FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Auld, DS Southall, NT Jadhav, A Johnson, RL Diller, DJ Simeonov, A Austin, CP Inglese, J AF Auld, Douglas S. Southall, Noel T. Jadhav, Ajit Johnson, Ronald L. Diller, David J. Simeonov, Anton Austin, Christopher P. Inglese, James TI Characterization of chemical libraries for luciferase inhibitory activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; FIREFLY LUCIFERASE; KINASE INHIBITORS; TYROSINE KINASE; IN-VIVO; BIOLUMINESCENCE; MECHANISM; ASSAYS; IDENTIFICATION; RESVERATROL AB To aid in the interpretation of high-throughput screening (HTS) results derived from luciferase-based assays, we used quantitative HTS, an approach that defines the concentration -response behavior of each library sample, to profile the ATP-dependent luciferase from Photinus pyralis against more than 70 000 samples. We found that approximately 3% of the library was active, containing only compounds with inhibitory concentration -responses, of which 681 (0.9%) exhibited IC50 < 10 mu M. Representative compounds were shown to inhibit purified P. pyralis as well as several commercial luciferase-based detection reagents but were found to be largely inactive against Renilla reniformis luciferase. Light attenuation by the samples was also examined and found to be more prominent in the blue-shifted bioluminescence produced by R. reniformis luciferase than in the bioluminescence produced by P. pyralis luciferase. We describe the structure- activity relationship of the luciferase inhibitors and discuss the use of this data in the interpretation of HTS results and configuration of luciferase-based assays. C1 [Auld, Douglas S.; Southall, Noel T.; Jadhav, Ajit; Johnson, Ronald L.; Simeonov, Anton; Austin, Christopher P.; Inglese, James] NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Diller, David J.] Pharmacopeia Inc, Princeton, NJ 08543 USA. RP Inglese, J (reprint author), NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. EM jinglese@mail.nih.gov RI Southall, Noel/H-8991-2012 OI Southall, Noel/0000-0003-4500-880X FU Intramural NIH HHS NR 36 TC 106 Z9 106 U1 1 U2 18 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 APR 24 PY 2008 VL 51 IS 8 BP 2372 EP 2386 DI 10.1021/jm701302v PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 290EH UT WOS:000255105600007 PM 18363348 ER PT J AU Tidgewell, K Groer, CE Harding, WW Lozama, A Schmidt, M Marquam, A Hiemstra, J Partilla, JS Dersch, CM Rothman, RB Bohn, LM Prisinzano, TE AF Tidgewell, Kevin Groer, Chad E. Harding, Wayne W. Lozama, Anthony Schmidt, Matthew Marquam, Alfred Hiemstra, Jessica Partilla, John S. Dersch, Christina M. Rothman, Richard B. Bohn, Laura M. Prisinzano, Thomas E. TI Herkinorin analogues with differential beta-arrestin-2 interactions SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID KAPPA-OPIOID-RECEPTOR; PLANT-DERIVED HALLUCINOGEN; PROTEIN-COUPLED RECEPTORS; SALVINORIN-A ANALOGS; SALVIA-DIVINORUM; NEOCLERODANE DITERPENES; MEDIATED PHENOMENA; NATURAL-PRODUCTS; DRUG DISCOVERY; BETA-ARRESTINS AB Salvinorin A is a psychoactive natural product that has been found to be a potent and selective kappa opioid receptor agonist in vitro and in vivo. The activity of salvinorin A is unusual compared to other opioids such as morphine in that it mediates potent kappa opioid receptor signaling yet leads to less receptor downregulation than observed with other kappa agonists. Our initial chemical modifications of salvinorin A have yielded one analogue, herkinorin (1c), with high affinity at the mu OR. We recently reported that 1c does not promote the recruitment of beta-arrestin-2 to the mu OR or receptor internalization. Here we describe three new derivatives of 1c (3c, 3f, and 3i) with similar properties and one, benzamide 7b, that promotes recruitment of beta-arrestin-2 to the mu OR and receptor internalization. When the important role mu opioid receptor regulation plays in determining physiological responsiveness to opioid narcotics is considered,mu opioids derived from salvinorin A may offer a unique template for the development of functionally selective mu opioid receptor-ligands with the ability to produce analgesia while limiting adverse side effects. C1 [Tidgewell, Kevin; Harding, Wayne W.; Lozama, Anthony; Schmidt, Matthew; Marquam, Alfred; Hiemstra, Jessica; Prisinzano, Thomas E.] Univ Iowa, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. [Groer, Chad E.; Bohn, Laura M.] Ohio State Univ, Coll Med, Dept Pharmacol, Columbus, OH 43210 USA. [Groer, Chad E.; Bohn, Laura M.] Ohio State Univ, Coll Med, Dept Psychiat, Columbus, OH 43210 USA. [Marquam, Alfred; Prisinzano, Thomas E.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. [Partilla, John S.; Dersch, Christina M.; Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, IRP, DHHS,NIH, Baltimore, MD 21224 USA. RP Prisinzano, TE (reprint author), Univ Iowa, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. EM prisinza@ku.edu RI Prisinzano, Thomas/B-7877-2010; Bohn, Laura/A-7483-2014; OI Bohn, Laura/0000-0002-6474-8179; Tidgewell , Kevin/0000-0002-0501-2604 FU Intramural NIH HHS; NIDA NIH HHS [R01 DA018860, K01 DA014600, K01 DA014600-01, K01 DA014600-06, K01DA14600, R01 DA018151, R01 DA018151-01A2, R01 DA018151-02S1, R01 DA018860-01, R01 DA018860-04, R01DA018151, R01DA018151S1, R01DA18860]; NIGMS NIH HHS [T32 GM067795] NR 53 TC 32 Z9 33 U1 0 U2 4 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 APR 24 PY 2008 VL 51 IS 8 BP 2421 EP 2431 DI 10.1021/jm701162g PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 290EH UT WOS:000255105600011 PM 18380425 ER PT J AU Babaoglu, K Simeonov, A Lrwin, JJ Nelson, ME Feng, B Thomas, CJ Cancian, L Costi, MP Maltby, DA Jadhav, A Inglese, J Austin, CP Shoichet, BK AF Babaoglu, Kerim Simeonov, Anton Lrwin, John J. Nelson, Michael E. Feng, Brian Thomas, Craig J. Cancian, Laura Costi, M. Paola Maltby, David A. Jadhav, Ajit Inglese, James Austin, Christopher P. Shoichet, Brian K. TI Comprehensive mechanistic analysis of hits from high-throughput and docking screens against beta-lactamase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DRUG DISCOVERY; PROMISCUOUS INHIBITORS; CHEMICAL LIBRARIES; LEAD DISCOVERY; IDENTIFICATION; MOLECULES; DATABASE; BIOLOGY; ASSAYS; MODEL AB High-throughput screening (HTS) is widely used in drug discovery. Especially for screens of unbiased libraries, false positives can dominate "hit lists"; their origins are much debated. Here we determine the mechanism of every active hit from a screen of 70,563 unbiased molecules against P-lactamase using quantitative HTS (qHTS). Of the 1274 initial inhibitors, 95% were detergent- sensitive and were classified as aggregators. Among the 70 remaining were 25 potent, covalent-acting beta-lactams. Mass spectra, counter-screens, and crystallography identified 12 as promiscuous covalent inhibitors. The remaining 33 were either aggregators or irreproducible. No specific reversible inhibitors were found. We turned to molecular docking to prioritize molecules from the same library for testing at higher concentrations. Of 16 tested, 2 were modest inhibitors. Subsequent X-ray structures corresponded to the docking prediction. Analog synthesis improved affinity to 8 mu M. These results suggest that it may be the physical behavior of organic molecules, not their reactivity, that accounts for most screening artifacts. Structure-based methods may prioritize weak-but-novel chemotypes in unbiased library screens. C1 [Simeonov, Anton; Nelson, Michael E.; Thomas, Craig J.; Jadhav, Ajit; Inglese, James; Austin, Christopher P.] NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Babaoglu, Kerim; Lrwin, John J.; Feng, Brian; Shoichet, Brian K.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA. [Maltby, David A.] Univ Calif San Francisco, Dept Pharmaceut Chem, Mass Spect Facil, San Francisco, CA 94143 USA. [Cancian, Laura; Costi, M. Paola] Univ Modena & Reggio Emilia, Dipartimento Sci Farmaceut, I-41100 Modena, Italy. RP Austin, CP (reprint author), NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. EM austinc@mail.nih.gov; shoichet@cgl.ucsf.edu RI Costi, Maria Paola/F-4747-2015; OI Costi, Maria Paola/0000-0002-0443-5402; Irwin, John/0000-0002-1195-6417 FU NIGMS NIH HHS [GM71630, F32 GM076883, GM076883, GM59957, R01 GM059957, R01 GM071630, R01 GM071630-04A1]; PHS HHS [BRTP 01614] NR 46 TC 90 Z9 92 U1 3 U2 12 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 APR 24 PY 2008 VL 51 IS 8 BP 2502 EP 2511 DI 10.1021/jm701500e PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 290EH UT WOS:000255105600019 PM 18333608 ER PT J AU Richards, S Gibbs, RA Weinstock, GM Brown, SJ Denell, R Beeman, RW Gibbs, R Bucher, G Friedrich, M Grimmelikhuijzen, CJP Klingler, M Lorenzen, MD Roth, S Schroder, R Tautz, D Zdobnov, EM Muzny, D Attaway, T Bell, S Buhay, CJ Chandrabose, MN Chavez, D Clerk-Blankenburg, KP Cree, A Dao, M Davis, C Chacko, J Dinh, H Dugan-Rocha, S Fowler, G Garner, TT Garnes, J Gnirke, A Hawes, A Hernandez, J Hines, S Holder, M Hume, J Jhangiani, SN Joshi, V Khan, ZM Jackson, L Kovar, C Kowis, A Lee, S Lewis, LR Margolis, J Morgan, M Nazareth, LV Nguyen, N Okwuonu, G Parker, D Ruiz, SJ Santibanez, J Savard, J Scherer, SE Schneider, B Sodergren, E Vattahil, S Villasana, D White, CS Wright, R Park, Y Lord, J Oppert, B Brown, S Wang, LJ Savard, J Liu, Y Worley, K Elsik, CG Reese, JT Elhaik, E Landan, G Graur, D Arensburger, P Atkinson, P Beidler, J Demuth, JP Drury, DW Du, YZ Fujiwara, H Maselli, V Osanai, M Robertson, HM Tu, Z Wang, JJ Wang, SZ Song, H Zhang, L Sodergren, E Werner, D Stanke, M Morgenstern, B Solovyev, V Kosarev, P Brown, G Chen, HC Ermolaeva, O Hlavina, W Kapustin, Y Kiryutin, B Kitts, P Maglott, D Pruitt, K Sapojnikov, V Souvorov, A Mackey, AJ Waterhouse, RM Wyder, S Zdobnov, EM Kriventseva, EV Kadowaki, T Bork, P Aranda, M Bao, RY Beermann, A Berns, N Bolognesi, R Bonneton, F Bopp, D Butts, T Chaumot, A Denell, RE Ferrier, DEK Gordon, CM Jindra, M Klingler, M Lan, Q Lattorff, HMG Laudet, V von Levetsow, C Liu, ZY Lutz, R Lynch, JA da Fonseca, RN Posnien, N Reuter, R Roth, S Schinko, JB Schmitt, C Schoppmeier, M Shippy, TD Simonnet, F Marques-Souza, H Tomoyasu, Y Trauner, J Van der Zee, M Vervoort, M Wittkopp, N Wimmer, EA Yang, XY Jones, AK Sattelle, DB Ebert, PR Nelson, D Scott, JG Muthukrishnan, S Kramer, KJ Arakane, Y Zhu, QS Hogenkamp, D Dixit, R Jiang, HB Zou, Z Marshall, J Elpidina, E Vinokurov, K Oppert, C Evans, J Lu, ZQ Zhao, PC Sumathipala, N Altincicek, B Vilcinskas, A Williams, M Hultmark, D Hetru, C Hauser, F Cazzamali, G Williamson, M Li, B Tanaka, Y Predel, R Neupert, S Schachtner, J Verleyen, P Raible, F Walden, KKO Robertson, HM Angeli, S Foret, S Schuetz, S Maleszka, R Miller, SC Grossmann, D AF Richards, Stephen Gibbs, Richard A. Weinstock, George M. Brown, Susan J. Denell, Robin Beeman, Richard W. Gibbs, Richard Bucher, Gregor Friedrich, Markus Grimmelikhuijzen, Cornelis J. P. Klingler, Martin Lorenzen, Marce D. Roth, Siegfried Schroeder, Reinhard Tautz, Diethard Zdobnov, Evgeny M. Muzny, Donna Attaway, Tony Bell, Stephanie Buhay, Christian J. Chandrabose, Mimi N. Chavez, Dean Clerk-Blankenburg, Kerstin P. Cree, Andrew Dao, Marvin Davis, Clay Chacko, Joseph Dinh, Huyen Dugan-Rocha, Shannon Fowler, Gerald Garner, Toni T. Garnes, Jeffrey Gnirke, Andreas Hawes, Alica Hernandez, Judith Hines, Sandra Holder, Michael Hume, Jennifer Jhangiani, Shalini N. Joshi, Vandita Khan, Ziad Mohid Jackson, LaRonda Kovar, Christie Kowis, Andrea Lee, Sandra Lewis, Lora R. Margolis, Jon Morgan, Margaret Nazareth, Lynne V. Nguyen, Ngoc Okwuonu, Geoffrey Parker, David Ruiz, San-Juana Santibanez, Jireh Savard, Joel Scherer, Steven E. Schneider, Brian Sodergren, Erica Vattahil, Selina Villasana, Donna White, Courtney S. Wright, Rita Park, Yoonseong Lord, Jeff Oppert, Brenda Brown, Susan Wang, Liangjiang Savard, Joel Liu, Yue Worley, Kim Elsik, Christine G. Reese, Justin T. Elhaik, Eran Landan, Giddy Graur, Dan Arensburger, Peter Atkinson, Peter Beidler, Jim Demuth, Jeffery P. Drury, Douglas W. Du, Yu-Zhou Fujiwara, Haruhiko Maselli, Vincenza Osanai, Mizuko Robertson, Hugh M. Tu, Zhijian Wang, Jian-Jun Wang, Suzhi Song, Henry Zhang, Lan Sodergren, Erica Werner, Doreen Stanke, Mario Morgenstern, Burkhard Solovyev, Victor Kosarev, Peter Brown, Garth Chen, Hsiu-Chuan Ermolaeva, Olga Hlavina, Wratko Kapustin, Yuri Kiryutin, Boris Kitts, Paul Maglott, Donna Pruitt, Kim Sapojnikov, Victor Souvorov, Alexandre Mackey, Aaron J. Waterhouse, Robert M. Wyder, Stefan Zdobnov, Evgeny M. Kriventseva, Evgenia V. Kadowaki, Tatsuhiko Bork, Peer Aranda, Manuel Bao, Riyue Beermann, Anke Berns, Nicola Bolognesi, Renata Bonneton, Francois Bopp, Daniel Butts, Thomas Chaumot, Arnaud Denell, Robin E. Ferrier, David E. K. Gordon, Cassondra M. Jindra, Marek Klingler, Martin Lan, Que Lattorff, H. Michael G. Laudet, Vincent von Levetsow, Cornelia Liu, Zhenyi Lutz, Rebekka Lynch, Jeremy A. da Fonseca, Rodrigo Nunes Posnien, Nico Reuter, Rolf Roth, Siegfried Schinko, Johannes B. Schmitt, Christian Schoppmeier, Michael Shippy, Teresa D. Simonnet, Franck Marques-Souza, Henrique Tomoyasu, Yoshinori Trauner, Jochen Van der Zee, Maurijn Vervoort, Michel Wittkopp, Nadine Wimmer, Ernst A. Yang, Xiaoyun Jones, Andrew K. Sattelle, David B. Ebert, Paul R. Nelson, David Scott, Jeffrey G. Muthukrishnan, Subbaratnam Kramer, Karl J. Arakane, Yasuyuki Zhu, Qingsong Hogenkamp, David Dixit, Radhika Jiang, Haobo Zou, Zhen Marshall, Jeremy Elpidina, Elena Vinokurov, Konstantin Oppert, Cris Evans, Jay Lu, Zhiqiang Zhao, Picheng Sumathipala, Niranji Altincicek, Boran Vilcinskas, Andreas Williams, Michael Hultmark, Dan Hetru, Charles Hauser, Frank Cazzamali, Giuseppe Williamson, Michael Li, Bin Tanaka, Yoshiaki Predel, Reinhard Neupert, Susanne Schachtner, Joachim Verleyen, Peter Raible, Florian Walden, Kimberly K. O. Robertson, Hugh M. Angeli, Sergio Foret, Sylvain Schuetz, Stefan Maleszka, Ryszard Miller, Sherry C. Grossmann, Daniela CA Tribolium Genome Sequencing Consortium TI The genome of the model beetle and pest Tribolium castaneum SO NATURE LA English DT Article ID SHORT-GERM INSECT; RED FLOUR BEETLE; DROSOPHILA-MELANOGASTER; GENE SUPERFAMILY; APIS-MELLIFERA; MESSENGER-RNA; BOMBYX-MORI; HONEY-BEE; PROTEIN; SEGMENTATION AB Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell - cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short- germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control. C1 [Richards, Stephen; Gibbs, Richard A.; Weinstock, George M.; Gibbs, Richard; Bucher, Gregor; Muzny, Donna; Attaway, Tony; Bell, Stephanie; Buhay, Christian J.; Chandrabose, Mimi N.; Chavez, Dean; Clerk-Blankenburg, Kerstin P.; Cree, Andrew; Dao, Marvin; Davis, Clay; Chacko, Joseph; Dinh, Huyen; Dugan-Rocha, Shannon; Fowler, Gerald; Garner, Toni T.; Hawes, Alica; Hernandez, Judith; Hines, Sandra; Holder, Michael; Hume, Jennifer; Jhangiani, Shalini N.; Joshi, Vandita; Khan, Ziad Mohid; Jackson, LaRonda; Kovar, Christie; Kowis, Andrea; Lee, Sandra; Lewis, Lora R.; Morgan, Margaret; Nazareth, Lynne V.; Nguyen, Ngoc; Okwuonu, Geoffrey; Parker, David; Ruiz, San-Juana; Santibanez, Jireh; Scherer, Steven E.; Schneider, Brian; Sodergren, Erica; Vattahil, Selina; Villasana, Donna; White, Courtney S.; Wright, Rita; Liu, Yue; Worley, Kim; Song, Henry; Zhang, Lan; Sodergren, Erica] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Richards, Stephen; Gibbs, Richard A.; Weinstock, George M.; Gibbs, Richard; Bucher, Gregor; Muzny, Donna; Attaway, Tony; Bell, Stephanie; Buhay, Christian J.; Chandrabose, Mimi N.; Chavez, Dean; Clerk-Blankenburg, Kerstin P.; Cree, Andrew; Dao, Marvin; Davis, Clay; Chacko, Joseph; Dinh, Huyen; Dugan-Rocha, Shannon; Fowler, Gerald; Garner, Toni T.; Hawes, Alica; Hernandez, Judith; Hines, Sandra; Holder, Michael; Hume, Jennifer; Jhangiani, Shalini N.; Joshi, Vandita; Khan, Ziad Mohid; Jackson, LaRonda; Kovar, Christie; Kowis, Andrea; Lee, Sandra; Lewis, Lora R.; Morgan, Margaret; Nazareth, Lynne V.; Nguyen, Ngoc; Okwuonu, Geoffrey; Parker, David; Ruiz, San-Juana; Santibanez, Jireh; Scherer, Steven E.; Schneider, Brian; Sodergren, Erica; Vattahil, Selina; Villasana, Donna; White, Courtney S.; Wright, Rita; Liu, Yue; Worley, Kim; Song, Henry; Zhang, Lan; Sodergren, Erica] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Brown, Susan J.; Denell, Robin; Lorenzen, Marce D.; Brown, Susan; Wang, Liangjiang; Wang, Suzhi; Bolognesi, Renata; Denell, Robin E.; Gordon, Cassondra M.; Shippy, Teresa D.; Tomoyasu, Yoshinori; Marshall, Jeremy; Miller, Sherry C.] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA. [Beeman, Richard W.; Lorenzen, Marce D.; Lord, Jeff; Oppert, Brenda; Kramer, Karl J.; Arakane, Yasuyuki; Oppert, Cris] ARS, Grain Mkt & Prod Res Ctr, USDA, Manhattan, KS 66502 USA. [Posnien, Nico; Schinko, Johannes B.; Simonnet, Franck; Wimmer, Ernst A.; Schuetz, Stefan; Grossmann, Daniela] Univ Gottingen, Johann Friedrich Blumenbach Inst, Dept Dev Biol, D-37077 Gottingen, Germany. [Friedrich, Markus; Bao, Riyue; Yang, Xiaoyun] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. [Grimmelikhuijzen, Cornelis J. P.; Hauser, Frank; Cazzamali, Giuseppe; Williamson, Michael] Univ Copenhagen, Ctr Funct & Comparat Insect Genom, DK-2100 Copenhagen, Denmark. [Hauser, Frank; Cazzamali, Giuseppe; Williamson, Michael] Univ Copenhagen, Dept Cell Biol & Comparat Zool, Inst Biol, DK-2100 Copenhagen, Denmark. [Klingler, Martin; Klingler, Martin; Schmitt, Christian; Schoppmeier, Michael; Trauner, Jochen] Friedrich Alexander Univ Erlangen, Dept Dev Biol, Inst Biol, D-91058 Erlangen, Germany. [Roth, Siegfried; von Levetsow, Cornelia; Lynch, Jeremy A.; da Fonseca, Rodrigo Nunes; Roth, Siegfried] Univ Cologne, Inst Dev Biol, D-50674 Cologne, Germany. [Schroeder, Reinhard; Beermann, Anke; Berns, Nicola; Lutz, Rebekka; Reuter, Rolf; Wittkopp, Nadine] Univ Tubingen, Interfac Inst Cell Biol, D-72076 Tubingen, Germany. [Tautz, Diethard; Savard, Joel; Savard, Joel; Aranda, Manuel; Marques-Souza, Henrique; Van der Zee, Maurijn] Univ Cologne, Dept Genet, D-50674 Cologne, Germany. [Zdobnov, Evgeny M.; Wyder, Stefan; Zdobnov, Evgeny M.; Kriventseva, Evgenia V.] Univ Geneva, Med Sch, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Zdobnov, Evgeny M.; Zdobnov, Evgeny M.] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland. [Zdobnov, Evgeny M.; Waterhouse, Robert M.; Zdobnov, Evgeny M.] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. Childrens Hosp Oakland, Res Inst, BACPAC Resources, Oakland, CA 94609 USA. [Garnes, Jeffrey] MIT, Broad Inst, Cambridge, MA 02142 USA. [Garnes, Jeffrey] Harvard Univ, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Gnirke, Andreas; Margolis, Jon] AgraQuest Inc, Davis, CA 95616 USA. [Park, Yoonseong; Li, Bin] Kansas State Univ, Dept Entomol, Manhattan, KS 66506 USA. [Elsik, Christine G.; Reese, Justin T.] Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA. [Elhaik, Eran; Landan, Giddy; Graur, Dan] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA. [Arensburger, Peter; Atkinson, Peter] Univ Calif, Dept Entomol, Riverside, CA 92521 USA. [Beidler, Jim; Tu, Zhijian] Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA. [Demuth, Jeffery P.] Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA. [Drury, Douglas W.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. [Du, Yu-Zhou; Wang, Jian-Jun] Yangzhou Univ, Dept Plant Protect, Yangzhou 225009, Peoples R China. [Fujiwara, Haruhiko; Osanai, Mizuko] Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Chiba 2778562, Japan. [Maselli, Vincenza] European Sch Mol Med, I-80131 Naples, Italy. Telethon Inst Genet & Med, I-80131 Naples, Italy. [Robertson, Hugh M.; Walden, Kimberly K. O.; Robertson, Hugh M.] Univ Illinois, Dept Entomol, Urbana, IL 61801 USA. [Werner, Doreen; Stanke, Mario; Morgenstern, Burkhard] Univ Gottingen, Dept Bioinformat, Inst Microbiol & Genet, D-37077 Gottingen, Germany. [Solovyev, Victor] Univ London, Dept Comp Sci, Surrey TW20 0EX, England. [Kosarev, Peter] Softberry Inc, Mt Kisco, NY 10549 USA. [Brown, Garth; Chen, Hsiu-Chuan; Ermolaeva, Olga; Hlavina, Wratko; Kapustin, Yuri; Kiryutin, Boris; Kitts, Paul; Maglott, Donna; Pruitt, Kim; Sapojnikov, Victor; Souvorov, Alexandre] Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Mackey, Aaron J.] GlaxoSmithKline Inc, Collegeville, PA 19426 USA. [Kriventseva, Evgenia V.] Univ Geneva, Dept Struct Biol & Bioinformat, Sch Med, CH-1211 Geneva, Switzerland. [Kadowaki, Tatsuhiko] Nagoya Univ, Grad Sch Bioagr Sci, Nagoya, Aichi 4648601, Japan. [Bork, Peer; Raible, Florian] European Mol Biol Lab, D-69117 Heidelberg, Germany. [Bork, Peer] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. [Bonneton, Francois; Laudet, Vincent] Univ Lyon 1, Inst Genom Fonctionnelle Lyon, Equipe Zool Mol, ENS Lyon,CNRS,UMR 5242,INRA,IFR128, F-69364 Lyon 07, France. [Bopp, Daniel] Univ Zurich, Zool Inst, CH-8057 Zurich, Switzerland. [Butts, Thomas; Ferrier, David E. K.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. [Chaumot, Arnaud] CEMAGREF, Lab Ecotoxicol, F-69336 Lyon 09, France. [Jindra, Marek] Inst Entomol ASCR, Ceske Budejovice 37005, Czech Republic. [Lan, Que] Univ Wisconsin, Dept Entomol, Madison, WI 53706 USA. [Lattorff, H. Michael G.] Univ Halle Wittenberg, Inst Biol, D-06099 Halle, Saale, Germany. [Liu, Zhenyi] Washington Univ, Dept Mol Biol & Pharmacol, Sch Med, St Louis, MO 63110 USA. [Vervoort, Michel] Univ Paris 07, Ctr Genet Mol, CNRS UPR 2167, F-91198 Gif Sur Yvette, France. [Jones, Andrew K.; Sattelle, David B.] Univ Oxford, MRC Funct Genet Unit, Dept Physiol Anat & Genet, Oxford OX1 3QX, England. [Ebert, Paul R.] Univ Queensland, Sch Integrat Biol, St Lucia, Qld 4072, Australia. [Ebert, Paul R.] Univ Queensland, Sch Mol & Microbial Sci, St Lucia, Qld 4072, Australia. [Nelson, David] Univ Tennessee, Dept Mol Sci, Memphis, TN 38163 USA. [Nelson, David] Univ Tennessee, Ct Excellence Genom & Bioinformat, Memphis, TN 38163 USA. [Scott, Jeffrey G.] Cornell Univ, Dept Entomol, Ithaca, NY 14853 USA. [Muthukrishnan, Subbaratnam; Kramer, Karl J.; Arakane, Yasuyuki; Zhu, Qingsong; Hogenkamp, David; Dixit, Radhika] Kansas State Univ, Dept Biochem, Manhattan, KS 66506 USA. [Jiang, Haobo; Zou, Zhen; Lu, Zhiqiang; Zhao, Picheng; Sumathipala, Niranji] Oklahoma State Univ, Dept Entomol & Plant Pathol, Stillwater, OK 74078 USA. [Elpidina, Elena; Vinokurov, Konstantin] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119992, Russia. [Evans, Jay] ARS, USDA, Bee Res Lab, Beltsville, MD 20705 USA. [Altincicek, Boran; Vilcinskas, Andreas] Univ Giessen, Inst Phytopathol & Appl Zool, Interdisciplinary Res Ctr, D-35392 Giessen, Germany. [Williams, Michael; Hultmark, Dan] Umea Univ, Umea Ctr Mol Pathogenesis, SE-90187 Umea, Sweden. [Hetru, Charles] CNRS, Inst Biol Molec Cell, F-67084 Strasbourg, France. [Tanaka, Yoshiaki] Natl Inst Agrobiol Sci, Div Insect Sci, Tsukuba, Ibaraki 3058634, Japan. [Predel, Reinhard; Neupert, Susanne] Univ Jena, Inst Gen Zool, D-07743 Jena, Germany. [Schachtner, Joachim] Univ Marburg, Dept Anim Physiol, D-35032 Marburg, Germany. [Verleyen, Peter] Univ Louvain, Dept Anim Physiol & Neurobiol, BE-3000 Louvain, Belgium. [Angeli, Sergio] Inst Forest Zool & Forest Conservat, D-37077 Gottingen, Germany. [Foret, Sylvain; Maleszka, Ryszard] Australian Natl Univ, Visual Sci & ARC Ctr Mol Genet Dev, Res Sch Biol Sci, Canberra, ACT 0200, Australia. RP Richards, S (reprint author), Baylor Coll Med, Human Genome Sequencing Ctr, 1 Baylor Plaza, Houston, TX 77030 USA. RI Zdobnov, Evgeny/K-1133-2012; Marshall, Jeremy/D-1436-2013; Ferrier, David/D-7595-2013; Bork, Peer/F-1813-2013; Marion-Poll, Frederic/D-8882-2011; Z., Q./I-4446-2013; Klingler, Martin/J-8383-2013; Maleszka, Ryszard/A-6078-2008; Entomologiamolecular, Inct/J-8214-2013; Evans, Jay/C-8408-2012; ZHAO, PICHENG/G-3737-2014; Bao, Riyue/G-8765-2014; Maselli, Vincenza/H-4672-2014; Hauser, Frank/M-2952-2014; Liu, Zhenyi/H-5673-2011; Morgenstern, Burkhard/A-7486-2008; Angeli, Sergio/A-7720-2008; Altincicek, Boran/C-1191-2009; Schachtner, Joachim/D-5522-2009; Lattorff, H. Michael/F-6287-2010; Roth, Siegfried/E-8241-2010; Fonseca, Rodrigo/B-2981-2009; Foret, Sylvain/C-7661-2011; Tautz, Diethard/D-4304-2011; Aranda Lastra, Manuel/D-9530-2011; Vinokurov, Konstantin/F-9521-2011; Raible, Florian/G-6019-2011; Posnien, Nico/D-1639-2012; Bucher, Gregor/B-9004-2015; Predel, Reinhard/O-5243-2015; Hultmark, Dan/C-5058-2013; zou, zhen/C-6134-2016; Waterhouse, Robert/A-1858-2010; Jindra, Marek/H-2082-2014; Tautz, Diethard/H-8436-2014; Elsik, Christine/C-4120-2017; Tomoyasu, Yoshinori/D-3061-2017; Park, Yoonseong/J-5861-2013; OI Ferrier, David/0000-0003-3247-6233; Bork, Peer/0000-0002-2627-833X; Marion-Poll, Frederic/0000-0001-6824-0180; Klingler, Martin/0000-0001-8859-1965; Maleszka, Ryszard/0000-0003-1855-555X; Evans, Jay/0000-0002-0036-4651; Bao, Riyue/0000-0002-6105-1704; Maselli, Vincenza/0000-0002-9877-3751; Hauser, Frank/0000-0001-5563-2345; Angeli, Sergio/0000-0002-8463-7476; Altincicek, Boran/0000-0003-2019-452X; Lattorff, H. Michael/0000-0002-8603-6332; Roth, Siegfried/0000-0001-5772-3558; Fonseca, Rodrigo/0000-0003-3063-7806; Aranda Lastra, Manuel/0000-0001-6673-016X; Posnien, Nico/0000-0003-0700-5595; Bucher, Gregor/0000-0002-4615-6401; Hultmark, Dan/0000-0002-6506-5855; zou, zhen/0000-0003-3550-7656; Waterhouse, Robert/0000-0003-4199-9052; Jindra, Marek/0000-0002-2196-9924; Tautz, Diethard/0000-0002-0460-5344; Elsik, Christine/0000-0002-4248-7713; Tomoyasu, Yoshinori/0000-0001-9824-3454; Bonneton, Francois/0000-0002-6500-1931; Nelson, David/0000-0003-0583-5421; Park, Yoonseong/0000-0003-1191-7335; Grimmelikhuijzen, Cornelis/0000-0001-6486-2046; Wyder, Stefan/0000-0002-3412-0292; Landan, Giddy/0000-0002-2502-8750; Solovyev, Victor/0000-0001-8885-493X; chaumot, arnaud/0000-0001-9132-3419 NR 51 TC 564 Z9 592 U1 9 U2 179 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 24 PY 2008 VL 452 IS 7190 BP 949 EP 955 DI 10.1038/nature06784 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291PF UT WOS:000255208600030 ER PT J AU Zhou, ZF Zhu, GS Hariri, AR Enoch, MA Scott, D Sinha, R Virkkunen, M Mash, DC Lipsky, RH Hu, XZ Hodgkinson, CA Xu, K Buzas, B Yuan, QP Shen, PH Ferrell, RE Manuck, SB Brown, SM Hauger, RL Stohler, CS Zubieta, JK Goldman, D AF Zhou, Zhifeng Zhu, Guanshan Hariri, Ahmad R. Enoch, Mary-Anne Scott, David Sinha, Rajita Virkkunen, Matti Mash, Deborah C. Lipsky, Robert H. Hu, Xian-Zhang Hodgkinson, Colin A. Xu, Ke Buzas, Beata Yuan, Qiaoping Shen, Pei-Hong Ferrell, Robert E. Manuck, Stephen B. Brown, Sarah M. Hauger, Richard L. Stohler, Christian S. Zubieta, Jon-Kar Goldman, David TI Genetic variation in human NPY expression affects stress response and emotion SO NATURE LA English DT Article ID NEUROPEPTIDE-Y DISTRIBUTION; HUMAN AMYGDALA; SEROTONIN TRANSPORTER; POLYMORPHISM; BRAIN; GENOTYPE; DISEASE; ANXIETY; PAIN; ASSOCIATION AB Understanding inter- individual differences in stress response requires the explanation of genetic influences at multiple phenotypic levels, including complex behaviours and the metabolic responses of brain regions to emotional stimuli. Neuropeptide Y ( NPY) is anxiolytic(1,2) and its release is induced by stress(3). NPY is abundantly expressed in regions of the limbic system that are implicated in arousal and in the assignment of emotional valences to stimuli and memories(4-6). Here we show that haplotype- driven NPY expression predicts brain responses to emotional and stress challenges and also inversely correlates with trait anxiety. NPY haplotypes predicted levels of NPY messenger RNA in postmortem brain and lymphoblasts, and levels of plasma NPY. Lower haplotype- driven NPY expression predicted higher emotion- induced activation of the amygdala, as well as diminished resiliency as assessed by pain/ stress- induced activations of endogenous opioid neurotransmission in various brain regions. A single nucleotide polymorphism ( SNP rs16147) located in the promoter region alters NPY expression in vitro and seems to account for more than half of the variation in expression in vivo. These convergent findings are consistent with the function of NPY as an anxiolytic peptide and help to explain inter- individual variation in resiliency to stress, a risk factor for many diseases. C1 [Zhou, Zhifeng; Zhu, Guanshan; Enoch, Mary-Anne; Lipsky, Robert H.; Hu, Xian-Zhang; Hodgkinson, Colin A.; Xu, Ke; Buzas, Beata; Yuan, Qiaoping; Shen, Pei-Hong; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Hariri, Ahmad R.; Ferrell, Robert E.; Manuck, Stephen B.; Brown, Sarah M.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA. [Hariri, Ahmad R.; Ferrell, Robert E.; Manuck, Stephen B.; Brown, Sarah M.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. [Hariri, Ahmad R.; Ferrell, Robert E.; Manuck, Stephen B.; Brown, Sarah M.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15261 USA. [Scott, David; Zubieta, Jon-Kar] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. [Scott, David; Zubieta, Jon-Kar] Univ Michigan, Sch Med, Dept Radiol, Ann Arbor, MI 48109 USA. [Sinha, Rajita] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. [Virkkunen, Matti] Univ Helsinki, Dept Psychiat, Helsinki 00014, Finland. [Mash, Deborah C.] Univ Miami, Sch Med, Dept Neurol, Miami, FL 33124 USA. [Hauger, Richard L.] San Diego VA Healthcare Syst, Dept Psychiat, San Diego, CA 92161 USA. [Hauger, Richard L.] Univ Calif San Diego, San Diego, CA 92161 USA. [Stohler, Christian S.] Univ Maryland, Sch Dent, Baltimore, MD 21201 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM davidgoldman@mail.nih.gov RI Hariri, Ahmad/D-5761-2011; Goldman, David/F-9772-2010 OI Lipsky, Robert/0000-0001-7753-1473; Goldman, David/0000-0002-1724-5405 FU Intramural NIH HHS [Z01 AA000301-09, Z99 AA999999]; NHLBI NIH HHS [P01 HL040962, R01 HL065137]; NIAAA NIH HHS [R01 AA013892, R01-AA13892]; NIDA NIH HHS [K02-DA17232, K02 DA017232, P50 DA016556, P50-DA16556, PL1 DA024859, PL1 DA024859-02, R01 DA 016423, R01 DA016423]; NIDCR NIH HHS [R01 DE 15396, R01 DE015396]; NIMH NIH HHS [K01 MH072837, R01 MH074697, R01 MH074697-04A1] NR 35 TC 228 Z9 235 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 24 PY 2008 VL 452 IS 7190 BP 997 EP U8 DI 10.1038/nature06858 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291PF UT WOS:000255208600040 PM 18385673 ER PT J AU Zink, CF Tong, YX Chen, Q Bassett, DS Stein, JL Meyer-Lindenberg, A AF Zink, Caroline F. Tong, Yunxia Chen, Qiang Bassett, Danielle S. Stein, Jason L. Meyer-Lindenberg, Andreas TI Know your place: Neural processing of social hierarchy in humans SO NEURON LA English DT Article ID MEDIAL PREFRONTAL CORTEX; RHESUS MACAQUES; MOTOR AREAS; FMRI; ACTIVATION; DOMINANCE; HEALTH; AGGRESSION AB Social hierarchies guide behavior in many species, including humans, where status also has an enormous impact on motivation and health. However, little is known about the underlying neural representation of social hierarchies in humans. In the present study, we identify dissociable neural responses to perceived social rank using functional magnetic resonance imaging (fMRI) in an interactive, simulated social context. In both stable and unstable social hierarchies, viewing a superior individual differentially engaged perceptual-attentional, saliency, and cognitive systems, notably dorsolateral prefrontal cortex. In the unstable hierarchy setting, additional regions related to emotional processing (amygdala), social cognition (medial prefrontal cortex), and behavioral readiness were recruited. Furthermore, social hierarchical consequences of performance were neurally dissociable and of comparable salience to monetary reward, providing a neural basis for the high motivational value of status. Our results identify neural mechanisms that may mediate the enormous influence of social status on human behavior and health. C1 [Zink, Caroline F.; Tong, Yunxia; Bassett, Danielle S.; Stein, Jason L.; Meyer-Lindenberg, Andreas] NIMH, Unit Syst Neurosci Psychiat, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chen, Qiang; Stein, Jason L.; Meyer-Lindenberg, Andreas] NIMH, Neuroimaging Core Facil, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-68159 Mannheim, Germany. RP Zink, CF (reprint author), NIMH, Unit Syst Neurosci Psychiat, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM zinkc@mail.nih.gov; a.meyer-lindenberg@zi-mannheim.de RI Tong, Yunxia/C-1276-2010; Meyer-Lindenberg, Andreas/H-1076-2011; OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Stein, Jason/0000-0003-4829-0513 FU Intramural NIH HHS [Z99 MH999999] NR 35 TC 195 Z9 199 U1 5 U2 54 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 24 PY 2008 VL 58 IS 2 BP 273 EP 283 DI 10.1016/j.neuron.2008.01.025 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 292YX UT WOS:000255303100014 PM 18439411 ER PT J AU Bardy, GH Lee, KL Mark, DB Poole, JE Toff, WD Tonkin, AM Smith, W Dorian, P Packer, DL White, RD Longstreth, WT Anderson, J Johnson, G Bischoff, E Yallop, JJ McNulty, S Ray, LD Clapp-Channing, NE Rosenberg, Y Schron, EB AF Bardy, Gust H. Lee, Kerry L. Mark, Daniel B. Poole, Jeanne E. Toff, William D. Tonkin, Andrew M. Smith, Warren Dorian, Paul Packer, Douglas L. White, Roger D. Longstreth, W. T., Jr. Anderson, Jill Johnson, George Bischoff, Eric Yallop, Julie J. McNulty, Steven Ray, Linda Davidson Clapp-Channing, Nancy E. Rosenberg, Yves Schron, Eleanor B. CA HAT Investigators TI Home use of automated external defibrillators for sudden cardiac arrest SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GUSTO-I TRIAL; MYOCARDIAL-INFARCTION; CARDIOVERTER-DEFIBRILLATOR; CLINICAL-TRIALS; HEART-DISEASE; SURVIVAL; RESUSCITATION; IMPLANTATION; VICTIMS; RATES AB Background: The most common location of out-of-hospital sudden cardiac arrest is the home, a situation in which emergency medical services are challenged to provide timely care. Consequently, home use of an automated external defibrillator (AED) might offer an opportunity to improve survival for patients at risk. Methods: We randomly assigned 7001 patients with previous anterior-wall myocardial infarction who were not candidates for an implantable cardioverter-defibrillator to receive one of two responses to sudden cardiac arrest occurring at home: either the control response (calling emergency medical services and performing cardiopulmonary resuscitation [CPR]) or the use of an AED, followed by calling emergency medical services and performing CPR. The primary outcome was death from any cause. Results: The median age of the patients was 62 years; 17% were women. The median follow-up was 37.3 months. Overall, 450 patients died: 228 of 3506 patients (6.5%) in the control group and 222 of 3495 patients (6.4%) in the AED group (hazard ratio, 0.97; 95% confidence interval, 0.81 to 1.17; P=0.77). Mortality did not differ significantly in major prespecified subgroups. Only 160 deaths (35.6%) were considered to be from sudden cardiac arrest from tachyarrhythmia. Of these deaths, 117 occurred at home; 58 at-home events were witnessed. AEDs were used in 32 patients. Of these patients, 14 received an appropriate shock, and 4 survived to hospital discharge. There were no documented inappropriate shocks. Conclusions: For survivors of anterior-wall myocardial infarction who were not candidates for implantation of a cardioverter-defibrillator, access to a home AED did not significantly improve overall survival, as compared with reliance on conventional resuscitation methods. C1 [Bardy, Gust H.; Anderson, Jill; Johnson, George; Bischoff, Eric] Seattle Inst Cardiac Res, Seattle, WA 98103 USA. [Poole, Jeanne E.; Longstreth, W. T., Jr.] Univ Washington, Seattle, WA 98195 USA. [Lee, Kerry L.; Mark, Daniel B.; McNulty, Steven; Ray, Linda Davidson; Clapp-Channing, Nancy E.] Duke Univ, Clin Res Inst, Durham, NC USA. [Toff, William D.] Univ Leicester, Leicester, Leics, England. [Tonkin, Andrew M.; Yallop, Julie J.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Smith, Warren; Yallop, Julie J.] Auckland City Hosp, Auckland, New Zealand. [Dorian, Paul] Univ Toronto, Toronto, ON, Canada. [Packer, Douglas L.; White, Roger D.] Mayo Clin, Rochester, MN USA. [Rosenberg, Yves; Schron, Eleanor B.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Bardy, GH (reprint author), Seattle Inst Cardiac Res, 7900 E Green Lake Dr N,302, Seattle, WA 98103 USA. EM gbardy@sicr.org OI Toff, William/0000-0001-5631-4496; Mark, Daniel/0000-0001-6340-8087 FU NCRR NIH HHS [K23 RR018298]; NHLBI NIH HHS [U01 HL067972, U01-HL67972] NR 31 TC 119 Z9 121 U1 0 U2 1 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 APR 24 PY 2008 VL 358 IS 17 BP 1793 EP 1804 DI 10.1056/NEJMoa0801651 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 291PL UT WOS:000255209200005 PM 18381485 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI Please comment, but with civility SO RETROVIROLOGY LA English DT Editorial Material ID RETROVIROLOGY AB Retrovirology provides the opportunity for readers to post comments online for all published articles. These comments are moderated by the journal editors and are often peer reviewed prior to posting. Retrovirology welcomes comments, but asks that they be written civilly. C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 6 TC 0 Z9 0 U1 0 U2 1 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 APR 24 PY 2008 VL 5 AR 35 DI 10.1186/1742-4690-5-35 PG 2 WC Virology SC Virology GA 304ZS UT WOS:000256148200001 PM 18435851 ER PT J AU Gorouhi, F Islami, F Bahrami, H Kamangar, F AF Gorouhi, F. Islami, F. Bahrami, H. Kamangar, F. TI Tumour-necrosis factor-A polymorphisms and gastric cancer risk: a meta-analysis SO BRITISH JOURNAL OF CANCER LA English DT Article DE TNF; gastric cancer; polymorphism; inflammation; genetic ID CYTOKINE GENE POLYMORPHISMS; HELICOBACTER-PYLORI INFECTION; CHRONIC ATROPHIC GASTRITIS; RECEPTOR ANTAGONIST GENE; FACTOR-ALPHA; TNF-A; PROMOTER POLYMORPHISMS; CHINESE POPULATION; CARCINOMA; SUSCEPTIBILITY AB Inflammation is one of the early phases in the development of gastric cancer. Therefore, several studies have examined the association of polymorphisms in tumour-necrosis factor-A gene (TNF-A) with gastric cancer risk. This meta-analysis reviews and summarises published evidence for these associations. Searching several databases yielded 24 independent studies that reported on the associations between TNF-A polymorphisms and gastric cancer risk. We analysed available data for the most commonly investigated polymorphisms: TNF-A -308G > A (23 studies), TNF-A -238G > A (9 studies), and TNF-A -857C > T (5 studies). Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in the random-effects model using the DerSimonian - Laird method. Q-statistic and I-2-statistic were calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects. The overall ORs (95% CIs) for AG and AA genotypes vs GG genotype for TNF-A -308 were 1.09 (0.94 - 1.27) and 1.49 (1.11 - 1.99), respectively. For TNF-A -238, the corresponding ORs (95% CIs) were 1.05 (0.84 - 1.33) and 1.25 (0.30 - 5.26), respectively. The overall ORs (95% CIs) for CT and TT genotypes (vs CC) for TNF-A -857 were 1.06 (0.89 - 1.27) and 1.57 (0.91 - 2.70), respectively. The statistically significant association between TNF- A - 308GG and gastric cancer was limited to western populations. This association showed little heterogeneity (I-2 = 0) and remained consistently strong when analyses were limited to anatomic and histologic subtypes of gastric cancer, or limited to studies in which genotype frequencies were in Hardy - Weinberg equilibrium, or limited to larger studies. These same subgroup analyses did not change results associated with other polymorphisms. In conclusion, TNF-A -308AA genotype was associated with a statistically significant increased risk of gastric cancer, whereas other studied polymorphisms were not. The association between TNF-A -857TT genotype and gastric cancer was near significant, and may become significant if more studies are published. C1 [Kamangar, F.] NIH, Div Canc Epidemiol & Genet, Natl Canc Inst, Bethesda, MD 20892 USA. [Gorouhi, F.] Reading Hosp Med Ctr, Dept Med, W Reading, PA USA. [Islami, F.] Univ Tehran, Digest Dis Res Ctr, Tehran, Iran. [Islami, F.] Int Agcy Res Canc, F-69372 Lyon, France. [Bahrami, H.] Johns Hopkins Univ, Johns Hopkins Sch Med & Publ Hlth, Dept Med, Baltimore, MD USA. [Bahrami, H.] Johns Hopkins Univ, Johns Hopkins Sch Med & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Kamangar, F (reprint author), NIH, Div Canc Epidemiol & Genet, Natl Canc Inst, 6120 Executive Blvd,Room 3034, Bethesda, MD 20892 USA. EM kamangaf@mail.nih.gov RI Kim, Seongman/N-6910-2014 FU Intramural NIH HHS NR 51 TC 57 Z9 58 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD APR 22 PY 2008 VL 98 IS 8 BP 1443 EP 1451 DI 10.1038/sj.bjc.6604277 PG 9 WC Oncology SC Oncology GA 288SU UT WOS:000255006900020 PM 18319718 ER PT J AU Solomon, SD Wittes, J Finn, PV Fowler, R Viner, J Bertagnolli, MM Arber, N Levin, B Meinert, CL Martin, B Pater, JL Goss, PE Lance, P Obara, S Chew, EY Kim, J Arndt, G Hawk, E AF Solomon, Scott D. Wittes, Janet Finn, Peter V. Fowler, Robert Viner, Jaye Bertagnolli, Monica M. Arber, Nadir Levin, Bernard Meinert, Curtis L. Martin, Barbara Pater, Joseph L. Goss, Paul E. Lance, Peter Obara, Stefanie Chew, Emily Y. Kim, Jonghyeon Arndt, Gretchen Hawk, Ernest CA Cross Trial Safety Assessment Grp TI Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials - The cross trial safety analysis SO CIRCULATION LA English DT Article DE drugs; cardiovascular diseases; cyclooxygenase 2 inhibitors ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ACUTE MYOCARDIAL-INFARCTION; CYCLOOXYGENASE-2 INHIBITORS; SELECTIVE INHIBITORS; COLORECTAL ADENOMAS; COX-2; PREVENTION; EVENTS; PREDICTION; DISEASE AB Background-Observational studies and randomized trials have reported increased cardiovascular risk associated with cyclooxygenase-2 inhibitors. Prior placebo-controlled randomized studies had limited ability to assess the relationship of either celecoxib dose or pretreatment cardiovascular status to risk associated with celecoxib. Our aim was to assess the cardiovascular risk associated with celecoxib in 3 dose regimens and to assess the relationship between baseline cardiovascular risk and effect of celecoxib on cardiovascular events. Methods and Results-We performed a patient-level pooled analysis of adjudicated data from 7950 patients in 6 placebo-controlled trials comparing celecoxib with placebo for conditions other than arthritis with a planned follow-up of at least 3 years. Patients were administered celecoxib in 3 dose regimens: 400 mg QD, 200 mg BID, or 400 mg BID. From the pooled data, we calculated a hazard ratio for all dose regimens combined and individual hazard ratios for each dose regimen and examined whether celecoxib-related risk was associated with baseline cardiovascular risk. The primary end point was the combination of cardiovascular death, myocardial infarction, stroke, heart failure, or thromboembolic event. With 16 070 patient-years of follow-up, the hazard ratio for the composite end point combining the tested doses was 1.6 (95% CI, 1.1 to 2.3). The risk, which increased with dose regimen (P=0.0005), was lowest for the 400-mg-QD dose (hazard ratio, 1.1; 95% CI, 0.6 to 2.0), intermediate for the 200-mg-BID dose (hazard ratio, 1.8; 95% CI, 1.1 to 3.1), and highest for the 400-mg-BID dose (hazard ratio, 3.1; 95% CI, 1.5 to 6.1). Patients at highest baseline risk demonstrated disproportionately greater risk of celecoxib-related adverse events (P for interaction=0.034). Conclusions-We observed evidence of differential cardiovascular risk as a function of celecoxib dose regimen and baseline cardiovascular risk. By further clarifying the extent of celecoxib-related cardiovascular risk, these findings may help guide treatment decisions for patients who derive clinical benefit from selective cyclooxygenase-2 inhibition. C1 [Solomon, Scott D.; Finn, Peter V.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Bertagnolli, Monica M.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Wittes, Janet; Fowler, Robert; Arndt, Gretchen] Stat Collaborat Inc, Washington, DC USA. [Viner, Jaye; Hawk, Ernest] NCI, Bethesda, MD 20892 USA. [Levin, Bernard] Univ Texas MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, Houston, TX USA. [Chew, Emily Y.] NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. [Meinert, Curtis L.; Martin, Barbara] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Goss, Paul E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lance, Peter; Obara, Stefanie] Arizona Canc Ctr, Tucson, AZ USA. [Kim, Jonghyeon] EMMES Corp, Rockville, MD USA. [Pater, Joseph L.] Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada. [Arber, Nadir] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. 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 Intramural NIH HHS [Z99 EY999999] NR 30 TC 210 Z9 215 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 22 PY 2008 VL 117 IS 16 BP 2104 EP 2113 DI 10.1161/CIRCULATIONAHA.108.764530 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 291UR UT WOS:000255222900009 PM 18378608 ER PT J AU Luo, SJ Johnson, WE Martenson, J Antunes, A Martelli, P Uphyrkina, O Traylor-Holzer, K Smith, JLD O'Brien, SJ AF Luo, Shu-Jin Johnson, Warren E. Martenson, Janice Antunes, Agostinho Martelli, Paolo Uphyrkina, Olga Traylor-Holzer, Kathy Smith, James L. D. O'Brien, Stephen J. TI Subspecies genetic assignments of worldwide captive tigers increase conservation value of captive populations SO CURRENT BIOLOGY LA English DT Article ID WILD; INFERENCE; MARKERS AB Tigers (Panthera tigris) are disappearing rapidly from the wild, from over 100,000 in the 1900s to as few as 3000 [1, 2]. Javan (P.t. sondaica), Bali (P.L balica), and Caspian (P.t. virgata) subspecies are extinct, whereas the South China tiger (P.t. amoyensis) persists only in zoos [1, 3]. By contrast, captive tigers are flourishing, with 15,000-20,000 individuals worldwide, outnumbering their wild relatives five to seven times [4]. We assessed subspecies genetic ancestry of 105 captive tigers from 14 countries and regions by using Bayesian analysis and diagnostic genetic markers defined by a prior analysis of 134 voucher tigers of significant genetic distinctiveness [5]. We assigned 49 tigers to one of five subspecies (Bengal P.t. tigris, Sumatran P.t. sumatrae, Indochinese P.t. corbetti, Amur P.t. altaica, and Malayan P.t. jacksoni tigers) and determined 52 had admixed subspecies origins. The tested captive tigers retain appreciable genomic diversity unobserved in their wild counterparts, perhaps a consequence of large population size, century-long introduction of new founders, and managed-breeding strategies to retain genetic variability. Assessment of verified subspecies ancestry offers a powerful tool that, if applied to tigers of uncertain background, may considerably increase the number of purebred tigers suitable for conservation management. C1 [Luo, Shu-Jin; Johnson, Warren E.; Martenson, Janice; Antunes, Agostinho; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. [Luo, Shu-Jin; Smith, James L. D.] Univ Minnesota, Dept Fisheries Wildlife & Conservat Biol, St Paul, MN 55108 USA. [Antunes, Agostinho] Univ Porto, Ctr Interdisciplinar Invest Marinha & Ambiental, CIMAR, P-4050123 Oporto, Portugal. [Martelli, Paolo] Vet Dept, Aberdeen, Hong Kong, Peoples R China. [Uphyrkina, Olga] Inst Biol & Soil Sci, Vladivostok 690022, Russia. [Traylor-Holzer, Kathy] IUCN, SSC, Conservat Breeding Specialist Grp, Apple Valley, MN 55124 USA. RP Luo, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM obrien@ncifcrf.gov RI Scientific output, CIIMAR/E-5122-2012; Johnson, Warren/D-4149-2016; OI Scientific output, CIIMAR/0000-0001-6270-2153; Johnson, Warren/0000-0002-5954-186X; Antunes, Agostinho/0000-0002-1328-1732 NR 21 TC 22 Z9 24 U1 10 U2 86 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 APR 22 PY 2008 VL 18 IS 8 BP 592 EP 596 DI 10.1016/j.cub.2008.03.053 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 291FV UT WOS:000255180000026 PM 18424146 ER PT J AU Marincola, FM AF Marincola, Francesco M. TI Preserving a legacy for our patients: The bedside-to-bench award in translational research SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Editorial Material AB The Journal of Translational Medicine is pleased to announce a prize to recognize outstanding contributions in the field of translational medicine. This year, the Bedside-to-Bench Award was provided by an anonymous donor and supported by the Journal of Translational Medicine Editorial Board. Applications should be submitted directly to the Journal of Translational Medicine [ 1]. C1 NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20854 USA. RP Marincola, FM (reprint author), NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20854 USA. EM fmarincola@mail.cc.nih.gov NR 5 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD APR 22 PY 2008 VL 6 AR 20 DI 10.1186/1479-5876-6-20 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 296QL UT WOS:000255560800001 ER PT J AU Cho, J King, JS Qian, X Harwood, AJ Shears, SB AF Cho, Jaiesoon King, Jason S. Qian, Xun Harwood, Adrian J. Shears, Stephen B. TI Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory capacity of the Rapoport-Luebering glycolytic shunt SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 2,3-BPG; erythrocyte; glycolysis ID INOSITOL POLYPHOSPHATE PHOSPHATASE; RED-BLOOD-CELL; ENZYME-KINETIC EQUATIONS; HUMAN ERYTHROCYTE; BISPHOSPHOGLYCERATE MUTASE; ACID-PHOSPHATASE; IN-VIVO; DICTYOSTELIUM-DISCOIDEUM; 2,3-DIPHOSPHOGLYCERATE; METABOLISM AB The Rapoport-Luebering glycolytic bypass comprises evolutionarily conserved reactions that generate and dephosphorylate 2,3-bisphosphoglycerate (2,3-BPG). For >30 years, these reactions have been considered the responsibility of a single enzyme, the 2,3-BPG synthase/2-phosphatase (BPGM). Here, we show that Dictyosteiium, birds, and mammals contain an additional 2,3-BPG phosphatase that, unlike BPGM, removes the 3-phosphate. This discovery reveals that the glycolytic pathway can bypass the formation of 3-phosphoglycerate, which is a precursor for serine biosynthesis and an activator of AMP-activated protein kinase. Our 2,3-BPG phosphatase activity is encoded by the previously identified gene for multiple inositol polyphosphate phosphatase (MIPP11), which we now show to have dual substrate specificity. By genetically manipulating Mlippl expression in Dictyostelium, we demonstrated that this enzyme provides physiologically relevant regulation of cellular 2,3-BPG content. Mammalian erythrocytes possess the highest content of 2,3-BPG, which controls oxygen binding to hemoglobin. We determined that total MIPP11 activity in erythrocytes at 37 degrees C is 0.6 mmol 2,3-BPG hydrolyzed per liter of cells per h, matching previously published estimates of the phosphatase activity of BPGM. MIPP11 is active at 4 degrees C, revealing a clinically significant contribution to 2,3-BPG loss during the storage of erythrocytes for transfusion. Hydrolysis of 2,3-BPG by human MIPP11 is sensitive to physiologic alkalosis; activity decreases 50% when pH rises from 7.0 to 7.4. This phenomenon provides a homeostatic mechanism for elevating 2,3-BPG levels, thereby enhancing oxygen release to tissues. our data indicate greater biological significance of the Rapoport-Luebering shunt than previously considered. C1 [Cho, Jaiesoon; Qian, Xun; Shears, Stephen B.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Social Serv, Res Triangle Pk, NC 27709 USA. [King, Jason S.; Harwood, Adrian J.] Cardiff Univ, Cardiff Sch Biosci, Cardiff CF10 3US, S Glam, Wales. RP Shears, SB (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Social Serv, PO Box 12233, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov RI Harwood, Adrian/A-4350-2010; King, Jason/D-6228-2011; OI King, Jason/0000-0003-0596-4506; Harwood, Adrian/0000-0003-3124-5169 FU Biotechnology and Biological Sciences Research Council; Intramural NIH HHS; Wellcome Trust NR 41 TC 18 Z9 21 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 APR 22 PY 2008 VL 105 IS 16 BP 5998 EP 6003 DI 10.1073/pnas.0710980105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 293SW UT WOS:000255356000011 PM 18413611 ER PT J AU Matsumoto, M Straub, RE Marenco, S Nicodemus, KK Matsumoto, SI Fujikawa, A Miyoshi, S Shobo, M Takahashi, S Yarimizu, J Yuri, M Hiramoto, M Morita, S Yokota, H Sasayama, T Terai, K Yoshino, M Miyake, A Callicott, JH Egan, MF Meyer-Lindenberg, A Kempf, L Honea, R Vakkalanka, RK Takasaki, J Kamohara, M Soga, T Hiyama, H Ishii, H Matsuo, A Nishimura, S Matsuoka, N Kobori, M Matsushime, H Katoh, M Furuichi, K Weinberger, DR AF Matsumoto, Mitsuyuki Straub, Richard E. Marenco, Stefano Nicodemus, Kristin K. Matsumoto, Shun-ichiro Fujikawa, Akihiko Miyoshi, Sosuke Shobo, Miwako Takahashi, Shinji Yarimizu, Junko Yuri, Masatoshi Hiramoto, Masashi Morita, Shuji Yokota, Hiroyuki Sasayama, Takeshi Terai, Kazuhiro Yoshino, Masayasu Miyake, Akira Callicott, Joseph H. Egan, Michael F. Meyer-Lindenberg, Andreas Kempf, Lucas Honea, Robyn Vakkalanka, Radha Krishna Takasaki, Jun Kamohara, Masazumi Soga, Takatoshi Hiyama, Hideki Ishii, Hiroyuki Matsuo, Ayako Nishimura, Shintaro Matsuoka, Nobuya Kobori, Masato Matsushime, Hitoshi Katoh, Masao Furuichi, Kiyoshi Weinberger, Daniel R. TI The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene manipulation; memory; SNPs ID LHERMITTE-DUCLOS-DISEASE; KINASE-B-GAMMA; SUSCEPTIBILITY LOCUS; ADULT HUMAN; SOMA SIZE; MOUSE; MICE; DISORDER; RISK; ABNORMALITIES AB The G protein-coupled receptor (GPCR) family is highly diversified and involved in many forms of information processing. SREB2 (GPR85) is the most conserved GPCR throughout vertebrate evolution and is expressed abundantly in brain structures exhibiting high levels of plasticity, e.g., the hippocampal dentate gyrus. Here, we show that SREB2 is involved in determining brain size, modulating diverse behaviors, and potentially in vulnerability to schizophrenia. Mild overexpression of SREB2 caused significant brain weight reduction and ventricular enlargement in transgenic (Tg) mice as well as behavioral abnormalities mirroring psychiatric disorders, e.g., decreased social interaction, abnormal sensorimotor gating, and impaired memory. SREB2 KO mice showed a reciprocal phenotype, a significant increase in brain weight accompanying a trend toward enhanced memory without apparent other behavioral abnormalities. In both Tg and KO mice, no gross malformation of brain structures was observed. Because of phenotypic overlap between SREB2 Tg mice and schizophrenia, we sought a possible link between the two. Minor alleles of two SREB2 SNPs, located in intron 2 and in the 3' UTR, were overtransmitted to schizophrenia patients in a family-based sample and showed an allele load association with reduced hippocampal gray matter volume in patients. Our data implicate SREB2 as a potential risk factor for psychiatric disorders and its pathway as a target for psychiatric therapy. C1 [Matsumoto, Mitsuyuki; Matsumoto, Shun-ichiro; Fujikawa, Akihiko; Miyoshi, Sosuke; Shobo, Miwako; Takahashi, Shinji; Yarimizu, Junko; Yuri, Masatoshi; Hiramoto, Masashi; Morita, Shuji; Yokota, Hiroyuki; Sasayama, Takeshi; Terai, Kazuhiro; Yoshino, Masayasu; Miyake, Akira; Takasaki, Jun; Kamohara, Masazumi; Soga, Takatoshi; Hiyama, Hideki; Ishii, Hiroyuki; Matsuo, Ayako; Nishimura, Shintaro; Matsuoka, Nobuya; Matsushime, Hitoshi; Katoh, Masao; Furuichi, Kiyoshi] Astellas Pharma Inc, Drug Discovery Res, Neurosci Pharmacol Res Labs, Tsukuba, Ibaraki 3058585, Japan. [Straub, Richard E.; Marenco, Stefano; Nicodemus, Kristin K.; Callicott, Joseph H.; Egan, Michael F.; Meyer-Lindenberg, Andreas; Kempf, Lucas; Honea, Robyn; Vakkalanka, Radha Krishna; Weinberger, Daniel R.] NIMH, NIH, Intramural Res Program, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. RP Matsumoto, M (reprint author), Astellas Pharma Inc, Drug Discovery Res, Neurosci Pharmacol Res Labs, 21 Miyukigaoka, Tsukuba, Ibaraki 3058585, Japan. EM mitsuyuki.matsumoto@jp.astellas.com RI Matsumoto, Mitsuyuki/G-3207-2012; Marenco, Stefano/A-2409-2008; Callicott, Joseph/C-9102-2009; Meyer-Lindenberg, Andreas/H-1076-2011 OI Matsumoto, Mitsuyuki/0000-0002-1172-2354; Marenco, Stefano/0000-0002-2488-2365; Callicott, Joseph/0000-0003-1298-3334; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 34 TC 31 Z9 31 U1 0 U2 3 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 APR 22 PY 2008 VL 105 IS 16 BP 6133 EP 6138 DI 10.1073/pnas.0710717105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 293SW UT WOS:000255356000034 PM 18413613 ER PT J AU Manoussaki, D Chadwick, RS Ketten, DR Arruda, J Dimitriadis, EK O'Malley, JT AF Manoussaki, Daphne Chadwick, Richard S. Ketten, Darlene R. Arruda, Julie Dimitriadis, Emilios K. O'Malley, Jen T. TI The influence of cochlear shape on low-frequency hearing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE inner ear; function; mammalian evolution; spiral ID MONGOLIAN GERBIL; SENSITIVITY; RANGE; RAT; THRESHOLDS; ABSOLUTE; COILING; MAMMALS; MICE AB The conventional theory about the snail shell shape of the mammalian cochlea is that it evolved essentially and perhaps solely to conserve space inside the skull. Recently, a theory proposed that the spiral's graded curvature enhances the cochlea's mechanical response to low frequencies. This article provides a multispecies analysis of cochlear shape to test this theory and demonstrates that the ratio of the radii of curvature from the outermost and innermost turns of the cochlear spiral is a significant cochlear feature that correlates strongly with low-frequency hearing limits. The ratio, which is a measure of curvature gradient, is a reflection of the ability of cochlear curvature to focus acoustic energy at the outer wall of the cochlear canal as the wave propagates toward the apex of the cochlea. C1 [Chadwick, Richard S.; Ketten, Darlene R.] Natl Inst Deafness & Other Commun Disorders, NIH, Auditory Mech Sect, Bethesda, MD 20892 USA. [Dimitriadis, Emilios K.] Natl Inst Biomed Imaging & Bioengn, NIH, Lab Bioengn & Phys Sci, Bethesda, MD 20892 USA. [Manoussaki, Daphne] Vanderbilt Univ, Dept Math, Nashville, TN 37240 USA. [Manoussaki, Daphne] Tech Univ Crete, Dept Sci, Hania 73100, Greece. [Ketten, Darlene R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Ketten, Darlene R.; Arruda, Julie] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. [Arruda, Julie; O'Malley, Jen T.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chadwick, RS (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Auditory Mech Sect, Bethesda, MD 20892 USA. EM chadwick@helix.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [Z01 DC000033] NR 40 TC 52 Z9 53 U1 4 U2 18 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 APR 22 PY 2008 VL 105 IS 16 BP 6162 EP 6166 DI 10.1073/pnas.0710037105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 293SW UT WOS:000255356000039 PM 18413615 ER PT J AU Ozarslan, E Basser, PJ AF Oezarslan, Evren Basser, Peter J. TI Microscopic anisotropy revealed by NMR double pulsed field gradient experiments with arbitrary timing parameters SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID LYOTROPIC LIQUID-CRYSTAL; SPIN-ECHO ANALYSIS; RESTRICTED DIFFUSION; SELF-DIFFUSION; WAVE-FORMS; MR SIGNAL; TISSUE; SPECTROSCOPY; RESOLUTION; EXCHANGE AB We consider a general double pulsed field gradient experiment with arbitrary experimental parameters and calculate an exact expression for the NMR signal attenuation from restricted geometries, which is valid at long wavelengths, i.e., when the product of the gyromagnetic ratio of the spins, the pulsed gradients' duration, and their magnitude is small compared to the reciprocal of the pore size. It is possible to observe microscopic anisotropy within the pore space induced by the boundaries of the pore, which can be used to differentiate restricted from free or multicompartmental diffusion and to estimate a characteristic pore dimension in the former case. Explicit solutions for diffusion taking place between parallel plates as well as in cylindrical and spherical pores are provided. In coherently packed cylindrical pores, it is possible to measure simultaneously the cylinders' orientation and diameter using small gradient strengths. The presence of orientational heterogeneity of cylinders is addressed, and a scheme for differentiating microscopic from ensemble anisotropy is proposed. C1 [Oezarslan, Evren; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. RP Ozarslan, E (reprint author), NICHD, Sect Tissue Biophys & Biomimet, NIH, 13 South Dr, Bethesda, MD 20892 USA. EM evren@helix.nih.gov RI Basser, Peter/H-5477-2011; Ozarslan, Evren/B-4858-2013 OI Ozarslan, Evren/0000-0003-0859-1311 FU Intramural NIH HHS NR 32 TC 58 Z9 58 U1 2 U2 8 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 APR 21 PY 2008 VL 128 IS 15 AR 154511 DI 10.1063/1.2905765 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 291WW UT WOS:000255228900058 PM 18433239 ER PT J AU Li, ND Wang, LM Cui, LH Zhang, L Dai, SZ Li, HY Chen, X Zhu, LN Hejtmancik, JF Zhao, KX AF Li, Ningdong Wang, Liming Cui, Lihong Zhang, Li Dai, Suzhen Li, Hongyan Chen, Xia Zhu, Lina Hejtmancik, James F. Zhao, Kanxing TI Five novel mutations of the FRMD7 gene in Chinese families with X-linked infantile nystagmus SO MOLECULAR VISION LA English DT Article ID CONGENITAL MOTOR NYSTAGMUS; MAPS; 6P12 AB Purpose: Infantile nystagmus (IN) is an inherited disorder characterized by bilateral ocular oscillatory movements. Recently, mutations in FRMD7 were found to be responsible for X-linked idiopathic infantile nystagmus. We investigated the role of the FRMD7 gene mutations in seven Chinese families with infantile nystagmus. Methods: Linkage analysis was performed with fluorescently labeled microsatellite markers, DXS1001 and DXS1047. Analysis of FRMD7 gene mutations was performed by direct sequence to the whole coding regions and exon-intron boundaries of FRMD7 gene in all affected members in seven families with IN. Results: Five novel FRMD7 gene mutations, 70 G > T(p.G24W) in exon 2, c. 689-690delAG (p.Ser232del) in exon8, c. 782G > A (p.R260Q) and c. 812G > T (p.C271F) in exon 9, and c. 910C > T (R303X) in exon 10, were identified in five of seven Chinese families with X-linked infantile nystagmus. But we didn't detect the FRMD7 gene mutation in one of seven families, although a positive LOD score of 2.42 (theta max=0.1) was obtained at DXS1047. We also found the same mutation, which is c. 782G > A (p.R260Q), occurred in two different families. Conclusions: This is first report that five kinds of FRMD7 gene mutation types occurred in Chinese families with IN, which further support that FRMD7 gene mutations are the underlying pathogenesis of the molecular mechanism for infantile nystagmus. C1 [Cui, Lihong; Zhao, Kanxing] Tianjin Med Univ, Tianjin 300070, Peoples R China. [Li, Ningdong; Wang, Liming; Chen, Xia; Zhu, Lina; Zhao, Kanxing] Tianjin Eye Hosp, Tianjin Eye Inst, Tianjin, Peoples R China. [Zhang, Li; Dai, Suzhen] HeNan Eye Inst, Zhengzhou, HeNan Province, Peoples R China. [Hejtmancik, James F.] NEI, Natl Inst Hlth, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. RP Zhao, KX (reprint author), Tianjin Med Univ, Tianjin 300070, Peoples R China. EM zkx@tijmu.edu.cn NR 12 TC 16 Z9 22 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD APR 21 PY 2008 VL 14 IS 87-89 BP 733 EP 738 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 320VR UT WOS:000257263700001 PM 18431453 ER PT J AU Donohue, SR Halldin, C Pike, VW AF Donohue, Sean R. Halldin, Christer Pike, Victor W. TI A facile and regioselective synthesis of rimonabant through an enamine-directed 1,3-dipolar cycloaddition SO TETRAHEDRON LETTERS LA English DT Article DE CB; receptor; 1,5-diarylpyrazole; rimonabant; 1,3-dipolar cycloaddition ID CANNABINOID RECEPTOR AB Rimonabant is a high-potency cannabinoid type-1 (CB(1)) receptor inverse agonist that has recently been approved in the European Union as a treatment for obesity. Current methods of synthesis require several steps that have long reaction times and/or lack regio-selectivity. Here we present a novel, regioselective synthesis of rimonabant though an enamine-directed 1,3-dipolar cycloaddition. In addition, we present a new and more reactive hydrazonoyl halide for the generation of the requisite nitrile imine dipole. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Donohue, Sean R.; Pike, Victor W.] NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Donohue, Sean R.; Halldin, Christer] Karolinska Hosp, Dept Clin Neurosci, Karolinska Inst, S-17176 Stockholm, Sweden. RP Donohue, SR (reprint author), NIMH, NIH, Mol Imaging Branch, Bldg 10,Rm B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA. EM donohues@intra.nimh.nih.gov NR 13 TC 36 Z9 36 U1 0 U2 5 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 APR 21 PY 2008 VL 49 IS 17 BP 2789 EP 2791 DI 10.1016/j.tetlet.2008.02,132 PG 3 WC Chemistry, Organic SC Chemistry GA 292MO UT WOS:000255270500028 ER PT J AU Gargas, ML Collins, B Fennell, TR Gaudette, NF Sweeney, LM AF Gargas, Michael L. Collins, Brad Fennell, Timothy R. Gaudette, Norman F., Jr. Sweeney, Lisa M. TI Disposition of styrene-acrylonitrile (SAN) trimer in female rats: Single dose intravenous and gavage studies SO TOXICOLOGY LETTERS LA English DT Article DE styrene-acrylonitrile trimer (SAN Trimer); pharmacokinctics; perinatal ID TOMS-RIVER; NEW-JERSEY AB Styrene-acrylonitrile trimer (SAN Trimer), a mixture of six isomers (four isomers of 4-cyano-1,2,3,4-tetrahydro-alpha-methyl-1-naphthaleneacetonitrile [THAN] and two isomers of 4-cyano- 1,2,3,4-tetrahydro-1-naphthaleneproprionitrile [THNP]), is a by-product of a specific production process of styrene-acrylonitrile polymer. Disposition studies in female rats were conducted to evaluate the pharmacokinetic behavior of [H-3]SAN Trimer following a single intravenous administration (26 mg/kg) to nonpregnant rats; a single gavage administration (nominal doses of 25 mg/kg, 75 mg/kg, or 200 mg/kg in corn oil) to nonpregnant rats; and a single gavage administration (nominal dose of 200 mg/kg in corn oil) to pregnant and lactating rats. SAN Trimer was rapidly eliminated from blood (T-1/2 similar to 1 h) following a single intravenous dose and following single oral doses (T-1/2 similar to 3-4 h). SAN Trimer was also rapidly excreted in the urine and feces following single oral doses, while total radioactivity was cleared more slowly. In pregnant rats, the concentrations of both radioactivity and SAN Trimer 2 It after dosing were highest in the blood, followed by the placenta, with the lowest levels in the fetus. In lactating rats, the concentrations of both radioactivity and SAN Trimer were higher in milk than in maternal blood. Total radioactivity and SAN Trimer blood concentrations in nonpregnant, pregnant, and lactating rats were both higher in lactating rats compared to nonpregnant and pregnant rats. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Gargas, Michael L.; Sweeney, Lisa M.] Sapphire Grp Inc, Dayton, OH 45431 USA. [Collins, Brad] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Fennell, Timothy R.; Gaudette, Norman F., Jr.] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Gargas, ML (reprint author), Sapphire Grp Inc, 2661 Commons Blvd,2nd Floor, Dayton, OH 45431 USA. EM MLG@TheSapphireGroup.com RI Fennell, Tim/D-9936-2013; Sweeney, Lisa/K-5114-2012 OI Sweeney, Lisa/0000-0002-4672-7358 NR 12 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD APR 21 PY 2008 VL 178 IS 1 BP 1 EP 8 DI 10.1016/j.toxlet.2008.01.016 PG 8 WC Toxicology SC Toxicology GA 300MW UT WOS:000255828900001 PM 18384980 ER PT J AU Goss, PE Ingle, JN Pater, JL Martino, S Robert, NJ Muss, HB Piccart, MJ Castiglione, M Shepherd, LE Pritchard, KI Livingston, RB Davidson, NE Norton, L Perez, EA Abrams, JS Cameron, DA Palmer, MJ Tu, DS AF Goss, Paul E. Ingle, James N. Pater, Joseph L. Martino, Silvana Robert, Nicholas J. Muss, Hyman B. Piccart, Martine J. Castiglione, Monica Shepherd, Lois E. Pritchard, Kathleen I. Livingston, Robert B. Davidson, Nancy E. Norton, Larry Perez, Edith A. Abrams, Jeffrey S. Cameron, David A. Palmer, Michael J. Tu, Dongsheng TI Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ONCOLOGY-TECHNOLOGY-ASSESSMENT; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; RANDOMIZED-TRIAL; AMERICAN-SOCIETY; UPDATED FINDINGS; THERAPY; SURVIVAL; ESTROGEN AB Purpose The National Cancer Institute of Canada Clinical Trials Group MA. 17 trial examined the efficacy of letrozole (LET) started within 3 months of 5 years of adjuvant tamoxifen in postmenopausal hormone receptor-positive early-stage breast cancer. When the trial was unblinded, patients who received placebo (PLAC) were offered LET. Patients and Methods This cohort analysis describes the outcomes of women assigned PLAC at the initial random assignment after unblinding. Efficacy outcomes of women who chose LET (PLAC-LET group) were compared with those who did not (PLAC-PLAC group) by the hazard ratios and by P values calculated from Cox models that adjusted for imbalances between the groups. Toxicity analyses included only events that occurred after unblinding. Results There were 1,579 women in the PLAC-LET group (median time from tamoxifen, 2.8 years) and 804 in the PLAC-PLAC group. Patients in the PLAC-LET group were younger; had a better performance status; and were more likely to have had node-positive disease, axillary dissection, and adjuvant chemotherapy than those in the PLAC-PLAC group. At a median follow-up of 5.3 years, disease-free survival (DFS; adjusted hazard ratio [ HR], 0.37; 95% CI, 0.23 to 0.61; P <.0001) and distant DFS (HR, 0.39; 95% CI, 0.20 to 0.74; P =.004) were superior in the PLAC-LET group. More self-reported new diagnoses of osteoporosis and significantly more clinical fractures occurred in the women who took LET (5.2% v 3.1%, P =.02). Conclusion Interpretation of this cohort analysis suggests that LET improves DFS and distant DFS even when there has been a substantial period of time since the discontinuation of prior adjuvant tamoxifen. C1 [Goss, Paul E.; Ingle, James N.; Pater, Joseph L.; Martino, Silvana; Robert, Nicholas J.; Muss, Hyman B.; Piccart, Martine J.; Castiglione, Monica; Shepherd, Lois E.; Pritchard, Kathleen I.; Livingston, Robert B.; Davidson, Nancy E.; Norton, Larry; Perez, Edith A.; Abrams, Jeffrey S.; Cameron, David A.; Palmer, Michael J.; Tu, Dongsheng] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Angeles Clin, Los Angeles, CA USA. Res Inst, Los Angeles, CA USA. Inova Fairfax Hosp, Falls Church, VA USA. Univ Vermont, Burlington, VT USA. Inst Jules Bordet, B-1000 Brussels, Belgium. Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. Natl Canc Inst, Clin Trials Grp, Kingston, ON, Canada. Univ Toronto, Toronto Sunnybrook Odette Canc Ctr, Toronto, ON M5S 1A1, Canada. Univ Washington, Seattle, WA 98195 USA. Sidney Kimmel Copmrehens Canc Ctr, Baltimore, MD USA. NCI, Canc Therapy Evaluat Program, Clin Invest Branch, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Jacksonville, FL 32224 USA. Western Gen Hosp, Edinburgh Breast Unit, Edinburgh EH4 2XU, Midlothian, Scotland. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House,LHR-302, Boston, MA 02114 USA. EM pgoss@partners.org OI Norton, Larry/0000-0003-3701-9250 FU NCI NIH HHS [CA38926, CA21115, CA25224, CA31946, CA32102] NR 18 TC 116 Z9 123 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2008 VL 26 IS 12 BP 1948 EP 1955 DI 10.1200/JCO.2007.11.6798 PG 8 WC Oncology SC Oncology GA 289KZ UT WOS:000255054700010 PM 18332475 ER PT J AU Dzutsev, AK Belyakov, IA Isakov, DV Gagnon, SJ Margulies, DH Berzofsky, JA AF Dzutsev, Amiran K. Belyakov, Igor A. Isakov, Dmitry V. Gagnon, Susan J. Margulies, David H. Berzofsky, Jay A. TI Estimation of low frequency antigen-presenting cells with a novel RELISPOT assay SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE antigen-presenting cell; T-cell line; ELISPOT; RELISPOT; dendritic cell; migration; vaccinia virus ID CD8(+) T-CELLS; RECOMBINANT VACCINIA VIRUS; IMMUNOSPOT ELISPOT ASSAY; DENDRITIC CELLS; PROTECTIVE IMMUNITY; IFN-GAMMA; PEPTIDE; IMMUNIZATION; COMPLEXES; RECEPTOR AB Adequate presentation of self and foreign antigens is a key factor for efficient T-cell immunosurveillance against pathogens and tumors. Cells presenting foreign antigens usually comprise a rare population and are difficult to detect even at the peak of infection. Here we demonstrate a CD8(+) T-cell-based approach that allows detection of specific antigen-presenting cells (APC) at a frequency of less than 0.0005%. When T cells are in excess, they form rosettes with rare APCs, which appear as single spots in an IFN-gamma ELISPOT assay. Using this RELISPOT (Rosette ELISPOT) method we demonstrate the dynamic interplay between CD8 T cells and professional and non-professional APCs following virus challenge. Published by Elsevier B.V. C1 [Dzutsev, Amiran K.; Belyakov, Igor A.; Isakov, Dmitry V.; Gagnon, Susan J.; Berzofsky, Jay A.] NCI, Ctr Canc Res, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Margulies, David H.] NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Ctr Canc Res, Vaccine Branch, NIH, Bldg 10,Rm 6B-04,MSC 1578, Bethesda, MD 20892 USA. EM berzofsk@helix.nih.gov RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU Intramural NIH HHS [Z99 CA999999] NR 26 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR 20 PY 2008 VL 333 IS 1-2 BP 71 EP 78 DI 10.1016/j.jim.2008.01.008 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 299CX UT WOS:000255734500007 PM 18294650 ER PT J AU Ehrenfeld, E Glass, RI Agol, VI Chumakov, K Dowdle, W John, TJ Katz, SL Miller, M Breman, JG Modlin, J Wright, P AF Ehrenfeld, Ellie Glass, Roger I. Agol, Vadim I. Chumakov, Konstantin Dowdle, Walter John, T. Jacob Katz, Samuel L. Miller, Mark Breman, Joel G. Modlin, John Wright, Peter TI Immunisation against poliomyelitis: moving forward SO LANCET LA English DT Editorial Material ID VACCINE-DERIVED POLIOVIRUSES; POLIO ERADICATION; EFFICACY C1 [Glass, Roger I.; Miller, Mark; Breman, Joel G.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Ehrenfeld, Ellie] NIAID, NIH, Bethesda, MD 20892 USA. [Agol, Vadim I.] Inst Poliomyelitis & Viral Encephalitides, Moscow, Russia. [Chumakov, Konstantin] US FDA, PHHS, Rockville, MD 20857 USA. [Dowdle, Walter] Task Force Child Survival & Dev, Atlanta, GA USA. [John, T. Jacob] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Katz, Samuel L.] Duke Univ, Sch Med, Durham, NC USA. [Modlin, John; Wright, Peter] Dartmouth Med Sch, Hanover, NH USA. [Wright, Peter] Vanderbilt Univ Sch Med, Nashville, TN USA. RP Glass, RI (reprint author), NIH, Fogarty Int Ctr, 31 Ctr Dr,MSC 2220, Bethesda, MD 20892 USA. EM glassr@mail.nih.gov RI Agol, Vadim/E-1941-2013 NR 20 TC 17 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR 19 PY 2008 VL 371 IS 9621 BP 1385 EP 1387 DI 10.1016/S0140-6736(08)60597-8 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 291PE UT WOS:000255208500029 PM 18424327 ER PT J AU Inoue, K Negishi, M AF Inoue, Kaoru Negishi, Masahiko TI Nuclear receptor CAR requires early growth response 1 to activate the human cytochrome P4502B6 gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONSTITUTIVE ANDROSTANE RECEPTOR; PREGNANE-X-RECEPTOR; SYNERGISTIC ACTIVATION; FACTOR 4-ALPHA; TARGET GENES; HEPG2 CELLS; CROSS-TALK; P450 GENE; EXPRESSION; FACTOR-4-ALPHA AB The nuclear receptor CAR (constitutive active/androstane receptor) is a drug-sensing transcription factor, regulating the hepatic genes that encode various drug-metabolizing enzymes. We have now characterized the novel regulatory mechanism by which the signal molecule EGR1 (early growth response 1) determines CAR-mediated activation of the human CYP2B6 (cytochrome P450 2B6) gene. The CYP2B6 enzyme metabolizes commonly used therapeutics and also activates pro-drugs. The CAR directly binds to the distal enhancer element of the CYP2B6 promoter, which is essential in converging to its drug-sensing function onto promoter activity. However, this binding alone is not sufficient to activate the CYP2B6 promoter; the promoter requires EGR1 to enable CAR to activate the CYP2B6 promoter. Upon stimulation by protein kinase C, EGR1 directly binds to the proximal promoter and coordinates the nearby HNF4 alpha (hepatocyte-enriched nuclear factor 4 alpha) with CAR at the distal enhancer element to activate the promoter. Thus, synergy of drug activation and the stimulation of cellular signal are necessary for CAR to activate the CYP2B6 gene. C1 [Inoue, Kaoru; Negishi, Masahiko] NIEHS, NIH, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU Intramural NIH HHS NR 30 TC 21 Z9 21 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 APR 18 PY 2008 VL 283 IS 16 BP 10425 EP 10432 DI 10.1074/jbc.M800729200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 287CQ UT WOS:000254894700023 PM 18303024 ER PT J AU Cooper, SK Pandhare, J Donald, SP Phang, JM AF Cooper, Sandra K. Pandhare, Jui Donald, Steven P. Phang, James M. TI Novel function for hydroxyproline oxidase in apoptosis through generation of reactive oxygen species SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOXORUBICIN-INDUCED APOPTOSIS; PROLINE-OXIDASE; CELL-DEATH; ENZYMATIC SYNTHESIS; DNA-DAMAGE; TUMOR-CELL; METABOLISM; DELTA-1-PYRROLINE-3-HYDROXY-5-CARBOXYLATE; EXPRESSION; PATHWAYS AB Proline and hydroxyproline are metabolized by distinct pathways. Proline is important for protein synthesis, as a source of glutamate, arginine, and tricarboxylic acid cycle intermediates, and for participating in a metabolic cycle that shuttles redox equivalents between mitochondria and cytosol. Hydroxyproline, in contrast, is not reutilized for protein synthesis. The first steps in the degradation of proline and hydroxyproline are catalyzed by proline oxidase (POX) and hydroxyproline oxidase (OH-POX), respectively. Because it is well documented that POX is induced by p53 and plays a role in apoptosis, we considered whether OH-POX also participates in the response to cytotoxic stress. In LoVo and RKO cells, which respond to adriamycin with a p53-mediated induction of POX and generation of reactive oxygen species, we found that adriamycin also induced OH-POX gene expression and markedly increased OH-POX catalytic activity, and this increase in activity was not observed in the cell lines HT29 and HCT15, which do not have a functional p53. We also observed an increase in reactive oxygen species generation and activation of caspase-9 with adriamycin in a hydroxyproline-dependent manner. Therefore, we hypothesize that OH-POX plays a role analogous to POX in growth regulation, ROS generation, and activation of the apoptotic cascade. C1 [Pandhare, Jui; Donald, Steven P.; Phang, James M.] Natl Inst Hlth, Comparat Carcinogenesis Lab, NCI, CCR, Ft Detrick, MD 21702 USA. [Cooper, Sandra K.] NCI, Basic Res Program, SAIC Frederick Inc, Natl Inst Hlth, Ft Detrick, MD 21702 USA. RP Phang, JM (reprint author), Natl Inst Hlth, Comparat Carcinogenesis Lab, NCI, CCR, Bldg 538 Rm 144, Ft Detrick, MD 21702 USA. EM phang@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 31 TC 17 Z9 17 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 APR 18 PY 2008 VL 283 IS 16 BP 10485 EP 10492 DI 10.1074/jbc.M702181200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 287CQ UT WOS:000254894700030 PM 18287100 ER PT J AU Choi, SH Czifra, G Kedei, N Lewin, NE Lazar, J Pu, YM Marquez, VE Blumberg, PM AF Choi, Sung Hee Czifra, Gabriella Kedei, Noemi Lewin, Nancy E. Lazar, Jozsef Pu, Yongmei Marquez, Victor E. Blumberg, Peter M. TI Characterization of the interaction of phorbol esters with the C1 domain of MRCK (myotonic dystrophy kinase-related Cdc42 binding kinase) alpha/beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; DIACYLGLYCEROL KINASES; PKC-ALPHA; ACTIVATION; RECEPTORS; MECHANISM; EFFECTORS; CALCIUM; SIGNALS; DELTA AB C1 domains mediate the recognition and subsequent signaling response to diacylglycerol and phorbol esters by protein kinase C (PKC) and by several other families of signal-transducing proteins such as the chimerins or RasGRP. MRCK(myotonic dystrophy kinase-related Cdc42 binding kinase), a member of the dystrophia myotonica protein kinase family that functions downstream of Cdc42, contains a C1 domain with substantial homology to that of the diacylglycerol/phorbol ester-responsive C1 domains and has been reported to bind phorbol ester. We have characterized here the interaction of the C1 domains of the two MRCK isoforms alpha and beta with phorbol ester. The MRCK C1 domains bind [20-H-3] phorbol 12,13-dibutyrate with K-d values of 10 and 17 nM, respectively, reflecting 60-90-fold weaker affinity compared with the protein kinase C delta C1b domain. In contrast to binding by the C1b domain of PKC delta, the binding by the C1 domains of MRCK alpha and beta was fully dependent on the presence of phosphatidylserine. Comparison of ligand binding selectivity showed resemblance to that by the C1b domain of PKC alpha and marked contrast to that of the C1b domain of PKC delta. In intact cells, as in the binding assays, the MRCK C1 domains required 50-100-fold higher concentrations of phorbol ester for induction of membrane translocation. We conclude that additional structural elements within the MRCK structure are necessary if the C1 domains of MRCK are to respond to phorbol ester at concentrations comparable with those that modulate PKC. C1 [Choi, Sung Hee; Czifra, Gabriella; Kedei, Noemi; Lewin, Nancy E.; Lazar, Jozsef; Pu, Yongmei; Blumberg, Peter M.] NCI, Lab Canc Biol & genet, Natl Inst Hlth, Bethesda, MD 20892 USA. [Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, Natl Inst Hlth, Frederick, MD 21701 USA. RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & genet, Natl Inst Hlth, Bldg 37 Rm 4048B 37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM blumberg@dc37a.nci.nih.gov FU Intramural NIH HHS NR 31 TC 18 Z9 18 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 APR 18 PY 2008 VL 283 IS 16 BP 10543 EP 10549 DI 10.1074/jbc.M707463200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 287CQ UT WOS:000254894700036 PM 18263588 ER PT J AU Zhang, HF Bosch-Marce, M Shimoda, LA Tan, YS Baek, JH Wesley, JB Gonzalez, FJ Semenza, GL AF Zhang, Huafeng Bosch-Marce, Marta Shimoda, Larissa A. Tan, Yee Sun Baek, Jin Hyen Wesley, Jacob B. Gonzalez, Frank J. Semenza, Gregg L. TI Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCIBLE FACTOR 1-ALPHA; BH3-ONLY PROTEIN; GENE-EXPRESSION; COMPLEX-III; HIF-1; OXYGEN; TRANSCRIPTION; PATHWAY; FACTOR-1-ALPHA; HIF-1-ALPHA AB Autophagy is a process by which cytoplasmic organelles can be catabolized either to remove defective structures or as a means of providing macromolecules for energy generation under conditions of nutrient starvation. In this study we demonstrate that mitochondrial autophagy is induced by hypoxia, that this process requires the hypoxia-dependent factor-1-dependent expression of BNIP3 and the constitutive expression of Beclin-1 and Atg5, and that in cells subjected to prolonged hypoxia, mitochondrial autophagy is an adaptive metabolic response which is necessary to prevent increased levels of reactive oxygen species and cell death. C1 [Zhang, Huafeng; Bosch-Marce, Marta; Tan, Yee Sun; Baek, Jin Hyen; Wesley, Jacob B.; Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Vasc Program, Inst Cell Engn, Baltimore, MD 21205 USA. [Zhang, Huafeng; Bosch-Marce, Marta; Tan, Yee Sun; Baek, Jin Hyen; Wesley, Jacob B.; Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Shimoda, Larissa A.; Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Semenza, GL (reprint author), Broadway Res Bldg,Suite 671,733 N Broadway, Baltimore, MD 21205 USA. EM gsemenza@jhmi.edu RI Zhang, Huafeng/A-7188-2012 FU NCI NIH HHS [P50-CA103175] NR 45 TC 660 Z9 686 U1 12 U2 53 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 APR 18 PY 2008 VL 283 IS 16 BP 10892 EP 10903 DI 10.1074/jbc.M800102200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 287CQ UT WOS:000254894700071 PM 18281291 ER PT J AU Hu, J Hu, K Williams, DC Komlosh, ME Cai, M Clore, GM AF Hu, Jun Hu, Kaifeng Williams, David C., Jr. Komlosh, Michal E. Cai, Mengli Clore, G. Marius TI Solution NMR structures of productive and non-productive complexes between the A and B domains of the cytoplasmic subunit of the mannose transporter of the Escherichia coli phosphotransferase system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHORYL TRANSFER COMPLEX; RESTRAINED MOLECULAR-DYNAMICS; RESIDUAL DIPOLAR COUPLINGS; NUCLEAR-MAGNETIC-RESONANCE; BACTERIAL PHOSPHOENOLPYRUVATE; 3-DIMENSIONAL STRUCTURES; STRUCTURE REFINEMENT; STEREOCHEMICAL COURSE; DISTANCE GEOMETRY; PROTEIN COMPLEXES AB Solution structures of complexes between the isolated A (IIA(Man)) and B (IIBMan) domains of the cytoplasmic component of the mannose transporter of Escherichia coli have been solved by NMR. The complex of wild-type IIA(Man) and IIBMan is a mixture of two species comprising a productive, phosphoryl transfer competent complex and a non-productive complex with the two active site histidines, His-10 of IIA(Man) and His-175 of IIBMan, separated by similar to 25 angstrom. Mutation of the active site histidine, His-10, of IIA(Man) to a glutamate, to mimic phosphorylation, results in the formation of a single productive complex. The apparent equilibrium dissociation constants for the binding of both wild-type and H10E IIA(Man) to IIBMan are approximately the same (K-D similar to 0.5mM). The productive complex can readily accommodate a transition state involving a pentacoordinate phosphoryl group with trigonal bipyramidal geometry bonded to the N epsilon 2 atom of His-10 of IIA(Man) and the N delta 1 atom of His-175 of IIBMan with negligible (< 0.2 angstrom) local backbone conformational changes in the immediate vicinity of the active site. The non-productive complex is related to the productive one by a similar to 90 rotation and similar to 37 angstrom translation of IIBMan relative to IIA(Man), leaving the active site His-175 of IIBMan fully exposed to solvent in the non-productive complex. The interaction surface on IIA(Man) for the non-productive complex comprises a subset of residues used in the productive complex and in both cases involves both subunits of IIA(Man). The selection of the productive complex by IIA(Man)(H10E) can be attributed to neutralization of the positively charged Arg-172 of IIBMan at the center of the interface. The non-productive IIA(Man)-IIBMan complex may possibly be relevant to subsequent phosphoryl transfer from His-175 of IIBMan to the incoming sugar located on the transmembrane IICMan-IIDMan complex. C1 [Hu, Jun; Hu, Kaifeng; Williams, David C., Jr.; Komlosh, Michal E.; Cai, Mengli; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,B1-301, Bethesda, MD 20892 USA. EM mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU Intramural NIH HHS NR 63 TC 16 Z9 16 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 APR 18 PY 2008 VL 283 IS 16 BP 11024 EP 11037 DI 10.1074/jbc.M800312200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 287CQ UT WOS:000254894700083 PM 18270202 ER PT J AU Tsai, CJ del Sol, A Nussinov, R AF Tsai, Chung-Jung del Sol, Antonio Nussinov, Ruth TI Allostery: Absence of a change in shape does not imply that allostery is not at play SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Review DE residue communication; thermodynamics; entropy; network; rewiring ID LIGAND-BINDING; DIHYDROFOLATE-REDUCTASE; FUNCTIONAL TRANSITIONS; DYNAMIC ALLOSTERY; PROTEIN ALLOSTERY; BIOTIN REPRESSOR; NMR-SPECTROSCOPY; PLAUSIBLE MODEL; LOCAL MOTIONS; COOPERATIVITY AB Allostery is essential for controlled catalysis, signal transmission, receptor trafficking, turning genes on and off, and apoptosis. It governs the organism's response to environmental and metabolic cues, dictating transient partner interactions in the cellular network. Textbooks taught us that allostery is a change of shape at one site on the protein surface brought about by ligand binding to another. For several years, it has been broadly accepted that the change of shape is not induced; rather, it is observed simply because a larger protein population presents it. Current data indicate that while side chains can reorient and rewire, allostery may not even involve a change of (backbone) shape. Assuming that the enthalpy change does not reverse the free-energy change due to the change in entropy, entropy is mainly responsible for binding. C1 [Tsai, Chung-Jung; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. [del Sol, Antonio] Fujirebio Inc, Div Res & Dev, Bioinformat Res Unit, Hachioji, Tokyo 1920031, Japan. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Ctr Canc Res Nanobiol, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov FU Intramural NIH HHS [Z01 BC010440-06]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 54 TC 278 Z9 280 U1 4 U2 30 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 18 PY 2008 VL 378 IS 1 BP 1 EP 11 DI 10.1016/j.jmb.2008.02.034 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 293XH UT WOS:000255368200001 PM 18353365 ER PT J AU Liu, L Botos, I Wang, Y Leonard, JN Shiloach, J Segal, DM Davies, DR AF Liu, Lin Botos, Istvan Wang, Yan Leonard, Joshua N. Shiloach, Joseph Segal, David M. Davies, David R. TI Structural basis of toll-like receptor 3 signaling with double-stranded RNA SO SCIENCE LA English DT Article ID CRYSTAL-STRUCTURE; BINDING; RECOGNITION AB Toll- like receptor 3 ( TLR3) recognizes double- stranded RNA ( dsRNA), a molecular signature of most viruses, and triggers inflammatory responses that prevent viral spread. TLR3 ectodomains ( ECDs) dimerize on oligonucleotides of at least 40 to 50 base pairs in length, the minimal length required for signal transduction. To establish the molecular basis for ligand binding and signaling, we determined the crystal structure of a complex between two mouse TLR3- ECDs and dsRNA at 3.4 angstrom resolution. Each TLR3- ECD binds dsRNA at two sites located at opposite ends of the TLR3 horseshoe, and an intermolecular contact between the two TLR3- ECD C- terminal domains coordinates and stabilizes the dimer. This juxtaposition could mediate downstream signaling by dimerizing the cytoplasmic Toll interleukin- 1 receptor ( TIR) domains. The overall shape of the TLR3- ECD does not change upon binding to dsRNA. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Yan; Leonard, Joshua N.; Segal, David M.] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Shiloach, Joseph] NIDDKD, Biotechnol Unit, Bethesda, MD 20892 USA. RP Davies, DR (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM david.davies@nih.gov RI Leonard, Joshua/B-7649-2009 FU Intramural NIH HHS [Z01 BC009254-33] NR 15 TC 356 Z9 369 U1 4 U2 30 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 APR 18 PY 2008 VL 320 IS 5874 BP 379 EP 381 DI 10.1126/science.1155406 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 288ZZ UT WOS:000255026100045 PM 18420935 ER PT J AU Ebert, AM McAnelly, CA Srinivasan, A Mueller, RL Garrity, DB Garrity, DM AF Ebert, Alicia M. McAnelly, Catherine A. Srinivasan, Ashok Mueller, Rachel Lockridge Garrity, David B. Garrity, Deborah M. TI The calcium channel beta 2 (CACNB2) subunit repertoire in teleosts SO BMC MOLECULAR BIOLOGY LA English DT Article ID CHANNEL BETA-SUBUNIT; DEPENDENT CALCIUM-CHANNELS; RAY-FINNED FISH; CA2+ CHANNELS; CARDIAC DEVELOPMENT; TARGETED DISRUPTION; REGIONAL EXPRESSION; GENOME DUPLICATION; CA(V)1.2 CHANNEL; ALPHA(1) SUBUNIT AB Background: Cardiomyocyte contraction is initiated by influx of extracellular calcium through voltage-gated calcium channels. These oligomeric channels utilize auxiliary beta subunits to chaperone the pore-forming alpha subunit to the plasma membrane, and to modulate channel electrophysiology [1]. Several beta subunit family members are detected by RT-PCR in the embryonic heart. Null mutations in mouse beta 2, but not in the other three beta family members, are embryonic lethal at E10.5 due to defects in cardiac contractility [2]. However, a drawback of the mouse model is that embryonic heart rhythm is difficult to study in live embryos due to their intra-uterine development. Moreover, phenotypes may be obscured by secondary effects of hypoxia. As a first step towards developing a model for contributions of beta subunits to the onset of embryonic heart rhythm, we characterized the structure and expression of beta 2 subunits in zebrafish and other teleosts. Results: Cloning of two zebrafish beta 2 subunit genes (beta 2.1 and beta 2.2) indicated they are membrane-associated guanylate kinase (MAGUK)-family genes. Zebrafish beta 2 genes show high conservation with mammals within the SH3 and guanylate kinase domains that comprise the "core" of MAGUK proteins, but beta 2.2 is much more divergent in sequence than beta 2.1. Alternative splicing occurs at the N-terminus and within the internal HOOK domain. In both beta 2 genes, alternative short ATG-containing first exons are separated by some of the largest introns in the genome, suggesting that individual transcript variants could be subject to independent cis-regulatory control. In the Tetraodon nigrovidis and Fugu rubripes genomes, we identified single beta 2 subunit gene loci. Comparative analysis of the teleost and human beta 2 loci indicates that the short 5' exon sequences are highly conserved. A subset of 5' exons appear to be unique to teleost genomes, while others are shared with mammals. Alternative splicing is temporally and spatially regulated in embryo and adult. Moreover, a different subset of spliced beta 2 transcript variants is detected in the embryonic heart compared to the adult. Conclusion: These studies refine our understanding of beta 2 subunit diversity arising from alternative splicing, and provide the groundwork for functional analysis of beta 2 subunit diversity in the embryonic heart. C1 [Ebert, Alicia M.; McAnelly, Catherine A.; Mueller, Rachel Lockridge; Garrity, David B.; Garrity, Deborah M.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. [Srinivasan, Ashok] NHLBI, NIH, Bethesda, MD 20892 USA. RP Garrity, DM (reprint author), Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. EM amebert@lamar.colostate.edu; cmcanell@holly.colostate.edu; srinivasana@mail.nih.gov; rachel.mueller@colostate.edu; david.garrity@colostate.edu; deborah.garrity@colostate.edu NR 85 TC 4 Z9 4 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2199 J9 BMC MOL BIOL JI BMC Mol. Biol. PD APR 17 PY 2008 VL 9 AR 38 DI 10.1186/1471-2199-9-38 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 296SU UT WOS:000255566900001 PM 18419826 ER PT J AU Tyson, JE Parikh, NA Langer, J Green, C Higgins, RD AF Tyson, Jon E. Parikh, Nehal A. Langer, John Green, Charles Higgins, Rosemary D. CA Natl Inst Child Hlth TI Intensive care for extreme prematurity - Moving beyond gestational age SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BIRTH-WEIGHT INFANTS; GROSS MOTOR FUNCTION; PERINATAL-PERIOD; DATING FORMULAS; CEREBRAL-PALSY; VIABILITY; POPULATION; CHILDREN; DELIVERY; DETERMINANTS AB Background: Decisions regarding whether to administer intensive care to extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients. Methods: We prospectively studied a cohort of 4446 infants born at 22 to 25 weeks' gestation (determined on the basis of the best obstetrical estimate) in the Neonatal Research Network of the National Institute of Child Health and Human Development to relate risk factors assessable at or before birth to the likelihood of survival, survival without profound neurodevelopmental impairment, and survival without neurodevelopmental impairment at a corrected age of 18 to 22 months. Results: Among study infants, 3702 (83%) received intensive care in the form of mechanical ventilation. Among the 4192 study infants (94%) for whom outcomes were determined at 18 to 22 months, 49% died, 61% died or had profound impairment, and 73% died or had impairment. In multivariable analyses of infants who received intensive care, exposure to antenatal corticosteroids, female sex, singleton birth, and higher birth weight (per each 100-g increment) were each associated with reductions in the risk of death and the risk of death or profound or any neurodevelopmental impairment; these reductions were similar to those associated with a 1-week increase in gestational age. At the same estimated likelihood of a favorable outcome, girls were less likely than boys to receive intensive care. The outcomes for infants who underwent ventilation were better predicted with the use of the above factors than with use of gestational age alone. Conclusions: The likelihood of a favorable outcome with intensive care can be better estimated by consideration of four factors in addition to gestational age: sex, exposure or nonexposure to antenatal corticosteroids, whether single or multiple birth, and birth weight. (ClinicalTrials.gov numbers, NCT00063063 and NCT00009633.). C1 [Tyson, Jon E.; Parikh, Nehal A.; Green, Charles] Univ Texas Houston, Sch Med, Ctr Clin Res & Evidence Based Med, Houston, TX 77030 USA. [Langer, John] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Higgins, Rosemary D.] NICHHD, Bethesda, MD 20892 USA. RP Tyson, JE (reprint author), Univ Texas Houston, Sch Med, Ctr Clin Res & Evidence Based Med, MSB 2-106,6431 Fannin St, Houston, TX 77030 USA. EM jon.e.tyson@uth.tmc.edu RI Benneyworth, Brian/A-4667-2009 OI Benneyworth, Brian/0000-0002-4692-5303 FU NCATS NIH HHS [UL1 TR000454]; NCRR NIH HHS [M01 RR 00044, M01 RR 00039, M01 RR 00070, M01 RR 00125, M01 RR 00750, M01 RR 00997, M01 RR 06022, M01 RR 08084, M01 RR000039, M01 RR000044, M01 RR000070, M01 RR000125, M01 RR000750, M01 RR000997, M01 RR006022, M01 RR008084, UL1 RR024148, UL1 RR24148]; NICHD NIH HHS [U01 HD036790, U01 HD36790, U10 HD021364, U10 HD021373, U10 HD021385, U10 HD021397, U10 HD027851, U10 HD027853, U10 HD027856, U10 HD027871, U10 HD027880, U10 HD027904, U10 HD034167, U10 HD034216, U10 HD040461, U10 HD040492, U10 HD040498, U10 HD040521, U10 HD040689, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34216, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40521, U10 HD40689]; NINDS NIH HHS [5K23NS048152-02, K23 NS048152, K23 NS048152-04] NR 40 TC 378 Z9 391 U1 1 U2 6 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 APR 17 PY 2008 VL 358 IS 16 BP 1672 EP 1681 DI 10.1056/NEJMoa073059 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 288DO UT WOS:000254966600005 PM 18420500 ER PT J AU Dawson, HD Collins, G Pyle, R Key, M Taub, DD AF Dawson, Harry D. Collins, Gary Pyle, Robert Key, Michael Taub, Dennis D. TI The Retinoic Acid Receptor-alpha mediates human T-cell activation and Th2 cytokine and chemokine production SO BMC IMMUNOLOGY LA English DT Article ID DIFFERENTIATION IN-VITRO; X-RECEPTOR; SELECTIVE RETINOIDS; GENE-EXPRESSION; CARCINOMA-CELLS; DOWN-REGULATION; RAR-ALPHA; VITAMIN-A; RXR-ALPHA; LYMPHOCYTES AB Background: We have recently demonstrated that all- trans-retinoic acid (ATRA) and 9-cisretinoic acid (9-cis RA) promote IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-gamma. and TNF-alpha expression by activated human T cells and reduces the synthesis of IL-12p70 from accessory cells. Here, we have demonstrated that the observed effects using ATRA and 9-cis RA are shared with the clinically useful RAR ligand, 13-cis retinoic acid (13-cis RA), and the retinoic acid receptor-alpha (RAR-alpha)-selective agonist, AM580 but not with the RAR-beta/gamma. ligand, 4-hydroxyphenylretinamide (4-HPR). Results: The increase in type 2 cytokine production by these retinoids correlated with the expression of the T cell activation markers, CD69 and CD38. The RAR-alpha-selective agonist, AM580 recapitulated all of the T cell activation and type 2 cytokine-inducing effects of ATRA and 9-cis-RA, while the RAR-alpha-selective antagonist, RO 41 -5253, inhibited these effects. Conclusion: These results strongly support a role for RAR-alpha engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production. C1 [Collins, Gary; Pyle, Robert; Key, Michael; Taub, Dennis D.] NIA, Immunol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. [Dawson, Harry D.] USDA, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA. RP Taub, DD (reprint author), NIA, Immunol Lab, Gerontol Res Ctr, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM harry.dawson@ars.usda.gov; collinsg@grc.nia.nih.gov; pyler@grc.nia.nih.gov; keym@grc.nia.nih.gov; taubd@grc.nia.nih.gov RI Dawson, Harry/H-8242-2013 FU Intramural NIH HHS NR 61 TC 27 Z9 28 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD APR 16 PY 2008 VL 9 AR 16 DI 10.1186/1471-2172-9-16 PG 14 WC Immunology SC Immunology GA 308EG UT WOS:000256370500001 PM 18416830 ER PT J AU Cassina, P Cassina, A Pehar, M Castellanos, R Gandelman, M de Leon, A Robinson, KM Mason, RP Beckman, JS Barbeito, L Radi, R AF Cassina, Patricia Cassina, Adriana Pehar, Mariana Castellanos, Raquel Gandelman, Mandi de Leon, Andres Robinson, Kristine M. Mason, Ronald P. Beckman, Joseph S. Barbeito, Luis Radi, Rafael TI Mitochondrial dysfunction in S0D1(G93A)-bearing astrocytes promotes motor neuron degeneration: Prevention by mitochondrial-targeted antioxidants SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mitochondria; ALS; astrocytes; S0D1; free radicals; antioxidants ID AMYOTROPHIC-LATERAL-SCLEROSIS; PROTEIN-TYROSINE NITRATION; SPINAL-CORD ASTROCYTES; GROWTH-FACTOR-I; SUPEROXIDE-DISMUTASE; NITRIC-OXIDE; ELECTRON-TRANSPORT; HEART-MITOCHONDRIA; TRANSGENIC MICE; APOPTOSIS AB Mitochondrial dysfunction and oxidative stress contribute to motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Recent reports indicate that astrocytes expressing the mutations of superoxide dismutase- 1 (SOD1) may contribute to motor neuron injury in ALS. Here, we provide evidence that mitochondrial dysfunction in S0D1(G93A) rat astrocytes causes astrocytes to induce apoptosis of motor neurons. Mitochondria from S0D1(G93A) rat astrocytes displayed a defective respiratory function, including decreased oxygen consumption, lack of ADP-dependent respiratory control, and decreased membrane potential. Protein 3-nitrotyrosine was detected immunochemically in mitochondrial proteins from S0D1(G93A) astrocytes, suggesting that mitochondrial defects were associated with nitroxidative damage. Furthermore, superoxide radical formation in mitochondria was increased in S0D1(G93A) astrocytes. Similar defects were found in mitochondria isolated from the spinal cord of S0D1(G93A) rats, and pretreatment of animals with the spin trap 5,5-dimethyl-1-pyrroline N-oxide restored mitochondrial function, forming adducts with mitochondrial proteins in vivo. As shown previously, S0D1(G93A) astrocytes induced death of motor neurons in cocultures, compared with nontransgenic ones. This behavior was recapitulated when nontransgenic astrocytes were treated with mitochondrial inhibitors. Remarkably, motor neuron loss was prevented by preincubation of S0D1(G93A) astrocytes with antioxidants and nitric oxide synthase inhibitors. In particular, low concentrations (similar to 10 nM) of two mitochondrial-targeted antioxidants, ubiquinone and carboxy-proxyl nitroxide, each covalently coupled to a triphenylphosphonium cation (Mito-Q and Mito-CP, respectively), prevented mitochondrial dysfunction, reduced superoxide production in S0D1(G93A) astrocytes, and restored motor neuron survival. Together, our results indicate that mitochondrial dysfunction in astrocytes critically influences motor neuron survival and support the potential pharmacological utility of mitochondrial-targeted antioxidants in ALS treatment. C1 [Cassina, Patricia; Castellanos, Raquel; Gandelman, Mandi; de Leon, Andres] Univ Republica, Fac Med, Dept Histol, Montevideo 11800, Uruguay. [Cassina, Adriana; Radi, Rafael] Univ Republica, Fac Med, Dept Bioquim, Montevideo 11800, Uruguay. [Cassina, Patricia; Cassina, Adriana; Barbeito, Luis; Radi, Rafael] Univ Republica, Fac Med, Ctr Free Rad & Biomed Res, Montevideo 11800, Uruguay. [Pehar, Mariana; Barbeito, Luis] Inst Invest Biol Clemente Estable, Montevideo 11600, Uruguay. [Gandelman, Mandi; de Leon, Andres; Barbeito, Luis] Inst Pasteur, Neurodegenerat Lab, Montevideo 11400, Uruguay. [Mason, Ronald P.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Robinson, Kristine M.; Beckman, Joseph S.] Oregon State Univ, Linus Pauling Inst, Dept Biochem & Biophys, Corvallis, OR 97331 USA. RP Cassina, P (reprint author), Univ Republica, Fac Med, Dept Histol, Ave Gen Flores 2125, Montevideo 11800, Uruguay. EM pcassina@fmed.edu.uy; rradi@fmed.edu.uy FU Howard Hughes Medical Institute; NIEHS NIH HHS [ES00240] NR 56 TC 134 Z9 136 U1 1 U2 13 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 APR 16 PY 2008 VL 28 IS 16 BP 4115 EP 4122 DI 10.1523/JNEUROSCI.5308-07.2008 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 288UY UT WOS:000255012500004 PM 18417691 ER PT J AU Engel, S Skoumbourdis, AP Childress, J Neumann, S Deschamps, JR Thomas, CJ Colson, AO Costanzi, S Gershengorn, MC AF Engel, Stanislav Skoumbourdis, Amanda P. Childress, John Neumann, Susanne Deschamps, Jeffrey R. Thomas, Craig J. Colson, Anny-Odile Costanzi, Stefano Gershengorn, Marvin C. TI A virtual screen for diverse ligands: Discovery of selective G protein-coupled receptor antagonists SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; CRYSTAL-STRUCTURE; TRH RECEPTOR; BINDING-AFFINITY; REFINED MODEL; ANALOGS; BIOLOGY; IDENTIFICATION; SIMULATIONS; INHIBITORS AB Virtual screening has become a major focus of bioactive small molecule lead identification, and reports of agonists and antagonists discovered via virtual methods are becoming more frequent. G protein-coupled receptors (GPCRs) are the one class of protein targets for which success with this approach has been limited. This is likely due to the paucity of detailed experimental information describing GPCR structure and the intrinsic function-associated structural flexibility of GPCRs which present major challenges in the application of receptor-based virtual screening. Here we describe an in silico methodology that diminishes the effects of structural uncertainty, allowing for more inclusive representation of a potential docking interaction with exogenous ligands. Using this approach, we screened one million compounds from a virtual database, and a diverse subgroup of 100 compounds was selected, leading to experimental identification of five structurally diverse antagonists of the thyrotropin-releasing hormone receptors (TRH-R1 and TRH-R2). The chirality of the most potent chemotype was demonstrated to be important in,its binding affinity to TRH receptors; the most potent stereoisomer was noted to have a 13-fold selectivity for TRH-R1 over TRH-R2. A comprehensive mutational analysis of key amino acid residues that form the putative binding pocket of TRH receptors further verified the binding modality of these small molecule antagonists. The described virtual screening approach may prove applicable in the search for novel small molecule agonists and antagonists of other GPCRs. C1 [Engel, Stanislav; Childress, John; Neumann, Susanne; Colson, Anny-Odile; Costanzi, Stefano; Gershengorn, Marvin C.] NIDDKD, Natl Inst Hlth, Clin Endocrinol Branch, Bethesda, MD 20892 USA. [Engel, Stanislav; Childress, John; Neumann, Susanne; Colson, Anny-Odile; Costanzi, Stefano; Gershengorn, Marvin C.] NIDDKD, Natl Inst Hlth, Biomolec Modelling Lab, Bethesda, MD 20892 USA. [Skoumbourdis, Amanda P.; Thomas, Craig J.] NHGRI, NIH, Chem Genom Ctr, Natl Inst Hlth, Rockville, MD 20850 USA. [Deschamps, Jeffrey R.] USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Gershengorn, MC (reprint author), NIDDKD, Natl Inst Hlth, Clin Endocrinol Branch, 50 S Dr, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov RI Engel, Stanislav/G-2799-2013; Costanzi, Stefano/G-8990-2013; OI Deschamps, Jeffrey/0000-0001-5845-0010; Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS; NIDA NIH HHS [Y1-DA6002-02] NR 49 TC 59 Z9 60 U1 0 U2 3 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 APR 16 PY 2008 VL 130 IS 15 BP 5115 EP 5123 DI 10.1021/ja0776201 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 287RA UT WOS:000254933000035 PM 18357984 ER PT J AU Chaturvedi, AK Engels, EA Gilbert, ES Chen, BE Storm, H Lynch, CF Hall, P Langmark, F Pukkala, E Kaijser, M Andersson, M Fossa, SD Joensuu, H Boice, JD Kleinerman, RA Travis, LB AF Chaturvedi, Anil K. Engels, Eric A. Gilbert, Ethel S. Chen, Bingshu E. Storm, Hans Lynch, Charles F. Hall, Per Langmark, Froydis Pukkala, Eero Kaijser, Magnus Andersson, Michael Fossa, Sophie D. Joensuu, Heikki Boice, John D., Jr. Kleinerman, Ruth A. Travis, Lois B. TI Re: Second cancers among 104760 survivors of cervical cancer: Evaluation of long-term risk - Reply SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Chaturvedi, Anil K.] Natl Inst Hlth, Natl Canc Inst, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,Viral Epidemiol Branch, Rockville, MD 20852 USA. [Chaturvedi, Anil K.; Engels, Eric A.; Gilbert, Ethel S.; Chen, Bingshu E.; Kleinerman, Ruth A.; Travis, Lois B.] Natl Inst Hlth, Natl Canc Inst, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Storm, Hans; Andersson, Michael] Danish Canc Soc, Copenhagen, Denmark. [Lynch, Charles F.] Univ Iowa, Iowa City, IA USA. [Hall, Per; Kaijser, Magnus] Karolinska Inst, Stockholm, Sweden. [Langmark, Froydis; Fossa, Sophie D.] Canc Registry Norway, Oslo, Norway. [Pukkala, Eero] Finnish Canc Registry, FIN-00170 Helsinki, Finland. [Joensuu, Heikki] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Boice, John D., Jr.] Int Epidemiol Inst, Rockville, MD USA. [Boice, John D., Jr.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RP Chaturvedi, AK (reprint author), Natl Inst Hlth, Natl Canc Inst, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,Viral Epidemiol Branch, 6120 Execut Blvd,EPS 7072, Rockville, MD 20852 USA. EM chaturva@mail.nih.gov NR 3 TC 0 Z9 0 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 APR 16 PY 2008 VL 100 IS 8 BP 600 EP 601 DI 10.1093/jnci/djn086 PG 2 WC Oncology SC Oncology GA 290VW UT WOS:000255151900020 ER PT J AU Firestein, R Blander, G Michan, S Oberdoerffer, P Ogino, S Campbell, J Bhimavarapu, A Luikenhuis, S de Cabo, R Fuchs, C Hahn, WC Guarente, LP Sinclair, DA AF Firestein, Ron Blander, Gil Michan, Shaday Oberdoerffer, Philipp Ogino, Shuji Campbell, Jennifer Bhimavarapu, Anupama Luikenhuis, Sandra de Cabo, Rafael Fuchs, Charles Hahn, William C. Guarente, Leonard P. Sinclair, David A. TI The SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growth SO PLOS ONE LA English DT Article AB Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same pathways might be offset by increased cancer risk on account of their propensity to boost cell survival. The Sir2/SIRT1 family of NAD(+)-dependent deacetylases is proposed to underlie the health benefits of calorie restriction (CR), a diet that broadly suppresses cancer in mammals. Here we show that CR induces a two-fold increase SIRT1 expression in the intestine of rodents and that ectopic induction of SIRT1 in a beta-catenin-driven mouse model of colon cancer significantly reduces tumor formation, proliferation, and animal morbidity in the absence of CR. We show that SIRT1 deacetylates beta-catenin and suppresses its ability to activate transcription and drive cell proliferation. Moreover, SIRT1 promotes cytoplasmic localization of the otherwise nuclear-localized oncogenic form of beta-catenin. Consistent with this, a significant inverse correlation was found between the presence of nuclear SIRT1 and the oncogenic form of beta-catenin in 81 human colon tumor specimens analyzed. Taken together, these observations show that SIRT1 suppresses intestinal tumor formation in vivo and raise the prospect that therapies targeting SIRT1 may be of clinical use in beta-catenin-driven malignancies. C1 [Firestein, Ron; Michan, Shaday; Oberdoerffer, Philipp; Campbell, Jennifer; Luikenhuis, Sandra; Sinclair, David A.] Harvard Univ, Sch Med, Dept Pathol, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA. [Blander, Gil; Bhimavarapu, Anupama; Guarente, Leonard P.] Massachusetts Inst Technol, Dept Biol, Cambridge, MA USA. [Firestein, Ron; Ogino, Shuji] Brigham & Womens Hospital, Harvard Med Sch, Dept Pathol, Boston, MA USA. [Firestein, Ron; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [de Cabo, Rafael] NIH, NIA, Lab Expt Gerontol, Bethesda, MD USA. [Firestein, Ron; Fuchs, Charles; Hahn, William C.] Massachusetts Inst Technol, Broad Inst Harvard, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Sinclair, DA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA. EM david_sinclair@hms.harvard.edu RI de Cabo, Rafael/E-7996-2010; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Sinclair, David/0000-0002-9936-436X; , rafael/0000-0003-2830-5693 FU NIH [T32]; Estee Lauder [postdoctoral fellowship]; National Space Biomedical Research Institute; Intramural Research Program of the NIH/NIA; Paul F. Glenn Foundation FX RF was supported by the NIH T32 Grant. GB by an Estee Lauder postdoctoral fellowship. PO by a National Space Biomedical Research Institute Grant. DAS, SO, CSF and LG by grants from NIH; RD in part by the Intramural Research Program of the NIH/NIA. DS is also supported by a gift from the Paul F. Glenn Foundation. NR 33 TC 318 Z9 337 U1 1 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 APR 16 PY 2008 VL 3 IS 4 AR e2020 DI 10.1371/journal.pone.0002020 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 371XZ UT WOS:000260867300029 PM 18414679 ER PT J AU Volkow, ND Fowler, JS Wang, GJ Telang, F Logan, J Wong, C Ma, J Pradhan, K Benveniste, H Swanson, JM AF Volkow, Nora D. Fowler, Joanna S. Wang, Gene-Jack Telang, Frank Logan, Jean Wong, Christopher Ma, Jim Pradhan, Kith Benveniste, Helene Swanson, James M. TI Methylphenidate Decreased the Amount of Glucose Needed by the Brain to Perform a Cognitive Task SO PLOS ONE LA English DT Article AB The use of stimulants (methylphenidate and amphetamine) as cognitive enhancers by the general public is increasing and is controversial. It is still unclear how they work or why they improve performance in some individuals but impair it in others. To test the hypothesis that stimulants enhance signal to noise ratio of neuronal activity and thereby reduce cerebral activity by increasing efficiency, we measured the effects of methylphenidate on brain glucose utilization in healthy adults. We measured brain glucose metabolism (using Positron Emission Tomography and 2-deoxy-2[18F] fluoro-D-glucose) in 23 healthy adults who were tested at baseline and while performing an accuracy-controlled cognitive task (numerical calculations) given with and without methylphenidate (20 mg, oral). Sixteen subjects underwent a fourth scan with methylphenidate but without cognitive stimulation. Compared to placebo methylphenidate significantly reduced the amount of glucose utilized by the brain when performing the cognitive task but methylphenidate did not affect brain metabolism when given without cognitive stimulation. Whole brain metabolism when the cognitive task was given with placebo increased 21% whereas with methylphenidate it increased 11% (50% less). This reflected both a decrease in magnitude of activation and in the regions activated by the task. Methylphenidate's reduction of the metabolic increases in regions from the default network (implicated in mind-wandering) was associated with improvement in performance only in subjects who activated these regions when the cognitive task was given with placebo. These results corroborate prior findings that stimulant medications reduced the magnitude of regional activation to a task and in addition document a "focusing'' of the activation. This effect may be beneficial when neuronal resources are diverted (i.e., mind-wandering) or impaired (i.e., attention deficit hyperactivity disorder), but it could be detrimental when brain activity is already optimally focused. This would explain why methylphenidate has beneficial effects in some individuals and contexts and detrimental effects in others. C1 [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. [Volkow, Nora D.; Telang, Frank; Ma, Jim] Natl Inst Alcohol Abuse & Alcoholism, Bethesda, MD USA. [Fowler, Joanna S.; Wang, Gene-Jack; Logan, Jean; Wong, Christopher; Pradhan, Kith; Benveniste, Helene] Brookhaven Natl Lab, Med Dept, Upton, NY USA. [Swanson, James M.] Univ Calif Irvine, Child Dev Ctr, Irvine, CA USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov OI Logan, Jean/0000-0002-6993-9994 FU Intramural Research Program of the NIH (National Institutes on Alcoholism and Alcohol Abuse); Department of Energy Office of Biological and Environmental Research [DE-AC01-76CH00016] FX This research was supported in part by the Intramural Research Program of the NIH (National Institutes on Alcoholism and Alcohol Abuse) and by the Department of Energy (Office of Biological and Environmental Research, contract DE-AC01-76CH00016). NR 35 TC 52 Z9 52 U1 1 U2 8 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 APR 16 PY 2008 VL 3 IS 4 AR e2017 DI 10.1371/journal.pone.0002017 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 371XZ UT WOS:000260867300026 PM 18414677 ER PT J AU Lo, CY Wu, ZQ Misplon, JA Price, GE Pappas, C Kong, WP Turnpey, TM Epstein, SL AF Lo, Chia-Yun Wu, Zhengqi Misplon, Julia A. Price, Graeme E. Pappas, Claudia Kong, Wing-Pui Turnpey, Terrence M. Epstein, Suzanne L. TI Comparison of vaccines for induction of heterosubtypic immunity to influenza A virus: Cold-adapted vaccine versus DNA prime-adenovirus boost strategies SO VACCINE LA English DT Article DE influenza; pandemic; heterosubtypic immunity ID HETEROTYPIC IMMUNITY; H5N1 VIRUSES; T-CELLS; RELATIVE IMMUNOGENICITY; INACTIVATED VACCINES; MATRIX PROTEIN-2; DONOR STRAINS; M2 PROTEIN; MICE; LIVE AB Influenza epidemics or pandemics can arise for which strain- or subtype-matched vaccines are unavailable. Heterosubtypic immunity (Het-1) targeting conserved influenza A antigens could reduce morbidity and mortality during preparation of matched vaccines. Various vaccines inducing Het-I in animals have been studied separately using different viruses and conditions, but effectiveness for inducing Het-1 has not been directly compared. The present studies compared immunization with cold-adapted (ca) viruses to DNA prime-recombinant adenovirus (rAd) boost vaccination to conserved antigens nucleoprotein (NP), matrix-2 (M2), or A/NP+M2. Both ca and DNA-rAd vaccinations induced antibody and T cell responses, and protected against lethal H1N1 challenge. Only A/NP+M2 DNA-rAd protected against challenge with highly pathogenic A/Vietnam/1203/2004 (H5N1); ca vaccine did not. Existing ca vaccines may provide some Het-1, but experimental vaccination focusing on conserved antigens was more effective in this model for protection against a divergent, highly pathogenic virus. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Lo, Chia-Yun; Wu, Zhengqi; Misplon, Julia A.; Price, Graeme E.; Epstein, Suzanne L.] US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, CBER, Rockville, MD 20852 USA. [Pappas, Claudia; Turnpey, Terrence M.] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Cooodinating Ctr Infect Dis, Atlanta, GA 30333 USA. [Kong, Wing-Pui] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Epstein, SL (reprint author), US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, CBER, 1401 Rockville Pike,HFM-730, Rockville, MD 20852 USA. EM suzanne.epstein@fda.hhs.gov NR 42 TC 53 Z9 59 U1 0 U2 3 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 APR 16 PY 2008 VL 26 IS 17 BP 2062 EP 2072 DI 10.1016/j.vaccine.2008.02.047 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 300LE UT WOS:000255824500004 PM 18378366 ER PT J AU Harper, S Lynch, J Meersman, SC Breen, N Davis, WW Reichman, ME AF Harper, Sam Lynch, John Meersman, Stephen C. Breen, Nancy Davis, William W. Reichman, Marsha E. TI An overview of methods for monitoring social disparities in cancer with an example using trends in lung cancer incidence by area-socioeconomic position and race-ethnicity, 1992-2004 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE epidemiologic methods; ethnic groups; health status disparities; lung neoplasms; socioeconomic factors ID HEALTH INEQUALITIES; RACIAL-DIFFERENCES; UNITED-STATES; MORTALITY; PATTERNS AB The authors provide an overview of methods for summarizing social disparities in health using the example of lung cancer. They apply four measures of relative disparity and three measures of absolute disparity to trends in US lung cancer incidence by area-socioeconomic position and race-ethnicity from 1992 to 2004. Among females, measures of absolute and relative disparity suggested that area-socioeconomic and race-ethnic disparities increased over these 12 years but differed widely with respect to the magnitude of the change. Among males, the authors found substantial disagreement among summary measures of relative disparity with respect to the magnitude and the direction of change in disparities. Among area-socioeconomic groups, the index of disparity increased by 47% and the relative concentration index decreased by 116%, while for race-ethnicity the index of disparity increased by 36% and the Theil index increased by 13%. The choice of a summary measure of disparity may affect the interpretation of changes in health disparities. Important issues to consider are the reference point from which differences are measured, whether to measure disparity on the absolute or relative scale, and whether to weight disparity measures by population size. A suite of indicators is needed to provide a clear picture of health disparity change. C1 [Harper, Sam; Lynch, John] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada. [Meersman, Stephen C.; Breen, Nancy; Davis, William W.; Reichman, Marsha E.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Harper, S (reprint author), McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, 1020 Pine Ave W,Room 17B, Montreal, PQ H3A 1A2, Canada. EM sam.harper@mcgill.ca RI Harper, Sam/A-3406-2008; Lynch, John/A-4797-2008 OI Harper, Sam/0000-0002-2767-1053; Lynch, John/0000-0003-2781-7902 FU NIMHD NIH HHS [L60 MD002460, L60 MD002460-01]; PHS HHS [263-MQ-611198] NR 30 TC 96 Z9 96 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 2008 VL 167 IS 8 BP 889 EP 899 DI 10.1093/aje/kwn016 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286VU UT WOS:000254874900001 PM 18344513 ER PT J AU Harper, S Lynch, J Meersman, SC Breen, N Davis, WW Reichman, ME AF Harper, Sam Lynch, John Meersman, Stephen C. Breen, Nancy Davis, William W. Reichman, Marsha E. TI Harper et al. respond to "Measuring Social Disparities in Health" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID SEGREGATION; DIMENSIONS C1 [Harper, Sam; Lynch, John] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada. [Meersman, Stephen C.; Breen, Nancy; Davis, William W.; Reichman, Marsha E.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Harper, S (reprint author), McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, 1020 Pine Ave W,Room 17B, Montreal, PQ H3A 1A2, Canada. EM sam.harper@mcgill.ca OI Harper, Sam/0000-0002-2767-1053 NR 15 TC 6 Z9 6 U1 0 U2 1 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 APR 15 PY 2008 VL 167 IS 8 BP 905 EP 907 DI 10.1093/aje/kwn015 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286VU UT WOS:000254874900003 ER PT J AU Larsson, SC Mannisto, S Virtanen, MJ Kontto, J Albanes, D Virtamo, J AF Larsson, Susanna C. Mannisto, Satu Virtanen, Mikko J. Kontto, Jukka Albanes, Demetrius Virtamo, Jarmo TI Folate, vitamin B-6, vitamin B-12, and methionine intakes and risk of stroke subtypes in male smokers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cerebral infarction; diet; folic acid; methionine; stroke; vitamin B 6; vitamin B 12 ID ISCHEMIC-HEART-DISEASE; FOLIC-ACID SUPPLEMENTATION; SERUM TOTAL HOMOCYSTEINE; CARDIOVASCULAR-DISEASE; VASCULAR-DISEASE; CONTROLLED-TRIAL; DIETARY-INTAKE; METAANALYSIS; PREVENTION; INFARCTION AB The associations of dietary folate, vitamin B-6, vitamin B-12, and methionine intakes with risk of stroke subtypes were examined among 26,556 male Finnish smokers, aged 50-69 years, enrolled in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Dietary intake was assessed at baseline by using a validated food frequency questionnaire. During a mean follow-up of 13.6 years, from 1985 through 2004, 2,702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages were identified from national registers. In analyses adjusting for age and cardiovascular risk factors, a high folate intake was associated with a statistically significant lower risk of cerebral infarction but not intracerebral or subarachnoid hemorrhages. The multivariate relative risk of cerebral infarction was 0.80 (95% confidence interval: 0.70, 0.91; p(trend) = 0.001) for men in the highest versus lowest quintile of folate intake. Vitamin B-6, vitamin B-12, and methionine intakes were not significantly associated with any subtype of stroke. These findings in men suggest that a high dietary folate intake may reduce the risk of cerebral infarction. C1 [Larsson, Susanna C.] Karolinska Inst, Div Nutr Epidemiol, Natl Inst Environm Med, SE-17177 Stockholm, Sweden. [Mannisto, Satu; Virtanen, Mikko J.; Kontto, Jukka; Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. [Albanes, Demetrius] NCI, NIH, Bethesda, MD 20892 USA. RP Larsson, SC (reprint author), Karolinska Inst, Div Nutr Epidemiol, Natl Inst Environm Med, POB 210, SE-17177 Stockholm, Sweden. EM susanna.larsson@ki.se RI Albanes, Demetrius/B-9749-2015; Larsson, Susanna/F-6065-2015; OI Larsson, Susanna/0000-0003-0118-0341; Mannisto, Satu/0000-0002-8668-3046; Kontto, Jukka/0000-0003-3899-9852 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; NCI NIH HHS [N01-CN-45165] NR 34 TC 20 Z9 20 U1 0 U2 1 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 APR 15 PY 2008 VL 167 IS 8 BP 954 EP 961 DI 10.1093/aje/kwm395 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286VU UT WOS:000254874900009 PM 18270369 ER PT J AU Lubin, JH Virtamo, J Weinstein, SJ Albanes, D AF Lubin, Jay H. Virtamo, Jarmo Weinstein, Stephanie J. Albanes, Demetrius TI Cigarette smoking and cancer: Intensity patterns in the alpha-tocopherol, beta-carotene cancer prevention study in Finnish men SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; Finland; models; statistical; smoking ID MODELING TOTAL EXPOSURE; LUNG-CANCER; BLADDER-CANCER; RISK; DNA; REPAIR; POLYMORPHISMS; ADDUCTS; SMOKERS; COHORT AB Relative risks for lung and bladder cancers by smoking intensity level off at more than 15-20 cigarettes per day. A three-parameter excess relative risk model in pack-years and intensity quantified this leveling (Lubin et al., Am J Epidemiol 2007;166:479-89). Above 15-20 cigarettes per day was an "inverse exposure rate" effect whereby, for equal pack-years, the excess relative risk/pack-year decreased with increasing intensity; that is, smoking at a lower intensity for a longer duration was more deleterious than smoking at a higher intensity for a shorter duration. After adjustment for pack-years, intensity effects were quantitatively homogeneous across multiple case-control studies of lung, bladder, oral cavity, pancreas, and esophagus cancers. The authors extended those analyses to examine intensity patterns for incident bladder, esophagus, kidney, larynx, liver, lung, oropharynx, and pancreas cancers by using data from a single prospective cohort in Finland, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, with follow-up from enrollment, which occurred between 1985 and 1988, through April 2004. At more than 10 cigarettes per day, they found an inverse exposure rate pattern for each cancer site. After adjustment for pack-years, intensity effects were quantitatively homogeneous across the diverse cancer sites and homogeneous with intensity effects from the prior analysis of multiple studies. Consistency of intensity patterns suggested a general phenomenon and may provide clues to the molecular basis of smoking-related cancer risk. C1 [Lubin, Jay H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. [Weinstein, Stephanie J.