoreceptor axon projects within a single column to a specific layer of the optic lobe. We refer to the restriction of terminals to single columns as tiling. In a genetic screen based on an R7-dependent behavior, we identified the Activin receptor Baboon and the nuclear import adaptor Importin-alpha 3 as being required to prevent R7 axon terminals from overlapping with the terminals of R7s in neighboring columns. This tiling function requires the Baboon ligand, dActivin, the transcription factor, dSmad2, and retrograde transport from the growth cone to the R7 nucleus. We propose that dActivin is an autocrine signal that restricts R7 growth cone motility, and we demonstrate that it acts in parallel with a paracrine signal that mediates repulsion between R7 terminals. C1 [Herman, Tory] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA. [Ting, Chun-Yuan; Yonekura, Shinichi; Gao, Shuying; Lee, Chi-Hon] NICHHD, Unit Neuronal Connect, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20817 USA. [Wang, Jian] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA. [Serpe, Mihaela; O'Connor, Michael B.] Univ Minnesota, Howard Hughes Med Inst, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [Zipursky, S. Lawrence] Univ Calif Los Angeles, Los Angeles Sch Med, Howard Hughes Med Inst, Dept Biol Chem, Los Angeles, CA 90095 USA. RP Herman, T (reprint author), Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA. EM herman@molbio.uoregon.edu; leechih@mail.nih.gov RI Gao, Shuying/D-8183-2011; Lee, Chi-Hon/G-9190-2012; Ting, chun-yuan/F-6448-2013; OI O'Connor, Michael/0000-0002-3067-5506 FU Howard Hughes Medical Institute; Intramural NIH HHS [Z01 HD008748-06]; NICHD NIH HHS [HD008748-03, Z01 HD008748] NR 53 TC 54 Z9 54 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 6 PY 2007 VL 56 IS 5 BP 793 EP 806 DI 10.1016/j.neuron.2007.09.033 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 241MA UT WOS:000251659300007 PM 18054857 ER PT J AU Jin, W Yun, C Kwak, MK Kim, TA Kim, SJ AF Jin, W. Yun, C. Kwak, M-K Kim, T-A Kim, S-J TI TrkC binds to the type II TGF-beta receptor to suppress TGF-beta signaling SO ONCOGENE LA English DT Article DE neurotrophin receptors; TrkC; TGF-beta; cancer; signaling; ETV6-NTRK3 ID ETV6-NTRK3 GENE FUSION; GASTRIC-CANCER CELLS; HUMAN NEUROBLASTOMAS; EXPRESSION; TUMORS; NEUROTROPHINS; INHIBITOR; PROGNOSIS; PROSTATE; COMPLEX AB Growing evidence suggests that overexpression of TrkC, a member of the Trk family of neurotrophin receptors, could drive tumorigenesis, invasion and metastatic capability in cancer cells. However, relatively little is known about the mechanism of TrkC-mediated oncogenesis. The TrkC gene is a partner of the Tel-TrkC (ETV6-NTRK3) chimeric tyrosine kinase, a potent oncoprotein expressed in tumors derived from multiple cell lineages. Recently, we have shown that ETV6-NTRK3 suppresses transforming growth factor-beta (TGF-beta) signaling by directly binding to the type II TGF-beta receptor (TbRII). Here, we report that expression of TrkC also suppresses TGF-beta-induced Smad2/3 phosphorylation and transcriptional activation. Silencing TrkC expression by small interfering RNA in the highly metastatic 4T1 mammary tumor cell line expressing endogenous TrkC significantly enhanced TGF-beta-induced Smad2/3 phosphorylation and restored TGF-b growth inhibitory activity. In contrast, expression of TrkC in 67NR cells, in which TrkC is not expressed, suppressed TGF-beta transcriptional activation. Moreover, we show that TrkC directly binds to the TbRII, thereby preventing it from interacting with the type I TGF-beta receptor (T beta RI). These results indicate that TrkC is an inhibitor of TGF-beta tumor suppressor activity. C1 [Jin, W.; Yun, C.; Kwak, M-K; Kim, T-A; Kim, S-J] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Kim, S-J] Gachon Univ Med & Sci, Lee Gil Ya Canc & Diabet Inst, Lab Cell Regulat & Carcinogenesis, Inchon, South Korea. RP Kim, SJ (reprint author), NCI, Lab Canc Biol & Genet, NIH, Bldg 37,Room 5046D,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kims@mail.nih.gov FU Intramural NIH HHS NR 32 TC 14 Z9 14 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 6 PY 2007 VL 26 IS 55 BP 7684 EP 7691 DI 10.1038/sj.onc.1210571 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 239SK UT WOS:000251537800010 PM 17546043 ER PT J AU Mazzone, L Ducci, F Scoto, MC Passaniti, E D'Arrigo, VG Vitiello, B AF Mazzone, Luigi Ducci, Francesca Scoto, Maria Cristina Passaniti, Eleonora D'Arrigo, Valentina Genitori Vitiello, Benedetto TI The role of anxiety symptoms in school performance in a community sample of children and adolescents SO BMC PUBLIC HEALTH LA English DT Article ID PSYCHIATRIC-DISORDERS; DEPRESSIVE SYMPTOMS; LEARNING-DISABILITIES; GENDER-DIFFERENCES; CHILDHOOD ANXIETY; FOLLOW-UP; PREVALENCE; RISK; COMORBIDITY; REFUSAL AB Background: Anxiety symptoms are relatively common among children and adolescents and can interfere with functioning. The prevalence of anxiety and the relationship between anxiety and school performance were examined among elementary, middle, and high school students. Methods: Samples of elementary (N = 131, age 8-10 years), middle (N = 267, age 11 - 13 years), and high school (N = 80, age 14-16 years) children were recruited from four public schools in a predominantly middle-class community in Catania, Italy. Children completed the Multidimensional Anxiety Scale for Children (MASC). T-scores were computed for the MASC total scores, and considered to be in the anxious range if 65 or above. Current academic grades were obtained from school records. Results: Of the 478 children, 35 (7.3%) had a MASC T-score in the anxious range. The rate of children in the anxious range was 2.3% in elementary, 7.9% in middle, and 15.9% in high school (chi(2) = 7.8, df = 2, p < 0.05), and was 14.1% among students with insufficient grades, 9.4% among those with sufficient grades, and 3.9% among those with good or very good grades (chi(2) = 11.68, df = 2, p < 0.01). Conclusion: In this community sample of children and adolescents attending elementary through high school, the prevalence of abnormally high self-reported levels of anxiety increased in frequency with age and was negatively associated with school performance. C1 [Mazzone, Luigi; Scoto, Maria Cristina; Passaniti, Eleonora; D'Arrigo, Valentina Genitori] Univ Catania, Dept Pediat, Div Child Neurol & Psychiat, Catania, Italy. [Ducci, Francesca] Univ Pisa, Dept Psychiat, Pisa, Italy. [Vitiello, Benedetto] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Mazzone, L (reprint author), Univ Catania, Dept Pediat, Div Child Neurol & Psychiat, Catania, Italy. EM gigimazzone@yahoo.it; francescaducci@yahoo.com; crillajo@yahoo.it; eleonorapass@supereva.it; valentina.genitori@libero.it; bvitiell@mail.nih.gov NR 43 TC 23 Z9 23 U1 7 U2 26 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD DEC 5 PY 2007 VL 7 AR 347 DI 10.1186/1471-2458-7-347 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 261BU UT WOS:000253054900001 PM 18053257 ER PT J AU Drgonova, J Liu, QR Hall, FS Krieger, RM Uhl, GR AF Drgonova, Jana Liu, Qing-Rong Hall, F. Scott Krieger, Rachael M. Uhl, George R. TI Deletion of v7-3 (SLC6A15) transporter allows assessment of its roles in synaptosomal proline uptake, leucine uptake and behaviors SO BRAIN RESEARCH LA English DT Article DE v7-3 knockout; orphan neurotransmitter transporter; B degrees AT2; SBAT1 ID CENTRAL-NERVOUS-SYSTEM; SENSITIVE DOPAMINE TRANSPORTER; NEUROTRANSMITTER TRANSPORTER; RAT-BRAIN; ORPHAN TRANSPORTER; MOLECULAR-CLONING; FUNCTIONAL-CHARACTERIZATION; HIPPOCAMPAL-NEURONS; SYNAPTIC VESICLES; MAMMALIAN BRAIN AB v7-3 (SLC6A15) is the prototype fora gene subfamily whose members have sequence homologies to classical Na(+)- and Cl(-)-dependent neurotransmitter transporters but display unusual features that include characteristic large fourth extracellular loops. Interest in v7-3 has been increased by the elucidation of its expression in neurons located in cerebral cortex, hippocampus, cerebellum, midbrain and olfactory bulb. To help clarify the role of v7-3 in brain functions, we have created and characterized v7-3 knockout mice. These mice lack functional v7-3 protein but are viable and fertile. While our studies were in progress, v7-3 expression was reported to confer transport of proline and branched-chain amino acids in in vitro expression systems [Takanaga, H., Mackenzie, B., Peng, J.B., Hediger, M.A., 2005b. Characterization of a branched-chain aminoacid transporter SBAT1 (SLC6A15) that is expressed in human brain. Biochem. Biophys. Res. Commun. 337,892-900; Broer, A., Tietze, N., Kowalczuk, S., Chubb, S., Munzinger, M., Bak, L.K., Broer, S., 2006. The orphan transporter v7-3 (slc6a15) is a Ne-dependent neutral amino acid transporter (BOAT2). Biochem. J. 393, 421-430]. Assessment of amino acid uptake into cortical synaptosomes of v7-3 knockouts identified 15% and 40% reductions in sodium-dependent proline and leucine transport, respectively, compared to wild type controls. Despite these biochemical changes, v7-3 knockout mice demonstrate only modest alterations in rotarod performance with aging and lack reproducible alterations in other motor, memory, anxiety or olfactory tests. Compensation for the lack of v7-3 via other amino acid carriers is likely to leave v7-3 knockouts without gross behavioral manifestations. The current results place v7-3 in the context of other brain transporters that accumulate proline and branched-chain amino acids. (c) 2007 Elsevier B.V. All rights reserved. C1 [Drgonova, Jana; Liu, Qing-Rong; Hall, F. Scott; Krieger, Rachael M.; Uhl, George R.] NIDA, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Drgonova, Jana/B-2903-2008; Liu, Qing-Rong/A-3059-2012; Hall, Frank/C-3036-2013; OI Liu, Qing-Rong/0000-0001-8477-6452; Hall, Frank/0000-0002-0822-4063; Drgonova, Jana/0000-0002-4623-8466 FU Intramural NIH HHS [Z01 DA000165-12] NR 42 TC 12 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 5 PY 2007 VL 1183 BP 10 EP 20 DI 10.1016/j.brainres.2007.09.001 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 244NC UT WOS:000251871600002 PM 17931606 ER PT J AU Tan, HY Chen, Q Goldberg, TE Mattay, VS Meyer-Lindenberg, A Weinberger, DR Callicott, JH AF Tan, Hao-Yang Chen, Qiang Goldberg, Terry E. Mattay, Venkata S. Meyer-Lindenberg, Andreas Weinberger, Daniel R. Callicott, Joseph H. TI Catechol-O-methyltransferase Val158Met modulation of prefrontal-parietal-striatal brain systems during arithmetic and temporal transformations in working memory SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cerebral cortex; executive cognition; dopamine; fMRI; dopamine; genetics ID VAL(108/158) MET GENOTYPE; EVENT-RELATED FMRI; BASAL GANGLIA; DOPAMINE MODULATION; GENETIC-VARIATION; COMT GENOTYPE; SCHIZOPHRENIA; CORTEX; MAINTENANCE; INHIBITION AB Working memory (WM) is critically mediated by dopaminergic tuning of signal-to-noise in cortical neural assemblies. However, little is known about the distributed neuronal networks impacted by dopaminergic modulation in the component processes of WM. Here, we used the genotype of the Val158Met polymorphism in catechol-O-methyltransferase ( COMT) as an index of relative cortical dopamine bioavailability and tuning efficiency, to examine the spatial and subprocess specificity by which dopaminergic modulation occurs within the prefrontal-parietal-striatal network during WM, thus empirically showing that dopamine plays key roles in updating and stabilizing new information at the neural systems level. In an event-related fMRI task dissociating component numerical WM subprocesses, baseline numerical size comparison engaged ventrolateral prefrontal cortical activation that correlated with COMT Val-allele load (COMT Val > Met), while performing arithmetic transformations further engaged this genotype effect in dorsolateral prefrontal cortex (DLPFC), as well as in parietal and striatal regions. Critically, additional temporal integration of information in WM disproportionately engaged greater COMT Val > Met effects only at DLPFC. COMT Val > Met effects were also observed in DLPFC during encoding of new information into WM, but not at its subsequent retrieval. Thus, temporal updating operations, but less so the retrieval of already encoded representations, engaged relatively specific dopaminergic tuning at the DLPFC. Manipulating and rapidly updating representations were sensitive to dopaminergic modulation of neural signaling in a larger prefrontal-parietal-striatal network. These findings add to the integration of dopaminergic signaling in basic cortical assemblies with their roles in specific human brain networks during the orchestration of information processing in WM. C1 [Tan, Hao-Yang; Chen, Qiang; Mattay, Venkata S.; Meyer-Lindenberg, Andreas; Weinberger, Daniel R.; Callicott, Joseph H.] NIMH, Unit Dynam Imaging Genet, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,NIH, Bethesda, MD 20892 USA. [Goldberg, Terry E.] Zucker Hillside Hosp, Psychiat Res Div, Glen Oaks, NY 11004 USA. RP Tan, HY (reprint author), NIMH, Unit Dynam Imaging Genet, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,NIH, 10 Ctr Dr,Room 4C-216, Bethesda, MD 20892 USA. EM tanh@mail.nih.gov; callicottj@mail.nih.gov RI Callicott, Joseph/C-9102-2009; Meyer-Lindenberg, Andreas/H-1076-2011 OI Callicott, Joseph/0000-0003-1298-3334; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU Intramural NIH HHS NR 52 TC 96 Z9 97 U1 0 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 5 PY 2007 VL 27 IS 49 BP 13393 EP 13401 DI 10.1523/JNEUROSC.4041-07.2007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 240VI UT WOS:000251615900006 PM 18057197 ER PT J AU Kim, EJ Amorelli, B Abdo, M Thomas, CJ Love, DC Knapp, S Hanover, JA AF Kim, Eun J. Amorelli, Benjamin Abdo, Mohannad Thomas, Craig J. Love, Dona C. Knapp, Spencer Hanover, John A. TI Distinctive inhibition of O-GlcNAcase isoforms by an alpha-GlcNAc thiolsulfonate SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID BETA-N-ACETYLGLUCOSAMINIDASE; STRUCTURAL INSIGHTS; PROTEIN; GLYCOSYLATION; SUBSTRATE; REAGENTS; NUCLEAR; MGEA5 AB O-GlcNAcase (OGA) promotes O -GlcNAc removal, and thereby plays a key role in O-GlcNAc metabolism, a feature of a variety of vital cellular processes. Two splice transcripts of human OGA encode "long OGA", which contains a distinct N-terminal O -GlcNAcase domain and a C-terminal histoneacetylferase (HAT) domain, and "short OGA", which lacks the HAT domain. The functional roles of long OGA are only beginning to be unraveled, and the characteristics of short OGA remain almost unknown. We find that short OGA, which possesses O -GlcNAcase catalysis machinery like that of long OGA, exhibits comparative resistance to previously described potent inhibitors of long OGA and lysosomal hexosaminidases, including PUGNAc and NAG-thiazoline, suggesting a role for the HAT domain in O -GlcNAcase catalysis. We also find that alpha-GlcNAc thiolsulfonate (2) is the most potent inhibitor of short OGA yet described (K-i = 10 mu M), and exhibits some degree of selectivity versus long OGA and lysosomal hexosaminidases. In contrast to its mode of inhibition of short OGA, 2 acts as a irreversible inhibitor of long OGA by covalently modifying the enzyme as an S-GlcNAc derivative. Covalent attachment of GlcNAc to the HAT domain of long OGA dramatically changes its properties with respect to enzymatic activity and caspase-3 cleavage. C1 NIH, NIDDK, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. NIH, NHGRI, Chem Genom Ctr, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIH, NIDDK, Lab Cell Biochem & Biol, Bldg 10, Bethesda, MD 20892 USA. EM jah@helix.