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Lubin, JH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. EM lubinj@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; NCI NIH HHS [N01-CN-45165] NR 22 TC 23 Z9 25 U1 0 U2 3 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 APR 15 PY 2008 VL 167 IS 8 BP 970 EP 975 DI 10.1093/aje/kwm392 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286VU UT WOS:000254874900011 PM 18250081 ER PT J AU Samanic, CM De Roos, AJ Stewart, PA Rajaraman, P Waters, MA Inskip, PD AF Samanic, Claudine M. De Roos, Anneclaire J. Stewart, Patricia A. Rajaraman, Preetha Waters, Martha A. Inskip, Peter D. TI Occupational exposure to pesticides and risk of adult brain tumors SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE central nervous system neoplasms; incidence; pesticides; United States ID CANCER MORTALITY; REPRODUCTIVE FACTORS; 2,4-DICHLOROPHENOXYACETIC ACID; UNITED-STATES; FOLLOW-UP; WORKERS; MANUFACTURE; MENINGIOMA; GLIOMA; APPLICATORS AB The authors examined incident glioma and meningioma risk associated with occupational exposure to insecticides and herbicides in a hospital-based, case-control study of brain cancer. Cases were 462 glioma and 195 meningioma patients diagnosed between 1994 and 1998 in three US hospitals. Controls were 765 patients admitted to the same hospitals for nonmalignant conditions. Occupational histories were collected during personal interviews. Exposure to pesticides was estimated by use of a questionnaire, combined with pesticide measurement data abstracted from published sources. Using logistic regression models, the authors found no association between insecticide and herbicide exposures and risk for glioma and meningioma. There was no association between glioma and exposure to insecticides or herbicides, in men or women. Women who reported ever using herbicides had a significantly increased risk for meningioma compared with women who never used herbicides (odds ratio = 2.4, 95% confidence interval: 1.4, 4.3), and there were significant trends of increasing risk with increasing years of herbicide exposure (p = 0.01) and increasing cumulative exposure (p = 0.01). There was no association between meningioma and herbicide or insecticide exposure among men. These findings highlight the need to go beyond job title to elucidate potential carcinogenic exposures within different occupations. C1 [Samanic, Claudine M.; Stewart, Patricia A.; Rajaraman, Preetha; Inskip, Peter D.] US Dept HHS, Div Canc Epidemiol & Genet, NCI, NIH, Rockville, MD 20852 USA. [De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [De Roos, Anneclaire J.] Univ Washington, Seattle, WA 98195 USA. [Waters, Martha A.] NIOSH, Cincinnati, OH 45226 USA. RP Samanic, CM (reprint author), US Dept HHS, Div Canc Epidemiol & Genet, NCI, NIH, 6120 Execut Blvd,Room 8003, Rockville, MD 20852 USA. EM samanicc@mail.nih.gov RI Waters, Martha/B-7441-2011 FU Intramural NIH HHS [ZIA CP010135-18]; NCI NIH HHS [N01-CP-15679-01] NR 46 TC 36 Z9 36 U1 1 U2 6 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 APR 15 PY 2008 VL 167 IS 8 BP 976 EP 985 DI 10.1093/aje/kwm401 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286VU UT WOS:000254874900012 PM 18299277 ER PT J AU Sharifi, N Farrar, WL AF Sharifi, Nima Farrar, William L. TI Re: "Body Size, Weight Cycling, and Risk of Renal Cell Carcinoma among Postmenopausal Women: The Women's Health Initiative (United States)" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID SLEEP-APNEA; OBESITY C1 [Sharifi, Nima] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Sharifi, Nima; Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Frederick, MD 21702 USA. [Sharifi, Nima; Farrar, William L.] NCI, Ctr Canc Res, Frederick, MD 21702 USA. RP Sharifi, N (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM galanthus7@yahoo.com NR 5 TC 1 Z9 1 U1 0 U2 0 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 APR 15 PY 2008 VL 167 IS 8 BP 1016 EP 1016 DI 10.1093/aje/kwn040 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286VU UT WOS:000254874900016 PM 18344511 ER PT J AU Nino, M Matos-Miranda, C Maeda, M Chen, L Allanson, J Armour, C Greene, C Kamaluddeen, M Rita, D Medne, L Zackai, E Mansour, S Superti-Furga, A Lewanda, A Bober, M Rosenbaum, K Braverman, N AF Nino, Michelle Matos-Miranda, Claudia Maeda, Momoe Chen, Li Allanson, Judith Armour, Christine Greene, Carol Kamaluddeen, Majeeda Rita, Debra Medne, Livija Zackai, Elaine Mansour, Sahar Superti-Furga, Andrea Lewanda, Amy Bober, Michael Rosenbaum, Kenneth Braverman, Nancy TI Clinical and molecular analysis of arylsulfatase E in patients with brachytelephalangic chondrodysplasia punctata SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE chondrodysplasia punctata; brachytelephalangic chondrodysplasia punctata; arylsulfatase E; CDPX1; mutation analysis; vitamin K deficiency; cervical vertebra abnormality; airway obstruction; X chromosome; Xp22.3 ID VITAMIN-K DEFICIENCY; MATRIX GLA PROTEIN; MATERNAL LUPUS-ERYTHEMATOSUS; LINKED RECESSIVE FORM; WARFARIN EMBRYOPATHY; PTS2 RECEPTOR; TRACHEOBRONCHIAL STENOSIS; KEUTEL-SYNDROME; HUMAN PEX7; MUTATIONS AB X-linked Recessive Chondrodysplasia Punctata (CDPX1) is due to a defect in arylsulfatase E (ARSE), located on Xp22.3. Neither the substrate nor function of the encoded warfarin-sensitive arylsulfatase has been identified and molecular analysis remains the only confirmatory diagnostic test. Nevertheless, the majority of patients evaluated have not had identifiable mutations in ARSE, and thus far 23 patients have been reported. The major clinical features in these patients are also present in a group now recognized as phenocopies, due to vitamin K deficiency in early gestation or maternal autoimmune disease. We evaluated the ARSE gene in 11 patients who met clinical criteria for CDPX1. We amplified all exons and intronic flanking sequence from each patient, and investigated suspected deletions or rearrangements by southern analysis. We identified mutations in seven individuals. Of the remainder, three had maternal conditions that further expand the phenocopy group. Thus, this group might represent a proportion of the mutation-negative patients in previous studies. We extracted clinical information from all prior reports over the past decade and show that there are few distinguishing features on examination between these two groups of patients. This study supports heterogeneity for CDPX1-like phenotypes and sorting these out will help to define the biological pathway and genetic contributors. (C) 2008 Wiley-Liss, Inc. C1 [Nino, Michelle] Johns Hopkins Bayview, NIDA, Baltimore, MD USA. [Matos-Miranda, Claudia; Maeda, Momoe; Chen, Li; Braverman, Nancy] Johns Hopkins Med Ctr, Inst Med Genet, Baltimore, MD USA. [Allanson, Judith; Armour, Christine] Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, CA USA. [Greene, Carol] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. [Kamaluddeen, Majeeda] Univ Calgary, Dept Pediat, Calgary, AB, Canada. [Rita, Debra] Lutheran Gen Hosp, Dept Genet, Park Ridge, IL USA. [Medne, Livija; Zackai, Elaine] Childrens Hosp, Div Genet, Philadelphia, PA 19104 USA. [Mansour, Sahar] St Georges NHS Trust, Reg Genet Dept, London, England. [Superti-Furga, Andrea] Univ Freiburg, Dept Pediat, D-7800 Freiburg, Germany. [Lewanda, Amy] Inova Fairfax Hosp Children, Dept Pediat, Falls Church, VA USA. [Bober, Michael] Alfred I duPont Hosp Children, Dept Pediat, Wilmington, DE USA. [Rosenbaum, Kenneth] Childrens Natl Med Ctr, Div Genet, Washington, DC 20010 USA. RP Braverman, N (reprint author), McGill Univ, Montreal Childrens Res Inst, 4060 SteCatherine W,PT406, Montreal, PQ H3Z 2Z3, Canada. EM nancy.braverman@mcgill.ca RI superti-furga, andrea/E-9162-2015; OI superti-furga, andrea/0000-0002-3543-7531; Bober, Michael/0000-0002-6178-1264 FU NICHD NIH HHS [HD024061, R01HD39747]; NIGMS NIH HHS [GM07471] NR 61 TC 22 Z9 22 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 APR 15 PY 2008 VL 146A IS 8 BP 997 EP 1008 DI 10.1002/ajmg.a.32159 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 282SO UT WOS:000254587700005 PM 18348268 ER PT J AU Johnson, RL Huang, W Jadhav, A Austin, CP Inglese, J Martinez, ED AF Johnson, Ronald L. Huang, Wenwei Jadhav, Ajit Austin, Christopher P. Inglese, James Martinez, Elisabeth D. TI A quantitative high-throughput screen identifies potential epigenetic modulators of gene expression SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE epigenetic; small molecule; GFP; HTS; HDAC; cell assay; cancer ID HISTONE DEACETYLASE INHIBITORS; MICROPLATE CYTOMETRY; CANCER-THERAPY; CELLS; ACETYLATION; SUPPRESSION; FAMILY; AGENTS; ASSAYS AB Epigenetic regulation of gene expression is essential in embryonic development and contributes to cancer pathology. We used a cell-based imaging assay that measures derepression of a silenced green fluorescent protein (GFP) reporter to identify novel classes of compounds involved in epigenetic regulation. This locus derepression (LDR) assay was screened against a 69,137-member chemical library using quantitative high-throughput screening (qHTS), a titration-response method that assays compounds at multiple concentrations. From structure-activity relationships of the 411 actives recovered from the qHTS, 6 distinct chemical series were chosen for further study. A total of 48 qHTS actives and analogs were counterscreened using the parental line of the LDR cells, which lack the GFP reporter. Three series-8-hydroxy quinoline, quinoline-8-thiol, and 1,3,5-thiadiazinane-2-thione-were not fluorescent and reconfirmed activity in the LDR cells. The three active series did not inhibit histone deacetylase activity in nuclear extracts or reactivate the expression of the densely methylated p16 gene in cancer cells. However, one series induced expression of the methylated CDH13 gene and inhibited the viability of several lung cancer lines at submicromolar concentrations. These results suggest that the identified small molecules act on epigenetic or transcriptional components and validate our approach of using a cell-based imaging assay in conjunction with qHTS. (c) 2007 Elsevier Inc. All rights reserved. C1 [Martinez, Elisabeth D.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. [Martinez, Elisabeth D.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. [Johnson, Ronald L.; Huang, Wenwei; Jadhav, Ajit; Austin, Christopher P.; Inglese, James] NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. RP Martinez, ED (reprint author), Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. EM elisabeth.martinez@utsouthwestern.edu FU Intramural NIH HHS; NCI NIH HHS [P50 CA070907-06, P50 CA070907, K22 CA118717-01, K22 CA118717-01A1, P50-CA70907, K22 CA118717] NR 35 TC 19 Z9 19 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 15 PY 2008 VL 375 IS 2 BP 237 EP 248 DI 10.1016/j.ab.2007.12.028 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 280FL UT WOS:000254410800010 PM 18211814 ER PT J AU McPhie, P AF McPhie, Peter TI Concentration-independent estimation of protein secondary structure by circular dichroism: a comparison of methods SO ANALYTICAL BIOCHEMISTRY LA English DT Editorial Material ID SPECTRA; POLYPEPTIDES; FILMS AB Estimation of a protein's secondary structure from its circular dichroism spectrum usually requires accurate knowledge of the concentration and pathlength of the sample. Two recently described methods avoid this problem by analysis of g-factor spectra (McPhie, Anal. Biochem. 293, 109-119) or scaling of relative intensities (Raussens et al., Anal. Biochem. 319, 114-121). Application of the two methods to the same samples shows that they can have similar efficacies. Calculation with the latter method is more rapid, but the performance of the former is maintained over reduced wavelength ranges. Published by Elsevier Inc. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP McPhie, P (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 215, Bethesda, MD 20892 USA. EM pmcphie@helix.nih.gov FU Intramural NIH HHS [Z01 DK024942-15] NR 10 TC 11 Z9 11 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 15 PY 2008 VL 375 IS 2 BP 379 EP 381 DI 10.1016/j.ab.2008.01.024 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 280FL UT WOS:000254410800031 PM 18294952 ER PT J AU Ward, MM Reveille, JD Learch, TJ Davis, JC Weisman, MH AF Ward, Michael M. Reveille, John D. Learch, Thomas J. Davis, John C., Jr. Weisman, Michael H. TI Impact of ankylosing spondylitis on work and family life: Comparisons with the US population SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS; FUNCTIONAL DISABILITY; GENERAL-POPULATION; MARITAL-STATUS; LABOR-FORCE; PROGRESSION; WITHDRAWAL; EMPLOYMENT; HISTORY AB Objective. To examine the impact of ankylosing spondylitis (AS) on work disability, nonparticipation in the labor force, marriage, divorce, and childbearing. Methods. In this cross-sectional survey, we asked AS patients (n = 591, 72.8% men, mean age 48.9 years) from the Los Angeles, Houston, San Francisco, and Washington, DC metropolitan areas about work and family life. The proportion of patients who were work disabled, did not participate in the labor force, had never been married, were divorced, or had a biological child were compared with the proportions expected for each outcome based on data from population surveys. Results. Patients with AS were more likely to be work disabled (13.3% versus 5.7%; P < 0.0001) and somewhat more likely to not participate in the labor force compared with the proportion expected (25.1% versus 21.8%; P = 0.07). These associations were stronger among patients age >= 45 years and those with AS for >= 20 years. AS patients were more likely than expected to have never been married (22.8% versus 15.4%; P < 0.0001) or to be divorced (13.2% versus 10.0%; P = 0.02). Women with AS were less likely than expected to have had children (54.7% versus 64.9%; P = 0.02), but the proportion of men with AS who had children was not different from that of the general population. Conclusion. Patients with AS in this study were more likely to have never been married, more likely to be divorced, and more than twice as likely to be work disabled than members of the general population. Women with AS were also less likely to have had children than women in the general population. C1 [Ward, Michael M.] NIAMS, NIH, Bethesda, MD 20892 USA. [Reveille, John D.] Univ Texas Houston, Ctr Hlth Sci, Houston, TX USA. [Learch, Thomas J.] Univ Calif Los Angeles, Keck Sch Med, Los Angeles, CA USA. [Davis, John C., Jr.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Ward, MM (reprint author), NIAMS, NIH, Bldg 10 Clin Dr,MSC 1468, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU Intramural NIH HHS; NCRR NIH HHS [M01-RR00425, M01-RR02558]; NIAMS NIH HHS [R01-AR048465] NR 29 TC 34 Z9 36 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2008 VL 59 IS 4 BP 497 EP 503 DI 10.1002/art.23523 PG 7 WC Rheumatology SC Rheumatology GA 288JT UT WOS:000254983400007 PM 18383414 ER PT J AU Liu, HY Liu, XD Jia, L Liu, YC Yang, HW Wang, GJ Xie, L AF Liu, Haiyan Liu, Xiaodong Jia, Lee Liu, Yuchun Yang, Huiwen Wang, Guangji Xie, Lin TI Insulin therapy restores impaired function and expression of P-glycoprotein in blood-brain barrier of experimental diabetes SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE blood-brain barrier; insulin; P-glycoprotein; diabetes mellitus; mdr1a/mdr1b mRNA ID RAT-BRAIN; ENDOTHELIAL-CELLS; IN-VIVO; CELLULAR PERMEABILITY; ADVANCED GLYCATION; MDR1B EXPRESSION; NITRIC-OXIDE; TRANSPORT; INDUCTION; BINDING AB We aimed to investigate effects of insulin on function and expression of P-glycoprotein (P-GP) in the blood-brain barrier of streptozotocin (STZ)-induced diabetic rats. Brain-to-plasma concentration ratio of vincristine (VCR) in rats was used as an indicator of in vivo function of P-GP. Western blot and quantitative real time-polymerase chain reaction were used to determine protein levels of P-GP and its mdr1a/mdr1b mRNA levels, respectively, in cerebral cortex of rats. In vitro effects of insulin on function and expression of P-GP in primarily cultured rat brain microvessel endothelial cells (rBMECs) were evaluated using rhodamine 123 (Rho123) uptakes and Western blot, respectively. The results showed that 3- and 5-week insulin treatment alleviated the impaired efflux function, expression and mdr1a/mdr1b mRNA levels of P-GP in cerebral cortex of diabetic rats. The 3- and 5-week insulin treatments also significantly enhanced P-GP levels and mdr1a/mdr1b mRNA levels in the cerebral cortex of normal rats. Addition of insulin to the insulin-deficient diabetic rat serum normalized the impaired function and expression of P-GP in rBMECs cultured in diabetic rat serum. When incubated with normal culture medium containing different levels of insulin, the rBMECs exhibited the enhanced P-GP levels and the reduced Rho123 uptake in a concentration-dependent manner. So we may conclude that appropriate level of insulin plays an important role in maintaining the normal function of BBB through regulating the function and expression of P-GP in the diabetic and normal rats. (c) 2008 Elsevier Inc. All rights reserved. C1 [Liu, Haiyan; Liu, Xiaodong; Liu, Yuchun; Yang, Huiwen; Wang, Guangji; Xie, Lin] China Pharmaceut Univ, Ctr Drug Metab & Pharmacokinet, Nanjing 210009, Peoples R China. [Jia, Lee] NCI, NIH, Toxicol & Pharmacol Branch, Dev Therapeut Program, Rockville, MD 20852 USA. RP Liu, XD (reprint author), China Pharmaceut Univ, Ctr Drug Metab & Pharmacokinet, Nanjing 210009, Peoples R China. EM xdliu@cpu.edu.cn NR 43 TC 36 Z9 43 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 15 PY 2008 VL 75 IS 8 BP 1649 EP 1658 DI 10.1016/j.bcp.2008.01.004 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 295KM UT WOS:000255473400009 PM 18299117 ER PT J AU Krystal, JH Carter, CS Geschwind, D Manji, HK March, JS Nestler, EJ Zubieta, JK Charney, DS Goldman, D Gur, RE Lieberman, JA Roy-Byrne, P Rubinow, DR Anderson, SA Barondes, S Berman, KF Blair, J Braff, DL Brown, ES Calabrese, JR Carlezon, WA Cook, EH Davidson, RJ Davis, M Desimone, R Drevets, WC Duman, RS Essock, SM Faraone, SV Freedman, R Friston, KJ Gelernter, J Geller, B Gill, M Gould, E Grace, AA Grillon, C Gueorguieva, R Hariri, AR Innis, RB Jones, EG Kleinman, JE Koob, GF Krystal, AD Leibenluft, E Levinson, DF Levitt, PR Lewis, DA Liberzon, I Lipska, BK Marder, SR Markou, A Mason, GF McDougle, CJ McEwen, BS McMahon, FJ Meaney, MJ Meltzer, HY Merikangas, KR Meyer-Lindenberg, A Mirnics, K Monteggia, LM Neumeister, A O'Brien, CP Owen, MJ Pine, DS Rapoport, JL Rauch, SL Robbins, TW Rosenbaum, JF Rosenberg, DR Ross, CA Rush, AJ Sackeim, HA Sanacora, G Schatzberg, AF Shaham, Y Siever, LJ Sunderland, T Tecott, LH Thase, ME Todd, RD Weissman, MM Yehuda, R Yoshikawa, T Young, EA McCandless, R AF Krystal, John H. Carter, Cameron S. Geschwind, Daniel Manji, Husseini K. March, John S. Nestler, Eric J. Zubieta, Jon-Kar Charney, Dennis S. Goldman, David Gur, Raquel E. Lieberman, Jeffrey A. Roy-Byrne, Peter Rubinow, David R. Anderson, Stewart A. Barondes, Samuel Berman, Karen F. Blair, James Braff, David L. Brown, E. Sherwood Calabrese, Joseph R. Carlezon, William A., Jr. Cook, Edwin H., Jr. Davidson, Richard J. Davis, Michael Desimone, Robert Drevets, Wayne C. Duman, Ronald S. Essock, Susan M. Faraone, Stephen V. Freedman, Robert Friston, Karl J. Gelernter, Joel Geller, Barbara Gill, Michael Gould, Elizabeth Grace, Anthony A. Grillon, Christian Gueorguieva, Ralitza Hariri, Ahmad R. Innis, Robert B. Jones, Edward G. Kleinman, Joel E. Koob, George F. Krystal, Andrew D. Leibenluft, Ellen Levinson, Douglas F. Levitt, Pat R. Lewis, David A. Liberzon, Israel Lipska, Barbara K. Marder, Stephen R. Markou, Athina Mason, Graeme F. McDougle, Christopher J. McEwen, Bruce S. McMahon, Francis J. Meaney, Michael J. Meltzer, Herbert Y. Merikangas, Kathleen R. Meyer-Lindenberg, Andreas Mirnics, Karoly Monteggia, Lisa M. Neumeister, Alexander O'Brien, Charles P. Owen, Michael J. Pine, Daniel S. Rapoport, Judith L. Rauch, Scott L. Robbins, Trevor W. Rosenbaum, Jerrold F. Rosenberg, David R. Ross, Christopher A. Rush, A. John Sackeim, Harold A. Sanacora, Gerard Schatzberg, Alan F. Shaham, Yavin Siever, Larry J. Sunderland, Trey Tecott, Laurence H. Thase, Michael E. Todd, Richard D. Weissman, Myrna M. Yehuda, Rachel Yoshikawa, Takeo Young, Elizabeth A. McCandless, R. TI It is time to take a stand for medical research and against terrorism targeting medical scientists SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 [Krystal, John H.; Duman, Ronald S.; Gelernter, Joel; Mason, Graeme F.; Neumeister, Alexander; Sanacora, Gerard] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Krystal, John H.; Duman, Ronald S.; Gelernter, Joel; Mason, Graeme F.; Neumeister, Alexander; Sanacora, Gerard] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. [Duman, Ronald S.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT USA. [Duman, Ronald S.] Yale Univ, Sch Med, Interdept Neurosci Program, New Haven, CT USA. [Gelernter, Joel] VA Connecticut Hlthcare Syst, West Haven, CT USA. [Nestler, Eric J.; Brown, E. Sherwood; Monteggia, Lisa M.; Rush, A. John; McCandless, R.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Nestler, Eric J.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Braff, David L.; Markou, Athina] Univ Calif San Diego, Dept Psychiat, Sch Med, San Diego, CA 92103 USA. [Braff, David L.; Markou, Athina] Univ Calif San Diego, Sch Med, Dept Psychiat, San Diego, CA 92103 USA. [Carter, Cameron S.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. [Carter, Cameron S.] Univ Calif Davis, Dept Psychiat, Davis, CA 95616 USA. [Jones, Edward G.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. [Geschwind, Daniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Geschwind, Daniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Marder, Stephen R.] 22 Mental Illness Res Educ & Clin Ctr, VA Vet Integrated Serv Networks, Los Angeles, CA USA. [Barondes, Samuel] Univ Calif San Francisco, Ctr Neurobiol & Psychiat, Langley Porter Psychiat Inst, San Francisco, CA 94143 USA. [Tecott, Laurence H.] Univ Calif San Francisco, Ctr Neurobiol & Psychiat, Dept Psychiat, San Francisco, CA 94143 USA. [Levinson, Douglas F.] Stanford Univ, Sch Med, Dept Psychiat, Palo Alto, CA 94304 USA. [Schatzberg, Alan F.] Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, Stanford, CA 94304 USA. [Grace, Anthony A.; Hariri, Ahmad R.; Lewis, David A.; Thase, Michael E.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Grace, Anthony A.; Lewis, David A.] Univ Pittsburgh, Sch Med, Dept Neurosci, Pittsburgh, PA USA. [Grace, Anthony A.] Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA USA. [Hariri, Ahmad R.] Univ Pittsburgh, Sch Med, Ctr Neural Basis Cognit, Pittsburgh, PA USA. [O'Brien, Charles P.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Gur, Raquel E.] Univ Penn, Sch Med, Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. [Gur, Raquel E.] Univ Penn, Sch Med, Med Ctr, Dept Neurol, Philadelphia, PA 19104 USA. [Gur, Raquel E.] Univ Penn, Sch Med, Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. [O'Brien, Charles P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Manji, Husseini K.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Lab Mol Pathophysiol & Exp, Bethesda, MD 20892 USA. [McMahon, Francis J.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Genet Basis Mood & Anxiety, Bethesda, MD 20892 USA. [Grillon, Christian] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Unit Affect Psychophysiol, Bethesda, MD 20892 USA. [Leibenluft, Ellen] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Unit Affect Disorders, Bethesda, MD 20892 USA. [Blair, James] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Unit Affect Cognit Neurosc, Bethesda, MD 20892 USA. [Pine, Daniel S.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Sect Dev & Affect Neurosc, Bethesda, MD 20892 USA. [Drevets, Wayne C.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Sect Neuroimaging, Bethesda, MD 20892 USA. [Kleinman, Joel E.; Lipska, Barbara K.] NIMH, NIH, Dept Hlth & Human Serv,Sect Neuropathol, Intramural Res Program,Mood & Anxiety Disorders P, Bethesda, MD 20892 USA. [Berman, Karen F.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. [Shaham, Yavin] NIMH, NIH, Dept Hlth & Human Serv,Behav Neurosci Branch, Intramural Res Program,Clin Brain Disorders Branc, Bethesda, MD 20892 USA. [Innis, Robert B.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Mol Imaging Branch, Bethesda, MD 20892 USA. [Rapoport, Judith L.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Child Psychiat Branch, Bethesda, MD 20892 USA. [Rubinow, David R.] NIMH, NIH, Dept Hlth & Human Serv, Intramural Res Program,Behav Endocrinol Branch, Bethesda, MD 20892 USA. [Goldman, David] NIAAA, NIH, Neurogenet Lab, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Behav Sci, Baltimore, MD 21205 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Rosenbaum, Jerrold F.] Massachusetts Gen Hosp, Dept Psychiat, Belmont, MA USA. [Carlezon, William A., Jr.] McLean Hosp, Mailman Res Ctr, Belmont, MA 02178 USA. [Carlezon, William A., Jr.; Rauch, Scott L.; Rosenbaum, Jerrold F.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Desimone, Robert] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Rubinow, David R.] Emory Univ, Dept Psychiat, Yerkes Natl Primate Ctr, Atlanta, GA 30322 USA. Univ N Carolina, Dept Psychiat & Behav Sci, Chapel Hill, NC USA. [March, John S.; Krystal, Andrew D.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Zubieta, Jon-Kar; Young, Elizabeth A.] Univ Michigan, Dept Psychiat, Med Ctr, Ann Arbor, MI 48109 USA. [Zubieta, Jon-Kar; Liberzon, Israel; Young, Elizabeth A.] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Rosenberg, David R.] Wayne State Univ, Sch Med, Dept Psychiat, Detroit, MI USA. [McDougle, Christopher J.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Inst Juvenille Res, Chicago, IL 60612 USA. [Davidson, Richard J.] Univ Wisconsin, WM Key Lab Funct Brain Imaging & Behav, Madison, WI USA. [Sackeim, Harold A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Sackeim, Harold A.] Columbia Univ, Mailman Sch Publ Hlth, Dept Radiol, Coll Phys & Surg, New York, NY 10027 USA. [Weissman, Myrna M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. [Charney, Dennis S.; Siever, Larry J.; Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Charney, Dennis S.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Charney, Dennis S.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. [McEwen, Bruce S.] Rockefeller Univ, Harold & Margaret Milliken Hatch Lab Neuroendocri, Neuroendocrinol Lab, New York, NY 10021 USA. [Siever, Larry J.; Yehuda, Rachel] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY USA. [Freedman, Robert] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Boulder, CO 80309 USA. [Freedman, Robert] Denver VA Med Ctr, MIRECC, VISN19, Denver, CO USA. [Meltzer, Herbert Y.; Mirnics, Karoly] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. [Levitt, Pat R.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA. [Levitt, Pat R.] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN USA. [Roy-Byrne, Peter] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Roy-Byrne, Peter] Harborview Med Ctr, Harborview Ctr Hlthcare Improvement Addict, Seattle, WA USA. [Geller, Barbara; Todd, Richard D.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Calabrese, Joseph R.] Case Western Reserve Univ, Sch Med, Univ Hosp Case Med Ctr,Dept Psychiat, Bipolar Disorder Res Ctr,Mood Disorders Program, Cleveland, Qld, Australia. [Gould, Elizabeth] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. [Meaney, Michael J.] McGill Univ, Dept Psychiat, Montreal Neurol Inst, Montreal, PQ, Canada. [Meaney, Michael J.] McGill Univ, Doughlas Hosp Res Ctr, Ctr Studies Humnan Stress, Montreal, PQ, Canada. [Gill, Michael] Univ Dublin Trinity Coll, Inst Mol Med, Dublin 2, Ireland. [Gill, Michael] Univ Dublin Trinity Coll, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 2, Ireland. [Yoshikawa, Takeo] RIKEN, Brain Sci Inst, Lab Mol Psychiat, Wako, Saitama, Japan. [Friston, Karl J.] UCL, Inst Neurol, Wellcome Trust Ctr Neuroimaging, London WC1E 6BT, England. [Robbins, Trevor W.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 1TN, England. [Owen, Michael J.] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, Wales. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, Dept Psychiat, D-6800 Mannheim, Germany. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, Dept Psychotherapy, D-6800 Mannheim, Germany. RP Krystal, JH (reprint author), VA Connecticut Hlth Syst, Psychiat Serv 116 A, 950 Campbell Ave, West Haven, CT 06516 USA. EM john.krystal@yale.edu RI McMahon, Francis/A-7290-2009; Friston, Karl/D-9230-2011; turton, miranda/F-4682-2011; Hariri, Ahmad/D-5761-2011; Mirnics, Karoly/E-6730-2010; Krystal, Andrew/J-7109-2013; shaham, yavin/G-1306-2014; Lewis, David/G-4053-2014; Meltzer, Herbert/E-8131-2013; Goldman, David/F-9772-2010; koob, george/P-8791-2016; Meyer-Lindenberg, Andreas/H-1076-2011; OI Friston, Karl/0000-0001-7984-8909; Mirnics, Karoly/0000-0002-5521-0254; Krystal, Andrew/0000-0002-6702-781X; Lewis, David/0000-0002-3225-6778; Goldman, David/0000-0002-1724-5405; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Gill, Michael/0000-0003-0206-5337; Rush, Augustus/0000-0003-2004-2382; Weissman, Myrna/0000-0003-3490-3075; McMahon, Francis/0000-0002-9469-305X; Gueorguieva, Ralitza/0000-0003-0944-5973; Faraone, Stephen/0000-0002-9217-3982 FU Medical Research Council [G0001354] NR 3 TC 6 Z9 6 U1 0 U2 9 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 APR 15 PY 2008 VL 63 IS 8 BP 725 EP 727 DI 10.1016/j.biopsych.2008.03-005 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 286AJ UT WOS:000254817100001 PM 18371494 ER PT J AU Xu, H Baidoo, KE Wong, KJ Brechbiel, MW AF Xu, Heng Baidoo, Kwamena E. Wong, Karen J. Brechbiel, Martin W. TI A novel bifunctional maleimido CHX-A '' chelator for conjugation to thiol-containing biomolecules SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE monoclonal antibody; thiol-maleimide chemistry; imaging and/or therapies of cancer ID DISSEMINATED PERITONEAL DISEASE; IN-VIVO; DIETHYLENETRIAMINEPENTAACETIC ACID; MONOCLONAL-ANTIBODIES; SULFHYDRYL-GROUPS; CANCER-THERAPY; DTPA; AGENT; DERIVATIVES; RADIATION AB A novel bifunctional maleimido CHX-A '' DTPA chelator 5 was developed and conjugated to the monoclonal antibody trastuzumab (Herceptin) and subsequently radiolabeled with In-111. The resulting In-111 labeled immunoconjugate 2 was demonstrated to bind to SKOV-3 ovarian cancer cells comparably to an isothiocyanato CHX-A '' DTPA modified native trastuzumab, 1. Through efficient thiol-maleimide chemistry, antibodies, peptides or other targeting vectors can now be modified with an established radioactive metal chelating agent CHX-A '' DTPA for imaging and/or therapies of cancer. Published by Elsevier Ltd. C1 [Xu, Heng; Baidoo, Kwamena E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Wong, Karen J.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room 1B40,10 Ctr Dr, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov FU Intramural NIH HHS [Z01 SC006353-24, Z01 SC006353-25, Z01 SC010051-11, Z01 SC010051-12] NR 21 TC 10 Z9 10 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 15 PY 2008 VL 18 IS 8 BP 2679 EP 2683 DI 10.1016/j.bmcl.2008.03.022 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 292DJ UT WOS:000255246400032 PM 18359632 ER PT J AU Klauda, JB Roberts, MF Redfield, AG Brooks, BR Pastor, RW AF Klauda, Jeffery B. Roberts, Mary F. Redfield, Alfred G. Brooks, Bernard R. Pastor, Richard W. TI Rotation of lipids in membranes: Molecular dynamics simulation, P-31 spin-lattice relaxation, and rigid-body dynamics SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; SYMMETRIC TOP MACROMOLECULES; FIELD-CYCLING NMR; HEAD-GROUP; FLUORESCENCE DEPOLARIZATION; LIQUID/LIQUID INTERFACES; COMPUTER-SIMULATION; CIRCULAR-CYLINDERS; BILAYER; SURFACE AB Molecular dynamics simulations and P-31-NMR spin-lattice (R-1) relaxation rates from 0.022 to 21.1 T of fluid phase dipalmitoylphosphatidylcholine bilayers are compared. Agreement between experiment and direct prediction from simulation indicates that the dominant slow relaxation (correlation) times of the dipolar and chemical shift anisotropy spin-lattice relaxation are similar to 10 ns and 3 ns, respectively. Overall reorientation of the lipid body, consisting of the phosphorus, glycerol, anclacyl chains, is well described within a rigid-body model. Wobble, with D-perpendicular to = 1-2 X 10(8) s(-1), is the primary component of the 10 ns relaxation; this timescale is consistent with the tumbling of a lipid-sized cylinder in a medium with the viscosity of liquid hexadecane. The value for D parallel to, the diffusion constant for rotation about the long axis of the lipid body, is difficult to determine precisely because of averaging by fast motions and wobble; it is tentatively estimated to be 1 X 10(7)s(-1). The resulting D-parallel to/D-perpendicular to approximate to 0. 1 implies that axial rotation is strongly modulated by interactions at the lipid/water interface. Rigid-body modeling and potential of mean force evaluations show that the choline group is relatively uncoupled from the rest of the lipid. This is consistent with the ratio of chemical shift anisotropy and dipolar correlation times reported here and the previous observations that P-31-NMR lineshapes are axially symmetric even in the gel phase of dipalmitoylphosphatidylcholine. C1 NIH, NHLBI, Lab Comput Biol, Bethesda, MD 20892 USA. Boston Coll, Dept Chem, Chestnut Hill, MA 02467 USA. Brandeis Univ, Dept Biochem, Waltham, MA USA. RP Pastor, RW (reprint author), NIH, NHLBI, Lab Comput Biol, Bethesda, MD 20892 USA. EM pastorr@nhlbi.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM077974, GM 077974] NR 40 TC 50 Z9 50 U1 3 U2 20 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR 15 PY 2008 VL 94 IS 8 BP 3074 EP 3083 DI 10.1529/biophysj.107.121806 PG 10 WC Biophysics SC Biophysics GA 280IP UT WOS:000254420100016 PM 18192349 ER PT J AU Schultz, ZD Levin, IW AF Schultz, Zachary D. Levin, Ira W. TI Lipid Microdomain formation: Characterization by infrared spectroscopy and ultrasonic velocimetry SO BIOPHYSICAL JOURNAL LA English DT Article ID MODULATE CHANNEL FUNCTION; BOVINE DIGESTIVE-TRACT; GPI-ANCHORED PROTEINS; MASS-SPECTROMETRY; TERNARY MIXTURES; MEMBRANE DOMAINS; MODEL MEMBRANES; DIFFERENT PARTS; CELL-MEMBRANES; RAFT FORMATION AB We demonstrate the use of vibrational infrared spectroscopy applied to characterize lipid microdomain sizes derived from a model raft-like system consisting of nonhydroxy galactocerebroside, cholesterol, and dipalmitoylphosphatidylcholine components. The resulting spectroscopic correlation field components of the lipid acyl chain CH2 methylene deformation modes, observed when lipid multilamellar assemblies are rapidly frozen from the liquid crystalline state to the gel phase, indicate the existence of lipid microdomains on a scale of several nanometers. The addition of cholesterol disrupts the glycosphingolipid selectively but perturbs the di-saturated chain phospholipid matrix. Complementary acoustic velocimetry measurements indicate that the microdomain formation decreases the total volume adiabatic compressibilities of the multilamellar vesicle assemblies. The addition of cholesterol, however, disrupts the galactocerebroside domains, resulting in a slight increase in the lipid assemblies' total adiabatic compressibility. The combination of these two physical approaches offers new insight into microdomain formation and their properties in model bilayer systems. C1 [Schultz, Zachary D.; Levin, Ira W.] Natl Inst Hlth, Natl Inst Diab & Digestive & Kidney Dis, Phys Chem Lab, Bethesda, MD 20892 USA. RP Levin, IW (reprint author), Natl Inst Hlth, Natl Inst Diab & Digestive & Kidney Dis, Phys Chem Lab, Bethesda, MD 20892 USA. EM iwl@helix.nih.gov RI Schultz, Zachary/L-5724-2013 OI Schultz, Zachary/0000-0003-1741-8801 FU Intramural NIH HHS NR 57 TC 13 Z9 13 U1 0 U2 7 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR 15 PY 2008 VL 94 IS 8 BP 3104 EP 3114 DI 10.1529/biophysj.107.119735 PG 11 WC Biophysics SC Biophysics GA 280IP UT WOS:000254420100019 PM 18192352 ER PT J AU Mueller, F Wach, P McNally, JG AF Mueller, Florian Wach, Paul McNally, James G. TI Evidence for a common mode of transcription factor interaction with chromatin as revealed by improved quantitative fluorescence recovery after photobleaching SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEAR PROTEINS; IN-VIVO; FRAP ANALYSIS; LIVING CELLS; BINDING; DIFFUSION; DNA; KINETICS; MOBILITY; DYNAMICS AB How site-specific transcription factors scan the genome to locate their target sites is a fundamental question in gene regulation. The in vivo binding interactions of several different transcription factors with chromatin have been investigated recently using quantitative fluorescence recovery after photobleaching (FRAP). These analyses have yielded significantly different estimates of both the binding rates and the number of predicted binding states of the respective transcription factors. We show here that these discrepancies are not due to fundamental differences among the site-specific transcription factors, but rather arise from errors in FRAP modeling. The two principal errors are a neglect of diffusion's role and an oversimplified approximation of the photobleach profile. Accounting for these errors by developing a revised FRAP protocol eliminates most of the previous discrepancies in the binding estimates for the three different transcription factors analyzed here. The new estimates predict that for each of the three transcription factors, similar to 75% of the molecules are freely diffusing within the nucleus, whereas the remainder is bound with an average residence time of similar to 2.5 s to a single type of chromatin binding site. Such consistent predictions for three different molecules suggest that many site-specific transcription factors may exhibit similar in vivo interactions with native chromatin. C1 [Mueller, Florian; McNally, James G.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. [Wach, Paul] Graz Univ Technol, Inst Med Engn, A-8010 Graz, Austria. [Mueller, Florian] Graz Univ Technol, Inst Genom & Bioinformat, A-8010 Graz, Austria. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. EM mcnallyj@exchange.nih.gov RI Mueller, Florian/C-9075-2012 OI Mueller, Florian/0000-0002-9622-4396 FU Intramural NIH HHS NR 29 TC 95 Z9 95 U1 0 U2 5 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR 15 PY 2008 VL 94 IS 8 BP 3323 EP 3339 DI 10.1529/biophysj.107.123182 PG 17 WC Biophysics SC Biophysics GA 280IP UT WOS:000254420100040 PM 18199661 ER PT J AU Jaluria, P Konstantopoulos, K Betenbaugh, M Shiloach, J AF Jaluria, Pratik Konstantopoulos, Konstantinos Betenbaugh, Michael Shiloach, Joseph TI Egr1 and Gas6 facilitate the adaptation of HEK-293 cells to serum-free media by conferring enhanced viability and higher growth rates SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE microarrays; adaptation; serum-free media; early growth response 1; growth arrest specific 6; survivability ID VASCULAR SMOOTH-MUSCLE; K-DEPENDENT GAS6; MAMMALIAN-CELLS; PROTEIN-S; CULTURE INSULTS; PROSTATE-CANCER; MICROARRAY DATA; AXL RECEPTOR; HT1080 CELLS; DNA-DAMAGE AB Animal-derived serum is an essential media supplement for mammalian cells in cell culture. For a number of reasons including cost, regulatory concerns, lot inconsistency, potential contamination with adventitious agents, and down-stream processing it is desirable to eliminate the use of serum. Existing protocols designed to adapt cells to serum-free media (SFM) are time-consuming and provide little insight into how the cells adapt. To better understand the physiological responses associated with serum withdrawal and to expedite the adaptation process, a Human Embryonic Kidney-293 (HEK-293) cell line was propagated in 10% fetal bovine serum (FBS) and was progressively adapted to SFM and analyzed at specific serum levels by oligonucleotide microarrays. Of the differentially expressed genes two, early growth response 1 (egr1) and growth arrest specific 6 (gas6), were selected for further analysis based on their level of differential expression, overall expression patterns, and proposed functionalities. HEK-293 cells, propagated in 10% FBS were transfected with egr1 or gas6 and then adapted to SFM. Results indicated that higher expression of either gene moderately enhanced the ability of both cell lines to adapt to SFM. Egr1 appeared to have a greater impact on adaptability than gas6. Results also indicated that specific protein production was unaltered when the expression of egr1 was increased. Flow cytometric analysis revealed increased expression of egr1 was associated with an increase in the percentage of cells in the G2/M phases. These results indicate that enhanced expression of egr1 or gas6 facilitate adaptation to SFM by improving growth and viability. C1 [Jaluria, Pratik; Shiloach, Joseph] NIDDKD, NIH, Biotechnol Unit, Bethesda, MD 20892 USA. [Jaluria, Pratik; Konstantopoulos, Konstantinos; Betenbaugh, Michael] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA. RP Shiloach, J (reprint author), NIDDKD, NIH, Biotechnol Unit, 9000 Rockville Pike,Bldg 14A,Room 173, Bethesda, MD 20892 USA. EM ljs@helix.nih.gov RI Konstantopoulos, Konstantinos/A-7045-2011; Betenbaugh, Michael J./A-3252-2010 OI Betenbaugh, Michael J./0000-0002-6336-4659 FU Intramural NIH HHS; NIAMS NIH HHS [R01 AR053358] NR 54 TC 7 Z9 7 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD APR 15 PY 2008 VL 99 IS 6 BP 1443 EP 1452 DI 10.1002/bit.21707 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 277KQ UT WOS:000254211700017 PM 18023050 ER PT J AU Little, RF AF Little, Richard F. TI AIDS, T cells, chemotherapy: HAART-breaking? SO BLOOD LA English DT Editorial Material ID LYMPHOMA AB Chemotherapy depletes T cells in AIDS patients on HAART, but preexisting lymphopenia limits the scale compared with non-AIDS patients. Thus T-cell recovery time to baseline may be rapid, but the risk of additional AIDS-related complications persists. C1 Natl Canc Inst, Bethesda, MD USA. RP Little, RF (reprint author), Natl Canc Inst, Bethesda, MD USA. NR 3 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 APR 15 PY 2008 VL 111 IS 8 BP 3921 EP 3922 DI 10.1182/blood-2008-01-134528 PG 2 WC Hematology SC Hematology GA 290PM UT WOS:000255134700012 PM 18434970 ER PT J AU Bluhm, EC Ronckers, C Hayashi, RJ Neglia, JP Mertens, AC Stovall, M Meadows, AT Mitby, PA Whitton, JA Hammond, S Barker, JD Donaldson, SS Robison, LL Inskip, PD AF Bluhm, Elizabeth C. Ronckers, Ckile Hayashi, Robert J. Neglia, Joseph P. Mertens, Ann C. Stovall, Marilyn Meadows, Anna T. Mitby, Pauline A. Whitton, John A. Hammond, Sue Barker, Joseph D. Donaldson, Sarah S. Robison, Leslie L. Inskip, Peter D. TI Cause-specific mortality and second cancer incidence after non-Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study SO BLOOD LA English DT Article ID LONG-TERM SURVIVORS; MALIGNANT NEOPLASMS; 5-YEAR SURVIVORS; ADOLESCENT CANCER; RADIATION-THERAPY; NORDIC COUNTRIES; RISK; LEUKEMIA; DISEASE; COHORT AB Second primary malignancies and premature death are a concern for patients surviving treatment for childhood lymphomas. We assessed mortality and second malignant neoplasms (SMNs) among 1082 5-year survivors of non-Hodgkin lymphoma (NHL) in the Childhood Cancer Survivor Study, a multi-institutional North American retrospective cohort study of cancer survivors diagnosed from 1970 to 1986. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated using US population rates. Relative risks for death and solid tumor SMNs were calculated based on demographic, clinical, and treatment characteristics using Poisson regression models. There were 87 observed deaths (SMR = 4.2; 95% CI, 1.8-4.1) with elevated rates of death from solid tumors, leukemia, cardiac disease, and pneumonia. Risk for death remained elevated beyond 20 years after NHL. Risk factors for death from causes other than NHL included female sex (rate ratio [RR] = 3.4) and cardiac radiation therapy exposure (RR = 1.9). There were 27 solid tumor SMNs (SIR = 3.9; 95% CI, 2.6-5.7) with 3% cumulative incidence between 5 and 20 years after NHL diagnosis. Risk factors were female sex (RR = 3.11), mediastinal NHL disease (RR = 5.2), and breast irradiation (RR = 4.3). Survivors of childhood NHL, particularly those treated with chest RT, are at continued increased risk of early mortality and solid tumor SMNs. C1 [Bluhm, Elizabeth C.; Ronckers, Ckile; Inskip, Peter D.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. [Ronckers, Ckile] Emma Childrens Hosp, Acad Med Ctr, Dept Pediat Oncol, Amsterdam, Netherlands. [Hayashi, Robert J.] Washington Univ, Sch Med, Div Pediat Hematol & Oncol, St Louis, MO USA. [Neglia, Joseph P.; Mitby, Pauline A.] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. [Mertens, Ann C.] Aflac Canc Ctr & Blood Disorders Serv, Emory Childrens Ctr, Atlanta, GA USA. [Stovall, Marilyn] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Meadows, Anna T.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Whitton, John A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hammond, Sue] Ohio State Univ, Sch Med, Dept Pathol, Columbus, OH 43210 USA. [Barker, Joseph D.] IMS Management Syst, Silver Spring, MD USA. [Donaldson, Sarah S.] Stanford Univ, Med Ctr, Dept Radiat Oncol, Stanford, CA 94305 USA. [Robison, Leslie L.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. RP Bluhm, EC (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7238, Rockville, MD 20892 USA. EM bluhme@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [U24 CA055727, U24 CA55727] NR 44 TC 29 Z9 29 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 APR 15 PY 2008 VL 111 IS 8 BP 4014 EP 4021 DI 10.1182/blood-2007-08-106021 PG 8 WC Hematology SC Hematology GA 290PM UT WOS:000255134700022 PM 18258798 ER PT J AU Smedby, KE Vajdic, CM Falster, M Engels, EA Martinez-Maza, O Turner, J Hjalgrim, H Vineis, P Costantini, AS Bracci, PM Holly, EA Willett, E Spinelli, JJ La Vecchia, C Zheng, TZ Becker, N De Sanjose, S Chiu, BCH Dal Maso, L Cocco, P Maynadie, M Foretova, L Staines, A Brennan, P Davis, S Severson, R Cerhan, JR Breen, EC Birmann, B Grulich, AE Cozen, W AF Smedby, Karin Ekstrom Vajdic, Claire M. Falster, Michael Engels, Eric A. Martinez-Maza, Otoniel Turner, Jennifer Hjalgrim, Henrik Vineis, Paolo Costantini, Adele Seniori Bracci, Paige M. Holly, Elizabeth A. Willett, Eleanor Spinelli, John J. La Vecchia, Carlo Zheng, Tongzhang Becker, Nikolaus De Sanjose, Silvia Chiu, Brian C. -H. Dal Maso, Luigino Cocco, Pierluigi Maynadie, Marc Foretova, Lenka Staines, Anthony Brennan, Paul Davis, Scott Severson, Richard Cerhan, James R. Breen, Elizabeth C. Birmann, Brenda Grulich, Andrew E. Cozen, Wendy TI Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph consortium SO BLOOD LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; POPULATION-BASED COHORT; INFLAMMATORY-BOWEL-DISEASE; PRIMARY SJOGRENS-SYNDROME; T-CELL LYMPHOMA; CELIAC-DISEASE; CANCER INCIDENCE; MEDICAL HISTORY; RHEUMATOID-ARTHRITIS; HEMATOPOIETIC CANCER AB Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model. Sjogren syndrome was associated with a 6.5-fold increased risk of NHL, a 1000-fold increased risk of parotid gland marginal zone lymphoma (OR = 996; 95% CI, 216-4596), and with diffuse large B-cell and follicular lymphomas. Systemic lupus erythematosus was associated with a 2.7-fold increased risk of NHL and with diffuse large B-cell and marginal zone lymphomas. Hemolytic anemia was associated with diffuse large B-cell NHL. T-cell NHL risk was increased for patients with celiac disease and psoriasis. Results for rheumatoid arthritis were heterogeneous between studies. Inflammatory bowel disorders, type 1 diabetes, sarcoidosis, pernicious anemia, and multiple sclerosis were not associated with risk of NHL or subtypes. Thus, specific autoimmune disorders are associated with NHL risk beyond the development of rare NHL subtypes in affected organs. The pattern of associations with NHL subtypes may harbor clues to lymphomagenesis. C1 [Smedby, Karin Ekstrom] Karolinska Univ Hosp, Dept Med, Clin Epidemiol Unit, SE-17176 Stockholm, Sweden. [Vajdic, Claire M.; Falster, Michael; Grulich, Andrew E.] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. [Engels, Eric A.] NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Natl Inst Hlth, Rockville, MD USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, David Geffen Sch Med, Los Angeles, CA USA. [Turner, Jennifer] St Vincents Hosp, Dept Anat Pathol, Sydney, NSW 2010, Australia. [Hjalgrim, Henrik] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, London, England. [Costantini, Adele Seniori] Ist Sci Reg Toscana, Epidemiol Unit, Ctr Study & Prevent Canc, Florence, Italy. [Bracci, Paige M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Holly, Elizabeth A.] Univ York, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England. [Spinelli, John J.] BC Canc Agcy, Canc Control Res Program, Vancouver, BC, Canada. [La Vecchia, Carlo] Univ Milan, Ist Ric Farmacol Mario Negri, Milan, Italy. [La Vecchia, Carlo] Univ Milan, Ist Stat Med & Biometria, Milan, Italy. [Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Becker, Nikolaus] German Canc Res Ctr, Div Clin Epidemiol, D-6900 Heidelberg, Germany. [De Sanjose, Silvia] Inst Catala Oncol, Epidemiol Registre Canc, Barcelona, Spain. [Chiu, Brian C. -H.] Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. [Dal Maso, Luigino] Aviano Canc Ctr, Epidemiol & Biostat Unit, I-33081 Aviano, Italy. [Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Cagliari, Italy. [Maynadie, Marc] Registry Hematol Malignancies Cote Or, Dijon, France. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Staines, Anthony] Dublin City Univ, Sch Nursing, Dublin 9, Ireland. [Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Davis, Scott] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Davis, Scott] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. [Severson, Richard] Wayne State Univ, Dept Family Med, Sch Med, Detroit, MI USA. [Severson, Richard] Wayne State Univ, Jarmanos Canc Inst, Sch Med, Detroit, MI USA. [Cerhan, James R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Breen, Elizabeth C.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Birmann, Brenda] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Birmann, Brenda] Harvard Univ, Sch Med, Boston, MA USA. [Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. RP Smedby, KE (reprint author), Karolinska Univ Hosp, Dept Med, Clin Epidemiol Unit, SE-17176 Stockholm, Sweden. EM karin.ekstrom.smedby@ki.se RI Kane, Eleanor/B-4349-2009; Martinez-Maza, Otoniel/B-2667-2009; Spinelli, John/B-6210-2013; de Sanjose Llongueras, Silvia/H-6339-2014; OI dal maso, luigino/0000-0001-6163-200X; La Vecchia, Carlo/0000-0003-1441-897X; Martinez-Maza, Otoniel/0000-0003-1364-0675; Falster, Michael/0000-0001-6444-7272; Vajdic, Claire/0000-0002-3612-8298; Cerhan, James/0000-0002-7482-178X; Staines, Anthony/0000-0001-9161-1357 FU NCI NIH HHS [PC67008, CA104682, CA87014, CA89745, K07 CA115687, N01 PC065064, N01 PC067008, N01 PC067009, N01 PC067010, PC65064, PC67009, PC67010, PC71105, R01 CA045614, R01 CA051086, R01 CA062006, R01 CA087014, R01 CA104682, R03 CA089745] NR 53 TC 140 Z9 151 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD APR 15 PY 2008 VL 111 IS 8 BP 4029 EP 4038 DI 10.1182/blood-2007-10-119974 PG 10 WC Hematology SC Hematology GA 290PM UT WOS:000255134700024 PM 18263783 ER PT J AU Narazaki, M Segarra, M Tosato, G AF Narazaki, Masashi Segarra, Marta Tosato, Giovanna TI Sulfated polysaccharides identified as inducers of neuropilin-1 internalization and functional inhibition of VEGF165 and semaphorin3A SO BLOOD LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; LOW-DENSITY-LIPOPROTEIN; SCAVENGER RECEPTOR; TUMOR ANGIOGENESIS; AXON GUIDANCE; IN-VIVO; CELLS; BINDING; VEGF(165); MACROPHAGE AB Neuropilin-1 (NRP1) and NRP2 are cell surface receptors shared by class 3 semaphorins and vascular endothelial growth factor (VEGF). Ligand interaction with NRPs selects the specific signal transducer, plexins for semaphorins or VEGF receptors for VEGF, and promotes NIRP internalization, which effectively shuts down receptor-mediated signaling by a second ligand. Here, we show that the sulfated polysaccharides dextran sulfate and fucoidan, but not others, reduce endothelial cell-surface levels of NRP1, NRP2, and to a lesser extent VEGFR-1 and VEGFR-2, and block the binding and in vitro function of semaphorin3A and VEGF(165). Administration of fucoidan to mice reduces VEGF(165)-induced angiogenesis and tumor neovascularization in vivo. We find that dextran sulfate and fucoidan can bridge the extracellular domain of NRP1 to that of the scavenger receptor expressed by endothelial cells I (SREC-I), and induce NRP1 and SREC-I coordinate internalization and trafficking to the lysosomes. Overexpression of SREC-I in SREC-I-negative cells specifically reduces cell-surface levels of NRP1, indicating that SREC-I mediates NRP1 internalization. These results demonstrate that engineered receptor internalization is an effective strategy for reducing levels and function of cell-surface receptors, and identify certain sulfated polysaccharides as "internalization inducers." C1 [Narazaki, Masashi; Segarra, Marta; Tosato, Giovanna] NCI, NIH, Ctr Canc Res, Cellular Oncol Lab, Bethesda, MD 20892 USA. [Narazaki, Masashi] Osaka Univ, Grad Sch Med, Dept Resp Med Allergy & Rheumat Dis, Osaka, Japan. RP Tosato, G (reprint author), NCI, NIH, Ctr Canc Res, Cellular Oncol Lab, Bldg 37,Rm 4124, Bethesda, MD 20892 USA. EM tosatog@mail.nih.gov OI narazaki, masashi/0000-0002-5613-4409 FU Intramural NIH HHS NR 58 TC 27 Z9 28 U1 1 U2 5 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 APR 15 PY 2008 VL 111 IS 8 BP 4126 EP 4136 DI 10.1182/blood-2007-09-112474 PG 11 WC Hematology SC Hematology GA 290PM UT WOS:000255134700036 PM 18272814 ER PT J AU Oskeritzian, CA Alvarez, SE Hait, NC Price, MM Milstien, S Spiegel, S AF Oskeritzian, Carole A. Alvarez, Sergio E. Hait, Nitai C. Price, Megan M. Milstien, Sheldon Spiegel, Sarah TI Distinct roles of sphingosine kinases 1 and 2 in human mast-cell functions SO BLOOD LA English DT Article ID FC-EPSILON-RI; AIRWAY SMOOTH-MUSCLE; SPHINGOSINE-1-PHOSPHATE RECEPTORS; IGE; ACTIVATION; ASTHMA; DEGRANULATION; ALPHA; TRANSACTIVATION; STIMULATION AB Sphingosine-1-phosphate (S1P) is now emerging as a potent lipid mediator produced by mast cells that contributes to inflammatory and allergic responses. In contrast to its weak effect on degranulation of murine mast cells, S1P potently induced degranulation of the human LAD2 mast-cell line and cord blood-derived human mast cells (WCs). S1P also stimulated production and secretion of cytokines, TNF-alpha and IL-6, and markedly enhanced secretion of a chemokine, CCL2/MCP-1, important modulators of inflammation. S1P is produced in mast cells by the 2 sphingosine kinases, SphK1 and SphK2. SphK1 but not SphK2 plays a critical role in IgE/Ag-induced degranulation, migration toward antigen, and CCL2 secretion from hMCs, as determined by specifically down-regulating their expression. However, both isoenzymes were required for efficient TNF-alpha secretion. Taken together, our data suggest that differential formation of S1P by SphK1 and SphK2 has distinct and important actions in hMCs. C1 [Oskeritzian, Carole A.; Alvarez, Sergio E.; Hait, Nitai C.; Price, Megan M.; Spiegel, Sarah] Virginia Commonwealth Univ, Med Coll Virginia, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Milstien, Sheldon] NIMH, NIH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Sch Med, Dept Biochem & Mol Biol, 1101 E Marshall St, Richmond, VA 23298 USA. EM sspiegel@vcu.edu FU Intramural NIH HHS; NCI NIH HHS [R01 CA061774]; NIAID NIH HHS [R01 AI050094, R01 AI050094-05, R01AI50094]; NIAMS NIH HHS [K01 AR053186, K01AR053186] NR 33 TC 73 Z9 74 U1 0 U2 5 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 APR 15 PY 2008 VL 111 IS 8 BP 4193 EP 4200 DI 10.1182/blood-2007-09-115451 PG 8 WC Hematology SC Hematology GA 290PM UT WOS:000255134700043 PM 18178871 ER PT J AU Mielke, S Nunes, R Rezvani, K Fellowes, VS Venne, A Solomon, SR Fan, Y Gostick, E Price, DA Scotto, C Read, EJ Barrett, AJ AF Mielke, Stephan Nunes, Raquel Rezvani, Katayoun Fellowes, Vicki S. Venne, Annie Solomon, Scott R. Fan, Yong Gostick, Emma Price, David A. Scotto, Christian Read, Elizabeth J. Barrett, A. John TI A clinical-scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique SO BLOOD LA English DT Article ID GRAFT-VERSUS-HOST; BONE-MARROW-TRANSPLANTATION; ANTI-CD25 IMMUNOTOXIN; IMMUNE RECONSTITUTION; LEUKEMIA-CELLS; DEPLETION; DISEASE; GVHD; RISK; ALLOREACTIVITY AB Selective allodepletion is a strategy to eliminate host-reactive donor T cells from hematopoietic stem cell allografts to prevent graft-versus-host disease while conserving useful donor immune functions. To overcome fluctuations in activation-based surface marker expression and achieve a more consistent and effective allodepletion, we investigated a photodepletion process targeting activation-based changes in p-glycoprotein that result in an altered efflux of the photosensitizer TH9402. Expanded lymphocytes, generated using anti-CD3 and IL-2, were cocultured with responder cells from HLA-matched or -mismatched donors. Optimal results were achieved when cocultured cells were incubated with 7.5 mu M TH9402, followed by dye extrusion and exposure to 5 Joule/cm(2) light energy at 5 x 10(6), cells/mL. In mismatched stimulator-responder pairs, the median reduction of alloreactivity was 474-fold (range, 43-fold to 864-fold) compared with the unmanipulated responder. Third-party responses were maintained with a median 1.4-fold (range, 0.9-fold to 3.3-fold) reduction. In matched pairs, alloreactive helper T-lymphocyte precursors were reduced to lower than 1:100 000, while third-party responses remained higher than 1:10 000. This establishes a clinical-scale process capable of highly efficient, reproducible, selective removal of alloreactive lymphocytes from lymphocyte transplant products performed undercurrent Good Manufacturing Practice. This procedure is currently being investigated in a clinical trial of allotransplantation. C1 [Mielke, Stephan; Nunes, Raquel; Rezvani, Katayoun; Solomon, Scott R.; Barrett, A. John] NHLBI, Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Fellowes, Vicki S.; Fan, Yong; Read, Elizabeth J.] NIH, Cell Proc Sect, Dept Transfus Med, Bethesda, MD 20892 USA. [Venne, Annie] Kiadis Pharma Celmed, St Laurent, PQ, Canada. [Gostick, Emma; Price, David A.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. RP Mielke, S (reprint author), NHLBI, Stem Cell Allogene Transplant Sect, Hematol Branch, NIH, Bldg 10 CRC Rm 3-5288,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. EM mielkes@nhlbi.nih.gov RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Medical Research Council [, G0501963, MC_G0802523] NR 36 TC 70 Z9 71 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 APR 15 PY 2008 VL 111 IS 8 BP 4392 EP 4402 DI 10.1182/blood-2007-08-104471 PG 11 WC Hematology SC Hematology GA 290PM UT WOS:000255134700064 PM 17878399 ER PT J AU Azad, NS Annunziata, CM Steinberg, SM Minasian, L Premkumar, A Chow, C Kotz, HL Kohn, EC AF Azad, Nilofer S. Annunziata, Christina M. Steinberg, Seth M. Minasian, Lori Premkumar, Ahalya Chow, Catherine Kotz, Herbert L. Kohn, Elise C. TI Lack of reliability of CA125 response criteria with anti-VEGF molecularly targeted therapy SO CANCER LA English DT Article DE CA125; sorafenib; bevacizumab; VEGF; ovarian cancer ID EPITHELIAL OVARIAN-CANCER; PEGYLATED LIPOSOMAL DOXORUBICIN; PRIMARY PERITONEAL CANCER; RISING SERUM CA-125; CA 125; INDUCTION CHEMOTHERAPY; RECURRENT OVARIAN; TUMOR-MARKERS; SOLID TUMORS; NORMAL RANGE AB BACKGROUND. CA125 is an accepted indicator of epithelial ovarian cancer (EOC) response and is used to monitor patients treated with cytotoxic chemotherapy. It is uncertain how CA125 is affected by molecularly targeted drugs. In this pilot study, the authors analyzed the utility of CA125 to predict disease behavior in patients who were receiving sorafenib, a Raf-kinase/VEGFR2 inhibitor, and bevacizumab, an anti-VEGF monoclonal antibody. METHODS. Fifteen of 42 patients had recurrent EOC. Patients received sorafenib 200 mg orally twice daily or D1-5 of 7 and bevacizumab 5 mg/kg to 10 mg/kg intravenously every 2 weeks for 28-day cycles. Computed tomography (CT) scans were performed every 2 cycles for restaging, and CA125 was measured monthly. CA125 concentrations were retrospectively analyzed as a function of clinical behavior. RESULTS. Fourteen of 15 patients had abnormal CA125 concentrations at study entry (median 1056 U/mL; range, 67 U/mL to 9813 U/mL). Seven (47%) patients had partial response by imaging criteria. Five of these 7 patients had partial response by CA125 criteria (71% sensitivity). Eight (53%) patients would have had partial responses if CA125 criteria were used; only 5 were confirmed by CT (63 % specificity). Imaging and CA125 criteria combined yielded a higher total response rate of 10 of 15 (67%). Three patients with objective partial response by imaging lasting >20, >22, and >24 cycles would have terminated treatment prematurely if CA125 had been used. CONCLUSIONS. CA125 changes may not correspond to imaging response criteria for ECC patients who are receiving sorafenib and bevacizumab. Caution is recommended when using CA125 as a response criterion of molecularly targeted agents until prospective studies validate CA125 changes with objective imaging response results. C1 [Azad, Nilofer S.; Annunziata, Christina M.; Minasian, Lori; Kotz, Herbert L.; Kohn, Elise C.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kohn, Elise C.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Premkumar, Ahalya; Chow, Catherine] NIH, Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Azad, NS (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr 12N226, Bethesda, MD 20892 USA. EM azadn@mail.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 FU Intramural NIH HHS NR 39 TC 22 Z9 22 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2008 VL 112 IS 8 BP 1726 EP 1732 DI 10.1002/cncr.23374 PG 7 WC Oncology SC Oncology GA 288XH UT WOS:000255018900011 PM 18300236 ER PT J AU Bacolod, MD Schemmann, GS Wang, S Shattock, R Giardina, SF Zeng, ZS Shia, JR Stengel, RF Gerry, N Hoh, J Kirchhoff, T Gold, B Christman, MF Offit, K Gerald, WL Notterman, DA Ott, J Paty, PB Barany, F AF Bacolod, Manny D. Schemmann, Gunter S. Wang, Shuang Shattock, Richard Giardina, Sarah F. Zeng, Zhaoshi Shia, Jinru Stengel, Robert F. Gerry, Norman Hoh, Josephine Kirchhoff, Tomas Gold, Bert Christman, Michael F. Offit, Kenneth Gerald, William L. Notterman, Daniel A. Ott, Jurg Paty, Philip B. Barany, Francis TI The signatures of autozygosity among patients with colorectal cancer SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; UNIPARENTAL DISOMY; GENE-EXPRESSION; HAPLOTYPE MAP; COLON-CANCER; RISK; MUTATIONS; DISEASE; SUSCEPTIBILITY; FAMILIES AB Previous studies have shown that among populations with a high rate of consanguinity, there is a significant increase in the prevalence of cancer. Single nucleotide polymorphism (SNP) array data (Affymetrix, 50K XbaI) analysis revealed long regions of homozygosity in genomic DNAs taken from tumor and matched normal tissues of colorectal cancer (CRC) patients. The presence of these regions in the genome may indicate levels of consanguinity in the individual's family lineage. We refer to these autozygous regions as identity-by-descent (IBD) segments. In this study, we compared IBD segments in 74 mostly Caucasian CRC patients (mean age of 66 years) to two control data sets: (a) 146 Caucasian individuals (mean age of 80 years) who participated in an age-related macular degeneration (AMD) study and (b) 118 cancer-free Caucasian individuals from the Framingham Heart Study (mean age of 67 years). Our results show that the percentage of CRC patients with IBD segments (>= 4 Mb length and 50 SNPs probed) in the genome is at least twice as high as the AMD or Framingham control groups. Also, the average length of these IBD regions in the CRC patients is more than twice the length of the two control data sets. Compared with control groups, IBD segments are found to be more common among individuals of Jewish background. We believe that these HID segments within CRC patients are likely to harbor important CRC-related genes with low-penetrance SNPs and/or mutations, and, indeed, two recently identified CRC predisposition SNPs in the 8q24 region were confirmed to be homozygous in one particular patient carrying an IBD segment covering the region. C1 [Bacolod, Manny D.; Shattock, Richard; Giardina, Sarah F.; Barany, Francis] Cornell Univ, Weill Med Coll, Dept Microbiol, New York, NY 10021 USA. [Wang, Shuang] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10027 USA. [Zeng, Zhaoshi; Paty, Philip B.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY USA. [Shia, Jinru; Gerald, William L.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Kirchhoff, Tomas; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Ott, Jurg] Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. [Schemmann, Gunter S.; Stengel, Robert F.] Princeton Univ, Sch Engn & Appl Sci, Princeton, NJ 08544 USA. [Notterman, Daniel A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. [Gold, Bert] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Gerry, Norman; Christman, Michael F.] Boston Univ, Dept Genet & Genom, Boston, MA 02215 USA. [Hoh, Josephine] Yale Univ, Sch Publ Hlth, New Haven, CT USA. RP Barany, F (reprint author), Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. EM barany@med.cornell.edu OI Shia, Jinru/0000-0002-4351-2511; Kirchhoff, Tomas/0000-0002-9055-2364 FU NCI NIH HHS [P01 CA065930, P01-CA65930]; NICHD NIH HHS [P2C HD047879] NR 50 TC 33 Z9 33 U1 0 U2 1 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 APR 15 PY 2008 VL 68 IS 8 BP 2610 EP 2621 DI 10.1158/0008-5472.CAN-07-5250 PG 12 WC Oncology SC Oncology GA 290CM UT WOS:000255100500011 PM 18375840 ER PT J AU Nadella, KS Jones, GN Trimboli, A Stratakis, CA Leone, G Kirschner, LS AF Nadella, Kiran S. Jones, Georgette N. Trimboli, Anthony Stratakis, Constantine A. Leone, Gustavo Kirschner, Lawrence S. TI Targeted deletion of Prkar1a reveals a role for protein kinase A in mesenchymal-to-epithelial transition SO CANCER RESEARCH LA English DT Article ID ALPHA REGULATORY SUBUNIT; CARNEY COMPLEX; ADRENOCORTICAL TUMORS; CARDIAC MYXOMAS; NEURAL CREST; CYCLIC-AMP; I-ALPHA; GENE; MUTATIONS; EXPRESSION AB Dysregulation of protein kinase A (PKA) activity, caused by loss of function mutations in PRKAR1A, is known to induce tumor formation in the inherited tumor syndrome Carney complex (CNC) and is also associated with sporadic tumors of the thyroid and adrenal. We have previously shown that Prkar1a(+/-) mice develop schwannomas reminiscent of those seen in CNC and that similar tumors are observed in tissue-specific knockouts (KO) of Prkar1a targeted to the neural crest. Within these tumors, we have previously described the presence of epithelial islands, although the nature of these structures was unclear. In this article, we report that these epithelial structures are derived from KO cells originating in the neural crest. Analysis of the mesenchymal marker vimentin revealed that this protein was markedly down-regulated not only from the epithelial islands, but also from the tumor as a whole, consistent with mesenchymal-to-epithelial transition (MET). In vitro, Prkar1a null primary mouse embryonic fibroblasts, which display constitutive PKA signaling, also showed evidence for MET, with a loss of vimentin and up-regulation of the epithelial marker E-cadherin. Reduction of vimentin protein occurred at the posttranslational level and was rescued by proteasomal inhibition. Finally, this down-regulation of vimentin was recapitulated in the adrenal nodules of CNC patients, confirming an unexpected and previously unrecognized role for PKA in MET. C1 [Nadella, Kiran S.; Jones, Georgette N.; Trimboli, Anthony; Leone, Gustavo; Kirschner, Lawrence S.] Ohio State Univ, Human Canc Genet Program, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Kirschner, Lawrence S.] Ohio State Univ, Div Endocrinol Diabet & Metab, Dept Internal Med, Columbus, OH 43210 USA. [Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Kirschner, LS (reprint author), 420 W 12th Ave TMRF 544, Columbus, OH 43210 USA. EM Kirschner@osume.edu RI Jones, Georgette/B-3181-2012; Kirschner, Lawrence/E-3392-2011 FU Intramural NIH HHS [ZIA HD000642-13]; NCI NIH HHS [R01 CA112268, CA112268-02, CA16058, P30 CA016058]; NICHD NIH HHS [Z01 HD000642, HD01323, K22 HD001323] NR 43 TC 23 Z9 24 U1 0 U2 1 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 APR 15 PY 2008 VL 68 IS 8 BP 2671 EP 2677 DI 10.1158/0008-5472.CAN-07-6002 PG 7 WC Oncology SC Oncology GA 290CM UT WOS:000255100500017 PM 18413734 ER PT J AU Sun, LC Huang, L Nguyen, P Bisht, KS Bar-Sela, G Ho, AS Bradbury, CM Yu, WQ Cui, HM Lee, SM Trepel, JB Feinberg, AP Gius, D AF Sun, Lunching Huang, Lei Nguyen, Phuongmai Bisht, Kheem S. Bar-Sela, Gil Ho, Allen S. Bradbury, C. Matthew Yu, Wenqiang Cui, Hengmi Lee, Sunmin Trepel, Jane B. Feinberg, Andrew P. Gius, David TI DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation SO CANCER RESEARCH LA English DT Article ID ENHANCER-BLOCKING ACTIVITY; CANCER-CELLS; HEAT-SHOCK; CTCF; TRANSCRIPTION; FAMILY; DOMAIN; GENES; IGF2; INSULATOR AB In a previous genomic analysis, using somatic methyltransferase (DNMT) knockout cells, we showed that hypomethylation decreased the expression of as many genes as were observed to increase, suggesting a previously unknown mechanism for epigenetic regulation. To address this idea, the expression of the BAG family genes was used as a model. These genes were used because their expression was decreased in DNMT1(-/-) DNMT3B(-/-), and double knockout cells and increased in DNMT1-overexpressing and DNMT3B-overexpressing cells. Chromatin immunoprecipitation analysis of the BAG-1 promoter in DNMT1-overexpressing or DNMT3B-overexpressing cells showed a permissive dimethyl-H3-K4/dimethyl-H3-K9 chromatin status associated with DNA-binding of CTCFL/BORIS, as well as increased BAG-1 expression. In contrast, a nonpermissive dimethyl-H3-M/dimethyl-M-K9 chromatin status was associated with CTCF DNA-binding and decreased BAG-1 expression in the single and double DNMT knockout cells. BORIS short hairpin RNA knockdown decreased both promoter DNA-binding, as well as BAG-1 expression, and changed the dimethyl-H3-K4/dimethyl-H3-K9 ratio to that characteristic of a nonpermissive chromatin state. These results suggest that DNMT1 and DNMT3B regulate BAG-1 expression via insulator protein DNA-binding and chromatin dynamics by regulating histone dimethylation. C1 [Yu, Wenqiang; Cui, Hengmi; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Yu, Wenqiang; Cui, Hengmi; Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. [Sun, Lunching; Huang, Lei; Nguyen, Phuongmai; Bisht, Kheem S.; Bar-Sela, Gil; Ho, Allen S.; Bradbury, C. Matthew; Gius, David] NCI, Radiat Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Lee, Sunmin; Trepel, Jane B.] NCI, Med Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Feinberg, AP (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, 720 Rutland Ave, Baltimore, MD 21205 USA. EM afeinberg@jhu.edu; giusd@mail.nih.gov FU Intramural NIH HHS [Z01 BC010544-04]; NCI NIH HHS [CA72602, CA75556, R01 CA065145, R37 CA054358, R37 CA054358-18, CA65145] NR 38 TC 25 Z9 30 U1 0 U2 5 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 APR 15 PY 2008 VL 68 IS 8 BP 2726 EP 2735 DI 10.1158/0008-5472.CAN-07-6654 PG 10 WC Oncology SC Oncology GA 290CM UT WOS:000255100500023 PM 18413740 ER PT J AU Janicki, CN Jenkinson, SR Williams, NA Morgan, DJ AF Janicki, Claire N. Jenkinson, S. Rhiannon Williams, Neil A. Morgan, David J. TI Loss of CTL function among high-avidity tumor-specific CD8(+) T cells following tumor infiltration SO CANCER RESEARCH LA English DT Article ID CANCER-IMMUNOTHERAPY; CROSS-PRESENTATION; INTERFERON-GAMMA; TOLERANCE; ANTIGENS; LYMPHOCYTES; ACTIVATION; RESPONSES; IDENTIFICATION; GENERATION AB A major problem in generating effective antitumor CTL responses is that most tumors express self-antigens to which the immune system is rendered unresponsive due to mechanisms of self-tolerance induction. CTL precursors (CTLp) expressing high-affinity T-cell receptors (TCR) are often functionally deleted from the repertoire, leaving a residual repertoire of CTLp having only low-affinity TCR. Furthermore, even when unique antigens are expressed, their presentation by dendritic cells (DC) may predispose to peripheral tolerance induction rather than the establishment of CTL responses that kill tumor cells. In this study, we examined both high-avidity (CL4) and low-avidity (CL1) CD8(+) T-cell responses to a murine renal carcinoma expressing, as a neoantigen, high and low levels of the hemagglutinin (RA) protein from influenza virus A/PR/8 H1N1 (PR8; RencaHA(high) and RencaHA(low)). Our data show that, following encounter with K(d)HA epitopes cross-presented by bone marrow-derived DC, low-avidity CL1 cells become tolerized within tumor-draining lymph nodes (TDLN), and in mice bearing either RencaHA(high) or RencaHA(low) tumors, very few form tumor-infiltrating lymphocytes (TIL). In marked contrast, high-avidity CL4 cells differentiate into effector CTL within the TDLN of mice bearing either RencaA(high) or RencaHA(low) tumors, and although they form TIL in both tumors, they lose CTL effector function. Critically, these results show that anticancer therapies involving either adoptive transfer of high-avidity tumor-specific CTL populations or targeting of preexisting tumor antigen-specific memory CD8(+) T cells could fail due to the fact that CTL effector function is lost following tumor infiltration. C1 [Janicki, Claire N.; Williams, Neil A.; Morgan, David J.] Univ Bristol, Sch Med Sci, Dept Cellular & Mol Med, Bristol BS8 1TD, Avon, England. [Jenkinson, S. Rhiannon] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Morgan, DJ (reprint author), Univ Bristol, Sch Med Sci, Dept Cellular & Mol Med, Univ Walk, Bristol BS8 1TD, Avon, England. EM d.j.morgan@bristol.ac.uk FU Cancer Research UK [C1484/A5199] NR 31 TC 36 Z9 36 U1 0 U2 8 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 APR 15 PY 2008 VL 68 IS 8 BP 2993 EP 3000 DI 10.1158/0008-5472.CAN-07-5008 PG 8 WC Oncology SC Oncology GA 290CM UT WOS:000255100500053 PM 18413769 ER PT J AU Purdue, MP Graubard, BI Chanock, SJ Rubertone, MV Erickson, RL McGlynn, KA AF Purdue, Mark P. Graubard, Barry I. Chanock, Stephen J. Rubertone, Mark V. Erickson, Ralph L. McGlynn, Katherine A. TI Genetic variation in the inhibin pathway and risk of testicular germ cell tumors SO CANCER RESEARCH LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; PREMATURE OVARIAN FAILURE; MUTATIONAL ANALYSIS; PROSTATE-CANCER; ALPHA-SUBUNIT; HUMAN GENOME; ASSOCIATION; POLYMORPHISMS; FOLLISTATIN; SUPPRESSOR AB Gene-knockout studies in mice suggest that INHA, encoding a subunit of gonadotropin-regulating proteins known as inhibins, is a tumor suppressor for testicular stromal cell tumors. It is not known whether genetic variation in the inhibin pathway also influences susceptibility to testicular germ cell tumors (TGCT), the most common testicular cancer in young men. To address this question, we conducted a case-control analysis (577 cases; 707 controls) of single-nucleotide polymorphisms (SNP) in genes in the inhibin pathway among participants in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study. Thirty-eight tagging SNPs in six genes (INHA, INHBA, INHBB, INHBC, INHBE, and SMAD4) were genotyped. Odds ratios (OR) and 95% confidence intervals (0) relating variant genotypes to TGCT risk were calculated using unconditional logistic regression. Among White subjects, an elevated risk of TGCT was observed for carriers of the T allele of the INHA variant rs2059693 (CT genotype: OR, 1.33; 95% CI, 1.04-1.71; TT: OR, 1.60; 95% CI, 1.01-2.52; P-trend = 0.008). The association with rs2059693 was stronger for nonseminomas, and for teratomas and teratocarcinomas in particular (N = 58; CT: OR, 1.63; 95% CI, 0.89-2.99; TT: OR, 4.54; 95% CI 2.00-10.3; P-trend = 0.0008). We found no evidence of association with variants in the other investigated genes. These findings suggest that genetic variation in the INHA locus influences TGCT development. C1 [Purdue, Mark P.; Graubard, Barry I.; McGlynn, Katherine A.] NCI, Div Canc Epiodemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chanock, Stephen J.] Natl Canc Inst Core Genotyping Facil, NIH, Dept Hlth & Human Dev, Gaithersburg, MD USA. [Rubertone, Mark V.] USA, Ctr Hlth Promot & Prevent Med, Washington, DC USA. [Erickson, Ralph L.] Walter Reed Army Inst Res, Forest Glen, MD USA. RP Purdue, MP (reprint author), NCI, Div Canc Epiodemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,Dept Hlth & Human Serv, EPS 8009,6120 Execut Blvd, Bethesda, MD 20892 USA. EM purduem@mail.nih.gov RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU Intramural NIH HHS [Z01 CP010158-07] NR 36 TC 9 Z9 9 U1 0 U2 2 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 APR 15 PY 2008 VL 68 IS 8 BP 3043 EP 3048 DI 10.1158/0008-5472.CAN-07-5852 PG 6 WC Oncology SC Oncology GA 290CM UT WOS:000255100500059 PM 18413775 ER PT J AU Yang, HH Hu, Y Lee, MP Hu, N Ng, D Goldstein, AM Wang, CY Taylor, PR AF Yang, Howard H. Hu, Ying Lee, Maxwell P. Hu, Nan Ng, David Goldstein, Alisa M. Wang, Chaoyu Taylor, Philip R. TI A statistical reappraisal of the findings of an Esophageal cancer genome-wide association study - Response SO CANCER RESEARCH LA English DT Letter ID CHINA C1 [Yang, Howard H.; Hu, Ying; Lee, Maxwell P.] Ctr Canc Res, Lab Populat Genet, Bethesda, MD 20892 USA. [Hu, Nan; Ng, David; Goldstein, Alisa M.; Wang, Chaoyu; Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Yang, HH (reprint author), Ctr Canc Res, Lab Populat Genet, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 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 APR 15 PY 2008 VL 68 IS 8 BP 3075 EP 3075 DI 10.1158/0008-5472.CAN-07-6426 PG 1 WC Oncology SC Oncology GA 290CM UT WOS:000255100500064 ER PT J AU Sharma, S Brosh, RM AF Sharma, Sudha Brosh, Robert M., Jr. TI Unique and important consequences of RECQ1 deficiency in mammalian cells SO CELL CYCLE LA English DT Review DE RECQ1 (RECQL); helicase; genomic instability; cancer; DNA repair; recQ; replication; homologous recombination; gene silencing ID REPLICATION PROTEIN-A; BLOOMS-SYNDROME HELICASE; WERNER-SYNDROME PROTEIN; SINGLE-STRANDED-DNA; SISTER-CHROMATID EXCHANGE; ROTHMUND-THOMSON-SYNDROME; MISMATCH REPAIR PROTEINS; TOPOISOMERASE III-ALPHA; SYNDROME GENE-PRODUCT; SACCHAROMYCES-CEREVISIAE AB Five members of the RecQ subfamily of DEx-H-containing DNA helicases have been identified in both human and mouse, and mutations in BLM, WRN and RECQ4 are associated with human diseases of premature aging, cancer, and chromosomal instability. Although a genetic disease has not been linked to RECQ1 mutations, RECQ1 helicase is the most highly expressed of the human RecQ helicases, suggesting an important role in cellular DNA metabolism. Recent advances have elucidated a unique role of RECQ1 to suppress genomic instability. Embryonic fibroblasts from RECQ1-deficient mice displayed aneuploidy, chromosomal instability, and increased load of DNA damage. 1 Acute depletion of human RECQ1 renders cells sensitive to DNA damage and results in spontaneous gamma-H2AX foci and elevated sister chromatid exchanges, indicating aberrant repair of DNA breaks. 2 Consistent with a role in DNA repair, RECQ1 relocalizes to irradiation-induced nuclear foci and associates with chromatin. 2 RECQ1 catalytic activities3 and interactions with DNA repair proteins(2,4,5) are likely to be important for its molecular functions in genome homeostasis. Collectively, these studies provide the first evidence for an important role of RECQ1 to confer chromosomal stability that is unique from that of other RecQ helicases and suggest its potential involvement in tumorigenesis. C1 [Sharma, Sudha; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, Dept Hlth & Human Serv, 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 [Z01 AG000741-07] NR 137 TC 24 Z9 24 U1 1 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 APR 15 PY 2008 VL 7 IS 8 BP 989 EP 1000 DI 10.4161/cc.7.8.5707 PG 12 WC Cell Biology SC Cell Biology GA 304IG UT WOS:000256102600005 PM 18414032 ER PT J AU Gong, F Fahy, D Liu, H Wang, WD Smerdon, MJ AF Gong, Feng Fahy, Deirdre Liu, Hong Wang, Weidong Smerdon, Michael J. TI Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damage SO CELL CYCLE LA English DT Article DE Swi/Snf; chromatin remodeling; UV damage response; DNA repair; Gadd45a; p21; BAF complex; checkpoint ID NUCLEOTIDE EXCISION-REPAIR; INDUCED 6-4 PHOTOPRODUCTS; STRAND BREAK REPAIR; DNA-DAMAGE; TRANSCRIPTIONAL ACTIVATORS; RETINOBLASTOMA PROTEIN; MULTISUBUNIT COMPLEX; CYCLE CHECKPOINTS; TUMOR SUPPRESSION; NUCLEAR ANTIGEN AB Mammalian cells exhibit complex cellular responses to DNA damage, including cell cycle arrest, DNA repair and apoptosis. Defects in any one of these responses can result in carcinogenesis. Absence of the chromatin remodeling complex Swi/Snf is found in many instances of cancer, and we have investigated its role in the UV damage response. The human carcinoma cell line SW13 is deficient in Swi/Snf and is very sensitive to UV radiation. In contrast, SW13 cells with ectopic Brg1 expression regain active Swi/Snf and become significantly more resistant to UV radiation. Sensitivity to UV light correlates well with dramatic UV induced apoptosis in SW13 cells, but not in SW13 cells expressing Brg1. We show that SW13 cells synchronized at the G1/S border progress into S phase after UV irradiation, and this checkpoint deficiency is corrected after Brg1 expression is restored. Interestingly, Brg1 expression in SW13 cells restores expression of two DNA damage responsive genes, Gadd45a and p21. Furthermore, Gadd45a induction and p21 degradation were observed in the Brg1-expressing SW13 cells after UV irradiation. Our findings demonstrate that Swi/ Snf protects cells against deleterious consequences of UV induced DNA damage. These results also indicate that Swi/Snf may modulate checkpoint activation after UV damage via regulation of the two PCNA-binding proteins Gadd45a and p21. C1 [Gong, Feng; Fahy, Deirdre; Smerdon, Michael J.] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. [Liu, Hong] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. [Wang, Weidong] NIA, Genet Lab, Baltimore, MD 21224 USA. RP Smerdon, MJ (reprint author), Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. EM fgong@med.miami.edu; smerdon@wsu.edu FU Intramural NIH HHS; NIEHS NIH HHS [ES02614, ES04106] NR 61 TC 50 Z9 51 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 APR 15 PY 2008 VL 7 IS 8 BP 1067 EP 1074 DI 10.4161/cc.7.8.5647 PG 8 WC Cell Biology SC Cell Biology GA 304IG UT WOS:000256102600013 PM 18414052 ER PT J AU Weichsel, R Dix, C Wooldridge, L Clement, M Fenton-May, A Sewell, AK Zezula, J Greiner, E Gostick, E Price, DA Einsele, H Seggewiss, R AF Weichsel, Ralf Dix, Carolin Wooldridge, Linda Clement, Matthew Fenton-May, Angharad Sewell, Andrew K. Zezula, Josef Greiner, Elisabeth Gostick, Emma Price, David A. Einsele, Hermann Seggewiss, Ruth TI Profound inhibition of antigen-specific T-cell effector functions by dasatinib SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; IMATINIB MESYLATE; IN-VITRO; CYTOGENETIC RESPONSES; KINASE INHIBITOR; ACTIVATION; GAMMA; TRANSPLANTATION; RESISTANT AB Purpose: The dual BCR-ABL/SRC kinase inhibitor dasatinib entered the clinic for the treatment of chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia. Because SRC kinases are known to play an important role in physiologic T-cell activation, we analyzed the immunobiological effects of clasatinib on T-cell function. The effect of clasatinib on multiple T-cell effector functions was examined at clinically relevant doses (1-100 nmol/L); the promiscuous tyrosine kinase inhibitor staurosporine was used as a comparator. Experimental Design: Purified human CD3(+) cells and virus-specific CD8(+) T cells from healthy blood donors were studied directly ex vivo; antigen-specific effects were confirmed in defined T-cell clones. Functional outcomes included cytokine production (interleukin-2, IFN-gamma, and tumor necrosis factor alpha), clegranulation (CD107a/b mobilization), activation (CD69 up-regulation), proliferation (carboxyfluorescein diacetate succinimidyl ester dilution), apoptosis/necrosis induction, and signal transduction. Results: Both clasatinib and staurosporine inhibited T-cell activation, proliferation, cytokine production, and clegranulation in a dose-dependent manner. Mechanistically, this was mediated by the blockade of early signal transduction events and was not due to loss of T-cell viability. Overall, CD4(+) T cells seemed to be more sensitive to these effects than CD8+ T cells, and naive T cells more sensitive than memory T-cell subsets. The inhibitory effects of clasatinib were so profound that all T-cell effector functions were shut down at therapeutically relevant concentrations. Conclusion: These findings indicate that caution is warranted with use of this drug in the clinical setting and provide a rationale to explore the potential of clasatinib as an immunosuppressant in the fields of transplantation and T-cell - driven autoimmune diseases. C1 [Weichsel, Ralf; Dix, Carolin; Einsele, Hermann; Seggewiss, Ruth] Univ Wurzburg, Med Klin & Poliklin 2, Immune Recovery Sect, D-97080 Wurzburg, Germany. [Wooldridge, Linda; Clement, Matthew; Fenton-May, Angharad; Sewell, Andrew K.] Cardiff Univ, Dept Med Biochem & Immunol, Cardiff, Wales. [Zezula, Josef; Greiner, Elisabeth] NIDDKD, NIH, Med Chem Lab, Bethesda, MD 20892 USA. [Gostick, Emma; Price, David A.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. RP Seggewiss, R (reprint author), Univ Wurzburg, Med Klin & Poliklin 2, Immune Recovery Sect, C11,Room E02,Josef Schneider Str 2, D-97080 Wurzburg, Germany. EM Seggewiss_R@medizin.uni-wuerzburg.de RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Sewell, Andrew/0000-0003-3194-3135; Fenton-May, Angharad/0000-0002-6267-1315 FU Medical Research Council [G0501963] NR 37 TC 68 Z9 68 U1 0 U2 1 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 APR 15 PY 2008 VL 14 IS 8 BP 2484 EP 2491 DI 10.1158/1078-0432.CCR-07-4393 PG 8 WC Oncology SC Oncology GA 287VC UT WOS:000254943600031 PM 18413841 ER PT J AU Powers, JH AF Powers, John H. TI Reassessing the design, conduct, and analysis of clinical trials of therapy for community-acquired pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID BACTEREMIA; OUTCOMES C1 [Powers, John H.] NIAID, Collaborat Clin Res Branch, NIH, Bethesda, MD 20892 USA. [Powers, John H.] George Washington Univ, Sch Med, Bethesda, MD USA. [Powers, John H.] Univ Maryland, Sch Med, Bethesda, MD USA. RP Powers, JH (reprint author), 6700B Rockledge Dr,Rm 1123, Bethesda, MD 20892 USA. EM powers.john@mail.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 24 TC 5 Z9 5 U1 0 U2 0 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 APR 15 PY 2008 VL 46 IS 8 BP 1152 EP 1156 DI 10.1086/533442 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 285CH UT WOS:000254754400006 PM 18444849 ER PT J AU Andrade, A Bailey, JR Xu, J Philp, FH Quinn, TC Williams, TM Ray, SC Thomas, DL Blankson, JN AF Andrade, Adriana Bailey, Justin R. Xu, Jie Philp, Frances H. Quinn, Thomas C. Williams, Thomas M. Ray, Stuart C. Thomas, David L. Blankson, Joel N. TI CD4(+) T cell depletion in an untreated HIV type1-infected human leukocyte antigen-B*5801-positive patient with an undetectable viral load SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNE ACTIVATION; LYMPHOCYTE ACTIVATION; ELITE SUPPRESSORS; INFECTION; REPLICATION; BLOOD; HLA AB We report a case of a patient infected with human immunodeficiency virus type 1 (HIV-1) for 20 years who has experienced CD4(+) T cell depletion in spite of maintaining undetectable viral loads. Our data suggest that immune activation can cause CD4(+) T cell depletion even when HIV-1 replication appears to be controlled by host factors. C1 [Andrade, Adriana; Bailey, Justin R.; Xu, Jie; Philp, Frances H.; Quinn, Thomas C.; Ray, Stuart C.; Thomas, David L.; Blankson, Joel N.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA. [Williams, Thomas M.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Williams, Thomas M.] Tricore Reference Labs, Albuquerque, NM USA. RP Blankson, JN (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Broadway Res Bldg,Rm 880,733 N Broadway, Baltimore, MD 21205 USA. EM jblanks@jhmi.edu RI Ray, Stuart/B-7527-2008 OI Ray, Stuart/0000-0002-1051-7260 FU Intramural NIH HHS [Z01 AI000361-25]; NIAID NIH HHS [K08 AI051191, K08 AI51191, R56 AI073185, R56 AI73185-01A1]; NIDA NIH HHS [R01 DA016078] NR 15 TC 22 Z9 22 U1 0 U2 0 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 APR 15 PY 2008 VL 46 IS 8 BP E78 EP E82 DI 10.1086/529387 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 285CH UT WOS:000254754400038 PM 18444844 ER PT J AU Narbonne-Reveau, K Senger, S Pal, M Herr, A Richardson, HE Asano, M Deak, P Lilly, MA AF Narbonne-Reveau, Karine Senger, Stefania Pal, Margit Herr, Anabel Richardson, Helena E. Asano, Maki Deak, Peter Lilly, Mary A. TI APC/C(Fzr/Cdh1) promotes cell cycle progression during the Drosophila endocycle SO DEVELOPMENT LA English DT Article DE APC/C; cdh1; cyclin E; Drosophila; endoreplication; endocycle; Fzr/Cdh1; geminin ID DNA-REPLICATION; FOLLICLE CELLS; S-PHASE; MITOTIC CYCLINS; ENDOREDUPLICATION CYCLES; SUBSTRATE RECOGNITION; CHROMOSOME STRUCTURE; EUKARYOTIC CELLS; EYE DEVELOPMENT; CDC25 PROTEIN AB The endocycle is a commonly observed variant cell cycle in which cells undergo repeated rounds of DNA replication with no intervening mitosis. How the cell cycle machinery is modified to transform a mitotic cycle into endocycle has long been a matter of interest. In both plants and animals, the transition from the mitotic cycle to the endocycle requires Fzr/Cdh1, a positive regulator of the Anaphase-Promoting Complex/Cyclosome (APC/C). However, because many of its targets are transcriptionally downregulated upon entry into the endocycle, it remains unclear whether the APC/C functions beyond the mitotic/endocycle boundary. Here, we report that APC/C(Fzr/Cdh1) activity is required to promote the G/S oscillation of the Drosophila endocycle. We demonstrate that compromising APC/C activity, after cells have entered the endocycle, inhibits DNA replication and results in the accumulation of multiple APC/C targets, including the mitotic cyclins and Geminin. Notably, our data suggest that the activity of APC/CFzr/Cdh1 during the endocycle is not continuous but is cyclic, as demonstrated by the APC/C-dependent oscillation of the pre-replication complex component Orc1. Taken together, our data suggest a model in which the cyclic activity of APC/C(Fzr/Cdh1) during the Drosophila endocycle is driven by the periodic inhibition of Fzr/Cdh1 by Cyclin E/Cdk2. We propose that, as is observed in mitotic cycles, during endocycles, APC/C(Fzr/Cdh1) functions to reduce the levels of the mitotic cyclins and Geminin in order to facilitate the relicensing of DNA replication origins and cell cycle progression. C1 [Narbonne-Reveau, Karine; Senger, Stefania; Lilly, Mary A.] NICHHD, NIH, Cell Biol & Metab Program, Bethesda, MD 20892 USA. [Pal, Margit; Deak, Peter] Biol Res Ctr, Inst Biochem, H-6726 Szeged, Hungary. [Herr, Anabel; Richardson, Helena E.] Peter MacCallum Canc Ctr, Cell Cycle & Dev Lab, Melbourne, Vic 3002, Australia. [Asano, Maki] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. RP Lilly, MA (reprint author), NICHHD, NIH, Cell Biol & Metab Program, Bethesda, MD 20892 USA. EM mlilly@helix.nih.gov RI Deak, Peter/F-7751-2012; Richardson, Helena/A-8080-2013; OI Richardson, Helena/0000-0003-3852-4953; Lilly, Mary/0000-0003-1564-619X FU Intramural NIH HHS NR 81 TC 57 Z9 57 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 APR 15 PY 2008 VL 135 IS 8 BP 1451 EP 1461 DI 10.1242/dev.016295 PG 11 WC Developmental Biology SC Developmental Biology GA 287LD UT WOS:000254917700007 PM 18321983 ER PT J AU O'Bryan, MK Takada, S Kennedy, CL Scott, G Harada, S Ray, MK Dai, QS Wilhelm, D de Kretser, DM Eddy, EM Koopman, P Mishina, Y AF O'Bryan, Moira K. Takada, Shuji Kennedy, Claire L. Scott, Greg Harada, Shun-ichi Ray, Manas K. Dai, Qunsheng Wilhelm, Dagmar de Kretser, David M. Eddy, E. Mitch Koopman, Peter Mishina, Yuji TI Sox8 is a critical regulator of adult Sertoli cell function and male fertility SO DEVELOPMENTAL BIOLOGY LA English DT Article DE testis; fertility; Sox; sperm; adhesion; spermatogenesis ID NEURAL CREST DEVELOPMENT; AUTOSOMAL SEX REVERSAL; SRY-RELATED GENE; CAMPOMELIC DYSPLASIA; HIRSCHSPRUNG-DISEASE; MOUSE MODEL; MUTATIONS; SPERM; MICE; SPERMATOGENESIS AB Sox8 encodes a high-mobility group transcription factor that is widely expressed during development. Sox8, -9 and -10 form group E of the Sox gene family which has been implicated in several human developmental disorders. In contrast to other SoxE genes, the role of Sox8 is unclear and Sox8 mouse mutants reportedly showed only idiopathic weight loss and reduced bone density. The careful analysis of our Sox8 null mice, however, revealed a progressive male infertility phenotype. Sox8 null males only sporadically produced litters of reduced size at young ages. We have shown that SOX8 protein is a product of adult Sertoli cells and its elimination results in an age-dependent deregulation of spermatogenesis, characterized by sloughing of spermatocytes and round spermatids, spermiation failure and a progressive disorganization of the spermatogenic cycle, which resulted in the inappropriate placement and juxtaposition of germ cell types within the epithelium. Those sperm that did enter the epididymides displayed abnormal motility. These data show that SOX8 is a critical regulator of adult Sertoli cell function and is required for both its cytoarchitectural and paracrine interactions with germ cells. Crown Copyright (C) 2008 Published by Elsevier Inc. All rights reserved. C1 [O'Bryan, Moira K.; Kennedy, Claire L.; de Kretser, David M.] Monash Univ, Monash Inst Med Res, Melbourne, Vic 3004, Australia. [Takada, Shuji; Wilhelm, Dagmar; Koopman, Peter] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. [Scott, Greg; Ray, Manas K.; Mishina, Yuji] Natl Inst Environm Hlth Sci, Knockout Core, Res Triangle Pk, NC 27709 USA. [Mishina, Yuji] Natl Inst Environm Hlth Sci, Mol Dev Biol Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Eddy, E. Mitch] Natl Inst Environm Hlth Sci, Gamete Biol Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Harada, Shun-ichi] Merck Res Labs, Dept Bone Biol & Osteoporosis Res, West Point, PA USA. RP O'Bryan, MK (reprint author), Monash Univ, Monash Inst Med Res, Melbourne, Vic 3004, Australia. EM moira.obryan@med.monash.edu.au; mishina@niehs.nih.gov RI Koopman, Peter /C-9416-2009; Wilhelm, Dagmar/B-6915-2009; O'Bryan, Moira/F-8256-2012 OI Koopman, Peter /0000-0001-6939-0914; Wilhelm, Dagmar/0000-0002-7757-4075; O'Bryan, Moira/0000-0001-7298-4940 FU Intramural NIH HHS [Z01 ES070076-21]; NIEHS NIH HHS [ES071003-10, Z01 ES071003] NR 38 TC 50 Z9 51 U1 0 U2 4 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 APR 15 PY 2008 VL 316 IS 2 BP 359 EP 370 DI 10.1016/j.ydbio.2008.01.042 PG 12 WC Developmental Biology SC Developmental Biology GA 286UF UT WOS:000254870800015 PM 18342849 ER PT J AU Nie, XG Deng, CX Wang, Q Jiao, K AF Nie, Xuguang Deng, Chu-xia Wang, Qin Jiao, Kai TI Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Smad4; pharyngeal arch; pharyngeal arch artery; outflow tract; facial primordia; neural crest cells ID DIGEORGE-SYNDROME PHENOTYPE; TRANSCRIPTION FACTOR AP-2; CONGENITAL HEART-DISEASE; OUTFLOW TRACT; MOUSE EMBRYOS; CARDIOVASCULAR DEFECTS; AORTIC-ARCH; TBX1; MICE; EXPRESSION AB TGF beta/BMP signaling pathways are essential for normal development of neural crest cells (NCCs). Smad4 encodes the only common Smad protein in mammals, which is a critical nuclear mediator of TGF/BMP signaling. In this work, we sought to investigate the roles of Smad4 for development of NCCs. To overcome the early embryonic lethality of Smad4 null mice, we specifically disrupted Smad4 in NCCs using a Cre/loxP system. The mutant mice died at mid-gestation with defects in facial primordia, pharyngeal arches, outflow tract and cardiac ventricles. Further examination revealed that mutant embryos displayed severe molecular defects starting from E9.5. Expression of multiple genes, including Msx1, 2, Ap-2 alpha, Pax3, and Sox9, which play critical roles for NCC development, was downregulated by NCC disruption of Smad4. Moreover, increased cell death was observed in pharyngeal arches from E10.5. However, the cell proliferation rate in these areas was not substantially altered. Taken together, these findings provide compelling genetic evidence that Smad4-mediated activities of TGF/BMP signals are essential for appropriate NCC development. (C) 2008 Elsevier Inc. All rights reserved. C1 [Nie, Xuguang; Jiao, Kai] Univ Alabama, Dept Genet, Div Genet & Translat Med, Birmingham, AL 35294 USA. [Deng, Chu-xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Wang, Qin] Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. RP Jiao, K (reprint author), Univ Alabama, Dept Genet, Div Genet & Translat Med, Birmingham, AL 35294 USA. EM kjiao@uab.edu RI deng, chuxia/N-6713-2016 FU NHLBI NIH HHS [1R21HL085510-01, R21 HL085510, R21 HL085510-01, R21 HL085510-02] NR 63 TC 30 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 APR 15 PY 2008 VL 316 IS 2 BP 417 EP 430 DI 10.1016/j.ydbio.2008.02.006 PG 14 WC Developmental Biology SC Developmental Biology GA 286UF UT WOS:000254870800020 PM 18334251 ER PT J AU Kwon, SY Xiao, H Glover, BP Tjian, R Wu, C Badenhorst, P AF Kwon, So Yeon Xiao, Hua Glover, Bradley P. Tjian, Robert Wu, Carl Badenhorst, Paul TI The nucleosome remodeling factor (NURF) regulates genes involved in Drosophila innate immunity SO DEVELOPMENTAL BIOLOGY LA English DT Article DE NURF; chromatin remodeling; JAK/STAT pathway; ISWI; Drosophila; innate immunity ID JAK/STAT SIGNALING COMPONENTS; IN-VIVO; CHROMATIN; EXPRESSION; ACTIVATION; SUBUNIT; COMPLEX; ISWI; TRANSCRIPTION; RECRUITMENT AB The Drosophila nucleosome remodeling factor (NURF) is an ISWI-containing chromatin remodeling complex that catalyzes ATP-dependent nucleosome sliding. By sliding nucleosomes, NURF has the ability to alter chromatin structure and regulate transcription. Previous studies have shown that mutation of Drosophila NURF induces melanotic tumors, implicating NURF in innate immune function. Here, we show that NURF mutants exhibit identical innate immune responses to gain-of-function mutants in the Drosophila JAK/STAT pathway. Using microarrays, we identify a common set of target genes that are activated in both mutants. In silico analysis of promoter sequences of these defines a consensus regulatory element comprising a STAT-binding sequence overlapped by a binding-site for the transcriptional repressor Ken. NURF interacts physically and genetically with Ken. Chromatin immunoprecipitation (ChIP) localizes NURF to Ken-binding sites in hemocytes, suggesting that Ken recruits NURF to repress STAT responders. Loss of NURF leads to precocious activation of STAT target genes. (c) 2008 Elsevier Inc. All rights reserved. C1 [Kwon, So Yeon; Badenhorst, Paul] Univ Birmingham, Inst Biomed Res, Edgbaston B15 2TT, England. [Xiao, Hua; Wu, Carl] NCI, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA. [Glover, Bradley P.; Tjian, Robert] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Badenhorst, P (reprint author), Univ Birmingham, Inst Biomed Res, Edgbaston B15 2TT, England. EM p.w.badenhorst@bham.ac.uk RI Kwon, So Yeon/M-5625-2014; OI Kwon, So Yeon/0000-0002-8490-9101; Badenhorst, Paul/0000-0002-2542-0250 FU Biotechnology and Biological Sciences Research Council [BB/D522470/1, ]; Intramural NIH HHS NR 39 TC 37 Z9 38 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 2008 VL 316 IS 2 BP 538 EP 547 DI 10.1016/j.ydbio.2008.01.033 PG 10 WC Developmental Biology SC Developmental Biology GA 286UF UT WOS:000254870800029 PM 18334252 ER PT J AU Wood, KC Hsu, LL Gladwin, MT AF Wood, Katherine C. Hsu, Lewis L. Gladwin, Mark T. TI Sickle cell disease vasculopathy: A state of nitric oxide resistance SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE hemolysis; reactive oxygen species; nitric oxide; vasculopathy; NADPH oxidase; xanthine oxidase; endothelium; nitric oxide resistance ID ACUTE CHEST SYNDROME; RED-BLOOD-CELLS; BONE-MARROW-TRANSPLANTATION; MAJOR PHYSIOLOGICAL CYTOPROTECTANT; SPONTANEOUSLY HYPERTENSIVE-RATS; CYCLOHYDROLASE-I OVEREXPRESSION; ADHESION MOLECULE EXPRESSION; ISCHEMIA-REPERFUSION INJURY; CARBON-MONOXIDE PRODUCTION; HEMOGLOBIN-SS DISEASE AB Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by microvascular vaso-occlusion with erythrocytes containing polymerized sickle (S) hemoglobin, erythrocyte hemolysis, vasculopathy, and both acute and chronic multiorgan injury. It is associated with steady state increases in plasma cell-free hemoglobin and overproduction of reactive oxygen species (ROS). Hereditary and acquired hemolytic conditions release into plasma hemoglobin and other erythrocyte components that scavenge endothelium-derived NO and metabolize its precursor arginine, impairing NO homeostasis. Overproduction of ROS, such as superoxide, by enzymatic (xanthine oxidase, NADPH oxidase, uncoupled eNOS) and nonenzymatic pathways (Fenton chemistry), promotes intravascular oxidant stress that can likewise disrupt NO homeostasis. The synergistic bioinactivation of NO by dioxygenation and oxidation reactions with cell-free plasma hemoglobin and ROS, respectively, is discussed as a mechanism for NO resistance in SCD vasculopathy. Human physiological and transgenic animal studies provide experimental evidence of cardiovascular and pulmonary resistance to NO donors and reduced NO bioavailability that is associated with vasoconstriction, decreased blood flow, platelet activation, increased endothelin-1 expression, and end-organ injury. Emerging epidemiological data now suggest that chronic intravascular hemolysis is associated with certain clinical complications: pulmonary hypertension, cutaneous leg ulcerations, priapism, and possibly stroke. New therapeutic strategies to limit intravascular hemolysis and ROS generation and increase NO bioavailability are discussed. Published by Elsevier Inc. C1 [Wood, Katherine C.; Gladwin, Mark T.] NHLBI, NIH, Vasc Med Branch, Bethesda, MD 20892 USA. [Hsu, Lewis L.] Drexel Univ, Coll Med, St Christophers Hosp Children, Marian Anderson Sickle Cell Ctr, Philadelphia, PA 19134 USA. [Gladwin, Mark T.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NHLBI, NIH, Vasc Med Branch, Bldg 10-CRC,Room 5-5140,10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA. EM mgladwin@nih.gov NR 291 TC 110 Z9 117 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 15 PY 2008 VL 44 IS 8 BP 1506 EP 1528 DI 10.1016/j.freeradbiomed.2008.01.008 PG 23 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 287OF UT WOS:000254925700002 PM 18261470 ER PT J AU Wang, H Ogawa, M Wood, JR Bartolomei, MS Sammel, MD Kusanovic, JP Walsh, SW Romero, R Strauss, JF AF Wang, Hongyan Ogawa, Masaki Wood, Jennifer R. Bartolomei, Marisa S. Sammel, Mary D. Kusanovic, Juan Pedro Walsh, Scott W. Romero, Roberto Strauss, Jerome F., III TI Genetic and epigenetic mechanisms combine to control MMP1 expression and its association with preterm premature rupture of membranes SO HUMAN MOLECULAR GENETICS LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISM; MATRIX-METALLOPROTEINASE; FETAL MEMBRANES; PROMOTER; CELLS; RISK; SNP; CANCER AB Degradation of fibrillar collagens is believed to be involved in the rupture of the fetal membranes during normal parturition and when the membranes rupture prematurely. Matrix metalloproteinase 1 (MMP1) is a key enzyme involved in extracellular matrix turnover, and genetic variation in the MMP1 promoter is associated with the risk of preterm premature rupture of membranes (PPROM). We determined whether epigenetic factors contribute to the control of MMP1 expression in the human amnion. Inhibition of DNA methylation with 5-aza-2'-deoxycytidine in amnion fibroblasts resulted in significantly increased MMP1 gene transcription, and an associated significant increase in MMP1 production. These effects were correlated with reduced DNA methylation at a particular site (-1538) in the MMP1 promoter. DNA methylation at this site in amnion was reduced in a larger percentage of fetal membranes that ruptured prematurely. A new T > C single nucleotide polymorphism (SNP) [AF007878.1 (MMP1):g.3447T>C] in the MMP1 promoter was also identified. The minor C allele was always methylated in vivo, and when methylated, resulted in increased affinity for a nuclear protein in amnion fibroblasts. The minor C allele had reduced promoter activity as assessed by plasmid transfection studies and chromatin immunoprecipitation assays using amnion fibroblasts heterozygous for the T > C SNP. In a case-control study, the minor C allele was found to be protective against PPROM, consistent with its reduced promoter function. We conclude that in addition to genetic variation, DNA methylation plays a role in controlling MMP1 expression and risk of an adverse obstetrical outcome. C1 [Walsh, Scott W.; Strauss, Jerome F., III] Virginia Commonwealth Univ, Dept Obstet & Gynecol, Richmond, VA 23298 USA. [Wang, Hongyan] Fudan Univ, Sch Life Sci, Inst Genet, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. [Ogawa, Masaki; Wood, Jennifer R.] Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. [Bartolomei, Marisa S.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Sammel, Mary D.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Kusanovic, Juan Pedro; Romero, Roberto] NICHD, Hutzel Hosp, Perinatol Res Branch, Detroit, MI 48201 USA. RP Strauss, JF (reprint author), Virginia Commonwealth Univ, Dept Obstet & Gynecol, MCV Campus,Sanger Hall,1st Floor,Room 1-071,1101, Richmond, VA 23298 USA. EM jfstrauss@vcu.edu FU Intramural NIH HHS; NICHD NIH HHS [R01 HD034612]; NIMHD NIH HHS [P60 MD002256] NR 12 TC 34 Z9 39 U1 0 U2 7 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 APR 15 PY 2008 VL 17 IS 8 BP 1087 EP 1096 DI 10.1093/hmg/ddm381 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 284LP UT WOS:000254708200003 PM 18178580 ER PT J AU Anderson, LA Engels, EA AF Anderson, Lesley A. Engels, Eric A. TI Hepatitis C virus infection and non-Hodgkin lymphoma: Interesting association or causal relationship? SO INTERNATIONAL JOURNAL OF CANCER LA English DT Editorial Material ID B-CELL LYMPHOMA; HEPATOCELLULAR-CARCINOMA; MIXED CRYOGLOBULINEMIA; METAANALYSIS; RISK; LYMPHOCYTES; PREVALENCE; COHORT; CD81 C1 [Anderson, Lesley A.; Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Anderson, Lesley A.] NCI, Off Preventat Oncol, Div Canc Prevent, Bethesda, MD 20892 USA. RP Engels, EA (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7076, Rockville, MD 20892 USA. EM engelse@mail.nih.gov OI Anderson, Lesley/0000-0002-1000-3649 NR 28 TC 8 Z9 8 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 APR 15 PY 2008 VL 122 IS 8 BP X EP XII DI 10.1002/ijc.23462 PG 3 WC Oncology SC Oncology GA 275JS UT WOS:000254068300001 PM 18271007 ER PT J AU Moore, LE Hung, R Karami, S Boffetta, P Berndt, S Hsu, CC Zaridze, D Janout, V Kollarova, H Bencko, V Navratilova, M Szeszenia-Dabrowska, N Mates, D Mukeria, A Holcatova, I Yeager, M Chanock, S Garcia-Closas, M Rothman, N Chow, WH Brennan, P AF Moore, Lee E. Hung, Rayjean Karami, Sara Boffetta, Paolo Berndt, Sonya Hsu, Charles C. Zaridze, David Janout, Vladimir Kollarova, Helen Bencko, Vladmir Navratilova, Marie Szeszenia-Dabrowska, N. Mates, Dana Mukeria, Anush Holcatova, Ivana Yeager, Meredith Chanock, Stephen Garcia-Closas, Montse Rothman, Nat Chow, Wong-Ho Brennan, Paul TI Folate metabolism genes, vegetable intake and renal cancer risk in central Europe SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE kidney cancer; folate metabolism; 1-C metabolism; TYMS; MTHFR; genetic susceptibility; diet; vegetable intake ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; ONE-CARBON METABOLISM; NON-HODGKIN-LYMPHOMA; THYMIDYLATE-SYNTHASE; BLADDER-CANCER; COMMON MUTATION; COLON-CANCER; POLYMORPHISMS; MTHFR; SUSCEPTIBILITY AB In a multicenter case-control study of renal cell carcinoma (RCC) conducted in central and eastern Europe, we reported a strong inverse association with high vegetable intake and RCC risk. The odds ratio (OR) for high compared to the lowest tertile of vegetable intake was OR = 0.67; (95% confidence interval (CI): 0.53-0.83; p-trend < 0.001). We hypothesized that variation in key folate metabolism genes may modify this association. Common variation in 5 folate metabolism genes (CBS: Ex9+33C > T (rs234706), Ex13 +41C > T (rs1801181), Ex18 -391 G > A (rs12613); MTHFR: A222V Ex5+79C > T (rs1801133), Ex8-62A > C (rs1801131); MTR: Ex26 20A > G (rs1805087), MTRR: Ex5+136 T > C (rs161870), and TYMS:IVS2-405 C > T (rs502396), Ex8+157 C > T (rs699517), Ex8 +227 A > G (rs2790)) were analyzed among 1,097 RCC cases and 1,555 controls geno-typed in this study. Having at least I variant T allele of MTHFR A222V was associated with higher RCC risk compared to those with 2 common (CC) alleles (OR = 1.44; 95% CI: 1.17-1.77; p = 0.001). After stratification by tertile of vegetable intake, the higher risk associated with the variant genotype was only observed in the low and medium tertiles (p-trend = 0.001), but not among those in the highest tertile (p-interaction = 0.22). The association remained robust after calculation of the false discovery rate (FDR = 0.05). Of the 3 TYMS SNPs examined, only the TYMS IVS2 -405 C (rs502396) variant was associated with a significantly lower risk compared to the common genotype (OR = 0.73; 95% CI: 0.570.93). Vegetable intake modified the association between all 3 TYMS SNPs and RCC risk (p-interaction < 0.04 for all). In summary, these findings suggest that common variation in MTHFR and TYMS genes may be associated with RCC risk, particularly when vegetable intake is low. (c) 2007 Wiley-Liss, Inc. C1 [Moore, Lee E.; Karami, Sara; Berndt, Sonya; Holcatova, Ivana; Garcia-Closas, Montse; Rothman, Nat; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Hung, Rayjean; Boffetta, Paolo; Hsu, Charles C.; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Hung, Rayjean] Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA. [Zaridze, David; Mukeria, Anush] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. [Janout, Vladimir; Kollarova, Helen] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic. [Janout, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic. [Navratilova, Marie] Masaryk Mem Canc Inst, Div Canc Epidemiol & Genet, Brno, Czech Republic. [Szeszenia-Dabrowska, N.] Inst Occupat Med, Dept Epidemiol, Lodz, Poland. [Mates, Dana] Inst Publ Hlth, Bucharest, Romania. [Yeager, Meredith; Chanock, Stephen] NCI, Dept Hlth & Human Serv, Core Genotyping Facil, Adv Technol Ctr,NIH, Bethesda, MD 20892 USA. RP Moore, LE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM moorele@mail.nih.gov RI Hung, Rayjean/A-7439-2013; Zaridze, David/K-5605-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; Garcia-Closas, Montserrat /F-3871-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; mates, dana/0000-0002-6219-9807 NR 28 TC 26 Z9 28 U1 0 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 APR 15 PY 2008 VL 122 IS 8 BP 1710 EP 1715 DI 10.1002/ijc.23318 PG 6 WC Oncology SC Oncology GA 275JS UT WOS:000254068300006 PM 18098291 ER PT J AU Velasco, A Corvalan, A Wistuba, II Riquelme, E Chuaqui, R Majerson, A Leach, FS AF Velasco, Alfredo Corvalan, Alejandro Wistuba, Ignacio I. Riquelme, Erick Chuaqui, Rodrigo Majerson, Alejandro Leach, Fredrick S. TI Mismatch repair expression in testicular cancer predicts recurrence and survival SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE mismatch repair; hMSH2; testicular cancer; microsatellite instability ID GERM-CELL TUMORS; MICROSATELLITE INSTABILITY; PROSTATE-CANCER; GENE-EXPRESSION; HMSH2; HMLH1; MUTATIONS AB We investigated mismatch repair (MMR) gene expression in testicular cancer as a molecular marker for clinical outcome (recurrence, response to chemotherapy and death) using protein expression and specific genetic alterations associated with the presence or absence of MMR activity. One hundred sixty-two cases of paraffin-embedded testis cancer specimens were subjected to immunohistochemical analysis using monoclonal antibody for MLH1 and MSH2 MMR proteins and genetic analysis using specific polymorphic markers. The degree of MMR immunoreactivity and genetic instability in the form of loss of heterozygosity (LOH) and/or microsatellite instability (MSI) were determined by comparing matched normal and tumor tissue. The degree of immunohistochemical staining for MMR expression was associated with a shorter time to tumor recurrence, resistance to chemotherapy and death. Furthermore, clinical relapse and cancer specific death was also associated with tumors exhibiting a high degree of MSI, p = 0.01 and 0.04, respectively. In contrast, LOH was not associated with recurrence, resistance to chemotherapy or death. Therefore, MMR expression defines testis cancers with distinct molecular properties and clinical behavior, such that tumors with decreased MMR immunostaining and/or increased frequency of MSI have a shorter time to recurrence and death despite chemotherapy. (c) 2007 Wiley-Liss, Inc. C1 [Velasco, Alfredo; Riquelme, Erick] Clin Santa Maria, Dept Urol, Santiago, Chile. [Velasco, Alfredo; Majerson, Alejandro] Pontificia Univ Catolica Chile, Dept Urol, Santiago, Chile. [Corvalan, Alejandro] Pontificia Univ Catolica Chile, Dept Pathol, Santiago, Chile. [Wistuba, Ignacio I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Wistuba, Ignacio I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Chuaqui, Rodrigo] NCI, Pathol Branch, Bethesda, MD 20892 USA. [Leach, Fredrick S.] Alpha Zeta BioMed, Sugar Land, TX USA. RP Velasco, A (reprint author), Clin Santa Maria, Dept Urol, Av Santa Maria, Santiago, Chile. EM avelasco@csm.cl FU NCI NIH HHS [P30 CA016672] NR 21 TC 31 Z9 31 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 APR 15 PY 2008 VL 122 IS 8 BP 1774 EP 1777 DI 10.1002/ijc.23291 PG 4 WC Oncology SC Oncology GA 275JS UT WOS:000254068300014 PM 18076065 ER PT J AU Hsing, AW Zhang, M Rashid, A McGlynn, KA Wang, BS Niwa, S Ortiz-Conde, BA Goedert, JJ Fraumeni, JF O'Brien, TR Gao, YT AF Hsing, Ann W. Zhang, Mingdong Rashid, Asif McGlynn, Katherine A. Wang, Bing-Shen Niwa, Shelley Ortiz-Conde, Betty A. Goedert, James J. Fraumeni, Joseph F., Jr. O'Brien, Thomas R. Gao, Yu-Tang TI Hepatitis B and C virus infection and the risk of biliary tract cancer: A population-based study in China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE biliary tract cancer; HBV; HCV; gallstones; china ID INTRAHEPATIC CHOLANGIOCARCINOMA; CARCINOMA; SHANGHAI AB Emerging data suggest that chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may also play a role in extrahepatic bile duct cancers. To test the HBV hypothesis, we examined the relationship of HBV/HCV infection with risks of biliary tract cancer and biliary stones in a population-based case-control study conducted in Shanghai, China. Standard assays were used to detect HBV surface antigen (HBsAg) and antibodies against HBV core antigen (anti-HBc) and hepatitis C virus (anti-HCV) in sera from 417 patients with biliary tract cancers, 517 with biliary stones, and 762 healthy controls randomly selected from the population. Unconditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for each disease type. HBsAg seroprevalence was 7.3% among population controls and 14.2% among patients with extrahepatic bile duct cancer, resulting in a 2.4-fold risk of extrahepatic bile duct cancer (95% CI 1.2-4.5). No association was found for cancers of the gallbladder (prevalence 8.2%) or the ampulla of Vater (6.1%), or for stones in the gallbladder (10.1%) or bile duct (9.3%). Further adjustment for education, smoking, body mass index, diabetes and gallstones did not materially change the results. Prevalence of HCV infection in this population was low (2%), limiting our ability to detect an association with biliary diseases. In Shanghai, an HBV endemic area, chronic HBV infection was associated with a 2.4-fold risk of extrahepatic bile duct cancer. These results should be confirmed in other populations with varying risks of HBV and HCV infection. (c) 2007 Wiley-Liss, Inc. C1 [Hsing, Ann W.; McGlynn, Katherine A.; Goedert, James J.; Fraumeni, Joseph F., Jr.; O'Brien, Thomas R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. [Zhang, Mingdong] Chinese Univ Hong Kong, Ctr Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China. [Rashid, Asif] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. [Wang, Bing-Shen] Shanghai Med Univ, Zhongshan Hosp, Dept Surg, Shanghai 200032, Peoples R China. [Niwa, Shelley] Westat Corp, Rockville, MD USA. [Ortiz-Conde, Betty A.] NCI Frederick, Viral Epidemiol Sect, AIDS Vaccine Program, SAIC Frederick, Frederick, MD USA. [Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 5024,MSC 7234,6120 Execut Blvd, Bethesda, MD 20852 USA. EM hsinga@mail.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 21 TC 47 Z9 50 U1 2 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 APR 15 PY 2008 VL 122 IS 8 BP 1849 EP 1853 DI 10.1002/ijc.23251 PG 5 WC Oncology SC Oncology GA 275JS UT WOS:000254068300024 PM 18076042 ER PT J AU McGlynn, KA Gridley, G Mellemkjaer, L Brinton, LA Anderson, KC Caporaso, NE Landgren, O Olsen, JH AF McGlynn, Katherine A. Gridley, Gloria Mellemkjaer, Lene Brinton, Louise A. Anderson, Kenneth C. Caporaso, Neil E. Landgren, Ola Olsen, Jorgen H. TI Risks of cancer among a cohort of 23,935 men and women with osteophorosis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE osteoporosis; age; breast cancer; endometrial cancer; prostate cancer; colorectal cancer; smoking; alcohol ID BONE-MINERAL DENSITY; MULTIPLE-MYELOMA CELLS; BREAST-CANCER; ENDOMETRIAL CANCER; PROSTATE-CANCER; POSTMENOPAUSAL WOMEN; HIP-FRACTURES; REDUCED RISK; OSTEOPOROTIC FRACTURES; CIGARETTE-SMOKING AB Low hormone levels among persons with osteoporosis may decrease risk of some cancers. Other osteoporosis risk factors, such as smoking and alcohol consumption, however, may increase risk. As these deleterious factors are more often associated with osteoporosis diagnosed prior to age 70 years, cancer risk may be higher in these younger persons than in the general population. To examine this hypothesis, a cohort study of 23,935 persons with osteoporosis was conducted in Denmark. Patients hospitalized with osteoporosis between 1978 and 1993 were identified in the Danish Inpatient Register. Linkage to the Danish Cancer Registry identified all cancer outcomes through 2003. Standardized incidence ratios (SIR) and 95% confidence intervals (95%CI) were calculated to compare cancer incidence in the cohort with that in the general population. Persons diagnosed prior to age 70 years were at increased cancer risk (women: SIR = 1.11, 95%CI = 1.04-1.19; men: SIR = 1.31, 95%CI = 1.13-1.50) due, in part, to increased risks of cancers of the buccal cavity, esophagus, liver, pancreas and lung. Persons diagnosed at ages 70 and older were at decreased risk (women: SIR = 0.91, 95%CI = 0.87-0.96; men: SIR = 0.89, 0.77-1.01) due, in part, to decreased risks of breast, endometrial, colon, rectal and brain cancers in women and prostate cancer in men. These results suggest that risk factors associated with earlier onset osteoporosis may be associated with increased risk of cancer. Conversely, factors associated with later onset osteoporosis may be related to a decreased risk of cancer. (c) 2007 Wiley-Liss, Inc. C1 [Mellemkjaer, Lene; Olsen, Jorgen H.] Inst Canc Epidemiol, Danish Canc Soc, Copenhagen, Denmark. [Anderson, Kenneth C.] Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP McGlynn, KA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, EPS Suite 550 6120 Execut Blvd, Rockville, MD 20852 USA. EM mcglynnk@mail.nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 48 TC 15 Z9 15 U1 0 U2 2 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 APR 15 PY 2008 VL 122 IS 8 BP 1879 EP 1884 DI 10.1002/ijc.23290 PG 6 WC Oncology SC Oncology GA 275JS UT WOS:000254068300029 PM 18074348 ER PT J AU Simon, R Zhang, X AF Simon, Richard Zhang, Xinan TI On the dynamics of breast tumor development in women carrying germline BRCA1 and BRCA2 mutations SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE breast cancer; oncogenesis; stochastic model ID STEM-CELLS; CANCER AB We used mathematical models to analyze the age-incidence curve of breast carcinoma for individuals carrying a germline mutation in the BRCA1 or BRCA2 gene locus. Although many genomic abnormalities have been identified in breast tumors, we found that a two-stage model fit the data well. A one-hit model was not, however, consistent with the data. The results supported the hypothesis that the first hit represents loss of the wild type BRCA1 or BRCA2 allele as this occurs at a rate very similar to that for loss of the wild-type RB allele in retinoblastoma. Loss of the wild-type BRCA1 or BRCA2 allele appears to destabilize the genome as the second event occurs at a much higher rate. The second event is "rate limiting" in the sense that its occurrence is constrained by the limited number of intermediate cells with doubly mutated BRCA1 or BRCA2 alleles. The second event may not be unique, however. Loss of the wild-type BRCA allele appears to result in an increased rate for subsequent genomic events. A second event increasing proliferation of the partially malignant intermediate clone may lead inexorably to production and selection of cells with additional mutations in genes that facilitate tumor progression. (c) 2007 Wiley-Liss, Inc. C1 [Simon, Richard] NCI, Biomet Res Branch, Bethesda, MD 20892 USA. [Zhang, Xinan] Cent China Normal Univ, Dept Chem, Wuhan 430079, Hubei, Peoples R China. RP Simon, R (reprint author), NCI, Biomet Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 13 TC 6 Z9 6 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 APR 15 PY 2008 VL 122 IS 8 BP 1916 EP 1917 DI 10.1002/ijc.23323 PG 2 WC Oncology SC Oncology GA 275JS UT WOS:000254068300035 PM 18098285 ER PT J AU Cannata, JM Williams, JA Zhou, QF Sun, L Shung, KK Yu, H Kim, ES AF Cannata, J. M. Williams, J. A. Zhou, Q. F. Sun, L. Shung, K. K. Yu, H. Kim, E. S. TI Self-focused ZnO transducers for ultrasonic biomicroscopy SO JOURNAL OF APPLIED PHYSICS LA English DT Article ID FILMS; FABRICATION; DESIGN AB A simple fabrication technique was developed to produce high frequency (100 MHz) self-focused single element transducers with sputtered zinc oxide (ZnO) crystal films. This technique requires the sputtering of a ZnO film directly onto a curved backing substrate. Transducers were fabricated by sputtering an 18 mu m thick ZnO layer on 2 mm diameter aluminum rods with ends shaped and polished to produce a 2 mm focus or f-number equal to one. The aluminum rod served a dual purpose as the backing layer and positive electrode for the resultant transducers. A 4 mu m Parylene matching layer was deposited on the transducers after housing and interconnect. This matching layer was used to protect the substrate and condition the transfer of acoustic energy between the ZnO film and the load medium. The pulse-echo response for a representative transducer was centered at 101 MHz with a -6 dB bandwidth of 49%. The measured two way insertion loss was 44 dB. A tungsten wire phantom and an adult zebrafish eye were imaged to show the capability of these transducers. (c) 2008 American Institute of Physics. C1 [Cannata, J. M.; Williams, J. A.; Zhou, Q. F.; Sun, L.; Shung, K. K.] Univ So Calif, Dept Biomed Engn, NIH, Res Ctr Med Ultrason Transducer Technol, Los Angeles, CA 90089 USA. [Yu, H.] Arizona State Univ, Dept Elect Engn, Sch Earth & Space Explorat, Tempe, AZ 85287 USA. [Kim, E. S.] Univ So Calif, Dept Elect Engn & Electrophys, Los Angeles, CA 90089 USA. RP Cannata, JM (reprint author), Univ So Calif, Dept Biomed Engn, NIH, Res Ctr Med Ultrason Transducer Technol, Los Angeles, CA 90089 USA. EM cannata@usc.edu RI SUN, Lei/G-3350-2014 OI SUN, Lei/0000-0001-7047-9529 FU NIBIB NIH HHS [P41 EB002182] NR 11 TC 10 Z9 10 U1 3 U2 14 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD APR 15 PY 2008 VL 103 IS 8 AR 084109 DI 10.1063/1.2907716 PG 4 WC Physics, Applied SC Physics GA 295DW UT WOS:000255456200123 PM 19479005 ER PT J AU Dey-Guha, I Malik, N Lesourne, R Love, PE Westphal, H AF Dey-Guha, Ipsita Malik, Nasir Lesourne, Renaud Love, Paul E. Westphal, Heiner TI Tyrosine phosphorylation controls nuclear localization and transcriptional activity of Ssdp1 in mammalian cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE Ssdp1; intracellular transport; LIM-HD complex; phosphorylation ID NUCLEOCYTOPLASMIC TRANSPORT; SIGNAL-TRANSDUCTION; PROTEINS; DOMAIN; COMPLEX; LDB1 AB The LIM-HD proteins interact with different cofactors, including Ssdp1 to regulate development in a diverse range of species. The single stranded DNA binding protein (Ssdp1) is a member of an evolutionarily conserved family of proteins that regulate critical transcriptional processes during embryonic development. Ssdp1 is localized predominantly in the cytoplasm of 293T cells but is translocated to the nucleus when co-transfected with Lck,a member of the Src family of non-receptor tyrosine kinases. The Srctyrosine kinase inhibitor PP2 blocked the nuclear translocation of Ssdp1. Western blot analysis showed that co-expression of Ssdp1 and Lck in 293T cells induces Ssdp1 phosphorylation. Mutation of the Ssdp1 N terminal tyrosine residues 23 and 25 markedly reduced both the phosphorylation and the nuclear localization of Ssdp1. Lck enhanced the transcriptional activity of Ssdp1 in the context of known components of a LIM-homeodomain (LIM-HD)/cofactor complex. We propose that phosphorylation involving N-terminal tyrosine residues of Ssdp1 is a means of regulating its nuclear localization and subsequent transcriptional activation of LIM-HD complexes. C1 [Dey-Guha, Ipsita; Malik, Nasir; Lesourne, Renaud; Love, Paul E.; Westphal, Heiner] NICHHD, Lab Mammalian Genes & Dev, NIH, HHS, Bethesda, MD 20892 USA. RP Westphal, H (reprint author), NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. EM hw@mail.nih.gov RI Lesourne, Renaud/M-1855-2014 FU Intramural NIH HHS NR 17 TC 2 Z9 2 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 15 PY 2008 VL 103 IS 6 BP 1856 EP 1865 DI 10.1002/jcb.21576 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 284AW UT WOS:000254678600016 PM 18080319 ER PT J AU Rachitskaya, AV Hansen, AM Horai, R Li, ZQ Villasmil, R Luger, D Nussenblatt, RB Caspi, RR AF Rachitskaya, Aleksandra V. Hansen, Anna M. Horai, Reiko Li, Zhuqing Villasmil, Rafael Luger, Dror Nussenblatt, Robert B. Caspi, Rachel R. TI Cutting edge: NKT cells constitutively express IL-23 receptor and ROR gamma t and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T(H)17; INFLAMMATION; POPULATION; PATHWAYS; GROWTH AB Th17 cells require IL-6 and TGF beta for lineage commitment and IL-23 for maintenance. Unexpectedly, naive IL-6(-/-) splenocytes stimulated with anti-CD3 and IL-23 produced normal amounts of IL-17 during the first 24 h of culture. These rapid IL-6-independent IL-17 producers were identified as predominantly DX5+ TCR beta(+) NKT cells, and a comparable response could be found using the invariant NKT-specific ligand a galactosylceramide. Human NKT cells also produced IL-17. NKT cells constitutively expressed IL-23R and ROR gamma t. Ligation of either TCR or IL-23R triggered IL-17 production and both together had a synergistic effect, suggesting independent but convergent pathways. IL-17 production was not restricted to a particular subset of NKT cells but they were NK1.1 negative. Importantly, in vivo administration of a galactosylceramide triggered a rapid IL-17 response in the spleen. These data suggest an important biological role for innate IL-17 production by NKT cells that is rapid and precedes the adaptive IL-17 response. C1 [Rachitskaya, Aleksandra V.; Hansen, Anna M.; Horai, Reiko; Li, Zhuqing; Villasmil, Rafael; Luger, Dror; Nussenblatt, Robert B.; Caspi, Rachel R.] NIH, NEI, Immunol Lab, Bethesda, MD 20892 USA. [Rachitskaya, Aleksandra V.] Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program, Bethesda, MD 20814 USA. RP Caspi, RR (reprint author), NIH, NEI, Immunol Lab, 10 Ctr Dr,10-10N222, Bethesda, MD 20892 USA. EM rcaspi@helix.NIH.gov FU Howard Hughes Medical Institute; Intramural NIH HHS [Z01 EY000184-25, Z99 EY999999] NR 13 TC 261 Z9 265 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2008 VL 180 IS 8 BP 5167 EP 5171 PG 5 WC Immunology SC Immunology GA 324GU UT WOS:000257506900003 PM 18390697 ER PT J AU Robertson, SJ Messer, RJ Carmody, AB Mittler, RS Burlak, C Hasenkrug, KJ AF Robertson, Shelly J. Messer, Ronald J. Carmody, Aaron B. Mittler, Robert S. Burlak, Christopher Hasenkrug, Kim J. TI CD137 costimulation of CD8(+) T cells confers resistance to suppression by virus-induced regulatory T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FRIEND RETROVIRUS INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; RESPONSES IN-VIVO; 4-1BB COSTIMULATION; DUAL COSTIMULATION; EFFECTOR FUNCTION; CLONAL EXPANSION; IMMUNE-RESPONSES; GAMMA-INTERFERON; TUMOR-IMMUNITY AB Chronic viral infections cause high levels of morbidity and mortality worldwide, making the development of effective therapies a high priority for improving human health. We have used mice infected with Friend virus as a model to study immunotherapeutic approaches to the cure of chronic retroviral infections. In chronic Friend virus infections CD4(+) T regulatory (Treg) cells suppress CD8(+) T cell effector functions critical for virus clearance. In this study, we demonstrate that immunotherapy with a combination of agonistic anti-CD137 Ab and virus-specific, TCR-transgenic CD8(+) T cells produced greater than 99% reductions of virus levels within 2 wk. In vitro studies indicated that the CD137-specific Ab rendered the CD8(+) T cells resistant to Treg cell-mediated suppression with no direct effect on the suppressive function of the Treg cells. By 2 weeks after transfer, the adoptively transferred CD8(+) T cells were lost, likely due to activation-induced cell death. The highly focused immunological pressure placed on the virus by the single specificity CD8(+) T cells led to the appearance of escape variants, indicating that broader epitope specificity will be required for long-term virus control. However, the results demonstrate a potent strategy to potentiate the function of CD8(+) T cells in the context of immunosuppressive Treg cells. C1 [Robertson, Shelly J.; Messer, Ronald J.; Carmody, Aaron B.; Burlak, Christopher; Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, NIH, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. [Mittler, Robert S.] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30329 USA. [Mittler, Robert S.] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30329 USA. RP Hasenkrug, KJ (reprint author), NIAID, Rocky Mt Labs, NIH, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM khasenkrug@nih.gov FU Intramural NIH HHS [Z01 AI000753-12] NR 61 TC 31 Z9 32 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2008 VL 180 IS 8 BP 5267 EP 5274 PG 8 WC Immunology SC Immunology GA 324GU UT WOS:000257506900013 PM 18390707 ER PT J AU Chandele, A Joshi, NS Zhu, JF Paul, WE Leonard, WJ Kaech, SM AF Chandele, Anmol Joshi, Nikhil S. Zhu, Jinfang Paul, William E. Leonard, Warren J. Kaech, Susan M. TI Formation of IL-7R alpha(high) and IL-7R alpha(low) CD8 T cells during infection is regulated by the opposing functions of GABP alpha and Gfi-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IL-7 RECEPTOR-ALPHA; ETS TRANSCRIPTION FACTORS; INTERLEUKIN-7 RECEPTOR; GENE-EXPRESSION; BINDING-PROTEIN; LYMPHOCYTE DEVELOPMENT; SELECTIVE EXPRESSION; CUTTING EDGE; MEMORY; DIFFERENTIATION AB IL-7 is essential for the survival of naive and memory T cells, and IL-7 receptor a-chain (IL-7R alpha) expression is dynamically regulated in activated CD8 T cells during acute viral and bacterial infections. Most virus-specific CD8 T cells become IL-7R alpha(low) and are relatively short-lived, but some escape IL-7R alpha repression (referred to as IL-711 alpha(high) memory precursor effector cells) and preferentially enter the memory CD8 T cell pool. How antiviral effector CD8 T cells regulate IL-7Ra expression in an "on and off" fashion remains to be characterized. During lymphocytic choriomeningitis virus infection, we found that opposing actions of the transcription factors GABP alpha (GA binding protein alpha) and Gfi-1 (growth factor independence 1) control IL-7R alpha expression in effector CD8 T cells. Specifically, GABPa was required for IL-7R alpha expression in memory precursor effector cells, and this correlated with hyperacetylation of the Il7ra promoter. In contrast, Gfi-1 was required for stable IL-7R alpha repression in effector CD8 T cells and acted by antagonizing GABP alpha binding and recruiting histone deacetylase 1, which deacetylated the Il7ra promoter. Thus, Il7ra promoter acetylation and activity was dependent on the reciprocal binding of GABP alpha and Gfi-1, and these data provide a biochemical mechanism for the generation of stable IL-7R alpha(high) and IL-7R alpha(low) states in virus-specific effector CD8 T cells. C1 [Chandele, Anmol; Joshi, Nikhil S.; Kaech, Susan M.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06511 USA. [Zhu, Jinfang; Paul, William E.] NIAID, Immunol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Leonard, Warren J.] NHLBI, Lab Mol Immunol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Kaech, SM (reprint author), Yale Univ, Sch Med, Dept Immunobiol, Anlyan Ctr S640,300 Cedar St, New Haven, CT 06511 USA. EM Susan.Kaech@yale.edu RI Zhu, Jinfang/B-7574-2012 FU Intramural NIH HHS [Z01 AI000926-05]; NIAID NIH HHS [R01 AI066232, R01 AI 066232-01] NR 59 TC 54 Z9 55 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 APR 15 PY 2008 VL 180 IS 8 BP 5309 EP 5319 PG 11 WC Immunology SC Immunology GA 324GU UT WOS:000257506900018 PM 18390712 ER PT J AU Agarwal, RK Horai, R Viley, AM Silver, PB Grajewski, RS Su, SB Yazdani, AT Zhu, W Kronenberg, M Murray, PJ Rutschman, RL Chan, CC Caspi, RR AF Agarwal, Rajeev K. Horai, Reiko Viley, Angelia M. Silver, Phyllis B. Grajewski, Rafael S. Su, Shao Bo Yazdani, Arrash T. Zhu, Wei Kronenberg, Mitchell Murray, Peter J. Rutschman, Robert L. Chan, Chi-Chao Caspi, Rachel R. TI Abrogation of anti-retinal autoimmunity in IL-10 transgenic mice due to reduced T cell priming and inhibition of disease effector mechanisms SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BINDING PROTEIN; CYTOKINE PRODUCTION; UVEITIS; UVEORETINITIS; INTERLEUKIN-10; EXPRESSION; MACROPHAGES; VIVO AB Experimental autoimmune uveitis (EAU) induced by immunization of animals with retinal Ags is a model for human uveitis. The immunosuppressive cytokine IL-10 regulates EAU susceptibility and may be a factor in genetic resistance to EAU. To further elucidate the regulatory role of endogenous IL-10 in the mouse model of EAU, we examined transgenic (Tg) mice expressing IL-10 either in activated T cells (inducible) or in macrophages (constitutive). These IL-10-Tg mice and non-Tg wild-type controls were immunized with a uveitogenic regimen of the retinal Ag interphotoreceptor retinoid-binding protein. Constitutive expression of IL-10 in macrophages abrogated disease and reduced Ag-specific immunological responses. These mice had detectable levels of IL-10 in sera and in ocular extracts. In contrast, expression of IL-10 in activated T cells only partially protected from EAU and marginally reduced Ag-specific responses. All IL-10-Tg lines showed suppression of Ag-specific effector cytokines. APC from Tg mice constitutively expressing IL-10 in macrophages exhibited decreased ability to prime naive T cells, however, Ag presentation to already primed T cells was not compromised. Importantly, IL-10-Tg mice that received interphotoreceptor retinoid-binding protein-specific uveitogenic T cells from wild-type donors were protected from EAU. We suggest that constitutively produced endogenous IL-10 ameliorates the development of EAU by suppressing de novo priming of Ag-specific T cells and inhibiting the recruitment and/or function of inflammatory leukocytes, rather than by inhibiting local Ag presentation within the eye. C1 [Agarwal, Rajeev K.; Horai, Reiko; Viley, Angelia M.; Silver, Phyllis B.; Grajewski, Rafael S.; Su, Shao Bo; Yazdani, Arrash T.; Zhu, Wei; Chan, Chi-Chao; Caspi, Rachel R.] NEI, Immunol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Kronenberg, Mitchell] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA. [Murray, Peter J.; Rutschman, Robert L.] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, Natl Inst Hlth, 10 Ctr Dr,10-10N222, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov FU Intramural NIH HHS [Z01 EY000184-25, Z99 EY999999] NR 31 TC 13 Z9 14 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2008 VL 180 IS 8 BP 5423 EP 5429 PG 7 WC Immunology SC Immunology GA 324GU UT WOS:000257506900030 PM 18390724 ER PT J AU Cecchinato, V Tryniszewska, E Ma, ZM Vaccari, M Boasso, A Tsai, WP Petrovas, C Fuchs, D Heraud, JM Venzon, D Shearer, GM Koup, RA Lowy, I Miller, CJ Franchini, G AF Cecchinato, Valentina Tryniszewska, Elzbieta Ma, Zhong Min Vaccari, Monica Boasso, Adriano Tsai, Wen-Po Petrovas, Constantinos Fuchs, Dietmar Heraud, Jean-Michel Venzon, David Shearer, Gene M. Koup, Richard A. Lowy, Israel Miller, Christopher J. Franchini, Genoveffa TI Immune activation driven by CTLA-4 blockade augments viral replication at mucosal sites in simian immunodeficiency virus infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; INTESTINAL LAMINA PROPRIA; SIV INFECTION; INDOLEAMINE 2,3-DIOXYGENASE; HIV-INFECTION; TRYPTOPHAN CATABOLISM; PERIPHERAL-BLOOD; GASTROINTESTINAL-TRACT; DISEASE PROGRESSION; SEVERE DEPLETION AB The importance of chronic immune activation in progression to AIDS has been inferred by correlative studies in HIV-infected individuals and in nonhuman primate models of SIV infection. Using the SIVmac251 macaque model, we directly address the impact of immune activation by inhibiting CTLA-4, an immunoregulatory molecule expressed on activated T cells and a subset of regulatory T cells. We found that CTLA-4 blockade significantly increased T cell activation and viral replication in primary SIVmac251 infection, particularly at mucosal sites, and increased IDO expression and activity. Accordingly, protracted treatment with anti-CTLA-4 Ab of macaques chronically infected with SIVmac251 decreased responsiveness to antiretroviral therapy and abrogated the ability of therapeutic T cell vaccines to decrease viral set point. These data provide the first direct evidence that immune activation drives viral replication, and suggest caution in the use of therapeutic approaches for HIV infection in vivo that increase CD4(+) T cell proliferation. C1 [Cecchinato, Valentina; Tryniszewska, Elzbieta; Vaccari, Monica; Tsai, Wen-Po; Heraud, Jean-Michel; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. [Boasso, Adriano; Shearer, Gene M.] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Tryniszewska, Elzbieta] Med Univ Bialystok, Dept Microbiol Diagnost, Bialystok, Poland. [Ma, Zhong Min; Miller, Christopher J.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Petrovas, Constantinos; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Fuchs, Dietmar] Innsbruck Med Univ, Div Biol Chem, Bioctr, Innsbruck, Austria. [Lowy, Israel] Medarex, Bloomsburg, NJ 08804 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, 9000 Rockville Pike,41-D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov RI HERAUD, Jean-Michel/O-1464-2013; OI HERAUD, Jean-Michel/0000-0003-1107-0859; Boasso, Adriano/0000-0001-9673-6319 FU Intramural NIH HHS [Z99 AI999999]; NCRR NIH HHS [P51 RR000164-420147] NR 56 TC 62 Z9 66 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2008 VL 180 IS 8 BP 5439 EP 5447 PG 9 WC Immunology SC Immunology GA 324GU UT WOS:000257506900032 PM 18390726 ER PT J AU Dunham, RM Cervasi, B Brenchley, JM Albrecht, H Weintrob, A Sumpter, B Engram, J Gordon, S Klatt, NR Frank, I Sodora, DL Douek, DC Paiardini, M Silvestri, G AF Dunham, Richard M. Cervasi, Barbara Brenchley, Jason M. Albrecht, Helmut Weintrob, Amy Sumpter, Beth Engram, Jessica Gordon, Shari Klatt, Nichole R. Frank, Ian Sodora, Donald L. Douek, Daniel C. Paiardini, Mirko Silvestri, Guido TI CD127 and CD25 expression defines CD4(+) T cell subsets that are differentially depleted during HIV infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; ALPHA-CHAIN CD127; IMMUNE ACTIVATION; SOOTY MANGABEYS; TYPE-1 INFECTION; INTERLEUKIN-7 RECEPTOR; DISEASE PROGRESSION; IN-VIVO; GASTROINTESTINAL-TRACT AB Decreased CD4(+) T cell counts are the best marker of disease progression during HIV infection. However, CD4(+) T cells are heterogeneous in phenotype and function, and it is unknown how preferential depletion of specific CD4+ T cell subsets influences disease severity. CD4(+) T cells can be classified into three subsets by the expression of receptors for two T cell-tropic cytokines, IL-2 (CD25) and IL-7 (CD127). The CD127(+)CD25(low/-) subset includes IL-2-producing naive and central memory T cells; the CD127(-)CD25(-) subset includes mainly effector T cells expressing perforin and IFN-gamma; and the CD127(low)CD25(high) subset includes FoxP3-expressing regulatory T cells. Herein we investigated how the proportions of these T cell subsets are changed during HIV infection. When compared with healthy controls, HIV-infected patients show a relative increase in CD4(+)CD127(-)CD25(-) T cells that is related to an absolute decline of CD4(+)CD127(+)CD25(low/-) T cells. Interestingly, this expansion of CD4(+)CD127(-) T cells was not observed in naturally SIV-infected sooty mangabeys. The relative expansion of CD4(+)CD127(-)CD25(-) T cells correlated directly with the levels of total CD4(+) T cell depletion and immune activation. CD4(+)CD127(-)CD25(-) T cells were not selectively resistant to HIV infection as levels of cell-associated virus were similar in all non-naive CD4(+) T cell subsets. These data indicate that, during HIV infection, specific changes in the fraction of CD4(+) T cells expressing CD25 and/or CD127 are associated with disease progression. Further studies will determine whether monitoring the three subsets of CD4(+) T cells defined based on the expression of CD25 and CD127 should be used in the clinical management of HIV-infected individuals. C1 [Silvestri, Guido] Univ Penn, Sch Med, Dept Pathol & Lab Med, Stellar Chance Labs 705, Philadelphia, PA 19104 USA. [Dunham, Richard M.; Sumpter, Beth; Gordon, Shari; Klatt, Nichole R.; Silvestri, Guido] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Dunham, Richard M.; Sumpter, Beth; Gordon, Shari; Klatt, Nichole R.; Silvestri, Guido] Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Brenchley, Jason M.; Douek, Daniel C.] NIAID, Human Immunol Lab, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. [Albrecht, Helmut; Weintrob, Amy] Crawford W Long Mem Hosp, Infect Dis Clin, Atlanta, GA 30308 USA. [Sodora, Donald L.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. RP Silvestri, G (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Stellar Chance Labs 705, 422 Curie Blvd, Philadelphia, PA 19104 USA. EM gsilvest@mail.med.upenn.edu RI Dunham, Richard/B-2012-2009; Albrecht, Helmut/D-5319-2011; Sumpter, Bobby/C-9459-2013 OI Dunham, Richard/0000-0003-4542-2330; Sumpter, Bobby/0000-0001-6341-0355 FU Intramural NIH HHS [Z99 AI999999]; NCRR NIH HHS [RR-00165, P51 RR000165]; NIAID NIH HHS [R01 AI052755, R01 AI066998, R01 AI52755, R01 AI66998] NR 90 TC 72 Z9 75 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2008 VL 180 IS 8 BP 5582 EP 5592 PG 11 WC Immunology SC Immunology GA 324GU UT WOS:000257506900049 PM 18390743 ER PT J AU Peters, NK Dixon, DM Holland, SM Fauci, AS AF Peters, N. Kent Dixon, Dennis M. Holland, Steven M. Fauci, Anthony S. TI The research agenda of the National Institute of Allergy and Infectious Diseases for antimicrobial resistance SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PANTON-VALENTINE LEUKOCIDIN; STAPHYLOCOCCUS-AUREUS; TUBERCULOSIS; DETERMINANT; VACCINE AB Antimicrobial resistance is an intrinsic and inevitable aspect of microbial survival that continually challenges human health. Research on antimicrobial resistance is central to the mission of the National Institute of Allergy and Infectious Diseases (NIAID). In fiscal year 2007, NIAID invested more than $800 million to support basic and translational research on antimicrobials, more than $200 million of which is devoted to understanding the causes, consequences, and treatments of antimicrobial drug resistance. The complex process that facilitates the transformation of ideas into therapies requires a pipeline that runs from bench to bedside, and NIAID has leveraged the entire spectrum of conventional and biodefense resources. NIAID works in partnership with other federal agencies, industry, foundation partners, and foreign governments. The basic and clinical research supported by NIAID will, ideally, continue to yield profound rewards in terms of the understanding, diagnosis, and treatment of infectious diseases. C1 [Peters, N. Kent; Dixon, Dennis M.; Holland, Steven M.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA. RP Peters, NK (reprint author), NIAID, NIH, 610 Rockledge Dr,MSC 6603, Bethesda, MD 20892 USA. EM kent.peters@nih.gov OI Peters, Norman/0000-0003-0795-1362 NR 25 TC 24 Z9 25 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2008 VL 197 IS 8 BP 1087 EP 1093 DI 10.1086/533451 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 288YE UT WOS:000255021400004 PM 18419527 ER PT J AU Mackelprang, RD John-Stewart, G Carrington, M Richardson, B Rowland-Jones, S Gao, X Mbori-Ngacha, D Mabuka, J Lohman-Payne, B Farquhar, C AF Mackelprang, Romel D. John-Stewart, Grace Carrington, Mary Richardson, Barbra Rowland-Jones, Sarah Gao, Xiaojiang Mbori-Ngacha, Dorothy Mabuka, Jennifer Lohman-Payne, Barbara Farquhar, Carey TI Maternal HLA homozygosity and mother-child HLA concordance increase the risk of vertical transmission of HIV-1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th Conference on Retroviruses and Opportunistic Infections CY FEB 25-28, 2007 CL Los Angeles, CA ID VIRUS TYPE-I; TYPE-1 TRANSMISSION; ASSOCIATION; INFECTION; RESPONSES; ALLELES AB Background. Mother-child human leukocyte antigen (HLA) concordance and maternal HLA homozygosity may increase the risk of vertical transmission of human immunodeficiency virus type 1 (HIV-1) risk by reducing infant immune responses. Methods. We analyzed mother-child HLA concordance and maternal HLA homozygosity in a Kenyan perinatal cohort receiving antenatal zidovudine. HLA concordance was scored as the number of shared class I alleles, and relative risk estimates were adjusted for maternal HIV-1 load. Results. Among 277 mother-infant pairs, HIV-1 transmission occurred in 58 infants (21%), with in utero transmission in 21 (36%), peripartum transmission in 26 (45%), and transmission via breast-feeding in 11 (19%). With increased concordance, we observed a significant increase in the risk of transmission overall (adjusted hazard ratio [aHR], 1.3 [95% confidence interval {CI}, 1.0-1.7]; P = .04), in utero (adjusted odds ratio, 1.72 [95% CI, 1.0-1.7]; P = .04), and via breast-feeding (aHR, 1.6 [95% CI, 1.0-2.5]; P = .04). Women with homozygosity had higher plasma HIV-1 RNA levels at 32 weeks of gestation (5.1 vs. 4.8 log(10) copies/mL; P = .03) and an increased risk of transmission overall (aHR, 1.7 [95% CI, 1.1-2.7]; P = .03) and via breast-feeding (aHR, 5.8 [95% CI, 1.9-17.7]; P = .002). Conclusion. The risks of overall, in utero, and breast milk HIV-1 transmission increased with HLA concordance and homozygosity. The increased risk may be due to reduced alloimmunity or less diverse protective immune responses. C1 [Mackelprang, Romel D.; John-Stewart, Grace; Farquhar, Carey] Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. [John-Stewart, Grace; Lohman-Payne, Barbara; Farquhar, Carey] Univ Washington, Dept Med, Seattle, WA 98104 USA. [Richardson, Barbra] Univ Washington, Dept Biostat, Seattle, WA 98104 USA. [Carrington, Mary; Gao, Xiaojiang] Sci Applicat Int Corp, Lab Genom Divers, Frederick, MD USA. [Carrington, Mary; Gao, Xiaojiang] NCI, Frederick, MD 21701 USA. [Mbori-Ngacha, Dorothy; Mabuka, Jennifer; Lohman-Payne, Barbara] Univ Nairobi, Dept Paediat, Nairobi, Kenya. [Rowland-Jones, Sarah] Weatherall Inst Mol Med, MRC, Human Immunol Unit, Oxford, England. RP Farquhar, C (reprint author), Univ Washington, Dept Epidemiol, 325 9th Ave,Box 359909, Seattle, WA 98104 USA. EM cfarq@u.washington.edu FU FIC NIH HHS [D43 TW000007, K01 TW006080, KO1 TW06080]; Intramural NIH HHS; Medical Research Council [MC_U137884180]; NCI NIH HHS [N01 CO012400, N01-CO-12400, N01CO12400]; NIAID NIH HHS [P30 AI027757]; NICHD NIH HHS [HD23412, K23 HD041879, K23 HD41879, K24 HD054314, K24 HD054314-03, R01 HD023412, R01 HD023412-15] NR 22 TC 36 Z9 37 U1 0 U2 2 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 APR 15 PY 2008 VL 197 IS 8 BP 1156 EP 1161 DI 10.1086/529528 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 288YE UT WOS:000255021400012 PM 18462163 ER PT J AU McDermott, MM Tian, L Liu, K Guralnik, JM Ferrucci, L Tan, J Pearce, WH Schneider, JR Criqui, MH AF McDermott, Mary M. Tian, Lu Liu, Kiang Guralnik, Jack M. Ferrucci, Luigi Tan, Jin Pearce, William H. Schneider, Joseph R. Criqui, Michael H. TI Prognostic value of functional performance for mortality in patients with peripheral artery disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LOWER-EXTREMITY FUNCTION; ANKLE-BRACHIAL INDEX; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE; DAILY-LIFE; ASSOCIATION; DISABILITY; CIRCULATION AB Objectives Among persons with lower extremity peripheral artery disease (PAD), we determined whether objective measures of walking performance predict mortality independently of the ankle brachial index (ABI). Background The ability of office-based functional performance measures to predict mortality in patients with PAD is unknown. Methods Participants were 444 persons with PAD followed prospectively for 4.8 years. The 6-min walk and 4-m walks at usual and fastest pace were measured at baseline. Cox proportional hazard models were used to assess relations between baseline measures of lower extremity performance with mortality, adjusting for confounders. Results One hundred twenty-seven patients (28.6%) died during follow-up. Adjusting for age, gender, race, comorbidities, ABI, and other confounders, participants in the poorest baseline quartile of 6-min walk performance had significantly increased total mortality (hazard ratio [HR] 2.36 [95% confidence interval (CI) 1.33 to 4.18]) and cardiovascular mortality (HR 5.59 [95% CI 1.97 to 15.9]) compared with the best quartile of baseline performance. Participants in the poorest baseline quartile of normai-paced 4-m walking speed had significantly increased total mortality (HR 1.86 [95% CI 1.06 to 3.29]) and cardiovascular mortality (HR 2.55 [95% CI 1.01 to 6.46]) compared with the best quartile of baseline performance. Conclusions This study demonstrates for the first time that performance-based measures, which can be administered in an office setting, provide prognostic information regarding mortality in persons with PAD beyond that provided by the ABI. C1 [McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [McDermott, Mary M.; Tian, Lu; Liu, Kiang; Tan, Jin] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Pearce, William H.; Schneider, Joseph R.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Schneider, Joseph R.] Evanston Northwestern Hosp, Dept Surg, Evanston, IL USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Ferrucci, Luigi] NIA, Lab Clin Epidemiol, Bethesda, MD 20892 USA. RP McDermott, MM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. FU Intramural NIH HHS; NCRR NIH HHS [RR-00048, M01 RR000048]; NHLBI NIH HHS [R01 HL058099, R01 HL058099-04, R01 HL064739, R01 HL064739-04, R01 HL071223, R01 HL076298, R01 HL076298-04, R01-HL071223, R01-HL076298, R01-HL58099, R01-HL64739] NR 18 TC 74 Z9 74 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 15 PY 2008 VL 51 IS 15 BP 1482 EP 1489 DI 10.1016/j.jacc.2007.12.034 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 288SX UT WOS:000255007200011 PM 18402904 ER PT J AU Selleri, S Deola, S Pos, Z Jin, P Worschech, A Slezak, SL Rumio, C Panelli, MC Maric, D Stroncek, DF Wang, E Marincola, FM AF Selleri, Silvia Deola, Sara Pos, Zoltan Jin, Ping Worschech, Andrea Slezak, Stefanie L. Rumio, Cristiano Panelli, Monica C. Maric, Dragan Stroncek, David F. Wang, Ena Marincola, Francesco M. TI GM-CSF/IL-3/IL-5 receptor common beta chain (CD131) expression as a biomarker of antigen-stimulated CD8(+) T cells SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID GM-CSF; TUMOR; LYMPHOCYTES; RESPONSES; EFFECTOR; IMMUNITY; SUBSETS AB Background: Upon Ag-activation cytotoxic T cells (CTLs) produce IFN-gamma GM-CSF and TNF-alpha, which deliver simultaneously pro-apoptotic and pro-inflammatory signals to the surrounding microenvironment. Whether this secretion affects in an autocrine loop the CTLs themselves is unknown. Methods: Here, we compared the transcriptional profile of Ag-activated, Flu-specific CTL stimulated with the FLU MI:58-66 peptide to that of convivial CTLs expanded in vitro in the same culture. PBMCs from 6 HLA-A*0201 expressing donors were expanded for 7 days in culture following Flu MI: 58-66 stimulation in the presence of 300 IU/ml of interleukin-2 and than sorted by high speed sorting to high purity CD8+ expressing T cells gated according to FluMI:58-66 tetrameric human leukocyte antigen complexes expression. Results: Ag-activated CTLs displayed higher levels of IFN-gamma, GM-CSF (CSF2) and GM-CSF/IL-3/IL-5 receptor common beta-chain (CD131) but lacked completely expression of IFN-gamma receptor-II and IFN-stimulated genes (ISGs). This observation suggested that Ag-activated CTLs in preparation for the release of IFN-gamma and GM-CSF shield themselves from the potentially apoptotic effects of the former entrusting their survival to GM-SCF. In vitro phenotyping confirmed the selective surface expression of CD131 by Ag-activated CTLs and their increased proliferation upon exogenous administration of GM-CSF. Conclusion: The selective responsiveness of Ag-activated CTLs to GM-CSF may provide an alternative explanation to the usefulness of this chemokine as an adjuvant for T cell aimed vaccines. Moreover, the selective expression of CD131 by Ag-activated CTLs proposes CD131 as a novel biomarker of Ag-dependent CTL activation. C1 [Selleri, Silvia; Pos, Zoltan; Jin, Ping; Worschech, Andrea; Wang, Ena; Marincola, Francesco M.] NIH, Ctr Clin, Dept Transfus Med, IDIS, Bethesda, MD 20892 USA. [Selleri, Silvia; Deola, Sara] Sci Inst HS Raffaele, Hematol & BMT Unit, Milan, Italy. [Slezak, Stefanie L.; Stroncek, David F.] NIH, Ctr Clin, Dept Transfus Med, Cell Proc Sect, Bethesda, MD 20892 USA. [Rumio, Cristiano] Univ Milan, Dept Human Morphol, Milan, Italy. [Panelli, Monica C.] Univ Pittsburgh, Dept Med, Ctr Canc, Pittsburgh, PA USA. [Maric, Dragan] NIH, NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Ctr Clin, Dept Transfus Med, IDIS, Bethesda, MD 20892 USA. EM silvia.selleri@unimi.it; deola.sara@hsr.it; posz@cc.nih.gov; jinp@cc.nih.gov; worschecha@cc.nih.gov; SSlezak@cc.nih.gov; cristiano.rumio@unimi.it; panellim@upmc.edu; MaricD@ninds.nih.gov; DStroncek@cc.nih.gov; EWang@mail.cc.nih.gov; FMarincola@mail.cc.nih.gov RI Worschech, Andrea/I-3919-2012; Pos, Zoltan/C-3623-2014 OI Worschech, Andrea/0000-0002-4303-8653; Pos, Zoltan/0000-0002-2574-7616 NR 22 TC 12 Z9 12 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD APR 15 PY 2008 VL 6 AR 17 DI 10.1186/1479-5876-6-17 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 292QA UT WOS:000255280000001 PM 18412971 ER PT J AU Xu, Y Valentino, DJ Scher, AI Dinov, I White, LR Thompson, PM Launer, LJ Toga, AW AF Xu, Yuan Valentino, Daniel J. Scher, Ann I. Dinov, Ivo White, Lon R. Thompson, Paul M. Launer, Lenore J. Toga, Arthur W. TI Age effects on hippocampal structural changes in old men: The HAAS SO NEUROIMAGE LA English DT Article DE statistical shape analysis; age; hippocampus; Alzheimer's disease; vascular dementia ID MILD COGNITIVE IMPAIRMENT; WHITE-MATTER LESIONS; AUTOMATED IMAGE REGISTRATION; ISCHEMIC VASCULAR DEMENTIA; MEDIAL TEMPORAL-LOBE; ALZHEIMERS-DISEASE; ENTORHINAL CORTEX; CEREBROVASCULAR-DISEASE; MEMORY PERFORMANCE; LONGITUDINAL MRI AB Understanding the variability of the hippocampus in human brain research is essential. The effect of age on the hippocampus has been explored in several studies that have been focused on either normal aging or neural degeneration. Shape analysis of magnetic resonance imaging (MRI) provides morphological measures for brain structures. This study further investigates the age effects on hippocampal morphology in three groups (104 normal controls, 24 Alzheimer's disease (AD) and 14 vascular dementia (VaD) patients). By utilizing a parametric shape analysis of hippocampal MRI scans, each individual distance map is generated and analyzed statistically. Specifically, after eliminating similarity parameters (rotation, translation, and scaling) effects for each hippocampus, an individual distance map is generated from parametric hippocampal surfaces and medial axes. Then statistical methods, including regression, and permutation tests, are applied to detect the differences in hippocampal distance maps and volumes under the effect of age in each group. Statistical analyses reveal that the loss of hippocampal volume and changes in shape are more significantly related to aging in the control group than in AD/VaD. The results also show that the asymmetry of hippocampus in healthy subjects is greater than that in either of the disease groups. Our study shows that 3D statistical shape analysis could enhance the understanding of age effects on local areas of hippocampi. However, the sample sizes of disease groups are relatively low; further studies with more AD/VaD data are needed. (C) 2008 Published by Elsevier Inc. C1 [Xu, Yuan; Valentino, Daniel J.; Dinov, Ivo; Thompson, Paul M.; Toga, Arthur W.] Univ Calif Los Angeles, Sch Med, Lab Neuro Imaging, Dept Neurol, Los Angeles, CA 90095 USA. [Scher, Ann I.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Scher, Ann I.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [White, Lon R.] Pacific Hlth Res Inst, Honolulu, HI USA. RP Valentino, DJ (reprint author), Univ Calif Los Angeles, Sch Med, Lab Neuro Imaging, Dept Neurol, Mail Stop 172115, Los Angeles, CA 90095 USA. EM daniel.valentino@gmail.com OI Dinov, Ivo/0000-0003-3825-4375 FU Intramural NIH HHS; NCRR NIH HHS [P41 RR013642-10, U54 RR021813-01, P41 RR013642, P41 RR013642-09, U54 RR021813, U54 RR021813-010001]; NIA NIH HHS [U01 AG019349-08, U01 AG019349-05, U01 AG019349, R01 AG0-17155S1, R01 AG017155]; NIBIB NIH HHS [P01 EB001955-15, P01 EB001955]; NIMH NIH HHS [R01 MH071940-04, R01 MH071940, R01 MH071940-05] NR 73 TC 24 Z9 25 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2008 VL 40 IS 3 BP 1003 EP 1015 DI 10.1016/j.neuroimage.2007.12.034 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 284TH UT WOS:000254728200002 PM 18280181 ER PT J AU Paisan-Ruiz, C Dogu, O Yilmaz, A Houlden, H Singleton, A AF Paisan-Ruiz, C. Dogu, O. Yilmaz, A. Houlden, H. Singleton, A. TI SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia SO NEUROLOGY LA English DT Article ID THIN CORPUS-CALLOSUM AB Background: Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common form of complex hereditary spastic paraplegia. The genetic lesion underlying ARHSP-TCC was localized to chromosome 15q13-q15 and given the designation SPG11. Recently, the gene encoding spatacsin (KIAA1840) has been shown to contain mutations that underlie the majority of ARHSP-TCC cases. Methods: We present a complete analysis of the 40 coding exons of this gene in patients with sporadic (n = 25) or familial (20 probands) complex hereditary spastic paraplegia with and without thinning of the corpus callosum. Results: We identified seven mutations, including deletions, insertions, and nonsense mutations, which were all predicted to lead to premature truncation of the protein. Conclusion: We conclude that mutations on KIAA1840 are frequent in complex autosomal recessive hereditary spastic paraplegia but an infrequent cause of sporadic complex hereditary spastic paraplegia. C1 [Paisan-Ruiz, C.; Singleton, A.] NIA, Mol Genet Unit, NIH, Bethesda, MD 20824 USA. [Dogu, O.; Yilmaz, A.] Mersin Univ, Fac Med, Dept Neurol, Mersin, Turkey. [Houlden, H.] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. RP Paisan-Ruiz, C (reprint author), NIA, Mol Genet Unit, NIH, 35 Lincoln Dr,Bldg 35,Room 1A1015, Bethesda, MD 20824 USA. EM C.Paisan-Ruiz@ion.ucl.ac.uk RI Houlden, Henry/C-1532-2008; Paisan-Ruiz, Coro/C-2912-2009; Singleton, Andrew/C-3010-2009; Dogu, Okan/A-2045-2010 OI Houlden, Henry/0000-0002-2866-7777; FU Intramural NIH HHS [Z01 AG000957-05]; Medical Research Council [, G108/638]; NIA NIH HHS [Z01 AG000957] NR 7 TC 40 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 15 PY 2008 VL 70 IS 16 BP 1384 EP 1389 DI 10.1212/01.wnl.0000294327.66106.3d PN 2 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 312XW UT WOS:000256706700004 PM 18337587 ER PT J AU Dimyan, MA Dobkin, BH Cohen, LG AF Dimyan, Michael A. Dobkin, Bruce H. Cohen, Leonardo G. TI Emerging subspecialties: Neurorehabilitation - Training neurologists to retrain the brain SO NEUROLOGY LA English DT Editorial Material ID REHABILITATION; STROKE C1 NINDS, Med Neurol Branch, Human Cort Physiol Sect, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Brain Res Inst, Los Angeles, CA 90095 USA. RP Dimyan, MA (reprint author), 10 Ctr Dr,10-5N234 MSC1428, Bethesda, MD 20892 USA. EM dimyanm@mail.nih.gov RI Dimyan, Michael/B-1715-2012; OI Dimyan, Michael/0000-0002-9715-9741 FU NICHD NIH HHS [R24 HD039629]; NINDS NIH HHS [T32 NS007479] NR 9 TC 9 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 15 PY 2008 VL 70 IS 16 BP E52 EP E54 DI 10.1212/01.wnl.0000309216.81257.3f PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 312XV UT WOS:000256706600020 PM 18413581 ER PT J AU Lin, P Batra, VK Pedersen, LC Beard, WA Wilson, SH Pedersen, LG AF Lin, Ping Batra, Vinod K. Pedersen, Lars C. Beard, William A. Wilson, Samuel H. Pedersen, Lee G. TI Incorrect nucleotide insertion at the active site of a G : A mismatch catalyzed by DNA polymerase beta SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE combined quantum mechanics and molecular mechanics; incorrect nucleotide incorporation; nucleotidyl transfer; two-stage mechanism ID PARTICLE MESH EWALD; REPLICATION FIDELITY; MOLECULAR-DYNAMICS; INITIO QM/MM; BETA; SPECIFICITY; MECHANISM; CORRECT; STATE; CHECKPOINTS AB Based on a recent ternary complex crystal structure of human DNA polymerase beta with a G:A mismatch in the active site, we carried out a theoretical investigation of the catalytic mechanism of incorrect nucleotide incorporation using molecular dynamics simulation, quantum mechanics, combined quantum mechanics, and molecular mechanics methods. A two-stage mechanism is proposed with a nonreactive active-site structural rearrangement prechemistry step occurring before the nucleotidyl transfer reaction. The free energy required for formation of the prechemistry state is found to be the major factor contributing to the decrease in the rate of incorrect nucleotide incorporation compared with correct insertion and therefore to fidelity enhancement. Hence, the transition state and reaction barrier for phosphodiester bond formation after the prechemistry state are similar to that for correct insertion reaction. Key residues that provide electrostatic stabilization of the transition state are identified. C1 [Lin, Ping; Pedersen, Lee G.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Batra, Vinod K.; Pedersen, Lars C.; Beard, William A.; Wilson, Samuel H.; Pedersen, Lee G.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Pedersen, LG (reprint author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA. EM lee_pedersen@unc.edu RI Pedersen, Lee/E-3405-2013; Lin, Ping/C-7115-2008 OI Pedersen, Lee/0000-0003-1262-9861; Lin, Ping/0000-0003-1200-4423 FU Intramural NIH HHS; NCI NIH HHS [1U19CA105010, U19 CA105010]; NHLBI NIH HHS [HL-06350, P01 HL006350] NR 41 TC 34 Z9 34 U1 0 U2 8 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 APR 15 PY 2008 VL 105 IS 15 BP 5670 EP 5674 DI 10.1073/pnas.0801257105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291ZX UT WOS:000255237200005 PM 18391201 ER PT J AU Son, SY Ma, A Kondou, Y Yoshimura, M Yamashita, E Tsukihara, T AF Son, Se-Young Ma, Achun Kondou, Youhei Yoshimura, Masato Yamashita, Eiki Tsukihara, Tomitake TI Structure of human monoamine oxidase A at 2.2-angstrom resolution: The control of opening the entry for substrates/inhibitors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE single transmembrane helix; transmembrane helical anchor; harmine; x-ray structure ID MACROMOLECULAR STRUCTURES; CRYSTALLOGRAPHY; INSIGHTS; PROGRAM; SUITE AB The mitochondrial outer membrane-anchored monoamine oxidase (MAO) is a biochemically important flavoenzyme that catalyzes the deamination of biogenic and xenobiotic amines. Its two subtypes, MAOA and MAOB, are linked to several psychiatric disorders and therefore are interesting targets for drug design. To understand the relationship between structure and function of this enzyme, we extended our previous low-resolution rat MAOA structure to the high-resolution wild-type and G110A mutant human MAOA structures at 2.2 and 2.17 angstrom, respectively. The high-resolution MAOA structures are similar to those of rat MAOA and human MAOB, but different from the known structure of human MAOA [De Colibus L, et al. (2005) Proc Natl Acad Sci USA 102:12684-12689], specifically regarding residues 108-118 and 210-216, which surround the substrate/inhibitor cavity. The results confirm that the inhibitor selectivity of MAOA and MAOB is caused by the structural differences arising from Ile-335 in MAOA vs. Tyr-326 in MAOB. The structures exhibit a C-terminal transmembrane helix with clear electron density, as is also seen in rat MAOA. Mutations on one residue of loop 108-118, G110, which is far from the active center but close to the membrane surface, cause the solubilized enzyme to undergo a dramatic drop in activity, but have less effect when the enzyme is anchored in the membrane. These results suggest that the flexibility of loop 108-118, facilitated by anchoring the enzyme into the membrane, is essential for controlling substrate access to the active site. We report on the observation of the structure-function relationship between a transmembrane helical anchor and an extra-membrane domain. C1 [Son, Se-Young; Yoshimura, Masato; Yamashita, Eiki; Tsukihara, Tomitake] Osaka Univ, Inst Prot Res, Lab Prot Crystallog, Suita, Osaka 5650871, Japan. [Ma, Achun] NIH, Cell Biol Lab, Canc Res Ctr, Natl Canc Inst, Bethesda, MD 20892 USA. [Kondou, Youhei] Kobe Univ, Grad Sch Med, Dept Physiol & Cell Biol, Chuo Ku, Kobe, Hyogo 6500017, Japan. RP Tsukihara, T (reprint author), Osaka Univ, Inst Prot Res, Lab Prot Crystallog, Yamadaoka 3-2,Suita, Suita, Osaka 5650871, Japan. EM tsuki@protein.osaka-u.ac.jp NR 26 TC 194 Z9 200 U1 3 U2 14 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 APR 15 PY 2008 VL 105 IS 15 BP 5739 EP 5744 DI 10.1073/pnas.0710626105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291ZX UT WOS:000255237200018 PM 18391214 ER PT J AU Alphs, HH Gambhira, R Karanam, B Roberts, JN Jagu, S Schiller, JT Zeng, WG Jackson, DC Roden, RBS AF Alphs, Hannah H. Gambhira, Ratish Karanam, Balasubramanyarn Roberts, Jeffrey N. Jagu, Subhashini Schiller, John T. Zeng, Weiguang Jackson, David C. Roden, Richard B. S. TI Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MINOR CAPSID PROTEIN; GLOBAL CANCER STATISTICS; PARTICLE VACCINE; CERVICAL-CANCER; YOUNG-WOMEN; TYPE-16; IMMUNIZATION; PEPTIDE; TRIAL; CLASSIFICATION AB Persistent infection with the high-risk subset of genitotropic human papillomavirus (HPV) genotypes is a necessary cause of cervical cancer. Given the global burden of cervical cancer, a low-cost, broadly protective vaccine is needed. RG-1 is a cross-neutralizing and protective monoclonal antibody that recognizes residues 17-36 of HPV16 minor capsid protein L2. Because this epitope is highly conserved in divergent HPV types, we determined whether vaccination with HPV16 L2 17-36 peptide is broadly protective. The peptide was administered to BALB/c mice three times at monthly intervals, either alone or in the context of a synthetic lipopeptide vaccine candidate (P25-P2C-HPV) produced by linkage of the HPV peptide with a broadly recognized T helper epitope (P25) and the Toll-like receptor-2 (TLR2) ligand dipalmitoyl-S-glyceryl cysteine (P2C). In contrast to vaccination with the L2 17-36 peptide or P25-P2C alone, a potent L2-specific antibody response was generated to the P25-P2C-HPV lipopeptide when delivered either s.c. or intranasally. Sera from mice vaccinated with the P25-P2C-HPV lipopeptide neutralized not only HPV16 pseudovirions but also other evolutionarily divergent oncogenic genital (HPV18, HPV45) and cutaneous (HPV5, BPV1) types. The L2-specific antibody response depended on MHC class 11, CD40, and MyD88 signaling. Additionally, vaccination with the P25-P2C-HPV lipopeptide protected mice from homologous challenge with HPV16 pseudovirions at cutaneous and genital sites and heterologous challenge with HPV45 pseudovirions. If provided in the appropriate context, therefore, HPV16 L2 17-36 might be used in a totally synthetic cross-protective HPV vaccine. C1 [Alphs, Hannah H.; Gambhira, Ratish; Karanam, Balasubramanyarn; Jagu, Subhashini; Roden, Richard B. S.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21231 USA. [Roden, Richard B. S.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21231 USA. [Roden, Richard B. S.] Johns Hopkins Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21231 USA. [Roberts, Jeffrey N.; Schiller, John T.] NCI, Bethesda, MD 20892 USA. [Zeng, Weiguang; Jackson, David C.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia. [Zeng, Weiguang; Jackson, David C.] VacTX Pty Ltd, Melbourne, Vic 3000, Australia. RP Roden, RBS (reprint author), Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21231 USA. EM roden@jhmi.edu OI Jackson, David/0000-0001-7255-270X FU Howard Hughes Medical Institute; Intramural NIH HHS; NCI NIH HHS [R01 CA118790, P50 CA098252] NR 34 TC 87 Z9 91 U1 0 U2 6 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 APR 15 PY 2008 VL 105 IS 15 BP 5850 EP 5855 DI 10.1073/pnas.0800868105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291ZX UT WOS:000255237200037 PM 18413606 ER PT J AU Sengupta, S den Boon, JA Chen, IH Newton, MA Stanhope, SA Cheng, YJ Chen, CJ Hildesheim, A Sugden, B Ahlquist, P AF Sengupta, Srikumar den Boon, Johan A. Chen, I-How Newton, Michael A. Stanhope, Stephen A. Cheng, Yu-Juen Chen, Chien-Jen Hildesheim, Allan Sugden, Bill Ahlquist, Paul TI MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microarray; collagen; metastasis; miRNA ID CHRONIC LYMPHOCYTIC-LEUKEMIA; COLLAGEN TYPE-I; BREAST-CANCER; PANCREATIC-CANCER; THYROID-CARCINOMA; GENE-EXPRESSION; MELANOMA-CELLS; METASTASIS; PROLIFERATION; LET-7 AB Using highly sensitive microarray-based procedures, we identified eight microRNAs (miRNAs) showing robust differential expression between 31 laser-capture-microdissected nasopharyngeal carcinomas (NPCs) and 10 normal healthy nasopharyngeal epithelial samples. in particular, miRNA mir-29c was expressed at one-fifth the levels in tumors as in normal epithelium. In NPC tumors, the lower mir-29c levels correlated with higher levels of multiple mRNAs whose 3' UTRs can bind mir-29c at target sequences conserved across many vertebrates. In cultured cells, introduction of mir-29c down-regulated these genes at the level of mRNA and inhibited expression of luciferase encoded by vectors having the 3' UTRs of these genes. Moreover, for each of several genes tested, mutating the mir-29c target sites in the 3' UTR abrogated mir-29c-induced inhibition of luciferase expression. Most of the mir-29c-targeted genes identified encode extracellular matrix proteins, including multiple collagens and laminin gamma(1), that are associated with tumor cell invasiveness and metastatic potential, prominent characteristics of NPC. Thus, we identify eight miRNAs differentially expressed in NPC and demonstrate the involvement of one in regulating genes involved in metastasis. C1 [Sengupta, Srikumar; den Boon, Johan A.; Ahlquist, Paul] Univ Wisconsin, Inst Mol Virol, Madison, WI 53076 USA. [Ahlquist, Paul] Univ Wisconsin, Howard Hughes Med Inst, Madison, WI 53076 USA. [Sengupta, Srikumar; den Boon, Johan A.; Sugden, Bill; Ahlquist, Paul] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53076 USA. [Newton, Michael A.; Stanhope, Stephen A.] Univ Wisconsin, Dept Stat, Madison, WI 53076 USA. [Newton, Michael A.; Stanhope, Stephen A.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53076 USA. [Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Chen, I-How; Cheng, Yu-Juen] Chang Gung Mem Hosp, Taipei 105, Taiwan. [Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan. RP Ahlquist, P (reprint author), Univ Wisconsin, Inst Mol Virol, Madison, WI 53076 USA. EM ahlquist@wisc.edu RI Chen, Chien-Jen/C-6976-2008; Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU Howard Hughes Medical Institute; NCI NIH HHS [P01 CA022443, CA22443, CA64364, CA97944, R01 CA064364, R01 CA097944, R29 CA064364] NR 46 TC 272 Z9 295 U1 3 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 APR 15 PY 2008 VL 105 IS 15 BP 5874 EP 5878 DI 10.1073/pnas.0801130105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291ZX UT WOS:000255237200041 PM 18390668 ER PT J AU Rana, ZA Gundersen, K Buonanno, A AF Rana, Zaheer A. Gundersen, Kristian Buonanno, Andres TI Activity-dependent repression of muscle genes by NFAT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE exercise; fiber type; plasticity; troponin ID MYOSIN HEAVY-CHAIN-2 GENE; I SLOW GENE; SKELETAL-MUSCLE; FIBER-TYPE; SELECTIVE INNERVATION; ELECTRICAL-ACTIVITY; TRANSGENIC MICE; CYCLOSPORINE-A; NERVE ACTIVITY; RAT MUSCLES AB Adult skeletal muscles retain an adaptive capacity to switch between slow- and fast-twitch properties that largely depend on motoneuron activity. The NFAT (nuclear factor of activated T cells) family of calcium-dependent transcription factors has been implicated in the up-regulation of genes encoding slow contractile proteins in response to slow-patterned motoneuron depolarization. Here, we demonstrate an unexpected, novel function of NFATc1 in slow-twitch muscles. Using the troponin I fast (TnIf) intronic regulatory element (FIRE), we identified sequences that down-regulate its function selectively in response to patterns of electrical activity that mimic slow motoneuron firing. A bona fide NFAT binding site in the TnIf FIRE was identified by site-directed mutations and by electrophoretic mobility and supershift assays. The activity-dependent transcriptional repression of FIRE is mediated through this NFAT site and, importantly, its mutation did not alter. the up-regulation of TnIf transcription by fast-patterned activity. siRNA-mediated knockdown of NFATc1 in adult muscles resulted in ectopic activation of the FIRE in the slow soleus, without affecting enhancer activity in the fast extensor digitorum longus muscle. These findings demonstrate that NFAT can function as a repressor of fast contractile genes in slow muscles and they exemplify how an activity pattern can increase or decrease the expression of distinct contractile genes in a use-dependent manner as to enhance phenotypic differences among fiber types or induce adaptive changes in adult muscles. C1 [Rana, Zaheer A.; Buonanno, Andres] NICHHD, Mol Neurobiol Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Rana, Zaheer A.; Gundersen, Kristian] Univ Oslo, Dept Mol Biosci, N-0316 Oslo, Norway. RP Buonanno, A (reprint author), NICHHD, Mol Neurobiol Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. EM buonanno@helix.nih.gov NR 54 TC 27 Z9 27 U1 1 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 APR 15 PY 2008 VL 105 IS 15 BP 5921 EP 5926 DI 10.1073/pnas.0801330105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 291ZX UT WOS:000255237200049 PM 18408153 ER PT J AU Bonnot, O Tanguy, ML Consoli, A Comic, F Graindorge, C Laurent, C Tordjman, S Cohen, D AF Bonnot, Olivier Tanguy, Marie-Laure Consoli, Angele Comic, Francoise Graindorge, Catherine Laurent, Claudine Tordjman, Sylvie Cohen, David TI Does catatonia influence the phenomenology of childhood onset schizophrenia beyond motor symptoms? SO PSYCHIATRY RESEARCH LA English DT Article DE childhood onset; schizophrenia; catatonia ID AUTISTIC SPECTRUM DISORDERS; RATING-SCALE; DEVELOPMENTAL DISORDER; CLINICAL-RELEVANCE; ADOLESCENTS; CHILDREN; FEATURES AB Childhood onset schizophrenia (COS) and catatonia (C) are rare and severe psychiatric disorders. The aim of this study was to compare the phenomenology of COS with and without catatonia. We examined 33 cases consecutively referred to two major public university hospitals in Paris. There were 18 cases of COS (age = 15.9 +/- 0.8 years) and 15 of COS+C (age = 15.4 +/- 1.4 years). Patients were referred over the course of 3 and 9 years, respectively. Psychiatric assessment included socio-demographic, clinical and psychometric variables: the Brief Psychiatric Rating Scale (BPRS), the Scales for the Assessment of Positive (SAPS) and Negative Symptoms (SANS), and a catatonia rating scale. Patients with COS + C appeared to be more severely ill at admission and discharge compared with COS in nearly all clinical scores. They also exhibited significantly longer episode duration (50.8 weeks +/- 4.8 vs 20.6 +/- 19.5). On the basis of multivariate logistic regression, the only clinical measure which significantly predicted group membership was the SANS Affective Flattening score (odds ratio = 1.24; 95% CI = 1.06-1.43). Our findings strongly suggest that catatonic COS differs from COS in ways that extend beyond motor symptoms. The SANS and SAPS scales, commonly used in schizophrenia, are not detailed enough to accurately describe catatonia in COS. The use of a catatonia rating scale is recommended to enhance recognition of and research into COS with catatonia. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 [Bonnot, Olivier; Consoli, Angele; Cohen, David] Univ Paris 06, Hop Pitie Salpetriere, AP HP, Dept Child & Adolescent Psychiat, Paris, France. [Tanguy, Marie-Laure] Univ Paris 06, Hop Pitie Salpetriere, AP HP, Dept Biostat, Paris, France. [Consoli, Angele; Comic, Francoise; Cohen, David] Univ Paris 06, CNRS, FRE Cognit & Dev 2987, Paris, France. [Graindorge, Catherine] Fdn Vallee, Fac Kremlin Bicerte, Dept Child & Adolescent Psychiat, Gentilly, France. [Laurent, Claudine] NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. [Tordjman, Sylvie] CHU Guillaume Regnier, Dept Child & Adolescent Psychiat, Rennes, France. RP Cohen, D (reprint author), Grp Hosp Pitie Salpetriere, Dept Child & Adolescent Psychiat, AP HP, 47-83 Blvd Hop, F-75013 Paris, France. EM david.cohen@psl.ap-hop-paris.fr NR 34 TC 7 Z9 7 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 15 PY 2008 VL 158 IS 3 BP 356 EP 362 DI 10.1016/j.psychres.2006.09.006 PG 7 WC Psychiatry SC Psychiatry GA 294BL UT WOS:000255379000010 PM 18272234 ER PT J AU Volkow, ND Ma, Y Zhu, W Fowler, JS Li, J Rao, M Mueller, K Pradhan, K Wong, C Wang, GJ AF Volkow, Nora D. Ma, Yerning Zhu, Wei Fowler, Joanna S. Li, Juan Rao, Manlong Mueller, Klaus Pradhan, Kith Wong, Christopher Wang, Gene-Jack TI Moderate doses of alcohol disrupt the functional organization of the human brain SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE imaging; PET; heterogeneity; addiction; coefficient of variation ID CEREBRAL BLOOD-FLOW; ETHANOL; INTOXICATION; METABOLISM; GLUCOSE; STIMULATION; ACTIVATION; CORTEX; REWARD; EEG AB Acute alcohol administration decreases overall brain glucose metabolism, which serves as a marker of brain activity. The behavioral effects of alcohol, however, are likely to reflect not only changes in regional brain activity but also the patterns of brain functional organization. Here we assessed the effects of a moderate dose of alcohol on the patterns of brain activity and cerebral differentiation. We measured brain glucose metabolism in 20 healthy controls with positron emission tomography and fluorodeoxyglucose during baseline and during alcohol intoxication (0.75 g/kg). We used the coefficient of variation (CV) to assess changes in brain metabolic homogeneity, which we used as a marker for cerebral differentiation. We found that alcohol decreased the CV in the brain and this effect was independent of the decrements in overall glucose metabolism. Our study revealed marked disruption in brain activity during alcohol intoxication including decreases in global and regional brain differentiation, a loss of right versus left brain metabolic laterality and a shift in the predominance of activity from cortical to limbic brain regions. The widespread nature of the changes induced by a moderate dose of alcohol is likely to contribute to the marked disruption of alcohol on behavior, mood, cognition and motor activity. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Zhu, Wei; Li, Juan; Rao, Manlong] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Rockville, MD 20852 USA. [Volkow, Nora D.; Ma, Yerning] NIAAA, Bethesda, MD 20892 USA. [Fowler, Joanna S.; Wong, Christopher] Assoc Univ Inc, Brookhaven Natl Lab, Med & Chem Dept, Upton, NY 11973 USA. [Mueller, Klaus; Pradhan, Kith] SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11794 USA. RP Zhu, W (reprint author), SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. EM zhu@ams.sunysb.edu FU Intramural NIH HHS [Z01 AA000550-04]; NCRR NIH HHS [3 M01 RR010710-06S1, M01 RR010710]; NIA NIH HHS [2 P30 AG08051-11, P30 AG008051]; NIAAA NIH HHS [AA09481, R01 AA009481, R01 AA009481-14]; NIDA NIH HHS [R01 DA006891, R01 DA006891-14] NR 22 TC 25 Z9 25 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 15 PY 2008 VL 162 IS 3 BP 205 EP 213 DI 10.1016/j.pscychresns.2007.04.010 PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 290KQ UT WOS:000255122100003 PM 18280711 ER PT J AU Hunsberger, S Graubard, BI Korn, EL AF Hunsberger, Sally Graubard, Barry I. Korn, Edward L. TI Testing logistic regression coefficients with clustered data and few positive outcomes SO STATISTICS IN MEDICINE LA English DT Article DE bootstrap; clustering; generalized Wald statistics; generalized score statistics; goodness of fit; survey methods ID GOODNESS-OF-FIT; CORRELATED BINARY VARIABLES; GENERALIZED LINEAR-MODELS; DISTRIBUTIONS; STATISTICS AB Applications frquently involve logistic regression analysis with clustered data where there are few positive outcomes in some of the independent variable categories. For example, an application is given here that analyzes the association of asthma with various demographic variables and risk factors using data from the third National Health and Nutrition Examination Survey, a weighted multi stage cluster sample. Although there are 742 asthma cases in all (out of (8 395 individuals), for one of the categories of one of the independent variables there are only 25 asthma cases (out of 695 individuals). Generalized Wald and score hypothesis tests, which use appropriate cluster-level variance estimators, and a bootstrap hypothesis test have been proposed for testing logistic regression coefficients with cluster samples. When there are few positive outcomes, simulations presented in this paper show that these tests can sometimes have either inflated or very conservative levels. A simulation-based method is proposed for testing logistic regression coefficients with cluster samples when there are few positive outcomes. This testing methodology is shown to compare favorably with the generalized Wald and score tests and the bootstrap hypothesis test in terms of maintaining nominal levels. The proposed method is also useful when testing goodness-of-fit of logistic regression models using deciles-of-risk tables. Published in 2007 by John Wiley & Sons, Ltd. C1 [Hunsberger, Sally; Korn, Edward L.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. [Graubard, Barry I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hunsberger, S (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA. EM sallyh@ctep.nci.nih.gov NR 33 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD APR 15 PY 2008 VL 27 IS 8 BP 1305 EP 1324 DI 10.1002/sim.3011 PG 20 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 291QA UT WOS:000255210700009 PM 17705348 ER PT J AU Olivero, OA Ming, JM Das, S Vazquez, IL Richardson, DL Weston, A Poirier, MC AF Olivero, Ofelia A. Ming, Jessica M. Das, Shreyasi Vazquez, Irma L. Richardson, Diana L. Weston, Ainsley Poirier, Miriam C. TI Human inter-individual variability in metabolism and genotoxic response to zidovudine SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE AZT; nucleoside analogs; thymidine kinase I ID HUMAN-IMMUNODEFICIENCY-VIRUS; THYMIDINE KINASE GENE; REVERSE-TRANSCRIPTASE; DRUG-RESISTANCE; PREGNANT-WOMEN; HUMAN-CELLS; AZT; 3'-AZIDO-3'-DEOXYTHYMIDINE; PHARMACOKINETICS; CARCINOGENICITY AB A mainstay of the antiretroviral drugs used for therapy of HIV- 1, zidovudine (AZT) is genotoxic and becomes incorporated into DNA. Here we explored host inter-individual variability in AZT-DNA incorporation, by AZT radioimmunoassay (RIA), using 19 different strains of normal human mammary epithelial cells (NHMECs) exposed for 24 h to 200 mu M AZT. Twelve of the 19 NEMEC strains showed detectable AZT-DNA incorporation levels (16 to 259 molecules of AZT/10(6) nucleotides), while 7 NEMEC strains did not show detectable AZT-DNA incorporation. In order to explore the basis for this variability, we compared the 2 NEMEC strains that showed the highest levels of AZT-DNA incorporation (HI and H2) with 2 strains showing no detectable AZT-DNA incorporation (L1 and L2). All 4 strains had similar (>= 80%) cell survival, low levels of accumulation of cells in S-phase, and no relevant differences in response to the direct-acting mutagen bleomycin (BLM). Finally, when levels of thymidine kinase I (TK1), the first enzyme in the pathway for incorporation of AZT into DNA, were determined by Western blot analysis in all 19 NEMEC strains at 24 h of AZT exposure, higher TK1 protein levels were found in the 12 strains showing AZT-DNA incorporation, compared to the 7 showing no incorporation (p=0.0005, Mann-Whitney test). Furthermore, strains L1 and L2, which did not show AZT-DNA incorporation at 24 h, did have measurable incorporation by 48 and 72 h. These data suggest that variability in AZT-DNA incorporation may be modulated by inter-individual differences in the rate of induction of TK1 in response to AZT exposure. Published by Elsevier Inc. C1 [Olivero, Ofelia A.; Ming, Jessica M.; Das, Shreyasi; Vazquez, Irma L.; Poirier, Miriam C.] NCI, Lab Canc Biol & Genet, Carcinogen DNA Interact Sect, NIH, Bethesda, MD 20892 USA. [Richardson, Diana L.; Weston, Ainsley] CDC, NIOSH, Toxicol & Mol Biol Branch, Morgantown, WV 26505 USA. RP Olivero, OA (reprint author), NCI, Lab Canc Biol & Genet, Carcinogen DNA Interact Sect, NIH, 37 Convent Dr MSC 4255,Bldg 37 Rm 4032B, Bethesda, MD 20892 USA. EM oliveroo@exchange.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 32 TC 5 Z9 5 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD APR 15 PY 2008 VL 228 IS 2 BP 158 EP 164 DI 10.1016/j.taap.2007.12.005 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 295SN UT WOS:000255494300004 PM 18206198 ER PT J AU Lo, YC Liu, YX Lin, YC Shih, YT Liu, CM Burka, LT AF Lo, Yi-Ching Liu, Yuxin Lin, Yi-Chin Shih, Yu-Tzu Liu, Chi-Ming Burka, Leo T. TI Neuronal effects of 4-t-Butylcatechol: A model for catechol-containing antioxidants SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE 4-t-Butyleatechol; antioxidant; neurons; microglia; oxidative stress; inflammation ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; GENE-EXPRESSION; PARKINSONS-DISEASE; INDUCED APOPTOSIS; NADPH OXIDASE; UP-REGULATION; INFLAMMATION; MICROGLIA AB Many herbal medicines and dietary supplements sold as aids to improve memory or treat neurodegenerative diseases or have other favorable effects on the CNS contain a catechol or similar 1,2-dihydroxy aromatic moiety in their structure. As an approach to isolate and examine the neuroprotective properties of catechols, a simple catechol 4-t-Butyleatechol (TBC) has been used as a model. In this study, we investigated the effects of TBC on lipopolysaccharide (LPS)-activated microglial-induced neurotoxicity by using the in vitro model of coculture murine microglial-like cell line HAPI with the neuronal-like human neuroblastoma cell line SH-SY5Y. We also examined the effects of TBC on 6-hydroxydopamine (6-OHDA)induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. TBC at concentrations from 0. 1 - 10 mu M had no toxic effect on HAPI cells and SH-SY5Y cells, and it inhibited LPS (100ng/ml)-induced increases of superoxide, intracellular ROS, gp91(Phox), NOS and a decrease of HO-1 in HAPI cells. Under coculture condition, TBC significantly reduced LPS-activated microglia-induced dopaminergic SH-SY5Y cells death. Moreover, TBC (0. 1 - 10 mu M) inhibited 6-OHDA-induced increases of intracellular ROS, NOS, nNOS, and a decrease of mitochondria membrane potential, and cell death in SH-SY5Y cells. However, the neurotoxic effects of TBC (100 mu M) on SH-SY5Y cells were also observed including the decrease in mitochondria membrane potential and the increase in COX-2 expression and cell death. TBC-induced SH-SY5Y cell death was attenuated by pretreatment with NS-398, a selective COX-2 inhibitor. In conclusion, this study suggests that TBC might possess protective effects on inflammation- and oxidative stress-related neurodegenerative disorders. However, the high concentration of TBC might be toxic, at least in part, for increasing COX-2 expression. (C) 2007 Elsevier Inc. All rights reserved. C1 [Lo, Yi-Ching; Lin, Yi-Chin; Shih, Yu-Tzu; Liu, Chi-Ming] Kaohsiung Med Univ, Coll Med, Inst Med, Dept Pharmacol, Kaohsiung 807, Taiwan. [Liu, Yuxin] NIEHS, Lab Pharmacol & Chem, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. [Burka, Leo T.] NIEHS, Lab Pharmacol & Chem, Chem Sect, Res Triangle Pk, NC 27709 USA. RP Lo, YC (reprint author), Kaohsiung Med Univ, Coll Med, Inst Med, Dept Pharmacol, 100 Shih Chuan 1st Rd, Kaohsiung 807, Taiwan. EM yichlo@kmu.edu.tw RI Lo, Yi-Ching/A-1536-2010 FU Intramural NIH HHS [Z01 ES021075-24] NR 32 TC 9 Z9 9 U1 2 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 APR 15 PY 2008 VL 228 IS 2 BP 247 EP 255 DI 10.1016/j.taap.2007.12.001 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 295SN UT WOS:000255494300012 PM 18190940 ER PT J AU Luger, D Silver, PB Tang, J Cua, D Chen, Z Iwakura, Y Bowman, EP Sgambellone, NM Chan, CC Caspi, RR AF Luger, Dror Silver, Phyllis B. Tang, Jun Cua, Daniel Chen, Zoe Iwakura, Yoichiro Bowman, Edward P. Sgambellone, Nicole M. Chan, Chi-Chao Caspi, Rachel R. TI Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RETINOID-BINDING PROTEIN; CENTRAL-NERVOUS-SYSTEM; REGULATORY T-CELLS; INTERFERON-GAMMA; HUMAN IRBP; IFN-GAMMA; MICE; IL-23; INFLAMMATION; UVEITIS AB Experimental autoimmune uveitis ( EAU) represents autoimmune uveitis in humans. We examined the role of the interleukin (IL)-23-IL-17 and IL-12-T helper cell (Th) 1 pathways in the pathogenesis of EAU. IL-23 but not IL-12 was necessary to elicit disease by immunization with the retinal antigen (Ag) interphotoreceptor retinoid-binding protein ( IRBP) in complete Freund's adjuvant. IL-17 played a dominant role in this model; its neutralization prevented or reversed disease, and Th17 effector cells induced EAU in the absence of interferon (IFN)-gamma. In a transfer model, however, a polarized Th1 line could induce severe EAU independently of host IL-17. Furthermore, induction of EAU with IRBP-pulsed mature dendritic cells required generation of an IFN-gamma-producing effector response, and an IL-17 response by itself was insufficient to elicit pathology. Finally, genetic deficiency of IL-17 did not abrogate EAU susceptibility. Thus, autoimmune pathology can develop in the context of either a Th17 or a Th1 effector response depending on the model. The data suggest that the dominant effector phenotype may be determined at least in part by conditions present during initial exposure to Ag, including the quality/quantity of Toll-like receptor stimulation and/or type of Ag-presenting cells. These data also raise the possibility that the nonredundant requirement for IL-23 in EAU may extend beyond its role in promoting the Th17 effector response and help provide a balance in the current Th1 versus Th17 paradigm. C1 [Luger, Dror; Silver, Phyllis B.; Tang, Jun; Chan, Chi-Chao; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Cua, Daniel; Chen, Zoe; Bowman, Edward P.; Sgambellone, Nicole M.] DNAX Res Inst Mol & Cellular Biol Inc, Schering Plough SpA, Palo Alto, CA 94304 USA. [Iwakura, Yoichiro] Univ Tokyo, Tokyo 1088639, Japan. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov RI Iwakura, Yoichiro/E-5457-2011; OI Iwakura, Yoichiro/0000-0002-9934-5775; Caspi, Rachel/0000-0002-7140-7671 FU Intramural NIH HHS [Z01 EY000184-25, Z99 EY999999] NR 54 TC 395 Z9 425 U1 0 U2 13 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 14 PY 2008 VL 205 IS 4 BP 799 EP 810 DI 10.1084/jem.20071258 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 292DC UT WOS:000255245700008 PM 18391061 ER PT J AU Tenbusch, M Kuate, S Tippler, B Gerlach, N Schimmer, S Dittmer, U Uberla, K AF Tenbusch, Matthias Kuate, Seraphin Tippler, Bettina Gerlach, Nicole Schimmer, Simone Dittmer, Ulf Ueberla, Klaus TI Coexpression of GM-CSF and antigen in DNA prime-adenoviral vector boost immunization enhances polyfunctional CD8+ T cell responses, whereas expression of GM-CSF antigen fusion protein induces autoimmunity SO BMC IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; PULMONARY ALVEOLAR PROTEINOSIS; FRIEND RETROVIRUS INFECTION; IMMUNE-RESPONSES; DENDRITIC CELLS; RECOMBINANT ADENOVIRUSES; VACCINE; INDUCTION; HIV-1; IMMUNOGENICITY AB Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown promising results as a cytokine adjuvant for antiviral vaccines and in various models of tumor gene therapy. To explore whether the targeting of antigens to GM-CSF receptors on antigen-presenting cells enhances antigen-specific CD8 T-cell responses, fusion proteins of GM-CSF and ovalbumin (OVA) were expressed by DNA and adenoviral vector vaccines. In addition, bicistronic vectors allowing independent expression of the antigen and the cytokine were tested in parallel. Results: In vitro, the GM-CSF ovalbumin fusion protein (GM-OVA) led to the better stimulation of OVA-specific CD8+ T cells by antigen-presenting cells than OVA and GM-CSF given as two separate proteins. However, prime-boost immunizations of mice with DNA and adenoviral vector vaccines encoding GM-OVA suppressed CD8+ T-cell responses to OVA. OVA-specific IgG2a antibody levels were also reduced, while the IgG1 antibody response was enhanced. Suppression of CD8+ T cell responses by GM-OVA vaccines was associated with the induction of neutralizing antibodies to GM-CSF. In contrast, the coexpression of GM-CSF and antigens in DNA prime adenoviral boost immunizations led to a striking expansion of polyfunctional OVA-specific CD8+ T cells without the induction of autoantibodies. Conclusion: The induction of autoantibodies suggests a general note of caution regarding the use of highly immunogenic viral vector vaccines encoding fusion proteins between antigens and host proteins. In contrast, the expansion of polyfunctional OVA-specific CD8+ T cells after immunizations with bicistronic vectors further support a potential application of GM-CSF as an adjuvant for heterologous prime-boost regimens with genetic vaccines. Since DNA prime adenoviral vector boost regimenes are presently considered as one of the most efficient ways to induce CD8+ T cell responses in mice, non-human primates and humans, further enhancement of this response by GM-CSF is a striking observation. C1 [Tenbusch, Matthias; Kuate, Seraphin; Tippler, Bettina; Ueberla, Klaus] Ruhr Univ Bochum, Dept Mol & Med Virol, D-44801 Bochum, Germany. [Gerlach, Nicole; Schimmer, Simone; Dittmer, Ulf] Univ Duisburg Gesamthsch, Inst Virol, D-45122 Essen, Germany. [Kuate, Seraphin] NCI, Immune Biol Retroviral Infect, VB,CCR, NIH, Bethesda, MD USA. RP Uberla, K (reprint author), Ruhr Univ Bochum, Dept Mol & Med Virol, D-44801 Bochum, Germany. EM matthias.tenbusch@rub.de; kuates@mail.nih.gov; bettina.g.tippler@ruhr-uni-bochum.de; nicole.gerlach@uni-duisburg-essen.de; simone.schimmer@uni-duisburg-essen.de; ulf.dittmer@uni-due.de; klaus.ueberla@ruhr-uni-bochum.de RI Uberla, Klaus/C-5676-2008 NR 60 TC 19 Z9 19 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD APR 11 PY 2008 VL 9 AR 13 DI 10.1186/1471-2172-9-13 PG 15 WC Immunology SC Immunology GA 297ZY UT WOS:000255657100001 PM 18405363 ER PT J AU Terracciano, A Lockenhoff, CE Crum, RM Bienvenu, OJ Costa, PT AF Terracciano, Antonio Loeckenhoff, Corinna E. Crum, Rosa M. Bienvenu, O. Joseph Costa, Paul T., Jr. TI Five-factor model personality profiles of drug users SO BMC PSYCHIATRY LA English DT Article ID FOLLOW-UP; PSYCHIATRIC-DISORDERS; CIGARETTE-SMOKING; OPIOID DEPENDENCE; MAJOR DEPRESSION; TOBACCO USE; TRAITS; NICOTINE; METAANALYSIS; PREVALENCE AB Background: Personality traits are considered risk factors for drug use, and, in turn, the psychoactive substances impact individuals' traits. Furthermore, there is increasing interest in developing treatment approaches that match an individual's personality profile. To advance our knowledge of the role of individual differences in drug use, the present study compares the personality profile of tobacco, marijuana, cocaine, and heroin users and non-users using the wide spectrum Five-Factor Model (FFM) of personality in a diverse community sample. Method: Participants (N = 1,102; mean age = 57) were part of the Epidemiologic Catchment Area (ECA) program in Baltimore, MD, USA. The sample was drawn from a community with a wide range of socio-economic conditions. Personality traits were assessed with the Revised NEO Personality Inventory (NEO-PI-R), and psychoactive substance use was assessed with systematic interview. Results: Compared to never smokers, current cigarette smokers score lower on Conscientiousness and higher on Neuroticism. Similar, but more extreme, is the profile of cocaine/heroin users, which score very high on Neuroticism, especially Vulnerability, and very low on Conscientiousness, particularly Competence, Achievement-Striving, and Deliberation. By contrast, marijuana users score high on Openness to Experience, average on Neuroticism, but low on Agreeableness and Conscientiousness. Conclusion: In addition to confirming high levels of negative affect and impulsive traits, this study highlights the links between drug use and low Conscientiousness. These links provide insight into the etiology of drug use and have implications for public health interventions. C1 [Terracciano, Antonio; Loeckenhoff, Corinna E.; Costa, Paul T., Jr.] NIA, NIH, DHHS, Baltimore, MD 21224 USA. [Crum, Rosa M.; Bienvenu, O. Joseph; Costa, Paul T., Jr.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Terracciano, A (reprint author), NIA, NIH, DHHS, Baltimore, MD 21224 USA. EM TerraccianoA@grc.nia.nih.gov; loeckenhoffc@grc.nia.nih.gov; rcrum@jhsph.edu; jbienven@mail.jhmi.edu; costap@grc.nia.nih.gov RI terracciano, antonio/B-1884-2008; OI Loeckenhoff, Corinna/0000-0003-1605-1323; Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS [ZIA AG000197-03, Z99 AG999999, ZIA AG000197-04]; NIMH NIH HHS [K23 MH064543, K23-MH64543, MH47447, MH50616, R01 MH047447, R01 MH050616] NR 62 TC 97 Z9 99 U1 4 U2 33 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD APR 11 PY 2008 VL 8 AR 22 DI 10.1186/1471-244X-8-22 PG 10 WC Psychiatry SC Psychiatry GA 296RC UT WOS:000255562500001 PM 18405382 ER PT J AU Vinogradova, TM Sirenko, S Lyashkov, AE Younes, A Li, Y Zhu, WZ Yang, DM Ruknudin, AM Spurgeon, H Lakatta, EG AF Vinogradova, Tatiana M. Sirenko, Syevda Lyashkov, Alexey E. Younes, Antoine Li, Yue Zhu, Weizhong Yang, Dongmei Ruknudin, Abdul M. Spurgeon, Harold Lakatta, Edward G. TI Constitutive phosphodiesterase activity restricts spontaneous beating rate of cardiac pacemaker cells by suppressing local Ca2+ releases SO CIRCULATION RESEARCH LA English DT Article DE sinoatrial node; phosphodiesterase; ryanodine receptors; local Ca2+ release ID SINOATRIAL NODAL CELLS; DIASTOLIC DEPOLARIZATION; RYANODINE RECEPTOR; CYCLIC-AMP; STIMULATION; INHIBITORS; AUTOMATICITY; MILRINONE; CALCIUM; SYSTEM AB Spontaneous beating of rabbit sinoatrial node cells (SANCs) is controlled by cAMP-mediated, protein kinase A-dependent local subsarcolemmal ryanodine receptor Ca2+ releases (LCRs). LCRs activated an inward Na+/Ca2+ exchange current that increases the terminal diastolic depolarization rate and, therefore, the spontaneous SANC beating rate. Basal cAMP in SANCs is elevated, suggesting that cAMP degradation by phosphodiesterases (PDEs) may be low. Surprisingly, total suppression of PDE activity with a broad-spectrum PDE inhibitor, 3'-isobutylmethylxanthine (IBMX), produced a 9-fold increase in the cAMP level, doubled cAMP-mediated, protein kinase A-dependent phospholamban phosphorylation, and increased SANC firing rate by approximate to 55%, indicating a high basal activity of PDEs in SANCs. A comparison of specific PDE1 to -5 inhibitors revealed that the specific PDE3 inhibitor, milrinone, accelerated spontaneous firing by approximate to 47% (effects of others were minor) and increased amplitude of L-type Ca2+ current (I-Ca,I-L) by approximate to 46%, indicating that PDE3 was the major constitutively active PDE in the basal state. PDE-dependent control of the spontaneous SANC firing was critically dependent on subsarcolemmal LCRs, ie, PDE inhibition increased LCR amplitude and size and decreased LCR period, leading to earlier and augmented LCR Ca2+ release, Na+/Ca2+ exchange current, and an increase in the firing rate. When ryanodine receptors were disabled by ryanodine, neither IBMX nor milrinone was able to amplify LCRs, accelerate diastolic depolarization rate, or increase the SANC firing rate, despite preserved PDE inhibition-induced augmentation of I-Ca,I-L amplitude. Thus, basal constitutive PDE activation provides a novel and powerful mechanism to decrease cAMP, limit cAMP-mediated, protein kinase A-dependent increase of diastolic ryanodine receptor Ca2+ release, and restrict the spontaneous SANC beating rate. C1 [Vinogradova, Tatiana M.; Sirenko, Syevda; Lyashkov, Alexey E.; Younes, Antoine; Li, Yue; Zhu, Weizhong; Yang, Dongmei; Ruknudin, Abdul M.; Spurgeon, Harold; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Vinogradova, TM (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vinogradovat@grc.nia.nih.gov FU Intramural NIH HHS NR 26 TC 58 Z9 59 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD APR 11 PY 2008 VL 102 IS 7 BP 761 EP 769 DI 10.1161/CIRCRESAHA.107.161679 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 287JV UT WOS:000254914300005 PM 18276917 ER PT J AU Keszler, A Piknova, B Schechter, AN Hogg, N AF Keszler, Agnes Piknova, Barbora Schechter, Alan N. Hogg, Neil TI The reaction between nitrite and oxyhemoglobin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYDROGEN-PEROXIDE; MEDIATED OXIDATION; INDUCED METHEMOGLOBINEMIA; AUTOCATALYTIC OXIDATION; NITROGEN-DIOXIDE; HUMAN-HEMOGLOBIN; OXIDE; MYOGLOBIN; MECHANISM; DEOXYHEMOGLOBIN AB The nitrite anion (NO(2)(-)) has recently received much attention as an endogenous nitric oxide source that has the potential to be supplemented for therapeutic benefit. One major mechanism of nitrite reduction is the direct reaction between this anion and the ferrous heme group of deoxygenated hemoglobin. However, the reaction of nitrite with oxyhemoglobin (oxyHb) is well established and generates nitrate and methemoglobin (metHb). Several mechanisms have been proposed that involve the intermediacy of protein-free radicals, ferryl heme, nitrogen dioxide (NO(2)), and hydrogen peroxide (H(2)O(2)) in an autocatalytic free radical chain reaction, which could potentially limit the usefulness of nitrite therapy. In this study we show that none of the previously published mechanisms is sufficient to fully explain the kinetics of the reaction of nitrite with oxyHb. Based on experimental data and kinetic simulation, we have modified previous models for this reaction mechanism and show that the new model proposed here is consistent with experimental data. The important feature of this model is that, whereas previously both H(2)O(2) and NO(2) were thought to be integral to both the initiation and propagation steps, H(2)O(2) now only plays a role as an initiator species, and NO(2) only plays a role as an autocatalytic propagatory species. The consequences of uncoupling the roles of H(2)O(2) and NO(2) in the reaction mechanism for the in vivo reactivity of nitrite are discussed. C1 [Keszler, Agnes; Hogg, Neil] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. [Keszler, Agnes; Hogg, Neil] Med Coll Wisconsin, Free Radical Res Ctr, Milwaukee, WI 53226 USA. [Piknova, Barbora; Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Hogg, N (reprint author), 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM nhogg@mcw.edu FU NIBIB NIH HHS [EB 001980]; NIGMS NIH HHS [GM 55792] NR 40 TC 48 Z9 48 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 APR 11 PY 2008 VL 283 IS 15 BP 9615 EP 9622 DI 10.1074/jbc.M705630200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 283YE UT WOS:000254671600015 PM 18203719 ER PT J AU Ito, Y Goto, T Yamada, S Ohno, T Matsumoto, H Oka, H Ito, Y AF Ito, Yuko Goto, Tomomi Yamada, SadaJi Ohno, Tsutomu Matsumoto, Hiroshi Oka, Hisao Ito, Yoichiro TI Rapid determination of carbamate pesticides in food using dual counter-current chromatography directly interfaced with mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE dual counter-current chromatography-tandem mass spectrometry; carbaryl; fenobucarb; methomyl; vegetable oil; orange; spinach ID N-METHYLCARBAMATE PESTICIDES; CHEMICAL-IONIZATION; NATURAL-PRODUCTS AB Dual counter-current chromatography (dual CCC)-tandem mass spectrometry (MS/MS) was successfully performed with a newly designed spiral column for dual CCC. The small column capacity required for directly coupling with electrospray MS/MS was accomplished by forming a rectangular spiral groove on a plastic disk and sealing it with a PTFE sheet. This novel dual CCC-MS/MS technique was successfully applied for the rapid determination of methomyl, fenobucarb and carbaryl pesticides in food. A two-phase solvent system of n-hexane-acetonitrile-0.1% formic acid (45:45: 10) was suitable for both good dual CCC separation and sufficient ionization of pesticides. Recoveries of these three pesticides from mandarin orange and spinach samples fortified at 0.05 mg/kg were in the range of 93-107% with relative standard deviations of 2.4-3.8%. (c) 2008 Elsevier B.V. All rights reserved. C1 [Ito, Yuko; Goto, Tomomi; Yamada, SadaJi; Ohno, Tsutomu; Matsumoto, Hiroshi] Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 4628576, Japan. [Oka, Hisao] Kinjo Gakuin Univ, Moriyama Ku, Nagoya, Aichi 4638521, Japan. [Ito, Yoichiro] NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 4628576, Japan. EM yuuko_1_itou@pref.aichi.1g.jp; yuuko_1_itou@pref.aichi.1g.jp NR 16 TC 18 Z9 19 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 11 PY 2008 VL 1187 IS 1-2 BP 53 EP 57 DI 10.1016/j.chroma.2008.01.078 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 290EE UT WOS:000255105300008 PM 18295222 ER PT J AU Brister, JR AF Brister, J. Rodney TI Origin activation requires both replicative and accessory helicases during T4 infection SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DNA; replication; origins; helicase; T4 ID STRANDED-DNA-BINDING; BACTERIOPHAGE-T4 INFECTION; GENE-EXPRESSION; DDA HELICASE; PROTEIN; RECOMBINATION; MUTANT; STIMULATION; MECHANISMS; INITIATION AB The bacteriophage T4 has served as an in vitro model for the study of DNA replication for several decades, yet less is known about this process during infection. Recent work has shown that viral DNA synthesis is initiated from at least five origins of replication distributed across the 172 kb chromosome, but continued synthesis is dependent on recombination. Two proteins are predicted to facilitate loading of the hexameric 41 helicase at the origins, the Dda accessory helicase and the 59 loading protein. Using a real time, genome-wide assay to monitor replication during infections, it is shown here that dda mutant viruses no longer preferentially initiate synthesis near the origins, implying that the Dda accessory helicase has a fundamental role in origin selection and activation. In contrast, at least two origins function efficiently without the 59 loading protein, indicating that other factors load the 41 helicase at these loci. Hence, normal T4 replication includes two mechanistically distinct classes of origins, one requiring the 59 helicase loader, and a second that does not. Since both mechanisms require an additional factor, repEB, for sustained activation, normal T4 origin function appears to include at least three common elements, origin selection and initial activation, replisome loading, and persistence. (C) 2008 Elsevier Ltd. All rights reserved. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Brister, JR (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM jamesbr@niddk.nih.gov FU Intramural NIH HHS [Z99 LM999999] NR 34 TC 5 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 11 PY 2008 VL 377 IS 5 BP 1304 EP 1313 DI 10.1016/j.jmb.2008.02.002 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 288IK UT WOS:000254979500002 PM 18314134 ER PT J AU Chin, MPS Lee, SK Chen, JB Nikolaitchik, OA Powell, DA Fivash, MJ Hu, WS AF Chin, Mario P. S. Lee, Sook-Kyung Chen, Jianbo Nikolaitchik, Olga A. Powell, Douglas A. Fivash, Mathew J., Jr. Hu, Wei-Shau TI Long-range recombination gradient between HIV-1 subtypes B and C variants caused by sequence differences in the dimerization initiation signal region SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV-1; subtype; recombination; dimerization initiation signal; RNA secondary structure ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; RETROVIRAL RECOMBINATION; GENETIC-RECOMBINATION; STRAND TRANSFER; REVERSE-TRANSCRIPTASE; GENOMIC RNA; IN-VITRO; INTERSUBTYPE RECOMBINATION; PROMOTES RECOMBINATION AB HIV-1 intersubtype recombinants have an increasingly important role in shaping the AIDS pandemic. We sought to understand the molecular mechanisms that generate intersubtype HIV-1 recombinants. We analyzed recombinants of HIV-1 subtypes B and C, and identified their crossover junctions in the viral genome from the 5' long terminal repeat (LTR) to the end of pol. We identified 56 recombination events in 56 proviruses; the distribution of these events indicated an apparent recombination gradient: there were significantly more crossover junctions in the 3' half than in the 5' half of the region analyzed. HIV-1 subtypes B and C have different dimerization initiation signal (DIS). We hypothesized that the inability of subtype B and C RNAs to form perfect base-pairing of the DIS affects the dimeric RNA structure and causes a decrease in recombination events at the 5' end of the viral genome. To test this hypothesis, we examined recombinants generated from a subtype C virus and a modified subtype B virus containing a subtype C DIS. In the 56 proviruses analyzed, we identified 96 recombination events, which are significantly more frequent than in the B/C recombinants. Furthermore, these crossover junctions were distributed evenly throughout the region analyzed, indicating that the recombination gradient was corrected by matching the DIS. Therefore, base-pairing at the DIS has an important function during HIV-1 reverse transcription, most likely in maintaining nucleic-acid structure in the complex. These findings reveal elements important to retroviral recombination and provide insights into the generation of HIV-1 intersubtype recombinants that are important to the AIDS epidemic. Published by Elsevier Ltd. C1 [Chin, Mario P. S.; Lee, Sook-Kyung; Chen, Jianbo; Nikolaitchik, Olga A.; Hu, Wei-Shau] NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. [Powell, Douglas A.; Fivash, Mathew J., Jr.] NCI, Data Management Serv Inc, Ft Detrick, MD 21702 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. EM whu@ncifcrf.gov RI Chen, Jianbo/N-3737-2014 OI Chen, Jianbo/0000-0001-6491-6577 FU Intramural NIH HHS [Z01 BC010814-01, Z01 BC010504-05] NR 52 TC 16 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 11 PY 2008 VL 377 IS 5 BP 1324 EP 1333 DI 10.1016/j.jmb.2008.02.003 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 288IK UT WOS:000254979500004 PM 18314135 ER PT J AU Leem, YE Ripmaster, TL Kelly, FD Ebina, H Heincelman, ME Zhang, K Grewal, SIS Hoffman, CS Levin, HL AF Leem, Young-Eun Ripmaster, Tracy L. Kelly, Felice D. Ebina, Hirotaka Heincelman, Marc E. Zhang, Ke Grewal, Shiv I. S. Hoffman, Charles S. Levin, Henry L. TI Retrotransposon Tf1 is targeted to pol II promoters by transcription activators SO MOLECULAR CELL LA English DT Article ID TRANSFER-RNA GENES; PROTEIN-KINASE-A; FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; CHROMATIN STRUCTURE; HIV-1 INTEGRASE; MESSENGER-RNA; LEDGF/P75; TY1; PHOSPHORYLATION AB The LTR-retrotransposon Tf1 preserves the coding capacity of its host Schizosaccharomyces pombe by integrating upstream of open reading frames (ORFs). To determine which features of the target sites were recognized by the transposon, we introduced plasmids containing candidate insertion sites into S. pombe and mapped the positions of integration. We found that Tf1 was targeted specifically to the promoters of Pol II-transcribed genes. A detailed analysis of integration in plasmids that contained either ade6 or fbp 1 revealed insertions occurred in the promoters at positions where transcription factors bound. Further experiments revealed that the activator AM p and its binding site were required for directing integration to the promoter of fbp 1. An interaction between Tf1 integrase and AM p was observed, indicating that integration at fbp1 was mediated by the activator bound to its promoter. Surprisingly, we found Tf1 contained sequences that activated transcription, and these substituted for elements of the ade6 promoter disrupted by integration. C1 [Leem, Young-Eun; Ripmaster, Tracy L.; Kelly, Felice D.; Ebina, Hirotaka; Heincelman, Marc E.; Levin, Henry L.] Eunice Kennedy Shriver NICHHD, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. [Zhang, Ke; Grewal, Shiv I. S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Hoffman, Charles S.] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. RP Levin, HL (reprint author), Eunice Kennedy Shriver NICHHD, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. EM henry_levin@nih.gov OI Hoffman, Charles/0000-0001-8700-1863 FU Intramural NIH HHS [Z01 HD001009-15, Z99 HD999999]; NIGMS NIH HHS [R01 GM046226-13S1, R01 GM046226, R01 GM046226-09, R01 GM046226-10A1, R01 GM046226-11, R01 GM046226-12, R01 GM046226-13] NR 28 TC 39 Z9 39 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 APR 11 PY 2008 VL 30 IS 1 BP 98 EP 107 DI 10.1016/j.molcel.2008.02.016 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 287TN UT WOS:000254939500012 PM 18406330 ER PT J AU Mittal, J Truskett, TM Errington, JR Hummer, G AF Mittal, Jeetain Truskett, Thomas M. Errington, Jeffrey R. Hummer, Gerhard TI Layering and position-dependent diffusive dynamics of confined fluids SO PHYSICAL REVIEW LETTERS LA English DT Article ID MOLECULAR-DYNAMICS; BAYESIAN-ANALYSIS; HARD-SPHERES; TRANSITION; LIQUID; COEFFICIENTS; SIMULATIONS; NARROW; WALLS AB We study the diffusive dynamics of a hard-sphere fluid confined between parallel smooth hard walls. The position-dependent diffusion coefficient normal to the walls is larger in regions of high local packing density. High density regions also have the largest available volume, consistent with the fast local diffusivity. Indeed, local and global diffusivities as a function of the Widom insertion probability approximately collapse onto a master curve. Parallel and average normal diffusivities are strongly coupled at high densities and deviate from bulk fluid behavior. C1 [Mittal, Jeetain; Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Truskett, Thomas M.] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. [Truskett, Thomas M.] Univ Texas Austin, Inst Theoret Chem, Austin, TX 78712 USA. [Errington, Jeffrey R.] SUNY Buffalo, Dept Chem & Biol Engn, Buffalo, NY 14260 USA. RP Mittal, J (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM jeetain@helix.nih.gov; truskett@che.utexas.edu; jerring@buffalo.edu; hummer@helix.nih.gov RI Truskett, Thomas/D-4624-2009; Errington, Jeffrey/E-8644-2011; Hummer, Gerhard/A-2546-2013; Truskett, Thomas/C-4996-2014 OI Truskett, Thomas/0000-0002-6607-6468; Errington, Jeffrey/0000-0003-0365-0271; Hummer, Gerhard/0000-0001-7768-746X; FU Intramural NIH HHS NR 23 TC 102 Z9 102 U1 2 U2 30 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 APR 11 PY 2008 VL 100 IS 14 AR 145901 DI 10.1103/PhysRevLett.100.145901 PG 4 WC Physics, Multidisciplinary SC Physics GA 287UB UT WOS:000254940900044 PM 18518049 ER PT J AU Jakupciak, JP Maggrah, A Maragh, S Maki, J Reguly, B Maki, K Wittock, R Robinson, K Wagner, PD Thayer, RE Gehman, K Gehman, T Srivastava, S Ngom, A Dakubo, GD Parr, RL AF Jakupciak, John P. Maggrah, Andrea Maragh, Samantha Maki, Jennifer Reguly, Brian Maki, Katrina Wittock, Roy Robinson, Kerry Wagner, Paul D. Thayer, Robert E. Gehman, Ken Gehman, Teresa Srivastava, Sudhir Ngom, Alioune Dakubo, Gabriel D. Parr, Ryan L. TI Facile whole mitochondrial genome resequencing from nipple aspirate fluid using MitoChip v2.0 SO BMC CANCER LA English DT Article ID BREAST-CANCER RISK; DNA MUTATIONS; DUCTAL LAVAGE; ABNORMAL-CYTOLOGY; WOMEN; IDENTIFICATION; BIOMARKERS; SPECIMENS; NUCLEAR; ATYPIA AB Background: Mutations in the mitochondrial genome (mtgenome) have been associated with many disorders, including breast cancer. Nipple aspirate fluid (NAF) from symptomatic women could potentially serve as a minimally invasive sample for breast cancer screening by detecting somatic mutations in this biofluid. This study is aimed at 1) demonstrating the feasibility of NAF recovery from symptomatic women, 2) examining the feasibility of sequencing the entire mitochondrial genome from NAF samples, 3) cross validation of the Human mitochondrial resequencing array 2.0 (MCv2), and 4) assessing the somatic mtDNA mutation rate in benign breast diseases as a potential tool for monitoring early somatic mutations associated with breast cancer. Methods: NAF and blood were obtained from women with symptomatic benign breast conditions, and we successfully assessed the mutation load in the entire mitochondrial genome of 19 of these women. DNA extracts from NAF were sequenced using the mitochondrial resequencing array MCv2 and by capillary electrophoresis (CE) methods as a quality comparison. Sequencing was performed independently at two institutions and the results compared. The germline mtDNA sequence determined using DNA isolated from the patient's blood (control) was compared to the mutations present in cellular mtDNA recovered from patient's NAF. Results: From the cohort of 28 women recruited for this study, NAF was successfully recovered from 23 participants (82%). Twenty two (96%) of the women produced fluids from both breasts. Twenty NAF samples and corresponding blood were chosen for this study. Except for one NAF sample, the whole mtgenome was successfully amplified using a single primer pair, or three pairs of overlapping primers. Comparison of MCv2 data from the two institutions demonstrates 99.200% concordance. Moreover, MCv2 data was 99.999% identical to CE sequencing, indicating that MCv2 is a reliable method to rapidly sequence the entire mtgenome. Four NAF samples contained somatic mutations. Conclusion: We have demonstrated that NAF is a suitable material for mtDNA sequence analysis using the rapid and reliable MCv2. Somatic mtDNA mutations present in NAF of women with benign breast diseases could potentially be used as risk factors for progression to breast cancer, but this will require a much larger study with clinical follow up. C1 [Maggrah, Andrea; Maki, Jennifer; Reguly, Brian; Maki, Katrina; Wittock, Roy; Robinson, Kerry; Thayer, Robert E.; Dakubo, Gabriel D.; Parr, Ryan L.] Genesis Genom Inc, Thunder Bay, ON, Canada. [Maragh, Samantha] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. [Wagner, Paul D.; Srivastava, Sudhir] NCI, Canc Prevent Div, Rockville, MD USA. [Gehman, Ken; Gehman, Teresa] Thunder Bay Reg Hlth Sci Ctr, Thunder Bay, ON, Canada. [Ngom, Alioune] Univ Windsor, Sch Comp Sci, Windsor, ON N9B 3P4, Canada. RP Parr, RL (reprint author), Genesis Genom Inc, Thunder Bay, ON, Canada. EM johnjakupciak@verizon.net; andrea.maggrah@genesisgenomics.com; samantha.maragh@nist.gov; jennifer.maki@genesisgenomics.com; brian.reguly@genesisgenomics.com; katrina.maki@genesisgenomics.com; roy.wittock@genesisgenomics.com; kerry.robinson@genesisgenomics.com; wagnerp@mail.nih.gov; robert.thayer@genesisgenomics.com; gehman@tbaytel.net; gehman@tbaytel.net; srivasts@mail.nih.gov; alioune.ngom@gmail.com; gabriel.dakubo@genesisgenomics.com; ryan.parr@genesisgenomics.com NR 33 TC 18 Z9 18 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD APR 10 PY 2008 VL 8 AR 95 DI 10.1186/1471-2407-8-95 PG 8 WC Oncology SC Oncology GA 302AH UT WOS:000255937700003 PM 18402686 ER PT J AU Savage, SA Gerstenblith, MR Goldstein, AM Mirabello, L Fargnoli, MC Peris, K Landi, MT AF Savage, Sharon A. Gerstenblith, Meg R. Goldstein, Alisa M. Mirabello, Lisa Fargnoli, Maria Concetta Peris, Ketty Landi, Maria Teresa TI Nucleotide diversity and population differentiation of the melanocortin 1 Receptor gene, MC1R SO BMC GENETICS LA English DT Article ID SKIN PIGMENTATION; CUTANEOUS MELANOMA; DNA POLYMORPHISM; RED HAIR; POSITIVE SELECTION; SEQUENCE VARIATION; CDKN2A MUTATIONS; VARIANT ALLELES; RISK; HUMANS AB Background: The melanocortin 1 receptor gene (MC1R) is responsible for normal pigment variation in humans and is highly polymorphic with numerous population-specific alleles. Some MC1R variants have been associated with skin cancer risk. Results: Allele frequency data were compiled on 55 single nucleotide polymorphisms from seven geographically distinct human populations (n = 2306 individuals). MC1R nucleotide diversity, p, was much higher (10.1 x 10(-4)) than in other genes for all subjects. A large degree of population differentiation, determined by FST, was also present, particularly between Asia and all other populations, due to the p. R163Q (c. 488 G>A) polymorphism. The least amount of differentiation was between the United States, Northern Europe, and Southern Europe. Tajima's D statistic suggested the presence of positive selection in individuals from Europe. Conclusion: This study further quantifies the degree of population-specific genetic variation and suggests that positive selection may be present in European populations in MC1R. C1 [Savage, Sharon A.; Mirabello, Lisa] NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,Clin Genet Branch, Bethesda, MD 20892 USA. [Gerstenblith, Meg R.; Goldstein, Alisa M.; Landi, Maria Teresa] NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,Genet Epidemiol Branch, Bethesda, MD 20892 USA. [Fargnoli, Maria Concetta; Peris, Ketty] Univ Aquila, Dept Dermatol, I-67100 Laquila, Italy. RP Savage, SA (reprint author), NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,Clin Genet Branch, Bethesda, MD 20892 USA. EM savagesh@mail.nih.gov; mgerstenblith@gmail.com; goldstea@mail.nih.gov; mirabellol@mail.nih.gov; fargnoli@univaq.it; peris@univaq.it; andim@mail.nih.gov RI Savage, Sharon/B-9747-2015; OI Savage, Sharon/0000-0001-6006-0740; Peris, Ketty/0000-0002-5237-0463; Fargnoli, Maria Concetta/0000-0002-7249-2556 FU Intramural NIH HHS NR 56 TC 16 Z9 17 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD APR 10 PY 2008 VL 9 AR 31 DI 10.1186/1471-2156-9-31 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 298TT UT WOS:000255710700003 PM 18402696 ER PT J AU Strasak, AM Kelleher, CC Brant, LJ Rapp, K Ruttmann, E Concin, H Diem, G Pfeiffer, KP Ulmer, H AF Strasak, Alexander M. Kelleher, Cecily C. Brant, Larry J. Rapp, Kilian Ruttmann, Elfriede Concin, Hans Diem, Guenter Pfeiffer, Karl P. Ulmer, Hanno CA VHM&PP Study Grp TI Serum uric acid is an independent predictor for all major forms of cardiovascular death in 28,613 elderly women: A prospective 21-year follow-up study SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE cardiovascular mortality; serum uric acid; risk factors; elderly women; epidemiology ID CORONARY-HEART-DISEASE; ALL-CAUSE MORTALITY; RISK-FACTORS; MYOCARDIAL-INFARCTION; SEX-DIFFERENCES; BLOOD-PRESSURE; STROKE; HYPERURICEMIA; COHORT; MEN AB Background: The role of serum uric acid (SUA) as a risk factor for cardiovascular disease (CVD) remains controversial. Little is known about its predictive value for mortality from congestive heart failure (CHF) and stroke, particularly in elderly, post-menopausal women. Methods: The relation of SUA to risk of death from total CVD, CHF, stroke and coronary heart disease (CHD) was examined prospectively in a large cohort of 28613 elderly Austrian women (mean age 62.3 years), followed-up for a median of 15.2 years. Adjusted Cox proportional hazards models were calculated to evaluate SUA as an independent predictor for fatal CVD events. Results: SUA in the highest quartile (>= 5.41 mg/dL) was significantly associated with mortality from total CVD (p<0.0001), showing a clear dose-response relationship; the adjusted hazard ratio (95% CI) in comparison to the lowest SUA quartile was 1.35 (1.20-1.52). In subgroup analyses SUA was independently predictive for deaths from acute and subacute (p<0.0001) and chronic forms (p = 0.035) of CHD, yielding adjusted hazard ratios for the highest versus lowest SUA quartile of 1.58 (1.19-2.10) and 1.25 (1.01-1.56), respectively. SUA was further significantly related to fatal CHF (p<0.0001) and stroke (p = 0.018); the adjusted hazard ratios for the highest versus lowest SUA quartile were 1.50 (1.04-2.17) and 1.37 (1.09-1.74), respectively. Conclusions: These findings, for the first time, demonstrate that SUA is an independent predictor for all major forms of death from CVD including acute, subacute and chronic forms of CHD, CHF and stroke in elderly, post-menopausal women. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Strasak, Alexander M.; Pfeiffer, Karl P.; Ulmer, Hanno] Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, A-6020 Innsbruck, Austria. [Kelleher, Cecily C.] Univ Coll Dublin, Sch Publ Hlth & Populat Sci, Dublin, Ireland. [Brant, Larry J.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Rapp, Kilian] Univ Ulm, Dept Epidemiol, D-89069 Ulm, Germany. [Ruttmann, Elfriede] Innsbruck Med Univ, Dept Cardiac Surg, A-6020 Innsbruck, Austria. [Concin, Hans; Diem, Guenter; Ulmer, Hanno] Agcy Prevent & Social Med, Bregenz, Austria. RP Strasak, AM (reprint author), Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Schoepfstr 41, A-6020 Innsbruck, Austria. EM alexander.strasak@i-med.ac.at RI Ruttmann, Elfriede/D-6501-2011; vhmpp, aks/F-9756-2012; Klenk, Jochen/C-2164-2012; Ulmer, Hanno/C-3488-2011; OI Ulmer, Hanno/0000-0001-5911-1002; Klenk, Jochen/0000-0002-5987-447X NR 44 TC 105 Z9 119 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD APR 10 PY 2008 VL 125 IS 2 BP 232 EP 239 DI 10.1016/j.ijcard.2007.11.094 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 302SS UT WOS:000255990200015 PM 18237790 ER PT J AU Ivanov, AA Wang, B Klutz, AM Chen, VL Gao, ZG Jacobsom, KA AF Ivanov, Andrei A. Wang, Ben Klutz, Athena M. Chen, Vincent L. Gao, Zhan-Guo Jacobsom, Kenneth A. TI Probing distal regions of the A(2B) adenosine receptor by quantitative structure-activity relationship Modeling of known and novel agonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; BINDING-SITE; BIOLOGICAL EVALUATION; 3,5-DIACYL-2,4-DIALKYLPYRIDINE DERIVATIVES; ANTAGONISTS; POTENT; LIGANDS; A(1); IDENTIFICATION; RECOGNITION AB The binding modes at the A(2B) adenosine receptor (AR) of 72 derivatives of adenosine and its 5'-N-methyluronamide with diverse substitutions at the 2 and N-6 positions were studied using a molecular modeling approach. The compounds in their receptor-docked conformations were used to build CoMFA and CoMSIA quantitative structure-activity relationship models. Various parameters, including different types of atomic charges, were examined. The best statistical parameters were obtained with a joint CoMFA and CoMSIA model: R-2 = 0.960, Q(2) = 0.676, SEE = 0.175, F = 158, and R-test(2) = 0.782 for an independent test set containing 18 compounds. On the basis of the modeling results. four novel adenosine analogues, having elongated or bulky substitutions at N-6 position and/or 2 position, were synthesized and evaluated biologically. All of the proposed compounds were potent, full agonists at the A(2B) AR in adenylate cyclase studies. Thus, in support of the modeling, bulky substitutions at both positions did not prevent A(2B) AR activation, which predicts separate regions for docking of these moieties. C1 [Ivanov, Andrei A.; Wang, Ben; Klutz, Athena M.; Chen, Vincent L.; Gao, Zhan-Guo; Jacobsom, Kenneth A.] NIDDKD, Mol Recognit Ctr, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. RP Jacobsom, KA (reprint author), NIDDKD, Mol Recognit Ctr, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS NR 53 TC 14 Z9 14 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD APR 10 PY 2008 VL 51 IS 7 BP 2088 EP 2099 DI 10.1021/jm701442d PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 284LY UT WOS:000254709100014 PM 18321038 ER PT J AU Milner, JD Brenchley, JM Laurence, A Freeman, AF Hill, BJ Elias, KM Kanno, Y Spalding, C Elloumi, HZ Paulson, ML Davis, J Hsu, A Asher, AI O'Shea, J Holland, SM Paul, WE Douek, DC AF Milner, Joshua D. Brenchley, Jason M. Laurence, Arian Freeman, Alexandra F. Hill, Brenna J. Elias, Kevin M. Kanno, Yuka Spalding, Christine Elloumi, Houda Z. Paulson, Michelle L. Davis, Joie Hsu, Amy Asher, Ava I. O'Shea, John Holland, Steven M. Paul, William E. Douek, Daniel C. TI Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome SO NATURE LA English DT Article ID HELPER T-CELLS; NEUTROPHIL RECRUITMENT; HOST-DEFENSE; IL-21; GENERATION; STAT3; ACTIVATION; EXPRESSION; CYTOKINE; INTERLEUKIN-17 AB The autosomal dominant hyper-IgE syndrome (HIES, 'Job's syndrome') is characterized by recurrent and often severe pulmonary infections, pneumatoceles, eczema, staphylococcal abscesses, mucocutaneous candidiasis, and abnormalities of bone and connective tissue(1,2). Mutations presumed to underlie HIES have recently been identified in stat3, the gene encoding STAT3 (signal transducer and activator of transcription 3) (refs 3, 4). Although impaired production of interferon-gamma and tumour-necrosis factor by T cells(5), diminished memory T-cell populations, decreased delayed-type-hypersensitivity responses and decreased in vitro lymphoproliferation in response to specific antigens(6) have variably been described, specific immunological abnormalities that can explain the unique susceptibility to particular infections seen in HIES have not yet been defined. Here we show that interleukin (IL)-17 production by T cells is absent in HIES individuals. We observed that ex vivo T cells from subjects with HIES failed to produce IL-17, but not IL-2, tumour-necrosis factor or interferon-gamma, on mitogenic stimulation with staphylococcal enterotoxin B or on antigenic stimulation with Candida albicans or streptokinase. Purified naive T cells were unable to differentiate into IL-17-producing (T(H)17) T helper cells in vitro and had lower expression of retinoid-related orphan receptor (ROR)-gamma t, which is consistent with a crucial role for STAT3 signalling in the generation of T(H)17 cells(7-14). T(H)17 cells have emerged as an important subset of helper T cells(15) that are believed to be critical in the clearance of fungal(16) and extracellular bacterial(17) infections. Thus, our data suggest that the inability to produce T(H)17 cells is a mechanism underlying the susceptibility to the recurrent infections commonly seen in HIES. C1 [Brenchley, Jason M.; Hill, Brenna J.; Asher, Ava I.; Douek, Daniel C.] NIAMSD, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Milner, Joshua D.; Paul, William E.] NIAMSD, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Laurence, Arian; Elias, Kevin M.; Kanno, Yuka; O'Shea, John] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Freeman, Alexandra F.; Spalding, Christine; Elloumi, Houda Z.; Paulson, Michelle L.; Davis, Joie; Hsu, Amy; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Elias, Kevin M.] Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA. RP Douek, DC (reprint author), NIAMSD, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM ddouek@nih.gov RI Laurence, Arian/A-8770-2009; Kanno, Yuka/B-5802-2013; OI Laurence, Arian/0000-0003-0942-8292; Kanno, Yuka/0000-0001-5668-9319; Elias, Kevin/0000-0003-1502-5553 FU Intramural NIH HHS [Z99 AI999999] NR 30 TC 594 Z9 610 U1 3 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 10 PY 2008 VL 452 IS 7188 BP 773 EP U11 DI 10.1038/nature06764 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 285QY UT WOS:000254792500050 PM 18337720 ER PT J AU Pearce, VP Sherrell, J Lou, Z Kopelovich, L Wright, WE Shay, JW AF Pearce, V. P. Sherrell, J. Lou, Z. Kopelovich, L. Wright, W. E. Shay, J. W. TI Immortalization of epithelial progenitor cells mediated by resveratrol SO ONCOGENE LA English DT Article DE telomerase; p53; progesterone; breast epithelial; aging ID BREAST-CANCER CELLS; TELOMERASE ACTIVITY; IN-VITRO; PROGESTERONE-RECEPTORS; MAMMARY-GLAND; P53 PROTEIN; ACTIVATION; EXPRESSION; TRANSFORMATION; PROLIFERATION AB Within the hierarchy of epithelial stem cells, normal progenitor cells may express regulated telomerase during renewal cycles of proliferation and differentiation. Discontinuous telomerase activity may promote increased renewal capacity of progenitor cells, while deregulated/ continuous telomerase activity may promote immortalization when differentiation and/ or senescent pathways are compromised. In the present work, we show that resveratrol activates, while progesterone inactivates, continuous telomerase activity within 24 h in subpopulations of human Li - Fraumeni syndrome- derived breast epithelial cells. Resveratrol results in immortalization of mixed progenitor cells with mutant p53, but not human epithelial cells with wild type p53. Our results demonstrate the potential for renewing progenitor cells with mutant p53 to immortalize after continuous telomerase expression when exposed to certain environmental compounds. Understanding the effects of telomerase modulators on endogenous telomerase activity in progenitor cells is relevant to the role of immortalization in the initiation and progression of cancer subtypes. C1 [Pearce, V. P.; Lou, Z.; Wright, W. E.; Shay, J. W.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. [Pearce, V. P.] Univ N Texas, Dept Pharmacol & Neurosci, UNT Hlth Sci Ctr Ft Worth, Ft Worth, TX USA. [Sherrell, J.] Univ Arizona, Sch Dent, Phoenix, AZ USA. [Kopelovich, L.] NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Shay, JW (reprint author), Univ Texas SW Med Ctr Dallas, Dept Cell Biol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Jerry.Shay@UTSouthwestern.edu RI Shay, Jerry/F-7878-2011 FU NCI NIH HHS [CN-05106, N01-CN43301, N01CN43301, P50 CA070907, P50 CA75907] NR 47 TC 19 Z9 19 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 APR 10 PY 2008 VL 27 IS 17 BP 2365 EP 2374 DI 10.1038/sj.onc.1210886 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 286KN UT WOS:000254844900001 PM 17968319 ER PT J AU Tsutsumi, S Scroggins, B Koga, F Lee, MJ Trepel, J Felts, S Carreras, C Neckers, L AF Tsutsumi, S. Scroggins, B. Koga, F. Lee, M-J Trepel, J. Felts, S. Carreras, C. Neckers, L. TI A small molecule cell-impermeant Hsp90 antagonist inhibits tumor cell motility and invasion SO ONCOGENE LA English DT Article DE heat shock protein 90; cell motility; cancer metastasis; molecularly targeted small molecules ID FOCAL ADHESION KINASE; CANCER CELLS; METASTASIS; MIGRATION; MELANOMA; EXPRESSION; GELDANAMYCIN; PHENOTYPES; SELECTION; ACTIN AB Heat shock protein 90 ( Hsp90) is a molecular chaperone that maintains function of numerous intracellular signaling nodes utilized by cancer cells for proliferation and survival. Hsp90 is also detected on the plasma membrane of tumor cells and its expression has been suggested to correlate with metastatic potential. Given the abundance and diverse functions of the intracellular pool of this protein, the precise contribution of cell surface Hsp90 to cell motility and tumor metastasis remains to be determined. In this study we utilized the small molecule DMAG- N- oxide, a novel cell- impermeable Hsp90 inhibitor, to specifically examine the role of cell surface Hsp90 in cell motility. We observed that, while not affecting intracellular Hsp90 function, DMAG- N- oxide significantly retarded tumor cell migration and integrin/extracellular matrix- dependent cytoskeletal reorganization. Concomitant with these findings, targeting cell surface Hsp90 significantly inhibited tumor cell motility and invasion in vitro, and had a dramatic impact on melanoma cell lung colonization in vivo. These data indicate that cell surface Hsp90 plays an important role in modulating cancer cell migration that is independent of the function of the intracellular Hsp90 pool, and that small molecule inhibitors of surface Hsp90 may provide a new approach to targeting the metastatic phenotype. C1 [Tsutsumi, S.; Scroggins, B.; Koga, F.; Neckers, L.] NCI, NIH, Urol Oncol Branch, Bethesda, MD 20892 USA. [Lee, M-J; Trepel, J.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Felts, S.] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN USA. [Felts, S.] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA. [Carreras, C.] Kosan Biosci, Hayward, CA USA. RP Neckers, L (reprint author), NCI, NIH, Urol Oncol Branch, 9000 ROckville Pike,Bldg 10-CRC,1-5940, Bethesda, MD 20892 USA. EM len@helix.nih.gov FU Intramural NIH HHS [Z01 SC006659-25, Z01 SC010074-12] NR 29 TC 76 Z9 79 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 10 PY 2008 VL 27 IS 17 BP 2478 EP 2487 DI 10.1038/sj.onc.1210897 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 286KN UT WOS:000254844900012 PM 17968312 ER PT J AU Arany, PR Rane, SG Roberts, AB AF Arany, P. R. Rane, S. G. Roberts, A. B. TI Smad3 deficiency inhibits v-ras-induced transformation by suppression of JNK MAPK signaling and increased farnesyl transferase inhibition SO ONCOGENE LA English DT Article DE TGF-beta 1; Smad3; JNK MAPK; Ras; malignant transformation; farnesyl transferase inhibition ID GROWTH-FACTOR-BETA; ONCOGENIC RAS; EXTRACELLULAR-MATRIX; CARCINOMA-CELLS; H-RAS; KINASE; PROTEIN; MECHANISM; PHOSPHORYLATION; FIBROBLASTS AB The ability of transforming growth factor-beta ( TGF- beta) to modulate various effects on distinct cell lineages has been a central feature of its multi- faceted nature. The purpose of this study was to access the effects of deletion of a key TGF- beta signal transducer, Smad3, on MAPK activation and v- Ras(Ha)- transformation of primary mouse embryonic. broblasts ( MEFs). We observe reduced TGF- beta 1 and v- ras(Ha) mediated activation of the JNK and ERK MAPK pathway upon ablation of Smad3. Further, Smad3-deficient MEFs demonstrate resistance to v- ras(Ha)- induced transformation while the absence of Smad3 results in increased inhibition of farnesyl transferase activity. Taken together, these observations demonstrate that the absence of Smad3 protects. broblasts from oncogenic transformation by ( i) augmenting farnesyl transferase inhibition and ( ii) suppressing the Ras - JNK MAPK pathway. These results provide new insights into the molecular mechanisms involved in v- Ras(Ha) oncogene- induced mesenchymal phenotypic transformation. C1 [Arany, P. R.; Rane, S. G.; Roberts, A. B.] NCI, NIH, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. [Rane, S. G.] NIDDK, NIH, Diabet Branch, Bethesda, MD 20892 USA. RP Arany, PR (reprint author), Harvard Univ, Harvard Sch Dent Med, 188 Longwood Ave,REB 203, Boston, MA 02115 USA. EM arany@fas.harvard.edu; ranes@mail.nih.gov FU Intramural NIH HHS NR 44 TC 14 Z9 15 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 10 PY 2008 VL 27 IS 17 BP 2507 EP 2512 DI 10.1038/sj.onc.1210889 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 286KN UT WOS:000254844900016 PM 17952112 ER PT J AU Kalueff, AV Ren-Patterson, RF LaPorte, JL Murphy, DL AF Kalueff, Allan V. Ren-Patterson, Renee F. LaPorte, Justin L. Murphy, Dennis L. TI Domain interplay concept in animal models of neuropsychiatric disorders: A new strategy for high-throughput neurophenotyping research SO BEHAVIOURAL BRAIN RESEARCH LA English DT Review DE genetic animal models; brain disorders; behavioral/psychiatric phenotypes; domain interplay; comorbidity; gene x environment interaction; mutant and transgenic animals ID TRANSPORTER KNOCKOUT MICE; OBSESSIVE-COMPULSIVE DISORDER; FACTOR BDNF GENE; SEROTONIN TRANSPORTER; BIPOLAR SPECTRUM; INBRED STRAINS; ANXIETY; DEPRESSION; AUTISM; PHENOTYPES AB Genetic and environmental factors play a key role in psychiatric disorders. While some disorders display exceptionally high heritability, others show gene x experience x personality interactions, contributing complexity to psychiatric phenotypes. As some brain disorders frequently overlap and co-occur (representing a continuum Or spectrum of phenomena), modern psychiatry is shifting front "artificial" heterogeneity to the recognition of common elements in the pathogenesis of emotional, personality and behavioral disorders. Genetic animal models of these disorders represent an important direction of research, and are widely used to explore the role of different genes in brain mechanisms. Several concepts (such as endophenotypes, gene x environment interactions, and cross-species trait genetics) have been suggested for animal experimentation in this field. Here we develop a new concept based on targeting the complex interplay between different behavioral domains, meant to foster high-throughput phenotyping and integrative modeling of psychiatric disorders. Published by Elsevier B.V. C1 [Kalueff, Allan V.; Ren-Patterson, Renee F.; LaPorte, Justin L.; Murphy, Dennis L.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, Bldg 10,Room 3D41,10 Ctr Dr,MSC 1264, Bethesda, MD 20892 USA. EM kalueva@mail.nih.gov FU Intramural NIH HHS NR 73 TC 44 Z9 44 U1 1 U2 2 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 APR 9 PY 2008 VL 188 IS 2 BP 243 EP 249 DI 10.1016/j.bbr.2007.11.011 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 277MT UT WOS:000254217700001 PM 18164476 ER PT J AU Nowotny, M Cerritelli, SM Ghirlando, R Gaidamakov, SA Crouch, RJ Yang, W AF Nowotny, Marcin Cerritelli, Susana M. Ghirlando, Rodolfo Gaidamakov, Sergei A. Crouch, Robert J. Yang, Wei TI Specific recognition of RNA/DNA hybrid and enhancement of human RNase H1 activity by HBD SO EMBO JOURNAL LA English DT Article DE dsRNA; processivity; RNA/DNA hybrid; RNase H; specificity ID DOUBLE-STRANDED-RNA; DSRNA-BINDING DOMAIN; N-TERMINAL DOMAIN; SACCHAROMYCES-CEREVISIAE; RIBONUCLEASE-III; STRUCTURAL BASIS; PROTEINS; DNA; REVEALS; HI AB Human RNase H1 contains an N-terminal domain known as dsRHbd for binding both dsRNA and RNA/DNA hybrid. We find that dsRHbd binds preferentially to RNA/DNA hybrids by over 25-fold and rename it as hybrid binding domain (HBD). The crystal structure of HBD complexed with a 12 bp RNA/DNA hybrid reveals that the RNA strand is recognized by a protein loop, which forms hydrogen bonds with the 2'-OH groups. The DNA interface is highly specific and contains polar residues that interact with the phosphate groups and an aromatic patch that appears selective for binding deoxyriboses. HBD is unique relative to non-sequence-specific dsDNA- and dsRNA-binding domains because it does not use positive dipoles of alpha-helices for nucleic acid binding. Characterization of full-length enzymes with defective HBDs indicates that this domain dramatically enhances both the specific activity and processivity of RNase H1. Similar activity enhancement by small substrate-binding domains linked to the catalytic domain likely occurs in other nucleic acid enzymes. C1 [Nowotny, Marcin; Ghirlando, Rodolfo; Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Cerritelli, Susana M.; Gaidamakov, Sergei A.; Crouch, Robert J.] NICHHD, Lab Mol Genet, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM Wei.Yang@nih.gov RI Ghirlando, Rodolfo/A-8880-2009; Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU Intramural NIH HHS NR 33 TC 34 Z9 34 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD APR 9 PY 2008 VL 27 IS 7 BP 1172 EP 1181 DI 10.1038/emboj.2008.44 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 292UJ UT WOS:000255291300023 PM 18337749 ER PT J AU Howard, BV Roman, MJ Devereux, RB Fleg, JL Galloway, JM Henderson, JA Howard, WJ Lee, ET Mete, M Poolaw, B Ratner, RE Russell, M Silverman, A Stylianou, M Umans, JG Wang, WY Weir, MR Weissman, NJ Wilson, C Yeh, F Zhu, JH AF Howard, Barbara V. Roman, Mary J. Devereux, Richard B. Fleg, Jerome L. Galloway, James M. Henderson, Jeffrey A. Howard, Wm. James Lee, Elisa T. Mete, Mihriye Poolaw, Bryce Ratner, Robert E. Russell, Marie Silverman, Angela Stylianou, Mario Umans, Jason G. Wang, Wenyu Weir, Matthew R. Weissman, Neil J. Wilson, Charlton Yeh, Fawn Zhu, Jianhui TI Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes - The SANDS randomized trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; INTIMA-MEDIA THICKNESS; PLACEBO-CONTROLLED TRIAL; CONVERTING-ENZYME-INHIBITOR; COLESTIPOL-NIACIN THERAPY; TREATMENT PANEL-III; CARDIOVASCULAR-DISEASE; CAROTID ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION AB Context Individuals with diabetes are at increased risk for cardiovascular disease ( CVD), but more aggressive targets for risk factor control have not been tested. Objective To compare progression of subclinical atherosclerosis in adults with type 2 diabetes treated to reach aggressive targets of low- density lipoprotein cholesterol ( LDL- C) of 70 mg/ dL or lower and systolic blood pressure ( SBP) of 115 mm Hg or lower vs standard targets of LDL- C of 100 mg/ dL or lower and SBP of 130 mm Hg or lower. Design, Setting, and Participants A randomized, open- label, blinded- to- end point, 3- year trial from April 2003- July 2007 at 4 clinical centers in Oklahoma, Arizona, and South Dakota. Participants were 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events. Interventions Participants were randomized to aggressive ( n= 252) vs standard ( n= 247) treatment groups with stepped treatment algorithms defined for both. Main Outcome Measures Primary end point was progression of atherosclerosis measured by common carotid artery intimal medial thickness ( IMT). Secondary end points were other carotid and cardiac ultrasonographic measures and clinical events. Results Mean target LDL- C and SBP levels for both groups were reached and maintained. Mean ( 95% confidence interval) levels for LDL- C in the last 12 months were 72 ( 69- 75) and 104 ( 101- 106) mg/ dL and SBP levels were 117 ( 115- 118) and 129 ( 128130) mm Hg in the aggressive vs standard groups, respectively. Compared with baseline, IMT regressed in the aggressive group and progressed in the standard group (- 0.012 mm vs 0.038 mm; P <. 001); carotid arterial cross- sectional area also regressed (- 0.02 mm(2) vs 1.05 mm(2); P <. 001); and there was greater decrease in left ventricular mass index (- 2.4 g/m(2.7) vs - 1.2 g/m(2.7); P =. 03) in the aggressive group. Rates of adverse events ( 38.5% and 26.7%; P=. 005) and serious adverse events ( n= 4 vs 1; P=. 18) related to blood pressure medications were higher in the aggressive group. Clinical CVD events ( 1.6/ 100 and 1.5/ 100 person- years; P=. 87) did not differ significantly between groups. Conclusions Reducing LDL- C and SBP to lower targets resulted in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes. Clinical events were lower than expected and did not differ significantly between groups. Further follow- up is needed to determine whether these improvements will result in lower long- term CVD event rates and costs and favorable risk- benefit outcomes. Trial Registration clinicaltrials. gov Identifier: NCT00047424. C1 [Howard, Barbara V.; Mete, Mihriye; Ratner, Robert E.; Silverman, Angela; Umans, Jason G.; Weissman, Neil J.; Zhu, Jianhui] MedStar Res Inst, Hyattsville, MD 20783 USA. [Roman, Mary J.; Devereux, Richard B.] Weill Cornell Med Coll, New York, NY USA. [Fleg, Jerome L.; Stylianou, Mario] NHLBI, Bethesda, MD 20892 USA. [Galloway, James M.] Univ Arizona, Hlth Sci Ctr, Tucson, AZ USA. [Henderson, Jeffrey A.] Black Hills Ctr Amer Indian Hlth, Rapid City, SD USA. [Howard, Wm. James] Washington Hosp Ctr, Washington, DC 20010 USA. [Lee, Elisa T.; Wang, Wenyu; Yeh, Fawn] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Poolaw, Bryce] Lawton Indian Hosp, Lawton, OK USA. [Russell, Marie; Wilson, Charlton] Phoenix Indian Med Ctr, Phoenix, AZ USA. [Weir, Matthew R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Howard, BV (reprint author), MedStar Res Inst, 6495 New Hampshire Ave,Suite 201, Hyattsville, MD 20783 USA. EM barbara.v.howard@medstar.net FU NHLBI NIH HHS [U01 HL067031-01A1, 1U01 HL67031-01A1, U01 HL067031] NR 73 TC 136 Z9 146 U1 0 U2 2 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 APR 9 PY 2008 VL 299 IS 14 BP 1678 EP 1689 DI 10.1001/jama.299.14.1678 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 285AL UT WOS:000254749600024 PM 18398080 ER PT J AU Borer, JS Gordon, DJ Geller, NL AF Borer, Jeffrey S. Gordon, David J. Geller, Nancy L. TI When should data and safety monitoring committees share interim results in cardiovascular trials? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CLINICAL-TRIAL; BENEFIT C1 [Gordon, David J.; Geller, Nancy L.