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [AI055760] NR 19 TC 20 Z9 20 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 5 PY 2007 VL 129 IS 48 BP 14854 EP + DI 10.1021/ja076038u PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 236HK UT WOS:000251293500011 PM 17994748 ER PT J AU Rhim, JH Tosato, G AF Rhim, Jung Hyo Tosato, Giovanna TI Targeting the tumor vasculature to improve the efficacy of oncolytic virus therapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID INTEGRIN ALPHA(V)BETA(3); IMMUNE-RESPONSES; CELL ATTACHMENT; TNF-ALPHA; CANCER; ANGIOGENESIS; INFLAMMATION; FIBRONECTIN; PEPTIDE; VITRONECTIN C1 NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), Bldg 37,Rm 4124, Bethesda, MD 20892 USA. EM tosatog@mail.nih.gov NR 38 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 5 PY 2007 VL 99 IS 23 BP 1739 EP 1741 DI 10.1093/jnci/djm234 PG 3 WC Oncology SC Oncology GA 239VE UT WOS:000251545600001 PM 18042930 ER PT J AU Giaccone, G AF Giaccone, Giuseppe TI (18)Fluorodeoxyglucose positron emission tomography, a standard diagnostic tool in lung cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PET/CT; MANAGEMENT; NODULES; TRIAL C1 NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 13 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 5 PY 2007 VL 99 IS 23 BP 1741 EP 1743 DI 10.1093/jnci/djm245 PG 3 WC Oncology SC Oncology GA 239VE UT WOS:000251545600002 PM 18042929 ER PT J AU Gail, MH Costantino, JP Pee, D Bondy, M Newman, L Selvan, M Anderson, GL Malone, KE Marchbanks, PA McCaskill-Stevens, W Norman, SA Simon, MS Spirtas, R Ursin, G Bernstein, L AF Gail, Mitchell H. Costantino, Joseph P. Pee, David Bondy, Melissa Newman, Lisa Selvan, Mano Anderson, Garnet L. Malone, Kathleen E. Marchbanks, Polly A. McCaskill-Stevens, Worta Norman, Sandra A. Simon, Michael S. Spirtas, Robert Ursin, Giske Bernstein, Leslie TI Projecting individualized absolute invasive breast cancer risk in African American women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID REPRODUCTIVE EXPERIENCES; ATTRIBUTABLE RISK; WHITE; VALIDATION; PREDICTION; MODELS AB Background The Breast Cancer Risk Assessment Tool of the National Cancer Institute (NCI) is widely used for counseling and determining eligibility for breast cancer prevention trials, although its validity for projecting risk in African American women is uncertain. We developed a model for projecting absolute risk of invasive breast cancer in African American women and compared its projections with those from the Breast Cancer Risk Assessment Tool. Methods Data from 1607 African American women with invasive breast cancer and 1647 African American control subjects in the Women's Contraceptive and Reproductive Experiences (CARE) Study were used to compute relative and attributable risks that were based on age at menarche, number of affected mother or sisters, and number of previous benign biopsy examinations. Absolute risks were obtained by combining this information with data on invasive breast cancer incidence in African American women from the NCI's Surveillance, Epidemiology and End Results Program and with national mortality data. Eligibility screening data from the Study of Tamoxifen and Raloxifene (STAR) trial were used to determine how the new model would affect eligibility, and independent data from the Women's Health Initiative (WHI) were used to assess how well numbers of invasive breast cancers predicted by the new model agreed with observed cancers. Results Tables and graphs for estimating relative risks and projecting absolute invasive breast cancer risk with confidence intervals were developed for African American women. Relative risks for family history and number of biopsies and attributable risks estimated from the CARE population were lower than those from the Breast Cancer Risk Assessment Tool, as was the discriminatory accuracy (i.e., concordance). Using eligibility screening data from the STAR trial, we estimated that 30.3% of African American women would have had 5-year invasive breast cancer risks of at least 1.66% by use of the CARE model, compared with only 14.5% by use of the Breast Cancer Risk Assessment Tool. The numbers of cancers predicted by the CARE model agreed well with observed numbers of cancers (i.e., it was well calibrated) in data from the WHI, except that it underestimated risk in African American women with breast biopsy examinations. Conclusions The CARE model usually gave higher risk estimates for African American women than the Breast Cancer Risk Assessment Tool and is recommended for counseling African American women regarding their risk of breast cancer. C1 Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. Womens Hlth Initiat Clin Coordinating Ctr, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Informat Management Serv Inc, Rockville, MD USA. Wayne State Univ, Div Hematol & Oncol, Karmanos Canc Inst, Detroit, MI USA. Univ Michigan, Breast Care Ctr, Ann Arbor, MI 48109 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NICHHD, Contracept & Reprod Branch, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Norris Comprehens Canc Med, Los Angeles, CA USA. Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA. Univ Texas MD Anderson Canc Ctr, Dept Clin Effectiveness, Houston, TX USA. RP Gail, MH (reprint author), NCI, Div Canc Epidemiol & Genet, Execut Plaza S Rm 8032, Bethesda, MD 20892 USA. EM gailm@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [U10-CA-37377, U10-CA-69974, U10CA-12027, U10CA-69651]; NICHD NIH HHS [N01-HD-2-3168, N01-HD-2-3166, N01-HD-3-3174, N01-HD-3-3175, N01-HD-3-3176, Y01-HD-7022] NR 18 TC 122 Z9 125 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 5 PY 2007 VL 99 IS 23 BP 1782 EP 1792 DI 10.1093/jnci/djm223 PG 11 WC Oncology SC Oncology GA 239VE UT WOS:000251545600010 PM 18042936 ER PT J AU Glass, AG Lacey, JV Carreon, JD Hoover, RN AF Glass, Andrew G. Lacey, James V., Jr. Carreon, Joseph D. Hoover, Robert N. TI Re: Breast cancer incidence, 1980-2006: Combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Glass, Andrew G.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR 97227 USA. [Lacey, James V., Jr.; Carreon, Joseph D.; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Glass, AG (reprint author), Kaiser Permanente NW, Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA. EM andrew.glass@kpchr.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 5 PY 2007 VL 99 IS 23 BP 1819 EP 1819 DI 10.1093/jnci/djm226 PG 1 WC Oncology SC Oncology GA 239VE UT WOS:000251545600018 ER PT J AU Boyd, WA McBride, SJ Freedman, JH AF Boyd, Windy A. McBride, Sandra J. Freedman, Jonathan H. TI Effects of Genetic Mutations and Chemical Exposures on Caenorhabditis elegans Feeding: Evaluation of a Novel, High-Throughput Screening Assay SO PLOS ONE LA English DT Article AB Background. Government agencies have defined a need to reduce, refine or replace current mammalian-based bioassays with testing methods that use alternative species. Invertebrate species, such as Caenorhabditis elegans, provide an attractive option because of their short life cycles, inexpensive maintenance, and high degree of evolutionary conservation with higher eukaryotes. The C. elegans pharynx is a favorable model for studying neuromuscular function, and the effects of chemicals on neuromuscular activity, i.e., feeding. Current feeding methodologies, however, are labor intensive and only semi-quantitative. Methodology/Principal Findings. Here a high-throughput assay is described that uses flow cytometry to measure C. elegans feeding by determining the size and intestinal fluorescence of hundreds of nematodes after exposure to fluorescent-labeled microspheres. This assay was validated by quantifying fluorescence in feeding-defective C. elegans ( eat mutants), and by exposing wild-type nematodes to the neuroactive compounds, serotonin and arecoline. The eat mutations previously determined to cause slow pumping rates exhibited the lowest feeding levels with our assay. Concentration-dependent increases in feeding levels after serotonin exposures were dependent on food availability, while feeding levels decreased in arecoline-exposed nematodes regardless of the presence of food. The effects of the environmental contaminants, cadmium chloride and chlorpyrifos, on wild-type C. elegans feeding were then used to demonstrate an application of the feeding assay. Cadmium exposures above 200 mu M led to a sharp drop in feeding levels. Feeding of chlorpyrifos-exposed nematodes decreased in a concentration-dependent fashion with an EC(50) of 2 mu M. Conclusions/Significance. The C. elegans fluorescence microsphere feeding assay is a rapid, reliable method for the assessment of neurotoxic effects of pharmaceutical drugs, industrial chemicals or environmental agents. This assay may also be applicable to large scale genetic or RNAi screens used to identify genes that are necessary for the development or function of the pharynx or other neuromuscular systems. C1 [Boyd, Windy A.; Freedman, Jonathan H.] NIEHS, Mol Toxicol Lab, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [McBride, Sandra J.; Freedman, Jonathan H.] Duke Univ, Nicholas Sch Environm & Earth Sci, Durham, NC USA. RP Freedman, JH (reprint author), NIEHS, Mol Toxicol Lab, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. EM freedma1@niehs.nih.gov OI Boyd, Windy/0000-0003-3803-3716 FU National Toxicology Program; Intramural Research Program of the NIH; NIEHS; NIH National Center for Research Resources (NCRR). FX This work was supported ( in part) by the National Toxicology Program, and by the Intramural Research Program of the NIH, and NIEHS. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources (NCRR). NR 47 TC 30 Z9 38 U1 2 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 5 PY 2007 VL 2 IS 12 AR e1259 DI 10.1371/journal.pone.0001259 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JD UT WOS:000207459400008 PM 18060055 ER PT J AU Gwinn, K Corriveau, RA Mitsumoto, H Bednarz, K Brown, RH Cudkowicz, M Gordon, PH Hardy, J Kasarskis, EJ Kaufmann, P Miller, R Sorenson, E Tandan, R Traynor, BJ Nash, J Sherman, A Mailman, MD Ostell, J Bruijn, L Cwik, V Rich, SS Singleton, A Refolo, L Andrews, J Zhang, R Conwit, R Keller, MA AF Gwinn, Katrina Corriveau, Roderick A. Mitsumoto, Hiroshi Bednarz, Kate Brown, Robert H., Jr. Cudkowicz, Merit Gordon, Paul H. Hardy, John Kasarskis, Edward J. Kaufmann, Petra Miller, Robert Sorenson, Eric Tandan, Rup Traynor, Bryan J. Nash, Josefina Sherman, Alex Mailman, Matthew D. Ostell, James Bruijn, Lucie Cwik, Valerie Rich, Stephen S. Singleton, Andrew Refolo, Larry Andrews, Jaime Zhang, Ran Conwit, Robin Keller, Margaret A. CA ALS Res Grp TI Amyotrophic Lateral Sclerosis: An Emerging Era of Collaborative Gene Discovery SO PLOS ONE LA English DT Article AB Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered. However, most forms of the disease are not obviously familial. Recent advances in human genetics have enabled genome-wide analyses of single nucleotide polymorphisms ( SNPs) that make it possible to study complex genetic contributions to human disease. Genome-wide SNP analyses require a large sample size and thus depend upon collaborative efforts to collect and manage the biological samples and corresponding data. Public availability of biological samples ( such as DNA), phenotypic and genotypic data further enhances research endeavors. Here we discuss a large collaboration among academic investigators, government, and non-government organizations which has created a public repository of human DNA, immortalized cell lines, and clinical data to further gene discovery in ALS. This resource currently maintains samples and associated phenotypic data from 2332 MND subjects and 4692 controls. This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS. C1 [Gwinn, Katrina; Refolo, Larry; Zhang, Ran; Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA. [Corriveau, Roderick A.; Nash, Josefina; Andrews, Jaime; Keller, Margaret A.] Coriell Inst Med Res, Camden, NJ USA. [Mitsumoto, Hiroshi; Bednarz, Kate; Gordon, Paul H.; Kaufmann, Petra] Columbia Univ, Eleanor & Lou Gehrig MDA ALS Res Ctr, New York, NY USA. [Brown, Robert H., Jr.; Cudkowicz, Merit; Sherman, Alex] Massachusetts Gen Hosp, Charlestown, MA USA. [Hardy, John; Singleton, Andrew] NIA, NIH, Bethesda, MD 20892 USA. [Kasarskis, Edward J.] Univ Kentucky, Lexington, KY USA. [Miller, Robert] Calif Pacific Med Ctr, San Francisco, CA USA. [Sorenson, Eric] Mayo Med Ctr, Rochester, MN USA. [Tandan, Rup] Univ Vermont, Burlington, VT USA. [Traynor, Bryan J.] NIMH, NIH, Bethesda, MD 20892 USA. [Mailman, Matthew D.; Ostell, James] NIH, Natl Ctr Bioinformat, Bethesda, MD 20892 USA. [Bruijn, Lucie] ALS Assoc, Calabasas Hills, CA USA. [Cwik, Valerie] Muscular Dystrophy Assoc, Tucson, AZ USA. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. RP Gwinn, K (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM GwinnK@ninds.nih.gov RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Traynor, Bryan/G-5690-2010; OI Thakore, Nimish/0000-0003-3418-3362; Carter, Gregory/0000-0001-7617-4750; Gwinn, Katrina/0000-0002-8277-651X FU NINDS [N01-NS-2-2349, NOT-03-016, R01 NS049640-01, R01 NS045294-01, R01 NS045087-01, R01 NS048125-01, R01 NS044887-01, R01 NS042759-01]; ALS Association; NIA Intramural Laboratory of Neurogenetics; NIMH Intramural; NIH [RR-00109]; NCBI dbGaP FX The work described herein was created with funding by NINDS (RAC, JN, JA, MK, Repository, Contract NINDS N01-NS-2-2349, NINDS Supplement Notice NOT-03-016), The ALS Association, NINDS R01 grants (RHB, R01 NS049640-01; MC, R01 NS049640-01; PHG R01 NS045294-01; EK R01 NS045087-01; PK R01 NS048125-01; RM R01 NS044887-01; ES R01 NS042759-01), NIA Intramural Laboratory of Neurogenetics, (JH, AS), NIMH Intramural (BT), NIH RR-00109 ( RT), and NCBI dbGaP ( http://www.ncbi.nlm.nih.gov/sites/entrez?db = gap). NR 47 TC 10 Z9 10 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 5 PY 2007 VL 2 IS 12 AR e1254 DI 10.1371/journal.pone.0001254 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JD UT WOS:000207459400003 PM 18060051 ER PT J AU McClintock, D Ratner, D Lokuge, M Owens, DM Gordon, LB Collins, FS Djabali, K AF McClintock, Dayle Ratner, Desiree Lokuge, Meepa Owens, David M. Gordon, Leslie B. Collins, Francis S. Djabali, Karima TI The Mutant Form of Lamin A that Causes Hutchinson-Gilford Progeria Is a Biomarker of Cellular Aging in Human Skin SO PLOS ONE LA English DT Article AB Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare disorder characterized by accelerated aging and early death, frequently from stroke or coronary artery disease. 90% of HGPS cases carry the LMNA G608G (GGC>GGT) mutation within exon 11 of LMNA, activating a splice donor site that results in production of a dominant negative form of lamin A protein, denoted progerin. Screening 150 skin biopsies from unaffected individuals ( newborn to 97 years) showed that a similar splicing event occurs in vivo at a low level in the skin at all ages. While progerin mRNA remains low, the protein accumulates in the skin with age in a subset of dermal fibroblasts and in a few terminally differentiated keratinocytes. Progerin-positive fibroblasts localize near the basement membrane and in the papillary dermis of young adult skin; however, their numbers increase and their distribution reaches the deep reticular dermis in elderly skin. Our findings demonstrate that progerin expression is a biomarker of normal cellular aging and may potentially be linked to terminal differentiation and senescence in elderly individuals. C1 [McClintock, Dayle; Ratner, Desiree; Lokuge, Meepa; Owens, David M.; Djabali, Karima] Columbia Univ, Coll Phys & Surg, Dept Dermatol, New York, NY 10027 USA. [Owens, David M.] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. [Gordon, Leslie B.] Brown Univ, Dept BioMed Pediat, Providence, RI 02912 USA. [Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Djabali, K (reprint author), Columbia Univ, Coll Phys & Surg, Dept Dermatol, New York, NY 10027 USA. EM kd206@columbia.edu FU Progeria Research Foundation; Irving Foundation; NIH [K01AR048594, RO1AG025302, NCI R01CA114010]; National Human Genome Research Institute FX This work was supported by The Progeria Research Foundation, The Irving Foundation, and NIH Grants K01AR048594 and RO1AG025302 (to KD), NCI R01CA114010 (to DMO), and from the intramural program of the National Human Genome Research Institute (to FSC). NR 51 TC 135 Z9 139 U1 2 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD DEC 5 PY 2007 VL 2 IS 12 AR e1269 DI 10.1371/journal.pone.0001269 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JD UT WOS:000207459400016 PM 18060063 ER PT J AU Steel, JC Morrison, BJ Mannan, P Abu-Asab, MS Wildner, O Miles, BK Yim, KC Ramanan, V Prince, GA Morris, JC AF Steel, Jason C. Morrison, Brian J. Mannan, Poonarn Abu-Asab, Mones S. Wildner, Oliver Miles, Brian K. Yim, Kevin C. Ramanan, Vijay Prince, Gregory A. Morris, John C. TI Immunocompetent syngeneic cotton rat tumor models for the assessment of replication-competent oncolytic adenovirus SO VIROLOGY LA English DT Article DE replicating adenovirus; cotton rat; oncolysis; virotherapy; cancer ID PHASE-I TRIAL; RECURRENT PROSTATE-CANCER; SUICIDE GENE-THERAPY; ANIMAL-MODEL; SIGMODON-HISPIDUS; DENDRITIC CELLS; VECTORS; VIRUSES; PATHOGENICITY; PATHOGENESIS AB oncolytic adenoviruses as a treatment for cancer have demonstrated limited clinical activity. Contributing to this may be the relevance of preclinical animal models used to study these agents. Syngeneic mouse tumor models are generally non-permissive for adenoviral replication, whereas human tumor xenograft models exhibit attenuated immune responses to the vector. The cotton rat (Sigmodon hispidus) is susceptible to human adenovirus infection, permissive for viral replication and exhibits similar inflammatory pathology to humans with adenovirus replicating in the lungs, respiratory passages and cornea. We evaluated three transplantable tumorigenic cotton rat cell lines, CCRT, LCRT and VCRT as models for the study of oncolytic adenoviruses. All three cells lines were readily infected with adenovirus type-5-based vectors and exhibited high levels of transgene expression. The cell lines supported viral replication demonstrated by the induction of cytopathogenic effect (CPE) in tissue culture, increase in virus particle numbers and assembly of virions seen on transmission electron microscopy. In vivo, LCRT and VCRT tumors demonstrated delayed growth after injection with replicating adenovirus. No in vivo antitumor activity was seen in CCRT tumors despite in vitro oncolysis. Adenovirus was also rapidly cleared from the CCRT tumors compared to LCRT and VCRT tumors. The effect observed with the different cotton rat tumor cell lines mimics the variable results of human clinical trials highlighting the potential relevance of this model for assessing the activity and toxicity of oncolytic adenoviruses. C1 NCI, Canc Gene Therapy Sect, Metab Branch, Ctr Canc Res,Mark O Hatfield Clin Res Ctr,NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Virion Syst Inc, Rockville, MD USA. Ruhr Univ Bochum, Dept Mol & Med Virol, Bochum, Germany. RP Morris, JC (reprint author), NCI, Canc Gene Therapy Sect, Metab Branch, Ctr Canc Res,Mark O Hatfield Clin Res Ctr,NIH, Room 4-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM jmorris@mail.nih.gov RI Steel, Jason/D-1805-2013; OI Steel, Jason/0000-0003-3608-7542; Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [NIH0010047277, Z99 CA999999] NR 39 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 5 PY 2007 VL 369 IS 1 BP 131 EP 142 DI 10.1016/j.virol.2007.07.022 PG 12 WC Virology SC Virology GA 232LW UT WOS:000251022200012 PM 17727912 ER PT J AU Lai, L Vodros, D Kozlowski, PA Montefiori, DC Wilson, RL Akerstrom, VL Chennareddi, L Yu, T Kannanganat, S Ofielu, L Villinger, F Wyatt, LS Moss, B Amara, RR Robinson, HL AF Lai, Lilin Vodros, Dalma Kozlowski, Pamela A. Montefiori, David C. Wilson, Robert L. Akerstrom, Vicki L. Chennareddi, Lakshmi Yu, Tianwei Kannanganat, Sunil Ofielu, Lazarus Villinger, Francois Wyatt, Linda S. Moss, Bernard Amara, Rama Rao Robinson, Harriet L. TI GM-CSF DNA: An adjuvant for higher avidity IgG, rectal IgA, and increased protection against the acute phase of a SHIV-89.6P challenge by a DNA/MVA immunodeficiency virus vaccine SO VIROLOGY LA English DT Article DE immunodeficiency virus; vaccine; GM-CSF adjuvant; ab avidity; rectal IgA ID COLONY-STIMULATING FACTOR; HUMORAL IMMUNE-RESPONSES; T-CELL RESPONSES; DENDRITIC CELLS; RHESUS-MONKEYS; IN-VIVO; DISEASE PROGRESSION; ANTIBODY-RESPONSES; HIV-1 INFECTION; MUCOSAL AB Single intradermal or intramuscular inoculations of GM-CSF DNA with the DNA prime for a simian-human immunodeficiency virus (SHIV)-89.6 vaccine, which consists of DNA priming followed by modified vaccinia Ankara (MVA) boosting, increased protection of both the blood and intestines against the acute phase of an intrarectal SHIV-89.6P challenge. GM-CSF appeared to contribute to protection by enhancing two antibody responses: the avidity maturation of anti-Env IgG in blood (p=<0.01) and the presence of long lasting anti-viral IgA in rectal secretions (p<0.01). The avidity of anti-Env IgG showed strong correlations with protection both pre and post challenge. Animals with the highest avidity anti-Env Ab had 1000-fold reductions in peak viremia over those with the lowest avidity anti-Env Ab. The enhanced IgA response was associated with the best protection, but did not achieve significance. (C) 2007 Elsevier Inc. All rights reserved. C1 Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. Emory Vaccine Ctr, Atlanta, GA 30322 USA. LSUHSC, Gene Therapy Program, New Orleans, LA 70112 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Robinson, HL (reprint author), Yerkes Natl Primate Res Ctr, 954 Gatewood Rd, Atlanta, GA 30329 USA. EM hrobins@rmy.emory.edu FU NCRR NIH HHS [P51 RR000165, P51 RR000165-436437, P51 RR000165-440145, P51 RR000165-450145, P51 RR000165-465277, P51 RR00165]; NIAID NIH HHS [N01AI30034, AI 30034, P01 AI 49364, P01 AI049364, P01 AI049364-01, P01 AI049364-02, P01 AI049364-03, P01 AI049364-04, P01 AI049364-05, R01 AI 58896, R01 AI058896, R01 AI058896-04]; NIDA NIH HHS [P30 DA 12121] NR 51 TC 45 Z9 45 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 5 PY 2007 VL 369 IS 1 BP 153 EP 167 DI 10.1016/j.virol.2007.07.017 PG 15 WC Virology SC Virology GA 232LW UT WOS:000251022200014 PM 17698160 ER PT J AU Feld, JJ Ghany, MG AF Feld, Jordan J. Ghany, Marc G. TI Evolution of therapy for chronic hepatitis B: Progressing from the simple to the complex SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID TERM FOLLOW-UP; ADEFOVIR DIPIVOXIL; INTERFERON-ALFA; LAMIVUDINE; MANAGEMENT; ENTECAVIR; DISEASE; TRIAL C1 NIDDKD, Natl Inst Hlth, Liver Dis Branch, Bethesda, MD 20892 USA. RP Ghany, MG (reprint author), NIDDKD, Natl Inst Hlth, Liver Dis Branch, Bldg 10, Rm 9B-16, 10 Ctr Dr, MSC 1800, Bethesda, MD 20892 USA. EM marcg@intra.niddk.nih.gov NR 20 TC 2 Z9 2 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 4 PY 2007 VL 147 IS 11 BP 806 EP U68 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 239SX UT WOS:000251539100010 PM 18056667 ER PT J AU Sauna, ZE Kim, IW Nandigama, K Kopp, S Chiba, P Ambudkar, SV AF Sauna, Zuben E. Kim, In-Wha Nandigama, Krishnamachary Kopp, Stephan Chiba, Peter Ambudkar, Suresh V. TI Catalytic cycle of ATP hydrolysis by P-glycoprotein: Evidence for formation of the E-S reaction intermediate with ATP-gamma-S, a nonhydrolyzable analogue of ATP SO BIOCHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING DOMAIN; ABC TRANSPORTER; TRANSITION-STATE; MULTIDRUG-RESISTANCE; FUNCTIONAL-CHARACTERIZATION; GLUTAMATE RESIDUES; CASSETTE DIMER; DRUG TRANSPORT; CONFORMATION; MECHANISM AB Structural and biochemical studies of ATP-binding cassette (ABC) transporters suggest that an ATP-driven dimerization of the nucleotide-binding domains (NBDs) is an important reaction intermediate of the transport cycle. Moreover, an asymmetric occlusion of ATP at one of the two ATP sites of P-glycoprotein (Pgp) may follow the formation of the symmetric dimer. It has also been postulated that ADP drives the dissociation of the dimer. In this study, we show that the E-S conformation of Pgp (previously demonstrated in the E556Q/E1201Q mutant Pgp) can be obtained with the wild-type protein by use of the nonhydrolyzable ATP analogue ATP-gamma-S. ATP-gamma-S is occluded into the Pgp NBDs at 34 degrees C but not at 4 degrees C,- whereas ATP is not occluded at either temperature. Using purified Pgp incorporated into proteoliposomes and ATP-gamma-S-35, we demonstrate that the occlusion of ATP-gamma-S-35 has an E-act of 60 kJ/mol and the stoichiometry of ATP-gamma-S-35:pgp is 1: 1 (mol/mol). Additionally, in the conserved Walker B mutant (E556Q/E1201Q) of Pgp, we find occlusion of the nucleoside triphosphate but not the nucleoside diphosphate. Furthermore, Pgp in the occluded nucleotide conformation has reduced affinity for transport substrates. These data provide evidence for the ATP-driven dimerization and ADP-driven dissociation of the NBDs, and although two ATP molecules may initiate dimerization, only one is driven to an occluded pre-hydrolysis intermediate state. Thus, in a full-length ABC transporter like Pgp, it is unlikely that there is complete association and disassociation of NBDs and the occluded nucleotide conformation at one of the NBDs provides the power-stroke at the transport-substrate site. C1 NIH, NCI, Ctr Canc Res, Cell Biol Lab, Bethesda, MD 20892 USA. Med Univ Vienna, Inst Med Chem, A-1090 Vienna, Austria. RP Ambudkar, SV (reprint author), NIH, NCI, Ctr Canc Res, Cell Biol Lab, Bldg 10, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov FU Intramural NIH HHS NR 54 TC 61 Z9 61 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 4 PY 2007 VL 46 IS 48 BP 13787 EP 13799 DI 10.1021/bi701385t PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 235NP UT WOS:000251241500012 PM 17988154 ER PT J AU Solomon, SD Lin, J Solomon, CG Jablonski, KA Rice, MM Steffes, M Domanski, M Hsia, J Gersh, BJ Arnold, JMO Rouleau, J Braunwald, E Pfeffer, MA AF Solomon, Scott D. Lin, Julie Solomon, Caren G. Jablonski, Kathleen A. Rice, Madeline Murguia Steffes, Michael Domanski, Michael Hsia, Judith Gersh, Bernard J. Arnold, J. Malcolm O. Rouleau, Jean Braunwald, Eugene Pfeffer, Marc A. CA PEACE Investigators TI Influence of albuminuria on cardiovascular risk in patients with stable coronary artery disease SO CIRCULATION LA English DT Article DE cardiovascular diseases; kidney; albuminuria ID CONVERTING-ENZYME-INHIBITION; MYOCARDIAL-INFARCTION; DIABETIC-NEPHROPATHY; ALBUMIN/CREATININE RATIO; KIDNEY-FUNCTION; PROTEINURIA; EVENTS; DEATH; MICROALBUMINURIA; OUTCOMES AB Background - Patients with chronic kidney disease are at increased risk for cardiovascular morbidity and mortality. We assessed the association between albuminuria and the risks for death and cardiovascular events among patients with stable coronary disease. Methods and Results - We studied patients enrolled in the Prevention of Events with an ACE inhibitor (PEACE) trial, in which patients with chronic stable coronary disease and preserved systolic function were randomized to trandolapril or placebo and followed up for a median of 4.8 years. The urinary albumin to creatinine ratio (ACR) assessed in a core laboratory in 2977 patients at baseline and in 1339 patients at follow-up (mean 34 months) was related to estimated glomerular filtration rate and outcomes. The majority of patients (73%) had a baseline ACR within the normal range (< 17 mu g/mg for men and < 25 mu g/mg for women). Independent of the estimated glomerular filtration rate and other baseline covariates, a higher ACR, even within the normal range, was associated with increased risks for all-cause mortality (P < 0.001) and cardiovascular death (P = 0.01). The effect of trandolapril therapy on outcomes was not modified significantly by the level of albuminuria. Nevertheless, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 versus 14.6 mu g/mg, P = 0.0002), after adjustment for baseline ACR, time between collections, and other covariates. An increase in ACR over time was associated with increased risk of cardiovascular death (hazard ratio per log ACR 1.74, 95% CI 1.08 to 2.82). Conclusions - Albuminuria, even in low levels within the normal range, is an independent predictor of cardiovascular and all-cause mortality. C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Renal Med, Boston, MA 02115 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. NHLBI, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Rochester, MN USA. London Hlth Sci Ctr, London, ON, Canada. Univ Montreal, Montreal, PQ, Canada. Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Solomon, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM ssolomon@rics.bwh.harvard.edu RI Solomon, Scott/I-5789-2013 FU NHLBI NIH HHS [N01 HC065149, N01HC65149] NR 20 TC 47 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 4 PY 2007 VL 116 IS 23 BP 2687 EP 2693 DI 10.1161/CIRCULATIONAHA.107.723270 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 237GE UT WOS:000251361400007 PM 18025537 ER PT J AU Hammer, JA Wu, XSF AF Hammer, John A. Wu, Xufeng S. TI Organelle motility: Running on unleadened SO CURRENT BIOLOGY LA English DT Editorial Material ID MYOSIN-VA; MELANOSOME TRANSPORT; LINKS RAB27A; MELANOPHILIN C1 NHLBI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Hammer, JA (reprint author), NHLBI, NIH, Cell Biol Lab, Bldg 50,Rm 2523, Bethesda, MD 20892 USA. EM hammerj@nhlbi.nih.gov NR 12 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 4 PY 2007 VL 17 IS 23 BP R1017 EP R1019 DI 10.1016/j.cub.2007.10.010 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 238XQ UT WOS:000251482100017 PM 18054764 ER PT J AU Schweers, RL Zhang, J Randall, MS Loyd, MR Li, W Dorsey, FC Kundu, M Opferman, JT Cleveland, JL Miller, JL Ney, PA AF Schweers, Rachel L. Zhang, Ji Randall, Mindy S. Loyd, Melanie R. Li, Weimin Dorsey, Frank C. Kundu, Mondira Opferman, Joseph T. Cleveland, John L. Miller, Jeffery L. Ney, Paul A. TI NIX is required for programmed mitochondrial clearance during reticulocyte maturation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autophagy; mitochondria; BCL2 family ID BCL-2 FAMILY-MEMBERS; CYTOCHROME-C; CELL-DEATH; ERYTHROID-DIFFERENTIATION; ORGANELLE DEGRADATION; PROTEIN; APOPTOSIS; AUTOPHAGY; BNIP3; BAX AB The regulated clearance of mitochondria is a well recognized but poorly understood aspect of cellular homeostasis, and defects in this process have been linked to aging, degenerative diseases, and cancer. Mitochondria are recycled through an autophagy-related process, and reticulocytes, which completely eliminate their mitochondria during maturation, provide a physiological model to study this phenomenon. Here, we show that mitochondrial clearance in reticulocytes requires the BCL2-related protein NIX (BNIP3L). Mitochondrial clearance does not require BAX, BAK, BCL-X-L, BIM, or PUMA, indicating that NIX does not function through established proapoptotic pathways. Similarly, NIX is not required for the induction of autophagy during terminal erythroid differentiation. NIX is required for the selective elimination of mitochondria, however, because mitochondrial clearance, in the absence of NIX, is arrested at the stage of mitochondrial incorporation into autophagosomes and autophagosome maturation. These results yield insight into the mechanism of mitochondrial clearance in higher eukaryotes. Furthermore, they show a BAX- and BAK-independent role for a BCL2-related protein in development. C1 St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA. Univ Tennessee, Hlth Sci Ctr, Integrated Program Biomed Sci, Memphis, TN 38126 USA. Scripps Res Inst Florida, Dept Canc Biol, Jupiter, FL 33458 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Natl Inst Hlth, NIDDK, Mol Med Branch, Bethesda, MD 20892 USA. RP Ney, PA (reprint author), St Jude Childrens Hosp, Dept Biochem, 332 N Lauderdale St, Memphis, TN 38105 USA. EM paul.ney@stjude.org FU NCI NIH HHS [R01 CA084214, R01 CA084214-06A1, R01 CA084214-07, R01 CA084214-08, R01 CA084214-09, R01 CA084214-10]; NIDDK NIH HHS [R21 DK074519-01, R21 DK074519, R21 DK074519-02] NR 44 TC 331 Z9 343 U1 5 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 4 PY 2007 VL 104 IS 49 BP 19500 EP 19505 DI 10.1073/pnas.0708818104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 239NU UT WOS:000251525800060 PM 18048346 ER PT J AU Hongpaisan, J Alkon, DL AF Hongpaisan, Jarin Alkon, Daniel L. TI A structural basis for enhancement of long-term associative memory in single dendritic spines regulated by PKC SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE learning and memory; synaptogenesis; Alzheimer's disease; mushroom spines; bryostatin ID PROTEIN-KINASE-C; SPATIAL MEMORY; HIPPOCAMPUS; CA1; NEURONS; POTENTIATION; EXPRESSION; MARCKS; CELLS; GENE AB Using both scanning confocal and electron microscopic morphometric measurements, we analyzed single dendritic spines of CA1 pyramidal cells in the hippocampi of water maze-trained rats vs. controls. Two days after completion of all training, we observed a memory-specific increase in the number of mushroom spines-all of which make synaptic contacts-but not in the numbers of filopodia or stubby or thin spines, as quantified with double-blind protocols in both scanning confocal and electron microscopic images. This memory-specific increase of mushroom spine number was enhanced by the PKC activator and candidate Alzheimer's disease therapeutic bryostatin, blocked by the PKC alpha-isozyme blocker Ro 31-8220, and accompanied by increases in the number of "perforated" postsynaptic densities, increased numbers of presynaptic vesicles, and the increased occurrence of double-synapse presynaptic boutons associated with the mushroom spines. These and other confocally imaged immunohistochemical results described here involving PKC substrates indicate that individual mushroom spines provide structural storage sites for long-term associative memory and sites for memory-specific synaptogenesis that involve PKC-regulated changes of spine shape, as well as PKC-regulated changes of pre- and postsynaptic ultrastructure. C1 Blanchette Rockeffeller Neurosci Inst, Morgantown, WV 26506 USA. Natl Inst Hlth, Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, Bethesda, MD 20892 USA. W Virginia Univ, Sch Med, Dept Neurol, Morgantown, WV 26506 USA. RP Alkon, DL (reprint author), Blanchette Rockeffeller Neurosci Inst, Morgantown, WV 26506 USA. EM dalkon@brni-jhu.org NR 24 TC 89 Z9 89 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 4 PY 2007 VL 104 IS 49 BP 19571 EP 19576 DI 10.1073/pnas.0709311104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 239NU UT WOS:000251525800072 PM 18073185 ER PT J AU Xie, T Chen, M Zhang, QH Ma, Z Weinstein, LS AF Xie, Tao Chen, Min Zhang, Qing-Hong Ma, Zheng Weinstein, Lee S. TI beta cell-specific deficiency of the stimulatory G protein alpha-subunit G(s)alpha leads to reduced beta cell mass and insulin-deficient diabetes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; PROTEIN-KINASE-B; GROWTH-FACTOR-I; IGF-I; SOMATOMEDIN-C; CYCLIN D2; ALPHA-S; PROLIFERATION; MICE; APOPTOSIS AB The G protein alpha-subunit G(s)alpha is required for hormone-stimulated cAMP generation. In pancreatic beta cells, G(s)alpha mediates the signaling of glucagon-like peptide 1 and other incretin hormones, which are implicated as important regulators of beta cell survival and insulin release. Studies have suggested that G(s)alpha/cAMP mediates these actions by stimulating insulin receptor substrate 2 (IRS2) expression. Mice with beta cell-specific G(s)alpha deficiency (beta GsKO) were generated by mating G(s)alpha-floxed mice to rat insulin II promoter-cre recombinase mice. beta GsKO mice had poor survival and postnatal growth with low serum insulin-like growth factor 1 levels. beta GsKO mice also developed severe hyperglycemia and glucose intolerance with severe hypoinsulinemia and reduced islet insulin content and glucose-stimulated insulin release. beta GsKO mice had markedly reduced average islet size and beta cell mass, which Was partially explained by reduced beta cell size. In addition, beta GsKO mice had significantly reduced beta cell proliferation and increased beta cell apoptosis and markedly reduced expression of the cell cycle protein cyclin D2. The effects on beta cell mass and proliferation, but not apoptosis, were present from birth. Unexpectedly expression of Irs2 and the downstream gene Pdx1 were unaffected. These results show that G(s)alpha/cAMP pathways are critical regulators of P cell function and proliferation that can work through IRS2-independent mechanisms. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov FU Intramural NIH HHS NR 36 TC 31 Z9 33 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 4 PY 2007 VL 104 IS 49 BP 19601 EP 19606 DI 10.1073/pnas.0704796104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 239NU UT WOS:000251525800077 PM 18029451 ER PT J AU Shaw, P Eckstrand, K Sharp, W Blumenthal, J Lerch, JP Greenstein, D Clasen, L Evans, A Giedd, J Rapoport, JL AF Shaw, P. Eckstrand, K. Sharp, W. Blumenthal, J. Lerch, J. P. Greenstein, D. Clasen, L. Evans, A. Giedd, J. Rapoport, J. L. TI Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cortical development; structural neuroimaging ID DEFICIT-HYPERACTIVITY DISORDER; CEREBRAL-CORTEX; GRAY-MATTER; DEVELOPMENTAL TRAJECTORIES; RESPONSE-INHIBITION; ANIMAL-MODELS; BRAIN GROWTH; MRI DATA; CHILDREN; ADOLESCENTS AB There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development. Using computational neuroanatomic techniques, we estimated cortical thickness at > 40,000 cerebral points from 824 magnetic resonance scans acquired prospectively on 223 children with ADHD and 223 typically developing controls. With this sample size, we could define the growth trajectory of each cortical point, delineating a phase of childhood increase followed by adolescent decrease in cortical thickness (a quadratic growth model). From these trajectories, the age of attaining peak cortical thickness was derived and used as an index of cortical maturation. We found maturation to progress in a similar manner regionally in both children with and without ADHD, with primary sensory areas attaining peak cortical thickness before polymodal, high-order association areas. However, there was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum: the median age by which 50% of the cortical points attained peak thickness for this group was 10.5 years (SE 0.01), which was significantly later than the median age of 7.5 years (SE 0.02) for typically developing controls (log rank test chi(1)(2) = 5,609, P < 1.0 x 10(-20)). The delay was most prominent in prefrontal regions important for control of cognitive processes including attention and motor planning. Neuroanatomic documentation of a delay in regional cortical maturation in ADHD has not been previously reported. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2T5, Canada. RP Shaw, P (reprint author), NIMH, Child Psychiat Branch, Room 3N202,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. EM shawp@mail.nih.gov RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU Intramural NIH HHS NR 62 TC 587 Z9 600 U1 22 U2 95 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 4 PY 2007 VL 104 IS 49 BP 19649 EP 19654 DI 10.1073/pnas.0707741104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 239NU UT WOS:000251525800085 PM 18024590 ER PT J AU Pettigrew, RI Peterson, KP Heetderks, W Seto, B AF Pettigrew, Roderic I. Peterson, Karen P. Heetderks, William Seto, Belinda TI The National Institute of Biomedical Imaging and Bioengineering marks its first five years SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 [Pettigrew, Roderic I.; Peterson, Karen P.; Heetderks, William; Seto, Belinda] NIH, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. RP Pettigrew, RI (reprint author), NIH, Natl Inst Biomed Imaging & Bioengn, 31 Ctr Dr,1C-14, Bethesda, MD 20892 USA. EM pettigrr@mail.nih.gov RI Peterson, Karen/E-8084-2015 OI Peterson, Karen/0000-0001-6737-8698 NR 0 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD DEC PY 2007 VL 14 IS 12 BP 1448 EP 1454 DI 10.1016/j.acra.2007.10.004 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 242TP UT WOS:000251749400004 PM 18172950 ER PT J AU Armato, SG Roberts, RY McNitt-Gray, MF Meyer, CR Reeves, AP McLennan, G Engelmann, RM Bland, PH Aberle, DR Kazerooni, EA MacMahon, H van Beek, EJR Yankelevitz, D Croft, BY Clarke, LP AF Armato, Samuel G., III Roberts, Rachael Y. McNitt-Gray, Michael F. Meyer, Charles R. Reeves, Anthony P. McLennan, Geoffrey Engelmann, Roger M. Bland, Peyton H. Aberle, Denise R. Kazerooni, Ella A. MacMahon, Heber van Beek, Edwin J. R. Yankelevitz, David Croft, Barbara Y. Clarke, Laurence P. TI The lung image database consortium (LIDC): Ensuring the integrity of expert-defined "truth" SO ACADEMIC RADIOLOGY LA English DT Article DE lung nodule; computed tomography (CT); thoracic imaging; database construction; computer-aided diagnosis (CAD); annotation; quality assurance (QA) ID COMPUTER-AIDED DIAGNOSIS; PULMONARY NODULES; PERFORMANCE; CT; RADIOLOGISTS; RESOURCE; SYSTEM AB Rationale and Objectives. Computer-aided diagnostic (CAD) systems fundamentally require the opinions of expert human observers to establish "truth" for algorithm development, training, and testing. The integrity of this "truth," however, must be established before investigators commit to this "gold standard" as the basis for their research. The purpose of this study was to develop a quality assurance (QA) model as an integral component of the "truth" collection process concerning the location and spatial extent of lung nodules observed on computed tomography (CT) scans to be included in the Lung Image Database Consortium (LIDC) public database. Materials and Methods. One hundred CT scans were interpreted by four radiologists through a two-phase process. For the first of these reads (the "blinded read phase"), radiologists independently identified and annotated lesions, assigning each to one of three categories: "nodule >= 3 mm," "nodule <3 mm," or "non-nodule >= 3 mm." For the second read (the "unblinded read phase"), the same radiologists independently evaluated the same CT scans, but with all of the annotations from the previously performed blinded reads presented; each radiologist could add to, edit, or delete their own marks; change the lesion category of their own marks; or leave their marks unchanged. The post-unblinded read set of marks was grouped into discrete nodules and subjected to the QA process, which consisted of identification of potential errors introduced during the complete image annotation process and correction of those errors. Seven categories of potential error were defined; any nodule with a mark that satisfied the criterion for one of these categories was referred to the radiologist who assigned that mark for either correction or confirmation that the mark was intentional. Results. A total of 105 QA issues were identified across 45 (45.0%) of the 100 CT scans. Radiologist review resulted in modifications to 101 (96.2%) of these potential errors. Twenty-one lesions erroneously marked as lung nodules after the unblinded reads had this designation removed through the QA process. Conclusions. The establishment of "truth" must incorporate a QA process to guarantee the integrity of the datasets that will provide the basis for the development, training, and testing of CAD systems. C1 [Armato, Samuel G., III; Roberts, Rachael Y.; Engelmann, Roger M.; MacMahon, Heber] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [McNitt-Gray, Michael F.; Aberle, Denise R.] Univ Calif Los Angeles, Dept Radiol Sci, Los Angeles, CA 90024 USA. [Meyer, Charles R.; Bland, Peyton H.; Kazerooni, Ella A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Reeves, Anthony P.] Cornell Univ, Dept Elect & Comp Engn, Ithaca, NY 14853 USA. [McLennan, Geoffrey; van Beek, Edwin J. R.] Univ Iowa, Dept Med, Dept Biomed Engn, Iowa City, IA USA. [Croft, Barbara Y.; Clarke, Laurence P.] NCI, Canc Imaging Program, Bethesda, MD 20892 USA. [Yankelevitz, David] Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. RP Armato, SG (reprint author), Univ Chicago, Dept Radiol, MC 2026,5841 S Maryland Ave, Chicago, IL 60637 USA. EM s-armato@uchicago.edu RI Croft, Barbara/D-1248-2013; OI Croft, Barbara/0000-0003-2544-150X; Aberle, Denise/0000-0002-8858-3401 FU NCI NIH HHS [U01 CA091090, U01 CA091085, U01 CA091090-01, U01 CA091090-02, U01 CA091090-03, U01 CA091090-04, U01 CA091090-05, U01 CA091090-05S1, U01 CA091099, U01 CA091100, U01 CA091103, U01CA091085, U01CA091090, U01CA091099, U01CA091100, U01CA091103] NR 14 TC 16 Z9 16 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD DEC PY 2007 VL 14 IS 12 BP 1455 EP 1463 DI 10.1016/j.acra.2007.08.006 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 242TP UT WOS:000251749400005 PM 18035275 ER PT J AU McNitt-Gray, MF Armato, SG Meyer, CR Reeves, AP McLennan, G Pais, RC Freymann, J Brown, MS Engelmann, RM Bland, PH Laderach, GE Piker, C Guo, J Towfic, Z Qing, DPY Yankelevitz, DF Aberle, DR van Beek, EJR MacMahon, H Kazerooni, EA Croft, BY Clarke, LP AF McNitt-Gray, Michael F. Armato, Samuel G., III Meyer, Charles R. Reeves, Anthony P. McLennan, Geoffrey Pais, Richie C. Freymann, John Brown, Matthew S. Engelmann, Roger M. Bland, Peyton H. Laderach, Gary E. Piker, Chris Guo, Junfeng Towfic, Zaid Qing, David P. -Y. Yankelevitz, David F. Aberle, Denise R. van Beek, Edwin J. R. MacMahon, Heber Kazerooni, Ella A. Croft, Barbara Y. Clarke, Laurence P. TI The Lung Image Database Consortium (LIDC) data collection process for nodule detection and annotation SO ACADEMIC RADIOLOGY LA English DT Article DE lung cancer; lung nodules; CT imaging; database; computer-aided diagnosis ID LOW-DOSE CT; INTRAOBSERVER VARIABILITY; VOLUMETRIC MEASUREMENTS; COMPUTED-TOMOGRAPHY; TUMOR MEASUREMENTS; CANCER; ENHANCEMENT; INTEROBSERVER; RADIOLOGISTS; RESOURCE AB Rationale and Objectives. The Lung linage Database Consortium (LIDC) is developing a publicly available database of thoracic computed tomography (CT) scans as a medical imaging research resource to promote the development of computer-aided detection or characterization of pulmonary nodules. To obtain the best estimate of the location and spatial extent of lung nodules, expert thoracic radiologists reviewed and annotated each scan. Because a consensus panel approach was neither feasible nor desirable, a unique two-phase, multicenter data collection process was developed to allow multiple radiologists at different centers to asynchronously review and annotate each CT scan. This data collection process was also intended to capture the variability among readers. Materials and Methods. Four radiologists reviewed each scan using the following process. In the first or "blinded" phase, each radiologist reviewed the CT scan independently. In the second or "unblinded" review phase, results from all four blinded reviews were compiled and presented to each radiologist for a second review, allowing the radiologists to review their own annotations together with the annotations of the other radiologists. The results of each radiologist's unblinded review were compiled to form the final unblinded review. An XML-based message system was developed to communicate the results of each reading. Results. This two-phase data collection process was designed, tested, and implemented across the LIDC. More than 500 CT scans have been read and annotated using this method by four expert readers; these scans either are currently publicly available at http://ncia.nci.nih.gov or will be in the near future. Conclusions. A unique data collection process was developed, tested, and implemented that allowed multiple readers at distributed sites to asynchronously review CT scans multiple times. This process captured the opinions of each reader regarding the location and spatial extent of lung nodules. C1 [McNitt-Gray, Michael F.; Pais, Richie C.; Brown, Matthew S.; Qing, David P. -Y.; Aberle, Denise R.] Univ Calif Los Angeles, David Geffenm Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Armato, Samuel G., III; Engelmann, Roger M.; MacMahon, Heber; Kazerooni, Ella A.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Meyer, Charles R.; Bland, Peyton H.; Laderach, Gary E.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Reeves, Anthony P.] Cornell Univ, Sch Elect Engn & Comp Sci, Ithaca, NY 14853 USA. [McLennan, Geoffrey; Freymann, John] Univ Iowa, Sch Med, Dept Internal Med, Iowa City, IA 52242 USA. [Freymann, John] SAIC Frederick Inc, Frederick, MD USA. [Piker, Chris; Guo, Junfeng; Towfic, Zaid; van Beek, Edwin J. R.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. [Yankelevitz, David F.] Cornell Univ, Weill Med Coll, Dept Radiol, Ithaca, NY 14853 USA. [Croft, Barbara Y.; Clarke, Laurence P.] NCI, Canc Imaging Program, Bethesda, MD 20892 USA. RP McNitt-Gray, MF (reprint author), Univ Calif Los Angeles, David Geffenm Sch Med, Dept Radiol, Suite 650,924 Westwood Blvd, Los Angeles, CA 90095 USA. EM mmcnittgray@mednet.ucfa.edu RI Croft, Barbara/D-1248-2013; OI Croft, Barbara/0000-0003-2544-150X; Aberle, Denise/0000-0002-8858-3401 FU NCI NIH HHS [U01 CA091090, U01 CA091085, U01 CA091099, U01 CA091103, U01 CA091103-05, U01CA091085, U01CA091090, U01CA091099, U01CA091100, U01CA091103] NR 23 TC 79 Z9 81 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD DEC PY 2007 VL 14 IS 12 BP 1464 EP 1474 DI 10.1016/j.acra.2007.07.021 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 242TP UT WOS:000251749400006 PM 18035276 ER PT J AU Reeves, AP Biancardi, AM Apanasovich, TV Meyer, CR MacMahon, H van Beek, EJR Kazerooni, EA Yankelevitz, D McNitt-Gray, MF McLennan, G Armato, SG Henschke, CI Aberle, DR Croft, BY Clarke, LP AF Reeves, Anthony P. Biancardi, Alberto M. Apanasovich, Tatiyana V. Meyer, Charles R. MacMahon, Heber van Beek, Edwin J. R. Kazerooni, Ella A. Yankelevitz, David McNitt-Gray, Michael F. McLennan, Geoffrey Armato, Samuel G., III Henschke, Claudia I. Aberle, Denise R. Croft, Barbara Y. Clarke, Laurence P. TI The Lung Image Database Consortium (LIDC): A comparison of different size metrics for pulmonary nodule measurements SO ACADEMIC RADIOLOGY LA English DT Article DE quantitative image analysis; X-ray CT; detection; lung nodule annotation; size metrics ID VOLUMETRIC MEASUREMENTS; COMPUTED-TOMOGRAPHY; TREATMENT RESPONSE; GROWTH-RATE; CT; METASTASES; CANCER; VARIABILITY; FILM AB Rationale and Objectives. The goal was to investigate the effects of choosing between different metrics in estimating the size of pulmonary nodules as a factor both of nodule characterization and of performance of computer aided detection systems, because the latter are always qualified with respect to a given size range of nodules. Materials and Methods. This study used 265 whole-lung CT scans documented by the Lung Image Database Consortium (LIDC) using their protocol for nodule evaluation. Each inspected lesion was reviewed independently by four experienced radiologists who provided boundary markings for nodules larger than 3 mm. Four size metrics, based on the boundary markings, were considered: a unidimensional and two bidimensional measures on a single image slice and a volumetric measurement based on all the image slices. The radiologist boundaries were processed and those with four markings were analyzed to characterize the interradiologist variation, while those with at least one marking were used to examine the difference between the metrics. Results. The processing of the annotations found 127 nodules marked by all of the four radiologists and an extended set of 518 nodules each having at least one observation with three-dimensional sizes ranging from 2.03 to 29.4 mm (average 7.05 mm, median 5.71 mm). A very high interobserver variation was observed for all these metrics: 95% of estimated standard deviations were in the following ranges for the three-dimensional, unidimensional, and two bidimensional size metrics, respectively (in mm): 0.49-1.25, 0.67-2.55, 0.78-2.11, and 0.96-2.69. Also, a very large difference among the metrics was observed: 0.95 probability-coverage region widths for the volume estimation conditional on unidimensional, and the two bidimensional size measurements of 10 mm were 7.32, 7.72, and 6.29 mm, respectively. Conclusions. The selection of data subsets for performance evaluation is highly impacted by the size metric choice. The LIDC plans to include a single size measure for each nodule in its database. This metric is not intended as a gold standard for nodule size; rather, it is intended to facilitate the selection of unique repeatable size limited nodule subsets. C1 [Reeves, Anthony P.; Biancardi, Alberto M.] Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY 14853 USA. [Apanasovich, Tatiyana V.] Cornell Univ, Ithaca, NY 14853 USA. [Meyer, Charles R.; Kazerooni, Ella A.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [MacMahon, Heber; Armato, Samuel G., III] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [van Beek, Edwin J. R.] Univ Iowa, Dept Radiol, Iowa City, IA USA. [Henschke, Claudia I.] Cornell Univ, Weill Med Coll, New York, NY USA. [McNitt-Gray, Michael F.; Aberle, Denise R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. [McLennan, Geoffrey] Univ Iowa, Iowa City, IA USA. [Croft, Barbara Y.; Clarke, Laurence P.] NCI, Canc Imaging Program, Bethesda, MD 20892 USA. RP Reeves, AP (reprint author), Cornell Univ, Sch Elect & Comp Engn, Rhodes Hall, Ithaca, NY 14853 USA. EM reeves@ece.cornell.edu RI Croft, Barbara/D-1248-2013; Apanasovich, Tatiyana/O-2376-2013; OI Croft, Barbara/0000-0003-2544-150X; Aberle, Denise/0000-0002-8858-3401 FU NCI NIH HHS [1U01 CA 091100, 1U01 CA 091085, 1U01 CA 091090, 1U01 CA 091099, 1U01 CA 091103, R01 CA078905, R21 CA101110-01A1, R33 CA101110, R33 CA101110-02, R33 CA101110-03, R33 CA101110-04, U01 CA091085, U01 CA091090, U01 CA091099, U01 CA091100, U01 CA091103] NR 26 TC 55 Z9 57 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD DEC PY 2007 VL 14 IS 12 BP 1475 EP 1485 DI 10.1016/j.acra.2007.09.005 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 242TP UT WOS:000251749400007 PM 18035277 ER PT J AU Timofeeva, OA Gaponenko, V Lockett, SJ Tarasov, SG Jiang, S Michejda, CJ Perantoni, AO Tarasova, NI AF Timofeeva, Olga A. Gaponenko, Vadim Lockett, Stephen J. Tarasov, Sergey G. Jiang, Sheng Michejda, Christopher J. Perantoni, Alan O. Tarasova, Nadya I. TI Rationally designed inhibitors identify STAT3 N-domain as a promising anticancer drug target SO ACS CHEMICAL BIOLOGY LA English DT Article ID ANTITUMOR-ACTIVITY; SIGNAL TRANSDUCER; GROWTH-FACTOR; IN-VIVO; ACTIVATION; PATHWAY; CANCER; INTERLEUKIN-6; APOPTOSIS; PEPTIDE AB Activation of the signal transducer and activator of transcription 3 (STAT3) is frequently detected in many cancer types. Activated STAT3 may participate in oncogenesis by stimulating cell proliferation and resisting apoptosis, as well as promoting tumor angiogenesis, invasion, and migration. Many STAT3-dependent cellular responses are mediated through interactions with other proteins, and the amino-terminal domain (N-domain) of STAT3 was proposed to be responsible for this. Our NMR studies revealed that synthetic analogs of the STAT4 second alpha-helix bind to the N-domain and perturb its structure. Structural data available for the STAT4 N-domain was used for the rational design of STAT3 helix 2 analogs with enhanced biological activity. Cell-permeable derivatives of the STAT3 second helix were found to directly and specifically bind to STAT3 but not STAT1 as determined by FRET analysis in cells expressing GFP-STAT3 and GFP-STAT1. Furthermore, they potently induced apoptotic death in breast cancer cells but not normal breast cells or STAT3-deficient fibroblasts. The inhibitors caused significant changes in the mitochondrial potential of cancer cells, leading to cell death. These compounds not only are promising drug candidates but also offer a convenient tool for studying the mechanisms of action of STAT transcription factors and have facilitated our understanding of the crucial role of the N-domain in STAT3 function. C1 [Jiang, Sheng; Michejda, Christopher J.; Tarasova, Nadya I.] NCI, Struct Biophys Lab, Mol Aspects Drug Design Sect, Frederick, MD 21702 USA. [Timofeeva, Olga A.; Perantoni, Alan O.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Timofeeva, Olga A.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. [Lockett, Stephen J.; Tarasov, Sergey G.] SAIC Inc, Image Anal Lab, Frederick, MD 21702 USA. [Tarasov, Sergey G.] NCI, Struct Biophys Lab, Frederick, MD 21702 USA. RP Tarasova, NI (reprint author), NCI, Struct Biophys Lab, Mol Aspects Drug Design Sect, Frederick, MD 21702 USA. EM tarasova@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 45 TC 41 Z9 45 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD DEC PY 2007 VL 2 IS 12 BP 799 EP 809 DI 10.1021/cb700186x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244ZX UT WOS:000251905100015 PM 18154267 ER PT J AU Wang, JW Dauter, M Alkire, R Joachimiak, A Dauter, Z AF Wang, Jiawei Dauter, Miroslawa Alkire, Randy Joachimiak, Andrzej Dauter, Zbigniew TI Triclinic lysozyme at 0.65 angstrom resolution SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID EGG-WHITE LYSOZYME; X-RAY-DIFFRACTION; ULTRA-HIGH-RESOLUTION; ATOMIC-RESOLUTION; CRYSTAL-STRUCTURE; PROTEIN DENATURATION; NEUTRON-DIFFRACTION; ELECTRON-DENSITY; LEAST-SQUARES; REFINEMENT AB The crystal structure of triclinic hen egg-white lysozyme (HEWL) has been refined against diffraction data extending to 0.65 angstrom resolution measured at 100 K using synchrotron radiation. Refinement with anisotropic displacement parameters and with the removal of stereochemical restraints for the well ordered parts of the structure converged with a conventional R factor of 8.39% and an R-free of 9.52%. The use of full-matrix refinement provided an estimate of the variances in the derived parameters. In addition to the 129-residue protein, a total of 170 water molecules, nine nitrate ions, one acetate ion and three ethylene glycol molecules were located in the electron-density map. Eight sections of the main chain and many side chains were modeled with alternate conformations. The occupancies of the water sites were refined and this step is meaningful when assessed by use of the free R factor. A detailed description and comparison of the structure are made with reference to the previously reported triclinic HEWL structures refined at 0.925 angstrom (at the low temperature of 120 K) and at 0.95 angstrom resolution (at room temperature). C1 Argonne Natl Lab, Biosci Div, Struct Biol Ctr, Argonne, IL 60439 USA. Argonne Natl Lab, Basic Res Program, SAIC Frederick Inc, Argonne, IL 60439 USA. Argonne Natl Lab, Natl Canc Inst, MCL, Synchrotron Radiat Res Sect, Argonne, IL 60439 USA. RP Joachimiak, A (reprint author), Argonne Natl Lab, Biosci Div, Struct Biol Ctr, Argonne, IL 60439 USA. EM andrzejj@anl.gov; dauter@anl.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 58 TC 78 Z9 78 U1 1 U2 14 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD DEC PY 2007 VL 63 BP 1254 EP 1268 DI 10.1107/S0907444907054224 PN 12 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 232OV UT WOS:000251029900007 PM 18084073 ER PT J AU Jaskolski, M Gilski, M Dauter, Z Wlodawer, A AF Jaskolski, Mariusz Gilski, Miroslaw Dauter, Zbigniew Wlodawer, Alexander TI Numerology versus reality: a voice in a recent dispute SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Letter ID REFINEMENT TARGETS; PROTEIN STRUCTURES; ACCURATE; DEVIATE C1 NCI, Macromol Crystallog Lab, Prot Struct Sect, Frederick, MD 21702 USA. Adam Mickiewicz Univ Poznan, Fac Chem, Dept Crystallog, Poznan, Poland. Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, Poznan, Poland. Argonne Natl Lab, NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA. RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Prot Struct Sect, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov NR 12 TC 8 Z9 8 U1 0 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD DEC PY 2007 VL 63 BP 1282 EP 1283 DI 10.1107/S0907444907049359 PN 12 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 232OV UT WOS:000251029900010 PM 18084076 ER PT J AU Panlilio, LV Goldberg, SR AF Panlilio, Leigh V. Goldberg, Steven R. TI Self-administration of drugs in animals and humans as a model and an investigative tool SO ADDICTION LA English DT Article DE abuse liability; addiction; animal models; escalation; operant behavior; reinforcement; self-administration; translational research ID 2ND-ORDER SCHEDULES; SEEKING BEHAVIOR; COCAINE-SEEKING; RHESUS-MONKEYS; D-AMPHETAMINE; RATS; REINFORCEMENT; DEPENDENCE; REINSTATEMENT; MORPHINE AB Aims To review briefly the methods, assumptions, models, accomplishments, drawbacks and future directions of research using drug self-administration in animals and humans. Background The use of drug self-administration to study addiction is based on the assumption that drugs reinforce the behavior that results in their delivery. A wide range of drug self-administration techniques have been developed to model specific aspects of addiction. These techniques are highly amenable to being combined with a wide variety of neuroscience techniques. Conclusions The identification of drug use as behavior that is reinforced by drugs has contributed greatly to the understanding and treatment of addiction. As part of a program of pre-clinical research that also involves screening with a variety of simpler behavioral techniques, drug self-administration procedures can provide an important last step in testing potential treatments for addiction. There is currently a concerted effort to develop self-administration procedures that model the extreme nature of the behavior engendered by addiction. As advances continue to be made in neuroscience techniques, self-administration should continue to provide a means of applying these techniques within a sophisticated and valid model of human drug addiction. C1 Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH DHHS, Baltimore, MD 21224 USA. RP Goldberg, SR (reprint author), Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH DHHS, 5500 Nathan Shoch Dr, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999, Z01 DA000001-23] NR 41 TC 70 Z9 70 U1 4 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 2007 VL 102 IS 12 BP 1863 EP 1870 DI 10.1111/j.1360-0443.2007.02011.x PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 234ST UT WOS:000251185000003 PM 18031422 ER PT J AU Vocci, FJ AF Vocci, Frank J. TI Can replacement therapy work in the treatment of cocaine dependence? And what are we replacing anyway? SO ADDICTION LA English DT Editorial Material C1 Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. RP Vocci, FJ (reprint author), Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. EM fvocci@nida.nih.gov NR 11 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 2007 VL 102 IS 12 BP 1888 EP 1889 DI 10.1111/j.1360-0443.2007.02014.x PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 234ST UT WOS:000251185000005 PM 18031424 ER PT J AU Leventhal, AM Waters, AJ Boyd, S Moolchan, ET Helshman, SJ Lerman, C Pickworth, WB AF Leventhal, Adam M. Waters, Andrew J. Boyd, Susan Moolchan, Eric T. Helshman, Stephen J. Lerman, Caryn Pickworth, Wallace B. TI Associations between Cloninger's temperament dimensions and acute tobacco withdrawal SO ADDICTIVE BEHAVIORS LA English DT Article DE temperament; temperament and character inventory; nicotine withdrawal; novelty seeking; harm avoidance; reward dependence ID RECEPTOR GENE POLYMORPHISM; HUMAN PERSONALITY-TRAIT; EXON-III POLYMORPHISM; NOVELTY SEEKING; CHARACTER INVENTORY; NICOTINE DEPENDENCE; REWARD-DEPENDENCE; SMOKING-BEHAVIOR; NEGATIVE-AFFECT; MEDIATING ROLE AB This study examined associations between three temperament dimensions measured by the Temperament and Character Inventory-125 [Cloninger, C.R. (1992). The Temperament and Character Inventory-125 (TCI-125; Version 1.)] and tobacco abstinence effects. Smokers (N=203, >= 15 cigarettes/day) attended two laboratory sessions, one following 12 It of abstinence and the other following ad libitum smoking (order counterbalanced). Participants completed measures of withdrawal symptoms, cigarette urges, and affect. Smokers high in Novelty Seeking reported greater abstinence-induced increases in several nicotine withdrawal symptoms, negative affect, and cigarette craving. Smokers high in Harm Avoidance reported greater abstinence- induced increases in negative affect and urges to smoke to relieve distress. Reward Dependence was not associated with abstinence effects. Novelty Seeking and Harm Avoidance showed independent predictive associations with negative affect and urges, and their associations with abstinence effects persisted when controlling for FTND scores. Smokers with different temperaments display different patterns of acute tobacco withdrawal, and may benefit from treatments matched to their particular abstinence profile. (C) 2007 Elsevier Ltd. All rights reserved. C1 Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX USA. Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. Univ Penn, Philadelphia, PA 19104 USA. RP Leventhal, AM (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Box G-S121, Providence, RI 02912 USA. EM adam_Ieventhal@brown.edu FU NCI NIH HHS [P50 CA084718, P50 CA084718-01]; PHS HHS [P5084718] NR 53 TC 26 Z9 28 U1 3 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD DEC PY 2007 VL 32 IS 12 BP 2976 EP 2989 DI 10.1016/j.addbeh.2007.06.014 PG 14 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 231XJ UT WOS:000250982200022 PM 17624682 ER PT J AU Waters, AJ Heishman, SJ Lerman, C Pickworth, W AF Waters, Andrew J. Heishman, Stephen J. Lerman, Caryn Pickworth, Wallace TI Enhanced identification of smoking-related words during the attentional blink in smokers SO ADDICTIVE BEHAVIORS LA English DT Article DE attentional blink; attentional bias; smoking cues AB The attentional blink (AB) occurs when ongoing processing of one target (T1) in a series of rapidly presented stimuli impairs processing of a subsequently presented second target (T2), such that T2 cannot be consciously perceived or reported. There is evidence that the AB can be influenced by the emotional or motivational salience of T2. We examined whether the AB could be attenuated by smoking-related stimuli in smokers. Heavy smokers (N=55) performed an AB task on two occasions, once following 12-h of abstinence and once following ad libitum smoking. Us were either smoking-related or neutral (household-related) words, and lagged T1 by 0 to 7 distracter words. T1s were all neutral words. Each word was presented for 130 ms. Subjects were required to recall T1 and T2 immediately after each trial. There was a significant word type by lag interaction, whereby smoking-related T2s were recalled better than neutral T2s at early, but not late, lags. The word type effect at early lags was significantly associated with attentional bias assessed on the smoking Stroop task, but was not significantly moderated by abstinence. These data indicate that, in heavy smokers, smoking-related stimuli are more likely to engage conscious awareness than neutral words under conditions of limited attentional resources. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Texas Houston, MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Waters, AJ (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Behav Sci, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM ajwaters@mdanderson.org FU NCI NIH HHS [P50 CA084718-01, P50 CA084718]; PHS HHS [P5084718] NR 9 TC 11 Z9 12 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD DEC PY 2007 VL 32 IS 12 BP 3077 EP 3082 DI 10.1016/j.addbeh.2007.05.016 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 231XJ UT WOS:000250982200033 PM 17616446 ER PT J AU Robinson, HL Sharma, S Zhao, J Kannanganat, S Lai, LL Chennareddi, L Yu, TW Montefiori, DC Amara, RR Wyatt, LS Moss, B AF Robinson, Harriet L. Sharma, Sunita Zhao, Jun Kannanganat, Sunil Lai, Lilin Chennareddi, Lakshmi Yu, Tianwei Montefiori, David C. Amara, Rama Rao Wyatt, Linda S. Moss, Bernard TI Immunogenicity in Macaques of the clinical product for a clade B DNA/MVA HIV vaccine: Elicitation of IFN-gamma, IL-2, and TNF-alpha coproducing CD4 and CD8 T cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS; MVA VACCINES; DNA; RESPONSES; EXPRESSION; CHALLENGE; TYPE-1 AB The clinical product for a clade B HIV DNA/MVA vaccine expressing Gag, Pol, and Env has been tested for immunogenicity in macaques. Responding T cells were at the threshold for detection following DNA priming at weeks 0 and 8 but underwent sharp expansions and contractions following MVA boosting at weeks 16 and 24. Both CD4 and CD8 T cell responses had high frequencies of cytokine coproducing cells with > 50% of the memory cells coproducing multiple cytokines including IL-2. The highest responses were elicited to Gag, followed by Env and then Pol. In two of six macaques, the vaccine also elicited low levels of neutralizing Ab for easy to neutralize clade B isolates. C1 [Robinson, Harriet L.; Sharma, Sunita; Zhao, Jun; Kannanganat, Sunil; Lai, Lilin; Chennareddi, Lakshmi; Amara, Rama Rao] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [Robinson, Harriet L.; Sharma, Sunita; Zhao, Jun; Kannanganat, Sunil; Lai, Lilin; Chennareddi, Lakshmi; Yu, Tianwei; Amara, Rama Rao] Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Yu, Tianwei] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Wyatt, Linda S.; Moss, Bernard] NIAID, Natl Inst Hlth, Viral Dis Lab, Bethesda, MD 20892 USA. RP Robinson, HL (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd, Atlanta, GA 30329 USA. EM hrobins@rmy.emory.edu FU NCRR NIH HHS [P51 RR00165]; NIAID NIH HHS [AI30034, P01 AI 49364]; NIDA NIH HHS [P30 DA 12121] NR 14 TC 24 Z9 24 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 2007 VL 23 IS 12 BP 1555 EP 1561 DI 10.1089/aid.2007.0165 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 246PL UT WOS:000252019200013 PM 18160013 ER PT J AU Dawson, DA Goldstein, RB Grant, BF AF Dawson, Deborah A. Goldstein, Rise B. Grant, Bridget F. TI Rates and correlates of relapse among individuals in remission from DSM-IV alcohol dependence: A 3-year follow-up SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol dependence; remission; relapse ID SUBSTANCE USE DISORDERS; GENERAL-POPULATION; UNITED-STATES; DRUG-USE; NICOTINE DEPENDENCE; DRINKING OUTCOMES; PROJECT MATCH; AUDADIS-ADR; TERM COURSE; RECOVERY AB Background: There is little information on the stability of abstinent and nonabstinent remission from alcohol dependence in the general U.S. population. The aim of this study was to examine longitudinal changes in recovery status among individuals in remission from DSM-IV alcohol dependence, including rates and correlates of relapse, over a 3-year period. Methods: This analysis is based on data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample of U.S. adults aged 18 years and older originally interviewed in 2001 to 2002 and reinterviewed in 2004 to 2005. The Wave 1 NESARC identified 2,109 individuals who met the DSM-IV criteria for full remission from alcohol dependence. Of these, 1,772 were reinterviewed at Wave 2, comprising the analytic sample for this study. Recovery status at Wave 2 was examined as a function of type of remission at Wave 1, with a focus on rates of relapse, alternately defined as recurrence of any alcohol use disorder (AUD) symptoms and recurrence of DSM-IV alcohol dependence. Logistic regression models were used to estimate the odds of relapse among asymptomatic risk drinkers and low-risk drinkers relative to abstainers, adjusted for a wide range of potential confounders. Results: By Wave 2, 51.0% of the Wave 1 asymptomatic risk drinkers had experienced the recurrence of AUD symptoms, compared with 27.2% of low-risk drinkers and 7.3% of abstainers. Across all ages combined, the adjusted odds of recurrence of AUD symptoms relative to abstainers were 14.6 times as great for asymptomatic risk drinkers and 5.8 times as great for low-risk drinkers. The proportions of individuals who had experienced the recurrence of dependence were 10.2, 4.0, and 2.9%, respectively, and the adjusted odds ratios relative to abstainers were 7.0 for asymptomatic risk drinkers and 3.0 for low-risk drinkers. Age significantly modified the association between type of remission and relapse. Differences by type of remission were not significant for younger alcoholics, who had the highest rates of relapse. Conclusion: Abstinence represents the most stable form of remission for most recovering alcoholics. Study findings highlight the need for better approaches to maintaining recovery among young adults in remission from alcohol dependence, who are at particularly high risk of relapse. C1 NIAAA, NIH, LEB, Div Clin & Biol Res, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, NIH, LEB, Div Clin & Biol Res, Room 3071,5635 Fishers Lane,MSC9304, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 NR 42 TC 109 Z9 111 U1 4 U2 20 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2007 VL 31 IS 12 BP 2036 EP 2045 DI 10.1111/j.1530-0277.2007.00536.x PG 10 WC Substance Abuse SC Substance Abuse GA 234SR UT WOS:000251184800010 PM 18034696 ER PT J AU Fox, ER Wilson, RS Penman, AD King, JJ Towery, JG Butler, KR McMullan, MR Skelton, TN Mosley, TH Taylor, HA AF Fox, Ervin R. Wilson, Richard S. Penman, Alan D. King, John J. Towery, James G. Butler, Kenneth R. McMullan, Michael R. Skelton, Thomas N. Mosley, Thomas H. Taylor, Herman A. TI Epidemiology of pure valvular regurgitation in the large middle-aged African American cohort of the Atherosclerosis Risk in Communities study SO AMERICAN HEART JOURNAL LA English DT Article ID LEFT-VENTRICULAR MASS; HEART-DISEASE; MITRAL REGURGITATION; PREVALENCE; HYPERTROPHY; COMMITTEE; OBESITY; UPDATE AB Background There are limited data on the prevalence and the clinical and. echocardiographic correlates of pure valvular regurgitation in African Americans despite the higher rates of cardiovascular disease in this group. Purpose The Jackson, Mississippi, site of the Atherosclerosis Risk in Communities study provides a unique opportunity to study mitral regurgitation (MR), tricuspid regurgitation (TR), and aortic regurgitation (AR) in this population. Methods There were 2285 participants who were available for analysis. The prevalence rates of MR, TR,and AR by severity were calculated for participants aged 50 to 59, 60 to 69, and >= 70 years. Multivariable regression analyses were conducted to determine clinical and echo variables associated with the presence of MR, TR, and AR. Results Mild or greater MR and TR were present in 14.7% and 17.2% of participants, respectively. Aortic regurgitation was present in 15.6% of participants. In the multivariable regression model, MR was independently associated with age, sex, lower body mass index (BMI), systolic blood pressure, left atrial size, left ventricular (LV) diastolic diameter, and low LV ejection fraction. Tricuspid regurgitation was independently associated with age, sex, lower BMI, high-density lipid, left atrial size, and lower relative wall thickness. Aortic regurgitation was independently associated with age, sex, lower BMI, systolic blood pressure, LV diastolic diameter, LV hypertrophy, and low LV ejection fraction. Conclusion In this middle-aged African Americans cohort, the prevalence of mild to greater MR and TR was similar to that seen in other cohorts; however, AR was more prevalent. Several cardiovascular risk factors and echo parameters were identified as independent correlates of valvular regurgitation. C1 Univ Mississippi, Med Ctr, University, MS 38677 USA. NHLBI, Jackson Heart Study, Jackson, MS USA. RP Fox, ER (reprint author), Med Univ Mississippi, Med Ctr, Jackson Heart Study, Examinat Ctr, 2500 N State St, Jackson, MS 39216 USA. EM efox@medicine.umsmed.edu FU NHLBI NIH HHS [N01-HC-55020, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55021, N01-HC-55022, N01-HC-95170, N01-HC-95171, N01-HC-95172] NR 22 TC 14 Z9 15 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2007 VL 154 IS 6 BP 1229 EP 1234 DI 10.1016/j.ahj.2007.07.030 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 237SH UT WOS:000251396200033 PM 18035099 ER PT J AU Berglund, L Lefevre, M Ginsberg, HN Kris-Etherton, PM Elmer, PJ Stewart, PW Ershow, A Pearson, TA Dennis, BH Roheim, PS Ramakrishnan, R Reed, R Stewart, K Phillips, KM AF Berglund, Lars Lefevre, Michael Ginsberg, Henry N. Kris-Etherton, Penny M. Elmer, Patricia J. Stewart, Paul W. Ershow, Abby Pearson, Thomas A. Dennis, Barbara H. Roheim, Paul S. Ramakrishnan, Rajasekhar Reed, Roberta Stewart, Kent Phillips, Katherine M. CA DELTA Investigators TI Comparison of monounsaturated fat with carbohydrates as a replacement for saturated fat in subjects with a high metabolic risk profile: studies in the fasting and postprandial states SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE diet; nutrition; fatty acids; lipids; lipoproteins ID AMERICAN-HEART-ASSOCIATION; DEPENDENT DIABETES-MELLITUS; CHOLESTEROL-LOWERING DIET; LOW-DENSITY-LIPOPROTEIN; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; PLASMA-CHOLESTEROL; SERUM-LIPIDS; HEALTHY-MEN; MODERATE HYPERCHOLESTEROLEMIA AB Background: In subjects with a high prevalence of metabolic risk abnormalities, the preferred replacement for saturated fat is unresolved. Objective: The objective was to study whether carbohydrate or monounsaturated fat is a preferred replacement for saturated fat. Design: Fifty-two men and 33 women, selected to have any combination of HDL cholesterol <= 30th percentile, triacylglycerol 70th percentile, or insulin >= 70th percentile, were enrolled in a 3-period, 7-wk randomized crossover study. The subjects consumed an average American diet (AAD; 36% of energy from fat) and 2 additional diets in which 7% of energy from saturated fat was replaced with either carbohydrate (CHO diet) or monounsaturated fatty acids (MUFA diet). Results: Relative to the AAD, LDL cholesterol was lower with both the CHO (-7.0%) and MUFA (-6.3%) diets, whereas the difference in HDL cholesterol was smaller during the MUFA diet (-4.3%) than during the CHO diet (-7.2%). Plasma triacylglycerols tended to be lower with the MUFA diet, but were significantly higher with the CHO diet. Although dietary lipid responses varied on the basis of baseline lipid profiles, the response to diet did not differ between subjects with or without the metabolic syndrome or with or without insulin resistance. Postprandial triacylglycerol concentrations did not differ significantly between the diets. Lipoprotein(a) concentrations increased with both the CHO (20%) and MUFA (11%) diets relative to the AAD. Conclusions: In the study population, who were at increased risk of coronary artery disease, MUFA provided a greater reduction in risk as a replacement for saturated fat than did carbohydrate. C1 [Berglund, Lars; Ginsberg, Henry N.; Ramakrishnan, Rajasekhar] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Lefevre, Michael] Pennington Biomed Res Ctr, Div Nutr & Chron Dis, Baton Rouge, LA USA. [Kris-Etherton, Penny M.] Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. [Elmer, Patricia J.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN USA. [Stewart, Paul W.] Univ N Carolina, Collaborat Studies Coordinating Ctr, Dept Biostat, Chapel Hill, NC USA. [Dennis, Barbara H.] Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC USA. [Dennis, Barbara H.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Ershow, Abby] NHLBI, NIH, Div Cardiovasc Dis, Bethesda, MD 20892 USA. [Pearson, Thomas A.; Reed, Roberta] Mary Imogene Bassett Hosp, Res Inst, Cooperstown, NY 13326 USA. [Roheim, Paul S.] Louisiana State Univ, Sch Med, Dept Physiol, New Orleans, LA USA. [Stewart, Kent; Phillips, Katherine M.] Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA. RP Berglund, L (reprint author), Univ Calif Davis, Med Ctr, Dept Med, CRISP, 2921 Stockton Boulevard,Suite 1400, Sacramento, CA 95817 USA. EM lars.berglund@ucdmc.ucdavis.edu RI Lefevre, Michael/B-5030-2014; OI Lefevre, Michael/0000-0002-2046-3593; Phillips, Katherine/0000-0002-4586-8538 FU NCRR NIH HHS [M01 RR00645]; NHLBI NIH HHS [5 U01 HL049644, HL049648, HL049649, HL049651, HL049659] NR 59 TC 64 Z9 66 U1 0 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 2007 VL 86 IS 6 BP 1611 EP 1620 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 240GN UT WOS:000251575500007 PM 18065577 ER PT J AU Kan, H Stevens, J Heiss, G Klein, R Rose, KM London, SJ AF Kan, Haidong Stevens, June Heiss, Gerardo Klein, Ronald Rose, Kathryn M. London, Stephanie J. TI Dietary fiber intake and retinal vascular caliber in the Atherosclerosis Risk in Communities Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dietary fiber; cardiovascular diseases; microcirculation; retinal abnormalities; cereal ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; GLYCEMIC INDEX; MICROVASCULAR ABNORMALITIES; NUTRITIONAL FACTORS; DIABETES-MELLITUS; VESSEL DIAMETERS; ARTERY-DISEASE AB Background: Dietary fiber appears to decrease the risk of cardiovascular morbidity and mortality. Microvascular abnormalities can be observed by retinal examination and contribute to the pathogenesis of various cardiovascular diseases. The impact of dietary fiber on the retinal microvasculature is not known. Objective: We aimed to examine the association between dietary fiber intake and retinal vascular caliber. Design: At the third visit (1993-1995) of the Atherosclerosis Risk in Communities (ARIC) Study, a population-based cohort of adults in 4 US communities, the retinal vascular caliber of 10 659 participants was measured and summarized from digital retinal photographs. Usual dietary intake during the same period was assessed with a 66-item food-frequency questionnaire. Results: After control for potential confounders including hypertension, diabetes, lipids, demographic factors, cigarette smoking, total energy intake, micronutrients intake, and other cardiovascular disease risk factors, higher intake of fiber from all sources and from cereal were significantly associated with wider retinal arteriolar caliber and narrower venular caliber. Participants in the highest quintile of fiber intake from all sources had a 1.05-mu m larger arteriolar caliber (P for trend = 0.012) and a 1.11-mu m smaller venular caliber (P for trend = 0.029). Conclusions: Dietary fiber was related to wider retinal arteriolar caliber and narrower venular caliber, which are associated with a lower risk of cardiovascular disease. These data add to the growing evidence of the benefits of fiber intake on various aspects of cardiovascular pathogenesis. C1 [Kan, Haidong; London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Stevens, June] Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. [Stevens, June; Heiss, Gerardo; Rose, Kathryn M.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Klein, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. RP Kan, H (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS [Z01 ES043012-09]; NHLBI NIH HHS [N01 HC55015, N01 HC55016, N01 HC55018, N01 HC55019, N01 HC55020, N01 HC55021, N01 HC55022, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022]; NIEHS NIH HHS [Z01 ES043012] NR 50 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 2007 VL 86 IS 6 BP 1626 EP 1632 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 240GN UT WOS:000251575500009 PM 18065579 ER PT J AU Newby, PK Maras, J Bakun, P Muller, D Ferrucci, L Tucker, KL AF Newby, P. K. Maras, Janice Bakun, Peter Muller, Denis Ferrucci, Luigi Tucker, Katherine L. TI Intake of whole grains, refined grains, and cereal fiber measured with 7-d diet records and associations with risk factors for chronic disease SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE whole grains; refined grains; fiber; diet records; risk factors ID DENSITY-LIPOPROTEIN CHOLESTEROL; DIANA RANDOMIZED-TRIAL; CORONARY-HEART-DISEASE; INSULIN SENSITIVITY; METABOLIC SYNDROME; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; WAIST CIRCUMFERENCE; GLUCOSE-TOLERANCE; WEIGHT-GAIN AB Background: Research studies examining foods are important, because they account for biological interactions that might otherwise be lost in the analysis of individual nutrients. Single-nutrient studies are also needed to explore the mechanisms by which foods may be protective. Objective: Our objective was to examine associations between whole grains, refined grains, and cereal fiber and chronic disease risk factors. Design: In a cross-sectional analysis of participants in the Baltimore Longitudinal Study of Aging, associations between dietary intakes and risk factors were examined with multivariate linear regression analysis. Dietary intakes were assessed with 7-d dietary records and quantified in g/d. Results: Compared with subjects in the lowest quintile (Q1) of whole-grain intake, subjects in the highest quintile (Q5) had lower body mass index (BMI; in kg/m(2); Q 1: 25.5; Q5: 24.8; P for trend < 0.0001) and weight(Q1: 75.0kg; Q5:72.4 kg; Pfortrend = 0.004) and smaller waist circumference Q 1: 87.4 cm; Q5: 85.0 cm; P for trend = 0.002). Whole grains were also inversely associated with total cholesterol (P for trend = 0.02), LDL cholesterol (P for trend = 0.04), and 2-h glucose (P for trend = 0.0006). Associations between cereal fiber and anthropometrics and plasma lipids were similar. In subgroup analyses, refined grains were positively associated with fasting insulin among women (P for trend = 0.002). Conclusions: Similar associations of whole grains and cereal fiber with weight, BMI, waist circumference, plasma cholesterol, and 2-h glucose were observed, suggesting that cereal fiber and its constituents may in part mediate these relations. Refined grains were associated with fasting insulin among women but not men. Additional research should explore potential interaction effects with BMI, sex, age, and genes. C1 [Newby, P. K.] Boston Univ, Med Ctr, Sch Med, Dept Pediat, Boston, MA 02118 USA. [Maras, Janice; Bakun, Peter; Tucker, Katherine L.