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Borer, Jeffrey S.] Cornell Univ, Weill Cornell Med Coll, New York, NY USA. RP Geller, NL (reprint author), NHLBI, Off Biostat Res, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM gellern@nhlbi.nih.gov NR 9 TC 9 Z9 9 U1 0 U2 1 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 APR 9 PY 2008 VL 299 IS 14 BP 1710 EP 1712 DI 10.1001/jama.299.14.1710 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 285AL UT WOS:000254749600027 PM 18398083 ER PT J AU Moody, TW Pradhan, T Mantey, SA Jensen, RT Dyba, M Moody, D Tarasova, NI Michejda, CJ AF Moody, Terry W. Pradhan, Tapas Mantey, Samuel A. Jensen, Robert T. Dyba, Marcin Moody, Deborah Tarasova, Nadya I. Michejda, Christopher J. TI Bombesin marine toxin conjugates inhibit the growth of lung cancer cells SO LIFE SCIENCES LA English DT Article DE bombesin; dolastatin; hemiasterlin; lung cancer ID GASTRIN-RELEASING-PEPTIDE; HIGH-AFFINITY; RECEPTOR SUBTYPES; DOLASTATIN 10; NEUROMEDIN-B; HEMIASTERLIN; SOMATOSTATIN; CARCINOMA; ANALOGS; CLONING AB Hemiasterlin (Hem) and dolastatin (Dol) are marine natural products which are cytotoxic for cancer cells. Hem, a tripeptide, and Dol, a hexapeptide, were conjugated with linkers (L) to the universal BB agonist DPhe-Gln-Trp-Ala-Val-beta Ala-His-Phe-Nle-NH2(BA1) and the effects of the Hem-BB and Dol-BB conjugates investigated on NCI-H1299 lung cancer cells. Hem-LA-BA1 and Hem-LB-BA1 inhibited specific (I-125-Tyr(4)) BB binding to NCI-H1299 cells, which have 13132 receptors (R), with IC50 values of 15 and 25 nM, respectively. Addition of Hem-LA-BA1 and Hem-LB-BA1 to Fura-2 AM loaded cells containing BB2R, caused elevated cytosolic Ca2+. In a growth assay, Hem-LA-BA1 and Hem-LB-BA1 inhibited the proliferation of NCI-H1299 cells. Dol-succinamide (Dols)-LD-BA1 and Dols-LE-BA1 bound with high affinity to NCI-H1299 cells and elevated cytosolic Ca2+, but did not inhibit the proliferation of NCI-H1299 cells. Also, Hem-LA-BA1 inhibited I-125-DTyr-Gln-Trp-Ala-Val-beta Ala-His-Phe-Nle-NH2 (BA2) binding to Balb/3T3 cells transfected with BB1R BB2R as well as with BRS-3 with IC50 values of 130, 8, and 540 nM, respectively. These results show that Hem-BB conjugates are cytotoxic for cancer cells containing BB2R. Published by Elsevier Inc. C1 [Moody, Terry W.] NCI Off, CCR, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Pradhan, Tapas; Mantey, Samuel A.; Jensen, Robert T.] NIDDK, NIH, Digest Dis Branch, Bethesda, MD 20892 USA. [Moody, Deborah; Tarasova, Nadya I.; Michejda, Christopher J.] NCI, Struct Biophys Lab, Mol Aspects Drug Design Sect, Frederick, MD 21702 USA. RP Moody, TW (reprint author), NCI Off, CCR, Dept Hlth & Human Serv, Bldg 31,Rm 4A48,31 Ctr Dr, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov OI Dyba, Marcin/0000-0001-6311-6877 FU Intramural NIH HHS [Z99 CA999999] NR 36 TC 7 Z9 7 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 9 PY 2008 VL 82 IS 15-16 BP 855 EP 861 DI 10.1016/j.lfs.2008.01.019 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 292MA UT WOS:000255269000006 PM 18336841 ER PT J AU Palkovits, M Harvey-White, J Liu, J Kovacs, ZS Bobest, M Lovas, G Bago, AG Kunos, G AF Palkovits, M. Harvey-White, J. Liu, J. Kovacs, Z. S. Bobest, M. Lovas, G. Bago, A. G. Kunos, G. TI Regional distribution and effects of postmortal delay on endocannabinoid content of the human brain SO NEUROSCIENCE LA English DT Article DE anandamide; 2-arachidonoylglycerol; brain microdissection; neurosurgical dissections ID ACID AMIDE HYDROLASE; CANNABINOID RECEPTOR-LIGAND; ENDOGENOUS CANNABINOIDS; MULTIPLE-SCLEROSIS; RAT-BRAIN; ANANDAMIDE; MODEL; MICE; 2-ARACHIDONOYLGLYCEROL; AGE AB Tissue levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have been determined in 16 regions and nuclei from human brains, using liquid chromatography/ in-line mass spectrometry. Measurements in brain samples stored at - 80 degrees C for 2 months to 13 years indicated that endocannabinoids were stable under such conditions. In contrast, the postmortal delay had a strong effect on brain endocannabinoid levels, as documented in brain samples microdissected and frozen 1 - 6 h postmortem, and in neurosurgical samples 0, 5, 30, 60, 180 and 360 min after their removal from the brain. The tissue levels of AEA increased continuously and in a region-dependent manner from 1 h after death, increasing about sevenfold by 6 h postmortem. In contrast, concentrations of 2-AG, which were 10 - 100 times higher in human brain regions than those of AEA, rapidly declined: within the first hour, 2-AG levels dropped to 25 - 35% of the initial ('0 min') value, thereafter they remained relatively stable. As analyzed in samples removed 1 - 1.5 h postmortem, AEA levels ranged from a high of 96.3 fmol/mg tissue in the nucleus accumbens to a low of 25.0 fmol/mg in the cerebellum. 2-AG levels varied eightfold, from 8.6 pmol/mg in the lateral hypothalamus to 1.1 pmol/mg in the nucleus accumbens. Relative levels of AEA and 2-AG varied from region to region, with the 2-AG:AEA ratio being high in the sensory spinal trigeminal nucleus (140:1), the spinal dorsal horn (136:1) and the lateral hypothalamus (98:1) and low in the nucleus accumbens (16:1) and the striatum (31:1). The results highlight the pitfall of analyzing endocannabinoid content in brain samples of variable postmortal delay, and document differential distribution of the two main endocannabinoids in the human brain. (c) 2008 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Palkovits, M.] Semmelweis Univ, Neurimorphol & Neuroendocrine Res Lab, H-1094 Budapest, Hungary. [Palkovits, M.] Hungarian Acad Sci, H-1094 Budapest, Hungary. [Harvey-White, J.; Liu, J.; Kunos, G.] NIAAA, NIH, Lab Physiol Studies, Bethesda, MD 20892 USA. [Kovacs, Z. S.] Univ W Hungary, Dept Zool, H-9700 Szombathely, Hungary. [Bobest, M.] Markusovszky Hosp, H-9700 Szombathely, Hungary. [Lovas, G.] Semmelweis Univ, Dept Neurol, H-1083 Budapest, Hungary. [Bago, A. G.] Natl Inst Neurosurg, H-1145 Budapest, Hungary. RP Palkovits, M (reprint author), Tuzolto U 58, H-1094 Budapest, Hungary. EM palkovits@ana.sote.hu RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 FU Intramural NIH HHS [Z01 AA000350-07] NR 29 TC 28 Z9 28 U1 0 U2 7 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 APR 9 PY 2008 VL 152 IS 4 BP 1032 EP 1039 DI 10.1016/j.neuroscience.2008.01.034 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 290WF UT WOS:000255152800017 PM 18343585 ER PT J AU Paletzki, RF Myakishev, MV Polesskaya, O Orosz, A Hyman, SE Vinson, C AF Paletzki, R. F. Myakishev, M. V. Polesskaya, O. Orosz, A. Hyman, S. E. Vinson, C. TI Inhibiting activator protein-1 activity alters cocaine-induced gene expression and potentiates sensitization SO NEUROSCIENCE LA English DT Article DE A-FOS; addiction; sensitization; gene expression ID GENOME-WIDE SEARCH; NUCLEUS-ACCUMBENS; RAT STRIATUM; DNA-BINDING; DELTA-FOSB; C-FOS; BEHAVIORAL PLASTICITY; DOPAMINE TRANSMISSION; SUBSTANCE DEPENDENCE; MATRIX COMPARTMENTS AB We have expressed A-FOS, an inhibitor of activator protein-1 (AP-1) DNA binding, in adult mouse striatal neurons. We observed normal behavior including locomotion and exploratory activities. Following a single injection of cocaine, locomotion increased similarly in both the A-FOS expressing and littermate controls. However, following repeated injections of cocaine, the A-FOS expressing mice showed increased locomotion relative to littermate controls, an increase that persisted following a week of withdrawal and subsequent cocaine administration. These results indicate that AP-1 suppresses this behavioral response to cocaine. We analyzed mRNA from the striatum before and 4 and 24 h after a single cocaine injection in both A-FOS and control striata using Affymetrix microarrays (430 2.0 Array) to identify genes mis-regulated by A-FOS that may mediate the increased locomotor sensitization to cocaine. A-FOS expression did not change gene expression in the basal state or 4 h following cocaine treatment relative to controls. However, 24 h after an acute cocaine treatment, 84 genes were identified that were differentially expressed between the A-FOS and control mice. Fifty-six genes are down-regulated while 28 genes are up-regulated including previously identified candidates for addiction including brain-derived neurotrophic factor and period homolog 1. Using a random sample of identified genes, quantitative PCR was used to verify the microarray studies. The chromosomal location of these 84 genes was compared with human genome scans of addiction to identify potential genes in humans that are involved in addiction. Published by Elsevier Ltd on behalf of IBRO. C1 [Paletzki, R. F.; Hyman, S. E.] NINDS, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. [Myakishev, M. V.; Orosz, A.; Vinson, C.] NCI, Lab Metab, Bethesda, MD 20892 USA. [Polesskaya, O.] George Mason Univ, Dept Psychol, Manassas, VA 20110 USA. RP Vinson, C (reprint author), NIMH, Lab Syst Neurosci, NIH, Bldg 35,Room 3A1014, Bethesda, MD 20892 USA. EM Vinsonc@dc37a.nci.nih.gov FU Intramural NIH HHS [Z99 CA999999, Z01 BC005271-16] NR 64 TC 7 Z9 8 U1 0 U2 0 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 APR 9 PY 2008 VL 152 IS 4 BP 1040 EP 1053 DI 10.1016/j.neuroscience.2008.01.045 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 290WF UT WOS:000255152800018 PM 18355967 ER PT J AU Bharti, N Xia, YC Bjornstad, ON Grenfell, BT AF Bharti, Nita Xia, Yingcun Bjornstad, Ottar N. Grenfell, Bryan T. TI Measles on the Edge: Coastal Heterogeneities and Infection Dynamics SO PLOS ONE LA English DT Article AB Mathematical models can help elucidate the spatio-temporal dynamics of epidemics as well as the impact of control measures. The gravity model for directly transmitted diseases is currently one of the most parsimonious models for spatial epidemic spread. This model uses distance-weighted, population size-dependent coupling to estimate host movement and disease incidence in metapopulations. The model captures overall measles dynamics in terms of underlying human movement in pre-vaccination England and Wales (previously established). In spatial models, edges often present a special challenge. Therefore, to test the model's robustness, we analyzed gravity model incidence predictions for coastal cities in England and Wales. Results show that, although predictions are accurate for inland towns, they significantly underestimate coastal persistence. We examine incidence, outbreak seasonality, and public transportation records, to show that the model's inaccuracies stem from an underestimation of total contacts per individual along the coast. We rescue this predicted 'edge effect' by increasing coastal contacts to approximate the number of per capita inland contacts. These results illustrate the impact of 'edge effects' on epidemic metapopulations in general and illustrate directions for the refinement of spatiotemporal epidemic models. C1 [Bharti, Nita; Bjornstad, Ottar N.; Grenfell, Bryan T.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Xia, Yingcun] Natl Univ Singapore, Dept Stat & Appl Probability, Singapore, Singapore. [Bjornstad, Ottar N.] Penn State Univ, Dept Entomol, University Pk, PA USA. [Bjornstad, Ottar N.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD USA. [Bharti, Nita; Bjornstad, Ottar N.; Grenfell, Bryan T.] Penn State Univ, Ctr Infect Dis Dynamics, University Pk, PA USA. RP Bharti, N (reprint author), Penn State Univ, Dept Biol, University Pk, PA 16802 USA. EM nita@psu.edu RI Bjornstad, Ottar/I-4518-2012 FU department of biology at Penn State; Center for Infectious Disease Dynamics FX Funding was provided by the department of biology at Penn State and the Center for Infectious Disease Dynamics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript NR 22 TC 10 Z9 10 U1 0 U2 0 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 APR 9 PY 2008 VL 3 IS 4 AR e1941 DI 10.1371/journal.pone.0001941 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 370XD UT WOS:000260795500018 PM 18398467 ER PT J AU Muftuoglu, M Kusumoto, R Speina, E Beck, G Cheng, WH Bohr, VA AF Muftuoglu, Meltem Kusumoto, Rika Speina, Elzbieta Beck, Gad Cheng, Wen-Hsing Bohr, Vilhelm A. TI Acetylation Regulates WRN Catalytic Activities and Affects Base Excision DNA Repair SO PLOS ONE LA English DT Article AB Background: The Werner protein (WRN), defective in the premature aging disorder Werner syndrome, participates in a number of DNA metabolic processes, and we have been interested in the possible regulation of its function in DNA repair by post-translational modifications. Acetylation mediated by histone acetyltransferases is of key interest because of its potential importance in aging, DNA repair and transcription. Methodology/Principal Findings: Here, we have investigated the p300 acetylation mediated changes on the function of WRN in base excision DNA repair (BER). We show that acetylation of WRN increases in cells treated with methyl methanesulfonate (MMS), suggesting that acetylation of WRN may play a role in response to DNA damage. This hypothesis is consistent with our findings that acetylation of WRN stimulates its catalytic activities in vitro and in vivo, and that acetylated WRN enhances pol beta-mediated strand displacement DNA synthesis more than unacetylated WRN. Furthermore, we show that cellular exposure to the histone deacetylase inhibitor sodium butyrate stimulates long patch BER in wild type cells but not in WRN depleted cells, suggesting that acetylated WRN participates significantly in this process. Conclusion/Significance: Collectively, these results provide the first evidence for a specific role of p300 mediated WRN acetylation in regulating its function during BER. C1 [Muftuoglu, Meltem; Kusumoto, Rika; Speina, Elzbieta; Beck, Gad; Cheng, Wen-Hsing; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Speina, Elzbieta] Polish Acad Sci, Inst Biochem & Biophys, Warsaw, Poland. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov NR 57 TC 19 Z9 19 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 APR 9 PY 2008 VL 3 IS 4 AR e1918 DI 10.1371/journal.pone.0001918 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 370XD UT WOS:000260795500005 PM 18398454 ER PT J AU Imoto, S Bransfield, LA Croteau, DL Van Houten, B Greenberg, MM AF Imoto, Shuhei Bransfield, Leslie A. Croteau, Deborah L. Van Houten, Bennett Greenberg, Marc M. TI DNA tandem lesion repair by strand displacement synthesis and nucleotide excision repair SO BIOCHEMISTRY LA English DT Article ID COLI ENDONUCLEASE III; DOUBLE-BASE LESIONS; CROSS-LINK LESIONS; ESCHERICHIA-COLI; POLYMERASE-BETA; UVRABC NUCLEASE; EXONUCLEASE-III; DAMAGING AGENTS; 2-DEOXYRIBONOLACTONE LESION; IRRADIATED DNA AB DNA tandem lesions are comprised of two contiguously damaged nucleotides. This subset of clustered lesions is produced by a variety of oxidizing agents, including ionizing radiation. Clustered lesions can inhibit base excision repair (BER). We report the effects of tandem lesions composed of a thymine glycol and a 5'-adjacent 2-deoxyribonolactone (LTg) or tetrahydrofuran abasic site (FTg). Some BER enzymes that act on the respective isolated lesions do not accept the tandem lesion as a substrate. For instance, endonuclease III (Nth) does not excise thymine glycol (Tg) when it is part of either tandem lesion. Similarly, endonuclease IV (Nfo) does not incise L or F when they are in tandem with Tg. Long-patch BER overcomes inhibition by the tandem lesion. DNA polymerase beta (Po1 beta) carries out strand displacement synthesis, following APE1 incision of the abasic site. Po1 beta activity is enhanced by flap endonuclease (FEN1), which cleaves the resulting flap. The tandem lesion is also incised by the bacterial nucleotide excision repair system UvrABC with almost the same efficiency as an isolated Tg. These data reveal two solutions that DNA repair systems can use to counteract the formation of tandem lesions. C1 [Imoto, Shuhei; Bransfield, Leslie A.; Greenberg, Marc M.] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA. [Croteau, Deborah L.; Van Houten, Bennett] Natl Inst Hlth, NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Greenberg, MM (reprint author), Johns Hopkins Univ, Dept Chem, 3400 N Charles St, Baltimore, MD 21218 USA. EM mgreenberg@jhu.edu FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM063028-08, GM-063028, R01 GM063028, R01 GM063028-07] NR 65 TC 32 Z9 33 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 APR 8 PY 2008 VL 47 IS 14 BP 4306 EP 4316 DI 10.1021/bi7021427 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 282WL UT WOS:000254597800014 PM 18341293 ER PT J AU Najjar, SS Scuteri, A Shetty, V Wright, JG Muller, DC Fleg, JL Spurgeon, HP Ferrucci, L Lakatta, EG AF Najjar, Samer S. Scuteri, Angelo Shetty, Veena Wright, Jeanette G. Muller, Denis C. Fleg, Jerome L. Spurgeon, Harold P. Ferrucci, Luigi Lakatta, Edward G. TI Pulse wave velocity is an independent predictor of the longitudinal increase in systolic blood pressure and of incident hypertension in the Baltimore longitudinal study of aging SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ARTERIAL STIFFNESS; AORTIC STIFFNESS; CARDIOVASCULAR MORTALITY; YOUNG-ADULTS; RISK; AGE; PROGRESSION; DISEASE; REFLECTION; MODELS AB Objectives This study sought to evaluate whether pulse wave velocity (PWV), a noninvasive index of arterial stiffness, is a predictor of the longitudinal changes in systolic blood pressure (SBP) and of incident hypertension. Background Although arterial stiffness is believed to underlie, in part, the age-associated changes in SBP, particularly at older ages, few longitudinal studies in humans have examined the relationship between arterial stiffness and blood pressure. Methods Pulse wave velocity was measured at baseline in 449 normotensive or untreated hypertensive volunteers (age 53 +/- 17 years). Repeated measurements of blood pressure were performed during an average follow-up of 4.9 +/- 2.5 years. Results After adjusting for covariates including age, body mass index, and mean arterial pressure, linear mixed effects regression models showed that PWV was an independent determinant of the longitudinal increase in SBP (p = 0.003 for the interaction term with time). In a subset of 306 subjects who were normotensive at baseline, hypertension developed in 105 (34%) during a median follow-up of 4.3 years (range 2 to 12 years). By stepwise Cox proportional hazards models, PWV was an independent predictor of incident hypertension (hazard ratio 1.10 per 1 m/s increase in PWV, 95% confidence interval 1.00 to 1.30, p = 0.03) in individuals with a follow-up duration greater than the median. Conclusions Pulse wave velocity is an independent predictor of the longitudinal increase in SBP and of incident hypertension. This suggests that PWV could help identify normotensive individuals who should be targeted for the implementation of interventions aimed at preventing or delaying the progression of subclinical arterial stiffening and the onset of hypertension. C1 [Najjar, Samer S.; Scuteri, Angelo; Shetty, Veena; Spurgeon, Harold P.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Scuteri, Angelo] UO Geriatria, INRCA, Rome, Italy. [Wright, Jeanette G.; Muller, Denis C.; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Fleg, Jerome L.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Najjar, SS (reprint author), Harbor Hosp, NIA, ASTRA Unit, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM NajjarSa@mail.nih.gov FU Intramural NIH HHS [Z01 AG000015-49] NR 29 TC 158 Z9 175 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 8 PY 2008 VL 51 IS 14 BP 1377 EP 1383 DI 10.1016/j.jacc.2007.10.065 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 284AL UT WOS:000254677500009 PM 18387440 ER PT J AU Gegonne, A Weissman, JD Lu, HX Zhou, MS Dasguptat, A Ribble, R Brady, JN Singer, DS AF Gegonne, Anne Weissman, Jocelyn D. Lu, Hanxin Zhou, Meisheng Dasguptat, Arindam Ribble, Robert Brady, John N. Singer, Dinah S. TI TFIID component TAF7 functionally interacts with both TFIIH and P-TEFb SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MHC class I genes; regulation; transcription initiation ID RNA-POLYMERASE-II; VIRUS TYPE-1 TRANSCRIPTION; CARBOXYL-TERMINAL DOMAIN; HEAT-SHOCK GENES; ACETYLTRANSFERASE ACTIVITY; ACTIVATING KINASE; IN-VIVO; PHOSPHORYLATION; ELONGATION; TAF(II)250 AB Transcription consists of a series of highly regulated steps: assembly of the preinitiation complex (PIC) at the promoter, initiation, elongation, and termination. PIC assembly is nucleated by TRID, a complex composed of the TATA-binding protein (TBP) and a series of TBP-associated factors (TAFs). One component, TAF7, is incorporated in the PIC through its interaction with TFIID but is released from TFIID upon transcription initiation. We now report that TAF7 interacts with the transcription factors, TFIIH and P-TEFb, resulting in the inhibition of their Pol II CTD kinase activities. Importantly, in in vitro transcription reactions, TAF7 inhibits steps after PIC assembly and formation of the first phosphodiester bonds. Further, in vivo TAF7 coelongates with P-TEFb and Pol II downstream of the promoter. We propose a model in which TAF7 contributes to the regulation of the transition from PIC. assembly to initiation and elongation. C1 [Gegonne, Anne; Weissman, Jocelyn D.; Lu, Hanxin; Singer, Dinah S.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Zhou, Meisheng; Dasguptat, Arindam; Ribble, Robert; Brady, John N.] NCI, Tumor Virus Biol Lab, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dinah.singer@nih.gov NR 36 TC 19 Z9 19 U1 0 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 APR 8 PY 2008 VL 105 IS 14 BP 5367 EP 5372 DI 10.1073/pnas.0801637105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 287CG UT WOS:000254893600017 PM 18391197 ER PT J AU Hadj-Bouziane, F Bell, AH Knusten, TA Ungerleider, LG Tootell, RBH AF Hadj-Bouziane, Fadila Bell, Andrew H. Knusten, Tamara A. Ungerleider, Leslie G. Tootell, Roger B. H. TI Perception of emotional expressions is independent of face selectivity in monkey inferior temporal cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amygdala; emotion; valence; fMRl ID SURFACE-BASED ANALYSIS; FACIAL EXPRESSIONS; VISUAL-CORTEX; CONTRAST AGENT; HUMAN AMYGDALA; RESPONSES; NEURONS; MACAQUE; IDENTITY; COMMUNICATION AB The ability to perceive and differentiate facial expressions is vital for social communication. Numerous functional MRI (fMR1) studies in humans have shown enhanced responses to faces with different emotional valence, in both the amygdala and the visual cortex. However, relatively few studies have examined how valence influences neural responses in monkeys, thereby limiting the ability to draw comparisons across species and thus understand the underlying neural mechanisms. Here we tested the effects of macaque facial expressions on neural activation within these two regions using fMR1 in three awake, behaving monkeys. Monkeys maintained central fixation while blocks of different monkey facial expressions were presented. Four different facial expressions were tested: (i) neutral, (it) aggressive (open-mouthed threat), (fil) fearful (fear grin), and (iv) submissive (lip smack). Our results confirmed that both the amygdala and the inferior temporal cortex in monkeys are modulated by facial expressions. As in human fMR1, fearful expressions evoked the greatest response in monkeys-even though fearful expressions are physically dissimilar in humans and macaques. Furthermore, we found that valence effects were not uniformly distributed over the inferior temporal cortex. Surprisingly, these valence maps were independent of two related functional maps: (i) the map of -"face-selective" regions (faces versus non-face objects) and (it) the map of "face-responsive" regions (faces versus scrambled images). Thus, the neural mechanisms underlyingface perception and valence perception appear to be distinct. C1 [Hadj-Bouziane, Fadila; Bell, Andrew H.; Ungerleider, Leslie G.; Tootell, Roger B. H.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Knusten, Tamara A.; Tootell, Roger B. H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Hadj-Bouziane, F (reprint author), NIMH, Lab Brain & Cognit, NIH, 49 Convent Dr,Bldg 49-1B80, Bethesda, MD 20892 USA. EM hadjf@mail.nih.gov; ungerlel@mail.nih.gov RI Hadj-Bouziane, Fadila/A-1180-2013; OI Bell, Andrew/0000-0001-8420-4622 FU Intramural NIH HHS; NEI NIH HHS [R01 EY017081, R01 EY017081-01A1, R01 EY017081-02, R01 EY017081-03]; NIMH NIH HHS [R01 MH67529, R01 MH067529] NR 42 TC 50 Z9 50 U1 2 U2 6 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 APR 8 PY 2008 VL 105 IS 14 BP 5591 EP 5596 DI 10.1073/pnas.0800489105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 287CG UT WOS:000254893600055 PM 18375769 ER PT J AU Zhou, XM Ferraris, JD Dimitrieva, NI Liu, YS Burg, MB AF Zhou, Xiaoming Ferraris, Joan D. Dimitrieva, Natalia I. Liu, Yusen Burg, Maurice B. TI MKP-1 inhibits high NaCl-induced activation of p38 but does not inhibit the activation of TonEBP/OREBP: Opposite roles of p38 alpha and p38 delta SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hypertonicity; reactive oxygen species; transcription; HEK293 cells; mIMCD3 cells ID MAP KINASE PHOSPHATASE-1; OSMOTIC RESPONSE ELEMENT; TRANSCRIPTION FACTOR TONEBP/OREBP; OXYGEN SPECIES CONTRIBUTE; PROTEIN-KINASE; KIDNEY-CELLS; CATALYTIC ACTIVATION; DNA-DAMAGE; IN-VIVO; EXPRESSION AB High NaCl rapidly activates p38 MAPK by phosphorylating it, the phosphorylation presumably being regulated by a balance of kinases and phosphatases. Kinases are known, but the phosphatases are uncertain. Our initial purpose was to identify the phosphatases. We find that in HEK293 cells transient overexpression of MAPK phosphatase-1 (MKP-1), a dual-specificity phosphatase, inhibits high NaCl-induced phosphorylation of p38, and that overexpression of a dominant negative mutant of MKP-1 does the opposite. High NaCl lowers MKP-1 activity by increasing reactive oxygen species, which directly inhibit MKP-1, and by reducing binding of MKP-1 to p38. Because inhibition of p38 is reported to reduce hypertonicity-induced activation of the osmoprotective transcription factor, TonEBP/OREBP, we anticipated that MKP-1 expression might also. However, overexpression of MKP-1 has no significant effect on Ton EBP/OREBP activity. This paradox is explained by opposing effects of p38 alpha and p38 delta, both of which are activated by high NaCl and inhibited by MKP-1. Thus, we find that overexpression of p38 alpha increases high NaCl-induced TonEBP/OREBP activity, but overexpression of p38 delta reduces it. Also, siRNA-mediated knockdown of p38 delta enhances the activation of TonEBP/OREBP. We conclude that high NaCl inhibits MKP-1, which contributes to the activation of p38. However, opposing actions of p38 alpha and p38 delta negate any effect on TonEBP/OREBP activity. Thus, activation of p38 isoforms by hypertonicity does not contribute to activation of TonEBP/OREBP because of opposing effects of p38 alpha and p38 delta, and effects of inhibitors of p38 depend on which isoform is affected, which can be misleading. C1 [Ferraris, Joan D.; Dimitrieva, Natalia I.; Burg, Maurice B.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. [Zhou, Xiaoming] Uniformed Serv Univ Hlth Sci, Div Nephrol, Dept Med, Bethesda, MD 20814 USA. [Liu, Yusen] Ohio State Univ, Coll Med, Ctr Perinatal Res, Res Inst,Nationwide Childrens Hosp,Dept Pediat, Columbus, OH 43205 USA. RP Burg, MB (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. EM burgm@nhlbi.nih.gov RI Dmitrieva, Natalia/A-2924-2013; Liu, Yusen/E-3527-2011 OI Dmitrieva, Natalia/0000-0001-8074-6950; FU Intramural NIH HHS NR 36 TC 24 Z9 25 U1 0 U2 0 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 APR 8 PY 2008 VL 105 IS 14 BP 5620 EP 5625 DI 10.1073/pnas.0801453105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 287CG UT WOS:000254893600060 PM 18367666 ER PT J AU Espada, J Varela, I Flores, I Ugalde, AP Cadinanos, J Pendas, AM Stewart, CL Tryggvason, K Blasco, MA Freije, JMP Lopez-Otin, C AF Espada, Jesus Varela, Ignacio Flores, Ignacio Ugalde, Alejandro P. Cadinanos, Juan Pendas, Alberto M. Stewart, Colin L. Tryggvason, Karl Blasco, Maria A. Freije, Jose M. P. Lopez-Otin, Carlos TI Nuclear envelope defects cause stem cell dysfunction in premature-aging mice SO JOURNAL OF CELL BIOLOGY LA English DT Article ID LABEL-RETAINING CELLS; BETA-CATENIN; PROGEROID SYNDROMES; MOUSE EPIDERMIS; LAMIN; HAIR; LAMINOPATHIES; ACTIVATION; EXPRESSION; DEFICIENT AB Nuclear lamina alterations occur in physiological aging and in premature aging syndromes. Because aging is also associated with abnormal stem cell homeostasis, we hypothesize that nuclear envelope alterations could have an important impact on stem cell compartments. To evaluate this hypothesis, we examined the number and functional competence of stem cells in Zmpste24-null progeroid mice, which exhibit nuclear lamina defects. We show that Zmpste24 deficiency causes an alteration in the number and proliferative capacity of epidermal stem cells. These changes are associated with an aberrant nuclear architecture of bulge cells and an increase in apoptosis of their supporting cells in the hair bulb region. These alterations are rescued in Zmpste24(-/-) Lmna(+/-) mutant mice, which do not manifest progeroid symptoms. We also report that molecular signaling pathways implicated in the regulation of stem cell behavior, such as Wnt and microphthalmia transcription factor, are altered in Zmpste24(-/-) mice. These findings establish a link between age-related nuclear envelope defects and stem cell dysfunction. C1 [Espada, Jesus; Varela, Ignacio; Ugalde, Alejandro P.; Cadinanos, Juan; Pendas, Alberto M.; Freije, Jose M. P.; Lopez-Otin, Carlos] Univ Oviedo, Inst Univ Oncol, Fac Med, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain. [Flores, Ignacio; Blasco, Maria A.] Spanish Natl Canc Res Ctr, Mol Oncol Program, Telomeres & Telomerase Grp, Madrid 28029, Spain. [Stewart, Colin L.] Natl Canc Inst, Ft Detrick, MD 21702 USA. [Tryggvason, Karl] Karolinska Inst, Dept Biophys & Biochem, Div Matrix Biol, SE-17177 Stockholm, Sweden. RP Lopez-Otin, C (reprint author), Univ Oviedo, Inst Univ Oncol, Fac Med, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain. EM clo@uniovi.es RI Freije, Jose M.P./A-6535-2008; Pendas, Alberto/L-1017-2014; Flores, Ignacio/E-8304-2016; Varela, Ignacio/G-1699-2016; Lopez-Otin, Carlos/C-6657-2013; Blasco , Maria A./M-1694-2014 OI Pendas, Alberto M/0000-0001-9264-3721; Freije, Jose M.P./0000-0002-4688-8266; Flores, Ignacio/0000-0001-8789-6396; Varela, Ignacio/0000-0002-0969-506X; Lopez-Otin, Carlos/0000-0001-6964-1904; Blasco , Maria A./0000-0002-4211-233X NR 36 TC 94 Z9 96 U1 0 U2 8 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 APR 7 PY 2008 VL 181 IS 1 BP 27 EP 35 DI 10.1083/jcb.200801096 PG 9 WC Cell Biology SC Cell Biology GA 284ZG UT WOS:000254746500005 PM 18378773 ER PT J AU Horkay, F Basser, PJ Hecht, AM Geissler, E AF Horkay, Ferenc Basser, Peter J. Hecht, Anne-Marie Geissler, Erik TI Gel-like behavior in aggrecan assemblies SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID ATOMIC-FORCE MICROSCOPY; CARTILAGE AGGRECAN; X-RAY; MACROMOLECULES; PROTEOGLYCANS; SCATTERING; NANOMECHANICS; AGGREGATE; POLYMER AB Aggrecan, a large biological polyelectrolyte molecule with a bottlebrush shape, forms complexes with hyaluronic acid (HA) that provide compressive resistance in cartilage. In solutions of aggrecan alone, the concentration dependence of the osmotic pressure Pi is marked by self-assembly of the molecules into aggregates. When HA is added to the solution at low aggrecan concentration c, the osmotic pressure is reduced, but in the physiological concentration range this trend is reversed. The osmotic modulus c partial derivative Pi/partial derivative c, which determines load bearing resistance, is enhanced in the HA-containing solutions. Dynamic light scattering (DLS) measurements show that the aggregates behave like microgels and that they become denser as the aggrecan concentration increases. The degree of densification is greatest at large distance scales in the microgels, but decreases at short distance scales. Measurements at higher resolution, involving small angle neutron scattering and small angle x-ray scattering (SAXS), confirm that at length scales shorter than 1000 angstrom, the density is independent of the concentration and that the individual bottlebrushes in the microgels retain their identity. The absence of collective diffusion modes in the relaxation spectrum, measured by DLS and neutron spin echo, corroborates the lack of interpenetration among the aggrecan subunits in the microgel. Complexation with HA modifies the long-range spatial organization of the microgels. Comparison of the scattering pattern of the individual aggrecan molecules obtained from SAXS measurements with that of the complexes measured by DLS shows that the aggrecan-HA structure is denser and is more uniform than the random microgels. This enhanced space-filling property allows higher packing densities to be attained, thus, optimizing resistance to osmotic compression. (c) 2008 American Institute of Physics. C1 [Horkay, Ferenc; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. [Hecht, Anne-Marie; Geissler, Erik] Univ Grenoble 1, Lab Spect Phys, CNRS, UMR 5588, F-38402 St Martin Dheres, France. RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, Natl Inst Hlth, 13 S Dr, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov RI Basser, Peter/H-5477-2011; d2am, beamline/I-6445-2015 FU Intramural NIH HHS NR 34 TC 18 Z9 18 U1 4 U2 29 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 APR 7 PY 2008 VL 128 IS 13 AR 135103 DI 10.1063/1.2884350 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 285LR UT WOS:000254778800064 PM 18397110 ER PT J AU Ben-Tal, A Smith, JC AF Ben-Tal, Alona Smith, Jeffrey C. TI A model for control of breathing in mammals: Coupling neural dynamics to peripheral gas exchange and transport SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE neural control; respiration; gas exchange; apnea ID RESPIRATORY RHYTHM GENERATION; PRE-BOTZINGER COMPLEX; VENTILATORY CONTROL-SYSTEM; PERSISTENT SODIUM CURRENT; PACEMAKER NEURONS; INTEGRATED MODEL; NETWORK; HYPERCAPNIA; MECHANISMS; HYPOXIA AB A new model for aspects of the control Of respiration in mammals has been developed. The model integrates a reduced representation of the brainstem respiratory neural controller together with peripheral gas exchange and transport mechanisms. The neural controller consists of two components. One component represents the inspiratory oscillator in the pre-Botzinger complex (pre-BotC) incorporating biophysical mechanisms for rhythm generation. The other component represents the ventral respiratory group (VRG), which is driven by the pre-BotC for generation of inspiratory (pre)motor output. The neural model was coupled to simplified models of the lungs incorporating oxygen and carbon dioxide transport. The simplified representation of the brainstem neural circuitry has regulation of both frequency and amplitude of respiration and is done in response to partial pressures of oxygen and carbon dioxide in the blood using proportional (P) and proportional plus integral (PI) controllers. We have studied the coupled system under open and closed loop control. We show that two breathing regimes can exist in the model. In one regime an increase in the inspiratory frequency is accompanied by an increase in amplitude. In the second regime an increase in frequency is accompanied by a decrease in amplitude. The dynamic response of the model to changes in the concentration of inspired 02 or inspired CO was compared qualitatively with experimental data reported in the physiological literature. We show that the dynamic response with a PI-controller fits the experimental data better but suggests that when high levels Of CO2 are inspired the respiratory system cannot reach steady state. Our model also predicts that there could be two possible mechanisms for apnea appearance when 100% O-2 is inspired following a period of 5% inspired O-2. This paper represents a novel attempt to link neural control and gas transport mechanisms, highlights important issues in amplitude and frequency control and sets the stage for more complete neurophysiological control models. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Ben-Tal, Alona] Massey Univ, Inst Informat & Math Sci, Auckland, New Zealand. [Smith, Jeffrey C.] NINDS, Cellular & Syst Neurobiol Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Ben-Tal, A (reprint author), Massey Univ, Inst Informat & Math Sci, Private Bag 102-904,N Shore Mail Ctr, Auckland, New Zealand. EM a.ben-tal@massey.ac.nz; jsmith@helix.nih.gov FU Intramural NIH HHS [Z01 NS002899-14] NR 48 TC 14 Z9 15 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD APR 7 PY 2008 VL 251 IS 3 BP 480 EP 497 DI 10.1016/j.jtbi.2007.12.018 PG 18 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 289VM UT WOS:000255082000008 PM 18262570 ER PT J AU Wright, MH Robles, AI Herschkowitz, JI Hollingshead, MG Anver, MR Perou, CM Varticovski, L AF Wright, Mollie H. Robles, Ana I. Herschkowitz, Jason I. Hollingshead, Melinda G. Anver, Miriam R. Perou, Charles M. Varticovski, Lyuba TI Molecular analysis reveals heterogeneity of mouse mammary tumors conditionally mutant for BrcaI SO MOLECULAR CANCER LA English DT Article ID BREAST-CANCER CELLS; GENETIC INSTABILITY; GLAND CELLS; DNA-DAMAGE; IDENTIFICATION; CARCINOMA; MODELS; MICE; CLASSIFICATION; POPULATION AB Background: Development of therapies for patients with BRCAI mutations has been hampered by lack of readily available in vitro and in vivo models. We recently showed that transplantation of transgenic mammary tumors as cell suspensions into naive recipients generates reproducible tumors with remarkable stability of gene expression profile. We examined the expression profiles of original and serially transplanted mammary tumors from BrcaI deficient mice, and tumor derived cell lines to validate their use for preclinical testing and studies of tumor biology. Methods: Original tumors, serially transplanted and multiple cell lines derived from BrcaI mammary tumors were characterized by morphology, gene and protein expression, and cell surface markers. Results: Gene expression among BrcaI tumors showed more heterogeneity than among previously characterized tumors from MMTV-PyMT and -WntI models. Gene expression data segregated BrcaI tumors into 3 distinct types: basal, mixed luminal, and tumors with epithelial-to-mesenchymal transition (EMT). Serial transplantation of individual tumors and multiple cell lines derived from the original tumors recapitulated the molecular characteristics of each tumor of origin. One tumor had distinct features of EMT and gave rise to cell lines that contained a distinct CD44(+)/CD24-/low population that may correlate with human breast cancer stem cells. Conclusion: Although individual tumors expanded by transplantation maintain the genomic profile of the original tumors, the heterogeneity among BrcaI tumors limits the extent of their use for preclinical testing. However, cell lines offer a robust material for understanding tumor biology and response to therapies driven by BRCAI deficiency. C1 [Wright, Mollie H.; Robles, Ana I.; Varticovski, Lyuba] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Anver, Miriam R.] NCI Frederick, FVC 301, SAIC Frederick Inc, Frederick, MD 21702 USA. [Herschkowitz, Jason I.; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Hollingshead, Melinda G.] FVC 205, Div Canc Treatment & Diag, Dev Therapeut Program, Frederick, MD 21701 USA. RP Varticovski, L (reprint author), NCI, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM molliewright@gmail.com; roblesa@mail.nih.gov; herschko@bcm.tmc.edu; hollingm@mail.nih.gov; manver@ncifcrf.gov; cperou@med.unc.edu; varticol@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [R01 CA101227, R01-CA-101227-01, P50-CA58223-09A1, P50 CA058223]; PHS HHS [N01-C0-12400] NR 38 TC 18 Z9 20 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD APR 7 PY 2008 VL 7 AR 29 DI 10.1186/1476-4598-7-29 PG 12 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 292QW UT WOS:000255282200001 PM 18394172 ER PT J AU Ambudkar, SV Kim, IW Cuenca, LL Nandigama, K Sauna, ZE AF Ambudkar, Suresh V. Kim, In-Wha Cuenca, Luciann L. Nandigama, Krishnamachary Sauna, Zuben E. TI MEDI 157-Mechanism of action of the multidrug resistance-linked P-glycoprotein (ABCB1) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Ambudkar, Suresh V.; Kim, In-Wha; Cuenca, Luciann L.; Nandigama, Krishnamachary; Sauna, Zuben E.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM ambudkar@mail.nih.gov; saunaz@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 157-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107102 ER PT J AU Andrei, D Maciag, A Chakrapani, H Citro, ML Saavedra, JE Keefer, LK AF Andrei, Daniela Maciag, Anna Chakrapani, Harinath Citro, Michael L. Saavedra, Joseph E. Keefer, Larry K. TI MEDI 341-Synthesis of bis-diazeniumdiolates and their in vitro activities toward cancer cell lines SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Andrei, Daniela; Chakrapani, Harinath; Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Maciag, Anna; Citro, Michael L.; Saavedra, Joseph E.] SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. EM saavj@mail.ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 341-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107189 ER PT J AU Appella, DH AF Appella, Daniel H. TI CARB 5-Functionalized polyamines with selective binding to TAR RNA SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 5-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775101120 ER PT J AU Bai, X Son, SJ Zhang, SX Liu, W Jordan, EK Frank, JA Venkatesan, T Lee, SB AF Bai, Xia Son, Sang Jun Zhang, Shixiong Liu, Wei Jordan, Elaine K. Frank, Joseph A. Venkatesan, Thirumalai Lee, Sang Bok TI INOR 498-In vitro cellular labeling of magnetic nanotubes for magnetic resonance imaging SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Bai, Xia; Son, Sang Jun; Lee, Sang Bok] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Zhang, Shixiong; Venkatesan, Thirumalai] Univ Maryland, Ctr Superconduct Res, College Pk, MD 20742 USA. [Liu, Wei] Philips Res N Amen, Clin Sites Res Program, Briarcliff Manor, NY 10510 USA. [Jordan, Elaine K.; Frank, Joseph A.] NIH, Lab Diagnost Radiol Res, Ctr Clin, Bethesda, MD 20892 USA. EM xbai@umd.edu; jafrank@helix.nih.gov; slee@umd.edu RI Venkatesan, Thirumalai/E-1667-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 498-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775106279 ER PT J AU Bai, X Son, SJ Liu, W Jordan, EK Frank, JA Zhang, S Venkatesan, T Nan, A Ghandehari, H Lee, SB AF Bai, Xia Son, Sang Jun Liu, Wei Jordan, Elaine K. Frank, Joseph A. Zhang, Shixiong Venkatesan, Thirumalai Nan, Anjan Ghandehari, Hamid Lee, Sang Bok TI COLL 240-Synthesis of magnetic nanotubes as magnetic resonance imaging contrast agents and in vitro cytotoxicity and cell labeling SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Bai, Xia; Son, Sang Jun; Lee, Sang Bok] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Liu, Wei] Philips Res N Amen, Clin Sites Res Program, Briarcliff Manor, NY 10510 USA. [Jordan, Elaine K.; Frank, Joseph A.] NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. [Zhang, Shixiong; Venkatesan, Thirumalai] Univ Maryland, Ctr Supercond Res, College Pk, MD 20742 USA. [Nan, Anjan; Ghandehari, Hamid] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Ctr Nanomed & Cellular Delivery, Baltimore, MD 21201 USA. EM xbai@umd.edu; jafrank@helix.nih.gov; hghandeh@rx.umaryland.edu; slee@umd.edu RI Venkatesan, Thirumalai/E-1667-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 240-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775103616 ER PT J AU Barry, CE Singh, R Ledwidge, R Ha, YH Lee, IY Manjunatha, U Boshoff, H AF Barry, Clifton E. Singh, Ramandeep Ledwidge, Richard Ha, Young Hwan Lee, Ill-Young Manjunatha, Ujjini Boshoff, Helena TI MEDI 328-The mechanism of bioreduction of nitroimidazooxanes by Mycobacterium tuberculosis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Barry, Clifton E.; Singh, Ramandeep; Ledwidge, Richard; Ha, Young Hwan; Lee, Ill-Young; Manjunatha, Ujjini; Boshoff, Helena] NIAID, Lab Clin Infect Dis, Rockville, MD 20852 USA. EM clifton_barry@nih.gov RI Barry, III, Clifton/H-3839-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 328-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107334 ER PT J AU Bryant, SD Dekeyser, J Omiecinski, C Marczak, E Lazarus, LH AF Bryant, Sharon D. Dekeyser, Josh Omiecinski, Curt Marczak, Ewa Lazarus, Lawrence H. TI CINF 63-Ligand based virtual screening identifies CAR nuclear receptor activators and active opioid receptor molecules SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Bryant, Sharon D.] NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. [Dekeyser, Josh; Omiecinski, Curt; Marczak, Ewa] Penn State Univ, Dept Vet Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. EM bryant2@niehs.nih.gov; lazarus@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 63-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775103334 ER PT J AU Clogston, JD Zheng, JW McNeil, SE Patri, AK AF Clogston, Jeffrey D. Zheng, Jiwen McNeil, Scott E. Patri, Anil K. TI Batch vs. flow mode DLS metrology: The effect on nanoparticles size SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Clogston, Jeffrey D.; Zheng, Jiwen; McNeil, Scott E.; Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Frederick, MD 21701 USA. EM clogstonj@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 457-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775109539 ER PT J AU Clogston, JD Zheng, JW Ramalinga, U McNeil, SE Patri, AK AF Clogston, Jeffrey D. Zheng, Jiwen Ramalinga, Uma McNeil, Scott E. Patri, Anil K. TI Physico-chemical characterization of nanomaterials for cancer diagnosis, imaging, and therapy SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Clogston, Jeffrey D.; Zheng, Jiwen; Ramalinga, Uma; McNeil, Scott E.; Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Frederick, MD 21701 USA. EM clogstonj@mail.nih.gov; mcneils@ncifcrf.gov NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 507-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775109537 ER PT J AU Collier, G Stuart, SJ Brooks, BR Latour, RA AF Collier, Galen Stuart, Steven J. Brooks, Bernard R. Latour, Robert A., Jr. TI COMP 191-Simulated interactions between structured peptides and functionalized surfaces SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Collier, Galen; Latour, Robert A., Jr.] Clemson Univ, Dept Bioengn, Clemson, SC 29634 USA. [Stuart, Steven J.] Clemson Univ, Dept Chem, Clemson, SC 29634 USA. [Brooks, Bernard R.] NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. EM gcollie@clemson.edu; ss@clemson.edu; brbrooks@helix.nih.gov; latourr@clemson.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 191-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775104206 ER PT J AU Costanzi, S AF Costanzi, Stefano TI COMP 116-On the applicability of GPCR homology modeling to drug discovery: A comparison between crystal structure and in silico model of the beta 2 adrenergic receptor complexed with carazolol SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM stefanoc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 116-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775104264 ER PT J AU Cotten, SW Pak, KD Stables, JP Kohn, H Liu, RH AF Cotten, Steven W. Pak, Ki Duk Stables, James P. Kohn, Harold Liu, Rihe TI BIOL 10-Click chemistry for identification of the targets of (R)-lacosamide SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Cotten, Steven W.; Pak, Ki Duk; Kohn, Harold; Liu, Rihe] Univ N Carolina, Div Med Chem & Nat Prod, Sch Pharm, Chapel Hill, NC 27599 USA. [Stables, James P.] NINDS, Epilepsy Branch, NIH, Rockville, MD 20852 USA. EM swcotten@email.unc.edu; rliu@email.unc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 10-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100668 ER PT J AU Coxon, B AF Coxon, Bruce TI CARB 103-The stereochemical dependence of 15N-1H NMR coupling constants in amino sugars SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Coxon, Bruce] NIH, Bethesda, MD 20892 USA. EM coxonb@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 103-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775101117 ER PT J AU Daly, JW AF Daly, John W. TI MEDI 194-Natural products as research probes: Impact on pharmacology, physiology and drug development SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Daly, John W.] NIDDK, Sect Pharmacodynam, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM jdaly@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 194-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107325 ER PT J AU Fang, ZL Cushman, M Hamel, E Agoston, GE AF Fang, Zhenglai Cushman, Mark Hamel, Ernest Agoston, Gregory E. TI MEDI 125-3,3-Diarylacrylonitriles as tubulin polymerization inhibitors for cancer chemotherapy SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Fang, Zhenglai; Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. [Cushman, Mark] Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. [Hamel, Ernest] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. [Agoston, Gregory E.] EntreMed Inc, Rockville, MD 20850 USA. EM fang@purdue.edu; cushman@pharmacy.purdue.edu; grega@entremed.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 125-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107004 ER PT J AU Filippov, IV Nicklaus, MC AF Filippov, Igor V. Nicklaus, Marc C. TI CINF 55-OSRA: Using open source optical structure recognition software to recover chemical information SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Filippov, Igor V.] NCI, Med Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Nicklaus, Marc C.] NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. EM igorf@helix.nih.gov; mn1@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 55-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775103235 ER PT J AU Ghosh, D Maynard, EL Berg, JM AF Ghosh, Debdip Maynard, Ernest L. Berg, Jeremy M. TI BIOL 25-Peroxisome biogenesis disorders: Peroxisomal targeting signal-1 binding to Pex5-C SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Ghosh, Debdip] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Maynard, Ernest L.] Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA. [Berg, Jeremy M.] NIGMS, Mol Biol Lab, Bethesda, MD 20892 USA. EM ghoshdeb@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 25-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100678 ER PT J AU Grimes, AF Lee, JC AF Grimes, Amy F. Lee, Jennifer C. TI PHYS 405-Xenon, laughing gas and cytochrome P450: Spectroscopic studies of inhaled anesthetics and their putative targets SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Grimes, Amy F.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. EM grimesa2@mail.nih.gov; leej4@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 405-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775109280 ER PT J AU Grimes, AF Lee, JC AF Grimes, Amy F. Lee, Jennifer C. TI INOR 629-Xenon, laughing gas and cytochrome P450: Spectroscopic studies of inhaled anesthetics and their putative targets SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Grimes, Amy F.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. EM gnimesa2@mail.nih.gov; leej4@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 629-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775106028 ER PT J AU Hassan, SA AF Hassan, Sergio A. TI COMP 111-Salt effects and explicit ions in continuum representations of water SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Hassan, Sergio A.] NIH, Ctr Mol Modeling, DHHS, Bethesda, MD 20892 USA. EM mago@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 111-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775104029 ER PT J AU Heredia-Moya, J Kirk, KL AF Heredia-Moya, Jorge Kirk, Kenneth L. TI MEDI 305-Synthesis of beta-methylthioaspartic acid and derivatives SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Heredia-Moya, Jorge; Kirk, Kenneth L.] NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM herediaj@niddk.nih.gov; kennethk@bdg8.niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 305-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107282 ER PT J AU Horkay, F Horkayne-Szakaly, I Lin, DC Dimitriadis, EK Silva, C Basser, PJ AF Horkay, Ferene Horkayne-Szakaly, Iren Lin, David C. Dimitriadis, Emilios K. Silva, Candida Basser, Peter J. TI BIOL 94-Physicochemical interactions between the major macromolecular components of cartilage matrix SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Horkay, Ferene; Horkayne-Szakaly, Iren; Lin, David C.; Silva, Candida; Basser, Peter J.] NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. [Dimitriadis, Emilios K.] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov; horkayi@mail.nih.gov; lindavid@mail.nih.gov; dimitria@helix.nih.gov; pjbasser@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 94-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100570 ER PT J AU Horkay, F Basser, PJ AF Horkay, Ferene Basser, Peter J. TI POLY 635-Ion-driven volume transitions in DNA gels SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA C1 [Horkay, Ferene; Basser, Peter J.] NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov; pjbasser@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 635-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519XJ UT WOS:000271802800296 ER PT J AU Hughes, JT AF Hughes, Joseph T., Jr. TI CHAS 13-Avenues for worker involvement in hazard assessment SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Hughes, Joseph T., Jr.] NIEHS, Worker Educ & Training Program, DHHS, NIH, Durham, NC 27709 USA. EM hughes3@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 13-CHAS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775101485 ER PT J AU Hummer, G Buchete, NV Best, RB Zheng, WJ Chen, YG Kim, YC AF Hummer, Gerhard Buchete, Nicolae-Viorel Best, Robert B. Zheng, Wenjun Chen, Yng-Gwei Kim, Young C. TI PHYS 135-Spatial and temporal coarse-graining in simulations of protein dynamics and complex formation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Hummer, Gerhard; Buchete, Nicolae-Viorel; Chen, Yng-Gwei; Kim, Young C.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. [Zheng, Wenjun] SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA. EM Gerhard.Hummer@nih.gov; buchete@nih.gov; rbb24@cam.ac.uk RI Hummer, Gerhard/A-2546-2013; Best, Robert/H-7588-2016 OI Hummer, Gerhard/0000-0001-7768-746X; Best, Robert/0000-0002-7893-3543 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 135-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775109335 ER PT J AU Ivanov, AA Jacobson, KA AF Ivanov, Andrei A. Jacobson, Kenneth A. TI COMP 184-Quantitative structure-activity relationship modeling of the A(2B) adenosine receptor agonists SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc, Div Cellulose & Renewble Mat C1 [Ivanov, Andrei A.; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. EM ivanovan@niddk.nih.gov; kajacobs@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 184-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775104045 ER PT J AU Kelly, RA Amann, BT Berg, JM AF Kelly, Rebekah A. Amann, Barbara T. Berg, Jeremy M. TI INOR 717-Metal binding studies of the c-terminal zinc binding domain of the NF-kappa B essential modulator (NEMO) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Kelly, Rebekah A.; Amann, Barbara T.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Berg, Jeremy M.] NIGMS, NIH, Bethesda, MD 20892 USA. EM kellyre@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 717-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775105814 ER PT J AU Kelly, RA Amann, BT Berg, JM AF Kelly, Rebekah A. Amann, Barbara T. Berg, Jeremy M. TI PRES 25-Metal binding studies of the c-terminal zinc binding domain of the NF-kappa B essential modulator SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA C1 [Kelly, Rebekah A.; Amann, Barbara T.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Berg, Jeremy M.] Natl Inst Gen Med Sci, NIH, Bethesda, MD 20892 USA. EM kellyre@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 25-PRES PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519XJ UT WOS:000271802801011 ER PT J AU Knudtson, CA Zhou, AH Shah, H VanderVelde, P Hanson, PR AF Knudtson, Christopher A. Zhou, Aihua Shah, Hetal VanderVelde, Paul Hanson, Paul R. TI ORGN 73-Oxa-Michael and Baylis-Hillman strategies toward synthesis of sultam libraries SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Knudtson, Christopher A.; Zhou, Aihua; Shah, Hetal; Hanson, Paul R.] Univ Kansas, Dept Chem, NIH, Ctr Excellence Chem Methodol & Lib Dev KU CMLD, Lawrence, KS 66045 USA. [VanderVelde, Paul] Hope Coll, Dept Chem, Holland, MI 49422 USA. EM snocrash@ku.edu; paul.vandervelde@hope.edu; phanson@ku.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 73-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775108434 ER PT J AU Li, Z Rogers, L Venable, R Murray, D Pastor, RW AF Li, Zheng Rogers, Laura Venable, Richard Murray, Diana Pastor, Richard W. TI PHYS 361-Simulations of bilayers containing phosphoinositides, important signaling lipids SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Li, Zheng; Rogers, Laura; Murray, Diana] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. [Venable, Richard; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. EM zl2169@columbia.edu; dm527@columbia.edu; pastorr@nhlbi.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 361-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775109334 ER PT J AU Liao, CZ Nicklaus, MC AF Liao, Chenzhong Nicklaus, Marc C. TI MEDI 6-Models of HIV-1 integrase/DNA complex SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Liao, Chenzhong; Nicklaus, Marc C.] NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. EM czliao@helix.nih.gov; mn1@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 6-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107212 ER PT J AU Liao, CZ Nicklaus, MC AF Liao, Chenzhong Nicklaus, Marc C. TI MEDI 248-Modeling of HIV integrase-DNA active site with two magnesium ions SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Liao, Chenzhong; Nicklaus, Marc C.] NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. EM czliao@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 248-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107167 ER PT J AU Long, TR Rayabarapu, DK Jimenez, M Wewel, J Klimberg, S Hanson, PR Flynn, DL AF Long, Toby R. Rayabarapu, Dinesh K. Jimenez, Maria Wewel, Josh Klimberg, Sarra Hanson, Paul R. Flynn, Daniel L. TI ORGN 74-ROMP strategies in library development SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Long, Toby R.; Rayabarapu, Dinesh K.; Jimenez, Maria; Hanson, Paul R.] Univ Kansas, Dept Chem, NIH, Ctr Excellence Chem Methodol & Lib Dev KU CMLD, Lawrence, KS 66045 USA. [Wewel, Josh; Klimberg, Sarra; Flynn, Daniel L.] Deciphera Pharmaceut LLC, Lawrence, KS 66047 USA. EM tbylong@ku.edu; phanson@ku.edu; dflynn@deciphera.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 74-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775108435 ER PT J AU Malhotra, SV Kumar, V Tomar, S Pei, C Parmar, VS AF Malhotra, Sanjay V. Kumar, Vineet Tomar, Shilpi Pei, Cao Parmar, Virinder S. TI ORGN 481-Application of ionic liquids in the synthesis of coumarin derivatives with anticancer activity SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Malhotra, Sanjay V.; Kumar, Vineet] NCI, Lab Synth Chem, SAIC Frederick, Frederick, MD 21702 USA. [Tomar, Shilpi; Pei, Cao; Parmar, Virinder S.] Univ Delhi, Dept Chem, Delhi 110007, India. EM malhotrasa@mail.nih.gov; kumarvin@mail.nih.gov; virparmar@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 481-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775108266 ER PT J AU Malhotra, SV Kumar, V Manin, N Alvez, G Tanielyan, SK Augustine, RL AF Malhotra, Sanjay V. Kumar, Vineet Manin, Norman Alvez, Gabriela Tanielyan, Setrak K. Augustine, Robert L. TI ORGN 482-Synthesis of nucleoside-based antiviral drugs in ionic liquids SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Malhotra, Sanjay V.; Kumar, Vineet] SAIC Frederick, Lab Synthet Chem, NCI, Frederick, MD 21702 USA. [Manin, Norman; Alvez, Gabriela; Tanielyan, Setrak K.; Augustine, Robert L.] Seton Hall Univ, Dept Chem & Biochem, Ctr Appl Catalysis, S Orange, NJ 07079 USA. EM malhotrasa@mail.nih.gov; kumarvin@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 482-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775108256 ER PT J AU Manzoni, MR Boeggeman, E Ramakrishnan, B Pasek, M Qasba, PK AF Manzoni, Maria R. Boeggeman, Elizabeth Ramakrishnan, Boopathy Pasek, Marta Qasba, Pradman Krishen TI ORGN 275-New synthetic sugar-nucleotide donor substrates for glycosyltransferases SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Boeggeman, Elizabeth; Ramakrishnan, Boopathy] NCI, Struct Glycobiol Sect, Nanobiol Program, Ctr Canc Res,SAIC Inc,NIH, Frederick, MD 21702 USA. EM mmanzoni@ncifcrf.gov; eeb@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 275-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775108218 ER PT J AU Metaferia, BB Song, Y Khan, J AF Metaferia, Belhu B. Song, Young Khan, Javed TI MEDI 279-Synthesis and biological evaluations of peptide nucleic acids as siRNA mimics SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Metaferia, Belhu B.; Song, Young; Khan, Javed] NCI, Pediat Oncol Branch, Oncogenom Sect, Gaithersburg, MD 20877 USA. EM belhum@mail.nih.gov; songyo@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 279-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107294 ER PT J AU Miller, DS Hartz, AM Bauer, B AF Miller, David S. Hartz, Anika Ms. Bauer, Bjoern TI MEDI 159-Signals that modulate p-glycoprotein at the blood-brain barrier: Potential therapeutic targets SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Miller, David S.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Hartz, Anika Ms.] Univ Minnesota, Sch Med, Duluth, MN 55812 USA. [Bauer, Bjoern] Univ Minnesota, Coll Pharm, Duluth, MN 55812 USA. EM miller@niehs.nih.gov; amhartz@d.umn.edu; bjbauer@d.umn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 159-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107162 ER PT J AU Paul, NM Floresca, CZ Taylor, M Luedtke, RR Deschamps, JR Newman, AH AF Paul, Noel M. Floresca, Christina Z. Taylor, Michelle Luedtke, Robert R. Deschamps, Jeffrey R. Newman, Amy H. TI MEDI 48-Tuning affinity on a tropane framework for dopamine D2/D3 receptor subtype ligands SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Paul, Noel M.; Newman, Amy H.] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, Baltimore, MD 21224 USA. [Floresca, Christina Z.; Taylor, Michelle; Luedtke, Robert R.] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. [Deschamps, Jeffrey R.] USN, Res Lab, Washington, DC 20375 USA. EM pauln@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 48-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107013 ER PT J AU Pfefferkorn, CM Lee, JC AF Pfefferkorn, Candace M. Lee, Jennifer C. TI PHYS 336-Probing phospholipid induced -synuclein aggregation with tryptophan fluorescence SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Pfefferkorn, Candace M.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. EM pfefferc@mail.nih.gov; leej4@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 336-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775109271 ER PT J AU Pfefferkorn, CM Lee, JC AF Pfefferkorn, Candace M. Lee, Jennifer C. TI BIOL 31-Probing phospholipid induced alpha-synuclein aggregation with tryptophan fluorescence SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Pfefferkorn, Candace M.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. EM pfefferc@mail.nih.gov; leej4@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 31-BIOL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100620 ER PT J AU Pooput, C Pellett, P Heredia-Moya, J Kirk, KL AF Pooput, Chaya Pellett, Patrina Heredia-Moya, Jorge Kirk, Kenneth L. TI MEDI 273-Synthesis of ring fluorinated capsaicin analogs and their interactions with the vallinoid receptor SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Pooput, Chaya; Pellett, Patrina; Heredia-Moya, Jorge; Kirk, Kenneth L.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM pooputc@niddk.nih.gov; herediaj@niddk.nih.gov; kennethk@bdg8.niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 273-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107296 ER PT J AU Pooput, C Rosemond, E Costanzi, S Deflorian, F Kirk, KL Wess, J AF Pooput, Chaya Rosemond, Erica Costanzi, Stefano Deflorian, Francesca Kirk, Kenneth L. Wess, Juergen TI MEDI 126-Molecular basis of the selectivity of fluorinated neurotransmitters for adrenergic receptors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Pooput, Chaya; Rosemond, Erica; Kirk, Kenneth L.; Wess, Juergen] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. [Deflorian, Francesca] NIDDK, Computat Chem Core Lab, NIH, Bethesda, MD 20892 USA. EM pooputc@niddk.nih.gov; rosemonde@niddk.nih.gov; stefanoc@mail.nih.gov; deflorianf@niddk.nih.gov; kennethk@bdg8.niddk.nih.gov; jwess@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 126-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107223 ER PT J AU Poroikov, VV Filimonov, D Nicklaus, MC AF Poroikov, Vladimir V. Filimonov, Dmitry Nicklaus, Marc C. TI CINF 58-NIH Roadmap data: New possibilities for computer-aided drug discovery SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Poroikov, Vladimir V.; Filimonov, Dmitry] Russian Acad Med Sci, Inst Biomed Chem, Moscow 119121, Russia. [Nicklaus, Marc C.] NCI, Ctr Canc Res, NIH, Med Chem Lab, Frederick, MD 21702 USA. EM vladimir.poroikov@ibmc.msk.ru; dmitry.filimonov@ibmc.msk.ru; mn1@helix.nih.gov RI Poroikov, Vladimir/O-2769-2013 OI Poroikov, Vladimir/0000-0001-7937-2621 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 58-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775103310 ER PT J AU Ravindran, S Zharikova, O Nanovskaya, T Hill, R Mattison, D Hankins, G Ahmed, M AF Ravindran, Selvan Zharikova, Olga Nanovskaya, Tatiana Hill, Ronald Mattison, Donald Hankins, Gary Ahmed, Mahmoud TI MEDI 132-Investigation of glyburide and its metabolites in urine and plasma of pregnant patients under treatment for gestational diabetes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Ravindran, Selvan; Zharikova, Olga; Nanovskaya, Tatiana; Hankins, Gary; Ahmed, Mahmoud] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77550 USA. [Hill, Ronald] Univ Louisiana Monroe, Dept Basic Pharmaceut Sci, Coll Pharm, Monroe, LA USA. [Mattison, Donald] NICHD, Ctr Res Mother & Children, Obstet Fetal Pharmacol Res Units OPRU Network, Bethesda, MD USA. EM seravind@utmb.edu RI Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 132-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775107284 ER PT J AU Rayabarapu, DK Hanson, PR AF Rayabarapu, Dinesh K. Hanson, Paul R. TI ORGN 71-Metathesis and Heck strategies to bi- and tricyclic sultam libraries SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Rayabarapu, Dinesh K.; Hanson, Paul R.] Univ Kansas, Dept Chem, NIH, Ctr Excellence Chem Methodol & Lib Dev KU CMLD, Lawrence, KS 66045 USA. EM drdinesh@ku.edu; phanson@ku.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 71-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775108433 ER PT J AU Santacroce, PV Pozsgay, V AF Santacroce, Paul V. Pozsgay, Vince TI CARB 112-Oxidation of carbohydrates using dimethyl sulfoxide and the pyridine-sulfur trioxide complex reagent SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Santacroce, Paul V.; Pozsgay, Vince] NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. EM psantacr@mail.nih.gov; pozsgayv@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 112-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775101037 ER PT J AU Scanlon, KA Traum, KE Krall, SE Wilson, D Johnstone, K AF Scanlon, Kelly A. Traum, Kerstin E. Krall, Suzanne E. Wilson, Deborah Johnstone, Karyn TI CHAS 3-STAR-LITE: An innovative approach to delivering laboratory safety training to students SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Scanlon, Kelly A.; Traum, Kerstin E.; Krall, Suzanne E.; Wilson, Deborah; Johnstone, Karyn] NIH, Div Occupat Hlth & Safety, Bethesda, MD 20892 USA. EM scanlonk@mail.nih.gov; traumker@mail.nih.gov; kralls@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 3-CHAS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775101491 ER PT J AU Sitzmann, M Filippov, IV Ihlenfeldt, WD Nicklaus, MC AF Sitzmann, Markus Filippov, Igor V. Ihlenfeldt, Wolf-Dietrich Nicklaus, Marc C. TI CINF 91-Chemical Structure Lookup Service (CSLS) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Sitzmann, Markus; Nicklaus, Marc C.] NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. [Filippov, Igor V.] NCI, Med Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Ihlenfeldt, Wolf-Dietrich] Xemistry GmbH, D-35094 Lahntal, Germany. EM sitzmann@helix.nih.gov; igorf@helix.nih.gov; mn1@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 91-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775103277 ER PT J AU Steinbach, PJ AF Steinbach, Peter J. TI COMP 172-Iterative refinement of parameters for computer simulation of peptides and proteins SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Steinbach, Peter J.] Natl Inst Hlth, Ctr Mol Modeling, CIT, Bethesda, MD 20892 USA. EM steinbac@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 172-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775104117 ER PT J AU Tang, H Wang, XS Huang, XP Roth, BL Kozikowski, AP Tropsha, A AF Tang, Hao Wang, Xiang S. Huang, Xi-Ping Roth, Bryan L. Kozikowski, Alan P. Tropsha, Alexander TI COMP 140-Combinatorial QSAR analysis of histone deacetylase inhibitors and QSAR-based virtual screening SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Tang, Hao; Wang, Xiang S.; Tropsha, Alexander] Univ N Carolina, Sch Pharm, Lab Mol Modeling, Chapel Hill, NC 27599 USA. [Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. [Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Kozikowski, Alan P.] Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. EM tangh@email.unc.edu; xswang@email.unc.edu; bryan_roth@med.unc.edu; alex_tropsha@unc.edu RI Roth, Bryan/F-3928-2010; Tropsha, Alexander/G-6245-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 140-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775104157 ER PT J AU Upton, TG Osuna, J Kashemirov, BA McKenna, CE Goodman, MF Sucato, CA Wilson, SH Batra, VK Pedersen, LC Beard, WA AF Upton, Thomas G. Osuna, Jorge Kashemirov, Boris A. McKenna, Charles E. Goodman, Myron F. Sucato, Christopher A. Wilson, Samuel H. Batra, Vinod K. Pedersen, Lars C. Beard, William A. TI ORGN 278-Synthesis and pKa values of stereoelectronically diverse methylenebisphosphonic acids: A nucleotide analog toolkit to probe nucleic acid polymerase structure and function SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Upton, Thomas G.; Osuna, Jorge; Kashemirov, Boris A.; McKenna, Charles E.; Goodman, Myron F.; Sucato, Christopher A.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. [Goodman, Myron F.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. [Wilson, Samuel H.; Batra, Vinod K.; Pedersen, Lars C.; Beard, William A.] Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM tupton@usc.edu; mgoodman@usc.edu; csucato@usc.edu; wilson5@niehs.nih.gov RI Upton, Thomas/E-3749-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 278-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775108103 ER PT J AU Vellore, NA Brooks, BR Bruce, DA Stuart, SJ Latour, RA AF Vellore, N. A. Brooks, B. R. Bruce, D. A. Stuart, S. J. Latour, R. A. TI COMP 255-Calculation of adsorption free energy for peptide-surface interactions using biased-REMD simulations SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Vellore, N. A.; Latour, R. A.] Clemson Univ, Dept Bioengn, Clemson, SC 29634 USA. [Brooks, B. R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Bruce, D. A.] Clemson Univ, Dept Chem & Biomol Engn, Clemson, SC 29634 USA. [Stuart, S. J.] Clemson Univ, Dept Chem, Clemson, SC 29681 USA. EM nvellor@clemson.edu; brb@nih.gov; dbruce@clemson.edu; ss@clemson.edu; latourr@clemson.edu RI Bruce, David/E-9572-2011; Vellore, Nadeem/C-5763-2011 OI Vellore, Nadeem/0000-0003-4853-1508 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 255-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775104184 ER PT J AU Vu, VV Emerson, JP Martinho, M Kim, YS Munck, E Park, MH Que, L AF Vu, Van V. Emerson, Joseph P. Martinho, Marlene Kim, Yeon Sook Munck, Eckard Park, Myung Hee Que, Lawrence, Jr. TI INOR 200-Human deoxyhypusine hydroxylase is a diiron enzyme SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Vu, Van V.; Emerson, Joseph P.; Que, Lawrence, Jr.] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. [Martinho, Marlene; Munck, Eckard] Carnegie Mellon Univ, Dept Chem, Pittsburgh, PA 15213 USA. [Kim, Yeon Sook; Park, Myung Hee] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [Que, Lawrence, Jr.] Univ Minnesota, Ctr Met Blocatalysis, Minneapolis, MN 55455 USA. EM vanvu@chem.umn.edu; mmartinh@andrew.cmu.edu; emunck@cmu.edu; mpark@dir.nidcr.nih.gov; que@chem.umn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 200-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775105643 ER PT J AU Weidlich, IE Tarasov, SG Filippov, IV Nicklaus, MC AF Weidlich, Iwona E. Tarasov, Sergey G. Filippov, Igor V. Nicklaus, Marc C. TI COMP 242-Examination of proposed intercalation models for imidazoacridone related compounds SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Weidlich, Iwona E.; Nicklaus, Marc C.] NCI, Ctr Canc Res, NIH, DHHS,Lab Med Chem, Frederick, MD 21702 USA. [Tarasov, Sergey G.] NCI, Struct Biophys Lab, Frederick, MD 21702 USA. [Filippov, Igor V.] NCI, Med Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. EM iweidlic@helix.nih.gov; tarasovs@ncifcrf.gov; igorf@helix.nih.gov; mn1@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 242-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775104046 ER PT J AU Zhong, MH Liao, CZ Melman, A Jacobson, KA Marquez, VE AF Zhong, Minghong Liao, Chenzhong Melman, Artem Jacobson, Kenneth A. Marquez, Victor E. TI ORGN 690-Synthesis of south locked bicyclo[3.1.0]hexane ribonucleosides to study the effect of sugar pucker on RNA cleavage SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Liao, Chenzhong] NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. [Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Marquez, Victor E.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. EM minghong@mail.nih.gov; czliao@helix.nih.gov; melmana@mail.nih.gov; marquezv@dc37a.nci.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 690-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775108167 ER PT J AU Qiao, LP Zou, CH Shao, P Schaack, J Johnson, PF Shao, JH AF Qiao, Liping Zou, Chenhui Shao, Peng Schaack, Jerome Johnson, Peter F. Shao, Jianhua TI Transcriptional regulation of fatty acid Translocase/CD36 expression by CCAAT/Enhancer-binding protein alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADIPONECTIN GENE-EXPRESSION; SKELETAL-MUSCLE; C/EBP-BETA; SARCOLEMMAL FAT/CD36; ADIPOSE-TISSUE; NULL MUTATION; CD36; TRANSPORT; INSULIN; GLUCOSE AB Fatty acid translocase (FAT/CD36) plays an important role in facilitating long chain fatty acid transport. FAT/CD36 gene deletion protects mice from high fat diet-induced obesity. In this study we have investigated the regulatory mechanism of FAT/CD36 expression at the transcription level. FAT/CD36 expression was activated during 3T3-L1 adipocyte differentiation, and FAT/CD36 protein levels were positively correlated with CCAAT/enhancer-binding protein alpha(C/EBP alpha) and peroxisome proliferator-activated receptor gamma. However, a negative correlation was detected between FAT/CD36 and C/EBP ss. Overexpression of C/EBP alpha or C/EBP ss increased FAT/CD36 mRNAand protein levels in several types of cells. Restoration of C/EBP alpha or C/EBP ss expression in C/EBP alpha- or C/EBP ss-deficient mouse embryonic fibroblasts increased FAT/CD36 expression. However, in mouse embryonic fibroblasts C/EBP alpha was a more potent activator of FAT/CD36 expression than was C/EBP alpha. Expression of C/EBP ss robustly increased FAT/CD36 proximal promoter- directed luciferase expression in human embryonic kidney 293 cells. A C/EBP-responsive element was identified in the FAT/CD36 promoter by using 5 ' and specific site mutations. The binding of C/EBP alpha in the FAT/CD36 promoter was detected by chromatin immunoprecipitation in 3T3-L1 adipocytes. These results demonstrated that C/EBP alpha regulates FAT/CD36 gene expression at the transcriptional level. C1 [Qiao, Liping; Zou, Chenhui; Shao, Peng; Shao, Jianhua] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY 40536 USA. [Schaack, Jerome] Univ Colorado Denver, Dept Microbiol, Aurora, CO 80045 USA. [Schaack, Jerome] Hlth Sci Ctr, Aurora, CO 80045 USA. [Johnson, Peter F.] NCI Frederick, Natl Inst Hlth, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RP Shao, JH (reprint author), Univ Kentucky, Grad Ctr Nutr Sci, 900 S Limestone, Lexington, KY 40536 USA. EM JianhuaShao@uky.edu RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU Intramural NIH HHS; NIDDK NIH HHS [R DK 077643 A] NR 37 TC 23 Z9 24 U1 1 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 APR 4 PY 2008 VL 283 IS 14 BP 8788 EP 8795 DI 10.1074/jbc.M800055200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 280ZO UT WOS:000254465800004 PM 18263877 ER PT J AU Mochizuki, K Nishiyama, A Jang, MK Dey, A Ghosh, A Tamura, T Natsume, H Yao, HJ Ozato, K AF Mochizuki, Kazuki Nishiyama, Akira Jang, Moon Kyoo Dey, Anup Ghosh, Anu Tamura, Tomohiko Natsume, Hiroko Yao, Hongjie Ozato, Keiko TI The bromodomain protein Brd4 stimulates G(1) gene transcription and promotes progression to S phase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-II; PAPILLOMAVIRUS E2 PROTEIN; CELL-CYCLE PROGRESSION; NF-KAPPA-B; P-TEFB; SUBCELLULAR-LOCALIZATION; ACETYLATED CHROMATIN; MITOTIC CHROMOSOMES; DNA-REPLICATION; CDNA MICROARRAY AB Brd4 is a bromodomain protein that binds to acetylated chromatin. It regulates cell growth, although the underlying mechanism has remained elusive. Brd4 has also been shown to control transcription of viral genes, whereas its role in transcription of cellular genes has not been fully elucidated. Here we addressed the role of Brd4 in cell growth and transcription using a small hairpin ( sh) RNA approach. The Brd4 shRNA vector stably knocked down Brd4 protein expression by similar to 90% in NIH3T3 cells and mouse embryonic fibroblasts. Brd4 knockdown cells were growth impaired and grew more slowly than control cells. When synchronized by serum starvation and released, Brd4 knockdown cells were arrested at G(1), whereas control cells progressed to S phase. In microarray analysis, although numerous genes were up-regulated during G(1) in control cells, many of these G(1) genes were not up-regulated in Brd4 knockdown cells. Reintroduction of Brd4 rescued expression of these G(1) genes in Brd4 knockdown cells, allowing cells to progress toward S phase. Chromatin immunoprecipitation analysis showed that Brd4 was recruited to the promoters of these G(1) genes during G(0)-G(1) progression. Furthermore, Brd4 recruitment coincided with increased binding of Cdk9, a component of P-TEFb and RNA polymerase II to these genes. Brd4 recruitment was low to absent at genes not affected by Brd4 shRNA. The results indicate that Brd4 stimulates G(1) gene expression by binding to multiple G(1) gene promoters in a cell cycle-dependent manner. C1 [Mochizuki, Kazuki; Nishiyama, Akira; Jang, Moon Kyoo; Dey, Anup; Ghosh, Anu; Tamura, Tomohiko; Natsume, Hiroko; Yao, Hongjie; Ozato, Keiko] NICHD, NIH, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. RP Ozato, K (reprint author), NICHD, NIH, Lab Mol Growth Regulat, Bldg 6,Rm 2A01,6 Ctr Dr, Bethesda, MD 20892 USA. EM ozatok@nih.go FU Intramural NIH HHS NR 44 TC 103 Z9 104 U1 0 U2 7 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 APR 4 PY 2008 VL 283 IS 14 BP 9040 EP 9048 DI 10.1074/jbc.M707603200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 280ZO UT WOS:000254465800034 PM 18223296 ER PT J AU Kim, K Choi, J Heo, K Kim, H Levens, D Kohno, K Johnson, EM Brock, HW An, W AF Kim, Kyunghwan Choi, Jongkyu Heo, Kyu Kim, Hyunjung Levens, David Kohno, Kimitoshi Johnson, Edward M. Brock, Hugh W. An, Woojin TI Isolation and characterization of a novel H1.2 complex that acts as a repressor of p53-mediated transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LINKER HISTONE FUNCTION; GENE-EXPRESSION; IN-VIVO; PUR-ALPHA; CHROMATIN-STRUCTURE; DNA-BINDING; POLY(ADP-RIBOSE) POLYMERASE; NUCLEOSOME; PROTEIN; P53 AB Linker histone H1 has been generally viewed as a global repressor of transcription by preventing the access of transcription factors to sites in chromatin. However, recent studies suggest that H1 can interact with other regulatory factors for its action as a negative modulator of specific genes. To investigate these aspects, we established a human cell line expressing H1.2, one of the H1 subtypes, for the purification of H1-interacting proteins. Our results showed that H1.2 can stably associate with sets of cofactors and ribosomal proteins that can significantly repress p53-dependent, p300-mediated chromatin transcription. This repressive action of H1.2 complex involves direct interaction of H1.2 with p53, which in turn blocks p300-mediated acetylation of chromatin. YB1 and PUR alpha, two factors present in the H1.2 complex, together with H1.2 can closely recapitulate the repressive action of the entire H1.2 complex in transcription. Chromatin immunoprecipitation and RNA interference analyses further confirmed that the recruitment of YB1, PUR alpha, and H1.2 to the p53 target gene Bax is required for repression of p53-induced transcription. Therefore, these results reveal a previously unrecognized function of H1 as a transcriptional repressor as well as the underlying mechanism involving specific sets of factors in this repression process. C1 [Kim, Kyunghwan; Choi, Jongkyu; Heo, Kyu; Kim, Hyunjung; An, Woojin] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. [Levens, David] NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA. [Kohno, Kimitoshi] Univ Occupat & Environm Hlth, Dept Mol Biol, Fukuoka 8078555, Japan. [Johnson, Edward M.] Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23501 USA. [Brock, Hugh W.] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z3, Canada. RP An, W (reprint author), Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. EM woojinan@usc.edu RI Levens, David/C-9216-2009; OI Levens, David/0000-0002-7616-922X; Heo, Kyu/0000-0001-8833-4731 NR 60 TC 60 Z9 63 U1 2 U2 5 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 APR 4 PY 2008 VL 283 IS 14 BP 9113 EP 9126 DI 10.1074/jbc.M708205200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 280ZO UT WOS:000254465800041 PM 18258596 ER PT J AU Gao, L Hanson, MN Balakrishnan, M Boyer, PL Roques, BP Hughes, SH Kim, B Bambara, RA AF Gao, Lu Hanson, Mark Nils Balakrishnan, Mini Boyer, Paul L. Roques, Bernard P. Hughes, Stephen H. Kim, Baek Bambara, Robert A. TI Apparent defects in processive DNA synthesis, strand transfer, and primer elongation of met-184 mutants of HIV-1 reverse transcriptase derive solely from a dNTP utilization defect SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; HIGH-LEVEL RESISTANCE; IN-VITRO; RNASE-H; GENETIC-RECOMBINATION; STERIC HINDRANCE; DRUG-RESISTANCE; 3TC RESISTANCE; WILD-TYPE AB The 2', 3'-dideoxy-3'-thiacytidine drug-resistant M184I HIV-1 reverse transcriptase (RT) has been shown to synthesize DNA with decreased processivity compared with the wild-type RT. M184A displays an even more severe processivity defect. However, the basis of this decreased processivity has been unclear, and both primer-template binding and dNTP interaction defects have been proposed to account for it. In this study, we show that the altered properties of the M184I and M184A RT mutants that we have measured, including decreased processivity, a slower rate of primer extension, and increased strand transfer activity, can all be explained by a defect in dNTP utilization. These alterations are observed only at low dNTP concentration and vanish as the dNTP concentration is raised. The mutant RTs exhibit a normal dissociation rate from a DNA primer-RNA template while paused during synthesis. Slower than normal synthesis at physiological dNTP concentration, coupled with normal dissociation from the primer-template, results in the lowered processivity. The mutant RTs exhibit normal DNA 3'-end-directed and RNA 5'-end-directed ribonuclease H activity. The reduced rate of DNA synthesis causes an increase in the ratio of ribonuclease H to polymerase activity thereby promoting increased strand transfer. These latter results are consistent with an observed higher rate of recombination by HIV-1 strains with Met-184 mutations. C1 [Gao, Lu; Hanson, Mark Nils; Balakrishnan, Mini; Bambara, Robert A.] Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA. [Kim, Baek] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA. [Boyer, Paul L.; Hughes, Stephen H.] NCI, NIH, HIV Drug Resistance Program, Frederick, MD 21702 USA. Univ Paris 05, CNRS, UFR Sci Pharmaceut & Biol,UMR 8600, Unite Pharmacochim Mol & Struct,INSERM U266, F-75270 Paris 06, France. RP Bambara, RA (reprint author), Univ Rochester, Med Ctr, Dept Biochem & Biophys, Box 712,601 Elmwood Ave, Rochester, NY 14642 USA. EM Robert_Bambara@urmc.rochester.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM 49573] NR 40 TC 23 Z9 23 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 APR 4 PY 2008 VL 283 IS 14 BP 9196 EP 9205 DI 10.1074/jbc.M710148200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 280ZO UT WOS:000254465800049 PM 18218634 ER PT J AU Patel, VN Likar, KM Zisman-Rozen, S Cowherd, SN Lassiter, KS Sher, I Yates, EA Turnbull, JE Ron, D Hoffman, MP AF Patel, Vaishali N. Likar, Karen M. Zisman-Rozen, Simona Cowherd, Samuel N. Lassiter, Keyonica S. Sher, Ifat Yates, Edwin A. Turnbull, Jeremy E. Ron, Dina Hoffman, Matthew P. TI Specific heparan sulfate structures modulate FGF10-mediated submandibular gland epithelial morphogenesis and differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; BRANCHING MORPHOGENESIS; SALIVARY-GLAND; RECEPTOR SPECIFICITY; CRYSTAL-STRUCTURE; FACTOR FAMILY; FGF; BINDING; MOUSE; EXPRESSION AB FGF10, a heparan sulfate ( HS)-binding growth factor, is required for branching morphogenesis of mouse submandibular glands ( SMGs). HS increases the affinity of FGF10 for FGFR2b, which forms an FGF10 center dot FGFR2b center dot HS ternary signaling complex, and results in diverse biological outcomes, including proliferation and epithelial morphogenesis. Defining the HS structures involved in specific FGF10-mediated events is critical to understand how HS modulates growth factor signaling in specific developmental contexts. We used HS-deficient BaF3/FGFR2b cells, which require exogenous HS to proliferate, to investigate the HS requirements for FGF10-mediated proliferation and primary SMG epithelia to investigate the structural requirements of HS for FGF10-mediated epithelial morphogenesis. In BaF3/FGFR2b cells, heparin with at least 10 saccharides and 6-O-, 2-O-, and N-sulfates were required for maximal proliferation. During FGF10-mediated SMG epithelial morphogenesis, HS increased proliferation and end bud expansion. Defined heparin decasaccharide libraries showed that 2-O-sulfation with either an N- or 6-O-sulfate induced end bud expansion, whereas decasaccharides with 6-O-sulfation alone induced duct elongation. End bud expansion resulted from increased FGFR1b signaling, with increased FGFR1b, Fgf1, and Spry1 as well as increased Aqp5 expression, a marker of end bud differentiation. Duct elongation was associated with expression of Cp2L1, a marker of developing ducts. Collectively, these findings show that the size and sulfate patterns of HS modulate specific FGF10-mediated events, such as proliferation, duct elongation, end bud expansion, and differentiation, and provide mechanistic insight as to how the developmental localization of specific HS structures in tissues influences FGF10-mediated morphogenesis and differentiation. C1 [Patel, Vaishali N.; Likar, Karen M.; Cowherd, Samuel N.; Lassiter, Keyonica S.; Hoffman, Matthew P.] NIH, DHHS, NIDCR, LCDB,Matrix & Morphogenesis Unit, Bethesda, MD 20892 USA. [Likar, Karen M.] Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program, Bethesda, MD 20817 USA. [Zisman-Rozen, Simona; Sher, Ifat; Ron, Dina] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. [Yates, Edwin A.; Turnbull, Jeremy E.] Univ Liverpool, Sch Biol Sci, Liverpool L69 7ZB, Merseyside, England. RP Hoffman, MP (reprint author), NIH, DHHS, NIDCR, LCDB,Matrix & Morphogenesis Unit, Bldg 30-Rm 430,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM mhoffman@mail.nih.gov RI Yates, Edwin/I-4808-2013; OI Yates, Edwin/0000-0001-9365-5433 FU Intramural NIH HHS; Medical Research Council [G117/423] NR 46 TC 50 Z9 51 U1 0 U2 5 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 APR 4 PY 2008 VL 283 IS 14 BP 9308 EP 9317 DI 10.1074/jbc.M709995200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 280ZO UT WOS:000254465800061 PM 18230614 ER PT J AU Mahnke, Y Devevre, E Baurngaertner, P Matter, M Rufer, N Rorner, P Speiser, D AF Mahnke, Y. Devevre, E. Baurngaertner, P. Matter, M. Rufer, N. Rorner, P. Speiser, D. TI Tumour antigen specific CD8+T-cells from melanoma patients exert strong ex-vivo cytolytic activity SO SWISS MEDICAL WEEKLY LA English DT Meeting Abstract C1 [Mahnke, Y.] NIH, Bethesda, MD 20892 USA. [Devevre, E.; Baurngaertner, P.; Rorner, P.; Speiser, D.] Ludwig Inst Canc Res, Lausanne, Switzerland. [Rufer, N.] Multidisciplinary Oncol Ctr, Lausanne, Switzerland. [Matter, M.] CHUV, Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU E M H SWISS MEDICAL PUBLISHERS LTD PI MUTTENZ PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND SN 1424-7860 J9 SWISS MED WKLY JI Swiss Med. Wkly. PD APR 4 PY 2008 VL 138 SU 163 BP 17S EP 17S PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 288LK UT WOS:000254987700047 ER PT J AU Chanock, SJ Hunter, DJ AF Chanock, Stephen J. Hunter, David J. TI Genomics - When the smoke clears ... SO NATURE LA English DT Editorial Material C1 [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hunter, David J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov; dhunter@hsph.harvard.edu NR 6 TC 55 Z9 58 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 3 PY 2008 VL 452 IS 7187 BP 537 EP 538 DI 10.1038/452537a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 282KR UT WOS:000254567200024 PM 18385720 ER PT J AU Asangani, IA Rasheed, SAK Nikolova, DA Leupold, JH Colburn, NH Post, S Allgayer, H AF Asangani, I. A. Rasheed, S. A. K. Nikolova, D. A. Leupold, J. H. Colburn, N. H. Post, S. Allgayer, H. TI MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer SO ONCOGENE LA English DT Article DE pdcd4; miR-21; post-transcriptional regulation; invasion; CAM assay ID PROGRAMMED CELL-DEATH; GENE-EXPRESSION; MICRO-RNA; PROTEIN; TRANSFORMATION; GROWTH; TRANSLATION; TUMORIGENESIS; INITIATION; INHIBITION AB Tumor-suppressor Pdcd4 inhibits transformation and invasion and is downregulated in cancers. So far, it has not been studied as to whether miRNAs, suppressing target expression by binding to the 3'-UTR, regulate Pdcd4 or invasion. The present study was conducted to investigate the regulation of Pdcd4, and invasion/intravasation, by miRNAs. A bioinformatics search revealed a conserved target-site for miR-21 within the Pdcd4-3'UTR at 228-249 nt. In 10 colorectal cell lines, an inverse correlation of miR-21 and Pdcd4-protein was observed. Transfection of Colo206f-cells with miR-21 significantly suppressed a luciferase-reporter containing the Pdcd4-3'-UTR, whereas transfection of RKO with anti-miR-21 increased activity of this construct. This was abolished when a construct mutated at the miR-21/nt228-249 target site was used instead. Anti-miR-21-transfected RKO cells showed an increase of Pdcd4-protein and reduced invasion. Moreover, these cells showed reduced intra-vasation and lung metastasis in a chicken-embryo-metastasis assay. In contrast, overexpression of miR-21 in Colo206f significantly reduced Pdcd4-protein amounts and increased invasion, while Pdcd4-mRNA was unaltered. Resected normal/tumor tissues of 22 colorectal cancer patients demonstrated an inverse correlation between miR-21 and Pdcd4-protein. This is the first study to show that Pdcd4 is negatively regulated by miR-21. Furthermore, it is the first report to demonstrate that miR-21 induces invasion/intravasation/metastasis. C1 [Asangani, I. A.; Rasheed, S. A. K.; Nikolova, D. A.; Leupold, J. H.; Allgayer, H.] Univ Heidelberg, Med Fac Mannheim, Dept Expt Surg & Mol Oncol Solid Tumors, Collaborat Unit,German Canc Res Ctr, D-68167 Mannheim, Germany. [Asangani, I. A.; Rasheed, S. A. K.; Nikolova, D. A.; Leupold, J. H.; Allgayer, H.] DKFZ Heidelberg, Mannheim, Germany. [Colburn, N. H.] NCI, Basic Res Lab, Gene Regulat Sect, Frederick, MD 21701 USA. [Post, S.] Univ Heidelberg, Med Fac Mannheim, Dept Surg, D-6800 Mannheim, Germany. RP Allgayer, H (reprint author), Univ Heidelberg, Med Fac Mannheim, Dept Expt Surg & Mol Oncol Solid Tumors, Collaborat Unit,German Canc Res Ctr, D-68167 Mannheim, Germany. EM heike.allgayer@chir.ma.uni-heidelberg.de OI Rasheed, Suhail Ahmed Kabeer/0000-0002-7674-7560 NR 39 TC 984 Z9 1073 U1 31 U2 127 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 3 PY 2008 VL 27 IS 15 BP 2128 EP 2136 DI 10.1038/sj.onc.1210856 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 283FE UT WOS:000254621300003 PM 17968323 ER PT J AU Xu, Q Appella, DH AF Xu, Quin Appella, Daniel H. TI Aziridination of aliphatic alkenes catalyzed by N-heterocyclic carbene copper complexes SO ORGANIC LETTERS LA English DT Article ID OLEFIN AZIRIDINATION; EFFICIENT AZIRIDINATION; NITRENE TRANSFER; RHODIUM(II)-CATALYZED AZIRIDINATION; ENANTIOSELECTIVE AZIRIDINATION; ASYMMETRIC AZIRIDINATION; PORPHYRIN COMPLEX; CHIRAL AZIRIDINES; HIGHLY EFFICIENT; STABLE CARBENES AB A copper-catalyzed aziridination of aliphatic alkenes promoted by N-heterocyclic carbene ligands is described. The readily available catalyst IPrCu(DBM) can catalyze aziridination of a variety of aliphatic alkenes using alkenes as the limiting reagents. C1 [Xu, Quin; Appella, Daniel H.] NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Appella, DH (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, DHHS, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM appellad@niddk.nih.gov RI Xu, Qun /C-6996-2011 FU Intramural NIH HHS NR 91 TC 44 Z9 44 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 EI 1523-7052 J9 ORG LETT JI Org. Lett. PD APR 3 PY 2008 VL 10 IS 7 BP 1497 EP 1500 DI 10.1021/o1800288b PG 4 WC Chemistry, Organic SC Chemistry GA 281IK UT WOS:000254489900044 PM 18335951 ER PT J AU Gonzalez, FJ Shah, YA AF Gonzalez, Frank J. Shah, Yatrik A. TI PPAR alpha: Mechanism of species differences and hepatocarcinogenesis of peroxisome proliferators SO TOXICOLOGY LA English DT Article; Proceedings Paper CT Autumn Meeting of the British-Toxicology-Society CY SEP 10-11, 2007 CL Aberdeen, SCOTLAND SP British Toxicol Soc DE PPAR; peroxisome proliferators; humanized mice; nuclear receptors; microRNA; Wy-14,643; Fenofibrate; hepatocellular proliferation ID ACTIVATED-RECEPTOR-ALPHA; HEPATOCELLULAR PROLIFERATION; ACID WY-14,643; LIVER; MOUSE AB Peroxisome proliferator chemicals are classic non-genotoxic carcinogens. These agents cause liver cancers when chronically administered to rats and mice. Peroxisome proliferators include the widely prescribed lipid and cholesterol lowering fibrate drugs. In contrast to the results in rodents, there is no evidence that fibrates are associated with elevated risk of liver cancer or any other neoplasms in humans thus indicating a species difference in the hepatocarcinogenic response. The biological effects of peroxisome proliferators are mediated by the peroxisome proliferatoractivated receptor (PPAR)alpha. Ppar alpha-null mice are resistant to all of the pleiotropic effects of peroxisome proliferators, including cell proliferation and hepatocarcinogenesis. The mechanism of hepatocellular proliferation involves downregulation of the microRNA let-7c gene by PPAR(X. Let-7c controls levels of proliferative c-myc by destabilizing its mRNA. Thus, upon suppression of let-7c, c-myc mRNA and protein are elevated resulting in enhanced hepatocellular proliferation. In contrast, PPAR alpha-humanized mice, that respond to Wy-14,643 by lower serum triglycerides and induction of genes encoding fatty acid metabolizing enzymes, are resistant to peroxisome proliferator-induced cell proliferation and cancer. These mice do not exhibit downregulation of let-7c gene expression thus forming the basis for the resistance to hepatocellular carcinogenesis. Published by Elsevier Ireland Ltd. C1 [Gonzalez, Frank J.; Shah, Yatrik A.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS NR 18 TC 149 Z9 154 U1 0 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD APR 3 PY 2008 VL 246 IS 1 BP 2 EP 8 DI 10.1016/j.tox.2007.09.030 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 291AQ UT WOS:000255165100002 PM 18006136 ER PT J AU Hill, JW Hu, JJ Evans, MK AF Hill, Jeff W. Hu, Jennifer J. Evans, Michele K. TI OGG1 is degraded by calpain following oxidative stress and cisplatin exposure SO DNA REPAIR LA English DT Article DE OGG1; calpain; 8-oxoguanine; calcium; PEST ID ALZHEIMERS-DISEASE; INDUCED APOPTOSIS; CELL-DEATH; CANCER-PATIENTS; PEST SEQUENCES; LUNG-CANCER; DNA-DAMAGE; CROSS-TALK; T-CELLS; ACTIVATION AB Deficient repair activity for 8-hydroxy-2'-deoxyguanine (8-oxoguanine), a premutagenic oxidative DNA damage, has been observed in affected tissues in neurodegenerative diseases of aging, such as Alzheimer's disease, and in ischemia/reperfusion injury, type 2 diabetes mellitus, and cancer. These conditions have in common the accumulation of oxidative DNA damage, which is believed to play a role in disease progression, and loss of intracellular calcium regulation. These observations suggest that oxidative DNA damage repair capacity may be influenced by fluctuations in cellular calcium. We have identified human 8-oxoguanine-DNA glycosylase I (OGG1), the major 8-oxoguanine repair activity; as a specific target of the Ca2+-dependent protease Calpain I. Protein sequencing of a truncated partially calpain-digested OGG1 revealed that calpain recognizes OGGI for degradation at a putative PEST (proline, glutamic acid, serine, threonine) sequence in the C-terminus of the enzyme. Co-immunoprecipitation experiments showed that OGGI and Calpain I are associated in human cells. Exposure of HeLa cells to hydrogen peroxide or cisplatin resulted in the degradation of OGG1. Pretreatment of cells with the calpain inhibitor calpeptin resulted in inhibition of OGG1 proteolysis and suggests that OGG1 is a target for calpain-mediated degradation in vivo during oxidative stress- and cisplatin-induced apoptosis. Polymorphic OGG1 S326C was comparatively resistant to calpain digestion in vitro, yet was also degraded by a calpain-dependent pathway in vivo following DNA damaging agent exposure. The degradation of OGG1 by calpain may contribute to decreased 8-oxoguanine repair activity and elevated levels of 8-oxoguanine reported in tissues undergoing chronic oxidative stress, ischemia/reperfusion, and other cellular stressors known to produce perturbations of intracellular calcium homeostasis which activate calpain. (C) 2008 Elsevier B.V. All rights reserved. C1 [Evans, Michele K.] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. [Hill, Jeff W.; Hu, Jennifer J.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Div Canc Prevent & Control, Miami, FL 33136 USA. RP Evans, MK (reprint author), NIA, Cellular & Mol Biol Lab, NIH, 251 Bayview Blvd Suite 100, Baltimore, MD 21224 USA. EM evansmi@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000517-04]; NCI NIH HHS [CA73629, R29 CA073629, CA090898, R01 CA090898, R01 CA073629] NR 38 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD APR 2 PY 2008 VL 7 IS 4 BP 648 EP 654 DI 10.1016/j.dnarep.2008.01.003 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 293IA UT WOS:000255327800010 PM 18294929 ER PT J AU Shaw, P Kabani, NJ Lerch, JP Eckstrand, K Lenroot, R Gogtay, N Greenstein, D Clasen, L Evans, A Rapoport, JL Giedd, JN Wise, SP AF Shaw, Philip Kabani, Noor J. Lerch, Jason P. Eckstrand, Kristen Lenroot, Rhoshel Gogtay, Nitin Greenstein, Deanna Clasen, Liv Evans, Alan Rapoport, Judith L. Giedd, Jay N. Wise, Steve P. TI Neurodevelopmental trajectories of the human cerebral cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE brain development; cytoarchitecture; cognition; cerebral cortex; prefrontal cortex; primate ID CORTICAL THICKNESS; HUMAN BRAIN; CRITICAL PERIOD; EXECUTIVE FUNCTION; SENSITIVE PERIODS; LONGITUDINAL MRI; CHILDREN; ADOLESCENTS; CHILDHOOD; EVOLUTION AB Understanding the organization of the cerebral cortex remains a central focus of neuroscience. Cortical maps have relied almost exclusively on the examination of postmortem tissue to construct structural, architectonic maps. These maps have invariably distinguished between areas with fewer discernable layers, which have a less complex overall pattern of lamination and lack an internal granular layer, and those with more complex laminar architecture. The former includes several agranular limbic areas, and the latter includes the homotypical and granular areas of association and sensory cortex. Here, we relate these traditional maps to developmental data from noninvasive neuroimaging. Changes in cortical thickness were determined in vivo from 764 neuroanatomic magnetic resonance images acquired longitudinally from 375 typically developing children and young adults. We find differing levels of complexity of cortical growth across the cerebrum, which align closely with established architectonic maps. Cortical regions with simple laminar architecture, including most limbic areas, predominantly show simpler growth trajectories. These areas have clearly identified homologues in all mammalian brains and thus likely evolved in early mammals. In contrast, polysensory and high- order association areas of cortex, the most complex areas in terms of their laminar architecture, also have the most complex developmental trajectories. Some of these areas are unique to, or dramatically expanded in primates, lending an evolutionary significance to the findings. Furthermore, by mapping a key characteristic of these development trajectories ( the age of attaining peak cortical thickness) we document the dynamic, heterochronous maturation of the cerebral cortex through time lapse sequences ("movies"). C1 [Shaw, Philip; Eckstrand, Kristen; Lenroot, Rhoshel; Gogtay, Nitin; Greenstein, Deanna; Clasen, Liv; Rapoport, Judith L.; Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Wise, Steve P.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. [Kabani, Noor J.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3N1, Canada. [Lerch, Jason P.; Evans, Alan] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, 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 Gogtay, Nitin/A-3035-2008; 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 64 TC 663 Z9 668 U1 19 U2 112 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 APR 2 PY 2008 VL 28 IS 14 BP 3586 EP 3594 DI 10.1523/JNEUROSCI.5309-07.2008 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 283GA UT WOS:000254623500008 PM 18385317 ER PT J AU Amin, ND Zheng, YL Kesavapany, S Kanungo, J Guszczynski, T Sihag, RK Rudrabhatla, P Albers, W Grant, P Pant, HC AF Amin, Niranjana D. Zheng, Ya-Li Kesavapany, Sashi Kanungo, Jyotshnabala Guszczynski, Tad Sihag, Ram K. Rudrabhatla, Parvathi Albers, Wayne Grant, Philip Pant, Harish C. TI Cyclin-dependent kinase 5 phosphorylation of human septin SEPT5 (hCDCrel-1) modulates exocytosis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Cdk5; SEPT5; phosphorylation; syntaxin; secretion; hGH ID SYNAPTIC VESICLE ENDOCYTOSIS; DIRECTED PROTEIN-KINASE; NEURITE OUTGROWTH; CDK5; P35; SUBUNIT; ROLES; BRAIN; IDENTIFICATION; ACTIVATION AB Cyclin- dependent kinase 5 ( Cdk5) is predominantly expressed in the nervous system, where it is involved in neuronal migration, synaptic transmission, and survival. The role of Cdk5 in synaptic transmission is mediated by regulating the cellular functions of presynaptic proteins such as synapsin, Munc 18, and dynamin 1. Its multifunctional role at the synapse is complex and probably involves other novel substrates. To explore this possibility, we used a yeast two- hybrid screen of a human cDNA library with p35 as bait and isolated human septin 5 ( SEPT5), known also as hCDCrel- 1, as an interacting clone. Here we report that p35 associates with SEPT5 in GST ( glutathione S- transferase)- pull- down and coimmunoprecipitation assays. We confirmed that Cdk5/ p35 phosphorylates SEPT5 in vitro and in vivo and identified S327 of SEPT5 as a major phosphorylation site. A serine ( S)- to- alanine ( A) 327 mutant of SEPT5 bound syntaxin more efficiently than SEPT5 wild type. Additionally, coimmunoprecipitation from synaptic vesicle fractions and Cdk5 wild- type and knock- out lysates showed that phosphorylation of septin 5 by Cdk5/ p35 decreases its binding to syntaxin- 1. Moreover, mutant nonphosphorylated SEPT5 potentiated regulated exocytosis more than the wild type when each was expressed in PC12 cells. These data suggest that Cdk5 phosphorylation of human septin SEPT5 at S327 plays a role in modulating exocytotic secretion. C1 [Amin, Niranjana D.; Zheng, Ya-Li; Kanungo, Jyotshnabala; Sihag, Ram K.; Rudrabhatla, Parvathi; Albers, Wayne; Grant, Philip; Pant, Harish C.] Natl Inst Neurol Disorders & Stroke, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Kesavapany, Sashi] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117597, Singapore. [Guszczynski, Tad] NCI, Lab Cell & Dev Signalling, Frederick, MD 21702 USA. RP Pant, HC (reprint author), Natl Inst Neurol Disorders & Stroke, Neurochem Lab, NIH, Bldg 49,Room 2A28,49 Convent Dr, Bethesda, MD 20892 USA. EM panth@ninds.nih.gov NR 46 TC 34 Z9 37 U1 1 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 APR 2 PY 2008 VL 28 IS 14 BP 3631 EP 3643 DI 10.1523/JNEUROSCI.0453-08.2008 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 283GA UT WOS:000254623500013 PM 18385322 ER PT J AU Wang, J Seethala, RR Zhang, Q Gooding, W Van Waes, C Hasegawa, H Ferris, RL AF Wang, Jun Seethala, Raja R. Zhang, Qing Gooding, William Van Waes, Carter Hasegawa, Hitoshi Ferris, Robert L. TI Autocrine and paracrine chemokine receptor 7 activation in head and neck cancer: Implications for therapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; NF-KAPPA-B; LYMPHOID-ORGAN CHEMOKINE; MICE LACKING EXPRESSION; GROWTH-FACTOR RECEPTOR; NODE METASTASIS; CCR7; KINASE; RADIOTHERAPY; CHEMOTHERAPY AB Background The chemokine receptor 7 (CCR7) mediates survival and invasiveness of metastatic squamous cell carcinoma of the head and neck (SCCHN) to regional lymph nodes. Constitutive prosurvival signaling by the phosphoinositide-3 kinase/Akt pathway has been observed in SCCHN cells independent of epidermal growth factor receptor (EGFR) signaling. Methods Human SCCHN cell lines were treated with agents that block or activate CCR7-mediated signaling, and Akt activation, cell viability in the presence or absence of EGFR inhibition, and cisplatin-induced apoptosis (in the presence or absence of Akt inhibition) were assessed by immunoblotting, the MTT assay, and the detection of annexin V, respectively. Expression and secretion of chemokines by primary tumors, metastatic nodes, and benign nodes of patients with SCCHN were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The role of paracrine activation of CCR7 on tumor growth was analyzed by comparing the growth of orthotopic tumors derived from B7E3 murine oral carcinoma cells in wild-type BALB/c mice, in paucity of lymphoid T cell (plt, deficient in CCL19 and CCL21 expression) mice, and in plt mice in which the implanted B7E3 cells overexpressed CCR7 (n = 14 mice per group). Results In the absence of exogenous ligand treatment, blockade of CCR7 signaling reduced levels of phosphorylated (activated) Akt and decreased SCCHN cell viability by up to 59% (95% confidence interval [CI] = 58.2% to 59.8%), enhancing the effect of EGFR inhibition. CCR7 stimulation protected metastatic SCCHN cells from cisplatin-induced apoptosis in an Akt-dependent manner. Metastatic nodes expressed and secreted higher levels of CCL19 than benign nodes or primary tumors. CCR7-positive murine SCCHN tumors grew more slowly in plt mice than in control BALB/c mice (mean average tumor volume on day 20 = 12.2 and 26.5 mm(3), respectively; difference = 14.3 mm(3), 95% CI = 12.3 to 17.1 mm(3)). Conclusions Secretion of CCL19 and CCL21 by SCCHN cells and by paracrine sources combine to promote activation of CCR7 prosurvival signaling associated with tumor progression and disease relapse. CCR7 and its cognate chemokines may be useful biomarkers of SCCHN progression, and blockade of CCR7-mediated signaling may enhance the efficacy of platinum- and EGFR-based therapies. C1 [Wang, Jun; Zhang, Qing; Ferris, Robert L.] Univ Pittsburgh, Dept Otolaryngol, Inst Canc, Hillman Canc Ctr Res Wing, Pittsburgh, PA 15213 USA. [Gooding, William] Univ Pittsburgh, Sch Med, Dept Immunol, Biostat Facil, Pittsburgh, PA 15213 USA. [Seethala, Raja R.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. [Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. [Hasegawa, Hitoshi] Ehime Univ, Sch Med, Dept Internal Med, Shigenobu, Ehime 79102, Japan. RP Ferris, RL (reprint author), Univ Pittsburgh, Dept Otolaryngol, Inst Canc, Hillman Canc Ctr Res Wing, Rm 2-26b,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM ferrisrl@upmc.edu FU NCI NIH HHS [1R01 CA115902] NR 45 TC 44 Z9 48 U1 2 U2 6 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 APR 2 PY 2008 VL 100 IS 7 BP 502 EP 512 DI 10.1093/jnci/djn059 PG 11 WC Oncology SC Oncology GA 284NU UT WOS:000254713900012 PM 18364504 ER PT J AU Rodriguez, AC Schiffman, M Herrero, R Wacholder, S Hildesheim, A Castle, PE Solomon, D Burk, R AF Rodriguez, Ana Cecilia Schiffman, Mark Herrero, Rolando Wacholder, Sholom Hildesheim, Allan Castle, Philip E. Solomon, Diane Burk, Robert CA Proyecto Epidemiologico Guanacaste TI Rapid clearance of human papillomavirus and implications for clinical focus on persistent infections SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CERVICAL NEOPLASIA; COSTA-RICA; WOMEN; HPV; CANCER; RISK; GUANACASTE AB Health professionals and the public need to understand the natural history of human papillomavirus (HPV) infections of the cervix to best use the information provided by new molecular screening tests. We investigated outcomes of 800 carcinogenic HPV infections detected in 599 women at enrollment into a population-based cohort (Guanacaste, Costa Rica). For individual infections, we calculated cumulative proportions of three outcomes (viral clearance, persistence without cervical intraepithelial neoplasia grade 2 or worse [CIN2+], or persistence with new diagnosis of CIN2+) at successive 6-month time points for the first 30 months of follow-up. Cervical specimens were tested for carcinogenic HPV genotypes using an L1 degenerate-primer polymerase chain reaction method. Infections typically cleared rapidly, with 67% (95% confidence interval [CI] = 63% to 70%) clearing by 12 months. However, among infections that persisted at least 12 months, the risk of CIN2+ diagnosis by 30 months was 21% (95% CI = 15% to 28%). The risk of CIN2+ diagnosis was highest among women younger than 30 years with HPV-16 infections that persisted for at least 12 months (53%; 95% CI = 29% to 76%). These findings suggest that the medical community should emphasize persistence of cervical HPV infection, not single-time detection of HPV, in management strategies and health messages. C1 [Rodriguez, Ana Cecilia; Schiffman, Mark; Wacholder, Sholom; Hildesheim, Allan; Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Solomon, Diane] NCI, Div Canc Prevent, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Rodriguez, Ana Cecilia; Herrero, Rolando] INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Burk, Robert] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. RP Rodriguez, AC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS, Rm 5032, Rockville, MD 20852 USA. EM rodrigac@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU Intramural NIH HHS; NCI NIH HHS [CA78527, N01-CP21081, N01-CP33061, N01-CP40542, N01-CP50535, N01-CP81023, R01 CA078527, U01 CA078527] NR 25 TC 213 Z9 229 U1 1 U2 11 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 APR 2 PY 2008 VL 100 IS 7 BP 513 EP 517 DI 10.1093/jnci/djn044 PG 5 WC Oncology SC Oncology GA 284NU UT WOS:000254713900013 PM 18364507 ER PT J AU Taira, K Nakamura, S Nakano, K Maehara, D Okamoto, K Arimoto, S Loakes, D Worth, L Schaaper, RM Seio, K Sekine, M Negishi, K Negishi, T AF Taira, Kentaro Nakamura, Shintaro Nakano, Khota Maehara, Daisuke Okamoto, Keinosuke Arimoto, Sakae Loakes, David Worth, Leroy, Jr. Schaaper, Roel M. Seio, Kohji Sekine, Mitsuo Negishi, Kazuo Negishi, Tomoe TI Binding of MutS protein to oligonucleotides containing a methylated or an ethylated guanine residue, and correlation with mutation frequency SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE MutS; mismatch repair; O-6-methylguanine; O-6-ethylguanine; mutation ID DNA MISMATCH REPAIR; ESCHERICHIA-COLI; ALKYLATING-AGENTS; UV PHOTOPRODUCTS; MUTAGENESIS; BASE; MECHANISMS; RESPONSES; ADDUCTS; SYSTEM AB The MutS-based mismatch repair (MMR) system has been conserved from prokaryotes to humans, and plays important roles in maintaining the high fidelity of genomic DNA. MutS protein recognizes several different types of modified base pairs, including methylated guanine-containing base pairs. Here, we looked at the relationship between recognition and the effects of methylating versus ethylating agents on mutagenesis, using a MutS-deficient strain of E. coli. We find that while methylating agents induce mutations more effectively in a MutS-deficient strain than in wild-type, this genetic background does not affect mutagenicity by ethylating agents. Thus, the role of E. coli MMR with methylation-induced mutagenesis appears to be greater than ethylation-induced mutagenesis. To further understand this difference an early step of repair was examined with these alkylating agents. A comparison of binding affinities of MutS with O-6-alkylated guanine base paired with thymine, which could lead to transition mutations, versus cytosine which could not, was tested. Moreover, we compared binding of MutS to oligoduplexes containing different base pairs; namely, O-6-MeG:T, O-6-MeG:C, O-6-EtG:T, O-6-EtG:C, G:T and G:C. Dissociation constants (K-d), which reflect the strength of binding, followed the order G:T- > O-6-MeG:T- > O-6-EtG:T- = O-6-EtG:C- >= O-6-MeG:C- > G:C. These results suggest that a thymine base paired with O-6- methyl guanine is specifically recognized by MutS and therefore should be removed more efficiently than a thymine opposite O-6-ethylated guanine. Taken together, the data suggest that in E. coli, the MMR system plays a more significant role in repair of methylation-induced lesions than those caused by ethylation. (C) 2007 Elsevier B.V. All rights reserved. C1 [Worth, Leroy, Jr.; Schaaper, Roel M.] NIEHS, Res Triangle Pk, NC 27709 USA. [Loakes, David] MRC, Mol Biol Lab, Cambridge CB2 2QH, England. [Seio, Kohji; Sekine, Mitsuo] Tokyo Inst Technol, Fac Biosci & Biotechnol, Dept Life Sci, Yokohama, Kanagawa 2268501, Japan. [Negishi, Kazuo] Okayama Univ, Ctr Gene Res, Okayama 7008530, Japan. [Taira, Kentaro; Nakamura, Shintaro; Nakano, Khota; Maehara, Daisuke; Okamoto, Keinosuke; Arimoto, Sakae; Negishi, Tomoe] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan. RP Negishi, T (reprint author), Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan. EM isaka@pheasant.phann.okayama-u.ac.jp RI ARIMOTO, Sakae/B-1646-2011 FU Intramural NIH HHS [Z01 ES050170-08]; Medical Research Council [MC_U105178804] NR 28 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD APR 2 PY 2008 VL 640 IS 1-2 BP 107 EP 112 DI 10.1016/j.mrfmmm.2007.12.009 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 289UZ UT WOS:000255080700012 PM 18243250 ER PT J AU Wang, HR Liang, SY Burgdorf, J Wess, J Yeomans, J AF Wang, Haoran Liang, Shuyin Burgdorf, Jeffrey Wess, Jurgen Yeomans, John TI Ultrasonic Vocalizations Induced by Sex and Amphetamine in M2, M4, M5 Muscarinic and D2 Dopamine Receptor Knockout Mice SO PLOS ONE LA English DT Article AB Adult mice communicate by emitting ultrasonic vocalizations (USVs) during the appetitive phases of sexual behavior. However, little is known about the genes important in controlling call production. Here, we study the induction and regulation of USVs in muscarinic and dopaminergic receptor knockout (KO) mice as well as wild-type controls during sexual behavior. Female mouse urine, but not female rat or human urine, induced USVs in male mice, whereas male urine did not induce USVs in females. Direct contact of males with females is required for eliciting high level of USVs in males. USVs (25 to 120 kHz) were emitted only by males, suggesting positive state; however human-audible squeaks were produced only by females, implying negative state during male-female pairing. USVs were divided into flat and frequency-modulated calls. Male USVs often changed from continuous to broken frequency-modulated calls after initiation of mounting. In M2 KO mice, USVs were lost in about 70-80% of the mice, correlating with a loss of sexual interaction. In M5 KO mice, mean USVs were reduced by almost 80% even though sexual interaction was vigorous. In D2 KOs, the duration of USVs was extended by 20%. In M4 KOs, no significant differences were observed. Amphetamine dose-dependently induced USVs in wild-type males (most at 0.5 mg/kg i.p.), but did not elicit USVs in M5 KO or female mice. These studies suggest that M2 and M5 muscarinic receptors are needed for male USV production during male-female interactions, likely via their roles in dopamine activation. These findings are important for the understanding of the neural substrates for positive affect. C1 [Wang, Haoran; Liang, Shuyin; Yeomans, John] Univ Toronto, Dept Psychol, CTBC, Toronto, ON M5S 1A1, Canada. [Burgdorf, Jeffrey] Northwestern Univ, Falk Ctr Mol Therapeut, Evanston, IL USA. [Wess, Jurgen] NIH, NIDDK, Lab Bioorgan Chem, Bethesda, MD USA. RP Wang, HR (reprint author), Univ Toronto, Dept Psychol, CTBC, Toronto, ON M5S 1A1, Canada. EM haoranw@psych.toronto.edu; yeomans@psych.toronto.edu FU CIHR FX CIHR grants to JY NR 73 TC 41 Z9 42 U1 3 U2 11 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 APR 2 PY 2008 VL 3 IS 4 AR e1893 DI 10.1371/journal.pone.0001893 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 370XC UT WOS:000260795400025 PM 18382674 ER PT J AU Baker, E Dauter, Z Guss, M Einspahr, H AF Baker, Edward Dauter, Zbigniew Guss, Mitchell Einspahr, Howard TI Deposition of diffraction images to be discussed at the Open Meeting of the Commission on Biological Macromolecules of the IUCr in Osaka SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Editorial Material C1 [Baker, Edward] Univ Auckland, Sch Biol Sci, Auckland 1, New Zealand. [Dauter, Zbigniew] NCI, MCL, Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. [Guss, Mitchell] Univ Sydney, Sch Mol & Microbial Biosci, Sydney, NSW 2006, Australia. RP Baker, E (reprint author), Univ Auckland, Sch Biol Sci, Private Bag 92-019, Auckland 1, New Zealand. OI Guss, Mitchell/0000-0003-4259-6079 NR 0 TC 5 Z9 5 U1 0 U2 0 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 APR PY 2008 VL 64 BP 337 EP 338 DI 10.1107/S0907444908004915 PN 4 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 277XJ UT WOS:000254247700001 PM 18391400 ER PT J AU Agniswamy, J Joyce, MG Hammer, CH Sun, PD AF Agniswamy, Johnson Joyce, M. Gordon Hammer, Carl H. Sun, Peter D. TI Towards a rational approach for heavy-atom derivative screening in protein crystallography SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID X-RAY-DIFFRACTION; SITE-DIRECTED MUTAGENESIS; QUICK-SOAK METHOD; MASS-SPECTROMETRY; CRYSTAL; BINDING; RESOLUTION; TOOL; CRYSTALLIZATION; SYSTEM AB Heavy-atom derivatization is routinely used in protein structure determination and is thus of critical importance in structural biology. In order to replace the current trial-and-error heavy-atom derivative screening with a knowledge-based rational derivative-selection method, the reactivity of more than 40 heavy-atom compounds over a wide range of buffer and pH values was systematically examined using peptides which contained a single reactive amino-acid residue. Met-, Cys- and His-containing peptides were derivatized against Hg, Au and Pt compounds, while Tyr-, Glu-, Asp-, Asn-and Gln-containing peptides were assessed against Pb compounds. A total of 1668 reactive conditions were examined using mass spectrometry and were compiled into heavy-atom reactivity tables (http://sis.niaid.nih.gov/cgi-bin/heavyatom_reactivity.cgi). The results showed that heavy-atom derivatization reactions are highly linked to buffer and pH, with the most accommodating buffer being MES at pH 6. A group of 21 compounds were identified as most successful irrespective of ligand or buffer/pH conditions. To assess the applicability of the peptide heavy-atom reactivity to proteins, lysozyme crystals were derivatized with a list of peptide-reactive compounds that included both known and new compounds for lysozyme derivatization. The results showed highly consistent heavy-atom reactivities between the peptides and lysozyme. C1 [Agniswamy, Johnson; Joyce, M. Gordon; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Hammer, Carl H.] NIAID, Mass Spectrometry Lab, Res Technol Branch, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM psun@nih.gov FU Intramural NIH HHS NR 31 TC 5 Z9 5 U1 1 U2 2 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 APR PY 2008 VL 64 BP 354 EP 367 DI 10.1107/S0907444907068849 PN 4 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 277XJ UT WOS:000254247700003 PM 18391402 ER PT J AU Baker, E Dauter, Z Guss, M Einspahr, H AF Baker, Edward Dauter, Zbigniew Guss, Mitchell Einspahr, Howard TI Deposition of diffraction images to be discussed at the Open Meeting of the Commission on Biological Macromolecules of the IUCr in Osaka SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Editorial Material C1 [Baker, Edward] Univ Auckland, Sch Biol Sci, Auckland 1, New Zealand. [Dauter, Zbigniew] NCI, Argonne Natl Lab, MCL, Argonne, IL 60439 USA. [Guss, Mitchell] Univ Sydney, Sch Mol & Microbiol Sci, Sydney, NSW 2006, Australia. RP Baker, E (reprint author), Univ Auckland, Sch Biol Sci, Private Bag 92-019, Auckland 1, New Zealand. OI Guss, Mitchell/0000-0003-4259-6079 NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD APR PY 2008 VL 64 BP 231 EP 232 DI 10.1107/S1744309108007525 PN 4 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 281CE UT WOS:000254473200001 PM 18391414 ER PT J AU Moore, DF Goldin, E Gelderman, MP Robinson, C Baer, J Ries, M Elkahloun, A Brady, R Schiffmann, R AF Moore, David F. Goldin, Ehud Gelderman, Monique P. Robinson, Chevalia Baer, Jessica Ries, Markus Elkahloun, Abdel Brady, Roscoe Schiffmann, Raphael TI Apoptotic abnormalities in differential gene expression in peripheral blood mononuclear cells from children with Fabry disease SO ACTA PAEDIATRICA LA English DT Article; Proceedings Paper CT 7th International Symposium on Lysosomal Storage Diseases CY APR, 2007 CL Rome, ITALY DE apoptosis-inducing factor; enzyme replacement therapy; Fabry disease; neuronal apoptosis; inhibitory protein; peripheral blood mononuclear cells ID CEREBRAL HYPERPERFUSION; ENZYME REPLACEMENT; INHIBITORY PROTEIN; INFLAMMATION; REVERSAL; PATHWAY; PROFILE AB Aim: This study was designed to examine the effect of enzyme replacement therapy (ERT) on differential gene expression in peripheral blood mononuclear cells (PBMCs) of children with Fabry disease who had not previously been exposed to ERT. Methods: Thirteen children with Fabry disease (age range, 6.5-17.0 years) were studied as part of a 6-month, open-label study of ERT with agalsidase alfa. Paired blood samples were taken at the start of the study and after 6 months of ERT. Further blood samples were also taken from 16 age-matched control subjects. PBMCs were isolated and, following RNA extraction, differential gene expression analysis was performed using the Human Genome U 133 Plus 2.0 microarray. Results: Twenty-one genes were determined to be differentially expressed in PBMCs of ERT-naive children with Fabry disease compared with healthy controls; neuronal apoptosis inhibitory protein ranked as the most significantly differentially expressed gene. Comparison of gene expression in children with Fabry disease prior to and after ERT showed that two genes were significantly differentially expressed (p <= 0.05) following treatment; the expressed sequence tag (probe set ID, 243259-at) was downregulated, while expression of apoptosis-inducing factor was increased, possibly as an antioxidant counter-regulatory response. C1 [Goldin, Ehud; Robinson, Chevalia; Ries, Markus; Brady, Roscoe; Schiffmann, Raphael] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. [Moore, David F.] Univ Manitoba, Neurol Sect, Winnipeg, MB, Canada. [Gelderman, Monique P.] Fed Drug Adm, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Rockville, MD USA. [Baer, Jessica] NCI, Gene Express Lab, NIH, Frederick, MD 21701 USA. [Elkahloun, Abdel] Natl Inst Neurol Disorders & Stroke Microarray Co, Bethesda, MD USA. RP Schiffmann, R (reprint author), Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D03,900 Rockville Pike, Bethesda, MD 20892 USA. EM rs4e@nih.gov OI Ries, Markus/0000-0002-5054-5741 FU Intramural NIH HHS NR 23 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD APR PY 2008 VL 97 SU 457 BP 48 EP 52 DI 10.1111/j.1651-2227.2008.00654.x PG 5 WC Pediatrics SC Pediatrics GA 285BQ UT WOS:000254752700010 PM 18339188 ER PT J AU Kampmann, C Linhart, A Schiffmann, R Devereux, R AF Kampmann, C. Linhart, A. Schiffmann, R. Devereux, R. TI Agalsidase alfa reduces cardiac mass in patients with Fabry disease with left ventricular hypertrophy: results of a centralized, blinded echocardiographic assessment SO ACTA PAEDIATRICA LA English DT Meeting Abstract C1 [Kampmann, C.] Johannes Gutenberg Univ Mainz, Mainz, Germany. [Linhart, A.] Charles Univ Prague, Prague, Czech Republic. [Schiffmann, R.] NIH, Bethesda, MD 20892 USA. [Devereux, R.] Cornell Univ, Weill Med Coll, New York, NY 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 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD APR PY 2008 VL 97 SU 457 BP 108 EP 108 PG 1 WC Pediatrics SC Pediatrics GA 285BQ UT WOS:000254752700044 ER PT J AU Dixit, R Sharma, A Patole, MS Shouche, YS AF Dixit, Rajnikant Sharma, Arun Patole, Millind S. Shouche, Yogesh S. TI Molecular and phylogenetic analysis of a novel salivary defensin cDNA from malaria vector Anopheles stephensi SO ACTA TROPICA LA English DT Article DE mosquito; salivary gland; malaria vector; defensin; immunity ID INDUCIBLE ANTIBACTERIAL PEPTIDE; INSECT DEFENSIN; MOSQUITO; PARASITE; GAMBIAE; GLAND; GENE; INVASION; IMMUNITY AB Manipulating the endogenous immune responses of the mosquito such as temporal and spatial expression of antimicrobial peptides may help in the development of a refractory mosquito, unable to transmit malaria. In mosquito several small antimicrobial peptides are activated locally in the midgut and salivary glands upon Plasmodium infection. Anopheles stephensi, the major urban malaria vector in India, has been considered as an important insect model to study vector-parasite interactions; however, so far no reports are available on the antimicrobial peptides from this mosquito species. In the present study, we report identification and molecular characterization of a novel cDNA encoding defensin like peptide, isolated from the salivary gland subtractive hybridization cDNA library of mosquito A. stephensi. Defensin cDNA is 396 base pair long, bearing an open reading frame of 96 amino acids. Deduced amino acid sequence of A. stephensi defensin (Astp_def) contains a signal peptide sequence of 24 amino acids followed by 32-amino acids long putative propeptide domain and a 40-amino acid mature peptide domain carrying 23-amino acid long consensuses sequence signature of insect defensin. Mature peptide of Astp_def carries six conserved cysteine residues, with a predicted molecular weight of 4.20 kDa, and isoelectric point of 8.30, characteristic features of cationic defensins. Amino acid sequence similarity and phylogenetic analysis indicated a higher variation in the pre-propeptide region, as compared to the mature defensin peptide, assuring the presence of finely tuned immune responses to counter pathogens. (C) 2008 Elsevier B.V. All rights reserved. C1 [Dixit, Rajnikant; Patole, Millind S.; Shouche, Yogesh S.] Natl Ctr Cell Sci, Mol Biol Unit, Pune 411007, Maharashtra, India. [Sharma, Arun] Natl Inst Malaria Res, Delhi 110054, India. RP Dixit, R (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM dixit2k@yahoo.com RI DIXIT, RAJNIKANT/D-2566-2009; SHOUCHE, YOGESH/C-1231-2009 OI DIXIT, RAJNIKANT/0000-0002-3536-8329; NR 20 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0001-706X J9 ACTA TROP JI Acta Trop. PD APR PY 2008 VL 106 IS 1 BP 75 EP 79 DI 10.1016/j.actatropica.2008.01.001 PG 5 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA 295PT UT WOS:000255487100012 PM 18275930 ER PT J AU Ghitza, UE Epstein, DH Preston, KL AF Ghitza, Udi E. Epstein, David H. Preston, Kenzie L. TI Contingency management reduces injection-related HIV risk behaviors in heroin and cocaine using outpatients SO ADDICTIVE BEHAVIORS LA English DT Article DE contingency management; substance abuse treatment; HIV; opiate; cocaine; methadone maintenance ID SUBSTANCE USE DISORDERS; DRUG-USERS; METHADONE-MAINTENANCE; ABSTINENCE REINFORCEMENT; RANDOMIZED-TRIAL; METAANALYSIS; RELIABILITY; DEPENDENCE; INCENTIVES; REDUCTION AB Intravenous drug use is a major vector of HIV transmission. We assessed whether contingency management (CM), in which participants cam reinforcers for drug abstinence, reduces HIV risk behaviors in methadone-maintained opiate- and cocaine-using outpatients. Participants (n = 116) were randomly assigned to prize-based CM or to receipt of prize draws noncontingently on a schedule yoked to the CM group. Both groups received methadone and individual counseling throughout treatment. The HIV-Risk Taking Behaviour Scale was administered in written questionnaire form at 2-week intervals (HRBS; [Darke, S., Hall, W, Heather, N., Ward, J., & Wodak, A. (1991). The reliability and validity of a scale to measure HIV risk-taking behaviour among intravenous drug users. AIDS, 5, 181-185]). A mediation analysis was conducted to determine whether abstinence from opiates and cocaine mediated the effect of CM on HRBS scores. Changes in HRBS scores over time differed significantly by treatment (F(9,334)=2.4,p<0.05), with HRBS scores decreasing over time in the CM group to a greater extent than in the noncontingent control group. Participants in the CM group had significantly lower rates of simultaneous cocaine/opiate-positive urine specimens than those in the noncontingent control group during CM treatment (F(1,1 1 1)=6.8, p=0.01). The relationship between treatment condition and HRBS scores was mediated by abstinence. CM targeted toward cocaine and heroin use produces significant reductions in injection-related drug-taking behaviors associated with heightened risk for getting or transmitting HIV. Published by Elsevier Ltd. C1 [Ghitza, Udi E.; Epstein, David H.; Preston, Kenzie L.] NIDA, NIH, Clin Pharmacol & Therapeut Branch, Treatment Sect,IRP, Baltimore, MD 21224 USA. RP Ghitza, UE (reprint author), NIDA, NIH, Clin Pharmacol & Therapeut Branch, Treatment Sect,IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ghitzau@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS [Z01 DA000175-13, Z99 DA999999] NR 39 TC 12 Z9 12 U1 2 U2 2 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 APR PY 2008 VL 33 IS 4 BP 593 EP 604 DI 10.1016/j.addbeh.2007.11.009 PG 12 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 266EA UT WOS:000253413300008 PM 18068905 ER PT J AU Narva, AS AF Narva, Andrew S. TI Reducing the burden of chronic kidney disease among American Indians SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE chronic kidney disease; American Indians; diabetes; chronic care model; Indian Health Service ID STAGE RENAL-DISEASE AB American Indians (AIs) and Alaska Natives (ANs) have experienced a dramatic rise in type 2 diabetes and associated complications, including chronic kidney disease (CKD) over the past half century. At the end of 2005, the national prevalence of end-stage renal disease (ESRD) in AIs/ANs was 2.5 times greater than that for white Americans, with rates significantly higher among communities of the southwest United States. Evidence of CKD among AIs/ANs with diabetes includes abnormal protein excretion in 30% and estimated glomerular filtration rate (eGFR) < 60 mL/min/m(2) in 17%. In order to address the growing burden of CKD, the Indian Health Service established the Kidney Disease Program to improve the screening of and the management of diabetics with CKD. Routine reporting of eGFR, yearly monitoring of protein excretion, utilization of renin-angiotensin system (RAS) antagonists, and aggressive control of blood pressure were implemented in association with enhanced patient and provider education. By 2006, 82% of hypertensive diabetics were receiving a RAS antagonist. Implementation of these efforts has been associated with a 31% decrease in ESRD incidence among AIs/ANs with diabetes. This program of improvements in CKD care implemented by a federal agency serving a high-risk population with limited resources may be a useful model for others. (c) 2008 by the National Kidney Foundation, Inc. C1 NIDDK, Natl Kidney Dis Educ Program, DKUH, NIH, Bethesda, MD 20892 USA. RP Narva, AS (reprint author), NIDDK, Natl Kidney Dis Educ Program, DKUH, NIH, 2 Democracy Plaza,Room 645,6707 Democracy Blvd,MS, Bethesda, MD 20892 USA. EM narvaa@nidatk.nih.gov NR 14 TC 16 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD APR PY 2008 VL 15 IS 2 BP 168 EP 173 DI 10.1053/j.ackd.2008.01.011 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 280HO UT WOS:000254416800012 PM 18334242 ER PT J AU Lauretani, F Semba, RD Bandinelli, S Ray, AL Ruggiero, C Cherubini, A Guralnik, JM Ferrucci, L AF Lauretani, Fulvio Semba, Richard D. Bandinelli, Stefania Ray, Amanda L. Ruggiero, Carmelinda Cherubini, Antonio Guralnik, Jack M. Ferrucci, Luigi TI Low plasma selenium concentrations and mortality among older community-dwelling adults: the InCHIANTI Study SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID SERUM SELENIUM; HEART-DISEASE; CANCER; PEOPLE; RISK; ANTIOXIDANTS; WOMEN; MEN AB Aims: We examined the relationship between plasma selenium levels at enrollment and all-cause mortality over a 6-year period among participants in the InCHIANTI study. Methods: 1042 men and women >= 65 years from the InCHIANTI study, a population-based study of older adults living in the Chianti region of Tuscany, a population-based cohort in Tuscany, Italy. Plasma selenium was measured at enrollment (1998-2000), and vital status was ascertained until May 2006. Results: During follow-up, 237 participants (22.7%) died. At enrollment, mean (SD) plasma selenium concentrations among participants who survived or died were 0.96 (0.14) and 0.87 (0.18) mu mol/L (p<0.0001), respectively. The proportion of participants who died, from lowest to highest quartile of selenium, was 41.3, 27.0, 18.1 and 13.5% (p<0.0001 by Mantel-Haenszel chi-square). After adjusting for age, sex, education, and chronic diseases, adults in the lowest quartile of plasma selenium at enrollment had higher mortality compared with those in the highest quartile (Hazard Ratio (HR) 1.60, 95% Confidence Interval (CI) 1.04-2.47, p=0.034). Conclusion: Low plasma selenium may be an independent predictor of mortality among older adults living in the community. C1 [Lauretani, Fulvio; Ruggiero, Carmelinda; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Gerontol Res Ctr, NIH,Clin Res Branch, Baltimore, MD 21224 USA. [Lauretani, Fulvio] Tuscany Reg Agcy, Florence, Italy. [Semba, Richard D.; Ray, Amanda L.] Johns Hopkins Sch Med, Baltimore, MD USA. [Bandinelli, Stefania] Azienda Sanitaria Firenze, Florence, Italy. [Ruggiero, Carmelinda; Cherubini, Antonio] Univ Perugia, Sch Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Gerontol Res Ctr, NIH,Clin Res Branch, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM FerrucciLu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Cherubini, Antonio/0000-0003-0261-9897 FU Intramural NIH HHS [Z01 AG000015-49, Z99 AG999999]; NIA NIH HHS [R01 AG 027012, N01 AG 50002, N01 AG 821336, N01 AG 916413, R01 AG027012] NR 29 TC 14 Z9 14 U1 1 U2 2 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD APR PY 2008 VL 20 IS 2 BP 153 EP 158 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 302HJ UT WOS:000255959100009 PM 18431083 ER PT J AU Morrow, M Valentin, A Little, R Yarchoan, R Pavlakis, GN AF Morrow, Matthew Valentin, Antonio Little, Richard Yarchoan, Robert Pavlakis, George N. TI A splenic marginal zone-like peripheral blood CD27(+) B220(-)B cell population is preferentially depleted in HIV type 1-infected individuals SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HYPER-IGM SYNDROME; MEMORY B-CELLS; PNEUMOCOCCAL POLYSACCHARIDE VACCINE; ACTIVE ANTIRETROVIRAL THERAPY; CD40 LIGAND DYSREGULATION; INFECTED INDIVIDUALS; LYMPHOCYTE DYSFUNCTIONS; SEROPOSITIVE PATIENTS; T-CELLS AB Peripheral blood CD27(+) B cells are reduced in HIV-1- infected individuals. In healthy individuals, the human peripheral blood CD27(+) B cell pool consists of two subsets defined by the expression, or lack thereof, of the CD45 isoform B220. We investigated the presence of circulating B220(+) and B220(+) memory B cells in HIV+ individuals and found that the reduction in CD27(+) memory B cells occurs primarily among CD27(+) B220(+) B cells. Studies conducted using healthy controls indicate that CD27(+) B220(+) B cells have a splenic marginal zone like the immunophenotype IgM(hi)IgD(lo)CD21(+) CD23(-), express TLR9, and proliferate and secrete IgG and IgM in response to B cell-specific ODN. CD27(+) B220(+) B cells have the immunophenotype IgM(lo)IgD(hi)CD21(+) CD23(+), express activation- induced cytidine deaminase, and proliferate in response to SAC but do not secrete immunoglobulin. The AICD expression, along with CD86 expression, by CD27(+) B220(+) suggests these cells are of germinal center origin. The preferential depletion of CD27(+) B220(+) B cells mirrors alterations in spleen morphology and resident B cell populations due to HIV infection reported by other investigators and may play an important role in the defective B cell immunity against T-independent pathogens such as pneumococcus observed in HIV-1- infected individuals. C1 [Morrow, Matthew; Valentin, Antonio; Pavlakis, George N.] NCI, Ctr Canc Res, Vaccine Branch, Human Retrovirus Sect, Frederick, MD 21702 USA. [Little, Richard; Yarchoan, Robert] NCI, Ctr Canc Res, HIV & AIDS Maligancy Branch, Bethesda, MD 20895 USA. RP Pavlakis, GN (reprint author), NCI, Ctr Canc Res, Vaccine Branch, Human Retrovirus Sect, Bldg 535,Room 210, Frederick, MD 21702 USA. EM pavlakis@ncifcrf.gov FU Intramural NIH HHS [Z01 BC010750-02] NR 51 TC 16 Z9 16 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 APR PY 2008 VL 24 IS 4 BP 621 EP 633 DI 10.1089/aid.2007.0186 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 294GV UT WOS:000255394900012 PM 18426338 ER PT J AU Signore, C Ueland, PM Troendle, J Mills, JL AF Signore, Caroline Ueland, Per Magne Troendle, James Mills, James L. TI Choline concentrations in human maternal and cord blood and intelligence at 5 y of age SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID PLASMA HOMOCYSTEINE; BRAIN-DEVELOPMENT; DIETARY CHOLINE; SPATIAL MEMORY; SUPPLEMENTATION; AVAILABILITY; ALTERS; RATS; NEUROTRANSMISSION; STIMULATION AB Background: Animal studies indicate that maternal prenatal choline supplementation leads to permanent enhancement of attention and spatial memory abilities in offspring, whereas dietary choline restriction during pregnancy impairs cognitive function in offspring. The association between gestational choline concentrations and neurodevelopmental outcome in humans has not been studied. Objective: Our objective was to assess the relation between maternal and cord blood choline concentrations and child intelligence quotient (IQ) scores at 5 y of age. Design: With data and samples from a prospective study (n = 404 maternal-child pairs), serum concentrations of free and total choline were measured in maternal serum at 4 gestational age intervals (16-18 wk, 24-26 wk, 30-32 wk, and 36-38 wk) and in cord blood. Child IQ at 5 y of age was assessed with the Wechsler Preschool and Primary Scale of Intelligence-Revised. Multiple regression techniques were used to estimate the relation between choline concentrations and Full Scale IQ, Verbal and Performance IQ, and subscales that assess spatial relation and memory ability while adjusting for other factors that affect IQ. Results: There was no effect at gestational ages 16-18 wk, 24-26 wk, 30-32 wk, and 36-38 wk or in cord blood of serum concentrations of free or total choline on Full Scale child IQ or on selected scales related to visuospatial processing and memory. Conclusion: Gestational and newborn choline concentrations in the physiologic range showed no correlation with childhood intelligence. C1 [Mills, James L.] NICHD, DESPR, NIH, DHHS, Bethesda, MD 20892 USA. [Signore, Caroline; Mills, James L.] NICHD, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Troendle, James] NICHD, Biometry & Math Stat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Ueland, Per Magne] Univ Bergen, Inst Med, Pharmacol Sect, Bergen, Norway. [Ueland, Per Magne] Haukeland Hosp, N-5021 Bergen, Norway. RP Mills, JL (reprint author), NICHD, DESPR, NIH, DHHS, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. EM millsj@mail.nih.gov RI Ueland, Per/C-7340-2013 FU Intramural NIH HHS [Z01 HD008802-01] NR 38 TC 29 Z9 30 U1 1 U2 6 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 APR PY 2008 VL 87 IS 4 BP 896 EP 902 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 288UT UT WOS:000255012000015 PM 18400712 ER PT J AU Hjuler, T Poulsen, G Wohlfahrt, J Kaltoft, M Biggar, RJ Melbye, M AF Hjuler, Thomas Poulsen, Gry Wohlfahrt, Jan Kaltoft, Margit Biggar, Robert J. Melbye, Mads TI Genetic susceptibility to severe infection in families with invasive pneumococcal disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; genetic predisposition to disease; pneumococcal infections; population ID MANNOSE-BINDING LECTIN; STREPTOCOCCUS-PNEUMONIAE; PREMATURE DEATH; ADULT ADOPTEES; MENINGOCOCCAL DISEASE; YOUNG-CHILDREN; RISK; CARRIAGE; GENOTYPE; POLYMORPHISMS AB Severe infections may be influenced by genetic constitution. The authors examined familial aggregation of invasive infections, using invasive pneumococcal disease (IPD) as the index condition to ascertain families at risk. From Danish national registers, they identified relatives of persons with IPD from 1977 through 2005. Risks of IPD, bacterial meningitis, septicemia, and any invasive infection were analyzed for relatives of IPD cases in a prospective cohort study (23 million person-years). In total, 43,134 persons were found to have an IPD case in the family. The authors observed an increased risk of invasive infections in relatives of IPD cases most likely sharing the same household (parents, offspring, siblings, half-siblings), but only regarding those events within 1 year of the index IPD diagnosis (rate ratio = 7.4, 95% confidence interval: 2.4, 23.0). After 1 year, there were no increased risks of severe infections, including IPD, in close relatives. For other relatives, no increased risks of severe infections were observed at any time. No aggregation of invasive infections in IPD relatives was found, other than for close events among relatives who most likely shared the same household. Thus, at the population level, genetic constitution appears of little importance in the development of IPD and other severe infections. C1 [Hjuler, Thomas; Poulsen, Gry; Wohlfahrt, Jan; Biggar, Robert J.; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen S, Denmark. [Kaltoft, Margit] Statens Serum Inst, Dept Bacteriol Mycol & Parasitol, DK-2300 Copenhagen, Denmark. [Biggar, Robert J.] NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RP Hjuler, T (reprint author), Statens Serum Inst, Dept Epidemiol, Artillerivej 5, DK-2300 Copenhagen S, Denmark. EM tta@ssi.dk NR 34 TC 10 Z9 11 U1 0 U2 0 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 APR 1 PY 2008 VL 167 IS 7 BP 814 EP 819 DI 10.1093/aje/kwm376 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 281AW UT WOS:000254469500008 PM 18227098 ER PT J AU Matthews, CE Chen, KY Freedson, PS Buchowski, MS Beech, BM Pate, RR Troiano, RP AF Matthews, Charles E. Chen, Kong Y. Freedson, Patty S. Buchowski, Maciej S. Beech, Bettina M. Pate, Russell R. Troiano, Richard P. TI Amount of time spent in sedentary behaviors in the united states, 2003-2004 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE energy metabolism; monitoring; ambulatory; motor activity; obesity; population surveillance ID OF-SPORTS-MEDICINE; AMERICAN-HEART-ASSOCIATION; PHYSICAL-ACTIVITY; PUBLIC-HEALTH; PLASMA-GLUCOSE; ADULTS; ACCELEROMETER; OBESITY; RISK; RECOMMENDATION AB Sedentary behaviors are linked to adverse health outcomes, but the total amount of time spent in these behaviors in the United States has not been objectively quantified. The authors evaluated participants from the 2003-2004 National Health and Nutrition Examination Survey aged >= 6 years who wore an activity monitor for up to 7 days. Among 6,329 participants with at least one 10-hour day of monitor wear, the average monitor-wearing time was 13.9 hours/day (standard deviation, 1.9). Overall, participants spent 54.9% of their monitored time, or 7.7 hours/day, in sedentary behaviors. The most sedentary groups in the United States were older adolescents and adults aged >= 60 years, and they spent about 60% of their waking time in sedentary pursuits. Females were more sedentary than males before age 30 years, but this pattern was reversed after age 60 years. Mexican-American adults were significantly less sedentary than other US adults, and White and Black females were similarly sedentary after age 12 years. These data provide the first objective measure of the amount of time spent in sedentary behavior in the US population and indicate that Americans spend the majority of their time in behaviors that expend very little energy. C1 [Matthews, Charles E.; Beech, Bettina M.] Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Dept Med,Sch Med, Nashville, TN 37232 USA. [Chen, Kong Y.] NIDDK, Div Intramural Res, Bethesda, MD USA. [Freedson, Patty S.] Univ Massachusetts, Dept Kinesiol, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. [Buchowski, Maciej S.] Vanderbilt Univ, Dept Med, Sch Med, Div Gastroenterol Hepatol & Nutr, Nashville, TN 37232 USA. [Pate, Russell R.] Univ S Carolina, Dept Exercise Sci, Norman J Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Troiano, Richard P.] NCI, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. RP Matthews, CE (reprint author), Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Dept Med,Sch Med, 2525 W End Ave,Suite 600, Nashville, TN 37232 USA. EM charles.matthews@vanderbilt.edu RI Buchowski, Maciej/A-2683-2008; matthews, Charles/E-8073-2015; OI Buchowski, Maciej/0000-0002-0566-1743; matthews, Charles/0000-0001-8037-3103; Troiano, Richard/0000-0002-6807-989X; Chen, Kong/0000-0002-0306-1904 FU NIDDK NIH HHS [R01 DK069465, R01 DK069465-04] NR 36 TC 821 Z9 829 U1 29 U2 127 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 APR 1 PY 2008 VL 167 IS 7 BP 875 EP 881 DI 10.1093/aje/kwm390 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 281AW UT WOS:000254469500015 PM 18303006 ER PT J AU Hawk, ET Viner, JL AF Hawk, Ernest T. Viner, Jaye L. TI Statins in esophageal cancer cell lines: Promising lead? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID COA REDUCTASE INHIBITOR; BARRETTS-ESOPHAGUS; COLORECTAL-CANCER; INCREASES PROLIFERATION; COLON CARCINOGENESIS; MOLECULAR-BIOLOGY; ICR MICE; RISK; ADENOCARCINOMA; MUTATIONS AB Barrett's-associated esophageal adenocarcinoma (BEAC) is an important health concern in many western populations owing to its increasing incidence and the paucity of effective treatments. Statins have recently been suggested to induce anticancer effects against a variety of cancers in several, but not all, in vitro, in vivo, and epidemiologic studies. In the accompanying article by Ogunwobi and Beales, three statins were shown to inhibit proliferation and stimulate apoptosis in two EAC cell lines. These effects were achieved by reducing Ras, extracellular signal-regulated kinase (ERK), and protein kinase B (Akt)-related cellular signaling. Although these results are promising, they are clearly preliminary, and much additional work is needed to confirm or refute the potential anticancer effects of statins in human BEAC. In addition, the work of Ogunwobi and Beales highlights the importance of developing better, more predictive in vitro and in vivo models of BEAC, and of taking promising, low-risk agents, such as statins, into early-phase therapeutic and preventive clinical trials involving cancer patients and patients with Barrett's metaplasia/dysplasia, respectively. C1 [Hawk, Ernest T.; Viner, Jaye L.] NCI, Off Ctr Training & Resources, Bethesda, MD USA. RP Hawk, ET (reprint author), NCI, 6116 Execut Blvd,Suite 700, Bethesda, MD 20892 USA. NR 42 TC 5 Z9 5 U1 0 U2 0 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 APR PY 2008 VL 103 IS 4 BP 838 EP 841 DI 10.1111/j.1572-0241.2007.01768.x PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 283VS UT WOS:000254665200005 PM 18371147 ER PT J AU Dotson, VM Resnick, SM Zonderman, AB AF Dotson, Vonetta M. Resnick, Susan M. Zonderman, Alan B. TI Differential association of concurrent, baseline, and average depressive symptoms with cognitive decline in older adults SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE aging; subclinical depression; cognition ID DWELLING ELDERLY PERSONS; ALZHEIMERS-DISEASE; TEMPORAL RELATION; AGE; POPULATION; RISK; DEMENTIA; HISTORY; SAMPLE; BRAIN AB Objectives: The impact of depressive symptoms on cognitive decline in older adults remains unclear due to inconsistent findings in the literature. It is also unclear whether effects of depressive symptoms on cognitive decline vary with age. This study investigated the effect of concurrent, baseline, and average depressive symptoms on cognitive functioning and decline, and examined the interactive effect of age and depressive symptoms on cognition. Design: Prospective observational design with examination of cognitive performance and depressive symptoms at 1- to 2-year intervals for up to 26 years. Setting: Baltimore Longitudinal Study of Aging, National Institute on Aging. Participants: One thousand five hundred eighty-six dementia-free adults 50 years of age and older. Measurements: Scores over time on the Center for Epidemiologic Studies Depression Scale and measures of learning and memory, attention and executive functions, verbal and language abilities, visuospatial functioning, and general cognitive status. Results: Increased depressive symptoms were associated with poor cognitive functioning and cognitive decline in multiple domains. Concurrent, baseline, and average depressive symptoms had differential associations with cognition. Average depressive symptoms, a measure of chronic symptoms, seemed to show the most widespread effects on cognitive abilities. Effects of depressive symptoms on some frontal functions were greater with advancing age. Conclusion: Depressive symptoms are associated with poor cognitive functioning and cognitive decline, particularly with advancing age. The widespread impact of average depressive symptoms on cognition suggests that clinicians should consider the chronicity of depressive symptoms when evaluating cognitive functioning in older adults. C1 [Dotson, Vonetta M.; Resnick, Susan M.; Zonderman, Alan B.] NIA, Lab Personal & Cognit, NIH, Ctr Biomed Res,IRP, Baltimore, MD 21224 USA. RP Dotson, VM (reprint author), NIA, Lab Personal & Cognit, NIH, Ctr Biomed Res,IRP, 251 Bayview Blvd,Suite 100,Room 04B316, Baltimore, MD 21224 USA. EM dotsonv@mail.nih.gov RI Dotson, Vonetta/K-6090-2015; OI Dotson, Vonetta/0000-0002-3043-3320; Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS [Z01 AG000185-19, Z01 AG000185-18] NR 47 TC 75 Z9 77 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD APR PY 2008 VL 16 IS 4 BP 318 EP 330 DI 10.1097/JGP.0b013e3181662a9c PG 13 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 282OM UT WOS:000254577100009 PM 18378557 ER PT J AU Lasky-Su, J Lyon, HN Emilsson, V Heid, IM Molony, C Raby, BA Lazarus, R Klanderman, B Soto-Quiros, ME Avila, L Silverman, EK Thorleifsson, G Thorsteinsdottir, U Kronenberg, F Vollmert, C Illig, T Fox, CS Levy, D Laird, N Ding, X McQueen, MB Butler, J Ardlie, K Papoutsakis, C Dedoussis, G O'Donnell, CJ Wichmann, HE Celedon, JC Schadt, E Hirschhorn, J Weiss, ST Stefansson, K Lange, C AF Lasky-Su, Jessica Lyon, Helen N. Emilsson, Valur Heid, Iris M. Molony, Cliona Raby, Benjamin A. Lazarus, Ross Klanderman, Barbara Soto-Quiros, Manuel E. Avila, Lydiana Silverman, Edwin K. Thorleifsson, Gudmar Thorsteinsdottir, Unnur Kronenberg, Florian Vollmert, Caren Illig, Thomas Fox, Caroline S. Levy, Daniel Laird, Nan Ding, Xiao McQueen, Matt B. Butler, Johannah Ardlie, Kristin Papoutsakis, Constantina Dedoussis, George O'Donnell, Christopher J. Wichmann, H. -Erich Celedon, Juan C. Schadt, Eric Hirschhorn, Joel Weiss, Scott T. Stefansson, Kari Lange, Christoph TI On the replication of genetic associations: Timing can be everything! SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BODY-MASS INDEX; RECEPTOR LEPR POLYMORPHISMS; CHILDHOOD OBESITY; CHILDREN; LINKAGE; VARIANT; DESIGN; ASTHMA; SPECTROMETRY; POPULATION AB The failure of researchers to replicate genetic-association findings is most commonly attributed to insufficient statistical power, population stratification, or various forms of between-study heterogeneity or environmental influences.' Here, we illustrate another potential cause for nonreplications that has so far not received much attention in the literature. We illustrate that the strength of a genetic effect can vary by age, causing "age-varying associations." If not taken into account during the design and the analysis of a study, age-varying genetic associations can cause nonreplication. By using the 100K SNP scan of the Framingham Heart Study, we identified an age-varying association between a SNP in ROBO1 and obesity and hypothesized an age-gene interaction. This finding was followed up in eight independent samples comprising 13,584 individuals. The association was replicated in five of the eight studies, showing an age-dependent relationship (one-sided combined p = 3.92 x 10(-9), combined p value from pediatric cohorts = 2.21 X 10(-8), combined p value from adult cohorts = 0.00422). Furthermore, this study illustrates that it is difficult for cross-sectional study designs to detect age-varying associations. If the specifics of age- or time-varying genetic effects are not considered in the selection of both the follow-up samples and in the statistical analysis, important genetic associations may be missed. C1 [Lasky-Su, Jessica] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Lasky-Su, Jessica; Raby, Benjamin A.; Lazarus, Ross; Klanderman, Barbara; Silverman, Edwin K.; Celedon, Juan C.; Weiss, Scott T.; Lange, Christoph] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Heid, Iris M.; Vollmert, Caren; Illig, Thomas; Wichmann, H. -Erich] GSF, Natl Res Ctr Environm & Hlth, Inst Epidemiol, D-85764 Neuherberg, Germany. [Heid, Iris M.; Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, D-80539 Munich, Germany. [Emilsson, Valur; Thorleifsson, Gudmar] DeCode Genet, IS-101 Reykjavik, Iceland. [Lyon, Helen N.; Butler, Johannah; Hirschhorn, Joel] Childrens Hosp, Program Genom, Div Genet, Boston, MA 02115 USA. [Lyon, Helen N.; Butler, Johannah; Hirschhorn, Joel] Childrens Hosp, Program Genom, Div Endocrinol, Boston, MA 02115 USA. [Lyon, Helen N.; Butler, Johannah; Ardlie, Kristin; Hirschhorn, Joel] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Lyon, Helen N.; Butler, Johannah; Ardlie, Kristin; Hirschhorn, Joel] MIT, Cambridge, MA 02142 USA. [Lyon, Helen N.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Kronenberg, Florian] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, A-6020 Innsbruck, Austria. [Soto-Quiros, Manuel E.; Avila, Lydiana] Hosp Nacl Ninos Dr Carlos Saenz Herrera, Div Pediat Pulmonol, San Jose, Costa Rica. [Fox, Caroline S.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham, MA 01702 USA. [Fox, Caroline S.; Levy, Daniel; O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Laird, Nan; Ding, Xiao; Lange, Christoph] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [McQueen, Matt B.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Emilsson, Valur; Molony, Cliona; Schadt, Eric] Rosetta Inpharmat, Seattle, WA 98109 USA. [Hirschhorn, Joel] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Papoutsakis, Constantina; Dedoussis, George] Harokopio Univ, Dept Nutr & Dietet, Athens 17671, Greece. RP Lasky-Su, J (reprint author), SUNY Upstate Med Univ, Syracuse, NY 13210 USA. EM jessica.a.su@gmail.com; clange@hsph.harvard.edu RI Kronenberg, Florian/B-1736-2008; Genetic Epidemiology, Innsbruck Med.Univ./C-2095-2008; OI Kronenberg, Florian/0000-0003-2229-1120; lazarus, ross/0000-0003-3939-1961 FU NHLBI NIH HHS [HL04370, HL066289, K01 HL004370, N01-HC-25195, N01-HR-16044, N01-HR-16045, N01-HR-16046, N01-HR-16047, N01-HR-16048, N01-HR-16049, N01-HR-16050, N01-HR-16051, N01-HR-16052, N01HC25195, N01HR16044, P01 HL083069, P01HL083069, R01 HL066289, R37 HL066289, U01 HL065899, U01 HL65899]; NICHD NIH HHS [R01 HD060726] NR 33 TC 94 Z9 96 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2008 VL 82 IS 4 BP 849 EP 858 DI 10.1016/j.ajhg.2008.01.018 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 290DQ UT WOS:000255103900004 PM 18387595 ER PT J AU Assie, G LaFramboise, T Platzer, P Bertherat, J Stratakis, CA Eng, C AF Assie, Guillaume LaFramboise, Thomas Platzer, Petra Bertherat, Jerome Stratakis, Constantine A. Eng, Charis TI SNP Arrays in heterogeneous tissue: Highly accurate collection of both germline and somatic genetic information from unpaired single tumor samples SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ANALYSIS; NUCLEOTIDE POLYMORPHISM ARRAYS; ACUTE LYMPHOBLASTIC-LEUKEMIA; SQUAMOUS-CELL CARCINOMA; COPY NUMBER ALTERATION; UNIPARENTAL DISOMY; ALLELIC IMBALANCES; CHROMOSOMAL INSTABILITY; OLIGONUCLEOTIDE ARRAYS; GENOTYPING ARRAYS AB SNP arrays provide reliable genotypes and can detect chromosomal aberrations at a high resolution. However, tissue heterogeneity is currently a major limitation for somatic tissue analysis. We have developed SOMATICs, an original program for accurate analysis of heterogeneous tissue samples. Fifty-four samples (42 tumors and 12 normal tissues) were processed through Illumina Beadarrays and then analyzed with SOMATICs. We demonstrate that tissue heterogeneity-related limitations not only can be overcome but can also be turned into an advantage. First, admixture of normal cells with tumor can be used as an internal reference, thereby enabling highly sensitive detection of somatic deletions without having corresponding normal tissue. Second, the presence of normal cells allows for discrimination of somatic from germline aberrations, and the proportion of cells in the tissue sample that are harboring the somatic events can be assessed. Third, relatively early versus late somatic events can also be distinguished, assuming that late events occur only in subsets of cancer cells. Finally, admixture by normal cells allows inference of germline genotypes from a cancer sample. All this information can be obtained from any cancer sample containing a proportion of 40-75% of cancer cells. SOMATICs is a ready-to-use open-source program that integrates all of these features into a simple format, comprehensively describing each chromosomal event. C1 [Assie, Guillaume; LaFramboise, Thomas; Platzer, Petra; Eng, Charis] Cleveland Clin Fdn, Genom Med Inst, Lerner Res Inst, Cleveland, OH 44195 USA. [Eng, Charis] Cleveland Clin Fdn, Taussig Canc Inst, Cleveland, OH 44195 USA. [LaFramboise, Thomas; Eng, Charis] Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. [Eng, Charis] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. [Bertherat, Jerome] INSERM, U567, Inst Cochin, F-75014 Paris, France. [Bertherat, Jerome] Hop Cochin, Dept Endocrinol, F-75014 Paris, France. [Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Eng, C (reprint author), Cleveland Clin Fdn, Genom Med Inst, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM engc@ccf.org OI Eng, Charis/0000-0002-3693-5145 FU Intramural NIH HHS NR 41 TC 40 Z9 41 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2008 VL 82 IS 4 BP 903 EP 915 DI 10.1016/j.ajhg.2008.01.012 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 290DQ UT WOS:000255103900009 PM 18355774 ER PT J AU Antoniou, AC Spurdle, AB Sinilnikova, OM Healey, S Pooley, KA Schmutzler, RK Versmold, B Engel, C Meindl, A Arnold, N Hofmann, W Sutter, C Niederacher, D Deissler, H Caldes, T Kampjarvi, K Nevanlinna, H Simard, J Beesley, J Chen, XQ Neuhausen, SL Rebbeck, TR Wagner, T Lynch, HT Isaacs, C Weitzel, J Ganz, PA Daly, MB Tomlinson, G Olopade, OI Bium, JL Couch, FJ Peterlongo, P Manoukian, S Barile, M Radice, P Szabo, CI Pereira, LHM Greene, MH Rennert, G Leibkowicz, F Barnett-Griness, O Andrulis, IL Ozcelik, H Gerdes, AM Caligo, MA Laitman, Y Kaufman, B Milgrom, R Friedman, E Domchek, SM Nathanson, KL Osorio, A Llort, G Milne, RL Benitez, J Hamann, U Hogervorst, FBL Manders, P Ligtenberg, MJL van den Ouweland, AMW Peock, S Cook, M Platte, R Evans, DG Eeles, R Pichert, G Chu, C Eccles, D Davidson, R Douglas, F Godwin, AK Barjhoux, L Mazoyer, S Sobol, H Bourdon, V Eisinger, F Chompret, A Capoulade, C Paillerets, BBD Lenoir, GM Gauthier-Villars, M Houdayer, C Stoppa-Lyonnet, D Easton, DF AF Antoniou, Antonis C. Spurdle, Amanda B. Sinilnikova, Olga M. Healey, Sue Pooley, Karen A. Schmutzler, Rita K. Versmold, Beatrix Engel, Christoph Meindl, Alfons Arnold, Norbert Hofmann, Wera Sutter, Christian Niederacher, Dieter Deissler, Helmut Caldes, Trinidad Kampjarvi, Kati Nevanlinna, Heli Simard, Jacques Beesley, Jonathan Chen, Xiaoqing Neuhausen, Susan L. Rebbeck, Timothy R. Wagner, Theresa Lynch, Henry T. Isaacs, Claudine Weitzel, Jeffrey Ganz, Patricia A. Daly, Mary B. Tomlinson, Gail Olopade, Olufunmilayo I. Bium, Joanne L. Couch, Fergus J. Peterlongo, Paolo Manoukian, Siranoush Barile, Monica Radice, Paolo Szabo, Csilla I. Pereira, Lutecia H. Mateus Greene, Mark H. Rennert, Gad Leibkowicz, Flavio Barnett-Griness, Ofra Andrulis, Irene L. Ozcelik, Hilmi Gerdes, Anne-Marie Caligo, Maria A. Laitman, Yael Kaufman, Bella Milgrom, Roni Friedman, Eitan Domchek, Susan M. Nathanson, Katherine L. Osorio, Ana Llort, Gemma Milne, Roger L. Benitez, Javier Hamann, Ute Hogervorst, Frans B. L. Manders, Peggy Ligtenberg, Marjolijn J. L. van den Ouweland, Ans M. W. Peock, Susan Cook, Margaret Platte, Radka Evans, D. Gareth Eeles, Rosalind Pichert, Gabriella Chu, Carol Eccles, Diana Davidson, Rosemarie Douglas, Fiona Godwin, Andrew K. Barjhoux, Laure Mazoyer, Sylyie Sobol, Hagay Bourdon, Violaine Eisinger, Francois Chompret, Agnes Capoulade, Corinne Paillerets, Brigitte Bressac-de Lenoir, Gilbert M. Gauthier-Villars, Marion Houdayer, Claude Stoppa-Lyonnet, Dominique Easton, Douglas F. CA Kathleen Cuningharn Consortium Res OCGN Swedish BRCA1 DNA-HEBON Collaborators EMBRACE GEMO CIMBA TI Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PROPHYLACTIC OOPHORECTOMY; GENES; INVESTIGATORS; PENETRANCE; CONSORTIUM; MODIFIERS; MODEL AB Germline mutations in BRCA1 and BRCA2 confer high risks of breast cancer. However, evidence suggests that these risks are modified by other genetic or environmental factors that cluster in families. A recent genome-wide association study has shown that common alleles at single nucleotide polymorphisms (SNPs) in FGFR2 (rs2981582), TNRC9 (rs3803662), and MAP3K1 (rs889312) are associated with increased breast cancer risks in the general population. To investigate whether these loci are also associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers, we genotyped these SNPs in a sample of 10,358 mutation carriers from 23 studies. The minor alleles of SNP rs2981582 and rs889312 were each associated with increased breast cancer risk in BRCA2 mutation carriers (per-allele hazard ratio [HR] = 1.32, 95% CI: 1.20-1.45, p(trend) = 1.7 x 10(-8) and HR = 1.12, 95% CI: 1.02-1.24, P-trend = 0.02) but not in BRCA1 carriers. rs3803662 was associated with increased breast cancer risk in both BRCA1 and BRCA2 mutation carriers (per-allele HR = 1.13, 95% CI: 1.06-1.20, P-trend = 5 x 10(-5) in BRCA1 and BRCA2 combined). These loci appear to interact multiplicatively on breast cancer risk in BRCA2 mutation carriers. The differences in the effects of the FGFR2 and MAP3K1 SNPs between BRCA1 and BRCA2 carriers point to differences in the biology of BRCA1 and BRCA2 breast cancer tumors and confirm the distinct nature of breast cancer in BRCA1 mutation carriers. C1 [Antoniou, Antonis C.; Pooley, Karen A.; Peock, Susan; Cook, Margaret; Platte, Radka; DNA-HEBON Collaborators] Univ Cambridge, Dept Publ Hlth & Primary Care, Genet Epidemiol Unit, Canc Res UK, Cambridge CB2 1TN, England. [Spurdle, Amanda B.; Healey, Sue; Beesley, Jonathan; Chen, Xiaoqing] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Sinilnikova, Olga M.; Barjhoux, Laure] Hosp Civils Lyon, Ctr Leon Berard, Unite Mixte Genet Constitutionnelle Canc Frequent, Lyon, France. [Sinilnikova, Olga M.; Barjhoux, Laure; Mazoyer, Sylyie] Univ Lyon 1, CNRS, Lab Genet Mol Signalisat & Canc, UMR5201, F-69365 Lyon, France. [Pooley, Karen A.] Univ Cambridge, Dept Oncol, Human Canc Genet Grp, Canc Res UK, Cambridge CB2 1TN, England. [Schmutzler, Rita K.; Versmold, Beatrix] Univ Cologne, Div Mol Gynaecooncol, Dept Obstet & Gynaecol, D-5000 Cologne 41, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Arnold, Norbert] Univ Schleswig Holstein, Dept Obstet & Gynaecol, Kiel, Germany. [Hofmann, Wera] Charite Univ Med Ctr, Inst Human Genet, Berlin, Germany. [Sutter, Christian] Univ Heidelberg, Inst Human Genet, D-6900 Heidelberg, Germany. [Niederacher, Dieter] Univ Dusseldorf, Dept Obstet & Gynaecol, Mol Genet Lab, D-4000 Dusseldorf, Germany. [Deissler, Helmut] Univ Ulm, Dept Obstet & Gynaecol, D-89069 Ulm, Germany. [Caldes, Trinidad] Hosp Clin San Carlos, Madrid, Spain. [Kampjarvi, Kati; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynaecol, Helsinki, Finland. [Simard, Jacques] Univ Quebec, Ctr Hosp, Canc Genom Lab, Canada Res Chair Oncogenet, Ste Foy, PQ G1V 2M3, Canada. [Simard, Jacques] Univ Laval, Quebec City, PQ G1K 7P4, Canada. [Kathleen Cuningharn Consortium Res] Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia. [Neuhausen, Susan L.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Wagner, Theresa] Univ Vienna, Vienna, Austria. [Lynch, Henry T.] Creighton Univ, Omaha, NE 68178 USA. [Isaacs, Claudine] Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Fisher Ctr Familial Canc Res, Washington, DC USA. [Weitzel, Jeffrey] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Familial Canc Registry, Los Angeles, CA 90024 USA. [Daly, Mary B.; Godwin, Andrew K.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Tomlinson, Gail] Univ Texas Dallas, Dallas, TX 75230 USA. [Olopade, Olufunmilayo I.] Univ Chicago, Chicago, IL 60637 USA. [Bium, Joanne L.] Baylor Sammons Canc Ctr, Dallas, TX USA. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Peterlongo, Paolo; Radice, Paolo] Ist Nazl Tumori, Fdn IRCCS, Dept Expt Oncol, Unit Genet Susceptibil Canc, I-20133 Milan, Italy. [Manoukian, Siranoush] Fdn Ist FIRC Oncol Med, Med Genet Serv, Milan, Italy. [Barile, Monica] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy. [Szabo, Csilla I.] Mayo Clin, Coll Med, Dept Lab Med & Expt Pathol, Rochester, MN USA. [Pereira, Lutecia H. Mateus] US NCI, Lab Populat Genet, NIH, Rockville, MD USA. [Greene, Mark H.] NCI, Clin Genet Branch, Rockville, MD USA. [Rennert, Gad; Leibkowicz, Flavio; Barnett-Griness, Ofra] CHS Natl Canc Control Ctr, Haifa, Israel. [Rennert, Gad; Leibkowicz, Flavio; Barnett-Griness, Ofra] Carmel Med Ctr & B Rappaport, Fac Med, Dept Commun Med & Epidemiol, Haifa, Israel. [Andrulis, Irene L.; OCGN] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.; OCGN] Ontario Canc Genet Network, Canc Care Ontario, Toronto, ON, Canada. [Andrulis, Irene L.; Ozcelik, Hilmi] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.; Ozcelik, Hilmi] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Gerdes, Anne-Marie] Odense Univ Hosp, Dept Biochem Pharmacol & Genet, Odense, Denmark. [Caligo, Maria A.] Univ Pisa, Dept Oncol, Div Surg Mol & Ultrastruct, Pisa, Italy. [Caligo, Maria A.] Pisa Univ Hosp, Pisa, Italy. [Laitman, Yael; Milgrom, Roni; Friedman, Eitan] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella; Friedman, Eitan] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel. [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Sch Med, Dept Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Ctr, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Llort, Gemma] Inst Catala Oncol, Genet Counselling Unit, Prevent & Canc Control Ser, Barcelona, Spain. [Milne, Roger L.; Benitez, Javier] Spanish Natl Canc Ctr, Human Canc Genet Programme, Genotyping Unit, Madrid, Spain. [Hamann, Ute] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Dept Pathol, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands. [Manders, Peggy] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Ligtenberg, Marjolijn J. L.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Ligtenberg, Marjolijn J. L.] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands. [van den Ouweland, Ans M. W.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Evans, D. Gareth] St Marys Hosp, Acad Unit Med Genet, Manchester M13 0JH, Lancs, England. [Evans, D. Gareth] St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. [Eeles, Rosalind] Inst Canc Res, Translat Canc Genet Team, New York, NY USA. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London, England. [Pichert, Gabriella] Guys Hosp, London, England. [Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Davidson, Rosemarie] Ferguson Smith Ctr Clin Geneet, Glasgow, Lanark, Scotland. [Douglas, Fiona] Inst Human Genet, Ctr Life, Newcastle Upon Tyne, Tyne & Wear, England. [Sobol, Hagay; Bourdon, Violaine; Eisinger, Francois] Inst J Paoli I Calmettes, INSERM UMR599, Dept Oncol Genet, F-13275 Marseille, France. [Chompret, Agnes] Inst Gustave Roussy, Dept Med, Villejuif, France. [Capoulade, Corinne; Paillerets, Brigitte Bressac-de; Lenoir, Gilbert M.] Inst Gustave Roussy, Dept Genet, CNRS FRE2939, Villejuif, France. [Gauthier-Villars, Marion; Houdayer, Claude; Stoppa-Lyonnet, Dominique] Univ Paris 05, Dept Genet, Inst Curie, Paris, France. RP Antoniou, AC (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Genet Epidemiol Unit, Canc Res UK, Cambridge CB2 1TN, England. EM antonis@srl.cam.ac.uk RI Spurdle, Amanda/A-4978-2011; Arnold, Norbert/E-3012-2010; Andrulis, Irene/E-7267-2013; Radice, Paolo/O-3119-2013; Osorio, Ana/I-4324-2014; Manders, P./L-4501-2015; Ligtenberg, Marjolijn/N-9666-2013; manoukian, siranoush/E-7132-2017; OI Spurdle, Amanda/0000-0003-1337-7897; Arnold, Norbert/0000-0003-4523-8808; Osorio, Ana/0000-0001-8124-3984; Ligtenberg, Marjolijn/0000-0003-1290-1474; manoukian, siranoush/0000-0002-6034-7562; Nathanson, Katherine/0000-0002-6740-0901; Eeles, Rosalind/0000-0002-3698-6241; Nevanlinna, Heli/0000-0002-0916-2976; Evans, Gareth/0000-0002-8482-5784 FU Cancer Research UK [, 10118]; NCI NIH HHS [R01-CA74415, 1U01 CA 86389, 5U01 CA113916, CA122340, N02-CP-11019-50, N02CP11019, N02CP65504, P-50 CA 83638, P30 CA051008, P30 CA51008-12, P50 CA083638, P50 CA116201, P50-CA116201, R01 CA074415, R01 CA083855, R01 CA102776, R01 CA122340, R01-CA083855, R01-CA102776, RC4 CA153828, U01 CA069631, U01 CA086389, U01 CA086389-09, U01 CA113916, U01 CA69631]; NCRR NIH HHS [M01 RR000043, M01 RR00043]; Associazione Italiana per la Ricerca sul Cancro NR 20 TC 177 Z9 184 U1 1 U2 32 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2008 VL 82 IS 4 BP 937 EP 948 DI 10.1016/j.ajhg.2008.02.008 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 290DQ UT WOS:000255103900012 PM 18355772 ER PT J AU Bergmann, C Fliegauf, M Bruchle, NO Frank, V Olbrich, H Kirschner, J Schermer, B Schmedding, I Kispert, A Kranzlin, B Nurnberg, G Becker, C Grimm, T Girschick, G Lynch, SA Kelehan, P Senderek, J Neuhaus, TJ Stallmach, T Zentgraf, H Nurnberg, P Gretz, N Lo, C Lienkamp, S Schafer, T Walz, G Benzing, T Zerres, K Omran, H AF Bergmann, Carsten Fliegauf, Manfred Bruechle, Nadina Ortiz Frank, Valeska Olbrich, Heike Kirschner, Jan Schermer, Bernhard Schmedding, Ingolf Kispert, Andreas Kraenzlin, Bettina Nuernberg, Gudrun Becker, Christian Grimm, Tiemo Girschick, Gundula Lynch, Sally A. Kelehan, Peter Senderek, Jan Neuhaus, Thomas J. Stallmach, Thomas Zentgraf, Hanswalter Nuernberg, Peter Gretz, Norbert Lo, Cecilia Lienkamp, Soeren Schaefer, Tobias Walz, Gerd Benzing, Thomas Zerres, Klaus Omran, Heymut TI Loss of nephrocystin-3 function can cause embryonic lethality, meckel-gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; BARDET-BIEDL-SYNDROME; RIGHT AXIS DETERMINATION; BASAL BODY PROTEIN; JOUBERT-SYNDROME; PRIMARY CILIA; ADOLESCENT NEPHRONOPHTHISIS; SYNDROME GENE; PCY MICE; MUTATIONS AB Many genetic diseases have been linked to the dysfunction of primary cilia, which occur nearly ubiquitously in the body and act as solitary cellular mechanosensory organelles. The list of clinical manifestations and affected tissues in cilia-related disorders (ciliopathies) such as nephronophthisis is broad and has been attributed to the wide expression pattern of ciliary proteins. However, little is known about the molecular mechanisms leading to this dramatic diversity of phenotypes. We recently reported hypomorpoic NPHP3 mutations in children and young adults with isolated nephronophthisis and associated hepatic fibrosis or tapetoretinal degeneration. Here, we chose a combinatorial approach in mice and humans to define the phenotypic spectrum of NPHP3/Nphp3 mutations and the role of the nephrocystin-3 protein. We demonstrate that the pcy mutation generates a hypomorphic Nphp3 allele that is responsible for the cystic kidney disease phenotype, whereas complete loss of Nphp3 function results in situs inversus, congenital heart defects, and embryonic lethality in mice. In humans, we show that NPHP3 mutations can cause a broad clinical spectrum of early embryonic patterning defects comprising situs inversus, polydactyly, central nervous system malformations, structural heart defects, preauricular fistulas, and a wide range of congenital anomalies of the kidney and urinary tract (CAKUT). On the functional level, we show that nephrocystin-3 directly interacts with inversin and can inhibit like inversin canonical Writ signaling, whereas nephrocystin-3 deficiency leads in Xenopus laevis to typical planar cell polarity defects, suggesting a role in the control of canonical and noncanonical (planar cell polarity) Writ signaling. C1 [Bergmann, Carsten; Bruechle, Nadina Ortiz; Frank, Valeska; Zerres, Klaus] Rhein Westfal TH Aachen, Dept Human Genet, D-52074 Aachen, Germany. [Fliegauf, Manfred; Olbrich, Heike; Kirschner, Jan; Omran, Heymut] Univ Freiburg, Med Ctr, Dept Pediat & Adolescent Med, D-79106 Freiburg, Germany. [Schermer, Bernhard; Schmedding, Ingolf; Benzing, Thomas] Univ Cologne, Dept Med 4, D-50924 Cologne, Germany. [Schermer, Bernhard; Schmedding, Ingolf; Benzing, Thomas] Univ Cologne, Kidney Res Ctr Cologne, D-50924 Cologne, Germany. [Kispert, Andreas] Hannover Med Sch, Inst Mol Biol, D-30625 Hannover, Germany. [Kraenzlin, Bettina; Gretz, Norbert] Univ Heidelberg, Klinikum Mannheim, Med Res Ctr, D-68167 Mannheim, Germany. [Nuernberg, Gudrun; Becker, Christian; Nuernberg, Peter] Univ Cologne, Cologne Ctr Genom, D-50674 Cologne, Germany. [Nuernberg, Gudrun; Becker, Christian] RZPD Deutsch Ressourcenzentrum Genomforsch Gmbh, D-13125 Berlin, Germany. [Grimm, Tiemo] Univ Wurzburg, Dept Human Genet, D-97074 Wurzburg, Germany. [Nuernberg, Gudrun] Univ Wurzburg, Dept Obstet & Gynecol, D-97080 Wurzburg, Germany. [Lynch, Sally A.] Our Ladys Hosp Sick Children, Natl Ctr Med Genet, Dublin 12, Ireland. [Kelehan, Peter] Natl Matern Hosp, Dept Histopathol, Dublin 2, Ireland. [Neuhaus, Thomas J.] Univ Zurich, Childrens Hosp, Nephrol Unit, CH-8032 Zurich, Switzerland. [Stallmach, Thomas] Univ Zurich, Dept Pathol, CH-8091 Zurich, Switzerland. [Zentgraf, Hanswalter] Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany. [Nuernberg, Peter] Univ Cologne, Inst Genet, D-50674 Cologne, Germany. [Lo, Cecilia] NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Lienkamp, Soeren; Schaefer, Tobias; Walz, Gerd] Univ Hosp Freiburg, Div Renal, D-79106 Freiburg, Germany. RP Bergmann, C (reprint author), Rhein Westfal TH Aachen, Dept Human Genet, D-52074 Aachen, Germany. EM cbergmann@ukaachen.de RI Senderek, Jan/F-8405-2015; Schermer, Bernhard/E-9972-2014; Kirschner, Janbernd/H-7418-2016 OI Senderek, Jan/0000-0002-8263-1783; Schermer, Bernhard/0000-0002-5194-9000; Kirschner, Janbernd/0000-0003-1618-7386 NR 37 TC 145 Z9 155 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2008 VL 82 IS 4 BP 959 EP 970 DI 10.1016/j.ajhg.2008.02.017 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 290DQ UT WOS:000255103900014 PM 18371931 ER PT J AU Waterman, AD Browne, T Waterman, BM Gladstone, EH Hostetter, T AF Waterman, Amy D. Browne, Teri Waterman, Brian M. Gladstone, Elisa H. Hostetter, Thomas TI Attitudes and behaviors of African Americans regarding early detection of kidney disease SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE African American; kidney disease; knowledge; risk factors; hypertension; diabetes; family history; prevention; early detection; end-stage renal disease; attitudes ID PATIENT EDUCATION; RENAL-FAILURE; HYPERTENSION; OUTCOMES; RISK; POPULATION; AWARENESS; PROGRAMS; BENEFITS; HEALTH AB Background: Chronic kidney disease (CKD) is an African American public health crisis. To inform interventions, the National Kidney Disease Education Program surveyed African Americans about their attitudes and behaviors regarding early detection of kidney disease and screening. Study Design: Cross-sectional study. Setting & Participants: 2,017 African Americans from 7 states (Georgia, Maryland, Ohio, Mississippi, Louisiana, Missouri, and Tennessee) selected by using a random-digit dialing telephone survey (response rate, 42.4%). Predictors: Demographic, risk, knowledge, and behavior variables. Outcomes & Measurements: Perception of CKD as a top health concern, perceived risk of getting kidney disease, and accurate knowledge about CKD and its prevention. Results: Only 23.5% of African Americans were screened for kidney disease in the last year. Although almost half (43.7%) of African Americans had a CKD risk factor, only 2.8% reported that CKD was a top health concern. Almost half knew the correct definition of kidney disease (48.6%), but few knew a test to diagnose CKD (23.7%) or that African Americans were at greater risk of developing CKD (18.1 %). African Americans who had diabetes (odds ratio [OR], 3.22; 95% confidence interval [CI], 2.17 to 4.76), hypertension (OR, 1.78; 95% CI, 1.28 to 2.44), at least a bachelor's degree (OR, 1.77; 95% CI, 1.17 to 2.66), who had spoken with a medical professional (OR, 1.85; 95% CI, 1.19 to 2.85) or their family (OR, 1.61; 95% CI, 1.11 to 2.38) about kidney disease, who knew that a family history of kidney disease is a risk factor (OR, 2.32; 95% CI, 1.08 to 5.0), and who had been tested for CKD in the last year (OR, 1.45; 95% CI, 1.03 to 2.0) were more likely to correctly perceive themselves at increased risk. Limitations: Respondents were primarily African American women from urban areas. Conclusions: Most African Americans have poor knowledge about CKD, do not perceive it as an important health problem, and are not getting screened. To increase early detection of kidney disease through screenings, educational efforts linking kidney disease prevention to other diseases that are health priorities for African Americans are necessary. C1 [Waterman, Amy D.] Washington Univ, Sch Med, Div Gen Med Sci, St Louis, MO 63110 USA. [Browne, Teri] Univ Chicago, Sch Social Serv Adm, Chicago, IL 60637 USA. [Waterman, Brian M.] Waterman Res Soult, St Louis, MO USA. [Gladstone, Elisa H.] NIH, Natl Kidney Dis Educ Program, Bethesda, MD 20892 USA. [Hostetter, Thomas] Albert Einstein Coll Med, Dept Med, Div Nephrol, Bronx, NY 10467 USA. RP Waterman, AD (reprint author), Washington Univ, Sch Med, Div Gen Med Sci, Campus Box 8005,600 S Euclid, St Louis, MO 63110 USA. EM awaterma@im.wustl.edu RI Browne, Teri/E-2186-2011; OI Waterman, Amy/0000-0002-7799-0060 FU NIDDK NIH HHS [1 K01 DK066239-01] NR 32 TC 29 Z9 30 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2008 VL 51 IS 4 BP 554 EP 562 DI 10.1053/j.ajkd.2007.12.020 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 286VP UT WOS:000254874400006 PM 18371531 ER PT J AU Ward, MM AF Ward, Michael M. TI Socioeconomic status and the incidence of ESRD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE socioeconomic status; health disparities; end-stage renal disease; diabetes mellitus; systemic lupus erythematosus; autosomal dominant polycystic kidney disease ID STAGE RENAL-DISEASE; POLYCYSTIC KIDNEY-DISEASE; FACTOR INTERVENTION TRIAL; DIABETES COMPLICATIONS; GLYCEMIC CONTROL; LUPUS NEPHRITIS; ATHEROSCLEROSIS RISK; INTENSIVE TREATMENT; MORTALITY RISK; UNITED-STATES AB Background: Persons of low socioeconomic status (SES) may be at increased risk of end-stage renal disease (ESRD). This study examines the association between SES and incidence of ESRD caused by all primary renal diseases and caused by 3 diseases that differ in the availability of effective treatment: diabetes mellitus, lupus nephritis, and autosomal dominant polycystic kidney disease (ADPKD). Study Design: Retrospective cohort study. Setting & Participants: Adults with incident ESRD in the United States from January 1, 1996, to June 30, 2004 (N = 747,556). Predictor: SES, based on characteristics of the patient's ZIP code of residence. Outcomes: Incidence of ESRD. Results: In all sex-race groups, the incidence of ESRD caused by all primary renal diseases was greatest in those in the lowest SES score quartile and decreased progressively with higher SES. For example, for white women, the incidence of ESRD was 388.9 per million in the lowest quartile of SES and 200.8 per million in the highest quartile of SES (relative risk, 1.92; 95% confidence interval, 1.89 to 1.95). However, this association differed among patients with primary renal diseases. There were strong associations between SES and ESRD caused by diabetes mellitus, weaker associations for ESRD caused by lupus nephritis, and generally no associations for ESRD caused by ADPKD. For example, for white women, relative risks of ESRD in the lowest compared with the highest SES quartile were 2.84 for ESRD caused by diabetes mellitus, 1.63 for ESRD caused by lupus nephritis, and 1.27 for ESRD caused by ADPKD. Limitations: Use of an area-based measure of SES. Conclusions: The strength of the association between SES and ESRD differs among patients with diabetes mellitus, lupus nephritis, and ADPKD, suggesting that socioeconomic factors act differently in the progression of chronic kidney disease in these conditions. C1 NIH, NIAMS, Intramural Res Program, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIH, NIAMS, Intramural Res Program, Bldg 10 CRC,Rm 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov NR 55 TC 59 Z9 60 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2008 VL 51 IS 4 BP 563 EP 572 DI 10.1053/j.ajkd.2007.11.023 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 286VP UT WOS:000254874400007 PM 18371532 ER PT J AU Agodoa, LY Francis, ME Eggers, PW AF Agodoa, Lawrence Y. Francis, Mildred E. Eggers, Paul W. TI Association of analgesic use with prevalence of albuminuria and reduced GFR in US adults SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE analgesics use; decreased kidney function; NHANES 1999-2002 ID CHRONIC KIDNEY-DISEASE; CHRONIC RENAL-DISEASE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NONNARCOTIC ANALGESICS; SERUM CREATININE; URINARY ALBUMIN; UNITED-STATES; RISK; NEPHROPATHY; ACETAMINOPHEN AB Background: Prolonged analgesic consumption may adversely affect kidney function. The relation of long-term analgesic use to markers of decreased kidney function has not been investigated in the general population. Design: Cross-sectional analysis. Setting: National Health and Nutrition Examination Survey conducted in 1999-2002. Participants: Noninstitutionalized residents at least 20 years old (n = 8,057, representing 177.8 million adults). Predictors: Ever intake of an analgesic every day for at least a month defined habitual analgesic use, classified by product (aspirin, acetaminophen, ibuprofen, and selected prescription drugs) and years of use (< 1, 1 to 5, and > 5 years). Outcomes: Albuminuria in random urine (albumin-creatinine ratio >= 30 mg/g; n = 1,088) and reduced estimated glomerular filtration rate (eGFR; < 60 mL/min/1.73 m(2), n = 852) using the Modification of Diet in Renal Disease Study equation and the composite of either. Measurements: Age-standardized prevalence in habitual analgesic users and non-habitual analgesic users and multivariable-adjusted odds ratios (ORs). Results: In US adults, 23.7% (95% confidence interval [CI], 21.7 to 25.6) reported habitual analgesic use. Multivariable-adjusted ORs for reduced eGFR prevalence in adults with habitual analgesic use of acetaminophen only, ibuprofen only, and aspirin only were 1.03 (95% CI, 0.6 to 1.7),1.21 (95% CI, 0.7 to 2.1), and 0.95 (95% CI, 0.7 to 1.2) compared with non-habitual analgesic use, respectively, Corresponding ORs for prevalent albuminuria were 0.93 (95% CI, 0.7 to 1.3), 0.65 (95% CI, 0.4 to 1.2), and 0.86 (95% CI, 0.6 to 1.2). Association measures had intermediate levels for the composite marker of decreased kidney function and were not significant. No association between prevalent outcomes and habitual analgesic exposure duration of 5 years or longer or multiple product habitual analgesic consumption was observed. Limitations: Reliability of self-reported analgesic use behavior was not assessed. Conclusions: Habitual analgesic use of single or multiple products was not associated with increased prevalence of albuminuria or reduced eGFR. C1 [Agodoa, Lawrence Y.; Eggers, Paul W.] NIDDK, Div Kidney Urol & Hematol Disorders, Bethesda, MD 20892 USA. [Francis, Mildred E.] Social & Sci Syst Inc, Silver Spring, MD USA. RP Agodoa, LY (reprint author), NIDDK, Div Kidney Urol & Hematol Disorders, 6707 Democracy Blvd,Rm 611, Bethesda, MD 20892 USA. EM agodoal@extra.niddk.nih.gov FU NIDDK NIH HHS [N001-DK-1-2478] NR 37 TC 12 Z9 12 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2008 VL 51 IS 4 BP 573 EP 583 DI 10.1053/j.ajkd.2007.12.014 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 286VP UT WOS:000254874400008 PM 18371533 ER PT J AU Shang, H Lim, J Ju, W Kopp, JB Hostetter, TH Angeletti, RH Bitzer, M AF Shang, H. Lim, J. Ju, W. Kopp, J. B. Hostetter, T. H. Angeletti, R. H. Bitzer, M. TI Urinary markers for progressive renal fibrosis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY APR 02-06, 2008 CL Dallas, TX SP Natl Kidney Fdn C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Mt Sinai Sch Med, New York, NY USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2008 VL 51 IS 4 MA 29 BP A35 EP A35 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 286VP UT WOS:000254874400056 ER PT J AU Muntner, P Winston, J Uribarri, J Mann, D Fox, CS AF Muntner, Paul Winston, Jonathan Uribarri, Jaime Mann, Devin Fox, Caroline S. TI Overweight, obesity, and elevated serum cystatin C levels in adults in the United States SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE body mass index; kidney disease; overweight ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; BODY-MASS INDEX; RISK; METAANALYSIS; CREATININE; POPULATION; PREDICTORS; REDUCTION AB BACKGROUND: Although high body mass index (BMI) is a risk factor for hypertension, diabetes, and cardiovascular disease, limited data exist on the association of overweight and obesity with early stages of kidney disease. METHODS: Cross-sectional data for 5083 participants of the nationally representative Third National Health and Nutrition Examination Survey with an estimated glomerular filtration rate >= 60 mL/min/1.73 m(2) without micro- or macroalbuminuria were analyzed to determine the association between BMI and elevated serum cystatin C. Normal weight, overweight, class I obesity, and class II to III obesity were defined as a BMI of 18.5 to 24.9 kg/m(2), 25.0 to 29.9 kg/m(2), 30.0 to 34.9 kg/m(2), and >= 35.0 kg/m(2), respectively. Elevated serum cystatin C was defined as >= 1.09 mg/L (>= 99th percentile for participants 20-39 years of age without diabetes, hypertension, micro-or macroalbuminuria, or stage 3-5 chronic kidney disease). RESULTS: The age-standardized prevalence of elevated serum cystatin C was 9.6%, 12.9%, 17.4%, and 21.5% among adults of normal weight, overweight, class I obesity, and class II to III obesity, respectively (P trend < .001). After multivariate adjustment for demographics, behaviors, systolic blood pressure, and serum biomarkers, and compared with participants of normal weight, the odds ratio (95% confidence interval) of elevated serum cystatin C was 1.46 (1.02-2.10) for overweight, 2.36 (1.56-3.57) for class I obesity, and 2.82 (1.56-5.11) for class II to III obesity. CONCLUSION: A graded association exists between higher BMI and elevated serum cystatin C. Further research is warranted to assess whether reducing BMI favorably affects elevated serum cystatin C and the development of chronic kidney disease. (C) 2008 Elsevier Inc. All rights reserved. C1 Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. [Winston, Jonathan; Uribarri, Jaime; Mann, Devin] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Muntner, P (reprint author), Mt Sinai Sch Med, Dept Community & Prevent Med, 1 Gustave L Levy Pl,Box 1057, New York, NY 10029 USA. EM paul.muntner@mssm.edu OI Mann, Devin/0000-0002-2099-0852 FU NHLBI NIH HHS [N01 HC025195] NR 25 TC 65 Z9 67 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 APR PY 2008 VL 121 IS 4 BP 341 EP 348 DI 10.1016/j.amjmed.2008.01.003 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 280JV UT WOS:000254423700017 PM 18374694 ER PT J AU Chen, KT Tuomala, RE Chu, C Huang, ML Watts, DH Zorrilla, CD Paul, M Hershow, R Larussa, P AF Chen, Katherine T. Tuomala, Ruth E. Chu, Clara Huang, Meei-Li Watts, D. Heather Zorrilla, Carmen D. Paul, Mary Hershow, Ron Larussa, Philip TI No association between antepartum serologic and genital tract evidence of herpes simplex virus-2 coinfection and perinatal HIV-1 transmission SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE herpes simplex virus 2 infection; perinatal HIV-1; transmission; pregnancy; transmitted infection ID HUMAN-IMMUNODEFICIENCY-VIRUS; PREGNANT-WOMEN; UNITED-STATES; TYPE-1 RNA; INFECTION; RISK; DNA; REACTIVATION; ACQUISITION; THERAPY AB OBJECTIVE: The purpose of this study was to assess the risk of perinatal HIV-1 transmission in women who are coinfected with herpes simplex virus-2 (HSV-2). STUDY DESIGN: We performed a nested case-control study of 26 women whose HIV-1 was transmitted to their infants and 52 control subjects whose HIV-1 was not transmitted. We assessed antepartum serologic evidence of HSV-2 by HSV-2 serostatus and genital tract evidence of HSV-2 by presence of HSV-2 DNA. RESULTS: There was no significant association between antepartum serologic evidence of HSV-2 coinfection and the risk of perinatal HIV-1 transmission. There was also no association between antepartum genital tract evidence of HSV-2 coinfection and risk of perinatal HIV-1 transmission. CONCLUSION: Women who were infected with HIV-1 with antepartum serologic and genital tract evidence of HSV-2 coinfection did not appear to have an increased risk of perinatal HIV-1 transmission. However, further investigations are needed to assess HSV-2 reactivation and the risk of perinatal HIV-1 transmission at the time of delivery. C1 [Chen, Katherine T.] Columbia Univ, Dept Obstet & Gynecol & Epidemiol, New York, NY 10032 USA. [Larussa, Philip] Columbia Univ, Dept Pediat, New York, NY 10032 USA. [Tuomala, Ruth E.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Huang, Meei-Li] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Chu, Clara] Clin Trials & Surveys Corp, Baltimore, MD USA. [Watts, D. Heather] NICHHD, Pediat Adolescent & Maternal Acquired Immunodefic, Bethesda, MD 20892 USA. [Zorrilla, Carmen D.] Univ Puerto Rico, Sch Med, Dept Obstet & Gynecol, San Juan, PR 00936 USA. [Paul, Mary] Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. [Paul, Mary] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Hershow, Ron] Univ Illinois, Dept Internal Med, Chicago, IL USA. RP Chen, KT (reprint author), Columbia Univ, Dept Obstet & Gynecol & Epidemiol, 722 W 168th St, New York, NY 10032 USA. EM ktc10@columbia.edu FU NCRR NIH HHS [RR000188, RR000645]; NIAID NIH HHS [U01 AI 034841, 1 U01 AI 050274-01, N01 AI 085339, U01 AI 034858]; NICHD NIH HHS [SK12 HD01275, U01 HD 036117, U01 HD 041983]; NIDA NIH HHS [U01 DA 015053, 9U01 DA 015054] NR 28 TC 1 Z9 1 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 APR PY 2008 VL 198 IS 4 AR 399.e1 DI 10.1016/j.ajog.2007.10.784 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 288IR UT WOS:000254980200017 PM 18177832 ER PT J AU Kusanovic, JP Romero, R Espinoza, J Nien, JK Kim, CJ Mittal, P Edwin, S Erez, O Gotsch, F Mazaki-Tovi, S Than, NG Soto, E Camacho, N Gomez, R Quintero, R Hassan, SS AF Kusanovic, Juan Pedro Romero, Roberto Espinoza, Jimmy Nien, Jyh Kae Kim, Chong Jai Mittal, Pooja Edwin, Sam Erez, Offer Gotsch, Francesca Mazaki-Tovi, Shali Than, Nandor G. Soto, Eleazar Camacho, Natalia Gomez, Ricardo Quintero, Ruben Hassan, Sonia S. TI Twin-to-twin transfusion syndrome: an antiangiogenic state? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper 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 DE angiogenesis; angiogenic factors; birthweight discordancy; endoglin; monochorionic; placental growth factor; PIGF; sFIt1; sVEGFR-1; TTTS; twin pregnancy ID ENDOTHELIAL GROWTH-FACTOR; CIRCULATING ANGIOGENIC FACTORS; HUMAN FETOPLACENTAL VASCULOGENESIS; MONOCHORIONIC DIAMNIOTIC TWINS; VELAMENTOUS CORD INSERTION; HEALTHY NULLIPAROUS WOMEN; BIRTH-WEIGHT DISCORDANCY; AMNIOTIC-FLUID VOLUME; FACTOR RECEPTOR-1; TYROSINE KINASE-1 AB OBJECTIVE: An imbalanced chronic blood flow between the donor and recipient twin through placental vascular anastomoses is the accepted pathophysiology of twin-to-twin transfusion syndrome (TTTS). Vascular endothelial growth factor receptor-1 (VEGFR-1) mRNA is overexpressed only in the syncytiotrophoblast of the donor twin in some cases of TTTS. This study was conducted to determine maternal plasma concentrations of placental growth factor (PIGF), soluble VEGFR-1, and soluble endoglin (s-Eng) in monochorionic-diamniotic pregnancies with and without TTTS. STUDY DESIGN: This case-control study included monochorionic-diamniotic pregnancies between 16-26 weeks with and without TTTS. Maternal plasma concentrations of PlGF, sVEGFR-1, and s-Eng were determined with ELISA. A P value <.05 was considered statistically significant. RESULTS: Patients with TTTS had higher median plasma concentrations of s-Eng (14.8 ng/mL vs 7.8 ng/mL; P <.001) and sVEGFR-1 (6383.1 pg/mL vs 3220.1 pg/mL; P <.001]; and lower median plasma concentrations of PlGF (115.5 pg/mL vs 359.3 pg/mL; P =.002) than those without TTTS. CONCLUSION: We propose that an antiangiogenic state may be present in some cases of TTTS. C1 [Kusanovic, Juan Pedro; Romero, Roberto; Espinoza, Jimmy; Kim, Chong Jai; Mittal, Pooja; Edwin, Sam; Erez, Offer; Gotsch, Francesca; Than, Nandor G.; Camacho, Natalia; Hassan, Sonia S.] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Kusanovic, Juan Pedro; Romero, Roberto; Espinoza, Jimmy; Kim, Chong Jai; Mittal, Pooja; Edwin, Sam; Erez, Offer; Gotsch, Francesca; Than, Nandor G.; Camacho, Natalia; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Kusanovic, Juan Pedro; Espinoza, Jimmy; Mittal, Pooja; Mazaki-Tovi, Shali; Soto, Eleazar; Camacho, Natalia; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. [Nien, Jyh Kae; Gomez, Ricardo] Pontificia Univ Catolica Chile, Sotero Rio Hosp, CEDIP, Puente Alto, Chile. [Quintero, Ruben] Univ S Florida, Dept Obstet & Gynecol, Tampa, FL 33620 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu NR 93 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 APR PY 2008 VL 198 IS 4 AR 382.e1 DI 10.1016/j.ajog.2008.02.016 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 288IR UT WOS:000254980200010 ER PT J AU Leach, RE Kilburn, BA Petkova, A Romero, R Armant, R AF Leach, Richard E. Kilburn, Brian A. Petkova, Anelia Romero, Roberto Armant, Randall TI Diminished survival of human cytotrophoblast cells exposed to hypoxia/reoxygenation injury and associated reduction of heparin-binding epidermal growth factor-like growth factor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the American-Gynecological-and-Obstetrical-Society CY SEP 26-29, 2007 CL Chicago, IL SP Amer Gynecol & Obstet Soc DE apoptosis; cytotrophoblast; epidermal growth factor receptor; heparin-binding epithelial growth factor-like growth factor; human epidermal receptor 4; hypoxia; hypoxia/reoxygenation ID PLACENTAL OXIDATIVE STRESS; RENAL EPITHELIAL-CELLS; INTESTINAL ISCHEMIA/REPERFUSION INJURY; ISCHEMIA-REPERFUSION INJURY; EARLY-PREGNANCY FAILURE; IN-VITRO; TROPHOBLAST SURVIVAL; HB-EGF; PREECLAMPSIA; HYPOXIA AB OBJECTIVE: The antiapoptotic action of heparin-binding epidermal growth factor (HBEGF)-like growth factor and its regulation by O-2 constitutes a key factor for trophoblast survival. The hypothesis that cytotrophoblast survival is compromised by exposure to hypoxia-reoxygenation (H/R) injury, which may contribute to preeclampsia and some missed abortions, prompted us to investigate HBEGF regulation and its role as a survival factor during H/R in cytotrophoblast cells. STUDY DESIGN: A transformed human first-trimester cytotrophoblast cell line HTR-8/SVneo was exposed to H/R (2% O-2 followed by 20% O2) and assessed for HBEGF expression and cell death. RESULTS: Cellular HBEGF declined significantly within 30 minutes of reoxygenation after culture at 2% O2. H/R significantly reduced proliferationand increased cell death when compared with trophoblast cells cultured continuously at 2% or 20% O-2. Restoration of cell survival also was achieved by adding recombinant HBEGF during reoxygenation. HBEGF inhibited apoptosis through its binding to either human epidermal receptor (HER)-1 or HER4, its cognate receptors. CONCLUSION: These results provide evidence that cytotrophoblast exposure to H/R induces apoptosis and decreased cell proliferation. HBEGF accumulation is diminished under these conditions, whereas restoration of HBEGF signaling improves trophoblast survival. C1 [Leach, Richard E.] Univ Illinois, Sch Med, Dept Obstet & Gynecol, Chicago, IL USA. [Leach, Richard E.] Univ Illinois, Sch Med, Dept Physiol & Biophys, Chicago, IL USA. [Kilburn, Brian A.; Petkova, Anelia; Armant, Randall] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Detroit, MI USA. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Armant, Randall] Wayne State Univ, Dept Anat, Detroit, MI USA. [Armant, Randall] Wayne State Univ, Dept Cell Biol, Detroit, MI USA. [Armant, Randall] NICHHD, Reprod Biol & Med Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Leach, RE (reprint author), Michigan State Univ, Coll Human Med, Dept Obstet Gynecol & Reprod Biol, 234 Div N,4th Floor, Grand Rapids, MI 49503 USA. EM richard.leach@hc.msu.edu OI Armant, D. Randall/0000-0001-5904-9325 FU Intramural NIH HHS [Z99 HD999999]; NIAAA NIH HHS [AA12057]; NICHD NIH HHS [R01 HD037500, R01 HD037500-05, U54 HD040093-060003, HD37500] NR 32 TC 4 Z9 6 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2008 VL 198 IS 4 AR 471.e1 DI 10.1016/j.ajog.2008.01.009 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 288IR UT WOS:000254980200060 PM 18395045 ER PT J AU Rogers, R Norian, J Malik, M Christman, G Abu-Asab, M Chen, F Korecki, C Iatridis, J Catherino, WH Tuan, RS Dhillon, N Leppert, P Segars, JH AF Rogers, Rebecca Norian, John Malik, Minnie Christman, Gregory Abu-Asab, Mones Chen, Faye Korecki, Casey Iatridis, James Catherino, William H. Tuan, Rocky S. Dhillon, Namisha Leppert, Phyllis Segars, James H. TI Mechanical homeostasis is altered in uterine leiomyoma SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the American-Gynecological-and-Obstetrical-Society CY SEP 26-29, 2007 CL Chicago, IL SP Amer Gynecol & Obstet Soc DE AKAP13; brx; fibroid; mechanotransduction; RhoA; solid-state signaling ID NUCLEOTIDE EXCHANGE FACTOR; SMOOTH-MUSCLE-CELLS; NORMAL MYOMETRIUM; BIOLOGICAL TISSUES; GENE ARRAYS; RHO-GTPASES; EXPRESSION; RECEPTOR; STRETCH; ACTIVATION AB OBJECTIVE: Uterine leiomyoma produce an extracellular matrix (ECM) that is abnormal in its volume, content, and structure. Alterations in ECM can modify mechanical stress on cells and lead to activation of Rho-dependent signaling and cell growth. Here we sought to determine whether the altered ECM that is produced by leiomyoma was accompanied by an altered state of mechanical homeostasis. STUDY DESIGN: We measured the mechanical response of paired leiomyoma and myometrial samples and performed immunogold, confocal microscopy, and immunohistochemical analyses. RESULTS: Leiomyoma were significantly stiffer than matched myometrium. The increased stiffness was accompanied by alteration of the ECM, cell shape, and cytoskeleton in leiomyoma, compared with myometrial samples from the same uterus. Levels of AKAP13, a protein that is known to activate Rho, were increased in leiomyoma compared to myometrium. AKAP13 was associated with cytoskeletal filaments of immortalized leiomyoma cells. CONCLUSION: Leiomyoma cells are exposed to increased mechanical loading and show structural and biochemical features that are consistent with the activation of solid-state signaling. C1 [Rogers, Rebecca; Norian, John; Christman, Gregory; Catherino, William H.; Dhillon, Namisha; Leppert, Phyllis; Segars, James H.] NICHD, CRC, NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Abu-Asab, Mones] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Chen, Faye; Tuan, Rocky S.] NIAMS, Cartialage Biol & Orthopaed Branch, NIH, Bethesda, MD USA. [Malik, Minnie; Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Christman, Gregory] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Korecki, Casey; Iatridis, James] Univ Vermont, Sch Engn, Burlington, VT USA. RP Segars, JH (reprint author), NICHD, CRC, NIH, Reprod Biol & Med Branch, Bldg 10,1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM segarsj@mail.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232; Malik, Minnie/0000-0003-1129-6575 FU Howard Hughes Medical Institute; Intramural NIH HHS [Z01 HD008737-07]; NICHD NIH HHS [Z01 HD008737] NR 44 TC 16 Z9 16 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2008 VL 198 IS 4 AR 474.e1 DI 10.1016/j.ajog.2007.11.057 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 288IR UT WOS:000254980200063 PM 18395046 ER PT J AU Shafiee, R Korn, EL Pearson, H Boyd, RL Baumrind, S AF Shafiee, Roxanne Korn, Edward L. Pearson, Helmer Boyd, Robert L. Baumrind, Sheldon TI Evaluation of facial attractiveness from end-of-treatment facial photographs SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS LA English DT Article ID SMILES; FACES AB Introduction: Orthodontists typically make judgments of facial attractiveness by examining groupings of profile, full-face, and smiling photographs considered together as a "triplet." The primary objective of this study was to determine the relative contributions of the 3 photographs-each considered separately - to the overall judgment a clinician forms by examining the combination of the 3. Methods: End-of-treatment triplet orthodontic photographs of 45 randomly selected orthodontic patients were duplicated. Copies of the profile, full-face, and smiling images were generated, and the images were separated and then pooled by image type for all subjects. Ten judges ranked the 45 photographs of each image type for facial attractiveness in groups of 9 to 12, from "most attractive" to "least attractive." Each judge also ranked the triplet groupings for the same 45 subjects. The mean attractiveness rankings for each type of photograph were then correlated with the mean rankings of each other and the triplets. Results: The rankings of the 3 image types correlated highly with each other and the rankings of the triplets (P <. 0001). The rankings of the smiling photographs were most predictive of the rankings of the triplets (r = 0.93); those of the profile photographs were the least predictive (r = 0.76). The difference between these correlations was highly statistically significant (P =.0003). It was also possible to test the extent to which the judges' rankings were influenced by sex, original Angle classification, and extraction status of each patient. No statistically significant preferences were found for sex or Angle classification, and only 1 marginally significant preference was found for extraction pattern. Conclusions: Clinician judges demonstrated a high level of agreement in ranking the facial attractiveness of profile, full-face, and smiling photographs of a group of orthodontically treated patients whose actual differences in physical dimensions were relatively small. The judges' rankings of the smiling photographs were significantly better predictors of their rankings of the triplet of each patient than were their rankings of the profile photographs. C1 [Shafiee, Roxanne] Univ Pacific, Sch Dent, Dept Restorat Dent, San Francisco, CA 94115 USA. [Korn, Edward L.] NCI, NIH, Biometr Res Branch, Rockville, MD USA. [Pearson, Helmer] Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Orthodont, Newark, NJ 07103 USA. [Boyd, Robert L.; Baumrind, Sheldon] Univ Pacific, Sch Dent, Dept Orthodont, San Francisco, CA 94115 USA. [Baumrind, Sheldon] Univ Pacific, Sch Dent, CRIL, San Francisco, CA 94115 USA. RP Baumrind, S (reprint author), Univ Pacific, Arthur A Dugoni Sch Dent, CRIL, Room 617,2115 Webster St, San Francisco, CA 94115 USA. EM sbaumrind@pacific.edu NR 24 TC 11 Z9 11 U1 1 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0889-5406 J9 AM J ORTHOD DENTOFAC JI Am. J. Orthod. Dentofac. Orthop. PD APR PY 2008 VL 133 IS 4 BP 500 EP 508 DI 10.1016/j.ajodo.2006.04.048 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 287NL UT WOS:000254923700016 PM 18405813 ER PT J AU Satoh, K Hamada, S Kimura, K Kanno, A Hirota, M Umino, J Fujibuchi, W Masamune, A Tanaka, N Miura, K Egawa, S Motoi, F Unno, M Vonderhaar, BK Shimosegawa, T AF Satoh, Kennichi Hamada, Shin Kimura, Kenji Kanno, Atsushi Hirota, Morihisa Umino, Jun Fujibuchi, Wataru Masamune, Atsushi Tanaka, Naoki Miura, Koh Egawa, Shinichi Motoi, Fuyuhiko Unno, Michiaki Vonderhaar, Barbara K. Shimosegawa, Tooru TI Up-regulation of MSX2 enhances the malignant phenotype and is associated with Twist 1 expression in human pancreatic cancer cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MAMMARY-GLAND DEVELOPMENT; EPITHELIAL-MESENCHYMAL TRANSITIONS; MUCIN-HYPERSECRETING NEOPLASMS; HUMAN BREAST-CANCER; HOMEOBOX GENES; BETA-CATENIN; CYCLIN D1; POOR-PROGNOSIS; MURINE SKULL; IN-VITRO AB MSX2 is thought to be a regulator of organ development and a downstream target of the ras signaling pathway; however, little is known about the role of MSX2 in the development of pancreatic cancers, most of which harbor a K-ras gene mutation. Therefore, we examined whether the presence of MSX2 correlates with the malignant behavior of pancreatic cancer cells. BxPC3 pancreatic cancer cells that stably overexpress MSX2 showed a flattened and scattered morphology accompanied by a change in localization of E-cadherin and beta-catenin from membrane to cytoplasm. Cell proliferation rate, cell migration, and anchorage-independent cell growth were enhanced in MSX2-expressing cells. Injection of MSX2-expressing cells into the pancreas of nude mice resulted in a significant increase in liver metastases and peritoneal disseminations compared with injection of control cells. Microarray analysis revealed a significant induction of Twist 1 expression in cells that express MSX2. When MSX2 was inactivated in pancreatic cancer cells following transfection with an MSX2-specific small interfering RNA, Twist 1 was down-regulated. Immunohistochemistry of human pancreatic carcinoma tissue revealed that MSX2 was frequently expressed in cancer cells, and that increased expression of MSX2 significantly correlated with higher tumor grade, vascular invasion, and Twist I expression. These data indicate that MSX2 plays a crucial role in pancreatic cancer development by inducing changes consistent with epithelial to mesenchymal transition through enhanced expression of Twist 1. C1 [Satoh, Kennichi; Hamada, Shin; Kimura, Kenji; Kanno, Atsushi; Hirota, Morihisa; Umino, Jun; Masamune, Atsushi; Shimosegawa, Tooru] Tohoku Univ, Grad Sch Med, Div Gastroenterol, Aoba Ku, Sendai, Miyagi 9808574, Japan. [Tanaka, Naoki; Miura, Koh; Egawa, Shinichi; Motoi, Fuyuhiko; Unno, Michiaki] Tohoku Univ, Grad Sch Med, Dept Surg Gastroenterol, Sendai, Miyagi 9808574, Japan. [Fujibuchi, Wataru] Adv Ind Sci & Technol, Koto Ku, Tokyo, Japan. [Vonderhaar, Barbara K.] NIH, Mammary Biol & Tumorigenesis Lab, Natl Canc Inst, Bethesda, MD 20892 USA. RP Satoh, K (reprint author), Tohoku Univ, Grad Sch Med, Div Gastroenterol, Aoba Ku, 1-1 Siryo Machi, Sendai, Miyagi 9808574, Japan. EM ksatoh@mail.tains.tohoku.ac.jp RI Unno, Michiaki/A-8633-2010; OI Unno, Michiaki/0000-0002-2145-6416; Miura, Koh/0000-0001-7303-9430 NR 52 TC 43 Z9 48 U1 1 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2008 VL 172 IS 4 BP 926 EP 939 DI 10.2353/ajpath.2008.070346 PG 14 WC Pathology SC Pathology GA 283YO UT WOS:000254672600009 PM 18349132 ER PT J AU Chen, GJ Han, GC Wang, JA Wang, RX Xu, RN Shen, BF Qian, JH Li, Y AF Chen, Guojiang Han, Gencheng Wang, Jianan Wang, Renxi Xu, Ruonan Shen, Beifen Qian, Jiahua Li, Yan TI Induction of active tolerance and involvement of CD1d-restricted natural killer T cells in anti-CD3 F(ab ')(2) treatment-reversed new-onset diabetes in nonobese diabetic mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ALPHA-GALACTOSYLCERAMIDE; NKT CELLS; NOD MOUSE; IMMUNE DYSREGULATION; MONOCLONAL-ANTIBODY; LYMPH-NODES; TGF-BETA; MELLITUS; THERAPY; ACTIVATION AB The application of anti-CD3 F(ab ')(2) monoclonal antibodies has recently been expanded to treat established autoimmune diseases, including type 1 diabetes. However, the mechanism underlying their effect remains largely unclear. We report that short-phase administration of anti-CD3 F(ab ')(2) antibodies efficiently allowed 80% of new-onset, nonobese diabetic (NOD) mice to significantly regain both normoglycemia and pancreatic beta cell-specific autoantigen (ie, glutamic acid decarboxylase and insulin) tolerance, with both effects lasting more than 40 weeks. The responsible mechanism appears to involve the induction and maintenance of a population of immunoregulatory CD1d-restricted natural killer T (NKT) cells, which were marked by an enhanced Th2 response and secretion of elevated levels of interleukin-10. In vivo neutralization of interleukin-4 and/or interleukin-10 bioactivity abrogated this anti-CD3-mediated effect. Importantly, when the cotransfer of NKT cells from the fivers of anti-CD3-treated mice and splenocytes; from untreated, acutely diabetic NOD mice was performed in NOD-severe combined immunodeficient mice, the NKT cells were sufficient to either delay or prevent the onset of diabetes compared with controls where only splenocytes; were introduced. These data suggest that CD1d-restricted NKT cells may play a critical role in anti-CD3 antibody-induced diabetes remission and the restoration of immune tolerance. C1 [Chen, Guojiang; Han, Gencheng; Wang, Jianan; Wang, Renxi; Xu, Ruonan; Shen, Beifen; Li, Yan] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China. [Qian, Jiahua] NIH, Vaccine Branch, Natl Canc Inst, Bethesda, MD 20892 USA. RP Li, Y (reprint author), Chinese Acad Med Sci, Inst Basic Med Sci, Dept Mol Immunol, Taiping Rd 27, Beijing 100850, Peoples R China. EM liyan62033@yahoo.com.cn NR 47 TC 7 Z9 7 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2008 VL 172 IS 4 BP 972 EP 979 DI 10.2353/ajpath.2008.070159 PG 8 WC Pathology SC Pathology GA 283YO UT WOS:000254672600013 PM 18349126 ER PT J AU Waldo, SW Li, YF Buono, C Zhao, B Billings, EM Chang, J Kruth, HS AF Waldo, Stephen W. Li, Yifu Buono, Chiara Zhao, Bin Billings, Eric M. Chang, Janet Kruth, Howard S. TI Heterogeneity of human macrophages in culture and in atherosclerotic plaques SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; MONOCYTE-DERIVED MACROPHAGES; FOAM-CELL-FORMATION; LIVER-X-RECEPTORS; CORONARY-ARTERY-DISEASE; LOW-DENSITY-LIPOPROTEIN; APOE-DEFICIENT MICE; GENE-EXPRESSION; MONOCLONAL-ANTIBODY; CHOLESTEROL EFFLUX AB Research suggests that monocytes differentiate into unique lineage-determined macrophage subpopulations in response to the local cytokine environment. The present study evaluated the atherogenic potential of two divergent lineage-determined human monocyte-derived macrophage subpopulations. Monocytes were differentiated for 7 days in the presence of alternative macrophage development cytokines: granulocyte-macrophage colony-stimulating factor to produce granutocyte-macrophage-CSF macrophages (GM-Mac), or macrophage colony-stimulating factor (M-CSF) to produce M-Mac. Gene chip analyses of three monocyte donors demonstrated differential expression of inflammatory and cholesterol homeostasis genes in the macrophage subpopulations. Quantitative PCR confirmed a fivefold elevation in the expression of genes that promote reverse cholesterol transport (PPAR-gamma, LXR-alpha, and ABCG1) and macrophage emigration from lesions (CCR7) in GM-Mac compared to that in M-Mac. Immunocytochemistry confirmed enhanced expression of the proinflammatory marker CD14 in M-Mac relative to GM-Mac. M-Mac spontaneously accumulated cholesterol when incubated with unmodified low-density lipoprotein whereas GM-Mac only accumulated similar levels of cholesterol after protein kinase C activation. Immunostained human coronary arteries showed that macrophages with similar antigen expression to that of M-Mac (CD68(+)/CD14(+)) were predominant within atherosclerotic lesions whereas macrophages with antigen expression similar to GM-Mac (CD68(+)/CD14(+)) were predominant in areas devoid of disease. The identification of macrophage subpopulations with different gene expression patterns and, thus, different potentials for promoting atherosclerosis has important experimental and clinical implications and could prove to be a valuable finding in developing therapeutic interventions in diseases dependent on macrophage function. C1 [Waldo, Stephen W.; Li, Yifu; Buono, Chiara; Zhao, Bin; Chang, Janet; Kruth, Howard S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. [Billings, Eric M.] NHLBI, Bioinformat Core Facil, NIH, Bethesda, MD 20892 USA. [Waldo, Stephen W.] NIH, Med Res Scholar Program, Howard Hughes Med Inst, Chevy Chase, MD USA. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10,Room 5N-113,10 Ctr Dr,MSC 1422, Bethesda, MD 20892 USA. EM kruthh@nhlbi.nih.gov FU Howard Hughes Medical Institute; Intramural NIH HHS NR 76 TC 129 Z9 142 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2008 VL 172 IS 4 BP 1112 EP 1126 DI 10.2353/ajpath.2008.070513 PG 15 WC Pathology SC Pathology GA 283YO UT WOS:000254672600026 PM 18321997 ER PT J AU Mastrobattista, JM Klebanoff, MA Carey, JC Hauth, JC MacPherson, CA Ernest, J Cotroneo, M Leveno, KJ Wapner, R Varner, M Iams, JD Moawad, A Sibai, BM Miodovnik, M Dombrowski, M O'Sullivan, MJ VanDorsten, JP Langer, O AF Mastrobattista, Joan M. Klebanoff, Mark A. Carey, J. Christopher Hauth, John C. MacPherson, Cora A. Ernest, J. Cotroneo, Margaret Leveno, Kenneth J. Wapner, Ronald Varner, Michael Iams, Jay D. Moawad, Atef Sibai, Baha M. Miodovnik, Menachem Dombrowski, Mitchell O'Sullivan, Mary J. VanDorsten, J. Peter Langer, Oded CA Natl Inst Child Hlth Human Dev TI The effect of body mass index on therapeutic response to bacterial vaginosis in pregnancy SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE body mass index; bacterial vaginosis; pregnancy; treatment ID PRETERM DELIVERY; WOMEN; BIRTH; PHARMACOKINETICS; METRONIDAZOLE; AGENTS; RISK AB Our objective was to determine the effect of body mass index (BMI) on response to bacterial vaginosis (BV) treatment. A secondary analysis was conducted of two multi-center trials of therapy for BV and Tricbomonas vaginalis. Gravida were screened for BV between 8 and 22 weeks and randomized between 16 and 23 weeks to metronidazole or placebo. Of 1497 gravida with asymptomatic BV and preconceptional BMI, 738 were randomized to metronidazole; BMI was divided into categories: < 25, 25 to 29.9, and >= 30. Rates of BV persistence at follow-up were compared using the Mantel-Haenszel chi square. Multiple logistic regression was used to evaluate the effect of BMI on BV persistence at follow-up, adjusting for potential confounders. No association was identified between BMI and BV rate at follow-up (p = 0.21). BMI was associated with maternal age, smoking, marital status, and black race. Compared with women with BMI of < 25, adjusted odds ratio (OR) of BV at follow-up were BMI 25 to 29.9: OR, 0.66, 95% CI 0.43 to 1.02; BMI >= 30: OR, 0.83, 95% CI 0.54 to 1.26. We concluded that the persistence of BV after treatment was not related to BMI. C1 [Mastrobattista, Joan M.] Univ Texas Houston, Hlth Sci Ctr, Dept Obstet Gynecol & Reprod Sci, Houston, TX 77030 USA. [Klebanoff, Mark A.] NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Carey, J. Christopher] Univ Colorado, Sch Med, Denver, CO USA. [Hauth, John C.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [MacPherson, Cora A.] George Washington Univ, Dept Epidemiol & Biostat, Rockville, MD USA. [Ernest, J.] Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. [Cotroneo, Margaret] Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. [Wapner, Ronald] Columbia Med Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, New York, NY USA. [Varner, Michael] Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Iams, Jay D.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Moawad, Atef] Univ Chicago, Dept Obstet & Gynecol, Med Ctr, Chicago, IL 60637 USA. [Sibai, Baha M.] Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. [Miodovnik, Menachem] Washington Hosp Ctr, Dept Obstet & Gynecol, Washington, DC 20010 USA. [Dombrowski, Mitchell] St Johns Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [O'Sullivan, Mary J.] Univ Miami, Div Res, Dept Obstet & Gynecol, Miami, FL 33152 USA. [VanDorsten, J. Peter] Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. [Langer, Oded] St Lukes Roosevelt Hosp, Dept Obstet & Gynecol, New York, NY 10025 USA. RP Mastrobattista, JM (reprint author), Univ Texas Houston, Hlth Sci Ctr, Dept Obstet Gynecol & Reprod Sci, 6431 Fannin St,Room 3-274, Houston, TX 77030 USA. RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU NIAID NIH HHS [AI38514, U19 AI038514]; NICHD NIH HHS [U10 HD034136, HD21410, HD21414, HD27860, HD27861, HD27869, HD27889, HD27915, HD27917, HD34116, HD34136, HD34208, HD34210, HD36801, U01 HD019897, U01 HD019897-130001, U01 HD036801, U10 HD021410, U10 HD021410-22, U10 HD021414-15, U10 HD027860, U10 HD027860-15, U10 HD027861-10, U10 HD027869, U10 HD027869-10, U10 HD027883, U10 HD027883-06, U10 HD027905, U10 HD027905-10, U10 HD027915, U10 HD027915-18, U10 HD027917, U10 HD027917-18, U10 HD034116, U10 HD034116-13, U10 HD034122, U10 HD034122-05, U10 HD034136-10, U10 HD034208, U10 HD034208-12, U10 HD034210-05, U10 HD036801, U10 HD036801-11, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208] NR 15 TC 3 Z9 3 U1 0 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD APR PY 2008 VL 25 IS 4 BP 233 EP 237 DI 10.1055/s-2008-1066875 PG 5 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 289DW UT WOS:000255036200007 PM 18548397 ER PT J AU Bergouignan, A Schoeller, DA Votruba, S Simon, C Blanc, S AF Bergouignan, Audrey Schoeller, Dale A. Votruba, Susanne Simon, Chantal Blanc, Stephane TI The acetate recovery factor to correct tracer-derived dietary fat oxidation in humans SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE exogenous fatty acid oxidation; stable isotopes; mass spectrometry ID ACID OXIDATION; EXERCISE; (CO2)-C-13; VALIDATION; CO2; BICARBONATE; REST; C-13 AB When using C-13 tracer to measure plasma fat oxidation, an acetate recovery factor should be determined in every subject to correct for label sequestration. Less is known regarding the acetate recovery factor for dietary fatty acid oxidation. We compiled data from six studies to investigate the determinants of the dietary acetate recovery factor (dARF) at rest and after physical activity interventions and compared the effects of different methods of dARF calculation on both the fat oxidation and its variability. In healthy lean subjects, dARF was 50.6 +/- 5.4% dose (n = 56) with an interindividual coefficient of variation of 10.6% at rest and 9.2% after physical activity modifications. The physical activity interventions did not impact dARF, and the intraindividual coefficient of variation was 4.6%. No major anthropological or physiological determinants were detected except for resting metabolic rate, which explains 7.4% of the dARF variability. Applying an individual or an average group dARF did not affect the mean and the variability of the derived dietary lipid oxidation at rest or after physical activity interventions. Using a mean dARF for a group leads to over- or underestimation of fat oxidation of less than 10% in individual subjects. Moreover, the use of a group or individual correction did not affect the significant relationship found between fasting respiratory exchange ratio and dietary fat oxidation. These data indicate that an average dARF can be applied for longitudinal and cross-sectional studies investigating dietary lipid metabolism. C1 [Bergouignan, Audrey; Blanc, Stephane] Univ Strasbourg 1, CNRS, UMR 7178, Dept Ecol Physiol Ethol,Inst Pluridisciplinaire H, F-67087 Strasbourg, France. [Schoeller, Dale A.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Votruba, Susanne] NIDDK, Obes & Diabet Res Sect, NIH, Phoenix, AZ USA. [Simon, Chantal] Univ Strasbourg 1, Hop Hautepierre, Dept Nutr, F-67087 Strasbourg, France. RP Blanc, S (reprint author), Univ Strasbourg 1, CNRS, UMR 7178, Dept Ecol Physiol Ethol,Inst Pluridisciplinaire H, 23 Rue Becquerel, F-67087 Strasbourg, France. EM stephane.blanc@c-strasbourg.fr RI Simon, Chantal/B-2895-2011; Bergouignan, Audrey/A-2750-2016 OI Simon, Chantal/0000-0002-7820-3233; Bergouignan, Audrey/0000-0002-1266-5144 NR 22 TC 8 Z9 8 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 2008 VL 294 IS 4 BP E645 EP E653 DI 10.1152/ajpendo.00720.2007 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 282NU UT WOS:000254575300001 PM 18212023 ER PT J AU Pacher, P Gao, B AF Pacher, Pal Gao, Bin TI Endocannabinoids and Liver Disease. III. Endocannabinoid effects on immune cells: implications for inflammatory liver diseases SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE ischemia-reperfusion; endocannabinoids; cannabinoid 2 receptor; inflammation; endothelium ID HEPATIC ISCHEMIA/REPERFUSION INJURY; CANNABINOID RECEPTORS; ISCHEMIA-REPERFUSION; CIRRHOTIC RATS; CB1; FIBROSIS; SYSTEM; DYSFUNCTION; APOPTOSIS; MIGRATION AB Recent studies have implicated dysregulation of the endocannabinoid system in various liver diseases and their complications ( e. g., hepatitis, fibrosis, cirrhosis, cirrhotic cardiomyopathy, and ischemia-reperfusion), and demonstrated that its modulation by either cannabinoid 2 (CB2) receptor agonists or CB1 antagonists may be of significant therapeutic benefits. This review is aimed to focus on the triggers and sources of endocannabinoids during liver inflammation and on the novel role of CB2 receptors in the interplay between the activated endothelium and various inflammatory cells ( leukocytes, lymphocytes, etc.), which play pivotal role in the early development and progression of inflammatory and other liver diseases. C1 [Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Sect Oxidat Stress Tissue Injury, Bethesda, MD 20892 USA. [Gao, Bin] NIAAA, Lab Physiol Studies, NIH, Sect Liver Biol, Bethesda, MD 20892 USA. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, Sect Oxidat Stress Tissue Injury, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z99 AA999999, Z01 AA000375-02] NR 27 TC 30 Z9 30 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 2008 VL 294 IS 4 BP G850 EP G854 DI 10.1152/ajpgi.00523.2007 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 285PP UT WOS:000254789000003 PM 18239059 ER PT J AU Shen, KZ Zheng, SS Park, OY Wang, H Sun, ZL Gao, B AF Shen, Kezhen Zheng, Shu-Sen Park, Ogyi Wang, Hua Sun, Zhaoli Gao, Bin TI Activation of innate immunity (NK/IFN-gamma) in rat allogeneic liver transplantation: contribution to liver injury and suppression of hepatocyte proliferation SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE liver regeneration; NK cells; STAT1; IRF-1; p21 ID NATURAL-KILLER-CELLS; IFN-GAMMA; NK CELLS; NEGATIVE REGULATION; MEDIATED HEPATITIS; OPPOSING ROLES; REGENERATION; APOPTOSIS; MICE; TOLERANCE AB Liver transplantation is presently the only curative treatment for patients with end-stage liver disease. However, the mechanisms underlying liver injury and hepatocyte proliferation posttransplantation remain obscure. In this investigation, liver injury and hepatocyte proliferation in syngeneic and allogeneic animal models were compared. Male Lewis and Dark Agouti (DA) rats were subjected to orthotopic liver transplantation (OLT). Rat OLT was performed in syngeneic (Lewis-Lewis) and allogeneic (Lewis-DA or DA-Lewis) animal models. Allogeneic liver grafts exhibited greater injury and cellular apoptosis than syngeneic grafts but less hepatocyte proliferation after OLT. Expression of IFN-gamma mRNA and activation of the downstream signal transducer and activator of transcription 1 (STAT1) and genes (interferon regulatory factor-1 and cyclin-dependent kinase inhibitor p21(CDKN1A)) were also greater in the allogeneic grafts compared with the syngeneic grafts. In contrast, STAT3 activation was lower in the allogeneic grafts. Furthermore, in the allogeneic grafts, depletion of natural killer (NK) cells decreased IFN-gamma/STAT1 activation but enhanced hepatocyte proliferation. These findings suggest that, compared with syngeneic transplantation, innate immunity (NK/IFN-gamma) is activated after allogeneic transplantation, which likely contributes to liver injury and inhibits hepatocyte proliferation. C1 [Shen, Kezhen; Zheng, Shu-Sen] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Hepatobiliary Surg, Hangzhou 310027, Peoples R China. [Shen, Kezhen; Park, Ogyi; Wang, Hua; Gao, Bin] NIAAA, Sexct Liver Biol, NIH, Bethesda, MD 20892 USA. [Sun, Zhaoli] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. RP Gao, B (reprint author), NIAAA, Sexct Liver Biol, NIH, 5625 Fishers Ln,Rm 2S-33, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov FU Intramural NIH HHS [Z01 AA000368-06] NR 47 TC 20 Z9 21 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 2008 VL 294 IS 4 BP G1070 EP G1077 DI 10.1152/ajpgi.00554.2007 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 285PP UT WOS:000254789000028 PM 18292182 ER PT J AU Swoap, SJ Li, C Wess, J Parsons, AD Williams, TD Overton, JM AF Swoap, S. J. Li, C. Wess, J. Parsons, A. D. Williams, T. D. Overton, J. M. TI Vagal tone dominates autonomic control of mouse heart rate at thermoneutrality SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE telemetry; intrinsic heart rate; cold stress; caloric restriction; sympathetic nervous system ID SYMPATHETIC NERVOUS-SYSTEM; ION-CHANNEL EXPRESSION; BLOOD-PRESSURE; RATE-VARIABILITY; CALORIC RESTRICTION; C57BL/6J MICE; CARDIOVASCULAR PARAMETERS; CONSCIOUS MICE; METABOLIC-RATE; RESPONSES AB It is generally accepted that cardiac sympathetic tone dominates the control of heart rate (HR) in mice. However, we have recently challenged this notion given that HR in the mouse is responsive to ambient temperature (T-a) and that the housing Ta is typically 21-23 degrees C, well below the thermoneutral zone (similar to 30 degrees C) of this species. To specifically test the hypothesis that cardiac sympathetic tone is the primary mediator of HR control in the mouse, we first examined the metabolic and cardiovascular responses to rapid changes in Ta to demonstrate the sensitivity of the mouse cardiovascular system to Ta. We then determined HR in 1) mice deficient in cardiac sympathetic tone ("beta-less" mice), 2) mice deficient in cardiac vagal tone [muscarinic M-2 receptor (M2R-/-) mice], and 3) littermate controls. At a Ta of 30 C, the HR of beta-less mice was identical to that of wild-type mice (351 +/- 11 and 363 +/- 10 beats/min, respectively). However, the HR of M2R(-/-) mice was significantly greater (416 +/- 7 beats/min), demonstrating that vagal tone predominates over HR control at this Ta. When these mice were calorically restricted to 70% of normal intake, HR fell equally in wild-type, beta-less, and M2R(-/-) mice (Delta HR = 73 +/- 9, 76 +/- 3, and 73 +/- 7 beats/min, respectively), suggesting that the fall in intrinsic HR governs bradycardia of calorically restricted mice. Only when the Ta was relatively cool, at 23 degrees C, did beta-less mice exhibit a HR (442 +/- 14 beats/min) that was different from that of littermate controls (604 +/- 10 beats/min) and M2R(-/-) mice (602 +/- 5 beats/min). These experiments conclusively demonstrate that in the absence of cold stress, regulation of vagal tone and modulation of intrinsic rate are important determinants of HR control in the mouse. C1 [Parsons, A. D.; Overton, J. M.] Florida State Univ, Coll Med, Dept Biomed Sci, Tallahassee, FL 32306 USA. [Swoap, S. J.; Li, C.] Williams Coll, Dept Biol, Williamstown, MA 01267 USA. [Wess, J.] NIDDK, Bioorgan Chem Lab, Bethesda, MD USA. [Williams, T. D.] Univ Cambridge Emmanuel Coll, Dept Biol, Boston, MA USA. RP Overton, JM (reprint author), Florida State Univ, Coll Med, Dept Biomed Sci, 3350-E, Tallahassee, FL 32306 USA. EM mike.overton@fsu.edu FU NHLBI NIH HHS [R01-HL-56732, R15-HL-081101-01] NR 59 TC 44 Z9 45 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2008 VL 294 IS 4 BP H1581 EP H1588 DI 10.1152/ajpheart.01000.2007 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 282NR UT WOS:000254575000011 PM 18245567 ER PT J AU Anderson, DE Fedorova, OV Morrell, CH Longo, DL Kashkin, VA Metzler, JD Bagrov, AY Lakatta, EG AF Anderson, David E. Fedorova, Olga V. Morrell, Christopher H. Longo, Dan L. Kashkin, Vladimir A. Metzler, Jessica D. Bagrov, Alexei Y. Lakatta, Edward G. TI Endogenous sodium pump inhibitors and age-associated increases in salt sensitivity of blood pressure in normotensives SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE marinobufagenin; ouabain; hypertension ID DIETARY-SODIUM; DEPENDENT HYPERTENSION; ATPASE INHIBITION; MARINOBUFAGENIN; OUABAIN; RATS; LIGAND; POTASSIUM AB Factors that mediate increases in salt sensitivity of blood pressure with age remain to be clarified. The present study investigated 1) the effects of high-NaCl intake on two Na pump inhibitors, endogenous ouabain (EO) and marinobufagenin (MBG), in middle-aged and older normotensive Caucasian women; and 2) whether individual differences in EO and MBG are linked to variations in sodium excretion or salt sensitivity. A change from 6 days of a lower (0.7 mmol(.)kg(-1.)day(-1))-to 6 days of a higher (4 mmol(.)kg(-1.)day(-1))-NaCl diet elicited a sustained increase in MBG excretion that directly correlated with an increase in the fractional Na excretion and was inversely related to age and to an age-dependent increase in salt sensitivity. In contrast, EO excretion increased only transiently in response to NaCl loading and did not vary with age or correlate with fractional Na excretion or salt sensitivity. A positive correlation of both plasma and urine levels of EO and MBG during salt loading may indicate a casual link between two Na pump inhibitors in response to NaCl loading, as observed in animal models. A linear mixed-effects model demonstrated that age, dietary NaCl, renal MBG excretion, and body mass index were each independently associated with systolic blood pressure. Thus, a sustained increase in MBG in response to acutely elevated dietary NaCl is inversely linked to salt sensitivity in normotensive middle-aged and older women, and a relative failure of MBG elaboration by these older persons may be involved in the increased salt sensitivity with advancing age. C1 [Anderson, David E.; Fedorova, Olga V.; Morrell, Christopher H.; Kashkin, Vladimir A.; Bagrov, Alexei Y.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Anderson, David E.; Longo, Dan L.; Metzler, Jessica D.] NIA, Clin Res Branch, Intramural Res Program, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Morrell, Christopher H.] Loyola Coll, Dept Math Sci, Baltimore, MD 21210 USA. RP Lakatta, EG (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lakattae@mail.nih.gov OI Kashkin, Vladimir/0000-0002-7202-0233 FU Intramural NIH HHS [Z01 AG000609-15] NR 35 TC 30 Z9 30 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD APR PY 2008 VL 294 IS 4 BP R1248 EP R1254 DI 10.1152/ajpregu.00782.2007 PG 7 WC Physiology SC Physiology GA 282NN UT WOS:000254574600018 PM 18287222 ER PT J AU Kim, GH Choi, NW Jung, JY Song, JH Lee, CH Kang, CM Knepper, MA AF Kim, Gheun-Ho Choi, Nak Won Jung, Ju-Young Song, Ji-Hyun Lee, Chang Hwa Kang, Chong Myung Knepper, Mark A. TI Treating lithium-induced nephrogenic diabetes insipidus with a COX-2 inhibitor improves polyuria via upregulation of AQP2 and NKCC2 SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cyclooxygenase-2; lithium; aquaporin-2; Na-K-2Cl cotransporter; DFU ID THICK ASCENDING LIMB; NA-K-2CL COTRANSPORTER ABUNDANCE; CORTICAL COLLECTING DUCT; PROSTAGLANDIN SYNTHESIS; SODIUM-TRANSPORT; DOWN-REGULATION; WATER CHANNEL; TOAD BLADDER; RENAL WATER; HENLES LOOP AB Prostaglandin E(2) may antagonize vasopressin-stimulated salt absorption in the thick ascending limb and water absorption in the collecting duct. Blockade of prostaglandin E2 synthesis by nonsteroidal anti-inflammatory drugs (NSAIDs) enhances urinary concentration, and these agents have antidiuretic effects in patients with nephrogenic diabetes insipidus (NDI) of different etiologies. Because renal prostaglandins are derived largely from cyclooxygenase-2 (COX-2), we hypothesized that treatment of NDI with a COX-2 inhibitor may relieve polyuria through increased expression of Na-K-2Cl cotransporter type 2 (NKCC2) in the thick ascending limb and aquaporin-2 (AQP2) in the collecting duct. To test this hypothesis, semiquantitative immunoblotting and immunohistochemistry were carried out from the kidneys of lithium-induced NDI rats with and without COX-2 inhibition. After male Sprague-Dawley rats were fed an LiCl-containing rat diet for 3 wk, the rats were randomly divided into control and experimental groups. The COX-2 inhibitor DFU (40 mg center dot kg(-1) center dot day(-1)) was orally administered to the experimental rats for an additional week. Treatment with the COX-2 inhibitor significantly relieved polyuria and raised urine osmolality. Semiquantitative immunoblotting using whole-kidney homogenates revealed that COX-2 inhibition caused significant increases in the abundance of AQP2 and NKCC2. Immunohistochemistry for AQP2 and NKCC2 confirmed the effects of COX-2 inhibition in lithium-induced NDI rats. The upregulation of AQP2 and NKCC2 in response to the COX-2 inhibitor may underlie the therapeutic mechanisms by which NSAIDs enhance antidiuresis in patients with NDI. C1 [Kim, Gheun-Ho; Lee, Chang Hwa; Kang, Chong Myung] Hanyang Univ, Dept Internal Med, Coll Med, Seoul 133792, South Korea. [Kim, Gheun-Ho] Hanyang Univ, Inst Biomed Sci, Seoul 133791, South Korea. [Choi, Nak Won] Konyang Univ, Dept Internal Med, Coll Med, Nonsan, South Korea. [Jung, Ju-Young; Song, Ji-Hyun] Chungnam Natl Univ, Dept Anat, Coll Vet Med, Taejon, South Korea. [Knepper, Mark A.] NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Kim, GH (reprint author), Hanyang Univ, Dept Internal Med, Coll Med, 17 Haengdang Dong, Seoul 133792, South Korea. EM kimgh@hanyang.ac.kr OI Kim, Gheun-Ho/0000-0002-8445-9892 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 48 TC 22 Z9 22 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2008 VL 294 IS 4 BP F702 EP F709 DI 10.1152/ajprenal.00366.2007 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 283FX UT WOS:000254623200003 PM 18216147 ER PT J AU Oppermann, M Friedman, DJ Faulhaber-Walter, R Mizel, D Castrop, H Enjyoji, K Robson, SC Schnermann, J AF Oppermann, Mona Friedman, David J. Faulhaber-Walter, Robert Mizel, Diane Castrop, Hayo Enjyoji, Keiichi Robson, Simon C. Schnermann, Jurgen TI Tubuloglomerular feedback and renin secretion in NTPDase1/CD39-deficient mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE adenosine 5'-triphosphate; CD73; stop flow pressure; phenylephrine; adenosine ID GLOMERULAR-FILTRATION-RATE; TARGETED DISRUPTION; PLASMA-RENIN; ADENOSINE; ATP; INHIBITION; KIDNEY; MEDIATION; RATS AB Tubuloglomerular feedback and renin secretion in NTPDase1/CD39- deficient mice. Am J Physiol Renal Physiol 294: F965-F970, 2008. First published February 6, 2008; doi:10.1152/ajprenal.00603.2007. -Studies in mice with null mutations of adenosine 1 receptor or ecto-5'-nucleotidase genes suggest a critical role of adenosine and its precursor 5'-AMP in tubulovascular signaling. To assess whether the source of juxtaglomerular nucleotides can be traced back to ATP dephosphorylation, experiments were performed in mice with a deficiency in NTPDase1/CD39, an ecto-ATPase catalyzing the formation of AMP from ATP and ADP. Urine osmolarity and glomerular filtration rate (GFR) were indistinguishable between NTPDase1/CD39(-/-) and wild-type (WT) mice. Maximum tubuloglomerular feedback (TGF) responses, as determined by proximal tubular stop flow pressure measurements, were reduced in NTPDase1/CD39(-/-) mice compared with controls (4.2 +/- 0.9 vs. 10.5 +/- 1.2 mmHg, respectively; P = 0.0002). Residual TGF responses gradually diminished after repeated changes in tubular perfusion flow averaging 2.9 +/- 0.9 ( on response) and 3.5 +/- 1.1 (off response) mmHg after the second and 2.2 +/- 0.5 (on response) and 1.5 +/- 0.8 ( off response) mmHg after the third challenge, whereas no fading of TGF responsiveness was observed in WT mice. Macula densa-dependent and pressure-dependent inhibition of renin secretion, as assessed by acute salt loading and phenylephrine injection, respectively, were intact in NTPDase1/CD39-deficient mice. In summary, NTPDase1/CD39-deficient mice showed a markedly compromised TGF regulation of GFR. These data support the concept of an extracellular dephosphorylation cascade during tubular-vascular signal transmission in the juxtaglomerular apparatus that is initiated by a regulated release of ATP from macula densa cells and results in adenosine-mediated afferent arteriole constriction. C1 [Oppermann, Mona; Faulhaber-Walter, Robert; Mizel, Diane; Castrop, Hayo; Schnermann, Jurgen] NIDDKD, NIH, Bethesda, MD 20892 USA. [Friedman, David J.; Enjyoji, Keiichi; Robson, Simon C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Schnermann, J (reprint author), NIDDKD, NIH, 10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL063972-06, R01 HL063972-04, R01 HL063972-07, R01 HL063972-05, R01 HL063972-08] NR 32 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2008 VL 294 IS 4 BP F965 EP F970 DI 10.1152/ajprenal.00603.2007 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 283FX UT WOS:000254623200033 PM 18256308 ER PT J AU Pratt, CA AF Pratt, Charlotte A. TI Findings from the 2007 active living research conference - Implications for future research SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID PHYSICAL-ACTIVITY; OBESITY; HEALTH C1 NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Pratt, CA (reprint author), NHLBI, Div Prevent & Populat Sci, NIH, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. EM prattc@nhlbi.nih.gov NR 15 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2008 VL 34 IS 4 BP 366 EP 368 DI 10.1016/j.amepre.2008.01.001 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 279TR UT WOS:000254378100016 PM 18374254 ER PT J AU Bu, LP Fee, E AF Bu, Liping Fee, Elizabeth TI John B. Grant: International statesman of public health SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 [Bu, Liping] Alma Coll, Dept Hist, Alma, MI USA. [Fee, Elizabeth] Natl Lib Med, NIH, Bethesda, MD USA. RP Bu, LP (reprint author), Alma Coll, Dept Hist, 614 W Super St, Alma, MI USA. EM bulipi@alma.edu NR 1 TC 2 Z9 2 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2008 VL 98 IS 4 BP 628 EP 629 DI 10.2105/AJPH.2007.129304 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 282VO UT WOS:000254595500015 PM 18309119 ER PT J AU Fee, E Cueto, M Brown, TM AF Fee, Elizabeth Cueto, Marcos Brown, Theodore M. TI WHO at 60: Snapshots from its first six decades SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID WORLD-HEALTH-ORGANIZATION C1 [Fee, Elizabeth] Natl Lib Med, Hist Med Div, NIH, Bethesda, MD 20894 USA. [Cueto, Marcos] Univ Peruana Cayetano Heredia, Fac Salud Publ, Lima, Peru. [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY USA. [Brown, Theodore M.] Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Natl Lib Med, Hist Med Div, NIH, 8600 Rockville Pike,Bldg 38,Room 1E-21, Bethesda, MD 20894 USA. EM feee@mail.nih.gov NR 17 TC 7 Z9 7 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2008 VL 98 IS 4 BP 630 EP 633 DI 10.2105/AJPH.2007.132449 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 282VO UT WOS:000254595500016 PM 18309116 ER PT J AU Bu, LP Fee, E AF Bu, Liping Fee, Elizabeth TI Food hygiene and global heath SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Bu, Liping] Alma Coll, Dept Hist, Alma, MI 48801 USA. [Fee, Elizabeth] Natl Lib Med, NIH, Bethesda, MD USA. RP Bu, LP (reprint author), Alma Coll, Dept Hist, 614 W Super St, Alma, MI 48801 USA. EM bulipi@alma.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2008 VL 98 IS 4 BP 634 EP 635 DI 10.2105/AJPH.2007.124289 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 282VO UT WOS:000254595500017 PM 18309122 ER PT J AU Kitada, S Kobayashi, K Ichiyama, S Takakura, S Sakatani, M Suzuki, K Takashima, T Nagai, T Sakurabayashi, I Ito, M Maekura, R AF Kitada, Seigo Kobayashi, Kazuo Ichiyama, Satoshi Takakura, Shunij Sakatani, Mitsunori Suzuki, Katsuhiro Takashima, Tetsuya Nagai, Takayuki Sakurabayashi, Ikunosuke Ito, Masami Maekura, Ryoji CA MAC Serodiagnosis Study Grp TI Serodiagnosis of Mycobacterium avium-complex pulmonary disease using an enzyme immunoassay kit SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE nontuberculous mycobacteria; immunocompetence; sensitivity and specificity ID NONTUBERCULOUS MYCOBACTERIA; GLYCOPEPTIDOLIPID-CORE; COMPUTED-TOMOGRAPHY; UNITED-STATES; LUNG-DISEASE; TUBERCULOSIS; DIAGNOSIS; ANTIGENS; RESPONSES; COMMON AB Rationale The diagnosis of Mycobacterium avium-complex pulmonary disease (MAC-PD) and/or its discrimination from pulmonary tuberculosis (TB) is sometimes complicated and time consuming. Objectives: We investigated in a six-institution multicenter study whether a serologic test based on an enzyme immunoassay (EIA) kit was useful for diagnosing MAC-PD and for distinguishing it from other lung diseases. Methods: An EIA kit detecting serum IgA antibody to glycopeptido-lipid core antigen specific for MAC was developed. Antibody levels were measured in sera from 70 patients with MAC-PD, 18 with MAC contamination, 37 with pulmonary TB, 45 with other lung diseases, and 76 healthy subjects. Measurements and Main Results: Significantly higher serum IgA antibody levels were detected in patients with MAC-PD than in the other groups (P < 0.0001). Setting the cutoff point at 0.7 U/ml resulted in a sensitivity and specificity of the kit for diagnosing MAC-PD of 843 and 100%, respectively. Significantly higher antibody levels were also found in patients with nodular-bronchiectatic disease compared with fibrocavitary disease in MAC-PD (P < 0.05). There was a positive correlation between the extent of disease on chest computed tomography scans and the levels of antibody (r = 0.43, P < 0.05) in patients with MAC-PD. Conclusions: The EIA kit is useful for the rapid diagnosis of MAC-PD and for differentiating MAC-PD from pulmonary TB and, if validated by studies in other populations, could find wide application in clinical practice. C1 [Kitada, Seigo; Maekura, Ryoji] Natl Hosp Org Natl Toneyama, Dept Internal Med, Toyonaka, Osaka 5608552, Japan. [Kobayashi, Kazuo] NIAID, Dept Immunol, Tokyo, Japan. [Ichiyama, Satoshi; Takakura, Shunij] Kyoto Univ, Grad Sch Med, Dept Clin Lab Med, Kyoto, Japan. [Sakatani, Mitsunori; Suzuki, Katsuhiro] NHO Kinki Chuo Chest Med Ctr, Dept Internal Med, Sakai, Osaka, Japan. [Takashima, Tetsuya; Nagai, Takayuki] Osaka Prefect Med Ctr Resp & Allerg Dis, Dept Med, Habikino Shi, Osaka, Japan. [Sakurabayashi, Ikunosuke] Jich Med Univ, Saitama Med Ctr, Dept Lab Med, Saitama Shi, Japan. [Ito, Masami] Sakamoto Hosp, Dept Internal Med, Toyonaka, Osaka, Japan. RP Kitada, S (reprint author), Natl Hosp Org Natl Toneyama, Dept Internal Med, 5-1-1 Toneyama, Toyonaka, Osaka 5608552, Japan. EM kitadas@toneyama.hosp.go.jp NR 20 TC 41 Z9 41 U1 0 U2 1 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 APR 1 PY 2008 VL 177 IS 7 BP 793 EP 797 DI 10.1164/rccm.200705-771OC PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 282SI UT WOS:000254587100017 PM 18079497 ER PT J AU Solez, K Colvin, RB Racusen, LC Haas, M Sis, B Mengeld, M Halloran, PF Baldwin, W Banfi, G Collins, AB Cosio, F David, DSR Drachenberg, C Einecke, G Fogo, AB Gibson, IW Glotz, D Iskandar, SS Kraus, E Lerut, E Mannon, RB Mihatsch, M Nankivell, BJ Nickeleit, V Papadimitriou, JC Randhawa, P Regele, H Renaudin, K Roberts, I Seron, D Smith, RN Valente, M AF Solez, K. Colvin, R. B. Racusen, L. C. Haas, M. Sis, B. Mengeld, M. Halloran, P. F. Baldwin, W. Banfi, G. Collins, A. B. Cosio, F. David, D. S. R. Drachenberg, C. Einecke, G. Fogo, A. B. Gibson, I. W. Glotz, D. Iskandar, S. S. Kraus, E. Lerut, E. Mannon, R. B. Mihatsch, M. Nankivell, B. J. Nickeleit, V. Papadimitriou, J. C. Randhawa, P. Regele, H. Renaudin, K. Roberts, I. Seron, D. Smith, R. N. Valente, M. TI Banff 07 classification of renal allograft pathology: Updates and future directions SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE acute allograft rejection; acute cellular rejection; acute rejection; allograft rejection; antibody-mediated rejection; Banff; Banff lesions; Banff schema; classification; chronic allograft nephropathy; chronic allograft rejection; genomic markers; GeneChip ID ANTIBODY-MEDIATED REJECTION; CAPILLARY C4D DEPOSITION; POSITIVE CROSS-MATCH; PROTOCOL BIOPSIES; KIDNEY ALLOGRAFTS; HISTOLOGIC-FINDINGS; PERITUBULAR CAPILLARIES; SUBCLINICAL REJECTION; RISK-FACTOR; TRANSPLANTATION AB The 9th Banff Conference on Allograft Pathology was held in La Coruna, Spain on June 23-29, 2007. A total of 235 pathologists, clinicians and scientists met to address unsolved issues in transplantation and adapt the Banff schema for renal allograft rejection in response to emerging data and technologies. The outcome of the consensus discussions on renal pathology is provided in this article. Major updates from the 2007 Banff Conference were: inclusion of peritubular capillaritis grading, C4d scoring, interpretation of C4d deposition without morphological evidence of active rejection, application of the Banff criteria to zero-time and protocol biopsies and introduction of a new scoring for total interstitial inflammation (ti-score). In addition, emerging research data led to the establishment of collaborative working groups addressing issues like isolated 'v' lesion and incorporation of omics-technologies, paving the way for future combination of graft biopsy and molecular parameters within the Banff process. C1 [Solez, K.; Sis, B.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Colvin, R. B.; Collins, A. B.; Smith, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Colvin, R. B.; Collins, A. B.; Smith, R. N.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Racusen, L. C.; Haas, M.; Baldwin, W.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Sis, B.; Mengeld, M.; Halloran, P. F.; Einecke, G.] Univ Alberta, Dept Med, Div Nephrol & Immunol, Alberta Transplant Appl Genom Ctr, Edmonton, AB, Canada. [Banfi, G.] IRCCS, Fdn Osped Maggiore, Div Nephrol, Milan, Italy. [Cosio, F.] Mayo Clin & Mayo Fdn, Div Nephrol & Hypertens, Rochester, MN 55905 USA. [David, D. S. R.] Univ Sao Paulo, Div Pathol, BR-05508 Sao Paulo, Brazil. [David, D. S. R.] Univ Sao Paulo, Renal Transplant Unit, BR-05508 Sao Paulo, Brazil. [Drachenberg, C.] Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. [Fogo, A. B.] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. [Gibson, I. W.] Univ Manitoba, Dept Pathol, Winnipeg, MB R3T 2N2, Canada. [Glotz, D.] Hosp St Louis, Dept Nephrol, Paris, France. [Iskandar, S. S.] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27103 USA. [Kraus, E.] Johns Hopkins Univ, Dept Nephrol, Baltimore, MD USA. [Lerut, E.] Univ Hosp Leuven, Dept Morphol & Mol Pathol, Louvain, Belgium. [Mannon, R. B.] Natl Inst Digest & Kidney Dis, NIH, Transplantat Branch, Bethesda, MD USA. [Mihatsch, M.] Univ Basel, Inst Pathol, Basel, Switzerland. [Nankivell, B. J.] Westmead Hosp, Ctr Transplant Res & Renal Res, Sydney, NSW, Australia. [Nickeleit, V.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Randhawa, P.] Univ Pittsburgh, Dept Pathol, Div Transplantat Pathol, Pittsburgh, PA USA. [Regele, H.] Univ Vienna, Inst Pathol, A-1010 Vienna, Austria. [Renaudin, K.] CHU Hotel Dieu, Dept Pathol, Nantes, France. [Roberts, I.] John Radcliffe Hosp, Dept Cellular Pathol, Oxford OX3 9DU, England. [Seron, D.] Univ Bellvitge, Dept Nephrol, Barcelona, Spain. [Valente, M.] Univ Padua, Dept Med Diag Sci, Padua, Italy. RP Solez, K (reprint author), Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. EM Kim.Solez@ualberta.ca RI Glotz, Denis/F-7881-2011; David, Daisa/G-6272-2012; Halloran, Philip/J-1390-2012; OI Halloran, Philip/0000-0003-1371-1947; Valente, Marialuisa/0000-0002-3662-2878 NR 40 TC 1039 Z9 1108 U1 4 U2 28 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2008 VL 8 IS 4 BP 753 EP 760 DI 10.1111/j.1600-6143.2008.02159.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 270YW UT WOS:000253757100007 PM 18294345 ER PT J AU Schneeberger, S Hautz, T Wahl, SM Brandacher, G Sucher, R Steinmassl, O Steinmassl, P Wright, CD Obrist, P Werner, ER Mark, W Troppmair, J Margreiter, R Amberger, A AF Schneeberger, S. Hautz, T. Wahl, S. M. Brandacher, G. Sucher, R. Steinmassl, O. Steinmassl, P. Wright, C. D. Obrist, P. Werner, E. R. Mark, W. Troppmair, J. Margreiter, R. Amberger, A. TI The effect of secretory leukocyte protease inhibitor (SLPI) on ischemia/reperfusion injury in cardiac transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE heart transplantation; ischemia; reperfusion; SLPI ID GROWTH-FACTOR-BETA; PROLONGED COLD ISCHEMIA; MYOCARDIAL-INFARCTION; HEART-TRANSPLANTATION; POTENT INHIBITOR; INFLAMMATORY RESPONSES; ELASTASE INHIBITOR; REPERFUSION INJURY; RAT; EXPRESSION AB We investigated the role of secretory leukocyte protease inhibitor (SLPI) in ischemia/reperfusion injury in cardiac transplantation. SLPI-/- mouse hearts and wild-type (WT) controls were transplanted immediately or after 10 h of cold ischemia (CI). Recombinant SLPI (rSLPI) was added to the preservation solution or given systemically. After evaluation of myocardial performance, grafts were investigated for histology, SLPI, TNF-alpha, TGF-beta, NF-kappa B and protease expression at indicated time points. Early myocardial contraction was profoundly impaired in SLPI-/- hearts exposed to CI and associated with high intra-graft protease expression. Systemic administration of rSLPI had no effect, however, when SLPI was added to the preservation solution, myocardial contraction was restored to normal. At 10 days, inflammation, myocyte vacuolization and necrosis were significantly more severe in SLPI-/- hearts. SLPI gene expression was detected in WT mice at 12 and 24 h and was significantly higher after CI. SLPI protein was observed at 24 h and 10 days. High intra-graft concentrations of SLPI after administration of rSLPI were inversely correlated with protease levels early and TGF-beta expression late after reperfusion. SLPI plays a crucial role in early myocardial performance and postischemic inflammation after cardiac transplantation. A dual inhibitory effect on protease and TGF-beta expression might be the underlying mechanism. C1 [Schneeberger, S.; Hautz, T.; Brandacher, G.; Sucher, R.; Steinmassl, O.; Steinmassl, P.; Mark, W.; Troppmair, J.; Margreiter, R.] Innsbruck Med Univ, Dept Gen & Transplant Surg, D Swarovski Res Lab, Innsbruck, Austria. [Wahl, S. M.] Natl Inst Dental & Craniofacial Res, Oral Infect & Immun Branch, Bethesda, MD USA. [Wright, C. D.] Amgen Inc, Dept Inflammat Res, Seattle, WA USA. [Obrist, P.] St Vincenz Hosp Zams, Dept Pathol, Zams, Austria. [Werner, E. R.] Innsbruck Med Univ, Div Biol Chem, Bioctr, Innsbruck, Austria. [Amberger, A.] Innsbruck Med Univ, Tyrolean Canc Res Inst, Innsbruck, Austria. RP Schneeberger, S (reprint author), Innsbruck Med Univ, Dept Gen & Transplant Surg, D Swarovski Res Lab, Innsbruck, Austria. EM schneebergers@upmc.edu RI Brandacher, Gerald/L-7540-2016; OI Werner, Ernst R./0000-0003-1948-3391 NR 34 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2008 VL 8 IS 4 BP 773 EP 782 DI 10.1111/j.1600-6143.2008.02158.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 270YW UT WOS:000253757100009 PM 18294346 ER PT J AU Frances, SP Baade, LM Kubofcik, J Nutman, TB Melrose, WD McCarthy, JS Nissen, MD AF Frances, Stephen P. Baade, Lisa M. Kubofcik, Joseph Nutman, Thomas B. Melrose, Wayne D. McCarthy, James S. Nissen, Michael D. TI Seroconversion to filarial antigens in Australian defence force personnel in Timor-Leste SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID LYMPHATIC FILARIASIS; BRUGIA-TIMORI; WUCHERERIA-BANCROFTI; ANTIBODIES; INFECTION; INDONESIA; VIETNAM; DISEASE; ISLAND AB To investigate whether Australian soldiers were exposed to filarial parasites that cause lymphatic filariasis during a 6-month deployment to Timor-Leste, antifilarial antibody levels were measured in 907 soldiers using an enzyme linked immunosorbent assay (ELISA). Initial testing using Dirofilaria immitis antigen demonstrated that 49 of 907 (5.4%) soldiers developed antifilarial antibodies of the IgG1 subclass after deployment, whereas 1 of 944 (0.1%) seroconverted to the IgG4 subclass. When a sub sample of 88 D. immitis-reactive sera was subject to testing with an antifilarial antibody test using Brugia malayi antigen, 46 had elevated IgG antibodies, whereas 5 had elevated antibodies of the IgG4 subclass. A total of 24 soldiers seroconverted to B. malayi, as measured by parasite-specific IgG, whereas 1 seroconverted to IgG4. The relatively low number of seroconversions indicates a low but measurable risk of exposure to human filarial parasites among Australian soldiers deployed to Timor-Leste. However, to reduce the risk of exposure to these parasites, soldiers deploying to endemic areas should practice strict adherence to personal protective measures against mosquito bites. C1 [Frances, Stephen P.] Australian Army Malaria Inst, Brisbane, Qld 4051, Australia. NIH, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. James Cook Univ N Queensland, Sch Publ Hlth & Trop Med, Lymphat Filariasis Support Ctr, Townsville, Qld 4811, Australia. Univ Queensland, Royal Brisbane Hosp, Australian Ctr Int & Trop Hlth, Sch Med, Herston, Qld, Australia. Univ Queensland, Queensland Inst Med Res, Herston, Qld, Australia. Royal Brisbane & Womens Hosp, Herston, Qld, Australia. RP Frances, SP (reprint author), Australian Army Malaria Inst, Brisbane, Qld 4051, Australia. EM steve.frances@defence.gov.au RI Nissen, Michael/M-6823-2013 OI Nissen, Michael/0000-0003-1686-3313 NR 22 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2008 VL 78 IS 4 BP 560 EP 563 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 287UZ UT WOS:000254943300009 PM 18385349 ER PT J AU Hoffert, JD Knepper, MA AF Hoffert, Jason D. Knepper, Mark A. TI Taking aim at shotgun phosphoproteomics SO ANALYTICAL BIOCHEMISTRY LA English DT Review ID ELECTRON-TRANSFER DISSOCIATION; TANDEM MASS-SPECTROMETRY; DECOY SEARCH STRATEGY; SACCHAROMYCES-CEREVISIAE; QUANTITATIVE PHOSPHOPROTEOMICS; TYROSINE PHOSPHORYLATION; PROTEIN IDENTIFICATION; PEPTIDE IDENTIFICATION; SIGNALING NETWORKS; PROTEOMIC ANALYSIS C1 [Hoffert, Jason D.; Knepper, Mark A.] NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Hoffert, JD (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, Bldg 10, Bethesda, MD 20892 USA. EM hoffertj@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21]; NHLBI NIH HHS [Z01 HL001285] NR 55 TC 35 Z9 37 U1 3 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 1 PY 2008 VL 375 IS 1 BP 1 EP 10 DI 10.1016/j.ab.2007.11.023 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 275GO UT WOS:000254060100001 PM 18078798 ER PT J AU Simeonov, A Yasgar, A Jadhav, A Lokesh, GL Klumpp, C Michael, S Austin, CP Natarajan, A Inglese, J AF Simeonov, Anton Yasgar, Adam Jadhav, Ajit Lokesh, G. L. Klumpp, Carleen Michael, Sam Austin, Christopher P. Natarajan, Amarnath Inglese, James TI Dual-fluorophore quantitative high-throughput screen for inhibitors of BRCT-phosplioprotein interaction SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE quantitative high-throughput screening; BRCT; pBACH1; fluorescence polarization assay; hotspot interaction; 1536-Well plate ID DNA-DAMAGE RESPONSE; SMALL-MOLECULE INHIBITORS; CYCLE CHECKPOINT CONTROL; STRUCTURAL BASIS; PHOSPHOPEPTIDE RECOGNITION; STATISTICAL PARAMETER; BACH1 PHOSPHOPEPTIDE; TARGETS BRCA1; HOT-SPOTS; PROTEIN AB Finding specific small-molecule inhibitors of protein-protein interactions remains a significant challenge. Recently, attention has grown toward "hot spot" interactions where binding is dominated by a limited number of amino acid contacts, theoretically offering an increased opportunity for disruption by small molecules. Inhibitors of the interaction between BRCT (the C-terminal portion of BRCA1, a key tumor suppressor protein with various functions) and phosphorylated proteins (Abraxas/BACH1/CtIP), implicated in DNA damage response and repair pathways, should prove to be useful in studying BRCA1's role in cancer and in potentially sensitizing tumors to chemotherapeutic agents. We developed and miniaturized to a 1536-well format and 3-mu l final volume a pair of fluorescence polarization (FP) assays using fluorescein- and rhodamine-labeled pBACH1 fragment. To minimize the effect of fluorescence artifacts and to increase the overall robustness of the screen, the 75,552 compound library members all were assayed against both the fluorescein- and rhodamine-labeled probe-protein complexes in separate but interleaved reactions. In addition, every library compound was tested over a range of concentrations following the quantitative high-throughput screening (qHTS) paradigm. Analyses of the screening results led to the selection and subsequent confirmation of 16 compounds active in both assays. Faced with a traditionally difficult protein-protein interaction assay, by performing two-fluorophore qHTS, we were able to confidently select a number of actives for further studies. (c) 2007 Elsevier Inc. All rights reserved. C1 [Simeonov, Anton; Yasgar, Adam; Jadhav, Ajit; Klumpp, Carleen; Michael, Sam; Austin, Christopher P.; Inglese, James] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Lokesh, G. L.; Natarajan, Amarnath] Univ Texas Galveston, Med Branch, Dept Pharmacol & Toxicol, Chem Biol Program, Galveston, TX 77555 USA. RP Natarajan, A (reprint author), NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. EM amnatara@utmb.edu; jinglese@mail.nih.gov FU Intramural NIH HHS [ZIB HG200319-07, Z01 HG200319-04, ZIA HG200319-06, Z01 HG200319-05] NR 38 TC 26 Z9 26 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 1 PY 2008 VL 375 IS 1 BP 60 EP 70 DI 10.1016/j.ab.2007.11.039 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 275GO UT WOS:000254060100008 PM 18158907 ER PT J AU Culver, M Hedrick, PW Murphy, K O'Brien, S Hornocker, MG AF Culver, M. Hedrick, P. W. Murphy, K. O'Brien, S. Hornocker, M. G. TI Estimation of the bottleneck size in Florida panthers SO ANIMAL CONSERVATION LA English DT Article DE computer simulation; effective population size; endangered species; microsatellite loci; mtDNA ID GENETIC RESTORATION AB We have estimated the extent of genetic variation in museum (1890s) and contemporary (1980s) samples of Florida panthers Puma concolor coryi for both nuclear loci and mtDNA. The microsatellite heterozygosity in the contemporary sample was only 0.325 that in the museum samples although our sample size and number of loci are limited. Support for this estimate is provided by a sample of 84 microsatellite loci in contemporary Florida panthers and Idaho pumas Puma concolor hippolestes in which the contemporary Florida panther sample had only 0.442 the heterozygosity of Idaho pumas. The estimated diversities in mtDNA in the museum and contemporary samples were 0.600 and 0.000, respectively. Using a population genetics approach, we have estimated that to reduce either the microsatellite heterozygosity or the mtDNA diversity this much (in a period of c. 80 years during the 20th century when the numbers were thought to be low) that a very small bottleneck size of c. 2 for several generations and a small effective population size in other generations is necessary. Using demographic data from Yellowstone pumas, we estimated the ratio of effective to census population size to be 0.315. Using this ratio, the census population size in the Florida panthers necessary to explain the loss of microsatellite variation was c. 41 for the non-bottleneck generations and 6.2 for the two bottleneck generations. These low bottleneck population sizes and the concomitant reduced effectiveness of selection are probably responsible for the high frequency of several detrimental traits in Florida panthers, namely undescended testicles and poor sperm quality. The recent intensive monitoring both before and after the introduction of Texas pumas in 1995 will make the recovery and genetic restoration of Florida panthers a classic study of an endangered species. Our estimates of the bottleneck size responsible for the loss of genetic variation in the Florida panther completes an unknown aspect of this account. C1 [Hedrick, P. W.] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. [Culver, M.; O'Brien, S.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Murphy, K.] Natl Pk Serv, Yellowstone Natl Pk, WY USA. RP Hedrick, PW (reprint author), Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA. EM philip.hedrick@asu.edu NR 21 TC 17 Z9 17 U1 3 U2 59 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1367-9430 J9 ANIM CONSERV JI Anim. Conserv. PD APR PY 2008 VL 11 IS 2 BP 104 EP 110 DI 10.1111/j.1469-1795.2007.00154.x PG 7 WC Biodiversity Conservation; Ecology SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 281LJ UT WOS:000254498700004 ER PT J AU Ianella, P Venancio, LPR Stafuzza, NB Miziara, MN Agarwala, R Schaffer, AA Riggs, PK Womack, JE Amaral, MEJ AF Ianella, P. Venancio, L. P. R. Stafuzza, N. B. Miziara, M. N. Agarwala, R. Schaffer, A. A. Riggs, P. K. Womack, J. E. Amaral, M. E. J. TI First radiation hybrid map of the river buffalo X chromosome (BBUX) and comparison with BTAX SO ANIMAL GENETICS LA English DT Article DE radiation hybrid mapping; river buffalo; X chromosome ID BUBALUS-BUBALIS; GENOME SEQUENCE; CATTLE; SHEEP; GOAT; MICROSATELLITES; DIVERGENCES; HOMOLOGIES; 2N=50 AB We report the first radiation hybrid map of the river buffalo X chromosome generated from a recently constructed river buffalo (Bubalus bubalis) whole-genome radiation hybrid panel (BBURH5000). This map contains a total of 33 cattle-derived markers, including 10 genes, four ESTs and 19 microsatellites. The markers are distributed in two linkage groups: LG1 contains eight markers spanning 125.6 cR, and LG2 contains 25 markers spanning 366.3 cR. LG1 contains six markers in common with bovine sequence assembly BUILD 3.1. With the exception of BMS2152, the order of these markers on our BBUX map is shuffled when compared to the cow X chromosome (Bos taurus; BTAX). From LG2, two markers (AMELX and BL22) map to a more distal portion of BTAX compared to BBUX. In addition, two pairs of LG2 markers exhibit inversions compared to BTAX (ILSTS017 and ATRX; XBM38 and PPEF1). Alternatively, when compared to the most recent bovine RH map (Bov-Gen 3000rads), BL1098 and BMS2227 from LG1 as well as PLS3 and BMS1820 from LG2 showed inverted positions on the BBUX map. These discrepancies in buffalo and cattle maps may reflect evolutionary divergence of the chromosomes or mapping errors in one of the two species. Although the set of mapped markers does not cover the entire X chromosome, this map is a starting point for the construction of a high-resolution map, which is necessary for characterization of small rearrangements that might have occurred between the Bubalus bubalis and Bos taurus X chromosomes. C1 [Womack, J. E.; Amaral, M. E. J.] Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX 77843 USA. [Ianella, P.; Venancio, L. P. R.; Stafuzza, N. B.; Miziara, M. N.; Amaral, M. E. J.] Sao Paulo State Univ, Dept Biol, IBILCE, UNESP, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil. [Agarwala, R.; Schaffer, A. A.] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. [Riggs, P. K.] Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA. [Womack, J. E.; Amaral, M. E. J.] Texas A&M Univ, Dept Vet Pathobiol, Coll Sci, College Stn, TX 77843 USA. RP Amaral, MEJ (reprint author), Texas A&M Univ, Dept Vet Pathobiol, Vet Med Res Bldg 1197,Raymond Stotzer Pkway, College Stn, TX 77843 USA. EM eamaral@cvm.tamu.edu RI Riggs, Penny/A-8192-2008; Venancio, Larissa /D-5683-2012; Schaffer, Alejandro/F-2902-2012; Amaral, Elisabete/K-9246-2013; Ianella, Patricia/A-2444-2016; Stafuzza, Nedenia/C-4419-2013 OI Riggs, Penny/0000-0003-3296-320X; Ianella, Patricia/0000-0002-6651-2987; Stafuzza, Nedenia/0000-0001-6432-2330 FU Intramural NIH HHS NR 19 TC 7 Z9 7 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0268-9146 J9 ANIM GENET JI Anim. Genet. PD APR PY 2008 VL 39 IS 2 BP 196 EP 200 DI 10.1111/j.1365-2052.2007.01696.x PG 5 WC Agriculture, Dairy & Animal Science; Genetics & Heredity SC Agriculture; Genetics & Heredity GA 279US UT WOS:000254381100014 PM 18307583 ER PT J AU Stratakis, CA Horvath, A AF Stratakis, C. A. Horvath, A. TI How the new tools to analyze human genome are opening new perspectives: The use of gene expression in investigations of the adrenal cortex SO ANNALES D ENDOCRINOLOGIE LA English DT Article DE adrenal cortex; microarrays; serial analysis of gene expression (SAGE); oligonucleotides; complementary DNA (cDNA); messenger RNA (mRNA); gene expression; adrenal hyperplasia ID NODULAR ADRENOCORTICAL DISEASE; GROWTH-FACTOR RECEPTOR; SUBUNIT TYPE 1A; CUSHINGS-SYNDROME; CARNEY COMPLEX; HUMAN-FETAL; REGULATORY SUBUNIT; MACRONODULAR HYPERPLASIA; STEROIDOGENIC ENZYMES; LUTEINIZING-HORMONE AB With the promise of state-of-the-art molecular technologies and the tools provided by the human genome project, a number of investigators are trying to identify molecular targets of adrenocortical tumorigenesis. One path in this endeavor was the identification by positional cloning of genes that are mutated in rare adrenocortical tumors. The subject of this article is an update of the results of experiments in the second path that was followed by us and others: that of using genome-wide expression analysis of adrenocortical cells in normal and various disease states. Transcriptomic analysis is a rapidly evolving technology; this article summarizes some data on the adrenal cortex and points out how these new technologies can be used in the identification of important genes and molecular pathways in both normal and diseased adrenal cortex. Published by Elsevier Masson SAS C1 [Stratakis, C. A.; Horvath, A.] NICHHD, Endocrinol Sect, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Endocrinol Sect, Program Dev Endocrinol & Genet, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 54 TC 1 Z9 1 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0003-4266 J9 ANN ENDOCRINOL-PARIS JI Ann Endocrinol. PD APR PY 2008 VL 69 IS 2 BP 123 EP 129 DI 10.1016/j.ando.2008.02.009 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 307IY UT WOS:000256313800007 PM 18423555 ER PT J AU Friedlander, SL Dooms, KT Seroogy, CM Voss, CY Agger, WA Zhang, K Bleesing, J Filipovich, AH AF Friedlander, Samuel L. Dooms, Kevin T. Seroogy, Christine M. Voss, Ching Y. Agger, William A. Zhang, Kejian Bleesing, Jack Filipovich, Alexandra H. TI Adolescent presentation of X-linked lymphoproliferative disease SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID BARR-VIRUS INFECTION C1 [Friedlander, Samuel L.; Dooms, Kevin T.; Seroogy, Christine M.] Univ Wisconsin, Div Rheumatol Allergy & Immunol, Madison, WI 53706 USA. [Voss, Ching Y.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Agger, William A.] Gundersen Lutheran Med Fdn, Infect Dis Sect, La Crosse, WI USA. [Zhang, Kejian; Bleesing, Jack; Filipovich, Alexandra H.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. RP Friedlander, SL (reprint author), Univ Wisconsin, Div Rheumatol Allergy & Immunol, Madison, WI 53706 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD APR PY 2008 VL 100 IS 4 BP 398 EP 400 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 284LB UT WOS:000254706800021 PM 18450131 ER PT J AU Resnicow, K Davis, RE Zhang, G Konkel, J Strecher, VJ Shaikh, AR Tolsma, D Calvi, J Alexander, G Anderson, JP Wiese, C AF Resnicow, Ken Davis, Rachel E. Zhang, Guangyu Konkel, Janine Strecher, Victor J. Shaikh, Abdul R. Tolsma, Dennis Calvi, Josephine Alexander, Gwen Anderson, Julia P. Wiese, Cheryl TI Tailoring a fruit and vegetable intervention on novel motivational constructs: Results of a randomized study SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE self -determination theory; tailored intervention; public health ID AFRICAN-AMERICAN CHURCHES; SELF-DETERMINATION THEORY; SMOKING-CESSATION; NUTRITION EDUCATION; HEALTH COMMUNICATION; PHYSICAL-ACTIVITY; TRIAL; MESSAGES; BEHAVIOR; IMPACT AB Background Tailored health communications to date have been based on a rather narrow set of theoretical constructs. Purpose This study was designed to test whether tailoring a print-based fruit and vegetable (F & V) intervention on relatively novel constructs from self-determination theory (SDT) and motivational interviewing (MI) increases intervention impact, perceived relevance, and program satisfaction. The study also aimed to explore possible user characteristics that may moderate intervention response. Methods African American adults were recruited from two integrated health care delivery systems, one based in the Detroit Metro area and the other in the Atlanta Metro area, and then randomized to receive three tailored newsletters over 3 months. One set of newsletters was tailored only on demographic and social cognitive variables (control condition), whereas the other (experimental condition) was tailored on SDT and MI principles and strategies. The primary focus of the newsletters and the primary outcome for the study was fruit and vegetable intake assessed with two brief self-report measures. Preference for autonomy support was assessed at baseline with a single item: "In general, when it comes to my health I would rather an expert just tell me what I should do". Most between-group differences were examined using change scores. Results A total of 512 (31%) eligible participants, of 1,650 invited, were enrolled, of which 423 provided complete 3-month follow-up data. Considering the entire sample, there were no significant between-group differences in daily F & V intake at 3 month follow-up. Both groups showed similar increases of around one serving per day of F & V on the short form and half a serving per day on the long form. There were, however, significant interactions of intervention group with preference for autonomy-supportive communication as well as with age. Specifically, individuals in the experimental intervention who, at baseline, preferred an autonomy-supportive style of communication increased their F & V intake by 1.07 servings compared to 0.43 servings among controls. Among younger controls, there was a larger change in F & V intake, 0.59 servings, than their experimental group counterparts, 0.29 servings. Conversely, older experimental group participants showed a larger change in F & V, 1.09 servings, than older controls, 0.48. Conclusion Our study confirms the importance of assessing individual differences as potential moderators of tailored health interventions. For those who prefer an autonomy-supportive style of communication, tailoring on values and other motivational constructs can enhance message impact and perceived relevance. C1 [Resnicow, Ken; Davis, Rachel E.; Zhang, Guangyu; Konkel, Janine; Strecher, Victor J.] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Shaikh, Abdul R.] NCI, Bethesda, MD 20892 USA. [Tolsma, Dennis; Calvi, Josephine] Kaiser Permanente Georgia, Ctr Hlth Res SE, Atlanta, GA USA. [Alexander, Gwen] Henry Ford Hosp, Detroit, MI 48202 USA. [Anderson, Julia P.; Wiese, Cheryl] Ctr Hlth Studies Grp Hlth, Seattle, WA USA. RP Resnicow, K (reprint author), Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, 109 Observ St,Room 3867 SPH I, Ann Arbor, MI 48109 USA. EM kresnic@umich.edu OI Tolsma, Dennis/0000-0002-0685-0618 FU NCI NIH HHS [P50 CA101451] NR 53 TC 59 Z9 59 U1 4 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2008 VL 35 IS 2 BP 159 EP 169 DI 10.1007/s12160-008-9028-9 PG 11 WC Psychology, Multidisciplinary SC Psychology GA 289MC UT WOS:000255057600004 PM 18401673 ER PT J AU Loomba, R Rowley, A Wesley, R Liang, TJ Hoofnagle, JH Pucino, F Csako, G AF Loomba, Rohit Rowley, Ayana Wesley, Robert Liang, T. Jake Hoofnagle, Jay H. Pucino, Frank Csako, Gyorgy TI Systematic review: The effect of preventive lamivudine on hepatitis B reactivation during chemotherapy SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID BREAST-CANCER PATIENTS; VIRUS REACTIVATION; CYTOTOXIC CHEMOTHERAPY; PREEMPTIVE LAMIVUDINE; PROPHYLAXIS; THERAPY; INFECTION; CARRIERS; LYMPHOMA; DISEASE AB Background: Lamivudine is increasingly being used to prevent hepatitis B reactivation in patients with cancer who test positive for hepatitis B surface antigen (HBsAg) and are undergoing chemotherapy. Purpose: To determine whether preventive lamivudine reduces chemotherapy-induced hepatitis B virus (HBV)-related morbidity and mortality in patients with cancer who test positive for HBsAg. Data Sources: MEDLINE, Ovid MEDLINE, TOXNET, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched in all languages until June 2007. Study Selection: Clinical trials and cohort studies that reported the efficacy of preventive lamivudine versus control on HBV reactivation in patients who tested positive for HBsAg and were receiving chemotherapy were included. Additional requirements included minimum sample size (>5 participants per treatment group) and reported HBV-related morbidity and mortality data. Data Extraction: Two investigators independently did literature searches and data extraction, and 2 other investigators independently confirmed study eligibility and data retrieval. Data Synthesis: Fourteen studies (2 randomized, controlled trials; 8 prospective cohort studies; and 4 retrospective cohort studies) met the predefined criteria for analysis. There were 275 patients in the preventive lamivudine group and 475 control participants for the primary end point of HBV reactivation. With preventive lamivudine, the relative risk for both HBV reactivation and HBV-related hepatitis ranged from 0.00 to 0.21. None of the patients in the preventive lamivudine group developed HBV-related hepatic failure (0 of 108 patients vs. 21 of 162 patients), and only 4 deaths were attributable to HBV (4 of 208 patients vs. 27 of 394 patients) in the preventive lamivudine group. Lamivudine was well tolerated, and no adverse effects were noted. Limitations: The studies included in the meta-analysis did not consistently report all of the outcomes of interest. Sample sizes were small and only 2 studies had a randomized, controlled design. Conclusion: Preventive therapy with lamivudine for patients who test positive for HBsAg and are undergoing chemotherapy may reduce the risk for HBV reactivation and HBV-associated morbidity and mortality. C1 [Loomba, Rohit; Rowley, Ayana; Wesley, Robert; Liang, T. Jake; Hoofnagle, Jay H.; Pucino, Frank; Csako, Gyorgy] US Dept HHS, Natl Inst Hlth, Bethesda, MD USA. RP Loomba, R (reprint author), NIDDKD, NIH, CRC-4-5722,MSC-1614,10 Ctr Dr, Bethesda, MD 20892 USA. EM roloomba@ucsd.edu FU Intramural NIH HHS [Z01 DK054501-11] NR 35 TC 226 Z9 248 U1 1 U2 12 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 APR 1 PY 2008 VL 148 IS 7 BP 519 EP 528 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 284IV UT WOS:000254701000004 PM 18378948 ER PT J AU Hines, CJ Deddens, JA Jaycox, LB Andrews, RN Striley, CAF Alavanja, MCR AF Hines, Cynthia J. Deddens, James A. Jaycox, Larry B. Andrews, Ronnee N. Striley, Cynthia A. F. Alavanja, Michael C. R. TI Captan exposure and evaluation of a pesticide exposure algorithm among orchard pesticide applicators in the agricultural health study SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE agriculture; benomyl; captan; exposure assessment; fungicide; occupational; orchard; pesticide; thiophanate-methyl ID RETINAL DEGENERATION; FLORIDA CITRUS; WORKER REENTRY; TETRAHYDROPHTALIMIDE; CALIFORNIA; CREATININE; HUMANS; URINE; THPI; ACID AB Pesticide exposure assessment in the Agricultural Health Study (AHS) has relied upon two exposure metrics: lifetime exposure days and intensity-weighted lifetime exposure days, the latter incorporating an intensity score computed from a questionnaire-based algorithm. We evaluated this algorithm using actual fungicide exposure measurements from AHS private orchard applicators. Captan was selected as a marker of fungicide exposure. Seventy-four applicators from North Carolina and Iowa growing apples and/or peaches were sampled on 2 days they applied captan in 2002 and 2003. Personal air, hand rinse, 10 dermal patches, a pre-application first-morning urine and a subsequent 24-h urine sample were collected from each applicator per day. Environmental samples were analyzed for captan, and urine samples were analyzed for cis-1,2,3,6-tetrahydrophthalimide (THPI). Task and personal protective equipment information needed to compute an individual's algorithm score was also collected. Differences in analyte detection frequency were tested in a repeated logistic regression model. Mixed-effects models using maximum-likelihood estimation were employed to estimate geometric mean exposures and to evaluate the measured exposure data against the algorithm. In general, captan and THPI were detected significantly more frequently in environmental and urine samples collected from applicators who used air blast sprayers as compared to those who hand sprayed. The AHS pesticide exposure intensity algorithm, while significantly or marginally predictive of thigh and forearm captan exposure, respectively, did not predict air, hand rinse or urinary THPI exposures. The algorithm's lack of fit with some exposure measures among orchard fungicide applicators may be due in part to the assignment of equal exposure weights to air blast and hand spray application methods in the current algorithm. Some modification of the algorithm is suggested by these results. C1 [Hines, Cynthia J.; Deddens, James A.; Jaycox, Larry B.; Andrews, Ronnee N.; Striley, Cynthia A. F.] NIOSH, Cincinnati, OH 45226 USA. [Deddens, James A.] Univ Cincinnati, Dept Math Sci, Cincinnati, OH 45221 USA. [Alavanja, Michael C. R.] NCI, Bethesda, MD 20892 USA. RP Hines, CJ (reprint author), NIOSH, 4676 Columbia Pkwy R-14, Cincinnati, OH 45226 USA. EM chines@cde.gov NR 33 TC 24 Z9 24 U1 3 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0003-4878 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD APR PY 2008 VL 52 IS 3 BP 153 EP 166 DI 10.1093/annhyg/men001 PG 14 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 286WS UT WOS:000254877300002 PM 18326518 ER PT J AU Sawalha, AH Kaufman, KM Kelly, JA Adler, AJ Aberle, T Kilpatrick, J Wakeland, EK Li, QZ Wandstrat, AE Karp, DR James, JA Merrill, JT Lipsky, P Harley, JB AF Sawalha, A. H. Kaufman, K. M. Kelly, J. A. Adler, A. J. Aberle, T. Kilpatrick, J. Wakeland, E. K. Li, Q-Z Wandstrat, A. E. Karp, D. R. James, J. A. Merrill, J. T. Lipsky, P. Harley, J. B. TI Genetic association of interleukin-21 polymorphisms with systemic lupus erythematosus SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID B-CELLS; IL-21 RECEPTOR; CUTTING EDGE; T-CELLS; DIFFERENTIATION; CHAIN AB Objective: The aetiology of systemic lupus erythematosus (SLE) is incompletely understood. Both genetic and environmental factors are implicated in the pathogenesis of the disease. Herein, we describe genetic association between SLE and polymorphisms in the interleukin (IL)-21 gene. The reported effect of IL-21 on B-cell differentiation into plasma cells and its effect on dendritic cell maturation and T-cell responses make IL-21 an attractive candidate gene for SLE. Methods: Three single nucleotide polymorphisms (SNPs) in the IL-21 gene were genotyped in a total of 2636 individuals (1318 cases and 1318 controls matched for age, sex and race). Population-based case-control association analyses were performed. Results: We found a genetic association with SLE and two SNPs located within the IL-21 gene (rs907715: chi(2) = 11.55, p<0.001; rs2221903: chi(2) = 5.49, p = 0.019). Furthermore, genotypes homozygous for the risk alleles were more frequent than genotypes homozygous for the non-risk alleles in European-American patients as compared to controls (rs907715 (GG versus AA): odds ratio (OR)= 1.66, p = 0.0049; rs2221903 (GG versus AA): OR = 1.60, p = 0.025). Conclusion: Our findings indicate that IL-21 polymorphism is a candidate association with SLE. The functional effects of this association, when revealed, might improve our understanding of the disease and provide new therapeutic targets. C1 [Sawalha, A. H.; Kaufman, K. M.; Harley, J. B.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Sawalha, A. H.; Kaufman, K. M.; Merrill, J. T.; Harley, J. B.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Sawalha, A. H.; Kaufman, K. M.; Kelly, J. A.; Adler, A. J.; Aberle, T.; Kilpatrick, J.; James, J. A.; Merrill, J. T.; Harley, J. B.] Oklahoma Med Res Fdn, Arthritis & Immunol Program, Oklahoma City, OK 73104 USA. [Wakeland, E. K.; Li, Q-Z; Wandstrat, A. E.] Univ Texas SW Med Ctr Dallas, Ctr Immunol, Dallas, TX 75390 USA. [Karp, D. R.] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA. [Lipsky, P.] NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA. RP Sawalha, AH (reprint author), 825 NE 13th St,MS 24, Oklahoma City, OK 73104 USA. EM amr-sawalha@omrf.ouhsc.edu FU NCRR NIH HHS [RR020143, P20-RR015577]; NIAID NIH HHS [AI31584, AI24717, AI053747]; NIAMS NIH HHS [AR4894, AR42460, AR12253, P30 AR053483] NR 19 TC 113 Z9 120 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD APR PY 2008 VL 67 IS 4 BP 458 EP 461 DI 10.1136/ard.2007.075424 PG 4 WC Rheumatology SC Rheumatology GA 276DI UT WOS:000254121100006 PM 17720724 ER PT J AU Chaturvedi, V Ramani, R Ghannoum, MA Killian, SB Holliday, N Knapp, C Ostrosky-Zeichner, L Messer, SA Pfaller, MA Iqbal, NJ Arthington-Skaggs, BA Vazquez, JA Sein, T Rex, JH Walsh, TJ AF Chaturvedi, Vishnu Ramani, Rama Ghannoum, Mahmoud A. Killian, Scott B. Holliday, Nicole Knapp, Cindy Ostrosky-Zeichner, Luis Messer, Shawn A. Pfaller, Michael A. Iqbal, Naureen J. Arthington-Skaggs, Beth A. Vazquez, Jose A. Sein, Tin Rex, John H. Walsh, Thomas J. TI Multilaboratory testing of antifungal combinations against a quality control isolate of Candida krusei SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID TIME-KILL; CLINICAL-EFFICACY; AGENTS; FLUCONAZOLE; THERAPY; VORICONAZOLE; TERBINAFINE; CASPOFUNGIN; ANTAGONISM; SYNERGY AB Candida krusei ATCC 6258 was tested by eight laboratories using 96-well plates containing checkerboard pairwise combinations of amphotericin B (AMB), posaconazole (PSC), caspofungin (CSP), and voriconazole (VRC). The methodology led to reproducible results across the laboratories. All drug combinations yielded MICs lower than the MICs of any two drugs tested singly, and combinations of AMB, PSC, CSP, and VRC were indifferent (no antagonism) by summations of fractional inhibitory concentration. C1 [Chaturvedi, Vishnu; Ramani, Rama] New York State Dept Hlth, Wadsworth Ctr, Mycol Lab, Albany, NY 12208 USA. [Ghannoum, Mahmoud A.] Case Western Reserve Univ, Ctr Med Mycol, Cleveland, OH 44106 USA. [Killian, Scott B.; Holliday, Nicole; Knapp, Cindy] TREK Diagnost Syst, Cleveland, OH USA. [Ostrosky-Zeichner, Luis] Univ Texas Houston, Houston, TX USA. [Pfaller, Michael A.] Univ Iowa, Iowa City, IA USA. [Iqbal, Naureen J.; Arthington-Skaggs, Beth A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Vazquez, Jose A.] Wayne State Univ, Detroit, MI USA. [Sein, Tin; Walsh, Thomas J.] NCI, Bethesda, MD 20892 USA. RP Chaturvedi, V (reprint author), New York State Dept Hlth, Wadsworth Ctr, Mycol Lab, 120 New Scotland Ave, Albany, NY 12208 USA. EM vishnu@wadsworth.org NR 18 TC 15 Z9 16 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2008 VL 52 IS 4 BP 1500 EP 1502 DI 10.1128/AAC.00574-07 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 286YE UT WOS:000254881900041 PM 18227180 ER PT J AU Minetti, M Leto, TL Malorni, W AF Minetti, Maurizio Leto, Thomas L. Malorni, Walter TI Radical generation and alterations of erythrocyte integrity as bioindicators of diagnostic or prognostic value in COPD? SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; EXHALED NITRIC-OXIDE; RED-BLOOD-CELL; OXIDATIVE STRESS; HOST-DEFENSE; FUNCTIONAL-ACTIVITY; CIGARETTE-SMOKING; RESPIRATORY-TRACT; PROTEIN OXIDATION; HEALTHY SMOKERS AB Chronic obstructive pulmonary disease (COPD) has recently been viewed as an inflammation-dependent systemic disease. Oxidative modifications in the pulmonary microenvironment can result in a number of functional changes in pulmonary tissue as well as in the blood. Studies have been carried out to detect whether oxidatively modified molecules or cells could be considered possible markers of the disease. We hypothesize here that new insights into COPD could come from enzymes involved in deliberate radical generation (i.e., Nox and NOS family enzymes) as well as from alterations of erythrocyte integrity and function, which could become bioindicators of diagnostic or prognostic value in the near future. C1 [Malorni, Walter] Ist Super Sanita, Dept Drug Res & Evaluat, Sect Cell Aging & Degenerat, I-00161 Rome, Italy. [Minetti, Maurizio] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Leto, Thomas L.] NIAID, Host Def Lab, NIH, Rockville, MD USA. RP Malorni, W (reprint author), Ist Super Sanita, Dept Drug Res & Evaluat, Sect Cell Aging & Degenerat, Viale Regina Elena 299, I-00161 Rome, Italy. EM malorni@iss.it RI Malorni, Walter/G-5874-2016; OI malorni, walter/0000-0002-1223-7000 NR 69 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD APR PY 2008 VL 10 IS 4 BP 829 EP 836 DI 10.1089/ars.2007.1864 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 262VM UT WOS:000253176100015 PM 18179360 ER PT J AU Bray, M AF Bray, Mike TI Highly pathogenic RNA viral infections: Challenges for antiviral research SO ANTIVIRAL RESEARCH LA English DT Review DE viral hemorrhagic fever; viral encephalitis; arbovirus; influenza; H5N1 influenza; filovirus; flavivirus; yellow fever; lassa fever; lassa virus; Ebola hemorrhagic fever; Marburg hemorrhagic fever; Junin virus; argentine hemorrhagic fever; hantavirus; hantavirus pulmonary syndrome; crimean-congo hemorrhagic fever; arenavirus; bunyavirus; alphavirus; Japanese encephalitis; zoonosis; antiviral therapy; antiviral drug; emerging infectious diseases; livestock diseases; foot-and-mouth disease; biodefense ID EBOLA HEMORRHAGIC-FEVER; RIBAVIRIN; VIRUS; TRIAL AB A number of RNA viruses can cause severe disease when transmitted to humans from an animal reservoir. One of them, the recently emerged H5N1 subtype of influenza A virus, has caused several hundred cases of severe disease when transferred directly from domestic poultry. This or another avian subtype could potentially evolve to a form more transmissible by the respiratory route or reassort with a circulating strain to initiate a pandemic. Other zoonotic RNA viruses cause sporadic single cases or outbreaks of hemorrhagic fever or encephalitis that spread inefficiently from person-to-person, and thus remain confined to the geographic range of the maintenance host. RNA viral infections of farm animals, such as foot and mouth disease and classical swine fever, also pose a major threat to human well-being through economic loss and impaired nutrition. Only a few licensed antiviral drugs are available to prevent or treat these conditions. Medications that inhibit the replication of influenza virus might be used in an epidemic both to treat severe disease and to block the spread of infection. The guanosine analog ribavirin has been used to treat a few types of hemorrhagic fever, but there is no specific therapy for the others, or for any type of RNA viral encephalitis. The quest for new antivirals is being supported by government programs and new collaborative research networks. Major efforts will be required to identify active compounds, test their efficacy in laboratory animals, obtain approval for human use and develop rapid diagnostic methods that can identify patients early enough in the disease course for treatment to be of benefit. (C) 2008 Published by Elsevier B.V. C1 NIH, Integrated Res Facil, Div Clin Res, NIAID, Bethesda, MD 20892 USA. RP Bray, M (reprint author), NIH, Integrated Res Facil, Div Clin Res, NIAID, Room 5128,6700A Rockledge Dr, Bethesda, MD 20892 USA. EM mbray@niaid.nih.gov NR 35 TC 27 Z9 29 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2008 VL 78 IS 1 BP 1 EP 8 DI 10.1016/j.antiviral.2007.12.007 PG 8 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 290ZY UT WOS:000255163300001 PM 18243346 ER PT J AU Greenstone, H Spinelli, B Tseng, C Peacock, S Taylor, K Laughlin, C AF Greenstone, Heather Spinelli, Beth Tseng, Christopher Peacock, Susan Taylor, Katherine Laughlin, Catherine TI NIAID resources for developing new therapies for severe viral infections SO ANTIVIRAL RESEARCH LA English DT Article DE adenoviruses; anti-inflammatory; antiviral testing program; avian H5N1; BEIR; biodefense and emerging infections repository; BK virus; BLA; BSL-4 containment; cationic lipid-DNA complexes (CLDC); chemical synthesis; clinical evaluations; cloned genes; cowpox virus; cytomegalovirus; dengue; determination of exceptional circumstances (DEC); Epstein-Barr virus; filoviruses; formulation; hamster-scrapie; hepatitis B virus; hepatitis C virus; herpes simplex type 1 and type 2; highly pathogenic RNA viruses; HIV; human herpes virus 6; human herpes virus 8; immunomodulatory; in vivo testing submission form; IND; influenza type A; intellectual property option (IP option); intellectual property; Junin; juvaris BioTherapeutics; lassa fever; manufacturing; measles; medicinal chemistry; monoclonal antibodies; NDA; NIAID category A; B and C; NIAID; nucleic acids; orthopoxviruses; papillomaviruses; parainfluenza; patent protection; pharmacodynamic; pharmacokinetic; phase I clinical trials; Pichinde; radiolabeled compounds; recombinant proteins; respiratory syncytial virus; Rhinoviruses; rift valley fever; screening agreement; services for the preclinical development of therapeutic agents; severe acute respiratory syndrome (SARS)-associated; coronavirus; synthesis/resynthesis; synthetic peptides; Tacaribe; vaccinia virus; varicella-zoster virus; venezuelan equine encephalitis; west nile; western equine encephalitis viruses; yellow fever ID WEST-NILE-VIRUS; LETHAL MOUSEPOX MODEL; ETHER LIPID ESTERS; IN-VIVO ACTIVITIES; CYTOMEGALOVIRUS-INFECTION; HAMSTER MODEL; COTTON RATS; ORTHOPOXVIRUS INFECTIONS; N-METHANOCARBATHYMIDINE; VACCINIA VIRUS AB Severe viral infections, including hemorrhagic fever and encephalitis, occur throughout the world, but are most prevalent in developing areas that are most vulnerable to infectious diseases. Some of these can also infect related species as illustrated by the threatened extinction of gorillas by Ebola infection in west and central Africa. There are no safe and effective treatments available for these serious infections. In addition to the logistical difficulties inherent in developing a drug for infections that are sporadic and occur mainly in the third world, there is the overwhelming barrier of no hope for return on investment to encourage the pharmaceutical industry to address these unmet medical needs. Therefore, the National Institute of Allergy and infectious Disease (NIAID) has developed and supported a variety of programs and resources to provide assistance and lower the barrier for those who undertake these difficult challenges. The primary programs relevant to the development of therapies for severe viral infections are described and three case studies illustrate how they have been used. In addition, contact information for accessing these resources is supplied. Published by Elsevier B.V. C1 [Greenstone, Heather; Spinelli, Beth; Tseng, Christopher; Peacock, Susan; Taylor, Katherine; Laughlin, Catherine] NIAID, NIH, Div Microbial & Infect Dis, Bethesda, MD 20892 USA. RP Laughlin, C (reprint author), NIAID, NIH, Div Microbial & Infect Dis, Bethesda, MD 20892 USA. EM claughlin@niaid.nih.gov NR 63 TC 5 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2008 VL 78 IS 1 BP 51 EP 59 DI 10.1016/j.antiviral.2007.10.006 PG 9 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 290ZY UT WOS:000255163300006 PM 18061283 ER PT J AU Higgs, ES Hayden, FG Chotpitayasunondh, T Whitworth, J Farrar, J AF Higgs, Elizabeth S. Hayden, Frederick G. Chotpitayasunondh, Tawee Whitworth, Jimmy Farrar, Jeremy TI The Southeast Asian Influenza Clinical Research Network: Development and challenges for a new multilateral research endeavor SO ANTIVIRAL RESEARCH LA English DT Article DE developing networks; emerging infectious diseases; clinical research; pandemic preparedness; avian influenza; H5N1 influenza; Southeast Asia AB The Southeast Asia Influenza Clinical Research Network (SEA ICRN) (www.seaclinicalresearch.org) is a recently developed multilateral, collaborative partnership that aims to advance scientific knowledge and management of human influenza through integrated clinical investigation. The partnership of hospitals and institutions in Indonesia, Thailand, United Kingdom, United States, and Viet Nam was established in late 2005 after agreement on the general principles and mission of the initiative and after securing initial financial support. The establishment of the SEA ICRN was both a response to the re-emergence of the highly pathogenic avian influenza A(H5N1) virus in Southeast Asia in late 2003 and an acknowledgment that clinical trials on emerging infectious diseases require prepared and coordinated research capacity. The objectives of the Network also include building sustainable research capacity in the region, compliance with international standards, and prompt dissemination of information and sharing of samples. The scope of research includes diagnosis, pathogenesis, treatment and prevention of human influenza due to seasonal or novel viruses. The Network has overcome numerous logistical and scientific challenges but has now successfully initiated several clinical trials. The establishment of a clinical research network is a vital part of preparedness and an important element during an initial response phase to a pandemic. (C) 2007 Elsevier B.V. All rights reserved. C1 [Higgs, Elizabeth S.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Hayden, Frederick G.] WHO, Global Influenza Programme, CH-1211 Geneva, Switzerland. [Chotpitayasunondh, Tawee] Minist Publ Hlth, Dept Med Serv, Queen Sirikit Natl Inst Child Hlth, Bangkok, Thailand. [Whitworth, Jimmy] Wellcome Trust Res Labs, London, England. [Farrar, Jeremy] Hosp Trop Dis, Ho Chi Minh City, Vietnam. [Farrar, Jeremy] Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam. RP Higgs, ES (reprint author), NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. EM ehiggs@niaid.nih.gov OI Farrar, Jeremy/0000-0002-2700-623X NR 3 TC 16 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2008 VL 78 IS 1 BP 64 EP 68 DI 10.1016/j.antiviral.2007.10.008 PG 5 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 290ZY UT WOS:000255163300008 PM 18295355 ER PT J AU Beigel, J Bray, M AF Beigel, John Bray, Mike TI Current and future antiviral therapy of severe seasonal and avian influenza SO ANTIVIRAL RESEARCH LA English DT Review DE influenza; influenza virus; avian influenza; H5N1 influenza virus; adamantane; neuraminidase; peramivir; oseltamivir; zanamivir; antiviral therapy ID A H5N1 VIRUS; LOWER RESPIRATORY-TRACT; RANDOMIZED CONTROLLED-TRIAL; IN-VIVO ACTIVITIES; NEURAMINIDASE INHIBITOR; HUMAN INFECTION; CYTOKINE RESPONSES; HUMAN AIRWAY; HONG-KONG; OSELTAMIVIR RESISTANCE AB The currently circulating H3N2 and H1N1 subtypes of influenza A virus cause a transient, febrile upper respiratory illness in most adults and children ("seasonal influenza"), but infants, the elderly, immunodeficient and chronically ill persons may develop life-threatening primary viral pneumonia or complications such as bacterial pneumonia. By contrast, avian influenza viruses such as the H5N1 virus that recently emerged in Southeast Asia can cause severe disease when transferred from domestic poultry to previously healthy people ("avian influenza"). Most H5N1 patients present with fever, cough and shortness of breath that progress rapidly to adult respiratory distress syndrome. In seasonal influenza, viral replication remains confined to the respiratory tract, but limited studies indicate that H5N1 infections are characterized by systemic viral dissemination, high cytokine levels and multiorgan failure. Gastrointestinal infection and encephalitis also occur. The licensed anti-influenza drugs (the M2 ion channel blockers, amantadine and rimantadine, and the neuraminidase inhibitors, oseltamivir and zanamivir) are beneficial for uncomplicated seasonal influenza, but appropriate dosing regimens for severe seasonal or H5N1 viral infections have not been defined. Treatment options may be limited by the rapid emergence of drug-resistant viruses. Ribavirin has also been used to a limited extent to treat influenza. This article reviews licensed drugs and treatments under development, including high-dose oseltamivir; parenterally administered neuraminiclase inhibitors, peramivir and zanamivir; dimeric forms of zanamivir; the RNA polymerase inhibitor T-705; a ribavirin prodrug, viramidine; polyvalent and monoclonal antibodies; and combination therapies. Published by Elsevier B.V. C1 [Beigel, John; Bray, Mike] NIAID, NIH, Bethesda, MD 20892 USA. RP Beigel, J (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM jbeigel@niaid.nih.gov RI Beigel, John/A-7111-2009 FU Intramural NIH HHS [Z99 AI999999] NR 131 TC 139 Z9 159 U1 4 U2 41 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2008 VL 78 IS 1 BP 91 EP 102 DI 10.1016/j.antiviral.2008.01.003 PG 12 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 290ZY UT WOS:000255163300011 PM 18328578 ER PT J AU Donelson, E Chen, LP Zhang, XL Goswami, P Song, BJ Hardwick, JP AF Donelson, Ellen Chen, Liping Zhang, Xiaolan Goswami, Puja Song, Byoung J. Hardwick, James P. TI Genomic structure and regulation of the rat hepatic CYP4F1 gene by peroxisome proliferators SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE cytochrome P450; CYP4F1 gene; peroxisome proliferators; PPAR alpha; HNF4 alpha; gene regulation; microsome; lipids ID HEPATOCYTE NUCLEAR FACTOR-4-ALPHA; APOLIPOPROTEIN C-III; ACTIVATED RECEPTOR; TRANSCRIPTIONAL SUPPRESSION; MOLECULAR-MECHANISMS; OMEGA-HYDROXYLASES; RETINOIC ACID; MESSENGER-RNA; LIVER-INJURY; EXPRESSION AB The rat hepatic gene CYP4F1 encodes a fatty acid omega hydroxylase P450 that metabolizes proinflammatory eicosanoids and long-chain fatty acids. We have completely sequenced the CYP4F1 gene (Accession Nos. AF200361 and AF181083), identified multiple transcription start sites, and characterized a strong core promoter region, -760/116, induced by retinoic acids and peroxisome proliferators in rat hepatoma McA-RH7777 cells. Three peroxisome proliferator responsive elements (PPRE) bind both PPAR alpha/RXR alpha and HNF4 alpha. Co-transfection of McA-RH7777 cells with the -760/116 reporter construct and PPAR alpha/RXR alpha or HNF4 alpha showed that HNF4 alpha activated while PPAR alpha/RXR alpha inhibited CYP4F1 promoter activity. Treating cells with Wy14,643 reversed all initial effects, indicating co-regulation of CYP4F1 gene transcription by PPAR alpha/RXR alpha and HNF4 alpha. Chromatin immunoprecipitation analysis of cells treated with Wy14,643 showed association of PPAR alpha/RXR alpha with the active transcription of the CYP4F1 gene while in clofibrate treated rats HNF4 alpha binds during gene repression, suggesting differential regulation of the CYP4F1 gene in vivo and in cell lines. Published by Elsevier Inc. C1 [Donelson, Ellen; Zhang, Xiaolan; Hardwick, James P.] Northeastern Ohio Univ Coll Med & Pharm, Dept Biochem & Mol Pathol, Rootstown, OH 44272 USA. [Chen, Liping; Goswami, Puja] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Endocrinol Diabetes & Hypertens, Boston, MA 02115 USA. [Song, Byoung J.] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. RP Hardwick, JP (reprint author), Northeastern Ohio Univ Coll Med & Pharm, Dept Biochem & Mol Pathol, 4209 State Route 44,POB 95, Rootstown, OH 44272 USA. EM jph@neoucom.edu NR 50 TC 3 Z9 3 U1 0 U2 0 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 APR 1 PY 2008 VL 472 IS 1 BP 1 EP 16 DI 10.1016/j.abb.2008.01.018 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 282BY UT WOS:000254543800001 PM 18262487 ER PT J AU Yamaguchi, Y Beer, JZ Hearing, VJ AF Yamaguchi, Yuji Beer, Janusz Z. Hearing, Vincent J. TI Melanin mediated apoptosis of epidermal cells damaged by ultraviolet radiation: factors influencing the incidence of skin cancer SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE apoptosis; UV; photocarcinogenesis; melanin; DNA repair ID MELANOCORTIN-1 RECEPTOR; DNA-REPAIR; DISTRIBUTION PATTERNS; UV-RADIATION; IN-VITRO; PIGMENTATION; EXPOSURE; PHOTOPROTECTION; KERATINOCYTES; MELANOSOMES AB Ultraviolet (UV)-induced skin cancers, including melanomas and basal/squamous cell carcinomas, occur more frequently in individuals with fair skin than in those with dark skin. Melanin plays an important role in protecting the skin against UV radiation and levels of melanin correlate inversely with amounts of DNA damage induced by UV in human skin of different racial/ethnic groups. The objectives of this study are to review recent progress in our understanding of mechanisms underlying differences in cancer incidence in skins of different colors, particularly between Black and White skin. More specifically, we review DNA damage and apoptosis in various types of skin before and after exposure to UV in our human study protocols using a single UV dose, either one minimal erythema dose (MED) or a similar low dose of 180 - 200 J/m(2). Our data and other published reports indicate that several major mechanisms underlie the increased rates of photocarcinogenesis in fair/light skin. First, UV-induced DNA damage in the lower epidermis (including keratinocyte stem cells and melanocytes) is more effectively prevented in darker skin. Second, rates of repair of DNA damage can differ significantly in individuals. Third, UV-induced apoptosis to remove potentially precancerous cells is significantly greater in darker skin. These results suggest that pigmented epidermis is an efficient UV filter and that UV damaged cells are removed more efficiently in darker skin. The combination of decreased DNA damage and more efficient removal of UV-damaged cells may play a critical role in the decreased photocarcinogenesis seen in individuals with darker skin. C1 [Yamaguchi, Yuji] Osaka Univ, Grad Sch Med, Dept Dermatol, Suita, Osaka, Japan. [Yamaguchi, Yuji; Hearing, Vincent J.] Natl Inst Hlth, Pigment Cell Res Sect, Cell Biol Lab, Natl Canc Inst, Bethesda, MD USA. [Yamaguchi, Yuji] Nagoya City Univ, Grad Sch Med, Dept Geriatr & Environm Dermatol, Nagoya, Aichi, Japan. [Beer, Janusz Z.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Yamaguchi, Y (reprint author), Osaka Univ, Grad Sch Med, Dept Dermatol, Suita, Osaka, Japan. EM yujin@med.nagoya-cu.acjp RI Yamaguchi, Yuji/B-9312-2008 NR 44 TC 16 Z9 21 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD APR PY 2008 VL 300 SU 1 BP S43 EP S50 DI 10.1007/s00403-007-0807-0 PG 8 WC Dermatology SC Dermatology GA 293WH UT WOS:000255365600006 PM 17985102 ER PT J AU Rohde, P Silva, SG Tonev, ST Kennard, BD Vitiello, B Kratochvil, CJ Reinecke, MA Curry, JF Simons, AD March, JS AF Rohde, Paul Silva, Susan G. Tonev, Simon T. Kennard, Betsy D. Vitiello, Benedetto Kratochvil, Christopher J. Reinecke, Mark A. Curry, John F. Simons, Anne D. March, John S. TI Achievement and maintenance of sustained response during the treatment for adolescents with depression study continuation and maintenance therapy SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; ASTERISK-D REPORT; FOLLOW-UP; PHARMACOTHERAPY; DISORDER; CHILDREN; RELAPSE; RECURRENCE; PSYCHOTHERAPY; TADS AB Context: The Treatment for Adolescents With Depression Study evaluated fluoxetine (FLX), cognitive behavioral therapy (CBT), and FLX/CBT combination (COMB) vs pill placebo in 439 adolescents with major depressive disorder. Treatment consisted of 3 stages: (1) acute (12 weeks), (2) continuation (6 weeks), and (3) maintenance (18 weeks). . Objective: To examine rates of achieving and maintaining sustained response during continuation and maintenance treatments. Design: Randomized controlled trial. Response was determined by blinded independent evaluators. Setting: Thirteen US sites. Patients: Two hundred forty-two FLX, CBT, and COMB patients in their assigned treatment at the end of stage 1. Interventions: Stage 2 treatment varied based on stage 1 response. Stage 3 consisted of 3 CBT and/or pharmacotherapy sessions and, if applicable, continued medication. Main Outcome Measures: Sustained response was defined as 2 consecutive Clinical Global Impression-Improvement ratings of 1 or 2 ("full response"). Patientsachieving sustained response were classified on subsequent nonresponse status. Results: Among 95 patients (39.3%) who had not achieved sustained response by week 12 (29.1% COMB, 32.5% FLX, and 57.9% CBT), sustained response rates during stages 2 and 3 were 80.0% COMB, 61.5% FLX, and 77.3% CBT (difference not significant). Among the remaining 147 patients (60.7%) who achieved sustained response by week 12, CBT patients were more likely than FLX patients to maintain sustained response through week 36 (96.9% vs; 74.1%; P =.007; 88.5% of COMB patients maintained sustained response through week 36). Total rates of sustained response by week 36 were 88.4% COMB, 82.5% FLX, and 75.0% CBT. Conclusions: Most adolescents with depression who had not achieved sustained response during acute treatment did achieve that level of improvement during continuation and maintenance therapies. The possibility that CBT may help the subset of adolescents with depression who achieve early sustained response maintain their response warrants further investigation. C1 [Rohde, Paul] Oregon Res Inst, Eugene, OR 97403 USA. [Simons, Anne D.] Univ Oregon, Eugene, OR 97403 USA. [Curry, John F.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Silva, Susan G.; Tonev, Simon T.; March, John S.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Kennard, Betsy D.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. [Kratochvil, Christopher J.] Univ Nebraska Med Ctr, Omaha, NE USA. [Reinecke, Mark A.] Northwestern Univ, Evanston, IL USA. RP Rohde, P (reprint author), Oregon Res Inst, 1715 Franklin Blvd, Eugene, OR 97403 USA. EM paulr@ori.org FU DS NIH HHS [NIMH 98-DS-0008]; NIMH NIH HHS [N01 MH080008] NR 34 TC 20 Z9 22 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2008 VL 65 IS 4 BP 447 EP 455 DI 10.1001/archpsyc.65.4.447 PG 9 WC Psychiatry SC Psychiatry GA 285BJ UT WOS:000254752000009 PM 18391133 ER PT J AU Wang, RX Han, GC Wang, JN Song, L Chen, GJ Xu, RN Zhang, CM Yu, M Qian, JH Shen, BF Li, Y AF Wang, Renxi Han, Gencheng Wang, Jianan Song, Lun Chen, Guojiang Xu, Ruonan Zhang, Chunmei Yu, Ming Qian, Jiahua Shen, Beifen Li, Yan TI GAD-IgG-inducing CD4(+)Foxp3(+)Treg cells suppressing diabetes are involved in the increasing ratio of CD80(+): CD86(+) cells in NOD mice SO ARCHIVES OF MEDICAL RESEARCH LA English DT Article DE CD4(+)Foxp3(+)Treg cells; CD80; CD86; diabetes; Foxp3; NOD mice ID REGULATORY T-CELLS; TOLERANCE; B7; MECHANISMS; INDUCTION; FOXP3 AB Background. Our previous studies have demonstrated that GAD-IgG-transduced splenocytes protect non-obese diabetic (NOD) mice from diabetes by in vitro-inducing CD4(+)Foxp3(+)Treg cells. However, the underlying mechanisms by which CD4(+)Foxp3(+)Treg cells suppress diabetes remain unclear. Methods. Seven-week-old female NOD mice were intravenously injected with GAD-IgG-transduced splenocytes. The ratio of CD80(+):CD86(+) cells in splenocytes was analyzed by flow cytometry. The effect of the ratio of CD80(+):CD86(+) cells on tolerance, diabetes prevention, and Foxp3 expression in GAD-IgG-treated NOD mice was tested by in vitro proliferation, in vivo antibody block, and semi-quantified RT-PCR, respectively. Results. We found that the ratio of CD80(+):CD86(+) cells increased in GAD-IgG-treated NOD mice. After CD4(+)Treg cells were depleted from GAD-IgG-transduced splenocytes before transfer, the ratio of CD80(+):CD86(+) cells decreased in NOD mice recipients. The increasing ratio of CD80(+):CD86(+) cells was positively associated with tolerance, diabetes prevention, and the high level of Foxp3 in GAD-IgG-treated NOD mice. Conclusions. These findings suggest that the high ratio of CD80(+):CD86(+) cells is required for the suppressive function of GAD-IgG-inducing CD4(+)Foxp3(+)Treg cells in NOD mice. (c) 2008 IMSS. Published by Elsevier Inc. C1 [Wang, Renxi; Han, Gencheng; Wang, Jianan; Song, Lun; Chen, Guojiang; Xu, Ruonan; Zhang, Chunmei; Yu, Ming; Shen, Beifen; Li, Yan] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China. [Zhang, Chunmei] Henan Univ, Cellular & Mol Immunol Lab, Kaifeng, Peoples R China. [Qian, Jiahua] Natl Canc Inst, Vaccine Branch, Bethesda, MD USA. RP Li, Y (reprint author), Chinese Acad Med Sci, Inst Basic Med Sci, Dept Mol Immunol, Taiping Rd 27, Beijing 100850, Peoples R China. EM liyan62033@yahoo.com.cn NR 17 TC 1 Z9 3 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0188-4409 J9 ARCH MED RES JI Arch. Med. Res. PD APR PY 2008 VL 39 IS 3 BP 299 EP 305 DI 10.1016/j.aremed.2007.11.007 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 268CL UT WOS:000253555400005 PM 18279702 ER PT J AU Rohrer, JD Warren, JD Omar, R Mead, S Beck, J Revesz, T Holton, J Stevens, JM Al-Sarraj, S Pickering-Brown, SM Hardy, J Fox, NC Collinge, J Warrington, EK Rossor, MN AF Rohrer, Jonathan D. Warren, Jason D. Omar, Rohani Mead, Simon Beck, Jonathan Revesz, Tamas Holton, Janice Stevens, John M. Al-Sarraj, Safa Pickering-Brown, Stuart M. Hardy, John Fox, Nick C. Collinge, John Warrington, Elizabeth K. Rossor, Martin N. TI Parietal lobe deficits in frontotemporal lobar degeneration caused by a mutation in the progranulin gene SO ARCHIVES OF NEUROLOGY LA English DT Article ID UBIQUITIN-POSITIVE INCLUSIONS; CORTICOBASAL DEGENERATION; CLINICAL-FEATURES; DEMENTIA; CHROMOSOME-17; APHASIA; CONSENSUS; CRITERIA; OVERLAP; LESIONS AB Objective: To describe the clinical, neuropsychologic, and radiologic features of a family with a C31LfsX35 mutation in the progranulin gene (PGRN) (GenBank CCDS11483.1). Design: Case series. Patients: A large British kindred (DRC255) with a PGRN mutation was assessed. Affected individuals presented with a mean age of 57.8 years (range, 54-67 years) and a mean disease duration of 6.1 years (range, 2-11 years). Results: All patients exhibited a clinical and radiologic phenotype compatible with frontotemporal lobar degeneration based on current consensus criteria. However, unlike sporadic frontotemporal lobar degeneration, parietal deficits, consisting of dyscalculia, visuoperceptual/visuospatial dysfunction, and/or limb apraxia, were a common feature, and brain imaging showed posterior extension of frontotemporal atrophy to involve the parietal lobes. Other common clinical features included language output impairment with either dynamic aphasia or nonfluent aphasia and a behavioral syndrome dominated by apathy. Conclusion: We suggest that parietal deficits may be a prominent feature of PGRN mutations and that these deficits may be caused by disruption of frontoparietal functional pathways. C1 [Rohrer, Jonathan D.; Warren, Jason D.; Omar, Rohani; Fox, Nick C.; Warrington, Elizabeth K.; Rossor, Martin N.] UCL, Inst Neurol, Dementia Res Ctr, London WC1N 3BG, England. [Mead, Simon; Beck, Jonathan; Collinge, John] UCL, Inst Neurol, Med Res Council Prion Unit, Dept Neurodegenerat Dis, London WC1N 3BG, England. [Revesz, Tamas; Holton, Janice] UCL, Inst Neurol, Dept Mol Sci, London WC1N 3BG, England. [Stevens, John M.] Natl Hosp Neurol & Neurosurg, Dept Clin Neuroradiol, London WC1N 3BG, England. [Al-Sarraj, Safa] Kings Coll London, Dept Clin Neuropathol, London WC2R 2LS, England. [Pickering-Brown, Stuart M.] Univ Manchester, Div Regenerat Med, Dept Med, Manchester, Lancs, England. [Hardy, John] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Rossor, MN (reprint author), UCL, Inst Neurol, Dementia Res Ctr, Queen Sq, London WC1N 3BG, England. EM m.rossor@dementia.ion.ucl.ac.uk RI Pickering-Brown, Stuart/D-4008-2009; Mead, Simon/E-9414-2011; Holton, Janice/F-6831-2011; Hardy, John/C-2451-2009; Fox, Nick/B-1319-2009; Revesz, Tamas/A-8732-2010 OI Pickering-Brown, Stuart/0000-0003-1561-6054; Mead, Simon/0000-0002-4326-1468; Holton, Janice/0000-0002-3882-5249; Fox, Nick/0000-0002-6660-657X; Revesz, Tamas/0000-0003-2501-0259 FU Medical Research Council [, G0400356, G0401247, G0600676, G0600984, G0601846, G0701075, MC_U123160651, MC_U123192748]; Wellcome Trust [077133, ] NR 41 TC 31 Z9 33 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2008 VL 65 IS 4 BP 506 EP 513 DI 10.1001/archneur.65.4.506 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 286GZ UT WOS:000254835700011 PM 18413474 ER PT J AU Bakowska, JC Wang, H Xin, B Sumner, CJ Blackstone, C AF Bakowska, Joanna C. Wang, Heng Xin, Baozhong Sumner, Charlotte J. Blackstone, Craig TI Lack of spartin protein in Troyer syndrome - A loss-of-function disease mechanism? SO ARCHIVES OF NEUROLOGY LA English DT Article ID HEREDITARY SPASTIC PARAPLEGIA; SPG20 AB Background: Hereditary spastic paraplegias (SPG1-SPG33) are characterized by progressive spastic weakness of the lower limbs. A nucleotide deletion (1110delA) in the (SPG20; OMIM 275900) spartin gene is the origin of autosomal recessive Troyer syndrome. This mutation is predicted to cause premature termination of the spartin protein. However, it remains unknown whether this truncated spartin protein is absent or is present and partially functional in patients. Objective: To determine whether the truncated spartin protein is present or absent in cells derived from patients with Troyer syndrome. Design: Case report. Setting: Academic research. Patients: We describe a new family with Troyer syndrome due to the 1110delA mutation. Main Outcome Measures: We cultured primary fibroblasts and generated lymphoblasts from affected individuals, carriers, and control subjects and subjected these cells to immunoblot analyses. Results: Spartin protein is undetectable in several cell lines derived from patients with Troyer syndrome. Conclusions: Our data suggest that Troyer syndrome results from complete loss of spartin protein rather than from the predicted partly functional fragment. This may reflect increased protein degradation or impaired translation. C1 [Bakowska, Joanna C.; Blackstone, Craig] NINDS, Cellular Neurol Unit, NIH, Bethesda, MD 20892 USA. [Sumner, Charlotte J.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Wang, Heng; Xin, Baozhong] DDC Clin Special Needs Children, Middlefield, OH USA. RP Blackstone, C (reprint author), NINDS, Cellular Neurol Unit, NIH, Bldg 35,Room 2C 913,9000 Rockville Pike, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov FU Intramural NIH HHS NR 16 TC 24 Z9 24 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2008 VL 65 IS 4 BP 520 EP 524 DI 10.1001/archneur.65.4.520 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 286GZ UT WOS:000254835700013 PM 18413476 ER PT J AU Isenberg, JS Roberts, DD Frazier, WA AF Isenberg, Jeff S. Roberts, David D. Frazier, William A. TI Cd47: A new target in cardiovascular therapy SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE thrombospondin-1; CD47; nitric oxide; ischemia; platelet aggregation ID INTEGRIN-ASSOCIATED PROTEIN; CELL-BINDING DOMAIN; SIGNAL-REGULATORY PROTEIN; ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; C-TERMINAL PEPTIDE; NITRIC-OXIDE; PLATELET-AGGREGATION; HUMAN THROMBOSPONDIN; METABOLIC SYNDROME AB CD47, originally named integrin-associated protein, is a receptor for thrombospondin-1. A number of important roles for CD47 have been defined in regulating the migration, proliferation, and survival of vascular cells, and in regulation of innate and adaptive immunity. The recent discovery that thrombospondin-1 acts via CD47 to inhibit nitric oxide signaling throughout the vascular system has given new importance and perhaps a unifying mechanism of action to these enigmatic proteins. Here we trace the development of this exciting new paradigm for CD47 function in vascular physiology. C1 [Frazier, William A.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. [Isenberg, Jeff S.; Roberts, David D.] Natl Canc Inst, Natl Inst Hlth, Pathol Lab, Bethesda, MD USA. RP Frazier, WA (reprint author), Washington Univ, Sch Med, Dept Biochem & Mol Biophys, 660 S Euclid Ave, St Louis, MO 63110 USA. EM frazier@wustl.edu RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS; NHLBI NIH HHS [HL54390, R56 HL054390, R01 HL054390-09A2, R01 HL054390]; NIGMS NIH HHS [R01 GM057573-08, R01 GM057573, GM57573] NR 95 TC 24 Z9 25 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2008 VL 28 IS 4 BP 615 EP 621 DI 10.1161/ATVBAHA.107.158154 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 276YK UT WOS:000254179400006 PM 18187671 ER PT J AU Blair-Levy, JM Watts, CE Fiorientino, NM Dimitriadis, EK Marini, JC Lipsky, PE AF Blair-Levy, J. M. Watts, C. E. Fiorientino, N. M. Dimitriadis, E. K. Marini, J. C. Lipsky, P. E. TI A type I collagen defect leads to rapidly progressive osteoarthritis in a mouse model SO ARTHRITIS AND RHEUMATISM LA English DT Article ID BONE-MINERAL DENSITY; RADIOGRAPHIC KNEE OSTEOARTHRITIS; SUBCHONDRAL BONE; ARTICULAR-CARTILAGE; OSTEOGENESIS IMPERFECTA; HIP OSTEOARTHRITIS; MURINE MODEL; RISK-FACTORS; OSTEOPOROSIS; DAMAGE AB Objective. This study was undertaken to test the hypothesis that abnormalities of the subchondral bone can result in osteoarthritis (OA). Methods. We used a knockin model of human osteogenesis imperfecta, the Brittle IV (Brtl) mouse, in which defective type I collagen is expressed in bone. OA in individual mice was documented by micro-magnetic resonance imaging (micro-MRI) and micro-computed tomography (micro-CT). Alterations in the knee joints were confirmed by histopathologic and immunohistochemical analysis. In addition, atomic force microscopy (AFM) was used to assess the ultrastructure of the articular cartilage and subchondral bone matrix. Results. Brtl mice had decreased integrity of bone but initially normal articular cartilage. However, by the second month of life, Brtl mice developed alterations of the cartilage that were characteristic of OA, as documented by micro-CT, micro-MRI, and histologic evaluation. In addition, chondrocyte loss and breakdown of the collagen matrix in the residual cartilage were demonstrated using AFM. Conclusion. The Brtl mouse model demonstrates that progressive destruction of articular cartilage characteristic of OA may be secondary to altered architecture of the underlying subchondral bone. C1 [Blair-Levy, J. M.; Watts, C. E.; Fiorientino, N. M.; Dimitriadis, E. K.; Lipsky, P. E.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Marini, J. C.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, NIH, Bldg 10, 6D47C,900 Rocksville Pike, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov FU Intramural NIH HHS NR 48 TC 31 Z9 32 U1 2 U2 15 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 2008 VL 58 IS 4 BP 1096 EP 1106 DI 10.1002/art.23277 PG 11 WC Rheumatology SC Rheumatology GA 293OS UT WOS:000255345200022 PM 18383364 ER PT J AU Cao, JJ Biggs, ML Barzilay, J Konen, J Psaty, BM Kuller, L Bleyer, AJ Olson, J Wexler, J Summerson, J Cushman, M AF Cao, Jie J. Biggs, Mary L. Barzilay, Joshua Konen, Joseph Psaty, Bruce M. Kuller, Lewis Bleyer, Anthony J. Olson, Jean Wexler, Jason Summerson, John Cushman, Mary TI Cardiovascular and mortality risk prediction and stratification using urinary albumin excretion in older adults ages 68-102: The cardiovascular Health Study SO ATHEROSCLEROSIS LA English DT Article DE microalbuminuria; macroalbuminuria; cardiovascular disease; mortality ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; MICROALBUMINURIA; POPULATION; EVENTS; PREVALENCE; MARKERS; DEATH AB Background: Elevated urinary albumin excretion (UAE) is associated with the risk of cardiovascular disease (CVD) and all-cause mortality. We tested the hypothesis that elevated UAE improves cardiovascular risk stratification in an elderly cohort aged 68-102 years. Methods: We evaluated UAE in 3112 participants of the Cardiovascular Health Study who attended the 1996-1997 examination and had median follow up of 5.4 years. Elevated UAE was defined as urinary albumin to creatinine ratio >= 30 mu g/mg. Microalbuminuria and macroalbuminuria were defined as urinary albumin to creatinine ratio 30-300 mu g/mg and > 300 mu g/mg, respectively. Outcomes included CVD (myocardial infarction, stroke, cardiovascular death) and all-cause mortality. Cox proportional hazards models were used to assess the risk of outcomes associated with elevated UAE. Results: The prevalence of elevated UAE was 14.3%, 17.1% and 26.9% in those aged 68-74, 75-84 and 85-102 years, respectively. CVD incidence and all-cause mortality were doubled (7.2% and 8.1% per year) in those with microalbuminuria and tripled (11.1% and 12.3% per year) in those with macroalbuminuria compared to those with normal UAE (3.3% and 3.8% per year). The increased CVD and mortality risks were observed in all age groups after adjustment for conventional risk factors. The adjusted population attributable risk percent of CVD and all-cause mortality for elevated UAE was 11 % and 12%, respectively. When participants were cross-classified by UAE and Framingham Risk Score categories, the 5-year cumulative incidence of coronary heart disease among participants with elevated UAE and a 5-year predicted risk of 5-10% was 20%, substantially higher than 6.3% in those with IJAE < 30 mu g/mg. Conclusion: Elevated UAE was associated with an increased risk of CVD and all-cause mortality in all age groups from 68 to 102 years. Combining elevated UAE with the Framingham risk scores may improve risk stratification for CVD in the elderly. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Cao, Jie J.] SUNY Stony Brook, Div Cardiol, Res Dept, St Francis Hosp, Roslyn, NY 11576 USA. [Biggs, Mary L.; Psaty, Bruce M.] Univ Washington, Seattle, WA 98195 USA. [Barzilay, Joshua] Kaiser Permanente, Atlanta, GA USA. [Konen, Joseph] Pfizer Inc, Ann Arbor, MI USA. [Kuller, Lewis] Univ Pittsburgh, Pittsburgh, PA USA. [Bleyer, Anthony J.; Summerson, John] Wake Forest Univ, Winston Salem, NC 27109 USA. [Olson, Jean] NIH, Bethesda, MD 20892 USA. [Wexler, Jason] Univ Maryland, Baltimore, MD 21201 USA. [Cushman, Mary] Univ Vermont, Burlington, VT USA. RP Cao, JJ (reprint author), SUNY Stony Brook, Div Cardiol, Res Dept, St Francis Hosp, 100 Port Washington Blvd, Roslyn, NY 11576 USA. EM Jane.Cao@chsli.org FU NHLBI NIH HHS [N01-HC-85086, N01 HC-15103, N01-HC-35129, N01-HC-85079] NR 25 TC 27 Z9 27 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2008 VL 197 IS 2 BP 806 EP 813 DI 10.1016/j.atherosclerosis.2007.07.029 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 295DJ UT WOS:000255454900041 PM 17875308 ER PT J AU Shewmaker, F Ross, ED Tycko, R Wickner, RB AF Shewmaker, Frank Ross, Eric D. Tycko, Robert Wickner, Reed B. TI Amyloids of shuffled prion domains that form Prions have a parallel in-register beta-sheet structure SO BIOCHEMISTRY LA English DT Article ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; HET-S PRION; YEAST PRION; SACCHAROMYCES-CEREVISIAE; EXPERIMENTAL CONSTRAINTS; PROTEIN; FIBRILS; PEPTIDE; URE2P AB The [URE3] and [PSI+] prions of Saccharomyces cerevisiae are self-propagating amyloid forms of Ure2p and Sup35p, respectively. The Q/N-rich N-terminal domains of each protein are necessary and sufficient for the prion properties of these proteins, forming in each case their amyloid cores. Surprisingly, shuffling either prion domain, leaving amino acid content unchanged, does not abrogate the ability of the proteins to become prions. The discovery that the amino acid composition of a polypeptide, not the specific sequence order, determines prion capability seems contrary to the standard folding paradigm that amino acid sequence determines protein fold. The shuffleability of a prion domain further suggests that the beta-sheet structure is of the parallel in-register type, and indeed, the normal Ure2 and Sup35 prion domains have such a structure. We demonstrate that two shuffled Ure2 prion domains capable of being prions form parallel in-register beta-sheet structures, and our data indicate the same conclusion for a single shuffled Sup35 prion domain. This result confirms our inference that shuffleability indicates parallel in-register structure. C1 [Shewmaker, Frank; Tycko, Robert; Wickner, Reed B.] NIDDK, NIH, Lab Biochem & Genet, Bethesda, MD 20892 USA. [Ross, Eric D.] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. [Tycko, Robert] NIDDK, NIH, Lab Chem Phys, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDK, NIH, Lab Biochem & Genet, Bldg 8,Room 225, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov; wickner@helix.nih.gov FU Intramural NIH HHS NR 49 TC 51 Z9 51 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 1 PY 2008 VL 47 IS 13 BP 4000 EP 4007 DI 10.1021/bi7024589 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 280EO UT WOS:000254408200004 PM 18324784 ER PT J AU DeMarc, RA George, TC Morrissey, PJ Harmon, I Peterson, EJ Burbach, BJ Shimizu, Y Matsuda, JL Gapin, L Connors, M Dowdell, K Farrar, JD AF DeMarc, R. A. George, T. C. Morrissey, P. J. Harmon, I. Peterson, E. J. Burbach, B. J. Shimizu, Y. Matsuda, J. L. Gapin, L. Connors, M. Dowdell, K. Farrar, J. D. TI Meaurement of nuclear translocation in primary T cells using the ImageStream multispectral imaging flow cytometer SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Meeting Abstract C1 Amnis Corp, Seattle, WA 98121 USA. Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA. Natl Jewish Med & Res Ctr, Integrated Dept Immunol, Denver, CO 80206 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. Univ Texas SW Med Ctr Dallas, Ctr Immunol, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD APR PY 2008 VL 86 IS 2 BP 207 EP 207 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 287YE UT WOS:000254952600061 ER PT J AU Rapoport, SI AF Rapoport, Stanley I. TI Drug efficacy against bipolar disorder correlates with its ability to downregulate the rat brain arachidonic acid cascade SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 2 BP 1S EP 1S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700004 ER PT J AU Di Martino, A Scheres, A Margulies, D Kelly, CAM Uddin, LQ Shehzad, Z Biswal, BB Walters, JR Castellanos, FX Milham, MP AF Di Martino, Adriana Scheres, Anouk Margulies, Daniel Kelly, Clare A. M. Uddin, Lucina Q. Shehzad, Zarrar Biswal, Bharat B. Walters, Judith R. Castellanos, F. Xavier Milham, Michael P. TI Functional connectivity of human striatum: A resting state fMRI study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Di Martino, Adriana; Margulies, Daniel; Kelly, Clare A. M.; Uddin, Lucina Q.; Shehzad, Zarrar; Castellanos, F. Xavier; Milham, Michael P.] NYU, Ctr Child Study, Phyllis Green & Randolph Cowen Inst Pediat Neuros, New York, NY USA. [Scheres, Anouk] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. [Biswal, Bharat B.] Univ Med & Dent New Jersey, Dept Radiol, Newark, NJ 07103 USA. [Walters, Judith R.] Natl Inst Neurol Disorders & Stroke, Neurophysiol Pharmacol Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 6 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 20 BP 7S EP 7S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700022 ER PT J AU Catapano, LA Nanavati, D Chen, G Markey, SR Manji, HK AF Catapano, Lisa A. Nanavati, Dhaval Chen, Guang Markey, Sanford R. Manji, Husseini K. TI Mood stabilizer-induced changes in the postsynaptic density Proteome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Catapano, Lisa A.; Chen, Guang; Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. [Nanavati, Dhaval; Markey, Sanford R.] NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 38 BP 13S EP 13S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700040 ER PT J AU Voon, V Brezing, C Reynolds, B Gallea, C Skaljic, M Potenza, M Dolan, RJ Hallett, M AF Voon, Valerie Brezing, Christina Reynolds, Brady Gallea, Cecile Skaljic, Meliha Potenza, Marc Dolan, Raymond J. Hallett, Mark TI The neural correlates of delayed gratification SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY MAY 01-03, 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Voon, Valerie; Brezing, Christina; Gallea, Cecile; Skaljic, Meliha; Hallett, Mark] NINDS, NIH, Bethesda, MD 20892 USA. [Reynolds, Brady] Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. [Potenza, Marc] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Dolan, Raymond J.] UCL, Wellcome Trust Ctr Neuroimaging, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 46 BP 16S EP 16S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700048 ER PT J AU Crowe, SL Naftalin, IT Blair, KS McCaffrey, D Vythilingam, M Pine, DS Blair, RJR AF Crowe, Samantha L. Naftalin, Ilana T. Blair, Karina S. McCaffrey, Dan Vythilingam, Meena Pine, Daniel S. Blair, R. J. R. TI Neural underpinnings of biased emotional attention in post-traumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Crowe, Samantha L.; Naftalin, Ilana T.; Blair, Karina S.; McCaffrey, Dan; Vythilingam, Meena; Pine, Daniel S.; Blair, R. J. R.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 65 BP 21S EP 22S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700067 ER PT J AU Mellman, TA Alim, T Ducci, F Buzas, B Goldman, D Lawson, WB Charney, D AF Mellman, Thomas A. Alim, Tanya Ducci, Francesca Buzas, Beata Goldman, David Lawson, William B. Charney, Dennis TI 5-HT2A promoter polymorphism and PTSD in an African American sample SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY MAY 01-03, 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Mellman, Thomas A.; Alim, Tanya; Lawson, William B.] Howard Univ, Washington, DC 20059 USA. [Ducci, Francesca; Buzas, Beata; Goldman, David] NIAA, LNG, Rockville, MD USA. [Charney, Dennis] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 63 BP 21S EP 21S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700065 ER PT J AU Rich, BA Onelio, L Holroyd, T Carver, F Pine, D Coppola, R Leibenluft, E AF Rich, Brendan A. Onelio, Laura Holroyd, Tom Carver, Frederick Pine, Daniel Coppola, Richard Leibenluft, Ellen TI The neural mechanisms of irritability in pediatric bipolar disorder: A magnetoencephalography (MEG) study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Rich, Brendan A.; Onelio, Laura; Holroyd, Tom; Carver, Frederick; Pine, Daniel; Coppola, Richard; Leibenluft, Ellen] NIMH, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 76 BP 25S EP 25S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700078 ER PT J AU Savitz, J van der Merwe, L Stein, DJ Solms, M Ramesar, R AF Savitz, Jonathan van der Merwe, Lize Stein, Dan J. Solms, Mark Ramesar, Rajkumar TI Bipolar I patients with and without a history of psychosis are most clearly differentiated by degree of working memory impairment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Savitz, Jonathan] NIMH, MAP MIB, NIH, Bethesda, MD 20892 USA. [van der Merwe, Lize] MRC South Africa, Biostat Unit, Cape Town, South Africa. [Stein, Dan J.; Solms, Mark; Ramesar, Rajkumar] Univ Cape Town, ZA-7925 Cape Town, South Africa. RI Ramesar, Raj/I-6941-2015; Stein, Dan/A-1752-2008 OI Ramesar, Raj/0000-0001-5688-1634; Stein, Dan/0000-0001-7218-7810 NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 77 BP 25S EP 25S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700079 ER PT J AU Schulze, TG Georgi, A Schmael, C Strohmaier, J Schirmbeck, F Boesshenz, K Schwarz, M Nothen, MM Rietsche, M AF Schulze, Thomas G. Georgi, Alexander Schmael, Christine Strohmaier, Jana Schirmbeck, Frederike Boesshenz, Katja Schwarz, Markus Noethen, Markus M. Rietsche, Marcella TI Social adjustment during childhood and adolescence: Bipolar patients outperform healthy controls premorbidly SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Georgi, Alexander; Schmael, Christine; Strohmaier, Jana; Schirmbeck, Frederike; Boesshenz, Katja; Rietsche, Marcella] CIMH, Mannheim, Germany. [Schulze, Thomas G.] NIMH, MAPGenet, Bethesda, MD 20892 USA. [Schwarz, Markus] PZN, Wiesloch, Germany. [Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, D-5300 Bonn, Germany. RI Schulze, Thomas/H-2157-2013; Schirmbeck, Frederike/G-8187-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 92 BP 30S EP 30S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700094 ER PT J AU Insel, T AF Insel, Thomas TI NIH update SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Insel, Thomas] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 106 BP 34S EP 34S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700108 ER PT J AU Drevets, WC AF Drevets, Wayne C. TI Neural circuits underlying anhedonia in major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Drevets, Wayne C.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 110 BP 35S EP 35S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700112 ER PT J AU Bondy, B Bedarida, G Born, C Rupprecht, R von Schacky, C Baghai, TC Saavedra, JM Johnson, AK Domschke, K Murck, H AF Bondy, Brigitta Bedarida, Gabriella Born, Christoph Rupprecht, Rainer von Schacky, Clemens Baghai, Thomas C. Saavedra, Juan M. Johnson, Alan Kim Domschke, Katharina Murck, Harald TI Brain-adrenal-kidney axis: The interaction of cardiovascular, electrolyte and mood regulation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Bondy, Brigitta; Born, Christoph; Rupprecht, Rainer; Baghai, Thomas C.] Univ Munich, Psychiat Clin, Munich, Germany. [Bedarida, Gabriella; von Schacky, Clemens] Univ Munich, Clin Internal Med, Munich, Germany. [Saavedra, Juan M.] NIMH, Bethesda, MD 20892 USA. [Johnson, Alan Kim] Univ Iowa, Iowa City, IA USA. [Domschke, Katharina] Univ Munster, Dept Psychiat, Munster, Germany. [Murck, Harald] Novartis Pharmaceut, E Hanover, NJ USA. RI Domschke, Katharina/I-7921-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 115 BP 37S EP 37S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700117 ER PT J AU Manji, H Kupfer, DJ Kogan, J AF Manji, Husseini Kupfer, David J. Kogan, Jane TI Career development institute (CDI) for bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Kupfer, David J.; Kogan, Jane] Univ Pittsburgh, Pittsburgh, PA USA. [Manji, Husseini] NIMH, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 116 BP 37S EP 37S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700118 ER PT J AU Lau, JYF Nelson, EE Lissek, S Grillon, C Goldwin, MA Ernst, M Pine, DS AF Lau, Jennifer Y. F. Nelson, Eric E. Lissek, Shmuel Grillon, Christian Goldwin, Michelle A. Ernst, Monique Pine, Daniel S. TI Developmental differences in neural correlates of human fear conditioning and extinction SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Lau, Jennifer Y. F.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [Nelson, Eric E.; Lissek, Shmuel; Grillon, Christian; Goldwin, Michelle A.; Ernst, Monique; Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA. RI Lissek, Shmuel/B-6577-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 117E BP 39S EP 39S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700123 ER PT J AU Hasler, G Fromm, S Carlson, PJ Luckenbaugh, DA Waldeck, T Geraci, M Roiser, JP Neumeister, A Meyers, N Charney, DS Drevets, WC AF Hasler, Gregor Fromm, Stephen Carlson, Paul J. Luckenbaugh, David A. Waldeck, Tracy Geraci, Marilla Roiser, Jonathan P. Neumeister, Alexander Meyers, Noah Charney, Dennis S. Drevets, Wayne C. TI Neural correlates of catecholaminergic dysfunction as a trait abnormality in major depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Fromm, Stephen; Carlson, Paul J.; Meyers, Noah; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. [Luckenbaugh, David A.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Waldeck, Tracy; Geraci, Marilla] NIMH, Ctr Clin, Bethesda, MD 20892 USA. [Roiser, Jonathan P.] Inst Neurol, Dept Imaging Neurosci, London WC1N 3BG, England. [Neumeister, Alexander] Yale Univ, Sch Med, Mol Imaging Program, New Haven, CT USA. [Charney, Dennis S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Hasler, Gregor] Univ Zurich Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland. RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 118C BP 40S EP 41S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700127 ER PT J AU Hardin, MG AF Hardin, Michael G. TI Emotion and incentive related modulation of cognitive control in adolescent anxiety SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Hardin, Michael G.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 119C BP 43S EP 43S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700133 ER PT J AU Dudek, SM AF Dudek, Serena M. TI Activity-dependent synapse elimination in hippocampal neurons SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Dudek, Serena M.] NIEHS, NIH, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 126 BP 46S EP 46S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700143 ER PT J AU Hyde, TM AF Hyde, Thomas M. TI Cation chloride co-transporters in human brain development and schizophrenia: NKCC1 and KCC2 SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Hyde, Thomas M.] NIMH, Sect Neuropathol, Clin Brain Disorders Branch, GCAP,Intramural Res Program, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 130 BP 47S EP 47S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700147 ER PT J AU Lipska, BK AF Lipska, Barbara K. TI Schizophrenia susceptibility and related genes across the lifespan: Results from qRT-PCR and microarrays SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Lipska, Barbara K.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 129 BP 47S EP 47S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700146 ER PT J AU Schmidt, P Rubinow, D AF Schmidt, Peter Rubinow, David TI Reproductive aging, hypogonadism, and behavior in women SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Schmidt, Peter] NIMH, Bethesda, MD 20892 USA. [Rubinow, David] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 136 BP 49S EP 49S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700153 ER PT J AU Chen, G AF Chen, Guang TI Selected hippocampal MicroRNAs are differentially regulated by chronic stress and mood stabilizers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Chen, Guang] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 151 BP 53S EP 53S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700168 ER PT J AU Kaplan, BB AF Kaplan, Barry B. TI Modulation of mRNA levels in the axon and presynaptic nerve terminal: Involvement of micro RNAs SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Kaplan, Barry B.] NIMH, Div Intramural Res Programs, Mol Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 150 BP 53S EP 53S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700167 ER PT J AU Jansma, JM Hakimi, S Tong, Y Zink, CF Meyer-Lindenberg, A AF Jansma, Johan M. Hakimi, Shabnarn Tong, Yonxia Zink, Caroline F. Meyer-Lindenberg, Andreas TI Trial by trial interaction effects in visual cortex and amygdala: Application of an fMRI method sensitive for non-linear effects SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Jansma, Johan M.; Hakimi, Shabnarn; Tong, Yonxia; Zink, Caroline F.; Meyer-Lindenberg, Andreas] NIMH, NIH, Bethesda, MD 20892 USA. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 155 BP 54S EP 55S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700172 ER PT J AU Erickson, K Brietberg, A Wood, SE Schulkin, J Drevets, WC AF Erickson, Kristine Brietberg, Alaina Wood, Suzanne E. Schulkin, Jay Drevets, Wayne C. TI Increased plasma cortisol differentially influences emotional processing in males and females SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Erickson, Kristine; Brietberg, Alaina; Wood, Suzanne E.; Schulkin, Jay; Drevets, Wayne C.] NIMH, MAP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 165 BP 57S EP 57S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700182 ER PT J AU Martinowich, K Schloesser, R Lu, Y Lu, B Nagappan, G Manji, H AF Martinowich, Keri Schloesser, Robert Lu, Yuan Lu, Bai Nagappan, Guhan Manji, Husseini TI A role for proBDNF and downstream p75NTR signaling in anxiogenic behaviors SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Martinowich, Keri; Schloesser, Robert; Lu, Yuan; Lu, Bai; Nagappan, Guhan; Manji, Husseini] Natl Inst Hlth, Mood & Anxiety Disorders Program, Bethesda, MD USA. RI Lu, Bai/A-4018-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 172 BP 59S EP 59S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700189 ER PT J AU Salloum, JB Saad, Z Bodurka, J Rio, D Rawlings, R Hommer, DW AF Salloum, Jasmin B. Saad, Ziad Bodurka, Jerzy Rio, Daniel Rawlings, Robert Hommer, Daniel W. TI Gender differences in fusiform gyrus response relative to arousal condition SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Salloum, Jasmin B.; Rio, Daniel; Rawlings, Robert; Hommer, Daniel W.] NIAAA, NIH, Bethesda, MD 20892 USA. [Saad, Ziad; Bodurka, Jerzy] NIMH, NIH, DIRP, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 178 BP 61S EP 61S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700195 ER PT J AU Schechter, JC Marsh, AA Fowler, KA Sinclair, S Pine, DS Blair, RJR AF Schechter, Julia C. Marsh, Abigail A. Fowler, Katie A. Sinclair, Stephen Pine, Daniel S. Blair, R. J. R. TI Psychopathic tendencies: Reduced emotional responsiveness or anomalous attentional control? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Schechter, Julia C.; Marsh, Abigail A.; Fowler, Katie A.; Sinclair, Stephen; Blair, R. J. R.] NIMH, Unit Affect & Cognit Neurosci, Bethesda, MD 20892 USA. [Pine, Daniel S.] NIMH, Sect Dev, Bethesda, MD 20892 USA. [Pine, Daniel S.] NIMH, Sect Affect Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 179 BP 61S EP 61S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700196 ER PT J AU Wang, Y Du, J Wei, Y Machado-Vieira, R Malkesman, O Chen, G Manji, HK AF Wang, Yun Du, Jing Wei, Yanling Machado-Vieira, Rodrigo Malkesman, Oz Chen, Guang Manji, Husseini K. TI GSK-3 beta modulates AMPA receptor internalization and synaptic plasticity: Relevance for mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Wang, Yun; Du, Jing; Wei, Yanling; Machado-Vieira, Rodrigo; Malkesman, Oz; Chen, Guang; Manji, Husseini K.] NIMH, Natl Inst Hlth, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Chen, Guang/A-2570-2017 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 182 BP 62S EP 62S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700199 ER PT J AU Wu, CC Crowe, SL Mitchell, DGV Blair, RJR AF Wu, Charlene C. Crowe, Samantha L. Mitchell, Derek G. V. Blair, R. J. R. TI Automatic or attentional control? Neural response to emotional expressions SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Wu, Charlene C.; Crowe, Samantha L.; Mitchell, Derek G. V.; Blair, R. J. R.] NIMH, Unit Affect Cognit Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 183 BP 62S EP 63S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700200 ER PT J AU Yuan, P Baum, AE Zhou, R Wang, Y Laje, G McMahon, FJ Chen, G Manji, HK AF Yuan, Peixiong Baum, Amber E. Zhou, Rulun Wang, Yun Laje, Gonzalo McMahon, Francis J. Chen, Guang Manji, Husseini K. TI Bcl-2 Polymorphisms associated with mood disorders and antidepressant-responsiveness regulate bcl-2 gene expression and cellular resilience in human lymphoblastoid cell lines SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Yuan, Peixiong; Zhou, Rulun; Wang, Yun; Chen, Guang; Manji, Husseini K.] NIMH, NIH, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. [Baum, Amber E.; Laje, Gonzalo; McMahon, Francis J.] NIMH, NIH, Genet Basis Mood & Anxiety Disorders Unit, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 4 Z9 4 U1 2 U2 2 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 185 BP 63S EP 63S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700202 ER PT J AU Karlsson, RM Heilig, M Holmes, A AF Karlsson, Rose-Marie Heilig, Markus Holmes, Andrew TI Loss of glutamate transporter GLAST (EAAT1) causes locomotor hyperactivity and exaggerated responses to psychotomimetics SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Karlsson, Rose-Marie; Heilig, Markus; Holmes, Andrew] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 191 BP 65S EP 65S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700208 ER PT J AU Malkesman, O Tragon, T Chen, G Manji, HK AF Malkesman, Oz Tragon, Tyson Chen, Guang Manji, Husseini K. TI Do genetically-influenced alterations in GluR6 receptors underlie SSRI-induced dysphoric reactions in the young? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Malkesman, Oz; Tragon, Tyson; Chen, Guang; Manji, Husseini K.] NIMH, NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 194 BP 66S EP 66S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700211 ER PT J AU Belforte, JE Li, Y Kunos, G Nakazawa, K AF Belforte, Juan E. Li, Yuqing Kunos, George Nakazawa, Kazu TI NMDA receptor ablation in forebrain-restricted interneurons results in psychiatric-like behavior SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Belforte, Juan E.; Nakazawa, Kazu] NIMH, UGCB, Bethesda, MD 20892 USA. [Li, Yuqing] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [Kunos, George] NIAAA, Lab Physiol Studies, Bethesda, MD USA. RI Li, Yuqing/G-1596-2011 OI Li, Yuqing/0000-0003-1211-5529 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 198 BP 67S EP 67S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700215 ER PT J AU Pickens, CL Golden, SA Shaharn, Y AF Pickens, Charles L. Golden, Sam A. Shaharn, Yavin TI A novel procedure to study long-lasting incubation of conditioned fear in rats SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Pickens, Charles L.; Golden, Sam A.; Shaharn, Yavin] Natl Inst Drug Abuse, NIH, DHHS, Behav Neurosci Branch,Intramural Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 199 BP 67S EP 67S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700216 ER PT J AU Sanchez, MM Lyon, CK Boudreau, M Graff, A Noble, PL Plotsky, P Nemeroff, CB Winslow, JT AF Sanchez, Mar M. Lyon, Casie K. Boudreau, Mathew Graff, Anne Noble, Pamela L. Plotsky, Paul Nemeroff, Charles B. Winslow, James T. TI Effects of early life stress on physical growth, sleep and metabolism during puberty and adolescence: Studies in nonhuman primates SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Sanchez, Mar M.; Lyon, Casie K.; Boudreau, Mathew; Plotsky, Paul; Nemeroff, Charles B.] Emory Univ, Atlanta, GA 30322 USA. [Sanchez, Mar M.; Lyon, Casie K.; Boudreau, Mathew; Graff, Anne] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Noble, Pamela L.] NIMH, NIH, 3IRP Neurobiol Primate Core, Poolesville, MD USA. [Winslow, James T.] NIMH, NIH, IRP Neurobiol Primate Core, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 201 BP 68S EP 68S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700218 ER PT J AU Bronstein, JA Kohn, PD Berman, KF AF Bronstein, Joel A. Kohn, Philip D. Berman, Karen F. TI Time-resolved intersubject synchronous analysis of fMRI data: From static maps to dynamic movies SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Bronstein, Joel A.; Kohn, Philip D.; Berman, Karen F.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 210 BP 71S EP 71S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700227 ER PT J AU Coutlee, CG Roe, KV Mervis, CB Morris, CA Kohn, PD Kippenhan, JS Meyer-Lindenberg, A Berman, KF AF Coutlee, Christopher G. Roe, Katherine V. Mervis, Carolyn B. Morris, Colleen A. Kohn, Philip D. Kippenhan, J. Shane Meyer-Lindenberg, Andreas Berman, Karen F. TI The neural substrate of lexical access in Williams syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Coutlee, Christopher G.; Roe, Katherine V.; Kohn, Philip D.; Kippenhan, J. Shane; Meyer-Lindenberg, Andreas; Berman, Karen F.] NIMH, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. [Mervis, Carolyn B.] Univ Louisville, Dept Psychol & Brain Sci, Neurodev Sci Lab, Louisville, KY 40292 USA. [Morris, Colleen A.] Univ Nevada, Sch Med, Dept Pediat, Las Vegas, NV 89154 USA. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-6800 Mannheim, Germany. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 212 BP 71S EP 72S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700229 ER PT J AU Feyder, MT Mathur, P Bussey, TJ Saksida, LM Grant, SGN Holmes, A AF Feyder, Michael T. Mathur, Poonam Bussey, Timothy J. Saksida, Lisa M. Grant, Seth G. N. Holmes, Andrew TI Task-specific deficits in learning and memory following gene deletion of PSD-95 in mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Feyder, Michael T.; Mathur, Poonam; Holmes, Andrew] NIAAA, NIH, Rockville, MD 20852 USA. [Bussey, Timothy J.; Saksida, Lisa M.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. [Grant, Seth G. N.] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB2 3EB, England. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 216 BP 73S EP 73S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700233 ER PT J AU King, E Furman, D Meyer-Lindenberg, A Kohn, P Sarpal, D Roe, K Berman, KF AF King, Eric Furman, Daniella Meyer-Lindenberg, Andreas Kohn, Philip Sarpal, Deepak Roe, Katherine Berman, Karen F. TI Functional connectivity of amygdala and orbitofrontal cortex during social and nonsocial reversal measured with PET SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [King, Eric; Furman, Daniella; Meyer-Lindenberg, Andreas; Kohn, Philip; Sarpal, Deepak; Roe, Katherine; Berman, Karen F.] NIMH, NIH, CBDB, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. RI Sarpal, Deepak/O-5630-2014; Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 221 BP 74S EP 74S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700238 ER PT J AU Kippenhan, JS Padmanabhan, A Mervis, C Morris, C Meyer-Lindenberg, A Berman, KF AF Kippenhan, Jonathan S. Padmanabhan, Aarthi Mervis, Carolyn Morris, Colleen Meyer-Lindenberg, Andreas Berman, Karen F. TI Hippocampus-specific spatial normalization using optimized SPM parameters improves sensitivity of functional neuroimage group analyses in Williams syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Kippenhan, Jonathan S.; Padmanabhan, Aarthi; Meyer-Lindenberg, Andreas; Berman, Karen F.] NIMH, NIH, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. [Mervis, Carolyn] Univ Louisville, Dept Psychol & Brain Sci, Neurodev Sci Lab, Louisville, KY 40292 USA. [Morris, Colleen] Univ Nevada, Sch Med, Dept Pediat, Las Vegas, NV 89154 USA. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 1 TC 1 Z9 1 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 222 BP 74S EP 75S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700239 ER PT J AU Padmanabhan, A Kohn, PD Nichols, LM Kolachana, B Weinberger, DR Berman, KF AF Padmanabhan, Aarthi Kohn, Philip D. Nichols, Lisa M. Kolachana, Bhaskar Weinberger, Daniel R. Berman, Karen F. TI Effects of BDNF val(66)met genotype on regional cerebral blood flow and functional connectivity during working memory SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Padmanabhan, Aarthi; Kohn, Philip D.; Nichols, Lisa M.; Berman, Karen F.] NIMH, Sect Intergrat Neuroimaging, Bethesda, MD 20892 USA. [Kolachana, Bhaskar; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Gene Cognit & Psychosis Program, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 227 BP 76S EP 76S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700244 ER PT J AU Prust, MJ Tan, HY Gold, JM Mattay, VS Weinberger, DR Callicott, JH AF Prust, Morgan J. Tan, Hao Yang Gold, James M. Mattay, Venkata S. Weinberger, Daniel R. Callicott, Joseph H. TI Working memory capacity and individual response differences to increasing cognitive load SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Prust, Morgan J.; Tan, Hao Yang; Gold, James M.; Mattay, Venkata S.; Weinberger, Daniel R.; Callicott, Joseph H.] NIMH, Clin Brain Disorders Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 228 BP 76S EP 77S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700245 ER PT J AU Tong, YX Chen, Q Zink, C Kempf, L Mattay, V Weinberger, D Meyer-Lindenberg, A AF Tong, Yunxia Chen, Qiang Zink, Caroline Kempf, Lucas Mattay, Venkata Weinberger, Daniel Meyer-Lindenberg, Andreas TI Effective connectivity of brain regions within the emotion information processing network SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Tong, Yunxia; Chen, Qiang; Zink, Caroline; Kempf, Lucas; Mattay, Venkata; Weinberger, Daniel] NIMH, GCAP, Bethesda, MD 20892 USA. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-6800 Mannheim, Germany. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 234 BP 78S EP 79S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700251 ER PT J AU Greenwood, TA Light, GA Cadenhead, KS Freedman, R Green, MF Gur, RE Kelsoe, JR Murray, SS Nuechterlein, KH Olincy, A Radant, AD Schork, NJ Seidman, LJ Siever, LJ Silverman, JM Swerdlow, NR Tsuang, DW Turetsky, BI Weinberger, DR Braff, DL AF Greenwood, Tiffany A. Light, Gregory A. Cadenhead, Kristin S. Freedman, Robert Green, Michael F. Gur, Raquel E. Kelsoe, John R. Murray, Sarah S. Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Schork, Nicholas J. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Swerdlow, Neal R. Tsuang, Debby W. Turetsky, Bruce I. Weinberger, Daniel R. Braff, David L. TI Initial analyses of 94 candidate genes and twelve endophenotypes for schizophrenia from the consortium on the genetics of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Greenwood, Tiffany A.; Light, Gregory A.; Cadenhead, Kristin S.; Kelsoe, John R.; Swerdlow, Neal R.; Braff, David L.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Greenwood, Tiffany A.; Kelsoe, John R.] Univ Colorado, Hlth Sci Ctr, Hlth Care Syst, San Diego, CA USA. [Freedman, Robert; Olincy, Ann] Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. [Green, Michael F.; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gur, Raquel E.; Turetsky, Bruce I.] Univ Penn, Philadelphia, PA 19104 USA. [Murray, Sarah S.] Scripps, La Jolla, CA USA. [Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Seattle, WA 98195 USA. [Radant, Allen D.; Tsuang, Debby W.] Puget Sound Vet Adm, Hlth Care Syst, Seattle, WA USA. [Schork, Nicholas J.] Scripps Res Inst, La Jolla, CA USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr Publ Psychiat Div, Boston, MA USA. [Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, New York, NY USA. [Siever, Larry J.] James J Peters VA Med Ctr, New York, NY USA. [Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 247 BP 82S EP 83S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700264 ER PT J AU Nichols, L Mattay, V Callicott, J Kohn, P Kolachana, B Kippenhan, S Meyer-Lindenberg, A Hyde, T Weinberger, D Berman, K AF Nichols, Lisa Mattay, Venkata Callicott, Joseph Kohn, Philip Kolachana, Bhaskar Kippenhan, Shane Meyer-Lindenberg, Andreas Hyde, Thomas Weinberger, Daniel Berman, Karen TI Altered hippocampal function and connectivity during multiple tasks in cognitively healthy young apolipoprotein E epsilon 4 carriers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Nichols, Lisa; Kohn, Philip; Kippenhan, Shane; Berman, Karen] NIMH, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. [Nichols, Lisa; Mattay, Venkata; Callicott, Joseph; Kohn, Philip; Kolachana, Bhaskar; Kippenhan, Shane; Meyer-Lindenberg, Andreas; Hyde, Thomas; Weinberger, Daniel; Berman, Karen] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 252 BP 84S EP 84S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700269 ER PT J AU Wei, SM Roe, K Kohn, PD Padmanabhan, A Kolachana, B Weinberger, DR Berman, KF AF Wei, Shau-Ming Roe, Katherine Kohn, Philip D. Padmanabhan, Aarthi Kolachana, Bhaskar Weinberger, Daniel R. Berman, Karen F. TI Brain-derived neurotrophic factor val(66)met polymorphism differentially affects hippocampal regional cerebral blood flow during rest SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat ID HUMAN-MEMORY C1 [Wei, Shau-Ming; Roe, Katherine; Kohn, Philip D.; Padmanabhan, Aarthi; Kolachana, Bhaskar; Weinberger, Daniel R.; Berman, Karen F.] NIMH, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 254 BP 85S EP 85S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700271 ER PT J AU Lindell, SG Schwandt, ML Suomi, SJ Goldman, D Heilig, M Higley, JD Barr, CS AF Lindell, Stephen G. Schwandt, Melanie L. Suomi, Stephen J. Goldman, David Heilig, Markus Higley, J. D. Barr, Christina S. TI Variation in the rhNPY promoter region is associated with anxiety and behavioral pathology in infant rhesus macaques SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Lindell, Stephen G.; Schwandt, Melanie L.; Barr, Christina S.] NIAAA, LCTS, NIH, Poolesville, MD 20852 USA. [Suomi, Stephen J.] NICHD, LCE, NIH, Poolesville, MD USA. [Goldman, David] NIAAA, LNG, NIH, Rockville, MD USA. [Heilig, Markus] NIAAA, LCTS, NIH, Bethesda, MD USA. [Higley, J. D.] BYU, Provo, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 260 BP 87S EP 87S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700277 ER PT J AU Zhou, R Yuan, PX Wang, Y Elkahloun, A Damschroder-Williams, P Du, J Chen, G Manji, H AF Zhou, Rulun Yuan, Peixiong Wang, Yun Elkahloun, Abdel Damschroder-Williams, Patricia Du, Jing Chen, Guang Manji, Husseini TI Selective common targets for lithium and valproate are microRNAs involved in stress reaction SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Zhou, Rulun; Yuan, Peixiong; Wang, Yun; Damschroder-Williams, Patricia; Du, Jing; Chen, Guang; Manji, Husseini] NIMH, NIH, Bethesda, MD 20892 USA. [Elkahloun, Abdel] NHGRI, NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 265 BP 88S EP 88S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700282 ER PT J AU Basselin, M Rapoport, SI AF Basselin, Mireille Rapoport, Stanley I. TI The two mood stabilizers, valproic acid and carbamazepine block NMDA- and D2-like initiated brain signaling via arachidonic acid, respectively: Relevance to bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Basselin, Mireille; Rapoport, Stanley I.] NIA, Brain Physiol Metab Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 266 BP 89S EP 89S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700283 ER PT J AU Khairova, RA Wei, YL Du, J Manji, HK AF Khairova, Rushaniya A. Wei, Yanling Du, Jing Manji, Husseini K. TI The role of TNF-alpha in regulation of AMPA receptor subunit-specific trafficking in rat hippocampal neurons SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Khairova, Rushaniya A.; Wei, Yanling; Du, Jing; Manji, Husseini K.] NIH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 268 BP 89S EP 89S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700285 ER PT J AU Mickey, BJ Ducci, F David, G Zubieta, JK AF Mickey, Brian J. Ducci, Francesca David, Goldman Zubieta, Jon-Kar TI Monoamine oxidase a genotype predicts human serotonin 1A receptor availability in vivo SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Mickey, Brian J.; Zubieta, Jon-Kar] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Ducci, Francesca; David, Goldman] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 270 BP 90S EP 90S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700287 ER PT J AU Baller, EB Schmidt, PJ Kohn, PF Rubinow, DR Furman, DJ Berman, KF AF Baller, Erica B. Schmidt, Peter J. Kohn, Philip F. Rubinow, David R. Furman, Daniella J. Berman, Karen F. TI Neural correlates of hormonally modulated spatial cognition in women SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Baller, Erica B.; Kohn, Philip F.; Furman, Daniella J.; Berman, Karen F.] NIMH, CBDB, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. [Schmidt, Peter J.; Rubinow, David R.] NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 279 BP 93S EP 93S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700296 ER PT J AU Richards, AB Schmitz, S Ward, S Rothmond, D Noble, P Shannon, C Woodward, R Winslow, J AF Richards, A. Brent Schmitz, Stephanie Ward, Sarah Rothmond, Debora Noble, Pam Shannon, Cynthia Woodward, Ruth Winslow, James TI Effects of prepubertal gonadectomy on hypothalamic-pituitary-adrenal axis function in the rhesus macaque SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Richards, A. Brent; Ward, Sarah] NIMH, MiNDS Unit, Poolesville, MD USA. [Schmitz, Stephanie; Noble, Pam; Winslow, James] NIMH, Nonhuman Primate Core Facil, Poolesville, MD USA. [Rothmond, Debora; Shannon, Cynthia] Univ New S Wales, Neurosci Inst Schizophrenia & Allied Disorders, Randwick, NSW, Australia. [Woodward, Ruth] NICHHD, Res Anim Management Branch, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 283 BP 94S EP 94S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700300 ER PT J AU Schmitz, S Richards, AB Ward, S Rothmond, D Noble, P Winslow, J Woodward, R Weickert, CS AF Schmitz, Stephanie Richards, A. Brent Ward, Sarah Rothmond, Debora Noble, Pam Winslow, James Woodward, Ruth Weickert, Cynthia Shannon TI Removal of pubertal testosterone impacts social dominance and responsiveness to novelty in rhesus macaques SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Schmitz, Stephanie; Richards, A. Brent; Ward, Sarah; Noble, Pam; Winslow, James] NIMH, Non Human Primate Core Facil, Poolesville, MD USA. [Rothmond, Debora; Weickert, Cynthia Shannon] Univ New S Wales, Neurosci Inst Schizophrenia & Allied Disorders, Randwick, NSW, Australia. [Woodward, Ruth] NICHHD, Res Anim Management Branch, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 284 BP 94S EP 95S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700301 ER PT J AU Schloesser, RJ Martinowich, K Lednak, JB Chen, G Manji, HK AF Schloesser, Robert J. Martinowich, Keri Lednak, John-Brendan Chen, Guang Manji, Husseini K. TI Effects of valproic acid on adult hippocampal neurogenesis and behavior SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Schloesser, Robert J.; Martinowich, Keri; Lednak, John-Brendan; Chen, Guang; Manji, Husseini K.] NIMH, LMP, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 294 BP 97S EP 98S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700311 ER PT J AU Garg, K Manalai, P Stiller, J Hyde, T Kleinman, J Postolache, T Tonelli, LH AF Garg, Kawish Manalai, Partarn Stiller, John Hyde, Thomas Kleinman, Joel Postolache, Teodor Tonelli, Leonardo H. TI Corpora amylacea are not correlated with mast cells in the ventrolateral prefrontal cortex (VLPFC) of victims of suicide and controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Garg, Kawish; Manalai, Partarn; Postolache, Teodor; Tonelli, Leonardo H.] Univ Maryland, Baltimore, MD 21201 USA. [Stiller, John] St Elizabeth Hosp, Washington, DC USA. [Hyde, Thomas; Kleinman, Joel] NIMH, Sect Neuropathol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 297 BP 98S EP 98S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700314 ER PT J AU Bigos, KL Ferrell, RE Pollock, BG Fisher, PM Aizenstein, HJ Bies, RR Hariri, AR AF Bigos, Kristin L. Ferrell, Robert E. Pollock, Bruce G. Fisher, Patrick M. Aizenstein, Howard J. Bies, Robert R. Hariri, Ahmad R. TI Serotonin transporter polymorphic modulation of acute citalopram response SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Bigos, Kristin L.] Natl Inst Hlth, Clin Brain Disorders Branch, Bethesda, MD USA. [Ferrell, Robert E.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Pollock, Bruce G.] Univ Toronto, Rotman Res Inst, Toronto, ON, Canada. [Fisher, Patrick M.; Aizenstein, Howard J.; Hariri, Ahmad R.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Bies, Robert R.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA. RI Bigos, Kristin/E-9768-2010; Hariri, Ahmad/D-5761-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 300 BP 99S EP 99S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700317 ER PT J AU Chen, YC Holmes, A AF Chen, Yi-Chyan Holmes, Andrew TI Topiramate enhances ethanol sensitivity and augments NMDA receptor antagonist-mediated potentiation of ethanol intoxication in mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Chen, Yi-Chyan] Natl Def Med Ctr, Dept Psychiat, Tri Serv Gen Hosp, Taipei, Taiwan. [Chen, Yi-Chyan; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 303 BP 100S EP 100S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700320 ER PT J AU Chen, SA Schwandt, ML Lindell, SG Lopez-Coleman, N Peele, LN Woodward, RA Robbins, KL Suomi, SJ Heilig, MA Barr, CS AF Chen, Scott A. Schwandt, Melanie L. Lindell, Stephen G. Lopez-Coleman, Nina Peele, Lauren N. Woodward, Ruth A. Robbins, Kathlyn L. Suomi, Stephen J. Heilig, Markus A. Barr, Christina S. TI Effects of a corticotropin releasing factor receptor 1 antagonist on acute stress-induced behaviors in rhesus macaques SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Chen, Scott A.; Schwandt, Melanie L.; Lindell, Stephen G.; Lopez-Coleman, Nina; Peele, Lauren N.; Heilig, Markus A.; Barr, Christina S.] NIAAA, Lab Clin & Translat Studies, NIH, Poolesville, MD USA. [Woodward, Ruth A.] NICHD, Res Anim Management Branch, NIH, Poolesville, MD USA. [Robbins, Kathlyn L.; Suomi, Stephen J.] NICHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 304 BP 101S EP 101S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700321 ER PT J AU Machado-Vieira, R AF Machado-Vieira, Rodrigo TI Bcl-2-mediated mitochondrial calcium dynamics in neurons: Role in the treatment of bipolar disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Machado-Vieira, Rodrigo] NIMH, Lab Mol Psychiat, NIH, Bethesda, MD 20892 USA. RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 318 BP 105S EP 105S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700335 ER PT J AU Barr, CS Dvoskin, RL Schwandt, ML Lindell, SG Kling, MA Gold, PW Higley, JD Heilig, M Suomi, SJ Goldman, D AF Barr, Christina S. Dvoskin, Rachel L. Schwandt, Melanie L. Lindell, Stephen G. Kling, Mitchel A. Gold, Phillip W. Higley, J. Dee Heilig, Markus Suomi, Stephen J. Goldman, David TI CRH haplotype predicts CSFCRH, HPA axis activity, temperament, and alcohol consumption in rhesus macaques SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Barr, Christina S.; Dvoskin, Rachel L.; Schwandt, Melanie L.; Lindell, Stephen G.; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Poolesville, MD USA. [Kling, Mitchel A.] Wyeth Ayerst Res, Collegeville, PA USA. [Gold, Phillip W.] NIMH, Clin Neuroendocrinol Branch, DIR, NIH, Bethesda, MD 20892 USA. [Higley, J. Dee] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Suomi, Stephen J.] NICHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. [Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 329 BP 108S EP 108S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700346 ER PT J AU Graybeal, C Mathur, P Feyder, M Holmes, A AF Graybeal, Carolyn Mathur, Poonam Feyder, Michael Holmes, Andrew TI Contribution of NR2B-containing NMDA receptors to fear learning is lost with aging and stress SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Graybeal, Carolyn; Mathur, Poonam; Feyder, Michael; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 335 BP 110S EP 110S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700352 ER PT J AU Jenness, JL AF Jenness, Jessica L. TI The effects of early maltreatment on reward processing in adolescents SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Jenness, Jessica L.] NIMH, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 337 BP 110S EP 111S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700354 ER PT J AU Bellgowan, JAF Drevets, WC Opal, MD Khanna, A Furey, ML AF Bellgowan, Julie A. Frost Drevets, Wayne C. Opal, Mark D. Khanna, Ashish Furey, Maura L. TI Interactions between attention and emotional processing in major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Bellgowan, Julie A. Frost; Drevets, Wayne C.; Opal, Mark D.; Khanna, Ashish; Furey, Maura L.] NIMH, Sect Mood Disorders & Anxiety, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 345 BP 114S EP 114S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700362 ER PT J AU Laje, G Cannon, DM Allen, AS Liu, XM Manji, HK Drevets, W McMahon, FJ AF Laje, Gonzalo Cannon, Dara M. Allen, Andrew S. Liu, Xinmin Manji, Husseini K. Drevets, Wayne McMahon, Francis J. TI HTR2A associates with serotonin transporter binding assessed using [C-11]DASB and positron emission tomography SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Laje, Gonzalo; Liu, Xinmin; McMahon, Francis J.] NIMH, Bethesda, MD 20892 USA. [Cannon, Dara M.; Drevets, Wayne] Mol Imaging Branch, Bethesda, MD USA. [Allen, Andrew S.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 347 BP 114S EP 115S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700364 ER PT J AU Savitz, J Neurneister, A Nugent, A Bogers, W Goldman, D Drevets, W AF Savitz, Jonathan Neurneister, Alex Nugent, Allison Bogers, Wendy Goldman, David Drevets, Wayne TI Subgenual prefrontal cortex volume in affective illness: The impact of the serotonin transporter gene length polymorphism. SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Savitz, Jonathan; Nugent, Allison; Bogers, Wendy; Drevets, Wayne] NIMH, MAP, MIB, NIH, Bethesda, MD 20892 USA. [Neurneister, Alex] Yale Univ, Sch Med, New Haven, CT USA. [Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 346 BP 114S EP 114S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700363 ER PT J AU Martin-Soelch, C Szczepanik, J Barhaghi, K Rollis, D Cannon, D Nugent, A Herscovitsch, P Drevets, W AF Martin-Soelch, Chantal Szczepanik, Joanna Barhaghi, Krystle Rollis, Denise Cannon, Dara Nugent, Alison Herscovitsch, Peter Drevets, Wayne TI Lack of dopamine release in response to monetary reward in depressed patients: An 11C-raclopride bolus plus constant infusion PET-study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Martin-Soelch, Chantal] Univ Zurich Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland. [Szczepanik, Joanna; Barhaghi, Krystle; Rollis, Denise; Nugent, Alison; Drevets, Wayne] NIMH, Mood & Anxiety Disorders Programm, Bethesda, MD 20892 USA. [Cannon, Dara] Natl Univ Ireland Univ Coll Galway, Dept Psychiat, Galway, Ireland. [Herscovitsch, Peter] NIH, PET Dept, Bethesda, MD USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 351 BP 116S EP 116S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700368 ER PT J AU Voon, V Gallea, C Ekanayake, V Hattori, N Bruno, M Kansaku, K Hallett, M AF Voon, Valerie Gallea, Cecile Ekanayake, Vindhya Hattori, Noriaki Bruno, Michiko Kansaku, Kenji Hallett, Mark TI Loss of motor-limbic functional connectivity in conversion disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Voon, Valerie; Gallea, Cecile; Ekanayake, Vindhya; Hattori, Noriaki; Bruno, Michiko; Kansaku, Kenji; Hallett, Mark] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 356 BP 118S EP 118S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700373 ER PT J AU Oquendo, MA Currier, D Hasin, D Grant, BF Blanco, C AF Oquendo, Maria A. Currier, Dianne Hasin, Deborah Grant, Bridget F. Blanco, Carlos TI Increased risk for suicdial behavior in comorbid bipolar disorder and alcohol use disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Oquendo, Maria A.; Currier, Dianne; Hasin, Deborah; Blanco, Carlos] Columbia Univ, New York, NY USA. [Grant, Bridget F.] NIAAA, Rockville, MD 20852 USA. RI Blanco, Carlos/I-4906-2013 OI Blanco, Carlos/0000-0001-6187-3057 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 405 BP 133S EP 133S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700422 ER PT J AU Furey, ML AF Furey, Maura L. TI The influence of muscarinic cholinergic receptors on mood, attention and emotional stimulus processing in affective disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Furey, Maura L.] NIMH, Bethesda, MD 20892 USA. [Furey, Maura L.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 418 BP 136S EP 136S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700435 ER PT J AU Laje, G Trivedi, MH Gibbons, RD Laughren, TP AF Laje, Gonzalo Trivedi, Madhukar H. Gibbons, Robert D. Laughren, Thomas P. TI Controversies surrounding antidepressants and suicide SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Laje, Gonzalo] NIMH, NIH, Bethesda, MD 20892 USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Gibbons, Robert D.] Univ Illinois, Chicago, IL USA. [Laughren, Thomas P.] CBER Food & Drug Adm, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 450 BP 145S EP 145S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700466 ER PT J AU Barenboim, M Hyde, TM Kleinman, JE Lipska, BK Weinberger, DR AF Barenboim, Maxim Hyde, Thomas M. Kleinman, Joel E. Lipska, Barbara K. Weinberger, Daniel R. TI Computational prediction of 3 ' UTR SNP effect on expression of COMT emphasizes the role of its rare transcript SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Barenboim, Maxim; Hyde, Thomas M.; Kleinman, Joel E.; Lipska, Barbara K.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 475 BP 152S EP 152S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700485 ER PT J AU Craig, DW Szelinger, S Josephson, M Potash, J Gershon, ES Edenberg, HJ Coryell, W Scheftner, W Lawson, W Byerley, W Rice, JR McMahon, FJ Berrettini, W Nurnberger, J Kelsoel, JR AF Craig, David W. Szelinger, Szabolcs Josephson, Margot Potash, James Gershon, Elliot S. Edenberg, Howard J. Coryell, William Scheftner, William Lawson, William Byerley, William Rice, John R. McMahon, Francis J. Berrettini, Wade Nurnberger, John Kelsoel, John R. TI Genome-wide association study of bipolar disorder and meta-analysis with existing genetic association studies supports several previous candidates and identifies new genes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY MAY 01-03, 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Craig, David W.; Szelinger, Szabolcs; Josephson, Margot] TGen, Phoenix, AZ USA. [Potash, James] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. [Gershon, Elliot S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Edenberg, Howard J.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA. [Coryell, William] Univ Iowa, Dept Psychiat, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA. [Scheftner, William] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. [Lawson, William] Howard Univ, Dept Psychiat, Washington, DC 20059 USA. [Byerley, William] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Rice, John R.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Berrettini, Wade] Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. [Nurnberger, John] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA. [Kelsoel, John R.] Univ San Diego, Dept Psychiat, San Diego, CA 92110 USA. [McMahon, Francis J.] NIMH, Unit Genet Basis Mood & Anxiety Disorders 11, Mood & Anxiety Disorders Program, US Dept HHS,NIH, Bethesda, MD 20892 USA. RI McMahon, Francis/A-7290-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 476 BP 152S EP 153S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700486 ER PT J AU Maheu, FS Dozier, M Mandell, D Peloso, E Poeth, K Jenness, J Lau, JYF Fromm, S Pine, DS Ernst, M AF Maheu, Francoise S. Dozier, Mary Mandell, Darcy Peloso, Elizabeth Poeth, Kaitlin Jenness, Jessica Lau, Jennifer Y. F. Fromm, Stephen Pine, Daniel S. Ernst, Monique TI Early adversity modulation of amygdala response to negative emotional faces in adopted maltreated adolescents SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Maheu, Francoise S.; Mandell, Darcy; Poeth, Kaitlin; Jenness, Jessica; Fromm, Stephen; Pine, Daniel S.; Ernst, Monique] NIMH, Emot Dev & Affect Neurosci Branch, Bethesda, MD 20892 USA. [Dozier, Mary; Peloso, Elizabeth] Univ Delaware, Dept Psychol, Newark, DE USA. [Lau, Jennifer Y. F.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 474 BP 152S EP 152S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700484 ER PT J AU Weinberger, D AF Weinberger, Daniel TI The GABA hypothesis of schizophrenia: From basic science to clinical trials SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Weinberger, Daniel] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 483 BP 155S EP 155S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700493 ER PT J AU Weinberger, D AF Weinberger, Daniel TI Schizophrenia and bipolar disorder: Pleotropic effects in brain of shared susceptibility genes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Weinberger, Daniel] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 489 BP 156S EP 156S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700499 ER PT J AU Fujita, M Pike, VW Innis, RB AF Fujita, Masahiro Pike, Victor W. Innis, Robert B. TI Positron emission tomography imaging of the peripheral benzodiazepine receptor, a potential biomarker for neuroinflammation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Fujita, Masahiro; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 501 BP 160S EP 160S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700511 ER PT J AU Siever, LJ Ducci, F Hodgkinson, CA New, AS Koenigsberg, HW Goodman, M Goldman, D AF Siever, Larry J. Ducci, Francesca Hodgkinson, Colin A. New, Antonia S. Koenigsberg, Harold W. Goodman, Marianne Goldman, David TI Genotypes and endophenotypes in borderline personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Siever, Larry J.; New, Antonia S.; Koenigsberg, Harold W.; Goodman, Marianne] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.; New, Antonia S.; Koenigsberg, Harold W.; Goodman, Marianne] Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. [Ducci, Francesca; Hodgkinson, Colin A.; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 505 BP 161S EP 161S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700515 ER PT J AU Mandell, DL Hardin, MG Muller, SC Pine, DS Ernst, M AF Mandell, Darcy L. Hardin, Michael G. Muller, Sven C. Pine, Daniel S. Ernst, Monique TI Reward related modulation of response inhibition: Validation of methods during neuroimaging SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Mandell, Darcy L.; Hardin, Michael G.; Muller, Sven C.; Pine, Daniel S.; Ernst, Monique] NIMH, Emot Dev & Affect Neurosci Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 511 BP 163S EP 163S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700521 ER PT J AU Schwandt, ML Lindell, SG Higley, JD Suomi, SJ Barr, CS AF Schwandt, Melanie L. Lindell, Stephen G. Higley, J. Dee Suomi, Stephen J. Barr, Christina S. TI Rearing condition and serotonin transporter gene variation interact to influence aggressive behavior in response to an unfamiliar intruder in rhesus macaques SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Schwandt, Melanie L.; Lindell, Stephen G.; Barr, Christina S.] NIAAA, NIH, LCTS, Poolesville, MD USA. [Higley, J. Dee] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Barr, Christina S.] NICHD, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 515 BP 164S EP 164S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700525 ER PT J AU Carlson, PJ Neurneister, A Tinsley, R Geraci, M Kaplan, J Nugent, A Luckenbaugh, D Pine, D Charney, D Drevets, WC AF Carlson, Paul J. Neurneister, Alex Tinsley, Ruth Geraci, Marilla Kaplan, Johanna Nugent, Allison Luckenbaugh, David Pine, Daniel Charney, Dennis Drevets, Wayne C. TI Prefrontal-limbic circuitry alterations in yohimbine-induced panic attacks SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Carlson, Paul J.; Tinsley, Ruth; Geraci, Marilla; Kaplan, Johanna; Nugent, Allison; Luckenbaugh, David; Pine, Daniel; Drevets, Wayne C.