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Muller, Denis; Ferrucci, Luigi] NIH, Natl Inst Aging, Baltimore, MD USA. RP Newby, PK (reprint author), Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. EM pk.newby@bmc.org RI Tucker, Katherine/A-4545-2010; OI Tucker, Katherine/0000-0001-7640-662X FU Intramural NIH HHS [Z01 AG000015-49] NR 60 TC 90 Z9 93 U1 2 U2 14 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 2007 VL 86 IS 6 BP 1745 EP 1753 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 240GN UT WOS:000251575500025 PM 18065595 ER PT J AU Millen, AE Subar, AF Graubard, BI Peters, U Hayes, RB Weissfeld, JL Yokochi, LA Zieglerfor, RG AF Millen, Amy E. Subar, Amy F. Graubard, Barry I. Peters, Ulrike Hayes, Richard B. Weissfeld, Joel L. Yokochi, Lance A. Zieglerfor, Regina G. TI Fruit and vegetable intake and prevalence of colorectal adenoma in a cancer screening trial(1-3) SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE fruit; vegetables; epidemiology; colorectal neoplasms; adenoma; diet ID FOOD FREQUENCY QUESTIONNAIRES; DIET HISTORY QUESTIONNAIRE; COLON-CANCER; RISK-FACTORS; CARCINOMA SEQUENCE; GLUCOSE CONTROL; FAMILY-HISTORY; WOMENS HEALTH; FOLATE INTAKE; LARGE BOWEL AB Background: Research on the association between fruit and vegetable intake and risk of colorectal adenoma is inconclusive. Objective: We studied whether intake of fruit, vegetables, or their subgroups is associated with a lower risk of prevalent colorectal adenoma. Design: In men and women (aged 55-74 y) who were screened for colorectal cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (1993-2001), we compared 3057 cases with at least one prevalent histologically verified adenoma of the distal large bowel with 29 413 control subjects. Using a food-frequency questionnaire, we quantified intake of fruit and vegetables in the 12 mo before screening as energy-adjusted pyramid servings/d (ps/d). Adjusted odds ratios (ORs) and 95% Cls were estimated by logistic regression. Results: Risk of distal adenoma was significantly lower among subjects in high (approximate to 5.7 ps/d) versus low (approximate to 1.2 ps/d) quintiles of total fruit intake (OR: 0.75; 95% CI: 0.66, 0.86, P for trend <0.001), which was not completely explained by dietary folate or fiber intake. Inverse associations between adenoma and total fruit intake were observed regardless of adenoma histopathology and multiplicity. However, the protective effect was seen only for colon and not rectal adenoma. Total vegetable intake was not significantly associated with reduced risk of adenoma. ORs for colorectal adenoma among persons with high versus low intakes of deep-yellow vegetables, dark-green vegetables, and onions and garlic were significantly related to lower risk of adenoma, although the P for trend for dark-green vegetables was not significant. Conclusion: Diets rich in fruit and deep-yellow vegetables, darkgreen vegetables, and onions and garlic are modestly associated with reduced risk of colorectal adenoma, a precursor of colorectal cancer. C1 [Millen, Amy E.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Buffalo, NY 14214 USA. [Subar, Amy F.] Natl Canc Ctr, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, Bethesda, MD USA. [Graubard, Barry I.] Natl Canc Inst, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, Biostat Branch, Bethesda, MD USA. [Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Weissfeld, Joel L.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Yokochi, Lance A.] Pacific Hlth Res Inst, Honolulu, HI USA. [Zieglerfor, Regina G.] Natl Canc Inst, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, Off Director, Bethesda, MD USA. [Hayes, Richard B.] Natl Canc Inst, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, Occupat & Environm Epidemiol Branch, Bethesda, MD USA. RP Millen, AE (reprint author), SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Farber Hall,Room 270, Buffalo, NY 14214 USA. EM aemillen@buffalo.edu NR 73 TC 48 Z9 50 U1 1 U2 11 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 2007 VL 86 IS 6 BP 1754 EP 1764 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 240GN UT WOS:000251575500026 PM 18065596 ER PT J AU Park, Y Mitrou, PN Kipnis, V Hollenbeck, A Schatzkin, A Leitzmann, MF AF Park, Yikyung Mitrou, Panagiota N. Kipnis, Victor Hollenbeck, Albert Schatzkin, Arthur Leitzmann, Michael F. TI Calcium, dairy foods, and risk of incident and fatal prostate cancer - The NIH-AARP diet and health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE calcium; dairy products; prostatic neoplasms ID VITAMIN-D; SUBSEQUENT DEVELOPMENT; NATIONAL INSTITUTES; ANIMAL PRODUCTS; UNITED-STATES; COHORT; METAANALYSIS; MEN; SUPPLEMENTATION; CONSUMPTION AB Calcium and dairy foods in relation to prostate cancer were examined in the National Institutes of Health (NIH)-AARP (formerly known as the American Association of Retired Persons) Diet and Health Study (1995/1996-2001). Diet was assessed with a food frequency questionnaire at baseline. Multivariate relative risks and 95% confidence intervals were estimated by Cox regression. During up to 6 years of follow-up (n = 293,888), the authors identified 10,180 total prostate cancer cases (8,754 nonadvanced, 1,426 advanced, and 178 fatal cases). Total and supplemental calcium were unrelated to total and nonadvanced prostate cancer. However, a statistically nonsignificant positive association with total calcium was observed for advanced (>= 2,000 vs. 500-< 750 mg/day: relative risk (RR) = 1.25, 95% confidence interval (CI): 0.91, 1.71; p(trend) = 0.06) and fatal (>= 1,000 vs. 500-< 750 mg/day: RR = 1.39, 95% CI: 0.92, 2.09; p(trend) = 0.10) prostate cancer. Skim milk, but not other dairy foods, was associated with increased risk of advanced prostate cancer (>= 2 vs. zero servings/day: RR = 1.23, 95% CI: 0.99, 1.54; p(trend) = 0.01). In contrast, calcium from nondairy foods was associated with lower risk of nonadvanced prostate cancer (>= 600 vs. < 250 mg/day: RR = 0.82, 95% CI: 0.68, 0.99; p(trend) = 0.04). Although the authors cannot definitively rule out a weak association for aggressive prostate cancer, their findings do not provide strong support for the hypothesis that calcium and dairy foods increase prostate cancer risk. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD USA. Natl Canc Ctr, Div Canc Prevent, Bethesda, MD USA. AARP, Washington, DC USA. RP Park, Y (reprint author), Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20852 USA. EM parkyik@mail.nih.gov OI Park, Yikyung/0000-0002-6281-489X FU Intramural NIH HHS NR 36 TC 50 Z9 50 U1 4 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2007 VL 166 IS 11 BP 1270 EP 1279 DI 10.1093/aje/kwm268 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 232QN UT WOS:000251034300007 PM 18000020 ER PT J AU Stevens, J Murray, DM Baggett, CD Elder, JP Lohman, TG Lytle, LA Pate, RR Pratt, CA Treuth, MS Webber, LS Young, DR AF Stevens, June Murray, David M. Baggett, Chris D. Elder, John P. Lohman, Timothy G. Lytle, Leslie A. Pate, Russell R. Pratt, Charlotte A. Treuth, Margarita S. Webber, Larry S. Young, Deborah R. TI Objectively assessed associations between physical activity and body composition in middle-school girls - The trial of activity for adolescent girls SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adipose tissue; adolescent; anthropometry; body composition; body mass index; exercise; growth; longitudinal studies ID FRAMINGHAM CHILDRENS; ENERGY-EXPENDITURE; NHLBI GROWTH; OBESITY; HEALTH; ACCELEROMETRY; ADIPOSITY; PRESCHOOL; FATNESS; LEVEL AB Declining levels of physical activity probably contribute to the increasing prevalence of overweight in US youth. In this study, the authors examined cross-sectional and longitudinal associations between physical activity and body composition in sixth- and eighth-grade girls. In 2003, girls were recruited from six US states as part of the Trial of Activity for Adolescent Girls. Physical activity was measured using 6 days of accelerometry, and percentage of body fat was calculated using an age- and ethnicity-specific prediction equation. Sixth-grade girls with an average of 12.8 minutes of moderate-to-vigorous physical activity (MVPA) per day (15th percentile) were 2.3 times (95% confidence interval: 1.52, 3.44) more likely to be overweight than girls with 34.7 minutes of MVPA per day (85th percentile), and their percent body fat was 2.64 percentage points greater (95% confidence interval: 1.79, 3.50). Longitudinal analyses showed that percent body fat increased 0.28 percentage points less in girls with a 6.2-minute increase in MVPA than in girls with a 4.5-minute decrease (85th and 15th percentiles of change). Associations between MVPA in sixth grade and incidence of overweight in eighth grade were not detected. More population-based research using objective physical activity and body composition measurements is needed to make evidence-based physical activity recommendations for US youth. C1 Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Ohio State Univ, Sch Publ Hlth, Div Epidemiol, Columbus, OH USA. San Diego State Univ, Grad Sch Publ Hlth, Dept Hlth Promot & Behav Sci, San Diego, CA USA. Univ Arizona, Coll Med, Dept Physiol, Tucson, AZ USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN USA. Univ S Carolina, Arnold Sch Publ Sch, Dept Exercise Sci, Columbia, SC USA. NHLBI, Div Prevent & Populat Sci, Bethesda, MD USA. Johns Hopkins Univ, Ctr Human Nutr, Blooming Sch Publ Hlth, Baltimore, MD USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA USA. Univ Maryland, Coll Hlth & Human Performance, Dept Kinesiol, College Pk, MD USA. RP Stevens, J (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Nutr, CB 7400, Chapel Hill, NC 27599 USA. EM June_stevens@unc.edu FU NHLBI NIH HHS [HL-66852, U01 HL066853-07, U01 HL066845, HL-066856, HL-066853, U01 HL066857, U01 HL066858, HL-066857, U01 HL066852, U01 HL066855, U01HL-066845, U01 HL066856, U01 HL066853, HL-066858, HL-066855] NR 30 TC 51 Z9 51 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2007 VL 166 IS 11 BP 1298 EP 1305 DI 10.1093/aje/kwm202 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 232QN UT WOS:000251034300010 PM 17855391 ER PT J AU Hassan, MM Bondy, ML Wolff, RA Abbruzzese, JL Vauthey, JN Pisters, PW Evans, DB Khan, R Chou, TH Lenzi, R Jiao, L Li, DH AF Hassan, Manal M. Bondy, Melissa L. Wolff, Robert A. Abbruzzese, James L. Vauthey, Jean-Nicolas Pisters, Peter W. Evans, Douglas B. Khan, Rabia Chou, Ta-Hsu Lenzi, Renato Jiao, Li Li, Donghui TI Risk factors for pancreatic cancer: Case-control study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID FRANCISCO-BAY AREA; DIABETES-MELLITUS; CIGARETTE-SMOKING; ALCOHOL; CARCINOMA; WOMEN; INSULIN; CHOLECYSTECTOMY; EPIDEMIOLOGY; ASSOCIATION AB OBJECTIVES: Although cigarette smoking is the most well-established environmental risk factor for pancreatic cancer, the interaction between smoking and other risk factors has not been assessed. We evaluated the independent effects of multiple risk factors for pancreatic cancer and determined whether the magnitude of cigarette smoking was modified by other risk factors in men and women. METHODS: We conducted a hospital-based case-control study involving 808 patients with pathologically diagnosed pancreatic cancer and 808 healthy frequency-matched controls. Information on risk factors was collected by personal interview, and unconditional logistic regression was used to determine adjusted odds ratios (AORs) by the maximum-likelihood method. RESULTS: Cigarette smoking, family history of pancreatic cancer, heavy alcohol consumption (> 60 mL ethanol/day), diabetes mellitus, and history of pancreatitis were significant risk factors for pancreatic cancer. We found synergistic interactions between cigarette smoking and family history of pancreatic cancer (AOR 12.8, 95% confidence interval [CI] 1.6-108.9) and diabetes mellitus (AOR 9.3, 95% CI 2.0-44.1) in women, according to an additive model. Approximately 23%, 9%, 3%, and 5% of pancreatic cancer cases in this study were related to cigarette smoking, diabetes mellitus, heavy alcohol consumption, and family history of pancreatic cancer, respectively. CONCLUSIONS: The significant synergy between these risk factors suggests a common pathway for carcinogenesis of the pancreas. Determining the underlying mechanisms for such synergies may lead to the development of pancreatic cancer prevention strategies for high-risk individuals. C1 Univ Texas MD Anderson Canc Ctr Houston, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr Houston, Dept Epidemiol, Houston, TX USA. Univ Texas MD Anderson Canc Ctr Houston, Dept Surg Oncol, Houston, TX USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Rockville, MD USA. RP Hassan, MM (reprint author), Univ Texas MD Anderson Canc Ctr Houston, Dept Gastrointestinal Med Oncol, 1515 Holcombe Blvd,Unit 426, Houston, TX 77030 USA. FU NCI NIH HHS [R01 CA098380-04, R01 CA098380, R01 CA098380-01A2, R01 CA098380-02, R01 CA098380-03, R01 CA98380]; PHS HHS [P20 101936] NR 81 TC 146 Z9 158 U1 0 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2007 VL 102 IS 12 BP 2696 EP 2707 DI 10.1111/j.1572-0241.2007.01510.x PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 235QL UT WOS:000251249300015 PM 17764494 ER PT J AU Rao, VK Dowdell, KC Dale, JK Dugan, F Pesnicak, L Bi, LL Hoffmann, V Penzak, S Avila, NA Fleisher, TA Puck, JM Straus, SE AF Rao, V. Koneti Dowdell, Kennichi C. Dale, Janet K. Dugan, Faith Pesnicak, Lesley Bi, Lilia L. Hoffmann, Victoria Penzak, Scott Avila, Nilo A. Fleisher, Thomas A. Puck, Jennifer M. Straus, Stephen E. TI Pyrimethamine treatment does not ameliorate lymphoproliferation or autoimmune disease in MRL/Ipr-/- mice or In patients with autoimmune lymphoproliferative syndrome SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID LYMPHOCYTE APOPTOSIS; MYCOPHENOLATE-MOFETIL; SULFADOXINE; DISORDER; INFECTION; FEATURES; DEFECTS; MALARIA; DRUG AB Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder of lymphocyte apoptosis leading to childhood onset of marked lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias, and increased risk of lymphoma. Most cases are associated with heterozygous mutations in the gene encoding Fas protein. Prolonged use of immunosuppressive drugs that do ameliorate its autolimmune complications fail to consistently lessen lymphoproliferation in ALPS. A case series had described children with ALPS, whose spleens (SPL) and lymph nodes decreased in size when treated weekly with pyrimethamine and sulfadoxine; parallel in vitro studies showed only pyrimethamine to promote apoptosis. On the basis of that experience, we undertook additional in vitro lymphocyte apoptosis assays, and measured SPL Weights, lymphocyte numbers, and immunophenotypes in Fas-deficient MRL/Ipr-/- mice to gain further insights into the utility of combined pyrimethamine/sulfadoxine or pyrimethamine alone. Moreover, seven children with ALPS enrolled in a study of escalating dose of pyrimethamine alone given twice weekly for 12 weeks to determine if their lymphadenopathy and/or splenomegaly would diminish, as assessed by standardized computerized tomography. Neither pyrimethamine alone or with sulfadoxine in the MRL/Ipr-/- mice, nor pyrimethamine alone in ALPS patients proved efficacious. We conclude that these drugs do not warrant further use empirically or as part of clinical trials in ALPS Type la as a lympholytic agent. Am. J. Hematol. 