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Neurneister, Alex] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Charney, Dennis] Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 534 BP 170S EP 170S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700544 ER PT J AU Enoch, MA Shen, PH Ducci, F Yuan, Q White, KV Albaugh, B Hodgkinson, C Goldman, D AF Enoch, Mary-Anne Shen, Pei-Hong Ducci, Francesca Yuan, Qiaoping White, Kenneth V. Albaugh, Bernard Hodgkinson, Colin Goldman, David TI Association between CRH-BP and alcoholism, anxiety and EEG power in two populations SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Albaugh, Bernard] Ctr Human Behav Studies, Weatherford, OK USA. [Enoch, Mary-Anne; Shen, Pei-Hong; Ducci, Francesca; Yuan, Qiaoping; White, Kenneth V.; Hodgkinson, Colin; Goldman, David] NIAAA, NIH, LNG, Bethesda, MD USA. RI Hodgkinson, Colin/F-9899-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 537 BP 171S EP 171S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700547 ER PT J AU Hollon, NG Devido, J Jones, M Geraci, M Blair, J Pine, DS Blair, KS AF Hollon, Nick G. Devido, Jeffrey Jones, Matthew Geraci, Marilla Blair, James Pine, Daniel S. Blair, Karina S. TI Optimistic bias in generalized anxiety disorder (GAD) and generalized social phobia (GSP) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Hollon, Nick G.; Devido, Jeffrey; Jones, Matthew; Geraci, Marilla; Blair, James; Pine, Daniel S.; Blair, Karina S.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 548 BP 175S EP 175S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700558 ER PT J AU Temple, VA Hardin, MG Pine, DS Ernst, M AF Temple, Veronica A. Hardin, Michael G. Pine, Daniel S. Ernst, Monique TI Influence of 5HTT serotonin transporter gene and adolescent anxiety on response inhibition: Preliminary results SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Temple, Veronica A.; Hardin, Michael G.; Pine, Daniel S.; Ernst, Monique] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 560 BP 179S EP 179S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700570 ER PT J AU Williams, AE Lau, JYF Temple, VA Pine, DS Ernst, M AF Williams, Amber E. Lau, Jen Y. F. Temple, Veronica A. Pine, Daniel S. Ernst, Monique TI Gene expression of the neuropeptide Y (NPY) gene and prediction of pediatric anxiety symptoms reported on child and parent version of screen for child anxiety related emotional disorders (scared) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY MAY 01-03, 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Williams, Amber E.; Lau, Jen Y. F.; Temple, Veronica A.; Pine, Daniel S.; Ernst, Monique] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 562 BP 179S EP 180S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700572 ER PT J AU Brotman, MA Skup, M Rich, BA Pine, DS Blair, KS Blair, JR Leibenluft, E AF Brotman, Melissa A. Skup, Martha Rich, Brendan A. Pine, Daniel S. Blair, Karina S. Blair, James R. Leibenluft, Ellen TI Non-specific face emotion labeling deficits in youth at risk for bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Brotman, Melissa A.; Skup, Martha; Rich, Brendan A.; Pine, Daniel S.; Blair, Karina S.; Blair, James R.; Leibenluft, Ellen] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Brotman, Melissa/H-7409-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 568 BP 181S EP 181S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700578 ER PT J AU Liu, XM Cannon, DM Drevets, W McMahon, FJ AF Liu, Xinmin Cannon, Dara M. Drevets, Wayne McMahon, Francis J. TI Genome-wide association study of PET scan phenotypes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Liu, Xinmin; McMahon, Francis J.] NIMH, Unit Genet Basis Mood & Anxiety Disorders Program, NIH, Bethdsda, MD USA. [Cannon, Dara M.; Drevets, Wayne] NIMH, Sect Neuroimaging Mood & Anxiety Disorders Progra, NIH, Bethdsda, MD USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 583 BP 186S EP 186S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700593 ER PT J AU Mallinger, AG Frank, E Thase, ME Barwell, MM Kupfer, DJ AF Mallinger, Alan G. Frank, Ellen Thase, Michael E. Barwell, Michelle M. Kupfer, David J. TI Revisiting the effectiveness of antidepressants in bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Mallinger, Alan G.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Mallinger, Alan G.; Frank, Ellen; Thase, Michael E.; Barwell, Michelle M.; Kupfer, David J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 586 BP 186S EP 187S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700596 ER PT J AU Nugent, AC Bain, EE Thayer, JF Sollers, JJ Drevets, WC AF Nugent, Allison C. Bain, Earle E. Thayer, Julian F. Sollers, John J. Drevets, Wayne C. TI Alterations in neural correlates of autonomic control in females with major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Nugent, Allison C.; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. [Bain, Earle E.] Abbott Pharmacut, Neurosci & Anesthesia Dev, Abbott Pk, IL USA. [Thayer, Julian F.; Sollers, John J.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 662 BP 210S EP 210S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700672 ER PT J AU Phelps, LE Moral, J Brutsche, N Luckenbaugh, DA Manji, HK Zarate, C AF Phelps, Laura E. Moral, Jazmin Brutsche, Nancy Luckenbaugh, David A. Manji, Husseini K. Zarate, Carlos TI Family history of alcohol dependence predicts initial antidepressant response to an NMDA antagonist SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Phelps, Laura E.; Moral, Jazmin; Brutsche, Nancy; Luckenbaugh, David A.; Manji, Husseini K.; Zarate, Carlos] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 664 BP 211S EP 211S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700674 ER PT J AU Salvadore, G Cornwe, BR Colon-Rosario, V Grillon, C Zarate, CA Manji, HK AF Salvadore, Giacomo Cornwe, Brian R. Colon-Rosario, Veronica Grillon, Christian Zarate, Carlos A. Manji, Husseini K. TI Impaired hippocampal function in major depression: A magnetoencephalographic study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Salvadore, Giacomo; Colon-Rosario, Veronica; Zarate, Carlos A.; Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. [Cornwe, Brian R.; Grillon, Christian] NIMH, Lab Affect Psychophysiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 670 BP 213S EP 213S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700680 ER PT J AU Schaefer, K Fantie, BD Luckenbaugh, DA Manji, H Zarate, C AF Schaefer, Kathryn Fantie, Bryan D. Luckenbaugh, David A. Manji, Husseini Zarate, Carlos TI Face emotion labeling deficits in depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Schaefer, Kathryn; Luckenbaugh, David A.; Manji, Husseini; Zarate, Carlos] Natl Inst Hlth, Mood & Anxiety Disorders Program, Bethesda, MD USA. [Fantie, Bryan D.] Natl Inst Drug Abuse, Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 671 BP 213S EP 213S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700681 ER PT J AU Berman, K AF Berman, Karen TI Translating between genes, brain, and behavior: "Top-Down" and "Bottom-Up" searches for mechanisms in schizophrenia and Williams syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Berman, Karen] NIMH, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 700 BP 222S EP 222S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700710 ER PT J AU Insel, TR AF Insel, Thomas R. TI Mental disorders as developmental brain disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Insel, Thomas R.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 701 BP 222S EP 223S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700711 ER PT J AU Saunders, R AF Saunders, Richard TI The number, type and function of new neurons in the primate frontal cortex SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Saunders, Richard] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 706 BP 224S EP 225S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700716 ER PT J AU Innis, R AF Innis, Robert TI Patients with panic disorder show widespread loss of NK1 receptor binding in brain measured with positron emission tomography SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Innis, Robert] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 710 BP 226S EP 226S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700720 ER PT J AU Savostyanova, AA Stein, JL Tan, HY Goldman, AL Callicott, JH Apudl, JA Meyer-Lindenberg, A Weinberger, DR Marencol, S AF Savostyanova, Antonina A. Stein, Jason L. Tan, Hao Y. Goldman, Aaron L. Callicott, Joseph H. Apudl, Jose A. Meyer-Lindenberg, Andreas Weinberger, Daniel R. Marencol, Stefano TI In vivo assessment of thalamocortical connectivity in schizophrenia using DTI and integrative evidence from fMRI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Savostyanova, Antonina A.; Stein, Jason L.; Tan, Hao Y.; Goldman, Aaron L.; Callicott, Joseph H.; Apudl, Jose A.; Weinberger, Daniel R.; Marencol, Stefano] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-6800 Mannheim, Germany. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 714 BP 227S EP 227S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700724 ER PT J AU Gill, JM Luckenbaugh, D Collin, C Plumb, K West, K Bonne, O Charney, D Vythilingam, M AF Gill, Jessica M. Luckenbaugh, Dave Collin, Carlos Plumb, Katherine West, Kathleen Bonne, Omer Charney, Dennis Vythilingam, Meena TI Comorbid major depression accounts for lower early morning plasma cortisol levels and alterations in plasma dehydroeandosterone sulphate (DHEA-S) in posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Gill, Jessica M.] NINR, NIH, Bethesda, MD 20892 USA. [Luckenbaugh, Dave; Plumb, Katherine; West, Kathleen; Vythilingam, Meena] NIMH, NIH, Bethesda, MD 20892 USA. [Collin, Carlos] Community Behav Hlth, Rockville, MD USA. [Bonne, Omer] Hadassah Med Ctr, Dept Psychiat, IL-91120 Jerusalem, Israel. [Charney, Dennis] Mt Sinai Hosp, Mt Sinai Sch Med, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 718 BP 228S EP 228S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700728 ER PT J AU Gogtay, N AF Gogtay, Nitin TI Gray matter abnormalities in childhood-onset schizophrenia and their full siblings from early childhood to young adulthood SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Gogtay, Nitin] NIMH, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 735 BP 234S EP 234S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700745 ER PT J AU Holmes, A AF Holmes, Andrew TI Genetic factors modulating executive control in the mouse SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Holmes, Andrew] NIAAA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 747 BP 238S EP 238S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700757 ER PT J AU Murray, EBA AF Murray, Elisabeth Betsy A. TI Genetic modulation of cognitive flexibility and socioemotional behavior in rhesus monkeys SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Murray, Elisabeth Betsy A.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 748 BP 238S EP 238S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700758 ER PT J AU Du, J Wang, Y Hunter, R Machado-Vieira, R Wei, YL Falke, C MvEwen, B Manji, H AF Du, Jing Wang, Yun Hunter, Richard Machado-Vieira, Rodrigo Wei, Yanling Falke, Cynthia MvEwen, Bruce Manji, Husseini TI Dynamic regulation of mitochondrial functions by glucocorticoids and stress SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Hunter, Richard; MvEwen, Bruce] Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. [Du, Jing; Wang, Yun; Machado-Vieira, Rodrigo; Wei, Yanling; Falke, Cynthia; Manji, Husseini] NIH, NIMH, Bethesda, MD 20892 USA. RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 760 BP 242S EP 242S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700770 ER PT J AU Li, Z AF Li, Zheng TI Mitochondria in synapse development and plasticity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY MAY 01-03, 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Li, Zheng] NIH, NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 761 BP 242S EP 243S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700771 ER PT J AU Manji, HK AF Manji, Husseini K. TI Bcl-2: A key regulator of affective resilience in the pathophysiology and treatment of severe mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Manji, Husseini K.] NIH, Mood & Anxiety Disorders Program, NIMH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 4 U1 0 U2 2 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 762 BP 243S EP 243S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700772 ER PT J AU Blasi, G Taurisanol, P Papazacharias, A Caforio, G Romano, R Lobianco, L Fazio, L Di Giorgio, A Latorre, V Sambataro, F Nardini, M Mattay, V Weinberger, D Bertolino, A AF Blasi, Giuseppe Taurisanol, Paolo Papazacharias, Apostolos Caforio, Grazia Romano, Raffaella Lobianco, Luciana Fazio, Leonardo Di Giorgio, Annabella Latorre, Valeria Sambataro, Fabio Nardini, Marcello Mattay, Venkata Weinberger, Daniel Bertolino, Alessandro TI Non-linear response of the anterior cingulate and prefrontal cortex in schizophrenia as a function of variable attentional control SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Blasi, Giuseppe; Taurisanol, Paolo; Papazacharias, Apostolos; Caforio, Grazia; Romano, Raffaella; Lobianco, Luciana; Fazio, Leonardo; Di Giorgio, Annabella; Nardini, Marcello; Bertolino, Alessandro] Univ Bari, Dept Neurol & Psychiat Sci, Bari, Italy. [Sambataro, Fabio; Mattay, Venkata; Weinberger, Daniel] NIMH, NIH, Bethesda, MD 20892 USA. RI Fazio, Leonardo/J-4570-2012 OI Fazio, Leonardo/0000-0003-4000-974X NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 782 BP 249S EP 249S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700792 ER PT J AU Eisenberg, DP Sarpal, D Kohn, PD Meyer-Lindenberg, A Wint, D Kolachana, B Weinberger, DR Berman, KF AF Eisenberg, Daniel P. Sarpal, Deepak Kohn, Philip D. Meyer-Lindenberg, Andreas Wint, Dylan Kolachana, Bhaskar Weinberger, Daniel R. Berman, Karen F. TI Disrupted resting functional connectivity between a dorsolateral prefrontal cortex (DLPFC) region showing catechol-O-methyltransferase (COMT) genotype effects and inferior parietal lobule in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Eisenberg, Daniel P.; Sarpal, Deepak; Kohn, Philip D.; Wint, Dylan; Berman, Karen F.] NIMH, Sect Integrat Neuroimaging, Intramural Res Program, NIH,DHHS, Bethesda, MD 20892 USA. [Eisenberg, Daniel P.; Sarpal, Deepak; Kohn, Philip D.; Wint, Dylan; Kolachana, Bhaskar; Weinberger, Daniel R.; Berman, Karen F.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH,DHHS, Bethesda, MD 20892 USA. [Meyer-Lindenberg, Andreas] NIMH, Unit Syst Neurosci Psychiat, Neuroimaging Core Facil, Intramural Res Program,NIH,DHHS, Bethesda, MD 20892 USA. RI Eisenberg, Daniel/C-7432-2014; Sarpal, Deepak/O-5630-2014; Eisenberg, Daniel/S-4342-2016; Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 794 BP 253S EP 253S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700804 ER PT J AU Gruber, O Henseler, I Tost, H Scherk, H Wobrock, T Rietschel, M Falkai, P AF Gruber, Oliver Henseler, Ilona Tost, Heike Scherk, Harald Wobrock, Thomas Rietschel, Marcella Falkai, Peter TI Working memory dysfunction as phenotypic marker of schizophrenic and bipolar affective psychoses: Common and differential abnormalities in brain activation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Gruber, Oliver; Henseler, Ilona; Scherk, Harald; Wobrock, Thomas; Falkai, Peter] Univ Gottingen, Dept Psychiat & Psychotherapy, D-3400 Gottingen, Germany. [Tost, Heike] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Rietschel, Marcella] Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 799 BP 254S EP 255S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700809 ER PT J AU Roe, KV King, EA Sarpal, DK Bonner-Jackson, A Goldberg, TS Meyer-Lindenberg, A Weinberger, DR Berman, KF AF Roe, Katherine V. King, Eric A. Sarpal, Deepak K. Bonner-Jackson, Aaron Goldberg, Terry S. Meyer-Lindenberg, Andreas Weinberger, Daniel R. Berman, Karen F. TI Frontal-temporal connectivity and cognitive dysfunction in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Roe, Katherine V.; King, Eric A.; Sarpal, Deepak K.; Bonner-Jackson, Aaron; Berman, Karen F.] NIMH, Intramural Res Program, Sect Integrat Neuroimaging, NIH,DHHS, Bethesda, MD 20892 USA. [Roe, Katherine V.; King, Eric A.; Sarpal, Deepak K.; Bonner-Jackson, Aaron; Goldberg, Terry S.; Meyer-Lindenberg, Andreas; Weinberger, Daniel R.; Berman, Karen F.] NIMH, Intramural Res Program, Clin Brain Disorders Branch, NIH,DHHS,Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. RI Sarpal, Deepak/O-5630-2014; Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 827 BP 263S EP 263S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700837 ER PT J AU Kempf, L Nicodemus, KK Kolochana, B Vakkalanka, R Verchinski, B Egan, M Straub, R Mattay, V Callicott, J Weinberger, D Meyer-Lindenberg, A AF Kempf, Lucas Nicodemus, Kristin K. Kolochana, Bhaskar Vakkalanka, Radhakrishna Verchinski, Beth Egan, Michael Straub, Richard Mattay, Venkata Callicott, Joseph Weinberger, Daniel Meyer-Lindenberg, Andreas TI Protective and risk functional diplotypes of PRODH schizophrenia risk gene on 22q11, impact on brain structure, function and clinical risk SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Kempf, Lucas; Nicodemus, Kristin K.; Kolochana, Bhaskar; Vakkalanka, Radhakrishna; Verchinski, Beth; Straub, Richard; Mattay, Venkata; Callicott, Joseph; Weinberger, Daniel] NIMH, USNP GCAP, Bethesda, MD USA. [Egan, Michael] Merck & Co Inc, West Point, PA USA. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, Dept Director, D-6800 Mannheim, Germany. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 852 BP 271S EP 271S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700862 ER PT J AU Tan, HY Nicodemus, KK Chen, Q Li, Z Brooke, JK Honea, R Kolachana, BS Straub, RE Sei, Y Meyer-Lindenberg, A Mattay, VS Callicott, JH Weinberger, DR AF Tan, Hao-Yang Nicodemus, Kristin K. Chen, Qiang Li, Zhen Brooke, Jennifer K. Honea, Robyn Kolachana, Bhaskar S. Straub, Richard E. Sei, Yoshitasu Meyer-Lindenberg, Andreas Mattay, Venkata S. Callicott, Joseph H. Weinberger, Daniel R. TI AKT1 influences human prefrontal cortical structure and dopaminergic function SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Tan, Hao-Yang; Nicodemus, Kristin K.; Chen, Qiang; Li, Zhen; Brooke, Jennifer K.; Honea, Robyn; Kolachana, Bhaskar S.; Straub, Richard E.; Sei, Yoshitasu; Meyer-Lindenberg, Andreas; Mattay, Venkata S.; Callicott, Joseph H.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-6800 Mannheim, Germany. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 858 BP 273S EP 273S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700868 ER PT J AU Stern, AJ Zhang, Y Salvadore, G Savostyanova, AS Apud, JA Shen, J Weinberger, DR Marenco, S AF Stern, Alexa J. Zhang, Yan Salvadore, Giacomo Savostyanova, Antonina S. Apud, Jose A. Shen, Jun Weinberger, Daniel R. Marenco, Stefano TI Glutamate in the medial prefrontal cortex of chronic, medicated patients with schizophrenia and healthy comparison subjects assessed with proton MR spectroscopy at 3 tesla SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Stern, Alexa J.; Savostyanova, Antonina S.; Apud, Jose A.; Weinberger, Daniel R.; Marenco, Stefano] NIMH, Clin Brain Disorders Branch, GCAP, Bethesda, MD 20892 USA. [Zhang, Yan; Salvadore, Giacomo; Shen, Jun] NIMH, Mood & Anxiety Disorders Prog, Bethesda, MD 20892 USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 876 BP 278S EP 278S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700886 ER PT J AU Jabbi, M Kema, IP Korf, J Ormel, J den Boer, JA AF Jabbi, Mbemba Kema, Ido P. Korf, Jacob Ormel, Johan den Boer, Johan A. TI Chronic life stress experience and polymorphic variations of MAOA-VNTR and the intron 2-VNTR of the 5-HTT genes modulates endocrine stress response SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY MAY 01-03, 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Jabbi, Mbemba] NIMH, NIH, Cognit Brain Disorders Branch, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. [Kema, Ido P.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Lab Med, NL-9713 AV Groningen, Netherlands. [Korf, Jacob; Ormel, Johan; den Boer, Johan A.] UMCG, Dept Psychiat, Groningen, Netherlands. RI Ormel, Johan/C-6094-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR 1 PY 2008 VL 63 IS 7 SU S MA 944 BP 299S EP 299S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700953 ER PT J AU Cameron, HA Dayer, AG AF Cameron, Heather A. Dayer, Alexandre G. TI New Interneurons in the adult neocortex: Small, sparse, but significant? SO BIOLOGICAL PSYCHIATRY LA English DT Review DE interneurons; neocortex; neurogenesis; non-human primates; rodents ID MEDIAL PREFRONTAL CORTEX; LOCAL-CIRCUIT NEURONS; CELL-PROLIFERATION; PROGENITOR CELLS; DENTATE GYRUS; GABAERGIC INTERNEURONS; CORTICAL NEUROGENESIS; CEREBRAL-CORTEX; STEM-CELLS; IN-VIVO AB During the last decade, the intense study of adult hippocampal neurogenesis has led to several new lines of inquiry in the field of psychiatry. Although it is generally believed that adult mammalian neurogenesis is restricted to the hippocampus and olfactory bulb, a growing number of studies have described new neurons in the adult neocortex in both rodents and nonhuman primates. Interestingly, all of the new neurons observed in these studies have features of interneurons rather than pyramidal cells, the largest neuronal population of the neocortex. In this review, we discuss features of these interneurons that may explain why cortical neurogenesis has been so difficult to detect. In addition, these features suggest ways that production of even a small numbers of new neurons in the adult cortex could make a significant impact on neocortical function. C1 [Cameron, Heather A.] NIMH, Unit Neuroplast, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Dayer, Alexandre G.] Ctr Med Univ Geneva, Dept Adult Psychiat, Geneva, Switzerland. RP Cameron, HA (reprint author), NIMH, Unit Neuroplast, Mood & Anxiety Disorders Program, NIH, Bldg 35-3c915 MSC 3718,35 Lincoln Dr, Bethesda, MD 20892 USA. EM heathercameron@mail.nih.gov RI Cameron, Heather/E-6221-2011; OI Cameron, Heather/0000-0002-3245-5777; Dayer, Alexandre/0000-0002-4490-9780 FU Intramural NIH HHS [Z01 MH002784-06]; NIMH NIH HHS [Z01 MH002784] NR 60 TC 54 Z9 55 U1 0 U2 6 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 APR 1 PY 2008 VL 63 IS 7 BP 650 EP 655 DI 10.1016/j.biopsych.2007.09.023 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 275YB UT WOS:000254107100003 PM 18067877 ER PT J AU Voss, JG Raju, R Logun, C Danner, RL Munson, PJ Rangel, Z Dalakas, MC AF Voss, Joachim G. Raju, Raghavan Logun, Carolea Danner, Robert L. Munson, Peter J. Rangel, Zoila Dalakas, Marinos C. TI A focused microarray to study human mitochondrial and nuclear gene expression SO BIOLOGICAL RESEARCH FOR NURSING LA English DT Article DE mitochondria; microarray; gene expression; interferon gamma ID INTERFERON; METABOLISM; CELLS AB A focused microarray (huMITOchip) was developed to study alterations of human mitochondrial and nuclear gene expression in health and disease. The huMITOchip contains 4,774 probe sets identical to the Affymetrix U 133 plus 2.0 chip covering genes affecting mitochondrial, lipid, cvtokine, apoptosis, and muscle function transcripts. Unlike other gene chips, the huMITOchip has 51 probe sets that interrogate 37 genes of the mitochondrial genome. The human mitochondrial gene chip was validated against the Affymetrix U133 plus 2.0 array using an in vitro system of CCL136 muscle cell line stimulated with or without interferon gamma (IFN-gamma). The 37 genes from the mtDNA demonstrated absolute gene expression levels ranging from 0.1 to 3,182. The comparison of the two gene chips yielded an excellent Pearson's correlation coefficient (r = 0.98). At least 17 probe sets were differentially expressed in response to IFN-gamma on both chips, with a high degree of concordance. This is the first report on the development of a focused oligonucleotide microarray containing genes of the mitochondrial genome. C1 [Voss, Joachim G.; Raju, Raghavan; Dalakas, Marinos C.] NINDS, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. [Logun, Carolea; Danner, Robert L.] Ctr Clin, Funct Genom & Proteom Facil, Dept Crit Care Med, Seattle, WA USA. [Munson, Peter J.; Rangel, Zoila] Ctr Informat Technol, Math & Stat Comp Lab, NIH, Seattle, WA USA. RP Voss, JG (reprint author), Univ Washington, Sch Nursing, Biobehav Nursing & Hlth Syst Dept, Box 357266,Room T 624B, Seattle, WA 98195 USA. EM vossj@u.washington.edu RI Raju, Raghavan/E-9219-2011 FU Intramural NIH HHS [Z01 CT000266-09]; NINR NIH HHS [K22 NR008672] NR 17 TC 9 Z9 9 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1099-8004 J9 BIOL RES NURS JI Biol. Res. Nurs. PD APR PY 2008 VL 9 IS 4 BP 272 EP 279 DI 10.1177/1099800408315160 PG 8 WC Nursing SC Nursing GA 273JM UT WOS:000253926200003 PM 18398222 ER PT J AU Mulkidjanian, AY Galperin, MY Makarova, KS Wolf, YI Koonin, EV AF Mulkidjanian, Armen Y. Galperin, Michael Y. Makarova, Kira S. Wolf, Yuri I. Koonin, Eugene V. TI Evolutionary primacy of sodium bioenergetics SO BIOLOGY DIRECT LA English DT Review ID PROTON-PUMPING ATPASES; VACUOLAR H+-ATPASE; ESCHERICHIA-COLI; LIPID-BILAYERS; V-ATPASE; THERMUS-THERMOPHILUS; ROTARY MOTOR; NA+-ATPASE; F-TYPE; MOLECULAR PHYLOGENETICS AB Background: The F- and V-type ATPases are rotary molecular machines that couple translocation of protons or sodium ions across the membrane to the synthesis or hydrolysis of ATP. Both the F- type (found in most bacteria and eukaryotic mitochondria and chloroplasts) and V-type (found in archaea, some bacteria, and eukaryotic vacuoles) ATPases can translocate either protons or sodium ions. The prevalent proton-dependent ATPases are generally viewed as the primary form of the enzyme whereas the sodium-translocating ATPases of some prokaryotes are usually construed as an exotic adaptation to survival in extreme environments. Results: We combine structural and phylogenetic analyses to clarify the evolutionary relation between the proton- and sodium-translocating ATPases. A comparison of the structures of the membrane-embedded oligomeric proteolipid rings of sodium-dependent F- and V-ATPases reveals nearly identical sets of amino acids involved in sodium binding. We show that the sodium-dependent ATPases are scattered among proton- dependent ATPases in both the F- and the V-branches of the phylogenetic tree. Conclusion: Barring convergent emergence of the same set of ligands in several lineages, these findings indicate that the use of sodium gradient for ATP synthesis is the ancestral modality of membrane bioenergetics. Thus, a primitive, sodium-impermeable but proton- permeable cell membrane that harboured a set of sodium-transporting enzymes appears to have been the evolutionary predecessor of the more structurally demanding proton- tight membranes. The use of proton as the coupling ion appears to be a later innovation that emerged on several independent occasions. Reviewers: This article was reviewed by J. Peter Gogarten, Martijn A. Huynen, and Igor B. Zhulin. For the full reviews, please go to the Reviewers' comments section. C1 [Galperin, Michael Y.; Makarova, Kira S.; Wolf, Yuri I.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Mulkidjanian, Armen Y.] Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. [Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119991, Russia. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM amulkid@uos.de; galperin@ncbi.nlm.nih.gov; makarova@ncbi.nlm.nih.gov; wolf@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013; Mulkidjanian, Armen/J-8086-2013 OI Galperin, Michael/0000-0002-2265-5572; Mulkidjanian, Armen/0000-0001-5844-3064 FU Intramural NIH HHS [Z99 LM999999] NR 108 TC 69 Z9 72 U1 0 U2 17 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 APR 1 PY 2008 VL 3 AR 13 DI 10.1186/1745-6150-3-13 PG 19 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 303KM UT WOS:000256039400001 PM 18380897 ER PT J AU Chu, YW Gress, RE AF Chu, Yu-Waye Gress, Ronald E. TI Murine models of chronic graft-versus-host disease: Insights and unresolved issues SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE murine models; graft-versus-host disease; allogeneic hematopoietic stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; CD4(+) T-CELLS; MINOR HISTOCOMPATIBILITY BARRIERS; IDIOPATHIC PNEUMONIA SYNDROME; IDENTICAL SIBLING DONORS; ANTIGEN-PRESENTING CELLS; CLINICAL-TRIALS AB Chronic graft-versus-host-disease (cGVHD) is a major barrier to successful allogeneic hematopoietic stein cell transplantation (allo-HSCT), with highly variable clinical presentations. The pathophysiology of cGVHD remains relatively poorly understood. The utilization of murine models to study cGVHD encompasses experimental challenges distinct from those that have been successfully used to study acute GVHD (aGVHD). Nevertheless, despite these challenges, murine models of cGVHD have contributed to the understanding of cGVHD, and highlight its mechanistic complexity. In this article, insights into the pathophysiology of cGVHD obtained from murine studies are summarized in the context of their relevancy to clinical cGVHD. Despite experimental limitations, current and future models of murine cGVHD will continue to provide insights into the understanding of clinical cGVHD and provide information for new therapeutic interventions. (c) 2008 American Society for Blood and Marrow Transplantation C1 [Chu, Yu-Waye; Gress, Ronald E.] NIH, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Chu, YW (reprint author), NIH, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bldg 10,CRC Rm 3-3288,10 Ctr Dr, Bethesda, MD 20892 USA. EM chuy@mail.nih.gov FU Intramural NIH HHS [NIH0010820025]; PHS HHS [NIH0010820025] NR 117 TC 78 Z9 86 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2008 VL 14 IS 4 BP 365 EP 378 DI 10.1016/j.bbmt.2007.12.002 PG 14 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 280IC UT WOS:000254418500001 PM 18342778 ER PT J AU Russo, AL Citrin, D Camphausen, K AF Russo, Andrea L. Citrin, Deborab Camphausen, Kevin TI Biomarkers in radiation oncology SO BIOMARKERS IN MEDICINE LA English DT Review DE biomarker; immunohistochemistry; MMP-2; Rad51; radiation; urine; VEGF ID ENDOTHELIAL GROWTH-FACTOR; FACTOR PROTEIN-LEVELS; CELL LUNG-CANCER; IONIZING-RADIATION; MATRIX METALLOPROTEINASES; HOMOLOGOUS RECOMBINATION; PROGNOSTIC-SIGNIFICANCE; RAD51 PROTEIN; THERAPY; EXPRESSION AB The discovery of biomarkers in patients receiving radiation therapy for cancer is occurring at an exceptional pace. There are a number of ways to conduct biomarker investigations, although the majority of clinically relevant biomarker studies have used immunohistochemistry (IHC) on tissue specimens. Using IHC, expression of several preradiation biomarkers, such as VEGF, EGFR, YKL-40, murine double minute 2 and Rad51, has been associated with a poor outcome. Because tumor tissue may be difficult to obtain and IHC studies can be difficult to reproduce and standardize, investigators have attempted to find similar results when studying biomarkers of nontumor biospecimens, such as serum and urine. This has led to the discovery of a number of soluble biomarkers predictive of outcome (e.g., YKL-40, VEGF and matrix metallopepticlase-2). As we transition from the use of biopsy-based markers to surrogate soluble biomarkers in the hope of bringing these biomarkers into clinical use, we must ensure methods of standardization in sample collection, processing, storage and analysis to allow widespread reproducibility and accuracy of results. C1 [Russo, Andrea L.; Citrin, Deborab; Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Russo, Andrea L.] Howard Hughes Med Inst, NIH, Bethesda, MD 20817 USA. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, 10 Ctr Dr 3B42, Bethesda, MD 20892 USA. EM camphauk@mail.nih.gov FU National Institutes of Health, National Cancer Institute FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. NR 36 TC 2 Z9 2 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD APR PY 2008 VL 2 IS 2 BP 155 EP 163 DI 10.2217/17520363.2.2.155 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 344IY UT WOS:000258921300012 PM 20477437 ER PT J AU Moncada, V Srivastava, S AF Moncada, Victoria Srivastava, Sudhir TI Biomarkers in oncology research and treatment: early detection research network: a collaborative approach SO BIOMARKERS IN MEDICINE LA English DT Article DE biomarker; genomics; overfitting; proteomics; sensitivity; specificity; validation ID PROSTATE-CANCER CELLS; METASTATIC BREAST-CANCER; GENE-EXPRESSION; OVARIAN-CANCER; BLADDER-CANCER; MICROSATELLITE ANALYSIS; MONOCLONAL-ANTIBODY; MOLECULAR-DETECTION; PROTEOMIC ANALYSIS; COLORECTAL-CANCER AB Several important criteria are essential for the development of biomarkers in clinical oncology. First, the biomarkers should be easily measured using standardized and cost-efficient methods. Second, biomarkers should be easily attainable from clinical materials such as body fluids and cells. Third, biomarkers should have clearly defined cutoff values with high sensitivity and specificity. Lastly, the predictive value of biomarkers should be possible in strata as large as possible. Single biomarkers may not be able to meet all of these criteria, which necessitates the development of biomarker panels. High-throughput technologies will be necessary for measuring these biomarker sets and translation of these methods into a clinical setting will be necessary in order to employ these biomarkers in a healthcare setting. One of the most important aspects of biomarker development will be standardization and statistical evaluation of biomarker studies. Guidelines for biomarker studies need to be developed that will enable standardization to take place. The Early Detection Research Network has been in the forefront of this objective. Early detection of cancer through appropriately validated biomarkers will provide for decreased morbidity and mortality and allow for the development of new therapeutic tools targeted specifically toward eradication of these early malignancies, hopefully increasing the survival rate of patients diagnosed with early-stage cancer. C1 [Moncada, Victoria; Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Srivastava, S (reprint author), NCI, Canc Biomarkers Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. EM vmoncada@mail.nih.gov; ssla@nih.gov NR 55 TC 5 Z9 5 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD APR PY 2008 VL 2 IS 2 BP 181 EP 195 DI 10.2217/17520363.2.2,181 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 344IY UT WOS:000258921300014 PM 20477439 ER PT J AU Bencherif, SA Srinivasan, A Horkay, F Hollinger, JO Matyjaszewski, K Washburn, NR AF Bencherif, Sidi A. Srinivasan, Abiraman Horkay, Ferenc Hollinger, Jeffrey O. Matyjaszewski, Krzysztof Washburn, Newell R. TI Influence of the degree of methacrylation on hyaluronic acid hydrogels properties SO BIOMATERIALS LA English DT Article DE hyaluronic acid; cross-linking; hydrogels; mechanical properties; cell response ID IDENTIFICATION; NETWORKS; ADHESION; DOMAINS AB The properties of hyaluronic acid (HA) hydrogels having a broad range of methacrylation are presented. Increasing solubility of glycidyl methacrylate (GM) in a co-solvent mixture during the methacrylation of HA with GM was shown to produce photopolymerizable HAGM conjugates with various degree of methacrylation (DM) ranging from 14% up to 90%. Aqueous solutions of HAGM macromonomers were photocross-linked to yield hydrogels with nearly full vinyl group conversions after 10 min exposure under ultraviolet light (UV). Hydrogels were characterized by uniaxial compression and volumetric swelling measurements. Keeping the DM constant, the shear modulus was varied from 16 kPa up to 73 kPa by varying the macromonomer concentration. However, at a given macromonomer concentration while varying the DM, similarly the shear modulus varied from 22 kPa up to 65 kPa. Preliminary in-vitro cell culture studies showed that GRGDS modified HAGM hydrogels promoted similarly cell interaction at both low and high DMs, 32% and 60%, respectively. Densely cross-linked hydrogels with a high DM have been shown to be more mechanically robust while maintaining cytocompability and cell adhesion. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Bencherif, Sidi A.; Matyjaszewski, Krzysztof; Washburn, Newell R.] Carnegie Mellon Univ, Dept Chem, Pittsburgh, PA 15213 USA. [Srinivasan, Abiraman; Hollinger, Jeffrey O.] Carnegie Mellon Univ, Bone Tissue Engn Ctr, Pittsburgh, PA 15213 USA. [Horkay, Ferenc] NICHD, Sect Tissue Biphys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. [Washburn, Newell R.] Carnegie Mellon Univ, Dept Biomed Engn, Pittsburgh, PA 15213 USA. RP Washburn, NR (reprint author), Carnegie Mellon Univ, Dept Chem, 4400 5th Ave, Pittsburgh, PA 15213 USA. EM washburn@andrew.cmu.edu RI ATRP, ATRP/A-3613-2009; Matyjaszewski, Krzysztof/A-2508-2008; OI Matyjaszewski, Krzysztof/0000-0003-1960-3402; BENCHERIF, SIDI/0000-0002-7704-5608 FU Intramural NIH HHS; NIDCR NIH HHS [R01 DE 15392-4] NR 26 TC 77 Z9 81 U1 8 U2 55 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD APR PY 2008 VL 29 IS 12 BP 1739 EP 1749 DI 10.1016/j.biomaterials.2007.11.047 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 284TV UT WOS:000254729800002 PM 18234331 ER PT J AU Maurois, P Rocchi, S Pages, N Bac, P Stables, JP Gressens, P Vamecq, J AF Maurois, Pierre Rocchi, Stephane Pages, Nicole Bac, Pierre Stables, James P. Gressens, Pierre Vamecq, Joseph TI The PPAR gamma agonist FMOC-L-leucine protects both mature and immature brain SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE immature brain; neuroprotection; injury; anticonvulsant; FMOC-L-leucine; PPAR gamma ID PROLIFERATOR-ACTIVATED RECEPTORS; MAGNESIUM-DEFICIENCY; MOUSE MODEL; CELL-DEATH; NEUROPROTECTION; APOPTOSIS; WHITE; MICE AB (N-[9-fluorenylmethoxycarbonyl]-)-L-leucine (FMOC-L-leucine) and rosiglitazone, two ligands of peroxisome proliferator-activated receptor gamma (PPAR gamma), were evaluated in mature (adult mice) and immature (pups) brain injury models. In adult magnesium-deficient mice, a model responsive to both neuroprotective and anti-seizure compounds, FMOC-L-leucine, but not rosiglitazone, protected against audiogenic seizures. The protection afforded by FMOC-L-leucine was alleviated by the PPAR gamma antagonist GW9662 (1-2 mg/kg) and was induced in 50% animals by 4.8 +/- 1.2 mg/kg. At this dose, FMOC-L-leucine modified audiogenic seizure phase durations in convulsing mice differently than prototype antiepileptic drugs did. FMOC-L-leucine (up to 100 mg/kg) was inactive in the 6 Hz seizure test, an adult animal model largely responsive to anti-seizure drugs. In a model of neonatal brain injury, FMOC-L-leucine (4 mu g/kg) was neuroprotective against cerebral ibotenate toxicity. It reduced significantly the size of lesions in grey but not in white matter, while rosiglitazone (10 mu g/kg) was inactive. Taken as a whole, the present data support neuroprotective potentialities of FMOC-L-leucine towards both mature and immature brain. The PPAR-based protection of immature brain is more important as it is known that classic adult brain protectants (GABA(A) activators, N-methyl-D-aspartate and sodium channel blockers) may be toxic for immature brain. The PPAR gamma agonist FMOC-L-leucine is likely to be devoid of these classic protective mechanisms because of its inactivity in the 6 Hz seizure test, its activity in the audiogenic test being explained by neuroprotective rather than intrinsic anti-seizure mechanisms. Targeting PPARs might be thus a promising way to protect immature brain. (c) 2007 Elsevier Masson SAS. All rights reserved. C1 [Maurois, Pierre; Bac, Pierre] Ctr Chirurg Marie Lannelongue, CNRS, UMR 8162, F-92350 Le Plessis Robinson, France. [Maurois, Pierre; Bac, Pierre] Univ Paris 11, Fac Pharm, F-92296 Chatenay Malabry, France. [Rocchi, Stephane] Fac Med, INSERM, U597, F-06107 Nice, France. [Pages, Nicole] Univ Strasbourg 1, Fac Pharm, F-67401 Illkirch Graffenstaden, France. [Stables, James P.] NINDS, Epilepsy Branch, NIH, Ctr Neurosci, Bethesda, MD 20892 USA. [Gressens, Pierre] Hop Robert Debre, INSERM, U676, F-75019 Paris, France. [Gressens, Pierre] Univ Paris 07, Fac Med Denis Diderot, IFR02, F-75018 Paris, France. [Gressens, Pierre] Univ Paris 07, Fac Med Denis Diderot, IFR25, F-75018 Paris, France. [Vamecq, Joseph] Univ Lille 2, Fac Med, INSERM, EA1046,Univ 045131, F-59045 Lille, France. RP Vamecq, J (reprint author), Univ Lille 2, Fac Med, INSERM, EA1046,Univ 045131, 1 Place Verdun, F-59045 Lille, France. EM vamecq@lille.inserm.fr RI Rocchi, Stephane/O-4152-2016; OI Rocchi, Stephane/0000-0002-0943-1304; Gressens, Pierre/0000-0002-0909-4221 NR 20 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD APR-MAY PY 2008 VL 62 IS 4 BP 259 EP 263 DI 10.1016/j.biopha.2007.10.014 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 310CK UT WOS:000256506300009 PM 18343627 ER PT J AU Chen, XW Li, ZH AF Chen, Xiaowu Li, Zhaohai TI Inference of haplotype effects in case-control studies using unphased genotype and environmental data SO BIOMETRICAL JOURNAL LA English DT Article DE haplotype; case-control; ECM; environmental covariate ID MAXIMUM-LIKELIHOOD-ESTIMATION; UNRELATED INDIVIDUALS; ASSOCIATION ANALYSIS; CONTINUOUS TRAITS; LINKAGE PHASE; POPULATION; ALGORITHM; GENETICS; FREQUENCIES; DISCRETE AB retrospective likelihood-based approach was proposed to test and estimate the effect of haplotype on disease risk using unphased genotype data with adjustment for environmental covariates. The proposed method was also extended to handle the data in which the haplotype and environmental covariates are not independent. Likelihood ratio tests were constructed to test the effects of haplotype and gene-environment interaction. The model parameters such as haplotype effect size was estimated using an Expectation Conditional-Maximization (ECM) algorithm developed by Meng and Rubin (1993). Model-based variance estimates were derived using the observed information matrix. Simulation studies were conducted for three different genetic effect models, including dominant effect, recessive effect, and additive effect. The results showed that the proposed method generated unbiased parameter estimates, proper type I error, and true P coverage probabilities. The model performed well with small or large sample sizes, as well as short or long haplotypes. C1 [Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Chen, Xiaowu] Human Genome Sci Inc, Dept Biostat, Rockville, MD USA. [Li, Zhaohai] NICHHD, Dept Hlth & Human Serv, Biometry & Math Stat Branch, Rockville, MD 20852 USA. RP Li, ZH (reprint author), George Washington Univ, Dept Stat, 2140 Pennsylvania Ave, Washington, DC 20052 USA. EM zli@gwu.edu FU NEI NIH HHS [EY014478] NR 27 TC 2 Z9 2 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD APR PY 2008 VL 50 IS 2 BP 270 EP 282 DI 10.1002/bimj.200710396 PG 13 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 292JQ UT WOS:000255262700010 PM 18217697 ER PT J AU Das, U Das, S Bandy, B Stables, JP Dimmock, JR AF Das, Umashankar Das, Swagatika Bandy, Brian Stables, James P. Dimmock, Jonathan R. TI N-Aroyl-3,5-bis(benzylidene)-4-piperidones: A novel class of antimycobacterial agents SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE 3,5-bis(benzylidene)-4-piperidones; antimycobacterial; neurotoxic; mitochondria; rodent toxicity; piperidones; antitubercular ID RAT-LIVER MITOCHONDRIA; MANNICH-BASES; ANTITUBERCULOSIS AGENTS; CYTOTOXIC PROPERTIES; KETONES; DERIVATIVES; HYDROCHLORIDE; TUBERCULOSIS; RESPIRATION; DESIGN AB A number of 3,5-bis(benzylidene)-4-piperidones 1 and some N-4-(2-aminoethoxy) phenylcarbonyl analogs 3-6 display excellent in vitro antimycobacterial properties. In particular, 1c and 6d are potent antimycobacterials which are well tolerated in mice and are identified as important lead molecules. The nature of both the benzylidene aryl rings and the terminal basic groups which affect the antimycobacterial potencies and the absence of neurotoxic side effects were identified. Several representative compounds stimulated respiration in mitochondria isolated from rat liver and this effect was not caused by the swelling of these organelles. Various guidelines for the creation of further related novel antimycobacterial agents are provided. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Das, Umashankar; Das, Swagatika; Bandy, Brian; Dimmock, Jonathan R.] Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. [Stables, James P.] NINDS, Rockville, MD 20852 USA. RP Dimmock, JR (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. EM jr.dimmock@usask.ca FU Canadian Institutes of Health Research [53171] NR 33 TC 35 Z9 38 U1 1 U2 3 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 APR 1 PY 2008 VL 16 IS 7 BP 3602 EP 3607 DI 10.1016/j.bmc.2008.02.009 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 292DE UT WOS:000255245900013 PM 18282710 ER PT J AU Li, XJ Manjunatha, UH Goodwin, MB Knox, JE Lipinski, CA Keller, TH Barry, CE Dowd, CS AF Li, Xiaojin Manjunatha, Ujjini H. Goodwin, Michael B. Knox, John E. Lipinski, Christopher A. Keller, Thomas H. Barry, Clifton E., III Dowd, Cynthia S. TI Synthesis and antitubercular activity of 7-(R)- and 7-(S)-methyl-2-nitro-6-(S)-(4-(trifluoromethoxy)benzyloxy)6,7-dihydro-5H -imidazo[2,1-b][1,3]oxazines, analogues of PA-824 SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Mycobacterium tuberculosis; PA-824; solubility; water solubility ID MYCOBACTERIUM-TUBERCULOSIS; NITROIMIDAZOPYRAN PA-824; RESISTANCE; PROSPECTS; SERIES AB Nitroimidazoles such as PA-824 and OPC-67683 are currently in clinical development as members of a promising new class of therapeutics for tuberculosis. While the antitubercular activity of these compounds is high, they both suffer from poor water solubility thus complicating development. We determined the single crystal X-ray structure of PA-824 and found a close packing of the nitroimidazoles facilitated by a pseudoaxial conformation of the p-trifluoromethoxybenzyl ether. To attempt to disrupt this tight packing by destabilizing the axial preference of this side chain, we prepared the two diastereomers of the 7-methyl-nitroimidazo-oxazine. Determination of the crystal structure of the 7-(R)-methyl derivative (5, cis) revealed that the benzylic side chain remained pseudoaxial while the 7-(R)-methyl derivative (6, trans) adopted the desired pseudoequatorial conformation. Both derivatives displayed similar activities against Mycobacterium tuberculosis, but neither showed improved aqueous solubility, suggesting that inherent lattice stability is not likely to be a major factor in limiting solubility. Conformational analysis revealed that all three compounds have similar energetically accessible conformations in solution. Additionally, these results suggest that the nitroreductase that initially recognizes PA-824 is somewhat insensitive to substitutions at the 7-position. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Li, Xiaojin; Manjunatha, Ujjini H.; Goodwin, Michael B.; Barry, Clifton E., III; Dowd, Cynthia S.] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA. [Knox, John E.; Keller, Thomas H.] Novartis Inst Trop Dis, Singapore 138670, Singapore. [Lipinski, Christopher A.] Melior Discovery, Waterford, CT 06385 USA. RP Dowd, CS (reprint author), George Washington Univ, Dept Chem, 725 21st St NW,Corcoran Hall 107, Washington, DC 20052 USA. EM cdowd@gwu.edu RI Barry, III, Clifton/H-3839-2012; OI Lipinski, Christopher/0000-0001-7355-7254; Keller, Thomas/0000-0002-7553-6235 FU Intramural NIH HHS [Z01 AI000693-15] NR 20 TC 37 Z9 38 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 1 PY 2008 VL 18 IS 7 BP 2256 EP 2262 DI 10.1016/j.bmcl.2008.03.011 PG 7 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 292DI UT WOS:000255246300003 PM 18358721 ER PT J AU Stanley, C Krueger, S Parsegian, VA Rau, DC AF Stanley, Christopher Krueger, Susan Parsegian, V. Adrian Rau, Donald C. TI Protein structure and hydration probed by SANS and osmotic stress SO BIOPHYSICAL JOURNAL LA English DT Article ID ANGLE NEUTRON-SCATTERING; PREFERENTIAL HYDRATION; GUANYLATE KINASE; SUBSTRATE-BINDING; WATER; EXCLUSION; DNA; STABILITY; POLYMERS; FORCES AB Interactions governing protein folding, stability, recognition, and activity are mediated by hydration. Here, we use small-angle neutron scattering coupled with osmotic stress to investigate the hydration of two proteins, lysozyme and guanylate kinase (GK), in the presence of solutes. By taking advantage of the neutron contrast variation that occurs upon addition of these solutes, the number of protein-associated (solute-excluded) water molecules can be estimated from changes in both the zero-angle scattering intensity and the radius of gyration. Poly(ethylene glycol) exclusion varies with molecular weight. This sensitivity can be exploited to probe structural features such as the large internal GK cavity. For GK, small-angle neutron scattering is complemented by isothermal titration calorimetry with osmotic stress to also measure hydration changes accompanying ligand binding. These results provide a framework for studying other biomolecular systems and assemblies using neutron scattering together with osmotic stress. C1 [Stanley, Christopher; Krueger, Susan] Natl Inst Stand & Technol, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Stanley, Christopher; Parsegian, V. Adrian; Rau, Donald C.] NICHHD, Lab Phys & Struct Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Stanley, C (reprint author), Oak Ridge Natl Lab, Neutron Scattering Sci Div, Oak Ridge, TN 37831 USA. EM stanleycb@ornl.gov OI Stanley, Christopher/0000-0002-4226-7710 FU Intramural NIH HHS NR 50 TC 16 Z9 16 U1 2 U2 19 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR 1 PY 2008 VL 94 IS 7 BP 2777 EP 2789 DI 10.1529/biophysj.107.122697 PG 13 WC Biophysics SC Biophysics GA 275MM UT WOS:000254076300034 PM 18178651 ER PT J AU Ozarslan, E Nevo, U Basser, PJ AF Ozarslan, Evren Nevo, Uri Basser, Peter J. TI Anisotropy induced by macroscopic boundaries: Surface-normal mapping using diffusion-weighted imaging SO BIOPHYSICAL JOURNAL LA English DT Article ID ATTENUATED MR SIGNAL; HUMAN CEREBRAL-CORTEX; EDGE ENHANCEMENT; RESTRICTED DIFFUSION; WATER DIFFUSION; FIELD-GRADIENT; RADIAL ORGANIZATION; TENSOR MRI; NMR; BRAIN AB In MRI, macroscopic boundaries lead to a diffusion-related increase in signal intensity near them-an effect commonly referred to as edge-enhancement. In diffusion-weighted imaging protocols where the signal attenuation due to diffusion results predominantly from the application of magnetic field gradients, edge-enhancement will depend on the orientation of these diffusion gradients. The resulting diffusion anisotropy can be exploited to map the direction normal to the macroscopic boundary. Simulations suggest that the hypothesized anisotropy may be within observable limits even when the voxel contains no boundary itself-hence, the name remote-an isotropy. Moreover, for certain experimental parameters there may be significant phase cancellations within the voxel that may lead to an edge detraction effect. When this is avoided, the eigenvector corresponding to the smallest eigenvalue of the diffusion tensor obtained from diffusion-tensor imaging can be used to create surface-normal maps conveniently. Experiments performed on simple geometric constructs as well as real tissue demonstrate the feasibility of using the edge-enhancement mechanism to map orientations orthogonal to macroscopic surfaces, which may be used to assess the integrity of tissue and organ boundaries noninvasively. C1 [Ozarslan, Evren; Nevo, Uri; Basser, Peter J.] NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Ozarslan, E (reprint author), NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. EM evren@helix.nih.gov RI Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011 OI Ozarslan, Evren/0000-0003-0859-1311; FU Intramural NIH HHS NR 44 TC 15 Z9 15 U1 1 U2 4 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR 1 PY 2008 VL 94 IS 7 BP 2809 EP 2818 DI 10.1529/biophysj.107.124081 PG 10 WC Biophysics SC Biophysics GA 275MM UT WOS:000254076300037 PM 18065457 ER PT J AU Minton, AP AF Minton, Allen P. TI Effective hard particle model for the osmotic pressure of highly concentrated binary protein solutions SO BIOPHYSICAL JOURNAL LA English DT Article ID BOVINE SERUM-ALBUMIN; SEDIMENTATION EQUILIBRIUM; LIGHT-SCATTERING; SYSTEMS; NUMBER AB The experimentally measured concentration dependence of the osmotic pressure of an equimolar mixture of hen egg ovalbumin and bovine serum albumin at pH 7.0 and 25 degrees C in the presence of 0.15 M NaCl is shown to be quantitatively accounted for by a model in which each protein species is represented by an effective hard sphere. The size of this sphere is determined by analysis of the concentration dependence of the osmotic pressure of the isolated protein. C1 NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Minton, AP (reprint author), NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM minton@helix.nih.gov OI Minton, Allen/0000-0001-8459-1247 FU Intramural NIH HHS NR 19 TC 19 Z9 19 U1 0 U2 9 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR 1 PY 2008 VL 94 IS 7 BP L57 EP L59 DI 10.1529/biophysj.107.128033 PG 3 WC Biophysics SC Biophysics GA 275MM UT WOS:000254076300005 PM 18212007 ER PT J AU Vaiana, SM Ghirlando, R Yau, WM Eaton, WA Hofrichter, J AF Vaiana, Sara M. Ghirlando, Rodolfo Yau, Wai-Ming Eaton, William A. Hofrichter, James TI Sedimentation studies on human amylin fail to detect low-molecular-weight oligomers SO BIOPHYSICAL JOURNAL LA English DT Article ID ISLET AMYLOID POLYPEPTIDE; TYPE-2 DIABETES-MELLITUS; COMMON MECHANISM; FIBRILS; PROTEIN; CYTOTOXICITY; AGGREGATION; TOXICITY; PEPTIDE; DISEASE AB Sedimentation velocity experiments show that only monomers coexist with amyloid fibrils of human islet amyloid-polypeptide. No oligomers containing < 100 monomers could be detected, suggesting that the putative toxic oligomers are much larger than those found for the Alzheimer's peptide, A beta(1-42). C1 [Vaiana, Sara M.; Yau, Wai-Ming; Eaton, William A.; Hofrichter, James] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD USA. RP Hofrichter, J (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM jameshof@niddk.nih.gov RI Ghirlando, Rodolfo/A-8880-2009 FU Intramural NIH HHS NR 27 TC 26 Z9 26 U1 1 U2 6 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR 1 PY 2008 VL 94 IS 7 BP L45 EP L47 DI 10.1529/biophysj.107.125146 PG 3 WC Biophysics SC Biophysics GA 275MM UT WOS:000254076300001 PM 18223003 ER PT J AU Gail, MH Pfeiffer, RM Wheeler, W Pee, D AF Gail, Mitchell H. Pfeiffer, Ruth M. Wheeler, William Pee, David TI Probability of detecting disease-associated single nucleotide polymorphisms in case-control genome-wide association studies SO BIOSTATISTICS LA English DT Article DE case-control study; detection probability; genetic association; genome-wide association study; ranking and selection; whole genome scan ID SAMPLE-SIZE; GENOTYPES; FALSE AB Some case-control genome-wide association studies (CCGWASs) select promising single nucleotide polymorphisms (SNPs) by ranking corresponding p-values, rather than by applying the same p-value threshold to each SNP. For such a study, we define the detection probability (DP) for a specific disease-associated SNP as the probability that the SNP will be "T-selected," namely have one of the top T largest chi-square values (or smallest p-values) for trend tests of association. The corresponding proportion positive (PP) is the fraction of selected SNPs that are true disease-associated SNPs. We study DP and PP analytically and via simulations, both for fixed and for random effects models of genetic risk, that allow for heterogeneity in genetic risk. DP increases with genetic effect size and case-control sample size and decreases with the number of nondisease-associated SNPs, mainly through the ratio of T to N, the total number of SNPs. We show that DP increases very slowly with T, and the increment in DP per unit increase in T declines rapidly with T. DP is also diminished if the number of true disease SNPs exceeds T. For a genetic odds ratio per minor disease allele of 1.2 or less, even a CCGWAS with 1000 cases and 1000 controls requires T to be impractically large to achieve an acceptable DP, leading to PP values so low as to make the study futile and misleading. We further calculate the sample size of the initial CCGWAS that is required to minimize the total cost of a research program that also includes follow-up studies to examine the T-selected SNPs. A large initial CCGWAS is desirable if genetic effects are small or if the cost of a follow-up study is large. C1 [Gail, Mitchell H.; Pfeiffer, Ruth M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wheeler, William; Pee, David] Informat Management Serv Inc, Rockville, MD USA. RP Gail, MH (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8032, Bethesda, MD 20892 USA. EM gailm@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 FU Intramural NIH HHS NR 16 TC 27 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2008 VL 9 IS 2 BP 201 EP 215 DI 10.1093/biostatistics/kxm032 PG 15 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 278NK UT WOS:000254293400001 PM 17873152 ER PT J AU Zhou, M Veenstra, TD AF Zhou, Ming Veenstra, Timothy D. TI Mass spectrometry: m/z 1983-2008 SO BIOTECHNIQUES LA English DT Review ID PEPTIDE AB While definitely not a new technology, mass spectrometry (MS) has seen incredible growth over the past 25 Years. Mass spectrometry has rapidly evolved to the forefront of analytical techniques; its ability to analyze proteins is the major driving force in the field of proteomics, MS instrumentation has increased approximately 5-fold in sensitivity every three years. The level of performance that is achievable with MS today allows scientists to study proteins in ways that were inconceivable a quarter century ago. This review of the history of MS over the past 25 years is timely in that it encompasses two of the biggest developments, electrospray and matrix-assisted laser desorption/ionization (MALDI), which have enabled many of the uses of this technology today. C1 [Zhou, Ming; Veenstra, Timothy D.] NCI, SAIC Frederick Inc, Adv Technol Program, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), NCI, SAIC Frederick Inc, Adv Technol Program, Lab Proteom & Analyt Technol, POB B, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov FU National Cancer Institute, National Institutes of Health [NO1-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. NO1-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 mention of trade names, commercial products, or organizations imply endorsement by the United States Government. NR 13 TC 24 Z9 32 U1 1 U2 9 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD APR PY 2008 VL 44 IS 5 BP 667 EP + DI 10.2144/000112791 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 411GP UT WOS:000263637600013 PM 18474043 ER PT J AU Issaq, HJ Veenstra, TD AF Issaq, Haleem J. Veenstra, Timothy D. TI Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE): advances and perspectives SO BIOTECHNIQUES LA English DT Review ID IMMOBILIZED PH GRADIENTS; PLASMA-PROTEINS; SERUM-PROTEINS; RESOLUTION; PROTEOMICS AB The recent trend in science is to assay as many biological molecules as possible within a single experiment. This trend is evident in proteomics where the aim is to characterize thousands of proteins within cells, tissues, and organisms. While advances in mass spectrometry have been critical, developments made in two-dimensional PAGE (2D-PAGE) have also played a major role in enabling proteomics. In this review. we discuss and highlight the advances made in 2D-PAGE over the past 25 years that have made it a foundational tool in proteomic research. C1 [Issaq, Haleem J.; Veenstra, Timothy D.] NCI, SAIC Frederick Inc, Adv Technol Program, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, SAIC Frederick Inc, Adv Technol Program, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. EM issaqh@ncifcrf.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400] FX The project has been funded in whole or 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 mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 15 TC 94 Z9 100 U1 4 U2 35 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD APR PY 2008 VL 44 IS 5 BP 697 EP + DI 10.2144/000112823 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 411GP UT WOS:000263637600017 PM 18474047 ER PT J AU Singh, AK Kruecker, J Xu, S Glossop, N Guion, P Ullman, K Choyke, PL Wood, BJ AF Singh, Anurag K. Kruecker, Jochen Xu, Sheng Glossop, Neil Guion, Peter Ullman, Karen Choyke, Peter L. Wood, Bradford J. TI Initial clinical experience with real-time transrectal ultrasonography-magnetic resonance imaging fusion-guided prostate biopsy SO BJU INTERNATIONAL LA English DT Article DE magnetic resonance; ultrasound; prostate cancer; imaging; transrectal ID INTENSITY FOCUSED ULTRASOUND; RADICAL PROSTATECTOMY; TUMOR FOCI; CANCER; MEN; SPECTROSCOPY; ABLATION; THERAPY; MRI AB OBJECTIVE To evaluate the feasibility and utility of registration and fusion of real-time transrectal ultrasonography (TRUS) and previously acquired magnetic resonance imaging (MRI) to guide prostate biopsies. PATIENTS AND METHODS Two National Cancer Institute trials allowed MRI-guided (with or with no US fusion) prostate biopsies during placement of fiducial markers. Fiducial markers were used to guide patient set-up for daily external beam radiation therapy. The eligible patients had biopsy-confirmed prostate cancer that was visible on MRI. A high-field (3T) MRI was performed with an endorectal coil in place. After moving to an US suite, the patient then underwent TRUS to visualize the prostate. The US transducer was equipped with a commercial needle guide and custom modified with two embedded miniature orthogonal five-degrees of freedom sensors to enable spatial tracking and registration with MR images in six degrees of freedom. The MRI sequence of choice was registered manually to the US using custom software for real-time navigation and feedback. The interface displayed the actual and projected needle pathways superimposed upon the real-time US blended with the prior MR images, with position data updating in real time at 10 frames per second. The registered MRI information blended to the real-time US was available to the physician who performed targeted biopsies of highly suspicious areas. RESULTS Five patients underwent limited focal biopsy and fiducial marker placement with real-time TRUS-MRI fusion. The Gleason scores at the time of enrolment on study were 8, 7, 9, 9, and 6. Of the 11 targeted biopsies, eight showed prostate cancer. Positive biopsies were found in all patients. The entire TRUS procedure, with fusion, took approximate to 10 min. CONCLUSION The fusion of real-time TRUS and prior MR images of the prostate is feasible and enables MRI-guided interventions (like prostate biopsy) outside of the MRI suite. The technique allows for navigation within dynamic contrast-enhanced maps, or T2-weighted or MR spectroscopy images. This technique is a rapid way to facilitate MRI-guided prostate therapies such as external beam radiation therapy, brachytherapy, cryoablation, high-intensity focused ultrasound ablation, or direct injection of agents, without the cost, throughput, or equipment compatibility issues that might arise with MRI-guided interventions inside the MRI suite. C1 [Singh, Anurag K.] Roswell Pk Canc Inst, Dept Radiat Med, Buffalo, NY 14263 USA. [Kruecker, Jochen; Xu, Sheng] Philips Res N Amer, Briarcliff Manor, NY USA. [Guion, Peter; Ullman, Karen] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Choyke, Peter L.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Wood, Bradford J.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Glossop, Neil] Traxtal Technol Inc, Toronto, ON, Canada. RP Singh, AK (reprint author), Roswell Pk Canc Inst, Dept Radiat Med, Elm & Carlton St, Buffalo, NY 14263 USA. EM anurag.singh@roswellpark.org FU Intramural NIH HHS [Z99 CL999999] NR 19 TC 107 Z9 118 U1 2 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD APR PY 2008 VL 101 IS 7 BP 841 EP 845 DI 10.1111/j.1464-410X.2007.07348.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 270ZB UT WOS:000253757600013 PM 18070196 ER PT J AU Li, HQ Raia, V Bertolini, F Price, DK Figg, WD AF Li, Haiqing Raia, Valentina Bertolini, Francesco Price, Douglas K. Figg, William D. TI Circulating endothelial cells as a therapeutic marker for thalidomide in combined therapy with chemotherapy drugs in a human prostate cancer model SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; angiogenesis; thalidomide; endothelial cells; docetaxel ID PHASE-II TRIAL; BREAST-CANCER; ANGIOGENESIS; INHIBITOR; DOCETAXEL; CARCINOMA; VIABILITY; SURVIVAL; KINETICS; DISEASE AB To investigate how thalidomide confers its survival benefit in prostate cancer, by assessing its effect on circulating endothelial cells (CECs) and progenitors (CEPs) in a combined therapy of thalidomide and chemotherapy drugs in a human prostate cancer xenograft model, as in clinical trials patients treated with both thalidomide and docetaxel had a > 50% decrease in prostate-specific antigen (PSA) levels and longer median overall survival than those treated with docetaxel monotherapy. A human prostate cancer xenograft model was used to evaluate the effect of either thalidomide, docetaxel or a combination of the two drugs on circulating ECs. Drug treatment was continued for 17 days, and tumours were measured two or three times a week. Blood samples were taken at three different time points: before the treatments, 4 days and 17 days into the treatments, and CECs and CEPs were measured by flow cytometry analysis. There was an increased level of apoptotic/dead CECs shortly after the intravenous injection of docetaxel, and the addition of thalidomide further increased the apoptotic/dead CEC level, showing that thalidomide enhances the cytotoxicity of docetaxel against tumour vascular ECs. Thalidomide increased the apoptotic/dead CEC level and enhanced the cytotoxicity of docetaxel against tumour vascular ECs, confirming its antiangiogenic property in vivo in combined anticancer treatments. In addition, there was a correlation between the increased apoptotic/dead CEC levels early in the treatment and antitumour efficacy later, suggesting that the apoptotic/dead CEC level could be used as a marker, at an early stage, to predict tumour response to antiangiogenic therapies. C1 [Li, Haiqing; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Raia, Valentina; Bertolini, Francesco] European Inst Oncol, Dept Med, Div Hematol Oncol, Milan, Italy. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bldg 10,Room 5AO1,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Raia, Valentina/E-8845-2010; Figg Sr, William/M-2411-2016 NR 26 TC 21 Z9 23 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD APR PY 2008 VL 101 IS 7 BP 884 EP 888 DI 10.1111/j.1464-410X.2007.07342.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 270ZB UT WOS:000253757600020 PM 18070197 ER PT J AU Scortegagna, M Cataisson, C Martin, RJ Hicklin, DJ Schreiber, RD Yuspa, SH Arbeit, JM AF Scortegagna, Marzia Cataisson, Christophe Martin, Rebecca J. Hicklin, Daniel J. Schreiber, Robert D. Yuspa, Stuart H. Arbeit, Jeffrey M. TI HIF-1 alpha regulates epithelial inflammation by cell autonomous NF kappa B activation and paracrine stromal remodeling SO BLOOD LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1; TYPE-16 TRANSGENIC MICE; TUMOR-NECROSIS-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; INTRAEPIDERMAL INFLAMMATION; GROWTH-FACTOR; CANCER CELLS; FACTOR-ALPHA; EXPRESSION; KINASE AB Hypoxia inducible factor-1 (HIF-1) is a master regulatory transcription factor controlling multiple cell-autonomous and non-cell-autonomous processes, such as metabolism, angiogenesis, matrix invasion, and cancer metastasis. Here we used a new line of transgenic mice with constitutive gain of HIF-1 function in basal keratinocytes and demonstrated a signaling pathway from HIF-1 to nuclear factor kappa B (NF kappa B) activation to enhanced epithelial chemokine and cytokine elaboration. This pathway was responsible for a phenotypically silent accumulation of stromal inflammatory cells and a marked in-flammatory hypersensitivity to a single 12-O-tetradecanoylphorbol-13-acetate (TPA) challenge. HIF-1-induced NF kappa B activation was composed of 2 elements, I kappa B hyperphosphorylation and phosphorylation of Ser276 on p65, enhancing p65 nuclear localization and transcriptional activity, respectively. NF kappa B transcriptional targets macrophage inflammatory protein-2 (MIP-2/CXCL2/3), keratinocyte chemokine (KC/CXCL1), and tumor necrosis factor [alfa] (TNF alpha) were constitutively up-regulated and further increased after TPA challenge both in cultured keratinocytes and in transgenic mice. Whole animal KC, MIP-2, or TNF alpha immunodepletion each abrogated TPA-induced inflammation, whereas blockade of either VEGF or placenta growth factor (PIGF) signaling did not affect transgenic inflammatory hyper-responsiveness. Thus, epithelial HIF-1 gain of function remodels the local environment by cell-autonomous NF kappa B-mediated chemokine and cytokine secretion, which may be another mechanism by which HIF-1 facilitates either inflammatory diseases or malignant progression. C1 [Scortegagna, Marzia; Martin, Rebecca J.; Arbeit, Jeffrey M.] Washington Univ, Sch Med, Dept Surg, Div Urol, St Louis, MO 63110 USA. [Cataisson, Christophe; Yuspa, Stuart H.] NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Hicklin, Daniel J.] ImClone Syst, New York, NY USA. [Schreiber, Robert D.] Washington Univ, Sch Med, Ctr Immunol, Dept Pathol & Immunol, St Louis, MO USA. [Schreiber, Robert D.; Arbeit, Jeffrey M.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [Arbeit, Jeffrey M.] Washington Univ, Sch Med, Cell Biol Program, Div Biol & Biomed Sci, St Louis, MO USA. RP Arbeit, JM (reprint author), Washington Univ, Sch Med, Dept Surg Urol & Cell Biol, 660 S Euclid,Campus Box 8242, St Louis, MO 63110 USA. EM arbeitj@msnotes.wustl.edu RI Schreiber, Robert/A-1276-2013 OI Schreiber, Robert/0000-0001-6311-0432 FU NCI NIH HHS [R01 CA090722, R01-CA90722] NR 49 TC 69 Z9 74 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 APR 1 PY 2008 VL 111 IS 7 BP 3343 EP 3354 DI 10.1182/blood-2007-10-115758 PG 12 WC Hematology SC Hematology GA 282LM UT WOS:000254569300016 PM 18199827 ER PT J AU Brown, LM Gridley, G Check, D Landgren, O AF Brown, Linda Morris Gridley, Gloria Check, David Landgren, Ola TI Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders SO BLOOD LA English DT Article ID CHRONIC ANTIGENIC-STIMULATION; RHEUMATOID-ARTHRITIS; ANKYLOSING-SPONDYLITIS; MEDICAL CONDITIONS; PERNICIOUS-ANEMIA; CANCER; COHORT; GLOMERULONEPHRITIS; HEPATITIS; DIAGNOSIS AB In a retrospective cohort of more than 4 million white and black male United States (US) veterans, we explored the role of specific prior autoimmune, infectious, inflammatory, and allergic disorders in the etiology of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Patients were selected from computerized inpatient discharge records at US Veterans Affairs hospitals. The analysis included 4641 patients (3040 white, 1601 black) and 2046 patients (1312 white; 734 black) with a discharge diagnosis of MM and MGUS, respectively. Using Poisson regression, we calculated age-adjusted relative risks (RRs) and 95% confidence intervals (Cls) for the relationship between MM, MGUS, and specific prior medical conditions. Significantly elevated risks of MM were associated with broad categories of autoimmune (RR, 1.15; 95% Cl, 1.02-1.28), infectious (RR, 1.29; 95% Cl, 1.20-1.38), and inflammatory disorders (RR, 1.18; 95% Cl, 1.10-1.27) and specific prior autoimmune (polymyositis/dermatomyositis, systemic sclerosis, autoimmune hemolytic anemia, pernicious anemia, and ankylosing spondylitis), infectious (pneumonia, hepatitis, meningitis, septicemia, herpes zoster, and poliomyelitis), and inflammatory (glomerulonephritis, nephrotic syndrome, and osteoarthritis) disorders. Risks for MGUS were generally of similar magnitude. Our results indicate that various types of immune-mediated conditions might act as triggers for MM/MGUS development. C1 [Brown, Linda Morris] RTI Int, Rockville, MD 20852 USA. [Brown, Linda Morris; Gridley, Gloria; Check, David; Landgren, Ola] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Sci, Bethesda, MD 20892 USA. RP Brown, LM (reprint author), RTI Int, 6110 Execut Blvd,Suite 902, Rockville, MD 20852 USA. EM lindabrown@rti.org RI Check, David/J-7184-2015 OI Check, David/0000-0003-3887-0493 FU Intramural NIH HHS NR 53 TC 102 Z9 105 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 APR 1 PY 2008 VL 111 IS 7 BP 3388 EP 3394 DI 10.1182/blood-2007-10-121285 PG 7 WC Hematology SC Hematology GA 282LM UT WOS:000254569300022 PM 18239085 ER PT J AU Li, X Stankovic, M Bonder, CS Hahn, CN Parsons, M Pitson, SM Xia, P Proia, RL Vadas, MA Gamble, JR AF Li, Xiaochun Stankovic, Milena Bonder, Claudine S. Hahn, Christopher N. Parsons, Michelle Pitson, Stuart M. Xia, Pu Proia, Richard L. Vadas, Mathew A. Gamble, Jennifer R. TI Basal and angiopoietin-1-mediated endothelial permeability is regulated by sphingosine kinase-1 SO BLOOD LA English DT Article ID SIGNALING PATHWAY; BARRIER INTEGRITY; TIE2 RECEPTOR; ACTIVATION; PROTEIN; CELLS; 1-PHOSPHATE; PHOSPHORYLATION; MIGRATION; SPHINGOSINE-1-PHOSPHATE AB Endothelial cells (ECs) regulate the barrier function of blood vessels. Here we show that basal and angiopoietin-1 (Ang-1)-regulated control of EC permeability is mediated by 2 different functional states of sphingosine kinase-1 (SK-1). Mice depleted of SK-1 have increased vascular leakiness, whereas mice transgenic for SK-1 in ECs show attenuation of leakiness. Furthermore, Ang-1 rapidly and transiently stimulates SK-1 activity and phosphorylation, and induces an increase in intracellular sphingosine-1-phosphate (S1P) concentration. Overexpression of SK-1 resulted in inhibition of permeability similar to that seen for Ang-1, whereas knockdown of SK-1 by small interfering RNA blocked Ang-1-mediated inhibition of permeability. Transfection with SKS225A, a nonphosphorylatable mutant of SK-1, inhibited basal leakiness, and both SKS225A and a dominant-negative SK-1 mutant removed the capacity of Ang-1 to inhibit permeability. These effects were indepen-dent of extracellular S1P as knockdown or inhibition of S1P(1), S1P(2), or S1P(3), did not affect the Ang-1 response. Thus, SK-1 levels in ECs powerfully regulate basal permeability in vitro and in vivo. In addition, the Ang-1-induced inhibition of leakiness is mediated through activation of SK-1, defining a new signaling pathway in the Ang-1 regulation of permeability. C1 [Li, Xiaochun; Stankovic, Milena; Bonder, Claudine S.; Hahn, Christopher N.; Parsons, Michelle; Pitson, Stuart M.] Inst Med & Vet Sci, Hanson Inst, Div Human Immunol, Adelaide, SA, Australia. [Xia, Pu; Vadas, Mathew A.; Gamble, Jennifer R.] Univ Sydney, Centenary Inst Canc Med & Cell Biol, Med Fdn, Sydney, NSW, Australia. [Proia, Richard L.] NIDDK, Natl Inst Hlth, Genet Dev & Dis Branch, Bethesda, MD USA. RP Gamble, JR (reprint author), Centenary Inst Canc Med & Cell Biol, Locked Bag 6, Newtown, NSW 2042, Australia. EM j.gamble@centenary.org.au RI Xia, Pu/G-3090-2010; Proia, Richard/A-7908-2012; Hahn, Christopher/C-1369-2009 OI Xia, Pu/0000-0003-4705-8878; Hahn, Christopher/0000-0001-5105-2554 NR 37 TC 48 Z9 49 U1 0 U2 4 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 APR 1 PY 2008 VL 111 IS 7 BP 3489 EP 3497 DI 10.1182/blood-2007-05-092148 PG 9 WC Hematology SC Hematology GA 282LM UT WOS:000254569300035 PM 18199826 ER PT J AU Choi, EY Orlova, VV Fagerholm, SC Nurmi, SM Zhang, L Ballantyne, CM Gahmberg, CG Chavakis, T AF Choi, Eun Young Orlova, Valeria V. Fagerholm, Susanna C. Nurmi, Susanna M. Zhang, Li Ballantyne, Christie M. Gahmberg, Carl G. Chavakis, Triantafyllos TI Regulation of LFA-1-dependent inflammatory cell recruitment by Cb1-b and 14-3-3 proteins SO BLOOD LA English DT Article ID EXTRACELLULAR ADHERENCE PROTEIN; CBL ADAPTER PROTEIN; C-CBL; NEGATIVE REGULATION; CYTOPLASMIC DOMAIN; INTEGRIN PHOSPHORYLATION; STAPHYLOCOCCUS-AUREUS; EFFECTOR MOLECULE; UBIQUITIN LIGASES; HUMAN NEUTROPHILS AB Inside-out signaling regulation of the beta 2-integrin leukocyte function-associated antigen-1 (LFA-1) by different cytoplasmic proteins, including 14-3-3 proteins, is essential for adhesion and migration of immune cells. Here, we identify a new pathway for the regulation of LFA-1 activity by Cbl-b, an adapter molecule and ubiquitin ligase that modulates several signaling pathways. Cbl-b-1- mice displayed increased macrophage recruitment in thioglycollate-induced peritonitis, which was attributed to CbI-b deficiency in macrophages, as assessed by bone marrow chimera experiments. In vitro, Cbl-b(-1-) bone marrow-derived mononuclear phagocytes (BMDMs) displayed increased adhesion to endothelial cells. Activation of LFA-1 in Cbl-b-deficient cells was responsible for their increased endothelial adhesion in vitro and peritoneal recruitment in vivo, as the phenotype of Cbl-b deficiency was reversed in Cbl-b(-/-)LFA-1 (-/-) mice. Consistently, LFA-1-mediated adhesion of BMDM to ICAM-1 but not VLA-4-mediated adhesion to VCAM-1 was enhanced by CbI-b deficiency. Cbl-b deficiency resulted in increased phosphorylation of T758 in the beta 2-chain of LFA-1 and thereby in enhanced association of 14-3-30 protein with the beta 2-chain, leading to activation of LFA-1. Consistently, disruption of the 14-3-3/beta 2-integrin interaction abrogated the enhanced ICAM-1 adhesion of Cbl-b-1- BMDMs. In conclusion, CbI-b deficiency activates LFA-1 and LFA-1-mediated inflammatory cell recruitment by stimulating the interaction between the LFA-1 beta-chain and 14-3-3 proteins. C1 [Choi, Eun Young; Orlova, Valeria V.; Chavakis, Triantafyllos] NCI, NIH, EIB, Bethesda, MD 20892 USA. [Fagerholm, Susanna C.; Nurmi, Susanna M.; Gahmberg, Carl G.] Univ Helsinki, Fac Biosci, Div Biochem, FIN-00014 Helsinki, Finland. [Fagerholm, Susanna C.] Univ Dundee, Sch Med, Dundee DD1 4HN, Scotland. [Fagerholm, Susanna C.] Ninewells Hosp, Div Pathol & Nuerosci, Dundee, Scotland. [Zhang, Li] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Ballantyne, Christie M.] Methodist DeBakey Heart Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. RP Chavakis, T (reprint author), NCI, NIH, EIB, 10 Ctr Dr,Rm 4B17, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov RI Orlova, Valeria/C-6065-2014; OI Orlova, Valeria/0000-0002-1169-2802; Gahmberg, Carl/0000-0001-9892-9296; Fagerholm, Susanna Carola/0000-0002-0354-8763 FU Intramural NIH HHS; NHLBI NIH HHS [P01 HL054710, R01 HL061589] NR 41 TC 32 Z9 33 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD APR 1 PY 2008 VL 111 IS 7 BP 3607 EP 3614 DI 10.1182/blood-2007-07-103077 PG 8 WC Hematology SC Hematology GA 282LM UT WOS:000254569300049 PM 18239087 ER PT J AU Tiwari, N Wang, CC Brochetta, C Ke, G Vita, F Qi, Z Rivera, J Soranzo, MR Zabucchi, G Hong, WJ Blank, U AF Tiwari, Neeraj Wang, Cheng-Chun Brochetta, Cristiana Ke, Gou Vita, Francesca Qi, Zeng Rivera, Juan Soranzo, Maria Rosa Zabucchi, Giuliano Hong, Wanjin Blank, Ulrich TI VAWP-8 segregates mast cell-preformed mediator exocytosis from cytokine trafficking pathways SO BLOOD LA English DT Article ID FC-EPSILON-RI; SECRETORY GRANULES; TNF-ALPHA; REGULATED EXOCYTOSIS; DEGRANULATION; SNARE; IGE; EFFECTOR; RELEASE; LYSOSOMES AB Inflammatory responses by mast cells are characterized by massive exocytosis of prestored granular mediators followed by cytokine/chemokine release. The vesicular trafficking mechanisms involved remain poorly understood. Vesicular-associated membrane protein-8 (VAMP-8), a member of the soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor (SNARE) family of fusion proteins initially characterized in endosomal and endosomal-lysosomal fusion, may also function in regulated exocytosis. Here we show that in bone marrow-derived mast cells (BMMCs) VAMP-8 partially colocalized with secretory granules and redistributed upon stimulation. This was associated with increased SNARE complex formation with the target t-SNAREs, SNAP-23 and syntaxin-4. VAMP-8-deficient BMMCs exhibited a markedly reduced degranulation response after IgE(+) antigen-, thapsigargin-, or ionomycin-induced stimulation. VAMP-8-deficient mice also showed reduced plasma histamine levels in passive systemic anaphylaxis experiments, while cytokine/chemokine release was not affected. Unprocessed TNF accumulated at the plasma membrane where it colocalized with a VAMP-3-positive vesicular compartment but not with VAMP-8. The findings demonstrate that VAMP-8 segregates secretory lysosomal granule exocytosis in mast cells from cytokine/chemokine molecular trafficking pathways. C1 [Tiwari, Neeraj; Brochetta, Cristiana; Blank, Ulrich] Univ Paris 07, Fac Med, INSERM, U Immunopathol Renale Recepteurs & Inflammat 699, F-75870 Paris, France. [Tiwari, Neeraj; Brochetta, Cristiana; Blank, Ulrich] INSERM, U699, Paris, France. [Wang, Cheng-Chun; Ke, Gou; Qi, Zeng; Hong, Wanjin] Inst Mol & Cellular Biol, Membrane Biol Lab, Proteos, Singapore. [Vita, Francesca; Soranzo, Maria Rosa; Zabucchi, Giuliano] Univ Trieste, Dept Physiol & Pathol, Trieste, Italy. [Rivera, Juan] NIAMSD, Lab Immune Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Blank, U (reprint author), Univ Paris 07, Fac Med, INSERM, U Immunopathol Renale Recepteurs & Inflammat 699, Site Xavier Bichat,16 Rue Henri Huchard,BP416, F-75870 Paris, France. EM ublank@bichat.inserm.fr RI HONG, Wanjin/E-9927-2010; ASTAR, IMCB/E-2320-2012; Tiwari, Neeraj/F-7489-2014 OI Tiwari, Neeraj/0000-0003-3911-4809 FU Intramural NIH HHS NR 47 TC 83 Z9 85 U1 0 U2 5 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 APR 1 PY 2008 VL 111 IS 7 BP 3665 EP 3674 DI 10.1182/blood-2007-07-103309 PG 10 WC Hematology SC Hematology GA 282LM UT WOS:000254569300055 PM 18203950 ER PT J AU Feng, XM Kajigaya, S Solomou, EE Keyvanfar, K Xu, XL Raghavachari, N Munson, PJ Herndon, TM Chen, JC Young, NS AF Feng, Xingmin Kajigaya, Sachiko Solomou, Elena E. Keyvanfar, Keyvan Xu, Xiuli Raghavachari, Nalini Munson, Peter J. Herndon, Thomas M. Chen, Jichun Young, Neal S. TI Rabbit ATG but not horse ATG promotes expansion of functional CD4(+)CD25(high)FOXP3(+) regulatory T cells in vitro SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; ADULT RENAL-TRANSPLANTATION; ANTI-THYMOCYTE GLOBULIN; ANTITHYMOCYTE GLOBULIN; APLASTIC-ANEMIA; SUPPRESSIVE ACTIVITY; TRANSCRIPTION FACTOR; GENE-EXPRESSION; TUMOR-IMMUNITY; INDUCTION AB Regulatory T cells (Treg) play important roles in suppressing immune responses and maintaining tolerance. Rabbit antithymocyte globulin (rATG) and horse ATG (hATG) are widely used in the treatment of immune-mediated syndromes, but their effects on Treg are unknown. We show here that in vitro culture of normal human peripheral blood mononuclear cells (PBMCs) with a low-dose rATG resulted in marked expansion of functional Treg by converting CD4(+)CD25(-) T cells to CD4(+)CD25(+) T cells. hATG did not expand but rather decreased Treg. Immunoblot showed increased expression of FOXP3 and NFAT1 in CD4(+)CD25(-) and CD4(+)CD25(+) T cells exposed to rATG. PBMCs treated with rATG displayed increased interleukin-10 in culture supernatants than those treated with hATG. Furthermore, rATG and hATG showed differences in their potential to stimulate CD4(+) T cells as examined using different activation markers. Microarray revealed that rATG induced markedly different gene-expression patterns in PBMCs, compared with hATG-treated or untreated PBMCs. Our findings indicate that rATG expanded Treg, probably through transcriptional regulation by enhanced NFAT1 expression, in turn conferring CD4(+)CD25(-) T cell FOXP3 expression and regulatory activity. The therapeutic effects of rATG may occur not only because of lymphocyte depletion but also enhanced Treg cell number and function. C1 [Feng, Xingmin; Kajigaya, Sachiko; Solomou, Elena E.; Keyvanfar, Keyvan; Herndon, Thomas M.; Chen, Jichun; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Xu, Xiuli; Raghavachari, Nalini] NHLBI, Genom Core Facil, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Munson, Peter J.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Feng, XM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10-CRC,Rm 3E-5216,9000 Rockville Pike, Bethesda, MD 20892 USA. EM fengx2@nhlbi.nih.gov FU Intramural NIH HHS NR 47 TC 125 Z9 133 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 APR 1 PY 2008 VL 111 IS 7 BP 3675 EP 3683 DI 10.1182/blood-2008-01-130146 PG 9 WC Hematology SC Hematology GA 282LM UT WOS:000254569300056 PM 18250226 ER PT J AU Lam, LT Wright, G Davis, RE Lenz, G Farinha, P Dang, L Chan, JW Rosenwald, A Gascoyne, RD Staudt, LM AF Lam, Lloyd T. Wright, George Davis, R. Eric Lenz, Georg Farinha, Pedro Dang, Lenny Chan, John W. Rosenwald, Andreas Gascoyne, Randy D. Staudt, Louis M. TI Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-kappa B pathways in subtypes of diffuse large B-cell lymphoma SO BLOOD LA English DT Article ID BH3 MIMETIC ABT-737; GENE-EXPRESSION; IN-VIVO; CANCER; STAT3; INHIBITOR; APOPTOSIS; PROTEINS; FAMILY; DIFFERENTIATION AB The activated B cell-like (ABC) subgroup of diffuse large B-cell lymphoma (DLBCL) is characterized by constitutive activation of the nuclear factor-kappa B (NF-kappa B) pathway. In this study, we showed that the NF-kappa B pathway induced the expression of the cytokines interleukin (IL)-6 and IL-1 0 in ABC DLBCL cell lines, which also have high levels of total and phosphorylated signal transducer and activator of transcription (STAT) 3 protein, suggesting autocrine signaling. Using RNA interference for STAT3, we defined a gene expression signature of IL-6 and IL-10 signaling through STAT3. Based on this signature, we constructed a molecular predictor of STAT3 signaling that defined a subset of ABC DLBCL tumors with high expression of STAT3, IL-6, and/or IL-10 and their downstream targets. Although the STAT3-high and STAT3-low subsets had equivalent expression of genes that distinguish ABC DLBCL from germinal center B cell-like DLBCL, STAT3-high ABC DLBCLs had higher expression of signatures that reflected NF-kappa B activity, proliferation, and glycolysis. A small-molecule inhibitor of Janus kinase signaling, which blocked STAT3 signature expression, was toxic only for ABC DLBCL lines and synergized with an inhibitor of NF-kappa B signaling. These findings suggest that the biological interplay between the STAT3 and NF-kappa B pathways may be exploited for the treatments of a subset of ABC DLBCLs. C1 [Lam, Lloyd T.; Davis, R. Eric; Lenz, Georg; Staudt, Louis M.] NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Wright, George] NCI, Biometr Res Branch, Rockville, MD USA. [Farinha, Pedro; Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Dang, Lenny] Millennium Pharmaceut Inc, Cambridge, MA USA. [Chan, John W.] Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE USA. [Chan, John W.] Univ Nebraska Med Ctr, Dept Microbiol, Omaha, NE USA. [Rosenwald, Andreas] Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. RP Staudt, LM (reprint author), 9000 Rockville Pike,Bldg 10,Room 4N114, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov RI Lenz, Georg/I-6844-2012; OI Farinha, Pedro/0000-0001-9364-9391 FU Intramural NIH HHS; NCI NIH HHS [U01 CA084967, U01-CA84967] NR 60 TC 177 Z9 182 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 APR 1 PY 2008 VL 111 IS 7 BP 3701 EP 3713 DI 10.1182/blood-2007-09-111948 PG 13 WC Hematology SC Hematology GA 282LM UT WOS:000254569300059 PM 18160665 ER PT J AU Yin, L Du, X Li, CL Xu, XL Chen, Z Su, N Zhao, L Qi, HB Li, FB Xue, J Yang, J Jin, M Deng, CX Chen, L AF Yin, Liangjun Du, Xiaolan Li, Cuiling Xu, Xiaoling Chen, Zhi Su, Nan Zhao, Ling Qi, Huabing Li, Fubing Xue, Jing Yang, Jing Jin, Min Deng, Chuxia Chen, Lin TI A Pro253Arg mutation in fibroblast growth factor receptor 2 (Fgfr2) causes skeleton malformation mimicking human Apert syndrome by affecting both chondrogenesis and osteogenesis SO BONE LA English DT Article DE fibroblast growth factor receptor 2; Apert syndrome; chondrocyte; osteoblast; mouse model ID PROTEIN-KINASE-C; CRANIAL SUTURE CLOSURE; BONE-DEVELOPMENT; OSTEOBLAST DIFFERENTIATION; SIGNALING PATHWAYS; CELL-DIFFERENTIATION; INCREASED EXPRESSION; PLATE CHONDROCYTES; RNA INTERFERENCE; PREMATURE FUSION AB Apert syndrome is one of the most severe craniosynostosis that is mainly caused by either a Ser252Trp(S252W) or Pro253Arg(P253R) mutation in fibroblast growth factor receptor 2 (FGFR2). As an autosomal dominant disorder, Apert syndrome is mainly characterized by skull malformation resulting from premature fusion of craniofacial sutures, as well as syndactyly, etc. A P253R mutation of FGFR2 results in nearly one-thirds of the cases of Apert syndrome. The pathogenesis of Apert syndrome resulting from P253R mutation of FGFR2 is still not fully understood. Here we reported a knock-in mouse model carrying P253R mutation in Fgfr2. The mutant mice exhibit smaller body size and brachycephaly. Analysis of the mutant skulls and long bones revealed premature fusion of coronal suture, shortened cranial base and growth plates of long bones. In vitro organ culture studies further revealed that, compared with wild-type littermates, the mutant mice have prematurely fused coronal sutures and retarded long bone growth. Treatment of the cultured calvaria and femur with PD98059, an Erk1/2 inhibitor, resulted in partially alleviated coronal suture fusion and growth retardation of femur respectively. Our data indicated that the P253R mutation in Fgfr2 directly affect intramembranous and endochondral ossification, which resulted in the premature closure of coronal sutures and growth retardation of long bones and cranial base. And the Erk1/2 signaling pathway partially mediated the effects of P253R mutation of Fgfr2 on cranial sutures and long bones. (c) 2007 Elsevier Inc. All rights reserved. C1 [Li, Cuiling; Xu, Xiaoling; Deng, Chuxia] NIDDK, NIH, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. [Yin, Liangjun; Du, Xiaolan; Chen, Zhi; Su, Nan; Zhao, Ling; Qi, Huabing; Li, Fubing; Yang, Jing; Jin, Min; Chen, Lin] Third Mil Med Univ, Daping Hosp, Inst Surg Res,Ctr Trauma, State Key Lab Trauma Burns & Combined Injury, Chongqing 400042, Peoples R China. [Xue, Jing] Sichuan Univ, W China Ctr Med Sci, Chengdu 610041, Peoples R China. [Yin, Liangjun] Chongqing Med Univ, Affiliated Hosp 2, Chongqing 400010, Peoples R China. RP Deng, CX (reprint author), NIDDK, NIH, Genet Dev & Dis Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov; linchen70@163.com RI deng, chuxia/N-6713-2016 NR 82 TC 62 Z9 70 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2008 VL 42 IS 4 BP 631 EP 643 DI 10.1016/j.bone.2007.11.019 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 283NQ UT WOS:000254643500004 PM 18242159 ER PT J AU Qiang, YW Barlogie, B Rudikoff, S Shaughnessy, JD AF Qiang, Ya-Wei Barlogie, Bart Rudikoff, Stuart Shaughnessy, John D., Jr. TI Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma SO BONE LA English DT Article DE Wnt; Dkk1; BMP-2; osteoblast; bone disease; myeloma ID RECEPTOR-RELATED PROTEIN-5; BETA-CATENIN; TRANSCRIPTIONAL ACTIVATION; CROSS-TALK; CELLS; DISEASE; EXPRESSION; PATHWAY; MASS; PROLIFERATION AB Expression of the Wnt signaling inhibitor, DKK1 by multiple myeloma cells is correlated with lytic bone disease in multiple myeloma. However, the mechanism(s) by which DKK1 contributes to this process is not clear. Herein, we analyzed the functional role of canonical Wnt signaling and Dkk1 inhibition of this pathway in bone morphogenic protein (BMP)-2-induced osteoblast differentiation. Osteoblast differentiation was measured by alkaline phosphatase (ALP) activity in murine (C2C12) and human pre-osteoblast (hFOB1.19) and osteoblast-like (Saos-2 and MG63) cell lines. Cytoplasmic beta-catcnin protein was separated by E-cadherin-GST pull-down assay and analyzed by Western blotting. A dominant negative form of beta-catenin, Dkk1 and TCF reporter constructs were transfected into C2C12 cells. C2C12 cells were also transfected with siRNA specific to LRP5/6 to knockdown receptor expression. Canonical Wnt signaling was activated in these cell lines in response to Wnt3a, as assessed by increased cytoplasmic, non-phosphorylated beta-catenin and TCF/LEF transcription activity. Recombinant Dkk1 and plasma from MM patients containing high levels of Dkk1 blocked Wnt3a-induced beta-catenin accumulation. Importantly, Dkk1 abrogated BMP-2 mediated osteoblast differentiation. The requirement for Wnt signaling in osteoblast differentiation was confirmed by the following observations: 1) overexpression of Dkk1 decreased endogenous beta-catenin and ALP activity; 2) silencing of Wnt receptor mRNAs blocked ALP activity; and 3) a dominant negative form of beta-catenin eliminated BMP-2-induced ALP activity. Furthermore, Wnt3a did not increase ALP activity nor did BMP-2 treatment result in beta-catenin stabilization indicating that cooperation between these two pathways is required, but they are not co-regulated by either ligand. These studies have revealed that autocrine Wnt signaling in osteoblasts is necessary to promote BMP-2-mediated differentiation of pre-osteoblast cells, while Wnt signaling alone is not capable of inducing such differentiation. Dkk1 inhibits this process and may be a key factor regulating pre-osteoblast differentiation and myeloma bone disease. (c) 2007 Elsevier Inc. All rights reserved. C1 [Qiang, Ya-Wei; Barlogie, Bart; Shaughnessy, John D., Jr.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Rudikoff, Stuart] NCI, NIH, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP Qiang, YW (reprint author), Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. EM yqiang@uams.edu; shaughnessyjohn@uams.edu FU NCI NIH HHS [CA97513] NR 54 TC 89 Z9 101 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2008 VL 42 IS 4 BP 669 EP 680 DI 10.1016/j.bone.2007.12.006 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 283NQ UT WOS:000254643500008 PM 18294945 ER PT J AU Lang, T Koyarna, A Li, C Li, J Lu, Y Saeed, I Gazze, E Keyak, J Harris, T Cheng, X AF Lang, T. Koyarna, A. Li, C. Li, J. Lu, Y. Saeed, I. Gazze, E. Keyak, J. Harris, T. Cheng, X. TI Pelvic body composition measurements by quantitative computed tomography: Association with recent hip fracture SO BONE LA English DT Article DE hip fracture; muscle; computed tomography; osteoporosis ID SINGLE-STEP RECOVERY; BONE-MINERAL DENSITY; LOWER-EXTREMITY PERFORMANCE; LONG-DURATION SPACEFLIGHT; FEMORAL-NECK FRACTURE; SKELETAL-MUSCLE; JOINT TORQUES; GENDER-DIFFERENCES; FAT DISTRIBUTION; PROXIMAL FEMUR AB Introduction: Loss of subcutaneous fat, decreased muscle cross-sectional area (CSA) and increased muscle adiposity are related to declining physical function and disability in the elderly, but there is little information about the relationship of these tissue changes to hip fracture. Thus we have compared body composition measures in women with hip fractures to age-matched controls, using quantitative computed tomography (QCT) imaging of the hip to characterize total adiposity, muscle CSA and muscle attenuation coefficient, a measure of adiposity. Materials and methods: 45 Chinese women (mean age 74.71 +/- 5.94) with hip fractures were compared to 66 healthy control subjects (mean age 70.70 +/- 4.66). Hip QCT scans were analyzed to compute total adipose CSA as well as CSA and attenuation values of muscle groups in the CT scan field of view, including hip extensors, abductors, adductors and flexors. The total femur areal BMD (aBMD) was estimated from the QCT images. Logistic regression was employed to compare body composition measures between fracture subjects and controls after adjustment for age, height, BMI and aBMD. Receiver-operator curve (ROC) analyses determined whether combinations of aBMD and body composition had higher area under curve (AUC) than aBMD alone. Results and conclusions: Fracture subjects had lower fat CSA (p<0.0001) than controls but had higher muscle adiposity as indicated by lower attenuation in the adductor, abductor and flexor groups (0.00001 T, -502 G > T and -385 C > A) were significantly associated with the fetal haemoglobin (HbF) response in Hb SS patients treated with HC (P < 0.05). In addition, four SNPs (rs2310991, -809 C > T, -385 C > A and rs4282891) were significantly associated with the change in absolute HbF after 2 years of treatment with HC. These data suggest that variation within SAR1A regulatory elements might contribute to inter-individual differences in regulation of HbF expression and patient responses to HC in SCD. C1 [Kumkhaek, Chutima; Zhu, Jianqiong; Rodgers, Griffin P.] NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. [Taylor, James G.; Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Hoppe, Carolyn] Childrens Hosp & Res Ctr Oakland, Dept Hematol Oncol, Oakland, CA USA. [Kato, Gregory J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Rodgers, GP (reprint author), NIDDKD, Mol & Clin Hematol Branch, NIH, 10 Ctr Dr,Rm 9N115, Bethesda, MD 20892 USA. EM gr5n@nih.gov RI Kato, Gregory/I-7615-2014; OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809 FU Intramural NIH HHS [ZIA HL006012-02, ZIA HL006012-01] NR 25 TC 29 Z9 29 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2008 VL 141 IS 2 BP 254 EP 259 DI 10.1111/j.1365-2141.2008.07045.x PG 6 WC Hematology SC Hematology GA 277CA UT WOS:000254189100014 PM 18318767 ER PT J AU Kanda, A Abecasis, G Swaroop, A AF Kanda, Atsuhiro Abecasis, Goncalo Swaroop, Anand TI Inflammation in the pathogenesis of age-related macular degeneration SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID COMPLEMENT FACTOR-H; EPITHELIAL-CELLS; FACTOR-B; VARIANT; RISK; SUSCEPTIBILITY; ASSOCIATION; POLYMORPHISM; INDIVIDUALS; LIPOFUSCIN C1 [Swaroop, Anand] NEI, NNRL, Natl Inst Hlth, Bethesda, MD 20892 USA. [Kanda, Atsuhiro; Swaroop, Anand] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Swaroop, Anand] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Swaroop, A (reprint author), NEI, NNRL, Natl Inst Hlth, Bldg 10-10B11,MSC1864, Bethesda, MD 20892 USA. EM swaroopa@nei.nih.gov RI Abecasis, Goncalo/B-7840-2010; OI Abecasis, Goncalo/0000-0003-1509-1825; Swaroop, Anand/0000-0002-1975-1141 FU Intramural NIH HHS; NEI NIH HHS [EY016862] NR 30 TC 32 Z9 33 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD APR PY 2008 VL 92 IS 4 BP 448 EP 450 DI 10.1136/bjo.2007.131581 PG 5 WC Ophthalmology SC Ophthalmology GA 279XH UT WOS:000254388200004 PM 18369057 ER PT J AU Mannes, AJ Shepherd, M Quezado, Z AF Mannes, Andrew J. Shepherd, Martha Quezado, Zena TI Resolution of diplopia with late treatment of post-dural puncture headache and intracranial hypotension SO CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Letter ID EPIDURAL BLOOD PATCH; NERVE PALSY; DURAL PUNCTURE C1 [Mannes, Andrew J.; Shepherd, Martha; Quezado, Zena] NIH, Bethesda, MD 20892 USA. RP Mannes, AJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM mannes@nih.gov RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU Intramural NIH HHS [ZIA CL009009-02] NR 4 TC 2 Z9 2 U1 0 U2 0 PU CANADIAN ANESTHESIOLOGISTS SOC PI TORONTO PA 1 EGLINTON AVE EAST, SUITE 208, TORONTO, ONTARIO M4P 3A1, CANADA SN 0832-610X J9 CAN J ANAESTH JI Can. J. Anaesth.-J. Can. Anesth. PD APR PY 2008 VL 55 IS 4 BP 256 EP 257 PG 2 WC Anesthesiology SC Anesthesiology GA 290SW UT WOS:000255143500017 PM 18378978 ER PT J AU Forooghian, F Cukras, C Chew, EY AF Forooghian, Farzin Cukras, Catherine Chew, Emily Y. TI Retinal angiomatous proliferation complicated by pigment epithelial tear following intravitreal bevacizumab treatment SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Letter ID OCCULT CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; ANASTOMOSES C1 [Forooghian, Farzin; Cukras, Catherine; Chew, Emily Y.] NIH, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999, ZIE EY000487-01] NR 7 TC 8 Z9 8 U1 0 U2 1 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD APR PY 2008 VL 43 IS 2 BP 246 EP 248 DI 10.3129/i08-017 PG 3 WC Ophthalmology SC Ophthalmology GA 290BU UT WOS:000255098500023 PM 18347638 ER PT J AU Miller, BA Chu, KC Hankey, BF Ries, LAG AF Miller, Barry A. Chu, Kenneth C. Hankey, Benjamin F. Ries, Lynn A. G. TI Cancer incidence and mortality patterns among specific Asian and Pacific Islander populations in the US SO CANCER CAUSES & CONTROL LA English DT Article DE cancer; incidence; mortality; race; ethnicity; Asian; Pacific Islander; SEER Program ID HISPANIC ETHNICITY; BREAST-CANCER; SAMOAN WOMEN; REGISTRY; MISCLASSIFICATION; RATES; EPIDEMIOLOGY; SURVEILLANCE; AMERICANS; CHINESE AB Objectives: We report cancer incidence, mortality, and stage distributions among Asians and Pacific Islanders (API) residing in the U.S. and note health disparities, using the cancer experience of the non-Hispanic white population as the referent group. New databases added to publicly available SEER*Stat software will enable public health researchers to further investigate cancer patterns among API groups. Methods: Cancer diagnoses among API groups occurring from 1 January 1998 to 31 December 2002 were included from 14 Surveillance, Epidemiology, and End Results (SEER) Program state and regional population-based cancer registries covering 54% of the U.S. API population. Cancer deaths were included from the seven states that report death information for detailed API groups and which cover over 68% of the total U.S. API population. Using detailed racial/ethnic population data from the 2000 decennial census, we produced incidence rates centered on the census year for Asian Indians/Pakistanis, Chinese, Filipinos, Guamanians, Native Hawaiians, Japanese, Kampucheans, Koreans, Laotians, Samoans, Tongans, and Vietnamese. State vital records offices do not report API deaths separately for Kampucheans, Laotians, Pakistanis, and Tongans, so mortality rates were analyzed only for the remaining API groups. Results: Overall cancer incidence rates for the API groups tended be lower than overall rates for non-Hispanic whites, with the exception of Native Hawaiian women (All cancers rate = 488.5 per 100,000 vs. 448.5 for non-Hispanic white women). Among the API groups, overall cancer incidence and death rates were highest for Native Hawaiian and Samoan men and women due to high rates for cancers of the prostate, lung, and colorectum among Native Hawaiian men; cancers of the prostate, lung, liver, and stomach among Samoan men; and cancers of the breast and lung among Native Hawaiian and Samoan women. Incidence and death rates for cancers of the liver, stomach, and nasopharynx were notably high in several of the API groups and exceeded rates generally seen for non-Hispanic white men and women. Incidence rates were lowest among Asian Indian/Pakistani and Guamanian men and women and Kampuchean women. Asian Indian and Guamanian men and women also had the lowest cancer death rates. Selected API groups had less favorable distributions of stage at diagnosis for certain cancers than non-Hispanic whites. Conclusions: Possible disparities in cancer incidence or mortality between specific API groups in our study and non-Hispanic whites (referent group) were identified for several cancers. Unfavorable patterns of stage at diagnosis for cancers of the colon and rectum, breast, cervix uteri, and prostate suggest a need for cancer control interventions in selected groups. The observed variation in cancer patterns among API groups indicates the importance of monitoring these groups separately, as these patterns may provide etiologic clues that could be investigated by analytic epidemiological studies. C1 [Miller, Barry A.; Ries, Lynn A. G.] NCI, NIH, Div Canc Control & Populat Sci, Surveillance Res Program,Canc Stat Branch, Bethesda, MD 20852 USA. [Chu, Kenneth C.] NCI, NIH, Ctr Reduce Canc Hlth Dispar, Dispar Res Branch, Bethesda, MD 20852 USA. [Hankey, Benjamin F.] Informat Management Serv Inc, Silver Spring, MD USA. RP Miller, BA (reprint author), NCI, NIH, Div Canc Control & Populat Sci, Surveillance Res Program,Canc Stat Branch, 6116 Execut Blvd,Suite 504, Bethesda, MD 20852 USA. EM millerb@mail.nih.gov NR 45 TC 180 Z9 183 U1 2 U2 16 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2008 VL 19 IS 3 BP 227 EP 256 DI 10.1007/s10552-007-9088-3 PG 30 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 275QS UT WOS:000254087300002 PM 18066673 ER PT J AU Schenck, AP Klabunde, CN Warren, JL Peacock, S Davis, WW Hawley, ST Pignone, M Ransohoff, DF AF Schenck, Anna P. Klabunde, Carrie N. Warren, Joan L. Peacock, Sharon Davis, William W. Hawley, Sarah T. Pignone, Michael Ransohoff, David F. TI Evaluation of claims, medical records, and self-report for measuring fecal occult blood testing among Medicare enrollees in fee for service SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLORECTAL-CANCER; SCREENING PROCEDURES; BENEFICIARIES; DISPARITIES; POPULATION; RATIONALE; AUDIT AB Background: There is no agreement on the best data source for measuring colorectal cancer (CRC) screening. Medicare claims have been used to measure CRC testing but the validity of using claims to measure fecal occult blood tests (FOBT) has not been established. Methods: We compared ascertainment of FOBT among three data sources: self-reports, Medicare claims, and medical records. Data were collected on FOBT use during the study window (1/1/1998 - 12/31/2002). Our study was conducted with North Carolina Medicare enrollees (N = 561) who had previously responded to a telephone survey on CRC tests. FOBT information was abstracted from respondents' physician office medical records and compared with self-reported FOBT use and Medicare claims for FOBT. Data sources were assessed for accuracy and completeness of FOBT reporting using sensitivity, specificity, positive predictive value, negative predictive value, and agreement. Results: Reporting of FOBT use in the prior year in medical records and Medicare claims agreed 82% of the time [95% confidence interval (95% CI), 79-85%]. FOBT 1-year use rates from self-report agreed with test use found in medical records 70% of the time (95% CI, 66-74%). The lowest agreement was between self-reported 1-year FOBT use and Medicare claims, which agreed 67% of the time (95% CI, 63-71%). Conclusions: No data source could be established as providing complete and valid information about FOBT use among Medicare enrollees, showing the difficulty of ascertaining test use rates for noninvasive, low-cost procedures conducted in multiple settings. Caution should be used when attempting to measure FOBT use with self-report, Medicare claims, or medical records. C1 [Schenck, Anna P.; Peacock, Sharon] Carolinas Ctr Med Excellence, Cary, NC 27511 USA. [Klabunde, Carrie N.; Warren, Joan L.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. [Davis, William W.] NCI, Div Canc Control & Populat Sci, Surveillance Res Program, Stat Res & Applicat Branch, Rockville, MD USA. [Hawley, Sarah T.] Univ Michigan, Div Gen Med, Ann Arbor, MI 48109 USA. [Pignone, Michael; Ransohoff, David F.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Pignone, Michael] Univ N Carolina, Cecil Sheps Ctr Hlth Serv Res, Chapel Hill, NC USA. [Ransohoff, David F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Schenck, AP (reprint author), Carolinas Ctr Med Excellence, 100 Regency Forest,Suite 200, Cary, NC 27511 USA. EM aschenck@ncqio.sdps.org OI Pignone, Michael/0000-0002-6657-7342 FU NCI NIH HHS [Y1 PC 1007] NR 29 TC 20 Z9 20 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2008 VL 17 IS 4 BP 799 EP 804 DI 10.1158/1055-9965.EPI-07-2620 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 288EM UT WOS:000254969000008 PM 18381471 ER PT J AU Lamerato, LE Marcus, PM Jacobsen, G Johnson, CC AF Lamerato, Lois E. Marcus, Pamela M. Jacobsen, Gordon Johnson, Christine Cole TI Recruitment in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial: The first phase of recruitment at Henry Ford Health System SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AFRICAN-AMERICAN WOMEN; CLINICAL-TRIALS; PREVENTION; OLDER; PARTICIPATION; STRATEGIES; RETENTION; COMMUNITY; MINORITIES; DONT AB Objective: Recruitment of healthy subjects to long-term randomized controlled trials (RCTs) of cancer prevention or early detection has proven to be a difficult task. To quantify recruitment yield as well as characteristics of successfully recruited participants, we examined recruitment outcomes at 1 of the 10 centers participating in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, a National Cancer Institute-funded RCT of cancer screening modalities. Materials and Methods: During the early recruitment phase of PLCO (1993-1997), data on recruitment outcome were collected at the Henry Ford Health System (HFHS) in Detroit, Michigan. In this phase, HFHS identified potential participants using patient databases. Records were used to assess recruitment success by age, sex, race, household income (using area-based U.S. Census data), and preexisting morbidity. Logistic regression was used to assess whether enrollment success differed significantly according to these factors. Results: Of 74,139 persons ages 55 to 74 invited by HFHS to participate, 8,250 (11%) enrolled. In multivariate analyses, the odds of enrolling were modestly but significantly higher for women, Caucasians, persons in their 60's, and persons living in census blocks with higher median household income. Persons with two or more preexisting morbidities had significantly lower odds of enrolling compared to those with one or no preexisting morbidities. Conclusions: These data suggest that only a small fraction of persons invited to enroll in long-term RCTs of cancer screening modalities actually do so. In this urban, Midwestern setting, certain characteristics including age, race, and income influenced recruitment success, albeit modestly. C1 [Lamerato, Lois E.; Jacobsen, Gordon; Johnson, Christine Cole] Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI 48125 USA. [Marcus, Pamela M.] NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Lamerato, LE (reprint author), Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, 1 Ford Pl 5C, Detroit, MI 48125 USA. EM llamera1@hfhs.org OI Johnson, Christine Cole/0000-0002-6864-6604 FU NCI NIH HHS [N01 CN25404, N01 CN25522, N01 CN25516, N01 CN75022] NR 33 TC 8 Z9 8 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2008 VL 17 IS 4 BP 827 EP 833 DI 10.1158/1055-9965.EPI-06-0528 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 288EM UT WOS:000254969000013 PM 18398023 ER PT J AU Freedman, DM Chang, SC Falk, RT Purdue, MP Huang, WY McCarty, CA Hollis, BW Graubard, BI Berg, CD Ziegler, RG AF Freedman, D. Michal Chang, Shih-Chen Falk, Roni T. Purdue, Mark P. Huang, Wen-Yi McCarty, Catherine A. Hollis, Bruce W. Graubard, Barry I. Berg, Christine D. Ziegler, Regina G. TI Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID 25-HYDROXYVITAMIN-D; 1,25-DIHYDROXYVITAMIN-D; MORTALITY; SUNLIGHT; COLON AB Experimental and epidemiologic studies suggest that vitamin D metabolites (1,25-dihydroxyvitamin D [1,25(OH)(2)D] and its precursor 25-hydroxyvitamin D [25(OH)D]) may reduce breast cancer risk. We examined subsequent breast cancer risk related to serum levels of these metabolites. In a cohort of women ages 55 to 74 years, who donated blood at baseline (1993-2001) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we identified 1,005 incident breast cancer cases during follow-up through 2005 (mean time between blood draw and diagnosis, 3.9 years). Noncases (n = 1,005) were frequency matched to the cases based on age and year of entry. Sample weights that accounted for unequal probabilities of selecting cases and noncases were applied to make inferences that reflected the entire Prostate, Lung, Colorectal, and Ovarian cohort. Using Cox proportional hazards modeling, we computed breast cancer relative risks (RR) and 95% confidence intervals (95% CD by quintile for each metabolite. The RR of breast cancer for the highest quintile of 25(OH)D concentration versus the lowest was 1.04 (95% CI, 0.75-1.45; P-trend = 0.81). Similarly, the breast cancer RR for the highest quintile of 1,25(OH)(2)D compared with the lowest was 1.23 (95% CI, 0.91-1.68; P-trend = 0.14). Excluding the first 2 years of follow-up did not materially alter these estimates. There was also no evidence of inverse risk in older women (>= 60 years) versus younger women (<60 years). In this prospective study of postmenopausal women, we did not observe an inverse association between circulating 25(OH)D or 1,25(OH)(2)D and breast cancer risk, although we cannot exclude an association in younger women or with long-term or earlier exposure. C1 [Freedman, D. Michal; Chang, Shih-Chen; Falk, Roni T.; Purdue, Mark P.; Huang, Wen-Yi; Graubard, Barry I.; Ziegler, Regina G.] NCI, NIH, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Berg, Christine D.] NCI, NIH, Div Canc Prevent, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [McCarty, Catherine A.] Marshfield Clin Res Fdn, Marshfield, WI USA. [Hollis, Bruce W.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Freedman, DM (reprint author), NCI, NIH, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, EPS Room 7036,6120 Execut Blvd, Bethesda, MD 20892 USA. EM mf101e@nih.gov RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU Intramural NIH HHS [Z01 CP010152-09] NR 33 TC 100 Z9 102 U1 2 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2008 VL 17 IS 4 BP 889 EP 894 DI 10.1158/1055-9965.EPI-07-2594 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 288EM UT WOS:000254969000021 PM 18381472 ER PT J AU Schouten, LJ Rivera, C Hunter, DJ Spiegelman, D Adami, HO Arslan, A Beeson, WL van den Brandt, PA Buring, JE Folsom, AR Fraser, GE Freudenheim, JL Goldbohm, RA Hankinson, SE Lacey, JV Leitzmann, M Lukanova, A Marshall, JR Miller, AB Patel, AV Rodriguez, C Rohan, TE Ross, JA Wolk, A Zhang, SMM Smith-Warner, SA AF Schouten, Leo J. Rivera, Christine Hunter, David J. Spiegelman, Donna Adami, Hans-Olov Arslan, Alan Beeson, W. Lawrence van den Brandt, Piet A. Buring, Julie E. Folsom, Aaron R. Fraser, Gary E. Freudenheim, Jo L. Goldbohm, R. Alexandra Hankinson, Susan E. Lacey, James V., Jr. Leitzmann, Michael Lukanova, Annekatrin Marshall, James R. Miller, Anthony B. Patel, Alpa V. Rodriguez, Carmen Rohan, Thomas E. Ross, Julie A. Wolk, Alicja Zhang, Shumin M. Smith-Warner, Stephanie A. TI Height, body mass index, and ovarian cancer: A pooled analysis of 12 cohort studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SELF-REPORTED WEIGHT; GROWTH-FACTOR-I; UNITED-STATES; RISK-FACTORS; BREAST-CANCER; SEX-HORMONES; ANTHROPOMETRIC MEASUREMENTS; PHYSICAL-ACTIVITY; MENOPAUSAL STATUS; IGF-I AB Background: Although many studies have investigated the association between anthropometry and ovarian cancer risk, results have been inconsistent. Methods: The associations of height, body mass index (BMI), and ovarian cancer risk were examined in a pooled analysis of primary data from 12 prospective cohort studies from North America and Europe. The study population consisted of 531,583 women among whom 2,036 epithelial ovarian cancer cases were identified. To summarize associations, study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Results: Women with height >= 1.70 m had a pooled multivariate RR of 1.38 [95% confidence interval (95% CI), 1.16-1-65] compared with those with height <1.60 m. For the same comparison, multivariate RRs were 1.79 (95% CI, 1.07-3.00) for premenopausal and 1.25 (95% CI, 1.04-1.49) for postmenopausal ovarian cancer (P(interaction) = 0.14). The multivariate RR for women with a BMI >= 30 kg/m(2) was 1.03 (95% CI, 0.86-1.22) compared with women with a BMI from 18.5 to 23 kg/m(2). For the same comparison, multivariate RRs were 1.72 (95% CI, 1.02-2.89) for premenopausal and 1.07 (95% CI, 0.87-1.33) for postmenopausal women (P(interaction) = 0.07). There was no statistically significant heterogeneity between studies with respect to height or BMI. BMI in early adulthood was not associated with ovarian cancer risk. Conclusion: Height was associated with an increased ovarian cancer risk, especially in premenopausal women. BMI was not associated with ovarian cancer risk in postmenopausal women but was positively associated with risk in premenopausal women. C1 [Schouten, Leo J.; van den Brandt, Piet A.] Maastricht Univ, Dept Epidemiol, GROW Sch Oncol & Dev Biol, NL-6200 MD Maastricht, Netherlands. [Rivera, Christine; Hunter, David J.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. [Hunter, David J.; Spiegelman, Donna; Adami, Hans-Olov; Hankinson, Susan E.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. [Hunter, David J.; Hankinson, Susan E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. [Hunter, David J.; Hankinson, Susan E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Buring, Julie E.; Zhang, Shumin M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Adami, Hans-Olov] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Wolk, Alicja] Karolinska Inst, Dept Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. [Arslan, Alan] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. [Beeson, W. Lawrence; Fraser, Gary E.] Loma Linda Univ, Sch Med, Ctr Hlth Res, Loma Linda, CA USA. [Folsom, Aaron R.; Ross, Julie A.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Freudenheim, Jo L.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Goldbohm, R. Alexandra] Netherlands Org Appl Sci Res Qual Life, Dept Food & Chem Risk Anal, Zeist, Netherlands. [Lacey, James V., Jr.; Leitzmann, Michael] NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Miller, Anthony B.] Univ Toronto, Fac Med, Dept Publ Hlth Sci, Toronto, ON, Canada. [Patel, Alpa V.; Rodriguez, Carmen] Amer Canc Soc, Atlanta, GA 30329 USA. [Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Schouten, LJ (reprint author), Maastricht Univ, Dept Epidemiol, GROW Sch Oncol & Dev Biol, POB 616, NL-6200 MD Maastricht, Netherlands. EM lj.schouten@epid.unimaas.nl RI Schouten, Leo/G-3713-2012 FU NCI NIH HHS [CA 55075, P01 CA055075, R01 CA039742, R01 CA039742-24] NR 84 TC 72 Z9 72 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2008 VL 17 IS 4 BP 902 EP 912 DI 10.1158/1055-9965.EPI-07-2524 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 288EM UT WOS:000254969000023 PM 18381473 ER PT J AU Jacobs, EJ Hsing, AW Bain, EB Stevens, VL Wang, YT Chen, JB Chanock, SJ Zheng, SL Xu, JF Thun, MJ Calle, EE Rodriguezi, C AF Jacobs, Eric J. Hsing, Ann W. Bain, Elizabeth B. Stevens, Victoria L. Wang, Yiting Chen, Jinbo Chanock, Stephen J. Zheng, S. Lilly Xu, Jianfeng Thun, Michael J. Calle, Eugenia E. Rodriguezi, Carmen TI Polymorphisms in angogenesis-related genes and prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INDUCIBLE FACTOR-I; EPIDERMAL-GROWTH-FACTOR; NITRIC-OXIDE; ALPHA GENE; ANGIOGENESIS; EXPRESSION; HIF; SUSCEPTIBILITY; IDENTIFICATION; ASSOCIATION AB Background: Angiogenesis is required for development and progression of prostate cancer. Potentially functional single nucleotide polymorphisms (SNP) in genes important in prostate angiogenesis (VEGF, HIF1A, and NOS3) have previously been associated with risk or severity of prostate cancer. Methods: Prostate cancer cases (n = 1,425) and controls (n = 1,453) were selected from the Cancer Prevention Study 11 Nutrition Cohort. We examined associations between 58 SNPs in nine angiogenesis-related candidate genes (EGF, LTA, HIF1A, HIF1AN, MMP2, MMP9, NOS2A, NOS3, VEGF) and risk of overall and advanced prostate cancer. Unconditional logistic regression was used to estimate odds ratios, adjusted for matching factors. Results: Our results did not replicate previously observed associations with SNPs in VEGF, HIF1A, or NOS3, nor did we observe associations with SNPs in EGF, LTA, HIF1AN, MMP9, or NOS2A. In the MMP2 gene, three intronic SNPs, all in linkage disequilibrium, were associated with overall and advanced prostate cancer (for overall prostate cancer, P-trend = 0.01 for rs1477017, P-trend = 0.01 for rs17301608, P-trend 0.02 for rs11639960). However, two of these SNPs (rs17301608 and rs11639960) were examined and were not associated with prostate cancer in a recent genome-wide association study using prostate cancer cases and controls from the Prostate, Lung, Colorectal, and Ovary study cohort. Furthermore, when we pooled our results for these two SNPs with those from the Prostate, Lung, Colorectal, and Ovary cohort; neither SNP was associated with prostate cancer. Conclusion: None of the SNPs examined seem likely to be importantly associated with risk of overall or advanced prostate cancer. C1 [Jacobs, Eric J.; Bain, Elizabeth B.; Stevens, Victoria L.; Wang, Yiting; Thun, Michael J.; Calle, Eugenia E.; Rodriguezi, Carmen] Amer Canc Soc, Natl Home Off, Dept Epidemiol & Surveillance Res, Atlanta, GA 30303 USA. [Hsing, Ann W.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chen, Jinbo] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Zheng, S. Lilly; Xu, Jianfeng] Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27109 USA. RP Jacobs, EJ (reprint author), Amer Canc Soc, Natl Home Off, Dept Epidemiol & Surveillance Res, 250 Williams St, Atlanta, GA 30303 USA. EM Eric.Jacobs@cancer.org FU Intramural NIH HHS NR 27 TC 44 Z9 46 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2008 VL 17 IS 4 BP 972 EP 977 DI 10.1158/1055-9965.EPI-07-2787 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 288EM UT WOS:000254969000032 PM 18398039 ER PT J AU Bhatti, P Sigurdson, AJ Thomas, CB Iwan, A Alexander, BH Kampa, D Bowen, L Doody, MM Jones, IM AF Bhatti, Parveen Sigurdson, Alice J. Thomas, Cynthia B. Iwan, Allison Alexander, Bruce H. Kampa, Diane Bowen, Laura Doody, Michele Morin Jones, Irene M. TI No evidence for differences in DNA damage assessed before and after a cancer diagnosis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID US RADIOLOGIC TECHNOLOGISTS; IONIZING-RADIATION EXPOSURE; BREAST-CANCER; THYROID-CANCER; COMET ASSAY; REPAIR; GENES; RISK; POLYMORPHISMS; INSTABILITY AB The overwhelming majority of studies that have found increased cancer risk associated with functional deficits in DNA repair used a case-control design, in which measurements were made after cancer diagnosis. However, there are concerns about whether the cancer itself or cancer treatment affected the conclusions (reverse causation bias). We assessed the effect of cancer diagnosis among 26 breast cancer controls who had blood collected during 2001 to 2003 and again in 2005 to 2006 after being diagnosed with cancer. Using the alkaline comet assay, we quantified DNA damage in untreated lymphoblastoid cell lines. Comet distributed moment, olive tail moment, percentage of DNA in tail, and comet tail length were summarized as the geometric mean of 100 cells. For comet distributed moment, olive tail moment, tail DNA, and tail length, the proportions of women with before diagnosis values higher than after diagnosis were 65%, 50%, 50%, and 46%, respectively. We found no significant differences in the before or after diagnosis mean comet values. Median cut-points were determined from the before diagnosis distribution, and we used conditional logistic regression to calculate odds ratios (OR) and upper 95% bounds of the confidence intervals. ORs ranged from 0.6 to 0.9 with upper confidence interval bounds of 1.9 and 2.6, meaning biased ORs above 2.6 are unlikely. We found no evidence that reverse causation bias is an important concern in case-control studies using the comet assay applied to cell lines collected after cancer diagnosis. More work is needed to characterize the effect of cancer diagnosis on other phenotypic assays. C1 [Bhatti, Parveen; Sigurdson, Alice J.; Doody, Michele Morin] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Iwan, Allison; Alexander, Bruce H.; Kampa, Diane] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA. [Thomas, Cynthia B.; Jones, Irene M.] Lawrence Livermore Natl Lab, Livermore, CA USA. [Bowen, Laura] Informat Management Serv Inc, Silver Spring, MD USA. RP Bhatti, P (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM bhattip@mail.nih.gov FU Intramural NIH HHS [ZIA CP010133-18] NR 17 TC 7 Z9 7 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2008 VL 17 IS 4 BP 990 EP 994 DI 10.1158/1055-9965.EPI-07-2871 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 288EM UT WOS:000254969000036 PM 18398043 ER PT J AU Ye, XB Fitzgerald, EF Gomez, MI Lambert, GH Longnecker, MP AF Ye, Xibiao Fitzgerald, Edward F. Gomez, Marta I. Lambert, George H. Longnecker, Matthew P. TI The ratio of specific polychlorinated biphenyls as a surrogate biomarker of cytochrome P4501A2 activity - A pharmaco-metabonomic study in humans SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CYP1A2; POLYMORPHISMS C1 [Ye, Xibiao; Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Fitzgerald, Edward F.] SUNY Albany, Sch Publ Hlth, Rensselaer, NY USA. [Gomez, Marta I.] New York State Dept Hlth, Ctr Environm Hlth, Troy, NY USA. [Lambert, George H.