82:1049-1055, 2007. (c) Published 2007 Wiley-Liss, Inc. C1 NIH, NIAID, LCID, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NIH, Dept Vet Resources, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Rao, VK (reprint author), NIH, NIAID, LCID, 10 Ctr Dr,Room 11N234, Bethesda, MD 20892 USA. EM koneti@nih.gov FU Intramural NIH HHS NR 26 TC 11 Z9 11 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 2007 VL 82 IS 12 BP 1049 EP 1055 DI 10.1002/ajh.21007 PG 7 WC Hematology SC Hematology GA 235YU UT WOS:000251271000004 PM 17674358 ER PT J AU Hoppin, JA Valcin, M Henneberger, PK Kullman, GJ Umbach, DM London, SJ Alavanja, MCR Sandier, DP AF Hoppin, Jane A. Valcin, Martin Henneberger, Paul K. Kullman, Greg J. Umbach, David M. London, Stephanie J. Alavanja, Michael C. R. Sandier, Dale P. TI Pesticide use and chronic bronchitis among farmers in the agricultural health study SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE respiratory disease; agricultural exposures; pesticides; occupational exposure ID OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC RESPIRATORY SYMPTOMS; LUNG-FUNCTION; CONFINEMENT BUILDINGS; APPLICATORS; EXPOSURE; EPIDEMIOLOGY; PREVALENCE; OCCUPATION; SMOKING AB Background Farmers have increased risk for chronic bronchitis. Few investigators have considered pesticides. Methods We evaluated pesticides as risk factors for chronic bronchitis using the Agricultural Health Study enrollment data on lifetime pesticide use and history of doctor-diagnosed chronic bronchitis from 20,908 private pesticide applicators, primarily farmers. Results A total of 654 farmers (3%) reported chronic bronchitis diagnosed after age 19. After adjustment for correlated pesticides as well as confounders, 11 pesticides were significantly associated with chronic bronchitis. Heptachlor use had the highest odds ratio (OR = 1.50, 95% Confidence Interval (CI) = 1.19, 1.89). Increased prevalence for chronic bronchitis was also seen for individuals who had a history of a high pesticide exposure event (OR = 1.85, 95% CI = 1.51, 2.25) and for those who also applied pesticides in off-farm jobs (OR = 1.40, 95% CI = 1.04,1.88). Co-morbid asthma and current farm activities did not explain these results. Conclusions These results provide preliminary evidence that pesticide use may increase chronic bronchitis prevalence. Am. J. Ind. Med. 50:969-979,2007. (c) 2007 Wiley-Liss, Inc. C1 NIEHS, NIH, DHHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Field Studies Branch, Morgantown, WV USA. NIH, NIEHS, DHHS, Biostat Branch, Res Triangle Pk, NC USA. NIH, NCI, DHHS, Occupat Epidemiol Branch, Rockville, MD USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov OI Sandler, Dale/0000-0002-6776-0018; London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS [Z01 ES049030-11] NR 44 TC 37 Z9 39 U1 1 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 2007 VL 50 IS 12 BP 969 EP 979 DI 10.1002/ajim.20523 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 234GW UT WOS:000251149700012 PM 17975796 ER PT J AU Dhingra, R Gona, P Nam, BH D'Agostino, RB Wilson, PWF Benjamin, EJ O'Donnell, CJ AF Dhingra, Ravi Gona, Philimon Nam, Byung-Ho D'Agostino, Ralph B. Wilson, Peter W. F. Benjamin, Emelia J. O'Donnell, Christopher J. TI C-reactive protein, inflammatory conditions, and cardiovascular disease risk SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc DE arthritis; C-reactive protein; cardiovascular disease; cohort study; inflammation ID CORONARY-HEART-DISEASE; PUBLIC-HEALTH PRACTICE; RHEUMATOID-ARTHRITIS; PLASMA-CONCENTRATION; TISSUE FACTOR; MARKERS; MEN; PREDICTION; WOMEN; SERUM AB BACKGROUND: It is uncertain to what extent high C-reactive protein (CRP) concentrations reflect the presence of inflammatory conditions in the community. METHODS: We evaluated 3782 Framingham Offspring Study participants (mean age 55 years; 52% women) free of baseline cardiovascular disease. Logistic regression models examined the prevalence of common inflammatory conditions by CRP categories, while a separate matched case-referent analysis evaluated the prevalence of uncommon inflammatory conditions. Cox models were used to assess the influence of common inflammatory conditions on relations between CRP and incident cardiovascular disease. RESULTS: Common inflammatory conditions were reported by nearly half of the participants; these individuals were more likely to have markedly high CRP concentrations (> 10 mg/L, P for trend =.001). In multivariable models, there were increased odds of having at least one common inflammatory condition with CRP concentrations of 1-3.0, 3.01-10, and > 10 mg/ L, compared with the referent category (< 1 mg/ L); the respective odds ratios with 95% confidence intervals were 1.41 (1.07-1.86), 1.45 (1.07-1.98), and 1.64 (1.09-2.47) in men, and 1.08 (0.82-1.43), 1.07 (0.80-1.44), and 1.38 (0.97-1.96) in women. In case-referent analyses, uncommon inflammatory conditions were more common in individuals with CRP > 10 mg/L compared with those with CRP < 1 mg/ L (12.1% vs 6.6%; P=.0001). In multivariable models, higher CRP categories were not associated with incident cardiovascular disease, and with additional adjustment for inflammatory conditions, results remained unchanged. CONCLUSION: There is high prevalence of common and uncommon inflammatory conditions in individuals with high CRP concentrations. Higher CRP concentrations should be interpreted with caution in cardiovascular disease risk assessment. (c) 2007 Elsevier Inc. All rights reserved. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Alice Peck Day Mem Hosp, Lebanon, NH USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Med Univ S Carolina, Gen Clin Res Ctr, Charleston, SC 29425 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave 2, Framingham, MA 01702 USA. EM codonnell@partners.org OI Benjamin, Emelia/0000-0003-4076-2336 FU Intramural NIH HHS [Z99 HL999999]; NHLBI NIH HHS [N01 HC 25195, N01 HC025195, R01 HL 073272 01, R01 HL 076784, R01 HL 64753, R01 HL073272, R01 HL076784] NR 40 TC 36 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2007 VL 120 IS 12 BP 1054 EP 1062 DI 10.1016/j.amjmed.2007.08.037 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 238ZI UT WOS:000251486700010 PM 18060926 ER PT J AU Semba, RD Ferrucci, L Sun, K Walston, J Varadhan, R Guralnik, JM Fried, LP AF Semba, Richard D. Ferrucci, Luigi Sun, Kai Walston, Jeremy Varadhan, Ravi Guralnik, Jack M. Fried, Linda P. TI Oxidative stress and severe walking disability among older women SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE aging; disability; oxidative stress; protein carbonyls; walking ID HUMAN SKELETAL-MUSCLE; PROTEIN OXIDATION; DAMAGE; BIOMARKERS; CONSUMPTION; SARCOPENIA; INCREASES; MARKERS; OBESITY; DNA AB BACKGROUND: Oxidative stress has been implicated in sarcopenia and the loss of muscle strength with aging, but the relationship between oxidative stress and decrease in muscle strength and physical performance has not been well characterized. Serum protein carbonyls are markers of oxidative damage to proteins and are caused by oxidative stress. METHODS: Serum protein carbonyls were measured at baseline and compared with a decrease in walking speed and development of severe walking disability ( inability to walk or walking speed < 0.4 m/sec) over 36 months of follow-up in 545 moderately to severely disabled women, aged >= 65 years, living in the community in Baltimore, Maryland ( the Women's Health and Aging Study I). RESULTS: After adjusting for age, body mass index, smoking, and chronic diseases, log e protein carbonyls (nmol/mg) were associated with a decrease in walking speed over 36 months (P=.002). During follow-up, 154 women (28.2%) developed severe walking disability. After adjusting for the same potential confounders, log e protein carbonyls were associated with incident severe walking disability ( hazards ratio 1.42, 95% confidence interval, 1.02-1.98, P=.037). CONCLUSION: High oxidative stress, as indicated by oxidative damage to proteins, is an independent predictor of decrease in walking speed and progression to severe walking disability among older women living in the community. (c) 2007 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. EM rdsemba@jhmi.edu FU Intramural NIH HHS [Z99 AG999999]; NCRR NIH HHS [M01 RR000722]; NIA NIH HHS [R01 AG027012, N01 AG012112, N01-AG12112, R01 AG027012-03, R37 AG019905] NR 30 TC 48 Z9 48 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2007 VL 120 IS 12 BP 1084 EP 1089 DI 10.1016/j.amjmed.2007.07.028 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 238ZI UT WOS:000251486700014 PM 18060930 ER PT J AU Aagaard-Tillery, K AF Aagaard-Tillery, Kjersti TI Hazardous air pollutants & risk of adverse pregnancy outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Aagaard-Tillery, Kjersti] NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 670 BP S192 EP S192 DI 10.1016/j.ajog.2007.10.697 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500662 ER PT J AU Bakhshi, T AF Bakhshi, Tiki TI Maternal and neonatal outcomes of repeat cesarean delivery in women with a prior classical versus low transverse uterine, incision SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Bakhshi, Tiki] NICHD, MFMU Network, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 234 BP S77 EP S77 DI 10.1016/j.ajog.2007.10.248 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500234 ER PT J AU Casey, B Spong, C McIntire, D Leveno, K Cunningham, FG AF Casey, Brian Spong, Catherine McIntire, Donald Leveno, Kenneth Cunningham, F. Gary TI Parity in relation to antithyroid peroxidase antibodies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Casey, Brian; McIntire, Donald; Leveno, Kenneth; Cunningham, F. Gary] Univ Texas SW Med Ctr Dallas, Dallas, TX USA. [Spong, Catherine] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 425 BP S127 EP S127 DI 10.1016/j.ajog.2007.10.443 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500419 ER PT J AU Casey, B Spong, C McIntire, D Leveno, K Cunningham, FG AF Casey, Brian Spong, Catherine McIntire, Donald Leveno, Kenneth Cunningham, F. Gary TI Pregnancy outcomes in women with antithyroid peroxidase antibodies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 Univ Texas SW Med Ctr Dallas, Dallas, TX USA. [Spong, Catherine] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 424 BP S126 EP S126 DI 10.1016/j.ajog.2007.10.442 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500418 ER PT J AU Contag, S AF Contag, Stephen TI Operative vaginal delivery versus cesarean delivery in the second stage of labor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Contag, Stephen] NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 244 BP S79 EP S79 DI 10.1016/j.ajog.2007.10.258 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500244 ER PT J AU Erez, O Romero, R Hoppensteadt, D Fareed, J Chaiworapongsa, T Kusanovic, JP Mazaki-Tovi, S Gotsch, F Than, NG Vaisbuch, E Kim, CJ Espinoza, J Mittal, P Nhan-Chang, CL Hamill, N Mazor, M Hassan, S AF Erez, Offer Romero, Roberto Hoppensteadt, Debra Fareed, Jawed Chaiworapongsa, Tinnakorn Kusanovic, Juan Pedro Mazaki-Tovi, Shali Gotsch, Francesca Than, Nandor Gabor Vaisbuch, Edi Kim, Chong Jai Espinoza, Jimmy Mittal, Pooja Nhan-Chang, Chia-Ling Hamill, Neil Mazor, Moshe Hassan, Sonia TI Is premature labor a state of platelet activation? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Erez, Offer; Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Than, Nandor Gabor; Vaisbuch, Edi] NICHD, NIH, DHHS, Perinatol Res Unit, Detroit, MI USA. [Hoppensteadt, Debra; Fareed, Jawed] Loyola Univ Hlth Syst, Dept Pathol, Chicago, IL USA. [Chaiworapongsa, Tinnakorn; Mazaki-Tovi, Shali; Espinoza, Jimmy; Mittal, Pooja; Nhan-Chang, Chia-Ling; Hamill, Neil; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. [Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI USA. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ Med Ctr, Dept Obstet & Gynecol, Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 123 BP S47 EP S47 DI 10.1016/j.ajog.2007.10.134 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500125 ER PT J AU Espinoza, J Romero, R Kusanovic, JP Gotsch, F Mittal, P Erez, O Than, NG Kim, CJ Edwin, SS Mazakitovi, S Vaisbuch, E Hassan, S AF Espinoza, Jimmy Romero, Roberto Kusanovic, Juan Pedro Gotsch, Francesca Mittal, Pooja Erez, Offer Than, Nandor Gabor Kim, Chong Jai Edwin, Samuel S. Mazakitovi, Shau Vaisbuch, Edi Hassan, Sonia TI Maternal plasma concentrations of placental growth factor (PLGF) and soluble endoglin (S-ENG) in the second trimester identify patients destined to develop early-onset preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Espinoza, Jimmy; Mittal, Pooja; Mazakitovi, Shau; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Erez, Offer; Than, Nandor Gabor; Edwin, Samuel S.; Vaisbuch, Edi] NICHD, NIH, DHHS, Perinatol Branch, Detroit, MI USA. [Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48202 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 463 BP S136 EP S136 DI 10.1016/j.ajog.2007.10.482 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500456 ER PT J AU Gotsch, F Romero, R Erez, O Espinoza, J Kusanovic, JP Mittal, P Mazaki-Tovi, S Kim, CJ Kim, JS Edwin, SS Nhan-Chang, CL Hamill, N Friel, L Vaisbuch, E Than, NG Yoon, BH Hassan, S AF Gotsch, Francesca Romero, Roberto Erez, Offer Espinoza, Jimmy Kusanovic, Juan Pedro Mittal, Pooja Mazaki-Tovi, Shali Kim, Chong Jai Kim, Jung-Sun Edwin, Samuel S. Nhan-Chang, Chia-Ling Hamill, Neil Friel, Lara Vaisbuch, Edi Than, Nandor Gabor Yoon, Bo Hyun Hassan, Sonia TI Evidence of the involvement of caspase-1 under physiologic and pathologic cellular stress during human pregnancy: A link between the inflammasome and parturition SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Gotsch, Francesca; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Edwin, Samuel S.; Vaisbuch, Edi; Than, Nandor Gabor] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Espinoza, Jimmy; Mittal, Pooja; Mazaki-Tovi, Shali; Nhan-Chang, Chia-Ling; Hamill, Neil; Friel, Lara; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Kim, Chong Jai; Kim, Jung-Sun] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Yoon, Bo Hyun] Seoul Natl Univ Hosp, Seoul 110744, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 304 BP S95 EP S95 DI 10.1016/j.ajog.2007.10.319 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500304 ER PT J AU Hamill, N Romero, R Kusanovic, JP Gotsch, F Edwin, SS Erez, O Than, NG Mittal, P Espinoza, J Friel, LA Vaisbuch, E Mazaki-Tovi, S Hassan, S AF Hamill, Neil Romero, Roberto Kusanovic, Juan Pedro Gotsch, Francesca Edwin, Samuel S. Erez, Offer Than, Nandor Gabor Mittal, Pooja Espinoza, Jimmy Friel, Lara A. Vaisbuch, Edi Mazaki-Tovi, Shali Hassan, Sonia TI Exodus 1 (CCL20) is a chemokine involved in spontaneous parturition at term as well as in preterm labor in the presence or absence of infection/inflammation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Hamill, Neil; Mittal, Pooja; Espinoza, Jimmy; Friel, Lara A.; Mazaki-Tovi, Shali; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Edwin, Samuel S.; Erez, Offer; Than, Nandor Gabor; Vaisbuch, Edi] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 198 BP S66 EP S66 DI 10.1016/j.ajog.2007.10.211 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500199 ER PT J AU Harper, M AF Harper, Margaret TI Randomized controlled trial of omega-3 fatty acid supplementation for recurrent preterm birth prevention SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Harper, Margaret] NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 3 BP S2 EP S2 DI 10.1016/j.ajog.2007.10.004 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500006 ER PT J AU Hebert, MF Naraharisett, SB Ma, X Krudys, KM Umans, J Hankins, GDV Caritis, S Miodovnik, M Mattison, DR Unadkat, J Easterling, TR Vicini, P AF Hebert, Mary F. Naraharisett, Suresh Babu Ma, Xiaosu Krudys, Kevin M. Umans, Jason Hankins, Gary D. V. Caritis, Steve Miodovnik, Menachem Mattison, Donald R. Unadkat, Jashvant Easterling, Thomas R. Vicini, Paolo TI Are we guessing glyburide dosage in the treatment of gestational diabetes (GDM)? The pharmacological evidence for better clinical practice SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Hebert, Mary F.; Naraharisett, Suresh Babu; Ma, Xiaosu; Krudys, Kevin M.; Unadkat, Jashvant; Easterling, Thomas R.; Vicini, Paolo] Univ Washington, Seattle, WA 98195 USA. [Umans, Jason; Miodovnik, Menachem] Georgetown Univ, Med Ctr, Washington Hosp Ctr, MedStar Res Inst, Washington, DC 20007 USA. [Hankins, Gary D. V.] Univ Texas Med Branch, Galveston, TX USA. [Caritis, Steve] Univ Pittsburgh, Pittsburgh, PA USA. [Mattison, Donald R.] NIH, Bethesda, MD 20892 USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 53 BP S25 EP S25 DI 10.1016/j.ajog.2007.10.060 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500056 ER EF