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM longnec1@niehs.nih.gov RI Fitzgerald, Edward/F-4087-2010; OI Longnecker, Matthew/0000-0001-6073-5322 FU Intramural NIH HHS [ZIA ES049016-14]; NIEHS NIH HHS [ES 11256, 2 P42 ES 04913] NR 10 TC 0 Z9 0 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2008 VL 17 IS 4 BP 1013 EP 1015 DI 10.1158/1055-9965.EPI-08-0040 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 288EM UT WOS:000254969000041 PM 18398048 ER PT J AU Worschech, A Kmieciak, M Knutson, KL Bear, HD Szalay, AA Wang, E Marincola, FM Manjili, MH AF Worschech, Andrea Kmieciak, Maciej Knutson, Keith L. Bear, Harry D. Szalay, Aladar A. Wang, Ena Marincola, Francesco M. Manjili, Masoud H. TI Signatures associated with rejection or recurrence in HER-2/neu-positive mammary tumors SO CANCER RESEARCH LA English DT Article ID REGULATORY T-CELLS; COLORECTAL-CANCER; MELANOMA PATIENTS; IMMUNE-RESPONSES; TRANSGENIC MICE; EXPRESSION PATTERNS; GENE-EXPRESSION; DENDRITIC CELLS; IN-VITRO; MACROPHAGES AB We have previously shown T-cell-mediated rejection of the neu-overexpressing mammary carcinoma cells (MAIC) in wildtype FVB mice. However, following rejection of primary tumors, a fraction of animals experienced a recurrence of a neu antigen-negative variant (ANV) of MMC (tumor evasion model) after a long latency period. In the present study, we determined that T cells derived from wild-type FVB mice can specifically recognize MMC by secreting IFN-gamma and can induce apoptosis of MAIC in vitro. Neu transgenic (FVBN202) mice develop spontaneous tumors and cannot reject it (tumor tolerance model). To dissect the mechanisms associated with rejection or tolerance of MMC tumors, we compared transcriptional patterns within the tumor microenvironment of MAIC undergoing rejection with those that resisted it either because of tumor evasion/antigen loss recurrence (ANV tumors) or because of intrinsic tolerance mechanisms displayed by the transgenic mice. Gene profiling confirmed that immune rejection is primarily mediated through activation of IFN-stimulated genes and T-cell effector mechanisms. The tumor evasion model showed combined activation of Th1 and Th2 with a deviation toward Th2 and Immoral immune responses that failed to achieve rejection likely because of lack of target antigen. Interestingly, the tumor tolerance model instead displayed immune suppression pathways through activation of regulatory mechanisms that included in particular the overexpression of interleukin-10 (IL-10), IL-10 receptor, and suppressor of cytokine signaling (SOCS)-1 and SOCS-3. These data provide a road map for the identification of novel biomarkers of immune responsiveness in clinical trials. C1 [Kmieciak, Maciej; Manjili, Masoud H.] Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, Massey Canc Ctr, Richmond, VA 23298 USA. [Bear, Harry D.] Virginia Commonwealth Univ, Sch Med, Dept Surg, Massey Canc Ctr, Richmond, VA 23298 USA. [Worschech, Andrea; Wang, Ena; Marincola, Francesco M.] NIH, Dept Transfus Med, Immunogenet Lab, Bethesda, MD 20892 USA. [Worschech, Andrea; Szalay, Aladar A.] Genelux Corp, San Diego Sci Ctr, San Diego, CA USA. [Worschech, Andrea] Univ Wurzburg, Inst Biochem, Wurzburg, Germany. [Szalay, Aladar A.] Univ Wurzburg, Virchow Ctr Expt Biomed, Inst Biochem, Wurzburg, Germany. [Szalay, Aladar A.] Univ Wurzburg, Inst Mol Infect Biol, Wurzburg, Germany. [Knutson, Keith L.] Mayo Clin, Coll Med, Dept Immunol, Rochester, MN USA. RP Manjili, MH (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, Massey Canc Ctr, Box 980035,401 Coll St, Richmond, VA 23298 USA. EM mmanjili@vcu.edu RI Worschech, Andrea/I-3919-2012 OI Worschech, Andrea/0000-0002-4303-8653 FU NCI NIH HHS [P30 CA016059, P30CA16059, R01 CA104757, R01 CA104757-03] NR 51 TC 33 Z9 33 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 APR 1 PY 2008 VL 68 IS 7 BP 2436 EP 2446 DI 10.1158/0008-5472.CAN-07-6822 PG 11 WC Oncology SC Oncology GA 284WU UT WOS:000254738500047 PM 18381452 ER PT J AU Wang, SS Smiraglia, DJ Wu, YZ Ghosh, S Rader, JS Cho, KR Bonfiglio, TA Nayar, R Plass, C Sherman, ME AF Wang, Sophia S. Smiraglia, Dominic J. Wu, Yue-Zhong Ghosh, Srimoyee Rader, Janet S. Cho, Kathleen R. Bonfiglio, Thomas A. Nayar, Ritu Plass, Christoph Sherman, Mark E. TI Identification of novel methylation markers in cervical cancer using restriction landmark genomic scanning SO CANCER RESEARCH LA English DT Article ID CPG ISLAND HYPERMETHYLATION; TUMOR-SUPPRESSOR GENE; DNA METHYLATION; PROMOTER HYPERMETHYLATION; ABERRANT METHYLATION; CELL-LINES; NUCLEOLAR PROTEIN; NEOPLASIA; CARCINOMA; FREQUENT AB Aberrant methylation of CpG islands in gene promoters often represents an early clonal event in carcinogenesis. Accordingly, defining methylation profiles may be useful for developing marker panels for early detection or predicting the risk of cancer precursors. To identify specific genes frequently methylated in cervical cancer, we conducted methylation profiling of 20 primary human cervical cancers using NotI-based restriction landmark genomic scanning (RLGS). Of 2,172 RLGS fragments analyzed (average, 1,753 CpG islands per patient), 186 RLGS fragments were lost in at least one tumor and 40 were lost in three or more. Methylation was identified in 19 (95%) of 20 tumor samples compared with normal DNA. Bisulfite sequencing was conducted to confirm RLGS results. Of the confirmed markers frequently methylated, we developed Methylight assays for two corresponding genes, nucleolar protein 4 (NOL4), and lipoma HMGIC fusion partner-like protein 4 (LHFPL4), which were methylated in 85% and 55% of cancers, respectively. Using these assays, we further confirmed frequent CpG island methylation in the original cancers and in another independent series of 15 cervical cancers. We also showed methylation at a reduced frequency in a set of carefully reviewed cytology specimens demonstrating cells exfoliated from cancer precursor lesions. In summary, we identified, for the first time, NOL4 and LHFPL4 as novel methylation targets specific for cervical cancer. Inclusion of NOL4 and LHFPL4 in evaluating methylation panels for early detection, risk prediction, and etiologic research on cervical cancer is warranted. C1 [Wang, Sophia S.; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Smiraglia, Dominic J.; Ghosh, Srimoyee] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. [Wu, Yue-Zhong; Plass, Christoph] Ohio State Univ, Div Human Canc Genet, Columbus, OH 43210 USA. [Rader, Janet S.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. [Cho, Kathleen R.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. [Cho, Kathleen R.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Bonfiglio, Thomas A.] Univ Rochester, Sch Med, Dept Pathol & Lab Med, Rochester, NY USA. [Nayar, Ritu] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. RP Wang, SS (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5104, Rockville, MD 20852 USA. EM wangso@mail.nih.gov RI Plass, Christoph/H-7192-2014; OI Smiraglia, Dominic/0000-0001-8852-1510 FU Intramural NIH HHS; NCI NIH HHS [CA94141, CA95713] NR 41 TC 36 Z9 36 U1 1 U2 3 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 APR 1 PY 2008 VL 68 IS 7 BP 2489 EP 2497 DI 10.1158/0008-5472.CAN-07-3194 PG 9 WC Oncology SC Oncology GA 284WU UT WOS:000254738500053 PM 18381458 ER PT J AU Liu, XX Allen, JD Arnold, JT Blackman, MR AF Liu, Xunxian Allen, Jeffrey D. Arnold, Julia T. Blackman, Marc R. TI Lycopene inhibits IGF-I signal transduction and growth in normal prostate epithelial cells by decreasing DHT-modulated IGF-I production in co-cultured reactive stromal cells SO CARCINOGENESIS LA English DT Article ID BETA-CATENIN; CANCER CELLS; ANDROGEN RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSCRIPTIONAL ACTIVITY; NUCLEAR TRANSLOCATION; PLASMA LYCOPENE; NUDE-MICE; AKT; APOPTOSIS AB Prostate stromal and epithelial cell communication is important in prostate functioning and cancer development. Primary human stromal cells from normal prostate stromal cells (PRSC) maintain a smooth muscle phenotype, whereas those from prostate cancer (6S) display reactive and fibroblastic characteristics. Dihydrotestosterone (DHT) stimulates insulin-like growth factor-I (IGF-I) production by 6S but not PSRC cells. Effects of reactive versus normal stroma on normal human prostate epithelial (NPE or PREC) cells are poorly understood. We co-cultured NPE plus 6S or PRSC cells to compare influences of different stromal cells on normal epithelium. Because NPE and PREC cells lose androgen receptor (AR) expression in culture, DHT effects must be modulated by associated stromal cells. When treated with camptothecin (CM), NPE cells, alone and in stromal co-cultures, displayed a dose-dependent increase in DNA fragmentation. NPE/6S co-cultures exhibited reduced CM-induced cell death with exposure to DHT, whereas NPE/PRSC co-cultures exhibited CM-induced cell death regardless of DHT treatment. DHT blocked CM-induced, IGF-I-mediated, NPE death in co-cultured NPE/6S cells without, but not with, added anti-IGF-I and anti-IGF-R antibodies. Lycopene consumption is inversely related to human prostate cancer risk and inhibits IGF-I and androgen signaling in rat prostate cancer. In this study, lycopene, in dietary concentrations, reversed DHT effects of 6S cells on NPE cell death, decreased 6S cell IGF-I production by reducing AR and beta-catenin nuclear localization and inhibited IGF-I-stimulated NPE and PREC growth, perhaps by attenuating IGF-I's effects on serine phosphorylation of Akt and GSK3 beta and tyrosine phosphorylation of GSK3. This study expands the understanding of the preventive mechanisms of lycopene in prostate cancer. C1 [Liu, Xunxian; Allen, Jeffrey D.; Arnold, Julia T.; Blackman, Marc R.] NIH, Endocrine Sect, Clin Invest Lab,Div Intramural Res, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Blackman, MR (reprint author), NIH, Endocrine Sect, Clin Invest Lab,Div Intramural Res, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. EM marc.blackman@va.gov FU Intramural NIH HHS NR 50 TC 31 Z9 33 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2008 VL 29 IS 4 BP 816 EP 823 DI 10.1093/carcin/bgn011 PG 8 WC Oncology SC Oncology GA 284CV UT WOS:000254683800019 PM 18283040 ER PT J AU Ji, XM Neumann, AS Sturgis, EM Adler-Storthz, K Dahlstrom, KR Schiller, JT Wei, QY Li, GJ AF Ji, Xuemei Neumann, Ana S. Sturgis, Erich M. Adler-Storthz, Karen Dahlstrom, Kristina R. Schiller, John T. Wei, Qingyi Li, Guojun TI p53 codon 72 polymorphism associated with risk of human papillomavirus-associated squamous cell carcinoma of the oropharynx in never-smokers SO CARCINOGENESIS LA English DT Article ID ORAL-CANCER; NECK-CANCER; CERVICAL-CANCER; HEAD; TYPE-16; DNA; INFECTION; E6; VARIANTS; VIRUS AB The tumor suppressor p53 protein can be bound, degraded and inactivated by the human papillomavirus (HPV) E6 oncoprotein. The p53 protein's susceptibility to this oncoprotein may be influenced by the p53 codon 72 polymorphism, but the role of such a polymorphism in the development of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP) has not been established. To investigate the role of the p53 codon 72 polymorphism in the risk of HPV16-associated SCCOP, we conducted a hospital-based case-control study of 188 non-Hispanic white patients with newly diagnosed SCCOP and 342 cancer-free control subjects frequency matched by age (+/- 5 years), sex, tobacco smoking status and alcohol drinking status. We found that HPV16 seropositivity was associated with an increased risk of SCCOP [adjusted odds ratio (OR), 5.7; 95% confidence interval (CI), 3.7-8.7], especially among never smokers (adjusted OR, 14.1; 95% CI, 6.0-32.9) and among subjects with the p53 codon 72 variant genotypes [Arginine (Arg)/Proline (Pro) and Pro/Pro] (adjusted OR, 9.2; 95% CI, 4.7-17.7). A significant multiplicative interaction on the risk of SCCOP was also found between the p53 codon 72 polymorphism and HPV16 seropositivity (P = 0.05). Among never- smokers, the risk of SCCOP for those who had both HPV16 seropositivity and p53 codon 72 variant genotypes (Arg/Pro + Pro/Pro) was particularly high (adjusted OR, 22.5; 95% CI, 4.8-106.2). These findings suggest that p53 codon 72 variant genotypes modify the risk of HPV16-associated SCCOP and may be markers of genetic susceptibility to HPV16-associated SCCOP, especially among never- smokers. C1 [Ji, Xuemei; Sturgis, Erich M.; Dahlstrom, Kristina R.; Li, Guojun] Univ Texas Houston, MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. [Neumann, Ana S.] Royal Childrens Hosp, Dent Div, Parkville, Vic 3052, Australia. [Adler-Storthz, Karen] Univ Texas Houston, Hlth Sci Ctr, Dent Branch, Dept Diagnost Sci, Houston, TX 77030 USA. [Dahlstrom, Kristina R.] Univ Washington, Dept Genet & Dev Med, Seattle, WA 98195 USA. [Schiller, John T.] NCI, NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Li, GJ (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Head & Neck Surg, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM gli@mdanderson.org RI Ji, Xuemei/B-9774-2015 OI Ji, Xuemei/0000-0001-7416-9122 FU NCI NIH HHS [P50CA097007, CA 16672, K-12 CA88084] NR 48 TC 29 Z9 31 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2008 VL 29 IS 4 BP 875 EP 879 DI 10.1093/carcin/bgn039 PG 5 WC Oncology SC Oncology GA 284CV UT WOS:000254683800028 PM 18258602 ER PT J AU Poruchynsky, MS Sackett, DL Robey, RW Ward, Y Annunziata, C Fojo, T AF Poruchynsky, Marianne S. Sackett, Dan L. Robey, Robert W. Ward, Yvona Annunziata, Christina Fojo, Tito TI Proteasome inhibitors increase tubulin polymerization and stabilization in tissue culture cells - A possible mechanism contributing to peripheral neuropathy and cellular toxicity following proteasome inhibition SO CELL CYCLE LA English DT Article DE tubulin; polymerization; multiple myeloma; proteasome inhibitors; neurotoxicity; microtubule stabilization; alpha-tubulin acetylation ID MULTIPLE-MYELOMA; BETA-TUBULIN; CANCER-CELLS; PROTEIN-DEGRADATION; IN-VIVO; INCLUSION-BODIES; DRUG-RESISTANCE; BREAST-CANCER; ALPHA-TUBULIN; BORTEZOMIB AB Bortezomib (Velcade((R))), a proteasome inhibitor, is approved by the FDA for the treatment of multiple myeloma (MM). While effective, its use has been hampered by peripheral neurotoxicity of unexplained etiology. Since proteasome inhibitors alter protein degradation, we speculated that proteins regulating microtubule (MT) stability may be affected after treatment and examined MT polymerization in cells by comparing the distribution of tubulin between polymerized (P) and soluble (S) fractions. We observed increased MT polymerization following treatment of SY5Y and KCNR [neuroblastoma], HCN2 and 8226 [MM] cells, using five proteasome inhibitors; the baseline proportion of total a-tubulin in 'P' fractions ranged from similar to 41 - 68%, and increased to similar to 55 - 99% after treatment. Increased acetylated alpha-tubulin, a post-translational marker of stabilized MTs, was observed in the neural cell lines HCN1A and HCN2 and this was sustained up to 144 hours after the proteasome inhibitor was removed. Cell cycle analysis of three cell lines after treatment, showed similar to 50 - 75% increases in the G(2)M phase. Immunofluorescent localization studies of proteasome inhibitor treated cells did not reveal microtubule bundles in contrast to paclitaxel treated, suggesting MT stabilization via a mechanism other than direct drug binding. We examined the levels of microtubule associated proteins and observed a 1.4 - 3.7 fold increase in the microtubule associated protein MAP2, in HCN2 cells following treatment with proteasome inhibitors. These data provide a plausible explanation for the neurotoxicity observed clinically and raise the possibility that microtubule stabilization contributes to cytotoxicity. C1 [Poruchynsky, Marianne S.; Robey, Robert W.; Annunziata, Christina; Fojo, Tito] NCI, Expt Therapeut Sect, Med Oncol Br, CCR, Bethesda, MD 20892 USA. [Ward, Yvona] NCI, Expt Therapeut Sect, Cell & Canc Biol Branch, CCR, Bethesda, MD 20892 USA. [Sackett, Dan L.] NICHHD, NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Expt Therapeut Sect, Med Oncol Br, CCR, 10 Ctr Dr,Bldg 10,Rm 13N240,MSC 1902, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 FU Intramural NIH HHS NR 57 TC 46 Z9 49 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 APR 1 PY 2008 VL 7 IS 7 BP 940 EP 949 PG 10 WC Cell Biology SC Cell Biology GA 291TK UT WOS:000255219500018 PM 18414063 ER PT J AU Li, X Luo, Y Yu, L Lin, Y Luo, D Zhang, H He, Y Kim, YO Kim, Y Tang, S Min, W AF Li, X. Luo, Y. Yu, L. Lin, Y. Luo, D. Zhang, H. He, Y. Kim, Y-O Kim, Y. Tang, S. Min, W. TI SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; ASK1; HIPK1; SENP1; TNF ID REGULATING KINASE 1; HOMEODOMAIN-INTERACTING PROTEIN-KINASE-1; INDUCED ASK1 ACTIVATION; SUMO-SPECIFIC PROTEASE; ASK1-MEDIATED APOPTOSIS; SERINE/THREONINE KINASE; SIGNAL-TRANSDUCTION; INHIBITOR 14-3-3; MAP KINASES; CELL-DEATH AB We have previously shown that tumor necrosis factor (TNF)-induced desumoylation and subsequent cytoplasmic translocation of HIPK1 are critical for ASK1-JNK activation. However, the mechanism by which TNF induces desumoylation of HIPK1 is unclear. Here, we show that SENP1, a SUMO-specific protease, specifically deconjugates SUMO from HIPK1 in vitro and in vivo. In resting endothelial cells (ECs), SENP1 is localized in the cytoplasm where it is complexed with an antioxidant protein thioredoxin. TNF induces the release of SENP1 from thioredoxin as well as nuclear translocation of SENP1. TNF-induced SENP1 nuclear translocation is specifically blocked by antioxidants such as N-acetyl-cysteine, suggesting that TNF-induced translocation of SENP1 is ROS dependent. TNF-induced nuclear import of SENP1 kinetically correlates with HIPK1 desumoylation and cytoplasmic translocation. Furthermore, the wild-type form of SENP1 enhances, whereas the catalytic-inactive mutant form or siRNA of SENP1 blocks, TNF-induced desumoylation and cytoplasmic translocation of HIPK1 as well as TNF-induced ASK1-JNK activation. More importantly, these critical functions of SENP1 in TNF signaling were further confirmed in mouse embryonic fibroblast cells derived from SENP1-knockout mice. We conclude that SENP1 mediates TNF-induced desumoylation and translocation of HIPK1, leading to an enhanced ASK1-dependent apoptosis. C1 [Li, X.; Luo, Y.; Yu, L.; Lin, Y.; Luo, D.; Zhang, H.; He, Y.; Min, W.] Yale Univ, Sch Med, Dept Pathol, Interdept Program Vasc Biol & Transplantat, New Haven, CT 06510 USA. [Li, X.] So Med Univ, Nanfang Hosp, Dept Hepatobiliary Surg, Beijing, Peoples R China. [Luo, Y.; Tang, S.] Sun Yat Sen Univ, Zhongshan Ophthal Ctr, State Key Lab Ophthalmol, Guangzhou, Peoples R China. [Kim, Y-O; Kim, Y.] NHLBI, NIH, Lab Res Program, Bethesda, MD 20892 USA. RP Min, W (reprint author), Yale Univ, Sch Med, Dept Pathol, Interdept Program Vasc Biol & Transplantat, BCMM 454,295 Congress Ave, New Haven, CT 06510 USA. EM wang.min@yale.edu RI Yu, Luyang/C-2198-2011 FU NHLBI NIH HHS [R01 HL-65978-5, P01HL070295-6] NR 44 TC 40 Z9 44 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD APR PY 2008 VL 15 IS 4 BP 739 EP 750 DI 10.1038/sj.cdd.4402303 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 274ZR UT WOS:000254041800017 PM 18219322 ER PT J AU Byts, N Samoylenko, A Fasshauer, T Ivanisevic, M Hennighausen, L Ehrenreich, H Siren, AL AF Byts, N. Samoylenko, A. Fasshauer, T. Ivanisevic, M. Hennighausen, L. Ehrenreich, H. Siren, A-L TI Essential role for Stat5 in the neurotrophic but not in the neuroprotective effect of erythropoietin SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE process length; ifenprodil; D-AP-5; cucurbitacin I; LY294002; NMDA ID POTENT ANTITUMOR-ACTIVITY; NF-KAPPA-B; IN-VITRO; GROWTH-HORMONE; CEREBRAL-ISCHEMIA; MEDIATED NEUROPROTECTION; MAMMALIAN FOREBRAIN; NEURONAL APOPTOSIS; SIGNAL TRANSDUCERS; BRAIN-DEVELOPMENT AB The transcription factors signal transducer and activator of transcription 5a and 5b (Stat5) are activated by the neuroprotective and neurotrophic cytokines, erythropoietin (EPO) and growth hormone (GH). Here, we show a dissociation of the intracellular pathway mediating the protective effect of EPO against glutamate toxicity from that needed for its neurotrophic activity using hippocampal neuronal cultures from Stat5a/b-knockout (Stat5(-/-)) mouse fetuses. Both pretreatment and post-treatment with EPO counteracted glutamate-induced cell death in Stat5(+/+) and Stat5(-/-) neurons. Acute pharmacological inhibition of Janus kinase 2 (JAK2)/Stat signalling had no effect on EPO neuroprotection, whereas inhibition of phosphatidylinositol-3 ' kinase (PI3K)/Akt pathway abolished the protective effect of EPO in both Stat5(+/+) and Stat5(-/-) neurons. GH effectively protected Stat5(+/+) cells against glutamate toxicity but had no effect in Stat-/- neurons or in Stat5(+/+) neurons treated with JAK2/Stat or PI3K inhibitor. EPO and GH stimulated neurite outgrowth and branching of Stat5(+/+) neurons by activating PI3K/Akt signalling but had no trophic effect in Stat5(-/-) cells. We conclude that in hippocampal neurons, Stat5 is not required for neuroprotection by EPO but is together with Akt essential for its neurotrophic activity. Both Stat5 and Akt are needed for neuroprotective and neurotrophic signalling of GH in neurons. C1 [Byts, N.; Samoylenko, A.; Fasshauer, T.; Ivanisevic, M.; Siren, A-L] Univ Wurzburg, Dept Neurosurg, Sect Expt Neurosurg, D-97080 Wurzburg, Germany. [Byts, N.; Ehrenreich, H.] Max Planck Inst Expt Med, Div Clin Neurosci, D-37075 Gottingen, Germany. [Hennighausen, L.] NIDDKD, Lab Genet & Phsiol, NIH, Bethesda, MD 20892 USA. RP Siren, AL (reprint author), Univ Wurzburg, Dept Neurosurg, Sect Expt Neurosurg, Josef Schneider St 11, D-97080 Wurzburg, Germany. EM siren.a@nch.uni-wuerzburg.de OI Siren, Anna-Leena/0000-0002-2217-0081; Ivanisevic , Marina /0000-0001-6478-1174 NR 40 TC 46 Z9 51 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD APR PY 2008 VL 15 IS 4 BP 783 EP 792 DI 10.1038/cdd.2008.1 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 274ZR UT WOS:000254041800021 PM 18259195 ER PT J AU Winkler, CA AF Winkler, Cheryl A. TI Identifying host targets for drug development with knowledge from genome-wide studies: Lessons from HIV-AIDS SO CELL HOST & MICROBE LA English DT Editorial Material ID VIRUS-INFECTION; PROGRESSION; RESISTANCE; SUSCEPTIBILITY; POLYMORPHISMS; RESTRICTION; REPLICATION; ASSOCIATION; RNA AB Advances in human genomics are now being effectively applied to the search for host factors underlying susceptibility to common diseases. From the steady stream of studies showing association of host genetic factors with viral diseases, it has become clear that host factors contribute substantially to the variability of viral infections in humans. Candidate gene studies that seek to show associations between sing le-nucleotide polymorphisms (SNPs) with a disease outcome have predominated, but whole-genome association studies (GWAS) have recently appeared. A major goal of these studies is to understand how human genetic variation contributes to individual differences in susceptibility and to exploit this knowledge for targeted drug development. C1 NCI, Lab Genom Divers, CCR, SAIC Frederick, Frederick, MD 21702 USA. RP Winkler, CA (reprint author), NCI, Lab Genom Divers, CCR, SAIC Frederick, Frederick, MD 21702 USA. EM winkler@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 18 TC 2 Z9 4 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD APR PY 2008 VL 3 IS 4 BP 203 EP 205 DI 10.1016/j.chom.2008.04.001 PG 3 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 293HK UT WOS:000255326100003 PM 18407063 ER PT J AU Matsusue, K Kusakabe, T Noguchi, T Takiguchi, S Suzuki, T Yamano, S Gonzalez, FJ AF Matsusue, Kimihiko Kusakabe, Takashi Noguchi, Takahiro Takiguchi, Shouichi Suzuki, Toshimitsu Yamano, Shigeru Gonzalez, Frank J. TI Hepatic steatosis in leptin-deficient mice is promoted by the PPAR gamma target gene Fsp27 SO CELL METABOLISM LA English DT Article ID DNA-FRAGMENTATION-FACTOR; PROLIFERATOR-ACTIVATED RECEPTORS; LOW-DENSITY LIPOPROTEINS; FATTY-ACID OXIDATION; TRANSCRIPTIONAL REGULATION; LIPID-ACCUMULATION; INSULIN-RESISTANCE; ADIPOSE-TISSUE; EXPRESSION; LIVER AB Peroxisome proliferator-activated receptor gamma (PPAR gamma) is induced in leptin-deficient(ob/ob) mouse liver and is critical for the development of hepatic steatosis. The present study shows that fat-specific protein 27 (Fsp27) in ob/ob liver is a direct target gene of PPAR gamma and can elevate hepatic triglyceride levels. FSP27 belongs to the CIDE family, composed of CIDE A, CIDE B, and FSP27/CIDE C, all of which contain a conserved CIDE-N domain. FSP27 was recently reported to be a lipid droplet-binding protein and to promote lipid accumulation in adipocytes. The Fsp27 gene was expressed at high levels in oblob liver and at markedly lower levels in oblob livers lacking PPAR gamma. Forced expression of FSP27 by adenovirus in hepatocytes in vitro or in vivo led to increased triglyceride levels. Knockdown by adenovirus expressing FSP27 shRNA resulted in lower accumulation of hepatic triglycerides compared to control adenovirus-infected liver. Taken together, these results indicate that FSP27 is a direct mediator of PPAR gamma-dependent hepatic steatosis. C1 [Matsusue, Kimihiko; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Matsusue, Kimihiko; Noguchi, Takahiro; Yamano, Shigeru] Fukuoka Univ, Fac Pharmaceut Sci, Jonan Ku, Fukuoka 8140180, Japan. [Kusakabe, Takashi; Suzuki, Toshimitsu] Fukushima Med Univ, Dept Pathol, Sch Med, Fukushima 9601295, Japan. [Takiguchi, Shouichi] Kyushu Natl Canc Ctr, Inst Clin Res, Minami Ku, Fukuoka 8111395, Japan. RP Matsusue, K (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM matsusuk@fukuoka-u.ac.jp FU Intramural NIH HHS [Z01 BC005708-15] NR 36 TC 165 Z9 176 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD APR PY 2008 VL 7 IS 4 BP 302 EP 311 DI 10.1016/j.cmet.2008.03.003 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 286ST UT WOS:000254867000009 PM 18396136 ER PT J AU Gerald, NJ Coppens, I Dwyer, DM AF Gerald, Noel J. Coppens, Isabelle Dwyer, Dennis M. TI Molecular characterization and expression of a novel kinesin which localizes with the kinetoplast in the human pathogen, Leishmania donovani SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE kinesin; Leishmania; kinetoplast; GFP; protozoan parasite ID PROTEIN SEQUENCES; DNA NETWORKS; REPLICATION; MECHANISM; PARASITE; PROMASTIGOTES; TRANSCRIPTION; AMASTIGOTES; SUPERFAMILY; TRANSPORT AB Using a variety of molecular and cell biological approaches, we identified, characterized and expressed a novel kinesin, LdK39B in the protozoan pathogen Leishmania donovani. Results of RT-PCR revealed two distinct LdK39B products with different splice leader mini-exon sites, indicative of two potentially mature mRNA transcripts. Analyses indicated that LdK39B had a calculated molecular mass of >261, 327 Da and contained multiple amino acid repeat units. Several GFP-LdK39B fusion constructs were generated and used for episomal-expression in these parasites. Results of confocal and immunoelectron microscopy indicated that the GFP-LdK39B-fusion proteins localized to a region adjacent to the flagellar pocket and the kinetoplast i.e. the mitochondrial-DNA containing organelle that is physically tethered to the flagellar basal bodies. Sub-cellular fractionation results showed that GFP-LdK39B proteins were insoluble in nature and remained tightly associated with purified flagella/kinetoplasts following their extraction with detergent and high salts. Our cumulative results suggest that the LdK39B may play a scaffold-like role in facilitating and maintaining the unique spatial/structural association between the flagellum-basal body-kinetoplast complex in these parasites. C1 [Gerald, Noel J.; Dwyer, Dennis M.] NIAID, Parasit Dis Lab, Cell Biol Sect, NIH, Bethesda, MD 20892 USA. [Coppens, Isabelle] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Bloomberg Sch Publ Hlth, Bethesda, MD USA. RP Dwyer, DM (reprint author), NIAID, Parasit Dis Lab, Cell Biol Sect, NIH, Bldg 4,Room 126,4 Ctr Dr MSC 0425, Bethesda, MD 20892 USA. EM ddwyer@niaid.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [AI060767] NR 37 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD APR PY 2008 VL 65 IS 4 BP 269 EP 280 DI 10.1002/cm.20259 PG 12 WC Cell Biology SC Cell Biology GA 284IA UT WOS:000254698900001 PM 18240272 ER PT J AU Bianco, P Robey, PG Simmons, PJ AF Bianco, Paolo Robey, Pamela Gehron Simmons, Paul J. TI Mesenchymal stem cells: Revisiting history, concepts, and assays SO CELL STEM CELL LA English DT Editorial Material ID THERAPY POSITION STATEMENT; HUMAN BONE-MARROW; STROMAL CELLS; INTERNATIONAL-SOCIETY; NICHE; PRECURSORS; PLASTICITY; INVITRO; MICROENVIRONMENT; TRANSPLANTATION AB The concept of mesenchymal stem cells has gained wide popularity. Despite the rapid growth of the field, uncertainties remain with respect to the defining characteristics of these cells, including their potency and self-renewal. These uncertainties are reflected in a growing tendency to question the very use of the term. This commentary revisits the experimental origin of the concept of the population(s) referred to as mesenchymal stem cells and the experimental framework required to assess their sternness and function. C1 [Bianco, Paolo] Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy. [Bianco, Paolo] Biomed Sci Pk San Raffaele, I-00128 Rome, Italy. [Robey, Pamela Gehron] Natl Inst Dent & Cranifacial Res, Craniofacial & Skeletal Dis Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Simmons, Paul J.] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA. RP Bianco, P (reprint author), Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy. EM paolo.bianco@uniroma1.it RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural NIH HHS [Z01 DE000380-24] NR 48 TC 625 Z9 694 U1 17 U2 70 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD APR PY 2008 VL 2 IS 4 BP 313 EP 319 DI 10.1016/j.stem.2008.03.002 PG 7 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 293HT UT WOS:000255327000008 PM 18397751 ER PT J AU Arcidiacono, D Odom, S Frossi, B Rivera, J Paccani, SR Baldari, CT Pucillo, C Montecucco, C de Bernard, M AF Arcidiacono, Diletta Odom, Sandra Frossi, Barbara Rivera, Juan Paccani, Silvia R. Baldari, Cosima T. Pucillo, Carlo Montecucco, Cesare de Bernard, Marina TI The Vibrio cholerae cytolysin promotes activation of mast cell (T helper 2) cytokine production SO CELLULAR MICROBIOLOGY LA English DT Article ID FC-EPSILON-RI; CHONDROITIN SULFATE-E; STRUCTURAL GENE HLYA; EL-TOR; TYROSINE PHOSPHORYLATION; INFLAMMATORY MEDIATORS; NUCLEOTIDE-SEQUENCE; IMMUNE-RESPONSES; FYN KINASE; HEMOLYSIN AB Many strains of Vibrio cholerae produce a cytolysin (VCC) that forms oligomeric transmembrane pores responsible for vacuolization of several cell types in culture. Here we suggest that VCC could contribute to the T helper 2 (Th2) response seen in the natural infection; acting through TLR2, VCC enhances mast cells secretion of IL-4, IL-6 and TNF-alpha by 330-, 290- and 550-fold respectively. Moreover, VCC-induced cytokine production is dependent on increased cytosolic Ca2+ and on the presence of the Src family kinases Lyn and Fyn, known to be required for Fc epsilon RI-dependent activation of mast cells. These findings strongly suggest that VCC has a pro-inflammatory activity promoting a Th2-type immune profile. C1 [Arcidiacono, Diletta; Montecucco, Cesare; de Bernard, Marina] Venetian Inst Mol Med, I-35121 Padua, Italy. [Arcidiacono, Diletta] Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy. [de Bernard, Marina] Univ Padua, Dept Biol, I-35121 Padua, Italy. [Odom, Sandra; Rivera, Juan] NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Frossi, Barbara; Pucillo, Carlo] Univ Udine, Dept Biomed Sci & Technol, I-33100 Udine, Italy. [Frossi, Barbara; Pucillo, Carlo] Univ Udine, MATI Ctr Excellence, I-33100 Udine, Italy. [Paccani, Silvia R.; Baldari, Cosima T.] Univ Siena, Dept Evolutionary Biol, I-53100 Siena, Italy. RP de Bernard, M (reprint author), Venetian Inst Mol Med, Via Orus 2, I-35121 Padua, Italy. EM marina.debernard@unipd.it RI Pucillo, Carlo/A-5515-2008; Arcidiacono, Diletta/B-2557-2017; OI Arcidiacono, Diletta/0000-0002-4417-6513; Pucillo, Carlo/0000-0002-4872-6156 FU Intramural NIH HHS [Z01 AR041155-01]; Associazione Italiana per la Ricerca sul Cancro NR 46 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD APR PY 2008 VL 10 IS 4 BP 899 EP 907 DI 10.1111/j.1462-5822.2007.01092.x PG 9 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 274BY UT WOS:000253978000008 PM 18005391 ER PT J AU Brunet, J Pfaff, AW Abidi, A Unoki, M Nakamura, Y Guinard, M Klein, JP Candolfi, E Mousli, M AF Brunet, Julie Pfaff, Alexander W. Abidi, Ahmed Unoki, Motoko Nakamura, Yusuke Guinard, Marie Klein, Jean-Paul Candolfi, Ermanno Mousli, Marc TI Toxoplasma gondii exploits UHRF1 and induces host cell cycle arrest at G2 to enable its proliferation SO CELLULAR MICROBIOLOGY LA English DT Article ID G1/S TRANSITION; THEILERIA-PARVA; S-PHASE; ICBP90; APOPTOSIS; PROTEIN; GROWTH; EXPRESSION; GENE; ENCEPHALITIS AB Toxoplasma gondii is an obligate intracellular parasite that causes severe disease in humans. It is able to infect all nucleated mammalian cells leading to lifelong persistence of the parasite in the host. Here, we studied the effect of T. gondii infection on host cell proliferation and explored the molecular mechanisms involved in host cell cycle progression. We found that T. gondii induced G1/S transition in host cells in the presence of UHRF1, followed by G2 arrest after cyclin B1 downregulation which is probably the major cause of the arrest. Other molecules at the G2/M checkpoint including p53, p21 and Cdk1 were normally regulated. Interestingly, while parasite proliferation was normal in cells that were in the G2 phase, it was suppressed in G1-arrested cells induced by UHRF1-siRNA, indicating the importance of the G2 phase via UHRF1-induced G1/S transition for T. gondii growth. C1 [Brunet, Julie; Pfaff, Alexander W.; Abidi, Ahmed; Guinard, Marie; Klein, Jean-Paul; Candolfi, Ermanno; Mousli, Marc] Univ Strasbourg 1, Fac Med, Inst Parasitol & Pathol Tropicale Strasbourg, UPRES EA Interact Cellulaires & Mol Hote Paraite, F-67000 Strasbourg, France. [Unoki, Motoko] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Nakamura, Yusuke] Univ Tokyo, Inst Med Sci, Mol Med Lab, Ctr Human Genome, Tokyo, Japan. RP Mousli, M (reprint author), Univ Strasbourg 1, Fac Med, Inst Parasitol & Pathol Tropicale Strasbourg, UPRES EA Interact Cellulaires & Mol Hote Paraite, F-67000 Strasbourg, France. EM marc.mousli@medecine.u-strasbg.fr NR 48 TC 33 Z9 37 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD APR PY 2008 VL 10 IS 4 BP 908 EP 920 DI 10.1111/j.1462-5822.2007.01093.x PG 13 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 274BY UT WOS:000253978000009 PM 18005238 ER PT J AU Morinaga, N Yahiro, K Matsuura, G Moss, J Noda, M AF Morinaga, Naoko Yahiro, Kinnosuke Matsuura, Gen Moss, Joel Noda, Masatoshi TI Subtilase cytotoxin, produced by Shiga-toxigenic Escherichia coli, transiently inhibits protein synthesis of Vero cells via degradation of BiP and induces cell cycle arrest at G1 by downregulation of cyclin D1 SO CELLULAR MICROBIOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; MAMMALIAN-CELLS; RESPONSE PATHWAY; CHAPERONE BIP; TRANSLATION; KINASE; TOXIN; PERK; PHOSPHORYLATION; IDENTIFICATION AB Subtilase cytotoxin (SubAB) is a AB(5) type toxin produced by Shiga-toxigenic Escherichia coli, which exhibits cytotoxicity to Vero cells. SubAB B subunit binds to toxin receptors on the cell surface, whereas the A subunit is a subtilase-like serine protease that specifically cleaves chaperone BiP/Grp78. As noted previously, SubAB caused inhibition of protein synthesis. We now show that the inhibition of protein synthesis was transient and occurred as a result of ER stress induced by cleavage of BiP; it was closely associated with phosphorylation of double-stranded RNA-activated protein kinase-like ER kinase (PERK) and eukaryotic initiation factor-2 alpha (eIF2 alpha). The phosphorylation of PERK and eIF2 alpha was maximal at 30-60 min and then returned to the control level. Protein synthesis after treatment of cells with SubAB was suppressed for 2 h and recovered, followed by induction of stress-inducible C/EBP-homologous protein (CHOP). BiP degradation continued, however, even after protein synthesis recovered. SubAB-treated cells showed cell cycle arrest in G1 phase, which may result from cyclin D1 downregulation caused by both SubAB-induced translational inhibition and continuous prolonged proteasomal degradation. C1 [Morinaga, Naoko; Matsuura, Gen; Noda, Masatoshi] Chiba Univ, Dept Mol Infectiol, Grad Sch Med, Chuo Ku, Chiba 2608670, Japan. [Matsuura, Gen] Chiba Univ, Dept Pediat Surg, Grad Sch Med, Chuo Ku, Chiba 2608670, Japan. [Yahiro, Kinnosuke; Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Morinaga, N (reprint author), Chiba Univ, Dept Mol Infectiol, Grad Sch Med, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. EM nmorinaga@faculty.chiba-u.jp FU Intramural NIH HHS [Z01 HL000659-15] NR 33 TC 22 Z9 22 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD APR PY 2008 VL 10 IS 4 BP 921 EP 929 DI 10.1111/j.1462-5822.2007.01094.x PG 9 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 274BY UT WOS:000253978000010 PM 18005237 ER PT J AU Kuehn, HS Beaven, MA Ma, HT Kim, MS Metcalfe, DD Gilfillan, AM AF Kuehn, Hye Sun Beaven, Michael A. Ma, Hong-Tao Kim, Mi-Sun Metcalfe, Dean D. Gilfillan, Alasdair M. TI Synergistic activation of phospholipases C gamma and C beta: A novel mechanism for PI3K-independent enhancement of Fc epsilon RI-induced mast cell mediator release SO CELLULAR SIGNALLING LA English DT Article DE mast cell; Fc epsilon RI; Gi; signal transduction; phospholipase C; prostaglandin E-2 ID PROTEIN-COUPLED-RECEPTORS; ALLERGIC RESPONSE; PROSTAGLANDIN E-2; TYROSINE KINASE; KIT ACTIVATION; RBL-2H3 CELLS; LINE RBL-2H3; DEGRANULATION; ANTIGEN; PHOSPHORYLATION AB Antigen/IgE-mediated mast cell activation via Fc epsilon RI can be markedly enhanced by the activation of other receptors expressed on mast cells and these receptors may thus contribute to the allergic response in vivo. One such receptor family is the G protein-coupled receptors (GPCRs). Although the signaling cascade linking Fc epsilon RI aggregation to mast cell activation has been extensively investigated, the mechanisms by which GPCRs amplify this response are relatively unknown. To investigate this, we utilized prostaglandin (PG)E-2 based on initial studies demonstrating its greater ability to augment antigen-mediated degranulation in mouse mast cells than other GPCR agonists examined. This enhancement, and the ability of PGE(2) to amplify antigen-induced calcium mobilization, was independent of phosphoinositide 3-kinase but was linked to a pertussis toxin-sensitive synergistic translocation to the membrane of phospholipase (PL)C gamma and PLC beta and to an enhancement of PLC gamma phosphorylation. This "trans-synergistic" activation of PLC beta and gamma, in turn, enhanced production of inositol 1,4,5-trisphosphate, store-operated calcium entry, and activation of protein kinase C (PKC) (alpha and beta). These responses were critical for the promotion of degranulation. This is the first report of synergistic activation between PLC gamma and PLC beta that permits reinforcement of signals for degranulation in mast cells. (C) 2007 Published by Elsevier Inc. C1 [Kuehn, Hye Sun; Kim, Mi-Sun; Metcalfe, Dean D.; Gilfillan, Alasdair M.] NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. [Beaven, Michael A.; Ma, Hong-Tao] NHLBI, NIH, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Gilfillan, AM (reprint author), NIAID, NIH, Lab Allerg Dis, Bldg 10,Room 11C206,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. EM agilfillan@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000965-02] NR 60 TC 38 Z9 39 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD APR PY 2008 VL 20 IS 4 BP 625 EP 636 DI 10.1016/j.cellsig.2007.11.016 PG 12 WC Cell Biology SC Cell Biology GA 284SE UT WOS:000254725300005 PM 18207701 ER PT J AU Hanakawa, T Dimyan, MA Hallett, M AF Hanakawa, Takashi Dimyan, Michael A. Hallett, Mark TI The representation of blinking movement in cingulate motor areas: A functional magnetic resonance imaging study SO CEREBRAL CORTEX LA English DT Article DE bimanual movement; cingulate motor areas; face movement; motor control; neuroimaging ID CORTICAL ACTIVATION PATTERNS; EYE BLINKING; MEDIAL WALL; BIMANUAL COORDINATION; FACIAL NUCLEUS; CORTEX; FMRI; STIMULATION; VOLUNTARY; BRAIN AB Recent anatomical evidence from nonhuman primates indicates that cingulate motor areas (CMAs) play a substantial role in the cortical control of upper facial movement. Using event-related functional magnetic resonance imaging in 10 healthy subjects, we examined brain activity associated with volitional eye closure involving primarily the bilateral orbicularis oculi. The findings were compared with those from bimanual tapping, which should identify medial frontal areas nonsomatotopically or somatotopically related to bilateral movements. In a group-level analysis, the blinking task was associated with rostral cingulate activity more strongly than the bimanual tapping task. By contrast, the bimanual task activated the caudal cingulate zone plus supplementary motor areas. An individual-level analysis indicated that 2 foci of blinking-specific activity were situated in the cingulate or paracingulate sulcus: one close to the genu of the corpus callosum (anterior part of rostral cingulate zone) and the posterior part of rostral cingulate zone. The present data support the notion that direct cortical innervation of the facial subnuclei from the CMAs might control upper face movement in humans, as previously implied in nonhuman primates. The CMAs may contribute to the sparing of upper facial muscles after a stroke involving the lateral precentral motor regions. C1 [Hanakawa, Takashi; Dimyan, Michael A.; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Hanakawa, Takashi] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Cort Funct Disorders, Kodaira, Tokyo 1878502, Japan. RP Hallett, M (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Natl Inst Hlth, Bldg 10 Room 5N226 10 Ctr Dr, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov RI Dimyan, Michael/B-1715-2012; OI Dimyan, Michael/0000-0002-9715-9741 FU Intramural NIH HHS NR 28 TC 15 Z9 17 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2008 VL 18 IS 4 BP 930 EP 937 DI 10.1093/cercor/bhm129 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 274NL UT WOS:000254007900019 PM 17652462 ER PT J AU Kang-Sickel, JCC Fox, DD Nam, TG Jayaraj, K Ball, LM French, JE Klapper, DG Gold, A Nylander-French, LA AF Kang-Sickel, Juei-Chuan C. Fox, Donii D. Nam, Tae-gyu Jayaraj, Karupiah Ball, Louise M. French, John E. Klapper, David G. Gold, Avram Nylander-French, Leena A. TI S-arylcysteine-keratin adducts as biomarkers of human dermal exposure to aromatic hydrocarbons SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID MURINE CLARA CELLS; JET FUEL JP-8; STRATUM-CORNEUM; BENZENE METABOLISM; CYTOCHROMES P450; PROTEIN ADDUCTS; ARENE OXIDES; NAPHTHALENE; HEMOGLOBIN; EXPRESSION AB To measure biomarkers of skin exposure to ubiquitous industrial and environmental aromatic hydrocarbons, we sought to develop an ELISA to quantitate protein adducts of metabolites of benzene and naphthalene in the skin of exposed individuals. We hypothesized that electrophilic arene oxides formed by CYP isoforms expressed in the human skin react with nucleophilic sites on keratin, the most abundant protein in the stratum corneum that is synthesized de novo during keratinocyte maturation and differentiation. The sulthydryl groups of cysteines in the head region of the keratin proteins 1 (K1) and 10 (K10) are likely targets. The following synthetic S-arylcysteines were incorporated into 10-mer head sequences of K1 [GGGRFSS(S-aryl-QGG] and K10 [GGGG(S-aryl-C)GGGGG] to form the predicted immunogenic epitopes for antibody production for ELISA: S-phenylcysteine-K1 (SPK1), S-phenyleysteine-K10 (SPK10), S-(1-naphthyl)cysteine-K1 (1NK1), S-(1-naphthyl)cysteine-K10 (1NK10), S-(2-naphthyl)cysteine-K1 (2NK1), and S-(2-naphthyl)cysteine-K10 (2NK 10). Analysis by ELISA was chosen based on its high throughput and sensitivity, and low cost. The synthetic modified oligopeptides, available in quantity, served both as immunogens and as chemical standards for quantitative ELISA. Polyclonal rabbit antibodies produced against the naphthyl-modified keratins reacted with their respective antigens with threshold sensitivities of 15-31 ng/mL and high specificity over a linear range up to 500 ng/mL. Anti-S-phenylcysteine antibodies were not sufficiently specific or sensitive toward the target antigens for use in ELISA under our experimental conditions. In dermal tape-strip samples collected from 13 individuals exposed to naphthalene-containing jet fuel, naphthyl-conjugated peptides were detected at levels from 0.343 +/- 0.274 to 2.34 +/- 1.61 pmol adduct/mu g keratin but were undetectable in unexposed volunteers. This is the first report of adducts of naphthalene (or of any polycyclic aromatic hydrocarbon) detected in the exposed intact human skin. Quantitation of naphthyl-keratin adducts in the skin of exposed individuals will allow us to investigate the importance of dermal penetration, metabolism, and adduction to keratin and to predict more accurately the contribution of dermal exposure to systemic dose for use in exposure and risk-assessment models. C1 [Kang-Sickel, Juei-Chuan C.; Fox, Donii D.; Nam, Tae-gyu; Jayaraj, Karupiah; Ball, Louise M.; Gold, Avram; Nylander-French, Leena A.] Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Klapper, David G.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [French, John E.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Gold, A (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. EM avram_gold@unc.edu; leena_french@unc.edu FU NIEHS NIH HHS [P42ES05948, ES021134]; PHS HHS [T42/CCT422952, T42/008673] NR 37 TC 9 Z9 9 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X EI 1520-5010 J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 2008 VL 21 IS 4 BP 852 EP 858 DI 10.1021/tx7003773 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 291CC UT WOS:000255168900010 PM 18361511 ER PT J AU Keskin, O Gursoy, A Ma, B Nussinov, R AF Keskin, Ozlem Gursoy, Attila Ma, Buyong Nussinov, Ruth TI Principles of protein-protein interactions: What are the preferred ways for proteins to interact? SO CHEMICAL REVIEWS LA English DT Review ID STRUCTURALLY CONSERVED RESIDUES; NUCLEAR-LOCALIZATION SIGNAL; MAMMALIAN IMPORTIN-ALPHA; P53 TUMOR-SUPPRESSOR; ENERGY HOT-SPOTS; CRYSTAL-STRUCTURE; BINDING-SITES; SACCHAROMYCES-CEREVISIAE; MOLECULAR-INTERACTIONS; AFFINITY MATURATION C1 [Keskin, Ozlem; Gursoy, Attila] Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey. [Keskin, Ozlem; Gursoy, Attila] Koc Univ, Coll Engn, TR-34450 Istanbul, Turkey. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. [Keskin, Ozlem; Nussinov, Ruth] NCI, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Basic Res Program, Frederick, MD 21702 USA. RP Nussinov, R (reprint author), NCI, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Basic Res Program, Bldg 469,Rm 151, Frederick, MD 21702 USA. EM okeskin@ku.edu.tr RI Ma, Buyong/F-9491-2011; Gursoy, Attila/E-9565-2015 OI Ma, Buyong/0000-0002-7383-719X; Gursoy, Attila/0000-0002-2297-2113 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 225 TC 271 Z9 275 U1 10 U2 118 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2665 J9 CHEM REV JI Chem. Rev. PD APR PY 2008 VL 108 IS 4 BP 1225 EP 1244 DI 10.1021/cr040409x PG 20 WC Chemistry, Multidisciplinary SC Chemistry GA 286ON UT WOS:000254855300002 PM 18355092 ER PT J AU Galanter, CA Leibenluft, E AF Galanter, Cathryn A. Leibenluft, Ellen TI Frontiers between attention deficit hyperactivity disorder and bipolar disorder SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID DOPAMINE TRANSPORTER GENE; DEFICIT/HYPERACTIVITY-DISORDER; VAL66MET POLYMORPHISM; NEUROTROPHIC FACTOR; STIMULANT TREATMENT; MANIC SYMPTOMS; MOOD DISORDER; I-DISORDER; PSYCHIATRIC-DISORDERS; SEQUENCE VARIATION AB The co-occurrence of attention deficit hyperactivity disorder (ADHD) and bipolar disorder has received much recent attention in the literature. The authors review the literature examining associations between ADHD and bipolar disorder in children, and data concerning severe irritability in youth with ADHD. This article focuses on (1) population-based studies examining ADHD and bipolar disorder or ADHD and co-occurring irritability, (2) the co-occurrence and prospective relationships of ADHD and bipolar disorder in clinical samples, (3) phenomenology and assessment of bipolar disorder and ADHD, (4) treatment of comorbid ADHD and bipolar disorder, (5) family and genetic studies of ADHD and bipolar disorder, and (6) pathophysiologic comparisons between children with ADHD and irritability and bipolar disorder. We draw on the research to make clinical recommendations and highlight important directions for future research. C1 [Galanter, Cathryn A.] Columbia Univ, New York State Psychiat Inst, Div Child & Adolescent Psychiat, New York, NY 10032 USA. [Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Galanter, CA (reprint author), Columbia Univ, New York State Psychiat Inst, Div Child & Adolescent Psychiat, 1051 Riverside Dr 78, New York, NY 10032 USA. EM cg168@columbia.edu FU NIMH NIH HHS [1 K23 MH071337-3] NR 92 TC 61 Z9 63 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 2008 VL 17 IS 2 BP 325 EP + DI 10.1016/j.chc.2007.11.001 PG 24 WC Psychiatry SC Psychiatry GA 280UH UT WOS:000254451300006 PM 18295149 ER PT J AU Vitiello, B AF Vitiello, Benedetto TI Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID SALTS EXTENDED-RELEASE; RANDOMIZED CLINICAL-TRIAL; DEFICIT/HYPERACTIVITY DISORDER; BLOOD-PRESSURE; SUDDEN-DEATH; DOUBLE-BLIND; STIMULANT MEDICATION; OROS METHYLPHENIDATE; CROSSOVER TRIAL; SHORT-TERM AB The effects of stimulant medications and atomoxetine on physical growth and on cardiovascular function are reviewed in light of the most recent data, with attention to clinical implications and research needs. Although these medications have a favorable benefit/risk profile and do not induce clinically significant changes in growth or cardiovascular function in the majority of cases, careful patient monitoring is needed to identify individuals at risk for negative outcomes. More research is needed to elucidate the mechanism of growth suppression to estimate better the risk for rare but life-threatening events and test the effectiveness of monitoring procedures. C1 NIMH, Child & Adolescent Treatment & Prevent Intervent, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, Div Serv & Intervent Res, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 72 TC 44 Z9 46 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 2008 VL 17 IS 2 BP 459 EP + DI 10.1016/j.chc.2007.11.010 PG 17 WC Psychiatry SC Psychiatry GA 280UH UT WOS:000254451300013 PM 18295156 ER PT J AU Takahashi, Y Strunnikov, A AF Takahashi, Yoshimitsu Strunnikov, Alexander TI In vivo modeling of polysumoylation uncovers targeting of Topoisomerase II to the nucleolus via optimal level of SUMO modification SO CHROMOSOMA LA English DT Article ID NUCLEAR-PORE COMPLEX; SACCHAROMYCES-CEREVISIAE; SUBNUCLEAR LOCALIZATION; PROTEIN SUMOYLATION; DNA TOPOISOMERASES; BUDDING YEAST; GENE-EXPRESSION; GLOBAL ANALYSIS; UBIQUITIN; RANGAP1 AB Conjugation of SUMO to target proteins is an essential eukaryotic regulatory pathway. Multiple potential SUMO substrates were identified among nuclear and chromatin proteins by proteomic approaches. However, the functional roles of SUMO-modified pools of individual proteins remain largely obscure, as only a small fraction of a given target is sumoylated and therefore is experimentally inaccessible. To overcome this technical difficulty in case of Topoisomerase II, we employed constitutive SUMO modification, enabling tracking of modified Top2p, not only biochemically but also cytologically and genetically. Topoisomerase II fused to a critical number of SUMO repeats is concentrated at the specific intranuclear domain, the nucleolus, when more than four SUMO moieties are added, indicating that fused SUMO repeats are biologically active. Further analysis has established that poly-sumoylation of Top2p is required for the stable maintenance of the nucleolar organizer, linking SUMO-mediated targeting to functional maintenance of ribosomal RNA gene cluster. C1 [Takahashi, Yoshimitsu; Strunnikov, Alexander] NICHHD, NIH, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Strunnikov, A (reprint author), NICHHD, 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 [Z99 AI999999, Z01 HD001903-11] NR 45 TC 15 Z9 16 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD APR PY 2008 VL 117 IS 2 BP 189 EP 198 DI 10.1007/s00412-007-0137-1 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 276ZP UT WOS:000254182500009 PM 18046568 ER PT J AU Zhang, C Rexrode, KM van Dam, RM Li, TY Hu, FB AF Zhang, Cuilin Rexrode, Kathryn M. van Dam, Rob M. Li, Tricia Y. Hu, Frank B. TI Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality - Sixteen years of follow-up in US women SO CIRCULATION LA English DT Article DE adiposity; cancer; cardiovascular diseases; mortality; obesity; waist-hip ratio ID BODY-MASS INDEX; WAIST-HIP RATIO; ADIPOSE-TISSUE; HEIGHT RATIO; OLDER WOMEN; CIRCUMFERENCE; FAT; DISEASE; WEIGHT; QUESTIONNAIRE AB Background - Accumulating evidence indicates that abdominal adiposity is positively related to cardiovascular disease (CVD) risk and some other diseases independently of overall adiposity. However, the association of premature death resulting from these diseases with abdominal adiposity has not been widely studied, and findings are inconsistent. Methods and Results - In a prospective cohort study of 44 636 women in the Nurses' Health Study, associations of abdominal adiposity with all-cause and cause-specific mortality were examined. During 16 years of follow-up, 3507 deaths were identified, including 751 cardiovascular deaths and 1748 cancer deaths. After adjustment for body mass index and potential confounders, the relative risks across the lowest to the highest waist circumference quintiles were 1.00, 1.11, 1.17, 1.31, and 1.79 (95% confidence interval [CI], 1.47 to 1.98) for all-cause mortality; 1.00, 1.04, 1.04, 1.28, and 1.99 (95% CI, 1.44 to 2.73) for CVD mortality; and 1.00, 1.18, 1.20, 1.34, and 1.63 (95% CI, 1.32 to 2.01) for cancer mortality (all P < 0.001 for trend). Among normal-weight women (body mass index, 18.5 to <25 kg/m(2)), abdominal obesity was significantly associated with elevated CVD mortality: Relative risk associated with waist circumference >= 88 cm was 3.02 (95% CI, 1.31 to 6.99) and for waist-to-hip ratio >0.88 was 3.45 (95% CI, 2.02 to 6.92). After adjustment for waist circumference, hip circumference was significantly and inversely associated with CVD mortality. Conclusions - Anthropometric measures of abdominal adiposity were strongly and positively associated with all-cause, CVD, and cancer mortality independently of body mass index. Elevated waist circumference was associated with significantly increased CVD mortality even among normal-weight women. C1 [Zhang, Cuilin] NICHHD, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Bethesda, MD 20892 USA. [Rexrode, Kathryn M.] Harvard Univ, Sch Med, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Rexrode, Kathryn M.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [van Dam, Rob M.; Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [van Dam, Rob M.; Hu, Frank B.] Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. [van Dam, Rob M.; Li, Tricia Y.; Hu, Frank B.] Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Hu, Frank B.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Zhang, C (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, 6100 Execut Blvd,Room 7B03,MSC 7510,9000 Rockvill, Bethesda, MD 20892 USA. EM zhangcu@mail.nih.gov; nhbfh@channing.harvard.edu RI van Dam, Rob/F-9674-2010; OI van Dam, Rob/0000-0002-7354-8734; Rexrode, Kathryn/0000-0003-3387-8429 FU Intramural NIH HHS; NCI NIH HHS [CA87969]; NHLBI NIH HHS [HL34594]; NIDDK NIH HHS [DK58845] NR 33 TC 295 Z9 303 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 1 PY 2008 VL 117 IS 13 BP 1658 EP 1667 DI 10.1161/CIRCULATIONAHA.107.739714 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 282OG UT WOS:000254576500006 PM 18362231 ER PT J AU O'Toole, M Legault, H Ramsey, R Wynn, TA Kasaian, MT AF O'Toole, M. Legault, H. Ramsey, R. Wynn, T. A. Kasaian, M. T. TI A novel and sensitive ELISA reveals that the soluble form of IL-13R-alpha 2 is not expressed in plasma of healthy or asthmatic subjects SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE asthma; biomarkers; cytokines ID IL-13 RECEPTOR ALPHA-2; INTERLEUKIN (IL)-13 RESPONSES; SIGNAL-TRANSDUCTION; HUMAN FIBROBLASTS; GENE-EXPRESSION; ALLERGIC-ASTHMA; DECOY RECEPTOR; MURINE MODEL; TNF-ALPHA; CELLS AB Background IL-13 plays a key regulatory role in asthmatic responses and immunity to parasitic infection. In vivo, IL-13R-alpha 2 is a critical modulator of IL-13 bioactivity. When inducibly expressed on the surface of fibroblasts and other cell types under inflammatory conditions, IL-13R-alpha 2 contributes to resolution of IL-13 responses. A soluble form of IL-13R-alpha 2 (sIL-13R-alpha 2) can be detected in murine circulation, and functions as a regulator of IL-13 bioactivity. In humans, sIL-13R-alpha 2 has been more difficult to detect. Recently, novel assay systems have been described to quantitate sIL-13R-alpha 2 in human circulation, and revealed unexpectedly high levels of sIL-13R-alpha 2 in healthy subjects. Objective To verify sIL-13R-alpha 2 quantitation in human plasma samples under stringent conditions of signal verification and false-positive detection. Methods A standard ELISA protocol was evaluated for specificity using false-positive detection reagents. A more stringent ELISA protocol was developed by optimizing the composition of blocking and dilution buffers. Results Using the stringent assay protocol, endogenous sIL-13R-alpha 2 was undetectable in plasma samples from a total of 120 asthmatics and 20 healthy subjects, and in bronchoalveolar lavage fluid from 10 asthmatics and eight healthy subjects undergoing allergen challenge. Conclusion These results underscore the necessity to perform rigorous assay controls in the biological matrix to be tested. Because the soluble form could not be demonstrated, our findings question a role for sIL-13R-alpha 2 in the regulation of IL-13 bioactivity, and highlight the potentially important contribution of the membrane-bound form of IL-13R-alpha 2 in humans. C1 [Kasaian, M. T.] Wyeth Res, Dept Inflammat, Cambridge, MA 02140 USA. [O'Toole, M.; Legault, H.; Ramsey, R.] Wyeth Res, Dept Biol Technol, Cambridge, MA 02140 USA. [Wynn, T. A.] NIAID, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Kasaian, MT (reprint author), Wyeth Res, Dept Inflammat, 200 Cambridge Pk Dr, Cambridge, MA 02140 USA. EM mkasaian@wyeth.com RI Wynn, Thomas/C-2797-2011 FU Intramural NIH HHS [Z01 AI001019-01] NR 42 TC 23 Z9 24 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD APR PY 2008 VL 38 IS 4 BP 594 EP 601 DI 10.1111/j.1365-2222.2007.02921.x PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 275ET UT WOS:000254055400007 PM 18307523 ER PT J AU de Diego, RP Lopez-Granados, E Rivera, J Ferreira, A Fontan, G Bravo, J Rodriguez, MCG Bolland, S AF de Diego, R. Perez Lopez-Granados, E. Rivera, J. Ferreira, A. Fontan, G. Bravo, J. Rodriguez, M. C. Garcia Bolland, S. TI Naturally occurring Bruton's tyrosine kinase mutations have no dominant negative effect in an X-linked agammaglobulinaemia cellular model SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE Bruton's tyrosine kinase; calcium mobilization; DT40 cells; gene therapy; X-linked agammaglobulinaemia ID B-CELL; PHOSPHOLIPASE C-GAMMA-2; XID MICE; IMMUNODEFICIENCY; ACTIVATION; FAMILY; BTK; RECONSTITUTION; EXPRESSION; MONOCYTES AB X-linked agammaglobulinaemia (XLA) is characterized by absence of mature B cells because of mutations in the Bruton's tyrosine kinase (Btk) gene. Btk-deficient early B cell precursors experience a block in their differentiation potentially reversible by the addition of an intact Btk gene. Btk expression was measured in 69 XLA patients with 47 different mutations and normal expression was detected in seven. We characterized these Btk mutant forms functionally by transfection into a lymphoma cell line that lacks endogenous Btk expression (Btk(-/-) DT40 cells) and analysed the calcium flux in response to B cell receptor stimulation. To test whether co-expression of a mutated form could compromise the function of the intact Btk transfection, studies in wild-type (WT) DT40 cells were also performed. Study reveals that none of the seven Btk mutants analysed was able to revert the absence of calcium mobilization upon IgM engagement in Btk(-/-) DT40 cells, as does intact Btk. In addition, calcium mobilization by anti-IgM stimulation in DT40 Btk(+/+) cells was unaffected by co-expression with Btk mutants. These results suggest that gene addition would be feasible not only for patients with XLA and mutations that prevent Btk expression, but for those with expression of a mutant Btk. C1 [de Diego, R. Perez; Rivera, J.; Bravo, J.] Spanish Natl Canc Res Ctr CNIO, Signal Transduct Grp, Madrid 28029, Spain. [de Diego, R. Perez; Lopez-Granados, E.; Ferreira, A.; Fontan, G.; Rodriguez, M. C. Garcia] Univ Hosp La Paz, Immunol Unit, Madrid, Spain. [Bolland, S.] NIAID, NIH, Rockville, MD USA. RP de Diego, RP (reprint author), Spanish Natl Canc Res Ctr CNIO, Signal Transduct Grp, C Melchor Fernandez Almagro 3, Madrid 28029, Spain. EM rperez@cnio.es RI Bravo, Jeronimo/K-9103-2014; Rivera-Torres, Jose/P-2793-2015 OI Bravo, Jeronimo/0000-0001-6695-2846; Rivera-Torres, Jose/0000-0003-0365-9604 NR 38 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2008 VL 152 IS 1 BP 33 EP 38 DI 10.1111/j.1365-2249.2008.03589.x PG 6 WC Immunology SC Immunology GA 270ZC UT WOS:000253757700005 ER PT J AU Goldstein, DS Holmes, C Sato, T Bernson, M Mizrahi, N Imrich, R Carmona, G Sharabi, Y Vortmeyer, AO AF Goldstein, David S. Holmes, Courtney Sato, Takuya Bernson, Miya Mizrahi, Neptune Imrich, Richard Carmona, Gilberto Sharabi, Yehonatan Vortmeyer, Alexander O. TI Central dopamine deficiency in pure autonomic failure SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE pure autonomic failure; Parkinson; fluorodopa; dopamine; DOPAC ID CARDIAC SYMPATHETIC DENERVATION; NEUROGENIC ORTHOSTATIC HYPOTENSION; IDIOPATHIC PARKINSONS-DISEASE; NERVOUS-SYSTEM; LEWY BODIES; CATECHOLS; ASSAY AB Objective Pure autonomic failure (PAF) and Parkinson's disease (PD) share several clinical laboratory abnormalities; however, PAF is not associated with parkinsonism. In this study, we tested the hypothesis that preservation of nigrostriatal dopaminergic innervation explains the absence of motor dysfunction in PAF. Methods Patients with PAF (N = 5) or PD (N = 21) and control subjects (N = 14) had brain 6-[F-18]fluorodopa positron emission tomographic scanning and cerebrospinal fluid catechol measurements. A patient with PAF and another with PD had rapid postmortem striatal, nigral, and sympathetic ganglion sampling, with assays of catechols and tyrosine hydroxylase activity. Results The PAF and PD groups had similarly low mean substantia nigra (SN):occipital (OCC) ratios of 6[-(18)supercript stopF]fluorodopa-derived radioactivity and similarly low cerebrospinal fluid dihydroxyphenylacetic acid and DOPA levels. Only the PD group, however, had low PUT:OCC, caudate:OCC, or PUT:SN ratios. The PAF and PD cases had similarly low SN tissue concentrations of dopamine and tyrosine hydroxylase activity, but the PD patient had tenfold lower PUT dopamine and the PAF patient 15-fold lower myocardial norepinephrine concentrations. Conclusions Surprisingly, PAF and PD entail similarly severe nigral and overall central dopaminergic denervation. There is more severe loss of striatal dopaminergic terminals in PD than in PAF and more severe loss of sympathetic noradrenergic terminals in PAF than in PD. These differences explain the distinctive clinical manifestations of the two Lewy body diseases. Parkinsonism appears to reflect striatal dopamine deficiency rather than loss of nigral dopaminergic neurons per se. C1 [Goldstein, David S.; Holmes, Courtney; Sato, Takuya; Bernson, Miya; Mizrahi, Neptune; Imrich, Richard; Carmona, Gilberto; Sharabi, Yehonatan] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. [Vortmeyer, Alexander O.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Natl Inst Hlth, Bethesda, MD 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 goldsteind@ninds.nih.gov OI Bernson-Leung, Miya/0000-0002-7766-2323 FU Intramural NIH HHS NR 33 TC 16 Z9 17 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD APR PY 2008 VL 18 IS 2 BP 58 EP 65 DI 10.1007/s10286-008-0457-0 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 292PC UT WOS:000255277600002 PM 18363034 ER PT J AU Okazaki, T Jiao, L Chang, P Evans, DB Abbruzzese, JL Li, DH AF Okazaki, Taro Jiao, Li Chang, Ping Evans, Douglas B. Abbruzzese, James L. Li, Donghui TI Single-nucleotide polymorphisms of DNA damage response genes are associated with overall survival in patients with pancreatic cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; CHECKPOINT; ATM; GEMCITABINE; RISK; RADIOSENSITIVITY; ACTIVATION; THERAPY; REPAIR; CHK1 AB Purpose: The goals of this study were to determine if single-nucleotide polymorphisms in DNA damage repair genes and cell cycle regulating genes affect clinical response to combined gemcitabine radiation therapy and the overall survival (OS) of patients with pancreatic cancer. Experimental Design: We evaluated six single-nucleotide polymorphisms of the ATM, ATM and Rad3-related (ATR), CHEK1, and CHEK2 genes in 119 patients with potentially resectable pancreatic cancer who were enrolled in clinical trials at The University of Texas M. D. Anderson Cancer Center from February 1999 toJanuary 2006, with follow-up until February 2007. Patients received neoadjuvant concurrent gemcitabine and radiation therapy with or without gemcitabine-cisplatin induction therapy. Genotypes were determined and tested for associations with OS by Kaplan-Meier estimation, the log-rank test, and Cox regression analysis. P values of <= 0.05 were considered significant. Results: The ATM G60A and CHEK1 G35A genotypes were significant (P < 0.05), and the ATR C340T genotype borderline significantly (P = 0.079) associated with OS. The hazard ratio of CHEV 35AA was 2.01 (95% confidence interval, 1.20-3.37; P = 0.007) compared with CHEV 35GG/GA with adjustments for race, sex, diabetes status, CA19-9 level, and success of tumor resection. A significant combined genotype effect was observed between ATM 60GA/GG, ATR 340CT/CC, and CHEV 35AA with median OS times of 31.0,16.2, and 10.5 months for patients carrying <= 1, 2, and 3 deleterious alleles, respectively (P = 0.004). Conclusions: These observations suggest that polymorphic variations of DNA damage response genes affect clinical response to gemcitabine radiation therapy and OS of patients with resectable pancreatic cancer. C1 [Okazaki, Taro; Chang, Ping; Abbruzzese, James L.; Li, Donghui] Univ Texas Houston, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, Houston, TX 77030 USA. [Evans, Douglas B.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Jiao, Li] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Li, DH (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dli@mdanderson.org FU NCI NIH HHS [P20 CA101936-03, CA16672, P20 CA101936, P20 CA101936-01, P20 CA101936-02, P20 CA101936-04, P20 CA101936-05, P30 CA016672, R01 CA098380, R01 CA098380-02, R01 CA098380-03, R01 CA098380-04, R01 CA098380-05] NR 28 TC 32 Z9 32 U1 0 U2 2 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 APR 1 PY 2008 VL 14 IS 7 BP 2042 EP 2048 DI 10.1158/1078-0432.CCR-07-1520 PG 7 WC Oncology SC Oncology GA 287AC UT WOS:000254887500016 PM 18381943 ER PT J AU Woo, HG Park, ES Cheon, JH Kim, JH Lee, JS Park, BJ Kim, W Park, SC Chung, YJ Kim, BG Yoon, JH Lee, HS Kim, CY Yi, NJ Suh, KS Lee, KU Chu, IS Roskams, T Thorgeirsson, SS Kim, YJ AF Woo, Hyun Goo Park, Eun Sung Cheon, Jae Hee Kim, Ju Han Lee, Ju-Seog Park, Bum Joon Kim, Won Park, Su Cheol Chung, Young Jin Kim, Byeong Gwan Yoon, Jung-Hwan Lee, Hyo-Suk Kim, Chung Yong Yi, Nam-Joon Suh, Kyung-Suk Lee, Kuhn Uk Chu, In-Sun Roskams, Tania Thorgeirsson, Snorri S. Kim, Yoon Jun TI Gene expression-based recurrence prediction of hepatitis B virus-related human hepatocellular carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID ACTIVATED-RECEPTOR-ALPHA; INDEPENDENT PROGNOSTIC MARKER; GROWTH-FACTOR EXPRESSION; CURATIVE RESECTION; CD24 EXPRESSION; RISK-FACTORS; INTRAHEPATIC RECURRENCE; CLINICOPATHOLOGICAL FEATURES; PLASMINOGEN-ACTIVATOR; CLINICAL-SIGNIFICANCE AB Purpose: The poor prognosis of hepatocellular carcinoma (HCC) is, in part, due to the high rate of recurrence even after "curative resection" of tumors. Therefore, it is axiomatic that the development of an effective prognostic prediction model for HCC recurrence after surgery would, at minimum, help to identify in advance those who would most benefit from the treatment, and at best, provide new therapeutic strategies for patients with a high risk of early recurrence. Experimental Design: For the prediction of the recurrence time in patients with HCC, gene expression profiles were generated in 65 HCC patients with hepatitis B infections. Result: Recurrence-associated gene expression signatures successfully discriminated between patients at high-risk and low-risk of early recurrence (P = 1.9 x 10(-6), log-rank test). To test the consistency and robustness of the recurrence signature, we validated its prognostic power in an independent HCC microarray data set. CD24 was identified as a putative biomarker for the prediction of early recurrence. Genetic network analysis suggested that SP1 and peroxisome proliferator-activated receptor-alpha might have regulatory roles for the early recurrence of HCC. Conclusion: We have identified a gene expression signature that effectively predicted early recurrence of HCC independent of microarray platforms and cohorts, and provided novel biological insights into the mechanisms of tumor recurrence. C1 [Park, Bum Joon; Kim, Won; Park, Su Cheol; Chung, Young Jin; Kim, Byeong Gwan; Yoon, Jung-Hwan; Lee, Hyo-Suk; Kim, Chung Yong; Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Park, Bum Joon; Kim, Won; Park, Su Cheol; Chung, Young Jin; Kim, Byeong Gwan; Yoon, Jung-Hwan; Lee, Hyo-Suk; Kim, Chung Yong; Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul, South Korea. [Lee, Ju-Seog] Seoul Natl Univ Biomed Informat, Seoul, South Korea. [Yi, Nam-Joon; Suh, Kyung-Suk; Lee, Kuhn Uk] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea. [Cheon, Jae Hee] Yonsei Univ, Coll Med, Dept Internal Med, Inst Gastroenterol, Seoul, South Korea. [Woo, Hyun Goo; Chu, In-Sun] Korea Res Inst Biosci & Biotechnol, Korea Bioinformat Ctr, Taejon, South Korea. [Woo, Hyun Goo; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Park, Eun Sung] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Div Canc Med, Houston, TX USA. [Roskams, Tania] Univ Leuven, Dept Morphol & Mol Pathol, Louvain, Belgium. RP Kim, YJ (reprint author), Seoul Natl Univ Hosp, Dept Internal Med, 28 Yongon Dong, Seoul 110744, South Korea. EM yoonjun@snu.ac.kr RI Park, Byung-Joo/E-5438-2011; Kim, Ju Han/E-5983-2012; Kim, Yoon Jun/J-2746-2012; Kim, Byeong Gwan/J-5395-2012; Yoon, Jung Hwan/J-5563-2012; Lee, Hyo-Suk/J-5618-2012; Yi, Nam-Joon/J-5574-2012; Suh, Kyung-Suk/J-5508-2012; Cheon, Jae Hee/B-4523-2015 OI Park, Byung-Joo/0000-0003-4630-4942; Cheon, Jae Hee/0000-0002-2282-8904 NR 48 TC 77 Z9 81 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2008 VL 14 IS 7 BP 2056 EP 2064 DI 10.1158/1078-0432.CCR-07-1473 PG 9 WC Oncology SC Oncology GA 287AC UT WOS:000254887500018 PM 18381945 ER PT J AU Timmers, HJLM Pacak, K Bertherat, J Lenders, JWM Duet, M Eisenhofer, G Stratakis, CA Niccoli-Sire, P Huy, PTB Burnichon, N Gimenez-Roqueplo, AP AF Timmers, Henri J. L. M. Pacak, Karel Bertherat, Jerome Lenders, Jacques W. M. Duet, Michele Eisenhofer, Graeme Stratakis, Constantine A. Niccoli-Sire, Patricia Huy, Patrice Tran Ba Burnichon, Nelly Gimenez-Roqueplo, Anne-Paule TI Mutations associated with succinate dehydrogenase D-related malignant paragangliomas SO CLINICAL ENDOCRINOLOGY LA English DT Article ID HEREDITARY PARAGANGLIOMA; FAMILIAL PARAGANGLIOMA; CLINICAL PRESENTATION; GENE-MUTATIONS; SDHD GENE; PHEOCHROMOCYTOMA; FEATURES; DISTINCT; BENIGN AB Objective Hereditary paraganglioma (PGL) syndromes result from germline mutations in genes encoding subunits B, C and D of the mitochondrial enzyme succinate dehydrogenase (SDHB, SDHC and SDHD). SDHB-related PGLs are known in particular for their high malignant potential. Recently, however, malignant PGLs were also reported among a small minority of Dutch carriers of the SDHD founder mutation D92Y. The aim of the study was to investigate which SDHD mutations are associated with malignant PGL. Design Case histories; collaborative study between referral centres in France, the USA, and the Netherlands. Patients Six unrelated patients with metastatic PGLs of either sympathetic or parasympathetic origin. Measurements Assessment of SDHD mutations underlying malignant PGL. Results Germline SDHD mutations underlying metastatic PGL were G148D, Y114X, L85X, W43X, D92Y, and IVS2+5G -> A. Conclusion Our findings indicate that malignant SDHD-related PGL is associated with several mutations besides D92Y. C1 [Timmers, Henri J. L. M.; Pacak, Karel] NICHHD, Reprod Biol & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6525 ED Nijmegen, Netherlands. Grp Hosp Cochin, AP HP, Serv Endocrinol, F-75010 Paris, France. [Bertherat, Jerome] INSERM, Unite 567, F-75010 Paris, France. [Bertherat, Jerome] CNRS, UMR8140, Inst Cochin, F-75010 Paris, France. [Bertherat, Jerome] Univ Paris 05, F-75010 Paris, France. [Duet, Michele] Hop Lariboisiere, AP HP, Dept Nucl Med, F-75010 Paris, France. [Duet, Michele] Univ Paris 07, F-75221 Paris 05, France. [Eisenhofer, Graeme] Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, Bethesda, MD USA. [Niccoli-Sire, Patricia] CHU Timone, Serv Endocrinol, Marseille, France. [Huy, Patrice Tran Ba] Hop Lariboisiere, AP HP, Dept Otorhinolaryngol, F-75010 Paris, France. [Burnichon, Nelly; Gimenez-Roqueplo, Anne-Paule] Hop Europeen Georges Pompidou, AP HP, Serv Genet, F-75015 Paris, France. [Gimenez-Roqueplo, Anne-Paule] Univ Paris 05, Fac Med, F-75005 Paris, France. [Gimenez-Roqueplo, Anne-Paule] INSERM, Unite 772, F-75005 Paris, France. [Gimenez-Roqueplo, Anne-Paule] Coll France, F-75005 Paris, France. RP Timmers, HJLM (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, CRC, 10 Ctr Dr Bldg 10,RM 1-E 3140, Bethesda, MD 20892 USA. EM h.timmers@endo.umcn.nl RI Lenders, J.W.M./L-4487-2015 FU Intramural NIH HHS NR 22 TC 30 Z9 33 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD APR PY 2008 VL 68 IS 4 BP 561 EP 566 DI 10.1111/j.1365-2265.2007.03086.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 274BW UT WOS:000253977800010 PM 17973943 ER PT J AU McDermott, WG Boissan, M Lacombe, ML Steeg, PS Horak, CE AF McDermott, William G. Boissan, Mathieu Lacombe, Marie-Lise Steeg, Patricia S. Horak, Christine E. TI Nm23-H1 homologs suppress tumor cell motility and anchorage independent growth SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE anchorage independent growth; metastasis; metastasis suppressor gene; motility; Nm23 ID NUCLEOSIDE DIPHOSPHATE KINASE; BREAST-CARCINOMA CELLS; INHIBITORY-ACTIVITY; MELANOMA-CELLS; CANCER CELLS; IN-VITRO; ADENOCARCINOMA CELLS; GENE-EXPRESSION; ALPHA-ISOFORM; METASTASIS AB Nm23-H1 suppresses metastasis, as well as in vitro cell motility, invasion and anchorage independent growth, in a variety of cancer models. Eight human homologs of Nm23 have been identified that share 26-88% identity with the prototype Nm23-H1. Here, we examine the potential of its homologs, -H2, DR-, -H4 and -H5, to inhibit in vitro correlates of metastasis in two highly metastatic human cell lines, MDA-MB-435 and MDA-MB-231. The metastatic cells were transfected with mammalian expression constructs containing the genes encoding for Nm23-H1, -H2, DR-, -H4 and -H5 and the resultant transfectants were analyzed by Boyden chamber motility and soft agar colonization assays. Nm23-H1 suppressed motility by 3.3-and 1.5-fold in MDA-MB-435 and MDA-MB-231 cells, respectively and inhibited anchorage independent growth in soft agar by 2.9-and 1.9-fold, respectively. None of the-H1 homologs were capable of suppressing motility in MDA-MB-435 cells, but in MDA-MB-231 cells, -H2 inhibited motility by 3-fold upon overexpression. When anchorage independent growth was assessed, -H2, -H4 and -H5 suppressed growth from 1.2-to 2.0-fold in both cell lines. Given their ability to suppress anchorage independent growth, Nm23-H1 homologs -H2, -H4 and -H5 may have some capacity to suppress metastasis. Motility suppression appears to be cell context dependent, but sequence disparities between -H1/H2 and the other family members may reveal regions critical for this inhibitory phenotype. Similarly, sequence differences between DR-Nm23 and its homologs may be important for anchorage independent growth suppression. C1 [McDermott, William G.; Steeg, Patricia S.; Horak, Christine E.] NCI, Mol Pharmacol Lab, Womens canc Sect, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Boissan, Mathieu; Lacombe, Marie-Lise] INSERM, U680, F-75012 Paris, France. [Boissan, Mathieu; Lacombe, Marie-Lise] Univ Paris 06, Fac Med, UMRS680, F-75005 Paris, France. RP Horak, CE (reprint author), NCI, Mol Pharmacol Lab, Womens canc Sect, Ctr Canc Res,NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM horakc@mail.nih.gov FU Intramural NIH HHS NR 41 TC 22 Z9 25 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD APR PY 2008 VL 25 IS 2 BP 131 EP 138 DI 10.1007/s10585-007-9128-0 PG 8 WC Oncology SC Oncology GA 279NA UT WOS:000254360700004 PM 18058029 ER PT J AU De Sanjose, S Benavente, Y Vajdic, CM Engels, EA Morton, LM Bracci, PM Spinelli, JJ Zheng, TZ Zhang, YW Franceschi, S Talamini, R Holly, EA Grulich, AE Cerhan, JR Hartge, P Cozen, W Boffetta, P Brennan, P Maynadie, M Cocco, P Bosch, R Foretova, L Staines, A Becker, N Nieters, A AF De Sanjose, Silvia Benavente, Yolanda Vajdic, Claire M. Engels, Eric A. Morton, Lindsay M. Bracci, Paige M. Spinelli, John J. Zheng, Tongzhang Zhang, Yawei Franceschi, Silvia Talamini, Renato Holly, Elizabeth A. Grulich, Andrew E. Cerhan, James R. Hartge, Patricia Cozen, Wendy Boffetta, Paolo Brennan, Paul Maynadie, Marc Cocco, Pierluigi Bosch, Ramon Foretova, Lenka Staines, Anthony Becker, Nikolaus Nieters, Alexandra TI Hepatitis C and non-Hodgkin lymphoma among 4784 cases and 6269 controls from the international lymphoma epidemiology consortium SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID VIRUS CORE PROTEIN; B-CELL LYMPHOMA; MIXED CRYOGLOBULINEMIA; LOW-GRADE; INFECTION; RISK; CLASSIFICATION; LYMPHOCYTES; INTERLYMPH; NEOPLASMS AB Background & Aims: increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the risk of non-Hodgkin's lymphoma (NHL) subtypes after HCV infection. Methods: The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded. Results: HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40 -2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44-4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.682.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14-5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65-1.60). Conclusions: These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma). C1 [De Sanjose, Silvia; Benavente, Yolanda] Hosp Llobregat, Ctr Invest Biomed Red Epidemiol & Salud Publ, Inst Invest Biomed Bellvitge, Catalan Inst Oncol,Unit Ingect & Canc, Barcelona 08907, Spain. [Vajdic, Claire M.; Grulich, Andrew E.] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. [Engels, Eric A.; Morton, Lindsay M.; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Spinelli, John J.] British Columbia Canc Agcy, Canc Control Res Program, Vancouver, BC V5Z 4E6, Canada. [Zheng, Tongzhang; Zhang, Yawei] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Franceschi, Silvia; Boffetta, Paolo; Brennan, Paul] Int Agcy Res Canc, Genet Epidemiol Grp, F-69372 Lyon, France. [Talamini, Renato] Aviano Canc Ctr, Epidemiol & Biostat Unit, I-33081 Aviano, Italy. [Cerhan, James R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Maynadie, Marc] Fac Med Dijon, Registre Hemopathies Malignes Cote Or, Dijon, France. [Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Cagliari, Italy. [Bosch, Ramon] Hosp Tortosa Verge de la Cinta, Dept Pathol, Tortosa, Spain. [Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic. [Staines, Anthony] Publ Hlth Univ Coll, Dept Publ Hlth, Dublin, Ireland. [Becker, Nikolaus; Nieters, Alexandra] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. RP De Sanjose, S (reprint author), Hosp Llobregat, Ctr Invest Biomed Red Epidemiol & Salud Publ, Inst Invest Biomed Bellvitge, Catalan Inst Oncol,Unit Ingect & Canc, Gran Via Km 2-7, Barcelona 08907, Spain. EM s.sanjose@iconcologia.net RI Spinelli, John/B-6210-2013; de Sanjose Llongueras, Silvia/H-6339-2014; Morton, Lindsay/B-5234-2015; Bosch Princep, Ramon/F-4229-2016; Benavente, Yolanda/H-9810-2014; OI Morton, Lindsay/0000-0001-9767-2310; Bosch Princep, Ramon/0000-0003-4104-5515; Vajdic, Claire/0000-0002-3612-8298; Cerhan, James/0000-0002-7482-178X; Staines, Anthony/0000-0001-9161-1357 FU Intramural NIH HHS [ZIA CP010170-13]; NCI NIH HHS [CA89745, CA104682, CA51086, CA62006, CA87014, PC65064, PC67008, PC67009, PC67010, PC71105]; PHS HHS [A45614]; Associazione Italiana per la Ricerca sul Cancro NR 52 TC 125 Z9 133 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2008 VL 6 IS 4 BP 451 EP 458 DI 10.1016/j.cgh.2008.02.011 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 286LA UT WOS:000254846200016 PM 18387498 ER PT J AU Peters, LM Fridell, RA Boger, ET Agustin, TBS Madeo, AC Griffith, AJ Friedman, TB Morell, RJ AF Peters, L. M. Fridell, R. A. Boger, E. T. Agustin, T. B. San Madeo, A. C. Griffith, A. J. Friedman, T. B. Morell, R. J. TI A locus for autosomal dominant progressive non-syndromic hearing loss, DFNA27, is on chromosome 4q12-13.1 SO CLINICAL GENETICS LA English DT Article DE DFNA27; genetic linkage; inner ear; non-syndromic hearing loss ID DEAFNESS; IMPAIRMENT; MUTATIONS; GENE AB We ascertained a large North American family, LMG2, segregating progressive, non-syndromic, sensorineural hearing loss. A genome-wide scan identified significant evidence for linkage (maximum logarithm of the odds (LOD) score = 4.67 at theta = 0 for D4S398) to markers in a 5.7-cM interval on chromosome 4q12-13.1. The DFNA27 interval spans 8.85 Mb and includes at least 61 predicted and 8 known genes. We sequenced eight genes and excluded them as candidates for the DFNA27 gene. C1 [Peters, L. M.; Boger, E. T.; Madeo, A. C.; Griffith, A. J.; Friedman, T. B.; Morell, R. J.] Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. [Fridell, R. A.] Bristol Myers Squibb Co, Dept Virol, Wallingford, CT 06492 USA. [Agustin, T. B. San] Natl Inst Disabil & Rehabilitat Res, Off Special Educ & Rehabilitat Serv, US Dept Educ, Landover, MD USA. RP Morell, RJ (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court,Rm2A19, Rockville, MD 20850 USA. EM morellr@nidcd.nih.gov RI Madeo, Anne/K-2880-2012; OI Morell, Robert/0000-0003-1537-7356 FU Intramural NIH HHS NR 18 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD APR PY 2008 VL 73 IS 4 BP 367 EP 372 DI 10.1111/j.1399-0004.2008.00966.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 274BX UT WOS:000253977900012 PM 18279434 ER PT J AU Amorosi, S D'Armiento, M Calcagno, G Russo, I Adriani, M Christiano, AM Weiner, L Brissette, JL Pignata, C AF Amorosi, S. D'Armiento, M. Calcagno, G. Russo, I. Adriani, M. Christiano, A. M. Weiner, L. Brissette, J. L. Pignata, C. TI FOXN1 homozygous mutation associated with anencephaly and severe neural tube defect in human athymic Nude/SCID fetus SO CLINICAL GENETICS LA English DT Article DE anencephaly; FOXN1; neural tube defects; SCID; thymic aplasia ID TRANSCRIPTION FACTORS; GENE-EXPRESSION; CHOROID-PLEXUS; FORK HEAD; MOUSE; IMMUNODEFICIENCY; DIFFERENTIATION; PHENOTYPE; GENOTYPE; ALOPECIA AB The forkhead, Fox, gene family comprises a diverse group of 'winged-helix' transcription factors that play important roles in development, metabolism, cancer and aging. Recently, several forkhead genes have been demonstrated to play critical roles in lymphocyte development and effector functions. Alterations of the FOXN1 gene in both mice and humans result in a severe combined immunodeficiency caused by an intrinsic defect of the thymus associated with congenital alopecia (Nude/severe combined immunodeficiency phenotype). FOXN1 is a member of the class of proteins involved in the development and differentiation of the central nervous system. We identified a human fetus homozygous for a mutation in FOXN1 gene who lacked the thymus and also had abnormal skin, anencephaly and spina bifida. Moreover, we found that FOXN1 gene is expressed in mouse developing choroid plexus. These observations suggest that FOXN1 may be involved in neurulation in humans. C1 [Amorosi, S.; Russo, I.; Pignata, C.] Univ Naples Federico 2, Dept Pediat, Immunol Unit, I-80131 Naples, Italy. [D'Armiento, M.] Univ Naples Federico 2, Dept Biomorphol Sci, I-80131 Naples, Italy. [Calcagno, G.] Univ Naples Federico 2, Dept Biochem & CEINGE Scarl, I-80131 Naples, Italy. [Adriani, M.] NHGRI, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. [Christiano, A. M.] Columbia Univ, Dept Dermatol, New York, NY 10027 USA. [Christiano, A. M.] Columbia Univ, Dept Genet & Dev, New York, NY USA. [Weiner, L.; Brissette, J. L.] Massachusetts Gen Hosp, Harvard Med Sch, Cutaneous Biol Res Ctr, Dept Dermatol, Charlestown, MA USA. RP Pignata, C (reprint author), Univ Naples Federico 2, Dept Pediat, Immunol Unit, Via S Pansini 5, I-80131 Naples, Italy. EM pignata@unina.it RI Adriani, Marsilio/F-2553-2013; Pignata, Claudio/O-2466-2013; OI Pignata, Claudio/0000-0003-1568-9843; Calcagno, Giuseppe/0000-0003-4680-1535 FU NIAMS NIH HHS [R01 AR045284, R01 AR045284-10, R01 AR055218, R01 AR055218-01A1] NR 28 TC 27 Z9 28 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD APR PY 2008 VL 73 IS 4 BP 380 EP 384 DI 10.1111/j.1399-0004.2008.00977.x PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 274BX UT WOS:000253977900014 PM 18339010 ER PT J AU Woolery, M Bisanz, A Lyons, HF Gaido, L Yenulevich, M Fulton, S McMillan, SC AF Woolery, Myra Bisanz, Annette Lyons, Hannah F. Gaido, Lindsay Yenulevich, Mary Fulton, Stephanie McMillan, Susan C. TI Putting evidence into Practice (R): Evidence-based interventions for the prevention and management of constipation in patients with cancer SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Review ID CHRONIC NONCANCER PAIN; RELEASE ORAL MORPHINE; TRANSDERMAL FENTANYL; OPIOID ANTAGONISTS; BOWEL DYSFUNCTION; DIETARY FIBER; DOUBLE-BLIND; LACTULOSE; EFFICACY; CHILDREN AB Constipation is a major source of distress for patients with cancer, significantly affecting quality of life. It can be secondary to disease sequelae, side effects of treatment, or preexisting conditions. It often is unrecognized, underassessed, and ineffectively managed. Nurses play a key role in the prevention and management of constipation and need evidence-based interventions. This article summarizes the existing research evidence for constipation interventions and identifies gaps, Many of the strategies have been evaluated in nononcology populations; researchers should evaluate their effectiveness in oncology populations. C1 [Woolery, Myra] Natl Inst Hlth, Bethesda, MD 20892 USA. [Woolery, Myra] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. [Bisanz, Annette] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lyons, Hannah F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gaido, Lindsay; Fulton, Stephanie] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Yenulevich, Mary] Dana Farber Canc Inst, Boston, MA 02115 USA. [McMillan, Susan C.] Univ S Florida, Coll Nursing, Tampa, FL USA. RP Woolery, M (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA. EM mwoolery@cc.nih.gov NR 82 TC 22 Z9 24 U1 0 U2 4 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD APR PY 2008 VL 12 IS 2 BP 317 EP 337 DI 10.1188/08.CJON.317-337 PG 21 WC Oncology; Nursing SC Oncology; Nursing GA 299DN UT WOS:000255736100018 PM 18390467 ER PT J AU Ragert, P Vandermeeren, Y Camus, M Cohen, LG AF Ragert, Patrick Vandermeeren, Yves Camus, Mickael Cohen, Leonardo G. TI Improvement of spatial tactile acuity by transcranial direct current stimulation SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE transcranial direct current stimulation (tDCS); tactile acuity; somatosensory cortex; grating orientation task (GOT); perceptual; cortical plasticity ID SOMATOSENSORY-EVOKED POTENTIALS; HUMAN MOTOR CORTEX; MAGNETIC STIMULATION; GRATING ORIENTATION; DIGITAL ANESTHESIA; BRAIN-STIMULATION; DC STIMULATION; PRECISION GRIP; FORCE CONTROL; HUMANS AB Objective: Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) has been successfully used to induce polarity-specific excitability changes in the brain. However, it is still unknown if anodal tDCS (tDCS nodal) applied to the primary somatosensory cortex (S1) can lead to behavioral changes in performance of tactile discriminative tasks. Methods: Using an accurate tactile discrimination task (grating orientation task: GOT) we tested the hypothesis that application of 1 mA of tDCS(anodal) (current density at the electrodes of 0.04 mA/cm(2)) over the left S1 can lead to an improved tactile spatial acuity in the contralateral index-finger (IF). Results: Performance in the GOT task with the contralateral IF but not with the ipsilateral IF was enhanced for about 40 min after a 20 min application of tDCS(anodal) in the absence of changes with sham stimulation. Conclusions: These results provide the first evidence that tDCS(anodal) over S1 improves performance in a complex somatosensory task beyond the period of stimulation. Significance: The ability to induce performance improvement in the somatosensory domain with tDCS applied over SI could be used to promote functional recovery in patients with diminished tactile perception. (c) Published by Elsevier Ireland Ltd on behalf of International Federation of Clinical Neurophysiology. C1 [Ragert, Patrick; Vandermeeren, Yves; Camus, Mickael; Cohen, Leonardo G.] NINDS, HCPS, NIH, Bethesda, MD 20817 USA. RP Cohen, LG (reprint author), NINDS, HCPS, NIH, Bethesda, MD 20817 USA. EM cohenl@ninds.nih.gov FU Intramural NIH HHS [Z01 NS002978-09] NR 47 TC 62 Z9 66 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD APR PY 2008 VL 119 IS 4 BP 805 EP 811 DI 10.1016/j.clinph.2007.12.001 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 290GA UT WOS:000255110100009 PM 18203660 ER PT J AU McCann, DJ AF McCann, D. J. TI Potential of buprenorphine/naltrexone in treating polydrug addiction and co-occurring psychiatric disorders SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID KAPPA-OPIOID RECEPTOR; CONDITIONED PLACE PREFERENCE; REDUCES ALCOHOL-DRINKING; NOCICEPTIN/ORPHANIN FQ; COCAINE DEPENDENCE; SEEKING BEHAVIOR; PREFERRING RATS; REINSTATEMENT; ETHANOL; ACTIVATION AB In recent years, we have seen regulatory approval being given for several new pharmacotherapies in the treatment of drug addiction disorders. Within the United States, the most noteworthy development has been the approval of buprenorphine in the treatment of opioid dependence, and its availability for prescribing in an office-based setting has resulted in thousands of additional patients going into treatment. Although approved medications for the treatment of cocaine and methamphetamine dependence are still lacking, the National Institute on Drug Abuse has devoted substantial effort toward meeting these clinical needs.(1) Recent studies of modafinil for the treatment of cocaine dependence have been especially encouraging. Looking to the future, the looming challenge is polydrug addiction, a situation that is often complicated by co-occurring psychiatric disorders. As we strive to address the needs of these complicated patients, studies of buprenorphine/naltrexone may hold the key to a major advance. C1 Natl Inst Drug Abuse, NIH, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD USA. RP McCann, DJ (reprint author), Natl Inst Drug Abuse, NIH, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD USA. EM dmccann@nih.gov NR 36 TC 26 Z9 26 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 2008 VL 83 IS 4 BP 627 EP 630 DI 10.1038/sj.clpt.6100503 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 279BM UT WOS:000254330000026 PM 18212797 ER PT J AU Gozalo, AS Cheng, LI St Claire, ME Ward, JM Elkins, WR AF Gozalo, Alfonso S. Cheng, Lily I. St Claire, Marisa E. Ward, Jerrold M. Elkins, William R. TI Pathology of captive moustached tamarins (Saguinus mystax) SO COMPARATIVE MEDICINE LA English DT Article ID COLITIS-CYSTICA-PROFUNDA; HEPATITIS-A VIRUS; CALLITRICHID IGM NEPHROPATHY; MYOCARDIAL FIBROSIS; MARMOSETS; CARDIOMYOPATHY; HYPERTENSION; HYPERTROPHY; CHIMPANZEES; ENTERITIS AB The pathology of 33 moustached tamarins (Saguinus mystax) previously used in hepatitis A and GB virus studies is reported. Chronic lesions in colon, heart, and kidney were common in the monkeys and appeared not to be due to the experimental exposures. Colitis cystica profunda (CCP), a disease that affects humans and is characterized by the presence of mucin-filled epithelial downgrowths and cysts in the colonic submucosa, was found in 24 of the 33 (72.7%) tamarins. Interstitial myocardial fibrosis was present in 22 (66.6%) animals, and various degrees of membranoproliferative glomerulonephritis occurred in 28 (84.8%) monkeys. In addition, 28 (84.8%) tamarins demonstrated diffuse hepatocellular vacuolation with mild lymphoplasmacytic infiltrates, possibly as a result of the experimental infections, and peliosis hepatis occurred in 7 (21.2%) animals. The etiology of CCP is unknown, and no reliable animal models are available because most cases in animals are reported only sporadically. Myocardial fibrosis in tamarins has not been reported previously, and all current animal models require experimental manipulation of the animal to mimic the human disease. The results from this study suggest that captive S. mystax has high incidence of spontaneous CCP, myocardial fibrosis, and membranoproliferative glomerulonephritis. This species may be a spontaneous animal model for pathogenesis and experimental therapy studies of the analogous human diseases. C1 [Gozalo, Alfonso S.; Cheng, Lily I.; Ward, Jerrold M.; Elkins, William R.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Gozalo, Alfonso S.; Cheng, Lily I.; Ward, Jerrold M.] SoBran Inc, Bethesda, MD USA. [St Claire, Marisa E.] NIAID, Div Clin Res, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. EM gozaloa@niaid.nih.gov FU Intramural NIH HHS NR 40 TC 9 Z9 10 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD APR PY 2008 VL 58 IS 2 BP 188 EP 195 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 298GN UT WOS:000255674500010 PM 18524178 ER PT J AU Itahashi, M Higaki, S Sugahara, D Sugioka, K Deai, T Takao, K Hayashi, K Shimomura, Y AF Itahashi, Motoki Higaki, Shiro Sugahara, Daisuke Sugioka, Koji Deai, Tatsunori Takao, Kazumasa Hayashi, Kozaburo Shimomura, Yoshikazu TI A new acyclovir analogue inhibits murine herpetic keratitis SO CORNEA LA English DT Article DE A-5021; acyclovir; herpes simplex virus type 1; herpetic; keratitis; murine model ID SIMPLEX-VIRUS TYPE-1; VARICELLA-ZOSTER-VIRUS; ANTIVIRAL ACTIVITY; CELL-CULTURE; PENCICLOVIR; FAMCICLOVIR; THERAPY; PRODRUG; A-5021; RESISTANCE AB Purpose: To determine the efficacy of A-5021, a new analogue of acyclovir, on murine herpetic keratitis. Methods: Herpes simplex virus type 1 (strain CHR3) was inoculated onto bilateral scarified BALB/c corneas. Clinical scores on the corneas treated with A-5021 eyedrops were compared with those obtained from the treatment with 3% acyclovir eye ointment by slit lamp microscopy. Virus titers of the trigeminal ganglia and eyeballs were quantitated on Vero cell monolayers. Mice treated with saline or a white petroleum jelly were used as controls. Results: A-5021 eyedrops significantly suppressed both corneal epithelial and stromal lesions at all concentrations used. Clinical scores on the epithelium and stroma treated with 0.1% A-5021 were equivalent to those with 3% acyclovir treatment. When compared with the non-drug-treated control mice, virus titers in the eyeballs and trigerminal ganglia in A-5021- and acyclovir-treated mice were significantly less than those in controls. Conclusions: A-5021 eyedrops, which are easily applied onto the affected cornea, ameliorated clinical scores and suppressed virus growth. It is a promising alternative treatment of herpetic keratitis. C1 [Itahashi, Motoki; Higaki, Shiro; Sugahara, Daisuke; Sugioka, Koji; Deai, Tatsunori; Shimomura, Yoshikazu] Kinki Univ, Sch Med, Dept Ophthalmol, Sayama, Osaka 5898511, Japan. [Takao, Kazumasa] Ms Sci Corp, Kobe, Hyogo, Japan. [Hayashi, Kozaburo] NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shimomura, Y (reprint author), Kinki Univ, Sch Med, Dept Ophthalmol, 377-2 Ohno Higashi, Sayama, Osaka 5898511, Japan. EM yoshis@med.kindai.ac.jp NR 25 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD APR PY 2008 VL 27 IS 3 BP 334 EP 338 PG 5 WC Ophthalmology SC Ophthalmology GA 285RP UT WOS:000254794200016 PM 18362663 ER PT J AU Su, JW Li, XM Cui, XZ Li, Y Fitz, Y Hsu, L Mani, H Quezado, M Eichacker, PQ AF Su, Junwu Li, Xuemei Cui, Xizhong Li, Yan Fitz, Yvonne Hsu, Lewis Mani, Haresh Quezado, Martha Eichacker, Peter Q. TI Ethyl pyruvate decreased early nuclear factor-kappa B levels but worsened survival in lipopolysaccharide-challenged mice SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 103rd International Conference of the American-Thoracic-Society CY MAY 18-23, 2007 CL San Francisco, CA SP Amer Thorac Soc DE ethyl pyruvate; lipopolysaccharide; sepsis; treatment ID ACUTE-RENAL-FAILURE; HEMORRHAGIC-SHOCK; ISCHEMIA-REPERFUSION; PROLONGS SURVIVAL; ENDOTOXIC-SHOCK; MURINE MODEL; LIVER-INJURY; IN-VITRO; SEPSIS; RESUSCITATION AB Background. Ethyl pyruvate (EP) treatment inhibits nuclear factor (NF)-kappa B-mediated inflammation and has been considered for sepsis. However, NF-kappa B is also protective, and its inhibition may have adverse effects. Methods: We studied EP in lipopolysaccharide-challenged mice and systematically analyzed its efficacy in published sepsis models. Results: After I ipopolysaccha ride, compared with placebo (n = 68), each of six doses of EP (0.01-100 mg/kg, n = 204) increased the hazards ratio of death. Although these increases were individually not significant (p = .13 to.37), when combined, they were (log mean +/- SEM, 0.26 +/- 0.13; p = .01). At 3 and 9 hrs after challenge, lipopolysaccharide increased lung NF-kappa B and 12 serum cytokines (p <= .05 vs. phosp hate-buffered saline challenge, except for interleukin-4 at 9 hrs). With lipopolysaccharide, although EP (100 mg/kg) decreased NF-kappa B and 11 of 12 cytokines at 3 hrs, it increased NF-kappa B and 11 of 12 cytokines at 9 hrs in patterns that differed (p <=.05) across time points. In 14 published comparisons, EP's effects on the odds ratio of death varied (I-2 = 85% [95% confidence interval, 74-91%], p < .0001), decreasing it significantly in five of the studies but not the other nine. In three of the latter, it increased time to death. Conclusion. Although EP has had promising effects in some preclinical sepsis models, it has not in others, and in the present model, it worsened outcome. Based on the complex role NF-kappa B has regulating both maladaptive and protective host responses, further defining factors that influence EP's effects is important if this agent is considered for patients with or at risk of sepsis. C1 [Su, Junwu; Li, Xuemei; Cui, Xizhong; Li, Yan; Eichacker, Peter Q.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. [Su, Junwu] Capital Med Univ, Anzhen Univ, Surg Dept Pediat Cardiol, Beijing, Peoples R China. [Li, Xuemei] Peking Union Med Coll, Dept Nephrol, Beijing, Peoples R China. [Hsu, Lewis] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Mani, Haresh; Quezado, Martha] Natl Inst Hlth, Dept Pathol, Dept Crit Care Med, Bethesda, MD USA. RP Su, JW (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. EM peichacker@cc.nih.gov FU Intramural NIH HHS NR 46 TC 16 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2008 VL 36 IS 4 BP 1059 EP 1067 DI 10.1097/CCM.0B013E318164403B PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 284BJ UT WOS:000254679900004 PM 18176313 ER PT J AU O'Grady, NP Barie, PS Bartlett, JG Bleck, T Carroll, K Kalil, AC Linden, P Maki, DG Nierman, D Pasculle, W Masur, H AF O'Grady, Naomi P. Barie, Philip S. Bartlett, John G. Bleck, Thomas Carroll, Karen Kalil, Andre C. Linden, Peter Maki, Dennis G. Nierman, David Pasculle, William Masur, Henry TI Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America SO CRITICAL CARE MEDICINE LA English DT Review DE fever; intensive care unit; critical illness; blood cultures; catheter infection; pneumonia; colitis; sinusitis; surgical site infection; nosocomial infection; temperature measurement; urinary tract infection ID VENTILATOR-ASSOCIATED PNEUMONIA; BLOOD-STREAM INFECTION; DIFFICILE-ASSOCIATED-DIARRHEA; CATHETER-RELATED INFECTION; URINARY-TRACT-INFECTIONS; SYMPTOMATIC VENOUS THROMBOEMBOLISM; INADEQUATE ANTIMICROBIAL TREATMENT; VANCOMYCIN-RESISTANT ENTEROCOCCUS; NOSOCOMIAL MAXILLARY SINUSITIS; NEUROLEPTIC MALIGNANT SYNDROME AB Objective: To update the practice parameters for the evaluation of adult patients who develop a new fever in the intensive care unit, for the purpose of guiding clinical practice. Participants: A task force of 11 experts in the disciplines related to critical care medicine and infectious diseases was convened from the membership of the Society of Critical Care Medicine and the Infectious Diseases Society of America. Specialties represented included critical care medicine, surgery, internal medicine, infectious diseases, neurology, and laboratory medicine/microbiology. Evidence: The task force members provided personal experience and determined the published literature (MEDLINE articles, textbooks, etc.) from which consensus was obtained. Published literature was reviewed and classified into one of four categories, according to study design and scientific value. Consensus Process: The task force met twice in person, several times by teleconference, and held multiple e-mail discussions during a 2-yr period to identify the pertinent literature and arrive at consensus recommendations. Consideration was given to the relationship between the weight of scientific evidence and the strength of the recommendation. Draft documents were composed and debated by the task force until consensus was reached by nominal group process. Conclusions: The panel concluded that, because fever can have many infectious and noninfectious etiologies, a new fever in a patient in the intensive care unit should trigger a careful clinical assessment rather than automatic orders for laboratory and radiologic tests. A cost-conscious approach to obtaining cultures and imaging studies should be undertaken if indicated after a clinical evaluation. The goal of such an approach is to determine, in a directed manner, whether infection is present so that additional testing can be avoided and therapeutic decisions can be made. C1 [O'Grady, Naomi P.; Masur, Henry] NIH, Bethesda, MD 20892 USA. [Barie, Philip S.] Weill Cornell Med Coll, New York, NY USA. [Bartlett, John G.; Carroll, Karen] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Bleck, Thomas] Northwestern Univ, Chicago, IL 60611 USA. [Kalil, Andre C.] Univ Nebraska, Omaha, NE 68182 USA. [Linden, Peter; Pasculle, William] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Maki, Dennis G.] Univ Wisconsin, Sch Med, Madison, WI USA. [Nierman, David] Mt Sinai Hosp, New York, NY 10029 USA. RP O'Grady, NP (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM nogrady@mail.cc.nih.gov OI Bleck, Thomas/0000-0002-8267-9787 NR 202 TC 179 Z9 198 U1 4 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2008 VL 36 IS 4 BP 1330 EP 1349 DI 10.1097/CCM.0b013e318169eda9 PG 20 WC Critical Care Medicine SC General & Internal Medicine GA 284BJ UT WOS:000254679900039 PM 18379262 ER PT J AU Zaborskis, A Petronyte, G Sumskas, L Kuzman, M Iannotti, RJ AF Zaborskis, Apolinaras Petronyte, Gintare Sumskas, Linas Kuzman, Marina Iannotti, Ronald J. TI Body image and weight control among adolescents in Lithuania, Croatia, and the United States in the context of global obesity SO CROATIAN MEDICAL JOURNAL LA English DT Article ID SELF-REPORTED HEIGHT; FEMALE ADOLESCENTS; YOUNG ADOLESCENTS; CONTROL BEHAVIORS; OVERWEIGHT; GIRLS; DISSATISFACTION; VALIDITY; BOYS; RELIABILITY AB Aim To compare body image and weight control behavior among adolescents in Lithuania, Croatia, and the United States (US), the countries with striking contrasts in the prevalence of overweight among adolescents. Method The study was carried out according to the methodology of the Health Behavior in School-aged Children collaborative survey. Nationally-representative samples of students, aged 13 and 15, were surveyed in Lithuania (3778 respondents), Croatia (2946 respondents), and the US (3546 respondents) in the 2001/2002 school year. Results In all three countries, girls perceived themselves as being "too fat" more frequently than boys (37.0% vs 19.7%, P<0.001, z test). The prevalence of this perception increased with age among girls (32.7% vs 41.1%, P<0.001, z test) and decreased among boys (21.4% vs 17.9%, P = 0.005, z test). Lithuanian adolescents were least likely to perceive themselves as "too fat;" this perception was significantly more frequent in Croatia and the US (24.2%,27.5%, and 34.3%, respectively; P<0.001, chi(2) test). With the exception of 15-year-old Lithuanian boys, in all respondents the proportion of adolescents with body mass index (BMI) >= 85th percentile who perceived themselves as "too fat" was significantly higher (up to 3.13 times among 15-year-old US girls) than the proportion of adolescents with BMI <= 15th percentile who perceived themselves as "too thin." The highest proportion of overweight boys and girls on a diet or doing something else to lose weight was found in the US. Boys in Lithuania were most likely to be satisfied with their weight regardless of their weight status. Conclusion Perceived body image and weight control behavior differ among adolescents in Lithuania, Croatia, and the US. Cross-cultural, age, and sex influences moderate body image and weight control behavior in underweight and overweight adolescents. C1 [Zaborskis, Apolinaras; Petronyte, Gintare; Sumskas, Linas] Univ Med, Inst Biomed Res Kaunas, LT-50009 Kaunas, Lithuania. [Kuzman, Marina] Croatian Natl Inst Publ Hlth, Zagreb, Croatia. [Iannotti, Ronald J.] NICHHD, Bethesda, MD 20892 USA. RP Zaborskis, A (reprint author), Univ Med, Inst Biomed Res Kaunas, Eiveniu Str 4, LT-50009 Kaunas, Lithuania. EM socped@kmu.lt NR 28 TC 11 Z9 13 U1 1 U2 5 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-9504 J9 CROAT MED J JI Croat. Med. J. PD APR PY 2008 VL 49 IS 2 BP 233 EP 242 DI 10.3325/cmj.2008.2.233 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 302GX UT WOS:000255957900013 PM 18461679 ER PT J AU Cruz, AA Togias, A AF Cruz, Alvaro A. Togias, Alkis TI Upper airways reactions to cold air SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Review ID NASAL RESPIRATORY MUCOSA; MAST-CELL ACTIVATION; DRY AIR; INFLAMMATORY MEDIATORS; HUMIDIFY AIR; HYPEROSMOLAR SOLUTIONS; CAPSAICIN RECEPTOR; ALLERGIC RHINITIS; HISTAMINE-RELEASE; FINE-STRUCTURE AB Cold air-induced rhinitis is a common complaint of individuals with chronic allergic or nonallergic rhinitis and those with no chronic nasal disease. It is characterized by rhinorrhea, nasal congestion, and nasal burning that appear within minutes of exposure to cold air and dissipate soon after exposure is terminated. The symptoms of cold-air rhinitis are reproduced experimentally with nasal cold-air provocation. This procedure has shown that nasal mast cell activation and sensory nerve stimulation are associated with the development of nasal symptoms. Sensory nerve activation generates a cholinergic reflex that leads to rhinorrhea; therefore, anticholinergic agents are highly effective in treating cold-air rhinitis. Experimental data suggest that individuals with nasal cold-air sensitivity may have reduced ability to compensate for the water loss that occurs during exposure to cold air. Therefore, the symptoms of cold air-induced rhinitis may reflect the activation of compensatory mechanisms to restore mucosal homeostasis. C1 [Cruz, Alvaro A.; Togias, Alkis] NIH, Div Allergy Immunol & Transplantat, Bethesda, MD 20817 USA. RP Togias, A (reprint author), NIH, Div Allergy Immunol & Transplantat, 6610 Rockledge Dr,Room 3065, Bethesda, MD 20817 USA. EM togias@niaid.nih.gov RI Cruz, Alvaro/I-1676-2012 OI Cruz, Alvaro/0000-0002-7403-3871 NR 54 TC 10 Z9 11 U1 0 U2 3 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD APR PY 2008 VL 8 IS 2 BP 111 EP 117 DI 10.1007/s11882-008-0020-z PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 286DY UT WOS:000254827200005 PM 18417052 ER PT J AU Pechhold, K Koczwara, K AF Pechhold, Klaus Koczwara, Kerstin TI Immunomodulation of Autoimmune Diabetes by Dendritic Cells SO CURRENT DIABETES REPORTS LA English DT Article ID DOUBLE KNOCKOUT MICE; CD8(+) T-CELLS; NOD MICE; CROSS-PRESENTATION; DNA VACCINATION; TRANSGENIC MICE; TNF-ALPHA; IN-VIVO; MOUSE; ANTIGEN AB The biology and properties of dendritic cells (DCs) have been intensely studied in the research areas of infectious diseases, tumor immunology, and vaccine development. This unique subset of immune cells has recently also moved to the center of interest for basic and clinical research in autoimmunity, owing not only to the extraordinary importance of DCs in the initiation and sustenance of adaptive immune responses, but also to more recent discoveries about their profound ability to control and downregulate ongoing T-cell responses. We review current progress of using DCs in mice for induction and propagation of autoimmune T-cell responses and their therapeutic potential to dampen or even stop beta-cell-specific autoimmunity. Finally, we offer our perspective on how basic research progress in DC technology, mostly from mouse models, may translate into emerging diagnostic and therapeutic applications for human type 1 diabetes. C1 [Pechhold, Klaus] NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Pechhold, K (reprint author), NIDDKD, Diabet Branch, NIH, 10 Ctr Dr,Bldg 10-CRC,Room 5W-5888, Bethesda, MD 20892 USA. EM KlausP@intra.NIDDK.NIH.gov FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. NR 50 TC 5 Z9 5 U1 1 U2 1 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD APR PY 2008 VL 8 IS 2 BP 107 EP 113 DI 10.1007/s11892-008-0020-3 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 375FU UT WOS:000261100300005 PM 18445352 ER PT J AU Qasba, PK Ramakrishnan, B Boeggeman, E AF Qasba, Pradman K. Ramakrishnan, Boopathy Boeggeman, Elizabeth TI Structure and Function of beta-1,4-Galactosyltransferase SO CURRENT DRUG TARGETS LA English DT Review ID FIBROBLAST-GROWTH-FACTOR; GOLGI RETENTION SIGNAL; ALPHA-LACTALBUMIN LA; BETA-R BETA; CELL-SURFACE; LACTOSE SYNTHETASE; CRYSTAL-STRUCTURE; N-ACETYLGLUCOSAMINE; BOVINE BETA-1,4-GALACTOSYLTRANSFERASE; CONGENITAL DISORDERS AB Beta-1,4-galactosylransferase (beta 4Gal-T1) participates in the synthesis of Gal beta 1-4-GlcNAc-disaccharide unit of glycoconjugates. It is a trans-Golgi glycosyltransferase (Glyco-T) with a type II membrane protein topology, a short N-terminal cytoplasmic domain, a membrane-spanning region, as well as a stem and a C-terminal catalytic domain facing the trans-Golgi-lumen. Its hydrophobic membrane-spanning region, like that of other Glyco-T, has a shorter length compared to plasma membrane proteins, an important feature for its retention in the trans-Golgi. The catalytic domain has two flexible loops, a long and a small one. The primary metal binding site is located at the N-terminal hinge region of the long flexible loop. Upon binding of metal ion and sugar-nucleotide, the flexible loops undergo a marked conformational change, from an open to a closed conformation. Conformational change simultaneously creates at the C-terminal region of the flexible loop an oligosaccharide acceptor binding site that did not exist before. The loop acts as a lid covering the bound donor substrate. After completion of the transfer of the glycosyl unit to the acceptor, the saccharide product is ejected; the loop reverts to its native conformation to release the remaining nucleotide moiety. The conformational change in beta 4Gal-T1 also creates the binding site for a mammary gland-specific protein, lactalbumin ( LA), which changes the acceptor specificity of the enzyme toward glucose to synthesize lactose during lactation. The specificity of the sugar donor is generally determined by a few residues in the sugar-nucleotide binding pocket of Glyco-T, conserved among the family members from different species. Mutation of these residues has allowed us to design new and novel glycosyltransferases, with broader or requisite donor and acceptor specificities, and to synthesize specific complex carbohydrates as well as specific inhibitors for these enzymes. C1 [Qasba, Pradman K.; Ramakrishnan, Boopathy; Boeggeman, Elizabeth] NCI, CCR, Struct Glycobiol Sect, Nanobiol Program, Frederick, MD 21702 USA. [Ramakrishnan, Boopathy; Boeggeman, Elizabeth] SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, CCR, Struct Glycobiol Sect, Nanobiol Program, Bldg 469,Room 221, Frederick, MD 21702 USA. EM qasba@helix.nih.gov FU Intramural NIH HHS [Z01 BC009304-12, Z01 BC010041-11, Z01 BC010742-01, Z99 CA999999]; PHS HHS [N01-C0-12400] NR 115 TC 56 Z9 56 U1 2 U2 18 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD APR PY 2008 VL 9 IS 4 BP 292 EP 309 DI 10.2174/138945008783954943 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 283RI UT WOS:000254653800005 PM 18393823 ER PT J AU Laky, K Fowkes, BJ AF Laky, Karen Fowkes, B. J. TI Notch signaling in CD4 and CD8 T cell development SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID IN-VIVO; PRE-TCR; THYMOCYTE DEVELOPMENT; LINEAGE COMMITMENT; GATA3 EXPRESSION; GENE-EXPRESSION; ALPHA-BETA; CROSS-TALK; RBP-J; DIFFERENTIATION AB Because Notch often acts in concert with other signaling pathways, it is able to regulate a diverse set of biological processes in a cell-context dependent manner. In lymphocytes, Notch is essential for specifying the T cell fate and for promoting early stages of T cell differentiation. At later stages of development, Notch signaling is proposed to direct CD4 versus CD8 T lineage commitment. This hypothesis has been challenged by recent studies of conditional Presenilin-deficient mice showing that Notch promotes the selection and maturation of CD4 and CD8 T cells by potentiating TCR signal transduction in immature thymocytes. While similar conclusions have not been reported with conditional mutation of other downstream mediators of Notch activation, it appears that functional inhibition may not have been achieved at a comparable stage of development and/or analogous issues have not been addressed. The differences also question whether in thymocytes Notch signals only through the canonical pathway. Further study of conditional mutants, signaling intermediates, and transcriptional regulators are needed to elucidate how Notch facilitates TCR signaling in generating mature T cells. C1 [Laky, Karen; Fowkes, B. J.] NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Laky, K (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. EM klaky@niaid.nih.gov; bfowlkes@nih.gov FU Intramural NIH HHS [Z01 AI000486-21] NR 71 TC 29 Z9 29 U1 2 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2008 VL 20 IS 2 BP 197 EP 202 DI 10.1016/j.coi.2008.03.004 PG 6 WC Immunology SC Immunology GA 323FB UT WOS:000257428600011 PM 18434124 ER PT J AU Moutsopoulos, NM Wen, J Wahl, SM AF Moutsopoulos, Niki M. Wen, Jie Wahl, Sharon M. TI TGF-beta and tumors - an ill-fated alliance SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID GROWTH-FACTOR-BETA; SQUAMOUS-CELL CARCINOMA; REGULATORY T-CELLS; TRANSCRIPTION FACTOR FOXP3; LYMPH-NODE; CANCER; IMMUNITY; HEAD; MICROENVIRONMENT; INTERLEUKIN-21 AB Mechanisms of host defense can form an unwitting alliance with tumor cells to promote tumor progression, invasion, and dissemination to distant sites. By secreting TGF-beta, an immunoregulatory molecule designated for both promoting inflammation and dampening immune responses, the tumor tricks the host into supporting its expansion and survival. TGF-beta not only recruits leukocytes to secrete chemokines, growth factors, cytokines, and proteases in support of a tumor-friendly niche but also in a context-specific manner, incapacitates the emergent immune response. As a profound immunosuppressant, TGF-beta, both directly and through the generation of regulatory T cells, blunts immune surveillance, favoring tumor escape. Collectively, the ability of the tumor to hijack these host defense pathways can tip the balance in favor of the tumor. C1 [Moutsopoulos, Niki M.; Wen, Jie; Wahl, Sharon M.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM smwahl@dir.nidcr.nih.gov FU Intramural NIH HHS [Z01 DE000046-37] NR 50 TC 33 Z9 34 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2008 VL 20 IS 2 BP 234 EP 240 DI 10.1016/j.coi.2008.04.003 PG 7 WC Immunology SC Immunology GA 323FB UT WOS:000257428600017 PM 18486463 ER PT J AU Nygaard, TK Deleo, FR Voyich, JM AF Nygaard, Tyler K. DeLeo, Frank R. Voyich, Jovanka M. TI Community-associated methicillin-resistant Staphylococcus aureus skin infections: advances toward identifying the key virulence factors SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE CA-MRSA; skin infection; virulence ID PANTON-VALENTINE LEUKOCIDIN; UNITED-STATES; IN-VITRO; EXPRESSION; STRAINS; CLONE; DETERMINANTS; EPIDEMIC; INSIGHTS; USA300 AB Purpose of review In recent years there has been an increase in the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in healthy individuals, the cause of which is largely unknown. CA-MRSA primarily causes skin and soft-tissue infections but certain strains are also associated with unusually severe pathology. The purpose of this review is to provide a critical analysis of our current knowledge of virulence factors contributing to skin and soft-tissue infections caused by CA-MRSA. Recent findings Isolates classified as pulsed-field gel electrophoresis type USA300 have emerged as the predominant CA-MRSA genotype and in most geographic areas account for 97% or more of CA-MRSA infections. Recent key studies, such as those reporting the complete genome sequence of USA300, and the discovery of cytolytic peptides that contribute significantly to CA-MRSA virulence, lead the way for future investigations. Summary Although we have only a cursory understanding of the molecular mechanisms of CA-MRSA virulence, studies using clinically relevant CA-MRSA isolates are beginning to identify virulence determinants specific to this pathogen. Identifying CA-MRSA virulence determinants and the concerted regulation of these factors will foster development of vaccines and therapeutics designed to control CA-MRSA skin infections. C1 [Nygaard, Tyler K.; Voyich, Jovanka M.] Montana State Univ, Vet Mol Biol Dept, Bozeman, MT 59718 USA. [DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Voyich, JM (reprint author), Montana State Univ, Vet Mol Biol Dept, Mol Biosci Bldg,960 Technol Blvd, Bozeman, MT 59718 USA. EM jovanka@montana.edu OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS; NCRR NIH HHS [P20RR020185, P20RR16455-07] NR 40 TC 27 Z9 28 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD APR PY 2008 VL 21 IS 2 BP 147 EP 152 PG 6 WC Infectious Diseases SC Infectious Diseases GA 281AB UT WOS:000254467200006 PM 18317037 ER PT J AU Nechaev, S Severinov, K AF Nechaev, Sergei Severinov, Konstantin TI The elusive object of desire - Interactions of bacteriophages and their hosts SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID PROVIDES ACQUIRED-RESISTANCE; ESCHERICHIA-COLI; RNA-POLYMERASE; STREPTOCOCCUS-THERMOPHILUS; INHIBITOR IPI; DNA REPEATS; LAMBDA DNA; CRISPR; PHAGE; REPLICATION AB Bacteria and their viruses (phages) are locked in an evolutionary contest, with each side producing constantly changing mechanisms of attack and defense that are aimed to increase the odds of survival. As a result, phages play central roles in a great variety of genetic processes and increase the rate of evolutionary change of the bacterial host, which could ultimately work to the benefit of the host in a long run. C1 [Nechaev, Sergei] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Severinov, Konstantin] Rutgers State Univ, Dept Mol Biol & Biochem, Waksman Inst, Piscataway, NJ 08854 USA. [Severinov, Konstantin] Russian Acad Sci, Inst Mol Genet, Moscow 123182, Russia. [Severinov, Konstantin] Russian Acad Sci, Inst Gene Biol, Moscow 117312, Russia. RP Nechaev, S (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Room D434,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM nechaevs@niehs.nih.gov; severik@waksman.rutgers.edu RI Severinov, Konstantin/C-8545-2016 FU Intramural NIH HHS [Z99 ES999999]; NIGMS NIH HHS [R01 GM059295, R01 GM059295-01, R01 GM59295] NR 45 TC 29 Z9 31 U1 1 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD APR PY 2008 VL 11 IS 2 BP 186 EP 193 DI 10.1016/j.mib.2008.02.009 PG 8 WC Microbiology SC Microbiology GA 300EH UT WOS:000255806600017 PM 18400552 ER PT J AU Hikosaka, O Bromberg-Martin, E Hong, S Matsumoto, M AF Hikosaka, Okihide Bromberg-Martin, Ethan Hong, Simon Matsumoto, Masayuki TI New insights on the subcortical representation of reward SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID MIDBRAIN DOPAMINE NEURONS; PRIMATE CAUDATE-NUCLEUS; VENTRAL TEGMENTAL AREA; BASAL GANGLIA; LATERAL HABENULA; DORSAL STRIATUM; EYE-MOVEMENTS; AMYGDALA; MODULATION; SEROTONIN AB Reward information is represented by many subcortical areas and neuron types, which constitute a complex network. Its output is usually mediated by the basal ganglia where behaviors leading to rewards are disinhibited and behaviors leading to no reward are suppressed. Midbrain dopamine neurons modulate these basal ganglia neurons differentially using signals related to reward-prediction error. Recent studies suggest that other types of subcortical neurons assist, instruct, or work in parallel with dopamine neurons. Such reward-related neurons are found in the areas which have been associated with stress, pain, mood, emotion, memory, and arousal. These results suggest that reward needs to be understood in a larger framework of animal behavior. C1 [Hikosaka, Okihide; Bromberg-Martin, Ethan; Hong, Simon; Matsumoto, Masayuki] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Bromberg-Martin, Ethan] Brown Univ, Dept Neurosci, Brown NIH Grad Partnership Program, Providence, RI 02906 USA. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr,Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. EM oh@lsr.nei.nih.gov FU National Eye Institute FX This work was supported by the intramural research program of the National Eye Institute. NR 50 TC 79 Z9 81 U1 0 U2 14 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 2008 VL 18 IS 2 BP 203 EP 208 DI 10.1016/j.conb.2008.07.002 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 363PO UT WOS:000260279400014 PM 18674617 ER PT J AU Nelson, KB Chang, T AF Nelson, Karin B. Chang, Taeun TI Is cerebral palsy preventable? SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE cerebral palsy; congenital hemiparesis; electronic fetal monitoring in labor; prematurity; quadriplegia; spastic diplegia ID PERINATAL ARTERIAL STROKE; HYPOXIC-ISCHEMIC ENCEPHALOPATHY; BIRTH-WEIGHT INFANTS; INHALED NITRIC-OXIDE; GENETIC POLYMORPHISMS; PREMATURE-INFANTS; PRETERM DELIVERY; CHILDREN BORN; HYPOTHERMIA; PREVALENCE AB Purpose of review To use evidence of good medical quality to update information on strategies for prevention of cerebral palsy, and on the success of these preventive efforts to date. Recent findings Causes of cerebral palsy, and therefore promising approaches to prevention, differ by gestational age group and by clinical subtype. Neuroimaging and neuropathology indicate the importance of white matter disorders and of ischemic stroke in cerebral palsy; birth asphyxia, congenital malformations, placental pathology, and genetic variants also contribute to cerebral palsy risk. Multiplicity of risk factors markedly increases risk. Recent studies indicate that mild hypothermia lessens cerebral palsy risk in term infants with moderate neonatal encephalopathy, and the possibility that administration of magnesium sulphate to women in preterm labor may aid in primary prevention of cerebral palsy in very preterm infants. Summary Past efforts to prevent cerebral palsy have not had the benefits sought, but recent results provide new hope and new challenges. C1 [Nelson, Karin B.] NINDS, NIH, Bethesda, MD 20892 USA. [Nelson, Karin B.; Chang, Taeun] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. RP Nelson, KB (reprint author), NINDS, NIH, Bldg 31,Room 8A03, Bethesda, MD 20892 USA. EM knelson@helix.nih.gov FU Intramural NIH HHS NR 70 TC 24 Z9 25 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2008 VL 21 IS 2 BP 129 EP 135 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 288FW UT WOS:000254972600004 PM 18317269 ER PT J AU Schwartz, DR Sack, MN AF Schwartz, Daniel R. Sack, Michael N. TI Targeting the mitochondria to augment myocardial protection SO CURRENT OPINION IN PHARMACOLOGY LA English DT Review ID ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; SKELETAL-MUSCLE; IN-VIVO; ISCHEMIA-REPERFUSION; CALORIE RESTRICTION; CARDIAC ISCHEMIA; RECEPTOR-GAMMA; ELECTRON-TRANSPORT; PPAR-ALPHA AB The dynamic regulation of the structure, function and turnover of mitochondria is recognized as an immutable control node maintaining cellular integrity and homeostasis. The term 'mitohormesis' has recently been coined to describe the adaptive reprogramming of mitochondrial biology in response to low levels of metabolic substrate deprivation to augment subsequent mitochondrial and cellular tolerance to biological stress. Disruption of these regulatory programs gives rise to cardiovascular and neurodegenerative diseases, and augmentation or fine-tuning of these programs may ameliorate mitochondrial and global cellular stress tolerance. This is in part via the regulation of reactive oxygen species, calcium homeostasis, and in response to caloric restriction, the capacity to augment DNA repair. The objective of this manuscript is to briefly review these regulatory programs and to postulate novel therapeutic approaches with the primary goal of modulating mitochondria to enhance tolerance to cardiac ischemic stress. C1 [Schwartz, Daniel R.; Sack, Michael N.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Sack, MN (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sackm@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 63 TC 30 Z9 31 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD APR PY 2008 VL 8 IS 2 BP 160 EP 165 DI 10.1016/j.coph.2007.12.008 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 287QO UT WOS:000254931800009 PM 18243790 ER EF